PMID- 10879060
TI  - [Antithrombotic therapy for stroke prevention in patients with atrial
      fibrillation].
AB  - Atrial fibrillation(AF) is a common arrhythmia that is an important independent
      risk factor for stroke. The overall risk of stroke in AF patients averages about
      5%/y, but with wide variation depending on the presence of coexistent
      thromboembolic risk factors, which include increasing age, history of
      hypertension, previous stroke or transient ischemic attack(TIA), and diabetes. AF
      patients with prior stroke or TIA are at highest risk(about 12%/y). Adjusted-dose
      warfarin(target INR 2.0-3.0) is highly efficacious for preventing stroke in AF
      patients, and is safe for selected patients. Aspirin has a modest effect on
      reducing stroke. Warfarin is recommended for high-risk AF patients who can safely
      receive it. Aspirin may be indicated for those with a low stroke risk and for
      those who cannot receive warfarin.

PMID- 10879061
TI  - [Recent progress of midkine research on cancer].
AB  - Midkine is a heparin-binding growth factor, implicated in various biological
      phenomena such as neuronal survival and differentiation, tissue remodeling and
      carcinogenesis. Together with pleiotrophin, midkine constitutes a family that is
      distinct from other heparin-binding growth factors. In this review, I will
      briefly describe biochemical and biological characteristics of midkine and then
      focus on its biological significance in cancer. The most intriguing feature of
      midkine in cancer is its augmented expression in advanced tumors at very high
      frequency in non-tissue specific manner. In addition, its high expression is also
      detected in precancerous lesions. Midkine exerts carcinogenesis-related
      activities, including transforming, anti-apoptotic, angiogenic and fibrinolytic
      ones. These data provide a possibility of clinical application of midkine. Serum
      midkine level can be a useful tumor marker. Gene therapy using its promoter
      region and therapeutic strategy choosing midkine as a molecular target are worth
      challenging.

PMID- 10879062
TI  - [End-of-life care in the elderly].

PMID- 10879063
TI  - [Regulatory mechanisms of calcium signals].

PMID- 10879064
TI  - [The concept of dementia].

PMID- 10879065
TI  - [Acute myelogenous leukemia in elderly patients].

PMID- 10879066
TI  - [Development of new therapeutics based on the concept "death and regeneration"].

PMID- 10879067
TI  - [Advance in clinical studies on atherosclerosis].
AB  - Atherosclerosis leading to coronary heart disease and cerebrovascular disorders
      is the most serious cause of death in the industrialized societies. For the last
      two decades, great advances have been made in understanding the pathogenesis of
      those disorders by studies based on molecular and cell biology. These findings
      have been confirmed by several randomized clinical trials. In this article, the
      current status of treatment and prevention of atherosclerosis will be reviewed
      and discussed.

PMID- 10879068
TI  - [Alzheimer's disease: basic aspects].
AB  - The deposition of amyloid beta peptides (A beta) in one of the pathological
      hallmarks of Alzheimer's disease (AD). A beta are composed of 40-42 amino acid
      peptides that are proteolytically cleaved from beta amyloid precursor proteins
      (beta APP). The deposition as diffuse plaques of a species of A beta ending at
      the 42nd residue residue (A beta 42) is one of the earliest pathological changes
      of AD. Importantly, mutations in beta APP genes located in positions flanking the
      A beta sequences have been shown to cosegregate with the clinical manifestations
      of AD in a subset of familial AD (FAD) pedigrees. Moreover, mutations in
      presenilin (PS) 1 and 2, novel polytropic membrane proteins that were identified
      as causative molecules for the majority of early onset FAD, also increase the
      secretion and deposition of A beta 42. These results support the notion that A
      beta 42 plays a key role in the pathogenesis of AD. Recently, it was suggested
      that PS1 is a coactivator of gamma-cleavage of beta APP as well as gamma-like
      cleavage of Notch protein which plays an essential role in morphogenesis and
      development. In addition, the pathogenic role of tau in neuronal death is
      highlighted based on the identification of mutations in tau gene in a dominantly
      inherited neurodegenerative dementia FTDP-17. These novel findings regarding the
      protein aggregates and causative genes for AD and related disorders will
      facilitate our understanding of the pathogenesis of AD, as well as development of
      therapeutic strategies against it.

PMID- 10879069
TI  - [A new interventional strategy for Alzheimer's disease by Japanese herbal
      medicine].
AB  - A Japanese herbal medicine termed "Kami-Umtan-To (KUT)" was first described in
      Japanese literature in 1626, KUT consists of 13 different herbs, and it has been
      used for a long time in the treatment of a variety of neuropsychiatric problems
      including neurosis and insomnia. Recently, Yabe et al. have demonstrated that KUT
      increased both choline acetyltransferase (ChAT) and nerve growth factor at the
      protein and mRNA levels in cultured rat brain cells. Moreover, the same research
      group has reported that KUT improved mean latency on passive avoidance test in
      both basal for brain lesioned and aged rats. KUT significantly improved the
      survival rate, and increased the number of ChAT-positive neurons in aged rats.
      Here, we report a 12-month open clinical trial of KUT and combination of
      estrogen, vitamin E and NSAID to aim at slowing down the progression of
      Alzheimer's disease (AD). Twenty AD patients (MMSE score: 18.6 +/- 5.8) received
      extracts from original KUT herbs, and 7AD patients (MMSE score: 21.3 +/- 2.8)
      were placed on the combination therapy. Rate of cognitive decline as measured by
      change in MMSE score per year was significantly slower (p = 0.04, ANOVA) in the
      KUT group (1.4 points) and the combination group (0.4 points) as compared to 4.1
      points in 32 control AD patients (MMSE score: 20.8 +/- 5.6) who received no
      medicines for AD. Any of CSF measures including tau. and A beta 1-42 did not
      differ significantly after KUT therapy. The efficacy of the KUT therapy was most
      obvious at 3 months. Our results suggest that traditional Japanese herbal
      medicine(s) may serve a new interventional strategy for AD.

PMID- 10879070
TI  - [A role of angiotensin II found in knockout mice with angiotensin signal
      breakdown].
AB  - The renin-angiotensin system, composed of enzymatic and signal-transduction
      cascades, plays a key role in the regulation of arterial blood pressure and in
      the development of certain forms of experimental and human hypertension. The
      products of this system, angiotensin peptides, exert a wide range of
      physiologically important effects on many tissues, including those of the
      cardiovascular systems, through their actions on angiotensin receptors. Molecular
      genetic and transgenic studies have begun to implicate some of the genes encoding
      components of the renin-angiotensin system in the development of cardiovascular
      diseases. Here, I review new developments related to the functional role of
      angiotensin II, an important product of the renin-angiotensin system, by focusing
      on knockout approaches including cardiovascular and central nervous systems.

PMID- 10879071
TI  - [Hypertension in the elderly: clinical characteristics].

PMID- 10879072
TI  - [Cognitive function and basic activity of daily living of elderly disabled
      inpatients].
AB  - To elucidate the clinical characteristics of disability due to various basic
      disease groups, by using Japanese Minimum Data Set (MDS), Nishimura's mental
      scale (NM) and activity of daily living scale (N-ADL), cognitive function and
      basic activity of daily living (ADL) together with the grading scale of nursing
      care (freedom-grade of daily living: N1. frequency of bedside visits by a nurse:
      N2) and nutritional function (serum albumin: SA) were assessed in 926 elderly
      disabled inpatients in April 1998 in our long-stay chronic care hospital. Basic
      diseases were divided into five groups: cerebrovascular (C), senile dementia (D),
      bone and joint (B), Parkinson's disease (P) and other diseases (O). (1) In all
      patients, women were 2.9 years significantly older than men. Mean age in disease
      groups was significantly greater in the following decreasing order, B > D > C >
      P. (2) In all patients and patients with C, significant negative correlations
      were found between age and the scores of various scales (NM, N-ADL, N1, SA). In
      patients with D and B, significant negative correlations were found only between
      age and N-ADL and N1, but not NM or SA. In patients with P, no correlations were
      found between age and the various scales. (3) The cognitive function score
      decreased significantly as follows, B > C > P > D and the score of ADL decreased
      significantly as follows, B > D > C > P. (4) In patients with C and P,
      significant positive correlations were found between 3 scores (Cognition, ADL,
      SA). In patients with D, significant positive correlation was found between only
      two scores (ADL, SA) and in patients with B, no correlations were found between
      SA and other scores. (5) Because in all patients and in patients with all disease
      groups, significant positive correlations were found between the scores of
      cognition, ADL by MDS and the scores of NM, N-ADL respectively, the scales of
      cognition and ADL evaluated by MDS were validated for us to assess cognitive
      function and ADL and are probably suitable tools for evaluating elderly disabled
      patients. The other various functional states should also be assessed in elderly
      disabled patients where the quality of life of the patients must take priority
      over other considerations in decision making for medical interventions, including
      care. We should discuss care in detail and continue more medical studies to
      improve the quality of care.

PMID- 10879073
TI  - [Effects of breeding conditions on neurochemical cholinergic and monoaminergic
      markers in aged rat brain].
AB  - We investigated the effects of breeding conditions on neurochemical markers,
      muscarinic receptor (mAChR), beta-adrenoreceptor (beta-AdrR), imipramine binding
      sites (IMBS), choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and
      monoamine oxidase (MAO) activity in aged rat brains. An increase of affinity (Kd)
      and the decrease in the number (Vmax) of mAChR were found in the individual aged
      rats. Concerning IMBS, Kd and Vmax values increased in the individual aged rats.
      However, no significant changes were observed in the beta-AdrR. The increases of
      ChAT and MAO activity were found in the aggregated aged rats to compare with in
      the individual aged rats, while AChE activity decreased in the aggregated aged
      rats. These changes were also particularly seen in the forebrain of aged rats.
      These results indicate that the functions of the central nervous system may be
      reduced in the individual aged rats to compare with in the aggregated aged rats
      under the breeding conditions.

PMID- 10879074
TI  - [Ultrasonographic findings of carotid arteries in female patients with
      arteriosclerosis obliterans and aortic aneurysm].
AB  - To clarify carotid arterial changes in female patients with arteriosclerosis
      obliterans (ASO) and aortic aneurysm (AA), ultrasonographic (US) findings of the
      extra-cranial carotid arteries were studied in 26 patients with ASO (ASO group),
      and 31 patients with AA (AA group), compared to 38 controls (control group) with
      neither ASO nor AA. ASO was diagnosed with an ankle pressure index less than 0.9,
      while AA was done with computed tomography or angiography. Half of the patients
      with ASO were in stage II of the Fontaine clinical staging, and angiography,
      performed in 12, showed femoral arterial obstruction in 10. Most AA patients were
      abdominal aortic aneurysm. Using a high-resolution, real-time, B-mode US
      instrument, the diameter and wall thickness of the common carotids were measured
      bilaterally in the end-diastolic phase, and occlusive changes and plaque were
      estimated. As a risk factor for arteriosclerosis, hypertension, diabetes,
      hyperlipidemia, and cigarette smoking were assessed, in addition to the age, body
      height and weight. Mean ages of each group were 73 to 76.3 year-old. There was no
      significant difference between them in body height and weight. Diabetes,
      cigarette smoking, and cerebrovascular disease were frequent in the ASO group,
      whereas ischemic heart disease was frequent in the AA group. US findings revealed
      that carotid lesions were mostly plaque, and bilateral carotid lesions were
      significantly more frequent in the ASO and AA groups. The mean wall thickness of
      the carotids was greater in the AA and ASO groups, although dilated carotid
      arteries, namely arteriomegaly, was more frequent in the AA group than in the ASO
      and control groups. Stepwise regression analyses demonstrated that strong
      correlations were seen between carotid lesion and two variables [vessel diseases
      (ASO/AA) and cigarette smoking], between carotid diameter and three variables
      (age, AA, and wall thickness), and between the wall thickness and three variables
      (age, vessel diseases and diameter). These findings showed that atherosclerosis
      was not only frequent in female patients with ASO and AA, but arteriomegaly was
      characteristic in female patients with AA. Therefore, it suggested that
      circulatory disturbance in whole organs due to arteriosclerosis should be paid
      attention even in female patients with ASO and AA as well as male patients.
      Furthermore, it is considered that systemic fragility of the arterial media and
      ectasia could be present extensively in patients with AA.

PMID- 10879075
TI  - [Successful total gastrectomy of gastric cancer in a congenital factor V
      deficient patient].
AB  - Congenital factor V deficiency is a very rare hereditary coagulation disorder.
      Total gastrectomy in a patient with factor V deficiency has not been reported in
      Japan. A 71-year-old woman visited our hospital because of gastric cancer and
      gallbladder stone. A preoperative screening examination revealed severe anemia,
      prolonged prothrombin time (35.1 sec.) and activated partial thromboplastin time
      (109.8 sec.) The value of factor V was 8%. Her parents had a consanguineous
      marriage. The level of factor V in her two children and a grandchild were lower
      than the normal limit. We transfused fresh blood and fresh frozen plasma (FFP)
      preoperatively in order to improve anemia and prothrombin time and activated
      thromboplastin time. Operating carefully with transfused FFP and fresh blood, we
      performed total gastrectomy with cholecystectomy successfully. There was no
      serious tendency to hemorrhage during the operation and the postoperative period.
      Enough FFP should be transfused during the pre- and postoperative period, paying
      attention to pulmonary or cardiac failure in elderly patients. Postoperatively,
      during FFP should be used for 3-10 day with under careful observation of wound
      bleeding.

PMID- 10879076
TI  - [A senile case of acute necrotizing myopathy presenting prolonged severe muscle
      paralysis due to high dose glucocorticoid and muscle relaxant].
AB  - An 82-year old man was admitted with dyspnea, productive cough and wheezing. In
      addition to antibiotics (meropenem trihydrate 0.5 g/day), glucocorticoids
      (hydrocortisone 1.250 mg, methylpredonisolone 4.250 mg) were administered for the
      severe bronchospasms. Since his respiratory condition deteriorated, he underwent
      mechanical ventilation using a muscle relaxant (vecuronium bromide, total dose
      776 mg) in combination with high dose glucocorticoid. As his pneumonia improved
      on the 10th hospital day, we started weaning him from the ventilator. However, we
      were unable to complete weaning from the ventilator because of prolonged
      quadriplegia and paralysis of the respiratory muscles. A few days later,
      myoglobinuria appeared. Electrophysiological examinations suggested the
      involvement of both neuromuscular junctions and muscles. Muscle biopsy showed
      rhabdomyolysis. Acute necrotizing myopathy was diagnosed due to high doses of
      glucocorticoid, muscle relaxant, or both. He required about 3 months to be weaned
      from the mechanical ventilation, and another 3 months to leave the hospital.
      Based on our experience, we should consider acute myopathy as an adverse effect
      of glucocorticoids, muscle relaxants or both in elderly patients who require
      mechanical ventilation.

PMID- 10879077
TI  - [Worsened orthostatic hypotension due to levodopa administration in a case of
      Parkinson's disease].
AB  - A 70-year-old woman began to experience gait disturbance in 1995, followed by the
      appearance of action tremor of the left hand in 1996. This tremor was
      subsequently noted in the right hand. Her doctor initially diagnosed Parkinson's
      disease and administered amantadine and levodopa. The gait disturbance and tremor
      improved. However, she stopped taking the medication and her symptoms worsened in
      April, 1998. She was admitted to our hospital, and showed rigidity and action
      tremor predominantly on the left side, frozen gait, postural reflex disturbance
      and orthostatic hypotension. Following levodopa administration, her UPDRS score
      improved from 61.3 +/- 1.2 (mean +/- SD) to 41.7 +/- 5.4. However, she
      experienced a greater decrease in systolic blood pressure following
      administration upon standing, from 12.5 +/- 5.8 mmHg to 17.8 +/- 9.2 mmHg. Thus,
      although levodopa administration led to an improvement in rigidity, tremor and
      akinesia, her orthostatic hypotension worsened. Based on the present results
      clinicians should be aware of the potential of worsened orthostatic hypotension
      when prescribing levodopa to treat Parkinson's disease.

PMID- 10879078
TI  - [Hemodynamics in portal hypertension and treatments for esophagogastric varices].

PMID- 10879079
TI  - [Molecular mechanisms of peritoneal dissemination].

PMID- 10879080
TI  - [IFOBT-positive gastric cancer].
AB  - Among 888 patients who underwent operation or endoscopic resection for gastric
      cancer (1994-1998), 75 patients, who had no colorectal disease or only small
      polyps 5 mm or less in diameter, were positive on the immunologic fecal occult
      blood test (IFOBT) (the positive group). They are compared with the other 813
      patients (the negative group) as to the following 6 points: symptoms, presence of
      anemia, depth of invasion including macroscopic appearance, location, maximum
      diameter of lesions, and microscopic findings. The rate of positive-IFOBT gastric
      cancer was 8.4%. The average blood hemoglobin concentration was significantly
      lower in the positive group than in the negative group. Advanced cancers,
      especially type 2 and 3, were significantly more frequent in the positive group
      than in the negative group. The size of the lesions tended to be larger in the
      positive group than in the negative group. There was no difference between the
      groups as to symptoms, location, depth of invasion and microscopic findings. In
      conclusion, IFOBT-positive patients who have no colorectal disease or only small
      polyps 5 mm or less in diameter should be recommended to undergo upper
      gastrointestinal endoscopy.

PMID- 10879081
TI  - [Treatment of duodenal Crohn's disease with stenosis: case report of 6 cases].
AB  - Treatment for duodenal Crohn's disease with stenosis were analyzed in 6 cases.
      There were 3 men and 3 women, and age at onset of duodenal Crohn's disease ranged
      from 25 to 46 years old. All of them complained of nausea and vomiting, and 4 of
      them complained of upper abdominal pain. Radiographic examination showed stenosis
      of the duodenum in all cases, and endoscopic examination showed cobblestone
      appearance in 3. Endoscopic balloon dilation was attempted in all cases. Two of
      them were successful, but finally the other 4 required gastro-jejunostomy because
      of long, fibrous stenosis. Prognosis was good after the operation in all cases.

PMID- 10879082
TI  - [A case of duodenal adenoma consists of multiple nodular lesions].

PMID- 10879083
TI  - [A case of Crohn's disease associated with neurogenic bladder].

PMID- 10879084
TI  - [A case of iliopsoas hematoma associated with liver cirrhosis, management by
      transcatheter arterial embolization].

PMID- 10879085
TI  - [Interstitial pneumonia observed during acute exacerbation of autoimmune
      hepatitis].

PMID- 10879086
TI  - [Two recovery cases of Wilson's disease initiated with severe hemolysis and acute
      hepatic failure].

PMID- 10879087
TI  - [A resected case of double cancer of hepatocellular carcinoma and
      cholangiocellular carcinoma associated liver cirrhosis C].

PMID- 10879088
TI  - [A case report of a superficial spreading carcinoma of the papilla of Vater].

PMID- 10879089
TI  - [Two cases of pancreatic stones with hyperparathyroidism treated by
      extracorporeal shock wave lithotripsy (ESWL)].

PMID- 10879090
TI  - [A case of primary amyloidosis with marked hepatomegaly and jaundice].

PMID- 10879091
TI  - [Effect of Helicobacter pylori on gastric emptying in non-ulcer dyspepsia--study
      of Helicobacter pylori by employing C13 urea breath test].

PMID- 10879092
TI  - [New strategies of treatment of hemophilia].

PMID- 10879093
TI  - [Treatment of malignant lymphoma: an overview].

PMID- 10879094
TI  - [Detection of potential markers for qualitative abnormalities of hematopoietic
      cells in patients with aplastic anemia].

PMID- 10879095
TI  - [Analysis for hematopoietic disorder using DNA methylation as a molecular
      marker].

PMID- 10879096
TI  - [Morphological subclassification in refractory anemia].

PMID- 10879097
TI  - [Frequent transformation to overt myelodysplastic syndrome in patients with
      aplastic anemia showing hematopoietic monoclonality at onset].

PMID- 10879098
TI  - [Development of myelodysplastic syndrome and leukemia in children with acquired
      anemia].

PMID- 10879099
TI  - [Progression from aplastic anemia to myelodysplastic syndrome/acute leukemia: a
      multi-institutional study group survey by the Ministry of Health and Welfare of
      Japan].

PMID- 10879100
TI  - [Pax-5 genes and CD19 molecules in human myeloma].

PMID- 10879101
TI  - [Identification of gene aberrations involved in the pathogenesis of multiple
      myeloma].

PMID- 10879102
TI  - [Subclassification of multiple myeloma based on the partner genes of
      immunoglobulin heavy chain gene translocations].

PMID- 10879103
TI  - [Relationship between 13q (RB-1 gene) deletion and the prognosis of multiple
      myeloma].

PMID- 10879104
TI  - [The treatment of multiple myeloma: a new molecular target therapy].

PMID- 10879105
TI  - [Bone marrow angiogenesis in multiple myeloma: new insights into the
      pathogenesis, and development of a new therapeutic approach].

PMID- 10879106
TI  - [Prophylaxis with FK-506 for graft-versus-host disease after transplantation of
      bone marrow from unrelated donors].
AB  - Forty-eight patients who underwent bone marrow transplantation (BMT) from
      serologically HLA-matched unrelated donors received tacrolimus (FK506) alone or
      with methotrexate (MTX) and/or methylprednisolone (mPSL) to prevent graft-versus
      host disease (GVHD). We analyzed retrospectively the efficacy of FK506 for GVHD
      prophylaxis, and its toxicity, by comparing three groups of patients: those given
      FK506 alone, those given FK506 + mPSL, and those given FK506 + MTX + mPSL. Grade
      III and IV acute GVHD occurred in five of 10 patients given FK506 alone and in 11
      of 30 patients given FK506 + mPSL. In these groups, severe acute GVHD was
      commonly seen in the patients who discontinued FK506 administration early after
      BMT and in those who received bone marrow from genotypically HLA-mismatched
      donors. Early withdrawal of FK506 was due mainly to severe nephrotoxicity. The
      incidence of nephrotoxicity was very high in patients who received high-dose
      FK506 as well as melphalan-containing preconditioning (80% and 50%). None of
      eight patients who received FK506 + mPSL + MTX developed grade III-IV acute GVHD
      even though five of them received bone marrow from genotypically HLA-mismatched
      donors. In patients receiving bone marrow from unrelated donors, adjustment of
      the initial dose of FK506 seems essential in order to avoid severe
      nephrotoxicity, and combination of MTX and FK506 is useful for preventing severe
      acute GVHD.

PMID- 10879107
TI  - [Hypokalemic periodic paralysis during treatment of acute promyelocytic
      leukemia].
AB  - A 40-year-old man was admitted with fever and purpura. He was diagnosed as having
      acute promyelocytic leukemia, and treated with all-trans retinoic acid. After
      achieving complete remission, he received consolidation therapy. During the
      chemotherapy, quadriplegia occurred three times. This was diagnosed as
      hypokalemic periodic paralysis because of the patient's low serum potassium
      level. Results of hormone and urine examinations showed no indication of
      secondary hypokalemia. However, the patient had a history of quadriplegia of
      unknown etiology at the age of 36. We speculated that in addition to the
      patient's predisposition to hypokalemic periodic paralysis, chemotherapy
      including prednisolone, and excessive ingestion of carbohydrate had induced his
      quadriplegia.

PMID- 10879108
TI  - [Copper deficiency anemia and neutropenia secondary to total gastrectomy].
AB  - We report a case of copper deficiency with anemia and neutropenia due to dumping
      syndrome after total gastrectomy. Parenteral nutrition containing cupric sulfate
      promptly improved the dumping syndrome, anemia and neutropenia. This case
      suggests that total gastrectomy with dumping syndrome can cause copper
      deficiency, and that copper deficiency should be considered when encountering
      similar patients with severe anemia and neutropenia.

PMID- 10879109
TI  - [Body plan of ancestral type animals and the evolution].

PMID- 10879110
TI  - [Anti-adhesion molecule tenascin of the cell].

PMID- 10879111
TI  - [Glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan
      protein linkage region of proteoglycans].

PMID- 10879112
TI  - [Evolutionary molecular engineering for enzymes].

PMID- 10879113
TI  - [Functional analysis of angiotensin II receptor subtypes by gene targeting].

PMID- 10879114
TI  - [Structure and functional diversity of membrane-type phosphatidylinositol
      transfer protein/Drosophila rdgB homologue].

PMID- 10879115
TI  - [Dynamic structure of muscle motor protein actin-myosin complex].

PMID- 10879116
TI  - ["Structural biology of proteins and nucleic acids: molecular basis of
      noncanonical structures"].

PMID- 10879117
TI  - [Histone modification enzymes and chromatin structure].

PMID- 10879118
TI  - [Transcriptional co-activator CBP and co-repressor Ski/Sno].

PMID- 10879119
TI  - [Transcriptional regulation of chromatin by SWI/SNF protein complex].

PMID- 10879120
TI  - [Regulation of transcription by locus control regions].

PMID- 10879121
TI  - [Structure and function of chromatin centered on histone acetyltransferase and
      histone deacetylase].

PMID- 10879122
TI  - [DNA methylation and chromatin modification on transcription].

PMID- 10879123
TI  - [Mechanism of basal transcription].

PMID- 10879124
TI  - [Regulatory mechanism of transcription elongation: DRB-sensitive elongation
      control machinery].

PMID- 10879125
TI  - [Functional roles of TFIID subunits (TAFs) in eukaryotic transcription].

PMID- 10879126
TI  - [Regulation mechanisms of two sequential reactions, transcription initiation and
      the transition from initiation to elongation, by general transcription factors].

PMID- 10879127
TI  - [Role of TFIIH in transcriptional regulation].

PMID- 10879128
TI  - [Function of transcriptional elongation factors, TFIIF and elongin in gene
      regulation].

PMID- 10879129
TI  - [Activation of transcriptional factor by signal transduction: overview].

PMID- 10879130
TI  - [Transcriptional regulation by Ah (dioxin) receptor].

PMID- 10879131
TI  - [Transcriptional control by nuclear vitamin A/D receptors].

PMID- 10879132
TI  - [I kappa B kinase (IKK) complex].

PMID- 10879133
TI  - [Functional role of IRF--family transcription factors].

PMID- 10879134
TI  - [Phosphorylation-dependent regulation of transcription factors].

PMID- 10879135
TI  - [Regulation of hematopoiesis by transcription factors].

PMID- 10879136
TI  - [Study of the transcription factor function in vivo: an overview].

PMID- 10879137
TI  - [Critical roles of the CCAAT/enhancer-binding protein family].

PMID- 10879138
TI  - [Molecular bases of neuronal diversity in the vertebrate CNS].

PMID- 10879139
TI  - [An approach to analyze transcription factor function in vivo utilizing specific
      gene regulatory regions].

PMID- 10879140
TI  - [Regulatory mechanisms and transcription factors for cell differentiation and
      body morphogenesis].

PMID- 10879141
TI  - [Regulation of neuronal differentiation by bHLH factors].

PMID- 10879142
TI  - [Mechanisms that regulate morphogen activity in pattern formation].

PMID- 10879143
TI  - [L-Maf and N-cadherin during lens development].

PMID- 10879144
TI  - [Transcription factors and growth factors implicated in gonad differentiation].

PMID- 10879145
TI  - [Regulation of immune system by polycomb group genes].

PMID- 10879146
TI  - [Studies of regulation of gene expression developed from genomic science].

PMID- 10879147
TI  - [Structure-function relation of transcriptional factors: an out line].

PMID- 10879148
TI  - [Structures of proteins that regulate chromatin structures].

PMID- 10879149
TI  - [DNA recognition by DNA-binding proteins].

PMID- 10879150
TI  - [DNA-recognition by helix-turn-helix variants in DNA-binding domains].

PMID- 10879151
TI  - Estrogen: a heart-healthy hormone?

PMID- 10879152
TI  - Helping the patient by helping the caregiver.

PMID- 10879153
TI  - The facts about drinking to your health.

PMID- 10879154
TI  - Leading an active life with atrial fibrillation.

PMID- 10879155
TI  - Does age-related macular degeneration (AMD) cause blindness?

PMID- 10879156
TI  - How do the new injections for arthritis of the knee work, and who is a good
      candidate for this treatment?

PMID- 10879157
TI  - [An adventure of the human intellect. Max Planck and the centenary of quantum
      theory].

PMID- 10879158
TI  - [Considerations on the health technician's code of conduct in medical radiology].

PMID- 10879159
TI  - [The larynx: an anatomical and functional echographic study].
AB  - PURPOSE: To investigate the capabilities of US in morphological and functional
      studies of laryngeal structures. MATERIALS AND METHODS: We examined 50 healthy
      subjects (30 women and 20 men) ranging in age 23 to 74 years; 17 of them were
      professional opera singers. The patient was laid supine, with his/her neck in
      marked hypertension, and images were acquired with the vocal cords at rest, and
      during quiet breathing inspiratory and expiratory standstill, Valsalva, and
      wording of "e" and "o". We used 7.5-12.0 MHz probes to perform (para)median axial
      scans with anteroposterior and caudocranial US beam incidence. RESULTS: All the
      anatomical structures that could be measured were clearly demonstrated. The
      length of the true vocal cords was 16-28 mm in women and 20-23 mm in men and
      their wideness 7-15 mm to the dorsal end 2-4 mm to the ventral and; maximum
      thickness ranged 2-10 mm. The respiratory space varies 2-8 mm in the different
      phases of respiration and speech. In the 17 opera singers we found agreement
      between length of the vocal cord compass: basses had 30-33 mm and tenors 21-25
      mm. DISCUSSION AND CONCLUSIONS: In addition to the advantages US is known to
      provide, it can also permit accurate measurements of the anatomical structures of
      the larynx and respiratory space at rest and in the dynamic phase, which are
      important data in some conditions (e.g., cord paralysis) or follow-up of drug or
      rehabilitation treatment. Finally US can permit to detect atypical situations
      such as those in false/true vocal cords hypertrophy and abnormal cord growth.

PMID- 10879160
TI  - [Transbronchial needle aspiration: a well-known technic but still not
      sufficiently applied].

PMID- 10879161
TI  - [Density-mask spiral computed tomography in patients who are candidates for a
      lung-volume-reduction intervention: a preliminary study].
AB  - PURPOSE: To investigate the usefulness of helical CT with multiplanar
      reconstructions and density mask in emphysematous patients candidate for lung
      volume reduction surgery (LVRS), in order to assess the feasibility of surgery
      and for surgical planning. MATERIAL AND METHODS: Twenty emphysematous patients (5
      women and 15 men; age range: 55-67 years, mean: 61) candidate for LVRS were
      submitted to isotope perfusion scanning, chest radiography during maximal
      inspiration and expiration and Helical CT with the low volume contrast technique,
      multiplanar reconstructions and density mask. RESULTS: Only 8 of the 20 patients
      examined were submitted to LVRS. They had irregular distribution of emphysema at
      isotope perfusion scanning and density mask CT. Surgery consisted in an atypical
      resection of the upper lobe portions which appeared most damage with both
      techniques. Six of the remaining 12 nonsurgical patients were excluded because of
      homogeneous distribution of emphysema at both CT and perfusion scanning, which
      was incompatible with surgery. Lung transplant was considered for 4 of these
      patients, but only 2 of them actually received it. Three patients were excluded
      from LVRS because of excessive diaphragm excursion during expiration at chest
      radiography and of multiple confluent areas of emphysema in both lung at CT and
      perfusion scanning. One patient with a large area of emphysema in the right upper
      lobe at CT and perfusion scanning was excluded due to associated severe
      interstitial disease. Another patient with emphysema mainly involving the lower
      lobes, as clearly depicted with both techniques, was excluded because the
      emphysema was secondary to alpha 1-antitrypsin deficiency, a condition known to
      have a less favorable surgical outcome. Finally, one patient was excluded due to
      a previous upper transverse laryngectomy, although CT and perfusion scanning
      patterns were compatible with surgery. CONCLUSIONS: In our opinion, density mask
      helical CT yields more accurate and clearer images than perfusion scanning, and
      allows the patients candidate for surgery to undergo a single examination to
      evaluate the extent and distribution of emphysema and to detect other possible
      pathological conditions. Though ours was a small series, the results suggest that
      perfusion scanning be integrated with density mask helical CT, the latter a very
      important technique for surgical planning.

PMID- 10879162
TI  - [Craniocerebral trauma from bullets: the correlation between computed tomography,
      the clinical picture, neurosurgical treatment and the long-term sequelae].
AB  - PURPOSE: To demonstrate the usefulness of CT findings in the planning of brain
      neurosurgery in gunshot victims, for prompt and successful treatment. MATERIAL
      AND METHODS: Thirty patients with brain gunshot wounds were examined with CT over
      5 years. The patients were 27 men and 3 women whose mean age was 33 years (range:
      17-56). Brain CT was carried out with thin (5-mm) slices and 10-mm gap; dynamic
      scanning (3-mm interscan time) was used especially in case of posterior fossa
      involvement and diffuse brain damage. The examination was integrated with
      cervical scout views to detect bullets in the neck and cervical dislocation. CT
      follow-up was carried out in 20 patients 24 hours postoperatively and every 6
      hours in 9 patients in a severe postoperative coma. RESULTS: Twelve intracranial
      hematomas and 9 subdural hematomas, 3 of them bilateral, were treated and
      hemorrhage was resolved in 8 lacerocontusive foci. Skull plastic surgery was
      carried out in 5 cases. Surgical maneuvers were most difficult in the 5 crash
      bone injuries with wedged splinters; postoperative subarachnoid hemorrhage
      followed in 3 cases. Blood effusion in ventricles was drained in 6 cases; in 2 of
      them with permanent catheters. Eleven patients died: 4 right after surgery and 7
      an average 15 days postoperatively. DISCUSSION AND CONCLUSIONS: In our series the
      mortality rate of firearm wounds of the skull base was 34% higher than that of
      the hemisphere; this is due to carotid hemorrhage and midbrain damage. Such
      traumas require emergency radiological diagnosis and neurosurgical treatment
      because of their severity and early irreversible complications. Complex
      operations and skilled surgeons may prevent disabling postoperative sequels. CT
      findings are indispensable and must be correctly interpreted. The radiologist and
      the neurosurgeon must collaborate closely and both must consider several
      diagnostic and prognostic factors affecting surgical planning.

PMID- 10879163
TI  - [Power Doppler signals produced by static structures: a frequent cause of
      interpretation errors in the study of slow flows].
AB  - INTRODUCTION: The main characteristic of power Doppler US is its high sensitivity
      in showing blood vessels with small caliber and slow flow. However, artifacts are
      a common problem with this technique and they lead to impaired and subjective
      image reading. We analyzed the artifacts from Power Doppler signals from static
      structures both in vitro and in vivo. MATERIAL AND METHODS: Some samples of
      different tissues (liver, muscle, fat) positioned into a water bath were studied
      with Power Doppler in vitro. The static structures were imaged with a 10 MHz
      transducer (Esaote AU4, Genoa, Italy) both through water and with the transducer
      resting directly on the tissue. PRF and WF were set differently every time and
      their individual/combined role in causing artifacts was assessed. Then we
      examined different organs in vivo to investigate if the same setting as in vitro
      would cause the same artifacts. RESULTS: All our tissue samples exhibited strong
      and persistent color signals at low PRF and WF settings, with stronger signals at
      the solid/liquid interface and no signals from the liquid color box. Comparison
      of images acquired with same setting, particularly color gain, but different PRF
      (750 Hz to 3 KHz) or WF (50 to 600 Hz) showed that artifacts are mainly related
      to the latter. In vivo examinations showed similar findings, especially relative
      to the liquid/solid and solid hypoechoic/solid hyperechoic interfaces.
      CONCLUSIONS: Persistent and fairly strong Power Doppler signals can be produced
      by echogenic structures with no flow; these artifacts are frequent at low PRF,
      but are mainly caused by incorrect WF setting. They are most frequent along
      interfaces with specular reflection. To conclude, we would like to stress that,
      in addition to motion artifacts, which are easier to recognize, other potentially
      misleading signals may come from static structures.

PMID- 10879164
TI  - [The role of spiral computed tomography in sigmoid diverticulitis and the
      diagnostic-therapeutic implications].
AB  - PURPOSE: Colonic diverticula are saccules made of colonic mucosa and submucosa
      that herniate from the colonic lumen through the muscular layer of the wall where
      straight vessels penetrate. Diverticula are localized in the sigmoid colon in 95%
      of cases. Bacteria pooling in the lumen may cause lumen erosion and eventually
      perforation. CT is a useful technique in this condition because it can
      demonstrate intra- and/or extramural inflammation. Aim of this retrospective
      study was to assess the capabilities of contrast-enhanced helical Computed
      Tomography (CT) in sigmoid diverticulitis, especially relative to selection of
      the appropriate treatment. MATERIAL AND METHODS: We retrospectively reviewed the
      findings of 41 patients referred to our emergency department for diverticulitis.
      CT scans were performed 65 seconds after i.v. injection of nonionic contrast
      material (3 mL/s, 120 mL in all) administered by a CT-power injector. The
      following 7 CT findings were considered at least suggestive of acute
      diverticulitis: focal wall thickening, intramural abscess, inflammatory changes
      in the sigmoid mesentery root, pericolic fat inflammation or pericolic abscess
      formation, fistula, peritonitis. CT results were compared with surgical and
      physical findings. RESULTS: Based on CT findings, diverticulitis was classified
      as mild (25 patients) or severe (15 patients). In mild diverticulitis we found:
      focal sigmoid wall thickening (6 patients), intramural abscess (3 patients),
      sigmoid mesentery root thickening (5 patients), edema fluid (8 patients) and
      phlegmon (3 patients). In severe diverticulitis we found: sigmoid mesentery
      abscess (6 patients), fistula (5 patients) and peritonitis (4 patients). CT
      findings were questionable in 1 case and thus we could not exclude a perforated
      carcinoma. CONCLUSION: Contrast-enhanced helical CT is the imaging modality of
      choice in assessing mild or severe acute diverticulitis because it provides
      useful information for appropriate treatment planning in the emergency setting.
      This technique is most useful in questionable cases and in patients with
      suspected severe diverticulitis where a choice must be made between different
      treatment options.

PMID- 10879165
TI  - [Suburban amebiasis: the diagnostic aspects via computed tomography and
      echography and the percutaneous treatment of amebic liver abscesses].
AB  - INTRODUCTION: Liver is the most common site of extraintestinal amebiasis and
      hepatic abscesses are the most frequent symptom, occurring in 3-9% of patients
      with amebic infection. Several studies have shown that drug treatment is more
      efficacious when combined with percutaneous drainage of the abscess, yielding
      quicker recovery and a positive body response. We report our US and CT findings
      in 16 patients with amebic abscesses, 12 of whom lived in a temperate peripheral
      area north-east of Naples. All patients had a clinical-diagnostic condition that
      we called "suburban amebiasis". Finally we report our personal experience with
      the US-guided therapeutic drainage of amebic abscesses with repeated cavity
      washings, which is important for positive parasitology. MATERIAL AND METHODS: We
      retrospectively reviewed the findings of 16 patients (11 men and 5 women; age
      range 36-78 years; mean 52) with amebic abscesses of liver examined with US and
      CT. US with a 3.5 MHz transducer was the technique of choice in all patients. 94%
      of liver abscesses and some extraintestinal complications were easily shown with
      this technique. CT angiography was then performed to detail and clarify US
      findings. Abscesses over 4 cm in diameter were submitted to US-guided
      percutaneous treatment which permitted abscess drainage, the collection of
      material for parasitology and repeated cavity washings. RESULTS: US showed
      multiple liver abscesses in 12 patients, which were multiseptate and formed by
      multiple hypo-/hyperechoic microabscesses in 4 of them. Four non-European
      patients had a single abscess, which is typical of tropical endemic forms. CT
      showed the amebic abscesses as hypodense roundish masses with clear-cut outline
      most often localized in the right lobe in the 12 multiple cases. After
      percutaneous drainage 13/16 patients (81%) reported less pain in the right
      hypochondrium and had a lower temperature; their hospitalization was also
      shorter. DISCUSSION AND CONCLUSIONS: Combined US and CT assessment facilitated
      the diagnosis of amebiasis and its differentiation from pyogenic abscess and
      hepatoma. The combination of US-guided drainage and drug treatment provides
      better results than either treatment alone and quicker improvement of patient
      conditions, with fewer extraintestinal complications. Percutaneous drainage
      should be used in abscesses bigger than 4-5 cm, those with questionable clinical
      laboratory findings and finally those failing to respond to drug treatment alone.
      Positive parasitology of abscess content is related to repeated cavity washings
      after percutaneous drainage, likely because peripheral layers are much richer in
      amebae.

PMID- 10879166
TI  - [A statistical evaluation of the variability in the measurements of the resistive
      index in kidney transplantation].
AB  - INTRODUCTION: Doppler ultrasound (US) is a valuable tool to measure blood flow in
      the transplanted kidney, but its operator-dependence can greatly affect
      repeatability and reproducibility of measurements. Aim of this work was to
      evaluate intraobserver and interobserver variability in measuring the resistive
      index (RI) in renal transplants. PATIENTS AND METHODS: Ten renal transplant
      recipients were randomly selected among those undergoing follow-up and examined
      by two operators (FG and LB) with 3.5 MHz and 10 MHz scanheads to assess the
      variability of RI measurements. Each observer obtained two measurements of the RI
      with each scanhead within a 10-15 minutes' period. In all, 80 measurements were
      made, 4 per patient per observer. The statistical analysis included two-tailed
      Student's t-test for paired data and calculation of repeatability/reproducibility
      coefficients. RESULTS: Student's t-test analysis demonstrated a statistically
      significant difference (p = 0.037) between the means of the first and second
      measurements by FG with the 3.5 MHz scanhead and the first and the second
      measurements by LB with the same scanhead. Differences between the other means
      were not statistically significant. Intraobserver variability ranged 0.03 units
      (or 2.07%) and 0.07 units (or 4.24%), while interobserver variability was 0.04
      units with both 3.5 and 10 MHz scanheads, or 3.61 and 3.73%, respectively.
      CONCLUSIONS: Doppler US of renal transplants has statistically quantifiable
      operator-dependent variability: the possible evidence of statistically
      significant differences can be minimized by having the same operator make the
      measurements. However, RI variations ranging 0.02 to 0.04 units should not be
      considered significant.

PMID- 10879167
TI  - [Calcified renal metastases: their etiology, pathogenesis, computed tomographic
      aspects and differential diagnosis].
AB  - PURPOSE: To describe CT findings of calcified renal metastases focusing on
      differential diagnosis problems. MATERIAL AND METHODS: We retrospectively
      reviewed abdominal CT scans of 8000 patients with tumor, performed from 1984 to
      1998. Among the 58 renal metastases, 9 showed a calcific component. We evaluated
      the location, morphostructural pattern, histology of the primary lesion, the
      synchronous or metachronous character and the type of treatment. All the lesions
      were pathologically proved. RESULTS: The primary histotype of the 9 metastases
      was as follows: 4 mucin-producing adenocarcinomas of the large bowel, 1 gastric
      mucinous adenocarcinoma, 1 chondrosarcoma, 1 osteosarcoma, 1 melanoma, 1
      papillary thyroid carcinoma. In all the cases the renal metastasis was unilateral
      and unifocal. Granular multiple calcifications were demonstrated within the
      metastases of mucin-producing adenocarcinoma of the large bowel (3), within the
      metastasis of chondrosarcoma (1) and of melanoma (1). Diffuse "star-like"
      calcifications were demonstrated in renal metastases of mucin-producing
      adenocarcinoma of the large bowel and of gastric mucinous adenocarcinoma (1).
      Peripheral "egg-shell" calcifications were demonstrated in renal metastasis from
      papillary thyroid carcinoma (1). Completely calcified monofocal calcification was
      demonstrated in renal metastasis from osteosarcoma (1). DISCUSSION AND
      CONCLUSIONS: Calcified renal metastases are rare lesions related to specific
      oncotypes. The differential diagnosis (carcinoma with calcifications,
      osteosarcoma, chondrosarcoma, nephrocalcinosis, granulomatosis, hydatidosis etc.)
      is particularly difficult because of the aspecificity of the morphostructural
      pattern. Diagnosis is based on a history of specific oncotypes (papillary and
      mucin-secreting carcinomas, osteosarcoma and chondrosarcoma), but in most cases
      it requires pathologic confirmation.

PMID- 10879168
TI  - [Complaints against radiologists in Italy].
AB  - INTRODUCTION: Legal claims against radiologists are a relevant phenomenon also in
      our country and represent an increasing risk for a radiologist's professional
      activity. MATERIAL AND METHODS: We reviewed the 1993-1998 insurance claims
      against Italian radiologists. We found 259 claims subdivided by type into: 1)
      misdiagnosis; 2) complications of the examination; 3) missed referral for further
      examinations/treatment; 4) (non)ionizing radiation treatment; 5) slip-and-fall
      injuries; 6) miscellaneous cases. All claims were reviewed anonymously. RESULTS
      AND DISCUSSION: Most of the 259 malpractice claims were filed late after the
      event, which makes the actual incidence of the phenomenon difficult to evaluate.
      Nevertheless the incidence of malpractice claims can be estimated at 32 per
      thousand people a year, meaning that an Italian radiologist's risk of being sued
      by a patient at least once in his/her professional life exceeds 1. Alleged
      misdiagnosis was the most frequent claim category. Missed bone abnormalities of
      any type, including fractures, dislocations, malignant lesions and other
      nonspecific conditions accounted for 52.9% of cases. Missed abnormalities on
      breast and chest examinations accounted for 17.5% and 15.3%, respectively. Within
      this claim category, missed breast lesions exhibited the most increasing trend.
      Alleged complications from radiological examinations accounted for 20% of cases
      and mostly involved i.v. contrast agent administration, interventional procedures
      and barium enema. Slip-and-fall injuries, where the patients falls off the
      examination table, slips on the floor, bumps into a piece of equipment and so on,
      accounted for 7% of cases. Missed referral to further examinations accounted for
      1.5% only. Finally, radiologists were frequently sued as one of many defendants,
      together with medical/surgical doctors, in case of patient's death, in 20% of all
      cases. CONCLUSIONS: Italian radiologists currently run the same risk of being
      sued for malpractice as their American colleagues. Strict compliance with
      radiological standards is recommended to try to decrease the risk and to obviate
      litigation.

PMID- 10879169
TI  - [A case of gossypiboma of the knee. Its computed tomographic diagnosis].

PMID- 10879170
TI  - [An atypical form of osteochondroma. A case report].

PMID- 10879171
TI  - [A case of nodular fasciitis of the tensor muscle of the fascia lata].

PMID- 10879172
TI  - [Panniculitis of the neck. A case report].

PMID- 10879173
TI  - [Inflammatory pseudotumor of the breast. A case report].

PMID- 10879174
TI  - [Atypical presentations of pulmonary sequestrations (2 cases)].

PMID- 10879175
TI  - [A case of metastasis to the corpora cavernosa from a bladder carcinoma].

PMID- 10879176
TI  - [Bladder leiomyosarcoma: the computed tomographic aspects in 2 cases].

PMID- 10879177
TI  - [A report of a family affected by a Li-Fraumeni type of syndrome with adrenal
      cortical carcinoma in an adult. A case].

PMID- 10879178
TI  - [E pluribus unum].

PMID- 10879179
TI  - [Studies on properties of biofriction and wear for friction pairs of UHMWPE and
      Ti matrix-TiN-TiC gradient film materials].
AB  - In order to search the possible application of friction pairs of UHMWPE and
      Ti6Al4V-TiN-TiC etc. gradient materials to total hip joint replacements, we have
      prepared Ti6Al4V-TiN-TiC etc. gradient film materials by using N ion implant, d.
      c plasma CVD(PCVD). The properties of biological friction and wear for friction
      pairs of HUMWPE and Ti6Al4V-TiN-TiC etc. gradient film materials were
      investigated. The friction coefficient of friction paris and the wear loss of
      worn UHMWPE were measured; the surface morphology was observed by SEM. It has
      been shown that in human serum lubrication the wear loss of HUMWPE decreases with
      the increase in the surface hardness of its pairing ceramic film material. The
      pairing Ti6Al4V-TiN-TiC gradient film material possesses highest surface
      hardness, compared with other materials studied; UHMWPE wear loss in lowest. The
      wear mechanism of studied pairs has been analysed as well in the present paper.

PMID- 10879180
TI  - [Preparation, characterization and drug release characteristics of
      poly(lactide)(PL)/poly(lactide-co-polyethylene glycol)(PLEG) blend microspheres].
AB  - PL and PLEG are biodegradable, biocompatible polymers. They have been widely used
      for controlled release of drugs. We synthesized PLEG copolymers containing PEG
      segments with various molecular weight and prepared hCG-loaded PL/PLEG blend
      microspheres to improve hCG entrapment efficiency. It was shown that the hCG
      entrapment effciency of PL/PLEG microspheres was higher than that of PL or PLEG
      microspheres when P(L-co-PEG6000)(90:10) was used. In vitro release test showed
      that the release of hCG was a burst-slow process, which was thought to be good
      for antigens to produce antibodies.

PMID- 10879181
TI  - [Modification of surface of Dacron materials by UV irradiation for prevention of
      microbial adhesion].
AB  - UV irradiation grafting method was used to modify the surface of Prosthetic Valve
      materials (Dacron) for prevention of bacteria-adhesion, and PEG was introduced to
      the surface of Dacron by this method. The result showed that the chemical
      magnifying effect of PEG improved the grafting of heparin on the material
      surface. This method can obviously reduce the number of adherent bacteria.

PMID- 10879182
TI  - [Physical properties of apatite bone cement].
AB  - Some properties of the apatite bone cement which is composed of alpha-tricalcium
      phosphate and hydroxyapatite for use as a biomaterial were investigated. The
      powder of cement was synthesized from calcium phosphate, calcium carbonate and
      dicalcium phosphate by solid reaction. Several kinds of citric acid solutions
      were used for hardening. When the liquid for hardening was 30% (w/w) citric acid
      solution, the setting time was about six minutes, the compressive strength of
      hardened bodies was 24.96 MPa, and the solubility was about 1.4 wt%. The
      compressive strength was increased by the addition of Na or K salt. Especially,
      when copolymer of acrylic acid/itaconic acid was added to the liquied, the
      strength was increased about three times, but the setting time was significantly
      shortened. The results of this study indicate that the apatite bone cement is a
      potentially highly useful biomaterial for dental and medical applications.

PMID- 10879183
TI  - [Study of covalently immobilizing heparin to polyetherurethane surface].
AB  - In this paper an approach of covalently immobilizing heparin to the surface of
      polyetherurethane without functional groups was studied. By quantitation of amino
      groups on PEU surface, the appropriate hydrolysis condition to PEU was
      determined. The assays of the heparin content heparinized PEU and the time of
      recalcification proved the above approach comparatively ideal.

PMID- 10879184
TI  - [Evaluation for biocompatibility of poly-(3-hydroxypropyl)-DL-aspartamide].
AB  - To evaluate the biocompatibility of poly-(3-hydroxypropyl)-DL-aspartamide(PHPA),
      we utilized the laboratory methods, including subcutaneous implantation,
      histological examination, blood biochemical and micronucleus test. Histological
      examination revealed a nonspecific foreign body reaction around the PHPA and a
      slight inflammation around the small blood vessels of the liver on the 13th day,
      but all these reactions diminished or disappeared gradually after 34 days of
      implantation. The structures and functions of liver and kidney were normal. The
      results indicate that PHPA possesses a good nature in biocompatibility.

PMID- 10879185
TI  - [Magnetic drug delivery system--adriamycin-carboxymethyl dextran magnetic
      nanoparticles].
AB  - A novel magnetic drug carrier-carboxymethyl dextran magnetic nanoparticles(CMD
      MNPs) was prepared. Adriamycin (ADR) was coupled with two types of carrier
      neutral dextran MNPs and anionic CMD MNPs, by periodate oxidation. The physico
      chemical characteristics and the magnetic guidance effects in vitro and in vivo
      of ADR-CMD MNPs were studied. The distribution profiles of liver and spleen in
      mice were studied for both ADR-dextran conjugate MNPs and ADR-CMD conjugate MNPs.
      The results showed ADR-CMD conjugate MNPs possessed superparamagnetism, the mean
      diameter was 56 nm, the mass magnetic susceptibility was 1.06 x 10(-4) emu.g-1,
      and the drug loading was 12.4%. The distribution profiles in liver and spleen
      revealed that conjugation with neutral dextran MNPs, excessive accumulation of
      loaded ADR was found in liver and spleen after intravenous administration, while
      conjugation with CMD MNPs gave a markedly lower concentration in these organs,
      which indicated less uptake of ADR-CMD conjugate MNPs by reticuloendothelial
      system(RES) and the advantage of delivering loaded drug to sites other than the
      RES; thus it opens a new perspective for the active delivery of drug.

PMID- 10879186
TI  - [The in vivo degradation, adsorption and excretion of poly(epsilon
      caprolactone)].
AB  - The in vivo degradation of poly(epsilon-caprolactone(PCL) was studied in rats.
      The results showed that the PCL capsules with an initial molecualr weight of
      66,000 stayed intact in vivo for 2 years, although the molecular weight of the
      capsules gradually declined during the two-year implantation. It then degraded
      into low molecular wight pieces with the extension of the implantation. Tritium
      labeled low molecular weight PCL was subcutaneously implanted in rats to further
      investigate the absorption and excretion of the material. The radioactivity was
      first detected in blood 15 days post the implantation. At the same time
      radioactive excreta were recovered from feces and urine. An accumulative 92% of
      the implanted radioactive dosage was excreted from feces and urine 135 days post
      the implantation. In the meanwhile, the blood radioactivity dropped to the
      background level. Radioactivity in the organs was all close to the background
      level indicating that the material did not cumulate in body tissue and could be
      completely excreted.

PMID- 10879187
TI  - [Improved liposome encapsulated hemoglobin by electret technology and its
      influence on the blood rheologic behavior in vitro].
AB  - To study the influence of different electret properties of Liposome Encapsulated
      Hemoglobin(LEH) on the blood rheologic behavior in vitro, four kinds of LEH have
      been prepared. Their electret properties have been determined by using Thermally
      Stimulated Depolarization Current(TSDC). The results show that 4# LEH, whose Ta
      is 12 degrees C and Ia is -5.6 x 10(-9) A, has the best electret property,
      furthermore, the results of the thrombus formation in vitro also show that the
      addition of 4# LEH induces the lightest thrombus figuration in vitro. It is
      obvious that the rational improvement of the electret property of LEH can
      meliorate the surface charge of blood and effectively inhibit the formation of
      thrombus.

PMID- 10879188
TI  - [Investigation of infiltration glass of the machinable infiltrated ceramic(MIC)].
AB  - To explore the manufacture arts and determine the properties of the infiltration
      glass of the MIC. In order to determine the glass forming range of the MIC
      infiltration glass, molten glass was prepared in Al2O3 crucibles by heating the
      components to 1450 degrees C. Thermal analytic device was employed to study the
      thermal properties of the glass. Its crystal phases after micro-crystallization
      were analyzed with XRD. Flexural strength was measured by means of 3-point
      bending test. The chemical components of MIC glass were determined. Conventional
      fluorophlogopite glass was converted into an infiltration glass with low
      viscosity, good infiltration capability and low fusing temperature by introducing
      B2O3, La2O3 and Li2O into the glass. Fluorophlogopite crystals formed after
      crystallization. Conventional mica glass can be changed according to the
      requirements of properties. Modified mica MIC glass in this study has good
      infiltration ability in Al2O3 matrix while remains machinability.

PMID- 10879189
TI  - [3-D direct matching interpolation for rotary scanning echo-cardial images].
AB  - In the present paper, a method of three dimension direct matching interpolation
      for a series of 2-D echo-cardial images with intersecting each other and
      arranging at an angle in space has been developed. It is different from the
      conventional interpolation. During the interpolation, sectional images are
      acquired and the 3-D spatial position of "empty voxel" in sectional images is
      located; secondly, the cubic volume is constructed, and the motion orbit of
      images between two windows where the nearest original image intersects to the
      volume is found up, passing through the "empty voxel"; In the end, based on the
      matching pixels, the "empty voxel" is interpolated. This method simplifies the
      two interopolating procedures of the conventional methods into one procedure, and
      overcomes the shortcoming of the overlap of image data. Experiments show that the
      accuracy and reasonability of interpolation can be improved by the proposed
      method.

PMID- 10879190
TI  - [The alpha-dissipation characteristic of human auricular points].
AB  - We researched into the dissipative characteristic of human auricular points in 40
      cases of myopia. The logZ-logf curve of the dissipative characteristic of the
      otopoint is similiar to the dermal alpha-Dispersion in 1-100 kHz of the
      alternating electric field. The dissipative effect of the otopoint is generated
      mainly by the skin of the body surface. The characteristic frequency f0 has
      intimate relation to patholgic change, correlation coefficent r approximately
      0.8. The f0 has characteristic reflecting pathologic change, P < 0.01. The
      relexation time tau signifies the space constructive characteristic of the
      tissue. So we suppose that the otopoint and its characteristic reflecting
      pathologic change essentially relate to the change of biological macromolecule
      conformation of the dermatic tissue under acupoint.

PMID- 10879191
TI  - [Experiments on elimination of the noise in NEMG by adopting wavelet transform].
AB  - Wavelet transform (WT) is a promising technique for time-frequency analysis. By
      decomposing signals into elementary building blocks that are well localized both
      in time and frequency, the WT can characterize the local regularity of signal. In
      this paper, we process the needle electrode electromyography (NEMG) signal with
      noise by adopting WT and have completed the contrast experiments. The results
      show that WT is an effective method by which high frequency noise and baseline
      drift in NEMG can successfully be eliminated by selecting proper transform scales
      of WT.

PMID- 10879192
TI  - [Application of bio-electrical impedance analysis in the compensation period of
      intracranial pressure increasing].
AB  - In the compensation period of intracranial pressure increasing, brain impedance
      rises continuously while cerebrospinal fluid volume changes. Along with the
      illness progressing, intracranial pressure would rise obviously, but the
      intracranial component relative volume would go near to constant; at the same
      time, brain impedance fluctuates around a baseline and there appears an
      inflection point on the impedance track record curve after the compensation
      period.

PMID- 10879193
TI  - [High resolution time-frequency analysis method for extracting the sleep
      spindles].
AB  - In this paper, a new method for the auto-detection sleep spindle is presented.
      The method is based on the Discrete Gabor Spectrogram (DGS), a high resolution
      time-frequency analysis. Sleep EEG5 were processed and the spindles were
      accurately detected. By, this method the accuracy of auto-detection almost
      approched the level of visulal detection. Auto-detection of sleep spindles could
      release the expert from reading long term sleep EEG and provide useful
      information for sleep studies.

PMID- 10879194
TI  - [The development of an extracting method for high frequency components of
      abnormal intra-QRS of exercise ECG signal].
AB  - This article introduces a method of extracting high frequency components of
      abnormal intra-QRS of exercise ECG signal by using spline function interpolation
      algorithm, and defines QRSe of the residual signal as quantitative index. Some
      expected results have been obtained. This method is an effective measuring
      approach to further researches on the high frequency components of exercise and
      other ECG signals.

PMID- 10879195
TI  - [QRS detection based on neural-network].
AB  - In this paper, we have developed an adaptive matched filtering algorithm based
      upon an artificial network (ANN) for QRS detection. We used an ANN adaptive
      whitening filter to model the lower frequencies of the ECG signals which are
      inherently nonlinear and non-stationary. The residual signal which contained
      mostly higher frequency QRS complex energy was then passed through a linear
      matched filter to detect the location of the QRS complex. The results demonstrate
      that this ANN whitenting filter is very effective for removing the time-varying,
      nonlinear noise characteristic of ECG signals. With this novel approach, the
      detection rate for a very noisy patient record in the MIT/BIH arrhythmia database
      in 99.2%, which compares favorably to the 97.8% achieved with a band-pass
      filtering method.

PMID- 10879196
TI  - [Effects of extremely low frequency weak magnetic fields on the intracellular
      free calcium concentration in PC-12 tumor cells].
AB  - In this study the effects of the extremely low frequency (ELF) magnetic fields on
      intracellular Ca2+ concentration ([Ca2+]i) of rat chromaffinoma PC-12 cells were
      examined by using a digital fluorescence image microscopy system. A 50 Hz, 100
      microT sinusoidal ELF magnetic field increased [Ca2+]i to a marked level, whereas
      a static field or a field of higher frequency (2000 Hz) did not cause a [Ca2+]i
      increase. The magnetic field-induced [Ca2+]i rise was partly due to an influx of
      extracellular Ca2+ and partly due to the release of intracellular Ca2+ pool. It
      seemed likely that the Ca2+ transport ability of the cell membranes was increased
      by the 50 Hz magnetic field.

PMID- 10879197
TI  - [Remodeling and biomechanical properties of thoracic aorta in spontaneously
      hypertensive rats].
AB  - Morphometry and microstructure of thoracic aorta of spontaneously hypertensive
      rats (SHR) at different periods before and after hypertension were studied
      quantitatively by histological method and computer image analysis. We also
      observed the changes of opening angle in the zero-stress state and the
      relationship between pressure and diameter in SHR during established
      hypertension. The results showed that with blood pressure chronically increasing,
      there was a significant increase in morphometric parameters and microstructure
      parameters of the thoracic aorta in SHR. The zero-stress state of opening angle
      in SHR during established hypertension increased significantly. These reults
      suggest that aortic structural remodeling in hypertension such as thickness of
      vascular wall and disproportional increase of collagen may lead to decrease in
      distensibility of the aorta in SHR. The structural remodeling and changes of
      mechanical properties in aorta may contribute to the important pathophysiology of
      hypertension-induced complications.

PMID- 10879198
TI  - [A study of ventricular repolarization duration variability and dependence of
      RTm/RR].
AB  - As an important electrophysiological parameter that reflects cardiac
      depolarization and repolarization process, ventricular repolarization duration
      has been drawing growing attention. It is influenced by several physiological and
      pathological factors and associated with several cardiac diseases. We studied
      repolarization duration variability (RDV) and dependence of RTm/RR among normal
      subjects of different age-groups, as well as between normal subjects and subjects
      with cardiac diseases. It was found that RDV and dependence of RTm/RR are related
      to age. There are significant differences in the slope of RTm/RR, coherence, CV
      ratio and RDV between normal subjects and subjects with cardiac diseases. The RDV
      and dependence of RTm/RR can be employed in providing a more useful evaluation of
      cardiac disease and function in clinical care.

PMID- 10879199
TI  - [Progress in the field of tissue engineering].
AB  - Tissue engineering is a new field in biomedical engineering. In this review,
      progress in the field of tissue engineering is presented in detail, including a
      general introduction, design and fabrication principles, key technologies,
      various applications, new directions, as well as related market and R&D issues.

PMID- 10879200
TI  - [Latest progress in studies of self-setting calcium phosphate cement].
AB  - Self-setting calcium phosphate cement(CPC) is a non-ceramic form of
      hydrxyapatitic artificial bone material (HAP) which was first exclusively
      produced in America several years ago. CPC is free from the drawbacksto ceramic
      HAP, including sintering and difficulties in shaping. CPC has the characteristics
      of simple-producing and easy applyication. In 1991, the clinical application of
      CPC to repairing the calvarial bone defects was approved, and the results
      reportedly so far were good or excellent. This paper presents the latest progress
      in the studies of CPC, concerning the probing into the setting process, the
      producing of fast-setting and non-decayed types of CPC, the studies of organic
      compound CPC, the in vitro results of CPC as a drug delivery system, etc. As the
      research goes on deeply and broadly, CPC is hopefully becoming a standard
      material in repairing bone defects at the non- or low-bearing site in the future.

PMID- 10879201
TI  - [Researches on surface modification for prevention of bacterial adhesion to
      implanting biomaterials].
AB  - The failure of operation caused by biomaterials centered infections (BCI) has
      seriously restricted the clinical application of biomaterials. Two mechanisms of
      bacterial adhesion and the relationship between surface free energy of
      bimaterials and bacterial adhesion are introduced and discussed in this paper.
      Increasing the surface free energy can improve (decrease) the adhesion of some
      kinds of bacteria. At last, some methods of the surface modification are
      reviewed.

PMID- 10879202
TI  - [The use of insulin as carrier in targeted therapy].
AB  - Upon insulin binding to its receptor, the receptor-ligand complexes will be
      internalized into the target cell. The internalized insulin will leave the
      endosome and associate with the nuclear matrix. This process might be useful for
      targeted therapy. Some complex can link with the insulin be internalized into the
      target cell by insulin receptor-mediated endocytosis and enter the cell nuclei to
      cure some diseases.

PMID- 10879203
TI  - [Plasma technology for biomedical material applications].
AB  - In this paper is introduced the plasma technology for the applications of several
      species biomaterial such as ophthalmological material, drug delivery system,
      tissue culture material, blood anticoagulant material as well as plasma surface
      clearing and plasma sterilization, and so on.

PMID- 10879204
TI  - [Theories of pulse wave in arteries].
AB  - This paper introduces the importance of studying pulse wave propagation and
      neviews the development process of the theories of pulse wave propagation. The
      main research achievements of nonlinear theories of pulse wave propagation are
      described, and the developing directions of studying pulse wave propagation are
      briefly stated.

PMID- 10879205
TI  - [Progress of study on selectin].
AB  - Selectin is a member of vascular adhesion molecular family. Selectin can mediate
      the interaction between endothelial cell and leucocyte, therefore, it is an
      important factor in infectious disease, transplantation immunity, development of
      tumor, vascularization, ischemia-reperfusion injury and autoimmune disease. In
      this report, selectin's molecular structure, function, expression, regulation and
      gene reformation were discussed.

PMID- 10879206
TI  - [Development of a control and monitor system for the cardiopulmonary cerebral
      resuscitation(CPCR) device].
AB  - A novel idea in developing cardiopulmonary-cerebral resuscition(CPCR) device has
      been developed, using a combination of membrane artificial lung(oxygenator), mild
      hypothermia, and centrifugal blood pump technologies. A control system for the
      CPCR has been introduced, using converter control and sensor monitor, with 8031
      chips as the controller. Pressure, flow rate and temperature monitors were
      installed in the system. Two modes of blood pump regulation have been adopted,
      i.e. continous flow and pulsatile flow. The in vitro evaluation tests showed that
      the two modes were reasonable and feasible.

PMID- 10879207
TI  - [A self-adaptable system for acquiring and processing animal ECG parameters].
AB  - The present authors have developed a computerized system for acquiring and
      processing the animal ECG. The system provides many functions in the software
      design and the users can compile the parameter-analyzing formulae by themselves
      according to the characteristics of ECG. The system is much more accurate and
      flexible in analyzing the ECG parameters and can significantly avoid the
      processing mistakes caused by signal variations and interference. It is
      especially suitable for continuous ECG monitoring and analysis of animal
      experiments in physiology, pharmacology and toxicology.

PMID- 10879208
TI  - [Research on the parameters of Mark V injector].
AB  - This study sought to correctly preset the parameters of Mark v injection. The
      emphasis was laid on the flow rate in that, it ought to be set more carefully and
      more accurately for ensuring success in angiography. The authors analyzed the
      influential factors of flow rate and the relationship between flow rate and
      pressure limiting and hence proposed a set of typical presetting injection
      parameters. Experimental results demonstrated that with the contrast media
      concentration around 75%, high quality images could be obtained by setting the
      pressure limiting within 2068-5515 kPa.

PMID- 10879209
TI  - Community care management across the continuum. Study results from a Medicare
      health maintenance plan.
AB  - A large national health plan piloting a community care management (CCM) model for
      its high-risk, chronically ill, Medicare population has demonstrated a
      significant reduction in overall medical costs for its participants. The key
      elements include: the proactive identification and risk stratification of
      members; assignment of advanced practice nurses to physicians with high-volume
      high-risk members; and ongoing clinical management across the continuum,
      establishing a continuous relationship with the member. The results are derived
      from a retrospective study comparing 6 months of claim data prior to the member
      entering CCM, with 6 months of claim data while participants received community,
      care management. Members in the pilot study experienced both a 42% reduction in
      institutional days and a 53% reduction in admissions to acute care settings. In
      addition, physician and specialists fees were reduced by 37%. This resulted in a
      6-month net savings of $3,602 per participant. To be extremely conservative, the
      savings were reduced by 50% to reflect the possible impact of regression to the
      mean. Even accounting for this, the program's projected cost savings are $1,801
      per participant in 6 months. The total projected savings for community care
      managed members in a fully implemented program divided by the entire enrolled
      population of 27,000 is $6.60 per member per month (PM/PM). The results of this
      study of care management across the continuum signal a new approach for medical
      management at a time when health care and the needs of the population are
      changing.

PMID- 10879210
TI  - Iowa Case Management for rural drug abuse. Preliminary results.
AB  - The Iowa Case Management Project (ICMP) was developed to evaluate the
      effectiveness of a comprehensive, solution-focused model of case management with
      rural clients in drug abuse treatment. For this preliminary report, 483 clients
      who were admitted to residential or outpatient treatment at a local facility
      volunteered to participate and were randomly assigned to one of four research
      conditions. Clients in three of the conditions received Iowa Case Management
      (ICM), while clients in the fourth condition received standard treatment services
      and served as the control group. Clients were assessed regarding psychosocial
      characteristics at intake and three additional times during the subsequent 12
      months.

PMID- 10879211
TI  - The importance of a nurse case manager, a personal assistant, and a strong
      support system. A case scenario.

PMID- 10879212
TI  - Home health care regulation. Is it good for the patient?

PMID- 10879213
TI  - Public policy out of control. The home health care experience.
AB  - The home health care delivery system is facing challenges that threaten its
      survival as well as its very essence. Currently, the federal government provides
      the threat of disaster for home care patients, staff, and organizations. The
      dangers are palpable and very real. Although the immediate survival threat is
      fiscal, there are two other areas which have the potential to be equally
      devastating. The first is reduced, in some instances absent, patient access to
      care at home. The second is the flight of professional and paraprofessional
      personnel from home care.

PMID- 10879214
TI  - The financial burdens of the Balanced Budget Act of 1997.
AB  - The Balanced Budget Act of 1997 (BBA) was signed into law on August 5, 1997 as
      Public Law No. 105-33. This single act introduced a revolutionary phase for the
      health care industry in the United States. It marked the beginning of momentous
      change to the overall health care coverage provided through the Medicare program.
      These changes, contained in the Balanced Budget Act, were intended to reduce
      substantially Medicare reimbursement, primarily to postacute care providers,
      including Certified Home Health Agencies. As a matter of fact, the Federal
      Register of August 5, 1999 states that "the intent of Section 4602 of the BBA is
      to control the soaring expenditures of the Medicare home health benefit that have
      been driven largely by increased utilization rather than price per visit."

PMID- 10879215
TI  - Issues of financial pressure on home care agencies. Dealing with the potential of
      fiscal abuse.

PMID- 10879216
TI  - Racial characteristics of human teeth with special emphasis on the Mongoloid
      dentition.
AB  - Determining the racial affinity of an unknown individual from dentition for
      identification is indeed a difficult endeavour. However, there are certain dental
      characteristics which are predominant in certain racial groups and these
      contribute important indicators in the identification process. Inherited dental
      characteristics are modified by prenatal and postnatal environmental and
      nutritional conditions. They can also become less discernible due to admixture of
      the various races.

PMID- 10879217
TI  - Emerging problems of antibiotic resistance in community medicine.
AB  - Emergence of antimicrobial resistance in bacteria associated with community
      acquired infections has made the choice of empirical therapy more difficult and
      more expensive. The problems due to possible spread of MRSA to the community,
      emergence of penicillin resistance in S. pneumoniae, ampicillin resistance in H.
      influenzae, and multiresistance among common enteric pathogens are highlighted.
      Bacteria have a remarkable ability to develop resistance to many of the newly
      synthesized antimicrobial agents but the appropriate use of antibiotics will
      delay and in many cases prevent the emergence of resistance.

PMID- 10879218
TI  - Group A streptococcal infections.

PMID- 10879219
TI  - Mycobacterial infection.

PMID- 10879220
TI  - Commercialization of health services: implications for the laboratories.
AB  - The commercialization of health services has wide ranging implications for all
      medical specialties as well as for patients. Factors that must be considered
      include not only the financial implications, but also questions of quality and
      academic interests such as teaching and training. Laboratories must provide a
      service that the purchaser wishes to buy and must be successful in overcoming
      competition from the private sector. Each component part of the overall service
      must be analyzed in order that the laboratory is efficiently structured to
      provide an optimum service. A good understanding of management issues and a
      flexible approach are paramount in the provision of efficient, cost-effective and
      quality service for the ultimate benefit of the patient.

PMID- 10879221
TI  - Comparison of two monoclonal antibody kits with cell culture isolation in the
      detection of respiratory virus antigens.
AB  - Two different preparations of monoclonal antibodies developed against respiratory
      viruses have been evaluated by the immunofluorescence antibody technique. The
      Chemicon monoclonal antibodies were found to be more efficient at picking up
      positive specimens with a high sensitivity and specificity than Imagen monoclonal
      antibodies. However, the overall concordance rate of the monoclonal antibodies
      was 92.3%-100%. Generally, when compared with cell culture isolation, the
      immunofluorescence antibody technique was found to be more sensitive. The high
      quality of the Chemicon monoclonal antibodies contribute to their value in
      providing definitive diagnosis, within a few hours of specimen collection, thus
      allowing early management of patients, their contacts and control of hospital
      infection.

PMID- 10879222
TI  - Evaluation of the use of Bactec anaerobic blood cultures in the detection of
      bacteraemia and fungaemia in children.
AB  - In an attempt to reduce costs, the role of Bactec anaerobic blood culture in the
      detection of bacteraemia and fungaemia in children was evaluated. Results from
      3167 sets of aerobic and anaerobic blood cultures from children admitted to the
      University Hospital, Kuala Lumpur during a one year period, were analysed. Four
      hundred and eight (12.9%) sets of blood cultures were positive, of which 348 sets
      (11.0%) from 201 patients were clinically significant. Of the 348 significant
      positive sets, organisms were isolated on 177 (50.9%) occasions from both aerobic
      and anaerobic bottles, on 136 (39.1%) occasions from the aerobic bottle only and
      35 (10.0%) occasions from the anaerobic bottle only. No strict anaerobes were
      isolated, but clinically significant isolates recovered from the anaerobic bottle
      only included Klebsiella pneumoniae, Salmonella species, Enterobacter cloacae,
      Staphylococcus aureus, coagulase negative staphylococci, Streptococcus pneumoniae
      and Group B streptococcus. Patients with bacteraemia diagnosed solely by
      anaerobic culture were distributed evenly across the various paediatric
      subspecialities. When results from the anaerobic bottles were excluded, the
      overall isolation rate was reduced from 11% to 9.9%. Potential financial savings
      resulting from omission of anaerobic cultures must be balanced against the small
      number of bacteraemic episodes that could be missed. Undiagnosed bacteraemia may
      result in increased morbidity and mortality with its own attendant financial
      implications.

PMID- 10879223
TI  - Nucleolar organizer regions distribution in fine needle aspiration cytological
      smears from breast lesions.
AB  - Fine needle aspiration (FNA) cytology is now an integral part of the pre
      operative investigation of breast lesions and the therapeutic protocol is today
      often planned on the basis of cytodiagnosis. However, from time to time the
      cytological picture may be equivocal or inconclusive. In recent years, nucleolar
      organizer region (NOR) scores have been explored for potential value in the
      diagnosis of malignancy as the scores in malignant nuclei are seen to be higher
      than in benign or reactive nuclei. With a view to applying NOR scoring in the
      evaluation of cytologically equivocal cases, we adopted the argyrophil technique
      for staining NOR s (AgNOR) in FNA cytological smears of 56 breast lesions,
      comprising 31 benign and 25 malignant lesions. Histological correlation was
      possible in 26 of these cases (17 malignant and 9 benign) and AgNOR scoring was
      done on paraffin sections of these as well. There was a significant difference
      between mean AgNOR scores in benign and malignant lesions in the cytological
      smears (P < 0.001). The AgNOR scores ranged from 2.5 to 5.0 per cell in benign
      lesions and 5.8 to 17.2 per cell in malignant lesions. None of the cases fell
      into the gray zone of overlap. One malignant lesion that was cytologically
      equivocal showed a mean AgNOR score of 6.08. The AgNOR scores on histological
      sections also showed a statistically significant difference (P < 0.001) between
      benign and malignant lesions with mean scores ranging from 1.34 to 2.58 dots per
      cell in benign lesions and scores of 2.42 to 5.28 dots per cell in malignant
      lesions. However, the scores overlapped in four cases and therefore it was
      considered unsuitable for routine diagnostic work. From this preliminary study,
      we conclude that an FNA AgNOR score of 5.0 and less strongly favours a benign
      lesion whereas a score above 5.0 would be in favour of a malignant lesion. A
      larger study would be needed to verify our impression that AgNOR scoring can be
      useful in cytologically equivocal cases.

PMID- 10879224
TI  - Usefulness and limitations of an in-house direct radioimmunoassay for 17
      hydroxyprogesterone in serum.
AB  - Since conventional radioimmunoassays (RIA) for measurement of 17
      hydroxyprogesterone (17-OHP) in serum samples require a laborious solvent
      extraction step, a direct and rapid in-house RIA was developed for early
      diagnosis and management of congenital adrenal hyperplasia (CAH). In-house rabbit
      anti-17-OHP antiserum, tritium labelled 17-OHP and dextran-coated charcoal were
      used in assay buffer with low pH 5.1 and preheated serum samples. Both inter- and
      intra-assay CVs were < 10% and the sensitivity was 1.2 nmol/l or 12 fmol/tube.
      Results from the direct assay correlated well with values from an extraction
      assay, r = 0.88 in samples from CAH patients, r = 0.85 in adults and children,
      0.69 and 0.40 in term and preterm neonates respectively, 0.66 and 0.63 in luteal
      phase and third trimester pregnancy; p < 0.001 in all groups except p < 0.05 in
      preterm neonates. However, results from the direct assay were two to three times
      higher in serum samples from CAH patients, normal adults and children, but were
      five to seven times higher in pregnancy and term neonates and thirty times higher
      in preterm neonates. The markedly elevated levels measured by the direct assay
      are probably due to cross-reactivities with water-soluble steroid metabolites
      such as 17-hydroxypregnenolone sulphate and dehydroepiandrosterone sulphate
      (DHEAS). Although the direct assay is only useful as a screening test for preterm
      babies, it can be used for both diagnosis and monitoring of treatment of CAH in
      all other age groups.

PMID- 10879225
TI  - Measurement of androstenedione levels by an in-house radioimmunoassay.
AB  - An in-house radioimmunoassay (RIA) for the measurement of androstenedione levels
      in serum was established and validated. Levels of androstenedione were measured
      by RIA using serum samples from various normal population groups and patients
      with congenital adrenal hyperplasia (CAH). Analytical recovery and linearity
      results were > 95%, while intra- and inter-assay CVs were < 10% and < 22%
      respectively. The assay sensitivity was 0.5 nmol/l or 25 fmol/tube. In normal
      population groups, the highest androstenedione levels were found in preterm
      neonates (1.6-12.4 nmol/l), followed by adult females (1.5-10.2 nmol/l), adult
      males (1.6-8.0 nmol/l) and term neonates (0.8-8.8 nmol/l), while the lowest
      values were observed in prepubertal children (0.5-3.4 nmol/l). There were no
      significant differences in diurnal variation and between follicular and luteal
      phases. The range of androstenedione levels in untreated or poorly controlled CAH
      patients (7.6-355.0 nmol/l, median 42.5 nmol/l, n = 20) were significantly higher
      (p < 0.001) than the upper normal limit of 3.4 nmol/L for prepubertal children.
      The normal androstenedione reference ranges for paediatric and adult groups have
      thus been established.

PMID- 10879226
TI  - Presence of pro-opiomelanocortin peptides and corticotropin-releasing factor in
      human placenta.
AB  - Immunoreactive adrenocorticotropin (ACTH), beta-endorphin (BEP) and corticotropin
      releasing factor (CRF) were detected in human term placenta obtained from
      elective Caesarian surgery. The concentrations of ACTH, BEP and CRF in placenta
      detected by radioimmunoassay (RIA) were 2.83 +/- 0.36, 0.52 +/- 0.05 and 0.56 +/-
      0.15 ng/g wet weight of tissue respectively. Pro-opiomelanocortin (POMC) peptides
      were also detected in the amnion and chorion membranes and in the decidua. The
      concentrations of ACTH were 1.72 +/- 0.20, 4.43 +/- 0.39 and 5.80 +/- 0.17 ng/g
      and the levels of BEP were 0.42 +/- 0.18, 0.65 +/- 0.20 and 3.66 +/- 1.10 ng/g in
      the amnion, chorion and decidua respectively. In contrast to placenta,
      immunoreactive CRF was not detected in the amnion, chorion and decidua.
      Immunoreactive N-acetylated BEP was also not detected in all the placental
      subfractions. Comparison of the amounts of both ACTH and BEP in the various
      placental components indicated the following distribution: decidua > chorion >
      placenta > amnion. In decidua, POMC peptides were present in an equi-molar ratio
      but in the other three placental fractions, ACTH levels were three to five-fold
      higher than BEP. In immunohistochemical studies, only a positive staining for
      ACTH was obtained for decidua. Our results confirm the presence of POMC peptides
      and CRF in placenta and their physiological roles in pregnancy and parturition.

PMID- 10879227
TI  - Cytological analysis of breast lesions: a review of 780 cases.
AB  - 780 breast cytology samples obtained over a one year period at the Breast Clinic
      of the University Hospital, Kuala Lumpur were reviewed. These included 745 fine
      needle aspirates (FNA's) and 35 nipple smears. The broad categories of
      cytodiagnoses were as follows: malignant: 95, suspicious or equivocal: 26,
      benign: 543, no proliferative lesion: 58 and inadequate: 58. The benign and
      malignant lesions were also subcategorized on cytological basis. The suspicious
      or equivocal lesions were subjected to biopsy and 17 of these proved to be
      malignant. 194 cases that were subjected to histological confirmation and 34
      cases that were considered to be undisputably malignant (on the basis of clinical
      features, recurrences, metastases, etc.) were subjected to statistical analysis
      (total 228 cases). If the cytologically suspicious/equivocal category was
      considered as "test positive" the sensitivity of cytodiagnosis was 97.4% and the
      specificity 92%. The high degree of cytodiagnostic sensitivity and specificity
      make breast cytology a valuable adjunct in the evaluation of breast lesions.

PMID- 10879228
TI  - Application of the Serodia-HCV particle agglutination for the detection of
      antibodies to hepatitis C virus.
AB  - The Serodia-HCV Particle Agglutination (HCV-PA) for the detection of HCV
      antibodies was compared with the Enzyme Immunoassay Test (UBI HCV EIA) for
      possible in-house use. A total of 150 specimens were analysed using UBI HCV EIA
      and Serodia-HCV PA. Of these, 80 (53.3%) were both PA and EIA positive and 59
      (39.3%) were negative by both techniques. Eleven sera (7.4%) were found to be EIA
      positive but PA-negative. These 11 discordant sera were further tested by the
      LiaTek-HCV III Immunoassay (Organon Teknika). Ten were found to be line
      immunoassay negative and one was line immunoassay positive. Failure of the PA to
      detect the HCV positive serum meant that a small proportion of HCV antibody
      positives may be missed by the PA test. We conclude that (i) EIA should continue
      to be the first line screening test in our laboratory, (ii) PA with its 100%
      specificity could be a useful supplementary screen for all EIA-positive sera and
      finally (iii) line immunoassay could be used on sera to resolve discordant
      results in the EIA and PA assays.

PMID- 10879229
TI  - The value of liver function tests in hepatocellular carcinoma.
AB  - This study was undertaken to see if liver function tests (LFT) served a
      worthwhile purpose in the investigation of hepatocellular carcinoma (HCC). Sera
      from 80 HCC, 76 benign liver disease (BLD) and 152 healthy adult (HA) subjects
      were assayed for alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT),
      aspartate aminotransferase (AST), alanine aminotransferase and lactate
      dehydrogenase, bilirubin and albumin. Cut-off values were determined from the HA.
      ALP, GGT, AST and albumin were abnormal in about 90% of the HCC. With the
      exception of bilirubin, the LFT were abnormal more frequently in HCC than in
      chronic hepatitis and cirrhosis, the conditions which preceed it. Raised ALP in
      the presence of normal bilirubin was more often a feature of HCC than BLD
      although this relationship was not statistically significant. It seems unlikely
      that LFT serve a useful function in HCC.

PMID- 10879230
TI  - Surfactant protein A and stable microbubble formation in tracheal aspirates.
AB  - This study aimed to determine the role of surfactant protein A (SP-A) in the
      formation of stable microbubble in tracheal aspirates. Our results showed that as
      the concentration of anti SP-A antibodies added to tracheal aspirate specimens
      increased, the number of stable microbubble formed in the specimen decreased. The
      correlation between stable microbubble counts and the SP-A levels in the tracheal
      aspirates was good, r = 0.85, p < 0.05. This study suggests that SP-A plays an
      important role in stable microbubble formation. Measurement of small stable
      microbubbles is thus a useful bedside test for predicting the SP-A activity in
      the tracheal aspirates and in indirect measurement of lung maturity.

PMID- 10879231
TI  - Efficiency of blood usage for elective surgery in the University Hospital Kuala
      Lumpur.
AB  - Provision of quality care, service and blood products to patients while
      containing costs and the amount of blood used should be the aim of every blood
      bank. Therefore a prospective audit was carried out over three months to
      determine how efficiently blood was being used in elective surgery in the
      University Hospital, Kuala Lumpur. Every case with blood crossmatched was
      monitored to determine the amount transfused and the posttransfusion haemoglobin
      level. Overcrossmatching of varying degrees was noted in almost all surgical
      procedures and overtransfusion in 45.5% of patients transfused. The rate of case
      postponement was 18.1%. These indicate inefficient utilization of blood and other
      resources. The transfusion index (TI) and range of units transfused were
      calculated for each procedure. They can be used as indicators of blood
      requirement and potential severity of hemorrhage. Suggestions to improve
      efficiency of blood utilization include the introduction and ongoing monitoring
      of guidelines on crossmatching and transfusion based on the data obtained here,
      by the hospital blood transfusion committee; the "group, screen and hold"
      practice for surgical procedures with high crossmatch transfusion ratios, low
      transfusion indices and a small range of units transfused could also be adopted.

PMID- 10879232
TI  - Tumours and tumour-like lesions of the eye: a clinicopathological study from
      Hospital University Sains Malaysia.
AB  - A total of 89 histopathologically proven ocular tumours and tumour-like lesions
      treated in Hospital University Sains Malaysia, Kubang Kerian, Kelantan over a
      period of nine years were reviewed for their age distribution, site of lesion and
      histological type. The tumours were observed in all age groups with a maximum
      prevalence in the first decade. Twenty lesions were malignant and 69 were benign.
      The eyelid was the most frequent location (51%), followed by the conjunctiva
      (32%). Retinoblastoma was the most common malignant tumour (10 cases) and dermoid
      cyst was the most common tumour-like lesion (16 cases).

PMID- 10879233
TI  - Adrenal cytomegaly associated with diaphragmatic hernia: report of a case.
AB  - A rare case of a 22-week-old foetus with unilateral adrenal cytomegaly and left
      diaphragmatic hernia is reported. Typical cytomegalic cells were found focally in
      the left adrenal but the right adrenal was normal. There was no stigmata of the
      Beckwith-Wiedermann syndrome. The association of adrenal cytomegaly with various
      congenital malformations, the significance and possible pathogenesis of this
      condition is discussed.

PMID- 10879234
TI  - Recovery of forensically important insect larvae from human cadavers in Malaysia
      (1993-1996).
AB  - Forensically important entomological specimens recovered from 95 forensic cases
      of human cadavers from April 1993 to May 1996 in Malaysia were identified and
      analysed. The results indicated that 73.7% of these specimens were Chrysomya
      species, occurring either as single or mixed infestations. Of these, the most
      prominent species were Ch megacephala (F.) and Ch rufifacies (Macquart). Other
      fly maggots recovered included Sarcophaga spp., Lucilia spp. and Hermetia spp.,
      mostly occurring together with other calliphorine flies. A member of Muscidae
      fly, Ophyra spp. was also recovered for the first time.

PMID- 10879235
TI  - Molecular genetics and prenatal diagnosis of the thalassaemias.

PMID- 10879236
TI  - An approach to the investigation of thrombophilia.

PMID- 10879237
TI  - Bone metabolism: newer perspectives.
AB  - The general perception of bone is that of an inert material which provides the
      framework (skeleton) to support the rest of the body and organs. This concept is
      totally inaccurate. Bone is in fact a vital organ of the body. Structural
      stability only happens to be one of its many important functions. Bone is a
      dynamic connective tissue. Among the functions of bone are: (1) support of
      mechanical loads, (2) protection of vital organ, (3) haematopoiesis, (4) ionized
      mineral homeostasis, (5) regulation of tissue development, remodeling and repair
      through the synthesis of paracrine and autocrine factors, and (6) electrical
      capacitors. Cellular interaction between the 3 cell types and hormonal, physical
      and chemical signals controls bone health. The osteoblasts appear to communicate
      with the osteocytes and osteoclasts both directly and indirectly and coordinates
      cell activity. Mineral metabolism is a well recognised function of bone. However
      bone biomechanics and electrical function are little appreciated activities of
      bone.

PMID- 10879238
TI  - Postmenopausal osteoporosis: epidemiology, pathophysiology and treatment.

PMID- 10879239
TI  - Steroid-induced osteoporosis--a cause for concern?

PMID- 10879240
TI  - Correlation between histological grade and c-erbB2 oncoprotein overexpression in
      infiltrating ductal carcinoma of breast.
AB  - One hundred and twelve infiltrating ductal carcinoma of breast were studied by
      the standard avidinbiotin complex immunoperoxidase method on formalin-fixed,
      paraffin-embedded tissue sections, using a monoclonal antibody to c-erbB-2
      oncoprotein. The same tumours were assessed and scored according to the Bloom and
      Richardson criteria into three histological grades. The distribution of tumours
      according to grade were: 8 Grade I, 34 Grade II and 70 Grade III. Forty-three
      (38.4%) tumours showed positive membrane staining for c-erbB-2 oncoprotein. These
      comprised 7 Grade II and 36 Grade III tumours with c-erbB-2 immunopositivity
      rates of 20.6% and 51.4% respectively. The oncoprotein was not expressed by Grade
      I tumours. This study shows a good correlation between c-erbB-2 expression and
      histological grade, a known prognostic indicator of invasive breast carcinoma.
      Because the c-erbB-2 oncogene has extensive structural homology to the epidermal
      growth factor receptor gene, its overexpression can be expected to result in more
      aggressive tumour behaviour. While it may be regarded as another indicator of
      poor prognosis breast cancers, its value in the selection of carcinomas less
      responsive to hormonal therapy and those more suitable for immunotherapy than
      chemotherapy has been mooted but remains to be clarified.

PMID- 10879241
TI  - Antibody responses of dengue fever patients to dengue 2 (New Guinea C strain)
      viral proteins.
AB  - The present study was undertaken to investigate the antibody responses of dengue
      fever (DF) patients to specific dengue virus proteins. Partially purified dengue
      2 New Guinea C (NGC) strain virus was used as antigen. Under the present
      experimental protocols, it was observed that almost all DF patients' sera had
      detectable presence of antibodies which recognize the dengue 2 envelope (E)
      protein. The convalescent-phase sera especially had significant detectable IgG,
      IgM and IgE against the protein. In addition, IgGs specific against the NS1 dimer
      and PrM were also detected. Antibody against the core (C) protein, however, was
      not detectable in any of the DF patients' sera. The substantial presence of IgG
      against the PrM in the convalescent-phase sera, and the presence of IgE specific
      for the E, reflect the potential importance of these antibody responses in the
      pathogenesis of dengue.

PMID- 10879242
TI  - Comparison of alpha-fetoprotein with some other tumour markers in Malaysians with
      hepatocellular carcinoma.
AB  - Although alpha-fetoprotein (AFP) is regarded as the reference marker for
      hepatocellular carcinoma (HCC), it sometimes produces false results. The
      objective of this study was to see if some of the readily available laboratory
      markers could complement AFP to improve the laboratory diagnosis of HCC. The
      markers tested and their sensitivities were: CA 125, 92%; ferritin, 71.3%; CA 19
      9, 69.8%; beta-2-microglobulin (B2M), 53.3%; CA 72-4, 13.6%; and carcinoembryonic
      antigen (CEA), 10.6%. In comparison, AFP had a sensitivity of 58.8%. CA 72-4 and
      CEA (at the "tumour" cut-off level of 20 ng/ml) had specificities of 100%, and
      AFP, 97.4%. The specificities of the other markers were less impressive: CEA,
      77.8% (at the cut-off level of 5 ng/ml); ferritin, 48.6%; CA 125, 48.5%; B2M,
      39.6%; and CA 19-9, 37.3%. The efficiencies of the markers for HCC, which are
      based on the consideration of sensitivity and specificity together, were as
      follows: AFP, 77.6%; CA 125, 71.3%; ferritin, 60.5%; CA 19-9, 55.3; B2M, 46.9%;
      CEA, 40.8%; and CA 72-4, 34.5%. The receiver-operating characteristic plots
      confirmed AFP to be the most efficient marker for HCC. Nevertheless, it is
      proposed that CA 125 be combined with AFP for HCC screening because of their
      excellent sensitivity and specificity, respectively: a negative result for both,
      or even just CA 125 alone, would indicate that the disease is unlikely while a
      positive AFP (which would likely occur with a positive CA 125) would make its
      presence highly probable. A positive CA 125 and negative AFP would be equivocal
      for HCC. Other markers in combination with AFP are less useful.

PMID- 10879243
TI  - The pattern of Ki-67 and bcl-2 expression in lymphoid malignancies.
AB  - The International Working Formulation divides non-Hodgkin's lymphoma (NHL) into
      three grades: low, intermediate and high. This grading system implies rate of
      tumour growth and hence prognosis. Ki-67 antigen is a proliferation-related
      nuclear antigen and bcl-2 oncogene product is known to inhibit apoptosis. This
      study aimed to determine the pattern of expression of Ki-67 antigen and bcl-2
      oncoprotein in various grades of NHL. Paraffin-embedded tissues from 42 cases of
      NHL (7 low, 15 intermediate, 20 high grade) were retrieved from the files of the
      Department of Pathology, University of Malaya. Ki-67 antigen and bcl-2
      oncoprotein were detected using immunohistochemistry. The percentage of
      positively stained neoplastic cells was determined by semi-quantitative
      estimation and given scores ranging from 0 to 6. Partition chi square test
      demonstrated the association of Ki-67 antigen expression and histological grade
      (p = 0.007). There was no significant difference in Ki-67 antigen expression
      between intermediate and high grade malignant lymphomas (p = 0.28), whereas
      significant difference was demonstrated between low and intermediate/high grade
      tumours (p = 0.003). Bcl-2 oncoprotein expression in the neoplastic cells varied
      widely within the three histological grades. Statistical analysis showed no
      association between the expression of bcl-2 oncoprotein and histological grade (p
      = 0.25). Ki-67 immunostaining is therefore a useful adjunct to histological
      grading of NHL.

PMID- 10879244
TI  - An evaluation of the usefulness of a culture system for the detection of
      Ureaplasma urealyticum in the endotracheal aspirates of neonates.
AB  - In this study, we evaluated the usefulness of a culture system used in our
      laboratory for the detection of Ureaplasma urealyticum in the endotracheal
      aspirates of neonates. Ureaplasmal broth was used to enhance the growth of U.
      urealyticum followed by observation of colonies on A7 agar. Of the 68 samples of
      endotracheal aspirates tested, 60 gave positive indication of urease activity by
      the broth. However, only 14 yielded U. urealyticum colonies on A7 agar medium.
      Polymerase chain reaction detected U. urealyticum in 21 samples. The use of
      Ureaplasmal broth was therefore not specific for the diagnosis of U. urealyticum.
      We suggest that subculture onto agar medium or PCR is essential for definite
      identification of U. urealyticum.

PMID- 10879245
TI  - Fine needle aspiration cytology of secretory carcinoma of breast: a case report.
AB  - A 39-year-old female presented with a mobile 1.5 cm nodule in the right breast.
      Fine needle aspiration cytology smears stained with May Grunwald Giemsa were
      highly cellular with a monotonous population of dissociated and clustered tumour
      cells that showed a bland cytological appearance with cytoplasmic vacuolation and
      occasional signet ring forms. Intracellular and extracellular mucus was present.
      Histological study of the excised breast mass showed a secretory carcinoma. This
      is a rare breast neoplasm in which cytological features are characteristic enough
      to permit a specific diagnosis on needle aspirates.

PMID- 10879246
TI  - Publication bias and the Medical Editors Trial Amnesty.

PMID- 10879247
TI  - Seeking representation in policy-making governmental bodies.

PMID- 10879248
TI  - The business man and the laboratory: standards guarantee profits.

PMID- 10879249
TI  - The importance of the medico-legal autopsy.
AB  - All deaths due to unnatural causes and deaths that are believed to be due to
      natural causes but where the medical cause of death is not certain or known are
      subjected to an inquest. The objective of an inquest is to ascertain facts
      pertaining to the death. This is achieved by inquiry and at the conclusion of the
      inquest a verdict is arrived as to whether the death was due to a natural,
      accidental, suicidal or a homicidal cause. An inquest is not a trial. There is no
      complainant or defendant and at the conclusion of the inquest no judgment is
      passed. The inquest system exists in all parts of the world. In the English legal
      system, the person who conducts an inquest is called a Coroner. In Scotland, he
      is called a Procurator Fiscal. The United States of America use the Medical
      Examiner system. Most continental European countries and their former colonies
      follow the Code Napoleon. A postmortem examination may become necessary in
      certain deaths that come up for inquests. In these situations the authority which
      conducts the inquest will order a doctor to perform a postmortem examination
      (medico-legal autopsy). To perform a medico-legal autopsy, consent from the
      relatives of the deceased is not required. In an unexpected sudden death, only a
      doctor after a postmortem examination may be able to determine the cause of
      death. However, it is often wrongly assumed that the objective of a postmortem
      examination is only to ascertain the cause of death. This article deals with the
      purpose of the inquest and roles of the medico-legal autopsy.

PMID- 10879250
TI  - Confidentiality and death.
AB  - The duty of confidentiality in the normal doctor-patient relationship is well
      recognized. However, the duty of confidentiality between the pathologist who
      performs the autopsy and the requesting authorities and the next-of-kin is not as
      clearly spelt out. This article discusses the problems faced by the pathologist
      with regards to hospital and medico-legal autopsies in Malaysia. A proposed
      ethical guideline is included on how to deal with peculiar issues regarding
      confidentiality and the pathologist.

PMID- 10879251
TI  - Enhanced major histocompatibility complex (MHC) class II antigen expression in
      lupus nephritis.
AB  - Thirty-eight cases of lupus nephritis, all satisfying the American Rheumatism
      Association criteria for diagnosis of systemic lupus erythematosus (SLE), with
      renal involvement and biopsy were immunohistochemically studied for the
      expression of HLA-DR (DAKO: HLA-DR/alpha, TAL.1B5), one of the three known
      families belonging to the class II major histocompatibility complex (MHC), using
      a standard streptavidin-biotin-peroxidase method. 20 nephrectomies performed for
      renal trauma and tumours constituted the normal controls. Of the lupus nephritis
      cases, 34 were females and 4 males. Ethnically, 20 were Chinese, 13 Malay, 4
      Indian and 1 of indigenous origin. Their ages ranged from 16 to 59 years (mean of
      31 years). Histologically, 23 expressed World Health Organisation (WHO) class IV
      (diffuse proliferative), 10 WHO class V (diffuse membranous), 4 WHO class II
      (pure mesangiopathy) and 1 WHO class III (segmental and focal proliferative)
      nephritis. Activity scores ranged between 5 to 19 (mean = 8.6) and chronicity
      scored between 2 to 7 (mean = 3.2) on a standard scoring system. Similar to other
      studies, HLA-DR was expressed in the glomerular capillaries and peritubular
      capillaries of all and mesangium, tubules (proximal, distal and collecting),
      veins and arterioles of some normal controls. Interestingly, HLA-DR expression
      was noted in the arteries of 25% of the normal controls, a finding hitherto not
      reported. The frequency of lupus nephritis cases expressing HLA-DR in the various
      anatomical components did not differ significantly from the normal controls
      except that HLA-DR expression in arteries and arterioles was seen at a
      significantly increased frequency (p < 0.01) in lupus nephritis. This increased
      expression did not correlate with the WHO class, activity or chronicity scores.
      It therefore appears that MHC class II shows increased expression in the arterial
      system of lupus nephritis kidneys. The significance of this is unclear but could
      be related to heightened (gamma-interferon activation which may be a de novo
      phenomenon or result of T cell proliferation and activation in SLE.

PMID- 10879252
TI  - Lymphocyte subsets in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by
      increased B cell activity and depressed T cell function. However, the
      contribution of the immunoregulatory system to its pathogenesis is still unclear.
      The recent development in the production of monoclonal antibodies and the
      availability of bench-top flow cytometers have allowed rapid quantitation of
      peripheral blood lymphocyte subsets. We analysed the distribution of the
      lymphocyte subsets in 24 patients with active SLE and 18 with inactive SLE. The
      distribution of immunoregulatory cells in 72 normal volunteers was used as
      control. Statistical analysis showed that there were significant differences
      between both the SLE groups and the normal controls, for total lymphocytes, T
      cells, B cells, T helper cells, T suppressor cells, T helper/suppressor ratio and
      natural killer cells. There was a significant difference for T helper cells
      between active and inactive SLE. T helper cells levels were found to be low in
      inactive SLE and lower in active SLE. It appears that treatment-induced
      remissions did not restore the levels of immunoregulatory cells to normal. Thus,
      T helper cell levels reflect disease activity and longitudinal assays of T helper
      cells may serve as an indicator of disease reactivation.

PMID- 10879253
TI  - Detection of Chlamydia trachomatis in urine samples by polymerase chain reaction
      and enzyme immunoassay.
AB  - First-void urine samples collected from sexually transmitted diseases (STD)
      clinic patients were examined by a nested polymerase chain reaction (PCR) and a
      commercial enzyme immunoassay (IDEIA Chlamydia) for the diagnosis of Chlamydia
      trachomatis urethritis or cervicitis. The primers for the PCR amplified a target
      in the major outer membrane protein (MOMP) gene in C trachomatis while the IDEIA
      detected genus-specific chlamydial lipopolysaccharide. Discrepant results were
      resolved by retesting urine specimens with a second (plasmid-based) PCR and
      taking urethral or endocervical swab results into consideration. For 231 men
      (chlamydial prevalence 20.4%), the sensitivity, specificity, positive and
      negative predictive values were 59.6%, 99.5%, 96.6% and 90.6% for urine IDEIA,
      68.1%, 99.5%, 97% and 92.4% for urethral swab IDEIA and 97.9%, 99.5%, 97.9% and
      99.5% for urine PCR. The corresponding rates for 66 women (chlamydial prevalence
      54.6%) were 19.4%, 100%, 100% and 50.8% for urine IDEIA, 86.1%, 96.7%, 96.9% and
      85.3% for endocervical swab IDEIA and 91.7%, 93.3%, 94.3% and 90.3% for urine
      PCR. Hence, in a high prevalence population, the urine IDEIA was a suitable
      alternative to the male urethral swab IDEIA but significantly less sensitive than
      the endocervical swab IDEIA. The urine PCR was, however, much more sensitive than
      the urine IDEIA for both men and women and could replace the endocervical swab
      IDEIA for the diagnosis of chlamydial cervicitis.

PMID- 10879254
TI  - Detection of false positives by incorporation of a confirmatory blocking test
      into a commercial enzyme-linked immunosorbent assay specific for adenovirus
      antigen.
AB  - A blocking test was incorporated into the commercial IDEIA Adenovirus test (DAKO
      Diagnostics Ltd., Cambridgeshire, UK) to detect false positive results when
      faecal specimens were tested for adenovirus antigen. Immune rabbit serum raised
      against pooled adenovirus particles from human faecal specimens, together with
      the pre-immune serum, was used. Assessment of positive showed that false
      positives were produced under two different conditions: when results were based
      on visual determination instead of a cut-off value determined from photometric
      reading, and when absorbance values were not immediately read at the end of the
      test. Under the optimum condition for reading and assessment of test results
      (immediate reading and photometric determination), 11% of 65 adenovirus-positive
      samples were checked by the blocking ELISA as false positives. The rest of the
      specimens showed blocking of positive absorbance values by 70 to 98%. ELISA was
      found to be more sensitive than immune electron microscopy on samples with lower
      antigen concentration.

PMID- 10879255
TI  - Methanol as an alternative fixative for cytological smears.
AB  - Ninety-five percent (95%) ethanol is the standard cytological fixative used in
      many laboratories. Commercially available ethanol is expensive and not freely
      available in some institutions. Methanol, a tissue dehydrant, is also known to be
      a cytological fixative. However its efficacy has not been assessed or documented
      in the literature. One hundred and eight consecutive fine needle aspiration
      biopsies (FNAB) of thyroid performed at the Department of Pathology, Faculty of
      Medicine, Colombo were included in a study to assess the efficacy of methanol as
      a cytological fixative. Aspirated material was smeared on at least 2 slides, one
      fixed in ethanol and the other in methanol, and stained with haematoxylin and
      eosin (H&E). The 2 smears were separately assessed for preservation of colloid
      and cells (nuclei and cytoplasm), as determined by the staining quality with the
      H&E stain. A score was given for each smear and the final scores for ethanol and
      methanol were statistically compared. The evaporation rates for ethanol and
      methanol were calculated. The total score for preservation of colloid was 294/300
      (98%) for methanol and 291/300 (97%) for ethanol (p = 0.4). The total score for
      preservation of cells (nuclear and cytoplasmic) was 276/279 (98.9%) for methanol
      and 274/279 (98.2%) for ethanol (p = 0.7). The evaporation rates per 100 ml when
      the bottles used for fixation were kept closed and open per 24 hours were 1 and
      37 for methanol and 0 and 17 for ethanol. Literature search did not show
      inhalational side effects of methanol in humans under standard laboratory
      conditions. We conclude that methanol is as effective as ethanol for fixation of
      smears and cheaper.

PMID- 10879256
TI  - Uniform requirements for manuscripts submitted to biomedical journals, and
      additional statements, 1997. International Committee of Medical Journal Editors.

PMID- 10879257
TI  - Biology and pathological associations of the human papillomaviruses: a review.
AB  - Historical cottontail rabbit papillomavirus studies raised early indications of a
      mammalian DNA oncogenic virus. Today, molecular cloning recognises numerous
      animal and human papillomaviruses (HPVs) and the development of in vitro
      transformation assays has escalated oncological research in HPVs. Currently,
      their detection and typing in tissues is usually by Southern blotting, in-situ
      hybridization and polymerase chain reaction methods. The complete papillomavirus
      virion constitutes a protein coat (capsid) surrounding a circular, double
      stranded DNA organised into coding and non-coding regions. 8 early (E1-E8) open
      reading frames (ORFs) and 2 late (L1, L2) ORFs have been identified in the coding
      region of all papillomaviruses. The early ORFs encode proteins which interact
      with the host genome to produce new viral DNA while late ORFs are activated only
      after viral DNA replication and encode for viral capsid proteins. All
      papillomaviruses are obligatory intranuclear organisms with specific tropism for
      keratinocytes. Three possible courses of events can follow papillomaviruses entry
      into cells: (1) viral DNA are maintained as intranuclear, extrachromosomal,
      circular DNA episomes, which replicates synchronously with the host cell,
      establishing a latent infection; (2) conversion from latent into productive
      infection with assembly of complete infective virions; (3) integration of viral
      DNA into host cellular genome, a phenomenon seen in HPV infections associated
      with malignant transformation. Human papillomaviruses (HPVs) essentially induce
      skin and mucosal epithelial lesions. Various skin warts are well known to be HPV
      associated (HPVs 1, 2, 3, 7 and 10). Besides HPVs 3 and 10, HPVs 5, 8, 17 and 20
      have been recovered from Epidermodysplasia verruciformis lesions. Anogenital
      condyloma acuminatum, strongly linked with HPVs 6 and 11 are probably sexually
      transmitted. The same HPVs, demonstrable in recurrent juvenile laryngeal
      papillomas, are probably transmitted by passage through an infected birth canal.
      HPVs described in uterine cervical lesions are generally categorized into those
      associated with high (16, 18), intermediate (31, 33, 35, 39, 45, 51, 52, 56, 58,
      59, 68) and low (6, 11, 26, 40, 42, 43, 44, 53, 54, 55, 62, 66) risk of cervical
      squamous carcinoma. Cervical adenocarcinoma, clear cell carcinoma and small cell
      neuroendocrine carcinoma have also been linked to HPVs, especially HPV18. Other
      lesions reported to be HPV-associated are: papillomas, dysplasia and carcinomas
      in the nasal cavity (HPV 6, 11, 57); squamous papilloma, condyloma acuminatum,
      and verruca vulgaris of the oral cavity (HPV 6, 11), oral focal epithelial
      hyperplasia (HPV 13, 32); warty lip lesions (HPV 2): and conjunctival papillomas
      (HPV 6, 11).

PMID- 10879258
TI  - Cellular proteins bind to the 3' and 5' untranslated regions of dengue 2 virus
      genome.
AB  - In vitro generated cloned full length dengue 2 virus untranslated regions (UTRs)
      were used in RNA gel mobility shift assays to examine cellular factors binding to
      the virus genomes. Cellular factors in lysates of Vero (monkey) and C6/36
      (mosquito) cells bound specifically and non-specifically to the dengue 2 virus 3'
      UTR. Non-specific interaction with the 5' UTR, resulting in formation of at least
      4 band shift complexes was noted with lysate of the C6/36 cells only. Pre
      treating the cell lysates with proteinase K affected binding of cellular factors
      to the dengue 2 virus UTRs, suggesting that the cellular factors were proteins.
      These findings suggest that cellular proteins could interact with specific sites
      on the dengue virus genomes.

PMID- 10879259
TI  - C-erbB-2 oncoprotein amplification in infiltrating ductal carcinoma of breast
      relates to high histological grade and loss of oestrogen receptor protein.
AB  - Eighty-six infiltrating ductal carcinoma of breast were studied by the standard
      avidin-biotin complex immunoperoxidase method on formalin-fixed, paraffin
      embedded tissue sections, for oestrogen receptor (ER) protein and c-erbB-2
      oncoprotein expression. They were categorized according to the modified Bloom and
      Richardson criteria into three histological grades. 21% tumours were ER positive
      while 44% were c-erbB-2 positive. Of ER positive tumours, 33.3% were c-erbB-2
      positive whereas the c-erbB-2 positivity rate was much higher (47.1%) in ER
      negative tumours. Only 16% of c-erbB-2 positive tumours were ER positive while
      25% of c-erbB-2 negative tumours were ER positive. This negative relationship
      between ER and c-erbB-2 expression was statistically significant (Mc Nemar's
      test, p < 0.005). The ER positivity rate did not vary significantly with
      histological grade. However, c-erbB-2 overexpression was significantly more
      prevalent in grade III tumours compared with grade I and II tumours (Chi-square
      test, p < 0.005). Since the c-erbB-2 oncogene has extensive structural homology
      to the epidermal growth factor receptor (EGFR) gene, we expect that c-erbB-2
      oncoprotein would share functional similarities with EGFR leading to both loss of
      oestrogen receptor and poor prognosis in breast cancer. Its overexpression can be
      expected to relate to more aggressive tumour proliferation and may explain its
      correlation with high histological grade, a known indicator of aggressive cancer
      behaviour. As there is no indication that ER protein activity contributes to
      advancement in histological grade, it would appear that cellular
      dedifferentiation precedes ER loss during malignant transformation. It has been
      mooted that ER positive breast cancers which also show c-erbB-2 oncoprotein
      overexpression have a poorer response to hormonal therapy. The use of this
      parameter in the routine assessment of breast cancer patients may identify
      subsets of patients for more aggressive therapy.

PMID- 10879260
TI  - Rotavirus electropherotypes from the Kuala Lumpur Hospital: a re-examination
      after an interval of seven years.
AB  - The objective of this study was to ascertain the extent changes have occurred in
      the epidemiology of human rotavirus electropherotypes from the same location 7 to
      8 years after an earlier study. Genomic RNA profiles of rotaviruses from
      diarrhoeic children admitted to the Kuala Lumpur Hospital from April to December
      1996 were determined by polyacrylamide gel electrophoresis and silver staining. A
      total of 179 group A rotaviruses were detected from 870 children: 175 with
      legible staining of all RNA segments were classified into 14 distinct
      electropherotypes (10 and 4 with long and short migration patterns respectively).
      In addition, the results revealed: high predominance of long pattern
      electropherotypes (94% of the total electropherotypes); most long
      electropherotypes with RNA profiles which all 11 RNAs migrated separately (8 of
      10 electropherotypes); all short electropherotypes had segments 2 and 3 that co
      migrated; presence of a very numerically dominant electropherotype (75% of all
      electropherotypes); frequent co-circulation of the dominant electropherotype
      present throughout the study period--with other electropherotypes present for
      limited periods; sequential temporal appearances by similar electropherotypes.
      These observations were similar to that of an earlier study conducted in 1988/89.
      Nevertheless, the dominant electropherotype in the present study was different
      and not among the electropherotypes detected in the earlier study.

PMID- 10879261
TI  - Evaluation of the cholera spot test: a chromatographic immunoassay for the rapid
      detection of cholera antigen.
AB  - A chromatographic immunoassay cholera antigen detection kit, the Cholera Spot
      test, was evaluated. The test was found to be specific with a sensitivity of
      10(6) cfu/ml for the direct detection of V. cholerae in simulated stool specimens
      and 10 cfu/ml in simulated cotton-tipped swab specimens after overnight
      incubation in alkaline peptone water. This enables early recognition of cholera
      cases and their contacts so that prevention and control measures can be promptly
      instituted.

PMID- 10879262
TI  - A clinical audit on the practice of platelet transfusions at a tertiary
      paediatric referral centre.
AB  - Platelet transfusions are indicated in a wide variety of clinical conditions
      especially those with thrombocytopenia. However, without proper clinical practice
      guidelines, inappropriate transfusions are bound to happen. To ascertain the
      provision of a quality and appropriate practice of platelet transfusions, an
      audit study was carried out over a period of one month at the Paediatric
      Institute, Kuala Lumpur Hospital. A prospective audit was performed during that
      period whilst a retrospective collection of data was carried out for the previous
      month for comparison. Based on a set of criteria agreed upon by the audit
      committee, it was found that in 18.5% (22 of 119) of the cases, the indications
      for platelet transfusions were inappropriate. The audit committee concluded that
      there is a need for a more detailed clinical practice guideline for local use to
      reduce or lower the incidence of inappropriate transfusions of platelets.

PMID- 10879263
TI  - Angiosarcoma of the breast complicating pregnancy.
AB  - A 32-year-old pregnant lady presented with a rapidly enlarging right breast mass.
      A fine needle aspiration was suggestive of a malignant phylloides tumour. However
      histopathological examination after mastectomy revealed a moderately
      differentiated angiosarcoma. The histopathological and cytological features of
      this rare tumour together with the diagnostic pitfalls are discussed.

PMID- 10879264
TI  - Mucoepidermoid carcinoma of the thyroid: a case report.
AB  - Primary mucoepidermoid carcinoma (MEC) of thyroid is an uncommon tumour and
      reports on its' cytology are consequently scanty. A 46-year-old male presented
      with a thyroid nodule of nine months duration. Fine needle aspiration (FNA)
      cytology of the nodule showed features of a malignant tumor that was different
      from the usual types of thyroid carcinoma. Monolayers and syncytial clusters of
      round and spindle tumour cells with large vesicular nuclei and single
      macronucleoli were present. A diagnosis of carcinoma was given with the comment
      that this was unlike any of the usual types of thyroid cancer and that a
      metastatic malignancy should be ruled out. The cytological picture of MEC may not
      always be distinctive enough for accurate tumour typing. Nevertheless the
      cytological features are usually sufficiently different to rule out all of the
      usual types of thyroid carcinoma. This distinction may be important from the
      point of view of differing prognosis in MEC of thyroid (as compared to
      differentiated thyroid cancers) and the need to exclude a metastatic carcinoma,
      especially from a primary in one of the salivary glands.

PMID- 10879265
TI  - Sudden death during jungle trekking: a case of heat stroke.
AB  - Heat stroke, which is also known as "sun stroke," is a medical emergency, and
      fatalities can occur unless it is diagnosed early and treated efficiently. Heat
      stroke may manifest quite suddenly, giving little time to differentiate it from
      extreme physical exhaustion in collapsed subjects. It is also known to lead to
      serious disseminated intravascular coagulation. Sudden death in a young female is
      presented who collapsed after trekking in a hilly, jungle area in Malaysia on a
      warm, humid day. She had joined a weight reduction programme a few weeks earlier.
      She was found collapsed and in a semiconscious state in the jungle by her
      groupmates and was taken to hospital. On admission she was unconscious,
      hyperpyrexic, with rapid, thready pulse and a low blood pressure. Biochemical
      studies revealed metabolic acidosis, elevated liver and cardiac enzymes and
      impairment of renal function. Her coagulation profile was found to be impaired
      and she started bleeding through the mouth and nostrils. She also developed
      watery diarrhoea and initially a septicaemic condition, including acute enteritis
      was suspected. Despite active treatment, her condition deteriorated and she died
      eight hours after admission. Autopsy confirmed a generalised bleeding tendency,
      with pulmonary, oesophageal and gastrointestinal mucosal haemorrhages. Flame
      shaped subendocardial shock haemorrhages were seen in the interventricular septum
      on the left side of the heart. The findings support a diagnosis of heat stroke.
      Various aspects related to heat stroke, the autopsy diagnosis and its prevention
      are discussed.

PMID- 10879266
TI  - Outbreak of fatal childhood viral infection in Sarawak, Malaysia in 1997: inocula
      of patients' clinical specimens induce apoptosis in vitro.
AB  - Identification of the aetiologic agent(s) associated with an outbreak of fatal
      childhood viral infection in Sarawak, Malaysia, in mid 1997 remains elusive. It
      is reported here that African green monkey kidney (Vero) and human monocytic
      (U937) cells treated with inocula derived from clinical specimens of some of
      these fatal cases showed the presence of cellular genomic DNA degradation when
      the extracted DNA was separated by pulsed field gel electrophoresis (PFGE),
      oligonucleosomal DNA ladders characteristic of apoptotic cells when the infected
      cells' DNA was separated by agarose gel electrophoresis, and apoptotic cellular
      DNA fragmentation when cells were stained using terminal deoxynucleotidyl
      transferase (TdT)-mediated dUTP nick-end labeling (TUNEL). These results suggest
      that inocula derived from the patients' clinical specimens contain factors which
      stimulate apoptotic cellular responses in vitro.

PMID- 10879267
TI  - An enzyme immunoassay for advanced glycosylation end-products in serum.
AB  - We successfully developed an in-house, competitive enzyme immunoassay to measure
      advanced glycosylation end-products (AGE) in serum. The assay involved coating
      microtitre wells with AGE-BSA at 8 micrograms/ml for 4 hours, followed by
      overnight incubation of 20 microliters sample (prediluted at 1:6) with 80
      microliters antiserum (1:8000). HRP-labelled goat anti-rabbit was used as the
      second antibody and 3,5',5,5'-tetramethylbenzidine dihydrochloride as the
      substrate. Incubation was carried out at 4 degrees C. As suggested in an earlier
      study, we standardised the AGE units against normal human serum (NHS). Thus, one
      AGE unit was defined as the inhibition that resulted when the 1:6 diluted NHS was
      assayed. Mean (+/- SD) AGE level in normal subjects (n = 37) was significantly
      lower than in diabetes subjects with microalbuminuria (n = 57) (6.0 +/- 0.7
      versus 10.2 +/- 4.7 units/ml, p = 0.0001). With the availability of in-house
      assay and by standardising the AGE unit with the other laboratories, more studies
      could be undertaken and results compared, and possibly, further elucidate the
      roles of AGE in the pathogenesis of diabetic complications.

PMID- 10879268
TI  - Flow cytometric analysis of intracellular myeloperoxidase distinguishes
      lymphocytes, monocytes and granulocytes.
AB  - A study was undertaken to evaluate the ability of flow cytometric analysis of
      intracellular myeloperoxidase (MPO) in differentiating populations of lymphocytes
      (L), monocytes (M) and granulocytes (G), by means of lysed whole blood method.
      Anticoagulated blood from 23 normal individuals was lysed with FACS lysing
      solution and permeabilized with FACS permeabilizing solution before subjected to
      direct immunofluorescence staining. The geometric means of the fluorescence
      intensity were measured using FACSCalibur flow cytometer (Becton Dickinson).
      Populations of L, M and G were gated based on their light scatter characteristics
      and expression of CD14 and CD45. Then, the fluorescence intensity of MPO
      expression was studied in these individual cell populations. The results showed
      that fluorescence intensity of MPO was the strongest in G and weakest in L,
      whereas M showed intermediate fluorescence intensity. Our findings reveal that
      discrimination of these three cell types is achievable based upon the sole
      expression of intracellular MPO.

PMID- 10879269
TI  - Detection of Legionella pneumophila antigens in patients' sera using monoclonal
      antibodies.
AB  - Three monoclonal antibodies (McAb) were produced against soluble antigens of
      Legionella pneumophila serogroup 1 which was cultured on BCYE agar. The McAbs
      were all of the IgM isotype. The McAbs were used in the McAb-based ELISA for
      detection of circulating L. pneumophila antigens in 186 sera collected from
      patients with symptoms and signs suggestive of atypical pneumonia. The normal
      reference optical (OD) density value of each of the McAbs was determined using 44
      sera collected from healthy blood donors. The antigen positivity rates for the
      McAbs 1C7.2B, 2B2.10F and 2B2.11E were 11.3%, 7.7% and 22.2% respectively.
      Antigen positivity of the McAb 2B2.10F was significantly higher in the younger
      age group (p < 0.05). There is no significant association between the antigen
      positivity with age and sex for all the McAbs. There was no cross-reaction
      demonstrated between the McAbs with other bacterial antigens.

PMID- 10879270
TI  - The usefulness of limited placental sampling in stillbirths.
AB  - 144 placentas were sampled from all cases of stillbirth weighing 500 g and above
      seen over a period of thirteen months in the UKM Unit of the Maternity Hospital,
      Kuala Lumpur. Sampling was limited to 1-3 blocks per placenta for histological
      study. Placental abnormalities were found in 121 (85%) placentas, 78 of which had
      definite lesions known to contribute to foetal death while the remainder showed
      lesions suggestive of an underlying disease. This study supports the usefulness
      of limited sampling of the placenta in the face of unavailability of complete
      placental examination and autopsy for assessment of the cause of stillbirth.

PMID- 10879271
TI  - Serum ferritin and lactate dehydrogenase in a case of hemophagocytic
      lymphohistiocytosis.
AB  - A 40-day-old baby girl presented with intermittent fever, lymphadenopathy,
      massive hepatosplenomegaly, progressive pancytopenia and features of disseminated
      intravascular coagulopathy. A bone marrow aspiration was performed and showed
      florid histiocytic proliferation with marked hemophagocytosis. Based on the
      diagnostic guideline for Hemophagocytic Lymphohistiocytosis proposed by the
      Familial Hemophagocytic Lymphohistiocytosis Study Group of Histiocyte Society,
      this patient has fulfilled most of the criteria. We have also found that serum
      ferritin and lactate dehydrogenase to be very high in this patient. It remains
      uncertain whether the disorder is reactive or neoplastic.

PMID- 10879272
TI  - Primary squamous cell carcinoma of the thyroid--a case report.
AB  - A rare case of primary squamous cell carcinoma of the thyroid is reported herein.
      A 64-year-old Malay lady presented with a gradually enlarging thyroid nodule for
      the past 6 months and underwent total thyroidectomy. Histopathology revealed a
      squamous cell carcinoma of the thyroid with complete resection. Possible primary
      tumour elsewhere was excluded. Postoperative irradiation was given and patient is
      still alive after 2 years of follow-up.

PMID- 10879273
TI  - Incidence of acute atherosis in complete molar pregnancy.
AB  - A clinicohistological study of acute atherosis in molar pregnancy was undertaken.
      Maternal decidual vessels in currettage samples of 38 histologically confirmed
      complete hydatidiform moles were examined histologically for acute atherosis,
      recognised as fibrinoid necrosis of the smooth muscle wall with a perivascular
      mononuclear cell infiltrate, with or without lipophages. Acute atherosis was
      detected in eight of 38 cases, an incidence of 18.4%. All the patients were
      normotensive. The significance of acute atherosis in molar pregnancy remains to
      be clarified.

PMID- 10879274
TI  - Carcinoma of the uterine cervix: a review of its pathology and commentary on the
      problem in Malaysians.
AB  - Since its recognition about 150 years ago, there has been much progress in the
      understanding of the pathogenesis, prevention, early detection and management of
      carcinoma of the uterine cervix. Important historical landmarks include the (1)
      recognition of pre-invasive and pre-clinical lesions, and the devise of various
      systems for reporting these lesions, (2) improvements in diagnostic techniques
      particularly colposcopy, (3) advent of therapeutic procedures
      (electrocoagulation, cryotherapy, laser therapy and loop electrosurgical
      excision), and (4) recognition of the aetiological relationship between the human
      papillomavirus and cervical neoplasia. The susceptibility of the cervical
      transformation zone to malignant change is now well recognised. The WHO
      classification system remains the one most commonly utilised for histological
      reporting of cervical cancers. In the recent 1994 update, cervical carcinoma is
      divided into 3 main categories: squamous cell carcinoma, adenocarcinoma and other
      epithelial tumours. Squamous cell carcinoma (60-80%) predominates among invasive
      cervical carcinoma. Recognised variants include verrucous, warty (condylomatous),
      papillary squamous (transitional) and lymphoepithelioma-like carcinoma.
      Adenocarcinoma (5-15% of invasive carcinomas) shows an increasing trend in young
      females. Like its squamous counterpart, preinvasive and microinvasive versions
      are known. Variants such as mucinous, endometrioid, clear cell, mesonephric,
      serous, villoglandular and minimal deviation carcinoma are now defined.
      Adenosquamous carcinoma (5-25%), adenoid-cystic, adenoid-basal, neuroendocrine
      and undifferentiated carcinomas constitute other epithelial tumours of the
      cervix. The management of invasive cervical carcinoma remains heavily dependent
      on its stage. The FIGO staging system remains the most widely used. The 1995
      update provides more definite criteria in subdividing stage IA tumours by
      delimiting stromal invasion of stage IA1 lesions to a maximum depth of 3 mm and a
      horizontal axis of 7 mm. In Malaysia, an appreciation of the cervical carcinoma
      problem has to take into consideration the population at risk, its multi
      ethnicity, its socio-economic and geographical diversities and the constraints of
      the health care system. Females form 48.9% of the Malaysian population. 52.9% of
      them are in the sexually active age group of 15-50 years, indicating a
      significant population at risk for cervical carcinoma. Cervical carcinoma was the
      third most common cause of death due to solid tumours among Malaysian females in
      1995 following carcinoma of the breast and respiratory tract. East Malaysia is
      predominantly rural with many communities having limited modern facilities. Such
      areas imply a lower educational and socio-economic status, raising the worry of a
      population at higher risk for developing cervical carcinoma. The population:
      doctor for Malaysia of 2153:1 compares poorly with nearby Singapore. Besides a
      shortage of doctors, there is also an uneven distribution of doctors, resulting
      in a ratio in East Malaysia of > 4000:1. Although Malaysia does not have a
      national cervical cancer-screening programme, many action plans and cancer
      awareness campaigns have been launched throughout the years, which appear to have
      made an impact as evidenced by the decreasing mortality rates from cervical
      carcinoma. Another interesting feature of cervical carcinoma in Malaysia relates
      to its multiethnic population. In Malaysian Chinese and Malay females, the
      prevalence of cervical carcinoma ranks second to breast cancer whereas the
      pattern is reversed in Malaysian Indian females. Studies into its aetiology and
      pathogenesis are being undertaken and may shed more light on this matter.

PMID- 10879275
TI  - Fine needle aspiration cytology of the thyroid--a review of experience in 1853
      cases.
AB  - 1853 thyroid lesions subjected to cytological sampling (either by the fine needle
      aspiration or fine needle capillary sampling technique) from January 1992 to
      December 1997 at the University Hospital, Kuala Lumpur, were reviewed. Nodular
      goitre was the most common thyroid lesion needled (67.35%). Among the neoplastic
      lesions, follicular neoplasms predominated (64%), followed by papillary carcinoma
      (29.4%). In 325 cases, partial or total thyroidectomy had been done, providing
      material for histological review and cyto-histological correlation. Cytological
      diagnosis was found to have high sensitivity and specificity rates of over 75%.
      Besides, most non-neoplastic thyroid lesions could be diagnosed on cytology. The
      scope of cytology in the diagnosis of lymphomas, anaplastic and metastatic
      tumours rendered diagnostic biopsies (or thyroidectomy) unnecessary in these
      cases. Being a cost-effective technique and having the capacity to provide exact
      morphological diagnosis in a large variety of thyroid lesions, cytology is
      obviously the method of choice in the assessment of thyroid nodules.

PMID- 10879276
TI  - The pattern of amyloid deposition in the lung.
AB  - A review of routine histopathological samples and autopsies examined at the
      Department of Pathology, University of Malaya revealed 15 cases of amyloidosis of
      the lung. Two were localized depositions limited to the lung while in the
      remainder, lung involvement was part of the picture of systemic amyloidosis. Both
      cases of localized amyloidosis presented with symptomatic lung/bronchial masses
      and a clinical diagnosis of tumour. Histology revealed "amyloidomas" associated
      with heavy plasma cell and lymphocytic infiltration and the presence of
      multinucleated giant cells. In both cases, the amyloid deposits were
      immunopositive for lambda light chains and negative for kappa chains and AA
      protein. One was a known systemic lupus erythematosus patient with polyclonal
      hypergammaglobulinaemia. The other patient was found to have plasma cell
      dyscrasia with monoclonal IgG lambda gammopathy. Both patients did not develop
      systemic amyloidosis. In contrast, lung involvement in systemic AA amyloidosis
      was not obvious clinically or macroscopically but was histologically evident in
      75% of cases subjected to autopsy. Amyloid was detected mainly in the walls of
      arterioles and small vessels, and along the alveolar septa. It was less
      frequently detected in the pleura, along the basement membrane of the bronchial
      epithelium and around bronchial glands. In one case of systemic AL amyloidosis
      associated with multiple myeloma, an "amyloidoma" occurred in the subpleural
      region reminiscent of localized amyloidosis. These cases pose questions on (1)
      whether localized "tumour-like" amyloidosis is a forme fruste of systemic AL
      amyloidosis and (2) the differing pattern of tissue deposition of different
      chemical types of amyloid fibrils, with the suggestion that light chain amyloid
      has a greater tendency to nodular deposition than AA amyloid.

PMID- 10879277
TI  - Comparative analysis of three permeabilization methods for cytofluorometric
      evaluation of cytoplasmic myeloperoxidase.
AB  - A comparative study was conducted to evaluate three different permeabilization
      methods: FACS Permeabilizing Solution (FPerm), CytoFix/CytoPerm Kit (CFP) and
      Paraformaldehyde-Tween 20 (PFT) reagents, in cytoplasmic labeling of
      myeloperoxidase (MPO). Peripheral blood cells from 23 healthy subjects were fixed
      and permeabilized according to the proposed procedures, prior to direct
      immunofluorescence staining with CD14, CD45, IgG1, IgG2 and MPO monoclonal
      antibodies (McAb). Subsequent flow cytometric analysis was performed on
      FACSCalibur flow cytometer (Becton Dickinson, BD). As far as the antigenic
      expression of MPO in normal samples is concerned, FPerm and CFP demonstrated
      better cytoplasmic staining by inducing minor effects on light-scattering
      properties of the cell populations, whereas PFT-treated samples showed a
      diminished ability to distinguish the cell types. However, the simple and rapid
      FPerm method required an earlier processing of samples since the stored whole
      blood samples (for more than 8 hours) tended to show a significant decrease of
      fluorescence intensity. We also have demonstrated that P/N ratio possesses added
      value in evaluation of cell reactivity in immunophenotyping, based upon the
      apparent nonspecific cytoplasmic staining of MPO in the lymphocyte population.

PMID- 10879278
TI  - The pattern of lymphoma in east Malaysian patients as experienced in the
      University Hospital, Kuala Lumpur.
AB  - Lymphoma is a highly heterogeneous group of malignant disease. This study aimed
      to elucidate the pattern of lymphoma in the East Malaysian patient population.
      107 cases of confirmed lymphomas from East Malaysian biopsy material were
      retrieved from the files of the Department of Pathology, University of Malaya, in
      the 3-year period between 1981 to 1983. With the use of a panel of lymphoid
      antibodies, the disease was sub-classified using the Rye classification for
      Hodgkin's lymphoma (HL) and the REAL classification for non-Hodgkin's lymphoma
      (NHL). All of the cases were tested for the presence of the Epstein-Barr virus by
      EBER-ISH. There were 11 (10.3%) HL, 80 (74.7%) B-NHL and 16 (15%) T-NHL. The
      HL:NHL ratio was 1:9. The most common tumour in children was Burkitt's lymphoma
      7/13 (53.8%). In the adult group, there were 72/94 (76.6%) B-NHL ?diffuse large
      cell type 51 (of which 2 were CD30+), Burkitt's lymphoma 8, follicular lymphoma
      5, low grade MALT 2, mantle cell type 1 and not otherwise specified due to poor
      morphology 5?, 13/94 (13.8%) T-NHL and 9/94 (9.6%) HL. Of the 9 adult HL, the
      most common subtype was nodular sclerosis (6, 66.7%). The EBER positive rate in
      classical HL, T-NHL, BL and B-NHL were 33.3%, 56.3%, 60.0% and 3.1% respectively.
      In conclusion, the spectrum of lymphoma seen in East Malaysia was rather similar
      to West Malaysia except for the very low prevalence of peripheral T-cell lymphoma
      (PTCL) in Sarawak (3.3%).

PMID- 10879279
TI  - Effects of glycyrrhizic acid and steroid treatment on corticotropin releasing
      factor and beta-endorphin containing neurons of the hypothalamus of the rat.
AB  - Corticotrophin releasing factor (CRF) and beta-endorphin (beta EP) containing
      neurons are shown to be present in the hypothalamus and both neurons are found at
      the paraventricular nucleus (PVN). Steroid hormones have been found to alter the
      plasma level of these neurotransmitters. Glycyrrhizic acid (GCA) is the active
      component of liquorice. GCA inhibits the enzyme 11 beta-hydroxysteroid
      dehydrogenase (11HSD) which is needed for the inactivation of the steroid
      pathway, so therefore would cause changes to these neurons. The aim of this study
      was to investigate the effects of GCA as well as deoxycorticosterone (DOC) and
      dexamethasone (DM) on the modulation of CRF and beta EP containing neuron at the
      PVN of the hypothalamus. Rats were given either DM, DOC or GCA and
      adrenalectomized (ADX) and given either DM or DOC. At the end of treatment rats
      were transfused transcardially before sacrifice and the brain were dissected for
      immunohistochemical analysis. We found that immunostaining of the CRF containing
      neurons demonstrate a reduction in the number of positive neurons in DM treated
      rats. DOC and GCA treated rats showed the same result as in DM rats but the
      reduction is less. ADX, DM, DOC and GCA treated rats did not show any changes in
      the number of beta EP containing neurons but naloxone increased the number of
      beta EP containing neurons markedly. In conclusion, GCA and DOC have similar
      effects on CRF and beta EP containing neurons at the PVN.

PMID- 10879280
TI  - Immunotactoid glomerulopathy--an unusual deposition disease: report of the first
      Malaysian case.
AB  - A 31-year-old Malay female presented with nephrotic syndrome without renal
      impairment. Renal biopsy features were in keeping with immunotactoid
      glomerulopathy (ITG). Non-Congophilic deposits were seen causing thickening of
      the glomerular capillary basement membrane with segmental accentuation, and
      widening of the mesangium. Immunofluorescence examination showed moderate amounts
      of IgG and C3 in the glomerular capillary walls with some in the mesangium.
      Ultrastructurally, 20-nm thick fibrils with microtubular organisation were
      present predominantly in the subendothelial region with similar fibrils in the
      mesangium. Although immunotactoid glomerulopathy and fibrillary
      glomerulonephritis (FG) have been recognised as entities with extracellular
      fibrillary material in the kidney, to date much remains to be clarified regarding
      these 2 conditions. While the renal biopsy findings in this patient are
      consistent with ITG, her clinical presentation is unlike that of usual ITG in
      that she is of a much younger age and has no associated haemopoietic disorder.
      Response to initial treatment of 8 weeks of prednisolone therapy was poor.

PMID- 10879281
TI  - Exploiting the immune system: toward new vaccines against intracellular bacteria.

PMID- 10879282
TI  - The cytoskeleton in lymphocyte signaling.

PMID- 10879283
TI  - TGF-beta signaling by Smad proteins.
AB  - Members of the transforming growth factor-beta (TGF-beta) family bind to type II
      and type I serine/threonine kinase receptors, which initiate intracellular
      signals through activation of Smad proteins. Receptor-regulated Smads (R-Smads)
      are anchored to the cell membrane by interaction with membrane-bound proteins,
      including Smad anchor for receptor activation (SARA). Upon ligand stimulation, R
      Smads are phosphorylated by the receptors and form oligomeric complexes with
      common-partner Smads (Co-Smads). The oligomeric Smad complexes then translocate
      into the nucleus, where they regulate the transcription of target genes by direct
      binding to DNA, interaction with various DNA-binding proteins, and recruitment of
      transcriptional coactivators or corepressors. A third class of Smads, inhibitory
      Smads (I-Smads), inhibits the signals from the serine/threonine kinase receptors.
      Since the expression of I-Smads is induced by the TGF-beta superfamily proteins,
      Smads constitute an autoinhibitory signaling pathway. The functions of Smads are
      regulated by other signaling pathways, such as the MAP kinase pathway. Moreover,
      Smads interact with and modulate the functions of various transcription factors
      which are downstream targets of other signaling pathways. Loss of function of
      certain Smads is involved in tumorigenesis, e.g., pancreatic and colorectal
      cancers. Analyses by gene targeting revealed pivotal roles of Smads in early
      embryogenesis, angiogenesis, and immune functions in vivo.

PMID- 10879284
TI  - MHC class II-restricted antigen processing and presentation.

PMID- 10879285
TI  - T-cell receptor crossreactivity and autoimmune disease.

PMID- 10879286
TI  - Strategies for immunotherapy of cancer.

PMID- 10879287
TI  - Tyrosine kinase activation in the decision between growth, differentiation, and
      death responses initiated from the B cell antigen receptor.
AB  - Immunoglobulin-containing receptors expressed on B lineage lymphocytes play
      critical roles in the development and function of the humoral arm of the immune
      system. The preB cell antigen receptor (preBCR) contains the immunoglobulin mu
      heavy chain (Ig mu) and signals to the preB cell that heavy chain rearrangement
      has been successful, a process termed heavy chain selection. The B cell antigen
      receptor (BCR) contains both Ig heavy and light chains and is expressed on
      immature and mature B cells before and after antigen encounter. Both receptor
      types from a complex with the Ig alpha and Ig beta proteins that link the
      predominantly extracellular Ig with intracellular signal transduction pathways.
      Signaling through the BCR induces different cellular responses depending on the
      nature of the signaling agent and the development stage of the target cell. These
      responses include clonal anergy and apoptotic deletion in immature B cells and
      survival, proliferation, and differentiation in mature B and preB cells. Several
      protein tyrosine kinases are activated rapidly following engagement of the
      BCR/preBCR complexes, including members of the Src family (Lyn and Blk), the
      Syk/ZAP70 family (Syk), and the Tec family (Btk). In this review, we discuss
      possible mechanisms by which engagement of these similar receptor complexes can
      give rise to different cellular responses and the role that these kinases play in
      this process.

PMID- 10879288
TI  - The 3' IgH regulatory region: a complex structure in a search for a function.

PMID- 10879289
TI  - [The roles for modeling in epidemiology].
AB  - Mathematical modelling in epidemiology was pioneered by D. Bernoulli in 1760 in
      his work demonstrating the effectiveness of the technique of variolation against
      smallpox. Mathematical epidemiology concerns presently infectious diseases (such
      as HIV infection, hepatitis C, Prion diseases, influenza, etc.) as well as non
      infectious diseases (e.g. cancer). The roles of modelling in epidemiology are: 1)
      description of complex data in order to facilitate the dissemination of results;
      2) demonstration of general laws governing the dynamics of epidemics; 3)
      estimation of the values of parameters that cannot be directly measured; 4)
      prediction of future disease burdens; 5) selection of optimal experimental
      designs.

PMID- 10879290
TI  - [Pollution and agricultural practices. 2 concepts: acceptable daily dose and
      chemo-defense].
AB  - Pollution coming from agricultural practices can exist: pesticides, veterinary
      drugs, heavy metals but also mycotoxins. However, these contaminants are always
      at low or trace doses in our environment (foods, water, air, soils). In terms of
      foods, two concepts have been developed to protect the consumers: acceptable
      daily intake (ADI) and maximum residue limits (MRL). The impact of this pollution
      on public health is not evident, in contradiction with the level of fear in the
      population. Moreover, the distinction made between natural and synthetic
      substances by the public in terms of toxicity is quite nonsense scientifically.
      Human beings and all living organisms have a good defence system against chemical
      xenobiotics which ensures their protection.

PMID- 10879291
TI  - [Organic synthesis].
AB  - Some comments on the problems that are encountered by organic chemists who
      attempt the total synthesis of a molecule having several asymmetric centers.
      These difficulties explain the relatively slow progress of that branch of
      chemistry, although some of its successes merit being considered works of art.

PMID- 10879292
TI  - A new case of trophobiosis between ants and Heteroptera.
AB  - Despite the large specific diversity of equatorial rainforests, Caternaultiella
      rugosa (Heteroptera; Plataspidae) was only noted on two euphorbiaceous trees
      (Bridelia micrantha and B. grandis) and was attended by two ant species,
      Camponotus brutus (Formicinae) and Myrmicaria opaciventris (Myrmicinae). We
      recorded semiochemical (attending workers palpated the dorsal abdominal glands of
      the nymphs) and semantic signals (nymphs ready to excrete honeydew raised their
      bodies; they alternated the extrusion and withdrawal of the first honeydew
      droplet when the workers did not immediately absorb the honeydew). Cat. rugosa
      was recorded in carton pavilions built by the ants at the base of the tree
      trunks. During proliferations of the population, clusters of nymphs and adults
      developed outside pavilions. In the latter case, M. opaciventris workers did not
      modify their rhythm of activity in order to attend these clusters, while Camp.
      brutus workers, normally nocturnal, attended them day and night.

PMID- 10879293
TI  - [Metaplasia of aortic tissue into tracheal tissue. Surgical perspectives].
AB  - Tracheal reconstruction after extensive resection remains an unsolved surgical
      problem. Numerous attempts have been made using tracheal grafts or prosthetic
      conduits with disappointing results. In this study, we propose a new alternative
      using an aortic autograft as tracheal substitute. In a first series of
      experiments, a half circumference of two rings was replaced with an autologous
      carotid artery patch. In a second series, a complete segment of trachea was
      replaced with an autologous aortic graft supported by an endoluminal tracheal
      stent. No dehiscence or stenosis was observed. Microscopic examinations at 3 and
      6 months showed the replacement of the aortic tissue by tracheal tissue
      comprising neoformation of cartilage and mucociliary or non-keratinizing
      metaplastic polystratified squamous epithelium. Although these results need to be
      confirmed by a larger series of experiments, they showed that a vascular tissue
      placed in a different environment with a different function can be submitted to a
      metaplastic transformation which tends to restore a normal structure adapted to
      its new function. These remarkable findings offer new perspectives in tracheal
      reconstruction in human.

PMID- 10879294
TI  - Further evidence of the existence of oviparous populations of Lacerta (Zootoca)
      vivipara in the NW of the Balkan Peninsula.
AB  - The lizard Lacerta (Zootoca) vivipara, which is viviparous in the greatest part
      of its distribution range, has however some oviparous populations on the southern
      margin of its range. The present study aimed at determining the reproductive mode
      and the ATA (aspartate transaminase) enzyme characteristics of four populations
      in Slovenia and one population in Croatia. The Slovenian females studied here
      presented an oviparous reproductive mode which strongly resembled those observed
      in the oviparous populations of south-western France and north-western Spain. Our
      electrophoresis analyses revealed the existence of two distinct alleles, ATA-150
      and ATA-200, in the oviparous populations of Slovenia. These alleles were
      identical to those observed in the French and Spanish oviparous group and were
      distinct from the allele ATA-100 characterizing the viviparous populations that
      we had previously studied. Although we did not study the reproductive mode of
      Croatian females, the allele ATA-200 observed in one population of Croatia
      strongly suggested that this population might also be oviparous.

PMID- 10879295
TI  - [Did the Erve Valley in Mayenne (the Armoricain Massif, France) play the role of
      a refuge station during the last (Weichselien) glaciation?].
AB  - Palynological analysis of the basal sedimentary sequence of a peat bog in the
      upper northeastern part of Mayenne (Massif Armoricain, France) revealed the
      existence of two temperate oscillations towards the end of the Weichselian
      glaciation, which were related chronologically by AMS C14 dating to the Kesselt
      and Tursac interstadials already reported at cave sites. Pollen diagrams recorded
      mesothermophilic arboreal taxa apparently disseminated from a refuge station
      possibly corresponding to the Erve valley.

PMID- 10879296
TI  - Are the Mediterranean ascoglossan molluscs Oxynoe olivacea and Lobiger
      serradifalci suitable agents for a biological control against the invading
      tropical alga Caulerpa taxifolia?
AB  - The Mediterranean ascoglossan Oxynoe olivacea and Lobiger serradifalci, which are
      scarce in meadows of their usual food the alga Caulerpa prolifera, have become
      adapted to feeding on the invading tropical alga Caulerpa taxifolia. Grazing
      rates are low (O. olivacea destroys only a 5-cm C. taxifolia frond in 3-7 d). The
      grazing rates are a function of temperature. Despite a high spawning frequency
      (0.25 egg-mass.day-1) and a large number of eggs released per spawning event (O.
      olivacea: from 2,545 to 29,128 eggs.spawning-1; L. serradifalci: from 12,112 to
      48,448 eggs.spawning-1), the recruitment on Caulerpa meadows is usually low due
      to the hazardous pelagic development of the larvae. The possible use of these
      molluscs as agents of biological control against C. taxifolia appears to be
      possible only through an artificial enhancement of their populations after
      cultivation of the veligers and release of juveniles during the winter season.
      This means of control is discussed and compared with the possible use of tropical
      ascoglossan species.

PMID- 10879297
TI  - [Utilization of a biogeochemical model in dendroecology. Application to the
      Cembro pine].
AB  - Dendroecology, which is based on annual growth variable measurements, is in
      possession of data particularly well adapted to analyse the impact of global
      change on vegetation production. But the classical statistical methods of
      quantification of tree ring-climate relationship cannot take into account the
      effect of CO2 increase. Therefore, a biogeochemistry model (BIOME3) has been
      adapted to these data and then validated on Pinus cembra. The results indicate
      that the production is reduced by 14% if only the climatic changes are taken into
      account. If both climatic changes and CO2 increase are taken into account the
      production is increased by 62%. The direct fertilisation effect of CO2 increase
      will have more influence on the productivity than the indirect climatic effect.

PMID- 10879298
TI  - Evidence from polychromatism and bioluminescence that the cosmopolitan ophiuroid
      Amphipholis squamata might not represent a unique taxon.
AB  - Individuals of the cosmopolitan ophiuroid Amphipholis squamata were collected
      from eight stations. Eleven colour varieties were described and their
      distribution was non-random among stations. This suggests that the varieties
      differ in ecophysiologic tolerance and that their geographical distribution is
      modulated by environmental conditions. Varieties also differed in
      bioluminescence. Contrary to kinetics, intensity of light production varied among
      co-occurring varieties, meaning that they have similar bioluminescent reactions
      but a different amount of bioluminescent reagent. Light intensity differed in
      absolute value among stations but the rank position of each variety relative to
      others remained constant from one station to another. The 'colour
      bioluminescence' link appeared clearly fixed (the same level of bioluminescence
      for the same variety) and is suggested to be of genetic origin. The species 'A.
      squamata' may then be a mosaic of genetically different entities (the varieties)
      rather than a unique cosmopolitan taxonomic entity.

PMID- 10879299
TI  - John T. McCarthy, M.D. 1929-2000: a life well lived.

PMID- 10879300
TI  - Photo quiz. Xanthoma disseminatum.

PMID- 10879301
TI  - Fusarium fingernail infection responsive to fluconazole intermittent therapy.
AB  - A case of fingernail infection by Fusarium is presented. This nondermatophytic
      mold is an infrequent cause of onychomycosis, more typically involving the great
      toenail. Characteristic histologic features including the presence of hyphae and
      chlamydoconia are helpful in rapid diagnosis and selection of appropriate
      antifungal therapy. Although Fusarium has shown resistance to most antifungal
      medications in vitro, intermittent therapy with fluconazole led to improvement in
      this patient.

PMID- 10879302
TI  - Chickenpox.

PMID- 10879303
TI  - Localized whirlpool folliculitis in a football player.
AB  - Pseudomonas aeruginosa folliculitis occurs in patients exposed to contaminated
      water. Most out-breaks are associated with whirlpools. The infection is
      characterized by follicular, erythematous papules and pustules located on
      immersed body surfaces. Most reported cases are the result of recreational water
      use, occur in a diffuse pattern, and are devoid of green pustular pigment
      changes. The case described occurred in a football player after whirlpool
      treatment for an ankle strain. Green pustules and a localized affected area are
      unusual aspects of this case.

PMID- 10879304
TI  - Recalcitrant molluscum contagiosum in an HIV-afflicted male treated successfully
      with topical imiquimod.
AB  - Molluscum contagiosum is a common cutaneous infection complicating the course of
      patients afflicted with acquired immunodeficiency syndrome. We describe a human
      immunodeficiency virus-positive patient with a disfiguring molluscum contagiosum
      infection of the face. Conventional cytodestructive therapies failed in this
      patient, but imiquimod 5% cream, an immunomodulator, clinically cleared his
      cutaneous disease.

PMID- 10879305
TI  - Myelodysplastic syndrome presenting as cutaneous purpura.
AB  - Myelodysplastic syndrome is a preleukemic, clonal disorder of the hematopoetic
      stem cell. Cutaneous manifestations include infections, vasculitis, neutrophilic
      dermatoses, and leukemia cutis. Senile purpura is a common condition occurring in
      elderly individuals who lack other systemic or hematologic diseases. We present a
      case of myelodysplastic syndrome in which cutaneous lesions resembling senile
      purpura were the initial clinical manifestation.

PMID- 10879306
TI  - Interactive medicine: resources in dermatology and dermatologic surgery.
AB  - The Internet has proved to be a useful resource in various fields of medicine.
      Within the field of Dermatology, Internet sites appeal to specialists in
      dermatology, non-specialist physicians, medical students, and the lay public. In
      the past 2 years, United States physicians' regular Internet use has increased
      300%, according to an ongoing study conducted by the Santa Clara-based Healtheon
      Corporation. The phenomenon of increased Internet usage is explainable. Patients
      have access to the Internet and often consult net sources before they see their
      physician; therefore, it is very important that physicians are likewise
      "connected" to enhance patient communication. Careful study of approximately 300
      Internet sites has yielded a reader-friendly presentation of only the sites that
      should be most useful to practitioners, medical students, and the lay public. The
      objective is to promote public health through doctor-patient communication and
      through the use of valuable interactive medical resources.

PMID- 10879307
TI  - Neonatal lupus erythematosus.
AB  - Neonatal lupus erythematosus (NLE) is a rare disease characterized by the
      transplacental passage from the mother to the fetus of autoantibodies, in
      particular anti-Ro(SS-A), anti-La(SS-B), or both. The majority of infants with
      NLE exhibit isolated congenital heart block, cutaneous lesions analogous to those
      of adult subacute cutaneous lupus erythematosus, or both. We report a case of NLE
      in a 3-month-old male infant, born to a clinically asymptomatic mother,
      presenting small, annular, erythematous plaques with sharp, hyperkeratotic
      borders and central clearing localized at the eyebrow region. Both the infant and
      the mother were positive for anti-Ro(SS-A).

PMID- 10879308
TI  - Ulcus vulvae acutum.
AB  - An acute vulvar ulcer was diagnosed based on a case history of a 17-year-old girl
      with genital ulcers. No relevant causative factors could be established. The
      gangrenous form of the disease, cutaneous anergy, and the cultured anaerobic
      pathogens suggested the possibility of an infectious pathogenesis.

PMID- 10879309
TI  - Clindamycin-induced acute generalized exanthematous pustulosis.
AB  - Acute generalized exanthematous pustulosis is a rare but distinctive entity that
      may be associated with various etiologies. Drug exposure is the most common
      cause. We present the first report of acute generalized exanthematous pustulosis
      induced by the drug clindamycin.

PMID- 10879310
TI  - Bowen's disease of the glans penis (erythroplasia of Queyrat) in plasma cell
      balanitis.
AB  - We report a case of a persistent penile plaque on the glans penis of allegedly
      more than 20 years' duration, which was refractory to circumcision and local
      treatment. Over the years, the patient repeatedly presented with a circumscribed
      inflammatory lesion of the glans penis, diagnosed as Zoon's balanitis on the
      basis of clinical aspects and two biopsies. Because of unresponsiveness of the
      lesion to circumcision and focal steroid infiltration, repeated biopsies were
      performed in an attempt to rule out malignancy. Two further biopsies were carried
      out. One again showed the features of a plasmacellular inflammation, while the
      other finally revealed the histopathologic features of erythroplasia of Queyrat
      (carcinoma in situ or Bowen's disease of the glans penis). We assume that either
      the former biopsy specimens were taken from a plasma cell-rich reactive
      infiltrate around the neoplastic lesion, or that carcinoma in situ may have
      arisen due to the chronic inflammation of Zoon's balanitis plasmacellularis.
      Radiotherapy was performed with good clinical response and subsequent
      histopathologic proof of complete remission of the lesion.

PMID- 10879311
TI  - A newly formulated topical triple-antibiotic ointment minimizes scarring.
AB  - A randomized study of polymyxin B sulfate-bacitracin zinc-neomycin sulfate versus
      simple gauze-type dressings in dermabrasion wounds assessed the effects that each
      treatment had on scarring. Each of three uniform dermabrasion wounds created on
      the upper backs of 70 subjects was treated concurrently with a triple-antibiotic
      ointment (polymyxin B-bacitracin-neomycin), a double antibiotic (polymyxin B
      bacitracin), or a simple, non-occlusive, gauze-type dressing, twice daily for up
      to 14 days. Pigmentary changes and textural changes (scarring) appearing after
      healing at the skin surface test sites were compared to adjacent normal skin at
      45 and 90 days post-dermabrasion. These changes were graded visually utilizing
      fluorescent light, long-wave ultraviolet light, and by clinical color
      photography. The triple-antibiotic ointment was superior to simple gauze-type
      dressing alone in minimizing the scarring observed in dermabrasion wounds. The
      benefit of this new ointment was more pronounced in its effect on pigmentary
      changes.

PMID- 10879312
TI  - How do OB delivery volume and training adequacy correlate?

PMID- 10879313
TI  - Practical idealism: a blueprint for caring.

PMID- 10879314
TI  - Do literature and the arts make us better doctors?

PMID- 10879315
TI  - Residency program vision.

PMID- 10879316
TI  - The physician as ethics educator.

PMID- 10879317
TI  - What kind of research in family medicine--further reflections. 1980.

PMID- 10879318
TI  - Mirror, mirror on the wall.

PMID- 10879319
TI  - Sentinel practices. 1982.

PMID- 10879320
TI  - Putting practice into research: a 20-year perspective.

PMID- 10879321
TI  - A literature analysis in family medicine and general practice. 1981.

PMID- 10879322
TI  - Anything different?

PMID- 10879323
TI  - An introduction to the National Institutes of Health. 1984.

PMID- 10879324
TI  - Research: traveling the yellow brick road.

PMID- 10879325
TI  - Conference formats in family practice residencies.
AB  - BACKGROUND: This study was intended to establish national baseline data of the
      current structure of conferences at family practice residencies and to determine
      if there are differences in conference formats among types of residencies.
      METHODS: An author-developed survey was mailed to 331 programs stratified by type
      and randomly selected. Statistical analysis included chi-square tests and non
      parametric tests. RESULTS: The response rate was 84%. The average time devoted to
      lectures was 4.5 hours a week, with the noon hour the most common time. Most
      speakers were from within the program, and community-based family physicians were
      rarely present. Structural changes were frequent. CONCLUSIONS: Results indicate
      that a variety of formats are implemented for meeting Residency Review Committee
      requirements in the structure of family practice residencies' conferences.
      Program settings do influence how conferences are structured. More research is
      needed on this neglected area of formal resident education.

PMID- 10879326
TI  - "Thou dost protest too much": lessons from the last ASPN convocation.

PMID- 10879327
TI  - Are recent cohorts healthier than their predecessors?
AB  - OBJECTIVES: This article examines changes in the health status of Canadian adults
      between 1978/79 and 1996/97. DATA SOURCES: Data are from the the Canadian Vital
      Statistics Data Base, the 1991 General Social Survey, the 1978/79 Canada Health
      Survey (CHS), and the 1996/97 National Population Health Survey (NPHS).
      ANALYTICAL TECHNIQUES: Age-specific mortality rates are presented for 1978 and
      1996. The cumulative incidence of heart disease is shown for 1991. Cross
      sectional comparisons of prevalence rates for selected chronic conditions,
      activity limitation, disability days, smoking and overweight are shown for
      1978/79 and 1996/97. Multiple logistic regression models were used to test
      differences in odds ratios for the chronic conditions and for activity limitation
      between the CHS and the NPHS. SUDAAN, which accounts for the complex survey
      design, was used to estimate standard errors of the prevalence and of the
      coefficients in the logistic model. MAIN RESULTS: Lower mortality rates and lower
      prevalence of heart disease, high blood pressure, arthritis and activity
      limitation suggest that recent cohorts are healthier than previous cohorts. When
      the age effect was controlled along with education and income, the odds of having
      these conditions were generally lower for each successive cohort, and lower in
      the mid-1990s than in the late 1970s. However, the odds of having diabetes were
      higher in 1996/97 than in 1978/79, and higher among more recent cohorts than
      among earlier cohorts.

PMID- 10879328
TI  - Oral contraceptive use.
AB  - OBJECTIVES: This article profiles Canadian women aged 15 to 49 who use oral
      contraceptives (OCs), and compares certain of their characteristics with those of
      non-users. It also examines associations between OC use and selected
      characteristics, including cardiovascular risk factors. DATA SOURCE: The data are
      from the cross-sectional household component of Statistics Canada's 1996/97
      National Population Health Survey. The analysis is based on a sample of 21,996
      women aged 15 to 49, weighted to represent an estimated 7.6 million women.
      ANALYTICAL TECHNIQUES: Cross-tabulations were used to estimate the percentage of
      women aged 15 to 49 who use OCs and to compare selected health behaviours of
      users and non-users. A multiple logistic regression model was used to model
      relationships between selected characteristics and OC use. MAIN RESULTS: An
      estimated 1.3 million women aged 15 to 49, or 18%, reported using OCs in 1996/97.
      OC use was significantly associated with being young, unmarried, sexually active,
      and having prescription drug insurance and relatively high education. About one
      third of OC users also smoked.

PMID- 10879329
TI  - Changes in social support in relation to seniors' use of home care.
AB  - OBJECTIVES: This article examines seniors' entry into government-supported home
      care in relation to changes in levels of social support and in living
      arrangements. DATA SOURCE: The analysis is based on longitudinal data from the
      household component of the first two cycles of the National Population Health
      Survey, conducted by Statistics Canada in 1994/95 and 1996/97. Data from a sample
      of 2,044 people aged 65 or older who were followed prospectively were weighted to
      represent 2.7 million household-dwelling seniors. ANALYTICAL TECHNIQUES:
      Descriptive data were produced using bivariate frequencies. A multiple logistic
      regression model was used to examine associations between home care entry and
      changes in levels of social support and in living arrangements, while controlling
      for demographic and health-related factors. MAIN RESULTS: Among people aged 65 or
      older who did not receive government-supported home care in 1994/95, an estimated
      7% (192,000) were receiving these services in 1996/97. Changes in social support
      and in living arrangements between 1994/95 and 1996/97 were significantly
      associated with home care entry.

PMID- 10879330
TI  - Living at home or in an institution: what makes the difference for seniors?
AB  - OBJECTIVES: This article examines some of the health and socio-demographic
      factors associated with living in long-term health care facilities rather than in
      private households, for elderly people with various levels of disability. DATA
      SOURCE: The data are from the 1996/97 National Population Health Survey conducted
      by Statistics Canada. Data from a sample of 1,711 people aged 65 or older living
      in long-term health care facilities and 13,363 in private households were
      weighted to represent about 185,100 and 3.4 million seniors, respectively.
      ANALYTICAL TECHNIQUES: Descriptive data were produced using bivariate
      frequencies. Multiple logistic regression models were used to examine
      associations between living in long-term health care facilities and selected
      health and socio-demographic characteristics for seniors with self-reported
      severe, moderate or no disability. MAIN RESULTS: While health status was strongly
      associated with residence in a long-term health care facility, the absence of a
      spouse, low income, low education, and advanced age were also significant.

PMID- 10879331
TI  - Long-term follow-up of premature infants treated with prophylactic, intratracheal
      recombinant human CuZn superoxide dismutase.
AB  - OBJECTIVE: To examine the long-term effects of treatment with recombinant human
      CuZn superoxide dismutase (rhSOD) in infants enrolled previously in two placebo
      controlled trials. STUDY DESIGN: Records for 46 (88%) infants were examined, with
      19 infants having received either single or multiple intratracheal (i.t.) doses
      of placebo, 12 having received a single i.t. dose of rhSOD, and 15 having
      received multiple i.t. doses of rhSOD. Mean age at follow-up was 28 months
      corrected age. Records were examined for neurologic dysfunction, developmental
      delay, and any significant medical disorders. RESULTS: Four placebo infants (21%)
      had evidence of neurodevelopmental abnormalities and four infants developed
      asthma. Four single-dose rhSOD infants (33%) had neurodevelopmental abnormalities
      and two infants developed asthma. One multiple-dose rhSOD infant had evidence of
      neurodevelopmental abnormalities and one developed asthma. No other differences
      were found between the placebo and rhSOD groups. CONCLUSION: Preliminary data
      suggest that rhSOD is safe and not associated with any long-term adverse effects.
      Further results will depend on the results of multicenter trials of rhSOD in
      preterm infants.

PMID- 10879332
TI  - Effects of intrapartum administration of invert sugar and D5LR on neonatal blood
      glucose levels.
AB  - OBJECTIVE: To compare the effects of D5LR and invert sugar administered
      intrapartum on neonatal blood glucose concentrations. STUDY DESIGN: This is a
      prospective, randomized, double-blind study. A total of 32 insulin-requiring
      diabetic patients were randomized to receive either intravenous 10% invert sugar
      or lactated Ringer's solution with 5% dextrose (D5LR). Regular insulin was given
      intravenously with an infusion pump to maintain the plasma glucose concentration
      between 60 and 90 mg/dl. Neonatal blood glucoses were measured at 30 minutes
      after birth, four times every hour, and thereafter as indicated. Student's t-test
      was used for continuous variables and Fisher's exact test was used for
      categorical data. RESULTS: There were no differences in neonatal blood glucose
      levels, incidence of neonatal hypoglycemia, or length of neonatal hospital stay
      between the two groups. CONCLUSION: Intrapartum administration of invert sugar is
      not associated with better neonatal homeostasis of glucose compared with using
      D5LR. Thus, given the expense of invert sugar, D5LR appears to be preferable for
      intrapartum control of maternal blood glucose.

PMID- 10879333
TI  - The effect of integrating substance abuse treatment with prenatal care on birth
      outcome.
AB  - OBJECTIVE: To determine whether engaging pregnant substance abusers in an
      integrated program of prenatal care and substance abuse treatment would improve
      neonatal outcomes. STUDY DESIGN: The subjects were women who voluntarily enrolled
      in Project Link, an intensive outpatient substance abuse treatment program at
      Women and Infants Hospital, Providence, RI. A total of 87 women received
      substance abuse treatment in conjunction with their prenatal care; the comparison
      group of 87 women received equivalent prenatal care but did not enroll in the
      substance abuse treatment program until after they delivered. The two groups of
      women were similar demographically and socioeconomically and had similar
      substance abuse histories. Univariate and multivariate analyses were performed.
      The key outcomes were gestational age at delivery, birth weight, preterm
      delivery, Apgar scores, and neonatal intensive care admission rate. Factors
      controlled in the multivariate models included demographics, socioeconomic
      status, parity, and prenatal care. RESULTS: Infants born to women who enrolled
      prenatally were 400 gm heavier (p < 0.001), and their gestational age was 2 weeks
      longer (p < 0.001) than infants of mothers enrolled postpartum. In addition, they
      were approximately one-third as likely to be born with a low birth weight (p <
      0.01) and approximately one-half as likely to be admitted to the neonatal
      intensive care unit (p < 0.05). CONCLUSION: Neonatal outcome is significantly
      improved for infants born to substance abusers who receive substance abuse
      treatment concurrent with prenatal care compared with infants born to substance
      abusers who enter treatment postpartum.

PMID- 10879334
TI  - Cytokines enhance opsonophagocytosis of type III group B Streptococcus.
AB  - Neutrophil (polymorphonuclear leukocyte (PMN)-mediated killing is important to
      host defense against type III group B Streptococcus (GBS). In neonates, a
      qualitative and quantitative deficiency in PMN-mediated host defense may
      contribute to an impaired neonatal response to this pathogen. OBJECTIVE: The
      purpose of this study was to determine whether tumor necrosis factor-alpha (TNF
      alpha), granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage
      colony-stimulating factor (GM-CSF) would enhance neonatal PMN-mediated killing of
      III GBS. STUDY DESIGN: PMNs from adults or neonates were incubated with TNF
      alpha, G-CSF, or GM-CSF; next, PMN-mediated killing of III GBS was assessed in an
      in vitro opsonophagocytic assay. RESULTS: Treatment of PMNs with these cytokines
      for an interval of 5 minutes before addition of GBS to the reaction mixture
      enhanced opsonophagocytosis of bacteria both by adult PMNs and neonatal PMNs. The
      effect was statistically significant for TNF-alpha- and GM-CSF-treated adult PMNs
      and for GM-CSF-treated neonatal PMNs. The enhanced killing of III GBS by GM-CSF
      treated PMNs was reduced by monoclonal antibody blockade of FcRIII. CONCLUSION: G
      CSF enhances the neonatal PMN-mediated killing of III GBS in vitro. These studies
      suggest that use of FcRIII receptors may be one mechanism by which GM-CSF
      augments the PMN-mediated killing of III GBS. The addition of purified
      immunoglobulin G containing III GBS-specific antibody facilitated
      opsonophagocytosis by GM-CSF-treated PMNs. We speculate that the administration
      of GM-CSF alone or in combination with intravenous immunoglobulin may improve the
      neonatal host response to III GBS.

PMID- 10879335
TI  - Optimal gestational age for twin delivery.
AB  - OBJECTIVE: We evaluated the timing of twin delivery associated with perinatal
      outcome in gestations of at least 36 completed weeks. STUDY DESIGN: This was a
      retrospective analysis of infant and maternal hospital records for a consecutive
      series of twin deliveries at New York Hospital-Cornell Medical Center. The
      inclusion criteria were delivery after 36 weeks' gestation during a 7-year period
      (1987 to 1993), without congenital anomalies or early fetal demise. Adverse
      perinatal outcomes were compared between deliveries before 38 weeks' gestational
      age and those at or after 38 weeks' gestation. RESULTS: Of 776 twin deliveries
      during the study period, 329 met the inclusion criteria. Adverse perinatal
      outcome was significantly higher among the twin pregnancies that delivered before
      38 weeks' gestation compared with those that delivered at or after 38 weeks'
      gestation. Twin pregnancies that delivered between 36 and 37 weeks' gestation
      were 13 times more likely to require neonatal intensive care compared with those
      who delivered at or after 38 weeks' gestation (95% confidence interval 1.8 to
      95.9; p < 0.001). CONCLUSION: In uncomplicated twin gestations, delivery at
      between 36 and 37 weeks' gestation was not associated with a reduction in
      neonatal complications compared with deliveries at or after 38 weeks' gestation.

PMID- 10879336
TI  - Gastroesophageal reflux in very low birth weight infants: association with
      chronic lung disease and outcomes through 1 year of age.
AB  - OBJECTIVE: To analyze the association between chronic lung disease (CLD) and
      clinically diagnosed gastroesophageal reflux (GER) in very low birth weight
      (VLBW) infants, and between GER and outcomes at 1 year adjusted age. METHODS: A
      total of 375 consecutively born VLBW infants with CLD and 345 gestational age
      matched controls were studied. Records were reviewed to ascertain which infants
      were diagnosed with GER (based on clinical suspicion or confirmatory tests) and
      which infants had delayed growth or development at 1 year adjusted age. RESULTS:
      Infants with CLD were treated for GER more frequently than controls (CLD: 27%
      versus controls: 9%; p < 0.0001). Among infants with CLD, those with and without
      GER were comparable in terms of the days on supplemental oxygen [124 (64 to 93)
      vs 121 (47 to 394)] and the proportion with cystic changes on chest radiograph
      (44% vs 47%). Comparing outcomes at 1 year for infants with and without GER, no
      differences were found in the rates of Bayley Mental Developmental and
      Psychomotor Developmental Indices of < 70, cerebral palsy, and measurements below
      the 10th percentile. CONCLUSION: Among VLBW infants, an association exists
      between CLD and GER, although this association might be due to greater diagnostic
      suspicion in infants with CLD. In VLBW infants, GER does not appear to increase
      the risk of delayed growth or development.

PMID- 10879337
TI  - Cerebral blood flow velocity changes after bovine natural surfactant
      instillation.
AB  - OBJECTIVE: To determine the effects of bovine natural surfactant (beractant)
      instillation on cerebral hemodynamics in preterm infants with respiratory
      distress syndrome (RDS). STUDY DESIGN: Preterm infants who required surfactant
      for RDS were enrolled. Cerebral blood flow velocity (CBFV) waveforms from the
      pericallosal artery were analyzed by pulsed Doppler ultrasonography with the
      anterior fontanel serving as an acoustic window. CBFV was measured before and at
      5, 10, 20, and 30 minutes after the first dose of a bolus instillation of
      surfactant in four aliquots. Simultaneously with CBFV measurements, mean blood
      pressure (MBP), heart rate, and ventilator settings were recorded. pH, PACO2, and
      PAO2 before and at 30 minutes after surfactant administration were also
      determined. RESULTS: The 30 enrolled preterm infants had a mean birth weight of
      973 gm (513 to 1996 gm) and a mean gestational age of 27 weeks (23 to 33 weeks).
      Mean postnatal age at surfactant administration was 4.7 +/- 2.7 hours. There were
      no significant changes in pH and PACO2 before and at 30 minutes after surfactant
      (before surfactant: mean pH of 7.29 +/- 0.07 and mean PACO2 of 44.4 +/- 7.1 torr;
      after surfactant: mean pH of 7.31 +/- 0.07 and mean PACO2 of 42.7 +/- 8.3 torr).
      PAO2 increased significantly from a pre-surfactant mean of 83 torr to 130 torr at
      30 minutes after surfactant (p < 0.05), with no significant changes in mean
      airway pressure. There were no significant changes in MBP, heart rate, mean CBFV,
      peak systolic flow velocity, and diastolic flow velocity before and after
      surfactant instillation regardless of gestational age. Individual changes in mean
      CBFV were related to MBP changes (p < 0.001, linear mixed models with random
      effects). CONCLUSION: In low birth weight infants with RDS, bovine surfactant
      instillation is not associated with a significant alteration in cerebral
      hemodynamics. However, the direct relationship between CBFV and MBP is consistent
      with the reported pressure-passive cerebral circulation in sick preterm infants.

PMID- 10879338
TI  - Professional liability in a neonatal intensive care unit: a review of 20 years'
      experience.
AB  - OBJECTIVE: To examine neonatal intensive care unit (NICU) malpractice claims and
      identify common characteristics likely to result in malpractice. STUDY DESIGN: A
      retrospective study (1972 to 1992) at a tertiary care children's hospital
      examining malpractice claims involving NICU infants. RESULTS: A total of 31 cases
      of malpractice out of 9367 NICU admissions (incidence 0.33%) were found. Although
      not statistically significant, the incidence of legal action increased with NICU
      growth from 0.19% (1972 to 1974) to 0.39% (1980 to 1992). Infants who were
      significantly over-represented in malpractice cases compared with the general
      NICU population included those who were full-term, white, privately insured, and
      those with neurologic conditions. Families' motives for legal action included (1)
      treatment error/delay (48%), (2) missed/delayed diagnosis (16%), (3) equipment
      malfunction/misuse (6%), and (4) general improper care (30%). CONCLUSION: Based
      on this research, three factors may be associated with increased risk of
      malpractice in the NICU: (1) increased unit growth, (2) parental perceptions of
      negligence, and (3) full-term infants with diagnoses associated with neurologic
      conditions.

PMID- 10879339
TI  - Pumps for peanuts: leveling the field in the neonatal intensive care unit.

PMID- 10879340
TI  - Ending innovative therapy for infants at the margins of viability: case of twins
      H.

PMID- 10879341
TI  - Risk of meconium-stained amniotic fluid in different ethnic groups.
AB  - BACKGROUND: Recent studies indicate that the risk of meconium-stained amniotic
      fluid (MSAF) varies in different ethnic groups. This study prospectively examined
      the ethnic variation of MSAF and meconium aspiration syndrome, adjusting for
      gravidity, gestational age (GA), and birth weight. METHOD: The study population
      consisted of 6901 consecutive live births and included 31 different
      nationalities, seven main ethnic (race) groups, gravidity between 1 and 19, GA
      between 22 and 44 weeks, and birth weights between 350 and 6292 gm. RESULTS: The
      overall incidence of MSAF was 19% (13% thin, 6% thick). The prevalence of
      meconium aspiration syndrome was 5% in thick MSAF and none in thin MSAF. The
      incidence of MSAF differs significantly by ethnicity (14% to 30%), gravidity (17%
      to 23%), GA (6% to 46%), and birth weight (11% to 28%). Multivariate logistic
      regression analysis using the same variable showed that being black African, post
      term, with a gravidity of > or = 7 and a birth weight of > or = 4000 gm
      significantly increased the chance for MSAF but not meconium aspiration syndrome.
      After controlling for these clinical variables, the black African infants had a
      higher percentage of MSAF at all GAs compared with the other ethnic groups.
      CONCLUSION: This study showed that the risk of MSAF varied by ethnicity and
      increased with higher gravidity, a GA of > 42 weeks, and a birth weight of > or =
      4000 gm The higher incidence of MSAF without an increase in meconium aspiration
      syndrome in some ethnic groups may indicate advancing maturity of the
      gastrointestinal system in black ethnic groups compared with others of the same
      GA.

PMID- 10879342
TI  - Secondary infection presenting as recurrent pulmonary hypertension.
AB  - Primary infection in the neonate, especially group B streptococcal infection, has
      long been recognized as a cause of persistent pulmonary hypertension of the
      newborn (PPHN), sometimes requiring treatment with inhaled nitric oxide (iNO) and
      extracorporeal membrane oxygenation (ECMO). However, secondary nosocomial
      infections in the neonatal period have not been widely reported as a cause of
      severe recurrent pulmonary hypertension (PHTN). We now present two cases of
      secondary infection in the neonate leading to significant PHTN. In both cases,
      the infants presented with PPHN soon after birth, requiring transfer to a level 3
      neonatal intensive care unit and treatment with high-frequency oscillatory
      ventilation and iNO. After successful resolution of the initial PPHN, including
      extubation to nasal cannula, both infants developed signs of severe recurrent
      PHTN, leading to reintubation, high-frequency oscillatory ventilation and iNO
      therapy, and consideration of ECMO. In both cases, blood cultures taken at the
      time of recurrence of PHTN returned positive, one for Staphylococcus epidermidis,
      the other for methicillin-resistant Staphylococcus aureus. These unusual cases
      present the possibility of severe recurrent PHTN requiring iNO or ECMO in the
      setting of secondary infection. We speculate that these infants, although
      extubated after their first episodes of PHTN, were at risk for recurrence of PHTN
      due to continued pulmonary vascular reactivity.

PMID- 10879343
TI  - Citrobacter sepsis and severe newborn respiratory failure supported with
      extracorporeal membrane oxygenation.
AB  - An infant with fulminant Citrobacter sepsis and respiratory failure is presented.
      The severity of respiratory failure and the need for systemic heparinization on
      extracorporeal membrane oxygenation delayed the opportunity of initial lumbar
      puncture to rule out meningitis. The infant was successfully treated with
      extracorporeal membrane oxygenation and long-term antibiotics. Repeated cranial
      computed tomography scans remained negative for intracerebral abscesses, and the
      infant is within normal limits for growth, neurologic status, and developmental
      status.

PMID- 10879344
TI  - Collodion baby: a case report.
AB  - A case report of a collodion baby born in a community hospital who was diagnosed,
      stabilized, and transferred for dermatologic management is presented.
      Differential diagnosis based on cornification disorder phenotypes is outlined.
      The initial stabilization, management, and nursing considerations of the infant
      with impaired barrier function of the skin are outlined.

PMID- 10879345
TI  - Fetal heart rate monitoring casebook. Airbag-associated rupture of membranes:
      evaluation of trauma in pregnancy.

PMID- 10879346
TI  - Special imaging casebook. Hydranencephaly.

PMID- 10879347
TI  - Comments regarding "Impact of infants born at the threshold of viability on the
      neonatal mortality rate in Colorado".

PMID- 10879348
TI  - Intraoperative fetal monitoring during nonobstetric surgery.

PMID- 10879349
TI  - Anesthesia for cesarean section and newborn jaundice.

PMID- 10879350
TI  - Making Rorschach interpretation as good as it can be.
AB  - This article delineates six guidelines for enhancing the quality and utility of
      interpretations derived from the Rorschach inkblot method. These include (a)
      using all of the available structural, thematic, and behavioral data in arriving
      at interpretations; (b) focusing interpretive statements primarily on personality
      processes and drawing clinical conclusions and recommendations secondarily on the
      basis of identified personality processes; (c) addressing interpretations to both
      personality strengths and personality weaknesses to attend equally to adaptive
      capacities and maladaptive tendencies; (d) formulating and conveying
      interpretations at appropriate levels of certainty to distinguish clearly between
      probable fact and possible conjecture; (e) pursuing and expressing both
      nomothetic and idiographic implications of interpretations to the fullest
      possible extent, recognizing that personality is best described by considering
      both how people resemble and how they differ from each other; and (f) grounding
      the implications of interpretations in each respondent's cultural context to take
      adequate account of the mediation of cultural relativism between personality
      characteristics and their adaptive consequences.

PMID- 10879351
TI  - A replication of Rorschach and MMPI-2 convergent validity.
AB  - We replicated prior research on Rorschach and MMPI-2 convergent validity by
      testing 8 hypotheses in a new sample of patients. We also extended prior research
      by developing criteria to include more patients and by applying the same
      procedures to 2 self-report tests: the MMPI-2 and the MCMI-II. Results supported
      our hypotheses and paralleled the prior findings. Furthermore, 3 different tests
      for methodological artifacts could not account for the results. Thus, the
      convergence of Rorschach and MMPI-2 constructs seems to be partially a function
      of how patients interact with the tests. When patients approach each test with a
      similar style, conceptually aligned constructs tend to correlate. Although this
      result is less robust, when patients approach each test in an opposing manner,
      conceptually aligned constructs tend to be negatively correlated. When test
      interaction styles are ignored, MMPI-2 and Rorschach constructs tend to be
      uncorrelated, unless a sample just happens to possess a correlation between
      Rorschach and MMPI-2 stylistic variables. Remaining ambiguities and suggestions
      for further advances are discussed.

PMID- 10879352
TI  - Effects of acculturation on the MMPI-2 scores of Asian American students.
AB  - The use of the MMPI-2 (Butcher, Dahlstron, Graham, Tellegen, & Kaemmer, 1989)
      with minorities has been questioned due to potential misinterpretations related
      to cultural differences. This study examined acculturative differences among
      Asian American college students and their scores on the validity and clinical
      scales. A sample of Asian American students (n = 90) was assigned to groups based
      on acculturation level. Analysis of variance tests indicated that low
      acculturated, bicultural, and high-acculturated Asian Americans yielded different
      profiles. Compared to a matched White student sample, low-acculturated Asian
      Americans scored significantly higher on 9 scales, and bicultural Asian Americans
      had 6 significantly different scores. These differences were clinically
      interpretable with a range from 6.46 to 21.65 T-score points. High-acculturated
      Asian Americans did not differ from Whites. Cultural variables to be considered
      when interpreting Asian American profiles are discussed.

PMID- 10879353
TI  - Further exploration of the Rorschach Aggressive Content (AgC) variable.
AB  - Based on the recommendations of Baity and Hilsenroth (1999), this study further
      investigated the reliability and validity of the Rorschach Aggressive Content
      (AgC) variable developed by Gacono and Meloy (1994). Eighty-five aggressive
      objects identified by Gacono and Meloy, 19 potentially aggressive objects and 22
      neutral (nonaggressive) objects were rated for aggressiveness based on the
      definition of AgC. Two hundred seventy-six participants rated objects on the
      Object Rating Scale (0-6), where a score of 0 indicates that an object does not
      fit the definition of AgC. In addition, objects rated a 4 (moderately aggressive)
      or higher were then classified into 5 qualitative groupings (weapons, animal/part
      of animal, environmental danger, fictional creature, and other). Analysis of the
      results indicates that the AgC list can be replicated and that objects rated as
      at least moderately aggressive (4) can be reliably classified into distinct
      categories. One-month test-retest reliability (r = .99) suggests that objects can
      be scored consistently using the definition of AgC and provides support for the
      utility of the AgC variable. Based on the results of this study, recommendations
      for the addition of the AgC variable to the list of content categories of Exner's
      (1993) Comprehensive System are presented and discussed along with scoring
      examples.

PMID- 10879354
TI  - Outcome Questionnaire: item sensitivity to change.
AB  - Although high levels of reliability are emphasized in the construction of many
      measures of psychological traits, tests that are intended to measure patient
      change following psychotherapy need to emphasize sensitivity to change as a
      central and primary property. This study proposes 2 criteria for evaluating the
      degree to which an item on a test is sensitive to change: (a) that an item
      changes in the theoretically proposed direction following an intervention and (b)
      that the change measured on an item is significantly greater in treated than in
      untreated individuals. Outcome Questionnaire (Lambert et al., 1996) items were
      subjected to item analysis by examining change rates in 284 untreated control
      participants and in 1,176 individuals undergoing psychotherapy. Results analyzed
      through multilevel or hierarchical linear modeling suggest the majority of items
      on this frequently used measure of psychotherapy outcome meet both criteria.
      Implications for test development and future research are discussed.

PMID- 10879355
TI  - Construct validity of the Psychopathic Personality Inventory in a correctional
      sample.
AB  - The relations between the Psychopathic Personality Inventory (PPI; Lilienfeld &
      Andrews, 1996) and 4 theoretically related constructs (empathy, aggression, work
      ethic, and borderline personality disorder) were examined. Additionally, the
      relation between the PPI and heroism was explored. One hundred male inmates were
      administered the PPI, the Questionnaire Measure of Emotional Empathy (Mehrabian &
      Epstein, 1972), the Aggression Questionnaire (Buss & Perry, 1992), the Protestant
      Ethic Scale (Mirels & Garrett, 1971), the Self-Report for Borderline Personality
      Scale (Oldham et al., 1985), and the Activity Frequency Inventory (Lilienfeld,
      1998). As predicted, the PPI was significantly negatively correlated with empathy
      and significantly positively related to aggression and borderline personality.
      Contrary to prediction, the correlation between the PPI and work ethic was not
      significant. Eight of 11 hypotheses regarding the relations of the PPI subscales
      to these 4 constructs were corroborated. Results support the construct validity
      of the PPI in a correctional sample. The exploratory analysis of the relation
      between the PPI and heroism revealed no significant relations.

PMID- 10879356
TI  - Development of an Infrequency-Psychopathology scale for the MMPI-A: the Fp-A
      Scale.
AB  - This article describes the development and initial validation of the Infrequency
      Psychopathology scale, Fp-A, for the MMPI-A (Butcher et al., 1992). The scale
      parallels the Infrequency-Psychopathology scale, F(p), that has been developed
      for the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). Results
      demonstrated that the 40-item Fp-A scale is superior to the F scale at
      discriminating between faking-bad and accurate reports of psychopathology,
      although the improvement over F was modest, particularly when compared to the
      improvement found for the F(p) scale. The difference seemed to reflect the
      superiority of the MMPI-A F scale to the MMPI-2 F scale. Even so, the findings
      suggest that the identification of overreporting on the MMPI-A could potentially
      be enhanced by using Fp-A as an adjunct to the F scale.

PMID- 10879357
TI  - Inventory of interpersonal problems: a three-dimensional balanced and scalable 48
      item version.
AB  - Interpersonal relating has been a focus of attention in psychiatry for decades.
      To address this domain, a self-rating scale, the Inventory of Interpersonal
      Problems (IIP; Horowitz, Rosenberg, Baer, Ureno, & Villasenor, 1988), was
      developed. Analysis of the psychometric properties of IIP presented in this
      article was performed by principal component analysis (PCA) for the purpose of
      obtaining subscales with a balanced, bipolar dimensionality. The model was
      validated by the resulting dimensions' ability to discriminate among different
      categories of personality disorders (PDs). The problem of a General Complaint
      factor affecting PCAs of questionnaires such as the IIP is discussed thoroughly,
      and ways of avoiding the problem are outlined. We present a three-dimensional
      structure of the IIP with both theoretically appealing and statistically robust
      dimensions of Assertiveness, Sociability, and Interpersonal Sensitivity based on
      48 (out of 127) items. Balanced, additive indexes using the subset of 48 items
      appeared psychometrically sound by showing much lower correlations internally and
      less confounding from the General Complaint factor than extant indexes derived
      from the IIP. External validity seemed to be bolstered by all subscales'
      discriminating significantly between different PDs versus no PDs, on both cluster
      and single diagnosis levels. Our analysis seemed to substantiate the reliability
      (scalability) of three dimensions of the IIP tapping different areas of the
      interpersonal relational field.

PMID- 10879358
TI  - Surviving roots of trauma: prevalence of silent signs of sex abuse in patients
      who recover memories of childhood sex abuse as adults.
AB  - Recent research suggests that victimization imagery is chronically accessible in
      sex-abused populations, which is helpful in distinguishing them from nonabused
      populations. Eight categories of victimization imagery were selectively activated
      by Rorschach stimuli. These 8 sex-abuse signs were replicated in a new sample of
      36 patients with continuous memory of sex abuse. Classification accuracy was 83%.
      By contrast, these signs were present in only 4% (5 of 115) of the protocols of
      nonabused patients. Taken together, the 2 studies confirm reasonably high
      sensitivity of the 8 signs for sex-abused populations and high specificity for
      nonabused populations. The 8 signs were also differentially salient for patients
      who recovered memory of childhood sexual trauma as adults. The Rorschach
      protocols of 59 of 114 patients with delayed recall of sexual abuse possessed
      signs of sex abuse. There was no linkage between therapy and recovered-memory
      cases with and without sex-abuse signs. Emergence of trauma memories was not
      uniquely traceable to treatment. Memories arose outside of the context of therapy
      in over 56% of the cases. Implications for the false-memory debate are discussed.

PMID- 10879359
TI  - Deconstructing dependency in a five-factor world: a meta-analytic review.
AB  - Meta-analysis of studies assessing the relation between interpersonal dependency
      test scores and five-factor model (FFM) domain scores revealed that dependency
      scores are positively correlated with FFM Neuroticism and Agreeableness scores
      and negatively correlated with FFM Extraversion, Openness, and Conscientiousness
      scores. The magnitudes of these correlations were all in the small-to-moderate
      range, and comparable score intercorrelations were obtained when participants'
      dependency levels were assessed by means of a trait dependency questionnaire,
      dependent personality disorder questionnaire, or dependent personality disorder
      interview. These findings have implications for researchers' efforts to
      deconstruct dependency into its basic trait elements and for the dimensional
      approaches to personality disorders being considered for future versions of the
      Diagnostic and Statistical Manual of Mental Disorders.

PMID- 10879360
TI  - The critical need to capture what nurses do.

PMID- 10879361
TI  - Review of research studies that evaluated the impact of treatment for childhood
      cancers on neurocognition and behavioral and social competence: nursing
      implications.
AB  - ISSUES AND PURPOSE: Given the increasing incidence of childhood cancer,
      increasing survivor rates, and documented incidence of sequelae, nurses need
      evidence on which to base interventions for families at risk. The authors review
      and critique research studies that evaluated the impact of treatment for
      childhood cancers. Implications for nursing practice are discussed. CONCLUSIONS:
      Research to evaluate the effects of treatment on neurocognition and behavioral
      and social competency of children with cancer has produced conflicting results.
      Most studies found deleterious effects on all three areas associated with
      childhood cancer treatment. Some studies, however, found no differences between
      childhood cancer survivors and children on therapy compared to normative data or
      healthy controls. PRACTICE IMPLICATIONS: Knowledge of the short- and long-term
      impact of treatment for childhood cancer on neurocognition and behavioral and
      social competence allows nurses to design interventions that mitigate
      neurocognitive effects, decrease behavioral problems, and improve social
      competence.

PMID- 10879362
TI  - Using distraction to reduce reported pain, fear, and behavioral distress in
      children and adolescents: a multisite study.
AB  - ISSUES AND PURPOSE: Distraction during painful procedures has been shown to be
      effective in previous studies, yet this simple intervention is not used
      routinely. This study examined the effectiveness and feasibility of distraction
      in reducing behavioral distress, pain, and fear during venipuncture or
      intravenous insertion. DESIGN AND METHODS: A two-group randomized design with 384
      children in 13 children's hospitals. RESULTS: Age was a significant factor in
      observed behavioral distress, reports of fear, and self-reported pain. The use of
      a kaleidoscope, however, did not significantly reduce pain or distress during
      venipuncture or i.v. insertion. PRACTICE IMPLICATIONS: Failure of the distraction
      intervention to reach statistical significance in this study is puzzling, given
      anecdotal reports of clinical efficacy. Methodological issues may have obscured
      actual differences between experimental and control groups.

PMID- 10879363
TI  - Dog bites in children treated in a pediatric emergency department.
AB  - ISSUES AND PURPOSE: Unintentional injury is the leading cause of death and
      disability among children. This study sought to describe the characteristics of
      dog bite injuries to aid in promoting healthy environments for children. DESIGN
      AND METHODS: This descriptive, retrospective study of one hospital's 1997
      emergency department records detailed dog bite injuries to children and
      adolescents and resultant emergency treatment (N = 204). RESULTS: Children < or =
      5 years of age accounted for 49% of the injuries. The biting dog's owner was
      generally a parent or neighbor. Only 2 children received rabies prophylaxis.
      PRACTICE IMPLICATIONS: Parents and children need information about safe
      interactions with dogs, including community leash laws and quarantine guidelines.
      Nurses should know the procedures for reporting dog bite injuries to local health
      authorities. Interested nurses can find many opportunities to assist with
      community safety campaigns.

PMID- 10879364
TI  - Family-centered care when abuse or neglect is suspected.

PMID- 10879365
TI  - We are all advocates.
AB  - As pediatric nurses, we have many opportunities to advocate for children and
      often have more resources and more knowledge about children and advocacy than we
      realize. It is what we do. There are many issues and many ways to advocate. I
      encourage you to use the ideas presented here and the listed resources to enhance
      your current advocacy efforts. Become politically active. Connect to state and
      local groups by either membership, letter writing, or the Internet.

PMID- 10879366
TI  - Seeking early care: the role of prenatal care advocates.
AB  - This exploratory study investigates the role of social support in the initiation
      of prenatal care by analyzing data from interviews with 36 pregnant women at a
      public health facility in Tuscaloosa, Alabama. A systematic sample of U.S.-born
      women aged 19 to 34 who initiated care in each of the three trimesters was
      interviewed. After controlling for age and education, three variables were found
      to be associated with earlier estimated gestational age at the time of a woman's
      first prenatal visit: self-referral to care, more prenatal care advocates, and
      fewer children. There was no significant effect on the timing of entry to care
      associated with ethnicity, marital status, transportation availability, rural vs.
      urban residence, distance of residence from the clinic, or prior prenatal care at
      the public health facility. These results suggest that first-time mothers are
      likely to seek early care and that family and friends play a significant support
      role in encouraging women to begin care.

PMID- 10879367
TI  - Preparing for motherhood: authoritative knowledge and the undercurrents of shared
      experience in two childbirth education courses in Cagliari, Italy.
AB  - This article compares the social settings and teaching organization of two
      differently structured childbirth education courses in Cagliari, Italy, in order
      to understand how social processes and contexts work to negotiate authoritative
      knowledge. Although the explicit goal of both courses was to transmit biomedical
      knowledge, knowledge based in women's experience nonetheless dominated some
      course sessions. Thus, I examine the social processes and interactions that
      enabled women's experiential knowledge to dominate discussions and subsequently
      share in the authority of biomedical knowledge in some situations. Because few
      existing studies do so, this article also addresses a gap in our current
      understanding by exploring not only how experiential knowledge comes to share
      authority with biomedical knowledge, but also, why it is important that it does.
      Focusing on the efficacy of differently structured courses, this article informs
      the planning of future childbirth education courses in similar settings.

PMID- 10879368
TI  - Sterilizing vaccines or the politics of the womb: retrospective study of a rumor
      in Cameroon.
AB  - In 1990 a rumor that public health workers were administering a vaccine to
      sterilize girls and women spread throughout Cameroon. Schoolgirls leapt from
      windows to escape the vaccination teams, and the vaccination campaign (part of
      the Year of Universal Child Immunization) was aborted. This article traces the
      origin and development of this rumor. Theories of rumor and ambiguous cultural
      response to new technologies shed some light on its genesis and spread, but
      explain neither its timing nor its content. For this task we need to examine the
      historical context of Cameroonian experience with colonial vaccination campaigns
      and the contemporary contexts of the turmoil of democratization movements and
      economic crisis, concurrent changes in contraceptive policy, and regional
      mistrust of the state and its "hegemonic project." Drawing on Bayart's politique
      du ventre and White's thoughts on gossip, we explore this rumor as diagnostic of
      local response to global and national projects. This response, expressed in this
      case through the idiom of threats to local reproductive capacity, reveals a
      feminine side to local-global relations, a politics of the womb.

PMID- 10879369
TI  - Pluralism and pragmatism: knowledge and practice of birth in Morocco.
AB  - This article examines knowledge and practice surrounding birth in Morocco, using
      women's narratives of their recent birth experiences, observations of medical
      encounters, and statements about prescribed behaviors during pregnancy and birth,
      as well as the vocabulary used to refer to physiological processes, disease
      conditions, and social relationships. The analysis shows that the three major
      themes that define the traditional Moroccan ethnophysiology of birth--conceptions
      of hot and cold, the symbolism of blood, and the metaphors of openness and
      obstruction--are not inconsistent with the precepts of biomedicine and public
      health and do not in themselves constitute obstacles either to safe home births
      or the use of formal health services. Women integrate biomedical and local
      knowledge and practices and simultaneously seek care from "traditional" and
      "modern" practitioners, creatively combining elements in accordance with their
      situations and the means at their disposal. Birth narratives show the eclecticism
      and flexibility that characterize women's attitudes and behaviors regarding
      pregnancy and birth. Women's decisions are shaped by two overriding
      considerations: incertitude about what can happen during the last phase of a
      pregnancy and ambivalence toward the available alternatives for care, both of
      which reflect a realistic assessment of their situations. By showing how women
      make decisions in response to these considerations, this article seeks to clarify
      some of the links between beliefs and practices and to contribute to ongoing
      discussions regarding the relevance of local knowledge for patterns of health
      care.

PMID- 10879370
TI  - W.H.R. Rivers Graduate Prize Essay (1996). "Imperfect angels" : narrative
      "emplotment" in the medical management of children with craniofacial anomalies.
AB  - This article uses the paradigm of "therapeutic emplotment" to investigate the
      medical management of children with facial disfigurements at a craniofacial
      anomalies center in Northern California. Data are observations of, and
      semistructured interviews with, plastic surgeons, nurses, geneticists,
      orthodontists, and other medical professionals who composed the craniofacial
      anomalies team. Team members perceived that children feel socially stigmatized by
      their disfigurements. These medical professionals adjusted their own behavior
      according to these perceptions. They "emplotted" their actions, using the theme
      that disfigured children are attractive and worthy of attention and affection.
      Medical professionals attempted to depersonalize and neutralize the symbolically
      loaded disfigurements through the use of clinical language in an attempt to
      "separate" the child from his or her facial anomaly. The range of styles and
      approaches to interaction was diverse and varied in effectiveness, suggesting
      that some medical professionals were more skilled at emplotment than others.

PMID- 10879371
TI  - Caretakers, child care practices, and growth failure in highland Ecuador.
AB  - Problems for child health have been attributed to child and sibling caretaking.
      Nevertheless, our data from highland Ecuador suggest an ambiguous relationship
      between growth failure and the practice of peer care. In a region where levels of
      chronic undernutrition as measured by stunting exceed 75 percent and fully one
      quarter of children under five are underweight, analysis of structured
      observations of a sample of 28 children reveals no statistical association
      between growth indices and the practice of older children caring for younger
      children. Qualitative data, however, indicate that the practice can be a
      complication in specific cases where children already suffer compromised health.
      While the advantages or disadvantages associated with particular caretakers
      appear secondary to the risks attending inadequate diets or the broader
      environment of rural poverty, the potential for difficulties to emerge from peer
      care suggests that community day care provides a valuable alternative in this
      context.

PMID- 10879372
TI  - Parallel and divergent landscapes: cultural encounters in the ethnographic space
      of Tuareg medicine.
AB  - This essay explores the dialogue between the local quest for healing and the
      anthropological quest for healing knowledge, and local assessments of knowledge
      power relationships in these processes. The context is medical discourse among
      the Tuareg of Niger Republic, West Africa, and my research experiences among
      these people. I examine local medical specialists and their traditional and
      changing practice in terms of how they perceive and respond to wider knowledge
      and power systems that impinge on local health care. Paramount in these systems
      are central state policies and medical anthropological research on healing, as
      these intersect in a postcolonial and post-separatist/rebellion setting. The
      essay analyzes parallels between the exchange of medicine and the exchange of
      knowledge and reflects upon how anthropological knowledge of African healing
      systems is constructed in an environment highly charged with power and danger--of
      political violence and economic crisis. The broader issue addressed here is how
      to give greater empowerment to local residents' voices in their "indigenous
      critique" of the medical anthropological project.

PMID- 10879373
TI  - Salivary gland tumours.

PMID- 10879374
TI  - Quality-of-life in pacemaker and implantable cardioverter defibrillator
      recipients.

PMID- 10879375
TI  - Patients' attitudes toward implanted defibrillator shocks.
AB  - In addition to its beneficial effect on patient survival, the implanted
      cardioverter defibrillator (ICD) changes a patient's life physically, socially,
      and psychologically. For improved patient management, it is important to
      understand the quality-of-life changes that accompany this mode of treatment. To
      this end, 119 patients were surveyed retrospectively and interviewed concurrently
      regarding their emotional, physical, and behavioral responses to ICD shocks and
      to the device itself. Most (55%) correctly estimated the total number of shocks
      they had received within a 10% margin. They found the shocks severe, 79%
      assigning a score between 3 and 5 on a scale of 1-5. Common descriptions of the
      shock sensation were a blow to the body or a spasm causing the entire body to
      jump. Most patients tolerated the shocks as lifesaving, but 23% dreaded shocks
      and 5% even said they would rather be without the ICD and take their chances.
      After a shock, 50% of patients called their physician and 42% continued their
      daily routine. Thirty percent went to a hospital emergency room or called a
      rescue service. Sixty-five percent had no preshock prodromes. Fifty-four percent
      were interested in the programmable option of a warning signal prior to a shock,
      while 31% preferred no warning. Of the 74% who were advised not to drive after
      implantation, 29% drove anyway. Five patients were shocked while driving with no
      resulting accidents. We conclude that most patients find ICD shocks moderately
      uncomfortable, but they tolerate them because of the lifesaving protection
      provided by the device.

PMID- 10879376
TI  - Assessing the psychosocial impact of the ICD: a national survey of implantable
      cardioverter defibrillator health care providers.
AB  - The implantable cardioverter defibrillator (ICD) provides a survival advantage
      over antiarrhythmic medications for patients with life-threatening ventricular
      arrhythmias. However, the effect of ICD therapy on quality-of-life and
      psychosocial functioning are not as well understood. Health care providers (e.g.,
      physicians, nurses) can serve as a valuable source of information related to
      these ICD outcomes. The purpose of this study was to investigate health care
      provider perceptions regarding: (1) the quality-of-life and psychosocial
      functioning of their ICD recipients, (2) the concerns or problems reported by ICD
      recipients, and (3) the degree of provider comfort in managing these concerns.
      The final sample of health care providers (n = 261) rated ICD recipients' global
      quality-of-life and psychosocial functioning, and specific concerns about health
      care, lifestyle, special population adjustment, marital and family adjustment,
      and emotional well-being. With regard to quality-of-life, health care providers
      reported that the majority of ICD recipients were functioning better (38%) or
      about the same (47%) than before implantation. However, health care providers
      reported that 15% of recipients experienced worse quality-of-life
      postimplantation. Similarly, health care providers indicated that 10%-20% of ICD
      recipients experienced worse emotional functioning and strained family
      relationships. Moreover, issues related to driving, dealing with ICD shocks, and
      depression were the most common ICD recipient concerns. Significant differences
      were noted between physicians and nurses/other health care professionals on a
      wide range of psychosocial issues. Health care providers generally reported the
      most comfort dealing with traditional medical issues (i.e., patient adherence),
      and the least comfort in managing emotional well-being issues (e.g., depression
      and anxiety). These results suggest that routine attention to ICD quality-of-life
      and psychosocial outcomes is indicated for health care providers who care for ICD
      recipients.

PMID- 10879377
TI  - Quality-of-life of pacemaker patients: a reappraisal of current instruments.
AB  - Current clinical practice permits the use of single chamber ventricular or dual
      chamber pacemakers. However, it is not known which type of pacemaker results in
      superior clinical and patient outcomes. This is of growing importance because of
      the higher costs and increased risk of technical failures of dual chamber
      pacemakers. Patient outcomes can be assessed with quality of life questionnaires,
      but it is unclear which questionnaires are valid for use in pacemaker patients.
      This article reappraises studies on quality of life instruments for pacemaker
      patients. We searched MEDLINE (1985-1998) for studies assessing quality-of-life
      in general and in pacemaker patients. The SF-36 appeared to be the best among
      generic questionnaires because of its psychometric characteristics and experience
      of use. Concerning disease specific instruments, the Karolinska quality of life
      questionnaire has desirable content validity but lacks more rigorous psychometric
      validation, which constitutes a serious limitation. Previous studies suggested
      that implantation of atrioventricular pacemakers improves quality-of-life
      compared to ventricular pacemakers, but since no well-designed and validated
      questionnaire exists, these results should be interpreted with caution. The best
      outcome measure to evaluate quality-of-life in pacemaker patients would be a
      combination of a generic health profile with established reliability and validity
      supplemented with a cardiovascular assessment adjusted to suit pacemaker
      patients. By doing so, individual scores can be compared within a disease cohort
      and to same-aged, nondiseased persons, as well as other diseased populations. The
      development and validation of such an instrument is currently needed.

PMID- 10879378
TI  - A cardiac evoked response algorithm providing threshold tracking: a North
      American multicenter study. Clinical Investigators of the Microny-Regency
      Clinical Evaluation Study.
AB  - The purpose of this study was to evaluate a pacing system using the recognition
      of cardiac evoked response for the automatic adjustment of pacing output.
      Patients were prospectively followed after primary implantation of VVIR
      pacemakers using AutoCapture (St. Jude Medical CRMD). Sensing and pacing
      thresholds, polarization signal, evoked response, and AutoCapture performance
      were evaluated with serial visits and 24-hour Holter monitoring. Three hundred
      ninety-eight patients (mean age 71 +/- 15 years) were followed for an average
      duration of 1 year (3 days-1.75 years) with the algorithm functional in > 90% of
      patients. Backup pacing in the event of exit block was confirmed in all patients.
      Pacing thresholds remained stable at 0.89 +/- 0.34 V with a pulse width of 0.31
      ms (with chronic output autoset at 0.3 V above the actual threshold). Evoked
      response exhibited a small but statistically significant increase with time (8.92
      mV at implant, 9.60 mV at 12 months), however, this finding did not result in any
      change in AutoCapture function during our follow-up period. The polarization
      signal remained stable with minimal variation (1.12 mV at implant, 1.18 at 12
      months). No clinical adverse events were observed using the AutoCapture
      algorithm. In this initial experience with the AutoCapture algorithm the evoked
      response and polarization measurements remained adequate, allowing the system to
      function in the majority of patients with safe, low output pacing. High energy
      backup pacing provided an added safety feature over fixed output devices in cases
      of unexpected threshold rises. Longer follow-up is required for continued long
      term validation of the algorithm.

PMID- 10879379
TI  - Action potential remodeling in the human right atrium with chronic lone atrial
      fibrillation.
AB  - It has been shown in animal experiments that recurrent induction of atrial
      fibrillation (AF) or long-lasting atrial pacing causes a shortening of the atrial
      effective refractory period (ERP) and action potential duration (APD) and a loss
      of their physiological adaptation to rate. Much remains to be clarified as to the
      electrical remodeling in human patients with chronic AF. We recorded monophasic
      action potentials (MAPs) from the right atrium at pacing cycle lengths (CLs) of
      300, 333, 400, 500, 600, and 750 ms after external cardioversion in 13 patients
      with chronic lone AF. Their configuration was compared with those obtained from
      13 control patients. APDs at 50% and 90% repolarization (APD50, APD90) at the
      shortest CL (300 ms) in control and AF patients were 131 +/- 14, 211 +/- 19 ms
      and 136 +/- 12, 210 +/- 22 ms, respectively (mean +/- SD). APDs in control
      patients increased linearly with increases of CL, reaching maximal values of 174
      +/- 30 ms (APD50) and 277 +/- 38 ms (APD90) at a CL of 750 ms. In AF patients,
      the steady-state CL-APD relation was shifted downward and flattened at CLs > 500
      ms; APD50 and APD90 at a CL of 750 ms were 158 +/- 19 ms, 232 +/- 28 ms,
      respectively. APD90s at CLs of 600 and 750 ms were significantly shorter in AF
      than in control patients. No statistically significant difference was obtained in
      APD50 between the two groups at any CL tested. MAP configuration in AF patients
      was characterized by an acceleration of the late repolarization. The difference
      between APD90 and APD50 (APD90-50) in control patients was increased with
      increases of CL, reaching a plateau at a CL of 600 ms. This CL dependent slowing
      of the late repolarization of MAPs was abolished in AF patients. The atrial ERP,
      measured at CLs of 400 and 600 ms, showed changes parallel to those of APD90. ERP
      at a CL of 600 ms in AF patients (224 +/- 13 ms) was significantly shorter than
      that in control patients (247 +/- 25 ms). We conclude that chronic lone AF leads
      to electrical remodeling in the human atrium, which causes a loss of rate
      response of the late repolarization of action potential, leading to a shortening
      of APD and ERP at slower heart rates.

PMID- 10879380
TI  - A randomized, prospective comparison of anterior and posterior approaches to
      atrioventricular junction modification of medically refractory atrial
      fibrillation.
AB  - To compare the safety and efficacy of anterior versus posterior approach for
      atrioventricular (AV) junction modification, 40 patients with medically
      refractory paroxysmal (PAF) or chronic atrial fibrillation (AF) were randomly
      assigned to receive AV junction modification with an anterior or posterior
      approach. If the ablation session had taken more than 1 hour without success, the
      alternative ablation approach was attempted. Among the 18 patients assigned to
      receive the anterior approach, 14 (78%) had a primary success. One (5%) patient
      had complete AV block after ablation. Three patients crossed over to the
      posterior approach and had a successful outcome. Fourteen (64%) of 22 patients
      initially treated with the posterior approach had primary success. One (4%)
      patient developed complete AV block. Seven patients crossed over to the anterior
      approach and had a successful outcome. The primary success rate (14/18 vs 14/22,
      P = NS), incidence of transient AV block (3/18 vs 3/22, P = NS), and complete AV
      block (1/18 vs 1/22, P = NS) were similar between the anterior approach and
      posterior approach. The major differences between the two groups showed more
      radiofrequency pulses (10 +/- 4 vs 6 +/- 3 pulses, P < 0.01), longer procedure
      duration (50 +/- 24 vs 28 +/- 18 minutes, P < 0.01), and longer fluoroscopy
      exposure time (28 +/- 17 vs 16 +/- 8 minutes, P < 0.01) in the patients who had
      primary success with the posterior approach. In conclusion, this study
      demonstrated that (1) the two techniques had similar efficacies; (2) if one
      approach was ineffective, switching to the other approach might be safe; (3)
      combining these two approaches resulted in overall improvement in the success
      rate of this procedure, and (4) the posterior approach needed more radiofrequency
      pulses, longer procedural time, and longer fluoroscopy exposure time.

PMID- 10879381
TI  - Assessment of autonomic nervous system functions in patients with vitamin B12
      deficiency by power spectral analysis of heart rate variability.
AB  - The purpose of this study was to test the autonomic nervous system function of
      patients with vitamin B12 deficiency (megaloblastic anemia) by measuring heart
      rate variability (HRV). The study population consisted of 17 vitamin B12
      deficient patients and 15 age- and sex-matched normal volunteers. HRV was
      measured by power spectral analysis from which power of the low frequency (LF)
      peak (0.04-0.15 Hz), normalized units of the LF peak (LFNU), power of the high
      frequency (HF) peak (0.15-0.4 Hz), normalized units of the HF (HFNU), and ratio
      of power of LF to power of HF (LF:HF) were calculated. Vitamin B12 deficient
      patients had lower LF, LFNU, HF, HFNU, and LF:HF ratio than normal volunteers (P
      < 0.05). Decreases in sympathetic indices (LF and LFNU) were greater than those
      measured in parasympathetic indices (HF and HFNU). All HRV parameters correlated
      positively with the level of vitamin B12 (P < 0.001) and negatively with the
      duration of disease (P < 0.001). After vitamin B12 replacement the HRV parameters
      of patients and controls became comparable (P > 0.05). Our data suggest that
      autonomic sympathetic and parasympathetic nervous activities are decreased in
      patients with vitamin B12 deficiency, an abnormality that can be corrected by
      vitamin B12 replacement therapy.

PMID- 10879382
TI  - Temporal and geographical trends in indications for implantation of cardiac
      defibrillators in Europe 1993-1998. Medtronic ICD System Investigators.
AB  - Despite the demonstrated efficacy of implantable cardioverter defibrillators
      (ICDs) in reducing sudden and total mortality in selected populations, their
      implantation rates vary greatly between countries. The aim of our study was to
      analyze temporal and geographical trends in ICD implantations in countries with
      similar health related expenditure in Western Europe. A total of 2,257 patients
      from ten European evaluation studies of Medtronic defibrillators and
      defibrillation electrodes, conducted between 1993 and 1998, representing 12
      countries, was included in this analysis. Rates of implantation and clinical
      characteristics were compared between countries and years of implantation. Rates
      of implantation differed greatly between Western European countries and did not
      correlate with indices of health related expenditure (i.e., number of patients
      per physician and number of patients per hospital bed). However, there was a
      strong and statistically significant negative correlation between the use of
      amiodarone and the rates of implantation (r = -0.66, P = 0.02). Temporal trends
      showed a significant increase in the age of the patients receiving an ICD between
      1993 and 1998 (57 +/- 14 vs 61 +/- 12 years, mean +/- SD, P < 0.001). There was
      also a temporal trend towards an increased incidence of coronary artery disease
      and a significant decrease in the incidence of cardiomyopathy. There was a
      temporal increase in implantations in patients with a history of ventricular
      tachycardia. Despite a general scientific agreement that ICDs are a first line
      treatment for patients at high risk of sudden cardiac death, their acceptance
      remains low in several developed countries. This low acceptance may not be
      entirely related to budget constraint but may also be related to their perceived
      efficacy by physicians and health authorities.

PMID- 10879383
TI  - Initial results with left ventricular pacemaker lead implantation using a
      preformed "peel-away" guiding sheath and "side-wire" left ventricular pacing
      lead.
AB  - We report our preliminary experience with the use of preformed "peel-away"
      guiding sheaths and "side-wire" pacing leads for permanent biventricular
      pacemaker insertion in 13 patients with heart failure. Three of these patients
      were undergoing an upgrade of a preexistent VVIR pacing system after prior His
      ablation for medically refractory atrial fibrillation. Six of the patients had
      undergone attempted biventricular pacemaker insertion, but required left
      ventricular lead repositioning after total implantation failure or late
      displacement of the lead. The remaining patients were undergoing new system
      implantation. Target vessel cannulation was achieved in all patients. However, in
      one patient, diaphragmatic pacing throughout the target vessel length prevented
      successful implantation. All other implants were ultimately successful (92%
      success rate). We conclude that device implantation using a preformed sheath and
      side-wire pacing lead is feasible and may offer significant benefits over
      implantation with currently available technology.

PMID- 10879384
TI  - Permanent pacemaker therapy before and after the reunification of Germany: 16
      years of experience at an East German regional pacing center.
AB  - The reunification of Germany had a significant influence on the management of
      patients with bradyarrhythmias. The current study was performed in a regional
      pacing center located in the former German Democratic Republic. It compares the
      situation of patients with critical bradyarrhythmias before and after the
      reunification of Germany in 1990 focusing on (1) indication for pacemaker
      implantation, (2) pacemaker modalities and function, (3) type of leads, (4)
      frequency of reintervention, and (5) early and late complications. The study
      covers 9 years before and 7 years after the reunification. A total of 1,125
      patients were included, and the database was formed by the patients' files and
      the protocols of implantation. The situation before reunification was
      characterized by a nonavailability of modern physiological pacing devices and
      insufficient diagnostic equipment. Between 1981 and 1990, 384 patients underwent
      pacemaker implantation solely receiving single chamber devices with no or only
      minimal feasibility of programming. Between 1990 and 1996, 741 patients were
      treated, and they all received modern pacemakers having the capability of
      multiprogramming and telemetry. Regarding complications of pacemaker therapy,
      lead related problems significantly decreased after the reunification
      (dislocation, 5.3% vs 1.7%, P < 0.05; exit block, 6.7% vs 1.4%, P < 0.05)
      opposite to pacemaker infections, which significantly increasing after dual
      chamber pacemakers were implanted (2.2% vs 6.0%, P < 0.05). The reunification of
      Germany dramatically improved the situation of patients with critical
      bradyarrhythmias leading to free access to high-tech pacing equipment within a
      few months. However, the abrupt change from antiquated to modern pacemaker
      therapy created some new problems, especially regarding application and handling
      of modern physiological pacing devices.

PMID- 10879385
TI  - Safety of pacemaker implantation prior to radiofrequency ablation of
      atrioventricular junction in a single session procedure.
AB  - RF current delivery may cause acute and chronic dysfunction of previously
      implanted pacemakers. The aim of this study was to assess prospectively the
      effects of RF energy on Thera I and Kappa pacemakers in 70 consecutive patients
      (mean age 70 +/- 11 years, mean left ventricular ejection fraction 48 +/- 15%)
      who underwent RF ablation of the AV junction for antiarrhythmic drug refractory
      atrial fibrillation (permanent in 42 patients, paroxysmal in 28). These pacing
      systems incorporate protection elements to avoid electromagnetic interference.
      The pacemakers (Thera DR 7960 I in 20 patients, Thera SR 8960 I in 30, Kappa DR
      600-601 in 8, Kappa SR 700-701 in 12) were implanted prior to RF ablation in a
      single session procedure and were transiently programmed to VVI mode at a rate of
      30 beats/min. Capsure SP and Z unibipolar leads were used. During RF application
      there was continuous monitoring of three ECG leads, endocavitary electrograms,
      and event markers. Complete AV block was achieved in all cases after 3.6 +/- 2.9
      RF pulses and 100 +/- 75 seconds of RF energy delivery. The mean time of
      pacemaker implantation and RF ablation was 60 +/- 20 minutes. Transient or
      permanent pacemaker dysfunction including under/oversensing, reversion to a
      "noise-mode" pacing, pacing inhibition, reprogramming, or recycling were not
      observed. Leads impedance, sensing, and pacing thresholds remained in the normal
      range in the acute and long-term phase (average follow-up 18 +/- 12 months). In
      conclusion, Thera I and Kappa pacemakers exhibit excellent protection against
      interference produced by RF current. The functional integrity of the pacemakers
      and Capsure leads was observed in the acute and chronic phases. Thus, the
      implantation of these pacing systems prior to RF ablation of the AV junction can
      be recommended.

PMID- 10879386
TI  - Long-term superiority of steroid elution in atrial active fixation platinum
      leads.
AB  - Steroid elution reduces the acute increase in stimulation threshold particularly
      in active fixation leads. The aim of this study was to investigate the long-term
      efficacy of steroid elution in atrial screw-in leads compared to conventional
      lead design. Two different bipolar active fixation platinum lead designs were
      implanted. Leads were similar except for the presence (group S, n = 66) or
      absence (group N, n = 68) of steroid elution. Patients received dual chamber
      pacemakers with the following atrial leads in consecutive order: Medtronic 4058 M
      (group N, n = 30), Medtronic 4068 (group S, n = 40), Vitatron IMS 13 (identical
      to 4058 M, group N, n = 38), and Vitatron IMX 13 (identical to 4068, group S, n =
      26). The mean follow-up period was 40.7 +/- 16.1 months (range 10 to 84 months).
      Stimulation thresholds, pacing impedances, P wave potentials, and sensing
      threshold were assessed for both groups immediately, 10 days, 6 weeks, and 3
      months after implantation followed by 6-months intervals. Energy thresholds,
      chronaxie-rheobase products, and energy consumption of atrial pacing were
      calculated. Chronic values were deduced from the most recent measurement
      performed in an individual patient. Within the first 10 days after implantation,
      atrial voltage threshold at pulse duration of 0.4 ms increased from 0.91 +/- 0.42
      to 2.06 +/- 0.45 V in group N (P < 0.001). Less increase was observed in group S
      (0.83 +/- 0.39 to 1.08 +/- 0.53 V, P = 0.003). Atrial voltage thresholds remained
      markedly lower in steroid-eluting leads during whole follow-up (1.12 +/- 0.49 V
      in group S vs 1.58 +/- 0.71 V in group N, P < 0.001). Chronic energy consumption
      was markedly reduced in group S (4.0 +/- 2.7 microJ) compared to group N (9.8 +/-
      7.5 microJ, P < 0.001). An atrial voltage threshold below 1.25 V at 0.4 ms was
      achieved in 92.3% of patients of group S allowing programming of an output of 2.5
      V. Such low outputs were feasible in only 49.3% of patients in group N (P <
      0.001). Chronic P wave amplitudes did not differ significantly between groups
      (3.27 +/- 1.81 mV in group N vs 3.24 +/- 1.18 mV in group S, P = 0.91). Steroid
      elution diminishes the increase of stimulation thresholds of nonsteroid atrial
      active fixation platinum leads resulting in a long-term reduction of energy
      consumption. Thus, use of steroids can be recommended for general use in atrial
      active fixation lead designs.

PMID- 10879387
TI  - Multiple adverse events with a dual chamber pacemaker.
AB  - The aim of the study was to evaluate our experience with Physiocor 400T, a dual
      chamber unipolar pacemaker manufactured by Sorin Biomedica. Between March 1993
      and December 1994, 63 units of that model were implanted at our center. Patients
      were followed for 46 +/- 16 months. By the end of follow-up, 15 patients had
      died, 1 patient was lost to follow-up, and two units had been replaced for
      unrelated reasons. During follow-up the following phenomena had been observed:
      (1) Spontaneous backup reversion (VOO, 80 ppm) in 6 (9.5%) of 63 patients. In
      three patients this phenomenon was accompanied by concomitant ineffective pacing
      artifacts at 130 beats/min with very low pulse widths. (2) Unexpected battery
      depletion (EOL) occurred in 3 (5%) of 63 patients; two of the three occurred
      within weeks of routine evaluation that confirmed normal battery status. (3)
      Early elective replacement time (ERT) unpreceded by a gradual drop in magnet rate
      in 2 (3.2%) of 63 patients. (4) Total loss of telemetry without change in pacing
      mode in 1 (1.6%) of 63 patients. The estimated event-free 5-year survival of this
      model was 46%. In conclusion, 12 (19%) of 63 patients had adverse events with
      Physiocor 400T pacemakers. The potential risk of asynchronous pacing for
      prolonged periods and the risk of unexpected EOL warrants consideration of
      elective replacement of all remaining units.

PMID- 10879388
TI  - Failure of coronary sinus pacing in reducing local atrial conduction delay in
      patients with atrial fibrillation after successful internal cardioversion.
AB  - Recent studies suggested that distal coronary sinus (CS) pacing may prevent
      atrial fibrillation (AF) by reducing site dependent intraatrial conduction delay.
      The aim of this study was to investigate the effect of high right atrial (HRA)
      and distal CS pacing on local conduction delay in patients with AF. The study
      population consisted of 10 patients with persistent AF after transvenous atrial
      defibrillation and 10 control subjects. The local conduction delays along the
      anterolateral right atrium (RA), in the CS, and at the right atrial septum (RAS),
      and the incidence of AF in response to an atrial extrastimulus during HRA and
      distal CS pacing at a drive cycle length of 400, 500, and 600 ms were evaluated.
      In patients with AF, distal CS and HRA pacing are associated with more prominent
      and similar extent of conduction delay within the atria, without any significant
      difference in the dispersion of conduction delay and susceptibility to AF
      induction (70% vs 60%, P = 0.9). In normal controls, distal CS pacing reduces the
      conduction delay at the RAS and CS ostium and decreases the dispersion of
      conduction delay and the propensity for AF induction (0% vs 50%, P = 0.03)
      compared to HRA pacing. The pacing drive cycle length has no significant effect
      on conduction delay in patients with AF and normal controls (P > 0.05). Compared
      to normal controls, patients with AF have significantly longer conduction delay
      at the RAS and along the anterolateral RA during HRA and distal CS pacing. The
      result of this study demonstrates that the effect of HRA and distal CS pacing on
      the local atrial conduction delay in patients with and without AF differ
      significantly. These patients with AF may have more diffuse atrial anisotropy
      causing the changes in conduction, and pacing from distal CS in these patients
      dose not reduce the propensity for AF.

PMID- 10879389
TI  - The 1998 NASPE prospective catheter ablation registry.
AB  - The results of the NASPE Prospective Voluntary Registry are reported. A total of
      3,357 patients were entered. For those undergoing atrioventricular (AV)
      junctional ablation (646 patients), the success rate was 97.4% and significant
      complications occurred in 5 patients. A total of 1,197 patients underwent AV
      nodal modification for AV nodal reentrant tachycardia, which was successful in
      96.1% and the only significant complication was development of AV block (1%).
      Accessory pathway ablation was performed in 654 patients and was successful in
      94%. Major complications included cardiac tamponade (7 patients), acute
      myocardial infarction (1 patient), femoral artery pseudoaneurysm (1 patient), AV
      block (1 patient), pneumothorax (1 patient), and pericarditis (2 patients). A
      total of 447 patients underwent atrial flutter ablation and acute success was
      achieved in 86% of patients. Significant complications included inadvertent AV
      block (3 patients), significant tricuspid regurgitation (1 patient), cardiac
      tamponade (1 patient), and pneumothorax (1 patient). Atrial tachycardia was
      attempted for 216 patients and the success rate was higher for those with right
      atrial (80%) or left atrial (72%) compared to those with septal foci (52%). A
      total of 201 patients underwent ablation for ventricular tachycardia. The success
      rate was higher for those with idiopathic ventricular tachycardia compared to
      those with ventricular tachycardia due to ischemic heart disease or
      cardiomyopathy. While the number of AV junction ablation were higher for those >
      60 years of age, there was no significant difference in the success rate or
      incidence of complication comparing patients > or = 60 to those < 60 years of
      age. In addition, we found no differences in incidence of success or
      complications comparing large volume centers (> 100 ablation/year) with lower
      volume centers or between teaching and non-teaching hospitals.

PMID- 10879390
TI  - Advantages and disadvantages of trial designs: a review of analysis methods for
      ICD studies. AVID Investigators.
AB  - General modalities of analyses that have been used for ICD studies are reviewed.
      Published "typical" examples are briefly described. The historical cohort method
      is exemplified with previously unpublished data from the Seattle Cardiac Arrest
      Survivor database. The AVID Study database is used to compare the results
      obtained from nonrandomized methodologies with randomized methodologies.
      Particular issues related to the use of the ICD for example, mode of death,
      inability to blind, selection practice, and treatment decision times make this a
      natural pedagogic platform.

PMID- 10879391
TI  - A case of recurrent syncope.

PMID- 10879392
TI  - Second sight.

PMID- 10879393
TI  - Adenosine induced monomorphic ventricular tachycardia.
AB  - Polymorphic ventricular tachycardia has been reported following the
      administration of adenosine for the treatment of SVT. We present a case of
      monomorphic ventricular tachycardia in a 75-year-old man following the
      intravenous administration of adenosine for stress testing.

PMID- 10879394
TI  - Assessment of fetal rhythm in complete congenital heart block by
      magnetocardiography.
AB  - We report high precision assessment of fetal rhythm in utero in a case of
      isolated congenital complete heart block using fetal magnetocardiography. The
      recordings reveal a remarkably strong tendency for the atria and ventricles to
      synchronize, which is manifested by the continual presence of ventriculophasic
      sinus arrhythmia and frequent episodes of accrochage and isorhythmic AV
      dissociation.

PMID- 10879395
TI  - False-positive exercise stress electrocardiogram due to accessory pathway in the
      absence of manifest preexcitation.
AB  - False-positive exercise testing in patients with an accessory pathway has been
      described only in patients with manifest preexcitation during exercise. We
      describe a patient in whom marked ST-segment changes were seen during an exercise
      test in the absence of any preexcitation of the QRS complexes. The role of the
      accessory pathway in producing the ST changes was reaffirmed by absence of this
      abnormality following catheter ablation of the accessory pathway.

PMID- 10879396
TI  - Inappropriate shock delivery by implantable defibrillators with dual chamber
      pacing during nonsustained ventricular tachycardia in patients with heart block.
AB  - Transvenous implantable cardioverter defibrillators (ICDs) have improved the
      management of patients with ventricular tachycardia/ventricular fibrillation
      (VT/VF). Many patients with sustained VT/VF have bradyarrhythmias and
      nonsustained VT. Shock delivery due to nonsustained VT would be an undesirable
      feature. Abortive shock capability (noncommitted shocks) is a feature available
      in devices to prevent delivery of shocks for nonsustained VT. Recently, the
      availability of dual chamber pacing capability has improved the efficacy of ICDs
      by obviating the need of separate pacemaker implantation in patients with VT/VF
      and concomitant bradyarrhythmias. However, interaction between bradyarrhythmias
      and VT/VF has not been described and has important clinical implications. We
      report a case in which a patient with complete atrioventricular (AV) block and
      ventricular arrhythmias received an inappropriate shock following spontaneous
      termination of nonsustained VT, showing an important shortcoming of devices with
      these features.

PMID- 10879397
TI  - Use of an implantable cardioverter defibrillator in a patient with two implanted
      neurostimulators for severe Parkinson's disease.
AB  - We report a patient with Parkinson's disease treated with two pectorally
      implanted neurostimulators (NSs) who presented with a life-threatening
      ventricular tachyarrhythmia in whom an abdominal ICD was implanted. Testing
      during implantation showed that the NS did not affect the bipolar sensing of the
      ICD, even when the NSs were set at a frequency of 130 pulses/s with an output of
      5 V and pulse width of 0.21 ms in a bipolar and a unipolar configuration. The ICD
      shock, however, did affect both NSs: there was a reset to the output Off state
      and there was a reset of the electrode polarities.

PMID- 10879398
TI  - Diagnosis of myocardial ischemia during ventricular pacing.
AB  - Discordant ST elevation > 5 mm was recently described as an electrocardiographic
      sign with good specificity and moderate sensitivity for the diagnosis of acute
      myocardial infarction during right ventricular pacing. This report shows that the
      same sign may occur transiently during myocardial ischemia and also serve as a
      diagnostic marker.

PMID- 10879399
TI  - Ventriculoatrial cross-talk dependent pacemaker syndrome.
AB  - A patient with dilated cardiomyopathy and DDD pacemaker experienced paroxysmal
      returns of her symptoms. IEGM revealed VA cross-talk resulting in functional
      undersensing of the following P wave that occurred during the PVARP and
      initiating a pacemaker syndrome with the pacemaker as a bystander.

PMID- 10879400
TI  - Survival of cats with naturally occurring chronic renal failure: effect of
      dietary management.
AB  - Fifty cats with naturally occurring stable chronic renal failure (CRF) were
      entered into a prospective study on the effect of feeding a veterinary diet
      restricted in phosphorus and protein with or without an intestinal phosphate
      binding agent on their survival from initial diagnosis. Twenty-nine cats accepted
      the veterinary diet, whereas compliance (due to limited intake by the cats or
      owner resistance to diet change) was not achieved in the remaining 21. At
      diagnosis, both groups of cats were matched in terms of age, bodyweight, plasma
      creatinine, phosphate, potassium and parathyroid hormone (PTH) concentrations,
      packed cell volume and urine specific gravity. Feeding the veterinary diet was
      associated with a reduction in plasma phosphate and urea concentrations and
      prevented the increase in plasma PTH concentrations seen in cats not receiving
      the diet. Cats fed the veterinary diet survived for longer when compared with
      those that were not (median survival times of 633 versus 264 days). These data
      suggest that feeding a diet specifically formulated to meet the needs of cats
      with CRF, together with phosphate binding drugs if required, controls
      hyperphosphataemia and secondary renal hyperparathyroidism, and is associated
      with an increased survival time.

PMID- 10879401
TI  - Idiopathic salivary gland enlargement (sialadenosis) in dogs: a microscopic
      study.
AB  - A histological, histochemical and morphometric study was performed on
      submandibular salivary glands from 13 dogs which had presented with a
      submandibular mass or swelling that proved to be a portion of non-inflammatory
      and non-neoplastic submandibular salivary gland. There were no consistent changes
      in lectin-binding histochemistry or immunohistochemical expression of various
      cell markers, and, in most cases, there was no measurable difference in acinar
      size in the affected gland. The possible explanation for the clinical salivary
      gland enlargement is therefore unclear.

PMID- 10879402
TI  - Diseases associated with pronounced eosinophilia: a study of 105 dogs in Sweden.
AB  - Records of 105 dogs with pronounced eosinophilia (>2.2 x 10(9) eosinophils/litre)
      were evaluated in a retrospective study to determine diseases associated with the
      abnormality in dogs in Sweden. Inflammatory disease in organs with large
      epithelial surfaces, such as the gut, lungs or skin, was found in 36 per cent of
      the dogs. A further one-quarter of the 105 cases were placed in the
      'miscellaneous' category, which comprised various diseases found at low
      frequency. The most well defined diagnosis was pulmonary infiltrates with
      eosinophils in 12 per cent of the dogs. A further 11 per cent had parasitic
      disease caused by either sarcoptic mange or nasal mite. No atopic dog was found
      and rottweilers were over-represented in most disease groups. Pronounced
      eosinophilia, in many cases transient, seems to be associated with a variety of
      disorders in dogs. In the present study, rottweilers appeared to be more prone to
      a high eosinophil response than other breeds.

PMID- 10879403
TI  - Collie eye anomaly in the rough collie in Sweden: genetic transmission and
      influence on offspring vitality.
AB  - Between 1989 and 1997, 8204 rough collies were examined for collie eye anomaly
      (CEA) at up to 10 weeks of age. All dogs were positively identified and the
      results were registered under the Swedish Kennel Club genetic health programme. A
      significant decrease in litter size occurred if one of two affected parents had
      coloboma (3.8 pups) compared with litters from two chorioretinal dysplasia- (CRD
      ) affected collies (5.2 pups) or litters by two normal collies (5.0 pups),
      indicating an influence of the coloboma genotype on offspring vitality. The
      prevalence of CRD in pups from normal x normal matings and CRD x CRD matings was
      significantly different from that expected under simple autosomal recessive
      inheritance (43 per cent versus 25 per cent and 85 per cent versus 100 per cent).
      The results are compatible with polygenic inheritance but not with simple
      autosomal recessive inheritance. CRD prevalence in offspring of CRD x coloboma
      matings was significantly lower than in pups of CRD x CRD matings, reflecting
      effects of the coloboma genotype on vitality. These results have important
      implications for breeding programmes and the genetic control of CEA.

PMID- 10879404
TI  - Ventral marsupialisation in the treatment of gastric dilatation-volvulus in two
      dogs.
AB  - A ventral marsupialisation technique is described which was used successfully to
      manage gastric dilatation-volvulus (GDV) in two large breed dogs. The procedure
      allowed the stomach to be completely and rapidly emptied and lavaged without
      peritoneal contamination. Drainage was maintained in the postoperative period for
      both dogs and the technique was expected to result in a permanent ventral
      gastropexy.

PMID- 10879405
TI  - Canine monocytic ehrlichiosis presenting as acute blindness 36 months after
      importation into the UK.
AB  - A four-year-old Labrador retriever developed sudden-onset blindness, associated
      with bilateral uveitis, intraocular haemorrhage and retinal detachment. It had
      been imported into the UK from Sardinia 36 months before presentation.
      Haematological abnormalities included non-regenerative anaemia, thrombocytopenia
      and neutropenia. Serum and urine protein electrophoresis demonstrated a
      monoclonal gammopathy. An immunofluorescent antibody test for Ehrlichia canis was
      positive, with a titre of 1:320, confirming a diagnosis of chronic monocytic
      ehrlichiosis. This case highlights how the prolonged subclinical phase of
      monocytic ehrlichiosis could enable infected dogs to enter the UK without signs
      of disease. Chronic monocytic ehrlichiosis should be considered in dogs which
      have been imported from E canis-endemic countries and present with bleeding
      disorders and gammopathy, even if signs develop many years after importation.

PMID- 10879406
TI  - Pemphigus foliaceus in association with systemic lupus erythematosus, and
      subsequent lymphoma in a cocker spaniel.
AB  - A seven-year-old neutered male cocker spaniel was presented with an 11-month
      history of generalised bacterial dermatitis. There were skin lesions over the
      entire body, which were round, slightly raised and encrusted. Skin biopsies were
      collected and the histological findings were consistent with pemphigus foliaceus.
      Immunohistochemical staining by the indirect immunoperoxidase method was
      positive, with desmosomal deposition of immunoglobulin (Ig) G. Haematological
      analysis revealed a regenerative anaemia and profound thrombocytopenia, while a
      Coombs' test was positive for polyvalent canine Coombs' reagent and anti-dog IgG.
      An antinuclear antibody test was positive, with a titre of 10,240. An ophthalmic
      examination demonstrated low tear production (keratoconjunctivitis sicca). Seven
      months after initial referral, the dog was re-presented with severe generalised
      peripheral lymphadenopathy. Radiographic evaluation of the thorax and abdomen
      revealed enlarged cranial mediastinal and sublumbar lymph nodes. Tru-Cut biopsy
      from an enlarged lymph node confirmed the diagnosis of lymphoma, which was
      phenotyped as a B-cell tumour. The diagnosis in this case was systemic lupus
      erythematosus, with the unusual feature of pemphigus foliaceus, and subsequent
      development of B-cell lymphoma. The case adds further to knowledge of the protean
      clinical presentations of canine autoimmune diseases and provides additional
      evidence for the potential association between autoimmunity and immune-system
      neoplasia in this species.

PMID- 10879408
TI  - Issues impacting on the small animal practitioner.

PMID- 10879407
TI  - Rabbit medicine-- gaining some know-how in the USA.

PMID- 10879409
TI  - How frequently should cats and dogs be vaccinated?

PMID- 10879410
TI  - Role of coronary calcification scanning in risk factor assessment.

PMID- 10879411
TI  - Pathophysiology of coronary calcification.
AB  - Calcification is a prominent feature of atherosclerosis, frequently associated
      with myocardial infarction and other adverse cardiovascular outcomes. Currently,
      calcification is widely viewed as an end-stage, degenerative process which is
      inevitable in advanced atherosclerosis. Pathologists, however, have long noted
      that calcification may occur early in atherosclerosis and, at times, may appear
      histologically identical to organized bone, including areas resembling bone
      marrow. These observations suggest that rather than being a passive process,
      atherosclerotic calcification may instead be an active, regulated process similar
      to that of osteogenesis. Using an in-vitro model of arterial calcification a
      subpopulation of artery wall cells, capable of producing hydroxyapatite mineral
      in vitro was discovered. This article discusses some of the cellular and
      molecular mechanisms of arterial calcification identified utilizing this in-vitro
      model of vascular calcification.

PMID- 10879412
TI  - Coronary calcification by electron beam tomography: comparison with coronary risk
      factors and angiography.
AB  - The development and progression of coronary artery disease is the result of
      exposure to a variety of different risk factors. In larger populations, strong
      associations exist between risk factors and the development of both angiographic
      and clinical coronary artery disease. But, this relationship is extremely
      variable in individual subjects. Coronary calcification is a specific marker of
      coronary artery disease. Its formation and progression is determined by largely
      identical risk factors compared with angiographic coronary artery disease.
      Coronary calcification quantitated by electron beam tomography (EBT) thus enables
      the non-invasive assessment of whether the risk factor exposure has actually led
      to the development of coronary atherosclerosis in an individual subject. Whereas
      other non-invasive tests focus on the physiological consequences of coronary
      obstruction, EBT represents anatomic disease itself. Because the propensity of
      plaques to cause coronary obstruction partly depends on the degree of arterial
      remodelling, large plaques may not necessarily appear as high-grade stenoses
      angiographically. Indeed, angiography and EBT evaluate two facets of
      atherosclerotic plaque disease, i.e. luminal obstruction and calcified plaque
      itself. Coronary calcification is strongly associated with the presence, extent,
      and severity of angiographic coronary artery disease. A number of studies have
      shown that it is clearly superior in this respect compared with conventional risk
      factors. However, because of the indirect relationships between plaque formation
      and luminal obstruction, EBT does not permit the site-specific prediction of
      coronary stenoses. Recent investigations have focused on the ability of EBT to
      represent the extent of anatomic coronary artery disease, which is an important
      predictor of future cardiac events. The availability of a simple, non-invasive
      test for the direct visualization of coronary artery disease holds great promise
      regarding improved definitions of the relationships between risk factors and
      coronary atherosclerosis as well as regarding the diagnosis of non-obstructive
      coronary disease, which can nevertheless result in acute events.

PMID- 10879413
TI  - Monitoring the effectiveness of preventive interventions using progression of
      coronary calcification with electron beam tomography.
AB  - Angiographic studies have demonstrated that progression of coronary artery
      disease can be slowed and in some cases regression obtained with appropriate
      medical therapies. However, coronary angiography is invasive and expensive.
      Detection of coronary artery calcification, a marker of atherosclerotic disease,
      with electron beam tomography imaging is achieved non-invasively and at a much
      lower cost. Therefore, this technology provides an opportunity to serially
      monitor the clinical effectiveness of medical therapy for coronary artery disease
      and could be useful for development of new therapies for atherosclerosis.

PMID- 10879414
TI  - Cost effectiveness of coronary calcification scanning using electron beam
      tomography in intermediate and high risk asymptomatic individuals.
AB  - Pharmaceutical therapy of hyperlipidemia is clearly beneficial. In the patient
      without established heart disease however, conventional risk assessment is
      imprecise and determining which patients are at highest versus lowest risk is a
      common clinical conundrum. It is well established that the most powerful
      determinant to risk is the overall extent/severity of coronary disease. Electron
      beam tomography (EBT) and quantification of coronary artery calcium has been
      shown to provide a valid non-invasive surrogate to atherosclerotic plaque burden.
      Screening patients who are considered to be at traditional intermediate to high
      risk by first using EBT can refine the broad-based population risk to a more
      individual basis. Data that is based upon a model developed for application of
      EBT are presented, which discuss its potential as a cost effective application to
      guide statin therapy in intermediate and high-risk sub-groups.

PMID- 10879415
TI  - Using coronary calcification scanning in the clinical practice of preventive
      cardiology.
AB  - Preventive therapies such as cholesterol reduction significantly reduce the risk
      of acute coronary events. Diagnostic tools that identify asymptomatic coronary
      atherosclerosis would permit initiation of aggressive preventive therapies at an
      earlier stage of coronary disease. Histologic and angiographic data demonstrate
      that coronary calcium has a very high sensitivity for the presence of coronary
      plaque. Therefore, coronary calcification can be regarded as a marker for
      coronary atherosclerosis. Coronary calcium scanning has been suggested as a tool
      for identification of a high-risk asymptomatic patient group. It can be utilized
      to guide the aggressiveness of risk factor modification and therapeutic
      preventive interventions toward those at higher risk for future events. Based on
      the available data, we review the clinical use of coronary calcium scanning in
      preventive cardiology.

PMID- 10879416
TI  - Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS):
      baseline characteristics and comparison with USA population.
AB  - BACKGROUND: Results of the Air Force/Texas Coronary Atherosclerosis Prevention
      Study (AFCAPS/TexCAPS) demonstrated that treatment with lovastatin, in addition
      to modifications of diet and lifestyle, reduced the rate of first acute major
      coronary events compared with placebo in a cohort that included participants with
      average to mildly elevated total levels of cholesterol, and below average levels
      of high-density lipoprotein cholesterol, women, and elderly subjects. OBJECTIVE:
      To describe the baseline characteristics of the study's cohort. DESIGN: This was
      a double-blind, placebo-controlled, primary-prevention trial in which Americans
      with average to mildly elevated total levels of cholesterol [4.65-6.83 mmol/l
      (180-264 mg/dl)] and no clinical evidence of atherosclerotic cardiovascular
      disease were randomly allocated either 20-40 mg/day lovastatin or placebo in
      addition to a low-saturated fat, low-cholesterol diet. Baseline characteristics
      of the study cohort are described, and the characteristics of a USA reference
      population based upon NHANES III data are provided for comparison. RESULTS: The
      study includes 5608 men (85%) and 997 women (15%) with mean total cholesterol
      level 5.71 +/- 0.54 mmol/l (221 +/- 21 mg/dl), low-density lipoprotein
      cholesterol level 3.88 +/- 0.44 mmol/l (150 +/- 17 mg/dl), high-density
      lipoprotein cholesterol 0.96 +/- 0.15 mmol/l (37 +/- 6 mg/dl), and median
      triglyceride level 1.78 +/- 0.86 mmol/l (158 +/- 76 mg/dl). The mean age is 58
      years (ranges 45-73 years for men and 55- 73 years for women). The participants
      are 89% white, 7% Hispanic, and 3% black. CONCLUSION: Results from AFCAPS/TexCAPS
      will be applicable to large segments of populations; in the USA alone, eight
      million share the demographic and baseline-lipid-level characteristics of the
      study cohort.

PMID- 10879417
TI  - How previous angina influences early prognosis of patients with acute myocardial
      infarction.
AB  - BACKGROUND: There is little information about how previous angina influences the
      complications of myocardial infarction and also contradictory results have been
      reported. OBJECTIVE: To compare the risk factors for myocardial infarction,
      complications, performance of left ventricle, and coronary angiography findings
      of patients who had suffered acute myocardial infarction with those for patients
      who had not. METHODS: We studied 600 patients diagnosed to have suffered acute
      myocardial infarction. Patients are grouped into those having previously had
      angina for at least 1 month preceding acute myocardial infarction (group I, n =
      308 patients; 223 men and 85 women, mean age 60.4 +/- 10.6 years) and those who
      had not had angina (group II, n = 292 patients; 221 men and 71 women, mean age 58
      +/- 9 years). The risk factors, complications (cardiogenic shock, heart failure,
      disturbances of rhythm and conduction, cardiac rupture and death), left-ventricle
      ejection fraction, and echocardiography and coronary angiographic findings during
      hospitalization are compared. RESULTS: There was no difference with respect to
      localization of myocardial infarction (anterior, inferior, and non-Q) between
      groups I and II (P> 0.05). Hypertension in members of group I was higher (P <
      0.05). There was no statistically significant difference with respect to diabetes
      mellitus, hypercholesterolemia and cigarette smoking (P > 0.05). Heart failure
      (P< 0.05), cardiogenic shock (P< 0.01), incidence of ventricular premature
      systole > 3/min (P< 0.001) and atrial fibrillation (P< 0.05) were seen more
      prevalently in group II than they were in group I. There was no difference
      between the two groups with respect to bundle-branch blockage and third-degree
      atrioventricular blockage. Incidences of ventricular fibrillation, rupture of
      interventricular septum (IVS) and death in hospital were higher in group II (6.2
      versus 3.6%, 6.2 versus 3.2%, 2.1 versus 0.6%) but were not statistically
      significant. Coronary angiography detected no statistically significant
      difference with respect to disease in left main coronary artery, and one-vessel
      and two-vessel disease; but three-vessel disease was significantly more prevalent
      in group II (P < 0.01). CONCLUSION: Heart failure, cardiogenic shock, arrhythmia
      (more than three VPS within 1 min and atrial fibrillation), and three-vessel
      disease detected by coronary angiography were found more often in the myocardial
      infarct patients without previous angina and these differences were statistically
      significant. In-hospital mortality and cardiac rupture were also found more
      commonly in this group and ejection fractions measured by echocardiography were
      found to be less, but these differences were statistically insignificant.

PMID- 10879418
TI  - Summer-winter differences in 24 h variability of heart rate.
AB  - OBJECTIVE: To examine possible seasonal changes in heart rate variability (HRV).
      BACKGROUND: Greater than normal mortality from cardiovascular disease (CVD) in
      the winter has been reported for many countries and might be partly explained by
      considering seasonal changes in CVD risk factors. Depression of HRV is an
      independent predictor of arrhythmic complications and of cardiac death, and it is
      also among the variables that may be affected by the season of the year. METHODS:
      We compared pairs of 24 h HRV data of 120 healthy men who were examined once in
      the summer and once in the winter. Multivariate analyses were performed for each
      dependent variable (HRV indexes) in separate statistical models with age, resting
      heart rate, serum level of cholesterol, cigarette smoking, body mass index,
      sports habits, alcohol consumption, systolic blood pressure, physical activity at
      work, years of education, consumption of energy, and season as the independent
      variables. RESULTS: Although there were no seasonal differences in mean R-R
      interval, all indexes of HRV were found to be lower in the summer than they were
      during winter. Differences and 95% confidence intervals were standard deviation
      (SD) of coupling intervals between normal beats 12 ms, 6-17 ms; SD of 5 min mean
      R-R intervals 14 ms, 8-20 ms; mean of all 5 min SD of R-R intervals 2.0 ms, 0.6
      2.5 ms; proportion of adjacent R-R intervals differing by > 50 ms 1.5%, 0.6-2.5%
      and root mean square of the difference between successive normal intervals 3.1
      ms, 1.5-4 ms. Multivariate analyses showed that HRV in the winter was less than
      that in the summer even after adjustment for age, serum level of cholesterol,
      systolic blood pressure, and body mass index. CONCLUSIONS: HRV indexes of healthy
      men vary physiologically by season, with lowest values obtained in the winter.
      Since low HRV is linked to pathologic conditions, the significance of seasonal
      changes for those suffering from CVD and their possible contribution to the
      greater mortality rates in winter have to be considered.

PMID- 10879419
TI  - Assessment of risk factors for coronary artery disease in divisions of internal
      medicine. The FAPOI Study Group. Federazione delle Associazioni dei Primari
      Ospedalieri Internisti.
AB  - OBJECTIVE: To determine the prevalences and clustering of risk factors for
      coronary artery disease among unselected patients admitted to the first level of
      hospitalization. METHODS: The survey was prospectively designed to review all the
      medical records of patients discharged in the week starting at 0800 h on 21
      October 1996. Family and personal histories of common risk factors, major routine
      biochemical data at entry, treatments during hospitalization and diagnoses at
      discharge (ICD-9 codes) were examined. In total 235 divisions of internal
      medicine uniformly distributed throughout Italy took part in the survey. RESULTS:
      The survey shows that unselected patients admitted to divisions of internal
      medicine are characterized by a high prevalence of risk factors for coronary
      artery disease. Some of these are incompletely assessed. Definition of the
      clustering of risk factors is also far from optimal. CONCLUSIONS: The risk
      profiles of unselected patients at cardiovascular risk hospitalized in divisions
      of internal medicine are incompletely assessed. Several reasons may prevent a
      thorough detection of risk factors and consequently their treatment. There is
      much potential for improvement.

PMID- 10879420
TI  - Bibliography. Current world literature.

PMID- 10879421
TI  - The effect of meteorological factors on the daily variation of airborne fungal
      spores in Granada (southern Spain).
AB  - A study was made of the link between climatic factors and the daily content of
      certain fungal spores in the atmosphere of the city of Granada in 1994. Sampling
      was carried out with a Burkard 7-day-recording spore trap. The spores analysed
      corresponded to the taxa Alternaria, Ustilago and Cladosporium, with two
      morphologically different spore types in the latter genus, cladosporioides and
      herbarum. These spores were selected both for their allergenic capacity and for
      the high level of their presence in the atmosphere, particularly during the
      spring and autumn. The spores of Cladosporium were the most abundant (93.82% of
      the total spores identified). The Spearman correlation coefficients between the
      spore concentrations studied and the meteorological parameters show different
      indices depending on the taxon being analysed. Alternaria and Cladosporium are
      significantly correlated with temperature and hours of sunlight, while Ustilago
      shows positive correlation indices with relative humidity and negative indices
      with wind speed.

PMID- 10879422
TI  - Meteorological phenomena affecting the presence of solid particles suspended in
      the air during winter.
AB  - Winter is not traditionally considered to be a risky season for people who suffer
      from pollen allergies. However, increasing numbers of people are showing symptoms
      in winter. This prompted our investigation into the levels of solid material in
      the air, and some of the meteorological phenomena that allow their accumulation.
      This study showed a possible relationship between the phenomenon of thermal
      inversion, which occurs when very low temperatures, cloudless skies and
      atmospheric calms coincide, and an increase in the concentration of solid
      material in the atmosphere. Frequently, this situation is associated with other
      predictable phenomena such as fog, dew and frost. This may allow a warning system
      to be derived for urban pollution episodes. The effect caused by parameters such
      as wind and rainfall was also analysed. Solid material was differentiated into
      non-biological material from natural and non-natural sources (e.g. soot, dust,
      sand, diesel exhaust particles, partially burnt residues) and biological
      material. The latter mainly comprises pollen grains and fungal spores. Owing to
      its abundance and importance as a causal agent of winter allergies, Cupressaceae
      pollen was considered separately.

PMID- 10879423
TI  - Development of a new instrument to measure oxygen saturation and total hemoglobin
      volume in local skin by near-infrared spectroscopy and its clinical application.
AB  - The oxygen saturation (StO2) and total hemoglobin volume in cutaneous blood are
      closely related to cutaneous metabolism and are important factors in determining
      the skin color. Most conventional apparatuses for the measurement of cutaneous
      metabolism have been designed to evaluate qualitative changes in the
      oxyhemoglobin volume, deoxyhemoglobin volume, and their sum (total Hb volume)
      relative to their baseline values. In this study, we developed an instrument for
      non-invasive evaluation of individual and regional differences in StO2 and Hb
      volume, a system unaffected by melanin (Kao PSA system model III), and examined
      the validity of its application. First, changes in StO2 and total Hb volume in
      the antebrachial region during venous occlusion and devascularization by
      compression of the brachial region were evaluated. Changes in total Hb volume
      following venous occlusion were found to reflect the cutaneous blood flow. Also,
      StO2 was considered to reflect the state of oxygen consumption by the skin,
      because it was markedly reduced during devascularization. Next, the subjects were
      exposed to graded hypobaric conditions, and the relationships among StO2,
      arterial blood oxygen saturation (SaO2), and venous blood oxygen saturation
      (SvO2) were studied. StO2 showed significant positive correlations with SaO2
      (r=0.811, P<0.001) and SvO2 (r=0.966, P<0.001), and its correlation with SvO2 was
      particularly strong. Therefore, StO2 was found to be closely dependent on SvO2.
      Lastly, StO2, total Hb volume, and other parameters were measured in healthy
      women (aged 20-69 years), and their regional differences and age-associated
      changes were evaluated. These regional differences (angle of mouth > cheek >
      forehead) and age-associated decreases in StO2 are considered to be caused by the
      age-associated decreases in the cutaneous blood flow.

PMID- 10879424
TI  - Effect of high altitude on sensitivity to the taste of phenylthiocarbamide.
AB  - Sensitivity to the taste of phenylthiocarbamide (PTC) was studied using the
      Harris-Kalmus method in healthy human volunteers at sea level and then
      subsequently at an altitude of 3500 m over a period of 3 weeks, after which they
      were brought back to sea level. Blood sugar, insulin and blood cortisol levels
      were estimated weekly. The results indicated that, out of 51 subjects studied, 26
      (55%) were PTC tasters at sea level. Eight of those unable to taste PTC at sea
      level tested as tasters at high altitude, and 2 of them reverted to being non
      tasters on return to sea level. In the blood, an increase in cortisol and blood
      insulin levels was seen without any significant change in sugar levels. All the
      changes recorded at high altitude tended to return to basal values after re
      induction to sea level. The study suggests that high-altitude hypoxia in some
      way, possibly involving changes in hormonal profile among other factors, causes
      an alteration in sensitivity to the taste of PTC, resulting in some of the
      individuals shifting to lower PTC sensitivity.

PMID- 10879425
TI  - The effect of "living high-training low" on physical performance in rats.
AB  - In this research, we hypothesized that, in rats, adaptation to high altitude
      (2500 m) plus training at low altitude (610 m), "living high-training low",
      improves physical performance at low altitude more than living and training at
      low altitude (610 m). Rats were divided into four groups: (1) living at low
      altitude (LL, n=12), (2) living and training at low altitude (LLTL, n=13), (3)
      living at high altitude (LH, n=12), (4) living at high altitude and training at
      low altitude (LHTL, n=13). The program for living at high altitude involved
      raising rats under hypobaric hypoxia (equivalent to 2500 m), and the training
      program consisted of running on a treadmill at low altitude. All groups were
      raised at each altitude and trained to run at 35 m/min for 40 min/day, 6
      days/week for 6 weeks. During this program, we measured heart rates both at rest
      and during exercise, and performed running-time trials. The mean heart rate
      during exercise was lower in groups with training than in groups without
      training, and the groups receiving training could run longer than the untrained
      groups. The LHTL group especially showed the lowest mean heart rate during
      exercise and the longest running time among all groups. After 6 weeks of the
      training program, all rats had a catheter implanted into the carotid artery, and
      the mean systemic arterial pressure was continuously measured during treadmill
      running. The rate of increase of this pressure as the running intensity increased
      was lower in groups with training than in groups without training, especially in
      the LHTL group. Finally, we anesthetized all the rats and extracted both the
      right and left ventricles, and the triceps surae and liver. Training increased
      the weight of the left ventricle, triceps surae, and liver. The increase in
      weight of the left ventricle and triceps surae was higher in the LHTL group than
      in the LLTL group in particular. It appeared that living high-training low may be
      an effective strategy to improve performance ability at low altitude.

PMID- 10879426
TI  - Thermoregulation in complex situations: combined heat exposure, infectious fever
      and water deprivation.
AB  - Heat exposure, infectious fever and water deprivation are stressors that,
      individually, produce disturbances in more than one regulated system, calling for
      diverse compensatory responses. A potential conflict is created when these
      stimuli are combined and impose concurrent stressful loads on the body because
      the homeostatic defenses mobilized against one are also partly needed against the
      other stressors. To learn how the competing demands of combined stressors for
      shared regulatory systems are met, rabbits were exposed to 32 degrees C and 37
      degrees C (heat), administered lipopolysaccharide (Salmonella enteritidis LPS, 2
      lg/kg, i.v.) in temperatures of 22 degrees C or 27 degrees C, or water-deprived
      for 1 or 2 days in 22 degrees C or 27 degrees C, in separate experiments. The
      corresponding controls were exposed to 22 degrees C or 27 degrees C, administered
      pyrogen-free saline i.v. in 22 degrees C or 27 degrees C, or normally hydrated in
      22 degrees C or 27 degrees C. In subsequent experiments, two or all three of
      these treatments were applied concurrently. Core and ear skin temperatures and
      respiratory rates were monitored continuously. The results indicated that the
      concomitant needs of moderate heat exposure, fever and 1 day of water deprivation
      were generally met by the regulatory systems involved, but different patterns of
      thermoeffector activities were evoked and the eventual body temperature changes
      produced were different under each condition. However, when the test conditions
      were severe, their combined needs were not met adequately and the eventual
      compensatory response depended not only on the particular stimulus intensity, but
      also on the immediate importance for survival of the functions being defended.
      Thus, dehydration was the most dangerous factor to the physiological integrity of
      the animals. In sum, conflicting physiological stimuli appear to result in
      responses that are different from the responses to a single perturbation, the
      eventual output representing the resultant of the inputs rather than a singular
      output dictated by one dominant drive to the exclusion of the others.

PMID- 10879427
TI  - Spatial and temporal variability of ground-level ozone in Castilla-Leon (Spain).
AB  - Ozone is a secondary air pollutant that has received extensive attention in the
      literature, mainly because of the adverse effects that exposure to it can cause,
      particularly in vegetation during the growing season. Because meteorological
      conditions strongly influence the efficiency of photochemical processes leading
      to ozone formation and destruction, ground-level ozone air pollution is currently
      being considered as a regional-scale phenomenon rather than a local one. This
      role of O3 as a regional-scale pollutant often implies the handling of large data
      sets in order to obtain information about its spatial and temporal variability
      patterns over a given broad region. Rotated principal component analysis (RPCA)
      is known to be one of the most powerful mathematical tools that can be used to
      achieve this aim. RPCA was applied in this paper to the summer and winter hourly
      time series of ground-level O3, concentrations recorded during 2 consecutive
      years (1996-1997) at 26 urban and suburban sites in Castilla-Leon (Spain). This
      procedure permitted the identification of different subregions where O3
      concentrations show different spatio-temporal variability patterns. These
      variability patterns are mainly associated with the interaction of regional-level
      meteorological and anthropogenic factors. Some differences between winter and
      summer patterns were also found.

PMID- 10879428
TI  - Emergent mechanisms in multiple pattern generation of the lobster pyloric
      network.
AB  - By using a hard-wired oscillator network, multiple pattern generation of the
      lobster pyloric network is simulated. The network model is constructed using a
      relaxation oscillator representing an oscillatory or quiescent (i.e. steady
      state) neuron. Modulatory inputs to the network are hypothesized to cause changes
      in the dynamical properties of each pyloric neuron: the oscillatory frequency,
      the postinhibitory rebound property, and the resting membrane potential. Changes
      in each of these properties are induced by changing appropriate parameters of the
      oscillator. By changing seven parameters of the network as a whole, modulatory
      input-dependent patterns are successfully simulated.

PMID- 10879429
TI  - Synchronization and sensitivity enhancement of the Hodgkin-Huxley neurons due to
      inhibitory inputs.
AB  - Recent experimental results imply that inhibitory postsynaptic potentials can
      play a functional role in realizing synchronization of neuronal firing in the
      brain. In order to examine the relation between inhibition and synchronous firing
      of neurons theoretically, we analyze possible effects of synchronization and
      sensitivity enhancement caused by inhibitory inputs to neurons with a
      biologically realistic model of the Hodgkin-Huxley equations. The result shows
      that, after an inhibitory spike, the firing probability of a single postsynaptic
      neuron exposed to random excitatory background activity oscillates with time. The
      oscillation of the firing probability can be related to synchronous firing of
      neurons receiving an inhibitory spike simultaneously. Further, we show that when
      an inhibitory spike input precedes an excitatory spike input, the presence of
      such preceding inhibition raises the firing probability peak of the neuron after
      the excitatory input. The result indicates that an inhibitory spike input can
      enhance the sensitivity of the postsynaptic neuron to the following excitatory
      spike input. Two neural network models based on these effects on postsynaptic
      neurons caused by inhibitory inputs are proposed to demonstrate possible
      mechanisms of detecting particular spatiotemporal spike patterns.

PMID- 10879430
TI  - Conditions for noise reduction and stable encoding of spatial structure by
      cortical neural networks.
AB  - Cortical circuits have been proposed to encode information by forming stable
      spatially structured attractors. Experimentally in the primary somatosensory
      cortex of the monkey, temporally invariant stimuli lead to spatially structured
      activity patterns. The purpose of this work is to study a recurrent cortical
      neural network model with lateral inhibition and examine what effect additive
      random noise has on the networks' ability to form stable spatially structured
      representations of the stimulus pattern. We show numerically that this network
      performs edge enhancement and forms statistically stationary, spatially
      structured responses when the lateral inhibition is of moderate strength. We then
      derive analytical conditions on the connectivity matrix that ensure stochasticly
      stable encoding of the stimulus spatial structure by the network. For stimuli
      whose strength falls in the near linear region of the sigmoid, we are able to
      give explicit conditions on the eigenvalues of the connection matrix. Finally, we
      prove that a network with a connection matrix, where the total excitation and
      inhibition impinging upon a neural unit are nearly balanced, will yield stable
      spatial attractor responses.

PMID- 10879431
TI  - Nonlinear analysis of continuous ECG during sleep I. Reconstruction.
AB  - In recent years evidence has accumulated that ECG signals are of a nonlinear
      nature. It has been recognized that strictly periodic cardiac rhythms are not
      accompanied by healthy conditions but, on the contrary, by pathological states.
      Therefore, the application of methods from nonlinear system theory for the
      analysis of ECG signals has gained increasing interest. Crucial for the
      application of nonlinear methods is the reconstruction (embedding) of the time
      series in a phase space with appropriate dimension. In this study continuous ECG
      signals of 12 healthy subjects recorded during different sleep stages were
      analysed. Proper embedding dimension was determined by application of two
      techniques the false nearest neighbours method and the saturation of the
      correlation dimension. Results for the ECG signals were compared with findings
      for simulated data (quasiperiodic dynamics, Lorenz data, white noise) and for
      phase randomized surrogates. Findings obtained with the two approaches suggest
      that embedding dimensions from 6 to 8 may be regarded as suitable for the
      topologically proper reconstruction of ECG signals.

PMID- 10879432
TI  - Nonlinear analysis of continuous ECG during sleep II. Dynamical measures.
AB  - The hypothesis that cardiac rhythms are associated with chaotic dynamics
      implicating a healthy flexibility has motivated the investigation of continuous
      ECG with methods of nonlinear system theory. Sleep is known to be associated with
      modulations of the sympathetic and parasympathetic control of cardiac dynamics.
      Thus, the differentiation of ECG signals recorded during different sleep stages
      can serve to determine the usefulness of nonlinear measures in discriminating ECG
      states in general. For this purpose the following six nonlinear measures were
      implemented: correlation dimension D2, Lyapunov exponent L1. Kolmogorov entropy
      K2, as well as three measures derived from the analysis of unstable periodic
      orbits. Results of this study show that continuous ECG signals can be
      differentiated from linear stochastic surrogates by each of the nonlinear
      measures. The most significant finding with respect to the sleep-related
      differentiation of ECG signals is an increase in dominant chaoticity assessed by
      L1 and a reduction in the degrees of freedom estimated by D2 during REM sleep
      compared to slow wave sleep. Our findings suggest that the increase in dominant
      chaoticity during REM sleep with regard to time-continuous nonlinear analysis is
      comparable to an increased heart rate variability. The reduction in the
      correlation dimension may be interpreted as an expression of the withdrawal of
      respiratory influences during REM sleep.

PMID- 10879433
TI  - Method for constructing the boundary of the bursting oscillations region in the
      neuron model.
AB  - We examine the problem of constructing the boundary of bursting oscillations on a
      parameter plane for the system of equations describing the electrical behaviour
      of the membrane neuron arising from the interaction of fast oscillations of the
      cytoplasma membrane potential and slow oscillations of the intracellular calcium
      concentration. As the boundary point on the parameter plane we consider the
      values at which the limit cycle of the slow subsystem is tangent to the Hopf
      bifurcation curve of the fast subsystem. The method suggested for determining the
      boundary is based on the dissection of the system variables into slow and fast.
      The strong point of the method is that it requires the integration of the slow
      subsystem only. An example of the application of the method for the
      stomatogastric neuron model [Guckenheimer J, Gueron S, Harris-Warrick RM (1993)
      Philos Trans R Soc Lond B 341: 345-359] is given.

PMID- 10879434
TI  - On the possibility of linear modelling the human arm neuromuscular apparatus.
AB  - It has been widely claimed that linear models of the neuromuscular apparatus give
      very inaccurate approximations of human arm reaching movements. The present paper
      examines this claim by quantifying the contributions of the various non-linear
      effects of muscle force generation on the accuracy of linear approximation. We
      performed computer simulations of a model of a two-joint arm with six
      monarticular and biarticular muscles. The global actions of individual muscles
      resulted in a linear dependence of the joint torques on the joint angles and
      angular velocities, despite the great nonlinearity of the muscle properties. The
      effect of time delay in force generation is much more important for model
      accuracy than all the non-linear effects, while ignoring this time delay in
      linear approximation results in large errors. Thus, the viscosity coefficients
      are rather underestimated and some of them can even be paradoxically estimated to
      be negative. Similarly, our computation showed that ignoring the time delay
      resulted in large errors in the estimation of the hand equilibrium trajectory.
      This could explain why experimentally estimated hand equilibrium trajectories may
      be complex, even during a simple reaching movement. The hand equilibrium
      trajectory estimated by a linear model becomes simple when the time delay is
      taken into account, and it is close to that actually used in the non-linear
      model. The results therefore provide a theoretical basis for estimating the hand
      equilibrium trajectory during arm reaching movements and hence for estimating the
      time course of the motor control signals associated with this trajectory, as set
      out in the equilibrium point hypothesis.

PMID- 10879435
TI  - Modeling observed chaotic oscillations in bursting neurons: the role of calcium
      dynamics and IP3.
AB  - Chaotic bursting has been recorded in synaptically isolated neurons of the
      pyloric central pattern generating (CPG) circuit in the lobster stomatogastric
      ganglion. Conductance-based models of pyloric neurons typically fail to reproduce
      the observed irregular behavior in either voltage time series or state-space
      trajectories. Recent suggestions of Chay [Biol Cybern 75: 419-431] indicate that
      chaotic bursting patterns can be generated by model neurons that couple membrane
      currents to the nonlinear dynamics of intracellular calcium storage and release.
      Accordingly, we have built a two-compartment model of a pyloric CPG neuron
      incorporating previously described membrane conductances together with
      intracellular Ca2+ dynamics involving the endoplasmic reticulum and the inositol
      1,4,5-trisphosphate receptor IP3R. As judged by qualitative inspection and
      quantitative, nonlinear analysis, the irregular voltage oscillations of the model
      neuron resemble those seen in the biological neurons. Chaotic bursting arises
      from the interaction of fast membrane voltage dynamics with slower intracellular
      Ca2+ dynamics and, hence, depends on the concentration of IP3. Despite the
      presence of 12 independent dynamical variables, the model neuron bursts
      chaotically in a subspace characterized by 3-4 active degrees of freedom. The
      critical aspect of this model is that chaotic oscillations arise when membrane
      voltage processes are coupled to another slow dynamic. Here we suggest this slow
      dynamic to be intracellular Ca2+ handling.

PMID- 10879436
TI  - Arterial pulse wave velocity and risk factors for peripheral vascular disease.
AB  - Non-invasive measurement of arterial pulse wave velocity (PWV) is used to
      diagnose peripheral vascular disease. We examined the relationship between PWV
      and risk factors related to peripheral vascular disease [body mass index (BMI),
      systolic blood pressure (SBP), diastolic blood pressure (DBP), serum total
      cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), atherogenic index
      (AI) and blood glucose (GLU)] in 45 healthy male volunteers, aged 25-85 years.
      The correlation coefficient of PWV with age was r = 0.46, and the correlation
      coefficients of PWV with DBP, AI and GLU were r = 0.71, 0.56, and 0.22,
      respectively (P < 0.05). Multiple linear regression analysis revealed that 67% of
      the variance in PWV could be accounted for by these three variables. The relative
      contributions of DBP, AI and GLU to PWV were 66%, 26% and 8%, respectively. To
      test the applicability of PWV for clinical use, a multiple regression equation of
      PWV derived from these three variables was then applied to male patients with
      hypertension (n = 53), hyperlipidaemia (n = 35) or hyperglycaemia (n = 39). The
      results suggest that the multiple regression equation of PWV is an indicator that
      discriminates between these patient categories and healthy men.

PMID- 10879437
TI  - Heart rate variability during dynamic exercise in elderly males and females.
AB  - It has been proposed that cardiac control is altered in the elderly. Power
      spectral analysis of heart rate variability (HRV) was performed on 12 male and 11
      female elderly subjects (mean age 74 years) while at rest in supine and sitting
      positions, and at steady states during 5 min of exercise (35-95% peak oxygen
      consumption, VO2peak). There were no differences in power, measured as a
      percentage of the total of the high frequency peak (HF, centred at about 0.25 Hz;
      13% in males vs 12% in females), low frequency peak (LF, centred at 0.09 Hz; 25%
      in males and 22% in females), and very low frequency component (VLF, at 0.03 Hz;
      66% in males and 69% in females) between body positions at rest. There was no
      difference in spectral power between male and female subjects. Total power
      decreased as a function of oxygen consumption during exercise, LF% did not change
      up to about 14 ml x kg(-1) x min(-1) (40% and 80% VO2peak in males and females,
      respectively), then decreased towards minimal values in both genders. HF% power
      and central frequency increased linearly with metabolic demand, reaching higher
      values in male subjects than in female subjects at VO2peak, while VLF% remained
      unchanged. Thus, the power spectra components of HRV did not reflect the changes
      in autonomic activity that occur at increasing exercise intensities, confirming
      previous findings in young subjects, and indicated similar responses in both
      genders.

PMID- 10879438
TI  - Gender differences in body fat of low- and high-body-mass children: relationship
      with body mass index.
AB  - The primary objective of this study was to determine gender differences in total
      body fat mass (TBFM) and body fat distribution (subcutaneous fat mass, SFM; and
      internal fat mass, IFM) in a cross-sectional sample of 280 children. Measurements
      of the body composition of 141 boys and 139 girls, all apparently healthy and
      aged 3-6 years were made using bioelectrical impedance. Determinations of
      impedance were made using a four-terminal impedance analyzer (TP-95K; Toyo
      Physical, Fukuoka, Japan). Lean body mass (LBM) was calculated using a previously
      published equation [Goran MI, Kaskoun MC, Carpenter WH, Poehlman ET, Ravussin E,
      Fontvieikke A-M (1993) Estimating body composition of young children by using
      bioelectrical resistance. J Appl Physiol 75: 1776-1780]. SFM was calculated using
      a modification of the equation derived by Skerjl [Skerjl B, Brozek J, Hunt EE
      (1953) Subcutaneous fat and age changes in body build and body form in women. Am
      J Phys Anthrop 11: 577-580] and Davies [Davies PSW, Jones PRM, Norgan NG (1986)
      The distribution of subcutaneous and internal fat in man. Ann Hum Biol 13: 189
      192]. The main modifications of the equation in the present study were the
      introduction of: (1) mean thickness of adipose tissue over body surface/2, and
      (2) skin mass. IFM was calculated as the difference between TBFM and SFM. The
      body mass index (BMI; kg/m2) was calculated from the formula: body mass/height2.
      For each gender, the subjects in the lowest and highest 25th percentiles were
      designated as "low body mass" and "high body mass", respectively. In the present
      study, no gender differences in absolute TBFM, SFM and IFM were observed in
      either of these groups. In contrast, gender differences in relative TBFM (%Fat)
      and SFM (SFM/mass) were evident in girls. However, the four subgroups were
      similar in terms of relative IFM (IFM/mass). The TBFM was independently related
      to SFM, IFM and %Fat in both genders after adjustment for BMI; however, there was
      no significant association of SFM with IFM after adjustment for BMI in any group.
      Even after adjustment for BMI, IFM was independently related to %Fat in both
      genders, although SFM was not independently related to %Fat in any group except
      low-body-mass boys. This study shows that relative TBFM and SFM are higher in
      high-body-mass groups and tend to be higher in girls than in boys, and that the
      higher %Fat in high-body-mass girls than in high-body-mass boys appears to be
      associated with internal adipose tissue deposits. External adipose tissue mass
      does not appear to be related to the higher %Fat levels in high-body-mass girls.
      In addition, subcutaneous fat mass appears to be higher in low-body-mass girls
      than in low-body-mass boys, although this observation needs confirmation using
      more valid measures of subcutaneous fat such as computerized tomography and
      magnetic resonance imaging.

PMID- 10879439
TI  - Factors limiting cold-water swimming distance while wearing personal floatation
      devices.
AB  - The influence of body adiposity, arm skinfold thickness, aerobic capacity, and
      cooling rate were studied in a mock survival swimming situation conducted in
      water at around 14 degrees C. Seventeen adult participants wore personal
      floatation devices on top of seasonal clothing and were asked to swim as far as
      they could, as if attempting to reach shore following an accidental immersion in
      cold water. Triceps and patellar skinfold thickness showed a significant
      correlation with distance covered (r = 0.70 and 0.56, respectively), while
      abdominal skinfold and percent body fat showed no significant correlation.
      Maximum oxygen consumption (VO2max) was not significantly related to distance
      covered. There was a negative correlation between body cooling rate during the
      swimming period and distance covered. A multiple stepwise regression analysis,
      however, indicated that the only significant contributor to variance in the
      distance covered was the triceps skinfold thickness (r2 = 0.49). It was concluded
      that for a healthy subject accidentally immersed in cold water, triceps skinfold
      thickness is a stronger predictor of the swimming distance covered than body
      adiposity, VO2max, or the drop in core temperature.

PMID- 10879440
TI  - Leg-press resistance training during 20 days of 6 degrees head-down-tilt bed rest
      prevents muscle deconditioning.
AB  - The purpose of this study was to investigate the effects of resistance training
      on the morphological and functional properties of human lower limb muscles during
      20 days of 6 degrees head-down-tilt bed rest. Nine men were randomly assigned to
      the resistance training group (BR-Tr, n = 5) or the non-training, control group
      (BR-Cont, n = 4). Isometric leg-press exercises were performed: 3 s x 30
      repetitions (30 s rest between repetitions) daily for 20 days during the bed-rest
      period. Serial axial magnetic resonance images were taken from the right thigh
      and leg muscles, and muscle volume, muscle length, and fibre length were
      estimated. The physiological cross-sectional areas (PCSAs) of the knee extensor,
      knee flexor, ankle plantarflexor, and ankle dorsiflexor (tibialis anterior)
      muscle groups were determined as muscle volume multiplied by the cosine of the
      angle of fibre pennation divided by fibre length. Maximum voluntary contraction
      (MVC) during knee extension was measured. No significant changes were observed in
      the PCSA of the knee extensor muscles in BR-Tr group, whereas the PCSA in the BR
      Cont group decreased by 7.8%. The PCSA of the knee flexor and plantarflexor
      muscles in the BR-Tr group and BR-Cont group significantly decreased after bed
      rest (knee flexors, 10.2% and 11.5%; plantarflexors, 13.0% and 12.8%,
      respectively). However, in both groups bed rest had no effect on the muscle
      volume and PCSA of the tibialis anterior. MVC was maintained by resistance
      training in the BR-Tr group (decreased by 1%). In contrast, a decline of strength
      was observed in the BR-Cont group (-16%), but this result was not statistically
      significant. These results suggest that isometric leg-press training prevents the
      deconditioning (i.e. atrophy and decline of strength) of the knee extensor muscle
      group.

PMID- 10879441
TI  - Response of the human triceps surae muscle to electrical stimulation during
      varying levels of blood flow restriction.
AB  - The changes in muscle force associated with varying degrees of lower-limb
      ischaemia were investigated. Isometric torque production by the triceps surae
      muscle was measured during a 5-min continuous train of 2-Hz electrical
      stimulation in six healthy young adults under different thigh cuff occlusion
      pressures. The reproducibility of this protocol when performed under complete
      ischaemia (tested five times over a 2-week period) was assessed as having a
      coefficient of variation (CV) for fatigue (end/initial force) of [mean (SEM) 12
      (1)%; n = 5]. This compares favourably with that obtained for maximum voluntary
      contraction torque [CV 9 (1)%]. In six subjects, triceps surae muscle fatigue was
      assessed under thigh cuff pressures of 0, 6.7 kPa (50 mmHg, venous occlusion) and
      28 kPa (210 mmHg, complete ischaemia), as well as two intermediate levels of
      occlusion that were established by cuff pressures of 13.4 (0.5) and 20.3 (1.1)
      kPa [103 (4) and 152 (8) mmHg, respectively]. These corresponded to ankle
      brachial pressure indices of 1.3 and 0.8, respectively when subjects were seated,
      or 0.8 and 0.36 when supine. With undisturbed lower-leg circulation, force
      potentiated steadily over the 5 min of stimulation such that the final force was
      135 (8)% of the initial value. With complete ischaemia, force fell to 47 (2)% of
      the initial value. Stimulation under thigh occlusion pressures of 6.7, 13.4 and
      20.3 kPa elicited intermediate levels of reduction in force, graded according to
      the increasing restriction of perfusion. The results show that low-force twitch
      contractions, which themselves do not occlude blood flow, are extremely sensitive
      to impaired perfusion and may represent a viable alternative to established
      methods of muscle performance assessment in patients with blood flow
      insufficiency.

PMID- 10879442
TI  - The effect of endurance training on the ventilatory response to exercise in elite
      cyclists.
AB  - The purpose of this study was to investigate the effects of endurance training on
      the ventilatory response to acute incremental exercise in elite cyclists. Fifteen
      male elite cyclists [mean (SD) age 24.3 (3.3) years, height 179 (6) cm, body mass
      71.1 (7.6) kg, maximal oxygen consumption (VO2max) 69 (7) ml x min(-1) x kg(-1)]
      underwent two exercise tests on a cycle ergometer. The first test was assessed in
      December, 6 weeks before the beginning of the cycling season. The second test was
      performed in June, in the middle of the season. During this period the subjects
      were expected to be in a highly endurance-trained state. The ventilatory response
      was assessed during an incremental exercise test (20 W x min(-1)). Oxygen
      consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), and
      heart rate (HR) were assessed at the following points during the test: at
      workloads of 200 W, 250 W, 300 W, 350 W, 400 W and at the subject's maximal
      workload, at a respiratory exchange ratio (R) of 1, and at the ventilatory
      threshold (Th(vent)) determined using the V-slope-method. Post-training, the mean
      (SD) VO2max was increased from the pre-training level of 69 (7) ml x min(-1) x
      kg(-1) (range 61.4-78.6) to 78 (6) ml x min(-1) x kg(-1) (range 70.5-86.3). The
      mean post-training VO2 was significantly higher than the pre training value (P <
      0.01) at all work rates, at Th(vent) and at R = 1. VO2 was also higher at all
      work rates except for 200 W and 250 W. VE was significantly higher at Th(vent)
      and R = 1. Training had no effect on HR at all workloads examined. An explanation
      for the higher VO2 cost for the same work rate may be that in the endurance
      trained state, the adaptation to an exercise stimulus with higher intensity is
      faster than for the less-trained state. Another explanation may be that at the
      same work rate, in the less-endurance-trained state power is generated using a
      significantly higher anaerobic input. The results of this study suggest the
      following practical recommendations for training management in elite cyclists:
      (1) the VO2 for a subject at the same work rate may be an indicator of the
      endurance-trained state (i.e., the higher the VO2, the higher the endurance
      trained capacity), and (2) the need for multiple exercise tests for determining
      the HR at Th(vent) during a cycling season is doubtful since at Th(vent) this
      parameter does not differ much following endurance training.

PMID- 10879443
TI  - Prediction of the average skin temperature in warm and hot environments.
AB  - The prediction of the mean skin temperature used for the Required Sweat Rate
      index was criticised for not being valid in conditions with high radiation and
      high humidity. Based on a large database provided by 9 institutes, 1999 data
      points obtained using steady-state conditions, from 1399 experiments and
      involving 377 male subjects, were used for the development of a new prediction
      model. The observed mean skin temperatures ranged from 30.7 degrees C to 38.6
      degrees C. Experimental conditions included air temperatures (Ta) between 20 and
      55 degrees C, mean radiant temperatures (Tr) up to 145 degrees C, partial vapour
      pressures (Pa) from 0.2 to 5.3 kPa, air velocities (v(a)) between 0.1 and 2 m/s,
      and metabolic rates (M) from 102 to 620 W. Rectal temperature (T(re)) was
      included in the models to increase the accuracy of prediction. Separate models
      were derived for nude (clothing insulation, I(cl), < or = 0.2 clo, where 1 clo =
      0.155 m2 x degrees C x W(-1), which is equivalent to the thermal insulation of
      clothing necessary to maintain a resting subject in comfort in a normally
      ventilated room, air movement = 10 cm/s, at a temperature of 21 degrees C and a
      humidity of less than 50%) and clothed (0.6 < or = I(cl) < or = 1.0 clo) subjects
      using a multiple linear regression technique with re-sampling (non-parametric
      bootstrap). The following expressions were obtained for nude and clothed
      subjects, respectively: T(sk) = 7.19 + 0.064Ta + 0.061Tr + 0.198Pa - 0.348v(a) +
      0.616T(re) and T(sk) = 12.17 + 0.020Ta + 0.044Tr + 0.194Pa - 0.253v(a) + 0.0029M
      + 0.513T(re). For the nude and clothed subjects, 83.3% and 81.8%, respectively,
      of the predicted skin temperatures were within the range of +/- 1 degree C of the
      observed skin temperatures. It is concluded that the proposed models for the
      prediction of the mean skin temperature are valid for a wide range of warm and
      hot ambient conditions in steady-state conditions, including those of high
      radiation and high humidity.

PMID- 10879444
TI  - Cytokines and cell adhesion molecules associated with high-intensity eccentric
      exercise.
AB  - Unaccustomed, eccentrically biased exercise induces trauma to muscle and/or
      connective tissue. Tissue damage activates an acute inflammatory response.
      Inflammation requires the effective interaction of different physiological and
      biological systems. Much of this is coordinated by the de novo synthesis of
      families of protein molecules, cytokines. The purpose of the present paper was to
      determine changes in blood levels of various cytokines in response to exercise
      induced muscle damage that was effected using high-intensity eccentric exercise.
      Six healthy, untrained, college-age male subjects were required to perform the
      eccentric phase of a bench press and a leg curl (4 sets, 12 repetitions/set) at
      an intensity equivalent to 100% of their previously determined one-repetition
      maximum. Samples of blood were drawn at the following times: before exercise and
      1.5, 6, 12, 24, 48, 72, 96, 120, and 144 h after exercise. These samples were
      analyzed for interleukins (IL): IL-1beta, IL-6, and IL-10; tumor necrosis factor
      alpha; colony stimulating factors (CSF): granulocyte-CSF, macrophage-CSF, and GM
      CSF; for cell adhesion molecules (CAM): P- and E-selectin, and intercellular cell
      adhesion molecule (ICAM-1), and vascular cell adhesion molecule (VCAM-1). Results
      were analyzed using a repeated-measures analysis of variance (P = 0.05). Compared
      to baseline values, IL-1beta was reduced (P = 0.03) at 6, 24, and 96-144 h after
      exercise; IL-6 was elevated (P = 0.01) at 12, 24, and 72 h after exercise; IL-10
      was elevated (P = 0.009) between 72 and 144 h after exercise; M-CSF was elevated
      (P = 0.005) at 12 and 48-144 h after exercise; and P-selectin was reduced (P =
      0.01) between 24 and 144 h after exercise. It is concluded that when high
      intensity eccentric exercise is compared to strenuous endurance exercise, post
      exercise changes in cytokines do occur, but they are generally of a smaller
      magnitude, and occur at a later time period after the termination of exercise.

PMID- 10879445
TI  - Plasma catecholamine responses and neural adaptation during short-term resistance
      training.
AB  - Low exercise-induced plasma adrenaline (A) responses have been reported in
      resistance-trained individuals. In the study reported here, we investigated the
      interaction between strength gain and neural adaptation of the muscles, and the
      plasma A response in eight healthy men during a short-term resistance-training
      period. The subjects performed 5 resistance exercises (E1-E5), consisting of 6
      sets of 12 bilateral leg extensions performed at a 50% load, and with 2 days rest
      in between. Average electromyographic (EMG) signal amplitude was recorded before
      and after the exercises, from the knee extensor muscles in isometric maximal
      voluntary contraction (MVC) as well as during the exercises (aEMGmax and
      aEMGexerc, respectively). Total oxygen consumed during the exercises (VO2tot) was
      also measured. All of the exercises were exhaustive and caused significant
      decreases in MVC (34-36%, P < 0.001). As expected, the concentric one-repetition
      maximum (1-RM), MVC and aEMGmax were all higher before the last exercise (E5)
      than before the first exercise (E1; 7, 9 and 19%, respectively, P < 0.05). In
      addition, in E5 the aEMGexerc:load and VO2tot:load ratios were lower than in E1 (
      5 and -14%, P < 0.05), indicating enhanced efficiency of the muscle contractions,
      However, the post-exercise plasma noradrenaline (NA) and A were not different in
      these two exercises [mean (SD) 10.2 (3.8) nmol x l(-1) vs 11.3 (6.0) nmol x l(
      1), ns, and 1.2 (1.0) nmol x l(-1) vs 1.9 (1.1) nmol x l(-1), ns, respectively].
      However, although NA increased similarly in every exercise (P < 0.01), the
      increase in A reached the level of statistical significance only in E1 (P <
      0.05). The post-exercise A was also already lower in E2 [0.7 (0.7) nmol x l(-1),
      P < 0.05) than in E1, despite the higher post-exercise blood lactate
      concentration than in the other exercises [9.4 (1.1) mmol x l(-1), P < 0.05].
      Thus, the results suggest that the observed attenuation in the A response can not
      be explained by reduced exercise-induced strain due to the strength gain and
      neural adaptation of the muscles. Correlation analysis actually revealed that
      those individuals who had the highest strength gain during the training period
      even tended to have an increased post-exercise A concentration in the last
      exercise as compared to first one (r = 0.76, P < 0.05).

PMID- 10879446
TI  - Relationship between muscle T2* relaxation properties and metabolic state: a
      combined localized 31P-spectroscopy and 1H-imaging study.
AB  - A multi-volume 31P-magnetic resonance spectroscopy localization procedure was
      implemented to compare directly muscle metabolism and proton T2* relaxation
      properties in the human plantar flexor muscles during exercise. Localized 31P
      spectra were collected simultaneously from the medial gastrocnemius, lateral
      gastrocnemius and soleus muscles during exercise using beta1-insensitive Hadamard
      Spectroscopic Imaging (HSI). 1H T2*-weighted gradient-echo images were acquired
      at rest and immediately following high-intensity plantar flexion exercise. T2*
      mapping of the individual calf muscles showed that plantar flexion with the knee
      extended produces significant increases (P < 0.0001) in the mean (SEM) T2* of the
      medial [35.6 (1.2) ms vs 28.5 (0.5) ms at rest] and lateral gastrocnemius [35.6
      (0.9) ms vs 26.2 (0.9) ms at rest], but not in the soleus [26.7 (0.6) ms vs 27.3
      (0.8) ms at rest]. In accordance with the changes in T2*, the ratio of inorganic
      phosphate to phosphocreatine (Pi:PCr) and the intracellular muscle pH shifted
      significantly in the gastrocnemii, while the soleus showed no change in muscle pH
      and only a moderate increase in Pi-to-Ph. Comparison of spectroscopic and
      relaxation parameters in both gastrocnemius muscles revealed a significant
      relationship between post-exercise T2* and intracellular pH (r = 0.72-0.76) and
      Pi-to-Ph ratios (r = 0.81-0.88) during exercise. Using an improved method of
      localization, this study confirms the existence of a strong relationship between
      transverse relaxation properties and the metabolic state in skeletal muscles
      engaged in heavy exercise.

PMID- 10879447
TI  - Leg extensor power and dehydroepiandrosterone sulfate, insulin-like growth factor
      I and testosterone in healthy active elderly people.
AB  - We examined the association between quadriceps muscle function and serum levels
      of dehydroepiandrosterone sulphate (DHEAS), insulin-like growth factor I (IGF-I)
      and testosterone in a group of healthy elderly people. Fifty-three independent,
      community-dwelling elderly subjects (26 men and 27 women) aged from 66 to 84
      years volunteered to participate in the study. Physical activity (PA) was
      evaluated by a questionnaire. Quadriceps maximal muscle power (Wmax) and optimal
      shortening velocity (v(opt)) were measured on a friction-loaded non-isokinetic
      cycle ergometer. The Wmax is expressed in relation to body mass (W(max/kg), W x
      kg(-1)), and in relation to the mass of the two quadriceps muscles (W(max/Quadr),
      W x kg(Quadr(-1))). In women, when adjusted for age, anthropometric measurements
      and PA indices, IGF-I correlated significantly with W(max/kg) (partial
      correlation: r = 0.59; P = 0.001), W(max/Quadr) (r = 0.58; P = 0.002) and v(opt)
      (r = 0.53; P = 0.004), whereas DHEAS was correlated significantly with W(max/kg)
      (r = 0.54; P = 0.003) and W(max/Quadr) (r = 0.58; P = 0.002). No such correlation
      was found in men. These findings indicate that in healthy elderly women lower
      values for quadriceps muscle Wmax and v(opt) are related, independently of age,
      anthropometric measurements and PA indices, to lower circulating levels of DHEAS
      and IGF-I.

PMID- 10879448
TI  - Physiological predictors of flat-water kayak performance in women.
AB  - This study was conducted to investigate the relationship between selected
      physiological variables and 500-m flat-water kayak (K500) performance. Nine
      female, high-performance kayak paddlers, mean (SD) age 23 (5) years, participated
      in this investigation. Testing was conducted over 6 days and included
      anthropometric measurements (height, body mass and skinfolds), an incremental
      test to determine both peak VO2 and the "anaerobic threshold" (Th(an)), and a 2
      min, all-out test to calculate accumulated oxygen deficit (AOD). Blood lactate
      concentrations were measured during the incremental test and at the completion of
      both tests. Subjects also completed a K500 race under competition conditions.
      K500 time was significantly correlated with both peak VO2 (r = -0.82, P < 0.05)
      and the power output achieved at the end of the incremental test (r = -0.75, P <
      0.05). However, the variable most strongly correlated with K500 time was Th(an)
      (r = -0.89, P < 0.05). A stepwise multiple regression, for which r = 0.95 and the
      standard error of estimate = 1.6 s, yielded the following equation: K500time(s) =
      160.6-0.154 x AOD x kg(-1) - 0.250 x Th(an). In conclusion, the results of this
      study have demonstrated that although K500 performance is a predominantly aerobic
      activity, it does require a large anaerobic contribution. The importance of both
      the aerobic and anaerobic energy systems is reflected by the K500 time being best
      predicted by a linear combination of Th(an) and AOD x kg(-1). This suggests the
      need to develop and implement training programmes that develop optimally both of
      these physiological attributes. Further research is required to elucidate the
      most effective means by which to develop both the aerobic and anaerobic energy
      systems.

PMID- 10879449
TI  - Training and natural immunity: effects of diets rich in fat or carbohydrate.
AB  - The purpose of the study was to investigate whether a carbohydrate-rich versus
      fat-rich diet influenced the effect of training on the immune system. Ten
      untrained young men ingested a carbohydrate-rich diet [65 energy percent (E%)
      carbohydrate] and ten subjects a fat-rich diet (62E% fat) while endurance
      training was performed 3-4 times a week for 7 weeks. Maximal oxygen uptake
      increased by 11% in both groups. Blood samples for immune monitoring were
      collected before and at the end of the study. Blood samples were also collected,
      in parallel, from 20 age-matched subjects, and data from these subjects were used
      to eliminate day-to-day variation in the immunological tests. Independently of
      diet, training increased the percentage of CD3-CD16+ CD56+ natural killer (NK)
      cells from [mean (SEM)] 14 (1) % to 20 (3) % (P = 0.05), whereas the NK-cell
      activity, either unstimulated or stimulated with interleukin (IL)-2 or interferon
      (IFN)-alpha, did not change. Furthermore, training did not influence the
      percentages of CD3+, CD4+, CD8+, CD19+ or CD14+ cells. However, when the two diet
      groups were compared, it was found that the NK-cell activity had increased in the
      group on the carbohydrate-rich diet [from 16 (3)% to 27 (2)%] and decreased in
      the group on the fat-rich diet [from 26 (2)% to 20 (4)%] in response to training.
      The effect of training on unstimulated NK-cell activity was significantly
      different between the groups (P = 0.007). These data indicate that diet
      manipulation during training may influence natural immunity, and suggest that
      ingestion of a fat-rich diet during training is detrimental to the immune system
      compared to the effect of a carbohydrate-rich diet.

PMID- 10879450
TI  - Augmentation of blood circulation to the fingers by warming distant body areas.
AB  - Future activities in space will require greater periods of time in extreme
      environments in which the body periphery will be vulnerable to chilling.
      Maintaining the hands and fingers in comfortable conditions enhances finger
      flexibility and dexterity, and thus effects better work performance. We have
      evaluated the efficacy of promoting heat transfer and release by the extremities
      by increasing the blood flow to the periphery from more distant parts of the
      body. The experimental garment paradigm developed by the investigators was used
      to manipulate the temperature of different body areas. Six subjects, two females
      and four males, were evaluated in a stage-1 baseline condition, with the inlet
      temperature of the circulating water in the liquid cooling/warming garment (LCWG)
      at 33 degrees C. At stage 2 the total LCWG water inlet temperature was cooled to
      8 degrees C, and at stage 3 the inlet water temperature in specific segments of
      the LCWG was warmed (according to protocol) to 45 degrees C, while the inlet
      temperature in the rest of the LCWG was maintained at 8 degrees C. The following
      four body-area-warming conditions were studied in separate sessions: (1) head,
      (2) upper torso/arm, (3) upper torso/arm/head, and (4) legs/feet. Skin
      temperature, heat flux and blood perfusion of the fingers, and subjective
      perception of thermal sensations and overall physical comfort were assessed.
      Finger temperature (T(fing)) analyses showed a statistically significant
      condition x stage interaction. Post-hoc comparisons (T(fing)) indicated that at
      stage 3, the upper torso/arm/head warming condition was significantly different
      from the head, upper torso/arm and legs/feet conditions, showing an increase in
      T(fing). There was a significant increase in blood perfusion in the fingers at
      stage 3 in all conditions. Subjective perception of hand warmth, and overall
      physical comfort level significantly increased in the stage 3 upper
      torso/arm/head condition. The findings indicate that physiological methods to
      enhance heat transfer by the blood to the periphery within protective clothing
      provide an additional tool for increasing total and local human comfort in
      extreme environments.

PMID- 10879451
TI  - Evaluation of the Lactate Pro blood lactate analyser.
AB  - An evaluation of the hand-held portable Lactate Pro Analyser (KDK) was undertaken
      to assess its accuracy, reliability and versatility. Capillary blood samples were
      drawn from elite athletes in both laboratory and field settings and analysed in
      parallel. Accuracy was determined in relation to three other lactate analysers:
      (1) the ABL 700 Series Acid-Base analyser (n = 172 cases), (2) the Accusport
      Lactate Meter (n = 118 cases), and (3) the YSI 2300 Stat lactate analyser (n = 22
      cases). The level of agreement was determined over the range of 1-18 mM. The
      repeatability of results between two different Lactate Pro analysers was also
      determined over the same range. Versatility was assessed in the field, where the
      Lactate Pro was used with elite athletes under a range of outdoor and indoor
      testing conditions. The correlations between the Lactate Pro and the ABL 700
      Series Acid-Base analyser, YSI 2300 and Accusport were r = 0.98, r = 0.99, r =
      0.97. The correlation between the two Lactate Pro analysers on the same sample (n
      = 96 cases) was r = 0.99. The level of agreement between the Lactate Pro and
      other analysers was generally less than +/- 2.0 mM over the physiological range
      of 1.0-18.0 mM (range of mean difference: -0.06 mM to 0.52 mM). The Lactate Pro
      was easy to operate and successfully completed the sample analysis in 100% of the
      tests performed. In summary, the Lactate Pro is accurate, reliable and exhibits a
      high degree of agreement with other lactate analysers.

PMID- 10879452
TI  - Genetic variation in the renin-angiotensin system and athletic performance.
AB  - The D allele at the angiotensin-I-converting enzyme (ACE)-insertion/deletion
      polymorphism has been associated with an increased risk of developing several
      pathological processes, such as coronary heart disease and ventricular
      hypertrophy. Individuals with the DD genotype show a significantly increased left
      ventricular mass in response to physical training, compared to the II genotype
      (which would be associated with the lowest plasma ACE levels) and the ID
      genotype. The II genotype has been linked to a greater anabolic response. In
      accordance with a role for ACE in the response to rigorous physical training, a
      higher frequency of the I allele has been reported to exist among elite rowers
      and high-altitude mountaineers. Sixty elite (professional) athletes (25 cyclists,
      20 long-distance runners, and 15 handball players), and 400 healthy controls were
      genotyped for the DNA polymorphisms of the ACE, angiotensinogen (Ang) and
      angiotensin receptor type 1 (AT1) genes. Plasma ACE levels showed a strong
      correlation with the I/D genotype in our population. The I-allele occurred at a
      significantly higher frequency in athletes compared to controls (P = 0.0009).
      Gene and genotype frequencies for the Ang and AT1 polymorphisms did not differ
      between athletes and controls. Since the frequency of the ACE I allele was
      significantly increased among our elite athletes, we conclude that the ACE
      polymorphism represents a genetic factor that contributes to the development of
      an elite athlete.

PMID- 10879453
TI  - Hormonal responses to high- and moderate-intensity strength exercise.
AB  - The hormonal responses of nine male, strength athletes to strength exercise were
      examined. The athletes performed one moderate- and one high-intensity strength
      exercise workout. In the high-intensity workout, the load was 100% of each
      subject's three-repetition maximum (3-RM) for squats and front squats, and 100%
      of each subject's six-repetition maximum (6-RM) for leg extensions. In the
      moderate-intensity workout, the load was 70% of the high-intensity protocol. Rest
      periods between sets were 4-6 min for both workouts. Blood samples were taken
      before, 30 min into, and every 15 min for the 1st h after exercise, and then 3,
      7, 11, 22 and 33 h after exercise, thus allowing examination of both the acute
      and prolonged hormonal responses. Blood samples were analyzed for testosterone,
      luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol,
      adrenocorticotrophic hormone (ACTH), growth hormone (GH), insulin-like growth
      factor (IGF-1), insulin, sex hormone binding globulin, creatine kinase, total
      protein, glucose and lactate. The acute responses of testosterone and cortisol
      were greater during the high-intensity protocol as compared to the moderate
      intensity protocol. The cortisol response was associated with an increase in ACTH
      concentration. LH and FSH showed no response to either protocol. Acute GH
      responses were not different between protocols. There were great inter-individual
      differences in acute GH responses to both protocols. There were no significant
      differences between protocols with regard to prolonged responses for any hormone.
      In both trials, IGF-1 concentrations were significantly lower at 0800 hours the
      morning after exercise as compared to concentrations found at 0800 hours the
      morning before exercise. The mechanisms responsible for reducing IGF-1
      concentration in these trials are unclear, and it is not known if this reduction
      observed 22 hours after exercise is of physiological significance.

PMID- 10879454
TI  - Significance of peripheral afferent input to the alpha-motoneurone pool for
      enhancement of tremor during an isometric fatiguing contraction.
AB  - The objective of this study was to investigate the contribution of peripheral
      afferent input to the enhancement of isometric tremor during a sustained
      submaximal isometric contraction. It was hypothesised that during muscle fatigue,
      when excitatory drive is high, peripheral afferent input may augment oscillations
      in the stretch reflex arc and result in bursting motor-unit activity and
      increased tremor. Nine healthy subjects maintained isometric plantar flexions at
      30% of their maximum voluntary contraction until the limit of endurance, under
      three test conditions. Two paradigms were used to reduce afferent input to the
      triceps surae alpha-motoneurone pool: (1) continued vibration of the Achilles
      tendon, and (2) ischaemic partial block of the tibial nerve. These were compared
      to a control experiment, in which there was no intervention. By recording H
      reflexes from the gastrocnemius and soleus muscles, it was possible to assess the
      effectiveness of reducing the afferent input. When H-reflex suppression had
      stabilised, the fatiguing contraction was commenced and tremor was computed from
      the continuously recorded torque signal. Superimposed maximum twitches were
      elicited as indirect measures of excitatory drive. The increase in tremor root
      mean square throughout the fatiguing contraction was significantly less for both
      the vibration and ischaemic conditions. Furthermore, tremor mean power frequency
      decreased significantly with endurance time in the control experiment, while no
      significant change was seen in the other two experimental conditions. It is
      concluded that the enhancement of isometric tremor seen during a fatiguing
      submaximal isometric contraction is facilitated by peripheral afferent input to
      the alpha-motoneurone pool.

PMID- 10879455
TI  - Effects of dynamic ischaemic training on human skeletal muscle dimensions.
AB  - The effect of training under conditions of local leg ischaemia on muscle area and
      fibre dimensions was studied in nine males. Leg ischaemia was induced by
      enclosing the legs in a pressure chamber and sealing the opening with a rubber
      membrane at the level of the crotch. Air pressure over the legs was 50 mmHg. The
      subjects performed 16 sessions (45 min) of one-legged supine strenuous ischaemic
      training during 4 weeks. Exercise intensity was maintained as high as possible
      during the whole session. The contralateral leg served as a control leg and
      remained passive during exercise. Before and after the training period, muscle
      fibre dimensions were determined from biopsy samples taken from the m. vastus
      lateralis, and leg muscle dimensions were assessed by magnetic resonance imaging
      (MRI). In the trained leg, mean fibre area increased by 12% (P < 0.05). The MRI
      assessed cross-sectional area of the vastus group increased by 4% (P = 0.01). In
      the control leg, mean fibre area and the cross-sectional area of the vastus group
      were unchanged, while those of the adductor muscle group decreased by 4% (P <
      0.05). It is concluded that a short period of strenuous ischaemic endurance
      training increases the cross-sectional area of the ischaemically trained muscle
      group, as measured both by MRI and from muscle biopsy samples. In contrast, the
      adductor muscles in the contralateral thigh showed a decreased cross-sectional
      area (as assessed by MRI), possibly due to the effects of the strenuous
      contralateral training, by mechanisms that have yet to be identified.

PMID- 10879456
TI  - Endotoxaemia does not limit heat tolerance in rats: the role of plasma
      lipoproteins.
AB  - Severe hyperthermia disrupts the intestinal barrier, allowing bacterial
      lipopolysaccharides (LPS) to enter the bloodstream. Since the symptoms of heat
      stroke resemble those of endotoxic shock, there is a common belief that
      endotoxaemia induces heat stroke. Therefore, we studied the effects of different
      doses, from moderate to sublethal, of Escherichia coli LPS and an antipyretic
      (indomethacin) upon the temperature equilibrium of the brain and body of rats
      exposed to a constant ambient temperature of 38 degrees C. The animals were then
      heated until they developed heat stroke, which was identified using a critical
      thermal maximum (CTM) behavioural test. In separate experiments on defence
      against endotoxaemia, we compared plasma lipid composition in rats exposed to a
      sublethal dose of LPS, hyperthermia and heat stroke. Neither LPS nor
      indomethacin, injected into rats while they were in a hyperthermic steady-state
      condition of 40-41 degrees C, influenced their thermal equilibrium. Unexpectedly,
      moderate doses of LPS significantly elevated the thermal tolerance of rats, such
      that the mean (SEM) CTM value of body temperature was raised from 42.7 (0.3)
      degrees C to 43.1 (0.1) degrees C (P < 0.05). Indomethacin and huge doses of LPS
      failed to induce any change in this parameter. The sublethal dose of LPS did not
      induce mortality in rats subjected to heat stroke. Hyperthermic steady-state
      conditions and heat stroke alone significantly decreased plasma concentrations of
      cholesterol, triglyceride and high-density lipoproteins, while the concentrations
      of low-density lipoproteins increased. A similar pattern of changes was recorded
      in normothermic rats injected with a sublethal dose of LPS. In conclusion,
      endotoxaemia in heat-stressed rats induces neither a secondary increase in their
      core temperature nor a decrease in their ultimate thermal tolerance. Low-density
      lipoproteins are likely to protect heat-stressed animals against endotoxin
      induced death.

PMID- 10879457
TI  - Influence of acute submaximal exercise on T-lymphocyte suppressor cell function
      in healthy young men.
AB  - A defect in T-lymphocyte suppressor cell function has been reported to occur in a
      number of autoimmune diseases. The influence of exercise on suppressor cell
      function has not been determined in individuals with autoimmune diseases, nor has
      it been determined in healthy individuals. The purpose of this investigation was
      to determine the effect of an acute bout of submaximal exercise on suppressor
      cell function in healthy males. Each subject (n = 10) completed an exercise trial
      (E; 1 h of cycle ergometry at 70.6% of maximal oxygen uptake, followed by 2 h of
      recovery) and a resting trial (R; 3 h of seated rest), separated by at least 1
      week. Treatment (E or R) order was counterbalanced. Venous blood samples were
      obtained pre-exercise (PRE), immediately after exercise (POST), and 2 h post
      exercise (2HPOST), and at the same time points in the R trial. Lymphocyte
      phenotype percentages were determined by flow cytometry, while concanavalin-A
      induced suppressor cell function was determined on peripheral blood mononuclear
      cells. No change was observed in the percentage of T-cytotoxic/suppressor cells.
      Suppressor cell function was significantly different between treatments, with the
      POST E value [mean (SD) 56.8 (1.6)%] being higher than the POST R value [41.7
      (1.9)%]. No significant difference was observed 2HPOST. In conclusion, acute
      submaximal exercise resulted in a transient increase in suppressor cell function
      in healthy males.

PMID- 10879458
TI  - Atrial automaticity and atrioventricular conduction in athletes: contribution of
      autonomic regulation.
AB  - Little is known about the sinoatrial automatism and atrioventricular conduction
      of trained individuals who present a normal resting electrocardiogram. We used
      transesophageal atrial stimulation, a minimally invasive technique, to evaluate
      aerobically trained athletes (n = 10) and sedentary individuals (n = 10) with
      normal resting electrocardiograms, to test the hypothesis that parasympathetic
      tone, as detected by heart rate variability, could be associated with changes in
      sinoatrial automatism and atrioventricular conduction. Corrected sinus node
      recovery time tended to be longer in athletes than in sedentary individuals, but
      this difference did not reach statistical significance. The Wenckebach point
      occurred at a lower rate in athletes than in the controls. Over a 24-h period of
      measurement, the mean RR interval was longer in the athletes than in the
      sedentary individuals. The mean square root of successive differences (rMSSD)
      tended to be higher in athletes than in controls, but this difference did not
      reach statistical significance. There was a moderate correlation (r = 0.48, P <
      0.05) between the index of atrioventricular conduction, the rate at the
      Wenckebach point, and the logarithmically transformed rMSSD. Thus, as a corollary
      to its effects on the sinus node, where increased parasympathetic tone, decreased
      sympathetic tone, and non-autonomic components may contribute to sinus
      bradycardia, it is possible that athletic training may also induce intrinsic
      adaptations in the conduction system, which could contribute to the higher
      prevalence of atrioventricular conduction abnormalities observed in athletes.

PMID- 10879459
TI  - Peak power assessment in isokinetic dynamometry.
AB  - The purpose of the present study was to establish a method by which to derive
      accurate and valid isokinetic peak power measurements. For this purpose, peak
      power was calculated as the product of: (1) preselected angular velocity and peak
      moment without considering the angular velocity at peak moment (method I), (2)
      actual angular velocity and the respective moment values at that time (method
      II), (3) instant actual angular velocity at the point of peak moment and peak
      moment (method III), and (4) actual constant angular velocity and the highest
      moment during this period (method IV). Ten subjects performed concentric knee
      extensions at 30, 90, 180 and 300 degrees/s on a Lido Active isokinetic
      dynamometer. The product of moment and actual angular velocity derived from the
      angular displacement data was used to measure peak power in methods II, III and
      IV. Significant differences were found between the four methods. Method I results
      in artificial peak power and methods II and III do not produce actual isokinetic
      peak power. The latter can only be assessed using method IV. It was concluded
      that method IV (highest moment during constant angular velocity period) must be
      used in order to obtain valid, accurate and comparable isokinetic peak power
      values.

PMID- 10879460
TI  - Cloning and sequencing of pel gene responsible for CMCase activity from Erwinia
      chrysanthemi PY35.
AB  - The phytopathogenic bacterium Erwinia chrysanthemi secretes multiple isozymes of
      plant cell wall disrupting enzymes such as pectate lyase and endoglucanase. We
      cloned genomic DNA from Erwinia chrysanthemi PY35. One of the E. coli XL1-Blue
      clones contained a 5.1-kb BamHI fragment and hydrolyzed carboxymethyl cellulose
      and polygalacturonic acid. By subsequent subcloning, we obtained a 2.9-kb
      fragment (pPY100) that contained the pel gene responsible for CMCase and pectate
      lyase activities. The pel gene had an open reading frame (ORF) of 1,278 bp
      encoding 425 amino acids with a signal peptide of 25 amino acids. Since the
      deduced amino acid sequence of this protein was very similar to that of PelL of
      E. chrysanthemi EC16, we concluded that it belonged to the pectate lyase family
      EC 4.2.2.2, and we designated it PelL1. Sequencing showed that the PeIL1 protein
      contains 400 amino acids and has a calculated pI of 7.15 and a molecular mass of
      42,925 Da. The molecular mass of PelL1 protein expressed in E. coli XL1-Blue, as
      analyzed by SDS-PAGE, appeared to be 43 kDa. The optimum pH for its enzymatic
      activity was 9, and the optimum temperature was about 40 decreased C.

PMID- 10879461
TI  - Purification and characterization of aspartic proteinase from sunflower seeds.
AB  - Aspartic proteinases were purified from sunflower seed extracts by affinity
      chromatography on a pepstatin A-EAH Sepharose column and by Mono Q column
      chromatography. The final preparation contained three purified fractions. SDS
      PAGE showed that one of the fractions consisted of disulfide-bonded subunits (29
      and 9 kDa), and the other two fractions contained noncovalently bound subunits
      (29 and 9 kDa). These purified enzymes showed optimum pH for hemoglobinolytic
      activity at pH 3.0 and were completely inhibited by pepstatin A like other
      typical aspartic proteinases. Sunflower enzymes showed more restricted
      specificity on oxidized insulin B chain and glucagon than other aspartic
      proteinases. The cDNA coding for an aspartic proteinase was cloned and sequenced.
      The deduced amino acid sequence showed that the mature enzyme consisted of 440
      amino acid residues with a molecular mass of 47,559 Da. The difference between
      the molecular size of purified enzymes and of the mature enzyme was due to the
      fact that the purified enzymes were heterodimers formed by the proteolytic
      processing of the mature enzyme. The derived amino acid sequence of the enzyme
      showed 30-78% sequence identity with that of other aspartic proteinases.

PMID- 10879462
TI  - Characterization of acid-stable glucose isomerase from Streptomyces sp., and
      development of single-step processes for high-fructose corn sweetener (HFCS)
      production.
AB  - The glucose isomerase from Streptomyces olivaceoviridis E-86 was purified by
      chromatographic procedures, showing one single protein band in the SDS-PAGE. The
      enzyme had high acid stability, and there was no loss in enzyme activity at pH
      5.0 after incubation at 60 degrees C for 30 hr. The enzyme had sufficients
      activity at 60 degrees C, pH 5.5, (which is the reaction condition for a single
      step process with a glucoamylase from A. niger), and at 58 degrees C, pH 6.0,
      (condition with a glucoamylase from R. niveus). By using this acid-stable glucose
      isomerase, a single-step process to produce high-fructose corn sweetener (HFCS)
      from liquefied starch was formed without any reductant or other reagents for
      enzyme stabilization. The HFCS produced was about fifty percent fructose and less
      than 1.5% unknown oligosaccharides.

PMID- 10879463
TI  - Amino acid sequence of a nuclease (nuclease Le1) from Lentinus edodes.
AB  - The fruit bodies of Lentinus edodes produce two acid nucleases, nucleases Le1 and
      Le3, both of which are thought to be candidates for the enzymes producing a tasty
      substance, 5'-GMP. To obtain the basic information on the mechanism of production
      of 5'-GMP, and structure-function relationship of these nucleases, the primary
      structure of nuclease Le1 was estimated by both protein chemistry and gene
      cloning. Nuclease Le1 is a glycoprotein and consists of 290 amino acid residues,
      and about 2 and 6 residues of hexosamine and neutral sugar, respectively. The
      nucleotide sequence of cDNA and genomic DNA encoding nuclease Le1 indicated the
      presence of 20 amino acid residues of a signal peptide. Nuclease Le1 has 115 and
      108 residues of identical amino acid residues with nucleases P1 and S,
      respectively. The amino acid residues concerning the coordination with Zn2+ in
      nuclease P1 are all conserved in nuclease Le1. Nuclease Le1 contains 8 half
      cystine residues and 4 of them are located at the same places as those of
      nucleases P1 and S.

PMID- 10879464
TI  - Binding of barley and wheat alpha-thionins to polysaccharides.
AB  - An antimicrobial peptide termed BCP-2 was purified from barley grain by chitin
      affinity treatment and HPLC. The results of amino acid analysis and mass
      spectrometry of BCP-2 indicate that the peptide is very similar to barley alpha
      thionin. BCP-2 and wheat alpha1-thionin were also bound to beta-glucan but not to
      starch. The binding of BCP-2 to laminarin (beta-1,3-1,6-glucan) and
      laminarioligosaccharides was supported by fluorescence polarization data. This is
      the first report on the binding of alpha-thionins to polysaccharide containing
      chitin and beta-1,3-glucan, which construct fungal cell walls.

PMID- 10879465
TI  - Effect of dietary chitosans with different viscosity on plasma lipids and lipid
      peroxidation in rats fed on a diet enriched with cholesterol.
AB  - To investigate the effect of dietary chitosan on lipid metabolism, male SD
      (Sprague-Dawley) rats were fed a cholesterol-enriched diet containing 5%
      cellulose (CE), 5% chitosan (CCS; high viscosity), or 5% chitosan (FCS; low
      viscosity) for 4 weeks. The two types of chitosan with a comparable degree of
      deacetylation had a different molecular weight and intrinsic viscosity.
      Significantly (p < 0.05) lower plasma total cholesterol, LDL-cholesterol and VLDL
      cholesterol concentrations were observed in the rats fed on the chitosan diets.
      In addition, chitosan significantly increased the fecal cholesterol and
      triglyceride contents. Although no significant difference in body weight was
      found among the dietary groups, the rats fed on the chitosan diets had lower
      relative liver weight when compared with those fed on the cellulose diet. Both of
      the chitosan groups had significantly lower liver total lipid and total
      cholesterol contents compared to the cellulose group, although the FCS group was
      less effective. The plasma and liver thiobarbituric acid reactive substances
      (TBAR) values were similar in the CE and FCS groups, while the CCS group had
      increased liver TBAR values. Although a significant increase in liver glucose-6
      phosphate dehydrogenase activity was observed in the CCS group, no significant
      change was found in the FCS group. The observed influence of chitosans with
      different viscosity on the plasma lipid level, liver lipids and lipid
      peroxidation suggests that, while the hypocholesterolemic action of chitosans
      with different viscosity was similar, changes in the liver lipids and liver
      peroxidation status depended on their molecular weight when the deacetylation
      degree was comparable.

PMID- 10879466
TI  - End-product regulation and kinetic mechanism of guanosine-inosine kinase from
      Escherichia coli.
AB  - Escherichia coli guanosine-inosine kinase was overproduced, purified, and
      characterized. The native and subunit molecular weights were 85,000 and 45,000,
      respectively, indicating that the enzyme was a dimer. A pI of 6.0 was obtained by
      isoelectric focusing. In addition to ATP, it was found that deoxyadenosine 5'
      triphosphate, UTP, and CTP could serve as phosphate donors. The phosphate
      acceptors were guanosine, inosine, deoxyguanosine and xanthosine, but not
      adenosine, cytidine, uridine, or deoxythymidine. Maximum activity was attained at
      an ATP/Mg2+ concentration ratio of 0.5. In the presence of pyrimidine
      nucleotides, enzyme activity was slightly increased, while it was markedly
      inhibited by GDP and GTP. Initial velocity and product inhibition studies support
      an ordered Bi Bi mechanism in which guanosine was the first substrate to bind and
      GMP was the last product to be released. Guanosine kinase may be a regulatory
      enzyme that has a role in modulating nucleotide levels.

PMID- 10879467
TI  - Transport of pyruvate in Saccharomyces cerevisiae and cloning of the gene encoded
      pyruvate permease.
AB  - Pyruvate uptake in Saccharomyces cerevisiae was not observed at 0 degrees C and
      was prevented by the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP).
      The initial uptake rate of S. cerevisiae kyokai No. 901 was maximum at pH 6 and
      Km = 4.1 mM. It seemed that lactate inhibited the pyruvate uptake competitively
      from the results of the Lineweaver-Burk plots. The inhibition constant (Ki) in
      the presence of 3 mM lactate was 1.6 mM. The pyruvate uptake was inhibited by D
      glucose and deoxyglucose, but not by L-glucose, acetate or ethanol. Mutants of
      laboratory strain No. 5022 ((a) his(2,6), ura3) deficient in pyruvate uptake were
      isolated from fluoropyruvate resistant mutants. Transformation of the mutant with
      a yeast genomic library allowed the isolation of the gene JEN1 (YKL217w), which
      restored pyruvate uptake. Disruption of JEN1 abolished the uptake of pyruvate and
      gained the resistance against fluoropyruvate. The results indicate that no other
      monocarboxylate permease is able to efficiently transport pyruvate in S.
      cerevisiae.

PMID- 10879468
TI  - Design of a novel membrane-destabilizing peptide selectively acting on acidic
      liposomes.
AB  - The design of amphipathic peptides resulted in a novel peptide with a selective
      ability to destabilize lipid bilayers of acidic liposomes. The newly synthesized
      peptide, termed mast 21, is a 21-residue long amino acid chain and can only act
      effectively on acidic liposomes lacking cholesterol. Moreover, mast 21 killed
      gram-positive and gram-negative bacteria, and it had no hemolytic activity. The
      antimicrobial and hemolytic activities paralleled the results of membrane
      destabilizing activity using liposomes. Circular dichroism and Trp-fluorescence
      emission spectra showed changes in the peptide conformation and circumstances
      around the peptide during interaction with liposomes. These changes were
      consistent with an increased alpha-helical content and a less polar environment
      for the tryptophan residue of the peptide. Mast 21 was observed under dark-field
      microscopy in real time attacking liposomes. Acidic liposomes were attacked,
      which resulted in peeling of the lipid bilayer with its subsequent destruction.

PMID- 10879469
TI  - The pathway of dephosphorylation of myo-inositol hexakisphosphate by phytases
      from wheat bran of Triticum aestivum L. cv. Nourin #61.
AB  - Phytases are the primary enzymes responsible for the hydrolysis of phytic acid,
      myo-inositol-1, 2, 3, 4, 5, 6-hexakisphosphate (InsP6). The pathway of hydrolysis
      of InsP6 by phytase from wheat bran of Triticum aestivum L. cv. Nourin #61 is
      proved in this study. Structures of the intermediates were established by a
      variety of nuclear magnetic resonance techniques (1H-, two-dimensional 1H-1H
      coupling-correlation spectra and two-dimensional 31P-1H correlation spectra), gas
      chromatography, and bioassay. On the basis of the structures identified, initial
      hydrolysis of the phosphate ester occurs at the D/L-4 position of InsP6 to yield
      D/L-Ins (1, 2, 3, 5, 6) P5. After the dephosphorylation, the pathway of
      dephosphorylation is divided into two routes. The main route proceeds via D/L-Ins
      (1, 2, 5, 6) P4, D/L-Ins (1, 2, 6) P3 and D/L-Ins (1, 2) P2, while the minor
      route proceeds via D/L-Ins (1, 2, 3, 6) P4, Ins (1, 2, 3) P3 and D/L-Ins (1, 2)
      P2. D/L-Ins (1, 2) P2 is hydrolyzed at the D/L-1 or 2-position, and finally myo
      inositol is produced.

PMID- 10879470
TI  - Induction of oxidatively modified proteins in skeletal muscle by electrical
      stimulation and its suppression by dietary supplementation of (-)
      epigallocatechin gallate.
AB  - The oxidative stress produced by electrical stimulation-induced muscle
      contraction was examined in the skeletal muscle proteins of rats that had been
      fed on the dietary flavonoid, (-)-epigallocatechin gallate (EGCg). Electrical
      stimulation of the rat leg muscle every second day for a two-week period resulted
      in an increased (p < 0.05) muscle weight and accumulation of oxidatively induced
      modified proteins. Similar stimulation conducted every day for only one week had
      no effect on the muscle weight or protein oxidation, although the rate of protein
      degradation increased. Rats fed on a 20% casein diet supplemented with 0.1% EGCg
      for 2 weeks responded to the electrical stimulation of muscle contraction by
      reducing the increased muscle protein carbonyl content when compared to their
      counterparts fed on a control diet. There was no change in activity of
      antioxidative enzymes in muscle tissue of the EGCg-fed rats receiving electrical
      stimulation. The results of this study show that the antioxidative property of
      EGCg was effective for suppressing oxidative modification of the skeletal muscle
      protein induced by electrical stimulation. This finding demonstrates that EGCg
      has a beneficial effect in vivo on the free radical-mediated oxidative damage to
      muscle proteins.

PMID- 10879471
TI  - Avoidance of solidification of sesame oil at low temperature by self
      interesterification with immobilized lipase.
AB  - To reduce the freezing point of sesame oil, the lipase-catalyzed
      interesterification of sesame oil in a solvent free system was studied. The
      lipase was immobilized on Celite and refined sesame oil was used as the only
      substrate for the reaction. After interesterification, the oil did not solidify
      at 0 degrees C even after 24 h, and even longer storage at 2-4 degrees C did not
      result in solidification. The change of physical behavior was investigated with a
      differential scanning calorimeter and X-ray diffraction, and reduction in the
      thermodynamic and crystallographic stability of the interesterified oil was
      demonstrated. The change in triacylglycerol species composition after the
      reaction was analyzed, showing that content of trisaturated acylglycerol was
      decreased.

PMID- 10879472
TI  - Alteration of the self-incompatibility phenotype in Brassica by transformation of
      the antisense SLG gene.
AB  - Self-incompatible (SI) Brassica rapa (syn. B. campestris) was transformed with an
      antisense SLG gene by using SLG8 cDNA isolated from the B. campestris S8
      homozygote. Two transformed lines were obtained and analyzed. Northern blot and
      Western blot analyses revealed that endogenous SLG and SRK were greatly reduced
      of the transcriptional and translational levels in the transformant. Pollination
      experiments confirmed that their SI phenotype had broken down. In addition, the
      progeny with the antisense SLG gene, resulting from self- or cross-pollination of
      the transgenic plant, also showed the self-compatible phenotype. The breakdown of
      SI in the tranformants was due to the change in property of the stigma and not of
      the pollen. These results provide strong evidence that SLG and/or SRK is
      implicated in the pollen-stigma recognition of SI and that they act only as
      stigmatic factors.

PMID- 10879473
TI  - Induction of N-hydroxycinnamoyltyramine synthesis and tyramine N
      hydroxycinnamoyltransferase (THT) activity by wounding in maize leaves.
AB  - Both N-p-coumaroyl- and N-feruloyltyramine accumulated in response to wounding in
      leaf segments of maize. The amount of N-hydroxycinnamoyltyramines started to
      increase 3-6 h after wounding and peaked at 12 h. Thereafter, the amount of N-p
      coumaroyltyramine decreased rapidly, while the N-feruloyltyramine content
      remained at a high level. The accumulation of N-hydroxycinnamoyltyramines was
      accompanied by an increase in the tyramine N-hydroxycinnamoyltransferase (THT)
      activity. This increase was initially detected 3 h after wounding and reached a
      maximum at 36 h, the level of activity being 40 and 11 times that in the leaves
      before wounding and in the control leaves, respectively. Partial purification of
      THT from wounded leaves by (NH4)2SO4 precipitation and subsequent two steps of
      anion-exchange chromatography resulted in a 12.5-fold increase in specific
      activity. Kinetic studies with this partially purified enzyme revealed that the
      best substrates were tyramine and feruloyl-CoA, although tryptamine and sinapoyl
      CoA also efficiently served as substrates. The apparent native molecular weight
      of the enzyme was determined by gel filtration as 40 kDa.

PMID- 10879474
TI  - Application of a bioluminescence method for the beer industry: sensitivity of
      MicroStar-RMDS for detecting beer-spoilage bacteria. Rapid Microbe Detection
      System.
AB  - We set up the original operating conditions of the MicroStar-Rapid Microbe
      Detection System (RMDS) to suppress false positives, which have kept this system
      from practical. The detection limit of our system was between 6.3 x 10(-16) mol
      and 3.1 x 10(-16) mol in terms of the amount of ATP, which is approximately equal
      to the ATP content of one yeast cell or 50 lactic acid bacteria cells. The
      detection time and the detection count were compared between the RMD method and
      the conventional plate count method (C.P.C. method) using 23 test samples of beer
      spoilage Lactobacillus brevis. Judging from the detection time and detection
      count, 16-24 hours of cultivation for the RMD method corresponded to 40-96 hours
      of cultivation for the C.P.C. method. The RMD method reached a useful level for
      our practical use at the point of sensitivity.

PMID- 10879475
TI  - 1,1-Diphenyl-2-picrylhydrazyl radical-scavenging compounds from soybean miso and
      antiproliferative activity of isoflavones from soybean miso toward the cancer
      cell lines.
AB  - Guided by their DPPH radical-scavenging activity, nine compounds were isolated
      from soybean miso. Of these, 8-hydroxydaidzein, 8-hydroxygenistein and syringic
      acid had as high DPPH radical-scavenging activity as that of alpha-tocopherol.
      The antiproliferative activity of four of the isolated isoflavones toward three
      cancer cell lines was examined. 8-Hydroxygenistein showed the highest activity
      (IC50=5.2 microM) toward human promyelocytic leukemia cells (HL-60).

PMID- 10879476
TI  - Alpha-amylase inhibitors from roselle (Hibiscus sabdariffa Linn.) tea.
AB  - A roselle (Hibiscus sabdariffa Linn.) tea extract was found to have high
      inhibitory activity against porcine pancreatic alpha-amylase. Hibiscus acid and
      its 6-methyl ester were respectively isolated as active principles from the 50%
      methanol and acetone extracts of roselle tea. The activity of each isolate was
      compared to that of structurally related citric acid, a previously known
      inhibitor of fungal alpha-amylase.

PMID- 10879477
TI  - Identification of new geometric isomers of methyl linoleate hydroperoxide and
      their chromatographic behavior.
AB  - New geometric isomers, methyl (9Z,11Z)-13-hydroperoxy-9,11-octadecadienoate and
      methyl (10Z,12Z)-9-hydroperoxy-10,12-octadecadienoate, were proved to be present
      in methyl linoleate hydroperoxide produced by autoxidation. They were identified
      from their UV, MS, and 1H-NMR spectra after conversion to the corresponding oxo
      derivatives: methyl (9Z,11Z)-13-oxo-9,11-octadecadienoate and methyl (10Z,12Z)-9
      oxo-10,12-octadecadienoate. Their chromatographic behavior is described.

PMID- 10879478
TI  - Effect of oxidized cholesterol on age-associated changes to immune parameters in
      spleen lymphocytes and peritoneal exudate cells derived from rats.
AB  - The effects of oxidized cholesterol on immune parameters were examined by using
      spleen lymphocytes and peritoneal exudate cells (PEC) derived from 5-week-
      (Young) and 9-month-old (Adult) rats. The immunoglobulin (Ig) G and IgM
      production was inhibited by oxidized cholesterol in the rats of both ages when
      lymphocytes were exposed to 30 micrograms/ml of oxidized cholesterol for 24 hr.
      The intracellular IgA level was also lowered by 30 micrograms/ml of oxidized
      cholesterol, irrespective of age. In contrast, IgE production was significantly
      increased by the addition of 30 micrograms/ml of oxidized cholesterol in only
      young lymphocytes. Moreover, oxidized cholesterol enhanced the intracellular
      histamine accumulation in only adult PEC, although the total histamine level
      produced by PEC was similar in the rats of both ages. These results thus suggest
      the possibility that oxidized cholesterol can have different effects on the age
      related modulation of immune functions such as Igs production and histamine
      release.

PMID- 10879479
TI  - Cloning and expression of bovine imc-415 cDNA from mammary gland.
AB  - Bovine imc-415 cDNA was cloned from mammary gland using RACE PCR; it coded for
      245 amino acids. The deduced amino acid sequence of mouse and human showed about
      94% identity. Expression of bovine imc-415 increased about 40% in involuted
      mammary tissues compared with lactating tissues.

PMID- 10879480
TI  - Purification and some properties of an aminopeptidase from the seeds of Cannabis
      sativa.
AB  - An aminopeptidase (HSA) with a molecular mass of 78 kDa was purified from hemp
      (Cannabis sativa) seeds. The activity was inhibited by monoiodeacetic acid, p
      chloromercuri-phenylsulfonic acid, and Zn2+ ion. The specificity of HSA was
      similar to that of a leucyl aminopeptidase [EC 3.4.11.1] from mammalian cytosol.
      However, other enzyme properties were different from these of leucyl
      aminopeptidase.

PMID- 10879481
TI  - Application of the random arbitrary primed polymerase chain reaction differential
      display method to isolate genes of cholesterol metabolism-related proteins from
      rat liver.
AB  - The random arbitrary primed (RAP) polymerase chain reaction (PCR) differential
      display (DD) method was applied to isolate genes related to cholesterol
      metabolism from exogenously hypercholesterolemic (ExHC) rats and the progenitor,
      SD rats. Forty-seven trials of RAP-PCR DD resulted in the isolation of 37 clones
      differing in strain, cholesterol supplementation or their interaction. Among
      their fingerprints, five clones gave reproducible patterns by a Northern blotting
      analysis. The sequence of two clones with lower mRNA abundance in ExHC rats than
      in SD rats was homologous to that of fatty acid synthase and oxalyl-CoA
      decarboxylase. Two other clones with higher mRNA on the n-cholesterol diet were
      matrin F/G protein and the NMDA receptor glutamate-binding subunit. The other
      clone with higher mRNA abundance in ExHC rats on the cholesterol diet was
      myelodysplasia/myeloid leukemia factor 2. Fifteen trials of reverse transcriptase
      (RT)-PCR DD yielded 10 clones, but none of the fingerprints were reproduced by
      the Northern blotting analysis. These results indicate that RAP-PCR DD is an
      appropriate alternative to RT-PCR DD for isolating the genes involved in
      hypercholesterolemia.

PMID- 10879482
TI  - Inhibition of fungal cell wall synthesizing enzymes by trans-cinnamaldehyde.
AB  - This study examined the inhibitory effects of trans-cinnamaldehyde (CA), an
      aromatic aldehyde derived from Cinnamomi Cortex, on Saccharomyces cerevisiae cell
      wall synthesizing enzymes in vitro. This compound was found to be a
      noncompetitive inhibitor of beta-(1,3)-glucan synthase and a mixed inhibitor of
      chitin synthase 1 with 50% inhibitory concentrations (IC50) of 0.84 and 1.44 mM,
      respectively. Chitin synthases 2 and 3 were less sensitive than chitin synthase 1
      to CA. CA can be useful as a model compound of cell wall inhibitors for the
      development of effective antifungal agents.

PMID- 10879483
TI  - Substrate specificity of regiospecific desaturation of aliphatic compounds by a
      mutant Rhodococcus strain.
AB  - Substrate specificity of cis-desaturation of alipahtic compounds by resting cells
      of a mutant, Rhodococcus sp. strain KSM-MT66, was examined. Among substrates
      tested, the rhodococcal cells were able to convert n-alkanes (C13-C19), 1
      chloroalkanes (C16 and C18), ethyl fatty acids (C14-C17) and alkyl (C1-C4) esters
      of palmitic acid to their corresponding unsaturated products of cis
      configuration. The products from n-alkanes and 1-chloroalkanes had a double bond
      mainly at the 9th carbon from their terminal methyl groups, and the products from
      acyl fatty acids had a double bond mainly at the 6th carbon from their carbonyl
      carbons.

PMID- 10879484
TI  - Purification of alginate oligosaccharides with root growth-promoting activity
      toward lettuce.
AB  - Sodium alginate was degraded by alginate lyase from Corynebacterium sp., and the
      product was purified by an ultrafiltration (UF) membrane module. The UF treatment
      was carried out at a transmembrane pressure of 0.15 MPa and a flow velocity of
      0.6 m/s in the cross-flow mode, and non-degraded alginate was almost completely
      removed. The alginate oligosaccharide obtained was a mixture of di- to
      octasaccharides and had promoting activity toward lettuce root elongation (about
      2-fold compared with the control) in the concentration range of 200-3000
      microg/ml. The effect of the degree of polymerization on this activity was
      examined by using each oligosaccharide fractionated by gel chromatography. The
      tri-, tetra-, penta- and hexasaccharides were each found to have root growth
      promoting activity in a lettuce bioassay.

PMID- 10879485
TI  - Syntheses of (+/-)-methyl 6'alpha-demethyl-6'alpha-cyanoabscisate and (+/-)
      methyl 6'alpha-demethyl-6'alpha-methoxycarbonylabscisate.
AB  - New abscisic acid analogs possessing a cyano or methoxycarbonyl group at the
      6'alpha-position of methyl abscisate were synthesized by regioselective
      hydrocyanation. These compounds had weak activity in the rice second leaf sheath
      elongation test.

PMID- 10879486
TI  - Apoptosis induced by the flavonoid from lemon fruit (Citrus limon BURM. f.) and
      its metabolites in HL-60 cells.
AB  - The flavonoid from lemon fruit (Citrus limon BURM. f.) and its metabolites,
      particularly eriodictyol, 3,4-dihydroxyhydrocinnamic acid, and phloroglucinol had
      the function of DNA fragmentation in HL-60 cells when analyzed by flow cytometry.
      An apoptotic DNA ladder and chromatin condensation were observed in HL-60 cells
      when treated with these compounds. The caspase inhibitor prevented DNA
      fragmentation. These compounds are anticipated to be useful for medical purposes.

PMID- 10879487
TI  - Use of Bacillus brevis for synthesis and secretion of Des-B30 single-chain human
      insulin precursor.
AB  - A synthetic gene encoding a single chain human insulin precursor [B-chain (1-29)
      A-chain] linked to the C-terminal lysine of human epidermal growth factor (1-28)
      (EGF-SCI) was constructed. This gene was expressed using Bacillus brevis. EGF-SCI
      was isolated from the supernatant of the culture broth. Treatment of EGF-SCI with
      lysyl endopeptidase resulted in the formation of des-B30 human insulin. The
      identification of the formed des-B30 human insulin was made by the measurement of
      molecular weight and amino acid analysis. The binding coefficient to anti-human
      insulin antibody was comparable to that of human insulin.

PMID- 10879488
TI  - A simple and rapid extraction of high molecular weight chromosomal DNA from
      Bacillus subtilis protoplasts for cosmid cloning and interspecific
      transformation.
AB  - After conversion of Bacillus subtilis vegetative cells to protoplasts, a simple
      and rapid method for extracting high-molecular-weight chromosomal DNA was devised
      with the inclusion of bovine serum albumin and phenol-chloroform treatments. The
      DNA sample thus prepared was the size of 100-450 kb and could be used for cosmid
      cloning and interspecific transformation.

PMID- 10879489
TI  - Identification of the UV-responsive sequence in the human tissue plasminogen
      activator gene.
AB  - Functional analysis of regulatory elements in the human tissue plasminogen
      activator (tPA) gene showed that its promoter (-119/+169) is activated by UV
      irradiation in HeLa cells. We demonstrated here that the AP-2 like CCCCACCC
      sequence is involved in the UV-mediated activation and Sp1 binds to the sequence.

PMID- 10879490
TI  - Sodium ATPase and sodium/proton antiporter are not obligatory for sodium
      homeostasis of Enterococcus hirae at acid pH.
AB  - Enterococcus hirae grows in a broad pH range from 5 to 11. An E. hirae mutant
      7683 lacking the activities of two sodium pumps, Na+-ATPase and Na+/H+
      antiporter, does not grow in high Na+ medium at pH above 7.5. We found that 7683
      grew normally in high Na+ medium at pH 5.5. Although an energy-dependent sodium
      extrusion at pH 5.5 was missing, the intracellular levels of Na+ and K+ were
      normal in this mutant. The Na+ influx rates of 7683 and two other strains at pH
      5.5 were much slower than those at pH 7.5. These results suggest that Na+
      elimination of this bacterium at acid pH is achieved by a decrease in Na+ entry
      and a normal K+ uptake.

PMID- 10879491
TI  - Malvidin 3-rutinoside as the pigment responsible for bract color in Curcuma
      alismatifolia.
AB  - Malvidin 3-rutinoside was the only anthocyanin identified from pink bracts of
      Curcuma alismatifolia cultivars. The concentration of malvidin 3-rutinoside in
      three cultivars increased as the intensity of the pink color in the bracts
      increased.

PMID- 10879492
TI  - Carotenoids in human blood plasma after ingesting paprika juice.
AB  - We investigated the presence of different carotenoids in male human subject after
      the ingestion of paprika juice, and identified capsanthin, capsanthone,
      cucurbitaxanthin A, 11-cis-capsanthin, lutein and zeaxanthin in the human plasma.
      These results suggest that capsanthone and 11-cis-capsanthin might be as
      important as capsanthin for human health.

PMID- 10879493
TI  - Identification and characterization of a novel gene, hos3+, the function of which
      is necessary for growth under high osmotic stress in fission yeast.
AB  - hos3 mutants of the fission yeast Schizosaccharomyces pombe showed the phenotype
      of high osmolarity sensitivity for growth. An S. pombe strain carrying the hos3
      M26 allele cannot form colonies on agar plates containing 2 M glucose, but the
      parental strain can do so very well, as demonstrated previously. The hos3+ gene
      was cloned and identified as one that encodes a small protein of 94 amino acids,
      which shows no sequence similarity to any other proteins in the current
      databases. A hos3delta strain, which we then constructed, had the phenotype of
      high osmolarity sensitivity, as in the case of the original hos3-M26 mutant. More
      interestingly, when these hos- cells were grown in the non-permissive growth
      condition in the presence of 2 M glucose, we found that unusually many septated
      cells were accumulated after a prolonged incubation. A multicopy suppressor gene
      for hos- mutations was also isolated and identified as the dsk1+ gene encoding a
      protein kinase, which was previously suggested to be implicated in a process of
      the mitotic regulation of S. pombe. The function of the hos3+ gene is discussed
      from these results.

PMID- 10879494
TI  - Processing glucosidase inhibition by 1-azafagomine.
AB  - Natural azasugars have the ring oxygen substituted by nitrogen. They show potent
      inhibitory activity against glycosidases. The effect of substituting the ring
      carbon with nitrogen was examined with 1-azafagomine. 1-Azafagomine exhibited
      similar activity against processing glucosidase to that of fagomine.

PMID- 10879496
TI  - A significant time for Europe

PMID- 10879495
TI  - Identification of a new gene responsible for the oxygen tolerance in aerobic life
      of Streptococcus mutans.
AB  - Alkyl hydroperoxide reductase in Streptococcus mutans consists of two components,
      Nox-1 and AhpC. Deletion of nox-1 and ahpC in a double mutant as well as the wild
      type of Streptococcus mutans can form colonies in the presence of air to the same
      extent. The evidence suggested the presence of some other antioxidant system(s)
      independent of the Nox-1/AhpC system in the bacterium. Here we identified a new
      antioxidant gene (dpr) and the gene product (Dpr) which complements the defect of
      peroxidase activity caused by the deletion of nox-1 and ahpC in S. mutans. The
      dpr-disruption mutant of S. mutans could form colonies anaerobically but not
      aerobically.

PMID- 10879497
TI  - German fraud inquiry casts a wider net of suspicion...as disillusionment reigns
      in task force.

PMID- 10879498
TI  - Hawaii reaches for the stars with astronomy master plan

PMID- 10879499
TI  - Oxford epidemiologist wins apology for promotion slur.

PMID- 10879501
TI  - UK panel calls for more cuts to carbon dioxide emission

PMID- 10879500
TI  - Europe edges closer to an integrated science policy.

PMID- 10879502
TI  - Brookhaven collider opens its quest for Big Bang conditions

PMID- 10879503
TI  - Shares rebound at scent of draft sequence.

PMID- 10879504
TI  - GM food 'dumped on India as aid'.

PMID- 10879505
TI  - A question of trust.

PMID- 10879506
TI  - Leatherback's survival will depend on an international effort.

PMID- 10879507
TI  - Biotech pioneers have duties as well as rights.

PMID- 10879508
TI  - Don't ignore good work that you have to look for.

PMID- 10879509
TI  - Database could give children safer medicines.

PMID- 10879510
TI  - Showman barely blinked at a dose of nerve gas.

PMID- 10879512
TI  - The well-spring

PMID- 10879511
TI  - Japan may seek embryo cells from overseas.

PMID- 10879513
TI  - In the days of the comet

PMID- 10879514
TI  - Neural circuits in silicon.

PMID- 10879515
TI  - Self-repair in the brain.

PMID- 10879516
TI  - Chirality, magnetism and light

PMID- 10879518
TI  - Electrons in artificial atoms

PMID- 10879517
TI  - Genetics. Reverse gear for Drosophila.

PMID- 10879519
TI  - Malaria. A mosquito transformed.

PMID- 10879520
TI  - Kent R. Wilson (1937-2000)

PMID- 10879521
TI  - Whale songs lengthen in response to sonar.

PMID- 10879522
TI  - Antioxidant activity of fresh apples.

PMID- 10879523
TI  - Constraints to growth of boreal forests.

PMID- 10879524
TI  - The genetic legacy of the Quaternary ice ages.
AB  - Global climate has fluctuated greatly during the past three million years,
      leading to the recent major ice ages. An inescapable consequence for most living
      organisms is great changes in their distribution, which are expressed differently
      in boreal, temperate and tropical zones. Such range changes can be expected to
      have genetic consequences, and the advent of DNA technology provides most
      suitable markers to examine these. Several good data sets are now available,
      which provide tests of expectations, insights into species colonization and
      unexpected genetic subdivision and mixture of species. The genetic structure of
      human populations may be viewed in the same context. The present genetic
      structure of populations, species and communities has been mainly formed by
      Quaternary ice ages, and genetic, fossil and physical data combined can greatly
      help our understanding of how organisms were so affected.

PMID- 10879525
TI  - Crystal structure of the bacterial membrane protein TolC central to multidrug
      efflux and protein export.
AB  - Diverse molecules, from small antibacterial drugs to large protein toxins, are
      exported directly across both cell membranes of gram-negative bacteria. This
      export is brought about by the reversible interaction of substrate-specific inner
      membrane proteins with an outer-membrane protein of the TolC family, thus
      bypassing the intervening periplasm. Here we report the 2.1-A crystal structure
      of TolC from Escherichia coli, revealing a distinctive and previously unknown
      fold. Three TolC protomers assemble to form a continuous, solvent-accessible
      conduit--a 'channel-tunnel' over 140 A long that spans both the outer membrane
      and periplasmic space. The periplasmic or proximal end of the tunnel is sealed by
      sets of coiled helices. We suggest these could be untwisted by an allosteric
      mechanism, mediated by protein-protein interactions, to open the tunnel. The
      structure provides an explanation of how the cell cytosol is connected to the
      external environment during export, and suggests a general mechanism for the
      action of bacterial efflux pumps.

PMID- 10879526
TI  - Optical detection of meteoroidal impacts on the Moon
AB  - Impacts of meteoroids on the Moon should cause detectable optical flashes, but
      the population of objects that are big enough is very low, and hitherto no
      unambiguous impact flashes have been recorded. The flux of meteoroids associated
      with the Leonid meteor shower of 18 November 1999 was predicted to produce
      observable flashes on the night side of the Moon. Here we report the unambiguous
      detection of five such impact flashes, three of which were seen simultaneously by
      other observers. We also observed a possible impact flash on 16 July 1999. All of
      the flashes were of very brief duration (<0.02 s), as expected for high-speed
      impacts.

PMID- 10879527
TI  - Hidden symmetries in the energy levels of excitonic 'artificial atoms'
AB  - Quantum dots or 'artificial atoms' are of fundamental and technological interest-
      for example, quantum dots may form the basis of new generations of lasers. The
      emission in quantum-dot lasers originates from the recombination of excitonic
      complexes, so it is important to understand the dot's internal electronic
      structure (and of fundamental interest to compare this to real atomic structure).
      Here we investigate artificial electronic structure by injecting optically a
      controlled number of electrons and holes into an isolated single quantum dot. The
      charge carriers form complexes that are artificial analogues of hydrogen, helium,
      lithium, beryllium, boron and carbon excitonic atoms. We observe that electrons
      and holes occupy the confined electronic shells in characteristic numbers
      according to the Pauli exclusion principle. In each degenerate shell, collective
      condensation of the electrons and holes into coherent many-exciton ground states
      takes place; this phenomenon results from hidden symmetries (the analogue of
      Hund's rules for real atoms) in the energy function that describes the multi
      particle system. Breaking of the hidden symmetries leads to unusual quantum
      interferences in emission involving excited states.

PMID- 10879528
TI  - Optical emission from a charge-tunable quantum ring
AB  - Quantum dots or rings are artificial nanometre-sized clusters that confine
      electrons in all three directions. They can be fabricated in a semiconductor
      system by embedding an island of low-bandgap material in a sea of material with a
      higher bandgap. Quantum dots are often referred to as artificial atoms because,
      when filled sequentially with electrons, the charging energies are pronounced for
      particular electron numbers; this is analogous to Hund's rules in atomic physics.
      But semiconductors also have a valence band with strong optical transitions to
      the conduction band. These transitions are the basis for the application of
      quantum dots as laser emitters, storage devices and fluorescence markers. Here we
      report how the optical emission (photoluminescence) of a single quantum ring
      changes as electrons are added one-by-one. We find that the emission energy
      changes abruptly whenever an electron is added to the artificial atom, and that
      the sizes of the jumps reveal a shell structure.

PMID- 10879529
TI  - Gigantic optical nonlinearity in one-dimensional Mott-Hubbard insulators
AB  - The realization of all-optical switching, modulating and computing devices is an
      important goal in modern optical technology. Nonlinear optical materials with
      large third-order nonlinear susceptibilities (chi(3)) are indispensable for such
      devices, because the magnitude of this quantity dominates the device performance.
      A key strategy in the development of new materials with large nonlinear
      susceptibilities is the exploration of quasi-one-dimensional systems, or 'quantum
      wires'--the quantum confinement of electron-hole motion in one-dimensional space
      can enhance chi(3). Two types of chemically synthesized quantum wires have been
      extensively studied: the band insulators of silicon polymers, and Peierls
      insulators of pi-conjugated polymers and platinum halides. In these systems,
      chi(3) values of 10(-12) to 10(-7) e.s.u. (electrostatic system of units) have
      been reported. Here we demonstrate an anomalous enhancement of the third-order
      nonlinear susceptibility in a different category of quantum wires: one
      dimensional Mott insulators of 3d transition-metal oxides and halides. By
      analysing the electroreflectance spectra of these compounds, we measure chi(3)
      values in the range 10(-8) to 10(-5) e.s.u. The anomalous enhancement results
      from a large dipole moment between the lowest two excited states of these
      systems.

PMID- 10879530
TI  - Enantioselective magnetochiral photochemistry
AB  - Many chemical and physical systems can occur in two forms distinguished solely by
      being mirror images of each other. This phenomenon, known as chirality, is
      important in biochemistry, where reactions involving chiral molecules often
      require the participation of one specific enantiomer (mirror image) of the two
      possible ones. In fact, terrestrial life utilizes only the L enantiomers of amino
      acids, a pattern that is known as the 'homochirality of life' and which has
      stimulated long-standing efforts to understand its origin. Reactions can proceed
      enantioselectively if chiral reactants or catalysts are involved, or if some
      external chiral influence is present. But because chiral reactants and catalysts
      themselves require an enantioselective production process, efforts to understand
      the homochirality of life have focused on external chiral influences. One such
      external influence is circularly polarized light, which can influence the
      chirality of photochemical reaction products. Because natural optical activity,
      which occurs exclusively in media lacking mirror symmetry, and magnetic optical
      activity, which can occur in all media and is induced by longitudinal magnetic
      fields, both cause polarization rotation of light, the potential for magnetically
      induced enantioselectivity in chemical reactions has been investigated, but no
      convincing demonstrations of such an effect have been found. Here we show
      experimentally that magnetochiral anisotropy--an effect linking chirality and
      magnetism--can give rise to an enantiomeric excess in a photochemical reaction
      driven by unpolarized light in a parallel magnetic field, which suggests that
      this effect may have played a role in the origin of the homochirality of life.

PMID- 10879531
TI  - Reduced North Atlantic Deep Water flux to the glacial Southern Ocean inferred
      from neodymium isotope ratios
AB  - The global circulation of the oceans and the atmosphere transports heat around
      the Earth. Broecker and Denton suggested that changes in the global ocean
      circulation might have triggered or enhanced the glacial-interglacial cycles. But
      proxy data for past circulation taken from sediment cores in the South Atlantic
      Ocean have yielded conflicting interpretations of ocean circulation in glacial
      times--delta13C variations in benthic foraminifera support the idea of a glacial
      weakening or shutdown of North Atlantic Deep Water production, whereas other
      proxies, such as Cd/Ca, Ba/Ca and 231Pa/230Th ratios, show little change from the
      Last Glacial Maximum to the Holocene epoch. Here we report neodymium isotope
      ratios from the dispersed Fe-Mn oxide component of two southeast Atlantic
      sediment cores. Both cores show variations that tend towards North Atlantic
      signatures during the warm marine isotope stages 1 and 3, whereas for the full
      glacial stages 2 and 4 they are closer to Pacific Ocean signatures. We conclude
      that the export of North Atlantic Deep Water to the Southern Ocean has resembled
      present-day conditions during the warm climate intervals, but was reduced during
      the cold stages. An increase in biological productivity may explain the various
      proxy data during the times of reduced North Atlantic Deep Water export.

PMID- 10879532
TI  - Mapping the Hawaiian plume conduit with converted seismic waves
AB  - The volcanic edifice of the Hawaiian islands and seamounts, as well as the
      surrounding area of shallow sea floor known as the Hawaiian swell, are believed
      to result from the passage of the oceanic lithosphere over a mantle hotspot.
      Although geochemical and gravity observations indicate the existence of a mantle
      thermal plume beneath Hawaii, no direct seismic evidence for such a plume in the
      upper mantle has yet been found. Here we present an analysis of compressional-to
      shear (P-to-S) converted seismic phases, recorded on seismograph stations on the
      Hawaiian islands, that indicate a zone of very low shear-wave velocity (< 4 km s(
      1)) starting at 130-140 km depth beneath the central part of the island of Hawaii
      and extending deeper into the upper mantle. We also find that the upper-mantle
      transition zone (410-660 km depth) appears to be thinned by up to 40-50 km to the
      south-southwest of the island of Hawaii. We interpret these observations as
      localized effects of the Hawaiian plume conduit in the asthenosphere and mantle
      transition zone with excess temperature of approximately 300 degrees C. Large
      variations in the transition-zone thickness suggest a lower-mantle origin of the
      Hawaiian plume similar to the Iceland plume, but our results indicate a 100
      degrees C higher temperature for the Hawaiian plume.

PMID- 10879533
TI  - A pug-nosed crocodyliform from the Late Cretaceous of Madagascar.
AB  - Although the image of crocodyliforms as 'unchanged living fossils' is naive,
      several morphological features of the group are thought to have varied only
      within narrow limits during the course of evolution. These include an elongate
      snout with an array of conical teeth, a dorsoventrally flattened skull and a
      posteriorly positioned jaw articulation, which provides a powerful bite force.
      Here we report an exquisitely preserved specimen of a new taxon from the Late
      Cretaceous of Madagascar that deviates profoundly from this Bauplan, possessing
      an extremely blunt snout, a tall, rounded skull, an anteriorly shifted jaw joint
      and clove-shaped, multicusped teeth reminiscent of those of some ornithischian
      dinosaurs. This last feature implies that the diet of the new taxon may have been
      predominantly if not exclusively herbivorous. A close relationship with
      notosuchid crocodyliforms, particularly Uruguaysuchus (Late Cretaceous, Uruguay)
      is suggested by several shared derived features; this supports a biogeographical
      hypothesis that Madagascar and South America were linked during the Late
      Cretaceous.

PMID- 10879534
TI  - Diversity and endemism of the benthic seamount fauna in the southwest Pacific.
AB  - Seamounts comprise a unique deep-sea environment, characterized by substantially
      enhanced currents and a fauna that is dominated by suspension feeders, such as
      corals. The potential importance of these steep-sided undersea mountains, which
      are generally of volcanic origin, to ocean biogeography and diversity was
      recognized over 40 years ago, but this environment has remained very poorly
      explored. A review of seamount biota and biogeography reported a total of 597
      invertebrate species recorded from seamounts worldwide since the Challenger
      expedition of 1872. Most reports, based on a single taxonomic group, were
      extremely limited: 5 seamounts of the estimated more than 30,000 seamounts in the
      world's oceans accounted for 72% of the species recorded. Only 15% of the species
      occurring on seamounts were considered potential seamount endemics. Here we
      report the discovery of more than 850 macro- and megafaunal species from
      seamounts in the Tasman Sea and southeast Coral Sea, of which 29-34% are new to
      science and potential seamount endemics. Low species overlap between seamounts in
      different portions of the region indicates that the seamounts in clusters or
      along ridge systems function as 'island groups' or 'chains' leading to highly
      localized species distributions and apparent speciation between groups or ridge
      systems that is exceptional for the deep sea. These results have substantial
      implications for the conservation of this fauna, which is threatened by fishing
      activity.

PMID- 10879535
TI  - Digital selection and analogue amplification coexist in a cortex-inspired silicon
      circuit.
AB  - Digital circuits such as the flip-flop use feedback to achieve multistability and
      nonlinearity to restore signals to logical levels, for example 0 and 1. Analogue
      feedback circuits are generally designed to operate linearly, so that signals are
      over a range, and the response is unique. By contrast, the response of cortical
      circuits to sensory stimulation can be both multistable and graded. We propose
      that the neocortex combines digital selection of an active set of neurons with
      analogue response by dynamically varying the positive feedback inherent in its
      recurrent connections. Strong positive feedback causes differential instabilities
      that drive the selection of a set of active neurons under the constraints
      embedded in the synaptic weights. Once selected, the active neurons generate
      weaker, stable feedback that provides analogue amplification of the input. Here
      we present our model of cortical processing as an electronic circuit that
      emulates this hybrid operation, and so is able to perform computations that are
      similar to stimulus selection, gain modulation and spatiotemporal pattern
      generation in the neocortex.

PMID- 10879536
TI  - Induction of neurogenesis in the neocortex of adult mice.
AB  - Neurogenesis normally only occurs in limited areas of the adult mammalian brain-
      the hippocampus, olfactory bulb and epithelium, and at low levels in some regions
      of macaque cortex. Here we show that endogenous neural precursors can be induced
      in situ to differentiate into mature neurons, in regions of adult mammalian
      neocortex that do not normally undergo any neurogenesis. This differentiation
      occurs in a layer- and region-specific manner, and the neurons can re-form
      appropriate corticothalamic connections. We induced synchronous apoptotic
      degeneration of corticothalamic neurons in layer VI of anterior cortex of adult
      mice and examined the fates of dividing cells within cortex, using markers for
      DNA replication (5-bromodeoxyuridine; BrdU) and progressive neuronal
      differentiation. Newly made, BrdU-positive cells expressed NeuN, a mature
      neuronal marker, in regions of cortex undergoing targeted neuronal death and
      survived for at least 28 weeks. Subsets of BrdU+ precursors expressed
      Doublecortin, a protein found exclusively in migrating neurons, and Hu, an early
      neuronal marker. Retrograde labelling from thalamus demonstrated that BrdU+
      neurons can form long-distance corticothalamic connections. Our results indicate
      that neuronal replacement therapies for neurodegenerative disease and CNS injury
      may be possible through manipulation of endogenous neural precursors in situ.

PMID- 10879537
TI  - Regulation of distinct AMPA receptor phosphorylation sites during bidirectional
      synaptic plasticity.
AB  - Bidirectional changes in the efficacy of neuronal synaptic transmission, such as
      hippocampal long-term potentiation (LTP) and long-term depression (LTD), are
      thought to be mechanisms for information storage in the brain. LTP and LTD may be
      mediated by the modulation of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazloe
      proprionic acid) receptor phosphorylation. Here we show that LTP and LTD
      reversibly modify the phosphorylation of the AMPA receptor GluR1 subunit.
      However, contrary to the hypothesis that LTP and LTD are the functional inverse
      of each other, we find that they are associated with phosphorylation and
      dephosphorylation, respectively, of distinct GluR1 phosphorylation sites.
      Moreover, the site modulated depends on the stimulation history of the synapse.
      LTD induction in naive synapses dephosphorylates the major cyclic-AMP-dependent
      protein kinase (PKA) site, whereas in potentiated synapses the major
      calcium/calmodulin-dependent protein kinase II (CaMKII) site is dephosphorylated.
      Conversely, LTP induction in naive synapses and depressed synapses increases
      phosphorylation of the CaMKII site and the PKA site, respectively. LTP is
      differentially sensitive to CaMKII and PKA inhibitors depending on the history of
      the synapse. These results indicate that AMPA receptor phosphorylation is
      critical for synaptic plasticity, and that identical stimulation conditions
      recruit different signal-transduction pathways depending on synaptic history.

PMID- 10879538
TI  - Stable germline transformation of the malaria mosquito Anopheles stephensi.
AB  - Anopheline mosquito species are obligatory vectors for human malaria, an
      infectious disease that affects hundreds of millions of people living in tropical
      and subtropical countries. The lack of a suitable gene transfer technology for
      these mosquitoes has hampered the molecular genetic analysis of their physiology,
      including the molecular interactions between the vector and the malaria parasite.
      Here we show that a transposon, based on the Minos element and bearing exogenous
      DNA, can integrate efficiently and stably into the germ line of the human malaria
      vector Anopheles stephensi, through a transposase-mediated process.

PMID- 10879539
TI  - A small-molecule nitroimidazopyran drug candidate for the treatment of
      tuberculosis.
AB  - Mycobacterium tuberculosis, which causes tuberculosis, is the greatest single
      infectious cause of mortality worldwide, killing roughly two million people
      annually. Estimates indicate that one-third of the world population is infected
      with latent M. tuberculosis. The synergy between tuberculosis and the AIDS
      epidemic, and the surge of multidrug-resistant clinical isolates of M.
      tuberculosis have reaffirmed tuberculosis as a primary public health threat.
      However, new antitubercular drugs with new mechanisms of action have not been
      developed in over thirty years. Here we report a series of compounds containing a
      nitroimidazopyran nucleus that possess antitubercular activity. After activation
      by a mechanism dependent on M. tuberculosis F420 cofactor, nitroimidazopyrans
      inhibited the synthesis of protein and cell wall lipid. In contrast to current
      antitubercular drugs, nitroimidazopyrans exhibited bactericidal activity against
      both replicating and static M. tuberculosis. Lead compound PA-824 showed potent
      bactericidal activity against multidrugresistant M. tuberculosis and promising
      oral activity in animal infection models. We conclude that nitroimidazopyrans
      offer the practical qualities of a small molecule with the potential for the
      treatment of tuberculosis.

PMID- 10879540
TI  - Embryonic lethality in mice homozygous for a processing-deficient allele of
      Notch1.
AB  - The Notch genes encode single-pass transmembrane receptors that transduce the
      extracellular signals responsible for cell fate determination during several
      steps of metazoan development. The mechanism by which extracellular signals
      affect gene transcription and ultimately cell fate decisions is beginning to
      emerge for the Notch signalling pathway. One paradigm is that ligand binding to
      Notch triggers a Presenilin1-dependent proteolytic release of the Notch
      intracellular domain from the membrane, resulting in low amounts of Notch
      intracellular domain which form a nuclear complex with CBF1/Su(H)/Lag1 to
      activate transcription of downstream targets. Not all observations clearly
      support this processing model, and the most rigorous test of it is to block
      processing in vivo and then determine the ability of unprocessed Notch to signal.
      Here we report that the phenotypes associated with a single point mutation at the
      intramembranous processing site of Notch1, Val1,744-->Gly, resemble the null
      Notch1 phenotype. Our results show that efficient intramembranous processing of
      Notch1 is indispensable for embryonic viability and proper early embryonic
      development in vivo.

PMID- 10879541
TI  - An extracellular activator of the Drosophila JAK/STAT pathway is a sex
      determination signal element.
AB  - Metazoans use diverse and rapidly evolving mechanisms to determine sex. In
      Drosophila melanogaster an X-chromosome-counting mechanism determines the sex of
      an individual by regulating the master switch gene, Sex-lethal (Sxl). The X
      chromosome dose is communicated to Sxl by a set of X-linked signal elements
      (XSEs), which activate transcription of Sxl through its 'establishment' promoter,
      SxlPe. Here we describe a new XSE called sisterlessC (sisC) whose mode of action
      differs from that of previously characterized XSEs, all of which encode
      transcription factors that activate SxlPe directly. In contrast, sisC encodes a
      secreted ligand for the Drosophila Janus kinase (JAK) and 'signal transducer and
      activator of transcription' (STAT) signal transduction pathway and is allelic to
      outstretched (os, also called unpaired). We conclude that sisC works indirectly
      on Sxl through this signalling pathway because mutations in sisC or in the genes
      encoding Drosophila JAK or STAT reduce expression of SxlPe similarly. The
      involvement of os in sex determination confirms that secreted ligands can
      function in cell-autonomous processes. Unlike sex signals for other organisms,
      sisC has acquired its sex-specific function while maintaining non-sex-specific
      roles in development, a characteristic that it shares with all other Drosophila
      XSEs.

PMID- 10879543
TI  - Clinical neurology and executive dysfunction.
AB  - Executive function is a uniquely human ability that permits an individual to
      plan, carry out, and monitor a sequence of actions that is intended to accomplish
      a goal. This crucial neurobehavioral capacity depends on the integrity of the
      frontal lobes, most importantly the dorsolateral prefrontal cortices and their
      connections. Executive dysfunction is associated with a wide range of neurologic
      disorders that affect these regions. In this paper, executive dysfunction is
      considered from the perspective of behavioral neurology, and the lesion method is
      employed to illustrate this impairment in a diverse group of disorders. Frontal
      system damage leading to disturbed executive function is common and clinically
      significant. Recognition of this syndrome is critical for ensuring the correct
      diagnosis, accurate prognosis, and appropriate treatment of affected patients.
      Executive dysfunction also represents an intriguing aspect of brain-behavior
      relationships and offers important insights into one of the highest cerebral
      functions.

PMID- 10879542
TI  - Compromised HOXA5 function can limit p53 expression in human breast tumours.
AB  - Expression of the p53 gene protects cells against malignant transformation.
      Whereas control of p53 degradation has been a subject of intense scrutiny, little
      is known about the factors that regulate p53 synthesis. Here we show that p53
      messenger RNA levels are low in a large proportion of breast tumours. Seeking
      potential regulators of p53 transcription, we found consensus HOX binding sites
      in the p53 promoterS. Transient transfection of Hox/HOXA5 activated the p53
      promoter. Expression of HOXA5 in epithelial cancer cells expressing wild-type
      p53, but not in isogenic variants lacking the p53 gene, led to apoptotic cell
      death. Moreover, breast cancer cell lines and patient tumours display a
      coordinate loss of p53 and HOXA5 mRNA and protein expression. The HOXA5 promoter
      region was methylated in 16 out of 20 p53-negative breast tumour specimens. We
      conclude that loss of expression of p53 in human breast cancer may be primarily
      due to lack of expression of HOXA5.

PMID- 10879544
TI  - Working memory: a foundation for executive abilities and higher-order cognitive
      skills.
AB  - This paper presents a discussion of working memory and the relationship between
      working memory and executive abilities. An overview of three prominent models of
      working memory is provided with experimental support for each. The importance of
      assessing working memory in individuals with brain damage and related language
      disorders is discussed, as well as limitations of the currently available
      assessment tools. Lastly, future directions for the development of both theory
      and assessment tools are offered.

PMID- 10879545
TI  - Cognitive flexibility: theory, assessment, and treatment.
AB  - Cognitive flexibility is often impaired in persons with neurogenic communication
      and cognition disorders. There is, however, little information to guide
      clinicians in assessing and treating this aspect of executive functioning. The
      purpose of this article is to provide a framework for clinicians who evaluate and
      treat persons with impaired cognitive flexibility. It (1) identifies basic
      definitions of flexibility, (2) discusses tests frequently used to assess
      flexibility, (3) provides a profile of characteristic patterns of inflexibility
      that persons with different communication and cognition disorders exhibit, and
      (4) discusses treatment options.

PMID- 10879546
TI  - Assessing and managing unawareness of self.
AB  - Awareness deficits present challenges to recovery and barriers to the
      rehabilitation process. This paper provides a clinical framework for assessing
      and managing awareness deficits. It begins with a review of several theoretical
      and clinical models of awareness in order to identify important characteristics
      of awareness disorders. A variety of methods for measuring awareness are
      reviewed. Questions to guide the assessment process are described along with
      sources for answering the questions. Considerations for implementing three
      different intervention approaches are also detailed. These interventions include
      an Individual Awareness Enhancement Program, Procedural Training and
      Environmental Support, and Caregiver Training and Education. The associated
      awareness literature is reviewed. An actual case study illustrating the
      assessment and intervention approaches is provided at the end of the paper.

PMID- 10879547
TI  - Assessing the executive function abilities of adults with neurogenic
      communication disorders.
AB  - Whereas it is known that executive function abilities are often impaired in
      clients having neurogenic communication disorders, few assessments of this
      cognitive domain are available that consider the speech and language deficits of
      this population. This article provides an overview of current procedures for
      assessing executive functions including a discussion of team approaches to
      assessment, a review of currently available neuropsychological and functional
      tests of executive function abilities, as well as a critique of those assessment
      procedures. In addition, suggestions are provided for how best to use or modify
      appropriately current tests of executive functioning for clients having acquired
      speech and language disorders as a result of brain damage.

PMID- 10879548
TI  - Assessment of executive functions in clinical settings: problems and
      recommendations.
AB  - In this article we provide a tutorial review of various theoretical issues that
      surround executive function research from the perspective of cognitive
      psychology, focusing on issues that have important implications for clinical
      assessment of executive functioning. We first discuss theoretical and clinical
      reasons for the importance of understanding executive functions and then point
      out some serious problems with the common practice of relying exclusively on
      complex neuropsychological tests, such as the Wisconsin Card Sorting Test and the
      Tower of Hanoi, as general measures of executive functioning. We then briefly
      present a recent individual differences study of executive functions conducted in
      our laboratory that attempted to overcome certain limitations associated with the
      more typical approach. On the basis of the theoretical issues discussed and the
      results from our study, we offer some concrete suggestions and recommendations
      for the measurement and assessment of executive functions in clinical settings.

PMID- 10879549
TI  - Results of carotid endarterectomy: the gold standard for carotid repair.
AB  - Carotid endarterectomy (CEA) generated substantial controversy during the mid
      1980s because of the large number of operations that were being performed in the
      United States compared with other industrialized nations, the emergence of
      antiplatelet therapy as a possible alternative to surgical treatment for carotid
      disease, and the lingering question about whether the safety of CEA in published
      reports actually is attained at the thousands of hospitals in which it is
      performed. Several influential randomized trials now have validated the efficacy
      of CEA for stroke prevention in symptomatic patients having at least 50% carotid
      stenosis, as well as in asymptomatic patients with higher-grade lesions and no
      surgical contraindications. It must be remembered, however, that the surgeons who
      participated in these trials were vetted on the basis of acceptable stroke and
      mortality rates that were documented for their previous experience with CEA. A
      number of statewide and Medicare audits have shown that, although the
      complication rates of CEA appear to have declined to some extent during the past
      decade, they still exceed the standards established by the randomized trials in
      many geographic areas and often assume an inverse relationship to the annual
      volume of CEAs performed at hospitals and by individual surgeons. Although the
      indications for CEA never have been more clearly known or widely accepted than
      they are today, its designation as the gold standard for the management of
      patients meeting these criteria continues to depend on outcome assessment and
      quality control at the local level. Furthermore, these measures will be just as
      necessary for carotid balloon angioplasty and intraluminal stenting, because any
      competitive form of treatment legitimately should receive the same scrutiny as
      CEA.

PMID- 10879550
TI  - Diagnosis and treatment of proximal carotid lesions.
AB  - Means for endovascular therapy have radically altered the treatment paradigm for
      occlusive lesions of the aortic arch vessels. Diagnosis of these problems by
      noninvasive means is becoming increasingly more common, allowing invasive
      evaluation and treatment to occur simultaneously. Most of these lesions are
      atherosclerotic and occur at the vessel origin. These types of lesions tend to be
      heavily calcified and unresponsive to simple angioplasty alone. Angioplasty in
      conjunction with stenting offers an additional therapeutic alternative for
      lesions affecting these vessels. A brief review of the alternatives and
      techniques for both open surgical and endovascular treatment of these
      abnormalities will allow the physician caring for patients with these problems to
      offer patients the best treatment option available.

PMID- 10879551
TI  - Carotid endarterectomy versus carotid angioplasty: comparison of current results.
AB  - Carotid endarterectomy is the standard treatment for carotid artery occlusive
      disease, with proven low morbidity and mortality and acceptable long-term
      durability. Recently, enthusiasm for carotid angioplasty and stenting has led to
      increasingly widespread clinical application of this endovascular technique.
      Because no prospective randomized trial has yet been published comparing carotid
      endarterectomy with carotid angioplasty and stenting, we must use data from
      statewide, population-based, and single-center reports to compare the procedures.
      Although carotid stenting has already earned a significant role in treating
      selected patients with carotid disease, current evidence does not indicate the
      use of carotid stenting as a routine alternative to carotid endarterectomy.

PMID- 10879552
TI  - Techniques of carotid artery stenting: the state of the art.
AB  - The technique of carotid stenting has undergone significant refinement since its
      introduction and continues to improve as experience with the procedure matures
      and more suitable equipment becomes available. Improved stent designs and the
      utilization of cerebral protection devices are expected to significantly impact
      on the technique, its ultimate outcomes, and widespread application. In using the
      currently available technology for carotid stenting, patient selection and
      meticulous attention to procedural details are very important in minimizing
      embolic events. In this article, we provide a comprehensive practical discussion
      of the state-of-the-art carotid stenting techniques that have allowed us to
      maintain low event rates.

PMID- 10879553
TI  - Intermediate outcome after carotid stenting: what should we expect?
AB  - Atherosclerosis of the extracranial carotid artery is a major public health
      burden. Stroke is the third leading cause of death in Western countries, after
      heart disease and cancer, and the leading cause of long-term disability. In the
      United States, there are more than 500,000 strokes annually, accounting for
      approximately 3 million stroke survivors with varying degrees of disability. Data
      from stroke registries suggest that internal carotid artery atheroembolic disease
      accounts for approximately 35% of all ischemic cerebral infarctions; therefore,
      approximately 150,000 strokes in the United States per year may be ascribed to
      carotid disease. Surgical endarterectomy has been shown to be superior to medical
      management in the management of severe carotid stenosis in both symptomatic and
      asymptomatic patients. Indeed, carotid endarterectomy has been one of the most
      heavily scrutinized operations over the past 40 years, and newer methods of
      revascularization are being actively explored. With the great technological
      advances in the endovascular treatment of both peripheral and coronary
      atherosclerotic disease, many of these techniques are now being applied to the
      extracranial circulation. We explore the rapidly expanding field of carotid
      artery angioplasty and stenting. The upcoming prospective randomized clinical
      trials of surgical endarterectomy versus carotid angioplasty and stenting also
      are reviewed.

PMID- 10879554
TI  - CREST (Carotid Revascularization Endarterectomy versus Stent Trial): background,
      design, and current status.
AB  - The Carotid Revascularization Endarterectomy versus Stent Trial (CREST) contrasts
      the relative efficacy of carotid endarterectomy (CEA) and carotid angioplasty
      stent (CAS) in preventing primary outcomes of stroke, myocardial infarction, or
      death during a 30-day periprocedural period, or ipsilateral stroke over the
      follow-up period extending up to 4 years. Stroke events will be verified by an
      Adjudication Committee masked to the assigned treatment. The primary eligibility
      criterion is a significant (> or =50%) stenosis of the carotid artery in patients
      with transient ischemic attack or ipsilateral nondisabling stroke within the
      prior 180 days. Men and women will be eligible for the trial, but patients with
      medical conditions likely to limit their participation during the follow-up or to
      interfere with outcome evaluation will be excluded. After a credentialing and
      training phase, 2,500 patients will be randomized to the treatments. Statistical
      analysis of the primary outcome will employ standard survival techniques and will
      result in 90% power to detect annual differences between groups of 1.2% or higher
      in event rates of the primary outcomes.

PMID- 10879555
TI  - Carotid stenting with and without protection devices: should protection be used
      in all patients?
AB  - Embolic events that result in neurological deficits have been the most
      significant concern regarding carotid bifurcation stenting. Ex vivo carotid
      angioplasty studies using human carotid plaques have shown that embolic particles
      were released from all specimens. In addition, transcranial Doppler studies have
      confirmed the presence of multiple emboli in the middle cerebral artery during
      carotid stenting. Preliminary experience with the use of brain protection devices
      for carotid stenting have shown encouraging results in terms of safety and
      efficacy. Moreover, embolic particles have been recovered from all cases in which
      protection devices have been used. We provide the rationale for routine use of
      these protection devices and also review the various protection devices on the
      horizon.

PMID- 10879556
TI  - Nonatherosclerotic arterial disease of the extracranial cerebrovasculature.
AB  - Extracranial carotid and vertebral arterial disease is most often attributable to
      underlying atherosclerosis. However, several other diseases may mimic
      atherosclerosis clinically. These include Takayasu's arteritis, giant cell
      arteritis, fibromuscular dysplasia, dissections, and aneurysms. It is important
      to recognize distinguishing characteristics of each condition to determine the
      appropriate course of treatment and long-term prognosis.

PMID- 10879557
TI  - A novel microbial interaction: obligate commensalism between a new gram-negative
      thermophile and a thermophilic Bacillus strain.
AB  - Obligately commensal interaction between a new gram-negative thermophile and a
      thermophilic Bacillus strain was investigated. From compost samples, a mixed
      culture showing tyrosine phenol-lyase activity was enriched at 60 degrees C. The
      mixed culture consisted of a thermophilic gram-negative strain, SC-1, and a gram
      positive spore-forming strain, SK-1. In mixed cultures, strain SC-1 started to
      grow only when strain SK-1 entered the stationary phase. Although strain SC-1
      showed tyrosine phenol lyase activity, we could not isolate a colony with any
      nutrient medium. For the isolation and cultivation of strain SC-1, we added
      culture supernatant and cell extract of the mixed culture to the basal medium.
      The supernatant and cell extract of the mixed culture contained heat-stable and
      heat-labile factors, respectively, that are essential to the growth of strain SC
      1. During pure cultures of strain SK-1, the heat-stable growth factors were
      released during the growth phase and the heat-labile growth factors were produced
      intracellularly at the early stationary phase. Strain SC-1 was gram-negative and
      microaerophilic, and grows optimally at 60 degrees C. Based on these results, we
      propose a novel commensal interaction between a new gram-negative thermophile,
      strain SC-1, and Bacillus sp. strain SK-1.

PMID- 10879558
TI  - Xylanase from the psychrophilic yeast Cryptococcus adeliae.
AB  - A xylanase belonging to family 10 is produced by Cryptococcus adeliae, an
      Antarctic yeast that exhibits optimal growth at low temperature. The mature
      glycosylated xylanase secreted by C. adeliae is composed of 338 amino acid
      residues and 26 +/- 3 osidic residues, and shares 84% identity with its
      mesophilic counterpart from C. albidus. The xylanase from C. adeliae is less
      thermostable than its mesophilic homologue when the residual activities are
      compared, and this difference was confirmed by differential scanning calorimetry
      experiments. In the range 0 degrees-20 degrees C, the cold-adapted xylanase
      displays a lower activation energy and a higher catalytic efficiency. All these
      observations suggest a less compact, more flexible molecular structure. Analysis
      of computerized molecular models built up for both psychrophilic and mesophilic
      xylanases indicates that the adaptation to cold consists of discrete changes in
      the tridimensional structure: of 53 substitutions, 22 are presumably involved in
      the adaptation process. These changes lead mainly to a less compact hydrophobic
      packing, to the loss of one salt bridge, and to a destabilization of the
      macrodipoles of the helices.

PMID- 10879559
TI  - An obligate methylotrophic, methane-oxidizing Methylomicrobium species from a
      highly alkaline environment.
AB  - A new, obligately methylotrophic, methane-oxidizing bacterium, strain AMO 1, was
      isolated from a mixed sample of sediments from five highly alkaline soda lakes
      (Kenya). Based on its cell ultrastructure and high activity of the hexulose-6
      phosphate synthase, the new isolate belongs to the type I methanotrophs. It
      differed, however, from the known neutrophilic methanotrophs by the ability to
      grow and oxidize methane at high pH values. The bacterium grew optimally with
      methane at pH 9-10. The oxidation of methane, methanol, and formaldehyde was
      optimal at pH 10, and cells were still active up to pH 11. AMO 1 was able to
      oxidize ammonia to nitrite at high pH. A maximal production of nitrite from
      ammonia in batch cultures at pH 10 was observed with 10% of CH4 in the gas phase
      when nitrate was present as nitrogen source. Washed cells of AMO 1 oxidized
      ammonia most actively at pH 10-10.5 in the presence of limiting amounts of
      methanol or CH4. The bacterium was also capable of oxidizing organic sulfur
      compounds at high pH. Washed cells grown with methane exhibited high activity of
      CS2 oxidation and low, but detectable, levels of DMS and DMDS oxidation. The GC
      content of AMO 1 was 50.9mol%. It showed only weak DNA homology with the
      previously described alkaliphilic methanotroph "Methylobacter alcaliphilus"
      strain 20Z and with the neutrophilic species of the genera Methylobacter and
      Methylomonas. According to the 16S rRNA gene sequence analysis, strain AMO 1 was
      most closely related to a neutrophilic methanotroph, Methylomicrobium pelagicum
      (98.2% sequence similarity), within the gamma-Proteobacteria.

PMID- 10879560
TI  - Activity and stability of hyperthermophilic enzymes: a comparative study on two
      archaeal beta-glycosidases.
AB  - S beta gly and CelB are well-studied hyperthermophilic glycosyl hydrolases,
      isolated from the Archaea Sulfolobus solfataricus and Pyrococcus furiosus,
      respectively. Previous studies revealed that the two enzymes are phylogenetically
      related; they are very active and stable at high temperatures, and their overall
      three-dimensional structure is very well conserved. To acquire insight in the
      molecular determinants of thermostability and thermoactivity of these enzymes, we
      have performed a detailed comparison, under identical conditions, of
      enzymological and biochemical parameters of S beta gly and CelB, and we have
      probed the basis of their stability by perturbations induced by temperature, pH,
      ionic strength, and detergents. The major result of the present study is that,
      although the two enzymes are remarkably similar with respect to kinetic
      parameters, substrate specificity, and reaction mechanism, they are strikingly
      different in stability to the different physical or chemical perturbations
      induced. These results provide useful information for the design of further
      experiments aimed at understanding the structure-function relationships in these
      enzymes.

PMID- 10879561
TI  - Low-temperature recovery strategies for the isolation of bacteria from ancient
      permafrost sediments.
AB  - Permafrost represents a unique ecosystem that has allowed the prolonged survival
      of certain bacterial lineages at subzero temperatures. To better understand the
      permafrost microbial community, it is important to identify isolation protocols
      that optimize the recovery of genetically diverse bacterial lineages. We have
      investigated the impact of different low-temperature isolation protocols on
      recovery of aerobic bacteria from northeast Siberian permafrost of variable
      geologic origin and frozen for 5000 to 3 million years. Low-nutrient media
      enhanced the quantitative recovery of bacteria, whereas the isolation of diverse
      morphotypes was maximized on rich media. Cold enrichments done directly in
      natural, undisturbed permafrost led not only to recovery of increased numbers of
      bacteria but also to isolation of genotypes not recovered by means of liquid low
      temperature enrichments. On the other hand, direct plating and growth at 4
      degrees C also led to recovery of diverse genotypes, some of which were not
      recovered following enrichment. Strains recovered from different permafrost
      samples were predominantly oligotrophic and non-spore-forming but were otherwise
      variable from each other in terms of a number of bacteriological characteristics.
      Our data suggest that a combination of isolation protocols from different
      permafrost samples should be used to establish a culture-based survey of the
      different bacterial lineages in permafrost.

PMID- 10879562
TI  - Two different and highly organized mechanisms of translation initiation in the
      archaeon Sulfolobus solfataricus.
AB  - The translational starts of 144 Sulfolobus solfataricus genes have been
      determined by database comparison. Half the genes lie inside operons and the
      other half are at the start of an operon or single genes. A Shine-Dalgarno
      sequence is found upstream of the genes inside operons, but not for the first
      gene in an operon or isolated genes; this indicates that two different mechanisms
      are used for translation initiation in S. solfataricus. A box A transcriptional
      signal is found for the genes starting an operon or isolated genes, but not for
      the genes inside an operon. The box A signal is located about 27 nt upstream of
      the start codon, which implies that little or no upstream sequence is available
      for translation initiation for this group of genes. This finding is discussed.

PMID- 10879563
TI  - Extracellular protease of Natrialba magadii: purification and biochemical
      characterization.
AB  - A serine protease secreted by the haloalkaliphilic archaeon Natrialba magadii at
      the end of the exponential growth phase was isolated. This enzyme was purified 83
      fold with a total yield of 25% by ethanol precipitation, affinity chromatography,
      and gel filtration. The native molecular mass of the enzyme determined by gel
      filtration was 45 kDa. Na. magadii extracellular protease was dependent on high
      salt concentrations for activity and stability, and it had an optimum temperature
      of 60 degrees C in the presence of 1.5M NaCl. The enzyme was stable and had a
      broad pH profile (6-12) with an optimum pH of 8-10 for azocasein hydrolysis. The
      protease was strongly inhibited by diisopropyl fluorophosphate (DFP),
      phenylmethyl sulfonylfluoride (PMSF), and chymostatin, indicating that it is a
      serine protease. It was sensitive to denaturing agents such as SDS, urea, and
      guanidine HCl and activated by thiol-containing reducing agents such as
      dithiotreitol (DTT) and 2-mercaptoethanol. This protease degraded casein and
      gelatin and showed substrate specificity for synthetic peptides containing Phe,
      Tyr, and Leu at the carboxyl terminus, showing that it has chymotrypsin-like
      activity. Na. magadii protease presented no cross-reactivity with polyclonal
      antibodies raised against the extracellular protease of Natronococcus occultus,
      suggesting that although these proteases share several biochemical traits, they
      might be antigenically unrelated.

PMID- 10879564
TI  - "Chance makes a football of man's life".

PMID- 10879565
TI  - How to survey nosocomial infections.
AB  - Many surveillance methods for nosocomial infections (NIs) have been put forward
      in the literature, and all have their advantages and disadvantages. Different
      surveillance methods are useful, depending on whether the objective of
      surveillance is only to increase sensitivity to infection control problems and to
      identify areas with possible infection control problems; to confirm a possible
      infection control problem through comparison with other units or departments; or
      to use surveillance data for identifying the sources of infections. Furthermore,
      time effectiveness is a major point in selecting the most appropriate method,
      particularly the method for case identification. In units or departments with a
      high level of NI, even highly time-consuming surveillance methods may be
      ultimately time-effective; in units or departments with a lower level of NI, the
      time-effectiveness depends on the time necessary for case identification. Close
      liaison with staff in the units is a sine qua non for the success of all
      surveillance activities.

PMID- 10879566
TI  - Scheduled replacement of central venous catheters is not necessary.
AB  - Although half of intensivists routinely replace their central venous catheters
      (CVCs), this practice is not supported by data from randomized control studies or
      by pathophysiology of CVC infection. The daily risk of CVC infection is
      considered to be a constant; the risk of catheter infection is directly related
      to the duration of catheter insertion. Consequently, the routine change of the
      catheter is able to decrease the number of infections per catheter but not to
      modify the number of infections per day of catheter insertion. This assertion is
      supported by evidence-based medicine: scheduled replacement every 3 or 7 days has
      not been shown to alter the infectious risks of CVCs in randomized studies or a
      meta-analysis. Moreover, routine replacement at a new site exposes the patient to
      an increased risk of mechanical complications. The overall rate of mechanical
      complications per catheter inserted is approximately 3%. Guidewire exchange of
      the catheters may reduce the risk of mechanical complications, but unfortunately
      is associated with a higher rate of catheter colonization and catheter-related
      bacteremia. Routine replacement of CVCs is not necessary.

PMID- 10879567
TI  - The clinical and economic consequences of nosocomial central venous catheter
      related infection: are antimicrobial catheters useful?
AB  - Central venous catheters (CVCs) are essential for many hospitalized patients, but
      they are associated with important infectious complications. Recent studies have
      indicated that CVCs coated with antimicrobial agents reduce the incidence of
      catheter-related bloodstream infection (CR BSI). To estimate the clinical and
      economic consequences of short-term central venous catheter-related infection and
      the potential usefulness of antimicrobial-coated catheters, we reviewed and
      synthesized the available relevant literature. Statistical pooling was used to
      estimate the incidence of both catheter colonization and CR BSI. The attributable
      mortality of CR BSI was also evaluated. In addition, the economic consequences of
      both local and systemic catheter-related infection was estimated from literature
      reports that used micro-costing and other techniques. Among patients in whom
      standard, noncoated CVCs are in place for an average of 8 days, 24.7% are
      expected to develop catheter colonization (95% confidence interval [CI(95)],
      22.0%-27.5%). Approximately 5.2% (CI(95), 3.9%-6.5%) will develop CR BSI. The
      attributable mortality of CR BSI remains unclear, but recent studies are
      consistent with a range from 4% to 20%. An episode of local catheter-related
      infection leads to an additional cost of approximately $400, whereas the
      additional cost of CR BSI ranges from approximately $6,005 to $9,738. Formal
      economic analyses indicate that CVCs coated with antibacterial agents (such as
      chlorhexidine-silver sulfadiazine or minocycline-rifampin) likely reduce
      infectious complications, yielding economic advantages. In light of the
      substantial clinical and economic burden of catheter-related infection, hospital
      personnel should adopt proven cost-effective methods to reduce this common and
      important nosocomial complication.

PMID- 10879568
TI  - Improving compliance with hand hygiene in hospitals.
AB  - Hand hygiene prevents cross-infection in hospitals, but compliance with
      recommended instructions often is poor among healthcare workers. Although some
      previous interventions to improve compliance have been successful, none has
      achieved lasting improvement. This article reviews reported barriers to
      appropriate hand hygiene and factors associated with poor compliance. Easy access
      to hand hygiene in a timely fashion and the availability of skin-care lotion both
      appear to be necessary prerequisites for appropriate hand-hygiene behavior. In
      particular, in high-demand situations, hand rub with an alcohol-based solution
      appears to be the only alternative that allows a decent compliance. The hand
      hygiene compliance level does not rely on individual factors alone, and the same
      can be said for its promotion. Because of the complexity of the process of
      change, it is not surprising that solo interventions often fail, and multimodal,
      multidisciplinary strategies are necessary. A framework that includes parameters
      to be considered for hand-hygiene promotion is proposed, based on
      epidemiologically driven evidence and review of the current knowledge. Strategies
      for promotion in hospitals should include reasons for noncompliance with
      recommendations at individual, group, and institutional levels. Potential tools
      for change should address each of these elements and consider their
      interactivity.

PMID- 10879569
TI  - Control of antibiotic use in the community: the Danish experience.
AB  - The selection pressure for antibacterial resistance in the community might not be
      as high as in hospitals. However, it is generally accepted that it is in the
      primary healthcare sector that one can achieve the greatest decrease in the total
      use of antimicrobials. There are significant differences in the overall use of
      antimicrobials among European countries. On average, 80% to 90% of the total
      antibiotic use in each country takes place in the primary healthcare sector.
      Surveillance of the use of antimicrobials is the core for planning interventions
      and monitoring their effect. These interventions may be implemented for either
      political, economic, or professional reasons. Often, but not always, political
      interventions are governmental, and professional interventions are
      recommendations from professional associations. Examples of interventions at
      different levels in the Danish healthcare system, from the general practitioner
      to legislation by the government, will be presented together with their effect on
      the use of antimicrobials.

PMID- 10879570
TI  - Potential dissemination of antibiotic resistance genes from transgenic plants to
      microorganisms.
AB  - Evidence that genes were transferred during evolution from plants to bacteria was
      obtained from nucleotide and protein sequence analyses. However, the extent of
      such transfers among phylogenetically distant organisms is limited by various
      factors, including those related to complexity of the environment and those
      endogenous to the bacteria, designed to prevent a drift of the genome integrity.
      The goal of this article is to give an overview of the potentials and limits of
      natural interkingdom gene transfers, with a particular focus on prokaryote
      originating sequences fitting the nuclear genome of transgenic plants.

PMID- 10879571
TI  - Antibiotic use in developing countries.
AB  - Antimicrobials have been used successfully for over 6 decades, but genes
      expressing resistance to them have emerged in strains of bacteria and have
      disseminated through the global ecosystem to reach infecting microorganisms,
      produce disease, and seriously interfere with therapy, allowing infections to
      progress and kill despite antibiotic administration. The upsurge in prevalence of
      such resistance genes in the bacterial population that colonize and infect humans
      involves two processes, emergence and dissemination, in both of which there have
      been contributions from the developing world, where resistance is common and
      increasing. The emergence of pneumococcal isolates noted in Papua New Guinea and
      later in South Africa that 1 decade later spread to most of the world and the
      intercontinental spread between the United States and Venezuela of a new
      gentamicin resistance gene carried on an epidemic plasmid are examples of the
      ability of bacteria to travel freely, without regard to borders. Complex societal
      issues such as the misuse of antibiotics by physicians, pharmacists, and the
      public; the suboptimal quality of the drugs (emergence); and conditions such as
      crowding, lack of hygiene, poor or nonexistent hospital infection control
      practices, or insufficient surveillance (dissemination) play a largely unmeasured
      role that requires study and solutions. In the meantime, we may intervene to
      delay the emergence of resistance and to limit its spread by promoting the
      judicious use of antibiotics both at the local level as well as from
      multinational organized cooperative efforts. Education and improvement of
      surveillance and socioeconomic conditions are integral parts of any solution
      strategy.

PMID- 10879572
TI  - Methicillin-resistant Staphylococcus aureus in the community: new battlefronts,
      or are the battles lost?
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of
      nosocomial infections worldwide. Interpretation of community MRSA trends is
      problematical, in that the term is ill-defined, and related data are difficult to
      put into context. There are four relevant battlefronts, all of interest to risk
      assessment and prevention. These comprise the following: the issues relating to
      an increasing pool of patients with MRSA discharged from hospitals into the
      community; MRSA spreading to patients in nursing and residential homes; and MRSA
      spreading from patients and healthcare workers to others in the community. There
      are often difficulties in determining whether the fourth issue, MRSA arising
      apparently de novo in the community, is in fact due to one of these other fronts.
      All these battlefronts are important and not yet lost. However, we must agree on
      definitions and design-appropriate surveillance strategies, so that we can best
      inform prevention and control activities to contain these emerged or emerging
      problems.

PMID- 10879573
TI  - Toward new biomaterials.
AB  - Polymers are widely used for a large range of medical devices used as
      biomaterials on a temporary, intermittent, and long-term basis. It is now well
      accepted that the initial rapid adsorption of proteins to polymeric surfaces
      affects the performance of these biomaterials. However, protein adsorption to a
      polymer surface can be modulated by an appropriate design of the interface.
      Extensive study has shown that these interactions can be minimized by coating
      with a highly hydrated layer (hydrogel), by grafting on the surface different
      biomolecules, or by creating domains with chemical functions (charges,
      hydrophilic groups). Our laboratory has investigated the latter approach over the
      past 2 decades, in particular the synthesis and the biological activities of
      polymers to improve the biocompatibility of blood-contacting devices. These
      soluble and insoluble polymers were obtained by chemical substitution of
      macromolecular chains with suitable groups able to develop specific interactions
      with biological components. Applied to compatibility with the blood and the
      immune systems, this concept has been extended to interactions of polymeric
      biomaterials with eukaryotic and prokaryotic cells. The design of new
      biomaterials with low bacterial attachment is thus under intensive study. After a
      brief overview of current trends in the surface modifications of biocompatible
      materials, we will describe how biospecific polymers can be obtained and review
      our recent results on the inhibition of bacterial adhesion using one type of
      functionalized polymer obtained by random substitution. This strategy, applied to
      existing or new materials, seems promising for the limitation of biomaterial
      associated infections.

PMID- 10879575
TI  - Multidose vial transmits HCV.

PMID- 10879574
TI  - Reasons for noncompliance with infection control guidelines.
AB  - Concern frequently is voiced about individuals not complying with guidelines
      intended to prevent spread of antibiotic-resistant pathogens from patient to
      patient, but institutional decisions to ignore Centers for Disease Control and
      Prevention guidelines recommending detection and isolation of colonized patients
      also have contributed greatly to the increasing rate of infections due to these
      pathogens. This is so because colonized patients are the main reservoir for
      spread, and barrier precautions prevent spread much more effectively than
      Standard Precautions. Providing effective leadership and changing this culture of
      noncompliance must begin with the infection control team believing that spread is
      both important and preventable.

PMID- 10879576
TI  - Influences of socioeconomic status, social network, and competence on subjective
      well-being in later life: a meta-analysis.
AB  - Meta-analysis is used to synthesize findings from 286 empirical studies on the
      association of socioeconomic status (SES), social network, and competence with
      subjective well-being (SWB) in the elderly. All three aspects of life
      circumstances are positively associated with SWB. Income is correlated more
      strongly with well-being than is education. The quality of social contacts shows
      stronger associations with SWB than does the quantity of social contacts. Whereas
      having contact with friends is more strongly related to SWB than having contact
      with adult children, there are higher associations between life satisfaction and
      quality of contact with adult children when compared with quality of friendships.
      Moderating influences of gender and age on the effects of SES, social network,
      and competence on SWB are also investigated.

PMID- 10879577
TI  - Factors influencing word naming in younger and older adults.
AB  - The present study examined age differences in the influence of 3 factors that
      previous research has shown to influence word-naming performance. The influence
      of word frequency, orthographic length, and orthographic neighborhood measures
      was examined using large-scale regression analyses on the naming latencies for
      2,820 words. Thirty-one younger adults and 29 older adults named all of these
      words, and age differences in the influence of these factors were examined. The
      results revealed that all 3 factors predicted reliable amounts of variance in
      word-naming latencies for both groups. However, older adults showed a larger
      influence of word frequency and reduced influences of orthographic length and
      orthographic neighborhood density compared with younger adults. Overall, these
      results suggest that lexical level factors increase in influence in older adults
      whereas sublexical factors decrease in influence.

PMID- 10879578
TI  - Psychological treatment of secondary insomnia.
AB  - Psychological treatment of insomnia has focused on primary insomnia (i.e., having
      a psychological origin). Secondary insomnia, sleep disturbance caused by a
      psychiatric or medical disorder, although it is more common than primary
      insomnia, has received very little attention as a result of the belief that it
      would be refractory to treatment. The present study randomly assigned older
      adults with secondary insomnia to a treatment group, 4 sessions composed of
      relaxation and stimulus control, or a no-treatment control group. Self-report
      assessments conducted at pretreatment, posttreatment, and a 3-month follow-up
      revealed that treated participants showed significantly greater improvement on
      wake time during the night, sleep efficiency percentage, and sleep quality
      rating. The authors hypothesize that treatment success was probably due in part
      to difficulty in diagnostic discrimination between primary and secondary
      insomnia.

PMID- 10879579
TI  - Age-related differences in collision detection during deceleration.
AB  - Observers were presented with displays simulating a 3-D environment with
      obstacles in the path of motion. During the trial, observer motion decelerated at
      a constant rate and was followed by a blackout prior to the end of the display.
      On some trials the rate of deceleration resulted in stopping before the
      collision, whereas on other trials the rate of deceleration resulted in a
      collision with the obstacles. The observer's task was to detect which trials
      simulated an impending collision. Proportion of collision judgments was greater
      for older as compared with younger observers when a collision was not simulated.
      Older observers showed less sensitivity to detect collisions than younger
      observers did, particularly at high speeds. The age-dependent results are
      discussed in terms of analyses based on tau and constant deceleration. The
      results suggest that increased accident rates for older drivers may be due to an
      inability to detect collisions at high speeds.

PMID- 10879580
TI  - How aging affects the reading of words in noisy backgrounds.
AB  - Young and old adults were shown simple sentences masked by visual noise. In half
      of the sentences, the final word was predictable; in the other half, it was not.
      The older participants were able to identify the same number of final words as
      the younger ones only when the intensity of the visual noise was significantly
      diminished. However, the difference in the number of correct identifications
      between predictable and unpredictable conditions was higher for the older
      observers than for the younger observers, indicating that older observers benefit
      from context more.

PMID- 10879581
TI  - Negative and positive health effects of caring for a disabled spouse:
      longitudinal findings from the caregiver health effects study.
AB  - Data from the first 2 waves of the Caregiver Health Effects Study (n = 680) were
      analyzed to examine the effects of changes in caregiving involvement on changes
      in caregiver health-related outcomes in a population-based sample of elders
      caring for a disabled spouse. Caregiving involvement was indexed by levels of (a)
      spouse physical impairment, (b) help provided to the spouse, and (c) strain
      associated with providing help. Health-related outcomes included perceived
      health, health-risk behaviors, anxiety symptoms, and depression symptoms.
      Increases in spouse impairment and caregiver strain were generally related to
      poorer outcomes over time (poorer perceived health, increased health-risk
      behaviors, and increased anxiety and depression), whereas increased helping was
      related to better outcomes (decreased anxiety and depression). Results suggest
      that caring for a disabled spouse is a complex phenomenon that can have both
      deleterious and beneficial consequences.

PMID- 10879582
TI  - Evaluations by staff, residents, and community seniors of patronizing speech in
      the nursing home: impact of passive, assertive, or humorous responses.
AB  - Two studies tested the impact of alternative communication in accommodation
      strategies. Nursing home staff and residents (and community-residing seniors in
      Study 2) rated nurse-resident conversational scenarios in which a resident
      responded passively, directly assertively, or humorously (indirectly assertively)
      to a patronizing nurse. The nurse then either maintained a patronizing manner or
      accommodated with a more respectful speech style. Even though all groups devalued
      the nurse who maintained a patronizing speech style, nursing home residents
      predictably showed the most acceptance. The directly assertive response by the
      resident elicited more devaluation of the nonaccommodating nurse than did either
      passive or humorous responses, but also the least favorable ratings of the
      resident. Ratings of the humorous response in Study 2 suggested that humor could
      be a good compromise response style for allowing the receiver of patronizing
      speech to express opposition to a request, yet still maintain an appearance of
      competence and politeness.

PMID- 10879583
TI  - Age-related effects in the marking of old objects in visual search.
AB  - Two studies were performed to examine potential age-related differences in visual
      marking. Visual marking is a limited capacity process that enhances visual search
      through the inhibition of old objects. In Experiment 1, young and old adults
      performed three different search conditions: a full-element baseline, a half
      element baseline, and a gap condition in which they searched through displays
      similar to the full-element baseline condition but with half of the letters
      presented before and the other half of the letters and the target presented after
      a 1000-ms gap. Both old and young adults displayed search slopes in the gap
      condition that were equivalent to slopes obtained in the half-element condition,
      suggesting that they were able to successfully inhibit the old letters. In
      Experiment 2, old and young adults also performed in three different visual
      search conditions but in this case with targets defined either by a form
      difference or by a conjunction of form and color. Both old and young adults
      showed a reduced slope in the gap as compared to the conjunction condition,
      suggesting inhibition of the old objects. The data are discussed in terms of age
      related differences in the top-down control of attention in visual search.

PMID- 10879584
TI  - Experience-based attenuation of age-related differences in music cognition tasks.
AB  - Pianists of a wide experience and age range were tested on measures of musical
      memory and musical perceptual speed to better understand the effects of
      experience on age-cognition relations. Experience-related attenuation might be in
      the form of an Age x Experience interaction or in the form of a "confounding" of
      age and experience such that positive age-experience relations offset negative
      age-cognition relations. It was predicted that the former, considered evidence
      for disuse interpretations of aging, would be likely to emerge in tasks with
      strong experience effects and strong age-related declines among inexperienced
      individuals. However, in no case were the interactions of age and experience on
      the memory or perceptual speed variables significant. There was, however,
      evidence that high levels of experience in the older participants partially
      attenuated the negative effects of age on the memory and perceptual speed tasks.

PMID- 10879585
TI  - Auditory habituation in young and older adults: the verbal transformation effect.
AB  - In 3 experiments, auditory massed repetition was used to examine age-related
      differences in habituation by means of the verbal transformation paradigm.
      Participants heard 10 words (5 high frequency and 5 low frequency), each
      presented 180 times, and they reported perceived changes in the repeated words
      (verbal transformations). In these experiments, older adults reported fewer
      illusory percepts than young adults. Older adults' loss of auditory acuity and
      slowing of processing, stimulus degradation (in young adults), and instructions
      biasing the report of these illusory percepts did not account for the fewer
      illusory percepts reported by the older adults. These findings suggest that older
      adults' reduced susceptibility to habituation arises from centrally located
      declines in the transmission of information within the word-recognition pathway.
      The discussion focuses on the implications that these age-related declines may
      have on word identification during on-line speech perception.

PMID- 10879586
TI  - Comparing the effects of aging and background noise on short-term memory
      performance.
AB  - Paired associate recall was tested as a function of serial position for younger
      and older adults for five word pairs presented aurally in quiet and in noise. In
      Experiment 1, the addition of noise adversely affected recall in young adults,
      but only in the early serial positions. Experiments 2 and 3 suggested that the
      recall of older adults listening to the words in quiet was nearly equivalent to
      that of younger adults listening in noise. In Experiment 4, we determined the
      signal-to-noise ratio (S/N) such that, on average, younger and older adults were
      able to correctly hear the same percentage of words when words were presented one
      at a time in noise. In Experiment 5, younger adults were tested under this S/N.
      Compared with older adults from Experiment 3, younger adults in this experiment
      recalled more words at all serial positions. The results are interpreted as
      showing that encoding in secondary memory is impaired by aging and noise either
      as a function of degraded sensory representations, or as a function of reduced
      processing resources.

PMID- 10879587
TI  - Understanding unfamiliar words: the influence of processing resources, vocabulary
      knowledge, and age.
AB  - In a 2-experiment design, the authors assessed the role of age and ability in
      defining unfamiliar words from context. In Experiment 1, 60 adults aged 18-33 and
      60 adults aged 61-96 read passages with cues to the meaning of rare words, then
      defined them. Older adults produced fewer components of the words' meanings and
      were more likely to produce generalized interpretations of the precise meaning.
      In Experiment 2, 726 adults aged 30-97 selected definitions from 4 choices: the
      exact definition, a generalized interpretation of the exact definition, a
      generalized interpretation of the story, and definition-irrelevant information
      from the story. Adults over age 75 selected fewer precise definitions and more
      generalized interpretations of the story than younger ones. Findings suggest that
      older adults may have special difficulties in deriving the meaning of unfamiliar
      words from context.

PMID- 10879588
TI  - Developmental paths of psychological health from early adolescence to later
      adulthood.
AB  - Developmental paths of psychological health were examined for 236 participants of
      the Berkeley Growth Study, the Berkeley Guidance Study, and the Oakland Growth
      Study. A clinician-reported aggregate index, the Psychological Health Index
      (PHI), based on California Q-Sort ratings, was created for subsets of
      participants at 14, 18, 30, 40, 50, and 62 years of age. Latent curve analysis
      was then used to explicate the life span development of psychological health.
      Psychological health development could be successfully modeled via 2 piecewise
      latent growth curves. Psychological health appears to be stable in adolescence
      and to steadily increase from 30 to 62 years of age. A moderately strong positive
      correlation between the 2 developmental curves indicates that those with greater
      psychological health in adolescence show more improvement in adult psychological
      health tend to also. Results illustrate the value of the PHI and the power of
      latent curve analysis to explicate longitudinal stability and change.

PMID- 10879589
TI  - Social behavior and off-target verbosity in elderly people.
AB  - This study investigated social behavior in older adults with varying levels of
      off-target verbosity (OTV). After screening 455 adults in Phase 1, 198
      individuals were selected to participate in both a get-acquainted conversation
      and an experimental cues situation and to complete social and cognitive measures.
      Higher OTV participants had lower cognitive inhibitory scores, talked more, were
      less interested in their partners, and focused more on themselves. Their
      conversational partners were less satisfied. Age and cognitive functioning were
      not related to OTV scores or conversational style for low- and mid-range
      participants. Although high-OTV individuals talked less when exposed to social
      cues signalling boredom, they spoke more relative to other participants. Self
      reported social behavior had little relation with OTV and conversational style,
      but higher OTV individuals were less accurate in judging videotaped social
      interactions. Gender differences in conversational behavior are also discussed.

PMID- 10879590
TI  - Osteomyelitis of the ribs in the antibiotic era.
AB  - A total of 106 cases of rib osteomyelitis were reviewed, including 2 cases
      described in detail. Mycobacterial and bacterial infections accounted for 47
      cases each. Fungal rib osteomyelitis occurred in 11 cases and 1 case was caused
      by Entamoeba histolytica. Most cases occurred in children and young adults. The
      mean duration of symptoms before diagnosis was 16, 26 and 32 weeks for bacterial,
      mycobacterial and fungal rib osteomyelitis, respectively. Common clinical signs
      were fever (73%), soft tissue mass (64%) and chest pain (60%). Route of infection
      was defined in 85 cases: 62% from contiguous spread and 38% via haematogenous
      route of infection. Eighty-nine percent had a favourable outcome after
      antimicrobial therapy with or without surgery. In conclusion, rib osteomyelitis
      is a rare infection of various aetiologies. The majority of cases occur in
      children and young adults and its diagnosis is usually delayed for several weeks.

PMID- 10879591
TI  - C-reactive protein and serum amyloid A protein in neonatal infections.
AB  - In this study, we examine C-reactive protein (CRP) and serum amyloid protein A
      (SAA). Although the former is the best known and most commonly used indicator of
      inflammation, certain considerations underline the inadequacy of CRP
      determination alone for the early diagnosis of infection. In fact symptoms often
      precede the CRP elevation. SAA protein comprises a family of polymorphic
      apolipoproteins produced mainly by the liver, and several studies have stressed
      its importance in the diagnosis and monitoring of various diseases. Pathological
      SAA values are often detected in association with normal CRP concentrations. SAA
      rises earlier and more sharply than CRP. Finally, contrary to CRP, SAA presents
      the same trend in viral as well as bacterial infections. Although the data
      available on SAA in neonates are currently very limited, it is possible to
      postulate a role of primary importance for SAA in the management of neonatal
      infections.

PMID- 10879592
TI  - Herpesvirus DNA detection in cerebral spinal fluid: differences in clinical
      presentation between alpha-, beta-, and gamma-herpesviruses.
AB  - To evaluate the role of 6 human herpesviruses (cytomegalovirus (CMV), Epstein
      Barr virus (EBV), human herpesvirus-6 (HHV-6), herpes simplex virus (HSV) types 1
      and 2 and varicella zoster virus (VZV)) in infections of the nervous system,
      cerebrospinal fluid (CSF) samples from 662 patients with suspected viral
      aetiology to neurological symptoms were investigated for presence of herpesviral
      DNA in a PCR-based study. Of the 69 patients (2 patients had 2 herpesvirus DNA
      detected in CSF) who had herpesvirus DNA detected in the CSF, 60 (87%) were non
      immunocompromised (CMV 7; HHV-6 6; EBV 16; HSV-1 18; HSV-2 9 and VZV 6) and 9
      (13%) were immunocompromised (CMV 3; HHV-6 0; EBV 5; HSV-1 0; HSV-2 1 and VZV 0).
      The study was performed in a retrospective/prospective manner. The HSV-1, HSV-2,
      VZV and CMV DNA-positive patients usually had typical clinical syndromes, such as
      encephalitis/myelitis and meningitis, but also other neurological conditions were
      associated with findings of these viruses. HHV-6 and EBV DNA were detected in
      patients presenting with a variety of neurological symptoms, and in some of the
      cases, concurrent with diagnosis of other infections of the central nervous
      system. Despite the overall variability of clinical conditions seen, a pattern
      associated with each investigated herpesvirus was discernable as regards clinical
      presentation.

PMID- 10879593
TI  - Levels of viraemia in subjects with serological markers of past or chronic
      hepatitis B virus infection.
AB  - Subjects with serological markers for a past HBV infection may still have HBV DNA
      in their serum, but the levels of viraemia in such cases are not known. In the
      present study, of 63 consecutive HBsAg-negative, anti-HBc-positive serum samples
      with or without anti-HBs, 20 were HBV DNA-positive as analysed by a highly
      sensitive quantitative PCR, the Cobas Amplicor HBV Monitor test. However, all of
      these 20 samples had viraemia levels below 1000 copies/ml, compared with median
      viraemia levels of 10(8.6) and 10(4.3) copies/ml, respectively, in 98 HBeAg
      positive and 124 HBeAg-negative HBsAg carriers. There was no difference in
      viraemia between subjects with anti-HBc alone compared with both anti-HBs and
      anti-HBc, nor between those with or without hepatitis C virus antibodies. The
      findings indicate that HBsAg-negative subjects may retain a low infectivity.
      Their risk for progressive liver damage is probably low, but this deserves
      further study.

PMID- 10879594
TI  - Continued transmission of hepatitis B and C viruses, but no transmission of human
      immunodeficiency virus among intravenous drug users participating in a
      syringe/needle exchange program.
AB  - The virological efficacy of a syringe/needle exchange program was evaluated in a
      cohort incidence study. Of 698 intravenous drug users (IVDUs) initially
      recruited, 15 (2.1%) were HIV-positive at baseline. Adequate follow-up was
      possible in 515 (74%) and showed no new cases of HIV infection during a median of
      31 months. Most IVDUs had been previously exposed to HBV (anti-HBc-positive
      70.1%) and HCV (anti-HCV-positive 90.7%). Of those 159 IVDUs negative at baseline
      for anti-HBc and/or anti-HCV, 56 (35%) seroconverted to one or both viruses
      during follow-up, corresponding to 11.7 seroconversions/100 y at risk for HBV and
      26.3 seroconversions/100 y for HCV. Multiple logistic regression analysis showed
      hepatitis seroconversion to correlate with imprisonment during the study (OR 2.2;
      95% CI 1.04-4.74), absence of drug-free periods (OR 5.7; CI 1.44-22.3) and
      frequent syringe/needle exchanges (OR 1.31; CI 1.02-1.7). The absence of HIV
      spread was probably partly due to the low prevalence of HIV-infected IVDUs in the
      city. Despite free syringes and needles, both HBV and HCV continued to spread at
      high rates. Nevertheless, syringe/needle exchange programs, coupled with
      monitoring of serostatus provide good surveillance and are valuable for further
      assessment of remaining risks.

PMID- 10879595
TI  - Lack of association between TTV viral load and aminotransferase levels in
      patients with hepatitis C or non-B-C.
AB  - TT virus (TTV) is a newly identified un-enveloped single-stranded DNA virus.
      Although TTV was initially thought to be a new hepatitis virus, it is still
      unclear whether it causes hepatitis. To clarify the natural history and
      pathogenesis of TTV infection, serial serum samples from patients with chronic
      hepatitis were analysed. TTV DNA was quantified by real-time detection polymerase
      chain reaction assay (RTD-PCR), which was adapted for TTV. Five patients with
      chronic hepatitis, 4 with hepatitis C and 1 with non-B-C, were studied. The study
      period ranged from 9 to 50 months. In 3 patients there were frequent increases in
      TTV DNA titres, but no concomitant elevation of the aminotransferase (ALT)
      levels. In 2 patients who were treated with interferon, the changes in TTV titres
      were not synchronized with those of the ALT levels. Thus, in cases of chronic
      hepatitis, no correlation was observed between the serum TTV DNA titres and the
      ALT levels.

PMID- 10879596
TI  - Neurological complications of varicella-zoster virus infection in adults with
      human immunodeficiency virus infection.
AB  - This multicentre retrospective study describes the clinical features and
      prognostic significance of Varicella-zoster virus (VZV)-associated neurological
      complications. The study was performed in patients with human immunodeficiency
      virus (HIV) infection, hospitalized for VZV neurological complications, confirmed
      in every case by positive VZV polymerase chain reaction (PCR) in cerebrospinal
      fluid (CSF). Between 1990 and 1995, 34 HIV-infected patients were included in the
      study. At diagnosis, 59% had AIDS, with a median CD4 count of 11 x 10(9)/l. A
      past history of zoster was noted in 35% of cases. A concomitant herpes zoster
      rash and/or acute retinal necrosis were noted in 71% and 12% of patients,
      respectively. The predominant neurological manifestations were encephalitis (13),
      myelitis (8), radiculitis (7) and meningitis (6). The mean CSF white blood cell
      count was 126/mm3 and the mean CSF protein concentration was 2.3 g/l. Interferon
      alpha level was increased in 36% of patients. VZV was isolated from CSF cultures
      in 2/6 cases. Magnetic resonance imaging was abnormal, demonstrating encephalitis
      lesions. After intravenous antiviral therapy, complete recovery was obtained in
      18 cases (53%), serious sequelae were observed in 10 cases (29%) and 6 patients
      died (18%). Severe symptoms and a low CD4 cell count appeared to be associated
      with death or sequelae. In conclusion, VZV should be considered as a possible
      cause of encephalitis, myelitis, radiculitis or meningitis in HIV-infected
      patients, especially in patients with a history of or concomitant herpes zoster
      or acute retinal necrosis. VZV-PCR in the CSF may allow rapid diagnosis and early
      specific antiviral treatment.

PMID- 10879597
TI  - Imported and autochthonous histoplasmosis in Bergamo province, Northern Italy.
AB  - This paper reviews the Italian literature and illustrates the results of a survey
      on Histoplasma capsulatum var. capsulatum infection carried out in the Bergamo
      area of Italy over the last 10 y. During the period January 1989-July 1999, 7
      patients were diagnosed as being affected by the H. capsulatum var. capsulatum
      infection. Until 1999 41 cases have been described in the Italian literature (9
      before the 1980s, 6 in the 1980s and 26 in the 1990s). The epidemiological
      profile of histoplasmosis is well-defined: risk factors are activities such as
      visiting caves or building sites, travelling and immigration, and it affects both
      immunocompetent and patients with AIDS. However, in the past, the Italian soil
      was considered as a low-endemic pabulum for H. capsulatum var. capsulatum and
      only a few autochthonous cases of histoplasmosis have been reported in Italy,
      specifically in the Po valley. In the present series, the identification of new
      cases in the Po valley in Lombardy suggests the possible autochthonous presence
      of histoplasmosis in Italy.

PMID- 10879598
TI  - Enterococcal infections in a Greek intensive care unit: a 5-y study.
AB  - In this study we determined the incidence, resistance pattern, and mortality rate
      associated with infection caused by Enterococcus faecalis and Enterococcus
      faecium among patients in a multidisciplinary intensive care unit (ICU). A total
      of 111 patients with E. faecalis and 60 with E. faecium infections were
      identified during a 5-y period (1992-96). We observed an increase in the
      incidence of enterococcal infections (from 5.46 to 8.46 per 1000 patients-days, p
      = 0.0112), due mainly to the increased incidence of E. faecium (from 0.45 to 4.06
      per 1000 patients-days, p = 0.002). Blood was the most common site of
      enterococcus isolation. E. faecium was more resistant to antibiotics than E.
      faecalis, but no vancomycin resistant enterococcus was isolated. Patients with E.
      faecium infection had a significantly higher mortality than patients with E.
      faecalis infection (66% vs. 41.5%, p = 0.0035 for infection from any site and
      85.7 vs. 47.7%, p = 0.012 for bacteremic patients). r 4n- D I .- .- - .. . .

PMID- 10879599
TI  - Recurrence of pneumonia in relation to the antibody response after pneumococcal
      vaccination in middle-aged and elderly adults.
AB  - We have recently studied the efficacy of pneumococcal vaccine in preventing
      pneumonia recurrences after hospital treatment for community-acquired pneumonia
      in non-immunocompromised patients aged 50-85 y. Among these patients, we have now
      compared the antibody response to the pneumococcal vaccine between patients who
      developed pneumonia (n = 50) and patients without pneumonia recurrences (n =
      100), during a mean follow-up period of 32 months after vaccination. The antibody
      levels of 5 pneumococcal serotypes were measured before, and 4 weeks, 1 y and 3 y
      after vaccination. A lower risk of pneumonia recurrences was seen in patients
      with antibody fold increases (FIs) > 4 from pre-vaccination to post-vaccination
      compared with patients with lower FIs (p = 0.02). The results suggest that in
      this patient category, the antibody response to pneumococcal vaccination is of
      importance for the risk of pneumonia recurrence.

PMID- 10879600
TI  - Field detection of Francisella tularensis.
AB  - A field investigation was undertaken following an outbreak of water-borne
      tularemia in Northern Norway. Francisella tularensis bacterial cellular
      components were analysed by rapid immunochromatography (RI)-testing, enzyme
      linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). Water
      from 1 reservoir, fed from a rapid stream, tested negative. From another
      reservoir, 2 of a chain of 3 wells tested negative. The third well, at the end of
      the chain, contained lemming (Lemmus lemmus) carcasses and gave ample proof of F.
      tularensis contamination. We concluded that the origin of the outbreak was dead,
      infective lemming carcasses in the water sources. For the various sampling
      materials, the RI-test proved itself particularly handy and versatile, compared
      with the ELISA and the PCR.

PMID- 10879601
TI  - Outbreak investigation of nosocomial enterobacter cloacae bacteraemia in a
      neonatal intensive care unit.
AB  - Over a period of 7 months, 23 patients hospitalized in a neonatal intensive care
      unit (NICU) developed nosocomial Enterobacter cloacae bacteraemia. Contaminated
      saline for preparing heparin solution was initially identified as the common
      source of E. cloacae bacteraemia. Although environmental sanitation was enforced,
      the outbreak continued. E. cloacae has always been isolated from various cultures
      of the environmental specimens, from the hands of personnel and from the faeces
      of patients. All of the 23 bacteraemic isolates and 8 stool isolates from
      infected infants, as well as the 17 isolates from environmental specimens were
      found to be of the same genotype using the polymerase chain reaction-based DNA
      fingerprinting method. After various infection control methods were instituted,
      the outbreak eventually came under control. For epidemiological investigation, 23
      neonates without E. cloacae bacteraemia were matched for case-control study.
      Nineteen (83%) of the case-patients were premature. The significant risk factors
      leading to E. cloacae bacteraemia in the NICU included small gestation age, low
      birthweight, exposure to personnel with contaminated hands and the presence of E.
      cloacae in the stool carriage (p=0.003, 0.007, 0.018 and 0.040, respectively).
      The gastrointestinal tracts of the patients and environmental surfaces appeared
      to be the principal sites of bacterial reservoir. In conclusion, the outbreak of
      E. cloacae bacteraemia was caused by a particular strain and possibly via
      multiple modes of transmission, including a bottle of contaminated saline as an
      initial common source, endogenous spread from the gastrointestinal tract and
      successive cross-infections between patients, hands of personnel and the
      environment. Effective infection control requires a multidisciplinary approach
      and reinforcement of infection control procedures, including aseptic technique,
      hand washing, proper isolation and disinfection of environmental surfaces.

PMID- 10879602
TI  - Tympanic or rectal temperature measurement? A cost-minimization analysis.
AB  - In a cost-minimization study, we compared tympanic and rectal body temperature
      measurement in inpatients in a department of internal medicine. At all
      measurement volumes in a sensitivity analysis, tympanic temperature measurement
      had markedly lower average cost than rectal measurement, indicating a large
      savings potential if the former technique is used.

PMID- 10879603
TI  - Endocarditis: clinical outcome and benefit of trans-oesophageal echocardiography.
AB  - The improved prognosis for infective endocarditis (IE) seen in the last decade is
      due partly to more active surgical treatment and partly to improved diagnosis by
      echocardiography. To evaluate the clinical value of repeated trans-oesophageal
      echocardiography (TEE) 34 patients with 35 episodes of suspected IE were included
      in a prospective part of the study (group A). TEE was carried out for diagnosis,
      at discharge and about 5 months after hospitalization. Endocarditis was
      classified using Duke's criteria. In a retrospective part of the study 32 other
      patients with 34 episodes of IE were included (group B). Both groups were
      analysed regarding mortality, frequency of surgery and classification according
      to Duke. The diagnosis was regarded as definite in 49 and possible in 20
      episodes. Vegetation-size decreased significantly (p < 0.001) during treatment.
      In contrast, no significant changes in valvular insufficiency were found. In
      episodes diagnosed as definite, the mortality was 2/49 (4.1%). The low mortality
      might be explained by the high frequency of surgery (22%), the inclusion of
      patients with right-sided IE, and 'early diagnosis'. The first TEE was important
      for correct diagnosis in patients with small vegetations and for those needing
      surgery. The clinical value of the additional investigations was low in native
      valve endocarditis.

PMID- 10879604
TI  - A teratological study of aminoglycoside antibiotic treatment during pregnancy.
AB  - The aim of this study was to investigate the teratogenicity of aminoglycoside
      antibiotics, such as parenteral gentamicin, streptomycin, tobramycin and oral
      neomycin, during pregnancy. Pair analysis of cases with congenital abnormalities
      and matched healthy controls was carried out. The setting was the population
      based dataset of the Hungarian Case-Control Surveillance of Congenital
      Abnormalities, 1980-96. In total, 38,151 pregnant women who had newborn infants
      without any defects (control group) and 22,865 pregnant women who had foetuses or
      newborns with congenital abnormalities were included in the study. 38 (0.16%) and
      42 (0.11%) pregnant women in the case and control groups, respectively, were
      treated with the aminoglycosides studied. A teratogenic potential of gentamicin
      and neomycin was not indicated by a comparison of the occurrence of
      aminoglycoside antibiotic treatments in the total control group as referent with
      the figures of different congenital abnormality groups. In addition, the case
      control pair analysis during the second-third months of pregnancy did not show a
      teratogenic risk of gentamicin and neomycin. The conclusion of this study is that
      treatment with parenteral gentamicin and oral neomycin during pregnancy presents
      no detectable teratogenic risk to the foetus, when restricted to structural
      developmental disturbances.

PMID- 10879605
TI  - Response to hepatitis B vaccine in HBsAg/anti-HBs negative and anti-HBc positive
      subjects.
AB  - Some anti-HBc positive subjects have been encountered in the absence of hepatitis
      B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs). The aim of
      this study was to evaluate the response to hepatitis B vaccination in such cases.
      A total of 33 subjects who were HBsAg and anti-HBs negative, anti-HBc positive,
      with normal serum aminotransferase levels were included in the study. A
      recombinant hepatitis B vaccine was administered to subjects. Sera samples were
      obtained 1 month after each vaccination and tested for anti-HBs. HBV DNA and
      HBeAg were not detected in any subject. Anti-HBs levels were measured above 10 >
      or = mIU/ml in 48.4% of cases after the first vaccination, 63.6% after the second
      vaccination and 90.9% after the third vaccination. Only 3 subjects (9.1%) lacked
      antibody response in spite of the 3-dose vaccination. In conclusion, preventive
      antibody levels were obtained after HBV vaccination in most of the HBsAg, anti
      HBs negative, anti-HBc positive persons.

PMID- 10879606
TI  - Cat scratch disease in 2 siblings presenting as acute gastroenteritis.
AB  - The cases of 2 siblings with cat scratch disease are described who presented with
      symptoms suggestive of acute febrile gastroenteritis. The first patient, a 7.5-y
      old girl, developed mesenteric lymphadenitis, hepatosplenic granulomas and
      osteolytic bone lesions only late in the course of her protracted illness. Her 3
      y-old brother had a shorter, self-limited illness without complications. Cat
      scratch disease is often unrecognized and the full spectrum of its clinical
      manifestations remains to be investigated.

PMID- 10879607
TI  - CNS infection with clostridium septicum.
AB  - We present an unusual case of Clostridium septicum brain infection in a 72-yr-old
      woman who had no underlying malignant disease. The infection spread from a
      localized sit to the CNS causing gas formation. The patient died rapidly.

PMID- 10879608
TI  - Streptococcus salivarius acute meningitis with latent petromastoiditis.
AB  - A 48-y-old woman, with a previous history of neurosurgical intervention for a
      trigeminal neurinoma, presented with acute meningitis due to Streptococcus
      salivarius. There were significant changes in the petrous region, as revealed by
      MRI, leading to the diagnosis of associated latent subacute mastoiditis.

PMID- 10879609
TI  - Eikenella corrodens prosthetic valve endocarditis in a patient with ulcerative
      colitis.
AB  - A 33-y-old male with ulcerative colitis developed prosthetic valve endocarditis
      (PVE) caused by Eikenella corrodens. The outcome of conservative treatment was
      successful. Only 2 cases of E. corrodens PVE were found in a survey of the
      English-language medical literature. In contrast to previous data indicating that
      eikenella infections usually derive from the oral cavity, our patient most likely
      acquired the infection by colonoscopy and mucosal biopsies, which were performed
      a few days before onset of the disease.

PMID- 10879610
TI  - Gallium-67 scanning in endogenous Klebsiella endophthalmitis with unknown primary
      focus.
AB  - A whole-body gallium-67 (Ga-67) scan of a 61-y-old male with diabetes mellitus
      who suffered from endogenous Klebsiella endophthalmitis is reported. The scan
      revealed right orbital and lower abdominal lesions. Urinary analysis revealed
      pyuria. The causes of endogenous Klebsiella endophthalmitis and the usefulness of
      Ga-67 are discussed.

PMID- 10879611
TI  - Successful treatment of mycobacterium avium osteomyelitis and arthritis in a non
      immunocompromised child.
AB  - In non-immunocompromised children, infections with mycobacterium avium complex
      (MAC) are rare, except for cervical lymphadenitis. We report here a 34-month-old
      boy who developed osteomyelitis and septic arthritis due to MAC. No findings
      could be revealed for immunodeficiency. He was treated successfully for 12 months
      with combined therapy consisting of clarithromycin, rifabutin and protionamid.

PMID- 10879612
TI  - Primary actinomycosis of the urinary bladder.
AB  - Actinomycosis is caused by bacilli of the Actinomyces sp. They are Gram-positive,
      anaerobic or microaerophilic non-spore-forming bacilli. Actinomyces israelii is
      the most common aetiological agent. A case is reported of primary actinomycosis
      in the urinary bladder successfully treated with ceftriaxone.

PMID- 10879613
TI  - Cutaneous infection caused by Paecilomyces lilacinus in a renal transplant
      patient: treatment with voriconazole.
AB  - Moulds belonging to the genus Paecilomyces are rare opportunistic pathogens.
      About 100 cases have been reported in immunocompromised hosts or in relation to
      surgical procedures. We describe here a cutaneous infection due to P. lilacinus
      in a renal transplant patient, which responded to voriconazole treatment.

PMID- 10879614
TI  - Drug-induced acute malaria.
AB  - The case of an elderly woman with asymptomatic P. malariae infection that acutely
      reactivated after 45 y of latency following treatment with chlorambucil and
      methylprednisolone is reported. Only 1 similar case with methotrexate-induced
      acute malaria has been reported in the English literature thus far.

PMID- 10879615
TI  - Familial Mediterranean fever diagnosed by PCR.
AB  - The diagnosis of familial Mediterranean fever (FMF) was, until recently, based on
      exclusion of diseases with related clinical signs. Now an exact diagnosis of FMF
      is possible by polymerase chain reaction (PCR). We report here a case with 2
      different mutations in the gene responsible for FMF, thereby being a compound
      heterozygote (M694V/V726A).

PMID- 10879616
TI  - Liver and brain mucormycosis in a diabetic patient type II successfully treated
      with liposomial amphotericin B.
AB  - A case of liver and brain mucormycosis in a 73-y-old diabetic patient is
      described. The patient presented with fever and a moderate, tender hepatomegaly
      and a C/T scan examination of the abdomen and brain showed multiple hepatic and
      cerebral nodular lesions. The largest of the liver lesions was aspirated and
      broad hyphae of mucor were demonstrated in the purulent material obtained. The
      patient was treated successfully (for 40 d) with intravenous liposomal
      amphotericin B and then with itraconazole for 3 months. To our knowledge, this is
      the first case of a diabetic patient with both liver and brain mucormycosis who
      has been treated successfully.

PMID- 10879617
TI  - Serotypes and antimicrobial susceptibility of group B streptococcus isolated from
      neonates in Casablanca.
AB  - The serotypes and the levels of antibiotic resistance of 59 Streptococcus
      agalactiae isolates from neonates in Casablanca, from February 1992 to July 1997,
      were studied. Most of the isolates (86.4%) were recovered from early-onset
      disease. The serotype distribution was as follows: serotype III 39%; serotype Ia
      32.2%; and serotype V 10.2%. All strains were susceptible to penicillin G,
      cefotaxime and ampicillin, whereas 1 strain was resistant to erythromycin. No
      high level of resistance to gentamicin was detected. A vaccine should comprise
      the most prevalent serotypes and also provide protection against serotype V
      disease. The antibiotic susceptibility patterns reported here support the
      recommended treatment and prophylaxis of invasive group B Streptococcal disease.

PMID- 10879618
TI  - Local delivery of a low molecular weight heparin following stent implantation in
      the pig coronary artery.
AB  - BACKGROUND: The low molecular weight heparin Reviparin reduces smooth muscle cell
      proliferation in cell culture experiments. Clinical studies with systemic
      application of the substance did not show a reduction of the incidence of
      restenosis following balloon angioplasty. Local delivery, by achieving higher
      local concentrations of the drug, may have the potential to decrease smooth
      muscle cell proliferation in the treated arterial segment. OBJECTIVES: The aim of
      this study was to investigate the effects of local delivery of reviparin
      following stent implantation in the pig coronary artery. METHODS: A coronary
      stent was implanted in the LAD of 34 pigs. In the treatment group 5 ml reviparin
      was injected with the Infusasleeve catheter at a proximal pressure of 80 psi.
      After 28 days the animals were sacrificed. Quantitative morphometric analysis
      comprised the intimal area, medial area and the lumen. The extent of vessel
      injury and the intimal thickness were assessed separately for each stent strut
      region. The correlation of injury and neointimal thickness was analysed using
      linear regression. RESULTS: There was no relevant difference in the extent of
      vessel injury (1.9 +/- 0.7 vs. 1.6 +/- 0.6), the neointimal areas (2.4 +/- 0.9
      vs. 2.4 +/- 1.0 mm2) and the resulting stenosis (46 +/- 18 vs. 47 +/- 17%). The
      medial area was larger in the animals treated with local delivery (2.2 +/- 0.4
      vs. 1.6 +/- 0.4 mm2; p < 0.01). The correlation of injury and neointimal
      thickness was comparable in both groups. In two animals the passage of the stent
      area with the delivery system resulted in stent dislocation and fatal subacute
      thrombosis. CONCLUSION: In this animal model, local delivery of reviparin with
      the Infusasleeve catheter did not result in a reduction of neointimal
      proliferation following stent implantation. Local delivery after stent
      implantation carries the risk of stent dislocation as a result of the passage
      with the delivery system.

PMID- 10879619
TI  - A new rat model of small vessel stenting.
AB  - OBJECTIVES: Restenosis is the major complication of coronary angioplasty and
      stenting. In addition, the small vessel diameter represents a major limitation to
      the wide use of the technology. The aim of this study was to assess the
      feasibility and the vascular response of stent deployment in rat small vessels.
      METHODS: In 40 Wistar rats (500-550 g) a Nir stent crimped on a 1.5 mm Comet
      angioplasty balloon catheter was deployed at high pressure in the common carotid
      artery. Neointimal area, neointima/media ratio and the arterial dimension were
      assessed immediately and at 7, 14, 21, and 28 days after stenting. RESULTS: After
      stent deployment, the neointimal area and the neointima/media ratio increased
      progressively and peaked at 14 days (p < 0.05 vs 0 and 7 days). Alpha-actin
      positive cells were found circumferentially organized on the lumen surface. At 21
      and 28 days after stenting, the neointima and the neointima/media ratio were not
      statistically different compared with the results obtained fourteen days after
      stent deployment. No significant differences in the area of external elastic
      lamina were observed during the study period. In contrast, the internal lumen
      area was reduced significantly at 14, 21, and 28 days after the stent deployment.
      Subacute thrombosis rate after stent implantation was 26.5 %. CONCLUSIONS: The
      results of this study demonstrated that the balloon expandable stents can be
      safely placed into rat arteries and the reduction of the internal arterial lumen
      observed after stent deployment was only due to the neointima formation whereas
      remodeling did not occur.

PMID- 10879620
TI  - Arrhythmogenic potential of positive inotropic agents.
AB  - The clinical use of positive inotropic agents has been associated with increased
      mortality, with proarrhythmia speculated to be a contributing factor. This study
      compares the arrhythmogenic potentials of six positive inotropic agents
      representing different mechanistic classes: the beta-adrenergic agonist
      dobutamine, the adenylyl cyclase activator forskolin, the phosphodiesterase-III
      inhibitor milrinone, the cardiac glycoside ouabain, and the sodium channel
      agonists DPI 201-106 and BDF 9148. These agents were studied in dogs with
      anterior myocardial infarction using lower and higher dose i.v. regimens targeted
      to elicit 20-40% and 70-90% increases in LV+dP/dt, respectively. Precipitation of
      new ventricular arrhythmia by programmed ventricular stimulation was observed in
      all treatment groups. Incidences of new arrhythmia were comparable in the lower
      dose regimens, ranging from 16.7% (3/18 animals with BDF 9148) to 31.6% (6/19
      animals with DPI 201-106), and in the higher dose regimens, ranging from 10.0%
      (1/10 animals with milrinone) to 27.7% (5/18 animals with DPI 201-106). The
      overall incidence of new ventricular arrhythmia ranged from 27.3% (3/11 animals
      with ouabain) to 47.4% (9/19 animals with DPI 201-106). No differences were
      observed in underlying infarct size or time from infarction to electrophysiologic
      study between subgroups of animals in which new arrhythmias were precipitated vs.
      those remaining non-responsive in any treatment group. The positive inotropic
      agents tested displayed diverse total group effects on heart rate,
      electrocardiographic intervals including QTc and ventricular refractoriness.
      Within individual treatment comparisons revealed a general but not universal
      pattern of greater ventricular refractory period values in newly inducible vs.
      non-inducible subgroups in the DPI 201-106, BDF 9148 and ouabain (low and high
      dose); milrinone and dobutamine (high dose) treatment groups. These findings
      indicate that regardless of underlying cellular mechanism of action, the six
      positive inotropic agents tested all displayed comparable proarrhythmic
      potentials unrelated to underlying infarct size and time from infarction. This
      observation suggests the general shared property of increased myocardial
      contractility, potentially adversely affecting myocardial oxygen balance,
      myocardial perfusion and electrical stability in the setting of previous
      myocardial infarction, to be a common underlying cause for arrhythmogenesis.
      Additionally, alterations in ventricular refractoriness and repolarization may
      contribute significantly to proarrhythmia with some positive inotropic
      interventions.

PMID- 10879621
TI  - Effects of selenium deficiency on the rat myocardial protein pattern--
      investigation by two-dimensional gel electrophoresis.
AB  - Dietary selenium deficiency represents an etiological factor in "Keshan disease",
      a distinct form of an endemic cardiomyopathy. The biochemical effects of selenium
      depletion in the myocardium are, however, not yet known. Therefore, we
      investigated the changes in the myocardial protein pattern in rats after long
      term selenium deficiency. The myocardial proteins were analyzed in samples from
      five selenium-depleted rats (Se-deficient group) and five rats supplied with
      adequate amounts of the element (Se-adequate group). Isoelectric focusing (IEF)
      with carrier ampholytes on large 2-DE gels was used for the separation of
      proteins in the first dimension and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) for the second dimension. The protein patterns were
      evaluated by means of a computer-assisted gel analysis system. The biochemical
      identification of the proteins of interest was achieved by matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI) or immunoblotting. On average,
      588 +/- 68 protein spots were found on the gels. No significant difference in
      spot numbers existed between the groups. A pattern of 270 spots with identical
      positions was found on every gel; 247 of these spots were not saturated and used
      for quantitative comparison. Thirty-five, i.e., 14 %, differed significantly in
      their relative intensity in the two groups. Twenty-eight protein spots were
      decreased in the Se-deficient group and seven were increased. Sarcomeric creatine
      kinase M chain, alpha-myosin heavy chain (alpha-MHC) and myosin light chain 1 and
      2 (MLC 1 and 2) were largely decreased in Se-deficiency. Three protein spots were
      increased by more than twofold or appeared only in the Se-deficient group. A
      mitochondrial creatine kinase was identified in this group. The results suggest
      that selenium deficiency affects myocardial energy metabolism and contractile
      proteins. These changes probably reflect non-specific alterations in heart
      failure.

PMID- 10879622
TI  - Early rather than delayed administration of lisinopril protects the heart after
      myocardial infarction in rats.
AB  - BACKGROUND: ACE inhibitors have shown beneficial results in several studies after
      myocardial infarction (MI). However, these studies have shown conflicting results
      about the ideal starting time of the ACE inhibitors administration after MI and
      the importance of infarct size. OBJECTIVES: This study was designed to assess the
      long-term effects of lisinopril on mortality, cardiac function, and ventricular
      fibrosis after MI, in rats. METHODS: Lisinopril (20 mg/kg/day) was given on day 1
      or 21 days after coronary occlusion in small or large infarctions. RESULTS: The
      mortality rate was reduced by 39 % in early treatment and 30 % in delayed
      treatment in comparison to the untreated rats. Early treatment reduced cardiac
      dysfunction in small MIs; however, delayed treatment did not. No statistical
      difference was observed among the groups for large MIs. No statistical difference
      was observed among the groups with large or small MIs on myocardial
      hydroxyproline concentration. CONCLUSIONS: Both early and delayed treatments with
      lisinopril increased survival. Treatment exerts no marked effects on fibrosis;
      early treatment has exerted beneficial influences on cardiac function whereas
      delayed treatment had no consistent effects. The protective effect of lisinopril
      is detectable only in small (< 40 % of LV) MIs.

PMID- 10879623
TI  - A role of PKC in the improvement of energy metabolism in preconditioned heart.
AB  - OBJECTIVE: A possible link between activation of PKC and improvement of energy
      metabolism during reperfusion in ischemic preconditioning hearts was examined.
      METHODS: Isolated perfused rat hearts were preconditioned by 5-min ischemia and 5
      min reperfusion in the presence and absence of a PKC inhibitor polymyxin B (50
      microM) and then subjected to 40-min sustained ischemia and subsequent 30-min
      reperfusion. In another set of experiments, the hearts pretreated with and
      without a PKC activator PMA (15 pmol/5 min) were subjected to the sustained
      ischemia and reperfusion. Myocardial high-energy phosphates, glycolytic
      intermediates and mitochondrial oxygen consumption capacity were determined at
      appropriate experimental sequences. RESULTS: Preconditioning enhanced the
      recovery of cardiac function such as left ventricular developed pressure, heart
      rate and rate-pressure product of the reperfused heart, suppressed the release of
      creatine kinase, enhanced the reperfusion-induced restoration of myocardial high
      energy phosphates, attenuated the reperfusion-induced accumulation in glucose 6
      phosphate and fructose 6-phosphate contents, abolished the ischemia-induced
      increase in tissue lactate content and prevented the ischemia-induced decrease in
      mitochondrial oxygen consumption capacity. Treatment of the perfused heart with
      PMA mimicked the effects of preconditioning on post-ischemic contractile
      function, enzyme release, levels of myocardial energy store, glycolytic
      intermediates and lactate, and mitochondrial function. Polymyxin B-treatment
      abolished the preconditioning-induced recovery of post-ischemic contractile
      function, the suppression of the release of CK, the restoration of myocardial
      energy store, and the preservation of mitochondrial function, whereas it did not
      cancel the improvement of glycolytic intermediate levels and the reduction in
      tissue lactate accumulation. Post-ischemic contractile function was closely
      related to restoration of high-energy phosphates and mitochondrial oxygen
      consumption capacity in all hearts subjected to ischemia/reperfusion. CONCLUSION:
      The results suggest that activation of PKC and preservation of mitochondrial
      function are closely linked with each other in the preconditioned heart, which
      may lead to the improvement of post-ischemic contractile function.

PMID- 10879624
TI  - 5-HD abolishes ischemic preconditioning independently of monophasic action
      potential duration in the heart.
AB  - OBJECTIVE: Blocking of the KATP channel with either glibenclamide or 5
      hydroxydecanoate (5-HD) has been shown to abolish the infarct reducing effect of
      ischemic preconditioning (IPC) in hearts from several species, but the results in
      rat and rabbit have been equivocal. In this study we investigated if 5-HD could
      abolish IPC in rat and rabbit and further if IPC or IPC + 5-HD were affecting
      action potential duration in the rabbit heart. METHODS: The rat hearts were
      isolated and retrogradely perfused on a Langendorff perfusion apparatus with
      Krebs-Henseleit buffer. The rabbit experiments were performed in an in situ
      model. Rat and rabbit hearts were subjected to 30 min regional ischemia by
      ligating a coronary artery followed by 120 min (rat) or 150 min (rabbit) of
      reperfusion. The preconditioning protocol was one or three cycles of 5 min
      ischemia plus 5 min reperfusion in the rat and one cycle of 5 min ischemia plus
      10 min reperfusion in the rabbit. In the rat 5-HD was added to the reservoir
      before ischemic preconditioning in different concentrations, and in the rabbit 5
      HD was given as a bolus 5 mg/kg intraventricularly 2 min before the
      preconditioning ischemia. In the rabbit epicardial monophasic action potential
      duration at 50 % repolarization (MAPD50) was measured at 1, 2 and 5 min in each
      of the ischemic periods using a contact pressure electrode. Infarcts were
      measured with tetrazolium staining and risk zone volumes with fluorescent
      microspheres. RESULTS: All data are presented as infarct size in % of risk zone
      volume (mean +/- SEM). In the rat 200 microM of 5-HD abolished the protective
      effect of one cycle of IPC (28.6 +/- 4.7 versus 8.4 +/- 0.8) and 500M of 5-HD
      abolished three cycles of IPC (50.7 +/- 7.8 versus 8.4 +/- 2.0). Control was 40.9
      +/- 2.8. In the rabbit 5-HD abolished IPC (41.2 +/- 7.2 versus 8.1 +/- 3.2).
      Control was 53.5 +/- 12.4. MAPD50 were significantly more shortened compared to
      control at 1 and 2 min into the 30 min ischemia for the IPC and IPC+5-HD.
      CONCLUSIONS: We conclude that 5-HD abolishes ischemic preconditioning when given
      before the preconditioning ischemia in both rat and rabbit but does not abolish
      the ischemia induced shortening of the action potential duration in the rabbit;
      thus, a role for the mitochondrial KATP channel and not the sarcolemmal KATP
      channel in the protective mechanism behind IPC is probable.

PMID- 10879625
TI  - Diadenosine tetraphosphate (AP4A) mimics cardioprotective effect of ischemic
      preconditioning in the rat heart: contribution of KATP channel and PKC.
AB  - Diadenosine tetraphosphate (AP4A) administration is reported to mimic the effect
      of ischemic preconditioning (PC) via purine 2y receptors (P2yR) and adenosine
      receptors. This study was designed to test the contributions of the ATP-sensitive
      potassium channel (KATP channel) and protein kinase C (PKC), two of the main
      regulator in PC, to the effect of AP4A. Isolated buffer-perfused rat hearts were
      subjected to 20 min of global ischemia (37 degrees C) and 20 min of reperfusion.
      Three cycles of 1-min ischemia and 3-min reperfusion induced PC. Chemicals were
      administrated for 2 min before 20 min of ischemia. AP4A (10 microM)
      administration was as effective as PC in improving the recovery of post-ischemic
      contractile function and reducing creatine kinase leakage after reperfusion,
      whereas adenosine (10 and 100 microM) have not effect. AP4A had not effect on
      reperfusion-induced arrhythmia, whereas PC significantly prevented it. These
      effects of AP4A and PC were reversed by co-administration of glibenclimade (KATP
      channel blocker, 100 microM) and GF109203X (PKC inhibitor, 10 microM); the
      effects of AP4A but not PC were reversed by co-administration of reactive blue
      (P2yR antagonist, 13 nM). AP4A appears to activate the KATP channel and PKC via
      P2yR mimic the effects of PC in part. The role of P2yR indicated that trigger
      mechanism of the effect of PC and AP4A administration might differ in rat hearts.

PMID- 10879626
TI  - Delayed cardioprotection in a human cardiomyocyte-derived cell line: the role of
      adenosine, p38MAP kinase and mitochondrial KATP.
AB  - Evidence of delayed preconditioning (PC) in man is limited. Adenosine is proposed
      as a trigger via action on the A1 receptor in many species and the mitochondrial
      KATP channel is a likely end effector. We examined the ability of a brief,
      simulated ischemic episode on day one to provide delayed cardioprotection against
      lethal, simulated ischemia on day two in a human cardiac cell line with reference
      to the role of adenosine, the p38MAP kinase signalling pathway and mitochondrial
      KATP channel. RESULTS: PC and adenosine administered on day 1 protected against
      cell death on day 2 as measured by LDH release and propidium iodide (PI)
      exclusion: (%LDH release: PC: 12.1 +/- 1.1%, ADO: 11.9 +/- 2.0% vs control: 36.4
      +/- 1.1%; %PI positive: PC: 14.6 +/- 1.4%, ADO: 17.9 +/- 2.0% vs control: 34.4 +/
      2.0% respectively). This protection is abolished by treatment with SB203580
      prior to the protective stimulus on day 1: [PC + SB (%LDH release 28.6 +/- 2.8%;
      %PI positive 34.7 +/- 2.2%) and ADO + SB (%LDH release 25.3 +/- 2.9%; %PI
      positive 33.7 +/- 7.3)]. Similarly 5-hydroxydecanoate abolished protection, when
      given immediately prior to lethal simulated ischemia on day 2: [PC + 5-HD; (%LDH
      release 31.9 +/- 4.8%; %PI positive 29.5 +/- 2.0%) and ADO + 5-HD (%LDH release
      36.9 +/- 4.0%; %PI positive 34.8 +/- 2%)]. CONCLUSION: In this model delayed PC
      can be mimicked by adenosine and involves the p38MAP kinase pathway and the
      mitochondrial KATP channel.

PMID- 10879627
TI  - Do KATP channels open as a prominent and early feature during ischaemia in the
      Langendorff-perfused rat heart?
AB  - The objective was to investigate whether myocardial adenosine triphosphate
      sensitive K+ (KATP) channels open during the first 10 min of regional ischaemia
      in Langendorff-perfused rat hearts. Changes in monophasic action potentials and
      arrhythmias were studied during myocardial ischaemia in both the presence and
      absence of pharmacological KATP modulation. Ligation of the left main coronary
      artery for 10 min did not shorten the action potential duration (APD). The APD50
      and APD80 (15.5 +/- 1.0 and 38.1 +/- 2.3 ms, respectively [mean +/- S.E., n = 15
      hearts], immediately prior to ligation) increased transiently during the first 4
      min of ligation (by 160 and 79% respectively, P < 0.05), before returning to pre
      ligation values, but without a significant below-baseline-shortening. The cardiac
      electrogram showed no accompanying ventricular tachyarrhythmia (VT). These
      results raised the possibility that the myocardial KATP channels had not opened
      during the ligation. The KATP opener Ro 31-6930 (0.5 and 5 microM) shortened the
      APD50 and APD80 during coronary ligation, to significantly below both their
      control and pre-occlusion values (P < 0.05), and caused a concentration-dependent
      increase in both the incidence and duration of VT during the ligation. Ro 31-6930
      at 5 microM also shortened APD50 and APD80 even before ligation (by 50 and 62%
      respectively, P < 0.05), and abolished the normal APD-lengthening seen during
      ischaemia. The KATP blocker glibenclamide (1 microM) abolished both the APD
      shortening and pro-arrhythmic effects of the KATP opener, both before and during
      coronary ligation, yet when delivered on its own, at the same concentration which
      abolished the effects of KATP activation, it had no significant effect on the APD
      changes seen during the coronary ligation alone. These results suggest that, in
      Langendorff-perfused rat hearts in the absence of drugs, KATP channels do not
      open during early myocardial ischaemia.

PMID- 10879628
TI  - X-ray densitometry for the measurement of regional myocardial perfusion.
AB  - The evaluation of regional myocardial blood flow (RMBF) during cardiac
      catheterization is of particular diagnostic interest. The purpose of this
      investigation was to validate x-ray densitometric parameters for the evaluation
      of RMBF. In five anesthetized dogs, arterial flow in the circumflex coronary
      artery was measured continuously with an electromagnetic flowmeter, and RMBF was
      determined by colored microspheres. Five different perfusion levels were created
      by mechanical obstruction of the coronary artery or by intravenous infusion of
      adenosine. At each steady-state perfusion level, digital subtraction coronary
      angiograms were obtained for densitometric analysis. Results documented a close
      correlation between the related time parameters 1/Mean Transit Time (1/MTT, r2 =
      0.969), and 1/Rise Time (1/RT, r2 = 0.965) and RMBF over a wide range between
      0.36 ml/(min x g) and 11.16 ml/(min x g). Maximum myocardial contrast density
      (Imax) also showed a good, but inverse correlation (r2 = 0.889) with RMBF and,
      therefore, did not reflect vascular volume. Contrast medium Appearance Time (AT)
      showed no correlation to RMBF (r2 = 0.017). Repeat densitometric measurements for
      different perfusion levels revealed a good reproducibility for MTT (accuracy:
      0.001 s; precision: 0.447 s or 6.7 %) and RT (accuracy: 0.014 s; precision: 0.202
      s or 10.4 %), while AT (accuracy: 0.072 s; precision: 0.420 s or 68.5%) and Imax
      (accuracy: 0.022 GL; precision: 1.197 GL or 44.5%) showed substantial variation.
      Myocardial perfusion reserve (MPR) calculated from RT (r2 = 0.90) or MTT (r2 =
      0.94) showed better correlations to RMBF reserve than MPR calculated from AT (r2
      = 0.04). In conclusion, only 1/MTT and 1/RT showed a good reproducibility and a
      close correlation to RMBF. Therefore, only these parameters can be recommended
      for calculations of RMBF and its reserve under clinical conditions.

PMID- 10879629
TI  - Peroxisomal ghosts are intracellular structures distinct from lysosomal
      compartments in Zellweger syndrome: a confocal laser scanning microscopy study.
AB  - Peroxisome ghosts are aberrant peroxisomal structures found in cultured skin
      fibroblasts from patients affected by Zellweger Syndrome (ZS), a genetic disorder
      of peroxisomal assembly. They contain peroxisomal integral membrane proteins
      (PxIMPs) and they lack most of the matrix enzymes that should be inside the
      organelle (Santos et al., Science 239 (1988) 1536-1538). Considerable evidence
      indicates that these ghosts result from genetic defects in the cellular machinery
      for importing newly-synthesized peroxisomal proteins into the organelle. In
      contrast to these observations, (Heikoop et al., Eur. J. Cell Biol. 57 (1992) 165
      171) report that in Zellweger Syndrome, peroxisomal membranes are located within
      lysosomes and/or contain lysosomal enzymes. We have undertaken a more detailed
      and systematic investigation of this matter, employing confocal laser scanning
      microscopy (CLSM). In fibroblasts derived from ZS patients belonging to different
      complementation groups, peroxisomes were labeled with antibodies against PxIMPs
      and lysosomes were labeled with an antibody against a lysosome associated
      membrane protein (LAMP-2) or with LysoTracker. The results unambiguously
      demonstrated no appreciable colocalization of PxIMPs and LAMPs (or LysoTracker),
      indicating that peroxisomal ghosts are distinct subcellular structures, occupying
      separate subcellular locations.

PMID- 10879630
TI  - The mitogen-activated protein kinase p38 pathway is conserved in metazoans:
      cloning and activation of p38 of the SAPK2 subfamily from the sponge Suberites
      domuncula.
AB  - Our recent data suggest that during auto- and allograft recognition in sponges
      (Porifera), cytokines are differentially expressed. Since the mitogen-activated
      protein kinase (MAPK) signal transduction modulates the synthesis and release of
      cytokines, we intended to identify one key molecule of this pathway. Therefore, a
      cDNA from the marine sponge Suberites domuncula encoding the MAPK was isolated
      and analyzed. Its encoded protein is 366 amino acids long (calculated Mr 42 209),
      has a TGY dual phosphorylation motif in protein kinase subdomain VIII and
      displays highest overall similarity to the mammalian p38 stress activated protein
      kinase (SAPK2), one subfamily of MAPKs. The sponge protein was therefore termed
      p38_SD. The overall homology (identity and similarity) between p38_SD and human
      p38alpha (CSBP2) kinase is 82%. One feature of the sponge kinase is the absence
      of threonine at position 106. In human p38alpha MAPK this residue is involved in
      the interaction with the specific pyridinyl-imidazole inhibitor; T106 is replaced
      in p38_SD by methionine. Inhibition studies with the respective inhibitor SB
      203580 showed that it had no effect on the phosphorylation of the p38 substrate
      myelin basic protein. A stress responsive kinase Krs_SD similar to mammalian
      Ste20 kinases, upstream regulators of p38, had already previously been found in
      S. domuncula. The S. domuncula p38 MAPK is phosphorylated after treatment of the
      animal in hypertonic medium. In contrast, exposure of cells to hydrogen peroxide,
      heat shock and ultraviolet light does not cause any phosphorylation of p38. It is
      concluded that sponges, the oldest and most simple multicellular animals, utilize
      the conserved p38 MAPK signaling pathway, known to be involved in stress and
      immune (inflammatory) responses in higher animals.

PMID- 10879631
TI  - The response of junctional complexes to induced desquamation in mouse bladder
      urothelium.
AB  - During desquamation, the cells of mouse urinary bladder epithelium undergo
      detachment. In this process we examined the disconnection of cell adhesion
      molecules. Two proteins of cell junctions were studied: ZO1 of tight junctions
      and desmoplakin of desmosomes. Desquamation was induced by intravesical injection
      of LPS, constant illumination of mouse for 96 h, application of a combination of
      stress hormones hydrocortisone and norepinephrine or by removal of calcium with
      EGTA. All the inducers caused penetration of lanthanum tracer through the tight
      junctions, indicating paracellular permeability. Dilatation of extracellular
      spaces between neighboring cells was seen whenever desquamation was induced in
      bladders containing urine. Desquamation of single cells as well as groups of
      cells was observed. Contrary to obvious disconnection of cell junctions, as a
      precondition for desquamation, the distribution of junctional proteins did not
      change either in urothelial tissue or in desquamated cells. This study
      demonstrates that all the inducers of desquamation cause first an extensive
      dysfunction of a blood urine barrier and after that an occasional mechanical
      disconnection of adhesive junctions which consequently leads to desquamation.

PMID- 10879632
TI  - Caspase-3 protease activation during the process of genistein-induced apoptosis
      in TM4 testicular cells.
AB  - The role of caspase-3 (CPP32) protease in the molecular pathways of genistein
      induced cell death in TM4 cells was investigated. Fluorescence microscopy with
      Hoechst-33258-PI nuclear stain was used to distinguish between apoptosis and
      necrosis pathways of cell death. The viability of the test cells was assessed
      with both the trypan blue exclusion and MTT tetrazolium (3-[4,5-dimethyl-thiazol
      2-yl]-2,5-diphenyltetralzolium bromide, 2.5 mg/mL) assays. Caspase-3 enzymatic
      activity was determined using CasPASE Apoptosis Assay Kit. The overall results
      from all the data demonstrated that: i) genistein exerts dose- and time-dependent
      effects on TM4 testis cells; ii) apoptosis is induced by lower concentrations of
      genistein and necrosis induced by higher concentrations of genistein; iii)
      genistein induced activation caspase-3 enzymatic activity; iv) genistein
      induction of apoptosis and necrosis was significantly inhibited by the caspase-3
      inhibitor, z-DEV-FMK; v) sodium azide induced necrosis without activation of
      CPP32 enzymatic activity, and induction of apoptosis; and vi) genistein-induced
      apoptosis was associated with activation of CPP32 enzymatic activity in the
      cells. The overall results indicate a strong evidence of caspase-3 (CPP332)
      mediation in the molecular pathways of genistein-induced apoptosis in testicular
      cells. Apoptosis is the physiologically programmed cell death in which intrinsic
      mechanisms participate in the death of the cell, in contrast to necrosis, which
      induces inflammatory response in the affected cell. The fact that the
      chemopreventive role of several cancer drugs is due to induction of apoptosis
      augments the biotherapeutic potential of genistein for the treatment of malignant
      diseases including prostate and testicular cancers. It is therefore inevitable
      that identification of the apoptotic pathways and the points at which regulation
      occurs could be instrumental in the design of genistein biotherapy for such
      diseases.

PMID- 10879633
TI  - The nuclear matrix of Euglena gracilis (euglenophyta): a stage of nuclear matrix
      evolution?
AB  - Euglena gracilis cell was extracted sequentially with CSK-Triton buffer, RSB
      Magik solution and DNase-As solution. DGD embedment-free electron microscopy
      showed that in the extracted nucleus there was a residual non-chromatin fibrous
      network. That it could not be removed by hot trichloroacetic acid further
      supported the idea that it was a non-histone, non-chromatin fibrous protein
      network, and should be the internal network of the nuclear matrix. After the
      sequential extraction, the nuclear membrane was removed, leaving behind a layer
      of lamina; the chromatin was digested and eluted from the dense chromosomes and
      residual chromosomal structures that should be chromosomal scaffold were
      revealed. Western blot analysis with antiserum against rat lamins showed that
      nuclear lamina of the cell possessed two positive polypeptides, a major one and a
      minor one, which had molecular masses similar to lamin B and lamin A,
      respectively. Comparing these data with those of the most primitive eukaryote
      Archezoa and of higher eukaryotes, it was suggested that the lower unicellular
      eukaryote E. gracilis already had the nuclear matrix structure, and its nuclear
      matrix (especially the lamina) might represent a stage of evolutionary history of
      the nuclear matrix.

PMID- 10879634
TI  - Unusual presentations of infectious diseases.

PMID- 10879635
TI  - Metastatic complications of Staphylococcus aureus septicemia. To seek is to find.
AB  - Improvement in the high mortality from Staphylococcus aureus septicemia must
      address the individualized treatment (surgery and/or prolonged antibiotic
      treatment) of metastatic complications. The aim of this study was to evaluate the
      results of a comprehensive diagnostic monitoring for metastatic complications in
      S. aureus septicemia. 68 consecutive patients with S. aureus septicemia were
      prospectively followed. The performance rate and results of chest X-ray,
      echocardiography, bone scintigraphy and leukocyte scintigraphy are described.
      Metastatic complications were found in 53% of the 68 patients, endocarditis in
      26%. Positive findings resulted in surgical intervention in 23 patients. The
      total mortality defined as all deaths within 12 weeks was 24%; 81% of the
      deceased were > or = 60 years of age. Non-endocarditis patients with peripheral
      septic metastases had good prognosis. An active monitoring for metastatic
      complications in S. aureus septicemia is a necessary prerequisite for optimizing
      treatment and to improve survival rate.

PMID- 10879636
TI  - Limited sequence heterogeneity of Epstein-Barr virus nuclear antigen 1 in benign
      and malignant EBV-associated disorders.
AB  - BACKGROUND: The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is essential
      for replication and maintenance of circular EBV genomes in latently infected B
      lymphocytes and is the only EBV protein expressed in nearly all cells carrying
      the virus. EBNA-1 is suggested to be oncogenic in vivo since its expression
      induces B-cell neoplasia in transgenic mice. PATIENTS, MATERIALS AND METHODS: EBV
      wild-type isolates from ten malignant tumors and from 15 children with various
      benign EBV-associated disorders were examined for the presence of EBNA-1 variant
      strains by PCR and sequencing. RESULTS: One isolate harbored both the B95-8-like
      and a variant sequence within the C-terminus of the EBNA-1 gene. All other
      isolates (n = 24) revealed clustered nucleic acid sequence alterations within the
      EBNA-1 gene, which led to amino acid exchanges at positions 524, 563, 574, 585,
      594 and 595. Few isolates exhibited additional amino acid exchanges at positions
      564, 571 or 588. CONCLUSIONS: The observed EBNA-1 sequence variation pattern
      seems not to be restricted to a certain EBV-associated disease or tumor type. The
      EBNA-1 variant strains reported here may reflect the most prevalent EBV strains
      in the exposed population. In none of all the cases studied so far did the
      sequence alteration affect any known functionally crucial amino acids in the core
      domain of EBNA-1. This suggests that strict conservation of most of the C
      terminal portion of EBNA-1 sequence may be essential for survival of EBV in the
      infected host.

PMID- 10879637
TI  - Cerebrospinal fluid antibodies directed against neuron-associated gangliosides in
      HIV-1 infection.
AB  - BACKGROUND: Loss of synapses and neurons is a common finding in HIV-1 infection.
      Since the in vivo infection of neurons by HIV-1 is limited, indirect factors are
      likely to contribute to the pathogenesis. PATIENTS AND METHODS: We have analyzed
      cerebrospinal fluid (CSF) and serum samples from 25 HIV-1-infected individuals
      (nine with and 16 without CNS complications) and 19 HIV-negative controls with
      aseptic meningitis or viral encephalitis, for the presence of antibodies directed
      against the neuron-associated gangliosides GM1, GD1a and GD1b. RESULTS: Positive
      antibody titers to > or =1 of the gangliosides were found in 13/25 HIV-1-infected
      patients in CSF and in 17/25 in serum. Significant correlations were found
      between the presence and titers of CSF antibodies against GM1, GD1a, and GD1b.
      Six out of nine patients with, and 3/16 without neurological complications (p <
      0.05) had positive CSF titers of > or = 1 of the ganglioside antibodies combined
      with negative serum titers, indicating intrathecal antibody production. In
      contrast, only 1/19 controls had detectable anti-ganglioside antibodies in the
      CSF. CONCLUSION: The results should be interpreted with caution and CSF anti
      ganglioside antibody production might be a part of a non-specific intrathecal
      polyclonal immunoactivation. Nevertheless, autoantibodies directed against neuron
      associated gangliosides might be involved in the neuropathogenesis in HIV-1
      disease.

PMID- 10879638
TI  - Comparison of topical 0.3% ofloxacin to fortified tobramycin-cefazolin in the
      therapy of bacterial keratitis.
AB  - BACKGROUND: In this study we compared topical ofloxacin with a combination of
      fortified tobramycin sulphate and cefazolin sodium solutions in the treatment of
      culture-proved bacterial keratitis. METHODS: 30 eyes of culture-proved bacterial
      corneal ulcers of moderate severity were included in a prospective randomized,
      controlled, double-masked study for comparison. The cases were randomly allocated
      to treatment with 0.3% ofloxacin solution (Group I) and combination of fortified
      antibiotics (1.5% tobramycin and 5% cefazolin solutions--Group II as control)
      along with supportive cycloplegic, vitamins and antiglaucoma therapy. Time for
      healing of ulcer and subjective symptoms were main outcome measures. Student's t
      test was used to compare the results. RESULTS: Staphylococcus aureus and
      coagulase-negative staphylococci were the two most common organisms isolated.
      Resolution of the ulcer was achieved in 93% and 87% in the treated and the
      control group, respectively. The mean duration of symptomatic relief was 7.8 +/-
      1.54 days in the treated group and 8.33 +/- 1.44 days in the control group; for
      epithelial healing it was 15.0 +/- 3.86 days in the treated group and 15.46 +/-
      3.86 days in the control group. Post resolution the best corrected visual acuity
      of 20/200 or better was achieved in all but one eye each in both groups.
      CONCLUSIONS: Both ofloxacin 0.3% and combined fortified tobramycin 1.5% and
      cefazolin 5% topical drops were comparable for treating cases of bacterial
      corneal ulcer of moderate severity. However, considering the easy availability
      and cost effectiveness of ofloxacin, a monotherapy with ofloxacin may be
      preferred over the combined, fortified tobramycin and cefazolin therapy.

PMID- 10879639
TI  - Comparison of azithromycin and doxycycline in the treatment of erythema migrans.
AB  - BACKGROUND: A randomized, multicenter, open clinical trial was undertaken in
      order to compare the efficacies of azithromycin and doxycycline in the treatment
      of patients with Lyme disease associated with erythema migrans. PATIENTS AND
      METHODS: A total of 48 patients was treated orally with azithromycin, 500 mg bid
      on the 1st day, followed by 500 mg once daily for the next 4 days or doxycycline
      (40 patients) 100 mg bid for 14 days. RESULTS: Intention-to-treat analysis of
      clinical efficacy showed no difference between the two treatment regimens.
      Clinical success was observed in 46 (95.8%) azithromycin- and 33 (82.5%)
      doxycycline-treated patients, (p = 0.0731). Minor symptoms persisted or appeared
      in the posttreatment period in two of 47 azithromycin- and three of 35
      doxycycline-treated patients (p = 0.646). Major manifestations appeared only in
      two patients in the doxycycline group (p = 0.179). There was no difference in the
      tolerability of both drugs. CONCLUSION: Azithromycin (a total dose of 3 g) is
      equally effective as standard doxycycline treatment for erythema migrans in adult
      patients.

PMID- 10879640
TI  - Six different strains of Neisseria meningitidis in a case with meningococcal
      sepsis and five contact persons in a boys' home.
AB  - BACKGROUND: It is routine practice to provide chemoprophylaxis for close contacts
      of a patient infected with meningococci. PATIENTS: When a 17-year-old boy living
      in a boys' home was admitted to the hospital with septic shock caused by
      Neisseria meningitidis, we immediately identified contact persons in the boys'
      home. RESULTS: 104 contact persons were identified and screened for oropharyngeal
      colonization. 77 persons received chemoprophylaxis. N. meningitidis was isolated
      from the index case and from five of 104 throat swabs of the contact persons
      (three home dwellers, one staff member, one visitor). The overall carrier rate
      was 4.8%. All isolates showed different patterns when analyzed by pulsed-field
      gel electrophoresis, which was in accordance with results of serotyping by the
      German National Reference Center for Meningococci. CONCLUSION: In this non
      epidemic situation, contacts between the index case, home mates, home personnel,
      and visitors were not close enough for effective transmission of meningococci,
      since no strain was found twice. This supports recommendations for the use of
      chemoprophylaxis in persons with intimate contact to the index patient.

PMID- 10879641
TI  - Acute hepatitis B in Western Sweden--genotypes and transmission routes.
AB  - A retrospective study of acute hepatitis B (AHB) during 1995-1996 in Goteborg,
      Sweden, was carried out to investigate whether the increasing number of hepatitis
      B virus (HBV) carriers due to immigration in northwestern Europe has influenced
      the incidence or genotype heterogenicity. 24 cases of AHB were identified, the
      probable transmission route of which was intravenous drug use (IVDU) in 11 (46%),
      heterosexual in six (25%), homosexual in one, hemodialysis in two and unknown in
      four cases. In no case was the source an immigrant with chronic HBV infection.
      Genotype D was seen in 12 patients, seven being anti-HCV-positive IVD users, two
      probably infected heterosexually and three with an unknown source. Genotype A was
      found in six patients: three IVD users, a sexual partner of an IVD user and two
      dialysis patients. Genotype B was found in one patient infected during travel to
      Vietnam, and genotype C in one patient, probably infected sexually from a
      previously identified chronic carrier. In conclusion, genotype D is the main
      genotype and IVDU still the major risk factor for AHB in Goteborg, while
      transmission from immigrants appears to be of minor importance despite the fact
      that this group comprises over 90% of the young, highly infectious carriers.

PMID- 10879642
TI  - The Erve virus: possible mode of transmission and reservoir.
AB  - The Erve virus is suspected to cause severe headache in humans, lasting several
      days (thunderclap headache). Mice are characterized as a probable reservoir for
      the Erve virus. We tested 396 wild mice for Erve virus using an
      immunofluorescence test and found Erve virus antibodies in five cases, showing
      that small mammals form a reservoir for Erve virus. If ticks are the vector for
      the virus, a coincidence with borreliosis should exist. We were unable to confirm
      this in a homogeneous cohort of 955 young men, 62 of whom tested positive for
      borreliosis. This group did not test positive significantly more often in the
      immunofluorescence test than a gender- and age-matched control group.

PMID- 10879643
TI  - First-line nevirapine in combination with nucleoside analogues compared with
      nevirapine added to a salvage HAART.
AB  - BACKGROUND: Although non-nucleoside reverse transcriptase inhibitors are
      presently recommended as a part of an initial triple antiretroviral regimen, or
      as an adjunct to a rescue therapy in patients with poor response to highly active
      antiretroviral therapy (HAART), no controlled data are available comparing these
      two different strategies of administration of nevirapine. PATIENTS AND METHODS:
      Laboratorys data of 59 consecutive patients were prospectively followed up to
      compare the virologic and immunologic response to nevirapine in those starting a
      triple therapy combination (group A), versus subjects with prior HAART failure
      (group B). Laboratory data of 59 consecutive were prospectively followed up.
      RESULTS: In group A (33 cases), nevirapine was started with two nucleoside
      analogues in six subjects naive to antiretrovirals, while in 27 cases it was
      added to a novel combination of nucleoside analogues. In group B (26 cases),
      highly experienced patients failing a protease inhibitor-containing HAART, were
      given nevirapine concurrently with nelfinavir in 19 cases, and with two protease
      inhibitors in seven patients. Compared with group B patients, subjects belonging
      to group A showed a more favorable 9-month virologic response (-2.2 Log10 after 9
      months with two thirds of patients attaining viral suppression, versus -0.8 Log10
      in group A, with only 34.6% of patients with undetectable viremia) (p < 0.001). A
      greater rise of mean absolute CD4+ lymphocyte count was also observed in group A
      as opposed to group B (p < 0.001). No significant difference was found comparing
      the laboratory response of antiretroviral-naive versus -experienced patients, as
      well as of participants who changed one versus both nucleoside analogues at the
      time of nevirapine adjunct in group A, and between patients who switched to
      nelfinavir versus those treated with two protease inhibitors in group B.
      CONCLUSION: Nevirapine used as a component of an initial triple anti-HIV regimen
      seems to ensure a significantly more favorable virologic and immunologic outcome,
      compared with nevirapine adjunct to a salvage regimen carried out after HAART
      failure. Controlled data are needed, to better define the role of nevirapine in
      different therapeutic situations.

PMID- 10879644
TI  - Visceral leishmaniasis and other severe infections in an adult patient with p47
      phox-deficient chronic granulomatous disease.
AB  - We report a rare case of a male patient without known immunodeficiency
      consecutively diagnosed with visceral leishmaniasis, brain abscess and cavitating
      pneumonia in the 3rd decade of life. Chronic granulomatous disease (CGD) was
      diagnosed by a nitroblue tetrazolium test. A p47-phox mutation of the NADPH
      oxidase of the leukocytes was suspected by immunoblotting and confirmed by DNA
      analysis. The patient was homozygous for this mutation while his mother and
      sister were heterozygous asymptomatic carriers. After the CGD diagnosis the
      patient started a chronic prophylactic regimen with subcutaneous interferon-gamma
      (0.05 mg/m2 of body surface/three times a week), and oral trimethoprim
      sulfamethoxazole and itraconazole (both at 5 mg/kg/day) with no subsequent
      infections after 12 months of follow-up.

PMID- 10879645
TI  - Pneumococcal cellulitis in an HIV-infected adult.
AB  - Streptococcus pneumoniae is an uncommon cause of cellulitis. In almost all of the
      reported cases, the infection occurred in immunosuppressed patients, especially
      in those with connective tissue diseases. We report a case of cervical cellulitis
      associated with septicemia which occurred in an HIV-infected adult.

PMID- 10879646
TI  - Scrub typhus-associated hemophagocytic syndrome.
AB  - A patient was admitted to our hospital with fever of unknown origin,
      lymphadenopathy and moderate anemia. The diagnosis of scrub typhus (tsutsugamushi
      disease) was established on specific serologic demonstration of antibodies to the
      cross-reacting proteins OX-K antigen and reaffirmed by successful treatment with
      doxycycline. The diagnosis of hemophagocytic syndrome (HPS) was made on the
      cytologic findings of many histiocytes containing phagocytosed blood cells in the
      marrow aspirate. The hemophagocytosis phenomenon disappeared after the scrub
      typhus was successfully treated, thus suggesting the relationship between scrub
      typhus and hemophagocytosis. In a patient with rickettsial diseases including
      scrub typhus, associated with HPS, it is important to understand the relationship
      between the two disorders since the prognosis for HPS, if untreated, is very
      poor.

PMID- 10879647
TI  - Two cases of fulminant Mycoplasma pneumoniae pneumonia within 4 months.
AB  - We report the clinical course and diagnostic findings in two patients with life
      threatening Mycoplasma pneumoniae (MP) pneumonia who were treated in the same
      hospital in the course of only 4 months. The patients were previously healthy
      adults, aged 31 and 37 years, respectively. In both of them severe complications
      occurred which coincided with the acute MP respiratory infection.

PMID- 10879648
TI  - Pneumocystis carinii pneumonia in an immunocompetent infant with congenital
      cytomegalovirus infection.
AB  - The case of a term infant with congenital cytomegalovirus (CMV) infection who
      developed Pneumocystis carinii pneumonia (PCP) at 4 months of age is reported.
      Our patient suffered from severe malnutrition and zinc deficiency secondary to
      necrotizing enterocolitis since the age of 2 months. There was no evidence of
      human immunodeficiency virus infection. Qualitative and quantitative in vitro
      leukocyte functions were also normal. This case highlights the fact that PCP can
      occur in apparently immunocompetent term infants. Malnourished infants with zinc
      deficiency or congenital CMV infection are at increased risk of developing PCP.

PMID- 10879649
TI  - Extrahepatic alveolar echinococcosis without liver involvement: a rare
      manifestation.
AB  - BACKGROUND: Alveolar echinococcosis (AE) primarily affects the liver and
      extrahepatic disease is considered the consequence of a secondary infection via
      metastatic spread from the hepatic focus. PATIENTS: Two patients with
      extrahepatic AE without liver involvement are presented. The first case is a
      patient with AE of the spleen and a small pulmonary calcification. In the second
      case exclusive affection of the spine was observed. DISCUSSION: Various
      pathogenetic explanations for hepatic omission appear plausible: a passage of
      oncospheres through hepatic sinuses without causing disease, a passage via
      lymphatic vessels or via portocaval anastomoses and the vascular passage in a
      retrograde fashion. Extrahepatic manifestation of AE without apparent liver
      involvement is rare. However, AE should be taken into account among other
      differential diagnoses even in cases of extrahepatic lesions without liver
      involvement.

PMID- 10879650
TI  - Serious complications of tuberculous epididymitis.
AB  - Tuberculous epididymitis is a rare entity associated with minor complications. We
      present two cases of tuberculous epididymitis associated with serious
      complications (bilateral psoas abscesses and Addison's disease with psoas
      abscess). A review of the literature disclosed six additional cases associated
      with serious complications (Addison's disease, inappropriate antidiuretic hormone
      secretion, central nervous system involvement) which are discussed and compared
      to these cases. We conclude that tuberculous epididymitis represents a grave
      sequela of genital tract involvement and may be associated with serious and even
      fatal complications.

PMID- 10879651
TI  - Low normal potassium levels in acute renal failure: evidence of leptospirosis.

PMID- 10879652
TI  - Chimpanzees as an outgroup for the examination of human dental evolution.
AB  - In the assessment of human origins, chimpanzees (Pan troglodytes, henceforth
      called Pan) represent the best hominoid outgroup for comparisons. Such an
      outgroup roots the "anatomically modern" human population cluster, or continuum.
      This study incorporates chimpanzees into a worldwide modern human database of
      quantified complete tooth variables (approximately 30 per tooth; e.g., root,
      pulp, enamel) in an attempt to develop a more accurate phylogeny of the hominoid
      continuum, with only intervening extinct hominids missing. Canonical discriminate
      analysis was performed mainly among Liberian common chimpanzees and global
      samples of humans. The first canonical variable explained 70% of the total
      variance and showed a tight cluster of humans, with chimpanzees as a distant
      outgroup. Within the human community, first non-San Bushman, sub-Saharan Africans
      and Andamanese, and then, close in, Australian aborigines were positioned towards
      Pan. Their relative orientation suggested an African human origin with the first
      branch within sub-Saharan Africa: sub-Saharan Africans and San Bushmen. Next,
      Andamanese Negritos, and then Australian aborigines, formed the early first
      surviving modern human lineage to leave Africa. Thin enamel and big teeth with
      relatively large roots characterized Pan nonmolar teeth. Humans showed a
      generalized sexual dimorphism for all teeth, with males having bigger teeth,
      bigger relative roots, and thinner enamel than females, while only Pan canines
      had significant and impressive sexual dimorphism. Interestingly, Pan molars were
      not larger than human molars. The data suggest that although hominids underwent
      two dental macroevolutionary events, the lineage leading to modern humans only
      experienced anterior tooth-size reduction. The suggested evolutionary
      significance of the observed total tooth variation is discussed.

PMID- 10879653
TI  - Midfacial morphology of Koreans with class III malocclusions investigated with
      finite-element scaling analysis.
AB  - The spheno-ethmoidal model of midfacial retrognathia suggests that deficient
      chondrocytic proliferation in the anterior cranial base is associated with
      inadequate anterior translation of the midfacial complex resulting, for example,
      in Class III malocclusions. The purpose of this study was to determine whether
      the morphology of the midface differed in subjects of diverse ethnic origin
      exhibiting features associated with Class III malocclusions. Lateral
      cephalographs of 142 children of Korean or European American descent aged between
      5 and 11 years were compared. The cephalographs were traced and subdivided into
      seven age- and sex-matched groups. Average geometries, scaled to an equivalent
      size, were generated using Procrustes superimposition and subjected to analysis
      of variance (ANOVA). Graphical analysis using a color-coded finite-element
      scaling analysis (FESA) program was used to localize differences in morphology.
      Results indicated that the mean Korean and European American midfacial
      configurations differed statistically (P < 0.01), and this difference was
      maintained at most, but not all, age-wise comparisons. Comparing Korean and
      European American Class III midfacial configurations for local size-change, FESA
      analysis revealed that while local increases in size were apparent in the
      posterior palatal regions, the Korean anterior nasal spine regions were generally
      smaller. For shape-change, the Korean and European American midfacial
      configurations were predominantly isotropic. Therefore, heterogeneity in
      appearance may be influenced by morphological variation of the midfacial complex
      in subjects of diverse ethnic origin, but features of the anterior cranial base
      may contribute also to the prevalence and severity of Class III malocclusions in
      Koreans. Moreover, perturbations in endochondral mechanisms of cranio-mandibular
      growth, and not maxillary intramembranous methods, may be implicated in the
      etiology of Class III malocclusions in South East Asians.

PMID- 10879654
TI  - Craniofacial disorders caused by mutations in homeobox genes MSX1 and MSX2.
AB  - The molecular biology of the homeobox genes MSX1 and MSX2 is reviewed. In a
      selective type of tooth agenesis, an MSX1 G --> C transversion results in a
      missense mutation Arg31Pro. The phenotype is due to haploinsufficiency. Boston
      type craniosynostosis involves an MSX2 C --> A transversion, resulting in a
      missense mutation Pro7His. Three different mutations on MSX2 cause parietal
      foramina by haploinsufficiency. These mutations, which result in decreased
      parietal ossification, are in marked contrast to the gain-of-function mutation
      for Boston-type craniosynostosis, which results in increased sutural
      ossification.

PMID- 10879655
TI  - Expression and activity of protein kinase C isoenzymes during normal and abnormal
      murine palate development.
AB  - Protein kinase C (PKC) plays a critical role in signal transduction, mediating
      various cellular events critical for normal development, including that of the
      palate. In vivo and in vitro studies suggest the relevance of the inhibition of
      PKC by the mycotoxin, secalonic acid D (SAD), to its induction of cleft palate
      (CP) in mice. In the present study, temporal and spatial expression and the
      activity of various PKC isoenzymes were studied in the control and SAD-exposed
      murine embryonic palate during gestational days (GD) 12-14.5 by western blotting,
      immunohistochemistry, and phosphotransfer assay. The Ca2+-dependent isoenzymes,
      PKC alpha and PKC betaII, showed significant expression on GD 12.0, which
      gradually decreased through GD 14.5, whereas PKC betaI and PKC gamma were
      negligible throughout. All Ca2+-independent isoenzymes (epsilon, delta, and zeta)
      were expressed more abundantly and, in contrast to the Ca2+-dependent ones,
      progressively increased with age. SAD failed to alter this pattern of expression
      but enhanced the phosphorylation of PKC epsilon throughout development.
      Immunohistochemical analysis revealed an isoenzyme-specific distribution of PKC
      between the epithelium and mesenchyme. As expected, SAD significantly inhibited
      the total Ca2+-dependent PKC activity in palatal extracts. Although total Ca2+
      independent PKC activity in palatal extracts was unaffected by SAD, individual
      pure isoenzymes were either selectively inhibited (PKC zeta), stimulated (PKC
      delta), or unaffected (PKC epsilon) by SAD. These results show that PKC
      isoenzymes exhibit dynamic temporal and spatial patterns of expression and
      activity in the developing palate and that the induction of CP by SAD is
      associated with an alteration in their activation and/or activity.

PMID- 10879656
TI  - Position and growth of upper and lower tooth primordia in prenatal mouse--3D
      study.
AB  - The secondary palate formation in mouse has been associated with the period of
      fast growth of the mandible from embryonic days (ED) 13.0 to 16.0. During that
      time, the incisors and first molars develop from the bud to the bell stage. We
      investigated the position and growth of the tooth during prenatal elongation of
      the lower and upper jaws, and searched for the developmental stage when alignment
      of opposing teeth was achieved. Computer-aided 3D representations allowed us to
      represent the position of incisors and molars in the embryonic head from ED 13.5
      to 18.0 on the basis of data obtained from histological sections. The atlas
      hypophysis connection exhibited minimum change in length and orientation during
      the prenatal period, and thus was used as a reference line. The length of the
      teeth was calculated from 3D data. The upper first and second molars were longer
      than the lower ones. When viewed from the upper side, the upper and lower molar
      primordia were parallel from ED 13.5 to 15.0. During this period, the upper
      molars had a more lateral position than the lower ones. This situation was
      maintained in the anterior extremity of the first molars at later stages, while
      the posterior part of the upper and lower molar epithelia reached opposition in
      the medio-lateral direction from ED 16.0. The lower incisors exhibited an
      apparently backward position when compared to the upper incisors at earlier
      stages. However, the distance between the prospective anterior tips of the
      opposing incisors gradually decreased. The part of Meckel's cartilage associated
      with the lower dental quadrant elongated more than 3-fold from ED 13.5 to 18.0,
      and the lower jaw grew faster than the upper one. This difference resulted from
      the fast growth of the lower diastema from ED 14.0 to 18.0. The different growth
      speeds of the upper and lower jaws did not change the relative antero-posterior
      adjustment of the upper and lower molars, but contributed to achieving the
      opposition of the gnawing ends of the incisors.

PMID- 10879657
TI  - Action of ethanol on different skull and brain parameters in the chick embryo.
AB  - Fifty microliters of ethanol diluted in 50 microl of distilled water were
      injected into the air chamber of chick eggs immediately before their incubation,
      and modifications in a series of parameters were recorded. The somatic weight of
      the ethanol-treated embryos was lower compared with control and vehicle
      administered embryos during days 13, 15, 17, and 19 of incubation, but was the
      same on day 21. The brain weight was lower in the ethanol-treated embryos on all
      the days studied (days 13, 15, 17, 19, and 21 of incubation). Skull measurements
      showed that the transverse anteroposterior and sagittal diameters were
      significantly smaller in ethanol-treated embryos compared with control and
      vehicle-administered embryos on days 17, 19, and 21 of incubation.

PMID- 10879659
TI  - The present and the future of APD. Automated Peritoneal Dialysis.

PMID- 10879658
TI  - New biomaterials and methods for craniofacial bone defect: chondroid bone grafts
      in maxillary alveolar clefts.
AB  - The purpose of this study was to evaluate autogenous osteogenic marrow within
      chondroid bone grafts in simulated alveolar defects of mice in order to determine
      the ability of the graft material to effectively close the cleft from an osseous
      standpoint and to observe the effect of the grafting procedure. Critical-sized
      defects were made in the premaxillary bones of male mice using a surgical
      trephine and a low-speed dental engine as a model of the maxillary alveolar cleft
      for testing bone-inductive agents. Premaxillary trephine defects were not
      repaired by fibrous tissue or bone formation 30 days after operation. This
      nonhealing bony wound of the premaxilla in mice may be useful as a model for
      studying the effect of bone-inductive agents on the healing of alveolar clefts.
      Distraction osteogenesis is a recently advanced principle of bone lengthening in
      which a long bone separated by osteotomy is subjected to slow progressive
      distraction using an external fixation device. The osteotomy site was surrounded
      by an external callus consisting of hyaline cartilage. The callus contained a lot
      of chondroid bone. The transplant bone within chondroid bone was characterized by
      bone formation and remodeling 30 days after transplantation. Throughout the
      experiment, our findings demonstrated, for the first time, that the transplant
      bone that contains chondroid bone may be used clinically in relation to
      craniofacial bone defects to improve the treatment of bone grafts.

PMID- 10879660
TI  - Diagnosis and treatment of AL amyloidosis.
AB  - AL (amyloid light-chain) amyloidosis is a plasma cell disorder in which
      depositions of amyloid light-chain protein cause progressive organ failure.
      Virtually all patients with AL amyloidosis have a monoclonal protein in the serum
      or urine or a monoclonal population of plasma cells in the bone marrow. The most
      common target organ is the kidney and renal amyloidosis manifests as proteinuria
      or nephrotic syndrome in 3/4 of the patients. The median survival is one to two
      years. It is important to recognize that the amyloidosis is a dynamic process,
      and chemotherapy induced reduction of the activity of the plasma cell clone
      reduces the supply of the amyloid precursor protein and can result in a major
      regression of the deposits. Amyloid-related nephrotic syndrome and renal failure
      are potentially reversible. Conventional-dose melphalan as standard treatment can
      prolong the median duration of survival about 10 months, but the clinical
      response rates with improvement of impaired organ function are low with a slow
      response. Upfront high-dose chemotherapy with autologous peripheral blood stem
      cell transplantation is much more effective and can result in a major improvement
      of the patient's clinical condition, but the treatment-related toxicity can be
      relevant due to impaired organ function. The initial use of a conventional-dose
      chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD) to
      achieve a remission and subsequent high-dose chemotherapy is the concept of a
      German trial. The improvement of the condition of the patient by this approach
      may increase the tolerability of high-dose chemotherapy and reduce
      transplantation-related problems.

PMID- 10879661
TI  - Complement activation in nephropathia epidemica caused by Puumala hantavirus.
AB  - BACKGROUND AND AIM: Nephropathia epidemica (NE) is a hemorrhagic fever with renal
      syndrome caused by Puumala hantavirus. There is considerable variability in the
      clinical severity of NE. Its pathogenesis is largely unknown and data on
      complement activation in NE are scant. We sought here to establish how the
      complement system behaves during NE and whether the variation in the clinical
      outcome is related to the activation of complement. PATIENTS AND METHODS: The
      complement component levels and complement activation products and the clinical
      course of 25 hospital-treated acutely ill NE patients were studied. RESULTS:
      Complement activation was observed in 23 patients. In 10 patients the complement
      system was activated mainly through the alternative route, in 6 mainly through
      the classical route and in 5 through both the alternative and the classical
      route. An elevated soluble terminal complex SC5b-9 was the most sensitive
      indicator of complement activation (17 out of 25 patients). Two patients had only
      an elevated SC5b-9 value and 2 had no complement activation. The C4d/C4 maximal
      ratio was significantly higher in patients with clinically severe NE compared to
      the mild or moderate disease groups. CONCLUSION: Our results show that complement
      activation is common in NE. Although both pathways are usually activated, the
      classical pathway activation by immune complexes or directly by viral components
      is associated with a severe clinical course of NE.

PMID- 10879662
TI  - Enalapril: antiproteinuric effect in children with nephrotic syndrome.
AB  - AIM: The present study was designed to establish the antiproteinuric effect of
      ACE-I (enalapril). PATIENTS AND METHODS: Six children with steroid-resistant
      nephrotic syndrome (SRNS) and one patient affected by Alport syndrome and
      nephrotic-range proteinuria received enalapril (mean dose 0.3 mg/kg/day) during a
      mean period of 2 years. Before initiation of therapy, blood pressure was normal
      in all but one patient, the latter showed normal values with enalapril treatment.
      RESULTS: Five patients showed a significant increase of albumin levels after the
      treatment. Creatinine clearance remained stable during the study in all but one
      patient affected by Alport syndrome. CONCLUSION: In five patients (71.4%)
      enalapril therapy resulted in an important reduction ofproteinuria, in one
      patient the treatment was stopped after one year for relapse. In patient with
      Alport syndrome the fall in creatinine clearance, may simply reflect the natural
      course of the disease.

PMID- 10879663
TI  - Prediction of pregnancy outcome in subgroups of women with renal disease.
AB  - BACKGROUND: The preconception and intraconception parameters that are relevant to
      outcome in women with underlying renal disease remain controversial. SUBJECTS,
      MATERIALS AND METHODS: We analyzed the types and frequencies of short- and long
      term (2 years after delivery) maternal and neonatal complications in 38 patients
      with primary renal disease (46 pregnancies), 24 IDDM patients with diabetic
      nephropathy (24 pregnancies), and 27 patients with a functioning renal allograft
      (42 pregnancies), most of them with mild renal insufficiency. Logistic regression
      models were formulated to predict successful outcome. RESULTS: Successful
      pregnancy outcome (live, healthy infant without severe handicap 2 years after
      delivery) was observed in 98% of the patients with primary renal disease, 96% of
      the IDDM patients with diabetic nephropathy, and 89% of the patients with a
      functioning renal allograft. Factors found to be significantly predictive of
      successful outcome were absence of preexisting hypertension in all groups, in
      addition to low preconception serum uric acid level in the primary renal disease
      patients, and long interval from transplantation to conception and use of a low
      dose ofprednisone in the renal transplant patients. CONCLUSION: Most women with
      different subtypes of renal disease have a successful pregnancy outcome with
      proper prenatal care. Worse pregnancy outcome was observed in women with moderate
      or severe renal failure. Fitted logistic models may provide useful guidelines for
      counseling women with preexisting renal disease about their prospects for a
      successful pregnancy in terms of immediate and long-term maternal and neonatal
      outcome.

PMID- 10879664
TI  - Cerebral ischemia as a causative mechanism for rapid progression of brain atrophy
      in chronic hemodialysis patients.
AB  - BACKGROUND: It has been found that brain atrophy develops more rapidly in
      patients with end-stage renal failure after initiation of dialysis therapy. The
      present study was designed to analyze the relationship between brain atrophy and
      asymptomatic ischemic brain lesions. PATIENTS AND METHODS: Magnetic resonance
      imaging (MRI) was performed for the evaluation of brain atrophy and ischemic
      lesions. Brain atrophy was assessed by the ventricular-brain ratio (VBR),
      calculated as the ratio of the ventricular area to the whole brain area on the
      maximum MRI slice. The severity of periventricular hyperintensity (PVH) and the
      number of lacunae were also regarded as ischemic brain lesions. Fifty-five
      patients undergoing maintenance hemodialysis (HD) without clinically overt
      neurological signs and symptoms, with a mean age of 52 +/- 11 (SD) years and a
      mean HD duration of 7 +/- 6 (SD) years were subjected. VBR and its relationship
      to ischemic brain lesion data were compared to those in 35 non-HD patients
      (controls), with a mean age of 42 +/- 14 (SD) years. RESULTS: The VBR, the number
      of lacunae and the severity of PVH tended to increase with age in HD. The VBRs at
      all age groups were significantly higher in HD than in controls (7.0 vs 3.7% at
      the 4th decade, p < 0.05; 8.4 vs 5. 9% at the 5th decade, p < 0.05; 9.6 vs 5.4%
      at the 6th decade, p < 0.05; and 11.6 vs 6.3% at the 7th decade, p < 0.05). HD
      patients had significantly higher number of lacunae and had more advanced PVH
      than did controls. Both the number of lacunae and the severity of PVH were
      significantly correlated to VBR in HD. CONCLUSION: In conclusion, the rapid
      progression of brain atrophy was related to the asymptomatic ischemic brain
      lesions in our HD patients. Such data indicated that cerebral ischemia might be a
      causative mechanism of brain atrophy in chronic hemodialysis patients.

PMID- 10879665
TI  - Effect of the hemodialysis membrane on the inflammatory reaction in vivo.
AB  - BACKGROUND: Increased levels of C-reactive protein (CRP), a marker of systemic
      inflammation, are associated with myocardial infarction, stroke and the
      development of peripheral arterial disease. Hemodialysis patients show signs of
      an inflammatory reaction indicated by elevated plasma levels of CRP and by
      increased plasma levels of interleukins. PATIENTS AND METHODS: To investigate the
      effect of the dialysis membrane on the inflammatory reaction, we conducted a
      randomized study in 18 hemodialysis patients. Patients were subsequently treated
      with dialyzers containing polyamide, polycarbonate or cuprophan for 8 weeks on
      each dialyzer in a crossover design. During each treatment period, CRP plasma
      levels were measured 6 times at weekly intervals. The total content and the
      spontaneous and lipopolysaccharide- (LPS) stimulated production of interleukin
      1beta (IL-1beta), IL-6 and IL-1 receptor antagonist (IL-1Ra) were determined in
      whole blood samples. RESULTS: CRP plasma levels were significantly higher in
      hemodialysis patients (all patients, 1.63 +/- 0.23 mg/dl) compared to normals
      (0.14 +/- 0.02 mg/dl, p < 0.0001). CRP levels were lower when patients were
      dialyzed with polyamide (1.19 +/- 0.18 mg/dl) compared to the levels when the
      same patients were dialyzed with cuprophan (1.77 +/- 0.37 mg/dl, p = 0.02) or
      with polycarbonate (1.34 +/- 0.2 mg/dl, n.s). The whole blood content of IL-1Ra
      in non-incubated samples was significantly lower in normal subjects (512 +/- 60
      pg/ml) compared to hemodialysis patients (980 +/- 80 pg/ml, p < 0.01). The whole
      blood content of IL-1Ra was higher when patients were dialyzed with cuprophan
      (1,062 +/- 119 pg/ml) compared to the same patients on polyamide (906 +/- 78
      pg/ml, p < 0.05) or on polycarbonate (973 +/- 80 pg/ml, n.s.). Spontaneous and
      LPS-induced production of IL-1beta and IL-6 was similar for all dialyzers.
      CONCLUSION: We conclude that the inflammatory reaction in hemodialysis patients
      is affected by the choice of the dialyzer.

PMID- 10879666
TI  - Sleep-apnea in patients with end-stage renal disease and objective results.
AB  - BACKGROUND: A high prevalence of sleep apnea syndrome (SAS) of 54%-80% has been
      reported in patients with end-stage renal disease (ESRD). However, these studies
      were either done in highly selected small patient groups or without objective
      data using questionnaires only. PATIENTS AND METHODS: We, therefore, studied the
      prevalence of SAS in a large, unselected group of patients with ESRD. During a 6
      month period 77 out of 84 unselected patients with ESRD filled out the sleep
      apnea questionnaire of the University of Marburg and the Epworth Sleepiness
      Scale. In 55 of these patients, snoring sounds, heart rate, body position and
      transcapillary arterial oxygen saturation were recorded with an ambulatory device
      during the night after hemodialysis. RESULTS: In the questionnaires, 70.3% of the
      patients reported of an excessive day-time sleepiness, 40.5% of unwillingly
      falling asleep during the daytime and 35.2% rated their ability to concentrate as
      decreased. 30.9% (40% male/15% female) of the patients showed evidence of sleep
      disordered breathing with an apnea-hypopnea-index (AHI) equal or more than
      5/hour. 16.4% (20% male/10% female) of the patients met the diagnostic criteria
      of SAS. Neither dialysis and biochemical data nor anamnestic parameters measured
      by the questionnaires correlated significantly with sleep-disordered breathing.
      CONCLUSION: The prevalence of SAS in this large unselected patient group was not
      as high as previously reported, but it is still considerably higher than in the
      general population. Objective recordings are essential, as questionnaires
      overestimate the prevalence of SAS in patients with ESRD. As SAS promotes
      hypertension and impairs quality of life, ESRD patients might benefit from a
      treatment of concomitant SAS.

PMID- 10879667
TI  - Patients with renal hypouricemia with exercise-induced acute renal failure and
      chronic renal dysfunction.
AB  - We here report the case of a 38-year-old male with back pain and vomiting
      occurring after exercise. Serum creatinine level was elevated, and he was
      admitted to our hospital with diagnosis of acute renal failure (ARF). He had
      experienced similar attacks at least 4 times, including the present episode, from
      the age of 22 years. After admission, the patient was managed only by resting,
      and remission was nearly attained in about 1 month. The renal biopsy specimen
      performed on day 15 showed findings of acute tubular necrosis, thickening of the
      tubular basement membrane, and interstitial fibrosis. After remission, the serum
      uric acid level was 0.7-0.8 mg/dl, fractional excretion of uric acid was 0.63,
      and the possibility of other diseases facilitating the excretion of uric acid was
      denied. Therefore, ARF associated with idiopathic renal hypouricemia was
      diagnosed. Since only mild responses were observed in a pyradinamide loading test
      and a benzbromarone loading test, the case was considered to be a presecretary
      reabsorption disorder type. Renal function tests showed the almost complete
      recovery of the glomerular filtration rate (GFR: 114 ml/min/1.73 m2), but the
      urine concentrating ability was markedly decreased (specific gravity 1.019 and
      osmolarity 516 mOsm/kgxH2O in Fishberg test). Past data from this patient
      indicated that this renal dysfunction had been persisting for ten years. We
      examined 9 patients with renal hypouricemia and focused on the differences
      between the two groups (with or without complications). Four patients had a
      history of exercise-induced ARF or calculus. The urine concentrating ability was
      significantly lower in these patients (group A) than in the other patients
      without complications (group B). The glomerular filtration rate in group A was
      within the normal range, but was lower than in group B. These results suggested
      the possibility that patients with renal hypouricemia with complications may have
      chronic renal dysfunction in the future.

PMID- 10879668
TI  - The effect of vanadium-contaminated commercially available albumin solutions on
      renal tubular function.
AB  - We report our findings in a patient with coronary heart disease who received an
      intravenous albumin solution that contained a significant level of vanadium on
      the first day after elective primary coronary revascularization. Six patients who
      underwent similar surgical procedures without albumin infusion were taken as a
      control group. After administration of the V-contaminated albumin solution, the
      urinary excretion rates of alpha-glutathione S-transferase, a marker of proximal
      tubular damage, showed a several-fold elevation above the reference value, and
      the mean excretion rate was significantly different from that of the control
      group (p < 0.05). pi-Glutathione S-transferase, a marker of distal tubular
      damage, only marginally exceeded the upper reference limit in two urine samples
      from this patient. In all urine samples from the control group the excretion
      rates of pi-GST were below the detection limit. No significant differences in the
      excretion rates of alpha1-microglobulin and N-acetyl-beta-D-glucosaminidase were
      found between the patient treated with the albumin infusion and the patients of
      the control group. The biological half-life of intravenously administered V was
      approximately 125 h. All commercially available albumin solutions contain traces
      of vanadium with the concentration varying between 1.1 and 677 microg/l. The free
      V fraction in the albumin solutions increased with total V concentration, the
      highest concentration of free V found being 299 microg/l. The data suggest that
      the use of albumin solutions containing high levels of vanadium can lead to renal
      injuries, especially in patients with existing impaired renal function, as is the
      case with extracorporal circulation. The contamination is believed to be a result
      of the commercial isolation process.

PMID- 10879669
TI  - A case of normotensive scleroderma renal crisis after high-dose
      methylprednisolone treatment.
AB  - A 68-year-old male was admitted for interstitial pneumonia associated with
      scleroderma. High-dose methylprednisolone was administered for treatment of the
      pneumonitis. Two weeks later, anemia, thrombocytopenia and progressive increase
      in BUN, creatinine and LDH were observed. Although the blood pressure remained
      normotensive, renal biopsy showed thrombosis of the polar arterioles and
      glomerular capillaries. The affected interlobular artery included concentric
      intimal thickening and thrombosis in the lumen. Our findings suggested that the
      antecedent use of high-dose corticosteroids is involved in precipitating
      normotensive renal crisis. Corticosteroids should be used in low doses and with
      great caution in scleroderma patients.

PMID- 10879670
TI  - Recurrence of Arthrotec-associated nephrotic syndrome with re-challenge.

PMID- 10879671
TI  - Extracorporal therapy with AN69 membranes in combination with ACE inhibition
      causing severe anaphylactoid reactions: still a current problem?
AB  - The negatively charged membrane AN69 is known to evoke anaphylactoid reactions
      both without and with concomitant ACE inhibition. Underlying reasons are mainly
      the induction of bradykinin release due to the negatively charged membrane and
      the reduced degradation of bradykinin due to ACE inhibition. This complication
      has been reported repeatedly, but anaphylactoid reactions still occur in clinical
      practice. We recently had to treat two patients who suffered anaphylactoid
      reactions during extracorporal therapy with an AN69 membrane and simultaneous ACE
      inhibition. The first incident occurred in a patient on hemodialysis, the second
      was in a patient on continuous venovenous hemofiltration. An anaphylactoid
      reaction induced by an AN69 membrane during continuous, extracorporal treatment
      in combination with ACE inhibition has not been reported so far. Our report
      intends to serve as a reminder that the potentially lethal combination of AN69
      membranes with ACE inhibitor treatment should be avoided.

PMID- 10879672
TI  - Tumoral calcinosis in uremic patients: a reply to Dietl et al.

PMID- 10879674
TI  - RPA position on quality care at the end of life. Renal Physicians Association.

PMID- 10879673
TI  - Remarks on the calculation of water deficit in patients with severe
      hypernatremia.

PMID- 10879675
TI  - Interactions between leptin and NPY affecting lipid mobilization in adipose
      tissue.
AB  - Lipid turnover and deposition is under the control of developmental, nutritional,
      metabolic and neuroendocrine influences. The aim of the current investigations
      was focused on the study of the involvement of leptin and neuropeptide Y in lipid
      mobilization. The lipolytic rate was assessed through glycerol release after
      incubation with leptin and NPY at concentrations ranging from 10(-6) to 10(-12) M
      in isolated adipocytes obtained from female rats. The presence of leptin at
      concentrations of 10(-12) to 10(-7) M in the incubation medium of isolated fat
      cells significantly increased (p < 0.0001) glycerol release, except at the
      concentration of 10(-11) M, where the increase was (p < 0.01) as compared to the
      basal lipolytic activity. On the other hand, isolated fat cells of Wistar rats
      bathed in 10(-10) to 10(-6) M concentrations of NPY demonstrated a statistically
      significant decrease (p < 0.0001) in glycerol release. At equimolar
      concentrations of leptin and NPY (10(-12) to 10(-6) M) the observed lipolytic
      activity is comparable to the basal lipolytic activity, except at a concentration
      of 10(-9) M where upon a significant increase in lipolysis is observed. A further
      increase in the equimolar concentrations, beyond 10(-9) M results in a return to
      the basal lipolytic activity. Summing up, new evidence suggests that NPY and
      leptin may interact in a homeostatic loop to regulate body-fat mass and energy
      balance not only at the central nervous system level, but also directly at the
      adipocyte level.

PMID- 10879676
TI  - Feed intake and protein skeletal muscle in growing mice treated with growth
      hormone: time course effects.
AB  - The exogenous recombinant human growth hormone (rhGH) administration on
      gastrocnemius muscle growth performance and its contribution to body growth of
      male and female BALB/c mice fed a 12 % protein diet from 25 to 50 days of age, as
      well as the mechanism of utilization of feed intake to the lean muscle deposition
      were studied. Male and female weaning mice (21 days of age) were injected
      subcutaneously for 29 days with rhGH (74 ng x g(-1)) or saline vehicle (control).
      Feed intake and body weight (BW) were measured daily. At 25, 30, 35, 40, 45 and
      50 days of age twenty mice were killed by cervical dislocation and the
      gastrocnemius muscle was isolated, weighed and the protein content was measured.
      The rhGH administration caused a biphasic response of BW and muscle growth as a
      consequence of age-specific feed intake changes. The initial feed intake fall
      induced the allometric proportion decreases in both muscle growth versus body
      growth and protein muscle versus muscle growth. That effect was due to ineffient
      utilization of energy and protein intake on protein muscle store. Later on, the
      self-controlled increase of feed intake leads to the recovery of muscle weight to
      control values, through nutrient partitioning toward non protein tissue showing a
      compensatory muscle growth. This suggests that a higher dietary protein level
      should be necessary for promoting the protein anabolic effect of GH during
      weaning.

PMID- 10879677
TI  - The effects of acute treatment with delta9-THC on exploratory behaviour and
      memory in the rat.
AB  - The aim of the present study was to evaluate the effects of delta9
      tetrahydrocannabinol (delta9-THC) on exploratory behaviour and memory,
      independent of its locomotor suppressive effects. Dopamine (DA) and noradrenaline
      (NA) contents were determined in the areas of the brain directly related to such
      behaviours (hippocampus, striatum and amygdala). An acute dose of delta9-THC led
      to a decrease in exploratory parameters and motor activity during the holeboard
      test. The radial arm maze was used to evaluate the effects of this cannabinoid
      substance on memory. Animals treated with delta9-THC committed more errors in the
      maze test compared to control, particularly when the retention process was put to
      test. Furthermore, treatment with delta9-THC led to reduced NA contents in the
      hippocampus and increased DA contents in the amygdala, without changes in the
      striatum.

PMID- 10879678
TI  - Cytoskeleton involvement on intestinal absorption processes.
AB  - It has been recently demonstrated in the laboratory that the cytoskeletal
      inhibitor cytochalasin E has an indirect inhibitory effect on the function of the
      intestinal Na+-sugar cotransporter (SGLT1). The present work confirms that
      cytochalasin E inhibits SGLT1 activity through cytoskeleton disruption, showing
      that in anaerobic conditions (N2 bubbling), which implies low cytosolic ATP
      levels, the inhibition is not observed. As it occurs in sugar transport, the Na+
      dependent intestinal transport of phenylalanine decreases if cytochalasin E is
      present in the incubation medium. However, the activity of the brush border
      enzymes sucrase, amino peptidase N and gamma-glutamyl transferase is not affected
      by the inhibitor. These enzymes only have one transmembrane domain and the active
      center is projected to the intestinal lumen. Therefore, cytoskeleton changes that
      could modify the transmembrane enzyme segment do not alter the activity of these
      enzymes. Examination of the intestine morphology after 30 min incubation with
      cytochalasin E shows only light modifications which do not seem to explain the
      inhibitory effects of the toxin on Na+-sugar or Na+-phenylalanine cotransporters
      function. On the whole, these results indicate that the inhibition of
      cytochalasin E on galactose and phenylalanine intestinal transport is secondary
      to its action on cytoskeleton through protein structure modifications.

PMID- 10879679
TI  - Multidrug resistance increment in a human colon carcinoma cell line by
      colchicine.
AB  - The most important mechanism in drug resistance is the multidrug resistance (MDR)
      phenomenon. It is possible to select MDR cells by in vitro exposure to cytotoxic
      agents. The resistance is due to the hyperexpression of the P-glycoprotein (P-Gp)
      that take drugs out from the cells. In this study, a colchicine resistant subline
      (HCA-2/1cch) was selected from a human colon adenocarcinoma after a short period
      of drug exposure, as an in vitro model of drug resistance selection. These cells
      showed cross-resistance to other drugs, which were not present in the medium
      during selection. The relative resistance was 3.32 for colchicine, 3.15 for
      vinblastine, 2.62 for vincristine and 5.22 for mitomycin C. P-glycoprotein levels
      were assayed by flow cytometry. It was found that a significant increase of 2.35
      and 1.59 had occurred in the peak and mean channel of fluorescence, respectively,
      indicating an increment of P-glycoprotein expression in relation to the parental
      line. Moreover, verapamil (10 microg/ml) produced a partial reversion of
      multidrug resistance. The sensitisation rates were 7.41 for colchicine, 1.25 for
      vinblastine, 2.36 for vincristine and 1.17 for mitomycin C. The data obtained
      suggest that colchicine exposure period (10 weeks) and dose (0.5 microg/ml)
      assayed were sufficient to produce an increment in multidrug resistance. This
      resistance could be due to higher level of P-Gp expression.

PMID- 10879680
TI  - Nutritional value of Holothuria forskali protein and effects on serum lipid
      profile in rats.
AB  - Two groups of rats were fed on diets with protein from a marine specie holothuria
      (Holothuria forskali) or casein (for the control group) during 16 days with the
      aim of assessing the nutritional value of the holothuria protein. Several serum
      lipid levels were also determined. The results of the nutritive parameters
      indicate that except for True Digestibility (which did not differ significantly
      between the two groups) all other indicators were significantly lower for the
      holothuria fed group. HDL-cholesterol level was significantly higher in the
      holothuria fed group, while triglyceride level was lower.

PMID- 10879681
TI  - Onset and evolution of nephropathy in rats with spontaneous diabetes mellitus.
AB  - The occurrence of renal diabetic complications was studied in diabetic nonobese
      IIM/FmeSS (eSS) rats. The results were compared with eumetabolic Wistar rats
      paired by sex and age. Between 6 and 12 months of age, eSS male rats had higher
      fructosamine values and glucose intolerance as well as increasing proteinuria and
      uremia. Enhancement in water, calcium and phosphorus fractional excretion with a
      concomitant lower sodium excretion, was observed from 12 months of age on. 18-
      and 21-month-old eSS rats exhibited fasting hyperglycaemia and rising values of
      fructosamine, glucose intolerance and glycosuria. Simultaneously, a notorious
      worsening of proteinuria as well as alterations in glomerular filtration were
      verified. Optic microscopy of 12-month-old eSS rat kidneys showed areas of
      tubular dilatation with protein cylinders. In 21-month-old eSS animals, kidneys
      appeared overtly damaged. Increased capsular, glomerular and Henle's thin loop
      diameters were verified in 12- and 21-month-old eSS rats. Glomeruli showed
      diffuse hypertrophy of mesangial tissue and thickening of the basement membrane.
      Areas of markedly atrophic and dilated tubules containing acidophilic
      proteinaceous material were observed. At age of 21 months, kidneys of eumetabolic
      Wistar control rats presented foci of interstitial and pielic inflammatory
      infiltrates.

PMID- 10879683
TI  - A simple method for measurement of CD14weak CD16strong monocytes in peripheral
      blood.
AB  - Mounting evidence for the clinical significance of the CD 14weak CD16strong
      monocyte subpopulation in peripheral blood induced the demand for an efficient
      method for its determination. We propose a simple, fast, no-wash flow cytometric
      method using fluorescence-labelled anti-CD14, anti-CD16, and anti-HLA-DR
      antibodies and ammonium chloride-based erythrocyte lysis. This type of analysis
      can be performed on a standard three-colour flow cytometer. The method avoids
      interference by NK-cells and neutrophil granulocytes without defining monocytes
      by stringent light scatter criteria that might lead to a loss of CD14weak
      CD16strong monocytes. It, therefore, offers high reliability and accuracy. Its
      performance recommends the method to be used for routine clinical measurements of
      CD14weak CD16strong monocytes.

PMID- 10879682
TI  - Vascular oxidant stress: molecular mechanisms and pathophysiological
      implications.
AB  - The term oxidative stress refers to a situation in which cells are exposed to
      excessive levels of either molecular oxygen or chemical derivatives of oxygen
      (ie, reactive oxygen species). Three enzyme systems produce reactive oxygen
      species in the vascular wall: NADH/NADPH oxidase, xanthine oxidoreductase, and
      endothelial nitric oxide synthase. Among vascular reactive oxygen species
      superoxide anion plays a critical role in vascular biology because it is the
      source for many other reactive oxygen species and various vascular cell
      functions. It is currently thought that increases in oxidant stress, namely
      excessive production of superoxide anion, are involved in the pathophysiology of
      endothelial dysfunction that accompanies a number of cardiovascular risk factors
      including hypercholesterolemia, hypertension and cigarette smoking. On the other
      hand, vascular oxidant stress plays a pivotal role in the evolution of clinical
      conditions such as atherosclerosis, diabetes and heart failure.

PMID- 10879684
TI  - The M-DC8-positive leukocytes are a subpopulation of the CD14+ CD16+ monocytes.
AB  - Recently, a population of M-DC8-positive leukocytes has been described as a new
      subpopulation of human dendritic cells (DC). In view of the expression of the
      CD16 antigen on these cells, as well as the finding that DC can arise from blood
      monocytes, we hypothesized that the expression of M-DC8 is mainly associated with
      the CD14+ CD16+ phenotype of blood monocytes. Immunofluorescence analysis of
      whole blood showed that the percentage of M-DC8+ cells is about three times lower
      than the percentage of CD14+ CD16+ monocytes among all leukocytes (0.32% versus
      1.10%). Further, in addition to the expression of CD16, these M-DC8+ cells were
      also positive for CD14 at low density. Multicolor flow cytometric analysis of
      whole blood revealed that more than one third of the CD14+ CD16+ monocyte
      population expressed the M-DC8 antigen (42.3%), and almost all M-DC8+ cells were
      CD14-CD16-double-positive (87.5%). Finally, the M-DC8 antigen was also expressed
      on alveolar macrophages from healthy individuals, i.e., cells that are
      phenotypically and functionally related to the CD14+ CD16+ monocytes. Taken
      together, the data presented here clearly demonstrate that the M-DC8+ leukocytes
      are a subpopulation of the CD14+ CD16+ monocytes and may represent DC

PMID- 10879685
TI  - Proliferation of a subpopulation of human peripheral blood monocytes in the
      presence of colony stimulating factors may contribute to the inflammatory process
      in diseases such as rheumatoid arthritis.
AB  - Apart from acting on hemopoietic progenitor cells, colony stimulating factors
      (CSFs) have been shown to be involved in the activation, survival, proliferation
      and differentiation of more mature cells of the monocyte/macrophage lineage.
      There is evidence that a proportion of human peripheral blood monocytes can
      proliferate in response to CSF-1, (also known as M-CSF) and granulocyte
      macrophage-CSF (GM-CSF). CSFs have been shown to be at elevated levels in the
      synovial fluid of RA patients and thus local proliferation of monocyte/macrophage
      within an inflamed lesion may contribute to the local tissue hyperplasia evident
      in inflammatory conditions. Flow cytometric analysis of surface antigen
      expression and cytokine production in response to lipopolysaccharide stimulation
      has been used to characterise the proliferating subpopulation of monocytes.
      Further characterization and subsequent isolation of this subpopulation of
      monocytes may provide new and important information necessary in understanding
      inflammatory diseases such as rheumatoid arthritis, where local proliferation at
      the site of inflammation may be a key factor contributing to the chronicity of
      the disease.

PMID- 10879686
TI  - Elevation of CD69+ monocyte/macrophages in patients with Alzheimer's disease.
AB  - In this report, we examined the presence of the activation marker, CD69, on
      monocytes derived from patients with Alzheimer's disease (AD). We have previously
      shown that patients with AIDS dementia had an elevated percentage of a
      CD14+/CD69+ subset and that conditioned media from these M/M phi cultures were
      toxic to neural cultures. We therefore postulated that patients with AD might
      likewise have a higher monocyte subset and that this would be associated with
      neural toxicity. Flow analysis showed that AD patients (n = 13) had a higher
      percentage of CD69+ M/M phi over age matched controls (n = 14); this trend was
      statistically significant (p = 0.006). Side scatter (SSC), a measure of cellular
      granularity was also elevated in AD patients (p = 0.02). The elevated expression
      of human leukocyte antigen (HLA-DR) was not found to be significant between age
      matched controls and AD patients. When conditioned media from M/M phi from five
      AD and two control patients were evaluated for neurotoxicity, three of the five
      culture supernatants from AD patients induced apoptosis in neural cell aggregate
      cultures. Electrophoretic mobility shift assays revealed that these three
      supernatants also triggered NF-kappaB translocation to the nucleus. Surprisingly,
      in vitro neurotoxicity was induced by M/M phi supernatants having a lower
      percentage of CD14+/CD69+ cells. Elevation of the CD14+/CD69+ subset in AD
      patients may therefore represent a manifestation in the peripheral blood of the
      pathological events occurring in the brain but may not be directly involved in
      neural cell toxicity.

PMID- 10879687
TI  - The ILT family of leukocyte receptors.
AB  - In this short review we examine the recently identified immunoglobulin-like
      transcript (ILT) family of receptors (also known as LIR and MIR). ILT are
      expressed by many leukocyte subsets, especially monocytic cells. Expression
      levels of certain ILT molecules allow definition of blood monocyte and dendritic
      cell (DC) subsets. Two receptors, ILT2 and ILT4, recognise a broad range of MHC
      class I molecules and transduce an inhibitory signal. Such recognition may give
      many cell lineages the potential to recognise and respond to MHC class I down
      regulation.

PMID- 10879688
TI  - Human MO subsets as defined by expression of CD64 and CD16 differ in phagocytic
      activity and generation of oxygen intermediates.
AB  - Phagocytosis and killing of microorganisms by reactive oxygen radicals are
      important defence mechanisms of the immune system and it was shown that human
      monocytes (MO) are heterogeneous in exerting these functions. Previously, we
      described that human peripheral blood MO consist of a major subset of Fc gamma
      receptor-I (CD64)-positive cells exhibiting low accessory cell capacity but high
      phagocytic activity, and a minor subset of CD64-negative cells with dendritic
      cell (DC)-like high T cell accessory cell capacity but low phagocytic capacity.
      Recently, we could show that each subset itself further differs in the expression
      of the Fc gamma-receptor-III (CD16) and T cell accessory activities resulting in
      four different subsets: two CD16+ subsets (CD64+ or CD64-) with high T cell
      stimulation capacity and two CD16- subsets (CD64+ or CD64-) with low accessory
      activities. In the present study we demonstrate that these subsets also differ in
      their ability to phagocytose opsonized bacteria (S. aureus and E. coli) and in
      the generation of reactive oxygen species. Both CD64+ subsets (CD16+ or CD16-)
      exhibit high phagocytic activity accompanied by intracellular superoxide
      induction. Luminol-dependent (mainly myeloperoxidase (MPO)-mediated)
      chemiluminescence (CL) response to latex and FMLP
      (formylmethionylleucylphenylalanine) was also high in these cell populations.
      Phagocytic activity and modest CL response was shown in CD64-/CD16+ but not in
      CD64-/CD16- cells, indicating that each subset except for CD64-/CD16- cells may
      engulf bacteria and exhibit MPO activity. Taken together, these data demonstrate
      further heterogeneity of peripheral blood MO in both, phagocytic activity and
      generation of reactive oxygen species indicating differences between the four
      subsets in this kind of defence mechanisms against pathogens.

PMID- 10879689
TI  - Multi-color analysis of monocyte and dendritic cell precursor heterogeneity in
      whole blood.
AB  - The coexpression analysis of the 55-kDa lipopolysaccharide receptor (CD14) and
      the Fc gamma-receptor III (CD16) reveals a broad heterogeneity of blood monocytes
      which in our previous work could be divided into five subpopulations based on
      correlated differences in expression of the pan-myeloid antigen CD33 and the
      adhesion antigens CD11a, CD11b and CD56. An even larger complexity of myeloid
      cells with antigen presenting capacity in peripheral blood is suggested by the
      description of small populations of immature and mature precursors of dendritic
      cells which rapidly develop potent costimulatory activity and a dendritic
      morphology in in vitro culture. The identity of the subsets of cells which have
      been described based on heterogeneous analytical approaches, however, remains
      unclear. The goal of this study, therefore, was the correlated analysis of
      monocyte subpopulations and dendritic cell precursors in a quantitative whole
      blood assay. This was achieved based on simultaneous expression analysis of the
      monocyte markers CD14 and CD16 with antigens such as CD33, HLA-DR, the integrin
      CD11c, and the interleukin-3 receptor alpha-chain (CD123) which in absence of
      lineage-related antigens have been used for description of dendritic cell
      precursors. The selected marker panel revealed identity of cells previously
      described as CD33bright CD14dim dendritic cell precursors with CD11c+lin-HLA-DR+
      cells. Dendritic cell precursors considered to be less mature which have been
      alternatively described as CD33+ CD14dim CD16- cells or CD123hi dendritic cell
      precursors, however, were shown to differ in phenotype from each other with
      regard to expression density of CD33 and expression of CD14. In summary, our
      study revealed a complex heterogeneity of monocytes and dendritic cell precursors
      in peripheral blood and indicates that a direct comparison of the analytical
      approaches of different authors is needed to further clarify the ontogeny of
      human monocytes and dendritic cells.

PMID- 10879690
TI  - Flow cytometric analysis of different adhesion molecules expression on
      circulating CD14- and CD64- human dendritic cell precursors.
AB  - Blood dendritic cell precursors (DCps) are identified as mononuclear leukocytes
      expressing HLA-DR but lacking the characteristic antigens associated with T cells
      (CD3), NK cells (CD16 and CD56) and B cells (CD 19). Dendritic cell precursors
      are distinguished from monocytes by their lack of expression of CD64 rather than
      of CD14. This study investigated whether CD14- DCps differed from CD64-DCps,
      which were predominantly CD14+, in their expression of five well-characterised
      adhesion molecules. There were significantly fewer cells expressing CD11b, CD18
      and CD29 in the CD64-DCp population compared with CD14- DCps, and this CD64- DCp
      subpopulation also had a lower expression of CD11b and CD18. Our results suggest
      that the two DC precursor subpopulations may differ from one another in their
      binding characteristics to blood vessel walls and to other leukocytes.

PMID- 10879691
TI  - Alkaline phosphatase expression during monocyte differentiation. Overlapping
      markers as a link between monocytic cells, dendritic cells, osteoclasts and
      osteoblasts.
AB  - Human monocytes (Mo) in culture can be differentiated into macrophages (M phi),
      dendritic cells (DC) and osteoclasts. In addition, we have established a Mo
      derived in vitro granuloma model which here was compared with ex-vivo isolated
      foreign body granuloma cells. In these models overlapping phenotypes developed
      between monocyte-derived dendritic cells (MoDC), osteoclasts, M phi, and
      osteoblasts. In Mo cultures granulomas were induced by immobilized particulate
      material. AP activity (osteoblast marker) was found to be co-expressed with
      cytoplasmic tartrate resistant acid phosphatase (TRAP) as a marker of
      osteoclasts. While proliferating, the number of AP+ cells decreased, being
      replaced by cells co-expressing the osteoclast markers vitronectin receptor (VNR)
      and TRAP. Coexpression of the Mo/M phi marker CD68 with AP or VNR confirmed the
      monocytic origin of the cells. When Mo were treated with interleukin-4 (IL-4),
      the number of AP+ cells markedly increased and remained stably expressed over 12
      days. In explants from ex vivo granulomas obtained from endoprosthetic revisions
      the major cell type was the AP+ cell co-expressing CD68. The bone-specific
      alkaline phosphatase (BAP) as a marker of osteoblasts was detected by FACS
      analysis in the ex vivo granuloma cells. By RT-PCR the mRNA for osteocalcin,
      which is a highly specific marker for osteoblasts, was detected. From our results
      we conclude an ontogenetic relationship between macrophages, DC and osteoclasts.
      Furthermore, the data suggest a transdifferentiation between Mo and osteoblasts.

PMID- 10879692
TI  - Phenotypic characterization of monocyte subpopulations in the pig.
AB  - We have recently described the existence of two subsets of porcine monocytes
      based on the expression of CD163. In this study we compare the expression of a
      number of cell surface antigens in CD163+ and CD163- monocyte subsets using three
      color flow cytometry. These monocyte subsets show differences with respect to the
      expression of MHC class II antigens (SLA-DR and DQ) and a variety of adhesion
      molecules (CD11a, wCD11c, wCD29, CD49d) that are expressed at higher levels on
      CD163+ monocytes, and of CD14 that is higher expressed by CD 163- cells. These
      differences on phenotype could reflect differences in the ability of these two
      subsets to migrate to tissues and may account for the higher allostimulatory
      capacity of CD163+ cells. In some aspects, the phenotype of CD163+ monocytes
      resembles that of mature macrophages. In vitro serum-induced maturation of
      monocytes into macrophages lead to the expression of SWC9 together with an
      increase in the expression of CD163 and a reduction in that of CD14. These
      results delineate a maturation pathway where CD14hiCD163-SWC9- monocytes develop
      into CD14loCD163+SWC9- monocytes and these cells into CD14loCD163+SWC9+
      macrophages.

PMID- 10879693
TI  - Monocytes in the rat.
AB  - We review our methods for definition and phenotypical characterisation of normal
      and activated rat monocytes. To obtain a comprehensive sample of all blood
      monocytes including cells from the marginal pool of the blood stream, we
      extensively perfuse the extrapulmonary circulation with cold PBS/EDTA. Normal rat
      monocytes are isolated from untreated specified pathogen-free male LEW rats. In
      vivo activated monocytes are investigated after three days of infusion of
      recombinant IFN-gamma or during acute renal allograft rejection. Rat monocytes
      are defined by reactivity with mAbs ED1 and ED9, detecting a lysosomal membrane
      antigen and a member of the signal-regulatory protein family, respectively, as
      well as by expression of CD11b. Concomitantly rat monocytes are characterized by
      the absence of CD5, the absence of the B cell form of CD45R, and the absence of
      reactivity with mAb RP-1. The majority of the monocytes from untreated LEW rats
      are CD4+, CD11a(high), CD18high, CD43high, CD62-L-, CD161-, and MHC class II-.
      Upon stimulation of the immune system in vivo, a second monocyte population
      increases in number. These cells have a larger diameter and an increased
      granularity. They are CD4-, CD11a(int), CD18int, CD43low, CD62-L+, CD161int, and
      MHC class II+. Although some reagents are not yet available (e.g. antibodies
      against rat CD14 and CD16), rat monocytes can be defined and their state of
      activation can be characterized. The functionally important population of
      monocytes, which have already marginated, is accessible by perfusion and
      relatively high monocyte numbers are isolated per rat. As specified pathogen-free
      rats are available and numerous experimental systems involving acute or chronic
      inflammation have been established in rats, differentially activated monocytes
      may be investigated. The rat is thus a suitable experimental animal for basic
      research on monocytes.

PMID- 10879694
TI  - Static and dynamic MRI of a urinary control intra-vaginal device.
AB  - The aim of this study was to describe by MRI, in dynamic conditions at rest and
      straining, the anatomical modifications induced by a commercially available
      intravaginal device (IVD) aimed at relieving female stress urinary incontinence.
      Ten female patients complaining of stress urinary incontinence (SUI) had pelvic
      MRI with static and dynamic sequences, without and with a self-inserted IVD. We
      studied positions and angulations of the IVD in the pelvis. Paired t-test allowed
      comparisons of: position of the bladder neck; urethral angulation with the pubis
      axis; position of the urethra; and posterior urethro-vesical angle (PUVA) without
      and with IVD. At rest, in ten of ten cases IVD laid cranial to the pubo-rectal
      muscle; with an average angulation of 95 +/- 10 degrees with the pubis axis,
      laterally tilted in three of ten cases. In maximum straining with IVD bladder
      neck descent was lower by an average of 5.2 +/- 3.1 mm (p = 0.001), pubo-urethral
      angle opening was smaller by an average of 22 +/- 20 degrees (p = 0.015), and
      bladder neck to pubis distance was shorter by an average of 5.7 +/- 4 mm.
      Posterior urethro-vesical angle was not significantly modified. Dynamic MRI
      allowed a non-invasive assessment of the mode of action of an IVD. The main
      modifications were a support of the bladder base and bladder neck, with a
      superior displacement of the urethra toward the pubis.

PMID- 10879695
TI  - MR imaging features of pelvic mucinous carcinomas.
AB  - Mucinous carcinomas in the pelvis differ from non-mucinous tumors because of the
      differences in clinical outcome and imaging appearance. Mucinous rectal
      carcinomas, for example, are to be higher in stage at the time of the diagnosis
      because they are more likely to be infiltrative and show a greater tendency for
      recurrence. These factors may lead to a poorer prognosis in patients with the
      mucinous as compared with non-mucinous carcinomas. Mucinous carcinomas of all
      types typically show high signal intensity on T2-weighted MR images, and
      therefore mimic other conditions such as necrotic tumors, fluid collections,
      cysts, or liver hemangiomas. To familiarize readers with the MRI appearance, and
      to avoid pitfalls, this paper illustrates the MRI features of the mucinous
      adenocarcinomas in various pelvic organs.

PMID- 10879696
TI  - Percutaneous nephrostomy: placement under laser guidance and real-time CT
      fluoroscopy.
AB  - The purpose of this paper is to present our experience with real-time computed
      tomography (CT) fluoroscopy guided percutaneous nephrostomy (PNT) and to describe
      this technique involving puncture under laser guidance. We attempted 30
      placements in 25 patients: puncture was directed by laser guidance and placement
      of the tube was made under real time CT fluoroscopy. 25 procedures were performed
      in prone position and 5 procedures in the supine position. The time necessary for
      the procedure ranged from 10 to 45 min (mean 25 min). The average duration of CT
      fluoroscopy per placement was 49 seconds (range 7-110 s). The PNT placement was
      successful as a sole procedure including puncture and catheter placement in 24 of
      30 cases; in the remainder of cases, puncture was performed under CT guidance but
      the catheter was definitively positioned in conventional fluoroscopy. The CT
      fluoroscopy technique allows routine, efficient and safe PNT placement,
      especially when encountering difficult access to the pelvicaliceal system.

PMID- 10879697
TI  - Various radiological appearances of angiomyolipomas in the same kidney.
AB  - A 21-year-old woman with tuberous sclerosis presented with abdominal distension
      and flank pain. Imaging studies, including CT and MR imaging, revealed bilateral
      renal mass lesions, containing fat and suggesting the diagnosis of tuberous
      sclerosis. However the imaging characteristics of one of these lesions differed
      from the others with no radiologically detectable fat tissue in this solid lesion
      suggesting renal cell carcinoma. Histopathological examination of this lesion in
      the left kidney revealed an angiomyolipoma within minimal fat tissue. The
      radiological diagnosis of angiomyolipomas with minimal fat tissue remains
      difficult and the differential diagnosis is discussed.

PMID- 10879698
TI  - Bilateral xanthogranulomatous perinephritis without renal parenchymal
      involvement.
AB  - A case of isolated bilateral xanthogranulomatous perinephritis, which presented
      as a symmetrical irregular perirenal rim of soft tissue, is reported.
      Differential diagnosis and image features on ultrasound, computed tomography, and
      magnetic resonance are discussed.

PMID- 10879699
TI  - Delayed posttraumatic adrenal hematoma.
AB  - Posttraumatic adrenal hemorrhage is a frequent finding after severe abdominal
      trauma and can have important clinical implications if it is bilateral. With the
      increased use of helical CT in the evaluation of trauma patients, posttraumatic
      adrenal hematoma is more frequently diagnosed. We present the CT findings of a
      unilateral posttraumatic adrenal hemorrhage where the diagnostic findings only
      appeared in the follow-up study. We think that mild enlargement of the adrenal
      gland in a trauma patient can be an early sign of an impending adrenal
      hemorrhage.

PMID- 10879700
TI  - Intramural leiomyoma of the bladder.
AB  - Mesodermal tumors of the urinary bladder are rare and the majority of them are
      malignant. We report a case of an intramural leiomyoma of the bladder presenting
      with symptoms of a mild lower urinary tract infection. The patient was managed
      with partial cystectomy and the outcome was excellent.

PMID- 10879701
TI  - Blueberry juice used per os in upper abdominal MR imaging: composition and
      initial clinical data.
AB  - The aim of this study was to evaluate the use of a commercially available
      blueberry juice (BJ) both as a positive and negative oral contrast agent and to
      present the exact contents of paramagnetic ions. The concentration of Mn and Fe
      were determined in tinned myrtilles in syrup (atomic absorption). Nine healthy
      volunteers and 12 patients (age range 20-65 years) were examined using a 1-T MR
      scanner before and after per os administration of 430 ml of BJ. A qualitative
      analysis of signal alterations in the stomach, duodenum, and proximal small
      intestine was performed. In addition, a quantitative analysis was assessed in
      terms of signal-to-noise ratio calculation. The mean concentration (x +/- SD) of
      the ions found in the content of the three cans were 3.3 +/- 0.4 microg/g for
      iron and 20.6 +/- 2.6 microg/g for manganese. Based on the qualitative
      evaluation, signal alteration on T1-weighted images after administration of BJ
      was statistically significant in the stomach and duodenum, but not in the
      proximal small bowel. Signal alteration on T2-weighted images was not
      statistically significant in any part of the gastrointestinal tract. The
      quantitative analysis of the T1- and T2 shortening showed that BJ is efficient
      with only T1-weighted sequences, and this applied to the stomach, duodenum, and
      proximal small bowl. Blueberry juice can be used as an oral contrast agent in
      upper abdominal MR for T1-weighted imaging.

PMID- 10879702
TI  - Abdominal wall hernias: imaging with spiral CT.
AB  - Computed tomography is an accurate method of identifying the various types of
      abdominal wall hernias, especially if they are clinically occult, and of
      distinguishing them from other diseases such as hematomas, abscesses and
      neoplasia. In this study we examined the CT images of 94 patients affected by
      abdominal wall hernias observed over a period of 6 years. Computed tomography
      clearly demonstrates the anatomical site of the hernial sac, the content and any
      occlusive bowel complications due to incarceration or strangulation. Clinical
      diagnosis of external hernias is particularly difficult in obese patients or in
      those with laparotic scars. In these cases abdominal imaging is essential for a
      correct preoperative diagnosis and to determine the most effective treatment.

PMID- 10879703
TI  - CT of radiation-induced injury of the gastrointestinal tract: spectrum of
      findings with barium studies correlation.
AB  - Because of improvement in survival rate of patients with abdominal cancer,
      gastrointestinal complications following external radiation therapy are becoming
      more frequent. Thus, an increased number of patients are commonly investigated
      with imaging because of suspected radiation-induced injury of the
      gastrointestinal tract. This pictorial review highlights the spectrum of CT and
      barium study manifestations of radiation-induced injury of the gastrointestinal
      tract. The major role of CT in the evaluation and management of patients with
      radiation injury of the gastrointestinal tract is highlighted. Emphasis is placed
      on CT imaging signs that may help in distinguishing between radiation-induced
      injury and recurrent disease.

PMID- 10879704
TI  - Hemobilia, intrahepatic hematoma and acute thrombosis with cavernomatous
      transformation of the portal vein after percutaneous thermoablation of a liver
      metastasis.
AB  - A 53-year-old-man underwent US-guided percutaneous thermal ablation with a cooled
      tip needle of three liver metastases from gastric cancer. Six days later, the
      patient was re-admitted for melena, scleral jaundice, and anemia. Abdominal US
      disclosed echogenic material in the gallbladder lumen (hemobilia) and a focal
      lesion with mixed echotexture in segment III (hepatic hematoma). On day 5 portal
      cavernomatosis was diagnosed at US and confirmed by color Doppler and a helical
      CT exam. The case described emphasizes that radio-frequency interstitial
      hyperthermia may cause not only traumatic injury of the liver parenchyma but also
      thermally mediated damage of vascular structures.

PMID- 10879705
TI  - Iatrogenic dissection of the portal vein during TIPS procedure.
AB  - Dissection of the portal vein is a rare entity which has been rarely described
      during transjugular intrahepatic portosystemic shunt (TIPS) procedure. We report
      three cases of dissection during this procedure and their complications. One
      dissection was immediately treated with coaxial stents. The two others were
      complicated either by a thrombus or by a false aneurysm. In the first case a
      second parallel stent was used to treat this complication. The patient with the
      portal vein false aneurysm was transplanted 4 days after this diagnosis. Portal
      vein dissection in TIPS procedure appeared to be less rare than has been reported
      and must be considered as a potential cause of TIPS dysfunction.

PMID- 10879706
TI  - US power Doppler of hepatic angiomyolipoma with low fat content.
AB  - Hepatic angiomyolipoma (AML) is a rare tumor containing a variable amount of fat.
      Angiomyolipoma prevalently constituted by vessels can be difficult to
      differentiate from other hypervascular hepatic tumors containing a small amount
      of fat. We describe US power Doppler findings in a case of hepatic AML with
      minimal fat content.

PMID- 10879707
TI  - Gallstone ileus: CT findings.
AB  - Gallstone ileus is a rare complication of recurrent gallstone cholecystitis. The
      classic radiographic triad of small bowel obstruction, pneumobilia and ectopic
      gallstone on abdominal plain radiograph is described with CT imaging. Because of
      the better resolution of CT compared with abdominal radiography and its recent
      accession to emergency use, radiologists should be aware of CT findings of
      gallstone ileus. We report a case in which gallstone ileus was initially
      diagnosed by CT.

PMID- 10879708
TI  - Role of radiology in the diagnosis of neurosarcoidosis.
AB  - Clinical studies report a rate of 5% and autopsy results a rate of 25% of brain
      involvement in sarcoidosis. The aim of this study was to evaluate the role of
      radiology in the diagnosis of patients with neurosarcoidosis. The chest
      radiographs and MRI brain scans of 22 patients with sarcoidosis were
      retrospectively reviewed, along with the information that was provided in the
      request form and clinical charts. All patients had neurological signs and
      symptoms; 21 patients were examined with contrast enhancement. Facial nerve
      paralysis was the most common clinical manifestation identified in 10 patients. A
      wide spectrum of MR findings was noted: periventricular high-signal lesions on T2
      weighted images (46%); multiple supratentorial and infratentorial brain lesions
      (36%); solitary intra-axial mass (9%); solitary extra-axial mass (5%); and
      leptomeningeal enhancement (36%). Neurological signs and symptoms can be
      significant manifestations of sarcoidosis. Magnetic resonance imaging shows a
      wide spectrum of brain abnormalities associated with neurosarcoidosis. The
      patient's history and chest X-ray are helpful in arriving at the correct
      diagnosis, but in selected cases with isolated brain involvement biopsy may still
      be required.

PMID- 10879709
TI  - Presumed capillary telangiectasia of the pons: MRI and follow-up.
AB  - Capillary telangiectasia is a vascular abnormality primarily of the brainstem.
      The clinical relevance is unclear as is the association with clearly pathologic
      findings such as cavernous haemangioma. We report on four cases with capillary
      telangiectasia proven by follow-up and describe the imaging characteristics. T2
      abnormality was only observed in half of the patients as was the presence of a
      discernable collecting vein. Whereas two cases were incidental findings in
      neurologically normal persons and one had symptoms clearly attributable to
      lacunar stroke, one patient may have had symptoms due to the vascular abnormality
      in the pons.

PMID- 10879710
TI  - Intraventricular mass lesions of the brain.
AB  - Intraventricular tumours represent a diverse group of lesions, some of them
      infrequent, with a wide variety of radiological features. Determination of their
      precise aetiology or origin can be difficult. Nevertheless, considering patient's
      age, location within the ventricles, and some specific radiological features, the
      radiologist should be able to narrow down the differential diagnosis. This paper
      reviews the characteristic radiological appearances of the diverse
      intraventricular lesions emphasising its differential diagnosis.

PMID- 10879711
TI  - Serial MRI and MRS studies with unusual findings in Rasmussen's encephalitis.
AB  - Rasmussen's syndrome is characterized by intractable seizures and progressive
      neuropsychiatric deterioration secondary to unilateral cortical inflammation and
      tissue destruction. Diagnosis of Rasmussen's syndrome in the early phase depends
      mainly on the clinical features. Neuroimaging and histopathologic examinations
      may not be specific during this period. We report a case of Rasmussen's syndrome
      followed by serial MRI and magnetic resonance spectroscopy (MRS) studies over a 3
      to 16-month period. A healthy 6-year-old boy presented with focal motor
      seizures. An MRI study demonstrated prominent enlargement and T2 hyperintensity
      of the left mesial temporal lobe and perisylvian region. This early finding
      evolved to volume loss and later progressive atrophy of the ipsilateral
      hemisphere when epilepsia partialis continua occurred. Being aware of those early
      MRI features in a patent with increasing frequency of focal motor seizures should
      suggest Rasmussen's syndrome. In addition, we found prominently increased
      myoinositol concentration in atrophic cortex which might reflect increased
      gliosis in the late period of the disease.

PMID- 10879712
TI  - Cervical chordoma with vertebral artery encasement mimicking neurofibroma: MRI
      findings.
AB  - A case of cervical chordoma in a 36-year-old white man with hypoesthesia in the
      neck and right shoulder, neck pain, and restricted neck mobility is presented.
      Plain radiographs of the cervical spine showed radiolucency of the body of C2 on
      the right side and enlargement of the right intervertebral foramen at C2-C3
      level. Tumor encasement of the vertebral artery was demonstrated by MR imaging
      and confirmed by conventional arteriography. This proved to be particularly
      important for preoperative assessment.

PMID- 10879713
TI  - MR analysis of nasopharyngeal carcinoma: correlation of the pattern of tumor
      extent at the primary site with the distribution of metastasized cervical lymph
      nodes. Preliminary results.
AB  - The purpose of this study was to correlate the pattern of tumor extent of
      nasopharyngeal carcinoma at the primary site on magnetic resonance (MR) imaging
      with the distribution of cervical lymph node metastasis. MR images of 32 patients
      with biopsy-proven nasopharyngeal carcinoma were reviewed and classified into
      five patterns of tumor extent in correlation with the distribution of cervical
      lymphadenopathy. The assessment of cervical lymph node metastasis was done on the
      basis of the computed tomography (CT) findings. The tumor volume was also
      correlated with the occurrence of contralateral lymphadenopathy. Of the 32
      patients, five (16%) presented as type 1, tumor limited to the nasopharyngeal
      mucosa; 12 (38%) as type 2a, tumor which had invaded either lateral side but did
      not extend over the roof of nasopharynx; three (9%) as type 2b, tumor which had
      invaded bilaterally across the midline but did not extend over the roof of
      nasopharynx; three (9%) as type 2c, tumor which had invaded mainly the skull base
      but did not cross the midline; and nine (28%) as type 3, tumor which had extended
      anteriorly to the nasal cavity without invasion. Twenty-five patients (78%)
      demonstrated cervical lymphadenopathy. Patients with type 1, type 2b and type 3
      spread had frequent bilateral cervical lymphadenopathy; those with type 2a had
      only ipsilateral lymphadenopathy. There was statistical significance (P < 0.005)
      regarding the existence of contralateral lymphadenopathy with midline tumors as
      well as the absence of contralateral cervical lymphadenopathy with non-midline
      tumors. This study therefore suggests that the distribution of metastasized lymph
      nodes depends on the pattern of tumor extent at the primary site.

PMID- 10879714
TI  - Aberrant cervical thymus in an infant: an unusual cause of stridor.
AB  - We report an 8-month-old infant presenting with stridor caused by a nonpalpable
      neck mass discovered at imaging and surgery. The diagnosis of aberrant thymic
      tissue was confirmed at histopathology. The authors reviewed the literature and
      discuss the embryology, imaging findings and differential diagnosis of this rare
      disorder.

PMID- 10879715
TI  - Diagnostic potential of virtual bronchoscopy: advantages in comparison with axial
      CT slices, MPR and mIP?
AB  - The aim of this study was to evaluate the diagnostic potential of virtual
      endoscopy (VE) and to compare it with axial CT slices, multiplanar
      reconstructions (MPR), minimal intensity projections (mIP), and bronchoscopy in
      patients diagnosed with bronchogenic carcinoma. Thirty patients underwent a
      spiral CT. Axial CT images were transferred to an Onyx workstation (Silicon
      Graphics, Sun Microsystems, Mountain View, Calif.) for performing virtual
      endoscopy. Accuracy for this procedure was tested by three radiologists on a
      monitor in comparison with axial CT slices, MPR, mIP, and bronchoscopy concerning
      the localization and degree of stenoses. Endoluminal tumors were identified by
      virtual bronchoscopy with no statistically significant difference of localization
      or grading of stenosis in comparison with bronchoscopy, axial CT slices, MPR and
      mIP. Axial CT slices, MPR, and mIP showed poorer results with over- or
      underestimation of stenoses compared with VE and bronchoscopy. Passing of
      stenoses was only possible with VE in 5 patients. Virtual endoscopy is a non
      invasive method for identification of endoluminal tumors and is comparable to
      real bronchoscopy.

PMID- 10879716
TI  - MR arthrography of the shoulder: comparison of low-field (0.2 T) vs high-field
      (1.5 T) imaging.
AB  - The objective of this study was to compare the image quality, sensitivity,
      specificity, and diagnostic accuracy of an open low-field MR system (0.2 T) with
      a standard high-field MR system (1.5 T) after arthrography of the shoulder.
      Thirty-eight patients either with suspected chronic instability (n = 12) or
      rotator cuff abnormalities (n = 26) were examined. Intra-articular injection of
      diluted Gd-DTPA was followed in randomized order either first by imaging on an
      open 0.2-T system or on a 1.5-T system. The image material was evaluated
      independently by two radiologists in a blinded fashion with respect to overall
      image quality and the detection of rotator cuff as well as capsular and labral
      abnormalities. Surgical correlation was available in 27 (71%) of 38 patients. For
      both systems, sensitivity and specificity for rotator cuff tears were 100% each,
      and for labrum pathologies, these values were 100 and 93%, respectively. The
      agreement for detection of labral pathologies between low-field and high-field
      examinations was good (kappa = 0.69, kappa = 0.61). For the detection of full
      thickness tears of the rotator cuff, the agreement between the low-field and high
      field MR examinations was very good and significant (kappa = 0.94, kappa = 1, p <
      0.001). Overall image quality was rated good in 17 (45%) and fair in 21 (55%) of
      38 cases on the 0.2-T MR system, and good in 32 (84%) and fair in 6 (16%) of 38
      cases on the 1.5-T system. Motion artifacts were considered low in 24 (63%) and
      moderate in 14 (37%) of 38 cases for the 0.2-T system and low in 34 (89%) and
      moderate in 4 (11%) for 1.5-T system. Based on our results, low-field MR compares
      favorably to high-field MR in the detection of major abnormalities of the
      glenohumeral joint, at least when MR arthrography is used. Disadvantages are the
      duration of the examination and thus the risk of reduced image quality caused by
      motion artifacts.

PMID- 10879717
TI  - Imaging of compressive vertebral haemangiomas.
AB  - Compressive vertebral haemangiomas (VHs) are rare. Correct preoperative diagnosis
      is useful both for operative planning (since compressive VHs are extremely
      vascular lesions) and to allow preoperative embolisation. Numerous radiological
      signs for VHs have been described, but compressive VHs frequently have atypical
      features. In particular, magnetic resonance features are not well established. We
      present imaging features in three cases of compressive VH and review the imaging
      findings in an additional 106 previously published cases. Findings were typical
      in 52 of 80 plain film (65%), 33 of 41 computed tomography (80%) and 13 of 25
      magnetic resonance examinations (52%). The prevalence of previously described
      imaging features is reported. Awareness of the range of magnetic resonance
      features is important since this is frequently the initial investigation in
      patients presenting with symptoms of neural compression. Since computed
      tomography is typical in 80% of cases, this is a useful confirmatory test if
      magnetic resonance features are suspicious but not diagnostic of compressive VH.

PMID- 10879718
TI  - The crowned dens syndrome: a rare form of calcium pyrophosphate deposition
      disease.
AB  - The crowned dens syndrome has been termed as acute neck pain ascribed to CPPD
      deposits associated with a tomographic appearance of calcification surrounding
      the odontoid process. This rare entity resulting in cervical cord compression is
      generally seen in older female patients. We present a 26-year-old woman with
      cervical cord compression due to massive calcification in the periodontoid area
      and discuss the X-ray and CT findings of the disease.

PMID- 10879719
TI  - A comparison of the time required by radiologists for the preparation of clinico
      radiological meetings when film and PACS are used.
AB  - The hypothesis was that when a hospital-wide Picture Archive and Communications
      System (PACS) is used, preparation for clinico-radiological meetings is faster,
      and more images are available, than when a conventional film system is used. This
      paper reports a study which compared the preparation time by radiologists when
      film was used with the time for the same activity when a hospital-wide PACS was
      used at Hammersmith Hospital for the preparation of the respirator medicine and
      hepato-biliary meeting. It was found that when PACS was used the time per patient
      to prepare for the respiratory medicine session was reduced by 11.1 min and that
      similarly, 16 min per patient was saved in the preparation of the hepato-biliary
      sessions. The number of images which were unavailable for the session was reduced
      when PACS was in operation, but this reduction was not shown to be statistically
      significant. The introduction of PACS at Hammersmith Hospital has significantly
      reduced the time spent by radiologists in preparing for the two clinico
      radiological sessions studied and, if this is extended to the other numerous
      sessions held each week, contributes to a considerable saving of staff time
      within the radiology department.

PMID- 10879720
TI  - CT-guided intervention using a patient laser marker system.
AB  - To prove the usefulness of a simple laser marker system (LMS) in target
      definition as well as examination procedure for CT-guided interventions, 130
      cases of diagnostic biopsies and lumbal sympathectomies were compared. In 75
      cases LMS and in 55 cases a simple crossgrid was used. Taking advantage of the
      LMS, the parameters of intervention (cutaneous location, length, and angle) can
      be planned, exactly demonstrated, and it is possible to check the needle position
      during the whole procedure. Thus, the number of necessary control scans decreased
      to 30%, and corrections of needle location were reduced to approximately 30%.
      Moreover, the average target deviation of the needle decreased below 5 mm in 50%
      of cases, and the duration of interventional procedure was reduced considerably.
      It can be concluded that LMSs are recommended in CT-guided interventions for
      quality assurance, dose reduction, and improvement of handling. It will be
      especially advantageous in cases of small target volume, oblique needle path, and
      tilted gantry.

PMID- 10879721
TI  - Vetting requests for body computed tomography.
AB  - The aim of this study was to assess the process and outcome of hospitalised
      patients (inpatients) for whom whole-body CT was requested but not performed. For
      6 months the reasons why CT was not performed were recorded, together with
      relevant discussions with clinicians. Subsequent referrals for alternative
      investigations were noted. The eventual outcome of the patients was monitored via
      the patients' records. Eighty-three (8%) of 1001 inpatient requests were
      identified for which body CT was not performed after an electronically generated
      request. Fifty-five requests were not accepted by the radiology department during
      the vetting process for a variety of reasons (often more than one): criteria used
      for rejection often overlapped and included referrals outside national guidelines
      (n = 20), better alternative investigations (n = 29), time constraints (n = 19),
      over-zealous requests (n = 17) and clinicians' erroneous interpretation of
      preceding imaging investigations (n = 9). Sixteen CT exams were cancelled by a
      clinician. An additional 12 exams were not performed for miscellaneous non
      medical reasons. In no case could a patient's death be ascribed to CT not being
      performed. Most (981 of 1001, 98%) CT requests comply with current guidelines,
      disproving a perception that many radiological referrals are inappropriate. In
      our health care system radiologists have to turn down some appropriate CT
      referrals due to a lack of CT capacity. Although lack of CT contributed to delay
      in diagnosis, no patient died as a direct result of not having CT.

PMID- 10879722
TI  - Migration pathways of hypodermically injected technetium-99m in dogs.
AB  - Hypodermic injection of technetium-99m (99mTc-pertechnetate) at points of low
      electrical resistance give rise to rapid, longitudinal, and progressive diffusion
      of the radioactive tracer. We assessed the effect of cutaneous incisions that did
      not intersect the migration trajectory of 99mTc-pertechnetate and the re
      establishment of pathways after the suture of incisions that intersected the
      migration trajectory. Linear and rapid migration of 99mTc-pertechnetate was not
      altered or prevented by incisions that did not intersect the migration pathway.
      Different patterns of 99mTc-pertechnetate spread were found when incisions
      intersected the radioactive pathways until restoration of the normal migration
      pathway observed in undamaged skin occurred. In all experiments in which
      migration of 99mTc-pertechnetate was observed, lavage of surgical wounds was
      followed by disappearance of the 99mTc-pertechnetate migration observed around
      the suture. Linear migration of the tracer was not observed when the incision was
      left uncovered, filled with petroleum jelly, or with a solid silicone sheet, but
      it was seen when non-sutured incisions were filled with transonic or silicone gel
      or covered with a solid silicone sheet parallel to the cutaneous plane. These
      data show that after a cutaneous incision that intersected the diffusion
      trajectory of the radioactive tracer, linear migration of 99mTc-pertechnetate
      hypodermically injected at points of low electrical resistance was restored
      before healing of the cutaneous incision and was independent of incisions made on
      the skin not overlying the radioactive pathway. A mechanism similar to that of
      capillary electrophoresis is suggested to explain the hypodermic diffusion of
      inert particles through specific and constant linear pathways.

PMID- 10879723
TI  - Uptake of 111In-pentetreotide and 99mTc-labeled autologous granulocytes in
      Kimura's disease.
AB  - Uptake of 111In-pentetreotide (OctreoScan) and 99mTc-labeled autologous
      granulocytes by the lesions of a 37-year-old female from Thailand with Kimura's
      disease is described. This is a benign chronic inflammatory condition that is
      endemic in Asians. It is characterized by adenopathy and subcutaneous nodules
      mostly affecting the head and neck area or the salivary glands. Although these
      examinations have previously not been described in Kimura's disease, uptake of
      the radiopharmaceuticals in the lesions can be expected from their histological
      appearance. With increasing medical, social and economic interactions with Asia,
      it is important to recognize this cause of adenopathy, including its appearance
      at various nuclear medicine examinations.

PMID- 10879724
TI  - Benign intramammary and axillary lesions mimicking malignancy.

PMID- 10879725
TI  - Bilateral breast involvement in acute myelogenous leukemia.

PMID- 10879726
TI  - Embolization of giant aneurysm and pseudoaneurysm of the splenic artery.

PMID- 10879727
TI  - Real-time bolus-triggering technique in helical CT: efficacy in identifying
      inflow vein thrombosis.

PMID- 10879728
TI  - Preoperative magnetic resonance cholangiography of a severe case with Caroli's
      disease complicated by hepatolithiasis.

PMID- 10879729
TI  - Radiology 2000: new_generation@rad.century_2.1K.

PMID- 10879730
TI  - Simultaneous quantitation of topoisomerase II alpha and beta isoform mRNAs in
      lung tumor cells and normal and malignant lung tissue.
AB  - Certain drugs used in the treatment of lung cancer and other human malignancies
      are cytotoxic because of their ability to interact with the two isoforms of
      topoisomerase II (topo II), topo IIalpha and topo IIbeta. As part of an effort to
      evaluate the contribution of topo II alterations to drug sensitivity and
      resistance in lung cancer, we have developed a semi-quantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) assay to measure levels of topo
      II alpha and beta mRNAs simultaneously using a single pair of primers with
      sequences common to both isoforms. The PCR products derived from the topo II
      alpha and beta mRNAs are both 446 bp but have different electrophoretic
      mobilities in a nondenaturing polyacrylamide gel, allowing sensitive, rapid
      quantitation when the products are radiolabeled with [35S]-dATP. Using this RT
      PCR method, poly(A+) RNA from 13 non-small cell lung cancer (NSCLC) cell lines
      was analyzed. The results obtained indicated that the cell lines express a wide
      range of topo II alpha mRNA levels (12-fold) and topo IIbeta mRNA levels (5.5
      fold). Tumor and normal lung tissues from 25 patients with NSCLC were also
      examined. In the tumor samples, the levels of the topo II alpha and beta mRNAs
      were similar. However, mean topo IIalpha mRNA levels in the tumors were
      approximately 7-fold higher than those of the paired normal lung tissues. In
      contrast, topo IIbeta mRNA levels were similar in both tumor and normal lung.
      Topo II alpha and beta mRNA levels were both significantly lower in the squamous
      cell tumors than in the adenocarcinoma samples. Topo IIbeta mRNA levels in the
      squamous cell tumors were also significantly lower than those in paired normal
      lung tissue. The RT-PCR method described is reliable and convenient, and for the
      first time, makes the rapid simultaneous direct comparison of topo IIalpha and
      topo IIbeta mRNA levels feasible in large numbers of clinical samples.

PMID- 10879731
TI  - Proliferation-associated expression of the MEN1 gene as revealed by in situ
      hybridization: possible role of the menin as a negative regulator of cell
      proliferation under DNA damage.
AB  - The gene responsible for multiple endocrine neoplasia type 1 (MEN1) has recently
      been identified. Wide expression of the MEN1 gene in endocrine and non-endocrine
      organs examined by northern blotting has been reported, but the detailed cellular
      distribution of the MEN1 transcript in each tissue has not yet been examined in
      any species. In this report, expression of the MEN1 gene in adult human tissues
      was studied by in situ hybridization. The MEN1 transcript was widely observed in
      all tissues examined, and an enhanced expression in relation to cell
      proliferation was seen in some organs. Cell cycle arrest at the G1-S border
      reduced the MEN1 mRNA level to less than 50% of that in exponentially growing
      asynchronous cells. The expression increased as cells entered into S phase,
      indicating cell cycle-associated transcriptional regulation of the MEN1 gene.
      Increase or decrease of the amount of menin did not affect proliferation of CHO
      cells under normal conditions. However, when cells were exposed to the DNA-cross
      linking agent, diepoxybutane, overexpression of wild-type menin inhibited DNA
      synthesis. This effect was not observed when cells were exposed to ultraviolet
      light. These results suggest that menin may negatively regulate cell cycle under
      certain DNA damage.

PMID- 10879732
TI  - Analysis of SYT-SSX fusion transcripts and bcl-2 expression and phosphorylation
      status in synovial sarcoma.
AB  - Synovial sarcomas (SS) are characterized by a chromosomal translocation
      t(X;18)(p11.2;q11.2) which usually fuses the SYT gene from chromosome 18 to SSX1
      or SSX2 genes on chromosome X. Also, a variant SYT-SSX4 fusion gene has recently
      been shown in a single SS case. In addition to these cytogenetic changes, bcl-2
      expression, as assessed by immunohistochemistry, has been reported to be an
      almost general constitutive alteration of SS. In the present work, we analyze a
      series of 36 SS surgical samples (from 34 patients) by RT-PCR for the presence of
      the SYT-SSX1 or the SYT-SSX2 fusion transcript. The analysis was extended to SYT
      SSX4 on SYT-SSX1-negative and SYT-SSX2-negative cases only. Our results showed a
      significant correlation between the SYT-SSX2 fusion and the monophasic SS
      histologic subtype. SYT-SSX1 fusion transcripts were present in both monophasic
      and biphasic tumors. The SYT-SSX4 fusion type was detected in a single monophasic
      SS. In the same series of SS cases, we also confirmed and extended the previously
      reported constitutive expression of bcl-2 protein, by using both
      immunohistochemical and western blot analysis. Moreover, we demonstrated that the
      BCL-2 gene is not rearranged or amplified at genomic level, indicating that the
      high levels of bcl-2 expression observed in SS might result from transcriptional
      activation of the gene and/or protein stabilization. Finally, we show that bcl-2
      is not phosphorylated in tumors from patients who had been preoperatively treated
      with radio/chemotherapy, in tumors from untreated patients, or in an SS cell line
      (CME-1) after in vitro treatment with cytotoxic concentrations of DNA-damaging
      agents or taxanes. These data indicate that SS cells are unable to activate an
      apoptosis pathway involving bcl-2 phosphorylation/inactivation and may provide a
      possible explanation for the limited effectiveness of conventional
      pharmacological treatments of this tumor type.

PMID- 10879733
TI  - Acute humoral xenograft rejection: destruction of the microvascular capillary
      endothelium in pig-to-nonhuman primate renal grafts.
AB  - The major cause of xenograft loss beyond hyperacute rejection is a form of
      injury, traditionally termed delayed xenograft rejection (DXR), whose
      pathogenesis is unknown. Here we analyze the immunologic and morphologic features
      of DXR that develops in pig kidney xenografts transplanted into nonhuman
      primates. Kidneys from miniature swine were transplanted into cynomolgus monkeys
      (n = 14) or baboons (n = 11) that received regimens aimed to induce mixed
      chimerism and tolerance. No kidney was rejected hyperacutely. Morphologic and
      immunohistochemical studies were performed on serial biopsies, and an effort was
      made to quantify the pathologic features seen. The early phase of DXR (Days 0-12)
      was characterized by focal deposition of IgM, IgG, C3, and scanty neutrophil and
      macrophage infiltrates. The first abnormality recognized was glomerular and
      peritubular capillary endothelial cell death as defined by in situ DNA nick-end
      labeling (TUNEL). Damaged endothelial cells underwent apoptosis and, later, frank
      necrosis. The progressive phase developed around Day 6 and was characterized by
      progressive deposition of IgM, IgG, C3, and prominent infiltration of cytotoxic T
      cells and macrophages, with a small number of NK cells. Thrombotic
      microangiopathy developed in the glomeruli and peritubular capillaries with
      TUNEL+ endothelial cells, platelet aggregation, and destruction of the capillary
      network. Only rare damaged arterial endothelial cells and tubular epithelial
      cells were observed, with rare endothelialitis and tubulitis. In the advanced
      phase of DXR, interstitial hemorrhage and infarction occurred. During the
      development of DXR, the number of TUNEL+ cells increased, and this correlated
      with progressive deposition of antibody. The degree of platelet aggregation
      correlated with the number of TUNEL+ damaged endothelial cells. We conclude that
      peritubular and glomerular capillary endothelia are the primary targets of renal
      DXR rather than tubular epithelial cells or arterial endothelium and that the
      earliest detectable change is endothelial cell death. DXR was characterized by
      progressive destruction of the microvasculature (glomeruli and peritubular
      capillaries) and formation of fibrin-platelet thrombi. Both cytotoxic cells and
      antibodies potentially mediate the endothelial damage in DXR; however, in this
      model, DXR is largely humorally mediated and is better termed "acute humoral
      xenograft rejection."

PMID- 10879734
TI  - Comparative genomic hybridization analysis of myoepithelial carcinoma of the
      breast.
AB  - Although there seems to be a common stem cell for the two epithelial cell types
      in the breast, the vast majority of breast cancers exhibit a luminal phenotype.
      Pure myoepithelial carcinomas are rare. We report our findings of genetic
      alterations in these tumors. We have analyzed 10 cases of pure myoepithelial cell
      carcinomas using laser capture microdissection and comparative genomic
      hybridization. The mean number of changes was 2.1 (range 0-4), compared with a
      mean of 8.6 (range 3.6-13.8) in unselected ductal carcinomas. Common alterations
      included loss at 16q (3/10 cases), 17p (3/10), 11q (2/10), and 16p (2/10),
      regions also commonly deleted in ductal carcinomas. The single case in which both
      pure myoepithelial carcinoma and invasive ductal carcinoma was present showed 2
      alterations in the myoepithelial tumor (losses at 17p and 17q), whereas the
      invasive ductal component showed 15 alterations (5 gains and 9 losses), including
      loss at 17p. The sharing of 17p loss in myoepithelial and ductal carcinoma is
      consistent with a common stem cell model in the breast. The relatively few
      genetic alterations in otherwise aggressive neoplasms suggests that myoepithelial
      tumors may be a good model for the delineation of genes important in breast
      tumorigenesis.

PMID- 10879735
TI  - Vascular apoptosis and involution in gliomas precede neovascularization: a novel
      concept for glioma growth and angiogenesis.
AB  - Vascular changes in gliomas were analyzed by implanting fluorescent-labeled
      glioma 261 cells in the brains of 28 mice. Seven animals were killed each week
      for 4 weeks. We investigated the expression of angiopoietin-2 (Ang-2) by in situ
      hybridization and compared it with the distribution of apoptotic cells identified
      by DNA strand breaks (using the terminal deoxynucleotidyl transferase-mediated
      biotinylated deoxyuridine triphosphate nick end labeling [TUNEL] method) and
      transmission electron microscopy (TEM). As early as 1 week after implantation,
      tumor cells accumulated around vessels, which expressed Ang-2 and were TUNEL
      negative. TEM showed tumor cells adjacent to the vascular cells "lifting up" the
      normal astrocytic feet processes away from the endothelial cells and disrupting
      normal pericytic cuffing. After 2 weeks the number of perivascular glioma cells
      had increased. No increase in the number of blood vessels was detected at this
      time. Vascular cells remained positive for Ang-2 and rare ones were TUNEL
      positive. TEM showed closely packed proliferating perivascular tumor cells. After
      3 weeks, there was vascular involution with scant zones of tumor necrosis. Ang-2
      was still detected in vascular cells, but now numerous vascular cells were TUNEL
      positive. In addition, TEM showed apoptotic vascular cells. After 4 weeks, there
      were extensive areas of tumor necrosis with pseudopalisading and adjacent
      angiogenesis. Ang-2 was detected in vascular cells at the edge of the tumors in
      the invaded brain and in vessels surrounded by tumor cells. At both 3 and 4
      weeks, most of the TUNEL-positive tumor cells lacked morphological features
      characteristic of apoptosis and displayed features consistent with necrotic cell
      death as determined by TEM. Only rare tumor cells appeared truly apoptotic. In
      contrast, the TUNEL-positive endothelial cells and pericytes were round and
      shrunken, with condensed nuclear chromatin by TEM, suggesting that vascular cells
      were undergoing an apoptotic cell death. These results suggest that vascular cell
      apoptosis and involution preceded tumor necrosis and that angiogenesis is a later
      event in tumor progression in experimental gliomas. Moreover, Ang-2 is detected
      prior to the onset of apoptosis in vascular cells and could be linked to vascular
      involution.

PMID- 10879736
TI  - Assessment of genotype and molecular evolution of hepatitis C virus in formalin
      fixed paraffin-embedded liver tissue from patients with chronic hepatitis C virus
      infection.
AB  - Drawbacks of hepatitis C virus (HCV) RNA detection in paraffin-embedded liver
      tissue have satisfactorily been solved by RT-PCR amplification of the 5'non
      coding region (5'NCR). However, detection of this highly conserved region does
      not provide information on epidemiological or pathogenetic aspects of HCV
      infection. This study explores whether other functionally important genetic
      regions of HCV, such as the hypervariable region 1 (HVR-1) and the interferon
      sensitivity-determining region (ISDR), can be retrieved from paraffin-embedded
      liver specimens by RT-PCR, and whether the amplified material is suitable for
      further molecular analyses. RT-PCR amplification of 5'NCR, HVR-1, and ISDR was
      assessed in RNA extracted from 50 formalin-fixed, paraffin-embedded liver
      specimens, including 23 needle liver biopsies (11 from patients with non-A, non-B
      chronic hepatitis diagnosed between 1971 and 1985, 8 from subjects with normal
      liver histology and 4 from sequential biopsies from a patient with HCV recurrence
      after liver transplantation), and 27 liver explants from patients undergoing
      transplantation between 1988 and 1996 (16 with HCV-related cirrhosis and 11 with
      other disorders). The 5'NCR was successfully amplified in 8 of 11 (73%) non-A,
      non-B chronic hepatitis biopsies and in all of the specimens from patients with
      serological documentation of HCV infection. There were no false-positive results.
      HCV genotype was identified by RFLP analysis of the 5'NCR in the 13 cases
      analyzed. HVR-1 and ISDR were amplified in 24 of 28 (86%) samples, which were
      positive for the 5'NCR. Efficient amplification was inversely related to the time
      of storage. The evolutionary changes of HVR-1 and ISDR were successfully analyzed
      by direct sequencing of amplificates from the explanted liver and from the
      sequential liver biopsies in a patient with HCV infection recurrence after
      transplantation. These observations indicate that paraffin-embedded liver tissue,
      even when stored for more than 20 years, is appropriate for advanced studies on
      the molecular biology of HCV.

PMID- 10879737
TI  - Cystic fibrosis F508del patients have apically localized CFTR in a reduced number
      of airway cells.
AB  - Present state of knowledge, mostly based on heterologous expression studies,
      indicates that the cystic fibrosis transmembrane conductance regulator (CFTR)
      protein bearing the F508del mutation is misprocessed and mislocalized in the
      cytoplasm, unable to reach the cell surface. Recently, however, it was described
      that protein levels and localization are similar between F508del and wild-type
      CFTR in airway and intestinal tissues, but not in the sweat glands. In this
      study, we used immunocytochemistry with three different anti-CFTR antibodies to
      investigate endogenous CFTR expression and localization in nasal epithelial cells
      from F508del homozygous patients, F508del carriers, and non-CF individuals. On
      average, 300 cells were observed per individual. No significant differences were
      observed for cell type distributions among CF, carrier, and non-CF samples;
      epithelial cells made up approximately 80% to 95% of all cells present. CFTR was
      detected mostly in the apical region (AR) of the tall columnar epithelial (TCE)
      cells, ciliated or nonciliated. By confocal microscopy analysis, we show that the
      CFTR apical region-staining does not overlap with either anti-calnexin
      (endoplasmic reticulum), anti-p58 (Golgi), or anti-tubulin (cilia) stainings. The
      median from results with three antibodies indicate that the apical localization
      of CFTR happens in 22% of TCE cells from F508del homozygous patients with CF (n =
      12), in 42% of cells from F508del carriers (n = 20), and in 56% of cells from
      healthy individuals (n = 12). Statistical analysis indicates that differences are
      significant among all groups studied and for the three antibodies (p < 0.05).
      These results confirm the presence of CFTR in the apical region of airway cells
      from F508del homozygous patients; however, they also reveal that the number of
      cells in which this occurs is significantly lower than in F508del carriers and
      much lower than in healthy individuals. These findings may have an impact on the
      design of novel pharmacological strategies aimed at circumventing the CF defect
      caused by the F508del mutation.

PMID- 10879739
TI  - T-cell-dependent fibrosis in the mdx dystrophic mouse.
AB  - In Duchenne muscular dystrophy patients, the pathological hallmark of the
      disease, namely, the chronic accumulation of sclerotic scar tissue in the
      interstitial space of skeletal muscle is attributed to manifestation of secondary
      pathological processes. Such anomalous generation of matrix protein is thought to
      be driven by the continuous degeneration and regeneration of muscle both in
      Duchenne Muscular Dystrophy and in the mdx mouse homolog. We examined mdx and the
      control strain C57bl/10 mice over a range of ages with respect to the amounts of
      collagen present in muscles and other organs, finding that the mdx have
      significantly higher collagen content at later time points in their kidney and
      lung as well as their muscles. Surprisingly, when we bred the mdx mice on the
      nu/nu background, the time course of fibrogenesis was modified depending on the
      tissue and the collagen content was significantly different in age-matched mice.
      Transplantation of normal thymic tissue into the mdx-nu/nu mice replenished their
      T-cells and concomitantly altered the collagen content in their tissues to levels
      comparable with those in immunocompetent mdx mice. This suggests that T-cells
      play a role in the onset of the fibrotic events that undermines the ability of
      dystrophic muscle to regenerate.

PMID- 10879738
TI  - Phenotypic characteristics and cyclin-dependent kinase inhibitors repression in
      hyperplastic epithelial pathology in idiopathic focal segmental
      glomerulosclerosis.
AB  - Hyperplastic glomerular epithelial lesion is an important determinant of the
      progression of idiopathic focal segmental glomerulosclerosis (FGS). The
      proliferation and differentiation of glomerular epithelial cells and parietal
      epithelial cells (PECs) are regulated differently by cyclin and cyclin-dependent
      kinase inhibitors (CKIs) during nephrogenesis. To access the cellular mechanism
      underlying epithelial hyperplasia in the development of FGS, the present study
      applied immunohistochemistry to 21 cases of FGS to demonstrate expression of cell
      cycle molecules and phenotypic characterization in proliferative epithelial
      lesions in FGS. The materials included segmental sclerosis (18.1%), which was
      divided into monolayer epithelial lesions (64.6%) and cellular lesions (35.4%).
      All of the cellular lesions expressed cytokeratin, frequently with Ki-67 (82.4%)
      and less frequently with cyclin A (17.7%), but were invariably negative for
      podocyte markers (PHM-5 and synaptopodin) and CKIs (p27kip1 and p57kip2).
      Podocytes in nonsclerotic tuft in the same glomeruli with cellular lesions
      strongly expressed CKIs and podocyte markers. Moreover, electron microscopy
      showed that some large proliferating cells with prominent nucleoli have a broad
      cell base attached to Bowman's capsule. These cells have cilia and a junctional
      complex with neighboring hyperplastic cells, some of which directly cover the
      glomerular basement membrane. This suggests that cellular lesions are of PEC
      origin. Monolayer epithelial lesions also exclusively exhibited a PEC phenotype
      with reciprocal expression of podocyte markers and cytokeratin. In addition, CKIs
      are weakly expressed in monolayer epithelial lesions, suggesting a re-entry of
      cell-cycle quiescent. In conclusion, proliferation of PEC, sustained by
      repression of CKIs in nature and simultaneous activation of cyclin A, is the
      actual molecular background to the cellular lesions in FGS. Cellular lesions may
      result in monolayer epithelial lesions that retain the PEC phenotype and enter a
      common pathway to glomerulosclerosis.

PMID- 10879740
TI  - Expression of cyclin-dependent kinase 6 (cdk6) and frequent loss of CD44 in nasal
      nasopharyngeal NK/T-cell lymphomas: comparison with CD56-negative peripheral T
      cell lymphomas.
AB  - Lymphomas involving the nasal and nasopharyngeal region mainly include CD56
      positive natural killer (NK)/T-cell lymphomas, CD56-negative peripheral T-cell
      lymphomas (PTL), and B-cell lymphomas. Among these, the CD56-positive lymphoma,
      presumably of an NK/T-cell nature, is frequently seen in Asian, Mexican, and
      South American patients. NK cells are proposed to be closer developmentally to T
      cells than to other lymphoid cells, because bipotential common progenitor cells
      of NK/T-cell lineage have been isolated. In this study, we collected 47 cases of
      nasal lymphoma and investigated the phenotypic difference between NK/T-cell
      lymphoma and PTL by examining the pattern of the developmentally differentially
      expressed molecules cdk6 (cyclin-dependent kinase 6), CD44, CD117, and by
      examining the rearrangement of the T-cell receptor gene (TcR-GR). cdk6, an
      essential regulator of the cell cycle in G1 progression, was over-expressed in a
      subset of cortical thymocytes, but absent in mature thymocytes. In contrast,
      CD44, a glycosylated adhesion molecule, was absent in cortical thymocytes, but
      present in mature thymocytes and peripheral activated T cells. We found both over
      expression of nuclear cdk6 (n-cdk6) and frequent absence of CD44 in nasal CD56
      positive NK/T-cell lymphomas, in contrast to most nasal CD56-negative PTL, which
      were CD44-immunoreactive with weak or no expression of n-cdk6. Almost all tested
      cases of NK/T-cell lymphoma displayed a germ-line configuration of TcR, without
      evidence of gene rearrangement. Thus, there seems to be a useful distinction
      between the classical NK/T type of nasal lymphoma (CD56+/n-cdk6+/CD44-/TcR-GR-)
      and PTL (CD56-/n-cdk6-/CD44+/TcR-GR+) involving the nasal region. The presence of
      Epstein-Barr virus does not seem to be a good marker for distinguishing between
      NK/T lymphoma and PTL involving the nasal region.

PMID- 10879741
TI  - Correction of defective host response to Mycobacterium bovis BCG infection in TNF
      deficient mice by bone marrow transplantation.
AB  - Tumour necrosis factor-alpha (TNF) plays a central role in the recruitment and
      activation of mononuclear cells in mycobacterial infection. In the absence of
      type 1 TNF receptor, Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection
      of mice is not contained, leading to fatal disease. Because type 1 TNF receptor
      binds both TNF and lymphotoxin-a, we used TNF-deficient mice to determine the
      specific role of TNF in the host resistance to BCG infection. The bacterial
      burden of the lungs of TNF-deficient mice was substantially increased and the
      mice succumbed to pneumonia between 8 and 12 weeks with a defective granuloma
      response. Atypical granulomas developed by 4 weeks expressing low levels of MHC
      class II, intracellular adhesion molecule (ICAM-1), CD11b and CD11c. Macrophages
      showed little signs of activation and had low levels of acid phosphatase activity
      and inducible nitric oxide synthase (INOS) expression. Despite the defective
      cellular recruitment, the chemokines, monocyte chemoattractant protein-1 (MCP-1)
      and macrophage inflammatory protein-1 (MIP-1alpha), were increased in broncho
      alveolar lavage fluid of TNF-deficient mice. The defective host response was
      corrected by the transplantation of normal bone marrow cells into irradiated TNF
      deficient mice. These results demonstrate that TNF derived from hemopoietic cells
      rather than from mesenchymal origin are essential for a normal host response to
      BCG infection. Furthermore, TNF dependent expression of adhesion molecules may be
      essential for the recruitment of mononuclear cells for the formation of
      bactericidal BCG granulomas.

PMID- 10879742
TI  - Differences in caveolae dynamics in vascular smooth muscle cells of different
      phenotypes.
AB  - Vascular smooth muscle cells shift between two major differentiated states with
      distinct morphological and functional properties, a contractile and a synthetic
      phenotype. Here, primary cultures were used to study caveolae expression and
      dynamics in these cells. The results demonstrate that caveolae are more numerous
      and more actively interact with intracellular organelles in contractile than in
      synthetic cells. Immunohistochemistry showed that caveolin-1 was mainly localized
      to caveolae in contractile cells and partly shifted to Golgi-associated vesicles
      in synthetic cells, whereas caveolin-2 chiefly appeared in cytoplasmic vesicles
      in both cases. Cholera toxin B subunit, a ligand of GM1 ganglioside, was
      internalized via caveolae and carried to endosomes and Golgi-associated vesicles.
      In contractile cells, it later moved into Golgi and endoplasmic reticulum (ER)
      cisternae and thus had access to the entire endocytic and exocytic pathways. In
      contrast, in synthetic cells, the tracer was restricted to the endocytic pathway.
      Filipin staining similarly disclosed that cholesterol was more widely distributed
      in contractile than in synthetic cells, with strong labeling of both caveolae and
      adjacent ER portions. Although no direct continuity between caveolae and ER was
      detected, it is suggested that cholesterol and other molecules may be
      translocated between these compartments. The observed differences in caveolae
      expression and dynamics are likely to be significant for the differences in
      proliferative capacity and cholesterol transport between contractile and
      synthetic smooth muscle cells.

PMID- 10879743
TI  - Identification of genetic markers for prostatic cancer progression.
AB  - Despite the high incidence of prostate cancer, only limited data are available on
      genes or chromosomes specifically involved in its initiation and progression. We
      have applied comparative genomic hybridization to routinely processed, paraffin
      embedded, tissues at different times in prostatic tumor progression to screen the
      tumor genome for gains and losses. Our panel included specimens derived from 56
      different patients: 23 patients with primary, prostate-confined carcinomas; 18
      patients with regional lymph node metastases; and 15 patients with distant
      metastases. Chromosome arms that most frequently showed losses, included 13q
      (55%), 8p (48%), 6q (43%), 5q (32%), 16q (25%), 18q (20%), 2q (18%), 4q (18%),
      10q (18%), and Y (16%). Gains were often seen of chromosome arms 8q (36%), 17q
      (23%), Xq (23%), 7q (21%), 3q (18%), 9q (18%), 1q (16%), Xp (16%). Furthermore,
      specific high-level amplifications, eg, of 1q21, 1q25, and Xq12 to q13, were
      found in metastatic cancers. A significant accumulation of genetic changes in
      distant metastases was observed, eg, loss of 10q (p = 0.03) and gain of 7q (p =
      0.03) sequences. In addition, investigation of a potential biomarker identified
      in previous studies by our group, ie, extra copies of #7 and/or #8, revealed a
      high prevalence of 7pq and/or 8q gain in the distant metastases (p = 0.02).
      Importantly, gains were observed more frequently in tumors derived from
      progressors after radical prostatectomy, than in nonprogressors (mean time of
      follow-up, 74 months). Specifically, gain of chromosome 7pq and/or 8q sequences
      appeared an accurate discriminator between the progressors and nonprogressors.
      Multivariate analysis showed a significant correlation between progressive
      disease and the number of chromosomes with gains. This correlation also held true
      when stage (p = 0.007) or grade (p = 0.002) were taken into account. Likewise,
      this applied for gain of chromosome 7pq and/or 8q sequences (p = 0.03 and p =
      0.005 for stage or grade, respectively). Additionally, an increase in the number
      of chromosomes with gains per case was related to a decrease in biochemical
      progression-free survival (Ptrend <0.001). More specifically, the gain of 7pq
      and/or 8q sequences markedly reduced the biochemical progression-free survival (p
      < 0.001). In conclusion, this study has, firstly, documented the spectrum of
      chromosomal alterations in subsequent stages of prostate cancer, a number of
      which had not been described previously. It allowed us to identify chromosomal
      regions related to advanced tumor stage, ie, loss of 10q24 and gain of 7q11.2
      and/or 7q31 sequences. Secondly, gain of 7pq and/or 8q was identified as a
      potential genetic discriminator between progressors and nonprogressors after
      radical surgery.

PMID- 10879744
TI  - E-selectin expression and stimulation by inflammatory mediators are
      developmentally regulated during embryogenesis.
AB  - Leukocyte recruitment during inflammation is specified, in part, by the spatial
      distribution and temporal regulation of endothelial adhesion molecules. In this
      study we investigated the developmental onset of E-selectin and intercellular
      adhesion molecule-1 (ICAM-1) basal expression and inducibility by inflammatory
      mediators as indices of lineage-restricted endothelial adhesion molecule
      expression. We studied both murine embryos and embryoid bodies (EB), derived from
      differentiated embryonic stem cells, to examine a broad range of endothelial
      ontogeny. Our results reveal that E-selectin and ICAM-1 are differentially
      regulated during development and that three stages define the ontogeny of the E
      selectin-inducible response. The earliest endothelial lineage cells in Day 4 and
      Day 5 EB did not express E-selectin in the basal state or after stimulation. A
      second stage, observed between embryonic Day 9.5 (E9.5) and E11.5 to E12.5 in
      cultured embryo cells and transiently at Day 6 of EB differentiation, was
      characterized by basal expression that was not stimulated by inflammatory
      mediators. A third stage was characterized by both basal and inducible expression
      of E-selectin and was observed beginning at E12.5 to E13.5 in cultured embryo
      cells and at Day 7 in EB. In contrast ICAM-1 was stimulated at all of the
      embryonic stages examined and before the onset of E-selectin inducibility in both
      embryos and EB. E-selectin expression in embryos was also stimulated by
      introducing endotoxin into the embryonic, but not the maternal, peritoneum. This
      suggests that embryos are protected from inflammatory insults present in the
      maternal circulation. The developmentally regulated acquisition of E-selectin
      inducibility during embryogenesis likely involves changes in signal transduction
      cascades, transcription factors, and/or chromatin accessibility that specify
      inducible expression within the endothelial lineage and further restrict
      inducibility to particular endothelial subpopulations.

PMID- 10879746
TI  - Pathogenesis of placental site trophoblastic tumor may require the presence of a
      paternally derived X chromosome.
AB  - Placental site trophoblastic tumor (PSTT) is a neoplastic proliferation of
      intermediate trophoblasts that invades the myometrium at the placental site after
      a pregnancy. Less than 100 cases have been reported. Information of the sex
      assignment of the antecedent gestation is available in 21 cases: 18 of these were
      female. To explore this interesting phenomenon, we have determined the sex
      chromosome composition of the tumor tissue preserved in paraffin blocks for five
      new cases of this condition. The last documented gestational event included a
      normal vaginal delivery of female infants in three cases, normal vaginal delivery
      of an infant of unknown sex in one case and a molar gestation in one case. Using
      the X-linked human androgen receptor (AR) gene as a polymorphic marker, we showed
      that in all five cases the tumor had a likely XX chromosomal composition; and in
      four cases it was possible to determine that one of the X chromosomes was of
      paternal origin. In one case, the paternal X chromosome showed no polymorphism to
      either maternal X chromosomes. In addition, sensitive semi-nested PCR failed to
      show a human Y chromosome element in any of the five cases of PSTT. Overall, of
      21 cases from the literature and 5 cases of ours, 89% (23 of 26) showed an XX
      genomic composition in PSTT, either by history or genetic analysis. These results
      suggest that most PSTT were derived from the antecedent female conceptus and were
      likely to have possessed a functional paternal X chromosome. Methylation status
      analysis at the AR locus was performed in the three PSTT in which the paternal X
      chromosome was identifiable. In two cases, the paternal AR locus was
      hypomethylated while the corresponding maternal locus was hypermethylated. The
      methylation status of other loci was not investigated. Collectively, sex
      chromosome analysis of five cases of PSTT with literature support suggests a
      unique genetic basis for the development of PSTT that involves the paternal X
      chromosome. Although largely speculative, an active paternal X chromosome may be
      of importance in the pathogenesis of PSTT.

PMID- 10879745
TI  - Over-expression of TSC-22 (TGF-beta stimulated clone-22) markedly enhances 5
      fluorouracil-induced apoptosis in a human salivary gland cancer cell line.
AB  - We have recently isolated TSC-22 (transforming growth factor-beta-stimulated
      clone-22) cDNA as an anticancer, drug-inducible (with vesnarinone) gene in a
      human salivary gland cancer cell line, TYS. We have also reported that TSC-22
      negatively regulates the growth of TYS cells and that down-regulation of TSC-22
      in TYS cells plays a major role in salivary gland tumorigenesis (Nakashiro et al,
      1998). In this study, we transfected TYS cells with an expression vector encoding
      the TSC-22-GFP (green fluorescent protein) fusion protein, and we established TSC
      22-GFP-expressing TYS cell clones. Next, we examined (a) the subcellular
      localization of the fusion protein, (b) the sensitivity of the transfectants to
      several anticancer drugs (5-fluorouracil, cis-diaminedichloroplatinum,
      peplomycin), and (c) induction of apoptotic cell death in the transfectants by 5
      fluorouracil treatment. The TSC-22-GFP fusion protein was clearly localized to
      the cytoplasm, but not to the nucleus. Over-expression of the TSC-22-GFP fusion
      protein did not affect cell growth, but significantly increased the sensitivity
      of the cells to the anticancer drugs (p < 0.01; one-way ANOVA). Furthermore, over
      expression of the TSC-22-GFP fusion protein markedly enhanced 5-fluorouracil
      induced apoptosis. These findings suggest that over-expression of TSC-22-GFP
      protein in TYS cells enhances the chemosensitivity of the cells via induction of
      apoptosis.

PMID- 10879747
TI  - Regulation of aminopeptidase A in human brain tumor vasculature: evidence for a
      role of transforming growth factor-beta.
AB  - Angiotensin peptides are potent vasoconstrictors, cell growth factors, and
      neuromodulators in normal and pathological situations. To assess the potential
      role of the angiotensins in brain tumor-associated vessels, the expression of the
      enzymes of the angiotensin cascade were evaluated in these tumors. The production
      of these bioactive peptides is dependent on the activities of exopeptidases,
      including several aminopeptidases and carboxypeptidases, producing angiotensin
      (Ang) I, II, III, IV and Ang 1-7. Human cerebral parenchymal and glioblastoma
      cells expressed renin, and tumor vasculature, but not glioblastoma cells,
      expressed angiotensin-converting enzyme. High aminopeptidase A (APA) activity,
      but no aminopeptidase N/B activity, was observed in human brain tumor
      vasculature, suggesting a predominant production of Ang III. Grafting of rat
      glioma cells in rat brains yielded tumors with high APA and low aminopeptidase
      N/B activities in tumor vessels, confirming human results. Tumor growth and APA
      activity in tumor vessels were not affected by chronic angiotensin-converting
      enzyme inhibition. The brain-derived EC219 endothelial cells expressed high APA
      activity, which was not involved in endothelial cell proliferation, but was down
      regulated by exposure of cells to transforming growth factor-beta (TGF beta) or
      to TGF beta-secreting tumor cells, suggesting a role for this peptide in the
      control of APA activity in cerebral vasculature. Thus, APA is a potential marker
      of chronic dysfunction, involving loss of TGF beta function, of the metabolic
      blood-brain barrier, but not of neovascularization.

PMID- 10879748
TI  - Identification of necrotic tissue by phase-contrast microscopy at an early stage
      of acute myocardial infarction.

PMID- 10879749
TI  - Simultaneous quantitation of several mRNA species by calibrated reverse
      transcription polymerase chain reaction and capillary electrophoresis: analysis
      of the epidermal growth factor receptor and its activating ligands EGF, TGF
      alpha, and HB-EGF in rat liver.

PMID- 10879750
TI  - One-step method for endothelial cell isolation from large human blood vessels
      using fibrin glue.

PMID- 10879751
TI  - Methylprednisolone for acute spinal cord injury: an inappropriate standard of
      care.
AB  - OBJECT: Since publication in 1990, results from the National Acute Spinal Cord
      Injury Study II (NASCIS II) trial have changed the way patients suffering an
      acute spinal cord injury (SCI) are treated. More recently, recommendations from
      NASCIS III are being adopted by institutions around the world. The purpose of
      this paper is to reevaluate carefully the results and conclusions of these
      studies to determine the role they should play in influencing decisions about
      care of the acutely spinal cord-injured patient. METHODS: Published results from
      NASCIS II and III were reviewed in the context of the original study design,
      including primary outcomes compared with post-hoc comparisons. Data were
      retroconverted from tabular form back to raw form to allow direct inspection of
      changes in treatment groups. These findings were further analyzed with respect to
      justification of practice standards. Although well-designed and well-executed,
      both NASCIS II and III failed to demonstrate improvement in primary outcome
      measures as a result of the administration of methylprednisolone. Post-hoc
      comparisons, although interesting, did not provide compelling data to establish a
      new standard of care in the treatment of patients with acute SCI. CONCLUSIONS:
      The use of methylprednisolone administration in the treatment of acute SCI is not
      proven as a standard of care, nor can it be considered a recommended treatment.
      Evidence of the drug's efficacy and impact is weak and may only represent random
      events. In the strictest sense, 24-hour administration of methylprednisolone must
      still be considered experimental for use in clinical SCI. Forty-eight-hour
      therapy is not recommended. These conclusions are important to consider in the
      design of future trials and in the medicolegal arena.

PMID- 10879752
TI  - Use of structural allografts in spinal osteomyelitis: a review of 47 cases.
AB  - OBJECT: The use of structural allografts in spinal osteomyelitis remains
      controversial because of the perceived risk of persistent infection related to a
      devitalized graft and spinal hardware. The authors have identified 47 patients
      over the last 3.5 years who underwent a surgical decompression and stabilization
      procedure in which fresh-frozen allografts were used after aggressive removal of
      infected and devitalized tissue. The patients subsequently underwent 6 weeks of
      postoperative antibiotic therapy (12 months for those with tuberculosis [TB]).
      METHODS: Follow-up data included results of serial clinical examinations,
      radiography, laboratory analysis (erythrocyte sedimentation rate and white blood
      cell count), and clinical outcome questionnaires. Of the original 47 patients (14
      women and 33 men, aged 14-83 years), 39 were available for follow up. The average
      follow-up period at the time this article was submitted was 17 +/- 9 months
      (median 14 months, range 6-45 months). In the majority of cases (57%), a
      Staphylococcus species was the infectious organism. Predisposing risk factors
      included intravenous drug abuse (IVDA), previous surgery, diabetes, TB, and
      concurrent infections. During the follow-up period only two patients suffered
      recurrent infection at a contiguous level; both had a history of IVDA and one
      also had a chronic excoriating skin condition. No other recurrent infections have
      been identified, and no patient has required reoperation for persistent infection
      or allograft/hardware failure. CONCLUSIONS: It is the authors' opinion that the
      use of structural allografts in combination with aggressive tissue debridement
      and adjuvant antibiotic therapy provide a safe and effective therapy in cases of
      spinal osteomyelitis requiring surgery.

PMID- 10879753
TI  - Acute cervical cord injury without fracture or dislocation of the spinal column.
AB  - OBJECT: It is known that the spinal cord can sustain traumatic injury without
      associated injury of the spinal column in some conditions, such as a flexible
      spinal column or preexisting narrowed spinal canal. The purpose of this study was
      to characterize the clinical features and to understand the mechanisms in cases
      of acute cervical cord injury in which fracture or dislocation of the cervical
      spine has not occurred. METHODS: Eighty-nine patients who sustained an acute
      cervical cord injury were treated in our hospitals between 1990 and 1998. In 42
      patients (47%) no bone injuries of the cervical spine were demonstrated, and this
      group was retrospectively analyzed. There were 35 men and seven women, aged 19 to
      81 years (mean 58.9 years). The initial neurological examination indicated
      complete injury in five patients, whereas incomplete injury was demonstrated in
      37. In the majority of the patients (90%) the authors found degenerative changes
      of the cervical spine such as spondylosis (22 cases) or ossification of the
      posterior longitudinal ligament (16 cases). The mean sagittal diameter of the
      cervical spinal canal, as measured on computerized tomography scans, was
      significantly narrower than that obtained in the control patients. Magnetic
      resonance (MR) imaging revealed spinal cord compression in 93% and paravertebral
      soft-tissue injuries in 58% of the patients. CONCLUSIONS: Degenerative changes of
      the cervical spine and developmental narrowing of the spinal canal are important
      preexisting factors. In the acute stage MR imaging is useful to understand the
      level and mechanisms of spinal cord injury. The fact that a significant number of
      the patients were found to have spinal cord compression despite the absence of
      bone injuries of the spinal column indicates that future investigations into
      surgical treatment of this type of injury are necessary.

PMID- 10879754
TI  - Transpedicular approaches to cervical uncovertebral osteophytes causing
      radiculopathy.
AB  - OBJECT: The anterolateral and posterior transpedicular foraminotomies were
      developed to enhance the treatment of cervical spondylotic radiculopathy
      secondary to uncovertebral osteophytes. These novel surgical approaches may be
      advantageous because they allow direct decompression of the nerve root while
      preserving normal movement and stability of the motion segment. The use of the
      pedicle to obtain access to compressive uncovertebral osteophytes, without
      causing damage to the motion segment, has not been previously reported. METHODS:
      The authors present the early outcome data obtained in 27 patients who underwent
      an anterolateral or posterior foraminotomy. Eighty-eight percent of patients who
      underwent anterolateral foraminotomy and 94% of those who underwent a posterior
      transpedicular procedure experienced complete or significant relief of
      brachialgia. Postoperatively none of the patients were symptomatically or
      neurologically worse. CONCLUSIONS: The transpedicular approach is an effective
      and potentially improved method of treating symptomatic cervical uncovertebral
      osteophytes compared with techniques previously described.

PMID- 10879755
TI  - Spectrum of occipitoatlantoaxial injury in young children.
AB  - OBJECT: Injuries of the occipitoatlantoaxial (Oc-C2) region are the predominant
      form of cervical injury in children younger than 10 years of age. Magnetic
      resonance (MR) imaging can be used to visualize directly the traumatic
      ligamentous and soft-tissue abnormalities of the Oc-C2 region. A retrospective
      review was undertaken to examine the spectrum of pediatric Oc-C2 injuries seen on
      MR imaging, their correlation with plain x-ray film and computerized tomography
      findings, and their clinical course. METHODS: Seventy-one consecutive children
      younger than 10 years of age underwent cervical MR imaging for evaluation of
      traumatic injury. Magnetic resonance imaging was used to document abnormalities
      in 23 children; 20 of these injuries involved the Oc-C2 region. Abnormalities in
      the Oc-C2 region included disruptions of the musculature, apical ligament,
      atlantooccipital joint(s), tectorial membrane, and spinal cord. A spectrum of
      injury with progressive involvement of these structures was seen, ranging from
      isolated muscular injury to the multiple soft-tissue and ligamentous disruptions
      with craniocervical dislocation. Involvement of the tectorial membrane was the
      critical threshold in the transition from stable to unstable injury. Analysis of
      plain x-ray films revealed that a novel interspinous C1-2:C2-3 ratio criteria of
      greater than or equal to 2.5 was predictive of tectorial membrane abnormalities
      on MR imaging, with 87% sensitivity and 100% specificity. In patients with
      tectorial membrane abnormalities who underwent immobilization alone, interim
      platybasia was demonstrated on follow-up MR images. Conclusions. A progressive
      spectrum of distinct Oc-C2 injuries can occur in young children; the tectorial
      membrane is a critical stabilizing ligamentous structure in the Oc-C2 complex;
      and tectorial membrane abnormalities may be identified by a C1-2:C2-3 ratio of
      greater than or equal to 2.5.

PMID- 10879756
TI  - New method for intraoperative determination of proper screw insertion or screw
      malposition.
AB  - OBJECT: Inadequate imaging techniques may lead to misjudgment of screw
      positioning when applying transpedicular instrumentation; this can create
      potential risks of major vessel and nerve damage. In this article the authors
      present a new method to determine screw malpositioning intraoperatively. METHODS:
      The authors retrospectively evaluated pre- and postoperative plain radiographs of
      97 spinal segments in which screws had been placed in 41 patients suffering from
      thoracolumbar injury who had previously undergone transpedicular screw fixation.
      They developed a new mathematical equation with which they determine the distance
      ratios of two screw tips in the same segment by comparing the distance between
      the pedicles on preoperative radiographs with those on postoperative radiographs.
      Subsequently, the results are compared with postoperative computerized tomography
      findings to determine which screws are in the correct position and which are
      penetrating the medial or lateral cortex of the pedicle. It was found that the
      ratio range of correctly placed screw tips was 46 +/- 10% (mean +/- standard
      deviation) in the thoracic region and 60 +/- 9% in the lumbar region (ranges 43
      50% and 57-63%, respectively, 95% confidence intervals). Higher ratios (higher
      percentages) than these values indicated extreme closeness of screw tips and
      therefore medial malpositioning. Lower ratios (lower percentages) indicated
      lateral malpositioning. CONCLUSIONS: This proposed method may provide
      intraoperative determination of correct screw positioning or malpositioning. This
      method allows surgeons to replace the malpositioned screw, and, consequently,
      early resolution of neurovascular injuries is made possible. Additionally,
      repositioning of the screw correctly will avoid rigidity failure of the fixation
      device.

PMID- 10879757
TI  - Complications of posterior lumbar interbody fusion when using a titanium threaded
      cage device.
AB  - OBJECT: The authors reviewed their series of patients to quantify clinical and
      radiographic complications in those who underwent a posterior lumbar interbody
      fusion (PLIF) procedure in which a threaded interbody cage (TIC) was implanted.
      METHODS: Sixty-seven patients underwent a posterior lumbar interbody fusion
      procedure in which a TIC was used. The authors excluded patients who underwent
      procedures in which other instrumentation was used or a nondorsal approach was
      performed. Fifteen percent of the cases (10 patients) were complicated by
      laceration of the dura. In three cases, bilateral implantation could not be
      performed. The average blood loss was 670 ml for all cases, and blood transfusion
      was required in 25% of the cases (17 patients). The rate of minor wound
      complication was 4.5% (three patients). One patient died. The average period of
      hospitalization was 4.25 days. Twenty-eight patients (42%) experienced
      significant low-back pain 3 months postoperatively, and in 10 (15%) of these
      cases it persisted beyond 1 year. In 10 patients postoperative radiculopathy was
      demonstrated, and magnetic resonance imaging revealed epidural fibrosis in six
      patients, arachnoiditis in one, and a recurrent disc herniation in one. One
      patient incurred a permanent motor deficit with sexual dysfunction.
      Pseudarthrosis was suggested radiographically with evidence of motion on lateral
      flexion-extension radiographs (10 cases), lucencies around the implants (seven
      cases), and posterior migration of the cage (two cases). Additional procedures
      (in 14 patients) consisted primarily of transverse process fusion with pedicle
      screw and plate augmentation for persistent back pain and radiographically
      demonstrated signs of spinal instability. In two patients with radiculopathy,
      migration of the TIC required that it be removed. Graft material that extruded
      from one implant necessitated its removal. In one patient scarectomy was
      performed. CONCLUSIONS: Our high incidence of TIC-related complications in PLIF
      is inconsistent with that reported in previous studies.

PMID- 10879758
TI  - Surgical evaluation and management of lumbar synovial cysts: the Mayo Clinic
      experience.
AB  - OBJECT: The authors report a retrospective analysis of 194 patients surgically
      treated at their institutions for symptomatic lumbar synovial cysts from January
      1974 to January 1996. METHODS: Patient characteristics including age, sex,
      symptoms, signs, and preoperative neuroimaging studies were reviewed. Surgical
      procedures, complications, results, and pathological findings were correlated
      with preoperative assessment. One hundred ninety-four patients were surgically
      treated for symptomatic lumbar synovial cysts. Eighty percent were diagnosed and
      treated between 1987 and 1996. There were 100 men and 94 women with an average
      age of 66 years (range 28-94 years). The most common symptoms were painful
      radiculopathy (85%) and neurogenic single or multiroot claudication (44%).
      However, sensory loss (43%) and motor weakness (27%) were also presenting
      symptoms. Eleven percent of patients had undergone previous lumbar surgery prior
      to being referred to the Mayo Clinic. Preoperative neurological examination
      demonstrated motor weakness (40%), sensory loss (45%), reflex changes (57%), and
      variants of cauda equina syndrome (13%). In 19% of patients, normal neurological
      status was demonstrated. There was equal left/right-sided laterality, and eight
      patients presented with bilateral synovial cysts. The most commonly affected
      level was L4-5 (64%). All patients underwent laminectomy and resection of the
      cyst. Concomitant fusion was performed in 18 patients in whom clinical evidence
      of instability had been observed. However, subsequent fusion was required in only
      four patients who developed symptomatic spondylolisthesis. Surgery-related
      complications included cerebrospinal fluid leak (three patients), discitis (one
      patient), epidural hematoma (one patient), seroma (one patient), and deep vein
      thrombosis (one patient). One patient died 3 days after surgery of cardiac
      dysrhythmia. Follow-up data obtained for at least 6 months postoperatively were
      available in 147 patients. Of these, 134 (91%) reported good relief of their pain
      and 82% experienced improvement in their motor deficits. CONCLUSIONS: Lumbar
      synovial cysts are a more common cause of lumbar radicular pain than previously
      thought. Surgical removal of the cyst is a safe and effective treatment for
      symptomatic relief in patients with lumbar synovial cysts. A concomitant fusion
      procedure may be performed in select cases. In this study, only a few patients
      developed symptomatic spinal instability requiring a second operation.

PMID- 10879759
TI  - Dynamic examination of the lumbar spine by using vertical, open magnetic
      resonance imaging.
AB  - OBJECT: The aim of this study was to determine the relationship of different
      structures of the lower lumbar spine during interventional movement examination.
      METHODS: Clinically healthy volunteers and patients suffering from degenerative
      disorders of the lumbar spine underwent vertical, open magnetic resonance (MR)
      imaging (0.5 tesla). Three functional patterns of lumbar spine motion were
      identified in 50 healthy volunteers (average age 25 years). The authors
      identified characteristic angles of the facet joints, as measured in the frontal
      plane. In 50 patients with degenerative disorders of the lumbar spine (41 with
      disc herniation, five with osteogenic spinal stenosis, and four with degenerative
      spondylolisthesis) the range of rotation was increased in the relevant spinal
      segments. Signs of neural compression were increased under motion. CONCLUSIONS:
      Dynamic examination in which vertical, open MR imaging is used demonstrated that
      the extent of neural compression as well as the increasing range of rotation are
      important signs of segmental instability.

PMID- 10879760
TI  - Spinal intramedullary cavernoma: clinical presentation and surgical outcome.
AB  - OBJECT: Improved neuroimaging techniques have led to an increase in the reported
      cases of intramedullary cavernomas. The purpose of this study was to define the
      spectrum of presenting signs and symptoms in patients with spinal intramedullary
      cavernomas and to analyze the role of surgery as a treatment for these lesions.
      METHODS: The authors reviewed the charts of 16 patients who underwent surgery for
      spinal intramedullary cavernomas. All patients underwent preoperative magnetic
      resonance imaging studies. Cavernomas represented 14 (5.0%) of 280 intramedullary
      lesions found in adults and two (1.1%) of 181 intramedullary lesions found in
      pediatric cases. A posterior laminectomy and surgical resection of the
      malformation were performed in all 16 patients. CONCLUSIONS: Magnetic resonance
      imaging is virtually diagnostic for spinal cavernoma lesions. Patients with
      spinal intramedullary cavernomas presented with either an acute onset of
      neurological compromise or a slowly progressive neurological decline. Acute
      neurological decline occurs secondary to hemorrhage within the spinal cord.
      Chronic progressive myelopathy occurs due to microhemorrhages and the resulting
      gliotic reaction to hemorrhagic products. There is no evidence that cavernomas
      increase in size. The rate of rebleeding is unknown, but spinal cavernomas appear
      to be clinically more aggressive than cranial cavernomas, probably because the
      spinal cord is less tolerant of mass lesions. Complete surgical removal of the
      cavernoma was possible in 15 of 16 of the authors' cases.

PMID- 10879761
TI  - Effects of cervical spinal cord stimulation on cerebral blood flow in the rat.
AB  - OBJECT: Spinal cord stimulation (SCS) is frequently used for the treatment of
      chronic pain. Although the mechanisms by which SCS alleviates pain are unclear,
      they are believed to involve changes within the dorsal horn of the spinal cord.
      Spinal cord stimulation has also been found to cause significant vasodilation in
      the peripheral vasculature. The mechanisms underlying this effect are thought to
      involve sympathetic blockade. A rostral vasodilatory effect has also been
      described, but changes in cerebral blood flow (CBF) have been poorly delineated.
      Using laser Doppler flowmetry (LDF), the authors examined the effects of cervical
      SCS on CBF in rats. METHODS: Cervical SCS was found to result in a significant
      increase in cortical LDF values (83 +/- 11% [mean +/- standard error of the
      mean]). The increase in cortical LDF values was not accompanied by a significant
      increase in systemic blood pressure. Stimulation of the upper cervical spinal
      cord was more effective in inducing LDF changes than was that of the lower
      cervical cord. Changes in SDS-induced LDF values were significantly attenuated
      after spinal cord transection at the cervicomedullary junction and by the
      administration of the sympathetic blocker hexamethonium. CONCLUSIONS: These
      results indicate that cervical SCS may induce cerebral vasodilation and that this
      effect may involve indirect effects on vasomotor centers in the brainstem as well
      as an alteration in sympathetic tone.

PMID- 10879762
TI  - Comparison of the effects of melatonin and methylprednisolone in experimental
      spinal cord injury.
AB  - OBJECT: Melatonin is a very effective antioxidant agent. This study was performed
      to investigate the effects of melatonin in experimental spinal cord injury (SCI).
      The authors also compared its effects with those of methylprednisolone, which
      also protects the spinal cord from secondary injury because of its antioxidant
      effect on membrane lipids. METHODS: Adult male albino rats were used for the
      study, and paraplegia was produced using a previously described weight-drop
      technique. Melatonin and methylprednisolone were given intraperitoneally by bolus
      injections of 100 mg/kg and 30 mg/kg, respectively, immediately after induction
      of trauma. The animals were killed, and 1-cm samples of injured spinal cord were
      obtained at 1, 24, and 48 hours postinjury. Lipid peroxidation was estimated by
      thiobarbituric acid test. Electron microscopic studies were performed to
      determine the effects of melatonin on neurons, axons, and subcellular organelles
      after experimental SCI. A grading system was used for quantitative evaluation.
      Following SCI, there was significant increase in lipid peroxidation. In melatonin
      and methylprednisolone-treated groups, lipid peroxidation was found to decrease
      to the baseline (preinjury) levels. There was a significant difference between
      trauma-alone and treatment groups, but no statistical difference was found
      between the melatonin- and methylprednisolone-treated groups. Electron
      microscopic findings showed that SCI produced by the weight-drop technique
      resulted in profound tissue damage. CONCLUSIONS: Both melatonin and
      methylprednisolone have been shown to protect neuron, axon, myelin, and
      intracellular organelles including mitochondrion and nucleus. However, this study
      provides quantitative evidence that this protection of neurons and subcellular
      organelles of spinal cord after secondary injury is much more obvious in
      melatonin-treated rats than those treated with methylprednisolone. In view of
      these data, melatonin has been shown to be very effective in protecting the
      injured spinal cord from secondary injury.

PMID- 10879763
TI  - Beneficial effects of modest systemic hypothermia on locomotor function and
      histopathological damage following contusion-induced spinal cord injury in rats.
AB  - OBJECT: Local spinal cord cooling (LSCC) is associated with beneficial effects
      when applied following ischemic or traumatic spinal cord injury (SCI). However,
      the clinical application of LSCC is associated with many technical difficulties
      such as the requirement of special cooling devices, emergency surgery, and
      complicated postoperative management. If hypothermia is to be considered for
      future application in the treatment of SCI, alternative approaches must be
      developed. The objectives of the present study were to evaluate 1) the
      relationship between systemic and epidural temperature after SCI; 2) the effects
      of modest systemic hypothermia on histopathological damage at 7 and 44 days post
      SCI; and 3) the effects of modest systemic hypothermia on locomotor outcome at 44
      days post-SCI. METHODS: A spinal cord contusion (12.5 mm at T-10) was produced in
      adult rats that had been randomly divided into two groups. Group 1 rats (seven in
      Experiment 1; 12 in Experiment 2) received hypothermic treatment (epidural
      temperature 32-33 degrees C) 30 minutes postinjury for 4 hours; Group 2 rats
      (nine in Experiment 1; eight in Experiment 2) received normothermic treatment
      (epidural temperature 37 degrees C) 30 minutes postinjury for 4 hours. Blood
      pressure, blood gas levels, and temperatures (epidural and rectal) were monitored
      throughout the 4-hour treatment period. Twice weekly assessment of locomotor
      function was performed over a 6-week survival period by using the Basso-Beattie
      Bresnahan locomotor rating scale. Seven (Experiment 1) and 44 (Experiment 2) days
      after injury, animals were killed, perfused, and their spinal cords were serially
      sectioned. The area of tissue damage was quantitatively analyzed from 16
      longitudinal sections selected from the central core of the spinal cord.
      CONCLUSIONS: The results showed that 1) modest changes in the epidural
      temperature of the spinal cord can be produced using systemic hypothermia; 2)
      modest systemic hypothermia (32-33 degrees C) significantly protects against
      locomotor deficits following traumatic SCI; and 3) modest systemic hypothermia
      (32-33 degrees C) reduces the area of tissue damage at both 7 and 44 days
      postinjury. Although additional research is needed to study the therapeutic
      window and long-term benefits of systemic hypothermia, these data support the
      possible use of modest systemic hypothermia in the treatment of acute SCI.

PMID- 10879765
TI  - Spinal stability with anterior or posterior ray threaded fusion cages.
AB  - OBJECT: The authors conducted a study to determine if the rigidity supplied to
      the spine by posterior placement of the Ray threaded fusion cage (TFC) is further
      enhanced by the placement of pedicle screws and, additionally, if bilateral
      anteriorly placed TFCs render the spine more rigid than a single anteriorly
      placed TFC. METHODS: Ten human cadaveric spinal specimens (L2-S1) were affixed
      within a testing frame. Loads of 1.5, 3, 4.5, and 6 Nm were applied to the spine
      in six degrees of freedom: flexion-extension, right and left lateral bending, and
      right and left axial rotation. Motion in an x, y, and z cartesian axis system was
      tracked using dual video cameras following light-emitting diodes attached to the
      spine and base plate. Load testing of the spines was performed in the intact
      mode, following which the spinal segments were randomized to receive anterior or
      posterior instrumentation. In five spine specimens we performed posterior
      discectomy, posterior lumbar interbody fusion (PLIF) with placement of femoral
      rings and pedicle screws, PLIF with bilateral TFCs, and bilateral TFCs with
      pedicle screws. Five other spines underwent anterior-approach discectomy,
      followed by implantation of a unilateral cage and bilateral cages. Load testing
      was performed after each step. CONCLUSION: Spines in which PLIF with pedicle
      screws and TFCs with pedicle screws were placed were more rigid than after
      discectomy in all directions of motion except flexion. Anterior discectomy
      provided significantly (p < or = 0.05) less stability in left and right axial
      rotation than the intact spines and following posterior discectomy. Following
      anterior implantation of bilateral TFCs, spines were significantly more rigid
      than after discectomy in all directions except extension.

PMID- 10879764
TI  - Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery
      after spinal cord injury in rats.
AB  - OBJECT: In Japan fasudil hydrochloride (HA1077), a protein kinase inhibitor, is
      widely administered to prevent vasospasm in patients after subarachnoid
      hemorrhage. The effects of fasudil on experimental spinal cord injury (SCI) were
      investigated and compared with those obtained using methylprednisolone. METHODS:
      Spinal cord contusion was induced in rats by applying an aneurysm clip
      extradurally to the spinal cord at T-3 for 1 minute. After injury three groups of
      rats were treated with intravenously administered saline (control),
      intraperitoneally administered fasudil (10 mg/kg), or intravenously administered
      methylprednisolone (four 30 mg/kg injections). Neurological recovery was
      evaluated periodically over 1 month by using a modified combined behavioral scale
      and histopathological examination. Leukocyte infiltration near the injury site
      was evaluated by measuring myeloperoxidase (MPO) activity at 24 hours. Spinal
      cord blood flow was measured at intervals up to 3 hours after injury by using
      laser Doppler flowmetry. In rats in the fasudil-treated group significant
      improvement in modified combined behavioral score was demonstrated at each time
      point, whereas in the methylprednisolone-treated rats no beneficial effects were
      shown. In the fasudil-treated group, reduction of traumatic spinal cord damage
      was evident histologically in the caudal portion of the injured areas, and tissue
      MPO activity in tissue samples was reduced. Spinal cord blood flow was not
      significantly different between fasudil-treated and control group rats.
      CONCLUSIONS: Fasudil hydrochloride showed promise of effectiveness in promoting
      neurological recovery after traumatic SCI. Possible mechanisms of this effect
      include protein kinase inhibition and decreased infiltration by neutrophils.

PMID- 10879766
TI  - A biomechanical comparison of the Rogers interspinous and the Lovely-Carl tension
      band wiring techniques for fixation of the cervical spine.
AB  - OBJECT: The authors conducted a biomechanical study in which they compared the
      uses of the Rogers interspinous and the Lovely-Carl tension band wiring
      techniques for internal fixation of the cervical spine. METHOD: An extensive
      biomechanical evaluation (stiffness in positive and negative rotations around the
      x, y, and z axes; range of motion in flexion-extension, bilateral axial rotation,
      and bilateral bending; and neutral zone in flexion-extension, bilateral axial
      rotation, and lateral bending to the right and to the left) was performed in two
      groups of intact calf cervical spines. After these initial tests, all specimens
      were subjected to a distractive flexion Stage 3 ligamentous lesion. Group 1
      specimens then underwent surgical fixation by the Rogers technique, and Group 2
      specimens underwent surgery by using the Lovely-Carl technique. After fixation,
      specimens were again submitted to the same biomechanical evaluation. The
      percentage increase or decrease between the pre- and postoperative parameters was
      calculated. These values were considered quantitative indicators of the efficacy
      of the techniques, and the efficacy of the two techniques was compared.
      CONCLUSIONS: Analysis of the findings demonstrated that in the spines treated
      with the Lovely-Carl technique less restriction of movement was produced without
      affecting stiffness, compared with those treated with the Rogers technique, thus
      making the Lovely-Carl technique clinically less useful.

PMID- 10879767
TI  - Validation and use of a finite element model of C-2 for determination of stress
      and fracture patterns of anterior odontoid loads.
AB  - OBJECT: The finite element (FE) method is a powerful tool for the analysis of
      stress patterns of anatomical structures. In this study a highly refined FE model
      of C-2 was created and validated. The model was then used to characterize stress
      patterns, predicted fracture patterns, and transitions between Type II and Type
      III odontoid fractures. METHODS: An anatomically accurate three-dimensional model
      of C-2 was created from computerized tomography data obtained from the Visible
      Human Project. The C-2 model was broken down into an FE mesh consisting of 32,815
      elements and 40,969 nodes. For validation, the FE model was constrained and
      loaded to simulate that used in previous biomechanical studies. The validated
      model was then loaded in an iterative fashion, varying the orientation of the
      load within the validated range. A matrix of stress plots was created for
      comparative analysis. Results of the validation testing closely correlated with
      those obtained in previous biomechanical testing. Pure extension loading produced
      a Type III stress pattern with maximum stress of 134 MPa. Loading at 45 degrees
      produced a Type II stress distribution with a maximum stress of 123 MPa. These
      stresses are within 3% and 11%, respectively, of the reported yield stress of
      cortical bone (138 MPa). In the second portion of the study, systematic variation
      in the orientation of the load vector revealed that higher stresses were
      associated with increased lateral angulation and increasing upward inclination of
      the load vectors. A transition from a Type III to Type II pattern occurred with
      lateral orientations greater than 15 degrees and with compressive loads of 45
      degrees. CONCLUSIONS: The validated C-2 FE model described in this study both
      qualitatively and quantitatively was able to simulate the behavior of the C-2
      vertebra in biomechanical testing. In this study the authors demonstrate the
      utility of the FE method when used in conjunction with traditional biomechanical
      testing.

PMID- 10879768
TI  - Microendoscopic posterior cervical foraminotomy: a cadaveric model and clinical
      application for cervical radiculopathy.
AB  - OBJECT: Cervical radiculopathy caused by either soft herniated disc material or
      foraminal stenosis is a common problem. Anterior and posterior surgical
      approaches are commonly used to decompress the nerve root. The authors undertook
      a study to establish the feasibility of performing a microendoscopic posterior
      approach for cervical foraminotomy in the clinical setting. METHODS: The authors
      performed an endoscopic posterior foraminotomy technique in which they used a
      rigid endoscope, in both a cadaver model and in three clinical cases, including
      one in which a multiple-level procedure was undertaken. Postoperatively, all
      patients returned to functional work status within 4 weeks. The mean length of
      hospitalization was 1.3 days. CONCLUSIONS: The advantages to this technique
      include improved intraoperative visualization, a smaller incision, and
      significantly less postoperative discomfort compared with a traditional keyhole
      approach.

PMID- 10879769
TI  - Congenital arthrogryposis associated with atlantoaxial subluxation and dysraphic
      abnormalities. Case report.
AB  - The authors report the case of a 27-year-old woman with an arthrogryposis
      multiplex congenita (AMC) associated with atlantoaxial subluxation. To the
      authors' knowledge, this is the first report of its kind. The authors review the
      literature with reference to dysraphic abnormalities associated with atlantoaxial
      subluxation and with AMC. The patient presented with severe tetraparesis
      following a minor traffic accident. She underwent a procedure in which transoral
      decompression and dorsal stabilization were performed and, postoperatively, made
      a good clinical outcome. The authors stress the need for diagnostic neuroimaging
      of the craniocervical junction in patients with AMC.

PMID- 10879770
TI  - Neurocutaneous vascular hamartomas mimicking Cobb syndrome. Case report.
AB  - The authors report the rare case of a patient with neurocutaneous vascular
      hamartomas mimicking Cobb syndrome. An 8-year-old boy was admitted to the
      authors' hospital with progressive urinary disturbance and upper back pain.
      Multiple skin nevi had been noted at the child's birth. Radiological examination
      revealed multiple cavernous angiomas in the spinal cord in the same metamere in
      which the skin nevi had been observed and also in the left cerebral hemisphere.
      His symptoms gradually improved without surgical intervention. Four years later
      he was readmitted because of a cerebral hemorrhage involving the left cerebral
      peduncle. Nonsurgical treatment was chosen because his symptoms promptly
      improved. To the best of the authors' knowledge, this is the first case of
      multiple cavernous angiomas in the brain and spinal cord associated with skin
      nevi. The authors discuss this clinical entity and the significance of the
      disease.

PMID- 10879771
TI  - Spinal intramedullary tuberculous lesion: medical management. Report of four
      cases.
AB  - The author describes the successful medical management of intramedullary
      tuberculous lesions in four patients who received treatment between 1994 and
      1997. The role of magnetic resonance imaging and the treatment protocol for
      intramedullary tuberculous lesions are also discussed.

PMID- 10879772
TI  - A viable residual spinal hydatid cyst cured with albendazole. Case report.
AB  - Spinal hydatid disease is a rare entity that frequently yields to severe, acute
      onset neurological deficits. Although the gold standard treatment is total
      surgical removal of the cysts without inducing any spillage, it may not be
      possible to perform this in patients with multiple and fragile cysts. In such
      cases, the neural structures should be adequately decompressed and albendazole
      should be administered promptly. The authors describe the case of a 13-year-old
      girl who was admitted with a history of back pain and acute-onset lower-extremity
      weakness. Magnetic resonance imaging scans demonstrated severe spinal cord
      compression caused by multiple cysts involving T-4 and the mediastinum. The
      patient underwent surgery, and the cysts were removed, except for one cyst that
      was hardly exposed. Following histopathological confirmation of spinal hydatid
      disease, she was treated with albendazole for 1 year. One year postoperatively,
      the residual cyst had gradually shrunk and had almost disappeared. Although a
      single case is not sufficiently promising, we believe that administration of
      albendazole is efficient to prevent recurrences in cases in which it is not
      possible to obtain total removal of the cysts without inducing spillage.

PMID- 10879773
TI  - Intramedullary spinal cord metastasis from gastric cancer. Case report.
AB  - A case of intramedullary spinal cord metastasis from gastric cancer is reported.
      A 51-year-old woman presented with hemicord syndrome that had progressed within 1
      month to tetraplegia. Despite total resection of the tumor, she died of
      disseminated intravascular coagulation and multiple organ failure. Examination of
      pathological findings demonstrated undifferentiated adenocarcinoma, and
      postoperative gastroendoscopic study revealed advanced gastric cancer. To the
      authors' knowledge this is the first case of intramedullary spinal cord
      metastasis from gastric cancer. The clinical characteristics of the disease are
      discussed.

PMID- 10879774
TI  - Capillary hemangioma of the spinal cord. Report of four cases.
AB  - The authors describe the clinicopathological features of four cases of capillary
      hemangioma of the spinal cord. All occurred in adult patients. The presenting
      symptoms were similar to those of more common intramedullary tumors.
      Radiologically, they resemble other vascular spinal cord tumors. All patients
      underwent surgery, and the outcomes varied. Histologically, the lesions resembled
      capillary hemangioma of skin or of soft tissue that is composed of lobules of
      small capillaries with associated feeding vessels, all enveloped by a delicate
      fibrous capsule. Capillary hemangiomas of the central and peripheral nervous
      system are extremely rare. Although examples of these lesions have been described
      as occurring in the dura mater and in peripheral nerve, including spinal nerve
      roots, none has occurred within the spinal cord. Knowledge of their existence may
      help practitioners to avoid misdiagnosis of tumor and resultant overtreatment of
      these benign lesions.

PMID- 10879775
TI  - Cervical epidural pseudotumor and multifocal fibrosclerosis. Case report and
      review of the literature.
AB  - The authors present the case of a 45-year-old man suffering from progressive
      quadriplegia due to an expansive C3-T2 epidural mass. Neuropathological
      examination demonstrated pseudotumor tissue. The patient had had an orbital
      pseudotumor 5 years before admission, and other systemic manifestations of an
      idiopathic inflammatory disease were discovered. This case is extremely rare.
      Nine cases of multifocal fibrosclerosis with central nervous system involvement
      are described in the literature. To the authors' knowledge, this is the first
      description of a cervical epidural pseudotumor. Modern imaging has made the
      diagnosis of such an entity possible, and it is important for the neurosurgeon to
      consider this syndrome because the combination of surgery and systemic medical
      therapy can ensure a long-term survival with good quality of life.

PMID- 10879776
TI  - Use of calcitonin for the treatment of an odontoid fracture. Case report.
AB  - The authors report on the efficacy of nonsurgical treatment of an older patient
      with a fractured odontoid process. The patient, an 85-year-old woman, had
      multiple medical problems that put her at an increased surgery-related risk.
      Therefore, an alternative approach was elected, including immobilization with a
      Philadelphia collar and the provision of calcitonin nasal spray. Bone union and
      clinical recovery were achieved within 8 weeks of initiating the nasal calcitonin
      therapy (12 weeks postinjury). Considering the patient's age, comorbidities, and
      the severity of the fracture, the recovery period was unusually short. The
      authors believe that calcitonin played a pivotal role in the healing process of
      the fractured odontoid bone. There is no question that the fusion in this patient
      could be unrelated to the medical therapy. This description of one patient, as
      well as the lack of a large randomized study, precludes any scientific
      conclusions. Nevertheless, the authors believe that the development of a
      successful fusion in this high-risk patient should be reported as an observation
      that merits confirmation and study. The authors also discuss the physiological
      effects of calcitonin and the research and clinical experience with this hormone
      in different conditions affecting bone.

PMID- 10879777
TI  - Minimally invasive retroperitoneal approach for lumbar corpectomy and anterior
      reconstruction. Technical note.
AB  - The anterior decompressive procedure in which spinal fusion is performed is
      considered an effective treatment for thoracolumbar fractures and tumors.
      However, it is also known to be associated with considerable surgery-related
      trauma. The purpose of this study was to show that lumbar corpectomy and anterior
      reconstruction can be performed via a minimally invasive retroperitoneal approach
      (MIRA) and therefore the surgical approach-related trauma can be reduced. The
      authors studied retrospectively the hospital records and radiological studies
      obtained in five patients (mean age 67.4 years, range 59-76 years) who underwent
      lumbar corpectomy and spinal fusion via an MIRA followed by posterior fixation.
      Four patients presented with osteoporotic compression fractures at L-2 and L-3,
      and one patient presented with metastatic disease in L-4 from prostate cancer.
      Neurological deficits due to cauda equina compression were demonstrated in all
      patients. The MIRA provided excellent exposure to facilitate complete
      decompression and anterior reconstruction in all patients, as verified on follow
      up radiographic studies. All patients improved clinically. A 1-year follow-up
      record is available for four patients and a 6-month follow-up record for the
      fifth patient; continuing clinical improvement has been observed in all.
      Radiography demonstrated anatomically correct reconstruction in all patients, as
      well as a solid fusion or a stable compound union in the four patients for whom 1
      year follow-up records were available. The MIRA allows the surgeon to perform
      anterior lumbar spine surgery via a less invasive approach. The efficacy and
      safety of this technique and its potential to reduce perioperative morbidity
      compared with conventional retroperitoneal lumbar spine surgery should be further
      investigated in a larger series.

PMID- 10879778
TI  - Evaluation of 11th rib extrapleural-retroperitoneal approach to the thoracolumbar
      junction. Technical note.
AB  - OBJECT: The 11th rib extrapleural-retroperitoneal approach offers an alternative
      means for access to the thoracolumbar junction. It provides excellent operative
      exposure without the need to transgress the diaphragm, resulting in less
      morbidity and reduced risk of pulmonary complications. This approach, however,
      has been dismissed by many surgeons offering the unsubstantiated criticism that
      it affords limited access. Thus far, only technical descriptions of the operative
      procedure are available in the literature, without documentation of the clinical
      outcomes of these patients. In the current study the authors describe the 11th
      rib extrapleural-retroperitoneal approach to the thoracolumbar junction, and they
      evaluate the associated early and late morbidity in these patients. METHODS: From
      September 1996 to August 1999, the authors collected prospective data of
      consecutive patients who underwent surgery for a variety of pathological
      conditions of the thoracolumbar junction via this approach. In 26 consecutive
      patients requiring an anterior spinal procedure, lesions located between T-10 and
      T-11 were studied and followed for a mean period of 17 months (range 1-36
      months). There were 13 men and 13 women whose mean age was 47 years (range 16-80
      years), with the following pathological entities: trauma (13 cases), neoplasm
      (six cases), infection (two cases), and deformity (five cases). There were no
      cases of neurological deterioration. There were no significant pulmonary
      complications, and only one patient required insertion of a postoperative chest
      tube. CONCLUSIONS: The 11th rib extrapleural-retroperitoneal approach was
      successfully used to treat patients with a variety of lesions in the
      thoracolumbar junction and was associated with little morbidity. The authors
      believe that previous criticism suggesting that this approach provides only
      limited access is unsubstantiated.

PMID- 10879779
TI  - Methylprednisolone and spinal cord injury.

PMID- 10879780
TI  - Correct intraoperative screw insertion.

PMID- 10879781
TI  - Nontraumatic acute spinal subdural hematoma.

PMID- 10879782
TI  - Nontraumatic acute spinal subdural hematoma.

PMID- 10879783
TI  - Hydatid disease.

PMID- 10879784
TI  - Changes in myopic refractive error with nine months' extended wear of hydrogel
      lenses with high and low oxygen permeability.

PMID- 10879785
TI  - Relapsing polychondritis.
AB  - BACKGROUND: Relapsing polychondritis (RPC) is a rare, chronic, and potentially
      fatal multisystemic inflammatory disorder targeting cartilaginous structures.
      This disorder is frequently associated with rheumatoid arthritis, systemic
      vasculitis, connective tissue diseases, and/or hematologic disorders. RPC
      afflicts patients with recurrent and often progressive episodes of inflammation
      with the potential for destruction of the affected structures. Tissues involved
      include the ears, joints, nose, larynx, trachea, eyes, heart valves, kidneys,and
      skin. Ocular manifestations commonly include episcleritis, scleritis,
      conjunctivitis, iridocyclitis, chorioretinitis, and proptosis. Lid edema, orbital
      inflammation, muscle palsies, and corneal melting may also occur. CASE REPORT: An
      83-year-old man previously diagnosed with RPC presented to our clinic with acute
      unilateral chemosis, conjunctivitis, lid edema, proptosis, and extraocular muscle
      restriction. After orbital cellulitis was ruled out, further evaluation revealed
      posterior scleritis with choroidal detachment OS. A course of oral indomethacin
      and topical antibiotic-steroid combination drops was implemented in the treatment
      of the ocular manifestations. The quick positive response to the anti
      inflammatory agents confirmed the diagnosis of ocular complications secondary to
      RPC. DISCUSSION: The presenting ocular signs and symptoms of RPC often resemble
      other commonly encountered ocular conditions. It is important for the eye care
      practitioner to be familiar with the ocular manifestations of RPC because the
      eyes are sometimes the initial site of involvement and may be a marker of
      severity. Early diagnosis and intervention may significantly improve the
      patient's outcome. This case report with literature review will hopefully bring
      to light features of this disease which will help the eye care practitioner in
      the diagnosis and management of this condition.

PMID- 10879786
TI  - The normal optic nerve head.
AB  - BACKGROUND: The normal optic nerve head varies from one person to another, and
      there is often intraindividual variation as well. Factors such as race and age
      play an important role in distinguishing what may be considered normal variations
      in optic nerve head appearance. METHODS: A literature search and review of the
      latest studies on the optic nerve head was conducted. RESULTS: Results of recent
      studies showed that variations in the average cup-to-disc ratio exist for
      different races, and with age there is a gradual loss of nerve fibers leading to
      an overall increase in the cup-to-disc ratio. There is also evidence that
      congenitally larger optic nerves have larger cup-to-disc ratios and more nerve
      fibers. Smaller optic nerves, in contrast, have smaller cup-to-disc ratios and
      fewer nerve fibers. These findings are presented along with sample photographs
      depicting the normal variations in optic nerve head appearance. CONCLUSION: Over
      the past 30 years, technology has allowed for changing views about what may be
      considered normal in reference to the optic nerve head. This information is
      valuable to the eye care practitioner in helping to make appropriate patient care
      management decisions.

PMID- 10879787
TI  - Refractive errors in Singapore and Xiamen, China--a comparative study in school
      children aged 6 to 7 years.
AB  - PURPOSE: To compare and contrast the prevalence of myopia and other refractive
      errors in Xiamen city, Xiamen countryside (Southern China), and Singapore.
      METHODS: One hundred thirty-two schoolchildren aged 6 to 7 years from Xiamen
      city, 104 from Xiamen countryside, and 146 from Singapore city were recruited to
      join the study. Cycloplegic autorefraction, keratometry, and biometry
      measurements were performed on all children. RESULTS: The prevalence of myopia
      was 12.3% in Singapore city, 9.1% in Xiamen city, and 3.9% in Xiamen countryside.
      The prevalence of astigmatism was higher in Singapore compared with Xiamen. The
      rates of hyperopia and anisometropia were similar in all three locations.
      CONCLUSIONS: The myopia rate in Singapore city was higher than in Xiamen city;
      the lowest rates were found in Xiamen countryside. As the Chinese population from
      all three sites is of similar genetic stock (predominantly from Southern China),
      it is postulated that the differences in myopia rates in these three localities
      may be related to environmental factors.

PMID- 10879788
TI  - Effects of nonius line and fusion lock parameters on fixation disparity.
AB  - PURPOSE: Clinical devices for fixation disparity vary in the size and position of
      the nonius test-lines and in the location of the binocular fusion lock, and
      published results of studies comparing fixation disparity devices also vary. This
      study examined how varying stimulus parameters affects the magnitude of
      horizontal fixation disparity and the precision of nonius alignment in normal
      observers. METHODS: Targets were bright vertical lines presented for 150 ms on an
      oscilloscope and viewed in the dark from 3.95 m through a mirror haploscope. The
      fusion stimulus was either central, peripheral, or central-plus-peripheral.
      Fixation disparity was measured for nonius lines with a fixed vertical separation
      and variable lengths, using the method of constant stimuli. In a second
      experiment, fixation disparity was assessed for vergence demands of 6delta base
      in to 12delta base-out using nonius lines of fixed length and variable vertical
      separations. For comparison, binocular Vernier thresholds and constant errors
      were also assessed. RESULTS: Mean values of fixation disparity are invariant with
      the length and separation of the nonius lines and proximity to the fusion lock,
      over the range of values tested. When measured with a central fusion lock, the
      precision of binocular nonius alignment (vergence variability) worsens if the
      separation between the nonius lines increases beyond approximately 20 min arc.
      Vergence variability is larger with a peripheral fusion lock for small nonius
      line separations and approximately the same as with the central lock for large
      line separations. Fixation disparity and precision were smallest with a central
      plus-peripheral fusion-lock combination. Similar effects of line length and
      separation were found for binocular Vernier. CONCLUSIONS: The finding of
      invariance of fixation disparity with line length for nonius targets < 1degrees
      extends those of earlier findings for larger targets. Because the precision of
      binocular nonius alignment is poorer for large nonius-line separations or with a
      peripheral fusion lock, fixation disparity should be most repeatable when
      measured with a central fusion lock and nonius lines separated by 20 min arc or
      less. However, a peripheral fusion lock and small nonius-line separation may
      provide the most effective diagnostic combination for fixation disparity.

PMID- 10879789
TI  - Saccadic and psychophysical discrimination of double targets.
AB  - Saccades are rapid, conjugate eye movements that shift the foveas onto peripheral
      targets of interest. However, the initial saccades to a peripheral pair of
      targets have been reported to direct the foveas between the targets, despite
      instructions to look at one or the other. This phenomenon, referred to as
      saccadic averaging, can occur for target separations of 10 degrees or more and is
      usually interpreted as evidence that the spatial information available to the
      saccadic system is of inherently poor resolution. We compared the amplitudes of
      initial saccades to single peripheral targets and to pairs of targets, with and
      without prior auditory cues that provided unambiguous information about which
      target represented the saccadic goal. Target duration ranged from 33 to 100 ms,
      followed by a mask that was intended to limit neural processing time. The results
      show that supplementary auditory cues reduce the extent of saccadic averaging to
      target separations as small as 2 degrees. Saccadic averaging is more pronounced
      for targets of brief duration, consistent with the degradation of psychophysical
      resolution that occurs for targets of short duration. We conclude that saccadic
      averaging results in large part because of ambiguity about which of two targets
      represents the saccadic goal and, to a lesser extent, because of the limited time
      that is available before the saccade to process target position.

PMID- 10879790
TI  - The fetus doesn't accept complements.

PMID- 10879791
TI  - Mouse models for spinal muscular atrophy.

PMID- 10879792
TI  - Cerebral autoregulation in sick infants.

PMID- 10879793
TI  - Human IL-2 receptor alpha chain deficiency.
AB  - Profound cellular immunodeficiency occurs as the result of mutations in proteins
      involved in both the differentiation and function of mature lymphoid cells. We
      describe here a novel human immune aberration arising from a truncation mutation
      of the IL-2 receptor alpha chain (CD25), a subunit of the tripartite high
      affinity receptor for IL-2. Decreased numbers of peripheral T cells displaying
      abnormal proliferation but normal B-cell development characterize this
      immunodeficiency. Extensive lymphocytic infiltration of tissues, including lung,
      liver, gut, and bone, is observed, accompanied by tissue atrophy and
      inflammation. Although mature T cells are present, the absence of CD25 does
      affect the differentiation of thymocytes. Although displaying normal development
      of CD2, CD3, CD4, and CD8 expression, CD25-deficient cortical thymocytes do not
      express CD1. Furthermore, they fail to down-regulate levels of bcl-2 and,
      subsequently, apoptosis in the thymus is markedly reduced, resulting in expansion
      of autoreactive clones in multiple tissues.

PMID- 10879794
TI  - Dynamic cerebral autoregulation in sick newborn infants.
AB  - The sick newborn infant is vulnerable to brain injury and impaired cerebral
      autoregulation is thought to contribute to this. Coherent averaging is a method
      of measuring the dynamic cerebral autoregulatory response that is particularly
      suitable for neonates. We used this method in combination with a measure of the
      gradient of the cerebral blood flow velocity (CBFV) response following transient
      blood pressure (BP) peaks to study dynamic autoregulation in infants undergoing
      intensive care. Term and preterm infants at high risk of neurologic injury were
      compared with a control group of infants, also undergoing intensive care.
      Simultaneous video-EEG, CBFV (using transcranial Doppler), and arterial blood
      pressure measurements were obtained intermittently during a study period of at
      least 2 h. Cerebral autoregulatory response curves were constructed for high risk
      and control groups. Intact cerebral autoregulation produces a characteristic
      response consisting of a brief period when CBFV follows arterial blood pressure
      but quickly returns to baseline value. An impaired autoregulatory response shows
      CBFV mirroring the arterial blood pressure curve closely. Thirteen high-risk
      infants, who also had seizures (10 term and 3 preterm) and 12 control infants (6
      term and 6 preterm) were studied. Autoregulation was absent in high-risk term and
      preterm infants. It was also absent in preterm control infants. Term,
      neurologically healthy infants undergoing intensive care have an intact
      autoregulatory response. The constant passive response seen in high-risk infants
      may reflect the severity of the underlying neurologic disease.

PMID- 10879795
TI  - Activation of olfactory cortex in newborn infants after odor stimulation: a
      functional near-infrared spectroscopy study.
AB  - In mammals, perception of smells during the first hours of life is an essential
      prerequisite for adaptation of the newborn to the new extrauterine world.
      Functional magnetic resonance studies have shown that olfactory impression is
      processed in the lateral and anterior orbito-frontal gyri of the frontal lobe.
      Near-infrared spectroscopy (NIRS) can detect changes in oxygenated [Hb O2], and
      deoxygenated [Hb H] Hb during cortical activation. The aim of this study was to
      assess by NIRS olfactory cortex activity in newborn infants receiving olfactory
      stimuli. Twelve males and 11 females were studied when awake at 6 h to 8 d after
      birth. NIRS monitoring was carried out using two optodes placed above the left
      anterior orbito-frontal gyri. Each newborn was exposed for 30 s to two different
      smell stimuli-mother's colostrum and vanilla-and to a negative control, distilled
      water. Changes in Hb concentration were measured over the orbitofrontal region.
      During exposure to vanilla, [Hb O2] increased significantly over the left orbito
      frontal area in all babies. The magnitude of the [Hb O2] increase over the
      illuminated region during colostrum exposure was inversely related to postnatal
      age. We conclude that monitoring Hb changes by NIRS can be valuable in assessing
      olfactory responsiveness in infants.

PMID- 10879796
TI  - Hypocapnia under hypotension induces apoptotic neuronal cell death in the
      hippocampus of newborn rabbits.
AB  - We investigated the adverse effect of hypocapnia on the neonatal rabbit brain.
      Two-week-old Japanese white rabbits were assigned to three groups,
      hyperventilation (H group), ischemia (I group), or hypocapnia with ischemia (HI
      group) and then subjected for 1.5 h with simultaneous measurement of the mean
      arterial blood pressure (MABP) and intracranial Hb concentration changes. Marked
      reductions of PaCO2 and MABP were induced in the hyperventilation-loaded groups
      and the ischemia-loaded groups, respectively. The intracranial oxyhemoglobin and
      total Hb concentrations decreased slightly in the H group and markedly in the I
      and HI groups after the start of experimental protocols, although there were no
      statistical differences between the I and HI groups. Animals were killed at 24 h
      after experiments and then subjected to pathologic examination. Damaged neurons
      with shrunken cell bodies and nuclear changes were found on light microscopic
      examination, mainly in the pyramidal cell layer of the subiculum and cornu
      ammonis 1. The numerical density of damaged neurons was significantly higher in
      the HI group than those in the H or I groups (p < 0.05). These damaged neurons
      were positive on DNA nick end labeling. A DNA ladder was detected on
      electrophoresis with a DNA sample extracted from hippocampal tissue in the HI
      group, but not in the other two groups. On electron microscopic examination, not
      only condensation of the nucleus but also disruption of mitochondria and the cell
      membrane were detected. These results suggested that hypocapnia under hypotension
      might cause neuronal cell death in the hippocampus of neonatal rabbit. Not only
      ischemia but also a metabolic change induced by hypocapnia might contribute to
      this apoptotic neuronal cell damage.

PMID- 10879798
TI  - Early onset heart failure in transgenic mice with dilated cardiomyopathy.
AB  - In children, dilated cardiomyopathy is due to a variety of etiologies and usually
      carries a grave prognosis. The purpose of the present study was to carefully
      follow the progression of events leading to cardiac dilatation and congestive
      heart failure in a dilated cardiomyopathy model in neonatal and juvenile mice.
      These initial steps are often not well characterized. Furthermore, the loss of
      gap junctions and reduced electrical coupling of cardiomyocytes frequently found
      in human cardiomyopathies are also observed in these early stages. By 2 wk of
      age, molecular markers associated with hypertrophy were already altered.
      Cardiomyocyte hypertrophy, reduced connexin43 expression, and decreased
      conduction velocity were apparent by 4 wk, before overt cardiac dysfunction
      (decreased shortening fraction and chamber remodeling) that was not present until
      12 wk of age. Our results show that in this model cardiomyopathic changes are
      present by 2 wk after birth and progress rapidly during the subsequent 2
      postnatal weeks. Combined with the observations of other models of heart disease,
      we suggest that the first 2 wk of postnatal life are absolutely critical for
      normal cardiac development, and events that perturb homeostasis during this
      period determine whether the heart will continue to develop normally. These
      animals exhibit early symptoms of disease including reduced connexin43 and
      conduction defects before impaired cardiac function and demonstrate for the first
      time a temporal association between decreased connexin43 levels and the
      initiation of a contractility deficit that ends in heart failure.

PMID- 10879797
TI  - Beta-defensin expression in human mammary gland epithelia.
AB  - Milk of mammalian species contains a wide spectrum of anti-infectious factors,
      some of which are heat stable. Focusing on recently discovered heat-stable
      antibacterial peptides called defensins, which are expressed in epithelial
      tissues such as airway, skin, and kidney, we hypothesized that mammary gland
      epithelia produce and secrete defensins onto the epithelial surface and into
      milk. Using a reverse-transcription PCR assay, we identified the human beta
      defensin-1 (hBD-1) gene transcript in a human mammary gland epithelial cell line,
      MCF-12A, and in mammary glandular tissue of nine nonlactating women. Epithelial
      cells harvested from milk of lactating women also expressed hBD-1 mRNA. Presence
      of hBD-1 peptide in mammary epithelia was confirmed by immunostaining with an hBD
      1 antibody. In contrast, expression of human beta-defensin-2 was not apparent
      both at mRNA and protein levels. Our findings suggest a biologic role of hBD-1 in
      the human mammary gland.

PMID- 10879799
TI  - Left ventricular alterations in a model of fetal left ventricular overload.
AB  - Congenital aortic coarctation is well tolerated by the fetus because the foramen
      ovale and ductus arteriosus equalize intracardiac and great arteries pressures
      and shunts. The pathologic consequences only emerge after birth with closure of
      the foramen ovale and ductus arteriosus. There is, however, no documentation of
      myocardial effects in utero of the left ventricular (LV) pressure overload
      induced by aortic banding. We investigated whether prenatal aortic banding could
      be detrimental at the structural and/or functional level. The goal of the present
      study was to investigate the cardiac effects of LV pressure overload in a fetal
      lamb model. Nine fetal lambs underwent preductal banding of the aortic arch in
      utero at midgestation (CoA group), whereas their twins underwent sham surgery.
      All fetuses were studied between 27 and 37 d after surgery for LV pressure,
      anatomic and histologic anomalies, and steady state sarcoendoplasmic reticulum
      calcium ATPase (SERCA 2a) mRNA and protein levels and pump activity. Surgery
      resulted in severe aortic coarctation in all the animals in the CoA group and was
      associated with a 65% increase in the LV weight to body weight ratio relative to
      the sham-operated group (p < 0.001). Hemodynamic and histologic studies showed an
      evolutionary pattern depending on duration of the experimental coarctation with a
      shift occurring at 30 d of coarctation. The initial response of cardiomyocytes to
      ventricular overload was hypertrophy of the myocytes, followed by myocyte
      hyperplasia. Compared with sham, there was an apparent decrease in the percentage
      of binucleated cells in the CoA group after 30 d of coarctation. The earliest
      response to LV pressure overload appears to occur at the molecular level. Indeed,
      sarcoendoplasmic reticulum calcium ATPase (SERCA 2a) mRNA levels fell
      significantly to only 28.6% of the sham group value (p = 0.023), independently of
      the duration of coarctation. In the fetal lamb, the pressure overload-induced
      hypertrophy resulting from progressive aortic coarctation leads to hemodynamic
      and lesional abnormalities and slows ontogenic maturation.

PMID- 10879800
TI  - Cardiac contraction affects respiratory airflow in the term newborn infant.
AB  - In studies in the newborn infant, it is often assumed that there are similarities
      in airflow in successive breaths, and, therefore, it is only necessary to measure
      parameters in a small number of breaths. However, other studies have shown
      considerable variability in breathing patterns in successive breaths. It was,
      therefore, decided to examine the variability in the patterns of airflow. By use
      of the trunk plethysmograph, tidal breathing was measured in 20 term newborn
      infants during quiet sleep in the first week after delivery; airflow was
      calculated by differentiating the tidal volume signal. The ECG was also recorded.
      In all infants, it was found that the shapes of both inspiratory and expiratory
      airflow showed considerable differences in successive breaths. Spectral analysis
      of airflow showed the presence of peaks not only in the respiratory rate, as
      expected, but also in the heart rate. In another five infants studied during
      episodes of periodic breathing, small fluctuations in airflow were found during
      the apneic intervals at the same rate as the heart rate. It was concluded that
      this is not an artifact, but that cardiac contraction modulates respiratory
      airflow in the term newborn infant, contributing significantly to breath-to
      breath variability. These cardiac related changes in airflow amount to
      approximately one sixth of the tidal airflow.

PMID- 10879801
TI  - ATP-dependent Ca2+ transport is up-regulated during third trimester in human
      syncytiotrophoblast basal membranes.
AB  - In late gestation, Ca2+ transport across the human placenta must increase in
      response to the demands of accelerating bone mineralization of the fetus. This is
      an ATP-dependent transport against a concentration gradient across the basal or
      the fetal-facing plasma membrane of the syncytiotrophoblast. The aims of the
      present study were to determine the relationship between ATP-dependent Ca2+
      transport and gestational age in the third trimester and to identify the specific
      isoforms of plasma membrane Ca2+ ATPase (PMCA) present in human
      syncytiotrophoblast. Basal membrane vesicles were isolated from normal placentas
      and from placentas obtained from preterm deliveries with no other complications
      (32-37 wk of gestation). We studied the uptake of 45Ca2+ into basal membrane
      vesicles in the absence and presence of ATP by using rapid filtration techniques.
      Western blot was used to assess the protein expression of the PMCA isoforms 1-4.
      Isoforms 1 and 4 of PMCA were identified in basal membrane of human placenta. The
      ATP-dependent Ca2+ transport increased linearly during the third trimester (r =
      0.571, p = 0.0015, n = 28). However, PMCA protein expression was unaltered during
      the same period of gestation. Our results show that PMCA in the fetal-facing
      plasma membrane of the human syncytiotrophoblast is markedly activated toward the
      end of pregnancy. We suggest that these changes are critical in supplying the
      rapidly growing fetus with sufficient Ca2+ for bone mineralization.

PMID- 10879802
TI  - Chronic lung injury in preterm lambs: abnormalities of the pulmonary circulation
      and lung fluid balance.
AB  - Chronic lung disease of early infancy, or bronchopulmonary dysplasia, is a
      frequent complication of prolonged mechanical ventilation after premature birth.
      Pulmonary hypertension and edema are common features of this condition, which is
      often attributed to long-term, repetitive overinflation of incompletely developed
      lungs. The overall objective of this work was to examine the effects on the
      pulmonary circulation and lung fluid balance of different ventilation strategies
      using large versus small inflation volumes in an animal model of bronchopulmonary
      dysplasia. We studied 16 newborn lambs that were delivered prematurely (124+/-3 d
      gestation, term = 147 d) by cesarean section and mechanically ventilated for 3 to
      4 wk. Ten lambs were ventilated at 20 breaths/min, yielding a tidal volume of
      15+/-5 mL/kg, and six lambs were ventilated at 60 breaths/min, yielding a tidal
      volume of 6+/-2 mL/kg. All lambs received surfactant at birth and had subsequent
      surgery for closure of the ductus arteriosus and catheter placement to allow
      serial measurements of pulmonary vascular resistance and lung lymph flow. Chronic
      lung injury, documented by serial chest radiographs and postmortem pathologic
      examination, developed in all lambs irrespective of the pattern of assisted
      ventilation. Pulmonary vascular resistance, which normally decreases during the
      month after birth at term, did not change significantly from the first to the
      last week of study. Lung lymph flow, an index of net transvascular fluid
      filtration, increased with time in lambs that were ventilated at 20 breaths/min,
      but not in lambs ventilated at 60 breaths/min. Lymph protein concentration
      decreased with time, indicative of increased fluid filtration pressure, without
      evidence of a change in lung vascular protein permeability. Postmortem studies
      showed interstitial lung edema, increased pulmonary arteriolar smooth muscle and
      elastin, decreased numbers of small pulmonary arteries and veins, and decreased
      capillary surface density in distal lung of chronically ventilated lambs compared
      with control lambs that were killed either 1 d (same postconceptional age) or 3
      wk (same postnatal age) after birth at term. Thus, chronic lung injury from
      prolonged mechanical ventilation after premature birth inhibits the normal
      postnatal decrease in pulmonary vascular resistance and leads to lung edema from
      increased fluid filtration pressure. These abnormalities of the pulmonary
      circulation may contribute to the abnormal respiratory gas exchange that often
      exists in infants with bronchopulmonary dysplasia.

PMID- 10879803
TI  - Repetitive prenatal glucocorticoids increase lung endothelial nitric oxide
      synthase expression in ovine fetuses delivered at term.
AB  - Antenatal administration of glucocorticoids has been shown to improve postnatal
      lung function after preterm birth in the ovine fetus. Mechanisms of steroid
      induced lung maturation include increased surfactant production and altered
      parenchymal lung structure. Whether steroid treatment also affects lung vascular
      function is unclear. Because nitric oxide contributes to the fall in pulmonary
      vascular resistance at birth, we hypothesized that the improvement of postnatal
      lung function of preterm lambs after treatment with prenatal glucocorticoids may
      be in part caused by an increase in endothelial nitric oxide synthase (eNOS)
      activity. To determine whether glucocorticoid treatment increases lung eNOS
      expression, we measured eNOS protein content by Western blot analysis of distal
      lung homogenates and immunostaining of formalin-fixed lungs from ovine fetuses
      delivered at preterm and term gestation after prenatal administration of
      glucocorticoids. Treatment protocols were followed in which ewes were treated
      with intramuscular betamethasone (0.5 mg/kg) at single or multiple doses at
      weekly intervals, and fetuses were delivered at 125, 135, or 145 d gestation. All
      groups were compared with saline-treated controls. Western blot analysis of whole
      lung homogenates demonstrated a 4-fold increase in eNOS protein content in lambs
      treated with repetitive doses of glucocorticoids and delivery at term (145 d; p <
      0.002). In addition, a small increase in lung eNOS protein content was seen in
      lambs treated with a single dose of betamethasone at 128 d gestation with
      delivery at 135 d gestation. In comparison with control animals, there were no
      differences in lung eNOS content from the remaining lambs treated with
      glucocorticoids when delivery occurred at preterm ages (125 and 135 d).
      Immunostaining showed eNOS predominantly in the vascular endothelium in all
      vessel sizes. Pattern of staining was not altered by treatment with antenatal
      glucocorticoids. We conclude that maternal treatment with glucocorticoids
      increases lung eNOS content after multiple doses and delivery at term gestation.
      We speculate that antenatal glucocorticoids may up-regulate eNOS but that the
      timing and duration of steroid administration appears to be critical to this
      response.

PMID- 10879804
TI  - Protein carbonyls and lipid peroxidation products as oxidation markers in preterm
      infant plasma: associations with chronic lung disease and retinopathy and effects
      of selenium supplementation.
AB  - The purpose of this study was to determine whether protein carbonyls and the
      lipid peroxidation product malondialdehyde (MDA) are elevated in plasma from very
      low birth weight (<1500 g) infants, whether they are affected by selenium
      supplementation, and whether they are associated with poor respiratory outcome or
      retinopathy. The study group comprised 173 infants enrolled in a randomized
      controlled trial of selenium supplementation. Plasma samples, collected before
      randomization, at 7 and 28 d after birth, and at 36 wk postmenstrual age, were
      analyzed for protein carbonyls and total MDA. Respiratory outcome was assessed as
      oxygen requirement at 28 d of age or 36 wk postmenstrual age and as number of
      days on oxygen. Protein carbonyl concentrations in very low birth weight infants
      were significantly higher than for adults but lower than for cord blood from term
      infants. Median values decreased significantly by 28 d, and there was no
      relationship with birth weight. MDA concentrations in very low birth weight
      infants overlapped the ranges for healthy adults and cord blood from term
      infants. They correlated positively with birth weight at 28 d but not at other
      times. Supplementation almost doubled plasma selenium concentrations, but
      carbonyls and MDA did not differ between the supplemented and unsupplemented
      groups. There were no significant differences in oxidant marker levels in infants
      who did or did not develop chronic lung disease or retinopathy. Protein carbonyls
      and MDA measurements in plasma do not show evidence of systemic oxidative stress
      in <1500-g infants and are not affected by selenium supplementation. Oxidative
      injury at sites such as the lung may be important in prematurity, but markers
      from such sites must be measured to relate to outcome and antioxidant
      supplementation.

PMID- 10879805
TI  - Effect of antenatal dexamethasone treatment on Ca2+-dependent nitric oxide
      synthase activity in rat lung.
AB  - We investigated the effects of dexamethasone on nitric oxide synthase activity,
      nitrate/nitrite concentration, and cGMP concentration in the lungs of premature
      and full-term neonate rats. Dexamethasone or vehicle alone was administered to
      the mother (1 mg/kg/d, s.c., 2 d), and the neonate was killed 24 h after birth.
      Ca2+-dependent nitric oxide synthase activity and nitrate/nitrite and cGMP
      concentrations in lungs of dexamethasone-treated neonates, both premature and
      full-term, were significantly higher than those in the lungs of the control rats.
      Ca2+-dependent nitric oxide synthase activity, nitrate/nitrite concentration, and
      cGMP concentration in the lungs of control rats showed developmentally associated
      increases during late gestation and in the early postnatal period. The activation
      of the nitric oxide synthasenitric oxide-cGMP system by antenatal dexamethasone
      treatment may be related to the improvement of pulmonary function by antenatal
      glucocorticoid therapy to minimize respiratory distress syndrome.

PMID- 10879806
TI  - Mechanisms of reduced body growth in the pubertal feminized male rat: unbalanced
      estrogen and androgen action on the somatotropic axis.
AB  - It is well known that the sex difference in body growth at puberty is modulated
      by a complex interplay between sex steroids and somatotropic axis; however, the
      exact role played by sex steroids remains a matter of controversy. The aim of
      this study was to assess the mechanisms by which sex steroids regulate body
      growth during pubertal development. Flutamide, a non-steroid-blocking androgen
      receptor, was subcutaneously administered to 30-d-old male Wistar rats for 4 wk.
      The blockade of the androgen receptor led to a marked elevation in serum
      testosterone and an increment in serum estradiol. Flutamide administration
      decreased body weight gain, serum IGF-I levels, hepatic IGF-I mRNA, and GH
      receptor mRNA content. There were no significant changes in serum GH
      concentration, pituitary GH reserve, and pituitary GH mRNA content. Flutamide
      lowered hypothalamic somatostatin mRNA content and augmented hypothalamic
      immunoreactive somatostatin stores, but did not alter hypothalamic immunoreactive
      GH-releasing factor stores. Our findings indicate that during pubertal
      development of the male rat, the imbalance between androgen and estrogen actions
      determines an abnormal somatic growth, which is at least partly exerted through
      the peripheral or hepatic modification of the somatotropic axis that occurs under
      the high or exclusive action of estrogens. Potential implication of coincident
      sex-specific regulated mode of pulsatile GH secretion cannot be excluded from
      this random serum GH sample study.

PMID- 10879807
TI  - Plasma concentrations of the carboxyterminal propeptide of type I procollagen
      (PICP) in preterm neonates from birth to term.
AB  - Carboxyterminal propeptide of type I procollagen (PICP), a marker of bone
      formation, has not yet been studied in preterm infants. In this study, PICP
      concentrations were measured longitudinally for 12 wk after birth using the ELISA
      technique in 43 preterm infants with a gestational age (GA) ranging from 24-29 wk
      and in 35 preterm infants with a GA ranging from 30-34 wk. PICP values in these
      preterm infants were higher than in children and adults. In cord plasma of
      preterm infants there was a significant gender difference, with higher PICP
      concentrations in male infants. A characteristic longitudinal pattern with an
      initial decrease during the first 3 postnatal days followed by a rapid increase
      from d 7 to d 28 was seen in both groups. Regarding the individual gestational
      ages, all preterm infants attained maximum PICP concentrations around 36 wk
      postmenstrual age. Multiple regression analysis revealed cord plasma PICP
      concentrations were significantly associated with GA, birth weight, sex, and IGF
      I. A significant correlation between PICP concentrations and GA was seen at wk 1
      4 and between PICP concentrations and protein intake at wk 1. Body weight and
      energy intake were shown to exert a significant effect on the PICP concentrations
      at 2 wk. The collected data in preterm infants may serve further studies
      evaluating PICP as a marker for bone formation and growth in very low birth
      weight premature infants.

PMID- 10879808
TI  - Reduction of hypoxic-ischemic brain swelling in the neonatal rat with PAF
      antagonist WEB 2170: lack of long-term protection.
AB  - Platelet activating factor (PAF) is an inflammatory lipid mediator released by
      ischemic brain. Our objectives were to use an inhibitor of PAF that does not
      readily cross the blood-brain barrier, WEB 2170, to study the role of
      intravascular PAF on brain swelling and subsequent brain atrophy in a neonatal
      rat model of hypoxic-ischemic brain injury. We injured the right cerebral
      hemisphere of 7-d-old rats by ligating the right common carotid artery and
      exposing the rats to 8% oxygen for 2.25 h. Forty-two rats received saline or the
      PAF antagonist WEB 2170, 1 h before hypoxia. We found that WEB 2170 pretreatment
      reduced swelling by 64% (p = 0.003). In contrast, treatment immediately after
      hypoxic-ischemic injury did not reduce swelling. In two additional experiments
      involving 103 rats, we found that pretreatment or repeated doses of PAF
      antagonist before and after hypoxic-ischemic injury did not reduce atrophy. We
      also found that the brain-penetrating PAF antagonist, BN 52021, did not prevent
      atrophy in our Wistar rat model. In conclusion, we were unable to reduce long
      term brain injury with either PAF antagonist. WEB 2170 pretreatment reduced brain
      swelling by 64% without reducing atrophy. This suggests that although brain
      swelling may accompany cerebral infarction, it does not contribute to the
      pathogenesis of infarction and subsequent atrophy in the neonatal rat. The
      ability to reduce early postischemic brain swelling without reducing atrophy may
      be particularly unique to the immature animal with a compliant skull.

PMID- 10879809
TI  - Ureaplasma urealyticum-induced production of proinflammatory cytokines by
      macrophages.
AB  - Ureaplasma urealyticum is relatively common in the respiratory tract of very low
      birth weight infants and has been hypothesized to be involved in the development
      of chronic lung disease. The purpose of this study was to investigate whether U.
      urealyticum could stimulate macrophages to produce proinflammatory cytokines in
      vitro, which are early pathologic changes in the lung during the development of
      chronic lung disease. A human monocytic cell line (THP-1) differentiated to
      macrophages, a rat alveolar macrophage cell line (Nr8383), and human lung
      macrophages from tracheobronchial aspirate fluid in preterm infants were exposed
      to U. urealyticum antigen for 24 h. The protein levels of human IL-6, tumor
      necrosis factor-alpha (TNF-alpha), and rat TNF-alpha were measured with ELISA.
      Rat IL-6 was analyzed with a specific bioassay. The mRNA levels of these
      cytokines were detected by reverse transcriptase-PCR. The production of TNF-alpha
      and IL-6 increased after stimulation with U. urealyticum in both the human and
      rat macrophage cell lines. In tracheobronchial aspirate fluid macrophages, U.
      urealyticum increased the production of TNF-alpha from 14 to 84% and IL-6 from 46
      to 268% above control levels. U. urealyticum also induced gene expression of TNF
      alpha and IL-6. In conclusion, U. urealyticum could be an important factor in the
      development of chronic lung disease because of its ability to induce alveolar
      macrophage proinflammatory cytokine production.

PMID- 10879810
TI  - Interaction between pulmonary surfactant and vernix: a potential mechanism for
      induction of amniotic fluid turbidity.
AB  - The development of amniotic fluid turbidity during the third trimester is a known
      marker of fetal lung maturity. We hypothesized that this turbidity results from
      detachment of vernix caseosa from the fetal skin secondary to interaction with
      pulmonary-derived phospholipids in the amniotic fluid. To test this hypothesis,
      we exposed vernix to bovine-derived pulmonary surfactant over a physiologically
      relevant concentration range. Ten milligrams of vernix was evenly applied to the
      interior walls of 1.5-mL polypropylene microfuge tubes. Surfactant phospholipids
      were added to the tubes followed by slow rotation at 37 degrees C overnight. The
      liquid was decanted and spectrophotometrically analyzed at 650 nm to detect
      solution turbidity due to vernix detachment and/or emulsification. Increasing
      concentrations of surfactant phospholipids produced a dose-dependent increase in
      solution turbidity. A phospholipid mixture closely approximating natural
      pulmonary surfactant but devoid of surfactant-associated proteins yielded no
      increase. In other studies, the flow properties of vernix were studied in a Haake
      flow rheometer at 23 degrees C and 37 degrees C. There was a marked temperature
      dependent effect with lower stress required to elicit flow at 37 degrees C
      compared with 23 degrees C. This temperature dependence was also demonstrated in
      the turbidity assay with a 124% increase in turbidity at body temperature
      compared with room temperature. We conclude that under in vitro conditions,
      pulmonary surfactant interacts with vernix resulting in detachment from a solid
      phase support. We speculate that in utero, this phenomenon contributes to the
      increase in amniotic fluid turbidity that is observed near term.

PMID- 10879811
TI  - Diverse, region-specific effects of addition of arachidonic and docosahexanoic
      acids to formula with low or adequate linoleic and alpha-linolenic acids on
      piglet brain monoaminergic neurotransmitters.
AB  - Differences in visual, auditory, and learning tasks have been reported for
      infants and animals given diets varying in omega-3 fatty acids, but the
      neurobiochemical basis for these changes is unclear. This study investigated the
      effect of feeding formula with 0.8% energy C18:2omega-6 + 0.05% C18:3omega-3
      (low), or 8.3% C18:2omega-6 + 0.8% C18:3omega-3 (adequate), with and without 0.2%
      energy arachidonic acid (C20:4omega-6) and 0.16% docosahexanoic acid (C22:6omega
      3), on monoaminergic neurotransmitters in different brain regions of piglets fed
      formula from birth to 18 d. The amount of C18:2omega-6 + C18:3omega-3 fed in
      formula had a significant effect on frontal cortex dopamine, 3,4
      dihydroxyphenylacetic acid, homovanillic acid, serotonin, and 5
      hydroxyindolacetic acid; striatum serotonin and inferior colliculus serotonin,
      resulting in lower concentrations in piglets fed the low compared with adequate
      C18:2omega-6 + C18:3omega-3 formula. Inclusion of arachidonic acid and
      docosahexanoic acid in the low, but not in the adequate, C18:2omega-6 +
      C18:3omega-3 formula resulted in increased concentrations of all monoamines in
      the frontal cortex, and in striatum and inferior colliculus serotonin. Feeding
      arachidonic acid and docosahexanoic acid in the formulas increased dopamine and 5
      hydroxyindolacetic acid in superior and inferior colliculus, areas related to
      processing and integration of visual and auditory information. Higher dopamine
      and 5-hydroxyindolacetic acid were found in these regions even when arachidonic
      acid and docosahexanoic acid were added to the C18:2omega-6 + C18:3omega-3
      adequate formula. This study suggests that functional changes among animals and
      infants fed diets varying in omega-6 and omega-3 fatty acids may involve altered
      neurotransmitter metabolism.

PMID- 10879812
TI  - Butyltins in shellfish, finfish, water and sediment from the Coos Bay estuary
      (Oregon, USA).
AB  - Butyltin was measured in tissue, water and sediment samples collected throughout
      Coos Bay estuary between 1986 and 1997. Butyltin-induced shell deformation in
      commercial oysters prompted this assessment. Butyltins are released from
      tributyltin oxide (TBTO)-containing boat paint. Clams from three sites contained
      tributyltin (TBT) levels ranging from 168 to 457 microg/kg in 1992-1994.
      Consequently, Oregon Health Division (OHD) issued a shellfish consumption
      advisory in 1995; it was rescinded in 1997 after US Environmental Protection
      Agency (EPA) revised the TBTO oral reference dose (RfD). The revised RfD changed
      the tissue screening level from 112 to 1120 microg TBT/kg. Fifty percent of
      sediment samples collected during 1991-1997 and analyzed for total butyltins
      (TotBT) exceeded the Puget Sound Dredge Disposal Analysis Screening Level (PSDDA
      SL) of 73 microg TBT/kg dw. TotBT at three shipyards selected for site assessment
      by EPA ranged from 24 to 68,613 microg/kg dw. Sediment and tissue butyltins have
      been decreasing in all but one area of the estuary.

PMID- 10879813
TI  - Proposals to overcome limitations in the EU chemical risk assessment scheme.
AB  - The notification of new chemicals in the European Union requires a risk
      assessment. A Technical Guidance Document (TGD) was prepared for assistance. The
      TGD proposes QSARs, regressions and models from various sources. Each method has
      its own range of applicability and its own restrictions. Regressions used in the
      assessment of indirect human exposure have a common regression range from log
      K(OW), 3.0-4.6. Most models are compartment models, which do not consider a
      spatial distribution of the chemical, and were originally developed for non
      dissociating, lipophilic persistent chemicals with measurable vapor pressure.
      Taking this into account, the TGD is only applicable for a minority of chemical
      classes. Dissociating compounds, ions, polar and very non-polar compounds do not
      belong to them. The effect of mixtures cannot be considered, except for
      hydrocarbons. Using the example of plant uptake, it is shown that in certain
      cases uptake is underestimated by the model due to processes not considered. This
      may lead to a wrong security in risk assessment. To overcome these limitations, a
      set of alternative models with different application ranges should be developed.
      When no applicable method is available, it might be better not to use a model at
      all instead of an inadequate model, and look for other sources of information.

PMID- 10879814
TI  - Interaction of bisphenol A with rat hepatic cytochrome P450 enzymes.
AB  - The effect of bisphenol A (BPA) on the kinetics of cytochrome P450 (P450)
      dependent monooxygenases in rat liver microsomes was studied. Testosterone 16beta
      hydroxylase (TS16BH) and testosterone 2alpha-hydroxylase (TS2AH) activities were
      extensively inhibited by BPA at 100 microM (69% and 74%, respectively). The
      inhibition type was mixed for both P450-dependent monooxyganases. The Ki of
      TS16BH and TS2AH from Lineweaver-Burk plots were 25.9 and 24.9 microM,
      respectively. The activities of acetanilide 4-hydroxylase (AA4H), 7
      ethoxycoumarin O-deethylase (ECOD), bufuralol 1'-hydroxylase (BF1'H),
      chlorzoxazone 6-hydroxylase (CZ6H) and testosterone 6beta-hydroxylase (TS6BH)
      were also effectively inhibited by BPA at 100 microM (43-52%). The inhibition
      type of these P450-dependent monooxygenases was mixed or uncompetitive, and the
      K(i)s (50.5-88.5 microM) were higher than those of TS16BH and TS2AH. By contrast,
      the values of IC50 and Ki of testosterone 7alpha-hydroxylase (TS7AH) and lauric
      acid omega-hydroxylase (LAOH) for BPA were >1000 microM. These results suggest
      that BPA interacts with rat hepatic CYP1A2, CYP2A2, CYP2B2, CYP2C11, CYP2D1,
      CYP2E1 and CYP3A2 in vitro.

PMID- 10879815
TI  - Chemical and biological profiles of sediments as indicators of sources of
      genotoxic contamination in Hamilton Harbour. Part I: analysis of polycyclic
      aromatic hydrocarbons and thia-arene compounds.
AB  - Bottom sediment and suspended sediment samples from Hamilton Harbour (western
      Lake Ontario) and from a major tributary were profiled using polycyclic aromatic
      hydrocarbons (PAH) and thia-arenes as source apportionment tracers. Ratios of
      selected PAH and ratios of monomethyl and dimethyl/ethyl dibenzothiophenes to the
      parent dibenzothiophenes were calculated. Thia-arene and PAH profiles of Standard
      Reference Material SRM 1649 (urban dust/organics), SRM 1650 (diesel), SRM 1597
      (coal tar), Hamilton coal tar and a composite Hamilton air particulate sample
      provided source sample data. The gas chromatography-mass spectrometry (GC-MS)
      chromatograms of all sample extracts were dominated by homocyclic PAH but
      interpretation of PAH profiles with respect to source was difficult. In contrast,
      thia-arene analyses revealed more distinct differences in profiles of samples
      collected in different areas of the harbour, including the tributary. These
      results indicated that areas of coal tar-contaminated sediment are potential
      contributors to the overall contaminant burden of sediments and suspended
      sediments in Hamilton Harbour. These data also indicated that contaminants
      related to mobile combustion sources were entering the harbour via a major
      tributary.

PMID- 10879816
TI  - Chemical and biological profiles of sediments as indicators of sources of
      contamination in Hamilton Harbour. Part II: bioassay-directed fractionation using
      the Ames Salmonella/microsome assay.
AB  - Bottom sediment and suspended sediment samples from Hamilton Harbour (western
      Lake Ontario) and from a major tributary were profiled using a bioassay-directed
      fractionation approach. Sample extracts were fractionated using an
      alumina/Sephadex gel clean-up procedure to afford non-polar aromatic fractions
      which were characterized using chemical analyses and the Ames/microsome bacterial
      assay in Salmonella typhimurium strains YG1025 with the addition of oxidative
      metabolism (S9), and YG1024 without S9. Non-polar aromatic fractions of selected
      samples were separated by normal phase HPLC into 1-min fractions which were
      subjected to bioassay analyses. The bioassays using strain YG1025+S9, a TA100
      type strain, were performed to assess genotoxicity arising from the presence of
      polycyclic aromatic hydrocarbons (PAH). Fractions which exhibited mutagenic
      activity contained PAH with molecular masses of 252, 276 and 278 amu; these
      fractions contained over 80% of the genotoxicity attributable to PAH. Individual
      compounds identified using Gas Chromatography-Mass Spectrometry analyses in these
      active fractions included benzo[a]pyrene, indeno[cd]pyrene and
      dibenz[a,h]anthracene. The YG1025+S9 mutagenic activity profiles were similar for
      all samples. Mutagenic activity profiles generated using strain YG1024-S9, a TA98
      type strain sensitive to compounds characteristic of mobile source emissions,
      were very different. The mutagenic activities in strain YG1024-S9 were greatest
      for harbour-suspended sediment samples collected from sites impacted by a major
      tributary. Suspended sediments collected near areas known to contain high levels
      of coal tar-contamination in the bottom sediments contained higher levels of
      genotoxic PAH than suspended sediments collected from other areas of the harbour.

PMID- 10879817
TI  - Influence of special surfactants on the microbial degradation of mineral oils.
AB  - Various surfactants belonging to the group of fatty acid-acylated amino acids
      were tested for their ability to accelerate the microbial degradation of mineral
      oil. Of the lauric acid-acylated amino acids, aliphatic acids and histidine were
      found to be the most suitable. By the aid of these compounds additional 20-60% of
      a residual oil fraction could be degraded. The longer the chain of the fatty acid
      moiety, the more effective the surfactants are. Natural L-amino acids were more
      effective than their D-configuration. Since the special surfactants are easily
      biologically degradable, multiple replenishment is required in long-term
      experiments. The faster, more complete degradation of mineral oil is caused
      solely by interfacial activity; the growth of biomass due to the function of
      surfactants as substrate had no effect.

PMID- 10879819
TI  - The biodegradability and microbial toxicity testing of lubricants--some
      recommendations.
AB  - In recent years there has been a growing demand for information on the
      biodegradability (fate) and microbial toxicity (effects) of lubricants. This has
      been driven by the need to comply with environmental legislation and to meet the
      requirements of ecolabelling schemes, standards and customer specifications for
      'environmentally acceptable' lubricants. This paper describes suitable approaches
      for generating this information under a variety of environmental conditions (e.g.
      aerobic, anaerobic, freshwater, marine), gives examples of the results obtained
      and discusses their interpretation. Recommendations on the use of each test are
      made.

PMID- 10879818
TI  - Algal growth inhibition: effect of the choice of growth rate or biomass as
      endpoint on the classification and labelling of new substances notified in the
      EU.
AB  - From the complete base set notifications of new substances currently available,
      we have investigated what effects the choice of using growth rate or biomass in
      the algal growth inhibition test has on the relative sensitivity of the three
      aquatic toxicity tests. Both parameters derived from the algal test were more
      sensitive than either fish or Daphnia tests. Changes in the classification of
      substances after the removal of either algae, Daphnia or fish data from the base
      set, when applying current legal practice, occur in 22.9%, 6.6% and 4.8% of the
      notifications, respectively. When always using growth rate as a parameter, these
      numbers change to 15.4%, 9.2% and 7.2%, respectively.

PMID- 10879820
TI  - Effect of a triazole fungicide on the cellulose decomposition by the soil
      microflora.
AB  - The effect of flutriafol on the cellulose decomposition was studied in the
      laboratory as a dose-response experiment using a trade marked formulation.
      Cellulose degradation rates were determined by the weight loss from cellulose
      filter disks buried in soil samples and by the CO2 evolved during batch
      incubation experiments. To amounts recommended for field applications and ten
      fold these dosages, flutriafol did not affect the cellulose decomposition ability
      of the soil-microflora. Highest dosages provoked an initial inhibitory effect,
      followed by a stimulation in cellulolytic activity. Possible reasons for the dose
      response relationship were changes in the soil microflora in favour of bacteria,
      indicating the importance of the persistence and repeated applications of
      flutriafol.

PMID- 10879821
TI  - Alimentary lead intake of adults in Thuringia/Germany determined with the
      duplicate portion technique.
AB  - The daily lead intake in Germany in 1996 was studied using the duplicate portion
      technique. The study was carried out in four towns in Thuringia (Jena, Ronneburg,
      Rositz, Steudnitz), in which volunteers collected all foods and beverages over 7
      consecutive days. The mean lead content of consumed food and beverages was 66 and
      55 microg/kg dry matter for women and men, respectively; the average lead intake
      was 19 microg/day for both, women and men. In relation to body weight (b.w.) the
      intake for women was 283 ng/kg and for men 242 ng/kg b.w. These values are well
      below the WHO limit. An oral lead exposure of the adult population of
      Thuringia/Germany can be excluded.

PMID- 10879822
TI  - The effect of dimethoate and cypermethrin on soil-dwelling beetles under semi
      field conditions.
AB  - The effect of cypermethrin and dimethoate exposure on soil-dwelling beetles, in
      spring barley at different growth stages, of doses of up to eight times maximum
      field application rate has been investigated. Doses up to eight times maximum
      field application rate of cypermethrin did not have any acute effects on larger
      beetles, such as P. melanarius and C. erratus. Small beetles (A. bilineata, A.
      dorsale, B. lanpros, B. obtusum) were not harmed by doses up to two times maximum
      field application rate. T. hypnorum was affected at maximum field rate.
      Dimethoate at maximum field application rate harmed all species, but in
      particular the smaller species. When dimethoate was applied in high foliage
      density fields in the summer, very severe acute effects on spring breeding
      beetles were found. In the autumn, when only a low crop cover existed, this very
      high effect was not observed. The severe effect in the summer may be explained by
      the mode of action of dimethoate on 'old beetles'. The observed high toxic effect
      of dimethoate on spring breeders in the summer is expected only to have limited
      effect on the population, because the spring breeders at this time of the year
      have finished their egg depositing in the soil.

PMID- 10879823
TI  - The effect of thymol and its derivatives on reactions generating reactive oxygen
      species.
AB  - The effects of thymol (TOH), thymoquinone (TQ) and dithymoquinone (TQ2) on the
      reactions generating reactive oxygen species (ROS) such as superoxide anion
      radical (O2*-), hydroxyl radical (HO*) and singlet oxygen (1O2) were tested using
      the chemiluminescence (CL) and spectrophotometry methods. All tested compounds
      acted as scavengers of various ROS. The rate constant of 1O2-dimols quenching by
      thymol was calculated.

PMID- 10879824
TI  - A simple bacterial index for relative water quality: preliminary application in
      the Orbetello lagoon (Tuscany, Italy).
AB  - A simplified fingerprint, elaborated upon heterotrophic bacterial charge and
      conventional faecal coliforms (FCs) was used to measure the relative quality of
      the waters in the western basin of the Orbetello lagoon (Tuscany, Italy).
      Different bacteriological parameters were combined, after standardisation,
      obtaining "iso-quality" lines. The-final image of the lagoon exhibits different
      pollution levels, with a relative minimum in the central area.

PMID- 10879825
TI  - Potential antitermite compounds from Juniperus procera extracts.
AB  - Thin layer chromatography (TLC) analysis revealed that destructive distillation
      of Juniperus procera tree gave ten major components, whereas Croton megalocarpus
      tree yielded five components. This was confirmed by gas chromatography (GC). The
      components were isolated by column chromatography and analysed using infrared,
      ultra-violet, visible and mass spectroscopy (MS) techniques. The whole extract
      was about 30.3% of the starting material (sawdust) and consisted of 77.5% water
      and 22.5% oily reddish-brown layer. The extracts had alcoholic and phenolic
      compounds together with acids. Cedrol, a tertiary tricyclic alcohol, was found to
      be in the greatest proportion in the oily layer. IR spectra with a peak beyond
      3000 cm(-1), UV-VIS absorption maxima at 230 nm and mass spectra with m/e 204
      suggested the presence of cedrene in the extract.

PMID- 10879826
TI  - Chromium (VI) accumulation reduces chlorophyll biosynthesis, nitrate reductase
      activity and protein content in Nymphaea alba L.
AB  - Plants of Nymphaea alba L. grown at various levels of chromium (VI) ranging from
      1 to 200 microM accumulated chromium in concentration and duration-dependent
      manner. At all Cr levels, chromium accumulation by various plant tissues followed
      the order roots > leaves > rhizomes. Approximately 93% of total chromium present
      in the medium was accumulated by plants at lowest conentration (1 microM) used in
      the experiment. Chromium-induced toxicity appears at 1 microM chromium resulting
      in the build-up of delta-aminolevulinic acid (ALA) and reduced activities of
      delta-aminolevulinic acid dehydratase (ALAD) and nitrate reductase (NR), total
      chlorophyll (Chl) and protein contents. Ch1a was more sensitive than Ch1b to
      chromium toxicity. It could be inferred that chromium toxicity is not located at
      the level of ALA synthesis, but, probably at the ALAD activity which was more
      severely affected during chlorophyll biosynthesis. Finally, impaired chlorophyll
      biosynthesis resulted in reduced total chlorophyll content.

PMID- 10879827
TI  - Isolation of MFO inducers from tissues of white suckers caged in bleached kraft
      mill effluent.
AB  - White sucker (Catostomus commersoni) caged for 3 days in a bleached kraft mill
      effluent (BKME) stream had elevated mixed function oxygenase (MFO) activities 15
      90 fold those of fish caged in a reference stream. Liver composites of male and
      female fish were ground and extracted with dichloromethane (DCM), methanol or 50%
      DCM/methanol, and tested for MFO activity in rat hepatoma cells (H4IIE). There
      was no difference in the potency of H4IIE EROD induction among the three
      solvents, so DCM extracts were split into 31 fractions using reverse phase high
      pressure liquid chromatography (HPLC). H4IIE MFO activity was elevated in several
      fractions, with three early peaks and several later peaks of induction,
      indicating several classes or compounds causing MFO induction were present in the
      fish livers. Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs) and chlorinated diphenylethers (CDPEs) were detected in
      several late-eluting fractions, but concentrations were not high enough for these
      compounds to be solely responsible for the observed induction. Induction by liver
      extracts decreased as cell exposure times increased (24, 48 or 72 h), suggesting
      that some inducers were more easily metabolized and eliminated from the H4IIE
      cells. In contrast, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2378-TCDD) had similar
      potency over 24, 48 and 72 h, as it was relatively resistant to metabolism.

PMID- 10879828
TI  - Can adsorption isotherms predict sediment bioavailability?
AB  - The adsorption and desorption of 2,4-dichlorophenol (DCP) and pentachlorophenol
      (PCP) were studied for a range of synthetic particles, a dimethylditallowammonium
      exchanged clay and a natural sediment. The synthetic particles were Dowex 1X8400,
      Toyopearl Phenyl 650M and Toyopearl SP 650M. The bioaccumulation of the DCP and
      PCP from these particles was then studied using the oligochaete, Lumbriculus
      variegatus. There is a correlation between contaminant-particle interactions, as
      determined from adsorption and desorption isotherms, and bioaccumulation.
      Bioaccumulation by L. variegatus was found to be highest from the systems where
      differences in the classification of adsorption and desorption isotherms were
      observed.

PMID- 10879829
TI  - Long-term increased bioaccumulation of mercury in largemouth bass follows
      reduction of waterborne selenium.
AB  - Average mercury concentrations in largemouth bass from Rogers Quarry in east
      Tennessee were found to increase steadily following the elimination of selenium
      rich discharges of fly ash to the quarry in 1989. From 1990 to 1998, mean mercury
      concentrations (adjusted to compensate for the covariance between individual fish
      weight and mercury concentration) in bass rose from 0.02 to 0.61 mg/kg. There was
      no indication that the rate increase was slowing or that mercury concentrations
      in fish were approaching a plateau or steady state. Mean selenium concentrations
      in bass declined from 3 to 1 mg/kg over the first five years of the study, but
      remained at 1-1.5 mg/kg (about twice typical concentrations in bass from local
      reference sites) for the last three years of the study. Gross physical
      abnormalities were common in fish from the site in the first three years after
      elimination of fly ash discharges but disappeared after two more years. Although
      it remains possible that other chemical or physical changes related to fly ash
      disposal in the system were associated with increased mercury bioaccumulation,
      the most likely explanation is that selenium played a critical role. It appears
      as though aqueous selenium enrichment was capable of having a profound effect on
      mercury bioaccumulation in this system but at the cost of causing a high
      incidence of gross abnormalities in fish. However, it is possible that selenium
      concentrations between the national ambient water quality criterion for the
      protection of aquatic life, 5 microg/l, and that now found in Rogers Quarry (<2
      microg/l) could reduce mercury bioaccumulation without causing adverse effects on
      aquatic biota and fish-eating wildlife.

PMID- 10879830
TI  - Patterns of organochlorine pesticide contamination in neotropical migrant
      passerines in relation to diet and winter habitat.
AB  - Eleven species of Neotropical migrant passerines collected in Illinois (USA)
      during May 1996, were analyzed for the presence of organochlorine (OC)
      pesticides. At least one of five OC pesticide residues was detected in 66 of 72
      birds, representing all species examined. The contaminants most frequently
      detected were p,p'-DDE, dieldrin and heptachlor epoxide, all of which were
      present in the 10-30 ng/g range. Insectivores had significantly higher levels of
      these compounds than did non-insectivores, while there was no significant main
      effect of winter habitat (forest and scrub). Future research on OC pesticide
      contamination in resident New World passerines may allow more accurate
      predictions regarding the sources of contamination in Neotropical migrants.

PMID- 10879831
TI  - Radiochemistry: inconvenient but indispensable
AB  - Radiochemistry has always been and still is a crucial tool in the field of
      radionuclide determination, both for high and low level works; this holds
      particularly in the case of alpha and beta emitters. Requests to the analyst are
      increasingly demanding in terms of performance (detection limit, reliability,
      accuracy, precision,...), but also of economy (cost, time,...) and of flexibility
      with respect to sample types. In general, chemical and radiochemical analyses
      consist of four main steps: sample pre-treatment including pre-concentration,
      dissolution and/or digestion, separation of analytes from the matrix and from
      each other, transformation of the separated fraction into a source suited for
      measurement, determination of the amount or the activity of the analytes. The
      required combination of sub-procedures is determined by the analytes under
      investigation, their absolute and relative amounts, the matrix composition and by
      the performance required. IRMM's Analytical Chemistry Unit started several years
      ago to develop, adapt and/or validate various radiochemical methods and
      procedures, and apply these to different measurement tasks. This paper gives an
      overview on recent and ongoing activities.

PMID- 10879832
TI  - Traceability of measurements of radioactivity and of amount of substance
AB  - Comparability of measurement results in space and time are highly desirable to
      observe whether differences are real, whether concordance of results is real and
      whether trends over time of the quantity measured, are significant. The
      metrological way to achieve this, is to make results 'traceable' to a common
      'stated reference' (definition in the Vocabulaire International de Metrologie
      VIM). This 'stated reference' should be (the value of) the relevant SI unit
      wherever and whenever possible. The latest traceability concepts for results of
      measurements of radioactivity and amount of substance are presented and
      critically compared for their similarity. Transparent and simple pictures of
      traceability chains are given, respecting the VIM definition.

PMID- 10879833
TI  - Low level radioactivity measurement in support of the CTBTO. Comprehensive
      Nuclear-Test-Ban Treaty Organization
AB  - Radioactivity measurements, together with three other technologies: seismic,
      hydroacoustic and infrasound, are able to detect, identify and locate nuclear
      explosions down to 1 kt. Eighty stations worldwide, with a sensitivity of 10-30
      microBq/m3 for 140Ba and 1 mBq/m m3 for 133Xe, have been or will be established
      in order to provide an estimated 90% detection probability within 10 days after a
      nuclear explosion. The equipment for manual stations--the high volume samplers,
      high sensitivity HPGe detectors and auxiliary measurement systems, as well as the
      automatic stations are described. The problems and results of atmospheric
      transport, site location as well as equipment and station operation are
      discussed.

PMID- 10879834
TI  - Accelerator mass spectrometry analyses of environmental radionuclides:
      sensitivity, precision and standardisation
AB  - Accelerator Mass Spectrometry (AMS) is the analytical technique of choice for the
      detection of long-lived radionuclides which cannot be practically analysed with
      decay counting or conventional mass spectrometry. AMS allows an isotopic
      sensitivity as low as one part in 10(15) for 14C (5.73 ka), 10Be (1.6 Ma), 26Al
      (720 ka), 36Cl (301 ka), 41Ca (104 ka), 129I (16 Ma) and other long-lived
      radionuclides occurring in nature at ultra-trace levels. These radionuclides can
      be used as tracers and chronometers in many disciplines: geology, archaeology,
      astrophysics, biomedicine and materials science. Low-level decay counting
      techniques have been developed in the last 40-50 years to detect the
      concentration of cosmogenic, radiogenic and anthropogenic radionuclides in a
      variety of specimens. Radioactivity measurements for long-lived radionuclides are
      made difficult by low counting rates and in some cases the need for complicated
      radiochemistry procedures and efficient detectors of soft beta-particles and low
      energy x-rays. The sensitivity of AMS is unaffected by the half-life of the
      isotope being measured, since the atoms not the radiations that result from their
      decay, are counted directly. Hence, the efficiency of AMS in the detection of
      long-lived radionuclides is 10(6)-10(9) times higher than decay counting and the
      size of the sample required for analysis is reduced accordingly. For example, 14C
      is being analysed in samples containing as little as 20 microg carbon. There is
      also a world-wide effort to use AMS for the analysis of rare nuclides of heavy
      mass, such as actinides, with important applications in safeguards and nuclear
      waste disposal. Finally, AMS microprobes are being developed for the in-situ
      analysis of stable isotopes in geological samples, semiconductors and other
      materials. Unfortunately, the use of AMS is limited by the expensive accelerator
      technology required, but there are several attempts to develop compact AMS
      spectrometers at low (< or = 0.5 MV) terminal voltages. Recent advances in AMS
      will be reviewed with highlights from the scientific programs at Lucas Heights
      and other AMS centres.

PMID- 10879835
TI  - Measurement of 137Cs in dust from steel scrap smelting
AB  - This paper deals with the measurement of 137Cs content in dust produced during
      steel scrap smelting and in the material produced from recycling the dust to
      recover the zinc oxide component. The measured samples have different densities
      and chemical compositions. The addition of radioactive standards to this kind of
      material to prepare a calibration standard is rather difficult. A theoretical
      analysis of the attenuation coefficient for this material together with its
      experimental measurement, show a linear relationship between the coefficient and
      density independent of chemical composition that allows the use of a soil sample
      to prepare calibration standards. An analysis of the validity of the method, as
      well as the development of a density correction factor is detailed. This factor
      is calculated incorporating the linear relationship between attenuation
      coefficient and density to the integral representing detection efficiency, and
      evaluating the integral by means of a Monte-Carlo program.

PMID- 10879836
TI  - Revisiting Currie--how low can you go?
AB  - Over the years many different formulae have been proposed to derive the 'limits
      of detection' for radiometric measurements. With the ever increasing employment
      of quality systems within the radioanalytical laboratory, it is vital that the
      term 'limit of detection' is well understood and defined in the documentation in
      use within the laboratory. This paper reviews the various formulae used to derive
      a limit of detection, most of which claim to be derived from Currie's landmark
      paper of 1968, which set out in detail the means by which the analyst can arrive
      at a limit of detection and limit of determination. However, with the vastly
      increased computing power available to the analyst, coupled with the off-the
      shelf availability of low and zero background detectors, it is now more
      straightforward to arrive at exact solutions to define limits of detection and
      determination. Finally, we set out some examples of decision making at these
      limits and how this may inform the way in which detector time is allocated for
      the measurement of samples containing low levels of radioactivity.

PMID- 10879837
TI  - Accurate computation of coincidence summing corrections in low level gamma-ray
      spectrometry
AB  - The GESPECOR (Germanium Spectrometry Correction factors) software, previously
      developed for computing the self-attenuation and coincidence summing corrections,
      was applied to the computation of the coincidence summing correction factors for
      a well-type and two coaxial HPGe detectors. Cylindrical samples as well as
      Marinelli beaker samples were considered. The computed values are in good
      agreement with carefully measured values. A detailed study of the uncertainties
      assigned to the results was carried out. The analysis shows that the procedures
      used in GESPECOR are reliable and provide results with a well defined accuracy.

PMID- 10879838
TI  - Monte Carlo calculation of the efficiency calibration curve and coincidence
      summing corrections in low-level gamma-ray spectrometry using well-type HPGe
      detectors
AB  - Well-type high-purity germanium (HPGe) detectors are well suited to the analysis
      of small amounts of environmental samples, as they can combine both low
      background and high detection efficiency. A low-background well-type detector is
      installed in the Modane underground Laboratory. In the well geometry, coincidence
      summing effects are high and make the construction of the full energy peak
      efficiency curve a difficult task with an usual calibration standard, especially
      in the high energy range. Using the GEANT code and taking into account a detailed
      description of the detector and the source, efficiency curves have been modelled
      for several filling heights of the vial. With a special routine taking into
      account the decay schemes of the radionuclides, corrections for coincidence
      summing effects that occur when measuring samples containing 238U, 232Th or 134Cs
      have been computed. The results are found to be in good agreement with the
      experimental data. It is shown that triple coincidences effect on counting losses
      accounts for 7-15% of pair coincidences effect in the case of 604 and 796 keV
      lines of 134Cs.

PMID- 10879839
TI  - Determination of thorium in environmental and workplace materials by ICP-MS.
AB  - The paper outlines the advantages of the use of Inductively Coupled Plasma Mass
      Spectrometry (ICP-MS) over radiometric techniques to measure natural thorium,
      232Th. Experimental parameters that must be taken into account in the sample
      digestion, preparation and ICP-MS analysis of environmental (soils, rocks,
      sediments) or workplace (thorium oxide, reference solutions) materials are
      described. The methods presented are applied to various reference materials, with
      the aim of providing suitable procedures to be useful for other important thorium
      containing materials (such as monazite sands or welding electrodes). The
      participation in a European Commission intercomparison exercise is detailed and a
      comparison with alpha spectrometry is made.

PMID- 10879840
TI  - Separation of Tc-99 in soil and plant samples collected around the chernobyl
      reactor using a Tc-selective chromatographic resin and determination of the
      nuclide by ICP-MS
AB  - Technetium (Tc) is known to have high mobility in a soil-water system and also
      high bioavailability for plants, because the most stable form of Tc in natural
      surface environment is thought to be TcO4- which is highly soluble. The chemical
      form of Tc, however, changes with environmental conditions. Thus, it is
      necessary, for realistic assessment, to obtain transfer parameters, such as
      transfer factors, under natural conditions. However, it is difficult to obtain
      these parameters using global fallout 99Tc in actual fields due to its low
      concentration. In this study, 99Tc concentrations in surface soil and plant leaf
      samples collected from forest sites within the 30-km zone around the Chernobyl
      reactor were measured for the first time. In the case of soil samples, a simple
      and rapid analytical method for determination of 99Tc is used which consists of
      volatilizing and trapping Tc in a combustion apparatus, purifying the Tc with an
      extraction chromatographic resin, and measuring it by inductively coupled plasma
      mass spectrometry (ICP-MS). For plant samples, a wet digestion method in
      combination with the resin is applied and the 99Tc is measured by ICP-MS.
      Concentrations of 99Tc in organic soil samples and leaves of strawberry (Fragaria
      vesca) range from 1.1-14.8 Bq kg(-1) dry weight and 0.2-6.0 Bq kg(-1) dry weight,
      respectively. Our results indicate that soil-to-plant transfer factors for Tc are
      similar to those for Cs.

PMID- 10879841
TI  - Measurement of technetium-99 in Marshall Islands soil samples by ICP-MS
AB  - Extraction techniques for recovery of technetium-99 (99Tc) for Inductively
      Coupled Plasma Mass Spectrometry (ICP-MS) measurements were evaluated using soil
      samples collected from the Marshall Islands. The results of three different
      extraction techniques were compared: (MI) acid leaching of Tc from ashed soil;
      (M2) acid leaching of Tc from raw dry soil; and (M3) Tc volatilization from ashed
      soil using a combustion apparatus. Total Tc recoveries varied considerably
      between the extraction techniques but each method yielded similar analytical
      results for 99Tc. Applications of these extraction techniques to a series of
      environmental samples and ICP-MS measurements have yielded first data on the 99Tc
      content of Marshall Islands soil samples contaminated with close-in radioactive
      fallout from nuclear weapons testing. The 99Tc activity concentration in the soil
      samples ranged between 0.1 and 1.1 mBq g(-1) dry weight (dw). The limit of
      detection for 99Tc by ICP-MS was 0.17 mBq per sample or 0.014 mBq g(-1) dw under
      standard operating conditions.

PMID- 10879842
TI  - Accelerator mass spectrometry as a powerful tool for the determination of 129I in
      rainwater
AB  - 129I is a very long-lived radionuclide (T(1/2) = 15.7 x 10(6) years) that is
      present in the environment both because of natural and anthropogenic sources. Its
      environmental interest, for example, as a tracer of geological processes, makes
      it the research target of a growing scientific community. However, its detection
      in environmental samples by radiometric methods is very difficult because of its
      long half-life. In this work, we present the methodology developed for its
      detection by Accelerator Mass Spectrometry (AMS) in rainwater.

PMID- 10879843
TI  - Development of analytical techniques for ultra trace amounts of nuclear materials
      in environmental samples using ICP-MS for safeguards
AB  - The authors have begun to develop analytical techniques for ultra trace amounts
      of nuclear materials and to prepare a clean chemistry laboratory for
      environmental sample analyses. The analytical techniques include bulk and
      particle analyses. For the bulk analysis, concentrations and isotopic ratios of U
      and/or Pu are determined by inductively-coupled plasma mass spectrometry (ICP-MS)
      and thermal ionization mass spectrometry (TIMS). In the particle analysis,
      isotopic ratios of U and/or Pu in each particle will be measured by secondary ion
      mass spectrometry (SIMS). This paper reports on the outline for the development
      of analytical techniques and the current situation of the development of the bulk
      analysis using ICP-MS is described.

PMID- 10879844
TI  - Uranium isotopic data in uraninite spent fuel from the Bangombe natural nuclear
      reactor (Gabon) and its surroundings
AB  - In the framework of the "Oklo-Natural Analogue Phase II" Project, uraninite from
      the Bangombe natural reactor and samples from its host rock were analyzed to
      determine their uranium isotopic composition by thermal ionisation mass
      spectrometry, inductively coupled plasma mass spectrometry and alpha
      spectrometry. There were several objectives for this work: (i) to validate the
      235U/238U isotopic ratios obtained by these techniques; (ii) to test the use of
      the 235U/238U ratio of uraninite as a tracer of migration/retention processes of
      uranium from the source term to the far field; (iii) to evaluate the most recent
      migration/retention processes of uranium in the system by U-series
      disequilibrium.

PMID- 10879845
TI  - Alpha spectrometry sample preparation using selectively adsorbing thin films
AB  - Several years ago, Switzerland introduced limits for natural radionuclides in
      food, e.g. 1 Bq/l for 226Ra or 10 Bq/l for the sum of 238U and 234U in drinking
      water. To make enforcement by regional (cantonal) laboratories more attractive,
      simplified analytical methods had to be offered, at least for drinking water. A
      first step has been the development of radium adsorbing sheets. A 20 mm x 20 mm
      MnO2 film on a polyamide substrate adsorbs more than 80% of the radium present in
      a 100 ml water sample within 6 h. The film is thin enough to allow for high
      resolution alpha spectrometry. A second step now under way is to produce thin
      films, which selectively adsorb uranium. Actually, an ion exchange resin with
      diphosphonic and sulfonic acid groups is used for this purpose. Although not yet
      very thin, these films make possible energy resolutions far better than with any
      liquid scintillation alpha spectrometry method. Adsorption efficiencies are more
      than 80% after 20 h exposition to a 100 ml water sample (20 mm x 20 mm sheet). A
      third step is to have a system that measures radionuclide concentrations in water
      on-line. A prototype is presented where radionuclides are adsorbed on a film in
      contact with the water. A Si-detector placed on the other side of the film
      support counts the alphas passing through.

PMID- 10879846
TI  - Development of a beta-spectrometer using PIPS technology
AB  - Various anthropogenic sources contribute to the inventory of long live beta
      emitters in the environment. Studies have been carried out to obtain the 90Sr
      distribution in environment in order to estimate its impact in terms of radiation
      exposure to humans. The Laboratory routinely measures 90Sr by proportional
      counter after radiochemistry. An incomplete radiochemical separation leads to a
      deposit submitted to count polluted by natural beta-emitters. In order to confirm
      the result, 90Y (daughter of 90Sr), is extracted from the final radiochemical
      fraction and counted. The 90Y decreasing (T(1/2) = 2.67 days) is checked by
      successive counts over 64 h. The delay between the end of radiochemistry and the
      counting is imposed by 15 days to allow radioactive equilibrium between 90Sr and
      90Y to be established. In order to remove this delay the purity of the 90Sr
      fraction source can be verified by beta-spectrometry. Thus, a beta-spectrometer
      is under development in collaboration with Canberra Semi-Conductor and Canberra
      Electronic. It consists in a PIPS detector where several silicon layers are
      combined. Initial results will be presented in this paper.

PMID- 10879847
TI  - On the determination of 226Ra in environmental and geological samples by alpha
      spectrometry using 225Ra as yield tracer
AB  - A method for the determination of 226Ra in environmental and geological samples
      by alpha-spectrometry is described. The method is based on the use of 225Ra, in
      radioactive equilibrium with its parent 229Th, as yield tracer. This tracer
      permits the incorporation of 226Ra determination into the radiochemical procedure
      commonly used for the determination of U and Th isotopes in the same sample.
      Estimation of 225Ra in the alpha-spectra is made via measurement of its alpha
      emitting daughters, 217At being the most suitable to this purpose. In order to
      achieve it, several requirements need to be fulfilled in the radiochemical
      procedure, which will be discussed.

PMID- 10879848
TI  - 210Pb and 210Po determination in environmental samples
AB  - Sequential separation of 210Pb and 21OPo in environmental samples allows the
      determination of these naturally occurring radionuclides with good chemical
      yields and low detection limits. After sample mineralization, part of the
      leaching solution is used for 210Po determination which does not require any
      further treatment and essentially quantitative recoveries are obtained, using a
      standard 209Po tracer. The remaining part of the leaching solution is used for
      210Pb determination. Starting from 3 g sediment (30 l water), the lower limits of
      detection of the method are 1.4 Bq kg(-1) (0.14 mBq l(-1)) for 210Pb and 0.25 Bq
      kg(-1) (0.016 mBq l(-1)) for 21OPo. The procedure has been checked by analysing
      two certified reference materials, supplied by IAEA, and reliable results have
      been obtained.

PMID- 10879849
TI  - Application of a low-background gamma-ray spectrometer to the determination of
      90Sr
AB  - A method for quantitative determination of 90Sr with a germanium gamma-ray
      spectrometer is presented. The bremsstrahlung energy spectrum produced by high
      energy beta particles from the 90Sr source encapsulated in a given absorbing
      material is measured. The idea was tested on various types of low-background
      germanium gamma-ray spectrometers. The optimisation of absorber thickness for
      aluminium, iron, copper, cadmium, tantalum and lead is presented. The lowest
      achieved detection limit for a 10% efficiency HPGe detector was 0.38 Bq/sample
      which allows this method to be applied to some environmental studies.

PMID- 10879850
TI  - Laboratory application of NaI(Tl) gamma-ray spectrometry to studies of natural
      radioactivity in geophysics
AB  - We implemented a laboratory apparatus based on a NaI(TI) gamma-ray spectrometer
      for the assessment of naturally occurring radioactive materials. This apparatus
      is devoted to the quantitative determination of U, Th and K in rock and soil
      samples. We analysed the calibration procedures with particular emphasis to
      factors which affect accuracy and detection limits. A first series of
      measurements were compared to those obtained by means of high energy gamma-ray
      spectrometry. A discussion was made on factors restricting the approach based on
      scintillation spectrometry, such as secular equilibrium and radon encapsulation.

PMID- 10879851
TI  - Determination of radium-226 in environmental and personal monitoring samples.
AB  - Radium-226 is a member of the Uranium-238 natural decay series and is the most
      hazardous radionuclide released to the environment from uranium mining and
      milling. Due to its long half-life (1600 years) and radiological effects it is
      one of the most important isotopes to be determined among the naturally occurring
      nuclides in environmental samples. It is also among the most toxic long-lived
      alpha-emitters present in environmental samples, as well as one of the most
      widespread. The requirement for the determination of radium has become a matter
      of interest in public health due to its hazardous nature with respect to internal
      exposure. It is concentrated in bones, thus increasing the internal radiation
      dose of individuals. The methodology developed involves dissolving solid samples
      by microwave digestion. The radium is then separated from matrix interferents by
      cation exchange chromatography and subsequently electrodeposited onto a stainless
      steel disc. Alpha-Spectrometry is employed to determine the activity in the
      sample. A limit of detection of 20 mBq l(-1) for ground water samples (100 ml)
      and 20 mBq g(-1) for solid samples (0.1 g) is achievable. The method has been
      validated via an intercomparison exercise and analysis of a marine sediment
      reference material. Samples analysed include run off waters from uranium mines,
      coal and fly ash and also trapping media such as silica gel, charcoal and
      activated carbon.

PMID- 10879852
TI  - Rapid 90Sr/90Y determination in water samples using a sequential injection method
AB  - We have developed a semiautomatic procedure based on a sequential injection
      method for 90Sr/90Y determination that allows their radiochemical separation in
      about 30 min. The method has been tested using 90Sr/90Y solutions with activities
      lower than 12 Bq. The source is eluted in a pH = 6.5 medium through a MnO2
      impregnated cotton filter, where 9OY is preconcentrated in preference by
      adsorption. 90Y is extracted from the column with hydroxylamine, some 90Sr in the
      leached solution has also been found. After the radiochemical separation, the
      total beta-activity of the leached solution has been determined using a low
      background alpha-beta proportional counter and, assuming the presence of 90Sr and
      90Y at t = 0, the solution of the Bateman equations allows the initial
      concentration of both isotopes to be obtained. We have verified that the addition
      of some ions usually found in water samples (Cl-, HCO3-, NO3-, SO4(2-), Ca2+,
      Mg2+) does not interfere with the yield of the radiochemical process, (90 +/-
      10)%. The method has been applied to 90Sr/90Y determination in mineral waters,
      and even in thermal waters, where the salt concentration can be about 3500 mg/l,
      the radiochemical yield remains greater than 80%.

PMID- 10879853
TI  - Improvement in 90Sr measurements at very low levels in environmental samples
AB  - Various anthropogenic sources contribute to the inventory of long lived beta
      emitters in the environment. Studies have been carried out to obtain the 90Sr
      distribution in environment in order to estimate its impact in terms of radiation
      exposure to humans. Various environmental samples were collected and analysed for
      90Sr activity concentrations. As natural beta emitters are present in all
      matrices, an incomplete radiochemical separation leads to over evaluation of the
      results. An accurate and reliable method has been routinely implemented to
      extract, purify, and analyse 90Sr in all types of environmental matrices by the
      Laboratory of Radioactive Measurement in Environment. The radiochemical procedure
      is combined with a proportional counting for 90Sr detection. After leaching the
      20 g aliquot, different protocols have been tested. The effectiveness of Sr-spec
      resin for Sr isolation has been demonstrated and chosen for the protocol
      selected. Radiochemical procedure was tested using IAEA reference materials.
      Results are discussed in terms of recovery, purification efficiency and limit of
      detection. The influence of a filtrated atmosphere on proportional counting is
      also discussed.

PMID- 10879854
TI  - In situ sorption of technetium using activated carbon
AB  - The sorption of technetium in pertechnetate form on carbon has been investigated.
      The sorption is pH dependent with maximal distribution coefficients, Kd, in the
      order of 10(6) at pH 2-4 for activated carbon with a grain size < or = 100
      microm. The equilibrium time to reach such distribution coefficient was about 5 h
      at room temperature. The exact mechanisms for the sorption are not fully
      understood but reduction of Tc by the carbon might be an important process.
      Technetium can effectively and rapidly (5 l min(-1)) be sorbed from very large
      volumes (several hundred liters) of environmental waters on commercial cartridge
      filters impregnated with activated carbon. After incineration, the filters can be
      analyzed for 99Tc by conventional methods.

PMID- 10879855
TI  - Low level 137Cs measurements in deep seawater samples
AB  - The ammonium phosphomolybdate (AMP) procedure for low level 137Cs measurements in
      deep seawater samples was examined, as a marked decrease in the recovery of AMP
      has been observed over several years. An improved AMP procedure is proposed:
      adjust the pH to 1.6-2.0, next add 0.26 g CsCl to form an insoluble compound,
      then add 4 g AMP to every 20-100 l seawater sample. Stir at a rate of 25 l
      air/min for 1 h, then recover the AMP/Cs compound after 6-24 h. The weight yield
      of AMP/Cs compound was about 98% of AMP for 20 l samples and the radiochemical
      137Cs yield was 96-100%. The absolute efficiency of the HPGe coaxial well
      detector was 16% for 137Cs at 662 keV for 4 g AMP/Cs compound. Using the improved
      procedure, 137Cs activities in 20-100 l samples from sea surface to near bottom
      in the western North Pacific were measured. The 137Cs concentrations in deep
      water samples were lower than 0.1 Bq m(-3) in 1997 and 1998. This procedure
      allows a wide range of applications of 137Cs as a transient tracer for
      oceanographic purposes, as high resolution water profiles are obtained due to the
      smaller volume of samples needed.

PMID- 10879856
TI  - The development of a sequential method for the determination of actinides and
      90Sr in power station effluent using extraction chromatography
AB  - Determination of the actinides and 90Sr in power station effluent requires their
      radiochemical isolation prior, to measurement. Historically, techniques such as
      precipitation, ion exchange and solvent extraction have been used but these
      methods can be complex, time consuming and produce large amounts of chemical
      waste. A more environmental friendly sequential scheme for their determination in
      power station effluent using extraction chromatography has been developed. This
      is a simplified method which minimises chemical waste and makes use of
      commercially available pre-packed chromatography columns. An Eichrom TRU.Spec
      column was used for the separation of isotopes of plutonium from americium and
      curium followed in sequence by an Eichrom Sr.Spec column for the separation of
      90Sr. The isolated actinides were prepared for alpha spectrometry analysis by
      electrodeposition and 90Sr was analysed by liquid-scintillation counting. The
      tracers 242Pu, 243Am and 85Sr were used to measure chemical yields. Method
      evaluation was carried out on water samples spiked with certified radionuclide
      standards to determine precision, accuracy, detection limits and chemical
      recoveries. Finally, testing and evaluation of the method was carried out on
      power station effluent.

PMID- 10879857
TI  - The PTB underground laboratory for dosimetry and spectrometry
AB  - In 1991, the Physikalisch-Technische Bundesanstalt established an underground
      laboratory for dosimetry and spectrometry (UDO) at the Asse salt mine, near
      Braunschweig. Due to the depth of 925 m below ground (equivalent to about 2100 m
      of water), the cosmic ray muon intensity in this facility is reduced by more than
      5 orders of magnitude. In addition, the low specific activity of the pure rock
      salt and a low concentration of radon lead to an extremely low ambient dose
      equivalent rate of less than 1 nSv/h. The UDO facility is therefore well suited
      for dosimetry at very low dose rates, as well as for Ultra-Low-Background (ULB)
      gamma-ray spectrometry. In 1998, a coaxial low-background HPGe-detector (88%
      relative efficiency, FWHM 2.0 keV at 1.33 MeV) with an extended shielding (20 cm
      low-activity lead, 1 cm electrolytic copper, N2-flushing) was installed at UDO;
      the count rate per mass of germanium, integrated over the energy range from 40 to
      2750 keV, was measured to be 0.012 s(-1) kg(-1). Results from test measurements
      and first applications are reported. The design of a ULB gamma-detector system,
      presently under construction, is described.

PMID- 10879858
TI  - Radioactivity measurements for the thin layer activation technique
AB  - Thin layer activation (TLA) is one of the promising techniques employing
      radiotracers at low levels of radioactivity for material performance studies such
      as wear and corrosion. The principle of TLA is the creation of an appropriate
      radionuclide in a given material to a well defined depth of a selected area. This
      activation is realised by exposure of the component to a charged particle beam
      using, e.g., a cyclotron facility. If the material is subjected to mechanical or
      chemical degradation, any loss of the activated material will result in a loss in
      radioactivity of the activated component. The sensitivity of TLA technique is
      high due to the capability of low level radioactivify measurement performed by
      gamma spectrometry. The sensitivity of TLA is below 0.1 microm thickness loss or
      1 ng mass loss. In the present paper, some applications of TLA in ongoing
      research at the Institute for Health and Consumer Protection of the European
      Commission are presented.

PMID- 10879859
TI  - A Monte Carlo simulation of background characteristics of low-level HPGe
      detectors
AB  - The radionuclide levels observed at present in the marine environment are very
      low, therefore high sensitive spectrometric systems are required for carrying out
      oceanographic investigations. The present-state-of-the-art carefully designed low
      level HPGe gamma-spectrometers, which do not operate underground, have a
      dominating background component induced by cosmic rays, mostly by cosmic muons.
      High energy cosmic rays can initiate a large number of physical processes leading
      to background induction. Analytic solutions for describing these processes are
      not available and therefore, a Monte Carlo simulation is necessary. The
      development of a simulation code for background induction is useful for the
      optimisation of a counting system in respect to its background characteristics.
      It enables to assert the background before the system is built and also to
      perform systematic investigation of the influence of various parameters on the
      background of the detector. The GEANT code has been selected from the codes
      systems facilitating the simulation of the passage of particles through matter,
      as it best meets the requirements for simulations with high-energy muons. The
      obtained results show that the background depends most significantly on the
      thickness, the size and lining of the shield. Lead shielding of 15 cm thick has
      been found to be the optimum shielding for most applications. It is not advisable
      to build an unnecessarily large shield. A shield with removable lining would be
      the best as the lining can be removed from applications where the lead X-rays are
      not a disturbing influence.

PMID- 10879860
TI  - Low level gamma-ray germanium-spectrometer to measure very low primordial
      radionuclide concentrations
AB  - A new germanium spectrometer especially suited for large sample measurements is
      described in detail. It is operated in the Gran Sasso underground laboratory
      under shielding rock of 3300 m water equivalent, which reduces the muon flux by
      six orders of magnitude. The integral background counting rate in the energy
      range from 50 to 2750 keV is about 0.15 min(-1). The low peak count rates of
      mostly less than 1 count per day together with a relative efficiency of 102% and
      the high sample capacity makes this spectrometer one of the most sensitive
      worldwide. Some sample measurements for the solar neutrino experiment BOREXINO
      and the detector efficiency calibration by the Monte Carlo method are discussed
      as well.

PMID- 10879861
TI  - Determination of Zn in high-purity GaAs with neutron activation analysis
AB  - Neutron activation analysis was used to analyse Zn concentrations in high-purity
      GaAs. A combination of chemical separation of the neutron-induced 65Zn from the
      GaAs-matrix with anion-exchange chromatography and ultra low-level gamma-ray
      spectrometry in an underground laboratory was applied. Zn concentration ranged
      from 2.1 to 51 ng g(-1), and detection limits from 0.018 to 0.059 ng g(-1) were
      obtained.

PMID- 10879862
TI  - Investigation of the soil-plant transfer of primordial radionuclides in tomatoes
      by low-level gamma-ray spectrometry.
AB  - The paper presents actual data from investigations of the soil-plant transfer of
      the primordial radionuclides 40K, 238U, 226Ra, 210Pb and 227Ac for tomatoes
      growing at soils from former uranium mining areas. The analysis were carried out
      using low-level gamma-ray spectrometry in a 47 m deep underground laboratory. For
      tomato fruits transfer factors of (0.0007 +/- 0.0006) for 235U, (0.0021 +/-
      0.0017) for 226Ra, (0.0015 +/- 0.0009) for 210Pb and (0.0018 +/- 0.0012) for
      227Ac were obtained. The investigation of the soil-plant transfer by low-level
      gamma-ray spectrometry is often limited by the Compton-continuum from the always
      present high-energy gamma-ray emitter 40K.

PMID- 10879863
TI  - Determination of 75Se, 95Zr, 237Np and 241Am activities in Boom Clay samples from
      laboratory migration experiments using gamma-ray spectrometry
AB  - Percolation tests (i.e. routine laboratory migration experiments) have been
      performed to evaluate the diffusion behaviour of a number of long-lived
      radionuclides in Boom Clay, a candidate geological host formation for high level
      radioactive waste (HLW) in Belgium. Among the many potentially hazardous
      radionuclides under investigation are 79Se, 93Zr, 237Np, 241Am and 243Am.
      Actinide migration experiments have been carried out with 237Np and 241Am, while
      for the studies with Se and Zr the radioisotopes 75Se and 95Zr were used. Their
      transport patterns in the Boom Clay were examined using a combination of a
      NaI(Tl) detector and High-Purity Ge detectors either on the dissolved matrix
      (237Np, 241Am) or directly on the clay (75Se, 95Zr).

PMID- 10879864
TI  - Practical applicability of field gamma-ray scintillation spectrometry in
      geophysical surveys
AB  - We discuss the problems and calibration procedures for a portable gamma-ray
      scintillation spectrometer for determinations of potassium, uranium and thorium
      concentration in rocks. Particular emphasis was given to the evaluation of the
      background radiation. The apparatus was tested in the field at two selected areas
      in NW Italy. We found appropriate sites which could be used as reference targets
      to frequently check the gamma-ray equipment. An area formed by serpentinitic
      rocks showed such a low measured radioactivity that it could be used as a
      reference for the local background effect. An anomalously high uranium amount
      against negligible potassium and thorium concentrations were found in outcrops of
      dolomitic rocks, which can be used to detect possible changes in the instrument
      calibration constants.

PMID- 10879865
TI  - Low level gamma spectrometry by beta-gamma coincidence
AB  - A beta-gamma coincidence system consisting of a 2pi plastic beta detector and a
      Ge(Li) detector, is described. Such a system allows for a drastic reduction of
      background (approximately 70 times) as well as of Minimum Detectable Activity
      (approximately 7 times). An integral background (50-1500 keV) of less than 0.1
      cps is obtained. The difficulty of the method, otherwise simple and inexpensive,
      is the precise determination of beta detector efficiency.

PMID- 10879866
TI  - Recent developments in ultra low-level gamma-ray spectrometry at IRMM
AB  - IRMM performs ultra low-level gamma-ray spectrometry in the underground
      laboratory HADES, located at the SCK-CEN site in Mol, Belgium. Recently a third
      low-background coaxial HPGe detector was put into operation. The detector has 60%
      relative efficiency and better background characteristics than the two previous
      detectors: The shield comprises 14 cm of lead with 21OPb specific activity of 20
      Bq kg(-1) and 14 cm of freshly produced electrolytic copper. The background count
      rate integrated from 40 to 2700 keV is 394 +/- 2 counts per day. Details of the
      background and the shield are presented together with applications to nuclear
      safeguards and material selection.

PMID- 10879867
TI  - Anticompton spectrometer element studies
AB  - Sensitive measurements of the trace elements require the use of an active
      suppression of the overall detection background. For this reason, an anticompton
      system made of NaI and HPGe has been constructed at the new underground
      laboratory in Garching near Munich for analysis of irradiated samples.
      Significantly improved limits for trace elements' concentration in nylon have
      been obtained. A suppression factor of 16 in the energy region of 100-400 keV was
      reached.

PMID- 10879868
TI  - Quality assurance of automated gamma-ray spectrometric analysis
AB  - Fully automatic gamma-ray spectrometric analysis procedures perform complete
      processing of the spectrum without intervention of the operator. In order to
      maintain the reliability of the final results the analysis checks the
      intermediate results automatically. When a disagreement is identified by such a
      check the uncertainty of the intermediate results is increased in order to
      accommodate the disagreement. The increased uncertainty is propagated into the
      uncertainty of the final results in order to take into account the disagreement.
      This approach was implemented in Canberra's Genie ESP gamma-ray spectrometry
      package for examining the results of the peak analysis. In addition to this
      intermediate check also a-posteriori checks of the final results can be performed
      by statistical analysis. Such analysis shows whether the results are under
      statistical control and can discover sources of variability which are not taken
      into account in the uncertainty budget.

PMID- 10879869
TI  - The standardisation of 229Th for an environmental yield tracer
AB  - The naturally occurring long-lived nuclides of thorium (228Th, 230Th and 232Th)
      are all alpha-emitters that are of interest both to the nuclear and non-nuclear
      industries and levels of these nuclides need to be monitored in both the working
      and natural environment. In order to do this in a manner where the results of
      radiochemical analysis are traceable to national standards, a chemical yield
      tracer has to be employed. 229Th has been identified as a suitable tracer for
      such purposes and has been used in the past. This paper describes the absolute
      standardisation of 225Th by 47pi alpha-gamma coincidence counting. The results of
      this work are presented together with an analysis of the standardisation
      uncertainties that were achieved in practice.

PMID- 10879870
TI  - Plutonium and other alpha-emitters in bones of wild, herbivorous animals from
      north-eastern Poland.
AB  - The results of the investigation of (239+240)Pu, 241Am and thorium isotope
      activity concentrations in bones of wild herbivorous animals (deer, roe-deer,
      boars, elks) from north-eastern Poland are presented. The area on which the
      animals were living had relatively high Chernobyl plutonium fallout. Possible
      traces of plutonium were seen only in four samples, but only for one it was it
      3sigma above background, at 6.2 +/- 2.4 mBq/kg (ash). The 241Am activity
      concentration was below the detection limits in all samples. The maximum 228Th
      concentration in the samples was 7.81 +/- 0.44 Bq/kg (ash), calculated under the
      assumption of 100% thorium recovery. This isotope seems to originate in bones not
      from direct incorporation but from the decay of 228Ra. Large variations in
      activity concentration wose observed, as well as some differences between boars
      and the chewing animals.

PMID- 10879871
TI  - Analysis of plutonium in soil samples
AB  - Procedures for analysis of plutonium in soil samples were developed using anion
      exchange as a purification technique. Special attention was paid to removing
      impurities of 228Th which interferes in 238Pu determination by alpha
      spectrometry. Two anion-exchange methods were compared. The determination of
      plutonium in soil involves the conversion of soil samples to acid-soluble form.
      Two methods for the extraction of plutonium from a natural reference soil were
      compared. The first method (a direct digestion in nitric acid) is suitable for
      the determination of plutonium in large amounts of sample. The second method
      involves microwave digestion of soil (5 g) with a mixture of HNO3, HCl and HF,
      and is suitable for saving time in routine determinations. Activities calculated
      with a reference soil matrix were in good agreement with the reference value. The
      microwave digestion method was applied in a study of different soil samples, and
      recoveries ranged between 20% and 50%.

PMID- 10879872
TI  - Thorium in the workplace measurement intercomparison.
AB  - The monitoring of radionuclides in the nuclear industry has been recognized as
      the most straightforward way of assessing health and safety issues associated
      with the exposure of the workforce to potentially harmful radiation doses. Much
      of this is achieved by measurements in the workplace itself and by the bioassay
      and monitoring of workers in the industry. However, there also exists a
      significant 'non-nuclear' industry where workers are exposed to radioactive
      materials, for example where this involves thorium, which is made wide use of in
      the aerospace and other high technology industries. As such work involves the
      processing of thorium bearing materials, the workforce is potentially exposed to
      232Th and its daughter nuclides. Thus, to monitor the workforce effectively, it
      is important to be able to measure both 232Th and the decay products of 232Th
      where they are in an unknown state of radioactive equilibrium and this is where
      monitoring laboratories may experience some difficulty. Accordingly, the Health
      and Safety Laboratory in the UK has organized a EC wide project on the monitoring
      of thorium in the 'non-nuclear' workplace; this project is currently ongoing. We
      report the results of the first intercomparison of this project involving two
      solutions of 232Th, one in radioactive equilibrium and one not in equilibrium
      with its daughters. The results are presented with some comments on how this
      intercomparison has progressed and how these first results will inform the rest
      of the project.

PMID- 10879873
TI  - Actinoid separations by extraction chromatography
AB  - Two separation methods based on extraction chromatography are presented: the
      first for the determination of Pu and Am, and the second for U and Th. These two
      methods are applied to (i) the determination of Pu and Am in diluted MOX samples
      and (ii) the analyses of Th from four standard solutions. Both of the methods
      gave high recoveries and showed good reproducibility for Th, Pu and Am. Special
      requirements for the determination of Th are discussed.

PMID- 10879874
TI  - Pre-concentration of actinoids from waters: a comparison of various sorbents
AB  - The first part of comparison study was based on the properties of different
      sorbents. These included different forms of manganese oxides, and specific
      organic ion-exchangers: HYPHAN and POLYORGS. In order to provide reproducible
      samples with moderate presence of possible interferences, spiked tap water was
      used for this first set of experiments. Results indicate that the sorption of Th,
      U, Pu and Am varies for different forms of manganese oxides. These variations are
      attributed to different physico-chemical properties of the oxides. HYPHAN was
      limited in its sorption to Th and U. The manganese oxide dissolved rapidly and
      the radiochemical separation procedure was quick and simple using extraction
      chromatography techniques. The radionuclides in the water samples were determined
      by ICP-MS and/or alpha spectrometry.

PMID- 10879875
TI  - A multiple window deconvolution technique for measuring low-energy beta activity
      in samples contaminated with high-energy beta impurities using liquid
      scintillation spectrometry
AB  - An optimised multiple window counting technique, using liquid scintillation
      counting combined with internal standardisation and spectrum unfolding has been
      developed for the assessment of low-level, low-energy beta activity in
      multilabeled samples containing high-energy beta impurities. Distinct spectral
      contributions are reconstructed for every individual radionuclide and impurity
      using software deconvolution techniques. The most important advantages of this
      method are that it does not require setting up quench correction curves and that
      the exact knowledge of reference activity is not required, thus eliminating two
      important sources of uncertainty in the final results. The technique has been
      successfully used on mixtures of 3H, 14C, 63Ni, 99Tc and 60Co over a wide range
      of quenching and activity ratios.

PMID- 10879876
TI  - A multi-sample liquid scintillation counting system for weak beta-emitting
      samples with single phototube detectors
AB  - The relative merits of low-level liquid scintillation counters with one and two
      phototubes, respectively, are discussed and an analysis of their background
      components is presented. A simple and compact system with manual sample changing
      is described. It counts four samples simultaneously, and it is based on the
      single-phototube arrangement where conical vials sit on the top of 28 mm diameter
      phototubes. A PC computer collects and processes the pulses from a specially
      designed electronic unit. The system is operated in a small underground counting
      room, a closet in the wall of a road tunnel under a fjord. Its performance is
      described.

PMID- 10879877
TI  - Liquid scintillation determination of low level components in complex mixtures of
      radionuclides
AB  - A new approach to simultaneous activity measurements of the complex radionuclide
      mixtures using liquid scintillation counting, which is applicable to the analysis
      of the environmental and technological samples, is presented. The method is based
      on specially developed software 'SpectraDec', realized on a Windows 95/98/NT
      platform and a spectra library created for different kinds and levels of
      quenching. The method allows analysis of complex mixtures when the activity
      ratios of the individual components vary considerably. For example, the
      radionuclide concentrations were successfully determined in the following complex
      mixture: 3H, 63Ni, 90Sr + 90Y, 137Cs, 241Am (model mixture), where the 90Sr +
      90Y/3H activity ratio was 1/2500 (0.2 Bq/500 Bq) and 90Sr, 137Cs, 134Cs, 232Th,
      226Ra (IAEA-reference sample), where the 90Sr/137Cs activity ratio was 1/50 (92
      Bq/4515 Bq) with an accuracy of about 20%. The limitations of the given approach
      to the LS analysis of the radionuclide mixtures are considered.

PMID- 10879878
TI  - On low-level tritium measurements with LSC Quantulus
AB  - Low-level measurements of 3H have been made with the "Quantulus" liquid
      scintillation counter (LSC) using different scintillation cocktails together with
      selected types of counting vials. Comparisons were made between counters at the
      underground laboratory "Felsenkeller" (110 m water equivalent) and in an above
      ground laboratory (0 m water equivalent) of the TU Freiberg. In the underground
      laboratory, the background is strongly influenced by the beta-decay of the 220Rn
      daughter 212Pb (T(1/2) = 10.6 h) from the laboratory air, stimulating
      luminescence irradiation in the vial. The effective background count rate in the
      3H-window (having subtracted the "luminescence effect") in the underground
      laboratory is two times lower than that in the above ground laboratory due to the
      better shielding of cosmic rays.

PMID- 10879879
TI  - Non-destructive assay methods for the free release of dismantling wastes
AB  - The determination of isotope specific activities, and above all, the
      identification of radioisotopes is an important issue in the waste management of
      nuclear wastes whatever their origin. Systems based on the detection of the gamma
      rays emitted by the radionuclides allow the non-destructive assay (NDA) of
      relatively large volumes of waste. Different NDA systems are commercially
      available for this purpose. NDA of waste items is subject to the influence of
      many different physico-chemical characteristics of the sample, most of which are
      generally not known. In many cases, however, NDA is the only approach that allows
      measuring these large samples. The unconditional free release of wastes
      originating from nuclear activities for a great deal relies on NDA systems and
      procedures for decision-making on free release. The assay of waste of very low
      activity and even the decision if a radionuclide has been detected or not, is
      very often difficult. The poor measurement precision, caused by the bad counting
      statistics, combined with a generally unknown bias of the measurement complicate
      the interpretation of the results, and accurate measurements are seldom obtained
      in these cases. The aim of the present paper is to give an overview of the
      efforts made at SCK-CEN to come to a consistent system that allows performing
      free release measurements, involving a high throughput of large amount of
      materials, as expected from a dismantling project.

PMID- 10879880
TI  - The free release of dismantled materials. The practical case of the BR3 reactor
AB  - The dismantling of a nuclear power reactor produces a large quantity and variety
      of obsolete materials. Besides the activated materials which must be evacuated as
      radioactive waste, a large quantity of materials can either be recycled in the
      nuclear sector or free released as non-radioactive materials. Dismantling is a
      complex task so that to achieve our main goal of minimisation of radioactive
      waste production, it requires the set-up of procedures and free release criteria,
      a strict follow-up and a traceability at all steps. The free release of obsolete
      materials can be achieved by several processes such as, melting in a nuclear
      foundry, or by various physical and chemical decontamination processes. The final
      key point is the measurement of a very low level radioactivity for large items or
      for a high throughput.

PMID- 10879881
TI  - Release measurements for materials out of controlled areas
AB  - Large amounts of dismantled materials from nuclear power plants show such a weak
      level of radioactivity that they could be released after decision measurements.
      Till some years ago, the decision measurements taken for the release were based
      only on determining the mass-specific activity of samples by means of gamma
      spectrometry and/or manual sequential measurements of the surface activity with
      large area gas flow counters. The choice of an appropriate measuring method, the
      layout of the release measurement facility (RMF), the way of preparing the
      material and the development of smart release procedures are very important for a
      large throughput and an economic performance of the release process. NIS and
      RADOS have developed RMF based on gross gamma activity. The NIS-RMFs have been
      applied for the last 10 years for decision measurements in different operated but
      also in dismantled nuclear power plants. Together with RMFs from RADOS, more than
      12,000 Mg of various types of materials have been measured up to now with this
      method in Germany.

PMID- 10879882
TI  - Radiological characterization of a uranium mine with no mining activity
AB  - We report a radiological study of a uranium mine located in Extremadura, in the
      south-west of Spain, in which mining work had ceased. One interest in the work is
      that the results can be used as a reference for the future evaluation of the
      effects produced by the restoration program. The radiological parameters selected
      to estimate the impact of the inactive mine were: 222Rn in air and water, 222Rn
      exhalation, effective 226Ra in soils and sediments, and natural uranium and 226Ra
      in water. Chemical analyses of water samples and measurements of meteorological
      variables were also made. Average values of these radiological parameters are
      presented. We characterize the zone radiologically and estimate the influence of
      the mine on the basis of some of these parameters, while others are used to
      reflect the status of the installation, information which could be very useful in
      the near future when restoration is complete.

PMID- 10879883
TI  - Indirect monitoring of internal exposure in the decommissioning of a nuclear
      power plant in Spain.
AB  - The experimental procedure used for the indirect measurement of internal exposure
      of workers involved in the first step of the decontamination of a nuclear power
      plant which is being decommissioned is presented. The establishment of
      decontamination and decommissioning programs is currently in progress at the
      nuclear power plant and monitoring procedures to assess workers' exposure have
      also been implemented. Due to the presence of transuranics, the monitoring
      program includes the analysis of excreta samples. An analytical method for the
      determination of plutonium (Pu) and americum (Am) in urine samples was developed.
      The radiochemical separation is based on the coprecipitation of transuranics and
      sequential isolation of Pu and Am by anion exchange and extraction
      chromatography. Finally, electrodeposited sources are prepared and counted by
      alpha-spectrometry.

PMID- 10879884
TI  - Experience with checking potentially contaminated materials released to the
      environment and testing of the measuring instruments used
AB  - Several systems with large area plastic scintillators were tested, which are used
      to avoid the undesirable and illegal transport of radioactive materials
      especially at border crossings, in metallurgical works and in plants processing
      metal scrap, were tested. Measuring equipment with germanium detectors, which is
      used for check of material released from the Dukovany Nuclear Power Plant, was
      also tested. The detection possibilities of a chamber with plastic scintillators,
      for the use during checking of materials released to the environment, were
      investigated.

PMID- 10879885
TI  - Uranium determination in samples from decommissioning of nuclear facilities
      related to the first stage of the nuclear fuel cycle
AB  - Large amounts of waste materials are generated during the decommissioning of
      nuclear facilities. Clearance levels are established by regulatory authorities
      and are normally quite low. Determination of those activity concentration levels
      becomes more difficult when it is necessary to quantify alpha emitters such as
      uranium, especially when complex matrixes are involved. In addition, an adequate
      workplace monitoring must be carried out during the decommissioning activities,
      to ensure the protection of workers involved in these tasks. Several methods for
      uranium determination in samples obtained during the decommissioning of a
      facility related to the first stage of the nuclear fuel cycle are presented in
      this work. According to the kind and sample size, together with the minimum
      detectable activity (MDA) that must be reached in each case, measurements were
      carried out by laboratory and 'in situ' gamma spectrometry, as well as by alpha
      spectrometry. A comparison among the different techniques was also performed by
      analysing the results obtained in some practical applications.

PMID- 10879886
TI  - Retrospective radon assessment by means of 210Po activity measurements.
AB  - A method for retrospectively assessing the average radon concentration in a
      dwelling, for a period as long as 40 years or more, is described. It is based on
      the free penetration of radon gas into bulky spongy materials called volume
      traps, and subsequent trapping of radon decay products inside them. This leads to
      a build-up of 210Pb, a radon decay product with a half life of 22.3 years, which
      reaches an equilibrium with the alpha emitter 210Po, indicative of the average
      radon concentration over the exposure period. The stuffing of mattresses, chairs,
      cushions, etc. can be considered a good volume trap. A chemical separation
      procedure is described, transforming the volume trap into a 210Po alpha source,
      whose activity is determined through alpha spectroscopy. The technique has been
      applied in over 300 samples, retrieved from dwellings in Serbia, Germany, Norway
      and Sweden. The technique has proven to be very robust and reproducible. In cases
      where radon data were available during the exposure period of the volume trap, a
      remarkable agreement was found. The best volume traps appeared to be polyester
      sponges found in many stuffings. The major drawback is the destructive nature of
      the method, its major advantage is the direct relationship between the radon gas
      and the 210Po signal. The technique can be useful in epidemiological studies of
      the lung cancer risk from indoor radon, for assessing the long term radon
      exposure.

PMID- 10879887
TI  - A compact multiparameter acquisition system for radon concentration studies
AB  - A compact device suitable to acquire and display, at the same time, radon
      concentrations in a given atmosphere, and the environmental parameters
      characterising the atmosphere, is presented and described. It consists of two
      main blocks: (i) a detection section including a set of sensors for measuring
      pressure, humidity and temperature, and a set of silicon surface barrier
      detectors mounted in electrostatic cells collecting the ionised radon daughters;
      (ii) a single NIM module featuring an eight channel 12 bit ADC and the linear
      electronics to shape the signals from the silicon detectors. The system is
      controlled by a computer via a RS232 port. The software, implemented in Visual
      Basic, allows to display the energy distribution of the pulses coming from the
      alpha detectors and to initialise and control all phases of the acquisition. The
      results of preliminary tests show the high reliability of the system.

PMID- 10879888
TI  - 222Rn emanation measurements at extremely low activities
AB  - For the solar neutrino experiment Borexino, a system has been set up to measure
      emanation of 222Rn in samples of up to 80 litres volume. The apparatus has been
      constructed to high vacuum standard and consists mainly of parts made from
      electropolished stainless steel. The low blank activity of the system together
      with a highly sensitive detection method for the extracted Rn leads to a
      sensitivity level in the range 70-100 microBq 222Rn. Due to the large sample
      capacity of the emanation chambers, it is possible to measure specific emanation
      rates as low as several microBq/m2. Some measurements characterizing the
      performance of the apparatus are discussed.

PMID- 10879889
TI  - A compact automatic low-level liquid scintillation system for radon-in water
      measurement by pulse pair counting
AB  - A novel compact liquid scintillation counting system with automatic changing of
      seven samples, dedicated to the assay of low levels of 222Rn in water, is
      described. Its has a single phototube, and its operating mode is 222Rn series
      selective, as only the close pulse pairs given by 214Bi and its short lived decay
      product 214Po (half life 0.16 ms), are counted. Its 214Bi/214Po counting
      efficiency is 90.4% and the background, with an unshielded detector, is 3 pulse
      pairs per hour. 75% of the radon in 200 ml water samples is transferred to the
      scintillator (15 ml toluene) by circulating air, which is bubbled through the two
      liquids for 4 min. With a counting time of 3 h, the minimum detection level is 8
      mBq l(-1). The method is also suitable for various environmental and geophysical
      studies of 222Rn and 226Ra.

PMID- 10879890
TI  - New purification protocol for actinide measurement in excreta based on calixarene
      chemistry.
AB  - The determination of actinides concentration level in excreta, mainly urine is
      currently carried out to monitor people potentially exposed to alpha emitters. To
      measure actinides in such samples, specific analytical protocols have been set
      up. The chemical purification uses different chromatographic columns to
      selectively separate the actinides and each fraction, after electroplating, is
      measured by alpha spectrometry. To reach 1 mBq l(-1) of U, Pu or Am using these
      protocols, 6 days equally distributed between the chemical purification and the
      measurement are necessary. The protocol proposed here is based on a single
      extractant, the 1,3,5-trimethoxy-2,4,6-tricarboxy-p-tert-butylcalix[6]arene, used
      to selectively separate U, Pu and Am from the urinary matrix prior to be
      measured. Using this analytical protocol, U and Pu are quantitatively and
      selectively recovered in two different acidic backextraction solutions whereas Am
      is quantitatively and selectively recovered in the organic phase. Furthermore,
      the purification stage is considerably shortened. The uranium and plutonium
      amounts are measured in aqueous phases using alpha spectrometry or inductively
      coupled plasma-mass spectrometry, whereas Am is measured in the organic phase
      using alpha liquid scintillation (photon/electron-rejecting alpha liquid
      scintillation).

PMID- 10879891
TI  - Development and characterisation of a head calibration phantom for in vivo
      measurements of actinides.
AB  - The investigation of actinides' internal contamination in human body makes use of
      a variety of techniques. In large scale screening the technique of "in vivo"
      evaluation of bone 241Am burden via the determination of the nuclide activity in
      the skull is often used. For this purpose, adequate calibration procedures and
      standard phantoms are needed. The present paper summarises the studies and
      technical procedures followed for the development of a calibration phantom based
      on a commercial Alderson angiographic head in which a set of 24 241Am point
      sources were embedded. A theoretical study was first carried out, at the ENEA
      Institute for Radiation Protection, using the MCNP4-B Monte Carlo code to
      determine the point source distribution that closely approximates a homogeneous
      bone contamination. The numerical models were also used to evaluate the resulting
      degree of approximation. The point sources were prepared at the ENEA National
      Metrology Institute for ionising radiation quantities and were traceable to the
      Italian national standard of radionuclide activity. The sources were prepared by
      quantitatively dispensing a liquid solution onto a plastic disc. The activity of
      each source was checked by gamma-ray spectrometry and the reproducibility of the
      activity values was determined. Each source was then placed in the optimum
      position in the skull, given by the Monte Carlo modelling, by a precision
      mechanical device. The phantom was finally used to calibrate a whole body counter
      operating at the ENEA Institute for Radiation Protection. The paper reports the
      main theoretical and experimental aspects of this work, and also discusses the
      results of the first calibrations.

PMID- 10879892
TI  - Training of medical students and nurses to be members of cancer care teams.
AB  - BACKGROUND: A multiprofessional approach to the treatment of cancer patients
      already exists. However, in the educational process the principle of training
      students to work in cancer care teams is not yet common. Since 1998,
      undergraduate students in university schools of nursing in Ukraine have been
      studying oncology as a separate subject. Because nursing students are trained in
      oncology departments of medical universities, it is possible to teach a team
      approach to medical and nursing students simultaneously. Thus, a unified training
      program in oncology was initiated. METHOD: The keystone of this approach is the
      training of medical and nursing students to function as a cancer care team.
      RESULTS: The project is still at an early stage of development. The team is
      envisioned to consist of a physician-nurse student working unit. The theoretical
      knowledge of medical and nursing students and their practical skills should
      complement each other in each department in a comprehensive cancer hospital.
      CONCLUSIONS: This teaching method should foster a professional relationship
      between the doctor and the nurse and contribute to their mastering cancer
      knowledge, which in practice will enable them to work as a team. Teaching
      students to function as cancer care teams should be considered for primary
      clinical training in oncology for future physicians and nurses.

PMID- 10879893
TI  - Cancer Prevention and Control Training Program at the University of Alabama at
      Birmingham.
AB  - The pre- and postdoctoral Cancer Prevention and Control Training Program (CPCTP)
      at the University of Alabama at Birmingham (UAB) has attracted high-quality
      trainees from all over the United States. The trainees have pursued courses of
      study in epidemiology, nutrition sciences, health behavior, environmental health
      sciences, biostatistics, or public health nutrition; and research projects in
      cessation of tobacco use, cancer screening, cancer epidemiology, diet
      modification, nutrient-cancer relationships, statistical modeling of
      carcinogenesis, medical-nutrition education, and obesity, in precise alignment
      with NCI cancer control objectives. Both courses and research projects have been
      interdisciplinary, taking advantage of the strong interdepartmental collaborative
      atmosphere at UAB. Former trainees have been successfully placed in academic,
      administrative, and practice positions in which they can strategically apply
      their cancer prevention and control expertise.

PMID- 10879894
TI  - Cancer control knowledge, attitudes, and perceived skills among medical students.
AB  - BACKGROUND: The Cancer Prevention and Control Education (CPACE) program aims to
      strengthen and coordinate curriculum offerings in cancer prevention and control
      for medical, graduate nursing and public health students. METHODS: Students were
      surveyed on cancer-related knowledge and confidence as part of needs assessment
      and evaluation efforts. The students completed self-administered surveys
      (response rate 78%). Descriptive and stratified analysis and ANOVA were
      conducted. RESULTS: Knowledge and confidence generally increased with each
      successive class year, but confidence varied markedly across specific counseling
      scenarios and by gender. While the students overall reported greater confidence
      in performing an examination than in interpreting the results, confidence varied
      significantly across specific types of examinations. CONCLUSIONS: Understanding
      of basic information about common cancers was disappointing. Confidence to
      perform and interpret examinations could be higher, especially for opposite
      gender screening examinations. Implications of the findings for CPACE curriculum
      development are discussed.

PMID- 10879895
TI  - Health professionals' baseline knowledge of oral/pharyngeal cancers.
AB  - BACKGROUND: The purpose of this study was to evaluate: self-perceived competency
      in screening for oral/pharyngeal cancers (OPCs); knowledge about their signs,
      symptoms, and risk factors; and percentage of patients routinely examined.
      METHODS: Of 352 health professionals who completed an assessment, a subgroup of
      110 physicians and dental providers was identified. Thirty-three of those had
      advanced training (AT) related to the oral cavity and 77 were primary care
      physicians (PCPs). RESULTS: Only 7% of the PCPs reported examining 100% of their
      patients for OPCs. A greater percentage of the PCP group than the AT group felt
      their knowledge about OPCs was not up to date (p < 0.05) and inaccurately
      identified common signs and sites of early OPCs. A greater percentage (p < 0.05)
      of the PCP group also reported the need for additional training. CONCLUSION:
      These results suggest the need for OPC educational programs aimed toward health
      care providers without advanced training related to the oral cavity.

PMID- 10879896
TI  - Promoting cancer prevention activities among Vietnamese physicians in California.
AB  - BACKGROUND: To promote prevention and early detection of cancer, the authors
      conducted a three-year intervention targeting Vietnamese physicians in solo
      practice in California. METHODS: Twenty subjects who had received their medical
      training in Vietnam were recruited into a randomized controlled trial. The
      intervention included computerized or manual cancer screening reminders,
      continuing medical education seminars, Vietnamese-language health education
      materials, newsletters, and oncology data-query programs. Evaluation included
      chart audits for eight targeted activities pre- and post-intervention. RESULTS:
      Before the intervention, annual physician performance rates were low for all
      eight activities: routine checkups (65.6%), Pap testing (13.8%), pelvic
      examinations (19.8%), clinical breast examinations (13.3%), mammography (6.4%),
      hepatitis B serologies (21.9%), hepatitis B immunizations (12.8%), and smoking
      cessation counseling (1.6%). After the intervention, performance rates increased
      significantly for smoking cessation counseling (p = 0.02), Pap testing (p =
      0.004), and pelvic examinations (p = 0.01). CONCLUSIONS: The results demonstrate
      the efficacy of an intervention targeting Vietnamese primary care physicians in
      promoting smoking cessation counseling, Pap testing, and pelvic examinations, but
      not other cancer prevention activities.

PMID- 10879897
TI  - Cigarette smoking patterns in patients after treatment of bladder cancer.
AB  - BACKGROUND: Assessment of smoking status and identification of those most likely
      to continue smoking are important in the management of patients who have bladder
      cancer, because continued smoking following diagnosis and treatment increases the
      likelihood of treatment-related complications, recurrence, second primary
      malignancies, and morbidity and mortality. METHODS: Patients (n = 224) receiving
      follow-up care of previously treated bladder cancers completed a brief written
      survey assessing their post-diagnosis smoking patterns. RESULTS: Despite the
      risks of continued smoking, 69% of the patients who had been active smokers at
      the time of diagnosis (n = 84) reported smoking at some point following the
      diagnosis and 45% reported smoking at the time of assessment. Patients diagnosed
      at earlier stages were more likely to continue smoking. Patients diagnosed at
      later stages were 2.80 times more likely to be continuous abstainers than those
      diagnosed sooner (95% CI, 1.08-7.25). CONCLUSIONS: The findings underscore the
      need to assess smoking status and provide smoking-cessation advice and counseling
      within routine comprehensive care of bladder cancer patients.

PMID- 10879898
TI  - Austrian women's attitudes toward and knowledge of breast self-examination.
AB  - BACKGROUND: Education of women to perform breast self-examination is a main
      objective of cancer societies worldwide. METHODS: By means of a questionnaire,
      975 healthy women in an Austria-wide population-based cross-sectional study were
      asked about their knowledge of breast self-examination (BSE) and mammography, and
      their cancer histories. RESULTS: 92% of the women knew BSE but only 31% practiced
      it thoroughly. Women living in rural communities with a life companion and
      younger women were more likely to practice BSE. Women who had family histories of
      cancer, especially older women, performed BSE significantly more often. There was
      a trend towards increasing BSE with increasing personal perception of the risk of
      cancer, especially among older women. The study showed a positive association
      between BSE and screening mammography. CONCLUSIONS: Although knowledge of BSE is
      widespread, it is actually practiced by only one third of women. Older women but
      not young women carry out BSE significantly more often when they have family
      histories of cancer. Information campaigns should target specific groups and
      emphasize the effectiveness of properly done BSE.

PMID- 10879899
TI  - Using evaluation methods to guide the development of a tobacco-use prevention
      curriculum for youth: a case study.
AB  - BACKGROUND: Fundamental to the development of educational programs and curricula
      is the evaluation of processes and outcomes. Unfortunately, many otherwise well
      designed programs do not incorporate stringent evaluation methods and are limited
      in measuring program development and effectiveness. Using an advertising lesson
      in a school-based tobacco-use prevention curriculum as a case study, the authors
      examine the role of evaluation in the development, implementation, and
      enhancement of the curricular lesson. METHODS: A four-phase formative and
      summative evaluation design was developed to divide the program-evaluation
      continuum into a structured process that would aid in the management of the
      evaluation, as well as assess curricular components. RESULTS AND CONCLUSIONS:
      Formative and summative evaluation can provide important guidance in the
      development, implementation, and enhancement of educational curricula. Evaluation
      strategies identified unexpected barriers and allowed the project team to make
      necessary "time-relevant" curricular adjustments during each stage of the
      process.

PMID- 10879900
TI  - Monitoring progress against cancer with age-adjusted rates and trends: what role
      does the standard population play?
AB  - BACKGROUND: Age-adjusted rates and statistical measures used to assess these
      rates are commonly used in cancer research to monitor progress against this
      disease. Trends in age-adjusted rates and related summary statistics may depend
      on the standard population used for age adjustment. Hence, knowledge of how the
      selected standard population influences such rates is essential for analysis and
      interpretation of the results. METHODS: The current paper evaluates age-specific
      and age-adjusted trends for the three leading causes of cancer mortality in the
      United States: lung and prostate cancers for males, and lung and breast cancers
      for females. RESULTS, CONCLUSIONS: The analysis shows that the choice of the
      standard population for age adjustment of the rates can influence one's
      perception of the progress being made against cancer.

PMID- 10879901
TI  - On doctoring.

PMID- 10879902
TI  - Pathologic and bacteriologic findings in 27-week-old commercial laying hens
      experimentally infected with Salmonella enteritidis, phage type 4.
AB  - Two strains of 27-wk-old commercial laying chickens (strain A, brown-egg-laying
      type and strain B, white-egg-laying type) were inoculated either orally (PO) or
      intravenously (IV) with a field isolate of Salmonella enteritidis phage type 4.
      Chickens were sequentially necropsied at regular intervals throughout the 17-wk
      observation period. Gross and microscopic lesions were most evident between 1 and
      14 days postinoculation (DPI). Gross lesions consisted of enlarged livers with
      white foci, enlarged and mottled white spleens, fibrinous exudate in the
      peritoneum, and atretic, misshapen ovarian follicles. Microscopic lesions
      included multifocal coagulative necrosis of hepatocytes and inflammation,
      fibrinous exudation in vascular sinuses of the spleen, and fibrinosuppurative
      inflammation of the peritoneum and ovarian follicles. The proportion of
      reproductive organ infections (ovary and oviduct) in the IV group, 83% (20/24, P
      = 0.007; 50% and 33% for strains A and strain B birds, respectively), was higher
      than that of the PO group, 46% (11/24; 29% and 17% for strains A and B,
      respectively), for the first 16 days of observation postinoculation. The
      proportion of fecal shedding for the IV group of birds was significantly (P =
      0.009) lower, 29% (7/24; 33% and 25% respectively for strain A and strain B
      birds, respectively), than the PO group, 67% (16/24; 75% and 58% for strain A and
      strain B birds, respectively). Three (2.6%) of 234 egg pools were culture
      positive for group D Salmonella from strain A chickens (1 of 119 pools from the
      IV group and 2 of 115 pools from the PO group of birds). Chickens infected with
      the field strain of S. enteritidis phage type 4 harbored the organism in tissues
      only for a brief time, most clearing within 8 DPI and nearly all within 16 DPI.
      Overall the percentage of culture-positive birds did not differ significantly (P
      > 0.05) between birds with and without lesions, but isolation of S. enteritidis
      tended to be more frequent when lesions were evident. This experiment also
      demonstrated that brown-egg-laying-type chickens were more susceptible than white
      egg-laying-type chickens to S. enteritidis phage type 4 isolated from California
      based on gross and microscopic lesions and bacteriologic findings.

PMID- 10879903
TI  - Results of a Salmonella enteritidis vaccination field trial in broiler-breeder
      flocks in The Netherlands.
AB  - From August 1995 until December 1997, the effect of adding Salmonella enteritidis
      (SE) vaccination to a certified standardized biosecurity program in a situation
      of increased infection risk was examined in a field trial in The Netherlands. In
      this field trial, two groups of broiler-breeder flocks with increased infection
      risk were vaccinated, one group with VAC-T/TALOVAC logSE(group A) and the second
      group with SALENVAC (group B). The determination of increased infection risk in
      groups A and B was based on an SE infection history; flocks were either
      previously infected and treated (PIT) or had other risk factors than previously
      infected and treated (OPIT). SE infections in both vaccinated groups were
      assessed by monitoring according to the Dutch salmonella control program. Under
      field conditions, designation of a vaccinated and a control group on the farm was
      not possible. In the same period as the vaccinated groups, 608 nonvaccinated
      flocks (group C) were hatched and monitored according to the Dutch salmonella
      control program. The flock level occurrence of SE infection in the vaccinated
      groups was compared with the flock level occurrence of SE infection in the
      nonvaccinated group on the basis of comparability of infection risk. In group C,
      whether or not flocks had infection risk PIT was known and for risk factor OPIT,
      only whether or not a flock had been placed on a previously contaminated farm (=
      risk of reinfection) was known. The proportion of SE-infected flocks with risk
      factor PIT in the vaccinated groups was not significantly different from that in
      the nonvaccinated group C. Only the proportion of SE-infected flocks with a risk
      of reinfection in the vaccinated group B (0) was significantly lower (P = 0.02)
      than in the nonvaccinated group C (18%). The fact that no significant result was
      found in favor of group A is because of the small number of flocks in this part
      of the study. On the basis of the conditions of the setup of this trial, it can
      only be concluded that there is an indication that vaccination contributes in the
      reduction of SE reinfection in broiler breeder flocks.

PMID- 10879904
TI  - Identifying agent(s) associated with poult enteritis mortality syndrome:
      importance of the thymus.
AB  - Poult enteritis mortality syndrome (PEMS), a highly infectious disease of young
      turkeys, causes serious financial losses to the turkey industry. Clinically, PEMS
      is defined by mortality profiles, diarrhea, growth depression, and
      immunosuppression. Although many viruses, bacteria, and parasites are found in
      PEMS-infected birds, the inciting agent remains unknown. Experimentally, PEMS can
      be reproduced by exposing naive poults to the intestinal contents from infected
      birds. Previous reports suggest that extraintestinal tissues fail to reproduce
      the disease. Histopathologic examination of tissues from PEMS-infected poults
      suggested that the thymus exhibited the earliest signs of pathology. On the basis
      of these observations, we hypothesized that the thymus harbors an agent(s)
      involved in PEMS. In these studies, naive turkey poults were orally inoculated
      with a bacteria-free filtrate composed of either the intestines and feces or the
      thymus from PEMS-infected birds and were monitored for clinical signs of PEMS.
      Poults exposed to a filtrate composed solely of the thymus from PEMS-infected
      birds exhibited diarrhea, growth depression, mortality, pathology, and, most
      importantly, immunosuppression similar to poults exposed to the intestinal
      filtrate. The results of this study suggest that the thymus of infected birds
      harbors the agent(s) that can reproduce a PEMS-like disease in turkey poults.

PMID- 10879905
TI  - Diagnosis of duck plague in waterfowl by polymerase chain reaction.
AB  - A recently developed polymerase chain reaction (PCR) assay was used for diagnosis
      of duck plague in waterfowl tissues from past and current cases of waterfowl
      mortality and to identify duck plague virus in combined cloacal/oral-pharyngeal
      swab samples from healthy mallards (Anas platyrhynchos) after a disease outbreak.
      The PCR was able to detect viral DNA from all the individual or pooled tissues
      assayed from 10 waterfowl, including liver and spleen samples from three Muscovy
      ducks (Cairina moschata domesticus) that did not yield virus isolates. The strong
      staining intensity of the PCR products from the waterfowl tissues indicated that
      large amounts of virus were present, even when virus was not isolated. Duck
      plague DNA was also detected in a cloacal swab sample from a wood duck (Aix
      sponsa) carcass submitted for diagnosis. The PCR assay identified duck plague DNA
      in 13 swab samples that produced virus isolates from carrier mallards sampled in
      1981 after a duck plague die-off. The duck plague PCR clearly demonstrated the
      ability to quickly diagnose duck plague in suspect mortality cases and to detect
      virus shed by carrier waterfowl.

PMID- 10879906
TI  - A novel "small round virus" inducing poult enteritis and mortality syndrome and
      associated immune alterations.
AB  - The role of a novel "small round virus" (SRV) isolated from poult enteritis and
      mortality syndrome (PEMS) cases in inducing PEMS and associated immune
      alterations was examined in this study. Specific-pathogen-free and conventional
      poults were orally challenged with SRV and/or turkey coronavirus and monitored
      for clinical signs. Intestines, thymus, bursa, and spleens were examined for SRV
      antigen at various days postinoculation (DPI). Peripheral blood lymphocytes
      (PBLs), thymocytes, and splenic lymphocytes from inoculated poults or lymphocytes
      isolated from healthy poults after incubation with SRV in vitro were examined for
      lymphoproliferative potential against concanavalin A (Con A). The incidence of
      lymphocyte subpopulations in the peripheral blood and thymic lymphocytes of SRV
      challenged poults was examined by flow cytometry. The results of these studies
      showed that the SRV challenge induced diarrhea, growth suppression, and atrophy
      of thymus and bursa resembling those of PEMS in field and/or experimental
      infections. The SRV antigen was detected in intestinal tissues soon after
      infection (i.e., at 2 and 4 DPI), whereas lymphoid tissues such as thymus, bursa,
      and spleen were positive for SRV antigen starting at 4 DPI until 8 DPI,
      suggesting virus translocation to lymphoid organs. The responsiveness of PBLs to
      Con A at 2 DPI was significantly reduced in all virus challenge groups (e.g., 28%
      and 22% in the SRV-alone group in studies 1 and 2, respectively) below the
      uninfected group. However, this suppressed response was no longer evident in the
      SRV group by 7 DPI. The SRV incubation with normal thymocytes and splenocytes in
      vitro resulted in significantly reduced lymphoproliferative response against Con
      A (41.2% and 10.49% reductions at 1:50 SRV dilution vs. controls in thymocytes
      and splenocytes, respectively). Flow cytometry analysis revealed a sudden decline
      at 2 DPI in the numbers of CD4- CD8+ lymphocyte subset in PBLs of SRV-infected
      poults. However, by 8 DPI, SRV-challenged poults had relatively higher CD4- CD8+
      lymphocytes in PBLs. On the contrary, thymocytes had higher percentages of CD4-
      CD8+ lymphocytes at 2 and 4 DPI and reached comparable levels at 8 DPI in
      controls and SRV-infected poults. No differences were observed in CD4+ CD8-
      lymphocyte numbers in controls vs. SRV-infected poults. The findings of these
      studies imply that SRV may be a promising primary etiologic agent of PEMS.
      Furthermore, the SRV infection may compromise the lymphocyte-mediated immune
      defenses by reducing lymphoproliferation and the CD4- CD8+ (presumably T
      cytotoxic cells) lymphocytes during the acute stage of SRV infection.

PMID- 10879907
TI  - Infectious bursal disease live vaccines: changes in the virus population during
      serial passage in chickens and chicken embryo fibroblast cells.
AB  - Two attenuated infectious bursal disease virus strains used as commercial live
      vaccine were passaged five successive times in specific-pathogen-free chickens
      and chicken embryo fibroblast (CEF) cells. Both attenuated strains increased in
      virulence during the passage in susceptible chickens as evidenced by the decrease
      in bursa/body weight ratios. A direct nucleotide sequence analysis of the VP2
      hypervariable domain amplified by the reverse transcription-polymerase chain
      reaction revealed that the nucleotide at position 890 (T) in both strains was A
      after the passage in chicken. In addition, the nucleotide at position 890 (A) was
      T or C after the subsequent passage in CEF cells. Because of the nucleotide
      differences, the amino acid residue at position 253 (His) in both vaccines was
      Gln after the passage in chickens, and the amino acid residue Gln was changed
      back to His during the subsequent passage in CEF cells. The digestion of the
      amplified fragment with restriction endonucleases Stul and Ncol, which recognize
      the sequence difference at position 890, showed that the population of the virus
      that had amino acid Gln at position 253 was gradually increased during the
      passage in chickens. Conversely, the population of the virus that had amino acid
      His at position 253 was gradually increased during the subsequent passage in CEF
      cells.

PMID- 10879908
TI  - Establishment of an enzyme-linked immunosorbent assay with a coated deflagellated
      Salmonella enteritidis antigen for detection of a specific chicken antibody.
AB  - We attempted to establish an enzyme-linked immunosorbent assay (ELISA) for field
      monitoring/profiling purposes for Salmonella enteritidis (SE) infection of
      poultry flocks. Serotyping rabbit sera, commercially obtained, specific for
      Salmonella identification sera to O2, O4, O7, O8, S. Vi, S. Hm, and O9, showed
      negative ELISA (E)-values (< 0.2) on ELISA, except the O9 identification serum (E
      value > 0.5). Similar negative E-value results were obtained for antisera to
      Echerichia coli (E. O antigen). Field serum samples originating from SE-isolated
      flocks yielded similar positive ratios on both ELISAs including the present
      coated deflagellated SE antigen and a commercially obtained flagellated SE
      antigen and that of rapid plate aggregation with a pullorum antigen (PD-RPA).
      About 100 days after the first monitoring, no SE isolation in the same flock was
      observed resulting in a carrier state of SE infection. Although both the
      monitoring results with commercially obtained ELISA and PD-RPA showed lower
      positive or negative ratios, the present ELISA showed a higher positive ratio
      than that of the first monitoring. The present ELISA is suggested to be a
      suitable method to do accurate profiling on the carrier state of infection.

PMID- 10879909
TI  - Viral agents associated with poult enteritis and mortality syndrome: the role of
      a small round virus and a turkey coronavirus.
AB  - Intestinal samples from turkey poults affected with poult enteritis and mortality
      syndrome (PEMS) were examined for viruses by immune electron microscopy and
      double-stranded RNA virus genome electropherotyping. Turkey coronavirus (TCV),
      avian rotaviruses, reovirus, and a yet undefined small round virus (SRV) were
      detected. The SRV and TCV were isolated and propagated in turkey embryos.
      Challenge of specific-pathogen-free turkey poults with SRV, TCV, or both resulted
      in mortality and clinical responses similar to those of natural PEMS. Our
      experiments indicate that SRV and TCV are possibly important agents in the
      etiology of PEMS and the combination of these infections might result in
      outbreaks with high mortality. The severity of clinical signs and mortality of
      PEMS are postulated to be partly related to the virus agents involved in
      individual outbreaks.

PMID- 10879910
TI  - Kinetic differences in intestinal and systemic interferon-gamma and antigen
      specific antibodies in chickens experimentally infected with Eimeria maxima.
AB  - Kinetic differences between systemic vs. intestinal and humoral vs. cellular
      immune responses were elucidated in chickens experimentally infected with Eimeria
      maxima by comparing interferon-gamma (IFN-gamma) and parasite-specific antibody
      levels in the intestine and serum during the course of infection. The level of
      serum IFN-gamma correlated significantly with fecal oocyst shedding (r2 = 0.97),
      thereby establishing the importance of cell-mediated immunity in coccidia
      infection. Moreover, intestinal IFN-gamma levels increased sooner than those in
      sera (4 vs. 6 days postinfection) and both were observed prior to the appearance
      of parasite-specific antibodies (8-10 days postinfection), again indicating the
      importance of intestinal cellular immunity in coccidiosis. Although
      immunoglobulin (Ig)G, IgA, and IgM isotypes of the antigen-specific antibody
      response increased significantly in both the intestine and serum after E. maxima
      infection, intestinal IgA-specific antibodies showed the most dramatic increase.
      However, the relevance of this observation in the context of primary Eimeria
      infection is unclear because the coccidia parasites have reached the final stages
      of their life cycle by this time. These results thus demonstrate the importance
      of T-cell immune responses against coccidia, characterized by local IFN-gamma
      secretion in the intestine, in mediating host protective immune response to
      coccidia.

PMID- 10879911
TI  - The fluorescent antibody and indirect fluorescent antibody assays for diagnosing
      stunting syndrome of turkeys.
AB  - The fluorescent antibody (FA) assay was developed for detecting the stunting
      syndrome agent (SSA) from intestinal tissue. Similarly, the indirect fluorescent
      antibody (IFA) assay was developed for detecting serum antibodies to SSA.
      Convalescent antiserum from turkeys orally immunized with SSA was found to be the
      primary antibody of choice for the FA assay. Intestinal jejunal samples from
      poults inoculated 3-4 days postinoculation (DPI) was found to be the best antigen
      source for the IFA assay. SSA was detected from the intestinal tracts of
      experimentally inoculated birds at 2 DPI with highest level of reactivity at 3
      DPI by the FA assay. After 4 DPI the level of SSA infectivity of the intestines
      waned to low levels. Serum antibody was detected from experimentally inoculated
      birds as early as 7 DPI with all birds tested seroconverting by 12 DPI. These
      assays should prove useful for future studies concerning stunting syndrome.

PMID- 10879912
TI  - Chicken embryo lethality assay for determining the virulence of avian Escherichia
      coli isolates.
AB  - Multiple isolates of Escherichia coli from clinical cases of colibacillosis and
      E. coli from the intestinal tracts of normal broilers at slaughter were assayed
      by the embryo lethality test to determine their virulence. The assay was repeated
      five times in order to establish reproducibility and determine the statistical
      parameters of the test. This study showed that the inoculation of approximately
      100 colony-forming units in the allantoic cavity of 12-day-old embryos
      discriminated between virulent and avirulent E. coli isolates. Gross lesions
      included cranial and skin hemorrhages in addition to encephalomalacia in embryos
      inoculated with virulent isolates. Abnormalities were observed by microscopic
      examination of the heart, brain, and liver in embryos inoculated with virulent
      isolates. Analysis of data indicated that the length of the test should be 4
      days. In the virulent group, day 2 postinoculation had the most significant death
      patterns. Sample size calculations indicated that 11 embryos are sufficient for
      the assay. On the basis of death rates, isolates considered to be avirulent had
      an embryo death rate of <10%, moderately or secondary pathogens had a 10%-29%
      death rate, and virulent isolates had a death rate of >29%. An important aspect
      of this assay is the accessibility of good-quality fertile embryonated eggs.

PMID- 10879913
TI  - Identification of avian infectious bronchitis virus by direct automated cycle
      sequencing of the S-1 gene.
AB  - Direct automated cycle sequencing (DACS) of a reverse transcription-polymerase
      chain reaction (RT-PCR) product of the S-1 subunit of the spike peplomer gene was
      used to identify infectious bronchitis virus (IBV) serotypes. Degenerate primers
      CK4 and CK2, utilized previously in our laboratory, were selected for DACS
      because they successfully amplify a wide range of serotypes represented by
      various reference strains and field isolates and the resulting polymerase chain
      reaction (PCR) product contains diagnostically relevant S-1 sequences that can be
      used to identify the serotype of IBV. The S-1 nucleotide sequences generated by
      DACS were aligned and analyzed with commercial software to determine their
      relationship to the S-1 nucleotide sequences of IBV strains on deposit in the
      GenBank and EMBL databases. Reference strains Massachusetts (Mass) 41,
      Connecticut (Conn), Arkansas (Ark) DPI, JMK, and DE/072/92 were initially tested
      by DACS to establish the feasibility of the procedure. The DACS procedure was
      further evaluated with a panel of "unknowns" comprised of IBV reference strains,
      field isolates, and variant serotypes collected by our laboratory. The DACS
      procedure provided high-quality and reproducible S-1 sequence for all IBV
      serotypes tested, including variant serotypes that had not been sequenced
      previously. The S-1 nucleotide sequences for the amplified PCR products of
      reference strains Mass 41, Conn, Ark DPI, JMK, and DE/072/92 generated by DACS
      were highly homologous (>99% nucleotide identity) with their respective GenBank
      database sequences. In the unknown panel, the nucleotide identities of the DACS S
      1 sequences of field isolates of serotypes previously identified by virus
      neutralization were also found to be very high (> or = 95.5%) after alignment
      with database sequences. In contrast, the nucleotide identities of S-1 sequences
      of variant serotypes 37, 3330, and PA/1220/98 and reference strain Clark 333, for
      which database sequences were not available, ranged from 27.7% to 73.8%, well
      below the identity values for a homologous serotype. With alignment software, the
      identities of strains in mixtures of RNAs of two different serotypes were not
      resolvable. DACS of IBV S-1 RT-PCR products will enable researchers to rapidly
      identify field strains, including new, previously unrecognized variant virus
      serotypes.

PMID- 10879914
TI  - Susceptibility of an avian pneumovirus isolated from Minnesota turkeys to
      physical and chemical agents.
AB  - Survival characteristics of a Minnesota avian pneumovirus (APV) isolated from a
      turkey nasoturbinate, propagated in tissue culture, and exposed to various
      physiochemical treatments were determined. These characteristics included
      survivability under various conditions. Specifically, APV was viable at
      temperatures of -70 C and -20 C for over 26 wk, 4 C for less than 12 wk, 20 C for
      less than 4 wk, 37 C for 48 hr, and 50 C for less than 6 hr. In addition, APV
      survived 12 freeze/thaw cycles with no loss of activity. With a variable pH for 1
      hr, the titer was unaffected between the levels of pH 5 and 9. Several
      disinfectants, including quaternary ammonia, ethanol, iodophor, a phenol
      derivative, a biguanide, and bleach, were all effective in reducing the viability
      of the virus. After 7 days of drying at room temperature, the APV remained viable
      and was recovered on cell culture.

PMID- 10879915
TI  - Increased tracheal colonization in chickens without impairing pathogenic
      properties of avian pathogenic Escherichia coli MT78 with a fimH deletion.
AB  - Several studies suggest that the expression of F1 fimbriae could be involved in
      the virulence of Escherichia coli for chickens. F1 fimbriae display multivalent
      properties such as adhesion to epithelia or interaction with the immune system
      that imply specific interactions between the adhesin FimH and different cell
      receptors. We constructed a delta fimH mutant of the avian pathogenic E. coli
      MT78 and evaluated its in vivo colonization and pathogenicity, as compared to
      that of the parent strain. The generated mutant PA68 was unable to adhere in
      vitro to chicken epithelial pharyngeal or tracheal cells; mutant bacteria were
      mostly afimbriated although a minority of them displayed altered piliation
      phenotypes. Two inoculation routes were used to compare the ability of MT78 and
      PA68 to colonize the respiratory tract and to induce colibacillosis in chickens.
      In the first model, 2-wk-old axenic chickens were inoculated intratracheally with
      one or both E. coli strains, after primary infection with infectious bronchitis
      virus. In the second model, 3-wk-old specific-pathogen-free chickens were
      inoculated via the caudal thoracic air sac. After intratracheal inoculation, the
      delta fimH mutant was found to be a better colonizer than MT78 in the trachea of
      inoculated chickens. Furthermore, when both strains were inoculated
      simultaneously, the delta fimH mutant constituted 98% of the bacterial population
      in the trachea at day 7 postinoculation. Irrespective to the inoculation route,
      MT78 and PA68 showed similar abilities to induce macroscopic lesions in chickens,
      to provoke bacteremia, and to colonize the internal organs. However, 4 days after
      intra-air sac inoculation, bacterial counts of the mutant were lower in the
      spleen and liver than those of MT78. Our results show that FimH is not required
      for colonization of the trachea of axenic chickens by E. coli and that it is not
      a major determinant of bacterial pathogenicity. On the contrary, the lack of
      expression of FimH seems to favor the in vivo colonization of the trachea of
      chickens by E. coli.

PMID- 10879916
TI  - Sequence analysis of related low-pathogenic and highly pathogenic H5N2 avian
      influenza isolates from United States live bird markets and poultry farms from
      1983 to 1989.
AB  - The last highly pathogenic outbreak of avian influenza in the United States was
      caused by an H5N2 influenza virus in Pennsylvania and New Jersey in 1983-84.
      Through a combined federal and state eradication effort, the outbreak was
      controlled. However, in 1986-89, multiple H5N2 viruses were isolated from poultry
      farms and the live bird markets (LBMs) in the United States. To determine the
      epidemiologic relationships of these viruses, the complete coding sequence of the
      nonstructural gene and the hemagglutinin protein subunit 1 of the hemagglutinin
      gene was determined for 11 H5N2 viruses and compared with previously available
      influenza sequences. The H5N2 isolates from 1986-89 were all closely related to
      the isolates from the 1983-84 Pennsylvania outbreak by nucleotide and amino acid
      sequence analysis for both genes, providing additional evidence that the
      Pennsylvania/83 (PA/83) virus lineage was not completely eradicated. The PA/83
      lineage also had a large number of unique amino acid changes not found in other
      avian influenza viruses, which was suggestive that this lineage of virus had been
      circulating in poultry for an extended period of time before the first isolation
      of virus in 1983. High substitution and evolutionary rates were measured by
      examining the number of nucleotide or amino acid substitutions over time as
      compared with the index case, CK/PA/21525/83. These rates, however, were similar
      to other outbreaks of avian influenza in poultry. This study provides another
      example of the long-term maintenance and evolution of influenza viruses in the
      U.S. LBMs and provides further evidence of the connection of the LBMs and the
      Pennsylvania 1983 H5N2 outbreak.

PMID- 10879917
TI  - Characterization of monoclonal antibodies against fowl poxvirus.
AB  - Vaccines for the prevention of fowl pox in chickens and turkeys have been
      available for more than five decades. However, in recent years outbreaks have
      occurred in several previously vaccinated chicken flocks. Presumably, fowl
      poxviruses (FPVs) antigenically different from the attenuated vaccine strains are
      responsible for such occurrences. In support of this concept, we previously
      detected minor antigenic changes in field isolates based on comparative
      immunoblotting with polyclonal anti-FPV serum. Realizing the need for antibodies
      specific against the dominant antigens of FPV, monoclonal antibodies (MAbs) were
      produced by immunizing mice with either a field strain of FPV or a pigeon
      poxvirus, currently used for vaccination. Three hybridoma clones producing MAbs
      reacting with a specific FPV protein were selected from a total of 83 clones. In
      immunoblots, two of the MAbs, P1D9 and P2H10, recognized an antigen with an
      apparent molecular weight varying from 39 to 46 kD, depending on the FPV strain.
      The third MAb, P2D4, reacted with an approximately 80-kD protein, regardless of
      which FPV isolate was tested. Immunofluorescent staining with P1D9 and P2D4
      revealed that these MAbs react with intracytoplasmic antigens in FPV-infected
      cells.

PMID- 10879918
TI  - Chlamydia-induced bilateral ectropion of the inferior eyelids in pigeons.
AB  - In this study we described four cases of bilateral ectropion in pigeons that were
      investigated in Greece. Anemia, leukocytosis, and increased levels of enzymes
      lactate dehydrogenase, aspartate aminotransferase, creatine phosphokinase, and
      total serum proteins were found. Chlamydial elementary bodies were observed by
      modified Ziehl-Neelsen stain in direct smears of conjunctiva, liver, and spleen
      as well as in yolk sac samples after egg inoculation with eyelid material.
      Histologically, significant hyperplasia of the conjunctival epithelium was
      observed. Using immunohistochemical methods, chlamydial antigen was revealed in
      eyelid, liver, and spleen paraffin sections. This study suggests that Chlamydia
      spp. was the causative agent that induced ectropion.

PMID- 10879919
TI  - A recombinant Eimeria protein inducing interferon-gamma production: comparison of
      different gene expression systems and immunization strategies for vaccination
      against coccidiosis.
AB  - A rabbit antiserum against an 18- to 27-kD native protein fraction (F3) from
      Eimeria acervulina merozoites identified a cDNA (3-1E) containing a 1086-base
      pair insertion with an open reading frame of 170 amino acids (predicted molecular
      weight, 18,523). The recombinant 3-1E cDNA expressed in Escherichia coli produced
      a 60-kD fusion protein and a 23-kD protein after factor Xa treatment of the
      fusion protein. Both proteins were reactive with the F3 antiserum by western blot
      analysis. A rabbit antiserum against a synthetic peptide deduced from the amino
      acid sequence of the 3-1E cDNA reacted with a 27-kD recombinant 3-1E protein
      expressed in Sf9 insect cells and a 20-kD native protein expressed by E.
      acervulina sporozoites and Eimeria tenella sporozoites and merozoites. By
      immunofluorescence staining, a monoclonal antibody produced against the
      recombinant 3-1E protein reacted with sporozoites and merozoites of E.
      acervulina, E. tenella, and Eimeria maxima. Spleen lymphocytes from E. acervulina
      immune chickens showed antigen-specific proliferation and interferon (IFN)-gamma
      production upon stimulation with the recombinant 3-1E protein, indicating that
      the protein activates cell-mediated immunity during coccidiosis. Immunization of
      chickens with either the E. coli- or Sf9-expressed recombinant 3-1E protein with
      adjuvant, or direct injection of the 3-1E cDNA, induced protective immunity
      against live E. acervulina. Simultaneous injection of the recombinant 3-1E
      protein, or the 3-1E cDNA, with cDNAs encoding chicken IFN-gamma or interleukin
      (IL)-2/15 further enhanced protective immunity. These results indicate that the
      recombinant E. acervulina 3-1E cDNA or its polypeptide product may prove useful
      as vaccines against avian coccidiosis.

PMID- 10879920
TI  - Antibody responses to La Sota strain vaccines of Newcastle disease virus in
      ostriches (Struthio camelus) as detected by enzyme-link ed immunosorbent assay.
AB  - Because of the fact that South Africa is a Newcastle disease virus (NDV)-endemic
      country, major concerns exist that the export of ostrich meat could transmit
      velogenic strains of this disease. The ability to transmit the virus could be
      reduced by effective vaccination of South African ostriches. In this study, two
      vaccination trials were conducted to assess serum antibody production in response
      to vaccination with La Sota strain NDV vaccines. To this end, a commercially
      available chicken anti-NDV enzyme-linked immunosorbent assay (ELISA) was modified
      for the detection of anti-NDV antibodies in ostrich serum. The results obtained
      with this ELISA were verified by comparison with an indirect ELISA. In the first
      trial, ostriches were immunized subcutaneously four times with different volumes
      of an inactivated vaccine and their immune response was determined from 2.5 mo up
      to the ideal slaughter age of 14 mo. Results indicated that ostriches responded
      in a dose-dependent manner and gave support for the vaccination schedule
      currently recommended to South African farmers. In a second trial, immunization
      by eyedrop with a live La Sota vaccine of 5-wk-old ostriches did not elicit a
      humoral immune response. The results indicate that it is highly unlikely that
      ostriches that have been vaccinated according to the recommended vaccination
      schedule can transmit the virus.

PMID- 10879921
TI  - Immunohistochemical detection of Mycoplasma gallisepticum antigens in turkey
      respiratory tissues.
AB  - An avidin-biotin-immunoperoxidase diagnostic test was developed to facilitate
      rapid identification of Mycoplasma gallisepticum in respiratory tissues of
      turkeys. This procedure used polyclonal primary antibodies produced in rabbits.
      Turkeys were inoculated into the infraorbital sinus and trachea with the R strain
      of M. gallisepticum, Mycoplasma synoviae, Mycoplasma meleagridis, or Frey's
      media. The outer walls of the infraorbital sinuses, lungs, and tracheas were
      collected and fixed in either 10% neutral formalin or pentanedial methyl glycol
      at 1, 2, 3, and 4 wk postinoculation. Tissues were subdivided and remained in
      each fixative for 6 or 24 hr. The avidin-biotin-immunoperoxidase diagnostic test
      was sufficiently sensitive to detect M. gallisepticum antigen at 1, 2, 3, and 4
      wk postinoculation. Staining of M. gallisepticum was significantly more intense
      on infraorbital sinus epithelium than on respiratory epithelium from the trachea
      or lung. Statistical analysis indicated that the 6-hr fixation time offered
      better antigen preservation than 24 hr in a fixative. There was no difference in
      intensity of M. gallisepticum antigen staining in tissues fixed in methyl
      pentanedial glycol when compared with tissues fixed in 10% neutral buffered
      formalin. Significant differences in staining intensity were observed between
      weeks. Specificity of the avidin-biotin-immunoperoxidase test was not complete.
      None of the tissues from the M. meleagridis and control groups showed staining.
      No staining was observed in the ciliated brush border of infraorbital sinus
      epithelial cells from turkeys infected with M. synoviae. However, weak to
      moderate staining was observed in several tracheas of turkeys inoculated with M.
      synoviae. Improved specificity of an avidin-biotin-immunoperoxidase diagnostic
      test to detect M. gallisepticum in respiratory tissues of turkeys probably will
      require the use of multiple monoclonal antibodies directed against several
      different epitopes specific to the cell membrane of M. gallisepticum.

PMID- 10879922
TI  - Avian coccidiosis. A review of acquired intestinal immunity and vaccination
      strategies.
AB  - The gut-associated lymphoid tissues contain B and T lymphocytes responsible for
      acquired immunity to avian coccidiosis. Intestinal B cells begin producing
      parasite-specific antibodies shortly after infection although their role in
      protecting against coccidiosis is debated. T-cell-mediated immunity,
      predominantly by intestinal intraepithelial lymphocytes and lamina propria
      lymphocytes, confers the main component of protective immunity to Eimeria. Many
      of these cells display the CD8 and gammadelta T-cell receptor surface antigens,
      phenotypic markers of cytotoxic T cells. Although their role in eliminating
      Eimeria infection remains to be completely elucidated, T cells have been
      implicated in parasite transport, and their activity is augmented by interferon
      gamma and interleukin-2. Because of the importance of cell-mediated immunity,
      coccidiosis vaccines must be capable of stimulating intestinal T cells. Orally
      delivered, live parasite vaccines, either unattenuated or attenuated, are
      powerful stimulators of intestinal cell-mediated immunity, but antigenic
      variability between Eimeria species present in the vaccine and in the field may
      restrict their commercial application. The newer generations of recombinant DNA
      and subunit protein vaccines, particularly when used in conjunction with
      interferon-gamma and interleukin-2, have shown preliminary promise in controlling
      experimental infections but have yet to be commercially developed.

PMID- 10879923
TI  - Characterization of the stunting syndrome agent: physicochemical properties.
AB  - Stunting syndrome is an enteric disease of turkeys causing diarrhea, reduced
      weight gain, poor feed efficiency, and maldigestion. The etiologic agent is a
      newly identified, but unclassified, virus termed the stunting syndrome agent
      (SSA). The SSA is a pleomorphic, enveloped virus ranging from 60 to 95 nm in
      diameter. The objectives of this study were to characterize the physicochemical
      properties of SSA. SSA hemagglutinated rat erythrocytes at 4 C and room
      temperature. Treatment of SSA with ether resulted in loss of infectivity. SSA was
      resistant to pH changes between pH 3.0 and pH 9.0 at 37 C for 1 hr. The virus was
      inactivated at pH > or = 10. SSA was resistant to treatment with trypsin,
      chymotrypsin, pancreatin, phospholipase C, and sodium deoxycholate. Treatment of
      SSA with trypsin, chymotrypsin, and pancreatin resulted in enhanced viral
      infectivity. The viral genome extracted from purified SSA was sensitive to RNAse
      treatment. Using oligo d(T)16-18 and random hexamers as primers, the SSA genome
      was amplified using the reverse transcription-polymerase chain reaction
      conditions but was not amplified using polymerase chain reaction conditions. The
      enrichment of viral genome was achieved following poly-A+ selection. These
      studies provide evidence that the SSA is a positive-sense, single-stranded RNA
      virus having many characteristics (stability at acidic pH, resistant to
      proteolytic enzymes and bile salt) consistent with other enveloped enteric
      viruses.

PMID- 10879924
TI  - Phenotypic variation of Mycoplasma iowae surface antigen.
AB  - The diseases caused by mycoplasmas are generally chronic and persistent and
      apparently occur notwithstanding a host immune response. The ability to evade the
      host immune response is facilitated by phenotypic variation in the mycoplasma
      surface components. The avian mycoplasmas Mycoplasma gallisepticum and Mycoplasma
      synoviae have both been previously described to be able to switch their surface
      antigens, and recent evidence indicates that M. gallisepticum could switch
      surface antigens under natural conditions in vivo. In this work we present data
      to support that Mycoplasma iowae is also capable of phenotypic variation as
      detected by reactions with the monoclonal antibody MAb MI1 on colony immunoblots.
      This phenomenon is suggested to occur spontaneously or in response to normal
      serum and tissue components and may play an important role in the evasion of the
      host immune response.

PMID- 10879926
TI  - Eustrongylidiasis in eastern great blue herons (Ardea herodias).
AB  - The nematode Eustrongylides ignotus was found in peritoneal lesions of several
      great blue herons (Ardea herodias) submitted for necropsy from a wildlife
      rehabilitation center in northern Delaware. Prior to death, signs of disease
      included ataxia, emaciation, weakness, and anemia. Blood collection was not
      uniformly performed, but in cases where it was performed, affected birds
      demonstrated abnormal clinical hematology. Postmortem findings included numerous
      lesions associated with verminous peritonitis. Significant histologic
      granulomatous response to the presence of these organisms was noted, particularly
      in the proventricular specimens. Other organs involved included intestine,
      spleen, pancreas, and liver.

PMID- 10879925
TI  - Passively administered antibodies alleviate stunting syndrome in turkey poults.
AB  - Stunting syndrome is an enteric disease of young turkeys that results in reduced
      growth (stunting) of poults and impaired feed efficiency. A virus, which has been
      termed the stunting syndrome agent (SSA), causes stunting syndrome. In this study
      passive immunity was evaluated as a method of protecting poults from stunting
      syndrome. One-day-old poults were injected with either tryptose phosphate broth,
      an anti-SSA antibody preparation, or an anti-Newcastle disease virus antibody
      preparation before challenge by placing them into SSA-contaminated isolators or
      control (nonchallenge) isolators. Poults that received anti-SSA antibodies were
      significantly heavier (P < 0.05) and did not display as severe clinical disease
      compared to birds that did not receive the anti-SSA antibodies. However, the
      birds that received anti-SSA antibodies and were challenged were significantly
      lighter (P < 0.05) than birds that were not challenged. The results of this trial
      demonstrate that the injection of anti-SSA antibodies benefited poults undergoing
      stunting syndrome. The role of passive immunity, either through breeder hen
      vaccination or through supplying antibodies to poults artificially (i.e., at the
      hatchery), may have future applications in alleviating stunting syndrome.

PMID- 10879927
TI  - Polytetrafluoroethylene gas intoxication in broiler chickens.
AB  - A poultry research facility that housed 2400 Peterson x Hubbard cross broilers
      (48 pens of 50 chicks each) experienced 4% mortality within 24 hr of chick
      placement. Mortality started within 4 hr of placement, and within 72 hr,
      cumulative mortality had reached 52%. Mild dyspnea was the only clinical sign
      noted in some chicks prior to death. The primary gross lesion noted in the chicks
      submitted was moderate to severe pulmonary congestion. The lungs of four of these
      chicks sank in formalin, and blood-tinged fluid was noted in the mouth and nares
      of two chicks. The microscopic lesions noted in the affected chicks were moderate
      to severe pulmonary edema and congestion. The diagnosis indicated to the
      submitter was that pulmonary edema caused by exposure to an unidentified noxious
      gas caused the death of the chicks. The poultry house environment was tested for
      sulfur dioxide, oxides of nitrogen, carbon monoxide, carbon dioxide, and volatile
      organic compounds (as produced by combustion engines); all tests were negative
      for significant levels of these compounds. A second broiler flock was placed in
      the same facility and the mortality at 6 wk was 11%, which was greater than the
      2.5%-4.7% mortality seen in the previous four flocks on the farm. Further
      investigation revealed that the only change in management practice in this
      facility prior to the onset of the severe mortality problem was the replacement
      of 48 heat lamp bulbs (one for each pen). The new heat lamp bulbs were
      polytetrafluoroethylene (PTFE) coated. PTFE gas intoxication has been reported in
      several exotic avian species, but this intoxication has not been previously
      reported in a poultry flock.

PMID- 10879928
TI  - Atrophy of the primary lymphoid organs of meat pigeons in Italy associated with
      circoviruslike particles in the bursa of Fabricius.
AB  - During a survey effected in a meat pigeon slaughterhouse of central Italy,
      atrophy of primary lymphoid organs (bursa of Fabricius and thymus) and hypoplasia
      of bone marrow were observed. Histologic, ultrastructural, and hematologic
      examinations were performed on a total of 80 randomly selected 30-day-old meat
      pigeons. By histologic studies, lymphocytic depletion and necrosis with cyst
      formations in the bursa of Fabricius were detected in all subjects that showed
      thymus and bursa atrophy at necropsy. Basophilic intranuclear inclusions were
      also observed in bursal cells. After ultrastructural studies, these inclusions
      were proved to be viral particles resembling circoviruslike particles in
      morphology and size. Severe lymphocytic depletion of the bursa was plausibly
      associated with the presence of the viral particles.

PMID- 10879930
TI  - Diagnosis of atoxoplasmosis in a canary (Serinus canarius) by histopathologic and
      ultrastructural examination.
AB  - Our paper describes pathologic and ultrastructural features of a canary (Serinus
      canarius) infected by Atoxoplasma sp. Histologically, numerous mononuclear cells
      were observed in intestinal mucosa, liver, and spleen. Most of these cells
      contained a variable number of protozoal-like organisms. These organisms were
      identified as Atoxoplasma sp. by ultrastructural examination of reprocessed
      paraffin-embedded tissues.

PMID- 10879929
TI  - Bacterial cholecystitis with cardiac and pulmonary dissemination in a blue-naped
      mousebird (Urocolius macrourus).
AB  - A blue-naped mousebird (Urocolius macrourus) was diagnosed by gross necropsy and
      histopathology as having a chronic, fibrosing bacterial cholecystitis. Acute,
      severe, necrotizing pneumonia and myocarditis also were present with
      intralesional gram-negative bacteria. The bacteria within the lungs and heart
      were suspected to have spread from the biliary tract because of the pattern of
      distribution and similar gram-staining characteristics. Enterobacter sp. and
      Escherichia coli were cultured from the pulmonary lesions. Cloacal cultures in
      clinically normal blue-naped mousebirds and speckled mousebirds (Colius striatus)
      yielded both Enterobacter sp. and E. coli. We hypothesize a pathogenesis in this
      bird consisting of biliary stasis of unknown etiology and eventual infection of
      the biliary tract by the normal gram-negative gastrointestinal flora. Death was
      believed to be a result of cardiac and respiratory dysfunction secondary to the
      bacterial dissemination from the biliary tree and endotoxemia.

PMID- 10879931
TI  - Severe leukopenia and liver necrosis in young African grey parrots (Psittacus
      erithacus erithacus) infected with psittacine circovirus.
AB  - This paper describes the signs, clinical pathology, and postmortem findings in 14
      young African grey parrots (Psittacus erithacus erithacus) that were naturally
      infected with psittacine beak and feather disease (PBFD) virus (psittacine
      circovirus). All but two of the parrots had severe leukopenia at clinical
      presentation. Two other parrots also had severe anemia. All birds died within 3
      wk after presentation. Postmortem examination documented liver necrosis in 11 of
      14 birds and secondary bacterial or fungal infections in 9 of 14 birds. Tests for
      Chlamydia psittaci, polyomavirus, and Salmonella sp. were negative. PBFD viral
      infection could be demonstrated in all birds by polymerase chain reaction.
      Supporting evidence of PBFD viral infection was gathered by histologic
      examination of the bursa of Fabricius, electron microscopy, and DNA in situ
      hybridization. Electron microscopic examination of both the bursa of Fabricius
      and liver revealed virus particles resembling circovirus. DNA in situ
      hybridization of six liver tissue samples confirmed the presence of PBFD virus
      and excluded the presence of avian polyomavirus. Our findings suggest that a
      specific presentation of peracute PBFD viral infection, characterized by severe
      leukopenia, anemia, or pancytopenia and liver necrosis in the absence of feather
      and beak abnormalities, may occur in young African grey parrots.

PMID- 10879932
TI  - Urinary tract cryptosporidiosis in commercial laying hens.
AB  - Formalin-fixed kidney tissues from adult egg-laying chickens in two houses of an
      egg-production complex in the upper Midwest were submitted to Iowa State
      University for histopathologic examination. An increased incidence of visceral
      gout, average daily mortality 1%-2% higher than expected, and egg production
      within normal limits were observed in both houses. Numerous developing stages of
      Cryptosporidium were observed on the apical surface of epithelial cells lining
      renal collecting tubules and ureters. Scanning and transmission electron
      microscopy were used to visualize colonization of cryptosporidia, disruption of
      microvilli, and exfoliation of parasitized epithelial cells. Lymphoplasmacytic
      infiltration in the wall of ureters and hyperplasia of parasitized epithelial
      cells resulted in partial obstruction of ureters, which may have induced visceral
      gout in affected hens. This is the first report of urinary tract
      cryptosporidiosis occurring in adult hens in a modern commercial egg-production
      facility.

PMID- 10879933
TI  - Group B streptococcal infection early onset disease controversies in prevention
      guidelines, and management strategies for the neonate.
AB  - Group B streptococcus (GBS) has been a major pathogen that is particularly
      devastating to the newborn for more than two decades. Initial guidelines were
      promoted by the AAP in 1992 to help deal with this organism, but these
      recommendations were poorly accepted and not widely used. In 1996-1997 the AAP,
      CDC, and ACOG created new guidelines for the management of the mother and infant
      at risk for GBS. Though usually in agreement, these three sets of recommendations
      still have some differences that may be confusing to the pediatrician. This paper
      looks at the acquisition, intrapartum treatment, and postnatal management of GBS,
      along with some of the controversies associated with the management of this
      disease.

PMID- 10879934
TI  - Current options in the management of apnea of prematurity.
AB  - Apnea of prematurity (AOP) is a common problem that affects premature infants
      and, to a lesser degree, term infants. Apnea of prematurity appears to be due to
      immaturity of the infant's neurologic and respiratory systems. Apnea of
      prematurity is a diagnosis of exclusion that can be made only when other possible
      infectious, cardiologic, physiologic, and metabolic causes of apnea have been
      ruled out. The fundamental principles for managing apnea of prematurity include
      monitoring the infant closely while instituting supportive care measures such as
      tactile stimulation, continuous positive airway pressure, or mechanical
      ventilation. When necessary, pharmacologic therapy may be used to stimulate
      breathing. The first-line agents of choice for the management of AOP are the
      methylxanthines. And, for second-line therapy, a switch to a different class of
      agent, such as the respiratory stimulant doxapram, is an option. Of the
      methylxanthines, theophylline is the most extensively used. However, a review of
      the literature suggests that caffeine citrate may be the agent of choice for AOP.
      Comparative clinical studies have demonstrated that caffeine is at least as
      effective as theophylline, has a longer half-life, is associated with fewer
      adverse events, and, in addition, has a greater ease of administration. Caffeine
      stimulates the respiratory and central nervous systems more effectively and
      penetrates into the cerebrospinal fluid more readily than theophylline. In
      addition, because of stable plasma levels, caffeine has a wide therapeutic margin
      and few side effects. In contrast, theophylline plasma levels may fluctuate
      widely, which necessitates frequent monitoring and has a higher incidence of
      adverse events than caffeine. Before the FDA approval of caffeine citrate
      (Cafcit) for administration either intravenously and/or orally, caffeine
      preparations were "homemade." A few studies suggest that use of pharmacotherapy
      to treat AOP is not generally associated with long-term sequelae, although more
      data are needed before this can be definitively concluded.

PMID- 10879935
TI  - Factors associated with medication self-administration in children with asthma.
AB  - This study investigated factors associated with early self-administration of
      inhaled asthma medications by minority children. Specifically, the study
      evaluated: (1) the reasons parents allow early administration of inhaled
      medications, (2) childhood activities associated with early medication
      administration, (3) parent's perception of the child's ability to use a metered
      dose inhaler (MDI), (4) the child's actual ability to use an MDI, and (5)
      concordance/discordance between physician-parent reports and parent-child reports
      of asthma medications. Study results indicated that 93% of the children were
      taking inhaled asthma medications without adult supervision. Early self
      administration of asthma medications was related to the parent's employment
      status and the performance of other childhood behaviors such as completion of
      homework independently and crossing the street alone. Only 7% of the children had
      effective MDI skills, but 60% of the parents rated their child's MDI skills as
      excellent. Twenty percent, 67%, and 50%, respectively, of the parents' reports of
      beta-agonists, daily inhaled steroids, and cromolyn were discordant with the
      physician's actual prescriptions. Sixty-two percent, 57%, and 79%, respectively,
      of the children's reports for inhaled beta-agonists, daily inhaled steroids, and
      cromolyn were discordant with their parents' reports. Implications for
      anticipatory guidance, future educational strategies, and supervision of MDI
      technique are provided.

PMID- 10879936
TI  - Technical skills in chronically ill children.

PMID- 10879937
TI  - Blood glucose monitoring skills in children with Type I diabetes.
AB  - While blood glucose monitoring has become increasingly important in diabetes
      care, studies have yet to address the accuracy of youngsters' performance of
      blood glucose testing with current reflectance meters. The present study examined
      testing skills and predictors of accurate testing skills in a sample of 7-14-year
      old children attending a summer camp for youth with diabetes (n=266). A 15-item
      behavior observational skill test was used to assess accuracy of blood glucose
      monitoring skills with reflectance meters. Accurate performance of individual
      skills ranged between 14.6% and 99.6% for the sample. However, a number of
      children made critical errors (errors that were likely to lead to inaccurate
      blood glucose testing results). When duration of diabetes and metabolic control
      were controlled, female gender, older age, experience with a particular meter,
      and absence of hypoglycemia at the time of testing were positively associated
      with accurate skill performance. Findings suggest that younger children, children
      using a new blood glucose testing meter, and children suspected of having
      hypoglycemia should be supervised and observed when testing. Although all young
      children should be supervised when blood glucose testing, boys may need closer
      supervision until an older age than girls. This study underscores the need for
      health care providers to periodically observe children's blood glucose monitoring
      techniques to assure accurate testing habits and to correct problematic testing
      behaviors.

PMID- 10879938
TI  - Effectiveness of treatments for nocturnal enuresis in a heterogeneous population.
AB  - The objective of this study was to determine the effectiveness of various
      treatments for nocturnal enuresis in a large, diverse population of children. A
      retrospective cohort review of patients with nocturnal enuresis was undertaken.
      All patients selected treatment after a single visit that included a history,
      examination, and demonstration of treatments. Families were contacted 1 year
      later to determine what treatment they chose and whether their child still wet.
      Families primarily chose an alarm (31%), followed by desmopressin acetate (22%)
      and oxybutynin (9%). Some preferred no treatment (23%). Fifty-six percent of
      patients using the alarm were completely dry compared to 18% using desmopressin
      acetate (p<0.0001), 16% using oxybutynin, and 28% receiving no treatment. In a
      heterogeneous population 1 year after a single visit, children whose parents
      chose the nocturnal enuresis alarm were most likely to be completely dry.

PMID- 10879939
TI  - Brain abscess presenting as a febrile seizure.

PMID- 10879940
TI  - Crohn's disease presenting as chronic constipation: a case report.

PMID- 10879941
TI  - Intramural hematoma of the descending colon after blunt abdominal trauma.

PMID- 10879942
TI  - Adolescent girls' and boys' preferences for provider gender and confidentiality
      in their health care.

PMID- 10879943
TI  - Middle school students' sources of acquiring cigarettes and requests for proof of
      age.

PMID- 10879944
TI  - Incident Chlamydia trachomatis infections among inner-city adolescent females.

PMID- 10879945
TI  - The function of the medial superior olive in small mammals: temporal receptive
      fields in auditory analysis.
AB  - Traditionally, the medial superior olive, a mammalian auditory brainstem
      structure, is considered to encode interaural time differences, the main cue for
      localizing low-frequency sounds. Detection of binaural excitatory and inhibitory
      inputs are considered as an underlying mechanism. Most small mammals, however,
      hear high frequencies well beyond 50 kHz and have small interaural distances.
      Therefore, they can not use interaural time differences for sound localization
      and yet possess a medial superior olive. Physiological studies in bats revealed
      that medial superior olive cells show similar interaural time difference coding
      as in larger mammals tuned to low-frequency hearing. Their interaural time
      difference sensitivity, however, is far too coarse to serve in sound
      localization. Thus, interaural time difference sensitivity in medial superior
      olive of small mammals is an epiphenomenon. We propose that the original function
      of the medial superior olive is a binaural cooperation causing facilitation due
      to binaural excitation. Lagging inhibitory inputs, however, suppress
      reverberations and echoes from the acoustic background. Thereby, generation of
      antagonistically organized temporal fields is the basic and original function of
      the mammalian medial superior olive. Only later in evolution with the advent of
      larger mammals did interaural distances, and hence interaural time differences,
      became large enough to be used as cues for sound localization of low-frequency
      stimuli.

PMID- 10879946
TI  - Pupillary dilation response as an indicator of auditory discrimination in the
      barn owl.
AB  - The pupil of an awake, untrained, head-restrained barn owl was found to dilate in
      response to sounds with a latency of about 25 ms. The magnitude of the dilation
      scaled with signal-to-noise ratio. The dilation response habituated when a sound
      was repeated, but recovered when stimulus frequency or location was changed. The
      magnitude of the recovered response was related to the degree to which
      habituating and novel stimuli differed and was therefore exploited to measure
      frequency and spatial discrimination. Frequency discrimination was examined by
      habituating the response to a reference tone at 3 kHz or 6 kHz and determining
      the minimum change in frequency required to induce recovery. We observed
      frequency discrimination of 125 Hz at 3 kHz and 250 Hz at 6 kHz--values
      comparable to those reported by others using an operant task. Spatial
      discrimination was assessed by habituating the response to a stimulus from one
      location and determining the minimum horizontal speaker separation required for
      recovery. This yielded the first measure of the minimum audible angle in the barn
      owl: 3 degrees for broadband noise and 4.5 degrees for narrowband noise. The
      acoustically evoked pupillary dilation is thus a promising indicator of auditory
      discrimination requiring neither training nor aversive stimuli.

PMID- 10879948
TI  - Relating middle-ear acoustic performance to body size in the cat family:
      measurements and models.
AB  - Is the acoustic performance of the mammalian middle ear dependent on body size?
      We focus on the cat family, because of its qualitatively uniform (and
      distinctive) middle-ear structure, large size range, and the extensive data
      available from domestic cats which provide a framework for relating middle-ear
      acoustics to structure. We report measurements of acoustic admittance in 17 live
      adult ears of 11 exotic species, ranging in size from sand cat (3 kg) to tiger
      (180 kg). For low frequencies, the middle-ear response is compliant for all
      species and generally increases with size. The compliance of the middle-ear air
      space increases with size, but the compliance of the tympanic membrane and
      ossicular chain is not correlated with size. Structure-based rules are developed
      to represent some features of middle-ear performance: (1) low-frequency
      sensitivity increases with size; and (2) the frequency of a prominent notch in
      admittance decreases with size. Although some species deviate from the rules, the
      data generally support the idea that in larger felids the middle-ear response is
      shifted to lower frequencies. Thus, in the cat family, body size partly describes
      variations in auditory features. More speculatively, ethological pressures which
      might influence hearing performance are discussed.

PMID- 10879947
TI  - Variability in the role of the gasbladder in fish audition.
AB  - The teleost gasbladder is believed to aid in fish audition by transferring
      pressure components of incoming sound to the inner ears. This idea is primarily
      based on both anatomical observations of the mechanical connection between the
      gasbladder and the ear, followed by physiological experiments by various
      researchers. The gasbladder movement has been modeled mathematically as a
      pulsating bubble. This study is extending the previous work on fish with a
      physical coupling of the gasbladder and ear by investigating hearing in two
      species (the blue gourami Trichogaster trichopterus, and the oyster toadfish
      Opsanus tau) without a mechanical linkage. An otophysan specialist (the goldfish
      Carassius auratus) with mechanical coupling, is used as the control. Audiograms
      were obtained with acoustically evoked potentials (e.g., auditory brainstem
      response) from intact fish and from the same individuals with their gasbladders
      deflated. In blue gourami and oyster toadfish, removal of gas did not
      significantly change thresholds, and evoked potentials had similar waveforms. In
      goldfish thresholds increased by 33-55 dB (frequency dependent) after deflation,
      and major changes in evoked potentials were observed. These results suggest that
      the gasbladder may not serve an auditory enhancement function in teleost fishes
      that lack mechanical coupling between the gasbladder and the inner ear.

PMID- 10879949
TI  - Neuronal representation of optic flow experienced by unilaterally blinded flies
      on their mean walking trajectories.
AB  - Asymmetries in the optic flow on both eyes may indicate an unintended turn of an
      animal and evoke compensatory optomotor responses. On a straight path in an
      evenly structured environment, the optic flow on both eyes is balanced
      corresponding to a state of optomotor equilibrium. When one eye is occluded an
      optomotor equilibrium is expected to be reached on a curved path provided that
      the translatory optic flow component is cancelled by a superimposed rotation.
      This hypothesis is tested by analysing how the HSE cell, a constituent element of
      the fly's optomotor system, represents optic flow in behavioural situations. The
      optic flow as seen on the average trajectory of freely walking monocular flies is
      reconstructed. This optic flow is used as stimulus of the HSE cell in
      electrophysiological experiments and as input of a model of the fly's optomotor
      system. The responses of the HSE cell and of the model fluctuate around the
      resting potential. On average, they are much smaller than the responses evoked by
      optic flow experienced on a straight path. These results corroborate the
      hypothesis that the mean trajectory of monocular flies corresponds to a path of
      optomotor equilibrium.

PMID- 10879950
TI  - Mechanics of the inner ear of the bullfrog (Rana catesbeiana): the contact
      membranes and the periotic canal.
AB  - The frog inner ear consists of a complex of fluid-filled membranous sacs and
      canals containing eight distinct clusters of sensory hair cells. In this study we
      attempt to delineate the potential pathways for acoustic energy flow toward two
      of these clusters located within the amphibian papilla and the basilar papilla.
      Detailed morphological measurements of the periotic canal based on internal casts
      of the inner ear in the bullfrog (Rana catesbeiana) revealed that it is divided
      into a wide, tapered section and a narrower section comprised of two branches one
      short and blind projecting into the endolymphatic space and another longer,
      terminating in the round window. Additionally, we used laser Doppler velocimetry
      to record the velocity responses of the contact membranes of the amphibian
      papilla and basilar papilla. We found that the acoustic energy flow through these
      two structures is frequency dependent such that the amphibian papilla contact
      membrane displays a peak velocity amplitude at frequencies less than 500 Hz,
      whereas the basilar papilla contact membrane velocity response exhibits a maximum
      above 1,100 Hz. Our data advocate a mechanical substrate underlying the frequency
      segregation in the auditory nerve fibers innervating the amphibian papilla and
      the basilar papilla.

PMID- 10879951
TI  - A model for energy flow in the inner ear of the bullfrog (Rana catesbeiana).
AB  - We present a quantitative mathematical model that represents the main features of
      the bullfrog inner ear. Calculated responses based on this model predict the
      observed frequency separation between the amphibian papilla and basilar papilla
      responses. The origin of this separation can be traced to the effect of the
      contact membranes on the impedance of the respective paths. Additionally, we
      calculated the input impedance of the periotic canal and showed that at low
      frequencies it acts as a bypass for most of the energy entering the ear, shunting
      it away from the amphibian-basilar papilla complex. As this shunting decreases
      with increasing frequency, we propose that the periotic canal functions as a
      protection mechanism to prevent overload of the amphibian papilla and basilar
      papilla during ventilation and for quasi-static pressure equalization. Our model
      explains the main features of the empirical data obtained from direct measurement
      of the amphibian papilla and basilar papilla contact membranes reported in an
      accompanying paper (this issue).

PMID- 10879952
TI  - Light-dependent repetitive Ca2+ spikes induced by extracellular application of
      neomycin in honeybee drone photoreceptors.
AB  - Photoreceptor cells of the honeybee drone fire, in the presence of the
      polycationic aminoglycoside neomycin, repetitive slow spike-like potentials
      superimposed on the receptor potential plateau phase. We have used conventional
      intracellular recordings and microfluorometric intracellular Ca2+ measurements to
      characterize these spike potentials. We have shown that the spike frequency
      increases in a light-intensity-dependent manner. The spikes are fired only when
      light stimuli depolarize the cell from a resting potential of -50 to -60 mV to at
      least -40 to -45 mV; they are tetrodotoxin insensitive and blocked by the Ca2+
      channel blockers Ni2+, Cd2+, omega-agatoxin TK, verapamil and methoxyverapamil.
      Depolarization of the photoreceptors with high extracellular K+ in the presence
      of neomycin in darkness does not generate spikes. Small intracellular Ca2+
      oscillations superimposed on the plateau phase of the light-induced increase in
      intracellular free Ca2+ concentration have a similar temporal pattern as the
      spike-like potentials. We conclude that the spike-like potentials require
      stimulation by light and are generated by voltage-dependent Ca2+ channels
      localized on the soma of the photoreceptors, distal to the basal lamina.

PMID- 10879953
TI  - A decade of capillary electrophoresis.
AB  - Since the introduction of the first commercial capillary electrophoresis (CE)
      instrument a decade ago, CE applications have become widespread. Today, CE is a
      versatile analytical technique which is successfully used for the separation of
      small ions, neutral molecules, and large biomolecules and for the study of
      physicochemical parameters. It is being utilized in widely different fields, such
      as analytical chemistry, forensic chemistry, clinical chemistry, organic
      chemistry, natural products, pharmaceutical industry, chiral separations,
      molecular biology, and others. It is not only used as a separation technique but
      to answer physicochemical questions. In this review, we will discuss different
      modes of CE such as capillary zone electrophoresis, micellar electrokinetic
      chromatography, capillary gel electrophoresis, capillary isoelectric focusing,
      and capillary electrochromatography, and will comment on the future direction of
      CE, including array capillary electrophoresis and array microchip separations.

PMID- 10879954
TI  - Determination of enantiomeric excess by capillary electrophoresis.
AB  - Capillary electrophoresis (CE) is becoming an established method for the
      determination of chiral trace impurities. This paper provides an overview of the
      state of the art of CE for such determinations. Detection limits of 0.1% impurity
      is widely accepted as a minimum requirement for chiral trace impurity
      determinations. This can be relatively easily achieved with CE. However,
      determination of lower concentrations requires careful optimization of the
      separation system. Four factors that are of particular significance for trace
      enantiomeric determinations: resolution, limit of detection, linear range and
      type of detection, are discussed. Further, the advantages and disadvantages of
      derivatization in this context are treated as well as the separation approach,
      ie., direct chiral separation or separation after the formation of diastereomers.
      It is concluded that the limit of impurity detection can be about 0.05% when UV
      detection is employed. Using laser-induced fluorescence detection, a quantitative
      determination at the 0.005% level is often possible.

PMID- 10879955
TI  - Enantiospecific analysis by capillary electrophoresis: applications in drug
      metabolism and pharmacokinetics.
AB  - Enantiospecific analysis has an important role in drug metabolism and
      pharmacokinetic investigations and its now no longer acceptable to determine
      total drug, or metabolite, concentrations following the administration of a
      racemate. Inspite of the fact that capillary electrophoresis (CE) has become an
      essential technique in pharmaceutical and enantiospecific analysis, the
      chromatographic methodologies remain the most commonly used approach for the
      determination of the enantiomeric composition of drugs in biological fluids. The
      application of CE to bioanalysis has been slow, which is in part associated with
      the complexity of biological matrices together with the relatively poor
      concentration limits of detection achievable. However, as a result of its
      versatility, high separation efficiency, minimal sample requirements, speed of
      analysis and low consumable expense CE is likely to play an increasingly
      significant role in the area. This review present an overview of enantiospecific
      CE in bioanalysis in which the approaches to enantiomeric resolution and the
      problems associated with biological matrices are briefly discussed. The
      application of enantiospecific CE to samples of biological origin is illustrated
      using examples where the methodology has either solved an analytical problem, or
      provided a useful alternative to the currently available chromatographic methods.
      Such improvements in methodology are associated with either the high separation
      efficiency and/or microanalytical capabilities of the technique. Enantiospecific
      CE will not replace the chromatographic methodologies but does provide the
      bioanalyst with a useful addition to his armamentarium.

PMID- 10879956
TI  - Electrically driven microseparation methods for pesticides and metabolites: III.
      Capillary electrochromatography with novel silica-based stationary phases having
      a surface-bound surfactant moiety.
AB  - A silica-based stationary phase with surface bound silylpropyl trialkylammonium
      functions was introduced and evaluated in the capillary electrochromatography of
      alkylbenzenes and pesticides. This stationary phase is referred to as
      octadecyldimethyl(3-trimethoxysilylpropyl) ammonium-silica (ODAS) and has
      quaternary amine functions that generate an anodic electroosmotic flow (EOF) and
      octadecyl functions that are responsible for solute retention by a reversed-phase
      chromatography mechanism. The ODAS stationary phase was characterized over a wide
      range of elution conditions in term of EOF and retention behavior of alkylbenzene
      homologous series. The ODAS stationary phase proved useful in the separation of
      pesticides as well as in the on-column preconcentration of dilute pesticide
      samples, thus permitting the detection of solution at 7 x 10(-7) M using a UV
      detector.

PMID- 10879957
TI  - Separation of closely related peptide substrates of human proteinases by micellar
      electrokinetic chromatography with anionic and nonionic surfactants.
AB  - In order to use micellar electrokinetic chromatography to determine the
      proteolytic activity of different proteinases simultaneously present in
      physiological fluids, the technique must be able to separate mixtures of
      substrates with closely related structures. In an attempt to determine the best
      electrophoretic conditions for resolving six p-nitroanilide peptides used as
      synthetic substrates of the elastolytic enzymes (human neutrophil elastase,
      cathepsin G, Pseudomonas aeruginosa elastase) most commonly involved in pulmonary
      diseases, we investigated the efficiency of ionic and nonionic surfactants in
      achieving the separation of this complex mixture. The results presented here show
      that, of all the electrophoretic systems tested, 30 mM sodium tetraborate, pH
      9.3, containing 25 mM Brij 35 as micellar agent offered the best performance; the
      separation efficiency of peptides is greater than that obtained with other
      reagents and all peaks are baseline resolved and unambiguously identifiable.
      Analysis of the micelle-solute interaction with the surfactants investigated
      allowed better definition of the mechanism involved in the distribution of these
      peptides to the micelles and identification of some structural features that
      determined the magnitude of the micelle peptide complex formation.

PMID- 10879958
TI  - Separation of naphthalene-2,3-dicarboxaldehyde-derivatized-substance P and its
      metabolites by micellar electrokinetic chromatography.
AB  - This paper describes the development of analytical methodology for the separation
      of naphthalene-2,3-dicarboxaldehyde (NDA)-derivatized substance P (CBI-SP) and
      five lysine-containing metabolites by micellar electrokinetic chromatography
      (MEKC). The effect of surfactant composition and organic modifiers on the
      separation was investigated. The final separation buffer consisted of 80 mM
      sodium cholate in 50 mM N-tris (hydroxymethyl)methyl-2-aminoethanesulfonic acid
      (TES), pH 7. All six lysine-containing peptides were separated under these
      conditions.

PMID- 10879959
TI  - Dual-opposite injection electrokinetic chromatography for the unbiased,
      simultaneous separation of cationic and anionic compounds.
AB  - The concept of dual opposite injection in capillary electrophoresis (DOI-CE) for
      the simultaneous separation, under conditions of suppressed electroosmotic flow,
      of anionic and cationic compounds with no bias in resolution and analysis time,
      is extended to a higher pH range in a zone electrophoresis mode (DOI-CZE). A new
      DOI-CE separation mode based on electrokinetic chromatography is also introduced
      (DOI-EKC). Whereas conventional CZE and DOI-CZE are limited to the separation of
      charged compounds with different electrophoretic mobilities, DOI-EKC is shown to
      be capable of separating compounds with the same or similar electrophoretic
      mobilities. In contrast to conventional EKC with charged pseudostationary phases
      that often interact too strongly with analytes of opposite charge, the neutral
      pseudostationary phases appropriate for DOI-EKC are simultaneously compatible
      with anionic and cationic compounds. This work describes two buffer additives
      that dynamically suppress electroosmotic flow (EOF) at a higher pH (6.5) than in
      a previous study (4.4), thus allowing DOI-CZE of several pharmaceutical bases and
      weakly acidic positional isomers. Several DOI-EKC systems based on nonionic (10
      lauryl ether, Brij 35) or zwitterionic (SB-12, CAS U) micelles, or nonionic
      vesicles (Brij 30) are examined using a six-component test mixture that is
      difficult to separate by CZE or DOI-CZE. The effect of electromigration
      dispersion on peak shape and efficiency, and the effect of surfactant
      concentration on retention, selectivity, and efficiency are described.

PMID- 10879960
TI  - Use of single-isomer, multiply charge chiral resolving agents for the continuous,
      preparative-scale electrophoretic separation of enantiomers based on the
      principle of equal-but-opposite analyte mobilities.
AB  - A novel approach to continuous, preparative-scale electrophoretic enantiomer
      separations has been developed based on the observation that stable, equal-but
      opposite effective mobilities can be created for the enantiomers of a single
      charged analyte by complexing them with a single-isomer, multiply charged
      resolving agent, provided that the charge of the resolving agent is opposite in
      sign to that of the uncomplexed analyte enantiomers. When such an analyte
      resolving agent system is fed into a continuous, free-flow electrophoretic
      apparatus, stable, steady-state operating conditions can be established which
      permit the continuous feeding of the racemic analyte and the collection of pure
      enantiomers at the opposite sides of the feed stream. This concept is
      demonstrated via the separation of the enantiomers of terbutaline using heptakis
      6-sulfato beta-cyclodextrin as resolving agent, affording production rates as
      high as 2.8 mg/h in the general-purpose, continuous free-flow electrophoretic
      system, the Octopus.

PMID- 10879961
TI  - Experimental verification of a predicted, hitherto unseen separation selectivity
      pattern in the nonaqueous capillary electrophoretic separation of weak base
      enantiomers by octakis (2,3-diacetyl-6-sulfato)-gamma-cyclodextrin.
AB  - The capillary electrophoretic separation of cationic enantiomers with single
      isomer multivalent anionic resolving agents was reexamined with the help of the
      charged resolving agent migration model. Three general model parameters were
      identified that influence the shape of the separation selectivity and enantiomer
      mobility difference curves: parameter b, the binding selectivity (K(RCD)/K(SCD)),
      parameter s, the size selectivity (mu0(RCD)/mu0(SCD)), and parameter a, the
      complexation-induced alteration of the analyte's mobility (mu0(RCD)/mu0). In
      addition to the previously observed discontinuity in separation selectivity that
      occurs as mu(eff) of the less mobile enantiomer changes from cationic to anionic,
      a new feature, a separation selectivity maximum was predicted to occur in the
      resolving agent concentration range where both enantiomers migrate cationically
      provided that (i) K(RCD)/K(SCD) <1 and mu0(RCD)/mu0(SCD) >1 and
      (K(RCD)mu0(RCD))/(K(SCD)mu0(SCD)) > 1, or (ii) K(RCD)/K(SCD) >1 and
      mu0(RCD)/mu0(SCD) <1 and (K(RCD)mu0(RCD))/(K(SCD)mu0(SCD)) <1. This hitherto
      unseen separation selectivity pattern was experimentally verified during the
      nonaqueous capillary electrophoretic separation of the enantiomers of four weak
      base analytes in acidic methanol background electrolytes with octakis(2,3
      diacetyl-6-sulfato)-gamma-cyclodextrin (ODAS-gammaCD) as resolving agent.

PMID- 10879962
TI  - Capillary electrophoretic separation of binaphthyl enantiomers with two polymeric
      chiral surfactants: 1H-nuclear magnetic resonance and fluorescence spectroscopy
      study.
AB  - The use of the water-soluble polymeric chiral surfactants (PCS), sodium N
      undecanoyl-L-valinate (poly-L-SUV) and sodium undecanoyl-L-isoleucinate (poly-L
      SUI) as buffer additives in electrokinetic chromatography (EKC) afforded the
      separation of racemic mixtures of 2,2'-dihydroxy-1,1'-binaphthyl (BOH) and 1,1'
      binaphthyl-2,2'-diyl hydrogen phosphate (BNP). The apparent binding constants of
      the PCS to the enantiomers of BNP and BOH were obtained through 1H-nuclear
      magnetic resonance (1H-NMR) titrations and fluorescence spectroscopy,
      respectively. The 1H-NMR titration studies show that the BNP enantiomers are
      localized in the hydrophobic micellar pockets of PCS and form complexes of a 1:1
      stoichiometry. The binding constants of PCS of BOH were determined from a Benesi
      Hildebrand treatment of the fluorescence data. The EKC data corroborate those of
      the binding constants, supporting the formation of inclusion complexes. A model
      rationalizing the chiral discrimination of the enantiomers of BNP is proposed
      based on the intermolecular interactions observed in 1H-NMR data.

PMID- 10879963
TI  - Investigation of the chiral surfactant N-dodecoxycarbonylvaline in electrokinetic
      chromatography: improvements in elution range and pH stability via mixed micelles
      and vesicles, and the hydrophobicity determination of basic pharmaceutical drugs.
AB  - The chiral surfactant dodecoxycarbonylvaline (DDCV) has proven to be an effective
      pseudostationary phase for the separation of many enantiomeric pharmaceutical
      compounds. In this study the elution range and the prediction of octanol-water
      partitioning for the DDCV micellar system was examined. Through incorporation of
      DDCV in mixed micelles and unilamellar vesicles, enhancement of the elution range
      was observed. The mixed micelles contained a second anionic surfactant, sodium
      dodecyl sulfate (SDS), while the vesicles were composed of DDCV and the cationic
      surfactant cetyltrimethylammonium bromide (CTAB). Enantioselectivity, as well as
      other chromatographic and electrophoretic parameters, were compared between the
      mixed micelles, vesicles, and DDCV micelles. The hydrophobicity of the DDCV
      system was also evaluated as a predictor of n-octanol-water partition
      coefficients for 15 beta amino alcohols. The correlation between the logarithm of
      the retention factor (log k) and log P(ow) for seven hydrophobic beta-blockers
      and eight beta-agonists were r2 = 0.964 and r2 = 0.814, respectively.

PMID- 10879964
TI  - Electrically driven microseparation methods for pesticides and metabolites: IV.
      Effects of the nature of fluorescent labels on the enantioseparation of
      pesticides and their degradation products by capillary zone electrophoresis with
      UV and laser-induced fluorescence detection.
AB  - Three different fluorescent tags, namely 5-aminonaphthalene-1-sulfonic acid
      (ANSA), 7-aminonaphthalene-1,3-disulfonic acid (ANDSA), and 8-aminonaphthalene
      1,3,6-trisulfonic acid (ANTS) were evaluated in the precolumn derivatization of
      some chiral phenoxy acid herbicides, some chiral transformation products of
      pyrethroid insecticides, and in their subsequent enantiomeric separation by
      capillary electrophoresis (CE). The electrolyte systems consisted of sodium
      phosphate buffers containing chiral surfactants such as octylglucoside (OG) or
      octylmaltoside (OM) at concentrations above the critical micellar concentration
      (CMC). Among the three different tags investigated, the ANDSA derivatives of the
      various solutes were more readily enantioseparated than the ANSA and ANTS
      derivatives. While the tagging with ANSA allowed the enantioseparation of a
      limited number of the chiral solute-ANSA derivatives investigated, the ANTS
      derivatization yielded derivatives that could not be enantioseparated. The
      polarity of the three different tags increases by increasing the number of
      sulfonic acid groups in the molecule in the following order: ANSA (one sulfonic
      acid) < ANDSA (two sulfonic acid groups) < ANTS (three sulfonic acid groups).
      This seems to indicate that the intermediate polarity of the ANDSA tag allowed
      more equitable nonpolar/polar interactions of the ANDSA-derivatized solutes with
      the OG or OM micelles, and consequently the enantioseparation of the solute-ANDSA
      derivatives. Thus, there is a solute polarity window for enantioresolution with
      alkylglycoside micelle by CE. Solutes of intermediate polarity that undergo more
      equitable nonpolar/polar interactions with the micelles exhibited chiral
      separations.

PMID- 10879965
TI  - An enantiomeric assay for the flavonoids medicarpin and vestitone using capillary
      electrophoresis.
AB  - An enantiomeric assay for the flavonoids vestitone and medicarpin from transgenic
      plant extracts was developed using capillary electrophoresis. It was found that
      no single cyclodextrin proved capable of resolving the enantiomers of both
      medicarpin and vestitone. Instead, hydroxypropyl-beta-cyclodextrin provided the
      best selectivity for the vestitones while hydroxypropyl-gamma-cyclodextrin was
      best for the medicarpins. The addition of organic modifiers improved the
      resolution of both enantiomers. Acetonitrile proved best for the vestitones and
      only methanol improved the resolution of the medicarpins. An optimization study
      of mixed hydroxypropyl-beta-cyclodextrin and hydroxypropyl-gamma-cyclodextrin
      containing electrolytes revealed that the separation of the medicarpin
      enantiomers was intolerant to the presence of hydroxypropyl-beta-cyclodextrin.
      Our optimized running electrolyte was composed of 2 mM hydroxypropyl-beta
      cyclodextrin, 20 mM hydroxypropyl-gamma-cyclodextrin, and 25 mM borate at pH 10.0
      with 10% v/v methanol. This system provided a resolution of 1.47 and 1.80 for the
      medicarpin and vestitone enantiomers, respectively. This analysis was completed
      in 12 min. This separation provided a rapid screen to determine the enantiomeric
      purity of key flavonoids biosynthesized by transgenic legumes.

PMID- 10879966
TI  - Rapid and sensitive genotyping of dopamine D4 receptor tandem repeats by
      automated ultrathin-layer gel electrophoresis.
AB  - Prior studies have revealed possible association between the presence of a seven
      repeat of the 48 bp variable number tandem repeat polymorphism of the human
      dopamine D4 receptor gene (DRD4) and some normal and pathological human traits,
      such as novelty seeking, hyperactivity disorders, and substance abuse. Some
      reports supported this finding whereas others did not. Incorrect genotyping could
      be one of the reasons for these controversial results, and might originate from
      preferential amplification of shorter polymerase chain reaction (PCR) products,
      resulting in the so-called allele dropout. In this paper we optimized the
      conditions for simultaneous amplification of shorter and longer amplicons of the
      48 bp repeat region of the DRD4 gene in order to avoid the loss of the longer
      allele and consequent incorrect genotyping, using very low DNA template
      concentrations and partial replacement of 2'-deoxyguanosine-5'-triphosphate
      (dGTP) by 2'-deoxyinosine-5'-triphosphate (dITP). The optimized PCR method in
      combination with high throughput automated ultrathin-layer gel electrophoresis
      was suitable for rapid genotyping from less than a nanogram DNA using noninvasive
      sampling (buccal epithelial cells). All detected genotypes are presented,
      including such rear heterozygotes as the 2 x and 8 x 48 bp repeats in the same
      sample, showing the reliability of our novel detection method of longer alleles
      in the presence of shorter alleles.

PMID- 10879967
TI  - Solid-state UV laser-induced fluorescence detection in capillary electrophoresis.
AB  - Two solid-state UV lasers were applied to the laser-induced fluorescence (LIF)
      detection of various groups of compounds after separation by capillary
      electrophoresis. These lasers are thermoelectric-cooled, highly compact, and
      inexpensive. Such lasers provide few mW of quasi-continuous wave (CW) power which
      are sufficient and stable for LIF detection. Native fluorescence detection of
      tryptophan-containing proteins and peptides and related indoles was achieved at
      the nM level with the laser operating at 266 nm. Detection of fluorescamine
      labeled amino acids and peptides was also possible at the nM level with the laser
      operating at 355 nm. Amino acids at a concentration as low as 10 ng/mL could be
      labeled with fluorescamine. Solid-state UV-LIF detection of the tryptic digest of
      cytochrome c after fluorescamine derivatization was demonstrated.

PMID- 10879968
TI  - Optimization of the conditions for biuret complex formation for the determination
      of peptides by capillary electrophoresis with ultraviolet detection.
AB  - Capillary electrophoresis with UV detection was utilized to optimize copper
      complexation conditions for the analysis of neuropeptides. Complexation was
      confirmed by monitoring the response at a visible wavelength. Four complexation
      strategies were used to compare the UV response of native peptides and their
      respective copper complexes. All four strategies resulted in complete
      complexation, but on-capillary complexation provided significant advantages over
      precapillary and pre-/on-capillary. An increase in UV absorbance along with peak
      stacking resulted in a significantly greater response using the on-capillary
      technique. Also, on-capillary complexation does not require dilution of the
      sample. The effects of temperature and copper concentration were also
      investigated. The utility of this method for the separation of an enkephalin
      peptide mixture is presented.

PMID- 10879969
TI  - Plasma total homocysteine and other thiols analyzed by capillary
      electrophoresis/laser-induced fluorescence detection: comparison with two other
      methods.
AB  - We present a new analytical method for thiol quantification in plasma, based on
      the use of capillary electrophoresis (CE) and laser-induced fluorescence (LIF) to
      analyze 6-iodoacetamidofluorescein derivatives. Quantitative results of
      homocysteine, glutathione, cysteinylglycine, and cystationine are presented. A
      comparison of the quantitation of homocysteine in plasma, using high performance
      liquid chromatography/fluorescence detection and fluorescence polarization
      immunoassay is proposed. The results indicate that these techniques for plasma
      total homocysteine (tHcy) determination can be used interchangeably. The major
      advantage of CE-LIF is that it can quantitate the thiols in one run while keeping
      the price of consumables reasonable.

PMID- 10879970
TI  - Detection of a urinary biomaker for oxidative DNA damage 8-hydroxydeoxyguanosine
      by capillary electrophoresis with electrochemical detection.
AB  - 8-Hydroxydeoxyguanosine (8-OHdG) is present in urine as a result of oxidative DNA
      damage associated with age-related diseases such as cancer. In this report a
      method is presented for the detection of 8-OHdG in human morning urine utilizing
      capillary electrophoresis with electrochemical detection (CEEC). The limit of
      detection for a aqueous standard of 8-OHdG is 50 nM (signal to noise ratio S/N =
      3). A single solid-phase extraction (SPE) step with a C18 column is used for
      sample cleanup and 20-fold preconcentration of the urine before analysis by CEEC.
      Optimized conditions for analysis of extracted urine are E(app) = 0.5 V vs.
      Ag/AgCl with 20 mM sodium borate/20% MeOH v/v, pH 9, as the background
      electrolyte, and a separation voltage of 22 kV. The concentration of 8-OHdG
      varied from 6 to 86 nM with an average value of 42 +/- 26.9 nM for four healthy
      female and four healthy male subjects between the ages of 23 and 43.

PMID- 10879971
TI  - Synthesis of fluorescently labeled alkylated DNA adduct standards and separation
      by capillary electrophoresis.
AB  - DNA adducts are regarded as individual internal dosimeters for the exposure to
      chemical carcinogens. To date, the most sensitive method for DNA adduct analysis
      is the radioactive 32P-postlabeling method, which allows the detection of one
      adduct in 10(10) unmodified nucleotides in microg amounts of DNA. However, this
      technique suffers from disadvantages such as working with radioactive phosphorus
      and time-consuming chromatographic separation procedures. In addition, the
      simultaneous detection of adducts from different classes of carcinogens in a DNA
      sample is difficult. In order to overcome these drawbacks, we are developing a
      new detection method, comprising fluorescence labeling of DNA adducts, capillary
      electrophoretic (CE) separation, and on-line detection by monitoring laser
      induced fluorescence (LIF). So far, we have evaluated the separation power and
      the detection limit of CE with fluorescently labeled standard compounds such as
      unmodified nucleotides or alkylated thymidines. For this purpose, we developed a
      universal method for labeling 5'-OH-mononucleosid-3'-dicyanoethyl-phosphates with
      fluorescent dyes based on the phosphoramidite technology for DNA synthesis. The
      separation of N3-methylated, N3-, O2- and O4-butylated thymidines from the
      unmodified nucleotide within a few minutes recommends CE-LIF as a powerful method
      for DNA adduct analysis.

PMID- 10879972
TI  - Who is out there? Microbial aspects of biodiversity.

PMID- 10879973
TI  - Organization of the ribosomal operon 165-235 gene spacer region in
      representatives of Neisseria gonorrhoeae.
AB  - Ribosomal rRNA gene fragments (rDNA) encompassing part of the 16S rDNA, the 16S
      23S rDNA spacer region and part of the 23S rDNA of 229 Neisseria gonorrhoeae
      strains were enzymatically amplified using conserved primers. The fragments of
      approximately 1200 bp were subjected to restriction analysis with HinfI. This
      revealed 13 patterns (patterns I-XIII) of which patterns I (78 strains), II (32
      strains), III (38 strains) and IV (56 strains) were the most abundant, comprising
      89.1% of the strains. The obtained restriction patterns consisted of 3 to 8
      bands, ranging in size from 32 to 854 bp. The sum of the obtained bands was about
      1200 bp for patterns I, II, III, IV, V, IX, and XIII. However, for patterns VI,
      VII, VIII, X, XI and XII, the sum of the bands well exceeded the estimated size
      of approximately 1200 bp. We demonstrated that this results from sequence
      divergence in the 4 rRNA operons, present in the genome of N. gonorrhoeae, giving
      rise to patterns that are a combination of several other patterns.

PMID- 10879974
TI  - Characterization of the ribosomal rrnD operon of the cephamycin-producer
      'Nocardia lactamdurans' shows that this actinomycete belongs to the genus
      Amycolatopsis.
AB  - The cephamycin producer strain 'Nocardia lactamdurans' contains four ribosomal
      RNA (rrn) operons. One of them (rrnD) was cloned from a DNA library in the
      bifunctional cosmid pJAR4. A 2229 bp region of rrnD has been sequenced. The 'N.
      lactamdurans' rrnD operon maintains the canonical order 5'-16S-23S-5S-3'. Four of
      the consensus Gurtler-Stanisch sequences were found in the 16S rRNA gene and a
      fifth one in the sequenced 5' region of the 23S rRNA gene. The anti Shine
      Dalgarno sequence of 'N. lactamdurans' (located in the 3'-end of the 16S rRNA
      gene) was found to be 5'-CCUCCUUUCU-3' and is identical to that of
      Corynebacterium lactofermentum and Mycobacterium tuberculosis. A phylogenetic
      analysis of 'N. lactamdurans' by the neighbor-joining method using the entire 16S
      rRNA nucleotide sequence revealed that this actinomycete is closely related to
      Amlycolatopsis orientalis subsp orientalis, Amycolatopsis coloradensis,
      Amycolatopsis alba, Amycolatopsis sulphurea and other Amycolatopsis sp. but only
      distantly related to species of the genus Nocardia. The cephamycin producer 'N.
      lactamdurans' NRRL 3802 should be, therefore, classified as Amycolatopsis
      lactamdurans. The deduced secondary structure of the 16S rRNA is very similar to
      that of A. colorandensis and A. alba but different from those of species of the
      Nocardia genus supporting the incorporation of 'N. lactamdurans' into the genus
      Amycolatopsis.

PMID- 10879975
TI  - Cloning and characterization of a Bacillus thuringiensis serovar higo gene
      encoding a novel class of the delta-endotoxin protein, Cry27A, specifically
      active on the Anopheles mosquito.
AB  - A novel gene encoding a 98-kDa mosquitocidal delta-endotoxin protein, designated
      Cry27A, was cloned from a Bacillus thuringiensis serovar higo strain. The Cry27A
      protein contained the five sequence blocks of amino acids commonly conserved in
      most B. thuringiensis Cry proteins. Relatively high homologies, ranging from
      43.0% to 84.4%, existed between the Cry27A protein and several established
      classes of mosquitocidal Cry proteins (Cry4A, Cry10A, Cry19A, Cry19B, and Cry20A)
      in the sequence of 51 N-terminal amino acids. The complete sequence of this
      protein, however, showed low levels (<40%) of amino acid identity to those of the
      known Cry proteins. Although the expression level of the cry27A gene was low in
      the transformants under the control of its own promoter, the use of the cyt1A
      promoter resulted in high-level expression of the gene, leading to the formation
      of inclusions. The expressed Cry27A protein showed larvicidal activity highly
      specific for Anopheles stephensi, but lacked the toxicity against Culex pipiens
      molestus and Aedes aegypti. The results suggest that the Cry27A protein is
      responsible for the Anopheles-preferential toxicity of the B. thuringiensis
      serovar higo strain.

PMID- 10879976
TI  - Salt adaptation in pseudomonads: characterization of glucosylglycerol
      synthesizing isolates from brackish coastal waters and the rhizosphere.
AB  - The compatible solute glucosylglycerol (GG) is widespread among cyanobacteria,
      but, until now, has been reported for only two species of heterotrophic bacteria.
      About 120 bacterial isolates from coastal regions of the Baltic Sea were screened
      by HPLC for their ability to synthesize GG. Positive isolates (26) were grouped
      by SDS-PAGE of whole-cell proteins and representative strains of each group were
      investigated by sequencing their 16S rRNA genes and phenotypic characterization.
      All GG-synthesizing isolates were shown to belong to the genus Pseudomonas (sensu
      stricto) and were assigned to 4 distinct groups, although none of the GG
      synthesizing isolates could be unambiguously assigned to described species. The
      identity of GG was verified by 13C NMR analysis and enzymatic digestion with
      alpha- and beta-glucosidases. Besides GG, salt adapted cultures of the aquatic
      isolates accumulated the dipeptide N-acetylglutaminylglutamine amide (NAGGN) and
      glutamate. The accumulation of noncharged compatible solutes was also tested in
      previously identified pseudomonads isolated from the rhizosphere of oilseed rape
      and potato. The majority of these strains were fluorescent species of the genus
      Pseudomonas and accumulated trehalose and NAGGN when grown under salt stress
      conditions. However, rhizosphere isolates of Stenotrophomonas maltophilia
      synthesized GG and trehalose or only trehalose in a strain-dependent manner.
      These data indicate that the ability to synthesize GG is widely distributed among
      slightly or moderately halotolerant pseudomonads.

PMID- 10879977
TI  - The effect of vitamins and amino acids on glucose uptake in aerobic chemostat
      cultures of three Saccharomyces cerevisiae strains.
AB  - In the respiro-fermentative region of aerobic chemostat cultures at steady state,
      Saccharomyces cerevisiae CBS 8066 produced high concentrations of ethanol with
      concomitant low levels of residual glucose which followed Monod kinetics. By
      contrast, very high residual glucose concentrations were observed in cultures of
      S. cerevisiae strains ATCC 4126 and NRRL Y132 at dilution rates above 60% of the
      washout dilution rate, resulting in much lower ethanol concentrations, even
      though clearly glucose-limited at lower dilution rates in the respiratory region.
      The addition of a vitamin mixture resulted in decreased residual glucose
      concentrations in respiro-fermentative cultures of all three strains, but the
      effect was much more pronounced with strains ATCC 4126 and NRRL Y132. Meso
      inositol was mainly responsible for this effect, although with strain ATCC 4126
      other vitamins as well as an amino acid mixture were also required to minimise
      the steady-state residual glucose levels. The residual glucose concentration in
      continuous culture was, therefore, greatly dependent on the growth factor
      requirements of the particular yeast strain, which apparently increased on
      increasing the dilution rate into the respiro-fermentative region. The strain
      differences with respect to growth factor requirements at high dilution rates,
      which were not evident at low dilution rates, had a profound effect on the
      kinetics of glucose assimilation in aerobic chemostat culture.

PMID- 10879978
TI  - The relationship of nitrate reducing bacteria on the basis of narH gene sequences
      and comparison of narH and 16S rDNA based phylogeny.
AB  - On the basis of available nitrate reductase gene sequences primer pairs were
      designed to specifically amplify gene stretches of the beta-subunit of the
      membrane-bound nitrate reductase (narH). Additional sequences of this gene were
      amplified and sequenced from pure cultures of reference species and new isolates.
      The distribution and phylogeny of this gene in denitrifying and nitrate-reducing
      bacteria was analysed. Comparison of phylogenetic trees based on 16S rDNA
      sequences with those based on narH sequences revealed highly similar
      relationships of both genes from most of the bacteria analysed. Since highly
      conserved functional cysteine clusters within bacterial and archaeal narH
      sequences support a linear evolution from one common progenitor a long
      evolutionary history of the respiratory membrane-bound nitrate reductase can be
      inferred from our phylogenetic data.

PMID- 10879979
TI  - Identification of Yersinia enterocolitica within the genus Yersinia.
AB  - In this report we describe a PCR strategy for the unambigous identification of
      biochemically presumptive typed Yersinia (Y.) enterocolitica. A total of 269
      isolates belonging to ten species of the genus Yersinia were investigated. In a
      first PCR only isolates classified as Y. enterocolitica (n = 113) gave rise to a
      specific amplification resulting in a sensitivity and a specificity of 100%. By
      sequencing the 269 amplicons of a second pan-Yersinia PCR spanning a distinct 16S
      rRNA gene region, 20 different sequence clusters could be identified within the
      genus. By this, Y. enterocolitica isolates of American and European origin could
      be distinguished safely and already described sequence clusters of the species Y.
      frederiksenii were confirmed. New 16S rRNA gene sequence clusters were detected
      for the species Y. frederiksenii, Y. intermedia, Y. mollaretii, Y. aldovae, Y.
      kristensenii, and Y. rohdei.

PMID- 10879980
TI  - Taxonomic significance of fucose in the class Urediniomycetes: distribution of
      fucose in cell wall and phylogeny of urediniomycetous yeasts.
AB  - The carbohydrate compositions of cell wall were determined in the strains of
      class Urediniomycetes, mainly ballistoconidium-forming yeasts and related taxa.
      The major component of cell wall was mannose, and glucose was included as the
      second component, but xylose was not detected in any strain. Out of 41 strains
      examined, 39 contained galactose, 14 contained arabinose and 12 contained
      rhamnose. As a minor component, fucose was detected in 30 strains but not in 11
      strains. A phylogenetic tree based on 18S rDNA sequences indicated that the
      fucose-lacking strains, Erythrobasidium hasegawianum, Rhodotolura aurantiaca, R.
      lactosa, R. minuta, Sakaguchia dacryoidea, Sporobolomyces coprosmae, S.
      elongatus, S. folicola, S. gracilis, S. kluyverinielii and S. oryzicola,
      constituted a distinct cluster from those strains which contained fucose. This
      cluster corresponded to one of the five subclusters, the Erythrobasidium cluster,
      in the phylogenetic tree of class Urediniomycetes. The carbohydrate composition
      of cell wall is believed to reflect the phylogenetic relationships among
      basidiomycetous fungi. The presence or absence of fucose in cell wall should be
      regarded as an important phenotypic characteristic in the taxonomy of
      basidiomycetes.

PMID- 10879981
TI  - Molecular typing demonstrates homogeneity of Saccharomyces uvarum strains and
      reveals the existence of hybrids between S. uvarum and S. cerevisiae, including
      the S. bayanus type strain CBS 380.
AB  - PCR/RFLP of the NTS2 sequence of rDNA was shown to be suitable for
      differentiating Saccharomyces sensu stricto species. We previously showed that,
      within the presently accepted S. bayanus taxon, strains formerly classified as S.
      uvarum represented a distinct subgroup (Nguyen and Gaillardin, 1997). In this
      study, we reidentified 43 more strains isolated recently from wine, cider and
      various fermentation habitats, and confirmed by karyotyping, hybridization and
      mtDNA analysis the homogeneity of strains from the S. uvarum subspecies.
      Molecular typing of nuclear and mitochondrial genomes of strains preserved in
      collections, and often originating from beer like S. pastorianusNT, revealed the
      existence of hybrids between S. uvarum and S. cerevisiae. Surprisingly, S.
      bayanusT CBS380 appeared itself to be a hybrid between S. uvarum and S.
      cerevisiae. This strain has a mitochondrial genome identical to that of S.
      uvarum, and a very similar karyotype with 13 isomorphic chromosomes, six of which
      at least hybridize strongly with S. uvarum chromosomes or with a S. uvarum
      specific sequence. However, four of the chromosome bands of S. bayanusT bear Y'
      sequences indistinguishable from those of S. cerevisiae, a feature that is not
      observed among presently isolated S. uvarum strains. Because of the hybrid nature
      of S. bayanus(T) and of the scarcity of similar hybrids among present days
      isolates, we propose to reinstate S. uvarum as a proper species among the
      Saccharomyces sensu stricto complex.

PMID- 10879982
TI  - Genetic variation among European strains of Saccharomyces paradoxus: results from
      DNA fingerprinting.
AB  - We used microsatellite fingerprinting and RAPD analysis to characterize 28 wild
      European strains of Saccharomyces paradoxus. In contrast to our results from a
      previous allozyme survey [Naumov et al. Int. J. Syst. Bacteriol. 47: 341-344
      (1997a)], these methods revealed extensive genetic variation. The RAPD primers
      5'AATCGGGCTG and 5'GGGTAACGCC and the microsatellite primer (GTG)5 yielded
      reproducible amplification patterns of sufficient clarity and variability to
      distinguish individual strains from the wild. UPGMA analysis tended to group the
      strains according to climatic and geographic origin. A comparative study of Ty1
      sequence having multiple chromosomal location was also done. Each wild S.
      paradoxus isolate shows a unique hybridization pattern allowing discrimination to
      the strain level.

PMID- 10879983
TI  - Molecular evidence for genus level diversity of bacteria capable of catalyzing
      anaerobic ammonium oxidation.
AB  - Recently, a bacterium capable to oxidize ammonium anaerobically at a high rate
      was identified as novel member of the Planctomycetales (Strous, M., Fuersi, J.
      A., Kramer, E. H. M., Logemann, S., Muyzer, G., van de Pas-Schoonen, K. T., Webb,
      R. I., Kufnen, J. G., and Jetten, M. S. M.: Nature 400, 446-449, 1999). Here we
      investigated the microbial community structure of a trickling filter biofilm with
      a high anaerobic ammonium oxidation activity. Fluorescence in situ hybridization
      (FISH) with a set of nine probes designed for specific identification of the
      recently described anaerobic ammonium oxidizer demonstrated that only one probe
      hybridized to bacteria within the biofilm. For phylogenetic characterization of
      putative biofilm anaerobic ammonium oxidizers a full-cycle 16S rDNA approach was
      performed by using a Planctomycetales-specific forward primer for PCR
      amplification. Of the twenty-five 16S rDNA fragments (1364 bp in length)
      amplified from the biofilm, nine were affiliated to the Planctomycetales.
      Comparative analysis showed that these sequences were more than 98.9% similar to
      each other but only distantly related to the previously recognized anaerobic
      ammonium oxidizer (below 91% similarity) and all other organisms represented in
      public 16S rRNA databases (similarities of below 79%). The retrieved sequences
      and the previously recognized anaerobic ammonium oxidizer represent two well
      separated groups of a deep-branching lineage within the Planctomycetales.
      Quantitative FISH analysis with a newly designed specific probe showed that the
      novel bacterium, provisionally classified as "Candidatus Kuenenia
      stuttgartiensis" constituted the dominant fraction of the biofilm bacteria. In
      situ probing revealed that ammonia-oxidizing bacteria of the beta-subclass of
      Proteobacteria were also present, albeit in significant smaller amounts, within
      the anoxic biofilm. Comparative sequence analysis of a stretch of the gene
      encoding ammonia-monooxygenase (amoA) demonstrated the occurrence of the DNA of
      at least three different populations of beta-subclass ammonia oxidizers within
      the biofilm.

PMID- 10879985
TI  - Riboprints as a tool for rapid preliminary identification of sphingomonads.
AB  - Fourtythree strains of the genus Sphingomonas and close relatives were subjected
      to riboprint analyses generated after digestion of genomic DNA with the
      restriction enzyme EcoRI and hybridization with E. coli rrnB operon. The majority
      of strains were characterized by a complex banding pattern in the riboprints.
      High degrees of similarities in the riboprints were only observed among strains
      of the same species such as S. yanoikuyae, S. aromaticivorans, S. subarctica and
      S. chlorophenolica. Strains of different species including close phylogenetic
      relatives such as S. asaccharolytica, S. mali and S. pruni were easily
      distinguished by the differences in the riboprints even after visual evaluation.
      Thus, our data demonstrate that riboprint analysis is useful for preliminary
      identification of new sphingomonad isolates at the species level.

PMID- 10879984
TI  - 16S rRNA-targeted oligonucleotide probes for the in situ detection of members of
      the phylum Cytophaga-Flavobacterium-Bacteroides.
AB  - Bacteria of the Cytophaga-Flavobacterium-Bacteroides phylum (CFB-phylum) are
      numerically important members of many microbial communities. A suite of five 16S
      rRNA-targeted oligonucleotide probes for members of this group is described which
      was designed to dominantly target bacteria of the CFB-phylum that are found in
      particular habitats. For this we initially performed a literature survey-for the
      sources and sites of isolation of hitherto described members of the CFB-phylum.
      Probe CFB286 is mostly complementary to the 16S rRNA of species originally
      isolated from freshwater habitats, however, detects some marine and soil isolates
      and is the only probe which includes some food isolates. Probe CFB563 detects
      marine as well as animal-associated isolates. Probe CFB719, which also detects
      some environmental isolates, and probe CFB972 are mostly targeting animal
      associated isolates. All probes are complementary to a variety of human
      associated species within the CFB-phylum which, in the data set investigated
      (October 1998), made up 46% of all 16S rRNA sequences from the CFB-phylum. We
      conclude that it is difficult to find habitat-specific probes for members of the
      CFB-phylum and that the design of probes for monophyletic groups should remain
      the standard approach. Applicability of the probes for fluorescence in situ
      hybridization and specificity for single cell detection were evaluated for the
      four mentioned probes whereas the fifth, probe CFB1082, which almost exclusively
      targets human-associated species, was not further characterized. The new probes
      are of limited determinative value and should be used together with the already
      established probes for the CFB-phylum. It is the hybridization pattern observed
      for a given cell or culture with the enlarged probe set that is suggestive for
      its affiliation with a defined group within the CFB-phylum.

PMID- 10879986
TI  - Nucleotide sequence of the 235 rRNA from Haloferax mediterranei and phylogenetic
      analysis of halophilic archaea based on LSU rRNA.
AB  - 23S rRNA gene from the halophilic archaeon Haloferax mediterranei (strain ATCC
      33500) was cloned and sequenced. Proceeding from the 2,912 nucleotides long
      sequence, the secondary structure of Haloferax genus large subunit rRNA was
      proposed. Haloferax mediterranei intergenic spacers 16S/23S and 23S/5S were also
      sequenced, and found to be 382 and 116 nucleotides long respectively. The 16S/23S
      spacer showed an Ala-tRNA intervening sequence, which is a common feature in
      Euryarchaeota. Sequence analysis of 23S rRNA and 16S rRNA was performed for the
      six organisms from the family Halobacteriaceae with both available gene
      sequences. Phylogenetic trees with completely different topology were obtained
      using both molecules.

PMID- 10879987
TI  - Amplified fragment length polymorphism (AFLP) analysis of Listeria monocytogenes.
AB  - AFLP analysis using four selective primers was performed on a set of 33 Listeria
      monocytogenes including strains from patients and foods implicated in outbreaks,
      human sporadic cases or foods. Strains were tested belonging to serovars 1/2a,
      1/2b, 1/2c, 3b, and 4b. Using one of the primers, the AFLP technique generated 20
      different sized DNA fragments. The 33 cultures segregated into 14 different
      patterns, each comprising 7-12 different fragments. Although the method was not
      sufficiently discriminatory for epidemiological typing, AFLP analysis reconfirmed
      the observation that L. monocytogenes comprises two major genetic groups: group 1
      includes strains of serovars 1/2a and 1/2c, while group 2 serovars 1/2b, 3b and
      4b.

PMID- 10879988
TI  - AFLP fingerprint analysis of Bradyrhizobium strains isolated from Faidherbia
      albida and Aeschynomene species.
AB  - The diversity of Bradyrhizobium isolates from Faidherbia albida and Aeschynomenee
      species was assessed using AFLP analysis, a high-resolution genomic
      fingerprinting technique. Reference strains from Bradyrhizobium japonicum,
      Bradyrhizobium elkanii and Bradyrhizobium liaoningense were included for
      comparison. At a similarity level of 50%, a total of 34 different groups were
      obtained by cluster analysis of the genomic fingerprints. Four of these clusters
      correspond to the three reference species, demonstrating the large diversity of
      the isolates studied. Comparison with other data demonstrates that AFLP has a
      higher resolution than restriction analysis of 16S rRNA genes, SDS-PAGE analysis
      of proteins and phenotypic analysis. Results of the latter two methods showed
      little correspondence with the genotypic data.

PMID- 10879989
TI  - Variation among strains of Xanthomonas campestris pv. vasculorum from Mauritius
      and other countries based on fatty acid analysis.
AB  - Fatty acid profiling was used to study variation amongst strains of Xanthomonas
      campestris pv. vasculorum (Xcv). They could be divided into five groups using
      cellular fatty acid profiles. Group A strains represent a new and little known
      taxon and all came from plants of broom bamboo (Thysanolaena maxima) from
      Mauritius. Group B strains included the Xcv pathotype reference strain and were
      from palms, broom bamboo and sugarcane from Mauritius, Reunion and Australia.
      Group C contained southern African and Malagasy strains from sugarcane and maize,
      together with X. campestris pv. holcicola strain. No Mascarene strains fell into
      this group. Group D strains isolated from sugarcane, maize and royal palm
      (Roystonea regia) were from Mauritius and Reunion, the earliest known strains
      coming from Reunion. These groups represented in the Mascarene Islands possibly
      belong to three different Xanthomonas species. A further Group E comprised one
      Xcv strain (NCPPB 182) from Puerto Rico, one X. vasicola pv. holcicola strain
      plus 6 other unclassified Xanthomonas strains causing red stripe disease symptoms
      in sugarcane. Three of these groups occur on Mauritius and two occur on Reunion.
      Group B strains originally caused serious problems in noble canes. As resistant
      interspecific hybrids were introduced, group D strains appeared in Mauritius
      possibly being introduced from Reunion but having similar host ranges within the
      Gramineae and Palmae. The findings that 3 of these groups (A, B, D) can cause
      gumming disease in a grass species (T. maxima) and that 2 of them (B, D) also
      cause gumming disease in sugar cane (Gramineae) and palms (Palmae) is unusual.

PMID- 10879990
TI  - Polyphasic identification of wild yeast strains isolated from Greek sourdoughs.
AB  - A total of forty-five wild yeast strains were isolated from five traditional
      Greek wheat sourdoughs. Strains were identified using the classical
      identification technique along with the sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of whole cell proteins (SDS-PAGE), Fourier transform-infrared
      spectroscopy (FT-IR) and the randomly amplified polymorphic DNA-polymerase chain
      reaction analysis (RAPD-PCR). The latter methods confirmed the classical
      identification. According to the results obtained, fourteen strains were
      identified as Saccharomyces cerevisiae strains, twenty-five as Pichia
      membranaefaciens strains and six as Yarrowia lipolytica.

PMID- 10879991
TI  - Lethal or life-threatening allergic reactions to food.
AB  - Fatal or life-threatening anaphylactic reactions to food occur in infants,
      children and adults. Atopic individuals with bronchial asthma and prior allergic
      reactions to the same food are at a particularly high risk, whereby even the mere
      inhalation of the allergenic food can be fatal. Not only peanuts, seafood and
      milk can induce severe, potentially lethal anaphylaxis, but indeed a wide
      spectrum of foods, according to the different patterns of food sensitivity in
      different countries. Foods with "hidden" allergens and meals at restaurants are
      particularly dangerous for patients with food allergies. Similarly, schools,
      public places and restaurants are the major places of risk. However, the main
      factor contributing to a fatal outcome is the fact that the victims did not carry
      their emergency kit with adrenaline (epinephrine) with them. In cases of death
      where food anaphylaxis is suspected, it is important for forensic reasons to
      preserve uneaten portions of the food in order to identify (hidden) allergens. It
      is also important to determine postmortem specific serum IgE, tryptase and
      histamine levels to document the anaphylaxis. There is a need to raise awareness
      of the diagnosis and treatment of anaphylaxis among doctors, those called upon to
      administer emergency medical care, and the public, and also to provide increased
      support for those with potentially fatal food allergies through the help of
      patients' organizations, and national and international medical societies. The
      food industry should ensure a policy of comprehensive labelling of ingredients so
      that even the smallest amount of potentially lethal foodstuffs can be clearly
      identified. Finally, the pharmaceutical industry should be persuaded to
      reintroduce an adrenaline inhaler onto the market.

PMID- 10879992
TI  - Further improvement of quality of life by cetirizine in perennial allergic
      rhinitis as a function of treatment duration.
AB  - The SF-36 Health Status Questionnaire is a generic quality of life questionnaire
      based on 36 questions selected to represent nine health concepts. Perennial
      allergic rhinitis is a disease which causes variable restrictions on the
      physical, psychological and social aspects of patients' lives. According to the
      SF-36 questionnaire assessment, quality of life is impaired in these patients.
      Cetirizine, a potent, reliable histamine H1-receptor antagonist, has already been
      found to induce significant improvement in the quality of life of patients with
      chronic rhinitis, as assessed by the same SF-36 questionnaire after 1 and 6 weeks
      of treatment. This paper further investigates the extent to which cetirizine
      continues to improve quality of life after a long-term treatment (6 weeks)
      compared to a shorter treatment (1 week). The analyses show that, despite the
      significant improvement found after 1 week of treatment with cetirizine compared
      to placebo, a further 5-week course of therapy not only maintains this
      improvement but continues to enhance quality of life significantly above and
      beyond this.

PMID- 10879994
TI  - Reproducibility and use of low-concentration skin prick test.
AB  - We aimed to evaluate the reproducibility of the skin prick test performed with
      serial 1:4 dilutions of commercial standardized extracts in comparison with serum
      specific IgE and the undiluted commercial extract. Twenty-four subjects
      sensitized to one (17 cases) or two (seven cases) inhalant allergens were
      selected and submitted to duplicate skin prick tests with concentrated commercial
      allergenic extracts or with serial 1:4 dilutions of the same extracts in two
      different examinations 7 days apart. Blood samples were obtained from 17 of the
      24 patients for specific IgE determination. No statistically significant within
      patient variations in the area of the wheal in skin prick tests done 1 week apart
      were found up to the eighth dilution (1:256) of the commercial allergen. On a
      patient-by-patient basis, only some dilutions showed a statistically significant
      correlation between allergen-specific IgE and the wheal area elicited by the same
      allergen, and a significant correlation was found between the wheal elicited by
      10 mg/ml histamine and both the concentrated and diluted allergens (up to the
      sixth dilution). In polysensitized patients, the allergen producing the largest
      wheal when used in concentrated form did not produce the same result when
      diluted. The skin prick test with low-potency allergens was reproducible in
      individual patients even after a 7-day interval up to a 1:256 dilution of the
      commercial extract, although there was no clear correlation with allergen
      specific IgE concentration. In polysensitized patients, the use of high-potency
      or low-potency allergens for skin prick tests can lead to different conclusions
      regarding the relative importance of each allergen.

PMID- 10879993
TI  - Importance of albumin in cross-reactivity among cat, dog and horse allergens.
AB  - Different allergenic proteins have been involved in cross-reactivity among
      animals. Albumins seem to be cross-sensitizing allergenic components. The aim of
      this study was to assess the importance of albumin as a cross-reactive allergen
      in patients sensitized to cat, dog and horse. One hundred and seventeen patients
      sensitized to cat were tested for IgE reactivity using skin prick tests and RAST
      assays with cat, dog and horse hair/dander extracts and their purified albumin
      extracts. RAST-inhibition studies were carried out to assess cross-reactivity
      among cat, dog and horse and among their purified albumins. It was found that 22%
      of patients exhibited specific IgE to cat albumin; 41% of patients sensitized to
      cat were also sensitized to dog and horse. Out of these patients, 21% had IgE to
      three albumins and 17% to two. Reciprocal inhibitions were observed among cat,
      dog and horse albumins and also among cat, dog and horse hair/dander extracts,
      using in the latter experiment sera from patients not sensitized to albumins. IgE
      binding to horse extract was inhibited 30% by its homologous albumin and IgE
      binding to cat and dog extracts in almost 15% by their respective albumins. It
      was concluded that albumins from these three animals share some epitopes that
      account for the cross-reactivity observed in around one-third of patients
      sensitized to cat, dog and horse. Nevertheless, more than 50% of specific IgE
      that cross-reacts among these three animals is directed to allergens other than
      albumin.

PMID- 10879995
TI  - Ganoderma lucidum: partial characterization of spore and whole body antigenic
      extracts.
AB  - This study focused on the characterization of antigenic/ allergenic profiles of
      Ganoderma lucidum spore and whole body preparations. Whole body G. lucidum
      contained higher protein to carbohydrate ratio whereas it was less than one for
      spore extract. Isoelectric focusing showed 12 and 11 bands in acidic pH range (pI
      3.5-6.5) for G. lucidum spore and whole body, respectively, while SDS-PAGE showed
      8 and 23 fractions, respectively, in molecular weight range of 12.8-75.0 kD. The
      prominent protein fractions of G. lucidum spores were 19.4, 22.8 and 23.8 kD,
      whereas for G. lucidum whole body, 13.2, 14.7, 18. 7, 21.5 and 23.5 constituted
      major fractions. Immunoblotting with 41 individual serum samples revealed 21.8,
      23.8, 19.4 and 20.0 kD to be major allergenic protein fractions of G. lucidum
      spores. The same using G. lucidum whole body and 26 individual serum samples
      identified several fractions of 17.0, 17.5, 18.5, 22.0, 23.8, 42.0, 44.0, 56.0
      and 69.0 kD as major allergens. The compiled data suggest that there are common
      as well as specific allergenic components in two G. lucidum extracts studied.

PMID- 10879996
TI  - Regulation of HLA-DR antigen in monocytes from colorectal cancer patients by in
      vitro treatment with human recombinant interferon-gamma.
AB  - During the immune response, a great number of cytokines that modulate the
      function of mononuclear phagocytes are produced. Since interferons are one of the
      most important cytokines, the aim of this study was to evaluate the expression of
      HLA-DR antigen after an 18-h culture with human recombinant interferon-gamma
      (hrIFN-gamma) on freshly isolated peripheral blood monocytes from 16 colorectal
      cancer patients and 16 healthy donors, using an indirect immunofluorescence
      method. The results obtained showed that there was a decreased percentage of HLA
      DR+ monocytes in the colorectal cancer patents (51 +/- 3%, p <0.01) compared with
      the healthy donors (77 +/- 2%). Treatment for 18 h with hrIFN-gamma increased the
      percentages of monocytes expressing HLA-DR: 71 +/- 3% for the cancer patients and
      84 +/- 2% for the healthy donors (p <0.01 and <0.001, respectively). Our results
      demonstrate that after in vitro treatment with hrIFN-gamma, functionally altered
      monocytes from colorectal cancer patients can reach major histocompatibility
      complex II antigen expression values similar to those of healthy donors, thus
      improving the host's cellular immune response against the tumor.

PMID- 10879997
TI  - Impact of Helicobacter pylori and Giardia lamblia infections on chronic
      urticaria.
AB  - The etiology of chronic urticaria is largely unknown. The role of Helicobacter
      pylori infection, which is the most important cause of gastritis and peptic
      ulcer, is not clear in the pathophysiology of chronic urticaria. In this study,
      we aimed to define the impact of H. pylori on chronic urticaria. Thirty-eight
      patients who had chronic urticaria of unknown origin and dyspepsia were included
      in the study. In all patients, standard laboratory tests for detection of
      urticaria etiology were performed. Mean urticaria symptom scores of patients were
      carried out. All patients underwent upper gastrointestinal endoscopy. The
      presence of H. pylori was investigated using urease testing and histopathology.
      Duodenal fluid aspirated during upper endoscopy was examined for the presence of
      Giardia lamblia. H. pylori infection was detected in 29 patients. After
      successful eradication of H. pylori infection, the mean symptom score of patients
      did not change significantly (2.6 +/- 0.6 vs., 2.4 +/- 0.8). Only one patient had
      a total disappearance of urticaria symptoms. Out of 38 patients, only one had G.
      lamblia infection. The results of our study suggest that there is no association
      between H. pylori infection and chronic urticaria.

PMID- 10879998
TI  - Tumor necrosis factor-alpha binding by peripheral blood lymphocytes and
      polymorphonuclear neutrophils in patients with multiple sclerosis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) in multiple sclerosis (MS) is responsible
      for peripheral blood leukocyte priming. The aim of this study was to evaluate
      fluorescein isothiocyanate (FITC)-labelled TNF binding ability by peripheral
      blood lymphocytes and polymorphonuclear neutrophils (PMNs) of MS patients,
      measured using flow cytometry (FACScan). Three groups of MS patients (total 34)
      were examined. Higher serum levels of TNF soluble receptors sp55 and sp75 were
      found in the MS patients during MS acute exacerbation (n = 10) and in chronic
      progressive forms (n = 11) as compared to MS remission (n = 13) and other
      neurological diseases (n = 14). Peripheral blood lymphocytes and PMNs of patients
      with acute exacerbation of MS bound TNF-FITC more effectively (p <0.01) as
      compared with the chronic progressive forms of MS, MS remission and other
      neurological diseases. The obtained results suggest a greater enhancement of TNF
      activity during MS acute exacerbation.

PMID- 10879999
TI  - A case of allergy to globe artichoke and other clinical cases of rare food
      allergy.
AB  - We describe herein four unusual clinical cases of rare allergy to foods in
      patients affected by allergic rhinitis and asthma. The patients were skin tested
      both with commercial food extracts and using prick-prick procedure with fresh
      foods. Total and specific IgE in serum were determined by REAST. Grapes, lupine
      seeds, black mulberry and artichoke resulted positive in the patients under
      study. This is the first time allergy to ingested artichoke has been described.

PMID- 10880000
TI  - Burning mouth syndrome due to cadmium in a denture wearer.
AB  - We report the case of a female denture wearer who was referred to our service due
      to burning of the lips and tongue but with no visible oral lesions. Her
      biochemical data, complete blood cell count, sedimentation rate, thyroid and sex
      hormones were normal. Tongue culture was negative. Patch tests, performed with a
      panel of 20 potential denture allergens, gave positive results (+++) only to a 2%
      petrolatum cadmium sulfate, which was present in the denture. Removal of the
      denture led to the clearing up of oral symptoms in 3 days. In light of these
      findings, carrying out patch tests with the allergens related to denture
      materials should be considered in these cases.

PMID- 10880001
TI  - Disseminated and recurrent sarcoid-like granulomatous panniculitis due to bovine
      collagen injection.
AB  - Three to five percent of patients treated with injectable collagen implants have
      adverse local reactions. Systemic signs or symptoms are infrequent. We describe
      the case of a 53-year-old woman who developed local and general complaints 2
      months after receiving two collagen injections in both nasolabial folds. She
      presented asthenia, malaise, polyarthralgia and inflammatory nodular panniculitis
      in the places of injection as well as on the forearms and lower extremities. Skin
      testing was compatible with hypersensitivity to collagen. This case raises the
      question as to whether the injection of animal-derived collagen induces
      manifestations similar to those observed in connective autoimmune diseases or
      human adjuvant disease.

PMID- 10880002
TI  - Divisive inhibition in recurrent networks.
AB  - Models of visual cortex suggest that response selectivity can arise from
      recurrent networks operating at high gain. However, such networks have a number
      of problematic features: (i) they operate perilously close to a point of
      instability, (ii) small changes in synaptic strength can dramatically modify the
      degree of amplification, and (iii) they respond slowly to rapidly changing
      stimuli. Divisive inhibition, acting through interneurons that are themselves
      divisively inhibited, can solve these problems without degrading the selectivity
      of a recurrent network.

PMID- 10880003
TI  - Scene dependence of the non-Gaussian scaling properties of natural images.
AB  - We report results on the scaling properties of changes in contrast of natural
      images in different visual environments. This study confirms the existence, in a
      vast class of images, of a multiplicative process relating the variations in
      contrast seen at two different scales, as was found in Turiel et al (Turiel A,
      Mato G, Parga N and Nadal J-P 1998 Self-Similarity Properties of Natural Images:
      Proc. NIPS'97 (Cambridge, MA: MIT Press), Turiel A, Mato G, Parga N and Nadal J-P
      1998 Phys. Rev. Lett. 80 1098-101). But it also shows that the scaling exponents
      are not universal: even if most images follow the same type of statistics, they
      do it with different values of the distribution parameters. Motivated by these
      results, we also present the analysis of a generative model of images that
      reproduces those properties and that has the correct power spectrum. Possible
      implications for visual processing are also discussed.

PMID- 10880004
TI  - Analysis of the elastic net model applied to the formation of ocular dominance
      and orientation columns.
AB  - The development and structure of orientation (OR) and ocular dominance (OD) maps
      in the primary visual cortex of cats and monkeys can be modelled using the
      elastic net algorithm, which attempts to find an 'optimal' cortical
      representation of the input features. Here we analyse this behaviour in terms of
      parameters of the feature space. We derive expressions for the OR periodicity,
      and the first bifurcation point as a function of the annealing parameter using
      the methods of Durbin et al (Durbin R, Szeliski R and Yuille A 1989 Neural
      Computation 1 348-58). We also investigate the effect of the relative order of OR
      and OD development on overall map structure. This analysis suggests that
      developmental order can be predicted from the final OR and OD periodicities. In
      conjunction with experimentally measured values for these periodicities, the
      model predicts that (i) in normal macaques OD develops first, (ii) in normal cats
      OR develops first and (iii) in strabismic cats OD develops first.

PMID- 10880005
TI  - Family secrets: disclosure of HIV status among gay men with HIV/AIDS to the
      family of origin.
AB  - A mail survey obtained a sample of 117 gay men with HIV/AIDS to examine levels of
      disclosure of HIV status to the family of origin and the association between
      disclosure and levels of support and barriers to support from the family. Among
      men with HIV there was a significant difference in knowledge of HIV status
      between family members such that mothers and siblings were more likely to be
      knowledgeable than fathers. For the total sample disclosure of HIV status was
      associated with higher levels of support from all family members and with a lower
      level of barrier to support from mothers and fathers. Implications for practice
      are discussed.

PMID- 10880006
TI  - AIDS: the development of a gender appropriate research intervention.
AB  - This study is part of an AIDS research-service project, implemented by a faculty
      member and graduate students from the University of Maryland, School of Social
      Work. It focuses on the last of the completed studies between 1993 and 1998. To
      access women-centered health care services in Washington, D.C., a four member
      team engaged in a gender-specific research intervention. Nine women with AIDS
      were hand picked and interviewed. The research team wanted the women with
      HIV/AIDS to have a forum in which to tell their stories, in their own words
      regarding their medical and social service needs. Anecdotal accounts from the
      researchers' journals provide descriptions for findings. Qualitative evaluation
      theories guided the development of the interview questions. This study explores
      demographic factors, method of contraction, symptoms, initial reactions, support
      systems, level of satisfaction and frustration with services, physical health
      care needs, social service needs, including legal, housing, financial and mental
      health needs of women living with HIV/AIDS. The literature search reaffirmed the
      gender related disparities of services offered found by the team in the field.
      Recommendations for service providers are given.

PMID- 10880007
TI  - Standardizing social indicators to enhance medical case management.
AB  - With the advent of Medicaid Managed Care, health care professionals and
      administrators have sought ways to increase patient compliance and appropriate
      utilization of services under a capitated system. The major focus has been on
      medical managed care and utilization review to control cost. This paper focuses
      on the development and standardization of social indicators to identify the
      biopsychosocial problems that cause medical noncompliance and inappropriate
      utilization of medical services by the Medicaid patient. The development of what
      is called Life Indicators is discussed and serves as a basis for enhancing the
      medical case management model to control cost when providing services to patients
      with complex medical and social problems.

PMID- 10880008
TI  - The knowledge and use of alternative therapeutic techniques by social work
      practitioners: a descriptive study.
AB  - A survey of use of alternative therapeutic methods was distributed to 1,000
      clinical/direct service social work practitioners; a sample of 321 reported on
      their use of alternative techniques. Approximately three-quarters of the
      respondcnts used or referred mind-body techniques or community health
      alternatives. These two techniques accounted for about two-thirds of all
      alternative practices. Manual healing was used or referred by about one-third of
      all practitioners and professionalized alternative medicine was used by about
      30%. Other methods, including botanical, pharmacological, and biological
      alternatives, diet and nutrition, and parapsychology were each used by fewer than
      10% of the respondents. Social workers were most knowledgeable about mind-body
      techniques and community-based alternatives.

PMID- 10880009
TI  - The search for legitimacy and the "expertization" of the lay person: the case of
      chronic fatigue syndrome.
AB  - Some "diseases" appear to be recognized first by sufferers. At times these
      diseases may be disclaimed by medical doctors and elusive to scientific
      categorization and description. In these cases sufferers may organize themselves
      together in support groups and lobby for money to finance the discovery of
      diagnostic markers that would legitimate and medicalize the constellation of
      symptoms that they experience. Chronic fatigue syndrome is such a disease; and it
      is characterized by varied and changing symptomatology. Its diagnostic markers
      are in the process of being refined. Presently, its diagnosis primarily
      originates in reports of subjective experience of extreme fatigue. Often-times
      people diagnose themselves after attending a support group and find a doctor
      through a support group network who believes in the disease. Sometimes, people
      then return to their own family doctors with information and try to teach their
      doctors about what they believe to be the nature of their disease, its prognosis
      and treatment. Through such paths as described in the paper, patients become
      "experts": they may often know more about the illness than doctors and non
      suffering others. This paper moves beyond the experience of chronic illness to
      describe the processes through which people seek confirmation and legitimation
      for the way that they feel and in a sense become the "experts."

PMID- 10880010
TI  - She can have a seizure maybe; then we can watch: the portrayal of epilepsy in
      film.
AB  - The study explores the portrayal of epilepsy in 23 films identified as involving
      seizures. Findings indicate that seizures are used in film to drive the
      narrative, enhance major characterization, add to minor characters and create
      distraction from other action. Epilepsy is primarily portrayed as one dimension
      of unsympathetic, out-of-control, and feared characters. Generally, depictions
      are out-dated and unrelated to present day treatment of the illness or control of
      its symptoms. Social workers are asked to advocate for more accurate portrayals,
      and a list of professional and self-help groups who work in this way is provided.

PMID- 10880011
TI  - Adenovirus as a gene therapy vector for hematopoietic cells.
AB  - Adenovirus (Adv)-mediated gene transfer has recently gained new attention as a
      means to deliver genes for hematopoietic stem cell (HSC) or progenitor cell gene
      therapy. In the past, HSCs have been regarded as poor Adv targets, mainly because
      they lack the specific Adv receptors required for efficient and productive Adv
      infection. In addition, the nonintegrating nature of Adv has prevented its
      application to HSC and bone marrow transduction protocols where long-term
      expression is required. There is even controversy as to whether Adv can infect
      hematopoietic cells at all. In fact, the ability of Adv to infect epithelium
      based targets and its inability to effectively transfect HSCs have been used in
      the development of eradication schemes that use Adv to preferentially infect and
      "purge" tumor cell-contaminating HSC grafts. However, there are data supporting
      the existence of productive Adv infections into HSCs. Such protocols involve the
      application of cytokine mixtures, high multiplicities of infection, long
      incubation periods, and more recently, immunological and genetic modifications to
      Adv itself to enable it to efficiently transfer genes into HSCs. This is a
      rapidly growing field, both in terms of techniques and applications. This review
      examines the two sides of the Adv/CD34 controversy as well as the current
      developments in this field.

PMID- 10880012
TI  - Interleukin-12 gene therapy of a weakly immunogenic mouse mammary carcinoma
      results in reduction of spontaneous lung metastases via a T-cell-independent
      mechanism.
AB  - In our previous studies using gene gun-mediated delivery of interleukin 12 (IL
      12) cDNA in vivo, we observed T-cell-mediated regression of established murine
      tumors and demonstrated the induction of systemic immunity in test animals. In
      this study, we further characterized the antitumoral and anti-metastatic effect
      of this gene therapy approach by employing two murine metastatic mammary tumor
      models: the immunogenic TS/A adenocarcinoma and the weakly immunogenic 4T1
      adenocarcinoma. In the TS/A model, gene transfer into the skin overlying an
      established intradermal tumor with an IL-12 cDNA expression vector resulted in
      complete tumor regression in 50% of mice followed by the development of
      immunological memory. In contrast, the growth of the intradermal 4T1 tumors was
      not affected by the IL-12 gene therapy protocol. However, this treatment resulted
      in a substantial reduction of spontaneous metastases in the lungs of 4T1 tumor
      bearing mice and significantly prolonged their survival time. T cells were not
      required for this anti-metastatic effect, because it was also observed in nude
      mice and in mice depleted of CD4+ and CD8+ T cells. Tumor-draining lymph node
      cells obtained from 4T1 tumor-bearing mice treated with IL-12 cDNA exhibited
      increased natural killer (NK) activity and produced enhanced levels of interferon
      gamma (IFN-gamma) compared with similar mice treated with luciferase cDNA. In
      addition, in vivo depletion of NK cells or neutralization of IFN-gamma resulted
      in partial suppression of the anti-metastatic effect of IL-12 gene therapy,
      suggesting the involvement of both NK cells and IFN-gamma in this effect.

PMID- 10880013
TI  - Thymidine kinase gene therapy with concomitant topotecan chemotherapy for
      recurrent ovarian cancer.
AB  - INTRODUCTION: Patients with recurrent ovarian cancer were treated with a
      replication-deficient recombinant adenovirus containing the herpes simplex virus
      thymidine kinase gene administered intraperitoneally (i.p.) followed by
      administration of an anti-herpetic prodrug and topotecan. MATERIALS AND METHODS:
      A total of 10 patients with stage IIIc epithelial ovarian cancer underwent
      secondary debulking to < or =0.5 cm residual tumor. Patients with normal i.p.
      flow received i.p. delivery of adenovirus. Two patients each were treated on dose
      level 1 (2 x 10(10) vector particles (VP)), dose level 2 (2 x 10(11) VP), and
      dose level 3 (2 x 10(12) VP); four patients were treated on dose level 4 (2 x
      10(13) VP). Acyclovir and topotecan were started 24 hours after vector delivery.
      RESULTS: No patient treated at any dose level incurred unanticipated toxic
      effects, and all side effects resolved. The most common adverse event was
      myelosuppression: grade 3 or 4 thrombocytopenia with grade 2-4 anemia in three
      patients and grade 3 or 4 neutropenia in eight patients. Three patients developed
      thrombocytosis and three patients had a mild elevation of serum glutamic pyruvic
      transaminase/alanine aminotransferase. Temperature elevations that were not
      associated with detectable infection occurred in two patients. DISCUSSION: I.p.
      delivery of adenoviral vector with concomitant topotecan chemotherapy was well
      tolerated without significant lasting toxicities. Side effects were independent
      of the dose of adenoviral vector.

PMID- 10880014
TI  - Breast cancer-specific expression of the Candida albicans cytosine deaminase gene
      using a transcriptional targeting approach.
AB  - We constructed a series of adenoviral (Ad) vectors that express the Candida
      albicans cytosine deaminase (CD) suicide gene under the transcriptional control
      of either the human alpha-lactalbumin (ALA) or ovine beta-lactoglobulin (BLG)
      promoter (Ad.ALA.CD and Ad.BLG.CD, respectively). The Ad.ALA.CD and the Ad.BLG.CD
      vectors converted the prodrug 5-fluorocytosine (5-FC) to the toxic nucleotide
      analog 5-fluorouracil in a breast cancer cell-specific manner, with a conversion
      rate of 40% and 52% in T47D cells and 50% and 41% in MCF7 cells, respectively. No
      significant conversion (< or =3%) was observed in an immortalized nontumorigenic
      breast epithelial cell line (MCF10A) and a human osteosarcoma cell line (U2OS).
      Adenovirus vector-based prodrug conversion of the 5-FC in T47D and MCF7 in the
      presence of 1 mg/mL of 5-FC led to cytotoxicity that resulted in a nearly
      complete cell death (> or =90%) after 5 days, whereas MCF10A and U2OS cells
      remained resistant (< or =10%). Nude mice harboring T47D-derived breast tumors
      that were injected intratumorally (i.t.) with therapeutic adenovirus vectors at a
      dose of 2 x 10(8) plaque-forming units and treated systemically with 5-FC at a
      concentration of 500 mg/kg/day showed a marked reduction in tumor mass within 30
      days when compared with animals that received vector alone. Animal survival was
      significantly prolonged after 72 days in mice treated with therapeutic vectors in
      conjunction with prodrug when compared with control animals. These preclinical
      data are sufficiently promising to warrant further studies of this
      transcriptional targeting approach to breast cancer treatment.

PMID- 10880015
TI  - Studies of direct intratumoral gene transfer using cationic lipid-complexed
      plasmid DNA.
AB  - Cationic lipid-mediated gene transfer is a safe and effective means of delivering
      potent immunomodulatory cytokines directly into tumors. This approach avoids
      undesirable side effects, including systemic toxicities. To investigate key
      factors affecting intratumoral (i.t.) gene transfer, cationic lipid-DNA complexes
      were injected into subcutaneous human melanoma tumors in severe combined
      immunodeficient mice. Animals received i.t. injections of VR1103, a DNA plasmid
      encoding the gene for human interleukin-2 (IL-2), either alone or complexed with
      the cationic lipid N-(1-(2,3-dimyristyloxypropyl)-N,N-dimethyl-(2-hydroxyethyl)
      ammonium bromide/dioleoyl phosphatidylethanolamine (DMRIE/DOPE). Tumors were
      subcultured and supernatants were tested for IL-2 secretion by enzyme-linked
      immunosorbent assay. IL-2 secretion was consistently higher when lipid:DNA (L:D)
      complexes were formulated at high L:D ratios (wt/wt), and IL-2 transgene
      expression increased in a DNA dose-dependent manner. A comparison of naked
      plasmid and lipid-complexed DNA revealed that lipid complexes were more effective
      for i.t. gene transfer. Using an enhanced green fluorescent protein reporter
      plasmid and flow cytometry, i.t. transfection efficiency was 1.74% (+/- 1.08%).
      Tumor injection technique, including injection volume and location, had a limited
      impact on i.t. gene transfer. These results indicate that the formulation and
      dosage of cationic L:D complexes, but not injection technique, play a key role in
      determining the level of i.t. transgene expression.

PMID- 10880016
TI  - Genetically engineered fibroblasts with antigen-presenting capability: efficient
      induction of an antigen-specific cytotoxic T-lymphocyte response and protection
      against tumor development in vivo.
AB  - BLK mouse fibroblasts (H-2b) were genetically engineered to express costimulatory
      B7.1 and interleukin-2 (BLK/IL2/B7.1). The BLK/IL2/B7.1 cells were then pulsed
      with an ovalbumin (OVA) epitope as a model antigen (Ag) (BLK/IL2/B7.1/OVA), and
      tested for the induction of OVA-specific cytotoxic T lymphocytes (CTLs) in
      C57BL/6 mice (H-2b). The genetically engineered fibroblasts lacking one or two of
      three factors (interleukin-2, B7.1, and OVA) were constructed and used as
      controls. Immunization with the BLK/IL2/B7.1/OVA cells induced strong cytotoxic
      activities against OVA-expressing EL4 (EG7) tumor cells, but not against other H
      2b tumor cells, such as EL4, C1498 and B16F1 cells. The magnitude of the
      cytotoxic response in mice with the BLK/IL2/B7.1/OVA cells was significantly
      higher than the response in mice immunized with any other cell constructs. CD8+ T
      cells with OVA-specific cytotoxic activities were predominant in mice immunized
      with the BLK/IL2/B7.1/OVA cells. Furthermore, immunization with the
      BLK/IL2/B7.1/OVA cells significantly prolonged the survival of mice, compared
      with any other cell constructs, when the mice were challenged with EG7 tumor
      cells at 2 weeks postimmunization. Induction of antitumoral CTL immunity by the
      BLK/IL2/B7.1/OVA cells was independent of host Ag-presenting cells and of CD4+ T
      cell and natural killer 1.1+ cell help. These results suggest that fibroblasts
      can be genetically modified to efficient Ag-presenting cells for the induction of
      an Ag-specific CTL response.

PMID- 10880017
TI  - Interleukin-2 gene-modified allogeneic melanoma cell vaccines can induce cross
      protection against syngeneic tumors in mice.
AB  - Vaccination using well-characterized allogeneic tumor cell lines expressing
      standardized doses of immunostimulatory cytokines is an attractive alternative
      for autologous gene-transfected tumor cell vaccines. In the present study, we
      show that vaccination with irradiated allogeneic K1 735 (H-2k) or B16F10 (H-2b)
      melanoma cells induces a moderate degree of cross-protection against the M-3
      melanoma (H-2d) in DBA/2 mice. Cross-protection against the syngeneic tumor was
      markedly improved when the allogeneic vaccines were transfected with the
      interleukin-2 (IL-2) gene. The IL-2 gene-modified allogeneic vaccines were
      effective for prophylactic vaccination against subsequent tumor challenge and for
      therapeutic vaccination against pre-existing tumor deposits, with efficacies that
      were comparable with that of the IL-2 gene-modified syngeneic vaccines. Cross
      protection correlated with the cytotoxic activity of splenocytes against M-3
      targets. Allogeneic vaccination was not effective in another model, against the
      B16F10 melanoma in C57BL/6 mice, irrespective of genetic modification with the IL
      2 or granulocyte-macrophage colony-stimulating factor genes.

PMID- 10880018
TI  - Improved radiosensitization of rat glioma cells with adenovirus-expressed mutant
      herpes simplex virus-thymidine kinase in combination with acyclovir.
AB  - Adenovirus expressing herpes simplex virus-thymidine kinase (HSV-TK) sensitizes
      internal rat glioma cells to radiation in combination with acyclovir (ACV).
      However, relatively high concentrations of ACV (>10 microM) are required to
      obtain significant radiosensitization. Serum levels rarely reach more than the
      lower micromolar range, preventing the full use of this genetic approach to
      radiosensitize cells in vivo. To better use the lower concentrations of ACV
      available in sera, we constructed an adenovirus expressing a mutant HSV-TK (HSV
      TK(75)) isolated for its approximately 20 times greater sensitivity to ACV than
      wild-type (wt) HSV-TK. We demonstrate that rat RT2 glioma cells infected with
      adenovirus AdCMV-TK(75) and exposed to either ACV or ganciclovir become more
      sensitive to lower concentrations (1-3 microM) of the drugs compared with cells
      infected with AdCMV-TK(wt), which expresses wt HSV-TK. Most importantly, the RT2
      cells become more sensitive to low doses (2-4 Gy) of 60Co radiation than cells
      infected with an adenovirus expressing wt HSV-TK. This sensitization is
      accompanied by an increased rate of apoptosis. In summary, we show that infection
      of rat glioma cells with an adenovirus expressing a mutant HSV-TK sensitizes the
      cells to low doses of radiation after exposure to ACV at lower concentrations
      than those required for wt HSV-TK. This finding suggests that this mutant
      adenovirus may improve the in vivo efficacy of HSV-TK-based cancer gene therapy
      approaches.

PMID- 10880019
TI  - Cre-loxP-mediated bax gene activation reduces growth rate and increases
      sensitivity to chemotherapeutic agents in human gastric cancer cells.
AB  - Dysregulation of apoptosis may be closely related to the development of cancer
      and its chemoresistance. Overexpression of Bax, an inducer of apoptosis, has led
      to increased cell death in a variety of cancer cell lines. In this study, we
      investigated the effect of Bax overexpression in two gastric cancer cell lines,
      MKN-28 and MKN-45, using a Cre-loxP-mediated inducible expression system. After
      induction of bax, both cell lines showed decreased proliferation, partially due
      to increased cell death. Furthermore, Bax-expressing MKN-28 cells were more
      sensitive to cisplatin. These results indicate that up-regulation of the bax gene
      may provide a novel strategy for the treatment of gastric cancer.

PMID- 10880020
TI  - Mdr1 promoter-driven tumor necrosis factor-alpha expression for a chemotherapy
      controllable combined in vivo gene therapy and chemotherapy of tumors.
AB  - Cancer gene therapy approaches are often designed as single-agent treatments;
      however, greater therapeutic effect might be obtained if combined with an
      established conventional treatment regimen such as chemotherapy. In this context,
      conditional promoters are useful tools, because they may be induced by
      therapeutic modalities. The human multidrug resistance gene (mdr1) promoter is
      inducible by cytostatic drugs and can be employed for the chemotherapy-regulated
      expression of therapeutic genes. In this in vivo study, the human mdr1 promoter
      fragment (-207 to +158) was used for drug-inducible expression of human tumor
      necrosis factor-alpha (TNF-alpha) in the vector construct pM3mdr-p-hTNF. The
      single doxorubicin and vincristine treatment of nude mice xenografted with pM3mdr
      p-hTNF-transduced MCF-7 mammary tumors resulted in drug-induced and time
      dependent elevation of intratumoral TNF-alpha expression at the mRNA and protein
      level. The highest drug induction was achieved at 2 days after drug application,
      as reflected by a maximum 25-fold increase in TNF-alpha secretion in the tumor.
      This drug-induced TNF-alpha expression is more effective in inhibiting tumor
      growth compared with the growth of tumors transduced with constitutively TNF
      alpha-expressing vectors in combination with chemotherapy.

PMID- 10880021
TI  - Targeting of adenoviral vectors through a bispecific single-chain antibody.
AB  - Recombinant adenoviral vectors are attractive in the context of cancer gene
      therapy because they are capable of delivering genes to a wide variety of
      tissues. The utility of adenoviruses is limited by their lack of specificity and
      by the absence of the receptor(s) for these viruses on many tumor cells.
      Redirecting adenoviral vectors to tissue- or tumor-specific targets can be
      achieved by using bispecific conjugates produced by chemical linkage of an anti
      adenovirus antibody (Ab) and a ligand or Ab directed toward a specific target. To
      avoid the limitations of chemical conjugates, molecular conjugates of anti-fiber
      knob and ligand have been proposed. We present here a novel strategy that allows
      the production of recombinant bispecific single-chain Abs directed at cell
      surface molecules. A construct was made that encodes a neutralizing anti
      adenovirus fiber single-chain Fv (scFv) Ab (S11) fused to a scFv Ab (425)
      directed against the epidermal growth factor receptor. The fusion protein
      markedly enhanced the infection efficiency of adenoviral vectors in epidermal
      growth factor receptor-expressing cell lines. The bispecific scFv could be
      purified and concentrated after binding of its 6His tag to a nickel column
      without significant loss of activity. This approach should permit the production
      of high quantities of active bispecific scFv for in vivo use. The universal
      design of the construct allows rapid screening for relevant specific scFv
      directed at cell surface antigens that can be incorporated into adenoviral
      targeting strategies.

PMID- 10880022
TI  - Ribozyme and free alkylated base: a dual approach for sensitizing Mex+ cells to
      the alkylating antineoplastic drug.
AB  - N-alkyl-nitrosoureas and alkyl-triazenes are alkylating antineoplastic drugs, the
      efficacy of which is strongly affected by the level of expression of the DNA
      repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). In tumors, MGMT
      activity reduces the chemotherapeutic potential of alkylating drugs; therefore,
      efforts have been made to down-regulate the protein. A partial sensitization of
      Mex+ cells to alkylating drugs has been obtained using either free alkylated
      bases or oligonucleotides targeted against MGMT mRNA. In the present work, O6
      methylguanine and a chemically modified ribozyme, without a cationic liposome as
      a carrier, were coadministered to CHO47 cells, which express a high level of
      human MGMT protein. The reduction of MGMT mRNA and protein enhanced the
      genotoxicity of the alkylating drug mitozolomide. Furthermore, the sensitivity of
      CHO47 cells is the same as that of CHO5 cells, which lack MGMT protein. These
      data indicate that a strategy in which both mRNA and protein are degradation
      targets can be successfully applied to down-regulate the MGMT gene.

PMID- 10880023
TI  - Comparison of methotrexate resistance conferred by a mutated dihydrofolate
      reductase (DHFR) cDNA in two different retroviral vectors.
AB  - We previously reported the protection of hematopoietic cells from methotrexate
      (MTX) toxicity using an N2-based double copy vector containing serine 31 (S31)
      mutated dihydrofolate reductase (DHFR) (DC/SV6S31). To examine whether the use of
      SFG-based dicistronic vectors will lead to improvement in gene transfer over the
      DC/SV6 vector, we compared the protection provided by MTX to NIH3T3 cells and
      hematopoietic progenitor cells infected with these retroviral constructs
      containing the S31 variant DHFR cDNA. In NIH3T3 cells, the 50% effective dose
      values of MTX conferred by the SFG vector were 8-fold higher than those obtained
      with the DC/SV6 vector. DHFR mRNA levels were 22-fold and 38-fold higher than
      that seen for the DC/SV6 vector according to Northern blot and real-time
      polymerase chain reaction analysis, respectively. However, DHFR protein
      expression and DHFR enzyme activity were only 1.5-fold and 2-fold higher in the
      SFG vector, respectively, indicating that the mRNA from the SFG vector is
      translated less efficiently than the mRNA generated from the DC/SV6 vector.
      Furthermore, the degree of MTX protection conferred by each vector in both mouse
      and human hematopoietic cells was the same. These results indicate that the in
      vitro transduction efficiency and transgene expression of human DHFR in
      hematopoietic progenitor cells is equally conferred by both vectors.

PMID- 10880024
TI  - T-lymphocyte function after retroviral-mediated thymidine kinase gene transfer
      and G418 selection.
AB  - Generation of an efficient graft-versus-leukemia (GVL) effect in patients with
      hematological malignancies who relapse after allogeneic bone marrow
      transplantation depends in part upon the number of infused T lymphocytes.
      Currently, a GVL reaction cannot be achieved without inducing concomitant graft
      versus-host disease (GVHD); thus, one strategy is to try to modulate this
      GVL/GVHD ratio. We engineered human T lymphocytes with herpes simplex virus
      thymidine kinase and neomycin resistance genes, with an LXSN-derived vector that
      confers a ganciclovir-specific sensitivity to the transduced T cells. We analyzed
      proliferation, interleukin-2 production, alloreactivity in a mixed lymphocyte
      culture, and clonogenicity during the different stages of retroviral infection
      and G418 selection. Our results confirm that a sufficient number of transduced T
      lymphocytes can be obtained after selection for clinical studies. Their
      proliferative activity, alloresponsiveness, and ability to produce and respond to
      interleukin-2 were retained. Compared with control populations, their
      clonogenicity, as assessed by limiting dilution assays, was reduced after
      retroviral infection and G418 selection by 1.6 and 2.9 logs, respectively, with
      both viral supernatant incubation and coculture procedures. This study shows that
      infection and selection with the thymidine kinase-neomycin resistance gene
      retroviral vector significantly reduces the number of functional T lymphocytes.
      This finding should be taken into account when establishing the dose of T
      lymphocytes necessary to trigger a modulated GVL/GVHD effect.

PMID- 10880025
TI  - Transduction of human pancreatic tumor cells with vesicular stomatitis virus G
      pseudotyped retroviral vectors containing a herpes simplex virus thymidine kinase
      mutant gene enhances bystander effects and sensitivity to ganciclovir.
AB  - We examined the suitability of Moloney murine leukemia virus (MLV) 4070A-, cat
      endogenous virus (CEV) RD114-, or vesicular stomatitis virus G (VSV-G)
      pseudotyped retroviruses containing the humanized enhanced green fluorescent
      protein (hEGFP) or one of two herpes simplex virus thymidine kinase (HSV-TK)
      genes to transduce and provide gene expression in human pancreatic tumor cells.
      Fluorescence-activated cell sorter analysis demonstrated that VSV-G-pseudotyped
      hEGFP vector infected a greater percentage of cells and generated more robust
      gene expression than MLV 4070A- or CEV RD114-pseudotyped vectors. Dot blot and
      Southern blot analysis of genomic DNA revealed up to 10-fold more gene copies in
      G418-selected VSV-G hEGFP vector-transduced cells compared with genomic DNA from
      cells transduced with MLV 4070A or CEV RD114 pseudotypes. Cells transduced with
      VSV-G pseudotypes of HSV-TK(WT) or the HSV-TK30 vectors were 5- to 10-fold more
      sensitive to ganciclovir (GCV) than other pseudotype-transduced cells. A 40- to
      61-fold difference in sensitivity to GCV was observed between cells transduced
      with VSV-G HSV-TK30 vector and cells transduced with MLV 4070A HSV-TK(WT) vector
      in vitro. A 13-fold reduction in tumor volume was observed in severe combined
      immunodeficient mice inoculated with PancTuITK30 cells compared with mice
      inoculated with PancTuITK(WT) cells during GCV treatment. We conclude that the
      choice of glycoprotein envelope and the potency of a particular suicide gene were
      therapeutically additive and increased the number of HSV-TK-positive cells and
      sensitivity toward GCV in human pancreatic tumors cells for prodrug gene therapy.

PMID- 10880026
TI  - Evaluation of ganciclovir-mediated enhancement of the antitumoral effect in
      oncolytic, multimutated herpes simplex virus type 1 (G207) therapy of brain
      tumors.
AB  - G207 is a multimutated, conditionally replicating herpes simplex virus type 1
      (HSV-1) that retains an intact viral thymidine kinase (HSV-tk) gene. The virus
      exhibits oncolytic activity in various tumors and is being evaluated in patients
      with recurrent malignant glioma. In view of the potential for ganciclovir (GCV)
      to either enhance or inhibit the antitumoral activity of HSV-tk-retaining HSV-1
      vectors, we evaluated the effect of GCV administration on the antitumoral
      activity of G207. In culture, addition of GCV either had no effect or inhibited
      the cytocidal action of G207 at replication-permissive temperatures, while it
      significantly increased the cell killing in three of the four cell lines studied
      when virus replication was inhibited at nonpermissive temperatures. Using a G207
      permissive immunocompetent mouse tumor model, subcutaneous N18 neuroblastoma in
      syngeneic A/J mice, we found that GCV treatment did not affect G207-mediated
      tumor growth inhibition at a variety of viral doses (10(5), 10(7), and 10(7) x 2
      plaque-forming units). In A/J mice harboring intracerebral N18 tumors, GCV
      administration had no significant effect on the prolongation of survival by G207
      inoculation. These findings suggest that GCV administration may not be beneficial
      to the efficacy of G207 tumor therapy under conditions that favor active viral
      replication, because the potential HSV-tk/GCV-mediated enhancement of G207
      oncolytic activity may be balanced out by the inhibitory action of GCV on viral
      replication.

PMID- 10880027
TI  - Treatment of rat experimental brain tumors by herpes simplex virus thymidine
      kinase gene-transduced allogeneic tumor cells and ganciclovir.
AB  - Transfer of the herpes simplex virus thymidine kinase (HSVtk) gene, followed by
      administration of ganciclovir (GCV), generates the "bystander effect," in which
      HSVtk-negative wild-type cells are killed by GCV, as are HSVtk-expressing cells.
      Our previous study demonstrated that intracranial 9L gliomas could be efficiently
      treated due to this bystander effect by injecting the 9L glioma cells transduced
      with the HSVtk gene in the vicinity of the preimplanted wild-type 9L glioma and
      then administering GCV. For a possible clinical application of the bystander
      effect-mediated cell killing, we tested HSVtkgene-transduced allogeneic C6 glioma
      cells (C6tk) instead of syngeneic 9L glioma cells transduced with the HSVtk gene.
      Fisher rats were implanted intracranially with wild-type 9L glioma cells,
      subsequently injected with C6tk cells at the same brain coordinate, and
      thereafter treated with GCV or saline. When the rats were treated with GCV, a
      significant retardation of tumor growth was observed by serial magnetic resonance
      imaging, although this growth retardation was less prominent than that observed
      with 9L glioma cells transduced with the HSVtk gene; consequently, survival was
      prolonged (P < .01). Tumors that received C6tk cells contained almost no HSVtk
      positive cells after treatment with GCV. Rejection of allogeneic tumor cells,
      although possibly incomplete in the brain, can also contribute to the safety of
      this therapeutic strategy.

PMID- 10880028
TI  - Absence of in vitro or in vivo bystander effects in a thymidine kinase-transduced
      murine T lymphoma.
AB  - Among the goals of an optimal gene transfer system are a predictably high
      efficiency of transfer and the ability to confer stable gene expression. An
      additional benefit of strategies designed to target tumor or effector cells could
      be the induction of a bystander effect. Although tumor killing by the bystander
      effect in vivo has been obtained in several types of malignant tumors, it has not
      been reported for T lymphomas. The goals of this work were to determine the
      stability of the expression of the herpes simplex virus type-1 thymidine kinase
      and the low-affinity receptor for nerve growth factor truncated of its
      intracellular domain (deltaLNGFR) genes inserted in a murine T lymphoma; in
      addition, we sought to determine whether a bystander effect (direct or indirect)
      was present after treatment of the transduced tumor with ganciclovir. This study
      demonstrates a high level of stable expression of both genes in the T lymphoma in
      vitro and in vivo. However, we could not detect direct or indirect bystander
      effects in vivo mediated by the herpes simplex virus thymidine kinase/ganciclovir
      system in this tumor of lymphocyte origin. This is the first report to
      investigate bystander effects in vivo on a T-cell lineage tumor; in addition,
      this report has implications for the therapeutic transfer of non-transformed,
      antigen-specific T cells in vivo.

PMID- 10880029
TI  - Inhibition of human hematopoietic tumor formation by targeting a repressor Myb
      KRAB to DNA.
AB  - In many hematopoietic malignancies, c-Myb, a nuclear transcription factor of
      hematopoietic cells, is an activated oncogene. To achieve a specific inhibition
      of hematopoietic tumor growth, an inducible fusion protein consisting of the Myb
      DNA binding domain (DBD) and the active repressor domain KRAB, the Kruppel
      associated box of the developmental zinc-finger protein KOX-1, was generated. The
      MybDBD-KRAB fusion protein is a potent repressor of Myb-induced gene expression
      from Myb-responsive reporter genes containing several Myb binding sites. MybDBD
      KRAB expressed in the human hematopoietic promyelocytic cell line HL60
      significantly reduces cell proliferation by inducing apoptosis. Expression of
      MybDBD-KRAB in subcutaneously injected HL60 cells leads to inhibition of tumor
      formation in nude mice. The MybDBD-KRAB effect is specific to cell lines
      expressing c-Myb. It is conceivable to fuse the KRAB domain to other DBDs of
      oncogenic transcription factors and target them to their respective DNA response
      elements to selectively drive tumor cells into apoptosis.

PMID- 10880030
TI  - Harvard report on cancer prevention volume 4: Harvard Cancer Risk Index. Risk
      Index Working Group, Harvard Center for Cancer Prevention.
AB  - OBJECTIVE: Prediction of cancer risk is a minor component of current health risk
      appraisals. Perception of individual cancer risk is poor. A Cancer Risk Index was
      developed to predict individual cancer risk for cancers accounting for 80% of the
      cancer burden in the United States. METHODS: We used group consensus among
      researchers at the Harvard Medical School and Harvard School of Public Health to
      identify risk factors as definite, probable and possible causes of cancer. Risk
      points were allocated according to the strength of the causal association and
      summed. Population average risk of cancer and cumulative 10-year risk was
      obtained from SEER data. Individual ranking relative to the population average
      was determined. The risk index was evaluated for validity using colon cancer
      incidence in prospective cohort data. RESULTS: The Harvard Cancer Risk Index
      provides a broad classification of cancer risk. Validation against cohort data
      shows good agreement for colon cancer. CONCLUSION: The Harvard Cancer Risk Index
      offers a simple estimation of personal risk of cancer. It may help inform users
      of the major risk factors for cancer and identify changes in lifestyle that will
      reduce their risk. It offers the potential for tailored health-promotion
      messages.

PMID- 10880031
TI  - Changing patterns of tonsillar squamous cell carcinoma in the United States.
AB  - OBJECTIVE: Tonsillar squamous cell carcinoma (SCC) may differ etiologically from
      other oral cancers. The aim of this study was to provide a detailed description
      of the incidence patterns of tonsillar SCC in the United States. METHODS:
      Population-based incidence data from the Connecticut Tumor Registry (period 1945
      1994) and from the SEER program (period 1973-1995) were used to calculate age
      standardized (US 1970) and age-specific incidence rates and confidence intervals
      (CIs). Linear regression was used to evaluate trends. RESULTS: The incidence of
      tonsillar SCC increased fourfold among white women in Connecticut during 1945
      1994 but remained rather constant in white men. During 1973-1995, incidence rates
      per million person-years were considerably higher in blacks (31.6; 95% CI: 29.0
      34.4 in men, and 9.6; 95% CI: 8.3-10.9 in women) than whites (14.8; 95% CI: 14.3
      15.3 in men, and 6.1; 95% CI: 5.8-6.4 in women). Men, but not women, who were
      younger than 60 years experienced significant annual increases in tonsillar SCC
      incidence during 1973-1995 (2.7% in blacks and 1.9% in whites). No similar
      increases occurred for oral SCC at non-tonsillar sites. CONCLUSION: Incidence
      rates of tonsillar SCC vary considerably by sex, race and time in a way that
      cannot be explained by changes in tonsillectomy practices alone. Changes in
      environmental risk factors, including changes in smoking patterns and an increase
      in oral human papillomavirus infections, may have contributed.

PMID- 10880032
TI  - Patterns of inpatient surgeries for the top four cancers in the United States,
      National Hospital Discharge Survey, 1988-95.
AB  - BACKGROUND: At a time when the population is aging and medical practices are
      rapidly changing, ongoing surveillance of surgical treatments for cancer is
      valuable for health services planning. METHODS: We used data from the National
      Hospital Discharge Survey for patients with discharge diagnoses of lung,
      prostate, female breast, and colorectal cancer during 1988-95 to estimate
      population-based rates and numbers of inpatient surgical procedures. RESULTS: In
      1988-91, rates of lobectomy for lung cancer were significantly higher in males
      than females. By 1994-95, the male/female differences had largely disappeared due
      to increasing trends among females and decreasing trends among males. During 1988
      95, surgeries on the large intestine for colorectal cancer, including right
      hemicolectomy and sigmoidectomy, decreased significantly, as did abdominoperineal
      resections of the rectum. Anterior resections of the rectum increased
      significantly. Radical prostatectomies for prostate cancer increased from 34,000
      in 1988-89 to 104,000 in 1992-93 and then decreased to 87,000 in 1994-95; rates
      followed a similar pattern. Finally, the number and rates of inpatient
      mastectomies for female breast cancer decreased over the study period (from
      219,000 to 180,000 and from 78.8 to 61.5 per 100,000, respectively). CONCLUSION:
      These trends in inpatient surgeries for the major cancers in the US probably
      reflect changes in disease occurrence and modified treatment recommendations.

PMID- 10880033
TI  - A graded work site intervention program to improve sun protection and skin cancer
      awareness in outdoor workers in Israel.
AB  - OBJECTIVES: A graded worksite intervention program to improve sun protection and
      skin cancer awareness of outdoor workers was implemented and evaluated
      longitudinally over a period of 20 months. METHODS: Outdoor male workers (144/213
      recruits) from geographically separated units of the Israel National Water
      Company were allocated to complete (n = 37), partial (n = 72) or minimal (n = 35)
      intervention groups. Subsequent to the assignment and training of local safety
      officers, an educational and medical screening package was provided to the
      corresponding groups either once, or repeatedly a year later. Personal sun
      protective gear was provided upon repeated intervention. Outcome measures were
      evaluated through self-response questionnaires administered prior to the first
      intervention pulse, and 8 months after the first and second interventions.
      RESULTS: A 15-61% improvement in sun-protection habits was noted in the entire
      study population 8 months after initialization, compared to no sunscreen use, 20%
      sun-exposed skin area and highest mean occupational exposure dose of 1.68 MED/day
      at pre-test. An even greater use of sunscreen was evident 1 year later in the
      complete and partial intervention groups, + 80% and + 52%, respectively. The
      baseline rate of self-examination of the skin in the same two groups (49%)
      increased significantly at post-test (+ 71% and + 53%, respectively).
      CONCLUSIONS: This integrated intervention program led to significantly improved
      sun protection and skin cancer awareness. Repeated intervention combined with the
      supply of sun-protective gear contributed to an even greater impact.

PMID- 10880034
TI  - Breast cancer risk and lifetime leisure-time and occupational physical activity
      (Sweden).
AB  - OBJECTIVE: To clarify whether type and timing of physical activity affect
      postmenopausal breast cancer risk. METHODS: In a population-based case-control
      study within the Swedish female population 50-74 years of age, 3347 women with
      invasive, postmenopausal breast cancer (84% of all eligible) and 3455 controls
      (82% of all selected) reported on past leisure-time physical activity. Record
      linkage to decennial census data (1960-1990) provided estimates of their
      occupational physical activity. Odds ratios with 95% confidence intervals were
      estimated by multivariate logistic regression. RESULTS: After adjustment for
      potential confounders, women in sedentary occupations during their reproductive
      years (25-44 years of age) had a 50% higher risk for postmenopausal breast
      cancer, compared to those with the physically most demanding jobs. Only the most
      recent leisure-time physical activity was associated with a significant risk
      reduction. Women with the combination of sedentary jobs and lack of leisure-time
      exercise had a three-fold higher risk of breast cancer, compared to the
      physically most active both inside and outside the workplace. CONCLUSION: Effects
      of occupational and leisure-time physical activity on breast cancer risk appear
      to have different latency times, and/or to be effect-modified by age or
      reproductive status. Although chance might explain our findings, it is advisable
      to consider type and timing of physical activity in future studies.

PMID- 10880035
TI  - Weight change and risk of postmenopausal breast cancer (United States).
AB  - OBJECTIVE: Although many studies have shown that higher weight increases the risk
      of postmenopausal breast cancer, some aspects of this association are unclear. In
      order to examine the risk associated with different patterns of weight change, we
      analyzed data from a large case-control study of postmenopausal breast cancer.
      METHODS: Participants included women aged 50 79 years (n = 5031) who are newly
      diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and
      Wisconsin. Similarly-aged population controls (n = 5255) were selected at random
      from driver's license files and Medicare beneficiary lists. Height, weight, and
      information on other breast cancer risk factors were ascertained by structured
      telephone interviews from 1992 to 1995, and logistic regression was used to
      estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals
      (CI). RESULTS: Women in the top quintile groups for height at age 20, recent
      weight, and recent body mass index had significantly increased risks of breast
      cancer. Among women who reached their highest adult weight at younger ages (<45
      years), increasing weight loss since that age was associated with a reduced risk
      of postmenopausal breast cancer (OR 0.90, CI 0.84 0.98, per 5 kg). However,
      weight loss among women whose highest weight occurred after age 45 was not
      associated with risk (OR 1.00, CI 0.95 1.05, per 5 kg). Weight gain since the
      lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06
      1. 11). Temporary weight cycling (weight loss followed by weight gain) was not
      associated with increased risk. CONCLUSIONS: Weight gain clearly increased risk
      of postmenopausal breast cancer. These data lend further support to efforts aimed
      at helping women avoid weight gain as they age.

PMID- 10880036
TI  - Lack of communication about familial colorectal cancer risk associated with
      colorectal adenomas (United States).
AB  - BACKGROUND: Sufficient evidence has accumulated to suggest that the first-degree
      relatives of patients diagnosed with colorectal adenomas before the age of 60 are
      at increased risk of colorectal cancer. The principal objective of this study was
      to assess the extent to which channels of communication exist between physicians,
      patients and their at-risk first-degree relatives regarding both familial risk
      and screening recommendations. METHODS: A telephone survey was conducted among 79
      patients (age < or = 60 years) with newly diagnosed colorectal adenomas.
      Information regarding patient demographics, awareness of familial risk, physician
      recommendations, and extent of communication with family members about their risk
      status and need for screening was ascertained. RESULTS: Forty-four (56%) of the
      79 eligible subjects completed the survey. Only 18 (41%) responders were aware
      that their first-degree relatives were at increased risk of colorectal cancer,
      and the majority claimed to have gained their awareness through sources other
      than their physicians. Only five (28%) of the 18 knowledgeable patients notified
      their at-risk relatives of their status, and only two (11%) communicated the need
      for screening. CONCLUSIONS: This survey demonstrates poor communication about
      familial colorectal cancer risk associated with colorectal adenomas, and
      highlights the need for novel strategies to both promote awareness and facilitate
      screening of at-risk relatives.

PMID- 10880037
TI  - Parental smoking, CYP1A1 genetic polymorphisms and childhood leukemia (Quebec,
      Canada).
AB  - OBJECTIVE: To evaluate the effect of parental smoking on childhood acute
      lymphoblastic leukemia and to determine if it is modified by child genetic
      polymorphisms. METHODS: We carried out a case-control study in Quebec, Canada,
      including 491 incident cases aged 0-9 years and as many healthy controls matched
      on age and sex. Each parent was interviewed separately with respect to smoking
      habits during and after pregnancy. In addition, we carried out a case-only
      substudy with 158 cases classified according to presence or absence of the
      alleles *2A, *2B, and *4 in the CYP1A1 gene. RESULTS: There were small risk
      increases with maternal smoking during the later trimesters. Interaction odds
      ratios were increased (although often not significantly) for the CYP1A1*4 allele
      at high levels of maternal smoking in the last trimesters and at low level of
      paternal postnatal smoking, and decreased for the CYP1A1*2B allele. The latter
      appeared to confer a protective advantage at low levels for maternal prenatal
      smoking and at high levels for paternal postnatal smoking. CONCLUSIONS: Reported
      smoking habits showed no association with leukemia; risks for genetic
      polymorphisms lacked precision but indicated that the effect of parental smoking
      could be modified by variant alleles in the CYP1A1 gene.

PMID- 10880038
TI  - Colon cancer screening, lifestyle, and risk of colon cancer.
AB  - OBJECTIVES: Sigmoidoscopy screening and fecal occult blood (FOB) tests have been
      demonstrated as effective ways to reduce mortality from colorectal cancer.
      However, most studies of colorectal cancer screening and cancer mortality have
      not taken into consideration lifestyle factors that could account for the
      observed associations. The purpose of this study was to determine the association
      between screening and incidence of colon cancer, taking into consideration
      important lifestyle factors. METHODS: We estimated the association between
      screening and colon cancer after taking into consideration health and lifestyle
      factors using data obtained as part of population-based case-control study of
      incident colon cancers. RESULTS: Sigmoidoscopy screening, especially as part of a
      checkup, was protective against incident colon cancer in both men (OR 0.56, 95%
      CI 0.44-0.77) and women (OR 0.53, 95% CI 0.33-0.77) after adjusting for other
      risk factors for colon cancer. For men, associations were stronger for distal
      tumors (OR 0.48, 95% CI 0.31-0.71) than for proximal tumors (OR 0.67, 95% CI 0.45
      1.11). We did not observe significant associations between FOB test and colon
      cancer. Differences in characteristics between those who were screened and not
      screened were also observed. Men were more likely to report having a
      sigmoidoscopy as part of a checkup than were women, as were people with higher
      levels of education. People who reported having a sigmoidoscopy as part of a
      checkup also reported eating diets lower in fat and higher in fiber, folate, and
      vegetables. Men were more likely to report higher levels of physical activity,
      and women were more likely to report taking hormone replacement therapy (HRT) if
      they also reported a sigmoidoscopy. Both men and women who reported a
      sigmoidoscopy for screening purposes were more likely to have a family history of
      colorectal cancer. CONCLUSIONS: These data provide additional support for the
      benefits of having a screening sigmoidoscopy. The associations between screening
      sigmoidoscopy and colon cancer do not appear to be the result of lifestyle
      factors.

PMID- 10880039
TI  - The cancer-preventive potential of Panax ginseng: a review of human and
      experimental evidence.
AB  - OBJECTIVE: We have reviewed the potential cancer-preventive and other relevant
      properties of Panax ginseng C. A. Meyer, which has been traditionally used as a
      natural tonic in Oriental countries. DATA IDENTIFICATION AND STUDY SELECTION:
      Publications on Panax ginseng and its relation to cancer were obtained from the
      Medline database (1983-1998) and by checking reference lists to find earlier
      reports. The reports cover experimental models and human studies on cancer
      preventive activity, carcinogenicity and other beneficial or adverse effects. In
      addition, possible mechanisms of chemoprevention by ginseng were considered.
      RESULTS: Published results from a cohort and two case-control studies in Korea
      suggest that the intake of ginseng may reduce the risk of several types of
      cancer. When ginseng was tested in animal models, a reduction in cancer incidence
      and multiplicity at various sites was noted. Panax ginseng and its chemical
      constituents have been tested for their inhibiting effect on putative
      carcinogenesis mechanisms (e.g., cell proliferation and apoptosis,
      immunosurveillance, angiogenesis); in most experiments inhibitory effects were
      found. CONCLUSION: While Panax ginseng C. A. Meyer has shown cancer-preventive
      effects both in experimental models and in epidemiological studies, the evidence
      is currently not conclusive as to its cancer-preventive activity in humans. The
      available evidence warrants further research into the possible role of ginseng in
      the prevention of human cancer and carcinogenesis.

PMID- 10880040
TI  - Bidis--the latest trend in U.S. teen tobacco use.

PMID- 10880041
TI  - Keratinocyte stem cells: targets for cutaneous carcinogens.

PMID- 10880042
TI  - No eczema without keratinocyte death.

PMID- 10880043
TI  - HIV and HIV dementia.

PMID- 10880044
TI  - Neuroprotection mediated by changes in the endothelial actin cytoskeleton.
AB  - Cerebral blood flow is regulated by endothelium-derived nitric oxide (NO), and
      endothelial NO synthase-deficient (eNOS-deficient; eNOS(-/-)) mice develop larger
      cerebral infarctions following middle cerebral artery (MCA) occlusion. We report
      that disruption of Rho-mediated endothelial actin cytoskeleton leads to the
      upregulation of eNOS expression and reduces the severity of cerebral ischemia
      following MCA occlusion. Mice treated with the Rho inhibitor Clostridium
      botulinum C3 transferase (10 microgram/d) or the actin cytoskeleton disrupter
      cytochalasin D (1 mg/kg) showed a two- to fourfold increase in vascular eNOS
      expression and activity. This increase in eNOS expression was not due to
      increases in eNOS gene transcription, but to prolongation of eNOS mRNA half-life
      from 10 +/- 3 hours to 24 +/- 4 hours. Indeed, endothelial cells overexpressing a
      dominant-negative Rho mutant (N19RhoA) exhibited decreased actin stress fiber
      formation and increased eNOS expression. Inhibition of vascular Rho guanosine-5'
      triphosphate binding activity by the 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase inhibitor simvastatin increased cerebral blood flow to ischemic regions
      of the brain, and mice treated with simvastatin, C3 transferase, or cytochalasin
      D showed smaller cerebral infarctions following MCA occlusion. No neuroprotection
      was observed with these agents in eNOS(-/-) mice. These findings suggest that
      therapies which target the endothelial actin cytoskeleton may have beneficial
      effects in ischemic stroke.

PMID- 10880045
TI  - T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role
      in eczematous dermatitis.
AB  - Clinical and histologic similarities between various eczematous disorders point
      to a common efferent pathway. We demonstrate here that activated T cells
      infiltrating the skin in atopic dermatitis (AD) and allergic contact dermatitis
      (ACD) induce keratinocyte (KC) apoptosis. KCs normally express low levels of Fas
      receptor (FasR) that can be substantially enhanced by the presence of IFN-gamma.
      KCs are rendered susceptible to apoptosis by IFN-gamma when FasR numbers reach a
      threshold of approximately 40,000 per KC. Subsequently, KCs undergo apoptosis
      induced by anti-FasR mAb's, soluble Fas ligand, supernatants from activated T
      cells, or direct contact between T cells and KCs. Apoptotic KCs show typical DNA
      fragmentation and membrane phosphatidylserine expression. KC apoptosis was
      demonstrated in situ in lesional skin affected by AD, ACD, and patch tests. Using
      numerous cytokines and anti-cytokine neutralizing mAb's, we found no evidence
      that cytokines other than IFN-gamma participate in this process. In addition,
      apoptosis-inducing pathways other than FasR triggering were ruled out by blocking
      T cell-induced KC apoptosis by caspase inhibitors and soluble Fas-Fc protein.
      Responses of normal human skin and cultured skin equivalents to activated T cells
      demonstrated that KC apoptosis caused by skin-infiltrating T cells is a key event
      in the pathogenesis of eczematous dermatitis.

PMID- 10880046
TI  - Antiviral treatment normalizes neurophysiological but not movement abnormalities
      in simian immunodeficiency virus-infected monkeys.
AB  - Simian immunodeficiency virus (SIV) infection of rhesus monkeys provides an
      excellent model of the central nervous system (CNS) consequences of HIV
      infection. To discern the relationship between viral load and abnormalities
      induced in the CNS by the virus, we infected animals with SIV and later
      instituted antiviral treatment to lower peripheral viral load. Measurement of
      sensory-evoked potentials, assessing CNS neuronal circuitry, revealed delayed
      latencies after infection that could be reversed by lowering viral load.
      Cessation of treatment led to the reappearance of these abnormalities. In
      contrast, the decline in general motor activity induced by SIV infection was
      unaffected by antiviral treatment. An acute increase in the level of the
      chemokine monocyte chemoattractant protein-1 (MCP-1) was found in the
      cerebrospinal fluid (CSF) relative to plasma in the infected animals at the peak
      of acute viremia, likely contributing to an early influx of immune cells into the
      CNS. Examination of the brains of the infected animals after return of the
      electrophysiological abnormalities revealed diverse viral and inflammatory
      findings. Although some of the physiological abnormalities resulting from SIV
      infection can be at least temporarily reversed by lowering viral load, the viral
      host interactions initiated by infection may result in long-lasting changes in
      CNS-mediated functions.

PMID- 10880047
TI  - CD8(+) T-cell autoreactivity to an HLA-B27-restricted self-epitope correlates
      with ankylosing spondylitis.
AB  - HLA-B27 is highly associated with ankylosing spondylitis (AS), but the mechanism
      is unknown. Among the HLA-B27 alleles, B*2709, which differs by one amino acid
      from the susceptible B*2705, is not associated with the disease. Here, we analyze
      the reactivity, in patients with AS and in healthy controls carrying the B*2709
      or B*2705 alleles, to an EBV epitope derived from LMP2 (236-244) and to a
      sequence-related self-peptide from vasoactive intestinal peptide receptor 1
      (VIP1R 400-408). We found that both B*2705(+) and B*2709(+) subjects possess LMP2
      236-244-specific, HLA-B27-restricted T cells, whereas only the B*2705(+)
      individuals respond significantly to VIP1R 400-408. These results prompted us to
      compare, by IFN-gamma ELISPOT analysis, the T-cell response to VIP1R 400-408 in
      patients with AS versus B*2705 healthy controls. The data show that VIP1R 400-408
      specific reactivity is a major feature of the patients with AS. These findings
      show, for the first time to our knowledge, a widespread reactivity in patients
      with AS against a self-epitope that exhibits some features of a putative
      "arthritogenic" peptide.

PMID- 10880048
TI  - Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular
      enlargement and collagen accumulation after experimental myocardial infarction.
AB  - Matrix metalloproteinase-9 (MMP-9) is prominently overexpressed after myocardial
      infarction (MI). We tested the hypothesis that mice with targeted deletion of
      MMP9 have less left ventricular (LV) dilation after experimental MI than do
      sibling wild-type (WT) mice. Animals that survived ligation of the left coronary
      artery underwent echocardiographic studies after MI; all analyses were performed
      without knowledge of mouse genotype. By day 8, MMP9 knockout (KO) mice had
      significantly smaller increases in end-diastolic and end-systolic ventricular
      dimensions at both midpapillary and apical levels, compared with infarcted WT
      mice; these differences persisted at 15 days after MI. MMP-9 KO mice had less
      collagen accumulation in the infarcted area than did WT mice, and they showed
      enhanced expression of MMP-2, MMP-13, and TIMP-1 and a reduced number of
      macrophages. We conclude that targeted deletion of the MMP9 gene attenuates LV
      dilation after experimental MI in mice. The decrease in collagen accumulation and
      the enhanced expression of other MMPs suggest that MMP-9 plays a prominent role
      in extracellular matrix remodeling after MI.

PMID- 10880050
TI  - Thyroid hormone resistance and increased metabolic rate in the RXR-gamma
      deficient mouse.
AB  - Vitamin A and retinoids affect pituitary-thyroid function through suppression of
      serum thyroid-stimulating hormone (TSH) levels and TSH-beta subunit gene
      expression. We have previously shown that retinoid X receptor-selective (RXR
      selective) ligands can suppress serum TSH levels in vivo and TSH-beta promoter
      activity in vitro. The RXR-gamma isotype has limited tissue distribution that
      includes the thyrotrope cells of the anterior pituitary gland. In this study, we
      have performed a detailed analysis of the pituitary-thyroid function of mice
      lacking the gene for the RXR-gamma isotype. These mice had significantly higher
      serum T4 levels and TSH levels than did wild-type (WT) controls. Treatment of RXR
      gamma-deficient and WT mice with T3 suppressed serum TSH and T4 levels in both
      groups, but RXR-gamma-deficient mice were relatively resistant to exogenous T3.
      RXR-gamma-deficient mice had significantly higher metabolic rates than did WT
      controls, suggesting that these animals have a pattern of central resistance to
      thyroid hormone. RXR-gamma, which is also expressed in skeletal muscle and the
      hypothalamus, may have a direct effect on muscle metabolism, regulation of food
      intake, or thyrotropin-releasing hormone levels in the hypothalamus. In
      conclusion, the RXR-gamma isotype appears to contribute to the regulation of
      serum TSH and T4 levels and to affect peripheral metabolism through regulation of
      the hypothalamic-pituitary-thyroid axis or through direct effects on skeletal
      muscle.

PMID- 10880049
TI  - The role of CD154-CD40 versus CD28-B7 costimulatory pathways in regulating
      allogeneic Th1 and Th2 responses in vivo.
AB  - We used signal transducer and activator of transcription 4 (STAT4) and STAT6 gene
      knockout (-/-) mice as recipients of fully mismatched cardiac allografts to study
      the role of T-cell costimulatory pathways in regulating allogeneic T-helper 1
      (Th1) versus Th2 responses in vivo. STAT4(-/-) mice have impaired Th1 responses,
      whereas STAT6(-/-) mice do not generate normal Th2 responses. Cardiac allografts
      from C57BL/6 mice were transplanted into normal wild-type (WT), STAT4(-/-), and
      STAT6(-/-) BALB/c recipients. STAT4(-/-) and STAT6(-/-) mice rejected their
      grafts with the same tempo as untreated WT recipients. CD28-B7 blockade by a
      single injection of CTLA4Ig induced long-term engraftment and donor-specific
      tolerance in all three groups of recipients. CD154 blockade by a single injection
      of MR1 was effective in prolonging allograft survival and inducing tolerance in
      STAT4(-/-) mice but was only marginally effective in STAT6(-/-) recipients and WT
      controls. In addition, a similar protocol of MR1 was ineffective in prolonging
      graft survival in CD28(-/-) BALB/c recipients, suggesting that the lack of
      efficacy seen in WT and STAT6(-/-) mice is not due to the presence of a
      functional CD28-B7 pathway. Furthermore, there was a similar differential effect
      of CD28-B7 versus CD154-CD40 blockade in inhibiting immune responses in animals
      immunized with ovalbumin and complete Freund's adjuvant. These novel data
      indicate that Th1 and Th2 cells are differentially regulated by CD28-B7 versus
      CD154-CD40 costimulation pathways in vivo and may have potential implications for
      the development of therapeutic strategies such as T-cell costimulatory blockade
      in humans.

PMID- 10880051
TI  - Heat shock protein 70 prevents secretagogue-induced cell injury in the pancreas
      by preventing intracellular trypsinogen activation.
AB  - Rodents given a supramaximally stimulating dose of cholecystokinin or its
      analogue cerulein develop acute pancreatitis with acinar cell injury, pancreatic
      inflammation, and intrapancreatic digestive enzyme (i.e., trypsinogen)
      activation. Prior thermal stress is associated with heat shock protein 70 (HSP70)
      expression and protection against cerulein-induced pancreatitis. However, thermal
      stress can also induce expression of other HSPs. The current studies were
      performed using an in vitro system to determine whether HSP70 can actually
      mediate protection against pancreatitis and, if so, to define the mechanism
      underlying that protection. We show that in vitro exposure of freshly prepared
      rat pancreas fragments to a supramaximally stimulating dose of cerulein results
      in changes similar to those noted in cerulein-induced pancreatitis, i.e., intra
      acinar cell trypsinogen activation and acinar cell injury. Short-term culture of
      the fragments results in HSP70 expression and loss of the pancreatitis-like
      changes noted after addition of cerulein. The culture-induced enhanced HSP70
      expression can be prevented by addition of either the flavonoid antioxidant
      quercetin or an antisense oligonucleotide to HSP70. Under these latter
      conditions, addition of a supramaximally stimulating concentration of cerulein
      results in trypsinogen activation and acinar cell injury. These findings indicate
      that the protection against cerulein-induced pancreatitis that follows culture
      induced (and possibly thermal) stress is mediated by HSP70. They suggest that the
      HSP acts by preventing trypsinogen activation within acinar cells.

PMID- 10880052
TI  - CTLA4Ig inhibits T cell-dependent B-cell maturation in murine systemic lupus
      erythematosus.
AB  - Long-term administration of CTLA4Ig prevents the onset of disease in systemic
      lupus erythematosus-prone (SLE-prone) NZB/NZW F1 mice. To determine the mechanism
      of this effect, we engineered an adenovirus that expresses murine CTLA4Ig.
      Administration of a single high dose of this virus results in long-term
      expression of CTLA4Ig in the serum and absence of an immune response to the
      adenoviral vector. We administered Ad-CTLA4Ig to 19- to 22-week-old NZB/NZW F1
      mice and evaluated the effect on anti-DNA antibody-producing B cells. We show
      that CTLA4Ig has a beneficial effect on murine SLE for as long as it is present
      in the serum. This effect is associated with decreased expansion of both the IgM
      and IgG autoreactive B-cell population, inhibition of immunoglobulin class
      switching, decreased frequency and altered pattern of somatic mutation, and a
      marked decrease in the numbers of activated CD4-positive T cells. In contrast,
      intrinsic B-cell hyperreactivity and the survival of plasma cells in the bone
      marrow, both of which are less dependent on T-cell help, appear to be unaffected
      by CTLA4Ig. High-dose CTLA4Ig did not induce permanent tolerance in this
      autoimmune disease model. Furthermore, although the mice survived in a
      conventional housing facility, treatment with Ad-CTLA4Ig was immunosuppressive.

PMID- 10880053
TI  - Divergent functions of angiotensin II receptor isoforms in the brain.
AB  - The renin-angiotensin system (RAS) plays a critical role in cardiovascular and
      fluid homeostasis. The major biologically active peptide of the RAS is
      angiotensin II, which acts through G protein-coupled receptors of two
      pharmacological classes, AT(1) and AT(2). AT(1) receptors, expressed in brain and
      peripheral tissues, mediate most classically recognized actions of the RAS,
      including blood pressure homeostasis and regulation of drinking and water
      balance. In rodents, two highly homologous AT(1) receptor isoforms, termed AT(1A)
      and AT(1B) receptors, are expressed at different levels in major forebrain
      cardiovascular and fluid regulatory centers, with AT(1A) expression generally
      exceeding AT(1B) expression, but the relative contributions of these receptor
      subtypes to central angiotensin II responses are not known. We used gene
      targeting in combination with a unique system for maintaining catheters in the
      cerebral ventricles of conscious mice to test whether there are differential
      roles for AT(1A) and AT(1B) receptors in responses elicited by angiotensin II in
      the brain. Here we show that the blood pressure increase elicited by centrally
      administered angiotensin II can be selectively ascribed to the AT(1A) receptor.
      However, the drinking response requires the presence of AT(1B) receptors. To our
      knowledge, this is the first demonstration of a primary and nonredundant
      physiological function for AT(1B) receptors.

PMID- 10880054
TI  - Vasopressin-induced von Willebrand factor secretion from endothelial cells
      involves V2 receptors and cAMP.
AB  - Vasopressin and its analogue 1-deamino-8-D-arginine vasopressin (DDAVP) are known
      to raise plasma von Willebrand factor (vWF) levels. DDAVP is used as a hemostatic
      agent for the treatment of von Willebrand's disease. However, its cellular
      mechanisms of action have not been elucidated. DDAVP, a specific agonist for the
      vasopressin V2 receptor (V2R), exerts its antidiuretic effect via a rise in cAMP
      in kidney collecting ducts. We tested the hypothesis that DDAVP induces vWF
      secretion by binding to V2R and activating cAMP-mediated signaling in endothelial
      cells. vWF secretion from human umbilical vein endothelial cells (HUVECs) can be
      mediated by cAMP, but DDAVP is ineffective, presumably due to the absence of V2R.
      We report that DDAVP stimulates vWF secretion in a cAMP-dependent manner in
      HUVECs after transfection of the V2R. In addition, vasopressin and DDAVP induce
      vWF secretion in human lung microvascular endothelial cells (HMVEC-L). These
      cells (but not HUVECs) express endogenous V2R, as shown by RT-PCR. Vasopressin
      induced vWF secretion is mimicked by DDAVP and inhibited by the selective V2R
      antagonist SR121463B. It is mediated by cAMP, since it is inhibited by the
      protein kinase A inhibitor Rp-8CPT-cAMPS. These results indicate that vasopressin
      induces cAMP-mediated vWF secretion by a direct effect on endothelial cells. They
      also demonstrate functional expression of V2R in endothelial cells, and provide a
      cellular mechanism for the hemostatic effects of DDAVP.

PMID- 10880055
TI  - Potential mechanisms of human natural killer cell expansion in vivo during low
      dose IL-2 therapy.
AB  - The continuous, in vivo infusion of low-dose IL-2 selectively expands the
      absolute number of human natural killer (NK) cells after 4-6 weeks of therapy.
      The mechanism responsible for this expansion is unknown and was examined in this
      study. NK cells cultured at low concentrations of IL-2, comparable to those found
      during in vivo therapy, proliferate for 6 days and then exit the cell cycle.
      However, NK cells in vivo did not traverse the S/G(2)/M phase of the cell cycle
      during low-dose IL-2 therapy. Low concentrations of IL-2 delay programmed cell
      death of NK cells but have the same effect on resting T cells that do not expand
      in vivo. When CD34(+) bone marrow hematopoietic progenitor cells are cultured for
      21 days with low concentrations of IL-2, they differentiate into CD56(+)CD3(-) NK
      cells, not T cells. Thus, the selective expansion of human NK cells during
      continuous in vivo infusion of low-dose IL-2 likely results from enhanced NK-cell
      differentiation from bone marrow progenitors, combined with an IL-2-dependent
      delay in NK-cell death, rather than proliferation of mature NK cells in the
      periphery.

PMID- 10880056
TI  - Albuterol-induced downregulation of Gsalpha accounts for pulmonary beta(2)
      adrenoceptor desensitization in vivo.
AB  - The aim of the present study was to develop a chronic in vivo model of pulmonary
      beta(2)-adrenoceptor desensitization and to elucidate the nature and molecular
      basis of this state. Subcutaneous infusion of rats with albuterol for 7 days
      compromised the ability of albuterol, given acutely, to protect against
      acetylcholine-induced bronchoconstriction. The bronchoprotective effect of
      prostaglandin E(2), but not forskolin, was also impaired, indicating that the
      desensitization was heterologous and that the primary defect in signaling was
      upstream of adenylyl cyclase. beta(2)-Adrenoceptor density was reduced in lung
      membranes harvested from albuterol-treated animals, and this was associated with
      impaired albuterol-induced cyclic adenosine monophosphate (cAMP) accumulation and
      activation of cAMP-dependent protein kinase ex vivo. Gsalpha expression was
      reduced in the lung and tracheae of albuterol-treated rats, and cholera toxin
      induced cAMP accumulation was blunted. Chronic treatment of rats with albuterol
      also increased cAMP phosphodiesterase activity and G protein-coupled receptor
      kinase-2, but the extent to which these events contributed to beta(2)
      adrenoceptor desensitization was unclear given that forskolin was active in both
      groups of animals and that desensitization was heterologous. Collectively, these
      results indicate that albuterol effects heterologous desensitization of pulmonary
      Gs-coupled receptors in this model, with downregulation of Gsalpha representing a
      primary molecular etiology.

PMID- 10880057
TI  - Cloning of novel soluble gp130 and detection of its neutralizing autoantibodies
      in rheumatoid arthritis.
AB  - In an attempt to isolate disease-associated autoantigens in rheumatoid arthritis
      (RA), we cloned a new autoantigen named gp130-RAPS, which is a novel soluble form
      of the IL-6 signal-transducing molecule gp130. gp130-RAPS is a 50-kDa protein
      translated from alternatively spliced mRNA and has a truncated form of gp130 with
      a unique sequence, Asn-Ile-Ala-Ser-Phe (NIASF), in its COOH-terminus. We observed
      serum antibodies to this NIASF sequence frequently in patients with RA, but not
      in those with other systemic rheumatic diseases or in healthy subjects. In RA,
      detection of those antibodies was significantly associated with disease activity
      indices such as serum C-reactive protein (CRP) levels, erythrocyte sedimentation
      rate, blood platelet counts, and serum IL-6 concentration. In vitro experiments
      revealed that gp130-RAPS inhibited IL-6 activity, and this inhibition was
      neutralized by antibodies to the COOH-terminus of gp130-RAPS derived from
      patients with RA. Thus, autoantibody to gp130-RAPS may play an important role in
      the progression of RA by promoting IL-6 activity. Inspection of autoantibodies to
      gp130-RAPS may become a practical clinical test for RA. gp130-RAPS and its
      autoantibody provide a new clue to the complicated pathogenesis of RA.

PMID- 10880059
TI  - Factors that influence adolescent adaptation to sickle cell disease.
AB  - OBJECTIVE: To examine whether psychosocial factors play a more important role
      than biomedical risk factors in predicting adolescent adaptation to sickle cell
      disease (SCD); to determine whether psychosocial factors moderate the
      relationship between biomedical risk factors and adaptation. METHODS: Ninety
      African American adolescents from the multisite Cooperative Study of Sickle Cell
      Disease were recruited to complete a battery that included measures of
      psychosocial status and psychological adaptation. Data regarding their health
      status were collected from medical records. RESULTS: The findings revealed that
      intrapersonal (self-esteem, social assertiveness), stress-processing (use of
      social support), and social ecological factors (family relations) were
      significant predictors of adaptation; however, biomedical factors did not predict
      adaptation. There was no evidence that psychosocial factors moderated the
      relationship between biomedical risk factors and adaptation. CONCLUSIONS:
      Psychosocial factors proved to be better predictors of adaptation than biomedical
      risk factors. Additional research is needed to better understand the nature of
      the interrelationships among biomedical risk factors, psychosocial factors, and
      adaptation.

PMID- 10880060
TI  - Everyday pain responses in children with and without developmental delays.
AB  - OBJECTIVE: To examine whether children with developmental delays respond to
      painful events differently than nondelayed children. METHODS: Sixty families
      participated. Children between the ages of 2 and 6 years were observed at daycare
      centers while engaged in usual daily activities, such as free play. Spontaneous
      painful incidents and the child's responses were recorded using an observational
      measure (Dalhousie Everyday Pain Scale) designed to capture pain behavior.
      RESULTS: Children with developmental delays (n = 24) displayed a less intense
      distress response to an equivocal pain event than nondelayed children (n = 36).
      Children with developmental delays were more likely to display no reaction
      following a pain event, whereas children without delays cried more often.
      Further, children with developmental delays engaged in fewer help-seeking
      behaviors and were less likely to display a social response following a pain
      event than nondelayed children. CONCLUSIONS: Children with developmental delays
      appear to react in a different manner to pain events than nondelayed children do;
      we discuss a possible socio-communicative deficit.

PMID- 10880058
TI  - Human allograft acceptance is associated with immune regulation.
AB  - The ultimate goal of transplantation is drug-free allograft acceptance, which is
      rarely encountered in transplant recipients. Using a novel human-to-mouse "trans
      vivo" delayed-type hypersensitivity assay, we assessed donor-reactive cell
      mediated immune responses in kidney and liver transplant patients, four of whom
      discontinued all immunosuppression. One of these subjects (J.B.) rejected his
      graft after 7 years of stable function, while the others (D.S., R.D., M.L.)
      continue to have excellent graft function 5, 28, and 4 years after the cessation
      of immunosuppression. PBMCs from J.B. exhibited strong responses to both donor
      and recall antigens whereas PBMCs from patients D.S., R.D., and M.L. responded
      strongly to recall, but not donor, antigens. Furthermore, when donor and recall
      antigens were colocalized, the recall response in these three patients was
      inhibited. This donor antigen-linked nonresponsiveness was observed in four other
      patients who are still maintained on immunosuppression. The weakness of donor
      reactive DTH responses in these patients is due to donor alloantigen-triggered
      regulation that relies on either TGF-beta or IL-10. In D.S., regulation is
      triggered by a single donor HLA Class I antigen, either in membrane-bound or
      soluble form. This demonstrates that allograft acceptance in humans is associated
      with an immune regulation pattern, which may be useful in the diagnosis and/or
      monitoring of transplant patients for allograft acceptance.

PMID- 10880061
TI  - Declining immune function in children and adolescents with hemophilia and HIV
      infection: effects on neuropsychological performance. Hemophilia Growth and
      Development Study.
AB  - OBJECTIVE: To determine whether declines in immune functioning are associated
      with changes in neuropsychological performance in children and adolescents with
      hemophilia who are infected with the human immunodeficiency virus (HIV). METHODS:
      Participants were 333 males with hemophilia, ages 6-19 years at entry. A baseline
      and four annual neuropsychological evaluations were given. A longitudinal growth
      curves analysis of data was performed to detect changes associated with declining
      immune function. The cohort was stratified into four groups: (1) HIV- (n = 126);
      (2) HIV+, average of first two and last two CD4 counts > or = 200, (n = 106; High
      CD4 group); (3) HIV+, average first two counts > or = 200, average last two
      counts < 200 (n = 41; CD4 Drop group); and (4) HIV+, average first two and last
      two counts < 200 (n = 60; Low CD4 group). RESULTS: There were significant
      differences among the four groups over time in nonverbal intelligence,
      perceptual/performance skills, nonverbal memory, academic achievement, and
      language. The Low CD4 group consistently showed the greatest decrement in
      performance. On measures showing a practice effect for repeated measurements, the
      Low CD4 group participants' scores remained stable over time, suggesting opposing
      effects of practice and HIV-related declines. Lowered academic performance
      relative to IQ was found in all groups. CONCLUSIONS: Declines in
      neuropsychological functioning are directly related to declines in immune
      functioning in HIV+ children, adolescents, and young adults with hemophilia.
      Hemophilia itself may be a risk factor for academic underachievement.

PMID- 10880062
TI  - The Impact-on-Family Scale: a test of invariance across culture.
AB  - OBJECTIVE: To test the cultural invariance of the Impact-on-Family Scale in order
      to make cross-cultural comparisons. METHODS: The Italian version of the scale was
      administered to mothers of children with chronic illnesses. Factorial invariance
      was examined to investigate whether the four factors found with the original
      United States (U.S.) scale could be replicated. RESULTS: The results clearly
      demonstrate the replicability of the first three factors, Financial Burden,
      Familial/Social Impact, and Personal Strain. In addition, internal consistency
      and the homogeneity of the items of the corresponding scales are satisfactory.
      However, the fourth factor, Mastery, could not be replicated, and the reliability
      of the corresponding scale is poor. Italian mothers scored significantly lower on
      the Financial Burden and on the Familial/Social Impact dimension, compared to the
      American sample. CONCLUSIONS: Three of the four factors of the Impact-on-Family
      Scale are useful for cross-cultural comparisons between U.S. and Italian samples.

PMID- 10880063
TI  - Brief report: parents of children undergoing bone marrow transplantation:
      documenting stress and piloting a psychological intervention program.
AB  - OBJECTIVE: To document levels of stress in parents of children undergoing bone
      marrow transplantation (BMT) over the course of hospitalization and to pilot a
      psychological intervention program designed to teach parents techniques for
      managing stress associated with their child's illness and hospitalization.
      METHODS: Twenty-two mothers of children (ages 2-16) undergoing BMT were followed
      prospectively from preadmission to three weeks posttransplant. Eleven mothers,
      randomly assigned to participate in a pilot intervention program, were compared
      with 11 control mothers receiving standard care preparation of their child's BMT.
      RESULTS: Repeated measures ANOVAs detected significant changes in stress over
      time, with most stress reported preadmission. Mothers in the intervention
      condition reported using more stress management techniques than mothers in the
      standard care condition, though the majority of analyses revealed no significant
      differences in stress between groups. CONCLUSIONS: Increased levels of parenting
      distress may occur pretransplant, suggesting the need for additional
      psychological intervention at that time.

PMID- 10880064
TI  - Brief report: Adolescents' attitudes toward epilepsy: further validation of the
      Child Attitude Toward Illness Scale (CATIS).
AB  - OBJECTIVE: To examine adolescents' attitudes toward having epilepsy using the
      Child Attitude Toward Illness Scale (CATIS) and to provide further psychometric
      validation of the scale in this population. METHODS: Participants were 197
      adolescents aged 11 to 17 years who completed the CATIS at two points and two
      external validation scales. Test-retest and internal consistency reliability and
      construct validity were computed. Analysis of variance was used to examine
      differences in attitudes according to gender, age, and epilepsy severity.
      RESULTS: Girls, older adolescents, and those with more severe epilepsy had more
      negative attitudes toward having epilepsy than boys, younger adolescents, and
      those with moderate or mild epilepsy, respectively. Psychometric analyses yielded
      excellent internal consistency reliability and good test-retest reliability. The
      CATIS was moderately correlated with self-esteem and mastery, supporting its
      construct validity. CONCLUSIONS: The CATIS is a useful and psychometrically sound
      tool to assess adolescents' attitudes toward having chronic illness.

PMID- 10880065
TI  - Brief report: relationship between HIV infection and WPPSI-R performance in
      preschool-age children.
AB  - OBJECTIVE: To determine the neurodevelopmental effects of perinatally acquired
      HIV infection on children of preschool age. METHODS: Participants included 40
      children infected with HIV between the ages of three and five and an equal number
      of noninfected controls individually matched according to ethnicity, age, sex,
      and prenatal drug exposure. Participants were administered the Wechsler Preschool
      and Primary Scale of Intelligence-Revised (WPPSI-R), upon which an analysis of
      subtest distribution was conducted. RESULTS: Whereas both groups evidenced mean
      IQ and subtest scores significantly below published norms, an effect for HIV
      group status was not found when a factor combining Performance IQ (PIQ) and
      Verbal IQ (VIQ) was analyzed. However, the group infected with HIV scored
      significantly lower than controls on the Block Design subtest. CONCLUSIONS: Gross
      cognitive deficits are not evident among preschool children infected with HIV
      relative to matched controls. However, this study does provides some evidence for
      more focal deficits. Further investigation with older children should be
      conducted.

PMID- 10880066
TI  - Brief report: birth status, medical complications, and social environment:
      individual differences in development of preterm, very low birth weight infants.
AB  - OBJECTIVE: To assess whether medical complications mediate the relationship
      between birth status (i.e., birth weight and gestational age) and developmental
      outcome of preterm, very low birth weight (VLBW) infants, as well as the role of
      the early social environment (maternal distress and social support) in infant
      development. METHOD: Birth status and medical complication information was
      collected during the child's NICU stay. Maternal distress was assessed with the
      Beck Depression Inventory and the Parenting Stress Index at 4 months corrected
      infant age. Social support was measured with the Dunst Scales at 4 months
      corrected age. Child development measures were collected at 4 and 13 months
      corrected age (Bayley MDI and PDI), and at 36 months chronological age (PPVT-R
      and Achenbach CBCL). RESULTS: Medical complications mediated the birth status
      outcome relationship at 4 and 13 months, but not at 36 months. The 36-month
      outcomes were predicted by 4-month maternal distress and social support.
      CONCLUSIONS: Prematurity and VLBW are indirectly related to early developmental
      outcome through their association with medical complications. However, by 36
      months, developmental outcomes are more closely related to aspects of the early
      social environment than to early physiological factors.

PMID- 10880067
TI  - In memoriam: Logan Wright, Jr., PhD (1933-1999).

PMID- 10880069
TI  - Temperature-sensitive polymer-nanoshell composites for photothermally modulated
      drug delivery.
AB  - Composites of thermally sensitive hydrogels and optically active nanoparticles
      have been developed for the purpose of photothermally modulated drug delivery.
      Copolymers of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) exhibit a lower
      critical solution temperature (LCST) that is slightly above body temperature.
      When the temperature of the copolymer exceeds the LCST, the hydrogel collapses,
      causing a burst release of any soluble material held within the hydrogel matrix.
      Gold-gold sulfide nanoshells, a new class of nanoparticles designed to strongly
      absorb near-infrared light, have been incorporated into poly(NIPAAm-co-AAm)
      hydrogels for the purpose of initiating a temperature change with light; light at
      wavelengths between 800 and 1200 nm is transmitted through tissue with relatively
      little attenuation, absorbed by the nanoparticles, and converted to heat.
      Significantly enhanced drug release from composite hydrogels has been achieved in
      response to irradiation by light at 1064 nm. We have investigated the release of
      methylene blue and proteins of varying molecular weight. Additionally, the
      nanoshell-composite hydrogels can release multiple bursts of protein in response
      to repeated near-IR irradiation.

PMID- 10880070
TI  - Enhancement of fracture repair in rats with streptozotocin-induced diabetes by a
      single injection of biodegradable microcapsules containing a bone formation
      stimulant, TAK-778.
AB  - The feasibility of using microcapsules containing a bone formation stimulant,
      (2R,4S)-(-)-N-(4-diethoxyphosphorylmethylphenyl)-1,2,4, 5-tetrahydro-4-methyl-7,
      8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxamide (TAK-778) to enhance fracture
      repair was assessed in rats with streptozotocin-induced diabetes. The release
      profile of the microcapsules was designed to mimic a dosing regimen of multiple
      injections of TAK-778 solution. The solution was injected locally every third day
      from day 0 (the day of operation) to day 27 according to several dosing regimens,
      and fracture repair was assessed at day 28. The production of callus was most
      prominent when TAK-778 solution was injected so that 50-75% of the total dose (5
      mg TAK-778/site) was administered during the first half of the treatment period.
      Thus, injectable microcapsules of 30 micrometer in mean diameter were prepared in
      order to release TAK-778 over 4 weeks using a biodegradable polymer, poly(d,l
      lactic/glycolic) acid, with a copolymer ratio of 85:15 (mol/mol) and an average
      molecular weight of 14,000. A single local injection of the microcapsules
      markedly enhanced fracture repair, which resulted in recovery of destructive
      bending strength of the bone at day 28. Histologically, the injection of TAK-778
      microcapsules stimulated both fibrous and cartilaginous proliferation and
      periosteal ossification in the callus at day 7; bony bridge formation was
      observed at day 28. At day 56, the callus was remodeled and cortical bony union
      was evidenced in the microcapsule-treated fractures compared with the controls,
      which showed only fibrous union.

PMID- 10880071
TI  - Individual plasma proteins detected on rough biomaterials by phase imaging AFM.
AB  - In the past several years, atomic force microscopy (AFM) has provided topographic
      images of adsorbed plasma proteins in situ at unprecedented resolution. Imaging
      has been limited to adsorbed protein on relatively smooth model substrates such
      as mica, graphite, or self-assembled monolayers on which the small height of the
      protein can be observed from the background. The inherent roughness of
      biomaterial surfaces has prevented observation of adsorbed proteins in
      topographic images. We report imaging isolated fibrinogen molecules adsorbed on
      National Heart Lung and Blood Institute (NHLBI) reference materials
      polydimethylsiloxane and low-density polyethylene in situ using phase imaging
      AFM. Fibrinogen, a plasma protein important for blood coagulation and platelet
      aggregation, was adsorbed from dilute solution onto reference biomaterial
      surfaces at sub-monolayer coverage. Tapping mode AFM was used to image the
      samples. For polydimethylsiloxane, the lateral size of the surface features is
      much greater than the dimensions of proteins. This allowed adsorbed proteins to
      be observed in topographic images. The phase imaging signal of tapping mode AFM
      provides information on differences in material properties of the surface, and
      was used to distinguish individual protein molecules from the underlying polymer
      surface. On the low-density polyethylene surface, characteristic topographical
      features are of the same magnitude as the protein molecules, so that protein
      cannot be distinguished from the surface using topographic images. However, phase
      images were used to successfully locate and characterize the distribution of the
      protein. Phase imaging was not able to distinguish fibrinogen adsorbed onto
      expanded polytetrafluoroethylene. The utility and limitations of the phase
      imaging technique for characterizing protein adsorption to rough surfaces is
      discussed.

PMID- 10880072
TI  - Mechanical properties of a dental ceramic coated by RF magnetron sputtering.
AB  - Metal and ceramic thin film coatings were deposited onto a dental ceramic via
      radio frequency (RF) magnetron sputtering. The objectives of the study were to
      determine if a coherent interface could be produced between the coating and the
      substrate and if the coating significantly would improve the mechanical
      properties of the ceramic. Thin films of Au, Al, and AlN were deposited in this
      study. Mechanical testing results indicated that a significant improvement in
      flexural strength was observed with both Au and Al coatings while significant
      improvements in the flexural modulus were observed with all three materials. SEM
      analysis indicated that the interfaces were coherent and also suggested two
      mechanisms (crack bridging and crack blunting) that could be responsible for the
      enhanced mechanical properties.

PMID- 10880073
TI  - Poly(ethylenimine)-mediated transfection: a new paradigm for gene delivery.
AB  - Poly(ethylenimine) (PEI) is a synthetic polycation that has been used
      successfully for gene delivery both in vitro and in vivo due, in theory, to a
      form of protection that is afforded to the carried plasmids. In this study the
      stability of PEI/DNA complexes was demonstrated using deoxyribonuclease (DNase) 1
      and DNase 2, various levels of pH, and increasing exposure times. DNA that was
      complexed with PEI was not degraded when exposed to at least 25 Units of either
      enzyme for 24 h while uncomplexed forms of the same plasmid were digested when
      exposed to 0.010 Units of DNase 1 for 0.05 h or 0. 003 Units of DNase 2 for 1 h.
      For further comparison, the stability of complexes made with poly(L-lysine) (PLL)
      and DNA was examined and found to be lower than that of PEI/DNA complexes; PLL
      complexed DNA was digested on exposure to 1.25 Units of DNase 1 for 3 min. Cells
      were transfected with PEI/DNA complexes and, by using a pH indicator and optical
      recording techniques, it was found that the normal lysosomal pH value of 5.0 was
      not altered, bringing into question PEI's hypothesized lysosomal entry. Confocal
      microscopy showed that PEI/DNA complexes and lysosomes do not merge during
      transfection (although PLL/DNA complexes do). The lack of lysosomal involvement
      in PEI-mediated transfection is surprising because it goes against the
      conventional wisdom that has attempted to explain how PEI functions during
      transfection. PEI forms a stable complex with DNA, which moves from endocytosis
      to nuclear entry without significant cellular obstacles.

PMID- 10880074
TI  - Biorecognition of HPMA copolymer-lectin conjugates as an indicator of
      differentiation of cell-surface glycoproteins in development, maturation, and
      diseases of human and rodent gastrointestinal tissues.
AB  - Lectins are proteins that bind glycoproteins; binding patterns are altered with
      changes in glycoprotein expression accompanying maturation or disease. Binding of
      two lectins, wheat germ agglutinin (WGA) and peanut agglutinin (PNA), in human
      and rodent colon were previously examined. Normal tissue showed intense WGA
      binding; PNA binding was minimal. Diseased tissues showed increased PNA binding.
      We hypothesized that N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-lectin
      drug conjugates could deliver therapeutic agents to diseased tissues by targeting
      colonic glycoproteins. We examined biorecognition of free and HPMA copolymer
      conjugated WGA and PNA and anti-Thomsen-Friedenreich (TF) antigen antibody
      binding in normal neonatal, adult, and diseased rodent tissues, human specimens
      of inflammation, and Barrett's esophagus. Neonatal WGA binding was comparable to
      the adult, with additional luminal columnar cell binding. PNA binding was more
      prevalent; luminal columnar cell binding existed during the first 2.5 weeks of
      life. WGA binding was strong in both normal and diseased adult tissues; a slight
      decrease was noted in disease. PNA binding was minimal in normal tissues;
      increases were seen in disease. Anti-TF antigen antibody studies showed that PNA
      did not bind to the antigen. The results suggest that HPMA copolymer-lectin-drug
      conjugates may provide site-specific treatment of conditions such as colitis and
      Barrett's esophagus.

PMID- 10880075
TI  - Polyethylene glycol-coated biocompatible surfaces.
AB  - Surfaces covered with polyethylene glycol (PEG; HO-(CH(2)-CH(2)-O)(n)-H) have
      been shown to be biocompatible because PEG's properties yield nonimmunogenicity,
      nonantigenicity, and protein rejection. To produce a biocompatible surface
      coating, we have developed a method for grafting PEG onto activated silica films.
      We first deposited an amorphous silica film by plasma-enhanced chemical vapor
      deposition from SiH(4) and O(2) gases, which provided the flexibility to coat
      diverse materials with different chemistries and shapes. The silica films were
      activated by exposure to water plasma, increasing the number of silanol groups
      (Si-OH) on their surface. The surface silanol groups were then chemically reacted
      with the hydroxyl end of PEG to form an ester bond, Si-O-C, and to cover the
      surface with PEG. The surface reactions were monitored using attenuated total
      reflection Fourier transform infrared spectroscopy. The vibrational absorption
      bands of the C-O and -CH(2) bonds increased with time and saturated, indicating
      that PEG was adsorbed to saturation coverage on the surface. Simultaneously, the
      Si-OH absorption band decreased, showing that the surface silanols reacted with
      PEG and were depleted. The PEG-covered surfaces were physically characterized by
      atomic force microscopy, Auger electron spectroscopy, ellipsometry, and contact
      angle measurements. These characterization techniques provided additional
      evidence for the existence of chemically bonded PEG on the surfaces. Efficacy of
      protein rejection on PEG-covered surfaces was studied through measurements of the
      fluorescence intensity of Texas red-labeled bovine serum albumin brought in
      contact with such surfaces in solution. Significantly less protein adsorption was
      observed on surfaces covered with PEG compared to uncovered surfaces.

PMID- 10880076
TI  - Surface and bulk modifications to photocrosslinked polyanhydrides to control
      degradation behavior.
AB  - A unique class of surface-eroding polyanhydrides was developed and explored for
      use in medical applications requiring high-strength biomaterials (e.g.,
      orthopedics). In particular, dimethacrylated anhydride monomers were synthesized
      that photopolymerize quickly to render densely crosslinked polymer networks that
      degrade from the surface only by hydrolysis of labile anhydride linkages.
      Previous research on these materials has shown that the rate of hydrolysis of the
      degradable linkages is dependent on the hydrophobicity of the network
      composition. This article demonstrates the versatility in controlling the
      degradation process and resulting cellular response in these materials through
      the incorporation of new chemistries and the formation of polymer-polymer
      composite structures. Specifically, the rate of mass loss was controlled by the
      addition of hydrophobic linear polymers [e.g., poly(methyl methacrylate)] or
      monovinyl monomers based on hydrophobic natural components (e.g., cholesterol,
      steric acid). In addition, a newly established photografting method was used to
      modify the network surface chemistry with cholesterol- and stearic acid-based
      polymer grafts to control the degradation front and cellular interactions at the
      polymer-tissue interface. Finally, a porogen leaching method was used to form
      porous polyanhydride constructs, which can be subsequently filled with
      osteoblasts photoencapsulated in a hydrogel, as potential synthetic allograft
      materials for tissue engineering bone.

PMID- 10880077
TI  - G-protein activity requirement for polymethylmethacrylate and titanium particle
      induced fibroblast interleukin-6 and monocyte chemoattractant protein-1 release
      in vitro.
AB  - Periprosthetic granulomatous membranes consisting of fibroblasts, macrophages,
      lymphocytes, foreign body giant cells, and abundant particulate debris occur at
      sites of implant loosening. Previous studies demonstrate that fibroblasts respond
      to particulate debris through the release of interleukin-6 (IL-6), prostaglandin
      E(2), and matrix metalloproteinases in vitro. C-C chemokines are observed in
      granulomatous tissue surrounding loosened prosthetic implants and are released by
      macrophages and fibroblasts in response to particle challenge in vitro. This
      study tested the hypothesis that G protein activity is required for fibroblast
      activation by titanium and polymethylmethacrylate (PMMA) particles, and that
      inhibition of G protein activity would alter IL-6 and and monocyte
      chemoattractant protein-1 (MCP-1) release from activated fibroblasts. The
      specific inhibitor of G protein activity, pertussis toxin, was added to the
      fibroblasts to examine the effects of G protein activity with respect to the
      production of IL-6 and MCP-1 by orthopedic biomaterial-challenged fibroblasts in
      vitro. Interleukin-1beta (IL-1beta), a proven activator of MCP-1 and interleukin
      6, was used as a positive control. Exposure of fibroblasts to titanium and
      polymethylmethacrylate (PMMA) particles resulted in a dose-dependent release of
      MCP-1 and IL-6. Challenge with PMMA particles at doses of 0.150%, 0.300%, and
      0.600% vol/vol increased the release of interleukin-6 by 7-, 19-, and 22-fold,
      respectively, compared to fibroblasts exposed to serum-free culture medium alone
      at 24 h. Challenge with PMMA particles at doses of 0.075%, 0.150%, 0.300%, and
      0.600% vol/vol increased the release of MCP-1-6 by 2.5-, 3.6-, 4. 3-, and 4.5
      fold, respectively, compared to fibroblasts exposed to serum-free culture medium
      alone. Challenge with titanium particles at concentrations of 0.075%, 0.150%,
      0.300%, and 0.600% vol/vol increased the release of interleukin-6 by 2.6-, 6.4-,
      9.6-, and 10. 0-fold, respectively, compared to fibroblasts exposed to serum-free
      culture medium alone at 24 h. Challenge with titanium particles at concentrations
      of 0.038%, 0.075%, 0.150%, 0.300%, and 0.600% vol/vol increased the release of
      MCP-1 by 2.9-, 3.1-, 5.8-, 5.4-, and 5. 8-fold, respectively, compared to
      fibroblasts exposed to serum-free culture medium alone. Pretreatment of
      fibroblasts with pertussis toxin inhibited the release of interleukin-6 and MCP-1
      from PMMA and titanium particle challenged fibroblasts in a dose-dependent
      manner. PMMA particle induced fibroblast IL-6 release was inhibited by 23.6% and
      35.3% with 20- and 200-ng/mL doses of pertussis toxin, respectively. Titanium
      particle induced fibroblast IL-6 release was inhibited by 48.2% and 56.3% with 20
      and 200-ng/mL doses of pertussis toxin, respectively. PMMA particle-induced
      fibroblast MCP-1 release was inhibited by 36.0%, 50.4%, and 60.1% with 2-, 20-
      and 200-ng/mL doses of pertussis toxin, respectively. Titanium particle-induced
      fibroblast MCP-1 release was inhibited by 15.5%, 53.2%, and 64.6% with 2-, 20-,
      and 200-ng/mL doses of pertussis toxin, respectively. This study suggests that
      fibroblasts localized in periprosthetic membranes are a source of macrophage
      chemoattractant factors and proinflammatory mediators that may influence
      granuloma formation and lead to periprosthetic bone resorption. Furthermore, this
      study shows that G proteins are involved in particle-induced fibroblast
      activation, as evidenced by decrease levels of particle induced IL-6 and MCP-1
      release following pertussis toxin treatment. (c) 2000 John Wiley & Sons, Inc.

PMID- 10880078
TI  - Resorbable calcium phosphate particles as a carrier material for bone marrow in
      an ovine segmental defect.
AB  - Resorbable calcium phosphate ceramics are only osteoconductive; therefore, their
      combination with osteogenic substances may lead to stimulation of bone healing.
      In the present study this combination, using autologous bone marrow, was
      investigated. In 31 sheep, a 3-cm tibial segmental defect was created and
      stabilized with an intramedullary nail. The animals were divided into four
      groups: empty defects (group 1, n = 7), and defects filled with 10-mL dense
      resorbable calcium phosphate particles (group 2, n = 8), with 10-mL particles
      soaked in bone marrow (group 3, n = 8), or with 10-mL autologous bone (group 4, n
      = 8). On evaluation after 12 weeks, significantly higher values were seen in
      group 3 than in group 2 for callus volume (p = .016), bone mineral density ratio
      (p = .03), bone mineral content ratio (p = .04), torsional strength (p = .005),
      and torsional stiffness (p = .01). For all end points, the outcome of group 3 was
      lower than that of group 4. In the histology, there was direct contact between
      newly formed bone and remnants of the particles. There were no signs of
      inflammatory reactions. Although a stimulatory effect of bone marrow was seen,
      the combination of resorbable calcium phosphate particles with bone marrow does
      not provide an alternative for autologous bone grafting.

PMID- 10880079
TI  - Engineering three-dimensional bone tissue in vitro using biodegradable scaffolds:
      investigating initial cell-seeding density and culture period.
AB  - New three-dimensional (3D) scaffolds for bone tissue engineering have been
      developed throughout which bone cells grow, differentiate, and produce
      mineralized matrix. In this study, the percentage of cells anchoring to our
      polymer scaffolds as a function of initial cell seeding density was established;
      we then investigated bone tissue formation throughout our scaffolds as a function
      of initial cell seeding density and time in culture. Initial cell seeding
      densities ranging from 0.5 to 10 x 10(6) cells/cm(3) were seeded onto 3D
      scaffolds. After 1 h in culture, we determined that 25% of initial seeded cells
      had adhered to the scaffolds in static culture conditions. The cell-seeded
      scaffolds remained in culture for 3 and 6 weeks, to investigate the effect of
      initial cell seeding density on bone tissue formation in vitro. Further cultures
      using 1 x 10(6) cells/cm(3) were maintained for 1 h and 1, 2, 4, and 6 weeks to
      study bone tissue formation as a function of culture period. After 3 and 6 weeks
      in culture, scaffolds seeded with 1 x 10(6) cells/cm(3) showed similar tissue
      formation as those seeded with higher initial cell seeding densities. When
      initial cell seeding densities of 1 x 10(6) cells/cm(3) were used, osteocalcin
      immunolabeling indicative of osteoblast differentiation was seen throughout the
      scaffolds after only 2 weeks of culture. Von Kossa and tetracycline labeling,
      indicative of mineralization, occurred after 3 weeks. These results demonstrated
      that differentiated bone tissue was formed throughout 3D scaffolds after 2 weeks
      in culture using an optimized initial cell density, whereas mineralization of the
      tissue only occurred after 3 weeks. Furthermore, after 6 weeks in culture, newly
      formed bone tissue had replaced degrading polymer.

PMID- 10880080
TI  - Development and in vitro characterization of vascular endothelial growth factor
      (VEGF)-loaded poly(DL-lactic-co-glycolic acid)/poly(ethylene glycol) microspheres
      using a solid encapsulation/single emulsion/solvent extraction technique.
AB  - Poly(DL-lactide-co-glycolide) (PLGA)/polyethylene glycol (PEG) microspheres are
      one modality of controlled delivery of biologically active molecules that would
      further the development of engineered tissues. As a possible mechanism to
      stimulate angiogenesis within an engineered tissue, vascular endothelial growth
      factor (VEGF) and bovine serum albumin (BSA) were coencapsulated into
      microspheres fabricated from PEG and 50/50 PLGA using a solid
      encapsulation/single-emulsion/solvent extraction technique. Two VEGF/BSA ratios
      were studied: 1:2000 and 1:10,000. Analysis consisted of the loading efficiency,
      particle size distribution, bright-field microscopy, scanning electron
      microscopy, release kinetics, and an in vitro human umbilical vein endothelial
      cell proliferation assay to assess biological activity of the released VEGF.
      Results show the microspheres could be manufactured, stored, and degraded over 28
      days. The burst release rates for 1:2000 and 1:10,000 VEGF/BSA microspheres were
      71.87 +/- 8.11 and 27.91 +/- 1.71 ng/mL (mean +/- standard error of the mean),
      respectively; steady-state release rates were 6.56 +/- 1.10 and 2.21 +/- 0.47
      ng/mL, respectively. The microspheres released biologically active VEGF, and the
      VEGF increased the proliferation of HUVECs in culture (p <.05). The successful
      development of a novel, cost-effective, scalable technique for producing
      microspheres loaded with biologically active proteins is presented. Using the
      data obtained from these studies, a defined concentration of microspheres will
      deliver a quantifiable level of VEGF at a known release rate.

PMID- 10880081
TI  - Enhanced guided bone regeneration by controlled tetracycline release from poly(L
      lactide) barrier membranes.
AB  - With the aim of providing effective periodontal therapeutic modality, drug
      releasing membranes for guided tissue regeneration (GTR) were developed. As GTR
      membranes, biodegradable barrier membranes composed of porous poly(L-lactide)
      (PLLA) films cast on poly(glycolide) (PGA) meshes were fabricated using an in-air
      drying phase inversion technique. PLLA was dissolved in methylene chloride
      ethylacetate mixtures, cast on knitted PGA mesh, and then air-dried.
      Tetracycline, which is used in periodontal therapy because of its antibacterial
      activity and tissue regenerating effects, including osteoblast chemotactic effect
      and anti-collagenolytic activity, was incorporated into the membranes by adding
      it to PLLA solutions. The guided bone regenerating potential of tetracycline
      loaded membranes was evaluated using release kinetics both in vitro and in vivo,
      biodegradation tests, and cell attachment tests. Homogeneous pores were generated
      both at the surface and in a sublayer of the membranes. The release kinetics of
      tetracycline depended mainly upon the hydrophilicity of tetracycline and the
      porosity of the membrane. The release rate further could be controlled by loaded
      drug contents. The release of tetracycline was appropriate for maintaining anti
      microbial activity and for its tissue-regenerating potential. The membranes
      retained a proper degradation property, maintaining their mechanical integrity
      for the barrier function for 4 weeks. Tetracycline-loaded membranes induced
      increased cell attachment levels compared with those of unloaded membranes.
      Tetracycline-loaded membranes markedly increased new bone formation in rat
      calvarial defects and induced bony reunion after 2 weeks of implantation. These
      results suggest that tetracycline-loaded PLLA membranes potentially enhance
      guided tissue regenerative efficacy.

PMID- 10880082
TI  - Anodic oxidation and hydrothermal treatment of titanium results in a surface that
      causes increased attachment and altered cytoskeletal morphology of rat bone
      marrow stromal cells in vitro.
AB  - Previous studies have suggested the usefulness of a new coating method-namely,
      the forming of a thin hydroxyapatite (HA) layer on commercially pure titanium
      (cpTi) by anodization and hydrothermal treatment-for use as a dental root implant
      material. In vivo and in vitro studies confirmed that an HA layer on cpTi
      (HA/cpTi) implants showed good compatibility with bone tissue, rat bone marrow
      stromal (RBM) cells, and immune cells. The aim of the present investigation was
      to further characterize the in vitro early cellular behavior of RBM cells on
      HA/cpTi implants. Therefore, in this study we performed surface analysis,
      analysis of cell initial attachment, and analysis of cell morphology and the
      cytoskeleton. Drops of distilled water or cell culture medium showed smaller
      contact angles with HA/cpTi than with cpTi. RBM cells were cultured for 30, 60,
      and 120 min on HA/cpTi and cpTi, and the level of cell adhesion was shown to
      increase with time on both substrates. However, cell adhesion on HA/cpTi was
      significantly higher than on cpTi at 60 and 120 min. Especially at 120 min, when
      compared with cpTi, the cell morphology on the surface of HA/cpTi not only
      adopted a flattened and spreading form, but also extended filopodium-like
      processes with irregular edges that were intimately adapted to the surface of the
      HA microcrystals. The cytoskeleton on HA/cpTi showed well-formed actin filaments
      that were parallel to each other and the long axis of RBM cells. The actin
      filaments of RBM cells on the HA/cpTi surface were localized to the periphery
      (corresponding to the edge of the filopodium-like processes) well after 120 min.
      This suggests that actin filaments of RBM cells need to be anchored at the
      HA/cpTi surface and the numerous HA microcrystals precipitated on the HA/cpTi
      surface. These findings were similar to the scanning electron microscopic
      morphology. The peripheral anchorage provide sufficient strength of attachment to
      allow recognization of actin filaments upon HA/cpTi. The surface of HA/cpTi was
      more hydrophilic and exhibited markedly improved wettability compared to
      untreated cpTi, and higher levels of early cell attachment were observed on
      surfaces after anodization and hydrothermal treatment than on surfaces with
      untreated cpTi. The results of in vitro experiments suggest that this new method
      for forming a thin HA layer on the surface of cpTi could be useful to ensure
      excellent cellular behavior on implant surfaces. The characterization of cell
      morphology on the thin HA layer formed by anodization and hydrothermal treatment
      on cpTi implant material suggests that physicochemical or biological conditioning
      of the implant surface involves implant surface topography.

PMID- 10880083
TI  - In vitro formation of oropharyngeal biofilms on silicone rubber treated with a
      palladium/tin salt mixture.
AB  - Adhesion of yeasts and bacteria to silicone rubber is one of the first steps in
      the biodeterioration of indwelling, silicone rubber voice prostheses. In this
      paper, silicone rubber, so-called "Groningen button," voice prostheses were
      treated with a colloidal palladium/tin solution to form a thin metal coat
      intended to discourage biofilm formation. First it was demonstrated that this
      treatment did not negatively affect the airflow resistance of the prostheses or
      induce any cytotoxicity. Subsequently, palladium/tin-treated voice prostheses
      were placed in a modified Robbins device together with untreated control
      prostheses to evaluate biofilm formation. Biofilms were formed by inoculating the
      device for 3 days with the total cultivable microflora obtained from an
      explanted, malfunctioning voice prosthesis supplemented with separately isolated
      yeasts (Candida albicans and Candida tropicalis). After 3 days the device was
      perfused three times daily with growth medium and phosphate-buffered saline. The
      device was allowed to drain between perfusions to better mimic the conditions in
      the oropharynx (moist but not always fully wetted). After 9 days the total number
      of bacterial and fungal colony-forming units on the prostheses were determined
      microbiologically, and scanning electron micrographs were taken of the valve
      sides. Biofilm formation was significantly less on the heavily treated
      palladium/tin prostheses than it was on the untreated prostheses although some
      ingrowing microcolonies also were observed on the treated prostheses. The spread
      of the biofilms was smaller on the treated prostheses than on the untreated ones.

PMID- 10880084
TI  - Synthesis, surface characterization, and platelet reactivity evaluation for the
      self-assembled monolayer of alkanethiol with sulfonic acid functionality.
AB  - Owing to the capability of fabricating a well-defined chemical structure on the
      surface, self-assembled alkanethiols with a variety of terminal functionalities
      were prepared on the gold substrate for investigating the interactions between
      the biological environment and synthetic surface. In this study, we report the
      synthesis of the sulfonic acid terminated long-chain alkanethiol, 10
      mercaptodecane-sulfonic acid, for direct preparation of a self-assembled
      monolayer (SAM) with -SO(3)H functionality. Nuclear magnetic resonance (NMR) and
      elemental analysis studies indicated that a high purity of sulfonic acid
      terminated alkanethiol was obtained. Surface characterization results showed that
      the -SO(3)H terminated SAM is hydrophilic and has a slightly higher hysteresis
      value, possibly because of the slower chain mobility of the bound sulfonic acid
      alkanethiol. Electron spectroscopy for chemical analysis (ESCA) analysis
      demonstrated that the -SO(3)H terminal group is situated in the outermost layer
      of the monolayer, as previous alkanethiol SAM structure models proposed. The
      platelet reactivity of the -SO(3)H SAM was higher than that of -OH SAM but less
      than the -CH(3) terminated one in vitro, whereas similar platelet reactivity was
      noticed between the -SO(3)H and -COOH SAMs. The higher platelet reactivity found
      on the -SO(3)H SAM could be caused by the higher surface functional group density
      inherent in the SAM structure and/or the composition and conformation state of
      the adsorbed protein layer.

PMID- 10880085
TI  - In vitro bioactivity and gentamicin release from glass-polymer-antibiotic
      composites.
AB  - Composite materials have been prepared from bioactive glass powders in the SiO(2)
      CaO-P(2)O(5) system, a biodegradable polymer [poly(L-lactic acid) (PLA)], a
      biostable polymer [polymethylmethacrylate (PMMA)], and an antibiotic
      [gentamicin]. The purpose of such composites is to obtain implantable materials
      that are able to lead to bone growth and also can, at the most critical
      inflammation-infection step, release an antibiotic. X-ray diffraction, scanning
      electron microscopy, X-ray energy dispersive spectroscopy, and FTIR analyses
      after different soaking periods in SBF demonstrated the growth of an apatite-like
      layer on the composite surface. Therefore the bioactive glass-polymer-antibiotic
      combination used in this work does not inhibit the glass bioactivity. The release
      of gentamicin after a soaking of the materials in SBF was followed by UV-visible
      spectroscopy. A fast initial release during the first 10 h of soaking, followed
      by a controlled release of the drug was observed.

PMID- 10880086
TI  - Attachment of astroglial cells to microfabricated pillar arrays of different
      geometries.
AB  - We studied the attachment of astroglial cells on smooth silicon and arrays of
      silicon pillars and wells with various widths and separations. Standard
      semiconductor industry photolithographic techniques were used to fabricate pillar
      arrays and wells in single-crystal silicon. The resulting pillars varied in width
      from 0. 5 to 2.0 micrometer, had interpillar gaps of 1.0-5.0 micrometer, and were
      1.0 micrometer in height. Arrays also contained 1.0-micromter-deep wells that
      were 0.5 micrometer in diameter and separated by 0.5-2.0 micrometer.
      Fluorescence, reflectance, and confocal light microscopies as well as scanning
      electron microscopy were used to quantify cell attachment, describe cell
      morphologies, and study the distribution of cytoskeletal proteins actin and
      vinculin on surfaces with pillars, wells, and smooth silicon. Seventy percent of
      LRM55 astroglial cells displayed a preference for pillars over smooth silicon,
      whereas only 40% preferred the wells to the smooth surfaces. Analysis of variance
      statistics performed on the data sets yielded values of p > approximately.5 for
      the comparison between pillar data sets and < approximately.0003 in the
      comparison between pillar and well data sets. Actin and vinculin distributions
      were highly polarized in cells found on pillar arrays. Scanning electron
      microscopy clearly demonstrated that cells made contact with the tops of the
      pillars and did not reach down into the spaces between pillars even when the
      interpillar gap was 5.0 microm. These experiments support the use of surface
      topography to direct the attachment, growth, and morphology of cells. These
      surfaces can be used to study fundamental cell properties such as cell
      attachment, proliferation, and gene expression. Such topography might also be
      used to modify implantable medical devices such as neural implants and lead to
      future developments in tissue engineering.

PMID- 10880087
TI  - Evaluation of the porcine intestinal collagen layer as a biomaterial.
AB  - The submucosal layer of the small intestine has been investigated as a source of
      collagenous tissue with the potential to be used as a biomaterial because of its
      inherent strength and biocompatibility. In this study we utilized a novel method
      for processing the tissue to generate an acellular intestinal collagen layer
      (ICL). This nondetergent, nonenzymatic chemical cleaning protocol removes cells
      and cellular debris without damaging the native collagen structure. Multilayer
      laminates of ICL crosslinked with a water-soluble carbodiimide (EDC) were
      evaluated as a tissue repair material in a rabbit abdominal hernia model. The ICL
      laminates provided the requisite physical properties and did not lead to adhesion
      formation. No immune response to the porcine collagen was detectable, and this
      material did not show any calcification in either the rabbit model or in the
      juvenile rat model.

PMID- 10880088
TI  - Fatigue characterization of a hydroxyapatite-reinforced polyethylene composite.
      I. Uniaxial fatigue.
AB  - The fatigue behavior of 40 volume % hydroxyapatite-reinforced polyethylene
      composite (HAPEXtrade mark) at 37 degrees C in saline was determined. S-N curves
      for this material, both in fully reversed axial tension-compression and fully
      reversed torsion, have been established. In tension, the cycles to failure ranged
      from 1000 cycles at 13 MPa to more than 1 million cycles at 4.4 MPa while in
      torsion they ranged from 100 cycles at 14.4 MPa to more than 1 million cycles at
      4.8 MPa. Changes in strain range, tangent modulus, and cyclic energy dissipated
      during fatigue loading also were examined. Torsional fatigue was found to be
      considerably more damaging than axial fatigue. The fatigue damage accumulation
      process occurring in the composite was monitored by observing the reduction in
      modulus and the increase in energy dissipated.

PMID- 10880089
TI  - Fatigue characterization of a hydroxyapatite-reinforced polyethylene composite.
      II. Biaxial fatigue.
AB  - Previously, the uniaxial fatigue behavior of 40 volume % hydroxyapatite
      reinforced polyethylene composite (HAPEXtrade mark) at 37 degrees C in saline was
      studied. Fatigue limits between 37 and 25% of the ultimate strengths of the
      material were established. This study investigates the biaxial fatigue behavior
      of the same material using various combinations of axial and torsional stresses.
      The addition of torsional to axial loading significantly reduced the fatigue
      life. When torsion at 25% of the ultimate strength was applied in addition to
      axial loading at 25% of the ultimate tensile strength, the fatigue life remained
      more than 1 million cycles. Out-of-phase loading was less detrimental to the
      fatigue life of the composite than in-phase. Fatigue damage was monitored by
      hysteresis loops, the increase in dissipated energy, the reduction in tangent
      modulus, and the increase in strain values.

PMID- 10880090
TI  - Dental restorative biomaterials induce glutathione depletion in cultured human
      gingival fibroblast: protective effect of N-acetyl cysteine.
AB  - Eight biomaterials eluted from four different types of dental restorative
      biomaterials, that is, from glass-ionomer cement (GIC: Ketac-fil and Fuji II),
      resin-modified glass ionomer cement (RM-GIC: Fuji II LC and Photac-fil),
      composite (Z100 MP and Tetric-flow), and compomer (Compoglass F and F-2000), were
      studied for their cytotoxic properties in relation to glutathione (GSH) content
      in cultured human gingival fibroblasts. Z100 MP, Tetric-flow, and Compoglass F
      were less cytotoxic than the others, with a toxic concentration of 50% (TC 50) >
      24% (of eluate), as determined by the MTT test. F-2000, Tetric-flow, and the
      other biomaterials were relatively more cytotoxic (TC 50 = 9-16%). With the
      exception of Z100 MP, all the biomaterials induced a depletion of cellular
      glutathione (GSH) that was variable depending upon the biomaterial eluates. The
      strongest GSH depletion was with F-2000, Fuji II, and Photac-fil. GSH depletion,
      with Compoglass and F-2000, was rapid-detectable after one h of cell treatment
      and complete within 3 h-whereas a longer period of incubation was required for
      the other biomaterials. Interestingly, the drug cytotoxic effects induced by all
      the biomaterials were prevented by cell treatment with the antioxidant N
      acetylcysteine (NAC). This study provides evidence that the cytotoxic property of
      dental restorative biomaterials is associated with depletion of the glutathione
      level in gingival fibroblasts. While the molecular mechanisms of this phenomenon
      require further investigations, our data suggest that NAC may be useful in
      preventing the cellular damage induced by dental restorative biomaterials.

PMID- 10880091
TI  - Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics.
AB  - Osteoblast, fibroblast, and endothelial cell adhesion on nanophase (that is,
      materials with grain sizes less than 100 nm) alumina, titania, and hydroxyapatite
      (HA) was investigated using in vitro cellular models. Osteoblast adhesion was
      significantly (p < 0.01) greater after 4 h on nanophase alumina, titania, and HA
      than it was on conventional formulations of the same ceramics. In contrast,
      compared to conventional alumina, titania, and HA, after 4 h fibroblast adhesion
      was significantly (p < 0.01) less on nanophase ceramics. Examination of the
      underlying mechanism(s) of cell adhesion on nanophase ceramics revealed that
      these ceramics adsorbed significantly (p < 0.01) greater quantities of
      vitronectin, which, subsequently, may have contributed to the observed select
      enhanced adhesion of osteoblasts. Select enhanced osteoblast adhesion was
      independent of surface chemistry and material phase but was dependent on the
      surface topography (specifically on grain and pore size) of nanophase ceramics.
      The capability of synthesizing and processing nanomaterials with tailored
      (through, for example, specific grain and pore size) structures and topographies
      to control select subsequent cell functions provides the possibility of designing
      the novel proactive biomaterials (that is, materials that elicit specific,
      timely, and desirable responses from surrounding cells and tissues) necessary for
      improved implant efficacy.

PMID- 10880092
TI  - Bacteriostatic action of a novel four-component bioactive glass.
AB  - Bacterial adhesion to biomaterials causing biomaterial-centered infection and
      poor tissue integration is a problem that limits the extensive use of many
      biomaterial devices in clinical applications. Bioactive materials are those
      biomaterials that form a compliant, mechanically stable bond with host tissue.
      Sol-gel-derived glasses in the three-component system SiO(2)-CaO-P(2)O(5) exhibit
      bioactivity that is dependent on composition and texture (i.e., specific surface
      area, pore size, structure, and distribution). The in vitro bioactivity and
      antibacterial action of a novel sol-gel-derived glass, AgBG, in the system SiO(2)
      CaO-P(2)O(5)-Ag(2)O are compared with those of its three-component counterpart,
      BG. The incorporation of 3-wt % Ag(2)O conferred antimicrobial properties to the
      glass without compromising its bioactivity. AgBG exhibited a marked
      bacteriostatic effect on E. coli MG1655 with a minimum inhibiting concentration
      of 0.2 mg (biomaterial)/mL (culture solution), above which bacterial growth was
      reduced to 0.01% of that of the control culture. In comparison, BG did not
      possess antimicrobial properties over the concentration range investigated (0.1
      40.0 mg/mL).

PMID- 10880093
TI  - Effects of geometry of hydroxyapatite as a cell substratum in BMP-induced ectopic
      bone formation.
AB  - Three different types of porous hydroxyapatite with pore sizes of 100-200
      micrometer in diameter-porous particles of hydroxyapatite (PPHAP), porous blocks
      of hydroxyapatite (PBHAP), and honeycomb-shaped hydroxyapatite (HCHAP)-were
      compared in terms of their abilities to induce osteogenesis when implanted
      subcutaneously with recombinant human BMP-2 into rats and extracted at 1, 2, 3,
      and 4 weeks. Histologically, direct bone formation occurred in PPHAP and PBHAP
      while only endochondral ossification took place in HCHAP. Interestingly,
      cartilage in the central zones and bone in the orifice zones of the tunnels of
      the HCHAP were observed at 2 weeks. After 3 weeks, the cartilage disappeared and
      bone formation occurred throughout the inner surface of the tunnels of the HCHAP,
      always leaving space for capillaries within the tunnels. Alkaline phosphatase
      activity and osteocalcin content were the highest in HCHAP among the three
      hydroxyapatite implants. These results clearly indicate that BMP-induced bone
      formation is highly dependent on the geometry of the carrier, which provides
      feasible structural factors for vascularization.

PMID- 10880094
TI  - Chitosan film enriched with an antioxidant agent, taurine, in fenestration
      defects.
AB  - A natural polysaccharide, chitosan (poly-N-acetyl glucosaminoglycan), which is a
      nontoxic and bioabsorbable polymer, has been shown to have hemostatic and
      antibacterial effects. An amino acid, taurine, is considered to be beneficial for
      regulating the inflammation process. The purpose of this study was to investigate
      the synergistic effects of taurine and chitosan in the experimental defects at
      the vestibular bone of maxillary canine teeth in six dogs. Chitosan films were
      prepared as delivery system with or without taurine and placed in the randomly
      chosen defects. Biopsies were performed on the postoperative seventh day and
      routine histological procedures were performed for light and electron microscopic
      evaluations. For each group, 30 different microscopic areas were examined and the
      numbers of macrophages and neutrophils in these areas were counted. The mean
      numbers of both macrophages and neutrophils were found statistically different
      between the chitosan film incorporated with taurine and free chitosan groups (p <
      0.0001 p > 0.05). In addition to the increase in cell counts in both groups, the
      cytological alterations were more obvious in the chitosan film group incorporated
      with taurine. Accordingly, taurine appears to enhance the acceleration effect of
      chitosan on wound healing at early periods. This effect could be considered
      beneficial in tissue repair in destructive diseases like periodontitis.

PMID- 10880095
TI  - Calculation of porosity and osteonal cement line effects on the effective
      fracture toughness of cortical bone in longitudinal crack growth.
AB  - Based on the microscopic analyses of cracks and correlational studies
      demonstrating evidence for a relationship between fracture toughness and
      microstructure of cortical bone, an equation was derived for bone fracture
      toughness in longitudinal crack growth, using debonding at osteonal cement lines
      and weakening effect of pores as main crack mechanisms. The correlation between
      the measured and predicted values of fracture toughness was highly significant
      but weak for a single optimal value of matrix to cement line fracture toughness
      ratio. Using fracture toughness values and histomorphometrical parameters from an
      available data set, matrix to cement line fracture toughness ratio was calculated
      for human femoral bone. Based on these calculations it is suggested that the
      effect of an osteon on fracture toughness will depend on the cement line's
      ability to compensate for the pore in an osteon. Matrix to cement line fracture
      toughness ratio significantly increased with increasing age, suggesting that the
      effectiveness of osteons in energy absorption may be reduced in the elderly due
      to a change in cement line properties.

PMID- 10880096
TI  - The polarity and magnitude of ambient charge influences three-dimensional neurite
      extension from DRGs.
AB  - Sulfated proteoglycans have inhibitory effects on neurite extension, and the
      negative charge of the glycosaminoglycan side chains may be involved in the
      inhibitory process. The main goal of this study is to investigate the effects of
      charge on three-dimensional neurite extension. Various concentrations of dermatan
      sulfate (DS), a chondroitin sulfate glycosaminoglycan, and consequently, various
      degrees of negative charge were presented on three-dimensional agarose hydrogels
      and the effect of charge on neurite extension from primary neurons was
      investigated. Dose-response experiments were also performed with the polycationic
      (positively charged) polysaccharide chitosan covalently coupled to agarose. The
      amount of DS or chitosan coupled to the agarose gel was quantified via
      metachromatic dye or Fourier transform infrared spectroscopy methods,
      respectively. The length of embryonic day 9 (E9) chick dorsal root ganglia
      neurites extended through charged agarose gels is dependent on the polarity and
      quantity of ambient charge. The inhibitory effects of the sulfated DS and the
      enhancing effects of the polycationic chitosan on neurite extension decrease as
      the amount of DS or chitosan coupled to agarose is decreased. These findings
      indicate that primary neural process extension is influenced by the polarity of
      ambient charge in a dose-responsive manner.

PMID- 10880097
TI  - Surface microarchitectural design in biomedical applications: in vivo analysis of
      tissue ingrowth in excimer laser-directed micropored scaffold for cardiovascular
      tissue engineering.
AB  - A micropatterned microporous segmented polyurethane film (20 x 12 mm in size, 30
      micrometer thick) with four regions was prepared by excimer laser microprocessing
      to provide an in vivo model of transmural tissue ingrowth in an open cell
      structured scaffold specially designed for cardiovascular tissue engineering.
      Three microporous regions had the same circular micropores (30 micrometer
      diameter) but different pore density arrangements (percentage of total pore area
      against unit area was 0.3%, 1.1%, and 4.5%), and the other region remained
      nonporous. The covered stent, prepared by wrapping the regionally different
      density-microporous film on an expandable metallic stent (approximately 3.1 mm in
      diameter), was delivered to the luminal surface of canine common carotid arteries
      and placed after expansion of the stent to a diameter of approximately 8 mm using
      a balloon catheter. At 4 weeks of implantation, all the covered stents (n = 10)
      were patent. The luminal surfaces of the covered stents were almost confluently
      endothelialized both in nonporous and microporous regions. Histological
      examination showed that the neointimal wall was formed by tissue ingrowth from
      host through micropores (transmural) and anastomotic sites. Thrombus formation
      occurred frequently in the lowest density porous region and nonporous region.
      With an increase in pore density, the thickness of the neointimal wall decreased.
      This study demonstrated how the micropore density of implanted devices influences
      tissue ingrowth in arterial implantation.

PMID- 10880098
TI  - Early spreading events of fibroblasts on microgrooved substrates.
AB  - We investigated the "contact guidance" phenomenon, shortly after cell attachment.
      For this purpose polystyrene substrates were produced, either smooth, or equipped
      with micogrooves (depth 0.5 micrometer, width 1-10 micrometer). On these
      substrates, fibroblasts were cultured for 15, 30, 45, 60, 120, or 240 min.
      Subsequently, they were studied with light microscopy, scanning electron
      microscopy, confocal laser scanning microscopy, and digital image analysis. Up to
      1 h, cell attachment on the grooved substrates was impaired. Further, cells
      oriented to the direction of the microgrooves. This orientation was established
      fastest on the narrow grooves. After 30 min, cells showed abundant membrane
      extensions in all directions. Well-formed actin filaments were not present in the
      cell body at timepoints before 4 h. Furthermore, cells on smooth surfaces
      exhibited less filaments. The addition of cytochalasin-B only caused a delay of
      cell attachment and spreading. From these experiments, we conclude that a well
      formed cellular actin cytoskeleton is no prerequisite for the occurrence of
      contact guidance. Actin microfilaments in the lamellipodia, and the interplay
      between the lamellipodium and extracellular matrix molecules seem to be the
      determining factor in the establishment of contact guidance.

PMID- 10880099
TI  - Plasma-treated PET surfaces improve the biocompatibility of human endothelial
      cells.
AB  - Failures of small internal diameter vascular grafts have been caused by the lack
      of a stable endothelial lining to form on their artificial surfaces. Polymer
      surfaces can be optimized by means of proper treatment to allow a homogeneous and
      uniform coverage in artificial prosthesis applications. Several solutions were
      studied to improve cell attachment and growth on artificial materials. In the
      present study, polyethyleneterephthalate (PET) surfaces were treated by plasma
      processes with oxygen and ammonia and also in the presence of a gas mixture to
      verify the effect of functional groups grafting onto the endothelial cell growth.
      Related surface chemical modifications were investigated by X-ray photoelectron
      spectroscopy (XPS). Then using cytotoxicity and cytocompatibility tests, the
      biocompatibility of the modified PET surfaces was assessed by studying the
      behavior of human umbilical vein endothelial cells (HUVEC). The results showed
      that plasma-treated PET samples have no toxic effect on HUVEC. The
      cytocompatibility tests revealed an increase in cell growth with incubation time
      and the presence of well-spread and flattened cells (SEM analyses). Thus it is
      reported that plasma treatments can improve PET biocompatibility to HUVEC.

PMID- 10880100
TI  - Mechanisms of cell activation by metal ions: influence of pH.

PMID- 10880101
TI  - The kinetics of 1,4-butanediol diglycidyl ether crosslinking of dermal sheep
      collagen.
AB  - Dermal sheep collagen was crosslinked with 1,4-butanediol diglycidyl ether
      (BDDGE) or modified with glycidyl isopropyl ether (PGE). The reduction in amine
      groups as a function of time was followed to study the overall reaction kinetics
      of collagen with either BDDGE or PGE. Linearization of the experimental data
      resulted in a reaction order of 2 with respect to the amine groups in the PGE
      masking reaction, whereas a reaction order of 2.5 was obtained in the BDDGE
      crosslinking reaction. The reaction orders were independent of the pH in the
      range of 8.5-10.5 and the reagent concentration (1-4 wt %). The reaction order
      with respect to epoxide groups was equal to 1 for both reagents. As expected, the
      reaction rate was favored by a higher reagent concentration and a higher solution
      pH. Because the BDDGE crosslinking reaction occurs via two distinct reaction
      steps, the content of pendant epoxide groups in the collagen matrix was
      determined by treating the collagen with either O-phosphoryl ethanolamine or
      lysine methyl ester. The increase in either phosphor or primary amine groups was
      related to the content of pendant groups. Crosslinking at pH 9.0 resulted in a
      low reaction rate but in a high crosslink efficacy, especially after prolonged
      reaction times. A maximum concentration of pendant epoxide groups was detected
      after 50 h. Reaction at pH 10.0 was faster, but a lower crosslinking efficacy was
      obtained. At pH 10.0, the ratio between pendant epoxide groups and crosslinks was
      almost equal to 1 during the course of the crosslinking reaction.

PMID- 10880102
TI  - Modification of inflammatory response to implanted biomedical materials in vivo
      by surface bound superoxide dismutase mimics.
AB  - The healing response to implanted biomedical materials involves varying degrees
      and stages of inflammation and healing which in some cases leads to device
      failure. In this article, we describe synthetic methods and in vivo results of a
      novel surface treatment for biomedical materials involving covalent conjugation
      of a low molecular weight superoxide dismutase mimic (SODm), which imparts anti
      inflammatory character to the material. SODm investigated in this study are a new
      class of anti-inflammatory drugs consisting of a Mn(II) complex of a macrocyclic
      polyamine ring that catalyze the dismutation of superoxide at rates equivalent to
      that of native enzyme. The SODms were covalently linked to small disks of ultra
      high molecular weight polyethylene, poly(etherurethane urea), and tantalum metal
      at two concentrations and implanted in a subcutaneous rat implant model for 3, 7,
      14, and 28 days. Histological examination of the implant tissue performed at 3
      and 28 days revealed striking anti-inflammatory effects on both acute and chronic
      inflammatory responses. At 3 days, the formation of a neutrophil-rich acute
      inflammatory infiltrate seen in control implants was inhibited for all three
      materials treated with SODm. At 28 days, foreign body giant cell formation
      (number of FBGCs per field) and fibrous capsule formation (mean thickness of
      implant capsule) were also significantly inhibited over untreated control
      implants. A mechanism based on our current understanding of superoxide as an
      inflammatory mediator at implanted biomedical materials is proposed.

PMID- 10880103
TI  - Biocompatibility of alloys used in orthodontics evaluated by cell culture tests.
AB  - The cytotoxicity of the most common alloys used in orthodontic appliances was
      determined by cell culture testing. Human gingival fibroblasts were cultured on
      304 and 316 stainless steel, on brazing alloy composed of palladium (Pd), copper
      (Cu), and silver (Ag), and on plastic substrate (control). Studies were carried
      out with SEM and radiolabeled precursor incorporation. Cells were cultured in MEM
      without serum but with the addition of (3)H-thymidine to evaluate cell
      proliferation and (3)H-glucosamine to evaluate glycosaminoglycan (GAG) synthesis
      and secretion in the culture medium. Moreover, gingival fibroblasts were cultured
      in the presence of some metal ions generally released by orthodontic appliances
      to evaluate the cytotoxic effects of single ions. Morphologic observations with
      SEM and radiolabeled incorporation studies showed that 304 and 316 stainless
      steel were more biocompatible than the brazing alloy. Among the metal ions
      tested, Ag and Pd, constituents of the brazing alloy, showed the highest
      cytotoxicity.

PMID- 10880104
TI  - Effect of self-etching primers containing N-acryloyl aspartic acid on dentin
      adhesion.
AB  - The purpose of this study was to evaluate the feasibility of aspartic acid
      derivative, N-acryloyl aspartic acid (N-AAsp) when used as a self-etching primer
      prior to the application of a commercial bonding agent containing 10
      methacryloxydecyl dihydrogen phosphate. N-AAsp was synthesized by the reaction of
      DL-aspartic acid and acryloyl chloride. N-AAsp can be dissolved in water up to 25
      wt % and can adequately remove the smear layer. When 20 wt % N-AAsp was applied
      as a self-etching primer, the tensile bonding strength of resin composite to
      dentin doubled to 16.0 MPa compared with that of the nonetching group or the 40
      wt % H(3)PO(4) etching/water rinse group. Scanning electron microscopic
      observations revealed that the formation of the hybrid layer at the interface
      between the resin composite and dentin and the thickness of the hybrid layer
      increased with N-AAsp concentration. The hybrid layer in the specimens treated
      with 20 wt % N-AAsp aqueous solution presented a uniform structure, whereas those
      treated with 5 wt % N-AAsp solution showed a porous structure. We conclude that
      20 wt % N-AAsp aqueous solution has good potential value as a self-etching
      primer.

PMID- 10880105
TI  - In vivo and in vitro degradation of poly[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon
      CL], and the implications for the use in nerve reconstruction.
AB  - Nerve guides can be used for the reconstruction of peripheral nerve defects.
      After serving their function, nerve guides should degrade. p[(50)/(50)
      ((85)/(15)(L)/(D))LA/epsilon-CL] degrades completely within 1 year without the
      formation of a slow degrading crystalline fraction. Although the tensile strength
      (TS) of a p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] nerve guide is negligible
      after 2 months, nerve regeneration across a 1-cm gap in the sciatic nerve of the
      rat is faster and qualitatively better than after reconstruction using autologous
      nerve grafts. During degradation p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL]
      swells, especially during the first 3 months. This can have a negative influence
      on the regenerating nerve. p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] nerve
      guides could only be used in the clinical situation in case of short nerve gaps
      (several mm) in small nerves (for instance digital nerves). Refinements will be
      needed to successfully reconstruct longer nerve gaps (several cm).

PMID- 10880106
TI  - Chitosan supports the expression of extracellular matrix proteins in human
      osteoblasts and chondrocytes.
AB  - The search for biocompatible materials that can support the growth and phenotypic
      expression of osteoblasts and chondrocytes is a major challenge in the
      application of tissue engineering techniques for the repair of bone and cartilage
      defects. Chitosan, a copolymer of glucosamine and N-acetylglucosamine, may
      provide an answer to this search. Chitosan is the deacetylated product of chitin,
      a ubiquitous biopolymer found in the exoskeleton of insects and marine
      invertebrates. Little is known about the utility of chitosan in propagating human
      osteoblasts and chondrocytes. In this study, we test the hypothesis that chitosan
      promotes the survival and function of osteoblasts and chondrocytes. Chitosan (4%,
      w/v in 2% HAc) was coated onto plastic coverslips that had been fitted into 24
      well plates. Human osteoblasts and articular chondrocytes were seeded on either
      uncoated or chitosan-coated coverslips at 1 x 10(5)/cells per well. Cultures were
      incubated at 37 degrees C, 5% CO(2) for a period of 7 days. Cell viability was
      assessed at that time using a fluorescent molecular probe. The phenotypic
      expression of osteoblasts and chondrocytes was analyzed by reverse transcriptase
      polymerase chain reaction and immunocytochemistry. Osteoblasts and chondrocytes
      appeared spherical and refractile on chitosan-coated coverslips. In contrast,
      greater than 90% of cells on plastic coverslips were elongated and spindle shaped
      after 7 days of culture. Similar to cells propagated on uncoated control wells,
      greater than 90% of human osteoblasts and chondrocytes propagated on chitosan
      remained viable. Human osteoblasts propagated on chitosan films continued to
      express collagen type I whereas chondrocytes expressed collagen type II and
      aggrecan, as shown by reverse transcriptase-polymerase chain reaction analysis
      and immunostaining. The present in vitro work demonstrates the biocompatibility
      of chitosan as a substrate for the growth and continued function of human
      osteoblasts and chondrocytes. Chitosan may have potential use as a tissue
      engineering tool for the repair of osseous and chondral defects.

PMID- 10880107
TI  - Bioactive glass serves as a substrate for maintenance of phenotype of nucleus
      pulposus cells of the intervertebral disc.
AB  - The objective of the study was to investigate the capability of bioactive glass
      45S5 to serve as a substrate for nucleus pulposus cells in vitro. Nucleus
      pulposus cells were isolated from adult rabbit discs and seeded onto bioactive
      glass. At selected time intervals, the cells and glass were evaluated. We found
      that the cells rapidly attached to the substrate, colonizing it within 12 h. By
      21 days, they had formed a lawn of cells over the glass substrate. DNA
      measurements showed a progressive increase in cell number with time. The
      phenotype was maintained; the cells expressed aggrecan, and collagen type II and
      I, but were negative for collagen type X. CD44, a cell-surface glycoprotein that
      binds hyaluronate, was also expressed by these cells. Electron dispersive X-ray
      analysis and Fourier transform infrared spectroscopy revealed calcium phosphate
      rich layer formation on the substrate surface. The results of this study suggest
      that nucleus pulposus cell proliferation may be an anchorage dependent event, and
      that the cells use the calcium phosphate-rich layer to facilitate cell adhesion,
      and subsequent proliferation. These findings point to the importance of the
      conditioned bioactive glass as a substrate for nucleus pulposus cells.

PMID- 10880108
TI  - Bioactivity and mechanical properties of PDMS-modified CaO-SiO(2)-TiO(2) hybrids
      prepared by sol-gel process.
AB  - Hydrolysis and polycondensation of poly(dimethylsiloxane) (PDMS),
      tetraethoxysilane (TEOS), tetraisopropyltitanate (TiPT), and calcium nitrate gave
      essentially pore- and crack-free transparent monolithics of PDMS-modified CaO
      SiO(2)-TiO(2) hybrids, when PDMS/(TEOS + TiPT) was larger than 26:74 in weight,
      under constant ratios of TEOS/TiPT of 9:1 in mol and Ca/(TEOS + TiPT) of 0.15 in
      mol. Their apatite-forming abilities in a simulated body fluid, which is
      indicative of bioactivity, increased with decreasing PDMS/(TEOS + TiPT). Their
      extensibility and Young's modulus decreased and increased, respectively, with
      decreasing PDMS/(TEOS + TiPT). The hybrids with PDMS/(TEOS + TiPT) of about 30:70
      in weight showed fairly high apatite-forming ability, high extensibilities, and
      Young's moduli almost equal to those of the human cancellous bones. These new
      kind of bioactive materials with unique mechanical properties may be useful as
      bone-repairing materials.

PMID- 10880110
TI  - Laminin-coated poly(L-lactide) filaments induce robust neurite growth while
      providing directional orientation.
AB  - Cellular channels during development and after peripheral nerve injury are
      thought to provide guidance cues to growing axons. In tissue culture where these
      cues are absent, neurites from dorsal root ganglion neurons grow with a radial
      distribution. To induce directional axonal growth and to enhance the rate of
      axonal growth after injury, we have designed microfilaments of poly(L-lactide).
      We demonstrate that dorsal root ganglia grown on these filaments in vitro extend
      longitudinally oriented neurites in a manner similar to native peripheral nerves.
      The extent of neurite growth was significantly higher on laminin-coated filaments
      compared with uncoated and poly-L-lysine-coated filaments. As high as 5.8 +/- 0.2
      mm growth was observed on laminin-coated filaments compared with 2.0 +/- 0.2 mm
      on uncoated and 2.2 +/- 0.3 mm on poly-L-lysine-coated filaments within 8 days.
      Schwann cells were found to grow on all types of filaments. They were, however,
      absent in the leading edges of growth on laminin-coated filaments. Photolysis of
      Schwann cells caused a significant reduction in the neurite length on all types
      of filaments. Laminin-coated filaments, however, induced significantly longer
      neurites compared with uncoated and/or poly-L-lysine-coated filaments even in the
      absence of Schwann cells. Our results suggest that laminin-coated poly(L-lactide)
      filaments are suitable for inducing directional and enhanced axonal growth.
      Implants designed by arranging these microfilaments into bundles should aid
      regenerating axons by providing guidance cues and channels to organize matrix
      deposition, cell migration, axon growth, and improve functional recovery.

PMID- 10880109
TI  - Peptoid-containing collagen mimetics with cell binding activity.
AB  - Collagen mimetic peptides containing the peptoid residue Nleu (Goodman
      Bhumralkar, Jefferson, Kwak, Locardi. Biopolymers 1998;47:127-142) were tested
      for interactions with epithelial cells and fibroblasts. Molecules containing the
      sequence Gly-Pro-Nleu with a minimum of nine repeats showed cell binding
      activity. The activity of these molecules appeared to be conformationally
      sensitive, with the triple-helical form being preferred. When immobilized on a
      surface, the (Gly-Pro-Nleu)(10)-Gly-Pro-NH(2) sequence stimulated the attachment
      and growth of corneal epithelial cells and fibroblasts and the migration of
      epithelial tissue. The peptide sequence KDGEA inhibited cell attachment to the
      (Gly-Pro-Nleu)(10)-Gly-Pro-NH(2) sequence, suggesting that cell binding to this
      collagen mimetic involves the alpha2beta1 heterodimer integrin receptor.
      Interestingly, peptides containing the sequence (GlyNleu-Pro-)(10)-NH(2) did not
      have cell binding activity. The discovery that triple-helical peptides containing
      the Gly-Pro-Nleu sequences interact with cells opens up new opportunities in the
      design of collagen mimetic biomaterials.

PMID- 10880111
TI  - Biodegradable scleral implant for controlled intraocular delivery of
      betamethasone phosphate.
AB  - We evaluated nail-like, biodegradable scleral implants as a controlled
      intraocular delivery system of betamethasone phosphate (BP) for the treatment of
      chronic uveitis using pigmented rabbits. The scleral implants, which contained
      10% and 25% of BP (weight 8.5 mg; length 5 mm), were made of poly (D,L-lactide-co
      glycolide) (PLGA). In vivo release and retinal toxicity after implantation were
      also studied in pigmented rabbits. The in vitro release studies demonstrated the
      10% and 25% BP-loaded scleral implants released BP in a biphasic release pattern
      for at least 1 month. The BP concentrations in the vitreous and the
      retina/choroid after application of scleral implants in pigmented rabbit eyes
      stayed within the concentration range capable of suppressing inflammatory
      responses for over 1 month. The BP concentration was greater in the
      retina/choroid than in the vitreous throughout the study. No substantial toxic
      reactions in the retina were observed by electroretinography. Our findings
      suggest that the BP-loaded scleral implant may be a promising device for
      treatment of chronic uveitis.

PMID- 10880112
TI  - Comparative study of seeding methods for three-dimensional polymeric scaffolds.
AB  - Development of tissue-engineered devices may be enhanced by combining cells with
      porous absorbable polymeric scaffolds before implantation. The cells are seeded
      throughout the scaffolds and allowed to proliferate in vitro for a predetermined
      amount of time. The distribution of cells throughout the porous material is one
      critical component determining success or failure of the tissue-engineered
      device. This can influence both the successful integration of the device with the
      host tissue as well as the development of a vascularized network throughout the
      entire scaffold volume. This research sought to compare different seeding and
      proliferation methods to select an ideal method for a polyglycolide/aortic
      endothelial cell system. Two seeding environments, static and dynamic, and three
      proliferation environments, static, dynamic, and bioreactor, were analyzed, for a
      total of six possible methods. The six seeding and proliferation combinations
      were analyzed following a 1-week total culture time. It was determined that for
      this specific system, dynamic seeding followed by a dynamic proliferation phase
      is the least promising method and dynamic seeding followed by a bioreactor
      proliferation phase is the most promising.

PMID- 10880113
TI  - Experimental studies on the nature of property gradients in the human dentine.
AB  - We conducted an investigation into the nature of dentine mineralization and
      mechanical property gradients with the aid of experimental techniques such as the
      fluoroscopic X-ray microanalysis and instrumented microindentation, respectively.
      It was found that the tooth adapts to a complex structure with significant
      gradients in properties. We observed a significant correlation between the degree
      of mineralization within the dentine and the mechanical properties. The natural
      gradation in mechanical properties is explained by the stress analysis within
      anatomical-sized tooth specimens done using digital photoelasticity. These
      results are explained within the context of the functional requirements that are
      imposed on the tooth. This study highlights tooth structure as a biologically
      adapted, functionally graded material.

PMID- 10880114
TI  - Structural study and stability of hydroxyapatite and beta-tricalcium phosphate:
      two important bioceramics.
AB  - The stability of hydroxyapatite (OHAP) and beta-tricalcium phosphate (beta-TCP)
      ceramics depends on the temperature of preparation and the partial pressure of
      water in the reaction atmosphere. In bioceramics used in the study of
      biomaterials, these two phosphates often coexist in distinct proportions;
      therefore, structural characterization of the individual phases is hindered. The
      structure of these two individual calcium phosphates have been studied using X
      ray diffraction, and mainly by high-resolution electron microscopy. Whereas the X
      ray diffraction profile of OHAP has been refined in the space group P6(3)/m, the
      HREM images oriented along the [001] direction at the edges of the crystal show a
      threefold symmetry. The X-ray diffraction pattern of beta-TCP has been refined in
      the space group R3c and the HREM image oriented along [0001] zone axis shows
      regular contrast. Both these calcium phosphate ceramics are unstable to the
      electron beam for a prolonged exposure time, and show areas of decomposition in
      HREM images of thin regions of the crystal. The regions of decomposition in the
      beta-TCP crystal show the presence of CaO as one of the major phases.

PMID- 10880115
TI  - Platelet adhesion and procoagulant activity induced by contact with
      radiofrequency glow discharge polymers: roles of adsorbed fibrinogen and vWF.
AB  - The potential hemocompatibility of radiofrequency glow discharge (RFGD) polymers
      made by copolymerization of mixtures of hexafluoropropene and ethylene
      (C(3)F(6)/C(2)H(4)) or acrylic acid and 1,7-octadiene was investigated using in
      vitro assays for platelet adhesion and platelet catalyzed thrombin generation.
      Thrombin generation rate normalized to platelet number was used as a measurement
      of platelet activation (procoagulant activity). RFGD polymers produced by
      copolymerization of acrylic acid and 1, 7-octadiene contained varying amounts of
      carboxylic acid species as determined by electron spectroscopy for chemical
      analysis (ESCA). These polymers induced little variation in platelet adhesion,
      thrombin generation, or platelet activation. RFGD polymerization of C(3)F(6) and
      C(2)H(4) resulted in polymers with varying proportions of fluorinated species, as
      determined by ESCA. Fibrinogen adsorption from plasma was maximal on a polymer
      made with 25% C(3)F(6) (75% C(2)H(4)) in the feed. However von Willebrand factor
      (vWF) adsorption was greater on polymers made with increased %C(3)F(6) in the
      feed. Platelet adhesion decreased with increasing %C(3)F(6) in the feed. Thrombin
      generation was lowest for platelets adherent to polymers made from both C(3)F(6)
      and C(2)H(4). Therefore, procoagulant activity of platelets increased for
      polymers made with increased %C(3)F(6) in the feed, similar to the trend in vWF
      adsorption. These findings suggest that increased incorporation of fluorinated
      species into RFGD polymers leads to decreased platelet adhesion and increased
      platelet activation (which is possibly due to increased vWF adsorption).

PMID- 10880116
TI  - Biphasic calcium phosphates: influence of three synthesis parameters on the
      HA/beta-TCP ratio.
AB  - Hydroxyapatite (HA) contents measurements were conducted on eight biphasic
      calcium phosphate (BCP) samples obtained by sintering calcium-deficient apatite
      formed previously by hydrolyzing a dicalcium phosphate dihydrate (DCPD) powder.
      We evaluated the influences and interactions of three synthesis factors:
      alkalinity, process duration, and concentration of the water suspension in DCPD.
      Those parameters were varied simultaneously between two limit levels. Experiments
      used a factorial design method (FDM) allowing optimization of the number of
      samples as well as statistical analysis of results. FDM showed that HA content,
      in a defined experimental area, can be described by a first-order polynomial
      equation in which the initial alcalinity and the DCPD/water ratio are the major
      influences. Experiment prove that pH measured at the end of the hydrolysis was
      predictive of the HA content in the final BCP. This study leads up to an
      isoresponse line diagram which will allow the synthesis of some BCP with fitted
      HA/beta-tricalcium phosphate ratios.

PMID- 10880117
TI  - Effect of surface treatment and sterilization processes on the corrosion behavior
      of NiTi shape memory alloy.
AB  - Nickel-titanium (NiTi) alloy derives its biocompatibility and good corrosion
      resistance from a homogeneous oxide layer mainly composed of TiO(2), with a very
      low concentration of nickel. In this article, we described the corrosion behavior
      of NiTi alloys after mechanical polishing, electropolishing, and sterilization
      processes using cyclic polarization and atomic absorption. As a preparative
      surface treatment, electropolishing decreased the amount of nickel on the surface
      and remarkably improved the corrosion behavior of the alloy by increasing the
      mean breakdown potential value and the reproducibility of the results (0.99 +/-
      0.05 V/SCE vs. 0.53 +/- 0. 42). Ethylene oxide and Sterrad(R) sterilization
      techniques did not modify the corrosion resistance of electropolished NiTi,
      whereas a steam autoclave and, to a lesser extent, peracetic acid sterilization
      produced scattered breakdown potential. In comparing the corrosion resistance of
      common biomaterials, NiTi ranked between 316L stainless steel and Ti6A14V even
      after sterilization. Electropolished NiTi and 316L stainless-steel alloys
      released similar amounts of nickel after a few days of immersion in Hank's
      solution. Measurements by atomic absorption have shown that the amount of
      released nickel from passive dissolution was below the expected toxic level in
      the human body. Auger electron spectroscopy analyses indicated surface
      contamination by Ca and P on NiTi during immersion, but no significant
      modification in oxide thickness was observed.

PMID- 10880118
TI  - Controlling human polymorphonuclear leukocytes motility using microfabrication
      technology.
AB  - We describe a new approach for controlling cell motility on a material surface.
      Transparent, photosensitive polyimide materials were used to fabricate physical
      structures on glass; cell motility was then followed over time using optical
      microscopy. Arrays of pillars and holes with 2 micron square, 4-microm height (or
      depth) separated by 10 microm were successfully patterned using photolithography.
      Neutrophils attached and spread on the smooth glass surface and surfaces with
      pillars. In contrast, cells were rounded and did not adhere to either smooth
      polyimide film or films with holes. The migration of neutrophils was much faster
      on holes than on polyimide surface, but it was significantly slower on pillars
      than on glass. These results suggest that physical patterning may be an effective
      tool to manipulate cell migration in the design of biomaterials for tissue
      engineering.

PMID- 10880119
TI  - Three-dimensional cultivation of human osteoblast-like cells on highly porous
      natural bone mineral.
AB  - In this study, we investigated the growth and extracellular matrix synthesis of
      human osteoblast-like cells on highly porous natural bone mineral. Human bone
      cells were isolated from trabecular bone during routine iliac crest biopsies.
      Under conventional culture conditions, trabecular bone cells were able to assume
      the organization of a three-dimensional structure on a porous natural bone
      mineral (Bio-Oss(R) Block). Scanning electron microscopy examination after 6
      weeks revealed multiple cell layers on the trabecular block. Transmission
      electron microscopy examination after 6 weeks revealed the accumulation of mature
      collagen fibrils in the intracellular and extracellular spaces, and showed
      multilayered, rough endoplasmic reticulum as well as mitochondria-rich cells
      surrounded by dense extracellular matrix. These morphological observations
      suggest that the cell layer may resemble the natural three-dimensional structure.
      Biochemical analysis revealed that the hydroxylysylpyridinoline,
      lysylpyridinoline, and hydroxyproline content of the cell layer increased in a
      time-dependent manner, whereas in monolayer culture without natural bone mineral,
      no measurable amounts of hydroxylysylpyridinoline or lysylpyridinoline, and a
      barely measurable amount of hydroxyproline, were noted. Mature collagen extracted
      by ethylenediaminetetraacetic acid-demineralization from the cell layer on
      natural bone mineral showed an identical electrophoretic pattern to that observed
      in human bone, as evaluated by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis. The present study demonstrated an excellent biocompatibility of
      the highly porous natural bone mineral in a three-dimensional bone cell culture
      system, and thus its potential for tissue-engineered growth of human bone.

PMID- 10880120
TI  - In situ compressive properties of the glenoid labrum.
AB  - The purpose of this study was to measure the structural stiffness
      (load/displacement response) and elastic modulus (stress-strain response) of the
      glenoid labrum at different locations throughout the tissue. It was intended that
      the results of this work would serve to define the properties of the labrum. This
      in turn may permit a better understanding of labral function and of the mechanics
      of injury or degeneration and may ultimately contribute to improving the design
      of future labral reconstruction procedures. In addition, these data may allow
      incorporation of labral properties into a glenoid arthroplasty component. The
      testing procedure consisted of rapid compression of the labrum using a flat
      indentor. Stiffness and modulus results demonstrated differences between the
      superior and inferior portions of the labrum. The elastic moduli findings for the
      labrum were 0.18 +/- 0.17, 0.11 +/- 0.16, and 0.23 +/- 0.20 MPa for the inferior
      anterior, inferior, and inferior posterior sections, respectively. The superior
      anterior, superior, and superior posterior sections were respectively 0.19 +/-
      0.09, 0. 32 +/- 0.22, and 0.41 +/- 0.32 MPa. These results are similar to those
      of knee menisci. The modulus findings for the substrate cartilage were 1.92 +/-
      0.78, 1.99 +/- 0.70, and 2.00 +/- 1.33 MPa for the inferior anterior, inferior,
      and inferior posterior sections, respectively. The superior anterior, superior,
      and superior posterior sections were respectively 1.60 +/- 0.79, 1.29 +/- 0.75,
      and 1.42 +/- 0.54 MPa, which are comparable to previous cartilage findings.

PMID- 10880121
TI  - Low temperature formation of calcium-deficient hydroxyapatite-PLA/PLGA
      composites.
AB  - Hydroxyapatite-biodegradable polymer composites have been formed by a low
      temperature chemical route. Precomposite structures were prepared by combining
      alpha-Ca(3)(PO(4))(2) (alpha-tricalcium phosphate or alpha-TCP) with poly(L
      lactic) acid and poly(DL-lactide-co-glycolide) copolymers. The final composite
      structure was achieved by in situ hydrolysis of alpha-TCP to
      Ca(9)(HPO(4))(PO(4))(5)OH (calcium deficient hydroxyapatite or CDHAp) either in
      solvent cast or pressed precomposites. Hydrolysis was performed at 56 degrees C-a
      temperature slightly above the glass transition of the polymers. The effects of
      polymer chemistry, composite formation technique, and porosity on hydrolysis
      kinetics and degree of transformation were examined with isothermal calorimetry,
      X-ray diffraction (XRD), Fourier transform infrared spectroscopy, and scanning
      electron microscopy. Calorimetric data and XRD analyses revealed that hydrolysis
      reactions were inhibited in the presence of the polymers. Isothermal calorimetry
      indicated the extent of the alpha-TCP to CDHAp transformation in 24 h to be 85%
      in the solvent cast composites containing PLGA (85:15) copolymer; however, XRD
      analyses suggested almost complete reaction. The CDHAp formation extent was 26%
      for the pressed composites containing the same polymer. In the presence of NaCl
      as a pore generator, 81% transformation was observed for the pressed composites.
      This transformation occurred without any chemical reaction between the polymer
      inorganic components, as determined by Fourier transform infrared spectroscopy.
      Minimal transformation to CDHAp occurred in composites containing poly(L-lactic)
      acid.

PMID- 10880122
TI  - Calcium-deficient hydroxyapatite-PLGA composites: mechanical and microstructural
      investigation.
AB  - The microstructural and mechanical properties of composites composed of calcium
      deficient hydroxyapatite (CDHAp) and poly(lactide-co-glycolide) (PLGA) have been
      investigated. The composites were formed by hydrolysis of alpha-tricalcium
      phosphate (alpha-TCP) to CDHAp in pressed precomposite compacts of alpha-TCP-PLGA
      NaCl. The differences in hydrolysis of alpha-TCP-PLGA-NaCl for two compositions
      of 80:10:10 wt % and 60:20:20 wt %. were monitored by isothermal calorimetry and
      X-ray diffraction. The microstructural evolution and variance in final composite
      microstructure after hydrolysis at 37 degrees C, 45 degrees C, and 56 degrees C
      were examined by scanning electron microscopy. HAp-PLGA composite formed from the
      alpha-TCP-PLGA-NaCl (80:10:10) precomposites at 37 degrees C developed a tensile
      strength of 13.3 +/- 0.9 MPa, a flexural strength of 24.8 +/- 1.7 MPa, and
      Young's modulus of 2.8 +/- 0.3 GPa. These values were 12.00 +/- 0.2 MPa, 36.1 +/-
      2.1 MPa, and 5.5 +/- 0.8 GPa for the precomposite composition 60:20:20. All these
      mechanical properties showed a variation with hydrolysis temperature and
      composition. The differences in mechanical properties were related to the final
      microstructures of the composites, which are governed by the morphological
      changes in the polymer structure at its glass transition temperature and the
      extent of cement-type formation of CDHAp by hydrolysis of alpha-TCP.

PMID- 10880123
TI  - Microstructural heterogeneity and the fracture toughness of bone.
AB  - Age-related changes in the skeleton often lead to an increase in the
      susceptibility of bone to fracture. The purpose of this study was to determine
      whether differences in material properties between the osteonal and interstitial
      regions of bone have an effect on bone fracture properties. Parameters such as
      longitudinal fracture toughness, transverse fracture toughness, porosity,
      interstitial microhardness, osteonal microhardness, bone density, and weight
      fractions of the mineral and organic phases of bone were examined as a function
      of age using female baboon femurs. With increasing age, the longitudinal fracture
      toughness decreased significantly as did transverse fracture toughness, whereas
      the interstitial microhardness increased. However, no significant differences in
      the other parameters were observed as a function of age. Using the ratio of
      interstitial microhardness to osteonal microhardness as a measure of the
      differences in the material properties in these two regions, correlation analysis
      revealed that the longitudinal fracture toughness of bone has a significant
      correlation with the microhardness ratio. Localized differences in material
      properties between osteonal and interstitial regions of bone increase with age;
      such differences may result in high stress concentrations at cement lines and
      facilitate longitudinal crack propagation.

PMID- 10880124
TI  - Complement activation on immunoglobulin G-coated hydrophobic surfaces enhances
      the release of oxygen radicals from neutrophils through an actin-dependent
      mechanism.
AB  - Neutrophil granulocytes are among the first cells to encounter a plasma protein
      coated implant and may through frustrated phagocytosis release toxic oxidative
      species. We used two model surfaces, hydrophobic and hydrophilic glass, to
      investigate the effects of plasma immunoglobulin G (IgG)-complement interactions
      for neutrophil adhesion and respiratory burst. The respiratory burst was measured
      with luminol-amplified chemiluminescence and cell adhesion was determined by
      labeling neutrophils with 2', 7'-bis-(carboxy-ethyl)-5(6)-carboxyfluorescein. We
      demonstrate that the IgG-triggered neutrophil adhesion and oxygen radical
      production is augmented in the presence of normal human serum, in particular on
      hydrophobic surfaces, indicating that complement factors enhance the neutrophil
      activation. We propose that the complement factors C3, C5a, and C1q are
      especially important for this amplification, but factor B is probably not.
      Disturbance of the actin filament dynamics with cytochalasin B or jasplakinolide
      blocked the neutrophil radical generation on all surfaces. However, these drugs
      did not affect the number of adherent neutrophils. We suggest that there is a
      synergistic interaction between adsorbed IgG, and the complement system, which
      amplifies the neutrophil acute inflammatory responses through a dynamic actin
      cytoskeleton on synthetic surfaces.

PMID- 10880125
TI  - Collagen type I-coating of Ti6Al4V promotes adhesion of osteoblasts.
AB  - The initial contact of osteoblasts with implant surfaces is an important event
      for osseointegration of implants. Osseointegration of Ti6Al4V may be improved by
      precoating of its surface with collagen type I. In this study, the adhesion of
      rat calvarial osteoblasts to uncoated and collagen type I-coated titanium alloy
      was investigated over a period of 24 h. Collagen type I-coating accelerates
      initial adhesion of osteoblasts in the presence of fetal calf serum. One hour
      after plating, no differences in the percentage of adherent cells between the
      surfaces investigated were found. Adhesion of osteoblasts to uncoated surfaces
      was reduced by the GRGDSP peptide by about 70%, whereas adhesion to collagen type
      I-coated surfaces remained unaffected by treatment of the cells with the peptide.
      Cell adhesion to coated materials was reduced by about 80% by anti-integrin beta1
      antibody. The integrin beta1 antibody did not influence the adhesion to uncoated
      titanium alloy. The results suggest that osteoblasts adhere to collagen type I
      coated materials via integrin beta1 but not by interacting with RGD peptides,
      whereas adhesion to uncoated titanium alloy is mediated by RGD sequences but not
      via integrin beta1. Fibronectin does not seem to be involved in the adhesion of
      osteoblasts to either coated or uncoated titanium alloy.

PMID- 10880126
TI  - Development of biodegradable polyesterurethane membranes with different surface
      morphologies for the culture of osteoblasts.
AB  - To evaluate the biocompatibility of biodegradable polyesterurethane membranes
      with different surface morphologies for their possible use as orthopedic
      biomaterials, rat osteoblasts were cultured on smooth, sunken, and particulate
      polyesterurethane membranes. A close interaction between cells and exposed
      particles on the particulate membranes was found. Cells on the particulate
      surfaces were well spread and flattened and had the greatest adhesion while cells
      on the smooth surfaces were more rounded, less spread, and less adhered. In
      addition, in order to investigate their in vivo degradation rates, the
      morphologic changes in retrieved membranes from 2, 4, and 8 weeks after
      subcutaneous implantation were observed by scanning electron microscopy and their
      average molecular weight changes were determined by gel permeation
      chromatography. These analyses showed that smooth membranes, compared with the
      two other surface membrane types, had the greatest rate and degree of molecular
      weight change. In contrast, the molecular weight of particulate membranes, which
      favor the osteoblast culture, had not changed significantly at 8 weeks
      postimplantation. Thus particulate polyesterurethane membrane surfaces may be of
      use as an orthopedic biomaterial, and polyesterurethane membranes certainly
      provide an ideal system for further study of the relative contributions to
      biocompatibility and degradation derived from surface morphology.

PMID- 10880127
TI  - Song, sexual selection, and a song control nucleus (HVc) in the brains of
      European sedge warblers.
AB  - Female sedge warblers select males that have more complex songs as mates. This
      study tests two predictions concerning HVc, a telencephalic nucleus that is
      essential for song learning and production: first, that males with more complex
      songs will have a larger HVc, and second that males who pair successfully will
      have a larger HVc than unpaired males. Data on song composition and pairing
      status were collected from wild sedge warblers breeding in Hungary. We found
      significant positive correlations between three song attributes (repertoire size,
      song complexity, and song length) and the size of HVc. Males that paired
      successfully also had more complex songs (repertoire size and song complexity,
      though not song length) than males that did not. However, we find no direct
      evidence that males who paired successfully had a larger HVc than unpaired males.
      These findings are discussed in relation to the possible functions of HVc and
      also to current views on sexual selection and the evolution of the song control
      pathway.

PMID- 10880128
TI  - Proteolipid protein mRNA stability is regulated by axonal contact in the rodent
      peripheral nervous system.
AB  - Proteolipid protein (PLP) and its alternatively spliced isoform, DM20, are the
      main intrinsic membrane proteins of compact myelin in the CNS. PLP and DM20 are
      also expressed by Schwann cells, the myelin-forming cells in the PNS, and are
      necessary for normal PNS function in humans. We have investigated the expression
      of PLP in the PNS by examining transgenic mice expressing a LacZ transgene under
      the control of the PLP promoter. In these animals, myelinating Schwann cells
      expressed beta-galactosidase more prominently than nonmyelinating Schwann cells.
      PLP/DM20 mRNA levels, but not those of LacZ mRNA, increased during sciatic nerve
      development and decreased after axotomy, with resultant Wallerian degeneration.
      PLP/DM20 transcription rates, in nuclear run off experiments, however, did not
      increase in developing rat sciatic nerve despite robust increases in PLP/DM20
      mRNA levels during the same period. In RNAse protection studies, PLP mRNA levels
      fell to undetectable levels following nerve transection whereas levels of DM20
      were essentially unchanged despite both being transcribed from the same promoter.
      Finally, cotransfection studies demonstrated that PLP-GFP, but not DM20-GFP mRNA
      is down-regulated in Schwann cells cultured in the absence of forskolin. Taken
      together these data demonstrate that steady state levels of PLP mRNA are
      regulated at a posttranscriptional level in Schwann cells, and that this
      regulation is mediated by Schwann cell-axonal contact. Since the difference
      between these two mRNAs is a 105-bp sequence in PLP and not in DM20, this
      sequence is likely to play a role in the regulation of PLP mRNA.

PMID- 10880129
TI  - Different extrinsic trophic factors regulate neurite outgrowth and synapse
      formation between identified Lymnaea neurons.
AB  - The requirement for trophic factors in neurite outgrowth is well established,
      though their role in synapse formation is yet to be determined. Moreover, the
      issue of whether the trophic factors mediating neurite outgrowth are also
      responsible for synapse specification has not yet been resolved. To test whether
      trophic factors mediating neurite outgrowth and synapse formation between
      identified neurons are conserved in two molluscan species and whether these
      developmental processes are differentially regulated by different trophic
      factors, we used soma-soma and neurite-neurite synapses between identified
      Lymnaea neurons. We demonstrate here that the trophic factors present in Aplysia
      hemolymph, although sufficient to induce neurite outgrowth from Lymnaea neurons,
      do not promote specific synapse formation between excitatory partners.
      Specifically, the identified presynaptic neuron visceral dorsal 4 (VD4) and
      postsynaptic neuron left pedal dorsal 1 (LPeD1) were either paired in a soma-soma
      configuration or plated individually to allow neuritic contacts. Cells were
      cultured in either Lymnaea brain-conditioned medium (CM) or on poly-L-lysine
      dishes that were pretreated with Aplysia hemolymph (ApHM), but contained only
      Lymnaea defined medium (DM; does not promote neurite outgrowth). In ApHM-coated
      dishes containing DM, Lymnaea neurons exhibited extensive neurite outgrowth, but
      appropriate excitatory synapses failed to develop between the cells. Instead,
      inappropriate reciprocal inhibitory synapses formed between VD4 and LPeD1.
      Similar inappropriate inhibitory synapses were observed in Aplysia hemolymph
      pretreated dishes that contained dialyzed Aplysia hemolymph. These inhibitory
      synapses were novel and inappropriate, because they do not exist in vivo. A
      receptor tyrosine kinase inhibitor (Lavendustin A) blocked neurite outgrowth
      induced by both Lymnaea CM and ApHM. However, it did not affect inappropriate
      inhibitory synapse formation between the neurons. These data demonstrate that
      neurite outgrowth but not inappropriate inhibitory synapse formation involves
      receptor tyrosine kinases. Together, our data provide direct evidence that
      trophic factors required for neurite outgrowth are conserved among two different
      molluscan species, and that neurite extension and synapse specification between
      excitatory partners are likely mediated by different trophic factors.

PMID- 10880130
TI  - The actions of crustacean cardioactive peptide on adult and developing
      stomatogastric ganglion motor patterns.
AB  - The motor patterns produced by the stomatogastric ganglion (STG) are strongly
      influenced by descending modulatory inputs from anterior ganglia. With these
      inputs intact, in control saline, the motor patterns produced by the
      stomatogastric nervous system of embryonic and larval lobsters are slower and
      less regular than those of adult lobsters. We studied the effects of the hormonal
      modulator, crustacean cardioactive peptide (CCAP) on the discharge patterns of
      STG motor patterns in embryos, larvae, and adult Maine lobsters, Homarus
      americanus, with the anterior inputs present and absent. In adults, CCAP
      initiated robust pyloric rhythms from STGs isolated from their descending control
      and modulatory inputs. Likewise, CCAP initiated robust activity in isolated
      embryonic and larval STGs. Nonetheless, quantitative analyses revealed that the
      frequency and regularity of the STG motor neuron discharge seen in the presence
      of CCAP in isolated STGs from embryos were significantly lower than those seen
      late in larval life and in adults under the same conditions. In contrast, when
      the descending control and modulatory pathways to the STG were left intact, the
      embryonic and larval burst frequency seen in the presence of CCAP was increased
      by CCAP, whereas the burst frequency in adults was decreased by CCAP, so that in
      CCAP the frequencies at all stages were statistically indistinguishable. These
      data argue that immature embryonic motor patterns seen in the absence of CCAP are
      a function of immaturity in both the STG and in the descending and modulatory
      pathways.

PMID- 10880131
TI  - Spike-dependent calcium influx in dendrites of the cricket giant interneuron.
AB  - Identified wind-sensitive giant interneurons in the cricket's cercal sensory
      system integrate cercal afferent signals and release an avoidance behavior. A
      calcium-imaging technique was applied to the giant interneurons to examine the
      presence of the voltage-dependent Ca(2+) channels (VDCCs) in their dendrites. We
      found that presynaptic stimuli to the cercal sensory nerve cords elevated the
      cytosolic Ca(2+) concentration ([Ca(2+)](i)) in the dendrites of the giant
      interneurons. The dendritic Ca(2+) rise coincided with the spike burst of the
      giant interneurons, and the rate of Ca(2+) rise depended on the frequency of the
      action potentials. These results suggest that the action potentials directly
      caused [Ca(2+)](i) increase. Observation of the [Ca(2+)](i) elevation induced by
      depolarizing current injection demonstrates the presence of the VDCCs in the
      dendrites. Although hyperpolarizing current injection into the giant interneuron
      suppressed action potential generation, EPSPs could induce no [Ca(2+)](i)
      increase. This result means that ligand-gated channels do not contribute to the
      synaptically stimulated Ca(2+) elevation. On the other hand, antidromically
      stimulated spikes also increased [Ca(2+)](i) in all cellular regions including
      the dendrites. And bath application of a mixture of Ni(2+), Co(2+), and Cd(2+) or
      tetrodotoxin inhibited the [Ca(2+)](i) elevation induced by the antidromic
      stimulation. From these findings, we suppose that the axonal spikes
      antidromically propagate and induce the Ca(2+) influx via VDCCs in the dendrites.
      The spike-dependent Ca(2+) elevation may regulate the sensory signals processing
      via second-messenger cascades in the giant interneurons.

PMID- 10880132
TI  - Binding sites of Drosophila melanogaster sex peptide pheromones.
AB  - Drosophila melanogaster sex peptide (SP) and Ductus ejaculatorius peptide
      (DUP99B) are male pheromones transferred in the seminal fluid to the female
      during copulation. Both reduce sexual receptivity and stimulate oviposition in
      females. The presence of high-affinity SP and DUP99B binding sites in the female
      were investigated by incubation of cryostat tissue sections with (125)I-iodinated
      peptides and subsequent autoradiography. We found that in adult females
      radiolabeled SP and DUP99B bind to peripheral nerves, the subesophageal ganglion,
      the cervical connective, to discrete parts of the thoracic ganglion, and to the
      genital tract. Weak and uniform labeling was detected in the neuropil of the
      brain and the thoracic ganglion. The labeling pattern in the nervous system
      suggests binding of the peptides to sensory afferents or glial cells. Scatchard
      analysis of the binding of (125)I-DUP99B to antennal nerves yielded a
      dissociation constant K(d) of 6.4 nM. Competition experiments with peptide
      fragments show that the peptides bind with their homologous C-terminal regions.
      Binding sites in the nervous system of females are established throughout sexual
      maturation. Prominent binding of the peptides to afferent nerves suggests
      modification of sensory input.

PMID- 10880133
TI  - Synthesis and functional integration of a neurotransmitter receptor in isolated
      invertebrate axons.
AB  - Neurotransmitter receptors are considered an important class of membrane proteins
      that are involved in plasticity-induced changes underlying learning and memory.
      Recent studies, which demonstrated that the mRNAs encoding for various receptor
      proteins are localized to specific dendritic domains, allude toward the
      possibility that these membrane bound molecules may be synthesized locally.
      However, direct evidence for the local axonal or dendritic synthesis and
      functional integration of receptor proteins in either vertebrates or
      invertebrates is still lacking. In this study, using an invertebrate model system
      we provide the first direct evidence that isolated axons (in the absence of the
      soma) can intrinsically synthesize and functionally integrate a membrane-bound
      receptor protein from an axonally injected mRNA. Surgically isolated axons from
      identified neurons were injected with mRNA encoding a G-protein-coupled
      conopressin receptor. Immunocytochemical and electrophysiological techniques were
      used to demonstrate functional integration of the receptor protein into the
      membrane of the isolated axon. Ultrastructural analysis of axonal compartments
      revealed polyribosomes, suggesting that some components of the protein
      synthesizing machinery are indeed present in these extrasomal compartments. Such
      axonal propensity to locally synthesize and functionally insert transmitter
      receptors may be instrumental in plasticity induced changes, for instance those
      that underlie learning and memory.

PMID- 10880134
TI  - Early sensory and hormonal experience modulate age-related changes in NR2B mRNA
      within a forebrain region controlling avian vocal learning.
AB  - Male zebra finches are most apt to mimic songs heard between posthatch days (PHD)
      35 and 65, and this vocal learning depends, in part, on the activation of N
      methyl-D-aspartate receptors (NMDAR) within a discrete forebrain circuit that
      includes the lateral magnocellular nucleus of the anterior neostriatum (lMAN) and
      area X. Using in situ hybridization, we show that transcripts for both the
      constitutive NMDAR subunit NR1 and the modulatory subunit NR2B decrease abruptly
      in the lMAN between PHD20 and 40. This downregulation corresponds to the onset of
      song learning and a transition from slow to faster NMDAR currents in lMAN
      neurons. In area X, NR1 mRNA increases as NR2B mRNA decreases during song
      development. To understand how these changes in NMDAR mRNA might regulate song
      learning, we next investigated how manipulations that influence song development
      affect NMDAR mRNA expression. Early isolation from conspecific song (which delays
      closure of the sensitive period for song learning) selectively increases NR2B,
      but not NR1 mRNA, within lMAN at PHD60. In contrast, exposure to testosterone
      beginning at PHD20 (which impairs song development and hastens the developmental
      transition to faster NMDAR current kinetics within lMAN) accelerates the decline
      in NR2B mRNA in lMAN, again without affecting NR1 transcript levels. Neither
      manipulation significantly effects NR1 or NR2B mRNA levels in area X. Our data
      suggest that developmental changes in the expression of specific NMDAR subunits
      may regulate periods of neural and behavioral plasticity and that flexibility in
      the timing of these sensitive periods may be achieved through experience and/or
      hormone-dependent modulation of NMDAR gene expression.

PMID- 10880135
TI  - Refractory ceramic fiber: toxicology, epidemiology, and risk analyses--a review.
AB  - Refractory ceramic fiber (RCF) is an energy-efficient, high-temperature
      insulation, used principally in industrial furnaces, heaters, and reactors. Prior
      to the 1980s, there were few publications dealing with the potential health
      effects of this material. However, with the advent of higher energy costs and the
      need for thermally efficient high-temperature insulating materials, production of
      RCF grew rapidly, as did interest in its potential health effects. This article
      provides a comprehensive and integrated review of the toxicology (in vitro and in
      vivo), epidemiology, and risk analysis literature of RCF. Based on the available
      literature, we conclude that an occupational exposure of 0.5 fibers per cubic
      centimeter (cm(3)) [8-h time-weighted average (8-h TWA)] results in an
      occupational health risk no greater than 9.1 x 10(-5).

PMID- 10880136
TI  - Soluble components of Utah Valley particulate pollution alter alveolar macrophage
      function in vivo and in vitro.
AB  - Water-soluble extracts of Utah Valley dust (UVD) have been found to cause
      inflammatory injury of the lung in both humans and rodents. The degree of lung
      damage found correlated with the metal content in the extracts. In the present
      study, extracts of a set of UVD PM(10) filters collected over a 3-yr span,
      varying in total metal content with yr 1 = yr 3 > yr 2, were used to assess
      effects on human alveolar macrophage (AM) function. The phagocytic activity and
      oxidative response of AM was investigated 24 h after segmental instillation of
      UVD, or after overnight in vitro culture of the extracts with AM. Using flow
      cytometry analysis, AM phagocytosis of fluorescently (FITC)-labeled Saccharomyces
      cerevisiae was inhibited following instillation of UVD1 (61%) but not by yr 2 and
      3. Neither baseline oxidant activity nor phorbol ester-induced oxidant generation
      was affected by the dust extracts in vivo. Overnight culture of AM with UVD1
      resulted in a significant decrease in the percentage of AM phagocytizing
      particles (30%), while no significant effect on this function was found with the
      other two extracts. Furthermore, only UVD1 caused an immediate oxidative response
      in AM, although both UVD1 and UVD3 inhibited oxidant activity in AM when the
      cells were incubated with the extracts overnight. The detrimental effects on AM
      host defenses could be due to apoptosis, which was evident in cells exposed to
      the UVD1 and to a much lesser extent with AM exposed to yr 2 and 3. The
      component(s) responsible for the toxic effects on AM in vitro were removed by
      pretreatment of the UVD extracts with a polycation chelating resin, chelex-100.
      However, since yr 1 and 3 are similar in their soluble metal content, but differ
      in their effects on AM phagocytosis, it is possible that the metals may not be
      the culprit in effects of particulate matter on AM host defense.

PMID- 10880137
TI  - Inhalation toxicity of potassium octatitanate fibers (TISMO) in rats following 13
      weeks of aerosol exposure.
AB  - One hundred and forty male and 140 female rats were divided into 1 control and 3
      test groups of 35 rats each, per sex, and exposed by whole-body inhalation to
      test compound at target concentrations of 0, 1 mg/m(3) (1700 fibers/cm(3), 123
      WHO fibers/cm(3)), 10 mg/m(3) (5900 fibers/cm(3), 952 WHO fibers/cm(3)), and 100
      mg/m(3) (112,700 fibers/cm(3), 7440 WHO fibers/cm(3)) for 6 h/day, 5 days/wk for
      13 wk. Ten rats from each group were killed after 13 wk of exposure and 13 wk of
      recovery, respectively, for histopathological evaluation. The other 15 rats from
      each group were killed to study lung clearance after 91 days of exposure, and
      approximately 1.5 and 3 mo of recovery following the end of the 13 wk of
      exposure. The mean fiber length of the chamber atmosphere was 2.8, 2.7, and 2.8
      microm, while the mean fiber width was 0.48, 0.48, and 0.45 microm for the 1-, 10
      , and 100-mg/m(3) chambers, respectively. In the 1-mg/m(3) (123 WHO fibers/cm(3))
      exposure group, inhaled particles were mostly retained in a few fiber-laden
      alveolar macrophages (AMs) within the alveoli adjacent to alveolar ducts without
      any adverse tissue response throughout 13 wk of exposure and following 13 wk of
      recovery. This exposure concentration was considered to be a no-observable
      adverse-effect level (NOAEL), since the alveoli containing fiber-laden AMs
      preserved normal structure. After 13 wk of exposure to 10 mg/m(3) (952 WHO
      fibers/cm(3)), fiber-laden AMs were mainly retained at the alveoli adjacent to
      the alveolar ducts. Infrequently, slight fibrotic thickening was observed in the
      alveolar ducts and adjoining alveoli, with proliferating fibroblasts and
      hyperplastic Type II pneumocytes, and microgranulomas. Occasionally, trace
      amounts of collagenous material were deposited in the thickened alveolar ducts
      and adjoining alveolar walls. In addition, minimal alveolar bronchiolarization
      was occasionally found in the alveoli adjacent to the terminal bronchioles. The
      peribronchial lymphoid tissue and thymic lymph nodes contained migrated fiber
      laden AMs. After 13 wk of recovery, fiber-laden AMs had mostly disappeared from
      alveoli located in the peripheral acini, but they localized in the alveolar ducts
      region, suggesting there was active lung clearance of fibers by the AMs via
      airways. Thickened alveolar ducts and adjacent alveoli were decreased in
      thickness, a reversible change manifested by reduction of proliferating Type II
      pneumocytes and fibroblasts. Collagenized fibrosis was slightly more pronounced
      in the thickened alveolar ducts and adjoining alveoli. The lung response
      following 13 wk of exposure to 100 mg/m(3) (7440 WHO fibers/cm(3)) and after 13
      wk of recovery was similar to those findings of the 952 WHO fibers/cm(3) group
      but more pronounced, demonstrating a clear concentration-related response.
      Alveolar ducts and adjoining alveolar walls in the central acini were irregularly
      thickened with more frequent evidence of minimal collagenized fibrosis. The lung
      burden and clearance of fibers were estimated by measuring the total content of
      titanium (Ti) in the lungs, but high variability of Ti content in control and
      exposed groups prevented meaningful lung clearance analysis.

PMID- 10880138
TI  - Comparative metabolism of low concentrations of butadiene and its monoepoxide in
      human and monkey hepatic microsomes.
AB  - The chronic (2-yr) inhalation toxicity of 1,3-butadiene (BD), a chemical used in
      large quantities to make rubber and plastics, differs greatly between mice and
      rats. Mice develop lung tumors after exposures to concentrations as low as 6.25
      ppm, whereas rats develop mammary tumors only after exposures to 1000-8000 ppm
      BD. Extensive research has been carried out to determine where humans fit into
      this susceptibility range. Species differences in rates of metabolism of BD have
      been noted, but inconsistencies in metabolism data from different laboratories
      and some problems in the fit of physiologically based pharmacokinetic (PBPK)
      models with experimental data have left uncertainties. The experiments reported
      here are intended to clarify the issue of human metabolism of BD and to determine
      if metabolism of BD in cynomolgus monkeys is similar enough to metabolism in
      humans to use in vivo data from monkeys for PBPK modeling. The results indicate
      that for the reactions studied (oxidation of BD to the mono- and diepoxide), BD
      is metabolized substantially the same in monkey and human hepatic microsomes. The
      human metabolism data agreed with that reported earlier when the in vitro
      metabolism of BD was studied at low BD concentrations. Finally, BD at high
      concentrations was found to inhibit the further oxidation of its metabolite, the
      monoepoxide. Incorporation of this information on the competition between BD and
      its first oxidation product for CYP2E1 should improve the fit of PBPK models.

PMID- 10880139
TI  - In vivo and in vitro correlation of pulmonary MAP kinase activation following
      metallic exposure.
AB  - Residual oil fly ash (ROFA) is a particulate pollutant produced in the combustion
      of fuel oil. Exposure to ROFA is associated with adverse respiratory effects in
      humans, induces lung inflammation in animals, and induces inflammatory mediator
      expression in cultured human airway epithelial cells (HAEC). ROFA has a high
      content of transition metals, including vanadium, a potent tyrosine phosphatase
      inhibitor that we have previously shown to disregulate phosphotyrosine metabolism
      and activate mitogen-activated protein kinase (MAPK) signaling cascades in HAEC.
      In order to study MAPK activation in response to in vivo metal exposure, we used
      immunohistochemical methods to detect levels of phosphorylated protein tyrosines
      (P-Tyr) and the MAPKs ERK1/2, JNK, and P38 in lung sections from rats
      intratracheally exposed to ROFA. After a 1-h exposure to 500 microg ROFA, rat
      lungs showed no histological changes and no significant increases in
      immunostaining for either P-Tyr or phospho-(P-) MAPKs compared to saline
      instilled controls. At 4 h of exposure, there was mild and variable inflammation
      in the lung, which was accompanied by an increase in specific immunostaining for
      P-Tyr and P-MAPKs in airway and alveolar epithelial cells and resident
      macrophages. By 24 h of exposure, there was a pronounced inflammatory response to
      ROFA instillation and a marked increase in levels of P-Tyr and P-MAPKs present
      within the alveolar epithelium and in the inflammatory cells, while the airway
      epithelium showed a continued increase in the expression of P-ERK1/2. By
      comparison, HAEC cultures exposed to 100 microg/ml ROFA for 20 min resulted in
      marked increases in P-Tyr and P-MAPKs, which persisted after 24 h of exposure. P
      Tyr levels continued to accumulate for up to 24 h in HAEC exposed to ROFA. These
      results demonstrate in vivo activation in cell signaling pathways in response to
      pulmonary exposure to particulate matter, and support the relevance of in vitro
      studies in the identification of mechanisms of lung injury induced by pollutant
      inhalation.

PMID- 10880140
TI  - Morphological changes in rat lung after long-term exposure to diesel emissions.
AB  - Wistar rats were exposed for 24 mo to diesel emissions containing a low (0.2 ppm,
      0.21 mg/m(3)), medium (1.04 ppm, 1.18 mg/m(3)), or high (2.96 ppm, 3.05 mg/m(3))
      concentration of NO(2) and particles, or diesel emissions containing a medium
      (1.12 ppm, 0.01 mg/m(3)) concentration of NO(2) without particles. At 6-mo
      intervals during the exposure period, rats were autopsied, and their lungs were
      prepared for light- and electron-microscopic examination. Morphological
      evaluations included examination for hyperplasia of airway goblet cells, shift in
      the types of glycoprotein of intracellular mucus granules in goblet cells,
      infiltration of inflammatory cells in the airways, enlargement of the cross
      sectional area of an alveolus as a parameter of air space enlargement, and
      development of alveolar holes, which is considered to be an early hallmark of
      alveolar destruction. The number of goblet cells with acid-form mucus granules
      increased with the exposure concentration and time; however, goblet cells did not
      show any hyperplastic changes. Furthermore, inflammatory cells such as alveolar
      macrophages, mast cells, plasma cells, neutrophils, and lymphocytes infiltrated
      the airways and the alveoli, and showed some cell-to-cell contact. Although no
      significant enlargement of the air space of the lungs was seen in any exposure
      group, the number of alveolar holes was significantly higher in the high
      concentration group in comparison with the control group at each exposure time,
      and also increased in other exposure groups, even in the low-concentration group
      at certain exposure times. Morphological changes in the lungs were mild even in
      the animals exposed to the highest levels of diesel emissions for 24 mo.
      Elimination of particles from diesel emissions led to reduced morphological
      changes such as a decreased shift in the types of glycoprotein of mucus granules
      in goblet cells, decreased infiltration of inflammatory cells in the lungs, and
      reduced anthracosis.

PMID- 10880141
TI  - A lung model describing uptake of organic solvents and roles of mucosal blood
      flow and metabolism in the bronchioles.
AB  - A simple lung model (mucosal blood flow and metabolism model, MBM model) was
      developed to describe the uptake of organic solvents and investigate the role of
      mucosal blood flow and metabolism. The model separates the lung into four
      compartments, the peripheral bronchial tract (gas phase), the mucus layer lining
      the wall surface of the tract, the alveolar space (gas phase), and the alveolar
      blood. Solvent molecules are absorbed in the mucus layer during inhalation and
      released during exhalation. The deposited solvent diffuses radially into the
      mucosal tissue of the respiratory tract and transfers to the mucosal blood flow.
      To describe this behavior, a hypothetical mucosal blood flow throughout the mucus
      layer was used. The solvent in the mucosal tissue may be also metabolized, and a
      hypothetical metabolism in the mucus layer was used. The rate of the hypothetical
      mucosal blood flow was determined to be 5.2 ml/min based on the best fitting of
      previously obtained data for seven polar organic solvents. The MBM model predicts
      that as the blood-air partition coefficient (lambda(B)) increases from 0.1 to 20,
      the relative end-exhalation (E(end)) will decrease from 0.89 to 0.07, and as
      lambda(B) increases to 500, E(end) will increase to 0.33. After lambda(B) = 500,
      E(end) is predicted to decrease again, and at lambda(B) = 10000, E(end) is 0.09.
      The model also predicts that as lambda(B) increases from 0.1 to 10, the relative
      uptake (U) increases from 0.08 to 0.61, and as lambda(B) increases to 150, U
      decreases to 0.50. After lambda(B) = 150, U increases again, and at lambda(B) =
      10,000, U is 0.8. The predictions show good agreement with values observed in
      human experimental studies. The MBM model predicts that uptake by the mucosal
      blood (U(Al)) would be equal to uptake by the alveolar blood (U(Mu)) at lambda(B)
      of 1000 and U(Al) is more than 90% of total uptake at lambda(B) > 10,000. The
      model also shows that U is significantly increased by the mucosal metabolism at
      lambda(B) between 50 and 5000. Especially, U in the case of CL(Mu) = 100 ml/min
      is higher by 0.3 than that in the nonmucosal metabolism.

PMID- 10880142
TI  - Modulation in the developmental expression profile of Sp1 subsequent to
      transplacental exposure of fetal rats to desorbed benzo[a]pyrene following
      maternal inhalation.
AB  - Any alteration of the critical sequence of genes that are required to coordinate
      the differentiation of cells, the promotion of migration, dendritic arborization,
      synapse formation, and myelination in the developing nervous system would be
      expected to have deleterious consequences. The focus of this article is a
      molecular evaluation of the neurotoxicological effects that result subsequent to
      the transplacental exposure of fetal rats to desorbed benzo(a)pyrene (BaP)
      following maternal inhalation. A state-of-the-art, newly designed, fabricated,
      and tested model aerosol generation system was utilized in these studies. Timed
      pregnant Sprague Dawley rats were exposed for 4 h on gestation day 15 of a 21-day
      gestation period to an acute dose of BaP:carbon black aerosol (100 microg/m(3)).
      Controls received carbon black only. Nominal and chamber concentrations of the
      particulate aerosol were determined gravimetrically with a seven-stage cascade
      impactor. The aerosol exhibited a trimodal distribution with 95% cumulative mass
      less than 15.85 microm, 90% cumulative mass less than 10 microm, 67. 5%
      cumulative mass less than 2.5 microm and 66.2% cumulative mass less than 1.0
      microm. Time-course bioavailability results indicated that greater than 95% of
      the parent compound is cleared from blood 240 min postexposure. An Sp1
      transcription factor consensus sequence was examined by electrophoretic mobility
      shift analysis of nuclear extracts from various brain regions of resulting pups
      on postnatal days 3, 5, 7, 10, and 15. It revealed perturbations in the
      developmental expression profile of Sp1 abundance as a result of nose-only
      particulate aerosol exposure to the timed-pregnant dam. The data obtained on the
      temporal and spatial regulation of gene expression in the brain indicate that (1)
      Sp1 DNA-binding is developmentally regulated and expressed very highly in
      actively developing brain regions, and (2) a consequence of the transplacental
      deposition of desorbed BaP to the fetus is in utero neurotoxicity.

PMID- 10880143
TI  - Exposure to air pollution is associated with lung hyperinflation in healthy
      children and adolescents in Southwest Mexico City: a pilot study.
AB  - Air pollution produces adverse health effects. The consequences of lifelong daily
      exposures to atmospheric pollutants upon the respiratory apparatus of healthy
      children are of considerable clinical importance. We investigated the association
      between exposure to a highly polluted urban environment with a complex mixture of
      air pollutants-ozone and particulate matter the predominant ones-and chest x-ray
      abnormalities in 59 healthy Mexican children who are lifelong residents of
      Southwest Metropolitan Mexico City (SWMMC), with a negative history of tobacco
      exposure and respiratory illnesses. Their clinical results and x-ray findings
      were compared to those of 19 Mexican control children, residents of a low
      pollution area, with a similar negative history of tobacco exposure and
      respiratory illnesses. Ozone concentrations in SWMMC exceeded the U.S.
      Environmental Protection Agency (U.S. EPA) National Ambient Air Quality Standard
      (NAAQS) for O(3): 0.08 ppm as 1-h maximal concentration, not to be exceeded more
      than 4 times a year, on 71% of days in 1986 and 95% in 1997, with values as high
      as 0.48 ppm. Ozone maximal peaks are usually recorded between 2 and 5 pm
      coinciding with children's outdoor physical activities. Children in the control
      group reported no upper or lower respiratory symptomatology. Every SWMMC child
      complained of upper and/or lower respiratory symptoms, including epistaxis, nasal
      dryness and crusting, cough, shortness of breath, and chest discomfort. Children
      aged 7-13 yr had the most symptomatology, while 5- to 6-year olds and adolescents
      with the lowest number of statistically significant outdoor exposure hours had
      less respiratory symptoms. Bilateral symmetric mild lung hyperinflation was
      significantly associated with exposure to the SWMMC atmosphere (p = .0004).
      Chronic and sustained inhalation of a complex mixture of air pollutants,
      including ozone and particulate matter (PM), is associated with lung
      hyperinflation, suggestive of small airway disease, in a population of clinically
      healthy children and adolescents. Small airways are a target of air pollutants in
      SWMMC children, with ozone and PM being most likely responsible, based on
      experimental animal, controlled-chamber, and epidemiological data available. Our
      main concern is the potential likelihood for the development of chronic lung
      disease in this highly exposed population.

PMID- 10880144
TI  - An exposure system to study the effects of water-soluble gases on PM-induced
      toxicity.
AB  - An aerosol generation and exposure system to evaluate the role of water-soluble
      gases in particulate matter (PM)-induced injury was designed, built, and
      validated by generating test atmospheres to study the role of hydrogen peroxide
      in PM-induced toxicity. In this system, particle number concentration, size
      distribution, hydrogen peroxide concentration, and water concentration can all be
      varied. An ammonium sulfate aerosol with mass median diameter 0.46 +/- 0.01
      microm was used as a model atmospheric aerosol because ammonium sulfate is a
      major component of the fine aerosol, and the water uptake of ammonium sulfate
      aerosol is well characterized. The following four test atmospheres were
      generated: (1) ammonium sulfate aerosol, (2) an aerosol containing hydrogen
      peroxide and ammonium sulfate, (3) vapor-phase hydrogen peroxide, and (4)
      particle-free air. All test atmospheres were maintained at a relative humidity of
      85%. Particle size distribution, number concentration, total hydrogen peroxide
      concentration, temperature, and relative humidity were measured continuously in
      the exposure chamber. The gas-particle partitioning of hydrogen peroxide was
      calculated using total hydrogen peroxide concentration, the Henry's law constant
      for hydrogen peroxide in water, and aerosol water content. We found that the
      aerosol generation system produced stable concentrations throughout the 2-hour
      exposures.

PMID- 10880145
TI  - Ozone adaptation in mice and its association with ascorbic acid in the lung.
AB  - We have previously shown that ozone (O(3)) adaptation occurred in rats after
      daily exposure to an "urban-type" concentration. The adaptation was positively
      associated with an excess of ascorbic acid (AA) in bronchoalveolar lavage fluid
      (BALF), suggesting that AA may play a role in the adaptation mechanism. This
      relationship was not seen at higher and more toxic exposures. The present work
      exposed mice to low and high levels of O(3) to see if the adaptation-AA
      relationship is common among rodent species. Male CD-1 mice were studied during
      repeated 6-h/day exposures to 0.0 or 0.25 ppm O(3) for 10 days and 10 days of
      recovery in air (experiment 1) and to 0.0, 0.5, or 1.0 ppm O(3) for 5 days
      (experiment 2). Approximately 20 h after each daily exposure, groups of mice were
      randomly selected from each concentration type and examined for patterns of
      response. They were anesthetized (urethane, ip), intubated, and the lungs were
      lavaged with 37 degrees C saline. BALF was assayed for cells, cell differential,
      protein, albumin, lactate dehydrogenase, lysozymes, N-acetyl-beta-D
      glucosaminidase, gamma-glutamyl transferase, uric acid, glutathione, and AA. Body
      weight and total lung capacity were also measured. Mice from experiment 1
      (10/exposure) were tested for adaptation on day 12 by challenging them with 1.0
      ppm O(3) for 6 h and collecting BALF 20 h later. In experiment 2, adaptation was
      assessed by evaluating the attenuation in response to continued exposure. There
      was only minimal response to the daily O(3) exposures in experiment 1 except for
      AA, which was significantly increased in BALF by day 3 and remained elevated well
      into the recovery period. The O(3)-preexposed mice demonstrated adaptation when
      compared to their O(3)-naive counterparts. Daily exposure to 1. 0 ppm O(3) in
      experiment 2 caused weight loss and changes in BALF consistent with toxicity, and
      neither adaptation nor an excess quantity of AA was seen. The findings in mice
      were in agreement with those seen in rats and suggest that there may be a common
      O(3) adaptation mechanism among rodents that involves the regulation of AA in
      lung lining fluid.

PMID- 10880146
TI  - Repeated pulmonary function measurements in rats after intratracheal instillation
      of a polyamine textile pigment component.
AB  - The pulmonary response of Wistar rats to a cumulative dose of 1 mg/kg body weight
      of a polymeric alpha,omega-diamine was examined using the intratracheal route of
      administration. Instillation of the test substance was on days 0 and 7 followed
      by a 3-month postobservation period. Static and dynamic pulmonary function tests,
      including arterial blood gas determinations, were performed during wk 5, 9, and
      13. At all time points, significantly depressed flow-volume curves, reduced
      quasistatic compliance, and reduced vital capacity were observed. These were
      associated with increases of residual volume and functional residual capacity in
      the presence of unremarkable changes of total lung capacity (TLC). One of the
      most predominant dysfunctions of the lung was a severe maldistribution of
      ventilation, indicated by the single-breath nitrogen washout test. The carbon
      monoxide diffusing capacity (DL(CO)), in turn, was only mildly decreased, and
      differences between treatment and control groups did not reach statistical
      significance. Assessment of arterial blood gases demonstrated a statistically
      significantly increased venous admixture with subsequent slight hypoxemia. In
      summary, the predominant dysfunction appeared to be consistent with an
      obstructive rather than restrictive lung disease. The functional changes observed
      may account for the effect on arterial blood gases, suggesting a mismatch of the
      ventilation-perfusion relationship. Either measurement appear to demonstrate a
      relative stable dysfunction during the 3-mo postinstillation observation period.
      Collectively, this study supports the view held that polymeric alpha, omega
      diamines appear to be potent pneumotoxicants.

PMID- 10880147
TI  - A comparative respiratory sensitization study of 2,4- and 2,6-toluene
      diisocyanate using guinea pigs.
AB  - The potential exposure of workers to both 2,4-toluene diisocyanate (2,4-TDI) and
      2,6-TDI led to an investigation of the comparative respiratory sensitization
      potential of these two isomers. Separate groups of guinea pigs were either sham
      exposed or exposed to one of the isomers 3 h/day for 5 consecutive days
      (sensitization phase). The mean concentration during the sensitization phase
      ranged from 1. 29 to 1.40 ppm. The animals were then conventionally housed for 2
      wk and challenged for 1 h on 3 subsequent weeks with either the same isomer or
      the alternate isomer. The first 2 wk of the challenge phase involved exposure to
      TDI vapor (18 to 46 ppb), whereas the third challenge was to an aerosol of TDI
      guinea pig serum albumin (GPSA) conjugate (18 to 32 mg/m(3)). The endpoint used
      to detect both immediate-onset and delayed-onset hypersensitivity responses was
      respiratory rate. Body weights and clinical signs were also recorded. There were
      clear decrements in weight gain in response to the wk 1 exposure to either isomer
      of TDI, but no isomer-specific differences were observed. Clinical signs revealed
      irritation to the respiratory tract only during the sensitization phase. A single
      animal challenged with TDI-GPSA may have experienced a severe anaphylactic
      response during the challenge phase. The incidence of immediate-onset
      hypersensitivity responses resulting from challenge with TDI vapor was less
      robust and less consistent than that resulting from challenge with the TDI-GPSA
      conjugate. All groups sensitized with either isomer showed an increased incidence
      of responders. There was no apparent difference between the two isomers. The
      delayed-onset phase produced more spontaneous variability in spontaneous
      respiratory rates and was not amenable to analysis for response to TDI challenge.
      Thus, no isomer-dependent differences were observed.

PMID- 10880148
TI  - Analysis of potential transfer of continuous glass filament from Eclipse
      cigarettes.
AB  - This study was designed to determine if a prototype of the Eclipse cigarettes,
      which uses a special form of continuous glass filament (CGF) as an insulator
      around the carbon heat source, yielded CGFs via mainstream smoke. A method was
      developed that used electrostatic precipitation with a greater than 99%
      collection efficiency of mass to capture CGFs transferred to mainstream smoke.
      The cigarettes were smoked using an exaggerated puffing condition that was more
      than twice the Federal Trade Commission (FTC) standard. The cigarettes were
      subjected to handling procedures that simulated commercial shipping conditions
      prior to smoking. CGFs were intentionally added to a series of smoke condensate
      samples to determine CGF recovery efficiency. The recovery efficiency was
      determined for a series of four internal standards added to smoke condensate. The
      recovery efficiency was 86% for the Eclipse 5-014 prototype. The number of CGFs
      in smoke condensate collected from the Eclipse 5-014 prototype was approximately
      0.06 +/- 0.02 CGFs per cigarette (+/- standard deviation), including the
      background counts of CGFs and 0.03 CGFs per cigarette, when corrected for
      background contributions. The number of CGFs found in smoke condensates for this
      prototype was not statistically distinguishable from zero or background in these
      experiments, which were capable of detecting transfer rates of greater than 0.2
      CGFs per cigarette.

PMID- 10880149
TI  - Acute effects of smoking of cigarettes with different tar content on plasma
      oxidant/antioxidant status.
AB  - In this study, acute effects of two different types of cigarette smoking on
      plasma oxidant/antioxidant status were investigated. For this purpose,
      malondialdehyde (MDA) levels and antioxidant potential (AOP) values were measured
      in the plasma samples before and after cigarette smoking at fasting. After the
      first blood sample was obtained, second and third samples were withdrawn at 1.5 h
      and 3 h. In the first group, subjects smoked five cigarettes with full flavor
      (FF), and in the second group, five cigarettes with full-flavor low tar (FFLT).
      Quality classification is made mainly on the basis of tar content of the
      products. The cigarette with 23 mg tar is defined as FF and that with 12 mg tar
      as FFLT. MDA level was found to be significantly increased in the 1.5-h plasma
      samples of both groups, but the increase was greater in the FF group. AOP values,
      however, were found to be lower in the 3-h plasma samples of both groups, but the
      decrease was greater in the FF group compared with the FFLT group. It appears
      that acute smoking causes oxidant stress in blood plasma once exposed to smoke,
      and then this effect (MDA) begins to decrease. On the other hand, AOP is lowered
      due to oxidant stress created by smoke. With regard to the types of cigarettes,
      the FF product seems to be more oxidant than the FFLT product. Our results
      suggest that antioxidant supplementation might be beneficial for the smokers to
      cope with the oxidant load derived from cigarette smoke. It is also clearly seen
      from these results that cigarette manufacturers should reduce tar/nicotine ratio
      in their products in order to lessen the toxic effects of smoking without causing
      increased need to smoke.

PMID- 10880150
TI  - Characterization of respiratory exposure to and effects of cold-air
      hyperventilation in guinea pigs.
AB  - The purpose of this study was to characterize the respiratory effects of single
      and repeated controlled exposures to clean warm humid and cold dry air in a new
      model of anesthetized, mechanically ventilated guinea pigs, and to compare
      findings with known effects in humans. Intratracheal air (T(tr)) and
      retrotracheal tissue (T(oe)) temperatures and peak expiratory airflow (PEF),
      tidal volume (V(T)), heart rate, and blood pressure of hyperventilating animals
      were measured continuously. Four consecutive 10-min exposures to warm humid air
      (n = 7) produced slight airway warming and minimal lung function changes during
      the exposure. In a single 10-min exposure to cold dry air (n = 39), T(tr)
      decreased from (means +/- SEM) 36.1 +/- 0.3 degrees C to 26.3 +/- 0.3 degrees C
      (Delta = -9.8 +/- 0.4 degrees C) and T(oe) from 36.4 +/- 0.2 degrees C to 35.5 +/
      0.2 degrees C (Delta = -0.9 +/- 0.1 degrees C). PEF and V(T) decreased in
      response to airway cooling with maximal decrements within the first 2-4 min from
      the beginning of the exposure period. The maximal decrease in PEF was from 21.7
      +/- 0.3 ml s(-1) to 15.9 +/- 0.5 ml s(-1) (Delta = -26.7%) and that in V(T) from
      5.2 +/- 0.1 ml to 4.2 +/- 0.1 ml (Delta = -19.2%) (p <.05 for both changes). The
      decreases in lung functions attenuated significantly during the course of the 10
      min exposure to cold dry air, indicating adaptation. Consequently, the decrements
      in PEF and V(T) at 5, 7.5, and 10 min were significantly smaller than those at 3
      min. In four consecutive 10-min exposures to cold dry air (n = 15), there were no
      statistically significant differences in T(tr) or T(oe) decreases between the
      exposure periods. The largest decreases in the lung function parameters were
      during the first exposure period, whereas there were significantly smaller
      responses during the second and third exposure periods (p <.05). Thus, a highly
      reproducible airway cooling and an immediate bronchoconstriction were produced in
      response to cold dry air hyperventilation in guinea pigs. During the course of
      cold-air exposure and in repeated exposures, there was a significant attenuation
      of the bronchial response, which resembled the refractoriness of the asthmatic
      airways to repeated hyperventilation of cold or warm dry air. The present guinea
      pig model seems to be well suited for production of complementary animal data on
      the pathophysiological effects of cold dry air on the tracheobronchial airways.

PMID- 10880151
TI  - Combined respiratory effects of cold air with SO(2) or NO(2) in repeated 10
      minute exposures of hyperventilating guinea pigs.
AB  - Previous studies in asthmatic subjects and guinea pigs have demonstrated
      attenuation of bronchoconstriction in repeated exposures to clean cold dry air.
      In the present animal study, we have simulated short-lasting human exposures to
      subfreezing urban air containing sulfur dioxide (SO(2)) and nitrogen dioxide
      (NO(2)). The anesthetized, paralyzed, and mechanically ventilated guinea pigs had
      4 consecutive 10-min exposures either to clean cold dry air or to cold air with
      graded concentrations of SO(2) (0-5 ppm) or NO(2) (0-4 ppm). Peak expiratory flow
      (PEF) and tidal volume (V(T)) were continuously measured both during and after
      highly controlled exposures. Bronchoalveolar lavage fluid (BALF) and histological
      samples were obtained after finishing the consecutive exposures. Cold air + SO(2)
      at 1 and 2.5 ppm (n = 12) produced immediate concentration-dependent increases in
      the lung function responses compared to the preceding single exposure to clean
      cold dry air in the same animals (DeltaPEF = -32.7 +/- 6.1% and -35.6 +/- 6.5%
      vs. -27.0 +/- 3.1%; DeltaV(T) = -22.4 +/- 4.4% and -28.3 +/- 4.7% vs. -18.1 +/-
      2.9%). In a multivariate analysis, these responses were significantly larger than
      the attenuated lung function responses to the corresponding second and third
      clean cold dry air exposures (p <. 05). The fourth exposure to cold air + SO(2)
      at 5 ppm produced a smaller response (DeltaPEF = -25.3 +/- 4.8% and DeltaV(T) = 
      17.8 +/- 3.7%) than cold air with the lower SO(2) concentrations. Cold air +
      NO(2) at 1 and 2.5 ppm (n = 12) produced roughly similar lung function responses
      to the preceding single exposure to clean cold dry air in the same animals, and
      there was no significant attenuation of bronchoconstriction as with the
      consecutive exposures to clean cold dry air. The largest decreases in lung
      functions (DeltaPEF = -33.8 +/- 6.7% and DeltaV(T) = -26.2 +/- 6.8%) were
      recorded during the fourth exposure, which was to cold air + NO(2) at 4 ppm. In
      the cold air + SO(2) group, there was a significantly lower proportion of
      macrophages in the differential count of BALF white cells compared to the clean
      cold dry air group. In addition, there was eosinophilic infiltration within and
      below the tracheal epithelium in all guinea pigs exposed to either clean cold dry
      air, cold air + SO(2), or cold air + NO(2). In conclusion, the addition of
      moderate concentrations of SO(2) or NO(2) to clean cold dry air counteracted the
      attenuation of bronchoconstriction induced by repeated cold dry air exposures in
      guinea pigs. Cold air + SO(2) also decreased the proportion of macrophages in
      BALF white cells.

PMID- 10880152
TI  - Combined respiratory effects of cold air with SO(2) or NO(2) in single 1-hour
      exposures of hyperventilating guinea pigs.
AB  - The present study is a continuation of our previous experiments on repeated 10
      min exposures of anesthetized, mechanically ventilated guinea pigs to clean cold
      dry air (Halinen et al., 2000a), and to cold air plus gaseous air pollutants
      (Halinen et al., 2000b). This time we made continuous 60-min exposures to clean
      cold dry air, cold air + SO(2) at 1 ppm, cold air + NO(2) at 1 ppm, and warm
      humid air + NO(2) at 1 ppm, and focused on responses at 10-60 min. Clean cold dry
      air and cold air + pollutants (n = 8-9 in each group) produced similar cooling in
      the guinea pig lower respiratory tract. The decreases in intratracheal
      temperature (T(tr)) reached a plateau at 20 min with mean maximal decreases of
      9.7-11.3 degrees C from the pre-exposure control values of 36.0-37.3 degrees C.
      In contrast, there were progressive decreases in esophageal temperature (T(oe))
      during the exposures, indicating constant conductive and evaporative heat losses
      from the tracheobronchial tissues. The mean maximal decreases in T(oe) were 1.2
      1.4 degrees C from the preexposure control values of 37.8-38.0 degrees C. Clean
      cold dry air induced 4. 5-10.8% mean decreases in peak expiratory flow (PEF) at
      10-60 min of exposure, which were statistically nonsignificant due to a
      relatively large variation between animals. Cold air + SO(2) at 1 ppm induced a
      mean decrease of 11.4% in PEF at 10 min (p <.05), which was spontaneously
      abolished during the next 10 min of exposure. Cold air + NO(2) at 1 ppm caused no
      decrease, but in fact small, nonsignificant increases in PEF at 30-60 min of
      exposure. Cold air + NO(2) at 1 ppm, and to some extent also cold air + SO(2) at
      1 ppm, attenuated significantly the mechanical ventilation induced gradual
      decrease in tidal volume (V(T)), when compared to clean cold dry air exposure.
      Cold air + NO(2) at 1 ppm, but not warm humid air + NO(2) at 1 ppm, increased
      significantly the proportion of macrophages in the differential count of
      bronchoalveolar lavage fluid (BALF) white cells when compared to both clean warm
      humid air and cold dry air. None of the exposure conditions caused morphological
      or inflammatory changes in the respiratory tissues. In conclusion, continuous 60
      min exposures to clean cold dry air, cold air + SO(2), and cold air + NO(2)
      produced weaker functional effects on the lower respiratory tract of guinea pigs
      than our previous consecutive 10-min exposures to these air conditions. After the
      first 10 min, there was a strong attenuation of the bronchoconstrictor responses,
      especially to cold air + NO(2) at 1 ppm. The small airway effects of prolonged
      mechanical ventilation were significantly modified by NO(2) at 1 ppm in both cold
      dry and warm humid breathing air. Finally, cold air + NO(2) at 1 ppm increased
      the proportion of macrophages in BALF white cells.

PMID- 10880153
TI  - Measurement of total lung deposition of inhaled ultrafine particles in healthy
      men and women.
AB  - Ultrafine particles (< 0.10 microm in diameter) are present in great number in
      polluted urban air, thus posing a potential health risk. In this study, the total
      deposition fraction (TDF) of ultrafine aerosols with a narrow size distribution
      (number median diameter NMD = 0.04-0.1 microm and geometric standard deviation
      sigma(g) = approximately 1.3) was measured in a group of young healthy adults (11
      men and 11 women). TDF was obtained with 6 different breathing patterns: tidal
      volume (V(t)) of 500 ml at respiratory flow rates (Q) of 150 and 250 ml/s; V(t) =
      750 ml at Q of 250 and 375 ml/s; and V(t) = 1 L at Q of 250 and 500 ml/s.
      Aerosols were monitored continuously by a modified condensation nuclei counter
      while subjects were inhaling them with prescribed breathing patterns. For a given
      breathing pattern, TDF increased as particle size decreased, regardless of the
      breathing pattern used. For example, with V(t) = 500 ml and Q = 250 ml/s, TDF
      (mean +/- SD) was 0.26 +/-.04, 0.30 +/-. 05, 0.35 +/-.05, and 0.44 +/-.07 for NMD
      = 0.10, 0.08, 0.06, and 0. 04 microm, respectively. For a given NMD, TDF
      increased with an increase in V(t) and a decrease in Q. TDF was greater for women
      than men at NMD = 0.04 microm within all breathing patterns used (p <.05), but
      the difference was smaller or negligible for larger sized particles. The results
      suggest that the TDF of ultrafine particles increases with a decrease of particle
      size and with breathing patterns of longer respiratory time, a pattern that is
      consistent with diffusion deposition of ultrafine particles. The results also
      suggest that there is a differential lung dose of ultrafine particles and thus
      there may be a differential health risk for men versus women.

PMID- 10880154
TI  - Particle clearance and histopathology in lungs of C3H/HeJ mice administered
      beryllium/copper alloy by intratracheal instillation.
AB  - Beryllium/copper (BeCu) alloys are commonly used in the electronics, automotive,
      consumer, defense, and aerospace industries. Some individuals exposed
      occupationally to BeCu alloys have developed chronic beryllium disease. However,
      little is known of the toxicity and fate of BeCu alloys in the respiratory tract.
      To begin to address this question, we investigated the pulmonary toxicity and
      clearance of BeCu alloy (2% Be; 98% Cu) in mice. Groups of 40 female C3H/HeJ mice
      were administered 12.5, 25, and 100 microg BeCu alloy or 2 and 8 microg Be metal
      by intratracheal instillation. Mice were sacrificed at 1 h and 1, 7, 14, and 28
      days postinstillation. Left lungs were evaluated for histopathological change.
      Right lungs were analyzed for Be and Cu content. Twenty-five percent of the high
      dose BeCu mice and 7.5% of the mid-dose BeCu mice died within 24 h of dosing.
      Acute pulmonary lesions included acute alveolitis and interstitial inflammation.
      Type II epithelial cell hyperplasia and centriacinar fibrosis were present by 7
      days after dosing. Lesions persisted through 28 days after instillation. No
      lesions attributable to alloy exposure were present in liver or kidney. Be metal
      instillation caused no deaths and minimal pulmonary changes over the time
      studied, indicating that the pulmonary lesions were due to Cu rather than Be. Cu
      cleared the lung with a half-time of 0. 5-2 days. Be cleared with a half-time of
      several weeks or longer. Results of this study suggest that exposure to BeCu
      alloy is more acutely toxic to lung than Be metal. The results of tissue analyses
      also indicate that, while the Cu component of the alloy clears the lung rapidly,
      Be is retained and may accumulate upon repeated exposure.

PMID- 10880155
TI  - Setting safe acute exposure limits for halon replacement chemicals using
      physiologically based pharmacokinetic modeling.
AB  - Most proposed replacements for Halon 1301 as a fire suppressant are halogenated
      hydrocarbons. The acute toxic endpoint of concern for these agents is cardiac
      sensitization. An approach is described that links the cardiac endpoint as
      assessed in dogs to a target arterial concentration in humans. Linkage was made
      using a physiologically based pharmacokinetic (PBPK) model. Monte Carlo
      simulations, which account for population variability, were used to establish
      safe exposure times at different exposure concentrations for Halon 1301
      (bromotrifluoromethane), CF(3)I (trifluoroiodomethane), HFC-125
      (pentafluoroethane), HFC-227ea (1,1,1,2,3,3,3-heptafluoropropane), and HFC-236fa
      (1,1,1,3,3,3-hexafluoropropane). Application of the modeling technique described
      here not only makes use of the conservative cardiac sensitization endpoint, but
      also uses an understanding of the pharmacokinetics of the chemical agents to
      better establish standards for safe exposure. The combined application of cardiac
      sensitization data and physiologically based modeling provides a quantitative
      approach, which can facilitate the selection and effective use of halon
      replacement candidates.

PMID- 10880156
TI  - Intracellular surfactant removal from phagocytized minerals: development of a
      fluorescent method using a BODIPY-labeled phospholipid.
AB  - Lung surfactant serves as a protective coating when adsorbed on particle
      surfaces, so its removal or rate of removal in vivo may affect expression of
      mineral cytotoxicity. Removal of phospholipid surfactant components from the
      surface of mineral particles ingested by alveolar macrophages (AM) was measured
      using fluorescence microscopy. Dipalmitoylphosphatidylcholine with a fluorescent
      label (BODIPY(trade mark)) substituted for C1-C4 on the second acyl chain
      (DPPC*), was mixed with dioleoylphosphatidylcholine (DOPC) to coat respirable
      quartz and kaolin particles. Fluorescence from quartz or kaolin particles of 3-4,
      5-6 and 8-9 microm size decreased in intensity with increasing ratios of
      DOPC/DPPC* for the same DOPC concentration of 0.4 mg/ml. There was a direct
      correlation between fluorescence and residual phospholipid surfactant remaining
      on particles using phospholipase A2 (PLA(2)) digestion in a cell-free system,
      indicating that the presence of the fluorophore on DPPC did not hinder enzymatic
      recognition. Lavaged primary AM obtained from male Fischer rats were challenged
      in vitro with DOPC/DPPC* (10:1 mol:mol) coated particles at 50 microg
      particles/10(6) cells. In contrast to the biexponential response seen in cell
      free experiments, the rate of fluorescence decay from ingested coated quartz or
      kaolin particles over 7 days was monoexponential, with the same t(1/2) (41 h) for
      each dust. This study suggests that the rate of phagolysosomal digestion and
      removal of the adsorbed surfactant is not a determinant of the different mineral
      specific pathogenicities or toxicities of quartz and kaolin, although residual
      fluorescence remained on particles even after 7-8 days.

PMID- 10880157
TI  - Differential diagnosis between hepatic focal nodular hyperplasia and
      hepatocellular carcinoma with negative alhpa-fetoprotein.
AB  - OBJECTIVE: To study the differential diagnosis between hepatic focal nodular
      hyperplasia (FNH) and hepatocellular carcinoma (HCC) with negative alpha-feto
      protein. METHODS: To analyse retrospectively the clinical and imaging materials
      of 18 patients with FNH and 254 patients with AFP negative HCC proven by
      operation and pathology during March 1996 to March 1999 in our institute.
      RESULTS: Patients with FNH were largely younger (66.7% under 40 years),
      discovered accidentally (66.7%), and without hepatitis background (83.3%).
      Majority of them had a normal liver function (72.0%). A big central artery was
      found in the lesion with high velocity and low resistant index in 71.4% of
      patients by color Doppler ultrasound. CT scan showed transient immediate
      enhancement in 85.7% of patients after bolus injection, being homogeneous (53.3%)
      and isodensity (73.3%) in the portal vein phase. MR imaging demonstrated early
      vigorous enhancement (83.3%) and homogenous (66.7%) lesion. In contrast, patients
      with AFP negative HCC were generally older (85.8% over 40 years), with symptoms
      (74.0%). A color flow with high velocity and high resistant index was found by
      color Doppler ultrasound. CT scan showed early heterogenous enhancement (96.6%)
      after bolus injection and being hypodensity in portal vein phase. MR imaging
      indicated early heterogeneous enhancement (91.7%). CONCLUSION: FNH shows some
      typical clinical and imaging features. Therefore, it is feasible to be
      differentiated from HCC with negative AFP in some of the patients.

PMID- 10880158
TI  - The value of serum GPDA-F for the diagnosis of primary hepatocellular carcinoma.
AB  - OBJECTIVE: To investigate the role of glycylproline dipeptidyl aminopeptidase
      isoenzymes in the diagnosis of primary hepatocellular carcinoma (PHC). METHODS:
      We developed a stage gradient polyacrylamide gel electrophoresis system to
      separate serum GPDA isoenzymes. Total GPDA activities, alpha-fetoprotein, the
      sizes of tumors and alanine aminotransferase (ALT) activities were also measured
      simultaneously and the correlation between GPDA-F and these indices was analyzed.
      RESULTS: Serum GPDA was separated into two bands, namely fast band (GPDA-F) and
      slow band (GPDA-S). GPDA-F was negative in all healthy persons as well as in the
      patients with benign liver filling defects, while it was positive in 85.3% cases
      of PHC. Liver cirrhosis, chronic hepatitis, extrahepatic carcinoma and metastatic
      liver carcinoma had low positive rates. GPDA-F was positively correlated with
      serum total GPDA activities, but had no correlation with AFP and size of the
      tumors. There was the correlation between GPDA-F and ALT in benign liver
      diseases, but no correlation between GPDA-F and ALT in PHC. Serial measurements
      of serum GPDA-F showed that GPDA-F was persistently positive in PHC but might
      change into negative in benign liver diseases. Dynamic determination of GPDA-F
      might be helpful to differentiate true positive of PHC from false positive of
      benign liver diseases. CONCLUSION: GPDA-F is a new serum marker of PHC.
      Measurement of serum GPDA-F is of value for the diagnosis of PHC, especially for
      those at early stage or with negative AFP.

PMID- 10880159
TI  - Effects of hepatic artery chemotherapeutic embolization combined with perfusing
      LAK cells into hepatic artery after radical operation of liver cancer.
AB  - OBJECTIVE: To evaluate the effects of hepatic artery chemotherapeutic
      embolization combined with perfusing LAK cells/interleukin 2 into hepatic artery
      after radical operation of liver cancer. METHODS: Random divide 42 cases into two
      groups who had accepted radical operation of liver cancer: 21 cases who accepted
      hepatic artery chemotherapeutic embolization combined with perfusing LAK
      cells/interleukin 2 into hepatic artery as observing group, 21 cases accepted
      simply hepatic artery chemotherapeutic embolization as control group. RESULTS:
      The intrahepatic recurrence rates of 1, 2, and 3 years were 0, 19.05%, 57.14% in
      observing group, lower than 28.57%, 47.62%, 85.71% of control group (chi(2)=4.86,
      3. 86 and 4.20 respectively, P<0.05). The survival rates of 2 and 3 years were
      85.71%, 61.90% in observing group, higher than 57.14%, 28. 57% of control group
      (chi(2)=4.20 and 4.71, P<0.05). CONCLUSION: Hepatic artery chemotherapeutic
      embolization combined with perfusing LAK cells/interleukin 2 into hepatic artery
      is an effective therapeutic method to control intrahepatic recurrence rates and
      raise the survival rates of the patients.

PMID- 10880160
TI  - Gene variation of 5'-NCR and core region in serum samples collected from patients
      with HCV infection.
AB  - OBJECTIVE: To study the variation of HCV 5'-NCR and core gene in serial sera
      collected from patients with HCV infection. METHODS: Serial sera were collected
      from 4 plasma-donors with HCV infection. 5'-NCR and core gene were amplified,
      sequenced and analyzed using software. RESULTS: All the sequences obtained from
      the serial sera of patients with HCV infection were 1b and 2a subtypes. The
      variation of 5'-NCR only related to the genotype, and not associated with
      patients and time of serum collection. However, the sequences of core gene were
      not identical in HCV strains isolated from different patients. The sequences of
      those two regions of the same genotype isolated from the same patient did not
      change with time. CONCLUSION: 5'-NCR is more conserved than the core region and
      the genotype is the major cause of gene variation. No change in sequences of
      those two regions is found at the different points of time.

PMID- 10880161
TI  - Detection of transfusion transmitted virus in hepatic and extra hepatic tissues
      using in situ hybridization.
AB  - OBJECTIVE: To investigate the location, distribution and significance of
      transfusion transmitted virus (TTV) in the liver and extra hepatic tissues.
      METHODS: A 123 bp fragment of TTV DNA within ORF(2) was amplified by PCR reaction
      and cloned into PCR2.1 vector. DNA sequencing revealed that the inserted fragment
      was highly isogenous with Japan ABO11494 strain. The inserted fragment was
      labeled with digoxigenin. Segment of liver, spleen, kidney, stomach and intestine
      tissues from 22 patients dead of liver diseases were detected by in situ
      hybridization with this digoxigenin labeled TTV DNA probe. RESULTS: TTV DNA was
      detected in 8 livers, 4 kidneys, 3 spleens, 2 intestines, and 2 stomachs. The
      positive cells of TTV DNA in livers were higher than that in other tissues. No
      obvious pathological topographical relationship of tissue inflammatory reaction
      with positive cells was found. CONCLUSION: TTV can infect hepatic and ex-hepatic
      tissues and may cause persistent infection.

PMID- 10880162
TI  - Expression of vascular endothelial growth factor in liver tissues of hepatitis B.
AB  - OBJECTIVE: To study the relationship between vascular endothelial growth factor
      (VEGF) and grading (G) and staging (S) of hepatitis B (HB). METHODS:
      Immunohistochemical staining was performed with VEGF monoclonal antibody in 250
      biopsies of HB. RESULTS: The types of VEGF expression in liver tissues were of
      plasma type, sinusoidal membrane type and sinusoidal endothelial cell type. VEGF
      was mainly secreted by hepatocytes, and was also positively expressed in liver
      sinusoidal endothelial cells, fat-storing cells, myofibroblast and
      monomorphological nuclear cells. And it was negative in vascular endothelial
      cells and hepatocytes which had not significant damage, suggesting that the
      expression of VEGF was enhanced with the increase of G (chi(2)=90.43, P<0.01).
      VEGF was positively expressed on those whose scores of S were lower, while
      strongly positively expressed on those whose scores of S were higher. There was
      also a significant difference between them (chi(2)=115.74, P<0.01). CONCLUSION:
      The expressions of VEGF are related to G and S of HB

PMID- 10880163
TI  - Cloning and sequencing of partial genes of hepatitis C virus genome in patients
      with acute hepatitis C.
AB  - OBJECTIVE: To explore the etiological role of HCV in patients with acute
      hepatitis. METHODS: The prevalence of HCV infection in 89 patients with acute
      hepatitis was investigated by analysis of HCV RNA and HCV second generation
      antibody. HCV RNAs extracted from the sera of 5 patients with NANB acute
      hepatitis, which were positive for HCV RNA, were converted to cDNA by reverse
      transcription with random primer and genotyping by PCR with type-specific
      primers. The partial genes of HCV genome were amplified. The PCR products were
      expressed in E. coli with p-GEM-T vector, and their nucleotide sequences were
      determined by dideoxynucleotide chain-termination method. RESULTS: The incidence
      of hepatitis virus infection was 47. 2% in HAV, 28.1% in HBV and 15.7% in HCV,
      respectively. The incidence of HAV and HBV coinfection was 14.6% and the rate of
      non-A, non-B and non-C hepatitis was 9% in all patients. The genotype of HCV-RNA
      positive patients was 85.8% in HCV-II, 7.1% in HCV-III and 7. 1% in combining HCV
      II/III, respectively. The partial sequence of HCV genome in 5 patients with non-A
      and non-B acute hepatitis was amplified and the fragment was 424 bp in accordance
      with original design. The homology of the sequences was 98.1%-99.5% in nucleotide
      acid and 97.6%-99.2% in amino acid among five isolates. The average homology was
      91.9% or 94.3%-95.6% for nucleotide sequences between HCV-I or HCV-II and the 5
      isolates, and 92.3%-95.8% for amino acid sequences between the 5 isolates and HCV
      I or HCV-II, respectively. CONCLUSION: HCV infection is one of the main hepatitis
      viruses in patients with acute hepatitis, in which the HCV-II genotype is
      dominant and should be paid attention to it.

PMID- 10880164
TI  - Measurement and significance of oblique occipital frontal diameter and superior
      inferior diameter of hepatic left lobulus in patients with hepatic fibrosis.
AB  - OBJECTIVE: To study the changes and significance of oblique occipital frontal
      diameter (OFD) and superior inferior diameter (SID) of the hepatic left lobulus
      in different stages of hepatic fibrosis, and to evaluate the value of
      corresponding serological examination in the non-invasive diagnosis to hepatic
      fibrosis and cirrhosis. METHODS: Seventy-two patients with chronic hepatitis were
      confirmed by biopsy. OFD and SID of the hepatic left lobulus were measured by
      type B ultrasonic flaw detector. Serum levels of hyaluronic acid (HA), laminin
      (LN), type IV collagen (CIV) and type III procollagen (PCIII) were measured by
      radioimmunoassay. RESULTS: SID of the hepatic left lobulus in S(4) stage was
      5.7cmA1.5cm, significantly shorter than the values of 7.7cmA1.4 cm in S(0) stage.
      OFD of the hepatic left lobulus was longer in S(4) stage than S(0) stage, but the
      difference didn't reach statistical significance. Serum levels of HA, LN,CIV, and
      PCIII elevated as the increase of fibrosis. HA and PCIII increased to
      273.4mug/LA131.3mug/L and 167. 4mug/LA48.1mug/L in S3 stage from
      66.2mug/LA35.0mug/L and 103. 4mug/LA23.8mug/L in S(0) stage. CONCLUSION: Changes
      in of SID and OFD of the hepatic left lobulus and serum levels of HA and PCIII
      may indicate indirectly mid-late hepatic fibrosis or early cirrhosis.

PMID- 10880165
TI  - A trial of ademetionine in the treatment of intrahepatic biliary stasis viral
      hepatitis.
AB  - OBJECTIVE: To observe the efficacy and safety of ademetionine in the treatment of
      viral hepatitis with intrahepatic biliary stasis. METHODS: In this series, 110
      patients with viral hepatitis associated intrahepatic biliary stasis were
      randomly divided into Groups A and B. Patients in Group A received ademetionine
      for four weeks. Patients in Group B received potassium magnesium aspartate for
      four weeks. RESULTS: In Group A, at the end of treatment, the effective rate for
      skin pruritus in patients with cholestatic hepatitis was 86.67% (13/15), and the
      effective rate for skin pruritus and anorexia were 88.24% (15/17) and 82.35%
      (14/17), respectively in patients with chronic hepatitis combining intrahepatic
      cholestasis, which were significantly higher than that in Group B (P<0.05). STB,
      SCB, TBA, ALT and AST were lower in Group A than Group B (P<0.05). The decrease
      of ALP and the increase of albumin after treatment were more significant in Group
      A than in Group B (P<0.05). CONCLUSION: Ademetionine has better efficacy than
      potassium magnesium aspartate in the treatment of patients with cholestatic viral
      hepatitis.

PMID- 10880166
TI  - Hepatitis B virus X protein activates expression of IGF-IR and VEGF in
      hepatocellular carcinoma cells.
AB  - OBJECTIVE: The expression of insulin-like growth factor I receptor (IGF-IR) and
      the vascular endothelial growth factor (VEGF) in HepG(2) cells transfected with a
      hepatitis B virus X (HBx) expression vector was investigated in an attempt to
      study their possible relationship to the growth of HBx-induced hepatocellular
      carcinoma (HCC). METHODS: The eucaryotic expression vector of HBx gene was
      constructed and introduced into HepG(2) cells. The modified cell HepaG(2)-X was
      synchronized in a quiescent state by culture of serum deprivation. The IGF-IR and
      VEGF were analyzed by immunohistochemical and Western blot technique. RESULTS:
      The positive rate of IGF-IR expression was 84%A3% in the transfected HBx gene
      cells, 26%A4% in X(0) control cells. The positive rate of VEGF expressed x cells
      was 83%A5%, X(0) cells was 28%A6% (P<0.001). The level of IGF-IR and VEGF in
      serum-starved x modified cells was 1.5 times higher than that of synchronized
      X(0) modified cells. CONCLUSION: Since the IGF-IR is a very important growth
      factor in sustaining the tumor abnormal growth and the VEGF has a crucial role in
      inducting tumor angiogenesis, our findings indicate that HBx may play an
      important role in the processes of HCC by activating IGF-IR and VEGF gene
      expression.

PMID- 10880167
TI  - Effects of lipid on low-density and high-density lipoprotein receptors in hepatic
      stellate cell from rat liver.
AB  - OBJECTIVE: To study the effects of lipid (triglyceride and very low-density
      lipoprotein) on low-density lipoprotein (LDL) and high-density lipoprotein (HDL)
      receptors in the hepatic stellate cell (HSC) from the rat liver. METHODS: HSC
      were isolated and cultured from the liver of Wistar rats by in situ perfusion
      with pronase and collagenase and density gradient centrifugation with Nycodenz.
      Radioligand conjugation assay with (125)I-LDL and (125)I-HDL(3) was detected for
      the effects of lipid on LDL and HDL receptor of HSC. RESULTS: LDL and HDL
      receptors were found on the membrane of the rat HSC. The lipid might increase the
      binding of LDL to LDL receptor, but decrease the binding of HDL(3) to HDL
      receptor. CONCLUSION: LDL and HDL receptors on the HSC membrane may have an
      important role in the metabolism of lipoprotein and the regulation of
      cholesterol. These results provided the basis of theory and experimentation for
      the genesis of fatty liver and liver fibrosis.

PMID- 10880168
TI  - Selecting anti-HBsAg fab phage antibodies from the phage antibody library.
AB  - OBJECTIVE: Selecting Fab phage antibodies to HBsAg from the phage antibody
      library. METHODS: The phages displaying antibody fragments were subjected to
      three rounds of panning with HBsAg coated in solid phase. RESULTS: The eluted
      phages were enriched nearly 80-fold, and the percentage of recombinant clones
      increased from 17% to 100% after the third round of panning. The HBsAg specific
      monoclonal antibodies were determined by ELISA. These antibodies combined
      specifically with HBsAg, but not with BSA and HAV antigens. CONCLUSION: Our work
      on constructing human immunoglobulin combinatorial library and selecting anti
      HBsAg Fab phage antibodies would be beneficial to the further study on the
      production of soluble Fab antibodies.

PMID- 10880169
TI  - Anti-HBV effect of targeted antisense RNA against HBV C gene.
AB  - OBJECTIVE: To investigate the anti-HBV effect of targeted antisense RNA to
      hepatic cells. METHODS: pREP4-aC which would transcript antisense RNA against HBV
      C gene in eukaryotic cells were delivered into 2.2.15 cells by glactosylated poly
      L-lisine (Gal-PLL), and the positive cells were selected. HBsAg, HBeAg and HBV
      DNA produced by 2. 2.15 cells were detected with ELISA or Southern blot during
      the experiment, and the cytotoxicity of targeted antisense on 2.2.15 cells was
      observed. RESULTS: The inhibition effect on HBsAg, HBeAg and HBV DNA occurred at
      the 24th hour after delivery and reached the highest level at the 6th day, and
      kept at lest two months. No cytotoxicity on 2.2.15 cells was observed.
      CONCLUSION: The targeted antisense against HBV C gene by delivery of Gal-PLL
      could effectively inhibit the antigen expression of HBV and DNA replication.

PMID- 10880170
TI  - Expression of human single-chain variable fragment antibody against non
      structural protein 3 of hepatitis C virus antigen in e.coli.
AB  - OBJECTIVE: To express human single-chain variable fragment (ScFv) antibody
      against non-structural protein 3 (NS(3)) of hepatitis C virus in E.coli. METHODS:
      The recombinant phages were panned by NS(3) antigen which was coated in a
      microtiter plate. After five rounds of biopanning, 66 clones were identified
      specific to NS(3) antigen. E.coli host XL(1)-Blue was transformed and induced by
      IPTG. The specificity of ScFv was evaluated by ELISA and dot blot hybridization.
      RESULTS: ScFv-NS(3) DNA digestion and sequencing data showed that the ScFv gene
      was composed of 750bp. ELISA and dot blot hybridization demonstrated that the
      soluble human single-chain Fv antibody to hepatitis C virus NS(3) antigen could
      combine different origins of NS(3) antigen. CONCLUSION: NS(3)-ScFv antibody
      expressed by E.coli host XL(1)-Blue has the activity and specificity to combine
      different origins of HCV NS(3) antigen.

PMID- 10880171
TI  - Effects of intestinal endotoxemia on pathogenesis of liver injury induced by
      thioacetamide.
AB  - OBJECTIVE: To study the effect of intestinal endotoxemia on pathogenesis of liver
      injury induced by thioacetamide (TAA). METHODS: Twenty-six male Wistar rats were
      divided into 4 groups, namely: normally control group (N), colectomy control
      group (C), colectomy+TAA group (C+T), TAA group (T). The changes in plasma
      biochemistry were measured. RESULTS: Plasma endotoxin levels were significantly
      higher in TAA group than normally control group. Plasma endotoxin levels in
      colectomy+TAA group were close to that of normally control group. Plasma ALT
      activity in colectomy+TAA group increased significantly compared with that of
      normal control group, but markedly lower than that in TAA group. Plasma endotoxin
      levels were positively correlated to ALT activity in T and C+T groups (r=0. 985,
      P<0.01). CONCLUSION: TAA itself has a deleterious effect to hepatic cells. It can
      also induce intestinal endotoxemia in which the liver injury is more inclined to
      occur and severe.

PMID- 10880172
TI  - Traumatic medial malleolar fracture of a fibula flap donor leg.
AB  - A 50-year-old male presented with a T4 N0 squamous cell carcinoma of the floor of
      the mouth and alveolus. Treatment included a partial mandibulectomy with a free
      osseocutaneous fibula flap reconstruction. He made a good postoperative recovery
      and was given adjuvant radiotherapy. No problems were reported with the donor
      site or ankle. Five months after harvesting the flap the patient sustained a
      fracture of the medial malleolus having jumped over a ditch playing golf. This
      was treated successfully with a below knee plaster of Paris cast. The
      interosseous membrane was not ruptured in the accident indicating that the distal
      fibula left in situ was adequate to maintain the integrity of the mortice. A
      degree of ankle instability may be present after fibula flap harvest which is
      only revealed by athletic activity. (c) 2000 Harcourt Publishers Ltd Copyright
      2000 The British Association of Plastic Surgeons DOI: 10.1054/bjps.1999.3227.

PMID- 10880173
TI  - Simultaneous avulsion fracture of the insertion of the ulnar and radial
      collateral ligaments of the metacarpophalangeal joint of the thumb.
AB  - We present a case of simultaneous avulsion fracture of the insertion on the volar
      base of the proximal phalanx of the ulnar and radial collateral ligaments of the
      metacarpophalangeal joint of the thumb. To our knowledge this combination has
      never been published before. The mechanism of this injury is not clearly
      understood. (c) 2000 Harcourt Publishers Ltd Copyright 2000 The British
      Association of Plastic Surgeons DOI: 10.1054/bjps.1999.3227.

PMID- 10880174
TI  - The public health significance of VTEC O157.
AB  - Surveillance of human VTEC O157 has been reported in several countries, based on
      laboratory evidence. The incidence is generally less than 10 per 100000 (the
      highest incidence is in children), with regional variations and a marked
      seasonality. Laboratory selection criteria and reporting have contributed to, but
      cannot entirely explain, variations within and between countries. Surveillance
      data and outbreaks in definable cohorts indicate that the spectrum of illness
      ranges from diarrhoea through acute bloody diarrhoea, with about 5% of cases
      developing haemolytic uraemic syndrome; less than 50% of patients report frank
      blood in their stools. Studies of sporadic cases have associated illness with
      beef products (particularly if undercooked and eaten outside the home), cooked
      sliced meat meals and contact with a household member with diarrhoea. Outbreaks
      have been attributed to contaminated foods (including beefburgers) and water,
      animal contact and person-to-person spread. Secondary transmission by the primary
      case in a household is of particular concern, and household transmission has been
      estimated at 4%, with patients excreting for around 10 days following onset.
      Recommendations for control have highlighted measures on farms, in
      slaughterhouses, retail and catering food premises, and in the home.

PMID- 10880175
TI  - VTEC enteropathogenicity.

PMID- 10880176
TI  - Clinical presentation, complications and treatment of infection with
      verocytotoxin-producing Escherichia coli. Challenges for the clinician.
AB  - Seventeen years after its recognition, outbreaks and sporadic infections
      attributed to Escherichia coli O157 continue to increase. Acute gastrointestinal,
      and the systemic complications haemolytic uraemic syndrome (HUS) and thrombotic
      thrombocytopenic purpura (TTP), are frequent and severe. Current challenges that
      face clinicians are the early recognition of infection, identification of risk
      factors for poor prognosis, determination of appropriate monitoring for the
      development of complications, establishment of a therapeutic strategy and,
      finally, advice for patients about their long-term prognosis. Clinical features
      which, in combination, have been shown to distinguish E. coli O157 infection from
      other enteric pathogens are a history of bloody diarrhoea, visibly bloody stools,
      absence of fever, a leucocyte count greater than 10 x 10(9) l(-1) and abdominal
      tenderness on physical examination. The most consistent risk factors for the
      development of HUS/TTP are the extremes of age and a raised leucocyte count.
      Bloody diarrhoea and 'antimotility' drugs are also likely to be important risk
      factors. Recent evidence from the central Scotland outbreak suggests that
      individuals who are taking drugs that reduce gastric acidity or antibiotics at
      the time of infection with E. coli O157, or who have a short incubation period,
      may also be at increased risk of progression to HUS/TTP. Clinical management, in
      particular the role of antibiotics in gastrointestinal infection, remains
      controversial, and retrospective assessment of the 1996 outbreaks from central
      Scotland and Japan only adds to this controversy. Therapeutic plasma exchange is
      a promising treatment for adults who develop HUS/TTP, but its role has yet to be
      determined definitively, either in a randomized controlled trial or by an
      international register of cases. Significant chronic sequelae of infection occur,
      particularly irritable bowel syndrome after uncomplicated gastrointestinal
      infection, and renal failure after HUS/TTP. Their frequency and severity are
      likely to become evident over the next decade.

PMID- 10880177
TI  - Verocytotoxin-producing Escherichia coli: a veterinary view.
AB  - This overview places verocytotoxin-producing Escherichia coli (VTEC) in
      perspective with other E. coli types that cause disease in animals. VTEC O157 and
      other verocytotoxin-producing serotypes cause severe disease in man but to date,
      although other VTEC are found in animals, zoonosis appears to be associated with
      E. coli O157 only. The epidemiology of E. coli O157 in cattle has been studied in
      Scotland, and this work is described alongside current knowledge.

PMID- 10880178
TI  - Role of non-O157 VTEC.
AB  - Non-O157 VTEC are typical Escherichia coli that differ only in their ability to
      produce verocytotoxins (VT). The transmission of VTEC is discussed in relation to
      the transmission of commensal E. coli. The emergence over the last few decades of
      a great variety of VTEC serotypes from healthy and diseased humans and animals is
      described. Particular attention is given to the distribution of the more
      important serogroups pathogenic for humans that have been described from around
      the world, particularly serogroups O26, O111, O128 and O103. The possible role of
      ruminants as reservoirs is discussed. The problems of laboratory diagnosis of non
      O157 VTEC are considered and various laboratory methods are assessed. Evidence is
      presented that the particular E. coli serotypes now known to be VTEC were present
      in humans and animals many years ago, but have acquired the ability to produce VT
      and probably other virulence factors. Finally, predictions are made of the
      possible increase in problems associated with these emerging pathogens.

PMID- 10880179
TI  - Sources of Escherichia coli O157 and experiences over the past 15 years in
      Sheffield, UK.
AB  - In the first documented outbreak of HC caused by Escherichia coli O157, which
      occurred in the North-west USA in 1982, there was a strong association between
      infection and prior consumption of ground beef from a chain of fast food
      restaurants. Foods of bovine origin, including beef, milk and dairy products,
      have since been implicated in many outbreaks of infection world-wide.
      Investigations during the course of outbreaks, or at random, have shown that
      cattle are a major reservoir of E. coli O157. E. coli O157 was isolated from
      cattle at slaughter in Sheffield in 1987, this being the first isolation from
      cattle in the UK. Following a cluster of cases in May/June 1992, an abattoir
      study showed the organism to be present in 4% of cattle at slaughter and on up to
      a third of carcasses from rectal swab-positive animals. E. coli O157 was isolated
      from a food source (unpasteurized milk), for the first time in the UK, in
      Sheffield in May 1993. During surveillance in 1995-6, E. coli O157 was isolated
      from 15.7% of cattle, with a monthly prevalence which varied from 5 to 37%. E.
      coli O157 was also isolated from 2.2% of sheep. During surveillance in 1996, E.
      coli O157 was isolated from 5.9% of samples of lamb products and from 1.5% of
      samples of beef products, despite the prevalence in cattle being much higher than
      in sheep. Work is in progress to try to explain this higher prevalence in lamb
      products. During 1997 in Sheffield, the only cases of E. coli O157 for which a
      confirmed source was established were associated with direct animal contact on
      farm visits. During on-farm investigations of these cases, E. coli O157 was
      isolated from faecal samples from adult cattle, calves, three different breeds of
      sheep, two different breeds of pigs, goats and a pony.

PMID- 10880180
TI  - Survival of Escherichia coli in foods.
AB  - Studies describing the survival of Escherichia coli in foods, more often than not
      use the O157:H7 serovar as the target organism. Whilst E. coli O157:H7 is
      undoubtedly the predominant agent of concern for foodborne disease caused by
      enterohaemorrhagic E. coli (EHEC), a consequence of this concern is the commonly
      held view that this one serovar is 'atypical' in its response to stress
      conditions and therefore better able to survive adverse environments. Many of the
      studies published do not make comparisons with other E. coli (either commensal
      organisms or other pathogenic types) or other members of the Enterobacteriaceae,
      that would justify this view. Nevertheless, there has been a great deal of
      valuable data and information generated describing the fate of E. coli O157:H7 in
      a range of foods stored under various conditions. In many respects, the results
      of these studies are not surprising considering the survivability of other
      closely related pathogens, such as Shigella spp. This ability to survive in foods
      for long periods of time confirms the need for reliable control measures where
      contamination is possible or likely, e.g. proper handling and thorough cooking of
      beefburgers. The factors that may influence survival in different foods are
      described, with the intention of providing an insight in this area of food
      safety. Key considerations for carrying out survival studies are identified, with
      particular reference to methodologies used.

PMID- 10880181
TI  - Survival of verocytotoxigenic Escherichia coli O157 in soil, water and on
      surfaces.
AB  - Cattle and sheep are major reservoirs of Escherichia coli O157 and consequently
      these and certain other farm animals can pass out large numbers of this organism
      in their faeces. Thus the ability of the organism to survive in faeces, on
      pastureland and in associated water systems has important implications for its
      spread to crops by direct application of manure, by irrigation with infected
      water or directly to man by contact with animals or contaminated soil. Model
      systems were used to determine the persistence of the organism in river water,
      cattle faeces, soil cores and on stainless steel work surfaces. Survival of the
      organism was found to be greatest in soil cores containing rooted grass. Under
      these conditions viable numbers were shown to decline from approximately 10(8) g(
      1) soil to between 10(6) and 10(7) g(-1) soil after 130 d. When the organism was
      inoculated into cattle faeces it remained detectable at high levels for more than
      50 d. In contrast the organism survived much less readily in cattle slurry and
      river water where it fell in numbers from more than 10(6) ml(-1) to undetectable
      levels in 10 and 27 d, respectively. The survival of E. coli O157 was also
      investigated on stainless steel surfaces, where as air-dried deposits, it was
      shown to survive for periods in excess of 60 d. It was most stable at chill
      temperatures (4 degrees C) and viability was only partially reduced at 18 degrees
      C. In addition to stainless steel, the organism was shown to survive for extended
      periods on domestic (plastic) cutting boards, both at room and chill
      temperatures. Sanitizing agents, such as hypochlorites and a compound comprising
      both cationic and anionic-based active ingredients were found to be effective in
      killing various VTEC on stainless steel surfaces.

PMID- 10880182
TI  - Thermal inactivation of Escherichia coli O157:H7.
AB  - Verotoxin-producing Escherichia coli O157:H7 is a cause of serious foodborne
      illness. It has a very small infectious dose and so it is vital to eliminate this
      pathogen from food. As heat treatment is the method of bacterial destruction most
      frequently used in food processing, accurate prediction of thermal death rates is
      necessary to achieve desired safety margins whilst minimizing processing. In most
      studies thermal inactivation has been described using first-order reaction
      kinetics and D-values. Whilst this approach does not seem justified on a
      theoretical basis, and may increase inaccuracy, there is no doubt that it is
      convenient and in many cases provides an adequate description of thermal death. A
      review of published data on the measured thermal inactivation of E. coli O157:H7
      shows no strong evidence that a heat treatment of 70 degrees C for 2 min (or
      equivalent) fails to deliver a 6-decimal reduction in cell numbers.

PMID- 10880183
TI  - VTEC: lessons learned from British outbreaks.
AB  - Important Escherichia coli O157 outbreaks in England and Scotland since 1982-83
      are reviewed. The scientific lessons learned from them are described and their
      legal consequences outlined. The light shed by them on relationships between law
      and science is discussed, and questions of blame are analysed in the context of
      Reason's 'resident pathogen' metaphor and Vaughan's study of the 1986 Challenger
      Space Shuttle disaster.

PMID- 10880184
TI  - Molecular epidemiological investigation of enterohaemorrhagic Escherichia coli
      isolates in Japan.
AB  - We have established several measures for control and prevention of EHEC infection
      including designation of the disease as notifiable since there was the sudden
      increase in the incidence of infection with EHEC O157:H7 in Japan in 1996,
      involving multiple outbreaks. Improvements in methodologies for isolation of
      these organisms and enhanced laboratory screening have revealed a variety of
      sources in food and animals. Although there seems to be a bovine reservoir for
      O157 EHEC in Japan as well as North America and UK, different foods have been
      linked to EHEC infection including salads, radish sprouts and salmon roe. There
      is clear evidence that divergent clones of EHEC O157:H7 are prevalent throughout
      Japan based on laboratory surveillance, however, we still need to better define
      the role of EHEC serogroups other than Escherichia coli O157 as important causes
      of human infection.

PMID- 10880185
TI  - Escherichia coli: the best biological drinking water indicator for public health
      protection.
AB  - Public health protection requires an indicator of fecal pollution. It is not
      necessary to analyse drinking water for all pathogens. Escherichia coli is found
      in all mammal faeces at concentrations of 10 log 9(-1), but it does not multiply
      appreciably in the environment. In the 1890s, it was chosen as the biological
      indicator of water treatment safety. Because of method deficiencies, E. coli
      surrogates such as the 'fecal coliform' and total coliforms tests were developed
      and became part of drinking water regulations. With the advent of the Defined
      Substrate Technology in the late 1980s, it became possible to analyse drinking
      water directly for E. coli (and, simultaneously, total coliforms) inexpensively
      and simply. Accordingly, E. coli was re-inserted in the drinking water
      regulations. E. coli survives in drinking water for between 4 and 12 weeks,
      depending on environmental conditions (temperature, microflora, etc.). Bacteria
      and viruses are approximately equally oxidant-sensitive, but parasites are less
      so. Under the conditions in distribution systems, E. coli will be much more long
      lived. Therefore, under most circumstances it is possible to design a monitoring
      program that permits public health protection at a modest cost. Drinking water
      regulations currently require infrequent monitoring which may not adequately
      detect intermittent contamination events; however, it is cost-effective to
      markedly increase testing with E. coli to better protect the public's health.
      Comparison with other practical candidate fecal indicators shows that E. coli is
      far superior overall.

PMID- 10880186
TI  - The fate of Escherichia coli through water treatment and in distribution.
AB  - The removal of E. coli bacteria at each stage of water treatment is presented,
      showing how the filtration stages contribute most to reduction of bacterial
      numbers in the water. At treatment works without filtration stages, the emphasis
      is put on catchment management to limit contamination of the raw water and ensure
      that the numbers of viable E. coli in the source water remain low. Routine
      monitoring of the raw water provides data on seasonal trends in numbers of E.
      coli bacteria and allows effective management of supply. In the UK there is no
      evidence that E. coli grows in the water distribution system, whether in the
      planktonic stage or within biofilms (O'Neill et al. 1997). The detection of E.
      coli in the distribution system is rare and prompts a thorough investigation.
      Repeat samples are taken from the point which originally failed, along with a
      number of hydraulically linked samples including samples from hydrants. The
      response to the detection of E. coli is discussed. A series of experiments
      carried out on a pilot pipe system is briefly described and the results discussed
      in relation to the routine samples taken in the Thames Water Supply area.

PMID- 10880187
TI  - Waterborne Escherichia coli O157.
AB  - The waterborne route of Vero cytotoxin-producing E. coli (VTEC) O157 infection
      was first suggested in two unconnected human cases in 1985. Since then,
      waterborne VTEC O157 has been identified in sporadic cases and in outbreaks of
      illness. Recreational waters, private and municipal supplies have been implicated
      from microbiological, environmental and epidemiological studies of cases. In
      addition, a research cohort study of farm workers identified exposure to private
      water supplies as a risk factor for having antibodies to E. coli O157. Sources of
      contamination are thought to be animal and human faeces or sewage. The presence
      of low numbers of target organisms in water makes microbiological confirmation
      difficult, therefore epidemiological evidence has been essential in outbreak
      investigations. Despite the potential for contamination of water with VTEC O157,
      waterborne infection is relatively rare largely due to the susceptibility of the
      organism to water treatment processes. This paper presents the evidence for
      waterborne VTEC O157 infection, considering current microbiological,
      environmental and particularly epidemiological information.

PMID- 10880188
TI  - Methods for the detection and isolation of Shiga toxin-producing Escherichia
      coli.
AB  - Shiga toxin-producing Escherichia coli (STEC) are an important cause of
      haemorrhagic colitis and the diarrhoea-associated form of the haemolytic uraemic
      syndrome. Of the numerous serotypes of E. coli that have been shown to produce
      Shiga toxin (Stx), E. coli O157:H7 and E. coli O157:NM (non-motile) are most
      frequently implicated in human disease. Early recognition of STEC infections is
      critical for effective treatment of patients. Furthermore, rapid microbiological
      diagnosis of individual patients enables the prompt notification of outbreaks and
      implementation of control measures to prevent more cases. Most human infections
      caused by STEC have been acquired by the consumption of contaminated foods,
      especially those of bovine origin such as undercooked ground beef and
      unpasteurized cows' milk, and by person-to-person contacts. To identify the
      reservoirs of STEC and the routes of transmission to man, sensitive methods are
      needed as these pathogens may only be present in food, environmental and faecal
      samples in small numbers. In addition, sensitive and rapid detection methods are
      necessary for the food industry to ensure a safe supply of foods. Sensitive
      methods are also needed for surveillance programmes in risk assessment studies,
      and for studies on survival and growth of STEC strains. Cultural methods for the
      enrichment, isolation and confirmation of O157 STEC are still evolving. Several
      selective enrichment media have been described, of which modified tryptone soy
      broth with novobiocin and modified E. coli broth with novobiocin, seem to be the
      most appropriate. These media are minimally-selective broths that give a somewhat
      limited differential specificity favouring isolation of O157 STEC, as opposed to
      other Gram-negative bacteria, in the sample. An incubation temperature of 41-42
      degrees C further enhances selectivity. The occurrence of heat-, freeze-, acid-
      or salt-stressed STEC in foods means that it is important to be able to detect
      cells that are in a stressed state, as STEC generally have a very low infectious
      dose, and injured cells mostly retain their pathogenic properties. For the
      isolation of stressed O157 STEC, pre-enrichment in a non-selective broth is
      necessary. The most widely used plating medium for the isolation of typical
      sorbitol-non-fermenting strains of STEC of serogroup O157 is sorbitol MacConkey
      agar with cefixime and tellurite (CT-SMAC). As some STEC strains are sensitive
      for tellurite and/or are sorbitol-fermenting, the use of a second isolation
      medium, such as one of the newer chromogenic media, is recommended.
      Immunomagnetic separation (IMS) following selective enrichment, and subsequent
      spread-plating of the concentrated target cells onto CT-SMAC agar, appears to be
      the most sensitive and cost-effective method for the isolation of E. coli O157
      from raw foods. IMS increases sensitivity by concentrating E. coli O157 relative
      to background microflora, which may overgrow or mimic O157 STEC cells on
      selective agars. While cultural isolation of O157 STEC from foods and faeces is
      time-consuming, labour-intensive and hence, costly, rapid immunological detection
      systems have been developed which significantly reduce the analysis time. These
      methods include enzyme-linked immunosorbent assays (ELISAs), colony immunoblot
      assays, direct immunofluorescent filter techniques, and several immunocapture
      techniques. Both polyclonal and monoclonal antibodies specific for the O and H
      antigens are used for these methods. Many of these test systems are able to
      detect less than one O157 STEC cell g(-1) of raw meat after overnight enrichment.
      Presumptive results are available after just one day, but need to be completed
      with the isolation of the organisms. The primary use of these procedures is
      therefore to identify food and faecal samples that possibly contain O157 STEC.

PMID- 10880189
TI  - Food safety through the meat supply chain.
AB  - Food poisoning in humans can be caused by many different bacterial genera. While
      the incidence of food poisoning in England, Wales and Scotland from Salmonella
      has reached a plateau, there has been an increase in the incidence from
      Campylobacter. The incidence from Escherichia coli O157:H7 rose to 1997 but
      declined slightly in 1998 (data from the Public Health Laboratory Service and the
      Scottish Centre for Infection and Environmental Health). This organism has a high
      virulence in humans and a very low infective dose. Infection can produce a wide
      range of responses, including death. The low infective dose presents a major
      threat. The organism is relatively heat-sensitive and the cooking of food
      products to achieve a centre core temperature of 70 degrees C for 2 min is
      sufficient to destroy it. It is relatively acid-tolerant and will survive for
      several weeks at pH 4.2. Several foodstuffs, as well as water, have been
      implicated in world-wide outbreaks. The E. coli O157:H7 food-borne outbreak in
      Lanarkshire in 1996 led to 21 fatalities. The Pennington Group report, issued in
      April 1997, reported on the circumstances leading to this outbreak, the
      implications for food safety and the lessons to be learnt. Four areas covered
      within the Pennington Group report specific to meat hygiene are reviewed in this
      paper. On-farm practices must ensure the presentation of clean animals for
      slaughter. There is a requirement for the development and introduction of risk
      assessment techniques based upon Hazard Analysis of Critical Control Points in
      abattoirs, and the Meat and Livestock Commission (MLC) is producing a manual for
      use by the abattoir sector. The Pennington report stated that there was a need
      for research into the potential use of end-process treatments such as steam
      pasteurization. The MLC is involved in evaluating such a system. Meat production
      premises and butchers' shops in England are introducing HACCP through an MLC
      scheme funded by the Department of Health. At the point of consumption, food
      safety is improved by the provision of practical guidelines regarding the
      handling of meat and meat products. These are distributed at retail outlets and
      communicated to secondary schools via MLC's educational publications.

PMID- 10880190
TI  - The fate of Escherichia coli and E. coli O157 in cattle slurry after application
      to land.
AB  - The fate of both faecal Escherichia coli and E. coli O157 in slurry following
      application to arable and grass plots on a clay loam soil was studied. Slurry (5%
      dry matter) containing 5.3 x 10(4) ml(-1) E. coli and 30 E. coli O157 100 ml(-1)
      was spread in early March. Initially, almost all E. coli were retained in the
      upper layers of the soil. Escherichia coli numbers steadily declined to less than
      1% of those applied by day 29, and E. coli O157 were only detected in the soil
      and on the grass for the first week after application. There was some transport
      of bacteria to deeper layers of the soil, but this was approximately 2% of the
      total; transport to drains over the same period was mainly associated with
      rainfall events and amounted to approximately 7% of applied E. coli. However,
      there were indications that periods of heavy rainfall could cause significant
      losses of E. coli by both leaching and run-off. Experimental studies showed that
      E. coli O157 on grass, which was subsequently ensiled in conditions allowing
      aerobic spoilage, could multiply to numbers exceeding 10(6) g(-1) in the silage.

PMID- 10880191
TI  - The potential for the control of Escherichia coli O157 in farm animals.
AB  - The presence of Escherichia coli O157 in the faeces of farm animals appears to
      provide a primary route for human infection, either through physical contact or
      by contamination of the food chain. Controlling the survival and proliferation of
      this pathogen in the ruminant gut could offer a measure of protection in the
      short term, and ultimately complement alternative biotechnological based
      solutions. Normally, E. coli is greatly outnumbered in the ruminant gut by
      anaerobic bacteria, producers of weak acids inhibitory to the growth of this
      species. Withdrawal of feed prior to animal slaughter reduces the concentration
      of these acids in the gut and may be accompanied by the proliferation of E. coli.
      There are conflicting reports concerning the effects of changes in the ruminant
      diet upon faecal shedding of E. coli O157. It is contended that it is important
      to identify animal husbandry methods or feed additives that may be accompanied by
      an increased risk of proliferation of this pathogen. Greater understanding of the
      mechanisms involved in bacterial survival in the presence of weak acids, in the
      interactions between E. coli and other gut bacteria, and of the effects of some
      antibacterial plant secondary plant compounds on E. coli, could lead to the
      development of novel control methods.

PMID- 10880192
TI  - A novel stereocontrolled synthesis of 1,2-trans cyclopropyl ketones via suzuki
      type coupling of acid chlorides with cyclopropylboronic acids.
AB  - [reaction: see text] The palladium-catalyzed cross-coupling reaction of
      cyclopropylboronic acids with acyl chlorides was achieved by the combination of
      Ag(2)O and K(2)CO(3) as the base. Highly enantiomerically enriched cyclopropyl
      ketones (ee >90%) were also obtained by the reaction of corresponding chiral
      cyclopropylboronic acids.

PMID- 10880193
TI  - Synthesis and conformation of Gly-Gly dipeptides constrained with phenylalanine
      like aminocaproic acid linkers.
AB  - [structure: see text] The constraint of dipeptides with linkers derived from 6
      aminocaproic acid (Aca) is a useful means of constructing a beta-turn
      peptidomimetic. The extension of this concept to the mimicry of a tripeptide
      entails the incorporation of a side chain moiety on either end of the Aca chain.
      The synthesis and conformational analysis of two exemplary compounds is
      discussed.

PMID- 10880194
TI  - Synthesis of alpha-amino-alpha'-diazomethyl ketones via ring opening of
      substituted cyclopropanones with alkyl azides. A facile route to N-substituted 3
      azetidinones.
AB  - [reaction: see text] The reaction of alkyl azides with triethyl(1-methoxy-2, 2
      dimethyl-cyclopropoxy)silane affords a series of alpha-amino-alpha'-diazomethyl
      ketones in moderate yields (38-54%). The mechanism of this novel process is
      discussed. The diazomethyl ketones could also be cyclized to the corresponding N
      substituted 3-azetidinones in good yield upon treatment with Rh(2)(OAc)(4).

PMID- 10880195
TI  - Synthesis of enantiopure 1-azabicyclo[3.2.2]nonanes via stereoselective capture
      of chiral carbocations.
AB  - [reaction: see text] A new class of doubly functionalized and enantiomerically
      pure 1-azabicyclo[3.2.2]nonanes derived from quincorine and quincoridine is
      described. 2,5-Disubstituted quinuclidines with a C9-mesyloxy group were easily
      transformed into the corresponding halides upon treatment with lithium salts.
      Subsequent silver salt-mediated ring expansion stereoselectively furnished the
      title azabicyclics. Chiral carbocations which are configurationally stable and
      nonplanar are postulated to account for the striking stereoselectivity of the
      capture of external nucleophile. 5-Ethynyl-2-iodomethylquinuclidines afford the
      alpha-benzoyloxy amines rather than alpha-methoxy amines, even in MeOH.

PMID- 10880196
TI  - Guest and subunit exchange in self-assembled ionophores.
AB  - [reaction: see text] Self-assembled ionophores, formed by hydrogen bonding of
      isoG 1 around a cation, are dynamic structures. Multinuclear NMR spectroscopy in
      CD(3)CN-CDCl(3) showed that cation exchange is >10(4) faster than exchange of
      isoG 1 ligand in (isoG 1)(10)-Cs(+) Ph(4)B(-). The cationic guest also affected
      the kinetic stability of the complex. 2D-EXSY NMR experiments in CDCl(3) showed
      that ligand exchange was 2 orders of magnitude faster for the Li(+)-decamer than
      for the Cs(+)-decamer.

PMID- 10880197
TI  - Efficient synthesis of the C(1)-C(11) fragment of the tedanolides. The nonaldol
      aldol process in synthesis.
AB  - [reaction: see text] The nonaldol aldol process developed in our laboratories has
      been applied to the synthesis of a C(1)-C(11) fragment 22 of the novel
      macrocyclic cytotoxic agents tedanolide and 13-deoxytedanolide 1 and 2. The
      commercially available hydroxy ester 7 was converted in 24 steps into compound 22
      using two nonaldol aldol reactions.

PMID- 10880198
TI  - [4 + 1] cycloaddition of bis(alkylthio)carbenes with vinyl isocyanates. Total
      synthesis of (+/-)-mesembrine.
AB  - [reaction: see text] The Sceletium alkaloid mesembrine has been synthesized in
      13% overall yield by a sequence featuring a [4 + 1] cycloaddition of a
      bis(alkylthio)carbene with a functionalized vinyl isocyanate.

PMID- 10880199
TI  - Rhodium-catalyzed asymmetric ring opening of oxabicyclic alkenes with phenols
AB  - The scope of the rhodium-catalyzed asymmetric ring opening reaction of
      oxabenzonorbornadiene has been extended to include phenolic nucleophiles. The
      enanatioenriched, functionalized dihydronaphthalene products are highly valuable
      intermediates for which no other practical methods of preparation are available.
      A new catalyst system has been developed which allows the use of less reactive o
      halophenols. The utility of these products has been demonstrated through their
      application in the synthesis of benzofuran polycyclic materials.

PMID- 10880200
TI  - Selective N-debenzylation of benzylamino derivatives of 1, 6-anhydro-beta-D
      hexopyranoses
AB  - When the series of 2-, 3-, and 4-(benzylamino)-2-, 3-, and 4-deoxy derivatives of
      1,6-anhydro-beta-D-hexopyranoses in the D-gluco, D-lyxo, and D-arabino
      configurations were reacted with diisopropyl azodicarboxylate, N-benzyl groups
      were selectively cleaved in the presence of O-benzyl groups. The yields ranged
      from 51 to 97%. The debenzylation of some aliphatic benzylamines is also
      discussed.

PMID- 10880201
TI  - The C-ring problem of sterol biosynthesis: TiCl(4)-induced rearrangement into the
      anti-Markovnikov cation corresponding to the C-ring.
AB  - [reaction: see text] Cation 9, generated by the reaction of diol 8 and
      BF(3).Et(2)O, SnCl(4), Sc(OTf)(3), FeCl(3), TiF(4), or CF(3)SO(3)H, leads to a
      hydride shift, providing cation 11, which corresponds to the initiation of
      backbone rearrangement. On the other hand, TiCl(4) selectively induces
      rearrangement to secondary cation 13 by ring expansion, which corresponds to the
      C-ring formation of sterol biosynthesis. AlCl(3) and ZrCl(4) induce further
      rearrangement into six-membered ring tert-cation 16.

PMID- 10880202
TI  - First example of memory of chirality in carbenium ion chemistry
AB  - The non-Kolbe reaction of N-benzoyloxazolidine derivatives 6 derived from L
      serine gave optically active N,O-acetals 7 when graphite was used as an anode
      material. This reaction represents the first example of "memory of chirality" in
      carbenium ion chemistry. The material used for the anode was critical for the
      memory of chirality. The substitution of carboxyl group with methoxyl group was
      found to proceed with an inversion mechanism.

PMID- 10880203
TI  - Synthesis of aminoglycoside-modified oligonucleotides.
AB  - [structure: see text] To study the structural requirements of aminoglycoside
      binding to nucleic acids, compound 1-an analogue of the naturally occurring
      nucleoside J-was synthesized. When incorporated into oligodeoxynucleotides, 1
      leads to thermal stabilization of the resulting duplexes. The increase in pairing
      affinity is stronger with complementary RNA than with DNA.

PMID- 10880204
TI  - Solid-phase synthesis of cyclic peptide-DNA hybrids.
AB  - [reaction: see text] A methodology for preparing cyclic peptide-DNA hybrids on
      controlled pore glass in high yield is reported. This methodology employs
      Fmoc/Alloc-protected amino acid and nucleoside phosphoramidites on an omega
      hydroxylauric acid-derivatized support and is suitable for library synthesis. A
      cyclic hybrid of the sequence Glu-Leu-TT-DP-Lys, where Glu and Lys are linked and
      T denotes a 5'-amino-5'-deoxynucleotide, exhibited high resistance to exo- and
      endonucleases.

PMID- 10880205
TI  - 3-Bromopentadienylsilane: A new reagent for the introduction of a functional
      pentadienyl unit with fixed configuration
AB  - The (Z)-1-trimethylsilyl-3-bromopenta-2,4-diene 3 was prepared through a sequence
      involving the reductive silylation of butadiene, dibromocarbene addition on the
      resulting disilane 1, and thermolytic ring opening. With aldehydes, this new
      pentadienylsilane reacts exclusively via an S(E)' ' pathway. In the presence of
      an alcohol or a carbamate under Lewis acid activation, 3 yields, respectively,
      bromopentadienyl ethers or bromopentadienyl-protected amines.

PMID- 10880206
TI  - Solution-phase synthesis of diaryl selenides using polymer-supported borohydride.
AB  - [reaction: see text] A new series of selenium-containing diaryl retinoids have
      been prepared by a new direct nickel(II)-catalyzed coupling of a diselenide with
      an iodoaryl in the presence of polymer-supported borohydride.

PMID- 10880208
TI  - Water/MAO acceleration of the zirconocene-catalyzed asymmetric methylalumination
      of alpha-olefins
AB  - The zirconocene-catalyzed enantioselective methylalumination of terminal alkenes
      is greatly accelerated in the presence of water. Terminal olefins that are inert
      under the standard conditions can be readily methylated in good yields and with
      good to high enantioselectivities. Furthermore, methylaluminoxane is also shown
      to accelerate the reaction, albeit at a lesser rate.

PMID- 10880207
TI  - alpha,beta-epoxy vinyl triflates in Pd-catalyzed reactions.
AB  - [reaction: see text] Reactions of steroidal alpha,beta-epoxy vinyl triflates in
      Pd-catalyzed reactions are described. Oxidative insertion of Pd(0) into the C-O
      bond, giving vinylpalladium 12, is faster than formation of the pi-allyl
      derivative from the vinyl epoxide. Although 12 can be trapped under certain
      conditions, it eventually rearranges to palladium alkoxide 14, which is in
      equilibrium with 15 and/or 10.

PMID- 10880210
TI  - Protein surface recognition by synthetic receptors based on a
      tetraphenylporphyrin scaffold.
AB  - [structure: see text] Receptors based on a tetraphenylporphyrin scaffold bearing
      different charged and hydrophobic groups have been synthesized. The interactions
      of these with horse heart cytochrome c were studied by fluorescence spectroscopy.
      Receptor 4 was identified to be the strongest synthetic receptor (K(d) = 20 nM)
      for cytochrome c. The differences in affinity among the receptors reflected a
      dependence on the number of anionic and hydrophobic groups.

PMID- 10880209
TI  - Baeyer-Villiger oxidation promoted by reaction of peracids with cyclic
      oxocarbenium ions generated in situ from internal hemiketals.
AB  - [reaction: see text] Reactive cyclic oxocarbenium ions, generated in situ from
      internal hemiketals, undergo Baeyer-Villiger oxidation upon exposure to m
      chloroperbenzoic acid leading, after hydrolysis of the resultant lactones, to
      acyclic fragments for use in natural product synthesis.

PMID- 10880211
TI  - A molecular NAND gate based on Watson-Crick base pairing.
AB  - [reaction: see text] A DNA-binding dye, 4',6-diamidino-2-phenylindole (DAPI)
      signals AT base pairing with a shift in the fluorescence emission spectrum. The
      signaling follows W-C base-pairing rules, and both dAMP and dTMP are required for
      the largest spectral shift. Thus, the dye with its two phosphate receptor sites
      functions as a molecular NAND gate accepting nucleotides as inputs. Moreover,
      when the observation wavelength is changed from 470 to 411.5 nm, the gate
      functions in TRANSFER logic.

PMID- 10880212
TI  - Pd(PhCN)(2)Cl(2)/P(t-Bu)(3): a versatile catalyst for Sonogashira reactions of
      aryl bromides at room temperature.
AB  - [reaction: see text] Pd(PhCN)(2)Cl(2)/P(t-Bu)(3) serves as an efficient and a
      versatile catalyst for room-temperature Sonogashira reactions of aryl bromides.

PMID- 10880213
TI  - Stereoselective inhibition of alpha-L-fucosidases by N-benzyl
      aminocyclopentitols.
AB  - [structure: see text] (1R,2R,3R,4R,5R)-4-Amino-5-methylcyclopentane-1,2,3 -tr iol
      8, its 4S stereoisomer 9, and their acyclic analogues (R)- and (S)-2-aminobutanol
      11 and 12 are selective but moderate inhibitors of alpha-L-fucosidases. N
      Benzylation selectively enhances inhibition potency for aminocyclopentitol 8 (-->
      1, K(i) = 6.8 x 10(-)(7) M) but decreases inhibition for its 4S-stereoisomer 9 (-
      > 2, K(i) = 1.1 x 10(-)(4) M) and for the aminobutanols 11 (--> 13, no
      inhibition) and 12 (--> 14, no inhibition).

PMID- 10880214
TI  - A poly(ethylene glycol)-supported quaternary ammonium salt: An efficient,
      recoverable, and recyclable phase-transfer catalyst
AB  - A quaternary ammonium salt readily immobilized on a soluble poly(ethylene glycol)
      polymer support efficiently catalyzes different reactions carried out under phase
      transfer catalysis conditions; the catalyst, easily recovered by precipitation
      and filtration, shows no appreciable loss of activity when recycled three times.

PMID- 10880215
TI  - Phosphatase-triggered guest release from a cyclodextrin complex.
AB  - [reaction: see text] A synthetic supramolecular system is described that models
      the effect of phosphoryl transfer in molecular recognition. beta-Cyclodextrin-6A
      phosphate (pCD), which is shown to be a substrate of alkaline phosphatase, binds
      cationic aromatic guests, including anticancer agents, up to 100-fold better than
      native beta-CD. The above observations demonstrate that pCD is capable of
      releasing the guests from its cavity upon hydrolysis with the phosphatase, as
      also confirmed by monitoring the hydrolysis in the presence of a guest.

PMID- 10880216
TI  - A survey of acid catalysts for use in two-step, one-flask syntheses of meso
      substituted porphyrinic macrocycles.
AB  - [reaction: see text] Diverse Lewis acids and Bronsted acids were examined in the
      two-step, one-flask synthesis of meso-tetraphenylporphyrin, N-confused
      tetraphenylporphyrin, and tetraphenylsapphyrin. The scope of acid catalysis was
      found to be very broad, with 35 of 45 acids providing TPP in yields ranging from
      5% to 58%. NC-TPP was also widely observed in yields of 1-40%, and TPS was
      infrequently observed in yields of <1%. Additionally, conditions were found for
      direct preparation of magnesium TPP and copper TPP.

PMID- 10880217
TI  - General asymmetric hydrogenation of hetero-aromatic ketones
AB  - trans-RuCl(2)[(R)-xylbinap][(R)-daipen] or the S,S complex acts as an efficient
      catalyst for asymmetric hydrogenation of hetero-aromatic ketones. The
      hydrogenation proceeds with a substrate-to-catalyst molar ratio of 1000-40000 to
      give chiral alcohols in high ee and high yield. The enantioselectivity appears to
      be little affected by the properties of the hetero-aromatic ring. This method
      allows for asymmetric synthesis of duloxetine, an inhibitor of serotonin and
      norepinephrine uptake carriers.

PMID- 10880218
TI  - Diastereoselective formation of 5-vinylcyclopentenes from 1, 6-enynes: cobalt
      mediated C-H allylic activation and formal 5-endo-Dig cyclization
AB  - A novel intramolecular cyclization reaction mediated by dicobalt octacarbonyl
      (Co(2)(CO)(8)) is reported. Thermolysis in an argon atmosphere transforms the
      cobalt complex of 1-trimethylsilyl-6-hepten-1-ynes into 1-trimethylsilyl-5
      vinylcyclopentenes in good yield and in a highly diastereoselective manner. This
      formal 5-endo-dig cyclization is proposed to proceed via an allylic C-H oxidative
      addition.

PMID- 10880219
TI  - Electronic control of the Bergman cycloaromatization: synthesis and chemistry of
      chloroenediynes.
AB  - [reaction: see text] A series of cyclic mono- and dichloroenediynes have been
      prepared using an intramolecular carbenoid coupling reaction. The halogen atom
      had a retardative effect on Bergman cycloaromatization in every case examined,
      and atom transfer chemistry was demonstrated, resulting in formation of adducts.

PMID- 10880220
TI  - A regioselective Ru-catalyzed alkene-alkyne coupling.
AB  - [reaction: see text] The reaction of silylalkynes and terminal alkenes proceeds
      with complete control of regioselectivity by the silyl substituent to give
      geometrically defined vinylsilanes. Since terminal alkynes normally give
      mixtures, protodesilylation of these adducts then constitutes a regioselective
      addition of terminal alkynes to terminal alkenes.

PMID- 10880221
TI  - Regiospecific carbonylative annulation of iodophenol acetates and acetylenes to
      construct the flavones by a new catalyst of palladium-thiourea-dppp complex.
AB  - [reaction: see text] Regiospecific carbonylative annulation of o-iodophenol
      acetates and acetylenes mediated by palladium-thiourea-dppp complex in the
      presence of base at 40 degrees C under a balloon pressure of CO generates
      diversified flavones in high yields. This newly developed synthetic technology
      provides a highly efficient method for potential application to the combinatorial
      synthesis of those heterocycles on the solid support.

PMID- 10880222
TI  - Diastereotopic differentiation on phosphorus templates via the ring-closing
      metathesis reaction.
AB  - [reaction: see text] A strategy is described in which the ring-closing metathesis
      reaction is utilized to desymmetrize a number of pseudo-C(2)-symmetric phosphorus
      templates 1-3. These reactions give excellent levels of selectivity (12-15:1)
      with vinyl phosphonamides containing a (E)-Ph group on the diastereotopic
      olefins. This approach is being developed as an effective method of obtaining P
      chiral phosphonamides and phosphonates.

PMID- 10880223
TI  - Formation of aromatic rings through enamine annulation
AB  - Condensation of pyrrolidine enamine of ketones with 1, 4-diacetoxy-2-butanone
      provides a new, concise synthetic route to substituted benzenes, dihydroindenes,
      tetrahydronaphthalenes, and di- and octahydrophenanthrenes. The reaction produced
      modest yields with regiocontrol of the secondary amine substituent.

PMID- 10880224
TI  - A new approach to macrocyclization via alkene formation in catalytic diazo
      decomposition. Synthesis of patulolides A and B.
AB  - [reaction: see text] Effective synthetic uses of bisdiazocarbonyl compounds for
      the selective construction of diverse macrocycles, including the synthesis of
      patulolides A and B, by catalytic "carbene dimer" formation are reported. Control
      of stereochemistry and efficient methods for product isomerization or kinetic
      isomer differentiation have been achieved.

PMID- 10880226
TI  - Rate constant for the ring opening of the 2, 2-difluorocyclopropylcarbinyl
      radical

PMID- 10880225
TI  - A polymer-supported rhodium catalyst that functions in polar protic solvents
AB  - Highly cross-linked macroporous polymers are excellent supports for
      heterogenizing rhodium alkene hydrogenation and hydroboration catalysts. The
      permanent pore structure of the support enables high conversions and excellent
      yields with minimal workup (filtering). These heterogenized catalysts can be
      reused, and due to the permanent pore structure, they function in a broad range
      of solvents including polar protic. Control experiments reveal that catalysis
      occurs exclusively within the polymer matrix, and not due to leached catalyst.

PMID- 10880227
TI  - Cloning and functional characterization of a novel c-mpl variant expressed in
      human CD34 cells and platelets.
AB  - The thrombopoietin receptor, c-mpl, is a crucial element not only in
      thrombopoietin (TPO)-initiated signaling pathways but also in the regulation of
      the circulating amount of TPO. We have identified a new c-mpl isoform, called c
      mpl-del, that lacks 72 bp (24 amino acids) in the extracellular region of c-mpl
      and arises as a consequence of alternative RNA splicing between exons 8 and 9. c
      mpl-del is expressed along with c-mpl-wt in blood mononuclear cells,
      CD34(+)cells, megakaryocytes, and platelets prepared from either normal donors or
      ET patients, although its relative expression appears to increase with
      megakaryocyte differentiation. The c-mpl-del-transfected cells expressed greater
      amounts of c-mpl-del RNA and protein than the comparable c-mpl-wt-transfected
      cells, however flow cytometry analysis could not detect any c-mpl receptor on the
      surface of the c-mpl-del-transfected cells. Further evidence for the absence of
      surface c-mpl-del was that in contrast to cells transfected with c-mpl-wt, those
      transfected with c-mpl-del did not grow in response to TPO, failed to undergo
      tyrosine phosphorylation of TPO-specific signal molecules, and did not bind(125)I
      rHuTPO. Taken together, these results demonstrate that c-mpl-del, a naturally
      occurring variant of c-mpl, fails to be incorporated into the cell membrane but
      might serve as a mechanism to decrease the overall expression of functional c-mpl
      late in megakaryocyte differentiation.

PMID- 10880228
TI  - Subtraction cloning and initial characterization of novel epo-immediate response
      genes.
AB  - Recent studies of erythropoietin (Epo) receptor signalling suggest that signals
      for mitogenesis, survival and differentiation are relayed efficiently by receptor
      forms lacking at least seven of eight cytoplasmic (phospho)tyrosine [(P)Y] sites
      for effector recruitment. While such receptor forms are known to activate Jak2
      and a limited set of known immediate response genes (IRGs), the complex
      activities they exert predict the existence of additional target genes. To
      identify such targets, a minimal Epo receptor chimera was expressed in Epo
      responsive erythroid SKT6 cells, and genes whose transcription is induced via
      this active receptor form were cloned by subtractive hybridization. Several known
      genes not previously linked to Epo signalling were discovered to be Epo IRGs
      including two which may further propagate Epo signals [Prl1 tyrosine phosphatase
      and receptor activator of of NFkappaB (Rank)], and three regulators of protein
      synthesis (EF1alpha, eIF3-p66 and Nat1). Several Epo IRGs were novel murine
      clones including FM2 and FM6 which proved to represent broadly expressed IRGs,
      and FM3 and FL10 which were induced primarily in haematopoietic cells.
      Interestingly, FL10 proved to correspond to a recently discovered regulator of
      yeast mating-type switching, and was induced by Epo in vivo. Thus, several new
      Epo signalling targets are described, which may modulate haematopoietic cell
      development.

PMID- 10880229
TI  - Molecular cloning of the guinea-pig IL-5 receptor alpha and beta subunits and
      reconstitution of a high affinity receptor.
AB  - The functional IL-5 receptor is a heteromeric complex consisting of an alpha and
      beta subunit. The cloning, sequencing and expression of guinea-pig IL-5Ralpha and
      beta subunits is described. The guinea-pig IL-5Ralpha subunit cDNA encodes a
      protein of M(r)47 kDa, which is 72 and 66% homologous to the human and murine
      orthologs, respectively. Three guinea-pig IL-5Rbeta subunit cDNA clones were
      isolated, which differ in the N-terminus and are 56-64% homologous to the human
      and murine IL-5Rbeta subunits. Expressing human IL-5Ralphabeta and guinea-pig IL
      5Ralphabeta(1)in the baculovirus-insect cell system resulted in recombinant
      receptors which bound hIL-5 with high affinity (K(d)=0.19 and 0.11 nM,
      respectively). Expressing just gpIL-5Ralpha was not sufficient to demonstrate
      binding. This contrasts with the human receptor, where hIL-5Ralpha alone can bind
      hIL-5 with high affinity. gpIL-5Ralphabeta(1)bound both hIL-5 and mIL-5 with
      comparable affinity (K(i)=0.10 and 0.06 nM), similar to that seen with hIL
      5Ralphabeta. Thus, both the heteromeric hIL-5R and gpIL-5Ralphabeta(1)can bind
      multiple IL-5 orthologs with high affinity whereas the murine IL-5R is selective
      for the murine ligand.

PMID- 10880230
TI  - Identification of regions within the third FnIII-like domain of the IL-5Ralpha
      involved in IL-5 interaction.
AB  - Previously, two binding sites for interleukin 5 (IL-5) were identified on the IL
      5 receptor alpha chain (IL-5Ralpha). They are located within the CD loop of the
      first fibronectin type III (FnIII)-like domain and the EF loop of the second
      FnIII-like domain. The first binding site was identified by exploiting the
      different abilities of human IL-5Ralpha (hIL-5Ralpha) and mouse IL-5Ralpha (mIL
      5Ralpha) to bind hIL-5. Here we show that ovine IL-5 (oIL-5) has the ability to
      activate the hIL-5Ralpha but not the mIL-5Ralpha. By using chimeras of the mIL
      5Ralpha and hIL-5Ralpha we demonstrate that residues within the first and third
      FnIII-like domains of mIL-5Ralpha are responsible for this lack of activity.
      Furthermore, mutation of residues on hIL-5Ralpha to mIL-5Ralpha within the
      predicted DE and FG loop regions of the third FnIII domain reduces oIL-5
      activity. These results show that regions of the third FnIII domain of IL-5Ralpha
      are involved in binding, in addition to the regions in domains one and two of the
      IL-5Ralpha that were identified in an earlier study.

PMID- 10880231
TI  - p38 map kinase regulates TNF-alpha production in human astrocytes and microglia
      by multiple mechanisms.
AB  - In the vertebrate central nervous system (CNS), tumour necrosis factor-alpha (TNF
      alpha) is produced by astrocytes and microglia and mediates cell injury in nerve
      cells and oligodendrocytes. In the present study, we have used a specific
      inhibitor of p38 MAP kinase, SB203580 to examine the role of p38 MAP kinase in
      regulation of TNF-alpha production in human astrocytes and microglia in terms of
      levels of mRNA and secreted protein. A reverse transcriptase polymerase chain
      reaction (RT-PCR) analysis showed that increased levels of TNF-alpha mRNA were
      induced in astrocytes by IL-1beta treatment, and in microglia by bacterial
      lipopolysaccharide (LPS). In microglia, treatment with SB203580 reduced the level
      of TNF-alpha mRNA, but in astrocytes it did not. However, the secretion of TNF
      alpha by both astrocytes and microglia was markedly inhibited by SB203580 at a
      low concentration. TNF-alpha secretion was reduced approximately 80% in
      astrocytes and 85% in microglia. The results demonstrate a key role played by p38
      MAP kinase in upregulation of TNF-alpha mRNA levels in LPS-activated human
      microglia, whereas p38 MAP kinase is involved in post-transcriptional regulation
      of TNF-alpha production at translational level in IL-1beta-activated human
      astrocytes.

PMID- 10880232
TI  - Induction of oxidative DNA damage in u937 cells by TNF or anti-Fas stimulation.
AB  - TNF and Fas signaling pathways are reported to induce mitochondrial damage
      associated with production of oxygen radicals. We examined whether such radical
      production elicited detectable nuclear DNA damage in U937 cells following
      treatment with TNF or with anti-Fas antibodies. Using GC-mass spectroscopy for
      analysing base oxidation, several oxidized species increased significantly
      following TNF treatment, whereas anti-Fas resulted in less detectable oxidative
      damage using this assay. Cytogenetic analysis showed that, in the presence of
      aphidicolin, which blocks several types of DNA repair, TNF induced extensive
      chromosomal damage. Aphidicolin also synergized with TNF and anti-Fas in inducing
      cell death which was prevented by reducing atmospheric oxygen or addition of n 
      acetyl cysteine, a scavenger of oxygen radicals. Thus, several lines of evidence
      point to the TNF and Fas pathways inducing extensive oxidative DNA damage and
      repair, and suggest potential roles for these pathways in mutagenesis and aging.

PMID- 10880233
TI  - Role of STAT3 and C/EBP in cytokine-dependent expression of the mouse serum
      amyloid P-component (SAP) and C-reactive protein (CRP) genes.
AB  - Inflammation is accompanied by a rapid increase in blood levels of acute phase
      proteins synthesized by hepatocytes in response to cytokines. Although C-reactive
      protein (CRP) levels increase dramatically in most mammals, the major acute phase
      protein in the mouse is the homologous pentraxin, serum amyloid P-component
      (SAP), whereas CRP is a minor acute phase reactant. The molecular basis for the
      pronounced difference in SAP and CRP gene expression in the mouse is unknown.
      Transfection of ++/Li mouse hepatoma cells with CAT-reporter constructs
      containing the 5'-flanking region of the mouse CRP gene indicated that
      transcription was stimulated by either IL-6, or IL-6 plus IL-1, when > or =360 bp
      of the 5'-proximal DNA was present. Examination of the 5'-flanking region of the
      mouse SAP gene revealed that the region between -433 and -397 from the
      transcription start site responded to IL-1 and IL-6 by binding both STAT3 and
      C/EBPbeta. This responsive region consisted of two adjacent C/EBPbeta consensus
      sites that overlap with two STAT3 consensus sites and was found to bind C/EBPbeta
      at an upstream site of -427 to -409 and STAT3 at a downstream site of -415 to 
      397. By contrast, the 360 bp promoter of the CRP gene was bound only by STAT3 at
      consensus sites at -93, -142, -173, and -287 from the start site; however, a
      single consensus site for C/EBP at -75 was not recognized. STAT3 appears to be
      necessary for both mouse SAP and CRP gene transcription since overexpression of
      an inactive, deletion mutant of STAT3 inhibited transcription of both genes. The
      results indicate that both STAT3 and C/EBPbeta participate in mouse SAP gene
      expression, whereas only STAT3 is involved in mouse CRP gene expression. The
      findings for mouse SAP gene expression are consistent with the reported
      interaction between these two transcription factors for human CRP gene
      transcription.

PMID- 10880234
TI  - Regulation of interleukin 12 and interleukin 10 expression in vaccinia virus
      infected human monocytes and U-937 cell line.
AB  - Regulation of IL-12 and IL-10 production in normal human monocytes infected with
      vaccinia virus (VV) was analysed. IL-12 and IL-10 mRNAs were measured by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and IL-12 and IL-10 protein by
      ELISA. RT-PCR analysis revealed a marked-up regulation of IL-12 (p40) and IL-10
      expression in virally infected cells compared with that from control (non
      infected) cells at 24 h post-infection (p.i.). IL-12 transcripts occurred earlier
      (at 4 h p.i.) than IL-10 mRNA. A significant increase in IL-12 and IL-10
      secretion into the medium was caused by the virus, and even a much more
      pronounced increase in both interleukins expression (mRNAs and proteins) followed
      LPS or Staphylococcus aureus treatment. Vaccinia virus infection did not alter IL
      10 secretion and IL-10 mRNA content (or even cause a decrease) in a human
      monocytic cell line U937. Undetectable levels of IL-12 protein were found in the
      cell line although the transcripts were present in the cells at first hours p.i.
      It appears now that vaccinia virus transiently and sequentially induces IL-12 and
      IL-10 in human monocytes.

PMID- 10880235
TI  - Monocyte migration inhibitory factor synthesis and gene expression in particle
      activated macrophages.
AB  - This study analysed MIF mRNA and protein expression in human macrophages exposed
      in vitro to polymethylmethacryate and titanium alloy particles. MIF levels
      released from macrophages without exposure to particles were in the range of 2-4
      ng/ml. Exposure of macrophages to particles as demonstrated increased MIF release
      at 0. 075%-0.225% v/v particle concentration, which was maximal at 12-24 h. MIF
      mRNA signal levels in cells with and without particles at a concentration of
      0.075% showed no significant differences in a time course experiment. The profile
      of MIF release in response to increasing particle concentration coincided with
      increased release of lactate dehydrogenase. The viability of the cells was
      unchanged by the addition of particles as determined by 3H-thymidine uptake.
      These data suggest that MIF expression may represent an independent macrophage
      response to locally high particle concentrations.

PMID- 10880236
TI  - Macrophage migration inhibitory factor increases MMP-2 activity in DU-145
      prostate cells.
AB  - Macrophage migration inhibitory factor (MIF) is a cytokine expressed by a number
      of different cell types and has been detected in prostatic glandular epithelial
      cells by immunohistochemistry. The goal of this study was to determine if in
      vitro cultured prostate cells produce this protein and some of the effects of MIF
      on these cells. Proliferation of normal prostate cells, the BPH-1 and DU-145
      established cell lines in the presence of MIF were assessed. ELISA was used to
      screen conditioned medium for the production of MIF, matrix metalloproteinase-2
      (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2). Zymogram
      electrophoresis gels determined the activities of secreted MMP-2. The amount of
      MIF in the conditioned medium detected after 72 h of growth in normal, BPH-1 and
      DU-145 cells was 2.9, 5.2 and 10.2 ng/ml/10(6)cells respectively. Exogenous
      addition of MIF (25 ng/ml) to cells cultured in vitro stimulated proliferation of
      all the cell types tested. MIF addition to proliferating DU-145 cells resulted in
      a two-fold increase in the relative amount of active MMP-2 as determined by
      zymogram gel analysis of conditioned medium.

PMID- 10880237
TI  - Oncostatin M suppresses EGF-mediated protein tyrosine phosphorylation in breast
      cancer cells.
AB  - The effect of oncostatin M (OM) on epidermal growth factor (EGF)-mediated protein
      tyrosine phosphorylation in an infiltrating ductal breast carcinoma cell line,
      H3922, was investigated by Western blot analysis. Pretreatment of H3922 cells
      with OM for 72 h suppressed EGF-stimulated protein tyrosine phosphorylation
      signals by 77%. Interestingly, pretreatment with OM for 6 or 48 h had little
      effect on these signals. EGF-mediated tyrosine phosphorylation of EGF receptor
      (EGFR) was suppressed by 55% in 72-h OM pretreated H3922 cells. No reduction in
      EGFR protein expression was detected in these cells. Flow cytometric analysis
      verified that OM does not suppress EGFR expression. The effect of OM could not be
      attributed to induction of protein tyrosine phosphatases. An H3922 subclone cell
      line, designated H3922-8, was found to exhibit no proliferative response to
      treatment with EGF. However, EGF-mediated protein tyrosine phosphorylation was
      detected in these cells. Radioligand EGF binding studies comparing H3922 to H3922
      8 cells indicated that the clonal cells apparently lack high affinity EGF
      receptors. The mechanism by which OM suppresses EGF-mediated tyrosine
      phosphorylation has not been completely characterized. However, the suppressive
      effect occurs regardless of whether the cells are acutely responsive (H3922) or
      virtually unresponsive (H3922-8) to EGF stimulation of cell growth.

PMID- 10880238
TI  - Interleukin 10 modulation of tumour necrosis factor receptors requires tyrosine
      kinases but not the PI 3-kinase/p70 S6 kinase pathway.
AB  - We have previously shown that interleukin (IL-)10-induced proliferation of the
      murine mast cell line D36, was dependent upon the activation of PI 3-kinase and
      p70 S6 kinase. Conversely, we were able to show that this pathway was not
      involved in the signal transduction pathway mediating IL-10 inhibition of pro
      inflammatory cytokine release from monocytes. We have extended these studies to
      investigate the induction of p75 tumour necrosis factor receptor (TNF-R)
      shedding, another anti-inflammatory property of IL-10. Using the inhibitors of PI
      3-kinase (LY294002 and wortmannin) and an inhibitor of p70 S6 kinase activation
      (rapamycin), we were able to show that this anti-inflammatory effect of IL-10 was
      not mediated by the PI 3-kinase/p70 S6 kinase pathway, indicating that another
      signalling cascade(s) was involved. Further studies also investigated the role of
      tyrosine kinases in the response to IL-10. Two distinct tyrosine kinase
      inhibitors, herbimycin and genistein affected the expression of TNF-R in response
      to IL-10 but, surprisingly, with opposite effects. However, both compounds
      inhibited the activation of both PI 3-kinase and p70 S6 kinase, with a
      concomitant inhibition of IL-10-induced proliferation. We observed that whilst
      tyrosine kinase activity was involved in the regulation of TNF-R expression, IL
      10-induced activation of JAK kinases was not sensitive to inhibition by the
      tyrosine kinase inhibitors. These data suggest that multiple unknown tyrosine
      kinases are mediating the IL-10-induced signal transduction pathways leading to
      the regulation of TNF-R expression and IL-10-induced proliferation.

PMID- 10880239
TI  - L929 cell conditioned medium protects RAW264.7 cells from oxidative injury
      through inducing antioxidant enzymes.
AB  - We have previously found that L929 cell conditioned medium (L929-CM) could
      protect mouse peritoneal macrophages from oxidative injury. To uncover the
      mechanism further, we investigated the effect of L929-CM on the oxidative injury
      caused by tbOOH to RAW264.7 cell lines. The results showed that L929-CM could
      protect RAW264.7 cells from oxidative injury (presented by cell morphology and
      cell survival rate), and L929-CM could also improve total superoxide dismutase
      (SOD), selenium-dependent and non-selenium-dependent glutathione peroxidase
      (SeGPx and non-SeGPx) activities in RAW264.7 cells. RT-PCR analysis showed that,
      L929-CM could induce plasma glutathione peroxidase (PLGPx) mRNA expression, while
      there was no inducing effect of L929-CM on phospholipid hydroperoxide glutathione
      peroxidase (PHGPx) mRNA expression in RAW264.7 cells. 5 microg/ml actinomycin D,
      30 microg/ml cycloheximide (de novo protein synthesis inhibitor) and 50 microg/ml
      acetovanilone (intracellular superoxide anion production inhibitor) had no
      effects in attenuating the induction of PLGPx expression by L929-CM.

PMID- 10880240
TI  - Pattern of cytokine expression by rat liver epithelial cells supporting long-term
      culture of human CD34(+)umbilical cord blood cells.
AB  - Fetal liver is the main site of haematopoiesis during mid-gestation. The adult
      liver still provides a favourable environment for extramedullary haematopoiesis.
      Nevertheless, regulation of liver haematopoiesis by cell-cell contacts or by
      cytokines remains poorly understood. Recently, we have shown that rat liver
      epithelial cells (RLECs) support long-term survival and multilineage
      differentiation of adult human CD34(+)and CD34(+)/CD38(-)haematopoietic cells
      obtained from granulocyte-colony stimulating factor mobilized peripheral blood
      and from bone marrow respectively. In addition, the importance of physical
      proximity between haematopoietic cells and RLECs was clearly demonstrated. Here,
      our findings give evidence that RLECs belonging to the epithelial but non
      parenchymal liver compartment also sustain the long-term production of
      progenitors from human CD34(+)umbilical cord blood cells. Moreover, to better
      analyse the regulation of haematopoiesis in this RLEC coculture model, we have
      investigated the cytokine expression by RLECs alone and by RLECs coming from
      coculture with CD34(+)cells from umbilical cord blood. We demonstrated that a
      broad spectrum of cytokines acting at different stages of haematopoiesis is
      produced by RLECs. Interestingly, an upregulation of leukemia inhibitory factor
      expression by RLECs in presence of CD34(+)haematopoietic cells was observed.
      These data suggest an important role of cell-cell interactions in the regulation
      of haematopoiesis.

PMID- 10880241
TI  - Comparative studies of the effects of recombinant GM-CSF and GM-CSF administered
      via a poxvirus to enhance the concentration of antigen- presenting cells in
      regional lymph nodes.
AB  - Repeated subcutaneous (s.c.) injections of recombinant granulocyte-macrophage
      colony-stimulating factor (recGM-CSF) for 4-5 days can enrich an immunization
      site with antigen-presenting cells (APC), which has been correlated with improved
      immune responses in experimental and clinical studies. A recombinant vaccinia
      virus encoding the GM-CSF gene (rV-GM-CSF) has been developed and can generate
      specific antitumour immunity in a whole tumour cell vaccine. In the present
      study, we examined whether rV-GM-CSF could produce and release GM-CSF locally
      which, in turn, might enrich a site of immunization for APC as previously shown
      for recGM-CSF. S.c. injection of rV-GM-CSF significantly (P<0.05) enhanced the
      percentage and overall number of APC, measured by class II expression levels, in
      the regional lymph nodes that drain the injection site. Dose- and temporal
      dependent studies showed class II expression levels in the draining lymph nodes
      were maximally enhanced 5-7 days after a single injection of 10(7)plaque-forming
      units (pfu) of rV-GM-CSF. Flow cytometry revealed that the increase in class II
      expression resulted from (i) a higher class II expression level on CD19(+)B cells
      and (ii) an increase in the number of CD11c(+)/class II(+)professional APC within
      the draining lymph nodes. Moreover, isolation of lymph nodes from rV-GM-CSF
      treated mice revealed their capacity to support higher levels of antigen-specific
      T cell proliferation and allospecific cytotoxic responses. A comparison between a
      single injection of rV-GM-CSF and a 4-day course of recGM-CSF revealed comparable
      changes in class II expression and functional T cell assays. GM-CSF can be
      delivered in a recombinant poxvirus, and the local production of the cytokine
      results in cellular and phenotypic changes that are similar to those of recGM
      CSF. The ability to utilize rV-GM-CSF as a single inoculum may be more compatible
      with traditional immunization strategies.

PMID- 10880242
TI  - Ganglioside control over IL-4 priming and cytokine production in activated T
      cells.
AB  - Our previous studies have shown that the enzymatic activities of Neu-1, an
      endogenous sialidase encoded in the murine MHC, are involved in promoting IL-4
      synthesis by naive CD4(+)T cells. Our present studies have characterized
      responsible sialoconjugate targets of Neu-1 and questioned possible biochemical
      mechanisms responsible for their regulatory influences on IL-4 gene expression.
      These studies determined that treatment of T cells with the naturally occurring
      ganglioside GM3 inhibited the production of IL-4 without affecting the production
      of IL-2. An analysis of IL-4-primed CD4(+)T cells further demonstrated that GM3
      treatment specifically inhibited the restimulated production of IL-4, IL-5 and IL
      13, without inhibiting the production of IL-2 and IFN-gamma. The inhibitory
      effects of GM3 could be overcome by treatment with thapsigargin or ionomycin,
      suggesting ganglioside regulation occurs upstream of activation-induced calcium
      mobilization. GM3 treatment attenuated the level of calcium influx following
      CD3epsilon crosslinking, and CD4(+)T cells from Neu-1-deficient B10.SM strain
      mice (neu-1(a)and IL-4-deficient) expressed reduced levels of intracellular
      calcium following activation. Our results indicate that activities by membrane
      gangliosides can influence the cytokine programs in CD4(+)T cells, possibly
      through the modulation of calcium responses induced by T cell activation.

PMID- 10880243
TI  - TNF-alpha and IL-1alpha induce apoptosis in subconfluent rat mesangial cells.
      Evidence for the involvement of hydrogen peroxide and lipid peroxidation as
      second messengers.
AB  - Apoptosis of mesangial cells (MC) plays a role in glomerulonephritis (GN). In
      this study we investigated cytokine-induced apoptosis of cultured rat MC by
      morphological and biochemical features. TNF-alpha and IL-1alpha induced apoptosis
      in rat MC in a time- and concentration-dependent fashion. RT-PCR experiments
      revealed that MC express the TNF-receptor 1 (p60) gene constitutively. TNF-alpha
      as well as IL-1alpha stimulated the production of reactive oxygen species (ROS)
      and induced lipid peroxidation. Coincubation with catalase inhibited TNF-alpha
      and IL-1alpha induced apoptosis as well as lipid peroxidation. TNF-alpha, but not
      IL-1alpha increased the expression of c-jun. These results provide evidence that
      TNF-alpha and IL-1alpha induce apoptosis in rat MC with hydrogen peroxide and
      lipid peroxidation as second messengers. Increased c-jun expression may be a
      downstream intracellular signal of TNF-alpha-, but not IL-1alpha-induced
      apoptosis.

PMID- 10880244
TI  - Tumour necrosis factor receptor I (p55) is upregulated on endothelial cells by
      exposure to the tumour-derived cytokine endothelial monocyte- activating
      polypeptide II (EMAP-II).
AB  - Endothelial monocyte activating polypeptide-II (EMAP-II) is an inflammatory
      cytokine known to have a role in neutrophil and macrophage chemotaxis and in
      apoptosis. It is a tumour-derived cytokine that sensitizes tumour vasculature to
      the effects of systemic TNF. In order to gain insight into the mechanism by which
      EMAP-II sensitizes vessels to TNF, we focused on its effects on TNF receptor
      expression. In human umbilical vein endothelial cells (HUVEC), TNF-R1 mRNA is
      increased four-fold following incubation with recombinant EMAP-II. Conditioned
      media from cell lines known to produce high levels of EMAP-II upregulated TNF-R1
      but not TNF-R2 by up to twenty-fold compared to media controls and low expressing
      cell lines; this effect was blocked by anti-EMAP-II antibody. Recombinant EMAP-II
      upregulated TNF-R1 expression by approximately six-fold. Analysis of HUVEC
      lysates by ELISA showed increased expression of TNF-R1 within 2 h; TNF-R2
      expression was unaffected by recombinant EMAP-II. Finally, immunohistochemistry
      of human melanomas in vivo showed that TNF-R1 staining is increased on the
      vessels of tumours known to express high levels of EMAP-II compared to low EMAP
      II expressing tumours. These results suggest that EMAP-II upregulates TNF-R1
      expression by endothelial cells both in vitro and in vivo. This induction of TNF
      R1 expression may be the mechanism by which EMAP-II sensitizes tumour endothelium
      to the effects of TNF leading to haemorrhagic necrosis.

PMID- 10880245
TI  - Selectivity release of the type II decoy IL-1 receptor.
AB  - The type II IL-1 receptor (IL-1RII) is a non-signalling molecule which acts as a
      decoy target for IL-1. Various signals (e.g. chemoattractants and phorbol ester)
      induce metalloprotease-mediated rapid shedding of the IL-1RII. The present study
      was designed to compare the susceptibility to shedding of the decoy IL-1RII vs
      the signalling IL-1RI. HEK 293 cells and COS cells were transfected with cDNAs
      encoding the human IL-1RI, IL-1RII or both. Slow spontaneous release and rapid
      phorbol ester-induced shedding were only observed for the decoy IL-1RII.
      Similarly, OVCAR-3 cells, which express substantial amounts of both IL-1RI and IL
      1RII, only released the IL-1RII. These results indicate that the IL-RII, but not
      the IL-1RI, is susceptible to proteolytic shedding, a finding consistent with the
      decoy function of this molecule.

PMID- 10880246
TI  - TNF-alpha is a potent inducer for IFN-inducible protein-10 in hepatocytes and
      unaffected by GM-CSF in vivo, in contrast to IL-1beta and IFN-gamma.
AB  - We have recently shown that IFN-inducible protein 10 (IP-10), a member of the CXC
      chemokine family, is induced in hepatocytes surrounded by infiltrative
      mononuclear cells in human livers with chronic hepatitis. Hence, we examined the
      kinds of stimuli that can induce IP-10 expression in hepatocytes in vivo. While
      the liver expressed three chemokine genes (IP-10, JE/MCP-1, KC/GRO) in a tissue
      specific fashion following systemic treatment with pro-inflammatory cytokines, IP
      10 mRNA expression showed the most marked liver-specificity. Pretreatment with GM
      CSF selectively inhibited IL-1beta, but not TNF-alpha-induced IP-10 mRNA
      expression. In situ hybridization analysis in the liver and Northern
      hybridization analysis in isolated liver cell fractions from rodents treated with
      pro-inflammatory cytokines revealed cellular sources of chemokine expression. IP
      10 mRNA expression in hepatocytes was induced by i.v. administration of TNF
      alpha, and to a much lesser extent in response to IL-1beta and IFN-gamma, whereas
      Kupffer cells and endothelial cells expressed IP-10 mRNA equivalently in response
      to these three stimuli. On the other hand, JE/MCP-1 mRNA expression was detected
      only in non-parenchymal cells in response to TNF-alpha and IL-1beta, but not in
      response to IFN-gamma. KC/GRO mRNA expression was also induced mainly in
      sinusoidal cells by treatment with TNF-alpha or IL-1beta, although it was
      detected to a lesser extent in hepatocytes. Our results demonstrated that
      chemokine induction is stimulus-, tissue- and cell type-specific and that IP-10
      (but not MCP-1) is inducible in hepatocytes by TNF-alpha most potently, even in
      the presence of GM-CSF, suggesting the specific role of TNF-alpha-induced IP-10
      on intralobular mononuclear infiltration in chronic hepatitis.

PMID- 10880247
TI  - Positive and negative hematopoietic cytokines produced by bone marrow endothelial
      cells.
AB  - Recently, cytokines and interleukins such as SCF, GM-CSF, G-CSF, TGF-beta, IL-6,
      IL-7, IL-8, IL-11 have been reported to be elaborated by endothelial cells. For
      further study, serum free bone marrow endothelial cell conditioned medium (BMEC
      CM) was collected and ultrafiltrated by using a centriprep 10. The concentrated
      retentate (R-BMEC-CM) contained some substances whose molecular weight was more
      than 10 000 daltons. The filtrate (F-BMEC-CM) contained some substances whose
      molecular weight was less than 10 000 daltons. The effects of R-BMEC-CM and F
      BMEC-CM on the growth of haematopoietic progenitors and the expression of
      cytokine and interleukin mRNAs of BMEC were investigated. The results showed that
      R-BMEC-CM stimulated the growth of CFU-GM, HPP-CFC, BFU-E, CFU-E, and CFU-Meg;
      while F-BMEC-CM inhibited the growth of these progenitors. Using the method of
      hybridizing to the Atlas cDNA Array, we were able to detect the presence of mRNAs
      of cytokines and interleukins in bone marrow endothelial cells. Our finding of
      the existence of mRNAs of SCF, GM-CSF, IL-6, TGF-beta, IL-1, and IL-11 in these
      cells was in agreement with the data reported previously. Furthermore, we
      detected mRNAs of MIP-2, Thymosion-beta4, PDGF, MSP-1, IFN-gamma, IL-13 and
      inhibin, which are related to haematopoiesis. Among these cytokines and
      interleukins, SCF, GM-CSF, IL-6, IL-1, and IL-11 are haematopoietic stimulators
      which may be responsible for the stimulative effects on the growth of
      haematopoietic progenitors. One of our new findings, the thymosin-beta4, is a
      small molecular haematopoietic inhibitor. It may be responsible for the
      inhibitory effect of F-BMEC-CM on haematopoietic progenitors. The presence of
      mRNAs of BMP, MSP-1, MIP-2, PDGF and IL-13 suggests that bone marrow endothelial
      cells might elaborate these substances. Their influence on haematopoietic
      progenitors needs further study.

PMID- 10880248
TI  - Innate resistance to experimental African trypanosomiasis: differences in
      cytokine (TNF-alpha, IL-6, IL-10 and IL-12) production by bone marrow-derived
      macrophages from resistant and susceptible mice.
AB  - Resistance to African trypanosomiasis is under multigenic control. BALB/c mice
      are highly susceptible while C57Bl/6 mice are relatively resistant. Macrophages
      eliminate opsonized trypanosomes from the bloodstream and are involved in
      immunosuppression. We therefore investigated the production of a number of
      cytokines (IL-10, IL-6, TNF-alpha and IL-12) by bone marrow-derived macrophages
      (BMDM) from C57Bl/6 and BALB/c mice following challenge with either Trypanosoma
      congolense or Trypanosoma brucei. BMDM from C57Bl/6 mice, upon challenge with
      whole cell extracts (WCE) of T. congolense or T. brucei, produced significantly
      more TNF-alpha and IL-12 than those from BALB/c mice. The production of these
      cytokines was significantly enhanced by pretreatment of the cells with IFN-gamma.
      BMDM from BALB/c mice, however, produced significantly more IL-6 and IL-10 than
      those from C57Bl/6 mice. In contrast to LPS stimulation, simultaneous treatment
      of cells with WCE and IFN-gamma enhanced IL-10 synthesis by BMDM from BALB/c
      mice. These results indicate that cytokine genes are differentially regulated in
      macrophages from trypanosome-susceptible and -resistant mice and are consistent
      with our previous findings wherein retrovirus-immortalized macrophage cell lines
      from BALB/c and C57Bl/6 mice produce differential amounts of cytokines after
      phagocytosis of trypanosomes.

PMID- 10880249
TI  - IL-12-encoding plasmid has a beneficial effect on spontaneous autoimmune disease
      in MRL/MP-lpr/lpr mice.
AB  - Systemic lupus erythematosus (SLE) is characterized by immune abnormalities
      explained by the overproduction of Th(2)cytokines such as autoantibody production
      and polyclonal B cell activation. We examined the effect of administering a DNA
      plasmid encoding IL-12 on the lupus-like disease of MRL/MP-lpr/lpr (MRL/lpr)
      mice. Treatments were delivered intramuscularly every 4 weeks, starting at 4
      weeks of age. This intervention significantly inhibited the accumulation of CD4(
      )CD8(-)T cells, and reduced lymphadenopathy and splenomegaly. A significant
      decrease in serum IgG anti-DNA autoantibody titers was observed, and plasmid IL
      12 therapy was also associated with a reduction in the proteinuria and
      glomerulonephritis characteristic of this disease. Serum IFN-gamma level was
      increased by inoculating IL-12 encoding plasmid, suggesting that the cytokine
      balance was skewed towards Th(1). The clinical implications of this suppression
      of autoimmune disease are also discussed.

PMID- 10880250
TI  - The co-ordinated cytokine/hormone response to acute injury incorporates leptin.
AB  - Recent studies have implicated leptin as a "stress" hormone and highlighted its
      association with increases in inflammatory cytokines, C-reactive protein and
      cortisol. In order to investigate the exact temporal leptin response to stress we
      undertook a detailed longitudinal study of circulating leptin concentrations
      during the well defined surgical injury of cholecystectomy. Circulating
      concentrations of cortisol, free fatty acids, leptin and C-reactive protein were
      measured at 3, 6, 9, 12, 18, 24, 48 and 72 h from the start of surgery in nine
      patients. There was a significant correlation between baseline concentrations of
      leptin and BMI (r=0. 893, P<0.001). Over the 72 h from the start of surgery there
      were significant (P<0.05) increases in the concentrations of all analytes (peak
      median concentrations); cortisol (6 h), free fatty acids (9 h), leptin (18 h) and
      C-reactive protein (48 h). Interestingly the timing of the leptin peak at
      approximately 18 h after an acute inflammatory stimulus is exactly the same as
      previously reported for interleukin 6. These data support the suggestion that the
      relationship between cortisol and leptin mirrors that of cortisol and another
      cytokine, interleukin 6, i.e. stimulatory in acute and suppressive in chronic
      situations. They also imply a physiological role for leptin in acute injury.

PMID- 10880251
TI  - Involvement of alpha-2-macroglobulin receptor in clearance of interleukin 8-alpha
      2-macroglobulin complexes by human alveolar macrophages.
AB  - The purpose of this study was to determine if interleukin 8 (IL-8) in complex
      with alpha2-macroglobulin (alpha-2-M) can be taken up by human alveolar
      macrophages. First, we demonstrated that human alveolar macrophages have
      receptors for alpha-2-M but not IL-8. The binding of(125)I-labeled alpha-2-M to
      the cells was specific and saturable, whereas(125)I-labeled recombinant human IL
      8 (rhIL-8) did not bind to macrophages. However,(125)I-rhIL-8-alpha-2-M complexes
      bound to macrophages, and unlabeled alpha-2-M competed for the binding. We then
      cultured the cells in the presence of(125)I-rhIL-8-alpha-2-M complexes,(125)I
      rhIL-8 alone or buffer for 24 h. Macrophages were lysed, and the released
      radioactivity measured. IL-8 concentrations in supernatants and cells were also
      measured using an IL-8 ELISA. When the macrophages were incubated with(125)I-rhIL
      8-alpha-2-M complexes there was a significant amount of IL-8 associated with the
      cells. However, this was not the case when the cells were incubated with(125)I-
      rhIL-8 alone suggesting that only these complexes were taken-up by human alveolar
      macrophages. Furthermore, the clearance of complexes was specifically inhibited
      by a monoclonal antibody against the 515-kDa subunit of the alpha-2-M receptor
      (alpha-2-MR) but not by an isotopic mouse IgG1. The study shows an important
      clearance mechanism for IL-8 in the lung.

PMID- 10880252
TI  - Regulation of chemokine expression by IL-10 in lung inflammation.
AB  - We have been interested in understanding the mechanisms regulating the
      inflammatory process underlying acute lung injury. The current studies have
      employed a model of acute lung inflammation in mice triggered by bacterial
      lipopolysaccharide. The development of this injury was associated with increased
      expression of the chemokines, MIP-1alpha and MIP-2, that coordinate recruitment
      of neutrophils to the lung. IL-10 is a potent, endogenous anti-inflammatory
      molecule that has been shown to decrease lung inflammation partly on the basis of
      TNF-alpha and IL-1beta inhibition. In these studies we tested the hypothesis that
      endogenous IL-10 modulates chemokine expression using the IL-10 knock-out mouse,
      and then explored the molecular mechanisms by which IL-10 might do so. The
      results demonstrate that significant elevations in both chemokines were observed
      in the absence of IL-10 and that these findings were associated with significant
      increases in lung neutrophil accumulation. In vitro studies defined two, gene
      specific, mechanisms by which IL-10 regulated chemokine expression: mRNA
      destabilization and NF-kappaB inhibition. These results suggested that IL-10 is
      an important, endogenous regulator of chemokine expression in acute lung
      inflammation.

PMID- 10880254
TI  - Presence of interleukin 10 in the serum and blister fluid of patients with
      pemphigus vulgaris and pemphigoid.
AB  - Interleukin 10 (IL-10) is an immunoregulatory cytokine produced by T lymphocytes
      and macrophages. Recently, it has been suggested that IL-10 may be involved in
      the pathogenesis of various inflammatory and autoimmune diseases. Using an ELISA
      we investigated the presence of IL-10 in the serum and blister fluid of pemphigus
      vulgaris (PV) patients with active disease and those in prolonged clinical
      remission compared with normal controls. Sera from patients with bullous
      pemphigoid (BP), ocular cicatricial pemphigoid (OCP), oral pemphigoid (OP) and
      blister fluid from five patients with BP were also studied. Increased levels of
      IL-10 were detected in the sera of 87.5% of patients with active PV and were
      statistically significant (P=0.0003) when compared with levels in normal human
      serum. Lower levels of IL-10 were detected in 12.5% PV patients in remission and
      were statistically significant (P=0.0001) when compared with levels in patients
      with active disease. Levels of IL-10 were detected in sera of 4.6% (1 of 24) of
      the normal controls. The levels of IL-10 were approximately four times higher in
      blister fluids than levels in the serum in the same PV patients. This difference
      was highly statistically significant (P=0.0008). A correlation was observed
      between serum levels of IL-10 and titres of pemphigus autoantibodies and with
      disease severity. Elevated level of IL-10 was detected in the blister fluid from
      five BP patients. Levels of IL-10 in the sera of patients with BP, OCP and OP
      were not significantly increased. These preliminary data suggest that IL-10 in
      concert with other cytokines may play an important role in the pathogenesis of PV
      and BP.

PMID- 10880253
TI  - Quantitative comparison of cytokine mRNA and inflammatory responses in cutaneous
      late phase allergic reactions.
AB  - The aim of this study was to quantitatively compare expression of mRNA for IL-5
      and IFN-gamma with the frequency of mRNA-positive cells, total and activated
      eosinophils, neutrophils, lymphocytes, and vessels expressing adhesion molecules.
      Replicate biopsies of skin LPR to pollen antigens (Ag) and control injection
      sites (B) at 6 and 24 h were assessed for: (1) mRNA for IL-5 and IFN-gamma by
      quantitative RT-PCR (QC-RT/PCR); (2) frequency of cells expressing mRNA for IL-5
      and IFN-gamma by in situ hybridization (ISH); (3) inflammatory cells and adhesion
      molecule expression. More mRNA for IL-5 was found in Ag- than in B-injected sites
      at 6 and 24 h by both QC-RT/PCR and ISH. Small amounts of mRNA for IFN-gamma were
      detected in Ag sites by QC-RT/PCR at 6 and 24 h, but were not significantly
      different than at B sites. The frequency of IFN-gamma mRNA(+)cells was higher in
      Ag than in B sites at 6 h. There was no correlation between the amount if IL-5
      detected by QC-RT/PCR and frequency of IL-5 mRNA(+)cells by ISH. These findings
      also did not correlate with the degree of inflammatory responses. IN CONCLUSION:
      (1) greater IL-5 than IFN-gamma deposition in Ag sites suggests Th(2)predominance
      in LPR; (2) lack of correlation between QC-RT/PCR and ISH findings may reflect
      varying mRNA content of inflammatory cells.

PMID- 10880255
TI  - Elevated plasma TGF-beta1 in renal diseases: cause or consequence?
AB  - We previously reported elevated levels of TGF-beta1 in patients with renal
      carcinoma. Certain aspects led us to ask whether they might be caused by chronic
      damage to the kidney(s). Here we report on an extended set of patients with
      various renal diseases, lung cancer, humoral immunodeficiency and controls. For
      latent TGF-beta1 in plasma, we find that the control, immunodeficiency, lung
      cancer and kidney transplant groups do not differ significantly (means, 7.0-8.8
      ng/ml). Also, acute short-term renal stress (extracorporal lithotrypsy) does not
      lead to an increase of TGF-beta1. However, the pyelonephritis patients present
      with levels of 19.0 ng/ml, chronic extracorporal dialysis patients with 15.5
      ng/ml, and renal cell carcinoma patients with 22.8 ng/ml. For active TGF-beta1
      these findings are exactly recovered. For serum levels, only the renal carcinoma
      group presents with significantly elevated levels of TGF-beta1. Kidney
      transplantation seems to normalize TGF-beta1 levels, while in the kidney cancer
      patients surgery has an effect only in part of the group. We conclude that
      elevated plasma TGF-beta1 levels are common in at least two chronic renal disease
      conditions, and that it normalizes with restoration of renal function. It is
      tempting to speculate that chronic elevation of TGF-beta1 in these patients may
      be critically involved in these conditions predisposing to renal cancer.

PMID- 10880256
TI  - Contribution of interleukin 17 to synovium matrix destruction in rheumatoid
      arthritis.
AB  - Interleukin (IL-)17 is a T cell-derived pro-inflammatory cytokine produced by RA
      synovium. We studied the role of IL-17 in the synovium cytokine network to
      determine whether it can influence the inflammatory and destructive pattern
      characteristic of RA. Herein, we investigated whether the production and action
      of MMP-1 and its inhibitor TIMP-1 could be modulated by IL-17 in the presence of
      pro-inflammatory cytokine (IL-1) and anti-inflammatory cytokines (IL-4, IL-13, IL
      10). The effect of the blockade of endogenous IL-17 on the secretion of MMP-1 and
      TIMP-1 by RA synovium and matrix destruction was also studied. IL-17 increased
      the spontaneous production of MMP-1 by synoviocytes five-fold. IL-1 was more
      potent since it increased MMP-1 production nine-fold. Addition of IL-4, IL-13 and
      IL-10 to synoviocyte cultures reduced the spontaneous production of MMP-1 and
      induced TIMP-1 production by synoviocytes stimulated with IL-17 or/and IL-1beta.
      In the presence of anti-IL-17 blocking mAb, MMP-1 production and collagenase
      activity by RA synovium was reduced by 50% and associated with a 50% reduction in
      type I collagen C-telopeptide fragments (CTX) released in the supernatants,
      demonstrating the direct contribution of IL-17 in destruction. IL-17 and its
      producing T cells appear to contribute to the inflammatory process involved in
      the rheumatoid lesion.

PMID- 10880257
TI  - Inhibition of HMG-CoA reductase activity by hypercholesterolaemia reduces
      leukocyte recruitment and MCP-1 production.
AB  - To clarify the relationship between cholesterol homeostasis and inflammation we
      studied the effect of hypercholesterolaemia on in vivo cytokine production and
      leukocyte migration, in a murine model of local inflammation.
      Hypercholesterolaemia reduced of 40% the leukocyte recruitment by inhibiting
      interleukin-6 and monocyte chemotactic protein-1 production in the pouch exudate,
      without affecting vascular permeability or leukocytes motility.

PMID- 10880258
TI  - IGF-II and IL-2 act synergistically to alter HDAC1 expression following
      treatments with trichostatin a.
AB  - Histone deacetylases play key roles in the regulation of gene transcription.
      Studies have shown that expression of interleukins IL-2 and IL-8, and insulin
      like growth factor 2 (IGF2) are affected by treatment with histone deacetylase
      inhibitors. We have previously shown that the gene for histone deacetylase 1
      (HDAC1) is upregulated following treatment with TSA. The murine homologue of this
      gene has been reported to be inducible by IL-2. In this study, we have examined
      the effects IL-2, IGF-II and TSA have on HDAC1 expression in the human
      hepatocellular carcinoma derived cell line Hep3B. Our results indicate that in
      contrast to the mouse, HDAC1 is not inducible by IL-2. However, in TSA treated
      cells, IL-2 and IGF-II were found to act synergistically to reduce TSA induced
      HDAC1 mRNA levels almost to normal.

PMID- 10880259
TI  - IL-6 promoter is modulated by the 24 kDa FGF-2 isoform fused to the hormone
      binding domain of the oestrogen receptor.
AB  - Fusion proteins consisting of the 24 kDa nuclear form of basic fibroblast growth
      factor (FGF-2), associated with the hormone binding domain of oestrogen receptor
      (HBD), convey oestrogen inducibility to FGF-2. When stable HBD-FGF-2 HeLa cell
      lines were transiently transfected with an interleukin 6 (IL-6) construct, the IL
      6 promoter activity was downregulated by the addition of oestradiol. Moreover, in
      these cell lines, the function of the FGF-2 nuclear localisation sequence was
      abolished by its fusion to HBD, while addition of oestradiol restored the
      location of the chimera to the nucleus.

PMID- 10880260
TI  - Regulation of transforming growth factor-beta secretion by human peritoneal
      mesothelial and ovarian carcinoma cells.
AB  - This study was conducted to compare the secretion of TGF-beta isoforms by human
      ovarian carcinoma (OVCA) cell lines (n=12) and human peritoneal mesothelial cells
      (HPMC;n=6) and to examine the regulation of their production by inflammatory
      cytokines. TGF-beta isoforms were furthermore analysed in OVCA-associated ascitic
      fluids. HPMC constitutively produced considerable amounts of TGF-beta1 (median 42
      pg/10(5)cells; range 7-98) but only minimal amounts of TGF-beta2 (median 0.8
      pg/10(5)cells; range 0-1.5). Treatment of HPMC with IL-1beta (10 ng/ml) resulted
      in a significant elevation of the secretion of both TGF-beta1 (median 187
      pg/10(5)cells; range 71-264;P<0.001) and TGF-beta2 (median 1.8 pg/10(5)cells;
      range 0-13;P<0.01). In OVCA TGF-beta1 and TGF-beta2 were detected in 7/12 and
      11/12 of the cell lines, respectively. The levels detected varied widely for TGF
      beta1 (median 25 pg/10(5)cells; range 0-410) as well as for TGF-beta2 (median 14
      pg/10(5)cells; range 0-419) and there was no correlation between the two
      isoforms. In contrast to HPMC, TGF-beta secretion by OVCA was not affected by any
      of the inflammatory cytokines tested. TGF-beta3 could not be detected in
      supernatants, neither in OVCA nor in HPMC. In ascitic fluids the median level of
      TGF-beta1 (median 5443 pg/ml; range 737-14687) was 10-fold higher than the level
      of TGF-beta2 (median 545 pg/ml; range 172-3537). The present data provide a model
      for the analysis of the molecular mechanisms of aberrant TGF-beta production by
      OVCA and support the hypothesis that HPMC are an important source of ascitic TGF
      beta.

PMID- 10880261
TI  - Y-24180, an antagonist of platelet-activating factor, suppresses interleukin 5
      production in cultured murine th(2)cells and human peripheral blood mononuclear
      cells.
AB  - Interleukin (IL)-5 has been shown to play an essential role in the pathogenesis
      of airway inflammation. We investigated the effect of 4-(2-chlorophenyl)-2-[2-(4
      isobutylphenyl)ethyl]-6, 9-dimethyl-6 H -thieno[3,2- f ][1,2,4]triazolo[4,3-
      a][1,4]diazepine (Y-24180), an antagonist of platelet-activating factor (PAF), on
      the production of IL-5 in cultured D10.G4.1 cells, a murine Th(2)clone, and human
      peripheral blood mononuclear cells (PBMC). As a result, Y-24180 was found to
      suppress both the mRNA expression of IL-5 and the subsequent secretion of this
      cytokine in antigen-stimulated D10.G4.1 cells. Y-24180 also suppressed the
      production of IL-4, another Th(2)type cytokine, at the level of mRNA expression,
      however, it hardly affected the mRNA expression for IL-6 or IL-10, thus
      indicating it to have a selective action against IL-5 and IL-4. The suppressive
      effect of Y-24180 on the secretion of IL-5 by human PBMC was more potent than
      that of WEB2086, which is another PAF-antagonist. These results suggest that Y
      24180 suppresses IL-5 production through a common pathway which also affects the
      production of IL-4, even though the mechanism remains to be elucidated as to
      whether the PAF-antagonistic actions are involved or not.

PMID- 10880262
TI  - Cytokine production by in vitro processed and unprocessed haematopoietic cells.
AB  - The studies described here demonstrate that in vitro processing of cells before
      extraction of RNA has a major effect on the number and type of cytokine
      transcripts present within MDS and leukemia cells. Transcripts for GM-CSF, a
      cytokine whose production by leukemia cells is believed to play an important role
      in the pathogenesis of leukemia, was not detectable in 12/13 unprocessed AML
      specimens, in 12/12 MDS specimens, or in 7/7 CML specimens but once detected in
      many specimens after processing. These data strongly suggest that leukemia cell
      production of GMCSF rarely occurs in vivo.

PMID- 10880263
TI  - Regulation of interleukin 6 production in a human gastric epithelial cell line
      MKN-28.
AB  - Interleukin (IL-) 6 is closely related to gastrointestinal diseases. The question
      of whether gastric epithelial cell contributes to IL-6 production remains
      undefined. We aim to evaluate the regulatory pathway of IL-6 expression in
      gastric epithelial cells, by using different inflammatory cytokines, endotoxin,
      or protein kinase modulators. IL-6 was measured by ELISA. Phorbol-12-myristate-13
      acetate (PMA), calcium ionophore A23187, TNF-alpha, IL-1beta, oncostatin M (OSM)
      but not lipopolysaccharide stimulated IL-6 production from gastric epithelial
      cell line MKN-28. Blocking protein tyrosine kinase (PTK) activation by herbimycin
      A or genistein, or blocking NF-kappaB activation by pyrrolidinedithiocarbamate,
      reduced the IL-6 expression induced by TNF-alpha, IL-1beta and OSM. Dexamethasone
      mimicked this effect. Protein kinase (PK) C inhibitor only reduced the PMA and
      OSM induced IL-6 production. Both inhibitors and activators for PKA and G-protein
      as well as IL-10 had no effects on IL-6 expression. These results indicate that
      inflammatory cytokines are crucial for IL-6 regulation in gastric epithelial
      cells. The IL-6 signal pathway is mediated through PTK, NF-kappaB, and also
      involve PKC, intracellular calcium and sensitive to dexamethasone, but is not
      related to PKA, G-protein and IL-10.

PMID- 10880264
TI  - Mechanisms of CD26/dipeptidyl peptidase IV cytokine-dependent regulation on human
      activated lymphocytes.
AB  - Among the cellular pathways activated by IL-12, we had previously found that both
      the percentage and intensity of CD26(+)cells in the PHA-stimulated T cells
      increased when IL-12 was present (independently of its CD4 or CD8 phenotype).
      Now, we examined the molecular mechanisms of this IL-12-mediated effect. The IL
      12 regulation pathway is dependent of de novo protein synthesis and independent
      of cytokine secretion. Our results show two transcripts for CD26 in PBMC for the
      first time and no regulation by ILs at this level. Furthermore, secretion of the
      serum forms of CD26/DPPIV were not affected by IL-12. Interestingly, assays with
      neutralizing mAbs against TNF-alpha suggest that this cytokine negatively
      modulates CD26 expression. The fact that translation and probably translocation
      of CD26 toward the cell surface can be regulated by IL-12 and TNF-alpha reveals
      new aspects about the control of this T(H1)marker.

PMID- 10880265
TI  - High cytosolic pool of p75 TNF receptors and delayed surface downmodulation by
      mononuclear cells from non-hodgkin's lymphoma patients.
AB  - Analysis of the expression of TNF-Rs on fresh peripheral blood mononuclear cells
      (PBMNC) by Scatchard analysis showed that Gr I (stages I and II) but not Gr II
      (stages III and IV) NHL patients have a significantly higher expression of
      surface TNF-Rs than normal controls. A rapid decrease in the binding of
      radiolabelled anti-p75 TNF-R Mab which gradually increased after 16 h was seen in
      normal controls, while NHL patients showed a rapid increase in the binding of the
      Mab after activation of cells and a decrease in binding was observed only after
      24 h. Western blot analysis for normal controls showed a weak presence of the 42
      kDa fragment only, while the cytosolic extracts from fresh PBMNCs of NHL patients
      showed presence of both intact p75 TNF-R, as well as a 42 kDa fragment
      corresponding to a soluble form of p75 TNF-R. Our results suggest that increased
      cytosolic pools of TNF-R in NHL patients might contribute to a rapid increase in
      its surface expression following activation of cells.

PMID- 10880266
TI  - Effect of RNA from brain of immunized mice on the specific immune response.
AB  - The objective of the investigation was to study the influence of RNA isolated
      from the brains of immunized mice on the immune response in syngeneic recipients.
      (CBAxC57BL/6)F1 male mice immunized by SRBC and RRBC were used for isolation of
      experimental RNA. Mice injected with medium 199 were used for isolation of
      control RNA. Experimental and control RNA was injected into syngeneic mice
      recipients immunized by SRBC, RRBC or rat RBC preliminary. It was shown that
      experimental RNA stimulate the specific immune response only.

PMID- 10880267
TI  - Diurnal variations of serum GM-CSF levels.
AB  - We aimed to investigate the daily variations of serum granulocyte-macrophage
      colony-stimulating factor (GM-CSF) levels and to correlate them with peripheral
      blood cells counts. Venous blood samples from eleven healthy volunteers were
      taken four times a day, being at 08:00, 14:00, 20:00 and 02:00h and serum GM-CSF
      levels measured by ELISA. We could not find a significant overall difference
      among GM-CSF levels at four different times of the day using the Friedman test.
      On the other hand, serum GM-CSF levels at night (20:00h) were found to be
      significantly increased when compared to the morning levels (08:00h) using the
      Wilcoxon test (P=0. 022). The levels of lymphocytes and white blood cells (WBCs)
      at 20:00h were also higher than the morning levels (08:00h) as expected. While
      there was a strong relationship between the morning levels of GM-CSF (08:00h) and
      all measurements of peripheral blood cells during the day, the levels of GM-CSF
      measured at 02:00, 14:00 and 20:00h were found to be significantly correlated
      with only the WBC levels. It was concluded that there may be a significant
      difference between morning and night levels of GM-CSF and morning levels of GM
      CSF may be more important in the regulation of WBC counts during the day. These
      variations warrant further studies about diurnal rhythms of haematopoiesis
      chronotherapy with CSFs.

PMID- 10880268
TI  - Changes in plasma IL-1beta, TNF-alpha and IL-6 after total hip replacement
      surgery in general or regional anaesthesia.
AB  - Different anaesthetic methods influence the neuro-immuno-endocrine biologic
      responses to surgery and may thus possibly interfere with the postoperative
      course and development of complications. The neuroendocrine system is closely
      related to the cytokine network. In this study, the effects of general
      anaesthesia (n=6) and regional spinal/epidural anaesthesia (n=6) on the cytokine
      response (IL-1beta, TNFalpha, IL-6) to uncemented total hip replacement surgery
      were evaluated. The postoperative clinical course was uneventful in every case.
      In both groups, only very low values of plasma IL-beta were measured
      perioperatively, whereas plasma IL-6 increased postoperatively with peak values 4
      h after surgery. The changes in plasma TNF-alpha were not significant. No
      significant differences in plasma TNF-alpha or IL-6 were found between patients
      operated in general or in regional anaesthesia. This suggests minor influence of
      plasma cytokines on the possible beneficial effects of regional anaesthesia on
      the clinical course after surgery in low risk patients. There were slightly
      higher TNF-alpha and IL-6 levels after the operation and significantly lower
      cortisol levels during the operation in the regional anaesthesia group compared
      to the general anaesthesia group, giving rise to a significant inverse
      correlation between peak values of IL-6 and peak values of cortisol. This
      supports the theory that after surgery the inhibitory effect of cortisol on
      monocyte cytokine production overrides adrenergic stimulation.

PMID- 10880270
TI  - In memoriam richard N. Lolley (1933-2000)

PMID- 10880269
TI  - An imbalance between pro- and anti-inflammatory cytokines, a characteristic
      feature of old age.

PMID- 10880271
TI  - Benzalkonium chloride and gentamicin cause a leak in corneal epithelial cell
      membrane.
AB  - The purposes of this study are to characterize the pathophysiological effects of
      benzalkonium chloride and gentamicin on corneal epithelial cells and to determine
      the concentration dependent effect of these agents on membrane currents of these
      cells. Rabbit corneal epithelial cells were isolated and subdivided into small,
      medium and large cells according to their cell capacitance. Using whole cell
      clamp technique, potassium current of corneal epithelial cells was recorded.
      Transmembrane current was measured again after bathing in benzalkonium chloride
      1, 3, 10, 30 and 100 micrometer ml(-1)for 3 min. The effect of gentamicin was
      tested at concentrations of 0.4, 1.0, 2.0, 4.0 and 10 mg ml(-1). Synergistic
      effect of gentamicin of the above mentioned concentrations in the presence of
      benzalkonium chloride 1 microgram ml(-1)was also measured. We found that small
      corneal epithelial cells had the highest depolarization-gated, outward potassium
      current density and large cells had the lowest current density, while medium
      cells had a current density in between. Benzalkonium chloride induced a
      concentration dependent increase in the leak current with increasing
      concentration from 1 to 100 microgram ml(-1). The increase of leak current in
      medium and large cells was less than that in the small cells. Gentamicin also
      caused a concentration dependent increase in leak current density from 0.4 to
      10.0 mg ml(-1). The increase in leak current density was statistically
      significant when the concentration was 2.0 mg ml(-1)or higher in small corneal
      epithelial cells and 1.0 mg ml(-1)or higher in the medium and large cells.
      Benzalkonium chloride 1.0 microgram ml(-1)augmented the effect of gentamicin on
      epithelial cell membrane. The extent of enhancement was more prominent in larger
      than smaller cells. Using whole-cell clamp technique, we were able to determine
      the threshold concentration of gentamicin and benzalkonium chloride on the
      integrity of corneal epithelial cell membrane. The toxic action of both agents is
      mediated by an increase in leak current. We propose that the whole-cell clamp
      technique is a sensitive and useful tool in determining cytotoxic effects of
      various agents.

PMID- 10880272
TI  - Lacrimal gland epithelial cells stimulate proliferation in autologous lymphocyte
      preparations.
AB  - Autoimmune dacryoadenitis is a frequent cause of lacrimal insufficiency. In order
      to test hypotheses regarding mechanisms that can trigger this syndrome, we
      developed a method to obtain a preparation of rabbit lacrimal gland epithelial
      cells essentially free of immune-system cells. The method relies on controlled
      digestion to disperse lacrimal acini, and recovers acini by filtration through
      various sizes of nylon mesh. Purity and integrity of the preparation were
      established qualitatively using light and electron microscopy. Contamination by
      immune-system cells was quantitated by immunohistochemistry using anti-CD18, and 
      RTLA (rabbit thymic lymphocyte antigen) antibodies. The novel method produced
      preparations of highly-purified lacrimal gland epithelial cells (pLGEC) with
      expected morphological characteristics with less than 1.5% of the cells staining
      for CD18 or RTLA. The method also yielded preparations of lacrimal gland
      interstitial cells (LGIC) enriched for lymphocytes; in these preparations either
      CD18 or RTLA were detected on nearly 10% of the cells. pLGEC promoted
      proliferation in preparations of autologous splenic lymphocytes (SPL) that was
      blocked by anti-MHC class II but not anti-MHC class I antibodies. This
      observation, combined with the apparent requirement that pLGEC must contact the
      autologous lymphocyte preparation to promote proliferation, supports the
      hypothesis the proliferation arises from antigen-presentation via MHC class II by
      pLGEC.

PMID- 10880273
TI  - Autologous lacrimal-lymphoid mixed-cell reactions induce dacryoadenitis in
      rabbits.
AB  - Autoimmune dacryoadenitis, such as occurs in Sjogren's syndrome, is a frequent
      cause of lacrimal insufficiency, which in turn can cause dry eye. Rabbits are
      used frequently to test ocular therapies. Our goal is to develop a rabbit model
      of autoimmune dacryoadenitis to identify and test candidate therapies. Our
      approach arises from the observations that lacrimal gland epithelial cells
      stimulate proliferation in cultured autologous lymphocyte preparations and that
      an anti-MHC II antibody blocks this proliferation. The purpose of this study was
      to determine if injecting this proliferating autologous mixed cell reaction could
      induce dacryoadenitis in rabbits. After establishing that irradiated lacrimal
      gland epithelial cells stimulate proliferation in autologous peripheral blood
      lymphocytes, irradiated cells from a single lacrimal gland were co-cultured with
      autologous lymphocytes and after 5 days the mixed cell reaction, or components of
      the reaction, were injected into the contralateral lacrimal gland of the donor
      rabbit. After 2 weeks, the injected glands were removed and lymphocytic
      infiltration quantitated using digital image analysis of immunostained
      histological sections. Injecting an autologous mixed cell reaction of co-cultured
      irradiated lacrimal gland epithelial cells and lymphocytes reliably induced
      abundant periductal foci of >200 lymphocytes expressing CD18 and/or a rabbit
      thymic lymphocyte antigen (RTLA). Injection of medium or autologous lymphocytes
      alone elicited little response; injections of lymphocytes cultured with lysates
      of lacrimal gland epithelial cells elicited variable, modest responses. These
      lysates did not stimulate proliferation in the mixed cell reaction and
      proliferation was not observed if a porous membrane separated co-cultured
      lacrimal gland cells and lymphocytes. The results demonstrate that injecting an
      autologous mixed cell reaction of lacrimal gland epithelial cells and lymphocytes
      reliably creates a model of autoimmune dacryoadenitis. The relative
      ineffectiveness of components of the reaction to do the same supports the
      hypothesis that lacrimal gland epithelial cells trigger or exacerbate lacrimal
      autoimmune disease by presentation of autoantigens via MHC II. This experimental
      system can aid efforts to further understand mechanisms of diseases, and to
      identify and test candidate therapies.

PMID- 10880274
TI  - The influence of corneal stromal matrix proteins on the migration of human
      corneal fibroblasts.
AB  - Motivated by the alterations seen in the corneal matrix composition after
      photorefractive keratectomy and the migration of corneal keratocytes seen
      following this procedure, the locomotor response of corneal stromal fibroblasts
      to various extracellular matrix proteins was determined. In addition, the
      involvement of integrin mediated attachment to the matrix proteins was
      investigated. Quantitative invasion assays were performed using collagen gels,
      supplemented with either fibronectin, tenascin, collagen type V, collagen type
      VI, chondroitin sulfate or keratan sulfate. The ultrastructure of the gels was
      visualized by scanning electron microscopy and related to the migration results.
      The extent of alpha(1)beta(1), alpha(2)beta(1), alpha(3)beta(1)and
      alpha(5)beta(1)integrin mediated attachment to the matrix proteins was evaluated
      using blocking antibodies. Fibronectin increased corneal fibroblast migration
      significantly, and served as an excellent substrate for cellular attachment,
      mediated by the alpha(5)beta(1)integrin. Addition of tenascin to the fibronectin
      containing gels disrupted these effects, while attachment to this matrix also
      involved the integrins alpha(2)beta(1)and alpha(3)beta(1). Chondroitin sulfate
      and collagen types V and VI primarily altered the structure of the collagen
      matrix, resulting in an inhibition of migration by the collagens and an increase
      by chondroitin sulfate. They all served as poor substrates for attachment. Thus,
      the migratory activity of corneal fibroblasts in vitro is influenced by the
      composition of the surrounding extracellular matrix, either by integrin mediated
      cell-matrix interactions or through matrix-matrix interactions. This study
      provides evidence that the provisional matrix deposited in a corneal stromal
      wound may facilitate the entry of migrating corneal fibroblasts.

PMID- 10880275
TI  - Spatiotemporal distribution of zonulae adherens and associated actin bundles in
      both epithelium and fiber cells during chicken lens development.
AB  - Zonulae adherens and associated actin bundles (ZA/AB) are believed to play a
      major role in epithelial folding and invagination during morphogenesis of neural
      tube and other vesicular structures. The lens morphogenesis is associated with
      the formation of the lens vesicle in which ZA/AB would be needed during the
      formation process. However, the existence of ZA/AB in the lens has never been
      established. In this study we report for the first time the existence of ZA/AB in
      both lens epithelium and fiber cells during embryonic development of chicken lens
      from E4 to E20. Light microscopy revealed contacts between the lens epithelium
      and primary fiber cells, and between the lens epithelium and secondary fiber
      cells at E4 and E11, respectively. Thin-section electron microscopy consistently
      revealed ZA/AB near both the apical ends of lens epithelial cells and primary
      fiber cells at E4. This arrangement manifests as a parallel pair of belt-like
      ZA/AB along the epithelium-fiber interface. In semi-tangential sections, a
      continuous belt-like ZA/AB was also evidenced in individual epithelial cells and
      fiber cells. Furthermore, the same ZA/AB arrangement was observed near both the
      apical ends of epithelial cells and secondary fiber cells at E11. Besides ZA/AB,
      macular-type fasciae adherens were distributed regularly between epithelial
      cells, between primary fibers, between secondary fibers, and between epithelium
      and both primary and secondary fibers. Immunofluorescence strongly and
      preferentially labeled N-cadherin at both the apical ends of lens epithelium and
      primary or secondary fibers at the corresponding ages, suggesting a direct
      association with the zonulae adherens. Also punctate N-cadherin labeling was
      commonly seen along various regions of primary and secondary fiber cells at
      different ages, and to a larger extent in the mature fibers of older lenses. This
      study suggests that: (1) ZA/AB located at the apices of lens epithelial cells may
      play a crucial role in the early stages of lens morphogenesis (e.g. lens vesicle
      formation); (2) ZA/AB of primary and secondary fiber cells originate from the
      epithelial cells during their elongation and differentiation; (3) owing to the
      restricted distribution of ZA/AB, abundant fasciae adherens are needed to
      maintain the structural stability of the epithelium and fiber cells during
      development and maturation; and (4) N-cadherin is the principle adhesion protein
      for both the zonulae adherens and fasciae adherens in the lens.

PMID- 10880276
TI  - Studies of lipoxygenases in the epithelium of cultured bovine cornea using an air
      interface model.
AB  - Epithelial lipoxygenases of bovine cornea were investigated in organ culture
      models. Subcellular fractions of the epithelium were incubated with(14)C-labelled
      arachidonate and the metabolites were analysed. Bovine corneal epithelial cells
      contain 15-lipoxygenase type 2 and 12-lipoxygenases of the leukocyte and the
      platelet types. The 15-lipoxygenase activity was prominent in the cytosolic
      fraction. Twelve- and 15-lipoxygenases occurred in the microsomal fraction, where
      the 15-lipoxygenase activity appeared to be favoured by low protein levels. The
      lipoxygenase activities strongly declined within 24 hr when the cornea was
      covered with cell culture medium, but were maintained with high activity in an
      air interface organ culture model for at least 72 hr. Cultured corneas were
      studied in pairs in the air interface model under influence of inflammatory
      stimuli. The epithelial 15- and 12-lipoxygenase activities were only slightly
      augmented by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (10 microM, 8
      72 hr), and remained unchanged after treatment with lipopolysaccharide (1-100
      microgram ml(-1), 8-72 hr) or UV irradiation (301 nm, 0.17 J cm(-2); 8-24 hr). In
      some experiments, 5-lipoxygenase activity was detectable, as judged from liquid
      chromatography-mass spectrometry and chiral chromatography. Reverse transcription
      polymerase chain reaction and Northern blot analysis were therefore used to
      identify mRNA of 5-lipoxygenase and related enzymes in bovine epithelium. 5
      Lipoxygenase was detected as an amplicon of 695 bp, which had 91% nucleotide
      sequence identity with human 5-lipoxygenase and by Northern blot as a 3.0 kb
      mRNA. Leukotriene A(4)hydrolase was detected with the same techniques. The amino
      acid sequence of a 612 bp fragment was 90% identical with human leukotriene
      A(4)hydrolase and the size of the mRNA was 2.7 kb. The two enzymes were also
      detected in human corneal epithelium by reverse transcription-polymerase chain
      reaction.

PMID- 10880277
TI  - The functions of exogenous and endogenous laminin-5 on corneal epithelial cells.
AB  - Recent evidence suggests that the basement membrane not only separates basal
      cells from Bowman's layer, but also has a crucial role in the proliferation,
      differentiation and migration of corneal epithelial cells. The basement membrane
      is composed of a mixture of matrix components including collagens, laminins and
      heparan sulfate proteoglycans. In these extracellular matrixes, laminin is a
      major component of the basement membrane. Of 11 laminin isoformes, laminin-5 is a
      variant, composed of three nonidentical subunits alpha3, beta3, gamma2 and is a
      major component of the corneal basement membrane. However, little is known about
      the interactions of laminin-5 with corneal epithelial cells. In this study, we
      investigated the functions of laminin-5 on SV-40 transfected human corneal
      epithelial cells (HCE cells). We also revealed different functions between
      exogenous and endogenous laminin-5 on HCE cells. Laminin-5 is synthesized
      initially as a 490 kDa molecule that undergoes specific processing to cleavaged
      isoforms after being secreted. The alpha3 subunit is processed from 200-190 kDa
      to 160 kDa/145 kDa. The gamma2 subunit is processed from 150 kDa to 105 kDa/80
      kDa. The beta3 subunit (140 kDa) is not processed. Exogenously added laminin-5
      (soluble form) in this study was purified from a serum-free, conditioned medium
      of a human gastric carcinoma cell line STKM-I. This soluble laminin is a
      processed isoform containing alpha3 (160 kDa), beta3 (140 kDa) and gamma2 (105
      kDa) chains. On the other hand, immunocytochemical analysis showed that HCE cells
      themselves secreted laminin-5 endogenously. Western blotting analysis revealed
      that HCE cells initially produced unprocessed isoform containing 190 kDa alpha3,
      140 kDa beta3 and 150 kDa gamma2 chains and that after being secreted, the alpha3
      chain was processed to 160 kDa/145 kDa and the gamma2 chain was processed to 105
      kDa. Initially we investigated the functions of exogenous (processed) laminin-5
      on HCE cells. Exogenously added laminin-5 strongly promoted cell adhesion via
      alpha3beta1 integrin, cell spreading, assembly of hemidesmosomes and mildly
      inhibited cell migration. Next we estimated the effect of endogenous
      (unprocessed) laminin-5 on HCE cells. Using an anti laminin-5 monoclonal antibody
      (mAb) or anti integrin alpha3beta1 mAbs, the blocking of the interaction between
      endogenously secreted laminin-5 and HCE cells caused strong inhibition of cell
      migration. Integrin alpha3beta1 and alpha6beta4 were expressed in HCE cells.
      These integrins are receptors of laminin-5. But, anti integrin alpha6beta4 mAbs
      did not have any blocking ability against cell migration. These results indicated
      that endogenous (unprocessed) laminin-5 has a crucial role in cell migration on
      HCE cells via alpha3beta1 integrin. In conclusion, structural differences between
      exogenous (processed) and endogenous (unprocessed) laminin-5 regulated their
      functions on HCE cells. Exogenously added laminin-5 strongly promoted cell
      adhesion, cell spreading and assembly of hemidesmosomes. Endogenously secreted
      laminin-5 had a crucial role in cell migration. In the future, processed soluble
      laminin-5 could be a useful drug for the prevention of recurrent corneal erosion,
      and unprocessed soluble laminin-5 could be applied for the treatment of prolonged
      corneal epithelial defects.

PMID- 10880278
TI  - Expression and characterization of SPARC in human lens and in the aqueous and
      vitreous humors.
AB  - SPARC (secreted protein, acidic and rich in cysteine) is a matricellular
      glycoprotein that regulates morphogenesis, cellular proliferation, and
      differentiation. SPARC is a critical factor in the development and maintenance of
      lens transparency in mice. SPARC-null mice develop lenticular opacity at an early
      age that progresses gradually to mature cataract. Despite the high level of
      homology between the mouse and human genes, little is known about SPARC in the
      human lens. We have studied the expression of SPARC protein in human lens and
      surrounding ocular tissues from normal human donors (60-70 years old).
      Immunohistochemical and immunoblot analyses were conducted on lens, aqueous
      humor, vitreous, ciliary epithelium, pigment epithelium, cornea and retina. The
      epithelia and capsule of the lens contained SPARC, whereas the cortical and
      nuclear fibers did not. In contrast, the aqueous humor and vitreous, which
      provide nutrients to the lens and regulate its development and function,
      contained significant amounts of SPARC. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of extracts of various ocular tissues revealed bands of 43 and 29
      kD after disulfide bond reduction that were reactive with anti-SPARC IgG. Despite
      the presence of protease inhibitors during sample preparation, we observed
      cleavage of intact SPARC to a 29 kD fragment, a peptide reported in other tissues
      and attributed to endogenous proteolysis. In addition, bands of molecular mass
      150 and 200 kD were present that appeared to be disulfide-bonded complexes of
      SPARC monomers. Human cornea, ciliary epithelium, pigment epithelium and retina
      also contained SPARC. The presence of SPARC in the aqueous humor and vitreous, as
      well as in the lens, indicates a functional importance of SPARC in adult human
      eye as well as in lens development.

PMID- 10880279
TI  - Re-orientation and faster, directed migration of lens epithelial cells in a
      physiological electric field.
AB  - The vertebrate lens drives current through itself in a pattern which concentrates
      current efflux at the lens equator. Lens epithelial cells (LECs) move into this
      region where they change shape and differentiate into lens fibre cells. The
      mechanisms underpinning these cell behaviors are unclear. We have attempted to
      mimic, in isolation, the effects which such electrical signals have on LEC
      behaviors, by culturing LECs in a physiological DC electric field (EF) similar to
      that in lens. Primary human (PHLECs), primary bovine (PBLECs) and a transformed
      human cell line (THLECs) all changed shape to lie perpendicular to the EF, the
      same orientation which LECs adopt with respect to the equatorial EF as they
      differentiate into lens fibre cells. Exposure to an EF also significantly
      increased the migration rate of all three LEC types. All three LECs also showed
      directed cell migration although, curiously, different cell types moved in
      different directions. PBLECs and THLECs showed voltage-dependent, anode-directed
      migration, with a response threshold between 100-150 mV mm(-1)and 25-50 mV mm(
      1), respectively. Small sheets of THLECs also migrated anodally. By contrast
      PHLECs migrated cathodally with a response threshold below 100 mV mm(-1).
      Reversing the polarity reversed the migration direction for each cell type. These
      observations raise three possibilities: (1) that small electric field may be one
      of the cues regulating lens epithelial cell behaviors in vivo; (2) that altering
      the in vivo electric field by lens replacement may contribute to the aberrant
      migration of epithelial cells in conditions such as posterior capsule
      opacification and (3) that applying electric fields may be one way of controlling
      aberrant lens epithelial cell behaviors.

PMID- 10880280
TI  - Overexpression of protein kinase Cgamma inhibits gap junctional intercellular
      communication in the lens epithelial cells.

PMID- 10880281
TI  - Lens sphingomyelinases.

PMID- 10880282
TI  - Efficacy of gabapentin as adjunctive therapy in a large, multicenter study. The
      Steps Study Group.
AB  - The objective of this study was to determine the efficacy of gabapentin as
      adjunctive therapy in doses required to achieve the most effective seizure
      control. There were 2016 patients with partial seizures requiring adjunctive
      therapy who received gabapentin at doses up to 3600 mg/day in this open-label,
      multicenter, 16-week study. Of the 1055 patients evaluable for efficacy, 573
      received gabapentin < or =1800 mg/day and 482 received > 1800 mg/day as the
      highest dose received. For the overall efficacy evaluable population, the
      percentage of patients achieving at least a 50% reduction in seizure frequency
      was 76.0%; 46.4% of the patients were seizure free. Patients whose highest
      gabapentin dose did not require > 1800 mg/day had, at baseline, fewer seizures
      and were receiving fewer concomitant antiepileptic drugs (AEDs) at baseline than
      those patients requiring > 1800 mg/day. This suggests that patients requiring
      higher doses of gabapentin were more refractory to drug treatment at the start of
      the study. Gabapentin was well tolerated at all doses in this study. The results
      of the study demonstrate that gabapentin is effective as adjunctive therapy in
      patients with partial seizures whose seizures are inadequately controlled by
      traditional AEDs.

PMID- 10880283
TI  - Psychiatric symptoms after therapy with new antiepileptic drugs:
      psychopathological and seizure related variables.
AB  - The purpose of this paper is to understand the association between antiepileptic
      drugs (AEDs), patient characteristics, changes in seizure pattern and emergent
      psychiatric disorder, i.e. psychosis or affective disorder. To this end we
      carried out a retrospective casenote study on 89 patients who developed
      psychiatric symptoms during treatment with topiramate, vigabatrin or tiagabine.
      The psychiatric problem was either an affective or a psychotic disorder (not
      including affective psychoses). It was discovered that 99% of the patients
      suffered from complex partial seizures with or without secondary generalization.
      More than half were on polytherapy with two or more other AEDs. Nearly two-thirds
      had a previous psychiatric history. There was a strong association between the
      type of previous psychiatric illness and the type of emerging psychiatric
      problem, both for psychoses and for affective disorders. Patients on vigabatrin
      had an earlier onset of epilepsy and more neurological abnormalities than those
      on topiramate. Those patients on lower doses had a shorter interval between the
      start of the AED therapy and the onset of the psychiatric problem. A seizure-free
      period was observed in more than half of the patients before they developed the
      psychiatric symptoms, and of these more were likely to develop a psychosis rather
      than an affective disorder. There seemed to be an association of suppression of
      right-sided seizures and the onset of the psychiatric problem. The conclusions
      drawn were that patients with a previous history of psychosis or affective
      disorder tended to develop the same psychiatric problem with new AEDs. Those with
      a seizure-free period before the onset of the psychiatric problem were more
      likely to develop a psychosis than an affective disorder.

PMID- 10880284
TI  - Expressed emotion in the families of young people with epilepsy.
AB  - The parents of 41 young people with epilepsy who were living in the same
      household as the patients were interviewed using the Camberwell Family Interview,
      and ratings of expressed emotion (EE) carried out according to standard criteria.
      The presence of any seizures in the 6 months prior to interview was found to be a
      predictor of EE (p= 0. 0017). Absolute seizure frequency, as well as presence or
      absence of seizures was also found to vary with the EE score. Fathers may exhibit
      high EE by critical comments, mothers by emotional over involvement. Although it
      is unclear whether high EE is the result of seizures, or whether high EE makes
      seizures more likely to occur, an intervention study aimed at assessing the
      effect of lowering parental EE levels on young people's seizure frequency might
      be worth pursuing.

PMID- 10880285
TI  - The impact of epilepsy on the quality of life of people with epilepsy in
      Zimbabwe: a pilot study.
AB  - Epilepsy is a common cause of psychosocial disability and has been perceived to
      have a profound impact on the social functioning of individuals with epilepsy. In
      Zimbabwe a combination of developing world economic priorities (with provision of
      social and health services for disabled people not a major goal) and culturally
      mediated perceptions of epilepsy as a non-medical and feared stigma may further
      disadvantage people with epilepsy (PWE) in this respect. In order to assess both
      the level of psychosocial functioning of individuals with epilepsy and their own
      perception of it, three groups of people were sampled: attenders at a specialized
      epilepsy clinic and members of two community-based support groups. All completed
      a brief quality-of-life questionnaire with activities of daily living added.
      Those carers present completed the same questionnaire at the time of sampling.
      The results indicated that 36 of 38 people with epilepsy sampled, and their
      carers, did not perceive themselves to have sufficient cognitive impairment to
      interfere with social functioning, work performance or relationships with other
      as assessed by a subsection of the WHO SIDAM (objective evaluation of cognitive
      performance) interview. However, an adapted activities of daily Living
      Questionnaire (ADLQ) showed that three-quarters of carers (and two-thirds of PWE)
      felt that functioning was mildly to moderately reduced, particularly in the areas
      of solving daily problems and speed of thinking. One-quarter of PWE experienced
      problems with relationships to others, just less than one-fifth of PWE reported
      more than four areas of reduced functioning. Of special interest was the fact
      that 25 (66%) reported sexual functioning as not applicable, although only four
      of these were of an age group which is not sexually active (less than 15 years
      old). In addition one-third of the central Hospital Group reported difficulties
      with using public transport, but none of the Community Support Group members,
      implying that the use of Public transport becomes an issue when it is necessary
      to travel long distances and that PWE curtail their travel but do not necessarily
      view this as a restriction. The samples chosen were from groups which, compared
      with PWE as a whole, are likely to include more disabled individuals, because
      attenders at a specialized epilepsy clinic and members of support groups self
      select for more symptomatic epilepsy and a visibility. Therefore the proportion
      of PWE perceived to have difficulties with ADL in this project is not
      representative for PWE as a whole. The implications of our study are firstly that
      there is a significant need for selected groups of PWE in Zimbabwe to receive
      attention to psychosocial abilities and secondly that there are certain specific
      areas such as sexual functioning and the use of transport which deserve special
      attention. A much more detailed inventory of neuro-psychological tests will be of
      value to plan treatment strategies for those selected by the crude screening
      instruments used in this project. An important future comparison will be a survey
      of ADL and psychosocial functioning amongst PWE in rural communities, because it
      is uncertain whether PWE in rural communities are generally more or less disabled
      than those in the city.

PMID- 10880286
TI  - Ictal and interictal SPECT findings in childhood absence epilepsy.
AB  - The purpose of this study was to investigate the informative value of single
      photon emission tomography (SPECT) in relation to the pathophysiological
      functioning of the brain during absence seizures and the origin of ictal
      discharges in idiopathic generalized epilepsies (IGEs). Six patients with
      childhood absence epilepsy (CAE) were selected for the study and two consecutive
      SPECT sessions were performed concomitant with EEG recordings revealing normal
      results and during hyperventilation (HV) studies where the ictal discharges were
      induced either alone or accompanied by clinical absence seizures. All six
      patients had ictal discharges in their EEGs during HV and two of them also had
      clinical absences. SPECT findings during HV revealed an overall increase in the
      cerebral blood flow (CBF) with significantly higher values as compared to the
      baseline data. There was no indication for any focal origin in either the
      interictal or the ictal SPECT findings. Results of the study were supportive for
      the concept of subcortical origin for the absence seizures and they were also
      promising for the diagnostic value of ictal SPECT in epileptic cases with
      undetermined origin as to whether they were localization-related or generalized.

PMID- 10880287
TI  - A study on visual evoked responses in childhood epilepsy with occipital
      paroxysms.
AB  - As some apparently idiopatic epilepsies may occasionally pose diagnostic
      difficulties in regard to their precise status of etiology, evoked potentials,
      particularly visual evoked potential (VEP), may contribute to the diagnosis of
      childhood epilepsy with occipital paroxysms (CEOP) as a subsidiary method of
      evaluation. This study includes 19 children (10 boys 52.6%; 9 girls 47.4%)
      ranging in age from 5 to 17 years (mean SD = 9.68 3.28) suffering from CEOP and a
      control group of 30 normal children, matched for chronological age and sex. Peak
      amplitudes and latencies of the P100 component for pattern-shift VEP (PVEP) and
      of major positivity for flash VEP (FVEP) are measured, respectively. The results
      from this study demonstrate that amplitude and latency values in patients with
      CEOP differs insignificantly when compared with controls. Although, non
      significantly, mean values of amplitudes for both PVEP and FVEP were higher in
      the patients than in the normal children, whereas latencies in FVEP were somewhat
      longer. There may be some tendency for the amplitudes to increase and the
      latencies to be delayed in VEPs in patients with CEOP, when an overall
      interpretation of our and similar studies are considered. In certain cases of
      diagnostic difficulty, VEP values may provide further information for the
      clinician, regarding either a symptomatic or an idiopathic nature of the
      underlying disorder.

PMID- 10880288
TI  - Seizure frequency and bilateral temporal abnormalities: a proton magnetic
      resonance spectroscopy of temporal lobe epilepsy.
AB  - Proton magnetic resonance spectroscopy ((1)H-MRS) was performed in seven healthy
      volunteers and 17 patients with temporal lobe epilepsy (TLE) to clarify the
      correlation of the severity of epilepsy with bilateral temporal changes in N
      acetylaspartate (NAA), choline-containing compounds (Cho) and creatine +
      phosphocreatine (Cr). Despite unilateral EEG focus, bilateral temporal reduction
      in NAA /(Cho + Cr) was revealed in patients with intractable seizures. The
      potential for seizure generation correlated with the NAA /(Cho + Cr) reduction
      not only on the ipsilateral side but also on the contralateral side. Proton MRS
      proved to be a useful measurement for obtaining important information about the
      neuronal changes as well as the lateralization of the epileptogenic focus in TLE
      patients.

PMID- 10880289
TI  - An estimate of the prevalence of psychogenic non-epileptic seizures.
AB  - The prevalence of psychogenic non-epileptic seizures is difficult to estimate. We
      propose an estimate based on a calculation. We used the following data, which are
      known or have been estimated, and are generally accepted. A prevalence of
      epilepsy of 0.5-1%; a proportion of intractable epilepsy of 20-30%; a percentage
      of these referred to epilepsy centers of 20-50%; and a percentage of patients
      referred to epilepsy centers that are psychogenic non-epileptic seizures: 10-20%.
      Using the low estimates, the prevalence of psychogenic non-epileptic seizures
      would be 1/50 000. Using the high estimates, the prevalence of psychogenic non
      epileptic seizures would be 1/3000. The prevalence of psychogenic non-epileptic
      seizures is somewhere between 1/50 000 and 1/3000, or 2 to 33 per 100 000, making
      it a significant neurologic condition.

PMID- 10880290
TI  - Successful re-introduction of lamotrigine after initial rash.
AB  - The aim of this study was to determine whether lamotrigine can be re-introduced
      safely and with a benefit in young people who previously had a mild rash
      associated with the first introduction of this drug. In the first 150 young
      people (5-19 years old) treated with lamotrigine in a special centre for
      epilepsy, seven developed a mild rash soon after starting the drug. In none of
      these cases was the rash severe, nor was there any mucous membrane involvement.
      The lamotrigine was stopped immediately when the rash was identified and was
      subsequently re-introduced, using a special very-low-dose-escalation regime,
      starting with 0.1 mg /day total daily dose, after periods ranging from 47 to 236
      days. It was possible to re-introduce the lamotrigine without recurrence of
      persistent rash and without any adverse effects in all seven cases. The re
      introduction of lamotrigine was associated with improvement in five of the seven
      cases. It is recommended that lamotrigine is stopped as soon as any rash
      attributable to the drug develops but it may be possible to re-introduce the drug
      after mild rash using a very-slow-dose-escalation regime, with a benefit in at
      least some cases.

PMID- 10880291
TI  - Recovery of visual field constriction following discontinuation of vigabatrin.
AB  - Epilepsy patients treated with vigabatrin may develop symptomatic or asymptomatic
      concentric visual field constriction due to GABA-associated retinal dysfunction.
      The prevalence and course of this side effect are not established yet; in
      previously reported adult patients the visual disturbances seem to be
      irreversible. We present two patients with a significant improvement of visual
      field constriction and retinal function after the discontinuation of vigabatrin.
      These findings suggest that vigabatrin-associated retinal changes are at least
      partly reversible in some patients, and that these patients may benefit
      significantly from a withdrawal of vigabatrin. Larger scale clinical studies are
      needed to identify predictive factors both for the occurrence and reversibility
      of vigabatrin-associated visual field defects.

PMID- 10880292
TI  - A comparison of four new antiepileptic medications.
AB  - In order to select a new medication for a patient with epilepsy, it would be
      helpful to have an idea of which drug might have the greatest overall chance for
      success. Since epilepsy is a chronic disorder, the long-term effectiveness and
      tolerability of the medications are very important. Here, we compared gabapentin,
      lamotrigine, topiramate and vigabatrin using Kaplan-Meier survival analysis to
      see how long patients chose to stay on each drug and if they stopped, why they
      stopped. The results seem to suggest the type of responses to be expected in a
      hospital seizure clinic.

PMID- 10880293
TI  - Do learning disability services need epilepsy specialist nurses?
AB  - Epilepsy is known to cause higher rates of morbidity and mortality than in the
      general population. It is estimated that one third of people with a learning
      disability also have epilepsy, and that their epilepsy is generally more
      difficult to control. Given these two statements and with the trend to place the
      majority of people with learning disabilities in small community homes rather
      than large medical institutions, it follows that there is a need for up-to-date
      information and education for individuals and carers in a variety of settings to
      ensure best care and quality of life is achieved. Is there a need for specialist
      epilepsy nurses to work in this field?

PMID- 10880294
TI  - Cryptogenic gelastic epilepsy of frontal lobe origin: a paediatric case report.
AB  - Gelastic (laughing) seizures are an uncommon seizure type which in most cases has
      an organic cerebral pathology and specifically a hypothalamic hamartoma. The
      interictal EEG frequently shows focal activity. This report describes a 3 1/2
      year-old boy who presented with episodes of unmotivated laughter associated with
      other epileptic symptomatology before the age of 3 years. Prolonged ambulatory
      EEG monitoring recorded electroclinical seizures starting in the right frontal
      area and spreading to the adjacent frontotemporal region. Neurological
      examination and brain magnetic resonance imaging were normal. Vigabatrin resulted
      in immediate remission of the seizures and normalization of the EEG.

PMID- 10880295
TI  - Bilateral astrocytoma involving the limbic system precipitating disabling amnesia
      and seizures.
AB  - Astrocytomas involving the limbic system are usually unilateral in nature. We
      report a very unusual case where a low-grade astrocytoma originating in the left
      temporal lobe spread to the right hippocampus through the hippocampal commissure
      to cause disabling amnesia and seizures. Some improvement in the memory deficit
      was facilitated by identification of complex partial status epilepticus. EEG
      should be performed in all patients with lesions of the limbic system and
      neuropsychological problems if ongoing seizure activity is not to be missed.

PMID- 10880296
TI  - The inheritance of neuropsychological dysfunction in twins discordant for
      schizophrenia.
AB  - While genetic influences in schizophrenia are substantial, the disorder's
      molecular genetic basis remains elusive. Progress has been hindered by lack of
      means to detect nonpenetrant carriers of the predisposing genes and by
      uncertainties concerning the extent of locus heterogeneity. One approach to
      solving this complexity is to examine the inheritance of pathophysiological
      processes mediating between genotype and disease phenotype. Here we evaluate
      whether deficits in neurocognitive functioning covary with degree of genetic
      relationship with a proband in the unaffected MZ and DZ co-twins of patients with
      schizophrenia. Twin pairs discordant for schizophrenia were recruited from a
      total population cohort and were compared with a demographically balanced sample
      of control twin pairs, on a comprehensive neuropsychological test battery. The
      following four neuropsychological functions contributed uniquely to the
      discrimination of degree of genetic loading for schizophrenia and, when combined,
      were more highly correlated within MZ pairs than within DZ pairs, in both
      discordant and control twins: spatial working memory (i.e., remembering a
      sequence of spatial locations over a brief delay), divided attention (i.e.,
      simultaneous performance of a counting and visual-search task), intrusions during
      recall of a word list (i.e., "remembering" nonlist items), and choice reaction
      time to visual targets. Together with evidence from human and animal studies of
      mediation of these functions by partially distinct brain systems, our findings
      suggest that there are multiple independently inherited dimensions of neural
      deficit in schizophrenia and encourage a search for genes contributing to
      quantitative variation in discrete aspects of disease liability. On tests of
      verbal and visual episodic memory, but not on the liability-related measures,
      patients were more impaired than their own MZ co-twins, suggesting a preferential
      impact of nongenetic influences on long-term memory systems.

PMID- 10880297
TI  - The SPCH1 region on human 7q31: genomic characterization of the critical interval
      and localization of translocations associated with speech and language disorder.
AB  - The KE family is a large three-generation pedigree in which half the members are
      affected with a severe speech and language disorder that is transmitted as an
      autosomal dominant monogenic trait. In previously published work, we localized
      the gene responsible (SPCH1) to a 5.6-cM region of 7q31 between D7S2459 and
      D7S643. In the present study, we have employed bioinformatic analyses to assemble
      a detailed BAC-/PAC-based sequence map of this interval, containing 152 sequence
      tagged sites (STSs), 20 known genes, and >7.75 Mb of completed genomic sequence.
      We screened the affected chromosome 7 from the KE family with 120 of these STSs
      (average spacing <100 kb), but we did not detect any evidence of a microdeletion.
      Novel polymorphic markers were generated from the sequence and were used to
      further localize critical recombination breakpoints in the KE family. This
      allowed refinement of the SPCH1 interval to a region between new markers 013A and
      330B, containing approximately 6.1 Mb of completed sequence. In addition, we have
      studied two unrelated patients with a similar speech and language disorder, who
      have de novo translocations involving 7q31. Fluorescence in situ hybridization
      analyses with BACs/PACs from the sequence map localized the t(5;7)(q22;q31.2)
      breakpoint in the first patient (CS) to a single clone within the newly refined
      SPCH1 interval. This clone contains the CAGH44 gene, which encodes a brain
      expressed protein containing a large polyglutamine stretch. However, we found
      that the t(2;7)(p23;q31.3) breakpoint in the second patient (BRD) resides within
      a BAC clone mapping >3.7 Mb distal to this, outside the current SPCH1 critical
      interval. Finally, we investigated the CAGH44 gene in affected individuals of the
      KE family, but we found no mutations in the currently known coding sequence.
      These studies represent further steps toward the isolation of the first gene to
      be implicated in the development of speech and language.

PMID- 10880298
TI  - Further evidence for an association of ABCR alleles with age-related macular
      degeneration. The International ABCR Screening Consortium.
AB  - Age-related macular degeneration (AMD) accounts for >50% of the registered visual
      disability among North American and Western European populations and has been
      associated both with environmental factors, such as smoking, and with genetic
      factors. Previously we have reported disease-associated variants in the ABCR
      (also called ABCA4) gene in a subset of patients affected with this complex
      disorder. We have now tested our original hypothesis, that ABCR is a dominant
      susceptibility locus for AMD, by screening 1,218 unrelated AMD patients of North
      American and Western European origin and 1,258 comparison individuals from 15
      centers in North America and Europe for the two most frequent AMD-associated
      variants found in ABCR. These two sequence changes, G1961E and D2177N, were found
      in one allele of ABCR in 40 patients ( approximately 3.4%), and in 13 control
      subjects ( approximately 0.95%). Fisher's two-sided exact test confirmed that
      these two variants are associated with AMD at a statistically significant level
      (P<.0001). The risk of AMD is elevated approximately threefold in D2177N carriers
      and approximately fivefold in G1961E carriers. The identification of a gene that
      confers risk of AMD is an important step in unraveling this complex disorder.

PMID- 10880299
TI  - Immunization against potential biological warfare agents.
AB  - The intentional release of biological agents by belligerents or terrorists is a
      possibility that has recently attracted increased attention. Law enforcement
      agencies, military planners, public health officials, and clinicians are gaining
      an increasing awareness of this potential threat. From a military perspective, an
      important component of the protective pre-exposure armamentarium against this
      threat is immunization. In addition, certain vaccines are an accepted component
      of postexposure prophylaxis against potential bioterrorist threat agents. These
      vaccines might, therefore, be used to respond to a terrorist attack against
      civilians. We review the development of vaccines against 10 of the most credible
      biological threats.

PMID- 10880300
TI  - Immunorestitution disease involving the innate and adaptive response.
AB  - Immunorestitution disease (IRD) is defined as an acute symptomatic or paradoxical
      deterioration of a (presumably) preexisting infection that is temporally related
      to the recovery of the immune system. We report the temporal sequence of events
      that led to IRD caused by Pneumocystis carinii and Aspergillus terreus in 2 human
      immunodeficiency virus (HIV)-negative patients soon after the recovery of
      adaptive and innate immunity, respectively, and we review episodes noted in the
      English-language literature that fit the definition of IRD (109 episodes in 107
      patients). The median time from the recovery of neutrophil counts or termination
      of steroid therapy to the development of IRD was 8 days in cases of pulmonary
      aspergillosis (23 episodes) and hepatosplenic candidiasis (8) and 21 days for
      viral diseases such as hepatitis B (24) and viral pneumonitis (6). For IRD due to
      mycobacteriosis (27 episodes) and cryptococcosis (4) in HIV-positive patients,
      the median interval between the initiation of highly active antiretroviral
      therapy (HAART) and the onset of IRD was 11 days; for viral infections, including
      those due to cytomegalovirus (14), hepatitis B virus (1), and hepatitis C virus
      (2), the median interval was 42 days. As an emerging clinical entity, IRD merits
      further study to optimize treatment of immunosuppressed patients.

PMID- 10880301
TI  - Streptococcal toxic shock syndrome: a physician tells the story of her survival.

PMID- 10880302
TI  - Preventing the use of biological weapons: improving response should prevention
      fail.
AB  - This article presents an overview of the nature and scope of the challenges posed
      by biological weapons, and offers ways by which the infectious diseases
      professional community might address the challenges of biological weapons and
      bioterrorism.

PMID- 10880303
TI  - Epidemiology and unique aspects of aging and infectious diseases.
AB  - The elderly population will grow rapidly over the next 25 years. The majority of
      patients with serious or life-threatening infections will be old. It is
      imperative that primary care physicians and infectious diseases specialists
      become aware of and knowledgeable about the special and unique aspects of
      infections in the geriatric population.

PMID- 10880304
TI  - Methylobacterium mesophilicum infection: case report and literature review of an
      unusual opportunistic pathogen.
AB  - Methylobacterium mesophilicum is a methylotrophic, pink pigmented, gram-negative
      rod that was initially isolated from environmental sources that is being
      increasingly reported as a cause of opportunistic infections in immunocompromised
      hosts. We present the case of an immunocompromised woman who developed a central
      catheter infection with M. mesophilicum and review the other 29 cases reported in
      the literature, noting that it is frequently resistant to beta-lactam agents but
      is generally susceptible to aminoglycosides and quinolones.

PMID- 10880305
TI  - Fulminant tracheobronchial and pulmonary aspergillosis complicating imported
      Plasmodium falciparum malaria in an apparently immunocompetent woman.
AB  - We describe an unusual case of fulminant tracheobronchial and pulmonary
      aspergillosis presenting as acute respiratory distress syndrome. The patient, who
      was apparently immunocompetent, was admitted with severe Plasmodium falciparum
      malaria but died from aspergillosis.

PMID- 10880306
TI  - Fatal invasive aspergillosis complicating severe Plasmodium falciparum malaria.
AB  - We report the first 2 cases of fatal invasive aspergillosis complicating severe
      malaria. In 2 nonimmune European adults without underlying disease, death was
      directly ascribable to invasive aspergillosis. We believe that transient malaria
      induced immunosuppression allowed massive growth and overwhelming dissemination
      of preexisting Aspergillus colonization.

PMID- 10880307
TI  - Disseminated mucormycosis due to Saksenaea vasiformis in an immunocompetent
      adult.
AB  - A case of disseminated infection due to Saksenaea vasiformis in a previously well
      adult male is presented. The clinical presentation was that of septic shock with
      a distinctive rash. At postmortem, endocarditis and widespread dissemination were
      evident.

PMID- 10880308
TI  - Prevalence and clinical significance of splenomegaly in asymptomatic human
      immunodeficiency virus type 1-infected adults. Swiss HIV cohort study.
AB  - In a prospective cohort study of 70 consecutive, asymptomatic human
      immunodeficiency virus type 1 (HIV-1)-infected adults, splenomegaly was found by
      physical examination in 23% of patients and by ultrasound in 66%. Patients with
      concomitant liver disease had a higher prevalence of splenomegaly (RR 1.84;
      P<.001). During a 1-year follow-up of 66 patients, splenomegaly at enrollment was
      not predictive of any clinical event, and splenomegaly was not associated with a
      higher risk of developing AIDS during a median follow-up of 6.1 years.

PMID- 10880309
TI  - The relation between Chlamydia pneumoniae infection and abdominal aortic
      aneurysm: case-control study.
AB  - Due to recent interest in the role of Chlamydia pneumoniae as a pathogen of the
      vascular system, a case-control study was conducted to investigate the
      association between serological evidence of infection with C. pneumoniae and the
      occurrence of abdominal aortic aneurysm. Detectable IgG antibody to C. pneumoniae
      was more common among abdominal aortic aneurysm cases than among control patients
      (adjusted odds ratio, 5.97; P = .08), as was detectable IgM antibody (10% vs. 0%;
      P = .02). These findings suggest that infection with C. pneumoniae may play a
      role in the pathogenesis of abdominal aortic aneurysm; therefore, further
      research in this area is warranted.

PMID- 10880310
TI  - Possible malignant transformation of benign lymphoepithelial parotid lesions in
      human immunodeficiency virus-infected patients: report of three cases.
AB  - Benign lymphoepithelial parotid lesions (BLL) are intraparotid pathological
      changes that are commonly thought to be an early manifestation of human
      immunodeficiency virus (HIV) infection. It is not well known whether BLL may
      undergo malignant transformation into B cell lymphoma and may therefore be a sort
      of precancerous lesion. We report 3 cases of possible malignant transformation of
      BLL in HIV-infected patients.

PMID- 10880312
TI  - Persistence of an endemic (toxigenic) isolate of Clostridium difficile in the
      environment of a general medicine ward.
AB  - The epidemiology of Clostridium difficile-associated diarrhea (CDAD) in an
      endemic setting was investigated by use of DNA typing methods to determine the
      strain identity of C. difficile isolates. Two predominant toxigenic clones were
      found in the environment and accounted for 29.8% (type 1) and 15.5% (type 2) of
      CDAD cases, respectively. In endemic settings, the environment and cross
      transmission may play a role in acquisition of CDAD.

PMID- 10880311
TI  - Peripherally inserted central catheters in patients with AIDS are associated with
      a low infection rate.
AB  - We reviewed the medical records of all human immunodeficiency virus (HIV)
      infected patients who had a peripherally inserted central catheter (PICC) placed
      during a 1-year period. Ninety-seven PICCs were inserted in 66 patients for 8337
      catheter-days. Eighty of 97 catheters were used primarily to treat
      cytomegalovirus disease. The mean time to any complication was 150 days. The
      total complication rate was 6.1 per 1000 catheter-days. The total infection rate
      was 1. 3 per 1000 catheter-days, and the serious infection rate was 0.8 per 1000
      catheter-days. The mean time to a serious infection was 310 days. The
      noninfectious complication rate was 4.6 per 1000 catheter-days. PICCs were
      associated with a low infection rate and a moderate mechanical complication rate,
      which compare favorably with historical rates seen in AIDS patients with other
      types of central venous access devices. PICCs are a reasonable alternative to
      other central venous access devices in patients with HIV or AIDS.

PMID- 10880313
TI  - Rapidly progressive necrotizing fasciitis and gangrene due to Clostridium
      difficile: case report.
AB  - A case of rapidly progressive necrotizing fascitis and gas gangrene due to
      Clostridium difficile that responded very well to surgical intervention is
      described.

PMID- 10880314
TI  - Entamoeba histolytica/Entamoeba dispar infections in human immunodeficiency virus
      infected patients in the United States.
AB  - We describe the incidence of and laboratory and clinical characteristics
      associated with Entamoeba histolytica/Entamoeba dispar infection diagnosed in
      human immunodeficiency virus (HIV)-infected persons enrolled in the Adult and
      Adolescent Spectrum of HIV Disease Project. From 1 January 1990 to 1 January 1998
      (82, 518 person-years of follow-up), 111 patients (98% men) were diagnosed with
      E. histolytica/E. dispar infection. Among HIV-infected patients in the United
      States, the incidence of diagnosed E. histolytica disease is low (13.5 cases per
      10,000 person-years [95% confidence interval, 7.7-22.2], with diagnosis most
      common in those patients exposed to HIV through male-male sex.

PMID- 10880315
TI  - Response: Entamoeba infections in human immunodeficiency virus-infected patients:
      not just a tropical problem.

PMID- 10880316
TI  - Kallikrein-kinin system activation in streptococcal toxic shock syndrome.
AB  - A retrospective analysis of 7 patients with streptococcal toxic shock revealed
      isolated prolongation of the activated partial thromboplastin time, which
      returned to normal during recovery. Levels of factor XII were reduced in 2
      patients who had single factor assays performed, consistent with activation of
      the kallikrein-kinin system. We speculate that bradykinin release following
      activation of the kallikrein-kinin system in streptococcal toxic shock may
      underlie the features of pain, capillary leaking, and severe hypotension
      characteristic of this syndrome.

PMID- 10880317
TI  - Neurological symptoms during primary human immunodeficiency virus (HIV) infection
      correlate with high levels of HIV RNA in cerebrospinal fluid.
AB  - This analysis involves 22 patients with diagnosed symptomatic human
      immunodeficiency virus (HIV) infection. Neurologic symptoms were present in 11
      patients, ranging from severe and persistent headache to clinical signs
      suggestive of meningitis. A strong correlation between neurological symptoms and
      cerebrospinal fluid (CSF) viral load was found. The mean CSF HIV ribonucleic acid
      (RNA) level was 4. 12 log for patients with neurological symptoms and 2.58 log
      for patients without neurological symptoms (P<.00001). Plasma viral load alone
      does not correlate or predict central nervous system (CNS) involvement. In our
      sample of patients, HIV RNA levels could be detected in most patients regardless
      of the presence of neurological symptoms. Moreover, early treatment including
      drugs with high levels of penetration in the CNS must be considered for patients
      with primary HIV infection.

PMID- 10880318
TI  - Mycobacterium kansasii infections in patients with cancer.
AB  - Mycobacterium kansasii was isolated from 25 patients with cancer who were cared
      for at the University of Texas M. D. Anderson Cancer Center (Houston) from
      January 1987 through December 1996. Two patients (8%) had disseminated disease,
      and 23 (92%) had pleuropulmonary isolates only. Signs and symptoms of
      mycobacterial infection at the time of diagnosis were often minimal or absent
      despite substantial radiographically evident involvement. The infections
      responded well to rifampin-based antimycobacterial regimens. M. kansasii is an
      infrequent but serious cause of pulmonary and, occasionally, disseminated disease
      in patients with cancer.

PMID- 10880320
TI  - Peritoneal coccidioidomycosis: case report and review.
AB  - Peritonitis is an unusual extrapulmonary manifestation of coccidioidomycosis.
      Peritoneal involvement often has an indolent course and may resolve
      spontaneously. Optimal management has not been defined; however, fluconazole's
      spectrum of activity, pharmacokinetic profile, and efficacy in dialysis-related
      yeast peritonitis suggest that it may be an effective treatment. To our
      knowledge, we report the first case of coccidioidal peritonitis treated with
      fluconazole and review the literature.

PMID- 10880319
TI  - Recurrent blastomycosis of the central nervous system: case report and review.
AB  - Although blastomycosis of the central nervous system (CNS) occurs in
      approximately 4% of patients with blastomycosis, recurrent CNS blastomycosis is
      very rare. We review the clinical features, treatment, and outcome of 4
      previously reported cases. We also report a case of recurrent CNS blastomycosis
      successfully treated with surgery and liposomal amphotericin B after an
      inadequate response to amphotericin B therapy. This treatment may be an alternate
      approach for management of similar cases.

PMID- 10880321
TI  - Value of quantitative serology for confirmation of Helicobacter pylori
      eradication: an 18-month follow-up study.
AB  - In this study several therapies were administered to 124 H. pylori-positive
      patients and IgG antibody titers were measured by ELISA at months 0, 2, 3, 6, 12,
      and 18 months. Serum titers of IgG antibody progressively decreased after H.
      pylori eradication; at 3 months, the area under the receiver operating
      characteristic curve for the decrease of IgG antibody titers for confirming H.
      pylori eradication was 0.99, with 100% sensitivity and 99% specificity (when the
      cutoff point was set at 3 U/mL). We conclude that a decrease in serum titers of
      IgG antibody to H. pylori relatively early after completion of therapy (1 month
      after ranitidine or bismuth therapy is completed and 2.5 months after antibiotic
      therapy is completed) can be used as a noninvasive, simple, and inexpensive
      method to confirm H. pylori eradication.

PMID- 10880322
TI  - Meningitis caused by Pseudallescheria boydii treated with voriconazole.
AB  - Meningitis caused by Pseudallescheria boydii is an uncommon infection of the CNS
      that usually has a poor prognosis and a difficult treatment. We describe a case
      of chronic meningitis caused by P. boydii in an immunocompetent host that was
      successfully treated with voriconazole, a new antifungal agent.

PMID- 10880323
TI  - Need for diagnostic screening of Herpes simplex virus in patients with
      nongonococcal urethritis.
AB  - The prevalence of various microorganisms known to cause nongonococcal urethritis,
      including herpes simplex virus (HSV), was evaluated. The findings suggest that
      HSV can be a significant etiological agent in nongonococcal urethritis (NGU) and
      that the necessary laboratory investigations should be performed for all patients
      with clinical symptoms of NGU.

PMID- 10880324
TI  - Reply

PMID- 10880325
TI  - An Escherichia coli O157:H7 outbreak?

PMID- 10880326
TI  - Aspergillus: an increasing problem in tertiary care hospitals?

PMID- 10880327
TI  - African trypanosomiasis.

PMID- 10880328
TI  - Nosocomial bloodstream infections: are positive blood cultures misleading?

PMID- 10880329
TI  - Screening for latent tuberculosis in sexually transmitted disease clinics.

PMID- 10880330
TI  - Is an isolated initial phase of a tick-borne encephalitis a common event?

PMID- 10880331
TI  - Clinically relevant Aeromonas species.

PMID- 10880332
TI  - Antiviral therapy for neurological manifestations of enterovirus 71 infection.

PMID- 10880333
TI  - Klebsiella pneumoniae necrotizing fasciitis associated with diabetes and liver
      cirrhosis.

PMID- 10880334
TI  - Handwashing-the Semmelweis lesson misunderstood?

PMID- 10880335
TI  - Association of primary Pneumocystis carinii infection and sudden infant death
      syndrome.

PMID- 10880337
TI  - Cloning and mapping of human PKIB and PKIG, and comparison of tissue expression
      patterns of three members of the protein kinase inhibitor family, including PKIA.
AB  - Two novel members of the human cAMP-dependent protein kinase inhibitor (PKI) gene
      family, PKIB and PKIG, were cloned. The deduced proteins showed 70% and 90%
      identity with mouse PKIbeta and PKIgamma respectively. Both the already
      identified pseudosubstrate site and leucine-rich nuclear export signal motifs
      were defined from the 11 PKIs of different species. The PKIB and PKIG genes were
      mapped respectively to chromosome 6q21-22.1, using a radiation hybrid GB4 panel,
      and to chromosome 20q13.12-13.13, using a Stanford G3 panel. Northern-blot
      analysis of three PKI isoforms, including the PKIA identified previously,
      revealed significant differences in their expression patterns. PKIB had two
      transcripts of 1.9 kb and 1.4 kb. The former transcript was abundant in both
      placenta and brain and the latter was expressed most abundantly in placenta,
      highly in brain, heart, liver, pancreas, moderately in kidney, skeletal muscle
      and colon, and very little in the other eight tissues tested. PKIG was widely
      expressed as a 1.5-kb transcript with the highest level in heart, hardly
      detectable in thymus and peripheral blood leucocytes and was moderately expressed
      in the other tissues, with slightly different levels. However, PKIA was
      specifically expressed as two transcripts of 3.3 kb and 1.5 kb in heart and
      skeletal muscle. The distinct expression patterns of the three PKIs suggest that
      their roles in various tissues are probably different.

PMID- 10880336
TI  - Sphingosine 1-phosphate signalling in mammalian cells.
AB  - Sphingosine 1-phosphate is formed in cells in response to diverse stimuli,
      including growth factors, cytokines, G-protein-coupled receptor agonists,
      antigen, etc. Its production is catalysed by sphingosine kinase, while
      degradation is either via cleavage to produce palmitaldehyde and
      phosphoethanolamine or by dephosphorylation. In this review we discuss the most
      recent advances in our understanding of the role of the enzymes involved in
      metabolism of this lysolipid. Sphingosine 1-phosphate can also bind to members of
      the endothelial differentiation gene (EDG) G-protein-coupled receptor family
      [namely EDG1, EDG3, EDG5 (also known as H218 or AGR16), EDG6 and EDG8] to elicit
      biological responses. These receptors are coupled differentially via G(i), G(q),
      G(12/13) and Rho to multiple effector systems, including adenylate cyclase,
      phospholipases C and D, extracellular-signal-regulated kinase, c-Jun N-terminal
      kinase, p38 mitogen-activated protein kinase and non-receptor tyrosine kinases.
      These signalling pathways are linked to transcription factor activation,
      cytoskeletal proteins, adhesion molecule expression, caspase activities, etc.
      Therefore sphingosine 1-phosphate can affect diverse biological responses,
      including mitogenesis, differentiation, migration and apoptosis, via receptor
      dependent mechanisms. Additionally, sphingosine 1-phosphate has been proposed to
      play an intracellular role, for example in Ca(2+) mobilization, activation of non
      receptor tyrosine kinases, inhibition of caspases, etc. We review the evidence
      for both intracellular and extracellular actions, and extensively discuss future
      approaches that will ultimately resolve the question of dual action. Certainly,
      sphingosine 1-phosphate will prove to be unique if it elicits both extra- and
      intra-cellular actions. Finally, we review the evidence that implicates
      sphingosine 1-phosphate in pathophysiological disease states, such as cancer,
      angiogenesis and inflammation. Thus there is a need for the development of new
      therapeutic compounds, such as receptor antagonists. However, identification of
      the most suitable targets for drug intervention requires a full understanding of
      the signalling and action profile of this lysosphingolipid. This article
      describes where the research field is in relation to achieving this aim.

PMID- 10880338
TI  - HSP43, a small heat-shock protein localized to specific cells of the vulva and
      spermatheca in the nematode Caenorhabditis elegans.
AB  - Heat-shock protein 43 (HSP43) of Caenorhabditis elegans is prominently expressed
      in the utse cell, which attaches the uterus to the hypodermis, the uv1 cells
      joining the vulva and the uterus, the spermathecal valve and junctions between
      cells of the spermathecal cage. In body-wall muscle, HSP43 forms a punctate
      pattern of circumferential lines, probably corresponding to regions where the
      hypodermis contacts the muscle cells.

PMID- 10880339
TI  - Ascorbate oxidation is a prerequisite for its transport into rat liver microsomal
      vesicles.
AB  - Oxidation and uptake of ascorbate show similar time courses in rat liver
      microsomal vesicles: a rapid burst phase is followed by a slower process.
      Inhibitors of ascorbate oxidation (proadifen, econazole or quercetin) also
      effectively decreased the uptake of ascorbate. The results show that
      dehydroascorbate is the transport form of ascorbate at the membrane of the
      endoplasmic reticulum.

PMID- 10880340
TI  - Evidence for phosphorylation and ubiquitinylation of the turnip yellow mosaic
      virus RNA-dependent RNA polymerase domain expressed in a baculovirus-insect cell
      system.
AB  - All RNA viruses known to date encode an RNA-dependent RNA polymerase (RdRp) that
      is required for replication of the viral genome. We have expressed and purified
      the turnip yellow mosaic virus (TYMV) RdRp in insect cells using a recombinant
      baculovirus, either in its native form, or fused to an hexa-histidine tag.
      Phosphorylation of the protein was demonstrated by labelling experiments in vivo,
      as well as phosphatase treatment of the purified protein in vitro. Phospho amino
      acid analysis and immunoblotting experiments identified serine and threonine
      residues as being the subject of phosphorylation. Peptide mass mapping using MS
      analysis of a protein digest revealed that phosphorylation sites are localized
      within a putative PEST sequence [a sequence rich in proline (P), glutamic acid
      (E), serine (S) and threonine (T) residues] in the N-terminal region of the
      protein. Using monoclonal antibodies specific for ubiquitin conjugates, we were
      able to demonstrate that the TYMV RdRp is conjugated to ubiquitin molecules when
      expressed in insect cells. These observations suggest that the TYMV RdRp may be
      processed selectively by the ubiquitin/proteasome degradation system upon
      phosphorylation of the PEST sequence.

PMID- 10880341
TI  - Interferons activate the p42/44 mitogen-activated protein kinase and JAK-STAT
      (Janus kinase-signal transducer and activator transcription factor) signalling
      pathways in hepatocytes: differential regulation by acute ethanol via a protein
      kinase C-dependent mechanism.
AB  - Interferons (IFNs) have been used in the treatment of viral hepatitis. However,
      their effectiveness is much reduced (<10%) in alcoholics. The mechanism
      underlying this resistance remains unknown. Here, we report that IFN-alpha/beta
      and IFN-gamma rapidly activate the JAK-STAT1 (Janus kinase-signal transducer and
      activator transcription factor 1) and p42/44 mitogen-activated protein kinase
      (p42/44 MAPK) in freshly isolated rat hepatocytes. Treatment of hepatocytes with
      25-100 mM ethanol for 30 min inhibited IFN-beta- or IFN-gamma-induced STAT1
      activation and tyrosine phosphorylation. The inhibitory effect of ethanol was not
      reversed by pretreatment with either sodium vanadate, a non-selective tyrosine
      phosphatase inhibitor, or with MG132, a specific proteasome inhibitor. This
      suggests that protein tyrosine phosphatases or the ubiquitin-proteasome pathway
      are not involved in the inhibitory action of ethanol. In contrast with the JAK
      STAT signalling pathway, acute ethanol exposure significantly potentiated IFN
      beta or IFN-gamma-induced activation of p42/44 MAPK, and caused marked activation
      of protein kinase C (PKC). Inhibition of PKC partially antagonized ethanol
      attenuation of IFN-induced STAT1 activation, suggesting that PKC may be involved.
      Taken together, these findings suggest that the ability of biologically relevant
      concentrations of ethanol (less than 100 mM) to markedly inhibit IFN-activated
      STAT1 is one of the cellular mechanisms responsible for the observed resistance
      of IFN therapy in alcoholics.

PMID- 10880342
TI  - Sp1-like activity mediates angiotensin-II-induced plasminogen-activator inhibitor
      type-1 (PAI-1) gene expression in mesangial cells.
AB  - Angiotensin II (Ang II) up-regulates plasminogen-activator inhibitor type-1 (PAI
      1) expression in mesangial cells to enhance extracellular matrix formation. The
      proximal promoter region (bp -87 to -45) of the human PAI-1 gene contains several
      potent binding sites for transcription factors [two phorbol-ester-response
      element (TRE)-like sequences; D-box (-82 to -76) and P-box (-61 to 54), and one
      Sp1 binding site-like sequence, Sp1-box 1 (-72 to -67)]. We studied this region
      to determine the transcription factor(s) that mediates Ang-II-induced
      transcriptional activation of the PAI-1 gene. Various double-stranded decoy
      oligodeoxynucleotides (ODNs) corresponding to various sequences in the proximal
      promoter region were transfected to mesangial cells to examine the effects on Ang
      II-induced PAI-1 mRNA expression. Transfection with the full-length decoy (bp -87
      to -45, D-P-ODN) markedly attenuated Ang-II-induced PAI-1 mRNA expression by up
      to 70%. Transfection with D-ODN (-87 to -71) and P-ODN (-66 to -45), which
      correspond to each of the two TRE-like sequences, did not attenuate the
      expression. Gel-shift assays using nuclear extracts prepared from Ang-II-treated
      mesangial cells and D-P-ODN showed three specific complexes. The major complex
      was supershifted by anti-Sp1 antibody. The methylation-interference experiment
      demonstrated that human recombinant Sp1 bound to the so-called GT box
      (TGGGTGGGGCT, -78 to -69), which contains the Sp1-box 1. The complex that
      migrated with anti-Sp1 antibody was enhanced in the cells treated with Ang II.
      Further, D-Sp1-ODN (-85 to -63) containing the GT box attenuated up-regulation of
      PAI-1 mRNA expression induced by Ang II to a level (68+/-9% inhibition)
      comparable to D-P-ODN, whereas ODN with four mutations in the GT box had no
      effect. Our findings suggest that binding of Sp1 or an Sp1-like transcription
      factor to the GT box in the PAI-1 promoter up-regulates PAI-1 gene transcription
      in mesangial cells stimulated with Ang II. This transcription-factor binding site
      may be targeted to control Ang-II-dependent extracellular matrix formation by
      mesangial cells.

PMID- 10880343
TI  - Tissue-specificity, functional characterization and subcellular localization of a
      rat ubiquitin-specific processing protease, UBP109, whose mRNA expression is
      developmentally regulated.
AB  - A cDNA encoding an ubiquitin-specific processing protease, UBP109, in rat
      skeletal muscle was cloned and its product was characterized. Northern analysis
      revealed that UBP109 mRNA is highly expressed in testis and spleen, compared with
      other tissues. Furthermore, in situ hybridization showed that the level of UBP109
      mRNA in liver, spinal cord and brain dramatically changed during embryonic
      development, indicating that the expression of UBP109 mRNA is developmentally
      regulated. UBP109 was expressed in Escherichia coli and purified to apparent
      homogeneity using a (125)I-labelled ubiquitin-peptide fusion as a substrate. The
      purified enzyme cleaved at the C-terminus of the ubiquitin moiety in natural and
      engineered fusions irrespective of their sizes. UBP109 also released free
      ubiquitin from poly-His-tagged penta-ubiquitin. Moreover, it released free
      ubiquitin from poly-ubiquitinated protein conjugates of rabbit reticulocytes. In
      addition, UBP109 localized to both the cytoplasm and the nucleus and, among three
      putative nuclear localization sequences, only the one located near the C-terminus
      is responsible for nuclear localization. These results suggest that UBP109 may
      play an important role in generation of free ubiquitin from its precursors and
      its recycling from poly-ubiquitinated protein conjugates, and hence in regulation
      of ubiquitin-mediated cellular processes, particularly related to embryonic
      development.

PMID- 10880344
TI  - Glutathione peroxidase-1 but not -4 is involved in the regulation of cellular 5
      lipoxygenase activity in monocytic cells.
AB  - In contrast to neutrophils or B-lymphocytes, cells of the monocytic lineage like
      rat macrophages, human peripheral blood monocytes and Mono Mac 6 cells contain a
      strong inhibitor of 5-lipoxygenase (5-LO) activity, which scavenges
      hydroperoxides and inhibits 5-LO activity in broken-cell preparations in the
      absence of exogenously added thiols. Chromatographic purification of the
      inhibitor from the human monocytic cell line Mono Mac 6 and amino acid sequence
      analysis revealed that the inhibitory factor is glutathione peroxidase-1 (GPx-1).
      In contrast to the peroxidase activity of GPx-1, 5-LO inhibition by GPx-1 was
      supported by beta-mercaptoethanol and there was no absolute requirement for
      millimolar concentrations of glutathione or dithiothreitol. These cofactor
      characteristics suggest that both activities address distinct catalytic
      properties of GPx-1. 5-LO inhibition by GPx-1 was not due to direct GPx-5-LO
      protein-protein interactions, since GPx-1 did not bind to immobilized 5-LO.
      Interestingly, 5-LO derived from granulocytes was significantly more resistant
      against GPx-1 inhibition than B-lymphocytic 5-LO, which correlates with the
      respective cellular 5-LO activities. In summary, the data suggest that, in
      addition to previously reported phospholipid hydroperoxide glutathione peroxidase
      (GPx-4), GPx-1 is an efficient inhibitor of 5-LO even at low thiol
      concentrations, and is involved in the regulation of cellular 5-LO activity in
      various cell types.

PMID- 10880345
TI  - Esterification of free fatty acids in adipocytes: a comparison between octanoate
      and oleate.
AB  - Medium-chain triacylglycerols (MCT) are present in milk, coconut oil and other
      foods, and are used therapeutically in special diets for certain disorders of
      lipid and glucose utilization. Recently, it has become apparent that MCT are not
      only oxidized in the liver, but are also present in lymph and fat tissue,
      particularly after chronic treatment. To evaluate the influence of MCT on
      metabolism in fat cells, we compared incorporation of octanoate and oleate into
      cellular triacylglycerols of 3T3-L1 adipocytes as well as their effects on
      preadipocyte differentiation. We found that less octanoate than oleate was stored
      and that more octanoate than oleate was oxidized. Octanoate was esterified to a
      greater extent at the sn-1,3 position of glyceryl carbons than at the sn-2
      position, whereas the opposite was true for oleate. Glycerol release from fat
      cells pre-treated with octanoate was also greater than from cells pre-treated
      with oleate, presumably related to the preferential release of octanoate from the
      sn-1,3 position. Octanoate was not incorporated into lipids in undifferentiated
      cells and did not induce differentiation in these cells, whereas oleate was
      readily stored and actually induced differentiation. Incorporation of octanoate
      into lipids increased as cells differentiated, but reached a maximum of about 10%
      of the total stored fatty acids. If these effects in vitro also occur in vivo,
      substitution of octanoate for oleate or other long-chain fatty acids could have
      the beneficial effect of diminishing fat-cell number and lipid content.

PMID- 10880346
TI  - Link peptide cartilage growth factor is degraded by membrane proteinases.
AB  - The peptide DHLSDNYTLDHDRAIH (Link N), cleaved from the N-terminus of the link
      protein component of cartilage proteoglycan aggregates by the action of
      stromelysin, can act as a growth factor and stimulate synthesis of proteoglycans
      and collagen in articular cartilage [McKenna, Liu, Sansom and Dean (1998)
      Arthritis Rheum. 41, 157-161]. The mechanism by which this biologically active
      peptide is degraded and inactivated was investigated using U937 monocytes as a
      model cell. Time-course experiments showed that two major proteases, an initial
      serine proteinase followed by a metalloproteinase, acted in sequence. Analysis of
      the resulting fragments showed that the serine endopeptidase cleavage was at the
      Leu(3)-Ser(4) bond to produce the peptide SDNYTLDHDRAIH. The terminal serine
      could then be removed from the resulting peptide by an aminopeptidase. A second
      metallopeptidase liberated the peptides SDNYTL or DNYTL from DHDRAIH by cleavage
      at the Leu(9)-Asp(10) bond. The DNYTL peptide intermediate was degraded too
      rapidly to allow sequencing and sequential aminopeptidase cleavages removed
      further amino acids from the N-terminus of the remaining DHDRAIH peptide. The
      identical patterns of breakdown that occurred when either whole cells or purified
      plasma membranes were used indicated that proteolysis and inactivation of Link N
      was carried out entirely by membrane-associated enzymes.

PMID- 10880347
TI  - Evidence that 12-lipoxygenase product 12-hydroxyeicosatetraenoic acid activates
      p21-activated kinase.
AB  - The effect of 12-hydroxyeicosatetraenoic acid (12-HETE), an arachidonic acid
      metabolite of 12-lipoxygenase, to activate p21(Rac/Cdc42)-activated kinase (PAK1)
      was studied in a Chinese hamster ovary fibroblast cell line overexpressing the
      rat vascular type-1a angiotensin II receptor (CHO-AT(1a)). 12-HETE (0.1 microM)
      treatment induced a time-dependent activation of PAK1, with a peak effect at 10
      min (335 +/- 16% of control; n=3, P<0.001). The stimulatory effect of 12-HETE on
      PAK1 activity was dose-dependent, with the maximal activation at 0.01 microM
      (350+/-15% of control; n=3, P<0.001). A PAK1 fragment encoding the Cdc42/Rac
      binding domain (amino acid residues 67-150 of hPAK1 termed PBD), was transfected
      into CHO-AT(1a) cells. PBD transfection markedly reduced 12-HETE-induced PAK1
      activation. Furthermore, transfection of dominant negative Cdc42 and Rac1
      inhibited 12-HETE-induced PAK1, strongly suggesting that Cdc42 and Rac1 are the
      upstream activators of 12-HETE-induced PAK1 activation. Low concentrations (1.5
      microM) of LY294002, a highly specific inhibitor of phosphoinositide 3-kinase (PI
      3K), abolished 12-HETE-induced PAK1 activation, suggesting that PI-3K activation
      is upstream of 12-HETE-induced PAK1 activation. Transfection of dominant negative
      PAK1 blocked 12-HETE-induced PAK1, cJun N-terminal kinase (JNK1) and
      extracellular-signal-regulated kinase (ERK) activity, while transfection of
      constitutively active PAK1 stimulated PAK1, JNK1 and ERK activity, suggesting
      that PAK1 is an upstream activator of 12-HETE-induced JNK1 and ERK activation in
      these cells. We conclude that 12-HETE can activate Cdc42, Rac1 and PI-3K, which
      then participate as upstream signalling molecules for PAK1 and JNK1 activation.

PMID- 10880348
TI  - Activation of protein kinase C alters p34(cdc2) phosphorylation state and kinase
      activity in early sea urchin embryos by abolishing intracellular Ca2+ transients.
AB  - The p34(cdc2) protein kinase, a universal regulator of mitosis, is controlled
      positively and negatively by phosphorylation, and by association with B-type
      mitotic cyclins. In addition, activation and inactivation of p34(cdc2) are
      induced by Ca(2+) and prevented by Ca(2+) chelators in permeabilized cells and
      cell-free systems. This suggests that intracellular Ca(2+) transients may play an
      important physiological role in the control of p34(cdc2) kinase activity. We have
      found that activators of protein kinase C can be used to block cell cycle-related
      alterations in intracellular Ca(2+) concentration ([Ca(2+)](i)) in early sea
      urchin embryos without altering the normal resting level of Ca(2+). We have used
      this finding to investigate whether [Ca(2+)](i) transients control p34(cdc2)
      kinase activity in living cells via a mechanism that involves cyclin B or the
      phosphorylation state of p34(cdc2). In the present study we show that the
      elimination of [Ca(2+)](i) transients during interphase blocks p34(cdc2)
      activation and entry into mitosis, while the elimination of mitotic [Ca(2+)](i)
      transients prevents p34(cdc2) inactivation and exit from mitosis. Moreover, we
      find that [Ca(2+)](i) transients are not required for the synthesis of cyclin B,
      its binding to p34(cdc2) or its destruction during anaphase. However, in the
      absence of interphase [Ca(2+)](i) transients p34(cdc2) does not undergo the
      tyrosine dephosphorylation that is required for activation, and in the absence of
      mitotic [Ca(2+)](i) transients p34(cdc2) does not undergo threonine
      dephosphorylation that is normally associated with inactivation. These results
      provide evidence that intracellular [Ca(2+)](i) transients trigger the
      dephosphorylation of p34(cdc2) at key regulatory sites, thereby controlling the
      timing of mitosis entry and exit.

PMID- 10880349
TI  - Identification of active-site residues in Bradyrhizobium japonicum malonamidase
      E2.
AB  - Malonamidase (MA) E2 was previously purified and characterized from
      Bradyrhizobium japonicum USDA 110. The gene encoding this enzyme has been cloned,
      sequenced and expressed in Escherichia coli. The recombinant MAE2 was purified to
      homogeneity from the transformed E. coli. The biochemical properties of the
      recombinant enzyme are essentially identical to those from wild-type B.
      japonicum. A database search showed that the MAE2 protein has a high sequence
      similarity with the common signature sequences of the amidase family. The only
      exception is that the aspartic residue in these signature sequences is replaced
      by a glutamine residue. In order to identify amino acid residues essential for
      enzyme activity, a series of site-directed mutagenesis studies and steady-state
      kinetic experiments were performed. Gln(195), Ser(199), Cys(207) and Lys(213) of
      the common signature sequences were selected for site-directed mutagenesis. Among
      the mutants, Q195D, Q195E and S199C showed less than 0.02% of the k(cat) value of
      the wild-type enzyme, and S199A, Q195L and Q195N exhibited no detectable
      catalytic activities. Mutants (K213L, K213R and K213H) obtained by replacement of
      the only conserved basic residue, Lys(213), in the signature sequences, also
      displayed significant reductions (approx. 380-fold) in k(cat) value, whereas
      C207A kept full activity. These results suggest that MAE2 may catalyse hydrolysis
      of malonamate by a novel catalytic mechanism, in which Gln(195), Ser(199) and
      Lys(213) are involved.

PMID- 10880350
TI  - NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to
      centrosomes, is complexed to protein phosphatase 1.
AB  - The cell cycle-regulated protein serine/threonine NIMA-related kinase 2 (Nek2),
      which shows a predominant localization at centrosomes, is identified as a protein
      which interacts with protein phosphatase 1 (PP1) using the yeast two-hybrid
      system. Complex formation between Nek2 and PP1 is supported by co-precipitation
      of the two proteins using transfected expression constructs of Nek2 and the
      endogenous Nek2/PP1 proteins. The sequence KVHF in the C-terminal region of Nek2,
      which conforms to the consensus PP1-binding motif, is shown to be essential for
      the interaction of Nek2 with PP1. Nek2 activity increases with
      autophosphorylation and addition of phosphatase inhibitors and decreases in the
      presence of PP1. PP1 is a substrate for Nek2 and phosphorylation of PP1gamma(1)
      on two C-terminal sites reduces its phosphatase activity. The presence of a
      ternary complex containing centrosomal Nek2-associated protein (C-Nap1), Nek2 and
      PP1 has also been demonstrated, and C-Nap1 is shown to be a substrate for both
      Nek2 and PP1 in vitro and in cell extracts. The implications of kinase
      phosphatase complex formation involving Nek2 and PP1 are discussed in terms of
      the coordination of centrosome separation with cell cycle progression.

PMID- 10880351
TI  - Kinetics and control of oxidative phosphorylation in rat liver mitochondria after
      chronic ethanol feeding.
AB  - Changes in the kinetics and regulation of oxidative phosphorylation were
      characterized in isolated rat liver mitochondria after 2 months of ethanol
      consumption. Mitochondrial energy metabolism was conceptually divided into three
      groups of reactions, either producing protonmotive force (Deltap) (the
      respiratory subsystem) or consuming it (the phosphorylation subsystem and the
      proton leak). Manifestation of ethanol-induced mitochondrial malfunctioning of
      the respiratory subsystem was observed with various substrates; the respiration
      rate in State 3 was inhibited by 27+/-4% with succinate plus amytal, by 20+/-4%
      with glutamate plus malate, and by 17+/-2% with N,N,N',N'-tetramethyl-p
      phenylenediamine/ascorbate. The inhibition of the respiratory activity correlated
      with the lower activities of cytochrome c oxidase, the bc(1) complex, and the ATP
      synthase in mitochondria of ethanol-fed rats. The block of reactions consuming
      the Deltap to produce ATP (the phosphorylating subsystem) was suppressed after 2
      months of ethanol feeding, whereas the mitochondrial proton leak was not
      affected. The contributions of Deltap supply (the respiratory subsystem) and
      Deltap demand (the phosphorylation and the proton leak) to the control of the
      respiratory flux were quantified as the control coefficients of these subsystems.
      In State 3, the distribution of control exerted by different reaction blocks over
      respiratory flux was not significantly affected by ethanol diet, despite the
      marked changes in the kinetics of individual functional units of mitochondrial
      oxidative phosphorylation. This suggests the operation of compensatory
      mechanisms, when control redistributes among the different components within the
      same subsystem.

PMID- 10880352
TI  - Isolation and characterization of casein kinase I from Dictyostelium discoideum.
AB  - In the present study, the molecular cloning and characterization of a 49-kDa form
      of casein kinase (CK)I from Dictyostelium discoideum is reported. The predicted
      amino acid sequence shares 70% identity with the catalytic domain of the
      mammalian delta and epsilon isoforms, Drosophila CKIepsilon and
      Schizosaccharomyces pombe Hhp1, and 63% identity with Hrr25, a 57-kDa form of
      yeast CK involved in DNA repair. D. discoideum CKI (DdCKI) was expressed in
      vegetative asynchronous cells as well as in differentiated cells, as detected by
      Northern-blot analysis. The level of DdCKI expression did not change during the
      cell cycle. Antibodies raised against a truncated version of the protein
      recognized a 49-kDa protein from D. discoideum extracts. Protein expression
      paralleled the pattern found for the RNA. The expression of DdCKI in Escherichia
      coli resulted in an active enzyme that autophosphorylated and phosphorylated
      casein. Immunofluorescence assays showed that DdCKI was localized in the
      cytoplasm and nuclei of Dictyostelium cells. The lack of disruptants of the CKI
      gene suggests that this protein is essential for the vegetative growth of D.
      discoideum. Overexpression of DdCKI resulted in cells with increased resistance
      to hydroxyurea, suggesting a potential role for this kinase in DNA repair.

PMID- 10880353
TI  - Hepatic intralobular mapping of fructose metabolism in the rat liver.
AB  - Detailed mapping of glucose and lactate metabolism along the radius of the
      hepatic lobule was performed in situ in rat livers perfused with 1.5 mM lactate
      before and during the addition of 5 mM fructose. The majority of fructose uptake
      occurred in the periportal region; 45% of fructose taken up in the periportal
      half of the lobular volume being converted into glucose. Periportal lactate
      uptake was markedly decreased by addition of fructose. Basal perivenous lactate
      output, which was derived from glucose synthesized periportally, was increased in
      the presence of fructose. During fructose infusion there was a small decrease in
      cell pH periportally, but acidification of up to 0.5 pH units perivenously. The
      evidence suggests that in situ the apparent direct conversion of fructose into
      lactate represents, to a substantial extent, the result of periportal conversion
      of fructose into glucose and the subsequent uptake and glycolysis to lactate in
      the perivenous zone of some of that glucose. (31)P NMR spectroscopy showed that
      the cellular concentration of phosphomonoesters changes very little periportally
      during fructose infusion, but there was an approximate twofold increase
      perivenously, presumably due to the accumulation of fructose 1-phosphate. It may
      be inferred that fructokinase activity is expressed throughout the hepatic
      lobule.

PMID- 10880354
TI  - Regulation of BAD by cAMP-dependent protein kinase is mediated via
      phosphorylation of a novel site, Ser155.
AB  - The interaction of BAD (Bcl-2/Bcl-X(L)-antagonist, causing cell death) with Bcl
      2/Bcl-X(L) is thought to neutralize the anti-apoptotic effects of the latter
      proteins, and may represent one of the mechanisms by which BAD promotes
      apoptosis. A variety of survival signals are reported to induce the
      phosphorylation of BAD at Ser(112) or Ser(136), triggering its dissociation from
      Bcl-2/Bcl-X(L). Ser(136) is thought to be phosphorylated by protein kinase B
      (PKB, also called Akt), which is activated when cells are exposed to agonists
      that stimulate phosphatidylinositol 3-kinase (PI3K). In contrast, Ser(112) is
      reported to be phosphorylated by mitogen-activated protein (MAP) kinase-activated
      protein kinase-1 (MAPKAP-K1, also called RSK) and by cAMP-dependent protein
      kinase (PKA). Here we identify Ser(155) as a third phosphorylation site on BAD.
      We find that Ser(155) is phosphorylated preferentially by PKA in vitro and is the
      only residue in BAD that becomes phosphorylated when cells are exposed to cAMP
      elevating agents. The phosphorylation of BAD at Ser(155) prevents it from binding
      to Bcl-X(L) and promotes its interaction with 14-3-3 proteins. We also provide
      further evidence that MAPKAP-K1 mediates the phosphorylation of Ser(112) in
      response to agonists that activate the classical MAP kinase pathway. However
      insulin-like growth factor 1, a potent activator of PI3K and PKB does not
      increase the phosphorylation of Ser(136) in BAD-transfected HEK-293 cells, and
      nor is the basal level of Ser(136) phosphorylation suppressed by inhibitors of
      PI3K.

PMID- 10880355
TI  - The human breast carcinoma cell line HBL-100 acquires exogenous cholesterol from
      high-density lipoprotein via CLA-1 (CD-36 and LIMPII analogous 1)-mediated
      selective cholesteryl ester uptake.
AB  - Aberrant cell proliferation is one of the hallmarks of carcinogenesis, and
      cholesterol is thought to play an important role during cell proliferation and
      cancer progression. In the present study we examined the pathways that could
      contribute to enhanced proliferation rates of HBL-100 cells in the presence of
      apolipoprotein E-depleted high-density lipoprotein subclass 3 (HDL(3)). When HBL
      100 cells were cultivated in the presence of HDL(3) (up to 200 microg/ml HDL(3)
      protein), the growth rates and cellular cholesterol content were directly related
      to the concentrations of HDL(3) in the culture medium. In principle, two pathways
      can contribute to cholesterol/cholesteryl ester (CE) uptake from HDL(3), (i)
      holoparticle- and (ii) scavenger-receptor BI (SR-BI)-mediated selective uptake of
      HDL(3)-associated CEs. Northern- and Western-blot analyses revealed the
      expression of CLA-1 (CD-36 and LIMPII analogous 1), the human homologue of the
      rodent HDL receptor SR-BI. In line with CLA-1 expression, selective uptake of
      HDL(3)-CEs exceeded HDL(3)-holoparticle uptake between 12- and 58-fold.
      Competition experiments demonstrated that CLA-1 ligands (oxidized HDL, oxidized
      and acetylated low-density lipoprotein and phosphatidylserine) inhibited
      selective HDL(3)-CE uptake. In line with the ligand-binding specificity of CLA-1,
      phosphatidylcholine did not compete for selective HDL(3)-CE uptake. Selective
      uptake was regulated by the availability of exogenous cholesterol and PMA, but
      not by adrenocorticotropic hormone. HPLC analysis revealed that a substantial
      part of HDL(3)-CE, which was taken up selectively, was subjected to intracellular
      hydrolysis. A potential candidate facilitating extralysosomal hydrolysis of
      HDL(3)-CE is hormone-sensitive lipase, an enzyme which was identified in HBL-100
      cells by Western blots. Our findings demonstrate that HBL-100 cells are able to
      acquire HDL-CEs via selective uptake. Subsequent partial hydrolysis by hormone
      sensitive lipase could provide 'free' cholesterol that is available for the
      synthesis of cellular membranes during proliferation of cancer cells.

PMID- 10880356
TI  - Novel application of S-nitrosoglutathione-Sepharose to identify proteins that are
      potential targets for S-nitrosoglutathione-induced mixed-disulphide formation.
AB  - Site-specific S-glutathionylation is emerging as a novel mechanism by which S
      nitrosoglutathione (GSNO) may modify functionally important protein thiols. Here,
      we show that GSNO-Sepharose mimicks site-specific S-glutathionylation of the
      transcription factors c-Jun and p50 by free GSNO in vitro. Both c-Jun and p50
      were found to bind to immobilized GSNO through the formation of a mixed
      disulphide, involving a conserved cysteine residue located in the DNA-binding
      domains of these transcription factors. Furthermore, we show that c-Jun, p50,
      glycogen phosphorylase b, glyceraldehyde-3-phosphate dehydrogenase, creatine
      kinase, glutaredoxin and caspase-3 can be precipitated from a mixture of purified
      thiol-containing proteins by the formation of a mixed-disulphide bond with GSNO
      Sepharose. With few exceptions, protein binding to this matrix correlated well
      with the susceptibility of the investigated proteins to undergo GSNO- but not
      diamide-induced mixed-disulphide formation in vitro. Finally, it is shown that
      covalent GSNO-Sepharose chromatography of HeLa cell nuclear extracts results in
      the enrichment of proteins which incorporate glutathione in response to GSNO
      treatment. As suggested by DNA-binding assays, this group of nuclear proteins
      include the transcription factors activator protein-1, nuclear factor-kappaB and
      cAMP-response-element-binding protein. In conclusion, we introduce GSNO-Sepharose
      as a probe for site-specific S-glutathionylation and as a novel and potentially
      useful tool to isolate and identify proteins which are candidate targets for GSNO
      induced mixed-disulphide formation.

PMID- 10880357
TI  - Effect of inhibition of glutathione synthesis on insulin action: in vivo and in
      vitro studies using buthionine sulfoximine.
AB  - Decreased cellular GSH content is a common finding in experimental and human
      diabetes, in which increased oxidative stress appears to occur. Oxidative stress
      has been suggested to play a causative role in the development of impaired
      insulin action on adipose tissue and skeletal muscle. In this study we undertook
      to investigate the potential of GSH depletion to induce insulin resistance, by
      utilizing the GSH synthesis inhibitor, L-buthionine-[S,R]-sulfoximine (BSO). GSH
      depletion (20-80% in various tissues), was achieved in vivo by treating rats for
      20 days with BSO, and in vitro (80%) by treating 3T3-L1 adipocytes with BSO for
      18 h. No demonstrable change in the GSH/GSSG ratio was observed following BSO
      treatment. GSH depletion was progressively associated with abnormal glucose
      tolerance test, which could not be attributed to impaired insulin secretion.
      Skeletal muscle insulin responsiveness was unaffected by GSH depletion, based on
      normal glucose response to exogenous insulin, 2-deoxyglucose uptake measurements
      in isolated soleus muscle, and on normal skeletal muscle expression of GLUT4
      protein. Adipocyte insulin responsiveness in vitro was assessed in 3T3-L1
      adipocytes, which displayed decreased insulin-stimulated tyrosine phosphorylation
      of insulin-receptor-substrate proteins and of the insulin receptor, but
      exaggerated protein kinase B phosphorylation. However, insulin-stimulated glucose
      uptake was unaffected by GSH depletion. In accordance, normal adipose tissue
      insulin sensitivity was observed in BSO-treated rats in vivo, as demonstrated by
      normal inhibition of circulating non-esterified fatty acid levels by endogenous
      insulin secretion. In conclusion, GSH depletion by BSO results in impaired
      glucose tolerance, but preserved adipocyte and skeletal muscle insulin
      responsiveness. This suggests that alternative oxidation-borne factors mediate
      the induction of peripheral insulin resistance by oxidative stress.

PMID- 10880358
TI  - N-arginine dibasic convertase (nardilysin) isoforms are soluble dibasic-specific
      metalloendopeptidases that localize in the cytoplasm and at the cell surface.
AB  - N-arginine (R) dibasic (NRD) convertase (nardilysin; EC 3.4.24.61), a
      metalloendopeptidase of the M16 family, specifically cleaves peptide substrates
      at the N-terminus of arginines in dibasic motifs in vitro. In rat testis, the
      enzyme localizes within the cytoplasm of spermatids and associates with
      microtubules of the manchette and axoneme. NRD1 and NRD2 convertases, two NRD
      convertase isoforms, differ by the absence (isoform 1) or presence (isoform 2) of
      a 68-amino acid insertion close to the active site. In this study, we
      overexpressed both isoforms, either by vaccinia virus infection of BSC40 cells or
      transfection of COS-7 cells. The partially purified enzymes exhibit very similar
      biochemical and enzymic properties. Microsequencing revealed that NRD convertase
      is N-terminally processed. Results of immunocytofluorescence, immunoelectron
      microscopy and subcellular fractionation studies argue in favour of a primary
      cytosolic localization of both peptidases. Although the putative signal peptide
      did not direct NRD convertase into microsomes in an in vitro translation assay,
      biotinylation experiments clearly showed the presence of both isoforms at the
      cell surface. In conclusion, although most known processing events at pairs of
      basic residues are achieved by proprotein convertases within the secretory
      pathway, NRD convertase may fulfil a similar function in the cytoplasm and/or at
      the cell surface.

PMID- 10880359
TI  - Recovery of active medium-chain-length-poly-3-hydroxyalkanoate polymerase from
      inactive inclusion bodies using ion-exchange resin.
AB  - A novel process for the purification of active medium-chain-length
      polyhydroxyalkanoate (mcl-PHA) polymerase was developed. This process is based on
      solubilization and activation of inactive polymerase inclusion bodies by
      incubation with ion-exchange resin. The mcl-PHA polymerase 1 from Pseudomonas
      oleovorans was overproduced from the Palk promoter. Most of the polymerase
      produced was sequestered in the cytoplasm as an inactive form in insoluble
      aggregates. By incubating the protein aggregates with S-Sepharose ion-exchange
      resin in the presence of dithiothreitol and glycerol, the mcl-PHA polymerase
      could be extracted in an active and soluble form with a final yield of about 5.2
      mg/g of cell dry weight. The solubilized polymerase was able to catalyse the in
      vitro synthesis of mcl-PHA without any additional cell components, suggesting its
      potential application for production of biopolymer. The procedure used here may
      be of general value in solubilizing and activating purified inactive labile
      enzymes.

PMID- 10880360
TI  - Phosphoinositide 3-kinase-dependent phosphorylation of the dual adaptor for
      phosphotyrosine and 3-phosphoinositides by the Src family of tyrosine kinase.
AB  - We recently identified a novel adaptor protein, termed dual adaptor for
      phosphotyrosine and 3-phosphoinositides (DAPP1), that possesses a Src homology
      (SH2) domain and a pleckstrin homology (PH) domain. DAPP1 exhibits a high
      affinity interaction with PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2), which bind to
      the PH domain. In the present study we show that when DAPP1 is expressed in HEK
      293 cells, the agonists insulin, insulin-like growth factor-1 and epidermal
      growth factor induce the phosphorylation of DAPP1 at Tyr(139). Treatment of cells
      with phosphoinositide 3-kinase (PI 3-kinase) inhibitors or expression of a
      dominant-negative PI 3-kinase prevent phosphorylation of DAPP1 at Tyr(139), and a
      PH-domain mutant of DAPP1, which does not interact with PtdIns(3,4,5)P(3) or
      PtdIns(3,4)P(2), is not phosphorylated at Tyr(139) following agonist stimulation
      of cells. Overexpression of a constitutively active form of PI 3-kinase induced
      the phosphorylation of DAPP1 in unstimulated cells. We demonstrated that Tyr(139)
      of DAPP1 is likely to be phosphorylated in vivo by a Src-family tyrosine kinase,
      since the specific Src-family inhibitor, PP2, but not an inactive variant of this
      drug, PP3, prevented the agonist-induced tyrosine phosphorylation of DAPP1. Src,
      Lyn and Lck tyrosine kinases phosphorylate DAPP1 at Tyr(139) in vitro at similar
      rates in the presence or absence of PtdIns(3,4,5)P(3), and overexpression of
      these kinases in HEK-293 cells induces the phosphorylation of Tyr(139). These
      findings indicate that, following activation of PI 3-kinases, PtdIns(3,4,5)P(3)
      or PtdIns(3,4)P(2) bind to DAPP1, recruiting it to the plasma membrane where it
      becomes phosphorylated at Tyr(139) by a Src-family tyrosine kinase.

PMID- 10880361
TI  - Targeting and insertion of C-terminally anchored proteins to the mitochondrial
      outer membrane is specific and saturable but does not strictly require ATP or
      molecular chaperones.
AB  - A distinct class of proteins contain a C-terminal membrane anchor and a
      cytoplasmic functional domain. A subset of these proteins is targeted to the
      mitochondrial outer membrane. Here, to probe for the involvement of a saturable
      targeting mechanism for this class of proteins, and to elucidate the roles of
      chaperone proteins and ATP, we have utilized an in vitro targeting system
      consisting of in vitro-synthesized proteins and isolated mitochondria. To
      establish the specificity of targeting we have used a closely related protein
      pair. VAMP-1A and VAMP-1B are splice variants of the vesicle-associated membrane
      protein/synaptobrevin-1 (VAMP-1) gene. In intact cells VAMP-1B is targeted to
      mitochondria whereas VAMP-1A is targeted to membranes of the secretory pathway,
      yet these isoforms differ by only five amino acids at the extreme C-terminus.
      Here we demonstrate that, in vitro, VAMP-1B is imported into both intact
      mitochondria and mitochondrial outer-membrane vesicles with a 15-fold greater
      efficiency than VAMP-1A. We generated and purified bacterially expressed fusion
      proteins consisting of the C-terminal two-thirds of VAMP-1A or -1B proteins fused
      to glutathione S-transferase (GST). Using these fusion proteins we demonstrate
      that protein targeting and insertion is saturable and specific for the VAMP-1B
      membrane anchor. To elucidate the role of cytosolic chaperones on VAMP-1B
      targeting, we also used the purified, Escherichia coli-derived fusion proteins.
      (33)P-Labelled GST-VAMP-1B(61-116), but not GST-VAMP-1A(61-118), was efficiently
      targeted to mitochondria in a chaperone-free system. Thus the information
      required for targeting is contained within the targeted protein itself and not
      the chaperone or a chaperone-protein complex, although chaperones may be required
      to maintain a transport-competent conformation. Moreover, ATP was required for
      transport only in the presence of cytosolic chaperone proteins. Therefore the ATP
      requirement of transport appears to reflect the participation of chaperones and
      not any other ATP-dependent step. These data demonstrate that targeting of C
      terminally anchored proteins to mitochondria is sequence specific and mediated by
      a saturable mechanism. Neither ATP nor chaperone proteins are strictly required
      for either specific targeting or membrane insertion.

PMID- 10880362
TI  - pH-dependence of the fast step of maltose hydrolysis catalysed by glucoamylase G1
      from Aspergillus niger.
AB  - The presteady-state kinetic parameters of the interaction ofwild-type
      glucoamylase from Aspergillus niger (EC 3.2.1.3)with maltose were obtained and
      analysed in the pH range 3-7 withintervals of 0.25 pH units. In all cases the
      following three-step reaction scheme was found to apply. [Equation: see text].
      The general result of the analysis of the presteady-state kinetics is that
      glucoamylase G1 is affected by the protonation states of three groups, with pK(a)
      values of 2.7, 4.5 and 5.7 in the free enzyme and of 2.7, 4.75 and 6.5 in the
      first enzyme-substrate complex. The protonation of the group in the enzyme
      substrate complex with a pK(a) 6.5 hadno effect on k(2) (1640 s(-1)) or k(-2)
      (20+/-4 s(-1)), but resulted in a stronger enzyme-substrate interaction, due to a
      decrease of K(1) from 40 to 6.3 mM. In other words,when the substrate is bound,
      the pK(a) of the acidgroup changes to increase the fraction of reactive enzyme.
      Since this pK(a) parallels that of the Michaelis complex, known from the pH
      dependence of k(cat), the group in question is most probably the catalytic acid
      Glu-179. Protonation of Glu-179 thus is of no importance in the second step,
      clearly indicating that this step represents a conformational change and not the
      actual hydrolysis step of the reaction. Protonation of the pK(a)=4.75 group leads
      to a small decrease in k(2) to 1090 s(-1), and also to minor changes in K(1). The
      group with pK(a)=2.7 leads toa major decrease of k(2), of which the limit may
      bezero, but shows no effect on K(1). Thus no differenceis seen between the pK(a)
      values of the free enzymeand of the first enzyme-substrate complex at low pH.

PMID- 10880363
TI  - Identification of the differential distribution patterns of mRNAs and consensus
      binding sequences for mouse DAF-16 homologues.
AB  - daf-16 is a forkhead-type transcription factor, functioning downstream of insulin
      like signals, and is known to be critical to the regulation of life span in
      Caenorhabditis elegans. Mammalian DAF-16 homologues include AFX, FKHR and FKHRL1,
      which contain a conserved forkhead domain and three putative phosphorylation
      sites for the Ser/Thr kinase Akt/protein kinase B (PKB), as well as for DAF-16.
      To assess the function of the homologues, we examined tissue distribution
      patterns of mRNAs for DAF-16 homologues in mice. In the embryos, expressions of
      AFX, FKHR and FKHRL1 mRNAs were complementary to each other and were highest in
      muscle, adipose tissue and embryonic liver. The characteristic expression pattern
      remained in the adult, except that signals of FKHRL1 became evident in more
      tissues, including the brain. In order to clarify whether each DAF-16 homologue
      had different target genes, we determined the consensus sequences for the binding
      of DAF-16 and the mouse homologues. The binding sequences for all four proteins
      shared a core sequence, TTGTTTAC, daf-16 family protein-binding element (DBE)
      binding protein. However, electrophoretic mobility shift assay showed that the
      binding affinity of DAF-16 homologues to the core sequence was stronger than that
      to the insulin-responsive element in the insulin-like growth factor binding
      protein-1 promoter region, which has been identified as a binding sequence for
      them. We identified one copy of the DBE upstream of the first exon of sod-3 by
      searching the genomic database of C. elegans. Taken together, DAF-16 homologues
      can fundamentally regulate the common target genes in insulin-responsive tissues
      and the specificity to target genes of each protein is partially determined by
      the differences in their expression patterns.

PMID- 10880364
TI  - Substrate specificity of the expressed carotenoid 3,4-desaturase from Rubrivivax
      gelatinosus reveals the detailed reaction sequence to spheroidene and
      spirilloxanthin.
AB  - Carotenoid biosynthesis in the photosynthetic bacterium Rubrivivax gelatinosus
      leads to the formation of hydroxyspheroidene and spirilloxanthin as the products
      of a branched pathway. In this study we investigated the role of the desaturase
      encoded by crtD which catalyses the introduction of C-3,4 double bonds into
      acyclic carotenoids. The desaturase was expressed in Escherichia coli, and the
      activity and the substrate specificity of the enzyme were evaluated in vitro by
      application of structurally different carotenoids. The results indicate that the
      enzyme is a 3,4-desaturase that converts 1-hydroxy carotenoids. The 3,4
      desaturation reaction can only occur with mono-1-hydroxy carotenoids at a psi-end
      group or with 1,1'-dihydroxy derivatives carrying a 3',4'-double bond. In
      addition, 1-HO-zeta-carotene could also be converted by the desaturase. Enzyme
      kinetic studies showed a substrate preference of 1-HO-neurosporene over 1-HO
      lycopene. Consequences from the biochemical data for the reaction sequence of
      hydroxyspheroidene and spirilloxanthin formation and the interconnection of both
      branches are discussed.

PMID- 10880365
TI  - Cloning and characterization of the 5' flanking region of the sialomucin
      complex/rat Muc4 gene: promoter activity in cultured cells.
AB  - Sialomucin complex (SMC/Muc4) is a heterodimeric glycoprotein complex consisting
      of a mucin subunit ascites sialoglycoprotein-1 (ASGP-1) and a transmembrane
      subunit (ASGP-2), which is aberrantly expressed on the surfaces of a variety of
      tumour cells. SMC is transcribed from a single gene, translated into a large
      polypeptide precursor, and further processed to yield the mature ASGP-1/ASGP-2
      complex. SMC has complex spatial and temporal expression patterns in the normal
      rat, suggesting that it has complex regulatory mechanisms. A crude exon/intron
      map of the 5' regions of the SMC/Muc4 gene generated from clones isolated from a
      normal rat liver genomic DNA library reveals that this gene has a small first
      exon comprising the 5' untranslated region and signal peptide, followed by a
      large intron. The second exon appears to be large, comprising the 5' unique
      region and a large part (probably all) of the tandem repeat domain. This
      structure is strikingly similar to that reported for the human MUC4 gene. Using
      PCR-based DNA walking, 2.4 kb of the 5'-flanking region of the SMC/Muc4 gene was
      cloned and characterized. Promoter-pattern searches yielded multiple motifs
      commonly found in tissue-specific promoters. Reporter constructs generated from
      this 2.4 kb fragment demonstrate promoter activity in primary rat mammary
      epithelial cells (MEC), the human colon tumour cell line HCT-116, and the human
      lung carcinoma cell line NCI-H292, but not in COS-7 cells, suggesting epithelial
      cell specificity. Deletion constructs of this sequence transfected into rat MEC
      or HCT-116 cells demonstrate greatly varying levels of activity, suggesting that
      there are positive and negative, as well as tissue-specific, regulatory elements
      in this sequence. Taken together, these data suggest that the rat SMC/Muc4
      promoter has been identified, that it is tissue- (epithelial cell-) specific, and
      that there are both positive and negative, as well as tissue-specific, regulatory
      elements in the sequence.

PMID- 10880366
TI  - Enhancement of the thermostability and hydrolytic activity of xylanase by random
      gene shuffling.
AB  - The thermostability of Streptomyces lividans xylanase B (SlxB-cat) was
      significantly increased by the replacement of its N-terminal region with the
      corresponding region from Thermomonospora fusca xylanase A (TfxA-cat) without
      observing a decrease in enzyme activity. In spite of the significant similarity
      between the amino acid sequences of the two xylanases, their thermostabilities
      are quite different. To facilitate an understanding of the contribution of
      structure to the thermostability observed, chimaeric enzymes were constructed by
      random gene shuffling and the thermostable chimaeric enzymes were selected for
      further study. A comparative study of the chimaeric and parental enzymes
      indicated that the N-terminus of TfxA-cat contributed to the observed
      thermostability. However, too many substitutions decreased both the
      thermostability and the activity of the enzyme. The mutants with the most
      desirable characteristics, Stx15 and Stx18, exhibited significant
      thermostabilities at 70 degrees C with optimum temperatures which were 20 degrees
      C higher than that of SlxB-cat and equal to that of TfxA-cat. The ability of
      these two chimaeric enzymes to produce reducing sugar from xylan was enhanced in
      comparison with the parental enzymes. These results suggest that these chimaeric
      enzymes inherit both their thermostability from TfxA-cat and their increased
      reactivity from SlxB-cat. Our study also demonstrates that random shuffling
      between a mesophilic enzyme and its thermophilic counterpart represents a facile
      approach for the improvement of the thermostability of a mesophilic enzyme.

PMID- 10880367
TI  - VEGF expression by epithelial and stromal cell compartments: resolving a
      controversy.

PMID- 10880368
TI  - Association between the molecular pathobiology of essential hypertension and
      thrombotic diseases.

PMID- 10880369
TI  - Vascular endothelial growth factor-C and its receptor VEGFR-3 in the nasal mucosa
      and in nasopharyngeal tumors.
AB  - Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are
      important regulators of blood and lymphatic vessel growth and vascular
      permeability. Both blood and lymphatic vessels of the upper respiratory tract
      play important roles in pathological conditions, such as infections and tumors.
      Here we have studied the expression of VEGF-C and its receptor VEGFR-3 in the
      upper respiratory system by Northern blot analysis and immunohistochemistry of
      human tissues, and in situ mRNA hybridization of developing mouse embryos and
      beta-galactosidase staining of mouse embryos having a LacZ marker gene in the
      VEGFR-3 gene locus. The results demonstrate expression of VEGF-C and VEGFR-3 in
      the developing and adult nasal respiratory epithelium and in the nasal vascular
      plexus, respectively. Unlike in most other tissues, in the nasal mucosa VEGFR-3
      is expressed in both blood and lymphatic vessels. Expression of VEGF-C was also
      detected in nasal and nasopharyngeal tumor islands, which were surrounded by
      VEGFR-3-positive angiogenic blood vessels. These results suggest that VEGF-C and
      VEGFR-3 have a role in the development of the nasal submucosal vascular plexus
      and in its normal function and that they are associated with angiogenesis in
      nasal and nasopharyngeal tumors.

PMID- 10880370
TI  - Bone marrow in polycythemia vera, chronic myelocytic leukemia, and myelofibrosis
      has an increased vascularity.
AB  - Several studies have emphasized the significance of neoangiogenesis for tumor
      growth and progression, but few have focused on malignant hematological
      disorders. We studied vascular density and architecture in bone marrow samples of
      patients with chronic myeloproliferative disease (MPD). Vascular structures were
      immunostained (for von Willebrand factor/FVIII-RAG, CD 31/PECAM or Ulex europeus
      I for vessels and for vascular endothelial growth factor, VEGF) in samples from
      patients with polycythemia vera (PV) (n = 7), chronic myelocytic leukemia (CML)
      (n = 9), and myelofibrosis (MF) (n = 6) when diagnosed and were compared with
      normal bone marrow specimens (n = 9). We observed that the mean (+/- SD) vessel
      count per high-power microscopy field (HPF) was 5.3 (+/- 2.1) in normal bone
      marrow, 5.9 (+/- 2.1) in PV, 10.8 (+/- 3.2) in CML, and 14.4 (+/- 5.5) in MF (P <
      0.001 for CMP and MF versus controls). Confocal microscopy, including three
      dimensional reconstructions of the blood vessel architecture, confirmed this
      increased vessel density and revealed tortuous vessel architecture and increased
      branching in the MPD, particularly in CML and MF. Furthermore, the number of VEGF
      positive bone marrow cells was increased in CML and, particularly, in MF. Numbers
      of VEGF-positive cells and vessels per HPF correlated significantly (r = 0.41; P
      = 0. 037). Thus the myeloproliferative diseases PV, CML, and MF exhibit
      neoangiogenesis that is related to diagnosis.

PMID- 10880371
TI  - Isolation and localization of type IIb Na/Pi cotransporter in the developing rat
      lung.
AB  - Differential display analysis of rat lung at different developmental stages
      identified a fragment, HG80, which appeared on embryonic day 16.5 and thereafter.
      A full-length cDNA derived from a cDNA library of newborn rat lung probed with
      HG80 was the rat counterpart of sodium-dependent phosphate transporter type IIb
      and was designated rNaPi IIb. In situ hybridization showed that rNaPi IIb was
      expressed in type II alveolar cells, suggesting a role in the synthesis of
      surfactant in the alveoli. The time-dependent changes in localization of this
      gene in the developing lung and its possible use as a type II pneumocyte marker
      are discussed.

PMID- 10880372
TI  - Enhanced expression of cyclooxygenase-2 in high grade human transitional cell
      bladder carcinomas.
AB  - Studies in human and animal models have shown that cyclooxygenase (COX)-2 is up
      regulated in several epithelial carcinomas including colon, breast, and lung. To
      elucidate the possible involvement of COX-2 in human bladder cancer we examined
      the expression of COX isoforms in benign tissue and in bladder carcinoma
      specimens. Paraffin embedded tissues from 75 patients with urothelial carcinomas
      were immunostained with specific antibodies raised against COX-1 and COX-2. COX-1
      expression was detected in smooth muscle cells in both benign and malignant
      bladders. COX-2 immunoreactivity was absent in benign tissue and in specimens
      with low-grade urothelial carcinoma (0/23). In contrast, expression of COX-2 was
      detected in malignant epithelial cells in 38% (17/47) of specimens with high
      grade urothelial carcinomas. Expression of COX-2 in high-grade bladder cancer was
      confirmed by radioactive in situ hybridization using a COX-2-selective riboprobe.
      Both immunohistochemistry and in situ hybridization showed COX-2 expression in a
      small subset of malignant cells. COX-2 mRNA was also expressed in three out of
      seven malignant urothelial cell lines. These data demonstrate elevated expression
      of COX-2 in a high percentage of high-grade bladder carcinomas, suggesting a
      possible role of COX-2 in the progression of bladder urothelial carcinoma and
      supporting its potential as a therapeutic target in human bladder carcinoma.

PMID- 10880373
TI  - Osteopontin expression correlates with clinical outcome in patients with
      mycobacterial infection.
AB  - Osteopontin (OPN) is a protein that is expressed in chronic inflammatory diseases
      including tuberculosis, and its deficiency predisposes to more severe
      mycobacterial infections in mice. However, no reports have identified altered OPN
      expression in, or correlated these alterations to, infections in humans. The data
      presented herein identify alterations in the tissue expression of OPN protein and
      describe an inverse correlation between these levels and disease progression
      after inoculation of Mycobacterium bovis bacillus Calmette-Guerin vaccine in
      humans. Patients with regional adenitis and good clinical outcomes had abundant
      OPN in infected lymph nodes. This pattern of OPN accumulation was also observed
      in patients infected by M. avium-intracellulare. In contrast, patients with
      disseminated infection and histologically ill-defined granulomas had no
      significant osteopontin accumulation in infected lymph nodes; these patients had
      either deficiencies in the interferon-gamma receptor 1 or idiopathic immune
      defects. The level of OPN protein expression was inversely correlated with
      disseminated infection and, of particular interest, with death of the patient. We
      conclude that osteopontin expression correlates with an effective immune and
      inflammatory response when humans are challenged by a mycobacterial infection and
      that osteopontin contributes to human resistance against mycobacteria.

PMID- 10880374
TI  - The role of intracellular calcium signaling in premature protease activation and
      the onset of pancreatitis.
AB  - The exocrine pancreas synthesizes and secretes large amounts of digestive
      proteases as inactive precursor zymogens. Under physiological conditions a
      variety of cellular defense mechanisms protect the pancreatic acinar cell against
      a premature and intracellular activation of these zymogens. When these defenses
      fail, pancreatic autodigestion is initiated and acute pancreatitis can develop. A
      number of experimental observations suggest that extra- as well as intracellular
      calcium concentrations play an important part in the initiation of pancreatic
      protease activation, but the intracellular signaling events that regulate this
      process are unknown. Using a model system in which we used pancreatic acini
      (freshly prepared functional units of living acinar cells), we were able to
      simulate the conditions found during experimental pancreatitis in rodents. By
      means of a cell permeant fluorescent trypsin substrate we could demonstrate in
      these acini that premature protease activation is initiated at the apical acinar
      cell pole and occurs only in the presence of secretagogue concentrations that
      exceed those required for a maximum secretory response. By combining this
      technique with fluorescence ratio imaging for the Ca(2+)-sensitive dye fura-2, we
      could further show that this protease activation is highly dependent on the
      spatial as well as the temporal distribution of the corresponding Ca(2+) release
      from stores within the same subcellular compartment and that it is not propagated
      to neighboring acinar cells.

PMID- 10880375
TI  - Distribution and phenotype of Epstein-Barr virus-infected cells in inflammatory
      bowel disease.
AB  - Little is known about Epstein-Barr virus (EBV) infection of colon mucosa,
      particularly in inflammatory bowel diseases. Crohn's disease and ulcerative
      colitis are thought to differ in T-helper lymphocyte composition and cytokine
      secretion patterns. Some of the implicated cytokines are growth factors for EBV
      infected cells. We examined colon mucosa for differences in the distribution and
      phenotype of EBV-infected cells. Colon tissues with Crohn's disease (n = 31) or
      ulcerative colitis (n = 25) and controls (n = 60) were characterized by in situ
      hybridization and immunohistology for six EBV gene products as indicators of
      latent and replicative EBV infection. The cells were additionally phenotyped by
      combined detection of the EBV transcripts and B- or T-cell antigens. B
      lymphocytes predominated as the site of latent EBV infection in the colon and
      were most numerous in ulcerative colitis. In active ulcerative colitis, EBV
      positive lymphocytes accumulated under and within the epithelium and displayed
      evidence for replicative infection. The patterns of mucosal EBV gene expression
      indicate local impairment of virus-specific T-cell responses in active ulcerative
      colitis. Detection of EBV may help to discriminate between active ulcerative
      colitis and other inflammatory bowel diseases. Colon mucosa is a potential site
      of EBV replication and may be relevant for EBV transmission.

PMID- 10880376
TI  - Gene expression profile in prion protein-deficient fibroblasts in culture.
AB  - To investigate the physiological function of the cellular isoform of prion
      protein (PrP(C)), the gene expression profile was studied by analyzing a cDNA
      expression array containing 597 clones of various functional classes in two
      distinct skin fibroblast cell lines designated SFK and SFH, established from PrP
      deficient (PrP(-)(/-)) mice and PrP(+/+) mice, respectively. The cells were
      incubated in the culture medium with or without inclusion of basic fibroblast
      growth factor (bFGF). When SFK cells were compared with SFH cells in untreated
      conditions, the expression of 15 genes, including those essential for cell
      proliferation and adhesion, was reduced, whereas the expression of 27 genes,
      including those involved in the insulin-like growth factor-I (IGF-I) signaling
      pathway, was elevated. Northern blot analysis verified a significant down
      regulation of the receptor tyrosine kinase substrate Eps8, cyclin D1, and CD44
      mRNAs, and a substantial up-regulation of phosphatidylinositol 3-kinase p85, IGF
      I, and serine protease inhibitor-2.2 mRNAs in SFK cells. The patterns of
      induction or reduction of gene expression after exposure to bFGF showed
      considerable overlap between both cell types. Furthermore, both Eps8 and CD44
      mRNA levels were reduced greatly in the brain tissues of the cerebrum isolated
      from the PrP(-)(/-) mice. These results indicate that the disruption of the PrP
      gene resulted in an aberrant regulation of a battery of genes important for cell
      proliferation, differentiation, and survival, including those located in the Ras
      and Rac signaling pathways.

PMID- 10880377
TI  - Platelet production in the pulmonary capillary bed: new ultrastructural evidence
      for an old concept.
AB  - Although there is substantial evidence indicating that platelets are released
      from megakaryocytes in the capillary bed of the lung, this concept has not been
      universally accepted because much of the evidence has been indirect. To more
      definitively substantiate that platelet production takes place in the lungs,
      megakaryocyte and platelet production was accelerated in mice by phlebotomy or by
      administration of thrombopoietin, and ultrastructural analysis was performed on
      lung specimens. Intact megakaryocytes, megakaryocyte fragments with numerous
      demarcated platelet fields, dissociating intact platelets, and denuded
      megakaryocyte nuclei were seen in the pulmonary capillaries of mice. In addition,
      some megakaryocyte nuclei exhibited the morphological counterpart of apoptosis.
      These observations provide evidence for platelet release in the capillary bed of
      the lungs during stimulated as well as reactive thrombocytosis without precluding
      observations that some "proplatelets" form in the sinusoids of the bone marrow
      before transmigration of intact megakaryocytes into the circulation.

PMID- 10880378
TI  - PECAM-1 (CD31) expression modulates bleeding time in vivo.
AB  - PECAM-1 is a 130-kd member of the Ig superfamily present on endothelial cells,
      platelets, polymorphonuclear leukocytes, monocytes, and lymphocytes. Its
      expression begins early in development and persists through adulthood. PECAM-1
      functions as an adhesion and signaling molecule between adjacent endothelial
      cells and between endothelial cells and circulating blood elements. Antibodies
      directed against PECAM-1 have been shown to affect angiogenesis, endothelial cell
      migration, and polymorphonuclear leukocyte transmigration. Furthermore, its
      dimerization is associated with the modulation of integrin affinity. Antibody
      inhibition studies suggest that PECAM-1 plays a role in modulating thrombosis;
      however, recent in vitro aggregation studies performed on platelets harvested
      from PECAM-1-deficient mice revealed no abnormalities. In this report we
      demonstrate prolonged in vivo bleeding times in PECAM-1-deficient mice. This
      abnormality was not corrected when wild-type hematopoietic precursors were
      engrafted into marrow-ablated PECAM-1-deficient mice. Furthermore, normal
      bleeding times were observed when marrow-ablated wild-type mice were engrafted
      with hematopoietic precursors harvested from PECAM-1-deficient mice. These
      studies are consistent with a role for PECAM-1 in modulating thrombosis in the
      vasculature, which is potentially mediated by endothelial cell PECAM-1
      expression.

PMID- 10880379
TI  - Molecular analysis of microdissected tumors and preneoplastic intraductal lesions
      in pancreatic carcinoma.
AB  - Little or no data exist concerning the inactivation of tumor suppressor genes in
      intraductal lesions surrounding invasive ductal pancreatic carcinomas. Using a
      novel improved primer extension and preamplification polymerase chain reaction,
      we analyzed microdissected paraffin-embedded specimens of pancreatic carcinoma (n
      = 29) and their corresponding pancreatic intraductal lesions (PIL, n = 331) for
      loss of heterozygosity (LOH) of p16(INK4), DPC4, and p53 by microsatellite
      analysis and for p53 protein by immunohistochemistry. LOH at the p16(INK4) locus
      (9p21) was found in nine of 22 informative tumors (41%), in 15 of 25 tumors (60%)
      at the DPC4 locus (18q21.1), and in 22 of 27 tumors (81%) at the p53 locus
      (17p13). Homozygous deletions of p16(INK4) and DPC4 were found in eight of 22
      (36%) and four of 25 tumors (16%), respectively. Furthermore, 24 of 29 tumors
      (83%) revealed considerable intratumoral genetic heterogeneity. In 165 of 277
      PILs (60%) having suitable DNA for microsatellite analysis, alterations in at
      least one tumor suppressor gene were found. In individual PILs, up to three
      alterations were detected, and p53 LOH occurred even in morphologically normal
      appearing ductal epithelium near the tumor. Although deletions of all three tumor
      suppressor genes were found in PILs without nuclear atypia, there was a tendency
      toward earlier LOH of p16(INK4) compared to DPC4 and p53 in these lesions. LOH in
      tumors accompanied positive p53 immunohistochemistry in 81% but only in 38% in
      PILs.

PMID- 10880380
TI  - Angiogenesis in the mouse lung.
AB  - When pulmonary arterial blood flow is obstructed in all mammals studied, there is
      a compensatory growth of the bronchial vasculature. This angiogenesis normally
      occurs through a proliferation of the systemic circulation to the
      intraparenchymal airways. It is an important pathophysiological process, not only
      in pulmonary vascular disease, but also in lung cancer, because the blood flow
      that supplies primary lung tumors arises from the systemic circulation. In the
      mouse, however, the systemic blood vessels that supply the trachea and mainstem
      bronchi do not penetrate into the intraparenchymal airways, as they do in all
      other larger species. In this study, we attempted to generate a new functional
      bronchial circulation in the mouse by permanently obstructing 40% of the
      pulmonary circulation. We quantified the systemic blood flow to the lung with
      fluorescent microspheres for 3 months after left pulmonary artery ligation.
      Results demonstrated that a substantial systemic blood flow to the lung that can
      eventually supply up to 15% of the normal pulmonary flow can be generated
      beginning 5-6 days after ligation. These new angiogenic vessels do not arise from
      the extraparenchymal bronchial circulation. Rather they enter the lung directly
      via a totally new vasculature that develops between the visceral and parietal
      pleuras, supplied by several intercostal arteries. This unique model of
      angiogenesis occurs in the absence of any hypoxic stimulus and mimics the
      vascular source of many lung tumors.

PMID- 10880381
TI  - In vivo detection of human vascular endothelial growth factor promoter activity
      in transgenic mouse skin.
AB  - We have generated transgenic mice expressing green fluorescent protein (GFP)
      driven by 2.453-kb (-2,362 to +91) of the 5'-upstream region of the human
      vascular endothelial growth factor (VEGF) promoter to monitor changes of VEGF
      gene transcription in situ. Neonatal transgenic mice exhibited GFP-derived
      fluorescence in tissues that have been previously reported to express VEGF mRNA
      expression, including lung, cartilage, and brain. In normal skin during postnatal
      development, moderate fluorescence was observed in the upper epidermis and, more
      prominently, in the outer root sheath keratinocytes of hair follicles. Strong up
      regulation of GFP fluorescence was observed in the hyperplastic epidermis of the
      wound edge at 48 hours after wounding, whereas little GFP fluorescence was
      detected in the dermis. In situ hybridization confirmed an identical expression
      pattern of VEGF mRNA in these wounds. Topical application of 12-O
      tetradecanoylphorbol-13-acetate (TPA) induced strong VEGF-GFP expression in
      suprabasal epidermis. Little or no fibroblast-derived fluorescence was seen both
      in the wound model and after TPA application. By confocal laser microscopy,
      increased GFP fluorescence was detectable in the epidermis of intact mouse ear
      skin as early as 6 hours after topical TPA treatment. Importantly, GFP
      fluorescence was also measurable in the skin of living transgenic mice. These
      results resolve the present controversy regarding the ability of VEGF-GFP
      transgenic mouse models to correctly reflect established patterns of VEGF
      expression, and show the model to be a powerful tool for the in vivo monitoring
      of VEGF gene expression.

PMID- 10880382
TI  - Angiotensin II (AT(1)) receptor blockade reduces vascular tissue factor in
      angiotensin II-induced cardiac vasculopathy.
AB  - Tissue factor (TF), a main initiator of clotting, is up-regulated in
      vasculopathy. We tested the hypothesis that chronic in vivo angiotensin (ANG) II
      receptor AT(1) receptor blockade inhibits TF expression in a model of ANG II
      induced cardiac vasculopathy. Furthermore, we explored the mechanisms by
      examining transcription factor activation and analyzing the TF promoter.
      Untreated transgenic rats overexpressing the human renin and angiotensinogen
      genes (dTGR) feature hypertension and severe left ventricular hypertrophy with
      focal areas of necrosis, and die at age 7 weeks. Plasma and cardiac ANG II was
      three- to fivefold increased compared to Sprague-Dawley rats. Chronic treatment
      with valsartan normalized blood pressure and coronary resistance completely, and
      ameliorated cardiac hypertrophy (P < 0.001). Valsartan prevented
      monocyte/macrophage infiltration, nuclear factor-kappaB (NF-kappaB) and activator
      protein-1 (AP-1) activation, and c-fos expression in dTGR hearts. NF-kappaB
      subunit p65 and TF expression was increased in the endothelium and media of
      cardiac vessels and markedly reduced by valsartan treatment. To analyze the
      mechanism of TF transcription, we then transfected human coronary artery smooth
      muscle cells and Chinese hamster ovary cells overexpressing the AT(1) receptor
      with plasmids containing the human TF promoter and the luciferase reporter gene.
      ANG II induced the full-length TF promoter in both transfected cell lines. TF
      transcription was abolished by AT(1) receptor blockade. Deletion of both AP-1 and
      NF-kappaB sites reduced ANG II-induced TF gene transcription completely, whereas
      the deletion of AP-1 sites reduced transcription. Thus, the present study clearly
      shows an aberrant TF expression in the endothelium and media in rats with ANG II
      induced vasculopathy. The beneficial effects of AT(1) receptor blockade in this
      model are mediated via the inhibition of NF-kappaB and AP-1 activation, thereby
      preventing TF expression, cardiac vasculopathy, and microinfarctions.

PMID- 10880383
TI  - Endothelin receptor subtype distribution predisposes coronary arteries to damage.
AB  - Several vasoactive drugs that lower blood pressure and increase heart rate induce
      regional cardiotoxicity in the dog, most frequently of right coronary arteries
      and right atrium. The basis for this selective damage is thought to result from
      local changes in vascular tone and blood flow. Administration of an endothelin
      receptor antagonist (ETRA, SB 209670) to dogs induced damage most frequent and
      severe in the right coronary artery and right atrium. Because site predisposition
      may correlate with distribution of vasoactive receptors, the objectives of this
      study were to map endothelin (ET) receptor distribution and density within
      regions of dog heart using both gene (mRNA) and protein expression endpoints for
      dog ET(A) and ET(B) receptors, and, additionally, correlate ET receptor subtype
      density with regional cardiac blood flow. A 10- to 15-mmHg reduction in mean
      arterial pressure with a concomitant increase in heart rate (10-20%), a six- and
      twofold increase in regional blood flow to the right and left atrium,
      respectively, and acute hemorrhage, medial necrosis, and inflammation were
      observed in the right coronary arteries and arteries of the right atrium after
      ETRA infusion for 5 days. Radioligand protein binding to quantify both ET
      receptors in normal dog heart indicated a twofold greater density of ET receptors
      in atrial regions versus ventricular regions. Importantly, ET receptor density in
      coronary arteries was markedly (about five- to sixfold) increased above that in
      atrial or ventricular tissues. ET receptor subtype characterization indicated
      ET(B) receptors were three times more prevalent in right coronary arteries
      compared to left coronary arteries and in situ hybridization confirmed
      localization of ET(B) in vascular smooth muscle. ET(A) receptor density was
      comparable in right and left coronary arteries. Quantitative real-time polymerase
      chain reaction for ET(A) and ET(B) receptor mRNA transcripts supported the site
      prevalence for message distribution. Consequently, the composite of protein and
      message expression profiles for ET(A) and ET(B) receptors indicated a
      disproportionate distribution of ET(B) receptors within right coronary artery of
      dog and this, along with functional measures of blood flow after ETRA infusion
      indicated a predisposition for exaggerated pharmacological responses and
      subsequent damage to right coronary arteries by ET and/or ETRAs.

PMID- 10880384
TI  - Overexpression of vascular endothelial growth factor (VEGF) in the retinal
      pigment epithelium leads to the development of choroidal neovascularization.
AB  - Vascular endothelial growth factor (VEGF) has been strongly implicated in the
      development of choroidal neovascularization found in age-related macular
      degeneration. Normally expressed in low levels, this study investigates whether
      the overexpression of VEGF in the retinal pigment epithelium is sufficient to
      cause choroidal neovascularization in the rat retina. A recombinant adenovirus
      vector expressing the rat VEGF(164) cDNA (AdCMV.VEGF) was constructed and
      injected into the subretinal space. The development of neovascularization was
      followed by fluorescein angiography, which indicates microvascular
      hyperpermeability of existing and/or newly forming blood vessels, and histology.
      VEGF mRNA was found to be overexpressed by retinal pigment epithelial cells and
      resulted in leaky blood vessels at 10 days postinjection, which was maintained
      for up to 31 days postinjection. By 80 days postinjection, new blood vessels had
      originated from the choriocapillaris, grown through the Bruch's membrane to the
      subretinal space, and disrupted the retinal pigment epithelium. This ultimately
      led to the formation of choroidal neovascular membranes and the death of
      overlying photoreceptor cells. By controlling the amount of virus delivered to
      the subretinal space, we were able to influence the severity and extent of the
      resulting choroidal neovascularization. These results show that even temporary
      overexpression of VEGF in retinal pigment epithelial cells is sufficient to
      induce choroidal neovascularization in the rat eye.

PMID- 10880386
TI  - Human decidua contains potent immunostimulatory CD83(+) dendritic cells.
AB  - Dendritic cells (DCs) are sentinel cells of the immune system important in
      initiating antigen-specific T-cell responses to microbial and transplantation
      antigens. DCs are particularly found in surface tissues such as skin and mucosa,
      where the organism is threatened by infectious agents. The human decidua, despite
      its proposed immunosuppressive function, hosts a variety of immunocompetent CD45
      cells such as natural killer cells, macrophages, and T cells. Here we describe
      the detection, isolation, and characterization of CD45(+), CD40(+), HLA-DR(++),
      and CD83(+) cells from human early pregnancy decidua with typical DC morphology.
      CD83(+) as well as CD1a(+) cells were found in close vicinity to endometrial
      glands, with preference to the basal layer of the decidua. In vitro, decidual
      CD83(+) cells could be enriched to approximately 30%, with the remainder of cells
      encompassing DC-bound CD3(+) T cells. Stimulation of allogeneic T cells in a
      mixed leukocyte reaction by the decidual cell fraction enriched for CD83(+)
      cells, was similar to that obtained with blood monocyte-derived DCs,
      demonstrating the potent immunostimulatory capacity of these cells. Decidual DCs
      with morphological, phenotypic, and functional characteristics of
      immunostimulatory DCs might be important mediators in the regulation of
      immunological balance between maternal and fetal tissue, leading to successful
      pregnancy.

PMID- 10880385
TI  - The tyrosine kinase inhibitor tyrphostin AG126 reduces the development of acute
      and chronic inflammation.
AB  - Protein tyrosine kinases help to regulate the expression of many genes that play
      important roles in inflammation. Here we investigate the effects of the tyrosine
      kinase inhibitor tyrphostin AG126 in two animal models of acute and chronic
      inflammation, carrageenan-induced pleurisy and collagen-induced arthritis. We
      report here that tyrphostin AG126 (given at 1, 3, or 10 mg/kg i.p. in the
      pleurisy model or 5 mg/kg i.p. every 48 hours in the arthritis model) exerts
      potent anti-inflammatory effects in animal models of acute and chronic
      inflammation in vivo. These include the inhibition of pleural exudate formation
      and mononuclear cell infiltration (pleurisy model) and the development of
      clinical signs and tissue injury (arthritis model). Furthermore, tyrphostin AG126
      reduced the staining for nitrotyrosine and poly (ADP-ribose) polymerase (by
      immunohistochemistry) and the expression of inducible nitric oxide synthase and
      cyclooxygenase-2 in the lungs of carrageenan-treated rats and in the joints from
      collagen-treated rats. Thus, we provide the first evidence that prevention of the
      activation of protein tyrosine kinases reduces the development of acute and
      chronic inflammation, and that inhibition of the activity of certain tyrosine
      kinases may represent a novel approach for the therapy of inflammation.

PMID- 10880387
TI  - CD8(+) T cells in Hodgkin's disease tumor tissue are a polyclonal population with
      limited clonal expansion but little evidence of selection by antigen.
AB  - A minor component (about 25%) of lymphocytes in Hodgkin's disease (HD) are CD8(+)
      T cells. It is unclear whether the presence of these cells reflects an antitumor
      cytotoxic response. The goal of the present study was to investigate clonal
      composition and the T cell receptor (TCR) beta repertoire of the CD8(+) T cell
      population in HD. Single CD8(+) cells were micromanipulated from frozen tissue
      sections of lymph nodes affected by primary HD and subjected to single target
      amplification of TCRbeta gene rearrangements. Sequence analysis of the V region
      genes revealed the presence of expanded CD8(+) T cell clones in all three cases
      analyzed. Most of these clonal expansions accounted for less than 10% of the
      CD8(+) T cell population. In one case, 30% of the CD8(+) T cells belonged to one
      or two clones. Comparison of V region sequences, however, did not provide
      evidence that the micromanipulated CD8(+) cells were sampled from a population
      that was selected for particular antigen specificities. No obvious biases in TCR
      Vbeta and Jbeta gene segment usage or CDR3 length distribution were found.
      Similarities of CDR3 amino acid sequences as found in selected CDR3 structures
      were rare. These results suggest that, like CD4(+) T cells, CD8(+) T cells may
      also be recruited into the tumor tissue in an antigen-nonspecific manner.

PMID- 10880389
TI  - Fibrinogen brescia: hepatic endoplasmic reticulum storage and hypofibrinogenemia
      because of a gamma284 Gly-->Arg mutation.
AB  - The proposita suffered from liver cirrhosis and biopsy showed type 1 membrane
      bound fiberglass inclusions. The hepatic inclusion bodies were weakly periodic
      acid-Schiff diastase-positive, and on immunoperoxidase staining reacted
      specifically with anti-fibrinogen antisera. Coagulation investigations revealed
      low functional and antigenic fibrinogen together with a prolonged thrombin time
      of 37 seconds (normal, 17 to 22 seconds) suggestive of a hypodysfibrinogenemia.
      DNA sequencing of all three fibrinogen genes showed a single heterozygous
      mutation of GGG (Gly)-->CGG (Arg) at codon 284 of the gamma-chain gene. However,
      examination of purified fibrinogen chains by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, reverse-phase high-performance liquid
      chromatography, ion-exchange high-performance liquid chromatography, and
      isoelectric focusing, failed to show any evidence of the mutant gamma(Br) chain
      in plasma fibrinogen. This finding was substantiated by electrospray ionization
      mass spectrometry, which showed only a normal gamma (and Bbeta) chain mass, but a
      large increase in the portion of their disialo isoforms. We speculate that
      misfolding of the variant protein causes hepatic retention and the subsequent
      hypofibrinogenemia, and that the functional defect (dysfibrinogenemia) results
      from hypersialylation of otherwise normal Bbeta and gamma chains consequent to
      the liver cirrhosis. These conclusions were supported by studies on six other
      family members with hypofibrinogenemia, and essentially normal clotting times,
      who were heterozygous for the gamma284 Gly-->Arg mutation.

PMID- 10880388
TI  - The development of bleomycin-induced pulmonary fibrosis in mice deficient for
      components of the fibrinolytic system.
AB  - Acute and chronic pulmonary diseases are characterized by impaired fibrinolytic
      activity within the lung. To determine the role of the fibrinolytic system in
      regulating the pathologies associated with lung injury, we examined the effect of
      bleomycin, an agent that induces the development of pulmonary fibrosis, in mice
      deficient for plasminogen (Pg(-)(/-)), urokinase (u-PA(-)(/-)), urokinase
      receptor (u-PAR(-)(/-)), or tissue plasminogen activator (t-PA(-)(/-)), and in
      control wild-type (WT) mice. Pg(-)(/-) and t-PA(-)(/-) mice demonstrated an
      enhanced increase in lung collagen content relative to that observed in WT mice.
      Levels in u-PA(-)(/-) and u-PAR(-)(/-) mice were similar to those in WT mice.
      Histological analysis 14 days after lung injury confirmed enhanced interstitial
      fibrosis in Pg(-)(/-), u-PA(-)(/-), and t-PA(-)(/-) mice relative to WT and u
      PAR(-)(/-) mice. Areas of pulmonary hemorrhage were observed in bleomycin-treated
      WT mice and not in Pg(-)(/-), u-PA(-)(/-), and u-PAR(-)(/-) mice or saline
      controls. Instead, extensive areas of fibrosis were present throughout the lungs
      of bleomycin-treated Pg(-)(/-) and u-PA(-)(/-) mice. A mixed phenotype
      (hemorrhage and fibrosis) was observed in t-PA(-)(/-) and Pg(+/-) mice.
      Hemosiderin-laden macrophages were abundant in the lungs of mice exhibiting
      hemorrhage and these mice were prone to an early death. Enhanced macrophage
      levels in the lungs and activation of matrix metalloelastase (MMP-12) were found
      in mice with a hemorrhage phenotype. The results of these studies indicate a role
      for the fibrinolytic system in acute lung injury and suggests that intra-alveolar
      hemorrhage is the result of basement membrane degradation through cell-mediated u
      PA activation of Pg with possible involvement of matrix metalloproteinases.
      Absence of these two components of the fibrinolytic system, either urokinase or
      plasminogen, results in accelerated fibrosis.

PMID- 10880390
TI  - Regulation of matrix metalloproteinases and their inhibitor genes in
      lipopolysaccharide-induced endotoxemia in mice.
AB  - An imbalance between matrix metalloproteinases (MMPs) and inhibitors of MMPs
      (TIMPs) may contribute to tissue destruction that is found in various
      inflammatory disorders. To determine in an in vivo experimental setting whether
      the inflammatory reaction in the course of lipopolysaccharide (LPS)-induced
      endotoxemia causes an altered balance in the MMP/TIMP system, we analyzed the
      expression of a number of MMP and TIMP genes as well as MMP enzymatic activity in
      the liver, kidney, spleen, and brain at various time points after systemic
      injection of different doses of LPS in mice. Injection of sublethal doses of LPS
      led to an organ- and time-specific pattern of up-regulation of several MMP genes
      and the TIMP-1 gene in the liver, spleen, and kidney, whereas in the brain only
      TIMP-1 was induced. Injection of a lethal dose of LPS caused similar but more
      prolonged expression of these MMP genes as well as the induction of additional
      MMP genes in all organs. In LPS-treated mice in situ hybridization revealed
      collagenase 3 gene induction in cells resembling macrophages whereas TIMP-1 RNA
      was detected predominantly in parenchymal cells. Finally, gelatin zymography
      revealed increased gelatinolytic activity in all organs after LPS treatment.
      These observations highlight a dramatic shift in favor of increased expression of
      the MMP genes over the TIMP genes during LPS-induced endotoxemia, and suggest
      that MMPs may contribute to the development of organ damage in endotoxemia.

PMID- 10880391
TI  - Antineutrophil cytoplasmic antibodies induce reactive oxygen-dependent
      dysregulation of primed neutrophil apoptosis and clearance by macrophages.
AB  - This study assessed whether anti-neutrophil cytoplasmic antibodies (ANCAs)
      interfere with the safe deletion of neutrophils by apoptosis and phagocytic
      clearance. Tumor necrosis factor (TNF)-primed neutrophils were incubated with
      normal IgG (N IgG) or ANCA IgG for up to 36 hours. Compared with N IgG, ANCAs
      accelerated constitutive apoptosis of TNF-alpha primed neutrophils, as assessed
      by morphology and confirmed by DNA laddering pattern on gel electrophoresis, and
      accelerated progression to secondary necrosis. The accelerated apoptosis induced
      by ANCA was dependent on reactive oxygen species generation, as primed
      neutrophils from patients with chronic granulomatous disease failed to show an
      effect of ANCAs on apoptosis. However, there was no change in the rate at which
      neutrophils exhibited annexin V binding, indicating that externalization of
      phosphatidylserine was not accelerated by ANCAs. Furthermore, when ANCA-treated
      primed neutrophils were interacted with human or murine peritoneal macrophages
      after 12 hours there was significantly less phagocytosis by human macrophages and
      no difference in phagocytosis by murine peritoneal-derived macrophages when
      compared with N IgG-treated controls. In conclusion, ANCAs accelerate apoptosis
      and secondary necrosis in TNF-primed neutrophils by a mechanism dependent on the
      generation of reactive oxygen species, with uncoupling of nuclear and surface
      membrane changes, resulting in a "reduced window of opportunity" for phagocytic
      recognition and engulfment before disintegration.

PMID- 10880392
TI  - Disruption of redox homeostasis in tumor necrosis factor-induced apoptosis in a
      murine hepatocyte cell line.
AB  - Tumor necrosis factor (TNF) is a mediator of the acute phase response in the
      liver and can initiate proliferation and cause cell death in hepatocytes. We
      investigated the mechanisms by which TNF causes apoptosis in hepatocytes focusing
      on the role of oxidative stress, antioxidant defenses, and mitochondrial damage.
      The studies were conducted in cultured AML12 cells, a line of differentiated
      murine hepatocytes. As is the case for hepatocytes in vivo, AML12 cells were not
      sensitive to cell death by TNF alone, but died by apoptosis when exposed to TNF
      and a small dose of actinomycin D (Act D). Morphological signs of apoptosis were
      not detected until 6 hours after the treatment and by 18 hours approximately 50%
      of the cells had died. Exposure of the cells to TNF+Act D did not block NFkappaB
      nuclear translocation, DNA binding, or its overall transactivation capacity.
      Induction of apoptosis was characterized by oxidative stress indicated by the
      loss of NAD(P)H and glutathione followed by mitochondrial damage that included
      loss of mitochondrial membrane potential, inner membrane structural damage, and
      mitochondrial condensation. These changes coincided with cytochrome C release and
      the activation of caspases-8, -9, and -3. TNF-induced apoptosis was dependent on
      glutathione levels. In cells with decreased levels of glutathione, TNF by itself
      in the absence of transcriptional blocking acted as an apoptotic agent.
      Conversely, the antioxidant alpha-lipoic acid, that protected against the loss of
      glutathione in cells exposed to TNF+Act D completely prevented mitochondrial
      damage, caspase activation, cytochrome C release, and apoptosis. The results
      demonstrate that apoptosis induced by TNF+Act D in AML12 cells involves oxidative
      injury and mitochondrial damage. As injury was regulated to a larger extent by
      the glutathione content of the cells, we suggest that the combination of TNF+Act
      D causes apoptosis because Act D blocks the transcription of genes required for
      antioxidant defenses.

PMID- 10880393
TI  - Delayed wound healing in the absence of intercellular adhesion molecule-1 or L
      selectin expression.
AB  - Inflammatory cells play a crucial role in wound healing, but the role of adhesion
      molecules including L-selectin and intercellular adhesion molecule-1 (ICAM-1) is
      not known in this process. We examined skin wound repair of excisional wounds in
      mice lacking L-selectin, ICAM-1, or both. The loss of ICAM-1 inhibited wound
      healing, keratinocyte migration from the edges of the wound toward the center,
      and granulation tissue formation. By contrast, L-selectin deficiency alone did
      not affect any of these parameters. However, the loss of both L-selectin and ICAM
      1 resulted in inhibition of keratinocyte migration and granulation tissue
      formation beyond those caused by loss of ICAM-1 alone. Treatment of platelet
      derived growth factor to the wounds normalized delayed wound healing in ICAM-1(-/
      ) mice, but not in L-selectin/ICAM-1(-/-) mice. Therefore, although ICAM-1
      contributes to wound repair to a greater extent than L-selectin, a role for L
      selectin was revealed in the absence of ICAM-1. The impaired wound repair was
      associated with reduced infiltration of neutrophils and macrophages in ICAM-1(-/
      ) and L-selectin/ICAM-1(-/-) mice. These results demonstrate a distinct role of
      ICAM-1 and L-selectin in wound healing and that the delayed wound healing in the
      absence of these molecules is likely because of decreased leukocyte accumulation
      into the wound site.

PMID- 10880394
TI  - Interleukin-1alpha is a paracrine inducer of FGF7, a key epithelial growth factor
      in benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is an extremely common disease of older men in
      which there is benign overgrowth of the prostatic transition zone, leading to
      obstruction of urine outflow. FGF7, a potent growth factor for prostatic
      epithelial cells, is increased by threefold in BPH and is correlated with
      increased epithelial proliferation in this condition. Immunohistochemistry of
      normal and hyperplastic prostate revealed that FGF7-expressing fibroblastic cells
      were present in higher numbers near the epithelial acini, implying that
      epithelial cells may express a factor that induces FGF7 expression by stromal
      cells. Conditioned medium (CM) from primary cultures of prostatic epithelial
      cells was capable of inducing a two- to sixfold increase in the expression of
      FGF7 by primary stromal cultures. Blocking experiments with neutralizing anti
      interleukin-1alpha (Il-1alpha) antibodies and IL-1Ra, an Il-1alpha receptor
      antagonist, show that this inducing activity was due to the presence of Il-1alpha
      in the epithelial CM. Analysis of normal prostatic peripheral zone and BPH tissue
      by enzyme-linked immunoabsorption assay reveal that Il-1alpha is present at
      increased levels in hyperplastic prostate and that levels of Il-1alpha correlate
      strongly with tissue FGF7 concentration in BPH. Therefore Il-1alpha is produced
      by prostatic epithelial cells and can induce FGF7, a potent epithelial growth
      factor, which can in turn lead to further epithelial growth and increased Il
      1alpha secretion, thus establishing a double paracrine loop that is functionally
      equivalent to an autocrine growth loop. This double paracrine loop may play a key
      role in the abnormal proliferation of the transition zone, which is critical to
      the pathogenesis of BPH.

PMID- 10880395
TI  - Recurrent genetic aberrations in thymoma and thymic carcinoma.
AB  - Apart from single reported aberrant karyotypes, genetic alterations in thymic
      epithelial neoplasms have not been investigated so far. In this study, 12 World
      Health Organization classification type A thymomas (medullary thymomas), 16 type
      B3 thymomas (well-differentiated thymic carcinomas), and nine type C thymomas,
      all of them primary thymic squamous cell carcinomas, were analyzed by comparative
      genomic hybridization and fluorescence in situ hybridization. With the exception
      of one single case, type A thymomas did not reveal chromosomal gains or losses in
      comparative genomic hybridization. In contrast, all type B3 thymomas showed
      chromosomal imbalances, with gain of 1q, loss of chromosome 6, and loss of 13q
      occurring in 11 (69%), six (38%), and five (31%) of 16 cases, respectively. In
      primary thymic squamous cell carcinoma, the most frequent chromosomal losses were
      observed for 16q (six of nine cases, 67%), 6 (4 of 9, 44%), and 3p and 17p (three
      of nine each, 33%), whereas recurrent gains of chromosomal material were gains of
      1q (5 of 9, 56%), 17q, and 18 (three of nine each, 33%). This study shows that
      the distinct histological thymoma types A and B3 exhibit distinct genetic
      phenotypes, whereas type B3 thymoma and primary thymic squamous cell carcinoma
      partially share genetic aberrations. In addition to the possible tumorigenic
      role, the deletion in type B3 thymoma of chromosome 6, harboring the HLA locus,
      might play a role in the pathogenesis of paraneoplastic autoimmunity
      characteristic of thymoma.

PMID- 10880396
TI  - Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative
      quantitative study of axonal injury in active, inactive, and remyelinated
      lesions.
AB  - Recent magnetic resonance (MR) studies of multiple sclerosis lesions indicate
      that axonal injury is a major correlate of permanent clinical deficit. In the
      present study we systematically quantified acute axonal injury, defined by
      immunoreactivity for beta-amyloid-precursor-protein in dystrophic neurites, in
      the central nervous system of 22 multiple sclerosis patients and 18 rats with
      myelin-oligodendrocyte glycoprotein (MOG)-induced chronic autoimmune
      encephalomyelitis (EAE). The highest incidence of acute axonal injury was found
      during active demyelination, which was associated with axonal damage in
      periplaque and in the normal appearing white matter of actively demyelinating
      cases. In addition, low but significant axonal injury was also observed in
      inactive demyelinated plaques. In contrast, no significant axonal damage was
      found in remyelinated shadow plaques. The patterns of axonal pathology in chronic
      active EAE were qualitatively and quantitatively similar to those found in
      multiple sclerosis. Our studies confirm previous observations of axonal
      destruction in multiple sclerosis lesions during active demyelination, but also
      indicate that ongoing axonal damage in inactive lesions may significantly
      contribute to the clinical progression of the disease. The results further
      emphasize that MOG-induced EAE may serve as a suitable model for testing axon
      protective therapies in inflammatory demyelinating conditions.

PMID- 10880397
TI  - Endocytic pathway abnormalities precede amyloid beta deposition in sporadic
      Alzheimer's disease and Down syndrome: differential effects of APOE genotype and
      presenilin mutations.
AB  - Endocytosis is critical to the function and fate of molecules important to
      Alzheimer's disease (AD) etiology, including the beta protein precursor (betaPP),
      amyloid beta (Abeta) peptide, and apolipoprotein E (ApoE). Early endosomes, a
      major site of Abeta peptide generation, are markedly enlarged within neurons in
      the Alzheimer brain, suggesting altered endocytic pathway (EP) activity. Here, we
      show that neuronal EP activation is a specific and very early response in AD. To
      evaluate endocytic activation, we used markers of internalization (rab5, rabaptin
      5) and recycling (rab4), and found that enlargement of rab5-positive early
      endosomes in the AD brain was associated with elevated levels of rab4
      immunoreactive protein and translocation of rabaptin 5 to endosomes, implying
      that both endocytic uptake and recycling are activated. These abnormalities were
      evident in pyramidal neurons of the neocortex at preclinical stages of disease
      when Alzheimer-like neuropathology, such as Abeta deposition, was restricted to
      the entorhinal region. In Down syndrome, early endosomes were significantly
      enlarged in some pyramidal neurons as early as 28 weeks of gestation, decades
      before classical AD neuropathology develops. Markers of EP activity were only
      minimally influenced by normal aging and other neurodegenerative diseases
      studied. Inheritance of the epsilon4 allele of APOE, however, accentuated early
      endosome enlargement at preclinical stages of AD. By contrast, endosomes were
      normal in size at advanced stages of familial AD caused by mutations of
      presenilin 1 or 2, indicating that altered endocytosis is not a consequence of
      Abeta deposition. These results identify EP activation as the earliest known
      intraneuronal change to occur in sporadic AD, the most common form of AD. Given
      the important role of the EP in Abeta peptide generation and ApoE function, early
      endosomal abnormalities provide a mechanistic link between EP alterations,
      genetic susceptibility factors, and Abeta generation and suggest differences that
      may be involved in Abeta generation and beta amyloidogenesis in subtypes of AD.

PMID- 10880398
TI  - Nestin expression in embryonic and adult human teeth under normal and
      pathological conditions.
AB  - Nestin is an intermediate filament most related to neurofilaments and expressed
      predominantly in the developing nervous system and muscles. In the present study
      we examined the in vivo distribution of nestin in human teeth during embryonic
      development and in permanent teeth under normal and pathological conditions. The
      results show that nestin is first expressed at the bell stage and that its
      distribution is restricted in pulpal cells located at the cusp area of the fetal
      teeth. In young permanent teeth, nestin is found only in functional odontoblasts,
      which produce the hard tissue matrix of dentin. Expression is progressively down
      regulated and nestin is absent from older permanent teeth. In carious and injured
      teeth, nestin expression is up-regulated in a selective manner in odontoblasts
      surrounding the injury site, showing a link between tissue repair competence and
      nestin up-regulation under pathological conditions. In an in vitro assay system
      of human dental pulp explants, nestin is up-regulated after local application of
      bone morphogenic protein-4. A similar effect is seen in cultures of primary pulp
      cells during their differentiation into odontoblasts. Taken together, these
      results suggest that nestin plays a potential role in odontoblast differentiation
      during normal and pathological conditions and that bone morphogenic protein-4 is
      involved in nestin up-regulation.

PMID- 10880399
TI  - Regulation of liver inflammatory injury by signal transducer and activator of
      transcription-6.
AB  - Liver injury induced by hepatic ischemia/reperfusion is characterized by
      activation of the transcription factor NF-kappaB, increased production of tumor
      necrosis factor-alpha (TNFalpha), liver neutrophil accumulation, and
      hepatocellular damage. Exogenous administration of interleukin-4 (IL-4) or IL-13
      was recently shown to regulate this inflammatory injury in association with
      activation of signal transducer and activator of transcription-6 (STAT6). The
      objective of the present study was to determine whether STAT6 was required for
      the regulation of liver inflammation by IL-4 and IL-13. Wild-type and STAT6
      knockout mice underwent 90 minutes of hepatic ischemia followed by 8 hours of
      reperfusion. Hepatic ischemia/reperfusion in wild-type and STAT6 knockout mice
      significantly increased (P < 0.05) NF-kappaB activation, serum levels of
      TNFalpha, liver accumulation of neutrophils [measured by myeloperoxidase (MPO)
      content], and hepatocellular damage [measured by serum alanine aminotransferase
      (ALT)] compared to sham controls. In wild-type mice, activation of STAT6 was not
      observed after ischemia/reperfusion. Administration of 1 microg of IL-4 or IL-13
      at reperfusion reduced serum TNFalpha, liver neutrophil accumulation, and
      hepatocellular injury in wild-type mice. Treatment with IL-4 or IL-13 had no
      effect on liver NF-kappaB activation but significantly increased activation of
      STAT6. In STAT6 knockout mice, neither IL-4 nor IL-13 had any effect on TNFalpha,
      MPO, or ALT values, the regulatory effects of these cytokines being completely
      abolished. The data suggest that activation of STAT6 may regulate liver
      inflammatory injury.

PMID- 10880400
TI  - Gelatinase B (MMP-9) is not essential in the normal kidney and does not influence
      progression of renal disease in a mouse model of Alport syndrome.
AB  - Matrix metalloproteinases are matrix degrading enzymes implicated in many
      biological processes, including development and inflammation. Gelatinase B (gelB;
      also known as MMP-9) is expressed in the kidney and is hypothesized to be
      involved in basement membrane remodeling and in preventing pathogenic
      accumulation of extracellular matrix in the kidney. Inhibition of gelB activity
      in metanephric organ culture disrupts branching morphogenesis of the ureteric
      bud, suggesting that gelB plays a role in kidney development in vivo. We studied
      kidneys of gelB-deficient mice to search for developmental, histological,
      molecular, ultrastructural, and functional defects. Surprisingly, no differences
      between gelB-/- and control kidneys were detected, and renal function was normal
      in gelB mutants. In addition, gelB-/- embryonic kidneys developed normally in
      organ culture. Gelatinase B-deficient mice were bred with Col4a3-/- mice, a model
      for Alport syndrome, to determine whether gelB influences the progression of
      glomerulonephritis. This is an important question, as it has been hypothesized
      that proteases are involved in damaging Alport glomerular basement membrane.
      However, the presence or absence of gelB did not affect the rate of progression
      of renal disease. Thus, gelB does not have a discernible role in the normal
      kidney and gelB is not involved in the progression of glomerulonephritis in a
      mouse model of Alport syndrome.

PMID- 10880401
TI  - Intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and
      regulated on activation normal T cell expressed and secreted are expressed by
      human breast carcinoma cells and support eosinophil adhesion and activation.
AB  - Eosinophils are usually associated with parasitic and allergic diseases; however,
      eosinophilia is also observed in several types of human tumors, including breast
      carcinomas. In this study we examined several human breast carcinoma cell lines
      for adhesion molecule expression and the ability to bind and activate
      eosinophils. MDA-MB-435S and MDA-MB-468 cells constitutively expressed both
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) and this expression was enhanced by treatment with tumor necrosis factor
      alpha (TNF-alpha). BT-20 and SK-BR-3 cells only expressed ICAM-1 or VCAM-1 after
      stimulation with TNF-alpha. Eosinophils constitutively bound to MDA-MB-435S
      cells, but not to BT-20 cells. Stimulation with TNF-alpha slightly enhanced
      eosinophil adhesion to MDA-MB-435S cells and dramatically increased adhesion to
      BT-20 cells. Greater than 80% of eosinophil adhesion to these cell lines was
      blocked with an anti-alpha4-integrin monoclonal antibody. Both MDA-MB-435S and BT
      20 cells also released eosinophil activator(s). Supernatants from TNF-alpha
      treated, but not control-treated, cell lines increased eosinophil adhesion to
      fibronectin and increased eosinophil transmigration across fibronectin-coated
      transwell plates. Enzyme-linked immunosorbent assays showed that TNF-alpha
      stimulated breast carcinoma cells released the chemokine regulated on activation,
      T cell expressed and secreted (RANTES). Addition of an anti-RANTES antibody to
      breast carcinoma cell supernatants partially blocked eosinophil activation
      suggesting that RANTES in these supernatants was participating in eosinophil
      activation. These data show that TNF-alpha-stimulated breast carcinoma cells
      express mediators that can both bind and activate eosinophils, suggesting a
      mechanism for eosinophil localization to breast carcinoma sites.

PMID- 10880402
TI  - Loss of heterozygosity in fibrocystic change of the breast: genetic relationship
      between benign proliferative lesions and associated carcinomas.
AB  - Loss of heterozygosity (LOH), a genetic change frequently detected in cancer, can
      also occur in benign epithelial foci in the breast. To characterize LOH in benign
      breast tissue, 32 cases containing the various components of fibrocystic change
      in the absence of malignancy were studied. Microdissected foci of ductal
      hyperplasia, apocrine metaplasia, sclerosing adenosis, and morphologically normal
      terminal duct lobular units (TDLUs) were analyzed for LOH at 14 polymorphic loci
      representing seven chromosomal arms. LOH was detected in 22% of normal TDLUs
      (6/27), 17% of adenosis (4/23), 19% of hyperplasia (4/21), and 53% of apocrine
      metaplasia (10/19) specimens. Because of the high percentage of LOH in apocrine
      metaplasia in nonneoplastic specimens, the genetic relationship between apocrine
      metaplasia and cancer was studied in a panel of breast cancer cases. Of 14
      examples of apocrine metaplasia adjacent to a carcinoma, seven were found to have
      LOH with at least one marker. In all seven cases, the tumor and apocrine
      metaplasia shared LOH at one or more markers. The results demonstrate that LOH
      occurs frequently in the components of fibrocystic change as well as in normal
      TDLUs and suggest that foci of apocrine metaplasia can share a genetically
      altered precursor cell with an associated carcinoma.

PMID- 10880404
TI  - July 4, 2000

PMID- 10880405
TI  - Secondary prevention of coronary heart disease: the role of fibric acids.

PMID- 10880403
TI  - Age-related amyloid beta deposition in transgenic mice overexpressing both
      Alzheimer mutant presenilin 1 and amyloid beta precursor protein Swedish mutant
      is not associated with global neuronal loss.
AB  - To analyze the relationship between the deposition of amyloid beta peptides
      (Abeta) and neuronal loss in transgenic models of Alzheimer's disease (AD), we
      examined the frontal neocortex (Fc) and CA1 portion of hippocampus (CA1) in PSAPP
      mice doubly expressing AD-associated mutant presenilin 1 (PS1) and Swedish-type
      mutant beta amyloid precursor protein (APPsw) by morphometry of Abeta burden and
      neuronal counts. Deposition of Abeta was detected as early as 3 months of age in
      the Fc and CA1 of PSAPP mice and progressed to cover 28.3% of the superior
      frontal cortex and 18.4% of CA1 at 12 months: approximately 20- (Fc) and
      approximately 40- (CA1) fold greater deposition than in APPsw mice. There was no
      significant difference in neuronal counts in either CA1 or the frontal cortex
      between nontransgenic (non-tg), PS1 transgenic, APPsw, and PSAPP mice at 3 to 12
      months of age. In the PSAPP mice, there was disorganization of the neuronal
      architecture by compact amyloid plaques, and the average number of neurons was 8
      to 10% fewer than the other groups (NS, P > 0.10) in CA1 and 2 to 20% fewer in
      frontal cortex (NS, P = 0.31). There was no loss of total synaptophysin
      immunoreactivity in the Fc or dentate gyrus molecular layer of the 12-month-old
      PSAPP mice. Thus, although co-expression of mutant PS1 with Swedish mutant
      betaAPP leads to marked cortical and limbic Abeta deposition in an age-dependent
      manner, it does not result in the dramatic neuronal loss in hippocampus and
      association cortex characteristic of AD.

PMID- 10880406
TI  - Genetic differences in endothelial cells may determine atherosclerosis
      susceptibility.

PMID- 10880407
TI  - Mechanism of lumen enlargement during intracoronary stent implantation: an
      intravascular ultrasound study.
AB  - BACKGROUND: Intravascular ultrasound analysis has assessed mechanisms of lumen
      enlargement after nonstent interventions, but not after stenting. METHODS AND
      RESULTS: Preintervention and postintervention intravascular ultrasound was used
      to study 25 de novo native coronary lesions treated with single MultiLink stents
      without preatheroablation. External elastic membrane, lumen, and plaque and media
      (P&M) areas were measured every 1 mm to include the lesion and reference segments
      that were 5 mm proximal and distal to it. Lesion mean lumen area increased from
      4.0+/-1.0 mm(2) before the intervention to 8.8+/-2.0 mm(2) after the intervention
      (P<0.0001) as a result of an increase in mean external elastic membrane area (14.
      2+/-2.7 to 16.1+/-3.0 mm(2), P<0.0001) and a decrease in mean P&M area (10.2+/
      2.2 to 7.2+/-1.8 mm(2), P<0.0001). The decrease in lesion P&M was accompanied by
      an increase in both proximal reference mean P&M (7.0+/-1.9 to 8.4+/-2.0 mm(2),
      P<0.0001) and distal reference mean P&M (5.8+/-2.1 to 7.2+/-2.1 mm(2), P<0.0001).
      Volumetric analysis showed an axial redistribution of plaque away from the center
      of the lesion toward the reference segments to increase the plaque burden in both
      the proximal and distal reference segments. Total (lesion plus reference) mean
      P&M decreased from 8. 6+/-2.1 to 7.5+/-1.8 mm(2) (P<0.0001). CONCLUSIONS: The
      mechanisms of lumen enlargement after stenting involved (1) significant axial
      redistribution of plaque from the lesion into the reference segments, (2) vessel
      expansion, and (3) either plaque embolization or compression.

PMID- 10880408
TI  - Implications of stroke risk criteria on the anticoagulation decision in
      nonvalvular atrial fibrillation: the Anticoagulation and Risk Factors in Atrial
      Fibrillation (ATRIA) study.
AB  - BACKGROUND: Warfarin dramatically reduces the risk of stroke in patients with
      nonvalvular atrial fibrillation (NVAF) but increases the likelihood of bleeding.
      Accurately identifying patients who need anticoagulation is critical. We assessed
      the potential impact of prominent stroke risk classification schemes on this
      decision in a large sample of patients with NVAF. METHODS AND RESULTS: We used
      clinical and electrocardiographic databases to identify 13 559 ambulatory
      patients with NVAF from July 1996 through December 1997. We compared the
      proportion of patients classified as having a low enough stroke risk to receive
      aspirin using published criteria from the Atrial Fibrillation Investigators
      (AFI), American College of Chest Physicians (ACCP), and the Stroke Prevention in
      Atrial Fibrillation Investigators (SPAF). In this cohort, AFI criteria classified
      11% as having a low stroke risk, compared with 23% for ACCP and 29% for SPAF
      (kappa range, 0.44 to 0.85). This 2- to-3-fold increase in low stroke risk
      patients by ACCP and SPAF criteria primarily resulted from the inclusion of many
      older subjects (65 to 75 years+/-men >75 years) with no additional clinical
      stroke risk factors. CONCLUSIONS: The age threshold for assigning an increased
      stroke risk has a dramatic impact on whether to recommend warfarin in populations
      of patients with NVAF. Large, prospective studies with many stroke events are
      needed to precisely determine the relationship of age to stroke risk in AF and to
      identify which AF subgroups are at a sufficiently low stroke risk to forego
      anticoagulation.

PMID- 10880409
TI  - Serum soluble heat shock protein 60 is elevated in subjects with atherosclerosis
      in a general population.
AB  - BACKGROUND: Work from our laboratory has proven that increased titers of anti
      heat shock protein 60 (HSP60) antibodies are associated with atherosclerosis and
      that HSP60-reactive T-cells are present in atherosclerotic lesions. Recent
      studies from others demonstrated that HSP60 directly activates endothelial cells
      and macrophages. METHODS AND RESULTS: To explore the possibility that HSP60
      exists in the circulation, where it could exert its functions, we performed a
      population-based study with 826 subjects aged 40 to 79 years. The following items
      were measured in all participants: serum soluble HSP60 (sHSP60); anti-Escherichia
      coli lipopolysaccharide; anti-HSP65, anti-Chlamydia and anti-Helicobacter pylori
      antibodies; and a variety of acute phase reactants (C-reactive protein, alpha(1)
      antitrypsin, and ceruloplasmin) and markers of systemic inflammation. Carotid
      atherosclerosis was assessed twice (1990 and 1995), and 15 other risk factors
      were evaluated. Our data show that levels of sHSP60 were significantly elevated
      in subjects with prevalent/incident carotid atherosclerosis and that these levels
      were correlated with common carotid artery intima/media thickness. Multiple
      logistic regression analysis documented these associations as independent of age,
      sex, and other risk factors. Interestingly, sHSP60 was also correlated with anti
      lipopolysaccharide, anti-Chlamydia and anti-HSP60 antibodies, various markers of
      inflammation, and the presence of chronic infections. The risk of atherosclerosis
      associated with high sHSP60 levels was amplified when subjects had clinical
      and/or laboratory evidence of chronic infections. CONCLUSIONS: Our data provide
      the first evidence of a strong correlation between sHSP60 and atherosclerosis,
      suggesting that sHSP60 may play important roles in activating vascular cells and
      the immune system during the development of atherosclerosis.

PMID- 10880410
TI  - Secondary prevention by raising HDL cholesterol and reducing triglycerides in
      patients with coronary artery disease.
AB  - BACKGROUND: Coronary heart disease patients with low high-density lipoprotein
      cholesterol (HDL-C) levels, high triglyceride levels, or both are at an increased
      risk of cardiovascular events, but the clinical impact of raising HDL-C or
      decreasing triglycerides remains to be confirmed. METHODS AND RESULTS: In a
      double-blind trial, 3090 patients with a previous myocardial infarction or stable
      angina, total cholesterol of 180 to 250 mg/dL, HDL-C < or =45 mg/dL,
      triglycerides < or =300 mg/dL, and low-density lipoprotein cholesterol < or =180
      mg/dL were randomized to receive either 400 mg of bezafibrate per day or a
      placebo; they were followed for a mean of 6.2 years. The primary end point was
      fatal or nonfatal myocardial infarction or sudden death. Bezafibrate increased
      HDL-C by 18% and reduced triglycerides by 21%. The frequency of the primary end
      point was 13. 6% on bezafibrate versus 15.0% on placebo (P=0.26). After 6.2
      years, the reduction in the cumulative probability of the primary end point was
      7.3%, (P=0.24). In a post hoc analysis in the subgroup with high baseline
      triglycerides (> or =200 mg/dL), the reduction in the cumulative probability of
      the primary end point by bezafibrate was 39.5% (P=0.02). Total and noncardiac
      mortality rates were similar, and adverse events and cancer were equally
      distributed. CONCLUSIONS: Bezafibrate was safe and effective in elevating HDL-C
      levels and lowering triglycerides. An overall trend in a reduction of the
      incidence of primary end points was observed. The reduction in the primary end
      point in patients with high baseline triglycerides (> or =200 mg/dL) requires
      further confirmation.

PMID- 10880411
TI  - Pronounced benefit of coronary stenting and adjunctive platelet glycoprotein
      IIb/IIIa inhibition in complex atherosclerotic lesions.
AB  - BACKGROUND: Previous trials testing stents compared with balloon angioplasty
      excluded patients with complex lesions and did not assess the effect of
      adjunctive platelet IIb/IIIa inhibition. This analysis sought to assess the
      effect of stenting and abciximab specifically for patients with complex lesions.
      METHODS AND RESULTS: Patients with complex lesions (long, tandem, severely
      calcified, restenotic, thrombotic, or ostial; total occlusions; bifurcations;
      saphenous vein grafts; and multivessel interventions) from the Evaluation of PTCA
      to Improve Long-Term Outcome by c7E3 GP IIb/IIIa Receptor Blockade (EPILOG) and
      the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trials were
      included in the analysis. The 1-year combined death or myocardial infarction
      rates in the 4 treatment groups were as follows: balloon angioplasty/placebo,
      14.2%; stent/placebo, 15.8%; balloon angioplasty/abciximab, 7.6%; and
      stent/abciximab, 8.0% (P<0.001). Death rates were 3.2%, 3.1%, 2.1%, and 0.5%,
      respectively (P=0.03). The incidence of target vessel revascularization at 1 year
      was 30.5%, 18.0%, 24.4%, and 19.7% in the 4 groups, respectively (P<0.001). After
      adjustment for baseline differences, multivariate analysis demonstrated that the
      rate of death or myocardial infarction was independently reduced by balloon
      angioplasty/abciximab (hazard ratio, 0.51; P<0.001) and stent/abciximab (hazard
      ratio, 0.60; P=0.02) but was not affected by the use of stents alone. Conversely,
      target vessel revascularization was reduced by stent/placebo (hazard ratio, 0.53;
      P<0.001), stent/abciximab (hazard ratio, 0.58; P<0.001), and balloon
      angioplasty/abciximab (hazard ratio, 0.74; P=0.006) compared with balloon
      angioplasty/placebo, respectively. CONCLUSIONS: The combination of stenting and
      abciximab during percutaneous coronary interventions for patients with
      angiographically complex lesions confers additive long-term benefit with respect
      to death, myocardial infarction, and target vessel revascularization.

PMID- 10880412
TI  - Insertion-deletion polymorphism of the ACE gene modulates reversibility of
      endothelial dysfunction with ACE inhibition.
AB  - BACKGROUND: The aim of this study was to examine whether angiotensin-converting
      enzyme (ACE) inhibition improves coronary endothelial dysfunction in patients
      with atherosclerosis and its risk factors and whether this was related to the ACE
      insertion-deletion (I/D) polymorphism. METHODS AND RESULTS: In 56 patients with
      atherosclerosis or its risk factors, we studied endothelium-dependent responses
      with acetylcholine and endothelium-independent function with sodium
      nitroprusside, before and after ACE inhibition with enalaprilat. Enalaprilat did
      not alter either resting coronary tone or vasodilation with sodium nitroprusside.
      However, it potentiated the coronary microvascular and epicardial responses with
      acetylcholine; coronary blood flow increased from 82+/-7 to 90+/-8 mL/min
      (P=0.05) after enalaprilat. Patients with depressed endothelial function
      (P<0.001) and those with ACE DD or ID genotypes (P=0.002) but not those
      homozygous for the I allele had the greatest improvement by multivariate
      analysis. Similarly, acetylcholine-mediated epicardial vasomotion improved in
      segments that initially constricted (endothelial dysfunction): from -10.1+/-1% to
      -1.4+/-2% (P<0.001) after enalaprilat. No augmentation was observed in segments
      that dilated (normal endothelial dysfunction) with acetylcholine. Patients with
      the D allele, hypercholesterolemia, and smokers (all P<0.05) had greater
      improvement. CONCLUSIONS: Acute ACE inhibition improves coronary epicardial and
      microvascular endothelium-dependent vasomotion in patients with atherosclerosis
      or its risk factors who have endothelial dysfunction and presence of the D
      allele.

PMID- 10880413
TI  - Chronic subclinical inflammation as part of the insulin resistance syndrome: the
      Insulin Resistance Atherosclerosis Study (IRAS).
AB  - BACKGROUND: Inflammation has been suggested as a risk factor for the development
      of atherosclerosis. Recently, some components of the insulin resistance syndrome
      (IRS) have been related to inflammatory markers. We hypothesized that insulin
      insensitivity, as directly measured, may be associated with inflammation in
      nondiabetic subjects. METHODS AND RESULTS: We studied the relation of C-reactive
      protein (CRP), fibrinogen, and white cell count to components of IRS in the
      nondiabetic population of the Insulin Resistance Atherosclerosis Study (IRAS)
      (n=1008; age, 40 to 69 years; 33% with impaired glucose tolerance), a
      multicenter, population-based study. None of the subjects had clinical coronary
      artery disease. Insulin sensitivity (S(I)) was measured by a frequently sampled
      intravenous glucose tolerance test, and CRP was measured by a highly sensitive
      competitive immunoassay. All 3 inflammatory markers were correlated with several
      components of the IRS. Strong associations were found between CRP and measures of
      body fat (body mass index, waist circumference), S(I), and fasting insulin and
      proinsulin (all correlation coefficients >0.3, P<0.0001). The associations were
      consistent among the 3 ethnic groups of the IRAS. There was a linear increase in
      CRP levels with an increase in the number of metabolic disorders. Body mass
      index, systolic blood pressure, and S(I) were related to CRP levels in a
      multivariate linear regression model. CONCLUSIONS: We suggest that chronic
      subclinical inflammation is part of IRS. CRP, a predictor of cardiovascular
      events in previous reports, was independently related to S(I). These findings
      suggest potential benefits of anti-inflammatory or insulin-sensitizing treatment
      strategies in healthy individuals with features of IRS.

PMID- 10880414
TI  - Coronary artery flow velocity is related to lumen area and regional left
      ventricular mass.
AB  - BACKGROUND: Coronary flow velocity varies widely between individuals, even at
      rest. Because of this variation, indices with less apparent deviation, such as
      the ratio of hyperemic to resting velocity (coronary flow reserve), have been
      more commonly studied. We tested the hypothesis that the flow continuity
      principle could be used to model resting coronary flow, and we examined the
      resulting velocity relationship. METHODS AND RESULTS: We studied coronary
      velocity in 59 patients using a Doppler wire to measure resting and hyperemic
      average peak velocities in the left anterior descending artery. Quantitative
      techniques were used to calculate lumen cross-sectional area and the lengths of
      all distal coronary branches. Branch lengths were used to estimate regional left
      ventricular mass. We then calculated the ratio of lumen area to regional mass
      (A/m). Regional perfusion was estimated from the double product of heart rate and
      systolic blood pressure. Resting velocity (V) varied inversely with A/m ratio
      [V=46.5/(A/m); r=0.68, P<0.001]. Disease in the left anterior descending artery
      was categorized as none or luminal irregularities only (n=22), mild (n=15), or
      moderate (n=22). The A/m ratio declined across these groups (8.7+/-4.0, 8.5+/
      6.2, and 5. 6+/-3.0 mm(2)/100 g, respectively; P<0.04), and the resting average
      peak velocity increased (27+/-16, 33+/-11, and 37+/-20 cm/s, respectively;
      P=0.06). CONCLUSIONS: Resting coronary artery flow velocity is inversely related
      to the ratio of lumen area to regional left ventricular mass. Higher resting
      velocities are found when insufficient lumen size exists for the distal
      myocardial bed, as occurs with diffuse mild or moderate coronary atherosclerosis.

PMID- 10880415
TI  - Assessment of myocardial perfusion by harmonic power Doppler imaging at rest and
      during adenosine stress: comparison with (99m)Tc-sestamibi SPECT imaging.
AB  - BACKGROUND: Harmonic power Doppler imaging (HPDI) is a novel technique for
      assessing myocardial perfusion by contrast echocardiography in humans. The
      purpose of this study was to compare myocardial perfusion by HPDI with that
      obtained by (99m)Tc-sestamibi single photon emission computed tomography (SPECT)
      during rest and pharmacological stress. METHODS AND RESULTS: HPDI was performed
      on 123 patients who were referred for SPECT imaging for known or suspected
      coronary artery disease. Images were obtained at baseline and during adenosine
      infusion (0.14 mg. kg(-)(1). min(-)(1)x6 minutes) in 3 apical views. Myocardial
      perfusion by HPDI was graded for each coronary territory as absent, patchy, or
      full. The persistence of absent or patchy myocardial perfusion by HPDI between
      rest and adenosine was interpreted as a fixed defect, whereas any decrease in
      perfusion grade was interpreted as a reversible defect. Overall concordance
      between HPDI and SPECT was 83 (81%) of 103 for normal versus abnormal perfusion.
      Agreement between the 2 methods for each of the 3 coronary territories was 81%
      (kappa=0.57) for the left anterior descending artery, 76% (kappa=0.52) for the
      right coronary artery, and 72% (kappa=0.40) for the left circumflex artery.
      Discrepancies between the 2 techniques were most notable in the circumflex
      territory, where fixed defects were observed in 33% by HPDI but in only 14% by
      SPECT (chi(2)=15.8, P=0.0001). CONCLUSIONS: This study demonstrates that HPDI can
      reliably detect myocardial perfusion during pharmacological stress, although
      there was a significantly higher number of falsely abnormal results in the
      circumflex territory.

PMID- 10880416
TI  - Effects of continuous positive airway pressure on cardiovascular outcomes in
      heart failure patients with and without Cheyne-Stokes respiration.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) improves cardiac function
      in patients with congestive heart failure (CHF) who also have Cheyne-Stokes
      respiration and central sleep apnea (CSR-CSA). However, the effects of CPAP in
      CHF patients without CSR-CSA have not been tested, and the long-term effects of
      this treatment on clinical cardiovascular outcomes are unknown. METHODS AND
      RESULTS: We conducted a randomized, controlled trial in which 66 patients with
      CHF (29 with and 37 without CSR-CSA) were randomized to either a group that
      received CPAP nightly or to a control group. Change in left ventricular ejection
      fraction (LVEF) from baseline to 3 months and the combined mortality-cardiac
      transplantation rate over the median 2.2-year follow-up period were compared
      between the CPAP-treated and control groups. For the entire group of patients,
      CPAP had no significant effect on LVEF, but it was associated with a 60% relative
      risk reduction (95% confidence interval, 2% to 64%) in mortality-cardiac
      transplantation rate in patients who complied with CPAP therapy. Stratified
      analysis of patients with and without CSR-CSA revealed that those with CSR-CSA
      experienced both a significant improvement in LVEF at 3 months and a relative
      risk reduction of 81% (95% confidence interval, 26% to 95%) in the mortality
      cardiac transplantation rate of those who used CPAP. CPAP had no significant
      effect on either of these outcomes in patients without CSR-CSA. CONCLUSIONS: CPAP
      improves cardiac function in CHF patients with CSR-CSA but not in those without
      it. Although not definitive, our findings also suggest that CPAP can reduce the
      combined mortality-cardiac transplantation rate in those CHF patients with CSR
      CSA who comply with therapy.

PMID- 10880417
TI  - Initiation of atrial fibrillation by ectopic beats originating from the superior
      vena cava: electrophysiological characteristics and results of radiofrequency
      ablation.
AB  - BACKGROUND: The superior vena cava (SVC) has cardiac musculature extending from
      the right atrium. However, no previous study in humans has given details
      regarding the ectopic foci that initiate paroxysmal atrial fibrillation (PAF),
      which may originate from the SVC. METHODS AND RESULTS: A total of 130 patients
      with frequent attacks of PAF initiated by ectopic beats were included. Eight
      patients (6%) had spontaneous AF initiated by a burst of rapid ectopic beats from
      the SVC (located 19+/-7 mm above the junction of the SVC and right atrium), which
      was confirmed by multiplane angiographic and intracardiac echocardiographic
      visualization and was marked by a sharp SVC potential preceding atrial activity.
      During initial repetitive discharges, the group with SVC ectopy had a higher
      incidence of intravenous conduction block than the group with pulmonary vein
      ectopy (75% versus 37%; P=0.03). The activation time of the earliest intracardiac
      ectopic activities relative to ectopic P wave onset was significantly shorter in
      the SVC ectopy than the pulmonary vein ectopy group (37+/-15 versus 84+/-32 ms;
      P<0. 001). After 5+/-3 applications of radiofrequency energy, AF was eliminated.
      SVC angiography after ablation revealed a local indentation of the venous wall in
      one patient. Two patients manifested coexisting sinus rhythm and a "focal"
      fibrillating activity confined inside the SVC after radiofrequency ablation.
      During a follow-up period of 9+/-3 months, all 8 patients were free of
      antiarrhythmic drugs, without tachycardia recurrence or symptoms of SVC
      obstruction. CONCLUSIONS: Ectopic beats initiating PAF can originate from the
      SVC. A radiofrequency current delivered to eliminate these ectopies is a highly
      effective and safe way to prevent PAF.

PMID- 10880418
TI  - Endothelial responses to oxidized lipoproteins determine genetic susceptibility
      to atherosclerosis in mice.
AB  - BACKGROUND: Oxidized LDL has been found within the subendothelial space, and it
      exhibits numerous atherogenic properties, including induction of inflammatory
      genes. We examined the possibility that variations in endothelial response to
      minimally modified LDL (MM-LDL) constitute one of the genetic components in
      atherosclerosis. METHODS AND RESULTS: By a novel explant technique, endothelial
      cells (ECs) were isolated from the aorta of inbred mouse strains with different
      susceptibilities to diet-induced atherosclerosis. Responses to MM-LDL were
      evaluated by examining the expression of inflammatory genes involved in
      atherosclerosis, including monocyte chemotactic protein-1 (MCP-1) and macrophage
      colony-stimulating factor (M-CSF), an oxidative stress gene, heme oxygenase-1 (HO
      1), and other, noninflammatory, genes. ECs from the susceptible mouse strain
      C57BL/6J exhibited dramatic induction of MCP-1, M-CSF, and HO-1, whereas ECs from
      the resistant strain C3H/HeJ showed little or no induction. In contrast, ECs from
      the 2 strains responded similarly to lipopolysaccharide. CONCLUSIONS: These data
      provide strong evidence that genetic factors in atherosclerosis act at the level
      of the vessel wall.

PMID- 10880419
TI  - Vitamin E reduces the uptake of oxidized LDL by inhibiting CD36 scavenger
      receptor expression in cultured aortic smooth muscle cells.
AB  - BACKGROUND: Vitamin E is well known as an antioxidant, and numerous studies
      suggest that it has a preventive role in atherosclerosis, although the mechanism
      of action still remains unclear. METHODS AND RESULTS: The original aim of this
      study was to establish whether alpha-tocopherol (the most active form of vitamin
      E) acts at the earliest events on the cascade of atherosclerosis progression,
      that of oxidized LDL (oxLDL) uptake and foam-cell formation. We show here that
      the CD36 scavenger receptor (a specific receptor for oxLDL) is expressed in
      cultured human aortic smooth muscle cells (SMCs). Treatment of SMCs and HL-60
      macrophages with alpha-tocopherol (50 micromol/L, a physiological concentration)
      downregulates CD36 expression by reducing its promoter activity. Furthermore, we
      find that alpha-tocopherol treatment of SMCs leads to a reduction of oxLDL
      uptake. CONCLUSIONS: This study indicates that CD36 is expressed in cultured
      human SMCs. In these cells, CD36 transports oxLDL into the cytosol. alpha
      Tocopherol inhibits oxLDL uptake by a mechanism involving downregulation of CD36
      mRNA and protein expression. Therefore, the beneficial effect of alpha-tocopherol
      against atherosclerosis can be explained, at least in part, by its effect of
      lowering the uptake of oxidized lipoproteins, with consequent reduction of foam
      cell formation.

PMID- 10880420
TI  - Brief antecedent ischemia enhances recombinant tissue plasminogen activator
      induced coronary thrombolysis by adenosine-mediated mechanism.
AB  - BACKGROUND: Clinical studies have implicated preinfarct angina (brief antecedent
      ischemia/reperfusion [I/R]) as a predictor of more rapid thrombolysis and lower
      rates of reocclusion. However, the effects of antecedent ischemia on the efficacy
      of thrombolysis have not been rigorously assessed. Using a canine model of
      coronary thrombosis, we aimed to (1) reproduce these clinical findings and (2)
      determine whether release of adenosine (a potent inhibitor of platelet
      aggregation via stimulation of platelet A(2) receptors) during brief I/R
      contributes to this improved patency. METHODS AND RESULTS: To address our first
      objective, we compared the time required to achieve lysis with recombinant tissue
      plasminogen activator and patency during the first 2 hours after lysis in dogs in
      which 1-hour thrombotic occlusion was preceded by brief I/R (10-minute coronary
      occlusion/10-minute reperfusion) versus 20-minute uninterrupted perfusion
      (controls). Time to lysis was accelerated in the I/R group versus the control
      group (11+/-1 versus 35+/-6 minutes, P=0.004). In addition, the duration of
      subsequent reocclusion was reduced (17+/-12 versus 30+/-11 minutes), and the area
      of the flow-time profile (normalized to baseline flow x 120 minutes) was
      increased (64+/-12% versus 35+/-7%, P=0.04) in the I/R cohort. The protocol was
      then repeated, but all dogs were pretreated with the adenosine A(2)/A(1)
      antagonist CGS 15943 (CGS, 1.5 mg/kg). Time to lysis (38 versus 39 minutes) and
      subsequent patency were comparable in the CGS+control group versus the CGS+I/R
      group. CONCLUSIONS: Brief antecedent I/R enhances the efficacy of coronary
      thrombolysis in this canine model, which is due, at least in part, to an
      adenosine-mediated mechanism.

PMID- 10880421
TI  - Alterations by norepinephrine of cardiac sympathetic nerve terminal function and
      myocardial beta-adrenergic receptor sensitivity in the ferret: normalization by
      antioxidant vitamins.
AB  - BACKGROUND: Chronic excessive norepinephrine (NE) causes cardiac sympathetic
      nerve terminal abnormalities, myocardial beta-adrenergic receptor downregulation,
      and beta-adrenergic subsensitivity. The present study was carried out to
      determine whether these changes could be prevented by antioxidants. METHODS AND
      RESULTS: Ferrets were administered either NE (1.33 mg/d) or vehicle by use of
      subcutaneous pellets for 4 weeks. Animals were simultaneously assigned to receive
      either antioxidant vitamins (beta-carotene, ascorbic acid, and alpha-tocopherol)
      or placebo pellets. NE increased plasma NE 4- to 5-fold but had no effect on
      heart rate, heart weight, arterial pressure, or left ventricular systolic
      function. However, myocardial NE uptake activity and NE uptake-1 site density
      were reduced, as well as cardiac neuronal NE, tyrosine hydroxylase, and
      neuropeptide Y. In addition, there was a decrease in myocardial beta-adrenergic
      receptor density with a selective decrease of the beta(1)-receptor subtype,
      reduction of the high-affinity site for isoproterenol, decreased basal adenylyl
      cyclase activity, and the adenylyl cyclase responses to isoproterenol, Gpp(NH)p,
      and forskolin. All of these changes were prevented by antioxidant vitamins. The
      effects of NE on myocardial beta-adrenergic receptor density, NE uptake-1 carrier
      site density, and neuronal NE were also prevented by superoxide dismutase or
      Trolox C. CONCLUSIONS: The toxic effects of NE on the sympathetic nerve terminals
      are mediated via the formation of NE-derived oxygen free radicals. Preservation
      of the neuronal NE reuptake mechanism is functionally important, because the
      antioxidants also prevented myocardial beta-adrenergic receptor downregulation
      and postreceptor abnormalities. Thus, antioxidant therapy may be beneficial in
      heart failure, in which cardiac NE release is increased.

PMID- 10880422
TI  - Contrasting efficacy of dofetilide in differing experimental models of atrial
      fibrillation.
AB  - BACKGROUND: Rapid atrial pacing (RAP) and congestive heart failure (CHF) produce
      different experimental substrates for atrial fibrillation (AF). We tested the
      hypothesis that AF maintained by different substrates responds differently to
      antiarrhythmic-drug therapy. METHODS AND RESULTS: The class III antiarrhythmic
      agent dofetilide was given intravenously at doses of 10 (D10) and 80 (D80)
      microg/kg to dogs with AF induced either (1) after 7 days of RAP at 400 bpm or
      (2) in the presence of CHF induced by rapid ventricular pacing. Dofetilide
      terminated AF in all CHF dogs, but D10 failed to terminate AF in any RAP dog, and
      D80 terminated AF in only 1 of 5 RAP dogs (20%) (P<0.01 for efficacy in CHF
      versus RAP dogs). Dofetilide was highly effective in preventing AF induction by
      atrial burst pacing in dogs with CHF but was totally ineffective in dogs with
      RAP. Dofetilide increased atrial effective refractory period and AF cycle length
      to a greater extent in CHF dogs. Epicardial mapping with 248 bipolar electrodes
      showed that CHF-related AF was often due to macroreentry, with dofetilide
      terminating AF by causing block in reentry circuits. RAP-related AF was due to
      multiple-wave front reentry, with dofetilide slowing reentry and decreasing the
      number of simultaneous waves, but not sufficiently to stop AF. CONCLUSIONS: The
      mechanism underlying AF importantly influences dofetilide efficacy. The
      dependence of drug efficacy in AF on the underlying mechanism has potentially
      significant implications for antiarrhythmic drug use and development and may
      explain the well-known therapeutic resistance of longer-duration AF.

PMID- 10880423
TI  - Endogenous tissue factor pathway inhibitor modulates thrombus formation in an in
      vivo model of rabbit carotid artery stenosis and endothelial injury.
AB  - BACKGROUND: Tissue factor pathway inhibitor (TFPI) is the sole known inhibitor of
      the extrinsic coagulation pathway of physiological importance; however, its role
      in modulating thrombosis in vivo is still unclear. METHODS AND RESULTS:
      Intravascular thrombosis was initiated by placing an external constrictor around
      endothelially injured rabbit carotid arteries (n=10). Carotid blood flow velocity
      was measured by a Doppler flow probe. After placement of the constrictor, cyclic
      flow reductions (CFRs), due to recurrent thrombosis, developed at the site of
      stenosis. Transstenotic TFPI plasma activity was measured in blood samples before
      induction of CFRs and after 30, 60, and 180 minutes of CFRs. TFPI plasma activity
      distal to the site of thrombosis was significantly lower than the corresponding
      proximal values at 30, 60, and 180 minutes of CFRs. In addition, a progressive
      decrease in TFPI plasma activity was observed in both the proximal and the distal
      samples, indicating consumption of TFPI during thrombus formation. In 10
      additional rabbits, CFRs were abolished by administration of aspirin (10 mg/kg).
      In the animals in which aspirin abolished CFRs, endogenous TFPI was depleted by a
      bolus of a polyclonal antibody against rabbit TFPI, and the effects on
      restoration of CFRs were monitored. In 5 of 6 animals in which aspirin abolished
      CFRs, depletion of endogenous TFPI activity caused full restoration of CFRs.
      CONCLUSIONS: The data of the present study support the involvement of endogenous
      TFPI in the process of thrombus formation in vivo and its active role in
      modulating arterial thrombosis.

PMID- 10880424
TI  - A classification of unstable angina revisited.
AB  - Unstable angina is a critical phase of coronary heart disease with widely
      variable symptoms and prognosis. A decade ago, a classification of unstable
      angina based on clinical symptoms was introduced. This system was then validated
      by prospective clinical studies to correlate with the prognosis and was linked to
      angiographic and histological findings. It has been used to categorize patients
      in many large clinical trials. In recent years, the pathophysiological roles of
      platelet activation and inflammation in unstable angina have been elucidated.
      Subsequently, improved markers of myocardial injury, acute-phase proteins, and
      hemostatic markers that may be associated with clinical outcomes have been
      identified. Particularly, cardiac-specific troponin T and troponin I have been
      shown to represent the best predictors of early risk in patients with angina at
      rest. Accordingly, it is suggested that the original classification be extended
      by subclassifying one large group of unstable angina patients, ie, those with
      angina at rest within the past 48 hours (class IIIB), into troponin-positive
      (T(pos)) and troponin-negative (T(neg)) patients. The 30-days risk for death and
      myocardial infarction is considered to be up to 20% in class IIIB-T(pos) but <2%
      in class IIIB-T(neg) patients. Initial results suggest that troponins may
      function as surrogate markers for thrombus formation and can effectively guide
      therapy with glycoprotein IIb/IIIa antagonists or low-molecular-weight heparins.
      These observations provide additional impetus for adding the measurement of these
      markers to the clinical classification and represent a novel concept of treating
      these high-risk patients.

PMID- 10880425
TI  - Images in cardiovascular medicine. Ventricular tachycardia: a complication of an
      intramyocardial echinococcal cyst.

PMID- 10880426
TI  - American College of Cardiology/American Heart Association Expert Consensus
      document on electron-beam computed tomography for the diagnosis and prognosis of
      coronary artery disease.

PMID- 10880427
TI  - Meeting highlights: highlights of the 72nd Scientific Sessions of the American
      Heart Association.

PMID- 10880428
TI  - Coronary artery fly-through using electron beam computed tomography.
AB  - BACKGROUND: Virtual reality techniques have recently been introduced into
      clinical medicine. This study examines the possibility of coronary artery fly
      through using a dataset obtained by noninvasive coronary angiography with
      contrast-enhanced electron-beam computed tomography. METHODS AND RESULTS: Ten
      patients were examined, and 40 to 60 transaxial tomograms (thickness, 1.5 mm; in
      plane pixel dimensions, approximately 0.5x0.5 mm) were obtained after intravenous
      contrast injection. The datasets were processed on a graphics workstation using
      volume-rendering software. For fly-throughs, the contrast-enhanced lumen was made
      transparent and other tissue was made opaque. Then, key frames were selected in a
      path through the vessel, with software interpolation of frames between key
      frames. A typical movie contained 150 to 300 frames (10 to 15 key frames). Fly
      throughs of coronary bypass grafts (n=3), left anterior descending arteries (LAD;
      n=6), and the intermediate branch (n=1) were reconstructed. Coronary
      calcifications were seen in 3 patients. The fly-through of the intermediate
      branch, the bypass grafts, and one of the LADs did not show any irregularities.
      In 2 cases, a stenosis was visible in the LAD; its presence was confirmed by
      conventional coronary angiography. CONCLUSIONS: Recent developments in fast
      volume rendering using special-purpose hardware in combination with noninvasive
      coronary angiography with electron beam computed tomography have provided the
      possibility of performing coronary artery fly-throughs.

PMID- 10880429
TI  - Pheochromocytoma-induced cardiomyopathy.

PMID- 10880431
TI  - Crystal structure of cystalysin from Treponema denticola: a pyridoxal 5'
      phosphate-dependent protein acting as a haemolytic enzyme.
AB  - Cystalysin is a C(beta)-S(gamma) lyase from the oral pathogen Treponema denticola
      catabolyzing L-cysteine to produce pyruvate, ammonia and H(2)S. With its ability
      to induce cell lysis, cystalysin represents a new class of pyridoxal 5'-phosphate
      (PLP)-dependent virulence factors. The crystal structure of cystalysin was solved
      at 1.9 A resolution and revealed a folding and quaternary arrangement similar to
      aminotransferases. Based on the active site architecture, a detailed catalytic
      mechanism is proposed for the catabolism of S-containing amino acid substrates
      yielding H(2)S and cysteine persulfide. Since no homologies were observed with
      known haemolysins the cytotoxicity of cystalysin is attributed to this chemical
      reaction. Analysis of the cystalysin-L-aminoethoxyvinylglycine (AVG) complex
      revealed a 'dead end' ketimine PLP derivative, resulting in a total loss of
      enzyme activity. Cystalysin represents an essential factor of adult
      periodontitis, therefore the structure of the cystalysin-AVG complex may provide
      the chemical basis for rational drug design.

PMID- 10880430
TI  - The ErbB signaling network: receptor heterodimerization in development and
      cancer.

PMID- 10880432
TI  - The bacterial cell-division protein ZipA and its interaction with an FtsZ
      fragment revealed by X-ray crystallography.
AB  - In Escherichia coli, FtsZ, a homologue of eukaryotic tubulins, and ZipA, a
      membrane-anchored protein that binds to FtsZ, are two essential components of the
      septal ring structure that mediates cell division. Recent data indicate that ZipA
      is involved in the assembly of the ring by linking FtsZ to the cytoplasmic
      membrane and that the ZipA-FtsZ interaction is mediated by their C-terminal
      domains. We present the X-ray crystal structures of the C-terminal FtsZ-binding
      domain of ZipA and a complex between this domain and a C-terminal fragment of
      FtsZ. The ZipA domain is a six-stranded beta-sheet packed against three alpha
      helices and contains the split beta-alpha-beta motif found in many RNA-binding
      proteins. The uncovered side of the sheet incorporates a shallow hydrophobic
      cavity exposed to solvent. In the complex, the 17-residue FtsZ fragment occupies
      this entire cavity of ZipA and binds as an extended beta-strand followed by alpha
      helix. An alanine-scanning mutagenesis analysis of the FtsZ fragment was also
      performed, which shows that only a small cluster of the buried FtsZ side chains
      is critical in binding to ZipA.

PMID- 10880433
TI  - Structure of the active core of human stem cell factor and analysis of binding to
      its receptor kit.
AB  - Stem cell factor (SCF) is an early-acting hematopoietic cytokine that elicits
      multiple biological effects. SCF is dimeric and occurs in soluble and membrane
      bound forms. It transduces signals by ligand- mediated dimerization of its
      receptor, Kit, which is a receptor tyrosine kinase related to the receptors for
      platelet-derived growth factor (PDGF), macrophage colony-stimulating factor, Flt
      3 ligand and vascular endothelial growth factor (VEGF). All of these have
      extracellular ligand-binding portions composed of immunoglobulin-like repeats. We
      have determined the crystal structure of selenomethionyl soluble human SCF at 2.2
      A resolution by multiwavelength anomalous diffraction phasing. SCF has the
      characteristic helical cytokine topology, but the structure is unique apart from
      core portions. The SCF dimer has a symmetric 'head-to-head' association. Using
      various prior observations, we have located potential Kit-binding sites on the
      SCF dimer. A superimposition of this dimer onto VEGF in its complex with the
      receptor Flt-1 places the binding sites on SCF in positions of topographical and
      electrostatic complementarity with the Kit counterparts of Flt-1, and a similar
      model can be made for the complex of PDGF with its receptor.

PMID- 10880434
TI  - Cultivar-specific avirulence and virulence functions assigned to avrPphF in
      Pseudomonas syringae pv. phaseolicola, the cause of bean halo-blight disease.
AB  - The avrPphF gene was cloned from Pseudomonas syringae pathovar phaseolicola
      (PPH:) races 5 and 7, based on its ability to confer avirulence towards bean
      cultivars carrying the R1 gene for halo-blight resistance, such as Red Mexican.
      avrPphF comprised two open reading frames, which were both required for function,
      and was located on a 154 kb plasmid (pAV511) in PPH: Strain RW60 of PPH:, lacking
      pAV511, displayed a loss in virulence to a range of previously susceptible
      cultivars such as Tendergreen and Canadian Wonder. In Tendergreen virulence was
      restored to RW60 by avrPphF alone, whereas subcloned avrPphF in the absence of
      pAV511 greatly accelerated the hypersensitive resistance reaction caused by RW60
      in Canadian Wonder. A second gene from pAV511, avrPphC, which controls avirulence
      to soybean, was found to block the activity of avrPphF in Canadian Wonder, but
      not in Red Mexican. avrPphF also conferred virulence in soybean. The multiple
      functions of avrPphF illustrate how effector proteins from plant pathogens have
      evolved to be recognized by R gene products and, therefore, be classified as
      encoded by avirulence genes.

PMID- 10880435
TI  - The yeast prion [URE3] can be greatly induced by a functional mutated URE2
      allele.
AB  - The non-Mendelian element [URE3] of yeast is considered to be a prion form of the
      Ure2 protein. The [URE3] phenotype occurs at a frequency of 10(-5) in haploid
      yeast strains, is reversible, and its frequency is increased by overexpressing
      the URE2 gene. We created a new mutant of the Ure2 protein, called H2p, which
      results in a 1000-fold increase in the rate of [URE3] occurrence. To date, only
      the overexpression of various C-terminal truncated mutants of Ure2p gives rise to
      a comparable level. The h2 allele is, thus, the first characterized URE2 allele
      that induces prion formation when expressed at a low level. By shuffling mutated
      and wild-type domains of URE2, we also created the first mutant Ure2 protein that
      is functional and induces prion formation. We demonstrate that the domains of
      URE2 function synergistically in cis to induce [URE3] formation, which highlights
      the importance of intramolecular interactions in Ure2p folding. Additionally, we
      show using a green fluorescent protein (GFP) fusion protein that the h2 allele
      exhibits numerous filiform structures that are not generated by the wild-type
      protein.

PMID- 10880436
TI  - Identification and cell cycle control of a novel pilus system in Caulobacter
      crescentus.
AB  - Pilus assembly in CAULOBACTER: crescentus occurs during a short period of the
      cell cycle and pili are only present at the flagellar pole of the swarmer cell.
      Here we report a novel assay to visualize pili by light microscopy that led to
      the purification of CAULOBACTER: pili and the isolation of a cluster of seven
      genes, including the major pilin subunit gene pilA. This gene cluster encodes a
      novel group of pilus assembly proteins. We have shown that the pilA promoter is
      activated late in the cell cycle and that transcription of the pilin subunit
      plays an important role in the timing of pilus assembly. pilA transcription is
      regulated by the global two-component response regulator CtrA, which is essential
      for the expression of multiple cell cycle events, providing a direct link between
      assembly of the pilus organelle and bacterial cell cycle control.

PMID- 10880438
TI  - alpha-latrotoxin triggers transmitter release via direct insertion into the
      presynaptic plasma membrane.
AB  - alpha-latrotoxin, a component of black widow spider venom, binds to presynaptic
      nerve terminals and stimulates massive neurotransmitter release. Previous studies
      have demonstrated that alpha-latrotoxin first binds to two high-affinity
      receptors on nerve terminals, neurexins and CLs (CIRLs and latrophilins), and
      then executes a critical, second step of unknown nature that stimulates
      neurotransmitter release. We now demonstrate that incubation of alpha-latrotoxin
      with synaptosomes at 0 degrees C results in its peripheral membrane association.
      Incubation at 37 degrees C, however, converts the toxin into an operationally
      integral membrane protein, and induces generation of a protease-resistant
      fragment that consists of the entire N-terminal domain of alpha-latrotoxin and
      becomes protease sensitive after lysis of synaptosomes. Our data suggest that
      alpha-latrotoxin inserts into the presynaptic plasma membrane after receptor
      binding, resulting in an intracellular location of the N-terminal sequences.
      Membrane insertion of the N-terminal domain of alpha-latrotoxin occurs
      spontaneously, independently of membrane recycling or transmembrane ion
      gradients. We postulate that alpha-latrotoxin acts intracellularly in triggering
      release, and propose that non-selective cation channels induced by alpha
      latrotoxin may be a by-product of membrane insertion.

PMID- 10880437
TI  - Salmonella maintains the integrity of its intracellular vacuole through the
      action of SifA.
AB  - A method based on the Competitive Index was used to identify Salmonella
      typhimurium virulence gene interactions during systemic infections of mice.
      Analysis of mixed infections involving single and double mutant strains showed
      that OmpR, the type III secretion system of Salmonella pathogenicity island 2
      (SPI-2) and SifA [required for the formation in epithelial cells of lysosomal
      glycoprotein (lgp)-containing structures, termed Sifs] are all involved in the
      same virulence function. sifA gene expression was induced after Salmonella entry
      into host cells and was dependent on the SPI-2 regulator ssrA. A sifA(-) mutant
      strain had a replication defect in macrophages, similar to that of SPI-2 and
      ompR(-) mutant strains. Whereas wild-type and SPI-2 mutant strains reside in
      vacuoles that progressively acquire lgps and the vacuolar ATPase, the majority of
      sifA(-) bacteria lost their vacuolar membrane and were released into the host
      cell cytosol. We propose that the wild-type strain, through the action of SPI-2
      effectors (including SpiC), diverts the Salmonella-containing vacuole from the
      endocytic pathway, and subsequent recruitment and maintenance of vacuolar
      ATPase/lgp-containing membranes that enclose replicating bacteria is mediated by
      translocation of SifA.

PMID- 10880439
TI  - Inhibition of human ether a go-go potassium channels by Ca(2+)/calmodulin.
AB  - Intracellular Ca(2+) inhibits voltage-gated potassium channels of the ether a go
      go (EAG) family. To identify the underlying molecular mechanism, we expressed the
      human version hEAG1 in Xenopus oocytes. The channels lost Ca(2+) sensitivity when
      measured in cell-free membrane patches. However, Ca(2+) sensitivity could be
      restored by application of recombinant calmodulin (CaM). In the presence of CaM,
      half inhibition of hEAG1 channels was obtained in 100 nM Ca(2+). Overlay assays
      using labelled CaM and glutathione S-transferase (GST) fusion fragments of hEAG1
      demonstrated direct binding of CaM to a C-terminal domain (hEAG1 amino acids 673
      770). Point mutations within this section revealed a novel CaM-binding domain
      putatively forming an amphipathic helix with both sides being important for
      binding. The binding of CaM to hEAG1 is, in contrast to Ca(2+)-activated
      potassium channels, Ca(2+) dependent, with an apparent K(D) of 480 nM. Co
      expression experiments of wild-type and mutant channels revealed that the binding
      of one CaM molecule per channel complex is sufficient for channel inhibition.

PMID- 10880440
TI  - Thrombospondin-1 suppresses wound healing and granulation tissue formation in the
      skin of transgenic mice.
AB  - The function of the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1) in
      tissue repair has remained controversial. We established transgenic mice with
      targeted overexpression of TSP-1 in the skin, using a keratin 14 expression
      cassette. TSP-1 transgenic mice were healthy and fertile, and did not show any
      major abnormalities of normal skin vascularity, cutaneous vascular architecture,
      or microvascular permeability. However, healing of full-thickness skin wounds was
      greatly delayed in TSP-1 transgenic mice and was associated with reduced
      granulation tissue formation and highly diminished wound angiogenesis. Moreover,
      TSP-1 potently inhibited fibroblast migration in vivo and in vitro. These
      findings demonstrate that TSP-1 preferentially interfered with wound healing
      associated angiogenesis, rather than with the angiogenesis associated with normal
      development and skin homeostasis, and suggest that therapeutic application of
      angiogenesis inhibitors might potentially be associated with impaired wound
      vascularization and tissue repair.

PMID- 10880441
TI  - Caenorhabditis elegans SOS-1 is necessary for multiple RAS-mediated developmental
      signals.
AB  - Vulval induction in Caenorhabditis elegans has helped define an evolutionarily
      conserved signal transduction pathway from receptor tyrosine kinases (RTKs)
      through the adaptor protein SEM-5 to RAS. One component present in other
      organisms, a guanine nucleotide exchange factor for Ras, has been missing in
      C.ELEGANS: To understand the regulation of this pathway it is crucial to have all
      positive-acting components in hand. Here we describe the identification, cloning
      and genetic characterization of C.ELEGANS: SOS-1, a putative guanine nucleotide
      exchanger for LET-60 RAS. RNA interference experiments suggest that SOS-1
      participates in RAS-dependent signaling events downstream of LET-23 EGFR, EGL-15
      FGFR and an unknown RTK. We demonstrate that the previously identified let-341
      gene encodes SOS-1. Analyzing vulval development in a let-341 null mutant, we
      find an SOS-1-independent pathway involved in the activation of RAS signaling.
      This SOS-1-independent signaling is not inhibited by SLI-1/Cbl and is not
      mediated by PTP-2/SHP, raising the possibility that there could be another
      RasGEF.

PMID- 10880442
TI  - Phagocytosis reveals a reversible differentiated state early in the development
      of the mouse embryo.
AB  - Mural trophectoderm cells of the mouse embryo possess a phagocytic potential as
      early as 3.5 days post coitum (d.p.c.). This first differentiated function shows
      a graded variation along the embryonic-abembryonic axis, from a maximal activity
      in the non-dividing cells of the abembryonic pole to a complete lack of activity
      in the replicating polar trophectoderm overlying the inner cell mass (ICM). This
      pattern can be explained by a negative control exerted by the ICM. Addition of
      FGF4, a factor secreted by ICM cells, strongly inhibited phagocytosis while
      inducing resumption of DNA synthesis in mural trophectoderm cells, revealing a
      reversible, FGF4-dependent differentiation state. Under conditions in which a
      small cluster of mural trophectoderm cells (<10) had internalized large
      particles, these otherwise morphologically normal embryos could not implant in
      the uterus, indicating that cells at the abembryonic pole have a critical role in
      initiating the implantation process. At post-implantation stages (6.5-8.5
      d.p.c.), the ectoplacental cone and secondary giant cells derived from the polar
      trophectoderm also contained active phagocytes, but at that stage,
      differentiation was not reversed by FGF4.

PMID- 10880443
TI  - CD40 signaling in human dendritic cells is initiated within membrane rafts.
AB  - Despite CD40's role in stimulating dendritic cells (DCs) for efficient specific T
      cell stimulation, its signal transduction components in DCs are still poorly
      documented. We show that CD40 receptors on human monocyte-derived DCs associate
      with sphingolipid- and cholesterol-rich plasma membrane microdomains, termed
      membrane rafts. Following engagement, CD40 utilizes membrane raft-associated Lyn
      Src family kinase, and possibly other raft-associated Src family kinases, to
      initiate tyrosine phosphorylation of intracellular substrates. CD40 engagement
      also leads to a membrane raft-restricted recruitment of tumor necrosis factor
      (TNF) receptor-associated factor (TRAF) 3 and, to a lesser extent, TRAF2, to
      CD40's cytoplasmic tail. Thus, the membrane raft structure plays an integral role
      in proximal events of CD40 signaling in DCs. We demonstrate that stimulation of
      Src family kinase within membrane rafts initiates a pathway implicating ERK
      activation, which leads to interleukin (IL)-1alpha/beta and IL-1Ra mRNA
      production and contributes to p38-dependent IL-12 mRNA production. These results
      provide the first evidence that membrane rafts play a critical role in initiation
      of CD40 signaling in DCs, and delineate the outcome of CD40-mediated pathways on
      cytokine production.

PMID- 10880444
TI  - BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for
      receptor BMPR-II.
AB  - Bone morphogenetic protein-2 (BMP-2) induces bone formation and regeneration in
      adult vertebrates and regulates important developmental processes in all animals.
      BMP-2 is a homodimeric cysteine knot protein that, as a member of the
      transforming growth factor-beta (TGF-beta) superfamily, signals by oligomerizing
      type I and type II receptor serine-kinases in the cell membrane. The binding
      epitopes of BMP-2 for BMPR-IA (type I) and BMPR-II or ActR-II (type II) were
      characterized using BMP-2 mutant proteins for analysis of interactions with
      receptor ectodomains. A large epitope 1 for high-affinity BMPR-IA binding was
      detected spanning the interface of the BMP-2 dimer. A smaller epitope 2 for the
      low-affinity binding of BMPR-II was found to be assembled by determinants of a
      single monomer. Symmetry-related pairs of the two juxtaposed epitopes occur near
      the BMP-2 poles. Mutations in both epitopes yielded variants with reduced
      biological activity in C2C12 cells; however, only epitope 2 variants behaved as
      antagonists partially or completely inhibiting BMP-2 activity. These findings
      provide a framework for the molecular description of receptor recognition and
      activation in the BMP/TGF-beta superfamily.

PMID- 10880445
TI  - The apoptotic signaling pathway activated by Toll-like receptor-2.
AB  - The innate immune system uses Toll family receptors to signal for the presence of
      microbes and initiate host defense. Bacterial lipoproteins (BLPs), which are
      expressed by all bacteria, are potent activators of Toll-like receptor-2 (TLR2).
      Here we show that the adaptor molecule, myeloid differentiation factor 88
      (MyD88), mediates both apoptosis and nuclear factor-kappaB (NF-kappaB) activation
      by BLP-stimulated TLR2. Inhibition of the NF-kappaB pathway downstream of MyD88
      potentiates apoptosis, indicating that these two pathways bifurcate at the level
      of MyD88. TLR2 signals for apoptosis through MyD88 via a pathway involving Fas
      associated death domain protein (FADD) and caspase 8. Moreover, MyD88 binds FADD
      and is sufficient to induce apoptosis. These data indicate that TLR2 is a novel
      'death receptor' that engages the apoptotic machinery without a conventional
      cytoplasmic death domain. Through TLR2, BLP induces the synthesis of the
      precursor of the pro-inflammatory cytokine interleukin-1beta (IL-1beta).
      Interestingly, BLP also activates caspase 1 through TLR2, resulting in
      proteolysis and secretion of mature IL-1beta. These results indicate that caspase
      activation is an innate immune response to microbial pathogens, culminating in
      apoptosis and cytokine production.

PMID- 10880446
TI  - Constitutive activation of NF-kappaB and T-cell leukemia/lymphoma in Notch3
      transgenic mice.
AB  - The multiplicity of Notch receptors raises the question of the contribution of
      specific isoforms to T-cell development. Notch3 is expressed in CD4(-)8(-)
      thymocytes and is down-regulated across the CD4(-)8(-) to CD4(+)8(+) transition,
      controlled by pre-T-cell receptor signaling. To determine the effects of Notch3
      on thymocyte development, transgenic mice were generated, expressing lck promoter
      driven intracellular Notch3. Thymuses of young transgenics showed an increased
      number of thymocytes, particularly late CD4(-)8(-) cells, a failure to down
      regulate CD25 in post-CD4(-)8(-) subsets and sustained activity of NF-kappaB.
      Subsequently, aggressive multicentric T-cell lymphomas developed with high
      penetrance. Tumors sustained characteristics of immature thymocytes, including
      expression of CD25, pTalpha and activated NF-kappaB via IKKalpha-dependent
      degradation of IkappaBalpha and enhancement of NF-kappaB-dependent anti-apoptotic
      and proliferative pathways. Together, these data identify activated Notch3 as a
      link between signals leading to NF-kappaB activation and T-cell tumorigenesis.
      The phenotypes of pre-malignant thymocytes and of lymphomas indicate a novel and
      particular role for Notch3 in co-ordinating growth and differentiation of
      thymocytes, across the pre-T/T cell transition, consistent with the normal
      expression pattern of Notch3.

PMID- 10880447
TI  - Circadian clock-protein expression in cyanobacteria: rhythms and phase setting.
AB  - The cyanobacterial gene cluster kaiABC encodes three essential circadian clock
      proteins: KaiA, KaiB and KaiC. The KaiB and KaiC protein levels are robustly
      rhythmical, whereas the KaiA protein abundance undergoes little if any circadian
      oscillation in constant light. The level of the KaiC protein is crucial for
      correct functioning of the clock because induction of the protein at phases when
      the protein level is normally low elicits phase resetting. Titration of the
      effects of the inducer upon phase resetting versus KaiC level shows a direct
      correlation between induction of the KaiC protein within the physiological range
      and significant phase shifting. The protein synthesis inhibitor chloramphenicol
      prevents the induction of KaiC and blocks phase shifting. When the metabolism is
      repressed by either translational inhibition or constant darkness, the rhythm of
      KaiC abundance persists; therefore, clock protein expression has a preferred
      status under a variety of conditions. These data indicate that rhythmic
      expression of KaiC appears to be a crucial component of clock precession in
      cyanobacteria.

PMID- 10880448
TI  - Destabilization of nucleosomes by an unusual DNA conformation adopted by poly(dA)
      small middle dotpoly(dT) tracts in vivo.
AB  - Poly(dA) small middle dotpoly(dT) tracts are common and often found upstream of
      genes in eukaryotes. It has been suggested that poly(dA) small middle dotpoly(dT)
      promotes transcription in vivo by affecting nucleosome formation. On the other
      hand, in vitro studies show that poly(dA) small middle dotpoly(dT) can be easily
      incorporated into nucleosomes. Therefore, the roles of these tracts in nucleosome
      organization in vivo remain to be established. We have developed an assay system
      that can evaluate nucleosome formation in yeast cells, and demonstrated that
      relatively longer tracts such as A(15)TATA(16) and A(34) disrupt an array of
      positioned nucleosomes, whereas a shorter A(5)TATA(4) tract is incorporated in
      positioned nucleosomes of yeast minichromosomes. Thus, nucleosomes are
      destabilized by poly(dA) small middle dotpoly(dT) in vivo in a length-dependent
      manner. Furthermore, in vivo UV footprinting revealed that the longer tracts
      adopt an unusual DNA structure in yeast cells that corresponds to the B'
      conformation described in vitro. Our results support a mechanism in which a
      unique poly(dA) small middle dot poly(dT) conformation presets chromatin
      structure to which transcription factors are accessible.

PMID- 10880449
TI  - The Nac2 gene of Chlamydomonas encodes a chloroplast TPR-like protein involved in
      psbD mRNA stability.
AB  - The psbD mRNA, which encodes the D2 reaction center polypeptide of photosystem
      II, is one of the most abundant chloroplast mRNAs. We have used genomic
      complementation to isolate the nuclear Nac2 gene, which is required for the
      stable accumulation of the psbD mRNA in Chlamydomonas reinhardtii. Nac2 encodes a
      hydrophilic polypeptide of 1385 amino acids with nine tetratricopeptide-like
      repeats (TPRs) in its C-terminal half. Cell fractionation studies indicate that
      the Nac2 protein is localized in the stromal compartment of the chloroplast. It
      is part of a high molecular weight complex that is associated with non-polysomal
      RNA. Change of a conserved alanine residue of the fourth TPR motif by site
      directed mutagenesis leads to aggregation of Nac2 protein and completely
      abrogates its function, indicating that this TPR is important for proper folding
      of the protein and for psbD mRNA stability, processing and/or translation.

PMID- 10880450
TI  - HuCHRAC, a human ISWI chromatin remodelling complex contains hACF1 and two novel
      histone-fold proteins.
AB  - Chromatin remodelling complexes containing the nucleosome-dependent ATPase ISWI
      were first isolated from Drosophila embryos (NURF, CHRAC and ACF). ISWI was the
      only common component reported in these complexes. Our purification of human
      CHRAC (HuCHRAC) shows that ISWI chromatin remodelling complexes can have a
      conserved subunit composition in completely different cell types, suggesting a
      conserved function of ISWI. We show that the human homologues of two novel
      putative histone-fold proteins in Drosophila CHRAC are present in HuCHRAC. The
      two human histone-fold proteins form a stable complex that binds naked DNA but
      not nucleosomes. HuCHRAC also contains human ACF1 (hACF1), the homologue of Acf1,
      a subunit of Drosophila ACF. The N-terminus of mouse ACF1 was reported as a
      heterochromatin-targeting domain. hACF1 is a member of a family of proteins with
      a related domain structure that all may target heterochromatin. We discuss a
      possible function for HuCHRAC in heterochromatin dynamics. HuCHRAC does not
      contain topoisomerase II, which was reported earlier as a subunit of Drosophila
      CHRAC.

PMID- 10880451
TI  - Two RING finger proteins mediate cooperation between ubiquitin-conjugating
      enzymes in DNA repair.
AB  - Two ubiquitin-conjugating enzymes, RAD6 and the heteromeric UBC13-MMS2 complex,
      have been implicated in post-replicative DNA damage repair in yeast. Here we
      provide a mechanistic basis for cooperation between the two enzymes. We show that
      two chromatin-associated RING finger proteins, RAD18 and RAD5, play a central
      role in mediating physical contacts between the members of the RAD6 pathway. RAD5
      recruits the UBC13-MMS2 complex to DNA by means of its RING finger domain.
      Moreover, RAD5 association with RAD18 brings UBC13-MMS2 into contact with the
      RAD6-RAD18 complex. Interaction between the two RING finger proteins thus
      promotes the formation of a heteromeric complex in which the two distinct
      ubiquitin-conjugating activities of RAD6 and UBC13-MMS2 can be closely
      coordinated. Surprisingly, UBC13 and MMS2 are largely cytosolic proteins, but DNA
      damage triggers their redistribution to the nucleus. These findings suggest a
      mechanism by which the activity of this DNA repair pathway could be regulated.

PMID- 10880452
TI  - Sister chromatid gene conversion is a prominent double-strand break repair
      pathway in mammalian cells.
AB  - In mammalian cells, repair of DNA double-strand breaks (DSBs) occurs by both
      homologous and non-homologous mechanisms. By definition, homologous recombination
      requires a template with sufficient sequence identity to the damaged molecule in
      order to direct repair. We now show that the sister chromatid acts as a repair
      template in a substantial proportion of DSB repair events. The outcome of sister
      chromatid repair is primarily gene conversion unassociated with reciprocal
      exchange. This contrasts with expectations from the classical DSB repair model
      originally proposed for yeast meiotic recombination, but is consistent with
      models in which recombination is coupled intimately with replication. These
      results may explain why cytologically observable sister chromatid exchanges are
      induced only weakly by DNA-damaging agents that cause strand breaks, since most
      homologous repair events would not be observed. A preference for non-crossover
      events between sister chromatids suggests that crossovers, although genetically
      silent, may be disfavored for other reasons. Possibly, a general bias against
      crossing over in mitotic cells exists to reduce the potential for genome
      alterations when other homologous repair templates are utilized.

PMID- 10880453
TI  - Evidence for short-patch mismatch repair in Saccharomyces cerevisiae.
AB  - Recombination events between non-identical sequences most often involve
      heteroduplex DNA intermediates that are subjected to mismatch repair. The well
      characterized long-patch mismatch repair process, controlled in eukaryotes by
      bacterial MutS and MutL orthologs, is the major system involved in repair of
      mispaired bases. Here we present evidence for an alternative short-patch mismatch
      repair pathway that operates on a broad spectrum of mismatches. In msh2 mutants
      lacking the long-patch repair system, sequence analysis of recombination tracts
      resulting from exchanges between similar but non-identical (homeologous) parental
      DNAs showed the occurrence of short-patch repair events that can involve <12
      nucleotides. Such events were detected both in mitotic and in meiotic
      recombinants. Confirming the existence of a distinct short-patch repair activity,
      we found in a recombination assay involving homologous alleles that closely
      spaced mismatches are repaired independently with high efficiency in cells
      lacking MSH2 or PMS1. We show that this activity does not depend on genes
      required for nucleotide excision repair and thus differs from the short-patch
      mismatch repair described in Schizosaccharomyces pombe.

PMID- 10880454
TI  - A ring-opening mechanism for DNA binding in the central channel of the T7
      helicase-primase protein.
AB  - We have investigated the mechanism of binding single-stranded DNA (ssDNA) into
      the central channel of the ring-shaped T7 gp4A' helicase-primase hexamer.
      Presteady-state kinetic studies show a facilitated five-step mechanism and
      provide understanding of how a ring-shaped helicase can be loaded on the DNA
      during the initiation of replication. The effect of a primase recognition
      sequence on the observed kinetics suggests that binding to the helicase DNA
      binding site is facilitated by transient binding to the primase DNA-binding site,
      which is proposed to be a loading site. The proposed model involves the fast
      initial binding of the DNA to the primase site on the outside of the helicase
      ring, a fast conformational change, a ring-opening step, migration of the DNA
      into the central channel of the helicase ring, and ring closure. Although an
      intermediate protein-DNA complex is kinetically stable, only the last species in
      the five-step mechanism is poised to function as a helicase at the unwinding
      junction.

PMID- 10880455
TI  - Possible association of BLM in decreasing DNA double strand breaks during DNA
      replication.
AB  - Bloom's syndrome (BS) is a rare genetic disorder and the cells from BS patients
      show genomic instability and an increased level of sister chromatid exchange
      (SCE). We generated BLM(-/-) and BLM(-/-)/RAD54(-/-) DT40 cells from the chicken
      B-lymphocyte line DT40. The BLM(-/-) DT40 cells showed higher sensitivity to
      methyl methanesulfonate and elevated levels of SCE as expected. The targeted
      integration frequency was also increased remarkably in BLM(-/-) cells. The SCE
      frequency increase in BLM(-/-) cells was considerably reduced and the enhanced
      targeted integration observed in BLM(-/-) cells was almost completely abolished
      in BLM(-/-)/RAD54(-/-) cells, indicating that a large portion of the SCE in BLM(
      /-) cells occurs via homologous recombination, and homologous recombination
      events increase with the defect of BLM function. The BLM(-/-)/RAD54(-/-) cells
      showed a slow growth phenotype and an increased incidence of chromosome-type
      breaks/gaps while each single mutant showed relatively small numbers of
      chromosome-type breaks/gaps.

PMID- 10880456
TI  - Efficient intracellular retrotransposition of an exogenous primate retrovirus
      genome.
AB  - The foamy virus (FV) subgroup of Retroviridae reverse transcribe their RNA (pre
      )genome late in the replication cycle before leaving an infected cell. We studied
      whether a marker gene-transducing FV vector is able to shuttle to the nucleus and
      integrate into host cell genomic DNA. While a potential intracellular
      retrotransposition of vectors derived from other retroviruses was below the
      detection limit of our assay, we found that up to 5% of cells transfected with
      the FV vector were stably transduced, harboring 1 to approximately 10 vector
      integrants. Generation of the integrants depended on expression of functional
      capsid, reverse transcriptase and integrase proteins, and did not involve an
      extracellular step. PCR analysis of the U3 region of the 5' long terminal repeat
      and determination of proviral integration sites showed that a reverse
      transcription step had taken place to generate the integrants. Co-expression of a
      mutated envelope allowing particle egress and avoiding extracellular infection
      resulted in a significantly increased rescue of cells harboring integrants,
      suggesting that accumulation of proviruses via intracellular retrotransposition
      represents an integral part of the FV replication strategy.

PMID- 10880457
TI  - Isolation and characterization of Tn7 transposase gain-of-function mutants: a
      model for transposase activation.
AB  - Tn7 transposition has been hypothesized to require a heteromeric transposase
      formed by two Tn7-encoded proteins, TnsA and TnsB, and accessory proteins that
      activate the transposase when they are associated with an appropriate target DNA.
      This study investigates the mechanism of Tn7 transposase activation by isolation
      and analysis of transposase gain-of-function mutants that are active in the
      absence of these accessory proteins. This work shows directly that TnsA and TnsB
      are essential and sufficient components of the Tn7 transposase and also provides
      insight into the signals that activate the transposase. We also describe a
      protein-protein interaction between TnsA and TnsC, a regulatory accessory
      protein, that is likely to be critical for transposase activation.

PMID- 10880458
TI  - Arginines 29 and 59 of elongation factor G are important for GTP hydrolysis or
      translocation on the ribosome.
AB  - GTP hydrolysis by elongation factor G (EF-G) is essential for the translocation
      step in protein elongation. The low intrinsic GTPase activity of EF-G is strongly
      stimulated by the ribosome. Here we show that a conserved arginine, R29, of
      Escherichia coli EF-G is crucial for GTP hydrolysis on the ribosome, but not for
      GTP binding or ribosome interaction, suggesting that it may be directly involved
      in catalysis. Another conserved arginine, R59, which is homologous to the
      catalytic arginine of G(alpha) proteins, is not essential for GTP hydrolysis, but
      influences ribosome binding and translocation. These results indicate that EF-G
      is similar to other GTPases in that an arginine residue is required for GTP
      hydrolysis, although the structural changes leading to GTPase activation are
      different.

PMID- 10880459
TI  - Adenovirus-specific translation by displacement of kinase Mnk1 from cap
      initiation complex eIF4F.
AB  - Translation of cellular mRNAs involves formation of a cap-binding translation
      initiation complex known as eIF4F, containing phosphorylated cap-binding protein
      eIF4E, eIF4E kinase Mnk1, eIF4A, poly(A)-binding protein and eIF4G. Adenovirus is
      shown to prevent cellular translation by displacing Mnk1 from eIF4F, thereby
      blocking phosphorylation of eIF4E. Over expression of an eIF4E mutant that cannot
      be phosphorylated by Mnk1 impairs translation of cellular but not viral late
      mRNAs. Adenovirus 100k protein is shown to bind the C-terminus of eIF4G in vivo
      and in vitro, the same region bound by Mnk1. In vivo, 100k protein displaces Mnk1
      from eIF4G during adenovirus infection, or in transfected cells. Purified 100k
      protein also evicts Mnk1 from isolated eIF4F complexes in vitro. A mutant
      adenovirus with a temperature-sensitive 100k protein that cannot inhibit cellular
      protein synthesis at restrictive temperature no longer blocks Mnk1 binding to
      eIF4G, or phosphorylation of eIF4E. We describe a mechanism whereby adenovirus
      selectively inhibits the translation of cellular but not viral mRNAs by
      displacement of Mnk1 from eIF4G and inhibition of eIF4E phosphorylation.

PMID- 10880460
TI  - Covalent modifier NEDD8 is essential for SCF ubiquitin-ligase in fission yeast.
AB  - A ubiquitin-like modifier, NEDD8, is covalently attached to cullin-family
      proteins, but its physiological role is poorly understood. Here we report that
      the NEDD8-modifying pathway is essential for cell viability and function of Pcu1
      (cullin-1 orthologue) in fission yeast. Pcu1 assembled on SCF ubiquitin-ligase
      was completely modified by NEDD8. Pcu1(K713R) defective for NEDD8 conjugation
      lost the ability to complement lethality due to pcu1 deletion. Forced expression
      of Pcu1(K713R) or depletion of NEDD8 in cells resulted in impaired cell
      proliferation and marked stabilization of the cyclin-dependent kinase inhibitor
      Rum1, which is a substrate of the SCF complex. Based on these findings, we
      propose that covalent modification of cullin-1 by the NEDD8 system plays an
      essential role in the function of SCF in fission yeast.

PMID- 10880461
TI  - A geminivirus replication protein interacts with the retinoblastoma protein
      through a novel domain to determine symptoms and tissue specificity of infection
      in plants.
AB  - Geminiviruses replicate in nuclei of mature plant cells after inducing the
      accumulation of host DNA replication machinery. Earlier studies showed that the
      viral replication factor, AL1, is sufficient for host induction and interacts
      with the cell cycle regulator, retinoblastoma (pRb). Unlike other DNA virus
      proteins, AL1 does not contain the pRb binding consensus, LXCXE, and interacts
      with plant pRb homo logues (pRBR) through a novel amino acid sequence. We mapped
      the pRBR binding domain of AL1 between amino acids 101 and 180 and identified two
      mutants that are differentially impacted for AL1-pRBR interactions. Plants
      infected with the E-N140 mutant, which is wild-type for pRBR binding, developed
      wild-type symptoms and accumulated viral DNA and AL1 protein in epidermal,
      mesophyll and vascular cells of mature leaves. Plants inoculated with the KEE146
      mutant, which retains 16% pRBR binding activity, only developed chlorosis along
      the veins, and viral DNA, AL1 protein and the host DNA synthesis factor,
      proliferating cell nuclear antigen, were localized to vascular tissue. These
      results established the importance of AL1-pRBR interactions during geminivirus
      infection of plants.

PMID- 10880462
TI  - Limited overlapping roles of P15(INK4b) and P18(INK4c) cell cycle inhibitors in
      proliferation and tumorigenesis.
AB  - Entry of quiescent cells into the cell cycle is driven by the cyclin D-dependent
      kinases Cdk4 and Cdk6. These kinases are negatively regulated by the INK4 cell
      cycle inhibitors. We report the generation of mice defective in P15(INK4b) and
      P18(INK4c). Ablation of these genes, either alone or in combination, does not
      abrogate cell contact inhibition or senescence of mouse embryo fibroblasts in
      culture. However, loss of P15(INK4b), but not of P18(INK4c), confers
      proliferative advantage to these cells and makes them more sensitive to
      transformation by H-ras oncogenes. In vivo, ablation of P15(INK4b) and P18(INK4c)
      genes results in lymphoproliferative disorders and tumor formation. Mice lacking
      P18(INK4c) have deregulated epithelial cell growth leading to the formation of
      cysts, mostly in the cortical region of the kidneys and the mammary epithelium.
      Loss of both P15(INK4b) and P18(INK4c) does not result in significantly distinct
      phenotypic manifestations except for the appearance of cysts in additional
      tissues. These results indicate that P15(INK4b) and P18(IKN4c) are tumor
      suppressor proteins that act in different cellular lineages and/or pathways with
      limited compensatory roles.

PMID- 10880463
TI  - Karl Landsteiner and the first human marker locus.

PMID- 10880464
TI  - Cats as an aid to teaching genetics.
AB  - I have used an exercise involving domestic cats in the General Genetics course at
      the University of Nebraska-Lincoln for the past 5 years. Using a coherent set of
      traits in an organism familiar to the students makes it easy to illustrate
      principles of transmission and population genetics. The one-semester course
      consists primarily of sophomores and juniors who have either taken a one-semester
      introductory biology course, a one-semester cell biology course, or have a strong
      high school biology background. The students are given a handout and asked to
      determine the genotype at seven unlinked loci of at least one cat. To fill out
      the form, the students have to grasp such concepts as dominance, incomplete
      dominance, temperature-sensitive mutations, epistatic interactions, sex linkage,
      and variable expressivity. Completing the form reinforces these concepts as they
      observe the cat's phenotype and fill in the genotype. I then analyze the
      collected data and use it in my lectures on population genetics to illustrate the
      Hardy-Weinberg equilibrium, calculate allele frequencies, and use statistics.
      This allows the students to look at population genetics in a very positive light
      and provides concrete examples of some often misunderstood principles.

PMID- 10880465
TI  - Defects in protein glycosylation cause SHO1-dependent activation of a STE12
      signaling pathway in yeast.
AB  - In haploid Saccharomyces cerevisiae, mating occurs by activation of the pheromone
      response pathway. A genetic selection for mutants that activate this pathway
      uncovered a class of mutants defective in cell wall integrity. Partial loss-of
      function alleles of PGI1, PMI40, PSA1, DPM1, ALG1, MNN10, SPT14, and OCH1, genes
      required for mannose utilization and protein glycosylation, activated a pheromone
      response-pathway-dependent reporter (FUS1) in cells lacking a basal signal
      (ste4). Pathway activation was suppressed by the addition of mannose to hexose
      isomerase mutants pgi1-101 and pmi40-101, which bypassed the requirement for
      mannose biosynthesis in these mutants. Pathway activation was also suppressed in
      dpm1-101 mutants by plasmids that contained RER2 or PSA1, which produce the
      substrates for Dpm1. Activation of FUS1 transcription in the mannose
      utilization/protein glycosylation mutants required some but not all proteins from
      three different signaling pathways: the pheromone response, invasive growth, and
      HOG pathways. We specifically suggest that a Sho1 --> Ste20/Ste50 --> Ste11 -->
      Ste7 --> Kss1 --> Ste12 pathway is responsible for activation of FUS1
      transcription in these mutants. Because loss of pheromone response pathway
      components leads to a synthetic growth defect in mannose utilization/protein
      glycosylation mutants, we suggest that the Sho1 --> Ste12 pathway contributes to
      maintenance of cell wall integrity in vegetative cells.

PMID- 10880466
TI  - The Saccharomyces cerevisiae RDN1 locus is sequestered from interchromosomal
      meiotic ectopic recombination in a SIR2-dependent manner.
AB  - Meiotic ectopic recombination occurs at similar frequencies among many sites in
      the yeast genome, suggesting that all loci are similarly accessible to homology
      searching. In contrast, we found that his3 sequences integrated in the RDN1
      (rDNA) locus were unusually poor participants in meiotic recombination with his3
      sequences at other sites. We show that the low rate of meiotic ectopic
      recombination resulted from the poor ability of RDN1::his3 to act as a donor
      sequence. SIR2 partially repressed interchromosomal meiotic ectopic recombination
      at RDN1, consistent with its role in regulating recombination, gene expression,
      and retrotransposition within RDN1. We propose that RDN1 is physically
      sequestered from meiotic homology searching mechanisms.

PMID- 10880467
TI  - Isolation and characterization of HRT1 using a genetic screen for mutants unable
      to degrade Gic2p in saccharomyces cerevisiae.
AB  - Skp1p-cullin-F-box (SCF) protein complexes are ubiquitin ligases required for
      degradation of many regulatory proteins involved in cell cycle progression,
      morphogenesis, and signal transduction. Using a genetic screen, we have isolated
      a novel allele of the HRT1/RBX1 gene in budding yeast (hrt1-C81Y). hrt1-C81Y
      mutant cells exhibited an aberrant morphology but were viable at all
      temperatures. The cells displayed multiple genetic interactions with mutations in
      known SCF components and were defective for the degradation of several SCF
      targets including Gic2p, Far1p, Sic1p, and Cln2p. In addition, they also failed
      to degrade the F-box proteins Grr1p, Cdc4p, and Met30p. Wild-type Hrt1p but not
      Hrt1p-C81Y was able to bind multiple F-box proteins in an F-box-dependent manner.
      Hrt1p-C81Y harbors a single mutation in its ring-finger domain, which is
      conserved in subunits of distinct E3 ligases. Finally, Hrt1p was localized in
      both nucleus and cytoplasm and despite a short half-life was expressed
      constitutively throughout the cell cycle. Taken together, these results suggest
      that Hrt1p is a core subunit of multiple SCF complexes.

PMID- 10880468
TI  - Functional interaction of CCR4-NOT proteins with TATAA-binding protein (TBP) and
      its associated factors in yeast.
AB  - The CCR4-NOT transcriptional regulatory complex affects expression of a number of
      genes both positively and negatively. We report here that components of the CCR4
      NOT complex functionally and physically interact with TBP and TBP-associated
      factors. First, mutations in CCR4-NOT components suppressed the his4-912delta
      insertion in a manner similar to that observed for the defective TBP allele spt15
      122. Second, using modified HIS3 promoter derivatives containing specific
      mutations within the TATA sequence, we found that the NOT proteins were general
      repressors that disrupt TBP function irrespective of the DNA sequence. Third,
      increasing the dosage of NOT1 specifically inhibited the ability of spt15-122 to
      suppress the his4-912delta insertion but did not affect the Spt- phenotype of
      spt3 or spt10 at this locus. Fourth, spt3, spt8, and spt15-21 alleles (all
      involved in affecting interaction of SPT3 with TBP) suppressed ccr4 and caf1
      defects. Finally, we show that NOT2 and NOT5 can be immunoprecipitated by TBP.
      NOT5 was subsequently shown to associate with TBP and TAFs and this association
      was dependent on the integrity of TFIID. These genetic and physical interactions
      indicate that one role of the CCR4-NOT proteins is to inhibit functional TBP-DNA
      interactions, perhaps by interacting with and modulating the function of TFIID.

PMID- 10880469
TI  - Genetic analyses of Schizosaccharomyces pombe dna2(+) reveal that dna2 plays an
      essential role in Okazaki fragment metabolism.
AB  - In this report, we investigated the phenotypes caused by temperature-sensitive
      (ts) mutant alleles of dna2(+) of Schizosaccharomyces pombe, a homologue of DNA2
      of budding yeast, in an attempt to further define its function in vivo with
      respect to lagging-strand synthesis during the S-phase of the cell cycle. At the
      restrictive temperature, dna2 (ts) cells arrested at late S-phase but were
      unaffected in bulk DNA synthesis. Moreover, they exhibited aberrant mitosis when
      combined with checkpoint mutations, in keeping with a role for Dna2 in Okazaki
      fragment maturation. Similarly, spores in which dna2(+) was disrupted duplicated
      their DNA content during germination and also arrested at late S-phase.
      Inactivation of dna2(+) led to chromosome fragmentation strikingly similar to
      that seen when cdc17(+), the DNA ligase I gene, is inactivated. The temperature
      dependent lethality of dna2 (ts) mutants was suppressed by overexpression of
      genes encoding subunits of polymerase delta (cdc1(+) and cdc27(+)), DNA ligase I
      (cdc17(+)), and Fen-1 (rad2(+)). Each of these gene products plays a role in the
      elongation or maturation of Okazaki fragments. Moreover, they all interacted with
      S. pombe Dna2 in a yeast two-hybrid assay, albeit to different extents. On the
      basis of these results, we conclude that dna2(+) plays a direct role in the
      Okazaki fragment elongation and maturation. We propose that dna2(+) acts as a
      central protein to form a complex with other proteins required to coordinate the
      multienzyme process for Okazaki fragment elongation and maturation.

PMID- 10880470
TI  - MPH1, a yeast gene encoding a DEAH protein, plays a role in protection of the
      genome from spontaneous and chemically induced damage.
AB  - We have characterized the MPH1 gene from Saccharomyces cerevisiae. mph1 mutants
      display a spontaneous mutator phenotype. Homologs were found in archaea and in
      the EST libraries of Drosophila, mouse, and man. Mph1 carries the signature
      motifs of the DEAH family of helicases. Selected motifs were shown to be
      necessary for MPH1 function by introducing missense mutations. Possible indirect
      effects on translation and splicing were excluded by demonstrating nuclear
      localization of the protein and splicing proficiency of the mutant. A mutation
      spectrum did not show any conspicuous deviations from wild type except for an
      underrepresentation of frameshift mutations. The mutator phenotype was dependent
      on REV3 and RAD6. The mutant was sensitive to MMS, EMS, 4-NQO, and camptothecin,
      but not to UV light and X rays. Epistasis analyses were carried out with
      representative mutants from various repair pathways (msh6, mag1, apn1, rad14,
      rad52, rad6, mms2, and rev3). No epistatic interactions were found, either for
      the spontaneous mutator phenotype or for MMS, EMS, and 4-NQO sensitivity. mph1
      slightly increased the UV sensitivity of mms2, rad6, and rad14 mutants, but no
      effect on X-ray sensitivity was observed. These data suggest that MPH1 is not
      part of a hitherto known repair pathway. Possible functions are discussed.

PMID- 10880471
TI  - Physical map of a conditionally dispensable chromosome in Nectria haematococca
      mating population VI and location of chromosome breakpoints.
AB  - Certain isolates of the plant pathogenic fungus Nectria haematococca mating
      population (MP) VI contain a 1.6-Mb conditionally dispensable (CD) chromosome
      carrying the phytoalexin detoxification genes MAK1 and PDA6-1. This chromosome is
      structurally unstable during sexual reproduction. As a first step in our analysis
      of the mechanisms underlying this chromosomal instability, hybridization between
      overlapping cosmid clones was used to construct a map of the MAK1 PDA6-1
      chromosome. The map consists of 33 probes that are linked by 199 cosmid clones.
      The polymerase chain reaction and Southern analysis of N. haematococca MP VI DNA
      digested with infrequently cutting restriction enzymes were used to close gaps
      and order the hybridization-derived contigs. Hybridization to a probe extended
      from telomeric repeats was used to anchor the ends of the map to the actual
      chromosome ends. The resulting map is estimated to cover 95% of the MAK1 PDA6-1
      chromosome and is composed of two ordered contigs. Thirty-eight percent of the
      clones in the minimal map are known to contain repeated DNA sequences. Three
      dispersed repeats were cloned during map construction; each is present in five to
      seven copies on the chromosome. The cosmid clones representing the map were
      probed with deleted forms of the CD chromosome and the results were integrated
      into the map. This allowed the identification of chromosome breakpoints and
      deletions.

PMID- 10880472
TI  - Vegetative incompatibility in the het-6 region of Neurospora crassa is mediated
      by two linked genes.
AB  - Non-self-recognition during asexual growth of Neurospora crassa involves
      restriction of heterokaryon formation via genetic differences at 11 het loci,
      including mating type. The het-6 locus maps to a 250-kbp region of LGIIL. We used
      restriction fragment length polymorphisms in progeny with crossovers in the het-6
      region and a DNA transformation assay to identify two genes in a 25-kbp region
      that have vegetative incompatibility activity. The predicted product of one of
      these genes, which we designate het-6(OR), has three regions of amino acid
      sequence similarity to the predicted product of the het-e vegetative
      incompatibility gene in Podospora anserina and to the predicted product of tol,
      which mediates mating-type vegetative incompatibility in N. crassa. The predicted
      product of the alternative het-6 allele, HET-6(PA), shares only 68% amino acid
      identity with HET-6(OR). The second incompatibility gene, un-24(OR), encodes the
      large subunit of ribonucleotide reductase, which is essential for de novo
      synthesis of DNA. A region in the carboxyl-terminal portion of UN-24 is
      associated with incompatibility and is variable between un-24(OR) and the
      alternative allele un-24(PA). Linkage analysis indicates that the 25-kbp un-24
      het-6 region is inherited as a block, suggesting that a nonallelic interaction
      may occur between un-24 and het-6 and possibly other loci within this region to
      mediate vegetative incompatibility in the het-6 region of N. crassa.

PMID- 10880473
TI  - The cloning and molecular analysis of pawn-B in Paramecium tetraurelia.
AB  - Pawn mutants of Paramecium tetraurelia lack a depolarization-activated Ca(2+)
      current and do not swim backward. Using the method of microinjection and sorting
      a genomic library, we have cloned a DNA fragment that complements pawn-B
      (pwB/pwB). The minimal complementing fragment is a 798-bp open reading frame
      (ORF) that restores the Ca(2+) current and the backward swimming when expressed.
      This ORF contains a 29-bp intron and is transcribed and translated. The
      translated product has two putative transmembrane domains but no clear matches in
      current databases. Mutations in the available pwB alleles were found within this
      ORF. The d4-95 and d4-96 alleles are single base substitutions, while d4-662
      (previously pawn-D) harbors a 44-bp insertion that matches an internal eliminated
      sequence (IES) found in the wild-type germline DNA except for a single C-to-T
      transition. Northern hybridizations and RT-PCR indicate that d4-662 transcripts
      are rapidly degraded or not produced. A second 155-bp IES in the wild-type
      germline ORF excises at two alternative sites spanning three asparagine codons.
      The pwB ORF appears to be separated from a 5' neighboring ORF by only 36 bp. The
      close proximity of the two ORFs and the location of the pwB protein as indicated
      by GFP-fusion constructs are discussed.

PMID- 10880474
TI  - Autonomously replicating macronuclear DNA pieces are the physical basis of
      genetic coassortment groups in Tetrahymena thermophila.
AB  - The macronucleus of the ciliate Tetrahymena thermophila contains a fragmented
      somatic genome consisting of several hundred identifiable chromosome pieces.
      These pieces are generated by site-specific fragmentation of the germline
      chromosomes and most of them are represented at an average of 45 copies per
      macronucleus. In the course of successive divisions of an initially heterozygous
      macronucleus, the random distribution of alleles of loci carried on these copies
      eventually generates macronuclei that are pure for one allele or the other. This
      phenomenon is called phenotypic assortment. We have previously reported the
      existence of loci that assort together (coassort) and hypothesized that these
      loci reside on the same macronuclear piece. The work reported here provides new,
      rigorous genetic support for the hypothesis that macronuclear autonomously
      replicating chromosome pieces are the physical basis of coassortment groups.
      Thus, coassortment allows the mapping of the somatic genome by purely genetic
      means. The data also strongly suggest that the random distribution of alleles in
      the Tetrahymena macronucleus is due to the random distribution of the MAC
      chromosome pieces that carry them.

PMID- 10880475
TI  - Caenorhabditis elegans lin-13, a member of the LIN-35 Rb class of genes involved
      in vulval development, encodes a protein with zinc fingers and an LXCXE motif.
AB  - The SynMuv genes appear to be involved in providing a signal that inhibits vulval
      precursor cells from adopting vulval fates in Caenorhabditis elegans. One group
      of SynMuv genes, termed class B, includes genes encoding proteins related to the
      tumor suppressor Rb and RbAp48, a protein that binds Rb. Here, we provide genetic
      evidence that lin-13 behaves as a class B SynMuv gene. We show that null alleles
      of lin-13 are temperature sensitive and maternally rescued, resulting in
      phenotypes ranging in severity from L2 arrest (when both maternal and zygotic
      activities are removed at 25 degrees ), to sterile Multivulva (when only zygotic
      activity is removed at 25 degrees ), to sterile non-Multivulva (when both
      maternal and zygotic activities are removed at 15 degrees ), to wild-type/class B
      SynMuv (when only zygotic activity is removed at 15 degrees ). We also show that
      LIN-13 is a nuclear protein that contains multiple zinc fingers and a motif,
      LXCXE, that has been implicated in Rb binding. These results together suggest a
      role for LIN-13 in Rb-mediated repression of vulval fates.

PMID- 10880476
TI  - dpy-18 encodes an alpha-subunit of prolyl-4-hydroxylase in caenorhabditis
      elegans.
AB  - Collagen is an extracellular matrix (ECM) component encoded by a large multigene
      family in multicellular animals. Procollagen is post-translationally modified by
      prolyl-4-hydroxylase (EC 1.14.11.2) before secretion and participation in ECM
      formation. Therefore, collagen processing and regulation can be studied by
      examining this required interaction of prolyl-4-hydroxylase with procollagen.
      High-resolution polymorphism mapping was used to place the Caenorhabditis elegans
      dpy-18 gene on the physical map, and we show that it encodes a prolyl-4
      hydroxylase alpha catalytic subunit. The Dpy phenotype of dpy-18(e364) amber
      mutants is more severe when this mutation is in trans to the noncomplementing
      deficiency tDf7, while the dpy-18(e499) deletion mutant exhibits the same
      phenotype as dpy-18(e499)/tDf7. Furthermore, dpy-18 RNA interference (RNAi) in
      wild-type worms results in Dpy progeny, while dpy-18 (RNAi) in dpy-18(e499)
      mutants does not alter the Dpy phenotype of their progeny. These observations
      suggest that the dpy-18 null phenotype is Dpy. A dpy-18::gfp promoter fusion
      construct is expressed throughout the hypodermis within the cells that abundantly
      produce the cuticle collagens, as well as in certain head and posterior neurons.
      While prolyl-4-hydroxylase has been studied extensively by biochemical
      techniques, this is the first report of a mutationally defined prolyl-4
      hydroxylase in any animal.

PMID- 10880478
TI  - Abnormal turning behavior in Drosophila larvae. Identification and molecular
      analysis of scribbler (sbb).
AB  - Our genetic dissection of behavior has isolated scribbler (sbb), a vital gene
      that encodes a novel protein expressed in the embryonic and larval nervous
      systems and in the imaginal discs. Larvae with mutations in sbb exhibit
      abnormally high amounts of turning behavior in the absence of food. sbb is a
      large gene spanning >50 kb of genomic DNA with four major developmentally
      regulated transcripts. Transgenic rescue of scribbler behavior was demonstrated
      by targeting expression of a normal sbb transgene (sbb(+)) expressing one of the
      major transcripts to the nervous system. The vital function of sbb was restored
      by ubiquitous expression of this transgene throughout development.

PMID- 10880477
TI  - RNA editing of the Drosophila para Na(+) channel transcript. Evolutionary
      conservation and developmental regulation.
AB  - Post-transcriptional editing of pre-mRNAs through the action of dsRNA adenosine
      deaminases results in the modification of particular adenosine (A) residues to
      inosine (I), which can alter the coding potential of the modified transcripts. We
      describe here three sites in the para transcript, which encodes the major voltage
      activated Na(+) channel polypeptide in Drosophila, where RNA editing occurs. The
      occurrence of RNA editing at the three sites was found to be developmentally
      regulated. Editing at two of these sites was also conserved across species
      between the D. melanogaster and D. virilis. In each case, a highly conserved
      region was found in the intron downstream of the editing site and this region was
      shown to be complementary to the region of the exonic editing site. Thus, editing
      at these sites would appear to involve a mechanism whereby the edited exon forms
      a base-paired secondary structure with the distant conserved noncoding sequences
      located in adjacent downstream introns, similar to the mechanism shown for A-to-I
      RNA editing of mammalian glutamate receptor subunits (GluRs). For the third site,
      neither RNA editing nor the predicted RNA secondary structures were
      evolutionarily conserved. Transcripts from transgenic Drosophila expressing a
      minimal editing site construct for this site were shown to faithfully undergo RNA
      editing. These results demonstrate that Na(+) channel diversity in Drosophila is
      increased by RNA editing via a mechanism analogous to that described for
      transcripts encoding mammalian GluRs.

PMID- 10880479
TI  - A physical map of the polytenized region (101EF-102F) of chromosome 4 in
      Drosophila melanogaster.
AB  - Chromosome 4, the smallest autosome ( approximately 5 Mb in length) in Drosophila
      melanogaster contains two major regions. The centromeric domain ( approximately 4
      Mb) is heterochromatic and consists primarily of short, satellite repeats. The
      remaining approximately 1.2 Mb, which constitutes the banded region (101E-102F)
      on salivary gland polytene chromosomes and contains the identified genes, is the
      region mapped in this study. Chromosome walking was hindered by the abundance of
      moderately repeated sequences dispersed along the chromosome, so we used many
      entry points to recover overlapping cosmid and BAC clones. In situ hybridization
      of probes from the two ends of the map to polytene chromosomes confirmed that the
      cloned region had spanned the 101E-102F interval. Our BAC clones comprised three
      contigs; one gap was positioned distally in 102EF and the other was located
      proximally at 102B. Twenty-three genes, representing about half of our revised
      estimate of the total number of genes on chromosome 4, were positioned on the BAC
      contigs. A minimal tiling set of the clones we have mapped will facilitate both
      the assembly of the DNA sequence of the chromosome and a functional analysis of
      its genes.

PMID- 10880480
TI  - Joint effects of natural selection and recombination on gene flow between
      Drosophila ananassae populations.
AB  - We estimated DNA sequence variation in a 5.7-kb fragment of the furrowed (fw)
      gene region within and between four populations of Drosophila ananassae; fw is
      located in a chromosomal region of very low recombination. We analyzed gene flow
      between these four populations along a latitudinal transect on the Indian
      subcontinent: two populations from southern, subtropical areas (Hyderabad, India,
      and Sri Lanka) and two from more temperate zones in the north (Nepal and Burma).
      Furthermore, we compared the pattern of differentiation at fw with published data
      from Om(1D), a gene located in a region of normal recombination. While
      differentiation at Om(1D) shows an isolation-by-distance effect, at fw the
      pattern of differentiation is quite different such that the frequencies of single
      nucleotide polymorphisms are homogenized over extended geographic regions (i.e.,
      among the two populations of the northern species range from Burma and Nepal as
      well as among the two southern populations from India and Sri Lanka), but
      strongly differentiated between the northern and southern populations. To examine
      these differences in the patterns of variation and differentiation between the
      Om(1D) and fw gene regions, we determine the critical values of our previously
      proposed test of the background selection hypothesis (henceforth called F(ST)
      test). Using these results, we show that the pattern of differentiation at fw may
      be inconsistent with the background selection model. The data depart from this
      model in a direction that is compatible with the occurrence of recent selective
      sweeps in the northern as well as southern populations.

PMID- 10880482
TI  - Long microsatellite alleles in Drosophila melanogaster have a downward mutation
      bias and short persistence times, which cause their genome-wide
      underrepresentation.
AB  - Microsatellites are short tandemly repeated DNA sequence motifs that are highly
      variable in most organisms. In contrast to mammals, long microsatellites (>15
      repeats) are extremely rare in the Drosophila melanogaster genome. To investigate
      this paucity of long microsatellites in Drosophila, we studied 19 loci with
      exceptionally long microsatellite alleles. Inter- and intraspecific analysis
      showed that long microsatellite alleles arose in D. melanogaster only very
      recently. This lack of old alleles with many repeats indicated that long
      microsatellite alleles have short persistence times. The size distribution of
      microsatellite mutations in mutation-accumulation lines suggests that long
      alleles have a mutation bias toward a reduction in the number of repeat units.
      This bias causes the short persistence times of long microsatellite alleles. We
      propose that species-specific, size-dependent mutation spectra of microsatellite
      alleles may provide a general mechanism to account for the observed differences
      in microsatellite length between species.

PMID- 10880481
TI  - Chromosomal position effects reveal different cis-acting requirements for rDNA
      transcription and sex chromosome pairing in Drosophila melanogaster.
AB  - In Drosophila melanogaster, the rDNA loci function in ribosome biogenesis and
      nucleolar formation and also as sex chromosome pairing sites in male meiosis.
      These activities are not dependent on the heterochromatic location of the rDNA,
      because euchromatic transgenes are competent to form nucleoli and restore pairing
      to rDNA-deficient X chromosomes. These transgene studies, however, do not address
      requirements for the function of the endogenous rDNA loci within the
      heterochromatin. Here we describe two chromosome rearrangements that disrupt rDNA
      functions. Both rearrangements are translocations that cause an extreme bobbed
      visible phenotype and XY nondisjunction and meiotic drive in males. However,
      neither rearrangement interacts with a specific Y chromosome, Ymal(+), that
      induces male sterility in combination with rDNA deletions. Molecular studies show
      that the translocations are not associated with gross rearrangements of the rDNA
      repeat arrays. Rather, suppression of the bobbed phenotypes by Y heterochromatin
      suggests that decreased rDNA function is caused by a chromosomal position effect.
      While both translocations affect rDNA transcription, only one disrupts meiotic XY
      pairing, indicating that there are different cis-acting requirements for rDNA
      transcription and rDNA-mediated meiotic pairing.

PMID- 10880483
TI  - Patterns of variation in the intergenic spacers of ribosomal DNA in Drosophila
      melanogaster support a model for genetic exchanges during X-Y pairing.
AB  - Detailed analysis of variation in intergenic spacer (IGS) and internal
      transcribed spacer (ITS) regions of rDNA drawn from natural populations of
      Drosophila melanogaster has revealed contrasting patterns of homogenization
      although both spacers are located in the same rDNA unit. On the basis of the role
      of IGS regions in X-Y chromosome pairing, we proposed a mechanism of single
      strand exchanges at the IGS regions, which can explain the different evolutionary
      trajectories followed by the IGS and the ITS regions. Here, we provide data from
      the chromosomal distribution of selected IGS length variants, as well as the
      detailed internal structure of a large number of IGS regions obtained from
      specific X and Y chromosomes. The variability found in the different internal
      subrepeat regions of IGS regions isolated from X and Y chromosomes supports the
      proposed mechanism of genetic exchanges and suggests that only the "240"
      subrepeats are involved. The presence of a putative site for topoisomerase I at
      the 5' end of the 18S rRNA gene would allow for the exchange between X and Y
      chromosomes of some 240 subrepeats, the promoter, and the ETS region, leaving the
      rest of the rDNA unit to evolve along separate chromosomal lineages. The
      phenomenon of localized units (modules) of homogenization has implications for
      multigene family evolution in general.

PMID- 10880484
TI  - Ariadne-1: a vital Drosophila gene is required in development and defines a new
      conserved family of ring-finger proteins.
AB  - We report the identification and functional characterization of ariadne-1 (ari
      1), a novel and vital Drosophila gene required for the correct differentiation of
      most cell types in the adult organism. Also, we identify a sequence-related gene,
      ari-2, and the corresponding mouse and human homologues of both genes. All these
      sequences define a new protein family by the Acid-rich, RING finger, B-box, RING
      finger, coiled-coil (ARBRCC) motif string. In Drosophila, ari-1 is expressed
      throughout development in all tissues. The mutant phenotypes are most noticeable
      in cells that undergo a large and rapid membrane deposition, such as rewiring
      neurons during metamorphosis, large tubular muscles during adult myogenesis, and
      photoreceptors. Occasional survivors of null alleles exhibit reduced life span,
      motor impairments, and short and thin bristles. Single substitutions at key
      cysteines in each RING finger cause lethality with no survivors and a drastic
      reduction of rough endoplasmic reticulum that can be observed in the
      photoreceptors of mosaic eyes. In yeast two-hybrid assays, the protein ARI-1
      interacts with a novel ubiquitin-conjugating enzyme, UbcD10, whose sequence is
      also reported here. The N-terminal RING-finger motif is necessary and sufficient
      to mediate this interaction. Mouse and fly homologues of both ARI proteins and
      the Ubc can substitute for each other in the yeast two-hybrid assay, indicating
      that ARI represents a conserved novel mechanism in development. In addition to
      ARI homologues, the RBR signature is also found in the Parkinson-disease-related
      protein Parkin adjacent to an ubiquitin-like domain, suggesting that the study of
      this mechanism could be relevant for human pathology.

PMID- 10880485
TI  - Nucleotide polymorphism at the RpII215 gene in Drosophila subobscura. Weak
      selection on synonymous mutations.
AB  - Nucleotide variation in an 8.1-kb fragment encompassing the RpII215 gene, which
      encodes the largest subunit of the RNA polymerase II complex, is analyzed in a
      sample of 11 chromosomes from a natural population of Drosophila subobscura. No
      amino acid polymorphism was detected among the 157 segregating sites. The
      observed numbers of preferred and unpreferred derived synonymous mutations can be
      explained by neutral mutational processes. In contrast, preferred mutations
      segregate at significantly higher frequency than unpreferred mutations,
      suggesting the action of natural selection. The polymorphism to divergence ratio
      is different for preferred and unpreferred changes, in agreement with their
      beneficial and deleterious effects on fitness, respectively. Preferred and
      unpreferred codons are nonrandomly distributed in the RpII215 gene, leading to a
      heterogeneous distribution of polymorphic to fixed synonymous differences across
      this coding region. This intragenic variation of the polymorphism/divergence
      ratio cannot be explained by different patterns of gene expression, mutation, or
      recombination rates, and therefore it indicates that selection coefficients for
      synonymous mutations can vary extensively across a coding region. The application
      of nucleotide composition stationarity tests in coding and flanking noncoding
      regions, assumed to behave neutrally, allows the detection of the action of
      natural selection when stationarity holds in the noncoding region.

PMID- 10880486
TI  - Genetic analysis demonstrates a direct link between rho signaling and nonmuscle
      myosin function during Drosophila morphogenesis.
AB  - A dynamic actomyosin cytoskeleton drives many morphogenetic events. Conventional
      nonmuscle myosin-II (myosin) is a key chemomechanical motor that drives
      contraction of the actin cytoskeleton. We have explored the regulation of myosin
      activity by performing genetic screens to identify gene products that collaborate
      with myosin during Drosophila morphogenesis. Specifically, we screened for second
      site noncomplementors of a mutation in the zipper gene that encodes the nonmuscle
      myosin-II heavy chain. We determined that a single missense mutation in the
      zipper(Ebr) allele gives rise to its sensitivity to second-site
      noncomplementation. We then identify the Rho signal transduction pathway as
      necessary for proper myosin function. First we show that a lethal P-element
      insertion interacts genetically with zipper. Subsequently we show that this
      second-site noncomplementing mutation disrupts the RhoGEF2 locus. Next, we show
      that two EMS-induced mutations, previously shown to interact genetically with
      zipper(Ebr), disrupt the RhoA locus. Further, we have identified their molecular
      lesions and determined that disruption of the carboxyl-terminal CaaX box gives
      rise to their mutant phenotype. Finally, we show that RhoA mutations themselves
      can be utilized in genetic screens. Biochemical and cell culture analyses suggest
      that Rho signal transduction regulates the activity of myosin. Our studies
      provide direct genetic proof of the biological relevance of regulation of myosin
      by Rho signal transduction in an intact metazoan.

PMID- 10880487
TI  - courtless, the Drosophila UBC7 homolog, is involved in male courtship behavior
      and spermatogenesis.
AB  - The courtless (col) mutation disrupts early steps of courtship behavior in
      Drosophila males, as well as the development of their sperm. Most of the
      homozygous col/col males (78%) do not court at all. Only 5% perform the entire
      ritual and copulate, yet these matings produce no progeny. The col gene maps to
      polytene chromosome band 47D. It encodes two proteins that differ in their
      carboxy termini and are the Drosophila homologs of the yeast ubiquitin
      conjugating enzyme UBC7. The col mutation is caused by an insertion of a P
      element into the 3' UTR of the gene, which probably disrupts translational
      regulatory elements. As a consequence, the homozygous mutants exhibit a six- to
      sevenfold increase in the level of the COL protein. The col product is essential,
      and deletions that remove the col gene are lethal. During embryonic development
      col is expressed primarily in the CNS. Our results implicate the ubiquitin
      mediated system in the development and function of the nervous system and in
      meiosis during spermatogenesis.

PMID- 10880488
TI  - kurtz, a novel nonvisual arrestin, is an essential neural gene in Drosophila.
AB  - The kurtz gene encodes a novel nonvisual arrestin. krz is located at the most
      distal end of the chromosome 3R, the third gene in from the telomere. krz is
      expressed throughout development. During early embryogenesis, krz is expressed
      ubiquitously and later is localized to the central nervous system, maxillary
      cirri, and antennal sensory organs. In late third instar larvae, krz message is
      detected in the fat bodies, the ventral portion of the thoracic-abdominal
      ganglia, the deuterocerebrum, the eye-antennal imaginal disc, and the wing
      imaginal disc. The krz(1) mutation contains a P-element insertion within the only
      intron of this gene and results in a severe reduction of function. Mutations in
      krz have a broad lethal phase extending from late embryogenesis to the third
      larval instar. The fat bodies of krz(1) larva precociously dissociate during the
      midthird instar. krz(1) is a type 1 melanotic tumor gene; the fat body is the
      primary site of melanotic tumor formation during the third instar. We have
      functionally rescued these phenotypes with both genomic and cDNA transgenes.
      Importantly, the expression of a full-length krz cDNA within the CNS rescues the
      krz(1) lethality. These experiments establish the krz nonvisual arrestin as an
      essential neural gene in Drosophila.

PMID- 10880489
TI  - Deletion of an insulator element by the mutation facet-strawberry in Drosophila
      melanogaster.
AB  - Eukaryotic chromosomes are thought to be subdivided into a series of structurally
      and functionally independent units. Critical to this hypothesis is the
      identification of insulator or boundary elements that delimit chromosomal
      domains. The properties of a Notch mutation, facet-strawberry (fa(swb)), suggest
      that this small deletion disrupts such a boundary element. fa(swb) is located in
      the interband separating polytene band 3C7, which contains Notch, from the distal
      band 3C6. The fa(swb) mutation alters the structural organization of the
      chromosome by deleting the interband and fusing 3C7 with 3C6. Genetic studies
      also suggest that fa(swb) compromises the functional autonomy of Notch by
      allowing the locus to become sensitive to chromosomal position effects emanating
      from distal sequences. In the studies reported here, we show that a DNA fragment
      spanning the fa(swb) region can insulate reporter transgenes against chromosomal
      position effects and can block enhancer-promoter interactions. Moreover, we find
      that insulating activity is dependent on sequences deleted in fa(swb). These
      results provide evidence that the element defined by the fa(swb) mutation
      corresponds to an insulator.

PMID- 10880490
TI  - Slipped-strand mispairing at noncontiguous repeats in Poecilia reticulata: a
      model for minisatellite birth.
AB  - The standard slipped-strand mispairing (SSM) model for the formation of variable
      number tandem repeats (VNTRs) proposes that a few tandem repeats, produced by
      chance mutations, provide the "raw material" for VNTR expansion. However, this
      model is unlikely to explain the formation of VNTRs with long motifs (e.g.,
      minisatellites), because the likelihood of a tandem repeat forming by chance
      decreases rapidly as the length of the repeat motif increases. Phylogenetic
      reconstruction of the birth of a mitochondrial (mt) DNA minisatellite in guppies
      suggests that VNTRs with long motifs can form as a consequence of SSM at
      noncontiguous repeats. VNTRs formed in this manner have motifs longer than the
      noncontiguous repeat originally formed by chance and are flanked by one unit of
      the original, noncontiguous repeat. SSM at noncontiguous repeats can therefore
      explain the birth of VNTRs with long motifs and the "imperfect" or "short direct"
      repeats frequently observed adjacent to both mtDNA and nuclear VNTRs.

PMID- 10880491
TI  - Genetic analysis of isometric growth control mechanisms in the zebrafish caudal
      Fin.
AB  - The body and fins of the zebrafish grow rapidly as juveniles and slower as they
      reach maturation. Throughout their lives, the fins grow isometrically with
      respect to the body. Growth of individual fin rays is achieved by the distal
      addition of bony segments. We have investigated the genetic control of mechanisms
      that initiate new segments or control size of newly initiated segments. We find
      that both segment initiation and segment length are regulated during fin growth
      in wild-type fish. We examined the growth properties of lof and sof fin length
      mutants for effects on the number and length of fin ray segments. Fins of lof
      mutants continue to grow rapidly even after wild-type fin growth slows, resulting
      in positive allometric growth and additional fin ray segments. We suggest that
      lof mutants bypass mechanisms that limit segment initiation. Isometric growth is
      retained in sof mutants, resulting in shorter fins one-half the length of wild
      type fins. The primary defect in sof mutants is that fin ray segments are shorter
      than wild-type segments, although segment number is also diminished. Double
      mutants for sof;lof reveal that segment length and segment number are controlled
      in different pathways. Our findings suggest that the lof gene product regulates
      segment initiation and the sof gene product regulates segment length.

PMID- 10880492
TI  - A microsatellite linkage map of rainbow trout (Oncorhynchus mykiss) characterized
      by large sex-specific differences in recombination rates.
AB  - We constructed a genetic linkage map for a tetraploid derivative species, the
      rainbow trout (Oncorhynchus mykiss), using 191 microsatellite, 3 RAPD, 7 ESMP,
      and 7 allozyme markers in three backcross families. The linkage map consists of
      29 linkage groups with potential arm displacements in the female map due to male
      specific pseudolinkage arrangements. Synteny of duplicated microsatellite markers
      was used to identify and confirm some previously reported pseudolinkage
      arrangements based upon allozyme markers. Fifteen centromeric regions (20
      chromosome arms) were identified with a half-tetrad analysis using gynogenetic
      diploids. Female map length is approximately 10 M, but this is a large
      underestimate as many genotyped segments remain unassigned at a LOD threshold of
      3.0. Extreme differences in female:male map distances were observed (ratio F:M,
      3.25:1). Females had much lower recombination rates (0.14:1) in telomeric regions
      than males, while recombination rates were much higher in females within regions
      proximal to the centromere (F:M, 10:1). Quadrivalent formations that appear
      almost exclusively in males are postulated to account for the observed
      differences.

PMID- 10880493
TI  - Cellular consequences in the brain and liver of age-specific selection for rate
      of development in mice.
AB  - Changes in cell number (hyperplasia) and cell size (hypertrophy) in the brain and
      liver are described for mice subjected to 24 generations of age-specific
      restricted index selection for rate of development in body weight. One selection
      treatment (E) altered rate of development between birth and 10 days of age,
      another treatment (L) involved changes in rate of development between 28 and 56
      days of age, while a third control treatment (C) involved random selection. Each
      selection treatment was replicated three times. These age-specific selection
      treatments focused on intervals during ontogeny when different developmental
      processes (hypertrophy or hyperplasia) were more predominant in the control of
      growth. Significant changes in brain and liver weight occurred at both 28 and 70
      days of age. Early selection (E) generated significant changes in the number of
      cells in the brain while later selection (L) had no effect since the brain had
      stopped growth before selection was initiated. For the liver, early and late
      selection produced significant effects on both cell number and cell size. These
      results describe the dynamic and multidimensional aspects of selection in terms
      of its ability to alter different cellular and developmental components of
      complex morphological traits.

PMID- 10880494
TI  - Through a glass, darkly: reflections of mutation from lacI transgenic mice.
AB  - The study of mutational frequency (Mf) and specificity in aging Big Blue lacI
      transgenic mice provides a unique opportunity to determine mutation rates (MR) in
      vivo in different tissues. We found that MR are not static, but rather, vary with
      the age or developmental stage of the tissue. Although Mf increase more rapidly
      early in life, MR are actually lower in younger animals than in older animals.
      For example, we estimate that the changes in Mf are 4.9x10(-8) and 1.1 x 10(-8)
      mutations/base pair/month in the livers of younger mice (<1. 5 months old) and
      older mice (> or =1.5 months old), respectively (a 4-fold decrease), and that the
      MR are 3.9 x 10(-9) and 1.3 x 10(-7) mutations/base pair/cell division,
      respectively ( approximately 30-fold increase). These data also permit an
      estimate of the MR of GC --> AT transitions occurring at 5'-CpG-3' (CpG)
      dinucleotide sequences. Subsequently, the contribution of these transitions to
      age-related demethylation of genomic DNA can be evaluated. Finally, to better
      understand the origin of observed Mf, we consider the contribution of various
      factors, including DNA damage and repair, by constructing a descriptive
      mutational model. We then apply this model to estimate the efficiency of repair
      of deaminated 5-methylcytosine nucleosides occurring at CpG dinucleotide
      sequences, as well as the influence of the Msh2(-/-) DNA repair defect on overall
      DNA repair efficiency in Big Blue mice. We conclude that even slight changes in
      DNA repair efficiency could lead to significant increases in mutation
      frequencies, potentially contributing significantly to human pathogenesis,
      including cancer.

PMID- 10880495
TI  - Combined analyses of data from quantitative trait loci mapping studies.
      Chromosome 4 effects on porcine growth and fatness.
AB  - For many species several similar QTL mapping populations have been produced and
      analyzed independently. Joint analysis of such data could be used to increase
      power to detect QTL and evaluate population differences. In this study, data were
      collated on almost 3000 pigs from seven different F(2) crosses between Western
      commercial breeds and either the European wild boar or the Chinese Meishan breed.
      Genotypes were available for 31 markers on chromosome 4 (on average 8.3 markers
      per population). Data from three traits common to all populations (birth weight,
      mean backfat depth at slaughter or end of test, and growth rate from birth to
      slaughter or end of test) were analyzed for individual populations and jointly. A
      QTL influencing birth weight was detected in one individual population and in the
      combined data, with no significant interaction of the QTL effect with population.
      A QTL affecting backfat that had a significantly greater effect in wild boar than
      in Meishan crosses was detected. Some evidence for a QTL affecting growth rate
      was detected in all populations, with no significant differences between
      populations. This study is the largest F(2) QTL analysis achieved in a livestock
      species and demonstrates the potential of joint analysis.

PMID- 10880496
TI  - The narrow sheath duplicate genes: sectors of dual aneuploidy reveal ancestrally
      conserved gene functions during maize leaf development.
AB  - The narrow sheath mutant of maize displays a leaf and plant stature phenotype
      controlled by the duplicate factor mutations narrow sheath1 and narrow sheath2.
      Mutant leaves fail to develop a lateral domain that includes the leaf margins.
      Genetic data are presented to show that the narrow sheath mutations map to
      duplicated chromosomal regions, reflecting an ancestral duplication of the maize
      genome. Genetic and cytogenetic evidence indicates that the original mutation at
      narrow sheath2 is associated with a chromosomal inversion on the long arm of
      chromosome 4. Meristematic sectors of dual aneuploidy were generated, producing
      plants genetically mosaic for NARROW SHEATH function. These mosaic plants
      exhibited characteristic half-plant phenotypes, in which leaves from one side of
      the plant were of nonmutant morphology and leaves from the opposite side were of
      narrow sheath mutant phenotype. The data suggest that the narrow sheath duplicate
      genes may perform ancestrally conserved, redundant functions in the development
      of a lateral domain in the maize leaf.

PMID- 10880497
TI  - Bayesian mapping of quantitative trait loci for complex binary traits.
AB  - A complex binary trait is a character that has a dichotomous expression but with
      a polygenic genetic background. Mapping quantitative trait loci (QTL) for such
      traits is difficult because of the discrete nature and the reduced variation in
      the phenotypic distribution. Bayesian statistics are proved to be a powerful tool
      for solving complicated genetic problems, such as multiple QTL with nonadditive
      effects, and have been successfully applied to QTL mapping for continuous traits.
      In this study, we show that Bayesian statistics are particularly useful for
      mapping QTL for complex binary traits. We model the binary trait under the
      classical threshold model of quantitative genetics. The Bayesian mapping
      statistics are developed on the basis of the idea of data augmentation. This
      treatment allows an easy way to generate the value of a hypothetical underlying
      variable (called the liability) and a threshold, which in turn allow the use of
      existing Bayesian statistics. The reversible jump Markov chain Monte Carlo
      algorithm is used to simulate the posterior samples of all unknowns, including
      the number of QTL, the locations and effects of identified QTL, genotypes of each
      individual at both the QTL and markers, and eventually the liability of each
      individual. The Bayesian mapping ends with an estimation of the joint posterior
      distribution of the number of QTL and the locations and effects of the identified
      QTL. Utilities of the method are demonstrated using a simulated outbred full-sib
      family. A computer program written in FORTRAN language is freely available on
      request.

PMID- 10880498
TI  - Hitchhiking under positive Darwinian selection.
AB  - Positive selection can be inferred from its effect on linked neutral variation.
      In the restrictive case when there is no recombination, all linked variation is
      removed. If recombination is present but rare, both deterministic and stochastic
      models of positive selection show that linked variation hitchhikes to either low
      or high frequencies. While the frequency distribution of variation can be
      influenced by a number of evolutionary processes, an excess of derived variants
      at high frequency is a unique pattern produced by hitchhiking (derived refers to
      the nonancestral state as determined from an outgroup). We adopt a statistic, H,
      to measure an excess of high compared to intermediate frequency variants. Only a
      few high-frequency variants are needed to detect hitchhiking since not many are
      expected under neutrality. This is of particular utility in regions of low
      recombination where there is not much variation and in regions of normal or high
      recombination, where the hitchhiking effect can be limited to a small (<1 kb)
      region. Application of the H test to published surveys of Drosophila variation
      reveals an excess of high frequency variants that are likely to have been
      influenced by positive selection.

PMID- 10880499
TI  - Joint effects of genetic hitchhiking and background selection on neutral
      variation.
AB  - Due to relatively high rates of strongly selected deleterious mutations,
      directional selection on favorable alleles (causing hitchhiking effects on linked
      neutral polymorphisms) is expected to occur while a deleterious mutation
      selection balance is present in a population. We analyze this interaction of
      directional selection and background selection and study their combined effects
      on neutral variation, using a three-locus model in which each locus is subjected
      to either deleterious, favorable, or neutral mutations. Average heterozygosity is
      measured by simulations (1) at the stationary state under the assumption of
      recurrent hitchhiking events and (2) as a transient level after a single
      hitchhiking event. The simulation results are compared to theoretical
      predictions. It is shown that known analytical solutions describing the
      hitchhiking effect without background selection can be modified such that they
      accurately predict the joint effects of hitchhiking and background on linked,
      neutral variation. Generalization of these results to a more appropriate
      multilocus model (such that background selection can occur at multiple sites)
      suggests that, in regions of very low recombination rates, stationary levels of
      nucleotide diversity are primarily determined by hitchhiking, whereas in regions
      of high recombination, background selection is the dominant force. The
      implications of these results on the identification and estimation of the
      relevant parameters of the model are discussed.

PMID- 10880500
TI  - An integrated framework for the inference of viral population history from
      reconstructed genealogies.
AB  - We describe a unified set of methods for the inference of demographic history
      using genealogies reconstructed from gene sequence data. We introduce the skyline
      plot, a graphical, nonparametric estimate of demographic history. We discuss both
      maximum-likelihood parameter estimation and demographic hypothesis testing.
      Simulations are carried out to investigate the statistical properties of maximum
      likelihood estimates of demographic parameters. The simulations reveal that (i)
      the performance of exponential growth model estimates is determined by a simple
      function of the true parameter values and (ii) under some conditions, estimates
      from reconstructed trees perform as well as estimates from perfect trees. We
      apply our methods to HIV-1 sequence data and find strong evidence that subtypes A
      and B have different demographic histories. We also provide the first (albeit
      tentative) genetic evidence for a recent decrease in the growth rate of subtype
      B.

PMID- 10880501
TI  - Multipoint mapping of viability and segregation distorting loci using molecular
      markers.
AB  - In line-crossing experiments, deviations from Mendelian segregation ratios are
      usually observed for some markers. We hypothesize that these deviations are
      caused by one or more segregation-distorting loci (SDL) linked to the markers. We
      develop both a maximum-likelihood (ML) method and a Bayesian method to map SDL
      using molecular markers. The ML mapping is implemented via an EM algorithm and
      the Bayesian method is performed via the Markov chain Monte Carlo (MCMC). The
      Bayesian mapping is computationally more intensive than the ML mapping but can
      handle more complicated models such as multiple SDL and variable number of SDL.
      Both methods are applied to a set of simulated data and real data from a cross of
      two Scots pine trees.

PMID- 10880502
TI  - Zygotic associations and multilocus statistics in a nonequilibrium diploid
      population.
AB  - The usual approach to characterizing and estimating multilocus associations in a
      diploid population assumes that the population is in Hardy-Weinberg equilibrium.
      The purpose of this study is to develop a set of summary statistics that can be
      used to characterize and estimate the multilocus associations in a nonequilibrium
      population. The concept of "zygotic associations" is first expanded to facilitate
      the development. The summary statistics are calculated using the distribution of
      a random variable, the number of heterozygous loci (K) found in diploid
      individuals in the population. In particular, the variance of K consists of
      single-locus and multilocus components with the latter being the sum of zygotic
      associations between pairs of loci. Simulation results show that the multilocus
      associations in the variance of K are detectable in a sample of moderate size (>
      or =30) when the sum of all pairwise zygotic associations is greater than zero
      and when gene frequency is intermediate. The method presented here is a
      generalization of the well-known development for the Hardy-Weinberg equilibrium
      population and thus may be of more general use in elucidating the multilocus
      organizations in nonequilibrium and equilibrium populations.

PMID- 10880503
TI  - Codominant analysis of banding data from a dominant marker system by normal
      mixtures.
AB  - Amplified fragment length polymorphisms (AFLPs) currently are among the most
      widely used marker systems. In many studies, AFLPs are analyzed on the basis of
      the presence or absence of a band on an electrophoretic gel. As a result,
      dominant homozygous individuals are not distinguished from heterozygous
      individuals, resulting in a considerable loss of information. This article shows
      how codominant information can be obtained if the amount of PCR products is
      quantified. Due to measurement variation, genotyping on the basis of such
      information is not error-free. We propose use of normal mixture distributions to
      determine the most likely genotype, given the data. The method is exemplified
      using AFLP data from sugar beet.

PMID- 10880504
TI  - Maternal-zygotic gene conflict over sex determination: effects of inbreeding.
AB  - There is growing evidence that sex determination in a wide range of organisms is
      determined by interactions between maternal-effect genes and zygotically
      expressing genes. Maternal-effect genes typically produce products (e.g., mRNA or
      proteins) that are placed into the egg during oogenesis and therefore depend upon
      maternal genotype. Here it is shown that maternal-effect and zygotic genes are
      subject to conflicting selective pressures over sex determination in species with
      partial inbreeding or subdivided populations. The optimal sex ratios for maternal
      effect genes and zygotically expressing genes are derived for two models: partial
      inbreeding (sibmating) and subdivided populations with local mating in temporary
      demes (local mate competition). In both cases, maternal-effect genes are selected
      to bias sex determination more toward females than are zygotically expressed
      genes. By investigating the invasion criteria for zygotic genes in a population
      producing the maternal optimum (and vice versa), it is shown that genetic
      conflict occurs between these genes. Even relatively low levels of inbreeding or
      subdivision can result in maternal-zygotic gene conflict over sex determination.
      The generality of maternal-zygotic gene conflict to sex determination evolution
      is discussed; such conflict should be considered in genetic studies of sex
      determining mechanisms.

PMID- 10880505
TI  - Functional interaction between Ku and the werner syndrome protein in DNA end
      processing.
AB  - Werner syndrome (WS) is an autosomal recessive disease characterized by premature
      aging. The gene responsible for the syndrome was recently cloned and shown to
      encode a protein with strong homology to DNA/RNA helicases. In addition, the
      Werner syndrome protein (WRN) possesses an exonuclease activity. Based on the
      homology to helicases it has been proposed that WRN functions in some aspects of
      DNA replication, recombination, or repair. However, there is currently no
      evidence of a role of WRN in any of these processes; therefore, its biological
      function remains unknown. Using a biochemical approach, we have identified two
      polypeptides that bind to the WRN protein. Peptide sequence analysis indicates
      that the two proteins are identical to Ku70 and Ku80, a heterodimer involved in
      double strand DNA break repair by non-homologous DNA end joining. Protein-protein
      interaction studies reveal that WRN binds directly to Ku80 and that this
      interaction is mediated by the amino terminus of WRN. In addition, we show that
      the binding of Ku alters the specificity of the WRN exonuclease. These results
      suggest a potential involvement of WRN in the repair of double strand DNA breaks.

PMID- 10880506
TI  - Mapping the SF2/ASF binding sites in the bovine growth hormone exonic splicing
      enhancer.
AB  - Splicing of the last intron (intron D) of the bovine growth hormone pre-mRNA
      requires the presence of a downstream exonic splicing enhancer (ESE). This
      enhancer is contained within a 115-nucleotide FspI-PvuII (FP) fragment located in
      the middle of the last exon (exon 5). Previous work showed that the splicing
      factor SF2/ASF binds to this FP region and stimulates splicing of intron D in
      vitro. However, the precise sequences recognized by SF2/ASF within the FP region
      had not been determined. Here we used multiple strategies to map the SF2/ASF
      binding sites and determine their importance for ESE function. Taking advantage
      of the fact that SF2/ASF ultraviolet (UV) cross-links specifically to RNA
      containing the FP sequence, we first mapped a major SF2/ASF binding site by UV
      cross-linking and reverse transcription. This strategy identified a 29-nucleotide
      SF2/ASF binding region in the middle of the FP sequence containing the 7
      nucleotide purine-rich motif described previously. Interestingly, this binding
      region is neither sufficient, nor absolutely required for SF2/ASF-mediated
      splicing, suggesting that additional SF2/ASF binding sites are present. The
      location of these additional sites was determined by electrophoretic mobility
      shift analysis of various subfragments of the FP sequence. Antisense 2'-O-methyl
      oligoribonucleotides complementary to selected SF2/ASF binding sites block bovine
      growth hormone intron D splicing. Thus, multiple SF2/ASF binding sites within the
      exonic splicing enhancer contribute to maximal enhancer activity.

PMID- 10880507
TI  - Site-specific conjugation on serine right-arrow cysteine variant monoclonal
      antibodies.
AB  - We have engineered a cysteine residue at position 442 (EU/OU numbering) in the
      third constant domain (C(H)3) of the heavy chain of several IgGs with different
      specificities, isoforms, and variants with the intent to introduce a site for
      chemical conjugation. The variants were expressed in NS0 mouse myeloma cells,
      where monomeric IgG is the major form and formation of aggregate was minimal.
      Monomeric IgG contained no free thiol; however, it was discovered that the
      engineered thiols were reversibly blocked and could be reduced under controlled
      conditions. Following reduction, reactive thiol was conjugated with a cysteine
      specific bifunctional chelator, bromoacetyl-TMT to a humanized 323/A3 IgG4
      variant. Conjugation had no significant effect on antibody affinity. To prove
      that the conjugation was site-specific, an antibody-TMT conjugate was labeled
      with lutetium-177 and subjected to peptide mapping followed by sequence analysis.
      Glu-C digestion demonstrated that 91% of the label was recovered in the COOH
      terminal peptide fragment containing the engineered cysteine.

PMID- 10880508
TI  - A link between blood coagulation and prophenol oxidase activation in arthropod
      host defense.
AB  - Phenol oxidase, a copper-containing enzyme, is widely distributed not only in
      animals but also in plants and fungi, which is responsible for initiating the
      biosynthesis of melanin. Activation of prophenol oxidase in arthropods is
      important in host defense. However, the prophenol oxidase-activating system
      remains poorly understood at the molecular level. Here we show that the
      coagulation cascade of the horseshoe crab Tachypleus tridentatus is linked to
      prophenol oxidase activation, with the oxygen carrier hemocyanin functioning as a
      substitute for prophenol oxidase. Tachypleus clotting enzyme functionally
      transforms hemocyanin to phenol oxidase, and the conversion reaches a plateau at
      1:1 stoichiometry without proteolytic cleavage. The active site-masked clotting
      enzyme also has the same effect, suggesting that complex formation of the
      clotting enzyme with hemocyanin is critical for the conversion. The two systems
      of blood coagulation and prophenol oxidase activation may have evolved from a
      common ancestral protease cascade.

PMID- 10880509
TI  - The orexin OX1 receptor activates a novel Ca2+ influx pathway necessary for
      coupling to phospholipase C.
AB  - Ca(2+) elevations in Chinese hamster ovary cells stably expressing OX(1)
      receptors were measured using fluorescent Ca(2+) indicators fura-2 and fluo-3.
      Stimulation with orexin-A led to pronounced Ca(2+) elevations with an EC(50)
      around 1 nm. When the extracellular [Ca(2+)] was reduced to a submicromolar
      concentration, the EC(50) was increased 100-fold. Similarly, the inositol 1,4,5
      trisphosphate production in the presence of 1 mm external Ca(2+) was about 2
      orders of magnitude more sensitive to orexin-A stimulation than in low
      extracellular Ca(2+). The shift in the potency was not caused by depletion of
      intracellular Ca(2+) but by a requirement of extracellular Ca(2+) for production
      of inositol 1,4,5-trisphosphate. Fura-2 experiments with the "Mn(2+)-quench
      technique" indicated a direct activation of a cation influx pathway by OX(1)
      receptor independent of Ca(2+) release or pool depletion. Furthermore,
      depolarization of the cells to +60 mV, which almost nullifies the driving force
      for Ca(2+) entry, abolished the Ca(2+) response to low concentrations of orexin
      A. The results thus suggest that OX(1) receptor activation leads to two
      responses, (i) a Ca(2+) influx and (ii) a direct stimulation of phospholipase C,
      and that these two responses converge at the level of phospholipase C where the
      former markedly enhances the potency of the latter.

PMID- 10880510
TI  - Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations
      by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein
      coupled receptors.
AB  - Mechano-sensitive and fatty acid-activated K(+) belong to the structural class of
      K(+) channel with two pore domains. Here, we report the isolation and the
      characterization of a novel member of this family. This channel, called TREK2, is
      closely related to TREK1 (78% of homology). Its gene is located on chromosome
      14q31. TREK2 is abundantly expressed in pancreas and kidney and to a lower level
      in brain, testis, colon, and small intestine. In the central nervous system,
      TREK2 has a widespread distribution with the highest levels of expression in
      cerebellum, occipital lobe, putamen, and thalamus. In transfected cells, TREK2
      produces rapidly activating and non-inactivating outward rectifier K(+) currents.
      The single-channel conductance is 100 picosiemens at +40 mV in 150 mm K(+). The
      currents can be strongly stimulated by polyunsaturated fatty acid such as
      arachidonic, docosahexaenoic, and linoleic acids and by lysophosphatidylcholine.
      The channel is also activated by acidification of the intracellular medium. TREK2
      is blocked by application of intracellular cAMP. As with TREK1, TREK2 is
      activated by the volatile general anesthetics chloroform, halothane, and
      isoflurane and by the neuroprotective agent riluzole. TREK2 can be positively or
      negatively regulated by a variety of neurotransmitter receptors. Stimulation of
      the G(s)-coupled receptor 5HT4sR or the G(q)-coupled receptor mGluR1 inhibits
      channel activity, whereas activation of the G(i)-coupled receptor mGluR2
      increases TREK2 currents. These multiple types of regulations suggest that TREK2
      plays an important role as a target of neurotransmitter action.

PMID- 10880511
TI  - Novel subtype of type IIs restriction enzymes. BfiI endonuclease exhibits
      similarities to the EDTA-resistant nuclease Nuc of Salmonella typhimurium.
AB  - The type IIs restriction enzyme BfiI recognizes the non-palindromic nucleotide
      sequence 5'-ACTGGG-3' and cleaves complementary DNA strands 5/4 nucleotides
      downstream of the recognition sequence. The genes coding for the BfiI restriction
      modification (R-M) system were cloned/sequenced and biochemical characterization
      of BfiI restriction enzyme was performed. The BfiI R-M system contained three
      proteins: two N4-methylcytosine methyltransferases and a restriction enzyme.
      Sequencing of bisulfite-treated methylated DNA indicated that each
      methyltransferase modifies cytosines on opposite strands of the recognition
      sequence. The N-terminal part of the BfiI restriction enzyme amino acid sequence
      revealed intriguing similarities to an EDTA-resistant nuclease of Salmonella
      typhimurium. Biochemical analyses demonstrated that BfiI, like the nuclease of S.
      typhimurium, cleaves DNA in the absence of Mg(2+) ions and hydrolyzes an
      artificial substrate bis(p-nitrophenyl) phosphate. However, unlike the
      nonspecific S. typhimurium nuclease, BfiI restriction enzyme cleaves DNA
      specifically. We propose that the DNA-binding specificity of BfiI stems from the
      C-terminal part of the protein. The catalytic N-terminal subdomain of BfiI
      radically differs from that of type II restriction enzymes and is presumably
      similar to the EDTA-resistant nonspecific nuclease of S. typhimurium; therefore,
      BfiI did not require metal ions for catalysis. We suggest that BfiI represents a
      novel subclass of type IIs restriction enzymes that differs from the archetypal
      FokI endonuclease by the fold of its cleavage domain, the domain location, and
      reaction mechanism.

PMID- 10880512
TI  - An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP
      signaling pathways.
AB  - Nod1 is an Apaf-1-like molecule composed of a caspase-recruitment domain (CARD),
      nucleotide-binding domain, and leucine-rich repeats that associates with the CARD
      containing kinase RICK and activates nuclear factor kappaB (NF-kappaB). We show
      that self-association of Nod1 mediates proximity of RICK and the interaction of
      RICK with the gamma subunit of the IkappaB kinase (IKKgamma). Similarly, the RICK
      related kinase RIP associated via its intermediate region with IKKgamma. A mutant
      form of IKKgamma deficient in binding to IKKalpha and IKKbeta inhibited NF-kappaB
      activation induced by RICK or RIP. Enforced oligomerization of RICK or RIP as
      well as of IKKgamma, IKKalpha, or IKKbeta was sufficient for induction of NF
      kappaB activation. Thus, the proximity of RICK, RIP, and IKK complexes may play
      an important role for NF-kappaB activation during Nod1 oligomerization or
      trimerization of the tumor necrosis factor alpha receptor.

PMID- 10880513
TI  - SHP2 mediates the protective effect of interleukin-6 against dexamethasone
      induced apoptosis in multiple myeloma cells.
AB  - Our previous studies have shown that activation of a related adhesion focal
      tyrosine kinase (RAFTK) (also known as Pyk2) is required for dexamethasone (Dex)
      induced apoptosis in multiple myeloma (MM) cells and that human interleukin-6 (IL
      6), a known growth and survival factor for MM cells, blocks both RAFTK activation
      and apoptosis induced by Dex. However, the mechanism whereby IL-6 inhibits Dex
      induced apoptosis is undefined. In this study, we demonstrate that protein
      tyrosine phosphatase SHP2 mediates this protective effect. We show that IL-6
      triggers selective activation of SHP2 and its association with RAFTK in Dex
      treated MM cells. SHP2 interacts with RAFTK through a region other than its Src
      homology 2 domains. We demonstrate that RAFTK is a direct substrate of SHP2 both
      in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK
      mediates its interaction with SHP2. Moreover, overexpression of dominant negative
      SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These
      findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and
      suggest SHP2 as a novel therapeutic target in MM.

PMID- 10880514
TI  - Selective coupling of G protein beta gamma complexes to inhibition of Ca2+
      channels.
AB  - Several mechanisms couple heterotrimeric guanine nucleotide-binding proteins (G
      proteins) to cellular effectors. Although alpha subunits of G proteins (Galpha)
      were the first recognized mediators of receptor-effector coupling, Gbetagamma
      regulation of effectors is now well known. Five Gbeta and 12 Ggamma subunit genes
      have been identified, suggesting through their diversity that specific subunits
      couple selectively to effectors. The molecular determinants of Gbetagamma
      effector coupling, however, are not well understood, and most studies of G
      protein-effector coupling do not support selectivity of Gbetagamma action. To
      explore this issue further, we have introduced recombinant Gbetagamma complexes
      into avian sensory neurons and measured the inhibition of Ca(2+) currents
      mediated by an endogenous phospholipase Cbeta- (PLCbeta) and protein kinase C
      dependent pathway. Activities of Gbetagamma in the native cells were compared
      with enzyme assays performed in vitro. We report a surprising selective
      activation of the PLCbeta pathway by Gbetagamma complexes containing beta(1)
      subunits, whereas beta(2)-containing complexes produced no activation. In
      contrast, when assayed in vitro, PLCbeta and type II adenylyl cyclase did not
      discriminate among these same Gbetagamma complexes, suggesting the possibility
      that additional cellular determinants confer specificity in vivo.

PMID- 10880515
TI  - [D-Arg(1),D-Trp(5,7,9),Leu(11)]Substance P inhibits bombesin-induced mitogenic
      signal transduction mediated by both G(q) and G(12) in Swiss 3T3cells.
AB  - Substance P (SP) analogues including [d-Arg(1),d-Trp(5,7,9), Leu(11)]SP are broad
      spectrum neuropeptide antagonists and potential anticancer agents, but their
      mechanism of action is not fully understood. Here, we examined the mechanism of
      action of [d-Arg(1), d-Trp(5,7,9),Leu(11)]SP as an inhibitor of G protein-coupled
      receptor (GPCR)-mediated signal transduction and cellular DNA synthesis in Swiss
      3T3 cells. Addition of [d-Arg(1),d-Trp(5,7,9), Leu(11)]SP, at 10 micrometer,
      caused a striking rightward shift in the dose-response curves of DNA synthesis
      induced by bombesin, bradykinin, or vasopressin and markedly inhibited the
      activation of p42(mapk) (ERK-2) and p44(mapk) (ERK-1) induced by these GPCR
      agonists. In addition, this SP analogue also prevented the protein kinase C
      dependent activation of protein kinase D induced by these agonists. [d-Arg(1),d
      Trp(5,7,9),Leu(11)]SP, at a concentration (10 micrometer) that inhibited these
      G(q)-mediated events, also prevented GPCR agonist-induced responses mediated
      through the G proteins of the G(12) subfamily. These include bombesin-induced
      assembly of focal adhesions, formation of parallel arrays of actin stress fibers,
      increase in the tyrosine phosphorylation of focal adhesion kinase (FAK),
      p130(Cas), and paxillin, and formation of a complex between FAK and Src. We
      conclude that [d-Arg(1),d-Trp(5,7,9),Leu(11)]SP acts as a mitogenic antagonist of
      neuropeptide GPCRs blocking signal transduction via both G(q) and G(12).

PMID- 10880516
TI  - Hormone interactions to Leu-rich repeats in the gonadotropin receptors. I.
      Analysis of Leu-rich repeats of human luteinizing hormone/chorionic gonadotropin
      receptor and follicle-stimulating hormone receptor.
AB  - The luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor
      (FSHR) have an approximately 350-amino acid-long, N-terminal extracellular
      exodomain. This exodomain binds hormone with high affinity and specificity and
      contains eight to nine putative Leu-rich repeat (LRR) sequences. LRRs are known
      to assume the horseshoe structure in ribonuclease inhibitors, and the inner
      lining of the horseshoe consists of the beta-stranded Leu/Ile-X-Leu/Ile motif. In
      the case of ribonuclease inhibitors, these beta strands interact with
      ribonuclease. However, it is unclear whether the putative LRRs of LHR and FSHR
      play any role in the structure and function. In this work, the beta-stranded
      Leu/Ile residues in all LRRs of the human LHR and FSHR were Ala-scanned and
      characterized. In addition, the 23 residues around LRR2 of LHR were Ala-scanned.
      The results show that beta-stranded Leu and Ile residues in all LRRs are
      important but not equally. These Leu/Ile-X-Leu/Ile motifs appear to form the
      hydrophobic core of the LRR loop, crucial for the LRR structure. Interestingly,
      the hot spots are primarily in the upstream and downstream LRRs of the LHR
      exodomain, whereas important LRRs spread throughout the FSHR exodomain. This may
      explain the distinct hormone specificity despite the structural similarity of the
      two receptors.

PMID- 10880517
TI  - Hormone interactions to Leu-rich repeats in the gonadotropin receptors. III.
      Photoaffinity labeling of human chorionic gonadotropin with receptor Leu-rich
      repeat 4 peptide.
AB  - Human chorionic gonadotropin (hCG) binds to the extracellular N-terminal domain,
      exodomain, of its receptor, and the resulting hCG-exodomain complex is thought to
      modulate the membrane associated domain, endodomain, of the receptor to generate
      hormone signal. The bulk of the exodomain is speculated to assume a crescent
      structure consisting of eight to nine Leu-rich repeats (LRRs), which may provide
      the hormone contact sites. Unfortunately, little experimental evidence is
      available for the precise hormone contact points in the exodomain and the
      endodomain. The two preceding articles (Song, Y., Ji, I., Beauchamp, J., Isaacs,
      N., and Ji, T. (2001) J. Biol. Chem. 276, 3426-3435; Song, Y., Ji, I., Beauchamp,
      J., Isaacs, N., and Ji, T. (2001) J. Biol. Chem. 276, 3436-3442) show that
      putative LRR2 and LRR4 are crucial for hormone binding. In particular, the N
      terminal region of LRR4 assumes the hydrophobic core of the LRR4 loop, whereas
      the C-terminal region is crucial for signal generation. However, it is unclear
      whether LRR4 interacts hCG and the endodomain and how it might be involved in
      signal generation. In this article, our affinity labeling results present the
      first evidence that the N-terminal region of LRR4 interacts with hCG,
      preferentially the hCGalpha subunit and that the hCG/LRR4 complex interacts with
      exoloop 2 of the endodomain. This interaction offers a mechanism to generate
      hormone signal.

PMID- 10880518
TI  - Cotranscriptional cap 4 formation on the Trypanosoma brucei spliced leader RNA.
AB  - mRNA cap formation in trypanosomatid protozoa is mediated through trans-splicing
      of the capped spliced leader (SL) sequence of the SL RNA onto the 5' end of all
      mRNAs. The SL RNA cap structure in Trypanosoma brucei is unique among eukaryotes
      and consists of 7-methylguanosine (m(7)G) followed by four methylated nucleotides
      (cap 4): m(7)Gpppm(2)(6)AmpAmpCmpm(3)Um. Using transcriptional arrest in
      permeable T. brucei cells, we have analyzed the temporal progression of cap 4
      formation on the 140-nucleotide-long SL RNA. m(7)G capping of the SL RNA could be
      detected on prematurely terminated SL RNA transcripts of 56 nucleotides in length
      and longer. Subsequent modifications characteristic of the SL RNA cap 4 were
      added successively in a 5' to 3' direction and appeared to be independent of core
      ribonucleoprotein formation. Transcripts between 56 and 67 nucleotides in length
      were partially modified and carried methyl groups on the first two adenosine
      residues, whereas a fully modified cap 4 structure was present on transcripts
      arrested at position 117 and beyond. Taken together, our results are consistent
      with a cotranscriptional mechanism for generating the cap 4 structure on the SL
      RNA.

PMID- 10880520
TI  - Direct identification of a peptide binding region in the opioid receptor-like 1
      receptor by photoaffinity labeling with [Bpa(10),Tyr(14)]nociceptin.
AB  - The heptadecapeptide nociceptin, also known as orphanin FQ, is the endogenous
      agonist of the opioid receptor-like 1 (ORL1) G protein-coupled receptor. An
      affinity labeling approach has been implemented to probe the interactions of the
      neuropeptide with the receptor using the photolabile nociceptin derivative, [p
      benzoyl-l-Phe(10),Tyr(14)]nociceptin ([Bpa(10),Tyr(14)]noc). In recombinant
      Chinese hamster ovary cells expressing the human ORL1 receptor,
      [Bpa(10),Tyr(14)]noc binds the receptor with high affinity (K(i) approximately
      0.7 nm) and is as potent as nociceptin in the inhibition of forskolin-induced
      cAMP synthesis (EC(50) approximately 0.5 nm). UV irradiation at 365 nm of the
      complex formed by the ORL1 receptor and radioiodinated [Bpa(10),Tyr(14)]noc
      results in the irreversible labeling of a glycoprotein of approximately 65 kDa,
      determined by SDS-polyacrylamide gel electrophoresis. Complete digestion of the
      partially purified 65-kDa complex with kallikrein generates a single labeled
      fragment (approximately 6.5 kDa) that is readily cleaved by endoproteinase Glu-C
      to yield a labeled fragment of approximately 3.2 kDa. Kallikrein treatment of the
      photoaffinity cross-linked Glu(295) --> Asp mutant receptor also yields a single
      labeled fragment of approximately 6.5 kDa but is resistant to further cleavage by
      endoproteinase Glu-C. Based upon the expected proteolytic fingerprint of the
      labeled receptor, the photoreactive region can be identified as ORL1-(296-302;
      residues Thr-Ala-Val-Ala-Ile-Leu-Arg) spanning the C terminus of extracellular
      loop 3 and the N terminus of transmembrane helix VII. Molecular modeling of the
      ORL1 receptor complex with [Bpa(10)]noc suggests that reaction of the Bpa
      carbonyl group may occur with the side chain of Ile(300) within the
      experimentally identified photoreactive region.

PMID- 10880521
TI  - The semiconserved head structure of Plasmodium falciparum erythrocyte membrane
      protein 1 mediates binding to multiple independent host receptors.
AB  - Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate
      but are withdrawn from the peripheral circulation; they are bound to the
      endothelial lining and to uninfected erythrocytes in the microvasculature.
      Blockage of the blood flow, hampered oxygen delivery, and severe malaria may
      follow if binding is excessive. The NH(2)-terminal head structure (Duffy binding
      like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a
      single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here
      shown to mediate adherence to multiple host receptors including platelet
      endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen,
      normal nonimmune immunoglobulin M, three virulence-associated receptor proteins,
      a heparan sulfate-like glucosaminoglycan, and CD36. DBL2delta was found to
      mediate additional binding to PECAM-1/CD31. The exceptional binding activity of
      the PfEMP1 head structure and its relatively conserved nature argues that it
      holds an important role in erythrocyte sequestration and therefore in the
      virulence of the malaria parasite.

PMID- 10880522
TI  - Inhibition of intracellular transport of B cell antigen receptor complexes by
      Kaposi's sarcoma-associated herpesvirus K1.
AB  - The B cell antigen receptor (BCR) is a large complex that consists of a disulfide
      linked tetramer of two transmembrane heavy (mu) chains and two light (lambda or
      kappa) chains in association with a heterodimer of Igalpha and Igbeta. Kaposi's
      sarcoma-associated herpesvirus (KSHV) encodes a transforming protein called K1,
      which has structural and functional similarity to Igalpha and Igbeta. We
      demonstrate that K1 downregulates the expression of BCR complexes on the surface.
      The NH(2)-terminal region of K1 specifically interacts with the mu chains of BCR
      complexes, and this interaction retains BCR complexes in the endoplasmic
      reticulum, preventing their intracellular transport to the cell surface. Thus,
      KSHV K1 resembles Igalpha and Igbeta in its ability to induce signaling and to
      interact with mu chains of the BCR. However, unlike Igalpha and Igbeta, which
      interact with mu chains to direct BCR complexes to the cell surface, K1 interacts
      with mu chains to block the intracellular transport of BCR complexes to the cell
      surface. These results demonstrate a unique feature of the K1 transforming
      protein, which may confer virus-infected cells with a long-term survival
      advantage.

PMID- 10880523
TI  - The toll-like receptor protein RP105 regulates lipopolysaccharide signaling in B
      cells.
AB  - The susceptibility to infections induced by Gram-negative bacteria is largely
      determined by innate immune responses to bacteria cell wall lipopolysaccharide
      (LPS). The stimulation of B cells by LPS enhances their antigen-presenting
      capacity and is accompanied by B cell proliferation and secretion of large
      quantities of LPS-neutralizing antibodies. Similar to macrophages and
      neutrophils, the LPS-induced activation of B cells is dependent on Toll-like
      receptor (TLR)4. Here, we demonstrate that the responses of B cells to LPS are
      also regulated by another TLR protein, RP105, which is predominantly expressed on
      mature B cells in mice and humans. The analysis of mice homozygous for the null
      mutation in the RP105 gene revealed impaired proliferative and humoral immune
      responses of RP105-deficient B cells to LPS. Using originally LPS-unresponsive
      Ba/F3 cells expressing exogenous TLR4 and RP105, we demonstrate the functional
      cooperation between TLR4 and RP105 in LPS-induced nuclear factor kappaB
      activation. These data suggest the existence of the TLR4-RP105 signaling module
      in the LPS-induced B cell activation.

PMID- 10880524
TI  - H2-DMalpha(-/-) mice show the importance of major histocompatibility complex
      bound peptide in cardiac allograft rejection.
AB  - The role played by antigenic peptides bound to major histocompatibility complex
      (MHC) molecules is evaluated with H2-DMalpha(-/)- mice. These mice have
      predominantly class II-associated invariant chain peptide (CLIP)-, not antigenic
      peptide-bound, MHC class II. H2-DMalpha(-/)- donor heart grafts survived three
      times longer than wild-type grafts and slightly longer than I-A(beta)(b)-(/)-
      grafts. Proliferative T cell response was absent, and cytolytic response was
      reduced against the H2-DMalpha(-/)- grafts in vivo. Residual cytolytic T cell and
      antibody responses against intact MHC class I lead to eventual rejection. Removal
      of both H2-DMalpha and beta2-microglobulin (beta2m) in cardiac grafts lead to
      greater (8-10 times) graft survival, whereas removal of beta2m alone did not have
      any effect. These results demonstrate the significance of peptide rather than
      just allogeneic MHC, in eliciting graft rejection.

PMID- 10880525
TI  - Treatment of experimental (Trinitrobenzene sulfonic acid) colitis by intranasal
      administration of transforming growth factor (TGF)-beta1 plasmid: TGF-beta1
      mediated suppression of T helper cell type 1 response occurs by interleukin (IL)
      10 induction and IL-12 receptor beta2 chain downregulation.
AB  - In this study, we show that a single intranasal dose of a plasmid encoding active
      transforming growth factor beta1 (pCMV-TGF-beta1) prevents the development of T
      helper cell type 1 (Th1)-mediated experimental colitis induced by the haptenating
      reagent, 2,4, 6-trinitrobenzene sulfonic acid (TNBS). In addition, such plasmid
      administration abrogates TNBS colitis after it has been established, whereas, in
      contrast, intraperitoneal administration of rTGF-beta1 protein does not have this
      effect. Intranasal pCMV-TGF-beta1 administration leads to the expression of TGF
      beta1 mRNA in the intestinal lamina propria and spleen for 2 wk, as well as the
      appearance of TGF-beta1-producing T cells and macrophages in these tissues, and
      is not associated with the appearances of fibrosis. These cells cause marked
      suppression of interleukin (IL)-12 and interferon (IFN)-gamma production and
      enhancement of IL-10 production; in addition, they inhibit IL-12 receptor beta2
      (IL-12Rbeta2) chain expression. Coadministration of anti-IL-10 at the time of
      pCMV-TGF-beta1 administration prevents the enhancement of IL-10 production and
      reverses the suppression of IL-12 but not IFN-gamma secretion. However, anti-IL
      10 leads to increased tumor necrosis factor alpha production, especially in
      established colitis. Taken together, these studies show that TGF-beta1 inhibition
      of a Th1-mediated colitis is due to: (a) suppression of IL-12 secretion by IL-10
      induction and (b) inhibition of IL-12 signaling via downregulation of IL-12Rbeta2
      chain expression. In addition, TGF-beta1 may also have an inhibitory effect on
      IFN-gamma transcription.

PMID- 10880526
TI  - Inducible costimulator protein (ICOS) controls T helper cell subset polarization
      after virus and parasite infection.
AB  - It has been shown that certain pathogens can trigger efficient T cell responses
      in the absence of CD28, a key costimulatory receptor expressed on resting T
      cells. Inducible costimulator protein (ICOS) is an inducible costimulator
      structurally and functionally related to CD28. Here, we show that in the absence
      of CD28 both T helper cell type 1 (Th1) and Th2 responses were impaired but not
      abrogated after infection with lymphocytic choriomeningitis virus (LCMV),
      vesicular stomatitis virus (VSV), and the nematode Nippostrongylus brasiliensis.
      Inhibition of ICOS in CD28-deficient mice further reduced Th1/Th2 polarization.
      Blocking of ICOS alone had a limited but significant capacity to downregulate Th
      subset development. In contrast, cytotoxic T lymphocyte (CTL) responses, which
      are regulated to a minor and major extent by CD28 after LCMV and VSV infection,
      respectively, remained unaffected by blocking ICOS. Together, our results
      demonstrate that ICOS regulates both CD28-dependent and CD28-independent CD4(+)
      subset (Th1 and Th2) responses but not CTL responses in vivo.

PMID- 10880527
TI  - HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in
      cytolytic function.
AB  - The use of peptide-human histocompatibility leukocyte antigen (HLA) class I
      tetrameric complexes to identify antigen-specific CD8(+) T cells has provided a
      major development in our understanding of their role in controlling viral
      infections. However, questions remain about the exact function of these cells,
      particularly in HIV infection. Virus-specific cytotoxic T lymphocytes exert much
      of their activity by secreting soluble factors such as cytokines and chemokines.
      We describe here a method that combines the use of tetramers and intracellular
      staining to examine the functional heterogeneity of antigen-specific CD8(+) T
      cells ex vivo. After stimulation by specific peptide antigen, secretion of
      interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, macrophage
      inflammatory protein (MIP)-1beta, and perforin is analyzed by FACS((R)) within
      the tetramer-positive population in peripheral blood. Using this method, we have
      assessed the functional phenotype of HIV-specific CD8(+) T cells compared with
      cytomegalovirus (CMV)-specific CD8(+) T cells in HIV chronic infection. We show
      that the majority of circulating CD8(+) T cells specific for CMV and HIV antigens
      are functionally active with regards to the secretion of antiviral cytokines in
      response to antigen, although a subset of tetramer-staining cells was identified
      that secretes IFN-gamma and MIP-1beta but not TNF-alpha. However, a striking
      finding is that HIV-specific CD8(+) T cells express significantly lower levels of
      perforin than CMV-specific CD8(+) T cells. This lack of perforin is linked with
      persistent CD27 expression on HIV-specific cells, suggesting impaired maturation,
      and specific lysis ex vivo is lower for HIV-specific compared with CMV-specific
      cells from the same donor. Thus, HIV-specific CD8(+) T cells are impaired in
      cytolytic activity.

PMID- 10880528
TI  - The GTPase rho controls a p53-dependent survival checkpoint during thymopoiesis.
AB  - During the early stages of thymopoiesis, cell survival is controlled by cytokines
      that regulate the expression of antiapoptotic proteins such as Bcl-2. At the pre
      T cell stage, a critical checkpoint for beta chain selection is monitored by the
      tumor suppressor p53: pre-T cells can survive and differentiate when p53 is
      removed genetically or when its proapoptotic function is inactivated
      physiologically as a consequence of signaling through the pre-T cell receptor
      complex. Previous work has shown that the guanine nucleotide binding protein Rho
      controls cell survival in T cell progenitors. Here we define the survival
      pathways controlled by Rho in pre-T cells and show that this GTPase is a pivotal
      regulator of the p53-mediated checkpoint operating at the time of beta selection:
      loss of Rho function results in apoptosis in pre-T cells, but this cell death is
      prevented by loss of p53. The prevention of cell death by loss of p53 restored
      numbers of early T cell progenitors but did not fully restore thymic cellularity.
      Further analysis revealed that loss of Rho function caused survival defects in
      CD4/8 double-positive thymocytes that is independent of p53 but can be prevented
      by ectopic expression of Bcl-2. These studies highlight that the GTPase Rho is a
      crucial component of survival signaling pathways in at least two different
      thymocyte subpopulations: Rho controls the p53 survival checkpoint in pre-T cells
      and is also crucial for a p53 independent survival signaling pathway in CD4/8
      double positives.

PMID- 10880529
TI  - A B cell superantigen-induced persistent "Hole" in the B-1 repertoire.
AB  - The bacterial toxin protein A from Staphylococcus aureus (SpA) interacts with B
      cell antigen receptors encoded by variable region heavy chain (V(H)) clan III
      genes via a V region framework surface that has been highly conserved during the
      evolution of the adaptive immune system. We have investigated the consequences of
      exposure to this prototypic B cell superantigen, and found that treatment of
      neonates or adults induces a T cell-independent deletion of a large supraclonal
      set of susceptible B cells that includes clan III/V(H) S107 family-expressing
      lymphocytes. In studies of different SpA forms, the magnitude of the induced
      deletion directly correlated with the V(H)-specific binding affinity/avidity.
      Upon cessation of SpA exposure, the representation of conventional splenic (B-2
      subset) lymphocytes normalized; however, we found that the V(H) family-restricted
      deficit of peritoneal B-1 cells persisted. SpA treatment also induced a
      persistent loss of splenic S107-mu transcripts, with a loss of certain natural
      antibodies and specific tolerance to phosphorylcholine immunogens that normally
      recruit protective antimicrobial responses dominated by the S107-expressing B-1
      clone, T15. These studies illustrate how a B cell superantigen can exploit a
      primordial Achilles heel in the immune system, for which B-1 cells, an important
      source of natural antibodies and host immune responses, have special
      susceptibility.

PMID- 10880530
TI  - Negative regulation of T cell proliferation and interleukin 2 production by the
      serine threonine kinase GSK-3.
AB  - Glycogen synthase kinase (GSK)-3 is a protein serine/threonine kinase that
      regulates differentiation and cell fate in a variety of organisms. This study
      examined the role of GSK-3 in antigen-specific T cell responses. Using resting T
      cells from P14 T cell receptor (TCR)-transgenic mice (specific for the
      lymphocytic choriomeningitis virus and H-2D(b)), we demonstrated that GSK-3beta
      was inactivated by serine phosphorylation after viral peptide-specific
      stimulation in vitro. To further investigate the role of GSK-3, we have generated
      a retroviral vector that expresses a constitutively active form of GSK-3beta that
      has an alanine substitution at the regulatory amino acid, serine 9 (GSK-3betaA9).
      Retroviral transduction of P14 TCR-transgenic bone marrow stem cells, followed by
      reconstitution, led to the expression of GSK-3betaA9 in bone marrow chimeric
      mice. T cells from chimeric mice demonstrate a reduction in proliferation and
      interleukin (IL)-2 production. In contrast, in vitro assays done in the presence
      of the GSK-3 inhibitor lithium led to dramatically prolonged T cell proliferation
      and increased IL-2 production. Furthermore, in the presence of lithium, we show
      that nuclear factor of activated T cells (NF-AT)c remains in the nucleus after
      antigen-specific stimulation of T cells. Together, these data demonstrate that
      GSK-3 negatively regulates the duration of T cell responses.

PMID- 10880531
TI  - GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin
      remodeling in committed Th1 cells.
AB  - Committed T helper type 1 (Th1) and Th2 effector cells, resulting from chronic
      antigenic stimulation in interleukin (IL)-12 and IL-4, are implicated in the
      pathology of autoimmune and allergic diseases. Committed Th1 cells cannot be
      induced to change their cytokine profiles in response to antigenic stimulation
      and Th2 cytokine-inducing conditions. Here, we report that ectopic expression of
      GATA-3 induced Th2-specific cytokine expression not only in developing Th1 cells
      but also in otherwise irreversibly committed Th1 cells and a Th1 clone, HDK1.
      Moreover, cAMP, an inhibitor of cytokine production by Th1 cells, markedly
      augmented Th2 cytokine production in GATA-3-expressing Th1 cells. Ectopic
      expression of GATA-3 in developing Th1 cells, but not in Th1 clone HDK1, induced
      endogenous GATA-3, suggesting an autoregulatory mechanism for maintenance of GATA
      3 expression in Th2 cells. Structure-function analyses of GATA-3 revealed that
      the NH(2)-terminal transactivation domain and the COOH-terminal zinc finger
      domain of GATA-3 were critical, whereas the NH(2)-terminal zinc finger domain was
      dispensable for the induction of IL-4. Both zinc fingers, however, were required
      for IL-5 induction. A Th2-specific DNaseI-hypersensitive site of the IL-4 locus
      was detected in GATA-3-expressing Th1 cells. Thus, GATA-3 can change the
      phenotype of committed Th1 cells, previously considered to be irreversible.

PMID- 10880532
TI  - Interferon gamma eliminates responding CD4 T cells during mycobacterial infection
      by inducing apoptosis of activated CD4 T cells.
AB  - In Mycobacterium bovis Bacille Calmette-Guerin (BCG)-infected wild-type mice,
      there was a large expansion of an activated (CD44(hi)) splenic CD4 T cell
      population followed by a rapid contraction of this population to normal numbers.
      Contraction of the activated CD4 T cell population in wild-type mice was
      associated with increased apoptosis of activated CD4 T cells. In BCG-infected
      interferon (IFN)-gamma knockout (KO) mice, the activated CD4 T cell population
      did not undergo apoptosis. These mice accumulated large numbers of CD4(+)CD44(hi)
      T cells that were responsive to mycobacterial antigens. Addition of IFN-gamma to
      cultured splenocytes from BCG-infected IFN-gamma KO mice induced apoptosis of
      activated CD4 T cells. IFN-gamma-mediated apoptosis was abolished by depleting
      adherent cells or Mac-1(+) spleen cells or by inhibiting nitric oxide synthase.
      Thus, IFN-gamma is essential to a regulatory mechanism that eliminates activated
      CD4 T cells and maintains CD4 T cell homeostasis during an immune response.

PMID- 10880533
TI  - Failure to suppress the expansion of the activated CD4 T cell population in
      interferon gamma-deficient mice leads to exacerbation of experimental autoimmune
      encephalomyelitis.
AB  - Mice deficient in interferon (IFN)-gamma or IFN-gamma receptor develop
      progressive and fatal experimental autoimmune encephalomyelitis (EAE). We
      demonstrate that CD4 T cells lacking IFN-gamma production were required to
      passively transfer EAE, indicating that they were disease-mediating cells in IFN
      gamma knockout (KO) mice. IFN-gamma KO mice accumulated 10-16-fold more activated
      CD4 T cells (CD4(+)CD44(hi)) than wild-type mice in the central nervous system
      during EAE. CD4(+)CD44(hi) T cells in the spleen and central nervous system of
      IFN-gamma KO mice during EAE showed markedly increased in vivo proliferation and
      significantly decreased ex vivo apoptosis compared with those of wild-type mice.
      IFN-gamma KO CD4(+)CD44(hi) T cells proliferated extensively to antigen
      restimulation in vitro and accumulated larger numbers of live CD4(+) CD44(hi) T
      cells. IFN-gamma completely suppressed proliferation and significantly induced
      apoptosis of CD4(+)CD44(hi) T cells responding to antigen and hence inhibited
      accumulation of live, activated CD4 T cells. We thus present novel in vivo and in
      vitro evidence that IFN-gamma may limit the extent of EAE by suppressing
      expansion of activated CD4 T cells.

PMID- 10880534
TI  - BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation
      antigen and is important for maintaining the peripheral B cell population.
AB  - The tumor necrosis factor (TNF) family member B cell activating factor (BAFF)
      binds B cells and enhances B cell receptor-triggered proliferation. We find that
      B cell maturation antigen (BCMA), a predicted member of the TNF receptor family
      expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was
      previously localized to the Golgi apparatus, BCMA was found to be expressed on
      the surface of transfected cells and tonsillar B cells. A soluble form of BCMA,
      which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease
      in the number of peripheral B cells when administered in vivo. Moreover,
      culturing splenic cells in the presence of BAFF increased survival of a
      percentage of the B cells. These results are consistent with a role for BAFF in
      maintaining homeostasis of the B cell population.

PMID- 10880535
TI  - TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family
      member involved in B cell regulation.
AB  - We and others recently reported tumor necrosis factor (TNF) and apoptosis ligand
      related leukocyte-expressed ligand 1 (TALL-1) as a novel member of the TNF ligand
      family that is functionally involved in B cell proliferation. Transgenic mice
      overexpressing TALL-1 have severe B cell hyperplasia and lupus-like autoimmune
      disease. Here, we describe expression cloning of a cell surface receptor for TALL
      1 from a human Burkitt's lymphoma RAJI cell library. The cloned receptor is
      identical to the previously reported TNF receptor (TNFR) homologue transmembrane
      activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI).
      Murine TACI was subsequently isolated from the mouse B lymphoma A20 cells. Human
      and murine TACI share 54% identity overall. Human TACI exhibits high binding
      affinities to both human and murine TALL-1. Soluble TACI extracellular domain
      protein specifically blocks TALL-1-mediated B cell proliferation without
      affecting CD40- or lipopolysaccharide-mediated B cell proliferation in vitro. In
      addition, when injected into mice, soluble TACI inhibits antibody production to
      both T cell-dependent and -independent antigens. By yeast two-hybrid screening of
      a B cell library with TACI intracellular domain, we identified that, like many
      other TNFR family members, TACI intracellular domain interacts with TNFR
      associated factor (TRAF)2, 5, and 6. Correspondingly, TACI activation in a B cell
      line results in nuclear factor kappaB and c-Jun NH(2)-terminal kinase activation.
      The identification and characterization of the receptor for TALL-1 provides
      useful information for the development of a treatment for B cell-mediated
      autoimmune diseases such as systemic lupus erythematosus.

PMID- 10880536
TI  - Immature dendritic cells acquire CD8(+) cytotoxic T lymphocyte priming capacity
      upon activation by T helper cell-independent or -dependent stimuli.
AB  - The well defined, immature murine dendritic cell (DC) line D1 was used to study
      the role of DC maturation in CTL induction in vitro and in vivo. Maturation of D1
      cells, characterized by markedly increased expression of MHC and costimulatory
      molecules, was induced by incubation with lipopolysaccharide, agonistic CD40
      antibody, or specific CD4(+) T helper (Th) cells. Activated, but not immature, D1
      cells efficiently primed alloreactive T cell responses in vitro. Similarly,
      priming of CTL immunity in vivo in CD4-depleted mice was only observed if these
      mice were immunized with activated D1 cells. This study provides formal evidence
      that activation of DCs, induced by Th-independent as well as Th-dependent
      stimuli, is essential for efficient induction of CTL responses.

PMID- 10880537
TI  - Estrogen deficiency: In search of symptom control and sexuality.

PMID- 10880538
TI  - Promiscuous transcription of vascular endothelial growth factor and survival of
      tumors.

PMID- 10880539
TI  - Medicare to cover routine care costs in clinical trials.

PMID- 10880540
TI  - Antioxidants and cancer: what is the evidence?

PMID- 10880541
TI  - Despite embargo, biotechnology in Cuba thrives.

PMID- 10880542
TI  - Stat bite: All-cancer mortality in Cuba, 1964-1996.

PMID- 10880543
TI  - Latin American school welcomes international students.

PMID- 10880544
TI  - Cuban vaccine tested in Canadian trial.

PMID- 10880545
TI  - Green tea experiments in lab, clinic yield mixed results.

PMID- 10880546
TI  - Molecular markers may improve colon cancer staging, screening.

PMID- 10880547
TI  - Mitochondrion as a novel target of anticancer chemotherapy.
AB  - Mitochondrial membrane permeabilization is a critical event in the process
      leading to physiologic or chemotherapy-induced apoptosis (programmed cell death).
      This permeabilization event is, at least in part, under the control of the
      permeability transition pore complex (PTPC). Oncoproteins from the Bcl-2 family
      and tumor suppressor proteins from the Bax family interact with PTPC to inhibit
      or facilitate membrane permeabilization, respectively. Conventional
      chemotherapeutic agents elicit mitochondrial permeabilization in an indirect
      fashion by induction of endogenous effectors that are involved in the physiologic
      control of apoptosis. However, an increasing number of experimental anticancer
      drugs, including lonidamine, arsenite, betulinic acid, CD437, and several
      amphipathic cationic alpha-helical peptides, act directly on mitochondrial
      membranes and/or on the PTPC. Such agents may induce apoptosis in circumstances
      in which conventional drugs fail to act because endogenous apoptosis induction
      pathways, such as those involving p53, death receptors, or apical caspase
      activation, are disrupted. However, stabilization of the mitochondrial membrane
      by antiapoptotic Bcl-2-like proteins reduces the cytotoxic potential of most of
      these drugs. Targeting of specific PTPC components may overcome this Bcl-2
      mediated apoptosis inhibition. One strategy involves cross-linking of critical
      redox-sensitive thiol groups within the PTPC; another involves the use of ligands
      to the mitochondrial benzodiazepine receptor. Thus, the design of mitochondrion
      targeted cytotoxic drugs may constitute a novel strategy for overcoming apoptosis
      resistance.

PMID- 10880548
TI  - Managing menopausal symptoms in breast cancer survivors: results of a randomized
      controlled trial.
AB  - BACKGROUND: Menopausal symptoms (e.g., hot flashes, vaginal dryness, and stress
      urinary incontinence) are very common in breast cancer survivors and cannot be
      managed with standard estrogen replacement therapy (ERT) in these patients. The
      purpose of this study was to test the efficacy of a comprehensive menopausal
      assessment (CMA) intervention program in achieving relief of symptoms, the
      improvement in quality of life (QOL), and sexual functioning in breast cancer
      survivors. METHODS: Using a two-group, randomized controlled design, we assigned
      76 postmenopausal breast cancer survivors with at least one severe target symptom
      either to the intervention group or to a usual-care group. Seventy-two women were
      evaluable at the end of the study period. The CMA intervention, delivered by a
      nurse practitioner, focused on symptom assessment, education, counseling and, as
      appropriate, specific pharmacologic and behavioral interventions for each of the
      three target symptoms. Psychosocial symptoms were assessed with the use of a self
      report screening instrument, and distressed women were referred for counseling if
      needed. The intervention took place over a 4-month period. Outcomes measured were
      scores on a composite menopausal symptom scale, the RAND Short Form Health Survey
      Vitality Scale, and the Cancer Rehabilitation Evaluation System (CARES) Sexual
      Functioning Scale at baseline and at 4-month follow-up. All statistical tests
      were two-sided and were performed at the alpha =. 05 significance level. RESULTS:
      Patients receiving the intervention demonstrated statistically significant
      improvement (P =.0004) in menopausal symptoms but no significant change in
      vitality (P =.77). Sexual functioning was statistically significantly improved (P
      =.04) in the treatment group compared with the usual-care group. CONCLUSIONS: A
      clinical assessment and intervention program for menopausal symptom management in
      breast cancer survivors is feasible and acceptable to patients, leading to
      reduction in symptoms and improvement in sexual functioning. Measurable
      improvement in a general QOL measure was not demonstrated.

PMID- 10880549
TI  - Focal adhesion kinase, Rap1, and transcriptional induction of vascular
      endothelial growth factor.
AB  - BACKGROUND: Signals from a cell's environment are sensed by receptors, which
      activate pathways that, in turn, transmit the signals to the nucleus, informing
      decisions on growth, angiogenesis, and other cell functions. Transcription of
      vascular endothelial growth factor (VEGF), a potent angiogenic factor, can be
      induced by cell-cell contact. In the current work, we sought to determine if this
      induction is dependent on transformation of cells to a malignant phenotype and
      subsequently to determine which signaling molecules mediate activation of VEGF
      transcription. METHODS: Normal and transformed prostate epithelial cell lines
      were examined at various cell densities to simulate the effect of increased cell
      contact on expression of VEGF messenger RNA. Transformed cells were also
      cotransfected with a VEGF promoter-reporter construct and with constructs that
      express dominant negative or activated versions of signal transduction proteins
      hypothesized to be involved in the cell-cell contact process, and reporter
      activity was assessed at various cell densities. All P values are two-sided.
      RESULTS: Direct cell-cell contact, but not extracellular matrix components,
      resulted in transcriptional activation of a VEGF promoter-reporter construct in
      malignant (P<.0001) but not in nonmalignant (P =.37) prostate cells. This process
      was mediated via a mitogen-activated protein kinase (MAPK); it required the
      activity of focal adhesion kinase (FAK), Rap1, and Raf and was Ras independent.
      In addition, transcriptional activation of a Ras-sensitive Elk-1 chimeric
      reporter by cell-cell contact suggests that Rap1 is a key factor in regulating
      the specificity of convergent MAPK-signaling pathways arising from different
      upstream extracellular stimuli. CONCLUSIONS: Cell contact induction of VEGF
      transcription via FAK and Rap1 provides a novel Ras-independent, but
      transformation-dependent, mechanism for stimulus-specific regulation of tumor
      VEGF expression via MAPK.

PMID- 10880550
TI  - Randomized trial of paclitaxel plus supportive care versus supportive care for
      patients with advanced non-small-cell lung cancer.
AB  - BACKGROUND: In phase II trials, paclitaxel has been shown to have antitumor
      activity in patients with advanced non-small-cell lung cancer (NSCLC). However,
      the survival and quality-of-life (QOL) benefits of paclitaxel used as a single
      agent compared with supportive care alone have not been assessed in a randomized
      clinical trial. METHODS: A total of 157 patients with stage IIIB or IV NSCLC who
      had received no prior chemotherapy were randomly assigned to receive either best
      supportive care alone (78 patients) or paclitaxel plus supportive care (79
      patients). Paclitaxel was administered as a 3-hour intravenous infusion every 3
      weeks. Supportive care included palliative radiotherapy and supportive therapy
      with corticosteroids, antibiotics, analgesics, antiemetics, transfusions, and
      other symptomatic therapy as required. The primary end point of the study was
      survival. Time to disease progression, response rate, adverse events, and QOL
      were secondary end points. RESULTS: Pretreatment characteristics were evenly
      distributed between the two arms. Survival was statistically significantly better
      in the paclitaxel plus supportive care arm than in the supportive care alone arm
      (two-sided P =.037) (median survival = 6.8 months versus 4.8 months). Cox
      multivariate analysis showed paclitaxel plus supportive care to be statistically
      significantly associated with improved survival (two-sided P =.048). QOL was
      similar for both treatment arms, except for the functional activity score of the
      Rotterdam Symptom Checklist, where QOL data statistically significantly favored
      the paclitaxel plus supportive care arm (two-sided P =.043). CONCLUSION: The
      addition of paclitaxel to best supportive care significantly improved survival
      and time to disease progression compared with best supportive care in patients
      with advanced NSCLC and may improve some aspects of QOL.

PMID- 10880551
TI  - Breast density as a predictor of mammographic detection: comparison of interval-
      and screen-detected cancers.
AB  - BACKGROUND: Screening mammography is the best method to reduce mortality from
      breast cancer, yet some breast cancers cannot be detected by mammography. Cancers
      diagnosed after a negative mammogram are known as interval cancers. This study
      investigated whether mammographic breast density is related to the risk of
      interval cancer. METHODS: Subjects were selected from women participating in
      mammographic screening from 1988 through 1993 in a large health maintenance
      organization based in Seattle, WA. Women were eligible for the study if they had
      been diagnosed with a first primary invasive breast cancer within 24 months of a
      screening mammogram and before a subsequent one. Interval cancer case subjects (n
      = 149) were women whose breast cancer occurred after a negative or benign
      mammographic assessment. Screen-detected control subjects (n = 388) were
      diagnosed after a positive screening mammogram. One radiologist, who was blinded
      to cancer status, assessed breast density by use of the American College of
      Radiology Breast Imaging Reporting and Data System. RESULTS: Mammographic
      sensitivity (i.e., the ability of mammography to detect a cancer) was 80% among
      women with predominantly fatty breasts but just 30% in women with extremely dense
      breasts. The odds ratio (OR) for interval cancer among women with extremely dense
      breasts was 6.14 (95% confidence interval [CI] = 1.95-19.4), compared with women
      with extremely fatty breasts, after adjustment for age at index mammogram,
      menopausal status, use of hormone replacement therapy, and body mass index. When
      only those interval cancer cases confirmed by retrospective review of index
      mammograms were considered, the OR increased to 9.47 (95% CI = 2.78-32.3).
      CONCLUSION: Mammographic breast density appears to be a major risk factor for
      interval cancer.

PMID- 10880552
TI  - Ovarian carcinoma in situ with germline BRCA1 mutation and loss of heterozygosity
      at BRCA1 and TP53.
AB  - BACKGROUND: The two-hit hypothesis for the genesis of cancer predicts that cancer
      can develop when the wild-type allele of a tumor suppressor gene is lost in an
      individual with a germline mutation in that gene. Neither loss of heterozygosity
      (LOH) for BRCA1 nor mutations of the TP53 (also known as p53) gene have been
      documented prior to invasion in ovarian cancers arising in women with germline
      BRCA1 mutations. Such documentation is difficult because lesions are rarely
      identified in ovarian epithelium. We, therefore, looked for LOH at microsatellite
      polymorphisms linked to the BRCA1 and TP53 tumor suppressor loci in an incidental
      carcinoma in situ of the ovary removed prophylactically from a woman with a
      germline BRCA1 mutation. METHODS: By use of laser-capture microdissection, we
      obtained pure populations of atypical ovarian epithelial cells and normal stromal
      cells. DNA was extracted, amplified with primers flanking polymorphic
      microsatellites linked to BRCA1 (D17S855 and D17S579) and TP53 (TP53 and
      D17S786), and analyzed for LOH at these microsatellites. We also tested for p53
      expression in the abnormal epithelium by immunohistochemistry. RESULTS: Both of
      the markers linked to TP53 showed LOH, as did an intragenic BRCA1-linked marker
      (D17S855). The other microsatellite marker for BRCA1 was uninformative.
      Immunohistochemical staining with an antibody to p53 showed strong
      immunoreactivity confined to the atypical epithelium. CONCLUSIONS: BRCA1, as well
      as TP53, can undergo LOH prior to stromal invasion in BRCA1-associated ovarian
      cancer. Strong immunoreactivity for p53 suggests the presence of mutated p53 in
      these cells as well. These findings suggest that loss of function of these two
      tumor suppressor genes occurs early in ovarian carcinogenesis in BRCA1 mutation
      carriers.

PMID- 10880553
TI  - Breast cancer screening using small-angle X-ray scattering analysis of human
      hair.

PMID- 10880554
TI  - Body size and testicular cancer.

PMID- 10880555
TI  - Role of diabetes mellitus in the etiology of hepatocellular carcinoma.

PMID- 10880556
TI  - Re: Effect of hormone replacement therapy on breast cancer risk: estrogen versus
      estrogen plus progestin.

PMID- 10880557
TI  - RESPONSE: re: effect of hormone replacement therapy on breast cancer risk:
      estrogen versus estrogen plus progestin

PMID- 10880558
TI  - Re: Dormancy of mammary carcinoma after mastectomy.

PMID- 10880559
TI  - RESPONSE: re: dormancy of mammary carcinoma after mastectomy

PMID- 10880561
TI  - Memory landscapes of single-enzyme molecules.
AB  - Immobilized single horseradish peroxidase enzymes were observed by confocal
      fluorescence spectroscopy during catalysis of the oxidation reaction of the
      nonfluorescent dihydrorhodamine 6G substrate into the highly fluorescent product
      rhodamine 6G. By extracting only the non-Markovian behavior of the spectroscopic
      two-state process of enzyme-product complex formation and release, memory
      landscapes were generated for single-enzyme molecules. The memory landscapes can
      be used to discriminate between different origins of stretched exponential
      kinetics that are found in the first-order correlation analysis. Memory
      landscapes of single-enzyme data shows oscillations that are expected in a single
      enzyme system that possesses a set of transient states. Alternative origins of
      the oscillations may not, however, be ruled out. The data and analysis indicate
      that substrate interaction with the enzyme selects a set of conformational
      substates for which the enzyme is active.

PMID- 10880560
TI  - Crystal structure of an anti-carbohydrate antibody directed against Vibrio
      cholerae O1 in complex with antigen: molecular basis for serotype specificity.
AB  - The crystal structure of the murine Fab S-20-4 from a protective anti-cholera Ab
      specific for the lipopolysaccharide Ag of the Ogawa serotype has been determined
      in its unliganded form and in complex with synthetic fragments of the Ogawa O
      specific polysaccharide (O-SP). The upstream terminal O-SP monosaccharide is
      shown to be the primary antigenic determinant. Additional perosamine residues
      protrude outwards from the Ab surface and contribute only marginally to the
      binding affinity and specificity. A complementary water-excluding hydrophobic
      interface and five Ab-Ag hydrogen bonds are crucial for carbohydrate recognition.
      The structure reported here explains the serotype specificity of anti-Ogawa Abs
      and provides a rational basis toward the development of a synthetic carbohydrate
      based anti-cholera vaccine.

PMID- 10880562
TI  - Microtubule self-organization is gravity-dependent.
AB  - Although weightlessness is known to affect living cells, the manner by which this
      occurs is unknown. Some reaction-diffusion processes have been theoretically
      predicted as being gravity-dependent. Microtubules, a major constituent of the
      cellular cytoskeleton, self-organize in vitro by way of reaction-diffusion
      processes. To investigate how self-organization depends on gravity, microtubules
      were assembled under low gravity conditions produced during space flight.
      Contrary to the samples formed on an in-flight 1 x g centrifuge, the samples
      prepared in microgravity showed almost no self-organization and were locally
      disordered.

PMID- 10880563
TI  - The transcription factor EPAS-1/hypoxia-inducible factor 2alpha plays an
      important role in vascular remodeling.
AB  - We have studied the role of the basic helix-loop-helix-PAS transcription factor
      EPAS-1/hypoxia-inducible factor 2alpha in vascular development by gene targeting.
      In ICR/129 Sv outbred background, more than half of the mutants displayed varying
      degrees of vascular disorganization, typically in the yolk sac, and died in utero
      between embryonic day (E)9.5 and E13.5. In mutant embryos directly derived from
      EPAS-1(-/-) embryonic stem cells (hence in 129 Sv background), all embryos
      developed severe vascular defects both in the yolk sac and embryo proper and died
      between E9.5 and E12.5. Normal blood vessels were formed by vasculogenesis but
      they either fused improperly or failed to assemble into larger vessels later
      during development. Our results suggest that EPAS-1 plays an important role at
      postvasculogenesis stages and is required for the remodeling of the primary
      vascular network into a mature hierarchy pattern.

PMID- 10880564
TI  - CTXphi contains a hybrid genome derived from tandemly integrated elements.
AB  - CTXphi is a filamentous, temperate bacteriophage whose genome includes ctxAB, the
      genes that encode cholera toxin. In toxigenic isolates of Vibrio cholerae, tandem
      arrays of prophage DNA, usually interspersed with the related genetic element
      RS1, are integrated site-specifically within the chromosome. We have discovered
      that these arrays routinely yield hybrid virions, composed of DNA from two
      adjacent prophages or from a prophage and a downstream RS1. Coding sequences are
      always derived from the 5' prophage whereas most of an intergenic sequence,
      intergenic region 1, is always derived from the 3' element. The presence of
      tandem elements is required for production of virions: V. cholerae strains that
      contain a solitary prophage rarely yield CTX virions, and the few virions
      detected result from imprecise excision of prophage DNA. Thus, generation of the
      replicative form of CTXphi, pCTX, a step that precedes production of virions,
      does not depend on reversal of the process for site-specific integration of
      CTXphi DNA into the V. cholerae chromosome. Production of pCTX also does not
      depend on RecA-mediated homologous recombination between adjacent prophages. We
      hypothesize that the CTXphi-specific proteins required for replication of pCTX
      can also function on a chromosomal substrate, and that, unlike the processes used
      by other integrating phages, production of pCTX and CTXphi does not require
      excision of the prophage from the chromosome. Use of this replication strategy
      maximizes vertical transmission of prophage DNA while still enabling
      dissemination of CTXphi to new hosts.

PMID- 10880565
TI  - Activation of polyamine catabolism in transgenic rats induces acute pancreatitis.
AB  - Polyamines are required for optimal growth and function of cells. Regulation of
      their cellular homeostasis is therefore tightly controlled. The key regulatory
      enzyme for polyamine catabolism is the spermidine/spermine N(1)-acetyltransferase
      (SSAT). Depletion of cellular polyamines has been associated with inhibition of
      growth and programmed cell death. To investigate the physiological function SSAT,
      we generated a transgenic rat line overexpressing the SSAT gene under the control
      of the inducible mouse metallothionein I promoter. Administration of zinc
      resulted in a marked induction of pancreatic SSAT, overaccumulation of
      putrescine, and appearance of N(1)-acetylspermidine with extensive depletion of
      spermidine and spermine in transgenic animals. The activation of pancreatic
      polyamine catabolism resulted in acute pancreatitis. In nontransgenic animals, an
      equal dose of zinc did not affect pancreatic polyamine pools, nor did it induce
      pancreatitis. Acetylated polyamines, products of the SSAT-catalyzed reaction, are
      metabolized further by the polyamine oxidase (PAO) generating hydrogen peroxide,
      which might cause or contribute to the pancreatic inflammatory process.
      Administration of specific PAO inhibitor, MDL72527 [N(1),N(2)-bis(2,3-butadienyl)
      1,4-butanediamine], however, did not affect the histological score of the
      pancreatitis. Induction of SSAT by the polyamine analogue N(1),N(11)
      diethylnorspermine reduced pancreatic polyamines levels only moderately and
      without signs of organ inflammation. In contrast, the combination of N(1), N(11)
      diethylnorspermine with MDL72527 dramatically activated SSAT, causing profound
      depletion of pancreatic polyamines and acute pancreatitis. These results
      demonstrate that acute induction of SSAT leads to pancreatic inflammation,
      suggesting that sufficient pools of higher polyamine levels are essential to
      maintain pancreatic integrity. This inflammatory process is independent of the
      production of hydrogen peroxide by PAO.

PMID- 10880566
TI  - Site-specific conformational determination in thermal unfolding studies of
      helical peptides using vibrational circular dichroism with isotopic substitution.
AB  - Understanding the detailed mechanism of protein folding requires dynamic, site
      specific stereochemical information. The short time response of vibrational
      spectroscopies allows evaluation of the distribution of populations in rapid
      equilibrium as the peptide unfolds. Spectral shifts associated with isotopic
      labels along with local stereochemical sensitivity of vibrational circular
      dichroism (VCD) allow determination of the segment sequence of unfolding. For a
      series of alanine-rich peptides that form alpha-helices in aqueous solution, we
      used isotopic labeling and VCD to demonstrate that the alpha-helix
      noncooperatively unwinds from the ends with increasing temperature. For these
      blocked peptides, the C-terminal is frayed at 5 degrees C. Ab initio level
      theoretical simulations of the IR and VCD band shapes are used to analyze the
      spectra and to confirm the conformation of the labeled components. The VCD
      signals associated with the labeled residues are amplified by coupling to the
      nonlabeled parts of the molecule. Thus small labeled segments are detectable and
      stereochemically defined in moderately large peptides in this report of site
      specific peptide VCD conformational analysis.

PMID- 10880567
TI  - Biosynthesis of terpenoids: 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase
      from tomato.
AB  - The putative catalytic domain (residues 81-401) of a predicted tomato protein
      with similarity to 4-diphosphocytidyl-2-C-methyl-d-erythritol kinase of
      Escherichia coli was expressed in a recombinant E. coli strain. The protein was
      purified to homogeneity and was shown to catalyze the phosphorylation of the
      position 2 hydroxy group of 4-diphosphocytidyl-2-C-methyl-d-erythritol at a rate
      of 33 micromol small middle dotmg(-1) small middle dotmin(-1). The structure of
      the reaction product, 4-diphosphocytidyl-2-C-methyl-d-erythritol 2-phosphate, was
      established by NMR spectroscopy. Divalent metal ions, preferably Mg(2+), are
      required for activity. Neither the tomato enzyme nor the E. coli ortholog
      catalyzes the phosphorylation of isopentenyl monophosphate.

PMID- 10880568
TI  - A cytotoxic ribonuclease which specifically cleaves four isoaccepting arginine
      tRNAs at their anticodon loops.
AB  - Colicin D has long been thought to stop protein synthesis in infected Escherichia
      coli cells by inactivating ribosomes, just like colicin E3. Here, we show that
      colicin D specifically cleaves tRNAs(Arg) including four isoaccepting molecules
      both in vivo and in vitro. The cleavage occurs in vitro between positions 38 and
      39 in an anticodon loop with a 2',3'-cyclic phosphate end, and is inhibited by a
      specific immunity protein. Consistent with the cleavage of tRNAs(Arg), the RNA
      fraction of colicin-treated cells significantly reduced the amino acid-accepting
      activity only for arginine. Furthermore, we generated a single mutation of
      histidine in the C-terminal possible catalytic domain, which caused the loss of
      the killing activity in vivo together with the tRNA(Arg)-cleaving activity both
      in vivo and in vitro. These findings show that colicin D directly cleaves
      cytoplasmic tRNAs(Arg), which leads to impairment of protein synthesis and cell
      death. Recently, we found that colicin E5 stops protein synthesis by cleaving the
      anticodons of specific tRNAs for Tyr, His, Asn, and Asp. Despite these apparently
      similar actions on tRNAs and cells, colicins D and E5 not only exhibit no
      sequence homology but also have different molecular mechanisms as to both
      substrate recognition and catalytic reaction.

PMID- 10880569
TI  - Regulation of CFTR Cl- channel gating by ATP binding and hydrolysis.
AB  - Opening and closing of the cystic fibrosis transmembrane conductance regulator
      (CFTR) Cl(-) channel is regulated by the interaction of ATP with its two
      cytoplasmic nucleotide-binding domains (NBD). Although ATP hydrolysis by the NBDs
      is required for normal gating, the influence of ATP binding versus hydrolysis on
      specific steps in the gating cycle remains uncertain. Earlier work showed that
      the absence of Mg(2+) prevents hydrolysis. We found that even in the absence of
      Mg(2+), ATP could support channel activity, albeit at a reduced level compared
      with the presence of Mg(2+). Application of ATP with a divalent cation, including
      the poorly hydrolyzed CaATP complex, increased the rate of opening. Moreover, in
      CFTR variants with mutations that disrupt hydrolysis, ATP alone opened the
      channel and Mg(2+) further enhanced ATP-dependent opening. These data suggest
      that ATP alone can open the channel and that divalent cations increase ATP
      binding. Consistent with this conclusion, when we mutated an aspartate thought to
      bind Mg(2+), divalent cations failed to increase activity compared with ATP
      alone. Two observations suggested that divalent cations also stabilize the open
      state. In wild-type CFTR, CaATP generated a long duration open state, whereas ATP
      alone did not. With a CFTR variant in which hydrolysis was disrupted, MgATP, but
      not ATP alone, produced long openings. These results suggest a gating cycle for
      CFTR in which ATP binding opens the channel and either hydrolysis or dissociation
      leads to channel closure. In addition, the data suggest that ATP binding and
      hydrolysis by either NBD can gate the channel.

PMID- 10880570
TI  - The central cytoplasmic loop of the major facilitator superfamily of transport
      proteins governs efficient membrane insertion.
AB  - Deletion of 5 residues (Delta5) from the central cytoplasmic loop of the lactose
      permease of Escherichia coli has no significant effect on expression or activity,
      whereas Delta12 leads to increased rates of permease turnover after membrane
      insertion and decreased transport activity, and Delta20 abolishes insertion and
      activity. By expressing Delta12 or Delta20 in two halves, both expression and
      activity are restored to levels approximating wild type. Replacing deleted
      residues with random hydrophilic amino acids also leads to full recovery.
      However, introduction of hydrophobic residues decreases expression and activity
      in a context-dependent manner. Thus, a minimum length of the central cytoplasmic
      loop is vital for proper insertion, stability, and efficient transport activity,
      because of constraints at the cytoplasmic ends of helices VI and VII.
      Furthermore, the results are consistent with the idea that the middle cytoplasmic
      loop provides a temporal delay between insertion of the first six helices into
      the membrane before insertion of the second six helices.

PMID- 10880571
TI  - whmD is an essential mycobacterial gene required for proper septation and cell
      division.
AB  - A study of potential mycobacterial regulatory genes led to the isolation of the
      Mycobacterium smegmatis whmD gene, which encodes a homologue of WhiB, a
      Streptomyces coelicolor protein required for sporulation. Unlike its Streptomyces
      homologue, WhmD is essential in M. smegmatis. The whmD gene could be disrupted
      only in the presence of a plasmid supplying whmD in trans. A plasmid that allowed
      chemically regulated expression of the WhmD protein was used to generate a
      conditional whmD mutant. On withdrawal of the inducer, the conditional whmD
      mutant exhibited irreversible, filamentous, branched growth with diminished
      septum formation and aberrant septal placement, whereas WhmD overexpression
      resulted in growth retardation and hyperseptation. Nucleic acid synthesis and
      levels of the essential cell division protein FtsZ were unaltered by WhmD
      deficiency. Together, these phenotypes indicate a role for WhmD in mycobacterial
      septum formation and cell division.

PMID- 10880572
TI  - Orbitofrontal cortex: A key prefrontal region for encoding information.
AB  - Little is known about the specific functional contribution of the human
      orbitofrontal cortex with regard to memory processing, although there is strong
      evidence from lesion studies in monkeys that it may play an important role. The
      present investigation measured changes in regional cerebral blood flow with
      positron emission tomography in normal human subjects who were instructed to
      commit to memory abstract visual patterns. The results indicated that the rostral
      orbitofrontal region (area 11), which is primarily linked with the anterior
      medial temporal limbic region and lateral prefrontal cortical areas, is involved
      in the process of encoding of new information.

PMID- 10880573
TI  - Reelin controls position of autonomic neurons in the spinal cord.
AB  - Mutation of the reeler gene (Reln) disrupts neuronal migration in several brain
      regions and gives rise to functional deficits such as ataxic gait and trembling
      in the reeler mutant mouse. Thus, the Reln product, reelin, is thought to control
      cell-cell interactions critical for cell positioning in the brain. Although an
      abundance of reelin transcript is found in the embryonic spinal cord [Ikeda, Y. &
      Terashima, T. (1997) Dev. Dyn. 210, 157-172; Schiffmann, S. N., Bernier, B. &
      Goffinet, A. M. (1997) Eur. J. Neurosci. 9, 1055-1071], it is generally thought
      that neuronal migration in the spinal cord is not affected by reelin. Here,
      however, we show that migration of sympathetic preganglionic neurons in the
      spinal cord is affected by reelin. This study thus indicates that reelin affects
      neuronal migration outside of the brain. Moreover, the relationship between
      reelin and migrating preganglionic neurons suggests that reelin acts as a barrier
      to neuronal migration.

PMID- 10880574
TI  - Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic
      peptide-converting enzyme.
AB  - Atrial natriuretic peptide (ANP) is a cardiac hormone essential for the
      regulation of blood pressure. In cardiac myocytes, ANP is synthesized as a
      precursor, pro-ANP, that is converted to biologically active ANP by an unknown
      membrane-associated protease. Recently, we cloned a transmembrane serine
      protease, corin, that is highly expressed in the heart. In this study, we examine
      effects of corin on pro-ANP processing. Our results show that recombinant human
      corin converts pro-ANP to ANP and that the cleavage in pro-ANP by corin is highly
      sequence specific. Our findings suggest that corin is the long-sought pro-ANP
      converting enzyme and that the corin-mediated pro-ANP activation may play a role
      in regulating blood pressure.

PMID- 10880575
TI  - V(D)J recombination is not activated by demethylation of the kappa locus.
AB  - V(D)J recombination is thought to be regulated by changes in the accessibility of
      target sites, such as modulation of methylation. To test whether demethylation of
      the kappa locus can activate recombination, we generated two recombinationally
      active B cell lines in which the gene for maintenance of genomic DNA methylation,
      Dnmt1, was flanked with loxP sites. Transduction with a retrovirus expressing
      both the cre recombinase and green fluorescent protein allowed us to purify
      recombinationally active cells devoid of methylation. Loss of methylation of the
      kappa locus was not sufficient to activate recombination, although transcription
      was activated in one line. It appears that demethylation of the kappa locus is
      not the rate-limiting step for altering accessibility and thus regulated
      demethylation does not generate specificity of recombination.

PMID- 10880577
TI  - The decomposition of peroxynitrite does not yield nitroxyl anion and singlet
      oxygen.
AB  - In a recent article [Khan, A. U., Kovacic, D., Kolbanovsky, A., Desai, M.,
      Frenkel, K. & Geacintov, N. E. (2000) Proc. Natl. Acad. Sci. USA 97, 2984-2989],
      the authors claimed that ONOO(-), after protonation to ONOOH, decomposes into
      (1)HNO and (1)O(2) according to a spin-conserved unimolecular mechanism. This
      claim was based partially on their observation that nitrosylhemoglobin is formed
      via the reaction of peroxynitrite with methemoglobin at neutral pH. However,
      thermochemical considerations show that the yields of (1)O(2) and (1)HNO are
      about 23 orders of magnitude lower than those of ( small middle dot)NO(2) and (
      small middle dot)OH, which are formed via the homolysis of ONOOH. We also show
      that methemoglobin does not form with peroxynitrite any spectrally detectable
      product, but with contaminations of nitrite and H(2)O(2) present in the
      peroxynitrite sample. Thus, there is no need to modify the present view of the
      mechanism of ONOOH decomposition, according to which initial homolysis into a
      radical pair, [ONO( small middle dot) ( small middle dot)OH](cage), is followed
      by the diffusion of about 30% of the radicals out of the cage, while the rest
      recombines to nitric acid in the solvent cage.

PMID- 10880651
TI  - The application of psychosomatic research to clinical cardiology

PMID- 10880576
TI  - High-resolution microPET imaging of carcinoembryonic antigen-positive xenografts
      by using a copper-64-labeled engineered antibody fragment.
AB  - Rapid imaging by antitumor antibodies has been limited by the prolonged targeting
      kinetics and clearance of labeled whole antibodies. Genetically engineered
      fragments with rapid access and high retention in tumor tissue combined with
      rapid blood clearance are suitable for labeling with short-lived radionuclides,
      including positron-emitting isotopes for positron-emission tomography (PET). An
      engineered fragment was developed from the high-affinity anticarcinoembryonic
      antigen (CEA) monoclonal antibody T84.66. This single-chain variable fragment
      (Fv)-C(H)3, or minibody, was produced as a bivalent 80 kDa dimer. The macrocyclic
      chelating agent 1,4,7, 10-tetraazacyclododecane-N,N',N", N"'-tetraacetic acid
      (DOTA) was conjugated to the anti-CEA minibody for labeling with copper-64, a
      positron-emitting radionuclide (t(1/2) = 12.7 h). In vivo distribution was
      evaluated in athymic mice bearing paired LS174T human colon carcinoma (CEA
      positive) and C6 rat glioma (CEA negative) xenografts. Five hours after injection
      with (64)Cu-DOTA-minibody, microPET imaging showed high uptake in CEA-positive
      tumor (17.9% injected dose per gram +/- 3.79) compared with control tumor (6.0%
      injected dose per gram +/- 1.0). In addition, significant uptake was seen in
      liver, with low uptake in other tissues. Average target/background ratios
      relative to neighboring tissue were 3-4:1. Engineered antibody fragments labeled
      with positron-emitting isotopes such as copper-64 provide a new class of agents
      for PET imaging of tumors.

PMID- 10880578
TI  - NMR investigation of ferricytochrome c unfolding: detection of an equilibrium
      unfolding intermediate and residual structure in the denatured state.
AB  - Horse ferricytochrome c (cyt c) undergoes exchange of one of its axial heme
      ligands (Met-80) for one or more non-native ligands under denaturing conditions.
      We have used (1)H NMR spectroscopy to detect two conformations of paramagnetic
      cyt c with non-native heme ligation through a range of urea concentrations. One
      non-native form is an equilibrium unfolding intermediate observed under partially
      denaturing conditions and is attributed to replacement of Met-80 with one or more
      Lys side chains. The second non-native form, in which the native Met ligand is
      replaced by a His, is observed under strongly denaturing conditions.
      Thermodynamic analysis of these data indicates a relatively small DeltaG (17
      kJ/mol) for the transition from native to the Lys-ligated intermediate and a
      significantly larger DeltaG (47 kJ/mol) for the transition from native to the His
      ligated species. Although CD and fluorescence data indicate that the equilibrium
      unfolding of cyt c is a two-state process, these NMR results implicate an
      intermediate with His-Lys ligation.

PMID- 10880652
TI  - The significance of this special issue.

PMID- 10880653
TI  - The current status of heart-mind relationships.

PMID- 10880654
TI  - Research as a basis for clinical care.

PMID- 10880655
TI  - Going to the heart of the matter: do negative emotions cause coronary heart
      disease?
AB  - OBJECTIVE: Negative emotions, such as anger, anxiety, and depression, have
      emerged as potentially important risk factors for coronary heart disease. The
      purpose of this article is to consider the nature and function of emotions, to
      review epidemiological evidence for an association between the three negative
      emotions and coronary heart disease (CHD), to discuss briefly the mechanisms by
      which emotions may be linked to CHD, and to consider this evidence in light of
      theoretical insights provided by mainstream psychological research on emotions.
      METHODS: We collected articles published between 1980 and 1998 on the
      relationship between each negative emotion and CHD. We also collected review
      articles or chapters published during the same time period that considered
      mechanisms by which emotions may increase CHD risk. We used a qualitative
      approach to review the published literature. RESULTS: Evidence that anxiety is
      involved in the onset of CHD is strongest, whereas evidence for an association
      between anger and CHD is limited but suggestive. Although depression has
      consistently been linked to mortality following a myocardial infarction, evidence
      for its role in the onset of coronary disease is quite mixed. Numerous unresolved
      issues leave our current understanding of the emotion-health relationship
      incomplete. Psychological theories of emotion are considered to help address gaps
      in our knowledge. CONCLUSION: Growing evidence indicates that negative emotions
      may influence the development of CHD. The focused and specific consideration of
      negative emotions and their possible role in the etiology of CHD gives insight
      into current knowledge and suggests important directions for future research.

PMID- 10880656
TI  - Biobehavioral factors in the context of ischemic cardiovascular diseases.
AB  - OBJECTIVE: We set out to examine the development of current thinking on the
      relationship between behavioral factors and ischemic heart disease, with the
      latter being viewed as an epidemic. METHODS: The present work is a nonsystematic
      review of the subject. RESULTS: Atherogenic components of the coronary-prone or
      type A behavior pattern (TABP), including hostility, cynicism, and suppression of
      anger, as well as stress reactivity, depression, and social isolation, are
      emerging as particularly significant behavioral characteristics, although their
      pathophysiology is not yet fully understood. Effective patient management,
      particularly for lifestyle modification, requires an appreciation of an
      individual's stage in their readiness to change. CONCLUSION: The control and
      prevention of cardiovascular diseases depend on a multidisciplinary approach that
      recognizes the importance and intricacies of lifestyle behaviors.

PMID- 10880657
TI  - Is panic disorder associated with coronary artery disease? A critical review of
      the literature.
AB  - OBJECTIVE: To critically review existing literature examining the relationship
      between panic disorder (PD) and coronary artery disease (CAD). We specifically
      sought answers to the following questions: (1) What is the prevalence of PD in
      CAD patients? (2) What is the directionality of the relationship between PD and
      CAD? (3) What mechanisms may mediate the link between PD and CAD? METHODS:
      Medline and Psychlit searches were conducted using the following search titles:
      "panic disorder and coronary artery disease", "panic disorder and coronary heart
      disease", and "panic disorder and cardiovascular disease" for the years 1980
      1998. The above search was also repeated replacing "panic disorder" with "panic
      attacks" for the same period. RESULTS: The prevalence of PD in both cardiology
      out-patients and patients with documented CAD ranges from 10% to 50%. The
      association between PD and CAD appeared strongest in patients with atypical chest
      pain or symptoms that could not be fully explained by coronary status. There is
      some evidence linking phobic anxiety but not PD per se to CAD risk, but little
      evidence linking CAD to PD risk. Studies of the mechanisms linking PD to CAD are
      still in their infancy, but there is preliminary evidence linking PD to reduced
      heart rate variability (HRV) and myocardial ischemia, two pathophysiological
      mechanisms related to CAD. CONCLUSION: PD is prevalent in CAD patients, but it is
      unclear the extent to which PD confers risk for and/or exacerbates CAD.
      Prospective research is needed to more firmly establish PD as a distinct risk
      factor for the development and progression of CAD. However, because many of the
      symptoms of PD mimic those of CAD, differentiating these disorders and learning
      how they may influence each other is imperative for clinical practice.

PMID- 10880658
TI  - Psychological factors affecting a medical condition: ischemic coronary heart
      disease.
AB  - The criteria for scientific validation of the entities currently subsumed under
      the DSM-IV category of "Psychological Factors Affecting a Medical Condition" have
      never been clearly enumerated. Historically, its precursor category
      ("Psychophysiological Disorder") was rarely used, and predicated upon clinical
      observation of personality styles among patients with specific physical
      illnesses, or clinical observations relating psychosocial events and symptom
      exacerbation. Because of logical flaws with either of these methods,
      clarification of the most rigorous criteria for demonstrating a cause-effect
      relationship is necessary. With the increase in well-designed and carefully
      executed epidemiological and treatment studies, this diagnostic category has
      evolved into an arena where cutting-edge insights and therapies are becoming
      available for a growing variety of medical conditions, especially ischemic
      coronary heart disease. The present article reviews the nature of the scientific
      evidence necessary to accept an etiological or aggravating role for psychological
      events.

PMID- 10880659
TI  - An historical context for behavioral models of hypertension.
AB  - OBJECTIVE: The purpose of this study is provide an historical context for current
      behavioral models of hypertension. METHODS: A selective sample of the
      cardiovascular reactivity literature was reviewed, from 1932 to present. RESULTS:
      In the earliest model, cardiovascular reactivity was regarded as a marker of
      disease risk; however, in later models, reactivity came to be viewed as a causal
      influence in the development of hypertension. As the models evolved, the
      underlying assumptions changed. Thus, the risk marker model assumed that
      cardiovascular responses to stress were a stable, generalized characteristic of
      the individual, and therefore the eliciting stimuli were arbitrary. The later
      models, however, assume that the nature of the eliciting stimulus is a
      determinant of the cardiovascular response. We describe the increasing complexity
      of the four models, and contrast their underlying assumptions and the
      implications of these assumptions. CONCLUSION: We provide an overview of study
      designs and variables that should be incorporated into studies seeking to
      understand the ways in which cardiovascular responses to stress may influence the
      development of hypertension.

PMID- 10880660
TI  - Depression in patients with cardiac disease: a practical review.
AB  - Some degree of depression affects at least 30% of hospitalized patients with
      coronary artery disease (CAD), and is associated with increased risks of
      mortality and continuing depression over at least the first year following
      hospital discharge. Despite its consequences for prognosis and quality of life,
      depression is underrecognized and undertreated in cardiac patients. The diagnosis
      of depression is complicated in patients with medical illness. Their symptoms can
      reflect physical as well as psychological complaints. Many CAD patients resist
      the idea of additional medications, and drug interactions can be problematic for
      those willing to accept antidepressant treatment. Finally, depression tends to
      recur. Its successful treatment requires a long-term commitment from both
      physician and patient. This article examines the special challenges involved in
      diagnosing depression in patients with CAD, outlines available psychotherapeutic
      and pharmacological treatments, and considers the issues involved in deciding
      which patients to treat, with what approach, and for how long.

PMID- 10880661
TI  - Panic disorder and the heart: a cardiology perspective.
AB  - Panic disorder is a common condition that includes symptoms that may masquerade
      as a primary cardiovascular disorder. In addition, many patients with
      cardiovascular disease may also have panic disorder. To date, no definitive
      pathophysiological mechanism for panic disorder has been found; however, there
      are several hypotheses in the literature. Patients with syndrome X, coronary
      artery disease and/or palpitations, in addition to panic disorder all present to
      cardiologists. However, many patients go undiagnosed and ultimately place large
      costs on the health care system as a result. Panic disorder is a treatable
      condition, and cardiologists could easily identify patients with panic disorder
      and initiate appropriate therapy and/or referral.

PMID- 10880662
TI  - Assessment of quality of life in patients with cardiac disease: the role of
      psychosomatic medicine.
AB  - OBJECTIVE: The measurement of quality of life has become important in evaluating
      new treatments of cardiac disease. This review focuses on definition and general
      concepts underlying quality of life in patients with cardiac disease, the ways in
      which it is measured, and the uses and limitations of quality-of-life
      measurement. METHODS: A Medline search, from 1988 to 1998, was undertaken using
      the search terms "cardiovascular disease and quality of life" and "cardiovascular
      disease and health status." Results of clinical trials of cardiovascular
      therapies using quality-of-life instruments were not reviewed. RESULTS: Quality
      of life is defined as "...the functional effect of an illness and its consequent
      therapy upon a patient, as perceived by the patient." Domains of quality of life
      include physical, mental, social, and occupational function; health perceptions;
      and symptoms of disease. CONCLUSION: Psychosomatic medicine contributions to
      understanding patients' reactions to physical illness and injury may offer
      enhanced insight into assessment of health perceptions. Generic health profiles
      and cardiac-disease-specific quality-of-life measures would also be useful in
      psychosomatic investigations of personality, hostility, depression, and social
      isolation in patients with cardiac disease.

PMID- 10880663
TI  - Gender and psychosomatic aspects of ischemic heart disease.
AB  - While women and their doctors have traditionally worried about mortality from
      breast and gynecological malignancies, over the past 5 years they have come to
      realize that ischemic cardiac disease (IHD) is the number one killer of women in
      most Western countries. This has led to public and professional education
      campaigns and a new emphasis on gender and gender-specific research in IHD.
      Unfortunately, this literature remains poorly developed and much work remains to
      be done. Even in samples in which there may be sufficient numbers to allow for
      the evaluation of gender and gender differences, these important analyses have
      often been overlooked. This article provides a review of what is known about
      gender and gender differences in psychosocial and behavioral issues in IHD.

PMID- 10880664
TI  - Risk factor modification through nonpharmacological interventions in patients
      with coronary heart disease.
AB  - Coronary heart disease (CHD) is still the main cause of death in developed
      countries. Because of improved treatment, many patients survive the acute phase
      of a myocardial infarction, which makes secondary prevention of CHD of major
      importance. Most risk factors responsible for the development and progression of
      CHD are associated with behavior. Therefore, interventions aimed at behavior
      change may contribute to risk factor modification and secondary prevention of
      CHD. The effects of separate risk factor modification efforts by means of
      randomized, controlled clinical trials of nonpharmacological interventions in
      patients suffering from CHD are reviewed. Interventions aimed at healthy
      lifestyles may stimulate smoking cessation rates, reduce elevated serum total and
      low-density lipoprotein (LDL)-cholesterol concentrations, and favorably modify
      type A behavior in CHD patients. Moreover, reduction of coronary atherosclerosis
      has been reported after intensive lifestyle and exercise interventions, whereas
      exercise and type A interventions may also lead to reduced CHD morbidity and
      mortality. As for hypertension and obesity, studies aimed at secondary prevention
      are lacking.

PMID- 10880665
TI  - Psychological treatments in cardiac rehabilitation: review of rationales and
      outcomes.
AB  - OBJECTIVE: In this review, the place of psychological interventions in cardiac
      rehabilitation and differences in underlying rationales are presented. Treatment
      approaches vary in that some practitioners favor biobehavioral approaches with
      strong relaxation/breathing components, whereas others offer unstructured
      support, psychoeducation to maximize compliance, or psychological interventions
      directed at reducing emotional distress. METHODS: The effectiveness of
      psychosocial rehabilitation for endpoints like mortality, recurrence, emotional
      distress, and intermediate hard endpoints is reviewed by integrating conclusions
      from narrative and meta-analytic reviews as well as recent major clinical trials.
      RESULTS: The aggregated findings support the use of psychosocial interventions
      and they also help to explain critical differences in outcome in that studies
      which fail to reduce distress also fail to lead to reduced mortality or reduced
      event recurrence. CONCLUSION: Gender differences in outcome and recent trends in
      cardiology are discussed because both have distinct consequences for the
      effective delivery of psychological services to cardiac patients.

PMID- 10880666
TI  - Effects of anxiety and depression on 5-year mortality in 5,057 patients referred
      for exercise testing.
AB  - OBJECTIVE: Beyond acute myocardial infarction, little is known about the effect
      of depression, and especially anxiety, on prognosis in cardiology patients. The
      present study aims to examine the effect of anxiety and depression on 5-year
      mortality in patients referred for exercise testing. METHODS: A total of 5,057
      patients referred for routine exercise testing completed the Hospital Anxiety and
      Depression Scale (HADS) before undergoing the exercise test. Survival data were
      obtained from 5,017 (99.2%) of those patients after 5.7 +/- 0.8 years. HADS
      scores and cardiological baseline data were used to predict mortality. RESULTS:
      In univariate analyses, HADS depression was not a significant predictor; high
      anxiety was associated with improved survival. Logistic regression revealed nine
      independent objective predictors from which we computed a composite somatic risk
      index. When controlling for this physical risk index, anxiety and depression had
      independent, opposite effects; that is, anxiety was associated with a lower
      mortality and depression with a higher mortality. CONCLUSION: Anxiety and
      depression scores have different predictive effects on mortality in patients
      referred for exercise testing. These effects are independent of a highly
      effective physical risk index, suggesting that psychological screening of
      cardiology patients might improve risk stratification.

PMID- 10880667
TI  - Behavioral risk factors of sudden cardiac arrest.
AB  - OBJECTIVE: The purpose of this study was to investigate the association between
      sudden cardiac arrest (SCA) and the behavioral factors exhaustion and
      nonexpression of emotions. METHODS: Case-control study of 99 victims of SCA and
      119 coronary controls, matched for gender and age. RESULTS: Victims of SCA were
      more often assessed as exhausted and as closed by their family members than
      controls. A significant interaction between exhaustion and closeness on the risk
      of SCA was observed. Those who were exhausted and did not express their emotions
      had a sevenfold greater risk of SCA. CONCLUSION: The behavioral factor of
      exhaustion and nonexpression of emotions may contribute to the identification of
      persons at elevated risk for SCA.

PMID- 10880668
TI  - Depression and health-care costs during the first year following myocardial
      infarction.
AB  - OBJECTIVE: Depression in the hospital after myocardial infarction (MI) has been
      associated with a substantial increase in the long-term risk of cardiac
      mortality, but little is known about other outcomes. This study uses Quebec
      Medicare data to examine the relationship between post-MI depression and
      physician costs, including both out-patient care and hospital readmissions.
      METHODS: The sample consists of 848 1-year survivors of an acute MI who had
      completed the Beck Depression Inventory (BDI) in hospital. Two hundred sixty
      subjects had BDI scores of >/=10 (30.7%), indicative of mild to moderate symptoms
      of depression. Quebec Medicare data during the index admission for an acute MI
      and during the year following discharge were compared for the patients with
      elevated BDI scores and those with normal scores. RESULTS: Total costs, in
      Canadian dollars (out-patient physician charges plus physician costs during
      admissions plus estimates of associated direct costs), were about 41% higher (p =
      0.004) for patients with elevated BDI scores. The difference was primarily
      related to out-patient and emergency room visits and readmission costs associated
      with longer stays in hospital wards, and was not accounted for by use of
      psychiatric services or readmissions for revascularization. CONCLUSION: Results
      suggest that, in addition to the survival risks associated with post-MI
      depression, there are increased health care costs linked to both readmissions and
      out-patient contacts among depressed patients who survive the first post-MI year.
      The extent to which the increased use of health care may have reduced depression
      and enhanced survival remains unclear.

PMID- 10880669
TI  - Decreased health care use among patients with silent myocardial ischemia: support
      for a generalized rather than cardiac-specific silence.
AB  - OBJECTIVE: The absence of angina among patients with silent myocardial ischemia
      (SMI) may be a cardiac phenomenon or may reflect a generalized lack of bodily
      awareness and symptom reporting. We tested the hypothesis that the silence is
      generalized, and, therefore, that patients with SMI would make fewer health care
      visits for noncardiac/chest-pain problems than patients with symptomatic
      ischemia. METHODS: We counted all out-patient visits to our medical system for
      the prior 18 months for 95 patients who demonstrated ischemia during treadmill
      exercise testing and subsequent nuclear scanning: 62 of the patients had SMI
      during exercise, and 33 of the patients had symptomatic ischemia. RESULTS:
      Patients with SMI made were significantly less likely to have sought emergency
      care or primary care and had significantly fewer primary care visits than
      patients with symptomatic ischemia. Group differences remained after controlling
      for demographics and health status variables. The two groups did not differ on
      utilization of specialty care. CONCLUSION: The reduced use of emergency and
      primary care among patients with SMI suggests that they have a generalized rather
      than cardiac-specific reduction in somatic awareness and/or symptom reporting.

PMID- 10880670
TI  - Cerebral activation, hostility, and cardiovascular control during mental stress.
AB  - OBJECTIVE: Hostility has been established as a risk factor for the development of
      coronary artery disease. Putatively pathogenic hemodynamic and neuroendocrine
      responses to psychological stressors are associated with hostility, but the
      cerebral effects of hostility and their relationship to these responses are
      unknown. This pilot study examined cardiovascular and cerebral blood flow
      responses to stress in subjects with high and low levels of trait hostility.
      METHODS: Regional cerebral blood flow was measured by single-photon emission
      computed tomography (SPECT) during a control condition and in response to mental
      arithmetic stress. RESULTS: The stressor was associated with reduced blood flow
      to the prefrontal cortex, and this reduction was greater in the high hostility
      subjects. CONCLUSION: These preliminary findings support the hypothesis that
      mental arithmetic stress is associated with reduced blood flow to prefrontal
      cortex, and that trait hostility is associated with a stronger effect.

PMID- 10880671
TI  - Severe depression is associated with markedly reduced heart rate variability in
      patients with stable coronary heart disease.
AB  - OBJECTIVE: The purpose of this study was to investigate the relationship between
      depression and heart rate variability in cardiac patients. METHODS: Heart rate
      variability was measured during 24-hour ambulatory electrocardiographic (ECG)
      monitoring in 40 medically stable out-patients with documented coronary heart
      disease meeting current diagnostic criteria for major depression, and 32
      nondepressed, but otherwise comparable, patients. Patients discontinued beta
      blockers and antidepressant medications at the time of study. Depressed patients
      were classified as mildly (n = 21) or moderately-to-severely depressed (n = 19)
      on the basis of Beck Depression Inventory scores. RESULTS: There were no
      significant differences among the groups in age, gender, blood pressure, history
      of myocardial infarction, diabetes, or smoking. Heart rates were higher and
      nearly all indices of heart rate variability were significantly reduced in the
      moderately-to-severely versus the nondepressed group. Heart rates were also
      higher and mean values for heart rate variability lower in the mildly depressed
      group compared with the nondepressed group, but these differences did not attain
      statistical significance. CONCLUSION: The association of moderate to severe
      depression with reduced heart rate variability in patients with stable coronary
      heart disease may reflect altered cardiac autonomic modulation and may explain
      their increased risk for mortality.

PMID- 10880672
TI  - Gender differences in emotional disability and negative health perception in
      cardiac patients 6 months after stent implantation.
AB  - OBJECTIVES: In this study we evaluate gender differences in affective adaptation
      and health perception in patients 6 months after stent implantation. BACKGROUND:
      Assessment of gender-specific behavioral strategies to cope with serious cardiac
      disease conditions has not been given much attention until now. Preliminary data
      suggest greater impairments in female patients, which might be of clinical
      relevance. METHODS: Three hundred seventeen patients were eligible for the 6
      month follow-up investigation, 78 (24.6%) of whom were women. The women were
      significantly older but did not differ from men in their cardiac risk features
      and treatment procedures. There were no gender differences in prevalence of
      hypertension, hypercholesterolemia, and family history. Men had a significantly
      higher prevalence of smoking than women, whereas women had a significantly higher
      prevalence of diabetes than men. A structured interview and a standardized
      psychodiagnostic assessment was carried out, which covered domains of affective
      dysfunction (depression, anxiety, intrusion, and avoidance), vegetative symptoms
      (sleeping disorders), and parameters of negative health perception. RESULTS:
      There were no significant gender differences in the prevalence of depressive
      symptoms. Women exhibited higher mean values of anxiety than men, which did not
      reach significance. Sleeping disorders were significantly more prevalent in
      women. The absolute level of being distressed by intrusive thoughts and avoidance
      behavior related to the severe underlying disease process was low in the total
      group of patients examined. Measurable gender differences did not emerge. Fifty
      one (16.5%) patients exhibited pessimistic anticipation of dire consequences and
      severe signs of negative health perception (NHP group). There was a trend,
      although not statistically significant, toward more women being in the NHP group.
      The distribution of cardiac risk factors, however, was completely balanced in the
      NHP(+) and NHP(-) patient groups. Objective somatic cardiac disease parameters
      did not account for the negative health perception. NHP was, however, associated
      with significantly more prestent angina pectoris (p < 0.040) and poststent angina
      pectoris (p < 0.0001). High levels of anxiety, depression, and of disturbed sleep
      also led to a sharp separation between patients with high degrees of an
      anticipated incapacitation due to the disease process. Univariate regression
      analysis suggested an effect of female gender on the occurrence of NHP (odds
      ratio 1. 70; 95% CI 0.88 to 3.25), which was of borderline significance. Control
      for confounders in a multiple regression model, however, eliminated the gender
      effect (odds ratio 1.04, 95% CI 0.48 to 2.23). Poststent chest pain (odds ratio
      7.75, 95% CI 3.28 to 18.32) and sleeping disorders (odds ratio 1.32, 95% CI 1.16
      to 1.51) were identified as the most powerful confounders of the gender-NHP
      association. CONCLUSION: Contrary to expectation, women were not per se more
      distressed than men in all areas of adaptation of the midterm course after stent
      implantation, although the higher levels of anxiety and sleeping disorders in
      women deserve attention. A considerable proportion of patients exhibited a
      pessimistic disease perspective independent of their somatic status, which was
      associated with affective morbidity. The tendency toward more negative health
      perception in women may be due to their more frequent occurrence of chest pain
      and sleeping disorders.

PMID- 10880673
TI  - Dopamine-acetylcholine interaction in the rat lateral hypothalamus in the control
      of locomotion.
AB  - Pharmacological, neurochemical, and behavioral techniques were used to
      characterize DA-ACh interaction within the lateral hypothalamus (LH) in the
      context of locomotion, feeding behavior, and reinforcement. In Experiment 1, the
      muscarinic agonist carbachol injected in the LH increased locomotor activity in
      proportion to dose. In Experiment 2, the same doses of carbachol proportionately
      increased exctracellular DA in the nucleus accumbens (Nac) as monitored by brain
      microdialysis. Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
      also increased. In Experiment 3, LH infusion by reverse microdialysis of the D(2)
      receptor blocker sulpiride released ACh in the LH in a dose-response manner. This
      suggested that sulpiride disinhibits ACh release via D(2) receptors in the LH and
      thereby facilitates behavior. Confirming this in Experiment 4, local LH atropine
      5 min before sulpiride suppressed the locomotor response to sulpiride for about
      20 min. These results suggest that sulpiride acts in the LH by disinhibiting a
      hypothalamic locomotor mechanism that is cholinergically driven and connected
      with the mesoaccumbens dopamine pathway. Given prior results that local sulpiride
      in the LH can induce hyperphagia and reward, this system may be involved in
      searching for food and rewarding feeding behavior. In conclusion, DA acts in the
      LH via D(2) receptors to inhibit cholinergic neurons or terminals that are part
      of an approach system for eating.

PMID- 10880674
TI  - Chronic corticosterone impairs inhibitory avoidance in rats: possible link with
      atrophy of hippocampal CA3 neurons.
AB  - The aim of our work was to evaluate the effect of a chronic (22 days)
      administration of corticosterone, which induces supraphysiological serum levels
      of the hormone, on an inhibitory avoidance learning in rats (one-trial step
      through learning task, footshock: 0.5 mA, 2 s). We also studied hippocampal
      markers of neuroanatomical CA3 pyramidal neuron atrophy by using the Golgi
      staining method. Chronic exposure to high CORT serum levels induced a significant
      impairment of inhibitory avoidance learning. The CORT group also showed
      hippocampal glucocorticoid receptor (GR) downregulation and the decrease of
      hippocampal CA3 branch points and total dendritic length in the apical tree that
      would be causally related with the learning impairment.

PMID- 10880675
TI  - Sensitivity to ethanol-induced motor incoordination in FAST and SLOW selectively
      bred mice.
AB  - Earlier studies using the grid test have indicated a negative genetic correlation
      between sensitivity to ethanol-induced locomotor stimulation and ethanol-induced
      motor incoordination in FAST and SLOW mice, lines selectively bred for
      differential sensitivity to ethanol's stimulant effects. Because different tests
      of motor coordination may not measure the same behavioral competencies or
      physiological substrates, the present experiments tested adult ethanol- or saline
      exposed FAST and SLOW mice of two replicates (FAST-1, FAST-2, SLOW-1, and SLOW-2)
      using three additional tests of coordination: a stationary dowel, fixed-speed
      rotarod, and accelerating rotarod. After ethanol treatment, FAST-1 mice fell from
      the stationary dowel at shorter latencies than SLOW-1 mice, suggesting that they
      had relatively greater sensitivity to ethanol. However, brain ethanol
      concentrations (BrECs) were similar at time of fall, and no differences were
      found between replicate-2 lines. SLOW-1 mice fell from the fixed-speed rotarod at
      lower BrECs than FAST-1 mice, suggesting possibly greater sensitivity of the SLOW
      1 line. Again, no replicate-2 line differences were found. No significant
      differences were detected for the accelerating rotarod. These results provide
      little support for a negative genetic relationship between sensitivity to the
      stimulant and ataxic effects of ethanol using these measures of motor
      coordination.

PMID- 10880676
TI  - Cocaine-induced sniffing stereotypy changes in response to threat.
AB  - "Cocaine-induced stereotypies" have been extensively investigated on the basis
      that they may be capable of providing insights into behavioral and neurochemical
      mechanisms relevant to drug abuse and addiction. Recent work has indicated that
      cocaine enhances a number of defensive behaviors, and, that cocaine-enhanced
      sniffing may be a functional behavior pattern, potentially related to defense,
      prompting an investigation of the effects of threat stimuli on cocaine-enhanced
      sniffing. When behaviors of saline control rats were evaluated in their home
      cages (HC), or on exposure to a toy cat (TC) or real cat (RC), they showed
      minimal crouching in the HC; initial crouching declining over 5 days of
      repetitions to the TC; and continued, high-level crouching to the RC. Cocaine (30
      mg/kg, IP) enhanced defensiveness in situations in which it had declined in the
      TC and RC groups. It also produced high-level sniffing, declining over 5 test
      days, in the HC; initial low-level sniffing to the TC, increasing over 5 test
      days; and very low levels of sniffing to the RC. These and previous data
      contribute to a view that cocaine enhances, but does not directly induce,
      defensive behaviors. They also indicate that external threat stimuli such as the
      RC, or initial presentation of the TC suppress sniffing, with sniffing returning
      as habituation to novel but not intrinsically dangerous stimuli reduces
      defensiveness. This view suggests that some component of "sensitization of
      cocaine-induced sniffing stereotypy" may reflect a release from defensiveness
      mediated suppression of sniffing over repeated injection/testing as the subject
      becomes habituated to the injection procedure and to novel test situations.

PMID- 10880677
TI  - Methylxanthines reverse the adipsic and aphagic syndrome induced by bilateral 6
      hydroxydopamine lesions of the nigrostriatal pathway in rats.
AB  - This study investigated whether methylxanthines (caffeine and theophylline) would
      restore food and water intake in rats made aphagic and adipsic by bilateral 6
      hydroxydopamine lesions of the nigrostriatal bundle, and these results were
      compared with the effects of d-amphetamine, the dopamine D(1) agonist SKF 38393,
      and the D(2/3) agonist quinpirole. In a separate experiment, we investigated
      whether the selective D(1) antagonist, SCH 23390, or the selective D(2)
      antagonist, sulpiride, would prevent the caffeine-induced restoration of food and
      water intake in bilaterally 6-hydroxydopamine denervated rats. The results showed
      that caffeine, theophylline, and quinpirole significantly reversed the aphagia
      and adipsia observed in lesioned animals. SKF 38393 had no significant effects on
      water intake, while it significantly restored food intake at the highest dose
      used. In contrast, d-amphetamine had no significant effects on food or water
      intake. Results from the second experiment showed that sulpiride attenuated the
      caffeine-induced restoration of food and water intake in lesioned rats to a
      greater extent than did SCH 23390. These data suggest that methylxanthines may
      mediate their effects on food and water intake in bilateral 6-hydroxydopamine
      lesioned rats through an action at the dopaminergic system.

PMID- 10880678
TI  - Effect of flumazenil and diazepam on transient actions in defensive burying
      elicited by the social interaction experience in rats.
AB  - In the present work, we studied the effects of benzodiazepine (BZ) receptor
      antagonist, flumazenil, and of the agonist, diazepam, on social interaction
      induced transient changes in defensive burying (DB). Enhanced defensive burying
      was observed after 1.5 min of social interaction experience, while a longer
      social interaction experience, 15 min, inhibited the expression of burying
      behavior. Defensive burying and social interaction paradigms have been used for
      the screening of compounds with anxiolytic potential and, more extensively, to
      study the neurobiology of anxiety. To elucidate the participation of the BZ
      receptor on transient changes induced by intervals of social interaction
      experience, its receptor antagonist, flumazenil (2.5, 5, and 10 mg/kg) was
      intraperitoneally injected (IP). Flumzenil enhanced in a dose-dependent manner,
      the blocking effect of the saline IP injection on facilitated DB in 1.5-min
      social interaction-experienced subjects. In addition, flumazenil enlarged in a
      dose-dependent manner the blocking effect of saline IP on defensive burying
      levels in animals exposed to social interaction experience for 15 min. To analyze
      the presumed participation of the BZ receptor mediating enhanced burying behavior
      levels in subjects exposed to 1.5 min of social interaction, a suboptimal dose of
      diazepam (0.25 mg/kg) was administered. Diazepam enhanced the saline IP elicited
      defensive burying reduction. Results are discussed in terms of the suggested BZ
      receptor mediation on transient changes in defensive burying elicited by social
      interaction experience.

PMID- 10880679
TI  - Acute effects of nalmefene on LH, prolactin, and testosterone in male rhesus
      monkeys.
AB  - The effects of the long-acting opioid antagonist, nalmefene [17-N
      cyclopropylmethyl-3,14-beta-dihydroxy-4, 5-alpha-epoxy-6-methylene morphinan
      hydrochloride] on LH, T, and prolactin release in rhesus monkeys are unknown. The
      acute effects of nalmefene (0.01 and 0.10 mg/kg, IV) or placebo on LH, PRL, and T
      were studied, and samples were collected at 10-min intervals for 360 min to
      permit cluster analysis of pulsatile release patterns. LH increased significantly
      within 30 min after nalmefene, and remained significantly above baseline levels
      for 50 to 60 min (p < 0.05). Testosterone increased significantly within 70 to 80
      min after nalmefene, and remained significantly above baseline for 60 min (p <
      0.05). Although nalmefene antagonizes opioid agonists for 6-8 h, inhibitory
      feedback by testosterone appeared to limit the duration of its antagonism of
      endogenous opioid inhibition of LHRH and stimulation of LH. Nalmefene did not
      change LH or PRL pulse frequency or amplitude significantly in comparison to
      placebo administration.

PMID- 10880680
TI  - Simultaneous monitoring of conditioned place preference and locomotor
      sensitization following repeated administration of cocaine and methamphetamine.
AB  - The paradigm of conditioned place preference has been widely used to demonstrate
      the rewarding properties of psychomotor stimulants. Such drugs also stimulate
      locomotor activity. Repeated administration of low doses of psychomotor
      stimulants causes progressive increases in the locomotor stimulating effect, a
      phenomenon termed behavioral sensitization. Using a new activity monitor (SCANET
      MV-10LD) that simultaneously measures the amount of time spent and the distance
      traveled in each side of a two-compartment chamber, the present study assessed
      place preference conditioning and locomotor sensitization following repeated
      administration of cocaine or methamphetamine (MAP) in mice. We examined the
      effect of environmental factors on these activities using two different types of
      chamber: one having a single cue, and the other having dual cues for the
      discrimination of compartments. In both types of chamber, cocaine (5-20 mg/kg)
      and MAP (1-2 mg/kg) similarly produced conditioned place preference. However,
      repeated cocaine administration caused the development of locomotor sensitization
      only in the single-cue chamber. On the other hand, repeated administration of MAP
      resulted in the development of sensitization in both types of chamber. The
      findings indicate that environmental factors differentially affect the
      development of locomotor sensitization, but not place preference conditioning,
      following repeated administration of cocaine or methamphetamine. The advantages
      of this new system will be discussed.

PMID- 10880681
TI  - Behavioral activating effects of adrafinil in aged canines.
AB  - Adrafinil, a vigilance enhancing pharmaceutical, was administered to aged dogs
      for 14 consecutive days at doses of 10, 20, 30, or 40 mg/kg using a crossover
      design. The effects on spontaneous behavior in a 10-min canine open-field test
      were systematically recorded every fourth day, starting with day 1 of treatment.
      The open field tests were given 2 or 10 h following oral administration of
      capsules containing either adrafinil or lactose, the placebo control. Adrafinil
      caused an increase in locomotor activity at the three highest doses at both the 2
      and 10-h intervals and during both the first (days 1 and 5) and second treatment
      week (days 9 and 13). Adrafinil also caused a transient increase in directed
      sniffing. At the highest dose level, adrafinil caused a decrease in urination
      frequency. The increased locomotion was generally unaccompanied by stereotypical
      behavior in the test session. There was some variability; a subpopulation of
      animals showed either no effect, or decreased locomotion. The individual
      differences were correlated with changes in serum levels of adrafinil 10 h
      following treatment.

PMID- 10880682
TI  - Oral administration of adrafinil improves discrimination learning in aged beagle
      dogs.
AB  - Aged beagle dogs were trained on either a size or intensity discrimination task 2
      h following treatment with either 20 mg/kg of adrafinil or a placebo control.
      Training continued until the dogs reached a predetermined criterion level of
      performance, or failed to acquire the task after 40 sessions. The treatments and
      tasks were then reversed, with both the test order and treatment order
      counterbalanced. Thus, half of the animals were first tested on the intensity
      discrimination, and half of these were first tested under adrafinil. Treatment
      with adrafinil produced significant improvement in learning, as indicated by a
      decrease in both errors and trials to criterion. An effect of adrafinil on
      motivation may partially account for these findings; however, adrafinil did not
      significantly affect response latency. Adrafinil is believed to serve as an alpha
      1 adrenoceptor agonist. The improved learning may also result from enhancement of
      vigilance due to facilitation of noradrenergic transmission in the central
      nervous system.

PMID- 10880683
TI  - Microinjections of dopaminergic agents in the nucleus accumbens affect ethanol
      consumption but not palatability.
AB  - It was determined whether ethanol palatability in rats could be changed by
      manipulating the reinforcement experienced during limited access consumption.
      During the first 3 days of the experiment, initial taste reactivity (TR) testing
      to distilled water (1 day) and 10% alcohol (2 days) was performed. Following the
      establishment of baseline TR, separate groups of animals received bilateral
      microinjections (0.5 microl/side) into the nucleus accumbens of either the
      nonspecific dopamine agonist d-amphetamine sulfate (20 microg, n = 10), the D(2)
      antagonist raclopride (1.0 microg, n = 8), or physiological saline (n = 5). The
      injections occurred at the same time each day for 5 consecutive days. Five
      minutes after the microinjection, the fluid-deprived rats were given 30-min
      access to 10% ethanol. Over the 3 days following drug administration, TR to
      distilled water and 10% alcohol was repeated. After this, the rats were once
      again given 30 min of access to 10% ethanol for 5 consecutive days, but without
      drug microinjection prior to alcohol access. A final TR exposure (the same as the
      others) was performed over the final 3 days of the study. Both raclopride and d
      amphetamine administration produced reductions in ethanol consumption (in
      comparison to saline treatment). However, treatment with d-amphetamine and
      raclopride during ethanol consumption did not cause significant, conditioned
      changes in palatability as measured by the taste reactivity procedure. These
      results suggest that dopamine plays a role in the motivation to consume ethanol
      but this neurotransmitter is not involved in evaluating its incentive value.

PMID- 10880684
TI  - Effects of cocaine and morphine under mixed-ratio schedules of food delivery:
      support for a behavioral momentum analysis.
AB  - Previous studies have shown that ratio size influenced the development of
      tolerance under simple and multiple schedules, but not under progressive-ratio
      (PR) schedules. PR schedules share certain features with mixed-ratio (MR)
      schedules, and pilot data suggested that ratio size fails to modulate tolerance
      to cocaine or morphine under MR schedules. The present study examined more
      comprehensively the pre- and postchronic effects of cocaine and (in separate
      birds) morphine under MR schedules with fixed-ratio (FR) 5 and FR 95, FR 25 and
      FR 75, and FR 50 and FR 50 components. Acute doses of cocaine and morphine
      initially were given in an ascending series (beginning with 0.56 mg/kg) until
      responding was reduced to near-zero levels. Chronic (daily) dosing with a dose
      that reduced, but did not eliminate, responding then occurred until response
      rates stabilized. Finally, postchronic dose-response determinations were
      conducted. Both cocaine and morphine reduced response rates at all FR values.
      Tolerance was consistently observed to the effects of morphine, but not to those
      of cocaine. With both drugs the degree of tolerance observed did not vary as a
      function of FR value. These findings, like those obtained under PR schedules,
      indicate that ratio size does not always modulate drug tolerance. A behavioral
      momentum analysis of drug action appears to account for whether or not ratio size
      modulates tolerance, and such an analysis is provided.

PMID- 10880685
TI  - A rodent model of cocaine abstinence syndrome.
AB  - This study introduces a rat model of cocaine abstinence syndrome based on
      quantitation of spontaneously emitted behaviors following termination of
      continuous drug exposure (analogous to established methods of assessing morphine
      and nicotine abstinence). Groups of eight male S-D rats were infused SC for 7
      days via an osmotic minipump with saline alone or with 40 or 60 mg/kg/day cocaine
      HCl. Pumps were removed and rats were observed at 12, 24, 36, and 48 h
      postremoval. Each 15-min observation employed a checklist of abstinence signs
      including ptosis, chews, teeth chatters, gasps, writhes, seminal ejaculations,
      head shakes, and tremors. The high infusion rate group displayed significantly
      more signs than the low infusion rate group, which in turn, displayed
      significantly more signs than the saline group. Cocaine injection significantly
      reduced signs by 83.3%, while saline injection reduced them by only 4.9%. In
      another experiment, rats infused with 60 mg/kg/day showed significantly more
      signs 36 h postinfusion than before infusion, during infusion and 84 h
      postinfusion. Finally, 6.5 days of infusion resulted in significantly more
      abstinence signs than did 1.5 days of infusion. This rapid and simple model
      quantitated cocaine abstinence syndrome in a manner that was cocaine-reversible
      and related to the rate and duration of drug infusion.

PMID- 10880686
TI  - Ethopharmacology of the antidepressant effect of clonazepam in diabetic rats.
AB  - Diabetes-associated depression may occur due to changes in the quality of life
      imposed by treatment, or may be a consequence of the biochemical changes
      accompanying the disease. It was our objective to evaluate the behaviors of
      diabetic rats through an animal model of depression, and determine if a positive
      GABA modulator agent, clonazepam, is an effective antidepressant. Wistar male
      rats were submitted to the forced-swimming test after 26 days of the induction of
      diabetes with streptozotocin (60 mg/kg). Test and retest days analyzed with an
      ethological approach. Clonazepam (control, 0.25, 0. 5, and 1.0 mg/kg) was
      administered IP 24, 5, and 1 h before the retest. Diabetic rats presented longer
      immobility duration during test and retest of forced swimming. Diabetic rats
      dived significantly less during the test. Clonazepam 0.25 and 0.5 mg/kg decreased
      immobility of diabetic rats with no consequences on the behaviors of nondiabetic
      rats. These results demonstrate that diabetic rats present more intense
      depressive-like behavior, such as immobility and lack of interest in exploring
      the environment, when exposed to the forced-swimming test. It is possible that
      decreased GABA function is involved in depression associated with diabetes,
      because a benzodiazepine partially counteracts these changes without modifying
      blood glucose and glycogen parameters.

PMID- 10880687
TI  - Multiple ejaculations and chronic fluoxetine: effects on male rat copulatory
      behavior.
AB  - Male rats were treated with fluoxetine (FLX) or vehicle daily for 14 days and
      copulatory behavior tested on day 15. Rats were either mated to three
      ejaculations or to sexual exhaustion. Both standard measures and the mount bout
      analysis were used to evaluate the effects of the chronic FLX on male rat
      copulatory behavior. Only 56.25% of the animals treated with FLX achieved three
      ejaculations. FLX inhibited the consumatory aspect of male sexual behavior,
      especially the ability to achieve three ejaculations, but there was no effect on
      the propensity of the male to pursue the female. These differences were observed
      for the first three ejaculations. Analysis of the last three ejaculations in
      those animals that mated to exhaustion did not reveal an effect of FLX. The
      behavioral pattern of FLX-treated animals during the first three ejaculations
      resembled that observed during the last three ejaculatory series in the vehicle
      treated animals that mated to exhaustion. The results are discussed in terms of
      the serotonergic effects on male rat sexual behavior.

PMID- 10880688
TI  - Long-term voluntary access to running wheels decreases kappa-opioid
      antinociception.
AB  - Previous research has demonstrated that voluntary exercise is associated with a
      reduction in mu-opioid-induced antinociception. To determine if the effects of
      voluntary exercise on opioid-induced antinociception were limited to drugs that
      affect the mu opioid receptor or were more general, the analgesic effects of the
      kappa opioid agonist U50,488H were compared in active and sedentary rats. Eight
      adult male Long-Evans rats were housed in standard hanging cages and eight in
      cages with attached running wheels for 20 days prior to antinociceptive testing.
      Pain thresholds were determined using a tail-flick procedure, and antinociception
      was expressed as percent maximal possible effect (%MPE). In the first study,
      U50,488H was administered in a cumulative dosing procedure (5.0, 10.0, 20.0
      mg/kg). Tail-flick latencies were measured immediately prior to and 30 min
      following each injection. In the second study, the time course of U50,488H
      effects was examined in animals from the first experiment. Tail-flick latencies
      were measured immediately prior to and 30, 60, and 90 min following 10.0 mg/kg
      U50,488H. In the first study, U50,488H produced significant antinociception in
      both groups of rats. However, antinociceptive responses were significantly
      reduced for rats given access to running wheels relative to inactive rats. In the
      second study, antinociceptive responses to U50,488H continued for 90 min. Again,
      antinociceptive responses were lower for rats given access to running wheels
      relative to inactive rats. These results indicate that long-term voluntary
      exercise decreases the antinociceptive properties of the kappa agonist U50,488H,
      as well as the mu agonist morphine.

PMID- 10880689
TI  - The effect of nimodipine on opioid antagonist-induced upregulation and
      supersensitivity.
AB  - Regulation of calcium flux has been suggested to play a role in acute and chronic
      effects of opioids. Previous studies have shown calcium channel blockers can
      inhibit opioid agonist-induced downregulation of mu-opioid receptors and may
      reduce the magnitude of tolerance. In the present study, we determined if calcium
      channel blockade would affect increases in opioid receptor density and functional
      supersensitivity produced by chronic opioid antagonist treatment in the mouse.
      Mice were implanted subcutaneously with a 15-mg naltrexone (NTX) or placebo
      pellet. Mice also were implanted with an osmotic minipump that infused nimodipine
      (100 microg/kg/day) or a second placebo pellet. This protocol yielded four
      groups: nimodipine-NTX; nimodipine-placebo; placebo-NTX; placebo-placebo. On the
      seventh day, pumps and pellets were removed. Twenty-four hours later, a morphine
      dose-response study was conducted (tail flick); or mice were sacrificed and
      saturation binding studies ([3H]DAMGO) were performed in whole brain. NTX
      treatment significantly increased the analgesic potency of morphine by
      approximately 60%. Nimodipine increased the potency of morphine by approximately
      50%. For mice treated with both nimodipine and NTX, there was an additive effect
      on morphine potency ( approximately 120% increase). In binding studies, NTX
      increased the density of mu-opioid receptors similarly ( approximately 60-70%) in
      the presence and absence of nimodipine treatment, with no change in affinity. No
      effect of chronic nimodipine alone on mu-opioid receptor binding was observed.
      These data indicate that NTX-induced upregulation and supersensitivity are
      independent of calcium channel blockade by nimodipine. These results contrast
      with those from tolerance and downregulation studies, and confirm suggestions
      that different substrates mediate chronic opioid agonist and antagonist-induced
      effects in vivo. Finally, in a separate study, morphine potency was unaffected by
      acute nimodiopine (100 microg/kg; SC), suggesting that prolonged exposure to this
      calcium channel blocker is required to increase morphine potency.

PMID- 10880690
TI  - Effects of low dosages of apomorphine on maternal responsiveness in lactating
      rats.
AB  - Lactating rats (day 7 +/- 1 postpartum) were observed during a 1-h reunion with
      their pups 4 h after separation from them and 10 min after subcutaneous injection
      of saline (SAL; 0.1 ml) or low dosages of the dopamine agonist, apomorphine (APO;
      0.1 or 0.25 mg/kg). Although APO did not affect latency to sniff pups or retrieve
      the first pup, there were dosage-dependent delays in onset of licking and nursing
      pups, and decreases in retrieval and grouping of pups, nursing duration, and
      litter weight gain. The alterations in maternal responsiveness among APO-treated
      dams were related to increased carrying and mouthing of pups and markedly
      increased sniffing of pups, bedding, and cage. Duration of time spent licking
      pups, exploring, and self-grooming did not differ between groups. Thus, certain
      APO-induced stereotypic behaviors interfered with the normal sequence of maternal
      behavior by exaggerating some components and delaying others. These results are
      relevant to disturbances in maternal behavior caused by hyperreactivity or by
      other drugs that increase dopaminergic activity, such as cocaine.

PMID- 10880691
TI  - Precipitated and spontaneous withdrawal following administration of lorazepam but
      not zolpidem.
AB  - Radiotelemetry was utilized to compare zolpidem and lorazepam tolerance and
      withdrawal in rats. Locomotor activity, electromyographic activity (EMG), and
      body temperatures were used to assess the acute drug effects, and as measures of
      tolerance and withdrawal. Lorazepam, zolpidem, or vehicle was administered for 12
      days, and data were recorded daily, immediately, after treatment. Data were also
      recorded immediately after flumazenil (25 mg/kg, IP) precipitated withdrawal and
      during 4 days of spontaneous withdrawal. Complete tolerance to the acute effects
      of lorazepam administration developed within 7 days of treatment and both
      flumazenil-precipitated and spontaneous withdrawal were observed. In contrast,
      there was no tolerance to the sedative actions of zolpidem administration after
      12 days, but complete tolerance to the hypothermic and muscle relaxant effects
      was apparent after 8 days of treatment. Despite the presence of tolerance, no
      evidence of either spontaneous or flumazenil-induced withdrawal was recorded in
      these rats. In conclusion, this model suggests that as a sedative zolpidem has
      significant advantages over the classic benzodiazepines.

PMID- 10880692
TI  - Mice lacking the long splice variant of the gamma 2 subunit of the GABA(A)
      receptor are more sensitive to benzodiazepines.
AB  - The gamma 2 subunit is required for benzodiazepine modulation of the GABA(A)
      receptor. Alternate splicing of precursor GABA(A) gamma 2 mRNA results in two
      splice variants, a short (gamma 2S) and a long (gamma 2L) variant. We
      investigated the roles of these splice variants in benzodiazepine pharmacology
      using mice lacking genes for the gamma 2L splice variant. Sleep time responses to
      midazolam and zolpidem were 20 and 18% greater, respectively, in null allele mice
      compared with wild-type mice, while responses to nonbenzodiazepine agents such as
      etomidate and pentobarbital were unchanged. Although the GABA(A) receptor number
      was not altered in null allele mice, there was a corresponding increase in
      affinity of brain membranes for benzodiazepine agonists (midazolam, diazepam, and
      zolpidem), while affinity for benzodiazepine inverse agonists (beta CCM and Ro15
      4513) was decreased. These changes were not observed in inbred mice of the
      parental strains (C57BL/6J and 129/SvJ) used to create the genetically altered
      mice, indicating that differences between gamma 2L null allele and wild-type mice
      were unlikely to be simply due to cosegregation of linked alleles. Absence of the
      gamma 2L splice variant increases the affinity of receptors for benzodiazepine
      agonists, and is associated with a modest increase in behavioral sensitivity to
      benzodiazepine agonists. Lack of the gamma 2L subunits may shift the GABA(A)
      receptor from an inverse agonist-preferring toward an agonist-preferring
      configuration.

PMID- 10880693
TI  - The importance of acclimation in acoustic startle amplitude and pre-pulse
      inhibition testing of male and female rats.
AB  - The acoustic startle reflex (ASR) and pre-pulse inhibition (PPI) of the ASR are
      used extensively to index drug effects in rodents. Important methodological
      issues exist, however, with regard to the specific procedures and equipment used.
      In particular, the effects of acclimation to the startle procedure on response
      stability and the effects of testing animals in groups vs. individually have not
      been examined but are relevant to data interpretation. The present experiment
      measured acoustic startle responses with and without a pre-pulse of 25 adult
      Sprague-Dawley rats (12 male, 13 female) tested individually and in same-sex
      groups at four time points. Individual testing increased startle responses and
      PPI of males at time 1 and altered PPI of females at times 1, 2, and 3 compared
      with group testing. Responses were indistinguishable in the two testing
      environments at time 4. Results indicate that testing environment may affect
      responses when subjects have not been acclimated to the testing situation and
      that there are sex differences in these effects. Because responses stabilized by
      the fourth testing point, repeated testing of subjects particularly females, may
      be an important methodological inclusion when evaluating effects of drugs and
      other manipulations on ASR and PPI.

PMID- 10880694
TI  - Factors elevating cAMP attenuate the effects of 8-OH-DPAT on lordosis behavior.
AB  - The effects of a soluble derivative of forskolin and of two membrane-permeable
      analogs of cAMP, dibutyryl cAMP, and 8-bromo-cAMP, on the ability of a serotonin
      (5-HT)(1A) receptor agonist to inhibit lordosis behavior were examined. Sexually
      receptive, proestrous rats received a bilateral infusion into the ventromedial
      nucleus of the hypothalamus (VMN) with 68 ng of the forskolin derivative 1, 1.5,
      2, or 2.5 h prior to infusion with 200 ng of the 5-HT(1A) receptor agonist, (+/-)
      8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Proestrous rats and
      ovariectomized rats, hormonally primed with 25 microg estradiol benzoate and 500
      microg progesterone, were coinfused with 200 ng 8-OH-DPAT and either 50 microg
      dibutyryl cAMP or 5 microg 8-bromo-cAMP. In proestrous rats, prior infusion with
      the forskolin derivative reduced the effects of the 5-HT(1A) receptor agonist on
      lordosis behavior. The best protection occurred at 2 h; by 2.5 h after the
      preinfusion, any protective effect had disappeared. Coinfusion with either
      dibutyryl-cAMP or 8-bromo-cAMP reduced the effects of 8-OH-DPAT in proestrous
      rats. In hormone-primed, ovariectomized rats, dibutyryl cAMP offered significant
      protection against the effects of 8-OH-DPAT, but there was no protection with 8
      bromo-cAMP. These findings are consistent with the speculation that 8-OH-DPAT's
      inhibition of lordosis behavior results, in part, from an inhibition of adenylyl
      cyclase, resulting from agonist activation of 5-HT(1A) receptors in the VMN. The
      findings are also consistent with our earlier observations for differences
      between proestrous rats and hormone-primed, ovariectomized rats in their response
      to 5-HT receptor-active compounds.

PMID- 10880695
TI  - Inhibitory effect of buspirone and diazepam, but not of 8-OH-DPAT, on maternal
      behavior and aggression.
AB  - The action of diazepam (0.0, 1.0, and 2.0 mg/kg) and the serotonergic compounds
      buspirone (0.0, 2.5, and 5.0 mg/kg) and 8-OH-DPAT (0.0, 0.1, and 1.0 mg/kg) on
      maternal behavior and aggression were studied. An activity test was made after
      these treatments to control for unspecific actions due to motor impairment.
      Diazepam and buspirone dose-dependently inhibited the expression of maternal
      aggression and the active components of maternal behavior such as retrieving and
      nest building. 8-OH-DPAT did not affect these behaviors. 8-OH-DPAT (1.0 mg/kg)
      provoked the serotonergic syndrome and hypothermia; however, ovariectomized
      animals showed more signs of the syndrome and a decrease in body temperature
      after 8-OH-DPAT than lactating rats. Buspirone, but not the other anxiolytics,
      reduced motor activity. The role of drugs acting at the serotonergic,
      dopaminergic, and GABA-benzodiazepine systems in the control of maternal behavior
      and aggression is discussed.

PMID- 10880696
TI  - Cocaine intake by rats correlates with cocaine-induced dopamine changes in the
      nucleus accumbens shell.
AB  - Extracellular dopamine levels were determined by microdialysis in the core and
      shell of the nucleus accumbens and the frontal cortex of rats before and after an
      injection of cocaine (20 mg/kg, IP). After removal of the probes, these same
      animals were then tested for their voluntary intake of cocaine using the two
      bottle, free-choice paradigm. Baseline dopamine levels and their responses to an
      injection of cocaine differed among the three brain areas. No significant
      correlations were found between baseline dopamine levels in any of the three
      brain regions and the voluntary cocaine consumption. A significant negative
      correlation was found between cocaine-induced increases in extracellular dopamine
      in the shell of the nucleus accumbens and the voluntary intake of cocaine (r = 
      0.73, p < 0.01). No such correlations were observed in the accumbens core region
      or the frontal cortex. These results provide further evidence of the role of the
      accumbal shell region in cocaine preference, and indicate that cocaine-induced
      increases in dopamine levels play a role in oral cocaine self-administration or
      preference. In addition, this relatively novel approach in using the same animals
      for both cocaine induced neurotransmitter responses and cocaine preference
      studies can also be applied for the study of other neurotransmitters and drugs of
      abuse.

PMID- 10880697
TI  - Behavioral effects Of 8-OH-DPAT in chronically stressed male and female rats.
AB  - The present study tested the hypothesis that chronic stress desensitizes
      serotonergic 5-HT(1A) receptors and alters behavioral changes following 5-HT(1A)
      agonist administration. Eating, acoustic startle response (ASR), and locomotor
      activity were measured in stressed and nonstressed male and female rats after 8
      OH-DPAT administration. Stressed rats were paired and stressed by around-the
      clock intermittent foot shock. Controllable stress (CS) rats could
      avoid/terminate shock for themselves and their yoked partners by pulling a
      ceiling chain, whereas their partners, the uncontrollable stress (UCS) rats,
      could not. Rats earned their entire daily ration of food by pressing a lever. In
      previous experiments, this paradigm was stressful, but not debilitating and rats
      continued to eat, groom, sleep, and avoid/escape greater than 99% of shock
      trials. Locomotor activity and ASR were measured in the present study after
      saline and 8-OH-DPAT administration (0.25 mg/kg, IP) before, 24 h, and 72 h after
      shock onset. 8-OH-DPAT only decreased food intake significantly in male and
      female rats after the first administration. Stress decreased food intake in both
      the CS and UCS rats, with UCS rats eating the least. However, the effects of
      stress and 8-OH-DPAT were not additive. 8-OH-DPAT significantly increased peak
      startle amplitude at 100 and 120 dB, and decreased latency to peak startle
      amplitude at 100 dB in male and female rats. In contrast, 8-OH-DPAT did not alter
      percent prepulse inhibition (%PPI) at 100 dB, but significantly decreased %PPI in
      males but not females at 120 dB. Stress did not have a consistent effect on ASR,
      but reduced %PPI in males, but not females. Neither stress nor 8-OH-DPAT
      significantly altered locomotor activity. Although the results do not show an
      increased sensitivity to 8-OH-DPAT in stressed rats, the unexpectedly weak
      effects of 8-OH-DPAT alone on the behavioral measures chosen limits the
      conclusions that can be drawn.

PMID- 10880698
TI  - Potentiation of ethanol-induced loss of the righting reflex by ascorbic acid in
      mice: interaction with dopamine antagonists.
AB  - The present investigation was carried out to determine the effect of ascorbic
      acid on ethanol-induced loss of the righting reflex (LORR) and the interactions
      between ascorbic acid and dopamine receptor antagonists in affecting this action
      of ethanol in mice. To test the effect of each drug on ethanol-induced LORR,
      ascorbic acid (31.25, 62.5, 125, 250, 500, 1000 mg/kg intraperitoneally [IP]) and
      dopamine receptor antagonists (haloperidol 0.5, 1.0 mg/kg; L-sulpiride 20, 40, 80
      mg/kg; clozapine 0.625, 1.25, 2.5 mg/kg; SCH 23390 0.5, 1.0, 2.0 mg/kg
      subcutaneously [SC]) were administered, respectively, 30 min before ethanol (4.0
      g/kg IP) administration. Ascorbic acid, at the dose of 1000 mg/kg, significantly
      potentiated ethanol-induced LORR in mice. Dopamine D(2) antagonists haloperidol
      (0.5, 1.0 mg/kg SC), and L-sulpiride (80 mg/kg SC) also significantly prolonged
      the duration of LORR induced by ethanol. Clozapine and SCH 23390, at the doses
      used, did not affect ethanol-induced LORR. In the interaction study, the
      synergistic effect of ascorbic acid (1000 mg/kg IP) on ethanol-induced LORR was
      significantly enhanced by dopamine D(2) antagonists haloperidol, L-sulpiride, and
      clozapine, and the highest dose of dopamine D(1) antagonist SCH 23390. These
      results suggest that ascorbic acid may potentiate ethanol-induced LORR partially
      via a mechanism mainly linked to blockade of dopamine D(2) receptors.

PMID- 10880699
TI  - Opiate withdrawal in the fetal rat: a behavioral profile.
AB  - Offspring of women exposed to opiate drugs such as heroin and methadone during
      pregnancy have a high incidence of morbidity and mortality. Infants also show
      opiate withdrawal. In this study, we examined the behavioral effects of
      precipitated withdrawal in morphine-dependent fetal rats at gestational day (GD)
      20. The dam was implanted on GD 14 with a pellet containing 75.0 mg of morphine.
      On GD 20, the dam underwent chemoyelotomy at L1/L2. The uterine horns were
      externalized and four subject fetuses were selected for behavioral observation,
      two from each uterine horn. The fetus was then injected subcutaneously with
      either saline or naltrexone (1.0 mg/kg) and the behaviors of the fetus recorded
      every 15 sec for 20 min. The results show that naltrexone injected fetuses that
      had been chronically exposed to morphine demonstrated increased limb and mouth
      movements, face wiping, and body curls, and spent less time quiet as compared
      with control fetuses. These results indicate that a morphine withdrawal-like
      syndrome occurs in the fetal rat.

PMID- 10880700
TI  - Pentylenetetrazol-kindling modulates stimulated dopamine release in the nucleus
      accumbens of rats.
AB  - Kindling-induced activation of dopaminergic neurones in the nucleus accumbens in
      pentylenetetrazol (PTZ)-kindled rats was studied using microdialysis. Dopamine
      (DA) release after PTZ challenge was measured: (1) two weeks and (2) ten weeks
      after kindling completion and (3) two weeks after a kindling procedure with
      diazepam (DZP) treatment. In (1) a significant increase in DA concentration was
      found after PTZ challenge and this increase was still evident 10 weeks after
      kindling completion (2). Coadministration of DZP in the course of kindling
      development inhibited the increase in sensitivity of the accumbens dopaminergic
      system (3).

PMID- 10880701
TI  - Food intake after diazepam, morphine or muscimol: microinjections In the nucleus
      accumbens shell.
AB  - This study examined the effect on food intake of bilateral microinfusions of the
      benzodiazepine agents, diazepam and midazolam, the opioid agonist, morphine, and
      the GABA(A) agonist, muscimol into the shell of the nucleus accumbens in rats.
      Both muscimol (at 0.075 microg, combined bilateral dose) and morphine (1.0
      microg) in the nucleus accumbens shell increased feeding as expected. However, it
      was clear that diazepam (2.5, 5.0, 25, 50 microg) and midazolam (7.5 microg) both
      failed to enhance feeding even at doses that are effective when microinjected in
      the brain stem. We conclude that opioid and GABA(A) agents promote feeding
      behavior by acting on receptors in the nucleus accumbens shell, but that
      benzodiazepines probably act elsewhere in the brain to increase food intake.

PMID- 10880702
TI  - Importance of environmental context in the development of amphetamine- or
      apomorphine-induced stereotyped behavior after single and multiple doses.
AB  - The present study was designed to determine whether single and repeated
      pretreatment regimens with amphetamine or apomorphine differ in the context
      dependency of sensitization of stereotyped behavior. Male CF-1 mice that were
      pretreated with a single high dose of amphetamine (14 mg/kg intraperitoneally
      [IP]) or apomorphine (40 mg/kg subcutaneously [SC]) only became sensitized to a
      lower test dose of amphetamine (7 mg/kg IP) or apomorphine (3 mg/kg SC) when
      placed in an environment that was the same as the pretreatment environment.
      However, animals pretreated with 3 high doses (24-h apart) of amphetamine (14
      mg/kg IP) or apomorphine (40 mg/kg SC) did demonstrate sensitization to a lower
      test dose of amphetamine (7 mg/kg IP) or apomorphine (3 mg/kg SC) when placed in
      an environment that was different from the pretreatment environment. Context
      dependent sensitization, but not context-independent sensitization, was
      extinguished by pairing the test environment with saline injections instead of
      drug injections. In addition, it was determined that neither sensitization model
      could be related to pharmacokinetic factors. Therefore, the results indicate that
      repeated exposure to amphetamine or apomorphine overcomes the context-dependent
      component of sensitization of amphetamine- or apomorphine-induced stereotyped
      behavior.

PMID- 10880703
TI  - Central 5-HT(4) receptors and drinking behavior.
AB  - The aim of the present study was to investigate the effect of acute third
      ventricle injections of two different 5-HT(4) receptor antagonists, GR 113808 and
      SB 204070, on water intake in different situations. Injections of 80 nmol/rat of
      both GR 113808 and SB 204070 were unable to modify water intake in normohydrated
      rats. Pretreatment with GR 113808 (40 and 80 nmol/rat) and SB 204070 (80 and 160
      nmol/rat) blunted water intake after third ventricle injections of angiotensin II
      (9.6 pmol/rat) compared to saline-pretreated controls. Pretreatment with 80
      nmol/rat of both antagonists potentiated drinking induced by third ventricle
      injections of carbachol (11.0 nmol/rat) compared to saline-pretreated control. In
      all doses employed, none of the compounds was able to modify water intake in
      dehydrated rats. A separate control test using one-bottle taste aversion paradigm
      indicated that the reduction in water intake observed in some of the present
      experiments could not be attributed to a drug-induced malaise. It is suggested
      that central 5-HT(4) receptors exert a dualistic role on the control of water
      intake potentiating angiotensin II-induced drinking and inhibiting thirst induced
      by central cholinergic activation

PMID- 10880704
TI  - Cocaine affects progesterone plasma levels in female rats.
AB  - Female Fischer rats injected with cocaine in a "binge" pattern (15 mg/kg, IP,
      three times a day, at 1-h intervals) for 1 day had significantly higher levels of
      progesterone than saline-treated controls (p < 0.001). When analyzed by the stage
      of the estrous cycle, animals in proestrus showed significantly higher cocaine
      induced progesterone plasma levels than those in other stages of the cycle (p <
      0.01). Progesterone plasma levels were also increased after a single dose of
      cocaine (15 mg/kg). However, 3 h postinjection progesterone plasma levels had
      returned to normal. Thus, cocaine modulation of progesterone plasma levels
      appears to be an acute effect. In ovariectomized rats pretreated with estrogen,
      progesterone, or estrogen + progesterone, no significant differences were
      observed in progesterone plasma levels after acute "binge" pattern cocaine
      administration. Thus, acute cocaine induced increases in progesterone plasma
      levels in intact female rats are probably due to an increase in secretion rates
      of progesterone rather than an acceleration of its biotransformation. Due to the
      profound effects of progesterone in the modulation of CNS plasticity, the
      modulation of progesterone plasma level by cocaine may have implications for
      reproductive processes and neuronal functions of women. Moreover, cocaine may
      affect the progesterone levels in women utilizing progesterone-based
      contraception or steroid replacement treatment after menopause.

PMID- 10880705
TI  - A comparison of the reinforcing efficacy of alcohol in alcohol-preferring (P) and
      alcohol-nonpreferring (NP) rats.
AB  - A key feature of the selective breeding program that produced alcohol-preferring
      (P) and alcohol-nonpreferring (NP) rats is that the alcohol was mixed with water.
      However, humans typically drink sweetened or palatably flavored alcohol. The
      experiments in this study tested whether the differences in P and NP rats
      generalize to sweetened alcohol. In Experiment 1, P rats drank more alcohol than
      NP rats when the vehicle was water, but NP rats drank about as much alcohol as P
      rats (1.1 to 1.3 g/kg/30 min) when the vehicle was a saccharin solution.
      Experiment 2 tested whether P rats were more susceptible to the rewarding
      properties of sweetened alcohol than were NP rats. The criterion for reward
      strength was the degree to which alcohol-reinforced lever pressing persisted,
      despite increases in the schedule requirements for the alcohol reward. In
      baseline, lever presses were reinforced with sweetened alcohol and an isocaloric
      Polycose solution according to two, concurrent, variable-interval 5-s schedules.
      In subsequent conditions, the interval schedule for alcohol was increased, and
      then, after a return to baseline, the interval schedule for Polycose was
      increased. By the criterion of resistance to change, alcohol was a stronger
      reinforcer than was Polycose, and alcohol was a stronger reinforcer in NP rats
      than in P rats.

PMID- 10880706
TI  - Somatization in primary care: it's time for parity.

PMID- 10880707
TI  - Unexplained symptoms in primary care: perspectives of doctors and patients.
AB  - This study evaluated unexplained symptoms in primary care from the perspective of
      both patients and physicians. The data were obtained from two 1998 statewide
      surveys, one targeting Medicaid patients and the other all primary care
      physicians in the state. There were 439 patients who responded (45% response
      rate) and 280 primary care physicians who responded (33% response rate). Half of
      the patients and half of the physicians were in non-metropolitan counties. Half
      of the patients reported unexplained symptom usually or always, and 75% of whom
      sought help for these symptoms. Fifty-two percent of these patients believed
      their physician was very concerned about their unexplained symptoms. Eighty
      percent of them rated their physician as providing the best possible care
      compared to only 49% of patients whose physician did not care about their
      unexplained symptoms (P=.001). Among the physicians, only 14% reported very good
      or excellent satisfaction with managing unexplained symptoms as compared to 44%
      who claimed similar satisfaction in managing psychological problems. Physicians
      who saw themselves as more effective in dealing with somatoform symptoms were
      more likely to be in solo practice (P<.005), or in the same location for at least
      five years (P=.04). Residence in a nonmetropolitan county did not affect patient
      reporting of symptoms, patient perception of physician concern about symptoms, or
      physician satisfaction in managing these symptoms. These results indicate the
      prevalence and importance of unexplained symptoms in the Medicaid population and
      the comfort of physicians in managing these symptoms. There is an unmet need
      among primary care physicians to learn how to manage patients with unexplained
      symptoms.

PMID- 10880708
TI  - Recovery from depression, work productivity, and health care costs among primary
      care patients.
AB  - We describe a secondary analysis of data from a randomized trial conducted at
      seven primary care clinics of a Seattle area HMO. Adults with major depression
      (n=290) beginning antidepressant treatment completed structured interviews at
      baseline, 1, 3, 6, 9, 12, 18, and 24 months. Interviews examined clinical
      outcomes (Hamilton Depression Rating Scale and depression module of the
      Structured Clinical Interview for DSM-IIIR), employment status, and work days
      missed due to illness. Medical comorbidity was assessed using computerized
      pharmacy data, and medical costs were assessed using the HMO's computerized
      accounting data. Using data from the 12-month assessment, patients were
      classified as remitted (41%), improved but not remitted (47%), and persistently
      depressed (12%). After adjustment for depression severity and medical comorbidity
      at baseline, patients with greater clinical improvement were more likely to
      maintain paid employment (P=.007) and reported fewer days missed from work due to
      illness (P<.001). Patients with better 12-month clinical outcomes had marginally
      lower health care costs during the second year of follow-up (P=.06). We conclude
      that recovery from depression is associated with significant reductions in work
      disability and possible reductions in health care costs. Although observational
      data cannot definitively prove any causal relationships, these longitudinal
      results strengthen previous findings regarding the economic burden of depression
      on employers and health insurers.

PMID- 10880709
TI  - Primary care patients' opinions regarding the importance of various aspects of
      care for depression.
AB  - The objectives of this study were to 1) ascertain the importance of various
      aspects of depression care from the patient's perspective and 2) select items and
      scales for inclusion in a new instrument to measure primary care patients'
      attitudes toward and ratings of depression care. We used a cross-sectional survey
      at a university-based urban primary care clinic; the subjects were adult patients
      being recruited for a study of minor depression. To help prioritize attitudinal
      domains, including 126 items identified previously in focus groups, we asked
      patients to rate the importance of each aspect of depression care on a five-point
      scale. Items were ranked according to mean scores and the percentage of patients
      ranking the items as extremely important. The items were selected for inclusion
      in an instrument to measure patients' attitudes toward depression care based on
      their importance ratings. We performed reliability and validity testing of scales
      comprising the 30 most important items and a shortened version that includes 16
      items. The sample included 76 patients (mean age 34.8 years; mean CES-D score,
      22.2; 72% women; 36% African-American; 32% college graduates). Forty-six percent
      had visited a mental health professional in the past. The top 30 items for the
      overall sample came from the following domains: 1) health care providers'
      interpersonal skills, 2) primary care provider recognition of depression, 3)
      treatment effectiveness, 4) treatment problems, 5) patient understanding about
      treatment, 6) intrinsic spirituality, and 7) financial access to services. Scales
      comprising items from these domains show adequate internal consistency
      (Cronbach's alpha >0.70) as well as convergent and discriminant validity. We have
      designed a brief patient-centered instrument for measuring attitudes toward
      depression care that has evidence for internal item consistency reliability and
      discriminant validity.

PMID- 10880711
TI  - Yujiro ikemi, M.D

PMID- 10880710
TI  - Patterns of self-harm behavior among women with borderline personality
      symptomatology: psychiatric versus primary care samples.
AB  - The current study investigated differences in self-harm behavior among
      individuals with borderline personality symptomatology from two different
      clinical settings. Participants were women, between the ages of 18 and 45, from
      an outpatient mental health setting or a primary care setting. Each participant
      completed the Self-Harm Inventory (SHI) and the borderline personality scale of
      the Personality Diagnostic Questionnaire-Revised (PDQ-R). Using a predetermined
      cut-off for substantial borderline personality symptomatology on the SHI, group
      comparisons with chi(2) analyses indicated that "overdosed" and "hit self" were
      significantly more common in the mental health subsample whereas "abused
      laxatives" was significantly more common in the primary care subsample. Using a
      predetermined cut-off for borderline personality on the PDQ-R, chi-square
      analyses indicated that "overdosed" and "hit self" remained significantly more
      common in the mental health subsample. Despite these differences, there was
      remarkable similarity of symptoms between groups. The implications of these
      findings are discussed.

PMID- 10880712
TI  - Comparison of the internal state scale to clinician-administered scales in asthma
      patients receiving corticosteroid therapy.
AB  - Mood symptoms are reported frequently in asthma patients, particularly during
      corticosteroid therapy. This investigation compared the Internal State Scale
      (ISS), a self-report measure of symptoms of mania and depression, to the Hamilton
      Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief
      Psychiatric Rating Scale (BPRS) in a group of asthma patients (n=60 at baseline)
      before, during, and after a 1-2 week burst of prednisone. The depression and well
      being subscales of the ISS correlated well with HDRS scores. The perceived
      conflict subscale correlated with the BPRS scores. However, none of the ISS
      subscales correlated consistently and specifically with the YMRS in this
      population. Possible explanations for differences observed in bipolar versus
      asthma patients given the ISS are discussed. These data suggest the ISS may be a
      useful tool for depression symptoms and overall psychopathology in asthma
      patients and in patients receiving corticosteroid therapy. However, its ability
      may be attenuated outside of the population for which it was designed.

PMID- 10880713
TI  - Predictors of outcome in a short-term psychiatric day hospital program.
AB  - This study assessed selected chronicity, social support, and personality
      variables as predictors of outcome in a 3-week psychiatric day hospital program.
      Measured outcome included pre- and post-treatment scores on the BDI, STAI, and
      SCL-90-R from 224 patients. A single outcome variable based on the average
      standardized residual changes scores for these measures was derived to assess
      whether symptom severity at discharge was greater or less than predicted.
      Predictor variables were analysed using multiple regression. Chronicity variables
      predicted outcome, with patients hospitalized more than once and those with
      personality disorders more symptomatic than expected after treatment. Social
      support and personality variables failed to predict outcome; however, patients
      who scored higher on the MMPI Si scale were more symptomatic than expected at
      discharge. Although these results possess marginal clinical utility in terms of
      accounting for symptom change variation, this study overcame some methodological
      difficulties seen in prior day hospital literature. Future research should
      consider a prospective approach, including random treatment assignment,
      comprehensive and diverse outcome measures, and exploration of specific
      diagnostic groups.

PMID- 10880714
TI  - Physical morbidity in a psychiatric population in Nigeria.
AB  - The rate of physical morbidity amongst 191 psychiatric in-patients in a Nigerian
      general hospital was found to be 27.2%. Older psychiatric patients were observed
      to be significantly more likely to suffer from physical morbidity. Infective
      processes constituted 57.7% of the physical health problems identified in the
      study population. Organ systems most frequently involved were the central nervous
      system (mainly as acute organic brain syndrome from septicaemia) (28.9%),
      cardiovascular/haematological (19.2%), and gastrointestinal (17.3%). Over 70% of
      physical disorders remained undiagnosed by the referring sources. It is
      emphasized that adequate attention should be paid to the physical status of
      psychiatric patients (both new and old cases) at all levels of health care.
      Collaborative work between medicine and psychiatry should also be encouraged in
      developing countries, and this should extend beyond clinical services and
      training (undergraduate and postgraduate) into the areas of evaluative research.

PMID- 10880715
TI  - Cancer and the meaning of work.
AB  - The importance of work in patients with cancer has received relatively little
      attention. This article reviews the existing literature and uses case examples to
      illustrate the themes that characterize work-related distress. Whereas loss of
      occupational identity can be a source of significant anxiety and depression,
      continuing or returning to the workplace allows many patients to maintain a sense
      of normalcy or control. The experience of discrimination can become a focus for
      strong feelings about fairness. Clinicians need to both address work-related
      distress directly and appreciate the larger significance these themes may have in
      their patients' coping. A closer look at the importance of work in oncology
      suggests several areas for future research.

PMID- 10880716
TI  - Alcohol dependence among patients admitted to psychiatric emergency services.
AB  - We assessed the prevalence of alcohol dependence among patients examined in the
      psychiatric emergency service of a general hospital. We compared socio
      demographic data and psychiatric status of patients with and without alcohol
      dependence. One-hundred and four consecutive patients received by the psychiatric
      emergency service of Bichat-Claude Bernard Hospital (Paris, France) were
      assessed. Diagnosis of alcohol dependence, acute alcohol intoxication, and
      antisocial personality was determined according to DSM-IV criteria. Other
      psychiatric disorders were identified using a structured psychiatric interview,
      the Mini International Neuropsychiatric Interview (MINI). Prevalency rate of
      alcohol dependence was 37.5% among patients examined by the psychiatric emergency
      service. Alcohol-dependent patients were more often men than women and more often
      unemployed than non-alcohol-dependent psychiatric emergencies. They presented
      more dysthymia, acute alcohol intoxication, and antisocial personality than non
      alcoholic patients followed by the psychiatric emergency service. Attempted
      suicide was as frequent in alcohol-dependent patients (23%) as in other patients
      (29%). Alcohol-dependent patients consumed alcohol more often when alone, and
      their alcohol consumption began more frequently in the morning. Patients seen in
      a psychiatric emergency service must be identified as a population at risk for
      alcohol dependence (37.5%). Alcohol-dependent patients are more often men and
      have a higher rate of unemployment. They present significantly more often
      dysthymia and acute alcohol intoxication associated to alcohol dependence.

PMID- 10880717
TI  - Nicotine, brain nicotinic receptors, and neuropsychiatric disorders.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) represent a large family of
      ligand-gated cation channels with diverse structures and properties. In contrast
      to the muscular nAChRs, the physiological functions of neuronal nAChRs are not
      well defined to date. Behavioral studies indicate that brain nAChRs participate
      in complex functions such as attention, memory, and cognition, whereas clinical
      data suggest their involvement in the pathogenesis of certain neuropsychiatric
      disorders (Alzheimer's and Parkinson's diseases, Tourette's syndrome,
      schizophrenia, depression, etc.). For the majority of these disorders, the use of
      nAChRs' agonists may represent either a prophylactic (especially for Alzheimer's
      and Parkinson's diseases) or a symptomatic treatment. The possible mechanisms
      underlying these beneficial effects as well as the characteristics and potential
      therapeutic use of new, subtype-selective nAChRs agonists are presented.

PMID- 10880718
TI  - Diagnosis of inborn errors of metabolism.
AB  - Systematic detection of inborn errors of metabolism (IEM) has usually encountered
      difficulties in developing countries. We present our experience in a high-risk
      population in Mexico between 1973 and 1998 with particular reference to the last
      10 years, during which time infrastructure and support were considerably
      improved. Only disorders of intermediary metabolism were sought. The total number
      of patients studied is not available, but in the last 10 years, patients numbered
      5,186. Routine metabolic screening was performed on all patients, with additional
      tests according to the clinical picture and screening results. The referral
      criteria have increasingly diversified, one-third being neurological conditions.
      Of the referrals, 33.8% were from pediatricians (31.1% of whom were at critical
      medicine departments) and the remainder from specialists. The number of diagnosed
      patients has increased to 1 per 43.9 patients studied. Amino acid defects have
      been the most prevalent, the proportion of organic acid and carbohydrate
      disorders having increased in the last 10 years, associated with improved
      diagnostic facilities. The most frequently diagnosed diseases were PKU, type 1a
      glycogen storage, and maple syrup urine disease (MSUD), their frequency
      apparently varying among different regions of Mexico. Other results of our
      program include training of specialists and technicians, development of the Latin
      American Metabolic Information Network, a procedure to locally prepare a special
      food product low in phenylalanine for the treatment of PKU patients, and
      extension of approaches for these disorders to the investigation metabolic
      derangements of infant malnutrition. This work demonstrates that inherited
      metabolic diseases constitute a significant load in pediatric pathology and that
      their study can and should be pursued in developing nations.

PMID- 10880719
TI  - Neurocysticercosis and oncogenesis.
AB  - Recent studies suggest that neurocysticercosis may be a risk factor for human
      cancer. Pathogenetic mechanisms explaining possible oncogenic effects of
      cysticerci include the following: (a) parasite-induced modulation of the host
      immune response that may be associated with loss of regulatory mechanisms
      implicated in the immunological surveillance against cancer; (b) transfer of
      genetic material from the parasite to the host, causing DNA damage and malignant
      transformation of host cells, and (c) chronic inflammation with liberation of
      nitric oxide and inhibition of tumor suppressor genes. Further research is needed
      to confirm the potential role of cysticercosis in the development of cancer.
      These studies should determine the presence of cysticercotic factors responsible
      for the transfer of genetic material and potential mutations in the tumor
      suppressor genes in proliferating astrocytes surrounding cysticercotic lesions.
      Additionally, the complex interaction between the immune state of the host with
      variable cytokine release and the presence of inflammatory cells releasing nitric
      oxide that cause DNA damage and impair tumor suppressive mechanisms needs to be
      investigated.

PMID- 10880720
TI  - Antimutagenesis of beta-carotene to mutations induced by quinolone on Salmonella
      typhimurium.
AB  - BACKGROUND: Quinolone-induced mutagenesis in the Salmonella typhimurium hisG48
      strains suggests that these antibiotics are oxygen free radical generators. The
      use of beta-carotene as antioxidant was evaluated as an alternative to reduce
      oxidative cell damage in patients who need therapy with nalidixic acid,
      norfloxacin, or pipemidic acid. The studied beta-carotene (30%), used by
      pharmaceutical laboratories as dietary complements, was not toxic or mutagenic
      for the S. typhimurium TA102 strain at a dose equivalent to 1,500 I.U. At the
      studied concentrations, the evaluated antimutagen did not modify the minimum
      inhibitory concentration of nalidixic acid, norfloxacin, or pipemidic acid
      against uropathogenic Escherichia coli strains. METHODS: The mutagenic effect of
      nalidixic acid and norfloxacin against hisG48 strains was inhibited with 1500
      I.U. of beta-carotene. The antimutagenic effect of beta-carotene against
      mutations induced by pipemidic acid was observed even with 150 I.U. of beta
      carotene. The antimutagenic effect against mutations induced on S. typhimurium
      TA102 or TA104 strains was observed only when the aroclor 1254 rat-induced liver
      S9 mixture was used. RESULTS: This mutagenic effect was detected only when the
      strains were exposed to quinolones and the beta-carotene simultaneously with the
      S9 mixture, suggesting that quinolones induce oxygen free radicals that may be
      scavenged by beta-carotene. CONCLUSIONS: The antimutagenic effect of this vitamin
      A precursor is probably due to the active molecule of vitamin A, a desmutagen
      with the ability of radical capture. A diet rich in beta-carotene or vitamin A
      could be a good alternative to reduce genotoxic risk to patients being treated
      with quinolone.

PMID- 10880722
TI  - Immunoreactivity of common red blood cell antigens in cytoskeleton-free red blood
      cell microvesicles.
AB  - BACKGROUND: Cytoskeleton-free microvesicles can be generated from normal red
      blood cells (RBCs). These RBC vesicles maintain a representative sampling of the
      lipid bilayer and several membrane proteins. We investigated RBC antigen
      segregation and persistence of immunoreactivity in RBC microvesicles. METHODS:
      Cytoskeleton-free RBC microvesicles were generated from erythrocytes expressing
      known RBC antigens. Antigen segregation into vesicles was documented by
      immunospecific antigen-antibody binding using IgG eluates and 125I Protein A.
      125I Protein A counts per minute (cpm) ratios between antigen-positive vesicles
      sensitized with 11 eluates compared with those of vesicles incubated with normal
      human serum are reported. RESULTS: Cytoskeleton-free RBC microvesicles preserved
      the antigenic expression of the original RBC's. Differences in cpm between eluate
      sensitized vesicles and those incubated with normal human serum ranged from 3:1
      for the Fy(b) antigen to 65:1 for the D antigen. CONCLUSIONS: This study
      demonstrates that molecules bearing common RBC antigens segregate into
      microvesicles, fully preserving their epitope-bearing activity. The major
      proteins of the RBC cytoskeleton are not required for such antigen expression.

PMID- 10880721
TI  - Mg, Mn, and Co ions enhance the formation of Entamoeba histolytica cyst-like
      structures resistant to sodium dodecyl sulfate.
AB  - BACKGROUND: Entamoeba histolytica forms cyst-like structures (CLS) in PEHPS but
      not in TYS-33 medium. Sodium dodecyl sulfate [(SDS (0.1%)] dissolves most of them
      in 10 min, but not natural cysts. Chitin is responsible mainly for cyst wall
      resistance. Its synthesis depends on Mg(2)+, Mn(2)+, or Co(2)+, whose action is
      interactive. With the aid of the Simplex method, we analyzed the effect of 20
      blends of these cations to find the one that, when added to PEHPS, produced the
      highest proportion of CLS resistant to 1% SDS (RCLS). METHODS: The concentration
      of Mg(2)+, Mn(2)+, and Co(2)+ was determined in PEHPS and TYI-S-33 with a flame
      atomic absorption spectrometer. The proportion of RCLS produced in PEHPS with
      each ion blend was tested. The CLS and RCLS affinity to fluorescein wheat germ
      agglutinin (WGA/FITC), which binds chitin, was determined. RESULTS: PEHPS
      contained a similar concentration of Co(2)+ (0.52 microM) and 3.4 and 1.6 times
      more Mg(2)+ (798 microM) and Mn(2)+ (3.15 microM) than TYI-S-33, respectively.
      The proportion of RCLS increased gradually in PEHPS until reaching 3.6 +/- 1.43%
      with MgCl(2) 1.22 mM, MnCl(2) 14.44 mM, and CoCl(2) 19.44 mM (ion blend No. 20).
      Both CLS and RCLS bound WGA/FITC. The RCLS formed in the presence of ion blend
      No. 20 appeared wrinkled. CONCLUSIONS: Mg(2)+, Mn(2)+, and Co(2)+ enhanced the
      ability of PEHPS to form RCLS, possibly because these ions stimulated their
      chitin synthesis. Although ion blend No. 20 produced the highest proportion of
      RCLS, this high ion concentration may be toxic for encysting amebas.

PMID- 10880723
TI  - H-ras and Nm23-H1 gene expression and proteolytic activity in squamous cell
      carcinoma of the uterine cervix.
AB  - BACKGROUND: The invasive and metastatic potential of malignant cells results from
      complex interactions of numerous factors not yet fully understood. Genomic
      alterations such as ras overexpression and nm23-H1 inhibition have been found to
      be frequently associated with increased invasiveness in various cancers. On the
      other hand, secretion of different proteinases are necessary for malignant cells
      to traverse a network of matrix macromolecules, but the relationship between the
      genomic alterations and the proteolytic phenotype is still unclear. Our aim was
      to investigate whether the appearance of the proteolytic phenotype had any
      correlation with the expression of H-ras and nm23-H1 genes in carcinoma of the
      uterine cervix. METHODS: Twenty-five samples from patients with carcinoma of the
      uterine cervix at different clinical stages were studied. Cathepsin B1,
      plasminogen activator, and collagenase activity were assessed in tissue cytosols
      using specific synthetic oligopeptides as substrates. The expression of H-ras and
      nm23-H1 was investigated by means of immunohistochemistry and in situ
      hybridization. RESULTS: Our results showed that cathepsin B1 was the most
      consistently elevated proteinase, demonstrating a linear correlation with
      clinical staging. H-ras expression was found elevated in 40% of the cases. Nm23
      H1 protein immunoreactivity was positive in 40% of the cases. No correlation was
      found among H-ras, cathepsin B1 activity, and survival rate. Among cases with
      high cysteine proteinase activity, a different clinical behavior depending on the
      expression of Nm23-H1 was observed. The cases with Nm23-H1 protein had a markedly
      better survival rate than those lacking this protein. In contrast, the absence of
      Nm23-H1 in association with high cathepsin B1 activity was a clear indicator of a
      poor prognosis. CONCLUSIONS: These findings suggest a complex interaction between
      the proteolytic phenotype and the expression of H-ras and nm23-H1 genes in
      carcinoma of the cervix that influences the clinical behavior of the tumor.

PMID- 10880724
TI  - Thinner abuse alters optokinetic nystagmus parameters.
AB  - BACKGROUND: Deliberate self-inhalation of solvents such as thinner is a
      recognized problem in underdeveloped countries, with chronic abuse resulting in
      neurological impairment. In this article, we use electronystagmography (ENG) to
      study optokinetic nystagmus abnormalities (OKN) that may be induced by thinner
      consumption. METHODS: Twenty-five patients exposed to thinner for 5-20 years, in
      an irregular fashion of consumption, were recruited from a toxicologic center.
      Twenty-five control subjects were invited to participate as volunteers matched by
      age (+/-2 years) and gender. At the time of evaluation, all had abstained from
      intoxicants for at least 4 weeks. ENG recordings were performed by clinicians
      masked to the patient's group. Clockwise and counterclockwise stimulation were
      performed at 20 and 40 degrees /sec. RESULTS: None of the patients showed
      spontaneous nystagmus during the test period. Differences between thinner abusers
      and controls on clockwise and counterclockwise OKN on number of beats of
      nystagmus elicited on the 40 degrees /sec velocity were identified. The thinner
      abusers group showed a lesser number of nystagmus (p level was 0.02 and 0.005,
      respectively). CONCLUSIONS: The present results confirm the sensibility of OKN as
      an early marker of solvent abuse. These results were obtained in middle-term
      chronic exposure to solvent mixtures and are in favor of both cortical and
      brainstem dysfunction.

PMID- 10880725
TI  - Preirradiation ifosfamide, carboplatin, and etoposide for the treatment of
      anaplastic astrocytomas and glioblastoma multiforme: a phase II study.
AB  - BACKGROUND: Central nervous system (CNS) tumors are the second most common
      pediatric tumors. Astrocytomas represent 35% of all CNS tumors in children.
      Traditional treatment of anaplastic astrocytoma (AA) and glioblastoma multiforme
      (GM) consisting of surgery-radiotherapy-chemotherapy with nitrosoureas has
      resulted in a survival rate of 26% at 1 year. Neoadjuvant chemotherapy has proven
      good results in the treatment of other solid tumors. Chemotherapy with
      ifosfamide, carboplatin, and etoposide (ICE) permits synergism among the
      different drugs and sensitizes the tumor to radiotherapy. Our objective was to
      evaluate the efficacy, security, and survival rate of postoperative chemotherapy
      with ICE in pediatric patients with AA or GM. METHODS: Phase II study. We
      evaluated 11 children with AA or GM who had received no prior treatment. A
      magnetic resonance image (MRI) study of the tumor was made after surgery to
      evaluate residual tumor and routine laboratory analysis. Chemotherapy with
      carboplatin, ifosfamide and etoposide was given every 3 weeks for four courses.
      MRI studies were repeated after the second and last courses and laboratory
      analyses were carried out before each course to evaluate toxicity. Each patient
      then received hyperfractionated radiotherapy and a final MRI was done at the end
      of the treatment. RESULTS: Sixty percent of the patients had partial response,
      30% complete response after two courses, and 60% of CR after four courses.
      Supratentorial and infratentorial tumors had a good response to chemotherapy.
      Brainstem tumors had an initial response after two courses and then increased in
      size. AA was the tumor with the greatest reduction of residual tumor after
      treatment. Overall and free survival at 53 months was 70%. To date, three
      patients have died secondary to tumoral progression. There have been no relapses
      in the seven patients with a CR. CONCLUSIONS: Postoperative chemotherapy with ICE
      reduces the tumor size and increases the survival rate of pediatric patients with
      malignant astrocytomas with minimal toxicity. Brainstem responded poorly to
      treatment.

PMID- 10880726
TI  - Analgesic efficacy and bioavailability of ketorolac in postoperative pain: a
      probability analysis.
AB  - BACKGROUND: The analgesic efficacy and bioavailability of 30 mg intramuscular
      ketorolac was studied in 24 patients with severe or very severe postoperative
      pain. METHODS: Pain and pain relief were determined by a five-point verbal rating
      scale and data were submitted to a probability analysis. Ketorolac plasma levels
      were determined by high-performance liquid chromatography. RESULTS: Two patients
      chose not to finish the study; 22 patients completed the study achieving at least
      good pain relief. Of these 22 patients, 13 reached complete pain relief.
      Ketorolac was rapidly absorbed. Notwithstanding, pain relief increased gradually,
      showing considerable delay with regard to plasma concentrations. Analysis of the
      probability-time curves revealed that 25% of the patients obtained moderate pain
      relief at 7 min after ketorolac administration, 50% at 11 min, 75% at 29 min, and
      95% at 60 min. Good pain relief was achieved in 25, 50, and 75% of the patients
      at 1.1, 1.8, and 2.7 h, respectively. Complete pain relief was achieved in 25%
      and 50% of the patients at 2.6 h and 3.7 h, respectively. The probability of
      exhibiting an acceptable pain relief in responsive patients for more than 5 h was
      0.97. No serious side effects were detected. CONCLUSIONS: Results show that 30 mg
      intramuscular ketorolac is an adequate treatment for postoperative pain in the
      Mexican population. Therefore, the use of higher doses is not justified. Due to
      gradual installation of analgesia, administration of additional analgesic
      medication before 1 h is not recommended.

PMID- 10880727
TI  - Development and application of reflexodent in the quantitative functional
      evaluation of chewing control in patients with temporomandibular joint
      dysfunction and a control group.
AB  - BACKGROUND: There has been controversy with respect to the diagnostic value of
      the inhibitory masseteric reflex in temporomandibular joint dysfunction (TMJD)
      because the whole reflex response was not considered. The purpose of this study
      was to characterize the reflex changes that occur in patients with different
      levels of TMJD and in a control group. METHODS: Eighty-nine patients (ages 31.14
      +/- 12.74 years) divided into three groups were studied and compared. The control
      group was without TMJD (n = 30), with moderate symptoms (n = 30), and with severe
      symptoms (n = 29). Using an instrument and a software program developed by our
      group (Reflexodent), the masseteric inhibitory reflex was studied. The
      electromyography record (EMG) was captured with surface electrodes and the
      inhibitory reflex was produced by tapping the chin. The EMG signal was processed,
      filtered, and averaged with the Reflexodent. Twenty series of records were
      applied to each patient. The faulty inhibitory area, the area's relation
      (potentiation/inhibition) regarding the values of healthy subjects previously
      characterized, and the bilateral symmetry were measured. RESULTS: Discriminate
      analysis showed a statistically significant correlation between clinical groups
      and electromyographic findings. Statistical function explained 91.8% of the
      discrimination among groups (canonical correlation = 0.918, chi(2) = 164.435, p
      <0.001). CONCLUSIONS: The study of whole inhibitory masseteric reflex and the
      Reflexodent technique are useful as a diagnostic tool to evaluate TMJ illness in
      the dental clinic.

PMID- 10880728
TI  - Plasma level monitoring of oxcarbazepine in epileptic patients.
AB  - BACKGROUND: Despite the wide use of oxcarbazepine (OXC) there is little data
      concerning the usefulness of plasma level monitoring with this drug in Mexican
      patients with epilepsy. The purpose of the present study was to determine whether
      OXC levels correlate with dose, age, weight, or drugs used concomitantly.
      METHODS: Plasma levels of the antiepileptic drug OXC were evaluated in 214
      patients with epilepsy. In each patient, plasma MHD (10-hydroxycarbazepine, the
      main metabolite of OXC) concentration was determined. Additionally, plasma
      protein binding was determined in 30 patients and affinity to red blood cells
      (RBCs) was evaluated in 50 patients. RESULTS: Our results showed that the mean
      plasma level of MHD was 15.34 microg/mL, mean protein binding ranged between 30
      40%, and the mean RBC concentration was 18.38 microg/mL. A relationship between
      dose/weight and plasma concentration was found (r = 0.5149, p <0.001). In
      addition, a linear relationship between plasma and RBC concentration was
      established (r = 0.8806, p <0.0001). CONCLUSIONS: These results suggest that for
      OXC, routine RBC concentrations are not necessary to make drug adjustments.

PMID- 10880729
TI  - Allogeneic bone marrow transplantation for chronic myeloid leukemia: a single
      center experience.
AB  - BACKGROUND: Bone marrow transplantation (BMT) is the therapy of choice for
      patients with chronic myeloid leukemia (CML) who have a human leukocyte antigen
      (HLA)-identical donor and are under 50 years of age. METHODS: Here, 45 patients
      with CML were treated with busulfan (Bu) 16 mg/kg and cyclophosphamide (Cy) 120
      mg/kg before allogeneic BMT from an HLA-identical sibling 27 (60%) or a 1-antigen
      mismatch donor 18 (40%). Eighteen patients (40%) were in the early chronic phase
      (CP) and 27 (60%) in late CP. We used cyclosporin-A (CsA) in 20 patients and
      cyclosporin-A-methotrexate (CsA-MTX) in 25 for graft-vs.-host disease (GVHD)
      prophylaxis. RESULTS: We observed a high incidence of acute and chronic GVHD (69%
      and 67%, respectively). A multivariate analysis identified differences in the sex
      of the donor and the recipient (p = 0.03) and grade III-IV acute GVHD (p =
      0.0001) as significant adverse influences on disease-free survival. Age, sex,
      chronic GVHD, disease phase, one antigen-mismatch and use of CsA or CsA-MTX had
      no statistical significance. The 3-year probabilities of relapse, disease-free
      survival, and overall survival were 11%, 55%, and 60%, respectively. Transplant
      related mortality occurred in 31% of the cases. The high frequency of GVHD is
      explained by HLA determination by serological typing, differences in sex between
      the donor and recipient, and a high proportion (40%) of 1 antigen-mismatch
      donors. CONCLUSIONS: BMT is a procedure feasible for patients with CML in early
      and late chronic phase and even in those with an HLA non-identical donor.
      Strategies directed to decrease acute GVHD could improve the outcome of these
      patients.

PMID- 10880730
TI  - Leukocyturia in women with diabetes and its clinical implications.
AB  - BACKGROUND: Urinalysis is one of the most common studies performed on the
      diabetic patient at every visit. The presence of leukocyturia is relatively
      common but it is not clear what the attitude of the physician toward this
      particular finding should be. The main objective of the present study was to
      investigate the clinical significance of leukocyturia in diabetic women. METHODS:
      Ninety-eight diabetic women (84.7% type 2) aged 57 +/- 13 years who were being
      seen at the diabetic out-patient clinic were randomly selected. All patients
      underwent a clinical and gynecologic examination and a urinalysis. A Papanicolaou
      smear and a urine culture were also obtained. RESULTS: The overall prevalence of
      leukocyturia (>5 cells/high power field (hpf)) was 46.5%. Patients with urinary
      tract infections (UTI) were 7.5 times more likely to have leukocyturia, while a
      leukocyte count <5cells/hpf predicted the absence of UTI in 96% of the women. In
      the comparison of patients with and without leukocyturia, we found that
      proteinuria (p = 0.06) and bacteriuria (p <0.002) were more common in the women
      with leukocyturia. A significant association with leukorrhea was not
      demonstrated. The empirical use of antibiotics was 12 times more frequent in the
      patients with leukocyturia. CONCLUSIONS: A urinary culture should be requested in
      all diabetic patients with leukocyturia. The possibility of a UTI is remote when
      leukocyturia is absent.

PMID- 10880731
TI  - Hypothalamic dopaminergic tone and prolactin bioactivity in women with polycystic
      ovary syndrome.
AB  - BACKGROUND: The present study was carried out to investigate the functional
      significance of the reduced dopaminergic tone in subjects affected with
      polycystic ovary syndrome (PCOS). METHODS: Our group evaluated the response of
      pituitary PRL, LH, FSH, and TSH to the administration of a single 10-mg oral dose
      of the dopamine (DA) receptor antagonist metoclopramide in lean (n = 7) and obese
      (n = 8) PCOS women and in 11 regularly cycling age- and weight-matched controls
      (six lean and five obese). In addition, circulating PRL bioactivity was evaluated
      by its mitogenic activity on a lymphoma cell bioassay. RESULTS: Oral
      administration of metoclopramide resulted in a significant increase in serum PRL
      in all subjects; however, the highest increments, regardless of body mass index
      (BMI), were observed in control women (p <0.005). Measurements of PRL mitogenic
      activity on the Nb2 lymphoma cell bioassay revealed a significant increase in the
      bioactive/immunoreactive (B/I) ratio of PRL under basal and stimulated conditions
      in obese PCOS subjects (p <0.05). Mean fasting glucose/insulin and
      glucose/insulin-AUC ratios were significantly lower (p <0.001) in obese PCOS when
      compared with all other groups. CONCLUSIONS: These data support the existence of
      low DA hypothalamic tone in PCOS women that is likely involved in the
      inappropriate LH and PRL secretion frequently seen in this syndrome. In addition,
      our results suggest changes in PRL bioactivity in obese PCOS that may play a role
      in the development of hyperinsulinemia; however, whether PRL has a functional
      significance in the development of the metabolic disturbances frequently seen in
      PCOS remains to be elucidated.

PMID- 10880732
TI  - Impact of physical functioning of health status on hospitalizations, physician
      visits, and costs in diabetic patients.
AB  - BACKGROUND: The objective was to determine the impact of the physical functioning
      of diabetic patients on hospitalizations, physician visits, and costs using
      Medicare data. METHODS: A total of 12,863 people who completed the interview of
      the 1993 Medicare Current Beneficiary Survey (MCBS) was studied. A diabetic
      patient was defined as a patient who answered this question positively: Are you
      diabetic? The final sample was made up of 10,517 non-diabetic patients and 2,003
      diabetic patients. The Activity Daily Living (ADL) Scale of the MCBS was used to
      assess physical functioning. Hospitalizations, physician visits, and costs were
      obtained from the Medicare database. RESULTS: We found that diabetic patients had
      a worse perception of physical functioning than non-diabetic patients (ADL
      disability score 8.47 +/- 15 vs. 5.8 +/- 13). Patients with diabetes consume more
      resources and the costs associated with their medical care are higher than for
      non-diabetic patients (mean total reimbursement in 1993 for diabetics was 6,847
      +/- 15,071 USD vs. 3,773 +/- 9,971 USD). Total costs were highly correlated with
      the ADL disability score (r = 0.75). CONCLUSIONS: Self-perception is highly
      correlated with the care cost of patients with diabetes.

PMID- 10880733
TI  - Anergic T cells as active regulators of the immune response.
AB  - T cell anergy is one of the mechanisms leading to the establishment and
      maintenance of peripheral tolerance. Recent data from our and other laboratories
      indicate that anergic T cells are not functionally inert but in fact are capable
      of regulating the immune response in an active manner. In this review, we
      describe our viewpoint on how anergic self-reactive T cells could contribute to
      regulation of the immune response.

PMID- 10880734
TI  - Synthetic peptides that inhibit binding of the collagen type II 261-273 epitope
      to rheumatoid arthritis-associated HLA-DR1 and -DR4 molecules and collagen
      specific T-cell responses.
AB  - Copolymer 1 [Cop 1, poly (Y, E, A, K)] is a random synthetic amino acid copolymer
      effective in the treatment of relapsing forms of multiple sclerosis (MS), a
      disease that is linked to HLA-DR2 (DRB1*1501). Another copolymer [poly (Y, A, K)]
      was also identified that binds to rheumatoid arthritis (RA)-associated HLA-DR1
      (DRB1*0101) or HLA-DR4 (DRB1*0401) molecules and inhibits the response of HLA-DR1
      and -DR4-restricted T cell clones to an immunodominant epitope of collagen type
      II (CII) 261-273 (a candidate autoantigen in RA). In the present study various
      peptides have been synthesized based on binding "motifs" of Cop 1 for HLA-DR1 and
      -DR4 molecules. Those peptides with K at P-1 or K at P8 were particularly
      effective as inhibitors of binding of CII 261-273, of Cop 1 and of the influenza
      virus hemagglutinin peptide 306-318 to these class II proteins. Moreover, several
      of them were also potent inhibitors of the CII 261-273-reactive T cell clones.
      These findings suggest that small peptides or their more stable derivatives may
      be able to substitute for copolymers in the treatment of RA, and by implication
      of MS.

PMID- 10880735
TI  - Th1- and Th2-type lymphokine-assisted induction and release of chemokine
      receptors from primary human trophoblast cells.
AB  - Chemokine receptors (CCRs) have been demonstrated to facilitate the entry of HIV
      in different cell types of infected individuals, including CD4(+) T cells and
      dendritic cells. The natural or inducible expression of CCRs on trophoblast cells
      could provide a valid mechanism for the in utero transmission of HIV from mother
      to fetus. Because of the rapid turnover of these receptors, we attempted to
      define the natural and inducible expression of surface CCR3 and CXCR4 on primary
      human trophoblasts during short periods of cell culture. In the absence of any
      external stimulus the expression of CCR3 and CXCR4 varied from 1% to 24%. Kinetic
      experiments show that the levels of both CCR3 and CXCR4 reach a peak of
      expression after 6 h of culture, whereas by 24 h they have almost disappeared. In
      the presence of IFN-gamma, CCR3 is showing an increasing pattern of expression
      after 4 h of incubation, reaching highest levels after 24 h of culture, whereas
      CXCR4 is kept at lower levels as compared with nontreated cells. Furthermore, in
      the presence of IL-4, CCR3 expression declines from 2 to 8 h of culture to
      increase again at 24 h, where 50% of the cell population is expressing the
      receptors. Under the IL-4 stimulus, CXCR4 shows a peak of expression at 8 h of
      culture. An interesting feature of this study is that we were able to detect
      soluble CCR activity in the culture supernatants of trophoblast cells, which
      followed an inverse pattern of this of surface expression. Thus, the inability of
      many laboratories to detect high levels of CCRs in placentae of HIV infected
      mothers may be due on these fast turnover of these receptors, which by the
      assaying time have either been released in the culture medium or been
      internalized to the cell.

PMID- 10880736
TI  - CD28/CTLA-4 and CD80/CD86 costimulatory molecules are mainly involved in
      acceptance or rejection of human liver transplant.
AB  - CD28/CTLA-4 interactions with their specific B7-ligands (CD80 and CD86) have
      decisive roles in antigenic and allogenic responses. Recently, experimental
      transplant studies demonstrated that donor-specific tolerance is achieved by
      blocking these interactions. The present study analyzes the expression of these
      co-stimulatory molecules in peripheral blood cells from 74 liver recipients and
      in 16 liver biopsies, which were classified into acute-rejection (AR, n = 27) and
      nonacute-rejection (NAR, n = 47) groups, as well as their influence on the in
      vitro response of in vivo allosensitized cells. The results clearly indicate that
      in human liver transplant too, B7 and CD28/CTLA-4 expression on B and CD4(+)
      peripheral lymphocytes respectively, contributes to graft acceptance or
      rejection, and appears to be of crucial importance in modulating the host
      alloresponse and specific-CTL generation. In the NAR-group, costimulatory
      molecule expression remained at basal levels after transplant, whereas in the AR
      group these molecules were significantly upregulated on days of AR. CTLA-4 was
      observed in the infiltrating lymphocytes in most of the biopsies, but CD80 or
      CD86 were not. Moreover, specific cytotoxicity from the in vivo primed cells was
      clearly suppressed in the NAR-patients with low co-stimulatory molecule
      expression, whereas this activity was not modified but rather stimulated in the
      AR-group. Together, these findings indicate that intervention of CD28/CTLA-4/B7
      signaling could be therapeutically useful in clinical transplantation.

PMID- 10880737
TI  - Significance of transporter associated with antigen processing gene polymorphism
      in living related renal transplantation.
AB  - The HLA class I and class II mediated antigen presentation plays a major role in
      the initiation of immune response and the development of acute rejection after
      transplantation. The purpose of this study was to examine whether MHC-encoded
      antigen processing (TAP1, TAP2, LMP2, DMA and DMB) gene polymorphisms were
      associated with the incidence and the severity of acute rejection after renal
      transplantation. We studied a selected population of 112 pairs of donors and
      recipients who underwent living-related renal transplantation. They were divided
      into 3 groups: rejection-free (Group A, n = 51), steroid-sensitive rejection
      (Group B, n = 31) and steroid-resistant rejection (Group C, n = 30). The
      frequency of TAP2*0103 (41.2%) was significantly higher in the donors of Group A
      than that of Group B (12.9%, p = 0.0070, pc = 0.0280) or Group C (16. 7%, p =
      0.0225, pc = 0.0900). No significant difference was observed in the allelic
      frequencies of the TAP1, LMP2, DMA, and DMB genes in the donors or recipients
      among Groups A, B, and C. This result supported the idea that the TAP2 gene
      polymorphism might be functionally related to antigen presentation. It also
      suggested that donor's antigen presenting cells with the TAP2*0103 allele would
      have the attenuated efficacy in the presentation of allospecific antigens to
      recipient's T cells.

PMID- 10880738
TI  - T cell repertoire in the liver of patients with primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune chronic liver disease
      characterized by the destruction of the bile ducts with an accumulation of
      lymphocytes. To investigate the roles of T cells accumulating around the bile
      ducts, we analyzed the clonality of alphabeta T cell populations in the livers of
      patients with PBC by size spectratyping and sequencing of the T cell receptor
      (TCR) Vbeta transcripts.TCR Vbeta spectratyping of PBC patients showed several
      skewed complementarity determining region 3 (CDR3) size patterns suggestive of
      clonal predominance as well as Gaussian-like patterns suggestive of polyclonal
      expansion. We observed Vbeta4 clones sharing the Gly (G)-G motif in the CDR3 nDn
      regions and a Vbeta4-Jbeta2.7 combination in three patients bearing HLA-DR2 and 
      DQ1. G-Leu (L)-Ala (A) or G-L motifs were also seen in the nDn regions of Vbeta17
      with Jbeta2.1 of the two patients having HLA-A26. However, there were no whole
      CDR3-shared clones in any of the patients. In conclusion, we have observed that T
      cell clones are heterogeneous in each patient, but that they have some common
      motifs in the TCR Vbeta CDR3. We strongly suggest that these clonally expanded T
      cells might be involved in the immunopathogenesis of PBC.

PMID- 10880739
TI  - Prostanoids in human colonic mucosa: effects of inflammation on PGE(2) receptor
      expression.
AB  - Although the tissue concentration of PGE(2) is heightened 3-fold or more during
      mucosal inflammation, the cellular targets of prostanoids in human mucosa and the
      resulting changes in cell physiology have not been fully explored. We used a
      panel of immunoglobulin and mRNA probes in order to localize and quantitate the
      four member EP family of prostanoid receptors for binding PGE(2) to cells of
      histologically normal and inflamed human colonic mucosa, and then examined
      prostanoid-induced changes in mucosal lymphocyte function. Prostanoid receptors
      were selectively expressed on a limited number of human colonic mucosal cells;
      EP(4) alone was expressed on lamina propria mononuclear cells. Dual
      immunostaining in situ identified the CD3(+) T lymphocyte as a major EP(4)
      receptor-bearing cell in normal mucosa. Flow cytometry of isolated cells showed
      that 19.2% of lamina propria mononuclear cells were EP(4)(+), and almost 30% of
      these were CD3(+). In situ hybridization with digoxygenin-labeled RNA probes
      largely confirmed this localization. During inflammation, mucosal T lymphocytes
      showed a significant enhancement in EP(4) immunoreactive receptor protein.
      Computer-assisted densitometry of single cells demonstrated an increase in
      fluorescence intensity from 4.8 +/- 1.8 to 8.6 +/- 1.8 (p < 0.04). The effects of
      PGE(2) included a 35% reduction in T lymphocyte IL-2 secretion. COX 1(+) lamina
      propria cells nearly doubled in number during inflammation; expressed a T
      lymphocyte marker; but retained an unchanged quantity of immunoreactive COX 1
      protein per cell. The number of newly appeared COX 2(+) lymphocytes remained <50%
      that of COX 1(+) cells. A major perturbation in the number and distribution of
      PGE(2) receptors and enzymes for prostanoid synthesis occurs in chronic
      inflammation of the colon, with consequences for mucosal T lymphocyte function.

PMID- 10880740
TI  - gamma-aminobutyric acid-transaminase activity in the human thymus after
      administration of interferons.
AB  - The purpose of this article is to study the amounts of gamma-aminobutyric acid
      transaminase (GABA-t) during immune response in the human thymus. GABA-t was
      studied by biochemical and histochemical methods in 7 immunostimulated (treated)
      and 7 non-immunostimulated (untreated) patients (4 young adult, age range: 24-36
      years; 3 older adult, age range: 56-66 years). Immunostimulation was performed
      using interferon drugs for 6 months. After the histoenzymatic staining of GABA-t
      activity, the slides containing the samples of thymus of treated and untreated
      patients underwent quantitative analysis of images. The present results provide
      direct evidence that the immune response increases the level of GABA-t contained
      in vessels, parenchyma and nerve fibers of the thymus. Treatment with interferon
      is also capable of increasing the protein content of the thymus. The biochemical
      data together with the histoenzymatic results provide evidence for a localization
      of GABA-t in the thymic gland. Moreover, gamma-aminobutyric acid can be
      considered as one of the linking molecules between the immune and nervous
      functions of the human thymus.

PMID- 10880741
TI  - A limited number of HLA epitopes are recognized from HLA class I-specific
      antibodies detected in the serum of sensitized patients.
AB  - The goal of this study was to evaluate the epitope specificity of HLA class I
      specific antibodies detected in the serum of sensitized patients awaiting
      retransplantation. The study group consisted of 22 sensitized from previous graft
      patients, who produced stable IgG HLA class I-specific antibodies. A total of 60
      serum samples were screened and analyzed by two techniques in parallel: the
      antihuman globulin augmented CDC (AHG-CDC) technique and an ELISA technique. All
      recipients and donors were typed for class I HLA antigens by a standard
      lymphocytotoxicity technique. The epitope identification was based on class I HLA
      antigens sequencing, where the multiple immunogenic epitopes are differentially
      shared among various HLA antigens. The unique epitope configuration on one HLA
      antigen represents the private epitope of the specific HLA antigen while epitopes
      shared by more than one HLA antigen represent public determinants. In some HLA
      antigens (HLA-A1), more than one private epitope has been defined, while in
      others (HLA-B35, -B51), the private epitopes are not yet known. In a total of 36
      antibody reactivity patterns, the majority of the definable IgG HLA class I
      specific antibodies corresponded to the A-locus (75%), and only 25% had
      specificities against the B-locus antigens, although the number of
      incompatibilities concerning both loci were almost identical (29 for the HLA
      antigens of the A-locus and 26 for those of B-locus). All patients produced HLA
      class I-specific antibodies with specificities against the private epitopes of
      the immunogenic mismatched HLA antigen(s). In 6/21 cases (28.6%), HLA class I
      alloreactivity spreading to nongraft HLA antigens was detected and 9 public
      (shared) immunogenic alloepitopes were recognized. In conclusion, appling the
      epitope analysis of HLA class I-specific antibodies produced by sensitized from
      previous graft patients, we were able to define the immunogenic alloepitopes. We
      consider that the immunogenic alloepitopes, during transplantation course, are
      mainly private epitopes of mismatched HLA antigens and, in certain cases, shared
      epitopes between the donor alloantigens and other HLA antigens. This knowledge
      may offer the potential of transplanting sensitized patients through improved
      donor selection.

PMID- 10880742
TI  - Polymorphisms in the HLA-linked olfactory receptor genes in the Hutterites.
AB  - Genes in the MHC have been associated with mate choice and odor preferences in a
      variety of animals. Although the role of HLA genes in human mate choice has been
      controversial, studies in the Hutterites have demonstrated fewer than expected
      numbers of couples who match for an HLA haplotype, suggesting that in this
      population there is avoidance of mates with HLA haplotypes similar to one's own
      haplotype. Recently, 18 olfactory receptor (OR) genes have been mapped to the HLA
      region, telomeric to the HLA-F locus, providing a potential mechanism for HLA
      based odor recognition and perhaps mate preferences in humans. We screened a
      sample of Hutterites with diverse HLA haplotypes for polymorphisms in the HLA
      linked olfactory receptor gene, FAT11, by sequencing, denaturing high performance
      liquid chromatography, and allele-specific oligo dot-blotting. Three single
      nucleotide polymorphisms were detected in the single translated exon of this
      gene, all of which resulted in amino acid substitutions (Phe587Leu, Ala642Val,
      and Thr1157Ala). The FAT11 Phe587- Val642-Ala1157 allele occurred on 17 different
      HLA haplotypes, the Leu587-Ala642-Ala1157 allele on 15 haplotypes, the Phe587
      Ala642-Ala1157 allele on 16 haplotypes, and the Phe587-Ala642-Thr1157 allele on a
      single haplotype. Thus, four alleles of the FAT11 gene are present in the
      Hutterites. This level of variation in the FAT11 gene alone may not be sufficient
      to contribute to the observed patterns of mate choice in the Hutterites and to
      individual variation in odor preferences.

PMID- 10880743
TI  - Nomenclature for factors of the HLA system, update march 2000

PMID- 10880746
TI  - Origins and functions of phagocytes in the embryo.
AB  - To review the data on the origins, phenotype, and function of embryonic
      phagocytes that has accumulated over past decade. Most of the relevant articles
      were selected based on the PubMed database entries. In additional, the
      Interactive Fly database (http://sdb.bio. purdue.edu/fly/aimain/1aahome.htm),
      FlyBase (http://flybase.bio. indiana.edu:82/), and TBase (http://tbase.jax.org/)
      were used to search for relevant information and articles. Phagocytes in a
      vertebrate embryo develop in two sites (yolk sac and liver) and contribute to
      organogenesis in part through their ability to recognize and clear apoptotic
      cells. Yolk sac-derived phagocytes differ in differentiation pathway and marker
      gene expression from macrophages produced via classic hematopoietic progenitors
      in the liver. We argue that yolk sac-derived phagocytes constitute a separate
      cell lineage. This conclusion raises the question of whether primitive phagocytes
      persist into the adulthood.

PMID- 10880747
TI  - Granulocyte colony-stimulating factor perturbs lymphocyte mitochondrial function
      and inhibits cell cycle progression.
AB  - Sera from healthy subjects receiving recombinant human granulocyte colony
      stimulating factor (rHuG-CSF) to mobilize CD34(+) peripheral blood progenitors
      (PBPC) have been recently shown to induce unresponsiveness of allogeneic
      lymphocytes to mitogenic challenge. In the present investigation, the effects of
      rHuG-CSF on the early stages of lymphocyte activation-induced apoptosis and on
      lymphocyte cell cycle entry were evaluated. Sera were obtained from HLA-identical
      donors receiving rHuG-CSF to mobilize CD34(+) PBPC for allogeneic
      transplantation. Normal peripheral blood mononuclear cells (PBMC) were challenged
      with phytohemagglutinin (PHA) in the presence of serum collected before (preG) or
      after rHuG-CSF administration (postG). Mitochondrial function, that is,
      incorporation of 3,3'-dihexyloxacarbocyanine iodide [DiOC(6)(3)] and generation
      of reactive oxygen species (ROS) as well as expression of c-Myc and Bcl-2 family
      members (Bcl-2, Bcl-X(L), Bax) were evaluated by multiparameter flow cytometry.
      The activation-induced fragmentation of genomic DNA was detected by highly
      sensitive LM-PCR assay.CD4(+)DiOC(6)(3)(low) and CD8(+)DiOC(6)(3)(low) T
      lymphocytes increased and reached 32% (range 27%-38%) and 20% (range 15%-23%) of
      circulating T cells, respectively, on day 4 of rHuG-CSF administration.
      Hypergeneration of ROS could be demonstrated in 65% (range 58%-82%) of CD4(+) T
      lymphocytes and in 0.4% (range 0.2%-0. 8%) of circulating CD8(+) T cells. rHuG
      CSF determined no alteration of mitochondrial function if added to allogeneic
      PBMC in vitro, thus suggesting indirect effects mediated by soluble factors; on
      the contrary, when PBMC were challenged with PHA in the presence of postG serum,
      both perturbation of mitochondrial transmembrane potential (Deltapsi(m)) and
      hypergeneration of ROS were induced, and lymphocytes were predominantly arrested
      in a G(0) -like phase of the cell cycle and displayed genomic DNA fragmentation.
      Interestingly, the preincubation of PBMC with a blocking antibody directed
      against CD95 abrogated the perturbation of lymphocyte Deltapsi(m), suggesting
      that the CD95 signaling pathway might play a role in the induction of apoptosis
      after PHA stimulation in the presence of postG serum. Moreover, Bax protein was
      overexpressed in postG (median fluorescence intensity = 180, range 168-186)
      compared with preG cultures (median fluorescence intensity = 75, range 68-80; p <
      0.01), while no differences in Bcl-2, Bcl-X(L), and c-Myc staining intensity were
      observed. Our findings demonstrate a humoral-mediated rHuG-CSF-induced
      dissipation of lymphocyte mitochondrial Deltapsi(m); these effects might be
      mediated by Bax overexpression, with imbalance between apoptosis-promoting and
      apoptosis-inhibiting Bcl-2 family members and with subsequent induction of
      mitochondrial permeability transition. Whether immune dysfunction will favorably
      impact on incidence and severity of acute graft vs host disease after allogeneic
      PBPC transplantation remains to be determined.

PMID- 10880748
TI  - Stem cell factor and interleukin-4 increase responsiveness of mast cells to
      substance P.
AB  - The response of mast cells (MC) to non-IgE-mediated stimulation is critically
      dependent on the population of MC examined. The neuropeptide Substance P (SP) has
      been reported to activate connective tissue-type MC (CTMC), while mucosal MC
      (MMC) are not activated by SP. We examined the effect of stem cell factor (SCF)
      plus interleukin-4 (IL-4) on SP-initiated activation of bone marrow-derived MC
      (BMMC). Mouse MC, derived from a culture of BM cells with IL-3, were subsequently
      treated with recombinant SCF plus IL-4 for 6 days. Responsiveness to SP was
      monitored measuring beta-hexosaminidase and lipid mediator release. Histochemical
      staining, histamine analysis, and granule protease expression were achieved to
      characterize the cells. In contrast to IL-3 grown cells, SCF/IL-4-exposed cells
      showed functional responsiveness to release beta-hexosaminidase (42.25% +/- 1.46%
      at SP concentration of 100 microM) and produce leukotriene C(4) (LTC(4)) (7.4 +/-
      1.5 ng/10(6) cells)/prostaglandin D(2) (PGD(2)) (2.0 +/- 0.3 ng/10(6) cells) upon
      stimulation by SP. The increase in sensitivity of the cells to SP was not due to
      differentiation into CTMC, as the cells remained heparin negative. Both SCF and
      IL-4 were needed because SCF or IL-4 alone were insufficient to keep cells viable
      after 3 to 4 days post coculture. SP-induced secretion from BMMC cultured in
      medium containing SCF plus IL-4 (25.76% +/- 1.83%) was higher in comparison with
      cells cultured with SCF plus IL-3 (8.85% +/- 0.68%).These findings indicate that
      temporal changes in cytokine expression can influence the sensitivity of MC to
      non-immunologic stimuli. Local cytokine production leading to an increase in MC
      responsiveness to SP and inducing secretion of granule content and lipid
      generation may, therefore, propagate and worsen inflammatory conditions.

PMID- 10880749
TI  - Proliferation and cell death of embryonic primitive erythrocytes.
AB  - Erythropoietin (EPO) is the principal regulator for the production of adult-type
      definitive erythrocytes (EryD). EPO not only stimulates both the proliferation
      and differentiation of EryD progenitors, but also maintains the viability of EryD
      progenitors. Compared to the abundant knowledge about the function of EPO in EryD
      production, the roles of EPO in the production of embryonic-type primitive
      erythrocytes (EryP) are less clear. The effects of EPO on EryP proliferation and
      differentiation were investigated using EryP purified from developing mouse
      embryos and the cells obtained from mouse embryonic stem cells using an in vitro
      differentiation induction. Immature EryP of both in vivo and in vitro origin
      responded to EPO stimulation and underwent apoptosis with EPO deprivation. In
      contrast, there were no significant differences between the cultures with and
      without EPO, when fully mature EryP were examined, that is, EryP lost its
      dependency on EPO stimulation with maturation. These results show that EPO
      functions as a survival factor for immature embryonic EryP as well as immature
      EryD progenitors.

PMID- 10880750
TI  - Neonatal gene therapy. transfer and expression of exogenous genes in neonatal
      sheep following direct injection of retroviral vectors into the bone marrow
      space.
AB  - We investigated whether gene transfer into hematopoietic cells could be achieved
      by direct injection of retroviral vector supernatant into the bone marrow space
      of newborn sheep. Six sheep (5 weeks old) were injected bilaterally with either 1
      mL of G1nBgSvNa8.1 vector supernatant (titer: 1 x 10(7)) in each hip (n = 5) or
      with 3 mL of the same vector preparation/hip (n = 1). In addition, one 3-month
      old sheep was injected unilaterally with 1 mL of the same vector preparation.
      Blood and marrow of these animals were analyzed for the transgene before
      injection and at intervals thereafter. At 1 week postinjection, an average of
      11.6% of the lymphocytes and 25.5% of the granulocytes/monocytes in the marrow,
      and an average of 0.9% of the lymphocytes and 1.8% of the granulocytes/monocytes
      in the blood contained and expressed the LacZ gene. The presence/expression of
      the transgene has persisted for at least 13 months within the blood and bone
      marrow of these animals. These findings demonstrate that the direct injection of
      small volumes of high-titer retroviral supernatant into the bone marrow of
      newborn sheep results in transduction of hematopoietic cells that persists for at
      least 13 months postinjection.

PMID- 10880751
TI  - Self-renewal and differentiation of a novel bipotent myeloid progenitor clone in
      the stroma-dependent culture.
AB  - To understand regulation of myeloid development, it is necessary to obtain the
      myeloid progenitor cell lines with self-renewal and differentiation capacities.
      Because prolonged hematopoiesis occurs with the production of myeloid cells at
      all stages of differentiation in the Dexter-type long-term bone marrow cultures,
      we tried to obtain stroma-dependent myeloid progenitor cells starting from the
      long-term bone marrow culture. Murine cobblestone areas generated in long-term
      bone marrow cultures were serially passaged every 10 days. After 4 months, the
      resultant hematopoietic cells, designated as DFC, were passaged on a monolayer of
      established spleen stromal cell line, MSS62. After 10-12 passages of DFC cells on
      MSS62, several clones were obtained by colony formation on MSS62 cell layer.
      Among these clones, DFC-a cells could be maintained for a long period by
      coculturing with the established stromal cell line, MSS62.DFC-a cells
      proliferated by forming cobblestones and contained blast cells, granulocytes, and
      macrophages. Cell sorting and coculture experiments indicated that the blast type
      cells exhibiting c-Kit(+) Gr-1(-) Mac-1(-), stroma-dependently self-renewed, and
      spontaneously differentiated toward granulocytes (c-Kit(+) Gr-1(+) Mac-1(+)) and
      macrophages (c-Kit(low/+) Gr-1(-) Mac-1(high)). Although most of DFC-a cells
      expressed c-Kit, SCF-c-Kit interaction was not always necessary for their growth.
      In the presence of stromal cells, growth and differentiation of DFC-a cells were
      stimulated by GM-CSF or IL-3. Without stromal cells, DFC-a was transiently
      expanded by GM-CSF or IL-3 but could not be maintained constantly by these
      cytokines. The present study demonstrated that DFC-a is a novel bipotent myeloid
      progenitor cell clone as a simple model system of stroma-dependent myeloid
      development. It may reflect distinct properties for the earliest myeloid
      progenitor cells in vivo. It is of interest to know what signals are provided by
      MSS62 stromal cells to maintain the myeloid progenitor cells.

PMID- 10880752
TI  - Primitive acute myeloid leukemia cells with long-term proliferative ability in
      vitro and in vivo lack surface expression of c-kit (CD117).
AB  - A hierarchy of progenitor cells is thought to exist in human acute myeloid
      leukemia (AML), with only the most primitive cells capable of proliferating to
      maintain the malignant clone. To further characterize this AML cell hierarchy, we
      evaluated the coexpression of CD34 and c-kit (CD117) on cells that are capable of
      long-term proliferation in vitro and in vivo.AML cells were sorted for
      coexpression of CD34 and c-kit (CD117) using two c-kit monoclonal antibodies
      (mAbs), clones 95C3 and 104D2. Sorted subfractions were evaluated for the ability
      to produce colony-forming units (CFU) for up to 8 weeks in suspension culture
      (SC) and for the capacity to repopulate NOD/SCID mice. When expression of c-kit
      on blood cells from 19 AML patients at diagnosis was compared using both mAbs,
      expression defined by 104D2 (34% +/- 6% c-kit(+)) was somewhat higher than that
      defined using 95C3 (18% +/- 4%). AML cells were sorted for coexpression of CD34
      and c-kit using both c-kit mAbs, and the subfractions were assayed in vitro and
      in vivo. Whereas the majority of AML blast cells lacked expression of CD34, most
      AML cells capable of proliferating to produce CFU after 4 to 8 weeks in SC were
      CD34(+)/c-kit(-). Cultures of sorted CD34(+)/c-kit(-) cells, supplemented with
      steel factor, were composed of a large proportion (18% to 87%) of CD34(+)/c
      kit(+) cells after 1 week, suggesting that either c-kit expression was
      upregulated or CD34(+)/c-kit(+) cells were produced. Moreover, the CD34(+)/c-kit(
      ) subfraction was found to be capable of responding to steel factor alone to
      produce CFU after 4 weeks in SC. In most AML patients tested (11/15), the only
      sorted subfraction capable of engrafting NOD/SCID mice was CD34(+)/c-kit(-). The
      CD34(+)/c-kit(+) subfraction from only 2 of the 15 patients and CD34(-) cells
      from 3 patients also engrafted the NOD/SCIDs. Only the CD34(+)/c-kit(+)
      subfraction of normal bone marrow engrafted. These studies suggest that primitive
      AML cells capable of long-term proliferation in vitro and NOD/SCID repopulation
      differ from primitive normal progenitor cells in their lack of surface expression
      of c-kit.

PMID- 10880753
TI  - Ganglioside GD1a enhances immunoglobulin production by human peripheral blood
      mononuclear cells.
AB  - We previously reported that ganglioside GD1a greatly enhanced spontaneous
      immunoglobulin (Ig) production by human peripheral blood mononuclear cells (PBMC)
      in vitro. We herein examined the mechanism for the stimulatory effect of
      GD1a.PBMC from healthy volunteers were cultured with GD1a. The amounts of IgG,
      IgM, and IgA and cytokine activity in the culture supernatants were measured by
      enzyme-linked immunosorbent assays. Proliferation was determined by [3H]
      thymidine uptake.GD1a at 10(-6) M increased IgG, IgM, and IgA production by PBMC
      2.10-fold, 2.10-fold, and 2.23-fold above the control values, respectively. GD1a
      did not affect the proliferation and viability of PBMC. GD1a did not alter Ig
      production of B cells alone. Anti-interleukin-6 (IL-6) or anti-IL-10 antibody
      each partially blocked the GD1a-induced enhancement of Ig production by PBMC, and
      the addition of both antibodies completely blocked the enhancement. GD1a
      increased IL-6 and IL-10 production of monocytes without altering those of T
      cells or B cells. The supernatant from GD1a-treated monocytes enhanced B cell Ig
      production to a greater extent than that from medium-treated monocytes. The
      supernatant-mediated effect of GD1a was partially blocked by anti-IL-6 or anti-IL
      10 antibody, and the addition of both antibodies completely blocked the GD1a
      effect. GD1a-induced increases of IL-6 and IL-10 production in monocytes were
      both blocked by Ca(2)+/calmodulin (CaM)-dependent phosphodiesterase (PDE)
      inhibitors, 8-methoxymethyl-3-isobutyl-1-methylxanthine and vinpocetin, but not
      by other signal-transducing enzyme inhibitors. The culture with GD1a enhanced
      Ca(2)+/CaM-dependent PDE activity in monocytes. These results suggest that GD1a
      may indirectly enhance B cell Ig production in whole PBMC by increasing IL-6 and
      IL-10 production of monocytes via promoting Ca(2)+/CaM-dependent PDE activity.

PMID- 10880754
TI  - Effect of the irradiated microenvironment on the expression and
      retrotransposition of intracisternal type A particles in hematopoietic cells.
AB  - We have previously demonstrated that the frequency of transformation of the
      factor-dependent hematopoietic cell line FDCP-1JL26 was dramatically increased
      when cells were cocultured with the irradiated bone marrow cell line D2XRII. In
      many of our factor-independent subclonal cell lines that we examined,
      transformation to factor independence appeared to be due to the
      retrotransposition of intracisternal type A particles (IAP) into the growth
      factor genes that are normally required for survival and growth of FDCP-1JL26
      cells. To determine the role of the irradiated microenvironment in the evolution
      of factor-independent cells, we have examined the expression and
      retrotransposition of IAPs after exposure to the irradiated bone marrow stromal
      cell line D2XRII. Differential display and Northern blot analysis demonstrated
      that IAPs were overexpressed in a nonautocrine factor-independent subclonal cell
      line, FI7CL2. The frequency of retrotransposition was determined by the
      introduction of the IAP-neo(RT) plasmid into FDCP-1JL26 cells. The IAP-neo(RT)
      contains a neomycin resistance gene (neo) that only becomes active after
      retrotransposition, and thus the frequency of retrotransposition in FDCP-1JL26
      cells was quantified by determining the frequency of neo-resistant cells.No
      significant increases in the expression of IAPs were observed after the cells
      were exposed to the irradiated stromal cells. This observation is in agreement
      with the observation that no increase in the frequency of retrotransposition
      could be detected. These results suggest that the irradiated bone marrow may have
      a passive role in the selection of factor-independent cells. During
      cocultivation, bone marrow stromal cells may provide a factor(s) to hematopoietic
      cells that allow it to survive in medium lacking IL-3. At random, a
      retrotransposition may occur that provides a selective advantage to the
      hematopoietic cells. In the absence of the irradiated stromal cells, the
      hematopoietic cells are perhaps more likely to die and therefore are not
      available for a random retrotransposition event to occur. This model is to be
      distinguished from an active role in which the irradiated microenvironment would
      synthesize or activate a factor(s) that promotes retrotransposition.

PMID- 10880755
TI  - Extensive generation of human cord blood CD34(+) stem cells from Lin(-)CD34(-)
      cells in a long-term in vitro system.
AB  - Human CD34(-) hematopoietic stem cells (HSCs) have been identified as potential
      precursors of CD34(+) HSCs by using xenogeneic transplantation systems. However,
      the properties of CD34(+) cells generated from CD34(-) cells have not been
      precisely analyzed due to the lack of an in vitro system in which CD34(+) cells
      are continuously produced from CD34(-) cells. We conducted this study to
      determine whether CD34(+) cells generated in vitro from CD34(-) cells have long
      term multilineage reconstitution abilities. Lin(-)CD34(-) population isolated
      from human cord blood was cultured in the presence of murine bone marrow stroma
      cell line, HESS-5, and human cytokines, thrombopoietin, Flk2/Flt3 ligand, stem
      cell factor, granulocyte colony-stimulating factor, interleukin 3 (IL-3), and IL
      6. They were analyzed weekly for their surface markers expressions, colony
      forming cells, long-term culture initiating cells (LTC-IC), and SCID repopulating
      cells (SRC) abilities up to 30 days of culture. In this culture system, more than
      10(7) CD34(+) cells can be continuously generated from 10(4) CD34(-) cells over
      30 days. These CD34(+) cells produce colony-forming units, LTC-IC, and SRC with
      multi-lineage differentiation, all of which are characteristic features of
      hematopoietic stem/progenitor cells. These findings suggest that CD34(-) HSCs
      have extensive potential for the generation of CD34(+) HSCs in vitro. This system
      provides a novel and potentially useful procedure to generate CD34(+) cells for
      clinical transplantation and gene therapy.

PMID- 10880756
TI  - Expression and secretion of vascular endothelial growth factor-A by cytokine
      stimulated hematopoietic progenitor cells. Possible role in the hematopoietic
      microenvironment.
AB  - In the hematopoietic microenvironment, bone marrow endothelial cells may play an
      important role in trafficking and maintenance of progenitor and stem cells due to
      adhesive interactions and paracrine secretion of hematopoietic growth factors.
      However, it is unknown whether progenitors in turn modulate endothelial
      proliferation and function. We analyzed mRNA expression (Northern blot) and
      release of vascular endothelial growth factor-A (VEGF-A), which specifically acts
      on endothelial cells, by cytokine-stimulated peripheral blood-derived CD34+
      hematopoietic progenitor cells. While unstimulated CD34+ cells expressed VEGF-A
      mRNA weakly without cytokine release in vitro, incubation for 24 hours with a
      single cytokine (e.g., kit ligand [KL]) resulted in increased VEGF-A mRNA
      expression and significant secretion of VEGF-A into the supernatant. The amount
      of VEGF released was substantially augmented by incubation with a combination of
      cytokines (e.g., KL, IL-3, GM-CSF, G-CSF), or by exposure to hematopoietic
      cytokines for a longer time period. In addition, we show that VEGF induced the
      release of hematopoietic growth factors (GM-CSF) by bone marrow endothelial cells
      and that in vitro stromal cell-derived factor-1 (SDF-1) driven transendothelial
      progenitor cell migration was increased by the presence of VEGF, which might be
      due to pore formation (increased endothelial fenestration). In vivo, release of
      VEGF by progenitor cells may result in a paracrine loop supporting proliferation
      of both endothelium and progenitors and may facilitate transendothelial migration
      during cytokine-induced progenitor cell mobilization.

PMID- 10880757
TI  - Proliferation kinetics and differentiation potential of ex vivo expanded human
      bone marrow stromal cells: Implications for their use in cell therapy.
AB  - Bone marrow stromal cells (BMSC) are an attractive target for novel strategies in
      the gene/cell therapy of hematologic and skeletal pathologies, involving BMSC in
      vitro expansion/transfection and reinfusion. We investigated the effects of in
      vitro expansion on BMSC pluripotentiality, proliferative ability, and bone
      forming efficiency in vivo. BMSC from three marrow donors were cultured to
      determine their growth kinetics. At each passage, their differentiation potential
      was verified by culture in inductive media and staining with alizarin red, alcian
      blue, or Sudan black, and by immunostaining for osteocalcin or collagen II. First
      passage cells were compared to fresh marrow for their bone-forming efficiency in
      vivo. Stromal cell clones were isolated from five donors and characterized for
      their multidifferentiation ability. The lifespan and differentiation kinetics of
      five of these clones were determined. After the first passage, BMSC had a
      markedly diminish proliferation rate and gradually lost their multiple
      differentiation potential. Their bone-forming efficiency in vivo was reduced by
      about 36 times at first confluence as compared to fresh bone marrow. Experiments
      on the clones yielded comparable results. Culture expansion causes BMSC to
      gradually lose their early progenitor properties. Both the duration and the
      conditions of culture could be crucial to successful clinical use of these cells
      and must be considered when designing novel therapeutic strategies involving
      stromal mesenchymal progenitor manipulation and reinfusion.

PMID- 10880758
TI  - ETK2 receptor tyrosine kinase promotes survival of factor-dependent FDC-P1
      progenitor cells.
AB  - By virtue of its high expression in both developing hematopoietic tissues and
      many myeloid leukemia cells lines, the embryonic tyrosine kinase receptor ETK2
      (also known as Tyro3, Sky, and Rse) has been postulated to play a role in early
      hematopoiesis. To investigate this role, we expressed murine ETK2 in the
      interleukin 3 (IL-3) dependent myeloid progenitor cell line FDC-P1 and examined
      its effect on growth factor dependence.ETK2 cDNAs encoding full-length or kinase
      domain-deleted receptor were retrovirally transduced into murine FDC-P1 cells.
      Survival, cell cycle status, and proliferative responses of ETK2 expressing
      clones were studied at normal and reduced growth factor concentrations. ETK2 was
      expressed as a functional tyrosine kinase of 110 and 150 kDa. This proto-oncogene
      altered the growth of FDC-P1 cells, allowing survival at reduced growth factor
      concentrations and delaying apoptosis after IL-3 withdrawal. ETK2-expressing
      clones contained a higher fraction of cells in the S/G2/M phases of the cell
      cycle, both after cytokine withdrawal and in the presence of IL-3. Furthermore,
      these cells had a modestly enhanced proliferative response to IL-3 and
      granulocyte-macrophage colony-stimulating factor, suggesting that ETK2
      intracellular signaling may converge with that of hematopoietic growth factors.
      The effects of ETK2 expression on viability and proliferation were largely
      dependent on a functional intracellular tyrosine kinase domain. These results
      support a role for ETK2 in the survival and/or expansion of primitive
      hematopoietic cells and suggest that this tyrosine kinase may be implicated in
      myeloid leukemogenesis as well.

PMID- 10880759
TI  - The plant lectin FRIL supports prolonged in vitro maintenance of quiescent human
      cord blood CD34(+)CD38(-/low)/SCID repopulating stem cells.
AB  - Ex vivo maintenance of human stem cells is crucial for many clinical
      applications. Current culture methods rely on optimized combinations of
      cytokines. Although these conditions provide some level of stem cell support,
      they primarily induce proliferation and differentiation, resulting in reduced
      repopulation capacity. The recently identified legume lectin FRIL has been shown
      to preserve human cord blood progenitors up to a month in suspension culture
      without medium changes. To test whether FRIL also preserves human SCID
      repopulating stem cells (SRC), we cultured human CD34(+) cord blood cells in
      medium containing FRIL, with or without subsequent exposure to cytokines, and
      tested their repopulating potential. We report that FRIL maintains SRC between 6
      and 13 days in culture. Incubation of CD34(+) cells with FRIL results in
      significantly lower numbers of cycling cells compared with cytokine-stimulated
      cells. CD34(+) cells first cultured with FRIL for 6 days and subsequently exposed
      to cytokines for an additional 4 days generated significantly more mononuclear
      and progenitor cells and higher levels of engraftment in NOD/SCID mice compared
      with CD34(+) cells cultured with FRIL alone. Similar results were obtained with
      CD34(+)CD38(-/low) cells, including expansion of SRC that were cultured in FRIL
      followed by cytokine stimulation. Moreover, CD34(+) cells precultured with FRIL
      successfully engrafted primary and more importantly secondary recipients with
      lymphoid and myeloid cells, providing further support that FRIL maintains SRC for
      prolonged periods.FRIL's ability to preserve quiescent primitive cells in a
      reversible manner may significantly expand the time and range of ex vivo
      manipulations of human stem cells for clinical applications.

PMID- 10880760
TI  - Dietary ortho phenols that induce glutathione S-transferase and increase the
      resistance of cells to hydrogen peroxide are potential cancer chemopreventives
      that act by two mechanisms: the alleviation of oxidative stress and the
      detoxification of mutagenic xenobiotics.
AB  - Oxidative stress is implicated in the etiology of cancer, hence compounds that
      alleviate oxidative stress by inducing enzymes that defend against free radical
      damage might be useful as cancer chemopreventives. Glutathione S-transferase
      (GST) has been suggested to be a candidate for a critical enzyme in protecting
      cells against free radical damage, in part, because its level of induction
      correlates with protection of the cell line IMR-32 against hydrogen peroxide
      induced oxidative stress. The present study identified dietary ortho phenols that
      both induce GST and protect the cell line IMR-32 against hydrogen peroxide-caused
      oxidative stress. The ortho phenol (o-phenol) inducers were better protectors
      against oxidative stress than a number of GST inducers that did not bear phenolic
      groups, possibly because the phenol residues of the ortho phenols allowed their
      action as antioxidants as well as inducers of GST. GST has previously been
      thought to protect cells against cancer by detoxifying mutagenic xenobiotics. The
      present results suggest that ortho phenol inducers of GST might be useful as
      cancer chemopreventives that act by two independent mechanisms, the alleviation
      of oxidative stress and the detoxification of mutagenic xenobiotics.

PMID- 10880761
TI  - Location-dependent role of the human glioma cell peripheral-type benzodiazepine
      receptor in proliferation and steroid biosynthesis.
AB  - We examined the localization and function of the peripheral-type benzodiazepine
      receptor (PBR), a protein highly expressed in steroidogenic tissues and
      aggressive tumor cells, in cell lines derived from glioblastoma multiforme
      tumors. In MGM-1 cells, PBR is located in the nucleus, and cells proliferate in
      response to PBR ligands but do not synthesize steroids de novo. In MGM-3 cells,
      PBR is located in mitochondria and the cells synthesize steroids, but do not
      proliferate in response to PBR ligands. In glioblastoma biopsies, PBR is
      expressed in the nuclei of cells, while it is found in the cytosol of
      astrocytomas, and is absent from meningioma and medulloblastoma tumor biopsies.
      These data suggest that the subcellular localization of PBR defines its function.

PMID- 10880762
TI  - 2-Amino-3-methylimidazo[4,5-f]quinoline inhibits nitric oxide production in
      lipopolysaccharide-stimulated RAW 264.7 cells by blocking p38 kinase activation.
AB  - We show that 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), a heterocyclic amine,
      significantly inhibits nitric oxide (NO) production in lipopolysaccharide (LPS)
      stimulated macrophages. The decrease in NO production was found to correlate well
      with a decrease in inducible NO synthase (iNOS) mRNA expression as demonstrated
      by Northern blot analysis. Treatment of RAW 264.7 cells with IQ selectively
      inhibited the activation of NF-kappaB/Rel, an important transcription factor of
      iNOS gene expression, while neither AP-1 nor Oct was affected by IQ. Since iNOS
      transcription has been shown recently to be under the control of the p38 kinase
      signaling cascade, we assessed the effect of IQ on p38 kinase activation.
      Treatment of RAW 264.7 with IQ inhibited LPS-stimulated p38 kinase
      phosphorylation in a dose-related manner. IQ also inhibited the p38 kinase
      activity. Collectively, this series of experiments indicates that IQ inhibits LPS
      induced expression of iNOS gene in RAW 264.7 cells. Based on our findings, the
      most likely mechanism that can account for this biological effect involves the
      negative regulation of NF-kappaB/Rel and p38 kinase pathway.

PMID- 10880763
TI  - Quantitative comparison of alpha-fetoprotein and albumin mRNA levels in
      hepatocellular carcinoma/adenoma, non-tumor liver and blood: implications in
      cancer detection and monitoring.
AB  - Early detection of recurrence is valuable for monitoring hepatocellular carcinoma
      (HCC) progression. By quantitative reverse transcriptase polymerase chain
      reaction (RT-PCR), we derived calibration curves for alpha-fetoprotein (afp) and
      albumin (alb) mRNAs using 40 matched tumors and non-tumor liver tissues from
      HCC/adenoma patients. We prospectively quantified tumor cells and non-tumor liver
      cells in 62 patients' blood samples before, during and after surgery. Expression
      of both mRNAs was heterogeneous (1-10(5)-fold) between tumors and HepG2 cell
      line. The alb-mRNA levels in non-tumor liver cells were 2-10-fold higher than in
      tumor cells. The afp-mRNA levels in HCC cells were 30-1000-fold higher than in
      non-tumor cells. The alb-mRNA level in blood may reflect the number of liver
      cells, whereas the afp-mRNA level may represent mostly the number of HCC cells.
      We found different ratios of circulating HCC cells to non-tumor liver cells
      during the clinical course of patients, in association with the subsequent
      development of recurrence/metastasis. This approach may prove useful for
      detecting and monitoring HCC progression.

PMID- 10880764
TI  - Transduction of the human deoxycytidine kinase gene in rodent tumor cells induces
      in vivo growth retardation in syngeneic hosts.
AB  - Deoxycytidine kinase (dCK) mediates the phosphorylation of nucleoside analogues
      that can be used as anti-cancer agents. We examined whether susceptibility of
      mouse colon carcinoma (Colon 26) and rat gliosarcoma (9L) cells to 1-beta-D
      arabiofuranosylcytonsine (AraC), a chemotherapeutic agent, can be increased after
      the tumor cells were transduced with the human dCK gene. Expression of the dCK
      gene in both cell lines conferred increased sensitivity in vitro to AraC.
      Although their proliferation rates in vitro remained the same as those of
      parental cells, tumor growth of the transduced cells in syngeneic host animals
      was unexpectedly retarded compared with that of respective parental cells. In
      contrast, the growth of the transduced cells was not different from that of
      parental cells, when they were inoculated in T cell-defective nude mice. A
      histological examination revealed infiltration of eosinophils into the dCK gene
      transduced but not into parental Colon 26 tumor. These data suggest that a
      therapeutic gene, when expressed in xenogenic animals, can be a tumor antigen
      which is recognized by a host defense system.

PMID- 10880765
TI  - Enhanced oncogenicity of human papillomavirus type 16 (HPV16) variants in
      Japanese population.
AB  - To investigate whether HPV16 E6 variants carry an elevated risk for cervical
      cancer in Japanese population, we investigated the E6 sequence variation in 40
      cervical intraepithelial neoplasias (CINs) I-III and 43 invasive cervical cancers
      (ICCs), all positive for HPV16. HPV16 E6 variants were frequently found in ICCs
      than in CINs (88 vs. 65%, P=0.01). The E6 D25E, a rare variant in Western
      countries, was most frequently observed in ICC (44%). CIN I/II lesions with HPV16
      variants were less likely to regress than those with HPV16 prototype (P=0.048).
      The finding that HPV16 E6 variants represent a significant risk factor is common
      between Western and Japanese women despite the different distribution of each
      variant.

PMID- 10880767
TI  - Possible mechanisms underlying mammary carcinogenesis in female Wistar rats by
      nitrofurazone.
AB  - Mechanisms underlying mammary carcinogenesis in female rat given nitrofurazone
      (NF) were examined. Experiment I: female Wistar rats were divided into three
      groups, and given diets containing 0, 500 or 1000 ppm NF for 5 weeks. At terminal
      sacrifice, body and uterus weights were the same in all groups, although ovary
      weights in NF-treated animals were significantly higher than in control animals,
      the increase being dose-dependent. Serum prolactin (PRL) concentrations in NF
      treated groups at 17:00 h on the day of proestrus were also dose-dependently
      higher than that in control group. Experiment II: a two-stage rat mammary
      carcinogenesis protocol was performed. Rats were divided into four groups, Groups
      2 and 4 being treated by 9,10-dimethyl-1,2-benzanthracene (DMBA) at 7-weeks-old.
      Groups 3 and 4 were given diets containing 1000 ppm of NF between 8 and 27 weeks
      of age, when all surviving rats were autopsied. DMBA-treated animals demonstrated
      mammary tumors at high incidences, 91.1 and 90.5%, respectively, in Groups 2 and
      4, no tumor development being observed without the initial carcinogen exposure
      (Groups 1 and 3). The mean tumor weights and the mean numbers of tumors per tumor
      bearing rats in Group 4 were increased as compared with Group 2, albeit not
      significantly. Serum PRL (proestrus day at 17:00 h) and progesterone (PG)
      (diestrus day at 10:00 h) concentrations in NF-treated animals (Groups 3 and 4)
      were significantly higher than those in untreated rats (Groups 1 and 2). These
      results suggest that increases of serum PRL and PG concentrations by NF may be
      the most important factors regarding its promotion of mammary tumor growth and/or
      enhancement of mammary carcinogenesis in female rats.

PMID- 10880766
TI  - Expression of hGSTP1 alleles in human lung and catalytic activity of the native
      protein variants towards 1-chloro-2,4-dinitrobenzene, 4-vinylpyridine and (+)
      anti benzo[a]pyrene-7,8-diol-9,10-oxide.
AB  - The human glutathione S-transferase (GST) P1 alleles coding for Val(105)
      (hGSTP1*B and/or P1*C) are over- represented in lung cancer patients. However,
      the corresponding recombinant Val(105) protein variants tend to show higher
      catalytic activity than the Ile(105) variants towards bay-region diol epoxides
      that are thought to be etiological agents in lung cancer. We have examined 29
      normal human lung samples with respect to several factors that could confound
      relationships between hGSTP1 allele type and cancer susceptibility, namely, inter
      individual and allele-specific variation of hGSTP1 expression, and differences
      between the catalytic properties of the native and recombinant hGSTP1-1 variant
      protein products. hGSTP1 expression varied 7-fold among individuals but was
      independent of hGSTP1*A, P1*B or P1*C allele type. hGST subunits A1, A2, M1 and
      M3 were minor components, similarly variable in expression. Despite this
      variability of expression, the levels of hGSTP1 expression linearly correlated
      with those of the next most highly expressed GST, hGSTM3, even though the genes
      for these GSTs are on different chromosomes. Differences between the native
      protein variants, using 1-chloro-2,4-dinitrobenzene and (+)-anti-benzo[a]pyrene
      diolepoxide as substrates, were more marked than those between the recombinant
      variants. However, the order of differential catalytic specificity was the same
      for native and recombinant variants. Neither the expression of the hGSTP1 alleles
      nor the catalytic properties of the protein variants appears to provide a simple
      mechanistic rationale for the observed over-representation of the hGSTP1*B and/or
      1*C alleles in lung cancer.

PMID- 10880768
TI  - Expression of translationally controlled tumor protein mRNA in human colon
      cancer.
AB  - The translationally controlled tumor protein (TCTP) was first identified as a
      tumor-associated protein. Here we described the expression profile of TCTP mRNA
      using a panel of normal human tissues. We also investigated the cell-cycle
      dependent expression of the TCTP mRNA using synchronized cultures of
      Saccahromyces cerevisiae. The TCTP gene was constantly expressed through the
      yeast cell cycle. The expression of TCTP mRNA from three human colon carcinoma
      cell lines and their tumors xenografted in a nude mouse was studied. Our data
      imply that the TCTP is a housekeeping gene and that its deregulation may be
      involved in the tumor development of colon carcinoma.

PMID- 10880769
TI  - The identification of novel therapeutic targets for the treatment of malignant
      brain tumors.
AB  - A two-step strategy was developed consisting of differential display reverse
      transcriptase polymerase chain reaction (DDRT-PCR) with cultured normal human
      fetal astrocytes and U-373MG glioma cells followed by reverse Northern analysis
      of normal brain and primary tumor tissues. hu-dek, alpha-NAC, ribosomal proteins
      L7a and L35a, and five novel genes were identified. Since none of these genes has
      been previously shown to be associated with malignant brain tumor formation, this
      approach may be useful to identify novel targets for the diagnosis and treatment
      of brain tumors.

PMID- 10880770
TI  - Inhibitory effect of melatonin on 7, 12-dimethylbenz[a]anthracene-induced
      carcinogenesis of the uterine cervix and vagina in mice and mutagenesis in vitro.
AB  - Forty female CBA mice aged 3-4 months were exposed twice a week during 2 months
      to intravaginal applications of polyurethane sponges impregnated with 0.1%
      solution of 7,12-dimethylbenz[a]anthracene (DMBA) in triethyleneglycol. Three
      hours after each application the sponges were taken out. Starting from the day of
      the 1st DMBA application a part of mice was exposed five times a week during 4
      months with melatonin in tap water (20 mg/l) given at night time (from 18:00 to
      09:00 h). Additional 20 female CBA mice were intact and served as a control. All
      mice were sacrificed in 6 months after start of the experiment. Seven of 20 mice
      exposed to DMBA alone developed malignancies in the vagina and cervix uteri and
      two mice developed benign cervical tumors. No malignancies in vagina and uterine
      cervix and three vaginal papillomas were observed in mice exposed to
      DMBA+melatonin. There were no any tumors in intact controls. Two in vitro tests
      were used for mutagenicity studies: the Ames test (strains TA 97 and TA 98 of
      Salmonella typhimurium) and the single cell gel electrophoresis assay (SCGE assay
      or COMET assay) performed on CHOK1 cells. In tested strains melatonin
      significantly reduced the mutagenicity of DMBA. In the SCGE assay preincubation
      with melatonin led to a strong inhibition of clastogenic activities of DMBA.
      Thus, our data indicate that pineal indole hormone melatonin inhibits cervical
      and vaginal carcinogenesis induced by DMBA in mice and possess antimutagenic and
      anticlastogenic effect in vitro.

PMID- 10880771
TI  - Loss of heterozygosity and microsatellite instability in ductal carcinoma in situ
      of the breast.
AB  - To investigate the alterations of genetic instabilities in carcinogenesis of the
      breast, we analyzed the allelotypic profile of 65 ductal carcinomas in situ
      (DCIS), compared with that of 207 invasive ductal carcinomas (IDC) of the breast.
      These studies were performed by means of examining microsatellite-length
      polymorphisms at seven loci (AluVpa, ESR, D11S988, D13S267, D16S398, D17S1159,
      and D17S855) from microdissected paraffin sections. Allelic loss or imbalance,
      considered a loss of heterozygosity (LOH), tended to be more frequently seen in
      IDC than in DCIS. In particular, the frequency of LOH at the 17p locus was
      significantly higher in IDC than in DCIS (42 vs. 23%, P=0.022). LOH in DCIS was
      most frequently seen at D16S398 (26%). LOH frequency at D16S398 in low- and
      intermediate-grade DCIS was higher than that in high-grade DCIS, while LOH
      frequencies at D11S988 and D17S1159 in low- and intermediate-grade DCIS was lower
      than those in high-grade DCIS. LOH frequency at D11S988 in non-comedo type DCIS
      was lower than that in comedo type DCIS. Furthermore, the frequency of
      microsatellite instability (MSI) at only one locus in DCIS (28%) was
      statistically higher than that in IDC (6%) (P<0.001), while there was no
      difference between the frequency of MSI at multiple loci in DCIS (6%) and that in
      IDC (3%). Together, these observations indicate that chromosomal losses of 16q
      may occur in low- and intermediate-grade DCIS and those of 11p and 17p may occur
      high-grade DCIS, and that MSI occurring at only one locus is not yet clear and
      MSI at multiple loci is uncommon in not only IDC but also DCIS of the breast.

PMID- 10880772
TI  - Evaluating the outcome of treatment. Shouldn't We be asking patients if they are
      better?
AB  - Increasingly clinicians and investigators are recognizing the need to include
      patients in the assessment of therapy. Patient-based assessments, such as
      measures of health status or health-related quality-of-life, require patients to
      rate themselves on a fixed number of questions. Because patients come to their
      doctors with unique, different, and individual concerns, the concern is that
      commonly used scales with a fixed number of questions might be excluding
      important individual concerns or including issues irrelevant to individual
      patients. Clinicians usually do not rely on health status questionnaires in
      routine practice to judge the success of therapy, but ask patients directly if
      they are better. Despite this fundamental interchange between patients and
      clinicians, relatively little attention has been directed towards the
      specification, measurement, and quantification of patients' individual concerns.
      Patient-specific measures are a particular type of measure which allow patients
      to state their individual concerns, and weight their relative importance. Because
      we are often trying to address with treatment the concerns of individual
      patients, patient-specific outcomes would provide us a standardized method useful
      in research and clinical practice of asking patients whether they are better.

PMID- 10880773
TI  - The health and activities limitation index in patients with acute myocardial
      infarction.
AB  - Utility assessment is required to estimate quality-adjusted life years, but is
      often avoided due to the cumbersome nature of elicitation techniques. The Health
      Activities and Limitations Index (HALex) offers a method of utility assessment
      using existing values from the National Health Interview Survey (NHIS) and a
      utility algorithm to derive preferences. The authors assessed the construct
      validity of the HALex by comparing derived values with directly assessed HALex
      utilities in patients post acute myocardial infarction (AMI). OLS regression was
      used to model the relationship between utilities and patient demographics,
      comorbidities, and treatment. The mean and median utility for patients (n = 160)
      was.57 (SD = 22) and.55 respectively, and was not statistically different from
      the mean [.57 (SD =.30)] and median (.58) for similar NHIS respondents (n = 46).
      Patients with a comorbidity index of three or less had mean utilities.13 higher
      than the mean utility for patients with an index of four or more. No relationship
      was found between patients' age, race, and income and their utilities. The HALex
      scoring algorithm is a promising means to obtain utilities, and provides a
      methodology to easily estimate utilities for patients, but is not without
      limitations.

PMID- 10880774
TI  - Evolution of self-rated health status in the elderly: cross-sectional vs.
      longitudinal estimates.
AB  - We assessed the perceived health status evolution among elderly subjects and
      examined the age-related differences in perceived health when comparing estimates
      obtained from cross-sectional and longitudinal approaches. Data come from a
      cohort of non-institutionalized individuals aged 65 years or older, living in
      Barcelona, Spain. One thousand three hundred fifteen (1315) elderly were
      successfully interviewed at baseline in 1986 and 754 (84.6% of the eligible) at
      the re-assessment (1993-1994). Estimates of change in perceived health status
      were calculated based on cross-sectional and longitudinal approaches. Cross
      sectionally, no significant differences in the proportion of individuals with
      poor self-rated health were found (40.5 vs. 42.5%, P = 0.90). Among survivors,
      the proportion of individuals with poor health increased from 37.8% to 55.1% (P <
      0.01), an 8.7-fold decline of perceived health when compared with the cross
      sectional estimates. Comorbidity (aOR 2.1; 95%CI: 1.4-3.3) and no education (aOR
      1.9; 95%CI: 1.1-3.2) were associated with a decline in health status after
      adjusting by baseline health status. We recommend the use of longitudinal studies
      to understand the evolution of perceived health in the elderly.

PMID- 10880775
TI  - Strategies for improving comorbidity measures based on Medicare and Medicaid
      claims data.
AB  - Claims-based measures of comorbid illness severity have generally relied on the
      diagnoses listed for a single hospitalization. Unfortunately, such diagnostic
      information is often limited because patients have not been hospitalized during
      periods of interest, because of incomplete coding of diagnoses on claims forms,
      or because listed diagnoses represent complications of the hospitalization rather
      than pre-existing comorbid conditions. To address these limitations, we developed
      and tested four comorbidity index scores for patients with breast cancer, each
      based on different sources of health services claims from Medicare and Medicaid:
      hospitalization for breast cancer surgery; outpatient care prior to the
      hospitalization; other inpatient care prior to the hospitalization; and all
      sources combined. Varying the number and type of sources of diagnostic
      information yielded only very small improvements in the prediction of mortality
      at 1 and 3 years. Surprisingly, even simpler measures of comorbidity (crude
      number of diagnoses) and of prior health care utilization (total days spent in
      the hospital) performed at least as well in predicting mortality as did the more
      complex index scores which assigned points and weights for specific conditions.
      The greatest improvement in explanatory power was observed when another source of
      clinical information (cancer stage derived from a population-based cancer
      registry) was used to supplement claims information. Expanding the source of
      claims diagnoses and focusing on time periods prior to an index hospitalization
      are insufficient for substantially improving the explanatory power of claims
      based comorbidity indices. Other improvements suggested by our results should
      include: increasing the completeness and accuracy of claims diagnoses;
      supplementing diagnoses with health care utilization information in claims data;
      and supplementing claims data with other sources of clinical information.

PMID- 10880776
TI  - Nutrition risk factors for institutionalization in a free-living functionally
      dependent elderly population.
AB  - Risk factors for institutionalization of frail elderly have been studied but the
      role of nutritional status has not been addressed. A prospective cohort of 288
      frail elderly (81 male; 207 female; mean age: 78.2 +/- 7.6 years) were recruited
      from the current list of those receiving home help services and followed for 3-5
      years. At baseline, height, weight, and arm muscle circumference were measured.
      Self-reported weight loss prior to baseline, energy, and protein intake were
      recorded. Covariates included sociodemographic factors, social network variables,
      functional and health status. Cox's multivariate survival analysis was used to
      identify independent predictors of institutionalization. Over the period of
      observation, 46% of subjects were institutionalized. Univariate predictors
      included weight loss >/=5 kg, functional status, and not living alone. In
      multivariate analysis, weight loss significantly increased the likelihood of
      institutionalization [Hazard Ratio (HR) = 1.71 (95% CI: 1.08-2.73)] as did
      limited functional capacities [HR = 1.26 (95% CI: 1.02-1.55)]. Among the free
      living frail elderly, weight loss >/=5 kg is an important predictor of early
      institutionalization after controlling for social network, health, and functional
      status.

PMID- 10880777
TI  - Couple similarities for cognitive functions and psychological health.
AB  - Spouse correlations for cognitive functions and psychological state were
      investigated using data on 31 spouse pairs. Subjects were part of the
      Epidemiology of Vascular Aging (EVA) study, a longitudinal study on cognitive and
      vascular aging. Between July 1991 and June 1993, 1389 subjects aged 59 to 71
      years old were recruited, including 318 couples. Cognitive tests assessed global
      functioning, verbal fluency, attention, verbal memory, psychomotor speed, and
      logical intelligence. Depressive symptoms and anxiety levels were assessed by the
      Center for Epidemiological Studies Depression Scale and Spielberger Scale,
      respectively. Statistically significant positive spouse correlations were found
      for both psychological scales, spousal similarity being higher for depressive
      symptoms (r = 0.31, P < 0.0001) than anxiety level (r = 0.13, P = 0.04). When
      controlling for age, education level, and psychotropic drug use, these
      associations were not modified. Except for attention and psychomotor speed,
      significant positive spouse correlations, ranging from 0.18 for logical
      intelligence to 0.36 for global functioning, were observed for all cognitive
      performances. When adjusting for age, education level, and depressive symptoms,
      correlation coefficients decreased and spouse correlations remained significant
      for global assessments and verbal fluency. These results suggest that, in the
      elderly, spouse correlations are high for depressive symptoms and rather moderate
      for anxiety levels and cognitive performances.

PMID- 10880778
TI  - Utilization of screening mammography as a preventive practice prior to initiating
      a population-based breast cancer screening program.
AB  - Factors associated with the level of utilization of screening mammography as a
      preventive practice were analyzed prior to initiating a population-based breast
      cancer screening program. A questionnaire was used to collect information about
      screening mammography utilization during the last 4 years among women invited to
      enroll in the program. Sociodemographic and health factors, and health services
      utilization were studied. A screening mammography in the last 4 years had been
      performed on 59.3% of the 8867 women interviewed. The utilization of mammography
      was higher among women who were younger, had a higher education level, or had
      previous visits to a physician (P < 0.001). The variables more strongly
      associated with use of screening mammography were: visit to a gynecologist and
      performance of a pap smear. Also associated with the utilization of screening
      mammography were: personal history of breast pathology, family history of breast
      cancer, breast self-examination, and recent visit to a general practitioner. Self
      perceived health presented an inverse relation with screening mammography use (P
      < 0.001). The use of screening mammography appears to have increased in recent
      years, although inequalities persist which the breast cancer screening programs
      help to modulate. Mammographic frequency only would be deemed appropriate by the
      European guidelines in fewer than one-half of the cases.

PMID- 10880779
TI  - An approach to identifying incident breast cancer cases using Medicare claims
      data.
AB  - This study developed and evaluated a method for ascertaining a newly diagnosed
      breast cancer case using multiple sources of data from the Medicare claims
      system. Predictors of an incident case were operationally defined as codes for
      breast cancer-related diagnoses and procedures from hospital inpatient, hospital
      outpatient, and physician claims. The optimal combination of predictors was then
      determined from a logistic regression model using 1992 data from the linked SEER
      registries-Medicare claims data base and a sample of noncancer controls drawn
      from the SEER areas. While the ROC curve demonstrates that the model can produce
      levels of sensitivity and specificity above 90%, the positive predictive value is
      comparatively low (67-70%). This low predictive value is largely the result of
      the model's limitation in distinguishing recurrent and secondary malignancies
      from incident cases and possibly from the model identifying true incident cases
      not identified by SEER. Nevertheless, the logistic regression approach is a
      useful method for ascertaining incident cases because it allows for greater
      flexibility in changing the performance characteristics by selecting different
      cut-points depending on the application (e.g., high sensitivity for registry
      validation, high specificity for outcomes research). It also allows us to make
      specific adjustments to population based estimates of breast cancer incidence
      with claims.

PMID- 10880780
TI  - Patient characteristics and treatments associated with a decline in upper-body
      function following breast cancer therapy.
AB  - Breast cancer therapy is often followed by a decline in upper-body function.
      Women (303) diagnosed with stage I or II breast cancer were interviewed 5 and 21
      months after surgery and their medical records were reviewed. Women with
      cardiopulmonary comorbidity had an odds ratio for decline at the 5-month
      interview of 2.8 (95% CI 1.3-5. 7), relative to women without. Women who received
      mastectomy (OR = 2. 5; 95% CI 0.9-6.7) or breast-conserving surgery with
      radiation therapy (OR = 2.9; 95% CI 1.0-8.9) were at higher risk for decline at
      the 5-month interview than women who received only breast-conserving surgery.
      Women who had axillary dissection were more likely to report numbness or pain in
      the axilla (OR = 6.4; 95% CI 1.2-33) at the 21-month interview than women who did
      not. Clinicians should consider the functional consequences of treatment when
      discussing treatment options and postoperative care with women who have early
      stage breast cancer.

PMID- 10880781
TI  - Prevalence and relevance of thyroid dysfunction in 1922 cholesterol screening
      participants.
AB  - Controversy persists about the role of subclinical hypothyroidism in
      hypercholesterolemia. This study aimed to assess in a clinically healthy, middle
      aged population of employees the prevalence of thyroid function disorders and
      their relation to demographic variables and cardiovascular risk factors. 1922
      (former) employees were screened with follow-up of newly identified cases of
      undiagnosed (subclinical) hypothyroidism and hyperthyroidism. Thyroid stimulating
      hormone (TSH), prevalence and course of (subclinical) hypo- and hyperthyroidism
      and their relation to cardiovascular risk factors (cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides,
      smoking, systolic and diastolic blood pressure) were assessed. The prevalence of
      newly diagnosed subclinical hypothyroidism (cut-off TSH concentration: 4.0 mU/L)
      was 1.1% (17 women and 5 men) with a mean TSH concentration of 7.37 (95% CI 5.18
      9.56) mU/L. No case of overt hypothyroidism could be diagnosed. Elevated levels
      of antibodies to microsomal or thyroglobulin antigens were detected in six
      subjects with subclinical hypothyroidism (27.3%). Fifteen subjects (0.8%, 13
      women and 2 men) had TSH concentrations below 0.1 mU/L. The cardiovascular risk
      profile of subjects with mild subclinical hypothyroidism was not different from
      subjects with normal TSH levels. The prevalence of subclinical hypothyroidism was
      0.8% in normocholesterolemic (cholesterol <5.2 mmol/l) and 1.4% in
      hypercholesterolemic subjects (n.s.). One woman each with the subclinical form of
      the disease developed hypothyroidism or hyperthyroidism after 21 and 11 months of
      follow-up, respectively. Subclinical hypothyroidism and subclinical
      hyperthyroidism were rarely observed in a target group for coronary heart disease
      prevention. Mild subclinical hypothyroidism was not associated with any adverse
      cardiovascular risk profile. These results argue against indiscriminate
      measurements of TSH concentrations in clinically healthy subjects either with
      normocholesterolemia or hypercholesterolemia.

PMID- 10880782
TI  - Primary spontaneous pneumothorax in Arabs: does its frequency differ from
      elsewhere?
AB  - No data are available on primary spontaneous pneumothorax (PSP) in Arabs. Hence
      we sought to determine its characteristics in Arabs of the Al-Ahmadi Governorate
      in Kuwait. All patients over 10 years of age with pneumothorax who were admitted
      to the only free general hospital serving Ahmadi area from 1985 to 1996 were
      reviewed retrospectively. The study included all patients' medical records,
      investigations, treatment, morbidity, and mortality. Any patient with secondary
      pneumothorax was excluded. Primary spontaneous pneumothorax was rare in female
      Arabs, as they are almost never smokers. There were only two females out of total
      58 patients with an incidence of 0.3 per 100,000 per year. Its incidence in male
      Arabs was 8.8 per 100,000 per year, similar to that in other studies. The
      distribution had a monophasic pattern, the average age being 23 (+/- 7.3 SD)
      years at the first episode. Smoking, a tall, asthenic (slim, relatively weak in
      appearance, ectomorphic) body build, and a positive family history are the most
      important risk factors and are not different from most studies conducted in other
      parts of the world.

PMID- 10880783
TI  - Risk markers are not without risk.

PMID- 10880784
TI  - Reported current use of prescription drugs and some of its determinants among 35
      to 65-year-old women in mid-Sweden: A population-based study.
AB  - To investigate prescribed drug utilization in a middle-aged female population and
      factors possibly related to drug consumption in this population. A random sample
      of 4200 women aged 35-65 years, drawn from the population register of seven
      countries in mid-Sweden, received a postal questionnaire. Two thousand nine
      hundred ninety one (2991) (71.2%) women responded. Forty percent (40%) of the
      women were currently using drugs and 12% of the users were taking four drugs or
      more. Polypharmacy increased by age. A large number of factors were correlated
      with current drug use. In multivariate analyses age, perceived health, body mass
      index, and educational level remained significantly related to drug use, while
      factors such as menopausal state, smoking habits, employment status, marital
      status, and physical activity lost their significance. Current drug use among
      women increased by age, bad perceived health status, obesity, and college or
      university education.

PMID- 10880785
TI  - Use of prevalence and incidence measures to describe age-related prescribing of
      antidepressants with and without anticholinergic effects.
AB  - To evaluate whether physicians avoid prescribing highly anticholinergic
      antidepressants (AAD) in the elderly, a population-based retrospectively data
      analysis was performed using databases from a Dutch health insurance company.
      Data collected on approximately 240,000 persons covered the period from 1 July
      1993 to 1 January 1996. The prevalence and the incidence (number of new starters)
      of antidepressant use was measured over 1994 and 1995. Use of AAD was
      proportionally higher in the elderly in terms of both prevalence and incidence
      rates; the ratio of starters of AAD versus starters of non-AAD in 1994 increased
      steadily with age (from 0.54 in the age group 20-29 to 1.15 in the age group 60
      69). In 1995 these incidence ratios decreased (0.41 to 0.99, respectively);
      however, the decrease was higher in the younger age groups. The data indicate
      that in the population studied, physicians do not refrain from prescribing highly
      anticholinergic agents to older patients despite their potential adverse drug
      reactions in this age group. This study also indicates that prevalence and
      incidence rates can be extracted from reimbursement data and give insight into
      actual prescribing practices.

PMID- 10880786
TI  - Feasibility of using recipients of health promotional newsletters for post
      marketing surveillance.
AB  - Achieving an adequate sample size is one of the major difficulties in performing
      post-marketing observational studies of health outcomes in persons taking
      specific drug preparations. We assessed the feasibility of recruiting
      participants for such a study of Cardizem CD from approximately 400,000 U.S.
      recipients of a health promotion newsletter. A three-page questionnaire was sent
      to a 2.5% random sample (n = 10,000) of recipients, stratified by geographic
      region. After two mailings, 2779 (28%) returned the questionnaire. Of the 2779
      respondents, 2132 (77%) reported having high blood pressure. Eighty-seven percent
      indicated a willingness to participate in a long-term prospective study. In a
      multivariate model, calcium channel blocker (CCB) use was associated with a
      history of coronary heart disease, duration of hypertension medication use
      greater than 1 year, a rating of good or excellent hypertension care, higher
      systolic blood pressure, higher education level, family history of cardiovascular
      disease, and history of smoking. These results indicate that self-reported CCB
      users may be at greater risk of cardiovascular heart disease and that it is
      feasible to use health promotion newsletters as a source of participants in
      prospective studies of cardiovascular disease.

PMID- 10880787
TI  - Brain mapping of bilateral interactions in attention deficit hyperactivity
      disorder and control boys.
AB  - OBJECTIVES: Children with attention deficit hyperactivity disorder (ADHD) are
      thought to have deficits in attentional control, whereas the status of deficits
      at visual and pre-motor processing stages is unclear. METHODS: The timing of such
      deficits was examined with event-related potential (ERP) microstates (stimulus-
      and response-related) and continuous force recordings in 15 ADHD and 16 control
      boys in a choice reaction time task. Unilateral and bilateral stimulus and
      response conditions were used to assess bilateral interactions at visual,
      central, and pre-motor stages. RESULTS: ADHD boys showed poorer performance,
      particularly in the bilateral conditions. In the visual P1 microstates, they
      exhibited less suppression of visual evoked potential (VEP) amplitudes but
      similar speeding of VEP latencies in the bilateral compared to the summed
      unilateral condition. The central P3 and pre-/post-response microstates were
      attenuated and topographically altered in ADHD boys. The attenuation was most
      pronounced in the bilateral condition and was similar for stimulus- and response
      related averages. The lateralized readiness potential was also reduced in ADHD
      boys; this was most pronounced for the left hand responses. CONCLUSIONS: Brain
      mapping during uni- and bilateral stimulus and response conditions thus indicates
      multilevel deficits in ADHD boys affecting visuo-attentional, central, and pre
      motor processes.

PMID- 10880788
TI  - Motor cortex excitability in patients with cerebellar degeneration.
AB  - OBJECTIVES: To study motor cortex (M1) excitability and the effect of
      subthreshold transcranial magnetic stimulation (TMS) in patients with cerebellar
      degeneration and normals performing a reaction time (RT) task. METHODS: Time to
      wrist flexion after a visual go-signal was measured. TMS was always delivered at
      90% of resting motor evoked potential (MEP) threshold. In one experiment, test
      TMS was delivered at various intervals after the go-signal. In half the trials
      priming TMS was also given with the go-signal. A second experiment examined the
      effect on RT of M1 and occipital priming stimulation alone. RESULTS: M1
      excitability, measured as the likelihood of producing MEPs in the wrist flexor
      muscles, increased immediately after the go-signal in the patients and stayed
      high until movement. In controls, excitability rose gradually. This difference
      was largely eliminated by priming TMS. RT was longer in the patient group, but
      improved with priming TMS. Occipital priming produced less effect on RT than M1
      stimulation in both controls (P=0.008) and patients (P=0.0004). CONCLUSIONS: M1
      excitability prior to movement in an RT task increases abnormally early in
      cerebellar patients. This may reflect compensation for deficient thalamocortical
      drive. Subthreshold TMS can partially normalize the prolonged RT and abnormal
      excitability rise in cerebellar patients.

PMID- 10880789
TI  - Task dependence of Ia presynaptic inhibition in human wrist extensor muscles: a
      single motor unit study.
AB  - OBJECTIVE: Task-dependent changes in the Ia presynaptic inhibition generated by
      flexor group I afferents were investigated in 25 identified motor units (MUs)
      located in human extensor carpi radialis (ECR) muscles. METHODS: Seven subjects
      had to voluntarily contract their ECR muscles either alone during isometric wrist
      extension or concurrently with their wrist and finger flexor muscles while
      clenching their hand around a manipulandum. The MU reflex responses to the radial
      nerve stimulation (test stimulation) yielded narrow peaks in the post-stimulus
      time histograms (PSTH). The Ia presynaptic inhibition induced while stimulating
      the median nerve (conditioning stimulation) 20 and 40 ms before the radial nerve
      was assessed from the changes in the contents of the first 0.5 ms in the peaks.
      RESULTS: With both stimulation intervals, the Ia presynaptic inhibition, as
      assessed from the first 0.5 ms of the PSTH peaks, was consistently weaker during
      hand clenching. With both motor tasks, the Ia presynaptic inhibition was
      strongest at the 20 ms interval, in which it showed a downward gradient, working
      from slow to fast contracting MUs. With both intervals, the presynaptic
      inhibition was consistently weaker during hand clenching. The decrease in the Ia
      presynaptic inhibition observed at the 40 ms conditioning-test interval was less
      pronounced during wrist extension. CONCLUSION: It is suggested that the reason
      why Ia presynaptic inhibition was weaker during hand clenching may have been that
      this task involved numerous cutaneous inputs originating from the palm and finger
      tips. During gripping tasks, these cutaneous inputs may therefore contribute to
      adjusting the wrist stiffness by relieving the presynaptic inhibition.

PMID- 10880790
TI  - The effect of ankle joint position and effort on quadriceps reflex sensitivity.
AB  - OBJECTIVE: To investigate a possible ankle-knee synergy, experiments with normal
      subjects were performed to compare changes of the quadriceps motor pool
      excitability due to ankle position and effort. METHODS: Vastus medialis H reflex
      amplitude was examined during ankle isometric contractions conditioned by
      different ankle positions (dorsiflexion, neutral, and plantarfiexion) with or
      without voluntary effort (either in the dorsiflexion or plantarflexion
      direction). Repeated measures ANOVAs were performed on the mean and standard
      deviation of the H peak-to-peak amplitude. RESULTS: Mean vastus medialis H reflex
      amplitudes were significantly different among the trials of different ankle
      efforts (P<0.05), and significantly increased during plantarfiexion efforts. In
      contrast, mean vastus medialis H reflex amplitude did not vary with respect to
      changes of ankle position (P>0.05). CONCLUSIONS: The data suggest that (1) the
      position of the ankle joint did not significantly modify the excitability of the
      neuromotor pool of the VM muscle, in either static or active cases, and (2) the
      effort effect from the ankle joint on the VM neuromotor pool is most significant
      during ankle plantarfiexion effort. Possible mechanisms are central motor
      irradiation and peripheral force-dependent pathways from the ankle joint that
      influence the VM neuromotor pool.

PMID- 10880791
TI  - Sub-movement cueing and motor sequence execution in patients with Huntington's
      disease.
AB  - OBJECTIVES: We investigated whether the type of sub-movement cueing during the
      execution of motor sequences influences the movement time in patients with
      Huntington's disease. METHODS: The kinematic variables of rapid sequential free
      arm movements executed with different types of sub-movement cueing - externally
      triggered (ET) and self-initiated (SI) tasks - were analyzed in 7 patients and 7
      healthy controls. The ET task required subjects to initiate movements in response
      to consecutive visual go signals; the SI task allowed them to start at will.
      RESULTS: HD patients performed ET and SI tasks slower than normal subjects. Both
      groups executed ET sequences slower than SI, but movement times for the two tasks
      differed less in patients than in controls. Patients paused normally between sub
      movements during the SI task, but they had slower reaction times for all the sub
      movements of the ET task. CONCLUSIONS: Slower execution of both motor tasks
      indicates that HD patients are bradykinetic in performing sequential free arm
      movements. Our finding that total movement times for SI and ET tasks differ less
      in patients than in controls suggests that HD impairs internal more than external
      cueing mechanisms.

PMID- 10880792
TI  - Modulation of symptomatic palatal tremor by magnetic stimulation of the motor
      cortex.
AB  - OBJECTIVES: Magnetic stimulation of the motor cortex can be used to determine the
      involvement of the cortex in rhythmic movement disorders. Symptomatic palatal
      tremor (SPT) is thought to come from a pacemaker that is relatively resistant to
      internal and external stimulation. In this study, we investigated the effect of
      magnetic stimulation of motor cortex on SPT. METHODS: Five male patients, aged 67
      79 years, with SPT after brain stem infarction or hemorrhage, all had a
      synchronous mouth angle twitch with the palatal movement. Electromyographic
      activity was recorded with a monopolar needle electrode from orbicularis oris. In
      experiment 1, transcranial magnetic stimulation (TMS) was delivered at 200% motor
      threshold (MT) to reset SPT. In experiment 2, the effect of TMS intensities was
      studied at 80-240% MT in two SPT patients. To determine the influence of the TMS,
      we used the resetting index (RI). RESULTS: TMS reset the tremor in all 5 SPT
      patients at 200% MT with RIs of 0.86-0.96. The latency of the tremor reappearance
      after TMS was longer than the pre-stimulus tremor interval, and the intervals
      between the subsequent tremor bursts were also prolonged. The degree of tremor
      resetting was closely correlated with the magnetic stimulus intensity and the
      latency of the tremor reappearance after TMS. CONCLUSIONS: Stimulation of the
      motor cortex may modulate the generator of SPT.

PMID- 10880793
TI  - Effects of chronic levodopa and pergolide treatment on cortical excitability in
      patients with Parkinson's disease: a transcranial magnetic stimulation study.
AB  - OBJECTIVES: Transcranial magnetic stimulation was used to assess the effects of
      chronic levodopa and pergolide treatment on motor cortex excitability in
      Parkinson disease (PD). METHODS: Motor thresholds, intracortical inhibition and
      facilitation were studied at baseline and after 6 and 12 months of therapy in 10
      PD patients and compared to 7 age-matched controls. RESULTS: At baseline, there
      was significantly less intracortical inhibition with only a slight reduction of
      intracortical facilitation in PD as compared to controls. Relative to
      pretreatment condition, levodopa restored intracortical inhibition for 12 months
      while pergolide did not. Intracortical facilitation was always within the normal
      range. Motor thresholds were unchanged in both groups of patients over 12 months.
      Clinically, levodopa and pergolide improved motor Unified Parkinson's disease
      rating scale (UPDRS) scores at 6 months but only levodopa maintained benefit at
      12 months as compared to baseline. CONCLUSIONS: Levodopa and pergolide
      differentially affected cortical inhibitory circuits at 12 months. The
      progressive deterioration of restored intracortical inhibition with pergolide may
      be due to the development of tolerance and down-regulation of dopamine receptors.

PMID- 10880794
TI  - SFEMG in ocular myasthenia gravis diagnosis.
AB  - BACKGROUND AND OBJECTIVE: In typical cases, the patient's history and clinical
      examination make it possible to diagnose ocular myasthenia gravis (OMG). But, in
      many cases a clear clinical picture is not present and OMG diagnosis is very
      difficult because gold diagnostic standard tests are not available. The
      diagnostic tests for OMG are usually unable to display a good sensitivity and
      specificity simultaneously. In this paper, we studied 86 cases submitted for
      suspected OMG. METHODS: The patients were studied clinically and with various
      other tests used in OMG diagnosis (SFEMG, repetitive nerve stimulation, Ab anti
      AChR titration, tensilon test). RESULTS AND CONCLUSION: SFEMG showed the highest
      sensitivity (100%) while Ab anti AChR showed the highest specificity (100%). To
      our knowledge this is the largest population of suspected OMG studied using most
      of the diagnostic parameters, reported in the literature.

PMID- 10880795
TI  - Limitations on the clinical utility of the ulnar dorsal cutaneous sensory nerve
      action potential.
AB  - OBJECTIVE: To validate the clinical use of the ulnar dorsal cutaneous (UDCN)
      sensory nerve action potential (SNAP) in the topographical analysis of ulnar
      mononeuropathies and in the process of choosing a sensory nerve for biopsy.
      METHODS: We surveyed the UDCN SNAP electrophysiological characteristics in both
      hands of 97 normal volunteers aged 10-84 years. The nerve was recorded from the
      4th intermetacarpal space with subcutaneous needle electrodes and percutaneous
      stimulation was carried out at the wrist. RESULTS: In agreement with other
      studies, the mean conduction velocity was 58. 6+/-6.7 m/s, but the mean and the
      lower normal value of the amplitude (32 and 14.7 microV) were significantly
      higher than previous known data. An important finding was that in 21% of our
      population study, the UDCN SNAP was absent on at least one side, or a significant
      degree of asymmetry between the left and right sides was present. CONCLUSION: The
      UDCN SNAP is technically easy to obtain, but the high frequency of asymmetric or
      absent potentials detected in this study implies that caution should be taken in
      using this SNAP in clinical practice.

PMID- 10880796
TI  - Concentric needle EMG versus macro EMG I. Relation in healthy subjects.
AB  - OBJECTIVES: The relation between motor unit action potentials (MUAPs) recorded
      via a macro needle electrode (MA-MUAP, MA-EMG) and MUAPs recorded via a
      concentric needle electrode (CN-MUAP, CN-EMG) is under debate. In particular it
      is not known to what degree CN-MUAP variables reflect the electrical properties
      of a motor unit. METHODS: CN-EMGs and MA-EMGs of the right brachial biceps muscle
      were recorded from 40 healthy subjects (23 women and 17 men) aged 17-83 years and
      CN-MUAP and MA-MUAP variables were cross-correlated. RESULTS: CN-MUAP duration
      was positively and significantly correlated with CN-MUAP area (r=0.52), rate of
      polyphasia (r=0.45), MA-MUAP amplitude (r=0.47) and MA-MUAP area (r=0.45). CN
      MUAP amplitude was positively and significantly correlated with the rate of
      polyphasia (r=0.39) and the fibre density (r=0.45). CONCLUSIONS: CN-MUAP duration
      appropriately reflects the motor unit's electrical activity and may substitute MA
      MUAP area and amplitude.

PMID- 10880797
TI  - CNV and temporal uncertainty with 'ageing' and 'non-ageing' S1-S2 intervals.
AB  - OBJECTIVES: Uncertainty about the timing of a known external event is an everyday
      phenomenon but has been rarely investigated with electrophysiological methods. We
      studied how the amplitude of the contingent negative variation (CNV) is affected
      by temporal variation of S2 presentation. Competing hypotheses about the
      development of CNV during the foreperiod until S2 presentation were that CNV
      either would follow a monotonic trend, be it increasing or decreasing, or
      alternatively that the time-course of CNV would be affected by the probability
      with which S2 was presented at each time-point in a given task. METHODS: The
      interval between cueing stimulus and imperative stimulus was randomly chosen from
      3 different values between 1.3 and 2.6 s, using 3 different probability
      distributions in separate blocks: an 'ageing', a 'non-ageing' and a 'Gaussian'
      distribution. RESULTS: As previously shown, reaction times were determined by the
      probability of the imperative stimulus at the given length of the foreperiod. The
      same was found for CNV amplitude: the effects of temporal uncertainty on CNV
      mainly depended on the particular distribution of temporal probabilities used in
      a block. The relevant parameter was the a posteriori probability of event
      occurrence, very similar to the effects of this parameter on response times. In
      fact, the major part of the effect of a posteriori probability on CNV was common
      variation of CNV and response times. CONCLUSIONS: Thus, under temporal
      uncertainty the amplitude of CNV reflects the subjective expectancies for the
      occurrence of a given event, with this variation being related to variations in
      response times.

PMID- 10880798
TI  - Somatosensory evoked magnetic fields: relation to pre-stimulus mu rhythm.
AB  - OBJECTIVES: Brain responses to auditory and visual stimuli have been previously
      shown to depend on the level of spontaneous brain activity in the 8-13 Hz range.
      Our aim was to determine whether somatosensory evoked responses are influenced by
      ongoing rhythmic activity in the 8-13 Hz frequency range originating in the
      sensorimotor cortex (mu rhythm). METHODS: We used a whole-head 122 channel
      magnetoencephalography (MEG) system to record somatosensory evoked fields (SEFs)
      in response to median nerve stimulation in 11 subjects. Spontaneous oscillations
      in the 8-13 Hz band over the contralateral sensorimotor cortex were evaluated in
      3 different pre-stimulus time intervals using wavelet analysis. RESULTS: The N20m
      SEF deflection did not depend on pre-stimulus activity, while the amplitude of
      the P35m deflection, and to a lesser extent that of the P60m deflection, showed a
      small positive correlation with the amplitude of the pre-stimulus mu rhythm.
      Although the amplitude of the mu rhythm varied by a factor of 2.3-5, the maximum
      variations in P35m and P60m amplitude were only 21 and 12%, respectively. The
      latencies of the peaks were not affected by the strength of the pre-stimulus mu
      rhythm. CONCLUSIONS: It appears that the first excitatory cortical response
      (N20m) is independent of the oscillatory state (8-13 Hz frequency range) of the
      sensorimotor cortex. Later parts of the response (P35m and P60m) are also
      relatively stable compared with the large variations in mu rhythm.

PMID- 10880799
TI  - Vitamin A status in relation to electroretinographic and electrooculographic
      findings in HIV infection.
AB  - OBJECTIVES: To investigate the electrooculogram (EOG) and an expanded battery of
      electroretinograms (ERGs) in HIV-infected subjects without retinopathy at two
      different levels of immunosuppression. Consideration was given to the possible
      effects of serum levels of vitamin A. METHODS: Two groups of neurologically
      normal HIV-positive subjects with CD4+ cell counts of <200 (n=17) or >400 (n=19)
      were contrasted with 20 HIV-negative controls. Rod ERGs, oscillatory potentials
      and cone ERGs were obtained using ganzfeld stimulation. A sequence of dark- and
      light-adapted EOG recordings was analyzed to obtain light/dark ratios. The HIV
      positive subjects underwent a comprehensive ophthalmologic examination. RESULTS:
      Intergroup comparisons failed to reveal any significant intergroup differences.
      Abnormal ERG findings, those exceeding the 98% confidence limits, occurred in 11%
      (4/36) of the HIV-positive subjects. One of these subjects was hyporetinemic and
      another had a subnormal retinol level. No subjects had abnormal EOGs.
      CONCLUSIONS: HIV infection influenced retinal function in 11% of a group of
      neurologically normal subjects without clinical signs of retinopathy. The profile
      of electrophysiological findings suggested predominant functional deficits
      involving middle or inner retinal layers. Vitamin A deficiency and possible
      vascular changes could account for the observed ERG abnormalities.

PMID- 10880800
TI  - Shifting visual attention in space: an electrophysiological analysis using high
      spatial resolution mapping.
AB  - OBJECTIVES: Evidence from cortical electrophysiology and functional imaging
      converges on the view that visual spatial selective attention results in a
      facilitation of early sensory processing in visual cortical structures. Little is
      known, however, about the neural control processes that lead to this
      facilitation. The present study was aimed at further investigating these control
      processes and their neural correlates by analyzing high spatial resolution maps
      of brain activity that were evoked by attention-directing cues, but occurred
      prior to presentation of the target stimulus. METHODS: Subjects (n=14) were
      presented with central arrow cues that instructed them to attend covertly to
      either a left or right field location in order to compare two subsequent target
      stimuli simultaneously presented to the location. On half of the trials, targets
      were presented to the cued location, while in the other half, targets were
      presented to the opposite visual field location. Subjects had to respond via
      button press on 16% of the trials when target stimuli were identical. Event
      related potentials (ERPs) were recorded from 92 scalp electrodes which allowed a
      sufficiently finegrained analysis of the regional specificity of the ERP
      components. RESULTS: In response to the cues, an initial component over occipital
      parietal electrode sites was consistent with an early involvement of the
      posterior-parietal cortex, perhaps in the initial step of attentional orienting.
      A second component over the lateral-prefrontal cortex is consistent with the
      voluntary control and maintenance of attention, a function known to be subserved
      by frontal cortical structures. A late component narrowly focussed over occipital
      temporal electrode sites is most plausibly related to activation of parts of the
      ventral extrastriate cortex. CONCLUSIONS: The data support the current view that
      voluntarily orienting visual attention in space leads to top-down modulations in
      cortical excitability of ventral extrastriate regions initiated by posterior
      parietal and mediated by lateral-prefrontal cortical structures.

PMID- 10880801
TI  - The time course of high-frequency bands (15-45 Hz) in all-night spectral analysis
      of sleep EEG.
AB  - OBJECTIVE: The EEG spectral content of all-night sleep recordings obtained in 7
      healthy young subjects, aged 18-20 years, including frequencies up to 45 Hz, was
      studied in order to detect eventual changes in the high-frequency range similar
      to those reported by magnetic field recording during REM sleep at 40 Hz. METHODS:
      For this purpose, power spectra were calculated with a fast Fourier transform and
      the power of the bands ranging 0.75-4.50 Hz (Delta), 4.75-7.75 (Theta), 8.00
      12.25 (Alpha), 12.50-15.00 (Sigma), 15.25-24.75 (Beta), 25.00-34.75 (Gamma1), and
      35.00-44.75 (Gamma 2) was calculated for-the whole period of analysis (7 h). Also
      two additional time series: the ratio between Beta and Gamma2, and between Gamma1
      and Gamma2 were calculated (Beta and Gamma ratios). RESULTS: Beta and Gamma1
      showed small changes with a tendency to increase during REM sleep; Gamma2, on the
      contrary, showed small changes with a tendency to decrease during REM sleep. Beta
      and Gamma ratio peaks were clearly correlated with the occurrence of REM sleep.
      The small changes shown by Beta, Gamma1 and Gamma2 were not statistically
      significant; on the contrary, Beta ratio and Gamma ratio showed the most
      important statistical significance values being highest during REM sleep and
      lowest during slow-wave sleep. Finally, the calculation of the linear correlation
      coefficient and of the cross-correlation between the different bands showed a
      clear reciprocity between Delta and Beta and Gamma ratios. CONCLUSIONS: Our study
      shows a new method for the analysis of high frequencies (up to 45 Hz) in the
      scalp-recorded sleep EEG which allowed us to better define, as compared to
      previous studies on the same topic, the changes in power characteristically
      associated with REM sleep and correlated with the REM/non-REM ultradian rhythm,
      and to propose it as a tool for future studies.

PMID- 10880802
TI  - Effects of medial thalamotomy and pallido-thalamic tractotomy on sleep and waking
      EEG in pain and Parkinsonian patients.
AB  - OBJECTIVES: Investigation of sleep and sleep EEG before and after stereotactic
      neurosurgery. METHODS: All-night polysomnographic recordings were obtained in 3
      neurogenic pain patients and 3 parkinsonian patients. One subject of each group
      was recorded in addition 3 months after surgery. Stereotactic operations were
      performed in the medial thalamus and on the pallido-thalamic tract to relieve
      neurogenic pain and parkinsonian symptoms, respectively. RESULTS: Sleep
      efficiency was little affected by the surgical intervention in neurogenic pain
      patients and a dramatic reduction in REM sleep occurred, which had recovered in
      the subject recorded after 3 months. After the surgery parkinsonian patients
      showed an increase in total sleep time and in sleep efficiency, and a decrease in
      REM sleep latency. Sleep efficiency remained elevated in the 3 months follow-up.
      Medial thalamotomy abolished spindle frequency activity (SFA) in the power and
      coherence spectra in non-REM sleep stage 2 systematically. Pallido-thalamic
      tractotomy attenuated SFA only to varying degrees. After 3 months SFA had
      reemerged. The alpha peak of the waking EEG was shifted to lower frequencies
      after surgery in 5 of 6 patients and had reverted to the original frequency 3
      months later. CONCLUSIONS: Medial thalamotomy or pallido-thalamic tractotomy had
      acute and reversible effects on the EEG and long-term deleterious side effects of
      stereotactic surgery on sleep and sleep EEG are improbable. The results provide
      further evidence for the involvement of the human thalamus in the generation of
      sleep spindles.

PMID- 10880803
TI  - Effects of startle and laughter in cataplectic subjects: a neurophysiological
      study between attacks.
AB  - OBJECTIVES: Cataplexy, when unequivocally present together with excessive daytime
      sleepiness, is diagnostic for narcolepsy. Unfortunately, it is difficult to
      induce cataplexy during consultation. In this study we tried to assess presumed
      subclinical expressions of cataplexy using neurophysiological tests. METHODS: In
      this controlled explorative study, we studied 14 patients with a clear history of
      cataplexy and 12 matched controls using standard H-reflex, H/M ratios,
      audiospinal reflex, H-reflexes modulated by emotions and startle reflexes.
      RESULTS: H-reflexes were attenuated during laughter in patients as well as
      controls. Startle reflexes were increased in patients. Audiospinal reflexes were
      not influenced. CONCLUSIONS: The patterns found add relevant knowledge concerning
      pathophysiological mechanisms and involved brain areas in cataplexy, and may
      reflect subclinical expressions of cataplexy. The presumed specificity of the
      abolishment of H-reflexes during cataplectic attacks is questioned by our
      findings. The exaggerated startle reflex is in line with recent findings
      concerning involved brain areas in narcolepsy.

PMID- 10880804
TI  - Comparison of human ictal, interictal and normal non-linear component analyses.
AB  - OBJECTIVES: The non-linear properties of EEG and filtered rhythms obtained from
      healthy subjects and epileptic patients with complex partial seizures were
      analyzed to investigate whether EEG in different neurological states can be
      generated by the mechanism that integrates several non-linear dynamic systems.
      METHODS: The control EEG (from 26 healthy subjects), interictal EEG and ictal EEG
      (from 25 patients) were digitally filtered into delta (0.5-4 Hz), theta (4-8 Hz),
      alpha (8-13 Hz), beta (13-30 Hz) and gamma (30-40 Hz) components. The correlation
      dimension was calculated on each original signal and corresponding surrogate
      data. A new method was developed to accelerate the calculation of the correlation
      integral. Function P(m,r) was defined to visualize the meaning of the correlation
      dimension. The point critical to the estimation was determined by the P(m,r)
      function. RESULTS: The EEG in the control subjects and patients showed
      significantly lower correlation dimensions than the surrogate data. The delta,
      alpha, beta and gamma components from the control EEG exhibited similar
      complexity to the surrogate data, while only the alpha component from the
      interictal EEG presented the same dimension as the surrogate data. The
      correlation dimensions of the theta and alpha components remained the same when
      the neurological state changed from interictal EEG to ictal EEG. The complexity
      of the beta component was higher than the complexity of other components in both
      control subjects and patients. The correlation dimension of EEG was significantly
      correlated to the complexity of delta, theta, beta and gamma components.
      CONCLUSIONS: Our results suggest that EEG and filtered components in different
      neurological states demonstrate varied dynamic properties. The characteristics of
      neuronal networks can be differentiated by the dynamics of filtered components.
      Separating EEG into different dynamic systems may facilitate understanding of the
      mechanisms involved in the human EEG.

PMID- 10880805
TI  - The effect of a scalp reference signal on coherence measurements of intracranial
      electroencephalograms.
AB  - OBJECTIVE: To determine the effect of a scalp reference signal, such as that
      recorded from the mastoid or ear, on the coherence of referential intracranial
      electroencephalograms (EEGs). METHODS: The relationship between reference signal
      power and magnitude squared coherence (MSC) was determined from the theoretical
      expression of the coherence of referential recordings, obtained under the
      assumption that the reference signal is not correlated with the signals being
      studied. The effect of a contaminated reference signal on the coherence of
      intracranial EEGs was determined by measuring the MSC of both a recording of
      background EEGs with a simulated contaminated reference signal and a contaminated
      recording of a seizure. RESULTS: The MSC of referential intracranial EEGs is
      inflated due to the reference signal. This inflation is a function of the true
      MSC of the intracranial signals and the power of the reference and intracranial
      signals. The inflation is limited where reference signal power is smaller than
      the power of the intracranial signals; maximum inflation <0.1 when reference
      signal power=0.2xpower of intracranial EEGs and </=0.2 when reference signal
      power=0.5xpower of intracranial EEGs. A contaminated reference signal may have a
      considerable effect on MSC, however. The changes to the MSC spectrum that result
      from a contaminated reference primarily occur in an open-ended high-frequency
      band and may create an elevated plateau in this part of the MSC spectrum.
      CONCLUSIONS: The findings presented here suggest a scalp reference signal is
      suitable, with careful monitoring of the reference signal, for coherence analysis
      of intracranial EEGs. A reference signal will have a limited effect on the
      coherence of intracranial EEGs except when it is contaminated. In the event the
      reference signal is contaminated it should be possible to detect this from the
      stereotyped features of the coherence spectrum.

PMID- 10880806
TI  - Tangential derivative mapping of axial MEG applied to event-related
      desynchronization research.
AB  - OBJECTIVES: A problem with the topographic mapping of MEG data recorded with
      axial gradiometers is that field extrema are measured at sensors located at
      either side of a neuronal generator instead of at sensors directly above the
      source. This is problematic for the computation of event-related
      desynchronization (ERD) on MEG data, since ERD relies on a correspondence between
      the signal maximum and the location of the neuronal generator. METHODS: We
      present a new method based on computing spatial derivatives of the MEG data. The
      limitations of this method were investigated by means of forward simulations, and
      the method was applied to a 150-channel MEG dataset. RESULTS: The simulations
      showed that the method has some limitations. (1) Fewer channels reduce accuracy
      and amplitude. (2) It is less suitable for deep or very extended sources. (3)
      Multiple sources can only be distinguished if they are not too close to each
      other. Applying the method in the calculation of ERD on experimental data led to
      a considerable improvement of the ERD maps. CONCLUSIONS: The proposed method
      offers a significant advantage over raw MEG signals, both for the topographic
      mapping of MEG and for the analysis of rhythmic MEG activity by means of ERD.

PMID- 10880807
TI  - Quantification of intracranial contribution to rheoencephalography by a numerical
      model of the head.
AB  - OBJECTIVES: Partial contributions of intracranial and extracranial circulation to
      rheoencephalography (REG) remain uncertain. The main goal of this work is to
      determine theoretically the capability of REG techniques to reflect intracranial
      blood flow. METHODS: Head and current injection electrodes were computationally
      modeled to assess REG sensitivity to brain and scalp conductivity changes. Data
      obtained were related to tissue perfusions to calculate the partial contribution
      of cerebral blood perfusion to REG I, REG II and monopolar REG and to assess
      their amplitudes. RESULTS: When REG I and monopolar REG were used, the
      theoretical maximum of intracranial contribution was reached with large current
      injection electrodes, being 8% for REG I and 12% for monopolar REG. However, some
      specific REG II electrode arrangements showed a nil contribution of the
      extracranial circulation and a minimum influence of the electrode size.
      CONCLUSIONS: These results may explain the disagreement on REG origin and suggest
      a theoretically optimum electrode arrangement.

PMID- 10880808
TI  - Use of the collision technique to improve the accuracy of motor unit number
      estimation.
AB  - OBJECTIVE: To evaluate the risk of stimulating the same motor axon at different
      points along the median nerve when using the multiple point stimulation (MPS)
      technique and how this affects the accuracy of the motor unit number estimate
      (MUNE). METHODS: Using the MPS technique, MUNE in the median innervated intrinsic
      hand muscles was done on two normal subjects, a patient with carpal tunnel
      syndrome and one with prior poliomyelitis. The collision technique was then used
      to confirm whether two motor unit action potentials (MUAPs) with similar
      configurations and sizes were generated by the same motor unit. A new MUNE was
      recalculated after the repeated inclusion of the same motor unit had been
      excluded. RESULTS: While the risk of stimulating the same motor axon at widely
      separate locations of the median nerve was negligible in normal subjects, this
      risk was much higher in patients with a depleted motor neuron pool. This resulted
      in marked distortion of the calculated size of the average single MUAP and,
      consequently, inaccuracy of the MUNE. CONCLUSIONS: The inadvertent inclusion of
      the same motor units, if not recognized, can markedly affect the accuracy of the
      MUNE. The collision technique can be useful in minimizing this risk.

PMID- 10880809
TI  - Transcranial magnetic stimulation in Behcet's disease: a cross-sectional and
      longitudinal study with 44 patients comparing clinical, neuroradiological,
      somatosensory and brain-stem auditory evoked potential findings.
AB  - OBJECTIVES: To compare neurological involvement in Behcet's disease as documented
      by transcranial magnetic stimulation (TMS) with clinical, neuroradiological,
      somatosensory (SEP) and auditory evoked potential (BAEP) findings. METHODS: Forty
      four patients were studied over an 8 year period. Nine patients had follow-up
      studies done. TMS central motor conduction (CMC) studies to upper and lower limb
      muscles, brain magnetic resonance imaging (MRI), SEP, and BAEP testing were
      conducted. RESULTS: Thirty-nine patients had CMC slowing, decreased amplitude or
      absent motor evoked potentials (MEP); 5 of these patients were neurologically
      normal. Concordance of TMS results, clinical deficits, and MRI findings occurred
      in 36 of the 39 patients. SEP and BAEP testing proved non-complementary to MEP.
      Generally, follow-up studies revealed faster CMC and higher MEP amplitude.
      However, in two patients the CMC time to one target muscle became prolonged with
      diminished MEP amplitude over a period of 1.5-3 years. CONCLUSIONS: TMS can be
      useful in detecting and quantifying motor tract dysfunction in Behcet's disease
      and provides functional information complementary to imaging studies. TMS is more
      sensitive than either SEP or BAEP. Our longitudinal studies suggest that TMS
      studies may be valuable in monitoring disease activity or therapeutic response.

PMID- 10880810
TI  - Preservation of the brainstem auditory evoked potential in non-convulsive status
      epilepticus.
AB  - Brainstem auditory evoked potentials (BAEPs) were recorded from a patient
      simultaneously experiencing non-convulsive generalized status epilepticus (NGSE).
      Waves I, III and V were normal but all subsequent waves were absent. This finding
      indicates that structures within the brainstem adjacent to the generators for the
      BAEP are likely not affected by NGSE and also illustrates the resilient nature of
      the BAEP. This is the first report of the recording of an evoked potential during
      a naturally occurring generalized seizure.

PMID- 10880811
TI  - Volatiles as an indicator of fungal activity and differentiation between species,
      and the potential use of electronic nose technology for early detection of grain
      spoilage.
AB  - There is significant interest in methods for the early detection of quality
      changes in cereal grains. The development of electronic nose technology in recent
      years has stimulated interest in the use of characteristic volatiles and odours
      as a rapid, early indication of deterioration in grain quality. This review
      details the current status of this area of research. The range of volatiles
      produced by spoilage fungi in vitro and on grain are described, and the key
      volatile groups indicative of spoilage are identified. The relationship between
      current grain quality descriptors and the general classes of off-odours as
      defined in the literature, e.g. sour, musty, are not very accurate and the
      possible correlation between these for wheat, maize and other cereals, and
      volatiles are detailed. Examples of differentiation of spoilage moulds and
      between grain types using an electronic nose instrument are described. The
      potential for rapid and remote grain classification and future prospects for the
      use of such technology as a major descriptor of quality are discussed.

PMID- 10880812
TI  - Field monitoring Sitophilus zeamais and Sitophilus oryzae (Coleoptera:
      Curculionidae) using refuge and flight traps baited with synthetic pheromone and
      cracked wheat.
AB  - Flight traps with open vertical baffles and refuge traps in the form of
      rectangular cardboard boxes were used to catch Sitophilus zeamais and S. oryzae
      in Kenya. Traps baited with the aggregation pheromone (Sitophilure), and for the
      first time traps baited with pheromone and food bait (cracked wheat), were field
      tested. Both traps types were effective in capturing Sitophilus spp and gave
      higher weevil catch when baited with pheromone and cracked wheat combined than
      with pheromone or cracked wheat alone. The combination of pheromone and cracked
      wheat had an additive effect on trap catch and not a synergistic effect as
      reported in earlier laboratory trials. Different pheromone loadings of 0.5, 1 and
      2 mg were tested. The catch of S. zeamais in flight traps rose significantly with
      increasing dosage. For refuge traps, the same effect was observed although the
      difference between 1 mg and 2 mg was not statistically significant. The trend was
      for increasing S. oryzae catch with dosage, although total catches were very much
      lower than those for S. zeamais, and differences did not prove statistically
      significant. Traps placed on the floor near infested maize cribs captured
      significantly more Sitophilus spp than those actually placed in the cribs. Adult
      Sitophilus captured were sexed and in both flight and refuge traps the sex ratio
      was biased in favour of females even though the sex ratio of weevils from
      infested maize cobs, which were the source of the captured weevils, was
      approximately even.

PMID- 10880813
TI  - Effect of various essential oils on Callosobruchus maculatus (F.) (Coleoptera:
      Bruchidae).
AB  - Essential oils were extracted from four West African plant species [Tagetes
      minuta (Family Compositae), Hyptis suaveolens (Family Labiatae), white basil
      Ocimum canum (Family Labiatae), and sweet basil O. basilicum (Family Labiatae)]
      by steam distillation. The oil of the pepper Piper guineense (Family Piperaceae),
      was extracted from the fruits by hydro distillation and ethanol extraction. Mixed
      essential oil and total ethanol extract was used. Kaolin powder (clay) was mixed
      (aromatized) with these different oils. Cowpea weevils were reared on chickpeas
      and newly emerged males and females were deposited on uninfested seeds.
      Bioassays, i.e. fumigation with pure essential oils and aromatized kaolin
      powders, were carried out on adults and eggs. Twenty four hours after fumigation,
      99 and 0% adult mortality were observed, respectively, as the result of
      treatments with Ocimum basilicum and the control. The application of powders
      aromatized with the same oils to weevil pairs resulted in a complete lack of
      oviposition, whereas 31, 56 and 76 eggs were laid in the controls after 24, 48
      and 72 h, respectively. Application of aromatized powders did not have a
      significant effect on egg hatching (50 out of 110 with O. canum, 100 out of 115
      with O. basilicum and 100 out of 130 in the control sample) but did have a
      significant impact on adult emergence: 0% for the two treatments compared with
      100% in the controls. Our results suggest that plants of the genus Ocimum can be
      used as an alternative to synthetic insecticides.

PMID- 10880814
TI  - The influence of storage practices on aflatoxin contamination in maize in four
      agroecological zones of Benin, west Africa.
AB  - Aflatoxin level in 300 farmers' stores in four agro-ecological zones in Benin, a
      west African coastal country, were determined over a period of 2 years. At
      sampling a questionnaire was used to evaluate maize storage practices. Farmers
      were asked what storage structure they used, their storage form, storage period,
      pest problems in storage and what was done against them. Beninese farmers often
      changed their storage structures during the storage period, transfering the maize
      from a drying or temporary store to a more durable one. Most of the farmers
      complained about insects damaging stored maize. Often, storage or cotton
      insecticides were utilized against these pests. Regression analysis identified
      those factors that were associated with increased or reduced aflatoxin.Maize
      samples in the southern Guinea and Sudan savannas were associated with higher
      aflatoxin levels and the forest/savanna mosaic was related to lower toxin levels.
      Factors associated with higher aflatoxin were: storage for 3-5 months, insect
      damage and use of Khaya senegalensis-bark or other local plants as storage
      protectants. Depending on the agroecological zone, storage structures that had a
      higher risk of aflatoxin development were the "Ago", the "Secco", the "Zingo" or
      storing under or on top of the roof of the house. Lower aflatoxin levels were
      related to the use of storage or cotton insecticides, mechanical means or smoke
      to protect against pests or cleaning of stores before loading them with the new
      harvest. Fewer aflatoxins were found when maize was stored in the "Ago" made from
      bamboo or when bags were used as secondary storage containers.

PMID- 10880815
TI  - Cross-resistance of a chlorpyrifos-methyl resistant strain of Oryzaephilus
      surinamensis (Coleoptera: Cucujidae) to fumigant toxicity of essential oil
      extracted from Eucalyptus globulus and its major monoterpene, 1,8-cineole.
AB  - The fumigant toxicities of eucalyptus essential oil and 1,8-cineole, the major
      component of eucalyptus oil, were tested against a chlorpyrifos-methyl resistant
      strain and a reference strain of the sawtoothed grain beetle, Oryzaephilus
      surinamensis (L.). The resistant strain showed 1.9- and 2.2-fold higher tolerance
      against essential oil and 1,8-cineole fumigation toxicity, respectively, relative
      to the susceptible strain. The increased tolerance for the essential oil may be
      the result of cross-resistance. The resistance mechanisms in the resistant strain
      are discussed in relation to elevated detoxifying enzymes such as cytochrome P450
      and esterases.

PMID- 10880816
TI  - Central mechanisms in the control of penile erection: current theory and
      research.

PMID- 10880817
TI  - Neural pathways and central sites involved in penile erection: neuroanatomy and
      clinical implications.
AB  - Penile erection occurs in response to tactile, visual, and imaginative stimuli in
      humans. In animals olfactory and auditory cues are particularly important. The
      participation of multiple sites with the brain and spinal cord, and coordination
      of somatic and autonomic pathways make sexual behavior in general, and erection
      in particular, vulnerable to neurologic injury and disease. Sites within the
      brain and spinal cord act in concert to process, coordinate, then distribute the
      neural inputs necessary for sexual behavior including erection. Activation of
      neurons in some of these regions either pharmacologically or by electrical
      stimulation has been associated with penile tumescence. This review will provide
      a geographic framework for understanding the neuroanatomical basis of penile
      erection based primarily on animal data. Following discussion of the anatomical
      substrates, a clinical correlation is then provided to confirm and reinforce
      these experimental observations.

PMID- 10880818
TI  - Central neural regulation of penile erection.
AB  - Penile erection is caused by a change of the activity of efferent autonomic
      pathways to the erectile tissues and of somatic pathways to the perineal striated
      muscles. The spinal cord contains the cell bodies of autonomic and somatic
      motoneurons that innervate the peripheral targets. The sympathetic outflow is
      mainly antierectile, the sacral parasympathetic outflow is proerectile, and the
      pudendal outflow, through contraction of the perineal striated muscles, enhances
      an erection already present. The shift from flaccidity to erection suggests
      relations among these neuronal populations in response to a variety of
      informations. Spinal neurons controlling erection are activated by information
      from peripheral and supraspinal origin. Both peripheral and supraspinal
      information is capable of eliciting erection, or modulating or inhibiting an
      erection already present. One can hypothesize a spinal network consisting of
      primary afferents from the genitals, spinal interneurons and sympathetic,
      parasympathetic and somatic nuclei. This system is capable of integrating
      information from the periphery and eliciting reflexive erections. The same spinal
      network, eventually including different populations of spinal interneurons, would
      be the recipient of supraspinal information. Premotor neurons that project
      directly onto spinal sympathetic, parasympathetic or somatic motoneurons, are
      present in the medulla, pons and diencephalon. Several of these premotor neurons
      may in turn be activated by sensory information from the genitals. Aminergic and
      peptidergic descending pathways in the vicinity of spinal neurons, exert complex
      effects on the spinal network that control penile erection. This is caused by the
      potential interaction of a great variety of receptors and receptor subtypes
      present in the spinal cord. Brainstem and hypothalamic nuclei (among the latter,
      the paraventricular nucleus and the medial preoptic area) may not necessarily
      reach spinal neurons directly. However they are prone to regulate penile erection
      in more integrated and coordinated responses of the body, such as those occurring
      during sexual behavior. Finally, the central and spinal role of regulatory
      peptides (oxytocin, melanocortins, endorphins) has only recently been elucidated.

PMID- 10880819
TI  - Some proposals regarding the organization of the central nervous system control
      of penile erection.
AB  - Recent research on the central nervous control of penile erection is discussed. A
      framework for this control is based upon principles put forward by Frank Beach
      regarding the neuroendocrine regulation of male copulatory behavior. The current
      discussion is focused primarily on a subset, penile erection. The spinal cord
      contains all the necessary components for the production of penile erection. This
      requires a multisegmental coordination among penile vasodilator and
      vasoconstrictor autonomic neurons, pudendal motoneurons responsible for penile
      rigidity and autonomic neurons which control extra-penile blood flow. Genital
      sensory stimulation can activate this spinal network. The spinal cord is also
      under excitatory and inhibitory control from supraspinal sites. Penile erection
      can be driven by supraspinal input alone and supraspinal control can inhibit the
      erectile effects of genital stimulation.An important aspect of the CNS control of
      penile erection is that there are extensive interconnections between most of the
      brain sites identified to date. Most of the pathways are characterized by
      reciprocal connections. A large number of the CNS sites also receive genital
      sensory information. Thus, descending control may itself be modulated by
      ascending sensory pathways which relay information from the genitalia. This
      raises the possibility that penile erection may involve a positive feedback
      system. Receptors for gonadal hormones have been identified throughout the
      neuraxis. However, strong evidence for the control of male sexual function by
      gonadal hormones has been identified only for forebrain sites. The functional
      role of brainstem and spinal gonadal hormone receptors has not yet been
      clarified.

PMID- 10880820
TI  - Contextual approaches to the physiology and classification of erectile function,
      erectile dysfunction, and sexual arousal.
AB  - This paper offers a reexamination of some long-held beliefs relating to the
      physiology of erectile function and dysfunction, including the idea that there is
      a singular physiology of erection. Rather, there appear to be plural neural,
      neurochemical, and endocrine mechanisms whose participation in erectile function
      depends on the behavioral context in which erection occurs. The best examples of
      this context-dependent physiology come from research on rats. For example, the
      medial amygdala is essential for noncontact erection in response to inaccessible
      estrous females, but not for erection during copulation. Also, androgen is
      necessary for touch-based and noncontact erection, but not for erection during
      copulation. Even the specific dopamine receptors important to erection may
      differ, depending on the context. If there is not a singular physiology of
      erection, then it follows that the physiology of erectile dysfunction may also
      vary from context to context. Thus, some disorders of the central nervous system
      may not be manifested in sleep-related erection, and therefore may be
      misinterpreted as "psychogenic" erectile dysfunction. This term belies the axiom
      that all psychological processes have a somatic basis; therefore, there can be no
      psychogenic dysfunction that does not involve organic processes which may respond
      to pharmacotherapy. A revised classification of erectile dysfunction based on
      this premise is offered. Finally, closer attention to erectile context may also
      illuminate male "sexual arousal" and its relation to "sexual motivation". The
      former term has so many meanings in current usage as to impede research,
      especially into the physiology of sexual arousal, which depends on comparisons
      between animals and humans. It is proposed that attention be given to two
      variables: whether or not erection occurs and whether or not the context is
      sexual. The occurrence of penile erection within a sexual context is viewed as
      the only case in which sexual arousal may be inferred unambiguously.

PMID- 10880821
TI  - Central neuropharmacological agents and mechanisms in erectile dysfunction: the
      role of dopamine.
AB  - Central nervous system processes are fundamental to sexual function. Considerable
      progress has been made in our understanding of the neuroanatomical and
      neuropharmacological bases for erection. Based largely on rat models, there is
      adequate understanding presently of the general anatomical areas of the brain
      that relate to sexual function, including the medial amygdala, medial preoptic
      area, paraventricular nucleus, the periaqueductal gray, ventral tegmentum and
      others. There is also a burgeoning body of evidence implicating nitric oxide,
      dopamine, serotonin and oxytocin as critical central neurotransmitters involved
      in various aspects of sexual function. The role of dopamine, in particular,
      appears fundamental in the mediation of erectile responses in both animals and
      man. Additionally, clinical research with apomorphine, a D1/D2 agonist, has shown
      significant promise in improving erections in men with a wide range of erectile
      difficulties. Finally, a new classification matrix has been proposed for existing
      treatments for erectile dysfunction based upon the putative site and mechanism of
      action. Implications for the further development of neuropharmacological agents
      in this area are discussed.

PMID- 10880822
TI  - The dual control model of male sexual response: a theoretical approach to
      centrally mediated erectile dysfunction.
AB  - A theoretical model of dual control of male sexual response is considered, based
      on the balancing of central excitation and inhibition, with individuals varying
      in their propensity for both sexual excitation and inhibition of sexual response.
      A questionnaire method for measuring propensities for sexual excitation and
      inhibition has been developed (SIS/SES questionnaire), resulting in one
      excitation factor (SES) and two inhibition factors (SIS1 and SIS2). Evidence for
      the existence of both inhibitory and excitatory tone is discussed. The first
      inhibition factor (SIS1) may be related to level of inhibitory tone and is
      associated with fear of performance failure. The second inhibition factor (SIS2)
      may be related to external threats (e.g. from within the sexual relationship).
      The implications for the treatment of centrally mediated erectile dysfunction are
      discussed, with predictions that high SIS2 individuals will respond to
      psychological treatment, whereas high SIS1 individuals will respond better to
      pharmacological methods of treatment.

PMID- 10880823
TI  - Adeno-associated virus vectors: activity and applications in the CNS.
AB  - Transgenic strategies are useful for functional studies and they may also lead to
      novel therapies. Controlling transgene expression in defined cell populations
      over time is increasingly important for both functional and gene therapy
      experiments. The adeno-associated virus (AAV) vector may provide sufficient
      spatio-temporal control of gene expression for these purposes. This paper reviews
      in vivo somatic gene transfer methodology using AAV. Advantageous features of
      this system include neuronal gene expression that is: (1) efficient; (2) long
      lived; and (3) non-toxic. Thus, AAV-mediated gene transfer is a good method for
      functional genomic research. From characterizing vector activity in the brain
      using different combinations of promoters and transgenes in the mid to late
      1990s, researchers continue to discover novel uses of AAV for both basic and
      clinical neuroscience.

PMID- 10880824
TI  - Polyimide cuff electrodes for peripheral nerve stimulation.
AB  - This paper describes a new tripolar spiral cuff electrode, composed of a thin (10
      microm) and flexible polyimide insulating carrier and three circumneural platinum
      electrodes, suitable for stimulation of peripheral nerves. The cuffs were
      implanted around the sciatic nerve of two groups of ten rats each, one in which
      the polyimide ribbon was attached to a plastic connector to characterize the in
      vivo stimulating properties of the electrode, and one without a connector for
      testing possible mechanical nerve damage by means of functional and histological
      methods. The polyimide cuff electrodes induced only a very mild foreign body
      reaction and did not change the nerve shape over a 2-6 month implantation period.
      There were no changes in the motor and sensory nerve conduction tests,
      nociceptive responses and walking track pattern over follow-up, and no
      morphological evidence of axonal loss or demyelination, except in one case with
      partial demyelination of some large fibers after 6 months. By delivering single
      electrical pulses through the cuff electrodes graded recruitment curves of alpha
      motor nerve fibers were obtained. Recruitment of all motor units was achieved
      with a mean charge density lower than 4 microC/cm(2) for a pulse width of 50
      micros at the time of implantation as well as 45 days thereafter. These data
      indicate that the polyimide cuff electrode is a stable stimulating device, with
      physical properties and dimensions that avoid nerve compression or activity
      induced axonal damage.

PMID- 10880825
TI  - A novel technique for micro-dissection of neuronal processes.
AB  - A simple system for cutting dendrites of single neurons without damaging the
      viability of the cell is described. The system utilizes a rapidly vibrating (100
      Hz) micropipette (<1 microm tip diameter), which is dragged under direct visual
      control across the dendrite of a selected neuron. We used this system in a thin
      slice preparation to dissect the apical dendrites of rat hippocampal CA1
      pyramidal cells. We then used the patch-clamp technique in the whole-cell
      configuration to record from the isolated somata of these cells and to inject a
      dye into them. Both a functional and an anatomical disconnection of the dendrites
      from their somata were verified.

PMID- 10880826
TI  - A parallel algorithm for simulation of large neural networks.
AB  - The simulation of biologically realistic neural networks requires the numerical
      solution of very large systems of differential equations. Variables within the
      system can be changing at rates that vary by orders of magnitude, not only at
      different times of the solution, but at the same time in different parts of the
      network. Therefore, an efficient implementation must be able to vary the solution
      step size, and do so independently in different subsystems. A single processor
      algorithm is presented in which each neuron can be solved with its own step size
      by using a priority queue to integrate them in the correct order. But this leaves
      the problem of how communication and synchronisation between neurons should be
      managed when executing in parallel. The proposed solution uses an algorithm based
      on waveform relaxation, which allows groups of neurons on different processors to
      be solved independently and hence in parallel, for substantial parts of the
      computation. Realistic test problems were run on a distributed memory parallel
      computer and results show that speedups of 10 using 16 processors are achievable,
      and indicate that further speedups may be possible.

PMID- 10880827
TI  - Pulsed plasma deposition of allylamine on polysiloxane: a stable surface for
      neuronal cell adhesion.
AB  - Allylamine was pulse-plasma polymerized onto a hydrophobic polysiloxane substrate
      to create cell adhesion surfaces for cell culture that would not require
      pretreatment with polylysine, could be sterilized via autoclaving, and could be
      re-used for several culture cycles. We investigated two different plasma
      deposition protocols at 200 W RF power: (1) a duty cycle of 3 ms on and 5 ms off;
      and (2) a cycle of 3 ms on and 45 ms off. Control surfaces were unmodified
      polysiloxane, activated polysiloxane via flaming, and flamed polysiloxane further
      modified with poly-D-lysine (PDL). The different surfaces were characterized with
      XPS analysis, water contact angle, and cell adhesion and growth using dissociated
      murine embryonic spinal tissue. We found that both the amine content of the 3/45
      duty cycle surface and the wettability was higher than that of the 3/5 surface.
      Also, spinal cord cells were better dispersed 24 h after seeding on the 3/45
      surface, suggesting a difference in early adhesion dynamics. However, the
      networks on the two types of modified surfaces revealed no obvious morphological
      differences after 2 weeks in vitro. The stability of allylamine-decorated
      surfaces after autoclaving was high with only minor changes in wettability and
      nitrogen content. Cell growth on such surfaces after autoclaving was comparable
      to that found on flamed polysiloxane, freshly modified with PDL. Allylamine
      surfaces were still usable as cell growth substrates after three autoclaving
      cycles, 4 weeks under warm culture medium, and simple cleaning procedures,
      indicating the achievement of a long-lasting modification that did not require
      the repeated use of PDL before each seeding.

PMID- 10880828
TI  - Long-term maintenance of mature hippocampal slices in vitro.
AB  - Cultures of primary neurons or thin brain slices are typically prepared from
      immature animals. We introduce a method to prepare hippocampal slice cultures
      from mature rats aged 20-30 days. Mature slice cultures retain hippocampal
      cytoarchitecture and synaptic connections up to 3 months in vitro. Spontaneous
      epileptiform activity is rarely observed suggesting long-term retention of normal
      neuronal excitability and of excitatory and inhibitory synaptic networks.
      Picrotoxin, a GABAergic Cl(-) channel antagonist, induced characteristic
      interictal-like bursts that originated in the CA3 region, but not in the CA1
      region. These data suggest that mature slice cultures displayed long-term
      retention of GABAergic inhibitory synapses that effectively suppressed
      synchronized burst activity via recurrent excitatory synapses of CA3 pyramidal
      cells. Mature slice cultures lack the reactive synaptogenesis, spontaneous
      epileptiform activity, and short life span that limit the use of slice cultures
      isolated from immature rats. Mature slice cultures are anticipated to be a useful
      addition for the in vitro study of normal and pathological hippocampal function.

PMID- 10880829
TI  - Computer-assisted visualizations of neural networks: expanding the field of view
      using seamless confocal montaging.
AB  - Microscopic analysis of anatomic relationships within the neural networks of
      adult and developing tissues often requires sampling large spatial regions of
      neuronal architecture. To accomplish this, there are two common imaging
      approaches: (1) image the entire area at once with low spatial resolution; or (2)
      image small sections at higher magnification/resolution and then join the
      sections back together by mosaic reconstruction (photomontaging). Low
      magnification imaging is relatively rapid to perform, resulting in a
      visualization that encompasses a large field of view with an extended depth of
      field. However, for fluorescence microscopy, low magnification visualizations are
      often plagued by poor spatial resolution. High magnification imaging possesses
      superior spatial resolution, but it produces an image with limited depth of
      field. When creating a larger field of view, the final image is also fragmented
      at the boundaries where multiple images are stitched together. Using confocal
      microscopy as well as features of common image processing programs, we outline a
      new method to transform individual, spatially contiguous z-series into a montage
      with a seamless field of view and an extended depth of field. In addition, we
      show that the manual alignment of images our method requires does not introduce
      significant errors into the final image. We illustrate our method for visualizing
      neural networks using tissues from the adult gastropod mollusc, Tritonia
      diomedea, and the developing zebrafish, Danio rerio.

PMID- 10880830
TI  - New methods of dye application for staining motor neurons in an insect.
AB  - Motor neurons innervating tiny muscles in the antennal system of the cockroach,
      Periplaneta americana, were stained by two new approaches to backfilling motor
      axons and somata. Both methods are easier, and produce less leakage of dye, than
      conventional methods that rely on application of dye to the distal cut end of a
      motor nerve or immersion of a whole muscle in dye. One approach used here was to
      pressure-inject nickel (or cobalt) chloride directly into a muscle from a
      micropipette. The other was to place filter paper soaked in nickel chloride on
      the muscle surface. The first approach enabled staining of motor neurons most
      reliably and with preservation of stain to the specific muscle of interest. The
      second approach had different advantages: it was easier to perform, resulted in
      more intense staining and frequently more complete staining of dendritic
      structure than the first approach. Taken together, these two approaches should
      prove useful for tracing motor circuits in a number of model systems.

PMID- 10880831
TI  - The use of biotinylated compounds or reagents is much more complicated than
      originally thought.

PMID- 10880832
TI  - Corrigendum to 'Methods to evaluate functional nerve recovery in adult rats:
      walking track analysis, video analysis and the withdrawal reflex'.

PMID- 10880833
TI  - Experimental erythrocytic malaria infection induces elevated serum amyloid P
      production in mice.
AB  - Experimental blood-stage malaria infection of NIH mice was observed to induce an
      acute phase response (APR). Infection of mice with either P. chabaudi, P. vinckei
      (both non-lethal) or P. berghei (lethal infection) resulted in elevated serum
      amyloid P (SAP) production, the major acute phase protein in mice. Peak
      production occurred at the peak of the parasitaemia (approximately day 10 post
      infection). SAP isolated from the serum of P. chabaudi infected mice was shown to
      inhibit the growth of intra-erythrocytic malaria parasites in vitro. Furthermore,
      isolated SAP suppressed the proliferative response of splenocytes taken from a
      naive mouse to concanavalin A. To assess if SAP had a protective role in vivo
      during experimental blood-stage infection, IL-6 deficient mice, which have a
      significantly reduced APR, were infected with P. chabaudi. A significant
      extension to the primary parasitaemia was observed in IL-6 deficient mice
      compared to infected wild type mice. These observations demonstrate that blood
      stage malaria infection induces a systemic APR and that this may contribute to
      the immune response to infection in an anti-parasitic or immunomodulatory manner.

PMID- 10880834
TI  - Direct stimulation of macrophages by IL-12 and IL-18--a bridge too far?
AB  - A novel pathway of autocrine macrophage activation based on a positive feedback
      loop involving interleukin (IL)-12, IL-18 and IFN-gamma has recently been
      suggested. However, the macrophage isolation technique employed to describe the
      above phenomenon does not allow obtaining a pure population of macrophages
      casting some doubt to its existence. In the present study, we show that even
      minor contamination with lymphoid cells of a pure population of macrophage-like
      cells (Raw 264.7) results in a marked production of nitric oxide after
      stimulation with both IL-12 and IL-18. Neither macrophage-like cells nor lymphoid
      cells were capable of secreting high amounts of nitric oxide after stimulation
      with IL-12 and/or IL-18. Based on these observations we hypothesize that proposed
      autocrine feedback loop of macrophage activation is rather paracrine in nature
      and involves direct stimulation of residual lymphoid cells to secrete IFN-gamma
      that is then capable of activating macrophages.

PMID- 10880835
TI  - Establishment and usefulness of an anti-human CD57 IgG1 monoclonal antibody.
AB  - In the present study we established a new monoclonal antibody, JNK-1, which
      recognizes all cells recognized by CD57/HNK-1 mAb. JNK-1 and CD57 mAbs inhibited
      the binding of each other, suggesting that the molecules they recognize are
      either identical or sufficiently close to cause steric hindrance in the binding
      assay. JNK-1 mAb detected the 110-kDa protein, which is identical to the protein
      recognized by CD57/HNK-1 mAb in Western immunoblot analysis combined with
      immunoprecipitation. Therefore, JNK-1 mAb appears to recognize homogeneous
      molecules identified by the currently available CD57 mAb. Notably, JNK-1 mAb is
      composed of mouse IgG1 heavy chains, and thus can be used easily in
      immunoprecipitation, which cannot easily be performed with the available CD57 mAb
      because it is an IgM isotype. Thus, JNK-1, which is an IgG isotype, may present a
      useful tool to elucidate the CD57 protein.

PMID- 10880836
TI  - Nicotine switches the form of H(2)O(2)-induced cell death from apoptosis to
      necrosis in U937 cells.
AB  - Cigarette smoking is a major risk factor for lung diseases and oral diseases. The
      present study examined the effect of nicotine on H(2)O(2)-induced apoptosis in
      U937 cells. In the presence of 1 microg/ml nicotine, cell viability was not
      affected, but the cells were unable to undergo H(2)O(2)-induced apoptosis and
      instead died as a result of necrosis. Nicotine reduced the intracellular level of
      ATP, which is an important determinant of the form of cell death. These results
      suggest that nicotine can alter the cell death pathway by reducing the level of
      intracellular ATP, and that this effect may contribute to cigarette smoke-induced
      tissue destruction.

PMID- 10880837
TI  - Atomic force microscopy to study the effects of ITIM-bearing FcgammaRIIB on the
      activation of RBL-2H3 cells.
AB  - We have studied here the effects of ITIM-bearing FcgammaRIIB2 on the
      FcvarepsilonRI-dependent activation of rat basophilic leukemia (RBL-2H3) cells by
      atomic force microscopy (AFM). AFM images showed that ruffling and degranulation
      of RBL-2H3 cells were significantly reduced but the cell spreading was not by the
      co-clustering of FcgammaRIIB2 and FcvarepsilonRI. From the results it was shown
      that the co-clustering of ITIM-bearing negative co-receptors in a single RBL cell
      hardly induce the degranulation though the [Ca(2+)](i) increased transiently in
      the cell. This suggested that secretory responses and the membrane ruffling which
      were induced by the crosslinkng of FcgammaRII should be negatively controlled by
      the co-clustering of FcgammaRII.

PMID- 10880838
TI  - Analysis of 'natural' and vaccine-induced haemophilus influenzae type B capsular
      polysaccharide serum antibodies for 3H1, a V3-23-associated idiotope.
AB  - The variable (V-) region repertoire of antibodies (Abs) to Haemophilus influenzae
      capsular polysaccharide (Hib PS) has been extensively studied in individuals
      vaccinated against the microbe, but to a lesser extent in subjects who generated
      such Abs in response to a 'natural' encounter with this microbe or its antigenic
      mimics. To gain an insight into the repertoire of Hib PS-reactive Abs in
      vaccinated and non-vaccinated individuals, we used a monoclonal Ab, 3H1, which
      detects an idiotypic marker associated with an Ab V-region gene, V3-23. We show
      here that Hib PS-reactive Abs with detectable 3H1 idiotope can be quantified by
      an indirect inimunoezymatic assay in serum samples of non-vaccinated healthy
      adults as well as of recently vaccinated healthy infants. The percentage of Abs
      that was simultaneously Hib PS-reactive and 3H1-positive ranged widely (from 0 to
      68%) among individual serum samples from both groups of subjects. No dramatic
      differences in the expression of 3H1 idiotope on Hib PS-reactive Abs were found
      between vaccinated and non-vaccinated individuals. Our results are consistent
      with the hypothesis that the utilization of V-region genes in Hib PS-reactive Abs
      that individuals generate after a 'natural' encounter with Hib PS or its mimics
      is similar to that in these Abs elicited by Hib PS conjugate vaccines.

PMID- 10880839
TI  - Multiple HLA-class I-specific inhibitory NK receptor expression and IL-4/IL-5
      production by CD8+ T-cell clones in HIV-1 infection.
AB  - Several mechanisms may contribute to the decline in HIV-1 specific CD8+ cytotoxic
      T-lymphocyte (CTL) activity that is observed in infected patients, including loss
      of CD4+ cell help, antigenic shift, impaired clonogenicity and functional
      impairment due to expression of inhibitory NK receptors (iNKRs). In addition to a
      decrease in HIV-1-specific cytolytic activity, an increased proportion of CD8+ T
      cells producing IL-4 and IL-5 has been recently observed in advanced HIV-1
      infection. Remarkably, an impaired HIV-1-specific CTL activity was primarily
      detected among the TC0/Tc2 CD8+ CTLs. A series of CD3+CD8+ T-cell clones
      expressing inhibitory NK receptors (iNKRs) isolated from HIV-1 infected patients
      was analyzed in order to determine their cytokine production pattern and to
      assess the extent of iNKR expression at the single cell level. Our data indicate
      that iNKR+CD3+CD8+ clones isolated from infected patients frequently express
      multiple iNKR and may produce IL-4 and IL-5 to a relevant extent.

PMID- 10880840
TI  - Association of decreased phosphorylation of ERK-2 with costimulation of rat T
      cell activation by MEK-1 inhibitors and TGF-beta1.
AB  - Transforming growth factor-beta (TGF-beta) is usually known as an
      immunosuppressive cytokine, but we and others have shown stimulatory effects of
      TGF-beta on activation of Th2 T-lymphocytes. In the present investigation we have
      studied the effect of TGF-beta1 on phosphorylation of ERK, a MAP-kinase
      downstream of the Ras pathway. ERK is phosphorylated by MEK-1 and PD098059 and
      U0126 are specific inhibitors for this kinase. We demonstrate in the present
      study that these inhibitors abrogate the inhibitory effect of adh-splc (adherent
      spleen cells) on activation of primary rat T-cells and induce a strong
      costimulatory effect almost as strong as we have previously shown with TGF-beta1.
      When TGF-beta1 is acting stimulatory on T-cell activation, it decreases
      phosphorylation of ERK-2 and thereby its activation. To investigate whether TGF
      beta1 and MEK-1 inhibitors influence the same pathways, we compared their effects
      on cytokine profiles associated with SEA-induced rat T cell activation. TGF-beta1
      induced IL-10 production, slightly decreased TNF-alpha production and decreased
      IFN-gamma production. The PD098059 inhibitor decreased both IFN-gamma and TNF
      alpha production and together with TGF-beta1, it totally blocked IFN-gamma, TNF
      alpha and IL-10 production. Thus TGF-beta1 and PD098059 showed overlapping but
      not identical effects on the cytokine pattern.

PMID- 10880841
TI  - Epitope mapping on N-terminal region of taenia solium paramyosin.
AB  - Epitope mapping of the amino-terminal 20aa sequence from Taenia solium paramyosin
      (TPmy), an immunodominant protein involved in the complex host-parasite
      relationship in human and porcine cysticercosis is reported. A 12-mer random
      peptide phage display library was screened with antibodies raised against a
      synthetic peptide corresponding to the amino-terminal 20aa sequence of TPmy, its
      highly immunodominant region. In total, 57 clones isolated in two panning
      conditions were analyzed, of which a single group of 14 sequences found in 25
      clones shared a consensus motif showing structural similarity with the antigen
      Arg10-Thr16 region.

PMID- 10880842
TI  - Nicotine effects on proliferation and the bombesin-like peptide autocrine system
      in human small cell lung carcinoma SHP77 cells in culture.
AB  - OBJECTIVES: To determine whether nicotine affects the proliferation and
      expression of the bombesin-like peptide autocrine system in human small cell lung
      carcinoma (SCLC) SHP77 cells compared with nonmalignant human bronchial
      epithelial BEAS 2B cells as non-neuroendocrine controls. METHODS: Human lung
      cells were cultured in defined serum-free medium with various concentrations of
      nicotine added for various times. Proliferation was measured by cell counts and
      colorimetric assay, bombesin-like peptide receptor expression was assayed by
      specific binding assays and quantitative competitive PCR, and bombesin-like
      peptides determined by ELISA. RESULTS: Nicotine significantly stimulated the
      growth of human SCLC SHP77 and NCI-H865 cells, but not BEAS 2B cells. Bombesin
      like peptide receptor specific binding and mRNA expression were not affected by
      nicotine exposure in SHP77 cells or BEAS 2B cells. An increase in SHP77 cellular
      bombesin-like peptide content was observed. CONCLUSIONS: Human SCLC SHP77 cells
      express the components of the bombesin-like peptide autocrine system. Increased
      proliferation in the presence of nicotine may be due in part to increased levels
      of bombesin-like peptides in SHP77 cultured in nicotine. Nicotine effects on
      nonmalignant pulmonary neuroendocrine cells may provide additional insight into
      how nicotine itself may promote lung carcinogenesis.

PMID- 10880843
TI  - The angiopoietins, tie2 and vascular endothelial growth factor are differentially
      expressed in the transformation of normal lung to non-small cell lung carcinomas.
AB  - The successful establishment of angiogenesis depends on a complex process of
      endothelial proliferation and organization. The angiopoietins (Ang-1 and Ang-2)
      and Tie2 ligand-receptor system is essential for the regulation of vascular
      maturation and stability during embryonic development. Together with the vascular
      endothelial growth factor (VEGF)-mediated pathway, they have been implicated in
      the control of normal physiological angiogenesis. We investigated their potential
      role and interaction in the development of lung cancers by comparing the
      expression pattern and inter-relationship of Ang-1 and 2, Tie2 and VEGF levels in
      28 pairs of primary non-small cell lung cancers (NSCLC) and normal lung. Using
      semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in
      situ hybridization (ISH), we showed that in NSCLC, there was significantly up
      regulated VEGF expression by the tumour cells and an increased intensity of Ang-2
      expression in the tumour vessels. The number of Ang-2-expressing vessels also
      correlated with the grades of tumour cell expression of VEGF. On the other hand,
      normal lung expressed constitutively high and correlated levels of Ang-1 and
      Tie2, which were significantly reduced in the carcinomas. The findings suggested
      a role of the Ang-1/Tie2 pathway in the maintenance of the complex vasculature in
      normal lung, while collaborative activities between the Ang-2 and VEGF pathways
      might be important in promoting tumour angiogenesis in NSCLC.

PMID- 10880844
TI  - Immunohistochemical detection of mutant p53 protein in small-cell lung cancer:
      relationship to treatment outcome.
AB  - We investigated the expression of mutant p53 proteins in small-cell lung cancer
      (SCLC) immunohistochemically, by identification of stabilized mutant p53 proteins
      with a much longer half-life than the wild-type protein. Of 103 tumor specimens
      obtained by transbronchial tumor biopsy for histologic diagnosis, 52 (50%) showed
      positive staining for p53 protein with a p53 monoclonal antibody, DO-1. Positive
      staining for p53 protein was not correlated with age, sex, performance status,
      lifetime cigarette consumption, serum concentration of neuron-specific enolase
      and extent of disease. Complete response rates in patients with a mutant p53
      protein-positive tumor were significantly lower than those in p53-negative
      patients (25% versus 59%; P=0.0005, by chi-square test). Similarly, survival
      periods in patients with a mutant p53 protein-positive tumor were significantly
      shorter than those in mutant p53-protein-negative patients (10.8 months versus
      20.6 months; P=0.0001, by generalized Wilcoxon test). Multivariate analysis using
      Cox's proportional hazards model revealed that the presence of mutant p53 protein
      is an independent factor associated with differences in overall survival (hazards
      ratio=2.72; 95% confidence interval, 1.71-4.34; P=0.0001). These observations
      suggest that the expression of mutant p53 proteins in SCLC may be an important
      factor predicting poor prognosis.

PMID- 10880845
TI  - Biological variables in non-small cell lung cancer: comparison between
      immunocytochemical determination on fine needle aspirates from surgical specimens
      and immunohistochemical determination on tissue sections.
AB  - A number of biological and predictive markers of non-small cell lung cancer
      (NSCLC) have been sought, but these have so far been mainly evaluated on
      surgically resected specimens. Given that fine needle aspiration biopsy (FNAB) is
      being increasingly used in the diagnosis of NSCLC, its application could be
      extended to the immunocytochemical detection of biological parameters at the time
      of diagnosis before surgery. In order to assess the reliability of estimating
      biological markers on fine needle aspirates (FNAs) from NSCLC, the aim of this
      study was to compare Ki67 growth fraction, p53 and bcl-2 protein expression as
      revealed by the immuncytochemical assessment of FNAs obtained from surgical
      samples with the immunohistochemical results obtained from the corresponding
      histological sections. FNAs were performed on surgical specimens obtained from 29
      NSCLC patients. Ki67, p53 and bcl-2 were cytologically and histologically
      evaluable in respectively 25, 27 and 19 cases. Concordance between FNAs and
      corresponding paraffin sections was 84% for Ki67, 93% for p53 and 95% for bcl-2.
      All of the specimens whose biological parameters were studied by
      immunocytohistochemistry also underwent flow cytometric DNA analysis of FNAs
      taken from fresh surgical specimens. Of the 29 cases, 22 were aneuploid and seven
      diploid. The S-phase fraction (SPF) was evaluable in 62% of cases. Comparison of
      SPF results on FNAs with Ki67 values evaluated on the corresponding histologic
      and cytologic specimens, revealed a significant correlation only with histology.
      Good reproducibility was also found in relation to the immunocytochemical results
      obtained on FNAs from different areas of the same tumour, showing that tumour
      heterogeneity does not affect the method. The concordance between the
      immunocytochemical and immunohistochemical results suggests that FNAB may be a
      reliable procedure for the biological characterization of NSCLC. Given its
      limited invasiveness, FNAB could be used in vivo for the preoperative assessment
      of biological parameters in patients with operable or metastatic NSCLC.

PMID- 10880846
TI  - Transsternal approach to closure of bronchopleural fistulas after pneumonectomy.
      A fifteen cases report.
AB  - A treatment method for main bronchus fistula after pneumonectomy via median
      sternotomy was described by P. Abruzzini in 1961. This operation is performed in
      an area not involved with infection. Fifteen patients underwent the procedure in
      our surgical department; one of them died of myocardial infarction while all the
      others survived for different periods of time, closely associated with the
      original disease; seven were long-term survivors. The transmediastinal approach
      seems an effective means of managing such a difficult complication.

PMID- 10880847
TI  - A preoperative alternating chemotherapy and radiotherapy program for patients
      with stage IIIA (N2) non-small cell lung cancer.
AB  - The objective of the present study was to evaluate the feasibility and toxicity
      of a preoperative alternating chemotherapy and radiotherapy program followed by
      surgery in stage IIIA non-small cell lung cancer (NSCLC). The tumor response,
      resection rate, tumor/lymph node downstaging, and survival were also evaluated.
      The positive predictive value (PPV) in the diagnosis of mediastinal lymph node
      metastasis was 81% using conventional magnetic resonance imaging (MRI) with short
      inversion-time inversion recovery (STIR) technique (STIR-MRI) on our criteria.
      Eligible patients had clinical N2 lesions (stage IIIA) and a World Health
      Organization (WHO) performance status of 0-2. The treatment program consisted of
      two courses of preoperative cisplatin, vindesine, and ifosfamide; alternating
      with radiotherapy, including two courses of 20 Gy radiation. Surgery was
      performed within 4 weeks after the treatment. Twenty-two patients with stage IIIA
      (N2) NSCLC (20 men and two women, age 35-71 years) were enrolled into the study.
      Hematologic and other toxicities were within an acceptable range. Surgery was not
      indicated for two patients because of distant metastasis; one patient with renal
      dysfunction and one with pancytopenia during this treatment underwent surgery
      subsequently. The clinical response rate was 50% (partial response in 11/22).
      Definitive surgery was indicated for 18 patients resulting in 17 patients with
      complete resection and one exploratory thoracotomy. A pathologic complete
      response of the primary tumor occurred in 41% of the patients (seven of 17;
      without residual tumor), whereas 58% (ten of 17) were pathologic N0. The median
      survival was 33 months with an actuarial 4-year survival rate of 33% in 17
      patients with complete resection and 30 months with 28% 4-year survival rate in
      all entered patients. A randomized phase-III study using this approach for stage
      IIIA (clinical N-2 disease) is warranted.

PMID- 10880848
TI  - The potential role of amifostine in the treatment of non small cell lung cancer.
AB  - Amifostine protects healthy tissues but not tumor cells from the damage induced
      by cytotoxic treatments, particularly ionizing radiations, alkylating and
      platinating agents. The clinical effectiveness of amifostine has been
      demonstrated by randomized trials in ovarian and head-and-neck cancer patients
      treated with chemotherapy with or without radiation therapy. The available
      pharmacoeconomic data confirm a favorable cost/utility ratio. The majority of non
      small cell lung cancer (NSCLC) patients receive radio and/or chemotherapy. A role
      for amifostine in these patients has been hypothesized, and some experiences
      performed. The aim of this paper is to outline the present role of amifostine in
      the treatment of NSCLC.

PMID- 10880849
TI  - A phase II trial testing gemcitabine as second-line chemotherapy for non small
      cell lung cancer. The European Lung Cancer Working Party.
      101473.1044@compuserve.com.
AB  - The purpose of the present trial was to determine the activity of gemcitabine as
      a second-line chemotherapy for non small cell lung cancer (NSCLC). To be
      eligible, patients had to have pathologically proven NSCLC that has failed to
      respond to a first-line chemotherapy with a cisplatin-containing regimen, a
      Karnofsky performance status greater than 50 and adequate renal, haematological
      and hepatic functions. After registration, patients were treated by gemcitabine
      given i.v. at a dose of 1 g/m(2) on days 1, 8, 15 every 4 weeks. Response was
      assessed after two courses of therapy. Eighty-two patients have been registered,
      five are ineligible and 65 are assessable for response. Four partial responses
      were observed (6%). No change was documented in 18 cases (28%). Tolerance was
      good. A few grade III leucopenia and grade III-IV thrombopenia were observed. We
      conclude that gemcitabine has a modest activity as second-line chemotherapy for
      NSCLC. It has the advantage to be well tolerated and may thus be one drug to be
      proposed to the patients who have disease progression after a first-line
      chemotherapy and who ask for further treatment.

PMID- 10880850
TI  - Lung cancer and tobacco control. What do we have to do... more?

PMID- 10880851
TI  - Reciprocal communication systems between astrocytes and neurones.
AB  - Over the past decade, a growing body of evidence has emerged on the existence in
      the brain of a close bidirectional communication system between neurones and
      astrocytes. This article reviews recent advances in understanding the rules
      governing these interactions and describes putative, novel functions attributable
      to astrocytes in neuronal transmission. Astrocytes can respond to the
      neurotransmitter released from active synaptic terminals, with cytosolic Ca(2+)
      oscillations whose frequency is under the dynamic control of neuronal activity.
      In response to these neuronal signals, astrocytes can signal back to neurones by
      releasing various neurone active compounds, such as the excitatory
      neurotransmitter glutamate. Interestingly, there is accumulating evidence that
      glutamate is released via a Ca(2+)-dependent mechanism which may share common
      properties with neurotransmitter exocytosis in neurones. This bidirectional
      communication system between neurones and astrocytes may lead to profound changes
      in neuronal excitability and synaptic transmission. While there clearly is an
      enormous amount of experimental and theoretical work yet to figure out, a
      coherent view is now emerging which incorporates the astrocyte, with the
      presynaptic terminal and the postsynaptic target neurone, as a possible third
      functional element of the synapse.

PMID- 10880852
TI  - Auditory sensori-neural alterations induced by salicylate.
AB  - Early after the development of aspirin, almost 150 years ago, its auditory
      toxicity has been associated with high doses employed in the treatment of chronic
      inflammatory diseases. Tinnitus, loss of absolute acoustic sensitivity and
      alterations of perceived sounds are the three auditory alterations described by
      human subjects after ingestion of large doses of salicylate. They develop over
      the initials days of treatment but may then level off, fluctuate or decrease, and
      are reversible within a few days of cessation of treatment. They may also occur
      within hours of ingestion of an extremely large dose. Individual subjects vary
      notably as to their susceptibility to salicylate-induced auditory toxicity.
      Tinnitus may be the first subjective symptom, and is often described as a
      continuous high pitch sound of mild loudness. The hearing loss is slight to
      moderate, bilaterally symmetrical and affects all frequencies with often a
      predominance at the high frequencies. Alterations of perceived sounds include
      broadening of frequency filtering, alterations in temporal detection,
      deterioration of speech understanding and hypersensitivity to noise. Behavioral
      conditioning of animals provides evidence for mild and reversible hearing loss
      and tinnitus, similar to those observed in humans. Anatomical examinations
      revealed significant alterations only at outer hair cell lateral membrane.
      Electrophysiological investigations showed no change in endocochlear resting
      potential, and small changes in the compound sensory potentials, cochlear
      microphonic and summating potential, at low acoustic levels. Measures of cochlear
      mechanical responses to sounds indicated a clear loss of absolute sensitivity and
      an associated broadening of frequency filtering, both of a magnitude similar to
      audiometric alterations in humans, but at extremely high salicylate levels.
      Otoacoustic emissions demonstrated changes in the mechano-sensory functioning of
      the cochlea in the form of decrease of spontaneous emissions and reduced
      nonlinearities. In vitro measures of isolated outer hair cells showed reduction
      of their fast motile responses which are thought to be at the origin of cochlear
      absolute sensitivity and associated fine filtering. Acoustically evoked neural
      responses from the eighth nerve to the auditory cortex showed reversible and mild
      losses of absolute sensitivity and associated broadening of frequency filtering.
      There is no evidence of a direct alteration of cochlear efferent innervation.
      Evidence was obtained for decreases in cochlear blood supply under control of
      autonomous innervation. Spontaneous neural activity of the auditory nerve
      revealed increases in firings and/or in underlying temporal synchronies. Similar
      effects were found at the inferior colliculus, mostly at the external nucleus,
      and at the cortex, mostly at the anterior and less at the secondary auditory
      cortex but not at the primary auditory cortex. These changes in spontaneous
      activity might underlie tinnitus as they affect mostly neural elements coding
      high frequencies, can occur without a loss of sensitivity, are dose dependent,
      develop progressively, and are reversible. Biochemical cochlear alterations are
      poorly known. Modifications of oxydative phosphorylation does not seem to occur,
      involvement of inhibition of prostaglandin synthesis appears controversial but
      could underlie changes in blood supply. Other biochemical alterations certainly
      also occur at outer hair cells and at afferent nerve fibers but remain unknown.

PMID- 10880854
TI  - Metabolism and functions of glutathione in brain.
AB  - The tripeptide glutathione is the thiol compound present in the highest
      concentration in cells of all organs. Glutathione has many physiological
      functions including its involvement in the defense against reactive oxygen
      species. The cells of the human brain consume about 20% of the oxygen utilized by
      the body but constitute only 2% of the body weight. Consequently, reactive oxygen
      species which are continuously generated during oxidative metabolism will be
      generated in high rates within the brain. Therefore, the detoxification of
      reactive oxygen species is an essential task within the brain and the involvement
      of the antioxidant glutathione in such processes is very important. The main
      focus of this review article will be recent results on glutathione metabolism of
      different brain cell types in culture. The glutathione content of brain cells
      depends strongly on the availability of precursors for glutathione. Different
      types of brain cells prefer different extracellular glutathione precursors.
      Glutathione is involved in the disposal of peroxides by brain cells and in the
      protection against reactive oxygen species. In coculture astroglial cells protect
      other neural cell types against the toxicity of various compounds. One mechanism
      for this interaction is the supply by astroglial cells of glutathione precursors
      to neighboring cells. Recent results confirm the prominent role of astrocytes in
      glutathione metabolism and the defense against reactive oxygen species in brain.
      These results also suggest an involvement of a compromised astroglial glutathione
      system in the oxidative stress reported for neurological disorders.

PMID- 10880853
TI  - The role of oxidative stress in the toxicity induced by amyloid beta-peptide in
      Alzheimer's disease.
AB  - One of the theories involved in the etiology of Alzheimer's disease (AD) is the
      oxidative stress hypothesis. The amyloid beta-peptide (A beta), a hallmark in the
      pathogenesis of AD and the main component of senile plaques, generates free
      radicals in a metal-catalyzed reaction inducing neuronal cell death by a reactive
      oxygen species mediated process which damage neuronal membrane lipids, proteins
      and nucleic acids. Therefore, the interest in the protective role of different
      antioxidants in AD such as vitamin E, melatonin and estrogens is growing up. In
      this review we summarize data that support the involvement of oxidative stress as
      an active factor in A beta-mediated neuropathology, by triggering or facilitating
      neurodegeneration, through a wide range of molecular events that disturb neuronal
      cell homeostasis.

PMID- 10880855
TI  - Diagrammatic approach to calculation of the fluctuation correlation matrix in a
      metabolic system.
AB  - We present here a simple diagrammatic approach for the time evolution of the
      fluctuations in metabolite concentrations around the steady state. A fluctuation
      correlation matrix is introduced to characterise the response in the
      concentrations of metabolites to a singular initial fluctuation in one of the
      metabolites. We show how the temporal evolution of the correlation matrix can be
      represented in the form of a series with individual terms corresponding to
      pathways on a metabolic graph. The basic properties of such graphs are studied
      and it is shown how each term in the series can be evaluated. A Monte-Carlo
      procedure is outlined to calculate the fluctuation correlation matrix. We discuss
      various properties of the graphical representation and discuss links to
      information theory that arise from it.

PMID- 10880856
TI  - The kinetic effect of product instability in a Michaelis-Menten mechanism with
      competitive inhibition.
AB  - In most kinetic studies it is assumed that both the reactant and the products are
      stable. However, under certain conditions spontaneous decomposition or
      deterioration caused by one of the participating species occurs. Studies, in
      which a species (the free enzyme, the enzyme-substrate complex, an inhibitor or
      the product of the reaction) is unstable, have appeared in the literature.
      However, to our knowledge, the enzymatic systems, in which a competitive
      inhibition and a decomposition or transformation of the products take place
      simultaneously, have not been studied so far. In this paper, we present a kinetic
      analysis of an enzyme reaction that follows a Michaelis-Menten mechanism, in
      which the free enzyme suffers a competitive inhibition simultaneously with the
      decomposition of the immediate product. In this study, we have linearised the
      differential equations that describe the kinetics of the process. Under the
      assumption of limiting concentration of enzyme, we have obtained and tested the
      explicit equation describing the time dependence of the product concentration
      using numerical calculus. With this equation and the experimental progress curve
      of the product, we constructed an easy procedure for the evaluation of the
      principal kinetic parameters of the process.

PMID- 10880857
TI  - A non-statistical approach to protein mutational variability.
AB  - The non-statistical, non-Markovian model of protein mutational variability is
      described. There are presented the essential features of the algorithm of genetic
      semihomology and some examples of its application. The results of genetic
      semihomology approach are compared with the results obtained by using statistical
      algorithms and matrices which are assumed in widely used programs such as
      ClustalW, FASTA, MultAlin and BLAST. The aim of the new algorithm elaboration is
      to improve the accuracy of the results of protein sequence comparison, avoid the
      wrong assumptions and misinterpretation of the results, and increase the amount
      of information available from such study.

PMID- 10880858
TI  - Classical and quantum dynamics on p-adic trees of ideas.
AB  - We propose mathematical models of information processes of unconscious and
      conscious thinking (based on p-adic number representation of mental spaces).
      Unconscious thinking is described by classical cognitive mechanics (which
      generalizes Newton's mechanics). Conscious thinking is described by quantum
      cognitive mechanics (which generalizes the pilot wave model of quantum
      mechanics). The information state and motivation of a conscious cognitive system
      evolve under the action of classical information forces and a new quantum
      information force, namely, conscious force. Our model might provide mathematical
      foundations for some cognitive and psychological phenomena: collective conscious
      behavior, connection between physiological and mental processes in a biological
      organism, Freud's psychoanalysis, hypnotism, homeopathy. It may be used as the
      basis of a model of conscious evolution of life.

PMID- 10880859
TI  - Enzymes as molecular automata: a stochastic model of self-oscillatory glycolytic
      cycles in cellular metabolism.
AB  - A stochastic model based on the molecular automata approach was developed to
      simulate the cyclic dynamics of glycolysis-gluconeogenesis in cell energy
      metabolism. The stochastic algorithm, based on Gillespie's method, simulates the
      master equation associated with any network of enzymatically controlled
      reactions. This model of the glycolytic-gluconeogenetic cycle was developed by
      assembling the stochastic kinetic reactions controlled by two enzymes:
      phosphofructokinase (PFKase) and fructose-1, 6-biphosphatase (FBPase). In order
      to obtain the hysteresis behaviour predicted by classical Sel'kov analysis, a
      minimum complexity is required in the allosteric regulations. This implies that
      the FBPase cannot have a single binding site for its transition to the inactive
      state (a minimum of two or three binding sites is necessary). Given the
      multimeric structure of this enzyme, this kinetic hypothesis is tenable. Other
      possible applications of the stochastic automata approach for different cases of
      channels, receptors and enzymatic control are suggested.

PMID- 10880860
TI  - Strict ESS for n-species systems.
AB  - A system of n asexual populations is considered where both intra- and
      interspecific frequency-dependent game conflicts with lack of information take
      place. The concept of a strict n-species ESS is introduced which implies local
      asymptotic stability of the replicator dynamics of pure phenotypes. The dynamical
      concept of strict stability is also introduced which turns out to be equivalent
      to the strict n-species ESS concept. The above notions are also related to
      similar concepts considered in the literature for the same biological situation.

PMID- 10880862
TI  - Thermal avoidance and preference in Daphnia magna.

PMID- 10880861
TI  - The rearranged genetic code and its implications in evolution and biochemistry.
AB  - We rearrange the genetic code and present a table of codons. The chemical
      properties of the amino acids coded by codons, and the evolutionary trend of
      codons are well reflected in the order of this table, from which two rules can be
      drawn: (1) the polarity/non-polarity and hydrophilicity/hydrophobicity of amino
      acids coded for by codons alternate row by row in the table; (2) in general, the
      lower down in the table, the earlier the codons are in terms of evolution.

PMID- 10880863
TI  - A sexually dimorphic response in supercooling temperature, enhanced by
      starvation, in the lesser mealworm Alphitobius diaperinus (Coleoptera:
      Tenebrionidae).
AB  - The effect of starvation on supercooling temperature (SCP) distribution was
      investigated in adults and larvae of Alphitobius diaperinus (Coleoptera:
      Tenebrionidae).The mean values for SCPs of adults fed at 20 degrees C were 
      14.5+/-2.4 degrees C (31 males) and -10.3+/-1.3 degrees C (29 females). The
      distribution of the SCPs of these control adults was unimodal. No significant
      differences were observed in either mean wet weight or mean dry weight between
      males and females.The mean values for SCPs of adults starved for 1 month at 20
      degrees C were found to be bimodal due to sexual dimorphism. The mean SCPs for
      males was lower (-17+/-2.6 degrees C; 28) than that for females (-11.2+/-1.8
      degrees C; 26). No significant differences were observed in either mean dry
      weight or wet weight between males and females.The SCPs of both fed and starved
      larvae, kept for 1 month at 20 degrees C were -12.3+/-2.4 degrees C (fed) and 
      18.0+/-2.6 degrees C (starved).

PMID- 10880864
TI  - Muscle temperature in free-swimming giant Atlantic bluefin tuna (Thunnus thynnus
      L.).
AB  - Muscle temperature was measured by telemetry in giant Atlantic bluefin tuna
      whilst the tuna were free-swimming in large pounds. Muscle temperature tended to
      remain steady at about 24 degrees C; water temperature ranged from 9 to 17
      degrees C. Muscle temperature was much less variable than stomach temperature in
      these fish. Muscle temperature varied less than 3 degrees C whereas stomach
      temperature varied by as much as 14 degrees C.

PMID- 10880865
TI  - Thermal biology of the fossorial rodent Ctenomys fulvus from the Atacama desert,
      northern Chile.
AB  - The Andean tuco-tuco, Ctenomys fulvus (Rodentia: Ctenomyidae) inhabits one of the
      most arid regions of the world, the Salar de Atacama, Northeast of Antofagasta,
      Chile (23 degrees 17'06"S, 68 degrees 05'43"W; 2.240 m.a.s.l). We found that a
      stable microclimate in burrows, a low evaporative water loss (EWL), and a diet of
      roots (59% water content) are the main factors that permit the survival of this
      fossorial species in harsh desert conditions. Large circadian variation in T(a)
      was observed above ground. Daily DeltaT(a) (T(a) max - T(a) min) = 37.9+/-0.2
      degrees C in summer and in winter. In contrast, circadian variation of T(a)
      inside the burrows was only 5.8+/-0.5 degrees C in the same seasons. Relative
      humidity (RH) was 1.9-3.1% during the day, increasing to maximum values of 27% at
      night and early morning. Inside the burrows RH was higher and quite stable,
      ranging between 53.1 and 65%, independent of the time of day and season. EWL,
      measured between 10 and 25 degrees C, was low (1.26 mg/g h), and a moderate
      increase of 13-20% was observed at higher temperatures. The low EWL may prevent
      dehydration. However, because of the low heat loss capability, animals became
      hyperthermic (0.8-1.6 degrees C) in dry air at T(a)=30-35 degrees C. As T(a)
      during afternoon normally exceeded 35 degrees C, the microclimate of burrows
      provided the only way to avoid the lethal effects of hyperthermia.

PMID- 10880866
TI  - Reactions of central neurons to peripheral thermal stimuli in the snail Helix
      pomatia L.
AB  - In Helix pomatia L. recordings have been made of 91 single neurons from the
      cerebral ganglia during peripheral thermal stimulation of the lip region.
      Temperatures ranged between 12 and 32 degrees C. Different reactions to thermal
      stimulation could be observed: hyperpolarisation (n=43), depolarisation (n=9),
      increasing frequency of action potentials (n=10), decreasing frequency of action
      potentials (n=3). A number of cells did not show any changes in neuronal activity
      (n=26). The assumption that distinct cell clusters are responsible for the
      processing of thermal stimuli had to be rejected since cells responding to
      peripheral thermal stimulation were found in all parts of the ganglia.

PMID- 10880867
TI  - Role of beta adrenoceptors in metabolic and cardiovascular responses of cold
      exposed humans.
AB  - Effect of a nonspecific beta adrenergic blocker - propranolol (40 mg per os) on
      thermoregulatory responses of cold water immersed (12.5 degrees C) humans was
      studied. Propranolol attenuates resting and cold induced thermogenesis, rectal
      temperature, heart rate and systolic blood pressure, but increases production of
      adrenaline and cortisol. Propranolol has no effect on the threshold body
      temperature for induction of cold thermogenesis and on central thermosensitivity.
      The following conclusions are drawn from consideration of the data presented:
      During the early phase of cooling (20 min after the start of cooling) the
      thermogenesis mediated by beta adrenergic receptors may cover about 80% of the
      total metabolic increase induced by cold. After about 30 min of cooling the
      relative proportion of beta adrenergic thermogenesis starts to decline, reaching
      20% of the total cold thermogenesis at the end of cooling.It can be suggested
      from consideration of the data that, in man, the beta adrenergic receptors in the
      heart, blood vessels, adipocytes and muscles participate in mediating effect of
      cold on cardiovascular and thermoregulatory responses. Furthermore, these data
      imply that human adrenergic thermogenesis is produced outside of the brown
      adipose tissue. Thus, physiological mechanisms mediating adrenergic thermogenesis
      in humans appear to be different from those in small mammals.

PMID- 10880868
TI  - Variation in the expression of Hsp70, the major heat-shock protein, and
      thermotolerance in larval and adult selection lines of Drosophila melanogaster.
AB  - (1) Lines of Drosophila melanogaster were "laboratory naturally" or artificially
      selected under five thermal regimes. (2) Hsp70 expression per unit protein after
      heat hardening and heat-shock resistance with and without prior hardening were
      measured. (3) Differences between the selection regimes in the responses of these
      traits suggest that thermal resistance can be changed independently of inducible
      Hsp70 expression. (4) Adult males had higher survival than females but did not
      differ in inducible Hsp70 expression per unit protein after heat hardening. (5)
      Larvae expressed less Hsp70 per unit protein than adults after heat hardening.

PMID- 10880869
TI  - Relative tolerance of cirripede larval stages to acute thermal shock: A
      laboratory study.
AB  - (1) Meroplankters drawn into once-through cooling circuits of coastal power
      plants are subjected to transient thermal stress. The effect of such acute
      thermal shock on the development of barnacle larvae was studied in the
      laboratory.(2) The response of the barnacle larvae (naupliar and cyprid stages)
      to elevated temperature was dependent on exposure time and their stage of
      development.(3) Among the stages tested, N-6 larvae showed maximum tolerance.
      Exposure to 37 degrees C did not affect larval survival, but delayed development
      of N-2 larva to cypris by one day.(4) Exposure at 40 degrees C delayed, hastened
      or did not affect the development time of N-2 and N-4 larvae through cypris,
      depending on exposure time.(5) Ten mins exposure at 43 degrees C proved lethal to
      all larval stages with mortality ranging from 20 to 86%.(6) Development success
      of the surviving larvae, measured in terms of cypris yield, showed no significant
      difference from controls, at temperatures below 40 degrees C.(7) Settlement
      activity was significantly affected in only those cyprid larvae which were
      exposed to 43 degrees C for 10 min.(8) Results of the present study indicate that
      thermal stress experienced in the once-through cooling system does not have
      significant impact on survival and development of the barnacle larvae at
      temperatures of 37-40 degrees C.

PMID- 10880870
TI  - The effect of short-term fasting on shivering thermogenesis in Japanese quail
      chicks (Coturnix coturnix japonica): indications for a significant role of diet
      induced/growth related thermogenesis.
AB  - (1) The effect of short-term fasting on metabolism and shivering thermogenesis
      was studied in 9-day-old Japanese quail. (2) After 31 h of fasting, heat
      production decreased 39% and body temperature over 2 degrees C in the
      thermoneutral zone. The difference in heat production between control and fasting
      groups decreased with decreasing ambient temperature. (3) Despite the lower
      metabolic rate, the amplitudes of shivering EMGs were higher in fasted chicks,
      especially in pectoralis. This indicates that fasted quails used shivering to
      compensate the decrease in diet-induced/growth related thermogenesis. (4) In
      cold, conductance of control birds decreased simultaneously with increasing heat
      production while in fasted chicks, conductance decreased to its minimum before
      heat production was activated. (5) Japanese quail chicks adapt quickly to short
      term fasting by decreasing metabolism but they maintain their ability to
      thermoregulate in cold. Diet-induced/growth related thermogenesis has a
      significant role in thermoregulation since it reduces the need of shivering
      thermogenesis.

PMID- 10880871
TI  - Physiological blocking of the mechanisms of cold death: theoretical and
      experimental considerations.
AB  - The cold inhibited functions of skin thermoreceptors, of the thermoregulation
      centre, and the respiration centre during deep hypothermia can be restored
      without rewarming the body. The methods used were developed to test the
      hypothesis that during deep hypothermia calcium ion concentration [Ca(2+)](i) in
      the cytoplasm increases. This causes a perturbation of cell metabolism, the
      impairment of cell membrane function that cause the inhibition of cell
      functioning, resulting in cell death. Such an increase in [Ca(2+)](i) most likely
      would result from an energy deficit in a deeply cooled cell, which would
      compromise the processes that maintain the [Ca(2+)](i) at about 10(-7) M. These
      processes require large amounts of energy since they occur against a large
      concentration gradient. With the use of EDTA the extracellular concentration of
      Ca(2+) has been lowered by 15-27%, so reducing the concentration gradient for
      Ca(2+) between the cell and the medium and in consequence facilitated the process
      the extrusion of cell Ca(2+).During a period of cooling, sufficient to impair
      normal functioning, the experimental lowering of blood Ca(2+) allowed the
      restoration of normal function without the need to rewarm. In such cases the
      animals survived after cooling the body to temperatures at which they would
      normally have succumbed. The data presented support the stated hypothesis that
      the impairment of cellular function in mammals by low temperatures is the result
      of an uncorrected rise in [Ca(2+)](i).

PMID- 10880872
TI  - The heat shock response of adult Artemia franciscana.

PMID- 10880873
TI  - Comparative physiology of body fluid regulation in vertebrates with special
      reference to thirst regulation.
AB  - The origin of life took place in the ancient sea where the ionic concentration is
      thought to have been somewhat lower than that of the present day seas. This may
      partly explain why most vertebrate species have plasma ionic concentrations
      roughly one-third of seawater. Exceptions are primitive marine cyclostomes whose
      plasma is almost identical to seawater, and marine cartilaginous fishes that
      accumulate urea in plasma to increase osmolarity to a seawater level. The
      mechanisms for regulation of water and electrolyte balance should have evolved
      from these animals into those of more advanced ones in which plasma ions are
      regulated to one-third of seawater irrespective of the habitat. Although most
      extant terrestrial and aquatic animals maintain similar plasma osmolarity and
      ionic concentrations, the mechanisms of regulation differ greatly among different
      groups of animals according to their habitat. An outstanding difference is that
      while plasma Na(+) concentration is a primary factor of regulation in terrestrial
      mammals and birds, blood volume is most strictly regulated in aquatic teleost
      fishes. Consistently, while an increase in plasma osmolarity (cellular
      dehydration) is a major dipsogenic stimulus for birds and mammals, hypovolemia
      (extracellular dehydration) is a much stronger stimulus for elicitation of
      drinking in teleost fishes. Furthermore, fish cells in culture are tolerant to
      changes in environmental osmolarity compared with mammalian cells, further
      suggesting a secondary role of plasma osmolarity as a target of regulation in
      fishes. A secondary role of blood volume for body fluid regulation in birds is
      further assessed by the fact that volume receptors for thirst, salt gland
      secretion, and vasotocin secretion are localized in the extravascular,
      interstitial space in some species of birds. All terrestrial animals including
      mammals have derived from the fishes in phylogeny, during which the mechanisms
      for body fluid regulation underwent adaptive evolution in the course of
      transition from aquatic to terrestrial life. Therefore, much can be learned from
      comparative studies of body fluid regulation that reveals the diversity and
      uniformity of the mechanisms. In this review, important comparative studies that
      may contribute to an understanding of body fluid regulation throughout vertebrate
      species will be summarized.

PMID- 10880874
TI  - Effects of moderate altitude on exhaled nitric oxide, erythrocytes lipid
      peroxidation and superoxide dismutase levels.
AB  - The purpose of this study was to investigate the effects of staying at a moderate
      altitude (2,300 m, 7 d) on the levels of plasma nitrite, exhaled nitric oxide
      (NO), malondialdehyde (MDA) and superoxide dismutase (SOD). Measurements were
      obtained from 9 female (mean age 18.3 +/- 2) and 9 male (mean age 19.3 +/- 3.7)
      cross-country volunteer skiers: before, during (1st day, 7th day) and after
      staying at a moderate altitude. Exhaled nitric oxide levels were measured only
      before and after staying at the altitude. Nitrite levels increased throughout the
      stay at the altitude, while MDA levels decreased. In parallel with the nitrite
      levels, SOD activities were also found to have increased. Exhaled NO values were
      decreased after the stay at the moderate altitude. These results show that
      altitude hypoxia causes decreased in NO levels in the lung but increased systemic
      NO levels in the blood due to inhibition of erythrocyte lipid peroxidation.

PMID- 10880875
TI  - Effects of removal and reapplication of K(+) and Cl(-) on spontaneous electrical
      activity, slow wave, in the circular muscle of the guinea-pig gastric antrum.
AB  - In the circular muscle of guinea-pig gastric antrum, the effects of removal and
      reapplication of K(+) and Cl(-) were studied on the slow wave, which consists of
      the lower, first and upper, second components. The first component appeared to be
      triggered by the driving potential generated in the interstitial cells. K(+)
      removal slightly depolarized the membrane, increased frequency, and shortened the
      first component and driving potential, and K(+) reapplication hyperpolarized and
      prolonged these potentials transiently. Ouabain abolished the K(+)-induced hyper
      polarization but had no inhibitory effect on the K(+)-induced potentiation. The
      K(+)-induced prolongation was much reduced in Ca(2+)-deficient and increased in
      Ca(2+)-excess solution. BAPTA-AM, thapsigargin, and cyclopiazonic acid shortened
      the slow wave and inhibited the K(+)-induced prolongation but did not block the
      slow wave. Effects of Cl(-) removal were stronger than K(+) removal in shortening
      and increasing the frequency. In Cl(-)-deficient solution, no prolongation was
      observed on K(+) reapplication. Although no conclusive evidence was obtained as
      to the ionic mechanism involved in the effects of K(+) or Cl(-) removal and
      reapplication, a possibility is considered that the sarcoplasmic reticulum is
      involved in determining the duration of the driving potential and the first
      component of the slow wave.

PMID- 10880876
TI  - Excess CO(2) output response during and after short-term intensive exercise in
      sprinters and long-distance runners.
AB  - The purpose of the present study was to examine the response of excess CO(2)
      output to short-term intensive exercise in sprinters (SPR) and long-distance
      runners (LDR). End-tidal CO(2) pressure (PETCO(2)) increased up to about 20 s
      postexercise and then returned to the resting level at about 2-3 min
      postexercise. Thereafter, PETCO(2) remained below the resting level. VCO(2)
      excess, defined as the difference between VCO(2) and VO(2) was integrated from
      the start of exercise until PETCO(2) returned to the resting level. This
      integrated VCO(2) excess was defined as the first phase of CO(2) excess (1st
      CO(2) excess). The subsequent integrated VCO(2) excess until 10 min postexercise
      was defined as the second phase of CO(2) excess (2nd CO(2) excess). The ratio of
      1st CO(2) excess to the lactate rise from rest to the peak value was
      significantly lower in SPR than in LDR, whereas 2nd CO(2) excess was
      significantly greater in SPR than in LDR. The decrease in PETCO(2) at 10 min
      postexercise was significantly larger in SPR than in LDR. The 2nd CO(2) excess
      was closely related to the decrease in PETCO(2). The results in the second phase
      suggest that the difference in the response of excess CO(2) output is derived
      from the difference in the respiratory chemosensitivity to lactic acid rise.

PMID- 10880877
TI  - Involvement of Ca(2+) in antiarrhythmic effect of ischemic preconditioning in
      isolated rat heart.
AB  - We investigated the relationship between the effects of ischemic preconditioning
      (IPC) and Ca(2+) preconditioning (CPC) on reperfusion-induced arrhythmias. In the
      control group (noPC), Langendorff-perfused rat hearts were subjected to 5-min
      zero-flow global ischemia (I) followed by 15-min reperfusion (I/R). In ischemic
      preconditioning groups (IPC), the hearts were subjected to three cycles of 3-min
      global ischemia and 5-min reperfusion. In the CPC group, the hearts were exposed
      to three cycles of 3-min perfusion of higher Ca(2+) (2.3 mmol/l Ca(2+)) followed
      by 5-min perfusion of normal 1.3 mmol/l Ca(2+), and the hearts were then
      subjected to I/R. Verapamil was administered in several hearts of the IPC group
      (VR+IPC). Ventricular arrhythmias upon reperfusion were less frequently seen in
      the IPC and CPC groups than in the noPC and VR+IPC groups. IPC and CPC could
      attenuate conduction delay and enhance shortening of the monophasic action
      potential duration during ischemia. The ventricular fibrillation threshold
      measured at 1-min reperfusion was significantly higher in the IPC and CPC groups
      than in the noPC and VR+IPC groups. Verapamil completely abolished the salutary
      effects of IPC. These results demonstrate that Ca(2+) plays an important role in
      the antiarrhythmic effect of IPC during reperfusion.

PMID- 10880878
TI  - Activation of transepithelial ion transport by secretin in human intestinal Caco
      2 cells.
AB  - Secretin stimulates bicarbonate secretion from pancreatic duct cells, but what
      influence secretin exerts on intestinal tissues remains to be clarified. The aim
      of this study is to examine effects of secretin on ion transport in intestinal
      epithelial Caco-2 cells. We mounted monolayers of Caco-2 cells grown on permeable
      supports for 21-28 d in a Ussing chamber and measured short-circuit currents
      (I(sc)). Addition of secretin (5-100 nM) to the basolateral solution dose
      dependently induced biphasic increases of I(sc) (transient and sustained phase).
      Dibutyryl cyclic AMP (200 microM), forskolin (10 microM), and 3-isobutyl-1
      methylxanthine (IBMX, 1 mM) also induced I(sc) responses similar to the
      administration of secretin. Addition of 5-nitro-2-(3-phenylpropylamino) benzoic
      acid (NPPB, 100 microM) or benzamil (100 microM) to the apical solution markedly
      reduced the secretin-induced I(sc) increase in the transient phase. A selective
      antagonist of cAMP-dependent protein kinase (PKA), N-[2-(p
      bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89, 1 microM), and a
      membrane permeable Ca(2+) chelator, 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA/AM, 10 microM) reduced the
      secretin-induced I(sc). Basolateral addition of 4, 4'-diisothiocyanostilbene-2,2'
      disulfonic acid (DIDS, 1 mM) suppressed the sustained phase I(sc) increase.
      Secretin also induced alkalinization of the apical solution (DeltapH, 0.053 +/-
      0.013). The alkalinization did not occur when DIDS (1 mM) was added to the
      basolateral solution or Na(+) was removed from the solutions. Taken together, our
      observations suggest: (1) secretin stimulates a benzamil-sensitive Na(+) influx
      and an NPPB-sensitive Cl(-) efflux across the apical membrane through PKA
      dependent and Ca(2+)-sensitive pathways; and (2) secretin also induces
      alkalinization of the apical solution through the activation of a DIDS-sensitive
      Na(+)-HCO(3)(-) cotransport in the basolateral membrane of Caco-2 cells.

PMID- 10880879
TI  - Hemodynamic responses to hypoxia and hypercapnia during acute normovolemic
      hemodilution in anesthetized cats.
AB  - The present study was undertaken to evaluate the effects of hypoxia and
      hypercapnia on circulatory parameters during acute normovolemic hemodilution.
      Cats anesthetized with a mixture of alpha-chloralose and urethane were maintained
      by positive pressure ventilation. Muscles were paralysed by intramuscular
      vecuronium (0.1 mg/kg) to eliminate reflex respiratory movements. Cats were
      exposed to hypoxia (12% O(2) and 7% O(2)) and hypercapnia (4% CO(2) and 7% CO(2))
      at normal hematocrit (Ht 40.1 +/- 2.8%) and then at graded levels of normovolemic
      hemodilution (Ht 24.0 +/- 2.0% and Ht 13.0 +/- 1.5%, respectively). Left
      ventricular pressure (LVP), LV dP/dt(max), arterial blood pressure (ABP), heart
      rate (HR), and right atrial pressure (RAP) were recorded on a polygraph. Cardiac
      output (CO) was measured using a cardiac output computer. Hemodilution per se did
      not produce any significant change in ABP, RAP or LV dP/dt(max), however, it
      produced a significant rise in HR and a significant fall in total peripheral
      resistance (TPR). Exposure to hypoxic gas mixtures caused significant increases
      in HR and CO at control Ht; but after hemodilution it caused the reverse effects.
      Hypercapnia did not produce any significant effect on ABP, LV dP/dt(max) or RAP
      either at control Ht or after hemodilution. Hypercapnia produced a fall in HR, CO
      and stroke volume (SV) at normal Ht and percent fall in HR response was enhanced
      following hemodilution. The reversal of chronotropic response to hypoxia and
      enhanced bradycardia response to hypercapnia, under conditions of acute
      normovolemic hemodilution would be deleterious as the tissues would become more
      hypoxic. Such a response may be attributed to altered control mechanisms under
      such conditions of severe stress.

PMID- 10880880
TI  - Receptor-mediated facilitation of cell volume regulation by swelling-induced ATP
      release in human epithelial cells.
AB  - Osmotic swelling induces the release of intracellular ATP in a number of cell
      types. In the immediate vicinity of the cell surface, released ATP has been shown
      to reach a concentration high enough to stimulate P2-purinergic receptors in a
      human epithelial cell line, Intestine 407. The role of released ATP in the
      regulatory volume decrease (RVD) after cell swelling was thus studied in
      Intestine 407 cells. The RVD was suppressed by an ATP hydrolyzing enzyme,
      apyrase, or by a purinergic receptor antagonist, suramin. Extracellular
      application of ATP accelerated the RVD rate in a concentration-dependent manner.
      An increase in the cytosolic free-Ca(2+) concentration was induced by a hypotonic
      challenge, and the swelling-induced Ca(2+) response was partially suppressed by
      apyrase or suramin. A rise in cytosolic Ca(2+) was also induced by extracellular
      application of ATP or UTP, but not ADP, 2-methylthio-ATP or alpha,beta-methylene
      ATP. The ATP-induced Ca(2+) response was blocked by suramin. Therefore, it is
      concluded that RVD is facilitated by ATP, which is released upon cell swelling,
      by augmenting intracellular Ca(2+) rise via the stimulation of purinergic
      (P2Y(2)) receptors in the human epithelial cell.

PMID- 10880881
TI  - Inhibitory effect of central calcitonin-gene related peptide (CGRP) on pancreatic
      secretion in conscious rats.
AB  - The inhibitory effect of central administration of calcitonin-gene related
      peptide (CGRP) on pancreatic secretion stimulated by bile-pancreatic juice
      diversion was determined in conscious rats. Rats were prepared with separate
      cannulae for draining bile and pancreatic juice and with a duodenal cannula and
      an extrajugular vein cannula. In addition, another cannula was stereotactically
      implanted into the left lateral cerebral ventricle. Rats were placed in restraint
      cages and experiments were conducted 4 d after the operation without anesthesia.
      An injection of CGRP (1 nmol/10 microl) into the left lateral cerebral ventricle
      (i.c.v.) inhibited pancreatic secretion as well as cholecystokinin (CCK) release
      induced by bile-pancreatic juice diversion. Intravenous infusion of alpha- and
      beta-adrenergic receptor antagonist, phentolamine and propranolol did not reverse
      the inhibition of pancreatic secretion. Intravenous infusion of CGRP did not
      affect pancreatic secretion or plasma CCK concentrations. The inhibitory action
      of central CGRP (i. c.v.) on pancreatic secretion and CCK release stimulated by
      bile-pancreatic juice diversion is partially mediated by an alpha-adrenergic
      mechanism, although its precise mechanism has not been elucidated.

PMID- 10880882
TI  - Regulation of inwardly rectifying K(+) channel in cultured opossum proximal
      tubule cells by protein phosphatases 1 and 2A.
AB  - The inwardly rectifying ATP-regulated K(+) channel with an inward conductance of
      about 90 pS in the surface membrane of cultured opossum kidney proximal tubule
      (OKP) cells is activated at least in part by protein kinase A (PKA). In this
      study, we examined the effects of protein serine/threonine phosphatase types 1
      (PP-1) and 2A (PP-2A) on activity of the K(+) channel using the patch-clamp
      technique. In cell-attached patches, channel activity was enhanced by the
      application of okadaic acid (OA, 1 microM), a membrane-permeable inhibitor of PP
      1 and PP-2A, to the bath solution. This enhancement was abolished by the
      pretreatment of cells with KT5720 (200 nM), a specific inhibitor of PKA. In
      inside-out patches, channel activity which could be maintained in the presence of
      ATP (3 mM) in the bath solution was also increased by the addition of OA (1
      microM), and the OA-induced increase in channel activity was partially prevented
      in the presence of KT5720 (200 nM). Direct application of either PP-1 (1 U/ml) or
      PP-2A (1 U/ml) to the cytoplasmic surface of the patch membrane inhibited channel
      activity maintained by ATP (3 mM) in inside-out patches. Moreover, channel
      activity stimulated by PKA (20 nM) in the presence of ATP (3 mM) was also
      inhibited by the application of either PP-1 (1 U/ml) or PP-2A (1 U/ml). These
      results indicate that the OA-sensitive protein phosphatase is involved in the
      regulation of channel activity, and suggest that both PP-1 and PP-2A are
      candidates responsible for the inhibition of channel activity through
      dephosphorylation of the PKA-mediated protein phosphorylation.

PMID- 10880883
TI  - Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left
      ventricle.
AB  - Caffeine causes a considerable O(2) waste for positive inotropism in myocardium
      by complex pharmacological mechanisms. However, no quantitative study has yet
      characterized the mechanoenergetics of caffeine, particularly its O(2) cost of
      contractility in the E(max)-PVA-VO(2) framework. Here, E(max) is an index of
      ventricular contractility, PVA is a measure of total mechanical energy generated
      by ventricular contraction, and VO(2) is O(2) consumption of ventricular
      contraction. The E(max)-PVA-VO(2) framework proved to be powerful in cardiac
      mechanoenergetics. We therefore studied the effects of intracoronary caffeine at
      concentrations lower than 1 mmol/l on left ventricular (LV) E(max) and VO(2) for
      excitation-contraction (E-C) coupling in the excised cross-circulated canine
      heart. We enhanced LV E(max) by intracoronary infusion of caffeine after beta
      blockade with propranolol and compared this effect with that of calcium. We
      obtained the relation between LV VO(2) and PVA with E(max) as a parameter. We
      then calculated the VO(2) for the E-C coupling by subtracting VO(2) under KCl
      arrest from the PVA-independent (or zero-PVA) VO(2) and the O(2) cost of E(max)
      as the slope of the E-C coupling VO(2)-E(max) relation. We found that this cost
      was 40% greater on average for caffeine than for calcium. This result, for the
      first time, characterized integratively cardiac mechanoenergetics of the O(2)
      wasting effect of the complex inotropic mechanisms of intracoronary caffeine at
      concentrations lower than 1 mmol/l in a beating whole heart.

PMID- 10880884
TI  - Effects of corticosteroids on synaptic transmission in rat dorsolateral septal
      nucleus.
AB  - The effects of corticosteroids on synaptic transmission in the rat dorsolateral
      septal nucleus (DLSN) were examined, in vitro, by using intracellular and voltage
      clamp recording methods. Prednisolone (100 microM) increased the amplitude of
      excitatory postsynaptic potential (EPSP) and depressed both fast and slow
      inhibitory postsynaptic potentials (IPSP). Under voltage-clamp conditions,
      prednisolone (100 microM) increased the amplitude of excitatory postsynaptic
      current (EPSC) and depressed the fast and slow inhibitory postsynaptic currents
      (IPSCs). Corticosterone (100 microM) mimicked the effects of prednisolone on the
      postsynaptic currents (PSCs). To examine the direct effects of prednisolone on
      the EPSC and slow IPSC, the fast IPSC was blocked by bicuculline (20 microM).
      Under these experimental conditions, prednisolone (100 microM) did not alter the
      isolated EPSC but depressed slow IPSC by 22 +/- 3% (n = 10). The fast IPSC was
      isolated by pretreatment with kynurenic acid and CGP55845A, where the EPSC and
      slow IPSC were blocked. Prednisolone (100 microM) depressed the isolated fast
      IPSC in DLSN neurons. Prednisolone (100 microM) did not change either the inward
      current produced by glutamate or the outward current produced by gamma
      aminobutyric acid (GABA). The results suggest that corticosteroids facilitate
      excitatory synaptic transmission in the DLSN by reducing the release of GABA from
      the presynaptic nerve terminals of interneurons.

PMID- 10880885
TI  - The biomechanic origin of sprint performance enhancement after one-week creatine
      supplementation.
AB  - In order to test whether an improvement of maximal sprinting speed after creatine
      (Cr) supplementation was due to the increase of stride frequency (SF), stride
      length (SL) or both, 7 subjects ran 4 consecutive sprints after 1 week of placebo
      or Cr supplementation. SF and SL were assessed by a triaxial accelerometer.
      Compared to the placebo, Cr induced an increase of running speed (+1.4% p < 0.05)
      and SF (+1.5%, p < 0.01), but not of SL. The drop in performance following
      repeated sprints was partially prevented by Cr. In conclusion, exogenous Cr
      enhanced sprinting performance by increasing SF. This result may be related to
      the recent findings of shortening in muscular relaxation time after Cr
      supplementation.

PMID- 10880886
TI  - Volume expansion sensitivity of swelling-activated Cl(-) channel in human
      epithelial cells.
AB  - In human epithelial cell lines, whole-cell swelling-activated Cl(-) current was
      not directly correlated to cell volume per se, membrane tension or hydrostatic
      pressure. The current density exhibited a relation described by a Boltzmann
      function to the square of the cell diameter. Cytochalasin D enhanced the volume
      sensitivity. These results suggest that the activation mechanism of volume
      sensitive Cl(-) channel is related to cytoskeleton-dependent membrane spring
      energy in human epithelial cells.

PMID- 10880887
TI  - A semi-quantitative PCR method for the detection of low levels of apoptotic DNA
      fragmentation in a heart failure model.
AB  - Cells that are apoptotic and comprise less than 2% of the total cellular
      population are difficult to detect by conventional methods (i.e., DNA ladder). We
      discuss a new methodological technique, PCR-amplified DNA ladder, to detect very
      low levels of DNA fragmentation (indicative of apoptosis) in a myocardial infarct
      heart failure model. Results and methodology are contrasted with the traditional
      DNA ladder technique.

PMID- 10880888
TI  - Correlation between erythropoietin and lactate in humans during altitude
      exposure.
AB  - The plasma concentrations of both immunoreactive erythropoietin (EPO) and lactate
      were determined in four healthy untrained subjects at sea level and on the 2nd or
      3rd day at altitudes (1,300 and 3,500 m). The mean plasma EPO (18.8 +/- 1.6 mU/ml
      at sea level) increased significantly on the 3rd day at 1,300 m (25.5 +/- 2.0
      mU/ml, p < 0. 05) and showed an almost three-fold increase on the 2nd day at
      3,500 m (53.5 +/- 3.7 mU/ml, p < 0.001). Likewise, the mean plasma lactate at
      3,500 m (3.98 +/- 0.27 mmol/l) was 3.6 times as high as that at sea level (1.11
      +/- 0.05 mmol/l) (p < 0.001). The plasma EPO concentrations were found to
      correlate well with the lactate concentrations at sea level and altitudes (r =
      0.86, p < 0.01). These results are consistent with the well-known EPO/lactate
      response to altitudes and suggest that the circulating EPO concentration as well
      as blood lactate concentration can be used as an index of anaerobic condition.

PMID- 10880889
TI  - Consequences of the diabetic status on the oxidant/antioxidant balance.
AB  - It has been shown that elevated extra- and intra-cellular glucose concentrations
      result in an oxidative stress, which is defined as an imbalance between
      prooxidants and antioxidants. Several mechanisms seem to be involved in the
      genesis of this oxidative stress, which has been reported both in experimental
      diabetes in animals and in type 1 and type 2 diabetic patients: glucose
      autoxidation, protein glycation and formation of advanced glycation endproducts,
      and the polyol pathway. Reciprocally, oxidative stress is involved in the origin
      of type 1 diabetes, especially via the apoptosis of pancreatic beta-cells, as
      well as insulin resistance in type 2 diabetes. Glucose control plays an important
      role in the prooxidant/antioxidant balance. Macromolecules such as molecules of
      extracellular matrix, lipoproteins and deoxyribonucleic acid are also damaged by
      free radicals in diabetes mellitus. A supplementation with antioxidants has been
      proposed as a complementary treatment, and some antidiabetic agents may by
      themselves have antioxidant properties independently of their role on glucose
      control. The aim of this paper was to review the consequences of the diabetic
      status on the oxidant/antioxidant balance.

PMID- 10880890
TI  - Plasma levels of tumor necrosis factor-alpha (TNF-alpha) are essentially
      dependent on visceral fat amount in type 2 diabetic patients.
AB  - TNF-alpha is considered as one of the potential determinants of insulin
      resistance. However several data suggest that TNF-alpha expression itself, could
      be modulated by the degree of adiposity and/or plasma insulin levels. To clarify
      the determinants of plasma TNF-alpha levels in type 2 diabetes mellitus, we
      studied the impact of intensive insulin treatment on plasma TNF-alpha levels in
      16 type 2 diabetic subjects with failure to oral antidiabetic medication (HbA1c:
      10.8 +/- 1.2 %). Furthermore, we analyzed the relationship between plasma TNF
      alpha levels and total or regional body fat measurements using anthropometry,
      bienergetic absorptiometry and computed tomography in a cohort of 33 caucasian
      obese type 2 diabetic subjects (BMI: 32.2 +/- 4.4 kg/m(2) ). The plasma TNF-alpha
      level was neither affected by plasma glucose level variations nor intensive
      insulin treatment despite a 37 % decrease in daily insulin needs at the end of
      insulin therapy (total duration: 11.5 +/- 2.0 days). The plasma TNF-alpha level
      was similar in men and women and unrelated to age, fasting glycemia or HbA1c. A
      relationship was highlighted with BMI (r =0.39, p <0.02), but not with total fat
      mass. This relationship was only dependent on the intra-abdominal fat mass amount
      as assessed by the waist-to-hip circumference ratio (r =0.52, p <0.01) and the
      visceral adipose tissue area (r =0.56, p <0. 01). These results show that plasma
      TNF-alpha levels are essentially dependent on visceral fat amount, thus
      suggesting that TNF-alpha could be one of the factors mediating insulin
      resistance and cardiovascular risk in obese type 2 diabetic patients.

PMID- 10880891
TI  - Efficacy and safety of micronised fenofibrate in a randomised double-blind study
      comparing four doses from 200 mg to 400 mg daily with placebo in patients with
      hypercholesterolemia.
AB  - The aim of this study was to evaluate the efficacy on LDL-cholesterol (LDL-C) of
      micronised fenofibrate given for three months at doses ranging from 200 to 400 mg
      once daily, compared with placebo. A double-blind, randomised, parallel-group,
      multi-centre trial was performed in four centers of France in 340
      hypercholesterolemic patients (163M, 177F) aged 18-75 years. After a 2-3 month
      single-blind run-in period on placebo and diet, patients with LDL-C greater than
      or equal to 4.65 mmol/l (180 mg/dl) maintained on the same diet throughout the
      study were randomly allocated to placebo or to 200, 267, 340 or 400 mg micronised
      fenofibrate, given once daily with the evening meal for 3 months. LDL-C, total
      cholesterol (TC), total triglycerides (TG) and apolipoprotein B (Apo B)
      significantly decreased compared with placebo in all four fenofibrate groups. For
      all randomised patients, the decrease in the fenofibrate groups ranged from 31.6
      38.8% for LDL-C, 24.5-31.9% for TC, 26.7-40.8% for TG, and 27.3-35.0% for Apo B.
      An increase in HDL-cholesterol of 4.1-8.2% was observed in the fenofibrate
      groups, but did not reach statistical significance. Lipid values in the placebo
      group remained unchanged. The therapeutic goal of LDL-C<3.36 mmol/l (130 mg/dl)
      was reached in 27% in the 200 mg group and increased to 56% in the 300 mg group.
      There were no major clinical or biological adverse events in the dose interval
      from 200 mg to 400 mg of micronised fenofibrate per day. This study showed
      treatment for 3 months with micronised fenofibrate at doses up to 400 mg per day
      is effective and can reduce LDL-cholesterol up to 30% allowing further evaluation
      of these doses on longer trials.

PMID- 10880892
TI  - Improved blood glucose variability, HbA1c insuman Infusat and less insulin
      requirement in IDDM patients using insulin lispro in CSII. The Swedish
      Multicenter Lispro Insulin Study.
AB  - The aim of the study was to compare lispro (LP) and Insuman(R) (I) insulin in
      continuous subcutaneous insulin infusion (CSII) therapy with respect to blood
      glucose control as expressed by the standard deviation of blood glucose (SD(BG) )
      and HbA(1c) and to monitor the well-being (WBQ) and treatment satisfaction (DTSQ)
      parameters during such treatment. Forty-one IDDM patients who had used CSII for
      at least 6 months participated in an open-label, randomized, cross-over,
      multicenter study for 4 months (2 months LP and 2 months I or vice versa).
      Boluses with LP were given 5 min before each meal and with I 30 min before each
      meal. During LP administration compared with I, the SD(BG) of all blood glucose
      values (3.6 mmol/l vs. 3.9 mmol/l, p=0.012), as well as the SD(BG) of the
      postprandial, blood glucose values (3.6 mmol/l vs. 4.0 mmol/l, p=0.006), were
      significantly reduced. The HbA(1c) was significantly lower during LP
      administration (7.4% vs. 7.6%, p=0.047). The incidence of hypoglycemic events per
      30 days (capillary blood glucose<3.0 mmol/l and/or symptoms) did not
      significantly differ between LP and I (9.7 vs. 8.0 per month, p=0.23). The total
      amount of daily insulin was slightly but significantly lower with LP, compared to
      I (38.0 IU vs. 40.3 IU, p=0.004). There was no treatment effects of LP compared
      to I concerning WBQ and DTSQ. It is concluded that in CSII therapy LP is superior
      to I with respect to the stability of blood glucose control, a lower HbA(1c), a
      less insulin requirement without increasing the frequency of hypoglycemia.

PMID- 10880893
TI  - Insulin treatment with preprandial injections of regular insulin in middle-aged
      type 2 diabetic patients. A two years observational study.
AB  - AIMS: To describe effectivity and safety variables in Type 2 diabetic patients on
      preprandial regular insulin therapy before each main meal (supplementary insulin
      therapy SIT) during an observational period. METHODS: A group of 77 consecutive
      Type 2 diabetic patients in whom SIT was initiated at this department between
      January 1994 and March 1998 were subjected to a follow-up examination after a
      mean of two years during which time they were mainly cared for by their family
      physicians. RESULTS: For 86 % patients (n =66) the continuation of SIT was
      documented; in 41 % of them (n =27) a bed time injection of NPH insulin was added
      in order to adequately control fasting glycaemia. HbA1c had fallen from 9.3 +/
      1.8 to 7.4 +/-1.7 %; no episode of major hypoglycaemia occurred; there was no
      statistically significant increase in body weight. CONCLUSIONS: This
      observational study describes favourable intermediate outcome parameters of
      effectivity and safety for prandial regular insulin therapy of Type 2 diabetic
      patients, such as lowering of HbA1c without occurrence of major hypoglycaemia and
      without weight gain. Controlled trials are needed to confirm the encouraging
      results from this pilot study.

PMID- 10880894
TI  - In vivo measurement of gluconeogenesis in animals and humans with deuterated
      water: a simplified method.
AB  - The contribution of gluconeogenesis to glucose production can be measured by
      comparing after ingestion of deuterated water the enrichment in deuterium of the
      hydrogen bound to carbon 5 of glucose with that of hydrogen bound to carbon 2 or
      with the deuterium enrichment of plasma water. The method developed by Landau et
      al. for measuring deuterium enrichment on carbon 5 by gas chromatography-mass
      spectrometry analysis is tedious and time consuming. We developed a simpler
      procedure for measuring this deuterium enrichment. Deuterium enrichment on
      carbons 5 and 6 of glucose is measured using the 1,2-5, 6-diisopropylidene-3-O
      acetyl-a-furanosyl derivative. Enrichment in position 6 is measured using the
      hexamethylenetetramine procedure and subtracted from the enrichment on carbons 5
      and 6 to obtain the specific enrichment on carbon 5. We tested first this method
      in post-absorptive and fasted rats (plasma water enrichment 0.6%) infused
      simultaneously with [6,6-(2) H(2) ] glucose in order to obtain not only the
      percent contribution of gluconeogenesis, but also glucose turnover rate and
      absolute gluconeogenesis flux. In post-absorptive and starved rats
      gluconeogenesis represented respectively 46.7+/-2.0% and 94.1+/-2.0% of glucose
      production and a flux of 31.1+/-1.8 and 38.9+/-0.9 micromol/kg/min. The method
      was then used in humans. The contribution in the post-absorptive state of
      gluconeogenesis to glucose appearance measured in control and type 2 diabetic
      subjects (plasma water enrichment 0.23-0.38%) was 40. 7+/-5.0% and 65.7 +/-3.3%
      (p<0.05) respectively. In conclusion this simplified method appears useful for in
      vivo studies of gluconeogenesis.

PMID- 10880895
TI  - Glucose profiles in a type 1 diabetic patient successively treated with CSII
      using regular insulin, lispro and an implantable insulin pump.
AB  - The delayed subcutaneous insulin absorption makes stable blood glucose difficult
      to achieve in patients with type 1 diabetes, and there is a high risk for severe
      hypoglycemia. The human insulin analogs demonstrated to circumvent this major
      limitation of rapid-acting insulin particularly in the context of a continuous
      subcutaneous insulin infusion (CSII). As insulin profiles generated by
      implantable insulin pump (IP) are similar to lispro, we studied glucose profiles
      and the risk for severe hypoglycemia assessed by the low blood glucose index
      (LBGI) in a patient successively moved from CSII using regular-acting insulin to
      CSII using lispro and finally to an IP. Insulin delivery with the IP, and to a
      lesser extent CSII using lispro tend to reduce the average glycemia in comparison
      with CSII using regular-acting insulin (114.2+/-53.0, 131. 6+/-56.8 and 140.7+/
      81.5 mg/dl, respectively). Reduction of glycemic fluctuations assessed by area
      under the curves was more pronounced during IP therapy in comparison with lispro
      and with rapid-acting insulin in CSII (789.5, 798.2 and 891.5 h.mg.dl-1,
      respectively). LBGI remained in the moderate range with IP and CSII using lispro
      (4.3+/-6.8 and 4.0+/-5.7 respectively), while LBGI was in the high range with
      rapid-acting insulin (5.5+/-10.2). In conclusion our case report suggests that IP
      tends to reduce the average glycemia and affect the amplitude of glycemic
      fluctuations in comparison with CSII using lispro, with an equivalent risk for
      severe hypoglycemia. A prospective randomized study is needed to compare these
      two modes of insulin replacement.

PMID- 10880896
TI  - Evidence of recurrent type I diabetes following HLA-mismatched pancreas
      transplantation.
AB  - Type 1 diabetes mellitus is considered as an autoimmune disease against beta
      cells. Diabetes recurrence after pancreas transplantation is well known in HLA
      identical twins while it is rarely reported in recipients of cadaveric pancreatic
      grafts. In the present case report, diabetes recurrence occurred in a recipient
      who underwent cadaveric combined pancreas kidney transplantation. Seven years
      after transplantation the patient exhibited progressive hyperglycemia needing
      insulin therapy while the renal graft was well functioning. The diagnosis of
      recurrent disease was obtained on the histological features such as selective
      loss of beta cells without clear signs of insulitis and on the presence of
      markers (GAD 65 and IA-2) for humoral autoimmunity. It is intriguing that, at the
      time of recurrence of type 1 diabetes, the patient had stopped steroids and
      azathioprine, while only cyclosporine was maintained as immunosuppressive
      treatment. Our case report underlines the relevance of studying the humoral
      autoimmune response directed to islet autoantigens in cadaveric pancreas
      allograft recipients. Furthermore, it suggests that an efficient
      immunosuppressive treatment after transplantation may be able to reduce the
      autoimmune response against the pancreatic allograft.

PMID- 10880897
TI  - [Role of antibiotic therapy in diabetic foot management].
AB  - Antibiotic therapy is not the most important component in diabetic foot ulcer
      management which should be based on weight bearing avoidance and arterial
      revascularization. However antibiotic therapy is necessary in presence of
      extensive deep involvement or systemic signs of infection. Initial antimicrobial
      treatment depends on bacteria supposed origin. For patients not coming from
      hospital, the initial choice antibiotic is an amoxicillin/clavulanate agent
      because it offers optimal coverage for most pathogens involved in those diabetic
      foot lesions (gram positive cocci, gram negative and anaerobic organisms). For
      patients at high risk to be infected with nosocomially acquired pathogens, the
      initial antibiotic therapy must cover methicillin-resistant staphylococci,
      resistant pseudomonas aeruginosa or enterobacteriae. In all cases, when
      definitive reliable cultures are reported, initial antibiotic regimens should be
      revised to narrow the coverage to specific pathogens. In presence of
      osteomyelitis, a temporary combination of two agents which are known to reach
      high bone concentrations is necessary, and antibiotic therapy should be continued
      for at least two months. In other cases, antibiotic treatment duration depends on
      clinical out come.

PMID- 10880898
TI  - [Medical resources consumption of type 2 diabetics in France in 1998].
AB  - The research objective of CODE-2 study was to estimate the total direct medical
      resources use of type 2 diabetes in France and in Europe. Only French data are
      provided in this paper. Total medical resources consumption of type 2 diabetics
      on a 6 months retrospective period were collected through a national practitioner
      survey (including both general practitioners and diabetology/endocrinology
      specialists). This survey was completed for 751 patients. Data collected were
      then extrapolated to be representative of all type 2 diabetics in France. Average
      medical resources consumption of a type 2 diabetic per year is 3 350 US$ (1 US$
      =6FF). This figure is a minimum because some costs were underestimated in the
      study. Extrapolated to all diagnosed and treated type 2 diabetics in France, this
      expenditure is 4.3 billion US$ and accounts for 3.8 % of the total medical
      resources consumption in France (prevalence of type 2 diabetes reaches 2.5 % in
      the general population). Among this consumption, 24.1 % is directly related to
      diabetes, 26.7 % to potential related diabetes complications and 49.2 % to other
      diseases. Time since diagnosis, current treatment type and complications are the
      main factors which increase such consumption. CODE-2 study reveals the high level
      of medical resources consumption associated with type 2 diabetes complication. It
      confirms that more efficient therapeutical strategies are needed to avoid these
      complications.

PMID- 10880899
TI  - [Strategy for patient management with type 2 diabetes excepting care of
      complications. Recommendations of ANAES--March 2000].

PMID- 10880911
TI  - [Not Available].

PMID- 10880912
TI  - [How to detect Helicobacter pylori before and after eradication treatment?].

PMID- 10880913
TI  - [How to eradicate Helicobacter pylori?].

PMID- 10880914
TI  - [Management of complicated and non complicated gastric and duodenal ulcer
      disease].

PMID- 10880915
TI  - [Should Helicobacter pylori infection be taken into account in the use of
      nonsteroidal anti-inflammatory agents?].

PMID- 10880917
TI  - [Should Helicobacter pylori infection be considered in the management of
      dyspeptic patients?].

PMID- 10880916
TI  - [Should Helicobacter pylori infection be considered in patients with gastro
      esophageal reflux?].

PMID- 10880918
TI  - [Consensus development conference on Helicobacter pylori. Revised conclusions and
      recommendations of the Working group (1999)].

PMID- 10880919
TI  - [Optic neuropathy after proton-beam therapy for malignant choroidal melanoma].
AB  - Proton-beam irradiation is a conservative therapy commonly used for the treatment
      of uveal malignant melanomas. Some adverse effects such as optic neuropathy can
      compromise the visual outcome. We were interested in determining the risk factors
      for radiation papillopathy. Since there is currently no effective therapy, this
      is an interesting way to improve prevention of optic neuropathy. Six hundred
      sixty-two eyes had more than 24 month follow-up after proton-beam irradiation for
      uveal melanoma. In five hundred twenty-two cases, the clinical examination of the
      optic nerve head by ophthalmoscopy was possible. One-hundred eleven optic discs
      were pathologic, whereas 411 remained disease-free. Retrospective study of these
      two groups allowed to quantify the risk factors for optic neuropathy. The
      irradiation of more than 2mm of optic nerve at 30 Grays-equivalents appeared to
      be the major risk factor for optic neuropathy. For a given irradiation dose, the
      observed pattern of clinical responses was heterogeneous. These results are
      discussed and compared to the previous published reports. Visual results and life
      prognosis are also discussed, considering the optic nerve head status. Proton
      beam therapy can preserve the optic nerve when the tumor location allows to keep
      it away from the irradiation-field. Patients must be informed about the risk of
      optic neuropathy after proton-beam irradiation.

PMID- 10880920
TI  - [Indomethacin (indocollyre) versus diclofenac (voltarene) for the control of pain
      following excimer photoablation].
AB  - PURPOSE: To compare effect of two topical non steroidal anti-inflammatory (NSAI)
      drugs: Indomethacin (Indocollyre)0.1 %, Chauvin Inc.) and Diclofenac (Voltaren
      0.1%, Cibavision) on postoperative pain and epithelial regrowth following surface
      excimer photoablation. MATERIAL AND METHOD: Eighty-six excimer operated patients,
      were divided in two similar groups depending on the NSAI instilled
      postoperatively and for 3 days (4 drops daily). No patient was informed of any
      other available drug. Pain intensity was quantified between 1 and 10 according to
      an analog scale (reported from 1 to 10 hours, then 4 times a day during 7 days).
      Complementary medications and functional symptoms were also notified.
      Biomicroscopic evaluation using fluorescein test was performed to assess
      reepithelialization. RESULTS: In term of pain, no significative difference was
      observed between the two groups concerning intensity, associated medications, or
      numbers of days of discomfort. Controversially, retreated eyes might induce more
      pain than initial treatments. No delay in epithelial regrowth was noted and the
      difference between the two groups in functional complaints was no statistically
      significant. Pain appears to be not related to ablation depth. DISCUSSION-
      CONCLUSION: Our results are correlated to literature reported data. Introduction
      of NSAI constitutes a real advent in the care of excimer postoperative pain.
      Effect of indomethacin seems comparable to diclofenac effect, but might be of
      interest because of no anesthetic property that might guarantee of no delay in
      wound healing response.

PMID- 10880921
TI  - [Trabeculectomy in black Africans in primary open angle glaucoma].
AB  - PURPOSE: To assess simple trabeculectomy in black Africans with open angle
      glaucoma. METHODS: We studied retrospectively 80 eyes of 62 patients with primary
      open angle glaucoma operated by Cairn's trabeculectomy without adjunction of
      antimetabolites. Thirty seven eyes had a limbal-based conjunctival flap and the
      others 43 had a fornix-based conjunctival flap. Failures and success were
      assessed with the Kaplan-Meier's method. RESULTS: Patients were all seen at least
      12 months after surgery. The mean follow up was 24 months. At mid-term survey we
      found complications to be frequent. Pathological blebs occurred in 22.5% (18
      cases). The survival probability grew shorter with time. Only 44% of patients
      were reviewed at 36 months and 29% at 48 months. The success rate (IOP less than
      21 mmHg of all glaucoma medications) varied according to the conjunctival flap.
      It was respectively at 12 months, 24 months and 36 months: 97%, 70 % and 54% with
      limbal-based flap, and 46%, 18% and 18% with fornix-base flap. The overall rate
      of tonometric failures was 33.75%. Failures were more often with fornix- based
      flap (85%). Generally they set in before one year of survey. This was so in 91%
      of absolute failures and in 87% of relative failures. The failures rate seems to
      increase with topical polytherapy given more than 12 months before operation.
      CONCLUSIONS: Trabeculectomy with limbal-based conjunctival flap is at mid-term
      follow up successful in black Africans. However the following up difficulties in
      Africa makes it a too delicate assessment objective for long-term results of
      trabeculectomy.

PMID- 10880922
TI  - [Diagnostic strategy in uveitis: a prospective study in 125 cases].
AB  - BACKGROUND: The diagnosis of uveitis is a difficult one and subject to much
      debate between ophthalmologists and internists. In 1992, we carried out a
      prospective study to assess the importance of the internist's consultation, the
      contribution of an extensive laboratory evaluation and to propose a well
      considered diagnostic strategy. MATERIAL: and methods: From 1992 to 1995, all
      patients seen at consultation at the Grenoble University Hospital had a complete
      ophthalmologic evaluation, an internist's consultation, an extensive laboratory
      evaluation and a follow-up for at least 6 months. RESULTS: One hundred twenty
      five patients were included. The rate of diagnosis was 72%. The internist's help
      was useful in at least 68% of the diagnoses. Laboratory and radiography tests
      provided pertinent information in 77% of the cases. Follow-up allowed finding 11%
      of the diagnoses. The analysis of the clinical and laboratory tests enabled us to
      establish a diagnostic strategy chart where the key pint is clinical and
      ophthalmologic evaluation. A minimal laboratory evaluation systematically
      performed for all cases of uveitis is proposed and, according to some
      characteristics of uveitis, a well-targeted laboratory evaluation is recommended.
      CONCLUSION: This diagnostic strategy enabled establishment of the diagnosis in
      92% of the cases and limited laboratory evaluation for 68 patients. We are
      performing a new prospective study to better validate this diagnostic chart.

PMID- 10880923
TI  - [Translocation of the macula for retrofoveal choroidal neovascularization in age
      related macular degeneration and severe myopia: first results].
AB  - BACKGROUND: Subfoveal choroidal neovascularization is a main cause of blindness.
      The new surgical technique of macular translocation conceived by De Juan, with
      scleral shortening and without a retinotomy, allows to move the fovea away from
      the neovascular membrane with a low rate of complications. The first results
      obtained with this technique are presented here, in cases of submacular
      neovascularization due to age-related macular degeneration (AMD) or degenerative
      myopia. PATIENTS AND METHODS: The first 10 patients who were operated on with
      this technique presented with subfoveal neovascularization due to AMD (6 eyes) or
      myopia (4 eyes). The time period between the beginning of the disease and surgery
      was less than 3 months. Before and after surgery, a complete examination included
      fluorescein and ICG angiographies and OCT. RESULTS: Visual acuity improved by 2
      lines or more in 6 eyes (60%), was unchanged in 3 eyes (30%) and decreased in 1
      eye. The improvement in vision seemed higher in myopia than in ARMD. Conversely,
      the mean foveal displacement was greater in ARMD than in myopia (1.2 disc
      diameter and 0.5 respectively). Laser photocoagulation has been performed in all
      patients after surgery. Main complications were retinal detachment (1 eye) and
      neovascularization at the site of transretinal injection (1 eye). Mean follow-up
      was 3 months. COMMENTS: Macular translocation with the technique described by De
      Juan allowed visual improvement in more than the half of the eyes with subfoveal
      neovascularization, resulting in a moderate rate of complications. Long term
      follow-up is necessary to confirm these results.

PMID- 10880924
TI  - [Orbital fracture with medial rectus entrapment. A case report].
AB  - Orbital fracture can be complicated by medial rectus muscle entrapment which
      usually involves the anterior part of the muscle (pseudo Duane syndrome). We
      describe an unusual case of isolated medial orbital wall fracture with medial
      rectus entrapment. Our patient had entrapment of the posterior part of the muscle
      with exotropia and limitation of adduction. This rare complication must be
      recognized so the appropriate management could be instituted early to avoid
      potential functional sequelae.

PMID- 10880925
TI  - [Ultrastructural findings of epimacular membrane and detached posterior hyaloid
      in vitreomacular traction syndrome].
AB  - PURPOSE: Vitreomacular traction syndrome is characterized by an incomplete
      posterior vitreous detachment and by the cortical vitreous remaining attached to
      the macula. In certain case epimacular membrane is clinically well defined. We
      studied the electron microscopic features of epiretinal tissue and posterior
      hyaloid removed from the posterior pole. MATERIAL AND METHODS: [corrected] Six
      epimacular membranes were removed during a pars plana vitrectomy, placed in 2.5%
      glutaraldehyde solution, embedded in Epoxy resin, and examined in a transmission
      electron microscope. The detached posterior hyaloid was removed and analyzed
      separately in two cases. RESULTS: The analysis disclosed five morphologically
      cell types. Fibrous astrocytes were predominant in five cases. Other cell types
      were less frequent and were identified as fibroblasts, macrophages and
      myofibroblasts. In one case epithelial-like cell type was predominant. The stroma
      was mainly composed of a thin layer of 15-nm diameter collagen evoking a vitreous
      origin. Internal limiting membrane was present in one case only. Detached
      posterior hyaloid was constituted by the same cellular constituents on thin layer
      of vitreous collagen. DISCUSSION: The cellular proliferation is principally
      constituted by fibrous astrocyte and occurs on the inner surface of cortical
      vitreous. Some glial cells seem to present an epithelial differentiation.
      CONCLUSION: The attached and detached posterior hyaloid in vitreomacular traction
      syndrome is the place of glial cells migration and proliferation.

PMID- 10880926
TI  - [Giant basal cell carcinoma of the eyelid in a black patient from Cameroon].
AB  - Basal cell carcinoma of the skin is the most common human cancer. It is also the
      most frequent malignant tumor of the eyelid. In Europe, its most common clinical
      presentation is a hard indurated, and sometimes ulcerated nodule. The authors
      report a giant palpebral basal cell carcinoma in a black non albinos Cameroonian
      patient. The ethnic origin, localization and macroscopic aspect are discussed.
      The problems connected with diagnosis and treatment of malignant tumors in Africa
      are noted.

PMID- 10880927
TI  - [Neovascular glaucoma diagnosed following carotid endarterectomy].
AB  - We report a case of bilateral asymptomatic rebeosis iridis related to a bilateral
      obstruction of the carotid arteries. The iridocorneal angles were closed by a
      neovascular membrane and intraocular pressures were normal within both eyes
      (normotensive neovascular glaucoma). After left carotid endarterectomy, the
      increased perfusion of the ciliary body and the increased secretion of aqueous
      humor resulted in a sudden bilateral ocular hypertension. Management of ocular
      neovascularization related to carotid artery obstruction may involve the
      destruction of areas of retinal ishchemia (laser panretinal photocoagulation or
      cryotherapy) before carotid surgery.

PMID- 10880928
TI  - [Acute closure-angle glaucoma after treatment with ipratropium bromide and
      salbutamol aerosols].
AB  - We report a case of acute angle-closure glaucoma in a patient treated with
      bronchodilator nebulization. An 82-year-old man with chronic obstructive
      bronchopathy was treated for acute respiratory decompensation with salbutamol and
      ipratropium bromide aerosols. Twenty-four hours after beginning the treatment,
      the patient developed acute angle-closure glaucoma which resolved rapidly with
      appropriate treatment. The case emphasizes the importance of precautionary
      measures (waterproof glasses and inhalation masks). In addition patients with a
      high risk of angle-closure glaucoma should be detected prior to prescribing
      bronchodilating aerosols.

PMID- 10880929
TI  - [What strategy after three trabeculectomy failures?].
AB  - Three trabeculectomy failures raises the delicate problem of refractory glaucoma
      with unresponsive ocular hypertony. The therapeutic strategy requires first a
      careful assessment of the reasons for the previous failures (internal or external
      obstacles to filtration which might have responded to preventive treatment),
      then, depending on the patient's age, type of glaucoma, anatomic status of the
      ocular structures and the visual potential of the eye, a choice has to be made
      between different surgical techniques aimed at favoring aqueous humor evacuation
      (trabeculectomy associated with antimetabolites or drainage implant) or
      destruction of the ciliary body to reduce intraocular pressure by limiting the
      production of aqueous humor. Choosing between these two possibilities is not an
      easy task as success rates are highly variable on such eyes and complications are
      frequent, leading to lower visual acuity in 30 % of the cases. These salvage
      procedures recall that first line trabeculectomy must be optimized in all cases.

PMID- 10880930
TI  - [Drainage implant surgery for refractory glaucoma].

PMID- 10880931
TI  - [ [In Process Citation]

PMID- 10880932
TI  - [Unusual preseptal location of an orbital cavernous hemangioma in African
      patient].
AB  - Cavernous hemangioma is the most common primary vascular orbital tumor in adults.
      Generally the benign tumor arises within the muscle cone, revealed by proptosis
      with choroidal folds, and more rarely develops in other orbital localizations. We
      report the case of a 42-year-old female African patient who had a cavernous
      hemangioma in an unusual anterior localization. Clinically, a small superficial
      tumor was palpated in the right superior nasal orbital angle. After complete
      surgical excision, the histopathological study established the diagnosis of
      cavernous hemangioma

PMID- 10880933
TI  - [Postoperative compressive spinal epidural hematomas. 15 cases and a review of
      the literature].
AB  - PURPOSE OF THE STUDY: In the literature, the frequency of postoperative
      compressive spinal epidural hematomas (SEH) appearing very low, we conducted the
      present study to determine the frequency of this complication in their unit and
      look for causative and predisposing factors. MATERIAL AND METHODS: Among the
      1,487 spinal operations performed in our unit between September 1997 and August
      1998, fifteen patients had postoperative compressive SEH; their files were
      retrospectively analyzed regarding the initial intervention, postoperative
      period, revision operation and neurologic follow-up. RESULTS: Five women and ten
      men were involved ranging in age from 47 to 70 years (average, 59.5 years). The
      primary intervention concerned the cervical spine in one case, the thoracic spine
      in seven and the lumbar spine in seven. Ten of the fifteen cases including all
      seven of the thoracic SEH (performed for compressive metastatic epiduritis)
      involved a laminectomy. A stenotic canal was the indication for the primary
      intervention in six of the seven lumbar cases. The average delay before onset of
      symptoms was 1.5 hours, 3.7 hours, and 5.3 hours after the cervical, thoracic,
      and lumbar interventions, respectively. The clinical pattern began with segmental
      pain rapidly followed first by bilateral radicular sensory deficit, then
      unilateral or bilateral motor deficit, except in the patients with thoracic SEH
      in whom segmental pain was followed by signs of cord impingement. Excluding the
      four cases in which diagnosis was retarded by work-up examinations (3 cases) or a
      misleading picture (1 case), revision surgery was performed from 1.25 to 4 hours
      after onset of symptoms (average, 2.75 hours). In the patients for whom
      reoperation was delayed, SEH resulted in permanent complete paralysis or
      sphincter dysfunction. In contrast, eight of the ten patients who were reoperated
      within four hours of the onset of symptoms either recovered completely or
      recovered their former neurologic status. DISCUSSION: Compressive SEH after
      spinal surgery is rare, only 41 cases having been reported aside from the series
      of Deburge et al. In the literature, the frequency is around 1 to 2 for 1000
      operations for some authors, as opposed to 3 p. 100 and 6 p. 100 found by two
      other groups. The 1 p. 100 of the present series is close to the latter values.
      Nonetheless, it is probably important to take the type of surgery into account,
      as shown by the current series in which SEH occurred after 5.9 p. 100 of the
      operations for metastasis, but only once out of 304 anterior cervical
      interventions. To reduce the risk as much as possible, it is important to be
      aware of the factors that may contribute to this complication. Several
      recommendations concerning prevention of SEH are thus discussed. Once SEH has
      occurred, the only modifiable prognostic factor appears to be the delay before
      reintervention. CONCLUSION: Although postoperative SEH is relatively rare, it may
      have dramatic consequences. In our opinion, reintervention must be performed as
      soon as possible after the onset of neurologic deficit, the work-up
      investigations only prolonging the critical surgical delay, which is probably the
      only alterable prognostic factor.

PMID- 10880934
TI  - [Fractures of the shaft of the humerus: systematic plate fixation. Anatomic and
      functional results in 156 cases and a review of the literature].
AB  - PURPOSE OF THE STUDY: Based on our experience with plate fixation of humeral
      shaft fractures and an analysis of the international literature, we attempted to
      answer the following questions. What functional outcome and what complications
      can be expected after surgery? Are the classical complications of open fracture
      surgery (screw fixation, wiring, plate fixation without compression.) as frequent
      after plate fixation using the Muller technique? MATERIAL AND METHODS: We
      reviewed our series of 156 humeral shaft fractures (61 p. 100 men, mean age 45
      years) including 21 cases of multiple trauma and 24 multiple fractures. A
      floating elbow was present in 8 cases and skin opening in 16. Initial radial
      deficiency was observed in 28 cases. Plate fixation was the only method used for
      the humeral shaft fractures. We used the modified Stewart and Hundley
      classification. RESULTS: Postoperative paralysis occurred in 8 cases (5.1 p. 100,
      5 complete paralysis); only one patient suffered persistent severe sequelae.
      There were also 8 malunions and 3 late consolidations. Consolidation rate was
      94.2 p. 100, sepsis rate was 1.5 p. 100. Good or very good outcome was achieved
      in 86.6 p. 100 of the cases. DISCUSSION: In the literature, (71 series, 5 000
      patients), plate fixation of humeral shaft fractures has given very good
      functional results with few initial failures, malunions or cases of sepsis.
      Radial paralysis is cited as a complication in 6.5 p. 100 of all plate fixations
      but is reversible in 90 p. 100 of cases. Classical orthopedic methods and
      centromedullar techniques produce more stiffness. The Sarmiento cuff can give
      good results after rigorous patient selection. CONCLUSION: Plate fixation
      according to the Muller technique is a reliable osteosynthesis method with few
      initial failures or malunions as evidenced by data in the literature. Infection
      is also rare. Although the radial nerve risk makes this technique rather
      difficult, excellent functional results can be achieved.

PMID- 10880935
TI  - [Implantation of iliosacral screws. Simulation of optimal placement by 3
      dimensional X-ray computed tomography].
AB  - PURPOSE OF THE STUDY: Percutaneous iliosacral screws are used advantageously to
      fix unstable pelvic girdle avoiding the morbidity of open access for conventional
      screw fixation. The insertion technique must be precise due to the risk of injury
      to the lumbosacral nerve trunk, the cauda equina roots, and the first sacral
      nerve. We undertook a study of the implantation site of iliosacral screws looking
      for a means of standardizing the drilling procedure on the basis of 3D computed
      tomography (CT) data. MATERIAL AND METHODS: A CT series with 3D reconstruction
      was performed on 11 pelvis bones. We retained pelvis parameters and characterized
      the axis and narrow zone of the sacral wing. The insertion routes of 6.5 mm
      cancelous bone screws were simulated: two iliosacral routes fixing S1, and two
      iliosacroiliac routes fixing S1 and S2. The values of the pelvic parameters and
      the positions of the screws were compared with the Spearman correlation test and
      graphic regression. RESULTS: The pelvic incidence was a mean 47 degrees. The
      length of the sacral wing was a mean 73 mm. The narrow zone of the wing was 47 mm
      from the lateral iliac fossa. In the narrow zone, the wing section showed an oval
      shape: 22 mm largest diameter, 11 mm smallest diameter. The wing was oriented 84
      degrees in the paracoronal plane perpendicular to the plane of the sacral plate,
      67 degrees in the para-axial plane parallel to the sacral plate, and 37 degrees
      in the sagittal plane of the subject. The length of the upper S1 screw was a mean
      80 mm. This upper screw was inclined 89 degrees in the para-coronal plant, 61
      degrees in the para-axial plane and 28 degrees in the sagittal plane. The length
      of the lower S1 screw as a mean 80 mm. This lower screw was inclined 74 degrees
      in the para-coronal plane, 91 degrees in the para-axial plane and 110 degrees in
      the sagittal plane. The fixation screws could be inserted in 12 out of 22 cases.
      Correlations were found with height of the subject, length of the wing and the
      screw, and screw inclination. The inclination of the upper S1 screw in the para
      coronal plane was correlated with the larger diameter of the sacral wing.
      DISCUSSION: The pelvis parameters measured were comparable with data in the
      literature. The very small dimensions of the narrow zone dictate a very precise
      drilling for the narrow zone. This narrow zone determines the inclination of the
      screw insertion. In the sagittal plane the standard deviation was very large
      making it impossible to interpret the data. The route of the upper screw runs
      obliquely forward in the plane parallel to the sacral plate. The lower screw runs
      upwardly in the plane perpendicular to the sacral plate. It does not appear
      possible to insert fixation screws in a routine procedure. Preoperative
      assessment would be necessary before percutaneous insertion. CONCLUSION: The 3D
      CT reconstructions of the sacral wing can be used to determine the precise
      optimal position of the two iliosacral screws. The principle orientations can be
      deducted from the plane of the sacral plate. Approximate indications can help
      reduce operative time and exposure to irradiation (patient and surgeon).
      Percutaneous iliosacroiliac screw fixation cannot be proposed for all patients.

PMID- 10880936
TI  - [Effectiveness of postoperative drainage after bipolar sealed endoprosthetic
      arthroplasty for femur neck fracture. Results of a prospective randomized study
      of 86 cases].

PMID- 10880937
TI  - [MacFarland fractures. A series of 24 cases].
AB  - PURPOSE OF THE STUDY: MacFarland fracture is a joint fracture of the ankle in
      children. The fracture line passes through the medial part of the lower
      epiphyseal disk of the tibia. Prognosis is dominated by later risk of
      malalignment and osteoarthritis. MacFarland fracture usually occurs subsequent to
      adduction trauma. The aim of this study was to analyze prognosis in a
      retrospective series of children with MacFarland fractures. MATERIAL AND METHOD:
      The series included 24 cases (14 boys and 10 girls, mean age at the time of
      trauma 12.7 years, age range 10-15 years). The fractures were classed into two
      groups according to the Salter and Harris classification for epiphyseal
      detachment: Salter 3 (n=4) and Salter 4 (n=20). Surgical treatment was given in
      17 cases (11 screw fixations, 4 pin fixations and 2 other ostheosynthesis
      combinations). Orthopedic care was given in 7 cases (mean immobilization=40
      days). All 24 children were followed for a mean 3 years 2 months (3 months=12
      years). Three outcome categories were used: good (no pain, stiffness or
      malalignment), fair (pain and/or stiffness, no malalignment), and poor
      (malalignment). RESULTS: Overall results were good in 15 cases, fair in 2 and
      poor in 7 (29 p. 100). Ankle malalignments (7 cases) required surgical
      correction: epiphysiodesis for varus<5, supramalleolar tibial valgization
      osteotomy for varus > 5 degrees. After these procedures, outcome was good with a
      normally aligned painless ankle at 13 months follow-up. Among factors predictive
      of malalignment (poor outcome), power of the initial trauma (traffic or sports
      accident in 5 of the 7 poor outcomes), crush injury (medial metaphyseal
      comminution in two cases which led to varus ankle despite well conducted
      treatment), fracture type (7 malalignments among the Salter 4 fractures versus
      none among the Salter 3 fractures), initially defective reduction or
      osteosynthesis material passing through the epiphyseal disk leading to
      epiphysiodesis. DISCUSSION: Careful radiologic and clinical surveillance is
      needed and should be continued to the end of growth (fusion of the tibial
      cartilage) in children with high risk fractures in order to detect epiphysiodesis
      early and avoid secondary malalignment. Surgical correction does remain possible
      and gives good results.

PMID- 10880938
TI  - [Comminuted fractures in multiple trauma patients: an analysis of 31 cases].
AB  - PURPOSE OF THE STUDY: We analyzed calcaneum burst fractures in multiple trauma
      patients and propose a management scheme. MATERIAL AND METHODS: In a
      retrospective study, we isolated 23 patients with 31 calcaneum burst fractures.
      All were stage V in the Duparc classification. We call them "pied de mine"
      fractures as they resembled those described in military reports. Half of them (16
      cases; 54%) were open fractures. All patients suffered multiple injuries and 12
      had a psychiatric history. These fractures were associated with spinal fracture
      in 17 cases (73%) and half had neurologic deficit, limb fracture in 16 (73%), and
      pelvic fracture in 12 (52%). The most frequent associated foot injuries were a
      talus fracture in 9 cases (29%) and Chopart displacement in 10 cases (32%).
      Clinical evaluation used the Maryland foot score, foot print and radiologic
      evaluation with lateral retrotibial view. RESULTS: Mean follow-up was 35 months.
      Mean Maryland foot score was 62.7 and 13 cases were pain free. Pain was due to
      conflict with the lateral malleolus, bony plantar thorns, medial malleolus and
      subtalar osteoarthritis. Orthopedic shoes were used 11 times. The other patients
      used sports shoes. Subtalar mobility was most frequently absent (23/29 cases, 2
      amputations). Foot print showed 13/16 flat feet; 6 thorns were indirectly
      visible. Two patients had retraction toes and were initially treated by external
      fixation. Radiologic evaluation showed 23/29 complete subtalar arthrodeses, 23/29
      migration of the great tuberosity, often(17/23 cases) associated with varus
      angulation. Eleven patients needed subsequent surgery: 5 for arthrodeses and 6
      for resection of bony thorns. Rate of complication was high, especially for open
      fractures: 2 infections for 15 closed fractures, and 8 infections (50%) for 16
      open fractures with 2 cases of chronic osteitis. Secondary amputation was
      required in 2/31 cases due to sepsis. TREATMENT PROPOSITIONS: For closed
      calcaneum burst fractures, it is better to wait one week before osteosynthesis.
      This delay is used to decrease edema with limb elevation and compressive
      bandaging. Skin tension due to trauma is increased by edema and osteosynthesis
      gives a high risk of wound disunion. We recommend reduction and Y-plate fixation
      even for burst fracture. Reduction must lower the tuberosity and correct the
      varus. After surgery, subtalar spontaneous arthrodesis is usually observed in a
      good position. Any bony plantar thorn must be resected. For open calcaneum burst
      fracture, the risk of sepsis is high. First treatment is debridement,
      stabilization and external fixation with antibiotic therapy. Stabilization should
      improve vascularization and facilitate internal fixation. The external fixation
      can be placed on the medial side to free the lateral approach to the calcaneum.
      Flap repair can be performed after one week when skin tension has subsided and
      areas of necrosis controlled.

PMID- 10880939
TI  - [Sagittal equilibrium of the pelvis: analysis of the inclination of the ischio
      pubic ramus from the horizontal].
AB  - PURPOSE OF THE STUDY: The sagittal equilibrium of the spine and pelvis has been
      examined in numerous studies looking for the origin of certain posture disorders
      of the spine and the cause of lower back pain. Sagittal x-rays of the pelvis
      provide an analysis of the degree of inclination of the pelvis from the
      horizontal and the bi-coxo-femoral axis and information on the form of the
      sacrum. There is no radiographic parameter however which analyzes the transition
      between the pelvis-sacrum component and the femoral component, i.e. the
      periacetabular region. In the sagittal plane, a line tangent to the ischio-pubic
      ramus would appear to best reflect the orientation of the periacetabular region
      and the muscular forces applied to this region. The purpose of this work was to
      analyze the inclination of the ischio-pubic ramus from the horizontal and its
      relations with other sagittal radiographic parameters in a population of growing
      children with spinal disorders. MATERIALS AND METHOD: The study population
      included 100 children with spinal disorders who underwent a teleradiographic
      series with lateral view in the upright position. Most of the children had
      scoliosis (80 cases), 7 had kyphoscoliosis, 4 isthmic spondylolysis with
      spondylolisthesis, 1 spondylodiscitis and 4 lower back pain. Mean age was 13
      years (range 2.5-22 years). We measured 7 radiographic parameters: lumbo-sacral
      angle, slope of the sacrum, pelvic version, incidence, thickness, overhang, and
      inclination of the ischio-pubic ramus from the horizontal. Data were analyzed to
      search for correlations between radiographic parameters and between radiographic
      parameters and clinical features. RESULTS: Mean inclination of the ischio-pubic
      ramus from the horizontal was 33.9 degrees (SD =5.9 degrees ). The only positive
      statistical correlation between the inclination of the ischio-pubic ramus and the
      clinical data was a relationship with the position of the arms compared with the
      horizontal (p =0.04). There was no correlation with age, sex, ethnic background,
      etiology. There was no correlation between the inclination of the ischio-pubic
      ramus and the other radiographic parameters (coefficient r ranging from 0.06 to
      0.43). DISCUSSION: The interdependence of sagittal radiographic parameters of the
      pelvis and the spine have been largely demonstrated. Certain pathological
      situations (isthmic spondylolysis with spondylolisthesis, lower back pain, etc.)
      can be explained by the value of these parameters, particularly incidence. The
      inclination of the ischio-pubic ramus from the horizontal reflects the
      periacetabular region. When analyzed in the sagittal plane, it was found to be a
      more stable parameter, independent of most clinical criteria (particularly age,
      and etiology) and of the other radiographic parameters studied. The only
      determining factor appears to be acquisition of the upright position. The
      consistency of this parameter constrasts with the variability of the other
      radiographic parameters of the pelvis and the spine, particularly incidence,
      although the inclination of the ischio-pubis ramus is an expression of a region
      different than the pelvis. This study suggests that the periacetabular region
      plays a key role in acquisition of the upright position in humans. The
      periacetabular region would be a fixed point around which the lower limbs and
      spine describe varying orientations.

PMID- 10880940
TI  - [Retrosternal dislocation of the clavicle complicated by subclavian venous
      thrombosis. Case report and review of the literature].
AB  - Retrosternal dislocation of the clavicle is a highly uncommon lesion. Diagnosis
      may be delayed with the risk of discovery after severe complications resulting
      from the protrusion of the medial part of the clavicle into the anterosuperior
      mediastinum. Currently, diagnosis is based on computed tomographic findings. We
      report a case of retrosternal dislocation of the clavicle complicated by
      subclavian venous thrombosis and review the therapeutic indications proposed in
      the literature.

PMID- 10880941
TI  - [Transverse fracture of the upper sacrum with major displacement. CT
      reconstruction: case report].
AB  - PURPOSE OF THE STUDY: Transverse fractures of the upper sacrum are rare. We
      report a case with major displacement and neurological impairment. The use of 3D
      computed tomography (CT) reconstruction to facilitate preoperative planning and
      surgical procedure is discussed. MATERIALS AND METHODS: A 49-year-old depressive
      woman jumped from the second floor in an attemp to commit suicide. She presented
      an absence of motor reponse in L5 region on both sides, hypoesthesia of S1
      dermatome, perineal problems including saddle hypoesthesia and a hypotonic anal
      sphincter. Radiologic investigation showed a transverse fracture of the upper
      sacrum with major displacement. CT with 3D reconstruction visualized the course
      of the different fracture lines on the different levels of the sacrum. Open
      reduction, extensive laminectomy and internal fixation were performed 6 days
      following the injury. RESULTS: After a 1-year post-operative follow up, complete
      neurological recovery with normal walking and full perineal sphincter control was
      observed. DISCUSSION AND CONCLUSION: Fractures of the upper sacrum with major
      displacement are exceptional. They require well prepared surgical management. CT
      series with 3D reconstruction allow an analysis of the course of the different
      sagittal fracture lines to facilitate surgical planning.

PMID- 10880942
TI  - [Acute compartment syndrome in the thigh: 3 cases].
AB  - We report three cases of compartment syndrome in the thigh related to drug
      intoxications. Compartment syndrome is an uncommon condition often diagnosed late
      as it may occur in unconscious patients. The typical clinical presentation begins
      with pain of the lower limb refractory to major antagesics. The condition then
      progresses with sensoromotor involvement of the sciatic nerve. Rapid onset of
      acute renal failure in the setting of a crush syndrome may be life-threatening
      with a long-term risk of major sensoromotor sequelae. Surgical treatment with
      aponeurotomy is required rapidly to limit sequelae.

PMID- 10880943
TI  - [Preoperative chemotherapy for non-small-cell lung cancer].

PMID- 10880944
TI  - [Nicotine dependence].
AB  - Nicotine is the principle alkaloid in tobacco and is considered to be responsible
      for tobacco dependence due to its psychoactive properties and its capacity to
      induce self-administration behavior in animals. Its action affects the brain
      where it binds to specific nicotinic receptors distributed on the mesolimbic and
      mesocortial dopaminergic pathways. Dopamine release by the nerve endings on these
      pathways provokes activation of the cerebral response. Acute stimulation with
      nicotine provokes a rise in cerebral dopamine levels in the accumbens. Dopamine
      release is greatly lowered in animals having undergone chronic exposure to
      nicotine, suggesting desensitization of the nicotinic receptors. In the regular
      smoker, there is an increase in the number of cerebral nicotinic receptors which
      would be a neuroadaptation response to desensitization. Reduction in the serum
      nicotine level favors resensitization of the nicotinic receptors and their
      vacuity would be the cause of the withdrawal syndrome. In therapeutics, nicotinic
      substitutes can effectively suppress the withdrawal syndrome and lead to
      abstinence rates to the order of 20 to 25% at one year. Psychotropes can also be
      effective to help patients stop smoking. Their mechanism of action is not clearly
      established but most would act by increasing the level of cerebral dopamine. They
      are used independently of their antidepressor effect with abstinence rates to the
      order of 25 to 30% at one year. Their combination with nicotinic substitutes can
      increase the rate of success.

PMID- 10880945
TI  - [New administration modalities for radiotherapy in lung cancer].
AB  - Much progress has been made in recent years in administration modalities for
      radiotherapy for lung cancer. Exposure time to external irradiation was the first
      parameter to be modified: hyperfractionated radiotherapy, hyperfractionated
      accelerated radiotherapy with or without concomitant irradiation, synchronous or
      asynchronous protocols, split course radiotherapy. Radiosensitizing agents have
      also been the subject of much research: radiosensitization of hypoxic cells,
      modifiers of the biological response, concomitant radiochemotherapy. The main
      drugs used are 5-fluorouracil, platinum salts, etoposide, hydroxyurea, taxanes,
      topotecan, vinorelbin, and gemcitabine. Outcome with these combinations is
      discussed, both for non-small-cell and small-cell lung cancer. 3D conformational
      radiotherapy can enable increased dosing in the tumoral target while better
      preserving healthy tissues. High dose endoluminal brachytherapy is used
      particularly as a palliative treatment for bronchial obstructions or as curative
      treatment for weakly infiltrative small endoluminal tumors.

PMID- 10880947
TI  - [Thoracoscopic treatment of pulmonary hydatidosis: a case report].
AB  - Hydatidosis is a ubiquitous parasitic condition observed in a pulmonary
      localization in 30 to 40% of cases. The hydatid cyst develops slowly and is well
      tolerated by the host who presents no signs for a long period. Complications
      include compression, fissuration, rupture, anaphylactic shock or infection after
      a latency phase of variable duration. Treatment of pulmonary hydatidosis is
      classically surgical with enucleation of the cyst by cleavage between the
      adventice and the anhistic membrane via thorachotomy using the Ugon and Barret
      procedure. Needle aspiration is also possible via thorachotomy or thoracoscopy.
      Finally resection of the pulmonary parenchyma can be used to excise the hydatic
      cyst. We describe a thoracoscopic treatment using specific material, in a man
      with complications due to a voluminous pulmonary hydatid cyst.

PMID- 10880946
TI  - [Phase II trial with cystemustine (60 mg/m2) in advanced or metastatic pretreated
      lung carcinoma].
AB  - From January 1990 to November 1994, 23 patients with advanced pretreated lung
      carcinoma were enrolled into a phase II trial to test a new nitrosourea,
      cystemustine, given every 2 weeks at the dose of 60 mg/m(2) in a 15-minute IV
      infusion. All eligible patients were considered evaluable for response and
      toxicity (WHO criteria).

PMID- 10880948
TI  - [Dermatomyositis and small-cell lung cancer : fortuitous association or
      paraneoplastic syndrome?].
AB  - Dermatomyositis, an inflammatory muscle disease probably related to dysimmunity,
      is associated with character skin eruptions. Dermatomyositis is often associated
      with cancer (15 to 40% of cases depending on the series). All histological types
      and all cancer localizations observed in the general population can be associated
      with dermatomyositis. We report the case of a patient with dermatomyositis who
      developed small-cell lung cancer. There have been few descriptions of this
      association in the literature. Certain clinical features of dermatomyositis would
      be predictive of its paraneoplastic nature. Prognosis is very poor. Treatment is
      basically dictated by the underlying neoplasia.

PMID- 10880949
TI  - [Solitary cerebellous tumor discovered at extension work-up for primary lung
      cancer].

PMID- 10880950
TI  - [Mounier-Kuhn syndrome: pulmonary tuberculosis sequela in a diabetic patient].

PMID- 10880952
TI  - [Did you read this issue? [In Process Citation]

PMID- 10880951
TI  - [Prevalence of tuberculosis in sickle cell Africans].
AB  - We performed a cross-sectional analysis of 68 files of patients with a major form
      of drepanocytosis and hospitalized for lower respiratory tract infection over a 6
      year period. The frequency of respiratory infections was 32.69%. Non-tuberculosis
      infections dominated (64,68, 94%). Tuberculous infection was less frequent and
      occurred in 4/68 (6%). Extensive disease was frequent and diagnosis difficult.

PMID- 10880953
TI  - Families of retinoid dehydrogenases regulating vitamin A function: production of
      visual pigment and retinoic acid.
AB  - Vitamin A (retinol) and provitamin A (beta-carotene) are metabolized to specific
      retinoid derivatives which function in either vision or growth and development.
      The metabolite 11-cis-retinal functions in light absorption for vision in
      chordate and nonchordate animals, whereas all-trans-retinoic acid and 9-cis
      retinoic acid function as ligands for nuclear retinoic acid receptors that
      regulate gene expression only in chordate animals. Investigation of retinoid
      metabolic pathways has resulted in the identification of numerous retinoid
      dehydrogenases that potentially contribute to metabolism of various retinoid
      isomers to produce active forms. These enzymes fall into three major families.
      Dehydrogenases catalyzing the reversible oxidation/reduction of retinol and
      retinal are members of either the alcohol dehydrogenase (ADH) or short-chain
      dehydrogenase/reductase (SDR) enzyme families, whereas dehydrogenases catalyzing
      the oxidation of retinal to retinoic acid are members of the aldehyde
      dehydrogenase (ALDH) family. Compilation of the known retinoid dehydrogenases
      indicates the existence of 17 nonorthologous forms: five ADHs, eight SDRs, and
      four ALDHs, eight of which are conserved in both mouse and human. Genetic studies
      indicate in vivo roles for two ADHs (ADH1 and ADH4), one SDR (RDH5), and two
      ALDHs (ALDH1 and RALDH2) all of which are conserved between humans and rodents.
      For several SDRs (RoDH1, RoDH4, CRAD1, and CRAD2) androgens rather than retinoids
      are the predominant substrates suggesting a function in androgen metabolism as
      well as retinoid metabolism.

PMID- 10880954
TI  - Ceramide mimics tumour necrosis factor-alpha in the induction of cell cycle
      arrest in endothelial cells. Induction of the tumour suppressor p53 with decrease
      in retinoblastoma/protein levels.
AB  - Tumour necrosis factor (TNF)-alpha induces a transient increase in N
      octanoylsphingosine (C8-ceramide) which has been postulated as an intracellular
      mediator in TNF-alpha signalling. We tested the ability of C8-ceramide to
      reproduce the TNF-alpha-mediated interference with endothelial cell proliferation
      and DNA synthesis. TNF-alpha (10 ng.mL-1) and C8-ceramide (20 microM) inhibited
      the incorporation of [3H]thymidine into DNA and led to an accumulation of cells
      in the G1 phase of the cell cycle. When the responses of the tumour suppressors
      p53 and RB were analysed, it was found that TNF-alpha and C8-ceramide induced
      increased expression of p53. Treatment with TNF-alpha or C8-ceramide lead to a
      significant decrease in total retinoblastoma protein (RB) content that correlated
      with high levels of p53. These results suggest that p53 and RB may complement
      each other in their contribution to cell cycle arrest. TNF-alpha prevented RB
      phosphorylation whereas C8-ceramide did not interfere with this process,
      suggesting that it follows a ceramide-independent pathway.

PMID- 10880955
TI  - Flexibility of myosin-subfragment-1 in its complex with actin as revealed by
      fluorescence resonance energy transfer.
AB  - The flexibility of the acto-myosin complex in rigor conditions was characterized
      by measuring the temperature profile of normalized fluorescence resonance energy
      transfer efficiency, f' [Somogyi, B., Matko, J., Papp, S., Hevessy, J., Welch,
      G.R. & Damjanovich, S. (1984) Biochemistry 23, 3403-3411]. Fluorescence acceptors
      were introduced to the Cys374 residues of actin and the donors were covalently
      attached either to Cys707 in the catalytic domain or to Cys177 in the essential
      light-chain of myosin S1. Fluorescence resonance energy transfer measurements
      revealed that the protein matrix between Cys374 of actin and Cys707 of S1 is
      rigid. In contrast, the link between the catalytic and light-chain-binding
      domains in myosin S1 is flexible. We have recently shown that the positional
      distribution of Cys707 was narrow relative to the actin filament, while that of
      the Cys177 was broad. Accordingly, the broad positional distribution of Cys177 is
      likely to be due to the large flexibility of the link between the catalytic and
      light-chain-binding domains. This flexibility is probably essential for the
      interdomain reorganization of the myosin head during the force generation process
      and for accommodating the symmetry difference between actin and myosin filaments
      to allow the formation of cross-bridges.

PMID- 10880956
TI  - Gelsolin as a calcium-regulated actin filament-capping protein.
AB  - Various concentrations of gelsolin (25-100 nM) were added to 2 microM polymerized
      actin. The concentrations of free calcium were adjusted to 0.05-1.5 microM by
      EGTA/Ca2+ buffer. Following addition of gelsolin actin depolymerization was
      observed that was caused by dissociation of actin subunits from the pointed ends
      of treadmilling actin filaments and inhibition by gelsolin of polymerization at
      barbed ends. The time course of depolymerization revealed an initial lag phase
      that was followed by slow decrease of the concentration of polymeric actin to
      reach the final steady state polymer and monomer concentration. The initial lag
      phase was pronounced at low free calcium and low gelsolin concentrations. On the
      basis of quantitative analysis the kinetics of depolymerization could be
      interpreted as capping, i.e. binding of gelsolin to the barbed ends of actin
      filaments and subsequent inhibition of polymerization, rather than severing. The
      main argument for this conclusion was that even gelsolin concentrations (100 nM)
      that exceed the concentration of filament ends ( approximately 2 nM), cause the
      filaments to depolymerize at a rate that is similar to the rate of
      depolymerization of the concentration of pointed ends existing before addition of
      gelsolin. The rate of capping is directly proportional to the free calcium
      concentration. These experiments demonstrate that at micromolar and submicromolar
      free calcium concentrations gelsolin acts as a calcium-regulated capping protein
      but not as an actin filament severing protein, and that the calcium binding sites
      of gelsolin which regulate the various functions of gelsolin (capping, severing
      and monomer binding), differ in their calcium affinity.

PMID- 10880957
TI  - A protein factor of rat liver mitochondrial matrix involved in flavinylation of
      dimethylglycine dehydrogenase.
AB  - The involvement of rat liver mitochondria in the flavinylation of the
      mitochondrial matrix flavoenzyme dimethylglycine dehydrogenase (Me2GlyDH) has
      been investigated. Me2GlyDH was synthesized as an apoenzyme in the rabbit
      reticulocyte lysate (RL) transcription/translation system and its flavinylation
      was monitored by virtue of the trypsin resistance of the holoenzyme. The rate of
      holoenzyme formation in the presence of FAD was stimulated with increasing
      efficiency by the addition of solubilized mitoplasts, mitochondrial matrix and
      DEAE-purified matrix fraction. Apo-Me2GlyDH was also converted into holoenzyme
      when the solubilized mitoplasts were supplemented with FMN and ATP. This
      observation is consistent with the existence of a mitochondrial FAD synthetase
      generating the FAD needed for holoenzyme formation from its precursors.
      Holoenzyme formation in the presence of FAD increased linearly with the
      concentration of matrix protein in the assay, and depended on the amount of
      externally added Me2GlyDH with saturation characteristics. These findings suggest
      the presence of a protein factor in the mitochondrial matrix which stimulates
      Me2GlyDH flavinylation. This factor was different from both mitochondrial heat
      shock protein (Hsp)70, as shown by immunodepletion experiments, and mitochondrial
      Hsp60, as demonstrated by the capability of a DEAE-purified matrix fraction
      devoid of Hsp60 to accelerate flavinylation of both RL translated and purified
      Me2GlyDH.

PMID- 10880958
TI  - Cloning, characterization and expression of complete coding sequences of three
      IgE binding Malassezia furfur allergens, Mal f 7, Mal f 8 and Mal f 9.
AB  - Malassezia furfur, formerly known as Pityrosporum orbiculare or P. ovale, is a
      yeast that colonizes human skin. Normally, this yeast is nonpathogenic but under
      the influence of predisposing factors it may induce IgE reactivity in patients
      with atopic dermatitis. Approximately 40-65% of atopic dermatitis patients have
      IgE antibodies and/or skin reactivity against M. furfur and a higher T-cell
      response against this yeast is found in atopic dermatitis patients than in
      healthy individuals. By making a cDNA library displayed on a phage surface, we
      previously cloned five different IgE-binding proteins, Mal f 5, Mal f 6, MF 7, MF
      8 and MF 9, from this yeast. The cDNAs encoding these allergens were sequenced
      and expressed in Escherichia coli. The sequences of MF 7, MF 8 and MF 9 were not
      full length (missing their 5'-ends) giving only partial gene products. To obtain
      complete cDNA sequences, we performed RACE-PCR to amplify the 5'-ends of each
      cDNA. These PCR products were sequenced and analyzed. The coding sequences of Mal
      f 7, Mal f 8 and Mal f 9 encode proteins with ORFs of 141 (16.2 kDa), 179 (19.2
      kDa) and 126 (14.0 kDa) amino-acid residues, respectively. None of the putative
      proteins showed significant sequence homology with other known proteins in the
      searched database. The proteins encoded by the complete cDNA sequences were
      expressed in E. coli as recombinant proteins. Immunoblotting and
      radioallergosorbant test data showed that all of the expressed recombinant
      proteins have the ability to bind serum IgE from atopic dermatitis patients and
      furthermore, the M. furfur extract could specifically inhibit this IgE binding.

PMID- 10880959
TI  - Identification of a nuclear export signal in MKK6, an activator of the carp p38
      mitogen-activated protein kinases.
AB  - Carp homologues of p38 mitogen-activated protein kinase (MAPK) and its activator
      MAPK kinase 6 (MAPKK6, referred to as MKK6) were identified. There exist at least
      two distinct carp p38s, cp38a and cp38b, both of which consist of 361 amino
      acids. The transcript of c38a was exclusively expressed in the ovary, whereas
      that of cp38b was ubiquitously expressed. Western blot analysis with anti
      (phosphorylated MAPK) Ig specific to the active p38 or JNK has shown that p38 was
      activated in response to hypertonic stress (1 M sorbitol) in epithelioma
      papilosum cyprini carp epithelial cells (EPC) and that the activation of p38
      proceeded faster to the maximal level than that of JNK. Carp homologue (cMKK6) of
      p38 activator MKK6 consists of 404 amino acids. It was expressed ubiquitously but
      was most abundant in the ovary. An in vitro kinase assay demonstrated that cMKK6
      is an upstream activator of cp38 and cp38b in carp because it specifically
      phosphorylated and activated cp38a and cp38b. Interestingly, we found that cMKK6
      has a nuclear export signal (NES) sequence in its N-terminal region although
      upstream activators of stress-activated MAPKs, p38 and JNK, do not in other
      animals. The NES sequence facilitated nuclear export of cMKK6 and ovalbumin.
      Leucine residues in the sequence were crucial for the NES activity, as the
      activity was lost on replacement of the leucines to alanines. The existence of an
      NES in cMKK6 implies the requisite of strict regulation of the p38 MAPK pathway
      in carp. The abundance of these components for the stress-activated pathway in
      the ovary might be related to ectogenetic early development.

PMID- 10880960
TI  - Homo-oligomer formation by basigin, an immunoglobulin superfamily member, via its
      N-terminal immunoglobulin domain.
AB  - Basigin (Bsg) is a highly glycosylated transmembrane protein with two
      immunoglobulin (Ig)-like domains. A number of studies, including gene targeting,
      have demonstrated that Bsg plays pivotal roles in spermatogenesis, implantation,
      neural network formation and tumor progression. In the present study, to
      understand the mechanism of action of Bsg, we determined its expression status on
      the plasma membrane. Cotransfection of Bsg expression vectors with two different
      tags clarified that Bsg forms homo-oligomers in a cis-dependent manner on the
      plasma membrane. If the disulfide bond of the more N-terminally located Ig-like
      domain was destroyed by mutations, Bsg could not form oligomers. In contrast, the
      mutations of the C-terminal Ig-like domain or N-glycosylation sites did not
      affect the association. The association of mouse and human Bsgs, which exhibit
      high homology in the transmembrane and intracellular domains but low homology in
      the extracellular domain, was very weak as compared with that within the same
      species, suggesting the importance of the extracellular domain in the
      association. If the extracellular domain of the human Ret protein was replaced
      with the N-terminal Ig-like domain of Bsg, the resulting chimera protein was
      associated with intact wild-type Bsg, but not if the C-terminal Ig-like domain,
      instead of the N-terminal one, of Bsg was used. No oligomer formation took place
      between the intact wild-type Ret and Bsg proteins. In conclusion, these data
      indicate that the N-terminal Ig-like domain is necessary and sufficient for
      oligomer formation by Bsg on the plasma membrane.

PMID- 10880961
TI  - Physical characterization of plakophilin 1 reconstituted with and without zinc.
AB  - Plakophilin 1 (PKP1) belongs to the arm-repeat protein family which is
      characterized by the presence of a conserved 42-amino-acid motif. Despite
      individual members of the family containing a similar type of structural domain,
      they exhibit diverse cellular functions. PKP1 is ubiquitously expressed in human
      tissues and, depending on the type of cell, found prominently in the karyoplasm
      and/or in desmosomes. In surface plasmon resonance detection experiments, we
      noticed that PKP1 specifically bound zinc but not calcium or magnesium. Therefore
      we have used circular dichroism spectroscopy, limited proteolysis, analytical
      ultracentrifugation, electron microscopy and dynamic light scattering to
      establish the physical properties of recombinant PKP1 depending on the presence
      or absence of zinc. The alpha helix content of PKP1 was considerably higher when
      reconstituted with zinc than without. By atomic absorption spectroscopy 7.3 atoms
      zinc were shown to be tightly associated with one molecule of wild-type PKP1. The
      zinc-reconstituted protein formed globular particles of 21.9 +/- 8.4 nm diameter,
      as measured by electron microscopy after glycerol spraying/rotary metal
      shadowing. In parallel, the average sedimentation coefficient (s20, w) for zinc
      containing PKP1 was 41S and its diffusion coefficient, as obtained by dynamic
      light scattering, 1.48 x 10-7 cm2.s-1. The molecular mass of 2.44 x 106 obtained
      from s and D yields an average stoichiometry of 30 for the PKP1 oligomer. In
      contrast, PKP1, reconstituted without zinc, contained no significant amount of
      zinc, sedimented with 4.6S, and was present in monomeric form as determined by
      sedimentation equilibrium centrifugation.

PMID- 10880962
TI  - Expression patterns of the regulatory proteins G protein-coupled receptor kinase
      2 and beta-arrestin 1 during rat postnatal brain development: effect of
      hypothyroidism.
AB  - G protein-coupled receptor kinase 2 (GRK2) and beta-arrestin 1 are key regulatory
      proteins that modulate the desensitization and resensitization of a wide variety
      of G protein-coupled receptors (GPCRs) involved in brain functions. In this
      report, we describe the postnatal developmental profile of the mRNA and protein
      levels of GRK2 and beta-arrestin 1 in rat brain. The expression levels of GRK2
      and beta-arrestin 1 display a marked increase at the second and third week after
      birth, respectively, consistent with an involvement of these proteins in brain
      maturation processes. However, the expression attained at birth and during the
      first postnatal week with respect to adult values (45-70% for GRK2, approximately
      30% for beta-arrestin 1) is relatively high compared to that reported for several
      GPCRs, indicating the existence of changes in the ratio of receptors to their
      regulatory proteins during brain development. On the other hand, we report that
      experimental hypothyroidism results in changes in the patterns of expression of
      GRK2 and beta-arrestin 1 in cerebral cortex, leading to a 25-30% reduction in
      GRK2 levels at several stages of development. Such changes could help to explain
      the alterations in GPCR signaling that occur during this pathophysiological
      condition.

PMID- 10880963
TI  - Increased methyl esterification of altered aspartyl residues in erythrocyte
      membrane proteins in response to oxidative stress.
AB  - Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT; EC 2. 1.1.77)
      catalyses the methyl esterification of the free alpha-carboxyl group of abnormal
      L-isoaspartyl residues, which occur spontaneously in protein and peptide
      substrates as a consequence of molecular ageing. The biological function of this
      transmethylation reaction is related to the repair or degradation of age-damaged
      proteins. Methyl ester formation in erythrocyte membrane proteins has also been
      used as a marker reaction to tag these abnormal residues and to monitor their
      increase associated with erythrocyte ageing diseases, such as hereditary
      spherocytosis, or cell stress (thermal or osmotic) conditions. The study shows
      that levels of L-isoaspartyl residues rise in membrane proteins of human
      erythrocytes exposed to oxidative stress, induced by t-butyl hydroperoxide or
      H2O2. The increase in malondialdehyde content confirmed that the cell membrane is
      a primary target of oxidative alterations. A parallel rise in the methaemoglobin
      content indicates that proteins are heavily affected by the molecular alterations
      induced by oxidative treatments in erythrocytes. Antioxidants largely prevented
      the increase in membrane protein methylation, underscoring the specificity of the
      effect. Conversely, we found that PCMT activity, consistent with its repair
      function, remained remarkably stable under oxidative conditions, while damaged
      membrane protein substrates increased significantly. The latter include ankyrin,
      band 4.1 and 4.2, and the integral membrane protein band 3 (the anion exchanger).
      The main target was found to be particularly protein 4.1, a crucial element in
      the maintenance of membrane-cytoskeleton network stability. We conclude that the
      increased formation/exposure of L-isoaspartyl residues is one of the major
      structural alterations occurring in erythrocyte membrane proteins as a result of
      an oxidative stress event. In the light of these and previous findings, the
      occurrence of isoaspartyl sites in membrane proteins as a key event in
      erythrocyte spleen conditioning and hemocatheresis is proposed.

PMID- 10880964
TI  - Identification and characterization of alternative splice products encoded by the
      human phosphotyrosyl phosphatase activator gene.
AB  - The phosphotyrosyl phosphatase activator (PTPA), a protein phosphatase 2A (PP2A)
      regulatory protein, specifically stimulates the phosphotyrosyl phosphatase
      activity of PP2A in vitro. Human PTPA is encoded by a single gene, the structure
      and chromosomal localization of which have been determined in our previous work.
      In this paper, we report the identification and characterization of six
      additional splice variants, termed PTPAbeta to PTPAeta, in addition to the
      originally identified PTPAalpha form. Interestingly, PTPAbeta and PTPAgamma
      contain a novel exon that had been overlooked in the formerly identified gene
      structure. As revealed by nested PCR, all these PTPA transcripts are expressed in
      various human cDNA libraries and cell lines. However, a quantitative approach,
      using a single PCR reaction followed by detection of the reaction products with a
      radioactively labeled probe, revealed only PTPAalpha, beta and delta, suggesting
      that the other transcripts are expressed very poorly. In vitro transcription
      translation revealed that only PTPAalpha, beta, delta and epsilon are translated
      into functional proteins, whereas translation of PTPAgamma, zeta and eta is
      stopped prematurely due to a frameshift resulting from skipping exon 2,
      suggesting that the latter isoforms may result from splicing errors. By western
      analysis of HepG2 and Saos-2 cell extracts, only PTPAalpha and beta were
      detected. PTPAalpha and beta were expressed as GST fusion proteins in bacteria,
      and were found to contain the same specific phosphotyrosyl phosphatase
      stimulatory activity towards PP2A. The identification of this family of PTPA
      variants adds another level of complexity to the in vivo function(s) of PTPA,
      opening up the possibility that different isoforms may perform different
      functions.

PMID- 10880965
TI  - Substrates enhance autophosphorylation and activation of p21-activated protein
      kinase gamma-PAK in the absence of activation loop phosphorylation.
AB  - The p21-activated protein kinase gamma-PAK from rabbit, expressed in insect
      cells, is activated following binding of Cdc42(GTPgammaS). The rate of
      autophosphorylation is increased fivefold and the protein kinase activity 13
      fold, as measured with the synthetic heptapeptide (AKRESAA). The mutant K278R,
      where the invariant lysine in the catalytic site is replaced by arginine, shows
      neither autophosphorylation nor activity. Replacement of the conserved threonine
      in the catalytic domain with alanine (T402A) reduces autophosphorylation and
      protein kinase activity to 1% that of the wild-type gamma-PAK, indicating
      autophosphorylation of Thr402 in the activation loop is essential for protein
      kinase activity. In contrast, certain protein substrates such as histone 2B,
      histone 4 and myelin basic protein, stimulate both autophosphorylation and
      protein kinase activity to levels similar to those observed with
      Cdc42(GTPgammaS). This substrate-level activation does not require
      autophosphorylation of Thr402 in the activation loop. As shown with T402A, the
      protein kinase activity with histone 4 is similar to that observed with
      recombinant wild-type gamma-PAK. Basic proteins or peptides which are not
      substrates of gamma-PAK, such as histone 1 and polylysine, do not stimulate
      autophosphorylation or activity. Other substrates such as the Rous sarcoma virus
      protein NC are phosphorylated by gamma-PAK following activation by
      Cdc42(GTPgammaS), but are not phosphorylated by T402A. The data suggest that some
      substrates can override the requirement for Cdc42(GTPgammaS), by activating gamma
      PAK directly.

PMID- 10880966
TI  - Murine FATP alleviates growth and biochemical deficiencies of yeast fat1Delta
      strains.
AB  - Saccharomyces cerevisiae is an ideal model eukaryote for studying fatty-acid
      transport. Yeast are auxotrophic for unsaturated fatty acids when grown under
      hypoxic conditions or when the fatty-acid synthase inhibitor cerulenin is
      included in the growth media. The FAT1 gene encodes a protein, Fat1p, which is
      required for maximal levels of fatty-acid import and has an acyl CoA synthetase
      activity specific for very-long-chain fatty acids suggesting this protein plays a
      pivotal role in fatty-acid trafficking. In the present work, we present evidence
      that Fat1p and the murine fatty-acid transport protein (FATP) are functional
      homologues. FAT1 is essential for growth under hypoxic conditions and when
      cerulenin was included in the culture media in the presence or absence of
      unsaturated fatty acids. FAT1 disruptants (fat1Delta) fail to accumulate the
      fluorescent long-chain fatty acid fatty-acid analogue 4, 4-difluoro-5-methyl-4
      bora-3a,4a-diaza-s-indacene-3-do decanoic acid (C1-BODIPY-C12), have a greatly
      diminished capacity to transport exogenous long-chain fatty acids, and have very
      long-chain acyl CoA synthetase activities that were 40% wild-type. The depression
      in very long-chain acyl CoA synthetase activities were not apparent in cells
      grown in the presence of oleate. Additionally, beta-oxidation of exogenous long
      chain fatty acids is depressed to 30% wild-type levels. The reduction of beta
      oxidation was correlated with a depression of intracellular oleoyl CoA levels in
      the fat1Delta strain following incubation of the cells with exogenous oleate.
      Expression of either Fat1p or murine FATP from a plasmid in a fat1Delta strain
      restored these phenotypic and biochemical deficiencies. Fat1p and FATP restored
      growth of fat1Delta cells in the presence of cerulenin and under hypoxic
      conditions. Furthermore, fatty-acid transport was restored and was found to be
      chain length specific: octanoate, a medium-chain fatty acid was transported in a
      Fat1p- and FATP-independent manner while the long-chain fatty acids myristate,
      palmitate, and oleate required either Fat1p or FATP for maximal levels of
      transport. Lignoceryl CoA synthetase activities were restored to wild-type levels
      in fat1Delta strains expressing either Fat1p or FATP. Fat1p or FATP also restored
      wild-type levels of beta-oxidation of exogenous long-chain fatty acids. These
      data show that Fat1p and FATP are functionally equivalent when expressed in yeast
      and play a central role in fatty-acid trafficking.

PMID- 10880967
TI  - Cloning, sequencing and expression of the gene for flavodoxin from Megasphaera
      elsdenii and the effects of removing the protein negative charge that is closest
      to N(1) of the bound FMN.
AB  - The gene for the electron-transfer protein flavodoxin has been cloned from
      Megasphaera elsdenii using the polymerase chain reaction. The recombinant gene
      was sequenced, expressed in an Escherichia coli expression system, and the
      recombinant protein purified and characterized. With the exception of an
      additional methionine residue at the N-terminus, the physico-chemical properties
      of the protein, including its optical spectrum and oxidation-reduction
      properties, are very similar to those of native flavodoxin. A site-directed
      mutant, E60Q, was made to investigate the effects of removing the negatively
      charged group that is nearest to N(1) of the bound FMN. The absorbance maximum in
      the visible region of the bound flavin moves from 446 to 453 nm. The midpoint
      oxidation-reduction potential at pH 7 for reduction of oxidized flavodoxin to the
      semiquinone E2 becomes more negative, decreasing from -114 to -242 mV; E1, the
      potential for reduction of semiquinone to the hydroquinone, becomes less
      negative, increasing from -373 mV to -271 mV. A redox-linked pKa associated with
      the hydroquinone is decreased from 5.8 to < or = 4.3. The spectra of the
      hydroquinones of wild-type and mutant proteins depend on pH (apparent pKa values
      of 5.8 and < or = 5.2, respectively). The complexes of apoprotein and all three
      redox forms of FMN are much weaker for the mutant, with the greatest effect
      occurring when the flavin is in the semiquinone form. These results suggest that
      glutamate 60 plays a major role in control of the redox properties of M. elsdenii
      flavodoxin, and they provide experimental support to an earlier proposal that the
      carboxylate on its side-chain is associated with the redox-linked pKa of 5.8 in
      the hydroquinone.

PMID- 10880968
TI  - F1 and F0 connections in the bovine mitochondrial ATP synthase: the role of the
      of alpha subunit N-terminus, oligomycin-sensitivity conferring protein (OCSP) and
      subunit d.
AB  - We have studied the functional effect of limited proteolysis by trypsin of the
      constituent subunits in the native and reconstituted F1F0 complex and isolated F1
      of the bovine heart mitochondrial ATP synthase (EC 3.6.1.34). Chemical cross
      linking of oligomycin-sensitivity conferring protein (OSCP) with other subunits
      of the ATP synthase and the consequent functional effects were also investigated.
      The results obtained show that the alpha subunit N-terminus is essential for the
      correct, functional connection of F1 to F0. The alpha-subunit N-terminus contacts
      OSCP which, in turn, contacts the F0I-PVP(b) and the F0-d subunits. The N
      terminus of subunit alpha, OSCP, a segment of subunit d and the C-terminal and
      central region of F0I-PVP(b) subunits are peripherally located with respect to
      subunits gamma and delta which are completely shielded in the F1F0 complex
      against trypsin digestion. This qualifies the N-terminus of subunit alpha, OSCP,
      subunit d and F0I-PVP(b) as components of the lateral element of the stalk. These
      subunits, rather than being confined at one side of the complex which would leave
      most of the central part of the gamma subunit uncovered, surround the gamma and
      the delta subunits located in the central stalk.

PMID- 10880969
TI  - Specific Ser-Pro phosphorylation by the RNA-recognition motif containing kinase
      KIS.
AB  - We present here a first appraisal of the phosphorylation site specificity of KIS
      (for 'kinase interacting with stathmin'), a novel mammalian kinase that has the
      unique feature among kinases to possess an RNP type RNA-recognition motif (RRM).
      In vitro kinase assays using various standard substrates revealed that KIS has a
      narrow specificity, with myelin basic protein (MBP) and synapsin I being the best
      in vitro substrates among those tested. Mass spectrometry and peptide sequencing
      allowed us to identify serine 164 of MBP as the unique site phosphorylated by
      KIS. Phosphorylation of synthetic peptides indicated the importance of the
      proline residue at position +1. We also identified a tryptic peptide of synapsin
      I phosphorylated by KIS and containing a phosphorylatable Ser-Pro motif.
      Altogether, our results suggest that KIS preferentially phosphorylates proline
      directed residues but has a specificity different from that of MAP kinases and
      cdks.

PMID- 10880970
TI  - Purification and characterization of phosphoenolpyruvate carboxylase from
      Brassica napus (rapeseed) suspension cell cultures: implications for
      phosphoenolpyruvate carboxylase regulation during phosphate starvation, and the
      integration of glycolysis with nitrogen assimilation.
AB  - Phosphoenolpyruvate carboxylase (PEPC) specific activity increased by 250%
      following 8 to 10 days of Pi starvation of Brassica napus suspension cells.
      Densitometric scanning of PEPC immunoblots revealed a close correlation between
      PEPC activity and the amount of the antigenic 104-kDa PEPC subunit. To further
      assess the influence of Pi deprivation on PEPC, the enzyme was purified from Pi
      sufficient (+Pi) and Pi-starved (-Pi) cells to electrophoretic homogeneity and
      final specific activities of 37-40 micromol phosphoenolpyruvate utilized per min
      per mg protein. Gel filtration, SDS/PAGE, and CNBr peptide mapping indicated that
      the +Pi and -Pi PEPCs are both homotetramers composed of an identical 104-kDa
      subunit. Respective pH-activity profiles, phosphoenolpyruvate saturation
      kinetics, and sensitivity to L-malate inhibition were also indistinguishable.
      Kinetic studies and phosphatase treatments revealed that PEPC of the +Pi and -Pi
      cells exists mainly in its dephosphorylated (L-malate sensitive) form. Thus, up
      regulation of PEPC activity in -Pi cells appears to be solely due to the
      accumulation of the same PEPC isoform being expressed in +Pi cells. PEPC activity
      was modulated by several metabolites involved in carbon and nitrogen metabolism.
      At pH 7.3, marked activation by glucose 6-phosphate and inhibition by L-malate, L
      aspartate, L-glutamate, DL-isocitrate, rutin and quercetin was observed. The
      following paper provides a model for the coordinate regulation of B. napus PEPC
      and cytosolic pyruvate kinase by allosteric effectors. L-Aspartate and L
      glutamate appear to play a crucial role in the control of the phosphoenolpyruvate
      branchpoint in B. napus, particularly with respect to the integration of
      carbohydrate partitioning with the generation of carbon skeletons required during
      nitrogen assimilation.

PMID- 10880971
TI  - Purification and characterization of cytosolic pyruvate kinase from Brassica
      napus (rapeseed) suspension cell cultures: implications for the integration of
      glycolysis with nitrogen assimilation.
AB  - Cytosolic pyruvate kinase (PKc) from Brassica napus suspension cells was purified
      201-fold to electrophoretic homogeneity and a final specific activity of 51
      micromol phosphoenolpyruvate utilized per min per mg protein. SDS/PAGE and gel
      filtration analyses of the final preparation indicated that this PKc is a 220-kDa
      homotetramer composed of 56-kDa subunits. The enzyme was relatively heat-stable
      and displayed a broad pH optimum of pH 6.8. PKc activity was absolutely dependent
      upon the simultaneous presence of a bivalent and univalent cation, with Mg2+ and
      K+ fulfilling this requirement. Hyperbolic saturation kinetics were observed for
      phosphoenolpyruvate, ADP, Mg2+ and K+ (apparent Km values = 0.12, 0.075, 0.21 and
      0.48 mM, respectively). Although the enzyme utilized UDP, CDP and IDP as
      alternative nucleotides, ADP was the preferred substrate. L-Glutamate, oxalate,
      and the flavonoids rutin and quercetin were the most effective inhibitors (I50
      values = 4, 0.3, 0.07, and 0.10 mM, respectively). L-Aspartate functioned as an
      activator (Ka = 0.31 mM) by causing a 40% increase in Vmax while completely
      reversing the inhibition of PKc by L-glutamate. Reciprocal control by L-aspartate
      and L-glutamate is specific for these amino acids and provides a rationale for
      the in vivo activation of PKc that occurs during periods of enhanced NH +4
      assimilation. Allosteric features of B. napus PKc are compared with those of B.
      napus phosphoenolpyruvate carboxylase. A model is presented that highlights the
      pivotal role of L-aspartate and L-glutamate in the coordinate regulation of these
      key phosphoenolpyruvate utilizing cytosolic enzymes.

PMID- 10880972
TI  - Effects of hydrostatic pressure on the structure and biological activity of
      infectious bursal disease virus.
AB  - The effects of high hydrostatic pressure on the structure and biological activity
      of infectious bursal disease virus (IBDV), a commercially important pathogen of
      chickens, were investigated. IBDV was completely dissociated into subunits at a
      pressure of 240 MPa and 0 degrees C revealed by the change in intrinsic
      fluorescence spectrum and light scattering. The dissociation of IBDV showed
      abnormal concentration dependence as observed for some other viruses. Electron
      microscopy study showed that morphology of IBDV had an obvious change after
      pressure treatment at 0 degrees C. It was found that elevating pressure destroyed
      the infectivity of IBDV, and a completely pressure-inactivated IBDV could be
      obtained under proper conditions. The pressure-inactivated IBDV retained the
      original immunogenic properties and could elicit high titers of virus
      neutralizing antibodies. These results indicate that hydrostatic pressure
      provides a potential physical means to prepare antiviral vaccine.

PMID- 10880973
TI  - Immunohistochemical evidence for the myeloperoxidase/H2O2/halide system in human
      atherosclerotic lesions: colocalization of myeloperoxidase and hypochlorite
      modified proteins.
AB  - The 'oxidation theory' of atherosclerosis proposes that oxidation of low density
      lipoprotein (LDL) contributes to atherogenesis. Although the precise mechanisms
      of in vivo oxidation are widely unknown, increasing evidence suggests that
      myeloperoxidase (MPO, EC 1.11.1.7), a protein secreted by activated phagocytes,
      generates modified/oxidized (lipo)proteins via intermediate formation of
      hypochlorous acid (HOCl). In vitro generation of HOCl transforms lipoproteins
      into high uptake forms for macrophages giving rise to cholesterol-engorged foam
      cells. To identify HOCl-modified-epitopes in human plaque tissues we have raised
      monoclonal antibodies (directed against human HOCl-modified LDL) that do not
      cross-react with other LDL modifications, i.e. peroxynitrite-LDL, hemin-LDL, Cu2+
      oxidized LDL, 4-hydroxynonenal-LDL, malondialdehyde-LDL, glycated-LDL, and
      acetylated-LDL. The antibodies recognized a specific epitope present on various
      proteins after treatment with OCl- added as reagent or generated by the
      MPO/H2O2/halide system. Immunohistochemical studies revealed pronounced staining
      for HOCl-modified-epitopes in fibroatheroma (type V) and complicated (type VI)
      lesions, while no staining was observed in aortae of lesion-prone location (type
      I). HOCl-oxidation-specific epitopes are detected in cells in the majority of
      atherosclerotic plaques but not in control segments. Staining was shown to be
      inside and outside monocytes/macrophages, endothelial cells, as well as in the
      extracellular matrix. A similar staining pattern using immunohistochemistry could
      be obtained for MPO. The colocalization of immunoreactive MPO and HOCl-modified
      epitopes in serial sections of human atheroma (type IV), fibroatheroma (type V)
      and complicated (type VI) lesions provides further convincing evidence for
      MPO/H2O2/halide system-mediated oxidation of (lipo)proteins under in vivo
      conditions. We propose that MPO could act as an important link between the
      development of atherosclerotic plaque in the artery wall and chronic inflammatory
      events.

PMID- 10880974
TI  - Structure determination of [Arg8]vasopressin methylenedithioether in
      dimethylsulfoxide using NMR.
AB  - The structure of [Arg8]vasopressin methylenedithioether ([AVP]CH2) has been
      determined in dimethylsulfoxide-d6. Two-dimensional DQF-COSY and NOESY spectra
      were measured and used to derive angle and distance constraints for restrained
      molecular dynamics (MD) calculations. In the MD trajectory, two types of beta
      turn structure were found in the region from Tyr2 to Asn5, suggesting an
      equilibrium between type-I and type-II' beta-turn structures. When Halpha
      chemical shifts were used as an additional constraint, the type-I turn was
      favoured. To validate this result, an independent energy minimization procedure
      was used, using differences between calculated and observed chemical shifts. The
      two approaches gave essentially identical results. It is therefore concluded that
      the type-I turn predominates in solution. Analysis of calculated chemical shift
      contributions suggests that the beta-turn structure found in AVP is well
      preserved in [AVP]CH2, although the pressin ring size is expanded.

PMID- 10880975
TI  - Crystal structure of the disulfide bond-deficient azurin mutant C3A/C26A: how
      important is the S-S bond for folding and stability?
AB  - Azurin has a beta-barrel fold comprising eight beta-strands and one alpha helix.
      A disulfide bond between residues 3 and 26 connects the N-termini of beta strands
      beta1 and beta3. Three mutant proteins lacking the disulfide bond were
      constructed, C3A/C26A, C3A/C26I and a putative salt bridge (SB) in the
      C3A/S25R/C26A/K27R mutant. All three mutants exhibit spectroscopic properties
      similar to the wild-type protein. Furthermore, the crystal structure of the
      C3A/C26A mutant was determined at 2.0 A resolution and, in comparison to the wild
      type protein, the only differences are found in the immediate proximity of the
      mutation. The mutants lose the 628 nm charge-transfer band at a temperature 10-22
      degrees C lower than the wild-type protein. The folding of the zinc loaded
      C3A/C26A mutant was studied by guanidine hydrochloride (GdnHCl) induced
      denaturation monitored both by fluorescence and CD spectroscopy. The midpoint in
      the folding equilibrium, at 1.3 M GdnHCl, was observed using both CD and
      fluorescence spectroscopy. The free energy of folding determined from CD is -24.9
      kJ.mol-1, a destabilization of approximately 20 kJ.mol-1 compared to the wild
      type Zn2+-protein carrying an intact disulfide bond, indicating that the
      disulfide bond is important for giving azurin its stable structure. The C3A/C26I
      mutant is more stable and the SB mutant is less stable than C3A/C26A, both in
      terms of folding energy and thermal denaturation. The folding intermediate of the
      wild-type Zn2+-azurin is not observed for the disulfide-deficient C3A/C26A
      mutant. The rate of unfolding for the C3A/C26A mutant is similar to that of the
      wild-type protein, suggesting that the site of the mutation is not involved in an
      early unfolding reaction.

PMID- 10880976
TI  - Mechanism of product chain length determination for heptaprenyl diphosphate
      synthase from Bacillus stearothermophilus.
AB  - A member of the medium-chain prenyl diphosphate synthases, Bacillus
      stearothermophilus heptaprenyl diphosphate synthase, catalyzes the consecutive
      condensation of isopentenyl diphosphate with allylic diphosphate to produce (all
      E)-C35 prenyl diphosphate as the ultimate product. We previously showed that the
      product specificity of short-chain prenyl diphosphate synthases is regulated by
      the structure around the first aspartate-rich motif (FARM). The FARM is also
      conserved in a subunit of heptaprenyl diphosphate synthase, component II', which
      suggests that the structure around the FARM of component II' regulates the
      elongation. To determine whether component II' regulates the product chain length
      by a mode similar to that of the short-chain prenyl diphosphate synthases, we
      replaced a bulky amino acid at the eighth position before the FARM of component
      II', isoleucine 76, by glycine and analyzed the product specificity. The mutated
      enzyme, I76G, can catalyze condensations of isopentenyl diphosphate beyond the
      native chain length of C35. Moreover, two mutated enzymes of A79Y and S80F, which
      have a single replacement to the aromatic residue at the fourth or the fifth
      position before the FARM, mainly yielded a C20 product. These results strongly
      suggest that a common mechanism controls the product chain length of both short
      chain and medium-chain prenyl diphosphate synthases and that, in wild-type
      heptaprenyl diphosphate synthase, the prenyl chain can grow on the surface of the
      small residues at positions 79 and 80, and the elongation is precisely blocked at
      the length of C35 by isoleucine 76.

PMID- 10880977
TI  - Cross-talk between olfactory second messenger pathways.
AB  - The second messengers 3'-5'-cyclic-monophosphate (cAMP) and inositol 1,4,5
      trisphosphate (InsP3) have been implicated in olfactory signal transduction in
      various species. The results of the present study provide evidence that the two
      olfactory second messenger pathways in rat olfactory neurons do not work
      independently but rather show a functional antagonism: whereas inhibition of
      phospholipase C (PLC) in isolated olfactory cilia by U-73122 led to an
      augmentation of odor-induced cAMP signaling, activation of the phosphoinositol
      pathway resulted in attenuation of odor-induced cAMP formation. Furthermore, this
      study indicates that elevated cAMP levels cause suppression of odor-induced InsP3
      signaling, whereas inhibition of adenylate cyclase (AC) by cisN-(2
      phenylcyclopentyl)azacylotridec-1-en-2-amine (MDL-12,330 A) results in
      potentiation of odor-induced InsP3 formation. Concerning the molecular mechanism
      involved in cross-interaction, the experimental data indicate that the observed
      antagonism of elevated cAMP is based on inhibition of PLC activation rather than
      on stimulation of InsP3 degradation. As blockage of the endogenous protein kinase
      A (PKA) prevented the inhibitory effect of cAMP, the suppression of odor-induced
      InsP3 signaling by cAMP may be mediated by a PKA-controlled reaction.

PMID- 10880978
TI  - Alternative splicing generates a family of putative secreted and membrane
      associated MUC4 mucins.
AB  - The MUC4 mucin gene encodes a putative membrane-anchored mucin with predicted
      size of 930 kDa, for its 26.5-kb allele. It is composed of two regions, the 850
      kDa mucin-type subunit MUC4alpha and the 80-kDa membrane-associated subunit
      MUC4beta. In this study, we cloned and characterized unique MUC4 cDNA sequences
      that differ from the originally published sequence. Eight alternative splice
      events located downstream of the central large tandem repeat array generated
      eight new, distinct cDNAs. The deduced sequences of these MUC4 cDNAs (sv1-MUC4 to
      sv8-MUC4, the full length cDNA being called sv0-MUC4) provided seven distinct
      variants, five secreted forms and two membrane-associated forms. Furthermore, two
      other alternative splicing events located on both sides of the tandem repeat
      array created two variants, MUC4/Y and MUC4/X, both lacking the central tandem
      repeat. Therefore, MUC4 can be expressed in three distinct forms, one membrane
      bound, one secreted, and one lacking the hallmark feature of mucin, the tandem
      repeat array. Although no specific function has yet been discovered for the
      family of proteins putatively produced from the unique MUC4 gene, we suspect that
      the MUC4 proteins may be implicated in the integrity and renewal of the
      epithelium.

PMID- 10880979
TI  - Structure/thermodynamics relationships of lectin-saccharide complexes: the
      Erythrina corallodendron case.
AB  - Molecular dynamics (MD) simulations of Erythrina corallodendron lectin binding to
      a monosaccharide, alpha-galactose, and a disaccharide, N-acetyl lactosamine, have
      been performed in order to investigate the relationship between structure and
      thermodynamics. A simulated annealing protocol has been used to generate
      ensembles of structures for the two complexes, from which both qualitative and
      quantitative information on binding dynamics have been extracted. The ensembled
      averaged lectin-saccharide interaction enthalpy is equivalent for both sugars,
      whereas the calculation based on the X-ray structures does show a difference.
      Within large statistical errors, the calculated 'binding enthalpy' is also the
      same for the two systems. These errors arise largely from terms involving solvent
      and are a typical limitation of current MD simulations. Significant qualitative
      differences in binding between the two complexes are, however, observed over the
      ensembles. These could be important for unraveling the structure/thermodynamic
      relationship. Stated simply, there are a greater number of binding options
      available to the disaccharide compared to the monosaccharide. The implications of
      alternative binding states on thermodynamic parameters and the 'breaking of
      enthalpy-entropy compensation' are discussed. The role of solvent in lectin
      saccharide complex formation is suggested to be significant.

PMID- 10880980
TI  - Evidence that the lizard helospectin peptides are O-glycosylated.
AB  - Six forms of helospectin (a vasoactive intestinal peptide analogue) were purified
      from the venom of the Heloderma horridum lizard. Their identification was
      performed by combining sequencing by automated Edman degradation and electrospray
      mass spectrometry analysis on the complete peptides and their tryptic fragments.
      The products resulting from the action of an O-glycosidase were also analysed.
      Two forms were identified as the previously named Hs1 and Hs2 of 38 and 37 amino
      acid residues, respectively. Two forms corresponded to Hs1 and Hs2 O-glycosylated
      by a N-acetylhexosamine-hexose motif attached to the Ser32 residue. Two other
      forms were not completely characterized but might correspond to the O
      glycosylated forms bearing a phosphate or a sulfate group. The glycosylation did
      not affect the capacity of the helospectins to recognize and to activate the
      human and the rat VPAC1 and VPAC2 receptors.

PMID- 10880981
TI  - Kiwi protein inhibitor of pectin methylesterase amino-acid sequence and
      structural importance of two disulfide bridges.
AB  - A protein acting as a powerful inhibitor of plant pectin methylesterase was
      isolated from kiwi (Actinidia chinensis) fruit. The complete amino-acid sequence
      of the pectin methylesterase inhibitor (PMEI) was determined by direct protein
      analysis. The sequence comprises 152 amino-acid residues, accounting for a
      molecular mass of 16 277 Da. The far-UV CD spectrum indicated a predominant alpha
      helix conformation in the secondary structure. The protein has five cysteine
      residues but neither tryptophan nor methionine. Analysis of fragments obtained
      after digestion of the protein alkylated without previous reduction identified
      two disulfide bridges connecting Cys9 with Cys18, and Cys74 with Cys114; Cys140
      bears a free thiol group. A database search pointed out a similarity between PMEI
      and plant invertase inhibitors. In particular, the four Cys residues, which in
      PMEI are involved in the disulfide bridges, are conserved. This allows us to
      infer that also in the homologous proteins, whose primary structure was deduced
      only by cDNA sequencing, those cysteine residues are engaged in two disulfide
      bridges, and constitute a common structural motif. The comparison of the sequence
      of these inhibitors confirms the existence of a novel class of proteins with
      moderate but significant sequence conservation, comprising plant proteins acting
      as inhibitors of sugar metabolism enzymes, and probably involved in various steps
      of plant development.

PMID- 10880982
TI  - Reconstitution of ethanolic fermentation in permeabilized spheroplasts of wild
      type and trehalose-6-phosphate synthase mutants of the yeast Saccharomyces
      cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, TPS1-encoded trehalose-6-phosphate
      synthase (TPS) exerts an essential control on the influx of glucose into
      glycolysis, presumably by restricting hexokinase activity. Deletion of TPS1
      results in severe hyperaccumulation of sugar phosphates and near absence of
      ethanol formation. To investigate whether trehalose 6-phosphate (Tre6P) is the
      sole mediator of hexokinase inhibition, we have reconstituted ethanolic
      fermentation from glucose in permeabilized spheroplasts of the wild-type,
      tps1Delta and tps2Delta (Tre6P phosphatase) strains. For the tps1Delta strain,
      ethanol production was significantly lower and was associated with
      hyperaccumulation of Glu6P and Fru6P. A tps2Delta strain shows reduced
      accumulation of Glu6P and Fru6P both in intact cells and in permeabilized
      spheroplasts. These results are not consistent with Tre6P being the sole mediator
      of hexokinase inhibition. Reconstitution of ethanolic fermentation in
      permeabilized spheroplasts with glycolytic intermediates indicates additional
      target site(s) for the Tps1 control. Addition of Tre6P partially shifts the
      ethanol production rate and the metabolite pattern in permeabilized tps1Delta
      spheroplasts to those of the wild-type strain, but only with glucose as
      substrate. This is observed at a very high ratio of glucose to Tre6P. Inhibition
      of hexokinase activity by Tre6P is less efficiently counteracted by glucose in
      permeabilized spheroplasts compared to cell extracts, and this effect is largely
      abolished by deletion of TPS2 but not TPS1. In permeabilized spheroplasts,
      hexokinase activity is significantly lower in a tps2Delta strain compared to a
      wild-type strain and this difference is strongly reduced by additional deletion
      of TPS1. These results indicate that Tps1-mediated protein-protein interactions
      are important for control of glucose influx into yeast glycolysis, that Tre6P
      inhibition of hexokinase might not be competitive with respect to glucose in vivo
      and that also Tps2 appears to play a role in the control of hexokinase activity.

PMID- 10880983
TI  - The structure of the carbohydrate backbone of the lipopolysaccharides from
      Bordetella hinzii and Bordetella bronchiseptica.
AB  - The structure of the core-lipid A region of the lipopolysaccharides from
      Bordetella hinzii and Bordetella bronchiseptica has been analyzed.
      Lipopolysaccharides were deacylated using strong alkaline hydrolysis, the
      products were separated by high performance anion-exchange chromatography and
      analyzed by NMR and mass spectrometry. The following structure of the products
      can be deduced from the experimental results: where for the product from
      Bordetella hinzii N = H, R = H, beta-FucN4N- or partially N-acetylated Sug-(1-3)
      beta-FucN4N and for the product from Bordetella bronchiseptica N = alpha-Hep, R =
      H, beta-FucN4N, beta-FucN4NMe or partially N-acetylated Sug-(1-3)-beta-FucN4N or
      Sug-(1-3)-beta-FucN4NMe; Sug = 2,3-diamino-2,3, 4-trideoxy-hex-4
      enuronopyranosyl.

PMID- 10880984
TI  - Isolation of dermatoxin from frog skin, an antibacterial peptide encoded by a
      novel member of the dermaseptin genes family.
AB  - A 32-residue peptide, named dermatoxin, has been extracted from the skin of a
      single specimen of the tree frog Phyllomedusa bicolor, and purified to
      homogeneity using a four-step protocol. Mass spectral analysis and sequencing of
      the purified peptide, as well as chemical synthesis and cDNA analysis were
      consistent with the structure: SLGSFLKGVGTTLASVGKVVSDQF GKLLQAGQ. This peptide
      proved to be bactericidal towards mollicutes (wall-less eubacteria) and Gram
      positive eubacteria, and also, though to a lesser extent, towards Gram-negative
      eubacteria. Measurement of the bacterial membrane potential revealed that the
      plasma membrane is the primary target of dermatoxin. Observation of bacterial
      cells using reflected light fluorescence microscopy after DNA-staining was
      consistent with a mechanism of cell killing based upon the alteration of membrane
      permeability rather than membrane solubilization, very likely by forming ion
      conducting channels through the plasma membrane. CD spectroscopy and secondary
      structure predictions indicated that dermatoxin assumes an amphipathic alpha
      helical conformation in low polarity media which mimic the lipophilicity of the
      membrane of target microorganisms. PCR analysis coupled with cDNA cloning and
      sequencing revealed that dermatoxin is expressed in the skin, the intestine and
      the brain. Preprodermatoxin from the brain and the intestine have the same
      sequence as the skin preproform except for two amino-acid substitutions in the
      preproregion of the brain precursor. The dermatoxin precursor displayed the
      characteristic features of preprodermaseptins, a family of peptide precursors
      found in the skin of Phyllomedusa ssp. Precursors of this family have a common N
      terminal preproregion followed by markedly different C-terminal domains that give
      rise to 19-34-residue peptide antibiotics named dermaseptins B and phylloxin, and
      to the D-amino-acid-containing opioid heptapeptides dermorphins and deltorphins.
      Because the structures and cidal mechanisms of dermatoxin, dermaseptins B and
      phylloxin are very different, dermatoxin extends the repertoire of structurally
      and functionally diverse peptides derived from the rapidly evolving C-terminal
      domains of precursors of the dermaseptins family.

PMID- 10880985
TI  - Role of redox-active iron ions in the decomposition of S-nitrosocysteine in
      subcellular fractions of porcine aorta.
AB  - We recently reported that degradation of S-nitrosocysteine in homogenates of
      porcine aorta increased severalfold in the presence of Mg2+ ions [Kostka, P., Xu,
      B. & Skiles, E.H. (1999) J. Cardiovasc. Pharmacol. 33, 665-670]. The objective of
      the present study was to examine this in greater detail. The rate of S
      nitrosocysteine degradation by aortic homogenates in the presence of Mg2+ ions
      exhibited differential sensitivity to chelators of iron ions. Terpyridine and
      diethylenetriamine penta-acetic acid (5-500 microM) caused a concentration
      dependent inhibition of S-nitrosocysteine decay, whereas deferoxamine (100
      microM) was ineffective. o-Phenanthroline (250 microM), a selective chelator of
      Fe2+ ions, potentiated the reaction at low initial concentrations of S
      nitrosocysteine (< or = 15 microM) and inhibited the reaction at higher
      concentrations. The inhibitory effects of o-phenanthroline were related to
      suppression of S-nitrosocysteine decay by cysteine-mediated reduction of Fe3+. In
      the presence of o-phenanthroline, S-nitrosocysteine decomposition followed
      saturable kinetics with K0.5 = 3.8 +/- 0.3 microM and h = 1.8 +/- 0.1 (mean +/-
      SE, n = 4). Comparison of the rates of S-nitrosocysteine decay in different
      subcellular fractions showed selective association with the cytosolic fraction,
      as documented by copurification with lactate dehydrogenase activity. At non
      limiting concentrations of S-nitrosocysteine, the rate of degradation in the
      cytosolic fraction was 4.1 +/- 0.3 nmol.min-1.(mg protein)-1 (n = 4). It is
      concluded that the cytosolic fraction of porcine aorta contains a protein factor,
      presumably an enzyme, capable of catalyzing heterolytic decomposition of the S-NO
      bond of S-nitrosocysteine in a process involving redox cycling of iron ions.

PMID- 10880986
TI  - Sex hormones and pain: a new role for brain aromatase?

PMID- 10880987
TI  - Localization and controls of aromatase in the quail spinal cord.
AB  - In adult male and female Japanese quail, aromatase-immunoreactive cells were
      identified in the spinal dorsal horns from the upper cervical segments to the
      lower caudal area. These immunoreactive cells are located mostly in laminae I
      III, with additional sparse cells being present in the medial part of lamina V
      and, at the cervical level exclusively, in lamina X around the central canal.
      Radioenzyme assays based on the measurement of tritiated water release confirmed
      the presence of substantial levels of aromatase activity throughout the
      rostrocaudal extent of the spinal cord. Contrary to what is observed in the
      brain, this enzyme activity and the number of aromatase-immunoreactive cells in
      five representative segments of the spinal cord are not different in sexually
      mature males or females and are not influenced in males by castration with or
      without testosterone treatment. The aromatase activity and the numbers of
      aromatase-immunoreactive cells per section are higher at the brachial and
      thoracic levels than in the cervical and lumbar segments. These experiments
      demonstrate for the first time the presence of local estrogen production in the
      spinal cord of a higher vertebrate. This production was localized in the sensory
      fields of the dorsal horn, where estrogen receptors have been identified
      previously in several avian and mammalian species, suggesting an implication of
      aromatase in the modulation of sensory (particularly nociceptive) processes.

PMID- 10880988
TI  - Expression of semaphorins in developing and regenerating olfactory epithelium.
AB  - Semaphorins provide signals that guide growing axons to their appropriate
      destinations. The secreted semaphorin, Sema3A, mediates repulsive effects on
      axons from various neuronal populations in embryonic rats. The authors localized
      Sema3A mRNA expression in the primary olfactory pathway during development, in
      adult rats, and in adult rats that were subjected to a unilateral olfactory
      bulbectomy. Developing rats at ages from embryonic day 14 (E14) to E19 expressed
      Sema3A in the olfactory receptor neurons (ORNs) of the olfactory epithelium and
      in chondrogenic structures surrounding the nasal cavity. In vitro, ORN axons at
      E14 avoided substrate-bound Sema3A. Low levels of Sema3A expression persisted in
      the normal adult epithelium both in ORNs scattered throughout the epithelium and
      in small clusters. Three days after a unilateral olfactory bulbectomy, Sema3A
      transcript levels increased in regenerating neurons. High levels of Sema3A
      transcript were found at 1 week postbulbectomy, persisted for 2 weeks, and
      diminished by 3 weeks. Several other murine semaphorins (Sema4A, Sema4B, and
      Sema4C) were expressed differentially in the primary olfactory pathway both
      during development and regeneration. These findings suggest that Sema3A and
      perhaps other semaphorins play a role in directing ORNs out of the epithelium and
      to the olfactory bulb, their target structure, during both development and
      regeneration.

PMID- 10880989
TI  - Disruption of the gene encoding SF-1 alters the distribution of hypothalamic
      neuronal phenotypes.
AB  - The ventromedial nucleus of the hypothalamus (VMH) in mice first emerges as a
      histologically distinct cell cluster around embryonic day 17 (E17). The earliest
      known marker for cells destined to form the VMH is the orphan nuclear receptor,
      steroidogenic factor 1 (SF-1), which can be detected in the hypothalamic
      primordium by E11. Strikingly, the VMH is absent in newborn SF-1 knockout mice,
      suggesting that SF-1 is essential for the development of VMH neurons. We reported
      previously that the VMH can be identified before it emerges as a histologically
      distinct nucleus (i.e., at E13) by the exclusion of cells that are immunoreactive
      for both gamma-aminobutyric acid (GABA) and the synthetic enzyme, glutamic acid
      decarboxylase (GAD67). Subsequently, by E15, the developing VMH is demarcated
      further by cells that are immunoreactive for neuropeptide Y, estrogen receptor
      alpha (ERalpha), and galanin. It is noteworthy that the normal exclusion of GABA
      from the developing VMH is not seen in SF-1 knockout mice, and cells that are
      immunoreactive for neuropeptide Y, ERalpha, and galanin also are distributed
      aberrantly in this region. Thus, the absence of SF-1 profoundly affects the
      cellular architecture of the VMH from early stages in its formation. These data
      suggest that, directly or indirectly, SF-1 plays important roles in determining
      the distribution of cells in the mediobasal hypothalamus.

PMID- 10880990
TI  - Diffuse distribution of sulforhodamine-labeled neurons during serotonin-evoked
      locomotion in the neonatal rat thoracolumbar spinal cord.
AB  - The fluorescent dye sulforhodamine-101 undergoes synaptic activity-dependent
      endocytotic uptake and consequent retrograde transport in presynaptic neurons. We
      used sulforhodamine to identify thoracolumbar spinal premotor neurons (T11-L6)
      activated during serotonin (5-HT) -induced hindlimb locomotor-like activity in
      the in vitro neonatal rat spinal cord preparation. Sulforhodamine labeling
      required locomotor-like activity because few neurons were labeled unless bath
      applied 5-HT recruited the locomotor rhythm. In contrast, N-methyl-D-aspartate
      (NMDA; 5 microM) profoundly increased spinal neuronal labeling irrespective of
      locomotor activity. The contribution of false-positive activity labeling during
      locomotion induced by application of NMDA with 5-HT (Kjaerulff et al. [1994] J
      Physiol (Lond). 478:265-273) necessitated the present re-mapping of
      sulforhodamine-labeled neurons. During 5-HT-evoked locomotion, the sulforhodamine
      labeled neurons were diffusely scattered within the spinal cord with predominant
      labeling in lamina VII. Motor nuclei (lamina IX) and superficial laminae (I-II)
      were typically devoid of labeled cells in the isolated spinal cord. However,
      unilateral labeling of motoneurons was achieved when the ipsilateral hindlimb
      remained attached, suggesting that uptake in motoneurons requires an intact
      neuromuscular junction. The rostrocaudal incidence and distribution of labeled
      neurons was uniform in spinal segments L1-L5, with reduced numbers observed in
      thoracic and L6 spinal segments. Mean total cell labeling was less than 400 per
      spinal segment, suggesting recruitment from a very small fraction of the neurons
      contained within the spinal cord (calculated at < 0.1%). These results are
      consistent with the limited transfer of locomotor-related synaptic activity
      (Raastad et al. [1996] Neuron 17:729-738) and severe synaptic fatigue (Lev-Tov
      and Pinco [1992] J Physiol. 447:149-169; Pinco and Lev-Tov [1993] J Neurophysiol.
      70:1151-1158; Fleoter and Lev-Tov [1993] J Neurophysiol. 70:2241-2250) observed
      in the neonatal rat spinal cord.

PMID- 10880992
TI  - Distribution and regulation of telencephalic aromatase expression in the zebra
      finch revealed with a specific antibody.
AB  - In songbirds, aromatase (estrogen synthase) activity and mRNA are readily
      detectable in the brain. This neural aromatization presumably provides estrogen
      to steroid-sensitive targets via autocrine, paracrine, and synaptic mechanisms.
      The location of immunoreactive protein, however, has been difficult to describe
      completely, particularly in distal dendrites, axons, and terminals of the
      forebrain. Here we describe the neuroanatomical distribution of aromatase in the
      zebra finch by using a novel antibody raised specifically against zebra finch
      aromatase. The distribution of aromatase-positive somata in the zebra finch brain
      is in excellent agreement with previous reports. Additionally, this antibody
      reveals elaborate, spinous dendritic arbors, fine-beaded axons, and punctate
      terminals of telencephalic neurons that may synthesize estrogen. Some of these
      axon-like fibers extend into the high vocal center (HVC) and the robust nucleus
      of the archistriatum (RA) in males and females, suggesting a role for presynaptic
      aromatization in cellular processes within these loci. Adult males have more
      aromatase-positive fibers in the caudomedial neostriatum (NCM) and the preoptic
      area (POA) compared to females, despite the lack of detectable sex differences in
      the number of immunoreactive somata at these loci. Thus, the compartmentalization
      of aromatase in dendrites and axons may serve a sexually dimorphic function in
      the songbird. Finally, in adult males, aromatase expression is down-regulated by
      circulating estradiol in the hippocampus, but not in the NCM or POA. The
      distribution of aromatase suggests a role for aromatization in the regulation of
      pre- and postsynaptic function in steroid sensitive areas of the songbird
      forebrain.

PMID- 10880993
TI  - Spinomedullary pathways in the pigeon (Columba livia): differential involvement
      of lamina I cells.
AB  - The lamina I (marginal zone) of the spinal cord dorsal horn is an important site
      for pain processing. In mammals, lamina I neurons have been shown to constitute a
      heterogeneous population made up of four morphological groups with particular
      neurochemical nature, supraspinal connection patterns, and nociceptive response
      properties. In order to obtain a comparative view of the mechanisms of
      nociceptive processing, the analysis of the structural morphology and supraspinal
      connectivity of lamina I neurons was, in this study, extended to the avian
      family. Cholera toxin subunit B (CTb) was injected in the nucleus tractus
      solitarius (NTS), nucleus centralis medullae pars dorsalis (Cnd), and the
      dorsolateral portion of the nucleus reticularis lateralis (RLlat) of the pigeon
      (Columba livia), areas equivalent to the rat caudal medulla oblongata lamina I
      targets, which have been shown to receive differential projections from all cell
      groups present in lamina I of mammals. In the pigeon, lamina I cells project to
      the three medullary regions and present the same morphology of spinomedullary
      lamina I cells of mammals: the spinal-NTS and the spinal-RLlat pathways
      originated from fusiform, pyramidal, and flattened neurons, and the spinal-Cnd
      pathway from multipolar, pyramidal, and flattened neurons. Furthermore, the
      relative participation of each lamina I cell type in each pathway was found to be
      similar to that previously observed in the rat. The observed similarities on the
      anatomical organization of lamina I neurons in mammalian and avian species can be
      taken as a phylogenetic indication of the importance of the nociceptive circuitry
      centered in lamina I.

PMID- 10880991
TI  - Distribution and development of nicotinic acetylcholine receptor subtypes in the
      optic tectum of Rana pipiens.
AB  - Acetylcholine allows the elicitation of visually evoked behaviors mediated by the
      frog optic tectum, but the mechanisms behind its effects are unknown. Although
      nicotinic acetylcholine receptors (nAChRs) exist in the tectum, their subtype has
      not been assessed. By using quantitative autoradiography, we examined the binding
      of [(3)H]cytisine and [(125)I]alpha-bungarotoxin in the laminated tectum. In
      mammalian systems, these radioligands bind with high affinity to alpha4 nAChR
      subunits and alpha7 nAChR subunits, respectively. [(3)H]Cytisine demonstrated
      high specific binding in adult frogs in retinorecipient layer 9, intermediate
      densities in layer 8, and low binding in layers 1-7 of the tectum. [(3)H]Cytisine
      binding was significantly higher in the tecta of adults than in those of
      tadpoles. Lesioning the optic nerve for 6 weeks decreased [(3)H]cytisine binding
      in layers 8/9 by 70+/-1%, whereas 6-month lesions decreased binding by 76+/-3%.
      Specific binding of [(125)I]alpha-bungarotoxin in adults was present only at
      intermediate levels in tectal layers 8 and 9, and undetectable in the deeper
      tectal layers. However, the nucleus isthmi, a midbrain structure reciprocally
      connected to the tectum, exhibited high levels of binding. There were no
      significant differences in tectal [(125)I]alpha-bungarotoxin binding between
      tadpoles and adults. Six-week lesions of the optic nerve decreased tectal
      [(125)I]alpha-bungarotoxin binding by 33+/-10%, but 6-month lesions had no
      effect. The pharmacokinetic characteristics of [(3)H]cytisine and [(125)I]alpha
      bungarotoxin binding in the frog brain were similar to those demonstrated in
      several mammalian species. These results indicate that [(3)H]cytisine and
      [(125)I]alpha-bungarotoxin identify distinct nAChR subtypes in the tectum that
      likely contain non-alpha7 and alpha7 subunits, respectively. The majority of non
      alpha7 receptors are likely associated with retinal ganglion cell terminals,
      whereas alpha7-containing receptors appear to have a different localization.

PMID- 10880994
TI  - Basic fibroblast growth factor applied to the optic nerve after injury increases
      long-term cell survival in the frog retina.
AB  - The neuroprotective effects of basic fibroblast growth factor (bFGF) on the long
      term survival of axotomized retinal ganglion cells (RGCs) were studied in the
      frog Rana pipiens. Cell loss was quantified in different regions of the ganglion
      cell layer using Nissl staining and tetramethylrhodamine dextran amine
      backfilling. All regions of the retina showed a significant decrease (32-66%) in
      RGC numbers between 4 and 16 weeks after axotomy. Some cells showed morphological
      and biochemical signs of apoptosis. A single application of bFGF to the optic
      nerve stump at the time of axotomy protected many of the cells 6 weeks after the
      injury, but this effect was lost by 12 weeks. A second application of bFGF, 6
      weeks after the injury, rescued many RGCs at 12 weeks. In contrast, single or
      double injections of bFGF into the eyeball had no effect on RGC survival.
      Axotomized RGCs were significantly enlarged and elongated after axotomy, and
      these morphological changes were increased by bFGF treatment. In the normal
      retina and optic nerve, immunocytochemical staining showed bFGF-like
      immunoreactivity (-LI) in the pigment epithelial layer, in the outer segments of
      photoreceptors, and in occasional RGCs. Strong bFGF-LI was present in Muller
      cells and in optic nerve astrocytes and oligodendrocytes. FGF receptor-LI was
      present in photoreceptors, outer plexiform layer, retinal ganglion cell axons,
      and Muller cells. FGF receptor-LI was also observed in optic nerve glia.

PMID- 10880995
TI  - Response of macrophage/microglial cells to experimental neuronal degeneration in
      the avian isthmo-optic nucleus during development.
AB  - Blockade of the retrograde axonal transport of isthmo-optic nucleus (ION) neurons
      in the avian embryo results in their massive degeneration. We used this system to
      investigate the response of macrophage/microglial cells to neuronal degeneration
      in the embryonic brain. Colchicine was injected into the right eye of quail or
      chick embryos at a time when the survival of ION neurons depends on retrograde
      trophic support from the retina, and the chronology of the subsequent
      macrophage/microglial response in the ION was analyzed. This response was
      restricted to the ION contralateral to the injected eye; no modifications of the
      normal state were observed in the surrounding parenchyma or in the opposite ION,
      used as control. The response was first detected 18 hours after the colchicine
      injection (18 hours pi), when an increase of the macrophage/microglial cell
      number was evident. The number of these cells in the affected ION increased,
      peaking at 40-48 hours pi. At later survival times, macrophage/microglial cells
      were progressively less abundant in the affected ION, which gradually diminished
      in size. At 120 hours pi the only remnant of the ION was a small cluster of
      macrophage/microglial cells, surrounded by a clear area with scarce nonmicroglial
      cells, in the region formerly occupied by the ION. This study reveals that a
      strong macrophage/microglial response occurs in the embryonic brain in response
      to neuronal degeneration but that these cells do not trigger the neuronal death,
      as they only appear after pyknotic fragments are already observable.

PMID- 10880996
TI  - Importance of endogenous nitric oxide synthase in the rat hypothalamus and
      amygdala in mediating the response to capsaicin.
AB  - Although capsaicin has been shown to activate certain neuronal groups in the
      hypothalamus and amygdala, the neurotransmitters involved and the exact mechanism
      of action are not clearly understood at present. The aim of this study was to
      examine the hypothesis that the effect of capsaicin in the rat hypothalamus and
      amygdala primarily involves direct activation of the endogenous nitric oxide
      synthase (NOS) neurons responsible for the synthesis of nitric oxide (NO).
      Subcutaneous capsaicin injection in male rats, compared with vehicle, caused a
      significant increase in Fos expression in the paraventricular nucleus (PVN),
      supraoptic nucleus (SON), and medial and cortical amygdala. The expression of
      nicotinamide adenine dinucleotide phosphate diaphorase, a histochemical marker
      for NOS, was also increased in these brain areas in addition to the
      periventricular and lateral hypothalamic area and central amygdaloid nucleus.
      Also, capsaicin significantly increased the expression of neuronal NOS messenger
      RNA and protein in the PVN, SON, and medial amygdala as demonstrated by in situ
      hybridization and immunohistochemistry, respectively. A higher proportion of the
      NOS neurons in the PVN, periventricular region, SON and amygdala showed Fos
      expression in response to capsaicin than vehicle injection. There was little, if
      any, Fos activation in the NOS-positive neurons in the lateral hypothalamic area.
      The capsaicin-induced activation of the hypothalamic PVN and SON neurons and the
      medial amygdaloid nucleus was attenuated in the NOS inhibitor N(omega)-nitro-L
      arginine methyl ester (L-NAME) -pretreated animals in comparison with the
      inactive enantiomer D-NAME. These observations indicate that activation of the
      endogenous NOS system and production of NO constitute a major pathway through
      which capsaicin exerts its effect within the hypothalamus and amygdala.

PMID- 10880997
TI  - Olfactory bulb and retrobulbar regions in the hedgehog tenrec: organization and
      interconnections.
AB  - The Madagascan lesser hedgehog tenrec (Echinops telfairi) is a terrestrial,
      nocturnal insectivore with a low encephalization index and a huge olfactory bulb.
      To gain insight into the organization and evolution of olfactory regions in
      placental mammals, the cytoarchitecture (Nissl), neurochemical attributes [zinc
      and acetylcholinesterase stain, nicotinamide adenine dinucleotide phosphate
      (NADPh)-diaphorase, and calcium-binding proteins], and interconnections
      (injections of wheat germ agglutinin-horseradish peroxidase and biotinylated
      dextran amine) of tenrec bulbar and retrobulbar regions were examined. The tenrec
      has a well-laminated main olfactory bulb, and modified (atypical) glomeruli are
      found that, to date, have been demonstrated only in murine rodents. Compared with
      the main olfactory bulb, the accessory bulb is relatively small, with clearly
      different staining characteristics, particularly with respect to NADPh
      diaphorase, anticalbindin, and anticalretinin. External and central anterior
      olfactory nuclei also show characteristic cytoarchitectural and
      chemoarchitectural features. The medial olfactory peduncle seems to differ
      considerably from that in rodents. A small taenial structure can be separated
      from the hippocampal continuation. This taenia tecti presumably corresponds to
      the superior part of the tenia tecti in rodents, but no homologue of the rodent's
      prominent inferior taenia tecti could be found. The connections of bulbar and
      retrobulbar regions are similar to those seen in other mammals. Interbulbar
      projection systems connect the two olfactory bulbs through an external
      (topographic) and central (nontopographic) anterior nucleus; however, the
      topographic arrangement of the intrabulbar association system seems to differ
      from that seen in rodents. A reciprocity of direct olfactory bulb connections
      with the frontal (sulcal/orbital) cortex was found in the tenrec that has not
      been reported so far in other species.

PMID- 10880998
TI  - Basal telencephalic regions connected with the olfactory bulb in a Madagascan
      hedgehog tenrec.
AB  - In an attempt to gain insight into the organization and evolution of the basal
      forebrain, the region was analysed cytoarchitecturally, chemoarchitecturally, and
      hodologically in a lower placental mammal, the lesser hedgehog tenrec. Particular
      emphasis was laid on the subdivision of the olfactory tubercle, the nuclear
      complex of the diagonal band, and the cortical amygdala. The proper tubercule and
      the rostrolateral tubercular seam differed from each other with regard to their
      immunoreactivity to calbindin and calretinin, as well as their afferents from the
      piriform cortex. Interestingly, the tubercular seam showed similar properties to
      the dwarf cell compartment, located immediately adjacent to the islands of
      Calleja. The most prominent input to the olfactory bulb (OfB) originated from the
      diagonal nuclear complex. This projection was ipsilateral, whereas the bulbar
      afferents from the hypothalamus and the mesopontine tegmentum were bilateral. The
      amygdala projected only sparsely to the OfB, but received a prominent bulbar
      projection. An exception was the nucleus of the lateral olfactory tract, which
      was poorly connected with the OfB. Unlike other species with an accessory OfB,
      the projections from the tenrec's main OfB did not show a topographic
      organization upon the lateral and medial olfactory amygdala. However, there was
      an accessory amygdala, which could be differentiated from the lateral nuclei by
      its intense reaction to NADPh-diaphorase. This reaction was poor in the diagonal
      nuclear complex as in monkey but unlike in rat. The variability of cell
      populations and olfactory bulb connections shown here may help to clarify both
      phylogenetic relationships and the significance of individual basal telencephalic
      subdivisions.

PMID- 10880999
TI  - Changing pattern of expression of parvalbumin immunoreactivity during human fetal
      spinal cord development.
AB  - Expression of the calcium binding protein parvalbumin (PV) by different classes
      of spinal neuron has been shown to be developmentally regulated in both rat and
      monkey. From postmortem studies of eight human cervical spinal cords ranging in
      age from 11 to 35 weeks postconceptional age, we report that parvalbumin
      immunoreactivity is similarly plastic in human lower cervical spinal cord
      development, with many changes occurring prenatally. At 11-14 weeks
      postconceptional age, there was prominent immunostaining of primary sensory
      afferents that could be seen coursing through the dorsal horn and extensively
      innervating the motoneuron pools. Motoneurons were also found to be clearly
      immunoreactive for choline acetyltransferase by this age. A few ventral horn
      neurons that were not motoneurons were also parvalbumin immunoreactive. By 24-27
      weeks postconceptional age, sensory afferents were still immunoreactive, as were
      many other axons throughout the white matter. In addition, many ventral horn
      neurons were now immunoreactive as well as a few dorsal horn neurons. By 31-35
      weeks postconceptional age, there was extensive immunostaining of neurons
      throughout the spinal cord, including a few moderately immunoreactive
      motoneurons. There were many immunopositive axons in all the white matter tracts
      except the corticospinal tracts; however, staining of sensory axons traversing
      the grey matter was less prominent by this age. In the rat, expression of PV by
      primary sensory neurons coincides with the onset of fetal limb movement. The
      onset of expression of PV in ventral horn neurons coincides with later
      developmental events after the arrival of corticospinal inputs, whereas
      widespread PV immunoreactivity in dorsal horn neurons marks the attainment of a
      mature pattern of PV expression. The extent to which expression of PV
      immunoreactivity can be taken to indicate landmarks in human development will be
      discussed.

PMID- 10881000
TI  - Long-term results of CD34(+) cell transplantation in children with neuroblastoma.
AB  - BACKGROUND: This is the first report of the long-term results of CD34(+) cell
      transplantation in children with neuroblastoma. We investigated the hematologic
      and immune recovery, posttransplant morbidity, and clinical outcome of these
      children. PROCEDURE: Twenty-three children with advanced neuroblastoma had PBPCs
      (20 patients) or BM (3 patients) collected, followed by CD34(+) cell selection on
      Ceprate column. The purge of residual neuroblastoma cells was evaluated using an
      RT-PCR for tyrosine hydroxylase (TH) mRNA assay. Reinfusion of CD34(+) cells
      followed busulfan + melphalan myeloablative chemotherapy. RESULTS: A median of
      2.9 x 10(6) CD34(+) cells/kg was reinjected. Median days to achieve ANC > 0.5 x
      10(9)/liter and platelets > 50 x 10(9)/liter were 13 (range 9-33) and 59 (range
      22-259), respectively. Circulating T cells were primarily CD4(-)/CD8(+) with
      fewer than 0.2 10(9)CD4(+) cells/liter throughout the first 6 months. CD19(+)
      cells and CD56(+) cells were not detectable up to day +35 posttransplant. At 1
      year posttransplant, 16 evaluable patients had stable hematopoiesis with 2.3 x
      10(9) ANC/liter (range 0.8-4.1), 1.4 x 10(9) lymphocytes/liter (range 0.5- 2.0)
      and 251 x 10(9) PLT/liter (range 35-490). After the completion of hematopoietic
      reconstitution, six events of severe septicemia/septic shock were noted. Six
      children had severe VZV infections, and 2 had EBV-associated lymphoproliferation.
      Thirteen patients are alive with a median follow-up of 40 months (range 2-54).
      Ten patients have died; 8 relapsed or developed progressive disease, 1 died from
      nondocumented pneumopathy at day 56, and 1 developed AML-M4 at 3 years
      posttransplant. CONCLUSIONS: In children, CD34(+) cell transplantation can be
      accomplished with a reduction of neuroblastoma cell inoculum in the selected
      graft as assessed by RT-PCR analysis. CD34(+) cell grafts provide successful
      neutrophil reconstitution. However, delayed platelet recovery, persistent
      decrease in CD4(+) lymphocyte levels and a high incidence of serious and life
      threatening late infections were observed in these children. There remains a
      critical need to evaluate any real clinical benefit of CD34(+) cell autografts in
      neuroblastoma patients.

PMID- 10881001
TI  - Improved outcome in childhood B-cell lymphoma with the intensified French LMB
      protocol.
AB  - BACKGROUND: During the last 20 years, 120 children with B cell lymphoma were
      treated at the National Pediatric Hematology/Oncology Center of Israel. Until
      1986, 63 patients received an institutional protocol (BMC), and thereafter 57
      patients received a modified French LMB protocol. We report the results of a
      retrospective analysis comparing the results of these two protocols. PROCEDURE:
      Patient characteristics were similar in both groups except for stage of disease
      and lactate dehydrogenase (LDH) levels. Significantly more patients in the LMB
      group had higher stage disease, and the LDH levels also were higher (<600
      microg/ml). RESULTS: Fifty-four of fifty-seven children on the modified LMB
      protocol are alive, disease-free, with an overall event-free survival of 94%
      (median follow-up of 73 months). Event-free survival for stages I, II, and III
      patients is 100%, and for stage IV 77%, whereas the overall event-free survival
      was 58% among 63 children treated previously, and for stage IV patients only 10%.
      Severe marrow suppression and neutropenic enterocolitis were the major
      complications of this intensive protocol. CONCLUSIONS: Intensive chemotherapy
      with a modified LMB protocol and modern supportive care result in a high cure
      rate of childhood B cell lymphoma even in patients with advanced disease.

PMID- 10881002
TI  - Low-dose daunorubicin in induction treatment of childhood acute lymphoblastic
      leukemia: no long-term cardiac damage in a randomized study of the Dutch
      Childhood Leukemia Study Group.
AB  - BACKGROUND: To investigate late cardiotoxicity in childhood acute lymphoblastic
      leukemia (ALL) survivors after induction treatment with or without daunorubicin
      (DNR; 25 mg/m(2), i.v., weekly, x4, cumulative dose 100 mg/m(2)). PROCEDURE:
      Cardiac function was assessed in 90 event-free survivors of childhood ALL, 11.4
      17.8 years (median 14.8 years) after treatment according to the DCLSG protocol
      ALL V. In this protocol patients were randomized to receive (group B) or not to
      receive (group A) DNR 25 mg/m(2)/week i.v. during the first 4 weeks of induction
      treatment. Age at diagnosis was 1.2-14.9 years (median 4.5 years). The cardiac
      evaluation consisted of a history, physical examination, electrocardiogram (ECG),
      24 hr ambulatory ECG, and echocardiography. RESULTS: Electrocardiographic data,
      arrhythmias, left ventricular dimensions, left ventricular contractility, wall
      stress, and diastolic function were within normal limits in both groups. No
      difference could be shown between data from group A (n = 40) and group B (n =
      50). CONCLUSIONS: No late cardiac damage was demonstrated in childhood ALL
      survivors after induction treatment including a cumulative dose of 100 mg/m(2)
      DNR, compared to survivors who received the same treatment but without DNR. DNR
      100 mg/m(2) given in 4 doses of 25 mg/m(2)/week appears to be a safe dose in
      induction treatment of ALL.

PMID- 10881003
TI  - Precursor B-cell lymphoblastic lymphoma in childhood and adolescence: clinical
      features, treatment, and results in trials NHL-BFM 86 and 90.
AB  - BACKGROUND: Precursor B-cell lymphoblastic lymphoma (PBLL) is a rare subtype of
      childhood non-Hodgkin lymphoma (NHL). The purpose of our study was to investigate
      frequency and clinicopathological features of PBLL in children and to test
      prospectively the efficacy of an ALL-type therapy for treatment of these
      patients. PROCEDURE: From October, 1986, to March, 1995, 1,075 patients up to 18
      years of age suffering from all kinds of NHL were registered in the two
      consecutive multicenter studies NHL-BFM 86 and 90. Of these, 27 patients were
      diagnosed with PBLL. Twenty-one PBLL patients were treated according to a BFM-ALL
      type protocol: an eight-drug induction over 9 weeks was followed by an 8-week
      consolidation including methotrexate 5 g/m(2) x4. Patients in stages I and II
      continued with maintenance up to a total therapy duration of 24 months, whereas
      patients in stages III and IV received an additional eight-drug intensification
      and cranial radiotherapy (12 Gy for prophylaxis) after consolidation. Six PBLL
      patients were treated according to the BFM-protocol for B-NHL, stratified
      according to stage and tumor load and consisiting of two to six 5-day courses of
      chemotherapy. RESULTS: The median age of the 27 patients with PBLL (18 boys, 9
      girls) was 6.2 (range 0.7-15) years. Stages (St. Jude) were: I (n = 3), II (n =
      7), III (n = 9), and IV (n = 8). Twenty-one PBLL patients had nodal disease, 6
      patients had subcutaneous manifestations, and 8 patients had bone marrow disease
      (<25% blasts). All patients achieved remission. With a median follow-up time of
      4. 25 years, the estimated probability for event-free survival (pEFS) at 10 years
      for the total group was 0.73 (SE 0.10). Five patients (2, 1, 1, and 1 patients at
      stages I, II, III, and IV, respectively) relapsed: 2 of 21 patients who were
      treated according to the ALL strategy and 3 of 6 who were treated according to
      the B-NHL-protocol. CONCLUSIONS: PBLL accounts for 2.5% of childhood NHL. An ALL
      type therapy strategy appears to be superior to a short-pulse B-NHL protocol.

PMID- 10881004
TI  - Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain following high
      dose methotrexate treatment for childhood cancer.
AB  - BACKGROUND: To avoid the late sequelae associated with cranial radiation therapy
      in childhood, intermediate- or high-dose intravenous methotrexate (HDMTX) has
      found increasing application as a means of preventing the development of overt
      central nervous system disease in childhood acute leukaemia. However, acute and
      chronic neurotoxicity has been described following HDMTX therapy, and the long
      term intellectual outcome in children treated in this way is inadequately
      documented. Proton magnetic resonance spectroscopy ((1)H-MRS) of the brain is a
      noninvasive, quantitative way of assessing aspects of cerebral metabolism, which
      has not previously been applied to the study of children undergoing central
      nervous system directed therapy. PROCEDURE: To evaluate the potential role of
      (1)H-MRS in the investigation of related neurotoxicity, 11 children who had
      received HDMTX (cumulative dose 6-96 g/m(2)) underwent localised (1)H-MRS,
      magnetic resonance imaging. Neuropsychological assessments were performed on the
      children who had more than 1 year of follow-up time since last methotrexate
      treatment. Control (1)H-MRS studies on 11 adult and 6 young volunteers were
      undertaken. Eight patients had spectra of adequate quality. Comparisons between
      (1)H-MRS metabolite ratios and normal controls were made. RESULTS: Patients had a
      low choline/water ratio compared to controls (P < 0.01). No differences between
      patient and control NAA/water, Cr/water, Naa/Cr, and Cho/Cr ratios were seen.
      Overall, 3 patients had abnormal white matter changes on MRI. The mean IQ of the
      patients (104.1) was in the normal range. CONCLUSIONS: It is postulated that
      choline depletion in the brains of these patients may reflect subclinical
      disturbances of myelin metabolism as a result of methotrexate therapy and may
      represent a possible avenue of treatment in patients with clinical chronic
      methotrexate-related neurotoxicity.

PMID- 10881005
TI  - Comparing thyroid ultrasonography to thyroid function in long-term survivors of
      childhood lymphoma.
AB  - BACKGROUND: We studied the value of thyroid ultrasonography as a follow-up tool
      in survivors of childhood lymphomas and correlated morphologic abnormalities with
      thyroid function tests. PROCEDURE: A prospective follow-up study of 45 long-term
      survivors of histology-proved childhood lymphomas was performed. Mean age at
      diagnosis was 9.1 years (range 2.1-16.4 years) and mean follow-up duration 10.9
      years (range 3.9-22.2 years). RESULTS: Among the 26 survivors of Hodgkin disease
      (HD) who received mantle field irradiation, 14 (54%) had abnormal ultrasonograms.
      Elevated thyroid-stimulating hormone (TSH) concentrations were found in 14 (54%),
      and 6 of them (42%) had normal thyroid functions. Six of twelve patients with
      normal ultrasonograms had abnormal thyroid function, and 5 of 11 patients with
      normal function had abnormal sonograms. Among the 19 non-HD survivors who did not
      receive radiotherapy, 18 (95%) had both normal sonograms and normal function.
      Thus thyroid gland abnormalities were detected in 54% of HD survivors after
      mantle field irradiation. No correlation between the abnormalities detected on
      ultrasonography and serum levels of TSH and thyroid hormones were found.
      CONCLUSIONS: Both ultrasound and thyroid function tests independently provide
      clinically useful information; the former examines gland morphologogy and the
      latter evaluates hormonal changes associated with thyroid disease. The high
      frequency of thyroid abnormalities detected by ultrasonography suggests that
      periodic thyroid ultrasonography is advisable in the follow-up of patients
      treated with mantle irradiation to screen for morphologic changes that may
      presage malignant transformation.

PMID- 10881006
TI  - Age is the major determinant of recurrence in pediatric differentiated thyroid
      carcinoma.
AB  - BACKGROUND: A relationship between young age and increased risk of recurrence of
      pediatric differentiated thyroid carcinoma has been suggested; however, no
      attempts have been made to assess the prognostic factors or efficacy of treatment
      in very young children with this malignancy. The objectives of this study were to
      evaluate the association of age with outcome in pediatric differentiated thyroid
      carcinoma and to compare the clinical, pathologic, prognostic, and treatment
      variables between younger and older children with this disease. PROCEDURE: A
      retrospective review of all patients presenting to the British Columbia's
      Children's Hospital or British Columbia Cancer Agency <17 years of age at
      diagnosis with differentiated thyroid carcinoma between January, 1955, and
      December, 1996, was completed. RESULTS: Thirty-eight patients were identified, 12
      of whom were </=10 years of age. The overall and relapse-free survivals at 20
      years were 100% and 32.2%, respectively. Age at diagnosis was the only
      determinant of time to recurrence on univariate and multivariate regression
      analysis of prognostic factors (P = 0.022). The 20 year relapse-free survival for
      children < or =10 years of age was 10.1% vs. 48.3% for children >10 years. An
      association between young age and extrathyroidal tumor invasion was identified (P
      = 0.016); however, the latter factor did not independently predict outcome. There
      was a trend for suppressive doses of thyroid hormone to improve outcome,
      particularly with increasing age at diagnosis, but this was not statistically
      significant. CONCLUSIONS: Age is the major determinant of recurrence in pediatric
      differentiated thyroid carcinoma. The results suggest different tumor biology in
      young children requiring novel approaches to therapy to decrease recurrence
      rates.

PMID- 10881007
TI  - Efficacy of immunization against hepatitis B virus infection in children with
      cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate the impact of hepatitis B
      prophylaxis in preventing hepatitis B infection in children with malignancy.
      PROCEDURE: Between May, 1993, and September, 1998, a total of 151 children (95
      boys, 56 girls), 29 (19%) with lymphoma, 58 (39%) with leukemia, and 64 (42%)
      with solid tumor, were screened for hepatitis B virus (HBV). The mean age was 7.
      5 +/- 2.5 years. Children with negative serology received active and/or passive
      immunization. HBsAg and anti-HBs were positive prior to vaccination in 16 (10%)
      and 17 (11%) children, respectively. One hundred eighteen children (78%) of one
      hundred fifty-one with negative serology were included in the vaccination
      program. The vaccine dose was 40 microg. Children with solid tumor and lymphoma
      received recombinant hepatitis B vaccine at diagnosis, repeated at months 1, 2,
      and 12. Hyperimmunglobulin was administered monthly in children with leukemia
      during the intensive chemotherapy period. They were then vaccinated following the
      third month of maintenance therapy with the schedule described above. Anti-HBs
      titers were measured every 3 months, and titers above 10 mlU/ml were accepted as
      protective. RESULTS: Anti-HBs positivity after the first three doses was 77% in
      solid tumors, 88% in acute leukemia, and 48% in lymphomas. Anti-HBs positivity
      with respect to diagnosis in children completing the vaccination schedule was 94%
      in solid tumor, 90% in leukemia, and 74% in lymphoma (P > 0.05). Thirty-three
      percent of children have not received the fourth dose as yet. In total 78% of the
      children developed protective antibody titers with or without the fourth dose,
      and none was infected with HBV during 3 years of follow-up. Ten (39%) of twenty
      six children who remained unresponsive to immunization were infected with HBV.
      CONCLUSIONS: These data reveal that HBV prophylaxis is necessary and that our
      vaccination schedule is effective in preventing HBV infection in these children.

PMID- 10881008
TI  - Gonadal and sexual function in men treated for childhood cancer.
AB  - BACKGROUND: Insofar as a majority of children with malignant diseases are cured,
      the late effects of treatment are of major importance. PROCEDURE: A retrospective
      study was conducted of gonadal and sexual function of 77 adult male survivors of
      childhood malignancies treated and cured at a single center from 1970 to 1989 and
      followed for a median of 13 years. The study included an interview, physical
      examination, sperm test, and hormonal analyses. RESULTS: One-third of the
      patients were treated for hematological malignancies, one-third for CNS tumors,
      and one-third for other malignancies. Eleven patients required androgen
      substitution after treatment for tumors of the pituitary-hypothalamic region or
      acute lymphoblastic leukemia including testicular irradiation and/or orchiectomy.
      In three patients the testicles were removed. The other eight had small
      testicles, and those providing sperm samples had azoospermia, and sexual function
      was disturbed in most of them. Most of the remaining 66 patients had small
      testicles. Normozoospermia was found in 63%, oligozoospermia in 20%, and
      azoospermia in 17%. Although there was a highly significant correlation between
      testicular volume and sperm test, 25% of patients with testicles of <10 ml had
      normozoospermia. Sexual function was normal in 46 patients, and they were married
      at a frequency comparable to the normal population. Twenty-one patients had no
      signs of gonadal dysfunction. CONCLUSIONS: Patients treated for tumors in the
      hypothalamic-pituitary region or treated with testicular irradiation or with high
      doses of alkylating agents had severe gonadal and sexual dysfunction. Most of the
      other patients had good prospects for preserved gonadal and sexual function.

PMID- 10881009
TI  - Silhouette: Maude Abbott, MD, "Madonna of the heart".

PMID- 10881010
TI  - Growth of a new intrarenal lesion in the remaining kidney of a patient with
      bilateral nephroblastomatosis and a previous nephrectomy for Wilms tumor.

PMID- 10881011
TI  - Clinical approach to renal lesions in children with multiple nephrogenic rests.

PMID- 10881012
TI  - Extraocular retinoblastoma.

PMID- 10881013
TI  - Radioresistant sensitization of neuroblastoma by cisplatin?

PMID- 10881014
TI  - No responses to oral etoposide in 15 patients with recurrent brain tumors.

PMID- 10881015
TI  - Pierre Robin syndrome and Wilms tumor: an unusual association.

PMID- 10881016
TI  - Synchronous occurrence of pleuropulmonary blastoma and cystic nephroma: possible
      genetic link in cystic lesions of the lung and the kidney.

PMID- 10881017
TI  - Adrenocortical carcinoma associated with adrenogenital syndrome in a child.

PMID- 10881018
TI  - LNCaP progression model of human prostate cancer: androgen-independence and
      osseous metastasis.
AB  - BACKGROUND: Clinically, the lethal phenotypes of human prostate cancer are
      characterized by their progression to androgen-independence and their propensity
      to form osseous metastases. We reported previously on the establishment of
      androgen-independent (AI) human prostate cancer cell lines derived from androgen
      dependent (AD) LNCaP cells, with androgen independence defined as the capability
      of prostate cancer cells to grow in castrated hosts. One of the sublines, C4-2,
      was found to be AI, highly tumorigenic, and metastatic, having a proclivity for
      metastasis to the bone. METHODS: We established the AI and bone metastatic cell
      sublines B2, B3, B4, and B5 from the parental C4-2 subline, using a previously
      established coinoculating procedure. We determined the biologic behavior of the
      parental and derivative LNCaP sublines in vivo and in vitro, as well as their
      molecular and cytogenetic characteristics. RESULTS: Unlike other human prostate
      cancer models, the LNCaP progression model shares remarkable similarities with
      human prostate cancer. We observed a comparable pattern of metastasis from the
      primary to the lymph node and to the axial skeleton, with a predominant phenotype
      of osteoblastic reaction; 25-37.5% of the animals developed paraplegia.
      Cytogenetic and biochemical characterizations of LNCaP sublines also indicate
      close similarities between human prostate cancer and the LNCaP progression model.
      Additional chromosomal changes were detected in B2-B5 sublines derived from C4-2
      bone metastases. These LNCaP sublines were found to grow faster under anchorage
      dependent but not -independent conditions. The in vitro invasion and in vivo
      metastatic potential of these LNCaP sublines surprisingly correlated with
      anchorage-dependent and not -independent growth. The derivative LNCaP sublines
      when cultured in vitro produced a substantially higher (20-30-fold) amount of
      basal steady-state concentrations of PSA than that of the parental LNCaP cells.
      PSA production was high initially, but was markedly reduced when the derivative
      cell lines were inoculated and allowed to grow long-term in vivo for the
      establishment of tumors and metastasis, suggesting that unknown host factors
      derived either from the prostate or the bone can effectively downregulate PSA
      expression by prostate tumor epithelium. CONCLUSIONS: The LNCaP model of human
      prostate cancer progression will help improve our understanding of the mechanisms
      of androgen-independence and osseous metastasis, and tumor-host determinants of
      PSA expression.

PMID- 10881019
TI  - Benign hyperplasia of the human prostate is associated with tissue enrichment in
      chondroitin sulphate of wide size distribution.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) involves qualitative and
      quantitative alterations in extracellular matrix (ECM) components affecting
      stromal-epithelial interactions. Glycosaminoglycans (GAGs) are polysaccharide
      components of the ECM whose role in the development of BPH is under
      investigation. METHODS: GAGs were extracted from human prostates of normal and
      BPH origin and were subsequently fractionated through DEAE-sephacel anion
      exchange chromatography. The isolated GAG fractions were identified through
      electrophoresis on cellulose acetate membranes and treatment with GAG-degrading
      enzymes of known specificity. Their size distribution was determined through
      gradient polyacrylamide gel electrophoresis. RESULTS: Isolated prostatic GAGs
      included hyaluronic acid (HA), heparan sulphate (HS), and a mixture of dermatan
      sulphate (DS) and chondroitin sulphate (CS). The CS/DS ratio was significantly
      higher in hyperplastic as compared to normal prostates. A difference was also
      observed with respect to the apparent molecular mass of the DS-CS mixture, which
      reflects the CS enrichment in BPH. GAGs isolated from hyperplastic prostates were
      more diverse in size as compared to the corresponding glycans from normal
      prostates. CONCLUSIONS: The apparent increase in CS and decrease in DS content in
      prostates of patients with BPH is in good agreement with the pathological
      manifestation of increased cell proliferation in hyperplastic prostate tissue,
      since these glycan molecules have been reported to increase and decrease cell
      proliferation, respectively. Identification of the responsible enzymes involved
      in the homeostasis of CS and DS may provide alternative targets for
      pharmacological intervention.

PMID- 10881020
TI  - Modulating effect of estrogen and testosterone on prostatic stromal cell
      phenotype differentiation induced by noradrenaline and doxazosin.
AB  - BACKGROUND: Noradrenaline (NA) has been shown to enhance expression of the
      contractile phenotype of human prostatic stromal cells in tissue culture. This
      study examined the possibility that changing levels of sex hormones in elderly
      men with BPH may modulate the differentiating effect of NA and hence the efficacy
      of alpha(1)-adrenoceptor-blocking drugs. METHODS: Confluent, quiescent stromal
      cell cultures from 6 different patients were treated with combinations of 20
      microM NA, 1 microM doxazosin, 0.1 microM beta-estradiol, and 0.1 microM
      testosterone, over a period of 10 days. Harvested cells were labelled with
      fluorescein-conjugated antisera to alpha-smooth muscle actin and myosin to
      identify cells of contractile phenotype which were thereafter analyzed flow
      cytometrically. RESULTS: NA increased mean immunoexpression of both actin and
      myosin. Enhancement of myosin expression was highly significant (P </= 0.02).
      This effect was incompletely opposed by doxazosin. Neither estradiol nor
      testosterone influenced mean expression of contractile filaments and did not
      significantly enhance or inhibit the effects of NA or doxazosin. However, both
      sex hormones exhibited a differentially powerful effect on cell lines from
      individual patients. The expression of myosin increased by NA was further
      elevated by addition of estradiol in four of the cell lines and by testosterone
      in three. CONCLUSIONS: The data suggest that levels of estrogens and androgens,
      either alone or in combination, are unlikely to predict the development of
      obstructive symptoms in patients with BPH or their response to doxazosin.
      Nevertheless, prostatic stromal cells from individual patients may be
      exceptionally sensitive to both sex hormones, with enhanced modulation towards a
      contractile phenotype. Since alpha- and beta-subtypes of the estrogen receptor
      are differentially expressed between the stroma and epithelium of the early fetal
      prostate, it is likely that interaction between sex hormones and noradrenaline is
      an important factor in determining the phenotypic composition of prostatic stroma
      at this early stage of development, and possibly predisposition to BPH during
      later adult life.

PMID- 10881021
TI  - Decreased galectin-3 expression in prostate cancer.
AB  - BACKGROUND: Galectin-3 is a carbohydrate-binding protein whose level of
      expression has been shown to be correlated with metastatic potential in a number
      of different tumor types. The purpose of this investigation was to examine
      galectin-3 expression in several tumorigenic and nontumorigenic prostate cell
      lines and prostate tissue samples. METHODS: The expression of galectin-3 in cell
      lines and tissue samples was evaluated by tissue immunohistochemistry and Western
      blot analysis. RESULTS: Human cell lines PC-3M, PC-3, DU-145, PrEC-1, and MCF10A
      demonstrated the presence of galectin-3. Galectin-3 was not detected in TSU-pr1
      and LNCaP by Western blot analysis. We furthered our studies by examining a
      series of human prostate tissue samples for expression of galectin-3. Overall,
      approximately 60-70% of the normal tissue examined demonstrated heterogenous
      expression of galectin-3. In stage II tumors, however, there was a dramatic
      decrease in galectin-3 expression in both PIN and tumor sections, with only 10.5%
      (2/19) of these samples expressing this protein. Stage III tumors also
      demonstrated a decreased expression of galectin-3, although this downregulation
      was not as dramatic, with 35% of PIN samples and 52% of tumor tissue expressing
      galectin-3 (P < 0.01). CONCLUSIONS: These data demonstrate that galectin-3 is
      downregulated in prostate cancer. The altered downregulation pattern of galectin
      3 observed between tumor stages suggests different roles for galectin-3 in the
      progression of prostate cancer.

PMID- 10881022
TI  - Autocrine effect of DHT on FGF signaling and cell proliferation in LNCaP cells:
      role of heparin/heparan-degrading enzymes.
AB  - BACKGROUND: LNCaP cells are androgen-sensitive human prostate cancer cells. They
      are characterized by a bell-shaped growth curve in response to increasing doses
      of dihydrotestosterone (DHT) in culture. At a low concentration of DHT (0.1 nM),
      these cells show an increase in proliferation, but their growth is arrested at a
      high concentration (100 nM) of DHT. Results of our previous study demonstrated
      that the inhibitory effect of DHT at a high concentration was mediated through
      the action of TGF-beta1. The objective of the present study was to elucidate the
      mechanism of the proliferative effect of DHT in LNCaP cells. METHODS AND RESULTS
      DHT stimulated LNCaP proliferation only when cells were cultured in the presence
      of serum. In serum-free cultures, the characteristic DHT-induced proliferation
      was not observed. The addition of neutralizing antibody against FGF-2 (basic
      fibroblast growth factor) was able to inhibit this DHT-induced proliferation.
      These results suggest that the proliferative effect of DHT was mediated through
      the action of FGF-2. However, results of the reverse transcriptase polymerase
      chain reaction indicated that LNCaP cells did not express FGF-2 message. As a
      result, the source of FGF-2 in these cultures must be the serum supplemented in
      the culture media. FGF-2 can bind to heparin sulfate chains within the
      extracellular matrix (ECM). In cultures treated with exogenous heparin, the
      proliferative effect of DHT was abolished. These results led to the development
      of the hypothesis that DHT treatment mediates the release of FGF-2 entrapped in
      the ECM through increased heparinase activity. The addition of heparinase to
      cultures of LNCaP cells, in the absence of DHT, was able to stimulate cell
      proliferation. Moreover, 0.1 nM DHT caused a significant increase in heparinase
      activity. CONCLUSIONS: These results provide a possible mechanism for DHT action
      in LNCaP cells. In the absence of DHT, FGF-2 in culture was trapped in the
      extracellular matrix and was not available to interact with LNCaP cells. However,
      in the presence of 0.1 nM DHT, heparinase activity in the culture was elevated
      and, as a result, it liberated the trapped FGF-2 which, in turn, stimulated
      proliferation in LNCaP cells.

PMID- 10881023
TI  - Metastatic burden in nude mice organs measured using prostate tumor PC-3 cells
      expressing the luciferase gene as a quantifiable tumor cell marker.
AB  - BACKGROUND: Sensitive procedures for quantitative measurement of tumor cell
      spread as a function of time and primary tumor size are necessary to generate
      models of metastasis and formulate therapies. METHODS: Prostate carcinoma cells
      PC-3.luc expressing the luciferase gene were intramuscularly inoculated in nude
      mice to generate experimental tumors. Metastatic cells in target organs were
      easily counted by their capacity to produce light. RESULTS: Tumor cells were very
      mobile and migrated to all the target organs examined: lymph nodes, brain, bone,
      lungs, liver, kidney, spleen, testicles, prostate, seminal vesicle, and scrotum.
      Organ colonization started very early, 14 days after inoculation, when primary
      tumors were very small and produced an amount of light equivalent to that
      generated by 2 x 10(4) tumor cells in vitro (tumor cell equivalents, TCEs). Tumor
      cell burden could be quantitatively described by power functions of time or
      primary tumor light-producing capacity. The ratio of metastatic TCEs to primary
      tumor TCEs clustered around organ characteristic values: 10(-3) for femur and
      lumbar lymph nodes, 10(-6) for the spleen, and 10(-3) for the added set of
      organs. CONCLUSIONS: Dispersal of PC-3 tumor cells from IM experimental tumors
      started early before the third week postinoculation and when primary tumors had 2
      x 10(4) TCEs. Tumor cells were found widely spread in all the organs tested. The
      possibility of easily quantifying tumor cell burden should make this approach
      useful for the study of metastasis and the development of antimetastatic
      therapies.

PMID- 10881024
TI  - Localization of antioxidant enzymes and oxidative damage products in normal and
      malignant prostate epithelium.
AB  - BACKGROUND: The risk for prostate cancer seems to be reduced by certain
      antioxidant compounds (vitamins E and A, and selenium). METHODS: Antioxidant
      enzymes and oxidative damage products were localized in normal prostatic
      epithelium and malignant glands in primary and metastatic prostatic
      adenocarcinomas, using well-characterized antibodies and immunoperoxidase
      techniques. RESULTS: Antioxidant enzymes and four markers of oxidative damage
      were compared in basal and secretory cells of normal prostatic epithelium and
      prostate adenocarcinoma cells, and each cell type had unique patterns of enzymes
      and oxidative damage products. One marker of oxidative damage, a fluorophore
      derived from 4-hydroxy-2-nonenal-lysine adduction, was found in secretory cells
      of normal but not malignant epithelium, demonstrating a different oxidative
      metabolism in normal vs. malignant prostate epithelium. Metastatic lesions from
      primary prostate cancer had higher levels of manganese superoxide dismutase and
      nuclear oxidative damage products than did primary tumors. CONCLUSIONS:
      Antioxidant enzymes and oxidative damage products are modulated in metastatic
      compared to primary prostate cancer.

PMID- 10881025
TI  - Polymeric micellar paclitaxel phosphorylates Bcl-2 and induces apoptotic
      regression of androgen-independent LNCaP prostate tumors.
AB  - BACKGROUND: Paclitaxel has been difficult to evaluate in preclinical tumor model
      systems because its poor solubility requires a Cremophor EL formulation, which
      results in lethal anaphylaxis. We tested the effectiveness of a novel polymeric
      micellar paclitaxel on androgen-independent tumor growth in the LNCaP tumor
      model. METHODS: Athymic male mice bearing LNCaP tumors were castrated and allowed
      to grow until their PSA levels increased to three times above precastration
      levels. The animals were then treated with 0.5 mg intravenous polymeric micellar
      paclitaxel once daily for the first 5 days of a 3-week cycle. In total, three
      cycles were given. Tumor volume and serum PSA levels were measured weekly to
      monitor tumor progression. RESULTS: In vitro mitogenic assays demonstrated that
      polymeric micellar paclitaxel was effective in inhibiting LNCaP cell growth with
      an IC(50) of 5 nM. Paclitaxel precipitated apoptosis in vitro at a concentration
      of 1 nm and higher, confirmed by DNA laddering. Western blotting demonstrated
      that paclitaxel treatment phosphorylated and inactivated Bcl-2. In mice bearing
      LNCaP tumors treated with micellar paclitaxel, tumors regressed rapidly with the
      commencement of micellar paclitaxel treatment. Tumor size decreased 91% and PSA
      level decreased 96% after three cycles of treatment. TUNEL immunostaining of the
      tumor treated with micellar paclitaxel showed marked apoptosis when compared with
      the control. No significant side effects or mortality was observed in the
      micellar paclitaxel group (n = 7). In contrast, all (n = 7) mice treated with
      conventional Cremophor EL paclitaxel died within 1 day of injection. CONCLUSIONS:
      The polymeric micellar paclitaxel formulation is water-soluble and capable of
      inducing complete response in mice bearing androgen-independent LNCaP tumors. The
      lack of toxicity of polymeric micellar paclitaxel permits in vivo preclinical
      testing of paclitaxel-based combination regimens.

PMID- 10881026
TI  - Phenotypic characterization of immortalized normal and primary tumor-derived
      human prostate epithelial cell cultures.
AB  - BACKGROUND: Cell lines can provide powerful model systems for the study of human
      tumorigenesis. However, the human prostate cancer cell lines studied most
      intensively by investigators (PC3, DU145, and LNCaP) were established from
      metastatic lesions, and it is unlikely that they accurately recapitulate the
      genetic composition or biological behavior of primary prostate tumors. Cell lines
      more appropriate for the study of human prostate primary tumors would be those
      derived from spontaneously immortalized cells; unfortunately, explanted prostate
      cells survive only short-term in culture, and rarely immortalize spontaneously.
      Therefore, we examined whether cell lines developed through viral gene-mediated
      immortalization of human normal or primary tumor prostate epithelium express
      aspects of the normal or malignant phenotypes, and could serve as appropriate
      models for normal or transformed human prostatic epithelium. METHODS: To
      accomplish these goals, we assessed the phenotypic expression of cell cultures
      established through the immortalization of normal (1532N, 1535N, 1542N, and PrEC
      T) or malignant (1532T, 1535T, and 1542T) human prostate epithelium with the E6
      and E7 genes of HPV-16, or the large T antigen gene of SV40. RESULTS: Examination
      of these cell lines for their proliferative rates and their abilities to grow
      with or without serum or androgen stimulation, to form colonies in soft agar, or
      to form tumors in vivo, suggests that they may serve as valid, useful tools for
      the elucidation of prostate tumorigenesis. Moreover, the observation of
      structural alterations involving chromosome 8, including gain of 8q in 3 of the 4
      cell lines expressing aspects of the malignant phenotype, implies that these cell
      lines accurately recapitulate the genetic composition of primary prostate tumors.
      CONCLUSIONS: Taken together, these data suggest that cell lines generated from
      immortalized normal or primary tumor epithelium may be useful for the elucidation
      of early transforming events in the prostate.

PMID- 10881027
TI  - Potentiation of the inhibitory effect of growth hormone-releasing hormone
      antagonists on PC-3 human prostate cancer by bombesin antagonists indicative of
      interference with both IGF and EGF pathways.
AB  - BACKGROUND: In view of the involvement of various neuropeptides and growth
      factors in the progression of androgen-independent prostate cancer, we
      investigated the effects of antagonists of growth hormone-releasing hormone
      (GHRH) alone or in combination with an antagonist of bombesin/gastrin-releasing
      peptide (BN/GRP) on PC-3 human prostate cancers. METHODS: Nude mice implanted
      with PC-3 tumors received GHRH antagonists MZ-5-156 or JV-1-38, each at 20
      microgram/day s.c. In experiment 2, treatment consisted of daily injections of JV
      1-38 (20 microgram), BN/GRP antagonist RC-3940-II (10 microgram), or a
      combination of JV-1-38 and RC-3940-II. Serum IGF-I levels, expression of mRNA for
      IGF-II, and characteristics of BN/GRP and EGF receptors in tumor tissue were
      investigated. RESULTS: JV-1-38 induced a greater inhibition of tumor growth and
      suppression of IGF-II mRNA than MZ-5-156, both compounds causing a similar
      decrease in serum IGF-I. In experiment 2, JV-1-38 and RC-3940-II produced a
      comparable reduction in tumor volume (65% and 61%, respectively), but a
      combination of both antagonists augmented tumor inhibition to 75%. Combined
      treatment with JV-1-38 and RC-3940-II also led to a greater suppression of IGF-II
      mRNA (92%), as compared with JV-1-38 (72%) or RC-3940-II (77%). Serum IGF-I
      concentration was lowered only in mice treated with JV-1-38, while the
      downregulation of BN/GRP and EGF receptors was specific for groups receiving RC
      3940-II. CONCLUSIONS: The inhibitory effects of GHRH antagonists on PC-3 human
      androgen-independent prostate cancer can be potentiated by concomitant use of
      BN/GRP antagonists. The combination of both types of analogs apparently
      interferes with both IGF and bombesin/EGF pathways, and might be clinically
      useful for the management of androgen-independent prostate cancer.

PMID- 10881028
TI  - Effect of partial volume correction on estimates of the influx and cerebral
      metabolism of 6-[(18)F]fluoro-L-dopa studied with PET in normal control and
      Parkinson's disease subjects.
AB  - The poor spatial resolution of positron emission tomography (PET) is a limiting
      factor in the accurate assay of physiological processes investigated by
      compartmental modeling of tracer uptake and metabolism in living human brain. The
      radioactivity concentration in a region-of-interest is consequently altered by
      loss of signal from that structure and contamination from adjacent brain regions,
      phenomena known as partial volume effects. We now apply an MRI-based algorithm to
      compensate for partial volume effects in the special case of compartmental
      modeling of the cerebral uptake of 6-[(18)F]fluoro-L-dopa (FDOPA), an exogenous
      substrate of dopa decarboxylase. High-resolution MRI scans were obtained from
      normal volunteers (n = 4) and patients with Parkinson's disease (n = 4) in order
      to segment specific brain regions and calculate the partial volume correction
      factors. Dynamic 2D PET scans were acquired during 90 min following intravenous
      infusion of FDOPA. After partial volume correction, the apparent net blood-brain
      clearance of FDOPA (K(i)) was greatly increased in caudate and putamen of normal
      subjects and in caudate of Parkinson's disease patients. The equilibrium
      distribution volume of FDOPA (V(D)(e)) in cerebral cortex increased by 35% in all
      subjects. Using a two-compartment model, the relative activity of dopa
      decarboxylase with respect to FDOPA (k(D)(3)) in the basal ganglia was increased
      2-3 times in normal subjects, to the range obtained previously in brain of living
      rat. The partial volume correction also increased the magnitude of k(D)(3) in
      caudate of Parkinson's disease patients, but did not alter k(D)(3) in putamen. A
      three-compartment model correcting for elimination of decarboxylated metabolites
      also yielded higher estimates of k(D)(3), but with a penalty in precision of the
      estimates. Together, these observations suggest that the limited spatial
      resolution of PET results in substantial underestimation of the true rate of
      FDOPA uptake and metabolism in vivo, and may also tend to obscure regional
      heterogeneity in the neurochemical pathology of Parkinson's disease.

PMID- 10881029
TI  - Docosahexaenoic acid inhibits synaptic transmission and epileptiform activity in
      the rat hippocampus.
AB  - Docosahexaenoic acid (DHA) has been suggested to be required for neuronal
      development and synaptic plasticity. However, in view of the fact that DHA
      facilitates NMDA responses and blocks K(+) channels, it might predispose the
      neurons to epileptiform bursting. By using extracellular recording of population
      spikes in the CA1 region of rat hippocampal slices, we tested this possibility by
      examining the effect of DHA on the epileptiform activity induced by bicuculline
      or in Mg(2+)-free medium. When stimuli were delivered to the Schaffer
      collateral/commissural pathway every 20 or 30 sec, DHA had no significant effect
      on the epileptiform activity. However, when the frequency of stimulation was
      increased to 0.2 Hz, DHA attenuated the amplitude of the bursting activity
      induced by bicuculline to 57.5+/- 10.8% and those induced by Mg(2+)-free ACSF to
      65.8+/-13.9% of control. DHA reduced the slope of field excitatory postsynaptic
      potential (fEPSP) to 77.1+/-7.4% of baseline, without significant effect on the
      ratio of paired-pulse facilitation (PPF). By intracellular recording of neurons
      in the stratum pyramidale of rat hippocampal slices, we found that DHA markedly
      inhibited the repetitive firing of action potentials elicited by depolarizing
      current pulses but did not affect the initial action potential. Thus, DHA may
      attenuate epileptic activity mainly through the frequency-dependent blockade of
      Na(+) channels.

PMID- 10881030
TI  - Ketamine decreased striatal [(11)C]raclopride binding with no alterations in
      static dopamine concentrations in the striatal extracellular fluid in the monkey
      brain: multiparametric PET studies combined with microdialysis analysis.
AB  - The effects of ketamine, a noncompetitive antagonist of NMDA receptors, on the
      striatal dopaminergic system were evaluated multiparametrically in the monkey
      brain using high-resolution positron emission tomography (PET) in combination
      with microdialysis. L-[beta-(11)C]DOPA, [(11)C]raclopride, and [(11)C]beta-CFT
      were used to evaluate dopamine synthesis rate, D(2) receptor binding, and
      transporter availability, respectively, in conscious and ketamine-anesthetized
      animals. Dopamine concentrations in the striatal extracellular fluid (ECF) were
      simultaneously measured by PET. Thirty minutes prior to PET scan, intravenous
      administration of ketamine was started by continuous infusion at a rate of 3 or
      10 mg/kg/h. Ketamine infusion dose-dependently decreased [(11)C]raclopride
      binding, but induced no significant changes in dopamine concentration in the
      striatal ECF as measured by microdialysis at any dose used. In contrast, ketamine
      increased both dopamine synthesis and DAT availability as measured by L-[beta
      (11)C]DOPA and [(11)C]beta-CFT, respectively, in a dose-dependent manner. These
      results suggest that the inhibition of glutamatergic neuronal activity modulates
      dopamine turnover in the striatum by simultaneous enhancement of the dynamics of
      dopamine synthesis and DAT availability to the same extent, resulting in no
      apparent changes in ECF dopamine concentration as measured by microdialysis. It
      also suggests that the alteration of [(11)C]raclopride binding in vivo as
      measured by PET might not simply be modulated by the static synaptic
      concentration of dopamine.

PMID- 10881031
TI  - Nicotine-induced excitation of locus coeruleus neurons is blocked by elevated
      levels of endogenous kynurenic acid.
AB  - The present electrophysiological study shows that manipulation with endogenous
      brain kynurenic acid (KYNA) is able to affect the response of central
      noradrenergic neurons to nicotine. Previous studies have shown that systemically
      administered nicotine in low doses is associated with a marked, but short-lasting
      increase in the firing rate of rat noradrenergic neurons in the locus coeruleus
      (LC). This action of nicotine is of peripheral origin and finally mediated via a
      release of glutamate within the LC. KYNA is an endogenous glutamate receptor
      antagonist, which shows an uneven distribution in human brain. Previous studies
      have shown that a potent inhibitor of kynurenine 3-hydroxylase, PNU 156561A, is
      able to dose-dependently increase the levels of KYNA in brain. Anesthetized rats
      were given PNU 156561A in a dose that caused a 5-fold increase in brain KYNA
      levels after 3-6 hours (40 mg/kg, i.v. ). This treatment was found to abolish the
      increase in firing rate of LC neurons induced by nicotine (25-200 microg/kg,
      i.v.). The results of the present study show that an increased concentration of
      endogenous brain KYNA is able to inhibit the activation of central noradrenergic
      neurons by nicotine. In addition, our results highlight the role of endogenous
      KYNA in brain as a potentially important modulator of brain glutamatergic
      responses.

PMID- 10881032
TI  - Fluorine-18-labeled tropane analogs for PET imaging studies of the dopamine
      transporter.
AB  - A series of PET imaging studies were conducted with two fluorine-18-labeled
      tropane analoges, [(18)F](+)-FTT and [(18)F](+)-FCT. Both compounds possessed a
      high affinity and selectivity for the dopamine transporter and had a higher
      accumulation in the basal ganglia, a brain region having a high density of the
      dopamine transporter (DAT) than the cerebellum, a reference region devoid of
      dopaminergic terminals. [(18)F](+)-FCT had a higher brain uptake and more
      suitable basal ganglia:cerebellum (BG:Cb) ratio than [(18)F](+)-FTT. [(18)F](+)
      FCT also displayed reversible binding kinetics in vivo, indicating that the
      measurement of DAT density in vivo with PET will be relatively insensitive to
      changes in cerebral blood flow that can occur as a consequence of disease or
      prolonged cocaine abuse. The uptake of [(18)F](+)-FCT was also displaced by an
      intravenous injection of cocaine (1.0 mg/kg), which is consistent with the
      labeling of the DAT in vivo by this radiotracer. These data suggest that
      [(18)F](+)-FCT may be a suitable radiotracer for studying DAT function in vivo
      with PET.

PMID- 10881033
TI  - In vivo regulation of mu-opioid receptor density and gene expression in CXBK and
      outbred Swiss Webster mice.
AB  - Chronic in vivo treatment with the opioid agonist etorphine downregulates mu
      opioid receptor density, produces tolerance, and regulates gene expression in the
      mouse. After cessation of treatment, there is an increase in mu-opioid receptor
      mRNA level associated with the recovery of mu-opioid receptors. However, the
      effect of etorphine on the regulation of mRNA during treatment is currently not
      known. In this study, etorphine-induced changes in mu-opioid receptor density,
      mRNA, and opioid analgesic potency were determined in two mouse strains that
      differ in basal mu-opioid receptor density in brain. CXBK mice (mu-opioid
      receptor deficient) and outbred Swiss Webster mice were implanted s.c. with
      placebo pellets (controls) or etorphine minipumps (250 microg/kg/day) for 1-7
      days and mu-opioid receptor density or mRNA levels in whole brain were assessed
      or mice were tested for etorphine analgesia following 7 days of treatment. In
      control CXBK mice, mu-receptor density was approximately 40% less than that for
      the Swiss Webster, although mRNA abundance was similar in both strains.
      Etorphine's potency was 4-fold greater in control Swiss Webster compared to CXBK
      mice. Etorphine treatment decreased ( approximately 25-40%) mu-receptor density
      similarly in both strains throughout treatment. The magnitude of analgesic
      tolerance to etorphine was 8-fold in both mouse strains. Etorphine produced a
      biphasic effect on receptor mRNA in both strains with levels decreased (25%) by 3
      days and increased (30-40%) at 7 days. mRNA levels remained elevated (55%) 16 h
      following the end of the 7 day etorphine treatment. Taken together, these data
      suggest that in vivo etorphine treatment that produces mu-opioid receptor
      downregulation and tolerance, can regulate mu-opioid receptor mRNA abundance.
      Receptor downregulation may initially induce decreases in mRNA levels since
      downregulation preceded a decrease in gene expression. Prolonged (>3 days)
      receptor downregulation may be responsible for increasing message levels and may
      be important in recovery of receptors following treatment. In addition, the
      magnitude of changes in receptor density, mRNA, and tolerance were similar in
      both CXBK and Swiss Webster mice, indicating that the mechanisms required for
      receptor regulation and its functional consequences are independent of basal mu
      opioid receptor density.

PMID- 10881034
TI  - Dopamine D(5) receptor immunolocalization in rat and monkey brain.
AB  - Dopamine D(5) receptor localization has been difficult because even the most
      specific ligands cannot distinguish between molecular subtypes of the D(1)-like
      receptor subfamily. Antifusion protein rabbit polyclonal antibodies directed
      against the C-terminus of human D(5) receptor were therefore developed for
      immunolocalization of the D(5) receptor protein in brain. The antibodies were
      characterized by immunoblot analysis and immunoprecipitation and used for light
      microscopic immunocytochemistry in rat and monkey brain. Affinity purified D(5)
      antibodies were specific for D(5) fusion protein as well as cloned and native
      D(5) receptor on Western blots, and D(5) antisera specifically immunoprecipitated
      solubilized, cloned D(5) receptor. Regional distribution of D(5) receptor
      immunoreactivity was consistent across species and correlated well with D(5) mRNA
      distribution previously reported in monkey brain. Immunoreactivity was widespread
      and tended to label perikarya and proximal dendrites of neurons in cerebral
      cortex, basal ganglia, basal forebrain, hippocampus, diencephalon, brainstem, and
      cerebellum. Neuropil was immunoreactive in olfactory bulb, islands of Calleja,
      cerebral cortex, superior colliculus, and molecular layer of cerebellum. The
      distribution of D(5) in brain was clearly different from that of other dopamine
      receptor subtypes, including D(1), the other member of the D(1)-like receptor
      subfamily. This unique distribution corroborates the idea that the D(5) receptor
      subtype has a distinct role in dopamine neurotransmission.

PMID- 10881035
TI  - Morphine-associated environmental cues elicit conditioned gene expression.
AB  - Drug-associated contextual cues can exert a powerful influence on behavior
      through associative pairing between the drug and the environment. However, the
      anatomical and molecular substrates for these effects are not well characterized.
      Using a drug-conditioning paradigm, we examined the expression of the immediate
      early gene product, Fos, within specific brain circuits using immunocytochemical
      detection. Rats were given either morphine (5 mg/ml/kg) or saline once a day for
      10 days. The drug administration was always paired with a specific environment
      (activity monitors) different from the home cage. Following this treatment, the
      rats were returned to the cages at various times thereafter, with only a mock
      injection. Conditioned behavioral activation was observed in rats at 3, 5, and 7
      days following treatment with morphine. In rats showing the conditioned motor
      response, several cortical and limbic areas showed substantial increases in the
      number of Fos positive cells, indicating that these regions were more active
      during exposure to the drug-paired environment. Areas that were most activated
      included prefrontal cortex, cingulate cortex, nucleus accumbens, and preoptic
      area. Further analysis showed that this increase in Fos expression was not
      directly related to the increase in motor activity, and that the drug-associated
      conditioning and Fos expression was lessened at 7 days and absent by 14 days post
      treatment. These results are discussed in terms of their relevance to the problem
      of relapse in drug addiction.

PMID- 10881036
TI  - Olfactory bulbectomy alters NMDA receptor levels in the rat prefrontal cortex.
AB  - Olfactory bulbectomized (OBX) rats show a variety of behavioral and biochemical
      deficits that parallel human depression. We investigated the expression of
      glutamate receptor subtypes in cortical and subcortical brain regions following
      bilateral olfactory bulbectomy in adult rats. Quantitative receptor
      autoradiography using [(125)I]MK-801 (NMDA receptor), [(3)H]AMPA (AMPA receptor),
      and [(3)H]kainate (kainate receptor) was performed on brain sections at 1-5 weeks
      following olfactory bulbectomy. Our results show an elevation of NMDA receptors
      in the medial prefrontal cortex within 1 week following bulbectomy, which
      persisted up to at least 5 weeks post-bulbectomy. Neither kainate nor AMPA
      receptors were altered in any brain region examined. The potential significance
      of these results is discussed in light of experimental findings supporting a role
      for NMDA receptors in the mechanism of action of antidepressant drugs and the
      pathophysiology of major depression.

PMID- 10881037
TI  - Neuroadaptations in dentate gyrus function following repeated methamphetamine
      administration.

PMID- 10881038
TI  - Dopamine receptor pruning in prefrontal cortex during the periadolescent period
      in rats.

PMID- 10881039
TI  - Dopamine transporter function assessed by antisense knockdown in the rat:
      protection from dopamine neurotoxicity.
AB  - The plasma membrane dopamine transporter is located on presynaptic nerve
      terminals and is responsible for the termination of dopaminergic
      neurotransmission via dopamine reuptake. The dopamine transporter may also
      contribute to the pathogenesis of Parkinson disease. Dopamine transporter
      expression correlates well with susceptibility to neuronal degeneration in 1
      methyl-4-phenyl-1,2,3,6 -tetrahydropyridine (MPTP)-induced parkinsonism. Recent
      studies have implicated the dopamine transporter in the uptake of both this
      neurotoxin and its metabolite, MPP(+), as well as another experimental
      neurotoxin, 6-hydroxydopamine. In these studies we examined the role of the
      dopamine transporter in the neurotoxicity of both MPP(+) and 6-hydroxydopamine in
      the rat brain using in vivo administration of phosphorothioate antisense
      oligonucleotides targeting dopamine transporter mRNA. Infusion of dopamine
      transporter antisense (1 nmol/day, 7 days) into the left substantia nigra pars
      compacta resulted in reduced (3)H-WIN 35-428 binding in the left striatum and
      significant levodopa and amphetamine-induced contralateral rotations. Unilateral
      pretreatment with dopamine transporter antisense prior to bilateral intrastriatal
      infusion of either MPP(+) or 6-hydroxydopamine resulted in asymmetrical striatal
      (3)H-WIN 35-428 binding and dopamine content as well as significant apomorphine
      induced ipsilateral rotations, suggesting neuroprotection of nigrostriatal
      neurons on the antisense-treated side. Thus, the dopamine transporter appears to
      play a critical role in determining susceptibility to the experimental
      neurotoxins MPP(+) and 6-hydroxydopamine. In light of this, the dopamine
      transporter may prove useful, both as a marker for susceptibility to Parkinson's
      disease and as a target for therapeutic intervention.

PMID- 10881040
TI  - Central serotonin system in Dystonia musculorum mutant mice: biochemical,
      autoradiographic and immunocytochemical data.
AB  - The autosomal recessive mutation dystonia musculorum (dt(J)/dt(J)) causes
      degenerative alterations of peripheral and central sensory pathways that lead to
      ataxia. To investigate possible changes in the central serotonin system of these
      mice, HPLC measurements of 5-hydroxytryptophan, 5-hydroxy-tryptamine (serotonin;
      5-HT), and 5-HT metabolites were obtained from 22 brain regions and the spinal
      cord of wild type and dt(J)/dt(J) mutant mice. Also, 5-HT transporters were
      quantified by [(3)H]citalopram autoradiography in 72 brain regions, subregions,
      and nuclei, and the 5-HT innervation visualized by immunocytochemistry throughout
      the brain and spinal cord. In all brain regions measured for indoleamine content,
      there were no significant differences between the two genotypes. In the spinal
      cord, an increased tissue concentration of 5-HT (+34%), 5-hydroxyindole-3-acetic
      acid (+33%), 5-hydroxytryptophol (+21%), and 5-hydroxytryptophan (+45%) in
      dt(J)/dt(J) actually corresponded to the same total amount of each of these
      indoleamines in the entire spinal cord, when taking into account its reduced size
      in the mutants. Quantification of the binding to 5-HT transporters showed
      increases in the medial geniculate nucleus (+14%), medial (+24%) and lateral
      (+18%) hypothalamus, interpeduncular (+13%), vestibular (+22%), and deep
      cerebellar nuclei (+37%) of dt(J)/dt mice, and decreases in the ventral tegmental
      area (-13%), median and linear raphe nuclei (-20%), as well as in the solitary
      complex (-35%). There were no apparent differences in the distribution of 5-HT
      immunostained fibers in these and other regions of brain and in the spinal cord
      of dt(J)/dt(J) compared to wild type mice. The bulk of these results indicates a
      relative sparing of the central 5-HT system in the dt(J)/dt(J) mice, even though
      alterations in 5-HT transporters could justify attempts at improving the
      sensorimotor dysfunction by administration of serotoninergic agents in these
      mice.

PMID- 10881042
TI  - Super-stereotypy II: enhancement of a complex movement sequence by
      intraventricular dopamine D1 agonists.
AB  - This study compared the effect of intraventricular administration of dopamine D1
      or D2 agonists or of ACTH on the sequential stereotypy of a serial pattern of
      grooming movements ("syntactic chain"). In a previous study, we showed that
      peripheral administration of D1 agonists increased the probability of occurrence
      and enhanced the stereotypy of the already-stereotyped movement pattern. Here we
      made microinjections of either SKF 38393 (a partial D1 agonist; 5, 10, 15, 20, 40
      microg), SKF 82958 (a full D1 agonist; 5, 10, 20 microg), quinpirole (a D2
      agonist; 5, 10, 20 microg), or ACTH-(1-24) (2, 5, 10 microg) into the lateral
      ventricles of rats. We measured the amount of grooming, the relative probability
      that the complex sequence pattern would occur, and the degree to which the
      syntactic pattern was completed faithfully. The total amount of grooming behavior
      was increased by intraventricular SKF 82958 and by ACTH, but was not changed by
      SKF 38393 and was decreased by quinpirole. Super-stereotypy of the sequential
      pattern was produced only by dopamine D1 agonists. The relative probability of
      initiating the syntactical sequence was increased by both SKF 38393 and SKF
      82958, but was reduced by quinpirole and ACTH. The full D1 agonist, SKF 82958,
      also increased the likelihood that the pattern would be completed, thus causing
      sequential super-stereotypy in the strongest sense. Our results highlight a role
      for dopamine D1 receptors, probably within the basal ganglia, in the production
      of sequential super-stereotypy of complex behavioral patterns.

PMID- 10881041
TI  - Super-stereotypy I: enhancement of a complex movement sequence by systemic
      dopamine D1 agonists.
AB  - Peripheral administration of D1 dopamine agonists elicits grooming behavior from
      rodents. The present study examined grooming behavior and the relative
      probability and stereotypy of a natural sequence of grooming movements (called a
      syntactic grooming chain) that follows a predictable fixed pattern of serial
      order. We compared the amount of grooming behavior vs. the stereotypy of
      sequential patterns after peripheral administration of either a partial D1
      agonist (SKF 38393; 2.5, 5.0, 10, 20 mg/kg), a full D1 agonist (SKF 82958; 0.1,
      0.2, 0.5, 1.0 mg/kg; i.p.), a D2 agonist (quinpirole; 5.0, 10 mg/kg), or ACTH
      (2.0, 5.0 mg/kg). There was a dissociation between the elicited grooming amount,
      the pattern frequency, and the pattern completion or sequential stereotypy after
      these drugs. Quinpirole and ACTH both reduced the likelihood that the sequential
      pattern would be completed in the normal pattern (and reduced the overall amount
      of grooming). Administration of either SKF 38393 or SKF 82958 increased the
      tendency to engage in complex stereotyped sequential patterns of grooming (even
      though only the partial D1 agonist increased the total amount of grooming). In
      addition, SKF 38393 increased the sequential stereotypy of the already
      stereotyped pattern itself (as measured by the probability of completing the
      stereotyped sequence once it began). Thus, dopamine D1 receptor activation
      appears to contribute to a kind of sequential super-stereotypy in which a
      complex, stereotyped behavioral sequence is initiated more frequently and more
      often goes to completion.

PMID- 10881043
TI  - Tranylcypromine, but not moclobemide, prolongs the inhibitory action of dopamine
      on midbrain dopaminergic neurons: an in vitro electrophysiological study.
AB  - The degradation of dopamine by monoamine oxidase (MAO) enzymes plays an important
      role in the function of dopamine receptors in the central nervous system.
      Accordingly, it has already been reported that the blockade of MAO by specific
      inhibitors prolongs the effects of dopamine on its receptors. By using
      intracellular electrophysiological recordings, here we report that the
      irreversible MAO A and B inhibitor tranylcypromine, but not the reversible MAO A
      inhibitor moclobemide, potentiates DA responses in rat midbrain dopaminergic
      neurones maintained in vitro. Moclobemide was not effective even when the MAO B
      enzymes were additionally blocked by the MAOI deprenyl. Thus, our
      electrophysiological findings confirm that the degradation DA is very important
      to control the effects of this catecholamine at a cellular level. Furthermore,
      they demonstrate that tranylcypromine potentiates DA neurotransmission while
      moclobemide is devoid of dopaminergic action in an in vitro condition. The
      phenomena reported above support the hypothesis that part of the antidepressant
      and antiparkinsonian effects of tranylcypromine depend on an action on DA
      transmission.

PMID- 10881044
TI  - Cuneothalamic relay neurons are postsynaptic to glycine-immunoreactive terminals
      in the rat cuneate nucleus.
AB  - This study was aimed to clarify whether the cuneothalamic relay neurons (CTNs) in
      the rat cuneate nucleus contained glycine or whether the neurons were modulated
      directly by presynaptic glycine-IR terminals. For this purpose, retrograde
      transport of wheat germ agglutinin conjugated with horseradish peroxidase (WGA
      HRP) and immunoperoxidase labelling for glycine have been used to ascertain if
      the CTNs in the rat are glycine-immunoreactive (glycine-IR). Our results have
      shown that the WGA-HRP-labelled CTNs (mean area = 318 +/- 6.5 microm(2)) were not
      reactive for glycine. Glycine immunoreactivity, however, was localized in some
      small-sized neurons (mean area = 210 +/- 6.2 microm(2)) and axon terminals
      associated with the CTNs. The synaptic organization between the glycine-IR
      terminals and CTNs was further analyzed using anti-glycine postembedding
      immunogold labelling. By electron microscopy, the immunogold-labelled glycine-IR
      terminals containing pleomorphic synaptic vesicles formed symmetrical synaptic
      contacts with the dendrites, dendritic spines, and somata of CTNs. Quantitative
      estimation showed that the mean ratios of glycine-IR terminals to total terminals
      associated with the soma, proximal dendrites and distal dendrites of the CTN were
      49.5, 45.2, and 45.8%, respectively. The higher incidence of glycine-IR terminals
      on the soma, however, was not significantly different from that of the proximal
      and distal dendrites. Notwithstanding the above, this study has shown a large
      number of glycine-IR terminals making direct synaptic contacts with CTNs,
      suggesting that glycine is one of the important neurotransmitters involved in
      postsynaptic inhibition on the cuneothalamic relay neurons to modulate incoming
      somatosensory information from forelimb areas in the rat.

PMID- 10881045
TI  - [(3)H]PNU-101958, a D(4) dopamine receptor probe, accumulates in prefrontal
      cortex and hippocampus of non-human primate brain.
AB  - The D(4) dopamine receptor has been investigated for its potential role in
      neuropsychiatric disorders, "novelty-seeking" behaviors, and effects produced by
      some psychostimulants. An accurate map of D(4) distribution and density in brain
      is essential to clarify the role of this receptor subtype in normal brain
      function and in neuropsychiatric disorders. We investigated the autoradiographic
      distribution of D(4) receptors in non-human primate (Macaca mulatta) brain (N =
      3) with the novel D(4) receptor probe [(3)H]PNU-101958. Quantification of
      [(3)H]PNU-101958 binding sites in 77 brain regions revealed dense levels of D(4)
      receptors in several cortical areas, especially in prefrontal cortex, uncus,
      hypothalamic median eminence, hippocampal formation, and distinct thalamic
      nuclei, but were significantly lower in striatum. The results correspond well
      with previous reports of brain distribution of D(4) receptors using other
      radiolabeled probes, and of D(4) mRNA localization (with some exceptions).
      Overall, this study reveals that [(3)H]PNU-101958 binding sites in non-human
      primate brain appear to reflect D(4) dopamine receptor distribution. The
      significance of a dense localization of D(4) receptors in prefrontal cortex and
      hippocampus, and broad distribution in other brain areas, allows for
      investigation of the relationship of these receptors to specific neuropsychiatric
      disorders and effects produced by psychostimulants.

PMID- 10881046
TI  - Studies on ATP-diphosphohydrolase nucleotide-binding sites by intrinsic
      fluorescence.
AB  - Potato apyrase, a soluble ATP-diphosphohydrolase, was purified to homogeneity
      from several clonal varieties of Solanum tuberosum. Depending on the source of
      the enzyme, differences in kinetic and physicochemical properties have been
      described, which cannot be explained by the amino acid residues present in the
      active site. In order to understand the different kinetic behavior of the
      Pimpernel (ATPase/ADPase = 10) and Desiree (ATPase/ADPase = 1) isoenzymes, the
      nucleotide-binding site of these apyrases was explored using the intrinsic
      fluorescence of tryptophan. The intrinsic fluorescence of the two apyrases was
      slightly different. The maximum emission wavelengths of the Desiree and Pimpernel
      enzymes were 336 and 340 nm, respectively, suggesting small differences in the
      microenvironment of Trp residues. The Pimpernel enzyme emitted more fluorescence
      than the Desiree apyrase at the same concentration although both enzymes have the
      same number of Trp residues. The binding of the nonhydrolyzable substrate analogs
      decreased the fluorescence emission of both apyrases, indicating the presence of
      conformational changes in the neighborhood of Trp residues. Experiments with
      quenchers of different polarities, such as acrylamide, Cs+ and I- indicated the
      existence of differences in the nucleotide-binding site, as further shown by
      quenching experiments in the presence of nonhydrolyzable substrate analogs.
      Differences in the nucleotide-binding site may explain, at least in part, the
      kinetic differences of the Pimpernel and Desiree isoapyrases.

PMID- 10881047
TI  - Perinatal development and adult blood pressure.
AB  - A growing body of evidence supports the concept of fetal programming in
      cardiovascular disease in man, which asserts that an insult experienced in utero
      exerts a long-term influence on cardiovascular function, leading to disease in
      adulthood. However, this hypothesis is not universally accepted, hence animal
      models may be of value in determining potential physiological mechanisms which
      could explain how fetal undernutrition results in cardiovascular disease in later
      life. This review describes two major animal models of cardiovascular
      programming, the in utero protein-restricted rat and the cross-fostered
      spontaneously hypertensive rat. In the former model, moderate maternal protein
      restriction during pregnancy induces an increase in offspring blood pressure of
      20-30 mmHg. This hypertensive effect is mediated, in part, by fetal exposure to
      excess maternal glucocorticoids as a result of a deficiency in placental 11-ss
      hydroxysteroid dehydrogenase type 2. Furthermore, nephrogenesis is impaired in
      this model which, coupled with increased activity of the renin-angiotensin
      system, could also contribute to the greater blood pressure displayed by these
      animals. The second model discussed is the cross-fostered spontaneously
      hypertensive rat. Spontaneously hypertensive rats develop severe hypertension
      without external intervention; however, their adult blood pressure may be lowered
      by 20-30 mmHg by cross-fostering pups to a normotensive dam within the first two
      weeks of lactation. The mechanisms responsible for this antihypertensive effect
      are less clear, but may also involve altered renal function and down-regulation
      of the renin-angiotensin system. These two models clearly show that adult blood
      pressure is influenced by exposure to one of a number of stimuli during critical
      stages of perinatal development.

PMID- 10881048
TI  - Structural, functional and immunological studies on a polymeric bacterial
      protein.
AB  - The characterization of proteins from Brucella spp, the causative agent of
      brucellosis, has been the subject of intensive research. We have described an 18
      kDa cytoplasmic protein of Brucella abortus and shown the potential usefulness of
      this protein as an antigen for the serologic diagnosis of brucellosis. The amino
      acid sequence of the protein showed a low but significant homology with that of
      lumazine synthases. Lumazine is an intermediate product in bacterial riboflavin
      biosynthesis. The recombinant form of the 18-kDa protein (expressed in E. coli)
      folds like the native Brucella protein and has lumazine-synthase enzymatic
      activity. Three-dimensional analysis by X-ray crystallography of the homolog
      Bacillus subtilis lumazine synthase has revealed that the enzyme forms an
      icosahedral capsid. Recombinant lumazine synthase from B. abortus was
      crystallized, diffracted X rays to 2.7-A resolution at room temperature, and the
      structure successfully solved by molecular replacement procedures. The
      macromolecular assembly of the enzyme differs from that of the enzyme from B.
      subtilis. The Brucella enzyme remains pentameric (90 kDa) in its crystallographic
      form. Nonetheless, the active sites of the two enzymes are virtually identical at
      the structural level, indicating that inhibitors of these enzymes could be viable
      pharmaceuticals across a broad species range. We describe the structural reasons
      for the differences in their quaternary arrangement and also discuss the
      potential use of this protein as a target for the development of acellular
      vaccines.

PMID- 10881049
TI  - Role of gelatinases MMP-2 and MMP-9 in tissue remodeling following acute lung
      injury.
AB  - Acute lung injury is characterized by a severe disruption of alveolo-capillary
      structures and includes a variety of changes in lung cell populations. Evidence
      suggests the occurrence of rupture of the basement membranes and interstitial
      matrix remodeling during acute lung injury. The dynamic equilibrium of the
      extracellular matrix (ECM) under physiological conditions is a consequence of the
      balance between the regulation of synthesis and degradation of ECM components.
      Matrix metalloproteinases (MMPs) represent a group of enzymes involved in the
      degradation of most of the components of the ECM and therefore participate in
      tissue remodeling associated with pathological situations such as acute lung
      injury. MMP activity is regulated by proteolytic activation of the latent
      secreted proenzyme and by interaction with specific tissue inhibitors of
      metalloproteinases. This review details our knowledge of the involvement of MMPs,
      namely MMP-2 and MMP-9, in acute lung injury and acute respiratory distress
      syndrome.

PMID- 10881050
TI  - Standardization of a fluorimetric assay for the determination of tissue
      angiotensin-converting enzyme activity in rats.
AB  - The tripeptide Hip-His-Leu was used to standardize a fluorimetric method to
      measure tissue angiotensin-converting enzyme (ACE) activity in rats. The
      fluorescence of the o-phthaldialdehyde-His-Leu adduct was compared in the
      presence and absence of the homogenate (25 microl) to determine whether the
      homogenate from different tissues interfered with the fluorimetric determination
      of the His-Leu product. Only homogenates from lung and renal medulla and cortex
      showed significantly altered fluorescence intensity. To overcome this problem,
      the homogenate from these tissues were diluted 10 times with assay buffer. The
      specificity of the assay was demonstrated by the inhibition of ACE activity with
      3 microM enalaprilat (MK-422). There was a linear relationship between product
      formation and incubation time for up to 90 min for homogenates of renal cortex
      and medulla and liver, for up to 60 min for ventricles and adrenals and for up to
      30 min for the aorta, lung and atrium homogenates. In addition, there was a
      linear relationship between product formation and the amount of protein in the
      homogenates within the following range: lung, 30-600 microg; renal cortex and
      medulla, 40-400 microg; atrium and ventricles, 20-200 microg; adrenal, 20-100
      microg; aorta, 5-100 microg; liver, 5-25 microg. No peptidase activity against
      the His-Leu product (31 nmol), assayed in borate buffer (BB), was detected in the
      different homogenates except the liver homogenate, which was inhibited by 0.1 mM
      rho-chloromercuribenzoic acid. ACE activity in BB was higher than in phosphate
      buffer (PB) due, at least in part, to a greater hydrolysis of the His-Leu product
      in PB. ACE activity of lung increased 20% when BB plus Triton was used. Enzyme
      activity was stable when the homogenates were stored at -20o or -70oC for at
      least 30 days. These results indicate a condition whereby ACE activity can be
      easily and efficiently assayed in rat tissue samples homogenized in BB using a
      fluorimetric method with Hip-His-Leu as a substrate.

PMID- 10881051
TI  - Development of an operational substrate for ZapA, a metalloprotease secreted by
      the bacterium Proteus mirabilis.
AB  - The protease ZapA, secreted by Proteus mirabilis, has been considered to be a
      virulence factor of this opportunistic bacterium. The control of its expression
      requires the use of an appropriate methodology, which until now has not been
      developed. The present study focused on the replacement of azocasein with
      fluorogenic substrates, and on the definition of enzyme specificity. Eight
      fluorogenic substrates were tested, and the peptide Abz-Ala-Phe-Arg-Ser-Ala-Ala
      Gln-EDDnp was found to be the most convenient for use as an operational substrate
      for ZapA. A single peptide bond (Arg-Ser) was cleaved with a Km of 4.6 microM, a
      k cat of 1.73 s-1, and a catalytic efficiency of 376 (mM s)-1. Another good
      substrate for ZapA was peptide 6 (Abz-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-Gln
      EDDnp) which was cleaved at a single bond (Phe-Ser) with a Km of 13.6 microM, a k
      cat of 3.96 s-1 and a catalytic efficiency of 291 (mM s)-1. The properties of the
      amino acids flanking the scissile bonds were also evaluated, and no clear
      requirement for the amino acid residue at P1 was found, although the enzyme seems
      to have a preference for a hydrophobic residue at P2.

PMID- 10881052
TI  - Expression and biological activity of two recombinant polypeptides related to
      subunit 1 of the interferon-alpha receptor.
AB  - Abnormal production of interferon alpha (IFN-alpha) has been found in certain
      autoimmune diseases and can be also observed after prolonged therapy with IFN
      alpha. IFN-alpha can contribute to the pathogenesis of allograft rejection in
      bone marrow transplants. Therefore, the development of IFN-alpha inhibitors as a
      soluble receptor protein may be valuable for the therapeutic control of these
      diseases. We have expressed two polypeptides encoding amino acids 93-260 (P1) and
      261-410 (P2) of the extracellular domain of subunit 1 of the interferon-alpha
      receptor (IFNAR 1-EC) in E. coli. The activities of the recombinant polypeptides
      and of their respective antibodies were evaluated using antiproliferative and
      antiviral assays. Expression of P1 and P2 polypeptides was achieved by
      transformation of cloned plasmid pRSET A into E. coli BL21(DE3)pLysS and by IPTG
      induction. P1 and P2 were purified by serial sonication steps and by gel
      filtration chromatography with 8 M urea and refolded by dialysis. Under reducing
      SDS-PAGE conditions, the molecular weight of P1 and P2 was 22 and 17 kDa,
      respectively. Polyclonal anti-P1 and anti-P2 antibodies were produced in mice. P1
      and P2 and their respective polyclonal antibodies were able to block the
      antiproliferative activity of 6.25 nM IFN-alphaB on Daudi cells, but did not
      block IFN-alphaB activity at higher concentrations (>6. 25 nM). On the other
      hand, the polypeptides and their respective antibodies did not inhibit the
      antiviral activity of IFN-alphaB on Hep 2/c cells challenged with
      encephalomyocarditis virus.

PMID- 10881053
TI  - Treatment of cytomegalovirus retinitis with an intraocular sustained-release
      ganciclovir implant.
AB  - The objective of this prospective study was to evaluate the efficacy and
      complications of the use of an intraocular sustained-release ganciclovir implant
      for the treatment of active cytomegalovirus (CMV) retinitis in AIDS patients.
      Thirty-nine eyes of 26 patients were submitted to ocular surgery. All patients
      underwent complete ocular examination before and after surgery. The surgical
      procedure was always done under local anesthesia using the same technique. The
      mean time for the surgical procedure was 20 min (range, 15 to 30 min). The
      average follow-up period was 3.7 months. Of all patient, only 4 presented
      recurrence of retinitis after 8, 8, 9 and 2 months, respectively. Three of them
      received a successful second implant. All 39 eyes of the 26 patients presented
      healing of retinitis as shown by clinical improvement evaluated by indirect
      binocular ophthalmoscopy and retinography. Retinitis healed within a period of 4
      to 6 weeks in all patients, with clinical regression signs from the third week
      on. Six (15.4%) eyes developed retinal detachment. None of the patients developed
      CMV retinitis in the contralateral eye. The intraocular implant proved to be
      effective in controlling the progression of retinitis for a period of up to 8
      months even in patients for whom systemic therapy with either ganciclovir or
      foscarnet or both had failed. The intraocular sustained-release ganciclovir
      implant proved to be a safe new procedure for the treatment of CMV retinitis,
      avoiding the systemic side effects caused by the intravenous medications and
      improving the quality of life of the patients.

PMID- 10881054
TI  - Amifostine (WR-2721), a cytoprotective agent during high-dose cyclophosphamide
      treatment of non-Hodgkin's lymphomas: a phase II study.
AB  - Clinical trials indicate that amifostine may confer protection on various normal
      tissues without attenuating anti-tumor response. When administered prior to
      chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection
      including against alkylating drugs. The mechanism of protection resides in the
      metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity
      of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia
      being observed. We report a phase II study using amifostine as a protective drug
      against high-dose cyclophosphamide (HDCY) (7 g/m2), used to mobilize peripheral
      blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29
      patients, 22 (75. 9%) affected by aggressive and 7 (24.1%) by indolent non
      Hodgkin's lymphoma (NHL), who were submitted to 58 infusions of amifostine and
      compared them with a historical group (33 patients) affected by aggressive NHL
      and treated with VACOP-B followed by HDCY. The most important results in favor of
      amifostine were the reduction of intensity of cardiac, pulmonary and hepatic
      toxicity, and a significant reduction of frequency and severity of mucositis (P =
      0. 04). None of the 29 patients died in the protected group, while in the
      historical group 2/33 patients died because of cardiac or pulmonary toxicity and
      2 patients stopped therapy due to toxicity. Amifostine did not prevent the
      aplastic phase following HDCY. PBPC collection and hematological recovery were
      adequate in both groups. The number of CFU-GM (colony-forming units
      granulocyte/macrophage) colonies and mononuclear cells in the apheresis products
      was significantly higher in the amifostine group (P = 0.02 and 0.01,
      respectively). Side effects were mild and easily controlled. We conclude that
      amifostine protection should be useful in HDCY to protect normal tissues, with
      acceptable side effects.

PMID- 10881055
TI  - Familial predisposition to hypertension and the association between urinary
      sodium excretion and blood pressure in a population-based sample of young adults.
AB  - The reasons for the inconsistent association between salt consumption and blood
      pressure levels observed in within-society surveys are not known. A total of 157
      normotensive subjects aged 18 to 35 years, selected at random in a cross
      sectional population-based survey, answered a structured questionnaire. They were
      classified as strongly predisposed to hypertension when two or more first-degree
      relatives had a diagnosis of hypertension. Anthropometric parameters were
      obtained and sitting blood pressure was determined with aneroid
      sphygmomanometers. Sodium and potassium excretion was measured by flame
      spectrophotometry in an overnight urine sample. A positive correlation between
      blood pressure and urinary sodium excretion was detected only in the group of
      individuals strongly predisposed to hypertension, both for systolic blood
      pressure (r = 0.51, P<0.01) and diastolic blood pressure (r = 0.50, P<0.01). In a
      covariance analysis, after controlling for age, skin color and body mass index,
      individuals strongly predisposed to hypertension who excreted amounts of sodium
      above the median of the entire sample had higher systolic and diastolic blood
      pressure than subjects classified into the remaining conditions. The influence of
      familial predisposition to hypertension on the association between salt intake
      and blood pressure may be an additional explanation for the weak association
      between urinary sodium excretion and blood pressure observed in within-population
      studies, since it can influence the association between salt consumption and
      blood pressure in some but not all inhabitants.

PMID- 10881057
TI  - The hemolytic component of cancer anemia: effects of osmotic and metabolic stress
      on the erythrocytes of rats bearing multifocal inoculations of the Walker 256
      tumor.
AB  - Cancer anemia is classified as an anemia of chronic diseases, although it is
      sometimes the first symptom of cancer. Cancer anemia includes a hemolytic
      component, important in the terminal stage when even transfused cells are rapidly
      destroyed. The presence of a chronic component and the terminal complications of
      the illness limit studies of the hemolytic component. A multifocal model of tumor
      growth was used here to simulate the terminal metastatic dissemination stage
      (several simultaneous inoculations of Walker 256 cells). The hemolytic component
      of anemia began 3-4 days after inoculation in 100% of the rats and progressed
      rapidly thereafter: Hb levels dropped from 14.9 +/- 0.02 to 8.7 +/- 0.06 from
      days 7 to 11 ( approximately 5 times the physiologically normal rate in rats) in
      the absence of bleeding. The development of anemia was correlated (r2 = 0.86)
      with the development of other systemic effects such as anorexia. There was a
      significant decrease in the osmotic fragility of circulating erythrocytes: the
      NaCl concentration causing 50% lysis was reduced from 4.52 +/- 0.06 to 4.10 +/-
      0.01 (P<0.01) on day 7, indicating a reduction in erythrocyte volume. However,
      with mild metabolic stress (4-h incubation at 37oC), the erythrocytes showed a
      greater increase in osmotic fragility than the controls, suggesting marked
      alteration of erythrocyte homeostasis. These effects may be due to primary plasma
      membrane alterations (transport and/or permeability) and/or may be secondary to
      metabolic changes. This multifocal model is adequate for studying the hemolytic
      component of cancer anemia since it is rapid, highly reproducible and causes
      minimal animal suffering.

PMID- 10881056
TI  - Time sequence of changes in the responsiveness of glycogen breakdown to
      adrenergic agonists in perfused liver of rats with insulin-induced hypoglycemia.
AB  - The time-course changes of the responsiveness of glycogen breakdown to alpha- and
      ss-adrenergic agonists during insulin-induced hypoglycemia (IIH) were
      investigated. Blood glucose levels were decreased prior to the alteration in the
      hepatic responsiveness to adrenergic agonists. The activation of hepatic glucose
      production and glycogenolysis by phenylephrine (2 microM) and isoproterenol (20
      microM) was decreased in IIH. The changes in the responsiveness of glycogen
      catabolism were first observed for isoproterenol and later for phenylephrine.
      Hepatic ss-adrenergic receptors showed a higher degree of adrenergic
      desensitization than did alpha-receptors. Liver glycogen synthase activity,
      glycogen content and the catabolic effect of dibutyryl cyclic AMP (the ss
      receptor second messenger) were not affected by IIH.

PMID- 10881058
TI  - The use of filter paper plasticized with polyvinyl alcohol-glutaraldehyde in
      ELISA.
AB  - F1-antigen purified from Yersinia pestis was covalently linked to 5-mm diameter
      filter paper discs plasticized with polyvinyl alcohol-glutaraldehyde. These discs
      were used both for ELISA and dot-ELISA for the detection of anti-F1 IgG in
      rabbits. The best conditions were achieved using 1.25 microg of F1 antigen/disc,
      3% w/v skim milk in PBS as blocking agent, anti-IgG peroxidase conjugate diluted
      12,000 times, and serum from rabbits immunized or not against Y. pestis, diluted
      6,400 times. The absorbance values obtained from the comparative study between
      this procedure and conventional ELISA were not significantly different but the
      low cost of the reagents employed in ELISA using the filter paper discs
      plasticized with polyvinyl alcohol-glutaraldehyde makes this method economically
      attractive.

PMID- 10881059
TI  - Infusions of AP5 into the basolateral amygdala impair the formation, but not the
      expression, of step-down inhibitory avoidance.
AB  - We evaluated the effects of infusions of the NMDA receptor antagonist D,L-2-amino
      5-phosphonopentanoic acid (AP5) into the basolateral nucleus of the amygdala
      (BLA) on the formation and expression of memory for inhibitory avoidance. Adult
      male Wistar rats (215-300 g) were implanted under thionembutal anesthesia (30
      mg/kg, ip) with 9.0-mm guide cannulae aimed 1.0 mm above the BLA. Bilateral
      infusions of AP5 (5.0 microg) were given 10 min prior to training, immediately
      after training, or 10 min prior to testing in a step-down inhibitory avoidance
      task (0.3 mA footshock, 24-h interval between training and the retention test
      session). Both pre- and post-training infusions of AP5 blocked retention test
      performance. When given prior to the test, AP5 did not affect retention. AP5 did
      not affect training performance, and a control experiment showed that the
      impairing effects were not due to alterations in footshock sensitivity. The
      results suggest that NMDA receptor activation in the BLA is involved in the
      formation, but not the expression, of memory for inhibitory avoidance in rats.
      However, the results do not necessarily imply that the role of NMDA receptors in
      the BLA is to mediate long-term storage of fear-motivated memory within the
      amygdala.

PMID- 10881060
TI  - Protective effect of policosanol on atherosclerotic lesions in rabbits with
      exogenous hypercholesterolemia.
AB  - Policosanol is a mixture of higher aliphatic alcohols purified from sugar cane
      wax, with cholesterol-lowering effects demonstrable in experimental models and in
      patients with type II hypercholesterolemia. The protective effects of policosanol
      on atherosclerotic lesions experimentally induced by lipofundin in rabbits and
      rats and spontaneously developed in stumptail monkeys have been described. The
      present study was conducted to determine whether policosanol administered orally
      to rabbits with exogenous hypercholesterolemia also protects against the
      development of atherosclerotic lesions. Male New Zealand rabbits weighing 1.5 to
      2 kg were randomly divided into three experimental groups which received 25 or
      200 mg/kg policosanol (N = 7) orally for 60 days with acacia gum as vehicle or
      acacia gum alone (control group, N = 9). All animals received a cholesterol-rich
      diet (0.5%) during the entire period. Control animals developed marked
      hypercholesterolemia, macroscopic lesions and arterial intimal thickening. Intima
      thickness was significantly less (32.5 +/- 7 and 25.4 +/- 4 microm) in
      hypercholesterolemic rabbits treated with policosanol than in controls (57.6 +/-
      9 microm). In most policosanol-treated animals, atherosclerotic lesions were not
      present, and in others, thickness of fatty streaks had less foam cell layers than
      in controls. We conclude that policosanol has a protective effect on the
      atherosclerotic lesions occurring in this experimental model.

PMID- 10881061
TI  - Novel methods for the encapsulation of meglumine antimoniate into liposomes.
AB  - The antimonial drug, meglumine antimoniate, was successfully encapsulated in
      dehydration-rehydration vesicles and in freeze-dried empty liposomes (FDELs).
      High encapsulation efficiencies (from 28 to 58%) and low weight ratios of lipids
      to encapsulated antimony (from 1:0.15 to 1:0.3) were achieved. These
      formulations, contrary to those obtained by conventional methods, can be stored
      as intermediate lyophilized forms and reconstituted just before use. The efficacy
      of FDEL-encapsulated meglumine antimoniate was evaluated in hamsters
      experimentally infected with Leishmania chagasi. A significant reduction of liver
      parasite burdens was observed in animals treated with this preparation, when
      compared to control animals treated with empty liposomes. In contrast, free
      meglumine antimoniate was found to be inefficient when administered at a
      comparable dose of antimony. This novel liposome-based meglumine antimoniate
      formulation appears to be promising as a pharmaceutical product for the treatment
      of visceral leishmaniasis.

PMID- 10881062
TI  - Dietary sodium intake induced myenteric neuron hypertrophy in Wistar rats.
AB  - In the present study we investigated the effect of salt intake on myenteric
      neuron size of the colon of adult male Wistar rats. The animals were placed on
      either a high-salt (HS; 8%; 12 animals) or a low-salt diet (LS; 0.15%; 12
      animals) for 15 or 52 weeks and blood pressure was measured. The sizes of
      myenteric neurons of the distal colon from both groups were measured. No
      difference in neuron size was observed between the HS and LS groups after 15
      weeks. After 52 weeks on HS, neuron size was increased (P<0.005) when compared
      with the LS group. The rats also presented hypertension, which was significantly
      different at 52 weeks (142 +/- 11 vs 119 +/- 7 mmHg). These results suggest that
      a long time on an HS diet can significantly increase myenteric nerve cell size.

PMID- 10881063
TI  - Neonatal chronic lung disease.

PMID- 10881064
TI  - Use of corticosteroids and the outcome of infants with bronchopulmonary
      dysplasia.
AB  - Ventilator-dependent premature infants are often treated with dexamethasone.
      Several trials showed that steroids while improve pulmonary compliance and
      facilitate extubation, some treated infants may have adverse effects, such as
      alterations of growth curves. We conducted this retrospective study to evaluate
      the effects of steroids on mechanical ventilation, oxygen therapy, hospital
      length stay and mortality, in ventilator-dependent infants with bronchopulmonary
      dysplasia (BPD) (defined as the need of oxygen supplementation at 28 days of
      life). Twenty-six newborns with BPD were evaluated during 9 - 42 days postpartum
      (mean = 31 days) and were divided into two groups: Group I - 14 newborns that did
      not receive dexamethasone, and Group II - 12 newborns that received dexamethasone
      at 14 - 21 days of life. Dexamethasone was given at a dose of 0.25 mg per
      kilogram of body weight twice daily intravenously for 3 days, after which the
      dose was tapered. RESULTS: There were no statistically significant differences in
      the mean length of mechanical ventilation (Group I - 37 days, Group II - 35
      days); oxygen supplementation (Group I - 16 days, Group II - 29 days); hospital
      stay (Group I - 72 days, Group II - 113 days); mortality (Group I - 35.7%, Group
      II - 41.6%). At birth, Group II was lighter (BW: Group I - 1154 grams +/- 302,
      Group II - 791 grams +/- 165; p < 0.05) and smaller (height: Group I - 37.22 cm
      +/- 3.3, Group II - 33.5 +/- 2.4; p< 0.05) than Group I. At 40 weeks, there were
      no statistically significant differences between groups in relation to
      anthropometric measurements. CONCLUSIONS: The use of corticosteroids in
      bronchopulmonary dysplasic infants may influence the somatic growth during its
      use. However, after its suspension, a recovery seems to occur, suggesting that
      its influence could be transitory.

PMID- 10881065
TI  - Experimental determination of bone cortex holding power of orthopedic screw.
AB  - Cylindrical specimens of bone measuring 15 mm in diameter were obtained from the
      lateral cortical layer of 10 pairs of femurs and tibias. A central hole 3.2 mm in
      diameter was drilled in each specimen. The hole was tapped, and a 4.5 mm cortical
      bone screw was inserted from the outer surface. The montage was submitted to push
      out testing up to a complete strip of the bone threads. The cortical thickness
      and rupture load were measured, and the shear stress was calculated. The results
      were grouped according to the bone segment from which the specimen was obtained.
      The results showed that bone cortex screw holding power is dependent on the bone
      site. Additionally, the diaphyseal cortical bone tissue is both quantitatively
      and qualitatively more resistant to screw extraction than the metaphyseal tissue.

PMID- 10881066
TI  - Bowel preparation for colonoscopy: comparison of mannitol and sodium phosphate.
      Results of a prospective randomized study.
AB  - METHOD: Eighty patients were prospectively randomized for precolonoscopic
      cleansing either with 750ml of 10% mannitol (Group M) or 180ml of a sodium
      phosphate preparation (Group NaP). Laboratory examinations before and after
      preparation on all patients included hemoglobin, hematocrit, sodium, potassium,
      phosphorous, calcium and serum osmolarity. A questionnaire was used to assess
      undesirable side effects and patient tolerance to the solution. The quality of
      preparation was assessed by the endoscopist who was unaware of the solution
      employed. RESULTS: Statistically significant changes were verified in serum
      sodium, phosphorous, potassium and calcium between the two groups, but no
      clinical symptoms were observed. There were no significant differences in the
      frequency of side effects studied. Six of the eight patients in Group NaP who had
      taken mannitol for a previous colonoscopy claimed better acceptance of the sodium
      phosphate solution. The endoscopic-blinded trial reported excellent or good bowel
      preparation in 85% prepared with sodium phosphate versus 82.5% for mannitol
      (p=0.37). CONCLUSIONS: Quality of preparation and frequency of side effects was
      similar in the two solutions. The smaller volume of sodium phosphate necessary
      for preparation seems to be related to its favorable acceptance. Nevertheless,
      the retention of sodium and phosphate ions contraindicates the use of sodium
      phosphate in patients with renal failure, cirrhosis, ascites, and heart failure.

PMID- 10881067
TI  - Size of gastroesophageal varices: its behavior after the surgical treatment of
      portal hypertension.
AB  - The size of gastroesophageal varices is one of the most important factors leading
      to hemorrhage related to portal hypertension. An endoscopic evaluation of the
      size of gastroesophageal varices before and after different operations for portal
      hypertension was performed in 73 patients with schistosomiasis, as part of a
      randomized trial: proximal splenorenal shunt (PSS n=24), distal splenorenal shunt
      (DSS n=24), and esophagogastric devascularization with splenectomy (EGDS n=25).
      The endoscopic evaluation was performed before and up to 10 years after the
      operations. Variceal size was graded according to Palmer's classification: grade
      1 - up to 3 mm, grade 2 - from 3 to 6 mm, grade 3 - greater than 6 mm, and were
      analyzed in four anatomical locations: inferior, middle or superior third of the
      esophagus, and proximal stomach. The total number of points in the pre-operative
      grading minus the number of points in the post-operative grading gave a
      differential grading, allowing statistical comparison among the surgical groups.
      Good results, in terms of disappearance or decrease of variceal size, were
      observed more frequently after PSS than after DSS or EGDS - 95.8%, 83.3%, and
      72%, respectively. When differential grading was analyzed, a statistically
      significant difference was observed between PSS and EGDS, but not between
      proximal and distal splenorenal shunts. In conclusion, shunt surgeries were more
      efficient than devascularization in diminishing variceal size.

PMID- 10881068
TI  - Effectiveness of silver nitrate compared to talc slurry as pleural sclerosing
      agent in rabbits. Influence of concomitant intrapleural lidocaine.
AB  - The ideal agent for producing pleurodesis has not been identified. Talc, the most
      commonly used, poses several problems. Another possibility is silver nitrate,
      which was widely used in the past. PURPOSE: To determine the influence of the
      intrapleural instillation of lidocaine in producing a pleurodesis with silver
      nitrate, to define the effect of lidocaine in the maturation of the collagen
      fibers, and to confirm that the pleurodesis after silver nitrate is stronger than
      after talc. METHODS: We studied three groups of 8 rabbits. Two groups received
      0.5% silver nitrate; in one we had previously injected 0.5 ml of 2% lidocaine.
      The third group received 400 mg/kg talc (2 ml). The animals were sacrificed 28
      days after the injection, and the pleural spaces were assessed grossly for
      evidence of pleurodesis and microscopically for evidence of inflammation and
      fibrosis. The total amount of pleural collagen and the distribution of thick and
      thin collagen fibers were quantified. Collagen was identified using picrosirius
      red stain. RESULTS: In the two groups that received silver nitrate (without
      lidocaine: 3.5 + 03 and with lidocaine: 3.2 + 0.3), the macroscopic pleurodesis
      (scale 0 - 4) was significantly (p = 0.001) better than that resulting from talc
      (1.6 + 0.2). The mean degree of pleural fibrosis induced by silver nitrate (3.5 +
      0.2) was significantly (p = 0.004) higher than that induced by talc (1.9 + 0.1).
      The previous instillation of lidocaine resulted in a tendency for decreased
      amounts of fibrosis (3.1 + 0.4). The mean amount (10(3)mm2) of pleural collagen
      was significantly (p = 0.009) greater in the rabbits that received silver nitrate
      (116.9 + 22.7) than in those that received talc (10.7 + 3.4). The injection of
      lidocaine slightly reduced the collagen (80.1 + 30.3). The distribution of
      collagen fibers did not differ among the groups. CONCLUSION: This rabbit model
      clearly confirms that intrapleural silver nitrate is more effective than talc for
      producing pleurodesis. The previous intrapleural instillation of lidocaine
      results in a decreasing trend in the amount of collagen, but does not change the
      effectiveness of the pleural fusion or modify the process of collagen maturation.

PMID- 10881069
TI  - Elimination of biliary stones through the urinary tract: a complication of the
      laparoscopic cholecystectomy.
AB  - The introduction and popularization of laparoscopic cholecystectomy has been
      accompanied with a considerable increase in perforation of gallbladder during
      this procedure (10% - 32%), with the occurrence of intraperitoneal bile spillage
      and the consequent increase in the incidence of lost gallstones (0.2% - 20%).
      Recently the complications associated with these stones have been documented in
      the literature. We report a rare complication occurring in an 81-year-old woman
      who underwent laparoscopic cholecystectomy and developed cutaneous fistula to the
      umbilicus and elimination of biliary stones through the urinary tract. During the
      cholecystectomy, the gall bladder was perforated, and bile and gallstones were
      spilled into the peritoneal cavity. Two months after the initial procedure there
      was exteriorization of fistula through the umbilicus, with intermittent
      elimination of biliary stones. After eleven months, acute urinary retention
      occurred due to biliary stones in the bladder, which were removed by cystoscopy.
      We conclude that efforts should be concentrated on avoiding the spillage of
      stones during the surgery, and that no rules exist for indicating a laparotomy
      simply to retrieve these lost gallstones.

PMID- 10881070
TI  - Relationship between obsessive-compulsive disorders and diseases affecting
      primarily the basal ganglia.
AB  - Obsessive-compulsive disorder (OCD) has been reported in association with some
      neurological diseases that affect the basal ganglia such as Tourette's syndrome,
      Sydenham's chorea, Parkinson's disease, and Huntington's disease. Furthermore,
      studies such as neuroimaging, suggest a role of the basal ganglia in the
      pathophysiology of OCD. The aim of this paper is to describe the association of
      OCD and several neurologic disorders affecting the basal ganglia, report the
      existing evidences of the role of the basal ganglia in the pathophysiology of
      OCD, and analyze the mechanisms probably involved in this pathophysiology.

PMID- 10881071
TI  - Clinical and laboratory assessment of nutritional status.

PMID- 10881072
TI  - Nutritional follow-up of critically ill infants receiving short term parenteral
      nutrition.
AB  - Few studies have tried to characterize the efficacy of parenteral support of
      critically ill infants during short period of intensive care. We studied
      seventeen infants during five days of total parenteral hyperalimentation.
      Subsequently, according to the clinical conditions, the patients received
      nutritional support by parenteral, enteral route or both up to the 10th day.
      Evaluations were performed on the 1st, 5th, and 10th days. These included:
      clinical data (food intake and anthropometric measurements), haematological data
      (lymphocyte count), biochemical tests (albumin, transferrin, fibronectin,
      prealbumin, retinol-binding protein) and hormone assays (cortisol, insulin,
      glucagon). Anthropometric measurements revealed no significant difference between
      the first and second evaluations. Serum albumin and transferrin did not change
      significantly, but mean values of fibronectin (8.9 to 16 mg/dL), prealbumin (7.7
      to 18 mg/dL), and retinol-binding protein (2.4 to 3. 7 mg/dL) increased
      significantly (p < 0.05) from the 1st to the 10th day. The hormonal study showed
      no difference for insulin, glucagon, and cortisol when the three evaluations were
      compared. The mean value of the glucose/insulin ratio was of 25.7 in the 1st day
      and 15. 5 in the 5th day, revealing a transitory supression of this hormone.
      Cortisol showed values above normal in the beginning of the study. We conclude
      that the anthropometric parameters were not useful due to the short time of the
      study; serum proteins, fibronectin, prealbumin, and retinol-binding protein were
      very sensitive indicators of nutritional status, and an elevated glucose/insulin
      ratio, associated with a slight tendency for increased cortisol levels suggest
      hypercatabolic state. The critically ill patient can benefit from an early
      metabolic support.

PMID- 10881073
TI  - Urinary tract infection in full-term newborn infants: risk factor analysis.
AB  - OBJECTIVE: To analyze the correlation of risk factors to the occurrence of
      urinary tract infection in full-term newborn infants. PATIENTS AND METHODS:
      Retrospective study (1997) including full-term infants having a positive urine
      culture by bag specimen. Urine collection was based on: fever, weight loss > 10%
      of birth weight, nonspecific symptoms (feeding intolerance, failure to thrive,
      hypoactivity, debilitate suction, irritability), or renal and urinary tract
      malformations. In these cases, another urine culture by suprapubic bladder
      aspiration was collected to confirm the diagnosis. To compare and validate the
      risk factors in each group, the selected cases were divided into two groups:
      Group I - positive urine culture by bag specimen collection and negative urine
      culture by suprapubic aspiration, and Group II - positive urine culture by bag
      specimen collection and positive urine culture by suprapubic aspiration. RESULTS:
      Sixty one infants were studied, Group I, n = 42 (68.9%) and Group II, n = 19
      (31.1%). The selected risk factors (associated infectious diseases, use of broad
      spectrum antibiotics, renal and urinary tract malformations, mechanical
      ventilation, parenteral nutrition and intravascular catheter) were more frequent
      in Group II (p<0.05). Through relative risk analysis, risk factors were, in
      decreasing importance: parenteral nutrition, intravascular catheter, associated
      infectious diseases, use of broad-spectrum antibiotics, mechanical ventilation,
      and renal and urinary tract malformations. CONCLUSION: The results showed that
      parenteral nutrition, intravascular catheter, and associated infectious diseases
      contributed to increase the frequency of neonatal urinary tract infection, and in
      the presence of more than one risk factor, the occurrence of urinary tract
      infection rose up to 11 times.

PMID- 10881074
TI  - Mullerian adenosarcoma of the uterus with sarcomatous overgrowth following
      tamoxifen treatment for breast cancer.
AB  - Mullerian adenosarcoma with sarcomatous overgrowth presented by a 52-year-old
      female patient after adjuvant tamoxifen treatment for breast carcinoma is
      described. The diagnosis was made on histological basis after curettage and
      complementary total hysterectomy with bilateral salpingo-oophorectomy. The
      immunohistochemical study showed high expression of estrogen receptors in the
      epithelial component of the lesion and irregularly positive findings in the
      stroma. The proliferative activity evaluated by Ki-67 immunoexpression was higher
      in the stroma than the epithelium. Some of the stromal cells showed
      rhabdomyoblastic differentiation. The association of tamoxifen use and
      development of mesenchymal neoplasms is discussed.

PMID- 10881075
TI  - Rat allotransplantation of epigastric microsurgical flaps: a study of rejection
      and the immunosuppressive effect of cyclosporin A.
AB  - The rejection of allotransplantation of epigastric microsurgical flaps and the
      effect of immunosuppression have been studied in 58 rats. Three sets of
      experiments were planned: (1) Wistar Furth isogenic donors and receptors (control
      set); (2) Brown Norway donors and Wistar Furth receptors (rejection set); and (3)
      Brown Norway donors and Wistar Furth immunosuppressed receptors (cyclosporin A
      set). Cyclosporin A (10 mg/kg/d) treated rats had a transplantation survival rate
      of up to 30 days: 83.3% among isogenic animals and 60% among allogeneic. There
      was 100% rejection by the 9th day after the transplantation in allogeneic non
      immunosuppressed rats. Biopsies embedded with historesin were taken from the flap
      and normal contralateral skin (used as control) on the 3rd, 7th, 15th, and 30th
      days after the surgery. A quantitative study of infiltrating lymphocytes in the
      flaps, with and without cyclosporin A, was done by evaluating the local
      inflammatory infiltrate. A significant increase in the number of lymphocytes
      among the rejection and immunosuppressed groups was seen, as compared to the
      isogenic set. Local lymphocytosis in allogeneic non-immunosuppressed
      transplantations reached its highest level on the 3rd day after surgery, before
      gross findings of rejection, which could only be seen by naked eye on the 5th or
      6th day. Therefore, we conclude that cyclosporin A is effective in preserving
      allogenic transplantation in rats. Biopsies of transplanted areas may contribute
      to earlier diagnosis of the need for immunosuppressive therapy.

PMID- 10881076
TI  - Blue rubber bleb nevus syndrome.
AB  - The blue rubber nevus syndrome consists of multiple venous malformations in the
      skin and gastrointestinal tract associated with intestinal hemorrhage and iron
      deficiency anemia. Other organs may be involved. The causes of this syndrome are
      unknown. Its most common presentation is in the form of sporadic cases, but
      dominant autosomal inheritance has been described. It is a condition that affects
      both sexes equally, and its occurrence is rare in the black race. We present a
      case of this syndrome diagnosed in a 11-year-old patient. He had severe anemia
      and a venous swelling on the trunk. Similar lesions were found in the stomach,
      bowel, and on his foot. We emphasize the main clinical aspects: intestine, eyes,
      nasopharynx, parotids, lungs, liver, spleen, heart, brain, pleura, peritoneum,
      pericardium, skeletal muscles, bladder, and penis lesions, systemic complications
      that may occur to these patients which are thrombosis and calcification, as well
      as consumptive coagulopathy and thrombocytopenia that may occur within the nevi.

PMID- 10881077
TI  - Colorectal cancer screening.
AB  - Colorectal cancer (CRC) is the third most common cancer in the world, and
      mortality has remained the same for the past 50 years, despite advances in
      diagnosis and treatment. Because significant numbers of patients present with
      advanced or incurable stages, patients with pre-malignant lesions (adenomatous
      polyps) that occur as result of genetic inheritance or age should be screened,
      and patients with long-standing inflammatory bowel disease should undergo
      surveillance. There are different risk groups for CRC, as well as different
      screening strategies. It remains to be determined which screening protocol is the
      most cost-effective for each risk catagory. The objective of screening is to
      reduce morbidity and mortality in a target population. The purpose of this review
      is to analyze the results of the published CRC screening studies, with regard to
      the measured reduction of morbidity and mortality, due to CRC in the studied
      populations, following various screening procedures. The main screening
      techniques, used in combination or alone, include fecal occult blood tests,
      flexible sigmoidoscopy, and colonoscopy. Evidence from the published literature
      on screening methods for specific risk groups is scanty and frequently does not
      arise from controlled studies. Nevertheless, data from these studies, combined
      with recent advances in molecular genetics, certainly lead the way to greater
      efficacy and lower cost of CRC screening.

PMID- 10881078
TI  - [Isolation of Rickettsia in vero cell culture].
AB  - The diagnosis of spotted fever is based on characteristic signs and symptoms but
      requires laboratorial confirmation because of the possible differential diagnosis
      from other diseases like leptospirosis, enterovirus, meningococcemia and typhoid
      fever. Laboratorial confirmation may be done by detection of specific antibodies
      which is possible only 5-10 days after the onset of the symptoms or by the
      isolation of Rickettsiae from blood and/or skin biopsy and from ticks collected
      in the patient or in the animal reservoir. The isolation of Rickettsiae from
      blood or skin biopsy results in an early diagnosis of spotted fever since in the
      rickettsiemic phase of the disease there is no detectable level of antibodies in
      the serum. With the purpose of facilitating the diagnosis of Spotted Fever we
      have standardized the isolation of Rickettsiae in cell culture by a method that
      is less time consuming and that reduces the biological risks than isolation in
      guinea pigs. Vero cell cultures were inoculated with the Sheyla Smith strain of
      Rickettsia rickettsii provided by CDC (Atlanta-USA). The identification was
      performed by indirect immunofluorescence technique. The presence of green
      fluorescent organisms characterized the growth of the agent. Ulterior
      confirmation of the methodology was done by isolation of the spotted fever agent
      from skin biopsy of a patient from an endemic area and from Amblyomma ticks that
      are the reservoir and vector of the Brazilian spotted fever.

PMID- 10881079
TI  - [Protective effect of benznidazole against parasite reactivation in patients
      chronically infected with Trypanosoma cruzi and treated with corticoids for
      associated diseases].
AB  - Patients in the chronic phase of Chagas' disease and receiving corticoid because
      of concommitant diseases were treated with benznidazole, which was initiated at
      the same time of the use of corticoid in a group of 12 patients or 15 days
      afterwards in 6 patients. It has been proved in another paper that in the chronic
      phase of Chagas' disease corticoid use is associated with increased parasitemia,
      as evaluated by xenodiagnosis. In this study benznidazole use prevented this
      increase, and we suggest that in immunocompromised patients with chronic Chagas'
      disease the use of this drug could be useful.

PMID- 10881080
TI  - Presence of anti-Toxoplasma antibodies in humans and their cats in the urban zone
      of Guadalajara.
AB  - Cats are the definitive hosts of Toxoplasma gondii. Infected cats excrete oocysts
      in their feces, infecting humans and other animals. The objective of the present
      study was to determine the presence of anti-Toxoplasma antibodies in cat owners
      and their pets, and determine if there was a relationship between Toxoplasma
      infection and humans who live with infected cats. IgG anti-Toxoplasma antibodies
      in sera of 59 cat owners were determined by enzyme-linked immunosorbent assay
      (ELISA), in 24 sera from their cats, IgG, IgM, and IgA antibodies were found
      using Burney's ELISA. Thirty-eight (64%) of 59 cat owners were positive to IgG
      anti-Toxoplasma. Seropositivity for cats was 70.8% IgG, 8.3% IgM, and 62.5% IgA.
      Cohabitation with cats infected by T. gondii, feeding with leftovers or raw
      viscera, and lack of control over how their feces were handled are risk factors
      conducive for humans to become infected by T. gondii.

PMID- 10881081
TI  - [Frequency of diabetes mellitus and hyperglycemia in chagasic and non-chagasic
      women].
AB  - Medical records of > or = 40 years old female seen at University Hospital from
      June/93 to July/95 were submitted to a cross-sectional study. According to
      Chagas' disease tests, patients were divided into chagasic (n = 362) and controls
      (n = 285). Diabetes mellitus was defined on the basis of two fasting blood
      glucose levels > or = 140 mg/dl and hyperglycemia as fasting blood glucose > 110
      mg/dl. Chagasic patients were divided into groups with the cardiac form of the
      disease (n = 179), with megas (n = 58), and asymptomatic (n = 125). Groups were
      compared by the chi 2 test, analysis of variance, Student's "t" test, and Kruskal
      Wallis and Mann-Whitney tests. A significant difference was assumed when p <
      0.05. Chagasic and control groups were matched for age, white color and body mass
      index. Diabetes mellitus was more prevalent in patients with the cardiac form of
      Chagas' disease than in controls, or patients with the megas or the asymptomatic
      form (15.1%, 7.4%, 7.4%, and 5.6%, respectively); the same was observed for
      hyperglycemia (37.4%, 26.7%, 25.9%, 27.2%), in agreement with the hypothesis that
      the reduced parasympathetic activity caused by Trypanosoma cruzi leads to
      relative sympathetic hyperactivity.

PMID- 10881082
TI  - [Outbreak of American cutaneous leishmaniasis in Canoa, Santo Amaro, Bahia,
      Brazil].
AB  - An outbreak of American cutaneous leishmaniasis (ACL) was detected in the village
      of Canoa in 1993. A prospective observational study was outlined to determine the
      frequency rates and to clinically characterize the disease. A total of 555 people
      were followed up. There were 29 cases of ACL, 11 cases of probably previous ACL
      (scars) and 529 healthy individuals. Of these 529 individuals, 65 had a positive
      Montenegro reaction without any present or past evidence of leishmaniasis. The
      prevalence of ACL during the two years was 5.2% (29/555). The leishmania involved
      was Leishmania braziliensis and the vector, Lutzomyia intermedia. Evidence of
      infection was detected in dogs and horses. The high frequency of the disease
      among children under ten years, the similar sex distribution of cases and a
      component of familial aggregation suggest a peri- or intra-domiciliary
      transmission.

PMID- 10881083
TI  - [Cryptococcosis in children in the State of Para, Brazil].
AB  - We report 19 cases of cryptococcosis in children, diagnosed in Belem, PA. In nine
      patients the variety of the etiologic agent was studied and identified as
      Cryptococcus neoformans var. gattii. The average age of these patients was 7.8
      years (range, 5-13 years) There were 5 girls and 4 boys (ratio, 1.25:1).
      Amphotericin B treatment (associated with fluconazole 3 or fluocytosine 1) was
      given but five (56%) of these patients died in the following three months. The
      existence of highly endemic areas of infection by var. gattii in Para, Brazil and
      the severity of the disease due to this fungal variety are commented.

PMID- 10881084
TI  - [Knowledge, attitudes, and practice regarding occupational risk of exposure to
      HIV among medical students at the Medical School of the Federal University of
      Minas Gerais].
AB  - The objectives of this study were to evaluate the occupational risk of medical
      students, their knowledge and practice of universal biosafety measures and
      hepatitis B immunization coverage. A specific questionnaire was applied to 136
      medical students of the Universidade Federal de Minas Gerais: 87 (64%) students
      were involved in surgical procedures, 68 (50%) had been exposed to blood, 90
      (66.2%) knew the universal biosafety measures and 33 (24.3%) knew the procedure
      in case of blood exposure. Thus, this population has a high risk of blood
      exposure and although there is a low formal knowledge about universal biosafety
      measures, most of these were generally used. New strategies, such as formal
      teaching of universal biosafety measures, in loco supervision, and biosafety
      teams, are necessary to change this situation.

PMID- 10881085
TI  - Frequency of myocarditis in cases of fatal meningococcal infection in children:
      observations on 31 cases studied at autopsy.
AB  - The frequency of myocarditis associated with meningococcal disease in children
      was reported only in two autopsied series (United States and South Africa). Here
      we report the frequency of associated myocarditis in 31 children who died of
      meningococcal infection at Hospital Infantile N.S. da Gloria in Vitoria, Espirito
      Santo State, Brazil. The diagnosis was confirmed by isolation of Neisseria
      meningitidis. At least three sections of fragments of both atria and ventricles
      were studied using the Dallas Criteria for the morphologic diagnosis of
      myocarditis. The mean age was 47.6 +/- 39.8 months and the mean survival time
      after the onset of symptoms was 46.1 +/- 26.5 h (12-112 h). Myocarditis was
      present in 13 (41.9%) patients, being of minimal severity in 11 cases and of
      moderate severity in 2 cases. There were no cases with severe diffuse
      myocarditis. The frequency of myocarditis was not influenced by sex, presence of
      meningitis, survival time after the onset of symptoms or use of vasoactive drugs.
      The frequency of myocarditis reported here was intermediate between the values
      reported in the only two case series published in the literature (57% in the
      United States and 27% in South Africa). Although our data confirm the high
      frequency of myocarditis in meningococcal disease, further investigations are
      necessary to elucidate the contribution of myocarditis to myocardial dysfunction
      observed in cases of meningococcal infection in children.

PMID- 10881086
TI  - [American cutaneous leishmaniasis in the Federal District].
AB  - In the present study, we report 11 cases of mucocutaneous leishmaniasis (MCL) in
      patients living in the Federal District who had not left their area of residence
      for a period ranging from six months to two years before the onset of the
      disease. Six of the eleven patients live in the suburban town of Planaltina. All
      showed a positive Leishmanin intradermal reaction. Ten of them presented the
      parasite in their lesions. Leishmania (V) braziliensi was identified in the
      lesions of two patients by the monoclonal antibody method. Nine patients were
      treated with pentavalent antimoy and two with pentamidine. Relapse occurred in
      two cases after treatment with antimony. In view of the detection of vectors and
      infected patients in the Federal District, it is probable that Leishmania
      infection is occurring in Brasilia and its suburban areas.

PMID- 10881087
TI  - [Mefloquine in the treatment of cutaneous leishmaniasis in an endemic area of
      Leishmania (Viannia) braziliensis].
AB  - The aim of this study was to evaluate the efficacy of mefloquine in the treatment
      of skin leishmaniasis in patients infected with Leishmania (Viannia) braziliensis
      at an endemic region. Mefloquine is an oral drug effective against malaria with a
      prolonged half-life, less toxicity and easier administration than pentavalent
      antimonials. At Corte de Pedra in the Southern litoral of Bahia State, two
      randomized groups of ten patients with leishmaniasis were treated. The first
      group was treated with oral mefloquine, 250 mg per day in a single dose for six
      days and repeated three weeks later. The second group received meglumine
      antimoniate (Glucantime), 20 mg/kg daily administered intravenously for 20 days.
      Only one patient in the group treated with mefloquine showed evidence of clinical
      success. During treatment, one patient with four lesions developed a new lesion.
      The other three patients with clinical leismaniasis did not show evidence of
      clinical success after nine weeks of treatment. The group treated with Glucantime
      showed evident clinical improvement of the skin lesions.

PMID- 10881088
TI  - [Immune response produced by anti-rabies vaccines in marmosets (Callithrix sp)].
AB  - In order to evaluate the immune response produced by rabies vaccines in new world
      nonhuman primates, thirty marmosets (Callithrix sp) were divided into five groups
      of six individuals and submitted to five different antirabies vaccination schemes
      using two distinct commercially available animal vaccines. The first was produced
      in suckling mouse brain (Fuenzalida and Palacios), and the second in NIL-2 cell
      culture. Post-vaccine serological monitoring was carried out periodically. The
      results showed that the Fuenzalida and Palacios vaccine was not able to protect
      the animals when using a single dose or even with a booster. But when submitted
      to a vaccination routine similar to that used for humans, the marmosets showed
      detectable antibodies, and only one succumbed to rabies after being challenged.
      In addition, the vaccine produced in NIL-2 cell culture induced high antibody
      levels in all vaccinated animals and all animals survived the viral challenge.

PMID- 10881089
TI  - [Epidemiology of sporotrichosis in the central region of Rio Grande do Sul].
AB  - Thirty-one cases of sporotrichosis diagnosed in the central region of Rio Grande
      do Sul from 1988 to 1997 were studied. Clinical data were compared with a study
      concerning three past decades, clearly showing a decrease in the incidence of the
      mycosis, and an alteration in the profile of the infection, with a decrease of
      sporotrichosis in rural patients, children, women and farmers. In the past decade
      the mycosis was most frequent among urban adults with different professions, with
      the onset of the disease being associated with rural leisure activities such as
      fishing and hunting.

PMID- 10881090
TI  - [Correlation between sanitation conditions and intestinal parasitosis in the
      population of Assis, State of Sao Paulo].
AB  - The distribution of the most frequent enteroparasites in the population of Assis,
      State of Sao Paulo, was studied from 1990 to 1992. A total of 18,366 medical
      examinations from six sanitary care centers in the neighbourhoods of Marialves,
      Progresso, city center, Xavier, Fiuza and Bonfim were analyzed. The general
      prevalence of enteroparasites was 23.3%. The most frequently found
      enteroparasites were: Giardia intestinalis (8.7%), Ascaris lumbricoides (5.5%),
      Trichuris trichiura (2.4%) and Hymenolepis nana (1.9%). In Marialves, a low
      income neighborhood, the prevalences were: 17%; 13.1%; 5.9% and 4.2%,
      respectively. The age group from 3 to 12 years showed the largest number of
      infected individuals. There was a correlation between basic sanitation
      conditions, expressed as the number of places connected to the city water and
      sewage systems, and the prevalence of parasites. There was also a decrease of
      parasite prevalence in all sanitary care centers from 1990 to 1992, which
      coincided with the increase in the number of new water and sewage systems in
      these neighborhoods.

PMID- 10881091
TI  - [Children with acute respiratory distress syndrome: anatomoclinical and
      radiologic correlation].
AB  - This retrospective study reviews cases of ARDS (Adult Respiratory Distress
      Syndrome) treated and followed up from October 1988 to December 1990 in the
      Pediatric Intensive Care Unit of Instituto Fernandes Figueira/FIOCRUZ, Brazil.
      Clinical, radiological and histopathological features were analyzed and
      correlated with well defined stages of the disease process. Out of 459 cases, 49
      (11%) were selected for further study. In 11 cases, histopathological examination
      (4 biopsies and 8 autopsies) was performed and then classified into one of the
      following phases: exsudative, cellular proliferative and late fibrotic. The work
      emphasizes the need for further clinical and experimental studies in order to
      define the mechanisms and the impact of this Syndrome in the pediatric
      population.

PMID- 10881092
TI  - [Paracoccidioidomycosis in Brazilian Indians of the Surui tribe: clinical
      laboratory study of 2 cases].
AB  - Paracoccidioidomycosis has been considered the most frequent endemic systemic
      mycosis in Latin America. Although most cases of paracoccidioidomycosis involve
      rural workers, this systemic fungal disease has been scarcely reported among
      Amerindian populations from Brazil. We report two cases of paracoccidioidomycosis
      in Tupi-Monde Amerindians from Cacoal, state of Rondonia, Brazil. Both cases
      exhibited positive serological results by a specific immunodiffusion test only
      when the assay was performed with antigens obtained from the mycelial form of P.
      brasiliensis. The authors present a literature review of paracoccidioidomycosis
      in Brazilian Amerindians and discuss the need for further investigations about
      the impact of the antigenic diversity of P. brasiliensis from different
      geographic areas on the serological diagnosis of PCM.

PMID- 10881093
TI  - [Detection of hepatitis C virus antibodies in a pool of 5 sera: their use in
      seroepidemiologic studies].
AB  - In order to evaluate the reduction in the cost of testing for antibodies against
      hepatitis C (EIA) by the pool method, we tested serum samples from a rural
      population and from patients in a hemodialysis program. Two thirds of the high
      risk groups were positive. Pooling reduced the reagent use by 80% in the rural
      population and by 13% in the hemodialysis patients. We conclude that pool testing
      reduces the cost of anti-HCV detection in low-risk groups.

PMID- 10881094
TI  - [Contamination of public squares of Campo Grande, Mato Grosso do Sul, Brazil,
      with eggs of Toxocara and Ancylostoma in dog feces].
AB  - From February to October 1998, the contamination of public squares of Campo
      Grande, MS, Brazil, by eggs of Toxocara and Ancylostoma was evaluated in dog
      fecal samples. Out of the 74 public parks examined, 42 (56.8%) were found to be
      contaminated with Ancylostoma eggs, 8 (10.8%) with Toxocara eggs and 7 (9.5%)
      with both.

PMID- 10881095
TI  - Mefloquine in the treatment of cutaneous leishmaniasis.
AB  - Three cases of cutaneous leishmaniasis were treated orally with a mefloquine dose
      of 4.2 mg/kg/day for six days in the Teaching Hospital of the Faculdade de
      Medicina do Triangulo Mineiro, Uberaba, MG, Brazil. Three weeks later a new
      series was repeated. No patient was cured.

PMID- 10881096
TI  - [Diagnostic of congenital syphilis: a comparison between serological tests in
      mothers and their newborns].
AB  - For the purpose of establishing the incidence of maternal and congenital syphilis
      among pregnant women at delivery and their respective newborns, a study was
      carried out to determine treponemic and non-treponemic serology in one thousand
      (1,000) parturient women and their children at Santa Marcelina Hospital - Sao
      Paulo, between June 95 and July 96. All blood samples (maternal venous, umbilical
      cord and newborn venous) were VDRL-tested, treponemic tests (TPHA, ELISA IgG,
      ELISA IgM) being applied whenever one of the samples from mother or newborn
      proved positive. Further, an anti-HIV search was run through ELISA among VDRL
      positive mothers. Among the 1,000 parturients, 24 (2.4%) were found to be VDRL
      reactive; 18 (1.8%) newborn children of these 24 mothers presented positive
      serology in their umbilical cord blood and 19 (1.9%) in venous blood. No positive
      newborns were found for negative mothers. From the high occurrence of maternal
      and congenital syphilis in this group of patients, we propose a VDRL maternal
      test as a way of selecting gestational and congenital syphilis cases, since this
      test appeared to be sufficiently capable of such diagnoses. Of the treponemic
      tests, the ELISA test did not enhance diagnostic sensitivity.

PMID- 10881097
TI  - Report on ticks collected in the Southeast and Mid-West regions of Brazil:
      analyzing the potential transmission of tick-borne pathogens to man.
AB  - Specimens of ticks were collected in 1993, 1996, 1997, and 1998, mostly from wild
      and domestic animals in the Southeast and Mid-West regions of Brazil. Nine
      species of Amblyommidae were identified: Anocentor nitens, Amblyomma cajennense,
      Amblyomma ovale, Amblyomma fulvum, Amblyomma striatum, Amblyomma rotundatum,
      Boophilus microplus, Boophilus annulatus, and Rhipicephalus sanguineus. The
      potential of these tick species as transmitters of pathogens to man was analyzed.
      A Flaviviridade Flavivirus was isolated from Amblyomma cajennense specimens
      collected from a sick capybara (Hydrochaeris hydrochaeris). Amblyomma cajennense
      is the main transmitter of Rickettsia rickettsii (=R. rickettsi), the causative
      agent of spotted fever in Brazil. Wild mammals, mainly capybaras and deer,
      infested by ticks and living in close contact with cattle, horses and dogs, offer
      the risk of transmission of wild zoonosis to these domestic animals and to man.

PMID- 10881098
TI  - [Long-term follow up of asymptomatic chagasic individuals with intraventricular
      conduction disturbances, correlating with non-chagasic patients].
AB  - This prospective study was designed to evaluate intraventricular conduction
      disturbances in asymptomatic patients with Chagas' disease, and patients with
      primary sclerosis of the conducting system of the heart (Lev-Lenegre's disease).
      Eighty-four asymptomatic individuals with right- or left-bundle branch block were
      submitted to electrophysiological evaluation and long-term follow-up. Fifty-five
      had positive serologic blood tests for Chagas' disease and 29 had Lev-Lenegre's
      disease. Mean-age of 45 years in chagasic and 63 in non-chagasic patients (p<
      0.001). There were 54 (98.2%) with right-bundle branch block in chagasic and 14
      (48.3%) among non-chagasic patients (p <0.001). Sinus nodal and atrioventricular
      nodal functions presented no differences in either group. However, mean HV
      interval was greater in the NCH than in the CH group (p< 0.01). After a mean
      follow-up of 121 +/- 63.75 months among chagasic and 94.97 +/- 67.55 months among
      non-chagasic patients, total mortality was 20 (36.6%) patients in chagasic and 9
      (31%) among non-chagasic patients (NS). Cardiac death was recorded in 17 (85%)
      individuals among chagasic and 3 (33.3%) among non-chagasic patients(p <0.05).
      Sudden death occurred in 10 (50%) among chagasic and was not observed in non
      chagasic patients (p <0. 01). IN CONCLUSION: 1. Asymptomatic chagasic individuals
      with intraventricular conduction disturbances showed higher cardiac mortality,
      sudden or non-sudden death in relation to non-chagasic individuals. 2. The
      evaluated electrophysiological parameters were of no prognostic value in relation
      to mortality, although programmed ventricular stimulation was not performed.

PMID- 10881099
TI  - [Congenital Chagas-Mazza disease in Salta, Argentina].
AB  - A study was carried out on T. cruzi infection in pregnant women in the Guemes
      area in Salta province; the rate of infection was 12.3%. Of newborn children
      studied by the microhematocrit technique, 8.8% were diagnosed with Chagas'
      disease. All of them were treated with benznidazol (5mg/kg/day) for one month;
      all of them presented anemia, which was interpreted to be an adverse drug
      reaction. The microhematocrit technique is believed to represent the best option
      for diagnosis of this disease in newborn children. A diagnostic methodology to
      follow the course of the infection is proposed.

PMID- 10881100
TI  - [Epidemiological and clinical aspects of snake bites in the municipalities of the
      state of Amazonas, Brazil].
AB  - In the State of Amazonas, accidents with snakes are a public health problem. For
      this reasons, the objective of this work was to carry out a descriptive study of
      the snake accidents attended in the health units of 34 municipalities, one
      district and two border platoons in the State of Amazonas. The characteristics
      most commonly observed among those involved in snake accidents were: farmers (50.
      4%), male (81.3%), belonging to the working age-group (72.1%), bitten on an upper
      limb (88.5%) by a "jararaca" (48.6%) or a "surucucu" (46.8%) in the rural part of
      the municipality (70.2%). The local signs and symptoms most frequently observed
      in those who received medical care more than 6 hours after the accident (57.3%)
      were edema (76.9%), pain (68.7%), erithema (10.2%) and hemorrhage (9. 3%). The
      systemic manifestation most frequently observed was hemorrhage (18.8%).
      Serotherapy was administered in only 65.9% of patients, the intravenous route
      being the route most commonly used to administer the antivenin (52.3%), while
      other non- recommended routes were widely used. In the majority of patients the
      antivenin given was antibotropic. The most frequent complications were: abscess
      13.7%, necrosis 12.3%, secondary infection 8.3%, renal insufficiency 2.5% and
      gangrene 2.5%. The medical procedures most used in the treatment of these
      complications were drainage 52.6%, debridement 28.9%, amputation 10.5%, surgical
      cleaning 5.3% and peritoneal dialysis 2.6%. The fatality rate was 1%.

PMID- 10881101
TI  - [Helminth eggs and larvae in restrooms at municipal nursery schools in Sorocaba,
      SP, Brazil, and their frequency in children feces].
AB  - The purpose of this research was to establish a relationship between the presence
      of helminth eggs in the water closet elements and the frequency of these eggs in
      the feces of their users. 1050 kindergarten children's feces were examined by the
      spontaneous sedimentation method in three samples of feces, which were positive
      in 162 children presenting 184 eggs or helmints larvs. From the 465 water closet
      elements, constituted of : toilet seat, internal and external door knobs, latch,
      faucet handle and discharge valve, of 12 Infant Educational Centers of Sorocaba,
      examined by sticking some transparent adhesive tape on microscopy slides, were
      found 18 eggs of Ascaris lumbricoides; 1 of Enterobius vermicularis and 4 larvs
      of nemathoids partially deformed were found in 23 infected elements. There wasn't
      significance relationship between the elements of water closets and user's feces
      contamination.

PMID- 10881102
TI  - [Chagas' disease in Sao Paulo State: a comparative study between systematic
      search and inhabitants' report of bugs in the area under entomological
      surveillance].
AB  - Entomological surveillance of Chagas' disease in Sao Paulo State has adopted a
      scheme that uses the locality as a unit for field work. Actions are prioritized
      according to infestation levels obtained by systematic search of triatomine
      (routine actions), bugs in areas with high infestation levels and in houses whose
      inhabitants report the presence of the bugs (reply to notification). The most
      prevalent triatominic species in Sao Paulo State at present are Triatoma sordida
      and Panstrongylus megistus. A comparative study of infestation levels obtained in
      houses and surroundings in routine search and replies to notification in the two
      year periods of 90/91, 92/93 and 94/95, has shown average percentage positivity
      of 1.3 indoors in routine activity and 6.2 in the reply to notification. For the
      house surroundings the values were 8.6 and 18.2 respectively, no differences
      being found between the two-year periods. Replies to notification showed average
      percentage positivity (focus) in 26% of the houses. It was verified that the
      notifications had come from localities with prior infestation levels equal to
      zero (I = O), intermediary infestation levels (I < 5) and high infestation levels
      (I > 5), although the percentages of positive replies to notification were higher
      in those localities with high prior infestation levels. These results reinforce
      the importance of notification in the surveillance of vector species of the
      invasive type like those currently prevalent in Sao Paulo State.

PMID- 10881103
TI  - [Standardization of enzyme-linked immunosorbent assay ELISA to detect anti
      Toxoplasma gondii IgM and IgG antibodies, and comparison with the indirect
      immunofluorescence technique].
AB  - Serology has been the most popular method to diagnose toxoplasmosis. Accordingly,
      this study standardizes an enzyme-linked immunosorbent assay (ELISA) and compares
      its results with the IFI technique. In the IgG detection test, the standardized
      technique presented a sensibility (S) of 96.77%, a specificity (SP) of 75%, with
      a positive predictive value (PPV) of 83.33%, a negative predictive value (NPV) of
      94.74%, and an adjusted concordance (K) of 73.50%. The IFI exhibited 83.87% for
      S, 79.16% for SP, 83.81% for PPV, 79. 16% for NPV, and 63% for K. The rough
      concordance between these two tests (ELISA/IFI) was 88.35% for the IgG detection
      test and 81.55% for the IgM detection test. K was 70.82% and 1.31% for IgG and
      IgM, respectively, the correlation index (r) being 0.556 for IgG and -0. 023 for
      IgM. We can conclude that standardized ELISA-IgG is indicated in serologic
      selection processes, whereas the ELISA-IgM is not recommended for presenting low
      values for the adjusted concordance with the reference technique, which suggests
      not very reliable results.

PMID- 10881104
TI  - [Seroepidemiology of toxoplasmosis and ocular evaluation by Amsler grid in
      patients from the rural area treated at the Jaguapita county health center,
      Parana State, Brazil].
AB  - In this study, we collected serum from 82 randomly selected patients from a rural
      area in Jaguapita county, Parana State. All sera were subjected to indirect
      immunofluorescence assay (IFA) to detect IgG antibodies against T. gondii. Serum
      titers >/=+ 16 were considered positive. Of the 82 evaluated sera, 68 (82.9%)
      were positive to toxoplasmosis and 14 (17.1%) were non-reactive. The most common
      titers found were 64 (23/33.8%) and 256 (16/23.5%), the highest titer being 4096
      (8/11.8%). The 82 patients were also evaluated by the Amsler Grid test, with 22
      (26.8%) patients presenting at least one alteration in this test. Masculinity was
      found to be a protection factor in the Amsler grid test (OR = 0.21 0.04 < OR < 0.
      86 chi2 = 4,98 p = 0,02). There were no significant statistical differences
      related to the epidemiological investigation. We concluded that T. gondii has a
      wide distribution in the population studied.

PMID- 10881105
TI  - [Compatibility between nine strains of Biomphalaria glabrata coming from endemic
      and non-endemic areas and one strain of Schistosoma mansoni from Venezuela].
AB  - Nine lots of 32 B. glabrata snails (5-7mm in diameter) from the following strains
      from the endemic area: Cagua, Valencia Lake (Puerta Negra Sector), Ingenio
      Bolivar (Aragua State), Mariara, Caserio El 25 and Guigue (Carabobo state), and
      from the non-endemic area: Anzoategui (Lara state), Chabasquen (Portuguesa state)
      and Caripe (Monagas state) were experimentally infected (5 miracidiums/snail)
      with C5 Schistosoma mansoni strain. The intramolluscal prepatent period
      oscillated between 23 and 25 days for the nine strains. The duration of
      intramolluscal infection varied a lot, from 20 days in the case of the Chabasquen
      strain to 93 days for the Guigue strain. The average cercariae production in the
      3rd day of emission varied from X = 74.4 for the Mariara strain to 591.7 in the
      case of the Chabasquen strain. Significant statistical differences were found in
      relation to the total number of emitted cercariae in the 3rd day (H = 97.4; P <
      0.05), with significant statistical differences detected among most of the 36
      strain combinations, except for the following: Mariara/Ingenio Bolivar,
      Cagua/Cas. El 25, Valencia Lake/Guigue and Guigue/Caripe. The strains of Valencia
      Lake (88.8%), Cagua (85.2), Chabasquen (82.6%) and Caripe (82.6%) showed the
      highest rates of self-cure, whereas the Guigue strain showed the lowest: 21.4%.

PMID- 10881106
TI  - Cerebrospinal fluid syndromes in HIV-positive patients with acute consciousness
      compromise.
AB  - We reviewed the cerebrospinal fluid (CSF) syndromes of 100 consecutive HIV
      positive patients presenting acute consciousness compromise in emergency rooms,
      and correlated them with clinical data. The most frequent CSF syndromes were:
      absolute protein-cytological dissociation (21), viral (19), neurocryptococcosis
      (7), relative protein-cytological dissociation (6) and septic (4), moderate
      hypoglycorrachia (4), severe hypoglycorrachia (4) and hydroelectrolytic
      disturbance (3). One fifth of the patients had CSF syndromes considered
      sufficient for diagnosis or an immediate clinical decision. The most common
      clinical data were infective and neurological. There was little correlation
      between the clinical data and the CSF syndromes. We conclude that in HIV-positive
      individuals presenting acute consciousness disturbances there are frequently non
      specific results in the CSF analysis that must be weighed against a detailed
      history and thorough physical examination. Taking this into account, in about one
      fifth of cases the CSF analysis can offer useful information for treatment.

PMID- 10881107
TI  - [Congenital Chagas' disease in the province of Salta, Argentina, from 1980 to
      1997].
AB  - This is the experience of 18 years of attending newborn infants suffering from
      congenital Chagas' disease. From a variety of sources in the provincial health
      system, the Mother-Child Hospital in the city of Salta, country hospitals and out
      patient care, 102 newborn and infants were detected and diagnosed. The newborn
      were classified into two main groups, one being sub-classified according to
      diagnostic opportunity. The diagnostic methodology, clinical presentation,
      treatment and follow-up of the children under care are described, the
      characteristics of the experience analyzed and the specific conditions of the
      diagnostic discussed. Also described are the recommendations used in the province
      in the perinatal Chagas control program, as well as the conclusions reached by
      this experience.

PMID- 10881108
TI  - [Giardiasis and helminthiasis in children of both public and private day-care
      centers and junior and high schools in the city of Mirassol, Sao Paulo State,
      Brazil].
AB  - This study showed different frequencies of intestinal parasitosis (giardiasis and
      helminthiasis) among children in day-care centers and junior and high schools
      (public and private). The survey involved 199 individuals, 96 belonging to public
      schools and 103 to private institutions. The frequency of giardiasis in public
      institutions was shown to be greater than in private institutions. Regarding
      helminthiasis, frequencies were similar among day-care centers, but greater for
      public schools in comparison to private institutions. When levels of socio
      economic status, education, basic sanitary conditions and hygiene were analyzed
      as determinants of intestinal parasitosis, it became evident that greater
      frequency of giardiasis and helminthiasis occurred among children from low-income
      families and those whose parents had low levels of education. The source of
      vegetables was also a significant factor in determining such parasitosis.

PMID- 10881109
TI  - [Problems in the development of a vaccine against schistosomiasis mansoni].
AB  - During the last two decades, studies on antigens that may confer protective
      immunity to experimental infection with Schistosoma mansoni have made great
      advances, due largely to increased knowledge in the fields of molecular biology
      and immunology. Although these studies have made new and important contributions,
      at the present time the degree of protection conferred remains at approximately
      50% in reducing the number of flukes and, with some antigens, the number of eggs.
      The many questions still to be answered indicate the necessity of carrying out
      further research on small and large animals before these antigen candidates for
      vaccines can be used in clinical tests.

PMID- 10881110
TI  - [Concurrent leishmaniasis and human immunodeficiency virus (HIV) infection: a
      study of four cases].
AB  - Few cases of concurrent leishmaniasis and HIV infection have been reported in
      Brazil, despite both infections being in expansion. Two cases of visceral
      leishmaniasis and two cases of mucocutaneous leishmaniasis are discussed.
      Disseminated skin and oral lesions were found in the patients with the cutaneous
      form of the disease. Prolonged fever, hepatosplenomegaly and pancytopenia were
      the main manifestations of the visceral form. The CD4 T lymphocyte count was low
      in all cases. Direct examination of bone marrow aspirate for leishmania and
      biopsy of cutaneous lesions are the techniques of choice to confirm diagnosis.
      Pentavalent antimonials and amphotericin B are preferred drugs for the treatment
      of leishmaniasis, including patients with AIDS. The authors recommend the
      inclusion of this parasitosis in the differential diagnosis of opportunistic
      diseases in patients with AIDS.

PMID- 10881111
TI  - [Sand-fly fauna (Diptera, psychodidae, phlebotominae) in Bolivar State,
      Venezuela].
AB  - A descriptive study is presented of sand-fly fauna in Bolivar State, Venezuela.
      Identification was made of 2,364 sand-flies belonging to 18 species. The vectors
      of American cutaneous leishmaniasis in the different geographic regions of
      Bolivar State are possibly L. anduzei, L. wellcomei and L. squamiventris in the
      South, and L. flaviscutellata and L. gomezi in the North.

PMID- 10881112
TI  - [Hepatitis A and hepatitis B seroprevalence in 4 centers in Brazil].
AB  - The prevalence of antibodies to hepatitis A and B virus was assessed in 3,653
      subjects across four regions of Brazil. The anti-HAV and anti-HBc seroprevalence
      were 64.7% and 7.9%, respectively. The highest anti-HAV (92.8%) and anti-HBc
      (21.4%) rates were seen in the Northern region. In other regions, anti-HAV
      seroprevalence over 90% was only reached in the more elderly, indicating an
      intermediate endemicity and a significantly higher anti-HAV prevalence was seen
      in the low socioeconomic group between 1-30 years. With respect to anti-HBc
      seroprevalence an increase was seen in adolescents and there was a significantly
      higher anti-HBc prevalence in the lower socioeconomic group between 1-20 years. A
      3.1% anti-HBc prevalence was seen in one-year-old infants, suggesting a vertical
      transmission. The major findings of this study indicate that the pre-adolescent
      and adolescent population in some Brazilian cities are at greatest risk from both
      hepatitis A and B infection, but for different reasons.

PMID- 10881113
TI  - [Phlebotominae (Diptera: Psychodidae) of Lagoas, a city of Buriticupu, Amazonia
      of Maranhao. I. The richness and relative abundance of the species in an area of
      recent colonization].
AB  - In this study the diversity of the species and relative abundance of the sand
      flies in the Amazonian community of Lagoas, in Buriticupu, Maranhao State, was
      determined. The study consisted of adult sandflies captured with CD light-traps,
      Shannon-trap and manual aspiration tube, between 18 PM and 6 AM, once a month,
      from December/95 to January/97, in a forest fragment and in the domestic
      environment (peri and intra). In all, 9,393 specimens were captured (4,302 males
      and 5,140 females) distributed among 38 species (1 Brumptomyia and 37 Lutzomyia).
      The diversity and abundance of species was higher in the forest, followed by the
      peri and intra. The predominance in the wild ambient is a consequence of the
      potentialities found in the remaining fragments of the forest which have survived
      the lumber yard exploitation and agricultural activities. In the forest
      environment Lutzomyia whitmani (64.9%), L. migonei (27%) and L. serrana (3.6%)
      were the most frequent species. In the peri and intra domicile L. evandroi
      predominated (55.4% and 97.9%). The species, L. whitmani (33.4%) and L. migonei
      (6.4%), were important in the peri domicile. The peridomestic habit of 7.7% of
      the sand flies showed the greatest epidemiologic importance, due to the existence
      of patients with leishmaniasis ulcers, who believe they were infected near their
      habitations.

PMID- 10881114
TI  - [The clinical laboratory characteristics of 104 cases of cryptococcal
      meningoencephalitis].
AB  - With the purpose of describing the clinical and laboratory characteristics of
      cryptococcus meningoencephalitis, we reviewed the records of 104 patients
      admitted with this diagnosis at Couto Maia Hospital, reference for patients with
      infectious diseases in Salvador-BA Northeastern Brazil, from 1972 to 1996. The
      patients' age varied from 8 months to 79 years. Sixty-four (61.5%) patients were
      male. The duration of the disease varied from 2 to 150 days, average 27.7 days.
      The most common signs and symptoms were headache (92.7%), fever (84.4%) and neck
      stiffness (83.2%). The cell number in cerebrospinal fluid was greater than 4/mm >
      or = in 95.8% of the patients with lymphocyte predominance in 86.3% of the cases.
      The lethality rate was 42.7%.

PMID- 10881115
TI  - Prevalence of HIV-1/2, HTLV-I/II, hepatitis B virus (HBV), hepatitis C virus
      (HCV), Treponema pallidum and Trypanosoma cruzi among prison inmates at Manhuacu,
      Minas Gerais State, Brazil.
AB  - The purpose of this study was to determine the seroprevalence of human
      immunodeficiency virus (HIV-(1/2)), human T-cell lymphotropic virus (HTLV-I/II),
      hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum and
      Trypanosoma cruzi among 63 male prisoners in Manhuacu, Minas Gerais, Brazil and
      to compare this with data from eligible blood donors. The positive results were
      as follows: 11/63 (17.5%) for HBV, 5/63 (7.4%) for syphilis, 4/63 (6.3%) for HCV,
      3/63 (4.8%) for Chagas' disease, 2/63 (3.2%) for HIV-1/2 and 1/63 (1.6%) for HTLV
      I/II. The seroprevalence in prisoners was higher than among blood donors, mainly
      for antibodies to HIV-1/2, HCV and HBV. This is probably due to low social
      economic level, illiteracy, higher proportion with a prior history of intravenous
      drug use and/or unsafe sexual behavior. Therefore, these prisoners constitute a
      high-risk group and routine screening and counseling are recommended.

PMID- 10881116
TI  - [An evaluation of an outbreak of American cutaneous leishmaniasis in a rural
      community in Bolivar State, Venezuela].
AB  - An epidemiological survey based on the Montenegro intradermal reaction (IDR) was
      carried out in San Jose de Hacha, south of the Bolivar State, Venezuela, on the
      occasion of an outbreak of American tegumentary leishmaniasis (LTA) in that
      locality. The IDR was applied to 121 of the 184 local inhabitants (65.8%), with a
      33.9 rate of positive reactions (44/121). The highest percentage of positivity
      was observed among males (39.5%) (P < 0.05) and among adults, especially in the
      31 to 40 year age group (52.4%) (chi2 = 18.28; g.l. = 6). With respect to
      occupation, agriculturist were the most reactive with 69%. of subjects IDR
      positive, in 65.9% (27/41) the reaction areas ranging from 5 to 9 mm. Active
      lesions of LTA were identified in 22 inhabitants and scars were detected in only
      seven cases. It is suggested that San Jose de Hacha is a recent focus of LTA.

PMID- 10881117
TI  - [The immune state against yellow fever vaccinal virus (17D) in 2 populations of
      Bahia State, Brazil].
AB  - The occurrence of cases of yellow fever (YF) and also the extensive distribution
      of A. aegypti in Brazil, inspired a study about the estimate of immunity against
      vaccinal virus (17D) among the residents at two cities of the Bahia State,
      Ipupiara (n = 461) and Prado (n = 228). At this non-endemic area of YF, the
      search for serology antibody against 17D (Ab17D) and 18 another arbovirus was
      made thereby hemagglutination inhibition (HI). Only 1.2% (8/689) showed Ab17D,
      six of those with monotypic sort. The heterotypic sort for flavivirus (FLV) was
      interpreted as associated to immunity against 17D too, being much frequent in
      Prado (30.3%) than in Ipupiara (23.2%). The age > or = 50 years and residence in
      another states were related to seropositive for FLV, the same way that
      vaccination's history (17D). However, the history of vaccination presented low
      percentages of sensibility (< or = 45.4%) and predictive-positive value (< or =
      38.4%), but high specificity (> or = 70.8%) and predictive-negative value (> or =
      78.8%). Therefore, the frequency of residents with Ab17D was low (1.2%), although
      the higher frequency (25.5%) of antibody FLV carrier's, what signifies that 26.7%
      of the studied population should present protection against the YF virus.

PMID- 10881118
TI  - [Sexually transmitted diseases in patients infected with HIV/AIDS in the State of
      Pernambuco, Brazil].
AB  - The data was obtained retrospectively from clinical records concerning 399 HIV
      infected patients. The HIV infected individuals predominated in the age group
      ranging from 20 to 40 years (73.4%) and 75% were male. The was no difference in
      the ratio of male and female patients regarding asymptomatic HIV infection or
      AIDS. The cases of HIV without AIDS concentrated in the age group ranging from 20
      29 years while AIDS predominated in the age group ranging from 30-39 years. Only
      0.8% were hemophilic, 3.5% injected drugs and 4.8% had hemotransfusions in the
      last 5 years. Regarding sexual behavior, 33% were heterosexuals, 11% bisexuals,
      23% homosexuals and 33% did not disclose their sexual behavior. The presence of
      syphilis was the most frequent combination found (8.8%), followed by herpes
      (5.8%) and genital candidiasis (4.3%). Our results suggest an association between
      genital candidiasis and AIDS, although this was not demonstrated for the other
      STDs studied.

PMID- 10881119
TI  - [Malaria in the region of Campinas, Sao Paulo, Brazil, 1980 to 1994].
AB  - According to epidemiological data, from 1980 to 1994, 2,781 cases of malaria were
      registered as follows: DIR XII-Campinas (49.3%), DIR XV-Piracicaba (41.3%) and
      DIR XX-Sao Joao da Boa Vista (9.4%). The Plasmodium vivax was found in 70.6% of
      the patients; Plasmodium falciparum in 25.4% and 4% of the patients presented a
      mixed infection. The epidemiological classification showed that 95% of the cases
      came from the States of Rondonia, Mato Grosso and Par. The masculine sex, between
      the age of 20 to 39 years old, was responsible for 84.3% of the confirmed cases.
      During the study period, 9 cases of induced malaria were registered: 5 of which
      through blood transfusion, 3 through the sharing of syringes and infected needles
      among drug users and one occurrence of congenital malaria. 5 deaths were
      registered in patients prime-infected by Plasmodium falciparum with late
      diagnosis. The set of variables studied enabled a greater understanding of the
      epidemiology of malaria in the region and to subsidize and indicate the process
      of decentralization of attendance, diagnosis and treatment of the patient, as
      well as the control and epidemiological surveillance of the endemic disease in
      Campinas region and in the State of Sao Paulo.

PMID- 10881120
TI  - [A dengue epidemic in Ipupiara and Prado, Bahia. A seroepidemiologic survey].
AB  - Serologic studies in Brazil have indicated a 25% to 56% prevalence of dengue
      virus infections. However, these studies were carried out in populations of
      middle-sized and larger cities. The present study describes two epidemics of
      classic dengue fever in two small cities in the State of Bahia. The first
      occurred in 1987, in Ipupiara and was caused by dengue serotype-1 (DEN-1), the
      second occurred in 1995, in Prado and was caused by dengue serotype-2 (DEN-2).
      The laboratory diagnosis was made by the hemagglutination-inhibition test. 461
      serum samples were collected in 1995 in Ipupiara (district of Chapada Diamantina)
      out of a population of 3,868 and 228 samples out of a total of 9,126 inhabitants
      of Prado (in the southernmost coastal region). The seropositivity of the samples
      was 11.9% (55/461) in Ipupiara and 17.5% (40/228) in Prado. These were no
      statistically significant differences as to age and sex between seropositive and
      seronegative individuals of the two cities studied. However, the seropositive
      cases in Ipupiara indicated a higher percentage (15.9% vs. 9.3%) of residency in
      or travel to other states of Brazil (p<0.03). Based on these data we estimate the
      occurrence of 460 and 1,597 cases of infection in Ipupiara and Prado,
      respectively. In conclusion, dengue virus infections in smaller cities probably
      have singular characteristics, since they exhibit a lesser prevalence of
      seropositivity caused by decreased breeding possibilities of Aedes aegypti.

PMID- 10881121
TI  - Control of intestinal helminths in schoolchildren in Low-Napo, Ecuador: impact of
      a two-year chemotherapy program.
AB  - A school-based control program of intestinal helminths was undertaken among
      schoolchildren in the Low-Napo region, north-eastern Ecuador. Forty-eight percent
      of children were infected with one or more helminths at the first examination.
      The prevalence at the baseline was Ascaris 33.2% followed by hookworm 24.1% and
      Trichuris 6.5%. Sex was found to be a significant factor influencing the
      prevalence of hookworm and Trichuris. Prevalence was compared 9 months and 18
      months after treatment. After 9 months, Ascaris and Trichuris prevalence had
      decreased but not hookworm. All of them increased after 18 months. The findings
      suggest that only a course of mebendazol had a minor effect on the control of
      helminth infections.

PMID- 10881122
TI  - [Cryptococcus neoformans isolated from patients with AIDS].
AB  - Cryptococcosis is considered the most frequent fungal systemic opportunist
      infection in patients with AIDS. C. neoformans var. neoformans infects the
      patients with AIDS more often than C. neoformans var. gattii which has been
      rarely isolated from patients with AIDS. Even in endemic regions of C. neoformans
      var. gattii, the variety of neoformans is still the most common agent diagnosed
      in cryptococcosis of patients with AIDS. Cerebrospinal fluid (CSF) from fifty
      patients with neurocryptococcosis associated with AIDS were studied. The fungi
      were isolated in agar Sabouraud medium, and were identified by microscopic and
      macroscopic examination by agar Sabouraud, agar niger and Christensen's urea
      medium. The variety was determined based on a color characteristic reaction on
      glycine-L-canavanina-bromothymol blue agar. From all of the fifty patients'
      cerebrospinal fluid (CSF) we were able to recover C. neoformans. The isolates
      were identified as C. neoformans var. neoformans in 47 patients and as C.
      neoformans var. gattii. in the 3 remaining patients. These findings suggest that
      both varieties, gattii and neoformans, are agents of neurocryptococcosis in
      patients with AIDS.

PMID- 10881123
TI  - Confocal fluorescence microscopy: a powerful tool in the study of Chagas'
      disease.
AB  - Confocal scanning fluorescence microscopy has become widely used in cell biology
      and pathology. In conjunction with monoclonal antibodies it may turn out to be a
      powerful diagnostic tool that also enables detailed studies of tissue forms of
      Trypanosoma cruzi.

PMID- 10881124
TI  - [Benznidazole in the primary chemoprophylaxis of the reactivation of Chagas'
      disease in chronic chagasic patients using corticosteroids at immunosuppressive
      doses: is there sufficient evidence for recommending its use?].
AB  - There is evidence that trypanosomicide drugs prevent the parasitological
      reactivation of Chagas' disease in patients under corticosteroid therapy. On the
      other hand there are few reports of clinical reactivation of this disease
      associated with the use of these immunosuppressive drugs. Primary
      chemoprophylaxis with trypanosomicide in this situation should not be recommended
      before being assessed by a randomized controlled trial.

PMID- 10881125
TI  - [A case report of human lagochilascariasis coming from Para State, Brazil].
AB  - A new case of lagochilascariasis is reported in a child from Xinguara, PA,
      Brazil. The patient had an abscess in the right cervical region, which was
      drained at the Clinical Hospital of UFG. Eggs and adult stages of Lagochilascaris
      minor were found in the secretion of the abscess. Treatment with albendazol, at a
      dosage of 400 mg/day for 30 days, associated with antibiotics promoted regression
      of the lesion.

PMID- 10881126
TI  - [Notes on fleas (Siphonaptera) of the fox Cerdocyon thous (Canidae) from an
      endemic area of visceral leishmaniasis in Jacobina, Bahia, Brazil].
AB  - From July to September of 1998, 152 fleas were collected from 18 specimens of the
      fox Cerdocyon thous captured in the visceral leishmaniasis endemic area of
      Jacobina, State of Bahia, Brazil. The fleas were identified as: 136
      Rhopalopsyllus lutzi lutzi, 11 Pulex irritans, 2 Ctenocephalides canis, 1
      Ctenocephalides felis felis and 2 Xenopsylla cheopis.

PMID- 10881127
TI  - First isolation of dengue 1 virus from Aedes aegypti in Federal District, Brazil.
AB  - Dengue is present in the Federal District since 1991 and virological studies of
      the vector began in 1998. Two strains of DEN1 were isolated from 9 pools of
      female Aedes aegypti (78 mosq.), collected in April in Gama county, where the
      Breteau index was 5.4, and 32 autochtonous human cases were notified.

PMID- 10881128
TI  - [Malaria treatment with artesunate (retocaps) in children of the Brazilian
      Amazon].
AB  - We evaluated the clinical and therapeutic response to artesunate retocaps in 32
      children admitted to the Fundacao de Medicina Tropical do Amazonas (Amazon
      Foundation of Tropical Medicine) with clinical characteristics of moderate and
      severe malaria. Of these, 29 were infected with P. falciparum and 3 with P.
      vivax. They improved clinically 24 hours after the beginning of therapy, with 33.
      3% of patients without fever, and after 48 hours, 77.2% of the children had no
      fever. The monitoring of asexual forms of the parasites showed that on D2 (day 2
      of treatment) 58.6% of children with P. falciparum infection had no more
      parasites in the blood stream, on D4 all children had negative slides both for P.
      falciparum and for P. vivax infection. In a long-term follow up, we found 66.6%
      recrudescence in P. falciparum patients. The results enabled the conclusion that
      artesunate retocaps are efficient in practice and their use rapidly reduces the
      parasitemia and improves the patients' clinical picture. However, in P.
      falciparum malaria the recrudescence rate was very high. We observed no side
      effects from this drug.

PMID- 10881129
TI  - [Monitoring of lettuce crops of Ribeirao Preto, SP, Brazil].
AB  - The ingesting of raw vegetables plays an important role in the transmission of
      several infectious diseases due to the high frequency of irrigation with
      wastewater. The objective of this study was to evaluate the sanitary conditions
      of all lettuce producing crops in Ribeirao Preto through microbiological and
      parasitological analysis of both irrigation water and lettuce together with the
      implantation of an effective crop monitoring. Laboratory analysis of 129 crops
      showed irregularities in 26 (20.1%) of these: high concentration of fecal
      coliforms in 17% of the lettuce, presence of Salmonella in 3.1% and several
      enteroparasites (Ascaris sp, Ancylostomidae, Strongyloides sp, Hymenolepis nana,
      and Giardia sp ) in 13.1%. Persistent irregularities determined the definitive
      closing down of one producer; all of the remaining 128 crops were eventually
      approved, thus demonstrating the efficacy of lettuce crop monitoring. Crops
      approved in the laboratory analysis were awarded a Sanitary Inspection
      Certificate - an unprecedented procedure in our Country - that resulted in a
      better acceptance of the monitoring.

PMID- 10881131
TI  - [Total mercury in hair samples of inhabitants of Tapajos River, Para State,
      Brazil].
AB  - This study evaluates human exposure to methylmercury in fishermen and their
      families in four villages on the Tapajos river: Rainha, Barreiras, Sao Luis do
      Tapajos and Parana-Mirim. Hair analyses were performed with atomic absorption
      spectophotometry. Total hair mercury levels varied between 2.9mg/g and 71.5mg/g.
      Parana-Mirim showed the lowest level. The highest level was found in Sao Luis do
      Tapajos and Barreiras. The hair mercury was six to seven times higher than the
      established safe limit of 10mg/g. No statistically significant difference was
      found between the mean level of total mercury taken from the inhabitants living
      downstream and upstream in Itaituba village (p > 0.05). These results confirm
      that human exposure to methylmercury is occurring on the Tapajos river and
      suggest that continued fish ingestion in that region is a potential risk factor
      for the appearance of symptoms and signs of Minamata disease. An immediate
      epidemiological survey program is recommended.

PMID- 10881130
TI  - [Iron status, malnutrition and acute phase response in HIV-positive patients].
AB  - Nutritional status and some iron metabolism parameters of acute phase response
      (APR) positive and APR-negative AIDS patients were studied. Twenty-nine AIDS
      patients were submitted to 24h food intake recall, anthropometry, and albumin, C
      reactive protein (CRP), hemoglobin, ferritin, and total iron binding capacity
      (TIBC) measurements. Infection plus serum CRP > 7 mg/dl were criteria for APR
      presence. Protein-energy malnutrition (PEM) was ascertained by body mass index
      (BMI) lower than 18.5 kg/m2 and height-creatinine index (HCI < 70%). PEM (77.8 vs
      40%) and pulmonary tuberculosis (44. 4 vs 9.5%) were more frequent in APR
      positive patients, which also had lower serum albumin (3.7 +/- 0.9 vs 4.3 +/- 0.9
      g/dl), TIBC (165. 8 +/- 110.7 vs 265.9 +/- 74.6 mg/dl) and blood hemoglobin (10.5
      +/- 1. 8 vs 12.6 +/- 2.3g/dl). Iron intake was similar between groups; however,
      serum ferritin levels (median, range) were higher among APR-positive (568, 45.3
      1814 vs 246, 18.4-1577 ng/ml) patients. HIV-positive adults with systemic
      response to invading pathogens showed worse nutritional status than those APR
      negative. In APR-positive AIDS patients, anemia appears to be unrelated to recent
      iron intake.

PMID- 10881132
TI  - [Clinical study of falciparum malaria in children in Manaus, AM, Brazil].
AB  - The clinical characteristics of falciparum malaria were studied among 61
      children, aged 0 to 14 treated at a reference center in Manaus, from October to
      December 1997. The symptoms observed were fever (98.4%), headache (80.3%), chills
      (68.9%), perspiration (65. 6%), myalgia (59.0%), nausea (54.1%), lumbar pain
      (49.2%), vomiting (49.2%), cough (45.9%), arthralgia (31.1%), diarrhea (34.4%),
      dyspnea (8.2%), convulsions (8.2%) and dizziness (4.9%). Pallor and anaemia were
      found more frequently in children under five years old. Anaemia was associated
      with high levels of parasitaemia. Fifty-eight (91.5%) patients had uncomplicated
      malaria, 3 (4.9%) had severe malaria and the lethality was 1.6%.

PMID- 10881133
TI  - [Evaluation of an specific treatment for Trypanosoma cruzi in children, in the
      evolution of the indeterminate phase].
AB  - Twelve chagasic patients between the ages of seven and twelve, in the
      indeterminate phase with serology and xenodiagnosis positive, received the
      specific treatment. Eight of these were evaluated after an eight-year treatment
      period and four were followed-up during 20 years. Two patients took 7 mg/kg of
      nifurtimox during sixty and ninety days and ten of these used 5-7 mg/kg of
      benznidazole during 60 days. The clinical outcome was verified through clinical
      examination, electrocardiogram and contrasted X-ray of the esophagus. After the
      treatment, only one patient presented negativity in all the examinations. Seven
      (58.4%) remained in the indeterminate form and despite the precocious treatment
      four chagasic patients (33.3%) progressed clinically to second degree cardiopathy
      and/or megaesophagus.

PMID- 10881134
TI  - [Reinfections and the development of schistosomal periportal fibrosis in the
      murine model].
AB  - Experimental pipestem fibrosis of the liver developed more frequently (69.2%) in
      mice submitted to repeated infections with Schistosoma mansoni, than with single
      infection (11.1%). The counting of eggs in the liver revealed no significant
      differences between the two experimental groups. Although the reason why multiple
      infections favor the development of pipestem fibrosis has not been elucidated,
      the data obtained represent an experimental support to clinico-epidemiological
      claims that repeated infections play a role in pathogenesis of hepatosplenic
      schistosomiasis

PMID- 10881135
TI  - [RIII mefloquine resistance in children with falciparum malaria in Manaus, AM,
      Brazil].
AB  - We report the occurrence of resistance to mefloquine 20mg/day in 51 children with
      falciparum malaria treated, at reference center of Manaus, Brazil, from October
      to December 1997. All children were evaluated at day 3, 5, 7, 14, 21, 28 and 35
      of treatment. Clinical and parasitological cure criteria were adopted. The
      incidence of RIII mefloquine resistance was 5.9% (IC 95% 1.5-17.2). The
      cure/resistance proportion was 20:1 and cure/severity was 62:1. These findings
      suggest the importance of mefloquine resistance within this group of children.

PMID- 10881136
TI  - [Clinical and laboratory renal alterations in patients with acquired
      immunodeficiency syndrome in relation to anatomopathological findings].
AB  - Clinical as well as renal anatomopathological data of 119 patients with acquired
      immunodeficiency syndrome from the Hospital of the Faculty of Medicine of
      Triangulo Mineiro, Uberaba, MG, Brazil, were studied. Mean age was 33 +/- 10.4
      years (range 18 to 67 years). White (59%) and male (80%) individuals
      predominated. Ninety percent of patients came from Uberaba or neighborhood. There
      were 59 (50%) heterosexual, 25 (21%) homosexual, 17 (14%) bisexual and 18 (15%)
      unknown. Forty three percent were drug abusers. Fourteen (12.2%) of patients had
      serum creatinine higher than 3mg/dl, ten days before death, 64% of them showed
      acute tubular necrosis. Seventy one (61%) patients presented hyponatremia and 8
      (7%) had hypernatremia. Hypokalemia was detected in 28 (24%) and hyperkalemia in
      8 (7%) patients. Twenty four hours urinary protein was detected in 12 patients, 7
      of them presenting more than 1g/24h. Two patients showed segmentar focal
      glomerulosclerosis, one of them with 24h urinary protein level of 5.5 g and serum
      creatinine 1.5 mg/dl and no edema. The most (56%) patients had tubulointerstitial
      nephritis. Clinical, laboratory and types of renal disorders in patients with
      acquired immunodeficiency syndrome are variable. The glomerular diseases were
      relatively scarce however, tubulointerstitial lesions are quite frequent, mainly
      interstitial nephritis and acute tubular necrosis. Not always an anatomoclinical
      correlation could be observed, because many times the electrolyte disorders were
      frequently observed only functionally.

PMID- 10881137
TI  - [Rational for morbidity management in bancroftian filariasis endemic areas].
AB  - Selection of the most appropriate therapy for the patient with bancroftian
      filariasis requires a knowledge of the diverse clinical characteristics of
      filarial disease and their pathogenesis. As a result of new diagnostic tests and
      clinical advances, our understanding of bancroftian filariasis has changed
      rapidly, as have our ideas about treatment. In the past, it was believed that
      elephantiasis was caused by an immunologic reaction of the host to the filarial
      parasite. From this perspective, elephantiasis was seen as the endpoint of an
      unalterable relationship between the host and the parasite, and given the absence
      of effective medication or procedures, affected individuals were considered
      "immunologically predisposed" to this end-stage disease. In the last few years,
      however, new evidence has suggested that lymphedema and elephantiasis have
      another etiologic agent. Namely, the principal factor in the evolution of
      lymphedema and elephantiasis is the involvement of recurrent secondary bacterial
      infections. Today, it is clear that other forms of supportive therapy (including
      education and psychological counseling) are necessary and are often more
      important than antiparasitic drugs.

PMID- 10881138
TI  - The comparison of the Butzler medium, filtration technique and their association
      with isolation of Campylobacter ssp.
AB  - Campylobacter was isolated in 178 out of 622 stool samples (200 porcine, 220
      bovine, and 202 canine). From these 178 samples, the microorganism was identified
      in 64 samples (36%) isolated only in Butzler selective medium (BSM), 34 samples
      (19%) using filtration technique (FT), and in 80 samples (45%) using both BSM and
      FT. Comparison of the proportion of positivity using both techniques showed a
      significant value (chi2 = 9,184; p > 0.001); BSM (36%) being more efficient than
      FT (19%). The use of both techniques yielded the highest isolation positivity
      (45%).

PMID- 10881139
TI  - [Specific treatment attempt, with ticlopidine, of patients with Chagas disease
      chronic phase].
AB  - In a previous study, ticlopidine decreased the parasitemia and mortality of mice
      infected by Trypanosoma cruzi. Therefore, this drug was administered to 12
      patients with Chagas' disease, in the chronic phase. For 90 days, 150, 200 or 250
      mg were utilized according to whether the recipients were children, adolescents
      or adults, respectively. A fully unsuccessful outcome was documented, both
      serologically as well as parasitologically.

PMID- 10881140
TI  - [Note on the types and specimens of triatomine deposited in the Entomological
      Collection of Instituto Butantan, Sao Paulo (Hemiptera:Reduviidae)].
AB  - A list of 8 type specimens belonging to the Subfamily Triatominaeis deposited in
      the Entomological Collection of the Instituto Butantan. This note reports a
      chronological description of the Collection including 343 specimens represented
      by 5 species of Panstrongylus, 18 species of Triatoma, 2 species of Psamolestes
      and Rhodnius.

PMID- 10881141
TI  - [Creative process and epidemiological recognition of Chagas' disease in Mexico].

PMID- 10881142
TI  - [Chagas disease in the context of sports activities: recommendations].

PMID- 10881143
TI  - [The Science and basic human needs].

PMID- 10881144
TI  - [Infections resurgence].

PMID- 10881145
TI  - Breast cancer in Mexican women: an epidemiological study with cervical cancer
      control.
AB  - INTRODUCTION: In Mexico, breast cancer (BC) is one of the main causes of cancer
      deaths in women, with increasing incidence and mortality in recent years.
      Therefore, the aim of the study is identify possible risk factors related to BC.
      METHODS: An epidemiological study of hospital cases of BC and controls with
      cervical uterine cancer (CUCA) was carried out at eight third level concentration
      hospitals in Mexico City. The total of 353 incident cases of BC and 630 controls
      with CUCA were identified among women younger than 75 years who had been
      residents of the metropolitan area of Mexico City for at least one year.
      Diagnosis was confirmed histologically in both groups. Variables were analyzed
      according to biological and statistical plausibility criteria. Univariate,
      bivariate and multivariate analyses were carried out. Cases and controls were
      stratified according to the menopausal hormonal status (pre and post menopause).
      RESULTS: The factors associated with BC were: higher socioeconomic level (OR=
      2.77; 95%CI = 1.77 - 4.35); early menarche (OR= 1.32; 95%CI= 0.88 - 2.00); old
      age at first pregnancy (>31 years: OR= 5.49; 95%CI= 2.16 - 13.98) and a family
      history of BC (OR= 4.76; 95% CI= 2.10 - 10.79). In contrast, an increase in the
      duration of the breastfeeding period was a protective factor (>25 months: OR=
      0.38; 95%CI= 0.20 - 0.70). CONCLUSIONS: This study contributes to the
      identification of risk factors for BC described in the international literature,
      in the population of Mexican women. Breastfeeding appears to play an important
      role in protecting women from BC. Because of changes in women's lifestyles,
      lactation is decreasing in Mexico, and young women tend not to breastfeed or to
      shorten the duration of lactation.

PMID- 10881146
TI  - [Comparison between reference oncologic colpocytology and severity of
      intraepithelial cervical lesions].
AB  - OBJECTIVE: The study was designed to compare the Pap smear results, performed on
      the public health service, with: the results of Pap smear collected on the
      reference service; the colposcopy and punch biopsy results. METHODS: The total of
      213 women assisted at the women's hospital from January 1989 to April 1991, and
      followed until July 1998 were selected. Ninety were referred because a Pap smears
      suggestive of Human Papillomavirus (HPV) induced lesion or cervical
      intraepithelial neoplasia (CIN) grade 1, and 123, CIN 2 or 3. RESULTS: Among the
      90 women referred because of HPV/CIN 1.49% presented CIN 2 or 3 in the Pap smears
      performed at this service. At the colposcopy, 16/90 women did not present
      suspicious lesions, and in 10 women, the squamous columnar junction was not
      observed. At biopsy, 42 (46%) presented CIN 2 or 3. Out of the 123 women referred
      with Pap smear of CIN 2 or 3.54% presented CIN 2 or 3 at this service. At the
      colposcopy, 24 women did not present suspicious lesions and the squamous columnar
      junction was not observed in 12. About biopsy, 61 (49%) presented CIN 2 or 3.
      CONCLUSIONS: The expectant conduct in cases of Pap smear with HPV/CIN 1, should
      follow a criterion, involving qualified professionals to collect the Pap smear,
      and should provide people awareness as to control follow-up.

PMID- 10881147
TI  - The Bambui health and ageing study (BHAS): methodological approach and
      preliminary results of a population-based cohort study of the elderly in Brazil.
AB  - OBJECTIVE: A cohort study has been designed to identify predictors of adverse
      health events in the elderly. The methodology of the study and preliminary
      descriptive results are presented. METHODS: The study population comprises all
      residents of Bambui (Minas Gerais, Brazil), aged 60 or more years (n=1.742). From
      these, 92.2% were interviewed and 85.9% underwent clinical examination,
      consisting of haematological and biochemical tests, serology for Trypanosoma
      cruzi, anthropometric and blood pressure measures and electrocardiogram. Aliquots
      of serum, plasma and DNA were stored for future investigations. The baseline
      interview included sociodemographic characteristics, self-referred health
      condition and history of selected diseases, medication use, health service use,
      source of medical care, physical activities, smoking, drinking and eating habits,
      reproductive history, physical functioning, life events, social support and
      mental health. Individuals are being followed up annually. RESULTS: The following
      characteristics predominated among participants: women (60,0%), married (48.9%)
      or widowed (35.4%), people living in households with up to 2 residents (73.8%),
      heads of family (76.7%), people with monthly income between 1.00 and 2.99
      Brazilian minimum wages (62.0%) and people with up to 4 years of schooling
      (89.1%). The median age was 68 years. Among the cohort members, only 1.7% were
      lost in the first follow-up. CONCLUSIONS: In general, the characteristics of the
      study population were very similar to those from other epidemiological studies of
      the elderly based on large Brazilian cities. The small number of losses to follow
      up indicates that the choice of Bambui was adequate, assuring the feasibility of
      a long term cohort study.

PMID- 10881148
TI  - [Comparison between two cohorts of adolescent mothers in municipality of the
      Southeastern, Brazil].
AB  - OBJECTIVE: To compare the prevalence of pregnancy among adolescents and analyze
      trends in some social and biological variables among two cohorts of adolescent
      mothers in Ribeirao Preto, Brazil, during 1978/79 and 1994. METHODS: Two cohorts
      of adolescent mothers were interviewed shortly after delivery, comprising 943
      women in the first survey (1978/79) and 499 in the second (1994). Both surveys
      covered more than 98% of births in all childbirth clinics. Only singleton
      livebirths from adolescent mothers living in the municipality were included in
      the analysis. The Chi-square test was used for statistical analysis, with a 0.05
      significance level. RESULTS: The percentage of adolescent mothers increased from
      14.1% in 1978/79 to 17.5% in 1994 (p<0.05), mainly due to an increase in
      deliveries in the 13-17 years age group. There was a reduction in the number of
      smokers and mothers with lower schooling. The number of prenatal care visits
      increased. There was also an increase in the proportion of single mothers, of
      those who were employed and got private delivery care. Low birth weight and
      preterm birth rates remained unchanged for all of them. Cesarean section and
      forceps delivery rates increased substantially. Mothers in the 13-17 years age
      group however showed twice as much premature and low birth weight children, a
      higher proportion of single mothers with lower schooling, and higher rate of
      forceps delivery. CONCLUSIONS: Some characteristics of the adolescent mothers in
      the 13-17 years age group were more unfavorable when compared to the 18-19 years
      age group. The characteristics of adolescent age groups need to be better
      understood and taken into account in the prenatal and delivery care planning.

PMID- 10881149
TI  - [Evolution of breastfeeding pattern].
AB  - OBJECTIVE: To follow the evolution of the breastfeeding practice among women in a
      childbirth clinic and evaluate the actions for its promotion. METHODS: Two
      cohorts of children born in an school hospital of Porto Alegre, Brazil, in
      different periods of time were compared regarding the prevalence of breastfeeding
      during the first six months of life, and the percentage of early cessation of
      breastfeeding. Both were prospective studies, including 202 children in the
      cohort of 1987, and 187 children in the cohort of 1994. All participants were
      healthy children, with birth weight of 2500g or more, were being breastfed and
      their parents were living in the same house. The 1987 study children were
      followed up through mail, and the 1994 study ones by home visits. RESULTS:
      Survival analysis showed similar frequencies of breastfeeding in the two cohorts.
      The prevalence of exclusive breastfeeding, although for a short period in both
      groups, was higher in the population studied in 1994, especially among children
      whose mothers were better educated. There was no rate difference of early
      cessation of breastfeeding between the two cohorts (36% for the 1987 cohort and
      39% for the 1994 cohort). CONCLUSIONS: The results revealed a certain degree of
      apathy in regard of the promotion of breastfeeding during the studied period,
      giving support to actions to promote breastfeeding, especially among poor
      families.

PMID- 10881150
TI  - [Characteristics of the victims of traffic accidents in a city of the southern
      region of Brazil].
AB  - OBJECTIVE: To evaluate the magnitude of morbidity and mortality and describe some
      of the characteristics of road accident victims. METHODS: The study population
      was composed of 3,643 victims of road accidents which occurred in Londrina, PR
      (Brazil), during the first semester of 1996. There were included victims from
      accidents registered by the Military Police, those who died at the accident
      scenario or on their way to the hospital, those who received emergency care or
      were hospitalized through the Unified Care System. It was observed a period of
      180 days for death verification. RESULTS: The mean incidence and mortality rates
      were 1,582.2 and 29. 0 per 100,000 inhabitants, respectively. These rates,
      however, have demonstrated great variability in relation to several
      characteristics (place of residence, gender, age and the victim's mode of
      transport). The majority of victims were motorcyclists, followed by cyclists and
      pedestrians who, altogether, accounted for 76.9% of the total, and 81.5% of those
      who died. CONCLUSIONS: These results suggest that road accidents constitute a
      major cause of morbidity and mortality and that specific preventive measures
      should be considered in order to reduce such accidents, especially those that
      involve the most vulnerable road passers.

PMID- 10881151
TI  - [Myocardial infarction hospitalization by the day of the week: retrospective
      study].
AB  - INTRODUCTION: There is in the literature some studies looking for cycles and a
      circadian rhythm associated with acute myocardial infarction. Several authors
      have pointed out a higher incidence of myocardial infarction on Mondays
      suggesting the existence of trigger mechanisms in the disease onset. The week day
      distribution of hospitalizations due to myocardial infarction and its
      associations with patient sex and category of hospitalization (social status) in
      the Ribeirao Preto area from 1987 to 1996, were studied. METHODS: A total of
      173,982 hospitalizations due to heart and cerebral vascular diseases, including
      5,804 cases of acute myocardial infarction, were evaluated using the medical
      records of the Hospital Data Center of the medical school of Ribeirao Preto,
      University of S. Paulo. The hospitalizations were classified as being on a
      private basis, through private insurance or the Unified Health System (SUS). The
      associations with sex, patient condition at discharge and category of the
      hospitalization were studied. RESULTS/CONCLUSIONS: The distribution of
      hospitalizations due to heart and vascular diseases and acute myocardial
      infarction showed a peak incidence on Mondays, corresponding to 19.3% and 16.9%
      of the cases. During the weekend there was a decrease in the number of heart and
      vascular disease hospitalizations (8.6%) and a smaller reduction in the number of
      myocardial infarction cases (12.7%) which are statistically significant. In
      addition, there were observed differences in the distribution patterns according
      to the day of the week and category of hospitalization. While the SUS patients
      (4,120) and private insurance patients (1,225) are more likely to be hospitalized
      on Mondays, private patients (459) are more likely to be hospitalized on Fridays
      and Saturdays. There were no associations with patient sex and patient condition
      at discharge.

PMID- 10881152
TI  - [Microbiological conditions of hospital beds before and after terminal cleaning].
AB  - INTRODUCTION: The hospital's environment keeps a close relationship with hospital
      infection, which may promote focus of contact and transmission. The terminal
      cleaning of patient unit represents one way to control microbiological
      environmental contamination. The study has as its main objective to evaluate the
      microbiological conditions of hospital mattresses before and after cleaning.
      METHODS: Rodac plates were utilized for specimen collection with culture medium -
      blood agar plate. The patients beds were chosen by criteria established before
      hand and the places for specimen collection in the mattress were chosen by
      aleatory drawing. To the study of numerical alteration related to the positivity
      of plates before and after cleaning, Goodman' statistics tests were used.
      RESULTS: From 52 mattress investigated, 520 culture plates were done from which
      514 (98,8%) had a positive culture, 259 before cleaning and 255 after cleaning
      showing a reduction of positive cultures in only 4 plates after cleaning.
      CONCLUSIONS: The number of plates with countable and countless colonies suggests
      that the cleaning, as it is done, instead of reducing the microorganism is
      dislocating it to other areas of the mattress keeping the microbiological
      condition as it was before the cleaning process.

PMID- 10881153
TI  - [Variables associated with underreporting of AIDS patients in Rio de Janeiro,
      Brazil, 1996].
AB  - OBJECTIVE: The underreporting of AIDS cases in the municipality of Rio de
      Janeiro, Brazil, is significant. The study intends to analyze the factors
      associated to this event. METHODS: Using data provided by the Hospital
      Information System for the year of 1996, in Rio de Janeiro city, and by the
      National Surveillance System, patients were randomly selected and their medical
      records reviewed to verify an AIDS diagnosis. A multinomial model was used to
      perform an analysis of the variations on the chances of underreporting of AIDS
      cases versus reporting and on the chances of underreporting without evidences to
      fulfill the case definition of AIDS versus reporting. RESULTS: No significant
      associations were found between the variables such as "age", "marital status",
      "level of education", "occupation", and "severity of illness" and the
      underreporting of AIDS cases. The variable "female gender" showed a strong
      association with hospitalization without evidence of an AIDS diagnosis. A strong
      association was found between two or more admissions in an inpatient unit care
      and reporting. The existence of a epidemiological surveillance department in the
      hospital is inversely associated with the underreporting of AIDS cases.
      CONCLUSION: The significant association between organizational variables and
      underreporting of AIDS cases found in the study point out to the need of
      standardization of the surveillance procedures, the especial need for the
      creation and maintenance of surveillance departments in hospitals to improve the
      quality of the health information system and, therefore, AIDS prevention and
      care.

PMID- 10881154
TI  - [Application of the Portuguese version of the abbreviated instrument of quality
      life WHOQOL-bref].
AB  - INTRODUCTION: The need of short instruments to evaluate Quality of life
      determines World Health Organization Quality of Life Group (WHOQOL Group) to
      develop an abbreviated version of the WHOQOL-100, the WHOQOL-bref. The objective
      is to present the Brazilian field trial of the WHOQOL-bref. METHODS: WHOQOL-bref
      is composed by 26 questions divided in four domains: physical, psychological,
      social relationships and environment. The evaliation instrument, BDI (beck
      depression inventory) and BHS (beck hopelessness scale) were used in a 300
      subjects sample in Porto Alegre, South Brazil. RESULTS/CONCLUSIONS: The
      instrument showed a good performance concerning internal consistency,
      discriminant validity, criterion validity, concurrent validity and test-retest
      reliability. The intrument allies good psychometric performance and practicity
      for use which puts it as an interesting option to evaluate quality of life in
      Brazil.

PMID- 10881155
TI  - [Drug package inserts and the adequacy of patient's drug information].
AB  - OBJECTIVE: To investigate the adequacy of the content and format of the patient
      information section in package inserts of commonly prescribed drugs at the
      internal medicine service of a school hospital. METHODS: Forty eight package
      inserts were collected from six pharmacies of the city of Porto Alegre in June
      1998. The presence of mandatory notification and other information required by
      Brazilian laws that regulate inserts content was examined. RESULTS: No one
      package inserts contained all the notification required by law. Warnings about
      medication storage and expiration date were the most frequently information found
      in package inserts analyzed. CONCLUSION: Important information for the drug user
      was not presented in package inserts analyzed, limiting the purpose of inserts as
      an instrument for patient education.

PMID- 10881156
TI  - [Evaluate of popular knowledge and everyday practices in oral health].
AB  - OBJECTIVE: To evaluate the popular knowledge and everyday practices in oral
      health of public services' users. METHODS: The target population was selected
      from a stratified sample and included users seeking medical care in health care
      units in Santa Maria - RS. The data were collected using a semi-structured
      interview and organized into descriptive categories groups, allowing the
      distribution in a frequency table. RESULTS: It was verified the predominance of
      the age group between 21 to 40 years old and females. The socioeconomic pattern
      is characterized by low schooling and family income. The search for oral diseases
      control are due to individual awareness of the need of oral hygiene and dental
      care; fluoride in toothpaste and drinking water and its benefits were not known
      by the population. CONCLUSIONS: The health programs offered to the population
      must take into account the knowledge and practices in oral health care to make it
      possible an improvement of oral health according to their reality. In addition
      there is a need to promote the collective awareness on health promotion in every
      level of the society.

PMID- 10881157
TI  - [Dental caries prevalence in permanent teeth of schoolchildren in the
      Municipality of Sao Paulo, Brazil, 1970-1996].
AB  - OBJECTIVE: To assess the evolution of dental caries in permanent teeth of
      schoolchildren in S. Paulo City, Brazil, during the period of 1970-1996. METHODS:
      The World Health Organization methodology for oral health surveys was applied in
      2,491 schoolchildren, both male and female from 103 public and private schools. A
      probabilistic sample stratified by age, school category, and city zones was
      obtained by the Education State Service data system. Computational resources were
      used. RESULTS: Data from the 1996 S. Paulo survey were compared with others data
      provided by studies such as the one conducted in the same city and the reference
      population in the second half of the 20th century. In the 60s and 70s the DMF-T
      Index among 12-year-old schoolchildren was around 7.0. In 1986 it was 6.5 and in
      1996 it was registered 2.1, a decline of 68%. CONCLUSION: Dental caries in
      permanent teeth among S. Paulo City 12-year-old schoolchildren changed from a
      "very high" to "low" prevalence.

PMID- 10881158
TI  - [The influence of selection and measurement bias on secular trend in height
      estimates from Brazilian Navy data].
AB  - Data of bias occurrence of secular height trend estimates based on Brazilian Navy
      data are presented. Three data sets were analyzed; one for the 1940-65 period and
      two for the 70s.

PMID- 10881159
TI  - Serological analysis reveals circulation of influenza C viruses, Brazil.
AB  - The circulation of influenza C viruses in Rio de Janeiro, Brazil, was studied
      when significant levels of antibodies were detected (56. 7%) with
      hemagglutination inhibition test, used as a standard methodology for influenza
      virus studies.

PMID- 10881160
TI  - [Drug National Policy].

PMID- 10881161
TI  - Birth of a journal.

PMID- 10881162
TI  - Making smarter immunotherapies.

PMID- 10881163
TI  - The Global Alliance for Vaccines and Immunization--a millennial challenge.

PMID- 10881164
TI  - B cells on the front line.

PMID- 10881165
TI  - Thanks for the memory.

PMID- 10881166
TI  - Preventing injury from within, using selective cPLA2 inhibitors.

PMID- 10881167
TI  - T cell development: some cells get all the breaks.

PMID- 10881169
TI  - Immunology highlights from the recent literature.

PMID- 10881168
TI  - Type 1 IFNs and regulation of TH1 responses: enigmas both resolved and emerge.

PMID- 10881170
TI  - The immunological synapse and the actin cytoskeleton: molecular hardware for T
      cell signaling.
AB  - The actin cytoskeleton seems to play two critical roles in the activation of T
      cells. One of these roles is T cell shape development and movement, including
      formation of the immunological synapse. The other is the formation of a scaffold
      for signaling components. This review focuses on the recent convergence of cell
      biology and immunology studies to explain the role of the actin cytoskeleton in
      creating the molecular basis for immunological synapse formation and T cell
      signaling.

PMID- 10881171
TI  - Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in
      the humoral response.
AB  - The lymphoid organs contain specialized microanatomic structures composed of
      lymphoid, myeloid and stromal cells that are vital to the generation of an
      effective adaptive immune response. Although the existence of these specialized
      structures has been known for over a century, the developmental signals that
      generate them and the specific roles of these structures in the immune response
      have remained largely elusive. Because of their position adjacent to the marginal
      sinuses, marginal zone B (MZB) cells are amongst the first population of cells
      seen by blood born antigens and are presumed to have a critical role in host
      defense against bacterial pathogens. Here we demonstrate that a deficiency of the
      tyrosine kinase (Pyk-2) results in a cell autonomous defect of MZB cell
      production. In response to repetitive polysaccharide antigens (T-independent type
      II (TI-II)) Pyk-2-deficient mice displayed marked suppression of IgM, IgG3 and
      IgG2a production. Furthermore, complement receptor engagement proved necessary
      for the specific targeting of polysaccharide antigens to MZB cells. These results
      suggest how innate immune responses mediated through complement coupling are
      translated into an adaptive response by MZB cells, and provide a potential
      mechanism for the T cell independence of humoral responses to polysaccharide
      antigens.

PMID- 10881172
TI  - Identification of a receptor for BLyS demonstrates a crucial role in humoral
      immunity.
AB  - B lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor (TNF)
      superfamily. BLyS stimulates proliferation of, and immunoglobulin production by,
      B cells. However, the relative importance of BLyS in physiological B cell
      activation is unclear. We identified a B cell receptor for BLyS through
      expression cloning as TACI, an orphan TNF receptor homologue of unknown function.
      Binding of BLyS to TACI activated signaling by nuclear factor-kappa B (NF-kappa
      B). In vitro soluble TACI-Fc fusion protein blocked BLyS-induced NF-kappa B
      activation in B lymphoma cells and IgM production in peripheral blood B cells. In
      vivo treatment of immunized mice with TACI-Fc inhibited production of antigen
      specific IgM and IgGI antibodies and abolished splenic germinal center (GC)
      formation. Thus, BLyS activity must play a critical role in the humoral immune
      response.

PMID- 10881173
TI  - Acute lung injury by sepsis and acid aspiration: a key role for cytosolic
      phospholipase A2.
AB  - Adult respiratory distress syndrome (ARDS) is characterized by acute lung injury
      with a high mortality rate and yet its mechanism is poorly understood. Sepsis
      syndrome and acid aspiration are the most frequent causes of ARDS, leading to
      increased lung permeability, enhanced polymorphonuclear neutrophil (PMN)
      sequestration and respiratory failure. Using a murine model of acute lung injury
      induced by septic syndrome or acid aspiration, we investigated the role of
      cytosolic phospholipase A2 (cPLA2) in ARDS. We found that disruption of the gene
      encoding cPLA2 significantly reduced pulmonary edema, PMN sequestration and
      deterioration of gas exchange caused by lipopolysaccharide and zymosan
      administration. Acute lung injury induced by acid aspiration was similarly
      reduced in mice with a disrupted cpla2 gene. Our observations suggest that cPLA2
      is a mediator of acute lung injury induced by sepsis syndrome or acid aspiration.
      Thus, the inhibition of cPLA2-initiated pathways may provide a therapeutic
      approach to acute lung injury, for which no pharmaceutical agents are currently
      effective.

PMID- 10881174
TI  - Response of naive and memory CD8+ T cells to antigen stimulation in vivo.
AB  - We studied the influence of memory T cell properties on the efficiency of
      secondary immune responses by comparing the in vivo immune response of the same
      numbers of T cell receptor (TCR) transgenic (Tg) naive and memory T cells.
      Compared to naive Tg cells, memory cells divided after a shorter lag time; had an
      increased division rate; a lower loss rate; and showed more rapid and efficient
      differentiation to effector functions. We found that initial naive T cell priming
      resulted in cells expressing mutually exclusive effector functions, whereas
      memory T cells were multifunctional after reactivation, with each individual cell
      expressing two to three different effector functions simultaneously. These
      special properties of memory T cells ensure the immediate control of reinfection.

PMID- 10881175
TI  - Gamma chain required for naive CD4+ T cell survival but not for antigen
      proliferation.
AB  - Lymphoid homeostasis is required to ensure immune responsiveness and to prevent
      immunodeficiency. As such, the immune system must maintain distinct populations
      of naive T cells that are able to respond to new antigens as well as memory T
      cells specific to those antigens it has already encountered. Though both naive
      and memory T cells reside in and traffic through secondary lymphoid organs, there
      is growing evidence that the two populations may be regulated differently. We
      show here that naive T cell survival and memory T cell survival have different
      requirements for cytokines (including the interleukins IL-2, IL-4, IL-7, IL-9 and
      IL-15) that use the common cytokine receptor gamma chain (gamma c). Using
      monoclonal populations of antigen-specific CD4+ T cells, we found that naive T
      cells cannot survive without gamma c, whereas memory T cells show no such
      requirement. In contrast, neither naive nor gamma c-deficient memory T cells were
      impaired in their ability to proliferate and produce cytokines in response to in
      vivo antigenic stimulation. These data call into question the physiological role
      of gamma c-dependent cytokines as T cell growth factors and show that naive and
      memory CD4+ T cell survival is maintained by distinct mechanisms.

PMID- 10881176
TI  - Cloning of a receptor subunit required for signaling by thymic stromal
      lymphopoietin.
AB  - Signaling by type I cytokines involves the formation of receptor homodimers,
      heterodimers or higher order receptor oligomers. Here we report the cloning of a
      type I cytokine receptor subunit that is most closely related to the common
      cytokine receptor gamma chain (gamma c). Binding and crosslinking experiments
      demonstrate that this protein is the receptor for a recently described
      interleukin 7 (IL-7)-like factor, thymic stromal lymphopoietin (TSLP). Binding of
      TSLP to the thymic stromal lymphopoietin receptor (TSLPR) is increased markedly
      in the presence of the IL-7 receptor alpha chain (IL-7R alpha). IL-7R alpha
      expressing but not parental 32D cells proliferate in the presence of exogenous
      TSLP. Moreover, a combination of IL-7R alpha and TSLPR is required for TSLP
      dependent activation of a STAT5-dependent reporter construct. Thus it is shown
      that IL-7R alpha is a component of both the IL-7 and TSLP receptors, which helps
      to explain why deletion of the gene that encodes IL-7R alpha affects the lymphoid
      system more severely than deletion of the gene encoding IL-7 does. Cloning of
      TSLPR should facilitate an understanding of TSLP function and its signaling
      mechanism.

PMID- 10881177
TI  - Selective loss of type I interferon-induced STAT4 activation caused by a
      minisatellite insertion in mouse Stat2.
AB  - The use of murine systems to model pathogen-induced human diseases presumes that
      general immune mechanisms between these species are conserved. One important
      immunoregulatory mechanism involves linkage of innate and adaptive immunity to
      direct the development of T helper subsets, for example toward subset 1 (TH1)
      development through STAT4 activation. In analyzing type I interferon signaling,
      we uncovered a difference between murine and human cells which may affect how
      these two species control linkage between innate and adaptive immunity. We show
      that in humans, type I interferons induce TH1 development and can activate STAT4
      by recruitment to the IFN-alpha receptor complex specifically via the carboxy
      terminus of STAT2. However, the mouse Stat2 gene harbors a minisatellite
      insertion that has altered the carboxy-terminus and selectively disrupted its
      capacity to activate STAT4, but not other STATs. This defect in murine Stat2
      suggests that the signals leading to STAT4 activation and TH1 development in CD4+
      T cells are different between mice and humans.

PMID- 10881178
TI  - Interferon alpha/beta-mediated inhibition and promotion of interferon gamma:
      STAT1 resolves a paradox.
AB  - Induction of high systemic levels of type 1 interferons (IFNs) IFN-alpha and IFN
      beta is a hallmark of many viral infections. In addition to their potent
      antiviral effects, these cytokines mediate a number of immunoregulatory functions
      and can promote IFN-gamma expression in T cells. However, during viral infections
      of mice IFN-gamma production is not always observed at the same time as systemic
      IFN-alpha/beta production and when, elicited at these times, is IFN-alpha/beta
      independent. We demonstrate that type 1 interferons not only fail to induce, but
      also act to inhibit, IFN-gamma expression by both NK and T cells. The mechanism
      of inhibition is dependent upon the IFN-alpha/beta receptor and the signal
      transducer and activator of transcription 1 (STAT1). In the absence of STAT1, not
      only are the IFN-alpha/beta-mediated inhibitory effects completely abrogated, but
      the cytokines themselves can induce IFN-gamma expression. These results indicate
      that endogenous biochemical pathways are in place to negatively regulate NK and T
      cell IFN-gamma expression elicited by IFN-alpha/beta or other stimuli, at times
      of innate responses to viral infections. They also show that type 1 interferon
      signaling can occur through STAT1-dependent and independent mechanisms and
      suggest that efficient induction of IFN-gamma expression by IFN-alpha/beta
      requires STAT1 regulation. Such immunoregulatory pathways may be critical for
      shaping the endogenous innate and virus-specific adaptive immune responses to
      viral infections.

PMID- 10881179
TI  - Brca1 required for T cell lineage development but not TCR loci rearrangement.
AB  - Brca1 (breast cancerl, early onset) deficiency results in early embryonic
      lethality. As Brca1 is highly expressed in the T cell lineage, a T cell-specific
      disruption of Brca1 was generated to assess the role of Brca1 in relation to T
      lymphocyte development. We found that thymocyte development in Brca1-/- mice was
      impaired not as a result of V(D)J T cell receptor (TCR) recombination but because
      thymocytes had increased expression of tumor protein p53. Chromosomal damage
      accumulation and abnormal cell death were observed in mutant cells. We found that
      cell death inhibitor Bcl-2 overexpression, or p53-/- backgrounds, completely
      restored survival and development of Brca1-/- thymocytes; peripheral T cell
      numbers were not totally restored in Brcal-/- p53-/- mice; and that a mutant
      background for p21 (cyclin-dependent kinase inhibitor 1A) did not restore Brca1-/
      thymocyte development, but partially restored peripheral T cell development.
      Thus, the outcome of Brca1 deficiency was dependent on cellular context, with the
      major defects being increased apoptosis in thymocytes, and defective
      proliferation in peripheral T cells.

PMID- 10881181
TI  - Breaking down barriers, building bridges

PMID- 10881180
TI  - CCR5 provides a signal for microbial induced production of IL-12 by CD8 alpha+
      dendritic cells.
AB  - The activation of dendritic cells (DC) to produce interleukin 12 (IL-12) is
      thought to be a key step in the initiation of cell-mediated immunity to
      intracellular pathogens. Here we show that ligation of the C-C chemokine receptor
      (CCR) 5 can provide a major signal for the induction of IL-12 synthesis by the
      CD8 alpha+ subset of DC and that this pathway is important in establishing
      interferon gamma-dependent resistance to the protozoan parasite Toxoplasma
      gondii. These findings support the concept that the early induction of chemokines
      by invading pathogens is a critical step not only for the recruitment of DC but
      also for the determination of their subsequent immunologic function.

PMID- 10881182
TI  - Role of zinc ion in translational accuracy becomes crystal clear.

PMID- 10881183
TI  - Engines of gene expression.

PMID- 10881184
TI  - Variations on ligand-receptor complexes.

PMID- 10881185
TI  - Hierarchical folding of cytochrome c.

PMID- 10881186
TI  - StARTing to understand cholesterol transfer.

PMID- 10881187
TI  - Fixing mistakes.

PMID- 10881188
TI  - Picture story. COX complexes.

PMID- 10881189
TI  - The SsrA-SmpB system for protein tagging, directed degradation and ribosome
      rescue.
AB  - Bacteria contain a remarkable RNA molecule - known alternatively as SsrA RNA,
      tmRNA, or 10Sa RNA - that acts both as a tRNA and as an mRNA to direct the
      modification of proteins whose biosynthesis has stalled or has been interrupted.
      These incomplete proteins are marked for degradation by cotranslational addition
      of peptide tags to their C-termini in a reaction that is mediated by ribosome
      bound SsrA RNA and an associated protein factor, SmpB. This system plays a key
      role in intracellular protein quality control and also provides a mechanism to
      clear jammed or obstructed ribosomes. Here the structural, functional and
      phylogenetic properties of this unique RNA and its associated factors are
      reviewed, and the intracellular proteases that act to degrade the proteins tagged
      by this system are also discussed.

PMID- 10881190
TI  - Structural links to kinesin directionality and movement.
AB  - The kinesin motor proteins generate directional movement along microtubules and
      are involved in many vital processes, including cell division, in eukaryotes. The
      kinesin superfamily is characterized by a conserved motor domain of approximately
      320 residues. Dimeric constructs of N and C class kinesins, with the motor
      domains at opposite ends of the heavy chain, move towards microtubule plus and
      minus ends, respectively. Their crystal structures differ mainly in the region
      linking the motor domain core to the alpha-helical coiled coil dimerization
      domain. Chimeric kinesins show that regions outside of the motor domain core
      determine the direction of movement and mutations in the linker region have a
      strong effect on motility. Recent work on chimeras and mutants is discussed in a
      structural context giving insights to possible molecular mechanisms of kinesin
      directionality and motility.

PMID- 10881191
TI  - Zinc ion mediated amino acid discrimination by threonyl-tRNA synthetase.
AB  - Accurate translation of the genetic code depends on the ability of aminoacyl-tRNA
      synthetases to distinguish between similar amino acids. In order to investigate
      the basis of amino acid recognition and to understand the role played by the zinc
      ion present in the active site of threonyl-tRNA synthetase, we have determined
      the crystal structures of complexes of an active truncated form of the enzyme
      with a threonyl adenylate analog or threonine. The zinc ion is directly involved
      in threonine recognition, forming a pentacoordinate intermediate with both the
      amino group and the side chain hydroxyl. Amino acid activation experiments reveal
      that the enzyme shows no activation of isosteric valine, and activates serine at
      a rate 1,000-fold less than that of cognate threonine. This study demonstrates
      that the zinc ion is neither strictly catalytic nor structural and suggests how
      the zinc ion ensures that only amino acids that possess a hydroxyl group attached
      to the beta-position are activated.

PMID- 10881192
TI  - Structure of Arf6-GDP suggests a basis for guanine nucleotide exchange factors
      specificity.
AB  - Arf6 is an isoform of Arf that localizes at the periphery of the cell where it
      has an essential role in endocytotic pathways. Its function does not overlap with
      that of Arf1, although the two proteins share approximately 70% sequence identity
      and they have switch regions, whose conformation depends on the nature of the
      guanine nucleotide, with almost identical sequences. The crystal structure of
      Arf6-GDP at 2.3 A shows that it has a conformation similar to that of Arf1-GDP,
      which cannot bind membranes with high affinity. Significantly, the switch regions
      of Arf6 deviate by 2-5 A from those of Arf1. These differences are a consequence
      of the shorter N-terminal linker of Arf6 and of discrete sequence changes between
      Arf6 and Arf1. Mutational analysis shows that one of the positions which differs
      between Arf1 and Arf6 affects the configuration of the nucleotide binding site
      and thus the nucleotide binding properties of the Arf variant. Altogether, our
      results provide a structural basis for understanding how Arf1 and Arf6 can be
      distinguished by their guanine nucleotide exchange factors and suggest a model
      for the nucleotide/membrane cycle of Arf6.

PMID- 10881193
TI  - The structure of the transcriptional antiterminator NusB from Escherichia coli.
AB  - We have determined the solution structure of NusB, a transcription
      antitermination protein from Escherichia coli. The structure reveals a novel, all
      alpha-helical protein fold. NusB mutations that cause a loss of function (NusB5)
      or alter specificity for RNA targets (NusB101) are localized to surface residues
      and likely affect RNA-protein or protein-protein interactions. Residues that are
      highly conserved among homologs stabilize the protein core. The solution
      structure of E. coli NusB presented here resembles that of Mycobacterium
      tuberculosis NusB determined by X-ray diffraction, but differs substantially from
      a solution structure of E. coli NusB reported earlier.

PMID- 10881194
TI  - The crystal structure of NusB from Mycobacterium tuberculosis.
AB  - Both prokaryotes and eukaryotes regulate transcription through mechanisms that
      suppress termination signals. An antitermination mechanism was first
      characterized in bacteriophage lambda. Bacteria have analogous machinery that
      regulates ribosomal RNA transcription and employs host factors, called the N
      utilizing (where N stands for the phage lambda N protein) substances (Nus), NusA,
      NusB, NusE and NusG. Here we report the crystal structure of NusB from
      Mycobacterium tuberculosis, the bacterium that causes tuberculosis in humans.
      This molecule shares a similar tertiary structure with the related Escherichia
      coli protein but adopts a different quaternary organization. We show that, unlike
      the E. coli homolog, M. tuberculosis NusB is dimeric both in solution and in the
      crystal. These data help provide a framework for understanding the structural and
      biological function of NusB in the prokaryotic transcriptional antitermination
      complex.

PMID- 10881195
TI  - Observing conformational and activity changes of tet repressor in vivo.
AB  - Effector triggered conformational changes of proteins such as regulators of
      transcription, receptors, or enzymes are the molecular basis for regulation in
      biology. Most proteins perform their biological functions intracellularly, in the
      presence of many potential interaction partners. Studies of conformational
      changes have mainly been performed in vitro using sophisticated physical and
      biochemical methods that usually require purified proteins. Here we describe the
      observation of conformational changes of Tet repressor in the cytoplasm of
      growing Escherichia coli cells, analyzed by ligand dependent disulfide
      crosslinking of cysteine residues substituted into mobile regions of the protein.
      The amount of protein undergoing the structural change is quantitatively linked
      to the concomitant induction of transcription of a reporter gene.

PMID- 10881196
TI  - Conformation of the myosin motor during force generation in skeletal muscle.
AB  - Myosin motors drive muscle contraction, cytokinesis and cell locomotion, and
      members of the myosin superfamily have been implicated in an increasingly diverse
      range of cell functions. Myosin can displace a bound actin filament several
      nanometers in a single interaction. Crystallographic studies suggest that this
      'working stroke' involves bending of the myosin head between its light chain and
      catalytic domains. Here we used X-ray fiber diffraction to test the
      crystallographic model and measure the interdomain bending during force
      generation in an intact single muscle fiber. The observed bending has two
      components: an elastic distortion and an active rotation that generates force.
      The average bend of the force-generating myosin heads in a muscle fiber is
      intermediate between those in crystal structures with different bound
      nucleotides, and the C-terminus of the head is displaced by 7 nm along the actin
      filament axis compared with the in vitro conformation seen in the absence of
      nucleotide.

PMID- 10881197
TI  - Flt3 ligand structure and unexpected commonalities of helical bundles and cystine
      knots.
AB  - Human Flt3 ligand (Flt3L) stimulates early hematopoiesis by activating a type III
      tyrosine kinase receptor on primitive bone marrow stem cells. The crystal
      structure of soluble Flt3L reveals that it is a homodimer of two short chain
      alpha-helical bundles. Comparisons of structure-function relationships of Flt3L
      with the homologous hematopoietic cytokines macrophage colony stimulating factor
      (MCSF) and stem cell factor (SCF) suggest that they have a common receptor
      binding mode that is distinct from the paradigm derived from the complex of
      growth hormone with its receptor. Furthermore, we identify recognition features
      common to all helical and cystine-knot protein ligands that activate type III
      tyrosine kinase receptors, and the closely related type V tyrosine kinase
      receptors.

PMID- 10881198
TI  - Crystal structure of the BMP-2-BRIA ectodomain complex.
AB  - Bone morphogenetic proteins (BMPs) belong to the large transforming growth factor
      beta (TGF-beta) superfamily of multifunctional cytokines. BMP-2 can induce
      ectopic bone and cartilage formation in adult vertebrates and is involved in
      central steps in early embryonal development in animals. Signaling by these
      cytokines requires binding of two types of transmembrane serine/threonine
      receptor kinase chains classified as type I and type II. Here we report the
      crystal structure of human dimeric BMP-2 in complex with two high affinity BMP
      receptor IA extracellular domains (BRIAec). The receptor chains bind to the
      'wrist' epitopes of the BMP-2 dimer and contact both BMP-2 monomers. No contacts
      exist between the receptor domains. The model reveals the structural basis for
      discrimination between type I and type II receptors and the variability of
      receptor-ligand interactions that is seen in BMP-TGF-beta systems.

PMID- 10881199
TI  - Tertiary core rearrangements in a tight binding transfer RNA aptamer.
AB  - Guided by an in vitro selection experiment designed to obtain tight binding
      aptamers of Escherichia coli glutamine specific tRNA (tRNAGln) for glutaminyl
      tRNA synthetase (GlnRS), we have engineered a tRNA mutant in which the five
      nucleotide variable loop sequence 5'-44CAUUC48-3' is replaced by 5'-44AGGU48-3'.
      This mutant tRNA binds to GlnRS with 30-fold improved affinity compared to the
      wild type. The 2.7 A cocrystal structure of the RNA aptamer-GlnRS complex reveals
      major rearrangements in the central tertiary core of the tRNA, while maintaining
      an RNA-protein interface identical to the wild type. The repacked RNA core
      features a novel hydrogen bonding arrangement of the trans Levitt pair G15-U48, a
      new sulfate binding pocket in the major groove, and increased hydrophobic
      stacking interactions among the bases. These data suggest that enhanced protein
      binding to a mutant globular RNA can arise from stabilization of RNA tertiary
      interactions rather than optimization of RNA-protein contacts.

PMID- 10881200
TI  - Discovery and characterization of a family of insecticidal neurotoxins with a
      rare vicinal disulfide bridge.
AB  - We have isolated a family of insect-selective neurotoxins from the venom of the
      Australian funnel-web spider that appear to be good candidates for biopesticide
      engineering. These peptides, which we have named the Janus-faced atracotoxins (J
      ACTXs), each contain 36 or 37 residues, with four disulfide bridges, and they
      show no homology to any sequences in the protein/DNA databases. The three
      dimensional structure of one of these toxins reveals an extremely rare vicinal
      disulfide bridge that we demonstrate to be critical for insecticidal activity. We
      propose that J-ACTX comprises an ancestral protein fold that we refer to as the
      disulfide-directed beta-hairpin.

PMID- 10881201
TI  - Stepwise formation of alpha-helices during cytochrome c folding.
AB  - Two models have been proposed to describe the folding pathways of proteins. The
      framework model assumes the initial formation of the secondary structures whereas
      the hydrophobic collapse model supposes their formation after the collapse of
      backbone structures. To differentiate between these models for real proteins, we
      have developed a novel CD spectrometer that enables us to observe the
      submillisecond time frame of protein folding and have characterized the timing of
      secondary structure formation in the folding process of cytochrome c (cyt c). We
      found that approximately 20% of the native helical content was organized in the
      first phase of folding, which is completed within milliseconds. Furthermore, we
      suggest the presence of a second intermediate, which has alpha-helical content
      resembling that of the molten globule state. Our results indicate that many of
      the alpha-helices are organized after collapse in the folding mechanism of cyt c.

PMID- 10881202
TI  - RNA motifs that determine specificity between a viral replicase and its promoter

PMID- 10881203
TI  - Addiction and its reward process through polymorphisms of the D2 dopamine
      receptor gene: a review.
AB  - Since 1990, association studies have amassed strong evidence implicating the D(2)
      dopamine receptor (DRD2) gene in alcoholism. Specifically, the TaqI A minor (A1)
      allele of the DRD2 gene has been associated with alcoholism. The DRD2 gene has
      also been found to be involved in other substance use disorders including
      cocaine, nicotine and opioid dependence, and obesity. Beyond association studies,
      pharmacologic studies have shown reduced brain D(2) dopamine receptor numbers in
      A1(+) allele carriers (A1A1 and A1A2 genotypes) compared to A1(-) allele carriers
      (A2A2 genotype). Through a number of other approaches, different phenotypes have
      also been identified in subjects with the A1(+) and A1(-) alleles. These include
      metabolic, neurophysiological, neuropsychological, personality, stress and
      treatment studies. It is hypothesized that in an effort to compensate for
      deficiencies in the dopaminergic system, substance abusers may seek to stimulate
      the mesocorticolimbic circuits of the brain, long thought to be important in
      behavioral reward and reinforcement. In effect, one form of the DRD2 gene, the A1
      allele, renders the dopaminergic system inefficient and rewards substance abuse
      that increases brain dopamine levels.

PMID- 10881204
TI  - Reappraisal of the association between the DRD2 gene, alcoholism and addiction.
AB  - We analysed the impact of the TaqI A1 allele of the D2 dopamine receptor gene on
      the risk for alcoholism, trying to depict three explanations frequently proposed
      to explain discrepancies in association and linkage studies: that the A1 allele
      may act as a marker rather than as a vulnerability factor, that stratification
      biases and unevaluated controls may explain positive results, and that the A1
      allele is modifying the phenotype rather than increasing the risk for alcoholism.
      We thus tested another (dinucleotide STRP) marker within the DRD2 gene, selected
      a new homogenous sample of 113 alcoholic patients and 49 unaffected controls
      strictly matched for ethnic origins, and systematically assessed both samples
      with a semi-structured interview to detect (in both samples) alcohol dependence,
      but also such related traits as specificities of complications. The frequency of
      the A1 allele was not significantly different between alcoholics and controls but
      when comparing different subgroups of alcoholics, the A1 allele was significantly
      more frequent in alcoholic patients with somatic complications (OR = 3.00,
      CI[1.37-6.62]), social and professional complications (OR = 2. 72, CI[1.25
      5.90]), or with co-morbid dependence (OR = 2.88, 95% IC [1.16-7.15]). The
      association for co-morbid dependence and somatic complications was also positive
      when taking into consideration both STRP and TaqIA polymorphisms. The A1 allele
      does not increase the risk for alcoholism per se in our sample, but may be
      involved in a related trait which is partially dependent on the diagnosis of
      alcoholism, through a disequilibrium with another close mutation.

PMID- 10881205
TI  - Association of D2 dopamine receptor and alcohol dehydrogenase 2 genes with
      Polynesian alcoholics.
AB  - Alleles of the D2 dopamine receptor (DRD2) and the alcohol dehydrogenase 2 (ADH2)
      genes were determined in 69 French Polynesian alcoholic patients and 57 controls
      matched for racial origin. Three racial groups were studied: pure Polynesians
      (PP), Polynesians mixed with Caucasian (PCA) ancestry and Polynesians mixed with
      Chinese (PCH) ancestry. DRD2 A1 allele frequencies in the alcoholics compared to
      their controls in these groups were: PP,.26 vs.32 (P =. 69); PCA,.44 vs.35 (P
      =.46); PCH,.40 vs 0.39 (P =.88). ADH2 1 allele frequencies in alcoholics compared
      to their controls groups were: PP, .56 vs.62 (P =.66); PCA,.75 vs.56 (P =.09);
      PCH,.78 vs.32 (P =.009). In the PCA group, the combination of the DRD2 A1
      genotypes and the ADH2 1 homozygotes was strongly associated with alcoholism (P
      =. 0027). This preliminary study shows the importance of ascertaining racial
      ancestry in molecular genetic association studies. Moreover, it suggests that a
      combination of genes are involved in susceptibility to the development of
      alcoholism.

PMID- 10881206
TI  - The DRD2 gene and the risk for alcohol dependence in bipolar patients.
AB  - The high co-morbidity between bipolar disorder and alcohol dependence may have
      different explanations, one of them being the existence of common genetic factors
      for the two disorders. Several candidate genes may be involved but the genes
      acting in the dopaminergic pathway may be more specifically involved. We have
      thus tested the role of the gene encoding the D2 dopamine receptor (TaqI A1
      allele) in the potentially shared vulnerability to alcohol dependence and bipolar
      disorder. One hundred and twenty-two French (for at least two generations)
      patients were recruited on the basis of hospital or outpatient files and were
      interviewed with the DIGS. The A1 allele frequencies were compared between four
      groups, namely, with bipolar patients and co-morbid alcohol dependence (N = 21),
      with bipolar patients without alcohol morbidity (N = 31), with alcohol dependence
      without mood disorder (N = 35) and unaffected controls (N = 35). The Hardy
      Weinberg equilibrium for the DRD2 Taq1 A1 genotypes was respected for the sample
      as a whole, and for each subsample. We observed that 42.9% of control subjects
      have at least one A1 allele, a frequency which is not significantly different
      from the one observed in the affected sample as a whole (39.1%), neither from
      patients with alcohol dependence (37.1%), patients with bipolar disorder (48.4%)
      nor patients with alcohol dependence and bipolar disorder (28.6%). The regression
      analysis based on the three variables (bipolar disorder, alcohol dependence and
      interaction between these two disorders) does not explain the presence of the A1
      allele of the DRD2 gene. We thus found no evidence for a significant role of the
      A1 allele of the D2 dopamine receptor gene in the specific association between
      bipolar disorder and alcohol dependence in our sample.

PMID- 10881207
TI  - Genetic vulnerability to drug abuse.
AB  - Addiction to various substances, including drugs and alcohol, probably arises
      from a combination of environmental and genetic factors. The genetic
      vulnerability to drug addiction is supported by several familial, adoption and
      twin studies. However, as in other mental disorders, the genetic vulnerability to
      drug addiction appears complex: these disorders do not follow the rules of
      Mendelian inheritance. Instead, they are probably influenced by multiple
      susceptibility genes, each of which contributes to the disorder. The more genes
      necessary for a disorder, the harder it is to detect any of them. This difficulty
      is magnified by the role of environmental factors. Association studies using the
      candidate gene approach can identify susceptibility genes for drug abuse
      supported by the pathophysiological hypothesis of the illness. This review will
      focus on the clinical and molecular genetic studies in drug abuse.

PMID- 10881208
TI  - Addiction and schizophrenia.
AB  - Epidemiologic studies in the general population and those based on the clinical
      assessment of schizophrenic populations have revealed a high degree of overlap
      between schizophrenia and addictive disorders. The abuse of psychoactive
      substances (including alcohol) throughout life is so frequent (50%) that the
      possibility of a specific link inevitably arises. Various hypotheses have been
      suggested to explain the high co-morbidity between schizophrenia and addiction:
      1) The social-environmental hypothesis has been developed but studies have
      provided poor evidence to validate it. 2) The possible shared biological
      vulnerability between schizophrenia and addictions led researchers to explore
      common genetic determinants and study the involvement of the dopaminergic and
      opioid systems in the aetiology of both schizophrenia and the abuse of and
      dependence on psychoactive drugs. 3) Finally, the theory of self-medication
      suggests that schizophrenics may be attempting to counter the deficit linked to
      their disorders by using the substances they take or their dependency-type
      behaviour to cope with their emotional problems. The clinical profile of
      schizophrenic addicts does seem to display some distinctive features, such as the
      high level of depressive co-morbidity, very high nicotine and alcohol dependence,
      with a very poor prognosis. These patients are difficult to manage; the
      possibility of pharmacologic interactions between the substances they are taking
      and neuroleptic medication calls for prudence, and their compliance is also poor.
      Addictive disorders in schizophrenics are currently a topic of active research
      intended to lead to identifying specific treatments. The early identification of
      addictive disorders in schizophrenics should make it possible to limit their
      development and improve the prognosis.

PMID- 10881209
TI  - Relationships between antisocial personality and alcoholism: genetic hypotheses.
AB  - Genetic factors explain a non-negligible part of the vulnerability to alcohol
      dependence, the genetic influence in males being estimated at around 60%. The
      search for gene(s) potentially implicated in alcoholism is counteracted by the
      clinical heterogeneity of alcoholism, but also by heterogeneity of the etiologic
      factors involved. It is thus necessary to redefine more specific phenotypes with
      more simple determinism, and to focus on more specific subsets of candidate
      genes. In this view, the existence of co-occurrence (presence at the same time,
      whatever the cause) between antisocial personality and alcoholism is frequently
      reported. Three hypotheses have been previously proposed to explain this co
      occurrence. Firstly, it could be a pure artefact or contamination, due to common
      items in diagnostic manuals widely used, such as the DSM or ICD. Secondly,
      antisocial personality and alcoholism could share common etiologic factor(s), and
      determine a 'real' co-morbidity. Finally, common genetic factors between these
      two disorders may exist, with the observation of a co-transmission of both
      disorders more often than expected by chance alone, meaning the existence of co
      aggregation. Each of these three hypotheses will be reviewed and discussed.

PMID- 10881210
TI  - Epidemiology of behavioral dependence: literature review and results of original
      studies.
AB  - The extension of the definition of dependence leads to the consideration of some
      impulsive disorders as a form of dependence disorder. This pathological condition
      is characterized by the repetitive occurrence of impulsive and uncontrolled
      behaviors. Other clinical characteristics are failure to resist an impulse, drive
      or temptation to perform some act harmful to oneself and/or others, an increasing
      sense of tension or excitement before acting out, and a sense of pleasure,
      gratification or release at the time of the behavior or shortly thereafter.
      Behavioral dependences most often described are pathological gambling,
      kleptomania, trichotillomania and compulsive buying. Studies using a specific
      assessment scale, the South Oaks Gambling Screen, distinguished problem gambling
      from pathological gambling. Social gamblers spend 5% of their money and
      pathological gamblers 14 to 45%. Prevalence of 'problem gambling' is 4% and
      pathological gambling 2%. Several studies have suggested that the incidence of
      pathological gambling is eight to ten times greater in alcohol-dependent patients
      than in the general population. No systematic study has assessed the prevalence
      of kleptomania. Data come from case reports. Among subjects arrested after a
      theft, prevalence of kleptomania varied between 0 and 24%. Trichotillomania
      prevalence rate is 0.6% among students. Studies using less restrictive diagnostic
      criteria found a prevalence rate of 3.4% in women and 1.5% in men. The disorder
      is often unrecognized; 40% of the cases are not diagnosed and 58% of the patients
      have never been treated. Prevalence studies of compulsive buying found a rate
      between 1 and 6% in the general population. Compulsive buying is significantly
      more frequent among women (90% of the cases). Study of family history of
      compulsive buyers showed a high frequency of alcohol-dependence disorder (20%)
      and depression (18%). In all cases of behavioral dependence disorders, a high
      level of impulsivity and sensation-seeking could determine an increased risk.

PMID- 10881211
TI  - Genetics of alcohol withdrawal.
AB  - Alcohol withdrawal is a clinically and etiologically heterogeneous syndrome
      caused by a complex interaction of environmental (e.g., amount of ethanol) and
      genetic factors. Multiple genes are considered to be involved in various
      components of the syndrome, each of them contributing only modestly to withdrawal
      vulnerability. Association studies using candidate genes of the dopamine,
      serotonin, gabaergic and opioidergic systems are reviewed and methodological
      limitations are discussed.

PMID- 10881212
TI  - Dopamine D3 receptor agents as potential new medications for drug addiction.
AB  - All drugs abused by humans increase dopamine in the shell of nucleus accumbens,
      which implicate the neurons of this structure in their hedonic and reinforcing
      properties. Among the various dopamine receptor subtypes, the D(1) (D(1)R) and
      D(3) (D(3)R) receptors co-localise in accumbal shell neurons. Synergistic
      D(1)R/D(3)R interactions at this level were found on gene expression and during
      induction and expression of behavioral sensitisation to levodopa in rats bearing
      unilateral lesions of dopamine neurons. Behavioral sensitisation to abused drugs
      is a component of their long-term effects. Converging pharmacologic, human
      postmortem and genetic studies suggest the involvement of the D(3)R in
      reinforcing effects of drugs; D(3)R agonists reduced cocaine self-administration
      in rats, without disrupting the maintenance of self-administration. These data
      suggest the use of D(3)R agonists as partial substitutes to treat cocaine
      dependence, by affecting its reward component. However, substitution therapies
      maintain dependence and may be inefficient on drug craving and relapse, which are
      the unsolved and critical problems in the treatment of drug addiction. Recently,
      a highly selective and partial D(3)R agonist was shown to reduce cocaine
      associated cue-controlled behaviour in rats, without having any primary intrinsic
      effects. As drug-associated cues maintain drug-seeking in animals and elicit
      craving and relapse in humans, such D(3)R agents have potential therapeutic
      applications.

PMID- 10881213
TI  - Rating depressed patients: observer- vs self-assessment.
AB  - An overview of the rating scale literature reveals that the clinician now has
      many validated rating scales to choose from to assess his patient's condition. In
      general terms, it is the observer-rating scales that should be used as the
      principal outcome criterion in depressive disorders, both in general practice and
      in drug-related trials. However, self-rating scales can provide important
      additional information for therapy evaluation. They also provide a measure of the
      patient's perception of his own illness and recovery, which is not possible with
      observer ratings. Self-rating scales are designed for frequent use and to be
      sensitive to the change brought about by therapy and its time course. Observer
      ratings can also show sensitivity for change, and these compare well with the
      self-rating measures. The multimethod approach, including both observer- and self
      rating scales, and covering different domains such as psychopathological
      symptoms, social functioning, etc. , is the preferred method for assessing
      patients. Using this approach, clinicians are able to build up complete profiles
      of their patients' illnesses and make full assessments of the efficacy of
      treatment and their return to normal social functioning.

PMID- 10881214
TI  - Subthreshold depressive and anxiety disorders in the elderly.
AB  - The aims of the present study were to compare the current and lifetime
      prevalences for major and subthreshold affective disorders in elderly subjects in
      the general population, to assess the influence of demographic variables on
      prevalence rates, and to examine co-morbidity between these disorders. Major and
      subthreshold disorders were diagnosed in 286 subjects (aged >/= 60 years). Four
      point-nine percent of the subjects had a lifetime diagnosis of major depression,
      31.8% either minor or recurrent brief depression, 6.6% a major anxiety disorder,
      and 18.5% a subthreshold anxiety disorder. The risk for current and lifetime
      subthreshold anxiety was higher in females than in males, the lifetime prevalence
      for subthreshold anxiety disorders was increased in elderly subjects and subjects
      with low professional levels. Increased co-morbidity between major and
      subthreshold depressive and anxiety disorders could not be observed. In the
      elderly, subthreshold depressive and anxiety disorders are frequent, more so than
      major affective disorders. The presence of subthreshold anxiety disorders, but
      not subthreshold depression, is influenced by age, gender, and previous
      professional level. Further research focusing on detection, evaluation of risk
      factors and the relevance for the quality of life in the elderly general
      population is needed.

PMID- 10881215
TI  - The prevalence of suicidal ideation and suicidal attempts among Norwegian
      physicians. Results from a cross-sectional survey of a nationwide sample.
AB  - Physicians have a higher suicide rate than the general population or other
      academics. Little is known about the reasons for this. Analysing risk factors may
      be a valuable way of identifying reasons for the high suicide rate among
      physicians, thereby leading to preventive efforts. The present study is one of
      the first papers on suicidal thoughts and attempts among physicians. A
      questionnaire about suicidal thoughts (developed by E.S. Paykel) was completed by
      1,063 of 1,476 active Norwegian physicians (72%). Lifetime prevalence ranged from
      51.1% for feelings that life was not worth living to 1.6% for a suicide attempt.
      Risk factors were being female, living alone, and depression. Suicidal thoughts,
      however, were hardly attributed to working conditions. A high rate of suicide and
      a low rate of suicidal attempts support the hypothesis that physicians do not
      'cry for help,' but are inclined to act out their suicidal impulses.

PMID- 10881217
TI  - Level of caregiver burden among relatives of the mentally ill in South Verona.
AB  - Identifying the burden of care on relatives of the mentally ill remains an
      integral part of research in community psychiatric services. The present study
      aimed to assess the level and extent of burden on relatives in South Verona
      (northeast Italy). The South Verona catchment area provides a comprehensive,
      community-based psychiatric service with minimal reliance on the hospital.
      Patients were selected from the South Verona Psychiatric Case Register and 40 of
      their relatives were interviewed using structured assessments measuring objective
      burden, patient behaviour, coping strategies, satisfaction and needs for
      services. Both positive and negative aspects of burden were apparent, 92% of
      relatives continued to maintain contact with friends/relatives, 72% had no change
      to their family income, and 52% could manage any household disruptions during a
      crisis. The main negative effects for relatives included reduced leisure
      activities (57%) and psychological problems (67%). The greatest burden was on
      relatives of patients who were male (P = 0. 016), unemployed (P = 0.013) and
      diagnosed with psychosis (P = 0. 041). The implications of employment for
      patients and its association with lower levels of caregiver burden are discussed.

PMID- 10881216
TI  - Neurochemical variables in subjects with adjustment disorder after suicide
      attempts.
AB  - The investigation of biological correlates of suicidal behavior is important for
      identifying high-risk subjects. The objective of this study was to examine the
      neurochemical variables' platelet MAO activity and urinary MHPG, 5HIAA and HVA,
      the main metabolites of noradrenaline, serotonin and dopamine, neurotransmitters
      that are considered to be involved in the pathophysiology of suicidal behavior,
      as well as plasma cortisol, in a group of subjects with adjustment disorder after
      a suicide attempt. Fifty-three patients, 42 females and 11 males, were included
      in the study and were compared to a group of 50 healthy controls, 25 females and
      25 males. Platelet MAO activity was found to be significantly lower in both male
      and female patients compared to controls of the same sex (P < 0. 001 for both
      comparisons). 5HIAA and HVA were not different between patients and controls, but
      MHPG was significantly higher in the patients group (P = 0.008). Moreover, plasma
      levels of cortisol were significantly higher in the patients compared to the
      controls (P < 0. 001). Our results confirm the hypothesis of low platelet MAO
      activity as a biological characteristic of patients who attempt suicide. They
      also point to a possible parallel activation of the noradrenergic system.

PMID- 10881218
TI  - Sex differences in the contact rates and utilization of psychiatric services. A
      three-year follow-up study in northern Finland.
AB  - Sex differences in the use of psychiatric services were studied in the Oulu
      University Central Hospital in Finland during a three-year follow-up. A one-year
      treated incidence cohort of new patients was used. The total cohort comprised 537
      patients (46.7% were males). The annual incidence rate was 6.7 per 1,000 members
      of the adult population for both males and females. Compared to females, males
      were younger, more often unemployed, unmarried and lived alone or with parents,
      and did not as often have an apartment of their own. Males predominated among
      organic psychoses, personality disorders and dependencies, females among neurotic
      disorders. Males more often had had previous inpatient care and inpatient care at
      index contact, and had more admissions, compulsory admissions and emergency
      outpatient contacts than females. However, there were no sex differences in the
      use of planned outpatient contacts, in the duration of hospital care and in the
      total consumption of psychiatric care. Male gender was an independent predictor
      of hospital admissions.

PMID- 10881219
TI  - Coercion and restrictions in psychiatric inpatient treatment.
AB  - To find out to what extent coercion and restrictions are used in psychiatric
      inpatient treatment and with which patient characteristics the use of coercion is
      associated. To this end, the hospital records of 1,543 admissions (six-month
      admission samples) to the psychiatric clinics in three Finnish university towns
      were evaluated by retrospective chart review. The study clinics provide all
      psychiatric inpatient treatment for the working-age population in their catchment
      areas. Use of coercion and restrictions was recorded in a structured form.
      Coercion and restrictions were applied to 32% of the patients. Mechanical
      restraints were used on 10% of the patients, and forced medication on 8%.
      Compared to international statistics the figures in the current study are high.

PMID- 10881220
TI  - Atypical antipsychotics in ordinary clinical practice: a pharmaco-epidemiologic
      survey in a south London service.
AB  - The introduction of atypical antipsychotics has triggered a reevaluation of
      treatment strategies in schizophrenia. Although research findings inform about
      the efficacy and safety of drugs, it is the decisions made daily in ordinary
      practice that affect the vast majority of patients. The aim of this paper was to
      examine the use of atypical antipsychotics in clinical care, by means of a survey
      of prescribing practices for clozapine, risperidone, olanzapine, sertindole and
      quetiapine for all patients treated for DSM-IV schizophrenia within a psychiatric
      service. Seventy-five (26%) of the 286 patients identified were on atypical
      antipsychotics. Patients on clozapine were mostly male, had more than 15 years of
      contact with psychiatric services and were poor responders. Patients prescribed
      other atypicals had responded to prior treatment with typical neuroleptics and
      had less than five years of contact with psychiatric services. Gender
      distribution was equal in this group. The use of research criteria for treatment
      resistance identified only one patient, as prolonged use of high-dose
      neuroleptics was uncommon. The new atypical antipsychotics appear to be replacing
      older neuroleptics as the first-line treatment of schizophrenia while clozapine
      is mostly reserved for poor responders. Clinicians' definition of treatment
      resistance was variable and below the threshold used in research.

PMID- 10881238
TI  - Sex chromosomes, testosterone, and the brain.

PMID- 10881239
TI  - Practice makes perfect: sharper tactile perception in the blind.

PMID- 10881240
TI  - Practice parameter: risk of driving and Alzheimer's disease (an evidence-based
      review): report of the quality standards subcommittee of the American Academy of
      Neurology.
AB  - Studies of automobile accident frequency among drivers with AD have yielded
      conflicting results about the risk of accidents. To develop a practice parameter
      regarding driving and AD the authors performed a systematic review of the
      literature. The authors identified well-designed, controlled studies of driving
      and AD using the National Library of Medicine's MEDLINE database. The authors
      also compared the relative rates of crashes and other performance measurements of
      driving ability in the populations studied. Driving was found to be mildly
      impaired in those drivers with probable AD at a severity of Clinical Dementia
      Rating (CDR) 0.5. This impairment was no greater than that tolerated in other
      segments of the driving population (e.g., drivers age 16 to 21 and those driving
      under the influence of alcohol at a blood alcohol concentration [BAC] < 0.08%).
      Drivers with AD at a severity of CDR 1 were found to pose a significant traffic
      safety problem both from crashes and from driving performance measurements.

PMID- 10881241
TI  - Ovariectomy and 17beta-estradiol modulate the levels of Alzheimer's amyloid beta
      peptides in brain.
AB  - OBJECTIVE: To test whether female gonadal hormone status and estrogen modulate
      the metabolism of Abeta peptides in vivo. BACKGROUND: AD is a neurodegenerative
      disorder characterized by accumulation of aggregated forms of the 40- and 42
      amino acid Abeta peptides (Abeta40 and Abeta42). Estrogen replacement therapy in
      postmenopausal women is associated with decreased risk for AD or delay in disease
      onset or both. The mechanism by which estrogen exerts this neuroprotective effect
      is elusive. 17beta-estradiol (E2) was shown to reduce the release of Abeta
      peptides by primary neuronal cultures of murine and human origin. METHODS: For
      this purpose, four experimental sets of guinea pigs were used: intact animals,
      ovariectomized animals (ovx), and ovariectomized animals that received E2 at two
      different doses (ovx+low-dose E2 and ovx+high-dose E2). Brain Abeta40 and Abeta42
      levels were assessed using Abeta40 and Abeta42-specific ELISA assays. RESULTS:
      Prolonged ovariectomy resulted in uterine atrophy and decreased serum E2 levels
      and was associated with a pronounced increase in brain Abeta levels. Total brain
      Abeta in the ovx animals was increased by 1. 5-fold on average as compared to
      intact controls. E2 treatment of ovariectomized animals led to uterine
      hypertrophy and a dose-dependent increase in serum E2 levels. In addition, both
      doses of E2 significantly reversed the ovariectomy-induced increase in brain
      Abeta levels. The high-dose E2 treatment did not lead to a further decrease in
      brain Abeta beyond that observed with the low-dose E2 treatment. CONCLUSIONS: Our
      results infer that cessation of ovarian estrogen production in postmenopausal
      women might facilitate Abeta deposition by increasing the local concentrations of
      Abeta40 and Abeta42 peptides in brain. In addition, our finding that E2 treatment
      is associated with diminution of brain Abeta levels suggests that modulation of
      Abeta metabolism may be one of the ways by which estrogen replacement therapy
      prevents or delays the onset of AD or both in postmenopausal women.

PMID- 10881242
TI  - NeuroImages. "Owl's eyes" of CMV ventriculitis.

PMID- 10881243
TI  - Brain morphology in Klinefelter syndrome: extra X chromosome and testosterone
      supplementation.
AB  - OBJECTIVE: This study focuses on variation in brain morphology associated with
      supernumerary X chromosome and Klinefelter syndrome (KS). Using an unselected
      birth cohort of KS subjects and high-resolution MRI, the authors investigated the
      neuroanatomic consequences of the 47,XXY karyotype in the presence and absence of
      exogenous testosterone supplementation. METHODS: Regional brain volumes were
      measured in 10 subjects with KS and 10 age-matched control men. Five of the KS
      subjects had received testosterone supplementation since puberty (KS+T) and five
      had not (KS-T). RESULTS: KS subjects showed significant (p < 0.01) reduction in
      left temporal lobe gray matter volumes compared with normal control subjects.
      Differences in left temporal gray volumes were also significant between the KS+T
      and KS-T groups (p < 0.01). Verbal fluency scores were significantly different
      between the KS+T and KS-T groups as well. CONCLUSION: Supernumerary X chromosome
      material in men is associated with a reduction in left temporal lobe gray matter,
      a finding that is consistent with the verbal and language deficits associated
      with KS. Also, relative preservation of gray matter in the left temporal region
      is associated with exposure to exogenous androgen during development. A history
      of testosterone supplementation also appears to be associated with increased
      verbal fluency scores in KS patients.

PMID- 10881244
TI  - Subcortical volumes in girls with tourette syndrome: support for a gender effect.
AB  - OBJECTIVE: To test whether girls with Tourette syndrome (TS) show subcortical
      morphology that differentiates them from control subjects. METHODS: MRI-based
      subcortical assessment was completed on 19 girls with TS age 7 to 15 years, 11
      with TS only, and 8 with TS plus attention deficit hyperactivity disorder (TS +
      ADHD), and on 21 age- and sex-matched controls. The structures measured were the
      caudate, putamen, globus pallidus, and lateral ventricle volumes. Whole-brain
      corrected volumes and asymmetry indices were compared using two- and three-group
      designs (i.e., TS versus control; TS-only versus TS + ADHD versus control).
      RESULTS: Two-group comparisons demonstrated no robust significant differences
      between girls with TS and gender-matched controls. Three-group comparisons
      demonstrated that TS-only subjects had significantly small lateral ventricles
      compared with TS + ADHD and control subjects. Because the two-group comparisons
      of the current study differed from previous reports of putamen asymmetry index as
      a marker for TS, retrospective comparisons with data from boys were performed.
      These additional comparisons showed that girls with TS had putamen asymmetry
      indices similar to those of boys with TS; however, control girls also showed
      those same patterns. CONCLUSIONS: Basal ganglia volume and asymmetry differences
      do not distinguish the girls with TS from matched controls. Gender differences
      confound the association between putamen asymmetry and TS. Although the numbers
      are small and the clinical significance is unclear, this study further indicates
      that girls with TS-only have smaller lateral ventricular volumes than control
      subjects and those with TS + ADHD.

PMID- 10881245
TI  - Tactile spatial resolution in blind braille readers.
AB  - OBJECTIVE: To determine if blind people have heightened tactile spatial acuity.
      BACKGROUND: Recently, studies using magnetic source imaging and somatosensory
      evoked potentials have shown that the cortical representation of the reading
      fingers of blind Braille readers is expanded compared to that of fingers of
      sighted subjects. Furthermore, the visual cortex is activated during certain
      tactile tasks in blind subjects but not sighted subjects. The authors
      hypothesized that the expanded cortical representation of fingers used in Braille
      reading may reflect an enhanced fidelity in the neural transmission of spatial
      details of a stimulus. If so, the quantitative limit of spatial acuity would be
      superior in blind people. METHODS: The authors employed a grating orientation
      discrimination task in which threshold performance is accounted for by the
      spatial resolution limits of the neural image evoked by a stimulus. The authors
      quantified the psychophysical limits of spatial acuity at the middle and index
      fingers of 15 blind Braille readers and 15 sighted control subjects. RESULTS: The
      mean grating orientation threshold was significantly (p = 0.03) lower in the
      blind group (1.04 mm) compared to the sighted group (1.46 mm). The self-reported
      dominant reading finger in blind subjects had a mean grating orientation
      threshold of 0.80 mm, which was significantly better than other fingers tested.
      Thresholds at non-Braille reading fingers in blind subjects averaged 1.12 mm,
      which were also superior to sighted subjects' performances. CONCLUSION: Superior
      tactile spatial acuity in blind Braille readers may represent an adaptive,
      behavioral correlate of cortical plasticity.

PMID- 10881246
TI  - Adjunctive therapy with oxcarbazepine in children with partial seizures. The
      Oxcarbazepine Pediatric Study Group.
AB  - OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) as
      adjunctive therapy in children with inadequately controlled partial seizures on
      one or two concomitant antiepileptic drugs (AEDs). BACKGROUND: OXC has shown
      antiepileptic activity in several comparative monotherapy trials in newly
      diagnosed patients with epilepsy, and in a placebo-controlled monotherapy trial
      in hospitalized patients evaluated for epilepsy surgery. DESIGN: A total of 267
      patients were evaluated in a multicenter, randomized, placebo-controlled trial
      consisting of three phases: 1) a 56-day baseline phase (patients maintained on
      their current AEDs); 2) a 112-day double-blind treatment phase (patients received
      either OXC 30-46 mg/kg/day orally or placebo); and 3) an open-label extension
      phase. Data are reported only from the double-blind treatment phase; the open
      label extension phase is ongoing. METHODS: Children (3 to 17 years old) with
      inadequately controlled partial seizures (simple, complex, and partial seizures
      evolving to secondarily generalized seizures) were enrolled. RESULTS: Patients
      treated with OXC experienced a significantly greater median percent reduction
      from baseline in partial seizure frequency than patients treated with placebo (p
      = 0.0001; 35% versus 9%, respectively). Forty-one percent of patients treated
      with OXC experienced a > or =50% reduction from baseline in partial seizure
      frequency per 28 days compared with 22% of patients treated with placebo (p =
      0.0005). Ninety-one percent of the group treated with OXC and 82% of the group
      treated with placebo reported > or =1 adverse event; vomiting, somnolence,
      dizziness, and nausea occurred more frequently (twofold or greater) in the group
      treated with OXC. CONCLUSION: OXC adjunctive therapy administered in a dose range
      of 6 to 51 mg/kg/day (median 31.4 mg/kg/day) is safe, effective, and well
      tolerated in children with partial seizures.

PMID- 10881248
TI  - Access www.neurology.org now for full-text articles

PMID- 10881247
TI  - Oxcarbazepine monotherapy for partial-onset seizures: a multicenter, double
      blind, clinical trial.
AB  - OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) 2,400
      mg/day versus OXC 300 mg/day monotherapy in patients with medically refractory
      partial epilepsy. BACKGROUND: OXC is primarily metabolized by reductase enzymes
      and, consequently, has a low propensity to inhibit or induce oxidative enzymes
      and a minimal potential for drug-drug interactions. The efficacy of OXC as
      monotherapy was shown in several comparative trials in patients with newly
      diagnosed epilepsy and in hospitalized patients undergoing evaluation for
      epilepsy surgery. METHODS: A multicenter, double-blind, randomized, parallel
      group trial design was chosen to assess the antiepileptic efficacy of OXC as
      monotherapy in a refractory epilepsy patient population. Outpatients aged 12
      years or older with inadequately controlled partial seizures, with or without
      secondarily generalized seizures, were enrolled. Patients finished the trial by
      completing the double-blind phase or by meeting one of four predefined exit
      criteria: a twofold increase in partial seizure frequency in any 28-day period
      relative to baseline; a twofold increase in the highest consecutive 2-day partial
      seizure frequency relative to baseline; occurrence of a single generalized
      seizure if none occurred during the 6 months prior to randomization; or
      prolongation or worsening of generalized seizure duration or frequency requiring
      intervention. Adverse events (AEs), vital signs, and clinical laboratory tests
      were evaluated. RESULTS: The percentage of patients meeting one of the exit
      criteria was significantly lower (p < 0.0001) for the OXC 2400 mg/day group
      (14/34; 41%) than the OXC 300 mg/day group (42/45; 93%). In addition, there was a
      significant difference in time to exit in favor of the OXC 2400 mg/day group (p =
      0.0001). In the intent-to-treat analysis, 12% of patients in the OXC 2400 mg/day
      group were seizure-free compared with none in the 300 mg/day group. OXC was well
      tolerated, with dizziness, fatigue, somnolence, and nausea being the most
      frequent AEs. Most of these AEs were transient and rated as mild to moderate in
      intensity. CONCLUSION: OXC is safe and effective in the treatment of patients
      with partial epilepsy previously receiving treatment with other antiepileptic
      drugs. The results of this trial are consistent with previous monotherapy trials
      with OXC.

PMID- 10881249
TI  - [11 C]Flumazenil binding in the medial temporal lobe in patients with temporal
      lobe epilepsy: correlation with hippocampal MR volumetry, T2 relaxometry, and
      neuropathology.
AB  - OBJECTIVE: To detect reduced [11C]flumazenil in patients with temporal lobe
      epilepsy (TLE) and to relate binding to histopathology. METHODS: The authors
      studied 16 patients who underwent epilepsy surgery because of drug-resistant TLE
      using [11C]flumazenil PET and quantitative MRI. In 12 patients, resected
      hippocampus was available for histologic analysis. [11C]Flumazenil binding
      potential (fitted BP) was assessed with the simplified reference tissue model.
      RESULTS: [11C]Flumazenil fitted BP in the medial temporal lobe was reduced in all
      patients with abnormal hippocampal volumetry or T2 relaxometry on MRI. Fitted BP
      was also reduced in 46% of the patients with hippocampal volume within the normal
      range and in 38% of patients with less than 2 SD T2 prolongation. In all MRI
      negative/PET-positive patients, the histologic analysis verified hippocampal
      damage. Also, [11C]flumazenil fitted BP correlated with the severity of reduced
      hippocampal volume, T2 prolongation, and histologically assessed neuronal loss
      and astrogliosis. CONCLUSION: [11C]Flumazenil PET provides a useful tool for
      investigating the hippocampal damage in vivo even in patients with no remarkable
      hippocampal abnormalities on quantitative MRI.

PMID- 10881250
TI  - Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month
      extension. The Galantamine USA-1 Study Group.
AB  - BACKGROUND: Galantamine is a reversible, competitive cholinesterase inhibitor
      that also allosterically modulates nicotinic acetylcholine receptors. These
      mechanisms of action provided the rationale for a therapeutic trial of
      galantamine in AD. METHODS: A 6-month, multicenter, double-blind trial was
      undertaken in 636 patients with mild to moderate AD. Patients were randomly
      assigned to placebo or galantamine and escalated to maintenance doses of 24 or 32
      mg/d. Eligible patients then entered a 6-month, open-label study of the 24 mg/d
      dose. Primary efficacy measures were the 11-item AD Assessment Scale cognitive
      subscale (ADAS-cog/11) and the Clinician's Interview-Based Impression of Change
      plus Caregiver Input (CIBIC-plus). The Disability Assessment for Dementia (DAD)
      scale was a secondary efficacy variable. RESULTS: Galantamine significantly
      improved cognitive function relative to placebo; the treatment effects were 3.9
      points (lower dose) and 3.8 points (higher dose) on the ADAS-cog/11 scale at
      month 6 (p < 0.001 in both cases). Both doses of galantamine produced a better
      outcome on CIBIC-plus than placebo (p < 0.05). Therapeutic response to
      galantamine was not affected by APOE genotype. At 12 months, mean ADAS-cog/11 and
      DAD scores had not significantly changed from baseline for patients who received
      galantamine 24 mg/d throughout the 12 months. The most common adverse events,
      which were predominantly gastrointestinal, decreased in frequency during long
      term treatment. There was no evidence of hepatotoxicity. CONCLUSIONS: Galantamine
      is effective and safe in AD. At 6 months, galantamine significantly improved
      cognition and global function. Moreover, cognitive and daily function were
      maintained for 12 months with the 24 mg/d dose.

PMID- 10881251
TI  - A 5-month, randomized, placebo-controlled trial of galantamine in AD. The
      Galantamine USA-10 Study Group.
AB  - OBJECTIVE: To investigate the efficacy and tolerability of galantamine, using a
      slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to
      moderate AD. METHODS: A 5-month multicenter, placebo-controlled, double-blind
      trial. Following a 4-week placebo run-in, patients were randomized to one of four
      treatment arms: placebo or galantamine escalated to final maintenance doses of 8,
      16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD
      Assessment Scale (ADAS-cog), the Clinician's Interview-Based Impression of Change
      plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily
      Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations
      and adverse event monitoring were carried out. RESULTS: After 5 months, the
      galantamine-placebo differences on ADAS-cog were 3.3 points for the 16 mg/day
      group and 3.6 points for the 24 mg/day group (p < 0.001 versus placebo, both
      doses). Compared with placebo, the galantamine 16- and 24-mg/day groups also had
      a significantly better outcome on CIBIC-plus, activities of daily living, and
      behavioral symptoms. Treatment discontinuations due to adverse events were low in
      all galantamine groups (6 to 10%) and comparable with the discontinuation rate in
      the placebo group (7%). The incidence of adverse events in the galantamine
      groups, notably gastrointestinal symptoms, was low and most adverse events were
      mild. CONCLUSIONS: Galantamine 16 and 24 mg/day significantly benefits the
      cognitive, functional, and behavioral symptoms of AD as compared with placebo.
      Slow dose escalation appears to enhance the tolerability of galantamine,
      minimizing the incidence and severity of adverse events.

PMID- 10881253
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PMID- 10881252
TI  - Differentiating frontal and temporal variant frontotemporal dementia from
      Alzheimer's disease.
AB  - OBJECTIVE/BACKGROUND: To determine whether difficulty in the early
      differentiation between frontotemporal dementia (FTD) and AD may arise from a
      failure to discriminate between the temporal and frontal variants of FTD.
      METHODS: Neuropsychological profiles of patients with early dementia of Alzheimer
      type (DAT; n = 10), the temporal variant of FTD (tv-FTD or semantic dementia; n =
      5), and the frontal variant of FTD (fv-FTD; n = 10) were compared to each other
      and normal controls (n = 10). Structural MRI demonstrated temporal lobe atrophy
      in the tv-FTD patients and frontal lobe atrophy in the fv-FTD group. RESULTS:
      Subjects with tv-FTD showed severe deficits in semantic memory with preservation
      of attention and executive function. Subjects with fv-FTD showed the reverse
      pattern. Attention and executive function impairment separated the fv-FTD
      patients from the early DAT subjects, who were densely amnesic. CONCLUSION: The
      double dissociation in performance on semantic memory and attention/executive
      function clearly separated the temporal and frontal variants of FTD and aids the
      early differentiation of FTD from AD. The characteristic cognitive profiles
      reflect the distribution of pathology within each syndrome and support the
      putative role of the inferolateral temporal neocortex in semantic memory, the
      medial temporal lobe structures of the hippocampal complex in episodic memory,
      and the frontal lobes in executive function.

PMID- 10881254
TI  - Differential effects of cocaine and cocaine alcohol on neurocognitive
      performance.
AB  - OBJECTIVE: To investigate the dose-related effects of cocaine with or without
      alcohol use on the CNS by measuring performance on neurobehavioral tests.
      BACKGROUND: Chronic use of cocaine is associated with persistent decrements in
      cognitive function that are most pronounced in heavy users. Specific
      neurobehavioral deficits in areas such as executive function and impulsivity
      would make it difficult for the cocaine abuser to discontinue using drugs.
      Because alcohol is often used in conjunction with cocaine, the CNS effects of
      alcohol when taken with cocaine deserve further investigation. METHOD: The
      authors evaluated the dose-related effects of cocaine and alcohol use on
      performance in a variety of neuropsychological tests after 1 to 3 days of
      abstinence and again after 4 weeks of abstinence. Fifty-six chronic cocaine
      abusers who had used cocaine during the past 24 to 48 hours volunteered to
      perform a battery of neuropsychological tests on two separate occasions during a
      period of enforced abstinence. In addition to using cocaine, most of the
      volunteers consumed alcohol. Approximately half of the participants consumed more
      than 10 alcohol-containing drinks per week. RESULTS: After controlling for the
      effects of age, sex, and intelligence on performance, the authors found dose
      related associations between neurobehavioral performance and cocaine dose and
      alcohol dose. When the influences of cocaine and alcohol on neurobehavioral
      performance were taken separately, cocaine and alcohol each selectively affected
      performance on different neurobehavioral tests after 1 to 3 days of abstinence,
      with these effects persisting after 4 weeks of abstinence. CONCLUSION: The
      concomitant use of cocaine and alcohol may have additive negative effects on the
      brain as compared to the use of only one of these two substances.

PMID- 10881255
TI  - Estrogen improves motor disability in parkinsonian postmenopausal women with
      motor fluctuations.
AB  - OBJECTIVE: To test the efficacy, tolerance, and safety of low-dose oral estrogen
      in postmenopausal women with PD associated with motor fluctuations. BACKGROUND:
      Motor fluctuations in PD may be predictable or unpredictable, and eventually
      affect most patients after long-term levodopa therapy. Although estrogen can
      modulate nigrostriatal dopamine levels, its effects on PD are unclear. METHODS:
      Patients were randomized to receive conjugated estrogen (oral Premarin 0.625 mg
      daily; n = 20) or placebo (n = 20) in a double-blind, parallel-group, prospective
      study over 8 weeks. Existing antiparkinsonian drug regimes were kept unchanged.
      Changes in "on" and "off" periods using patient diaries, Unified Parkinson's
      Disease Rating Scale (UPDRS) score, timed tapping score, and Hamilton Depression
      Scale score were determined by one rater. Subgroup analyses were also performed
      on patients with only predictable motor fluctuations. RESULTS: Both treatment
      groups were similar in age, duration of disease and menopause, antiparkinsonian
      medication, and compliance with test medication and diary assessments. "On" and
      "off" times, and motor score (UPDRS subscale III) improved with estrogen, using
      the Mann-Whitney U test (p < 0.05 after Bonferroni adjustment). Mean "on" time
      improved by 7% (9 hours/week of awake time) in estrogen-treated patients versus a
      deterioration of 0.5% (1.4 hours) in placebo-treated patients (95% confidence
      interval, [CI] of mean difference, 5.73 to 14.9). Mean "off" time improved by 4%
      (4.4 hours/week of awake time) in estrogen-treated patients versus no change in
      placebo-treated patients (95% CI, 1.54 to 7.16). Mean subscale III score improved
      by 3.5 points in estrogen-treated patients versus 0.4 in placebo-treated patients
      (95% CI, 1.02 to 5.18). No other significant changes were observed (p > 0.05).
      Subgroup analyses in patients with only predictable motor fluctuations showed
      similar results, except improvement in mean subscale III score was marginally not
      significant (p = 0.07; 95% CI, 1.06 to 6.24). Five patients on estrogen had
      facial flushing, three had lower abdominal discomfort, and two had mild
      withdrawal vaginal bleeding. The adverse events were mild and resolved without
      sequelae. CONCLUSION: Low-dose estrogen is a safe and effective adjunct therapy
      to existing antiparkinsonian treatment in reducing motor disability in
      postmenopausal women with PD associated with motor fluctuations.

PMID- 10881256
TI  - Aspirin-associated intracerebral hemorrhage: clinical and radiologic features.
AB  - OBJECTIVE: To identify the clinical and radiologic features of intracerebral
      hemorrhage (ICH) in aspirin users. BACKGROUND: Although the benefits of aspirin
      outweigh its hemorrhagic risks for patients at high risk of vascular diseases,
      prolonged use of aspirin is associated with an increased risk of ICH. METHODS:
      The authors enrolled consecutive patients with acute stroke who were admitted to
      a regional hospital from 1993 to 1998 into a stroke registry. From this registry,
      they identified all stroke patients who had ICH confirmed by CT scan and then
      selected those taking regular aspirin before ICH as the study group. For each
      study patient, they selected the immediate next two patients with ICH but not
      taking aspirin as controls. RESULTS: The authors identified 58 aspirin users and
      1193 nonusers among all patients hospitalized for ICH. From the group of
      nonusers, they selected 116 patients as controls. The locations of the hematoma
      were different (p = 0.002), with more lobar hematoma in the aspirin group (32.8%)
      than in the control group (10.3%). Prior cerebrovascular disease was the reason
      for taking aspirin in 37 (64%) patients but five patients had prior ICH.
      CONCLUSIONS: The propensity for lobar hematoma in aspirin-associated ICH suggests
      its pathology may be somewhat different from spontaneous ICH among nonaspirin
      users. Further research to examine the risks and benefits of aspirin use in
      certain subgroups at risk of both thrombotic and hemorrhagic events is needed.

PMID- 10881257
TI  - Sleep disordered breathing in patients with cluster headache.
AB  - OBJECTIVE: To study subjects with active or inactive cluster headache (CH) for
      occult sleep disordered breathing (SDB). BACKGROUND: CH frequently occurs during
      sleep. The authors previously found that symptoms of SDB predicted reported
      occurrence of CH in the first half of the night, which suggested that CH could be
      triggered in some cases by unrecognized SDB. METHODS: The authors performed
      polysomnography in 25 adults (22 men) with CH. Subjects were not selected for any
      sleep-related complaint. In addition to standard measures, studies included
      monitoring of end-tidal carbon dioxide (n = 22), and esophageal pressure (n =
      20). RESULTS: The rate of apneas and hypopneas per hour of sleep was >5 in 20
      subjects (80%; 95% CI, 64% to 96%), minimum oxygen saturation was <90% in 10
      subjects, maximum negative esophageal pressure ranged from -13 to -65 cm H2O, and
      maximum end-tidal carbon dioxide was > or =50 mm Hg in eight subjects. The eight
      subjects with active (versus inactive) CH at the time of study had higher maximum
      end-tidal carbon dioxide levels (50 +/- 3 versus 44 +/- 5 mm Hg; p = 0.0007).
      More severe oxygen desaturation was associated with reports that CH typically
      occurred in the first half of the nocturnal sleep period (p = 0.008).
      CONCLUSIONS: SDB occurred in the majority of patients with CH. Evaluation of a
      patient with CH should include consideration that SDB may be present.

PMID- 10881258
TI  - Multiple sclerosis and antecedent infections: a case-control study.
AB  - OBJECTIVES: To determine whether there is an excess of respiratory tract
      infections in the 5-week, 3-month, and 12-month periods before MS symptom onset
      and if there is an association between MS and a history of infectious
      mononucleosis (IM). BACKGROUND: The etiology of MS remains unknown, but infection
      is frequently suggested as a putative etiologic agent. Epidemiologic studies have
      produced inconsistent evidence for an etiologic role of respiratory tract
      infections (RTI) and IM in MS. METHODS: The authors performed a case-control
      study using the General Practice Research Database from the United Kingdom. There
      were 225 subjects with definite or probable MS, and 900 controls matched for age,
      sex, and physician practice. Using computerized patient records, the authors
      compared the mean rates of RTI per patient in the 5-week, 3-month, and 12-month
      periods before the date of onset of the first symptoms compatible with MS (index
      date). They also compared histories of IM. RESULTS: In all periods, an increased
      frequency of RTI was associated with a significantly increased risk of MS. A
      history of IM was associated with greater than five times the risk of MS (OR =
      5.5 [95% CI 1.5 to 19.7]). CONCLUSIONS: These results support an association
      between a history of IM and subsequent MS. Respiratory tract infections may
      precipitate disease onset.

PMID- 10881259
TI  - Long-term outcome in patients with Guillain-Barre syndrome requiring mechanical
      ventilation.
AB  - OBJECTIVE: To analyze long-term recovery and predictors of outcome in patients
      with Guillain-Barre syndrome (GBS) requiring mechanical ventilation. METHODS: The
      clinical and electrophysiologic data of 114 patients with GBS admitted to the
      intensive care unit between 1976 and 1996 (60 mechanically ventilated, 54
      nonventilated) were reviewed. Functional disability and predictors of outcome
      were determined at 1 year and at maximal recovery using the Hughes scale. Good
      outcome was defined as ability to ambulate without assistance; poor outcome was
      defined as inability to ambulate independently. RESULTS: Mechanical ventilation
      was required in 81% of patients with a poor outcome. Mortality was 20% in
      patients ventilated for GBS. However, ventilated patients who survived did well,
      with 79% eventually regaining independent ambulation. Nineteen percent of
      patients improved at least one functional grade beyond 1 year. Univariate
      predictors of poor maximal recovery in ventilated GBS patients were increased age
      (p < 0.001)), upper limb paralysis (p = 0.004), duration of ventilation (p =
      0.006), and delay of more than 2 days to transfer to a tertiary center (p <
      0.001). However, only age (OR 1.99, p = 0.004) and delayed transfer (OR 19.8, p =
      0.002) were independently predictive of poor outcome on multivariate analysis.
      CONCLUSION: Mechanically ventilated patients constitute the majority of GBS
      patients with a poor outcome, and mortality remains substantial in this subgroup
      (20%). Although recovery from severe GBS may be prolonged, most survivors regain
      independent ambulation.

PMID- 10881260
TI  - Facial frequency manipulation normalizes face discrimination in AD.
AB  - People with AD have deficient contrast sensitivity and impaired face
      discrimination. The authors presented photographs of unfamiliar faces of three
      different sizes to enhance the low, middle, or high facial frequency information
      (cycles per face). Patients with AD demonstrated normal discrimination of small
      faces only, indicating that impaired contrast sensitivity at low facial
      frequencies contributes to their poor face discrimination.

PMID- 10881261
TI  - Apolipoprotein E allele-dependent antioxidant activity in brains with Alzheimer's
      disease.
AB  - Thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation,
      were assayed in postmortem brain. Basal TBARS levels were increased and oxidative
      stimulation produced more TBARS in AD relative to control brains. In addition,
      apolipoprotein E isoforms showed differing antioxidant activities, with E2 > E3 >
      E4, suggesting that the lowest antioxidant activity of E4 could contribute to its
      association with AD.

PMID- 10881263
TI  - Ataxia, deafness, leukodystrophy: inherited disorder of the white matter in three
      related patients.
AB  - The authors report three related patients, two girls and a boy, presenting a
      distinctive clinical phenotype characterized by early-onset, slowly progressive
      ataxia. Subsequently these patients experienced sensorineural deafness, resulting
      in complete hearing loss by the age of 12 years, and exhibited leukodystrophy on
      brain MRI. There was no mental deterioration. An extensive neurometabolic
      assessment failed to detect any anomalies in the three patients. The patients
      originated from a large consanguineous family in southern Italy (Calabria), with
      a pedigree that was traced back five generations. The disease's pattern of
      transmission suggests an autosomal recessive trait.

PMID- 10881262
TI  - Unique origin and specific ethnic distribution of the Friedreich ataxia GAA
      expansion.
AB  - The GAA triplet repeat expansion that causes Friedreich ataxia is found only in
      individuals of European, North African, Middle Eastern, or Indian origin (Indo
      European and Afro-Asiatic speakers). Analysis of normal alleles of the GAA repeat
      and of closely linked markers suggests that expansions arose through a unique two
      step process. A major implication of these findings is that Friedreich ataxia may
      not exist among sub-Saharan Africans, Amerindians, and people from China, Japan,
      and Southeast Asia.

PMID- 10881264
TI  - Cardiac complications in pediatric patients on the ketogenic diet.
AB  - Cardiac complications of the ketogenic diet, in the absence of selenium
      deficiency, have not been reported. Twenty patients on the ketogenic diet at one
      institution were investigated. Prolonged QT interval (QTc) was found in 3
      patients (15%). There was a significant correlation between prolonged QTc and
      both low serum bicarbonate and high beta-hydroxybutyrate. In addition, three
      patients had evidence of cardiac chamber enlargement. One patient with severe
      dilated cardiomyopathy and prolonged QTc normalized when the diet was
      discontinued.

PMID- 10881265
TI  - Magnetization transfer and diffusion-weighted imaging in nocturnal frontal lobe
      epilepsy.
AB  - The authors assessed the presence of brain abnormalities in 21 patients with
      nocturnal frontal lobe epilepsy (NFLE), using magnetization transfer ratio (MTR)
      and mean diffusivity (;D) histograms. Compared with healthy volunteers and
      patients with idiopathic generalized epilepsy, patients with NFLE had lower MTR
      (p = 0.002 and 0.01) and;D (p = 0.03 and 0.04) histogram peak heights. Subtle and
      widespread abnormalities related to intra- and extracellular distribution and
      motion of water are detectable in the brains of patients with NFLE.

PMID- 10881266
TI  - The relation between aneurysm size and outcome in patients with subarachnoid
      hemorrhage.
AB  - The balance of risks of treatment for unruptured aneurysms might change if the
      prognosis after rupture depends on the size of the aneurysm. In a prospective
      series of patients with subarachnoid hemorrhage in whom aneurysmal size was
      measured by CT angiography performed on admission, poor outcome occurred more
      often in patients with large (> or =10 mm) aneurysms (63%) than in patients with
      small (<10 mm) aneurysms (41%; RR = 1.5; 95% CI 1.0 to 2.2). The relative risk
      remained essentially the same after adjustment for age, gender, location of the
      aneurysm, and amount of cisternal blood.

PMID- 10881267
TI  - Apraxic agraphia due to thalamic infarction.
AB  - The authors report a patient of pure apraxic agraphia with normal praxis due to
      left thalamic infarction. 15O-gas-PET showed reduced oxygen metabolism in the
      left thalamus and the left dorsolateral premotor area, while MRI and 11C
      fulumazenil-PET showed no remarkable lesions in the frontal cortex. The patient's
      word imaging remained normal. The authors hypothesize that thalamic destruction
      causes pure apraxic agraphia by exerting a remote effect on left dorsolateral
      premotor area and blocking somewhere between graphemic area and motor
      programming.

PMID- 10881268
TI  - Unilateral pure thalamic asterixis: clinical, electromyographic, and topographic
      patterns.
AB  - Eleven patients (nine with infarctions and two with primary hematomas) with
      isolated thalamic lesions and contralateral asterixis were examined using a
      standard electromyographic and neuroimaging protocol. Asterixis was a short
      duration phenomenon associated with a hemiataxia hypesthesia syndrome in all
      patients. Electromechanical synchronization was constant for the two silent
      period types. The anatomic data strongly suggest that ventral lateral or lateral
      posterior thalamus are concerned in the pathophysiology of thalamic asterixis.

PMID- 10881269
TI  - Thalamic stimulation for the treatment of midline tremors in essential tremor
      patients.
AB  - The authors prospectively collected unblinded data from 27 consecutive patients
      following thalamic stimulation. A significant reduction of midline tremor was
      achieved after unilateral surgery, but a staged contralateral surgery had an
      additional effect. A subgroup analysis showed significant beneficial effects for
      head, voice, tongue, and face tremor. The most frequent reversible side effects
      were disequilibrium, dysarthria, and paresthesias. We observed more pulse
      generator adjustments for speech problems in the bilaterally implanted group.

PMID- 10881270
TI  - Deafness associated with abuse of hydrocodone/acetaminophen.

PMID- 10881271
TI  - Subdural hematoma during low-dose ACTH therapy in patients with west syndrome.

PMID- 10881272
TI  - Celiac disease and idiopathic cerebellar ataxia.

PMID- 10881273
TI  - Heart rate does not decrease after right hemispheric amobarbital injection.

PMID- 10881274
TI  - Multiple cranial nerve enhancement in early infantile Krabbe's disease.

PMID- 10881275
TI  - Testing for serum IgM binding to GM1 ganglioside in clinical practice.

PMID- 10881276
TI  - Brachial amyotrophic diplegia: a slowly progressive motor neuron disorder.

PMID- 10881277
TI  - Cognitive consequences of coexisting temporal lobe developmental malformations
      and hippocampal sclerosis.

PMID- 10881278
TI  - The effect of apoE on dementia is not through atherosclerosis: the Rotterdam
      study.

PMID- 10881279
TI  - Morphogenesis and distribution of Trichostrongylus retortaeformis in the
      intestine of the rabbit.
AB  - The morphogenesis and the distribution along the digestive tract of
      Trichostrongylus retortaeformis(Zeder, 1800) (Nematoda) were studied in detail in
      one of its natural hosts, Oryctolagus cuniculus. Worm-free rabbits were each
      infected with T. retortaeformis larvae and were killed at 12 h post-infection
      (HPI) and on each day from 1 to 15 days post-infection (DPI). The distribution of
      worm populations along the small intestine was assessed. At the different dates
      of infection, more than 80% of the population was recovered from the first third
      of the intestine with more than 50% occurring in the first 30 cm. For each date,
      morphological descriptions of the different stages of the life cycle were also
      provided. In addition, adult worms collected from naturally infected rabbits from
      France were redescribed.

PMID- 10881280
TI  - A cytogenetic study on the rodent tapeworm Rodentolepis myoxi.
AB  - The karyotype of glirid tapeworm Rodentolepis myoxi (Rudolphi, 1819) (Cestoda:
      Hymenolepididae) comprises six pairs of small bi-armed chromosomes (2n = 12). All
      pairs of chromosomes possess uniform morphology, i.e. metacentric, submetacentric
      or meta-submetacentric types of structures. The formula of the karyotype
      structure is n = 2m + 1m-sm + 3sm. The absolute chromosome length ranges from
      3.78 to 2.00 microm. The mean total length of the haploid complement is 15. 98
      microm. The first pair (group A) is the largest, pairs 2 and 3 can be grouped
      into group B while pairs 4-6 are smaller and can be classified as group C. The
      number of chromosomes of R. myoxi is the same for the congeneric species,
      however, karyological characteristics differ from all recently known karyotypes
      of rodent hymenolepidids.

PMID- 10881281
TI  - Cystacanths of Bolbosoma vasculosum in the black scabbard fish Aphanopus carbo,
      oceanic horse mackerel Trachurus picturatus and common dolphin Delphinus delphis
      from Madeira, Portugal.
AB  - Cystacanths of the acanthocephalan, Bolbosoma vasculosum Rudolphi 1819, were
      found to be encapsulated in the connective tissues of the viscera of the black
      scabbard fish, Aphanopus carbo and oceanic horse mackerel, Trachurus
      picturatusfrom Madeira, Atlantic Ocean. Juvenile worms were obtained from the
      intestine of a stranded common dolphin, Delphinus delphis, also from Madeira.
      Cystacanths were 11-15 mm long, with a proboscis of 18-19 longitudinal rows,
      eight hooks per row, and two sets of trunk spines. Overall, the morphology and
      dimensions of the proboscis, neck and trunk corresponded to previous
      descriptions. Scanning electron microscopy of the proboscis structures and trunk
      spines is provided for the first time. The prevalence of B. vasculosum in A.
      carbo increased with fish length. There were no statistical differences in the
      prevalence and intensity of infection between seasons. The intensity of infection
      was similar for male and female fishes, but there were significant differences in
      relation to length, longer fishes having heavier infections. Aphanopus carbo from
      Madeira represents a new host record and a new geographic location for B.
      vasculosum.

PMID- 10881282
TI  - The distribution of the introduced tapeworm Bothriocephalus acheilognathi in
      Australian freshwater fishes.
AB  - Native and exotic fishes were collected from 29 sites across coastal and inland
      New South Wales, Queensland and Victoria, using a range of techniques, to infer
      the distribution of Bothriocephalus acheilognathi (Cestoda: Pseudophyllidea) and
      the host species in which it occurs. The distribution of B. acheilognathi was
      determined by that of its principal host, carp, Cyprinus carpio; it did not occur
      at sites where carp were not present. The parasite was recorded from all native
      fish species where the sample size exceeded 30 and which were collected
      sympatrically with carp: Hypseleotris klunzingeri, Hypseleotris sp. 4,
      Hypseleotris sp. 5, Phylipnodon grandiceps and Retropinna semoni. Bothriocephalus
      acheilognathi was also recorded from the exotic fishes Gambusia holbrooki and
      Carassius auratus. Hypseleotris sp. 4, Hypseleotris sp. 5, P. grandiceps, R.
      semoni and C. auratus are new host records. The parasite was not recorded from
      any sites in coastal drainages. The only carp population examined from a coastal
      drainage (Albert River, south-east Queensland) was also free of infection; those
      fish had a parasite fauna distinct from that of carp in inland drainages and may
      represent a separate introduction event. Bothriocephalus acheilognathi has
      apparently spread along with its carp hosts and is so far restricted to the
      Murray-Darling Basin. The low host specificity of this parasite is cause for
      concern given the threatened or endangered nature of some Australian native
      freshwater fish species. A revised list of definitive hosts of B. acheilognathiis
      presented.

PMID- 10881283
TI  - Rodents as reservoir hosts in the transmission of Schistosoma mansoni in Richard
      Toll, Senegal, West Africa.
AB  - More than 2000 animals belonging to six different rodent species and one
      insectivore species were examined for infection with schistosomes in the region
      of Richard-Toll, Senegal. Two murid rodents, Arvicanthis niloticus and Mastomys
      huberti, were found infected with Schistosoma mansoni. Prevalences were about 5%
      for both rodent species with a mean worm burden of about 20 worms per host. The
      sex-ratios of S. mansoni worms were always biased towards males. Prevalences and
      worm burdens, although similar in both male and female rodents, increased
      significantly with age. The highest prevalences and worm burdens were found near
      habitations and decreased significantly with the distance from the town of
      Richard-Toll. Eggs were also observed in the liver and faeces of the two
      naturally infected rodent species. The results suggest that rodents participate
      in the transmission of intestinal schistosomiasis in Richard-Toll but the human
      population is the main source of infection. The genetic resemblance between human
      and murine isolates of S. mansoni suggests that further epidemiological studies
      are needed in this region of Senegal.

PMID- 10881285
TI  - Occurrence and distribution of the entomopathogenic nematodes Steinernema spp.
      and Heterorhabditis indica in Indonesia.
AB  - Soil samples from 79 sites on five islands of Indonesia were baited with insects
      for the recovery of entomopathogenic nematodes. Heterorhabditis and Steinernema
      were equally prevalent, and were recovered from 11.7% of samples representing
      20.3% of sites sampled. Both genera were recovered from coastal sites only.
      Entomopathogenic nematodes were more prevalent on the Moluccan islands of Ambon
      and Seram than on Java or Bali. They were not detected on Sulawesi, where non
      coastal sites only were sampled. RFLP analysis was used in the identification of
      nematode isolates. Heterorhabditis indica was the only heterorhabditid
      identified. Two RFLP types of Steinernema were identified.

PMID- 10881284
TI  - The use of zeolites as slow release anthelmintic carriers.
AB  - This work examines the ability of commercial zeolite Y to act as a slow release
      agent for a number of anthelmintic drugs. Administration to rats, dosed with
      Nippostrongylus brasiliensis, of pyrantel and/or fenbendazole and pigs, dosed
      with Ascaris and Oesophagostomum, of dichlorvos (DDVP) loaded onto zeolite Y was
      more successful in killing adult worms than administration of the pure drug
      alone. The zeolite Y was used as supplied for initial studies and then later
      dealuminated for further studies. The drug loadings were monitored by thermal
      analysis and the loaded zeolites were used in several field trials. The results
      indicate that zeolite Y is a suitable vehicle for the slow release of some
      anthelmintics. The slow release of drug from the zeolite matrix improved its
      efficacy.

PMID- 10881286
TI  - 'Cebiche'--a potential source of human anisakiasis in Mexico?
AB  - Five fish species used for preparation of a popular dish (cebiche) made with raw
      fish flesh in Mexico were obtained from five localities of the coast of Yucatan.
      Lutjanus synagris, Gerres cinereus, Sphyraena barracuda, Epinephelus morio and
      Haemulon plumieriwere examined for the presence of larvae of anisakid nematodes,
      causative agents of human anisakiasis. The nematode Pseudoterranova sp. was found
      in E. morio and S. barracuda with a total prevalence of 83% and 6.5 +/- 6.2 worms
      per fish for E. morio, and a prevalence of 33% and 10.2 +/- 30.0 worms per fish
      for S. barracuda. Contracaecumsp. was found to infect G. cinereus with a
      prevalence of 57% and 7.6 +/- 11.4 worms per fish. The relatively high prevalence
      of Pseudoterranova sp. indicates that this parasite is a potential causal agent
      of anisakiasis on the coast of Yucatan. Although all larvae were found only in
      the mesentery of the fish host, their importance as a potential source of human
      infection cannot be excluded as larval migration to the muscles in dead fish is
      possible.

PMID- 10881287
TI  - Acquired resistance in rainbow trout against Gyrodactylus derjavini.
AB  - Investigations were conducted on the host response in rainbow trout and the
      associated changes in mucous cell density during infection with the skin
      monogenean Gyrodactylus derjavini. Parasite populations increased on all naive
      hosts and peaked 4-5 weeks p.i. after which infection levels decreased.
      Introduction of naive fish into responding host populations resulted in heavy
      infections of the naive fish, whereas parasite expulsion continued in the
      responding host groups showing an acquired, non-sterile immunity. This non
      sterile immunity lasted at least a month as these hosts were refractory to
      reinfection despite being exposed to a high infection pressure. Mucous cell
      hyperplasia was seen in some groups during the intermediary phase of infection,
      but at the termination of the study a significant depletion was evident. Passive
      immunization of naive host (with sera from immune hosts) did not confer
      protection. This indicates differences between host responses to G. derjavini
      compared to responses against other pathogens where such a passive immunity has
      been described.

PMID- 10881288
TI  - The occurrence of two opecoeliid digeneans in Mullus barbatus and M. surmuletus
      from the Spanish south-eastern Mediterranean.
AB  - The infection by Opecoeloides furcatus and Poracanthium furcatum (Opecoeliidae)
      was studied in 121 Mullus barbatus and 113 M. surmuletus collected from the
      Spanish south-eastern Mediterranean. The prevalence of infection was most
      frequent in M. surmuletus with values of 81.42% for O. furcatus and 38.05% for P.
      furcatum. In M. barbatus the prevalences of O. furcatus and P. furcatum were
      54.54% and 14.88% respectively. Statistically significant differences were found
      between the infection of the two hosts with P. furcatum. No significant
      differences in worm burdens could be attributable to host size or to seasonal
      changes, although a lower infection of M. barbatus by O. furcatus occurred in the
      autumn. Furthermore, the electrophoretic mobility of the enzyme malic
      dehydrogenase (MDH) was also studied and both digeneans presented different
      patterns, corresponding in both cases to homozygotic genotypes.

PMID- 10881289
TI  - The life cycle and transmission dynamics of the larval stages of Hypoderaeum
      conoideum.
AB  - The morphology of the different larval stages and life cycle of Hypoderaeum
      conoideum (Trematoda: Echinostomatidae) are described. The freshwater snail
      species Lymnaea peregra (Gastropoda: Lymnaeidae) serves as the natural first
      intermediate host and this and L. corvus serve as experimental first intermediate
      hosts. These and other freshwater snails, such as Physella acuta and Gyraulus
      chinensis, in turn serve as second intermediate hosts. Adult worms were obtained
      from chicks and ducks, but not from rats, mice and golden hamsters. The
      morphology of the larval stages is compared with previous work on H. conoideum.
      Several aspects of the biology of the life history stages are described with
      emphasis on the transmission dynamics of the free-living stages. Differential
      suitability of the snail species that may act as first and/or second intermediate
      hosts is studied and discussed.

PMID- 10881290
TI  - Survey of Spirometra erinaceieuropaei in frogs in Taiwan and its experimental
      infection in cats.
AB  - Eighteen of 56 (32.1%) wild Rana limnocharis from central and south Taiwan were
      found to contain plerocercoids of Spirometra erinaceieuropaei. This is the first
      report of S. erinaceieuropaei infections in frogs in Taiwan, with the
      plerocercoids being recovered from the thigh and back muscles or under the skin.
      Other species of frogs examined, including nine wild R. latouchii, one wild
      Buergeria robustus and 110 cultured R. rugulosa were free of infection. The
      plerocercoids were orally inoculated into four cats; three of which were each
      given a single plerocercoid and one a dose of three plerocercoids. Daily faecal
      examination showed that two cats started shedding eggs of S. erinaceieuropaei on
      day 8 postinfection (PI) and the other two on day 10 PI. The highest eggs per
      gram and eggs per day for a single worm was found to be 428,000 and 14,416,000
      respectively. Only the cat inoculated with three plerocercoids shed proglottids
      in its faeces during the 2 month observation period.

PMID- 10881291
TI  - Molecular evidence for the presence of a G7 genotype of Echinococcus granulosus
      in Slovakia.
AB  - Variability in Echinococcus granulosus is very important epidemiologically since
      strain characteristics may influence local patterns of transmission of hydatid
      disease. To classify the genotype presented in pig protoscoleces of the Slovak
      territory, a DNA-based approach has been used. Nucleotide sequences for a 471 bp
      region of the mitochondrial NADH dehydrogenase 1 (ND1) gene revealed a
      substantial affinity of isolates examined to the G7 genotype. Only a 0.9-3.4%
      sequence variation was recorded for E. granulosus samples compared with the
      reference G7 variant. To distinguish between G7 and G9 genotypes not differing in
      ND1 sequences, isolates were additionally examined by PCR-RFLP analysis of the
      nuclear ITS1 region. The resulting two-banded pattern is characteristic for the
      G7 strain. The data presented thus provides the first explicit evidence of the G7
      genotype in the Slovak region.

PMID- 10881293
TI  - Shots in the dark?

PMID- 10881292
TI  - Localization of a 24-kDa collagenase in the Gymnorhynchus gigas plerocercoid.
AB  - A 24-kDa collagenase was localized in the Gymnorhynchus gigas plerocercoid
      immunohistochemically by peroxidase complex staining using polyclonal antibodies
      from NMRI mouse sera immunized with purified enzyme. Immunoreactivity was
      determined at different parts of the body (scolex, vesicle and caudal region) and
      mainly localized in microtriches and parenchymal tissues of the scolex and
      vesicle. These results, along with the absence of the enzyme in the plerocercoid
      excretion-secretion products, suggest that the 24-kDa collagenase is produced by
      parenchymal cells in the anterior region and transported to the outer regions of
      the worm It is possible that the enzyme plays an important role in degrading
      parasite tissues during the moulting process.

PMID- 10881294
TI  - Shots in the dark?

PMID- 10881295
TI  - Explaining ether

PMID- 10881296
TI  - Boomerang effect. Balloon data confirm the big bang--and challenge it, too

PMID- 10881298
TI  - Fire in the sky

PMID- 10881297
TI  - Age breakers. Rupturing the body's sugar-protein bonds might turn back the clock.

PMID- 10881299
TI  - The geography of death.

PMID- 10881300
TI  - Diseased passage.

PMID- 10881301
TI  - Raging rivers of rock

PMID- 10881302
TI  - The search for extreme life.

PMID- 10881303
TI  - Scar no more.

PMID- 10881304
TI  - From vitamin E to Z-plasty. Plastic surgeons have more than one trick to remove a
      scar

PMID- 10881305
TI  - Searching for extraterrestrials. Where are they?

PMID- 10881307
TI  - Searching for extraterrestrials. Intragalactically speaking.

PMID- 10881306
TI  - Searching for extraterrestrials. Where they could hide.

PMID- 10881308
TI  - The human genome business today.

PMID- 10881309
TI  - The bioinformatics gold rush.

PMID- 10881311
TI  - The Large Hadron Collider

PMID- 10881310
TI  - Beyond the human genome.

PMID- 10881313
TI  - The revolutionary bridges of Robert Maillart

PMID- 10881312
TI  - Darwin's influence on modern thought.

PMID- 10881314
TI  - The killing lakes.

PMID- 10881315
TI  - Knotting ventured...

PMID- 10881316
TI  - [Transfer of skin conductance responses through stimulus equivalence classes].
AB  - This study investigated the transfer of classically conditioned skin conductance
      responses through stimulus equivalence classes. Fourteen subjects were taught 4
      stimulus relations, A1-->B1, A1-->C1, A2-->B2, and A2-->C2 through matching-to
      sample training. In subsequent matching-to-sample tests, 13 subjects demonstrated
      the formation of two stimulus equivalence classes, "A1, B1, and C1" and "A2, B2,
      and C2." They then received differential conditioning, in which Stimulus B1 was
      followed by electric shocks, while B2 was not followed by the shocks. Subsequent
      transfer tests revealed that skin conductance responses for Stimulus C1 were
      greater than those for C2, suggesting the transfer of conditioned responses
      through the stimulus equivalence classes.

PMID- 10881317
TI  - [Psychological complexity of the figures and properties of retention in visual
      short-term memory].
AB  - We investigated how the physical variables of complex figures had effects on
      psychological complexity and recognition of complex figures. Complexity was
      objectively defined by the amount of convex parts and Perimeter/square root of
      Area (P/square root of A), which varied with both the number of convex parts and
      the length of one convex part. In complexity judgments the results showed that
      the judged complexity was not well predicted by P/square root of A, and that the
      amount of convex parts rather than P/square root of A had much influence on the
      judged complexity. In a recognition experiment, the results showed that
      performance was dependent on both the number of convex parts and the length of
      one convex part when P/square root of A was held constant. When P/square root of
      A was low and constant, performance tended to deteriorate with increasing the
      amount of convex parts. But when P/square root of A was high and constant,
      performance peaked at a convex parts value of 8, and deteriorated at higher or
      lower values of convex parts. The results indicated that both the number of
      convex parts and the length of one convex part were effective in deteriorating
      retention in visual short-term memory, and that P/square root of A had indirect
      influence on performance.

PMID- 10881318
TI  - [Japanese Kana word recognition].
AB  - Three experiments were conducted to investigate letter migration in Japanese Kana
      word recognition. The participants were presented two brief masked "source" words
      (e.g., [symbol: see text]) each made up of two components (letters), followed by
      a "probe" word (e.g., [symbol: see text]). The probe word in the critical trials
      was a blend of two letters, one each from the two source words. The task was to
      decide whether the probe was one of the source words. The results indicated that
      the proportion of false positive responses depends on consistency of positions of
      the components in probe word with those in source words set (global consistency),
      and on consistency between the first letter of source and probe words (left local
      consistency). The results also showed that statistical properties of letters,
      i.e., the number of companions (adjoining letters) of a letter influenced the
      false response. These results were compared with those with a Kanji word
      suggesting that knowledge of conjunctive properties of word-components affects
      word recognition irrespective of scripts.

PMID- 10881319
TI  - [Can three-year old children take spatial perspectives?: an approach with the
      'face rotation task'].
AB  - Spatial perspective taking ability of two-year-six-month to four-year-five-month
      old children was investigated, using a newly devised task named the 'Face
      Rotation Task.' In the task one of the two eyes in the face stimulus, which had
      been rotated 90, 180, or 270 degrees from the upright position, was highlighted
      and a buzzer sound was simultaneously presented. The subjects were asked to
      memorize the combination of the highlighted eye and the sound. When the face
      stimulus was set back to the normal upright position, the buzzer sound was
      presented and the subjects were asked to look or point at the position of the
      expected highlighting eye. Children over 3.5 years performed significantly better
      than chance expectation. The mental strategy employed by the children was also
      investigated using a modified Face Rotation Task. The result indicated that the
      mental strategy was perspective taking. The implications of these results were
      discussed in terms of the appropriate meaning of perspective taking ability.

PMID- 10881320
TI  - [Semantic processing of words in selective listening: an examination using
      recognition tests and event-related brain potentials].
AB  - Two experiments were conducted to investigate the degree of semantic processing
      for unattended words. In a dichotic listening task, each participant was required
      to attend selectively to either a word sequence in one ear or a speech passage in
      the opposite ear. The selective listening was confirmed by attenuated P1-N1 and
      N400 waves of the event-related brain potential to unattended words. The N400
      attenuation with semantic priming was observed only for attended words. In a
      following recognition test with a booklet and auditory presentation, the
      percentage of false alarms for "new" words (or lures) semantically related to
      "old" words was higher when the "old" words were attended in selective listening
      than when unattended. These findings suggest that selective attention can act
      before and/or at a level of semantic processing.

PMID- 10881321
TI  - [The factor structure of relief feeling in situations: relief from tension and
      calmness and relaxation].
AB  - The purpose of this study was to investigate the subjective emotional states of
      'feeling of relief (ANDO-KAN),' In Study 1, an open-ended questionnaire, with 64
      subjects, found 127 concrete situations, in which they experienced feeling of
      relief. In Study 2, 182 subjects completed a questionnaire, which measured
      subjective arousal during the time they experienced relief. Results indicated
      that two distinct type of situation were related to feeling of relief: situation
      of relief from tension and that of calmness and relaxation. Tension was
      associated with the former, but not the latter; however, general deactivation
      characterized both types of situation. We concluded that feeling of relief
      probably consisted of two discrete subjective emotional states, and that they
      could be explained in terms of distinct arousal states.

PMID- 10881322
TI  - [Effect of concreteness of target words on verbal working memory: an evaluation
      using Japanese version of reading span test].
AB  - Effects of concreteness and representation mode (kanji/hiragana) of target words
      on working memory during reading was tested using Japanese version of reading
      span test (RST), developed by Osaka and Osaka (1994). Concreteness and
      familiarity of target words and difficulty of sentences were carefully
      controlled. The words with high concreteness resulted in significantly higher RST
      scores, which suggests the high efficiency of working memory in processing these
      words. The results suggest that high concrete noun-words associated with visual
      clues consume less working memory capacity during reading. The effect of
      representation mode is different between subjects with high-RST and low-RST
      scores. Characteristic of the high concrete words that may be responsible for the
      effectiveness of processing are discussed.

PMID- 10881323
TI  - [Influences of gender conception on gender-role attitudes and preference].
AB  - This study investigated the influences of age and length of education on gender
      conception, and the influences in turn of the conception on gender-role attitudes
      and preference, with multiple regression analysis. Of a random sample of 1,500
      Tokyo residents, aged between 20 and 60, 342 women and 313 men completed a
      questionnaire concerning their views of gender. The questions were structured to
      measure their agreement to gender-stereotyped opinions and behaviors. Results
      were as follows: (1) The older both men and women were, the more rigid their
      gender conception was. (2) The longer the respondent's education was, the more
      flexible their gender conception was. (3) These tendencies were stronger for
      women than men. (4) Pass analysis indicated that age, education, and parents'
      gender-typed expectation affected gender conception, which in turn influenced
      gender-role attitudes, and also that gender-roles were chosen on the basis of
      gender-role attitudes. It was concluded that age and length of education affected
      gender-role attitudes and preference, through gender conception in the context of
      gender schematic processing.

PMID- 10881324
TI  - [Fish nutrition. Brief review for the practitioner regarding food and ornamental
      fish].
AB  - In behalf of the practitioner a short survey is given about nutrition of fish and
      shrimps. Interrelations between fish development and influences by their water
      ecosystem concerning temperature, mineral and gas levels, waterflow et cetera
      together with the supply of food are mentioned. Further comments are given about
      common nutritional needs of different species in connection with growth,
      bodyweight et cetera and purpose of fishkeeping for instance for consumption,
      reproduction or ornamentally in different systems from aquarium to lagoon. More
      specifically feed formulation from raw materials to complete diets and
      nutritional analyses in respect to allowances for maintenance and growth are
      discussed. Data about fresh- and saltwater species from tropical to arctic
      circumstances mentioning trout, salmon, catfish, carp, sea bass, shrimp et cetera
      are given. Some remarks about manufacturing, and application of complete compound
      feeds are added to the survey. In behalf of further study or for enhancement of
      knowledge a number of books are recommended in a list of references.

PMID- 10881325
TI  - A. McGehee Harvey and the American Clinical and Climatological Association.

PMID- 10881326
TI  - Edward W. Hook, Jr. 1924-1998.

PMID- 10881327
TI  - R. Carmichael Tilghman 1904-1999.

PMID- 10881328
TI  - A challenge for the twenty-first century: multicultural parity in medicine.

PMID- 10881329
TI  - Influence of myocarditis on left ventricular function.

PMID- 10881330
TI  - Familial polycythemia due to truncations of the erythropoietin receptor.
AB  - We studied a kindred with dominantly inherited familial erythrocytosis associated
      with heterozygosity for a deletion of seven nucleotides in exon 8 of the EpoR
      gene resulting in an EpoR peptide that is truncated by 59 amino acids in its C
      terminal intracytoplasmic signal transduction domain. A seven basepair direct
      repeat sequence is present in the normal EpoR gene at the site of this mutation,
      consistent with the slipped mispairing model for the generation of short
      deletions during DNA replication. Hypersensitivity to erythropoietin of primary
      erythroid progenitors from an affected individual was observed in in vitro
      cultures of peripheral blood mononuclear cells, as indicated by the growth, at
      suboptimal concentrations of added Epo, of more numerous and larger BFU-E-derived
      erythroid cell colonies compared to those obtained from a normal control subject.
      To study mutant EpoR function, the cDNA encoding the mutant EpoR was stably
      transfected into murine growth factor (IL-3)-dependent 32D tissue culture cells.
      In proliferation assays, cells expressing the mutant EpoR displayed 5 to 10-fold
      increased sensitivity to Epo compared to cells expressing similar numbers of the
      wild type EpoR. In addition, the cells transfected with the mutant truncated
      receptor demonstrated prolonged activity of Jak2 kinase and Stat5 activity,
      molecules that mediate signal transduction by the EpoR.

PMID- 10881331
TI  - Interleukin-5, a therapeutic target in allergic inflammation.

PMID- 10881333
TI  - From hot dogs to CD8+ T cells: Listeria monocytogenes.

PMID- 10881332
TI  - Carbon monoxide detection and biological investigations.
AB  - Even though the heme degradation pathway consists of only two reactions, it and
      its major enzyme (i.e. HO), nonetheless, impact other processes not only through
      the removal of excess heme, but also through the production of several
      metabolically active compounds. Thus CO and biliverdin along with reactive iron,
      Fe2, are the primordial products of this ancient, highly conserved reaction. That
      every component of the heme catabolic pathway is directly or indirectly related
      to other reactions involving oxygen or light is, perhaps, no accident of nature.
      That a fundamentally destructive event can be linked with a multiplicity of
      synthetic events and various biological effects, depending on the timing and
      location of the HO activity, is testament to the economy and the ultimate beauty
      of nature. Furthermore, the interaction of the heme catabolic pathway with that
      of the NOS system may lead to even more exciting avenues of research. It may be
      shown that the integrity of the heme catabolic pathway, which is ever present and
      plays a role in every tissue, is central to the existence of most complex
      organisms.

PMID- 10881334
TI  - On being paid not to work for the men of impressive but easy affairs.
AB  - I hide behind my limited presentation time to retreat from offering answers to
      this dilemma, save to cite one example to illustrate that knowledge workers are
      not politically hopeless. In response to a severe need, investigators mobilized
      in the last 5 years to advocate for increased federal funding for research. The
      succeeded. Many deans, department chairs, and other managers, including the NEJM
      editors, viewed this project as unlikely to succeed and not worthy of their
      aggressive promotion. Perhaps this example suggests that knowledge workers should
      sometimes work for pay to solve their problems. Please see in REFERENCES my
      comments on certain cited papers. Thank you for your attention and welcome
      discussion.

PMID- 10881336
TI  - HIV/AIDS managed care program.
AB  - Approximately one-half of all patients with HIV infection who are under care have
      Medicaid as the third party payor. Unlike Medicare, Medicaid is a state-specific
      program that has huge variations in reimbursement strategies. Multiple studies
      have shown that care for persons with AIDS is about $20,000/year, but
      reimbursement through various state Medicaid programs varies about $100/m/m to
      $2800/m/m despite the fact that expectations for care are identical. Hopkins has
      a major commitment to persons with HIV infection with a program that now includes
      30 faculty members and a support staff of 170. With the introduction of mandatory
      managed care for Medicaid recipients in July, 1997, we were confronted with the
      issue of substantial downsizing with abandonment of over half of our patients, or
      learning the transition to managed care. This has been a steep learning curve
      involving negotiations with the state Medicaid office, reorganization of our
      clinic, careful scrutiny of our database regarding resource utilization and cost,
      education of providers, and longitudinal collection of new information and
      integration of the rapid changes in the field. In the process of this transition,
      we learned that there are precious few resources to provide guidance and that
      there is a perceived need for assistance by HIV providers throughout the country.
      Consequently, we have now established the "HIV Managed Care Network" with
      substantial funding from diverse sources to support education, data collection,
      and public policy review. It is premature to evaluate performance since most of
      these activities have just begun, but we expect that this Network will serve as a
      demonstration model for methods to deal with chronic diseases under managed care.

PMID- 10881335
TI  - Jeremiah Metzger Lecture. Targeted cancer therapy.
AB  - I have reviewed here and elsewhere the preclinical data and the clinical trials
      which have demonstrated the efficacy of therapy with monoclonal antibodies that
      block activation of receptors for growth factors (12). Herceptin is now in
      clinical use. Our own antibody, C225 against the EGF receptor, shows great
      promise, but phase III trials need to be completed to prove its efficacy. The
      research efforts with C225 have involved scientists in academia, the
      pharmaceutical industry, and the National Cancer Institute, and contributions
      were made by many collaborators. I believe it is highly likely that blockade of
      growth factor-mediated signal transduction pathways, in combination with
      chemotherapy or radiotherapy, will enhance our ability to inhibit, and in some
      cases to eradicate, many of the common epithelial human malignancies (60).

PMID- 10881337
TI  - Molecular and pathophysiologic mechanisms of hyperkalemic metabolic acidosis.
AB  - In summary, hyperkalemia may have a dramatic impact on ammonium production and
      excretion. Chronic hyperkalemia decreases ammonium production in the proximal
      tubule and whole kidney, inhibits absorption of NH4+ in the mTALH, reduces
      medullary interstitial concentrations of NH4+ and NH3, and decreases entry of
      NH4+ and NH3 into the medullary collecting duct. The potential for development of
      a hyperchloremic metabolic acidosis is greatly augmented when renal insufficiency
      with associated reduction in functional renal mass coexists with the
      hyperkalemia, or in the presence of aldosterone deficiency or resistance. Such a
      cascade of events helps to explain, in part, the hyperchloremic metabolic
      acidosis and reduction in net acid excretion characteristic of several
      experimental models of hyperkalemic-hyperchloremic metabolic acidosis including:
      obstructive nephropathy, selective aldosterone deficiency, and chronic amiloride
      administration (7.9).

PMID- 10881338
TI  - Anti-cancer activity of 9-nitrocamptothecin liposome aerosol in mice.

PMID- 10881339
TI  - A transgenic mouse model of steatosis and hepatocellular carcinoma associated
      with chronic hepatitis C virus infection in humans.

PMID- 10881340
TI  - Nitric oxide insufficiency and arterial thrombosis.

PMID- 10881342
TI  - Remedial education: can this doctor be saved?
AB  - In the first two years of the program 30 physicians have completed the program. A
      list of the distribution of specialties/practice areas [table: see text] served
      is provided in Table 1. The data reveal that the distribution of practice areas
      corresponds approximately to the distribution of physicians practicing in the
      state. The UF C.A.R.E.S Program provides a great benefit to physicians and their
      patients. It provides an atmosphere of professional collaboration and
      encouragement to address specific educational needs and underscores a commitment
      to providing continuing medical education, meaningful doctor-to-doctor
      collaboration, better patient care, and reflects a medical model of diagnosis and
      treatment of specific problems.

PMID- 10881341
TI  - Osler's choice: one person's perspective on the past and future of internal
      medicine.

PMID- 10881344
TI  - Theodore Woodward Award. Pathogenesis of biochemical abnormalities in
      protoporphyria.
AB  - In summary, FC gene mutations in patients with protoporphyric liver disease
      typically cause major structural alterations in the FC protein. However, the gene
      mutations by themselves do not satisfactorily account for the severe phenotype,
      as the same mutations are found in asymptomatic family members, and similar
      mutations are found in patients who do not develop liver disease. Thus there may
      be unidentified factors in the FC gene locus, or factors outside the locus, which
      are also important in determining the degree of protoporphyrin accumulation that
      occurs in an individual patient, hence, the potential for developing significant
      liver disease. Further studies are needed to clarify this possibility and
      identify those factors.

PMID- 10881343
TI  - The Gordon Wilson Lecture. Natural history and treatment of early stage prostate
      cancer.
AB  - Prostate cancer poses a challenge to society and to physicians. It is a
      remarkably prevalent tumor, perhaps the most common cancer in the world in its
      histologic manifestation. In its clinically apparent form, it is notably
      heterogeneous. Some patients live out their lives with a prostate cancer that
      remains stable for decades without treatment. In other cases, the cancer grows
      aggressively, responds poorly to therapy, and causes death within a few years.
      The median loss-of-life expectancy for men diagnosed with prostate cancer has
      been estimated at 9 years. Important advances have been made in the past two
      decades in the treatment of prostate cancer. Further progress will require more
      accurate characterization of the primary tumor in each individual patient to
      tailor treatment--whether conservative or aggressive, surgery or radiation--more
      accurately to the nature of the individual cancer. Imaging studies in particular
      must be improved if we are to have better, noninvasive ways to identify the
      presence of a cancer and to define its volume, location, and extent. Substantial
      progress against this disease will require major breakthroughs in our
      understanding of the etiology of prostate cancer, the development of effective
      chemopreventive agents, more accurate ways to assess the biological potential of
      the tumor, and more effective systemic agents to treat metastatic cancer.

PMID- 10881345
TI  - Mechanisms accelerating muscle atrophy in catabolic diseases.
AB  - In summary, muscle protein loss in uremia is related to activation of the
      ubiquitin-proteasome proteolytic system to degrade muscle proteins. This response
      invariably includes increased transcription of genes encoding components of this
      pathway, suggesting that these illnesses stimulate a program of catabolism.
      Signals that could activate muscle protein degradation by this system in CRF
      include metabolic acidosis, impaired response to insulin and high circulating
      levels of cytokines. The activation mechanism also involves glucocorticoids which
      are necessary but not sufficient to activate protein degradation in muscle.

PMID- 10881347
TI  - Continuous professional development in internal medicine: recertification as a
      measure of professional accountability and quality improvement.

PMID- 10881348
TI  - GigaPoPs, teraflops and haptics: new medicines for the new millennium?

PMID- 10881349
TI  - [The results of trigeminal nucleotractotomy in facial pain].
AB  - In 1987 to 1997, open ultrasonic vertical trigeminal nucleotractotomy was
      performed in 46 patients with drug-resistant facial pain syndromes. There were 29
      patients with deafferentation pain, 14 with migraine-induced neuralgia and 3 with
      trigeminal neuralgia due to multiple sclerosis. The operation included unilateral
      suboccipital craniotomy, C1 hemilaminectomy and vertical destruction of the
      trigeminal nucleus and descending tract with an ultrasonic microsurgical needle.
      The rostral limit of trigeminal nucleotractotomy depended on the site of facial
      pain. In the early postoperative period, there were good (relief of baseline pain
      or mild pain requiring no medical therapy) in 44 (96%) patients and poor results
      in 2 (4%). Late results of follow-ups lasting 1 to 11 years (mean 6.1 years) were
      known in 39 patients. Good, fair (pain control with medication), and bad results
      were preserved in 25 (64%), 4 (10%), and 10 (26%) patients. Trigeminal
      nucleotractotomy is effective in relieving intractable facial pain.

PMID- 10881346
TI  - Myofibroblasts: paracrine cells important in health and disease.

PMID- 10881350
TI  - [The endoscopic diagnosis and differential treatment of the complications of
      shunting operations in children].
AB  - The authors present their experience with endoscopic diagnosis and differential
      treatment of children with complications after bypass surgery. They show the
      present-day potentialities, spectrum of surgical interventions and role of video
      assisted neuroendoscopic surgery in determining a treatment policy and choosing
      its method. A principle of multiportality was defined and substantiated, a
      diagnosis and treatment algorithm for children with this pathology was proposed
      by using the new minimum invasive technique video-assisted surgery.

PMID- 10881351
TI  - [The surgical treatment of traumatic dislocations of the cervical spine].
AB  - Thirty patients with injury-induced complete and incomplete dislocations and of
      the cervical vertebral column were operated on. New and old dislocations (up to
      28 days) were managed by the open reduction and stabilization of an injured
      segment by a two-vane monolithic corundum ceramic endoprosthesis. If there was a
      significant stability of the injured segment and if temporary external fixation
      could not be applied, C-shaped braces providing effects of thermomechanical shape
      memory were used. In old injury, corporectomy was performed by means of anterior
      wedging corporodesis with an autogenous bone graft or implants made from porous
      nickelled titanium.

PMID- 10881352
TI  - [The role of somatosensory evoked potentials in evaluating the treatment of
      patients with degenerative-dystrophic diseases of the lumbosacral spine].
AB  - Somatosensory evoked potentials (SSEP) were dynamically studied through bilateral
      stimulation of n. tibialis at the cortical and spinal level in 160 patients with
      degenerative and dystrophic lumbosacral diseases. The study revealed significant
      changes in the peaks Pf, N21 and in the intervals Pf-N21 in 38 (23.75%) patients.
      The patients had generally vascular disorders as ascending arterial, venous or
      concomitant myeloradicopathies (the syndromes of venous or arterial ischemia of
      the epiconus or conus). There were SSEP no significant changes in the paralyzing
      ischiasis syndrome. Early decompressing operations on the vertebral column
      (within 1 to 3 months) led to reversal of neurological disorders in most
      patients. Thus, SSEP in combination with needle and stimulant electromyography
      may quantitatively assess the time course of changes in the spinal cord
      conductors at and beneath the lumbar enlargement of the spinal cord in the
      treatment of degenerative and dystrophic lumbosacral diseases.

PMID- 10881353
TI  - [An epileptic syndrome in patients with the sequelae of gunshot craniocerebral
      wounds].
AB  - To study the specific features of the epileptic syndrome after present-day
      gunshot cranial wounds (GCW), as well as risk factors of its occurrence, 56
      victims were examined prospectively (within at least a year after their
      admission). The epileptic syndrome developed in 18 (32.1%) patients within 1 to
      15 months following GCW; there were prevalent generalized convulsive (in 13 of
      the 18 patients) and focal (in 12 of the 18 ones) seizures. One type of seizures
      was noted in 7 patients, two or three ones were in 11. The polymorphism of
      seizures and a disparity of their psychopathological structure to the side of
      brain lesion were typical for left-handers. As compared to other patients,
      epileptics were more commonly found to have: 1) frontoparietal lesion; 2)
      multiple bony defects of the vault of the skull; 3) enlargement of the lateral
      ventricle of the brain on CT scans; 4) primary coma for > 2 hours and other
      depressed consciousness syndromes for > 1 day; 5) signs of left-handedness. The
      findings suggest that there is a need for studies of the functional asymmetry of
      the brain to gain a better insight into the problem.

PMID- 10881354
TI  - [The successful treatment of a penetrating gunshot wound of the skull and brain
      in a child].

PMID- 10881355
TI  - [A fixation device for work with block preparations of the spine].

PMID- 10881356
TI  - [Pathophysiological aspects of traumatic injury to and regeneration of the spinal
      cord].

PMID- 10881357
TI  - [Jugular venous oximetry].

PMID- 10881358
TI  - South Africa on the eve of the XIIIth International AIDS Conference.

PMID- 10881359
TI  - Nutrition and HIV: Part 1, Wasting syndrome.

PMID- 10881360
TI  - Cooperation forms to accelerate access to AIDS care in developing countries.

PMID- 10881361
TI  - DuPont initiates Sustiva oral liquid expanded access program.

PMID- 10881362
TI  - UCSF launches international AIDS research program.

PMID- 10881363
TI  - New Web site for patients with chronic diseases.

PMID- 10881364
TI  - CEL-SCI offers South Africa a free license to use AIDS vaccine.

PMID- 10881365
TI  - Update: cancer risk in persons with HIV/AIDS in the era of combination
      antiretroviral therapy.
AB  - The incidence of AIDS-defining opportunistic infections has decreased markedly in
      persons with HIV who receive combination antiretroviral therapy, but less is
      known regarding the incidence of cancer. It does appear that the incidence of
      Kaposi sarcoma in persons receiving combination therapy has fallen dramatically.
      In contrast, reduction in the incidence of non-Hodgkin lymphoma (NHL) has been
      smaller. Based on few data, it appears that the incidence of primary CNS NHL is
      significantly decreasing, whereas the incidence of systemic NHL has changed
      little. Certain other cancers, comprising cervical cancer, Hodgkin disease, anal
      cancer, and conjunctival cancer, occur at increased rates in some populations
      with AIDS, but there are few data on incidence trends since the widespread use of
      combination therapy. In the future, cancers associated with long-term mild immune
      suppression and B-cell stimulation may occur at increased rates in long-term
      survivors of HIV infection.

PMID- 10881366
TI  - Opportunistic infections. Gastric infections in HIV/AIDS.
AB  - Gastric infections in individuals with HIV/AIDS are uncommon. The exact incidence
      is difficult to determine, since many are asymptomatic. Bacterial, viral, fungal,
      and protozoan infections have all been reported. However, the likelihood of
      certain infections is dependent on the degree of immunosuppression. This article
      will review the diagnosis, clinical manifestations, and treatment of gastric
      infections in HIV/AIDS.

PMID- 10881367
TI  - Antiretroviral therapy. Sequencing antiretrovirals.
AB  - Sequencing of antiretroviral agents is of interest because the majority of HIV
      infected individuals in clinical practice experience virologic rebound after 1 to
      2 years of therapy. Sequencing strategies are based on the observation that
      different mutational patterns arise after exposure to particular antiretroviral
      agents within the same class and on preliminary data suggesting that not all
      mutations impart the same degree of cross-resistance to other agents of the same
      class. The ultimate goal of sequencing is to maximize the number of effective
      antiretroviral combinations available. While convincing data on the efficacy of
      sequencing strategies from large, randomized clinical trials are lacking, early
      data suggest that some sequencing strategies may be of benefit.

PMID- 10881368
TI  - Reversal of cachexia in patients treated with potent antiretroviral therapy.
AB  - The introduction of HAART has changed the nutritional status of HIV patients. In
      the pre-protease inhibitor (PI) era, more than 60% of HIV-positive persons
      presented with protein energy malnutrition (PEM) and vitamin and mineral deficit.
      This caused progressive physical-metabolic wasting (wasting syndrome/cachexia)
      and increased susceptibility to opportunistic infections and drug toxicity. PEM
      was a concurrent cause in 80% of deaths attributed to AIDS. Since 1996, the year
      in which PIs were introduced, the number of patients dying as a result of AIDS
      has decreased by two thirds, and cachexia is no longer the AIDS terminal phase in
      developed countries. But different patterns of nutritional status changes have
      appeared in association with the use of newer anti-HIV therapies and with longer
      survival of HIV-infected patients. A new clinical and laboratory syndrome-
      lipodystrophy syndrome--now affects patients receiving PI-based therapy. This
      syndrome consists of changes in body shape that are caused by an abnormal
      redistribution of fat. Fat accumulates in the abdominal area (truncal and
      visceral obesity), in the axillary pads (bilateral symmetric lipomatosis), and in
      the dorsocervical pads ("buffalo hump," "bull neck") but decreases in the legs,
      arms, and nasolabial and cheek pads (peripheral lipodystrophy). Hyperlipidemia
      and insulin resistance are also frequently present (metabolic syndrome X).
      Pathogenic mechanisms of lipid and fat tissue disturbances are discussed in this
      article, and the clinical approach to patient management and therapeutic options
      for lipodystrophy and lipid dysmetabolism is evaluated.

PMID- 10881369
TI  - Incidental treatment of hepatitis B virus infection in an AIDS patient.

PMID- 10881370
TI  - Applications of expert systems in medicine.

PMID- 10881371
TI  - Hyponatremia in the intensive care: from diagnosis to treatment.

PMID- 10881372
TI  - Update on sepsis: pathophysiology and treatment.
AB  - Sepsis results from the activation of a complex cascade of mediators, an
      appropriate and necessary body response to infection or insult which can,
      however, become excessive and detrimental to the host. When the immunological
      host response is not well controlled, it may lead to multiple organ failure and
      death. This manuscript reviews the epidemiology and the major factors involved in
      the development of sepsis, and considers a number of therapeutic interventions
      that may help to better control the septic process and the related development of
      multiple organ failure.

PMID- 10881373
TI  - African iron overload.
AB  - African iron overload has been recognised in sub-Saharan Africa for seventy
      years. The condition is distinct from the well-characterised HLA-linked
      haemochromatosis described in Caucasians. Increased dietary iron intake
      predisposes to the condition. Recent evidence suggest that African iron overload
      may be caused by an interaction between increased dietary iron and a genetic
      defect not associated with the HLA-locus. Iron deposition is prominent both in
      macrophages and in hepatic parenchymal cells. Iron overload is distinct from
      alcoholic liver disease, although the excess dietary iron is derived from a
      traditional beverage that contains alcohol. African iron overload has clinical
      consequences. It is a cause of hepatic fibrosis and cirrhosis, and associations
      with diabetes mellitus, peritonitis, scurvy and osteoporosis have been described.
      African iron overload may be a cause of hepatocellular carcinoma. The disorder is
      associated with a poor outcome in tuberculosis, an infection that is highly
      prevalent in sub-Saharan Africa.

PMID- 10881374
TI  - Spontaneous internal jugular vein thrombosis: primary manifestation of a
      colorectal adenocarcinoma in a very old woman.
AB  - We report the history of a very old woman with a spontaneous internal jugular
      vein thrombosis as the presenting feature of an occult adenocarcinoma of the
      caecum. Spontaneous internal jugular vein thrombosis is an unusual form of venous
      thrombosis. Doppler ultrasound and Computed Tomography or Magnetic Resonance
      Imaging should confirm signs and symptoms suggesting thrombosis. Immediate
      anticoagulation with heparin followed by oral anticoagulation is mandatory to
      reduce associated mortality and morbidity. If no risk factors for internal
      jugular vein thrombosis are present, a work-up for hypercoagulable states and a
      careful search for distant malignancy should been obtained. If screening shows no
      obvious malignancy, further follow-up is necessary.

PMID- 10881375
TI  - Multicentric Castleman's disease in 2 patients with HIV infection, unresponsive
      to antiviral therapy.
AB  - Two HIV infected patients with multicentric Castleman's disease (MCD) and
      Kaposi's sarcoma are reported. Both died despite combination antiretroviral
      therapy including protease inhibitors.

PMID- 10881376
TI  - Breast cancer during pregnancy: cases and review of treatment and prognosis.

PMID- 10881377
TI  - [An unusual complication of bronchitis: Sweet's syndrome].
AB  - Sweet's syndrome (acute febrile neutophilic deromatosis) is a rare but not
      exceptional disease. Its first description was done in 1964, and its diagnosis is
      now well defined. A few days after a common upper respiratory infection, out
      patient presented erythematous plaques on the head, neck and forearms, with fever
      and general malaise. A skin biopsy showed a neutrophilic infiltrate. Oral
      steroids were prescribed, and healing occured within 48 hours. Respiratory and
      gastointestinal infections are frequently associated with Sweet's syndrom. Other
      associations have been described: neoplasias (mainly hemoproliferative diseases),
      inflammatory diseases, pregnancy, drugs. Cases classified as 'idiopathic' need a
      close follow-up: Sweet's syndrome may announce a malignant disease. There are
      also intermediate forms with other neutrophilic dermatoses, e.g. pyoderma
      gangrenosum.

PMID- 10881378
TI  - [The development of general internal medicine in the United States].

PMID- 10881379
TI  - Characteristics of women in jail and treatment orientations. A review.
AB  - Women who have been incarcerated are a high-risk group for criminal recidivism,
      and criminal justice statistics indicate that females are increasing in numbers
      more rapidly than the male detainee population. According to data from
      epidemiologic studies, incarcerated women are often young, single, mothers from
      ethnic minority backgrounds who have little education and poor work histories.
      Mental illness, drug abuse, and risky behaviors relating to contracting HIV/AIDS
      are common problems among female detainees. In this report, research into
      characteristics of women in jail and literature relating to treatment programs
      for incarcerated women are reviewed. Implications relating to treatment needs,
      program development, and further research are discussed. A case example and
      treatment intervention are presented based on this review.

PMID- 10881380
TI  - Sexual compatibility and the sexual desire-motivation relation in females with
      hypoactive sexual desire disorder.
AB  - Fifty-four female participants with hypoactive sexual desire disorder supplied
      daily reports of their sexual desire and motivation. The relation between desire
      and motivation remained statistically significant when controlling for sexual
      compatibility, sexual stress, sexual fantasy, and marital and sexual
      satisfaction. Findings suggest that (a) women higher in sexual compatibility
      experience greater sexual motivation regardless of their marital and sexual
      satisfaction, their sexual desire intensity, and depressive symptomatology; and
      (b) the relation between sexual compatibility and sexual desire is mediated by
      the propensity of those women high in sexual compatibility to have greater
      marital and sexual satisfaction. Within-subject analyses that controlled for
      autocorrelation and linear trends in the time series revealed that 40% of the
      women experienced significantly higher sexual motivation on greater sexual desire
      days. A discussion of these findings and evidence for the addition of sexual
      motivation as a distinct phase in the human sexual response cycle are explored.

PMID- 10881381
TI  - Cueing, demand fading, and positive reinforcement to establish self-feeding and
      oral consumption in a child with chronic food refusal.
AB  - A 3-year-old child with multiple medical disorders and chronic food refusal was
      treated successfully using a program that incorporated antecedent control
      procedures combined with positive reinforcement. The antecedent manipulations
      included visual cueing of a criterion number of self-feeding responses that were
      required during meals to receive reinforcement and a gradual increase in the
      imposed criterion (demand fading) that was based on improved frequency of oral
      consumption. As evaluated in a changing criterion design, the child learned to
      feed himself as an outcome of treatment. One year following intervention, he was
      consuming a variety of foods and had gained weight. Advantages of antecedent
      control methods for the treatment of chronic food refusal are discussed.

PMID- 10881382
TI  - Parametric analysis of overcorrection duration effects. Is longer really better
      than shorter?
AB  - Positive practice overcorrection (PPOC) has long played a significant role in the
      behavioral treatment of serious self-stimulatory behavior. Three experiments
      comparing the effectiveness of 30-second, 2-minute, and 8-minute PPOC on
      reduction of stereotypic hand behavior of adults with severe to profound
      developmental disabilities were conducted to resolve inconsistencies in
      previously reported findings concerning the role of PPOC duration in response
      suppression. Experiment 1, which used an alternating treatments--multiple
      baseline design, suggested that the different durations were equally effective in
      reducing the stereotypic behaviors to near-zero levels. Experiment 2, which used
      a reversal design, supported the findings of Experiment 1. Experiment 3, which
      used a reversal design to test the shortest and longest durations, generally
      confirmed the results of the first two experiments. This study therefore failed
      to support the oft-claimed superiority of long-duration PPOC. The possible
      factors underlying these findings and their implications for future research and
      practice are discussed.

PMID- 10881383
TI  - Research on posttreatment return of claustrophobic fear, arousal, and avoidance
      using mock diagnostic imaging.
AB  - Fear sometimes returns after attenuation via exposure. Return of fear is poorly
      understood due to conflicting results from diverse experiments. This article
      reports on two experiments in which claustrophobic fear during mock diagnostic
      imaging was attenuated and allowed to return so the experiments could be
      evaluated and return of fear studied. Attentional focus versus distraction during
      exposure was a between-subjects independent variable. Attempts were made to
      predict return of fear, return of heart-rate responsivity, and behavioral
      avoidance using levels of fear and heart-rate during initial mock diagnostic
      imaging as predictor variables. One third of participants displayed return of
      fear, heart-rate response, or avoidance 1 week after fear reduction. Heart-rate
      response during initial mock imaging predicted posttreatment return-of-fear
      classification; level of fear during initial imaging did not. Neither initial
      heart rate nor initial fear predicted return of heart-rate reactivity or
      avoidance. The experiments are offered as models for programmatic research.

PMID- 10881384
TI  - Shaping oral feeding in a gastronomy tube-dependent child in natural settings.
AB  - A 3-year-old medically fragile girl who refused to eat after prolonged and
      frequent hospitalizations was started on a feeding program in the home and school
      settings. She exhibited food aversions and received all nourishment via a
      gastronomy tube. Preevaluation observations of her feeding behavior revealed that
      she refused all presented drinks and foods. Treatment was two-fold. First, food
      acceptance was followed by social praise and access to preferred toy play, and
      second, food refusal and disruptive behaviors were ignored. Gagging, vomiting,
      and crying occurred periodically during initial feedings. In addition, there were
      medical complications during the course of treatment necessitating continuous
      modifications of the program. Results of a multiple-phase design showed marked
      increases in the amount of food consumed at home, which then generalized to the
      school setting.

PMID- 10881385
TI  - Revealed preference between reinforcers used to examine hypotheses about
      behavioral consistencies.
AB  - New techniques for measuring preference between reinforcers have emerged in a
      field known as behavioral economics. Preference is assessed from the relative
      shapes of reinforcer demand functions, shown in graphs in which rate of
      reinforcement is plotted against schedule requirement. In economic terminology, a
      schedule requirement sets the price of a reinforcer as it sets the numbers of
      responses needed to obtain a reinforcer. Relative shapes of demand functions for
      alternative reinforcers are interpreted using the principle of revealed
      preference, as the shape of a demand function reflects the numbers of responses
      emitted to obtain reinforcers at each schedule requirement. Individual
      preferences between reinforcers are measured from differences in shapes of demand
      functions. Demand functions from two single subject experiments are examined to
      assess the hypothesis that individuals may generate differently shaped demand
      functions for the same reinforcers. It is hypothesized that individual
      differences in reinforcer preference may be related to consistent differences in
      behavior such as those observed in personality traits.

PMID- 10881386
TI  - White bears and other elusive intrusions. Assessing the relevance of thought
      suppression for obsessional phenomena.
AB  - According to recent research, deliberate suppression of unwanted thoughts may
      result in a paradoxical increase in their frequency. Recent cognitive-behavioral
      theories of obsessive-compulsive disorder now consider active thought suppression
      to be a crucial factor in the pathogenesis of obsessions. However, there are
      considerable inconsistencies in the results of studies investigating the thought
      suppression paradox that make it difficult to apply findings to obsessional
      problems. Furthermore, many studies have low ecological validity for obsessional
      problems. This article reviews the thought suppression research, discusses
      methodological issues relevant to application of the thought suppression paradox
      to obsessional problems, and offers recommendations for future research.

PMID- 10881387
TI  - The behavioural ecology of mixed-species troops of callitrichine primates.
AB  - This review summarizes information on the behavioural ecology of mixed-species
      troops (interspecific associations) formed by different species of
      callitrichines, small New World monkeys, in western and central Amazonia. The
      formation of mixed-species troops is an integral part of the biology of several
      species of this subfamily. Niche separation between associated species is
      obtained through vertical segregation which results in differences in the prey
      spectrum. The degree of niche separation is a predictor for the stability of
      mixed-species troops. Individuals may benefit from the formation of mixed-species
      troops through increased safety from predators, increased foraging efficiency,
      and/or increased resource defence. Costs of mixed-species troop formation are
      probably very low and mainly relate to patterns of interspecific behavioural
      interactions. We point to gaps in our knowledge and suggest pathways for future
      research into mixed-species troops.

PMID- 10881388
TI  - Conodont affinity and chordate phylogeny.
AB  - Current information on the conodonts Clydagnathus windsorensis (Globensky) and
      Promissum pulchrum Kovacs-Endrody, together with the latest interpretations of
      conodont hard tissues, are reviewed and it is concluded that sufficient evidence
      exists to justify interpretation of the conodonts on a chordate model. A new
      phylogenetic analysis is undertaken, consisting of 17 chordate taxa and 103
      morphological, physiological and biochemical characters; conodonts are included
      as a primary taxon. Various experiments with character coding, taxon deletion and
      the use of constraint trees are carried out. We conclude that conodonts are
      cladistically more derived than either hagfishes or lampreys because they possess
      a mineralised dermal skeleton and that they are the most plesiomorphic member of
      the total group Gnathostomata. We discuss the evolution of the nervous and
      sensory systems and the skeleton in the context of our optimal phylogenetic tree.
      There appears to be no simple evolution of free to canal-enclosed neuromasts;
      organised neuromasts within canals appear to have arisen at least three times
      from free neuromasts or neuromasts arranged within grooves. The mineralised
      vertebrate skeleton first appeared as odontodes of dentine or dentine plus enamel
      in the paraconodont/euconodont feeding apparatus. Bone appeared later, co
      ordinate with the development of a dermal skeleton, and it appears to have been
      primitively acellular. Atubular dentine is more primitive than tubular dentine.
      However, the subsequent distribution of the different types of dentine (e.g.
      mesodentine, orthodentine), suggests that these tissue types are homoplastic. The
      topology of relationships and known stratigraphic ranges of taxa in our phylogeny
      predict the existence of myxinoids and petromyzontids in the Cambrian.

PMID- 10881389
TI  - A critical reappraisal of the fossil record of the bilaterian phyla.
AB  - It has long been assumed that the extant bilaterian phyla generally have their
      origin in the Cambrian explosion, when they appear in an essentially modern form.
      Both these assumptions are questionable. A strict application of stem- and crown
      group concepts to phyla shows that although the branching points of many clades
      may have occurred in the Early Cambrian or before, the appearance of the modern
      body plans was in most cases later: very few bilaterian phyla sensu stricto have
      demonstrable representatives in the earliest Cambrian. Given that the early
      branching points of major clades is an inevitable result of the geometry of clade
      diversification, the alleged phenomenon of phyla appearing early and remaining
      morphologically static is seen not to require particular explanation. Confusion
      in the definition of a phylum has thus led to attempts to explain (especially
      from a developmental perspective) a feature that is partly inevitable, partly
      illusory. We critically discuss models for Proterozoic diversification based on
      small body size, limited developmental capacity and poor preservation and cryptic
      habits, and show that the prospect of lineage diversification occurring early in
      the Proterozoic can be seen to be unlikely on grounds of both parsimony and
      functional morphology. Indeed, the combination of the body and trace fossil
      record demonstrates a progressive diversification through the end of the
      Proterozoic well into the Cambrian and beyond, a picture consistent with body
      plans being assembled during this time. Body-plan characters are likely to have
      been acquired monophyletically in the history of the bilaterians, and a model
      explaining the diversity in just one of them, the coelom, is presented. This
      analysis points to the requirement for a careful application of systematic
      methodology before explanations are sought for alleged patterns of constraint and
      flexibility.

PMID- 10881390
TI  - Research on the development of academic skills: introduction to the special issue
      on early literacy and early numeracy.

PMID- 10881391
TI  - Home literacy activities and their influence on early literacy skills.
AB  - The relationship between the home environments of 66 children and their language
      and literacy development was examined. After accounting for child age, parent
      education, and child ability as indexed by scores on a rapid automatized naming
      task and Block Design of the WPPSI-R, shared book reading at home made no
      contribution to the prediction of the literacy skills of letter name and letter
      sound knowledge in kindergarten. In contrast, home activities involving letters
      predicted modest and statistically significant amounts of variance. For the areas
      of receptive vocabulary and phonological sensitivity, neither shared book reading
      nor letter activities were predictive. Follow-up to mid-Grade 2 underscored the
      importance of letter name/sound knowledge and phonological sensitivity in
      kindergarten in accounting for individual differences in later achievement in
      reading comprehension, phonological spelling, and conventional spelling.

PMID- 10881392
TI  - Morphological effects in children's spelling of French words.
AB  - The present study examined whether primary school children represent
      morphological information when spelling French words that have silent-consonant
      endings (e.g., chat). Children in grades 2 (n = 57) and 4 (n = 55) spelled
      regular, morphological, and deep words. The morphological and deep words differed
      in the presence or absence of derivatives that revealed the nature of the silent
      consonant ending. As expected, regular words were the easiest to spell whereas
      morphological words (for which the silent consonant could be derived) were easier
      to spell than were deep words (for which the silent consonant must be memorized).
      Children's linguistic knowledge of morphology made a contribution to their
      spelling of morphological words that was independent of reading experience,
      vocabulary, spelling ability (i.e., spelling regular words), and phoneme
      awareness.

PMID- 10881393
TI  - On subtypes of developmental dyslexia: evidence from processing time and accuracy
      scores.
AB  - Phonological dyslexics (Ph-DYS) are characterized by a phonological deficit,
      while surface dyslexics (S-DYS) are characterized by an orthographic deficit.
      Four issues were addressed in this study. First, we determined the proportion of
      Ph-DYS and S-DYS in a population of French dyslexics by applying Castles and
      Coltheart's (1993) regression method to two previously unused diagnostic
      measures: pseudo-word and irregular-word processing time. Thirty-one dyslexics
      were matched to 19 average readers of the same age (10 years, CA controls) and to
      19 younger children of the same reading level (8 years, RL controls). Compared to
      CA controls, there were more Ph-DYS than S-DYS. Compared to RL controls, there
      were still a high number of Ph-DYS; however, the S-DYS profile almost
      disappeared. Next, we examined the reliability of these subtypes across different
      measures of phonological and orthographic skills. Compared to RL controls, both
      groups of dyslexics were found to be impaired only in phonological skills, either
      in processing time (Ph-DYS) or in accuracy (S-DYS). Then we assessed the moment
      at which the two dissociated profiles emerged in the course of cognitive
      development. In order to do so, we examined earlier longitudinal data, collected
      when the children were 7 and 8 years old, and found that only the S-DYS's
      orthographic deficit increased with development. Last, we looked at whether the
      Ph-DYS and S-DYS profiles were associated with other specific cognitive deficits.
      Specific deficits in phonemic awareness and in phonological short-term memory
      were found for both Ph-DYS and S-DYS. These data suggest that developmental
      dyslexia could be largely accounted for by an underlying phonological impairment.

PMID- 10881394
TI  - Preschoolers doing arithmetic: the concepts are willing but the working memory is
      weak.
AB  - The study of early mathematical development provides important insights into
      young children's emerging academic competencies and, potentially, a basis for
      adapting instructional methods. We presented nonverbal forms of two- and three
      term arithmetic problems to 4-year-olds to determine (a) the extent to which
      certain information-processing demands make some problems more difficult than
      others and (b) whether preschoolers use arithmetic concepts spontaneously when
      solving novel problems. Children's accuracy on simple arithmetic problems (a + b
      and a - b) was strongly related (r2 = .88) to representational set size, the
      maximum number of units that need to be held in working memory to solve a given
      problem. Some children also showed spontaneous use of procedures based on the
      arithmetic principle of inversion when solving problems of the form a + b - b.
      These results highlight the importance of identifying information-processing and
      conceptual characteristics in the early development of mathematical cognition.

PMID- 10881395
TI  - Representing quantity beyond whole numbers: some, none, and part.
AB  - Previous research has demonstrated how children develop the ability to use
      notational representations to indicate simple quantities. These studies have
      shown a developmental shift from the use of idiosyncratic, to analogical, to
      conventional, numerical notations. The present paper extends these findings by
      reporting the results from a study in which children from 3 to 7 years old were
      asked to write a representation to indicate a quantity presented in a game-like
      scenario. Three kinds of quantities were included: whole numbers, zeros, and
      fractions. The children's notations were shown to them shortly after they were
      produced and then again two weeks later to see if children could interpret them.
      The results showed the familiar developmental pattern towards increased use of
      conventional notations for all quantities. The ability to read the notations was
      greatest for conventional numbers where performance was at ceiling, lower for
      analogue representations, and very poor for idiosyncratic global recordings.
      Children's choice of a notational format was influenced almost entirely by their
      age and not by the quantity being represented. Children were able to solve the
      zero problems almost as well as they could the whole numbers, but their
      understanding and use of representations for fractions was very limited.

PMID- 10881396
TI  - Ordinal knowledge: number names and number concepts in Chinese and English.
AB  - Previous research has demonstrated cross-language variation in early counting
      associated with linguistic differences in number-naming systems. Ordinal number
      names are typically learned later than cardinal names, but languages also differ
      in the regularity with which they form these names. Elementary school children in
      China and the U.S. showed differences in the acquisition and use of ordinal
      numbers corresponding to linguistic differences in ordinal names in their native
      languages. On tasks assessing children's conceptual knowledge of ordinal
      relations, a more complicated picture emerged. These results suggest that (a)
      children induce their language's set of ordinal number names by generalization
      based on rules sanctioned by early examples, and (b) the relation between ordinal
      names and ordinal concepts is a complex one, with language only one source of
      difficulty in understanding ordinal relations. Implications for studies of the
      relation between linguistic structure and cognitive development are discussed, in
      particular the possibility that effects of linguistic differences may vary for
      different levels of development and for different aspects of cognition.

PMID- 10881397
TI  - Children's strategy use in computational estimation.
AB  - This study reports an investigation of ten-year-old children's strategy use in
      computational estimation (i.e., give an approximate answer like 400 to an
      arithmetic problem like 224 + 213). Children used four strategies: rounding with
      decomposition, rounding without decomposition, truncation, and compensation.
      Strategies appeared to differ in frequency and effectiveness. Finally, children
      chose strategies in an adaptive way so as to obtain fast and accurate
      performance. Implications of these findings for understanding children's
      computational estimation performance and strategies in numerical cognition in
      general are discussed.

PMID- 10881398
TI  - Serious unexplained illness among drug injectors.

PMID- 10881399
TI  - National sentinel surveillance of antimicrobial resistance in Neisseria
      gonorrhoeae.

PMID- 10881400
TI  - [Problems of ambient air hygiene and ways of their solution in the near future].

PMID- 10881401
TI  - [Prospective trends of hygienic studies of the urbanized dwelling environment].

PMID- 10881402
TI  - [Hygienic aspects of ultraviolet irradiation disinfection of sewage].

PMID- 10881403
TI  - [Impact of short-term increase in air pollution on mortality of the population].
AB  - The authors analyzed whether there is an association of mortality with ambient
      air pollution analyzed in Yekaterinburg and Nizhni Tagil in 1994 to 1997. There
      was a positive correlation between general mortality and CO or SO2
      concentrations, between cardiovascular mortality and dust, NH3 or phenol, between
      mortality and CO or NH3. An increase of deaths as percents per 10 micrograms/m3
      dust was calculated.

PMID- 10881404
TI  - [Hygienic significance of geohydrochemical features of the Moscow region].
AB  - The biochemical features of the Moscow artesian pool and the influence of water
      on the population's health are shown. The paper present information on the
      sources of the water-supply system in the town of Zelenograd whose population
      uses river and artesian waters. The drinking water in Zelenograd and in the
      populated areas of the Moscow Region contains toxic elements, such lithium, born,
      strontium, fluorine, barium in the quantities greater than the adopted
      specifications. It is stated that the presents of the above agents in the waters
      of the Moscow artesian pool suggests regional geochemical anomaly. Mixing
      artesian and river waters in Zelenograd has a positive effect, by causing a
      reduction in the incidence of fluorosis.

PMID- 10881405
TI  - [Effects of combined radioactive and pesticide loads on the population health].
AB  - Relationships of the magnitude of environmental radioactive and pesticide factors
      to morbidity were studied. Comparative investigations showed that there was a
      correlation between the above environmental factors. Hygienic preventive measure
      for health promotion in ecologically poor areas (exposed to radiation or
      pesticides) were developed.

PMID- 10881406
TI  - [Prognosis of the hazards of chemical substances depending on structure-activity
      relationship in terms of biotransformation].

PMID- 10881407
TI  - [Hygienic assessment of primary metallurgic processing of natural alloy ores].
AB  - The working conditions for primary metallurgic processing of naturally alloyed
      ores differ from those for processing magnetic iron ores in high moisture, high
      concentrations of CO, SO2, aerosols of Si and Cr oxides. All these factors cause
      high incidence rates of chronic pulmonary and cardiovascular diseases in the
      workers. Naturally alloyed ores produce a greater pulmonary fibrogenic action
      than do magnetic iron ones.

PMID- 10881408
TI  - [Identification of high-risk groups at the examination of workers engaged in oil
      refining industry].
AB  - The health status of workers engaged in oil-refining industry was studied. The
      workers contacting with chemicals were found to have changes in the red blood
      cell adenyl system, blood and urine chemiluminescence, and monooxygenase system.

PMID- 10881409
TI  - [Tasks of hygiene of children and adolescents in the light of the Federal law "On
      the sanitary-epidemiologic wellbeing of the population" (1999)].

PMID- 10881410
TI  - [Health problems of school education reform].
AB  - The paper deals with impact of educational load in pupils at present general
      educational establishments on their health. The great total educational load in
      them was found to violate the schoolchildren's routine. This more frequently
      forms inadequate physiological responses, develops neurotic disorders. The
      incidence of chronic diseases is higher in children going to new-type schools.
      The findings provide evidence for some medical and organizational measures to
      promote schoolchildren's health.

PMID- 10881411
TI  - [Professional orientation of youth: medical and psychophysiological aspects].
AB  - The scientific and practical aspects of medical and psychophysiological
      professional orientation in teenagers and young people have become more and more
      pressing due to their poorer health along with higher demands for their
      resistance to unfavourable factors. The aid of a physician and a
      psychophysiologist in their choice of a future profession promotes the prevention
      of general and occupational morbidity. Work on professional orientation should be
      began at school in the 5th-6th and done through school life during which they get
      a general and vocational education. Guidelines have been developed for effective
      medical and physiological professional counselling.

PMID- 10881412
TI  - [Biologic cybernetics and ways of using it in the hygiene of children and
      adolescents].

PMID- 10881413
TI  - [Systemic approach to medical professional counseling to adolescents and young
      people].
AB  - An increasing importance of medical professional orientation of and medical
      specialist advice to teenagers and young people is evidenced. Data on morbidity
      among schoolchildren and young employed people are presented. The author shows it
      necessary to make new lists of medical contraindications for vocational training,
      a standard and methodological basis, and automatic systems for medical and
      professional orientation.

PMID- 10881414
TI  - [Present-day trends in adolescents' health].
AB  - The trends in teenagers' health in the past decade have been studied. A total of
      2442 pupils from general and vocational training schools have been examined.
      There have been increases in morbidity and in the incidence of social diseases,
      there has been a decrease in their physical development. Methodological
      approaches to examining the health status in this age group are presented.
      Examining the procedures developed for monitoring adolescents' health has shown
      that they yield positive results.

PMID- 10881415
TI  - [Health of children attending new-type schools].

PMID- 10881416
TI  - [Physical development of Moscow's schoolchildren during the past decade].
AB  - Long- and short-term follow-ups of the Moscow schoolchildren of the 1960s to the
      1990s show that acceleration of their growth and development has mainly ceased
      now. Certain changes have been found in the children's morphological status. The
      age of menarche has become 0.5 year older. The authors consider it necessary to
      perform follow-ups of physical development in a pediatric population along with
      sociohygienic monitoring.

PMID- 10881418
TI  - [Problems of prevention of mental disorders in school children].
AB  - The paper covers various aspects of schoolchildren's mental adaptation. The study
      has indicated that mental health is worse in 6th-9th-form pupils than that in
      junior schoolchildren. There is a relationship of the deviant behavior of
      schoolchildren and their mental health. The data of an anonymous questionnaire
      survey are given, which suggest that there is an increase in negative trends
      towards psychoactive drug abuse. Evidence shows it necessary to apply a
      comprehensive approach to solving the problems of schoolchildren health care.

PMID- 10881419
TI  - [Comprehensive evaluation of the physical development of school boys in an
      industrial town].

PMID- 10881417
TI  - [Growth and body mass of Russia's children based on cross-sectional studies of
      1994-1995].
AB  - The paper analyzes anthropometric data (height and body weight) in children and
      teenagers in 1994 to 1996. Height-weight ratios were derived as tables. The
      unique materials obtained and the authors' experience in this area may be useful
      in developing the anthropometric standards of Russia's children and adolescents.

PMID- 10881420
TI  - [Methodical aspects of toxicological-hygienic assessment of digestive function in
      experimental animals].

PMID- 10881421
TI  - [Evolutionary bioenergetic trap and progressive evolution of animals].
AB  - We propose a macroscopic pathway to increase energy metabolism during progressive
      evolution with reducing size of animal body. If standard metabolism significantly
      increases in the course of body size reduction through increased coefficient b
      from the allometric equation (1), two cases are possible: coefficient b remains
      constant (1) or returns to the normal value (2) at increasing body weight in a
      given animal group. In the first case, an animal group appears in an evolutionary
      trap considering possible increase in body size, since the standard metabolism at
      increasing weight becomes lower starting from a certain point as compared to
      other animals of the same type. In the second case, increasing body size elevates
      standard metabolism relative to other animals of the same type, which offers an
      evolutionary advantage to this group.

PMID- 10881423
TI  - [Cytopathology of plants infected with viruses. Ultrastructure of leguminous
      leaves infected with red clover mottle virus].
AB  - We studied ultrathin sections of clover, pea, and cowpea leaves from intact
      plants and after infection by red clover mottle virus (RCMV, comovirus, 28 nm
      isometric virions) under an electron microscope. Significant pathological changes
      were observed in the leaf cells after the infection: RCMV virions accumulated in
      the cytoplasm and vacuoles, tubular structures containing the virion-like
      particles, as well as vesicular aggregates were observed. Large membrane
      containing inclusions with long tubules (approximately 35 nm in diameter) were
      found in the cytoplasm of the infected clover chlorenchyma cells. Apparently,
      these novel inclusions correspond to virus-induced protein synthesis.

PMID- 10881422
TI  - [Phenylephrine synchromizes rhythm of protein synthesis in hepatocyte culture].
AB  - Published data indicate that 1-3 microM adrenomimetic phenylephrine increases the
      concentration of calcium ions in the cytoplasm of cultured hepatocytes. We
      studied low-density cultures exhibiting no protein synthesis rhythm in the fresh
      medium and demonstrated that a 2 min action of 2 microM phenylephrine induces
      protein synthesis rhythm, i.e., synchronizes the synthesis oscillations in
      hepatocytes. A similar effect was observed for a selective inhibitor of the
      reticulum calcium pump, di-tert-butyl-benzohydroquinone, that increases the
      cytoplasm concentration of calcium ions by a receptor-independent mechanism. A
      calcium antagonist imipramine obviated the synchronization effect of
      phenylephrine. We propose that short-term changes in the cytoplasm concentration
      of calcium ions covering the whole cell population are among intracellular
      mechanisms of protein synthesis synchronization in hepatocytes in vitro.

PMID- 10881424
TI  - [Use of S100b protein for optimization of cornea regeneration after surgery].
AB  - The results presented suggest a modulating effect of protein S100b on the course
      of inflammation in the cornea. In the presence of this protein, secretion of
      proteoglycans and collagen increases, their interrelationship is restored and
      tissue specificity of extracellular matrix is ensured, which allows preservation
      of the cornea transparency. Protein S100b appears to be a promising drug for
      ophthalmology, especially after refractional surgery on the cornea.

PMID- 10881425
TI  - [The role of cytochrome p450 in metabolism of S-ethynylthiophosphates].
AB  - We studied interaction between S-ethynyl ethers of phosphorus acids with
      cytochrome P-450 from rat liver and housefly abdomen. High thionic effect, i.e.,
      considerable selectivity for the studied compounds in homoiotherms and
      arthropods, proved to the related to the triple bond in these compounds.
      Apparently, cytochrome P-450 participates in S-ethynylthiophosphates metabolism
      and breaks the P-S bond. This gives rise to "self-destroying" metabolites,
      namely, alkylthioketenes, which decelerate deactivation reactions through
      destruction of the corresponding isoform of cytochrome P-450 in the microsomal
      fraction in both homoiotherms and insects. However, the activation reaction goes
      much faster in insects than in homoiotherms.

PMID- 10881426
TI  - [Evolutionary changes in amino acid composition of dicotyledonous seeds].
AB  - Amino acid composition of dicotyledonous seeds of 82 genera, 67 families, 48
      orders, and 8 subclasses (after Takhtadzhyan, 1987). Within the frames of
      hypothesis of amino acid composition of the least specialized hypothetical taxon
      we have established a universal trend for all dicotyledonous classes--increased
      proportion of glutamic acid and arginine. Divergent processes are pronounced in
      the evolution of amino acid composition within the families and orders. Pairwise
      comparison of amino acid composition in all analyzed taxons demonstrated high
      similarity between taxons from different subclasses and at different levels of
      biochemical specialization. Within the frames of the system proposed by
      Takhtadzhyan (1987) we interpret this as a clearly pronounced parallel
      variability of the seed amino acid composition realized during evolution of
      taxons in various dicotyledonous orders and subclasses.

PMID- 10881427
TI  - [A source of high frequency variations in the tracheid size in annual tree rings
      of conifers].
AB  - Statistical analysis of high-frequency variations in the radial dimensions of
      tracheids was carried out using precise measurements of five radial rows in each
      annual tree ring for several coniferous species: Larix gmelinii, L. leptolepis,
      L. sibirica, Picea abies, Pinus sylvestris, P. rigida, and P. densiflora. More
      than 25 tree rings with a varying number of cells and width were measured for
      each species. High-frequency variations in radial dimensions were found to have a
      regular (cyclic) characteristic and accumulated 5 to 11% of the total
      variability. The cyclic pattern was identified using Fourier analysis of time
      related or successive series statistical procedure. The first order
      autocorrelations (-0.45 to -0.74) and the mean cycle of high-frequency variations
      (2.1-2.5) did not depend on the number of cells in the annual ring, i.e., they
      are determined by internal causes. The cyclic pattern of high-frequency variation
      in tracheid dimensions is used to interpret the seasonal mechanism of xylem
      formation. Specifically, (1) high-frequency variations in the tracheid radial
      size take place during the last asymmetrical division of the xylem mother cell
      before transition to the elongation zone, (2) the final tracheid radial size is
      mostly determined within the zone of division due to the last asymmetrical
      division, and (3) acceleration of cell cycle from the initial to the periphery of
      the cambial zone. The results obtained are also discussed with respect to the
      mechanisms of xylem differentiation.

PMID- 10881428
TI  - [Various luminescence characteristics of allocytoplasmic wheat hybrids].
AB  - Comparative studies of thermoluminescence and slow fluorescence induction were
      carried out on leaves of allocytoplasmic hybrids and standard regionalized wheat
      (cultivar Zarya). There are differences in luminescence indices between these
      objects correlated to the thermoluminescence and slow fluorescence induction
      methods. These differences allow estimation of the functional activity of the
      photosynthetic system. All studied allocytoplasmic hybrids exceeded the standard
      wheat in both luminescence indices FM/FT (slow fluorescence induction) and
      SA/Stot (thermoluminescence) and productivity (height of seedlings, number of
      ears and grains, grain mass, etc.). The highest values of FM/FT and SA/Stot and
      the lowest value of SC/Stot were recorded in the allocytoplasmic hybrid Igen 3 x
      Mironovskaya 808, which is characterized by the highest productivity.

PMID- 10881429
TI  - [Circahoralian rhythms and integrative function of neurons].
AB  - The neuron's integrative function is directly related to circumhoralian rhythms
      of energy and plastic processes in the neuron's soma. The neuron's excitability
      and its integral reaction to a test stimulus are determined by the energy
      dependent accumulation of calcium ions and decreased aggregation of tigroid and
      mitochondria, as well as by changes in the soma and axon hill geometry. Upon
      synchronization of functional load and energy of the cell, an increased
      excitability of the neuron and formation of a temporal relationship are possible.

PMID- 10881430
TI  - [Effect of population density on ecological characteristics of the grass moth
      Loxostege sticticalis L. (Lepidoptera: Pyralidae) in the gradation cycle].
AB  - We continued to study the diversity of responses of the grass moth Loxostege
      sticticalis L. to variations of density. We estimated the dynamics of the
      internal state of individuals and considered the influence of the population
      prehistory on ecological characteristics of the phytophage. In experiments on
      studying the structure of flower forms of the larval stage, we showed the
      dependence of the parameters of the internal state of individuals on prehistory,
      specifically on the conditions of life and type of individuals of the preceding
      generation. At the same time, comparison of the experimental results of 1991 and
      1994 revealed a drift of the parameters of the reaction to variations in the
      grass moth population density by the structure of the larval flower forms and
      actual fertility of the imago. On the whole, the data obtained suggests that the
      studied species is characterized by a complex system of endogenous mechanisms
      underlying the regulation of numbers. The dynamics of environmental parameters is
      mediated by a cascade of endogenous rearrangements, as a result of which
      transition from depression to mass reproduction is realized through succession of
      the types of individuals in the population, when instead of a single phase, the
      flock phase starts to dominate.

PMID- 10881431
TI  - [Weight distribution and optical characteristics of soil humic acids fractionated
      by gel chromatography and electrophoresis].
AB  - Combination of gel chromatography on Sephadex and polyacrylamide gel
      electrophoresis was used to obtain molecular weight- and electrophoretic mobility
      uniform fractions of humic acids from soil of different types (chernozem, sod
      podzol, grey forest, and red soils). Extinction and color (E4/E6) coefficients,
      as well as weight distribution (%) were studied for all humic acids and their
      fractions. The fractions differed by the weight distribution (%). Sod-podzol and
      red soils had twice the amount of high-molecular and half the amount of low
      molecular HA fractions as compared to chernozem and grey forest soil.

PMID- 10881432
TI  - [Use of electron microscopy for study of animal brain synaptosomes].
AB  - Studies were carried out on the fraction of animal brain synaptosomes obtained by
      the method of differential centrifugation. We studied the possibility of using
      electron microscopy of ultrathin section and freeze-etching for assessment of the
      state of synaptosomal membranes and functional state of synaptosomes. The method
      of freeze-etching proved to be the most informative. In order to assess the state
      of synaptosomes, the following characteristics were used: coefficient of lateral
      diffusion and asymmetric distribution of intramembrane particles. It was also
      possible to identify mitochondria in the synaptosomal fraction using freeze
      etching, which is an important criterion of purity of the suspension of
      synaptosomes.

PMID- 10881433
TI  - [Biotope distribution of two gerbil species (Meriones meridianus and M.
      tamariscinus) (Rodentia, Gerbillinae) in southern Kalmykia].
AB  - Our studies have been conducted in Southern Kalmykia (Black Lands) in 1994-1996.
      The data obtained on the same territories in 1981-1983, as well as in 1997-1998
      were used for comparison. Over the studied period, the size of Meriones
      tamariscinus population underwent a significant increase. In the early 1980s, the
      colonies of this species were found only on sandy dunes covered with tamarix. At
      the present time, M. tamariscinus populations have spread over stabilized sands,
      abandoned shepherd camps, and riparian thickets of tamarix along the shores of
      lakes. Both gerbils species (M. meridianus and M. tamariscinus) establish joint
      colonies in all biotopes, but not in riparian tamarix thickets near lakes, where
      only Meriones tamariscinus have been found. The abundance of food and favorable
      conditions for burrowing in stable sands belong to factors, responsible for
      permanently high numbers of gerbils in these areas.

PMID- 10881434
TI  - [Comparative analysis of spectral-prosodic characteristics of the human prototype
      signals and phonation of the common maynah (Acridotheres tristis)].
AB  - A comparative study was carried out of the spectral-prosodic characteristics of
      phoneme "a" (vowel "ya" from Russian word "Byaka") pronounced by the common
      maynah and humans (a total of about 50 signals). A phenomenon of mutual express
      imitation has been established in the course of dialogue contact between the
      maynah and female speaker. Common similarity and difference features of the
      acoustic characteristics of the human and bird's signals have been revealed, as
      well individual similarity features of the signals upon the dialogue contact.

PMID- 10881435
TI  - [Diurnal cycles of endogenous phytohormones in barley].
AB  - We have studied diurnal courses of the free forms of phytohormones (abscisic
      acid, gibberellins, cytokinins, indolylacetic acid, and ethylene) in leaves of
      the spring variety of barley (Hordeum vulgare L.), cultivars Zazerskii 85 and
      Moskovskii 2 in vegetation experiments. The phytohormones were analyzed by gas
      liquid chromatography, immunoenzyme assays, and bioassays, using unfractionated
      plant material. Assays were conducted over a period of 22-24 h, every 2 h, during
      the phases of formation of the third leaf and tillering; for indolylacetic acid,
      assays were also conducted during the phases of booting and the beginning of
      flowering. It has been demonstrated that the ratio of phytohormones in the plant
      shows continuing changes over 24 h, and the rate of change of this ratio is
      extremely high. There is a certain functional relationship between changes in the
      hormonal balance and the accompanying growth processes. The proportion between
      phytohormones is also significantly affected by such environmental factors as
      temperature, air humidity, and lighting.

PMID- 10881436
TI  - Medicine and the Internet in the new millennium.

PMID- 10881437
TI  - [Breast cancer: prognostic value of flow cytometry and hormone receptors. Apropos
      of a Lebanese series of patients].
AB  - OBJECTIVES: This study has three objectives. 1) First to establish the influence
      of flow cytometry and hormone receptors on overall survival and disease free
      survival of stage I to IIIA breast cancer patients. 2) Second to search for
      associations between the classical prognostic factors: age, menopausal status,
      histological and nuclear grading, tumor diameter, node metastases, stage,
      estrogen and progesterone receptors (ER, PR), as well as ploidy and S phase
      fraction. 3) And third to evaluate the effect of flow cytometry and hormone
      receptors on the response to neoadjuvant chemotherapy in stage IIIB and IV
      patients. MATERIAL AND METHODS: The series is composed of 150 patients with
      primary invasive breast cancer (149 females and one male), diagnosed at the St
      George Hospital Pathology Department and in whom an evaluation of the hormone
      receptors and a measuring, by flow cytometry, of ploidy and S phase fraction
      (SPF) were performed. Among them, 68 were followed for a mean period of 45
      months. The disease free survival and the overall survival were recorded as well
      as the response to neoadjuvant chemotherapy. RESULTS: The authors did not find
      any statistically significant difference in survival between diploid and
      aneuploid tumors, tumors with SPF above and below 8%, those who are ER+ and ER-
      and those who are PR+ and PR-. But it seemed that diploid, low SPF and positive
      hormone receptors tumors had a tendency toward a better disease free survival.
      The multivariate analysis using the Cox proportional hazards identified the tumor
      diameter as being the only independent prognostic factor (p = 0.046). The nuclear
      grade reached a limit of significance (p = 0.08). Diploidy, low SPF and
      positivity of ER and PR were associated one to the other and to low histologic
      and nuclear grades. Finally, neither flow cytometry parameters nor hormone
      receptors were predictive of a susceptibility to neoadjuvant chemotherapy.

PMID- 10881438
TI  - Comparative study of antituberculous drug resistance among Mycobacterium
      tuberculosis isolates recovered at the American University of Beirut Medical
      Center: 1996-1998 vs 1994-1995.
AB  - PURPOSE: To study the overall current prevalence of antituberculous drug
      resistance among M. tuberculosis isolates recovered at the American University of
      Beirut Medical Center (AUBMC) between 1996-1998 in comparison to those reported
      on isolates recovered in 1994-1995. MATERIALS AND METHODS: Seventy-four
      consecutive M. tuberculosis isolates recovered from the same number of newly
      diagnosed cases of tuberculosis (TB), between January 1996 and December 1998
      (referred to as 1998), were tested against isoniazid (INH), rifampicin (RIF),
      streptomycin (STM) and ethambutol (ETH), using the BACTEC-TB susceptibility
      procedure and system. The results were compared to those reported on the isolates
      recovered in 1994-1995 (referred to as 1995). RESULTS: A comparison between the
      results obtained in 1998 vs 1995 showed the following, respectively: The male to
      female ratio was 3.1:1 vs 2:1 and the mean ages were almost similar in males,
      33.4 vs 34.1 years but were slightly higher in females 38.2 vs 32.7 years.
      Children (< or = 15 yrs) represented 10.8% vs 8.3% of the study population. The
      prevalence of resistance, to one or more drugs, was almost the same, 24% vs 26%
      but the overall percentages of single drug resistance were generally higher in
      1998 vs 1995 against all the tested drugs except INH: INH (20.2% vs 23.9%), RIF
      (16.2% vs 12.5%), STM (13.5% vs 7.3%) and ETH (8.1% vs 3%). Among the resistant
      isolates, the profiles of resistance indicated decrease in resistance to one and
      two drugs, 6.7% vs 11.5% and 5.4% vs 10.4%, respectively, but showed increase in
      resistance to three and four drugs, 8.1% vs 2.1% and 4% vs 2.1%, respectively.
      Increase in resistance to two or more drugs was also observed, 17.6% vs 14.6%,
      and the prevalence of multidrug resistance, defined as resistance to at least
      both INH and RIF, was also increased, 14.7% vs 11.4%. CONCLUSIONS: This study
      shows a high prevalence and persistence of TB drug resistance tested in our
      Medical Center in Lebanon. In addition, the shift in the increase of resistance
      from one and two drugs to three and four drugs are very ominous and should be
      considered when treating patients in this country. Moreover, such information
      calls for scrutinizing the existing local TB control programs as part of the
      global efforts to minimize the incidence of this highly morbid infectious
      disease.

PMID- 10881439
TI  - Craniofacial anthropometric measurements in a population of normal Jordanian
      newborns.
AB  - Anthropometric measurements provide quantitative values for qualitative
      descriptions, thus playing an important role in the evaluation of individuals
      with dysmorphic features for the identification of patterns of dysmorphism.
      Normative standard values and curves are needed for the meaningful interpretation
      of individual measurements. The available normative standards vary mainly due to
      differences in the populations studied. We obtained 13 different craniofacial
      anthropometric measurements on 158 newborns from Jordan within the first 24 hours
      of birth. We excluded few newborns for selected measurements based on preset
      exclusion criteria. We calculated means and standard deviations and constructed
      standard curves for each measurement. We here present the clinicians in our
      country, and the surrounding countries as well, with a set of reference values
      and curves and a guide to be used in the evaluation of newborns with dysmorphism.

PMID- 10881440
TI  - [Splenic abscess. A rare pathology requiring a multidisciplinary approach].
AB  - The clinical presentation of the splenic abscess is poorly specific. Its natural
      evolution is often fatal. The three case reports illustrate the difficulty of the
      diagnosis and management of this disease. Ultra sound and C.T. scan are the
      procedures of choice for the diagnosis and follow-up. The choice of the treatment
      depends on the number of abscesses, their volume, and also the presence of
      extrasplenic involvement. Antibiotherapy and interventional radiology have
      modified its therapeutical approach. Although the conservative treatment
      (antibiotherapy, transparietal drainage) is often successful, splenectomy is
      still indicated as a first line treatment, or as a salvage procedure.

PMID- 10881441
TI  - Richter's hernia: an unusual presentation.
AB  - Richter's Hernia is an unusual form of herniation. The incarceration accompanying
      the hernia invariably leads to bowel ischemia. Chronic incarceration of the
      antimesenteric border of the intestine, presenting with a long-standing history
      of signs and symptoms with no dire consequences is unusual. We present a case
      with a typical acute presentation, and the only case we are aware of with a
      chronic incarceration leading to a true diverticulum of the hepatic flexure.

PMID- 10881442
TI  - [Kimura disease. Apropos of a case with review of the literature].
AB  - Kimura's disease is an uncommon chronic inflammatory disease of unknown etiology
      often associated with an important category of reactive lymphadenopathy in
      Oriental populations. The enlarged nodes are mostly located in the head and neck
      region. The main pathologic changes in the lymph nodes include florid germinal
      centers, Warthin-Finkeldey polykaryocytes, vascularization of the germinal
      centers, increased postcapillary veinules in the paracortex, eosinophilic
      infiltration and fibrosis. The disease is often confused with angiolymphoid
      hyperplasia with eosinophilia. Because the adenopathy may be the sole
      presentation of the disease, the accurate diagnosis may spare the patients
      unnecessary medical and/or surgical treatment. We report a case of cervical
      lymphadenopathy as a sole presentation of Kimura's disease.

PMID- 10881443
TI  - [Prenatal intestinal invagination. Presentation of a case and review of the
      literature].
AB  - We report a case of intrauterine intussusception in a female newborn. Despite the
      absence of intestinal atresia or any sign of ischemic necrosis, the manual
      reduction of the intussusception was impossible because of the multiple adhesions
      developed in the prenatal period. Laparotomy was done at the age of 10 days, the
      lesion was resected and end-to-end anastomosis was performed. The postoperative
      course was uneventful.

PMID- 10881444
TI  - [Medical confidentiality in Lebanon (I)].

PMID- 10881445
TI  - Hospital readmissions at the communitywide level: implications for case
      management.
AB  - This study describes the development of information concerning the distribution
      of hospital readmissions by diagnosis in seven different United States
      metropolitan areas. The data demonstrated that circulatory disorders were
      associated with the largest number of communitywide readmissions in all of the
      communities. It also showed that circulatory, respiratory, and digestive
      disorders accounted for a majority of readmissions in all of the areas. This
      information suggested that case management efforts to reduce readmissions can
      focus on a limited range of clinical diagnoses. This approach should enable the
      process to function effectively within resource constraints.

PMID- 10881446
TI  - Consensual validation of clinical practice model practice guidelines.
AB  - Clinical Practice Model (CPM) Practice Guidelines facilitate the delivery of
      consistent, high-quality patient care by clarifying nursing services and
      supporting the practice and documentation of each step of the nursing process.
      CPM Practice Guidelines are unique because they are part of an integrated
      interactive systems thinking framework to support professional practice; they are
      reviewed and improved routinely using multiple sources of data and are used by
      hundreds of nurses daily throughout the United States and Canada. Guidelines are
      developed using a rigorous standardized format and process. Consensual validation
      is an important part of establishing and maintaining the credibility of these
      Guidelines.

PMID- 10881447
TI  - Outcomes analysis of a pain management project for two rural hospitals.
AB  - There has been a strong emphasis on effective pain management in recent years,
      yet application of new knowledge and research in the area seems to be implemented
      inadequately. Traditional educational approaches for clinicians must be
      complemented by interventions in health care systems that more directly influence
      the routine behaviors of clinicians. In an effort to address this problem, a
      project was designed to increase institutional commitment to improving pain
      management in two rural hospitals. The purpose of this article is to present the
      change process used and the findings from the program.

PMID- 10881448
TI  - Reducing seclusion and restraint: meeting the organizational challenge.
AB  - The Mohawk Valley Psychiatric Center has experienced a major reduction in the use
      of seclusion and restraint in the past five years. It has used the traditional
      quality improvement (QI) tools like the Plan Do Check Act, Flowcharts, Fishbone
      diagrams, and Parieto Charts as suggested in the QI literature. The original work
      to reduce seclusion and restraint are described in two previous articles by
      Visalli and McNasser. This article describes the additional work since that time.
      The seclusion/restraint rate in adult service per 1,000 patient days is 0.13 for
      restraint and 0.15 for seclusion for calendar year 1998. Children and youth
      service also has comparatively minimal use of seclusion and restraint. The
      success of this program is attributed to the organizational leadership and the
      interdisciplinary approach taken to provide individualized treatment. Many of the
      initiatives stem from a working relationship with patients on how to improve
      customer service.

PMID- 10881449
TI  - Quality of care information for consumers on the Internet.
AB  - The purpose of this study was to assess the readability of quality of care
      information for consumers available on the Internet. Ten Internet resources for
      consumers, found at three major Web sites, were analyzed for readability. The
      scores ranged from a low of 6th grade level for information in the document
      "Quick Checks for Quality: Choosing Quality Health Care" to a high of 12th grade
      level for "Helping You Choose a Quality Ambulatory Care Organization." The
      overall mean reading demands of four of the documents were higher than the 8th
      grade level recommended for the general public. Six of the documents were at this
      level or below, placing them at an appropriate reading level for most consumers
      to understand the information.

PMID- 10881450
TI  - The relationship between staffing and quality in long-term care facilities:
      exploring the views of nurse aides.
AB  - Research on staffing and quality of care in long-term care facilities confirms
      that adequate staffing levels are important to ensuring quality but few studies
      have examined how the two are linked. The research reported in this article used
      participant observation and indepth interviewing to explore how nurse aides (NAs)
      understand the link between staffing and quality. The findings show that NAs deem
      their relationships with residents to be the central determinant of quality of
      care as well as an important outcome in itself. Adequate staffing is essential to
      allowing NAs to nurture these relationships.

PMID- 10881451
TI  - Improving health promotion for blue-collar workers.
AB  - The purpose of the study was to discover factors that may influence blue collared
      workers' participation in health promotion programs. One hundred sixty blue
      collared workers age 18 to 65 completed Laffrey's Health Conception Scale (LHCS)
      and Penders Health Promoting Lifestyle Profile (HPLP). Results indicated: 1.)
      Women scored significantly higher on health responsibility and interpersonal
      support than men; 2.) Older workers scored significantly higher on nutrition,
      while younger workers scored significantly higher on exercise; 3.) Older workers
      scored significantly higher on role and self-actualization than younger workers;
      and 4.) A significant relationship exists between health conception and health
      promoting life style. Gender, age, and the individual definition of health are
      important when planning health promotion programs at industrial sites.

PMID- 10881452
TI  - Rural economic development vs. tobacco control? Tensions underlying the use of
      tobacco settlement funds.
AB  - Some public health advocates in tobacco states, having reconsidered the impacts
      of the federal tobacco price-support program, have negotiated common tobacco
      regulatory policy stances with tobacco grower representatives. This paper
      describes the impact of this rapprochement on the state-level negotiations of
      Master Settlement Agreement funds. It argues that there are indeed two worthy
      public health goals: tobacco control and the economic viability of tobacco
      dependent communities (TDCs), but the immediacy of the threat to the latter, the
      political potency of tobacco growers, and growers' goal of maintaining tobacco as
      their farms' anchor bring severe risks to the tobacco control portion of
      Settlement funds. Among three competing philosophies of economic development for
      TDCs, none are well evaluated, and two potentially create endless demands on
      Settlement resources. Public health policy advocates are urged to participate in
      negotiations on TDC economic development and to forcefully advocate for adequate
      tobacco control resources.

PMID- 10881453
TI  - The impact of cannabis decriminalisation in Australia and the United States.
AB  - This paper summarises and compares the impacts of cannabis decriminalisation
      measures in two countries. In Australia, an expiation model of decriminalisation
      succeeded in avoiding the imposition of criminal convictions for many offenders,
      but substantial numbers of offenders received criminal convictions because of a
      general "net-widening" in cannabis offence detections, and the failure of many
      offenders to pay expiation fees and thus avoid criminal prosecution. Despite
      these problems, the expiation approach has been cost-effective, reducing
      enforcement costs without leading to increased cannabis use. In the United
      States, cannabis decriminalisation similarly reduced enforcement costs, with
      enforcement resources generally redirected toward trafficking and other illicit
      drugs. There were no increases in cannabis use or substantial problems that could
      be ascribed to decriminalisation. The implications for other countries are
      discussed, with particular attention to the importance of implementation issues,
      monitoring, and evaluation. Although decriminalisation has succeeded in reducing
      enforcement and other costs without increasing the problems associated with
      cannabis use, the same impacts would not necessarily result from the legalisation
      of cannabis or the decriminalisation of other illicit drugs.

PMID- 10881454
TI  - Prescriptions, power and politics: the turbulent history of methadone maintenance
      in Canada.
AB  - Illicit opiate addiction has emerged as a major problem in many Western countries
      in the second half of this century, and its social harm implications have become
      much exacerbated with the onset of the HIV epidemic in the 1980s. By now, most
      Western jurisdictions have resorted to methadone treatment as the most effective
      and best researched intervention against the negative consequences of opiate
      addiction including mortality, morbidity, crime, and loss of social functioning.
      Methadone treatment in Canada features a long, turbulent, and instructive history
      as an exemplary case study in public policy. While both Britain and the U.S.
      experimented with opiate prescription treatment in the first half of the century,
      Canadian proposals for such programs initially never made it beyond the
      discussion stage, largely due to the influential resistance from the law
      enforcement sector. However, in light of growing influence from an emerging
      addictions treatment sector, Canada became the first Western jurisdiction to
      experiment with methadone prescription for the treatment of opiate addiction
      forty years ago. Methadone treatment became quickly and widely established as an
      effective treatment modality through the 1960s. But in the early 1970s,
      resistance from the law and health sectors evolved, and triggered the government
      to establish a set of comprehensive and restrictive federal methadone treatment
      regulations, which have dominated its realities until today. Almost completely
      regulated out of existence by the end of the 1970s, methadone treatment's
      prevalence gradually increased again through the 1980s, and recent
      decentralization efforts to provincial levels earlier this decade have had
      dramatic effects on treatment availability. Significant events in the Canadian
      history of methadone treatment and its regulation reflect developments in the
      U.S., and substantial recent domestic treatment expansion developments--as well
      as renewed sparks of resistance--are reminiscent of methadone treatment's
      patterns of history as they developed in the late 1960s. This paper traces the
      turbulent history of methadone treatment, regulation and policy in Canada with
      particular attention to institutional, professional and political determinants at
      the complex intersection of health, law, and addiction.

PMID- 10881455
TI  - Mixed prognosis: equity, access, and emerging issues within British Columbia's
      health care system.
AB  - The author, an American, examines British Columbia's health care system as it
      struggles to retain equity and access as two of its implacable tenets. Some
      sources argue that realities fall far short of the abstract ideals. Certainly
      implementation and funding problems are growing as B.C.'s policy makers struggle
      with large-scale economic pressures and management priorities. Despite the
      system's shortcomings, however, U.S. readers would be wise to consider the
      philosophical and rhetorical impact of these normative concepts. Their presence
      and power encapsulates the breadth of the contrast between the Canadian and
      American systems.

PMID- 10881456
TI  - Variations in teenage activities with and without a driver's license.
AB  - High school students were surveyed every 6 months from their freshman through
      senior years concerning licensing, driving, and transportation to and from their
      various activities. Students in Delaware (learner's permit can be issued at age
      15 years, 10 months; driver's license at age 16) were compared with students in
      Connecticut and New York (permit at age 16; license at age 16) and in New Jersey
      (license at age 17). During the junior year, most Delaware students, some New
      York and Connecticut students, and few New Jersey students were licensed.
      However, even during the junior year, students in the respective states did not
      differ significantly with respect to time spent at activities such as a paying
      job, homework, watching television, dating, parties, being with friends, talking
      on the phone, or participating in sports or school activities. Graduated
      licensing systems can delay full-privilege teenage licensure and reduce teenage
      crash rates. These systems also can increase the number of times parents and
      others must drive. However, the present study's results indicate that licensing
      delays of as much as 1 year have minimal effects on the nondriving activities of
      high school students.

PMID- 10881457
TI  - Podiatric medical research.

PMID- 10881458
TI  - Analysis of release of the first branch of the lateral plantar nerve.
AB  - The authors conducted a retrospective study of the release of the first branch of
      the lateral plantar nerve in the treatment of chronic heel pain unrelieved by
      conservative treatment modalities. A total of 17 patients (18 feet) were
      evaluated following external neurolysis for heel pain caused by entrapment of the
      first branch of the lateral plantar nerve. The average postoperative follow-up
      time was 32.8 months, with a range of 10 to 72 months. Every patient deemed the
      surgery successful. At the time of follow-up examination, nine feet were
      asymptomatic and nine feet experienced mild pain after extended activity. There
      was one postoperative complication, medial calcaneal nerve entrapment; it was
      successfully treated with neurectomy.

PMID- 10881459
TI  - Use of electrostimulation in the treatment of diabetic neuroarthropathy.
AB  - Charcot's joint is a difficult and sometimes frustrating condition to treat, for
      both the patient and the physician. The authors give a brief overview of
      Charcot's joint and the treatment options available. They discuss the use of bone
      stimulators and how electrostimulation may be used to help arrest the progression
      of Charcot's deformity. To the authors' knowledge, the use of electrostimulation
      for the treatment of Charcot's joint has been described only once in the
      literature; three patients were evaluated in that study. In the current study, 11
      patients were evaluated, with promising results obtained, thus supporting the
      findings of the previous study.

PMID- 10881460
TI  - Normal values of plantar pressure measurements determined using the EMED-SF
      system.
AB  - Plantar pressure-measurement technology is being increasingly used by podiatric
      physicians and surgeons in both clinical practice and research. The authors
      present normal reference-range values for peak pressure, mean pressure, and
      pressure-time integral obtained from 30 healthy subjects using a two-step
      recording technique and the EMED-SF system, as background for proposed clinical
      trials. Normative data of this type are essential for clinical practice in the
      comparison of plantar pressure-measurement values of individual patients with
      those of normal, asymptomatic feet.

PMID- 10881461
TI  - Levels of evidence of articles in podiatric medical journals.
AB  - The authors reviewed 322 articles in podiatric medical journals to determine
      their level of evidence. Only 1% of the articles reviewed were randomized
      controlled trials. The authors concluded that if the podiatric medical profession
      wishes to become a participant in evidence-based medicine, greater emphasis must
      be placed on studies that assess hypotheses.

PMID- 10881462
TI  - First metatarsophalangeal joint implant as a salvage procedure.
AB  - First metatarsophalangeal joint implants are used to correct deformity, to
      restore or improve motion, and to relieve pain. The authors report on a patient
      with pain in the first metatarsophalangeal joint that was not relieved by
      multiple first metatarsophalangeal joint surgical procedures. A two-component
      first metatarsophalangeal joint titanium implant was successfully used as a
      salvage procedure to relieve pain and restore foot function following a failed
      first metatarsophalangeal joint fusion.

PMID- 10881463
TI  - Squamous cell carcinoma of the hallux.
AB  - This article reports on a case of malignant degeneration of a hallux nail bed
      ulcer of 30 years' duration. Histologically, this lesion was determined to be a
      squamous cell carcinoma, a type of lesion that is also known as Marjolin's ulcer.
      The diagnosis, histologic findings, and treatment of patients with cutaneous
      squamous cell carcinoma are discussed.

PMID- 10881464
TI  - A conceptual model for a geriatric fellowship in podiatric medicine.
AB  - The number of older individuals living in the United States is projected to
      increase significantly over the next few decades. To help meet the health-care
      needs of this growing population, podiatric medicine must assure the public of
      the availability of specially educated teachers and practitioners who can not
      only provide direct patient care, but also participate in establishing national
      policies and priorities pertaining to foot health. Fellowship training, the
      traditional educational model beyond the first professional degree and residency
      education, is one means of accomplishing this goal. This article proposes a model
      for a geriatric fellowship in podiatric medicine. Implementation of such
      fellowship training in geriatrics can help the podiatric medical profession
      pursue its mission and fulfill its responsibility to the public.

PMID- 10881465
TI  - Skin grafting of partial-thickness burns in the diabetic foot.

PMID- 10881466
TI  - Foot deformities associated with Apert syndrome.

PMID- 10881467
TI  - Use of a clonidine patch in the treatment of ischemic ulcerations of the foot.

PMID- 10881468
TI  - Acral-lentiginous melanoma.

PMID- 10881469
TI  - Diabetes among key health priorities for NMA.

PMID- 10881470
TI  - Intergenerational effects of high socioeconomic status on low birthweight and
      preterm birth in African Americans.
AB  - As socioeconomic status (SES) increases, the incidence of low birthweight and
      preterm birth decreases irrespective of social class. However, low birthweight
      remains twice as high for African-American women as for white women even when SES
      is controlled. This study examines to what extent second generation high SES
      African-American women experience improvement in birthweight and gestational age.
      One hundred eighty-nine former Meharry students were surveyed. Identified were
      934 births that are the children and grandchildren of these students who
      matriculated at Meharry. These infants are compared with a cohort of white
      mothers from a study in the School of Public Health at Yale University. Low
      birthweight was reduced in the third generation high SES African-American
      children (6.9%) from the second generation (11.4%) but remained higher than white
      children (3.3%). Results showed that African-American third generation children
      remained at higher risk for low birthweight than were white children (relative
      risk [RR], 1.78; 95% confidence interval [CI], 1.03, 3.09). Similar results were
      observed for preterm delivery where the increased risk to third generation
      African-American children was 3.16 (1.89, 5.27). Persistent strong ethnic
      differences in birthweight in this high SES cohort (OR = 3.16, 95% CI, 1.89-5.27)
      support a conclusion that African-American women have birthweight distributions
      that are somewhat lighter than white women. This may explain a portion of current
      ethnic differences in birthweight. It is also possible that persistent
      psychosocial and behavioral factors continue to negatively influence birthweight,
      even in second generation high SES African-American mothers. This explanation
      will require identification of powerful risk factors, which are largely unrelated
      to those presently under investigation.

PMID- 10881471
TI  - Colorectal cancer: update on recent advances and their impact on screening
      protocols.
AB  - As the third leading cause of cancer cases and deaths in the United States,
      colorectal cancer has been an area of intense interest. The objectives of this
      article are, through a review of the literature published between 1995 to 1998,
      to examine current trends in the epidemiology of colorectal cancer, new
      information on genetic, dietary, and other risk factors; to evaluate the
      effectiveness of current screening guidelines for various populations; to review
      information on chemoprevention; and finally to examine new concepts on the
      horizon in the area of colorectal cancer research. Much of the recent research in
      the field has focused on etiology, dietary, and other risk factors. Many genetic
      factors have been discovered, which serve to elucidate the mechanism of
      pathogenesis of colorectal cancer as well as offer possible targets for treatment
      strategies. Dietary and risk factors for colorectal cancer may pave the way for
      chemoprevention. In light of the most recent information on colorectal cancer,
      one is able to more accurately assess current screening guidelines for their
      effectiveness in all populations based on epidemiologic data, as well as evaluate
      more novel screening strategies for their possible utility in the future. In
      addition to a review of the most up-to-date literature, the authors also provide
      their recommendations for screening based on the evidence in which the review of
      the literature provides. Finally, current and future treatment options are
      discussed. It is our hope that the physicians will find this review useful in the
      evaluation and care of patients at risk of developing colorectal cancer.

PMID- 10881472
TI  - Racial variation in wanting and obtaining mental health services among women
      veterans in a primary care clinic.
AB  - Epidemiologic studies suggest that African-American women may be less likely to
      obtain mental health services. Racial differences were explored in wanting and
      obtaining mental health services among women in an equal access primary care
      clinic setting after adjusting for demographics, mental disorder symptoms, and a
      history of sexual trauma. Participating in the study were women veterans at a
      primary care clinic at the Durham Veterans Affairs Medical Center. Consecutive
      women patients (n = 526) between the ages of 20 and 49 years were screened for a
      desire to obtain mental health services. Patients were given the Primary Care
      Evaluation of Mental Disorders questionnaire (PRIME-MD) and a sexual trauma
      questionnaire. Mental health service utilization was monitored for 12 months. The
      median age of the women was 35.8 years; 54.4% of them were African-American.
      African-American women expressed a greater desire for mental health services than
      whites, yet mental health resources at the clinic were similarly used by both
      racial groups. African-American women may want more mental health services;
      however, given an equal access system, there were no racial differences in mental
      health use.

PMID- 10881473
TI  - Factors related to noncompliance with screening mammogram appointments among low
      income African-American women.
AB  - Despite current mammography recommendations, screening rates among African
      American women are suboptimal. The purpose of this case-control study was to
      identify the psychological, demographic, and health care system barriers to
      screening mammography use among low-income African-American women. A total of 574
      women with screening mammogram appointments at an urban hospital were interviewed
      to determine the predictors of mammogram appointment noncompliance. Predictor
      variables included: demographics; breast cancer knowledge, attitudes, beliefs,
      and screening practices; and type of health care provider making the referral.
      Age was inversely related to mammogram appointment noncompliance. Relative to
      women 40 to 49 years old, women 70 years of age and older were the least likely
      to miss their appointments (odds ratio [OR], 0.3; 95% confidence interval [CI],
      0.2, 0.5). Women referred for mammography by a physician's assistant or nurse
      practitioner were less likely to miss their appointments than women referred by a
      physician (OR, 0.3; 95% CI, 0.1, 0.8). Embarrassment, lack of breast symptoms,
      and forgetfulness also contributed to noncompliance. Key demographic,
      attitudinal, and health care system factors hinder low-income African-American
      women from obtaining screening mammograms. These findings have significant health
      education and policy implications for health care delivery to women in this
      population.

PMID- 10881474
TI  - Assessment and management of the violent patient.
AB  - This article provides guidance on how to manage the unavoidable challenge of
      aggression in psychiatric relationships. Accordingly, this article addresses
      issues of personal safety and how to manage potentially violent patients, defuse
      situations that threaten imminent violence, and manage emergent violence. In
      addition, a useful chart is highlighted that differentiates different types of
      violence.

PMID- 10881475
TI  - Otalgia in children.
AB  - Otalgia is a common symptom in the pediatric age group. The most common cause is
      acute otitis media, followed by otitis externa. In the majority of cases, the
      diagnosis can be established by a thorough history and a careful otologic
      examination. When the otologic findings are normal and the etiology is obscure, a
      thorough work-up to determine the source of referred pain is essential.
      Laboratory investigations are usually not necessary. Treatment should always be
      directed at the underlying cause.

PMID- 10881476
TI  - Case presentation: Sturge-Weber Syndrome.

PMID- 10881477
TI  - Bacterial endocarditis and orthodontics.
AB  - The purpose of this article is to discuss the prevalence and intensity of
      bacteraemia associated with orthodontic procedures and help formulate practical
      guidelines for orthodontists treating children with congenital or acquired heart
      disease. Preliminary results demonstrate a significant increase in the intensity
      of bacteraemia from baseline following insertion of an orthodontic separator. The
      potential for development of bacterial endocarditis (BE) is extremely low,
      questioning the need for antibiotic prophylaxis for procedures other than
      extractions. However, for patients who are 'at risk' a very high standard of oral
      hygiene is essential and much of the responsibility lies with the individual
      patients to learn to protect themselves.

PMID- 10881478
TI  - Correlating clinical appearance of nasopharyngeal carcinoma with tumour staging.
AB  - Since there is a tendency for nasopharyngeal carcinoma (NPC) to exhibit sub
      mucosal spread and endophytic growth, it would be useful to know if NPC remained
      inconspicuous in the post-nasal space (PNS) even in advanced stages of disease.
      The aim of this study was to find out if there was a correlation between tumour
      appearance in the PNS and tumour stage. One hundred and twenty-two consecutive
      patients with NPC were studied. The appearance of a tumour in the PNS was
      classified as to whether or not it was obviously malignant-looking (via naso
      endoscopy). Tumour stagings were undertaken according to computerised tomography
      (CT) scan findings. Of the patients studied, 67 (54.9%) had obvious malignant
      looking lesions. Tumour appearance was found to correlate with tumour-staging (p
      = 0.023, chi-squared test). There was, therefore, a tendency for early tumours to
      present as inconspicuous or innocuous-looking lesions, whereas advanced tumours
      tended to appear as obvious malignant-looking lesions in the PNS. The clinical
      significance of these findings is discussed.

PMID- 10881480
TI  - Anorectal malformations in female children--10 years experience.
AB  - Despite enormous interest in the development of an ideal operative procedure to
      treat anorectal malformations, the situation is as confusing as it was 30 years
      ago. The reasons could be inconsistency of the nature of the lesions found in
      patients along with multi-system associated malformations primarily affecting the
      prognosis of available procedures. High imperforate anus is a complex anomaly
      that requires a combination of careful preservation of structures and precise
      anatomic reconstruction for optimal results. A retrospective study, comprising a
      consecutive sample of female children with anorectal malformations treated over a
      period of 10 years, is presented. Of 130 patients, 83% (n = 108) presented later
      than 3 months of age as they could pass stools through associated fistulae, of
      which the commonest type was found to be an ano- or recto-vestibular fistula
      (65%, n = 83). Ninety-four cases (72%) had what are traditionally known as "low"
      anorectal malformations (perineal fistulae, anteriorly placed anus and anorecto
      vestibular fistulae). Ten percent (n = 14) had translevator, and 17% (n = 22)
      were found to have "high" lesions. Seventeen percent of patients (n = 22) had
      associated congenital malformations, predominantly in intermediate and high
      anorectal lesions, 40% of which pertained to the urogenital system. In total, 137
      definitive operative procedures were done including Mollard's anterior perineal
      approach in 81 patients and posterior sagittal anorecto plasty (PSARP) in 38,
      enabling a comparison to be made of the functional results and complications in
      the two groups. Out of 24 post-operative complications noted in the series, 17
      were found in the group who had Mollard's procedure carried out (including 3
      deaths) as compared with 7 in these cases who had PSARP (two-sided P utilizing
      Fisher's exact test = 0.475).

PMID- 10881479
TI  - The effects of splenic artery ligation in an experimental model of secondary
      hypersplenism.
AB  - OBJECTIVE: To induce hypersplenism in rats by splenic vein ligation and to
      investigate the effects of splenic artery ligation in this model. BACKGROUND:
      Selective arterial embolisation and splenic artery ligation (SAL) are used in the
      treatment of secondary hypersplenism in some medical centres but these methods
      are not common. MATERIALS AND METHODS: Thirty male Saprague-Dawley rats were
      allocated to three groups (n = 10). The first group underwent laparotomy, the
      second and third groups underwent laparotomy and splenic vein ligation. At the
      end of the third week, laparotomy was performed in the first and second groups
      and splenic artery ligation in the third group. Erythrocyte, leukocyte and
      platelet counts were performed weekly. At the end of the sixth week, the animals
      were sacrificed and the spleens were taken for histopathologic examination.
      RESULTS: In the second and third groups, after splenic vein ligation, the
      erythrocyte and platelet counts were significantly reduced at the end of the
      second week (p < 0.01). In the second group, which underwent splenic vein
      ligation only, the levels remained low throughout the experiment. In the third
      group, after splenic artery ligation, there were rises in both erythrocyte and
      platelet counts; the levels were similar to the levels in the control group at
      three weeks after splenic artery ligation (p > 0.05). No significant changes were
      observed in the leukocyte counts throughout the experiment (p > 0.05).
      CONCLUSIONS: Splenic vein ligation successfully induces experimental secondary
      hypersplenism. This state can be ameliorated by splenic artery ligation.

PMID- 10881481
TI  - Thoracoscopy versus open lung biopsy in the diagnosis of interstitial lung
      disease: a randomised controlled trial.
AB  - BACKGROUND: Some patients with diffuse lung disease require a lung biopsy for
      diagnosis. This study is aimed to compare the clinical results and the efficacy
      of video-assisted thoracoscopic lung biopsy with the open lung biopsy method for
      the diagnosis of interstitial lung disease. From January 1996 to December 1998,
      61 patients were referred for diagnostic lung biopsy. Thirty two patients were
      randomly allocated to have a thoracoscopic lung biopsy and twenty nine had an
      open lung biopsy. Subsequently, various factors were analyzed and compared in
      both groups. RESULTS: There was no difference between the groups in age and
      pulmonary function test. Median operative time was 45 minutes for the
      thoracoscopic biopsies and 60 minutes for the open biopsies (P = 0.009). Median
      amount of analgesia (Demerol) in the first 24 hours postoperatively was 75 mg.
      for thoracoscopic biopsies and 150 mg. for open biopsies (P < 0.001). Median
      duration of insertion of a chest tube in days and 24 hours of pleural drainage
      was not statistically significant between the two groups. Duration of hospital
      stay was significantly less for the thoracoscopic biopsy (3 days) compared with
      an open biopsy (5 days) (P < 0.001). The diagnostic yield of each method was
      comparable (thoracoscopic biopsy 31/32; open biopsy 27/29) (P = 0.3).
      Complications occurred in 6/29 of patients undergoing open biopsies and 3/32
      patients undergoing thoracoscopic lung biopsies (p = 0.28). There were 2 deaths
      among patients who had an open lung biopsy. CONCLUSION: Thoracoscopic lung biopsy
      has some clinical advantages over open biopsy. These findings suggest that
      thoracoscopic lung biopsy is an acceptable alternative to open lung biopsy for
      the diagnosis of diffuse interstitial lung diseases.

PMID- 10881482
TI  - Centralisation of oesophageal cancer services; the view from the periphery.
AB  - There is debate as to whether patients requiring resection for oesophageal cancer
      should be referred to specialist centralised units rather than being managed by
      general surgeons in district general hospitals (DGH). The aim of this study was
      to determine the effects of centralising oesophageal cancer surgery on outcome
      and quality of service for patients with oesophageal cancer in a peripheral
      region. Patients with biopsy proven oesophageal cancer diagnosed over a 4 year
      period were identified from pathology records. Patients were divided into two
      groups; Group 1 (n = 60) from the first two years of the study who had any
      surgery performed by a general surgeon within the DGH and Group 2 (n = 53) from
      the latter two years of the study who had any surgery performed in a regional
      cardiothoracic unit. The post-operative mortality rate was lower in the
      specialist unit, 5.6% vs. 12.5%, but this was not statistically significant.
      There were no significant differences in survival rates; 3 month, 1 year, 2 year
      and 3 year survival rates were 63% vs. 62%, 24% vs. 25%, 12% vs. 8% and 7% vs. 6%
      in Groups 1 and 2, respectively. Referral rates for a surgical opinion were
      significantly lower in Group 2--92% vs. 63% p < 0.01 by Chi-squared test.
      Patients waited significantly longer from diagnosis to definitive treatment in
      Group 2--median 15 days vs. 23 days p = 0.17 by Mann-Whitney test. In conclusion,
      survival rates are not necessarily improved by centralisation of oesophageal
      cancer surgery and quality of service may be poorer.

PMID- 10881483
TI  - Glyceryl trinitrate treatment of chronic fissure in ano: one year's experience
      with 0.5% GTN paste.
AB  - OBJECTIVE: Assessment of the efficacy of topical 0.5% glyceryl trinitrate (GTN)
      paste in the treatment of chronic fissures in ano. PATIENTS AND METHODS: Forty
      five patients were treated with 0.5% GTN paste and reviewed at 3, 6 and 12 weeks
      to assess symptoms, side effects and fissure healing. RESULTS: At 6 weeks, 73% of
      patients had no fissures. In 27% of cases treatment was unsuccessful. At three
      month follow up there was no early recurrence. The prevalence of headaches was
      84% with 11% headache related non-compliance. CONCLUSIONS: The use of 0.5% GTN
      induces rapid healing of chronic anal fissures with a 73% healing rate in this
      study. Successful treatment may come at the expense of a high incidence of
      headaches and a lower compliance than found in studies involving a lower
      concentration of GTN. A balance is required between fissure healing and headache
      intolerance.

PMID- 10881484
TI  - Abdominal aortic aneurysms.

PMID- 10881485
TI  - Sepsis and the systemic inflammatory response syndrome.
AB  - Sepsis and the systemic inflammatory response syndrome are common and represent a
      major factor in morbidity and mortality in intensive care units and the
      critically ill. The pathogenesis of these syndromes is becoming increasingly
      understood and it is hoped that this will result in improved outcome. However,
      novel treatments have so far failed to live up to the expectations following
      extensive and promising in vitro and in vivo animal studies. The aim of this
      review is to detail the currently used definitions of systemic inflammatory
      response syndrome, sepsis and septic shock and to present an overview of our
      current understanding of the pathophysiology which underline these conditions.

PMID- 10881486
TI  - Deaths following hernia surgery: room for improvement.
AB  - BACKGROUND: Abdominal wall herniae are common and may well lead to death. The aim
      of this study was to examine the deaths of patients with an inguinal, femoral or
      incisional hernia to identify aspects of management which could be improved upon.
      METHOD: Data collected by the Scottish Audit of Surgical Mortality 1994-1997 was
      analysed by interrogation of the database for all deaths on a surgical ward or
      within 30 days of surgery where the principle diagnosis was inguinal, fermoral or
      incisional hernia. RESULTS: There were 133 deaths out of 31,525 operations over
      the 4-year period. Mortality was highest among femoral hernia operations in women
      (37 deaths/1184 operations; 3.1%) and 59% of femoral hernia surgery was performed
      outwith normal working hours. The 133 patients were elderly (mean age 79 years)
      and unfit, but less than half the operations involved consultant anaesthetists or
      consultant surgeons. Delay in referral contributed to death in 15/133 patients
      and adverse factors in management, particularly in the perioperative period,
      caused the death of 2 patients and contributed to the death of a further 29/133.
      CONCLUSIONS: Herniae carry a significant mortality in elderly, unfit patients who
      require close attention to perioperative management. These patients should be
      anaesthetised and operated upon by consultant staff during the normal working
      day.

PMID- 10881487
TI  - A modification to aid open tracheostomy.
AB  - Open tracheostomy is performed less frequently thereby increasing the likelihood
      of morbidity, e.g. bleeding. The simple modification described aids the technical
      process and minimises problems with the procedure.

PMID- 10881488
TI  - A case of multiple splenic abscesses managed non-operatively.
AB  - We report the case of a previously fit 22-year-old man who developed multiple
      splenic abscesses of unclear aetiology and was successfully treated with
      percutaneous drainage of the largest abscess and antibiotic therapy.

PMID- 10881489
TI  - Extracranial neurilemmoma: a case report and review of the literature.
AB  - A 14-year-old male presented with a several month history of an asymptomatic
      right cervical swelling. An ultrasound scan showed a solid lesion superficial and
      superior to the thyroid gland. Surgical excision of the lesion was carried out
      and histological examination revealed a neurilemmoma. Neurilemmomas are
      relatively rare tumours and even rarer in children. The incidence of such tumours
      and the management of our patient are discussed.

PMID- 10881490
TI  - A case of a Spigelian hernia at an unusually high anatomical location.
AB  - Most Spigelian hernias occur below the level of the umbilicus close to the level
      of the arcuate line. We report a case diagnosed by computed tomography in an
      unusually high anatomical location due to a previous drain site incision.

PMID- 10881491
TI  - Mediastinal endodermal sinus tumour: surgical role in chemotherapy resistant
      cases.
AB  - We report two cases of aggressive mediastinal endodermal sinus tumours (EST)
      detected incidentally on a chest radiograph. The patients were being investigated
      for minor chest complaints. After three courses of cisplatin-based chemotherapy
      the tumour marker levels declined. However, the tumour size continued to
      increase. Complete surgical removal was possible in one case and significant
      reduction in tumour mass was achieved in the other. Reduction in the viable,
      tumour tissue load made the residual tumour sensitive to postoperative
      chemotherapy. It is important to be aware of endodermal sinus tumours refractory
      to chemotherapy which may require early surgical intervention.

PMID- 10881492
TI  - Revalidation: the catalyst for change in continuing professional development?

PMID- 10881493
TI  - Would measurement of C-reactive protein reduce the rate of negative exploration
      for acute appendicitis?

PMID- 10881494
TI  - Would measurement of C-reactive protein reduce the rate of negative exploration
      for acute appendicitis?

PMID- 10881495
TI  - Hydatid liver disease as a cause of recurrent pancreatitis.

PMID- 10881496
TI  - The management of femoral and tibial diaphyseal fractures.

PMID- 10881497
TI  - Radical cystectomy and ileal conduit for invasive bladder tumour.

PMID- 10881498
TI  - American Society of Anaesthesiologist Physical Status (ASA-PS): a predictor of
      treatment outcome of transurethral resection of the prostate (TURP)

PMID- 10881499
TI  - [Contribution of military and civil medicine to the victory in the Great
      Patriotic War].

PMID- 10881500
TI  - [Biochemical markers of myocardial lesion].

PMID- 10881501
TI  - [Etiotropic combined therapy of HIV-infection].

PMID- 10881502
TI  - [Current trends in the treatment and outcome of acute myocardial infarction
      (MI)].
AB  - Current trends in the treatment and outcome of acute myocardial infarction were
      studied in a trial entering 2411 patients with macrofocal myocardial infarction
      (MI) treated in 1993-1998. There were many cases of severe and repeated MI. The
      age of the patients tends to increase. Lethal outcomes' probability is very high
      in multiple stenosis of the coronary arteries. This condition is associated with
      a high risk of cardiac insufficiency progression because of inadequate blood
      supply to necrosis-free myocardial zones. Thrombolytic therapy (TLT), ACE
      inhibitors reduce lethality but their use is limited by such factors as
      concurrent diseases, time from MI onset, rethrombosis risk. As a result, only 1/5
      of the patients received pharmacological treatment. Balloon angioplasty is
      indicated in contraindications to TLT, in TLT failure or large residual stenosis.
      ACE inhibitors slow down the progression of cardiac insufficiency giving time for
      surgical revascularization. Updated treatment of MI improved its outcomes, but
      further progress in lowering MI lethality will be insignificant unless efficient
      methods providing adequate blood supply to the myocardium are introduced.

PMID- 10881503
TI  - [Dynamics of indices of peripheral circulation as one of the prognostic criteria
      in acute myocardial infarction].
AB  - The results of our investigations demonstrate that significant differences exist
      in peripheral hemodynamics of patients with severe and more favourable course of
      acute myocardial infarction. This can be explained by different types of
      hemodynamics. Thus, such parameters as arterial inflow and venous outflow can
      serve prognostic factors of acute myocardial infarction.

PMID- 10881504
TI  - [Clinical functional aspects of cardiac activity and vegetative imbalance in
      dumping syndrome].
AB  - Programmed computer transesophageal pacing with pharmacological heart denervation
      by A. Jose and D. Collinson, mathematical analysis of cardiac rhythm according to
      spectral and statistical methods were used in the study of extra-abdominal
      (cardial and vegetative) manifestations of dumping syndrome (DS)--one of severe
      complications of ulcer surgery. Serotoninemia was assessed by enzyme immunoassay
      (DRG kit). It was established that cardial and vegetative disorders are typical
      for DS patients and correlate with severity of motor defects of the
      gastrointestinal zone as well as fasting serotonin levels. Cardiac arrhythmias in
      DS in most cases are associated with functional insufficiency of pacemakers. This
      requires caution in administration of antiarrhythmic drugs in DS patients.

PMID- 10881505
TI  - [Diagnostic difficulties in lower-lobe tuberculosis].
AB  - Lower lobe tuberculosis is diagnosed more frequently than tuberculosis of the
      superior lobe in subjects seeking medical advice. Clinical improvement achieved
      by nonspecific antibacterial therapy should not diminish the alertness of the
      physicians to tuberculosis. When making diagnosis it is necessary to take into
      consideration: duration of the disease, relatively satisfactory condition in
      advanced process, negative x-ray picture, contact with tuberculosis patients.
      Multiple examinations of the sputum for M. tuberculosis are recommended.

PMID- 10881506
TI  - [Acid-base balance in ulcer patients].
AB  - Acid-base balance was studied in 60 ulcer patients in exacerbation and after
      treatment with losek and blockers of H2-histamine receptors. In exacerbation, all
      the patients had acidosis of metabolic or respiratory type. Losek changed blood
      pH insignificantly, and one acidosis type changed for the other. A single
      ranitidin dose shifted pH to alkalosis in healthy subjects while ulcer patients
      given famotidine restored acid-base balance. The latter is shown to correlate
      with gastric secretion of bicarbonates. Acidosis may contribute to exacerbation
      of ulcer.

PMID- 10881507
TI  - [On clinical manifestations of rotavirus-related gastroenteritis and possible
      links with its viral phoretype].
AB  - The results are presented of the study of rotavirus gastroenteritis course in 45
      patients (23 children and 22 adults) with different phoretypes. Phoretypical
      heterogeneity of rotavirus population was discovered among which the "long"
      phoretype prevailed. Rotavirus infection ran with diverse clinical symptoms:
      mild, moderate and severe. A lethal outcome occurred in an old male patient. No
      correlation was found between the phoretype and severity of the disease.

PMID- 10881508
TI  - [Antiphospholipid antibodies in Behcet's disease].
AB  - 35 patients with Behcet's disease (BD) were examined for antiphospholipid
      antibodies (aPL). Elevated levels of antibodies to cardiolipin (aCL) were
      registered in 20% of the patients (aCL IgG and IgM in 11.4 and 8.6%,
      respectively). Low positivity of these antibodies prevailed (33.2 GPL and 41.2
      MPL). Lupus anticoagulant was present in 6 patients. No distinct correlation was
      found between positivity by aPL and vascular disorders. It is inferred that aPL
      do not seem to play a leading role in thrombotic diathesis in BD. This diathesis
      is brought by a much more complicated and multifactor process.

PMID- 10881509
TI  - [New domestic phospholipid preparation "Fosfogliv" as an effective treatment for
      patients with acute viral hepatitis].
AB  - Patients with acute viral hepatitis B, A and mixed hepatitis B + C were treated
      in two independent clinics with phosphogliv--a new hepatoprotective drug based on
      polyunsaturated phosphatidylcholine and glycyrrhizic acid salt. Phosphogliv
      removed some symptoms of intoxication (nausea, weakness, jaundice, etc.) quicker
      than basic therapy. Among biochemical hepatitis markers, serum bilirubin level
      was most responsive to phosphogliv. Standard therapy decreases bilirubin by 30%
      on the average for 5 days, phosphogliv reduces bilirubin for one more week to
      half those values observed in control patients. At that point low
      aminotransferase activities were seen in phosphogliv treated patients. No side
      effects were seen. The new hepatoprotector phosphogliv which repairs biomembranes
      represents drugs of new generation compared to phospholipid drug essential.

PMID- 10881510
TI  - [Treatment of complicated forms of diabetic foot syndrome in the specialized
      surgical department].

PMID- 10881512
TI  - [Septic lesions in lungs of drug addicts].

PMID- 10881511
TI  - [Basic methods of treatment of and individual programs for patients with systemic
      lupus erythematosus].

PMID- 10881513
TI  - [Encephalitis combined with advanced vasculitis in a HIV infected woman].

PMID- 10881515
TI  - [Lethality in myocardial infarction].

PMID- 10881514
TI  - [Cholangiocarcinoma causing Badd-Chiari syndrome].

PMID- 10881516
TI  - [Circumcision of boys. A new law proposal will protect young boys against abuse].

PMID- 10881518
TI  - [Changing principles for respirator treatment. Is low tidal volume life-saving?].

PMID- 10881517
TI  - [Treatment of primary biliary cirrhosis. The effect of ursodeoxycholic acid is
      questioned now].

PMID- 10881519
TI  - [Circumcision of boys--a child's right versus parents' right].
AB  - Male circumcision was practiced long before Abraham established a covenant with
      God to the effect that he should circumcize himself and all male members of his
      house. Thereafter it has become a potent religion-ethnic commandment also in the
      Islamic world, although it is not mentioned in the Koran. Several million boys
      are circumcised yearly in for instance traditional Africa and the USA (in the USA
      originally as prophylaxis against masturbation). In Sweden the yearly figure is
      some 3000 boys. A comprehensive review of the literature reveals that there are
      no or only marginal medical benefits of the operation, particularly in view of
      the fact that up to 10% suffer complications, and also that newborns both
      experience pain and will respond more strongly to new pain stimuli for years to
      come. There are two opposing interests--those related to the religious tradition
      and those related to the welfare of the child as expressed in the United Nations
      Convention on the Rights of the Child.

PMID- 10881520
TI  - [Drug-induced enterocolitis. Important differential diagnosis in the
      investigation of diarrhea and intestinal hemorrhage].
AB  - This article is a review of the side-effects of drugs affecting the small and
      large intestines. Pseudomembranous colitis is caused by antibiotics facilitating
      an overgrowth of Clostridium difficile. A hemorrhagic colitis, generally self
      limiting, can be caused by penicillin, amoxycillin and ampicillin. Toxicity of
      NSAID may induce intestinal ulcers, diaphragm-like strictures, perforation,
      colitis and relapse of inflammatory bowel disease. Drug-induced lymphocytic
      colitis has been reported due to ticlopidine, Cyclo 3 Fort, and occasionally by
      ranitidine, carbamazepine, vinburnine, tardyferon, and flutamide. Sulphasalazine
      and 5-ASA can cause relapse of ulcerative colitis. Neutropenic enterocolitis is a
      severe complication to cytotoxic therapy for cancer. Ischemic colitis can be
      caused by drugs inducing mesenteric vasoconstriction.

PMID- 10881521
TI  - [The condition--not the drug--is decisive when it comes to subsidizing. Increased
      objectivity in the debate on subsidized "quality of life drugs" is required].

PMID- 10881522
TI  - [Viagra is first choice preparation in the treatment of erectile dysfunction.
      Access to a variety of methods makes individual treatment possible].
AB  - Several pharmacological treatments for erectile dysfunction (ED) have recently
      been introduced. This study performed during 1999 shows that in Sweden mostly men
      in their 60's, often with circulatory disease and/or diabetes, where the ones who
      were treated for ED. The most frequently used drug (80%) is sildenafil (Viagra).
      The mean consumption is 4.8 tablets per month, the same consumption as for
      intracavernous prostaglandin injections. The pattern of prescription doesn't
      differ between general practitioners and urological surgeons. No evidence for
      "overconsumption" became evident in the study. Presently, the majority of men who
      seek help for ED are middle-aged, have circulatory disease and are prescribed
      sildenafil (Viagra).

PMID- 10881523
TI  - [Fibromyalgia--a new name of an old "malady". Fatigue and pain syndrome with a
      historical background].
AB  - Fibromyalgia is a good illustration of the fact that a smart new name of an old
      malady can spread like wildfire if well matched in time socioculturally.
      "Muscular rheumatism" has earlier been looked upon as a (rheumatic) inflammation
      of muscle cells or of muscular connective tissue. During the last decades the
      interest of leading clinicians and researchers have been directed against the
      pain perceiving system, suggesting defect pain modulating mechanisms peripherally
      and centrally. Fibromyalgia seems to supply several medical and social needs in
      our time and might be called a "fin-de-siecle" disease.

PMID- 10881524
TI  - [Continuing medical education--increasing demands concerning the life-long
      learning].

PMID- 10881525
TI  - [Hyperhidrosis or withdrawal symptoms behind the Bounty mutiny?].

PMID- 10881526
TI  - [A moment in medicine, part 8. Just enough of closeness--the balance between
      closeness and distance].

PMID- 10881527
TI  - [Ritual circumcision of boys--an intervention against the UN convention].

PMID- 10881528
TI  - [Fibromyalgia--probably a result of prolonged stress syndrome].

PMID- 10881529
TI  - [Can weight reduction interventions help in obesity? Studies show increased
      morbidity after weight loss].

PMID- 10881530
TI  - [A comment: the core question for obese persons is quality of life. The Malmo
      study should not result in therapeutic nihilism].

PMID- 10881531
TI  - [The aqueous humor water mirror of the soul--on aqueous humor water dynamics].

PMID- 10881532
TI  - [Use available knowledge--also when it is not complete. Current example: chronic
      fatigue syndrome, fibromyalgia].

PMID- 10881533
TI  - [Computerized medical record--a potential quality instrument].

PMID- 10881534
TI  - [Visual fields and driver's licence].

PMID- 10881535
TI  - [A dilemma in health care--dental cleaning of heavy metals].

PMID- 10881536
TI  - [Dynamics of morbidity among liquidators of Chernobyl nuclear power station
      accident].
AB  - The article represents data on distribution of liquidators in Russian State
      Medical Dosimetry Register according to account categories, residing territories
      (regions of Russia), age, sex, dose groups, coverage by medical examinations and
      health groups. During 1991-1996 the liquidators demonstrated higher occurrence of
      endocrine, neurologic and sensory, circulatory, digestive and malignant diseases.

PMID- 10881537
TI  - [Changes of neurocytes in CNS under general exposure to UHF field with local
      protection applied].
AB  - Experiments on white rats were performed to study influence of UHF field on
      cortical sensomotor area under general exposure or with the head shielded. The
      changes in CNS caused by UHF field were not prevented completely by means of the
      shield. That is probably due to pathologic reflex impulses from the body
      receptors.

PMID- 10881538
TI  - [Changes in gastric electric activity and serum catecholamine level under the
      influence of electromagnetic microwaves (experimental studies)].
AB  - Chronic experiments on 17 dogs revealed that ultrahigh-frequency electromagnetic
      waves applied on epigastric area and head induce a double-phase response:
      depressed electric activity of gaster and increased total catecholamines level
      during exposure, but higher gastric activity and lower levels of epinephrine and
      norepinephrine in 24 hours after each of 10 procedures and during 7 days after 10
      procedures. Double-phase changes in electric activity of gaster could be
      explained by double-phase fluctuations of humoral division in chromaffin system.

PMID- 10881539
TI  - [Specifics of medical and social examination for permanent disability in
      occupational sensorineural hearing loss].
AB  - Based on analysis of occupational examination results for patients with
      occupational neuro-sensory deafness, the authors necessitate unification of
      approaches to elaboration of work recommendations considering degree of deafness
      due to occupational noise and other hazards, because these recommendations serve
      as a basis for occupational experts to estimate degree of persistent disablement.

PMID- 10881540
TI  - [Orthostatic work factor and its place in classification of work hardness].
AB  - The authors suggest percentage of work time in orthostatic posture as a basic
      indicator of orthostatic work factor. This indicator correlates with prevalence
      of varicose disease and is recommended for evaluation of work hardiness in units.
      The diagram presented characterizes a paradigm and serves as a point for
      quantitative evaluation of work hardiness in orthostatic posture.

PMID- 10881541
TI  - [Quantitative evaluation of pilot workload influence on functional stability and
      occupational health of pilots (scientific and practical aspects)].
AB  - Based on early concepts of quantitative evaluation of pilotage overload influence
      on pilot, the authors justified principles and criteria for biometric
      characterization of overload parameters and human response concerning the problem
      of manoeuvreable flight and pilot's occupational health preservation. The article
      presents quantitative dependencies between various overload parameters,
      occupational conditions and -effects, considering risk of disorders that
      determine potential unreliability of pilot in manoeuvreable flight and possible
      cumulative effects from dose viewpoint.

PMID- 10881542
TI  - [Relevance of psychophysiological occupational selection of sailors (review of
      literature)].

PMID- 10881543
TI  - [The evaluation of the consequences of electromagnetic irradiation of hands in
      operators of high-frequency welding devices].
AB  - Method of secondary sources (method of integral equations) was applied to
      calculate specific absorbed intensity in hands of operators working at non
      shielded high-frequency (27.12 Mhz) welding devices. The authors present
      calculations for "female" and "male" hand sizes, give recommendations on lower
      level of specific absorption.

PMID- 10881544
TI  - [Register of persons having occupational diseases caused by work with sources of
      ionizing radiation].
AB  - The authors present methodic approaches to elaboration of a Special Register of
      individuals engaged into nuclear power industry and having occupational diseases
      caused by work with sources of ionizing radiation. The article deals with input
      and output documents, methods of input information control, technologic scheme of
      the Register functioning and stages of its pilot exploitation.

PMID- 10881545
TI  - [Electromagnetic environment in living and office facilities].

PMID- 10881546
TI  - [Mineral density of bones and parameters of phosphorus-calcium metabolism in
      workers of chlorine-organic synthesis].

PMID- 10881548
TI  - [In Process Citation]

PMID- 10881547
TI  - [Age characteristics of motor activities of violinists' hands].

PMID- 10881549
TI  - Brain potentials associated with recollective processing of spoken words.
AB  - The neurocognitive foundations of recollection can be explored by recording event
      related potentials (ERPs) from the human brain. In the present study, we
      monitored brain activity while participants heard a series of words, first in a
      study phase and again, 1-2 min later, in a test phase, when both priming and
      recognition were measured. Level of processing at study was manipulated within
      subjects via instructions either to visualize the referent of each word (the
      image task) or to detect the presence of target letters (the letter task).
      Priming of lexical decision response time was observed but did not differ across
      study task, whereas recognition was better for image- than for letter-task words.
      Brain potentials recorded at test revealed a task effect, wherein ERPs were more
      positive for image- than for letter-task words approximately 600-900 msec after
      word onset. The task effect was restricted to posterior scalp locations and was
      interpreted as an indication of visual imagery triggered by spoken words. Given
      that similar potentials were also elicited at study, we speculate that accurate
      recognition of words from the image task involved the recapitulation of the
      visual imagery that was initially engaged during the study phase.

PMID- 10881550
TI  - Cognitive inhibition in selection and sequential retrieval.
AB  - Inhibitory models of working memory efficiency (Engle, 1996; Zacks & Hasher,
      1994) assert that individual differences in working memory reflect the efficiency
      of inhibitory processes that exclude irrelevant information and suppress no
      longer-relevant information. The present study examined the implication that
      these two inhibitory processes operate at consistent levels of efficiency within
      individuals by examining the correlation between two cognitive inhibition
      effects, negative priming and negative error priming. Negative priming involves
      slower response to a probe-trial target that was used as a to-be-ignored
      distractor on the immediately preceding prime trial. Negative error priming is
      the phenomenon that errors in a sequence of simple arithmetic trials are unlikely
      to involve the correct answer to the preceding problem. Participants received
      distractor-target pairs of simple addition problems and were required to produce
      the target problem sum. Negative priming was observed for prime distractors,
      whereas negative error priming was observed in connection with previous targets
      but not distractors. Consistent with the assumptions of these working memory
      models, the magnitudes of the two effects were significantly correlated.

PMID- 10881551
TI  - On the interpretation of working memory span in adults.
AB  - Experimental research into children's working memory span has shown that
      retention duration contributes substantially to span performance, while
      processing efficiency need not be related to concurrent memory load (Towse,
      Hitch, & Hutton, 1998). These findings have been used to argue for a model of
      working memory span that emphasizes time-based forgetting rather than the popular
      resource-sharing or tradeoff framework. The present paper considers whether
      adults perform working memory span tasks in a qualitatively different way. Data
      from reading span and operation span tasks show that adults' performance can be
      distinguished from that of children, but also that a task-switching model of
      working memory span can explain some important aspects of performance.

PMID- 10881552
TI  - The role of phonology in a letter detection task.
AB  - In two experiments, we investigated whether onsets and rimes have a role in the
      processing of written English. In both experiments, participants detected letter
      targets (e.g., t) in nonwords like vult faster than in nonwords like vust. This
      finding is consistent with Selkirk's (1982) view that sonorants (e.g., the /l/ of
      vult) cohere with preceding short vowels and are part of the vowel nucleus. In
      contrast, the /t/ of vust is part of the syllable's coda st and so is harder to
      isolate. Experiment 2 demonstrated that the time required for one to detect
      single-member codas following vowel digraphs (e.g., the t in veet) was similar to
      the time to detect the same target letter following a postvocalic sonorant (e.g.,
      the t in vult). No evidence was found for onsets. The results provide support for
      a phonological organization among letters of printed rimes.

PMID- 10881553
TI  - The odd-even effect in multiplication: parity rule or familiarity with even
      numbers?
AB  - This study questions the evidence that a parity rule is used during the
      verification of multiplication. Previous studies reported that products are
      rejected faster when they violate the expected parity, which was attributed to
      the use of a rule (Krueger, 1986; Lemaire & Fayol, 1995). This experiment tested
      an alternative explanation of this effect: the familiarity hypothesis. Fifty
      subjects participated in a verification task with contrasting types of problems
      (even x even, odd x odd, mixed). Some aspects of our results constitute evidence
      against the use of the parity rule: False even answers were rejected slowly, even
      when the two operands were odd. We suggest that the odd-even effect in
      verification of multiplication could not be due to the use of the parity rule,
      but rather to a familiarity with even numbers (three quarters of products are
      indeed even).

PMID- 10881554
TI  - Implicit motor sequence learning is represented in response locations.
AB  - Previous work (Willingham, 1999) has indicated that implicit motor sequence
      learning is not primarily perceptual; that is, what is learned is not a sequence
      of stimuli. Still other work has indicated that implicit motor sequence learning
      is not specific to particular muscle groups or effectors. In the present work, we
      tested whether implicit motor sequence learning would be represented as a
      sequence of response locations. In Experiment 1, learning showed very poor
      transfer when the response locations were changed, even though the stimulus
      positions were unchanged. In Experiment 2, participants switched their hand
      positions at transfer, so that one group of participants pushed the same sequence
      of keys but used a different sequence of finger movements to do so, whereas
      another group pushed a different sequence of keys but used the same sequence of
      finger movements used at training. Knowledge of the sequence was shown at
      transfer only if the sequence of response locations was maintained, not the
      sequence of finger movements.

PMID- 10881555
TI  - Constraints on using the dual-task methodology to specify the degree of central
      executive involvement in cognitive tasks.
AB  - The dual-task paradigm has been used to examine the role of the central executive
      in various cognitive tasks. In these studies, performance decrements in primary
      cognitive tasks performed concurrently with secondary executive tasks have been
      interpreted as evidence for the involvement of the central executive in those
      primary tasks. In the present study, we examined the effects of different
      secondary tasks on performance of three psychometric visuospatial tasks. The
      decrement in performance of these tasks when they were paired with secondary
      executive tasks was smallest for the psychometric task considered to most heavily
      involve the central executive and largest for the task considered least demanding
      of executive mechanisms. We propose that, when applied to the assessment of
      central executive involvement, the prevalent simple dual-task logic does not
      always apply. Special conditions that limit the application of the dual-task
      methodology include two inherently related factors--a response selection
      bottleneck and a strategic tradeoff between primary and secondary tasks.

PMID- 10881556
TI  - Category structure and created memories.
AB  - Cued recall of categorized lists was used to examine effects of category
      structure on the creation of false memories. In three experiments, category
      members that had not been presented on studied categorized lists were nonetheless
      recalled by participants. Delaying the category cued recall test (Experiment 1)
      and priming category members that had been omitted from target lists (Experiment
      3) increased the frequency of false recall. All three experiments showed that
      nonpresented category members that were higher in output dominance were more
      frequent intrusions. The typicality of category members, however, did not
      uniquely contribute to the predictability of false recall (or accurate recall)
      once the contribution of output dominance was taken into account, suggesting that
      item accessibility (related to output dominance) may be more instrumental than
      item distinctiveness (related to typicality) in causing certain types of false
      recall. The results show that created memories in category cued recall are
      strongly biased by prior category knowledge and can be predicted by the graded
      structure of categories, particularly in terms of the output dominance of
      category instances.

PMID- 10881557
TI  - Perspective effects in nondeontic versions of the Wason selection task.
AB  - Perspective effects in the Wason four-card selection task occur when people
      choose mutually exclusive sets of cards depending on the perspective they adopt
      when making their choice. Previous demonstrations of perspective effects have
      been limited to deontic contexts--that is, problem contexts that involve social
      duty, like permissions and obligations. In three experiments, we demonstrate
      perspective effects in nondeontic contexts, including a context much like the
      original one employed by Wason (1966, 1968). We suggest that perspective effects
      arise whenever the task uses a rule that can be interpreted biconditionally and
      different perspectives elicit different counterexamples that match the predicted
      choice sets. This view is consistent with domain-general theories but not with
      domain-specific theories of deontic reasoning--for example, pragmatic reasoning
      schemas and social contract theory--that cannot explain perspective effects in
      nondeontic contexts.

PMID- 10881558
TI  - The modality-specific and -nonspecific components of long-term priming are
      frequency sensitive.
AB  - Five experiments were carried out to test the claim that the modality-specific
      and modality-nonspecific components of long-term priming are differentially
      sensitive to word frequency, with the specific component being less affected. In
      contrast with this claim, specific and nonspecific priming were similarly reduced
      for high-frequency words in three lexical decision and two perceptual
      identification experiments. These findings highlight the important role of
      frequency in modulating priming as well as provide a basic constraint for future
      theories of priming. In addition, the roles of task and student population in
      modulating priming are examined.

PMID- 10881559
TI  - Causal judgment from contingency information: relation between subjective reports
      and individual tendencies in judgment.
AB  - In two experiments, participants made causal judgments from contingency
      information for problems with different objective contingencies. After the
      judgment task, the participants reported how their judgments had changed
      following each type of contingency information. Some reported idiosyncratic
      tendencies--in other words, tendencies contrary to those expected under
      associative-learning and normative rule induction models of contingency judgment.
      These idiosyncratic reports tended to be better predictors of the judgments of
      those who made them than did the models. The results are consistent with the view
      that causal judgment from contingency information is made, at least in part, by
      deliberative use of acquired and sometimes idiosyncratic notions of evidential
      value, the outcomes of which tend, in aggregate, to be highly correlated with the
      outcomes of normative procedures.

PMID- 10881560
TI  - Effects of antecedent order and semantic context on Chinese pronoun resolution.
AB  - Three reading time experiments were conducted in order to examine the relative
      contributions of order of antecedents and semantic context to the resolution of
      temporarily ambiguous Chinese pronouns. These pronouns were ambiguous because
      each of them was preceded by two antecedents, both of which were likely
      candidates for coreference. The identity of the pronoun was revealed by
      subsequent disambiguating information that constrained the pronoun to one
      particular interpretation. Experiment 1 showed that reading of the disambiguating
      phrase was slower when the phrase confined the pronoun to the second rather than
      to the first antecedent. Experiment 2 produced the same effect of antecedent
      order (first vs. second antecedent) regardless of whether the target antecedent
      was an action-performing or an action-receiving entity. In Experiment 3, the
      order effect was eliminated by a biasing modifier inserted immediately before the
      pronoun. These results indicate that in a semantically neutral environment, the
      first-appearing antecedent is the preferred candidate for coreferencing the
      ambiguous Chinese pronoun. The interaction between order of antecedents and
      semantic context (in the form of preposed biasing modifiers) suggests that the
      initial comprehension of Chinese pronouns depends as much on contextual as on
      structural factors.

PMID- 10881561
TI  - Concept learning and feature interpretation.
AB  - Models of categorization often assume that people classify new instances directly
      on the basis of the presented, observable features. Recent research, however, has
      suggested that the coherence of a category may depend in part on more abstract
      features that can link together observable features that might otherwise seem to
      have little similarity. Thus, category learning may also involve the
      determination of the appropriate abstract features that underlie a category and
      link together the observable features. We show in four experiments that
      observable features of a category member are often interpreted as congruent with
      abstract features that are suggested by observable features of other highly
      available category members. Our discussion focuses on the implications of these
      findings for future research.

PMID- 10881562
TI  - Illusions in quantified reasoning: how to make the impossible seem possible, and
      vice versa.
AB  - The mental model theory postulates that reasoners build models of the situations
      described in premises, and that these models normally represent only what is
      true. The theory has an unexpected consequence. It predicts the existence of
      illusions in inferences. Certain inferences should have compelling but erroneous
      conclusions. Two experiments corroborated the occurrence of such illusions in
      inferences about what is possible from disjunctions of quantified assertions,
      such as, "at least some of the plastic beads are not red." Experiment 1 showed
      that participants erroneously inferred that impossible situations were possible,
      and that possible situations were impossible, but that they performed well with
      control problems based on the same premises. Experiment 2 corroborated these
      findings in inferences from assertions based on dyadic relations, such as, "all
      the boys played with the girls."

PMID- 10881563
TI  - Asymptotic judgment of cause in a relative validity paradigm.
AB  - We report three experiments in which we tested asymptotic and dynamic predictions
      of the Rescorla-Wagner (R-W) model and the asymptotic predictions of Cheng's
      probabilistic contrast model (PCM) concerning judgments of causality when there
      are two possible causal candidates. We used a paradigm in which the presence of a
      causal candidate that is highly correlated with an effect influences judgments of
      a second, moderately correlated or uncorrelated cause. In Experiment 1, which
      involved a moderate outcome density, judgments of a moderately positive cause
      were attenuated when it was paired with either a perfect positive or perfect
      negative cause. This attenuation was robust over a large set of trials but was
      greater when the strong predictor was positive. In Experiment 2, in which there
      was a low overall density of outcomes, judgments of a moderately correlated
      positive cause were elevated when this cause was paired with a perfect negative
      causal candidate. This elevation was also quite robust over a large set of
      trials. In Experiment 3, estimates of the strength of a causal candidate that was
      uncorrelated with the outcome were reduced when it was paired with a perfect
      cause. The predictions of three theoretical models of causal judgments are
      considered. Both the R-W model and Cheng's PCM accounted for some but not all
      aspects of the data. Pearce's model of stimulus generalization accounts for a
      greater proportion of the data.

PMID- 10881564
TI  - The use of schematic knowledge about sources in source monitoring.
AB  - Source monitoring refers to mental processes leading to attributions regarding
      the origin of information. We tested Johnson, Hashtroudi, and Lindsay's (1993)
      assumption that prior source-relevant knowledge is used in some source-monitoring
      tasks. In two experiments using different domains of schematic knowledge, two
      sources presented information that was expected for one source and somewhat
      unexpected for the other. In a later source-monitoring test, participants decided
      whether items had been presented by Source A, by Source B, or were new. The
      results of both experiments show that source identification is better for
      expected items than for somewhat unexpected items. Multinomial modeling analyses
      revealed that when participants do not remember the source of information, they
      guess that it was presented by the expected source. These results provide
      evidence for the claim that source monitoring can be based on prior knowledge and
      support a guessing hypothesis.

PMID- 10881565
TI  - Whiplash backlash.

PMID- 10881566
TI  - Muscles can be a pain in the neck.

PMID- 10881567
TI  - At the heart of the matter.

PMID- 10881568
TI  - Major league dreams.

PMID- 10881569
TI  - Child's play? Kids, sports, and injury.

PMID- 10881570
TI  - Mastering the medicine of motion.

PMID- 10881571
TI  - Physicians may receive more questions about asbestos-related disease.

PMID- 10881572
TI  - Children are dying for some exercise.

PMID- 10881573
TI  - Pharmacotherapy in ADHD. Guidelines for prescribing stimulant medications in
      young children.

PMID- 10881574
TI  - Preventing upper extremity overuse injuries in child and adolescent athletes.
AB  - Physicians who treat young athletes must not only correctly diagnose specific
      musculoskeletal injuries but also pay attention to factors that predispose the
      patient to the injury. This article reviews the intrinsic and extrinsic factors
      that can lead to upper extremity overuse injury in child and adolescent athletes
      and describes the physician's role in preventing injury in this population.

PMID- 10881575
TI  - Diagnosing and treating ADHD in children.
AB  - In the absence of a definitive diagnostic test for attention
      deficit/hyperactivity disorder, physicians should use the DSM-IV, various
      standardized assessment instruments, and data from parents, teachers, and others
      to guide them in making an accurate assessment of children suspected of having
      the disorder. Treatment frequently includes drugs and behavioral therapies, with
      positive results.

PMID- 10881576
TI  - Diagnosing childhood attention-deficit/hyperactivity disorder. Do family
      practitioners and pediatricians make the same call?
AB  - BACKGROUND: The purpose of this study was to determine whether--and if so, how-
      primary care physicians in Minnesota differ in diagnosing and treating childhood
      ADHD. METHODS: A questionnaire was mailed to 200 family physicians (100 urban;
      100 rural) and 100 pediatricians (60 urban; 40 rural). The questionnaire asked
      about assessment, diagnosis, and treatment strategies physicians would use in
      response to three patient vignettes. RESULTS: While all physicians in both
      specialities reported similar differential diagnoses, pediatricians used more
      special tests and assessment scales than family physicians (p < 0.05). More
      family physicians referred patients for further evaluation (p < 0.05). Eighty
      nine percent of pediatricians used DSM-IV criteria compared with 37% of family
      physicians (p < 0.001). Parents (98%) and teachers (82%) were usually involved in
      management planning, and methylphenidate (Ritalin) was the most commonly
      prescribed drug (87%). CONCLUSION: Regardless of specialty, size of community, or
      distance from mental health services, physicians in this study did not differ in
      the diagnosis or treatment of ADHD in response to hypothetical cases.
      Pediatricians reported using DSM-IV criteria in their practices when making
      diagnoses more often than family physicians.

PMID- 10881577
TI  - Recent increase in the frequency of infant measles in Japan.
AB  - BACKGROUND: Because there has been no major outbreak of measles in Japan during
      the last decade, subclinical boosting of pre-existing immunity by exposure to
      epidemic measles is unlikely to have occurred. Consequently, the measles immunity
      of mothers of this generation is less well developed and they provide less
      effective passive immunity to their infants. An increase in the frequency of
      infant measles is therefore probable. METHOD AND RESULTS: A retrospective review
      was undertaken of the clinical records of all measles cases that occurred in the
      last 3 years in eight hospitals and two out-patient clinics in Hokkaido. Of 541
      recorded cases, 96 (17.7%) were infants and of these, 66 patients (68.8%) were
      over 9 months of age. Only 20 children had received measles vaccination.
      CONCLUSION: There has been a recent increase in the frequency of infant measles,
      suggesting an increased population of infants susceptible to measles before the
      age of 1. Of the older patients, 95% had not been vaccinated against measles.
      Increasing the rate of measles vaccination may help suppress future measles
      outbreaks and assist in protecting infants until they pass their first birthday.

PMID- 10881578
TI  - Methylenetetrahydrofolate reductase polymorphism in Kawasaki disease.
AB  - BACKGROUND: A genetic aberration in the 5,10-methylenetetrahydrofolate reductase
      (MTHFR) gene (677 C to T substitution) has been shown to result in reduced enzyme
      activity. The hypothesis tested in the present study was that a higher proportion
      of Kawasaki disease (KD) patients with coronary artery lesions (CAL) would have
      the T677 allele compared with patients without CAL and healthy subjects. METHODS:
      Genotypes for MTHFR were determined in 75 KD patients (male:female ratio 52:23)
      and 238 healthy subjects (male:female ratio, 110:128) by the polymerase chain
      reaction and restriction fragment length polymorphism method. RESULTS: The
      results indicated that female KD patients had a significantly higher frequency of
      the TT genotype compared with female control subjects. In the female population,
      the frequency of the TT genotype in patients with initial coronary aneurysm was
      significantly lower than in patients without this manifestation. Analysis of the
      data for the male population showed that the frequency of the TT genotype in KD
      patients developing coronary stenosis, occlusion or myocardial infarction was
      higher than that in those without these manifestations, although the difference
      was statistically insignificant. CONCLUSIONS: The TT genotype may protect female
      KD patients against initial aneurysm formation and predispose male KD patients to
      severe coronary complications. Further large-scale studies may be required to
      confirm the contribution of homocysteine in the coronary sequelae of KD.

PMID- 10881580
TI  - Nitric oxide-related compounds in patients with congenital heart defects and
      pulmonary hypertension.
AB  - BACKGROUND: The relationship between blood levels of nitric oxide (NO)-related
      compounds in patients with congenital heart defects (CHD) and degree of pulmonary
      hypertension (PH) has not yet been described. METHODS: Thirty-six patients (aged
      6 months to 19 years) with CHD were divided into three groups on the basis of
      their hemodynamic characteristics: group 1 (control, n = 5), left-to-right shunt
      (-) without PH (pulmonary to systemic artery peak pressure ratio, Pp/Ps < 0.4);
      group 2 (n = 14), left-to-right shunt (+) without PH; group 3 (n = 17), left-to
      right shunt (+) with PH (Pp/Ps > 0.4). Blood samples were obtained from the right
      atrium, pulmonary artery, left atrium or pulmonary capillary wedge and aorta
      during cardiac catheterization. All NO-related compounds in whole blood were
      measured by chemiluminescent assay using Sievers NO analyzer. RESULTS: The
      sampling site had no significant impact on NO-related compound levels. However,
      the patients with PH (group 3) had significantly higher (P < 0.01) blood levels
      of NO-related compounds (117.3 +/- 14.7 mumol/L) than the patients without PH
      (groups 1 and 2, 23.9 +/- 3.2 and 38.4 +/- 4.8 mumol/L, respectively). In
      addition, pulmonary artery resistance (Rp) values of less than 6 Wood U/m2 were
      directly correlated with levels of NO-related compounds, whereas Rp values
      greater than 6 Wood U/m2 were inversely correlated with blood levels of NO
      related compounds. CONCLUSION: The present results suggest that the hemodynamic
      status of the pulmonary circulation in CHD affects, at least partly, blood levels
      of NO-related compounds.

PMID- 10881579
TI  - Plasma brain natriuretic peptide concentrations in patients with Kawasaki
      disease.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) is a cardiac hormone and plasma
      levels of it increase in patients with congestive heart failure and in those with
      acute myocardial infarction. Kawasaki disease (KD) is a well-known generalized
      vasculitis and the most prominent features of this disease are the cardiovascular
      manifestations, which involve the pericardium, myocardium, endocardium and
      coronary arteries. It was hypothesized that the plasma concentrations of BNP in
      patients with KD might be increased and that plasma BNP might be a useful
      biological marker of cardiovascular manifestations in patients with KD. METHODS:
      Blood was obtained to measure and compare plasma BNP concentrations in the acute
      (n = 32) and convalescent (n = 35) phases of KD and in the acute phase of the
      patients with viral infection (n = 26), which included adenovirus, influenza,
      measles and herpes group virus infection. In patients with KD, two-dimensional
      echocardiography was performed to check for pericardial effusion and coronary
      arterial lesions and to measure the dimensions of the left ventricle at diastole
      and the shortening fraction of the left ventricle (LVSF). RESULTS: The mean
      plasma BNP concentration in patients with KD in the acute phase was 55.0 +/- 39.5
      pg/mL, but was 6.8 +/- 7.3 pg/mL in patients with viral infection. The plasma BNP
      concentration in patients with KD in the acute phase was significantly higher
      than in patients with viral infection (P < 0.0001). In 31 cases of KD, the plasma
      BNP concentrations were measured both in the acute and convalescent phases. The
      mean plasma BNP concentration in the acute phase of KD was 55.3 +/- 40.1 pg/mL
      and in the convalescent phase was 5.9 +/- 5.7 pg/mL. The level of plasma BNP
      decreased significantly in the convalescent phase (P < 0.0001). The mean BNP
      level in patients with KD with pericardial effusion (n = 8) in the acute phase
      was 80.3 +/- 43.4 pg/mL and that in patients without pericardial effusion (n =
      24) was 46.5 +/- 35.1 pg/mL. The BNP level in patients with pericardial effusion
      was significantly higher than that of patients without pericardial effusion (P <
      0.05). There was no significant correlation between the plasma concentrations of
      BNP in the acute phase of KD and LVSF (r = -0.161, P = 0.39, n = 31). CONCLUSION:
      It was shown that the plasma BNP concentration increased in the acute phase of KD
      and decreased to within normal range in the convalescent phase. Further
      examinations are needed to clarify the mechanism by which the elevated levels of
      plasma BNP occur in the acute phase of KD. However, plasma BNP might be a useful
      biological marker of the cardiovascular manifestations in patients with KD.

PMID- 10881581
TI  - Inhalation of nebulized nitroglycerin in dogs with experimental pulmonary
      hypertension induced by U46619.
AB  - BACKGROUND: Pulmonary hypertension (PH) causes mortality in some congenital and
      acquired heart and lung diseases. However, inhalation of NO gas requires
      complicated and expensive instruments and elaborate preparations to avoid toxic
      gas administration. We tested the effectiveness and safety of inhaled nebulized
      nitroglycerin (Neb-NTG) in dogs with experimental PH. METHODS: Experimental PH
      was induced by continuous infusion of a thromboxane analog (U46619). The U46619
      infusion rate was adjusted to maintain a systolic pulmonary artery pressure (PAP)
      at 40 mmHg in 10 anesthetized and mechanically ventilated dogs. Then, 20
      micrograms/kg of NTG liquid nebulized by compressed air was inhaled. RESULTS:
      After infusion of U46619, the systolic, diastolic and mean PAP increased by 119%,
      228% and 169%, respectively, and the systolic, diastolic and mean systemic
      arterial pressures (SAP) increased by 19%, 29% and 23%, respectively. The
      systolic pulmonary to systemic pressure ratio (Pp/Ps) and mean Pp/Ps increased by
      83% and 113%, respectively, and the pulmonary vascular resistance (PVR), systemic
      vascular resistance (SVR) and pulmonary to systemic resistance ratio (Rp/Rs)
      increased by 341%, 100% and 145%, respectively. After inhalation of Neb-NTG in
      dogs with experimental PH, systolic, diastolic and mean PAP and PVR decreased by
      25 +/- 4, 26 +/- 11, 25 +/- 9 and 31 +/- 21%, respectively. There were no
      significant changes in systolic, diastolic and mean SAP, SVR, cardiac output and
      plasma methemoglobin concentrations. The systolic and mean Pp/Ps decreased by 18
      +/- 7 and 20 +/- 7%, respectively. The Rp/Rs decreased by 25 +/- 13%.
      CONCLUSIONS: The results of this study demonstrate that Neb-NTG is an effective
      and selective pulmonary vasodilator and may offer a new therapeutic option for
      PH.

PMID- 10881582
TI  - Coronary risk factors in Turkish schoolchildren: randomized cross-sectional
      study.
AB  - BACKGROUND: There is a strong association between the extent of atherosclerotic
      lesions in aorta and coronary arteries and antemortem risk factors in children
      and young adults. Cardiovascular diseases are the most common cause of death in
      adults in Turkey. However, the data about the extent of coronary risk factors in
      Turkish children is very limited. The aim of this cross-sectional study was to
      investigate the prevalence of coronary risk factors in Turkish schoolchildren
      living in Eskisehir, Turkey. METHODS: A randomly selected population of 4026
      schoolchildren, aged between 7 and 18 years, residing in urban and rural parts of
      Eskisehir were evaluated for coronary risk factors, using previously predicted
      risk threshold values. RESULTS: Hypertension was found in 4.8% of the girls and
      3.8% of the boys, 14.9% of the girls and 10.8% of the boys had abnormal lipid
      values, 18.2% of the girls and 26.4% of the boys had elevated total body fat
      percentages, 20.7% of the girls and 14.5% of the boys had physical inactivity and
      3.8% of the girls and 11.4% of the boys were regular smokers. Urban children had
      higher rates of hypercholesterolemia; however, rural children had higher rates of
      physical inactivity. When the modifiable risk factors were considered, excluding
      family history, 47.7% of the children had at least one risk factor and 11.7% of
      them exhibited two or more risk factors. CONCLUSIONS: Turkish schoolchildren
      living in Eskisehir had considerably high levels of coronary risk factors. The
      interventional measures established in childhood, during which the lifestyle and
      habits responsible for coronary heart diseases are acquired, will be very
      effective for preventing and modifying the risk factors predisposing children to
      coronary heart disease.

PMID- 10881583
TI  - Pulmonary complications in patients with staphylococcal sepsis.
AB  - BACKGROUND: The aim of the present study was to determine the pulmonary findings
      in patients with sepsis caused by Staphylococcus aureus. METHODS: The clinical
      and laboratory findings of 32 cases (82%) of pulmonary involvement (secondary
      pneumonia) of 39 patients with sepsis caused by S. aureus were studied
      retrospectively. The criteria for the diagnosis of sepsis were clinical evidence
      of infection plus hyperthermia/hypothermia, tachycardia, tachypnea and white
      blood cell abnormalities. Secondary pneumonia was diagnosed in patients who
      presented with staphylococcal disease at one or more non-pulmonary sites and who
      developed radiologic evidence of pulmonary involvement during the course of
      illness. RESULTS: Of the 32 patients, 23 were male and nine were female; the male
      to female ratio was 2.5/1. The ages of the patients ranged from 2 months to 14
      years (7.87 +/- 4.71 years). Bronchopneumonic infiltration was bilateral in 18
      patients and unilateral in 14 patients (20 patients (62.5%) had lobar
      consolidation). Pleurisy was noted in 12 (37.5%) patients; it was on the right
      side in five patients, on the left in five patients and bilateral in two
      patients. In contrast, pneumatocele and pneumothorax were observed in seven
      (21.9%) and four (12.5%) patients, respectively. Closed chest tubes were placed
      through a closed thoracotomy in five children who developed dyspnea, orthopnea
      with imminent respiratory failure and mediastinal shift. As well as the pulmonary
      involvement, arthritis was noted in 13 patients, osteomyelitis in 11 patients,
      rash in six patients, pericarditis in five patients and renal failure in one
      patient. Staphylococcus aureus was isolated from blood culture in all except for
      seven cases. While S. aureus was isolated from blood culture in all of the 12
      patients with pleurisy, it was isolated from pleural fluid in only two (16.6%)
      patients. Six of 32 patients died; the mortality rate was 18.75%. CONCLUSIONS: It
      was found that the rate of pulmonary involvement was as high as 82% in sepsis
      caused by S. aureus, and the pulmonary findings, including bronchopneumonic
      infiltration and lobar consolidation, were frequently seen in S. aureus
      pneumonia, causing a mortality rate of 18.75%.

PMID- 10881584
TI  - Are high barometric pressure, low humidity and diurnal change of temperature
      related to the onset of asthmatic symptoms?
AB  - BACKGROUND: Meteorologic factors play a role in the expression of asthmatic
      symptoms; however, there are controversies about the causal relationship between
      meteorologic factors and asthma. The relationship between meteorologic parameters
      and emergency admissions for asthmatic symptoms in this hospital were analyzed.
      METHODS: A total of 205 patients (130 boys and 75 girls, 0.1-16.6 years of age)
      who were admitted to Hakodate Chuo General Hospital for asthmatic symptoms
      between 1 January and 31 December 1997 were submitted to our study. We divided a
      total of 365 days into two groups of days with and without any admissions.
      Meteorologic factors for the days with admissions and 1-3 days before
      hospitalization were compared with those of the days of no admissions.
      Statistical analysis was done with the Mann-Whitney U-test. RESULTS: On the days
      with admissions and 1 day before hospitalizations, barometric pressure was higher
      and relative humidity lower than on days with no admissions. The diurnal
      difference between maximum and minimum temperature for days 1 day before days
      with admissions was larger than that for 1 day before days with no admissions.
      CONCLUSIONS: It is thought that change in barometric pressure, relative humidity
      and temperature had some influence on the worsening of asthmatic symptoms.

PMID- 10881585
TI  - Herpes zoster in immunocompetent and immunocompromised Japanese children.
AB  - BACKGROUND: To confirm epidemiological features of herpes zoster among children
      with or without immunosuppression, herpes zoster patients who had presented to
      this hospital were retrospectively investigated. METHODS: Medical records were
      reviewed for the 92 cases of pediatric herpes zoster patients diagnosed during
      the period from 1981 to 1998. The age at onset of herpes zoster and of varicella,
      the interval between varicella and zoster, the dermatomal distribution of herpes
      zoster and complications were compared between immunocompetent and
      immunocompromised children. RESULTS: The mean age at onset of zoster in
      immunocompetent children was 8.5 +/- 4.0 years and in immunosuppressed children
      was 9.7 +/- 3.8 years. The age at onset of varicella was significantly lower (1.6
      +/- 1.8 years) in immunocompetent than in immunosuppressed children (4.6 +/- 2.7
      years). The interval between varicella and zoster was 6.2 +/- 3.2 years in
      immunocompetent children. More than 80% of patients with acute leukemia or
      malignant lymphoma had herpes zoster within 2 years after diagnosis of
      malignancy. Lesions of herpes zoster were most frequently found in the thoracic
      nerve regions. Five of 11 zoster patients with cutaneous dissemination, three of
      five zoster patients having aseptic meningitis and three of four patients
      complicated facial palsy were children without underlying disease. CONCLUSIONS:
      The present study confirmed that varicella in the first year of life was a risk
      factor in immunocompetent children, as reported previously. Herpes zoster in
      children without immunosuppression was found not to be as mild as generally
      accepted.

PMID- 10881586
TI  - Risk factors for nutritional rickets among children in Kuwait.
AB  - AIM: To assess the risk factors for nutritional rickets among children in Kuwait.
      METHODS: One hundred and three children with rickets and 102 control children
      matched for age and socioethnic characteristics were recruited over a 2 year
      period (January 1995 to January 1997) in Al-Adan Hospital in Kuwait. Diagnosis
      was made on clinical, radiologic and biochemical parameters. A specially designed
      questionnaire was administered by one of the investigators to both mothers of
      patients and mothers of control subjects to assess the role of social,
      nutritional and other related factors in the pathogenesis of nutritional rickets.
      Biochemical investigations included estimation of hemoglobin, serum calcium,
      serum phosphorus, serum alkaline phosphatase and serum 25-hydroxy vitamin D.
      RESULTS: The mean birthweights of rickets patients and control subjects were 3.20
      +/- 0.46 and 3.19 +/- 0.45 kg, respectively. At the time of diagnosis,
      bodyweights of the patients and controls were 9.36 +/- 1.50 and 10.15 +/- 2.10
      kg, respectively. Heights at the time of diagnosis were 73.58 and 77.24 cm for
      the patients and the controls, respectively. Mean hemoglobin, serum calcium and
      serum phosphate were significantly lower in the patients compared with the
      controls. Alkaline phosphatase was higher among the patients (P < 0.0001). The
      mean serum 25-hydroxy vitamin D level of the patients was 26.5 nmol/L, compared
      with 83.5 nmol/L in the controls. The mean age of starting semisolid feeds for
      the patients was 8.12 months, compared with 5.7 months in the controls. The
      nutritional quality of semisolid feeds was adequate among 71.6% of the controls
      as opposed to 13.6% of the patients. CONCLUSION: Nutritional rickets is a
      multifactorial condition. However, several factors seem to make important
      contributions. Among these, lack of exposure to sunlight, prolonged breast
      feeding without supplementation and inadequate weaning practices are important.
      Maternal education is important as it can influence all of the above factors.

PMID- 10881587
TI  - Assessment of disease activity and extent by magnetic resonance imaging in
      ulcerative colitis.
AB  - BACKGROUND: We determined whether magnetic resonance imaging (MRI) could
      determine the activity and site of involvement in ulcerative colitis. METHODS:
      Colonoscopy, double-contrast barium enema and gadodiamide-enhanced MRI were
      performed prospectively in six patients with ulcerative colitis, including three
      females aged 10-22 years, both in the active and the remission stages. RESULTS:
      Characteristic findings of MRI in the active stage of ulcerative colitis were
      loss of haustral markings and thickening and contrast enhancement of the colonic
      wall. In five of six patients, the site of disease distribution determined by MRI
      was in accordance with that determined by colonoscopy. CONCLUSIONS: Gadodiamide
      enhanced MRI is a safe and useful method of determining disease activity and
      extent in patients with ulcerative colitis.

PMID- 10881588
TI  - Altered anti-oxidant status and increased lipid peroxidation in marasmic
      children.
AB  - BACKGROUND: Protein energy malnutrition (PEM) is a common pediatric health
      problem in developing countries. Although the clinical features of PEM are well
      known, its pathophysiology is still unclear. Free radicals have been implicated
      in pathogenesis of PEM. In the present study, oxidant/anti-oxidant status in
      marasmus was investigated. METHODS: Red cell glutathione, glutathione peroxidase
      and superoxide dismutase and their related cofactors, serum selenium and copper,
      were studied in marasmic and control children. Serum lipid peroxidation was also
      evaluated to assess oxidative stress. RESULTS: The red cell glutathione levels
      and glutathione peroxidase activities were found to be significantly lower in the
      marasmic children than in the controls. Red cell superoxide dismutase (SOD)
      activity was not different between two groups. Serum selenium and copper
      concentrations were significantly lower in the marasmic children than in the
      control subjects. The malondialdehyde concentration, which is an index of lipid
      peroxidation, was significantly higher in the marasmic group compared with the
      controls. CONCLUSION: The anti-oxidant defense system was affected in marasmic
      children. Reduced anti-oxidant status and increased oxidative stress occurs in
      marasmic children.

PMID- 10881589
TI  - Relationship between serum leptin and thyroid hormones in children.
AB  - BACKGROUND: Because leptin decreases food intake and increases energy
      expenditure, the possible influence of thyroid status on the leptin system has
      been investigated mainly in adults and animals. However, the data available at
      present are very confusing. The aim of the present study was to assess the
      possible interaction of thyroid hormones with the leptin system. METHODS: Serum
      free thyroxine (FT4), a biologically active thyroid hormone, and thyroid
      stimulating hormone (TSH), a sensitive and reliable index of thyroid status, were
      examined in 51 children (19 males, 32 females) with mass screening-detected
      congenital hypothyroidism on continuous L-thyroxine (L-T4) substitution therapy.
      The subjects were divided into younger (n = 35, aged 1 month-5 years) and older
      (n = 16, 6 years-11 years) children groups. Serum levels of leptin and thyroid
      hormones were measured in the subjects. Body mass index (BMI) was estimated by
      the formula bodyweight (kg)/height x height (m2), which is known as the Kaup
      index in younger children and BMI in older children and adults. RESULTS: In the
      younger children group, serum leptin levels showed no correlation with serum TSH,
      FT4 or T4. In the older children group, serum leptin concentrations significantly
      correlated with T4 (r = 0.510, P < 0.05) and BMI (n = 16, r = 0.647, P < 0.01),
      but not with TSH or FT4. CONCLUSION: The role of thyroid hormones in modulating
      leptin synthesis and secretion seems to have little, if any, clinical or
      biological relevance.

PMID- 10881590
TI  - Kinetics of palmitic acid transport in insulin-dependent diabetic pregnancies: in
      vitro study.
AB  - BACKGROUND: The paucity of data relating to transport kinetics of free fatty
      acids (FFA) in pregnant diabetic women prompted the undertaking of the present
      study. METHODS: Transport kinetics of a model FFA, palmitic acid, have been
      investigated in Type I diabetic pregnancies, using in vitro perfusion of isolated
      placental lobules. National Cancer Tissue Culture medium diluted with Earle's
      buffered salt solution was used as the perfusate and control placental lobules
      were perfused for comparison. RESULTS: In five Type I diabetic women, the
      palmitic acid transport fraction (TF) averaged 5.6 +/- 0.42% of injected maternal
      bolus dose, representing 11.8 +/- 2.1% that of tritiated water used as reference.
      In control perfusions (n = 5), the palmitic acid TF represented 10.2 +/- 1.3% of
      tritiated water TF. Differential transport rates of palmitic acid for 10, 25, 50,
      75 and 90% of efflux in fetal veins differed significantly from the corresponding
      values for tritiated water in both study and control series. However, palmitic
      acid transport rates for the various efflux fractions in the two series were not
      significantly different. For kinetic parameters, such as area under the curve,
      clearance, elimination constant, time for maximum response, absorption rate and
      elimination rate, the values for palmitic acid in the diabetic and control series
      also did not differ significantly. CONCLUSION: Transport kinetics of palmitic
      acid in Type I human diabetic pregnancies in in vitro conditions do not differ
      significantly from those observed in normal pregnancies.

PMID- 10881591
TI  - Magnetic resonance imaging of brain lesions of a patient with hemolytic uremic
      syndrome following Escherichia coli O157 infection.

PMID- 10881592
TI  - Alpha heavy chain disease in a child.

PMID- 10881593
TI  - Hyperparathyroidism and cervical canal stenosis in twins with hypophosphatemic
      rickets.

PMID- 10881594
TI  - Japanese siblings with congenital chloride diarrhea.

PMID- 10881595
TI  - Bucillamine-induced nephropathy in a child with juvenile rheumatoid arthritis and
      Kartagener's syndrome.

PMID- 10881596
TI  - Sudden death of a patient in complete remission after anthracycline therapy for
      acute lymphoblastic leukemia.

PMID- 10881597
TI  - Sudden death of a 21-year-old female with Williams syndrome showing rare
      complications.

PMID- 10881598
TI  - Hypokalemic periodic paralysis and mutations in the CACNL1A3 gene: case study in
      a Japanese family.

PMID- 10881599
TI  - [Drug treatment of androgenetic alopecia in men].

PMID- 10881600
TI  - [Structure, function and potential therapeutic possibilites of NMDA receptors. 1.
      Architecture and modulation of receptors].

PMID- 10881601
TI  - [New genetically engineered drugs].

PMID- 10881602
TI  - [Quality control of drugs--the contribution of pharmacy to drug safety standards.
      The historical development of the working group on drug quality control-
      pharmaceutical analysis of the German Pharmaceutical Society. 1].

PMID- 10881603
TI  - Prevention of the degraded-contingency effect by signalling training trials.
AB  - Presentation of unsignalled unconditioned stimuli (USs) interspersed among
      Pavlovian excitatory conditioning trials weakens conditioned responding to a
      target conditioned stimulus (CS; Rescorla, 1968). However, signalling these
      intertrial USs with another cue (a cover stimulus) has been shown to alleviate
      this degraded-contingency effect (e.g. Durlach, 1982, 1983). In contrast to
      signalling the intertrial USs, the present experiments examined the effect on the
      degraded-contingency effect of signalling the target CS-US pairings. Experiment
      1, using parameters selected to avoid overshadowing, found that consistently
      presenting a cover stimulus immediately prior to the target CS-US pairings during
      degraded-contingency training alleviated the degraded-contingency effect.
      Experiment 2 examined the underlying mechanism responsible for this cover
      stimulus effect through posttraining associative inflation of the cover stimulus
      or the context, and found that inflation of the cover stimulus attenuated
      responding to the target CS (i.e. empirical retrospective revaluation). The
      results are discussed in terms of various acquisition- and expression-focused
      models of acquired responding.

PMID- 10881604
TI  - Positive and negative patterning in human causal learning.
AB  - Investigations of patterning discriminations by nonhuman animals have generally
      found that positive patterning is easier to learn than negative patterning.
      Studies of patterning discriminations in human causal learning tasks have failed
      to document any differences between positive and negative patterning. In the
      present study, human participants predicted an outcome on trials involving either
      a compound cue or its elements. Positive and negative patterning problems were
      successfully solved in a within-subjects design; negative patterning problems
      proved to be more difficult when an additional, 50% contingent cue was included
      (Experiment 2), but not when it was excluded (Experiment 1). Possible reasons for
      these results are discussed. The discussion concludes with an analysis of
      exemplar models (e.g., Pearce, 1994) of human causal learning and considers the
      conditions under which these models do and do not anticipate our results.

PMID- 10881605
TI  - Effects of varying the amount of preexposure to spatial cues on a subsequent
      navigation task.
AB  - In each of two experiments rats were preexposed to four compound landmarks (AX,
      BX, CX, and DX) one at a time; they were then trained to find a submerged
      platform located in a fixed position in a swimming pool using these same
      landmarks. When the preexposure was SHORT (4 sessions) it facilitated subsequent
      learning (a perceptual learning effect), whereas when rats were given a LONG
      preexposure phase (8 sessions) this facilitatory effect disappeared. EXTRA-LONG
      preexposure (16 sessions) reversed the facilitatory effect--that is to say, we
      observed retarded learning. The results show that rats' ability to navigate
      towards an invisible goal is affected by the length of their preexposure to the
      spatial cues that signal the location of the goal. These data are consistent with
      an associative analysis of the swimming pool navigation task.

PMID- 10881606
TI  - Overshadowing of subsequent events and recovery thereafter.
AB  - Four experiments using a conditioned lick suppression preparation with rats were
      conducted to examine whether overshadowing of subsequent events could be obtained
      in Pavlovian backward conditioning (i.e. unconditioned stimulus [US] before
      conditioned stimulus [CS]), and to determine whether such overshadowing could be
      reversed without further training with the overshadowed CS, as has been reported
      in overshadowing of antecedent events. In Experiment 1, a backward-conditioned CS
      overshadowed a second backward-conditioned CS. Two posttraining manipulations,
      extinction of the overshadowing CS (Experiment 2) and shifting of the temporal
      relationship of the overshadowing CS to the US (Experiment 3), increased
      responding to the overshadowed CS. These results constitute the first unambiguous
      demonstration of stimulus competition between subsequent events using first-order
      conditioning, and they show that, like overshadowing with forward conditioning,
      such overshadowing is due, at least in part if not completely, to a failure to
      express information that had been acquired.

PMID- 10881607
TI  - Stimulus exposure effects in human associative learning.
AB  - Learning that one cue (CS) predicts a second, salient cue (US) can often be
      slowed by prior exposure to one or both stimuli. In animals, CS-US learning is
      more strongly retarded following uncorrelated exposure to both CS and US than
      following exposure to the US alone. In this paper we present several studies
      showing a similar effect in humans, using a computer-based task. Experiments 1
      and 2 used a between-groups design and demonstrated a strong CS/US exposure
      effect, whether or not the US was signalled by a neutral cue during exposure.
      Experiment 3 demonstrated similar effects using a within-subjects design.
      Overall, these results are consistent with several theoretical interpretations
      and suggest that uncorrelated CS/US exposure leads to a robust retardation of
      subsequent CS-US learning in humans.

PMID- 10881608
TI  - Perceptual priming is not a necessary consequence of semantic classification of
      pictures.
AB  - Four experiments investigated how repetition priming of object recognition is
      affected by the task performed in the prime and test phases. In Experiment 1
      object recognition was tested using both vocal naming and two different semantic
      decision tasks (whether or not objects were manufactured, and whether or not they
      would be found inside the house). Some aspects of the data were inconsistent with
      contemporary models of object recognition. Specifically, object priming was
      eliminated with some combinations of prime and test tasks, and there was no
      evidence of perceptual (as opposed to conceptual or response) priming in either
      semantic classification task, even though perceptual identification of the
      objects is required for at least one of these tasks. Experiment 2 showed that
      even when perceptual demands were increased by brief presentation, the inside
      task showed no perceptual priming. Experiment 3 showed that the inside task did
      not appear to be based on conceptual priming either, as it was not primed
      significantly when the prime decisions were made to object labels. Experiment 4
      showed that visual sensitivity could be restored to the inside task following
      practice on the task, supporting the suggestion that a critical factor is whether
      the semantic category is preformed or must be computed. The results show that the
      visual representational processes revealed by object priming depend crucially on
      the task chosen.

PMID- 10881609
TI  - Manipulations of irrelevant information: suffix effects with articulatory
      suppression and irrelevant speech.
AB  - Numerous studies have demonstrated impaired recall when the to-be-remembered
      information is accompanied or followed by irrelevant information. However, no
      current theory of immediate memory explains all three common methods of
      manipulating irrelevant information: requiring concurrent articulation,
      presenting irrelevant speech, and adding a stimulus suffix. Five experiments
      combined these manipulations to determine how they interact and which theoretical
      framework most accurately and completely accounts for the data. In Experiments 1
      and 2, a list of auditory items was followed by an irrelevant speech sound (the
      suffix) while subjects engaged in articulatory suppression. Although articulatory
      suppression reduced overall recall compared to a control condition, comparable
      suffix effects were seen in both conditions. Experiments 3 and 4 found reliable
      suffix effects when list presentation was accompanied by irrelevant speech.
      Experiment 5 found a suffix effect even when the irrelevant speech was composed
      of a set of different items. Implications for working memory, precategorical
      acoustic store, the changing-state hypothesis, and the feature model are
      discussed.

PMID- 10881610
TI  - The rhyming skills of deaf children educated with phonetically augmented
      speechreading.
AB  - Two experiments investigated whether profoundly deaf children's rhyming ability
      was determined by the linguistic input that they were exposed to in their early
      childhood. Children educated with Cued Speech (CS) were compared to other deaf
      children, educated orally or with sign language. In CS, speechreading is combined
      with manual cues that disambiguate it. The central hypothesis is that CS allows
      deaf children to develop accurate phonological representations, which, in turn,
      assist in the emergence of accurate rhyming abilities. Experiment 1 showed that
      the deaf children educated early with CS performed better at rhyme judgement than
      did other deaf children. The performance of early CS-users was not influenced by
      word spelling. Experiment 2 confirmed this result in a rhyme generation task.
      Taken together, results support the hypothesis that rhyming ability depends on
      early exposure to a linguistic input specifying all phonological contrasts,
      independently of the modality (visual or auditory) in which this input is
      perceived.

PMID- 10881611
TI  - Prosody and parsing in coordination structures.
AB  - The effect of prosodic boundary cues on the off-line disambiguation and on-line
      parsing of coordination structures was examined. It was found that relative
      clauses were attached to coordinated object noun phrases in preference to second
      conjuncts in sentences like: The lawyer greeted the powerful barrister and the
      wise judge who was/were walking to the courtroom. Naive speakers signalled the
      syntactic contrast between the two structures by a prosodic break between the
      conjuncts when the relative clause was attached to the second conjunct. Listeners
      were able to use this prosodic information in both off-line syntactic
      disambiguation and on-line syntactic parsing. The findings are compatible with a
      model in which prosody has a strong immediate effect on parsing. It is argued
      that the current experimental design has avoided confounds present in earlier
      studies on the on-line integration of prosodic and syntactic information.

PMID- 10881612
TI  - The processing of interlexical homographs in translation recognition and lexical
      decision: support for non-selective access to bilingual memory.
AB  - In three experiments we looked at the processing of interlexical homographs by
      Dutch-English bilinguals. In Experiment 1 we employed the translation recognition
      task, a task that forces the participants to activate both language systems
      simultaneously. In this task the processing of interlexical homographs was
      inhibited substantially compared to the processing of matched control words,
      especially when the homograph reading to be selected was the less frequent of the
      homograph's two readings. In Experiments 2 and 3 we used the lexical decision
      task: In one condition we asked the participants to categorize letter strings as
      words or nonwords in Dutch; in a second condition we asked them to do so in
      English. The makeup of the stimulus set in Experiment 2 permitted the
      participants to ignore the instructions and to instantiate the task in a language
      neutral form--that is, to categorize the letter strings as words in either Dutch
      or English. Under these circumstances a small, frequency-dependent inhibitory
      effect for homographs was obtained, but only in condition Dutch. In Experiment 3
      the participants were forced in a language-specific processing mode by the
      inclusion of "nonwords" that were in fact words in the non-target language. Large
      frequency-dependent inhibitory effects for homographs were now obtained in both
      language conditions. The combined results are interpreted as support for the view
      that bilingual lexical access is non-selective.

PMID- 10881613
TI  - Parafoveal processing in word recognition.
AB  - Two experiments investigated the degree to which properties of a word presented
      in the parafovea influenced the time to process a word undergoing concurrent
      foveal inspection. In Experiment 1, subjects viewed a set of five-letter words at
      a fixed point, with words in parafoveal vision varying in length, word frequency,
      and both the type and token frequency of occurrence of their initial three
      letters. The results showed that the frequency of the target and the type
      frequency of its initial letters influenced foveal fixation time. In Experiment
      2, subjects executed a sequence of saccades before initial fixation on the
      experimental items. Under these circumstances, fixation time was shorter overall.
      Lexical properties of parafoveal words had no effect on foveal processing, but
      the length and the type frequency of their initial letters exerted a strong
      influence. Parafoveal-on-foveal effects of this form are incompatible with models
      of reading in which attention is allocated sequentially to successive words. The
      data are more consistent with the proposition that foveal and parafoveal
      processing occurs in parallel, with processing distributed over a region larger
      than a single word. Subsidiary analyses showed little influence of any of the
      manipulated variables on saccade extent.

PMID- 10881614
TI  - The development of the use of long-term knowledge to assist short-term recall.
AB  - The influence of item familiarity upon memory span was examined in adults and
      children aged 5, 7, and 10 years by comparing the recall of words and nonwords.
      Using a probed recall task, both item recall and position recall were tested. The
      effect of familiarity upon item recall was found to develop with age, from no
      effects in the 5-year-olds to significant effects in the older children and
      adults. By contrast, no effect of familiarity was found at any age when recall of
      position was required. Dissociations between word length effects and familiarity
      effects supported the conclusion that the familiarity effect does not result from
      rehearsal. Several explanations for the source of the familiarity effect were
      examined, and the familiarity effect was attributed to a strategic redintegration
      or reconstruction process, which is necessary for item recall but not for
      position recall.

PMID- 10881615
TI  - Long-term memory for spatial and temporal mental models includes construction
      processes and model structure.
AB  - There is a strong case that people construct and manipulate mental models in
      working memory but relatively little evidence that mental models are preserved in
      long-term memory. Instead people may remember an episodic construction trace: a
      record of the operations used to construct a mental model (Payne, 1993).
      Experiment 1 investigated memory for determinate spatial descriptions (which
      describe a single configuration of objects) and indeterminate spatial
      descriptions (which describe two equally plausible configurations). Recognition
      performance was impaired when the overlap between the episodic construction trace
      of a description at learning and at test was disrupted by reordering the
      sentences within a description. Participants were better at remembering the gist
      of determinate descriptions than that of indeterminate descriptions. For
      indeterminate descriptions, provided differences in gist recognition were
      controlled, participants showed better memory for the original description.
      Experiment 2 showed a similar pattern of results with temporal descriptions. A
      third experiment manipulated the similarity between foils in the recognition test
      and the original descriptions to provide further evidence for both episodic
      construction trace and remembered mental models. In combination, these results
      favour a hybrid account of memory for mental models, which includes information
      about both construction processes and model structure.

PMID- 10881616
TI  - When inverted faces are recognized: the role of configural information in face
      recognition.
AB  - The identification of upright faces seems to involve a special sensitivity to
      "configural" information, the processing of which is less effective when the face
      is inverted. However the precise meaning of "configural" remains unclear. Five
      experiments are presented, which showed that the disruption of the processing of
      relational, rather than holistic, information largely determines the occurrence
      as well as the size of the face-inversion effect. In Experiment 1, faces could be
      identified either by unique combinations of local information (e.g. a specific
      eye colour plus hair colour) or by unique relational information (e.g. nose-mouth
      distance). The former showed no inversion effect, whereas the latter did. A
      combination of local and relational information (Experiment 2) again produced an
      inversion effect, although this effect was smaller than that found when only
      relational information was used. The results were replicated in Experiment 3 when
      differences in the brightness of local features were used instead of specific
      colour combinations. Experiment 4 used different retrieval conditions to
      distinguish relational from holistic processing, and demonstrated again that
      spatial relations between single features appeared to provide crucial information
      for face recognition. In Experiment 5, the importance of relational information
      was confirmed using faces that also varied in the shapes of local features.

PMID- 10881617
TI  - Global-local orientation congruency effects in visual search.
AB  - In a visual search task, subjects had to decide which of 2 possible target
      letters was presented among 12 distractor letters. The 13 characters were
      arranged to form a global Navon-type letter. The global letter and the local
      letters (target and distractors) were independently presented in four different
      viewer-related orientations. When the global letter and the target were
      frequently congruently oriented, the response times increased with growing
      orientation disparity between them. This global-target congruency effect was
      independent from target identity (Experiment 1), and it diminished when global
      and target orientations were not correlated (Experiment 2). The results indicate
      that the orientation of the global letter can be deliberately used in order to
      facilitate the processing of congruently oriented local targets. The alignment of
      a spatial frame of reference is discussed as the most probable process underlying
      this facilitation.

PMID- 10881618
TI  - An examination of hypervigilance for external threat in individuals with
      generalized anxiety disorder and individuals with persecutory delusions using
      visual scan paths.
AB  - One account of generalized anxiety disorder (GAD) is that it results from
      hypervigilance, manifest as excessive scanning of the external environment and
      preferential attention to threat. However, for individuals with GAD, there has
      been no direct study of scanning, and evidence for preferential attention to
      threat has only been found for threat-words. We therefore devised a new measure
      of hypervigilance. Visual scan paths were recorded of individuals with GAD (N =
      12) and people without a psychiatric illness (N = 12) viewing complex pictures
      that varied in threat content. People with persecutory beliefs (N = 11) also
      participated in the study to test the hypothesis that anxiety, via such
      hypervigilant cognitive processes, may contribute to the maintenance of
      delusions. Compared with the control group, the anxious individuals were not
      found either to scan excessively for or to look at threat. The anxiety group was
      therefore not hypervigilant for external threat, which is inconsistent with the
      hypervigilance model. As a consequence, the hypothesis that anxiety maintains
      delusions was not tested. However, additional support was found for the
      hypothesis that people with delusions form rapid judgements on the basis of less
      data-gathering than control groups who are either anxious or have no psychiatric
      illness.

PMID- 10881619
TI  - Stimulus-response compatibility for absolute and relative spatial correspondence
      in reaching and in button pressing.
AB  - Three experiments tested whether stimulus-response (S-R) compatibility might be a
      function of absolute (as opposed to relative) spatial correspondence--that is,
      the distance between a stimulus and the place of response. Experiment 1 studied
      reaching movements toward one of two targets in response to one of six visual
      stimuli. Stimulus-response pairs that shared relative position were faster than
      those that did not, and reaction time was faster when the stimulus and one of the
      potential targets were in close proximity. In Experiment 2 the same effects were
      found when the hands started from a different position, implicating stimulus
      target distance, rather than stimulus-hand distance as the critical variable.
      Experiment 3 employed keypress responses instead of reaches, and the distance
      effect was nearly absent. The implications of these results are discussed in
      terms of categorical (e.g. left-right) vs. quantitative (e.g. distance) S-R
      variables in spatial compatibility.

PMID- 10881620
TI  - An assessment of the attention demands during random- and blocked-practice
      schedules.
AB  - The reported study used the dual-task methodology to assess the attention demands
      associated with high and low contextual interference (CI) practice environments.
      Two specific issues were addressed. First, is there a difference in the attention
      demands during random and blocked schedules of practice? Second, what is the time
      course of any differential attention demands that emerge during random and
      blocked training? In order to address these questions two specific temporal loci
      were probed during practice: a pre-response interval and the inter-trial
      interval. It was assumed that the pre-response interval contained the
      reconstructive activity that is central to the reconstruction position. In
      contrast, the inter-trial interval has been interpreted in previous work to be
      the interval in which critical intra- and inter-item processing is performed
      during random practice. The data revealed a typical CI effect for the primary key
      pressing task. Specifically, blocked-practice participants displayed superior
      performance during training but performed less well than the random-practice
      individuals at the time of retention. The poorer acquisition performance of the
      random-practice participants was associated with higher cognitive demand during
      both the pre-response and the inter-trial intervals than that of individuals
      assigned to blocked practice. The greater attention demands for random-practice
      individuals are discussed with respect to processes that might occur in both the
      pre-response and the inter-trial intervals.

PMID- 10881621
TI  - Hepatitis E virus: recent advances.

PMID- 10881622
TI  - Hormonal receptors in carcinoma of the gallbladder.

PMID- 10881623
TI  - Helicobacter pylori infection in the Indian population.

PMID- 10881624
TI  - Aetiological spectrum of chronic liver disease in eastern India.
AB  - AIM: To evaluate the aetiologic spectrum of chronic liver disease (CLD) in a
      tertiary referral center in Eastern India. METHODS: A total of 175 patients
      (cirrhosis 166, chronic hepatitis 9) diagnosed by clinical, biochemical,
      radiological and histopathological (42 cases) parameters were evaluated for
      aetiology. Investigations included: HBsAg and anti HCV (third generation) by
      ELISA. HBeAg and HBV DNA were tested in HBsAg positive patients. HCV RNA was
      tested in anti-HCV positive patients. Markers for autoimmune and Wilson's disease
      (anti-nuclear antibody, anti smooth muscle antibody, serum ceruloplasmin, urinary
      copper and slit lamp examination for KF ring) were done where clinically
      indicated. RESULTS: A total of 62 (35.4%) patients had HBV related CLD and 6
      (9.7%) of them had pre-core mutant. HCV was present in 17/114 (14.9%) cases and
      none had infection with both viruses. Autoimmunity, Wilson's disease and alcohol
      were the aetiological factors in 5 (2.8%), 5 (2.8%) and 3 (1.7%) patients
      respectively. No aetilogy could be found in 18/114 (15.8%) patients. CONCLUSIONS:
      It is concluded that HBV is the commonest cause of CLD in Eastern India. Alcohol
      and HCV are uncommon in this part of the country.

PMID- 10881625
TI  - Age related seroprevalence of antibodies to hepatitis A virus in Hyderabad,
      India.
AB  - BACKGROUND: Hepatitis A virus (HAV) is an enterically transmitted viral disease
      endemic in many developing countries including India. Infection is often
      subclinical or asymptomatic in children while with increasing age symptomatic
      acute infections are more common. In some developing countries improvements in
      living conditions have led to change in epidemiology of HAV infection. In our
      country there are very few reports on prevalence of HAV. OBJECTIVE: The present
      study was undertaken to determine the seroprevalence of hepatitis A virus
      antibodies in relation to age in Hyderabad. MATERIAL AND METHODS: Serum samples
      were collected from 90 subjects in the age group 2-64 years in a mass vaccination
      camp for Hepatitis B. All the subjects were investigated with a uniform social
      and medical history questionnaire. Sera were tested for antibody to HAV (total
      anti-HAV) using enzyme immunoassay (General Biologicals, Taiwan). RESULTS: The
      subjects included 48 males and 42 females. There were 54 children (< 12 yrs) and
      36 adults. Of the 90 serum samples tested 51 (56%) were positive for anti HAV
      antibodies. The seropositivity in males and females was similar. The
      seroprevalence was 31.8% (17/54) in children (< 12 years) and 94.4% (34/36) in
      adults (p < 0.001). Age related seroprevalence revealed that a majority of
      children below 10 years (33/48, 69%) remain anti HAV negative, while only 25% of
      children below 15 years were anti HAV negative. The anti HAV antibody positivity
      was similar in different income groups. CONCLUSION: The prevalence of HAV is high
      in Hyderabad. A majority of children below 10 years and 25% of children < 15
      years remain susceptible to HAV infection. Child immunization against HAV
      therefore should be considered in our population too.

PMID- 10881626
TI  - Gallbladder carcinoma: experience of 116 cases.
AB  - BACKGROUND: Aggressive surgical treatment is now being advocated even for
      advanced carcinoma gall bladder (GBC). We reviewed our data of GBC over the last
      5 years to analyse patient and survival characteristics in our patients. PATIENTS
      AND METHODS: Case records of all cases of GBC admitted to surgical wards in our
      hospital between 1994 to 1998 were reviewed for details such as age, sex,
      religion, symptoms, signs, investigations, treatment and survival. World
      literature was reviewed by using Medline search of the subject. RESULTS: A total
      of 116 patients with confirmed GBC were admitted during these five years. Their
      mean age was 54 +/- 11 years. Females greatly outnumbered males. The commonest
      symptom was abdominal pain (95%) followed by GB mass (78%). Associated gallstones
      were present in 67% cases. Adenocarcinoma was the commonest variety (79%). CT
      scan and USG were helpful in 78% and 89% cases respectively. Maximum patients
      (67%) presented with Nevins' stage V and most of these were treated with
      supportive therapy only. CONCLUSIONS: Our patients were at least a decade younger
      than patients in other series and presented at an advanced stage. Radiological
      investigations (USG and CT scan) played a vital role in diagnosing or suspecting
      the disease. Curative resections were performed in few cases. Our own results,
      though limited favour an aggressive surgical approach. Based on our observations
      we have recommended certain cancer preventive steps and future treatment
      strategies.

PMID- 10881627
TI  - Pulmonary function changes after large volume paracentesis.
AB  - OBJECTIVE: To study the effect of large volume paracentesis (LVP) on pulmonary
      function in patients with cirrhosis of liver and tense ascites. METHODS: Ten
      patients having alcoholic cirrhosis with ascites were subjected to LVP (mean 6.3
      +/- 0.3 L). Pre and post paracentesis spirometry and arterial blood gas analysis
      were performed and compared. RESULTS: Baseline mean lung volumes and arterial pO2
      were reduced from normal predicted values. Air flow was found normal. After LVP,
      an increase in absolute values of vital capacity, forced expiratory flow in first
      second (FEV1) and peak expiratory flow was observed; only the improvement in FEV1
      was significant p 0.05). Arterial pO2 also showed significant (p < 0.01)
      improvement after LVP. CONCLUSION: LVP leads to improvement in measured pulmonary
      function.

PMID- 10881629
TI  - Idiopathic haemochromatosis with unusual CT findings.
AB  - Hemochromatosis is rarely seen in India. We report a case of idiopathic
      hemochromatosis with increased urinary porphyrins. The computed tomography of the
      kidneys revealed high attenuating specks at the tip of papillae, the significance
      of which is discussed. This is also the first case report of the disease
      occurring in a female patient from India.

PMID- 10881628
TI  - Helicobacter pylori infection in chronic smokers with non ulcer dyspepsia.
AB  - BACKGROUND/AIMS: Both H. pylori infection and smoking are risk factors for acid
      peptic disorders. There is paucity of data on relationship between smoking and H.
      pylori infection. Therefore, we studied prevalence of H. pylori infection in
      smokers with non-ulcer dyspepsia (NUD). PATIENTS AND METHODS: 30 smokers with NUD
      (age 29.5 +/- 1.2 years; all men) and 30 non-smokers with NUD (age 29.2 +/- 1.6
      years; all men) were included. None was on antiulcer drugs or antibiotics for
      more than 2 weeks. Upper gastrointestinal endoscopy was performed and antral
      biopsies obtained were subjected to rapid urease test, Gram's staining, culture
      and histopathology. Patient was considered H. pylori positive, if culture was
      positive or combination of histopathology plus rapid urease test or Gram's
      staining plus rapid urease test was positive. RESULTS: 24 of 30 (80%) smokers and
      13 of 30 (43%) non smokers were positive for H. pylori infection (p < 0.001).
      There was no significant difference in the positivity of H. pylori in light
      (78%), moderate (81%) and heavy smokers (80%). All the 37 patients who were
      positive for H. pylori had histological gastritis compared to 65% in H. pylori
      negative patients. However there was no difference in presence of histological
      gastritis among H. pylori negative smokers (33%) and non smokers (70%; p = NS).
      CONCLUSIONS: H. pylori infection is more common in smokers with NUD than in non
      smokers. However duration and amount of smoking has no relationship with H.
      pylori positivity.

PMID- 10881630
TI  - Gastroduodenal artery pseudoaneurysm: metal coil embolization.

PMID- 10881631
TI  - Spider angiomas in the gastrointestinal tract.
AB  - Spider angiomas are cutaneous manifestations of endocrine imbalances in
      cirrhosis. We describe unusual cases of massive bleed from spider angiomas in the
      oral cavity and colon in association with cirrhosis of liver.

PMID- 10881632
TI  - Primary splenic hydatid in adults.

PMID- 10881633
TI  - Role of operative flexible choledochoscopy in calculous biliary tract disease.
AB  - BACKGROUND: In India, no study is available regarding the use of operative
      choledochoscopy in the management of choledocholithiasis. ERCP facilities are not
      always available at many centres and usually require the expertise of a medical
      gastroenterologist. In contrast, operative choledochoscopy is a simpler procedure
      that can easily be learned and practised by many surgeons at the time of CBD
      exploration. AIMS: To study the role of the flexible choledochoscopy in the
      diagnosis and management of calculous biliary tract disorders. METHODS: Twenty
      four patients with choledocholithiasis underwent flexible choledochoscopy. Stones
      were removed either with Desjardin's forceps or by choledochoscopic
      instrumentation. Postoperative T-tube cholangiography was done to detect any
      retained stones. RESULTS: Flexible choledochoscopy was performed in a total of 24
      patients. Choledochoscopy was done through a choledochotomy in 23 and through the
      cystic duct in one patient. The choledochoscope was used following conventional
      CBD exploration in 18 of the 23 patients. Complete clearance of stones was
      confirmed by choledochoscopy in 12 of the 18 patients and additional stones were
      seen in the remaining 6 patients. Fogarty balloon catheter and Dormia forceps
      were used to extract these stones. A CBD stricture was seen in 4 of these 18
      patients and choledochoscopic biopsy was done in one of them. In 5 of the 23
      patients, the choedochoscope was used as the initial exploring instrument.
      Impacted CBD stones were detected in 3 of the 5 patients, external compression of
      the CBD due to periampullary carcinoma in one and stones in both the ampulla and
      common hepatic duct in the last patient. Postoperative T-tube cholangiography was
      done in 10 patients and did not reveal any retained stones. Drainage procedures
      were carried out in 13 patients: 11 had choledochoduodenostomy and 2 had
      transduodenal sphincteroplasty. Choledochoscopy was a direct aid in choosing the
      operative procedure in 21 patients. CONCLUSIONS: Flexible choledochoscopy is the
      most effective method of CBD exploration and is essential in all patients with
      choledocholithiasis. No additional morbidity or mortality is caused by this
      procedure.

PMID- 10881634
TI  - Small cell carcinoma of oesophagus: report of a rare case.

PMID- 10881635
TI  - Adjuvant interstitial brachytherapy in a case of anorectal melanoma.
AB  - PURPOSE: A locally resectable case of anorectal melanoma is reported. In order to
      prevent local recurrence, interstitial brachytherapy was used. METHOD: A 45 years
      old emaciated female presented with a 8 x 6 x 6 cm, hard, mobile, intraluminal
      mass in the anal canal and rectum, biopsy revealed malignant melanoma. As the
      mass was locally resectable, wide local excision of the tumour was carried out.
      She was subsequently given interstitial brachytherapy with Caesium--137 implants
      at tumour bed, not described so far in literature. Six months later her general
      condition had improved but abdomino-perineal resection was necessitated due to
      presence of extra-rectal metastasis. RESULTS: Patient is in our follow-up for 36
      months now and doing well. CONCLUSION: Supplementation of interstitial
      brachytherapy after local resection of ano-rectal melanoma may help to prevent
      local recurrence.

PMID- 10881636
TI  - Amoebic liver abscess: is response to metronidazole declining?

PMID- 10881637
TI  - A breastfeeding strategy for Northern Ireland.

PMID- 10881638
TI  - Singular beneficence? Presidential address to the Ulster Medical Society
      delivered on Thursday, 14 October 1999.

PMID- 10881639
TI  - A review of 100 consecutive free tissue transfers.
AB  - Following the introduction of microsurgical techniques the availability of free
      tissue transfer has radically transformed reconstructive possibilities for both
      oncological and surgical defects. This study is a review of 100 consecutive free
      tissue transfers (free flaps), carried out in 96 patients over a period of 25
      months in our unit. The indications for surgery in this series mainly resulted
      from malignancy, trauma, chronic osteomyelitis, burns and congenital
      abnormalities. The tissues transferred included various combinations of skin,
      fat, fascia, muscle, bone and several free digits. Fourteen cases required re
      exploration, of which 12 were salvaged, and the overall success rate was 96%.

PMID- 10881640
TI  - The prevalence and types of coronary artery anomalies in Northern Ireland.
AB  - Coronary artery anomalies are uncommon, with a reported prevalence ranging from
      0.2% to 1.6%. It is important that those who undertake coronary angiographic
      procedures are aware of the spectrum of these anomalies. Interventional
      percutaneous coronary revascularisation procedures are widely used in the
      management of patients with symptomatic coronary atherosclerosis. The presence of
      a coronary artery anomaly may make these procedures technically challenging. We
      have reviewed the Cardiac catheterisation database at the Royal Victoria
      Hospital, Belfast, and report the prevalence and types of these anomalies.

PMID- 10881641
TI  - The incidence of cardiac lesions in infants born with major gastrointestinal
      malformations in Northern Ireland.
AB  - There is a recognised association between major gastrointestinal (GI)
      malformations and congenital heart disease (CHD). A retrospective study over 10
      years involving 240 infants born with gastrointestinal malformations was
      conducted in the Royal Belfast Hospital For Sick Children (RBHSC). We felt it was
      important to look at the incidence of CHD diagnosed in the infants presenting to
      the tertiary referral centre in Belfast. Comparable figures for the incidence of
      CHD associated with major GI malformations was found in the literature.

PMID- 10881642
TI  - Episiotomy repair: Vicryl versus Vicryl rapide.
AB  - Women suffer a significant degree of perineal morbidity in the postpartum period.
      For some, it can be significant and interfere with daily activities. Although
      there seems to be no doubt that polyglycolic acid derivatives are superior to non
      absorbable sutures with regard to wound healing, problems still occur with their
      use. In this study a relatively new product, Vicryl rapide, was compared with
      Vicryl.

PMID- 10881643
TI  - Motherhood in the teens and twenties: some surprises.
AB  - We report a study of the association of health and social support variables with
      motherhood in teenagers and older mothers. Both teenage and older mothers
      reported poorer physical and mental health and fewer and less frequent social
      contacts than their nulliparous peers. Contrary to expectation, however, older
      mothers reported less extensive and less adequate social support networks than
      did teenagers.

PMID- 10881644
TI  - Screening for hyperglycaemia in pregnancy: analysis of two screening protocols
      and review of current methods.
AB  - We assessed the ability of two screening protocols to detect varying degrees of
      hyperglycaemia in pregnancy and to compare fetal outcome in those found to have
      normal and abnormal glucose metabolism by either protocol. 493 pregnant women
      were identified by one of two screening protocols to be at risk of hyperglycaemia
      in pregnancy. Pregnancy complications, induction of labour, method of delivery,
      birth weight, incidence of congenital anomalies and neonatal complications were
      assessed; there were no significant differences between those with normal and
      abnormal glucose metabolism detected by either protocol apart from a significant
      linear trend for the incidence of large for gestational infants with increasing
      hyperglycaemia in both groups. Protocol B was as effective in detecting new
      hyperglycaemia in pregnancy as Protocol A. It involved the use of a breakfast
      meal profile in the initial assessment of those screened positive, reducing the
      need for glucose tolerance tests in the vast majority of cases. In the population
      studied, hyperglycaemia in pregnancy was not associated with adverse fetal
      outcome.

PMID- 10881645
TI  - Fever hospitals in counties Armagh and Down: 1817-39.
AB  - This paper outlines the provision for fever patients, (other than those suffering
      from cholera during the epidemic of 1832-34), in counties Armagh and Down in the
      two decades prior to the introduction of the Poor Law to Ireland. Possible causes
      of fever and the numbers of patients treated are discussed. The establishment and
      location of fever hospitals and the state of the premises are considered and an
      assessment of the contribution of these institutions to the development of
      medical provision in the early nineteenth century is also provided.

PMID- 10881646
TI  - Life-threatening laryngeal oedema in a pregnant woman with hereditary angioedema.

PMID- 10881647
TI  - Primary squamous carcinoma of the thyroid.

PMID- 10881648
TI  - An unusual case of late graft infection.

PMID- 10881649
TI  - Diagnostic dilemma of hyperamylasaemia in acute abdominal emergencies.

PMID- 10881650
TI  - Benign liver lesions in female patients.

PMID- 10881651
TI  - Bouveret's syndrome: gallstone ileus causing gastric outlet obstruction.

PMID- 10881652
TI  - Neonatal diabetes mellitus.

PMID- 10881653
TI  - Ureteric kinking after colposuspension: a case report and review of the
      literature.

PMID- 10881654
TI  - [Medical Genetic Center of Russian Medical Science Academy is 10 years old].

PMID- 10881655
TI  - [Influence of population's genetic structure on the load size of monogenic
      hereditary diseases in Russia].
AB  - The paper presents the results of genetic and epidemiological study of
      populations in 5 Russian regions: the Kirov, Kostroma, and Bryansk Provinces,
      Krasnodar Territory, and the Republic of Mari El. The total size of the study
      population was over 1.5 million. Random inbreeding (Fst) in all Russian rural
      populations was significant and varied from 0.34 x 10(-3) to 7.6 x 10(-3). The
      prevalence rates for autosomal dominant (AD) disorders ranged from 0.22 to 3.93
      per 1000. The load of autosomal recessive (AR) disorders varied from 0.17 to
      2.01. The prevalence rates for AD and AR disorders was twice lower in the urban
      populations than those in the rural ones. The prevalence of X-linked recessive
      disorders was 0.33 per 1000 males. An analysis was made to examine the
      correlation between inherited diseases and Fst. The Pierson correlation
      coefficient was 0.81 and 0.87 for AD and AR disorders, respectively. The
      regression suggested that genetic differentiation of the populations with genes
      for hereditary disorders is partially related to gene drift. This suggestion was
      proved by genetic geographical mapping analysis. The similarity in the patterns
      of genetic distance distribution for all 3 genetic systems was revealed by the
      correlation coefficients between the maps for neutral genetic markers and the
      genes of AD and AR disorders which were equal to 0.67 and 0.65. There was the
      highest correlation coefficient between the maps of genetic distances for the
      genes of AD and AR disorders (Rs = 0.88).

PMID- 10881656
TI  - [Information and retrieval diagnostic system for inherited metabolic diseases].
AB  - The paper analyzes a procedure for construction and practical use of an
      information and retrieval diagnostic system (IRDS) for inherited metabolic
      diseases (IMD) in the context of an automatic working place for consulting
      genetics. An IRDS structure for IMD is proposed, which involves the following
      functional elements: 1) a genetic register; 2) an inherited metabolic disease
      database (IMDD); 3) a special module for searching for the probable range of
      diagnoses; 4) an archive; 5) a special model for statistical analysis of the
      clinical polymorphism of IMD. The full insight into each nosological entity (n =
      316) as part of IMD IRDS is gained by using a set of catalogues, such as a
      catalogue IMD classes (n = 22), that of IMD clinical symptoms and signs (n =
      1215); that of IMD biochemical markers (n = 934); a list of all symptoms and
      signs for each nosological entity; that of major diagnostic signs for each
      nosological entity. The clinical picture is described within the framework of the
      unified structure that includes the following set of items: the textual
      description of the clinical picture of a disease in terms of major diagnostic
      signs, etiology, genetics, pathogenesis, a biochemical phenotype, paraclinical
      studies, differential diagnosis, treatment, and prevention. The system is
      provided with a simple and user-friendly interface that allows a user to have a
      prompt look at the data pertaining to each nosological entity, to find required
      references by employing multiple keys of data search, sort, and printing.

PMID- 10881657
TI  - [Ribosomal genes in the human genome: contribution to genetic individuality and
      phenotypic manifestation of gene dosage].

PMID- 10881658
TI  - [New approach to evaluating mutagenicity by cytogenetic techniques].
AB  - A two-population model that satisfactorily describes the emergence of
      multiaberrant cells during spontaneous mutagenesis is proposed. The model is
      based on the conception of existence of two cell populations. In the first basic
      part, the cells are distributed by the Poisson law. In the second rather small
      part, those are distributed in a geometric fashion. It is suggested that such
      distributions result from mutations in reparation and replication genes. These
      mutations determine higher incidence of chromosomal aberrations distributed by
      the geometrical law.

PMID- 10881659
TI  - [Genetic polymorphism and occupational diseases: results of 10-years studies].
AB  - The paper presents the results of investigations made at the Laboratory of
      Environmental Genetics, Medical Genetic Research Center, Russian Academy of
      Medical Sciences, to search for the markers of genetic predisposition or
      resistance to a number of occupational diseases (asbestosis, occupational
      fluorosis, silicosis, dust-induced bronchitis, bronchial asthma).

PMID- 10881660
TI  - [Pattern of hereditary reproductive disorders].
AB  - A comprehensive clinical, endocrinological, and medical genetic studies were made
      in 678 patients with reproductive disorders and infertility. A schedule was
      developed to examine the patients with successive current cytological,
      cytogenetic, molecular cytogenetics and molecular genetic methods. The pattern
      and proportion of chromosomal and genic abnormalities were defined among the
      total number of patients with reproductive disorders.

PMID- 10881661
TI  - [Investigation of fetal cells isolated from maternal blood by different methods].
AB  - This paper presents the results of investigation of the isolated from maternal
      blood by 4 different methods according to the optimized protocols. All women had
      male fetuses. The mononuclear cells with fetal erythroblasts were preisolated by
      using density-gradient centrifugation of the maternal blood in the Ficoll
      solution. Fetal cells were detected by FISH for Y-chromosomal sequences. The
      fetal cells were 2.1% by fluorescence activated cell sorting (FACS); 3.8% by
      magnetic field sorting, and 2.6% by two-stage density gradient precipitation. The
      fetal lymphocytes were investigated through air-cultivation of peripheral
      maternal lymphocytes. Their proportion was 3.9% in the culture samples. The
      findings lead to the conclusion that the new non-invasive approach is useful for
      prenatal diagnosis of chromosomal aneuploidies.

PMID- 10881662
TI  - [Immunologic monitoring of patients with cystic fibrosis: value of different
      laboratory findings].
AB  - Cystic fibrosis (CF) is a common, serious, and frequently fatal autosomal
      recessive genetic disorder associated with the poor function of chloride
      channels. Chronic endobronchial inflammation and bacterial infection are main
      causes of morbidity and mortality due to CF. The study dealt with a relationship
      between progression and inflammation markers. Twenty one CF children with acute
      pulmonary exacerbation were examined. The signs of peripheral blood inflammation
      (responses of lymphocytes to PHA and their sensitivity to the antiproliferative
      effect of glucocorticoids) and in situ inflammation markers (sputum elastase
      activity, IL-8 and TNF-alpha, and protein concentrations in the same sputum
      specimens). These laboratory findings were used to calculate a "laboratory index"
      (LI). The clinical status of each patient was evaluated with a "clinical index"
      (CI), a parameter that includes respiratory secretion cultures, pulmonary
      function test results, nutritional status, and the presence of disease-related
      complications. There was a positive linear correlation between LI and CI. The
      presence of P. aeruginosa was strongly associated with the changes of
      inflammatory markers. CF patients with prolonged P. aeruginosa infection
      demonstrated extremely enhanced elastase activity and elevated amounts of sputum
      IL-8 and TNF-alpha as compared to uninfected subjects. The lung elastase
      activities, sputum protein contents, and TNF-alpha levels in individuals with
      short-term colonization were at or below those without P. aeruginosa infection.
      In patients with or without short-term colonization, the normalization of
      laboratory parameters was strongly related to evident clinical improvement. At
      the same time, antibiotic treatment failed to suppress an excessive inflammatory
      response in the lungs of patients with prolonged P. aeruginosa infection. The
      importance of individual inflammation markers is discussed in the paper.

PMID- 10881664
TI  - Eradication of dracunculiasis.

PMID- 10881663
TI  - [Study of CATCH 22: genetic aspects].
AB  - Introducing molecular genetic techniques into clinical practice has made it
      possible to detect del 22q11.2, an etiological factor for congenital
      cardiovascular diseases in CATCH 22. The authors' complex (clinical,
      syndromological, molecular genetic, and computed) approach to examining this
      group of syndromes has enabled patients at high risk for CATCH 22 to be
      identified. A list of gene candidates responsible for manifestations of CATCH 22
      and data on how pathological phenotypes are developing in model objects are
      presented.

PMID- 10881665
TI  - Adolescent immunization.

PMID- 10881666
TI  - Angiogenesis in Oncology and Hematology. Transplantation in Hematology and
      Oncology II: From Novel Strategies to Clinical Trials. 8-11 April 2000, Munster,
      Germany. Abstracts.

PMID- 10881667
TI  - 9th International ANCA Workshop. Groningen, The Netherlands, 12-15 April 2000.
      Abstracts.

PMID- 10881668
TI  - Scandinavian Society for the Study of Diabetes 35th annual meeting. Oslo, Norway.
      5-7 May 2000. Abstracts.

PMID- 10881669
TI  - 45th Annual meeting of the Health Physics Society. Denver, Colorado, USA. 25-29
      June 2000. Abstracts.

PMID- 10881670
TI  - Annual conference of The British Cardiac Society. Glasgow, 15-18 May 2000.
      Abstracts.

PMID- 10881671
TI  - Orthopaedic proceedings, 1998, 1999.

PMID- 10881672
TI  - 47th Annual meeting of the Society of Nuclear Medicine. St. Louis, Missouri, USA.
      June 3-7, 2000. Abstracts.

PMID- 10881673
TI  - British Society for Rheumatology XVIIth Annual General Meeting and the British
      Health Professionals in Rheumatology Spring Meeting. Brighton, United Kingdom, 9
      12 May 2000. Abstracts.

PMID- 10881674
TI  - Investigation into the mode of action of R-91650, an arylpiperazinyl
      fluoroquinolone, on feline immunodeficiency virus replication inhibitory
      activity.
AB  - The mode of action of R-91650, an arylpiperazinyl fluoroquinolone, on feline
      immunodeficiency virus (FIV) replication inhibitory activity was investigated. R
      91650 inhibited replication of FIV at non-cytotoxic concentration levels in both
      acutely infected peripheral blood mononuclear cells and chronically infected P
      CrFK cells. The compound reduced the intracellular p24 concentration levels in P
      CrFK cells in a dose-dependent manner. Northern blot analysis revealed that R
      91650 selectively prevented the accumulation of FIV mRNA in P-CrFK cells.
      However, the compound did not inhibit FIV-long terminal repeat (LTR) promoter
      activity in the reporter gene expression analysis. These data suggest that R
      91650 is a novel inhibitor of FIV replication that inhibits a certain step or
      steps following transcription initiation of the FIV-LTR promoter.

PMID- 10881675
TI  - Determination of the complete nucleotide sequence of a vaccine strain of porcine
      reproductive and respiratory syndrome virus and identification of the Nsp2 gene
      with a unique insertion.
AB  - The complete nucleotide sequence of the genomic RNA of a vaccine strain (SP) of
      porcine reproductive and respiratory syndrome virus (PRRSV) was determined. It
      shares approximately 94% identity of nucleotide sequence with two recently
      reported North American strains, 16244B and VR2332, but only 78% with a European
      strain, Lelystad virus (LV). Its genome is the longest among the four published
      complete sequences of PRRSV, due to an insertion in the Nsp2-encoding region.
      Compared to Nsp2 of the North American strains and the European strain, the
      predicted Nsp2 of strain SP contains 36 and 155 amino acid insertions,
      respectively, near the C-terminus, in addition to several highly variable
      regions. The insertion shows no homology with any equivalent arterivirus
      proteins. This high sequence disparity of Nsp2 among different PRRSV isolates
      suggested that it could be used as a marker to differentiate PRRSV genotypes. The
      5' RACE and primer extension analysis of three North American strains
      demonstrated that the utmost 5'-end nucleotides are conserved among PRRSV strains
      isolated from two continents. The predicted polyprotein 1 a/b contains conserved
      proteinase, polymerase and helicase domains responsible for polyprotein
      processing, RNA transcription and replication.

PMID- 10881676
TI  - Precursor genes of future pandemic influenza viruses are perpetuated in ducks
      nesting in Siberia.
AB  - Influenza A viruses of different subtypes were isolated from fecal samples of
      ducks in their nesting areas in Siberia in summer from 1996 to 1998. Phylogenetic
      analysis of the NP genes of the isolates in Siberia and those in Hokkaido, Japan
      on their flyway of migration from Siberia to the south in autumn revealed that
      they belong to the Eurasian lineage of avian influenza viruses. It is noted that
      the genes of the isolates in Siberia are closely related to those of H5N1
      influenza virus strains isolated from chickens and humans in Hong Kong in 1997 as
      well as to those of isolates from domestic birds in southern China. The results
      indicate that influenza viruses perpetuated in ducks nesting in Siberia should
      have contributed genes in the emergence of the H5N1 virus in Hong Kong. Vaccine
      prepared from avirulent A/duck/Hokkaido/4/96 (H5N3) influenza virus was potent
      enough to protect mice from challenge with lethal dose of the pathogenic H5N1
      virus [19]. Intensive surveillance study of aquatic birds especially in Siberia
      is, therefore, stressed to provide information on the future pandemic influenza
      virus strains and for vaccine preparation.

PMID- 10881677
TI  - Epitope mapping of the influenza A virus RNA polymerase PA using monoclonal
      antibodies.
AB  - To obtain reagents to functionally map the PA protein, we produced monoclonal
      antibodies specific to this protein. Twenty-two monoclonal antibodies reacting
      with PA protein in ELISA were divided into 10 groups on the basis of competitive
      binding patterns to this protein. Of these, seventeen monoclonal antibodies bound
      to PA polypeptide spanning amino acids 101-400 and three bound to that of amino
      acids 518-600, while the other two did not react with any PA polypeptides tested
      with the exception of full-length PA. Among these monoclonal antibodies, only
      five reacted with PA in A/PR/8/34 virus-infected cells in indirect
      immunofluorescence assay. Thus, we obtained monoclonal antibodies that recognize
      at least 10 distinct regions of the PA molecule. These monoclonal antibodies
      should be useful in dissecting functions of the PA protein.

PMID- 10881678
TI  - Extensive lymphopenia due to apoptosis of uninfected lymphocytes in acute measles
      patients.
AB  - Infection with measles virus induces a transient immunosuppression, which
      occasionally results in fatal opportunistic infections. To obtain fundamental
      information about the mechanism, we examined peripheral blood mononuclear cells
      (PBMC) from acute measles patients aged from infants to 35 years old, obtained at
      various times from incubation periods to 103 days after onset of rash, for the
      number of lymphocyte subsets by flowcytometry. The data were analyzed for
      relationships between aging of the patients and the severity of
      immunosuppression. In classical measles cases, infected lymphocytes detected as a
      minor population during the incubation period disappeared soon after onset of
      rash, whereas in the cases of serious illness, the infected cells persisted
      longer after the rash. At the onset of rash, remarkable lymphopenia had already
      occurred in all measles cases with reduction in cell numbers of CD4+ T cells,
      CD8+ T cells, B cells, neutrophils, and monocytes. In contrast, natural killer
      (NK) cells were increased in number and activated, which might be a response
      compensatory for the lymphopenia. Apoptosis-associated molecules such as
      CD95(Fas) and TNF-related apoptosis-inducing ligand-receptor (TRAIL-R) were
      highly expressed on the cell surface of most surviving non-infected lymphocytes,
      and DNA fragmentation was also observed upon incubation in vitro. These results
      suggested that the profound lymphopenia was primarily due to extended death of
      non-infected blood cells caused by apoptosis. The severity and duration of the
      lumphopenia were age-dependent; less severe in young children whereas much
      severer in infants under one year of age as well as adolescents and adults. From
      these results, it was suggested that remarkable lymphopenia due to apoptosis of
      uninfected cells is one of the principal causes for immunosuppression induced by
      measles virus infection, and is correlated with the age-dependent severity of the
      disease.

PMID- 10881679
TI  - Epitopes on glycoprotein E and on the glycoprotein E/glycoprotein I complex of
      bovine herpesvirus 1 are expressed by all of 222 isolates and 11 vaccine strains.
AB  - Glycoprotein E (gE) of bovine herpesvirus 1 (BHV1) forms a complex with
      glycoprotein I (gI) and plays an important role in cell-to-cell spread mechanisms
      of the virus, but is not essential for propagation of the virus. To study the
      antigenic variability of BHV1 glycoprotein E, a set of six well characterised
      monoclonal antibodies (MAbs) was established using BHV1 gE and gI deletion
      mutants, eukaryotically expressed gE and gI and pepscan analysis. Two of these
      MAbs reacted with a linear gE epitope (MAbs 3 and 52), two reacted with a more
      conformation dependent gE epitope (MAbs 61 and 81) and two reacted with epitopes
      formed by a complex formed between gE and glycoprotein I (MAbs 67 and 75). With
      these six MAbs the gE expression of 222 BHV1 isolates and 11 BHV1 modified-live
      vaccine strains was studied in vitro, using an immunoperoxidase monolayer assay.
      All 222 BHV1 isolates and 11 vaccine strains were found to react with MAbs 61, 81
      and 75. Three of the 222 isolates failed to react with MAb 67 and two of the
      vaccines reacted very weakly with MAbs 3 and 52. Analysis of the gE genes of
      these five aberrant isolates and the gE glycoproteins they expressed, did not
      show obvious size differences compared to wild-type BHV1. We conclude that the
      tested gE epitopes are highly conserved, including the epitopes formed by the
      gI/gE complex.

PMID- 10881680
TI  - Can HCV affect the efficacy of anti-HIV treatment?
AB  - To evaluate the impact of new antiretroviral combinations (HAART: Highly Active
      Anti Retroviral Therapy) on HCV replication and liver enzyme levels, we analysed
      the changes in HCV viremia and aminotransferase levels in HIV and HCV co-infected
      patients. Moreover, to evaluate the influence of HCV infection on the efficacy of
      HAART, we compared the virological, immunological and biochemical response to
      antiretroviral combinations in anti-HIV positive subjects with or without HCV
      infection. We enrolled eight consecutive outpatients with HIV-HCV coinfection and
      with indications for HAART (Group A). For each patient in group A, we selected an
      anti-HIV negative patient with indications for HAART, pair-matched for age, sex,
      risk factor for HIV infection, presumed duration of infection, number of CD4
      cells, HIV viremia and treatment schedule (Group B). A statistically significant
      increase in CD4 in both groups was found at 1st, 3rd and 6th month of
      antiretroviral therapy. A decrease in HIV-RNA in both groups was observed at 1st
      and 6th month of treatment. The percentage of patients with undetectable HIV-RNA
      at the 1st month was higher in Group B than in Group A (8/8 vs. 3/8, p = 0.025).
      Basal HCV-RNA viremia was very high in each case and no variations during
      treatment were observed. During therapy the aminotransferase levels slightly
      decreased in Group A and consistently increased in Group B. In Group A the
      differences were not significant to the statistical analysis; in Group B the
      aminotransferase levels at 3rd and 6th month were significantly higher than those
      observed at the baseline.

PMID- 10881681
TI  - Identification and in vivo expression of a prokaryotic-like ribosome recognition
      sequence upstream of the coat protein gene of potato virus X.
AB  - Conserved prokaryotic sequence motifs, distinct from the classic Shine-Dalgarno
      sequence, yet possessing homology to 16S rRNA in E. coli have been identified in
      a number of plant viruses. In this report, a similar Shine-Dalgarno-like motif
      located immediately upstream to the CP gene of potato virus X (PVX) was
      demonstrated to enable expression of a reporter gene in E. coli to approximately
      one third the level of a similar construct containing the classical Shine
      Dalgarno sequence. Both PVX-specific CP and RNA transcripts were detected in
      chloroplasts purified from transgenic potato plants containing the PVX CP gene
      and corresponding leader sequence. Protoplasts generated from these transgenic
      plants were used to demonstrate that expression of the PVX CP from chloroplasts
      is possible. The implications of these results on the PVX infection cycle are
      discussed.

PMID- 10881683
TI  - Molecular evolution of HCV genotype 2c persistent infection following mother-to
      infant transmission.
AB  - The molecular evolution of HCV 2c in a case of vertical transmission was studied
      by comparing the virus quasispecies in the sera from the mother and from the
      child in a two-year follow-up. The positivity of HCV-RNA since the delivery
      accounted for an in-utero infection. The Core-E1 genome region (nt 928-1225) was
      amplified by polymerase chain reaction (PCR) from serum samples collected at
      delivery and at 3, 9, 18 and 24 months after birth. The RIBA pattern was
      characterised by isolated anti-c22 positivity in the serum from mother and in
      sera from the child during the first 9 months. Additional presence of anti-c33
      was observed afterwards. Genetic relatedness among isolates and with a mother
      minor variant serum (Mo1. 13) was found (mean variability ranged between 0.79%
      and 1.20%). From phylogenetic analysis this variant was identified as the origin
      of one of the two main lineages that included all isolates from child sera at 9,
      18 and 24 months. The variability analysis has shown that high viral
      heterogeneity is present in the child serum collected at birth (3.16%). In this
      phase the dn/ds index (1.26%) indicates the presence of strong selective
      pressures. The development of child specific immune response at 9th month was
      concurrent with the disappearance of two mutants at positions 11 and 104 of E1.
      This rare case of in-utero mother-to-infant transmission can be considered as a
      model to elucidate the HCV quasispecies diversification during the first stage of
      infection.

PMID- 10881684
TI  - Identification of a new human DNA virus (TTV-like mini virus, TLMV)
      intermediately related to TT virus and chicken anemia virus.
AB  - TT virus (TTV) is the only known human virus with single-stranded circular DNA,
      with a possible but yet unclear relationship to chicken anemia virus (CAV) of the
      family Circoviridae. Here we report a new human virus resembling TTV and CAV,
      designated TTV-like mini virus (TLMV). This non-enveloped virus was smaller (< 30
      nm) but had a similar density (1.31-1.34 g/ml in CsCl) to TTV, when a TLMV/TTV
      coinfected plasma was analyzed. Full-length sequencing revealed that the TLMV
      genome was a circular DNA comprising 2860 nt (isolate CBD231); significantly
      shorter than TTV (TA278, 3852 nt) but longer than CAV (CAECUX1, 2319 nt). A
      strand-specific hybridization assay using oligonucleotide-coated beads suggested
      TLMV was negative-stranded, like TTV and CAV. In genomic organization, TLMV was
      similar to both TTV and CAV. The untranslated region of TLMV resembled CAV in
      that both had direct repeats, whereas the sequence homology was more evident
      between TLMV and TTV. The predicted ORF1 protein of TLMV was rich in R/W/F
      residues at its amino terminus; the richness in W was shared by TTV, F by CAV,
      and R by both. ORF2 proteins of the three viruses had a common motif,
      WX7HX3CXCX5H. Thus, TLMV is an intermediate between the remotely related TTV and
      CAV. Since CAV differs much from other circoviruses, it may better be classified
      together with TTV and TLMV under a new family: we would coin the
      Paracircoviridae.

PMID- 10881685
TI  - Nucleotide sequence and genome organisation of cherry mottle leaf virus and its
      relationship to members of the Trichovirus genus.
AB  - The nucleotide sequence of cherry mottle leaf virus (CMLV) was determined and
      compared to sequences of a number of plant viruses including the type member of
      the Trichovirus genus (apple chlorotic leafspot virus, ACLSV), and members of the
      Vitivirus genus including grapevine virus B, (GVB). The CMLV genome was
      determined to consist of 8003 nt excluding the poly(A) tail at the 3' end of the
      genome. The overall A + U content of CMLV genomic RNA was 59.1%, which is similar
      to ACLSV, but significantly different from GVB. Four putative open reading frames
      were identified (ORFs 1, 2, 3, and 4) encoding proteins of M(r) 215.8 kDa, 47
      kDa, 21.6 kDa, and 15.3 kDa, respectively. This differs from ACLSV which has 3
      ORFS, and GVB which has 5 ORFs. Protein database searches showed no matches of
      CMLV ORF4 with ACLSV sequences, but found similarities between ORF4 of CMLV and
      ORF5 of GVB, suggesting that this may be a nucleic acid-binding protein. CMLV and
      ACLSV formed a common virus clade in phylogenetic analysis of the coat protein
      amino acid sequence and except for CMLV's ORF4, these viruses show high levels of
      similarity throughout the genome. CMLV appears to be a member of the Trichovirus
      genus.

PMID- 10881686
TI  - Molecular evidence that sugarcane yellow leaf virus (ScYLV) is a member of the
      Luteoviridae family.
AB  - A previously uncharacterized virus was reported in southeast Brazil causing a
      yellowing leaf disease in sugarcane. The virus, termed sugarcane yellow leaf
      virus (ScYLV), shares features typical of the luteoviruses. To start the
      molecular characterization of ScYLV, the nucleotide sequence of the coat protein
      (CP), 17 kDa protein and C-terminus of the RNA-dependent RNA polymerase coding
      regions was determined from an RT-PCR amplification product. Comparisons showed
      that the deduced amino acid sequences share a considerable degree of identity and
      similarity with corresponding sequences of known luteoviruses, thus clearly
      establishing ScYLV as a member of the family Luteoviridae. The authenticity of
      the CP open reading frame was confirmed by its expression in Escherichia coli.
      The recombinant CP positively reacted in immunoblot assays with polyclonal
      antibodies raised against native ScYLV. Furthermore, phylogenetic analyses also
      suggest that the 5' and 3' coding blocks of the ScYLV genome possess different
      taxonomic affinities within the Luteoviridae family, as does also the genome of
      soybean dwarf virus.

PMID- 10881687
TI  - Comparison of proviral accessory genes between long-term nonprogressors and
      progressors of human immunodeficiency virus type 1 infection.
AB  - We compared proviral accessory gene sequences (nef, vpu, vpr, vif, rev, tat) of
      human immunodeficiency virus type 1 (HIV-1) in the peripheral blood mononuclear
      cells (PBMC) between seven long-term non-progressors (LTNP) and seven
      progressors. LTNP frequently harbored proviruses with mutated accessory genes,
      while almost all accessory genes were intact in progressors. Presence of
      quasispecies in attenuated viruses suggests that they were not just a fossil
      record of nonreplication proviruses. These attenuated viruses in LTNP may be the
      source of their strong immune response against HIV-1. Our result might have
      relevance to a design of potent therapeutic vaccines.

PMID- 10881688
TI  - Serological evidence of adenovirus infection in cats.
AB  - The widespread presence of adenoviruses in various species makes it probable that
      infection and the carrier state also exist in cats. On the basis of these
      considerations, investigations were carried out to find antibodies against
      adenovirus in sera from different cat populations kept under different
      conditions. For the antibody detection, purified adenovirus was used in an
      indirect ELISA. To produce positive serum, SPF cats were immunized with a
      purified hexon preparation. Altogether 632 field sera of different origin were
      tested. Among field samples, adenovirus seropositivity varied between 10-26%.

PMID- 10881689
TI  - Phylogenetic studies of tospoviruses (family: Bunyaviridae) based on intergenic
      region sequences of small and medium genomic RNAs.
AB  - Analysis of the intergenic region (IGR) of S and M RNAs of tospoviruses (Family
      Bunyaviridae) indicated their heterogeneity both in length and sequence. In
      general, IGRs of M RNA were shorter in length compared to the IGRs of their
      respective S RNA species. Percent identity among the S RNA IGR sequences of
      distinct tospovirus species varied from 42 to 57%, whereas it was 79 to 99% among
      isolates of the same species. Similarly, when IGRs of M RNAs were compared, there
      was higher sequence identity among isolates of the same tospovirus species (84 to
      98%) than among distinct tospovirus species (46 to 59%). Percent nucleotide
      identities and maximum likelihood trees of IGR sequences of S and M RNAs
      indicated that their sequence divergence is similar to that of nucleocapsid gene
      at inter and intra-species levels. This is the first detailed sequence analysis
      of IGRs of S and M RNAs of known tospoviruses.

PMID- 10881690
TI  - Phylogenetic analysis of H7 haemagglutinin subtype influenza A viruses.
AB  - A 945 nucleotide region (bases 76-1020) of the HA1 part of the HA gene was
      obtained for 31 influenza viruses of H7 subtype isolated primarily from Europe,
      Asia and Australia over the last 20 years. These were analysed phylogenetically
      and compared with sequences of the same region from 23 H7 subtype viruses
      available in Genbank. The overall results showed two geographically distinct
      lineages of North American and Eurasian viruses with major sublineages of
      Australian, historical European and equine viruses. Genetically related
      sublineages and clades within these major groups appeared to reflect geographical
      and temporal parameters rather than being defined by host avian species. Viruses
      of high and low virulence shared the same phylogenetic branches, supporting the
      theory that virulent viruses are not maintained as a separate entity in
      waterfowl.

PMID- 10881691
TI  - Cancer vaccines: single-epitope anti-idiotype vaccine versus multiple-epitope
      antigen vaccine.
AB  - In this study, we compared the immunogenicity and tumor-protective activity of
      anti-idiotypic antibodies mimicking a single tumor-associated epitope and tumor
      associated antigen expressing multiple potentially immunogenic epitopes. We
      focused our study on the colorectal-carcinoma(CRC)-associated antigen GA733 (also
      known as CO17-1A/KS1-4/KSA/EpCAM). Monoclonal anti-idiotypic antibody (Ab2) BR3E4
      was produced against murine anti-CRC mAb CO17-1A (Ab1) in rats. Full-length
      native GA733 protein was isolated from human tumor cells, and the extracellular
      domain protein (GA733-2E) was isolated from supernatants of recombinant
      baculovirus-infected insect cells by immunoaffinity chromatography. The
      immunomodulatory activity of the Ab2 was compared with that of the antigen, both
      in rabbits and in mice. Mice, like humans but not rabbits, express a GA733
      antigen homologue on some of their normal tissues. Thus, these in vivo models
      allow the comparison of the immunogenicity of Ab2 and antigen in the presence
      (mice) and absence (rabbits) of normal tissue expression and immunological
      tolerance of the GA733 antigen homologue. In rabbits, aluminum-hydroxide(alum)
      precipitated native GA733 antigen was superior to alum-precipitated Ab2 in
      inducing specific humoral immunity. In mice, alum-precipitated recombinant GA733
      2E antigen, but not alum-precipitated Ab2, induced specific humoral immunity.
      However, when the Ab2 was administered to mice in Freund's complete adjuvant,
      specific humoral immune responses were elicited. Ab2 in complete Freund's
      adjuvant and GA733-2E in alum were compared for their capacity to induce antigen
      specific cellular immunity in mice. Whereas lymphoproliferative responses were
      obtained with the recombinant antigen only, delayed-type hypersensitivity
      responses were obtained with both recombinant antigen and Ab2, although these
      responses were lower than after antigen immunization. The recombinant antigen in
      alum did not protect mice against challenge with antigen-positive syngeneic
      murine CRC cells. Similar studies with Ab2 BR3E4 mimicking the CO17-1A epitope
      were not possible because the tumor cells do not express this epitope after
      transfection with the human GA733-2 cDNA. However, similar studies with Ab2
      mimicking the epitope defined by mAb GA733, which is expressed by the transfected
      tumor cells, indicated a lack of tumor-protective activity of this Ab2. In
      contrast, the full-length antigen expressed by recombinant adenovirus inhibited
      the growth of established tumors in mice. In conclusion, soluble antigen is a
      more potent modulator of humoral and cellular immune responses than Ab2, both
      administered in adjuvant. However, for induction of protective immunity, the
      immunogenicity of the antigen must be further enhanced, e.g., by expression of
      the antigen in a viral vector.

PMID- 10881692
TI  - Counterpoint. Cancer vaccines: single-epitope anti-idiotype vaccine versus
      multiple-epitope antigen vaccine.
AB  - Anti-idiotype (Id) vaccine therapy has been tested and shown to be effective, in
      several animal models, for triggering the immune system to induce specific and
      protective immunity against bacterial, viral and parasitic infections. The
      administration of anti-Id antibodies as surrogate tumor-associated antigens (TAA)
      also represents another potential application of the concept of the Id network.
      Limited experience in human trials using anti-Id to stimulate immunity against
      tumors has shown promising results. In this "counter-point" article, we discuss
      our own findings showing the potential of anti-Id antibody vaccines to be novel
      therapeutic approaches to various human cancers and also discuss where anti-Id
      vaccines may perform better than traditional multiple-epitope antigen vaccines.

PMID- 10881693
TI  - Immunohistochemical analysis of glioma-infiltrating leucocytes after peripheral
      therapeutic immunization with interferon-gamma-transfected glioma cells.
AB  - We have shown previously that rejection of preinduced rat brain tumours is
      possible following therapeutic immunizations with interferon-gamma (IFN gamma)
      transfected glioma cells (N32-IFN gamma). In the present study we have used the
      same model to evaluate whether quantitative differences in tumour-infiltrating
      lymphocytes can be detected between animals receiving therapeutic immunizations
      with either IFN gamma-transfected glioma cells, wild-type glioma cells or no
      treatment. Since leucocyte transpedesis into the tumour can be anticipated to
      depend on the state of vascularization, we have mapped the development of
      microvessels in the tumour in parallel with the leucocyte infiltration. Our
      results show that microvessels start to form at day 7 and then gradually increase
      in number and size, indicating the establishment of an extensive vascularization
      by day 24. Leucocyte infiltration displays a biphasic pattern after tumour
      grafting. We have therefore studied the infiltration kinetics after an early
      immunization (1 day after intracerebral isografting) and compared the effects
      with those of a late immunization (10 days after intracerebral isografting) with
      N32-IFN gamma or wild-type N32. Our results show (1) an early infiltration of
      granulocytes 3 days after isografting; (2) a T-cell-receptor-positive (TCR+) T
      cell infiltration starting on day 10; (3) a macrophage infiltration starting on
      day 13; (4) a CD8+ cell infiltration starting on day 13. The proportions of TCR+
      T cells, CD8+ cells and natural killer cells differs significantly between
      animals immunized with N32-IFN gamma and those receiving wild-type N32, when
      analysed 14 days after immunization at day 10. This difference can only be
      detected when animals are immunized at later stages of tumour growth. We propose
      that this could depend on an early-immunization-independent leucocyte
      infiltration during tumour establishment. This has to be considered when
      evaluating studies of leucocyte infiltration in experimental tumours.

PMID- 10881694
TI  - Presence of IgE antibodies to bovine serum albumin in a patient developing
      anaphylaxis after vaccination with human peptide-pulsed dendritic cells.
AB  - Dendritic cells are professional antigen-presenting cells that can be generated
      in vitro either from monocytes or from CD34+ peripheral blood progenitor cells by
      using recombinant cytokines. These cells have potential implications for
      immunotherapeutic approaches in the treatment of cancer and other diseases. We
      have conducted a phase I study in melanoma patients using peptide-pulsed
      dendritic cells cultured in medium supplemented with 10% fetal calf serum (FCS)
      and a cocktail of cytokines. Peptide-pulsed dendritic cells were injected
      intravenously at 2-week intervals. Here we report on a case of type I
      hypersensitivity anaphylactic reaction after repetitive vaccination with
      autologous peptide-pulsed cells. Pre-vaccination and post-vaccination serum
      samples were evaluated for the presence of antibodies to FCS and bovine serum
      albumin (BSA). A retrospective study in 7 patients vaccinated with FCS-cultured
      dendritic cells demonstrated the presence of IgG and IgM antibodies to FCS and
      BSA after vaccination in 6 out of 7 patients. However, IgE antibodies were absent
      in all patients with the exception of the patient developing anaphylaxis. The
      patient's serum was demonstrated to contain a strong IgE response directed
      against BSA. In contrast, 2 patients vaccinated with dendritic cells cultured
      under serum-free conditions developed no antibodies to FCS and BSA after
      repetitive vaccination. We suggest that patients can be sensitized with an IgE
      response against BSA leading to anaphylactic reactions. On the basis of these
      data, dendritic cells cultured in autologous serum or under serum-free conditions
      are recommended for therapeutic applications in vivo.

PMID- 10881695
TI  - Antitumor effect of heat-killed Lactobacillus plantarum L-137 through restoration
      of impaired interleukin-12 production in tumor-bearing mice.
AB  - We have previously reported that heat-killed Lactobacillus plantarum L-137 is a
      potent inducer of interleukin-12 (IL-12) in vivo as well as in vitro in mice. In
      order to develop effective usage of L. plantarum L-137 for tumor immunotherapy,
      we examined its antitumor effect against DBA/2 mice inoculated with syngenic
      P388D1 tumor cells in different treatment schedules. Daily injection of L.
      plantarum L-137 from the day of tumor inoculation induced a steep increase in
      plasma IL-12 only after the first injection but not after subsequent injections,
      and had no effect on tumor growth and survival time. In contrast, daily injection
      of L. plantarum L-137 from the 7th day after tumor inoculation exerted a marked
      antitumor effect but such an effect was not evident in mice treated with L.
      plantarum L-137 twice a week from the 7th day. IL-12 production was considerably
      impaired at the first injection but steeply increased after the third injection
      in the mice injected daily with L. plantarum L-137 from the 7th day. Our results
      suggest that daily administration of L. plantarum L-137 is required to exert an
      antitumor effect at the late stages of tumor development when IL-12 production is
      considerably impaired.

PMID- 10881696
TI  - Intracellular cytokine profile of T cells from children with acute lymphoblastic
      leukemia.
AB  - PURPOSE: During an ongoing immune response, cytokines produced by T helper types
      1 (Th1) and 2 (Th2) together with T cytotoxic types 1 (Tc1) and 2 (Tc2) are
      critical to the effectiveness of that response. Dysregulated expansion of one or
      the other subset may contribute to the impaired function of the T-cell-mediated
      immune system in cancer patients. In the present study we have investigated
      whether such dysregulation might exist in children with acute lymphoblastic
      leukemia (ALL). METHODS: We analyzed 61 blood samples from 45 children with B
      cell precursor ALL and 16 healthy children. Interleukin(IL)-2, IL-4, and
      interferon gamma (IFN gamma) production of their respective purified CD4+ and
      CD8+ T cells were assessed at the single-cell level by intracellular-cytokine
      staining flow cytometry. RESULTS: At the time of diagnosis, IL-2-producing cell
      populations in CD4+ and CD8+ T cells were reduced below the normal range in 31 of
      44 (70.5%) and 23 of 38 (60.5%) cases respectively. Similarly, IFN gamma
      producing cell populations in CD4+ and CD8+ T cells decreased in 17 of 44 (38.6%)
      and 18 of 38 (47.4%) cases respectively. Conversely cell populations capable of
      IL-4 production in CD4+ and CD8+ T cell subsets were increased in 13 of 30
      (43.3%) and 15 of 30 (50.0%) cases respectively. Therefore, the Th1-to-Th2 and
      Tc1-to-Tc2 ratios (1.6 +/- 2.2 and 7.7 +/- 6.7 respectively) were significantly
      lower in peripheral blood T cells of ALL patients (n = 30) than those (6.0 +/-
      2.9 and 20.1 +/- 10.3 respectively) in 15 healthy controls (P < 0.0001). Although
      both CD45RA+/CD4+ and CD45RA+/CD8+ cells significantly increased in 43 ALL
      patients (P < 0.05), there existed no apparent correlation between CD45 isoform
      expression and cytokine (IL-2 and IFN gamma) production. Interestingly, the
      ability to produce both IL-2 and IFN gamma was recovered in 8 cases examined,
      after complete remission had been achieved. CONCLUSION: These observations
      suggest that, in both CD4+ and CD8+ T cells of ALL patients, there is a
      dysregulation in the functionality of Th1 (Tc1) and Th2 (Tc2) cells with a gross
      reduction of Th1 (Tc1) cell populations and an expansion in Th2 (Tc2).

PMID- 10881697
TI  - Initiation of humoral and cellular immune responses in patients with refractory
      Hodgkin's disease by treatment with an anti-CD16/CD30 bispecific antibody.
AB  - Fifteen patients with refractory Hodgkin's disease were treated in a dose
      escalation trial with the bispecific monoclonal antibody (bi-mAb) HRS-3/A9, which
      is directed against the Fc gamma receptor III (CD16 antigen) and the Hodgkin's
      associated CD30 antigen. Treatment consisted of four cycles of four bi-mAb
      infusions given over 1 h every 3-4 days at different dose levels ranging from 1
      mg/m2 to 64 mg/m2. Measurable serum levels (above 0.1 microgram/ml) of
      circulating bi-mAb could be detected in patients treated with doses above 4
      mg/m2, reaching peak levels of 9.5 micrograms/ml immediately after the end of
      antibody infusion on the highest dose level. Bi-mAb elimination corresponded to
      second-order kinetics with a terminal half-life time (t1/2, beta) of 28-32 h. Bi
      mAb treatment induced the occurrence of human anti-(mouse Ig) antibodies (HAMA)
      in 6 out of 13 patients initially testing negative. All 6 patients not only
      developed anti-isotypic anti-(mouse Ig) but also anti-idiotypic and anti-anti
      idiotypic antibodies. While no consistent changes of peripheral blood cell
      counts, or of any lymphocyte subpopulation including natural killer (NK) cells,
      has been observed, 4 out of 6 evaluable patients treated with doses of at least 4
      mg/m2 showed an increase of NK cell activity within 2 weeks after treatment,
      which lasted for a maximum of 12 weeks. Circulating amounts of soluble CD30
      antigen could be detected in the serum of 6 patients. However, like the results
      and time courses of all the other immunological parameters evaluated, this was
      not predictive for treatment outcome.

PMID- 10881698
TI  - DNA scission in hamster cells and isolated nuclei studied by low-voltage electron
      beam irradiation.

PMID- 10881700
TI  - The effects of ionizing radiation on the kinetics of DNA replication in
      synchronized Chinese hamster ovary cells.

PMID- 10881699
TI  - Chloroquine: nonselective inhibition of recovery from radiation injury in tumors
      and normal tissues.

PMID- 10881702
TI  - Effects of caffeine on radiation-induced mitotic inhibition in S-180 ascites
      tumor cells.

PMID- 10881701
TI  - Distribution and toxicity of monomeric and polymeric 239Pu in immature and adult
      rats.

PMID- 10881703
TI  - Laser irradiation induces increased activity of liver elongation factor 1.

PMID- 10881704
TI  - Electron affinic sensitization. V. Radiosensitization of hypoxic bacteria and
      mammalian cells in vitro by some nitroimidazoles and nitropyrazoles.

PMID- 10881705
TI  - Hypoxic cell radiosensitizers: comparative tests of some electron affinic
      compounds using epidermal cell survival in vivo.

PMID- 10881706
TI  - Toxicity of 144Ce inhaled as 144CeCl3 by the beagle: metabolism and dosimetry.

PMID- 10881707
TI  - Repair of radiation-induced DNA breaks in human adenovirus.

PMID- 10881708
TI  - Chromosome aberrations in the leukocytes of partial-body- and whole-body
      irradiated swine.

PMID- 10881709
TI  - Effects of X-irradiation on DNA precursor metabolism and deoxyribonucleoside
      triphosphate pools in Chinese hamster cells.

PMID- 10881710
TI  - Initial studies with a line of radioresistant rat tumor cells.

PMID- 10881711
TI  - Specificity of radioprotective and cytotoxic effects of cysteamine in HeLa S3
      cells: generation of peroxide as the mechanism of paradoxical toxicity.

PMID- 10881712
TI  - Cosmic radiation at high altitudes and U.S. cancer mortality, 1950-1969.

PMID- 10881713
TI  - Effects of radiation on bone formation: a functional assessment.

PMID- 10881714
TI  - Effect of X-radiation on the DNA-membrane complex from Escherichia coli.

PMID- 10881715
TI  - Recovery from radiation-carcinogenic injury to the mouse ovary.

PMID- 10881717
TI  - Repair of sublethal damage and oxygen enhancement ratio for low-voltage electron
      beam irradiation.

PMID- 10881716
TI  - Radiation sensitization of Micrococcus radiodurans by postirradiation incubation
      at nonpermissive temperature.

PMID- 10881718
TI  - Calculations related to the possible use of photons, neutrons, negatively charged
      pions, protons, and alpha particles in radiotherapy.

PMID- 10881719
TI  - Free radicals in gamma-irradiated frozen solutions of deoxyadenosine-5'
      monophosphate. A computer analysis of temperature-dependent ESR spectra.

PMID- 10881720
TI  - Inactivation of ribonuclease S-peptide by the primary aqueous radicals.

PMID- 10881721
TI  - Reactions of phenylalanine derivatives, methionine derivatives, and their
      mixtures in aqueous solution with pulse-radiolytically generated H atoms.

PMID- 10881722
TI  - Superoxide dismutase inactivation by radiation-induced radicals: evidence for
      histidine residues in the active site.

PMID- 10881723
TI  - Symptoms of X-ray damage to radiosensitive mouse leukemic cells: asynchronous
      populations.

PMID- 10881724
TI  - RBE and OER variations of mixtures of plutonium alpha particles and X-rays for
      damage to human kidney cells (T-1).

PMID- 10881725
TI  - Chromosome aberrations and T-cell survival in human lymphocytes.

PMID- 10881726
TI  - A comparison of the effectiveness of NF-167 and metronidazole as hypoxic cell
      sensitizers of KHT tumor cells in vitro.

PMID- 10881727
TI  - Inhibition of radiation-induced lymphatic leukemia in C57BL mice by 19S alpha-2
      globulin (alpha 2-MG) from human blood serum.

PMID- 10881728
TI  - Changes in electrophoretic mobility of cultured cells after X-irradiation and
      their modification by SH-blocking agents and hemagglutinin.

PMID- 10881729
TI  - Persistence of radiation-induced chromosome aberrations in marmoset and man.

PMID- 10881730
TI  - Kinetics of the skeletal retention of 239Pu(IV).

PMID- 10881731
TI  - A note on survival curves with shoulders.

PMID- 10881732
TI  - Comparative mating ability of gamma sterilized and normal fruit flies, Dacus
      zonatus.

PMID- 10881733
TI  - Serous tumors of low malignant potential of the ovary. 1. Diagnostic pathology.
AB  - Serous ovarian tumors of low malignant potential (SLMP)--also called borderline
      tumors of the ovary--represent a heterogeneous group of ovarian epithelial
      neoplasms. In general, this tumor type has a favorable prognosis. Nevertheless,
      10-20% of SLMP exhibit a progressively worsening clinical course, with widespread
      peritoneal implants and death of the patient within 5 years. The criteria for
      recognizing the SLMP with an unfavorable prognosis and for distinguishing SLMP
      from highly differentiated ovarian carcinomas are summarized in this report. The
      importance of supporting methods, e.g., DNA cytophotometry, is demonstrated,
      revealing that in most cases aneuploidy can be regarded as an indicator for
      aggressiveness of the tumor and for poor clinical outcome. The importance of the
      new concept of micropapillary serous carcinomas (MPSC), the relationship of this
      variant of SLMP to invasive serous carcinomas, and the prognostic importance of
      invasive vs noninvasive peritoneal implants are discussed. (The concepts of
      molecular pathology of SLMP will be discussed in part 2 of this serial paper.)

PMID- 10881734
TI  - Kinetic profiles of intraepithelial and invasive prostatic neoplasias: the key
      role of down-regulated apoptosis in tumor progression.
AB  - The cell kinetic of prostatic intraepithelial neoplasia (PIN) is poorly
      understood. Herein we report the kinetic pattern of PIN, both not associated
      (primary) and associated (secondary) with coexistent invasive carcinoma (PCa).
      Surgical specimens collected in 20 cases of primary PIN, 20 of secondary PIN and
      20 of PCa were studied by MIB-1 immunostaining, in situ end-labeling (ISEL) and
      DNA histogram analysis, and the cell density in each case was estimated using the
      formula N = (n pi/4)2. Fifty high-power fields (HPF), or the complete lesion if
      smaller, were screened in each lesion, and both mean and standard deviation were
      recorded. Statistical differences were studied by means of Fisher's exact test.
      ISEL indices were significantly (P < 0.0001) lower in PCa (0.1 +/- 0.3) than in
      primary PIN (0.5 +/- 0.3), while the MIB-I indices were similar in both
      conditions (P = 0.56). Statistically significant differences were also detected
      for both MIB-1 and ISEL indices when secondary PIN (MIB-1 1.9 +/- 0.7, ISEL 3.7
      +/- 3.3) was compared with primary PIN (MIB-1 2.5 +/- 2.1, ISEL 0.5 +/- 0.3) and
      PCa (P < 0.0001). In terms of cellularity, primary PIN (26.3 +/- 7.1) revealed
      scores significantly lower (P < 0.0001) than those recorded in PCa (39.0 +/- 8.8)
      and secondary PIN (32.9 +/- 14.3). In conclusion, early prostatic tumor is mainly
      defined by down-regulated apoptosis rather than by increased proliferation.
      Secondary PIN displays unique kinetic features suggesting an evolved stage of
      primary PIN.

PMID- 10881735
TI  - Mammographically detected in situ lobular carcinomas of the breast.
AB  - We present ten cases of mammographically detected lobular carcinoma in situ
      (LCIS), involving a single area of variable size (up to a quadrant) in seven
      cases and the entire gland in three cases. Histologically, calcifications were
      associated with necrotic central areas within the in situ carcinomatous foci.
      Multiple foci of LCIS were observed in all five cases in which mastectomy had
      been performed. Cytologically, the lesions were characterized by a solid
      proliferation of round noncohesive cells with nuclei of intermediate size.
      Immunocytochemically, all cases were E-cadherin and p53 negative, and c-ErbB-2,
      GCDFP-15 and estrogen receptor positive. The proliferation index, evaluated with
      Ki67, was in the low range. Four cases were associated with foci of infiltrating
      lobular carcinoma (ILC). These findings contradict the commonly held opinion that
      LCIS is not mammographically detectable because of its lack of necrosis and
      calcification. This study documents the existence of a variant of LCIS exhibiting
      the mammographic features and central necrosis classically associated with ductal
      carcinoma in situ (DCIS), while retaining the spatial distribution, cytological
      composition and immunocytochemical features of lobular carcinoma.

PMID- 10881737
TI  - Highly sensitive diagnosis of amyloid and various amyloid syndromes using Congo
      red fluorescence.
AB  - In order to find how best to diagnose amyloid deposits as early as possible, the
      sensitivity of three different methods that can be applied to the diagnosis of
      amyloid in tissue sections have been compared: the Congo red staining method
      (CR), the combination of CR and immunocytochemistry (CRIC) and Congo red
      fluorescence (CRF). Tissue blocks were available from 25 patients, including 11
      with immunohistochemically distinct and 3 with chemically undefined amyloid
      diseases. The results revealed (a) that CRF is more sensitive than either CR or
      CRIC, as shown qualitatively and quantitatively, (b) that CRF can therefore be
      utilized to track down even minute amyloid deposits, which can be missed by the
      other two methods; (c) that the specificity of CRF and CRIC is secured on double
      stained sections by the demonstration of green birefringence (GB) of the CRF
      marked and IC-marked areas; (d) that CRF can be performed on the spot by just
      changing the light source; and (e) that CRF is not hampered by the congruent IC
      chromogen overlay, which ensures the specific classification of the amyloid
      deposits as applied to different amyloid classes. In conclusion, CRF was
      demonstrated to be the most sensitive method for direct diagnosis of amyloid in
      tissue sections. This method can, therefore, allow the earliest diagnosis and
      classification of amyloid, which is a good basis for an amyloid class-specific
      therapy while organ damage is still minimal.

PMID- 10881736
TI  - Bio-morphological events in the development of the human female mammary gland
      from fetal age to puberty.
AB  - Bio-morphological understanding of the developing human mammary glands may
      clarify some aspects of breast pathology, including cancer. In particular, some
      epidemiological data suggests that during fetal growth an altered intrauterine
      hormonal status, especially a change in estrogen status, could predispose to
      carcinogenesis. In an attempt to achieve new information on early breast growth,
      a series of developing human breasts have been analyzed, namely: 4 fetal breasts
      (28-32 weeks of gestational age), 7 infant breasts (7 h to 2 years) and 1 puberal
      breast (12 years). In addition to the morphological features, we studied the
      immunohistochemical expression of some markers involved in morphogenesis, such as
      MIB-1 for cell proliferation, bcl-2 for apoptosis control, CD34 for
      vasculogenesis, estrogen (ER) and progesterone (PR) receptors for hormonal
      profile, and smooth-muscle actin for myoepithelial differentiation. The results
      were as follows: (a) lobules, absent between 28 weeks and 2 days, were well
      evident at 2 years of age and at puberty; (b) myoepithelial cells appeared from
      28 weeks onward and persisted later with no modification in quantity and
      distribution; (c) epithelial cell proliferation was constantly low; (d) in all
      breasts inner epithelial cells showed diffuse bcl-2 positivity, while basal
      myoepithelial-like cells were generally negative; (e) all breasts were well
      vascularized with two different patterns: periductal vascularization (PDV) and
      interductal vascularization (IDV), IDV being always present, whereas PDV was
      found only in infant breasts; (f) ER and PR were almost absent in fetal and
      infant breasts, while their expression was high in the epithelial cells of the
      puberal breast; (g) stromal cells had no hormonal receptors and were
      heterogeneous for proliferation and bcl-2 expression. Interestingly, two fetal
      breasts showed high proliferation and high ER expression, respectively, in their
      epithelial compartment. This could be the expression of an altered hormonal
      environment in utero, representing a basis for possible subsequent cancer
      initiation.

PMID- 10881738
TI  - Mig, GRO alpha and RANTES messenger RNA expression in lining layer, infiltrates
      and different leucocyte populations of synovial tissue from patients with
      rheumatoid arthritis, psoriatic arthritis and osteoarthritis.
AB  - To investigate lymphocyte and monocyte recruitment-specific chemokine expression
      in synovial tissues from patients with rheumatoid arthritis (RA), psoriatic
      arthritis (PA) and osteoarthritis (OA), synovial membranes and cytocentrifuge
      preparations of 7 RA, 8 PA and 10 OA patients were examined by in situ
      hybridisation with antisense probes of Mig, GRO alpha and RANTES and by
      immunohistochemistry. Patients' local disease activity (swelling and tenderness)
      in order to was graded and histological evaluation was performed compare these
      data with their chemokine expression profiles. Mig and RANTES hybridisation
      signals were detected in the synovial lining layer and in cellular infiltrates,
      whereas GRO alpha expression was localised exclusively in the lining layer of PA
      and RA. Cytological analysis revealed Mig and GRO alpha mRNA mainly in monocytic
      cells expressing KIM6, while RANTES mRNA was demonstrated predominantly in
      lymphocytic cells expressing CD3. In OA synovial membranes, significantly fewer
      hybridisation signals were present than in RA and PA synovial membranes. Patients
      with PA and RA had mild to severe local disease activity, whereas OA patients
      showed only mild disease activity. Histologically, PA and RA inflammatory scores
      ranged from 1 to 5, while OA synovium was consistently graded 1. Therefore, we
      conclude that the differential expression of Mig, GRO alpha and RANTES in
      resident and in inflammatory cells has an important role in regulating leucocyte
      traffic in inflammatory arthropathies. The diverse leucocyte specificity of Mig,
      GRO alpha and RANTES may thus regulate the recruitment of different leucocyte
      populations, as detected in PA and RA. Therefore, the pattern of cellular
      infiltration in human synovitis and the corresponding clinical signs of
      inflammation basically reflect the localisation and expression intensity of
      chemokines, which may be an important target for future disease modulation.

PMID- 10881739
TI  - Hepatic peroxisomes in isolated hyperpipecolic acidaemia: evidence supporting its
      classification as a single peroxisomal enzyme deficiency.
AB  - Hyperpipecolic acidaemia is still regarded as a peroxisomal assembly deficiency.
      The enzyme responsible for the accumulation of pipecolic acid is located in the
      peroxisomes in man. We studied the appearance and alterations of peroxisomes in
      liver biopsy material from three unrelated children suffering from isolated
      hyperpipecolic acidaemia, in which only the metabolism of pipecolic acid is
      disturbed, using light and electron microscopy after cytochemical staining for
      visualisation of peroxisomes. Morphometric results showed the presence of normal
      sized to small peroxisomes, an increase in number and abnormally shaped
      organelles, suggesting enhancement of metabolic efficiency. In one case enlarged
      organelles were observed. Skin fibroblasts were studied in all patients: their
      peroxisomes appeared to be normal. The obvious presence of peroxisomes in
      isolated HPA indicates that this disorder should be classified as a single
      peroxisomal enzyme deficiency.

PMID- 10881740
TI  - The pattern of prion-related protein expression in the gastrointestinal tract.
AB  - Prion diseases or transmissible spongiform encephalopathies have been shown to be
      communicated by oral ingestion of the infectious agent. However, the exact route
      of transmission is still unknown. In order to better understand the
      pathophysiology of these diseases, it is crucial to identify cell types of
      peripheral tissues in which the infectious agent may propagate. Since expression
      of cellular prion protein (PrPc) is a prerequisite for prion replication, we
      determined the expression of PrPc in the mucosa of the gastrointestinal tract
      using immunohistochemistry. Expression of PrPc was negative or weak in the neck
      region of the gastric mucosa and moderate to strong in crypts of both the small
      and the large bowel. PrPc was found to be upregulated in the mucosa of patients
      with Helicobacter pylori gastritis. In contrast, PrPc staining appeared to be
      downregulated in patients with inflammatory disorders of the large bowel and it
      remained moderate to strong in inflammatory disorders of the small bowel. Our
      results support the notion that epithelial cells of the gastrointestinal tract
      may represent a possible target for prion entry and replication.

PMID- 10881741
TI  - Solid-pseudopapillary tumor of the pancreas: its origin revisited.
AB  - Solid-pseudopapillary tumor of the pancreas (SPT) has distinctive morphologic and
      biologic features but an unclear origin. It is classified among the pancreatic
      epithelial tumors, though many are reported to be negative for cytokeratin. Also
      unclear are its neuroendocrine differentiation, its capability to express alpha-1
      antitrypsin (AAT) and, in view of the tumor's striking prevalence in women, its
      relationship with the female genital tract. To clarify these issues, the
      immunoprofiles of 59 SPTs were defined by applying a battery of antibodies
      against cytokeratin, vimentin, neuron-specific enolase (NSE), synaptophysin,
      chromogranin A, tyrosine hydroxylase (TH), AAT, LeuM1, Ki-M1P, smooth-muscle
      actin, CD34, alpha-inhibin, calretinin, placental alkaline phosphatase (PLAP),
      and progesterone and estrogen receptors. The most consistent markers with the
      strongest immunoreactivity were vimentin, AAT, NSE, and the progesterone
      receptor, which were each found in more than 90% of the tumors. Using
      immunocytochemical methods involving antigen retrieval, cytokeratin was
      demonstrated in almost 70% of the cases. Synaptophysin was found in 22% of the
      tumors, while chromogranin was absent and tyrosine hydroxylase was only present
      in a few tumors. None of the other markers tested were expressed by SPTs. This
      staining pattern fails to reveal a clear phenotypic relationship with any of the
      defined cell lineages of the pancreas. In view of the striking female
      preponderance of SPTs and the known close approximation of the genital ridges to
      the pancreatic anlage during embryogenesis, it is, however, hypothesized that
      SPTs might derive from genital ridge/ovarian anlage-related cells, which were
      attached to the pancreatic tissue during early embryogenesis.

PMID- 10881742
TI  - Adult hyperinsulinemic hypoglycemia not caused by an insulinoma: a report of two
      cases.
AB  - Nesidioblastosis is rare in adults and accounts for 0.5-5% of cases of organic
      hyperinsulinemia. The diagnosis of nesidioblastosis should be considered when
      peroperative imaging modalities fail to localize a lesion in patients with
      hyperinsulinism. Two female patients, aged 55 and 16 years, with hyperinsulinemic
      hypoglycemia are reported. Somatostatin receptor scintigraphy showed slight focal
      activity in both patients. The first patient underwent a Whipple procedure and
      became diabetic. The second patient underwent a distal hemi-pancreatectomy and
      suffered from recurrent hypoglycemic episodes 3 months after surgery, for which
      she is presently being treated with octreotide. Histological examination of the
      resected pancreata revealed focally increased islet tissue and a number of
      slightly hypertrophic beta cells. Such histological abnormalities have been
      related to functional changes of beta-cells. In infantile nesidioblastosis, a
      proportion of cases has been associated with mutations in one of several genes.
      Whether such mutations, leading to hyperinsulinism, also play a role in adult
      nesidioblastosis is presently unknown.

PMID- 10881743
TI  - Allelic losses on chromosome arm 10q and mutation of the PTEN (MMAC1) tumour
      suppressor gene in primary and metastatic malignant melanomas.
AB  - Malignant melanomas frequently show loss of alleles on the long arm of chromosome
      10. The PTEN (MMAC1) gene has been identified as a tumour suppressor gene at
      10q23.3 that is mutated in various types of advanced human cancers. We have
      investigated a series of 40 sporadic melanomas from 37 patients (15 primary
      cutaneous melanomas and 25 melanoma metastases) for allelic losses on chromosome
      10, as well as for deletion and mutation of the PTEN gene. Microsatellite
      analysis revealed loss of heterozygosity at loci located on 10q in tumours from
      15 of 34 patients investigated (44%). Somatic PTEN mutations were identified in
      melanomas from 4 of 37 patients (11%), all of whom had metastatic disease. In two
      of these patients, the tumours had additionally lost one PTEN allele, indicating
      complete loss of wild-type PTEN in the tumour cells. Our findings corroborate
      that loss of heterozygosity on chromosome 10 is a frequent aberration in
      malignant melanomas and implicate PTEN as a tumour suppressor gene inactivated by
      somatic mutation in a fraction of these tumours.

PMID- 10881744
TI  - Mutation of p53 with loss of heterozygosity in the osteosarcomatous component of
      a dedifferentiated chondrosarcoma.
AB  - We investigated a dedifferentiated chondrosarcoma of a 61-year-old woman with an
      osteosarcomatous high-grade component for p53 alteration. The low-grade
      cartilaginous and the high-grade osteosarcomatous components of the tumor were
      macrodissected and evaluated separately by immunohistochemistry and molecular
      biology. We used PCR-SSCP analysis and direct sequencing to screen exons 4-8 for
      p53 mutations. The p53 intron 1-polymorphism was investigated for loss of
      heterozygosity. A functionally relevant p53 missense mutation in codon 193 of
      exon 6 (A-to-T transversion) with loss of wild-type allele was detected only in
      the dedifferentiated component. Using the monoclonal antibody DO-1,
      immunohistochemistry failed to show p53 overexpression. This evidence of p53
      mutation may be regarded as at least a co-factor that "switched" the preexisting
      low-grade conventional chondrosarcoma to a highly malignant dedifferentiated
      tumor.

PMID- 10881745
TI  - Heterotopic thyroid tissue at the porta hepatis in a fetus with trisomy 18.
AB  - Heterotopic thyroid tissue at the porta hepatis in a fetus with trisomy 18 is
      described. The fetus had an eutopic thyroid gland without any abnormalities. The
      heterotopic thyroid was found at the porta hepatis and showed histological
      features similar to the eutopic thyroid. Immunohistochemically, the heterotopic
      follicles were positive for thyroglobulin, but no calcitonin-positive cells were
      found. Intra-abdominal heterotopic thyroid is exceedingly rare in locations other
      than the ovary, and to our knowledge, this is the first report of a fetal case.
      The present case provides clear evidence that abdominal heterotopic thyroid can
      occur as a congenital anomaly. Migration abnormality of the median anlage of the
      thyroid is the most likely histogenesis of heterotopic thyroid at the porta
      hepatis.

PMID- 10881746
TI  - Primary lumbosacral Wilms tumour associated with occult spinal dysraphism.
AB  - A 4-year-old child presenting with sudden-onset paraplegia and a sacral tumour in
      association with spina bifida occulta is reported. There were no stigmata of
      spinal dysraphism at birth. Imaging studies confirmed a sacral tumour with
      extradural extension up to T10 and spinal dysraphism. The histological features
      of the extradural and sacral components of the tumour were consistent with a
      Wilms tumour. The differential diagnosis included a primary sacral teratoma
      containing Wilms tumour elements or a primary extrarenal Wilms tumour arising in
      association with a spinal dysraphism. There was no clinical response to
      chemotherapy or radiotherapy.

PMID- 10881747
TI  - Optical recording of impulse propagation in designer cultures. Cardiac tissue
      architectures inducing ultra-slow conduction.
AB  - It has long been established that slow conduction constitutes one of the key
      mechanisms in the generation of cardiac arrhythmias. Also, it has been recognized
      that alterations in the cellular architecture of cardiac tissue can contribute to
      slow conduction. Based on the recent development of an experimental system
      permitting both the design of geometrically defined cardiac tissue structures in
      culture and the measurement of impulse propagation at the cellular level, we
      investigated the extent of conduction slowing along a tissue structure consisting
      of a cell strand releasing multiple side branches. This structure, which can
      functionally be looked upon as a series of interconnected current-to-load
      mismatches, gave rise to ultra-slow conduction (1-2 cm/s) that displayed a high
      margin of safety due to a "pull" and "push" effect exerted by the side branches
      on electrotonic current flow along the main strand. Under physiological
      conditions, such branching structures might contribute to slow conduction in the
      AV-node and, under pathophysiological conditions, to the precipitation of
      reentrant arrhythmias within minuscule tissue regions in a structurally remodeled
      myocardium. The results illustrate that the combination of patterned growth
      techniques and optical recording of transmembrane voltage are ideally suited to
      characterize systematically the relationship between tissue structure and impulse
      conduction.

PMID- 10881748
TI  - Mechanism of cardiac fibrosis by angiotensin. New insight revealed by genetic
      engineering.
AB  - Accumulating data show that excess of angiotensin II (Ang II) is involved in
      cardiac fibrosis. Many experimental studies suggested that Ang II induces cardiac
      fibrosis not by its blood pressure-raising action, but rather by a direct action
      on the heart. However, it has been difficult to distinguish the local and
      systemic actions in vivo. Recent genetic technology sheds new light on this
      problem. This review focuses on the recent advances and newly arising issues
      regarding the mechanism of Ang II-induced cardiac fibrosis.

PMID- 10881749
TI  - Role of activation of the coagulation factor VIII in interaction with vWf,
      phospholipid, and functioning within the factor Xase complex.
AB  - Blood coagulation factor VIII (fVIII) in its nonactivated form circulates in
      plasma in a complex with von Willebrand factor (vWf). Upon activation by thrombin
      or factor Xa-mediated site-specific proteolysis, activated fVIII (fVIIIa) serves
      as a cofactor for factor IXa. This protein complex assembled on a phospholipid
      surface (factor Xase) activates factor X. This complex plays the key role in the
      intrinsic pathway of blood coagulation. We reviewed the molecular events
      triggered by fVIII activation, which are required for the assembly and
      functioning of the Xase complex, including fVIIIa dissociation from vWf and a
      significant increase of fVIII affinity for binding to the phospholipid surface.
      Both events are mediated by activation-related cleavage within fVIII light chain
      (LCh), releasing the 40 amino-acid N-terminal LCh peptide, which is followed by a
      conformational change within the C2 domain. The conformational change within LCh
      is also required for the optimal fVIII cofactor functioning within the factor
      Xase complex, exerted via fVIIIa interactions with phospholipid, factor IXa, and
      factor X. Since factor IXa not only stabilizes but also proteolytically
      inactivates fVIIIa within the factor Xase complex, the stability of the membrane
      bound fVIIIa in the presence and absence of factor IXa is discussed. In
      conclusion, we outline some new possible directions of the research. One of them
      arises from the recently demonstrated ability of plasma lipoproteins to provide a
      phospholipid surface for the assembly of the factor Xase complex in vitro. This
      finding raises a possibility that lipoproteins participate in factor Xase
      functioning in vivo and suggests a direct link between elevated levels of
      lipoproteins associated with atherosclerosis and increased thrombogenicity
      associated with this disease.

PMID- 10881750
TI  - Lipoprotein A-I structure.
AB  - High density lipoproteins are produced by the liver as protein-lipid complexes
      with a characteristic discoidal shape. A crystal structure is available for the
      chief protein component of these complexes, apolipoprotein A-I, but controversy
      about how this protein is situated with respect to the lipid components has
      flourished for lack of experimental techniques that can characterize protein
      structure in a lipid environment. New spectroscopic techniques developed to
      address this problem now indicate that apolipoprotein A-I is arranged as a
      helical belt around a bilayer of phospholipids. This is an important step towards
      understanding how these lipoproteins regulate cholesterol transport.

PMID- 10881751
TI  - Dominant role of the C-terminal domain in the binding of apolipoprotein(a) to the
      protein core of proteoglycans and other members of the vascular matrix.
AB  - The C-terminal domain of apolipoprotein(a) binds in vitro to the protein core of
      proteoglycans as well as fibrinogen and fibronectin, suggesting that this domain
      plays a role in anchoring lipoprotein(a) or free apolipoprotein(a) to the
      vascular subendothelial matrix.

PMID- 10881752
TI  - Inhibition of stress-activated p38 mitogen-activated protein kinase induces low
      density lipoprotein receptor expression.
AB  - We have recently shown that different signal transduction pathways initiated by a
      variety of agents converge on growth-responsive p42/44MAPK signaling cascade to
      induce low-density lipoprotein (LDL) receptor expression. Our recent
      demonstration that stress-activated p38MAPK negatively regulates LDL receptor
      expression in an isoform-specific manner via modulation of p42/44MAPK cascade
      represents a new dimension of complexity in the molecular communication that
      governs LDL receptor expression. The suggested one-way communication between
      p38MAPK and p42/44MAPK provides a potential mechanism for fine-tuning cellular
      levels of cholesterol in response to a diverse set of environmental cues,
      including stress. Cross talk between MAPKs opens new avenues toward understanding
      a variety of pathogenic processes; this makes them tempting targets for
      therapeutic interventions in cardiovascular diseases.

PMID- 10881753
TI  - Pathophysiological events during pregnancy influence the development of
      atherosclerosis in humans.
AB  - Pathophysiological events occurring during fetal development are increasingly
      recognized as influencing atherosclerosis throughout childhood and adolescence.
      Maternal hypercholesterolemia during pregnancy markedly increases fatty streak
      formation in human fetal arteries. Although fetal fatty streaks partially regress
      under normocholesterolemic conditions, progression of atherosclerosis in children
      of hypercholesterolemic mothers is much faster than in children of
      normocholesterolemic mothers. This cannot be accounted for by conventional risk
      factors of atherosclerosis or inherited genetic differences. The nature of the
      persistent changes in the fetal arterial wall responsible for increased
      atherogenesis in children and the mechanisms by which maternal
      hypercholesterolemia induces these changes need to be investigated, because they
      may offer important insights into the pathogenesis of atherosclerosis and because
      targeted interventions in mothers during pregnancy may yield considerable long
      term benefits.

PMID- 10881754
TI  - A novel role for cardiac neural crest in heart development.
AB  - It is well known that cardiac neural crest participates in development of the
      cardiac outflow septation and patterning of the great arteries. Less well known
      is that ablation of the cardiac neural crest leads to a primary myocardial
      dysfunction. Recent data suggests that the myocardial dysfunction occurs because
      of the absence of an interaction of neural crest and pharyngeal endoderm to alter
      signaling from the endoderm. Continuation of an FGF-like signal from the endoderm
      past a precise time in development appears to be detrimental to myocardial
      maturation.

PMID- 10881755
TI  - The impact of a disease-management program on the symptom experience of older
      women with heart disease.
AB  - This study describes the symptom experience of 570 older women with heart disease
      and evaluates a disease-management program's impact on symptoms over time. Women
      were randomly assigned to either usual care or a 4-week program ("Women take
      PRIDE") designed to improve self-regulation skills by focusing on increasing
      physical activity. At 4 months follow-up, program women, compared to controls,
      reported fewer total symptoms (p = 0.01) and decreased symptom frequency (p =
      0.02) and bothersomeness (p = 0.02). By 12 months, positive intervention effects
      emerged within the common cardiac and sleep and rest symptom categories. Program
      group women reported more improvements in symptoms likely to be affected by
      increasing physical activity at both follow-ups (p < 0.05).

PMID- 10881756
TI  - The influence of HIV-related knowledge and exposure fears on behavior change and
      incident STDs.
AB  - Using a sample of 678 HIV-seronegative women, we measured self-reports of HIV
      related cognitions, specifically knowledge, perceived exposure risks, and outcome
      expectations. We also ascertained prevalent and incident bacterial STDs and
      measured self-reports of behavioral risk reductions. We tested for associations
      between (a) cognitions and STD prevalence, (b) cognitions and incident STDs, (c)
      cognitions and behavioral risk reductions, and (d) risk reductions and incident
      STDs. Symptom knowledge was associated with lower prevalence, but not incidence.
      Beliefs in the efficacy of risk reductions showed a protective effect against
      incident STDs. Perceived exposure risk and symptom knowledge were associated with
      risk reduction behavior.

PMID- 10881757
TI  - A stimulus control intervention in the gynecological exam with sexual abuse
      survivors.
AB  - The effectiveness of a new examination gown, as a stimulus control intervention
      designed to reduce distress during the pelvic exam, was investigated in a sample
      of sexual abuse survivors and women without abuse histories. Sixty-nine
      participants from a women's health ambulatory center and a private practice in
      gynecology were randomly assigned to the experimental gown condition or the paper
      drape control group. One-third of the sample reported a history of childhood
      sexual abuse. Survivors reported higher anxiety during exams than did women
      without abuse histories. Women who wore the experimental gown reported more
      positive emotional and physical experiences of the exam. Further research is
      required to examine the trend showing that survivors who wore the experimental
      gown reported less anxiety during the examination than survivors who wore the
      control drape.

PMID- 10881758
TI  - Women's use of dual methods of sexual self-protection.
AB  - In a sample of college women at two private universities, this study examined
      dual use of self-protective measures, i.e., simultaneous use of condoms for
      disease prevention and birth control pills for contraception. Those who were dual
      users of condoms and birth control pills were in newer relationships, were less
      committed to their current relationships, and perceived their partners as more
      likely to have HIV or other STDs, as compared to college women using condoms
      only, birth control pills only, or no method. Dual use was unrelated to
      personality or health and risk behavior. Rather, dual use reflected a pattern of
      sexual self-protection based on risk management associated with concerns about
      consequences of sexual activity, that is STDs and conception, and not with more
      distal factors.

PMID- 10881759
TI  - Physical activity among African American and Latino middle school girls:
      consistent beliefs, expectations, and experiences across two sites.
AB  - Physical inactivity is a major public health concern. Low levels of physical
      activity are reported in many subgroups of women including adolescent girls. More
      data are needed to better understand factors related to physical activity
      participation in adolescent girls. Therefore, we explored adolescent girls'
      reasons for participating and not participating in physical activity. Two
      independent samples were taken in California and Texas; the total sample included
      thirty-four African American and Latino girls. Six focus groups were conducted by
      trained facilitators. Based on independent qualitative analyses, six replicated
      themes emerged from the focus groups. Fun, social support, and concern with body
      image facilitated participation in activity. In contrast, negative experiences in
      physical education classes, concerns about appearance after activity, and lack of
      opportunity impeded participation in activity. Overall, the girls showed an
      interest in physical activity and identified activity motivators and barriers. We
      discuss the implications of our findings for future research.

PMID- 10881760
TI  - Newspaper coverage of the breast implant controversy.
AB  - Newspaper coverage of the silicone breast implant controversy from 1992 through
      1996 was analyzed to determine whether women in the United States were provided
      with a fair and balanced account. The paper also addressed whether or not Dow
      Corning's public relations campaign impacted newspaper coverage. All stories from
      the New York Times, the Chicago Tribune and the Wall Street Journal were
      analyzed. Findings suggested that early coverage of the controversy focused on
      the health risks of silicone breast implants while later coverage focused on the
      financial situations of the implant manufacturers. The most-interviewed sources
      were spokespersons for the implant manufacturers, while the least-interviewed
      sources were women with implants. The findings suggested that reporting patterns
      were influenced by the public relations efforts of the implant manufacturer,
      raising questions concerning the coverage of health care controversies involving
      large corporations seeking refuge from litigation.

PMID- 10881761
TI  - Gender differences in sarcoidosis: symptoms, quality of life, and medical
      consumption.
AB  - The aim of this study was to examine gender differences in quality of life (QOL)
      and in constitutional symptoms that coincide with sarcoidosis. The study
      population included 1026 sarcoidosis patients--all members of the Dutch
      Sarcoidosis Society--who completed the WHOQOL-100 and a symptom checklist. Women
      experienced more symptoms than men. With regard to QOL, male and female patients
      who suffered from symptoms differed in the broader domains of Physical Health and
      Psychological Health. Specific facets reflected pain, sleep, positive affect,
      appearance, mobility, and activities of daily living. Future studies should focus
      on the different experience of the disease between male and female patients more
      extensively. Studies are needed to evaluate whether the differences in the
      present study between male and female sarcoidosis patients are caused by a
      subject selection bias or life style differences; have a genetic, hormonal or
      biological base; or just are an epiphenomenon.

PMID- 10881762
TI  - Targeted tuberculin testing and treatment of latent tuberculosis infection.
      American Thoracic Society.
AB  - This statement provides new recommendations for targeted tuberculin testing and
      treatment regimens for persons with latent tuberculosis infection (LTBI) and
      updates previously published guidelines (1,2). This statement is issued in
      recognition of the importance of these activities as an essential component of
      the TB Elimination Strategy promoted by the U.S. Public Health Service Advisory
      Council on the Elimination of Tuberculosis, and reports the deliberations of
      expert consultants convened by the American Thoracic Society (ATS) and Centers
      for Disease Control and Prevention (CDC). Isoniazid for 6-12 mo has been the
      mainstay of treatment for LTBI in the United States for more than 30 yr. However,
      the application of isoniazid for LTBI has been limited because of poor adherence,
      due to the relatively long duration of treatment required, and because of
      concerns about toxicity. Therefore, there has been interest in the development of
      shorter, rifampin-based regimens as alternatives to isoniazid for the treatment
      of LTBI. During the past decade, a series of studies of "short-course" treatment
      of LTBI in persons with human immunodeficiency virus (HIV) infection has been
      undertaken. The results of these trials have recently become available, and the
      in-depth analyses of these and prior studies of isoniazid form the scientific
      basis of the treatment guidelines presented in this report. In addition, many
      changes to previous recommendations regarding testing for and treatment of LTBI
      are presented (Table 1).

PMID- 10881763
TI  - Use of medical care, police assistance, and restraining orders by women reporting
      intimate partner violence--Massachusetts, 1996-1997.
AB  - Approximately 1.5 million women in the United States are physically or sexually
      assaulted by an intimate partner (IP) each year (1). The Woman Abuse Tracking in
      Clinics and Hospitals (WATCH) Project at the Massachusetts Department of Public
      Health analyzed data from the 1996 and 1997 Behavioral Risk Factor Surveillance
      System (BRFSS) in Massachusetts to 1) estimate the percentage of women aged 18-59
      years experiencing intimate partner violence (IPV) who used medical care, police
      assistance, and restraining orders during the preceding 5 years, 2) determine
      where women experiencing IPV went for medical care, and 3) examine the overlap in
      use of these three services. This report describes the results of these analyses,
      which indicate that a higher percentage of women aged 18-59 years use police
      assistance rather than obtain a restraining order or seek medical care.

PMID- 10881764
TI  - Unexplained illness and death among injecting-drug users--Glasgow, Scotland;
      Dublin, Ireland; and England, April-June 2000.
AB  - Since April 19, 2000, 30 injecting-drug users (IDUs) died or were hospitalized
      with unexplained severe illness in Glasgow, Scotland. Illness was characterized
      by extensive local inflammation at a subcutaneous or intramuscular injection site
      often followed by hypotension and circulatory collapse. Since April 24, 2000, 15
      IDUs in Dublin, Ireland, and 14 IDUs in England with similar illnesses have been
      identified. Despite debridement and broad spectrum antibiotics, 30 (51%) of the
      59 patients in all three countries have died. This report further describes the
      clinical syndrome and key epidemiologic features of the illness as characterized
      by a preliminary investigation by health authorities in Scotland, Ireland,
      England, and the United States (1).

PMID- 10881765
TI  - Illnesses associated with use of automatic insecticide dispenser units--selected
      states and United States, 1986-1999.
AB  - To control indoor flying insects, restaurants and other businesses commonly use
      pyrethrin and pyrethroid insecticides sprayed from automatic dispensing units.
      Usually placed near entrances, these units are designed to kill flying insects in
      food service or work areas. On May 18, 1999, the Florida Department of Health
      (FDH) was notified by the Florida Department of Business and Professional
      Regulation (DBPR) that during May 12-17, three persons developed pesticide
      related illnesses associated with improperly placed automatic insecticide
      dispensers. After FDH conducted a follow-up investigation and notified CDC's
      National Institute for Occupational Safety and Health (NIOSH) of this event,
      surveillance data were reviewed to identify additional cases of pesticide-related
      illnesses associated with automatic insecticide dispensers. Data were provided by
      the Toxic Exposure Surveillance System (TESS), the California Department of
      Pesticide Regulation (CDPR), the Montana Department of Agriculture (MDA), the
      National Pesticide Telecommunications Network (NPTN), and the Washington State
      Department of Health (WSDH)*. This report describes cases, summarizes
      surveillance data for pesticide-related illnesses associated with automatic
      insecticide dispensers, and provides recommendations for safe dispenser use.

PMID- 10881766
TI  - Probable locally acquired mosquito-transmitted Plasmodium vivax infection-
      Suffolk County, New York, 1999.
AB  - In the United States, malaria transmission was eliminated in the 1940s, and
      malaria eradication was certified in 1970 (1). Since then, 60 small localized
      outbreaks of probable mosquito-transmitted malaria have been reported to CDC (2
      6). Before 1995, the number of imported malaria cases reported to the Suffolk
      County (New York) Department of Health Services ranged from zero to eight per
      year. Since 1995, seven to 17 cases per year have been reported. In all of these
      cases, a history of residing in or traveling to an area with endemic malaria
      outside the United States was confirmed. This report describes the investigation
      of two cases of Plasmodium vivax malaria that occurred in Suffolk County in
      August 1999; the patients had no history of travel outside of the United States.

PMID- 10881767
TI  - When antihypertensive monotherapy fails: fixed-dose combination therapy.
AB  - BACKGROUND: Antihypertensive monotherapy fails to control blood pressure in many
      patients. METHODS: Data on the efficacy and tolerance of fixed dose angiotensin
      converting enzyme (ACE) inhibitor/calcium antagonist combinations were reviewed,
      since they are the most widely prescribed medications for hypertension. RESULTS:
      A fixed-dose combination of two drug classes is an option for hypertension
      treatment. Four fixed-dose ACE inhibitor/calcium antagonist combinations are
      available. They achieve superior blood pressure control with no increase in
      adverse events compared with their monotherapy components. In addition, they
      antagonize some class-specific adverse effects and may exhibit beneficial effects
      on target organ disease, such as renal dysfunction and left ventricular
      hypertrophy. CONCLUSIONS: Fixed-dose combination therapy is an attractive option
      when reasonable doses of initial antihypertensive monotherapy fail. Use of such
      combinations could increase patient compliance, by virtue of better tolerance
      compared with increased-dose monotherapy and simplicity of administration.

PMID- 10881768
TI  - Drug-facilitated sexual assault ('date rape').
AB  - In the past few years, drug-facilitated sexual assaults have received widespread
      media coverage. In addition to alcohol, the most frequently used date-rape drug,
      flunitrazepam (Rohypnol), a fast-acting benzodiazepine, and gamma-hydroxybutyrate
      (GHB) and its congeners are among the most popular drugs used for this purpose.
      The latter drug is easily procured at some gymnasiums, popular bars, discos, and
      rave clubs, as well as over the Internet. Perpetrators choose these drugs because
      they act rapidly, produce disinhibition and relaxation of voluntary muscles, and
      cause the victim to have lasting anterograde amnesia for events that occur under
      the influence of the drug. Alcoholic beverages potentiate the drug effects. We
      review several date-rape drugs, provide information on laboratory testing for
      them, and offer guidelines for preventing drug-facilitated sexual assault.

PMID- 10881769
TI  - Recurrent coagulopathy after antivenom treatment of crotalid snakebite.
AB  - BACKGROUND: We studied whether recurrence of coagulopathy, defined as the return
      of a coagulation abnormality after initial normalization, occurred after the use
      of antivenin (Crotalidae) polyvalent. METHODS: A retrospective, blinded,
      descriptive analysis of 354 consecutive cases of North American crotalid snake
      envenomation was done. Inclusion criteria were documented clinical evidence of
      crotalid snakebite, presence of a coagulopathy (platelet count <150,000/mm3,
      prothrombin time above normal, or fibrinogen level <150 mg/dL), and treatment
      with antivenin (Crotalidae) polyvalent. RESULTS: Of 112 cases with a coagulopathy
      extending beyond 6 hours after envenomation, 31 had sufficient coagulopathy
      testing to detect recurrence. Fourteen of these patients (45%) had recurrence of
      coagulopathy, and two cases were severe (fibrinogen level 29 mg/dL; platelet
      count 36,000/mm3). CONCLUSION: Recurrence of coagulopathy after envenomation by
      North American crotalid snakes may occur after use of antivenin (Crotalidae)
      polyvalent and can result in severe coagulation abnormalities.

PMID- 10881770
TI  - Penetrating neck injuries.
AB  - Penetrating neck trauma may be managed operatively or nonoperatively, depending
      on precise anatomic location. Conservative management of zone II injuries is
      currently an issue under debate. We present a brief case report followed by a
      description of the current strategies for operative exploration and diagnostic
      maneuvers in penetrating neck injuries. Support for both expectant and operative
      management of zone II injuries is given. We conclude that for zone II injuries,
      mandatory exploration by an experienced surgeon is a safe approach and that
      conservative management must be undertaken with extreme caution.

PMID- 10881771
TI  - Inpatients with menometrorrhagia: etiologies, treatments, and outcomes.
AB  - BACKGROUND: Abnormal uterine bleeding is commonly seen in emergency departments
      and gynecologic clinics. In a southern, inner-city hospital, a seemingly large
      number of women are admitted with life-threatening anemia of benign gynecologic
      origin. We examine its causes, review treatments and outcomes, and discuss
      optimization of therapy. METHODS: A chart review of patients requiring emergency
      admission for anemia of gynecologic origin yielded 48 patients from July 1, 1994,
      through April 30, 1998. Patients with known or obvious gynecologic malignancies
      were excluded. RESULTS: Of 48 patients, 69% were black. Mean age was 41 years.
      Sixty-three percent had had no previous treatment. Almost one fourth had a
      history of mental illness and/or substance abuse. Two thirds had uterine
      leiomyomata. Most (81%) required transfusion; 25% had surgery during initial
      hospitalization. Of those who did not receive definitive therapy (hysterectomy),
      13% were subsequently readmitted for active bleeding and/or symptomatic anemia.
      CONCLUSIONS: Our study patients were admitted with potentially life-threatening
      anemia. All were adequately resuscitated using a variety of measures, including
      high-dose estrogen therapy and transfusion. Optimal therapy for those requiring
      emergency treatment should include hormonal therapy and transfusion if necessary,
      early surgical intervention unless otherwise contraindicated, and close follow-up
      until definitive therapy is achieved.

PMID- 10881772
TI  - Medical exclusion of sick children from child care centers: a plea for
      reconciliation.
AB  - BACKGROUND: Policies for excluding ill children from child care can affect
      parental absenteeism from the workplace and the utilization of pediatric health
      care resources. METHODS: We surveyed a representative sample of 310 child care
      centers throughout Virginia to assess policies for excluding children with fever,
      common upper respiratory tract illnesses, or head lice. RESULTS: Of the 183
      center directors (59%) who returned completed surveys, 119 (69%) considered a
      temperature of 100.0 degrees F to 100.4 degrees F to represent fever, but methods
      for measuring temperature varied widely. Most centers excluded children with low
      grade fever, even in the absence of changes in their behavior. Other low
      threshold policies could exclude afebrile children with white nasal or eye
      discharge and children with hair nits, even after treated with a pediculicidal
      shampoo. CONCLUSIONS: Exclusion policies among child care centers in Virginia
      vary widely and often are inconsistent with current standards of medical
      practice. More uniform implementation of exclusion policies established by
      national consensus panels of experts is needed to reduce unnecessary exclusion of
      children from child care centers.

PMID- 10881773
TI  - Daily smoking by Louisiana students: sixth through twelfth grades, 1996-1997.
AB  - OBJECTIVES: We sought to determine the prevalence of daily smoking in Louisiana
      in grades 6 through 12 and to compare Louisiana students' daily smoking to that
      of national student and Louisiana adult rates. METHODS: A statewide, randomized,
      stratified classroom-based survey of 11,736 subjects was done for the school year
      1996-1997. RESULTS: We found that 17.3% of sixth grade students smoked daily,
      increasing to 36.1% in twelfth grade. Native American (43.7%), white (37.8%), and
      public school (28.5%) students had the highest rates of daily smoking. Males and
      females smoked at similar rates. Louisiana students in grades 8, 10, and 12
      smoked daily at much higher rates (331%, 193%, and 146%, respectively) than
      comparable national samples. In 1997, Louisiana students smoked daily at higher
      rates than did Louisiana adults (28.9% vs 24.6%), primarily due to higher rates
      of smoking in student females (27.1%) compared to adult females (20.4%).
      CONCLUSIONS: Student smoking in Louisiana is a significant public health problem.

PMID- 10881774
TI  - Adherence to prescription medications among medical professionals.
AB  - BACKGROUND: We evaluated adherence to medication usage by health care
      professionals to estimate the expected upper limit of adherence among the general
      population. METHODS: In a self-administered survey, physicians and nurses were
      asked about their use of prescribed medications for acute and chronic illnesses.
      The settings were a teaching hospital, employee health service, medical college,
      and educational conferences. RESULTS: Among 435 respondents, 301 physicians and
      nurses had medications prescribed for acute and/or chronic illnesses within 2
      years of the survey. Of 610 prescribed medications, > or =80% were taken as
      prescribed, with a 77% compliance rate for short-term medications and 84% for
      long-term medications. Older age was associated with better adherence, whereas a
      greater number of doses per day was associated with poorer adherence.
      CONCLUSIONS: Approximately 80% of respondents reported properly taking
      prescription medications > or =80% of the time. Given the nature of the study
      population, it is unlikely that a nonclinical trial population will consistently
      achieve better adherence without specific interventions.

PMID- 10881775
TI  - Blood pressure in acute vaso-occlusive crises of sickle cell disease.
AB  - OBJECTIVE: We compared blood pressure (BP) in patients with sickle cell disease
      (SCD)-related crises and black patients without SCD. METHODS: We retrospectively
      reviewed charts of emergency department (ED) patients with SCD crises in a 2-year
      period, recording BPs and demographic and SCD data. A cohort of consecutive black
      patients without SCD was compared. RESULTS: Included were 459 SCD-related visits,
      187 by men and 272 by women, representing 106 patients. Women had significantly
      lower BP than men, diastolic BP was significantly lower in patients with
      hemoglobin SS disease than in those with hemoglobin SC disease, and systolic BP
      was significantly lower in patients with bilateral versus unilateral pain. One
      SCD patient had a history of hypertension. The 125 non-SCD patients, excluding 25
      with a history of hypertension, had significantly higher systolic and diastolic
      BP than patients in SCD crisis. CONCLUSION: No patients seen in SCD crisis were
      hypertensive. Patients who were female, had SS disease, or had bilateral pain had
      lower BP. Significantly higher BP and more hypertension occurred in black
      patients without SCD.

PMID- 10881776
TI  - Complications of lower extremity arteriovenous grafts in patients with end-stage
      renal disease.
AB  - BACKGROUND: More data are needed to assess lower extremity angioaccess sites for
      hemodialysis. METHODS: We did a retrospective review of 843 consecutive hospital
      records of upper and lower extremity arteriovenous (AV) fistulas from 1992 to
      1996. RESULTS: Lower extremity grafts accounted for 16% (134/843) of patients in
      this series. Complications occurred in 58 of 134 patients (43%) and were more
      prevalent in women, blacks, diabetic, and hypertensive patients, but not of
      statistical significance. Dialysis was done for a mean duration of 13.3 years,
      with a mean graft patency rate of 13.8 months. The 12-month survival rate of
      lower extremity AV grafts was 62% (83/134). Complications in the lower extremity
      AV graft group (58 patients) included infections in 27 patients (46%), thrombosis
      within 30 days in 16 (28%), pseudoaneurysm in 9 (16%), and graft hemorrhage in 6
      (10%). CONCLUSIONS: There is a decreased patency rate in lower extremity AV
      grafts.

PMID- 10881777
TI  - Camphor hepatotoxicity.
AB  - We report a case of hepatotoxicity in a 2-month-old baby after a camphor
      containing cold remedy was applied dermally. Liver function tests returned to
      normal after the application of the cold remedy was discontinued. Ingestion of
      camphor can cause severe liver and central nervous system injury, and
      neurotoxicity has been observed after exposure to camphor through the skin.
      Hepatotoxicity after dermal application of camphor has never been reported. This
      report emphasizes the common use of cold remedies that are usually not beneficial
      and may be potentially dangerous.

PMID- 10881778
TI  - Complex enterocutaneous fistula: closure with rectus abdominis muscle flap.
AB  - Most enterocutaneous fistulas are caused by complications of abdominal surgery
      that may result from anastomotic failure, poor blood supply, or iatrogenic bowel
      injuries. Mortality rates are high when associated sepsis and malnutrition are
      uncontrolled. Fistulas that occur late and those that recur spontaneously present
      more difficulty and may close spontaneously in less than 30% of cases. Mortality
      rates in patients with complex enterocutaneous fistulas may reach 60% to 80%.
      When traditional conservative surgeries of fistulous tract excision, bowel
      mobilization, and resection with primary end-to-end anastomosis fail, a more
      aggressive approach is required. The rectus abdominis muscle flap has been
      extensively studied and used in a wide variety of abdominal, vaginal, and
      perineal repairs. We report successful closure of complex enterocutaneous
      fistulas with a rectus abdominis muscle flap in a complicated case.

PMID- 10881779
TI  - Recurrent cholangiocarcinoma: negative autopsy results after aggressive
      management.
AB  - Cholangiocarcinoma is one of the most common malignancies of the biliary tree.
      Most cases are perihilar. Cholangiocarcinoma usually has an indolent, slowly
      progressive course and is associated with a high mortality rate. In this article,
      we discuss the management of perihilar cholangiocarcinoma by radiation therapy
      and chemotherapy in a case in which no recurrence was found on autopsy.

PMID- 10881780
TI  - Superior mesenteric artery syndrome: an uncommon cause of intestinal obstruction.
AB  - Superior mesenteric artery (SMA) syndrome is an atypical cause of high intestinal
      obstruction, most frequently occurring in patients who have had rapid weight
      loss. Identification of this syndrome can be a diagnostic dilemma and is
      frequently made by exclusion. The most characteristic symptoms are postprandial
      epigastric pain, eructation, fullness, and voluminous vomiting. The symptoms are
      caused by compression of the third portion of the duodenum against the posterior
      structures by a narrow-angled SMA. When nonsurgical management is not possible or
      the problem is refractory, surgical intervention is necessary. We report a case
      of SMA syndrome in a patient without a history of rapid weight loss. The patient
      complained of early satiety, nausea, and vomiting of partially digested food
      worsening over 2 years. Diagnostic evaluation revealed compression of the third
      portion of the duodenum by the SMA with resultant proximal dilatation. The
      patient successfully had duodenojejunal anastomosis.

PMID- 10881781
TI  - Spontaneous rupture of spleen due to Q fever.
AB  - Spontaneous rupture of the spleen is a rare complication of acute Q fever
      infection. Only two cases have been reported, both in Europe. This is the first
      reported case of spontaneous rupture of the spleen caused by acute Q fever in the
      United States.

PMID- 10881782
TI  - Pleural fluid and serum eosinophilia: association with fluoxetine hydrochloride.
AB  - We report the case of a patient who was treated with fluoxetine hydrochloride
      (Prozac) for depression. Approximately 8 weeks into the treatment, an
      eosinophilic pleural effusion and serum eosinophilia developed. An extensive
      workup for the etiology of eosinophilic pleural effusion was unrevealing. Pleural
      biopsy showed a nonspecific inflammatory reaction and mild fibrosis. The pleural
      effusion and eosinophilia resolved within a few weeks of cessation of the drug.
      Fluoxetine can be associated with pleural and serum eosinophilia, possibly
      through an allergic-mediated reaction.

PMID- 10881783
TI  - Toxoplasma gondii pneumonia in a pancreas transplant patient.
AB  - A 41-year-old woman had fever of 3 days' duration. She had had pancreas
      transplantation 2 years previously and had recently completed a course of
      antirejection medication. Temperature spikes occurred during treatment with broad
      spectrum antibiotics. No obvious cause for the fever was found. The patient's
      condition worsened, with development of shortness of breath, bilateral pulmonary
      infiltrates on chest radiographs, sepsis, and shock. Fiberoptic bronchoscopy with
      bronchoalveolar lavage showed the presence of Toxoplasma gondii. Pyrimethamine
      and clindamycin were started, and the patient improved. Toxoplasma gondii occurs
      in contaminated food containing oocysts or cysts. Organ transplantation and blood
      transfusions are other routes of transmission. Most recent cases have occurred in
      human immunodeficiency virus (HIV) patients with reactivation of previous
      infection. Serology and tissue biopsies are used for diagnosis. Treatment
      includes a combination of pyrimethamine and sulfadiazine or trisulfapyrimidines.

PMID- 10881784
TI  - Intracanalicular meningioma.
AB  - Intracanalicular meningiomas are extremely rare and difficult to differentiate
      from intracanalicular vestibular schwannomas. We report an unusual case of a
      posterior fossa meningioma in the proximal internal auditory canal that was
      originally diagnosed as a vestibular schwannoma due to its appearance on magnetic
      resonance imaging. However, closer inspection of the preoperative neuroimages
      revealed features inconsistent with vestibular schwannoma that suggested the
      possibility of other less common lesions.

PMID- 10881785
TI  - FGFR3 gene mutation (Gly380Arg) with achondroplasia and i(21q) Down syndrome:
      phenotype-genotype correlation.
AB  - We report the case of a boy with achondroplasia and i(21q) Down syndrome. Besides
      craniofacial features typical in Down syndrome, the skeletal findings of
      achondroplasia dominate the clinical picture. The diagnosis of Down syndrome was
      based on clinical features and the cytogenetic finding of i(21q) trisomy 21. The
      diagnosis of achondroplasia was based on the presence of clinical and
      radiographic findings and confirmed by the presence of a common FGFR3 gene
      mutation (Gly380Arg) detected by restriction enzyme analysis and sequencing of
      the polymerase chain reaction products. This is the first report of
      achondroplasia associated with i(21q) Down syndrome.

PMID- 10881786
TI  - Peliosis hepatis after treatment with 2-chloro-3'-deoxyadenosine.
AB  - Peliosis hepatis is an unusual disorder associated with a variety of diseases and
      treatments. This is the first report of peliosis hepatis associated with
      administration of 2-chloro-3'-deoxyadenosine. The literature is reviewed.

PMID- 10881787
TI  - Coronary arteriovenous fistula with papillary muscle rupture.
AB  - We describe a patient who had a coronary arteriovenous fistula (CAVF) and whose
      mitral valve papillary muscle ruptured from chronic ischemia due to a coronary
      steal phenomenon. He was treated surgically with ligation of the CAVF (left
      circumflex to coronary sinus), coronary artery bypass grafting, and mitral valve
      replacement. This is the first report of papillary muscle rupture related to
      CAVF.

PMID- 10881788
TI  - Prochlorperazine-induced extrapyramidal effects mimicking meningitis in a child.
AB  - Certain medications, such as the phenothiazines, may cause side effects that
      result in neck stiffness and may actually mimic the presentation of meningitis,
      especially in children. Despite the controversial use of antiemetics, they
      continue to be used in children with viral gastroenteritis. I describe the case
      of a child who had a febrile seizure and meningismus during the course of a viral
      gastroenteritis, not due to meningitis but to the untoward side effect of an
      antiemetic. Clinicians must be aware that these medications may cause
      extrapyramidal side effects that may mimic other more serious diseases and lead
      to unnecessary evaluations; therefore, their use cannot be strongly encouraged.
      If antiemetics are prescribed, physicians should emphasize possible side effects
      so that corrective treatment can be initiated promptly.

PMID- 10881789
TI  - Noncaseating granulomatous disease in common variable immunodeficiency.
AB  - Patients with common variable immunodeficiency (CVID) are occasionally recognized
      to have a concurrent noncaseating granulomatous disease. The granulomatous
      disease (GD) associated with CVID shares many clinical properties typical of
      sarcoidosis. Some investigators speculate that the GD-CVID is actually
      sarcoidosis that is expressed atypically because of the patient's
      immunodeficiency. Clinical differences, however, have led other investigators to
      speculate that the GD-CVID is a distinct "sarcoid-like" granulomatous process.

PMID- 10881790
TI  - Literature, medicine, and the liberally educated physician.

PMID- 10881791
TI  - Treating unrelated disorders in patients with chronic diseases.

PMID- 10881792
TI  - The last of the real men.

PMID- 10881793
TI  - Cardiothoracic surgery in the new millennium: challenges and opportunities in a
      time of paradox.

PMID- 10881794
TI  - The Medicare program and thoracic surgery: challenges for the new century.

PMID- 10881795
TI  - Postoperative drug therapy to extend survival after coronary artery bypass
      grafting.

PMID- 10881796
TI  - Res ipsa loquitur: protecting the brain in the new millennium, "Outcomes 2000".

PMID- 10881797
TI  - Education or training in cardiothoracic surgery?

PMID- 10881798
TI  - Content of thoracic residency training and its relevance to the practice of
      medicine.
AB  - BACKGROUND: The Thoracic Surgery Directors Association (TSDA) curriculum book
      provides learning objectives for a thoracic surgery residency. Our purpose was to
      evaluate the relevance of these objectives through feedback from recent
      graduates. METHODS: Graduates of multiple TSDA programs were mailed a 50-item
      questionnaire. Survey items were objectives from the TSDA curriculum book
      representing six areas of thoracic surgery. Graduates rated each objective for
      adequacy of instruction and relevance to their current practice on Likert-type
      scales. RESULTS: Two hundred twenty-eight surveys were included in the analysis.
      Despite excellent operating room education, graduates across subspecialty lines
      reported the need for improved education in "nonoperative" subjects. Graduates
      practicing cardiac surgery reported little relevance of their general thoracic
      educational experience. Conversely, graduates practicing general thoracic surgery
      expressed the need for more/better educational experiences in thoracic oncology
      and esophageal surgery. CONCLUSIONS: Contemporary thoracic surgical education can
      be improved. A strong need for improvement exists in the teaching of
      "nonoperative" subjects. As graduates elect careers in thoracic subspecialties, a
      need exists to align thoracic surgery educational experiences with ultimate
      career goals of residents.

PMID- 10881799
TI  - Aortic valve replacement: comparison of late survival between autografts and
      homografts.
AB  - BACKGROUND: Autografts (AG) and homografts (HG) are currently considered the best
      choices for replacement of the diseased aortic valve in young adults, although
      few data exist comparing their late outcome. Nonhomogeneous populations and
      evolving operative techniques confound existing comparisons. METHODS: To help
      clarify these issues, we reviewed our results with 238 hospital survivors (aged
      17 to 82 years) undergoing operation between 1986 and 1999. All operations were
      done as root replacements, and patients needing concomitant valve replacement
      were excluded. RESULTS: Mean age of the 145 AGs and 93 HGs was 35 +/- 13 years
      and 49 +/- 17 years, respectively (p < 0.001). Previous aortic valve replacement
      was done in 12 (8%) AG and 32 (34%) HG patients (p = 0.001), and active
      endocarditis was present at time of current operation in 10 (7%) AG and 25 (27%)
      HG patients (p = 0.001). Maximum follow-up was 12.2 years for AGs and 12.8 years
      for HGs. Late survival at 10 years was 77% +/- 11% for AGs and 67% +/- 9% for HGs
      (p = 0.13). Freedom from AG or HG degeneration at 10 years was 97% +/- 2% and 79%
      +/- 10% (p = 0.63). Freedom from valve-related complications at 10 years was 73%
      +/- 10% and 64% +/- 10% (p = 0.93), respectively. Freedom from all reoperations
      at 10 years was 88% +/- 5% for AG and 72% +/- 11% for HG (p = 0.67). CONCLUSIONS:
      Autografts and HGs have comparable late survival. The incidence of valve
      degeneration is low for both AG and HG up to about 8 years at which point there
      may be a trend toward an advantage for AG over the HG, suggesting benefit for the
      younger patient.

PMID- 10881800
TI  - Options for repair of a bicuspid aortic valve and ascending aortic aneurysm.
AB  - BACKGROUND: Intrinsic abnormality of the aortic wall may explain the association
      of bicuspid aortic valves with ascending aortic aneurysms. Separate valve and
      graft repair of such lesions, rather than composite valve graft replacement, is
      more straightforward but leaves potentially abnormal sinuses behind. METHODS:
      Between January 1985 and January 1998, 45 patients underwent separate valve and
      graft (n = 27) or composite valve graft (n = 18) for an ascending aortic aneurysm
      and bicuspid aortic valve. Perioperative events and late results were compared.
      RESULTS: Patients undergoing separate valve and graft were older (mean age, 60 +/
      13 vs 42 +/- 12 years, p < 0.001) and were more likely to have purely stenotic
      (48% vs 6%, p = 0.003) than purely regurgitant (11% vs 72%, p < 0.001) disease.
      They were also more likely to require concomitant coronary artery bypass grafting
      (56% vs 6%, p = 0.001). There were no significant differences in operative risk
      and no known late complications related to recurrent aneurysms. CONCLUSIONS: Root
      replacement with a composite valve graft can be accomplished with low operative
      risk and is the first choice for repair of this lesion. Separate valve and graft
      repair, however, yields satisfactory early and late results and remains an
      acceptable option, especially when the coronary ostea are not displaced or when
      concomitant procedures must be performed.

PMID- 10881801
TI  - Anterior thoracotomy wound complications in minimally invasive direct coronary
      artery bypass.
AB  - BACKGROUND: The minimally invasive anterior thoracotomy for beating heart
      coronary bypass offers a modest 10-cm incision and avoids the morbidity of
      extracorporeal circulation. This study examines minimally invasive direct
      coronary artery bypass (MIDCAB) wound complications and contributing comorbid
      factors. METHODS: A retrospective, single-institution review of 165 consecutive
      MIDCAB cases performed between March 1996 and August 1999 examined all wound
      abnormalities. Two surgeons performed all cases. RESULTS: Wound complications
      occurred in 15 patients (9.1%), including three (1.8%) incisional hernias, four
      (2.4%) superficial dehiscences, three (1.8%) wound infections, three (1.8%)
      chronic pain syndromes, and two (1.2%) seromas. Two patients with incisional
      hernias required operative repair. The remaining wound abnormalities responded to
      conservative therapy. Two chronic pain syndrome cases resolved spontaneously, but
      the third required advanced pain management. In contrast to MIDCAB, the
      sternotomy wound complications proved significantly less prevalent (n = 5259,
      1.1% vs 9.1%, p < 0.005). CONCLUSIONS: Although MIDCAB offers several advantages
      over standard approaches, these data suggest that anterior thoracotomy wound
      complications are not insignificant and may be underestimated by those exploring
      minimally invasive options.

PMID- 10881802
TI  - Experience with postinfarction left ventricular free wall rupture.
AB  - BACKGROUND: Postinfarction rupture of the left ventricle is a rare event in which
      approach is not clearly standardised and outcome after repair is unknown. Our
      experience with this pathology was reviewed to analyze methods of repair and
      assess outcome beyond the patient's hospitalisation. METHODS: Five patients
      underwent surgical repair of a postinfarction ventricular rupture between 1990
      and 1998. Electromechanical dissociation (3 patients) and sudden hypotension and
      bradycardia (2 patients) were clinical indicators of rupture. Four patients
      underwent repair with cardiopulmonary bypass and 1 patient without. Repair
      consisted of epicardial patching (2 patients), direct suture (1 patient), infarct
      exclusion (1 patient), and debridement and patch closure (1 patient) of the
      rupture. Myocardial revascularization was performed in 3 patients and mitral
      valve repair in 1 patient. RESULTS: A satisfactory hemodynamic state was restored
      and bleeding was controlled in all patients. Two patients died postoperatively
      and another patient died 4 months after hospital discharge as a result of cardiac
      failure and/or sepsis. The other 2 patients are alive and in excellent condition
      6 and 30 months respectively after repair. CONCLUSIONS: Postinfarction rupture of
      the left ventricle bears a high mortality, but survival with an excellent quality
      of life is possible after surgical repair.

PMID- 10881803
TI  - Differential perfusion: a new technique for isolated brain cooling during
      cardiopulmonary bypass.
AB  - BACKGROUND: The purpose of this study was to determine the feasibility of
      differential perfusion of the aortic arch and descending aorta during
      cardiopulmonary bypass using a cannula designed for aortic segmentation. METHODS:
      Pigs weighing 57 kg (n = 8), underwent cardiopulmonary bypass using the dual
      lumen aortic cannula. An inflatable balloon separated proximal (aortic arch) and
      distal (descending aorta) ports. During differential perfusion, the aorta was
      segmented and the arch and descending aorta perfused differentially using
      parallel heat exchangers. Ability to independently control brain and body
      temperature, cardiopulmonary bypass flow rate and mean arterial blood pressure
      was determined. RESULTS: During differential perfusion cerebral hypothermia (27
      degrees C) with systemic normothermia (38 degrees C) was established in 23
      minutes. Independent control of arch and descending aortic flow and mean arterial
      blood pressure was possible. Analysis of internal jugular venous O2 saturation
      data indicated an increase in the ratio of cerebral O2 supply to demand during
      differential perfusion. CONCLUSIONS: A cannulation system segmenting the aorta
      allows independent control of cerebral and systemic perfusion. This device could
      provide significant cerebral protection while maintaining the advantages of warm
      systemic cardiopulmonary bypass temperatures.

PMID- 10881804
TI  - An experimental model of chronic myocardial hibernation.
AB  - BACKGROUND: Hibernating myocardium describes persistently impaired ventricular
      function at rest caused by reduced coronary blood flow. However, a realistic
      animal model reproducing this chronic ischemic state does not exist. The purpose
      of this study was to explore whether chronic low-flow hibernation could be
      produced in swine. METHODS: Miniswine underwent 90% stenosis of the left
      circumflex coronary artery. Positron emission tomography and dobutamine stress
      echocardiography were performed 3 and 30 days (n = 6) or 14 days (n = 4) after
      occlusion to evaluate myocardial blood flow and viability. Triphenyl tetrazolium
      chloride assessed percent infarction. Electron microscopy was used to identify
      cellular changes characteristic of hibernating myocardium. RESULTS: Positron
      emission tomography (13N-labeled-ammonia) 3 days after occlusion demonstrated a
      significant reduction in myocardial blood flow in the left circumflex
      distribution. This reduced flow was accompanied by increased glucose use (18F
      fluorodeoxyglucose), which is consistent with hibernating myocardium. Thirty days
      after occlusion, positron emission tomography demonstrated persistent low flow
      with increased glucose use in the left circumflex distribution. Dobutamine stress
      echocardiography 3 days after occlusion demonstrated severe hypocontractility at
      rest in the left circumflex region. Regional wall motion improved with low-dose
      dobutamine followed by deterioration at higher doses (biphasic response),
      findings consistent with hibernating myocardium. The results of dobutamine stress
      echocardiography were unchanged 30 days after occlusion. Triphenyl tetrazolium
      chloride staining (n = 6) revealed a mean of 8% +/- 2% infarction of the area-at
      risk localized to the endocardial surface. Electron microscopy (n = 4) 14 days
      after occlusion demonstrated loss of contractile elements and large areas of
      glycogen accumulation within viable cardiomyocytes, also characteristic of
      hibernating myocardium. CONCLUSIONS: Chronic low-flow myocardial hibernation can
      be reproduced in an animal model after partial coronary occlusion. This model may
      prove useful in the study of the mechanisms underlying hibernating myocardium and
      the use of therapies designed to improve blood flow to the heart.

PMID- 10881805
TI  - Intraoperative amiodarone as prophylaxis against atrial fibrillation after
      coronary operations.
AB  - BACKGROUND: New onset of atrial fibrillation is a frequent complication after
      coronary artery bypass grafting and is a major cause of postoperative morbidity.
      Preoperative oral treatment with amiodarone hydrochloride has been shown to be
      efficacious as prophylaxis. The present study investigated whether intraoperative
      use of intravenous amiodarone has a preventive effect on the incidence of atrial
      fibrillation after coronary revascularization. METHODS: In a prospective study,
      150 consecutive patients (mean age, 63 +/- 8 years; 132 men and 18 women)
      undergoing coronary artery bypass grafting were randomly assigned to one of three
      groups. Two groups received different doses of intravenous amiodarone (group I,
      300-mg bolus and 20 mg x kg(-1) x day(-1) for 3 days; group II, 150-mg bolus and
      10 mg x kg(-1) x day(-1) for 3 days) after aortic cross-clamping and one group,
      placebo (group III). Continuous electrocardiographic online monitoring was
      performed for 10 days. Arrhythmias were analyzed with respect to type, frequency,
      duration, and clinical relevance. RESULTS: New onset of atrial fibrillation
      occurred in 24% of patients in group I, 28% in group II, and 34% in group III (p
      = not significant). Atrial fibrillation with a rapid ventricular response (>120
      beats per minute) was significantly more frequent in the control group (group I,
      14%; group II, 24%; group III, 32%; p < 0.05, group I versus group III) and
      appeared significantly earlier (group I, day 4.3 +/- 2.5; group II, day 4.8 +/-
      2.9; group III, day 2.6 +/- 1.3; p < 0.05, group III versus groups I and II).
      Temporary atrial pacing because of bradycardia (<60 beats per minute) was
      necessary significantly more often in group I (group I, 48%; group II, 40%; group
      III, 28%; p < 0.05, group I versus group III). Early mortality rate (group I, 4%;
      group II, 2%; group III, 4%), rate of perioperative complications (group I, 14%;
      group II, 20%; group III, 14%), and duration of hospital stay (group I, 14.0
      days; group II, 14.4 days; group III, 14.7 days) were not different between
      groups. CONCLUSIONS: Intraoperative prophylactic use of amiodarone does not
      prevent new onset of atrial fibrillation in patients undergoing coronary artery
      bypass grafting and had no effect on outcome. Therefore, intraoperative
      prophylactic treatment with amiodarone at the tested doses does not appear to be
      justified.

PMID- 10881806
TI  - Potassium channel openers: are they effective as pretreatment or additives to
      cardioplegia?
AB  - BACKGROUND: This study was designed to test the hypothesis that the potassium
      channel opener pinacidil (Pin) as a pretreatment (PT) agent or additive to St.
      Thomas' solution (StT) could enhance myocardial protection. METHODS: In a
      parabiotic rabbit Langendorff model, 36 hearts underwent global normothermic
      ischemia (1 hour) followed by reperfusion (30 minutes). Cardioplegia (50 mL,
      every 20 minutes) consisted of: StT; PinPT/StT, where Pin PT preceded StT arrest;
      Pin alone; Pin in StT (Pin/StT); and Pin in low potassium StT. Systolic function
      after reperfusion (percent recovery of developed pressure) and compliance
      (diastolic slope from pressure-volume relationship) were measured. RESULTS: There
      was no significant difference between StT and PinPT/StT in percent recovery of
      developed pressure (51.54% +/- 3.5%, 42.17% +/- 4.0%, respectively) or
      compliance. Likewise, no significant differences occurred between Pin, StT,
      Pin/StT, and Pin in low potassium StT in percent recovery of developed pressure
      (58.99% +/- 4.8%, 51.54% +/- 3.5%, 53.09% +/- 3.2%, 66.43% +/- 7.3%,
      respectively) or compliance. CONCLUSIONS: Pin is as effective a cardioplegic
      agent as StT; however, its use as a pretreatment or additive to traditional and
      Pin in low potassium StT provided no additional benefit in functional recovery.

PMID- 10881807
TI  - Effects of left ventricular assist devices on outcomes in patients undergoing
      heart transplantation.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) are increasingly being used
      to "bridge" patients to heart transplantation. METHODS: Data from 40 consecutive
      status 1 heart transplantation patients treated with intravenous inotrope therapy
      (n = 20) or the HeartMate LVAD (n = 20) were retrospectively analyzed. RESULTS:
      Baseline clinical characteristics were similar in the two groups. At the time of
      transplantation, LVAD patients had significantly higher blood pressure and sodium
      with significantly lower blood urea nitrogen and creatinine. After
      transplantation, renal failure (52.6% versus 16.7%) and right heart failure
      (31.6% versus 5.6%) occurred more frequently (p < 0.05) in the inotrope group.
      Six-month survival after transplantation did not significantly differ in the
      inotrope or LVAD groups (73.7% versus 88.9%) but event-free survival was
      significantly (p < 0.05) lower in the inotrope group (15.8% versus 55.6%). Total
      hospital charges were significantly lower in the inotrope group ($213,860 +/-
      $107,560 versus $342,620 +/- $104,420), but average daily hospital charges were
      not different ($3,990 +/- $1,300 versus $4,130 +/- $2,050). CONCLUSIONS: Status 1
      heart transplant patients treated with an LVAD as opposed to inotrope therapy
      have improved clinical and metabolic function at the time of transplant and
      improved survival to 6 months after transplant without major complications. Total
      costs are higher in the LVAD patients but average daily costs are similar.

PMID- 10881808
TI  - Controlled clinical trial of a novel hemostatic agent in cardiac surgery. The
      Fusion Matrix Study Group.
AB  - BACKGROUND: We performed a prospective randomized trial to compare FloSeal Matrix
      (Fusion Medical Technologies, Inc, Mountain View, CA), a gelatin-based hemostatic
      sealant, with Gelfoam-Thrombin (Gelfoam, Pharmacia and Upjohn, Kalamazoo, MI;
      Thrombin, Gentrac Inc, Middeton, WI) (control group) to control perioperative
      bleeding. METHODS: A total of 93 patients undergoing cardiac operations were
      randomized into the FloSeal or control group after standard surgical means to
      control bleeding had failed. The bleeding site was evaluated at 1, 2, 3, 6, and
      10 minutes after applying the hemostatic agent. If bleeding stopped within 10
      minutes, the application was considered to be successful. In the case of a
      failure, the surgeon could use any means preferred (except FloSeal) to achieve
      hemostasis. All bleeding sites in a patient were treated with the hemostatic
      agent to which the patient was randomized. Follow-up evaluation was performed at
      12 to 36 hours and 6 to 8 weeks after operation. RESULTS: FloSeal stopped
      bleeding in 94% of the patients (first bleeding site only) within 10 minutes,
      compared to 60% in the control group (p = 0.001). At 3 minutes, successful
      hemostasis was achieved in 72% of the FloSeal group compared with 23% in the
      control group (p = 0.0001). There was no difference in the adverse event profile
      between the two groups. CONCLUSIONS: FloSeal Matrix demonstrated efficacy
      superior to that of Gelfoam-Thrombin and had a safety profile similar to that of
      Gelfoam-Thrombin when used as a topical hemostatic agent during cardiac surgery
      procedures.

PMID- 10881809
TI  - Beating heart versus conventional single-vessel reoperative coronary artery
      bypass.
AB  - BACKGROUND: Reoperative (redo) coronary artery bypass grafting (CABG) with
      cardiopulmonary bypass (on-pump) is associated with a higher morbidity and
      mortality than first-time CABG. It is unknown, however, whether CABG without
      cardiopulmonary bypass (off-pump) may yield an improved clinical outcome over
      conventional on-pump redo CABG. METHODS: We compared the perioperative outcomes
      of patients with single-vessel disease who underwent on-pump (n = 41) versus off
      pump (n = 91) redo CABG between April 1992 and July 1999. The two groups were
      similar with respect to baseline characteristics and risk stratification: mean
      Parsonnet scores were 26 +/- 9 for on-pump versus 24 +/- 8 for off-pump patients
      (p = nonsignificant). RESULTS: On-pump redo patients had a higher rate of
      postoperative transfusions (58% on-pump versus 27% off-pump, p = 0.001),
      prolonged ventilatory support (17% on-pump versus 4% off-pump, p = 0.03), and a
      higher rate of postoperative atrial fibrillation (29% on-pump versus 14% off
      pump, p = 0.04). On-pump redo CABG was also associated with prolonged
      postoperative length of stay (8 +/- 4 days on-pump versus 5 +/- 2 days off-pump,
      p < 0.001). In-hospital mortality was significantly higher in on-pump than in off
      pump patients (10% versus 1%, p = 0.03). CONCLUSIONS: Single-vessel off-pump redo
      CABG can be performed safely with a lower operative morbidity and mortality than
      on-pump CABG and an abbreviated hospital stay compared with conventional on-pump
      redo CABG.

PMID- 10881810
TI  - Early onset prosthetic valve endocarditis: the Cleveland Clinic experience 1992
      1997.
AB  - BACKGROUND: We reviewed all cases of early onset prosthetic valve endocarditis
      (EO-PVE) occurring less than 12 months after valve operation among 7,043 patients
      undergoing heart valve replacements or repairs at The Cleveland Clinic between
      1992 and 1997. METHODS: Cases were defined by the Duke criteria and identified
      through prospective surveillance. RESULTS: Seventy-seven cases of EO-PVE were
      identified (1 per 100 procedures), and during the study period the incidence of
      EO-PVE decreased from 1.5% (1992 to 1994) to 0.7% (1995 to 1997) (p < 0.01). The
      incidence of EO-PVE for rings (0.2%; 4 of 1,992) was significantly lower than for
      mechanical (1.6%; 28 of 1,731) and bioprosthetic valves (1.1%; 41 of 3,320) (p <
      0.001). The incidence of EO-PVE was also significantly lower for mitral valve
      versus aortic valve surgeries (0.6% versus 1.4%, p < 0.001). The most common
      pathogens causing EO-PVE were coagulase-negative staphylococci (52%), fungi
      (13%), Staphylococcus aureus (10%), and enterococci (8%). Patients undergoing
      combined surgical and medical treatment of EO-PVE had a significantly higher 30
      day, 2-year, and 3-year survival than medically treated patients, although
      patients judged to be too ill to survive surgery accounted for two-thirds of the
      patients treated medically. CONCLUSIONS: There is a 1% incidence rate of EO-PVE
      among patients undergoing valve operations at our institution, usually caused by
      coagulase-negative staphylococci, and combined surgical and medical treatment is
      associated with improved survival compared with medical treatment alone.

PMID- 10881811
TI  - Cardioplegia-induced cell swelling: prevention by normothermic infusion.
AB  - BACKGROUND: Previous work has shown significant swelling of isolated rabbit
      myocytes exposed to cold hyperkalemic cardioplegia; however, the effect of warm
      hyperkalemic cardioplegia on myocyte volume is unknown. This study examined the
      effect of warm hyperkalemic cardioplegia (St. Thomas' solution) on myocyte
      volume. METHODS: Myocytes were enzymatically isolated and placed on an inverted
      video microscope. Tyrode's solution (37 degrees C) was infused for 10 minutes to
      establish baseline cell volumes. Subsequently, either the control Tyrode's or St.
      Thomas' was infused either at 37 degrees C and 9 degrees C respectively (n = 5
      for all groups) for 20 minutes, followed by a 30-minute reperfusion with 37
      degrees C Tyrode's. Cell volume was determined from cell images captured every 5
      minutes. RESULTS: Myocyte swelling occurred rapidly on exposure to cold St.
      Thomas' solution to a maximum of 9.8 +/- 2.1% (p < 0.001). In contrast, myocytes
      exposed to warm cardioplegia did not show any volume changes during exposure to
      cardioplegia. However, upon reexposure to Tyrode's, these cells showed shrinkage
      below their baseline volume (p < 0.001). CONCLUSIONS: The cell swelling
      associated with hypothermic cardioplegia is prevented by normothermic infusion.

PMID- 10881812
TI  - Minimal damage during endoscopic latissimus dorsi muscle mobilization with the
      harmonic scalpel.
AB  - BACKGROUND: To reduce wound-related complications, a video-assisted surgical
      technique has been adopted for the mobilization of the latissimus dorsi muscle.
      We postulated that thermal damage to the muscle might be minimized by using a
      Harmonic Scalpel instead of electrocautery during this procedure. METHODS: Canine
      latissimus dorsi muscles were mobilized through a small incision, assisted by a
      videoscope. In 6 dogs, dissection with electrocautery was used to mobilize the
      latissimus dorsi muscle. In 6 other dogs, the Harmonic Scalpel was used. We
      compared operation times, wound infection rates, histologic changes in the
      muscles, and ease of handling between these groups. RESULTS: The operation time
      was significantly shorter in the Harmonic Scalpel group than in the
      electrocautery group (61.5 versus 106.5 minutes, p = 0.00014). The Harmonic
      Scalpel caused less histologic damage to the mobilized muscles and produced less
      vision-obscuring smoke. CONCLUSIONS: The Harmonic Scalpel shortens the operation,
      minimizes muscle damage, and facilitates the performance of video-assisted
      latissimus dorsi muscle mobilization.

PMID- 10881813
TI  - Pulmonary artery perfusion with protective solution reduces lung injury after
      cardiopulmonary bypass.
AB  - BACKGROUND: The inflammatory response and higher temperature of lung tissue
      during cardiopulmonary bypass can result in lung injury. This study was to
      evaluate the protective effect of pulmonary perfusion with hypothermic
      antiinflammatory solution on lung function after cardiopulmonary bypass. METHODS:
      Twelve adult mongrel dogs were randomly divided into two groups. The procedure
      was carried out through a midline sternotomy, cardiopulmonary bypass was
      established using cannulas placed in the ascending aorta, superior vena cava, and
      right atrium near the entrance of the inferior vena cava. After the ascending
      aorta was clamped and cardioplegic solution infused, the right lung was perfused
      through a cannula placed in the right pulmonary artery with 4 degrees C lactated
      Ringer's solution in the control group (n = 6) and with 4 degrees C protective
      solution in the antiinflammation group (n = 6). Antiinflammatory solution
      consisted of anisodamine, L-arginine, aprotinin, glucose-insulin-potassium, and
      phosphate buffer. Plasma malondialdehyde, white blood cell counts, and lung
      function were measured at different time point before and after cardiopulmonary
      bypass; lung biopsies were also taken. RESULTS: Peak airway pressure increased
      dramatically in the control group after cardiopulmonary bypass when compared with
      the antiinflammation group at four different time points (24 +/- 1, 25 +/- 2, 26
      +/- 2, 27 +/- 2 cm H2O versus 17 +/- 2, 18 +/- 1, 17 +/- 1, 18 +/- 1 cm H2O; all
      p < 0.01). Pulmonary vascular resistance increased significantly in the control
      group than in the antiinflammation group at 5 and 60 minutes after
      cardiopulmonary bypass (1,282 +/- 62 dynes x s x cm(-5) versus 845 +/- 86 dynes x
      s x cm(-5) and 1,269 +/- 124 dynes x s x cm(-5) versus 852 +/- 149 dynes x s x
      cm(-5), p < 0.05). Right pulmonary venous oxygen tension (PvO2) in the
      antiinflammation group was higher than in the control group at 60 minutes after
      cardiopulmonary bypass (628 +/- 33.3 mm Hg versus 393 +/- 85.9 mm Hg, p < 0.05).
      The ratio of white blood cells in the right atrial and the right pulmonary venous
      blood was lower in the antiinflammation group than in the control group at 5
      minutes after the clamp was removed (p < 0.05). Malondialdehyde were lower in the
      antiinflammation group at 5 and 90 minutes after the clamp was removed (p < 0.01
      and p < 0.05, respectively). Histologic examination revealed that the left lung
      from both groups had marked intraalveolar edema and abundant intraalveolar
      neutrophils, whereas the right lung in the control group showed moderate injury
      and the antiinflammation group had normal pulmonary parenchyma. CONCLUSIONS:
      Pulmonary artery perfusion using hypothermic protective solution can reduce lung
      injury after cardiopulmonary bypass.

PMID- 10881814
TI  - The effect of sizing on the hydrodynamic parameters of the Medtronic freestyle
      valve in vitro.
AB  - BACKGROUND: An in vitro model has been established to investigate the effect of
      sizing on the hydrodynamic characteristics and leaflet motion of the Medtronic
      Freestyle valve. METHODS: The valves were tested in fresh porcine aortic roots.
      Two or three different sizes of valves were implanted in the same aortic root one
      after the other. The compliance of the fresh aortic and the composite roots was
      measured in the pressure range of 0 to 120 mm Hg, and the composite roots were
      then tested in a pulsatile flow simulator. The transvalvular gradient and degree
      of regurgitation were measured and the effective orifice area and performance
      index were calculated. Leaflet motion was recorded on video. RESULTS: The fresh
      aortic roots dilated by average 39.4% as the hydrostatic pressure rose from 0 to
      120 mm Hg. Implantation of the Medtronic Freestyle valve did not change the
      distensibility of the aortic root significantly. The sizing protocol did not
      affect significantly the hydrodynamic performance. However, a significantly lower
      open leaflet bending deformation was found in the undersized valves.
      Regurgitation was found only at 2-mm undersized valves. CONCLUSIONS: Leaflet
      motion of the Medtronic Freestyle valve in vitro was best if 1 mm undersized, and
      this may be beneficial to long-term durability.

PMID- 10881815
TI  - Angiogenesis in ischemic human myocardium: clinical results after 3 years.
AB  - BACKGROUND: Using the human fibroblast growth factor we could already demonstrate
      the induction of neoangiogenesis in the ischemic human myocardium. METHODS: Forty
      patients, who were undergoing elective coronary artery bypass grafting were
      randomly selected and allotted either to a treatment or a control group. In 20
      patients (study group) fibroblast growth factor was injected directly into the
      myocardium, close to the left anterior descending coronary artery. The control
      group comprised 20 patients who had been injected with heat denatured fibroblast
      growth factor. The 3-year follow-up consisted of a clinical examination,
      echocardiography, and selective imaging of the internal mammary artery bypass
      using angiography. RESULTS: As with the early results, a dense new capillary
      network could be demonstrated angiographically in the region where the factor had
      been injected. Echocardiography showed an increase in the left ventricular
      ejection fraction in the study group. We also found a more pronounced improvement
      in the clinical appearance of the patients with fibroblast growth factor.
      CONCLUSIONS: Fibroblast growth factor, in addition to operative myocardial
      revascularization, may be the appropriate treatment for patients with peripheral
      stenosis or diffuse coronary arteriosclerosis. It is necessary to confirm these
      results in further studies on a larger group of patients.

PMID- 10881816
TI  - Effects of single dose, postinduction dexamethasone on recovery after cardiac
      surgery.
AB  - BACKGROUND: Corticosteroids have been recommended to facilitate rapid recovery
      after cardiac surgery. We previously reported that dexamethasone given after
      induction of anesthesia decreases the incidence of postoperative shivering. We
      performed a post hoc analysis of the data obtained during that study, focusing on
      secondary outcomes. METHODS: A total of 235 adult patients undergoing elective
      coronary or valvular heart surgery were randomized to receive dexamethasone 0.6
      mg/kg or placebo after induction of anesthesia. Patients who had
      pharmacologically treated diabetes mellitus, had hypersensitivity to
      dexamethasone, or were receiving treatment with corticosteroids were excluded.
      RESULTS: We found that, compared with placebo, patients receiving dexamethasone
      were more likely to remain tracheally intubated for 6 hours or less (26.4% vs
      10.0%, p = 0.020) and had a lower incidence of early postoperative fever (20.2%
      vs 36.8%, p = 0.009) and new-onset atrial fibrillation during the first 3 days
      postoperatively (18.9% vs 32.3%, p = 0.027). However, we could not demonstrate a
      statistical difference in the intensive care unit or hospital length of stay, or
      in overall morbidity and mortality. The dexamethasone-treated patients were also
      more likely to have a higher blood glucose on admission to the intensive care
      unit (186 mg/dL vs 143 mg/dL, p = 0.012). CONCLUSIONS: Dexamethasone facilitates
      early tracheal extubation and is associated with a lower incidence of early
      postoperative fever and new-onset atrial fibrillation. Apart from a treatable
      decreased glucose tolerance, dexamethasone treatment was not shown to affect
      morbidity or mortality significantly.

PMID- 10881817
TI  - Hydrodynamics of aortic arch vessels during perfusion through the right
      subclavian artery.
AB  - BACKGROUND: Performing subclavian artery cannulation in patients with an
      atherosclerotic ascending aorta or acute aortic dissection is of growing
      interest. To increase knowledge about pressure and flow distribution in the arch
      vessels, we investigated the in vitro perfusion characteristics in right
      subclavian artery cannulation. METHODS: Pressures and flow rates in the arch
      vessels of an aortic arch model were measured during perfusion through the right
      subclavian artery with different geometries and varying flow rates. Flow
      visualization was performed by laser light. RESULTS: In normal subclavian artery
      geometries, pressure and flow showed a significant increase in only the right
      common carotid artery (8 mm Hg and 25.5 mL/min, respectively, at 5.5 L/min pump
      flow). In cases of 50% stenosis at the right subclavian artery origin, a
      reduction of pressure and flow (6 mm Hg and 22.5 mL/min, respectively, at 5.5
      L/min pump flow) in the right carotid artery caused by a suction effect was
      observed. CONCLUSIONS: Right subclavian artery cannulation provides a valuable
      alternative for ascending aortic cannulation, enabling nearly balanced arch
      vessel perfusion. Stenosis at the right subclavian artery origin carries the
      potential risk of slightly reduced perfusion of the right common carotid artery
      with questionable clinical relevance.

PMID- 10881818
TI  - Reduced neuropsychological dysfunction using epiaortic echocardiography and the
      exclusive Y graft.
AB  - BACKGROUND: To examine the effect of screening the aorta for atheroma before
      aortic manipulation and use of exclusive Y graft revascularization on the
      incidence of neuropsychological dysfunction after coronary artery bypass.
      METHODS: Aortic atheroma was detected using epiaortic and transesophageal
      echocardiography. Atheroma avoidance was facilitated by use of the exclusive Y
      graft technique, which has no aortic coronary anastomoses. In the control group
      aortic atheroma was assessed by manual palpation, and we attempted to avoid any
      atheroma detected. In this group we also used aorta-coronary grafts. Transcranial
      Doppler imaging of the right middle cerebral artery was used to detect cerebral
      microemboli. Neuropsychological dysfunction was defined as a 20% or more decline
      in score for at least 20% of a neuropsychometric battery of ten tests for each
      patient. RESULTS: Late dysfunction at 57 +/- 2 days postoperatively in the
      control group was 38.1% and in the echo/Y group was 3.8% (p' = 0.012).
      Microemboli detected by transcranial Doppler imaging during periods of aortic
      manipulation was greater for those with late dysfunction (5.2 +/- 3.0 compared
      with 0.5 +/- 0.2) (p' = 0.018). No clinical strokes occurred in either group.
      CONCLUSIONS: The combined techniques of epiaortic screening and exclusive Y graft
      for coronary artery bypass operations resulted in a low incidence of late
      neuropsychological dysfunction.

PMID- 10881819
TI  - Impairment of aortal tone by no flow-reflow conditions and its partial
      amelioration by mannitol.
AB  - BACKGROUND: Although postischemic cardiac or pulmonary dysfunction can relate to
      the impact of remotely generated oxygen stress mediators on the heart, their
      direct effect on the vascular bed remains unresolved. Thus, we tested these
      remote effects in an ex-vivo double organ model. METHODS: After stabilization
      With Krebs-Henseleit solution, isolated rat livers were either perfused or made
      ischemic for 2 hours. Aortic rings were stabilized, immersed in postischemic
      liver perfusates and their functions were tested. Some organs originated from
      donors fed with tungstate, whereas others had mannitol (0.25 g/kg) in the buffer.
      RESULTS: Incubation of aortic rings with postischemic hepatic effluent resulted
      in protracted contraction. Spasm was slightly lesser when the livers were
      pretreated with tungstate or exposed to mannitol, but worse in pretreated rings.
      The return to basal tone was abrupt in all ischemia-reperfusion aortae. The
      response of the rings to phenylephrine under the influence of the ischemia
      reperfusion hepatic effluent was deficient. Mannitol prevented most abnormal
      responses. CONCLUSIONS: Aortal tone impairment can occur by direct influence of
      the ischemia-reperfusion liver. It cannot be attributed entirely to xanthine
      oxidase, but also to other hepatic-released factors.

PMID- 10881820
TI  - Dynamic cardiomyoplasty: long-term clinical results in patients with dilated
      cardiomyopathy.
AB  - BACKGROUND: Dynamic cardiomyoplasty has been considered to be an effective method
      of surgical treatment of patients with end-stage heart failure, and is an
      alternative to heart transplantation. METHODS: We critically evaluated the long
      term course of 52 patients with dilated cardiomyopathy who underwent dynamic
      cardiomyoplasty and were followed-up for up to 110 months. RESULTS: Dilated
      cardiomyopathy was due to undetermined cause in 42 patients (80.8%), Chagas
      disease in 8 (15.4%), viral infection in 1 (1.9%), and peripartum cardiomyopathy
      in 1 (1.9%). In the nonchagasic group the survival rates were 79.5% +/- 6.1%,
      67.8% +/- 7.1%, 53.7% +/- 8.3%, 49.9% +/- 8.3%, 14.9% +/- 12.2%, and 14.9% +/-
      12.2%, respectively, at 12, 24, 48, 60, 80 and 110 months of follow-up. In the
      chagasic patients the survival rates were 37.5% +/- 17.1%, 12.5% +/- 11.7%, 12.5%
      +/- 11.7% and 0%, respectively, at 12, 24, 48, and 60 months of follow-up, making
      chagasic cardiomyopathy a possible contraindication for dynamic cardiomyoplasty.
      CONCLUSIONS: There was no correlation between the clinical improvement and
      hemodynamic data. Ventricular fibrillation was a frequent cause of immediate and
      late death, suggesting the need for prophylactic use of antiarrhythmic drugs or
      implantable cardioverter/ defibrillators.

PMID- 10881821
TI  - Surgery for active culture-positive endocarditis: determinants of early and late
      outcome.
AB  - BACKGROUND: The purpose of this study was to describe a single unit experience in
      the surgical treatment of active culture-positive endocarditis and identify
      determinants of early and late outcome. PATIENTS AND METHODS: One hundred
      eighteen consecutive patients with positive blood culture up to 3 weeks before
      operation (or positive valve culture) and macroscopic evidence of lesions typical
      for endocarditis, undergoing operation between January 1973 and December 1996 in
      Southampton, were evaluated. The aortic valve was infected in 53 (48.9%), the
      mitral in 46 (39%), both aortic and mitral in 12 (10.1%), the tricuspid in 4
      (3.9%), and the pulmonary valve in 3 (2.5%). Native valve endocarditis was
      present in 83 (70.3%) and prosthetic valve endocarditis in 35 (29.7%).
      Streptococci and staphylococci were the most common pathogens. Mean follow-up was
      5.6 years (range, 0 to 25 years). RESULTS: Operative mortality was 7.6% (9
      patients). Endocarditis recurred in 8 (6.7%). A reoperation was required in 12
      (10.2%). There was 24 late deaths, 17 of them cardiac. Actuarial freedom from
      recurrent endocarditis, reoperation, late cardiac death, and long-term survival
      at 10 years were 85.9%, 87.2%, 85.2%, and 73.1%, respectively. On multiple
      regression analysis the following were independent adverse predictors: pulmonary
      edema (p = 0.007) and impaired left ventricular function (p = 0.02) for operative
      mortality; prosthetic valve endocarditis (p = 0.01) for recurrent infection;
      myocardial invasion by the infection (p = 0.01) and reoperation (p = 0.04) for
      late cardiac death; and coagulase-negative staphylococcus (p = 0.02), annular
      abscess (p = 0.02), and longer intensive care unit stay (p = 0.02) for long-term
      survival. CONCLUSIONS: Operation for active culture-positive endocarditis carries
      an acceptable mortality. Freedom from recurrent infection, reoperation, and long
      term survival are satisfactory. In our data, patients' hemodynamic status at
      operation was the major determinant of operative mortality. Prosthetic valve
      endocarditis, coagulase-negative staphylococcus, and annular or myocardial
      infectious invasion were the critical adverse determinants of late outcome.

PMID- 10881822
TI  - Anterior intercostal nerve damage after coronary artery bypass graft surgery with
      use of internal thoracic artery graft.
AB  - BACKGROUND: The prevalence of intercostal nerve damage associated with coronary
      artery bypass graft-internal thoracic (mammary) artery surgery is unknown.
      METHODS: A total of 37 consecutive patients with coronary artery bypass graft
      surgery (all with left internal thoracic artery graft) who were attending a
      cardiac-related exercise program underwent a thorough examination. Nerve damage
      was considered to be "definite" in the presence of two consistent and well
      demarcated sensory abnormalities over the anterior chest wall within the T1 to T6
      anterior intercostal nerve territory, and was considered "possible" in the
      presence of one such abnormality. RESULTS: Definite nerve damage was detected in
      73% of the subjects, and possible nerve damage was found in another 11% at the
      site of internal thoracic artery harvesting. Protracted postoperative pain or
      unpleasant sensations, usually subsiding by 4 months, were reported by
      recollection by 81% of the subjects. Overall, the prevalence of persistent pain
      in those with definite nerve damage 5 to 28 months after surgery was 15%.
      CONCLUSIONS: Intercostal nerve damage seems to occur in three-quarters of all
      patients undergoing coronary artery bypass graft-internal thoracic artery
      surgery. A significant minority may continue to experience bothersome chronic
      chest wall pain.

PMID- 10881823
TI  - Standard aortic St. Jude valve at 18 years: performance profile and determinants
      of outcome.
AB  - BACKGROUND: The standard St. Jude disc valve has been in use for 20 years and
      remains the dominant mechanical valve of today. With nearly 19 years of follow
      up, the present large series could indicate the performance profile and its
      determinants in the very long term. METHODS: A detailed follow-up was performed
      to a maximum of 18.6 years in 694 patients aged 15 to 83 years who undervent
      aortic valve replacement (AVR) with the standard St. Jude valve during 1980 to
      1993. The Cox regression analysis was used to identify independent determinants
      of outcome in the aortic stenosis (n = 490) and regurgitation (n = 204) groups.
      RESULTS: Overall survival was 58%, 39%, and 37% at 10, 15, and 18 years,
      respectively. Only 12% of deaths (0.60%/ patient-year) were related to the valve
      with a 15-year freedom of 91%. Embolism (1.18%/patient-year) and anticoagulant
      related bleeding (2.24%/patient-year) were the dominant complications with 10
      year/15-year freedoms of 90%/80% and 85%/72%, respectively. Only 24% of bleeding
      events were classified as major. Valve thrombosis occurred in 2 patients
      (0.04%/patient-year): 1 did not receive vitamin K antagonist treatment and
      International Normalized Ratio was below target level in the other. There were no
      mechanical failures. Endocarditis (0.42%/patient-year) and paravalvular leak
      (0.42%/ patient-year) occurred with 15-year freedoms of 92% and 96%,
      respectively, with a relation between the latter (but not the former) and
      preoperative endocarditis in the regurgitation group. Freedom from serious
      complications (2.33%/patient-year) and all complications joined (4.33%/ patient
      year) were 72% and 54%, respectively, at 15 years with a 96% freedom from redo
      AVR (0.36%/patient-year). Age- and heart-related variables were independent risk
      factors for mortality, thromboembolism, bleeding, serious complications, and all
      complications joined. Small valve (19 and 21 mm) adversely affected serious and
      all complications in the regurgitation group. CONCLUSIONS: With a follow-up
      approaching 2 decades and exhibiting a low rate of valve-related deaths,
      acceptable low thrombogenicity, and absence of mechanical failure, the standard
      aortic St. Jude disc valve sets the standard for contemporary mechanical valves.

PMID- 10881824
TI  - Pulmonary abnormalities after coronary arterial bypass grafting operation:
      cardiopulmonary bypass versus mechanical stabilization.
AB  - BACKGROUND: Cardiopulmonary bypass has been implicated in causing poor pulmonary
      gas exchange postoperatively in patients undergoing coronary artery bypass
      grafting procedures. This randomized prospective study was conducted to determine
      whether patients undergoing coronary artery bypass grafting operations using
      cardiac stabilization and thereby avoiding cardiopulmonary bypass will have
      improved pulmonary function postoperatively. METHODS: Fifty-eight patients were
      randomized to one of two groups: coronary artery bypass grafting operation with
      stabilization or coronary artery bypass grafting operation with cardiopulmonary
      bypass. Preoperative and postoperative pulmonary gas exchange measurements were
      performed on intubated patients, including the arterial partial pressure of
      oxygen on 100% inspired oxygen, the alveolar-arterial oxygen gradient, and
      pulmonary shunt. Static and dynamic lung compliance measurements were performed
      postoperatively. Hemodynamic variables (including creatine kinase-MB and troponin
      levels), intubation time, postoperative bleeding, and blood transfusions were
      compared. RESULTS: Both study groups had a large decrease in arterial partial
      pressure of oxygen on 100% inspired oxygen (p < 0.0001) and a significant
      postoperative increase in the alveolar-arterial oxygen gradient (p < 0.0001).
      There was no statistical difference in the postoperative gas exchange between the
      two groups; however, the postoperative pulmonary shunt was significantly better
      in the stabilization group (24% versus 31%, p = 0.03). The patients were
      extubated in the intensive care unit earlier in the stabilization group (8.2
      hours versus 9.2 hours, not significant). The mean static and dynamic lung
      compliance postoperatively was lower in the stabilization group, although not
      statistically significant (p = 0.06). CONCLUSIONS: Coronary artery bypass
      grafting operation using cardiac stabilization technique is safe and avoids the
      risk of cardiopulmonary bypass. The pulmonary gas exchange postoperatively is
      comparable to standard cardiopulmonary bypass procedures, but a reduced
      postoperative pulmonary shunt was seen in the stabilization group.

PMID- 10881825
TI  - Stroke in octogenarians undergoing coronary artery surgery with and without
      cardiopulmonary bypass.
AB  - BACKGROUND: Myocardial revascularization in elderly patients is associated with a
      morbidity and a mortality substantially higher than those observed in younger
      patients. The aim of this study was to analyze the potential benefits of coronary
      artery bypass grafting without cardiopulmonary bypass (CPB) for octogenarians.
      METHODS: Of 269 octogenarians who underwent coronary artery bypass grafting at
      our institution between January 1995 and May 1999, 172 had the operation with CPB
      (CPB group) and 97, without CPB (off-pump group). Revascularization of the
      circumflex system or right coronary artery were not considered contraindications
      to off-pump grafting. Demographic data, preoperative risk factors, comorbid
      conditions, angiographic findings, postoperative complications, and outcomes were
      compared. RESULTS: The groups were comparable for age, sex, Canadian
      Cardiovascular Society class, operative priority (elective, urgent, or emergent),
      preoperative risk factors, and left ventricular ejection fraction. A
      significantly higher proportion of reoperations was observed in the off-pump
      cohort (16 of 97, 16.5%) compared with the CPB cohort (8 of 172, 4.7%) (p =
      0.002). There was a trend toward a higher graft-patient ratio in the CPB group
      (3.3 versus 1.8; p = not significant). Freedom from postoperative complications
      was significantly higher in the off-pump group than in the CPB group (83 of 97,
      85.6%, versus 129 of 172, 75%; p = 0.04). The incidence of stroke was 0% in the
      off-pump cohort compared with 9.3% (16 of 172) in the CPB cohort (p < 0.0005).
      Although there was a trend toward higher 30-day and risk-adjusted mortality rates
      in the off-pump group than in the CPB group (10.3% versus 5.2% and 2.8% versus
      1.8%, respectively), the differences were not significant. The length of
      hospitalization was slightly lower in the off-pump group (9.1 versus 10.8 days; p
      = not significant). CONCLUSIONS: This investigation suggests that patients 80
      years of age and older undergoing off-pump coronary artery bypass grafting can
      experience significantly lower rates of perioperative stroke and overall
      complications compared with those undergoing the same procedure with CPB,
      although a trend toward higher mortality rates was observed in the off-pump
      group.

PMID- 10881826
TI  - Extracorporeal membrane oxygenation for infant postcardiotomy support:
      significance of shunt management.
AB  - BACKGROUND: After repair of complex congenital heart defects in infants and
      children, postcardiotomy cardiac failure requiring temporary circulatory support
      can occur. This is usually accomplished with the use of extracorporeal membrane
      oxygenation (ECMO). ECMO management of patients with single-ventricle physiology
      and aorto-pulmonary shunts can be particularly challenging. We retrospectively
      reviewed our experience with postcardiotomy support with particular attention to
      those children with single-ventricle palliation. METHODS: Thirty-five consecutive
      children (age 1 to 820 days, median 19 days) out of 1,020 patients (3.4%)
      required mechanical support (ECMO) after repair of congenital cardiac lesions
      from February 1994 to April 1999. Twenty-five patients underwent two ventricle
      repairs and 10 patients had single-ventricle palliation. Various parameters
      analyzed included strategies of shunt management, presence of presupport cardiac
      arrest, and timing of support initiation. RESULTS: Overall hospital survival for
      these 35 patients was 61%. There were four additional late deaths. Hospital
      survival was the same for those patients in whom support was initiated for
      failure to wean from cardiopulmonary bypass in the operating room versus those
      patients in whom support was initiated after successful separation from
      cardiopulmonary bypass (6 of 10 vs 15 of 25 or 60% survival). In those patients
      with shunt-dependent pulmonary circulation, survival was significantly improved
      in those patients in which the aorto-pulmonary shunt was left open (4 of 5 with
      open shunt vs 0 of 4 with occluded shunt (p = 0.048). CONCLUSIONS: The ability to
      readily implement postcardiotomy support is vital to the management of children
      with complex congenital cardiac disease. Overall survival can be quite
      satisfactory if support is employed in a rational and expedient manner. In
      patients with single-ventricle physiology and aorto-pulmonary shunts, leaving the
      shunt open during the period of support can result in markedly improved outcomes.

PMID- 10881827
TI  - Free hemoglobin impairs cardiac function in neonatal rabbit hearts.
AB  - BACKGROUND: Hemolysis caused by cardiopulmonary bypass causes renal dysfunction
      and other organ failure presumably by superoxide production catalyzed by iron
      derived from free hemoglobin (f-Hb). It might also impair cardiac function by the
      same mechanism, especially in the ischemia-reperfusion period and in neonates
      where serum antioxidant activity is lower than adults. METHODS: We evaluated
      effects of f-Hb on cardiac function with or without ischemia and reperfusion
      using a newborn (7 days old) rabbit crystalloid-perfused Langendorff model. After
      baseline measurements, the hearts were divided into the following four groups (8
      hearts per group): (1) those perfused with regular Krebs-Henseleit bicarbonate
      buffer, (2) those perfused 30 minutes with KH buffer containing 1 mg/mL of f-Hb
      obtained from osmotic hemolysis, (3) those subjected to 180 minutes of cold
      global ischemia with infusion of crystalloid cardioplegia and reperfused with
      Krebs-Henseleit buffer, and (4) those subjected to the same ischemia and
      reperfused with Krebs-Henseleit buffer containing 1 mg/mL of f-Hb. The left
      ventricular function (using conductance catheter and isovolumic balloon) and
      coronary flow were measured. RESULTS: Free hemoglobin significantly impaired not
      only left ventricular function but also coronary flow even without ischemia (p <
      0.05). When ischemia and reperfusion were involved, the group reperfused with f
      Hb showed the worst left ventricular function and coronary flow among the groups.
      CONCLUSIONS: This study shows that f-Hb directly impaired cardiac function and
      coronary flow in neonatal hearts especially in ischemia and reperfusion.

PMID- 10881828
TI  - Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in
      children.
AB  - BACKGROUND: A randomized, prospective, double-blind study of 29 children was
      performed to evaluate the hypothesis that dexamethasone administration prior to
      cardiopulmonary bypass would decrease the inflammatory mediator release and
      improve the postoperative clinical course. METHODS: Fifteen children received
      dexamethasone (1 mg/kg intravenously) and 14 (controls) received saline solution
      1 hour prior to CPB. Serial blood analyses for interleukin-6, tumor necrosis
      factor-alpha, complement component C3a, and absolute neutrophil count were
      performed. Postoperative variables evaluated included temperature, supplemental
      fluids, alveolar-arterial oxygen gradient, and days of mechanical ventilation.
      RESULTS: Dexamethasone caused an eightfold decrease in interleukin-6 levels and a
      greater than threefold decrease in tumor necrosis factor-alpha levels after CPB
      (p < 0.05). Complement component C3a and absolute neutrophil count were not
      affected by dexamethasone. The mean rectal temperature for the first 24 hours
      postoperatively was significantly lower in the group given dexamethasone than in
      the controls (37.2 degrees +/- 0.4 degrees C versus 37.7 degrees +/- 4 degrees C;
      p = 0.007). Dexamethasone-treated patients required less supplemental fluid
      during the first 48 hours (22 +/- 28 mL/kg versus 47 +/- 34 mL/kg; p = 0.04).
      Compared with controls, dexamethasone-treated children had significantly lower
      alveolar-arterial oxygen gradients during the first 24 hours (144 +/- 108 mm Hg
      versus 214 +/- 118 mm Hg; p = 0.02) and required less mechanical ventilation
      (median duration, 3 days versus 5 days; p = 0.02). CONCLUSIONS: Dexamethasone
      administration prior to CPB in children leads to a reduction in the postbypass
      inflammatory response as assessed by cytokine levels and clinical course.

PMID- 10881829
TI  - Transaortic closure of residual intramural ventricular septal defect.
AB  - BACKGROUND: Residual intramural ventricular septal defect is an unusual cause of
      left-to-right shunt after biventricular repair of conotruncal anomalies. It
      results from the insertion of the patch within the trabeculated right ventricular
      free wall related to the ventriculoinfundibular fold creating a communication
      through the intertrabeculated spaces to the right ventricular cavity. This
      complication often leads to unsuccessful reoperations unless the exact mechanism
      of the shunt has been identified. METHODS AND RESULTS: Five patients presented
      with residual intramural ventricular septal defects. Three had double outlet
      right ventricle, one pulmonary atresia with ventricular septal defect, and one
      tetralogy of Fallot. One patient was unsuccessfully reoperated on for closure of
      the residual ventricular septal defect through the right ventricular approach.
      The surgical treatment, which consisted of patch closure of the residual
      intramural ventricular septal defect through aortotomy, was successful in 3
      patients. In the 2 remaining patients the hemodynamically insignificant residual
      intramural ventricular septal defect remained untouched. No mortality or
      morbidity occurred. CONCLUSIONS: Residual intramural ventricular septal defect
      should be suspected in presence of a residual ventricular septal defect after
      biventricular repair of conotruncal anomalies. It is not accessible through
      either atriotomy or right ventriculotomy. The transaortic approach allows an easy
      treatment of this rare complication.

PMID- 10881830
TI  - Systemic pulmonary shunts in neonates: early clinical outcome and choice of
      surgical approach.
AB  - BACKGROUND: Systemic pulmonary shunt remains a major strategy for the palliation
      of cyanotic lesions in neonates despite the associated morbidity and mortality.
      METHODS: Between March 1993 and December 1998, 79 systemic pulmonary shunts were
      performed in 75 neonates with cyanosis and severely reduced pulmonary blood flow.
      The mean age was 11.5 days and the mean weight, 3 kg. All neonates were dependent
      on duct flow and prostaglandin E1 infusion for adequate oxygenation. RESULTS: The
      systemic pulmonary shunt was performed through a right thoracotomy in 36
      patients, left thoracotomy in 6, and median sternotomy in 33 patients. The 30-day
      mortality was 3 patients (4%). Univariate and logistic regression analyses
      revealed a weight less than 2 kg (p = 0.039) and preoperative mechanical
      ventilation (p = 0.008), to be predictors of early mortality, whereas pulmonary
      hypoplasia (p = 0.55), diagnostic group (p = 0.79), shunt size (p = 0.2), and
      surgical approach (p = 0.5) were not. There were seven episodes of shunt-related
      complications that required early intervention. CONCLUSIONS: Systemic pulmonary
      shunt remains an effective palliative measure in cyanotic neonates despite
      specific complications. Both low weight and preoperative ventilation represent
      significant risk factors for early mortality.

PMID- 10881831
TI  - Neonatal repair of Ebstein's anomaly: indications, surgical technique, and medium
      term follow-up.
AB  - BACKGROUND: Ebstein's anomaly in the severely symptomatic neonate is usually
      fatal. Because the mortality for various surgical interventions has been
      prohibitively high, the indications for operation in these critically ill
      neonates are unclear. METHODS: We reviewed our results with biventricular repair
      of three consecutive severely symptomatic neonates (2.8 to 3.2 kg) at our
      institution since 1994. Each had associated complex cardiac pathology, including
      multiple muscular ventricular septal defects (n = 1), pulmonary stenosis with
      functional pulmonary atresia (n = 1), and anatomic pulmonary atresia (n = 1).
      Preoperatively, all infants had severe tricuspid regurgitation, Great Ormond
      Street Ebstein echocardiogram scores greater than 1.3:1 (grade 3 or 4) and
      cardiothoracic ratio greater than 0.85. Two patients were severely cyanotic.
      Hepatic and renal insufficiency with diffuse coagulopathy was present
      preoperatively in two patients. Surgical repair consisted of (1) reconstruction
      of a competent monocuspid tricuspid valve, (2) right ventriculorrhaphy, (3)
      subtotal closure of atrial septal defect (ASD), (4) aggressive reduction
      atrioplasty, and (5) repair of all associated cardiac defects. RESULTS: There
      were no early or late deaths. All patients are currently asymptomatic, without
      medications, and in sinus rhythm. At 5-year follow-up, trivial tricuspid
      regurgitation is present in 1 and mild regurgitation in 2 patients. On the basis
      of these results and review of the current literature, we propose new indications
      for surgical repair in the neonate with Ebstein's anomaly. CONCLUSIONS:
      Biventricular repair of Ebstein's anomaly in the critically ill neonate is
      feasible and medium-term durability of the repair is excellent. Therefore,
      conventional management of these patients should be revised and early surgical
      repair encouraged.

PMID- 10881832
TI  - Apicoaortic conduit for left ventricular outflow tract obstruction: revisited.
AB  - BACKGROUND: We have used a variety of techniques to correct left ventricular
      outflow tract obstructions, including, in the past, placement of an apicoaortic
      valved conduit to bypass the outflow tract. Because the operation was technically
      difficult, it had fallen into disuse. Recently, we used a simplified
      transthoracic approach to implant apicoaortic conduits in 7 patients with complex
      lesions of the left ventricular outflow tract. METHODS: The thoracic cavity was
      entered through the fifth intercostal space in all 7 patients. The distal end of
      the valve-containing conduit was attached to the aorta with continuous 3-0 or 4-0
      polypropylene sutures after incising the pleura over the distal descending aorta.
      The pericardium was opened to expose the left ventricular apex, which was cored
      so that the proximal end of the conduit could be inserted into the left
      ventricular cavity. RESULTS: Five of the patients recovered completely. The 2
      patients who died had severe heart disease and multiple comorbidities.
      CONCLUSIONS: The transthoracic approach gives direct access to the descending
      aorta and avoids a redo sternotomy. The technique, which is simple to perform,
      does not compromise major coronary arteries, the conduction system, or other
      valves; and may be useful in patients who are not good candidates for other, more
      conventional procedures.

PMID- 10881833
TI  - S-100 after correction of congenital heart defects in neonates: is it a reliable
      marker for cerebral damage?
AB  - BACKGROUND: Newborns undergoing cardiac operation may acquire some extent of
      neuronal damage. An early diagnosis is especially hard regarding neonates. In the
      past years, S-100 has been widely discussed as a marker revealing perioperative
      damage to the brain. METHODS: Sequential blood samples from 33 neonates
      undergoing repair of congenital heart disease were taken perioperatively. Samples
      of 12 healthy neonates were taken at birth as a control group. The newborns were
      divided into four groups: cyanotic and acyanotic disease operated on in deep
      hypothermic circulatory arrest, operation without deep hypothermic cardiac
      arrest, and operation without extracorporeal circulation. RESULTS: Even in
      healthy neonates, serum S-100 levels were at 10-fold values compared with adults.
      On admission, S-100 values in the operative groups were similar. During
      extracorporeal circulation, levels rose to a certain degree. Cyanotic newborns
      operated on in deep hypothermic cardiac arrest had significantly higher S-100
      levels compared with acyanotic newborns also operated on in deep hypothermic
      cardiac arrest (p < 0.001). Two newborns who experienced seizures postoperatively
      had the highest absolute S-100 levels. One child with a poor neurologic outcome
      but no seizures did not have different values when compared with her group.
      CONCLUSIONS: In this study, S-100 seemed to be a possible marker for a certain
      degree of neurologic deficit after cardiac operation in neonates, especially
      regarding postoperative seizures. The missing peaks of this protein in one
      newborn with poor neurologic outcome show that it is not possible to exclude
      damage to the brain with normal postoperative values. These results suggest that
      the mechanism of cerebral damage and S-100 release into the blood in neonates
      with a developing central nervous system and blood-brain barrier is not fully
      understood.

PMID- 10881834
TI  - Influence of panel-reactive antibodies on posttransplant outcomes in lung
      transplant recipients.
AB  - BACKGROUND: Panel-reactive antibody (PRA) is used to estimate the degree of
      humoral sensitization in the recipient before transplantation. Although
      pretransplant sensitization is associated with increased complications in other
      solid organ transplant recipients, less is known about the outcome of sensitized
      lung transplant recipients. Therefore, we sought to determine the impact of
      elevated pretransplant PRA on clinical outcomes after lung transplantation.
      METHODS: The records of the first 200 lung transplant operations performed at
      Duke University Medical Center were reviewed. The outcomes of sensitized
      patients, PRA greater than 10% before transplantation (n = 18), were compared
      with the outcomes of nonsensitized patients. RESULTS: Sensitized patients
      experienced a significantly greater number of median ventilator days
      posttransplant (9 +/- 8) as compared with nonsensitized recipients (1 +/- 11; p =
      0.0008). There were no significant differences between the number of episodes of
      acute rejection; however, there was a significantly increased incidence of
      bronchiolitis obliterans syndrome occurring in untreated sensitized recipients
      (56%) versus nonsensitized (23%; p = 0.044). In addition, there was a trend
      towards decreased survival in the sensitized recipients, with a 2-year survival
      of 58% in sensitized recipients as compared with 73% in the nonsensitized
      patients (p = 0.31). CONCLUSIONS: Sensitized lung transplant recipients
      experience more acute and chronic complications after transplantation. These
      patients probably warrant alternative management strategies.

PMID- 10881835
TI  - Thoracoscopic excision of mediastinal bronchogenic cysts: results in 20 cases.
AB  - BACKGROUND: We present our experience with thoracoscopic resection of mediastinal
      bronchogenic cysts in adults. METHODS: From November 1990 to September 1993, 20
      patients with mediastinal bronchogenic cysts were operated on by thoracoscopy.
      The average cyst size was 4.9 cm, and the largest diameter was 10 cm. Ten cysts
      were located in the middle mediastinum and 10 in the posterior mediastinum. Two
      cysts were complicated. RESULTS: Thirteen bronchogenic cysts were resected
      completely by thoracoscopy. We had to convert thoracoscopy into thoracotomy
      because of bleeding in two cases and because of major adhesions to vital
      structures in five cases. There were no operative deaths and no postoperative
      complications. Mean hospital stay was significantly less in the completely
      thoracoscopically treated group. Long-term follow-up (range, 4.5 to 7.5 years)
      showed no late complications and no recurrence. CONCLUSIONS: Preoperative
      complications, intraoperative injuries, and major adhesions to vital structures
      seem to be the only unfavorable conditions to thoracoscopic treatment of
      bronchogenic cysts. This study found encouraging results for thoracoscopic
      excision of mediastinal bronchogenic cysts in selected patients.

PMID- 10881836
TI  - The anatomic distribution of acute cellular rejection in the allograft lung.
AB  - BACKGROUND: Transbronchial lung biopsy (TBLB) is used for routine monitoring and
      diagnosing of acute cellular rejection (ACR) in the lung allograft, and yet the
      optimal anatomic site for lung biopsy has not been investigated. We examined our
      clinical data to clarify the distribution of ACR in the lung allograft monitored
      by TBLB. METHODS: A retrospective case-series study was done reviewing the
      pathology files and slides of TBLB performed on lung allograft recipients. In 73
      patients, transbronchial biopsies were taken from more than one lobe. RESULTS:
      Identical grades of ACR were seen in 33 of 73 (45%) patients, and a single-grade
      difference in ACR was noted 34 of 73 (47%) patients. Six cases demonstrated two
      or more grade differences on biopsies taken from two separate lobes. Among cases
      with different grades of ACR, the "upper" lobes had a higher grade in 35% (14/40)
      and the "lower" lobes had a higher grade in 65% (26/40). CONCLUSIONS: If
      limitations on the site for transbronchial biopsy exist, biopsies of the lower
      lobes appear more informative.

PMID- 10881837
TI  - Apoptosis induced by ischemia and reperfusion in experimental lung
      transplantation.
AB  - BACKGROUND: Apoptosis is a distinct form of single-cell death in response to
      injury. Time course of apoptosis in lung parenchymal cells during posttransplant
      reperfusion and the influence of oxygen content during preservation on apoptosis
      of parenchymal cells are studied. METHODS: Orthotopic syngenic single left lung
      transplantation was performed in male Fischer (F344) rats after 18 hours of cold
      ischemia (n = 5 in all groups). Apoptotic cells were stained by the terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique.
      Strictly TUNEL-positive pneumocytes were counted on anonymized slides by a
      pathologist on 100 fields (x400) per specimen (mean +/- SEM). RESULTS: The peak
      of apoptotic pneumocytes occurred 2 hours after reperfusion (16.8 +/- 2.2
      pneumocytes/100 fields [p/100f]; p = 0.000012 vs controls, lungs fixed after 18
      hours of ischemia), whereas the lowest level of apoptotic pneumocytes was seen in
      lungs fixed after harvest (1.4 +/- 0.51 p/100f) and lungs not undergoing
      reperfusion (2.8 +/- 0.49 p/100f). Four hours after reperfusion, the number of
      apoptotic pneumocytes was lower than 2 hours after reperfusion (13.6 +/- 3.1
      p/100f; p = 0.00032 vs controls), with a further decline at 8 hours (6.4 +/- 1.5
      p/100f) and 12 hours after reperfusion (4.0 + 1.2 p/100f). Interestingly, lungs
      inflated with N2 before storage revealed a significantly lower level of TUNEL
      positive pneumocytes 2 hours after reperfusion (8.8 2.0 p/100f) compared with
      lungs inflated with 100% O2 (p = 0.0052). CONCLUSIONS: Apoptosis of pneumocytes
      after posttransplant lung reperfusion is a very early event. Prolonged
      hypothermic preservation without reperfusion, however, does not lead to an
      elevated rate of apoptotic pneumocytes in lung grafts.

PMID- 10881838
TI  - Thoracoscopic thymectomy in autoimmune myasthesia: results of left-sided
      approach.
AB  - BACKGROUND: We undertook to analyze the results of video-assisted thoracoscopic
      thymectomy through a left-sided approach in patients with autoimmune myasthenia.
      METHODS: Between 1993 and 1997, 31 patients underwent thoracoscopic thymectomy by
      a uniform left-sided approach. There were 8 men and 23 women with a mean age of
      34 +/- 12 years. RESULTS: Preoperative duration of disease was 14.8 +/- 11
      months. There were no operative deaths or major complications. The mean hospital
      stay was 5.2 +/- 2.8 days. Mean follow-up was 39.6 +/- 15 months and was 100%
      complete. At 48 months, remission and improvement rates were 36% and 96%,
      respectively. Shorter duration of symptoms (< 12 months) correlated with improved
      outcome (13 of 13 patients versus 10 of 14 patients; p = 0.036). Age, sex,
      Osserman class, corticosteroid therapy, presence of ectopic thymic tissue, and
      temporary postoperative symptom increase (deterioration) did not affect outcome.
      CONCLUSIONS: Thoracoscopic thymectomy facilitated the goal of early thymectomy.
      Through a left-sided approach, improvement or remission was achieved in more than
      95% of the patients. Thoracoscopic thymectomy should be considered a valid less
      invasive alternative to the most radical open approaches.

PMID- 10881839
TI  - Isolated lung perfusion for patients with unresectable metastases from sarcoma: a
      phase I trial.
AB  - BACKGROUND: In patients with unresectable pulmonary metastases from sarcoma,
      systemic chemotherapy has had limited efficacy possibly because of dose-limiting
      toxicities. Isolated lung perfusion is an alternative method of delivering high
      dose chemotherapy to the lungs while minimizing systemic toxicities. We present
      the results of our Phase I trial of isolated lung perfusion with doxorubicin
      hydrochloride in such a group of patients. METHODS: From May 1995 to June 1997, 8
      patients with unresectable metastases from sarcoma limited to the lungs underwent
      isolated lung perfusion with doxorubicin. A dose-escalation schedule starting at
      40 mg/m2 was used. Seven patients were treated with a dose of 40 mg/m2 or less,
      and 1 patient received 80 mg/m2. Blood, tumor, and normal lung samples were
      obtained at various time points during the operation. Patients were evaluated for
      cardiac, pulmonary, and other toxicities. RESULTS: The doxorubicin concentrations
      in both normal lung and tumor correlated directly with the amount of doxorubicin
      in the perfusate. The tumors took up less doxorubicin than the lung. All patients
      had minimal or undetectable systemic levels of doxorubicin at the conclusion of
      the perfusion. There were no cardiac or other systemic toxicities. In the 7
      patients perfused with 40 mg/m2 or less of doxorubicin, there was a significant
      decrease in the forced expiratory volume in 1 second and a trend toward a
      significant decrease in diffusing capacity. The patient who received 80 mg/m2
      underwent lung scanning postoperatively, and scans showed no ventilation or
      perfusion in the perfused lung. There were no perioperative deaths. Two patients
      are alive with disease, and 6 patients died of disease. The median follow-up is
      11 months and the longest, 31 months. There were no partial or complete
      responses. One patient had stabilization of disease in the perfused lung, whereas
      the lesions in the untreated lung progressed markedly. CONCLUSION: Isolated lung
      perfusion is well tolerated by patients and effectively delivers high doses of
      doxorubicin to the lung and tumor tissues while minimizing systemic toxicities. A
      single dose of 80 mg/m2 resulted in substantial injury to the lung. There were no
      partial or complete responses in patients perfused with doxorubicin at the
      maximum tolerated dose of 40 mg/m2. Isolated lung perfusion remains a model for
      testing new and innovative therapies for metastatic sarcoma.

PMID- 10881840
TI  - Prognostic relevance of Masaoka and Muller-Hermelink classification in patients
      with thymic tumors.
AB  - BACKGROUND: To compare the prognostic relevance of Masaoka and Muller-Hermelink
      classifications. METHODS: We treated 71 patients with thymic tumors at our
      institution between 1980 and 1997. Complete follow-up was achieved in 69 patients
      (97%) with a mean follow up-time of 8.3 years (range, 9 months to 17 years).
      RESULTS: Masaoka stage I was found in 31 patients (44.9%), stage II in 17
      (24.6%), stage III in 19 (27.6%), and stage IV in 2 (2.9%). The 10-year overall
      survival rate was 83.5% for stage I, 100% for stage IIa, 58% for stage IIb, 44%
      for stage III, and 0% for stage IV. The disease-free survival rates were 100%,
      70%, 40%, 38%, and 0%, respectively. Histologic classification according to
      Muller-Hermelink found medullary tumors in 7 patients (10.1%), mixed in 18
      (26.1%), organoid in 14 (20.3%), cortical in 11 (15.9%), well-differentiated
      thymic carcinoma in 14 (20.3%), and endocrine carcinoma in 5 (7.3%), with 10-year
      overall survival rates of 100%, 75%, 92%, 87.5%, 30%, and 0%, respectively, and
      10-year disease-free survival rates of 100%, 100%, 77%, 75%, 37%, and 0%,
      respectively. Medullary, mixed, and well-differentiated organoid tumors were
      correlated with stage I and II, and well-differentiated thymic carcinoma and
      endocrine carcinoma with stage III and IV (p < 0.001). Multivariate analysis
      showed age, gender, myasthenia gravis, and postoperative adjuvant therapy not to
      be significant predictors of overall and disease-free survival after complete
      resection, whereas the Muller-Hermelink and Masaoka classifications were
      independent significant predictors for overall (p < 0.05) and disease-free
      survival (p < 0.004; p < 0.0001). CONCLUSIONS: The consideration of staging and
      histology in thymic tumors has the potential to improve recurrence prediction and
      patient selection for combined treatment modalities.

PMID- 10881842
TI  - Acute injuries of the trachea and major bronchi: importance of early diagnosis.
AB  - BACKGROUND: Tracheobronchial injuries are encountered with increasing frequency
      because of improvements in prehospital care and early initiation of the Advanced
      Trauma Life Support protocol. We review our experience with these injuries with
      the hypothesis that the leading determinant of patient outcome is the time
      interval to diagnosis. METHODS: Patients with tracheobronchial injury were
      identified from the registry of our level 1 trauma center during a 10-year period
      ending December 1997. Clinical presentation, diagnostic evaluation, surgical
      management, and outcome were reviewed. RESULTS: Twenty patients with ten cervical
      tracheal injuries and ten intrathoracic tracheobronchial injuries were treated.
      The mechanism of injury involved blunt trauma in 11 and penetrating trauma in 9.
      All patients underwent surgical debridement and primary repair. Patients with
      isolated airway injuries were discharged home after a mean hospital stay of 6
      days and had no early complications. Three patients had delayed diagnosis (> 24
      hours), and all sustained complications including death (1 patient) and
      multiorgan system failure (2 patients). The overall mortality rate was 15%.
      CONCLUSIONS: Operative management of tracheobronchial injuries can be achieved
      with acceptable mortality. Independent of mechanism or anatomic location of
      injury, delay in diagnosis is the single most important factor influencing
      outcome. Early recognition of tracheobronchial injury and expedient institution
      of appropriate surgical intervention are essential in these potentially lethal
      injuries.

PMID- 10881841
TI  - Pulmonary graft function after long-term preservation of non-heart-beating donor
      lungs.
AB  - BACKGROUND: Critical organ shortage in lung transplantation could be attenuated
      by the use of non-heart-beating donor (NHBD) lungs. In addition, prolonged
      ischemic tolerance of the organs would contribute to the alleviation of organ
      shortage. The aim of this study was to investigate pulmonary graft function of
      NHBD lungs after long-term hypothermic storage. METHODS: Twelve native-bred pigs
      (bodyweight 20 to 30 kg) underwent left lung allotransplantation. In the heart
      beating donor (HBD) group, lungs were harvested immediately after cardiac arrest.
      In the NHBD group, lungs were subjected to a warm ischemic period of 90 minutes
      before harvesting. After a total ischemic time of 19 hours, pulmonary grafts in
      both groups were reperfused and pulmonary graft function was assessed. All values
      were compared with a sham-operated control group. RESULTS: Pulmonary graft
      function in the HBD group was excellent. In the NHBD group, pulmonary gas
      exchange was impaired, but still provided good graft function compared with the
      excellent graft function in the HBD group. Pulmonary vascular resistance was even
      lower in the NHBD group. In the NHBD group, calculated intrapulmonary shunt
      fraction (Qs/Qt) was significantly increased compared with the sham-group.
      Histologic alteration and wet-to-dry ratio did not differ significantly between
      the HBD and NHBD group. CONCLUSIONS: We conclude that NHBD lungs (90 minutes of
      warm ischemic time) have the potential to alleviate organ shortage in lung
      transplantation even after an extended total ischemic time.

PMID- 10881843
TI  - Myocardial infarction caused by a large coronary artery aneurysm.
AB  - A large coronary aneurysm, originating from a side branch of the right coronary
      artery, caused recurrent ischemia resulting in myocardial infarction. Successful
      surgical excision, without concomitant coronary artery bypass grafting, is
      described.

PMID- 10881844
TI  - Congenital intrapericardial aneurysm of the left atrial appendage.
AB  - Congenital aneurysmal dilatation of the left atrial appendage is a rare but
      correctable lesion. It represents a diagnostic dilemma in patients with
      cardiomegaly and is commonly associated with supraventricular arrhythmias and
      life-threatening systemic embolization. We describe the diagnostic evaluation and
      surgical treatment during 1997 of a patient with congenital aneurysmal dilatation
      of the left atrial appendage. The patient was discharged previously from our
      hospital in 1967 with the diagnosis of congenital dilatation of the pulmonary
      artery.

PMID- 10881845
TI  - Impersonation of a ruptured thoracic aneurysm by a transdiaphragmatic pancreatic
      cyst.
AB  - Pancreatic cysts can, in rare cases, expand into the posterior mediastinum and
      may require surgical resection. We present the case of a patient with a thoracic
      aneurysm, in whom the mediastinal involvement of a chronic pancreatic cyst
      masqueraded as a ruptured aneurysm. Surgery was undertaken: first, the initial
      resection and drainage of the thoracic portion of the pseudocyst, and second, a
      thorough cleansing of the entire cyst through median laparotomy 15 days later.

PMID- 10881846
TI  - Videothoracoscopic drainage of mediastinal abscess: an alternative to
      thoracotomy.
AB  - A late-presenting high esophageal perforation that resulted in a massive
      mediastinal abscess and bronchopleural fistula in an elderly moribund patient
      unfit for radical surgery was successfully drained using a videothoracoscopic
      technique.

PMID- 10881847
TI  - Arm ischemia after subclavian flap angioplasty: repair by carotid-subclavian
      bypass.
AB  - Though quite unusual, vascular insufficiency of the arm can occur after ligation
      of the subclavian artery. We describe the ischemic consequences of left
      subclavian interruption in a neonate after subclavian flap angioplasty repair
      (Waldhausen procedure) for coarctation. Subsequent carotid-subclavian artery
      bypass was successful in relieving symptoms.

PMID- 10881848
TI  - Upper limb ischemia after subclavian flap aortoplasty: unusual long-term
      complication.
AB  - Repair of isolated coarctation of the aorta by subclavian flap aortoplasty
      carries the disadvantage of impaired blood supply to the left arm. However,
      ligation of branches of the subclavian artery can be tolerated without manifest
      ischemia of the upper extremity. We report the case of a young man who suffered
      from left upper extremity ischemia 18 years after initial operation. Treatment
      consisted of carotid-subclavian bypass with good outcome. The surgical approach
      of coarctation by subclavian aortoplasty should be reserved for specific cases,
      and if this procedure is performed, ligation of branches of the subclavian artery
      should be minimized to increase inflow into the left brachial artery.

PMID- 10881850
TI  - Thoracoscopic treatment of primary chylopericardium.
AB  - The development of video-assisted thoracoscopy has changed the practice of
      thoracic surgery. This report describes a 20-year-old man who successfully
      underwent thoracoscopic thoracic duct ligation and partial pericardiectomy for
      primary chylopericardium. We recommend a right-sided thoracoscopic approach to
      the thoracic duct in the lower thoracic cavity.

PMID- 10881849
TI  - Chest wall implantation of a mediastinal liposarcoma after thoracoscopy.
AB  - We report a case of mediastinal liposarcoma resected by thoracoscopy. Despite the
      precautionary measures, chest wall implantations occurred rapidly at the port's
      sites in the chest wall and led to death within 24 months. We conclude that
      thoracoscopy is not a good approach for resection of anterior mediastinal masses
      in view of their possible malignant character.

PMID- 10881851
TI  - Management of retroperitoneal arterial injury after heart catheterization in
      children.
AB  - With the expansion of interventional cardiology into the pediatric population,
      vascular complications related to cardiac catheterization can be expected to
      occur. Cardiac surgeons must be prepared to treat these life-threatening
      injuries. We present a case and detail the technique of the surgical management
      of retroperitoneal arterial injury after interventional cardiac catheterization
      in a 6-month-old boy.

PMID- 10881852
TI  - Transmural necrosis of the esophagus secondary to acute aortic dissection.
AB  - A case of transmural ischemic necrosis of the esophagus secondary to aortic
      dissection is presented. A 66-year-old woman with acute type A aortic dissection
      underwent total arch replacement with a technique of deep hypothermic arrest and
      retrograde cerebral perfusion. Postoperatively she had hematemesis, and
      endoscopic examination revealed circumferential mucosal necrosis and desquamation
      of the lower esophagus. She died of multiple organ failure on postoperative day
      74. Autopsy demonstrated transmural necrosis of the esophagus secondary to
      ischemia. Ischemia of the esophagus secondary to aortic dissection is extremely
      rare.

PMID- 10881853
TI  - Surgical treatment for an unusual cause of localized bronchiectasis.
AB  - A 17-year-old girl presented with recurrent episodes of pneumonia related to
      localized bronchiectasis in the lingula. On computed tomography and magnetic
      resonance imaging, the cause of this was found to be an inwardly projecting
      exostosis arising from the left fifth rib. The patient underwent thoracotomy and
      excision of the exostosis with the affected area of lung. We report here the
      unusual case of a rib exostosis presenting with localized bronchiectasis.

PMID- 10881854
TI  - Iatrogenic main pulmonary artery-left atrial fistula in a child.
AB  - A 14-month-old boy who underwent operation for ventricular septal defect patch
      closure and debanding of the pulmonary artery presented with arterial
      desaturation in the early postoperative period. Angiography confirmed the
      echocardiographic findings of hemodynamically significant main pulmonary artery
      left atrial fistula. This communication was successfully closed surgically.

PMID- 10881855
TI  - Left ventricular outflow tract obstruction due to valve myxoma.
AB  - A life-threatening left ventricular outflow tract obstruction developed in a 26
      year-old man because of a very uncommon myxoma emerging from the ventricular side
      of the mitral valve. Immediate surgical treatment was indicated because of high
      risk factors reported herein. After transaortic resection of a single myxoma, the
      progress of this patient has been excellent, especially as a familial myxoma
      could be excluded.

PMID- 10881856
TI  - Emergency ligation of anomalous left coronary artery arising from the pulmonary
      artery.
AB  - We report two cases of successful emergency ligation of anomalous left coronary
      artery arising from the pulmonary artery (ALCAPA) in patients with previous
      cardiac arrest. Both patients had regained marginal cardiac output after
      cardiopulmonary resuscitation and had maximal doses of inotropic support. The
      ALCAPA ligation was then performed as a life-saving procedure in the absence of
      any kind of mechanical circulatory support.

PMID- 10881858
TI  - Pseudoaneurysm of the outflow graft in a patient with Novacor N100 LVAD system.
AB  - Six months after implantation of a wearable Novacor N100 left ventricular assist
      device, a 47-year-old patient developed a swelling that overlay the body of
      sternum. Computed tomographic scan of the chest revealed a pseudoaneurysm of the
      Novacor outflow graft. The patient was taken back to surgery and the diagnosis
      was confirmed at operation. Repair was performed by direct sutures via right
      anterolateral thoracotomy, under deep hypothermia and low flow technique. The
      postoperative course was uneventful.

PMID- 10881857
TI  - The stomach as a microvascularly augmented flap for esophageal replacement.
AB  - We present a case of difficult esophageal reconstruction after total
      esophagectomy for iatrogenic perforation in a diseased esophagus. The stomach was
      used for esophageal reconstruction as a retrosternal microvascularly augmented
      flap; the vascular supply to the stomach had been interrupted during previous
      abdominal operations. The blood supply to the stomach conduit was restored by
      separate arterial and venous anastomosis between the right internal thoracic
      vessels and the left gastric vessels.

PMID- 10881859
TI  - Megaesophagus from a 26-year history of achalasia.

PMID- 10881860
TI  - Aortoventriculoplasty in patients with aortic malposition.
AB  - Aortoventriculoplasty was applied successfully for recurrent combined subvalvular
      and valvular aortic obstruction that developed after intraventricular baffle
      repair of a cardiac anomaly in 2 patients with associated anterior malposition of
      the aorta. A single baffle for the left ventricular tunnel was also used for
      aortic annulus augmentation.

PMID- 10881861
TI  - A new approach to correction of tetralogy of Fallot with absent pulmonary valve.
AB  - A new technique for primary repair of tetralogy of Fallot with absent pulmonary
      valve syndrome is suggested. In addition to the standard intracardiac portion of
      tetralogy of Fallot repair, this approach includes translocation of the pulmonary
      artery anterior to the aorta, shortening of the ascending aorta, and shortening
      and plication of the pulmonary artery. This new technique should eliminate
      compression of the tracheobronchial tree caused by impingement by the pulmonary
      artery.

PMID- 10881862
TI  - High-risk bronchoscopy.
AB  - Fiberoptic bronchoscopy may be performed in patients with acute respiratory
      distress after thoracic surgical procedures as a measure to avoid intubation and
      subsequent positive-pressure ventilation in a patient with mucous impaction or as
      a method of intubating in a patient with a difficult airway. We describe the
      indications, the technique, and the potential complications.

PMID- 10881863
TI  - The innominate artery as an inflow site in coronary reoperations without
      cardiopulmonary bypass.
AB  - The innominate artery was used as an inflow site in 20 patients undergoing redo
      coronary operations without cardiopulmonary bypass. This technique was adopted
      when extensive adhesions and old patent grafts were present, to avoid dissection
      of the ascending aorta and eliminate the risk of graft injury or embolization.
      This strategy considerably facilitated construction of proximal anastomoses and
      was associated with favorable perioperative outcomes.

PMID- 10881864
TI  - Repair of esophageal perforation after treatment for achalasia.
AB  - Esophageal perforation after treatment for achalasia is a devastating
      complication. Successful closure of the perforation and relief of the obstruction
      from achalasia are paramount. This can be accomplished by careful closure of the
      mucosa. The mucosal closure is buttressed by a pedicled intercostal muscle
      carefully sewn to the edges of the muscular defect. This approach deals
      effectively with the perforation and maintains the myotomy for relief of
      esophageal obstruction from achalasia.

PMID- 10881865
TI  - Evolution of mechanical heart valves.
AB  - The need for prosthetic heart valves was long recognized but seemed an impossible
      dream before 1952 when Dr Charles Hufnagel clinically introduced a ball valve
      that he placed into the descending thoracic aorta for treatment of aortic
      valvular insufficiency. Fulfillment of that dream became a reality with the
      advent of extracorporeal circulation in the early 1950s. Development of
      prosthetic heart valves involved the search for biologically compatible materials
      and hemologically tolerant designs. Success could not be achieved without the
      union of these two factors. As there was no satisfactory mechanism to
      scientifically achieve this goal, trial and error was the method of choice. The
      development of prosthetic heart valves became the purview of the cardiovascular
      surgeon who often collaborated with engineers. To distinguish one valve from
      another each prosthesis often became identified with the surgeon developer. The
      development of bioprostheses occurred later in the development of artificial
      heart valves and constitutes a separate subject not covered in this presentation.

PMID- 10881867
TI  - Pediatric cardiac transplantation.

PMID- 10881866
TI  - Cardiac operations during pregnancy: review of factors influencing fetal outcome.
AB  - Women with underlying rheumatic heart disease, even if well compensated, can
      easily be affected by acute heart failure caused by out-of-the-ordinary
      cardiorespiratory requirements during pregnancy. In such cases, medical therapy
      is not always sufficient to drive a heart, and open heart operation might be
      necessary. Many factors associated with cardiac operations requiring
      cardiopulmonary bypass, such as hypothermia, can adversely affect both the mother
      and the fetus, but the morbidity and mortality rates are higher for the fetus
      than the mother. Because fetal heart tones were lost during cardiopulmonary
      bypass and were reheard in the intensive care unit in our case presentation, we
      have presumed that the loss of fetal heart tones should not always indicate fetal
      death and have discussed harmful factors in relation with the fetal morbidity and
      mortality in light of the literature.

PMID- 10881868
TI  - As originally published in 1994: Postoperative bronchopleural fistula: endoscopic
      closure in 12 patients. Updated in 2000.

PMID- 10881869
TI  - Chylothorax and lymphangiomyomatosis.

PMID- 10881870
TI  - Moderate mitral insufficiency in coronary disease: when should it be corrected?

PMID- 10881871
TI  - Ruptured bronchial artery aneurysm.

PMID- 10881872
TI  - Interventional closure of a fenestrated Fontan avoids cytokine production.

PMID- 10881873
TI  - Only redox state of cytochrome a,a3 reflects adequacy of tissue oxygenation.

PMID- 10881874
TI  - Harmonic scalpel: a word of caution.

PMID- 10881875
TI  - Catamenial pneumothorax: a unifying concept.

PMID- 10881876
TI  - Cardiovascular effects of inhaled nitric oxide in a canine model of
      cardiomyopathy.

PMID- 10881877
TI  - Aortocoronary graft markers and subsequent catheterization.

PMID- 10881878
TI  - Left atrial reduction for chronic atrial fibrillation.

PMID- 10881879
TI  - Predictive factors for persistence of atrial fibrillation after mitral valve
      operation.

PMID- 10881880
TI  - Analysis of stage I lung carcinoma patients including p53 and Rb protein.

PMID- 10881881
TI  - Partial clamping of the inferior vena cava.

PMID- 10881882
TI  - Left internal mammary artery branches after minimally invasive harvesting.

PMID- 10881883
TI  - Safeguarding participants in clinical trials.

PMID- 10881884
TI  - Symptomless infection with Ebola virus.

PMID- 10881885
TI  - Quantitative tests for human papillomavirus.

PMID- 10881886
TI  - Strategies for coronary stenting.

PMID- 10881888
TI  - Short cut to continence?

PMID- 10881887
TI  - Insulin resistance, iron, and the liver.

PMID- 10881889
TI  - Pendulum test in cerebral palsy.

PMID- 10881890
TI  - Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture
      among older women.
AB  - BACKGROUND: Inhibitors of hydroxymethylglutaryl-coenzyme A reductase (statins)
      increase new bone formation in rodents and in human cells in vitro. Statin use is
      associated with increased bone mineral density of the femoral neck. We undertook
      a population-based case-control study at six health-maintenance organisations in
      the USA to investigate further the relation between statin use and fracture risk
      among older women. METHODS: We investigated women aged 60 years or older.
      Exposure, outcome, and confounder information was obtained from automated claims
      and pharmacy data from October, 1994, to September, 1997. Cases had an incident
      diagnosis of non-pathological fracture of the hip, humerus, distal tibia, wrist,
      or vertebrae between October, 1996, and September, 1997. Controls had no fracture
      during this period. We excluded women with records of dispensing of drugs to
      treat osteoporosis. FINDINGS: There were 928 cases and 2747 controls. Compared
      with women who had no record of statin dispensing during the previous 2 years,
      women with 13 or more statin dispensings during this period had a decreased risk
      of non-pathological fracture (odds ratio 0.48 [95% CI 0.27-0.83]) after
      adjustment for age, number of hospital admissions during the previous year,
      chronic disease score, and use of non-statin lipid-lowering drugs. No association
      was found between fracture risk and fewer than 13 dispensings of statins or
      between fracture risk and use of non-statin lipid-lowering drugs. INTERPRETATION:
      Statins seem to be protective against non-pathological fracture among older
      women. These findings are compatible with the hypothesis that statins increase
      bone mineral density in human beings and thereby decrease the risk of
      osteoporotic fractures.

PMID- 10881891
TI  - Viral load of human papilloma virus 16 as a determinant for development of
      cervical carcinoma in situ: a nested case-control study.
AB  - BACKGROUND: Infection with certain types of human papillomavirus (HPV), which is
      common among young women, increases the risk of cervical cancer. However, less
      than 1% of young women positive for oncogenic types of HPV develop cervical
      cancer. We investigated whether the amount of HPV DNA is a useful predictor of
      progression to cervical carcinoma in situ. METHODS: We estimated the amount of
      HPV 16 DNA by a PCR that uses the 5'-exonuclease (Taqman) method, in 478 women
      with cervical carcinoma in situ and 608 individually matched controls. To adjust
      for differences in the amount of genomic DNA between samples, we estimated the
      amount of a nuclear gene (beta-actin). We studied multiple smears (total 3835
      archived samples) from each woman, taken over periods of up to 26 years, that
      covered normal cytology to development of cervical cancer. FINDINGS: The risk of
      cervical carcinoma in situ increased with the amount of HPV 16 DNA. Analysis of
      the first smear from each woman, collected a mean of 7.8 years before cancer
      diagnosis, showed that women with the 20% highest amount of HPV 16 DNA were at a
      60-fold higher risk of developing cervical carcinoma in situ than women negative
      for HPV 16. The first smear samples were classified as normal by squamous-cell
      cytology. INTERPRETATION: Analysis of the amount of HPV DNA can predict cancer
      risk at a stage when current screening methods are uninformative. Testing for the
      amount of HPV 16 DNA during gynaecological health checks might strikingly improve
      our ability to distinguish between infections that have a high or low risk of
      progressing into cervical cancer.

PMID- 10881892
TI  - Consistent high viral load of human papillomavirus 16 and risk of cervical
      carcinoma in situ: a nested case-control study.
AB  - BACKGROUND: Persistent infection with certain types of human papillomavirus (HPV)
      is believed to be a prerequisite for the development of cervical neoplasia.
      Persistence may depend on certain characteristics, such as viral load, which has
      so far been given little attention. We investigated the association between HPV
      16 viral load and cervical carcinoma in situ. METHODS: We did a nested case
      control study of women participating in cytological screening in Sweden. We used
      a sensitive quantitative PCR assay to estimate HPV 16 load in multiple smears for
      each woman, taken during a period of up to 26 years before diagnosis. We
      calculated C, values, which decrease as the number of viral DNA copies increases.
      FINDINGS: 2081 smears from 478 cases and 1754 smears from 608 controls were
      tested. Among cases, we found a consistently increased load of HPV 16 already 13
      years or more before diagnosis, and when many smears were still cytologically
      normal. Women with high HPV 16 viral loads were at least 30 times the relative
      risk of HPV-16-negative women more than a decade before diagnosis. The increase
      in relative risk was constant over time. About 25% of women (95% CI 0.12-0.32)
      infected with a high viral load before age 25 years developed cervical carcinoma
      in situ within 15 years. INTERPRETATION: Cervical carcinoma in situ associated
      with HPV 16 occurs mainly in HPV-16-positive women who have consistently high
      viral loads long term. Women at high risk could be identified by use of a
      quantitative HPV test in addition to cytological screening.

PMID- 10881893
TI  - Optimum percutaneous transluminal coronary angioplasty compared with routine
      stent strategy trial (OPUS-1): a randomised trial.
AB  - BACKGROUND: Whether routine implantation of coronary stents is the best strategy
      to treat flow-limiting coronary stenoses is unclear. An alternative approach is
      to do balloon angioplasty and provisionally use stents only to treat suboptimum
      results. We did a multicentre trial to compare the outcomes of patients treated
      with these strategies. METHODS: We randomly assigned 479 patients undergoing
      single-vessel coronary angioplasty routine stent implantation or initial balloon
      angioplasty and provisional stenting. We followed up patients for 6 months to
      determine the composite rate of death, myocardial infarction, cardiac surgery,
      and target-vessel revascularisation. RESULTS: Stents were implanted in 227
      (98.7%) of the patients assigned routine stenting. 93 (37%) patients assigned
      balloon angioplasty had at least one stent placed because of suboptimum
      angioplasty results. At 6 months the composite endpoint was significantly lower
      in the routine stent strategy (14 events, 6.1%) than with the strategy of balloon
      angioplasty with provisional stenting (37 events, 14.9%, p=0.003). The cost of
      the initial revascularisation procedure was higher than when a routine stent
      strategy was used (US$389 vs $339, p<0.001) but at 6 months, average per-patient
      hospital costs did not differ ($10,206 vs $10,490). Bootstrap replication of 6
      month cost data showed continued economic benefit of the routine stent strategy.
      INTERPRETATION: Routine stent implantation leads to better acute and long-term
      clinical outcomes at a cost similar to that of initial balloon angioplasty with
      provisional stenting.

PMID- 10881894
TI  - War and mortality in Kosovo, 1998-99: an epidemiological testimony.
AB  - BACKGROUND: The total number, rates, and causes of mortality in Kosovo during the
      last war remain unclear despite intense international attention. Understanding
      mortality that results from modern warfare, in which 90% of casualties are
      civilian, and identifying vulnerable civilian groups, are of critical public
      health importance. METHODS: In September 1999 we conducted a two-stage cluster
      survey among the Kosovar Albanian population in Kosovo. We collected
      retrospective mortality data, including cause of death, for the period of the
      conflict. FINDINGS: The survey included 1197 households comprising 8605 people.
      From February, 1998, through June, 1999, 67 (64%) of 105 deaths in the sample
      population were attributed to war-related trauma, corresponding to 12,000 (95% CI
      5500-18,300) deaths in the total population. The crude mortality rate increased
      2.3 times from the pre-conflict level to 0.72 per 1000 a month. Mortality rates
      peaked in April 1999 at 3.25 per 1000 a month, coinciding with an intensification
      of the Serbian campaign of "ethnic cleansing". Men of military age (15-49 years)
      and men 50 years and older had the highest age-specific mortality rates from war
      related trauma. However, the latter group were more than three times as likely to
      die of war-related trauma than were men of military age (relative risk 3.2).
      INTERPRETATION: Raising awareness among the international humanitarian community
      of the increased risk of mortality from war-related trauma among men of 50 years
      and older in some settings is an urgent priority. Establishing evacuation
      programmes to assist older people to find refuge may prevent loss of life. Such
      mortality data could be used as evidence that governments and military groups
      have violated international standards of conduct during warfare.

PMID- 10881896
TI  - A girl who laughed and fell down.

PMID- 10881895
TI  - Human asymptomatic Ebola infection and strong inflammatory response.
AB  - BACKGROUND: Ebola virus is one of the most virulent pathogens, killing a very
      high proportion of patients within 5-7 days. Two outbreaks of fulminating
      haemorrhagic fever occurred in northern Gabon in 1996, with a 70% case-fatality
      rate. During both outbreaks we identified some individuals in direct contact with
      sick patients who never developed symptoms. We aimed to determine whether these
      individuals were indeed infected with Ebola virus, and how they maintained
      asymptomatic status. METHODS: Blood was collected from 24 close contacts of
      symptomatic patients. These asymptomatic individuals were sampled 2, 3, or 4
      times during a 1-month period after the first exposure to symptomatic patients.
      Serum samples were analysed for the presence of Ebola antigens, virus-specific
      IgM and IgG (by ELISA and western blot), and different cytokines and chemokines.
      RNA was extracted from peripheral blood mononuclear cells, and reverse
      transcriptase-PCR assays were done to amplify RNA of Ebola virus. PCR products
      were then sequenced. FINDINGS: 11 of 24 asymptomatic individuals developed both
      IgM and IgG responses to Ebola antigens, indicating viral infection. Western-blot
      analysis showed that IgG responses were directed to nucleoprotein and viral
      protein of 40 kDa. The glycoprotein and viral protein of 24 kDa genes showed no
      nucleotide differences between symptomatic and asymptomatic individuals.
      Asymptomatic individuals had a strong inflammatory response characterised by high
      circulating concentrations of cytokines and chemokines. INTERPRETATION: This
      study showed that asymptomatic, replicative Ebola infection can and does occur in
      human beings. The lack of genetic differences between symptomatic and
      asymptomatic individuals suggest that asymptomatic Ebola infection did not result
      from viral mutations. Elucidation of the factors related to the genesis of the
      strong inflammatory response occurring early during the infectious process in
      these asymptomatic individuals could increase our understanding of the disease.

PMID- 10881897
TI  - Stopping primary prophylaxis in HIV-1-infected patients at high risk of
      toxoplasma encephalitis. Swiss HIV Cohort Study.
AB  - Discontinuation of primary prophylaxis against toxoplasma encephalitis was
      studied in 199 HIV-1-infected patients on antiretroviral combination treatment
      who had experienced a sustained increase in their CD4 count. During a follow-up
      of 272 person-years, no cases of toxoplasma encephalitis arose.

PMID- 10881898
TI  - Oral statins and increased bone-mineral density in postmenopausal women.
AB  - Experimental evidence suggests that the cholesterol-lowering drugs statins
      increase bone formation. We report a significant increase of bone-mineral density
      associated with taking statins in postmenopausal women.

PMID- 10881899
TI  - Reassessing artificial bowel sphincters.
AB  - The artificial sphincter has now been used for the treatment of patients with
      faecal incontinence since 1996. Presently, results in the UK do not match those
      reported from the rest of Europe, with infection caused by methicillin-resistant
      Staphylococcus aureus being the most common cause of failure.

PMID- 10881900
TI  - Treatment of DYT1-generalised dystonia by stimulation of the internal globus
      pallidus.
AB  - In seven selected patients with dystonia musculorum deformans-1 generalised
      dystonia (DYT1), continuous bilateral stimulation of the globus pallidus internus
      was associated with substantial improvement of dystonia and functional
      disability.

PMID- 10881901
TI  - Stability and sterility of recombinant tissue plasminogen activator at -30
      degrees C.
AB  - We assessed whether frozen recombinant tissue plasminogen activator (rt-PA)
      remains stable and sterile for up to 22 weeks at -30 degrees C. Our findings
      confirm that rt-PA is a cost-effective alternative to urokinase for restoring
      patency to occluded central venous catheters.

PMID- 10881902
TI  - Relation between cholinesterase inhibitor and Pisa syndrome.
AB  - We report two patients who developed Pisa syndrome after treatment with
      cholinesterase inhibitors--cognition-enhancing novel agents for patients with
      Alzheimer's disease. Cholinergic excess could be another factor in Pisa syndrome,
      especially in cholinergically-imbalanced Alzheimer's disease.

PMID- 10881903
TI  - WHO compares health-care systems across the globe.

PMID- 10881904
TI  - Telomerase: are we expecting too much?

PMID- 10881905
TI  - Japanese health goals go up in smoke.

PMID- 10881906
TI  - Canada reacts to water contamination.

PMID- 10881907
TI  - North and South: bridging the information gap.
AB  - Information exchange is critical for development of health systems. The
      information needs of less-developed countries are especially challenging, but
      many factors inhibit free flow of knowledge. There is much talk about how
      technical fixes--such as the internet--might fill this information gap. Yet few
      attempts have been made to ask clinical investigators who work in resource-poor
      regions for their views on these difficulties and the possible solutions. The
      messages reported here, from a survey of Lancet editorial advisors, suggest that
      information, research, and publication capacities are intimately linked.
      Investigators, publishers, editors, and editorial organisations all have
      important parts to play in solving this global information poverty.

PMID- 10881908
TI  - Advances and research directions in the prevention of mother-to-child HIV-1
      transmission.
AB  - Although substantial progress has been made in preventing mother-to-child HIV-1
      transmission in the past decade, critical research questions remain. Two
      perinatal epidemics now exist. In more-developed countries, integration of
      prenatal HIV-1 counselling and testing programmes into an existing antenatal
      infrastructure, availability of effective antiretroviral prophylaxis, and access
      to infant formula have resulted in new perinatal infections becoming rare.
      However, identification of missed prevention opportunities, the causes of
      prophylaxis failure, and the potential effects of in-utero antiretroviral
      exposure have become a priority. In less-developed countries, antenatal care is
      limited, testing programmes are almost non-existent, effective interventions
      remain unimplemented, and prevention of postnatal transmission through breastmilk
      while maintaining adequate infant nutrition is a major dilemma. The challenge for
      the next decade is to simultaneously address questions relevant to both epidemics
      while bridging the gap in prevention of perinatal transmission between more
      developed and less-developed countries.

PMID- 10881909
TI  - Antimalarial drug combination policy: a caveat.

PMID- 10881910
TI  - Access to medical information in developing countries.

PMID- 10881911
TI  - Homocysteine and heart disease in Indian Asians.

PMID- 10881912
TI  - Homocysteine and heart disease in Indian Asians.

PMID- 10881913
TI  - Homocysteine and heart disease in Indian Asians.

PMID- 10881915
TI  - Migraine revolution and sumatriptan.

PMID- 10881914
TI  - Homocysteine and heart disease in Indian Asians.

PMID- 10881916
TI  - Early laparoscopy for abdominal pain.

PMID- 10881917
TI  - Meningococcal immunisation in Ghana.

PMID- 10881918
TI  - Meningococcal immunisation in Ghana.

PMID- 10881919
TI  - Haemorrhoidectomy: painful choice.

PMID- 10881920
TI  - Haemorrhoidectomy: painful choice.

PMID- 10881921
TI  - Atopy and sudden cardiac death.

PMID- 10881922
TI  - Neuraminidase inhibitor and amantadine.

PMID- 10881923
TI  - Medicine in Austria.

PMID- 10881924
TI  - Financing vaccines.

PMID- 10881925
TI  - Diagnosis of tuberculosis in Africa.

PMID- 10881926
TI  - Satisfying birthing experiences in Japan.

PMID- 10881927
TI  - The Nobel chronicles. 1994: Alfred G Gilman (b 1941) and Martin Rodbell (1925
      98).

PMID- 10881928
TI  - A new biodegradable stent for the pancreaticojejunal anastomosis after
      pancreaticoduodenal resection: in vitro examination and pilot experiences in
      humans.
AB  - We sought to develop a biodegradable pancreatic stent that could be easily placed
      at operation into the human pancreatic duct and the degradation of which could be
      easily followed up. Spiral-shaped, gamma-sterilized stents were manufactured of
      0.4-mm polylactide wire in which there was added 23 weight-% barium sulfate. The
      biodegradability of the stents was studied in vitro at two different pH values,
      the first resembling that of pancreatic juice and the other that of bile. The
      effects of enzymoactivity in the test solution and the composition of the stents
      (with or without barium addition) also were tested. These kinds of stents have
      been experimented with in two pilot patients. Degradation of the stents occurred
      from 24 to 52 weeks of incubation. Alkaline milieu together with the presence of
      pancreatic enzyme made the stents degrade twice as fast as when either alkaline
      milieu or enzyme was present. In the milieu resembling pancreatic juice, barium
      sulfate had no effect on the degradation time. Neither of the pilot patients had
      any postoperative complications. Biodegradable, x-ray-positive stents degrade
      faster in pancreatic than in biliary milieu. Their safety and efficacy in human
      pancreaticojejunal anastomoses need further study.

PMID- 10881929
TI  - Chemokines MCP-1 and RANTES in isolated rat pancreatic acinar cells treated with
      CCK and ethanol in vitro.
AB  - The role of cholecystokinin (CCK) and ethanol on the expression and secretion of
      monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T
      cell expressed and secreted (RANTES) chemokines from isolated rat pancreatic
      acinar cells was investigated. CCK at concentrations of 1 nM and 100 nM and
      ethanol at concentrations of 75, 200, 400, and 600 mM were used to stimulate
      isolated acini. The levels of MCP-1 and RANTES in the incubation medium were
      determined by enzyme-linked immunoabsorbent assay (ELISA). In the control groups,
      MCP-1 and RANTES were secreted into the incubation medium, and both increased
      with time. MCP-1 increased from baseline 17.6 pg/ml to 74.1 pg/ml, whereas RANTES
      increased from 255.5 to 318.3 pg/ml at 390 min. CCK at 100 nM caused a sustained
      increase in MCP-1 levels to 89.6 pg/ml at 390 min in the incubation medium,
      whereas the levels of RANTES gradually decreased after 180 min and reached its
      lowest level at 390 min. Ethanol at a concentration of 600 mM increased the
      levels of RANTES in the incubation medium, but inhibited the levels of MCP-1 at
      all concentrations (75, 200, 400, and 600 mM). In summary, rat pancreatic acinar
      cells secrete MCP-1 and RANTES, and the stimulation of these chemokines by CCK
      and ethanol suggests that they may be involved in the pathogenesis of acute
      pancreatitis.

PMID- 10881930
TI  - The expression of chemokine genes correlates with nuclear factor-kappaB
      activation in human pancreatic cancer cell lines.
AB  - Chemokines may regulate the process of immune cell infiltration that is often
      found in pancreatic cancer. In this study, we investigated the secretion of the
      chemokines [interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, and
      RANTES (regulated on activation, normal T cell expressed and secreted)] in human
      pancreatic cancer cell lines. The chemokine secretion in three pancreatic cancer
      cell lines (PANC-1, MIA PaCa-2, and BxPC-3) was evaluated by enzyme-linked
      immunosorbent assay (ELISA) and Northern blot, and the activation of nuclear
      factor-kappaB (NF-kappaB) and NF-IL6 was assessed by an electrophoretic gel
      mobility shift assay (EMSA). Without any stimulation, IL-8 secretion was detected
      in all cell lines, and MCP-1 secretion was detected in PANC-1 and MIA PaCa-2
      cells. However, RANTES secretion was not detected in all cells. The addition of
      IL-1beta and tumor necrosis factor (TNF)-alpha strongly enhanced IL-8, MCP-1, and
      RANTES secretion; these responses were observed at the mRNA level as well as at
      the protein level. IL-1beta and TNF-alpha induced a rapid activation of nuclear
      factor (NF)-kappaB in PANC-1 cells, and the increase in chemokine mRNA expression
      correlated with NF-kappaB activation. The activation of NF-IL6 was modest. A
      blockade of NF-kappaB activation by TPCK markedly reduced the IL-1beta- and TNF
      alpha-induced chemokine gene expression. Our findings indicate that chemokines
      are produced by pancreatic cancer cells, and suggest that these factors may
      contribute to the accumulation of tumor-associated immune cells. In addition, the
      transcriptional activation of chemokine genes in pancreatic cancer cells may be
      closely associated with NF-kappaB activation.

PMID- 10881931
TI  - Trypsin stimulates production of cytokines from peritoneal macrophages in vitro
      and in vivo.
AB  - Acute pancreatitis (AP) is characterized by release of proteolytic enzymes from
      the pancreas and a powerful inflammatory cytokine cascade that mediates the
      systemic manifestations and contributes to the mortality of the disease. The
      purpose of this study was to examine a potential link between pancreatic
      proteolytic enzymes, which are increased in AP, and cytokine production. To
      evaluate this, we incubated rat peritoneal macrophages (PMO) with increasing
      concentrations of trypsin and measured cytokine production. Supernatants from the
      cell cultures were assayed for TNF-alpha and IL-1beta, and the PMO were collected
      for the evaluation of cytokine mRNA by polymerase chain reaction (PCR). Further
      to evaluate the role of pancreatic proteases in triggering the cytokine cascade
      in AP, trypsin was injected into the peritoneal cavity of Sprague-Dawley rats,
      and the production of cytokines was measured in the peritoneal fluid. Controls
      included injection of inactivated trypsin. Incubation of PMO with trypsin in
      vitro resulted in a dose-dependent increase in TNF-alpha production with maximal
      response (2,660.5+/-748.8 pg/mL) at 10 microg/mL protease. Peak TNF-alpha and IL
      1beta release was noted 16 h after stimulation of the PMO (2,759.5+/-698.0 pg/mL
      and 160,596+/-4,065 cpm, respectively). Trypsin-induced TNF-alpha production was
      not due to release of cell-associated cytokine, inasmuch as activation of PMO
      with this protease causing an increase in TNF-alpha mRNA by 30 minutes, reaching
      a 14-fold increase at 4 h. Trypsin-injected animals produced TNF-alpha-containing
      ascitic fluid in a dose-dependent manner with peak TNF-alpha at 2 h (371.3+/-180
      pg/mL) versus control (53.8+/-11.2 pg/mL; p < 0.022). No TNF-alpha was found in
      ascites of rats injected with heat-inactivated trypsin. Histologic examination of
      trypsin-injected animals revealed evidence of pulmonary inflammation at 2 and 4
      hours. We conclude that the proteolytic enzyme trypsin stimulates cytokine
      production from macrophages in vitro and in vivo. This model demonstrates for the
      first time that trypsin is a potential mediator of the cytokine response seen
      during AP.

PMID- 10881933
TI  - Genes, cloned cDNAs, and proteins of human trypsinogens and pancreatitis
      associated cationic trypsinogen mutations.
AB  - Historically, trypsinogens/trypsins have been one of the most extensively studied
      enzyme models of protein structure and function. They have received renewed
      attention after the identification of mutations in the cationic trypsinogen gene
      as being associated with hereditary pancreatitis. A survey of the literature
      revealed five cloned cDNAs, but only three protein products of human
      trypsinogens, and their nomenclature has been confusing. The availability of the
      complete genomic sequencing of the human trypsinogen gene family made it possible
      to provide a systematic review of the genes, cDNAs, and protein products of human
      trypsinogens and to clarify some controversial issues. Further, the confusing
      coexistence of two systems for naming the cationic trypsinogen mutations is
      addressed.

PMID- 10881932
TI  - Autocrine growth effect of IL-8 and GROalpha on a human pancreatic cancer cell
      line, Capan-1.
AB  - A human pancreatic cancer cell line, Capan-1, secretes the chemokines interleukin
      8 (IL-8) and growth-related oncogene alpha (GROalpha). Capan-1 cells also express
      the chemokine receptor 2 (CXCR2), which is a Gialpha-protein coupled receptor.
      Growth of Capan-1 cells was inhibited when anti-IL-8 or anti-GROalpha monoclonal
      antibody was added into the culture medium. Pertussis toxin, which blocks Gialpha
      also demonstrated a growth-inhibitory effect on Capan-1 cells. These results
      indicated that IL-8 and GROalpha act on Capan-1 cells as growth factors in an
      autocrine manner through CXCR2.

PMID- 10881934
TI  - Neogenesis of pancreatic endocrine cells in copper-deprived rat models.
AB  - Transplantation of progenitor cells for regeneration of islet cells could prove
      invaluable in the treatment of diabetes mellitus. This study provides evidence
      that in rats maintained on a copper-deficient diet containing the copper
      chelating agent tetraethylenepentamine pentahydrochloride, regeneration of single
      alpha and beta endocrine cells in the ductules and acinar tissue of the adult rat
      pancreata occurred. These regenerated cells both in the ductules and acinar
      tissue stained positive for glucagon and insulin similar to cells within the
      islets and in addition to being reactive to proliferative cellular nuclear
      antigen, an intracellular marker of active proliferation. In contrast, the
      control group pancreata did not show any evidence of islet regeneration,
      proliferation, or proliferative cellular nuclear antigen reactivity pre- or
      posttransplantation. Transplantation of digested pancreatic tissues from the
      copper-deficient group into the spleen of syngeneic diabetic rats reversed
      diabetes, and this was confirmed histologically by demonstrating cells within
      ductules that stained positively for insulin. This study concludes that copper
      deprivation contributes to the neogenesis of pancreatic alpha and beta cells in
      the ductules and acinar tissue of adult pancreas in rat model and that
      transplanted stem cells maintain their functional capacity in the recipient after
      transplantation.

PMID- 10881935
TI  - Magnetic resonance imaging to measure therapeutic response using an orthotopic
      model of human pancreatic cancer.
AB  - Pancreatic cancer is one of the most incurable and lethal human cancers in the
      United States. To facilitate development of novel therapeutic agents, we
      previously established an orthotopic pancreatic tumor model that closely mimics
      the natural biological behavior of human pancreatic cancer. In this study,
      magnetic resonance imaging (MRI) techniques were developed to detect tumor
      formation noninvasively and monitor serially tumor growth kinetics in this
      orthotopic model used for experimental drug testing. By using an optimized T2
      weighted imaging method, we were able to distinguish human pancreas cancer from
      normal mouse pancreas. Orthotopic tumor formation was detected as early as day 1
      after tumor cell implantation with a tumor volume as small as 12 mm3. Mice with
      evidence of tumor were separated into four treatment groups: control, auristatin
      PE, gemcitabine, and their combination. After treatment, the mice were imaged at
      least three times before termination of the experiment. Comparison between MRI
      tumor volume measurements and tumor weights made at biopsy resulted in a
      correlation coefficient of 0.98. The tumor growth curves constructed from serial
      magnetic resonance imaging (MRI) measurements clearly showed tumor growth
      inhibition in treated mice compared with the control group. As expected, the
      group treated with the combination had the highest response rate compared with
      either auristatin-PE or gemcitabine alone, and the data were statistically highly
      significant (p < 0.004). From these results, we conclude that noninvasive MRI can
      be used to monitor serially therapeutic response in this orthotopic human
      pancreatic tumor model and can be used in the future to evaluate novel antitumor
      agents before human studies.

PMID- 10881936
TI  - Different amounts of K-ras mutant epithelial cells in pancreatic carcinoma and
      mass-forming pancreatitis.
AB  - Clinically, differential diagnosis of pancreatic carcinoma (PC) and so-called
      "mass-forming pancreatitis (MFP)" is difficult. We analyzed the amount, ductal
      level, and K-ras mutation of ductal hyperplasia and intraductal carcinoma in
      surgically resected cases of MFP (n = 18) and PC (n = 16). DNAs extracted from
      microdissected epithelial foci were analyzed for K-ras codon 12 mutation by
      nested polymerase chain reaction and restriction fragment length polymorphism.
      The histology of MFP showed severe destruction of exocrine tissue and pancreatic
      stones and/or protein plugs (72%, 13 of 18 cases) in mostly peripheral ducts. The
      average basal membrane lengths of nonpapillary and papillary hyperplasia in cases
      of carcinoma were about 4 and 15 times more than those of MFP, respectively. The
      frequency of K-ras mutation in hyperplastic foci increased from nonpapillary [six
      (27%) of 22] to papillary foci [16 (64%) of 25] in K-ras mutant PCs, but there
      was no difference between nonpapillary [one (6%) of 18] and papillary foci (none
      of 19) in K-ras wild-type PCs, and also between nonpapillary (none of 24) and
      papillary foci [one (7%) of 14] in MFPs.

PMID- 10881937
TI  - Induction of acute pancreatitis by cerulein in human IL-6 gene transgenic mice.
AB  - Whether acute pancreatitis induced by cerulein was aggravated in human
      interleukin 6 (IL-6) transgenic mice and whether a specific anti-IL-6 receptor
      antibody improved pancreatitis were investigated. To induce acute pancreatitis,
      cerulein (50 microg/kg, seven injections) with or without 1 mg/kg
      lipopolysaccharides (LPS) was injected intraperitoneally every hour. In some
      mice, a monoclonal anti-IL-6 receptor antibody was administered before the first
      cerulein injection. The animals were killed 1 hour after the last injection. The
      pancreatic wet weight induced by cerulein alone was significantly higher in IL-6
      transgenic mice compared with wild-type mice, but pretreatment with a specific
      anti-IL-6 receptor antibody did not reduce interstitial edema. When cerulein was
      administered with LPS, the pancreatic wet weight increased much more than when
      pancreatitis was induced by cerulein alone in both genotypes, and pretreatment
      with the anti-IL-6 receptor antibody decreased the pancreatic edema only in human
      IL-6 transgenic mice. These results suggest that anticytokine antibodies may be
      effective in improving acute pancreatitis.

PMID- 10881938
TI  - Basement membrane exposure defines a critical window of competence for pancreatic
      duct differentiation from undifferentiated pancreatic precursor cells.
AB  - We previously showed that the undifferentiated pancreatic epithelium can
      differentiate into islets, ducts, or acini depending on its milieu and that
      laminin is necessary for pancreatic duct formation. Therefore we wanted to study
      the plasticity of laminin-induced duct differentiation the better to understand
      mechanisms of pancreatic duct lineage selection induced by basement membrane.
      Mouse embryonic pancreases were dissected at gestational day 11 (E11.5), and
      epithelium was isolated from its surrounding mesenchyme. Some epithelia were
      cultured in a collagen gel devoid of laminin. These epithelia were "rescued" at
      days 1-7 of culture by transferring them to a laminin-rich matrix (Matrigel) for
      7 additional days. Other epithelia were instead first cultured in Matrigel, and
      then placed into collagen. Immunohistochemistry was performed for insulin,
      amylase, and carbonic anhydrase II. Pancreatic epithelia rescued from collagen
      into laminin during days 1-4 after harvest were still able to form ducts, whereas
      epithelia deprived of laminin for longer than this 4-day window were not.
      Pancreatic epithelia exposed to laminin for as little as 1 day, and then placed
      into collagen, still retained the ability to make ducts. Thus there is a clear
      cut-off in the development of the pancreatic epithelium at E11.5, after which
      laminin appears necessary to induce duct formation. We believe that such "windows
      of competence" in embryonic development imply that developmental programs in the
      embryo allow some flexibility.

PMID- 10881939
TI  - Severe chronic hypoglycemia in a lean, young woman.

PMID- 10881940
TI  - Surgical resection of isolated pancreatic tuberculosis presenting as obstructive
      jaundice.

PMID- 10881942
TI  - A case of primary hydatid disease of the pancreas simulating cystic neoplasm.

PMID- 10881941
TI  - A small serous cystadenoma of the pancreas: endoscopic ultrasonographic findings.

PMID- 10881943
TI  - Cytoplasmic vacuole generation in rat isolated pancreatic acini under
      secretagogue hyperstimulation is associated with intracellular acidification.

PMID- 10881944
TI  - Constipation after hysterectomy: fact or fiction?
AB  - Hysterectomy is responsible for numerous postoperative complications largely
      urological, but sometimes of sexual or colorectal function. The latter involve
      modifications of bowel function resulting in constipation as a result of delayed
      transit, infrequent evacuations and greater difficulty in expelling faeces. We
      have reviewed the topic, and consider the various hypotheses whereby these
      modifications may result from hormonal alterations, iatrogenic causes, or
      variations in recto-bladder sensitivity. Any of these could justify the
      modifications in bowel function detected in these patients. The studies carried
      out so far provide no clear information about the type of constipation that
      develops after hysterectomy, as we lack prospective studies that compare bowel
      function before and after operations. Nor is it clear whether we are dealing with
      constipation as a result of delayed transit or obstructed defaecation, nor which
      pathogenetic mechanisms are involved. In view of the large number of
      hysterectomies that are done, sometimes prophylactically, controlled prospective
      studies are warranted to address these issues more fully.

PMID- 10881945
TI  - Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned
      medium is facilitated by granulocyte-macrophage colony-stimulating factor.
AB  - OBJECTIVE: To investigate the effect of different cytokines that are present in
      tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell
      transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland.
      MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB
      231. INTERVENTIONS: Human PMN treated with either tumour-conditioned medium or
      different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231
      cells were plated on macrovascular and microvascular endothelial monolayers in
      collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME
      MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function
      and receptor expression, and tumour cell transmigration. RESULTS: tumour
      conditioned medium contained high concentrations of granulocyte-macrophage colony
      stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and
      interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and
      interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced
      transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05),
      whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In
      addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN
      CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05).
      CONCLUSION: These results indicate that the GM-CSF that is present in tumour
      conditioned medium may be involved, at least in part, in alterations in PMN
      function mediated by the medium and subsequently PMN-induced transmigration of
      tumour cells.

PMID- 10881946
TI  - Bacterial translocation in obstructive jaundice in rats: role of mucosal
      lacteals.
AB  - OBJECTIVE: To study the ultrastructure of the ileal wall in rats with obstructive
      jaundice alone and after passive external biliary drainage to see if we could
      discover the reason for the increased risk of infective complications and
      multisystem failure in the presence of obstructive jaundice and after external
      biliary drainage. DESIGN: Histological examination of the wall of the terminal
      ileum using light microscopy, as well as scanning and transmission electron
      microscopy (EM). SETTING: Experimental laboratory, Republic of Georgia. ANIMALS:
      56 adult male Wistar rats. INTERVENTIONS: Rats were divided into 7 groups:
      controls (not operated on, n = 6); sham-operated and studied after 6 and 12 days
      (n = 6 in each); bile duct ligation alone studied after 6 and 12 days (n = 10 in
      each); and bile duct ligation followed 6 and 12 days later by one-day of external
      biliary drainage (n = 9 in each). MAIN OUTCOME MEASURES: Percentage of destroyed
      villi. RESULTS: The extent of oedema of villi, necrosis of neurons, and
      disturbances in the secretory capacity of enterocytes correlated well with the
      duration of cholestasis. After 6 and 12 days ligation alone 7.2% and 17.3%,
      respectively, of villi were found to be destroyed; their connective tissue
      framework including lymphatics was in direct contact with the intestinal
      contents. The changes were not reversed by one day of external biliary drainage.
      CONCLUSION: The gaps in the ileal mucosa caused by obstructive jaundice (and not
      relieved by one day of external biliary drainage) may enable gut bacteria and
      their endotoxin to reach the systemic circulation through the lymphatic-system.
      This could increase the risk of infective complications.

PMID- 10881947
TI  - Taurine protects against early and late skeletal muscle dysfunction secondary to
      ischaemia reperfusion injury.
AB  - OBJECTIVE: To assess the efficacy of the cytoprotective B-amino acid taurine in
      prevention of skeletal muscle dysfunction secondary to ischaemia-reperfusion (IR)
      injury. DESIGN: Randomised controlled animal study. SETTING: Biomedical research
      laboratory, teaching hospital, Republic of Ireland. ANIMALS: 96 Sprague Dawley
      rats. INTERVENTIONS: Rats were randomised into three groups (n = 24/group):
      control (sham); ischaemia-reperfusion (untreated); and ischaemia-reperfusion +
      taurine. A further 24 rats were given taurine alone. The rat cremaster skeletal
      muscle model of four hours of ischaemia followed by reperfusion was used. Taurine
      4%wt/vol was given in the animals' water throughout the experiment, beginning 48
      hours before the ischaemia was initiated. OUTCOME MEASURES: 8 rats were killed
      from each group and muscle contractile function was assessed using electrical
      field stimulation in a tissue bath at 24 hrs, 48 hrs and 7 days. RESULTS:
      Ischaemia followed by 24 hours, 48 hours or 7 days of reperfusion resulted in
      significant reduction in both muscle twitch and tetanic contractile function (p <
      0.05). This was reversed by taurine, which resulted in significant preservation
      of twitch and tetanic contractility at all time points including one week of
      reperfusion (p < 0.05). There was no difference in muscle function between muscle
      treated with taurine after ischaemia-reperfusion and control muscle, with the
      same operation but without ischaemia, from 48 hours onwards. CONCLUSIONS: These
      data show that pharmaceutical use of the endogenous amino acid taurine, unlike
      many-other agents, protects electrophysiological function in skeletal muscle
      against both early and late ischaemia-reperfusion injury.

PMID- 10881948
TI  - Chemical lumbar sympathectomy revisited: survey of the current practice of
      vascular surgeons in Scotland.
AB  - OBJECTIVE: To investigate the current practice of chemical lumbar sympathectomy
      by vascular surgeons in Scotland. DESIGN AND SUBJECTS: Postal questionnaire
      survey of all practising vascular surgeons in Scotland (n = 40) identified from
      the list of members of the Vascular Society of Great Britain and Ireland.
      RESULTS: Most surgeons (30 of the 34 respondents, 88%) practise chemical lumbar
      sympathectomy. Their main indications are in line with current recommendations in
      relevant publications. Controversial areas include its use as an adjunct to
      operation and in treating diabetic feet. The procedure is done by vascular
      surgeons (16 of 34 respondents, 47%) and anaesthetists or radiologists (14 of the
      34 respondents, 41%). There is a wide variation in the technical aspects of the
      procedure. All respondents make a clinical assessment of outcome. CONCLUSION: The
      role of chemical lumbar sympathectomy is likely to remain controversial because
      of the lack of a valid prognostic marker, technical variability, and the fact
      that it is often used in elderly patients.

PMID- 10881949
TI  - Randomised trial of safety and efficacy of postoperative enteral feeding in
      patients with severe pancreatitis: preliminary report.
AB  - OBJECTIVE: To find out whether postoperative enteral feeding is safe and
      effective in patients with severe pancreatitis. DESIGN: Prospective randomised
      trial. SETTING: Teaching hospital, Latvia. SUBJECTS: 29 patients who had been
      operated on for severe pancreatitis. INTERVENTIONS: They were randomised to have
      either enteral nutrition and conventional intravenous fluids postoperatively (n =
      11), or conventional intravenous fluids only (n = 18). 17 additional patients who
      had had major abdominal operations for other conditions were also given enteral
      nutrition and intravenous fluids and comprised the control group. MAIN OUTCOME
      MEASURES: Nutritional intake, duration of stay in intensive care (ICU) and
      hospital morbidity, mortality, and outcome. RESULTS: 1 patient died of the 11
      given enteral nutrition combined with conventional intravenous fluids, compared
      with 5/18 given fluids only. The pattern of bowel transit in the fed group did
      not differ from that in the control group. CONCLUSION: Postoperative enteral
      nutrition seems to be safe and effective in patients with severe pancreatitis and
      may improve survival. Our results suggest that enteral and parenteral nutrition
      may complement each other in seriously ill patients.

PMID- 10881950
TI  - Should an appendix that looks 'normal' be removed at diagnostic laparoscopy for
      acute right iliac fossa pain?
AB  - OBJECTIVE: To find out whether the removal of the appendix from patients in whom
      laparoscopy for acute right iliac fossa pain shows no abnormality is justified to
      avoid the risk of missing acute appendicitis. PATIENTS: The records of patients
      who, between 1990 and 1997 had emergency laparoscopy for acute right iliac fossa
      pain were reviewed. Only those in whom laparoscopy had shown no abnormality and
      had not had the appendix removed were included in the study. METHODS: Outcome was
      assessed by telephone questionnaire to the patient, the general practitioner, or
      both. RESULTS: Emergency laparoscopy had been done for 254 patients. No
      abnormality was detected in 41. Full follow up was available on 34 patients
      (83%). 21 patients have remained entirely free of symptoms. Of the 13 patients
      who had recurrent symptoms, 2 subsequently had a histologically normal appendix
      removed, yet still had symptoms; 2 had a second laparoscopy that showed no
      abnormality; 5 had ultrasound; and 4 had colonoscopy or a barium enema
      examination. CONCLUSION: Removal of an appendix that looks 'normal' at emergency
      laparoscopy for right iliac fossa pain is unjustified.

PMID- 10881951
TI  - Primary lymphoma of the breast: unusual presentation of breast cancer.
AB  - OBJECTIVE: To investigate 4 cases of primary lymphoma of the breast and review
      previous studies in a search for any preoperative characteristics that could
      assist the diagnosis of lymphoma of the breast. DESIGN: Retrospective study.
      SETTING: University hospital, Israel. SUBJECTS: 4 women. MAIN OUTCOME MEASURES:
      Accurate diagnosis before operation. RESULTS: No special characteristics for
      early diagnosis of primary malignant lymphoma of the breast were found. The
      predominant involvement of right breast in primary lymphoma of the breast should
      be noted. CONCLUSIONS: Even though primary lymphoma of the breast is rare, there
      are no laboratory or imaging signs of early diagnosis. Excisional biopsy or Tru
      cut biopsy are the only correct methods of diagnosis.

PMID- 10881952
TI  - Laparoscopic or open cholecystectomy: a prospective randomised trial to compare
      postoperative pain, pulmonary function, and stress response.
AB  - OBJECTIVE: Open cholecystectomy (OC) has been superseded by laparoscopic
      cholecystectomy (LC) for the treatment of cholelithiasis, although this fashion
      has not been validated by prospective studies. Our aim was to compare the two
      techniques. DESIGN: Prospective, randomised, open study. SETTING: University
      hospital, Finland. PATIENTS: 49 patients who required cholecystectomy for
      cholelithiasis confirmed by ultrasound. INTERVENTIONS: 49 patients were randomly
      allocated to LC (n = 27) or OC (n = 22): 25 and 22, respectively, eventually had
      the operation. LC was done using a four-trocar technique, and OC through a
      transverse right subcostal incision, as short as possible. MAIN OUTCOME MEASURES:
      Length of hospital stay and the duration of the sick leave were the primary
      outcome measures. Secondary outcome measures were: postoperative pain evaluated
      by visual analogue scale (VAS) and the need for opioids; pulmonary function
      measured by forced vital capacity (FVC), forced expiratory volume in one second
      (FEV1), peak flow velocity (PEFV), and arterial oxygen tension (PaO2), and
      endocrine stress measured by plasma catecholamines, cortisol and glucose
      concentrations. RESULTS: The median (range) hospital stay was significantly
      shorter after LC than OC, being 2.0 (1-15) compared with 4.5 (2-19) days p <
      0.01. The duration of sick leave was also significantly shorter after LC than OC,
      being 14 (7-17) compared with 29 (4-34), p < 0.01. Patients had significantly
      less postoperative pain after LC than OC as reflected by the need for opioids.
      Pulmonary function and arterial oxygen tension deteriorated significantly less
      after LC than OC. The stress response was equal. There were three documented
      complications, one pneumonia after LC and two wound infections after OC.
      CONCLUSIONS: LC gives significantly better results in terms of less postoperative
      pain, better pulmonary function, better arterial oxygenation, and shorter
      hospital stay and duration of sick leave.

PMID- 10881953
TI  - Santoriniplasty in the management of symptomatic pancreas divisum.
AB  - OBJECTIVE: To assess the long-term results of sphincteroplasty of the minor
      papilla in a series of patients with symptomatic pancreas divisum. DESIGN:
      Retrospective study. SETTING: University hospital, UK. SUBJECTS: 6 consecutive
      patients with recurrent acute pancreatitis thought to be caused by pancreas
      divisum. INTERVENTIONS: Surgical enlargement of the minor papilla of Santorini
      (Santoriniplasty). MAIN OUTCOME MEASURES: The effectiveness of the procedure in
      preventing further episodes of acute pancreatitis and controlling chronic
      intermittent pancreatic pain, outside documented attacks of pancreatitis.
      RESULTS: Median follow up was 4 years (range: 1-6). The procedure was effective
      in preventing further episodes of recurrent acute pancreatitis (in all patients)
      but not uniformly good in controlling chronic pancreatic pain (good: 2/6,
      moderate: 1/6, poor: 3/6). CONCLUSION: The prevention of further attacks of acute
      pancreatitis by Santoriniplasty indicates that a short term favourable clinical
      outcome may be achieved by improving drainage of the pancreatic duct through the
      stenosed minor papilla. Poor pain control may indicate early parenchymal changes
      or that unsuitable patients had been selected for surgical intervention. At
      present, there are no objective tests of pancreatic function that can predict
      which patients are most likely to benefit from Santoriniplasty. Prospective
      studies with more patients followed up for longer periods of time are needed
      before the role of the surgical drainage in symptomatic pancreas divisum can be
      clearly defined.

PMID- 10881954
TI  - Perforated peptic ulcer: laparoscopic approach.
AB  - OBJECTIVES: To examine the suitability of a laparoscopic approach for treatment
      of perforated peptic ulcer. DESIGN: Retrospective non-randomised study. SETTING:
      District Community Hospital. METHODS: 30 patients who presented with perforated
      peptic ulcers between November 1992 and October 1997 INTERVENTIONS: 16 patients
      were operated on laparoscopically, and 14 by open operation (as there was no
      surgeon available with laparoscopic experience). MAIN OUTCOME MEASURES: Morbidity
      and mortality. RESULTS: The laparoscopic operation was successful in all but one
      patient, whose operation was converted to an open procedure because we could not
      see the ulcer adequately. Duration of operation and postoperative nasogastric
      aspiration, analgesic requirements, hospital stay, morbidity, and mortality were
      similar in the two groups. CONCLUSIONS: Laparoscopic repair of a perforated
      peptic ulcer is safe in selected patients in whom a laparotomy should be avoided.

PMID- 10881955
TI  - Establishment of an immunocompetent nipple valve anastomosis to prevent faecal
      reflux after ileocolic resection in dogs.
AB  - OBJECTIVE: To construct an immunocompetent nipple valve anastomosis (NVA) to
      exclude faecal reflux and compare it with an end-to-end anastomosis to see if it
      would prevent recurrent inflammation caused by intraluminal bacterial antigens in
      Crohn's disease. DESIGN: Laboratory study. SETTING: Teaching hospital, Germany.
      ANIMALS: Two groups of six beagle dogs each of which had NVA or end-to-end
      anastomosis. INTERVENTIONS: Construction of a NVA by stapling the telescoped
      nipple, and replacing the ileal mucosa on the valve by colonic mucosa; end-to-end
      anastomosis. MAIN OUTCOME MEASURES: Radiological, bacteriological, angiographic,
      and morphometric results. RESULTS: Absolute retrograde pressure-competence and
      free orthograde permeability of the NVA resulted in significantly lower
      intestinal bacterial counts compared with the end-to-end anastomosis (p < 0.05).
      Transposition of colonic mucosa was successful as demonstrated by
      revascularisation from the ileal nipple and looked normal on morphometry.
      CONCLUSION: If NVA were constructed in patients with Crohn's disease, recurrences
      should be prevented, which would verify the immunopathogenetic hypothesis of new
      inflammation.

PMID- 10881956
TI  - Umbilical herniorrhaphy in cirrhotic patients: a safe approach.

PMID- 10881957
TI  - New modified reconstruction in a duodenum-preserving resection of the head of the
      pancreas.

PMID- 10881958
TI  - Ultrasonic diagnosis of strangulated obturator hernia.

PMID- 10881959
TI  - Intestinal obstruction by a large gallstone in the rectum: successful catheter
      aided extraction.

PMID- 10881960
TI  - Intrathoracic diverticulum caused by a leiomyoma: a rare case of spontaneous
      oesophageal rupture.

PMID- 10881961
TI  - The current status of tardive dyskinesia.
AB  - OBJECTIVE: This paper aims to provide an overview of the current knowledge on
      neuroleptic-induced tardive dyskinesia (TD) in relation to its clinical features,
      risk factors, pathophysiology and management. METHOD: The published literature
      was selectively reviewed and assessed. RESULTS: Tardive diskinesia is a common
      neurological side-effect of neuroleptic medication, the cumulative incidence of
      which increases with increasing duration of treatment. Its clinical
      manifestations are diverse and subsyndromes have been described. Many risk
      factors for TD are now recognised, but increasing age remains pre-eminent as a
      risk factor. The pathophysiology of TD is not completely understood. Of the
      neurotransmitter hypotheses, the dopamine receptor supersensitivity hypothesis
      and the gamma-aminobutyric acid insufficiency hypothesis are the main contenders.
      There is increasing recognition that TD may in fact be caused by neuroleptic
      induced neuronal toxicity through free radical and excitotoxic mechanisms. The
      occurrence of spontaneous dyskinesias in schizophrenic patients and even healthy
      subjects suggests that neuroleptics act on a substratum of vulnerability to
      dyskinesia. As no effective treatment for TD is available, the primary emphasis
      is on prevention. Many drugs can be tried to reduce symptoms in established
      cases. The increasing use of atypical neuroleptics has raised the possibility of
      a lower incidence of TD in the future. CONCLUSIONS: After four decades of
      clinical recognition, the pathophysiology of TD is still not understood and no
      effective treatment is available. Its prevention with the optimal usage of
      currently available drugs and regular monitoring of patients on long-term
      neuroleptic treatment remain the best strategies to reduce its impact.

PMID- 10881962
TI  - The epidemiology of suicide and attempted suicide among young Australians.
AB  - OBJECTIVE: This paper summarises a report to the NHMRC the objectives of which
      were to review research into the epidemiology of youth suicide in Australia and
      identify gaps in research. METHOD: Literature searches were conducted. A limited
      amount of new data analysis was included to shed light on reliability issues of
      official Australian suicide data. RESULTS: The review examined suicide data
      systems, including issues to do with coroners, the Australian Bureau of
      Statistics and alternative systems. The epidemiological areas reviewed included:
      all ages, youth, age and gender, geographical, socioeconomic, marital,
      indigenous, migrants, suicides in custody and gay and lesbian suicides.
      CONCLUSION: While much is known about the epidemiology of youth suicide, much
      remains to be clarified. Study of indigenous issues is perhaps the most neglected
      area; study of family issues may be potentially be the most productive.

PMID- 10881963
TI  - Preventive interventions for youth suicide: a risk factor-based approach.
AB  - OBJECTIVE: This review draws on current knowledge of risk for youth suicide to
      categorize strategies for intervention. Its goal is to identify areas of
      'research need' and to provide an evidence base to identify 'best buy' preventive
      interventions for youth suicide. METHOD: The design, development, implementation
      and evaluation of prevention strategies ranging from clinical interventions to
      population-based universal approaches are considered within five risk factor
      domains: individual, family, community, school and peer. RESULTS: There is a
      paucity of evidence on the effects of interventions targeting depression and
      suicidal behaviour. Nevertheless, there are effective indicated, selective and
      universal interventions for important risk factors for depression and suicidal
      behaviour. Little evidence has emerged to support the efficacy of some
      traditional approaches to suicide prevention, such as school based suicide
      education programs and telephone hotlines. CONCLUSIONS: Youth suicide prevention
      strategies in Australia have generally employed traditional approaches that focus
      on clinical interventions for self-harmers, restricting access to lethal means,
      providing services to high risk groups and enhancing general practitioner
      responses. Both program development and research evaluation of interventions for
      many important risk and protective factors for suicide have been neglected.

PMID- 10881964
TI  - Cohort trends in youth suicide in Australia 1964-1997.
AB  - OBJECTIVE: This paper examines trends in the rate of suicide among young
      Australians aged 15-24 years from 1964 to 1997 and presents an age-period-cohort
      analysis of these trends. METHOD: Study design consisted of an age-period-cohort
      analysis of suicide mortality in Australian youth aged between 15 and 24 for the
      years 1964-1997 inclusive. Data sources were Australian Bureau of Statistics data
      on: numbers of deaths due to suicide by gender and age at death; and population
      at risk in each of eight birth cohorts (1940-1944, 1945-1949, 1950-1954, 1955
      1959, 1960-1964, 1965-1969, 1970-1974, and 1975-1979). Main outcome measures were
      population rates of deaths among males and females in each birth cohort
      attributed to suicide in each year 1964-1997. RESULTS: The rate of suicide deaths
      among Australian males aged 15-24 years increased from 8.7 per 100,000 in 1964 to
      30.9 per 100,000 in 1997, with the rate among females changing little over the
      period, from 5.2 per 100,000 in 1964 to 7.1 per 100,000 in 1997. While the rate
      of deaths attributed to suicide increased over the birth cohorts, analyses
      revealed that these increases were largely due to period effects, with suicide
      twice as likely among those aged 15-24 years in 1985-1997 than between 1964 and
      1969. CONCLUSIONS: The rate of youth suicide in Australia has increased since
      1964, particularly among males. This increase can largely be attributed to period
      effects rather than to a cohort effect and has been paralleled by an increased
      rate of youth suicides internationally and by an increase in other psychosocial
      problems including psychiatric illness, criminal offending and substance use
      disorders.

PMID- 10881965
TI  - Methods of youth suicide in New Zealand: trends and implications for prevention.
AB  - OBJECTIVE: One commonly suggested approach to reducing suicide is to restrict
      access to potentially lethal means of suicide. This paper summarises recent
      trends in methods of suicide among young people in New Zealand and examines the
      feasibility of suicide prevention through restricting access to methods of
      suicide. METHOD: Data derived from official mortality statistics were used to
      examine trends, from 1977 to 1996, in methods of suicide among young people aged
      15-24 years. RESULTS: During the last two decades, male youth suicide rates in
      New Zealand doubled, from 20.3 per 100,000 in 1977 to 39.5 per 100,000 in 1996.
      This increase was accounted for, almost entirely, by increased use of hanging
      (71% of total increase) and vehicle exhaust gas (26% of total increase). Suicide
      rates among young females also increased, from 4 per 100,000 in 1977 to 14.3 per
      100,000 in 1996. As for males, the increased female suicide rate was largely
      accounted for by increased rates of hanging and vehicle exhaust gas. CONCLUSIONS:
      The marked increases in rates of youth suicide in New Zealand during the past two
      decades are accounted for, almost wholly, by increases in rates of suicide by
      hanging and, to a lesser extent, vehicle exhaust gas. In 1996 the majority
      (79.7%) of youth suicides were accounted for by these two methods: hanging
      (61.5%) and vehicle exhaust gas (18.2%). Both methods are widely available and
      difficult to restrict, implying that limiting access to means of suicide is a
      strategy which is unlikely to play a major role in reducing suicidal behaviour
      among young people in New Zealand.

PMID- 10881966
TI  - Risk factors for suicide and attempted suicide among young people.
AB  - OBJECTIVE: Suicide rates in young people have increased during the past three
      decades, particularly among young males, and there is increasing public and
      policy concern about the issue of youth suicide in Australia and New Zealand.
      This paper summarises current knowledge about risk factors for suicide and
      suicide attempts in young people. METHOD: Evidence about risk factors for
      suicidal behaviour in young people was gathered by review of relevant English
      language articles and other papers, published since the mid-1980s. RESULTS: The
      international literature yields a generally consistent account of the risk
      factors and life processes that lead to youth suicide and suicide attempts. Risk
      factor domains which may contribute to suicidal behaviour include: social and
      educational disadvantage; childhood and family adversity; psychopathology;
      individual and personal vulnerabilities; exposure to stressful life events and
      circumstances; and social, cultural and contextual factors. Frequently, suicidal
      behaviours in young people appear to be a consequence of adverse life sequences
      in which multiple risk factors from these domains combine to increase risk of
      suicidal behaviour. CONCLUSIONS: Current research evidence suggests that the
      strongest risk factors for youth suicide are mental disorders (in particular,
      affective disorders, substance use disorders and antisocial behaviours) and a
      history of psychopathology, indicating that priorities for intervening to reduce
      youth suicidal behaviours lie with interventions focused upon the improved
      recognition, treatment and management of young people with mental disorders.

PMID- 10881967
TI  - Factors associated with repeat suicide attempts among adolescents.
AB  - OBJECTIVE: To determine potential risk factors associated with repeat suicide
      attempts among adolescents. METHOD: Retrospective medical record review of all
      patients aged 13-20 years who presented to the emergency department at an inner
      city tertiary hospital after attempted suicide between 1994 and 1996. Subjects
      were identified using the International Classification of Diseases (ICD-9) codes
      E950.0 to E959.9 for attempted suicide. Study variables included demographic
      parameters, chronic medical conditions/illnesses, psychiatric and substance abuse
      disorders, history of sexual abuse and previous and subsequent suicide attempts.
      Variables univariately associated with repetition at p < 0.25 were entered into a
      multiple regression analysis. RESULTS: Eighty seven per cent of patients
      presented with a drug overdose. Seventy-six per cent of all subjects attempted
      suicide in the context of a dispute or relationship break-up. At least one
      psychiatric disorder was present in 76% of subjects at the index attempt. The
      most frequently diagnosed disorders were depression (45.5%) and drug (34%) and
      alcohol abuse (27%). Variables predicting repetition within 12 months were drug
      (OR = 3.891, p = 0.02) and alcohol abuse (OR = 3.56, p = 0.05), non-affective
      psychotic disorders (OR = 3.81, p = 0.04), and chronic medical conditions/illness
      (OR = 3.29, p = 0.03). A history of sexual abuse was almost significant (OR =
      3.03, p = 0.06). CONCLUSIONS: Adolescents most likely to re-attempt suicide with
      12 months present with either substance abuse, non-affective psychotic disorders,
      chronic medical conditions, or a history of sexual abuse. All adolescents with a
      possible suicide attempt should receive a comprehensive mental health and
      psychosocial assessment. Closer scrutiny of the role of chronic illnesses and
      sexual abuse in both future research and clinical management is urged. A broad
      based, multidisciplinary intervention approach is recommended.

PMID- 10881968
TI  - Posttraumatic stress disorder and emotional problems in children following motor
      vehicle accidents: an extended case series.
AB  - OBJECTIVE: The prevalence of posttraumatic stress disorder (PTSD) and general
      psychopathology in children following motor vehicle accidents (MVA) was
      investigated. METHOD: Twenty-six subjects aged 8-13 years presenting to an
      emergency department following an MVA were assessed 3 months after the accident
      using a standard clinical psychiatric assessment, a structured research interview
      and self- and parent-report questionnaires. RESULTS: A higher prevalence of
      psychopathology was seen in the sample compared with community controls. Self
      report of PTSD symptoms revealed 22% subjects in the moderate or severe PTSD
      range and 35% of mild severity. There was significant concordance between self
      report PTSD scores and a clinical diagnosis of PTSD. Perception of threat and the
      internalising subscale on the Child Behaviour Checklist were significantly
      correlated with PTSD scores. CONCLUSIONS: PTSD and other symptoms of emotional
      distress are common following MVAs. The clinical and public health implications
      are discussed, and areas for further research highlighted.

PMID- 10881969
TI  - Family environment in attention deficit hyperactivity, oppositional defiant and
      conduct disorders.
AB  - OBJECTIVE: This study aims to ascertain whether there were differences in family
      environment among patients with attention deficit hyperactivity disorder (ADHD),
      oppositional defiant disorder and conduct disorder. METHOD: The records of 233
      patients, selected for high or low scores on a scale that taps ADHD symptoms,
      were reviewed by three clinicians who made DSM-IV diagnoses and rated the family
      environment with the Global Family Environment Scale (GFES). Self-report data
      obtained from the parent and child versions of the Child Behaviour Checklist were
      also used. The quality of the family environment was then compared between the
      various diagnostic groups. RESULTS: A poorer family environment was associated
      with conduct disorder and oppositional defiant disorder and predicted a worse
      outcome (e.g. admission to a non-psychiatric institution, drug and alcohol
      abuse). Quality of the family environment did not vary according to ADHD
      diagnosis or gender. CONCLUSIONS: There seems to be no association between the
      quality of the family environment and a diagnosis of ADHD among referred
      adolescents. However, there is an association with conduct disorder.
      Interventions that improve family environment in the early years of life may
      prevent the development of conduct problems.

PMID- 10881970
TI  - Reactive psychoses revisited.
AB  - OBJECTIVE AND METHOD: This paper describes the overlap between reactive
      (psychogenic) psychosis and other brief psychotic episodes, and explores the
      gradual disappearance of reactive psychoses as a distinct nosological entity from
      international classifications. Clinical and conceptual issues concerning reactive
      psychosis are examined on the basis of a critical review of major classical and
      modern papers. A brief illustrative case history is also provided. RESULTS:
      Reactive psychoses are conceptualised as severe disturbances of mental state, on
      occasion chameleon-like in their shifting form and content, arising in response
      to a stressful event or life situation. Reactive psychoses have an abrupt onset
      and usually run their course to complete resolution in a matter of days or weeks.
      Precipitants include overwhelming fear, threat of imminent destruction, social
      isolation (as can occur with imprisonment, immigration or deafness), bereavement
      and intense sexual or interpersonal conflicts. The emergence of a reactive
      psychosis usually occurs against the background of a predisposing vulnerability
      in terms of personality disorder, organic impairment, or a history of sensitising
      experiences, occasionally operating in combination. CONCLUSIONS: The increasing
      failure to recognise reactive psychoses diminishes clinical psychiatry because it
      removes an important opportunity for understanding mental disorder in terms of an
      integration, and totalisation, of developmental history, psychological makeup,
      social context and current realities, and in so doing lessens our awareness of
      the links between psychosis and our common humanity.

PMID- 10881971
TI  - Cannabis, vulnerability, and the onset of schizophrenia: an epidemiological
      perspective.
AB  - OBJECTIVE: Second to alcohol, cannabis is the most frequently misused substance
      among patients with schizophrenia. The aim of this paper is to examine at early
      onset of psychosis whether the high comorbidity of schizophrenia and cannabis
      abuse is due to a causal relationship between the two disorders. Previous studies
      have mostly included chronic patients or samples with mixed stages of the
      psychotic illness. METHOD: In a German catchment area with a population of
      1,500,000, a representative first-episode sample of 232 patients with
      schizophrenia was included in the Age, Beginning and Course of Schizophrenia
      Study. By means of a structured interview, the Retrospective Assessment of the
      Onset of Schizophrenia, the onset and course of schizophrenic symptoms and of
      substance abuse was systematically assessed retrospectively. Information given by
      relatives validated the patients' reports. RESULTS: Thirteen per cent of the
      sample had a history of cannabis abuse, which was twice the rate of matched
      normal controls. Male sex and early symptom onset were major risk factors. While
      cannabis abuse almost always preceded the first positive symptoms of
      schizophrenia, the comparison of the onset of cannabis abuse and of the first
      (prodromal) symptoms of schizophrenia differentiated three approximately equal
      groups of patients: group 1 had been abusing cannabis for several years before
      the first signs of schizophrenia emerged, group 2 experienced the onset of both
      disorders within the same month, and group 3 had started to abuse cannabis after
      the onset of symptoms of schizophrenia. CONCLUSIONS: The vulnerability-stress
      coping model of schizophrenia suggests possible interpretations of these
      findings. Group 1 might suffer from the chronic deteriorating influence of
      cannabis reducing the vulnerability threshold and/or coping resources. Group 2
      consists of individuals which are already vulnerable to schizophrenia. Cannabis
      misuse then is the (dopaminergic) stress factor precipitating the onset of
      psychosis. Group 3 uses cannabis for self-medication against (or for coping with)
      symptoms of schizophrenia, particularly negative and depressive symptoms. These
      patients probably learn to counterbalance a hypodopaminergic prefrontal state by
      the dopaminergic effects of cannabis. The implications of these very preliminary
      results include issues of treatment and prognosis, but replication studies are
      needed.

PMID- 10881972
TI  - Deinstitutionalisation for long-term mental illness: a 2-year clinical
      evaluation.
AB  - OBJECTIVE: The closure of a long-stay psychiatric hospital in Sydney caused the
      transfer of an initial 40 very long-term patients to four community residences,
      each with 10 beds, for a continuing process of deinstitutionalisation. Community
      psychiatric service support and 24-h supervision were provided. This paper
      describes the residents' clinical progress which was assessed over a 2-year
      period. METHOD: This study employed a quasi-experimental longitudinal design.
      Evaluation commenced prior to discharge and continued for 2 years following
      community relocation using the Brief Psychiatric Rating Scale, Life Skills
      Profile, Social Behaviour Scale, Montgomery Asberg Depression Rating Scale and
      Quality Of Life measures. Readmission, demographic, case history and medication
      data were also collected. RESULTS: Of the 40 patients initially transferred to
      the community, seven required long-term readmission to hospital (either prior to
      or after amalgamation) and one patient died of medical causes. Additional
      patients transferred from the hospital to the community following the
      readmissions. Three of these additional patients had achieved a 2-year community
      tenure during the study period and were included in the clinical evaluation. The
      35 residents in total who remained in the community for 2 years, demonstrated a
      significant improvement in psychotic symptoms, without significant change in the
      level of neuroleptic medication. Importantly, the 2 years of community living
      resulted in a significant increase in the residents' life satisfaction. There
      were no statistically significant changes in residents' living skills, depressive
      symptoms or social behaviour problems over the 2 years, indicative of the need
      for supervision and community service support following deinstitutionalisation.
      Over the 2-year period, some 37% of the residents required temporary readmission.
      CONCLUSION: This study demonstrates the clinical effectiveness of
      deinstitutionalisation, when planned within a mental health system with adequate
      community resources.

PMID- 10881973
TI  - Deinstitutionalisation for long-term mental illness: an ethnographic study.
AB  - OBJECTIVE: Deinstitutionalisation of seriously mentally ill people in the
      developed world, including Australia, has occurred since the middle of this
      century. Evaluation of the effects of this change on the lives of individuals is
      of paramount importance to ensure that policies are acceptable and effective.
      Increasingly, multifaceted studies are considered essential for comprehensive
      health research. The qualitative aspect of this study complements the clinical
      and economic components. METHOD: An ethnographic approach enabled contextual,
      qualitative data to be gathered from within the social world of 47 hospital
      residents as they moved to the community. A social anthropologist acting
      explicitly as a participant observer undertook fieldwork over two and a half
      years both pre- and post-discharge. Qualitative data were collected, stored and
      analysed separately from quantitative and economic data. RESULTS: Ethnographic
      findings generally supported and, in many cases, mirrored clinical results. Of
      the total cohort of 47 patients transferred to the community, the 40 who continue
      to live outside of hospital all reported a preference for community living. The
      importance of freedom and simple liberties cannot be underestimated as factors
      that enabled this resilient group of people to work creatively through difficult
      periods. CONCLUSION: Properly planned and resourced deinstitutionalisation not
      only maintains people with a prolonged mental illness outside of hospital, it
      also enhances their quality of life. Subjective descriptive material focusing on
      personal experiences adds meaning to quantitative research data allowing health
      professionals to more fully understand the implications of health policy on the
      lives of individuals.

PMID- 10881974
TI  - Deinstitutionalisation for long-term mental illness: cost differences in hospital
      and community care.
AB  - OBJECTIVE: This project studied the cost analysis of psychiatric hospital and
      then community care for long-stay patients with chronic mental illness discharged
      during the closure of a psychiatric hospital in Sydney. METHOD: Expenditure and
      income data in both settings were collected. Costs were analysed on an occupied
      bed-day basis. RESULTS: The hospital setting cost more per patient per day
      compared with the various community costs which were one-third to one-half of the
      comparable hospital costs. CONCLUSIONS: The analysis demonstrated overall that
      hospital care was nearly twice as expensive as care in the community setting. The
      factors which may have influenced, although not necessarily altered, the
      substance of the findings largely related to 'organisational efficiency'. The
      mental hospital as an older, more rigid system was likely to be less efficient
      than the newer community service provision which was under intensive scrutiny
      both clinically and financially by all interested parties.

PMID- 10881975
TI  - The development of clinical indicators for a consultation-liaison service.
AB  - OBJECTIVE: The aim of this paper is to describe the development and
      implementation of clinical indicators in the consultation-liaison service at
      Royal Melbourne Hospital (RMH). METHOD: A working party lead by the University of
      Melbourne was established in 1998 to develop clinical indicators and a database
      for the RMH consultation-liaison service. Core parameters for measuring service
      functioning and six clinical indicators were developed. The system was
      implemented using a data collection form and computerised database operating
      within a system of regular clinical reviews. RESULTS: The clinical indicators,
      database and review system were found to be a feasible, useful and efficient
      addition to a consultation-liaison service at a major general hospital.
      CONCLUSIONS: Clinical indicators may be used within specialist psychiatry
      services to enhance clinical care and aid in service development and teaching.

PMID- 10881976
TI  - The reliability and validity of the Health of the Nation Outcome Scales:
      validation in relation to patient derived measures.
AB  - OBJECTIVE: The Health of Nation Outcome Scales (HoNOS) was developed to assess
      mental health outcomes. The aim of the studies is to examine the psychometric
      properties, reliability and validity of the HoNOS. METHOD: Three studies were
      conducted within St John of God Hospitals in New South Wales, Australia. They
      examined the reliability and the validity of the HoNOS. The first study examined
      the interrater reliability of the HoNOS, before and after staff training in the
      use of the HoNOS. The second study examined the validity of the HoNOS with the
      Symptom Checklist 90 Revised (SCL90-R) and the third study examined the validity
      of the HoNOS with the Short-Form 36 (SF-36). RESULTS: The first study showed an
      improvement in the interrater reliability (IRR) of the HoNOS due to training.
      However, a generally unsatisfactory IRR (range 0.50-0.65) was achieved. The
      second study found no correlation between the SCL90-R and the HoNOS on admission
      (r = 0.04) and discharge (r = 0.06). The third study found no significant
      correlation between the Mental Component Score of the SF-36 and the HoNOS on
      admission (r = -0.033) nor on discharge (r = -0.104). CONCLUSIONS: The HoNOS has
      at best moderate interrater reliabilities. Further, the validity of the HoNOS is
      under question, that is, it does not correlate with a major measure of mental
      health symptoms, nor with a major measure of health status. As such, it is
      concluded that the psychometric properties of the HoNOS do not warrant its use as
      a routine measure.

PMID- 10881977
TI  - The Health of the Nation Outcome Scales: validating factorial structure and
      invariance across two health services.
AB  - OBJECTIVE: The Health of the Nation Outcome Scale (HoNOS) was developed in the
      mid-1990s as an inclusive and comprehensive instrument to measure patient
      outcomes in four main factors: behaviour, impairment, symptoms and social
      problems. This paper attempts to investigate whether similar health services rate
      the HoNOS with equivalent psychometric calibration. METHOD: The purpose of this
      study was to test for invariant construct interpretation of the instrument across
      two equivalent health services, using simultaneous confirmatory factor analysis.
      RESULTS: Although the four-factor model of the HoNOS was confirmed, structural
      non-invariance occurred, casting doubt on the equivalent interpretability and
      generalisability of the instrument across similar heath services. CONCLUSIONS:
      Over-inclusiveness, lack of specificity and questionable independence of
      observations may have contributed to the non-invariant factor structure between
      the two health services. Such results shed some doubt on the ability of the HoNOS
      and like observational instruments to provide equivalent comparisons between
      health services.

PMID- 10881978
TI  - Nosological implications of psychotic symptoms in patients with established
      posttraumatic stress disorder.
AB  - OBJECTIVE: We describe three patients with chronic posttraumatic stress disorder
      (PTSD) who later developed psychotic symptoms. The nosological implications are
      discussed. CLINICAL PICTURE: All three patients had no prior history of psychotic
      illness. The content of the psychotic symptoms was restricted to core features of
      the traumatic experiences which initially led to PTSD. TREATMENT: The patients
      received low-dose antipsychotic medications in addition to other treatments for
      PTSD and/or depression. OUTCOME: All three patients developed severe
      extrapyramidal side effects, particularly akathisia, and discontinued drug
      treatment. CONCLUSION: Psychotic symptoms occasionally can complicate chronic
      PTSD, but uncertainty remains about their aetiology and nosological status.

PMID- 10881979
TI  - Responses to 'the Presidential Address'. Health-care funding: our choice.

PMID- 10881980
TI  - Should we be flying high or grounded in clinical practice?

PMID- 10881981
TI  - Lamotrigine augmentation of serotonin re-uptake inhibitors in obsessive
      compulsive disorder.

PMID- 10881982
TI  - Age as substitute of age at onset in mood disorders studies.

PMID- 10881983
TI  - Psychiatrist attitudes toward herbal remedies.

PMID- 10881984
TI  - 'Obsessive-compulsive psychosis'.

PMID- 10881985
TI  - Gasoline inhalation dependence and bipolar disorder.

PMID- 10881986
TI  - My twin has been diagnosed with bipolar affective disorder. How likely am I to
      get it?

PMID- 10881987
TI  - Other clinical uses of olanzapine.

PMID- 10881988
TI  - Adjunctive risperidone treatment in patients with 'clozapine-resistant
      schizophrenia'.

PMID- 10881989
TI  - 'Patient' or 'client'?

PMID- 10881990
TI  - Risperidone in disorganised schizophrenia.

PMID- 10881991
TI  - Binding of the human papillomavirus type 16 E7 oncoprotein and the adeno
      associated virus Rep78 major regulatory protein in vitro and in yeast and the
      potential for downstream effects.
AB  - OBJECTIVE: Both human papillomavirus (HPV) and adeno-associated virus (AAV) are
      common anogenital viruses and likely co-infect the epithelium in vivo. However,
      whereas HPVs are positively associated with cervical cancer, AAV appears to be
      negatively associated. In tissue culture, AAV-encoded Rep78--which is essential
      for AAV--inhibits gene expression and oncogenic transformation by HPV-16/18 and
      bovine papillomavirus type 1. Here we observed whether the HPV-16 E7 oncoprotein
      might recognize and bind Rep78. Further, upon finding Rep78-E7 binding, we
      investigated some of the potential downstream effects such an interaction might
      have. E7 is capable of recognizing a variety of proteins, including RB105, TATA
      box-binding protein (TBP), TBP-associated factor (TAF)(II)110, E2F, cyclins A and
      D, and c-jun. Some of these interactions are likely responsible for E7's cancer
      promoting activity. STUDY DESIGN/METHODS: Rep78-E7 interaction was investigated
      in vitro by West(far)-Western and affinity chromatography analysis and in vivo in
      living yeast by the GAL4 two-hybrid cDNA assay. Mapping of the E7 binding domain
      within Rep78 was carried out using a series of amino- and carboxy-truncated Rep78
      proteins in a West(far)-Western assay. Downstream effects of the interaction were
      analyzed by competitive affinity chromatography (protein-protein) and competitive
      electrophoretic mobility shift assay (protein-DNA). RESULTS: E7 and Rep78 were
      found to interact both in vitro and in vivo (yeast) in all assays attempted. The
      E7 binding domain within Rep78 was found to reside within amino acids 121-370.
      Regarding downstream effects of this interaction, Rep78 was found to mildly
      inhibit E7-TAF(II)110 and E7-RB105 interaction in vitro but to have little affect
      on E7-TBP interaction. Finally, it was found that E7 was able to affect Rep78's
      interaction with AAV's terminal repeat (TR) DNA in vitro, reducing the formation
      of the largest sized Rep78-TR complexes in a dosage-dependent manner.
      CONCLUSIONS: These data suggest that the Rep78-E7 interaction may have
      repercussions for both viruses. The Rep78-E7 interaction may be a second
      mechanism, in addition to Rep78 regulation of the p97 promoter, by which AAV
      inhibits HPV-16 oncogenic transformation. These data also suggest that HPV-16 may
      affect the AAV life cycle by altering Rep78-TR interaction.

PMID- 10881992
TI  - Epstein-Barr virus-infected B-chronic lymphocyte leukemia cells express the
      virally encoded nuclear proteins but they do not enter the cell cycle.
AB  - OBJECTIVES: To understand the mechanism for the refractoriness of B-chronic
      lymphocyte leukemia (B-CLL) cells for EBV-induced immortalization. STUDY
      DESIGN/METHODS: Cells from four B-CLL patients were infected with Epstein-Barr
      virus (EBV). Noninfected and infected aliquots were exposed to CD40L. Five days
      later, the cultures were analyzed for cell survival, activation, DNA synthesis,
      and expression of EBV-encoded and of cellular regulatory proteins retinoblastoma
      (Rb), p53, recombinant sequence binding protein (RBP)Jk, and PU.1. The proteins
      were detected by immunoblotting and by immunofluorescence. RESULTS: A proportion
      of the cells were activated and expressed Epstein-Barr nuclear antigens (EBNAs)
      and elevated Rb level but not latent membrane protein (LMP)-1 and p53. They did
      not enter the cell cycle. Exposure to CD40L induced DNA synthesis but it did not
      modify the expression of the EBNAs. CONCLUSIONS: The virus could activate CLL
      cells, but the full course of the early events that leads to immortalization--as
      seen in normal B cells--did not proceed beyond a certain point. Compared to B
      lymphocytes, the critical point is between activation and initiation of the cell
      cycle.

PMID- 10881993
TI  - Antibody spectrum against the viral transactivator protein in patients with human
      immunodeficiency virus type 1 infection and Kaposi's sarcoma.
AB  - We analyzed patterns of antibody response to recombinant transactivator protein
      (human Immunodeficiency virus type 1 [HIV-1] tat) in serum samples from HIV-1
      negative subjects (n = 60), HIV-1-infected asymptomatic patients (n = 20), HIV-1
      infected patients with Kaposi's sarcoma (n = 25), and patients with Kaposi's
      sarcoma without HIV-1 infection. None of the healthy subjects possessed anti-tat
      immunoglobulin G (IgG) in their serum. All asymptomatic patients with HIV-1
      infection were anti-tat IgG-positive. Epitope mapping revealed that these sera
      had anti-tat IgG to all the functional domains of tat protein. Histochemical
      studies on lymph nodes from five asymptomatic HIV-1-infected patients showed
      that, in all cases, tat-positive cells were present within the germinal center at
      the stage of follicular fragmentation containing immunoblasts and small
      lymphocytes. Of the 25 HIV-1-infected patients with Kaposi's sarcoma, 4 were anti
      tat IgG-positive; however, the epitope analysis revealed that IgG to functional
      domains of tat protein--in particular to transactivating response element (TAR)
      binding site--were absent. All patients with Kaposi's sarcoma without HIV-1
      infection were anti-tat IgG-negative. Presence or absence of anti-tat IgG and a
      prevalence of different antibody profiles in different groups of patients
      indicated the pathophysiologic role of tat protein. Thus, a passive immunization
      with anti-tat IgG could be a useful strategy to influence the pathophysiologic
      state of the disease.

PMID- 10881994
TI  - Deletions in the beta3-beta4 hairpin loop of HIV-1 reverse transcriptase are
      observed in HIV-1 isolated from subjects during long-term antiretroviral therapy.
AB  - OBJECTIVES: To examine the effect of in-frame deletions in human immunodeficiency
      virus type 1 (HIV-1) reverse transcriptase (RT) on plasma viremia and phenotypic
      resistance to antiretroviral drugs. STUDY DESIGN/METHODS: Plasma HIV-1 RNA was
      isolated from 168 antiretroviral therapy-experienced subjects for quantification
      of plasma viremia, RT sequence analysis, and phenotypic resistance assays.
      RESULTS: Four patients were found to harbor HIV-1 strains possessing in-frame, 3
      nucleotide deletions at RT codons 67, 69, and 70. In these subjects, phenotypic
      resistance and high plasma viremia were observed only in a background of multiple
      resistance mutations. A recombinant virus engineered with an in-frame deletion of
      RT codon 67 did not have increased resistance to nucleoside reverse transcriptase
      inhibitors (NRTIs). CONCLUSIONS: Selection for deletions within the beta3-beta4
      hairpin loop of the HIV-1 RT is an uncommon event most likely to occur in
      subjects with long-term antiretroviral experience. The codon 67 deletion does not
      appear to cause increased phenotypic resistance or increased viremia in the
      absence of concomitant RT mutations.

PMID- 10881995
TI  - Single- and multidrug resistance mutations to reverse transcriptase and protease
      inhibitors: human immunodeficiency virus type 1-infected patients from two
      geographical areas in Spain. Spanish Groups for Antiretroviral Resistance
      Studies.
AB  - OBJECTIVES: To describe the prevalence of genotypic resistance mutations,
      including single and multidrug resistance (MDR) to reverse transcriptase (RT) and
      protease (PR) inhibitors in treated and untreated patients from two geographical
      areas in Spain (Madrid and Galicia). STUDY DESIGN/METHODS: Resistance mutations
      to RT inhibitors were studied by line probe assay (LiPA) or by automated
      sequencing in 468 patients (Madrid, 268; Galicia, 200), and resistance mutations
      to PR inhibitors were studied by automated sequencing in 295 patients (Madrid,
      85; Galicia, 210). RESULTS: The proportion of resistance mutations in treated and
      untreated patients results were higher by the LiPA method than by sequencing. By
      sequencing, we detected resistance mutations to nucleoside analogue RT (NRT)
      inhibitors and NRT inhibitors plus nonnucleoside RT (NNRT) inhibitors in 35.4%
      and 17.2% of treated patients, respectively. We also detected MDR to zidovudine
      plus lamivudine in 13.9% of treated patients from Galicia, in 1.7% from Madrid (p
      < 0.001), and in 1.5% of untreated patients from Galicia. Also, we detected MDR
      to NRT inhibitors in 3.8% and to NNRT inhibitors in 9.1%. We found resistance
      mutations to PR inhibitors in 38.1% of treated patients and in 0.9% of untreated
      patients. CONCLUSIONS: These findings reinforce the usefulness of testing for
      resistance mutations in some cases to evaluate their prevalence in a given
      population and in the follow-up of treated patients.

PMID- 10881997
TI  - Morphologic changes in human immunodeficiency virus type 1 virions secondary to
      intravirion reverse transcription: evidence indicating that reverse transcription
      may not take place within the intact viral core.
AB  - INTRODUCTION: In the past, retroviral endogenous reverse transcription (ERT) was
      considered an artificial process, secondary to permeabilization of the viral
      envelope by detergents or amphipathic peptides. However, recently we have
      demonstrated that ERT may occur in a variety of lentiviruses without detergent
      treatment and may lead to increased infectivity of lentivirions in initially
      quiescent T lymphocytes and nonproliferating cells, such as macrophages. As full
      length reverse transcripts could be synthesized within lentiviral particles, it
      is worth evaluating the potential alterations in lentiviral morphology due to the
      stimulation of intravirion reverse transcription. METHODS: Using quantitative DNA
      polymerase chain reaction (PCR) and transmission electron microscopy (TEM), we
      characterized critical alterations in human immunodeficiency virus type 1 (HIV-1)
      virions after stimulation of intravirion reverse transcription. RESULTS:
      Intravirion reverse transcription in HIV-1 virions was stimulated using
      deoxyribonucleoside triphosphates (dNTPs) and physiologic polyamines. Our studies
      indicated that HIV-1 virions, in which intravirion reverse transcription was
      stimulated, showed dissolution of the p24-shelled viral core and absence of the
      core-envelope linkage (CEL) region by TEM. These changes in the structure of the
      core correlate with the in vitro alterations in virion infectivity on primary
      cells. CONCLUSIONS: Stimulation of intravirion HIV-1 reverse transcription leads
      to morphologic changes in the viral particles that suggest changes in the compact
      viral core, which is consistent with active reverse transcription before
      infection of target cells. Further, via this unique approach, we suggest that
      intravirion or intracellular reverse transcription of HIV-1 is unlikely to take
      place within intact viral cores made up of p24-containing outer shells. As such,
      these results suggest a new approach to further dissect the intravirion or
      intracellular reverse transcription machinery of lentiviruses.

PMID- 10881996
TI  - Molecular evolution of human immunodeficiency virus type 1 subtype A in Senegal:
      1988-1997.
AB  - OBJECTIVE: Few studies have been able to track the genetic diversity of HIV-1
      viruses in human populations over time. We analyzed the molecular evolution of
      subtype A over a 10-year period, in a cohort of female sex workers with a known
      time of infection. STUDY DESIGN/METHODS: We amplified and sequenced the C2-V3
      region of the surface envelope glycoprotein from 73 HIV-1-infected women,
      infected between 1987-1997. RESULTS: Fifty-one patients were infected by subtype
      A viruses. The viruses demonstrated significant diversification (p < 0.001) with
      mean genetic distance increasing from 8.6% in 1989 to 15.9% in 1997. The slope of
      the fitted curve suggested a rate of diversification of 0.7% per year. The
      majority of subtype A viruses clustered with HIV-1 subtype A/G recombinant form
      (IbNG). CONCLUSION: The genetic diversity of HIV-1 subtype A infections doubled
      over the first 10 years of this high risk population's epidemic, suggesting that
      implementation of vaccines early in the epidemic may have a higher likelihood of
      success based on levels of genetic diversity. The A/G recombinant form (IbNG) has
      taken epidemic proportions in West Africa. This is of particular importance in
      understanding the epidemiology of HIV-1 subtypes in Africa and to further dissect
      the potential phenotypic and biological characteristics of these viruses.

PMID- 10881998
TI  - Bacterial diaminopimelate metabolism as a target for antibiotic design.

PMID- 10881999
TI  - 1-Substituted-4-[3-(1,2,3,4-tetrahydro-5- or 7-methoxynaphthalen-1
      yl)propyl]piperazines: influence of the N-1 piperazine substituent on 5-HT1A
      receptor affinity and selectivity versus D2 and alpha1 receptors. Part 6.
AB  - In the present paper, we report the synthesis and the binding profiles on 5-HT1A,
      D2, and alpha1 receptors of 1-substituted-4-[3-(5- or 7-methoxy-1,2,3,4
      tetrahydronaphthalen-1-yl)propyl]piperazine derivatives 19-32 and some related
      heteroalkyl derivatives 33-35. The results obtained are compared to those
      previously reported for the 1-phenyl, 1-(2-methoxyphenyl), 1-(2-pyridyl)
      analogues 2-9. The results pointed out the critical role of the group linked in
      the N-1 position of the piperazine in terms of 5-HT1A binding affinity. In fact,
      1-cyclohexyl, 1-(3-benzisoxazolyl), 1-(benzothiazole-2-carbonyl), 1-(2
      benzothiazolyl), 1-(2-quinolyl) substituted piperazines 21-30 displayed moderate
      or low 5-HT1A receptor affinity; on the contrary, 1-(3-benzisothiazolyl) and 1-(1
      naphthalenyl) substituted piperazines 19, 20 and 32 displayed high 5-HT1A
      receptor affinity, the Ki values being in the subnanomolar range. Furthermore,
      compounds 19, 20 and 32 demonstrated better selectivity over alpha1 receptors
      than the reference compounds 2-9.

PMID- 10882000
TI  - Structure-activity relationship at alpha-adrenergic receptors within a series of
      imidazoline analogues of cirazoline.
AB  - Several analogues of cirazoline (2), a selective alpha1-adrenoreceptor agonist,
      were prepared and their pharmacological profiles studied. Although at the alpha1
      adrenoreceptor all the compounds displayed a significant agonist activity, at the
      alpha2-adrenoreceptor they showed either agonist or antagonist activity depending
      on the nature of the phenyl substituent. The qualitative structure-activity
      relationship led us to the conclusion that the oxygen atom in the side-chain is
      essential for alpha1-agonist activity, while the cyclopropyl ring is not, and may
      be replaced by several groups. Of the groups studied, isopropoxy appears to be
      the best. Instead, the same substitution (i.e., isopropoxy for the cyclopropyl
      ring) at alpha2-adrenoreceptors causes a reversal of activity. On the other hand,
      the cyclopropyl ring seems to be important for alpha1-selectivity. Compound 20 is
      the most potent alpha1-agonist of the series, being equiactive with cirazoline on
      rat vas deferens and in pithed rat.

PMID- 10882001
TI  - Preparation of dopaminergic N-alkyl-benzyltetrahydroisoquinolines using a 'one
      pot' procedure in acid medium.
AB  - The preparation of N-methyl-BTHIQ (4) from N-phenylethyl-phenacetamide (1) by
      cyclization, reduction and N-alkylation in acid medium has been achieved in good
      yield in a 'one-pot' procedure. Acylation of imine (2) intermediate afforded the
      Z and E stereoselectivity in the enamide formation. 6-Hydroxy-BTHIQ (7) shows
      selectivity for D2 dopamine receptors, while its N-methylated homologue (8)
      displays higher affinities for both D1 and D2 receptor types, with an unexpected
      increase in D1 dopamine receptor affinity.

PMID- 10882002
TI  - Cyclobutane carboxamide inhibitors of fungal melanin: biosynthesis and their
      evaluation as fungicides.
AB  - A new fungicide lead has been identified by enzyme screening of a focused
      combinatorial library. The lead compound 4, a potent inhibitor of scytalone
      dehydratase (SD), exhibits fungicidal activity upon foliar application but does
      not show systemic activity. The X-ray crystal structure of the enzyme-inhibitor
      complex and an appreciation for the relationship between physical properties and
      systemic activity enabled us to rapidly improve upon this initial lead. The
      geminal halogen-methyl group combination was found to be optimal for interaction
      with the bounding serine and asparagine side-chain residues. Replacement of CF3
      with methyl was a key discovery, giving inhibitors with slightly diminished
      enzyme inhibition potency while significantly increasing systemic activity.
      Amides prepared from amines with 2,4-dichloro substitution on the phenyl ring
      gave the most potent enzyme inhibitors. Two compounds from this series showed
      systemic activity comparable to the commercial standard and were selected for
      outdoor testing in flooded plots which simulate rice paddies.

PMID- 10882003
TI  - Ionization behaviour and tautomerism-dependent lipophilicity of pyridine-2(1H)
      one cardiotonic agents.
AB  - The acid-base properties of pyridine-2(1H)-one derivatives, analogues of the
      cardiotonic agent milrinone, were studied by capillary zone electrophoresis
      (CZE). Electrophoretic mobility and pH data were fitted to equilibrium
      expressions and apparent dissociation constants (pKa) calculated by non-linear
      regression. Compared with the ultraviolet (UV) spectrophotometric method and
      potentiometric titrations, the CZE technique showed advantages, such as rapidity
      and applicability to compounds that are sparingly soluble in water. Based on the
      pKa values, intramolecular electronic interactions were assessed. The
      lipophilicity of a number of derivatives was also examined, by determining their
      n-octanol/water distribution coefficients over a wide pH range, and found to be
      significantly affected by 2-pyridone/2-hydroxypyridine tautomerism. As revealed
      by a comparison between experimental and calculated log P values, electron
      withdrawing substituents, especially at the C(6) position of 2-pyridone, favour
      the less polar hydroxypyridine tautomers both in water and octanol. Our results
      indicate that the positive inotropism of milrinone-related compounds could be
      explained taking ionization and tautomerism into account.

PMID- 10882004
TI  - A new affinity ligand for the isolation of a single 'feruloyl esterase' (FAE-III)
      from Aspergillus niger.
AB  - 8-Aminooctyl 5'-S-coniferyl-5'-deoxy-thio-alpha-L-arabinofuranoside has been
      synthesised and shown to be a selective affinity ligand for the feruloyl esterase
      III of Aspergillus niger. The hydrolyses of methyl 5-O-coumaroyl, feruloyl, or
      sinapoyl alpha-L-arabinofuranosides by this enzyme proceed at comparable rates.

PMID- 10882005
TI  - Sterol C-methyl transferase from Prototheca wickerhamii mechanism, sterol
      specificity and inhibition.
AB  - The membrane-bound sterol methyl transferase (SMT) enzyme from Prototheca
      wickerhamii, a non-photosynthetic, yeast-like alga, was found to C-methylate
      appropriate delta24(25)-sterol acceptor molecules to delta25(27)-24beta-methyl
      products stereoselectively. Incubation with pairs of substrates--[2H3
      methyl]AdoMet and cycloartenol, and AdoMet and [27-(13)C]lanosterol--followed by
      1H and 13C NMR analysis of the isotopically labeled products demonstrated the si
      face (beta-face attack) mechanism of C-methylation and the regiospecificity of
      delta25(27)-double bond formation from the pro-Z methyl group (C27) on
      lanosterol. The enzyme has a substrate preference for a sterol with a 3beta
      hydroxyl group, a planar nucleus and a side chain oriented into a 'right-handed'
      structure (20R-chirality) characteristic of the native substrate, cycloartenol.
      The apparent native molecular weight of the SMT was determined to be
      approximately 154,000, as measured by Superose 6 FPLC. A series of sterol
      analogues which contain heteroatoms substituted for C24 and C25 or related
      structural modifications, including steroidal alkaloids, havs been used to probe
      further the active site and mechanism of action of the SMT enzyme. Sterol side
      chains containing isoelectronic modifications of a positively charged moiety in
      the form of an ammonium group substituted for carbon at C25, C24, C23 or C22 are
      particularly potent non-competitive inhibitors (Ki for the most potent inhibitor
      tested, 25-azacycloartanol, was ca. 2 nM, four orders of magnitude less than the
      Km for cycloartenol of 28 microM), supporting the intermediacy of the 24-methyl
      C24(25)-carbenium ion intermediate. Ergosterol, but neither cholesterol nor
      sitosterol, was found to inhibit SMT activity (Ki = 80 microM). The combination
      of results suggests that the interrelationships of substrate functional groups
      within the active center of a delta24(25) to delta25(27) 24beta-methyl-SMT could
      be approximated thereby allowing the rational design of C-methylation inhibitors
      to be formulated and tested.

PMID- 10882006
TI  - Sequence-selectivity of 5,11-dimethyl-5H-indolo[2,3-b]quinoline binding to DNA.
      Footprinting and molecular modeling studies.
AB  - Indolo[2,3-b]quinolines are a new family of the DNA intercalators showing
      significant cytotoxic activity. The mechanism of their action is based on the
      inhibition of DNA topoisomerase II activity. It depends on their ability to
      induce and stabilize drug-topII-DNA cleavable complexes. Site-specific
      intercalation of 5,11-dimethyl-5H-indolo[2,3-b]quinoline (DiMIQ) was analyzed in
      vitro by DNaseI footprinting and by molecular modeling. To model the DNA
      intercalator complex, use was made of the CVFF and ESFF force fields implemented
      in Insight 97.0 software. Experimental results were verified using a simple
      statistical model. The DiMIQ molecule was found to bind preferentially to the
      pBR322 DNA plasmid in the 5'-TGCTAACGC-3' region between adjacent adenine bases.

PMID- 10882007
TI  - New aromatase inhibitors. Synthesis and biological activity of aryl-substituted
      pyrrolizine and indolizine derivatives.
AB  - We report herein the design and the synthesis of some aryl-substituted
      pyrrolizine and indolizine derivatives, on the basis of a hypothetical
      pharmacophore structure designed to fit the catalytic site of the human
      cytochrome P450 aromatase. The in vitro biological evaluation of these compounds
      allowed us to point out two new potent non-steroidal aromatase inhibitors, MR
      20494 and MR 20492, with IC50 values in the range of 0.1 microM.

PMID- 10882008
TI  - 2H-Thieno[3,2-e]- and [2,3-e]-1,2-thiazine-6-sulfonamide 1,1-dioxides as ocular
      hypotensive agents: synthesis, carbonic anhydrase inhibition and evaluation in
      the rabbit.
AB  - Novel non-chiral 2H-thieno[3,2-e]- and [2,3-e]-1,2-thiazine-6-sulfonamide 1,1
      dioxides were synthesized for evaluation as potential candidates for the
      treatment of glaucoma. All of the compounds prepared were potent high affinity
      inhibitors of human carbonic anhydrase II, Ki < 0.5 nM. Additionally, inhibition
      of recombinant human carbonic anhydrase IV was determined for selected compounds;
      these were shown to be moderate to potent inhibitors of this isozyme with IC50
      values ranging from 4.25 to 73.6 nM. Of the compounds evaluated for their ability
      to lower intraocular pressure in naturally hypertensive Dutch-belted rabbits, 5a,
      17a3, 17b1, 17b2, 17h2 and 17i1 showed significant efficacy (> 20% decrease) in
      this model following topical ocular administration.

PMID- 10882009
TI  - Synthesis and antitumor activity of some indeno[1,2-b]quinoline-based bis
      carboxamides.
AB  - A series of bis(11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides) linked through
      the 6-carboxamides were prepared by coupling the requisite acid imidazolides with
      various diamines. Compounds with mono-cationic linker chains were more potent
      cytotoxins than the corresponding monomer in a panel of rodent and human cell
      lines, while those with the dicationic linker chains (CH2)2NR(CH2)2NR(CH2)2 and
      (CH2)2NR(CH2)3NR(CH2)2 showed extraordinarily high potencies (for example, IC50s
      of 0.18-1.4 nM against human Jurkat leukemia; up to 1000-fold more potent than
      the parent monomer). As seen previously in the monomeric series, small,
      lipophilic 4-substituents significantly increased potency in cell culture. The
      dimeric compounds were all slightly to significantly more potent in the mutant
      JL(A) and JL(D) cell lines that under-express topo II, suggesting that this
      enzyme is not their primary target. An 11-imino-linked dimer was much less
      active, and an asymmetric indeno[1,2-b]quinoline-6-carboxamide/naphthalimide
      dimer was less active than the comparable symmetric bis(indeno[1,2-b]quinoline-6
      carboxamide). Selected analogues were active against sub-cutaneously implanted
      colon 38 tumors in mice, giving growth delays comparable to that of the clinical
      topo I inhibitor irinotecan at up to 10-fold lower doses. These compounds form an
      interesting new class of putative topo I inhibitors.

PMID- 10882010
TI  - Synthesis and evaluation of oligo-1,3-thiazolecarboxamide derivatives as HIV-1
      reverse transcriptase inhibitors.
AB  - A set of oligo-1,3-thiazolecarboxamide derivatives able to interact with the
      minor groove of nucleic acids was synthesized. These oligopeptides contained
      different numbers of thiazole units presenting dimethylaminopropyl or EDTA
      moieties on the C-terminus, and aminohexanoyl or EDTA moieties on the N-terminus.
      The inhibition of such compounds on HIV-1 reverse transcriptase activity was
      evaluated using different model template primer duplexes: DNA x DNA, RNA x DNA,
      DNA x RNA and RNA x RNA. The biological properties of the thiazolecarboxamide
      derivatives were compared to those of distamycin, another minor groove binder
      which contains three pyrrole rings. Similar to distamycin, the thiazole
      containing oligopeptides were good inhibitors of the reverse transcription
      reaction in the presence of DNA x DNA. But in contrast to distamycin, the
      oligothiazolide derivatives were able to inhibit reverse transcription in the
      presence of RNA x DNA or DNA x RNA template primers. Both distamycin and
      oligothiazolecarboxamides had low affinity for RNA x RNA duplexes. The inhibition
      obtained with the newly synthesized thiazolecarboxamides showed that these
      compounds were more powerful and versatile inhibitors of the RT-dependent
      polymerization than the natural minor groove binder distamycin.

PMID- 10882011
TI  - A class of 4-aza-lithocholic acid-derived haptens for the generation of catalytic
      antibodies with steroid synthase capabilities.
AB  - The syntheses of a class of three haptens derived from the same 4-aza-steroidal
      skeleton is described. The sequence begins with oxidative cleavage of ring A of
      commercially available, optically pure lithocholic acid. Insertion of nitrogen at
      position 4 and stereoselective hydrogenation of the resulting electron-rich
      enelactam under 600 psi H2 yielded a system analogous to testosterone-5-alpha
      reductase inhibitors. Upon exhaustive reduction of this compound with lithium
      aluminium hydride, a linker for bioconjugation was attached before the N-oxide
      key functionality is established in ring A. This functional group is believed to
      be a true transition-state mimic for the electronic nature of initiation of the
      cationic cyclization of 2,3-epoxy-squalene derivatives. In addition, it also
      holds promise for eliciting acidic residues as part of a bait-and-switch
      strategy. Remarkably, both N-oxide epimers obtained from mCPBA oxidation can be
      separated by column chromatography on a 60 mg scale and were used in enantiopure
      form for separate immunizations. Reliable configurative assignment was carried
      out by comparison studies with previously characterized and published systems. A
      catalytic antibody (HA8-25A10) was obtained from the immunization with the hapten
      bearing an aminoxide oxygen in the beta position. Surprisingly, an inhibition
      study showed that the isomer with the inverted configuration at the N-oxide bound
      more strongly to this catalytic antibody.

PMID- 10882012
TI  - Utilization of the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold in the design
      of potent inhibitors of serine proteases: SAR studies using carboxylates.
AB  - A series of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1
      dioxide and isothiazolidin-3-one 1,1 dioxide scaffolds has been synthesized and
      the inhibitory profile of these compounds toward human leukocyte elastase (HLE),
      cathepsin G (Cat G) and proteinase 3 (PR 3) was then determined. Most of the
      compounds were found to be potent, time-dependent inhibitors of elastase, with
      some of the compounds exhibiting k(inact)/K1 values as high as 4,928,300 M(-1) s(
      1). The inhibitory potency of carboxylate derivatives based on the 1,2,5
      thiadiazolidin-3-one 1,1 dioxide platform was found to be influenced by both the
      pKa and the inherent structure of the leaving group. Proper selection of the
      primary specificity group (R(I)) was found to lead to selective inhibition of HLE
      over Cat G, however, those compounds that inhibited HLE also inhibited PR 3,
      albeit less efficiently. The predictable mode of binding of these compounds
      suggests that, among closely-related serine proteases, highly selective
      inhibitors of a particular serine protease can be fashioned by exploiting subtle
      differences in their S' subsites. This study has also demonstrated that the
      degradative action of elastase on elastin can be abrogated in the presence of
      inhibitor 17.

PMID- 10882013
TI  - Chemoenzymatic synthesis of PSGL-1 glycopeptides: sulfation on tyrosine affects
      glycosyltransferase-catalyzed synthesis of the O-glycan.
AB  - PSGL-1 is the primary glycoprotein ligand for P-selectin during the inflammatory
      response. Interestingly, the N-terminal sequence, containing both a site of
      tyrosine sulfation and an O-glycan, has been shown to bind to P-selectin with an
      affinity similar to full-length PSGL-1. To further characterize this system, the
      synthesis of glycopeptides from PSGL-1 was undertaken. The synthesis involved
      both solution- and solid-phase synthesis, as well as enzymatic transformations.
      During the synthesis, notable reactivity differences of the glycosyltransferases
      toward sulfated and unsulfated versions of the same glycopeptides were observed.

PMID- 10882014
TI  - New antineoplastic prenylhydroquinones. Synthesis and evaluation.
AB  - Several prenylhydroquinones have been prepared through Diels-Alder condensation,
      further functionalized or degraded chemically and then evaluated for their
      cytotoxic activity against some neoplastic cultured cell lines. A number of them
      have shown IC50 values under the microM level.

PMID- 10882015
TI  - Synthesis and antitumor activity of selected 7-alkylidene substituted cephems.
AB  - Selected 7-alkylidene substituted cephems were synthesized and subjected to
      antitumor assay. The effect of substituents was examined to establish structure
      activity relationships. It was found that the intensive intracellular generation
      of nitric oxide induced by tert-butyl 7-alkylidene cephalosporanate sulfones
      could be also regarded as an additional cytotoxic factor taking place both in
      vitro and in vivo experiments.

PMID- 10882016
TI  - New carbamoylpiperidines as human platelet aggregation inhibitors.
AB  - A series of 3-carbamoylpiperidines (nipecotamides) are designed, synthesized and
      tested for their inhibitory action against adenosine diphosphate (ADP)-induced
      aggregation of human platelets. A structure-activity analysis of the
      bis(nipecotamido)aralkane type showed that a substituent on the piperidine ring
      should preferably be an amide and that the electronegativity of the carbonyl
      oxygen and the orientation of the amide group affected activities. Based on the
      knowledge of factors influencing platelet activation and aggregation, a nitric
      ester moiety which could release nitric oxide (NO) in situ, is incorporated into
      the nipecotamide structure. These compounds exhibit increased activity compared
      to those having no -ONO2 function. They also show stereoselectivity, with the
      meso isomer being approximately twice as potent as the synthetic diastereomeric
      mixture. Replacement of the -ONO2 function with hydroxyl, ester or alkyl groups
      considerably diminishes aggregation-inhibitory potential. Nipecotamides are shown
      here to inhibit the basal and collagen-induced rise in platelet inositol
      trisphosphate (IP3) levels, as well as phosphoinositide turnover. A comprehensive
      mechanism of action is proposed taking earlier results into consideration.

PMID- 10882017
TI  - Brain-targeted chemical delivery of [Leu2, Pip3]-TRH: synthesis and biological
      evaluation.
AB  - A chemical targeting system for [Leu2, Pip3]-TRH (Gln,Leu,Pip) was synthesized in
      order to allow its specific delivery to the central nervous system (CNS).
      Sequential metabolism of the obtained 'packaged' chemical delivery system, (CDS),
      DHT-Pro-Pro-Gln-Leu-Pip-OCh, should yield a 'locked-in' precursor following the
      oxidative conversion of the dihydrotrigonellyl (DHT) to the trigonellyl (T+)
      moiety, followed by removal of the cholesteryl function and cleavage of the T+
      Pro-Pro by prolyl endopeptidase. The antagonism of barbiturate-induced sleeping
      time was used to assess the activity of the CDS. The sleeping time after
      administration of vehicle and [Leu2]-TRH was 100.5 +/- 6.3 min, and 78.2 +/- 4.7
      min, respectively. The [Leu2, Pip3]-TRH-CDS showed a significant decrease in
      sleeping time (58.2 +/- 3.4 min) compared to the vehicle or [Leu2]-TRH. These
      results indicate successful brain delivery of the precursor construct, and an
      effective release of the active GlnLeuPip in the brain.

PMID- 10882018
TI  - Synthesis, hydroxyl radical production and cytotoxicity of analogues of
      bleomycin.
AB  - Two pyridine analogues of the metal complexing region of the anticancer drug
      bleomycin and two related but deactivated prodrugs have been linked to a 2,6
      diphenylpyridine derivative as a DNA binding unit. The 2,6-diphenylpyridine
      system is structurally related to known amplifiers of the cytotoxicity of
      bleomycin. The conjugates were found to bind to DNA more strongly than bleomycin
      A2 and were more cytotoxic than the corresponding compounds lacking the DNA
      binding unit. On exposure of a mixture of cells and prodrugs to hypoxia and then
      air, the prodrug containing the nitrohistidine unit was not bioreductively
      activated but the prodrug having an N-oxide group was bioreductively activated.
      This result represents a novel approach to the improvement of the therapeutic
      ratio of bleomycin analogues.

PMID- 10882019
TI  - Conformationally restricted analogues designed for selective inhibition of GAR
      Tfase versus thymidylate synthase or dihydrofolate reductase.
AB  - The synthesis and evaluation of a series of conformationally restricted analogues
      of 10-formyl-tetrahydrofolate as potential inhibitors of glycinamide
      ribonucleotide transformylase (GAR Tfase) or aminoimidazole carboxamide
      transformylase (AICAR Tfase) are reported.

PMID- 10882020
TI  - Biaryl diacid inhibitors of human s-PLA2 with anti-inflammatory activity.
AB  - Twenty-four hydrophobic dicarboxylic acids are described which were evaluated as
      inhibitors of 14 kDa human platelet phospholipase A2 (HP-PLA2). In general,
      biarylacetic acid derivatives were found to be more active than biaryl acids or
      biarylpropanoic acids. More potent inhibitors were obtained when hydrophobic
      groups were attached to the biaryl acid nucleus using an olefin linkage as
      compared to an ether linkage. Compounds with larger hydrophobic groups were
      usually more potent inhibitors of HP-PLA2. Five of the compounds disclosed in
      this report (2, 4, 28, 36b and 36i) were found to possess significant anti
      inflammatory activity in a phorbol ester induced mouse ear edema model of chronic
      inflammation.

PMID- 10882021
TI  - Synthesis and antimalarial activities of base-catalyzed adducts of 11
      azaartemisinin.
AB  - A series of N-substituted 11-azaartemisinins were prepared in high yield
      employing base-catalyzed additions to an amide nitrogen of olefins and terminal
      acetylenes conjugated with electron withdrawing groups (EWGs). When the terminal
      acetylene was conjugated with carbomethoxy, N,N-dimethyl amide or carbonyl
      groups, the E-adducts resulted. A mixture of E- and Z-adducts were obtained when
      the EWG was a nitrile. In vitro antimalarial activities of each compound were
      determined against two drug-resistant strains of Plasmodium falciparum. Many of
      the compounds prepared were several times more active than artemisinin.

PMID- 10882022
TI  - Interaction of pyrimethamine, cycloguanil, WR99210 and their analogues with
      Plasmodium falciparum dihydrofolate reductase: structural basis of antifolate
      resistance.
AB  - The nature of the interactions between Plasmodium falciparum dihydrofolate
      reductase (pfDHFR) and antimalarial antifolates, i.e., pyrimethamine (Pyr),
      cycloguanil (Cyc) and WR99210 including some of their analogues, was investigated
      by molecular modeling in conjunction with the determination of the inhibition
      constants (Ki). A three-dimensional structural model of pfDHFR was constructed
      using multiple sequence alignment and homology modeling procedures, followed by
      extensive molecular dynamics calculations. Mutations at amino acid residues 16
      and 108 known to be associated with antifolate resistance were introduced into
      the structure, and the interactions of the inhibitors with the enzymes were
      assessed by docking and molecular dynamics for both wild-type and mutant DHFRs.
      The Ki values of a number of analogues tested support the validity of the model.
      A 'steric constraint' hypothesis is proposed to explain the structural basis of
      the antifolate resistance.

PMID- 10882023
TI  - Microbial transformation of 2-hydroxy and 2-acetoxy ketones with Geotrichum sp.
AB  - Biotransformation of a series of o-, m- and p-substituted alpha-hydroxy- and
      alpha-acetoxyphenylethanones 1a-h and 9a-g with Geotrichum sp. led to the
      corresponding 1,2-diols 2 and/or monoacetates 10 in moderate to excellent
      enantiomeric excesses. Alpha-hydroxy- and alpha-acetoxyphenylethanones and their
      m- and p-derivatives gave preponderantly the S-configuration products while in
      the case of the o-derivatives R-alcohol was provided as the major enantiomer. The
      results of stereoselectivity were discussed.

PMID- 10882024
TI  - (Partial) agonist/antagonist properties of novel diarylalkyl carbamates on
      histamine H3 receptors.
AB  - In the search for new ligands of the histamine H3 receptor, novel diarylalkyl
      carbamates (1-19) were synthesized as derivatives of 3-(1H-imidazol-4-yl)propanol
      and -ethanol. Carbamates were built up via isocyanates either from corresponding
      amines by reaction with diphosgene or from related carboxylic
      acid/diphenylphosphoryl azide and the alcoholic component. Sterically hindered
      amines were prepared in a two-step reaction sequence from corresponding ketones.
      Some of the title compounds showed (partial) agonist activity at the histamine H3
      receptor in vitro and in vivo. Diphenylmethyl carbamate 2 was identified as a new
      lead structure (ED50 = 5.3 +/- 2.6 mg/kg po, alpha = 1.0). Aromatic substitution
      in ortho- or para-positions of 2 led to a loss of agonist activity. meta
      Substitution was tolerated to some extent. These effects seemed to be caused by
      steric rather than electronic properties of the substituents. An investigation of
      exchange of one or both phenyl rings of 2 by heterocyclic rings led to the highly
      active and selective thienyl derivative 18 (ED50 3.4 +/- 1.4 mg/kg p.o., alpha =
      1.0). These new (partial) agonists of the histamine H3 receptor might serve as
      pharmacological tools for investigating molecular aspects of the H3 receptor or
      as possible centrally acting therapeutic agents with oral bioavailability.

PMID- 10882025
TI  - Structural bases for the inhibition of aldose reductase by phenolic compounds.
AB  - Aldose reductase (ALR2) is an enzyme involved in the development of long-term
      diabetic complications. In the search for aldose reductase inhibitors less acidic
      than carboxylic acids, phenolic compounds related to benzopyran-4-one and
      chalcone are particularly interesting because they possess good inhibitory
      properties. In order to investigate the similarities between these two classes of
      compounds and to provide a structural basis for their inhibition of ALR2, the
      existing structure-activity relationships were reconsidered. To this end, the
      acidity constants of a set of chalcones were measured and compared with those of
      benzopyran-4-one derivatives. Then, having established the relevant protonation
      state of these phenolics at physiological pH, a conformational analysis was
      performed on the most active benzopyran-4-one and chalcone derivatives and the
      results were compared with the crystal structures of some analogues. Finally,
      molecular docking of the most active chalcone into the ALR2 binding site was
      performed, and the structure of the enzyme-inhibitor complex was compared with
      that of the complex formed between ALR2 and a previously-obtained benzopyran-4
      one derivative.

PMID- 10882026
TI  - Orally active cephalosporins. Part 2: synthesis, structure-activity relationships
      and oral absorption of cephalosporins having a C-3 pyridyl side chain.
AB  - A series of 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamid
      o]cephalosporins having a pyridine ring connected through various spacer moieties
      at the C-3 position was designed and synthesized and evaluated for antibacterial
      activity and oral absorption in rats. All compounds showed potent antibacterial
      activity against Staphylococcus aureus, whereas antibacterial activity against
      gram-negative bacteria was markedly influenced by the spacer moiety between the
      pyridine and cephem nucleus. Oral absorption was influenced by the position of
      the pyridine nitrogen as well as by the spacer moiety. Among these compounds,
      FR86830 (14), having a 4-pyridylmethylthio moiety at the C-3 position, showed the
      most well balanced activity and moderate oral absorption.

PMID- 10882027
TI  - Substituted benz[a]acridines and benz[c]acridines as mammalian topoisomerase
      poisons.
AB  - Coralyne and several other synthetic benzo[a,g]quinolizium derivatives related to
      protoberberine alkaloids have exhibited activity as topoisomerase poisons. These
      compounds are characterized by the presence of a positively charged iminium
      group, which has been postulated to be associated with their pharmacological
      properties. The objective of the present study was to devise stable noncharged
      bioisosteres of these compounds. Several similarly substituted benz[a]acridine
      and benz[c]acridine derivatives were synthesized and their relative activity as
      topoisomerase poisons was determined. While the benz[c]acridine derivatives
      evaluated as part of this study were devoid of topoisomerase poisoning activity,
      several dihydrobenz[a]acridines were able to enhance DNA cleavage in the presence
      of topo I. In contrast to certain protoberberine derivatives that did exhibit
      activity as topo II poisons, none of the benz[a]acridines derivatives enhanced
      DNA cleavage in the presence of topo II. Among the benz[a]acridines studied, 5,6
      dihydro-3,4-methylenedioxy-9,10-dimethoxybenz[a]acridine, 13e, was the most
      potent topo I poison, with comparable potency to coralyne. These data suggest
      that heterocyclic compounds structurally related to coralyne can exhibit potent
      topo I poisoning activity despite the absence of an iminium cation within their
      structure. In comparison to coralyne or other protoberberine derivatives, these
      benz[a]acridine derivatives possess distinctly different physicochemical
      properties and represent a novel series of topo I poisons.

PMID- 10882028
TI  - Design, synthesis and structure-affinity relationships of 4-methylidenepiperidine
      and 4-aryl-1,2,3,6-tetrahydropyridine derivatives as corticotropin-releasing
      factor1 receptor antagonists.
AB  - Recently, various non-peptide corticotropin-releasing factor1 (CRF1) receptor
      antagonists have been reported. Structure-affinity relationships (SARs) of non
      peptide CRF antagonists suggest that such antagonists can be constructed of three
      units: a hydrophobic unit (Up-Area), a proton accepting unit (Central-Area), and
      an aromatic unit (Down-Area). Our interest focused on the Up-Area in deriving the
      novel methylidenepiperidine derivatives 8-10 and 4-aryl-1,2,3,6
      tetrahydropyridine derivatives 11-13 as non-peptide CRF1 receptor antagonists.
      Compounds 8a and 11a had moderate affinity for CRF1 receptor, but compounds 9,
      10, 12 and 13 did not exhibit CRF1 receptor affinity. Modification of derivatives
      11 afforded compounds 11i (CRA1001) and 11x (CRA1000), which had high affinity
      and selectivity for CRF1 receptors with potent anxiolytic-like and antidepressant
      like properties in some experimental animal models. These findings suggest that
      the hydrophonic unit (Up-Area) may be useful for design of CRF1 antagonists. We
      report here the design, synthesis and SARs of the derivatives 8 and 11 and
      isosteres 9, 10, 12 and 13.

PMID- 10882029
TI  - Synthesis and antitumor activity of duocarmycin derivatives: modification at the
      C-7 position of segment-A of A-ring pyrrole compounds.
AB  - A series of the C7-substituted A-ring pyrrole derivatives of duocarmycin were
      synthesized, and evaluated for in vitro anticellular activity against HeLa S3
      cells and in vivo antitumor activity against murine sarcoma 180 in mice. All of
      the C7-substituted A-ring pyrrole compounds decreased potency in vitro and in
      vivo. However, some showed strong antitumor activity with T/C values less than
      0.3. Among them, the 7-formyl compound 5d showed remarkable potent in vivo
      antitumor activity and low peripheral blood toxicity, which were equal to 2c.

PMID- 10882030
TI  - Effects of short-acting NMDA receptor antagonist MRZ 2/576 on morphine tolerance
      development in mice.
AB  - The present study sought to evaluate the ability of a short-acting glycineB site
      NMDA receptor antagonist, MRZ 2/576, to affect morphine tolerance development in
      mice. It was found that MRZ 2/576 (10 mg/kg, i.p.) significantly retarded
      development of morphine analgesic tolerance (20 mg/kg, s.c., 8 days, once a day;
      tail-flick test) when administered 120 min or 150 min after each daily morphine
      injection. MRZ 2/576 did not affect the development of morphine tolerance when
      administered immediately, 15, 30, 60, 90, 180, 240, 300 or 360 min after the
      daily morphine injections. Thus, short-acting NMDA receptor antagonists may be
      useful in exploring the temporal characteristics of opioid tolerance (i.e.,
      periods after morphine injection that are critical for tolerance induction) and
      the present study suggests that after morphine administration there is a period
      of NMDA receptors activation crucial for the development of tolerance.

PMID- 10882031
TI  - Pharmacodynamic interaction between mibefradil and other calcium channel
      blockers.
AB  - Briefly after withdrawal of the (T-type) calcium channel blocker mibefradil from
      the market, four cases of life-threatening interaction of mibefradil with
      dihydropyridines were reported. We investigated in vitro whether mibefradil
      interacts with a dihydropyridine, as described for other non-dihydropyridine
      compounds. Rat working hearts were used to examine functional interactions
      between amlodipine and mibefradil. Gallopamil and another T-type-channel blocker,
      ethosuximide, were included for comparison. Effects of mibefradil, (+)- and (-)
      gallopamil on [3H](+)-isradipine binding were studied in membranes from tsA201
      cells transfected with alpha(1c)-, alpha(2)delta-, and beta(1a)- or beta(2a)
      calcium channel subunits. Mibefradil increased negative inotropic effect of
      amlodipine, but not of gallopamil. Gallopamil and ethosuximide showed no
      influence on contractile effects of amlodipine. Furthermore, mibefradil
      concentration-dependently caused bradycardic rhythm disturbance. The same type of
      arrhythmia was observed combining low concentrations of mibefradil with
      amlodipine, or with gallopamil, respectively. Amlodipine alone, or the
      combination of gallopamil or ethosuximide with amlodipine did not cause any
      arrhythmia. Binding studies showed a concentration-dependent positive allosteric
      interaction between [3H](+)-isradipine and mibefradil, but not with [3H](+)
      isradipine and gallopamil enantiomers. Molecular and functional evidence points
      to an interaction between a dihydropyridine and mibefradil. Mibefradil caused
      rhythm disturbances and potentiation of negative inotropy when combined with
      amlodipine.

PMID- 10882032
TI  - Morphine self-administration in mu-opioid receptor-deficient mice.
AB  - Morphine-induced place preference was demonstrated recently in wild-type mice,
      whereas this conditioned behaviour was not observed in mu-opioid receptor
      deficient mice. In the present study, we investigated locomotor effects of
      subcutaneously (s.c.) injected morphine as well as intracerebroventricular
      (i.c.v.) morphine self-administration in mu-opioid receptor-knockout mice. After
      s.c. morphine injection, locomotor activity significantly increased in wild-type
      animals. As expected, in the self-administration test the rate of self
      administration constantly increased in wild-type mice reflecting reward effects
      of morphine. This increase was independent of locomotor/motor activity. In
      contrast, self-administration rates and locomotor/motor activity significantly
      decreased in the receptor-deficient animals. It was shown that this aversive
      effect might partly be due to kappa-opioid receptor interaction.

PMID- 10882033
TI  - Pharmacological properties of Ca(V)3.2, a low voltage-activated Ca2+ channel
      cloned from human heart.
AB  - Three genes encoding T-type Ca2+ channels have been described but their
      correspondence to the various native T-type Ca2+ currents remains uncertain. In
      particular, Ca(V)3.2 (or alpha1H) was cloned from a human heart library, its
      message was found abundantly in cardiac tissue, and expressed Ca(V)3.2 was shown
      to conduct low voltage-activated currents, which inactivate rapidly and are
      sensitive to Ni2+ and mibefradil. These observations suggested that Ca(V)3.2
      might encode native cardiac T-type Ca2+ channels but more information on the
      pharmacology of Ca(V)3.2 was needed to confirm this hypothesis. In the present
      study, we compare the pharmacology of Ca(V)3.2 expressed in HEK293 cells and of
      native T-type Ca2+ channels in guinea pig atrial myocytes ("native-T"). (1)
      Ca(V)3.2 and native-T are insensitive to TTX and to toxins selective for N-, P-,
      or Q-type Ca2+ channels (omega-CTx-GVIA, omega-Aga-IVA, omega-CTx-MVIIC). (2) The
      half-maximal blocking concentration (IC50) of mibefradil on Ca(V)3.2 is near that
      on native-T and the block is similarly voltage-dependent. (3) Ca(V)3.2 is five-
      to sixfold less sensitive than native-T to the 1,4-dihydropyridine (DHP)
      amlodipine, suggesting a difference in the DHP binding site. (4) Both channels
      display similar (but not identical) sensitivities to the inorganic blockers Ni2+
      and Cd2+ and the IC50s are in the range of values found for T-type Ca2+ currents
      in other cell types. (5) Ni2+ shifts the voltage dependence of Ca(V)3.2
      activation but not that of native-T. The many similarities between the two
      channels support the contention that Ca(V)3.2 encodes cardiac T-type Ca2+
      channels. The slight differences may be due to species variations and/or to the
      choice of splice variant.

PMID- 10882034
TI  - Effects of physical training on functional activity of 5-HT1B receptors in rat
      central nervous system: role of 5-HT-moduline.
AB  - The effect of physical exercise was examined on the sensitivity of 5-HT1B
      receptors and on 5-HT-moduline tissue concentration in the central nervous system
      of rats. Rats were trained for 7 consecutive weeks to run on a treadmill. Three
      groups of animals were selected: group 1, sedentary rats (controls); group 2,
      animals running for 1 h at 18 m/min for 5 days per week (moderate training) and
      group 3, animals running for 2 h, at 30 m/min on a 7% grade for 5 days per week
      (intensive training). The animals were sacrificed 24 h after the last running.
      Rat brains were dissected out to obtain hippocampus and substantia nigra and kept
      at -80 degrees C until use. 5-HT1B receptor activity was determined by studying
      [35S]GTPgammaS binding in a substantia nigra membrane preparation from individual
      animals, after stimulation by a selective 5-HT1B receptor agonist (CP 93,129). 5
      HT-moduline tissue content in hippocampus from individual animals was determined
      by ELISA using a polyclonal anti-5-HT-moduline antibody. In moderately trained
      animals (n=5), the CP 93,129-stimulated [35S]GTPgammaS binding curve was shifted
      to the right compared with controls (n=6), whereas the binding was totally
      suppressed in intensely trained animals (n=5). In parallel, 5-HT-moduline tissue
      concentration in the hippocampus was slightly increased in moderately trained
      animals (117.3 +/- 8.9%) (n=5), whereas it was significantly increased in
      intensely trained animals (182.6 +/- 29.5%) (n=5) compared to controls (100 +/-
      6.11%) (n=6). These results show that 5-HT1B receptors are slightly desensitized
      in moderately trained animals and totally desensitized in intensely trained
      animals; moreover, they suggest that the observed desensitization is related to
      an increase of 5-HT-moduline tissue content; this mechanism may play a role in
      various pathophysiological conditions.

PMID- 10882035
TI  - Lidocaine potentiates the relaxant effects of cAMP-elevating agents in bovine
      tracheal smooth muscle.
AB  - The effect of lidocaine on the relaxation and accumulation of adenosine 3',5'
      cyclic monophosphate (cAMP) induced by salbutamol, forskolin and 3-isobutyl-1
      methylxanthine (IBMX) was examined in bovine tracheal smooth muscle preparations
      precontracted with methacholine (0.3 microM). Lidocaine attenuated the
      methacholine-induced contraction in a concentration-dependent manner.
      Pretreatment of the preparations with lidocaine (100 microM) caused significant
      leftwards shifts of concentration/response curves for the relaxant responses to
      salbutamol, forskolin, and IBMX, whereas it did not change the responses to
      diltiazem. Similar leftwards shifts were observed when the preparations were
      treated with procaine (6 microM) or bupivacaine (40 microM). Lidocaine (100
      microM) augmented cAMP accumulation induced by salbutamol (10 nM) and forskolin
      (1 microM). These results suggest that lidocaine augments the relaxant responses
      to cAMP-elevating agents through enhancement of cAMP accumulation.

PMID- 10882036
TI  - Estrogen directly acts on osteoclasts via inhibition of inward rectifier K+
      channels.
AB  - Using the whole-cell patch-clamp technique in freshly isolated rat osteoclasts we
      examined the effects of estrogen on ionic channels. The predominant current was
      an inward rectifier K+ current (IKir). In the absence of non-osteoclastic cells,
      extracellularly applied 17beta-estradiol (>0.1 microM) inhibited IKir, indicating
      that estrogen acts directly on osteoclasts. Application of 17beta-estradiol (10
      microM) for 10 min reduced IKir at the membrane potential of -120 mV to 70 +/-
      15% of control. Removal of 17beta-estradiol partially restored the inhibition.
      The inhibition of IKir was dependent on concentration and application time.
      Intracellularly applied 17beta-estradiol had no effect on IKir. 17alpha-estradiol
      also inhibited the IKir, whereas progesterone and testosterone had no effect. The
      inhibitory action of 17beta-estradiol was not affected by guanosine 5'-O-(2
      thiodiphosphate) (GDPbetaS), adenosine 3',5'-cyclic monophosphothioate Rp
      diastereomer (Rp-cAMPS), okadaic acid, staurosporine and phorbol ester, and was
      independent of intracellular Ca2+ concentration ([Ca2+]i). With no influence from
      soluble factors secreted from non-osteoclastic cells, preincubation of the
      osteoclasts for more than 60 min with much lower concentrations of 17beta
      estradiol (1 and 10 nM) caused a reduction of IKir. In current-clamp
      configuration, application of 17beta-estradiol (10 microM) depolarized the
      membrane associated with a decrease in a membrane conductance, indicating that
      17beta-estradiol inhibits IKir and depolarizes the membrane of osteoclasts. These
      results suggest that the 17beta-estradiol-induced inhibition of IKir might be
      mediated via non-genomic mechanisms. This direct action of 17beta-estradiol on
      osteoclasts may contribute to the regulation of [Ca2+]i and partially account for
      the protective effects of estrogen against bone loss.

PMID- 10882037
TI  - In rat alveolar macrophages lipopolysaccharides exert divergent effects on the
      transport of the cationic amino acids L-arginine and L-ornithine.
AB  - In rat alveolar macrophages (AMphi) it was tested whether induction of iNOS by
      lipopolysaccharides (LPS) is accompanied by changes in L-arginine transport and
      whether L-ornithine, the product of arginase released from AMphi, could, via
      inhibition of L-arginine uptake, act as a paracrine inhibitor of NO synthesis.
      Rat AMphi (cultured for 20 h in the absence or presence of 1 microg/ml LPS) were
      incubated in Krebs-HEPES solution containing [3H]-L-arginine (0.1 microM for 2
      min or 100 microM for 5 min) and the cellular radioactivity was determined as a
      measure of L-arginine uptake. In parallel, cells were incubated for 6 h in Krebs
      HEPES solution containing 0-1 mM L-arginine and nitrite accumulation was
      determined. [3H]-L-arginine uptake (0.1 microM or 100 microM) occurred
      independently of sodium ions and was inhibited by L-ornithine (EC50: 117 and 562
      microM, respectively) and with similar potencies by L-lysine. In LPS-treated
      AMphi the concentration inhibition curve of L-ornithine was shifted to the right
      by about a factor of 4, whereas that of L-lysine was only marginally shifted to
      the right. L-Leucine (0.1 and 1 mM) inhibited [3H]-L-arginine (0.1 microM) by 43
      and 58%, respectively, and the effect of 0.1 mM L-leucine was partially sodium
      dependent. In LPS-treated AMphi, 0.1 mM L-leucine no longer inhibited [3H]-L
      arginine and the effect of 1 mM L-leucine was attenuated. Kinetic analysis of the
      transport of [3H]-L-arginine and [14C]-L-ornithine revealed two components for
      each amino acid with Km values of 21 and 114 microM (L-arginine) and 39 and 1050
      microM (L-ornithine), respectively. After LPS treatment Km2 of L-arginine
      transport was reduced to 63 microM and Vmax of both components was increased,
      whereas Km2 of L-ornithine transport was enhanced to 1392 microM and Vmax1
      reduced. LPS-stimulated AMphi, incubated in amino acid-free Krebs-HEPES solution,
      produced about 4 nmol nitrite/10(6) cells per 6 h, and L-arginine enhanced
      nitrite accumulation maximally about threefold (EC50: 30 microM). L-ornithine, up
      to 3 mM, failed to affect significantly nitrite accumulation observed in the
      presence of 30 or 100 microM L-arginine. Rat AMphi express mRNA for two cationic
      amino acid transporters (CAT-1 and CAT-2B), and LPS markedly up-regulated mRNA
      for CAT-2B in parallel with mRNA for iNOS, but had no effect on that for CAT-1.
      In conclusion, in rat AMphi LPS up-regulates L-arginine transport and induces
      changes in the characteristics of the cationic amino acid transport resulting in
      preferential transport of L-arginine. These effects may be regarded as cellular
      measures to ensure a high L-arginine supply for iNOS.

PMID- 10882038
TI  - The AMPA/kainate receptor antagonist, LY 300164, increases the anticonvulsant
      effects of diazepam.
AB  - The aim of this study was to evaluate the influence of 7-acetyl-5-(4-aminophenyl)
      8,9-dihydro-8-methyl-7H-1,3-dioxolo(4,5 H)-2,3-benzodiazepine (LY 300164), a
      selective non-competitive antagonist at alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA)/kainate receptors, on the protection provided by diazepam
      against electrically- and chemically-evoked seizures in rodents. LY 300164 (2
      mg/kg) was devoid of any significant action upon each seizure parameter in
      kindled rats (seizure severity, seizure duration, after-discharge duration). LY
      300164 (5 mg/kg) exerted a significant anticonvulsive effect as regards seizure
      and after-discharge durations. Combined treatment with LY 300164 (2 mg/kg) and
      diazepam (0.3125-1.25 mg/kg) resulted in the clear-cut anticonvulsive activity.
      It is noteworthy that the antiseizure potency of the combined treatment (diazepam
      1.25 mg/kg plus LY 300164 2 mg/kg) was comparable to that of diazepam (10-20
      mg/kg) alone. The combination of diazepam (1.25 mg/kg) with LY 300164 (2 mg/kg)
      did not induce any significant motor impairment in the rotorod test or memory
      deficit in the passive-avoidance task. In contrast, diazepam alone (10-20 mg/kg)
      had pronounced adverse effects in kindled animals. LY 300164 (up to 2 mg/kg) did
      not influence the threshold for electro- and pentylenetetrazol-induced
      convulsions but potentiated the anticonvulsive action of diazepam in the maximal
      electroshock and pentylenetetrazol test in mice, the ED50s of the benzodiazepine
      being reduced from 13 to 8.7 and from 0.29 to 0.049 mg/kg, respectively. As shown
      in the passive-avoidance task, combination of LY 300164 (2 mg/kg) with diazepam
      (8.7 mg/ kg) produced significant motor and long-term memory impairment. Diazepam
      alone (at the dose equal to its ED50 against maximal electroshock) also caused
      motor and memory deficits in mice. Interaction at the pharmacokinetic level, at
      least in plasma, can be excluded, because LY 300164 (2 mg/kg) did not affect the
      free plasma diazepam concentration. In conclusion, LY 300164 potentiates the
      protective action of diazepam in some animal models of seizures. This profitable
      interaction may create a new approach for the treatment of drug resistant
      epilepsy or status epilepticus.

PMID- 10882039
TI  - Induction of cyclooxygenase-2 by platelet-derived growth factor (PDGF) and its
      inhibition by dexamethasone are independent of NF-kappaB/IkappaB transcription
      factors.
AB  - Glucocorticoids are potent inhibitors of cyclooxygenase-2 (prostaglandin G/H
      synthase-2, COX-2) expression. The focus of this work was to investigate the
      molecular mechanisms, by which glucocorticoids interfere with platelet-derived
      growth factor (PDGF)-mediated induction of COX-2 with special emphasis on the
      role of the transcription factors NF-kappaB/IkappaB alpha. In rat renal mesangial
      cells, PDGF induced a rapid and transient increase of COX-2 mRNA and protein,
      which reached maximal levels after 1-2 and 4 h, respectively. The in vivo half
      life of COX-2 mRNA, which was estimated to be less than 1 h, was reduced by
      dexamethasone. Kinetic studies and COX-2 promoter activity assays indicated that
      dexamethasone also interfered with COX-2 transcription. Inhibition of COX-2
      induction by dexamethasone was abrogated by cycloheximide, an inhibitor of
      translation, indicating dependence on de novo protein synthesis. As a possible
      mediator of dexamethasone action, the NF-kappaB/IkappaB alpha system of
      transcription factors was investigated. Dexamethasone doubled IkappaB alpha
      protein levels within 1 h and reduced complex formation of nuclear NF-kappaB
      proteins with DNA. Newly synthesized IkappaB alpha may thus bind to NF-kappaB and
      interfere with gene activation. PDGF-induced signalling, however, barely affected
      the NF-kappaB/IkappaB alpha system: IkappaB alpha protein remained unaltered for
      30 min after treatment of mesangial cells with PDGF and was only reduced by 30%
      after 1 h. Concomitantly, binding of NF-kappaB proteins to DNA, detected by
      electrophoretic mobility shift assays, was slightly increased by 30%.
      Furthermore, stably transfected COX-2 promoter constructs with and without the NF
      KB binding site were comparably activated by PDGF (2.5-fold increase of
      luciferase activity). Taken together, these data indicate that although
      dexamethasone interferes with the NF-kappaB/IkappaB alpha system of transcription
      factors, this mechanism is not essential for the inhibition of PDGF-induced COX-2
      expression.

PMID- 10882040
TI  - Effects of JTV-519, a novel anti-ischaemic drug, on the delayed rectifier K+
      current in guinea-pig ventricular myocytes.
AB  - We studied the effects of a newly synthesized anti-ischaemic agent, 4-[3-(4
      benzylpiperidin-1-yl) propionyl]-7-methoxy-2, 3, 4, 5-tetrahydro-1, 4
      benzothiazepine monohydrochloride (JTV-519) on the delayed rectifier potassium
      current (IK), using guinea-pig ventricular myocytes and whole-cell voltage-clamp
      techniques, under blockade of the L-type calcium current (ICa,L) by D600 (1
      microM) or nitrendipine (5 microM). The IK in guinea-pig ventricular cells
      consists of two different components; the rapidly activating, E4031-sensitive
      component (IKr) and the slowly activating E4031-resistant component (IKs). Under
      steady-state conditions, JTV-519 (1 and 5 microM) did not change the amplitude of
      IKs remaining after blockade of IKr with 5 microM E4031. The effect of JTV-519 on
      IKr was assessed using short (50 ms) pulses which evoked a tail current that was
      sensitive to E4031 but not to chromanol 293B, a specific blocker of IKs. JTV-519
      suppressed the IKr with a half-maximal inhibitory concentration of 1.2 microM.
      Selective inhibition of IKr by this agent was confirmed by using the "envelope of
      tails" test. These results suggest that the blockade of IKr may underlie the
      prolongation of action potential duration in ventricular muscle and QT-intervals
      alleged to occur in animal as well as human hearts.

PMID- 10882041
TI  - Acidic dopamine metabolites are actively extruded from PC12 cells by a novel
      sulfonylurea-sensitive transporter.
AB  - Incubation of PC 12 cells with the sulfonylurea drug, glipizide (1-100 microM),
      increased intracellular levels of the acidic metabolites of dopamine, 3,4
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The levels of
      these acids in the medium were decreased, indicating the presence of a
      sulfonylurea-sensitive organic anion transporter. In the present study, we
      demonstrate that the sulfonylurea-sensitive transport of acidic dopamine
      metabolites is unidirectional, ATP dependent, unaffected by ouabain or by
      tetrodotoxin and blocked by drugs that interact with the multidrug-resistance
      protein-1 (MRP1). However, over-expression of MRP1 did not affect transport of
      the acid metabolites. The pharmacological profile and ion dependence of the
      transporter also differs from that of known ATP-binding cassette (ABC) family
      members. Using microdialysis, we also demonstrated a sulfonylurea-sensitive
      transport process in the striatum of freely moving rats. These results show that
      acidic dopamine metabolites are actively secreted from dopaminergic cells into
      surrounding extracellular fluid by a previously undescribed transporter.

PMID- 10882042
TI  - Further pharmacological analysis of the orphan 5-HT receptors mediating feline
      vasodepressor responses: close resemblance to the 5-HT7, receptor.
AB  - It has been suggested that the late hypotensive response to serotonin (5
      hydroxytryptamine; 5-HT) in vagosympathectomised cats, being potently mimicked by
      5-carboxamidotryptamine (5-CT), not modified by ketanserin and blocked by
      methiothepin or methysergide, is mediated by '5-HT1-like' receptors.
      Nevertheless, current guidelines for 5-HT receptor classification refer to this
      receptor as an orphan receptor. Thus, the present study set out to reanalyse the
      above suggestion in terms of the classification schemes proposed in 1994 and 1998
      by the NC-IUPHAR subcommittee on the classification of 5-HT receptors.
      Intravenous (i.v.) bolus injections of 5-CT (0.003-0.3 microg/kg), 5-HT (1-100
      microg/kg) and 5-methoxytryptamine (5-MeO-T; 1-100 microg/kg) produced dose
      dependent vasodepressor responses with a rank order of agonist potency of 5-CT >>
      5-HT = 5-MeO-T with sumatriptan (10-300 microg/kg) virtually inactive. The
      vasodepressor responses to 5-HT, 5-CT and 5-MeO-T were not attenuated following
      i.v. administration of the antagonists GR127935 (5-HT(IB/ID); 30 microg/kg),
      tropisetron (5-HT3/4; 3000 microg/kg), (+/-)-pindolol (beta-adrenergic and 5
      HT1A; 4000 microg/kg) or equivalent volumes of physiological saline. In contrast,
      the above vasodepressor responses were markedly and specifically antagonised by
      i.v. methiothepin (100 microg/kg), lisuride (30 microg/kg and 100 microg/kg),
      mesulergine (300 microg/kg and 1000 microg/kg) or LY215840 (300 microg/kg and
      1000 microg/kg). The above lines of evidence, therefore, indicate that the orphan
      receptors mediating the vasodepressor responses to 5-HT in vagosympathectomised
      cats are pharmacologically similar to other 5-HT7 receptors mediating vascular
      and non-vascular responses (e.g. relaxation of the canine external carotid artery
      and guinea-pig ileum as well as feline tachycardia).

PMID- 10882043
TI  - Agonist efficacy at the alpha2A-adrenoceptor:G alpha15 fusion protein: an
      analysis based on Ca2+ responses.
AB  - A fusion protein was constructed between the recombinant human alpha2A
      adrenoceptor and a mouse G alpha15 protein to measure the efficacy of agonist
      induced Ca2+ responses at a receptor:G alpha15 protein stoichiometry of 1.
      Activation of this fusion protein in CHO-K1 cells by (-)-adrenaline induced a
      time- and concentration-dependent (pEC50: 7.28+/-0.04) increase in the
      intracellular Ca2+ concentration. The magnitude of the Ca2+ response was related
      to the amount of the fusion protein and the number of surface alpha2A
      adrenoceptor binding sites as estimated by [3H]RX 821002 binding. Whereas UK
      14304 was as efficacious as (-)-adrenaline, the following ligands displayed
      partial agonist properties [Emax in percentage vs. (-)-adrenaline: d-medetomidine
      (76+/-3) > BHT 920 (53+/-3) > clonidine (39+/-4) >> oxymetazoline (10+/-1)]. This
      ligand activation profile was not affected over a 30-fold range of expression of
      the fusion protein in contrast to the observed enhancement of the partial
      agonists' maximal responses by co-expression of the alpha2A-adrenoceptor with
      increasing amounts of the G alpha15 protein. In conclusion, the fusion protein
      approach opens perspectives to quantify intrinsic activities of ligands under
      controlled experimental conditions of a fixed receptor:G alpha15 protein ratio of
      1.

PMID- 10882044
TI  - Immittance and otoacoustic emissions in rhesus monkeys and humans.
AB  - The purpose of this study was to compare multifrequency tympanometry and
      otoacoustic emissions (OAEs) in rhesus monkeys (Macaca mulatta) and humans.
      Tympanometry and OAEs can be recorded efficiently in Macaca mulatta to assess
      peripheral auditory function with results comparable to those in humans.
      Differences include (1) greater admittances and conductances in humans from 226
      to 630 Hz, the frequency range validly assessed; (2) larger amplitude transient
      evoked OAEs (TEOAEs) and noise levels in humans; (3) larger amplitude monkey
      2f(1)-f(2) distortion product OAEs (DPOAES) (f(2)s>2 kHz); (4) more prominent
      DPOAEs other than 2f(1)-f(2) in monkeys; (5) more narrowly tuned human f(2)/f(1)
      X 2f(1)-f(2) amplitude functions at the lower frequencies tested; and (6) lower
      2f(1)-f(2) DPOAE thresholds at f(2)=0.5 kHz and > or = 8 kHz in monkeys.

PMID- 10882045
TI  - Comparison of neonatal transient evoked otoacoustic emission responses recorded
      with linear and QuickScreen protocols.
AB  - Linear and QuickScreen (non-linear) transient evoked otoacoustic emission (TEOAE)
      protocols were compared in terms of standardized clinical parameters in order to
      define the protocol producing recordings with the highest signal quality.
      Neonatal responses (520) were obtained from three different screening sites. The
      linear recordings were evoked by 69 and 75-dB p.e. SPL clicks. All responses were
      post-windowed by a 3.5- to 12.5-ms window, chosen by time-frequency analysis as
      the segment representing 97.35 per cent (linear) and 95.6 per cent (quick) of the
      total cumulative spectral energy. Evidence from hearing loss cases and the high
      similarity between the profile contours of the QuickScreen and the linear normal
      recordings have strongly suggested that a linear response evoked by a 75-dB p.e.
      SPL stimulus and post-processed by a 3.5 to 12.5 window is free of stimulus
      artefacts. The data indicate that the 75-dB linear protocol produces higher
      signal to noise ratios at 2.0, 3.0, and 4.0 kHz, higher wave reproducibility, and
      lower TEOAE noise values than the QuickScreen protocol.

PMID- 10882046
TI  - Auditory brainstem responses in Rett syndrome: effects of hyperventilation,
      seizures, and tympanometric variables.
AB  - This study examined the effects of tympanometric variables, stage of disease,
      hyperventilation, and seizures on the auditory brainstem response (ABR) in Rett
      syndrome (RS). Thirty-four female children with RS ranging in age from 2 years, 3
      months to 15 years, 7 months participated in the study. ABRs and tympanograms
      were recorded from all of the subjects. When the ABR peaks were identifiable,
      interpeak latency intervals (IPLIs) for I-III, III-V, and I-V were computed for
      each waveform. The peaks (I, III, and V) and IPLIs were characterized as abnormal
      if either the peaks were absent or the latencies were greater than 2 SD from the
      normative data (obtained on female children). Analyses revealed significant
      prolongation of wave I latencies in Rett children with abnormal tympanograms. ABR
      wave III latencies were significantly affected by the presence of seizures and
      hyperventilation. The Pearson chi-square statistic revealed significant
      differences in the rate of wave III and V abnormalities due to the presence and
      degree of hyperventilation and the presence of seizures. Wave I abnormalities
      were also observed in the presence of normal middle ear function, suggesting the
      presence of sensorineural hearing impairment in some RS children. Clinical
      implications of these findings are discussed.

PMID- 10882047
TI  - Social competence and behavioural problems in children with hearing impairment.
AB  - The focus in this study is on social competence and behavioural problems in a
      group (n=57) of hearing-impaired 7- to 12-year-old children. Results were related
      to hearing status, school placement, and gender. Parent and teacher
      questionnaires were used to measure two aspects of social competence, prosocial
      orientation and social initiative, and three aspects of behavioural problems,
      externalizing, internalizing, and concentration problems. A sample of 214
      normally-hearing children was used as a comparison group. Overall, the results
      showed only minor differences between the two groups, with the exception that the
      hearing-impaired children showed less social initiative in parent ratings. There
      were no relationships between social functioning and hearing status or school
      placement (mainstream vs. special classes for hearing-impaired children) nor any
      clear pattern of gender differences. These findings indicate that hearing
      impaired children in Sweden fare well. The results are discussed in terms of the
      need for longitudinal studies and possible interventions targeted at social
      behaviours.

PMID- 10882048
TI  - Effect of order bias on the recognition of dichotic digits in young and elderly
      listeners.
AB  - Dichotic listening was evaluated in free-recall and directed-recall (pre-cued,
      post-cued) response conditions using interleaved one-, two-, and three-pair
      dichotic digit materials. In the free-recall condition, the subjects recalled in
      any order the digits presented. In the directed-recall condition, a response task
      was examined where subjects recalled all digits presented to the cued ear (pre-
      or post-cued) followed by the digits presented to the opposite (non-cued) ear.
      Thirty 20- to 29-year-old adults with normal hearing and 30 60- to 79-year-old
      adults with mild-to-moderate sensorineural hearing loss were evaluated. In all
      conditions, performance by the younger listeners was better than performance by
      the elderly listeners. As the difficulty of the dichotic digit task increased,
      recognition performance decreased. The recognition performance of elderly
      listeners was more affected by increases in the difficulty of the stimulus
      materials as compared to the younger listeners. In the free-recall condition,
      there was a right-ear advantage for both age groups. When instructional bias was
      imposed, the results favored the ear of instructed bias. The differences in
      recognition performance between young and elderly listeners likely reflect
      differences in the difficulty of the dichotic digit test conditions and
      variations in the demand on auditory memory.

PMID- 10882049
TI  - Short-term effect of auditory feedback on fundamental frequency after cochlear
      implantation.
AB  - The present study evaluates the short-term effect of cochlear implantation on the
      fundamental frequency (FO) of 13 deaf patients. All patients were provided with
      the Combi 40+ cochlear implant. Voice recording was made pre- and 3 months post
      implantation. The FO was analysed using X-Tools software. The results showed that
      38 per cent of our subjects had a statistically significant decrease of their
      mean F0 (p=0.001) at 3 months following implantation. It was also observed that
      the patients tended to have a lower F0 postoperatively approaching the normal
      range of F0. A large variability in F0 was noticed among the deaf subjects but no
      correlation with the duration of deafness was seen. There was also no correlation
      between speech recognition and speech production.

PMID- 10882050
TI  - Tone detection in Mandarin-speaking hearing-impaired subjects.
AB  - The ability of native Mandarin-speaking, hearing-impaired subjects to detect
      Mandarin tones was assessed in this study. Nine subjects with mild sensorineural
      hearing loss (SNHL) and nine subjects with moderate SNHL participated in the
      study. Nine normal subjects served as control. All subjects received a tone
      detection test and Chinese word recognition test. The results show that tone
      detection was only minimally impaired in the mild SNHL group if audibility of the
      stimulus is well compensated for. In the moderate SNHL group, the mean score was
      significantly lower, but the difference was small. This suggests that tone
      detection is only slightly impaired for subjects with moderate hearing loss. For
      each individual tone, the mean scores for tones 2 and 3 were lowest and most
      easily confused by all normal and hearing-impaired subjects. No significant
      correlation was found between the tone detection score and word recognition score
      for all subjects. The relatively preserved ability to perceive tones in mild and
      moderate SNHL subjects may be helpful in their speech recognition.

PMID- 10882051
TI  - Over-the-counter hearing aids: electroacoustic characteristics and possible
      target client groups.
AB  - Over-the-counter hearing aids (OTCs) are those directly purchased from retail
      outlets, without the benefit of prior professional hearing health care. They are
      particularly common in developing countries. This study examined the
      amplification characteristics of a selected sample of OTCs to determine if any
      target client group or groups were suitable for the OTCs. The electroacoustical
      performance of 10 OTCs was measured. The measurements included saturated sound
      pressure level curve, high-frequency average full-on gain, frequency response,
      total harmonic distortion, equivalent input noise level, and input-output curve.
      The full-on gain curve of each hearing aid was used to estimate the hypothetical
      hearing loss of target clients for each aid as it would be calculated by four
      hearing aid prescription formulae. Real-ear probe tube measurements were also
      performed on 10 adult subjects to determine the amplification that could be
      achieved by the OTCs before audible feedback occurred. The OTC hearing aids were
      not able to meet the prescription gain requirements of the majority of elderly
      clients who usually purchased them.

PMID- 10882052
TI  - Driver clones and determinant spreading.

PMID- 10882053
TI  - Despite epitope spreading in the pathogenesis of autoimmune disease, highly
      restricted approaches to immune therapy may still succeed [with a hedge on this
      bet].

PMID- 10882054
TI  - Restricted and shared patterns of TCR beta-chain gene expression in silicone
      breast implant capsules and remote sites of tissue inflammation.
AB  - Silicone breast implants (SBI) induce formation of a periprosthetic, often
      inflammatory, fibrovascular neo-tissue called a capsule. Histopathology of
      explanted capsules varies from densely fibrotic, acellular specimens to those
      showing intense inflammation with activated macrophages, multinucleated giant
      cells, and lymphocytic infiltrates. It has been proposed that capsule
      infiltrating lymphocytes comprise a secondary, bystander component of an
      otherwise benign foreign body response in women with SBIs. In symptomatic women
      with SBIs, however, the relationship of capsular inflammation to inflammation in
      other remote tissues remains unclear. In the present study, we utilized a
      combination of TCR beta-chain CDR3 spectratyping and DNA sequence analysis to
      assess the clonal heterogeneity of T cells infiltrating SBI capsules and remote,
      inflammatory tissues. TCR CDR3 fragment analysis of 22 distinct beta variable
      (BV) gene families revealed heterogeneous patterns of T cell infiltration in
      patients' capsules. In some cases, however, TCR BV transcripts exhibiting
      restricted clonality with shared CDR3 lengths were detected in left and right SBI
      capsules and other inflammatory tissues. DNA sequence analysis of shared, size
      restricted CDR3 fragments confirmed that certain TCR BV transcripts isolated from
      left and right SBI capsules and multiple, extracapsular tissues had identical
      amino acid sequences within the CDR3 antigen binding domain. These data suggest
      that shared, antigen-driven T cell responses may contribute to chronic
      inflammation in SBI capsules as well as systemic sites of tissue injury.

PMID- 10882055
TI  - Potent adjuvant effect by anti-CD40 in collagen-induced arthritis. Enhanced
      disease is accompanied by increased production of collagen type-II reactive IgG2a
      and IFN-gamma.
AB  - Collagen type II-induced arthritis (CIA) is an experimental model of rheumatoid
      arthritis, an autoimmune inflammatory disease of the peripheral joints in humans.
      CD40 interaction with its ligand CD154 (CD40L) has been shown to be an obligatory
      step in the initiation of autoimmune disease in several animal models. In this
      study we report on the effect of CD40 stimulation in CIA induced by immunization
      with type II collagen (CII) in CFA or IFA. We found that the administration of
      stimulatory anti-CD40 mAb resulted in earlier onset and more severe disease in
      IFA-CII-immunized mice. The mAb treatment resulted in markedly elevated titers of
      CII-specific IgG2a antibodies whereas CII-specific IgG1 titers were unaffected.
      Draining lymph node cell cultures from mice treated with anti-CD40 exhibited
      significantly increased IFN-gamma production compared to cultures from control
      antibody-treated mice. In conclusion, our results indicate that the level of CD40
      activation during the induction of an autoimmune response may determine the
      severity of the resulting disease.

PMID- 10882056
TI  - Dimethyl dioctadecyl ammonium bromide (DDA)-induced arthritis in rats: a model of
      experimental arthritis.
AB  - A single intradermal injection of 2 mg of dimethyl dioctadecyl ammonium bromide
      (DDA) in phosphate buffered saline (PBS) could induce polyarthritis in both LEW
      and DA rats with low incidence and severity whereas 2 mg of DDA in incomplete
      Freund's adjuvant (IFA) could induce very severe polyarthritis with 100%
      incidence in LEW rats. Histology of DDA-induced arthritis (DIA) revealed cellular
      infiltration, synovial hypertrophy, development of granulation tissue,
      destruction of cartilage and bone deformation in the articular joints. Lymph node
      cells (LNCs) but not immunoglobulin fractions from the DIA rats successfully
      transferred the severe disease into the naive recipients. A challenge injection
      of DDA in IFA in the rats, which had recovered from the DIA, could reactivate the
      disease. It is thus concluded that DDA has arthritis-inducing ability in the rats
      which is potentiated by IFA and the DIA is a cell-mediated immune disease which
      might be a model of experimental arthritis.

PMID- 10882057
TI  - Relapsing and remitting experimental autoimmune encephalomyelitis in B cell
      deficient mice.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human
      autoimmune central nervous system (CNS) disease multiple sclerosis (MS). To
      examine the role of B cells in EAE with a relapsing and remitting disease course
      (R-EAE) we generated (B10.PL x SJL/J)F1 mice deficient in B cells by disrupting
      their mu heavy chain transmembrane region (B10.PL x SJL/J)F1 muMT-/-. By
      immunizing (B10.PL x SJL/J)F1 and (B10.PL x SJL/J)F1 muMT-/- mice with the
      encephalitogenic N-terminal peptide Acl-11 of myelin basic protein (MBP), we
      observed that B-cell deficient mice exhibited a relapsing and remitting disease
      course. Since a similar day of onset and day of first relapse were observed these
      data suggest that B cells do not play a vital role in the activation of T cells
      leading to the initiation of EAE, nor in the reactivation of T cells resulting in
      R-EAE.

PMID- 10882058
TI  - Serum IgM repertoire reactions to MBP/CFA immunization reflect the individual
      status of EAE susceptibility.
AB  - Lewis rats develop experimental allergic encephalomyelitis (EAE) in response to
      immunization with myelin basic protein (MBP) in CFA, while Fischer rats are
      usually resistant. These strains, while comparably producing anti-MBP antibodies,
      also differ in their repertoire reactions to immunization, as measured by
      patterns of serum IgM reactivity with various autologous proteins. We have now
      scored IgM repertoire reactions to MBP/CFA immunization after treatments that
      alter EAE susceptibility in either strain. The results show that abrogation of
      EAE susceptibility in Lewis rats by a previous experience of T cell-induced
      passive EAE provoked a novel set of IgM reactivities that otherwise characterized
      the Fischer's repertoire reaction. Conversely, these reactivities were delayed in
      the response of Fischer rats that had been rendered EAE-susceptible by
      cyclophosphamide. Another IgM reactivity with a significant association to
      individual EAE severity in Lewis rats behaved reciprocally. Together with
      previous results, these observations suggest that putative regulatory mechanisms
      concordantly affect EAE resistance and IgM repertoire reactions, operating
      naturally in Fischer rats and abrogatable by cyclophosphamide treatment, whereas
      naturally suppressed, but restorable in Lewis rats. Other treatments altering EAE
      susceptibility, however, did not share these characteristics and may thus be
      mediated by other mechanisms.

PMID- 10882059
TI  - Altered circadian rhythms of the stress hormone and melatonin response in lupus
      prone MRL/MP-fas(Ipr) mice.
AB  - The immune system interacts with the hypothalamo-pituitary-adrenal axis via so
      called glucocorticoid increasing factors, which are produced by the immune system
      during immune reactions, causing an elevation of systemic glucocorticoid levels
      that contribute to preservation of the immune reactions specificities. Previous
      results from our laboratory had already shown an altered immuno-neuroendocrine
      dialogue via the hypothalamo-pituitary-adrenal axis in autoimmune disease-prone
      chicken and mouse strains. In the present study, we further investigated the
      altered glucocorticoid response via the hypothalamo-pituitary-adrenal axis in
      murine lupus. We established the circadian rhythms of corticosterone,
      dehydroepiandrosterone-sulfate, adrenocorticotropic hormone and melatonin, as
      well as the time response curves after injection of interleukin-1 of the first
      three parameters in normal SWISS and lupus-prone MRL/MP-fas(Ipr) mice. The
      results show that lupus-prone MRL/ MP-fas(Ipr) mice do not react appropriately to
      changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple
      from the light/dark cycle, and plasma corticosterone levels are elevated during
      the resting phase. Diurnal changes of dehydroepiandrosterone-sulfate and
      adrenocorticotropic hormone were normal compared to healthy controls. These data
      indicate that MRL/ MP-fas(Ipr) mice not only show an altered glucocorticoid
      response mediated via the hypothalamo pituitary adrenal axis to IL-1, but are
      also affected by disturbances of corticosterone and melatonin circadian rhythms.
      Our findings may have implications for intrathymic T cell development and the
      emergence of autoimmune disease.

PMID- 10882060
TI  - 'Anergic' T cells modulate the T-cell activating capacity of antigen-presenting
      cells.
AB  - Nowadays there is compelling evidence for immunoregulation by T cells. Recently,
      we showed that so-called 'anergic' T cells are not functionally inert but can act
      as regulatory cells by actively suppressing other T cell responses. We now show
      that 'anergic' T cells mediate this suppressive effect via modulation of the T
      cell activating capacity of the antigen-presenting cell (APC). Upon removal of
      the 'anergic' T cells, the suppressive APC phenotype persisted, indicating that
      'anergic' T cells conditioned the APC to become a mediator of T cell suppression.
      The inhibitory signal delivered by 'anergic' T cells depended on the presence of
      the cognate ligand for the 'anergic' T cell, and appeared to be dominant since
      previously activated APC were rendered inhibitory as well. These findings imply
      that APC upon cross-talk with T cells can adopt distinct functional phenotypes
      ranging from T-cell stimulatory to T-cell suppressive. The contribution of
      'anergic' T cells to the functional tuning of APC offers an explanation for the
      maintenance of 'anergic' T cells in the repertoire, and for their role in
      immunoregulation.

PMID- 10882061
TI  - Biochemical characterization of a beta cell membrane fraction antigenic for
      autoreactive T cell clones.
AB  - The two NOD-derived T cell clones, BDC-2.5 and BDC-6.9, are CD4+, Vbeta4+, islet
      specific, and diabetogenic. These two T cell clones show different response
      patterns to whole islet cell antigen, but were found to respond to the same
      fraction isolated from beta granule membranes. The clones were used to follow the
      antigenic activity in the biochemical purification of a beta cell membrane
      detergent lysate subjected to HPLC anion exchange (IEX) and size exclusion
      chromatography (SEC). Antigenic activity could be retained after lysis in only
      one detergent (octyl-beta-glucoside) among several tested. In order to detect
      solubilized antigen, beta membrane proteins were covalently linked to microlatex
      beads prior to being added to T cell proliferation assays, a technique that
      eliminated detergent toxicity and resulted in increased assay sensitivity. To
      purify the antigen, membrane proteins were absorbed onto an anion exchange column
      and after elution using a salt gradient, activity for the clones was found in a
      fraction containing 0.15-0.2 M NaCl. Subsequent analysis of this material by size
      exclusion chromatography provided an apparent molecular weight of the antigen to
      be between 50 and 80 kDa. Further attempts to purify the protein by SDS-PAGE
      resulted in loss of antigenic activity. It is possible that the elusive nature of
      this protein is a clue to its importance as an autoantigen.

PMID- 10882062
TI  - A ligand-induced extracellular cleavage regulates gamma-secretase-like
      proteolytic activation of Notch1.
AB  - Gamma-secretase-like proteolysis at site 3 (S3), within the transmembrane domain,
      releases the Notch intracellular domain (NICD) and activates CSL-mediated Notch
      signaling. S3 processing occurs only in response to ligand binding; however, the
      molecular basis of this regulation is unknown. Here we demonstrate that ligand
      binding facilitates cleavage at a novel site (S2), within the extracellular
      juxtamembrane region, which serves to release ectodomain repression of NICD
      production. Cleavage at S2 generates a transient intermediate peptide termed NEXT
      (Notch extracellular truncation). NEXT accumulates when NICD production is
      blocked by point mutations or gamma-secretase inhibitors or by loss of presenilin
      1, and inhibition of NEXT eliminates NICD production. Our data demonstrate that
      S2 cleavage is a ligand-regulated step in the proteolytic cascade leading to
      Notch activation.

PMID- 10882063
TI  - A novel proteolytic cleavage involved in Notch signaling: the role of the
      disintegrin-metalloprotease TACE.
AB  - The Notch1 receptor is presented at the cell membrane as a heterodimer after
      constitutive processing by a furin-like convertase. Ligand binding induces the
      proteolytic release of Notch intracellular domain by a gamma-secretase-like
      activity. This domain translocates to the nucleus and interacts with the DNA
      binding protein CSL, resulting in transcriptional activation of target genes.
      Here we show that an additional processing event occurs in the extracellular part
      of the receptor, preceding cleavage by the gamma-secretase-like activity.
      Purification of the activity accounting for this cleavage in vitro shows that it
      is due to TACE (TNFalpha-converting enzyme), a member of the ADAM (a disintegrin
      and metalloprotease domain) family of metalloproteases. Furthermore, experiments
      carried out on TACE-/- bone marrow-derived monocytic precursor cells suggest that
      this metalloprotease plays a prominent role in the activation of the Notch
      pathway.

PMID- 10882064
TI  - Xenopus embryonic E2F is required for the formation of ventral and posterior cell
      fates during early embryogenesis.
AB  - Using an expression cloning approach, we have unveiled a novel function for the
      transcription factor E2F. We demonstrate that Xenopus E2F (xE2F) is required for
      patterning of the Xenopus embryonic axis. Overexpression of xE2F in embryos
      induces ectopic expression of ventral and posterior markers, including selected
      members of the Hox genes, and suppresses the development of dorsoanterior
      structures. Loss of xE2F function in embryos leads to the elimination of ventral
      and posterior structures. These observations suggest that xE2F acts as an
      important regulator of region-specific gene expression and in the formation of
      the embryonic axis. This study provides evidence for an additional embryonic
      function for E2F, independent of its well-documented role in cell cycle
      regulation, and suggests a novel mechanism of region-specific gene expression
      during vertebrate embryogenesis.

PMID- 10882065
TI  - The Drosophila SHC adaptor protein is required for signaling by a subset of
      receptor tyrosine kinases.
AB  - Receptor tyrosine kinases (RTKs) transduce signals via cytoplasmic adaptor
      proteins to downstream signaling components. We have identified loss-of-function
      mutations in dshc, the Drosophila homolog of the mammalian adaptor protein SHC. A
      point mutation in the phosphotyrosine binding (PTB) domain completely abolishes
      DSHC function and provides in vivo evidence for the function of PTB domains.
      Unlike other adaptor proteins, DSHC is involved in signaling by only a subset of
      RTKs: dshc mutants show defects in Torso and DER but not Sevenless signaling,
      which is confirmed by epistasis experiments. We show by double-mutant analysis
      that the adaptors DOS, DRK, and DSHC act in parallel to transduce the Torso
      signal. Our results suggest that DSHC confers specificity to receptor signaling.

PMID- 10882066
TI  - Cohesin's binding to chromosomes depends on a separate complex consisting of Scc2
      and Scc4 proteins.
AB  - Cohesion between sister chromatids depends on a multisubunit cohesin complex that
      binds to chromosomes around DNA replication and dissociates from them at the
      onset of anaphase. Scc2p, though not a cohesin subunit, is also required for
      sister chromatid cohesion. We show here that Scc2p forms a complex with a novel
      protein, Scc4p, which is also necessary for sister cohesion. In scc2 or scc4
      mutants, cohesin complexes form normally but fail to bind both to centromeres and
      to chromosome arms. Our data suggest that a major role for the Scc2p/Scc4p
      complex is to facilitate the loading of cohesin complexes onto chromosomes.

PMID- 10882067
TI  - Cryo-electron microscopy reveals the functional organization of an enveloped
      virus, Semliki Forest virus.
AB  - Semliki Forest virus serves as a paradigm for membrane fusion and assembly. Our
      icosahedral reconstruction combined 5276 particle images from 48 cryo-electron
      micrographs and determined the virion structure to 9 A resolution. The improved
      resolution of this map reveals an N-terminal arm linking capsid subunits and
      defines the spike-capsid interaction sites. It illustrates the paired helical
      nature of the transmembrane segments and the elongated structures connecting them
      to the spike projecting domains. A 10 A diameter density in the fusion protein
      lines the cavity at the center of the spike. These clearly visible features
      combine with the variation in order between the layers to provide a framework for
      understanding the structural changes during the life cycle of an enveloped virus.

PMID- 10882068
TI  - The crystal structure of an unusual processivity factor, herpes simplex virus
      UL42, bound to the C terminus of its cognate polymerase.
AB  - Herpes simplex virus DNA polymerase is a heterodimer composed of a catalytic
      subunit, Pol, and an unusual processivity subunit, UL42, which, unlike
      processivity factors such as PCNA, directly binds DNA. The crystal structure of a
      complex of the C-terminal 36 residues of Pol bound to residues 1-319 of UL42
      reveals remarkable similarities between UL42 and PCNA despite contrasting
      biochemical properties and lack of sequence homology. Moreover, the Pol-UL42
      interaction resembles the interaction between the cell cycle regulator p21 and
      PCNA. The structure and previous data suggest that the UL42 monomer interacts
      with DNA quite differently than does multimeric toroidal PCNA. The details of the
      structure lead to a model for the mechanism of UL42, provide the basis for drug
      design, and allow modeling of other proteins that lack sequence homology with
      UL42 or PCNA.

PMID- 10882069
TI  - Capture and visualization of a catalytic RNA enzyme-product complex using crystal
      lattice trapping and X-ray holographic reconstruction.
AB  - We have determined the crystal structure of the enzyme-product complex of the
      hammerhead ribozyme by using a reinforced crystal lattice to trap the complex
      prior to dissociation and by employing X-ray holographic image reconstruction, a
      real-space electron density imaging and refinement procedure. Subsequent to
      catalysis, the cleavage site residue (C-17), together with its 2',3'-cyclic
      phosphate, adopts a conformation close to and approximately perpendicular to the
      Watson-Crick base-pairing faces of two highly conserved purines in the ribozyme's
      catalytic pocket (G-5 and A-6). We observe several interactions with functional
      groups on these residues that have been identified as critical for ribozyme
      activity by biochemical analyses but whose role has defied explanation in terms
      of previous structural analyses. These interactions may therefore be relevant to
      the hammerhead ribozyme reaction mechanism.

PMID- 10882070
TI  - Crystal structure of a heterodimeric complex of RAR and RXR ligand-binding
      domains.
AB  - The crystal structure of a heterodimer between the ligand-binding domains (LBDs)
      of the human RARalpha bound to a selective antagonist and the constitutively
      active mouse RXRalphaF318A mutant shows that, pushed by a bulky extension of the
      ligand, RARalpha helix H12 adopts an antagonist position. The unexpected presence
      of a fatty acid in the ligand-binding pocket of RXRalpha(F318A is likely to
      account for its apparent "constitutivity." Specific conformational changes
      suggest the structural basis of pure and partial antagonism. The RAR-RXR
      heterodimer interface is similar to that observed in most nuclear receptor (NR)
      homodimers. A correlative analysis of 3D structures and sequences provides a
      novel view on dimerization among members of the nuclear receptor superfamily.

PMID- 10882071
TI  - A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral
      transfer of iron to the circulation.
AB  - Iron absorption by the duodenal mucosa is initiated by uptake of ferrous Fe(II)
      iron across the brush border membrane and culminates in transfer of the metal
      across the basolateral membrane to the portal vein circulation by an unknown
      mechanism. We describe here the isolation and characterization of a novel cDNA
      (Ireg1) encoding a duodenal protein that is localized to the basolateral membrane
      of polarized epithelial cells. Ireg1 mRNA and protein expression are increased
      under conditions of increased iron absorption, and the 5' UTR of the Ireg1 mRNA
      contains a functional iron-responsive element (IRE). IREG1 stimulates iron efflux
      following expression in Xenopus oocytes. We conclude that IREG1 represents the
      long-sought duodenal iron export protein and is upregulated in the iron overload
      disease, hereditary hemochromatosis.

PMID- 10882072
TI  - CEA-related cell adhesion molecule 1: a potent angiogenic factor and a major
      effector of vascular endothelial growth factor.
AB  - CEA-related cell adhesion molecule 1 (CEACAM1) exhibits angiogenic properties in
      in vitro and in vivo angiogenesis assays. CEACAM1 purified from granulocytes and
      endothelial cell media as well as recombinant CEACAM1 expressed in HEK293 cells
      stimulate proliferation, chemotaxis, and capillary-like tube formation of human
      microvascular endothelial cells. They increase vascularization of chick
      chorioallantoic membrane and potentiate the effects of vascular endothelial
      growth factor (VEGF)165. VEGF165 increases CEACAM1 expression both on the mRNA
      and the protein level. VEGF165-induced endothelial tube formation is blocked by a
      monoclonal CEACAM1 antibody. These data suggest that CEACAM1 is a major effector
      of VEGF in the early microvessel formation. Since CEACAM1 is expressed in tumor
      microvessels but not in large blood vessels, CEACAM1 may be a target for the
      inhibition of tumor angiogenesis.

PMID- 10882073
TI  - An ATPase/helicase complex is an essential cofactor for oncogenic transformation
      by c-Myc.
AB  - The c-Myc transactivation domain was used to affinity purify tightly associated
      nuclear proteins. Two of these proteins were identified as TIP49 and a novel
      related protein called TIP48, both of which are highly conserved in evolution and
      contain ATPase/helicase motifs. TIP49 and TIP48 are complexed with c-Myc in vivo,
      and binding is dependent on a c-Myc domain essential for oncogenic activity. A
      missense mutation in the TIP49 ATPase motif acts as a dominant inhibitor of c-Myc
      oncogenic activity but does not inhibit normal cell growth, indicating that
      functional TIP49 protein is an essential mediator of c-Myc oncogenic
      transformation. The TIP49 and TIP48 ATPase/helicase proteins represent a novel
      class of cofactors recruited by transcriptional activation domains that function
      in diverse pathways.

PMID- 10882074
TI  - The FBP interacting repressor targets TFIIH to inhibit activated transcription.
AB  - FUSE-binding protein (FBP) binds the single-stranded far upstream element of
      active c-myc genes, possesses potent transcription activation and repression
      domains, and is necessary for c-myc expression. A novel 60 kDa protein, the FBP
      interacting repressor (FIR), blocked activator-dependent, but not basal,
      transcription through TFIIH. Recruited through FBP's nucleic acid-binding domain,
      FIR formed a ternary complex with FBP and FUSE. FIR repressed a c-myc reporter
      via the FUSE. The amino terminus of FIR contained an activator-selective
      repression domain capable of acting in cis or even in trans in vivo and in vitro.
      The repression domain of FIR targeted only TFIIH's p89/XPB helicase, required at
      several stages in transcription, but not factors required for promoter selection.
      Thus, FIR locks TFIIH in an activation-resistant configuration that still
      supports basal transcription.

PMID- 10882075
TI  - E2A and EBF act in synergy with the V(D)J recombinase to generate a diverse
      immunoglobulin repertoire in nonlymphoid cells.
AB  - Immunoglobulin (Ig) and T cell receptor (TCR) genes are assembled during
      lymphocyte maturation through site-specific V(D)J recombination events. Here we
      show that E2A proteins act in concert with RAG1 and RAG2 to activate Ig VK1J but
      not Iglambda VlambdaIII-Jlambda1 rearrangement in an embryonic kidney cell line.
      In contrast, EBF, but not E2A, promotes VlambdaIII-Jlambda1 recombination. Either
      E2A or EBF activate IgH DH4J recombination but not V(D)J rearrangement. The Ig
      coding joints are diverse, contain nucleotide deletions, and lack N nucleotide
      additions. IgK VJ recombination requires the presence of the E2A transactivation
      domains. These observations indicate that in nonlymphoid cells a diverse Ig
      repertoire can be generated by the mere expression of the V(D)J recombinase and a
      transcriptional regulator.

PMID- 10882076
TI  - The ISWI chromatin-remodeling protein is required for gene expression and the
      maintenance of higher order chromatin structure in vivo.
AB  - Drosophila ISWI, a highly conserved member of the SWI2/SNF2 family of ATPases, is
      the catalytic subunit of three chromatin-remodeling complexes: NURF, CHRAC, and
      ACF. To clarify the biological functions of ISWI, we generated and characterized
      null and dominant-negative ISWI mutations. We found that ISWI mutations affect
      both cell viability and gene expression during Drosophila development. ISWI
      mutations also cause striking alterations in the structure of the male X
      chromosome. The ISWI protein does not colocalize with RNA Pol II on salivary
      gland polytene chromosomes, suggesting a possible role for ISWI in
      transcriptional repression. These findings reveal novel functions for the ISWI
      ATPase and underscore its importance in chromatin remodeling in vivo.

PMID- 10882077
TI  - Activation of transcription through histone H4 acetylation by MOF, an
      acetyltransferase essential for dosage compensation in Drosophila.
AB  - Dosage compensation in Drosophila involves a 2-fold increase in transcription
      from the single male X relative to the two female X chromosomes. Regulation at
      the level of the chromosome involves alterations in chromatin organization: male
      X chromosomes appear decondensed and are marked by acetylation of histone H4 at
      lysine 16. We demonstrate that MOF, a protein required for dosage compensation
      with significant sequence similarity to the MYST family of acetyltransferases, is
      a histone acetyltransferase that acetylates chromatin specifically at histone H4
      lysine 16. This acetylation relieves chromatin-mediated repression of
      transcription in vitro and in vivo if MOF is targeted to a promoter by fusion to
      a DNA-binding domain. Acetylation of chromatin by MOF, therefore, appears to be
      causally involved in transcriptional activation during dosage compensation.

PMID- 10882078
TI  - Intergenic transcription and developmental remodeling of chromatin subdomains in
      the human beta-globin locus.
AB  - Gene activation requires chromatin remodeling complexes, which hyperacetylate
      histones and enable factor access; however, the targeting mechanisms leading to
      the establishment and maintenance of large, hyperacetylated DNase-sensitive
      chromatin domains are unknown. Recent work has shown that histone
      acetyltransferases are associated with RNA-pol II complexes, suggesting that
      transcription of chromatin plays a role in chromatin modification. Here we show
      the human beta-globin locus is divided into three differentially activated
      chromatin subdomains. Large transcripts precisely delineate the active domains at
      key cell cycle points associated with chromatin transitions and remodeling. We
      identify an element that initiates these transcripts, located in a region
      required for chromatin activation. The results suggest that intergenic
      transcription is required for chromatin remodeling of chromosomal domains.

PMID- 10882079
TI  - Beta-globin gene switching and DNase I sensitivity of the endogenous beta-globin
      locus in mice do not require the locus control region.
AB  - We have generated mice with a targeted deletion of the beta-globin locus control
      region (LCR). Mice homozygous for the deletion die early in embryogenesis but can
      be rescued with a YAC containing the human beta-globin locus. After germline
      passage, deletion of the LCR leads to a severe reduction in expression of all
      mouse beta-like globin genes, but no alteration in the developmental specificity
      of expression. Furthermore, a DNase I-sensitive "open" chromatin conformation of
      the locus is established and maintained. Thus, the dominant role of the LCR in
      the native locus is to confer high-level transcription, and elements elsewhere in
      the locus are sufficient to establish and maintain an open conformation and to
      confer developmentally regulated globin gene expression.

PMID- 10882080
TI  - Homeodomain position 54 specifies transcriptional versus translational control by
      Bicoid.
AB  - Bicoid (BCD), the anterior determinant of Drosophila, controls embryonic gene
      expression by transcriptional activation and translational repression. Both
      functions require the homeodomain (HD), which recognizes DNA motifs at target
      gene enhancers and a specific sequence interval in the 3' untranslated region of
      caudal (cad) mRNA. Here we show that the BCD HD is a nucleic acid-binding unit.
      Its helix III contains an arginine-rich motif (ARM), similar to the RNA-binding
      domain of the HIV-1 protein REV, needed for both RNA and DNA recognition.
      Replacement of arginine 54, within this motif, alters the RNA but not the DNA
      binding properties of the HD. Corresponding BCD mutants fail to repress cad mRNA
      translation, whereas the transcriptional target genes are still activated.

PMID- 10882081
TI  - Proteasomal turnover of p21Cip1 does not require p21Cip1 ubiquitination.
AB  - The Cdk inhibitor p21Cip1 is an unstable protein. Pharmacologic inhibition of the
      proteasome increases the half-life of p21 from less than 30 min to more than 2 hr
      and results in the accumulation of p21-ubiquitin conjugates. To determine whether
      ubiquitination was required for proteasomal degradation of p21, we constructed
      mutant versions of p21 that were not ubiquitinated in vivo. Remarkably, these
      mutants remained unstable and increased in abundance upon proteasome inhibition,
      indicating that direct ubiquitination of p21 is not necessary for its turnover by
      the proteasome. The frequently observed correlation between protein
      ubiquitination and proteasomal degradation is insufficient to conclude that
      ubiquitination is a prerequisite for degradation.

PMID- 10882082
TI  - Shigella and Escherichia coli at the crossroads: machiavellian masqueraders or
      taxonomic treachery?

PMID- 10882083
TI  - Hantaviruses.
AB  - Since the recognition of the hantavirus pulmonary syndrome (HPS) in the USA in
      1993, interest in hantavirus diseases has intensified worldwide. It is clear that
      hantaviruses have been historically responsible for a variety of human illnesses.
      Hantaviruses form a separate genus within the Bunyaviridae family. There are
      currently >20 recognised sero/genotypes and many others are under investigation.
      Each hantavirus type appears to be specific to a different rodent host. Virus
      phylogeny very closely reflects rodent phylogeny. The different hantavirus types
      are associated with different types of disease both in terms of target organs and
      disease severity. Two major diseases are recognised: haemorrhagic fever with
      renal syndrome (HFRS) and HPS. HFRS is primarily a disease of the old world while
      HPS is only recognised in the Americas. Over the past few decades the
      understanding and recognition of hantavirus disease throughout the world have
      greatly expanded. The number of recognised virus types continues to grow, as does
      the spectrum of hantavirus disease. There is evidence of hantavirus causing human
      disease in the British Isles, but at present it remains a largely uncharacterised
      disease.

PMID- 10882084
TI  - Amphotericin B resistance of Aspergillus terreus in a murine model of
      disseminated aspergillosis.
AB  - The in-vivo activity of amphotericin B and itraconazole against a clinical
      isolate of Aspergillus terreus was determined in a murine model of disseminated
      aspergillosis. MICs of amphotericin B and itraconazole for the strain, determined
      by an NCCLS-based technique, were 2 microg/ml and 1 microg/ml, respectively. Mice
      infected intravenously were treated with either itraconazole (50 or 100
      mg/kg/day) or amphotericin B 4.5 mg/kg/day for 10 days. Treatment with both doses
      of itraconazole significantly prolonged the survival rates compared with those
      for untreated mice. In comparison, mortality rate and median survival time were
      identical for mice treated with amphotericin B and for mice given no therapy,
      indicating that the strain was highly resistant to amphotericin B in this model.
      Analysis of sterol composition showed that the major sterol was ergosterol. This
      suggests that amphotericin B resistance was not related to a modified sterol
      profile.

PMID- 10882085
TI  - Secretion of the chemokine interleukin-8 during Japanese encephalitis virus
      infection.
AB  - Japanese encephalitis (JE) virus infection induces infiltration of neutrophils in
      neural as well as extraneural tissues in patients. As interleukin-8 (IL-8) has
      inflammatory properties, the present study was undertaken to investigate the IL-8
      concentrations in cerebrospinal fluid (CSF) and serum from patients with JE and
      correlate them with neutrophil counts. IL-8 was measured in the CSF or serum of
      30 patients with confirmed JE. The majority (92%) of the acute CSF samples showed
      raised levels of IL-8 with raised numbers of polymorphonuclear leucocytes.
      Similarly, significantly higher serum IL-8 concentrations were detected in the
      acute phase of illness than in convalescent JE patients or normal healthy
      controls. Twenty-one of 25 patients with high concentrations of IL-8 showed
      significantly increased neutrophil counts in acute phase sera. A gradual decline
      in neutrophil counts was observed in the convalescent phase of patients who
      recovered. There was a significant correlation between IL-8 level and the
      severity of illness, as all severely ill and fatal cases showed higher levels of
      IL-8 in acute CSF or serum than the levels found in those who recovered. IL-8
      concentrations remained high for a longer period in patients with prolonged
      severe illness than in those who made a complete recovery.

PMID- 10882086
TI  - A potential role for tumour necrosis factor-alpha in synergy between porcine
      respiratory coronavirus and bacterial lipopolysaccharide in the induction of
      respiratory disease in pigs.
AB  - This study examined whether exposure of pigs to both porcine respiratory
      coronavirus (PRCV) and bacterial lipopolysaccharide (LPS) can potentiate
      respiratory disease and lung secretion of tumour necrosis factor-a (TNF-alpha)
      and interleukin-1 (IL-1). Caesarian-derived colostrum-deprived pigs were
      inoculated intratracheally with PRCV, with LPS from Escherichia coli O111:B4 (20
      microg/kg), or with a combination of the two, and killed at set times after
      inoculation. Clinical signs, virus replication and (histo)pathological changes in
      the lungs, percentage of neutrophils and bioactive TNF-alpha and IL-1 in broncho
      alveolar lavage (BAL) fluids were examined. The effects of separate virus or LPS
      inoculations were subclinical and failed to induce high and sustained cytokine
      levels. In a preliminary study, pigs were inoculated with PRCV and then with LPS
      24 h later and killed sequentially. Severe respiratory disease and significantly
      enhanced TNF-alpha titres (208-3601 U/ml versus 40-89 U/ml after LPS only) were
      seen during the first 12 h after LPS inoculation. IL-1 levels (106-1631 U/ml
      versus 28-654 U/ml after LPS only) were also increased, but persisted for longer
      after clinical recovery than TNF-alpha. In a second study, pigs were inoculated
      with PRCV and subsequently with LPS at various time intervals ranging from 0 to
      24 h, and killed 5 h after inoculation with LPS. A time interval of at least 12 h
      between inoculations was necessary for prominent respiratory signs to develop.
      Production of TNF-alpha, but not IL-1, was also dependent on the time interval
      between inoculations and was tightly correlated with disease. Lung neutrophil
      infiltration and pathological changes were comparable after combined PRCV-LPS and
      single LPS inoculations, and were not associated with disease. These data show
      that exposure to high endotoxin concentrations in swine buildings can precipitate
      respiratory disease in PRCV-infected pigs, and that TNF-alpha is probably an
      important mediator of these effects. This is the first in-vivo demonstration of
      synergy between respiratory viruses and LPS.

PMID- 10882087
TI  - Expression of trypsin-like activity by the genera Corynebacterium and Actinomyces
      in canine periodontitis.
AB  - Trypsin-like activity (TLA), clinical parameters and TLA-positive bacteria were
      examined in periodontitis and healthy sites in dogs. TLA was markedly higher in
      periodontitis than at healthy sites. There was good correlation between TLA
      positivity and severity of periodontal disease. The proportions of TLA-positive
      bacteria to total isolates in periodontitis and healthy sites were 21.1% and
      2.1%, respectively. Among TLA-positive bacteria in periodontitis sites, 4.4%
      showed strong TLA activity, 35.3% showed moderate and 60.3% showed weak activity.
      In the healthy sites, all the TLA-positive bacteria showed weak activity. In all,
      90% of the total number of TLA-positive bacteria were identified as belonging to
      the family Actinomycetaceae; 40% of bacteria belonging to the family
      Actinomycetaceae were identified as genus Corynebacterium with moderate trypsin
      like activity and the remaining 60% were identified as genus Actinomyces with
      weak activity. Obligately anaerobic bacteria accounted for only 5.9% of the total
      population of TLA-positive bacteria; they were gram-negative coccobacilli, gram
      positive rods and gram-positive cocci. These observations suggested that bacteria
      in the family Actinomycetaceae may play an important role in periodontitis and
      that measurement of TLA is a clinically reliable marker for the diagnosis of
      periodontitis in dogs.

PMID- 10882088
TI  - Increased gastric emptying induced by Helicobacter heilmannii type 1 infection in
      rats.
AB  - The association between Helicobacter pylori infection and gastric motility
      abnormalities is still controversial, partly because of the lack of an
      appropriate animal model. H. heilmannii type 1 (Hh1), a spiral bacterium that
      infects the stomach of both man and pigs, easily colonises and induces an
      inflammatory response in the gastric mucosa of rodents. For these reasons, the
      present study investigated the relationship between gastric motility in rats
      experimentally infected with Hh1 and correlated the results with serum gastrin
      and gastric somatostatin concentrations, as these hormones seem to be involved in
      gastric motility. Ten rats were inoculated with gastric mucus from an Hh1
      positive pig and 10 animals with gastric mucus from an Hh1-negative pig (control
      group). After 56 days, gastric emptying was studied in vivo by scintigraphy. The
      animals were then killed, blood samples were collected for serum gastrin
      measurement, strips of the gastric wall were obtained for an in-vitro motor study
      and fragments of the gastric antrum were obtained for somatostatin content
      evaluation, Hh1 diagnosis and histological study. There was a significant
      increase in gastric emptying in the test group compared with the controls as
      demonstrated by the in-vivo and in-vitro studies. Serum gastrin levels were
      significantly higher and somatostatin levels were lower in the test group than in
      the controls. In addition, infected animals showed evidence of gastritis on
      histological examination. Gastric motility is altered in rats infected with Hh1,
      a fact possibly related to concurrent abnormalities of gastrin and somatostatin
      secretion.

PMID- 10882089
TI  - Studies of the effect of Clostridium butyricum on Helicobacter pylori in several
      test models including gnotobiotic mice.
AB  - The interaction between Clostridium butyricum and Helicobacter pylori was
      examined in vitro and in vivo. The culture supernate of C. butyricum MIYAIRI 588
      inhibited the growth of H. pylori even when its pH was adjusted to 7.4. The
      bactericidal effect of butyric acid on H. pylori was stronger than that of
      lactic, acetic or hydrochloric acids. Flow cytometric analysis showed that pre
      incubation of gastric epithelial (MKN45) cells with H. pylori and C. butyricum
      inhibited the adhesion of H. pylori to the cells. Persistent infection with H.
      pylori in the gastric mucosa of germ-free mice was observed for 5 weeks. Cure of
      persistent infection with H. pylori in the gnotobiotic mice was demonstrated
      following infection with C. butyricum. The probiotic agent, C. butyricum MIYAIRI
      588 may have some beneficial effects on H. pylori infection.

PMID- 10882090
TI  - Identification of an immunogenic 18-kDa protein of Helicobacter pylori by
      alkaline phosphatase gene fusions.
AB  - The use of alkaline phosphatase fusion methodology to identify Helicobacter
      pylori exported proteins enabled the identification of an open reading frame
      (ORF) encoding a highly immunogenic, previously uncharacterised exported protein.
      The predicted aminoacid sequence displays a typical N-terminal signal peptide and
      contains regions of C-terminal hydrophobicity consistent with a membrane
      associated protein. Southern blot analysis revealed that the gene encoding the
      protein was absent in several Helicobacter spp. and a combination of PCR and
      sequence analysis of the amplified gene showed that it is highly conserved
      amongst isolates of H. pylori. To obtain pure recombinant protein, the gene
      encoding the protein was cloned and expressed as a beta-galactosidase (beta-gal)
      fusion in Escherichia coli and the protein was purified by affinity
      chromatography and proteolytic cleavage of the beta-gal portion. The purified
      protein, which has an apparent mol. wt of 18 kDa, was recognised by antibody
      present in 71% of sera from patients infected with H. pylori, but in only 16% of
      sera from patients with unrelated or no gastrointestinal disease, by Western blot
      assays. These results indicate that the 18-kDa protein from H. pylori is
      immunogenic and is expressed in vivo.

PMID- 10882091
TI  - Simultaneous identification and typing of multi-drug-resistant Mycobacterium
      tuberculosis isolates by analysis of pncA and rpoB.
AB  - In Mycobacterium tuberculosis there is a strong correlation between in-vitro
      resistance to rifampicin (RIF) and pyrazinamide (PZA) and mutations in rpoB and
      pncA, respectively. Approximately 50 mutations associated with resistance have
      been reported for rpoB and 70 for pncA, and, theoretically, many more are
      possible. Therefore, the identification of rpoB and pncA mutations in M.
      tuberculosis might be used for the simultaneous determination of resistance and
      for typing multi-drug-resistant (MDR) strains during possible outbreaks. The
      present study examined four sensitive and six MDR isolates of M. tuberculosis
      from Turkey and eight isolates from a nosocomial MDR tuberculosis (TB) outbreak
      in the UK. Gene mutations were identified by the Innogenetics LiPA rpoB assay or
      automated sequencing, or both. All the sensitive isolates had rpoB and pncA wild
      type genotypes, whereas all the RIF- and PZA-resistant isolates had rpoB and pncA
      mutations. All four mutations seen in rpoB, but none of the six in pncA, had been
      reported previously. The rpoB and pncA mutations seen in the Turkish isolates
      defined six distinct genotypes amongst the six MDR isolates, while standard
      IS6110 typing discriminated only four. All isolates from the single strain MDR-TB
      outbreak had identical genotypes. Rapid genotyping was performed on the sputum
      from a patient who presented 2 years after the initial MDR-TB outbreak and this
      showed rpoB and pncA genotypes identical to the other outbreak isolates. This
      result was available within 36 h. The analysis of rpoB and pncA is a rapid and
      practical means of simultaneously identifying and typing MDR isolates of M.
      tuberculosis.

PMID- 10882092
TI  - Molecular cloning of a gene (poIA) coding for an unusual DNA polymerase I from
      Treponema pallidum.
AB  - The gene coding for the DNA polymerase I from Treponema pallidum, Nichols strain,
      was cloned and sequenced. Depending on which of the two alternative initiation
      codons was used, the protein was either 997 or 1015 amino acids long and the
      predicted protein had a molecular mass of either 112 or 114 kDa. Sequence
      comparisons with other polA genes showed that all three domains expected in the
      DNA polymerase I class of enzymes were present in the protein (5'-3' exonuclease,
      3'-5' exonuclease and polymerase domains). Additionally, there were four unique
      insertions of 20-30 amino acids each, not seen in other DNA polymerase I enzymes.
      Two of the inserts were near the boundary of the two exonuclease domains and the
      other two interrupted the 3'-5' exonuclease domain which is involved in
      proofreading. The predicted amino-acid sequence had an exceptionally high content
      of cysteine (2.4% compared with <0.05% for most other sequenced DNA polymerase I
      enzymes). The polA gene was further cloned into pProEXHTa for expression and
      purification. The transformants expressed a protein of 115 kDa. Antibodies raised
      against synthetic peptide fragments of the putative DNA polymerase I recognised
      the 115-kda band in Western blot analysis. No DNA synthesis activity could be
      demonstrated on a primed single-stranded template. Although significant
      quantities of the protein were produced in the host Escherichia coli carrying the
      plasmid, it was not capable of complementing a polA(-) mutant in the replication
      of a polA-dependent plasmid.

PMID- 10882093
TI  - Detection and characterisation of the genes encoding glyoxalase I and II from
      Neisseria meningitidis.
AB  - Glyoxalase enzymes I and II are involved in a detoxification process consisting
      of conversion of reactive dicarbonyl compounds (e.g., methylglyoxal) to less
      reactive hydroxy acids. The structural gene for meningococcal glyoxalase I (gloA)
      was identified by screening an expression library with a rabbit antiserum. The
      meningococcal gloA gene consisted of 138 deduced amino acids, with a calculated
      mol. wt of 15.7 kDa. The DNA and deduced protein sequence of gloA was compared to
      known sequences of glyoxalase I enzymes and showed high homology with gloA of
      several eukaryotic and prokaryotic species. Insertion of a gloA-containing
      plasmid in Escherichia coli increased the host organism's tolerance to
      methylglyoxal from <2 mM to >4 mM, thus demonstrating its functional identity. A
      databank search also revealed the presence of a putative gloB gene, encoding
      glyoxalase II (GlxII), in the recently released genomic sequences of Neisseria
      meningitidis and N. gonorrhoeae.

PMID- 10882094
TI  - Differentiation of non-pathogenic (biotype 1A) Yersinia enterocolitica from
      pathogenic bioserotypes by sodium acetate utilisation.

PMID- 10882095
TI  - Antimicrobial activity of nicotine against a spectrum of bacterial and fungal
      pathogens.

PMID- 10882096
TI  - Identification and characterization of a novel cell cycle-regulated internal
      ribosome entry site.
AB  - PITSLRE protein kinases are related to the large family of cyclin-dependent
      kinases. They have been proposed to act as tumor suppressor genes and have been
      shown to play a role in cell cycle progression. We report that two PITSLRE
      protein kinase isoforms, namely p11O(PITSLRE) and p58(PITSLRE), are translated
      from a single transcript by initiation at alternative in-frame AUG codons.
      p110(PITSLRE) is produced by classical cap-dependent translation, whereas
      p58(PITSLRE) results from internal initiation of translation controlled by an
      internal ribosome entry site (IRES) with unique properties. The IRES element is
      localized to the mRNA coding region, and its activity is cell cycle regulated,
      which permits translation of p58(PITSLRE) in G2/M.

PMID- 10882097
TI  - A cell cycle-dependent internal ribosome entry site.
AB  - The eukaryotic mRNA 5' cap structure facilitates translation. However, cap
      dependent translation is impaired at mitosis, suggesting a cap-independent
      mechanism for mRNAs translated during mitosis. Translation of ornithine
      decarboxylase (ODC), the rate-limiting enzyme in the biosynthesis of polyamines,
      peaks twice during the cell cycle, at the G1/S transition and at G2/M. Here, we
      describe a cap-independent internal ribosome entry site (IRES) in the ODC mRNA
      that functions exclusively at G2/M. This ensures elevated levels of polyamines,
      which are implicated in mitotic spindle formation and chromatin condensation. c
      myc mRNA also contains an IRES that functions during mitosis. Thus, IRES
      dependent translation is likely to be a general mechanism to synthesize short
      lived proteins even at mitosis, when cap-dependent translation is interdicted.

PMID- 10882098
TI  - Initiation of eukaryotic DNA replication: origin unwinding and sequential
      chromatin association of Cdc45, RPA, and DNA polymerase alpha.
AB  - We report that a plasmid replicating in Xenopus egg extracts becomes negatively
      supercoiled during replication initiation. Supercoiling requires the initiation
      factor Cdc45, as well as the single-stranded DNA-binding protein RPA, and
      therefore likely represents origin unwinding. When unwinding is prevented, Cdc45
      binds to chromatin whereas DNA polymerase alpha does not, indicating that Cdc45,
      RPA, and DNA polymerase alpha bind chromatin sequentially at the G1/S transition.
      Whereas the extent of origin unwinding is normally limited, it increases
      dramatically when DNA polymerase alpha is inhibited, indicating that the helicase
      that unwinds DNA during initiation can become uncoupled from the replication
      fork. We discuss the implications of these results for the location of
      replication start sites relative to the prereplication complex.

PMID- 10882099
TI  - Membrane protein degradation by AAA proteases in mitochondria: extraction of
      substrates from either membrane surface.
AB  - Two AAA proteases, each with its catalytic site at the opposite membrane surface,
      mediate the ATP-dependent degradation of mitochondrial inner membrane proteins.
      We demonstrate here that a model substrate polypeptide containing hydrophilic
      domains at both sides of the membrane can be completely degraded by either of the
      AAA proteases, if solvent-exposed domains are in an unfolded state. A short
      protein tail protruding from the membrane surface is sufficient to allow the
      proteolytic attack of an AAA protease that facilitates domain unfolding at the
      opposite side. Our results provide a rationale for the membrane arrangement of
      AAA proteases in mitochondria and demonstrate that degradation of membrane
      proteins by AAA proteases involves an active extraction of transmembrane segments
      and transport of solvent-exposed domains across the membrane.

PMID- 10882100
TI  - Dynamics of substrate denaturation and translocation by the ClpXP degradation
      machine.
AB  - ClpXP is a protein machine composed of the ClpX ATPase, a member of the
      Clp/Hsp100 family of remodeling enzymes, and the ClpP peptidase. Here, ClpX and
      ClpXP are shown to catalyze denaturation of GFP modified with an ssrA degradation
      tag. ClpX translocates this denatured protein into the proteolytic chamber of
      ClpP and, when proteolysis is blocked, also catalyzes release of denatured GFP
      ssrA from ClpP in a reaction that requires ATP and additional substrate. Kinetic
      experiments reveal that multiple reaction steps require collaboration between
      ClpX and ClpP and that denaturation is the rate-determining step in degradation.
      These insights into the mechanism of ClpXP explain how it executes efficient
      degradation in a manner that is highly specific for tagged proteins, irrespective
      of their intrinsic stabilities.

PMID- 10882101
TI  - TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1
      to TRAF6 in the IL-1 signal transduction pathway.
AB  - The TAK1 MAPKKK mediates activation of JNK and NF-KB in the IL-1-activated
      signaling pathway. Here we report the identification of TAB2, a novel
      intermediate in the IL-1 pathway that functionally links TAK1 to TRAF6.
      Expression of TAB2 induces JNK and NF-kappaB activation, whereas a dominant
      negative mutant TAB2 impairs their activation by IL-1. IL-1 stimulates
      translocation of TAB2 from the membrane to the cytosol where it mediates the IL-1
      dependent association of TAK1 with TRAF6. These results define TAB2 as an adaptor
      linking TAK1 and TRAF6 and as a mediator of TAK1 activation in the IL-1 signaling
      pathway.

PMID- 10882102
TI  - The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let
      7 regulatory RNA and the LIN-29 transcription factor.
AB  - Null mutations in the C. elegans heterochronic gene lin-41 cause precocious
      expression of adult fates at larval stages. Increased lin-41 activity causes the
      opposite phenotype, reiteration of larval fates. let-7 mutations cause similar
      reiterated heterochronic phenotypes that are suppressed by lin-41 mutations,
      showing that lin-41 is negatively regulated by let-7. lin-41 negatively regulates
      the timing of LIN-29 adult specification transcription factor expression. lin-41
      encodes an RBCC protein, and two elements in the lin-413'UTR are complementary to
      the 21 nucleotide let-7 regulatory RNA. A lin-41::GFP fusion gene is
      downregulated in the tissues affected by lin-41 at the time that the let-7
      regulatory RNA is upregulated. We suggest that late larval activation of let-7
      RNA expression downregulates LIN-41 to relieve inhibition of lin-29.

PMID- 10882103
TI  - MEX-5 and MEX-6 function to establish soma/germline asymmetry in early C. elegans
      embryos.
AB  - An asymmetrical network of cortically localized PAR proteins forms shortly after
      fertilization of the C. elegans egg. This network is required for subsequent
      asymmetries in the expression patterns of several proteins that are encoded by
      nonlocalized, maternally expressed mRNAs. We provide evidence that two nearly
      identical genes, mex-5 and mex-6, link PAR asymmetry to those subsequent protein
      asymmetries. MEX-5 is a novel, cytoplasmic protein that is localized through PAR
      activities to the anterior pole of the 1-cell stage embryo. MEX-5 localization is
      reciprocal to that of a group of posterior-localized proteins called germline
      proteins. Ectopic expression of MEX-5 is sufficient to inhibit the expression of
      germline proteins, suggesting that MEX-5 functions to inhibit anterior expression
      of the germline proteins.

PMID- 10882104
TI  - Involvement of the TRAP220 component of the TRAP/SMCC coactivator complex in
      embryonic development and thyroid hormone action.
AB  - The TRAP220 component of the TRAP/SMCC complex, a mammalian homologof the yeast
      Mediator that shows diverse coactivation functions, interacts directly with
      nuclear receptors. Ablation of the murine Trap220 gene revealed that null mutants
      die during an early gestational stage with heart failure and exhibit impaired
      neuronal development with extensive apoptosis. Primary embryonic fibroblasts
      derived from null mutants show an impaired cell cycle regulation and a prominent
      decrease of thyroid hormone receptor function that is restored by ectopic TRAP220
      but no defect in activation by Gal4-RARalpha/RXRalpha, p53, or VP16. Moreover,
      haploinsufficient animals show growth retardation, pituitary hypothyroidism, and
      widely impaired transcription in certain organs. These results indicate that
      TRAP220 is essential for a wide range of physiological processes but also that it
      has gene- and activator-selective functions.

PMID- 10882105
TI  - A shift from reversible to irreversible X inactivation is triggered during ES
      cell differentiation.
AB  - Xist is required for X inactivation. To study the initiation of X inactivation,
      we have generated a full-length mouse Xist cDNA transgene and an inducible
      expression system facilitating controlled Xist expression in ES cells and
      differentiated cultures. In ES cells, transgenic Xist RNA was stable and caused
      long-range transcriptional repression in cis. Repression was reversible and
      dependent on continued Xist expression in ES cells and early ES cell
      differentiation. By 72 hr of differentiation, inactivation became irreversible
      and independent of Xist. Upon differentiation, autosomal transgenes did not
      effect counting, but transgenic Xist RNA induced late replication and histone H4
      hypoacetylation. Xist had to be activated within 48 hr of differentiation to
      effect silencing, suggesting that reversible repression by Xist is a required
      initiation step that might occur during normal X inactivation in female cells.

PMID- 10882106
TI  - M6P/IGF2R imprinting evolution in mammals.
AB  - Imprinted gene identification in animals has been limited to eutherian mammals,
      suggesting a significant role for intrauterine fetal development in the evolution
      of imprinting. We report herein that M6P/IGF2R is not imprinted in monotremes and
      does not encode for a receptor that binds IGF2. In contrast, M6P/IGF2R is
      imprinted in a didelphid marsupial, the opossum, but it strikingly lacks the
      differentially methylated CpG island in intron 2 postulated to be involved in
      imprint control. Thus, invasive placentation and gestational fetal growth are not
      required for imprinted genes to evolve. Unless there was convergent evolution of
      M6P/ IGF2R imprinting and receptor IGF2 binding in marsupials and eutherians, our
      results also demonstrate that these two functions evolved in a mammalian clade
      exclusive of monotremes.

PMID- 10882107
TI  - A novel mycolic acid cyclopropane synthetase is required for cording,
      persistence, and virulence of Mycobacterium tuberculosis.
AB  - Colonial morphology of pathogenic bacteria is often associated with virulence.
      For M. tuberculosis, the causative agent of tuberculosis (TB), virulence is
      correlated with the formation of serpentine cords, a morphology that was first
      noted by Koch. We identified a mycobacterial gene, pcaA, that we show is required
      for cording and mycolic acid cyclopropane ring synthesis in the cell wall of both
      BCG and M. tuberculosis. Furthermore, we show that mutants of pcaA fail to
      persist within and kill infected mice despite normal initial replication. These
      results indicate that a novel member of a family of cyclopropane synthetases is
      necessary for lethal chronic persistent M. tuberculosis infection and define a
      role for cyclopropanated lipids in bacterial pathogenesis.

PMID- 10882108
TI  - Degradation of proteins from the ER of S. cerevisiae requires an intact unfolded
      protein response pathway.
AB  - To dissect the requirements of membrane protein degradation from the ER, we
      expressed the mouse major histocompatibility complex class I heavy chain H-2K(b)
      in yeast. Like other proteins degraded from the ER, unassembled H-2K(b) heavy
      chains are not transported to the Golgi but are degraded in a proteasome
      dependent manner. The overexpression of H-2K(b) heavy chains induces the unfolded
      protein response (UPR). In yeast mutants unable to mount the UPR, H-2K(b) heavy
      chains are greatly stabilized. This defect in degradation is suppressed by the
      expression of the active form of Hac1p, the transcription factor that upregulates
      UPR-induced genes. These results indicate that induction of the UPR is required
      for the degradation of protein substrates from the ER.

PMID- 10882110
TI  - Acetylation regulates transcription factor activity at multiple levels.
AB  - CREB-binding protein (CBP) possesses an intrinsic acetyltransferase activity
      capable of acetylating nucleosomal histones as well as several nonhistone
      proteins. Here, it is shown that CBP can acetylate hepatocyte nuclear factor-4
      (HNF-4), a member of the nuclear hormone receptor family, at lysine residues
      within the nuclear localization sequence. CBP-mediated acetylation is crucial for
      the proper nuclear retention of HNF-4, which is otherwise transported out to the
      cytoplasm via the CRM1 pathway. Acetylation also increases HNF-4 DNA binding
      activity and its affinity of interaction with CBP itself and is required for
      target gene activation. The results show that acetylation is a key
      posttranslational modification that may affect several properties of a
      transcription factor critical for the execution of its biological functions.

PMID- 10882109
TI  - Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV
      induced mutagenesis.
AB  - UV-damaged DNA-binding activity (UV-DDB) is deficient in some xeroderma
      pigmentosum group E individuals due to mutation of the p48 gene, but its role in
      DNA repair has been obscure. We found that UV-DDB is also deficient in cell lines
      and primary tissues from rodents. Transfection of p48 conferred UV-DDB to hamster
      cells, and enhanced removal of cyclobutane pyrimidine dimers (CPDs) from genomic
      DNA and from the nontranscribed strand of an expressed gene. Expression of p48
      suppressed UV-induced mutations arising from the nontranscribed strand, but had
      no effect on cellular UV sensitivity. These results define the role of p48 in DNA
      repair, demonstrate the importance of CPDs in mutagenesis, and suggest how rodent
      models can be improved to better reflect cancer susceptibility in humans.

PMID- 10882111
TI  - The USA-derived transcriptional coactivator PC2 is a submodule of TRAP/SMCC and
      acts synergistically with other PCs.
AB  - PC2, the high-molecular weight constituent of the potent USA transcriptional
      coactivator fraction, was identified as a Mediator-like complex. Its composition
      resembles that of the TRAP/SMCC complex, but PC2 is distinguished by the
      prominent absence of the SRB10 and SRB11 kinase/cyclin pair, as well as several
      additional polypeptides. Furthermore, affinity-purified PC2, which lacks
      independent activity, acts in synergy with USA-derived coactivators
      PC3/topoisomerase I and PC4 to mediate the effects of a variety of activators
      (including VP16, the synthetic activator GAL4-AH, and the orphan nuclear receptor
      HNF4) and thus recapitulates partial USA coactivator function.

PMID- 10882112
TI  - Multiple functions of an evolutionarily conserved RNA binding domain.
AB  - Ribosomal protein L30 of Saccharomyces cerevisiae binds to a distinct RNA
      structure to inhibit the splicing and the translation of its own transcript.
      Remarkably, the ortholog of L30 from the archaeon Sulfolobus acidocaldarius binds
      specifically to the same RNA fragment and inhibits splicing both in vitro and in
      vivo. Indeed, expression of Sulfolobus L30 in yeast severely reduces growth by
      limiting production of the endogenous L30. This conservation of binding
      specificity implies that the target of regulation in the RPL30 transcript mimics
      a site in the rRNA that has been conserved for more than a billion years. We
      identify this site, whose location suggests that L30, which has no apparent
      eubacterial ortholog, is responsible for establishing the orientation of a key
      bridge between the large and small ribosomal subunits.

PMID- 10882113
TI  - Replication of yeast rDNA initiates downstream of transcriptionally active genes.
AB  - In the yeast S. cerevisiae, ARS (autonomously replicating sequence) elements
      located in the intergenic spacers of the rRNA gene locus are infrequently
      activated as origins of replication. We analyzed the rARS activation with a
      combination of neutral/neutral (N/N) two-dimensional (2D) gel electrophoresis and
      either the intercalating drug psoralen, which in vivo specifically marks the
      transcribing gene copies, or the selective accessibility of restriction sites in
      transcriptionally active genes. We found that initiation of replication starts at
      those rARSs placed immediately downstream of transcribing rRNA genes. This
      correlation between transcription and replication is consistent with the presence
      of nucleosome-free enhancers at each transcriptionally active gene copy and
      suggests that the transcription factor Abf1p is involved in replication
      initiation at the ARS in the rDNA gene locus.

PMID- 10882114
TI  - Functional association of U2 snRNP with the ATP-independent spliceosomal complex
      E.
AB  - In the current model for spliceosome assembly, U1 snRNP binds to the 5' splice
      site in the E complex followed by ATP-dependent binding of U2 snRNP to the
      branchpoint sequence (BPS) in the A complex. Here we report the characterization
      of highly purified, functional E complex. We provide evidence that this complex
      contains functional U2 snRNP and that this snRNP is required for E complex
      assembly. The BPS is not required for U2 snRNP binding in the E complex. These
      data suggest a model for spliceosome assembly in which U1 and U2 snRNPs first
      associate with the spliceosome in the E complex and then an ATP-dependent step
      results in highly stable U2 snRNP binding to the BPS in the A complex.

PMID- 10882115
TI  - The Saccharomyces cerevisiae Msh2 mismatch repair protein localizes to
      recombination intermediates in vivo.
AB  - Mismatch repair proteins act during double-strand break repair (DSBR) to correct
      mismatches in heteroduplex DNA, to suppress recombination between divergent
      sequences, and to promote removal of nonhomologous DNA at DSB ends. We
      investigated yeast Msh2p association with recombination intermediates in vivo
      using chromatin immunoprecipitation. During DSBR involving nonhomologous ends,
      Msh2p localized strongly to recipient and donor sequences. Localization required
      Msh3p and was greatly reduced in rad50delta strains. Minimal localization of
      Msh2p was observed during fully homologous repair, but this was increased in
      rad52delta strains. These findings argue that Msh2p-Msh3p associates with
      intermediates early in DSBR to participate in the rejection of homeologous
      pairing and to stabilize nonhomologous tails for cleavage by Rad1p-Rad10p
      endonuclease.

PMID- 10882116
TI  - Activation of p53 or loss of the Cockayne syndrome group B repair protein causes
      metaphase fragility of human U1, U2, and 5S genes.
AB  - Infection by adenovirus 12, transfection with the Ad12 E1B 55 kDa gene, or
      activation of p53 cause metaphase fragility of four loci (RNU1, PSU1, RNU2, and
      RN5S) each containing tandemly repeated genes for an abundant small RNA (U1, U2,
      and 5S RNA). We now show that loss of the Cockayne syndrome group B protein (CSB)
      or overexpression of the p53 carboxy-terminal domain induces fragility of the
      same loci; moreover, p53 interacts with CSB in vivo and in vitro. We propose that
      CSB functions as an elongation factor for transcription of structured RNAs,
      including some mRNAs. Activation of p53 would inhibit CSB, stalling transcription
      complexes and locally blocking chromatin condensation. Impaired transcription
      elongation may also explain the diverse clinical features of Cockayne syndrome.

PMID- 10882118
TI  - Acquisition of oncogenic potential by RAR chimeras in acute promyelocytic
      leukemia through formation of homodimers.
AB  - The t(15;17) chromosomal translocation in acute promyelocytic leukemia (APL)
      generates the PML-RARalpha fusion protein. The recruitment of nuclear receptor
      corepressor SMRT/N-CoR and subsequent repression of retinoid target genes is
      critical for the oncogenic function of PML-RARalpha. Here we show that the
      ability of PML-RARalpha to form homodimers is both necessary and sufficient for
      its increased binding efficiency to corepressor and inhibitory effects on
      hormonal responses in myeloid differentiation. We further provide evidence that
      altered stoichiometric interaction of SMRT with PML-RARalpha homodimers may
      underlie these processes. Finally, we demonstrate that a RXR AF2 mutant
      recapitulates many biochemical and functional properties of PML-RARalpha. Taken
      together, our results provide an example that altered dimerization of a
      transcription factor can be directly linked to cellular transformation and
      implicate dimerization interfaces of oncogenes as potential drug targets.

PMID- 10882117
TI  - Oligomerization of RAR and AML1 transcription factors as a novel mechanism of
      oncogenic activation.
AB  - RAR and AML1 transcription factors are found in leukemias as fusion proteins with
      PML and ETO, respectively. Association of PML-RAR and AML1-ETO with the nuclear
      corepressor (N-CoR)/histone deacetylase (HDAC) complex is required to block
      hematopoietic differentiation. We show that PML-RAR and AML1-ETO exist in vivo
      within high molecular weight (HMW) nuclear complexes, reflecting their oligomeric
      state. Oligomerization requires PML or ETO coiled-coil regions and is responsible
      for abnormal recruitment of N-CoR, transcriptional repression, and impaired
      differentiation of primary hematopoietic precursors. Fusion of RAR to a
      heterologous oligomerization domain recapitulated the properties of PML-RAR,
      indicating that oligomerization per se is sufficient to achieve transforming
      potential. These results show that oligomerization of a transcription factor,
      imposing an altered interaction with transcriptional coregulators, represents a
      novel mechanism of oncogenic activation.

PMID- 10882119
TI  - A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil
      extravasation by interacting with the FPR.
AB  - The glucocorticoid-regulated protein annexin I (lipocortin I) has been shown to
      mediate antiinflammatory activities of glucocorticoids, but the molecular basis
      of its action has remained elusive. Here we show that annexin I acts through the
      formyl peptide receptor (FPR) on human neutrophils. Peptides derived from the
      unique N-terminal domain of annexin I serve as FPR ligands and trigger different
      signaling pathways in a dose-dependent manner. Lower peptide concentrations
      possibly found in inflammatory situations elicit Ca2+ transients without fully
      activating the MAP kinase pathway. This causes a specific inhibition of the
      transendothelial migration of neutrophils and a desensitization of neutrophils
      toward a chemoattractant challenge. These findings identify annexin I peptides as
      novel, endogenous FPR ligands and establish a mechanistic basis of annexin I
      mediated antiinflammatory effects.

PMID- 10882120
TI  - Compartmentalization of the cell cortex by septins is required for maintenance of
      cell polarity in yeast.
AB  - Formation and maintenance of specialized plasma membrane domains are crucial for
      many biological processes, such as cell polarization and signaling. During
      isotropic bud growth, the yeast cell periphery is divided into two domains: the
      bud surface, an active site of exocytosis and growth, and the relatively
      quiescent surface of the mother cell. We found that cells lacking septins at the
      bud neck failed to maintain the exocytosis and morphogenesis factors Spa2, Sec3,
      Sec5, and Myo2 in the bud during isotropic growth. Furthermore, we found that
      septins were required for proper regulation of actin patch stability; septin
      defective cells permitted to enter isotropic growth lost actin and growth
      polarity. We propose that septins maintain cell polarity by specifying a boundary
      between cortical domains.

PMID- 10882121
TI  - G proteins mediate changes in cell shape by stabilizing the axis of polarity.
AB  - Upon exposure to mating pheromone, yeast cells change their form to pear-shaped
      shmoos. We looked at pheromone-dependent cell shape changes in mutants that are
      unable to orient growth during mating and unable to choose a bud site. In these
      double mutants, cell surface growth, secretion sites, cytoskeleton, and pheromone
      receptors are spread out, explaining why these cells are round. In contrast,
      polarity establishment proteins localize to discrete sites in these mutants.
      However, the location of these sites wanders. Thus, these mutants are able to
      initiate polarized growth but fail to maintain the location of growth sites. Our
      results demonstrate that stabilization of the growth axis requires positional
      signaling from either the pheromone receptor or specific bud site selection
      proteins.

PMID- 10882122
TI  - Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions
      and a regulatory element essential for cell growth in yeast.
AB  - Modification of cellular proteins by the ubiquitin-like protein SUMO is essential
      for nuclear processes and cell cycle progression in yeast. The Ulp1 protease
      catalyzes two essential functions in the SUMO pathway: (1) processing of full
      length SUMO to its mature form and (2) deconjugation of SUMO from targeted
      proteins. Selective reduction of the proteolytic reaction produced a covalent
      thiohemiacetal transition state complex between a Ulp1 C-terminal fragment and
      its cellular substrate Smt3, the yeast SUMO homolog. The Ulp1-Smt3 crystal
      structure and functional testing of elements within the conserved interface
      elucidate determinants of SUMO recognition, processing, and deconjugation.
      Genetic analysis guided by the structure further reveals a regulatory element N
      terminal to the proteolytic domain that is required for cell growth in yeast.

PMID- 10882123
TI  - Wnt/beta-catenin signaling induces the expression and activity of betaTrCP
      ubiquitin ligase receptor.
AB  - Beta-transducing repeat-containing protein (betaTrCP) targets the ubiquitination
      and subsequent degradation of both beta-catenin and IkappaB, thereby playing an
      important role in beta-catenin/Tcf and NF-kappaB-dependent signaling. Here
      evidence is presented that beta-catenin/Tcf signaling elevates the expression of
      betaTrCP mRNA and protein in a Tcf-dependent manner, which does not require
      betaTrCP transcription. Induction of betaTrCP expression by the beta-catenin/Tcf
      pathway results in an accelerated degradation of the wild-type beta-catenin,
      suggesting that the negative feedback loop regulation may control the beta
      catenin/Tcf pathway. This signaling also upregulated NF-kappaB transactivation
      without affecting the activity of IkappaB kinase, thereby establishing that the
      maintenance of the betaTrCP level is important for coordination between beta
      catenin/Tcf and NF-kappaB signaling.

PMID- 10882124
TI  - Meiotic DNA breaks associated with recombination in S. pombe.
AB  - In the fission yeast Schizosaccharomyces pombe, we have detected prominent DNA
      breaks that appeared shortly after premeiotic DNA replication. These breaks, like
      meiotic recombination, required the products of the six rec genes tested.
      Prominent breaks were detected at widely separated sites, about 100-300 kb apart,
      equivalent to about 50-150 sites per genome or approximately the number of
      meiotic recombination events. Certain features of these breaks are similar to
      those in the distantly related yeast Saccharomyces cerevisiae, the only other
      organism in which meiotic DNA breaks have been reported. Other features, however,
      appear to be different. These results suggest that, although DNA breaks may be a
      general feature of meiotic recombination, the breaks in S. pombe may play a role
      different from those in S. cerevisiae.

PMID- 10882125
TI  - Structure of BamHI bound to nonspecific DNA: a model for DNA sliding.
AB  - The central problem faced by DNA binding proteins is how to select the correct
      DNA sequence from the sea of nonspecific sequences in a cell. The problem is
      particularly acute for bacterial restriction enzymes because cleavage at an
      incorrect DNA site could be lethal. To understand the basis of this selectivity,
      we report here the crystal structure of endonuclease BamHI bound to noncognate
      DNA. We show that, despite only a single base pair change in the recognition
      sequence, the enzyme adopts an open configuration that is on the pathway between
      free and specifically bound forms of the enzyme. Surprisingly, the DNA drops out
      of the binding cleft with a total loss of base-specific and backbone contacts.
      Taken together, the structure provides a remarkable snapshot of an enzyme poised
      for linear diffusion (rather than cleavage) along the DNA.

PMID- 10882126
TI  - Perk is essential for translational regulation and cell survival during the
      unfolded protein response.
AB  - Malfolded proteins in the endoplasmic reticulum (ER) inhibit translation
      initiation. This response is believed to be mediated by increased phosphorylation
      of eukaryotic initiation factor 2alpha (eIF2alpha) and is hypothesized to reduce
      the work load imposed on the folding machinery during stress. Here we report that
      mutating the gene encoding the ER stress-activated eIF2alpha kinase PERK
      abolishes the phosphorylation of eIF2alpha in response to accumulation of
      malfolded proteins in the ER resulting in abnormally elevated protein synthesis
      and higher levels of ER stress. Mutant cells are markedly impaired in their
      ability to survive ER stress and inhibition of protein synthesis by cycloheximide
      treatment during ER stress ameliorates this impairment. PERK thus plays a major
      role in the ability of cells to adapt to ER stress.

PMID- 10882127
TI  - The RFX-type transcription factor DAF-19 regulates sensory neuron cilium
      formation in C. elegans.
AB  - Many types of sensory neurons contain modified cilia where sensory signal
      transduction occurs. We report that the C. elegans gene daf-19 encodes an RFX
      type transcription factor that is expressed specifically in all ciliated sensory
      neurons. Loss of daf-19 function causes the absence of cilia, resulting in severe
      sensory defects. Several genes that function in all ciliated sensory neurons have
      an RFX target site in their promoters and require daf-19 function. Several other
      genes that function in subsets of ciliated sensory neurons do not have an RFX
      target site and are not daf-19 dependent. These results suggest that expression
      of the shared components of sensory cilia is activated by daf-19, whereas cell
      type-specific expression occurs independently of daf-19.

PMID- 10882128
TI  - The ced-8 gene controls the timing of programmed cell deaths in C. elegans.
AB  - Loss-of-function mutations in the gene ced-8 lead to the late appearance of cell
      corpses during embryonic development in C. elegans. ced-8 functions downstream of
      or in parallel to-the regulatory cell death gene ced-9 and may function as a cell
      death effector downstream of the caspase encoded by the programmed cell death
      killer gene ced-3. In ced-8 mutants, embryonic programmed cell death probably
      initiates normally but proceeds slowly. ced-8 encodes a transmembrane protein
      that appears to be localized to the plasma membrane. The CED-8 protein is similar
      to human XK, a putative membrane transport protein implicated in McLeod Syndrome,
      a form of hereditary neuroacanthocytosis.

PMID- 10882129
TI  - A conserved checkpoint pathway mediates DNA damage--induced apoptosis and cell
      cycle arrest in C. elegans.
AB  - To maintain genomic stability following DNA damage, multicellular organisms
      activate checkpoints that induce cell cycle arrest or apoptosis. Here we show
      that genotoxic stress blocks cell proliferation and induces apoptosis of germ
      cells in the nematode C. elegans. Accumulation of recombination intermediates
      similarly leads to the demise of affected cells. Checkpoint-induced apoptosis is
      mediated by the core apoptotic machinery (CED-9/CED-4/CED-3) but is genetically
      distinct from somatic cell death and physiological germ cell death. Mutations in
      three genes--mrt-2, which encodes the C. elegans homolog of the S. pombe rad1
      checkpoint gene, rad-5, and him-7-block both DNA damage-induced apoptosis and
      cell proliferation arrest. Our results implicate rad1 homologs in DNA damage
      induced apoptosis in animals.

PMID- 10882130
TI  - A steroid-triggered transcriptional hierarchy controls salivary gland cell death
      during Drosophila metamorphosis.
AB  - The steroid hormone ecdysone signals the stage-specific programmed cell death of
      the larval salivary glands during Drosophila metamorphosis. This response is
      preceded by an ecdysone-triggered switch in gene expression in which the diap2
      death inhibitor is repressed and the reaper (rpr) and head involution defective
      (hid) death activators are induced. Here we show that rpr is induced directly by
      the ecdysone-receptor complex through an essential response element in the rpr
      promoter. The Broad-Complex (BR-C) is required for both rpr and hid
      transcription, while E74A is required for maximal levels of hid induction. diap2
      induction is dependent on betaFTZ-F1, while E75A and E75B are each sufficient to
      repress diap2. This study identifies transcriptional regulators of programmed
      cell death in Drosophila and provides a direct link between a steroid signal and
      a programmed cell death response.

PMID- 10882131
TI  - Overlapping but distinct RNA elements control repression and activation of nanos
      translation.
AB  - Spatially restricted synthesis of Nanos protein in the Drosophila embryo is
      essential for anterior-posterior patterning. Nanos translation is restricted to
      the posterior of the embryo by translational repression of nanos mRNA throughout
      the bulk cytoplasm and selective activation of posteriorly localized nanos mRNA.
      A 90-nucleotide translational control element (TCE) mediates translational
      repression. We show that TCE function requires formation of a bipartite secondary
      structure that is recognized by Smaug repressor and at least one additional
      factor. We also demonstrate that translational activation requires the
      interaction of localization factors with sequences that overlap TCE structural
      motifs. The identification of separate but overlapping recognition motifs for
      translational repressors and localization factors provides a molecular mechanism
      for the switch between translational repression and activation.

PMID- 10882132
TI  - Rearrangement of a stable RNA secondary structure during VS ribozyme catalysis.
AB  - The Neurospora VS ribozyme recognizes and cleaves a substrate RNA that contains a
      GC-rich stem loop. In contrast to most RNA secondary structures that are stable
      during tertiary or quaternary folding, this substrate undergoes extensive
      ribozyme-induced rearrangement in the presence of magnesium in which the base
      pairings of at least seven of the ten nucleotides in the stem are changed. This
      conformational switch is essential for catalytic activity with the wild-type
      substrate and creates a metal-binding secondary structure motif near the cleavage
      site. Base pair rearrangement is accompanied by bulging a cytosine from the
      middle of the stem, indicating that ribozymes may perform base flipping, an
      activity previously observed only with protein enzymes that modify DNA.

PMID- 10882134
TI  - The yeast hnRNP-like protein Hrp1/Nab4 marks a transcript for nonsense-mediated
      mRNA decay.
AB  - The nonsense-mediated mRNA decay (NMD) pathway monitors premature translation
      termination and degrades aberrant mRNAs. In yeast, it has been proposed that a
      surveillance complex searches 3' of a nonsense codon for a downstream sequence
      element (DSE) associated with RNA-binding proteins. An interaction between the
      complex and the DSE-binding protein(s) triggers NMD. Here we describe the
      identification and characterization of the Hrp1/Nab4 protein as a DSE-binding
      factor that activates NMD. Mutations in HRP1 stabilize nonsense-containing
      transcripts without affecting the decay of wild-type mRNAs. Hrp1p binds
      specifically to a DSE-containing RNA and interacts with Upf1p, a component of the
      surveillance complex. A mutation in HRP1 that stabilizes nonsense-containing
      mRNAs abolishes its affinity for the DSE and fails to interact with Upf1p. We
      present a model describing how Hrp1p marks a transcript for rapid decay.

PMID- 10882133
TI  - Interaction between a poly(A)-specific ribonuclease and the 5' cap influences
      mRNA deadenylation rates in vitro.
AB  - We have used an in vitro system that reproduces in vivo aspects of mRNA turnover
      to elucidate mechanisms of deadenylation. DAN, the major enzyme responsible for
      poly(A) tail shortening in vitro, specifically interacts with the 5' cap
      structure of RNA substrates, and this interaction is greatly stimulated by a
      poly(A) tail. Several observations suggest that cap-DAN interactions are
      functionally important for the networking between regulated mRNA stability and
      translation. First, uncapped RNA substrates are inefficiently deadenylated.
      Second, a stem-loop structure in the 5' UTR dramatically reduces deadenylation by
      interfering with cap-DAN interactions. Third, the addition of cap binding protein
      eIF4E inhibits deadenylation in vitro. These data provide insights into the early
      steps of substrate recognition that target an mRNA for degradation.

PMID- 10882135
TI  - Exit from mitosis in budding yeast: biphasic inactivation of the Cdc28-Clb2
      mitotic kinase and the role of Cdc20.
AB  - Cdc20, an activator of the anaphase-promoting complex (APC), is also required for
      the exit from mitosis in Saccharomyces cerevisiae. Here we show that during
      mitosis, both the inactivation of Cdc28-Clb2 kinase and the degradation of
      mitotic cyclin Clb2 occur in two steps. The first phase of Clb2 proteolysis,
      which commences at the metaphase-to-anaphase transition when Clb2 abundance is
      high, is dependent on Cdc20. The second wave of Clb2 destruction in telophase
      requires activation of the Cdc20 homolog, Hct1/Cdh1. The first phase of Clb2
      destruction, which lowers the Cdc28-Clb2 kinase activity, is a prerequisite for
      the second. Thus, Clb2 proteolysis is not solely mediated by Hct1 as generally
      believed; instead, it requires a sequential action of both Cdc20 and Hct1.

PMID- 10882136
TI  - IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex.
AB  - Here we report the identification of a novel PMA-inducible IkappaB kinase
      complex, distinct from the well-characterized high-molecular weight IkappaB
      kinase complex containing IKKalpha, IKKbeta, and IKKgamma. We have characterized
      one kinase from this complex, which we designate IKKepsilon. Although recombinant
      IKKepsilon directly phosphorylates only serine 36 of IKBalpha, the PMA-activated
      endogenous IKKepsilon complex phosphorylates both critical serine residues.
      Remarkably, this activity is due to the presence of a distinct kinase in this
      complex. A dominant-negative mutant of IKKepsilon blocks induction of NF-kappaB
      by both PMA and activation of the T cell receptor but has no effect on the
      activation of NF-KB by TNFalpha or IL-1. These observations indicate that the
      activation of NF-kappaB requires multiple distinct IkappaB kinase complexes,
      which respond to both overlapping and discrete signaling pathways.

PMID- 10882137
TI  - Control of beta-catenin stability: reconstitution of the cytoplasmic steps of the
      wnt pathway in Xenopus egg extracts.
AB  - Regulation of beta-catenin degradation by intracellular components of the wnt
      pathway was reconstituted in cytoplasmic extracts of Xenopus eggs and embryos.
      The ubiquitin-dependent beta-catenin degradation in extracts displays a
      biochemical requirement for axin, GSK3, and APC. Axin dramatically accelerates
      while dishevelled inhibits beta-catenin turnover. Through another domain,
      dishevelled recruits GBP/Frat1 to the APC-axin-GSK3 complex. Our results confirm
      and extend models in which inhibition of GSK3 has two synergistic effects: (1)
      reduction of APC phosphorylation and loss of affinity for beta-catenin and (2)
      reduction of beta-catenin phosphorylation and consequent loss of its affinity for
      the SCF ubiquitin ligase complex. Dishevelled thus stabilizes beta-catenin, which
      can dissociate from the APC/axin complex and participate in transcriptional
      activation.

PMID- 10882138
TI  - Structure of the dimerization and beta-catenin-binding region of alpha-catenin.
AB  - In adherens junctions, alpha-catenin links the cadherin-beta-catenin complex to
      the actin-based cytoskeleton. alpha-catenin is a homodimer in solution, but forms
      a 1:1 heterodimer with beta-catenin. The crystal structure of the alpha-catenin
      dimerization domain, residues 82-279, shows that alpha-catenin dimerizes through
      formation of a four-helix bundle in which two antiparallel helices are
      contributed by each protomer. A slightly larger fragment, comprising residues 57
      264, binds to beta-catenin. A chimera consisting of the alpha-catenin-binding
      region of beta-catenin linked to the amino terminus of alpha-catenin 57-264
      behaves as a monomer in solution, as expected, since beta-catenin binding
      disrupts the alpha-catenin dimer. The crystal structure of this chimera reveals
      the interaction between alpha- and beta-catenin, and provides a basis for
      understanding adherens junction assembly.

PMID- 10882139
TI  - Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis
      of heterodimerization among nuclear receptors.
AB  - The nuclear receptor PPARgamma/RXRalpha heterodimer regulates glucose and lipid
      homeostasis and is the target for the antidiabetic drugs GI262570 and the
      thiazolidinediones (TZDs). We report the crystal structures of the PPARgamma and
      RXRalpha LBDs complexed to the RXR ligand 9-cis-retinoic acid (9cRA), the
      PPARgamma agonist rosiglitazone or GI262570, and coactivator peptides. The
      PPARgamma/RXRalpha heterodimer is asymmetric, with each LBD deviated
      approximately 10 degrees from the C2 symmetry, allowing the PPARgamma AF-2 helix
      to interact with helices 7 and 10 of RXRalpha. The heterodimer interface is
      composed of conserved motifs in PPARgamma and RXRalpha that form a coiled coil
      along helix 10 with additional charge interactions from helices 7 and 9. The
      structures provide a molecular understanding of the ability of RXR to
      heterodimerize with many nuclear receptors and of the permissive activation of
      the PPARgamma/RXRbeta heterodimer by 9cRA.

PMID- 10882140
TI  - Structure of small virus-like particles assembled from the L1 protein of human
      papillomavirus 16.
AB  - The papillomavirus major late protein, L1, forms the pentameric assembly unit of
      the viral shell. Recombinant HPV16 L1 pentamers assemble in vitro into capsid
      like structures, and truncation of ten N-terminal residues leads to a homogeneous
      preparation of 12-pentamer, icosahedral particles. X-ray crystallographic
      analysis of these particles at 3.5 A resolution shows that L1 closely resembles
      VP1 from polyomaviruses. Surface loops contain the sites of sequence variation
      among HPV types and the locations of dominant neutralizing epitopes. The ease
      with which small virus-like particles may be obtained from L1 expressed in E.
      coli makes them attractive candidate components of a papillomavirus vaccine.
      Their crystal structure also provides a starting point for future vaccine design.

PMID- 10882141
TI  - Molecular and genetic analyses of the silky1 gene reveal conservation in floral
      organ specification between eudicots and monocots.
AB  - The degree to which the eudicot-based ABC model of flower organ identity applies
      to the other major subclass of angrosperms, the monocots, has yet to be fully
      explored. We cloned silky1 (si1), a male sterile mutant of Zea mays that has
      homeotic conversions of stamens into carpels and lodicules into palea/lemma-like
      structures. Our studies indicate that si1 is a monocot B function MADS box gene.
      Moreover, the si1 zag1 double mutant produces a striking spikelet phenotype where
      normal glumes enclose reiterated palea/lemma-like organs. These studies indicate
      that B function gene activity is conserved among monocots as well as eudicots. In
      addition, they provide compelling developmental evidence for recognizing
      lodicules as modified petals and, possibly, palea and lemma as modified sepals.

PMID- 10882142
TI  - The JAK/STAT signaling pathway is required for the initial choice of sexual
      identity in Drosophila melanogaster.
AB  - The choice of sexual identity in Drosophila is determined by a system that
      measures the X chromosome to autosome ratio (X/A). This system depends upon
      unequal expression of X-linked numerator genes in 1X and 2X nuclei. The
      numerators activate a special Sxl promoter, Sxl-Pe, in 2X/2A nuclei, but not
      1X/2A nuclei. By multimerizing a conserved Sxl-Pe sequence block, we generated a
      gain-of-function promoter, Sxl-PeGOF, that is inappropriately active in 1X/2A
      nuclei. GOF activity requires the X-linked unpaired (upd) gene, which encodes a
      ligand for the Drosophila JAK/STAT signaling pathway. upd also functions as a
      numerator element in regulating wild-type Sxl-Pe reporters. We demonstrate that
      the JAK kinase, Hopscotch, and the STAT DNA-binding protein, Marelle, are also
      required for Sxl-Pe activation.

PMID- 10882143
TI  - HATs off: selective synthetic inhibitors of the histone acetyltransferases p300
      and PCAF.
AB  - Histone acetyltransferases (HATs) play important roles in the regulation of gene
      expression. In this report, we describe the design, synthesis, and application of
      peptide CoA conjugates as selective HAT inhibitors for the transcriptional
      coactivators p300 and PCAF. Two inhibitors (Lys-CoA for p300 and H3-CoA-20 for
      PCAF) were found to be potent (IC(50) approximately = 0.5 microM) and selective
      (approximately 200-fold) in blocking p300 and PCAF HAT activities. These
      inhibitors were used to probe enzymatic and transcriptional features of HAT
      function in several assay systems. These compounds should be broadly useful as
      biological tools for evaluating the roles of HATs in transcriptional studies and
      may serve as lead agents for the development of novel antineoplastic
      therapeutics.

PMID- 10882144
TI  - Absence of response to human parathyroid hormone in athymic mice grafted with
      human parathyroid adenoma, hyperplasia or parathyroid cells maintained in
      culture.
AB  - In athymic mice we have developed a model of long-term human PTH hypersecretion,
      using xenotransplantation of respectively parathyroid gland fragments obtained
      from patients with primary (primary) or secondary (secondary) uremic
      hyperparathyroidism (HPT), and parathyroid cells maintained in culture from
      patients with secondary uremic HPT. Both grafted parathyroid tissue fragments and
      cultured cells induced prolonged and marked secretion of human intact PTH (iPTH)
      in nude mice. Despite extremely high plasma iPTH levels, hypercalcemia or
      hypophosphatemia was not observed. Moreover, PTH secretion was not significantly
      modified by low-calcium, high-phosphate diet for 3 weeks. Four mice which had a
      mean plasma human iPTH level of 237+/-152 pg/ml for more than 9 months and 4 age
      matched, sham-grafted control mice with undetectable human iPTH levels underwent
      bone histomorphometry examination. No difference was found between the two groups
      with respect to active bone resorption surface or number of osteoclasts/mm2. We
      hypothesize that the characteristic deficit of T cell function and of cytokine
      and growth factor production may protect nude mice with chronic hypersecretion of
      human PTH from hypercalcemia and bone lesions. We suggest that this strain of
      mice could be used for better understanding the relationship between cytokines
      and bone turnover.

PMID- 10882145
TI  - Metabolic effects of fluoxetine in obese menopausal women.
AB  - Our objective was to assess thermogenic action of fluoxetine (FL) in obese
      menopausal women, evaluating the effect of FL administration on resting energy
      expenditure (REE) and on glucose-induced thermogenesis both after acute
      administration (40 mg in single dose the evening before measurements) and after a
      12- week period of diet treatment plus FL (60 mg per day) or placebo. It was a
      double-blind, placebo-controlled design both in acute and in chronic study. The
      subjects were 32 obese, otherwise healthy, menopausal women. The patients were
      assigned randomly to three groups, one performing an acute study protocol, in
      which resting and glucose-induced thermogenesis was measured after FL and placebo
      administration, performed in randomised order. The other two groups underwent
      dietary plus pharmacological treatment (FL or placebo, PL). Resting and glucose
      induced thermogenesis was measured at baseline and after 12 weeks of treatment.
      The results showed that acute FL administration caused an increase in resting
      energy expenditure (PL: 5.35+/-0.18 vs FL: 5.53+/-0.24 KJ/min, p<0.05). A
      significant decrease of REE was observed in the PL group after 12 weeks (p<0.03),
      while a slight, but not significant, decrease was observed in the FL group
      (p=NS). FL did not affect thermic response to oral glucose neither after acute
      nor chronic administration (p=NS for all groups studied). The conclusion was that
      our data give support to thermogenic actions of FL after acute administration,
      suggesting also that chronic FL treatment may restrain to some degree the
      metabolic adaptation expected during weight loss in obese subjects. At variance
      with what observed with other drugs, such as dexfenfluramine, an increased
      thermic effect of oral glucose does not seem to be involved in the thermogenetic
      action of FL.

PMID- 10882146
TI  - Comparative analysis of plasma 17-hydroxyprogesterone and cortisol responses to
      ACTH in patients with various adrenal tumors before and after unilateral
      adrenalectomy.
AB  - Patients with non-hyperfunctioning adrenal adenomas often have an increased
      plasma 17-hydroxyprogesterone response to ACTH stimulation. The effects of
      adrenal surgery on this abnormality have rarely been investigated. One hundred
      and sixty-one patients with unilateral adrenal tumors (non-hyperfunctioning
      adenomas, 78; cortisol-producing adenomas, 8; aldosterone-producing adenomas, 37;
      adrenal cysts, 12; pheochromocytomas, 26) were studied. Patients before and after
      adrenal surgery as well as 60 healthy subjects underwent an ACTH stimulation test
      using 2 mg synthetic ACTH(1-24) (Cortrosyn Depot, Organon). Basal and ACTH
      stimulated plasma 17-hydroxyprogesterone and cortisol concentrations are
      reported. Before adrenal surgery, the basal plasma 17-hydroxyprogesterone
      concentrations were normal in patients with all types of tumors. However, the
      ACTH-stimulated plasma 17-hydroxyprogesterone levels were abnormally increased in
      53% and 31% of patients with non-hyperfunctioning adenomas and aldosterone
      producing adenomas, respectively. In addition, a few patients with adrenal cysts
      and pheochromocytomas also showed an increased ACTH-stimulated 17
      hydroxyprogesterone response. After unilateral adrenalectomy, this hormonal
      abnormality disappeared in most, although not all patients with adrenal tumors.
      In patients with non-hyperfunctioning adrenal tumors, ACTH-stimulated plasma 17
      hydroxyprogesterone and cortisol concentrations significantly correlated with the
      size of the tumors. These results firmly indicate that the tumoral mass itself
      may be responsible for the increased plasma 17-hydroxyprogesterone and cortisol
      responses after ACTH stimulation in patients with non-hyperfunctioning and
      hyperfunctioning adrenal adenomas.

PMID- 10882147
TI  - Osteopenia in insulin-dependent diabetes mellitus; prevalence and aspects of
      pathophysiology.
AB  - The objective was to evaluate the prevalence and severity of osteopenia in
      patients with uncomplicated insulin-dependent diabetes mellitus (IDDM) and to
      obtain more information on the pathophysiology of diabetic osteopenia. In 35
      patients with uncomplicated IDDM (21 men and 14 women; age 37.6+/-9.9 yr;
      duration of disease 8.5+/-3.5 years) bone mineral density was measured by dual
      energy X-ray absorptiometry (DEXA). In addition, markers of bone formation
      [plasma insulin-like growth factor I (IGF-I), serum alkaline phosphatase (ALP),
      serum bone alkaline phosphatase (BAP) and serum osteocalcin] and bone resorption
      [urinary excretion of calcium and of the cross-linked N-telopeptide of type 1
      collagen, both corrected for the excretion of creatinine] were measured in the
      diabetic patients and in 33 healthy controls, matched for sex, age, height,
      weight and body mass index (BMI). In 67% of the diabetic men and 57% of the
      diabetic women osteopenia of the femoral neck and/or the lumbar spine (T-value <
      or = -1 SD) was present. Fourteen percent of the male patients, but none of the
      female patients, met the criteria for osteoporosis (T-value < or = -2.5 SD). In
      the whole group of diabetic patients the mean plasma IGF-I level tended to be
      lower (p<0.10) as compared to that in the controls. In the diabetic patients with
      femoral neck osteopenia, the mean plasma IGF-I level was significantly lower
      (p<0.05) than in those without osteopenia at this site. There were no differences
      in the mean serum ALP, BAP and osteocalcin levels between the diabetic patients
      and the controls, nor between the diabetic patients with and without femoral neck
      osteopenia. Considering only the male diabetic patients, significantly lower mean
      plasma IGF-I (-26%), serum ALP (-24%) and serum osteocalcin (-38%) levels were
      present in the patients with femoral neck osteopenia than in those without
      osteopenia at this site, suggesting lowered bone formation. The bone resorption
      markers were similar in all (sub)groups of diabetic patients and not different
      between diabetic patients and controls. Bone mineral density (BMD) did not
      correlate with plasma levels of glycosylated hemoglobin (HbA1c). BMD values were
      not related to any of the bone resorption or formation markers, except for plasma
      IGF-I both in the femoral neck (r=+0.38, p=0.026) and the lumbar spine (r=+0.34,
      p=0.043). Our data demonstrate that at least in male patients with IDDM,
      osteopenia is the consequence of a lowered bone formation with a predominance of
      bone resorption over formation.

PMID- 10882148
TI  - Screening for MEN1 tumor suppressor gene mutations in sporadic pituitary tumors.
AB  - The molecular pathogenesis of the majority of sporadic pituitary tumors is
      largely unknown. Pituitary adenomas can develop sporadically or as a part of
      multiple endocrine neoplasia type 1 (MEN1). The MEN1 is thought to be a tumor
      suppressor gene based on loss of heterozygosity (LOH) for polymorphic markers on
      11q13 in tumors of the pancreas, parathyroid, and pituitary. Most patients with
      familial and sporadic MEN1 carry germ-line mutations in the MEN1 gene. Two
      previous studies and recently a third one have analyzed mutations by sequencing
      the MEN1 gene in sporadic pituitary tumors but yielded conflicting results. This
      study was to investigate and clarify the potential role of MEN1 mutations, in
      sporadic pituitary adenomas. First, we examined 59 sporadic pituitary adenomas by
      analyzing LOH on 11q13 in the MEN1 minimal interval with microsatellite analysis.
      We found 3 tumors with LOH in 1 to 4 polymorphic markers in the MEN1 region.
      Sequencing analysis did not reveal any mutations in the coding region of the MEN1
      gene. However, we found 3 polymorphisms, one of which was a novel CAC to CAT
      transition encoding His433His, in exon 9. The data show that while LOH occurs in
      some sporadic pituitary tumors, inactivating mutations of the tumor suppressor
      gene MEN1 are rare. These results also suggest there may be another additional
      tumor suppressor gene at this locus which is involved in the pathogenesis of
      sporadic pituitary neoplasms.

PMID- 10882149
TI  - Prevention of early postmenopausal bone loss with cyclical etidronate.
AB  - Cyclical etidronate has been shown to be effective in the treatment of
      established postmenopausal osteoporosis but less is known about its effects on
      early menopausal bone loss. The aim of the study was to establish the effects of
      cyclic etidronate therapy on spinal and proximal femoral bone mineral loss in
      early postmenopausal women. One hundred and seven women who were within 6 months
      to 3 years of the menopause were recruited into a 2-year, randomised, placebo
      controlled, double-blind trial. Spinal bone mineral density was within 2 SD of
      the age-matched mean reference value at baseline. Bone mineral density in the
      lumbar spine and proximal femur was assessed by dual energy X-ray absorptiometry
      at baseline and thereafter at 6 monthly intervals for 2 years. Urinary collagen
      cross-links (deoxypyridinoline and pyridinoline) were measured at the same time
      points. Seventy-seven women completed the study. At the end of the treatment
      period, the mean bone mineral density change from baseline in the treated group
      was +0.14% and -0.06% in the lumbar spine and femoral neck, respectively,
      compared to -1.49 and -2.22 in the control group. Overall, there was a
      significant difference between the two groups at both these sites (p=0.01 and
      0.001, respectively). No significant differences between the groups were
      demonstrated at the greater trochanter or Ward's triangle. The conclusion was
      that cyclical etidronate therapy prevents bone loss in the spine and femoral neck
      in early postmenopausal women. It provides a safe and effective therapeutic
      option for the prevention of postmenopausal osteoporosis in women who are
      unwilling or unable to tolerate hormone replacement therapy.

PMID- 10882150
TI  - Female pseudohermaphroditism and inefficient peak bone mass in an untreated
      subject affected by 21-hydroxylase congenital adrenal hyperplasia.
AB  - Here we describe a subject with congenital adrenal hyperplasia due to 21
      hydroxylase deficiency (21-CAH), in its classical virilizing form, who presented
      at birth ambiguous genitalia and subsequently was assigned by the parents as
      male. At the age of 8 years, he underwent a two-step surgical correction of
      hypospadia and at 22 years old, uterus and ovaries were removed and a bilateral
      testicular prothesis was surgically placed in scrotum. He refused any chronic
      glucocorticoid therapy, that was given only acutely to prevent adrenal crises
      during stress, trauma surgery or severe illness. The patient is now 38 years old,
      he is genotypically female but phenotypically male, with high endogenous levels
      of androgen, all of adrenal origin, and with an apparent male sexual life. He had
      severe osteopenia, probably due to the lack of estrogen/androgen-induced increase
      in bone mineral density, although periferal estrogen conversion was normal. His
      skeletal mass, in fact, normally acquired during adolescence and early adult
      life, could in this case be inefficient, for the precocious pseudopuberty, that
      caused an inefficient peak bone mass in adolescence period.

PMID- 10882151
TI  - Long-term treatment with interferon-beta therapy for multiple sclerosis and
      occurrence of Graves' disease.
AB  - Interferon (IFN)-beta has become a widespread therapy for multiple sclerosis. As
      already reported for IFN-alpha, thyroid autoimmunity and dysfunctions have been
      observed also in course of IFN-beta therapy. Nevertheless, very few cases of
      Graves' disease, occurred in such condition, have been reported in literature. We
      here describe the case of a 40-year-old female affected by multiple sclerosis,
      who received IFN-beta-1b, 8 million IU s.c. every other day for her condition.
      After 22 months of cytokine administration, she developed a severe Graves'
      disease with persistently positive TR-Ab which suggested the withdrawal of the
      treatment. Our patient had performed a complete thyroid evaluation with normal
      findings, before and during the first 6 months of therapy. This case suggests
      that patients undergoing long-term IFN-beta therapy should be monitored for
      thyroid hormones and antibodies throughout the treatment as thyroidal side effect
      can be a late event.

PMID- 10882152
TI  - Inferior petrosal sinus sampling ten years down the road.

PMID- 10882154
TI  - Lymphocytic hypophysitis and autoimmune thyroid disease.

PMID- 10882153
TI  - RET proto-oncogene mutations in thyroid carcinomas: clinical relevance.
AB  - Different forms of RET mutations are found in papillary and medullary thyroid
      carcinomas. Rearrangements with other genes (RET/PTC oncogene) play a causative
      role in a significant proportion of papillary thyroid carcinomas. In this case,
      several factors influence the frequency and the type of RET/PTC, such as exposure
      to radiation, age and histological variant of the papillary tumor. On the other
      hand, the presence of the mutation does not seem to influence the biological
      behavior of the tumor or its response to conventional treatment modalities. In
      the setting of medullary thyroid cancer, germline RET point-mutations are
      implicated in the pathogenesis of virtually all hereditary forms and somatic
      point-mutations in nearly half of the sporadic forms. The clinical impact of this
      finding is that family members at-risk of hereditary MTC may be screened by
      genetic analysis, to distinguish those carrying or not-carrying the mutation. The
      last can be reassured on their status and relieved from further follow-up. Those
      with the mutation may be treated at a pre-clinical stage of the disease or even
      before the disease is started. The present review is focused on the clinical
      implication of RET gene mutations in thyroid cancer patients.

PMID- 10882155
TI  - Diagnosis and medical-surgical treatment of cryptorchidism.

PMID- 10882156
TI  - "The dancer dwarf". Pablo Picasso. Malaga, Spain (1881)-Mougins, France (1973).

PMID- 10882157
TI  - COX-2 selective nonsteroidal anti-Inflammatory drugs: do they really offer any
      advantages?
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for substantial
      morbidity and mortality as a result of the complications associated with
      gastroduodenal ulcers, such as perforation and bleeding. The central mechanism
      leading to the gastroduodenal toxicity of NSAIDs is their ability to inhibit
      mucosal prostaglandin synthesis. Recent recognition that there are 2 isoforms of
      the enzyme cyclooxygenase (COX) responsible for prostaglandin synthesis has
      enabled the development of drugs capable of sparing the gastric mucosa. The
      inducible COX-2 enzyme is responsible for some aspects of pain and inflammation
      in arthritis while the constitutive COX-1 enzyme appears responsible for most of
      the gastro-protective prostaglandin synthesis in the stomach and duodenum. Drugs
      selective for COX-2 probably act by binding to a pocket in the enzyme that is
      present in COX-2 but not in COX-1. As a result, drugs that have little or no COX
      1 activity across their therapeutic dosage range have been developed. Two drugs
      that are claimed to be highly selective or specific in their ability to inhibit
      COX-2, rofecoxib and celecoxib, are now available on prescription in the US and
      rofecoxib is available in Europe. Short term volunteer studies of 7 days'
      duration and patient studies of 6 months' duration have shown these drugs to have
      a level of gastroduodenal injury that is similar or equivalent to that seen with
      placebo, whereas high rates of damage and ulceration are seen with nonselective
      NSAIDs. In addition, there appear to have been fewer perforations, clinical
      ulcers and bleeds in the phase III clinical trials of these agents, compared with
      nonselective NSAIDS. However, more experience will be needed before this promise
      can be confirmed. In addition, COX-2 inhibitors share the adverse effects of
      NSAIDs outside the gastrointestinal tract that are dependent on COX-2 inhibition.

PMID- 10882158
TI  - Development of an asthma vaccine: research into BCG.
AB  - Asthma is an atopic disorder characterised by the activation and recruitment of
      eosinophils to the lung resulting in chronic swelling and inflammation of the
      airways. Allergic disorders such as atopic asthma and dermatitis have been
      increasingly prevalent in developed countries, and the inverse correlation
      between exposure to major diseases such as tuberculosis and atopy prevalence has
      been reported. Intranasal administration of Mycobacterium bovis-Bacillus Calmette
      Guerin (BCG) has been demonstrated to suppress airway eosinophilia in a model of
      atopic asthma. This immunomodulation is attributed to the ability of interferon
      (IFN)-gamma produced by BCG-specific T(H)1 lymphocytes to inhibit the development
      of lung T(H)2 responses such as airway eosinophilia. The mechanism of IFNgamma
      induced inhibition is yet to be defined, but could involve activation of
      macrophages, direct suppression of developing T(H)2 lymphocytes, or altered
      dendritic cell activation and antigen presentation. Mycobacteria such as BCG and
      certain mycobacterial fractions are strong inducers of a T(H)1 immune response.
      The effectiveness of BCG in inhibiting atopic airway eosinophilia suggests its
      potential as a useful therapeutic agent in the treatment of atopic asthma.

PMID- 10882159
TI  - Carrier systems for the local delivery of antibiotics in bone infections.
AB  - Carriers used for the local delivery of antibacterial agents may be classified as
      nonbiodegradable or biodegradable. A major representative of the former category
      are the polymethylmethacrylate (PMMA) beads often impregnated with gentamicin
      which have been commercially available for the last 2 decades. Examples of the
      latter category include the collagen-gentamicin sponge, apatite-wollastonite
      glass ceramic blocks, hydroxyapatite blocks, polylactide/polyglycolide implants
      and the polylactate polymers. All of the above systems release antibiotics at
      concentrations exceeding those of the minimum inhibitory concentrations (MICs)
      for the most common pathogens of chronic osteomyelitis without releasing any
      antibiotic in the systemic circulation and without producing adverse effects. The
      major disadvantage of the PMMA beads is the need for their surgical removal at
      the completion of antibiotic release, which usually takes place 4 weeks after
      their implantation. The biodegradable carriers do not require surgical removal,
      and of those listed, the collagen-gentamicin sponge has been applied successfully
      over the last decade for bone infections. Among the other biodegradable systems
      which are still in experimental stages, polylactate polymers carrying quinolones
      seem very promising, since they are characterised by prolonged duration of
      release at concentrations 100 to 1000 times the MICs of the causative bacteria
      implicated in bone infections; preliminary results have shown these carriers to
      be very effective in the management of experimental osteomyelitis caused by
      methicillin-resistant Staphylococcus aureus. Further development of such
      biodegradable systems will provide a novel approach in the future for the
      eradication of chronic osteomyelitis.

PMID- 10882160
TI  - Clinical pharmacology, therapeutic use and potential of COMT inhibitors in
      Parkinson's disease.
AB  - When peripheral decarboxylation is blocked by carbidopa or benserazide, the main
      metabolic pathway of levodopa is O-methylation by catechol-O-methyltransferase
      (COMT). Entacapone and tolcapone are new potent, selective and reversible
      nitrocatechol-type COMT inhibitors. Animal studies have demonstrated that
      entacapone mainly has a peripheral effect whereas tolcapone also inhibits O
      methylation in the brain. In human volunteers, both entacapone and tolcapone dose
      dependently inhibit the COMT activity in erythrocytes, improve the
      bioavailability and decrease the elimination of levodopa, and inhibit the
      formation of 3-O-methyldopa (3-OMD). Entacapone is administered with every
      scheduled dose of levodopa whereas tolcapone is administered 3 times daily. The
      different administration regimens for these agents are based on their different
      pharmacokinetic and pharmacodynamic profiles. Both entacapone and tolcapone
      enhance and extend the therapeutic effect of levodopa in patients with advanced
      and fluctuating Parkinson's disease. They prolong the duration of levodopa
      effect. Clinical studies show that they increase the daily ON time by an average
      1 to 3 hours, improve the activities of daily living and allow daily levodopa
      dosage to be decreased. Correspondingly, they significantly reduce the daily OFF
      time. No comparative studies between entacapone and tolcapone have been
      performed. Tolcapone also appears to have a beneficial effect in patients with
      nonfluctuating Parkinson's disease. The main adverse effects of the COMT
      inhibitors are related to their dopaminergic and gastrointestinal effects.
      Enhancement of dopaminergic activity may cause an initial worsening of levodopa
      induced adverse effects, such as dyskinesia, nausea, vomiting, orthostatic
      hypotension, sleep disorders and hallucinations. Levodopa dose adjustment is
      recommended to avoid these events. Tolcapone is associated with diarrhoea in
      about 16 to 18% of patients and entacapone in less than 10% of patients.
      Diarrhoea has led to discontinuation in 5 to 6% of patients treated with
      tolcapone and in 2.5% of those treated with entacapone. Urine discoloration to
      dark yellow or orange is related to the colour of COMT inhibitors and their
      metabolites. Elevated liver transaminase levels are reported in 1 to 3% of
      patients treated with tolcapone but very rarely, if at all, in patients treated
      with entacapone. The descriptions of acute, fatal fulminant hepatitis and
      potentially fatal neurological reactions, such as neuroleptic malignant syndrome
      and rhabdomyolysis, in association with tolcapone led to the suspension of its
      marketing authorisation in the European Community and Canada. In many other
      countries, the use of tolcapone is restricted to patients who are not responding
      satisfactorily to other therapies. Regular monitoring of liver enzymes is
      required if tolcapone is used. No such adverse reactions have so far been
      described for entacapone and no laboratory monitoring has been proposed. COMT
      inhibitors added to levodopa therapy are beneficial, particularly in patients
      with fluctuating disease. They may be combined with other antiparkinsonian drugs,
      such as dopamine agonists, selegiline and anticholinergics without adverse
      interactions. They provide a new treatment possibility in patients with
      Parkinson's disease who have problems with their present levodopa therapy.

PMID- 10882161
TI  - HIV-associated peripheral neuropathy: epidemiology, pathophysiology and
      treatment.
AB  - Peripheral neuropathy is the most frequent neurological complication associated
      with human immunodeficiency virus type 1 (HIV) infection and advanced acquired
      immunodeficiency syndrome (AIDS). There are at least 6 patterns of HIV-associated
      peripheral neuropathy, although these diagnoses are often overlooked or
      misdiagnosed. Distal symmetrical polyneuropathy (DSP) is the most common form of
      peripheral neuropathy in HIV infection. DSP occurs mainly in patients with
      advanced immunosuppression and may also be secondary to the neurotoxicity of
      several antiretroviral agents. Treatment of painful DSP is primarily symptomatic,
      while pathogenesis-based therapies are under investigation. Reduction or
      discontinuation of neurotoxic agents should be considered if possible.
      Inflammatory demyelinating polyneuropathy (IDP) can present in an acute or
      chronic form. The acute form may occur at the time of primary HIV infection or
      seroconversion. Cerebrospinal fluid lymphocytic pleocytosis (10 to 50 cells/mm3)
      is helpful in the diagnosis of HIV-associated IDP. Treatment consists of
      immunomodulatory therapy. Progressive polyradiculopathy (PP) most commonly occurs
      in advanced immunosuppression and usually is caused by cytomegalovirus (CMV)
      infection. Rapidly progressive flaccid paraparesis, radiating pain and
      paresthesias, areflexia and sphincter dysfunction are the cardinal clinical
      features. Rapid diagnosis and treatment with anti-CMV therapy are necessary to
      prevent irreversible neurological deficits resulting from nerve root necrosis.
      Mononeuropathy multiplex (MM) that occurs in early HIV infection is characterised
      by self-limited sensory and motor deficits in the distribution of individual
      peripheral nerves. In advanced HIV infection, multiple nerves in two or more
      extremities or cranial nerves are affected. Treatment includes immunomodulation
      or anti-CMV therapy. Autonomic neuropathy may be caused by central or peripheral
      nervous system abnormalities. Treatment is supportive with correction of
      metabolic or toxic causes. Diffuse infiltrative lymphocytosis syndrome (DILS)
      presents as a Sjogren's-like disorder with CD8 T cell infiltration of multiple
      organs. Antiretroviral therapy and steroids may be effective treatments.

PMID- 10882162
TI  - Neuroblastoma: current drug therapy recommendations as part of the total
      treatment approach.
AB  - Neuroblastoma represents one of the most challenging malignancies for treatment
      decisions because of its unusual biological behaviour. The features include
      spontaneous regression (regressive type), maturation to ganglioneuroma
      (maturative type) and largely treatment-resistant progression (progressive type).
      Current knowledge allows only partial prediction of type. For practical reasons,
      patients may be categorised as an 'observation', a 'standard risk' or a 'high
      risk' treatment arm. During the last 2 decades, 5-year survival rates for
      children with neuroblastoma have increased from 48 to 67%. The main achievements
      were the reduction of chemotherapy in patients with localised disease and the
      increased efficacy of chemotherapy in metastatic neuroblastoma stage 4 (5-year
      survival increased from 8 to 33%). Different goals for chemotherapy (e.g.
      stopping rapid progression, improvement of symptoms, induction and maintenance of
      remission) require different dosages and durations of treatment (range 1 week to
      9 months). The main risks of chemotherapy are toxic death (rate up to 15%)
      predominantly during the periods of bone marrow depression and the development of
      secondary leukaemias (up to 7% cumulative risk after 4 years). In conclusion, the
      use of cytotoxic drugs can be completely omitted in a substantial proportion of
      low risk patients with neuroblastoma. On the other hand, for high risk patients
      with the disease, intensive polychemotherapy represents the basis and the
      backbone of treatment among other modalities.

PMID- 10882163
TI  - Exemestane: a review of its use in postmenopausal women with advanced breast
      cancer.
AB  - Exemestane is an orally active irreversible steroidal aromatase inactivator that
      effectively suppresses in vivo aromatase activity and circulating estrogen levels
      in postmenopausal women with advanced breast cancer. In clinical trials, tumour
      responses were elicited by exemestane regardless of disease site, importantly, in
      patients with visceral disease. In patients with disease refractory to tamoxifen,
      once daily exemestane 25 mg produced objective response rates of 15 to 28% that
      were sustained for a median duration of 69 to 76 weeks. In a large comparative
      study, exemestane and megestrol showed similar clinical efficacy according to
      objective response and overall success rates. However, the duration of overall
      success and times to disease progression and treatment failure were significantly
      prolonged with exemestane compared with megestrol. Additionally, a significant
      survival advantage for exemestane over megestrol was reported. Exemestane retains
      efficacy in patients refractory to multiple hormonal therapies. In patients whose
      disease had progressed after tamoxifen and megestrol, objective response rates of
      11 and 13% were reported, and responses were similar regardless of whether
      megestrol resistance was de novo or acquired. Objective responses also occurred
      in studies that explored sequential use of exemestane after failure of
      aminoglutethimide (26% with exemestane 200 mg/day) or other nonsteroidal
      aromatase inhibitors (6.6% with exemestane 25 mg/day). Additionally, tumour
      responses (objective response 6.1%, overall success rate 24.7%) were reported in
      patients who had not responded to their last hormonal treatment. As first-line
      treatment, once daily exemestane 25 mg elicited objective and overall success
      rates of 42 and 58%, compared with 16 and 31% for once daily tamoxifen 20 mg.
      Exemestane was generally well tolerated in clinical trials at once daily dosages
      up to 600 mg. At the 25 mg recommended once daily dosage, the most commonly
      occurring adverse events were nausea, hot flushes, fatigue, increased sweating
      and dizziness. Weight gain occurred in significantly more patients receiving
      megestrol than among those treated with exemestane. Androgenic events have been
      reported in a small number of patients receiving once daily exemestane 200 mg,
      but were rarely reported at the recommended dosage. CONCLUSIONS: Exemestane is
      effective in postmenopausal patients with tamoxifen-refractory advanced breast
      cancer, prolonging time to disease progression and treatment failure and
      improving survival compared with megestrol treatment. Moreover, exemestane has an
      acceptable tolerability profile and a convenient once daily oral dosage regimen.
      Available data indicate that exemestane maintains its efficacy in patients with
      visceral metastases and does not show cross-resistance with nonsteroidal
      aromatase inhibitors. Preliminary data indicate that exemestane is also effective
      as first-line therapy for advanced breast cancer.

PMID- 10882164
TI  - Tropisetron: an update of its use in the prevention of chemotherapy-induced
      nausea and vomiting.
AB  - Tropisetron is a serotonin (5-hydroxytryptamine; 5-HT) antagonist that is
      primarily used in the prevention of chemotherapy-induced nausea and vomiting.
      Antagonism of 5-HT3 binding sites in the peripheral and central nervous system is
      the probable mechanism of prevention of acute nausea and vomiting. Effects on
      delayed nausea and vomiting are less well understood as these are probably not
      mediated solely by 5-HT3 receptors. Tropisetron monotherapy is effective for the
      control of acute, and to a lesser extent delayed, nausea and vomiting in patients
      receiving moderately to severely emetogenic chemotherapy. The combination of
      dexamethasone and tropisetron is more effective than monotherapy. Complete
      control of cisplatin-induced nausea and vomiting was obtained in 69 to 97% of
      patients receiving the combination compared with 46 to 80% receiving tropisetron
      monotherapy in randomised trials. There were generally no significant differences
      between the control of acute or delayed nausea and vomiting provided by
      tropisetron, ondansetron or granisetron in randomised, comparative trials. The
      antiemetic efficacy of tropisetron was maintained over multiple cycles of
      chemotherapy. Most comparative studies showed tropisetron monotherapy to be more
      effective than metoclopramide in controlling acute nausea and vomiting, with the
      exception of 1 study which showed similar efficacy. However, high dose
      metoclopramide plus dexamethasone provided similar control of delayed emesis to
      tropisetron plus dexamethasone. Tropisetron is also effective in children,
      including those who responded poorly to previous antiemetic treatment.
      Tropisetron and ondansetron generally have similar efficacies in this population.
      The drug enhanced patients' quality of life and was well tolerated by adults and
      children alike. The recommended oral and IV dosage of tropisetron is 5 mg once
      daily; there is no increase in efficacy with doses >5 mg. CONCLUSIONS:
      Tropisetron is similar to other 5-HT3 receptor antagonists for the prevention of
      chemotherapy-induced nausea and vomiting in both adults and children. It is
      suitable as first-line therapy (combined with a corticosteroid) for the
      prevention of acute nausea and vomiting in patients treated with moderately to
      severely emetogenic chemotherapeutic agents. This combination is also moderately
      effective in the prevention of delayed nausea and vomiting.

PMID- 10882167
TI  - On the thermal unfolding character of globular proteins.
AB  - A theoretical model is presented to study the stepwise thermal unfolding of
      globular proteins using the stabilizing/destabilizing characters of amino acid
      residues in protein crystals. A multiple regression relation connecting the
      melting temperature and the amounts of stabilizing and destabilizing groups of
      residues in a protein, when used for the thermal behavior of peptide segments,
      provides reliable results on the stepwise unfolding nature of the protein. In
      ribonuclease A, the shell residues 16-22 are predicted to unfold earlier in the
      temperature range 30-45 degrees C; the beta-sheet structures undergo thermal
      denaturation as a single cooperative unit and there is evidence indicating the
      segment 106-118 as a nucleation site. In ribonuclease S, the S-peptide unfolds
      earlier than S-protein. The predicted average and the range of melting
      temperatures, and the folding pathways of a set of globular proteins, agree very
      well with the experimental results. The results obtained in the present study
      indicate that (i) most of the nucleation parts possess high relative thermal
      stability, (ii) the unfolded state retains some residual structure, and (iii)
      some segments undergo gradual and overlapping thermal denaturation.

PMID- 10882165
TI  - Valaciclovir: a review of its use in the management of herpes zoster.
AB  - Varicella zoster virus (VZV), the pathogen responsible for herpes zoster, belongs
      to the herpesvirus family and is sensitive to the antiviral drug aciclovir.
      However, the low oral bioavailability of aciclovir has to some extent limited its
      efficacy in the treatment of herpes zoster and has prompted the development of
      the more readily absorbed oral prodrug valaciclovir. In a large comparative study
      valaciclovir, (1000 mg 3 times daily for 7 days) was at least as effective as
      aciclovir (800 mg 5 times daily for 7 days) in controlling the symptoms of acute
      herpes zoster. Importantly, valaciclovir alleviated zoster-associated pain and
      postherpetic neuralgia significantly faster than aciclovir. A 14-day regimen of
      valaciclovir showed no significant advantage over the 7-day regimen. A smaller
      trial in Japanese patients focusing primarily on the cutaneous (rash) signs of
      herpes zoster confirmed the similar efficacy of valaciclovir and aciclovir in the
      7-day regimen. This study did not follow all patients for a formal analysis of
      postherpetic neuralgia. Valaciclovir and aciclovir demonstrated similar efficacy
      for the control of cutaneous lesions and ocular complications in patients with
      zoster ophthalmicus. Preliminary results of a large controlled trial indicate
      that valaciclovir 1000 mg 3 times daily and famciclovir (the prodrug of
      penciclovir) 500 mg 3 times daily are of similar efficacy in speeding resolution
      of acute herpes zoster rash and shortening the duration of postherpetic
      neuralgia. Starting treatment later than 72 hours after rash onset did not
      significantly reduce the beneficial effect of valaciclovir on duration of zoster
      associated pain (a continuum of pain that encompasses both acute pain and
      postherpetic neuralgia) in a large observational study, suggesting that
      valaciclovir might be effective when given later than previously thought.
      However, valaciclovir should ideally be given as soon as possible after symptoms
      appear. With the recommended regimen for the treatment of herpes zoster (1000 mg
      3 times daily for 7 days) valaciclovir was well tolerated, with nausea and
      headache being the most commonly reported adverse events. The adverse events
      profile of the agent was similar to that seen with aciclovir or famciclovir.
      CONCLUSION: The efficacy of valaciclovir for the treatment of herpes zoster has
      been confirmed and extended by follow-up studies in herpes zoster ophthalmicus,
      in Japanese patients, and in the wider primary care setting. Valaciclovir is at
      least equivalent to, and better in certain parameters than, aciclovir and appears
      to have similar efficacy to famciclovir 500 mg 3 times daily. Valaciclovir is a
      well tolerated first-line therapy with an established place in the treatment of
      immunocompetent patients with herpes zoster.

PMID- 10882166
TI  - Infliximab: a review of its use in the management of rheumatoid arthritis.
AB  - Infliximab is a chimaeric monoclonal antibody to human tumour necrosis factor
      alpha (TNFalpha). It binds to both soluble and transmembrane forms of TNFalpha at
      picomolar concentrations in vitro. Secondary to inhibition of TNFalpha,
      infliximab reduces serum levels of inflammatory mediators and vascular
      endothelial growth factor, decreases the expression of chemokines in the synovial
      tissue and reduces lymphocyte migration into the joints of patients with
      rheumatoid arthritis. In 2 multicentre randomised double-blind trials conducted
      over 26 and 30 weeks, infliximab plus methotrexate was significantly more
      effective than placebo plus methotrexate according to American College of
      Rheumatology response criteria in patients with active rheumatoid arthritis. A
      substantial response to infliximab-containing regimens was evident within 2
      weeks. Extension phases of these studies indicate sustained clinical efficacy for
      up to 54 weeks. Of considerable importance are preliminary 1-year radiographic
      findings that show zero median progression of joint damage in infliximab plus
      methotrexate recipients compared with a 7 to 8% deterioration in placebo plus
      methotrexate recipients. Headache, nausea, upper respiratory tract infection and
      infusion-related reactions are the most commonly reported adverse events with
      infliximab. Serious events occurred in 4.4% of infliximab versus 1.8% of placebo
      recipients. In the largest clinical trial, 2 patients died from disseminated
      infection and 3 developed new or recurrent malignancies, although the exact
      relationship between infliximab and these events is unknown. To date, 2 patients
      with rheumatoid arthritis have developed drug-induced lupus. About 10% of
      patients may develop antibodies to infliximab, although the clinical significance
      of these is presently unknown. CONCLUSION: Infliximab represents an important
      advance in the treatment of rheumatoid arthritis, with tolerability concerns
      raised by early studies having been eased somewhat by more recent data in larger
      patient numbers. If preliminary results indicating that infliximab is able to
      arrest joint destruction in patients with rheumatoid arthritis are corroborated,
      the drug will likely become an integral component of future management strategies
      for this difficult-to-treat condition.

PMID- 10882168
TI  - Production and characterization of monoclonal IgM autoantibodies specific for the
      T-cell receptor.
AB  - Natural autoantibodies to the T-cell receptor (Tcr) have been identified in all
      human sera. However, titer, epitope specificity, and isotype vary with
      physiological conditions, autoimmune diseases, and retroviral infections. The
      levels of anti-Tcr autoantibodies in rheumatoid arthritis (RA) patients are
      significantly higher than in normal individuals, and the autoantibodies are
      typically IgM. To obtain detailed information on these autoantibodies, we
      generated B-cell heterohybridomas secreting monoclonal IgM autoantibodies (mAAbs)
      from the synovial tissue and peripheral blood of RA patients. We selected clones
      secreting mAAbs that bound a major Vbeta epitope defined by a synthetic peptide
      that contains the CDR1 region of the Vbeta 8.1 gene product. From these we
      isolated a subset of seven mAAbs that bound a recombinant single-chain
      Valpha/Vbeta construct containing the peptide epitope and, also to JURKAT cells
      which express Vbeta 8.1. The mAAbs produced by these clones were distinct from
      each other in their V-region sequences. However, all the V regions were
      essentially identical to germline sequences in both the heavy and light chains.
      Heavy-chain CDR3 segments ranged in length from 17 to 26 residues, did not
      correspond to any known autoantibodies, and showed extensive N-region diversity
      in the V(D)J junctions. Five monoclonal autoantibodies use VH 3 genes, while the
      remaining two utilized VH 4 sequences. Light-chain variable regions used were
      Vkappa3 (two), Vlambda3 (four), and one Vlambda2. These autoantibodies derived
      their unique features from their CDR3 segments that could not be aligned with any
      known sequences.

PMID- 10882169
TI  - Synthetic peptide mimics of a predicted topographical interaction surface: the
      cytochrome P450 2B1 recognition domain for NADPH-cytochrome P450 reductase.
AB  - In order to identify the cytochrome P450-binding domain for NADPH-cytochrome P450
      reductase, synthetic peptide mimics of predicted surface regions of rat
      cytochrome P450 2B 1 were constructed and evaluated for inhibition of the P450
      reductase interaction. A peptide corresponding to residues 116-134, which
      includes the C helix, completely inhibited reductase-mediated benzphetamine
      demethylation by purified P450 2B1. Replacement of Arg-125 by Glu yielded a
      noninhibitory peptide, suggesting that this residue significantly contributes to
      the reductase-P450 interaction. Additional P450 peptides were prepared which
      correspond to combinations of regions distant in primary sequence, but predicted
      to be spatially proximate. A peptide derived from segments of the C and L helices
      was a more potent inhibitor than peptides derived from either segment alone. This
      topographically designed peptide not only inhibited P450 2B1 in its purified
      form, but also when membrane-bound in rat liver microsomes. The peptide also
      inhibited microsomal aryl hydrocarbon hydroxylase, aniline hydroxylase, and
      erythromycin demethylase activities derived from other P450s. These results
      indicate that the C and L helices contribute to a reductase-binding site common
      to multiple P450s, and present a peptide mimic for this region that is useful for
      inhibition of P450-mediated microsomal activities.

PMID- 10882170
TI  - Specificity of cathepsin B to fluorescent substrates containing benzyl side-chain
      substituted amino acids at P1 subsite.
AB  - We have determined the kinetic parameters for the hydrolysis by cathepsin B of
      peptidyl-coumarin amide and intramolecularly quenched fluorogenic peptides with
      the general structures epsilonNH2-Cap-Leu-X-MCA and Abz-Lys-Leu-X-Phe-Ser-Lys-Gln
      EDDnp, respectively. Abz (orthoaminobenzoic acid) and EDDnp (2,4-dinitrophenyl
      ethylenediamine) are the fluorescent donor-acceptor pair, and X was Cys(SBzl),
      Ser(OBzl), and Thr(OBzl) containing benzyl group (Bzl) at the functional side
      chain of Cys, Ser, and Thr. The peptidyl-coumarin-containing Cys(SBz1),
      Ser(OBzl), and Thr(OBzl) have higher affinity cathepsin B, supporting the
      interpretation of the crystal structure of rat cathepsin B complexed with the
      inhibitor Z-Arg-Ser(OBzl)-CH2Cl that the benzyl group attached to Ser hydroxyl
      side chain occupies the enzyme S'(1) subsite [Jia et al. (1995), J. Biol. Chem.
      270, 5527]. A similar effect of benzyl group was also detected in the internally
      quenched peptides. Finally, the benzyl group in substrates containing Cys(SBzl)
      amino acid at P1 seems to compensate the absence of adequate S2-P2 interaction in
      the hydrolysis of the peptides having Pro or Ala at P2 position.

PMID- 10882171
TI  - Isolation and characterization of a cysteine protease from the latex of Araujia
      hortorum fruits.
AB  - A new protease (araujiain h I) was purified to mass spectroscopy homogeneity from
      the latex of Araujia hortorum Fourn. (Asclepiadaceae) fruits by
      ultracentrifugation and ion exchange chromatography. The enzyme has a molecular
      mass of 24,031 (mass spectrometry) and an iso-electric point higher than 9.3. The
      optimum pH range for casein hydrolysis was 8.0-9.5. The enzyme showed remarkable
      caseinolytic activity at high temperatures, although its thermal stability
      decayed rapidly. The proteinase was activated by thiol compounds and inhibited by
      common thiol-blocking reagents, particularly E-64 and HgCl2, suggesting the
      enzyme belongs to the cysteine protease family. The concentration of active sites
      as determined by titration with E-64 was 3.3 microM. When assayed on N-alpha-CBZ
      amino acid-p-nitrophenyl esters, the enzyme showed higher preference for the
      glutamine derivative, followed by those of alanine, asparagine, glycine, and
      leucine, in decreasing order. Partial homology (36-48%) with other plant cysteine
      proteinases was observed in an internal fragment obtained by Protease V8
      treatment.

PMID- 10882172
TI  - Arginine and ornithine oxidation catalyzed by lentil seedling copper-amine
      oxidase.
AB  - The oxidation of L-ornithine and L-arginine catalyzed by lentil (Lens esculenta)
      seedling copper-amine oxidase has been investigated by polarographic techniques,
      optical spectroscopy, and capillary electrophoresis. Both L-ornithine and L
      arginine were found to be poor substrates for lentil amine oxidase. L-Ornithine
      was oxidized to glutamate-5-semialdehyde and ammonia, in similar manner as usual
      substrates. Glutamate-5-semialdehyde spontaneously cyclizes to delta1-pyrroline-5
      carboxylic acid. Arginine is oxidized by an unusual mechanism yielding glutamate
      5-semialdehyde, ammonia, and urea as reaction products.

PMID- 10882173
TI  - A comparative study of human muscle and brain creatine kinases expressed in
      Escherichia coli.
AB  - We report the expression of the human muscle (CK-MM) and brain (CK-BB) creatine
      kinases in Escherichia coli. The proteins have been purified to apparent
      homogeneity and several of their physical and kinetic properties investigated. In
      the process, we have conclusively verified the correct DNA sequence of the genes
      encoding the respective isozymes, and determined the correct primary structure
      and mass of the gene products. Alignment of the primary sequences of these two
      enzymes shows 81% sequence identity with each other, and no obvious gross
      structural differences. However, Western blot analyses demonstrated the general
      lack of antigenic cross-reactivity between these isozymes. Preliminary kinetic
      analyses show the K(m) and k(cat) values for the creatine and MgATP substrates
      are similar to values reported for other isozymes from various tissues and
      organisms. The human muscle and brain CKs do not, however, exhibit the synergism
      of substrate binding that is observed, for example, in rabbit muscle creatine
      kinase.

PMID- 10882174
TI  - Molecular modeling of the complexes between Saccharomyces cerevisiae
      phosphoenolpyruvate carboxykinase and the ATP analogs pyridoxal 5'
      diphosphoadenosine and pyridoxal 5'-triphosphoadenosine. Specific labeling of
      lysine 290.
AB  - Molecular mechanics calculations have been employed to obtain models of the
      complexes between Saccharomyces cerevisiae phosphoenolpyruvate (PEP) kinase and
      the ATP analogs pyridoxal 5'-diphosphoadenosine (PLP-AMP) and pyridoxal 5'
      triphosphoadenosine (PLP-ADP), using the crystalline coordinates of the ATP
      pyruvate-Mn(2+)-Mg(2+) complex of Escherichia coli PEP carboxykinase [Tari et al.
      (1997), Nature Struct. Biol. 4, 990-994]. In these models, the preferred
      conformation of the pyridoxyl moiety of PLP-ADP and PLP-AMP was established
      through rotational barrier and simulated annealing procedures. Distances from the
      carbonyl-C of each analog to epsilon-N of active-site lysyl residues were
      calculated for the most stable enzyme-analog complex conformation, and it was
      found that the closest epsilon-N is that from Lys(290), thus predicting Schiff
      base formation between the corresponding carbonyl and amino groups. This
      prediction was experimentally verified through chemical modification of S.
      cerevisiae PEP carboxykinase with PLP-ADP and PLP-AMP. The results here described
      demonstrate the use of molecular modeling procedures when planning chemical
      modification of enzyme-active sites.

PMID- 10882175
TI  - Recent advances in the treatment of acute leukemia: 1999.
AB  - This review briefly summarizes literature noteworthy in the field of adult acute
      leukemia published during 1999. The relationship between specific cytogenetic
      abnormalities and response to treatment was explored within a clinical framework.
      In particular, detailed analyses of the abnormalities seen in acute promyelocytic
      leukemia were examined. Two case reports of special interest were published: one
      shed light on the role of histone deacetylase inhibitors in combination with all
      trans retinoic acid, and the other, on the role of granulocyte colony-stimulating
      factor in this disease. The clinical activity of arsenic was also reported and
      its mechanism of action explored. In acute lymphoblastic leukemia, attention was
      focused on occult translocations, and the importance of minimal residual disease
      was again emphasized. Lastly, results of early clinical trials using an anti-CD19
      antibody were reported, with provocative results.

PMID- 10882176
TI  - Detection of minimal residual disease in acute leukemia.
AB  - A significant proportion of patients with acute leukemia who achieve remission
      subsequently experience frank relapse of their disease, and their ultimate
      prognosis is typically poor. Although such disease recurrences have been
      impossible to predict using standard laboratory techniques, new methods have been
      studied that identify patients destined to relapse. Sensitive polymerase chain
      reaction analyses of unique breakpoint fusion regions, and, in cases of acute
      lymphoblastic leukemia, patient-specific gene rearrangements have been used to
      detect minimal residual disease. Multiparameter flow cytometry has also been used
      to identify rare leukemia cells among populations of predominantly normal cells.
      Because these types of studies in pediatric acute lymphoblastic leukemia have
      convincingly demonstrated that patients with evidence of minimal residual disease
      during remission have a much higher incidence of relapse, therapeutic protocols
      have been initiated that intensify therapy for patients with minimal residual
      disease detected during remission.

PMID- 10882177
TI  - Long term survivors of childhood leukemia.
AB  - Changes in therapy, primarily intensification, for childhood leukemias have
      significantly improved cure rates during the past 30 years. The increasing number
      of survivors has led to a heightened appreciation of the late complications of
      treatment caused by both radiation and chemotherapy. Important late effects
      include decreased growth, poor school performance, altered cardiac function,
      infertility, and second malignant neoplasms. The long term outcome of children
      and adolescents suffering from the most recently recognized acute complication of
      treatment, avascular necrosis of weight-bearing bones, is still not known. These,
      and all patients treated on clinical trials, should be followed throughout their
      lives. Many of the complications of treatment are often not realized until years
      after the completion of therapy; some have been found to be related to dose
      intensity, emphasizing the importance of clinical trials that examine reduction
      of therapy for diseases with excellent cure rates. A successful example of this
      strategy is the elimination or reduction of radiation dose for the prevention of
      central nervous system acute lymphocytic leukemia. This has resulted in fewer
      long term central nervous system complications without a decrease in survival
      rates. As knowledge of late effects increases, design of future trials will need
      to focus on striking a balance between cure and long term toxicity.

PMID- 10882178
TI  - Chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia continues to attract much basic and clinical
      research interest. Despite recent advances, the disease still has no established
      cure. Nonetheless, significant strides have been made in our understanding of the
      genetics, biology, and clinical staging of this disease. This understanding may
      improve our ability to segregate patients into subtypes that differ in their
      cytogenesis, propensity toward disease progression, or response to standard or
      innovative forms of therapy. Finally, several promising new modalities of
      treatment are being evaluated in clinical trials, involving novel drugs or drug
      combinations, monoclonal antibodies, stem cell transplantation, or gene therapy.

PMID- 10882179
TI  - Advances in the treatment of Hodgkin's lymphoma.
AB  - Given the successful treatment for most patients with Hodgkin's lymphoma, efforts
      have been directed primarily toward improving outcomes for the minority of
      patients with poor prognosis or relapsed disease or reducing the late effects of
      therapy for long-term survivors. Recently, a simple and clinically useful
      prognostic scoring system was developed for patients with advanced disease. This
      system allows better risk assessment for individual patients and more uniformity
      among patients participating in clinical trials. In addition, trials using newer
      chemotherapeutic regimens such as Stanford V or BEACOPP (bleomycin, etoposide,
      doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) are
      maturing with promising results. Other studies are helping to define the role of
      high-dose therapy for patients with Hodgkin's lymphoma, although biologic
      treatments such as cellular or antibody-based therapies are still in early phases
      of development. Lastly, positron emission tomographic scanning is emerging as a
      useful tool in staging and following Hodgkin's lymphoma.

PMID- 10882180
TI  - Recent advances in multiple myeloma.
AB  - Multiple myeloma is the second most common hematologic malignancy, with
      approximately 15,000 new cases each year in the United States. Our understanding
      of the pathophysiology underlying myeloma continues to expand, but the cause of
      this plasma cell dyscrasia remains unclear. Though controversy remains regarding
      a possible viral cause of myeloma, evidence suggesting a role for the human
      herpesvirus-8 is mounting. The roles of cytogenetic abnormalities as well as
      aberrant angiogenesis and cytokine expression in the etiology of myeloma continue
      to be explored and may lead to future therapeutic strategies. Transplantation in
      myeloma is rarely curative but offers clinical benefit not only for young but
      possibly for older myeloma patients as well. Newer bisphosphonates may offer
      greater ease of administration, improved efficacy, and possibly even enhanced
      antitumor effect. Finally, thalidomide offers significant clinical benefit to
      patients with myeloma previously refractory to multiple agents, and its role in
      early stages of the disease is under investigation.

PMID- 10882181
TI  - Advances in immunotherapy of hematologic malignancies: cellular and humoral
      approaches.
AB  - Monoclonal antibodies have become an important modality for cancer therapy.
      Genetically engineered chimeric and humanized antibodies have demonstrated
      activity against overt lymphoma and leukemia, as well as minimal residual
      disease. Radioimmunotherapy in both nonmyeloablative and myeloablative regimens
      has produced significant responses and also minimized radiation exposure to
      normal tissues. Targeted alpha-particle therapy offers the possibility of
      selective tumor cell kill. Antibody-drug conjugates have produced remissions in
      acute leukemia. Many proteins potentially act as leukemia or lymphoma-specific
      antigens for major histocompatibility complex-restricted T cell cytotoxicity.
      These include the idiotype proteins, breakpoint cluster region (bcr)-abl and
      other fusion oncoproteins, myeloid-specific differentiation antigens and minor
      histocompatibility antigens. Clinical trials exploiting the new understanding of
      the T cell immunology are underway.

PMID- 10882183
TI  - Bibliography. Current world literature. Hematologic malignancies.

PMID- 10882182
TI  - Supportive care in hematologic malignancies: hematopoietic growth factors,
      infections, transfusion therapy.
AB  - A number of recent developments in the supportive care of hematological
      malignancies have been selected for critical discussion. The first section
      focuses on the role of evidence-based guidelines in influencing the use of
      hematopoietic growth factors in medical practice. The next section updates the
      current clinical status of amifostine (Ethyol, Alza Corp., Palo Alto CA, USA, and
      US Bioscience, West Conshohocken, PA, USA) the first broad-spectrum
      cytoprotective agent available. The management of invasive fungal infections and
      the use of liposomal antifungal agents are reviewed next. Finally, the current
      status of transfusion support is presented.

PMID- 10882184
TI  - LDL-apheresis decreases plasma levels and urinary excretion of 8-epi-PGF2alpha.
AB  - Isoprostanes (IP) generated during free radical catalyzed oxidation injury have
      been claimed as a reliable indicator of oxidative stress in vivo. In particular,
      they are formed during LDL-oxidation. Vascular content, plasma levels and urinary
      excretion of IP were reported to be elevated in hypercholesterolemia. We
      therefore assessed the values of the IP 8-epi-PGF2alpha in plasma and urine in
      nine patients (7 males, 2 females) suffering from severe heterozygous
      hypercholesterolemia before and after LDL-apheresis as well as during the
      interval. LDL-apheresis caused a significant (P<0.01) drop in 8-epi-PGF2alpha in
      plasma and urine. The respective values in smokers (n = 4) were significantly
      (P<0.01) higher as compared to non-smokers. No sex difference was seen. Together
      with the findings of a parallel decrease in oxidized LDL, these data show a
      significant benefit of LDL-apheresis reducing in vivo oxidation injury. This
      benefit may at least partly contribute to the clinical improvement seen in the
      patients treated.

PMID- 10882185
TI  - The effects of glycation/glycoxidation on the liberation of 8-epi-PGF2alpha from
      low density lipoprotein during its in vitro oxidation.
AB  - In individuals suffering from diabetes mellitus, low-density lipoprotein (LDL)
      can undergo glycoxidation, both the surface protein and the unsaturated fatty
      acids in the particle core experiencing oxidative damage. In these patients,
      plasma levels of glycated(g)/glycoxidated(go) low-density lipoprotein and of 8
      epi-PGF2alpha (8-IP), a relatively stable peroxidation product of arachidonic
      acid, are increased. This study reports on the modified oxidation of gLDL and
      goLDL by human umbilical vein endothelial cells or by copper cations in the
      absence of cells. In both systems, glycated LDL was found to be more easily
      oxidized than either nLDL or goLDL. In addition, liberation of 8-IP from
      glycoxidated LDL is significantly reduced, because a large amount of 8-IP is
      already formed during long-term glycation of LDL in the absence of metal
      chelators, i.e. during glycoxidation. From these in vitro results we conclude,
      that 1) gLDL is more prone to cell-mediated oxidation than native or goLDL and 2)
      the increased in vivo plasma levels of 8-IP observed in diabetes mellitus could
      be due to prolonged LDL-glycoxidation liberating continuously significant amounts
      of 8-IP.

PMID- 10882187
TI  - Angiotensin II stimulates hypertrophic growth of cultured neonatal rat
      ventricular myocytes: roles of PKC and PGF2alpha.
AB  - Angiotensin II (Ang II) has been shown to regulate growth in smooth muscle cells.
      Protein kinase C (PKC), which mediates Ang II action, has been implicated in
      myocardial cell hypertrophy. Acute pressure overload in the left ventricles has
      been demonstrated to produce prostaglandin F2 alpha (PGF2alpha) release.
      Therefore, we used cultured neonatal rat ventricular myocytes to study Ang II,
      PKC and PGF2alpha and their relationship to hypertrophy. The amount of PGF2alpha
      produced was determined by radioimmunoassay, Ang II-induced hypertrophy and
      PGF2alpha release. Pretreatment with 10(-6) M of PKC inhibitor, 1-(5
      isoquinolinesulfonyl-methyl) piperazine (H7), blocked Ang II-induced hypertrophy
      and PGF2alpha release. In neonatal rat ventricular myocytes that were treated
      with either Ang II or PKC activator (Phorbol 12, 13, dibutyrate; PDBu), PKC
      enzyme assay showed PKC was translocated from the cytosol to the membrane which
      indicates activation. This suggests that PKC mediates, in part, Ang II-induced
      PGF2alpha release and hypertrophy. In summary, Ang II activates PKC, which causes
      PGF2alpha release and hypertrophy, and this PGF2alpha release and hypertrophy can
      be overcome by pretreatment with PKC inhibitor.

PMID- 10882186
TI  - Changes in sphingolipid levels induced by epidermal growth factor in osteoblastic
      cells. Effects of these metabolites on cytosolic calcium levels.
AB  - Sphingolipids mediate a number of cellular functions in a variety of cell
      systems. The role they play in osteoblast signaling is yet unknown. This study
      investigated the effects of epidermal growth factor (EGF) on the levels of
      ceramide, sphingosine (SPH), and sphingosine-1-phosphate (S1P) in rat calvariae
      osteoblastic cells, and whether these metabolites mediated cytosolic calcium
      ([Ca2+]i) mobilization in these cells. EGF significantly (P<0.05) increased the
      levels of all three sphingolipids, and the phorbol ester PMA partially inhibited
      these effects. SPH and S1P markedly increased [Ca2+]i levels, with thapsigargin
      (depletes [Ca2+]i pools) decreasing the response by 60%. Verapamil (calcium
      channel blocker) only inhibited ceramide's effects on [Ca2+]i. Furthermore, SPH
      enhanced the EGF' induced increase in [Ca2+]i. This study demonstrates that
      ceramide, SPH and S1P mediate [Ca2+]i mobilization in rat calvarial osteoblastic
      cells, and that EGF induces changes in the levels of these metabolites with PKC
      playing an important role in the mechanisms regulating these events.

PMID- 10882188
TI  - Nitric oxide inhibits prostanoid synthesis in the rat oviduct.
AB  - We have studied the effect of nitric oxide (NO) on the production of arachidonic
      acid ([14C]-AA) metabolites in the rat oviduct. The basal synthesis of
      eicosanoids was measured by the conversion of ([14C]-AA) to the different
      radiolabeled products of cyclooxygenase (COX). The oviducts incubated for 1 h
      with the labeled substrate of COX were able to convert 3.3 +/- 0.3% of ([14C]-AA)
      to 6-ceto-PGF1alpha, 10.7 +/- 1.0% to PGF2alpha, 13.5 +/- 1.2% to PGE2 and 6.3 +/
      0.5% to TXB2. The tissues were incubated with different doses of two NO donors:
      SIN-1 and Spermine NONOate. The results indicated that SIN-1 produces a
      significant decrease (50%; P < 0.05) in all prostanoids evaluated in a dose
      response fashion. The inhibitory effect was completely reversed by addition of 20
      microg/ml of hemoglobin (Hb), a NO scavenger. The addition of Spermine NONOate to
      the incubation medium diminished significantly (65%) the synthesis of COX
      metabolites suggesting that NO acts by inhibiting COX activity in the rat
      oviduct. However, NOS inhibitors, N(G)-L-arginine-methyl-ester (L-NAME) nd N(G)-L
      monomethyl-arginine (L-NMMA) had no effect on basal production of the
      prostanoids. These results indicate that in the rat oviduct the synthesis of COX
      metabolites is negatively regulated by nitric oxide.

PMID- 10882189
TI  - IL1alpha augments prostaglandin synthesis in pregnant rat uteri by a nitric oxide
      mediated mechanism.
AB  - This study aims to examine the possible relationship between cytokines, nitric
      oxide (NO) and prostaglandins in the pregnant rat uterus. Results indicate that
      1) IL1alpha enhances the synthesis of prostaglandins and augments NO production
      in pregnant rat uteri and 2) the effect of IL1alpha on prostaglandin synthesis is
      abolished by NMMA, a NOS inhibitor, by aminoguanidine, an iNOS inhibitor, and by
      NS-398, a COX-2 inhibitor. These results suggest that there is an interaction
      between IL1alpha, NO and prostaglandins and that are involved COX-2 and iNOS in
      this interrelationship. This mechanism might be important in the regulation of
      uterine contractility during pregnancy and labor.

PMID- 10882190
TI  - Effects of long-chain fatty acids on human urothelial cells in organ culture.
AB  - It has been suggested that tumour-derived cells are differentially sensitive to
      the anti-proliferative and cytotoxic effects of long chain n-3 and n-6
      polyunsaturated fatty acids (PuFAs). We have previously shown that PuFAs are also
      growth suppressive to highly proliferative normal human urinary bladder uro
      epithelial (NHU) cells grown in monolayer culture. To determine if the effects on
      NHU cells are directly related to the proliferative index, we have studied the
      effects of long chain fatty acids in a bladder organ culture system, where
      proliferation and differentiation of the urothelium is under homeostatic control.
      A 50 microM concentration of fatty acids was chosen as this concentration of PuFA
      was profoundly growth inhibitory to NHU cells in monolayer culture. In organ
      culture, 50 microM PuFAs had no detectable effect on the proliferation or on the
      preservation of urothelial differentiated histioarchitecture, as assessed using a
      panel of phenotypic markers. These results suggest that the effects of PuFA may
      be modulated by the tissue microenvironment.

PMID- 10882191
TI  - Effect of allicin from garlic powder on serum lipids and blood pressure in rats
      fed with a high cholesterol diet.
AB  - The use of fresh aqueous garlic extract is known to be effective in reducing
      thromboxane formation by platelets in both in vivo and in vitro animal models of
      thrombosis. In the present study, we studied the effect of Lichtwer garlic powder
      (containing 1.3% alliin equivalent to 0.6% allicin) on the serum cholesterol,
      triglyceride, glucose, protein, and systolic blood pressure in rats fed with a
      high cholesterol diet. Experimental rats were fed a 2% high cholesterol diet with
      and without garlic powder for 6 weeks. Control rats were fed a normal diet. The
      aqueous garlic powder extract was given orally to rats on a daily basis. It was
      observed that cholesterol-fed animals had a significant increase in serum
      cholesterol compared to the control group of rats fed on a normal diet. However,
      when the rats were fed with a high cholesterol diet mixed with garlic powder,
      there was a significant reduction in their serum cholesterol levels compared with
      the group which were on a diet containing high cholesterol without garlic powder.
      Serum triglyceride levels were also significantly lowered by garlic powder when
      compared to control and high cholesterol diet group rats. The blood pressure of
      the high cholesterol diet animals was significantly higher compared to the
      animals receiving the control diet. The blood pressure of the animals receiving
      garlic powder and high cholesterol diet was significantly lower as compared to
      the high cholesterol and control diet group. No significant changes were observed
      in the serum glucose and protein in all of the rats. These results show that
      garlic is beneficial in reducing blood cholesterol, triglycerides levels and
      systolic blood pressure in hypercholesterolemic rats. Our experimental results
      show that garlic may beneficially affect two risk factors for atherosclerosis-
      hyperlipidemia and hypertension.

PMID- 10882192
TI  - Regulation of cyclooxygenase and 12-lipoxygenase catalysis by phospholipid
      hydroperoxide glutathione peroxidase in A431 cells.
AB  - Regulation of arachidonate metabolism in human epidermoid carcinoma A431 cells by
      phospholipid hydroperoxide glutathione peroxidase (PHGPx) and cytosolic
      glutathione peroxidase (GPx1) was studied. In order to study the effect of
      reduced glutathione (GSH) on the catalysis regulation of these oxygenation
      enzymes, diethyl maleate was used to deplete the intracellular GSH. In the
      presence of 13-hydroperoxyoctadecadienoic acid, the enzymatic catalysis of
      cyclooxygenase and 12-lipoxygenase was significantly increased in the GSH
      depleted cells. In terms of the inhibitory effect on 12-lipoxygenase, PHGPx was
      more sensitive to GSH concentrations than GPx1. Inhibition of PHGPx activity by
      the treatment of cells with antisense oligonucleotide of PHGPx mRNA increased the
      enzymatic catalysis of both cyclooxygenase and 12-lipoxygenase. In conclusion,
      the results indicate that catalysis of cyclooxygenase and 12-lipoxygenase in A431
      cells was regulated by redox-reaction, and PHGPx seems to play an important role
      in the controlling of these reactions.

PMID- 10882193
TI  - Solid-state nuclear magnetic resonance.

PMID- 10882194
TI  - Planar chromatography.

PMID- 10882196
TI  - Column liquid chromatography: equipment and instrumentation

PMID- 10882195
TI  - Thermal analysis

PMID- 10882197
TI  - Kinetic determinations and some kinetic aspects of analytical chemistry

PMID- 10882198
TI  - Infrared spectroscopy.

PMID- 10882199
TI  - Fiber-optic chemical sensors and biosensors.

PMID- 10882201
TI  - Surface analysis: X-ray photoelectron spectroscopy and Auger electron
      spectroscopy

PMID- 10882200
TI  - Chemometrics

PMID- 10882203
TI  - Supercritical fluid and unified chromatography

PMID- 10882202
TI  - Capillary electrophoresis for the analysis of biopolymers.

PMID- 10882204
TI  - Gas chromatography.

PMID- 10882206
TI  - Electrothermal atomic absorption spectrometry and related techniques

PMID- 10882207
TI  - Chemical microscopy.

PMID- 10882205
TI  - Raman spectroscopy.

PMID- 10882208
TI  - Scanning probe microscopy.

PMID- 10882209
TI  - Molecular fluorescence, phosphorescence, and chemiluminescence spectrometry.

PMID- 10882210
TI  - X-ray spectrometry

PMID- 10882211
TI  - Systemic sclerosis (scleroderma) and related disorders: clinical aspects.
AB  - To adequately evaluate and manage patients with systemic sclerosis, practitioners
      and patients alike must have a working knowledge of the natural history of the
      disease. What we know generally about the natural history should be coupled with
      four pieces of patient specific clinical information. (i) Does the patient have
      systemic sclerosis? (ii) How long has the patient had systemic sclerosis? (iii)
      How extensive was/is the sclerodermatous skin induration/ thickening at its
      worst? (iv) Is there presently evidence of visceral involvement (heart, lung,
      kidney, gastrointestinal, musculoskeletal)? This chapter will show you how to use
      this information to construct (for you and the patient) a picture of where that
      patient is presently in the natural history, where the patient is likely to be in
      the future (in general terms), what visceral involvements are likely or unlikely
      to occur, what evaluations are needed now and in the future, and what treatments
      are recommended and why.

PMID- 10882212
TI  - Scleroderma and related disorders: therapeutic aspects.
AB  - Improvements in management of systemic sclerosis have occurred through a growing
      understanding of pathogenic events accompanied by advances in diagnosis and
      assessment, as well as developments in organ-based therapeutics. Unfortunately,
      disease-modifying therapies of proven efficacy remain elusive and several agents
      in current use have been shown in well-controlled clinical trials to be of
      questionable benefit. More positively, there have been advances in the treatment
      of major visceral complications such as renal crisis, pulmonary fibrosis,
      pulmonary hypertension, gastrointestinal involvement and in the management of
      scleroderma-associated Raynaud's phenomenon. Current approaches are reviewed,
      evidence supporting or refuting the use of putative disease-modifying agents is
      discussed, and new strategies are described that are currently being considered
      for this fascinating but complex multisystem connective tissue disease.

PMID- 10882213
TI  - Idiopathic inflammatory muscle disease: clinical aspects.
AB  - Although much remains to be learned about the immune-mediated myositis syndromes,
      information generated from recent studies in a number of areas may assist
      physicians in patient management. Topics reviewed here include: data supporting
      the association of myositis with cancer and the appropriate evaluations for
      malignancy in a myositis patient; an approach to the assessment of patients with
      dermatomyositis sine myositis; the usefulness of the clinicopathological and
      serological classifications; a discussion of whether childhood and adult myositis
      are the same or different entities; a review of those prognostic factors to
      consider in the clinical management of myositis patients; current approaches and
      their limitations for assessing disease activity and damage. To improve our
      limited understanding of the myositis syndromes, national and international
      collaborations are needed to obtain the necessary numbers of subjects, given the
      rarity and heterogeneity of these disorders.

PMID- 10882214
TI  - Inflammatory muscle disease: therapeutic aspects.
AB  - The present treatment of the inflammatory myopathies remains unsatisfactory in
      several areas, perhaps due in part to our incomplete knowledge of their
      aetiology. These conditions have been grouped together for practical purposes and
      because of a similar approach to treatment. However, recent data regarding
      pathological findings, serological patterns and different outcomes, suggest that
      some of these myopathies may be distinct, and perhaps approaches to treatment
      should be tailored according to these findings. This chapter will attempt to
      update our current management, offer an analysis of recent data regarding newer
      treatment modalities and highlight areas lacking solid data that need to be
      further addressed. Although corticosteroids are still considered to be the
      mainstay of treatment, the earlier use of immunosuppressive therapy will be
      discussed, as will the use of autoantibody profiles for tailoring treatment.
      Newer modalities for the monitoring of therapeutic response and their current
      place in clinical practice will be analysed. The management of refractory cases
      will be addressed as will the current management of calcinosis, a problem more
      frequently encountered in children.

PMID- 10882215
TI  - Sjogren's syndrome: autoimmune epithelitis.
AB  - Sjogren's syndrome (SS) is a chronic autoimmune disorder of the exocrine glands
      of unknown aetiology, which is typically associated with focal lymphocytic
      infiltrates of glandular tissues and autoantibody responses against the Ro(SSA)
      and La(SSB) ribonucleoproteins. In almost one-third of patients disease involves
      various extraglandular sites, whereas approximately 5% of patients may also
      develop malignant B-cell lymphoma. In addition, features of SS are frequently
      encountered (5-20%) in patients with several other autoimmune rheumatic diseases,
      and in several respects these 'secondary' forms may be distinct from SS found
      alone (primary-SS), as well as from each other. The correct diagnosis and
      management of SS may require consideration from various specialists. Differential
      diagnosis includes adverse effects of drugs, sarcoidosis, lipoproteinaemias, age
      related atrophy, chronic graft-versus-host disease, lymphomas, amyloidosis and
      infection by human immunodeficiency virus or hepatitis C virus. Based on the
      sequential application of the validated European classification criteria for SS,
      a practical algorithm for diagnosis is presented. Despite progress in the
      understanding of the broad clinicopathological spectrum of the entity, its
      treatment remains largely empirical and symptomatic. To date, the decision for
      systemic therapeutic intervention is primarily based on the severity of
      extraglandular manifestations.

PMID- 10882216
TI  - Relapsing polychondritis.
AB  - Relapsing polychondritis is a rare inflammatory disease of unknown aetiology
      characterized by recurrent inflammation and destruction of cartilaginous
      structures and connective tissue. Current data provide increasing support for an
      autoimmune basis, but its cause remains unknown. Individuals of any race, gender,
      or age may be affected, but it is most commonly seen between the ages of 40 and
      60 years. Although relapsing polychondritis occurs predominantly as a separately
      defined clinical complex, a significant number of patients may suffer from
      another underlying rheumatic and/or haematological disorder; vasculitic syndromes
      are the most commonly observed disorders associated with relapsing
      polychondritis. Common clinical features are auricular, nasal and respiratory
      tract chondritis with involvement of organs of special sense, such as the eyes
      and audiovestibular apparatus. Polyarthritis and vasculitic involvement are also
      common. Corticosteroids are still the agents of choice although several other
      anti-inflammatory drugs can be used in order to allow tapering of the steroid
      dose or to achieve a lower maintenance dose for refractory cases.

PMID- 10882217
TI  - Mixed connective tissue disease: overlap syndromes.
AB  - Since the original description of mixed connective tissue disease (MCTD) as an
      apparently unique syndrome by Sharp and co-workers, the concept of MCTD has been
      highly controversial. In this chapter, a quarter of a decade later, we examine
      the evidence that MCTD is a distinctive entity rather than a haphazard
      association of clinical and serological features and that the presence of high
      titres of autoantibodies to UIRNP influences the expression of connective tissue
      disease in ways that are relevant to prognosis and treatment. Results of longterm
      clinical studies are presented, which show that the clinical phenotype of MCTD is
      robust and can be defined by classification criteria that show reasonable
      sensitivity and specificity. In addition, the chapter addresses the results of
      immunogenetic and serological studies that demonstrate that MCTD is quite
      distinctive from systemic lupus erythematosus and systemic sclerosis. Indeed,
      there is good evidence that the clinical and serological features of MCTD are not
      just a haphazard association but that these patients represent a distinctive
      subset of connective tissue disease in which the specific autoimmune response is
      relevant to clinical expression and to understanding the underlying pathogenesis.

PMID- 10882218
TI  - Unclassified or undifferentiated connective tissue disease.
AB  - This chapter deals primarily with the evidence available regarding the use of the
      term unclassified or undifferentiated connective tissue disorders (CTDs) to refer
      to patients with manifestations suggestive, but not diagnostic, of either defined
      CTDs, a well-defined overlap syndrome (manifestations and criteria for two or
      more CTDs), or mixed CTD (MCTD). Possible outcomes for these patients include
      remaining undifferentiated, differentiating into a defined CTD or going into
      remission. MCTD and atypical CTD (term used by the parties involved in the
      'Silicone breast implant' controversy) are only briefly discussed.

PMID- 10882219
TI  - The anti-phospholipid antibody syndrome: clinical and serological aspects.
AB  - The association of thromboses and/or cytopenias with anti-phospholipid antibodies
      (aPL), the anti-phospholipid syndrome (APS), is well recognized. The syndrome may
      be primary or occur within systemic lupus erythematosus (SLE). The notion of the
      syndrome occurring within SLE is important since patients found to have aPL may
      be at risk for developing APS manifestations, those who develop some
      manifestations may be at risk for developing others and, finally, SLE patients
      with this syndrome may need special treatment. There are subtle differences
      between the primary and the secondary forms, mostly due to the frequently higher
      and more persistent autoantibody levels in the primary and the influence of lupus
      in the secondary. These syndromes may be related to various antigen/antibody
      systems in which phospholipids participate either directly or through their
      effect on the proteins that bind them. Similar clinical manifestations also occur
      in patients who have serum antibodies to such proteins (e.g. beta2-glycoprotein
      I) in the absence of phospholipid. Some of these antibodies may even be more
      important pathogenically than the antibodies against cardiolipin that were
      originally described. Testing for the latter is, however, still the first choice
      when suspecting an antiphospholipid syndrome. If this is negative in this
      situation, a search for the other autoantibodies is indicated.

PMID- 10882220
TI  - The anti-phospholipid antibody syndrome (Hughes syndrome): therapeutic aspects.
AB  - Despite the enormous amount of work focused on the pathogenesis and clinical
      manifestations of the Hughes or anti-phospholipid syndrome (APS), there is little
      published on management. Usually, the diagnosis of APS is made after the first
      thrombotic event, when a thrombophilia screen is performed. These patients have a
      high risk of recurrent thromboses and current therapy centres on the use of
      thromboprophylaxis with warfarin. However, a number of clinical questions keep
      recurring: do arterial and venous thrombosis require the same intensity of anti
      coagulation? When should warfarin be stopped? Should patients who develop
      thrombosis when other risk factors (oral contraceptive pill, prolonged resting
      etc.) are present be treated like those without any risk factors but the presence
      of anti-phospholipid antibodies (aPL)? How to manage a patient with recurrent
      thrombosis despite a high intensity anti-coagulation (International normalized
      ratio (INR) between 3.0-4.0)? Since many of the patients with aPL are fertile
      women, a substantial group of patients are diagnosed after recurrent pregnancy
      loss. Low-dose aspirin for those patients without previous thrombosis and aspirin
      plus heparin for patients with a history of thrombotic events are the current
      therapeutic options. However, some questions remain unanswered: does the addition
      of heparin to low-dose aspirin in women with first trimester recurrent
      miscarriage but without previous thrombosis improve foetal outcome over and above
      aspirin alone? Which is the best therapeutic regime during pregnancy for patients
      with aPL-associated stroke? When should high-dose intravenous gammaglobulin be
      considered? Finally, very little is known about the risk of thrombosis in
      individuals positive for aPL but still free of thrombosis. Should these
      individuals receive any treatment? If so, which one? In this review we attempt to
      address some of these questions taking into account available data from
      retrospective and prospective studies and our own clinical experience.

PMID- 10882221
TI  - Immunologic orchestration of hypersensitivity pneumonitis.

PMID- 10882222
TI  - Heart-hitting tales of salt and destruction.

PMID- 10882223
TI  - Insights into modulation of (and by) growth hormone signaling.

PMID- 10882224
TI  - Inhalation of nitric oxide in acute respiratory distress syndrome.

PMID- 10882225
TI  - Mediators of hypersensitivity pneumonitis.
AB  - Inhalation of Saccharopolyspora rectivirgula (S. rectivirgula) causes farmer's
      lung disease, a classic example of hypersensitivity pneumonitis (HP). HP is
      characterized by bronchoalveolar lavage fluid (BALF) neutrophilia (within the
      first 48 hours after inhalation), followed by BALF lymphocytosis. We utilized a
      well-described murine model of HP to determine the timing of the appearance of
      the C-C chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage
      inflammatory protein-1alpha (MIP-1alpha); the inflammatory cytokines tumor
      necrosis factor (TNF), interleukin-1alpha (IL-1alpha), and interleukin-6 (IL-6);
      and the Th1 -differentiating cytokine interleukin-12 (IL-12) in BALF. After a
      single intratracheal administration of S. rectivirgula, there was remarkable BALF
      neutrophilia (peak 24 to 48 hours), followed by a BALF lymphocytosis (peak 48 to
      72 hours) in both C57Bl/6 and BALB/c mice that was preceded by the appearance of
      MIP-1alpha in BALF (peak 4 to 6 hours) and MCP-1 (peak at 48 hours). In both
      strains of mice there was a striking increase of BALF IL-12 (peak 48 to 72
      hours). There was also an increase in BALF IL-6, IL-1alpha, and TNF that was
      greater in the BALB/c mice than in the C57Bl/6 mice. S. rectivirgula induced the
      secretion of MIP-1alpha, MCP-1, IL-6, IL-1alpha, and IL-12 from the murine
      macrophage cell line J774A.1; MIP-1alpha, IL-6, IL-1alpha, IL-12, and TNF from
      C57Bl/6 alveolar macrophages; and IL-1alpha, IL-6, and TNF-but not IL-12-from
      BALB/c alveolar macrophages. We conclude that chemokines and cytokines induced by
      intratracheal administration of S. rectivirgula precede BALF neutrophilia and
      lymphocytosis and may cause differentiation of Th1 cells; we also conclude that
      pulmonary macrophages represent a potential source of these substances.

PMID- 10882226
TI  - Induced sputum and bronchoalveolar lavage as tools for evaluating the effects of
      inhaled corticosteroids in patients with asthma.
AB  - Changes in airway inflammation can be studied with bronchoalveolar lavage, but
      the widespread use of this procedure is limited by its invasiveness. The aim of
      this study was to evaluate the usefulness of induced sputum as a non-invasive
      alternative to bronchoalveolar lavage for studying changes in airway inflammation
      in patients with asthma. Thirty patients were treated for 12 weeks with an
      inhaled corticosteroid (fluticasone propionate (FP), 250 microg twice daily) or a
      short-acting beta-agonist (salbutamol (Sb), 400 microg twice daily) in a double
      blind, double-dummy, randomized parallel group study. Sputum induction with
      hypertonic saline solution was performed twice before treatment and after 4, 8,
      10, and 11 weeks of treatment. Bronchoalveolar lavage fluid divided into two
      pools (first 60 mL portion as bronchoalveolar lavage/bronchial wash (BAL/BW) and
      subsequent 80 mL as bronchoalveoalar lavage (BAL)) was obtained before and after
      12 weeks of treatment. Changes in cell differentials and plasma-protein leakage
      (alpha2-macroglobulin, albumin, and their ratio (relative coefficient of
      excretion, RCE)) were analyzed in induced sputum and were compared with changes
      in BAL/BW and BAL. During treatment with FP, the PC20histamine (interpolated
      concentration of histamine that caused a fall in FEV1 of 20% of the baseline
      value) increased (P < .0001), and the percentage of eosinophils (P = .004),
      levels of (alpha2-macroglobulin (P = .09) and RCE (P = .007) decreased in sputum.
      These changes were different from those in the Sb group (PC20histamine P< .0001,
      eosinophils P= .004, alpha2-macroglobulin P= .003, RCE P = .01), in which alpha2
      macroglobulin showed a significant increase (P = .015). Changes in the percentage
      of eosinophils and in the levels of alpha2-macroglobulin in sputum were
      associated with changes in the PC20histamine (Rs = -0.59, P = .007 and Rs = 
      0.47, P = .03, respectively). These correlations did not reach significance in
      BAL/BW and BAL fluid. The statistical power to detect changes in induced sputum
      was higher for the percentage of eosinophils and similar for plasma protein
      leakage as compared with analysis of BAL/BW and BAL fluid. We conclude that the
      analysis of induced sputum is a useful, non-invasive alternative to
      bronchoalveolar lavage for assessing the effects of antiinflammatory drugs in
      asthma.

PMID- 10882227
TI  - Effect of rebamipide on prostaglandin EP4 receptor gene expression in rat gastric
      mucosa.
AB  - Prostaglandin E2 (PGE2) plays an important role in the regulation of gastric
      mucus secretion. We have previously shown that the prostaglandin EP4 receptor
      (EP4) gene is abundantly expressed in gastric mucus-producing cells. Furthermore,
      we have shown that EP4 is present in a rat normal gastric mucosal cell line
      (RGM1) and that PGE2 increases mucus secretion from these cells via EP4.
      Rebamipide, an anti-gastric ulcer agent, has been reported to promote gastric
      PGE2 production and mucus secretion. However, it is unclear whether rebamipide
      influences mucus secretion by altering expression of the EP4 gene. Therefore, we
      tested the effect of rebamipide on EP4 gene expression in the gastric mucosa.
      Seven-week-old Wistar rats received oral rebamipide (100 mg/kg) with and without
      water-immersion restraint stress (WRS). All rats were killed, and their gastric
      tissues were used to investigate the expression of mRNA for EP4 and
      cyclooxygenase types 1 and 2. The thickness of the gastric mucus layer was also
      measured. The effect of rebamipide on EP4 gene expression and PGE2 production in
      RGM1 cells was also investigated in vitro. Furthermore, the effect of PGE2 on
      cyclic adenosine monophosphate (cAMP) production by RGM1 cells with or without
      rebamipide was studied. Oral rebami-pide significantly increased EP4 gene
      expression in the gastric antrum but not in the corpus after WRS. Furthermore, it
      increased surface mucus thickness and suppressed ulcer formation in the gastric
      mucosa after WRS. In vitro, rebamipide significantly augmented EP4 gene
      expression in RGM1 cells, and PGE2 significantly increased the cAMP production by
      RGM1 cells incubated with rebamipide. Rebamipide promotes EP4 gene expression and
      may consequently increase the gastric mucus secretion via EP4 receptors in the
      rat antral mucosa.

PMID- 10882228
TI  - Physiologic concentrations of homocysteine inhibit the human plasma GSH
      peroxidase that reduces organic hydroperoxides.
AB  - The plasma reduced glutathione (GSH) selenoperoxidase is a highly conserved
      enzyme. Furthermore, a small clinical study reported that patients with severe
      atherosclerosis had low peroxidase activities. Together these observations
      suggest that the peroxidase is important in preventing atherosclerosis. Yet
      others have reported that when the assay was run in Tris buffer, it was inactive
      with the concentrations of GSH found in the plasma. Second, it is known that
      hyperhomocysteinemia increases the rate of atherogenesis. Because there is some
      homology between homocysteine and the cysteine in GSH, the question is whether
      the hyperhomocysteinemia effect may be due to inhibition of the peroxidase. We
      purified the peroxidase from human plasma and determined its activity by a
      coupled spectrophotometric assay and a substrate disappearance chemiluminescence
      assay. When the peroxidase activity was determined in phosphate-buffered saline
      solution (PBS), there was significant activity with the reported plasma GSH
      concentrations (5 to 20 micromol/L). The peroxidase was exclusively in the HDL
      fraction. There was no correlation between the peroxidase activity and the HDL or
      LDL cholesterol concentrations. Finally, at physiologic concentrations of GSH (9
      micromol/L), the peroxidase was inhibited by physiologic, free homocysteine
      concentrations (1 to 5 micromol/L). These data suggest that the peroxidase is
      active in vivo and may be important in protecting the endothelium from
      atherosclerosis by preventing oxidant injury. The homocysteine inhibition of the
      peroxidase suggests a possible biochemical basis for the observed association
      between hyperhomocysteinemia and cardiovascular disease. Our studies imply that
      low concentrations of this peroxidase may be an independent risk factor for
      atherosclerosis.

PMID- 10882229
TI  - Regulation of Candida albicans growth and adhesion by saliva.
AB  - To examine the local regulation of oral Candida albicans growth, we examined non
      stimulated and stimulated salivary flow rates (SFRs) and the C. albicans growth
      and adhesion inhibitory activities of saliva in 60 patients with oral candidiasis
      (divided into two groups: 25 patients with oral candidiasis only (group OC) and
      35 patients with oral candidiasis and systemic diseases (group CS)) and 30
      healthy control subjects. Both non-stimulated and stimulated SFRs in patients,
      especially in group CS; were decreased in comparison with those in the healthy
      control subjects. The levels of secretory immunoglobulin A (sIgA) in group OC and
      group CS and the lactoferrin level in group CS were decreased as compared with
      those in control individuals, although there were no differences in transferrin
      and total secretory component (SC) levels between the three groups. The secretion
      amounts (microg/min) of these proteins were statistically significantly decreased
      in the patients, especially in group CS. Saliva from the patients showed a lesser
      inhibitory effect on C. albicans growth and adhesion to HeLa cells than did
      saliva from the control subjects. In addition, polymorphonuclear leukocytes
      (PMNs) in patients' saliva generated smaller amounts of superoxide than did those
      in control subjects' saliva, and phagocytic and C. albicans killing activities
      were suppressed in the patients. These results indicate that the decreases in
      SFR, secretion of antimicrobial proteins in saliva, and salivary PMN activity are
      risk factors for oral candidiasis associated with aging and systemic diseases.

PMID- 10882230
TI  - Heparin neutralization is essential for accurate measurement of factor VIII
      activity and inhibitor assays in blood samples drawn from implanted venous access
      devices.
AB  - The purpose of this study was to determine the prevalence and effect of heparin
      contamination in samples drawn from implanted venous access devices (VADs, ports)
      on factor VIII activity and Bethesda inhibitor assay (BU) and the efficacy of
      heparinase to neutralize heparin. Plasma samples containing 85, 45, and 2 U/dL
      factor VIII were spiked in vitro with heparin from 0 to 3 U/mL. Factor VIII
      activity was assayed with a one-stage clotting assay on paired samples before and
      after heparinase, 25 mg/mL plasma. Paired patient samples drawn from VADs were
      assayed for heparin concentration, factor VIII, and BU before and after
      heparinase. At all three concentrations of factor VIII in vitro, the addition of
      heparin at 0.12 to 0.25 U/mL decreased assayed factor VIII activity. Heparinase
      neutralized up to 2 U/mL heparin and resulted in accurate factor VIII
      determination. Of 105 VAD samples, 47 (45%) had heparin contamination >0.05 U/mL.
      Of 47 heparin-contaminated samples, 42 showed decreased factor VIII activity in
      before/after comparisons. False-positive BU results were detected in 6 of 47
      heparin-contaminated samples. Heparin contamination occurs frequently in samples
      drawn from VADs and could increase costs through excessive factor concentrate
      use. We recommend that all VAD samples be pretreated with heparinase before the
      assay of factor VIII activity or Bethesda inhibitor titers.

PMID- 10882231
TI  - Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and characterization.
AB  - The imidazoline-1 receptor (IR1) is considered a novel target for drug discovery.
      Toward cloning an IR1, a truncated cDNA clone was isolated from a human
      hippocampal lambda gt11 cDNA expression library by relying on the selectivity of
      two antisera directed against candidate IR proteins. Amplification reactions were
      performed to extend the 5' and 3' ends of this cDNA, followed by end-to-end PCR
      and conventional cloning. The resultant 5131-basepair molecule, designated
      imidazoline receptor-antisera-selected (IRAS) cDNA, was shown to encode a 1504
      amino acid protein (IRAS-1). No relation exists between the amino acid sequence
      of IRAS-1 and proteins known to bind imidazolines (e.g., it is not an alpha2
      adrenoceptor or monoamine oxidase subtype). However, certain sequences within
      IRAS-1 are consistent with signaling motifs found in cytokine receptors, as
      previously suggested for an IR1. An acidic region in IRAS-1 having an amino acid
      sequence nearly identical to that of ryanodine receptors led to the demonstration
      that ruthenium red, a dye that binds the acidic region in ryanodine receptors,
      also stained IRAS-1 as a 167-kD band on SDS gels and inhibited radioligand
      binding of native I1 sites in untransfected PC-12 cells (a source of authentic I1
      binding sites). Two epitope-selective antisera were also generated against IRAS
      1, and both reacted with the same 167-kD band on Western blots. In a host-cell
      specific manner, transfection of IRAS cDNA into Chinese hamster ovary cells led
      to high-affinity I1 binding sites by criteria of nanomolar affinity for
      moxonidine and rilmenidine. Thus, IRAS-1 is the first protein discovered with
      characteristics of an IR1.

PMID- 10882232
TI  - Genomic organization of the human and mouse stau genes.
AB  - Mammalian Staufen is a double-stranded RNA-binding protein potentially involved
      in mRNA transport and localization. Recently, we reported that the human gene is
      located on chromosome 20, region q13.1. We now report the genomic organization of
      both the human and mouse stau genes. Amplification of genomic DNA and sequencing
      of the resulting PCR products indicated that the human and mouse genes are
      fragmented into 15 and 12 exons, distributed over at least 65 and 17 kb of
      genomic DNA, respectively. The three additional exons found in the human gene are
      subjected to differential splicing, generating four different transcripts.
      Corresponding exons have not been found in mouse transcripts. Apart from those
      three exons, the overall organization of the stau gene is similar in the two
      species, and the positions of the exon-intron junctions are perfectly conserved.
      Even an alternative choice between two splicing acceptor sites, which causes an
      insertion of 18 nucleotides in exon 5, is conserved in both humans and mice. An
      extremely G+C-rich region lacking canonical TATA and CAAT boxes was found
      upstream of the most 5' RACE sequence, suggesting that a housekeeping-like
      promoter drives the broad expression of Staufen in mammalian cells. This work
      represents the first step toward production of knockout mice and the elucidation
      of putative Staufen-linked hereditary diseases in humans.

PMID- 10882233
TI  - Collagen alpha1(I) gene contains an element responsive to tumor necrosis factor
      alpha located in the 5' untranslated region of its first exon.
AB  - The aims of the present study were to identify the cis-acting element through
      which tumor necrosis factor-alpha (TNFalpha) inhibits collagen alpha1(I) gene
      transcription and the trans-acting factors involved in this effect in cultured
      hepatic stellate cells. Deletion analysis of the collagen alpha1(I) promoter
      demonstrated that TNFalpha inhibited gene expression through an element located
      between -59 and + 116 bp relative to the transcription start site. DNase I
      protection assays revealed a footprint between +68 and +86 bp of the collagen
      first exon, the intensity of which decreased when the DNA probe was incubated
      with nuclear protein from TNFalpha-treated hepatic stellate cells. This footprint
      contained a G+C-rich box. Transfection experiments demonstrated that mutations in
      this G+C-rich element abrogated the inhibitory effect of TNFalpha on the collagen
      alpha1(I) promoter. Gel retardation experiments using a radiolabeled
      oligonucleotide containing sequences of this region confirmed that TNFalpha
      treatment decreased the formation of two complexes between nuclear proteins and
      DNA. These complexes were efficiently blocked with an oligonucleotide containing
      an Spl-binding site and were supershifted with specific Spl and Sp3 antibodies.
      These results suggest that TNFalpha inhibits collagen alpha1(I) gene expression
      by decreasing the binding of Spl to a G+C-rich box in the 5' untranslated region
      of its first exon.

PMID- 10882234
TI  - N-Myc shares cellular functions wiht c-Myc.
AB  - N-Myc is a member of the myc family of proto-oncogenes involved in initiation and
      progression of tumors. While c-MYC, the most characterized member of the family,
      is well known for its role in cellular proliferation and apoptosis, the function
      of N-MYC in differentiation and proliferation remains unclear. N-Myc mutant mice
      present a phenotype more consistent with a role of N-MYC protein in proliferation
      of precursor populations than in differentiation per se. Recent studies have also
      shown that N-MYC can enhance apoptosis and shorten the G1 phase of the cell
      cycle. However, the role of N-MYC in instigating cell-cycle progression has not
      been clearly demonstrated. Here, we demonstrate that overexpression of N-myc or
      activation of inducible N-MYC proteins is sufficient to induce apoptosis in serum
      starved fibroblast cells, an effect that can be counteracted by overexpression of
      Bcl-2. Moreover, N-MYC can induce the reentry of quiescent cells into the cell
      cycle even in the absence of external stimuli. These results indicate that N-MYC
      and c-MYC share many properties, supporting the model that MYC-specific roles
      during embryonic development are mediated, at least in part, via their specific
      profile of expression rather than by their different protein functions.

PMID- 10882235
TI  - Alternative splicing of Xenopus alphafast-tropomyosin pre-mRNA during
      development: identification of determining sequences.
AB  - The Xenopus alphafast-tropomyosin gene contains in its central part a set of
      mutually exclusive exons, designated 6A and 6B, which are incorporated into mRNA
      encoding, respectively, nonmuscle and muscle tropomyosins. In this study, we show
      that usage of both exons is strictly regulated during development, exon 6A being
      used in the oocyte and nonmuscle tissues of the embryo, while exon 6B is used in
      muscle tissues. An approach of transient embryo transgenesis was developed to
      study the mechanisms involved in the splice site choice during development. We
      demonstrate that a-tropomyosin minigenes driven by tissue-specific promoters that
      target gene expression in nonmuscle and muscle tissues recapitulate the splicing
      pattern of the endogenous gene. A mutational analysis showed that regulation
      occurred at both exons 6A and 6B in muscle and nonmuscle tissues. In this
      context, we have identified an element located in the intron downstream of 6A
      that participates in the recognition of the weak 5' splice site of exon 6A and
      the repression of exon 6B in nonmuscle cells.

PMID- 10882236
TI  - The gene encoding the 17-kDa antigen of Bartonella henselae is located within a
      cluster of genes homologous to the virB virulence operon.
AB  - A Bartonella henselae genomic A library was screened with antiserum generated in
      mice against live B. henselae. One of the immunoreactive clones expressed a 17
      kDa antigen that was characterized previously as an immunodominant protein of B.
      henselae. Sequence analysis of the recombinant clone, pBHIM-2, revealed that the
      open reading frame (ORF) encoding the 17-kDa antigen was situated between
      homologs of virB4 and virB6, two genes that belong to the virB operon. The virB
      operon has been associated with the transfer of oncogenic T-DNA in Agrobacterium
      tumefaciens and with secretion of the pertussis toxin in Bordetella pertussis.
      Downstream of the virB6 gene within pBHIM-2 was a partial open reading frame that
      was homologous to the virB8 gene. Rescreening of the library by plaque
      hybridization using probes specific to the 5' and 3' ends of the pBHIM-2 insert
      resulted in the isolation of recombinant clones containing additional virB genes.
      Assembly of the sequences obtained from the recombinant clones revealed that
      eight of the open reading frames encode homologs of the VirB proteins. The
      homology and colinearity with the virB genes suggest that the gene encoding the
      17-kDa antigen is expressed within the virB locus of B. henselae.

PMID- 10882237
TI  - Diagnosis and management of acute ureterolithiasis: CT is truth.

PMID- 10882238
TI  - A balanced subspecialization strategy for radiology in the new millennium.

PMID- 10882239
TI  - The effect of imaging guidelines on the number and quality of outpatient
      radiographic examinations.
AB  - OBJECTIVE: A significant percentage of outpatient diagnostic radiology is
      performed by nonradiologists. Studies have shown nonradiologists have higher
      utilization and cost, as well as quality problems. We sought to determine if, in
      a managed care environment, a set of guidelines limiting imaging privileges of
      nonradiologist physicians could decrease imaging costs while ensuring that
      equipment and personnel providing imaging were of the highest quality. MATERIALS
      AND METHODS: We determined the number and type of radiographic imaging studies
      performed the year after these guidelines were set in place (1997) and compared
      these findings with those of the year before the guidelines were established
      (1995) and with preguideline trends. We established quality criteria and, based
      thereon, inspected imaging offices. RESULTS: The number of radiographic
      examinations per 1000 enrollees decreased 20-25% from the previous trend.
      Nonradiologists' share of the total fell from 39% to 15%. No deficiencies were
      found in the inspection of five radiologists' offices, whereas significant
      deficiencies of equipment, equipment maintenance, or documentation of the
      examinations performed were found in 78% of nonradiologists' offices. None of the
      quality indicators monitored by the health plan showed significant change.
      CONCLUSION: Specific guidelines can effect change in the location and number of
      radiologic examinations performed, with an improvement in the quality of the
      studies and a decrease in radiation dose and cost. No decline in quality of care
      appears to result, despite claims by opponents to such changes that widespread
      serious quality impairment would occur.

PMID- 10882240
TI  - Liability of interpreting too many radiographs.

PMID- 10882241
TI  - Multiple bilateral masses detected on screening mammography: assessment of need
      for recall imaging.
AB  - OBJECTIVE: When multiple bilateral partially circumscribed masses having a
      similar appearance are detected on screening mammography, some radiologists
      recommend recall examination to identify imaging features suggestive of
      malignancy that are not evident on standard screening views. This study assesses
      the need for such recall imaging. SUBJECTS AND METHODS: Cases of multiple masses
      were identified by reviewing the mammographic reports of 84,615 consecutive
      screening examinations. Each case of multiple masses was prospectively
      interpreted as benign, with recommendations for follow-up mammography in 1 year
      and for aspiration of any palpable masses if clinically indicated. Subsequently
      diagnosed cancers were identified through data linkage with our regional tumor
      registry and through our institution's computer-based outcomes tracking system.
      RESULTS: Among 84,615 consecutive screening examinations, we identified 1440
      (1.7%) cases of multiple masses. Among the multiple-masses cohort, two interval
      cancers were found. Both were early-stage (T1bN0M0; T1cN0M0) and low-grade
      (histologic grade 1) cancers. The interval cancer rate among the multiple-masses
      cohort was 0.14%, which is somewhat lower than the age-matched United States
      incident cancer rate of 0.24%. CONCLUSION: The frequency of cancer development
      and the stage at cancer diagnosis among nonrecalled cases of multiple masses are
      similar to those observed in the general screening mammography population.
      Therefore, recall imaging for women with multiple masses does not appear to be
      justified.

PMID- 10882242
TI  - Mammographic and sonographic appearances of nodular adenosis.
AB  - OBJECTIVE: We determined whether nodular adenosis of the breast possesses any
      pathognomonic features on imaging studies. CONCLUSION: The imaging features of
      nodular adenosis are often benign-appearing and can be indistinguishable from
      other ellipsoid, circumscribed, or hypodense masses. Occasionally, nodular
      adenosis may appear suggestive of malignancy. Pathologic evaluation by excisional
      or large core needle biopsy is necessary for diagnosis.

PMID- 10882243
TI  - Dynamic high-spatial-resolution MR imaging of suspicious breast lesions:
      diagnostic criteria and interobserver variability.
AB  - OBJECTIVE: Our study was undertaken to develop diagnostic rules and to assess the
      reproducibility of dynamic and morphologic parameters for the characterization of
      suspicious breast lesions using dynamic high-spatial-resolution MR imaging.
      MATERIALS AND METHODS: Fifty-seven patients with suspicious mammographic or
      palpable findings underwent preoperative contrast-enhanced MR imaging of the
      breast using a three-time-point method of acquisition. Each lesion was
      prospectively analyzed by two independent radiologists for morphologic and visual
      dynamic enhancement characteristics. A classification and regression tree was
      used to examine the optimal order, cutoff points, and combination of imaging
      parameters to build a diagnostic rule separating benign from malignant lesions
      using histopathology findings as the standard of reference. Kappa statistics were
      used to determine observer variability. RESULTS: Among 23 benign and 34 malignant
      lesions (12 invasive, three ductal carcinoma in situ, and 19 mixed cancer),
      margin morphology (p = 0.001) and enhancement pattern (p = 0.001) were the most
      significant MR imaging findings for lesion characterization. Focal mass lesions
      were classified as malignant when spiculated margins or both the washout
      enhancement pattern and "nonsmooth" margins were present. Interobserver agreement
      was almost perfect for washout pattern and substantial for margin assessment. In
      the limited population tested retrospectively, the diagnostic rule yielded a
      sensitivity and positive predictive value of 97% each and a specificity and
      negative predictive value of 96% each. CONCLUSION: The washout enhancement
      pattern combined with lesion margin assessment on dynamic contrast-enhanced high
      resolution MR imaging of the breast allows reproducible lesion characterization
      and may be a highly specific diagnostic tool.

PMID- 10882244
TI  - Comparing the performance of mammographic enhancement algorithms: a preference
      study.
AB  - OBJECTIVE: The objective of this study was to compare the performance of four
      image enhancement algorithms on secondarily digitized (i.e., digitized from film)
      mammograms containing masses and microcalcifications of known pathology in a
      clinical soft-copy display setting. MATERIALS AND METHODS: Four different image
      processing algorithms (adaptive unsharp masking, contrast-limited adaptive
      histogram equalization, adaptive neighborhood contrast enhancement, and wavelet
      based enhancement) were applied to one image of secondarily digitized mammograms
      of forty cases (10 each of benign and malignant masses and 10 each of benign and
      malignant microcalcifications). The four enhanced images and the one unenhanced
      image were displayed randomly across three high-resolution monitors. Four expert
      mammographers ranked the unenhanced and the four enhanced images from 1 (best) to
      5 (worst). RESULTS: For microcalcifications, the adaptive neighborhood contrast
      enhancement algorithm was the most preferred in 49% of the interpretations, the
      wavelet-based enhancement in 28%, and the unenhanced image in 13%. For masses,
      the unenhanced image was the most preferred in 58% of cases, followed by the
      unsharp masking algorithm (28%). CONCLUSION: Appropriate image enhancement
      improves the visibility of microcalcifications. Among the different algorithms,
      the adaptive neighborhood contrast enhancement algorithm was preferred most
      often. For masses, no significant improvement was observed with any of these
      image processing approaches compared with the unenhanced image. Different image
      processing approaches may need to be used, depending on the type of lesion. This
      study has implications for the practice of digital mammography.

PMID- 10882245
TI  - Cost-effectiveness of stereotactic 11-gauge directional vacuum-assisted breast
      biopsy.
AB  - OBJECTIVE: The purpose of our study was to determine the frequency with which
      stereotactic 11-gauge directional vacuum-assisted breast biopsy obviated a
      surgical procedure and to calculate cost savings attributable to that biopsy
      method. MATERIALS AND METHODS: We retrospectively reviewed 200 consecutive
      solitary nonpalpable lesions on which stereotactic 11-gauge directional vacuum
      assisted breast biopsy was performed. Cost savings were calculated using Medicare
      reimbursements. Mammograms, histologic findings, and medical records were
      reviewed. RESULTS: Stereotactic 11-gauge directional vacuum-assisted biopsy
      obviated a surgical procedure in 151 (76%) of 200 lesions, including 112 (73%) of
      154 calcific lesions and 39 (85%) of 46 masses. Reasons for not obviating a
      surgical procedure in 49 lesions (25%) included recommendation for surgical
      biopsy in 35 lesions (18%), small carcinomas treated by excision in 10 lesions
      (5%), and histologic underestimation in four lesions (2%). Stereotactic 11-gauge
      directional vacuum-assisted biopsy decreased the cost of diagnosis by S264 per
      case, a 20% ($264/$1289) decrease in the cost of diagnosis compared with surgical
      biopsy. Of 200 lesions that had stereotactic 11-gauge directional vacuum-assisted
      biopsy, 106 (53%) would not have been amenable to 14-gauge automated core biopsy
      because of their small size, their superficial location, or inadequate breast
      thickness. CONCLUSION: Stereotactic 11-gauge directional vacuum-assisted breast
      biopsy obviated a surgical procedure in 76% of lesions, yielding a 20% decrease
      in cost of diagnosis compared with surgical biopsy. Although savings per case are
      modest, 11-gauge directional vacuum-assisted biopsy expands the spectrum of
      lesions amenable to stereotactic biopsy, increasing cost savings in the
      population.

PMID- 10882246
TI  - Stereotactic breast biopsy: recumbent biopsy using add-on upright equipment.
AB  - OBJECTIVE: The purpose of the study was to show that stereotactic breast biopsy
      can be performed effectively and accurately using add-on stereotactic equipment
      when it is performed with the patient in a decubitus or recumbent position.
      MATERIALS AND METHODS: We retrospectively reviewed the results of 225
      stereotactic core breast biopsies performed during a 42-month period. The
      biopsies were performed using a reclining mammography chair and add-on
      stereotactic equipment. Procedures were performed with the patient in the right
      or left lateral decubitus position or upright. Patients with benign biopsy
      results were followed up mammographically at 6 months initially, then yearly.
      RESULTS: Of the 225 lesions biopsied stereotactically, 205 lesions (91%) were
      biopsied with the patient in the decubitus (right or left) position and 20 (9%)
      biopsied with the patient upright. Pathology results were classified as abnormal
      in 45 lesions (20%) and normal in 180 lesions (80%). All but one of the abnormal
      lesions were followed up with surgical excision. One hundred thirty-four of the
      180 benign lesions have been followed up with at least one 6-month mammogram
      (follow-up range, 6-40 months), and none of the lesions has been subsequently
      proven malignant. CONCLUSION: Stereotactic core biopsy can be performed
      effectively and accurately using standard add-on equipment when it is performed
      with the patient in the decubitus position. This approach obviates the use of
      dedicated prone stereotactic equipment.

PMID- 10882247
TI  - In situ and infiltrating ductal carcinoma arising in a breast hamartoma.

PMID- 10882248
TI  - Outcome of pregnancies with rapid embryonic heart rates in the early first
      trimester.
AB  - OBJECTIVE: We conducted a study to determine the upper limits of normal embryonic
      heart rate at or before 7.0 weeks' gestational age and to assess outcome of
      pregnancies in which the early embryonic heart rate is rapid. SUBJECTS AND
      METHODS: We recorded embryonic heart rates in 2817 sonograms at or before 7.0
      weeks' gestation performed between January 1993 and June 1998. The upper limit of
      normal heart rate in two gestational age ranges (before 6.3 weeks and 6.3-7.0
      weeks) was computed as the average of two values: mean heart rate + 1.96 standard
      deviations and the rate above which 2.5% of embryos in our population were
      measured. Pregnancy outcome in cases with rapid embryonic heart rates was
      compared with pregnancy outcome in a control group with normal rates. RESULTS:
      The upper limit of normal heart rate was 134 beats per minute before 6.3 weeks'
      gestation and 154 beats per minute at 6.3-7.0 weeks' gestation. Forty-one embryos
      had rapid early heart rates and known first-trimester outcome, of which 37
      (90.2%) were alive at the end of the first trimester. Pregnancy outcome was
      available in 33 of the 37 first-trimester survivors (four were lost to follow-up
      before delivery), and 30 of these 33 (90.9%) were healthy neonates. These short-
      and long-term outcomes were not significantly different from those of the control
      group of embryos with normal early heart rates (p > 0.20, Fisher's exact test).
      CONCLUSION: A rapid early embryonic heart rate is one that is at least 135 beats
      per minute before 6.3 weeks or at least 155 beats per minute at 6.3-7.0 weeks.
      Pregnancies in which the embryo has a rapid early heart rate have a good
      prognosis, with a high likelihood of normal outcome.

PMID- 10882249
TI  - Radiologists' confidence in interpretation of sonography and CT in suspected
      pediatric appendicitis.
AB  - OBJECTIVE: We sought to determine radiologists' confidence in interpretation of
      sonography and CT performed using rectal contrast material for diagnosing
      pediatric appendicitis. SUBJECTS AND METHODS: We prospectively examined 139
      children and young adults with equivocal clinical findings for appendicitis who
      were seen in the emergency department of an urban pediatric teaching hospital
      between July and December, 1998. Patients were initially examined with pelvic
      sonography. If the sonographic results were equivocal or if the appendix was not
      visualized, CT was performed. Radiologists recorded their level of confidence in
      interpretation of the sonograms and CT examinations. RESULTS: Sonography was
      interpreted with very low, low, or medium confidence in 59 (42.4%) of 139
      patients and with high or very high confidence in 80 (57.6%) of 139. CT was
      interpreted with very low, low, or medium confidence in nine (8.3%) of 108 and
      with high or very high confidence in 99 (91.7%) of 108 children. Radiologists
      were more confident in their interpretation of CT than sonography (p < 0.001). If
      the sonography was a true-positive examination, radiologists were more confident
      in its interpretation than if it was a false-positive study (p = 0.003).
      Radiologists were more confident in sonographic interpretation of a true-negative
      examination than of a false-negative study (p = 0.03). Patient age and sex and
      the radiologists' level of experience did not make a significant difference in
      the confidence of interpretation of sonography or CT. CONCLUSION: In the
      evaluation of childhood appendicitis, radiologists' confidence in interpretation
      is influenced by the choice of imaging technique as well as by the results of the
      study.

PMID- 10882250
TI  - Development and duration of radiographic signs of bone healing in children.
AB  - OBJECTIVE: Few articles report the evaluation of pediatric fracture healing and
      dating based on radiographic appearance. We established a timetable for expected
      radiographic changes visible during bone healing in otherwise healthy children.
      MATERIALS AND METHODS: We examined 707 radiographs of fractured forearms in 141
      patients. Each fracture was assessed by a pediatric radiologist who was unaware
      of the timing of the initial injury. Assessment included the following features:
      fracture margins, fracture gap, periosteal reaction, callus, bridging, and
      remodeling. The time interval between injury and the appearance of the
      radiographic features and the duration of radiographic signs were determined and
      correlated with age, sex, angulation, displacement, and location. RESULTS:
      Sclerosis at the fracture margins was evident in 85% of fractures 5 weeks after
      injury. Widening of the fracture gap was observed in 62% of fractures at 6 weeks.
      Periosteal reaction was evident on all images by 4 weeks, and after 7 weeks,
      periosteal reaction was separable from cortex in only 10% of fractures. Fracture
      callus had a density equal to or greater than that of adjacent cortex 10 weeks
      after injury in 90% of fractures. CONCLUSION: A wide variation exists in the
      appearance and duration of the radiographic signs of bone healing. Marginal
      sclerosis should be an expected radiographic sign of normal bone healing.
      Applying maximum and minimum time spans to objective radiographic signs may aid
      in fracture dating.

PMID- 10882251
TI  - Inflammatory bowel disease in children and young adults: correlation of
      sonographic and clinical parameters during treatment.
AB  - OBJECTIVE: The objective of this study was to evaluate the sonographic findings
      of inflammatory bowel disease activity in children undergoing treatment. SUBJECTS
      AND METHODS: Eighty-eight sonograms were obtained of 23 bowel segments in 17
      children and young adults (age range, 10-21 years; mean, 16 years) with new or
      recurrent inflammatory bowel disease. Sixteen segments were involved with Crohn's
      disease and seven with ulcerative colitis. Serial sonography (range, two to eight
      examinations; mean, four per segment) was performed while patients underwent
      treatment. Bowel wall thickness measurements and color and power Doppler
      sonography grading were recorded and compared with clinical data. RESULTS: All 17
      patients had at least one abnormal bowel segment on initial sonography. The
      correlation was significant (p < 0.01). Agreement was 91% on direction of change
      over time between bowel wall thickness and Doppler grades, with 100% correlation
      between color and power Doppler sonography grades. In patients with Crohn's
      disease, the correlation was significant (p < 0.05) between bowel wall thickness
      and Doppler grades with two of seven and four of seven clinical parameters,
      respectively. In patients with ulcerative colitis, the correlation was
      significant (p < 0.05) between bowel wall thickness and Doppler sonography grades
      with four of seven and three of seven clinical parameters, respectively. The
      erythrocyte sedimentation rate correlated with all sonographic measurements in
      both patient groups. Combining bowel wall thickness and Doppler sonography, the
      percentage of agreement was significant in the direction of change, with five of
      seven clinical parameters in both patient groups. CONCLUSION: Gray-scale and
      color or power Doppler sonography can show changes in disease activity in
      children and young adults undergoing treatment for inflammatory bowel disease.

PMID- 10882252
TI  - Doppler waveform of hepatic veins in healthy children.
AB  - OBJECTIVE: This study intends to document the presence or absence of triphasic
      waveforms in hepatic veins in healthy children. Does absence of triphasic hepatic
      vein flow indicate hepatic abnormality? SUBJECTS AND METHODS: One hundred
      children without a known hepatic or intrathoracic abnormality underwent Doppler
      sonography of their hepatic veins. Fifty girls and 50 boys were divided into five
      age groups. RESULTS: Forty-two children had triphasic flow in all three hepatic
      veins. Veins approaching an angle of 90 degrees with the inferior vena cava could
      not be assessed or had the least flow modulations despite angle correction.
      Neonates had the highest percentage of monophasic flow (seven of 21) in all three
      hepatic veins and none had triphasic flow in all three veins. CONCLUSION: Not all
      healthy children have a triphasic flow pattern in all hepatic veins. Before
      suspecting hepatic abnormality with abnormal parenchymal compliance (cirrhosis,
      graft rejection) by virtue of lack of triphasic hepatic vein flow, a normal
      variant of the flow should be considered. Only the change of a previously
      documented triphasic flow to monophasic flow in a given vein should be assessed
      as a sign of possible abnormality.

PMID- 10882253
TI  - Selective intraarterial contrast-enhanced CT of pancreaticoduodenal tumors: early
      clinical experience in evaluating blood supply and detectability.
AB  - OBJECTIVE: The purpose of this study was to compare CT with selective
      intraarterial contrast enhancement with IV contrast-enhanced CT for diagnostic
      usefulness in the detection of tumors in the pancreaticoduodenal region. SUBJECTS
      AND METHODS: intraarterial contrast enhanced CT was performed in 36 patients with
      tumors of the pancreaticoduodenal region. Feeding arteries of the tumors and
      distribution of hyperattenuating areas on intraarterial contrast-enhanced CT were
      analyzed with various routes of contrast material injections. The intraarterial
      contrast-enhanced CT scans were compared with the IV contrast-enhanced CT scans.
      RESULTS: In all 29 patients with standard vascular anatomy, the right cephalic
      portion of the pancreatic head was enhanced on CT during common hepatic or
      gastroduodenal arteriography and the left caudal portion was enhanced on CT
      during superior mesenteric arteriography. The enhanced areas were complementary
      to each other in the whole pancreatic head, including the tumor. Tumor
      conspicuity from the surrounding pancreatic tissue on intraarterial contrast
      enhanced CT was not superior to that on IV contrast-enhanced CT in all but four
      patients with cystic tumors. After intraarterial contrast-enhanced CT, three
      patients with tumors less invasive than pancreatic ductal carcinoma underwent
      local resection of their lesions. CONCLUSION: Intraarterial contrast-enhanced CT
      for pancreaticoduodenal tumors has potential technical problems and is not
      valuable in improving the detectability of tumors other than cystic lesions
      because the enhancement of the wall and septa of the tumor is emphasized.
      However, the feeding artery of the tumor and its surrounding tissue were clearly
      depicted.

PMID- 10882254
TI  - Centennial photo page. From the AJR archives: celebrating the ARRS centennial.
      The use of silicone foam for examining the human sigmoid colon.

PMID- 10882255
TI  - CT of primary cystic pancreatic neoplasms: can CT be used for patient triage and
      treatment?
AB  - OBJECTIVE: The purpose of this study was to determine whether CT can be used to
      distinguish serous cystadenomas from mucinous cystadenomas or cystadenocarcinomas
      of the pancreas and play an enhanced role in patient triage and treatment.
      MATERIALS AND METHODS: A blinded retrospective analysis of CT scans from 50
      patients with pathologically proven primary cystic pancreatic neoplasms was
      performed independently by three radiologists. Using classic CT criteria as
      reported in the literature, each tumor was categorized as definitely serous,
      mucinous, or indeterminate. Tumor location, size, presence of calcification, and
      size of largest cyst were recorded. Data for each reviewer were analyzed
      independently. Consensus data were then subjected to multivariate logistic
      regression analysis. RESULTS: The ability of our reviewers to diagnose serous
      neoplasms ranged from 23% to 41%. Eight mucinous neoplasms were mistaken for
      serous tumors by two of the three reviewers. When consensus between at least two
      of the three reviewers was used for diagnosis, 27% of serous neoplasms were
      correctly diagnosed and all of the mucinous tumors were correctly identified as
      uncertain or mucinous, yielding the same clinical end point. For multivariate
      logistic regression analysis, a cyst smaller than 2 cm had a statistically
      significant association (p = 0.005) with serous tumors, and the presence of
      peripheral tumoral calcification had a statistically significant association (p =
      0.01) with mucinous tumors. CONCLUSION: There is significant variability in the
      CT appearance of serous and mucinous neoplasms of the pancreas, making CT an
      insensitive tool for differentiating these tumors. All tumors with peripheral
      calcifications were identified as mucinous neoplasms.

PMID- 10882256
TI  - Alterations in hepatic perfusion resulting from splanchnic venous luminal
      compromise caused by pancreatic carcinoma.
AB  - OBJECTIVE: We determined whether alterations in hepatic enhancement exist on dual
      phase helical CT of the liver in patients with splanchnic venous luminal
      compromise resulting from pancreatic adenocarcinoma. SUBJECTS AND METHODS: We
      examined the extent of hepatic enhancement on dual phase helical CT in 22
      patients with pancreatic adenocarcinoma. Eleven patients had splanchnic venous
      luminal narrowing (flattening along at least 120 degrees of the circumference) of
      the superior mesenteric vein with (n = 3) or without (n = 8) portal vein
      involvement caused by tumor. In the remaining patients, splanchnic vasculature
      appeared normal. An additional 16 patients without pancreatic or hepatic
      abnormality who underwent dual phase helical CT served as control subjects. We
      compared the extent of arterial phase and portal venous phase enhancement among
      the three groups. RESULTS: The group of patients with splanchnic venous luminal
      compromise had significantly higher hepatic enhancement during the arterial phase
      (p < 0.01) and lower enhancement during the portal venous phase (p < 0.05)
      compared with the other two groups of patients. No significant difference in
      hepatic enhancement during either phase was noted between the control subjects
      and the patients with normal vasculature. CONCLUSION: Because hepatic enhancement
      correlates with perfusion, splanchnic venous luminal compromise resulting from
      pancreatic adenocarcinoma likely causes decreased portal venous flow and
      compensatory increased hepatic arterial flow. This finding supports other
      evidence of a homeostatic mechanism that maintains hepatic perfusion.

PMID- 10882257
TI  - Helical CT protocols for the abdomen and pelvis: a survey.
AB  - OBJECTIVE: We surveyed members of the Society of Computed Body
      Tomography/Magnetic Resonance to evaluate current techniques used for helical CT
      in the abdomen and pelvis. MATERIALS AND METHODS: The survey was distributed to
      70 members (36 institutions) of the Society of Computed Body Tomography/Magnetic
      Resonance. The survey included general questions related to abdominal and pelvic
      helical CT and also asked the members to write a protocol for 12 hypothetical
      requisitions. RESULTS: Thirty-two members (46%) responded, representing 28
      institutions (78%). The number of protocols for helical CT of the abdomen and
      pelvis at each institution ranges from 2 to 35 (median, 11). IV contrast material
      is administered for 90% (median) of abdominal and pelvic CT examinations.
      Nonionic contrast material is used for 68% (median) of these examinations. IV
      contrast material is used by 100% of institutions for tumor staging protocols
      except for one institution that does not use IV contrast material for lymphoma
      staging. Fifty percent of the institutions obtain two- or three-phases of liver
      images for breast cancer staging. For all protocols, the average collimation and
      reconstruction interval is 7 mm except for renal (5 mm) and adrenal (4 mm)
      protocols. Rectal contrast material is administered most commonly for colon
      cancer staging (39% of institutions). CONCLUSION: There is a wide range in the
      number of protocols used for helical CT in the abdomen and pelvis among the
      responding institutions. Most protocols include use of nonionic IV contrast
      material injected at a rate of 3 ml/sec and a collimation of 7 mm.

PMID- 10882258
TI  - CT features of Castleman disease of the abdomen and pelvis.
AB  - OBJECTIVE: The purpose of this study was to describe the CT features of Castleman
      disease in the abdomen and pelvis. CONCLUSION: The most frequent appearance of
      abdominal or pelvic Castleman disease is of a single, well-defined enhancing
      mass. Smaller tumors (<5 cm) display homogeneous contrast enhancement; larger
      tumors (>5 cm) show heterogeneous enhancement and attenuation when correlated
      with central necrosis and degeneration. Calcification was seen in 31% of the
      cases. Castleman disease may be considered in the differential diagnosis of a
      discrete enhancing mass in the abdomen or pelvis.

PMID- 10882259
TI  - Colonic stent placement facilitated by percutaneous cecostomy and antegrade
      enema.

PMID- 10882260
TI  - Tuberculous colitis: radiologic-colonoscopic correlation.

PMID- 10882261
TI  - CT and sonographically guided biopsy in a patient with intestinal mucormycosis.

PMID- 10882262
TI  - Appendiceal ganglioneuromas and pheochromocytoma in neurofibromatosis type 1.

PMID- 10882263
TI  - Silicon ring vertical gastroplasty for morbid obesity: spectrum of radiologic
      findings.

PMID- 10882264
TI  - Value of Doppler sonography in revealing transjugular intrahepatic portosystemic
      shunt malfunction: a 5-year experience in 216 patients.
AB  - OBJECTIVE: The purpose of the study was to evaluate the long-term clinical
      efficacy of Doppler sonography in revealing failure of transjugular intrahepatic
      portosystemic shunts (TIPS). SUBJECTS AND METHODS: During a 5-year period, 1192
      Doppler examinations were performed in 216 patients with TIPS. No regular follow
      up shunt venography was performed. Doppler examinations were retrospectively
      compared with the results of shunt revisions. Sonograms with negative findings
      were compared with the patients' clinical status so that the number of false
      negative sonographic findings leading to an episode of shunt failure (recurrence
      of gastrointestinal bleeding or ascites) could be ascertained. Sonographic
      parameters assessed included diameter, velocity, flow volume, and congestion
      index of the portal vein; and shunt velocities. RESULTS: Doppler sonography
      revealed shunt occlusion in 25 of 26 angiographically proven cases (sensitivity,
      96%). The combination of velocity criteria (peak intrashunt velocity > or =250
      cm/sec, maximum velocity in the portal third of the shunt < or =50 cm/sec, or
      maximum portal vein velocity less than or equal to two thirds of the baseline
      value) revealed shunt stenosis in 103 of 110 cases (sensitivity, 94%). Doppler
      sonography missed a significant shunt stenosis that led to an episode of
      gastrointestinal bleeding or ascites recurrence in only seven cases. The
      congestion index of the portal vein showed significant differences between patent
      and malfunctioning shunts (p < 0.001). CONCLUSION: Doppler sonography is an
      effective primary imaging method for long-term follow-up of patients with TIPS.

PMID- 10882265
TI  - Transjugular intrahepatic portosystemic shunts (TIPS): effects of respiratory
      state and patient position on the measurement of Doppler velocities.
AB  - OBJECTIVE: The purpose of this prospective study was to examine the effects of
      patient position and respiratory state on the measurements of Doppler velocities
      in transjugular intrahepatic portosystemic shunts. SUBJECTS AND METHODS: Thirty
      eight transjugular intrahepatic portosystemic shunts in 34 consecutive patients
      were studied using Doppler sonography. Peak velocities were measured in the mid
      shunt with the patient in three positions (supine, sitting upright, and left
      lateral decubitus) and two respiratory states (deep inspiration and quiet
      respiration). A mixed linear regression model was used to assess statistically
      significant differences among the six velocity measurements. RESULTS: Peak
      velocities in the mid stent averaged 22 cm/sec greater in quiet respiration than
      in deep inspiration, which was a significant difference (p < 0.00001).
      Differences in velocities in the three patient positions were not significant (p
      = 0.53). Using 90-190 cm/sec as the normal range, the peak velocity shifted from
      normal to abnormal levels by changing respiratory state in 17 (45%) of 38
      studies. Using 60 cm/sec as the lower normal limit, the peak velocity fell below
      the normal range with inspiration in 10 (26%) of 38 studies. In 12 (32%) of 38
      studies, a decline in peak velocity exceeding 50 cm/sec could be induced by
      inspiration. CONCLUSION: Peak systolic velocity in transjugular intrahepatic
      portosystemic shunts is substantially altered by the respiratory state of the
      patient at the time of the measurement, but not by the patient position.
      Respiratory state must be taken into account in the interpretation of peak
      velocity for shunt stenosis.

PMID- 10882266
TI  - Transhepatic portosystemic shunts: CT appearance and anatomic correlation.

PMID- 10882267
TI  - Characterization of focal hepatic lesions with ferumoxides-enhanced T2-weighted
      MR imaging.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether ferumoxides-enhanced
      MR imaging of focal hepatic lesions provides distinctive signal intensity and
      lesion-to-liver contrast changes for benign and malignant lesions, helping to
      further characterize and differentiate these lesions. MATERIALS AND METHODS: Data
      analysis was performed on 70 patients, with previously identified focal hepatic
      lesions, who underwent MR imaging of the liver before and after IV administration
      of ferumoxides (10 micromol Fe/kg). Lesions analyzed with pathologically proven
      diagnoses included metastases (n = 40), hepatocellular carcinoma (n = 11),
      cholangiocarcinoma (n = 6), hemangioma (n = 4), focal nodular hyperplasia (n =
      6), and hepatocellular adenoma (n = 3). Response variables measured and
      statistically compared included the percentage of signal-intensity change and
      lesion-to-liver contrast. RESULTS: Focal nodular hyperplasia showed significant
      signal intensity loss on ferumoxides-enhanced T2-weighted images (mean, -43%+/
      6.7%, p < 0.01). All other lesion groups showed no statistically significant
      change in signal intensity on ferumoxides-enhanced T2-weighted images, although
      signal intensity loss was seen in some individual hepatocellular adenomas (mean, 
      6.6%+/-24.0%) and hepatocellular carcinomas (mean, -3.3%+/-10.3%). All lesions,
      with the exception of hepatocellular carcinoma, had a marked increase in lesion
      to-liver contrast on ferumoxides-enhanced T2-weighted images, which was
      statistically significant for metastases and hemangioma (p < 0.02). CONCLUSION:
      Focal nodular hyperplasia shows significant decrease in signal intensity on
      ferumoxides-enhanced T2-weighted images, which may aid in the differentiation of
      focal nodular hyperplasia from other focal hepatic lesions. Other lesions,
      namely, hepatocellular adenoma and carcinoma, can have reticuloendothelial
      uptake, but usually to a lesser degree than that of focal nodular hyperplasia.

PMID- 10882268
TI  - Hepatic angiosarcoma: findings on multiphasic contrast-enhanced helical CT do not
      mimic hepatic hemangioma.
AB  - OBJECTIVE: The objective of our study was to identify multiphasic contrast
      enhanced helical CT findings of angiosarcoma of the liver to determine whether
      this tumor could be confused with hemangioma of the liver. CONCLUSION:
      Angiosarcoma of the liver is a multifocal tumor with a variety of findings on
      multiphasic contrast-enhanced helical CT. None of the findings would usually be
      confused with the typical findings of hepatic hemangioma.

PMID- 10882269
TI  - Value of dynamic MR imaging in assessing endometrial carcinoma involvement of the
      cervix.
AB  - OBJECTIVE: The purpose of this study was to evaluate endometrial carcinoma
      involvement of the cervix using dynamic MR imaging compared with T2-weighted and
      contrast-enhanced T1-weighted MR imaging. SUBJECTS AND METHODS: In 42 patients
      with endometrial carcinoma, T2-weighted MR imaging using rapid acquisition with
      relaxation enhancement, dynamic MR imaging using gradient-echo sequences, and
      contrast-enhanced T1-weighted MR imaging using spin-echo sequences were performed
      before treatment. We evaluated patterns of enhancement in the cervix and tumor.
      In 39 of the 42 patients who underwent surgical treatment, we compared MR imaging
      findings with histologic results concerning cervical involvement. RESULTS:
      Enhancement of the cervical epithelium was greater than that of the tumor and
      cervical stroma on dynamic MR imaging in most patients. In assessing cervical
      involvement, the accuracy of T2-weighted, dynamic, and contrast-enhanced T1
      weighted MR imaging was 85%, 95%, and 90%, respectively; no statistically
      significant difference was observed. False-positive cases on T2-weighted MR
      imaging were correctly identified as having no cervical involvement on dynamic MR
      imaging using the finding of continuous enhancement of the cervical epithelium.
      We found this finding to be reliable in assessing tumor involvement of the
      cervix. CONCLUSION: We believe that, in combination with T2-weighted MR imaging
      sequences, dynamic MR imaging is useful in assessing endometrial carcinoma
      involvement of the cervix.

PMID- 10882270
TI  - Seminal vesicle cyst with ipsilateral renal agenesis.
AB  - OBJECTIVE: The purpose of this study was to review the clinical symptoms and
      imaging features of a seminal vesicle cyst associated with renal agenesis.
      CONCLUSION: Patients with seminal vesicle cysts associated with renal agenesis
      may present with symptoms of bladder irritation or obstruction and with an
      abdominal or pelvic mass revealed on physical examination. Differentiation of a
      seminal vesicle cyst from other pelvic cystic masses may be determined with a
      spectrum of imaging techniques including excretory urography, sonography, CT, and
      MR imaging.

PMID- 10882271
TI  - Percutaneous reduction of ureterosciatic hernia.

PMID- 10882272
TI  - CT findings in posttransplantation lymphoproliferative disorder of renal
      transplants.

PMID- 10882273
TI  - Equilibrium-phase MR angiography of the aortoiliac and renal arteries using a
      blood pool contrast agent.
AB  - OBJECTIVE: The purpose of this study was to determine the diagnostic usefulness
      of a new blood pool contrast agent, NC100150, for assessing the aortoiliac and
      renal arteries. SUBJECTS AND METHODS: Twenty patients with hemodynamically
      significant stenosis (> or =50% of luminal diameter) of the iliac or renal
      arteries or an aortic aneurysm documented by digital subtraction angiography
      underwent MR angiography at 1.5 T after administration of NC100150. Three
      dimensional MR angiographic data sets were collected ill the equilibrium phase.
      In a prospective analysis, each vascular segment (16 segments per arterial tree)
      was evaluated. RESULTS: All patients tolerated the NC100150 administration well.
      Mean contrast-to-noise ratios of the vascular data collected in the equilibrium
      phase of NC100150 was 3.3+/-15.9. Compared with digital subtraction angiography,
      the sensitivity and specificity of MR angiography for the renal arteries were 82%
      and 98%, respectively; for the common iliac arteries, 86% and 97%, respectively;
      for the external iliac arteries, 80% and 100%, respectively; and for the internal
      iliac arteries, 71% and 977, respectively. All 83 aneurysmal changes revealed by
      digital subtraction angiograpy of the aortoiliac arteries were well displayed on
      the MR angiographic data sets. CONCLUSION: Equilibrium-phase NC 00150-enhanced
      three-dimensional MR angiography shows high specificity when evaluating the
      abdominal and pelvic vascular systems, but the attendant venous overlap can limit
      the assessment of stenosis in renal and pelvic arterial segments.

PMID- 10882274
TI  - Gadolinium-enhanced MR angiography: artifacts and pitfalls.

PMID- 10882275
TI  - MR perfusion imaging of the brain: techniques and applications.

PMID- 10882276
TI  - Physiologic variations in dural venous sinus flow on phase-contrast MR imaging.
AB  - OBJECTIVE: Our study quantifies normal physiologic variations of dural sinus flow
      using phase-contrast MR imaging. SUBJECTS AND METHODS: Fifteen volunteers were
      imaged using nontriggered and triggered phase-contrast MR venography of the
      superior sagittal and transverse sinuses. Triggered scans were obtained during
      regular breathing; nontriggered scans were obtained during regular breathing,
      breath-holding, deep inspiratory breath-holding, and deep expiratory breath
      holding. Analysis of variance, Bonferroni method, and Dunn post hoc analysis were
      used to determine any significant differences in the mean flow and velocity
      between the different breathing maneuvers. A paired t test was used to compare
      flow between sinuses during regular breathing. RESULTS: Deep inspiratory breath
      holding and deep expiratory breath-holding resulted in a significant decrease in
      blood flow and velocity in all dural sinuses compared with regular breathing.
      During deep inspiratory breath-holding, blood flow decreased 30.8% in the
      superior sagittal sinus, 19.7% in the left transverse sinus, and 19.1% in the
      right transverse sinus. Similarly, during deep expiratory breath-holding, blood
      flow decreased 30.2% in the superior sagittal sinus, 20.8% in the left transverse
      sinus, and 20.3% in the right transverse sinus. The sum of the flow in the
      transverse sinuses was significantly greater than in the sagittal sinus. Normal
      pulsatility of dural sinus blood velocity was also characterized for all measured
      sinuses. CONCLUSION: Characterization of variations in dural sinus velocity and
      flow as a function of the cardiac cycle and breathing maneuvers, using phase
      contrast MR imaging, may help separate physiologic from pathologic changes of
      flow resulting from conditions that influence the cerebrovascular circulation.

PMID- 10882277
TI  - Gadolinium mesoporphyrin as an MR imaging contrast agent in the evaluation of
      tumors: an experimental model of VX2 carcinoma in rabbits.
AB  - OBJECTIVE: We determined the enhancement features of experimentally induced
      malignant tumors on MR imaging with the use of gadolinium mesoporphyrin, a
      recently developed MR contrast agent that may be necrosis-specific. MATERIALS AND
      METHODS: VX2 carcinoma was inoculated into 24 rabbit thighs. T1-weighted contrast
      enhanced MR imaging with IV gadopentetate dimeglumine (2-min delay) and
      gadolinium mesoporphyrin (20-hr delay) was performed 3-4 days (n = 6), 6-7 days
      (n = 6), 10-11 days (n = 5), and 13-14 days (n = 7) after the implantation of VX2
      carcinoma. All tumors were sectioned along the same plane of MR images, and a
      detailed MR imaging-histopathologic correlation was performed. RESULTS:
      Pathologically, areas enhanced with gadolinium mesoporphyrin included necrotic
      tissue, viable tumor, inflammatory granulation tissue, hemorrhage, and fibrosis.
      On gadopentetate dimeglumine-enhanced MR images, unenhanced areas of the tumor
      corresponded with intratumoral necrosis and hemorrhage. CONCLUSION: Gadolinium
      mesoporphyrin enhances tumor necrosis on delayed phase MR imaging; however, it is
      impossible to specifically depict necrosis with gadolinium mesoporphyrin because
      it also enhances other parts of lesions, including viable tumor.

PMID- 10882278
TI  - The value of CT-guided percutaneous needle aspiration in immunocompromised
      patients with suspected pulmonary infection.
AB  - OBJECTIVE: We evaluated the diagnostic efficacy of CT-guided percutaneous needle
      aspiration in immunocompromised patients with suspected pulmonary infection.
      SUBJECTS AND METHODS: We reviewed the findings and yields of 24 CT-guided
      percutaneous needle aspirations in 21 immunocompromised patients. Cytologic
      evaluation and culture for aerobes, anaerobes, Mycobacterium species, and fungus
      were performed in all aspirates. RESULTS: We identified one or more etiologic
      microorganisms in 19 (79.2%) of 24 CT-guided percutaneous needle aspirations. Of
      19 aspirates with positive findings, single causal microorganisms were identified
      in 18. Staphylococcus aureus was found in four aspirates, and Aspergillus
      fumigatus in seven; these microorganisms were the principal bacterial (4/11) and
      fungal (7/9) causative organisms. One of the 19 aspirates with positive findings
      yielded two microorganisms. In the remaining five aspirates, no microorganisms
      were identified and cytologic examination revealed nonspecific inflammatory
      cells. No major complications were observed during or after the procedure.
      CONCLUSION: CT-guided percutaneous needle aspiration is a safe and useful
      diagnostic method for the identification of specific microorganisms in
      immunocompromised patients with suspected pulmonary infection.

PMID- 10882279
TI  - Diagnostic accuracy of CT-guided automated needle biopsy of lung nodules.
AB  - OBJECTIVE: The purpose of this study was to determine the factors influencing
      diagnostic accuracy in CT-guided automated needle biopsies of lung nodules.
      SUBJECTS AND METHODS: One hundred thirty-eight consecutive CT-guided automated
      needle biopsy procedures were performed in 123 patients (124 pulmonary nodules).
      Factors for diagnostic accuracy were evaluated through analysis of the
      procedures, which were classified into a success group (true-positive and true
      negative) and a failure group (false-positive and false-negative). RESULTS: Final
      diagnoses were 81 malignant lesions (91 biopsies) and 43 benign lesions (47
      biopsies). More than two CT-guided biopsies were performed for 13 lesions.
      Seventy lesions were true-positive, 44 were true-negative, three were false
      positive, and 21 were false-negative. The overall diagnostic accuracy was 82.6%.
      The sensitivity for malignancy and specificity for benign lesions were 76.9% and
      93.6%, respectively. Positive and negative predictive values were 95.9% and
      67.7%, respectively. Lesion size was a significant factor contributing to
      diagnostic accuracy (p = 0.014). Mean diameters of lesions (+/-SD) in the success
      and failure groups were 24.1+/-12.4 mm and 17.6+/-7.8 mm, respectively. For
      lesions 6-10 mm in diameter, diagnostic accuracy was 66.7%; for lesions 11-20 mm
      in diameter, 78.9%; for lesions 21-30 mm in diameter, 86.7%; for lesions 31-50 mm
      in diameter, 93.3%; and for lesions 51-70 mm in diameter, 100%. CONCLUSION:
      Lesion size was a determining factor in diagnostic accuracy. Diagnostic accuracy
      decreased in proportion to the decrease in the lesion diameter.

PMID- 10882280
TI  - Elastrofibroma dorsi of the chest wall.

PMID- 10882281
TI  - FDG PET of pleural effusions in patients with non-small cell lung cancer.
AB  - OBJECTIVE: We determined the ability of 18F-fluorodeoxyglucose (FDG) positron
      emission tomography (PET) to differentiate benign and malignant pleural effusions
      in patients with non-small cell lung cancer. MATERIALS AND METHODS: Over a 6-year
      period, we reviewed all patients with primary non-small cell lung cancer and a
      pleural effusion on staging CT who underwent FDG PET. We examined 25 patients (18
      men and seven women; age range, 37-86 years; mean age, 65 years). FDG PET
      revealed positive findings if pleural activity was greater than background
      mediastinal activity; FDG PET revealed negative findings if pleural activity was
      the same as or less than background mediastinal activity. Results of FDG PET were
      correlated with pathologic diagnosis determined with thoracentesis or pleural
      biopsy. RESULTS: All patients had effusions on the same side as the primary
      tumor. Twenty-two patients had a malignant pleural effusion confirmed with
      thoracentesis (n = 19) or biopsy (n = 3). FDG PET revealed positive findings in
      21 patients and negative findings in one. Three patients had no evidence of
      malignancy in the pleural space determined with cytologic findings (n = 2) or
      biopsy results (n = 1). FDG PET uptake revealed positive findings in one of these
      patients and negative findings in two. Therefore, of 22 patients with positive
      findings on FDG PET, 21 had pleural metastases, and of three patients with
      negative findings on FDG PET, one had metastases. The sensitivity, specificity,
      positive predictive value, negative predictive value, and accuracy of FDG PET for
      detecting pleural metastases were 95%, 67%, 95%, 67%, and 92%, respectively.
      CONCLUSION: This study suggests that FDG PET may be useful in improving staging
      evaluation in patients with non-small cell lung cancer and a pleural effusion.
      Increased pleural FDG uptake usually indicates pleural metastases; however,
      because the number of benign effusions studied was small, the relevance of
      negative findings on FDG PET in this setting is uncertain.

PMID- 10882282
TI  - Hemopericardium: an emergent finding in a case of blunt cardiac injury.

PMID- 10882283
TI  - MR imaging of overuse injuries of the Achilles tendon.
AB  - OBJECTIVE: This study was conducted to illustrate and classify the abnormalities
      found on high-resolution MR imaging of symptomatic Achilles tendons in athletic
      adult patients. SUBJECTS AND METHODS: One hundred patients with 118 painful
      Achilles tendons were imaged with a 1.5-T magnet. The tendon, peritendinous
      tissues, tendon insertion, and musculotendinous junction were examined on MR
      imaging. Twenty-eight patients underwent surgery, and histopathologic samples
      were taken in 13. Long-term follow-up was performed, on average, 3.4 years after
      MR imaging. RESULTS: Of 118 painful Achilles tendons, abnormalities were detected
      in 111. These were in the tendon (n = 90), surrounding structures, or both. Fifty
      four tendons had a focal area of increased intratendinous signal, best detected
      on axial high-resolution T1-weighted gradient-echo MR imaging. Histopathology
      confirmed abnormal tendon structure. Of the 21 surgically proven foci of
      tendinosis, 20 were revealed on MR imaging. At the level of the insertion,
      changes were found in the tendon in 15%, in the retrocalcaneal bursa in 19%, and
      in the calcaneal bone marrow in 8% of the studies. Abnormalities in peritendinous
      soft tissues were detected in 67%. More than one type of abnormality was found in
      64% of the studies. CONCLUSION: Lesions in the Achilles tendon and in the
      peritendinous structures can have similar clinical presentation. MR imaging
      detects and characterizes these changes. A more specific diagnosis and prognosis
      can be made with the use of MR imaging than with clinical examination alone.

PMID- 10882284
TI  - The "mini brain": plasmacytoma in a vertebral body on MR imaging.
AB  - OBJECTIVE: Patients with solitary plasmacytoma in the spine frequently require a
      biopsy for diagnosis of their condition. We report an appearance of plasmacytoma
      in the spine, which is sufficiently pathognomonic to obviate biopsy. CONCLUSION:
      Identification of a "mini brain" in an expansile lesion in the spine is
      characteristic of plasmacytoma. It is important that radiologists note this
      characteristic because biopsy can be avoided in patients with this appearance.
      Although biopsy might still be required at many institutions, at our institution,
      surgeons find this appearance sufficiently pathognomonic to bypass biopsy and
      start treatment.

PMID- 10882285
TI  - Interventional MR imaging for injection of sacroiliac joints in patients with
      sacroiliitis.

PMID- 10882286
TI  - The significance of a positive round belly sign on CT.

PMID- 10882287
TI  - Percutaneous biliary drainage in patients with nondilated bile ducts: use of a
      transjejunal approach.

PMID- 10882288
TI  - "Osteoporosis," "osteomalacia," and "osteopenia": proper terminology in
      childhood.

PMID- 10882289
TI  - Suspected brucellosis case prompts investigation of possible bioterrorism-related
      activity--New Hampshire and Massachusetts, 1999.
AB  - Brucella species, particularly B. melitensis and B. suis, are potential agents of
      biological terrorism (1,2). This report describes the public health and law
      enforcement assessment of a suspected case of brucellosis in a woman, in which
      the atypical clinical presentation and suspicious circumstances surrounding the
      case raised the possibility of biological terrorism. Although the investigation
      did not identify evidence of biological terrorism, the safe resolution of the
      case illustrates the value of integrated clinical, public health, and law
      enforcement biological terrorism preparedness and response.

PMID- 10882290
TI  - Adoption of protective behaviors among persons with recent HIV infection and
      diagnosis--Alabama, New Jersey, and Tennessee, 1997-1998.
AB  - A comprehensive human immunodeficiency virus (HIV) prevention strategy includes
      knowledge of HIV status, counseling to reduce high-risk behavior, and referral
      for appropriate care (1). After diagnosis, a substantial percentage of HIV
      infected persons reduce their high-risk sexual behaviors (2-4). This report
      presents data characterizing the sexual practices of persons with newly diagnosed
      HIV infection who have evidence of recently acquired infection. Characterizing
      these persons may assist in the development of risk-reduction efforts for HIV
      infected populations to prevent further HIV transmission.

PMID- 10882291
TI  - Occupational fatalities associated with 2,4-dichlorophenol (2,4-DCP) exposure,
      1980-1998.
AB  - 2,4-Dichlorophenol (2,4-DCP) is a feedstock chemical primarily used to produce
      the herbicide 2,4-dichloropheoxyacetic acid (2,4-D). In October 1998, the U.S.
      Environmental Protection Agency (EPA) was notified of the death of a worker
      acutely exposed to 2,4-DCP. Follow-up investigation by EPA, the Occupational
      Safety and Health Administration (OSHA), and CDC's National Institute for
      Occupational Safety and Health (NIOSH) identified four earlier deaths associated
      with acute 2,4-DCP exposure, which occurred during 1980-1992. All of these
      incidents resulted in rapid death after dermal exposure to the heated liquid form
      of the chemical. This report describes the five deaths associated with 2,4-DCP
      exposure (presented in the order in which they were identified) and provides
      recommendations for preventing additional deaths.

PMID- 10882292
TI  - Prevalence of selected cardiovascular disease risk factors among American Indians
      and Alaska Natives--United States, 1997.
AB  - Heart disease and stroke, the principal causes of cardiovascular disease (CVD),
      are the first and fifth leading causes of death among American Indians and Alaska
      Natives (AI/AN) (1,2). Risk factors for CVD frequently cluster, which may
      increase CVD risk multiplicatively (3). To characterize the prevalence of risk
      factors for CVD (i.e., hypertension, current cigarette smoking, high cholesterol,
      obesity, and diabetes) among AI/AN, CDC analyzed data from the 1997 Behavioral
      Risk Factor Surveillance System (BRFSS). This report summarizes the results of
      that analysis, which indicated that 63.7% of AI/AN men and 61.4% of AI/AN women
      who participated in the survey had one or more CVD risk factors.

PMID- 10882293
TI  - HIV/AIDS among men who have sex with men and inject drugs--United States, 1985
      1998.
AB  - Men who have sex with men and inject drugs (MSM/IDU) pose unique challenges for
      human immunodeficiency virus (HIV) risk reduction efforts because they have
      multiple risks for HIV acquisition and transmission. This report presents 1) the
      demographic characteristics of MSM/IDU diagnosed with acquired immunodeficiency
      syndrome (AIDS) in 1998 and MSM/IDU living with AIDS as of December 31, 1998; 2)
      trends in AIDS incidence among MSM/IDU from 1985 to 1998; and 3) information on
      selected behaviors from interviews of MSM/IDU who had AIDS diagnosed from 1996 to
      1998 in 12 states. The findings indicate that 1) over half of MSM/IDU with AIDS
      were non-Hispanic blacks and Hispanics, and most MSM/IDU with AIDS were reported
      from large metropolitan statistical areas (MSAs); 2) AIDS incidence has declined
      since 1996; and 3) a high prevalence of drug-related and sexual risk behaviors
      occurred among MSM/IDU with AIDS.

PMID- 10882294
TI  - Heat-related illnesses, deaths, and risk factors--Cincinnati and Dayton, Ohio,
      1999, and United States, 1979-1997.
AB  - During the summer of 1999, a heat wave occurred in the midwestern and eastern
      United States. This period of hot and humid weather persisted from July 12
      through August 1, 1999, and caused or contributed to 22 deaths among persons
      residing in Cincinnati (18 deaths) and Dayton (four deaths). A CDC survey of 24
      U.S. metropolitan areas indicated that Ohio recorded some of the highest rates
      for heat-related deaths during the 1999 heat wave, with Cincinnati reporting 21
      per million and Dayton reporting seven per million (CDC, unpublished data, 1999).
      This report describes four heat-related deaths representative of those that
      occurred in Cincinnati or Dayton during the 1999 heat wave, summarizes heat
      related deaths in the United States during 1979-1997, describes risk factors
      associated with heat-related illness and death, and recommends preventive
      measures.

PMID- 10882295
TI  - EGF and its receptor: historical perspective. Introduction.

PMID- 10882297
TI  - EGF-related peptides and their receptors in mammary gland development.
AB  - The discovery of multiple EGF-like ligands and erbB receptors offers the
      potential for a highly diverse signaling system allowing specific ligand/receptor
      complexes to be created in response to a certain hormone(s) or stage of mammary
      development. The known erbB receptors and several of the erbB-related ligands are
      synthesized by the normal mammary gland and have different temporal and spatial
      expression patterns. For instance, cumulative findings support the concepts that
      the EGF receptor has an essential role in morphogenesis of the mammary gland and
      that activation of this receptor occurs in response to estradiol-stimulated
      synthesis of an EGF receptor ligand in mammary stromal cells. The importance of
      both epithelial and stromal mammary cells in the hormonal activation of erbB
      related pathways is underscored in this review. Current experimental protocols
      that utilize erbB mutant mice or enable detection of phosphorylated erbB members
      and their proximal substrates should permit more precise identification of the
      pathways operative in the mammary gland.

PMID- 10882296
TI  - ErbB receptors and EGF-like ligands: cell lineage determination and oncogenesis
      through combinatorial signaling.
AB  - The ErbB/HER family of transmembrane receptor tyrosine kinases includes four
      members that bind more than two dozens ligands sharing an epidermal growth factor
      (EGF)3 like motif. This family plays a pivotal role in cell lineage
      determination in a variety of tissues, including mesenchyme-epithelial inductive
      processes and the interactions between neurons and muscle, glia and Schwann
      cells. Certain ligands and receptors of the family, especially the ErbB-2
      receptor tyrosine kinase, contribute to a relatively virulent phenotype of some
      human tumors; most notable are carcinomas of secretory epithelia. This large
      variety of biological signals is generated through a combinatorial network of
      signal transduction in which different ErbB ligands are apparently capable of
      stabilizing discrete homo- and heterodimeric receptor complexes, each coupled to
      a specific set of cytoplasmic signaling proteins. Because each receptor is unique
      in terms of catalytic activity, cellular routing and transmodulation, the
      resulting network allows not only an enormous potential for signal
      diversification but also fine tuning and stringent control of cellular functions.
      ErbB-2 emerges as a master coordinator of the network, prolonging and amplifying
      signaling by decelerating the dissociation rates of its heterologous ligands.
      Thus, the tumorigenic action of ErbB-2 may be attributed to its ability to act as
      a shared signaling subunit, rather than by functioning as a bone fide receptor.

PMID- 10882298
TI  - Transgenic mice reveal roles for TGFalpha and EGF receptor in mammary gland
      development and neoplasia.
AB  - Transforming growth factor-alpha (TGFalpha)4 and/or the EGF receptor (EGFR) are
      frequently overexpressed by human and rodent breast tumors, as well as tumor
      derived cell lines. Additionally, various observations suggest a role for
      TGFalpha and the EGFR signaling system in normal mouse mammary gland development.
      Recently, several laboratories have established TGFalpha transgenic mice with
      which to study the role of this growth factor in normal and neoplastic mammary
      biology. Examination of these mice revealed that overexpression of TGFalpha has
      profound consequences for this tissue. Most strikingly, transgenic mice
      expressing TGFalpha under the control of tissue-specific and nonspecific
      promoters stochastically developed focal mammary tumors with an incidence and
      latency that was markedly affected by pregnancy. Most TGFalpha-induced tumors
      were well-differentiated adenomas/adenocarcinomas, although some were
      undifferentiated and locally invasive. Distant metastases were only occasionally
      observed. Administration of the genotoxic carcinogen, 7,12-dimethylbenzanthracene
      (DMBA), dramatically accelerated mammary tumorigenesis induced by the TGFalpha
      transgene, raising the possibility that TGFalpha acts as a promoter in this
      tissue. Mice harboring dual transgenes encoding TGFalpha and either wild-type
      ERBB2 or c-myc displayed markedly accelerated tumorigenesis compared to mice
      carrying any of the single transgenes alone, indicative of potent cooperativity.
      Moreover, tumorigenesis in the bitransgenic mice was less dependent on pregnancy,
      and tumors were generally more malignant in appearance. Finally, TGFalpha also
      affected mammary gland dynamics. TGFalpha transgenic mice consistently displayed
      precocious alveolar development, were variably impaired with respect to
      lactation, and showed markedly reduced postlactional involution. As a result, the
      glands of multiparous females accumulated hyperplastic lesions that generally
      resembled milk-producing alveoli. Limited data support the hypothesis that these
      lesions were precursors to TGFalpha-induced tumors. In summary, these various
      findings underscore the potential importance of TGFalpha for cellular
      differentiation and transformation in the mammary gland. They also establish
      TGFalpha transgenic mice as a powerful model with which to study the role of EGFR
      signaling molecules in this dynamic tissue.

PMID- 10882299
TI  - The epidermal growth factor receptor in breast cancer.
AB  - The epidermal growth factor receptor (EGFR)3 is a 170 kD transmembrane tyrosine
      kinase activated by several ligands. It is required for normal mammary
      development and lactation and is aberrantly expressed in approximately 40% of
      breast carcinomas, particularly those with a poor prognostic phenotype. Since EGF
      receptor levels are elevated in a high proportion of many tumor types its
      potential as a therapy target is being investigated using the EGF receptor to
      target toxins, as well as drugs that interfere with signaling and anti-receptor
      antibodies. These approaches are likely to be most effective when used in the
      adjuvant situation in combination with chemotherapy.

PMID- 10882300
TI  - EGF-related peptides in the pathophysiology of the mammary gland.
AB  - Normal mammary gland development is the result of complex interactions between a
      number of hormones and growth factors. Normal and malignant human mammary
      epithelial cells are able to synthesize and to respond to various different,
      locally acting growth factors and growth inhibitors. Among these, the EGF-related
      peptides play an important role in regulating the proliferation and
      differentiation of human mammary epithelial cells. EGF4 and TGF4 are able to
      stimulate the lobulo-alveolar development of the mammary gland in vivo as well
      they are involved in the pathogenesis of human breast cancer. Experimental
      evidence suggests that estrogen-induced proliferation of breast carcinoma cells
      is mediated in part by EGF-related growth factors. It has also been demonstrated
      that activation of certain cellular protooncogenes such as c-Ha-ras in human
      mammary epithelial cells results in cellular transformation and in an increased
      production of several EGF-related growth factors such as TGFalpha and
      amphiregulin. Coexpression of both EGF-related peptides and their own receptors
      frequently occurs in human breast carcinomas and in human breast cancer cell
      lines, suggesting that an autocrine pathway of uncontrolled cell growth sustains
      neoplastic transformation.

PMID- 10882301
TI  - Transcriptional regulation of type I receptor tyrosine kinases in the mammary
      gland.
AB  - The transcriptional regulation of the human EGFR3 and ERBB2 genes has been
      extensively studied, particularly in the context of their overexpression in
      breast cancer. Here we summarize published work detailing the transcription
      factors which interact with the promoters of these and the rat ERBB2 homologue,
      neu, genes and discuss their possible relevance to gene activation in cancer. In
      addition we review the biologically significant molecules which modulate
      expression of these genes and discuss the nuclear factors involved in mediating
      these responses. We also describe novel therapies which may result from these
      studies and highlight directions for future research into the control of
      expression of the EGFR and ERBB2 genes in the normal mammary gland and in breast
      cancer.

PMID- 10882302
TI  - Type I receptor tyrosine kinases as targets for therapy in breast cancer.
AB  - Breast carcinomas express high levels of type I tyrosine kinase receptors and
      their ligands. For these reason therapies directed at these receptors have the
      potential to be useful anticancer agents. A series of monoclonal antibodies
      (MAbs)3 directed against the EGF receptor and the closely related erbB2/HER2/neu
      receptor are currently under evaluation. These MAbs have shown promising
      preclinical activity and "chimeric" and "humanized" MAbs have been produced in
      order to obviate the problem of host immune reactions. These antibodies are
      currently being tested in clinical trials either alone or in combination with
      chemotherapeutic agents. Clinical activity with anti-HER2/neu MAbs has been
      documented in patients with advanced breast cancer. In addition, compounds that
      inhibit receptor tyrosine kinases have shown significant preclinical activity and
      are potential candidates for clinical testing.

PMID- 10882305
TI  - Perspectives on the EGF family and the mammary gland.

PMID- 10882303
TI  - Hormonal regulation of type I receptor tyrosine kinase expression in the mammary
      gland.
AB  - Hormones guide mammary gland development and differentiation by regulating the
      expression of local growth factors and their receptors at the cell surface. In
      line with this principle the expression of the epidermal growth factor receptor
      (EGFR)3 and ErbB2 receptors varies in the mammary gland during pregnancy,
      following the changing hormonal profile. In breast cancer, expression of EGFR and
      ErbB2 is clearly related to the absence of estrogen and progesterone receptors.
      In breast cancer cells in vitro, the expression of these receptors is modulated
      by hormones and other growth-modulatory reagents. Moreover, transcriptional
      regulation of both EGFR and ERBB2 by estrogens has been demonstrated. The action
      of hormones may therefore result in the differential availability of individual
      ErbB family members at the cell surface, in this way determining the specific
      response of the cell to EGF-like factors and heregulins.

PMID- 10882304
TI  - Roles of ErbB-3 and ErbB-4 in the physiology and pathology of the mammary gland.
AB  - ErbB-3 and ErbB-4 are the most recently discovered and least characterized of the
      class I tyrosine kinase receptors. ErbB-3 is noteworthy for its low tyrosine
      kinase activity, suggesting that it may function more as an adaptor in signaling
      than as a kinase. Heregulin serves as a ligand for both receptors. A primary
      mechanism of heregulin action involves heterodimerization of its targeted
      receptors with other members of the class I family to promote cross
      phosphorylation and cellular responses. Betacellulin also acts as a ligand for
      ErbB-4 to stimulate its kinase activity in both homo- and hetero-dimers. A new
      ligand (ASGP-2) for ErbB-2 has been discovered which operates by an intramembrane
      mechanism and may be able to modulate external ligand-dependent ErbB-3 or ErbB-4
      heterodimeric interactions with ErbB-2. Heterodimerization stimulated by the
      ligands is a key feature of mitogenic signaling in mammary epithelial cells and
      tumors. Characterization of the signaling pathways for these receptors is still
      incomplete, but phosphatidylinositol 3-kinase and SHC have been implicated.
      Heregulin synthesized by the mesenchyme has been implicated in mammary
      development, modulated by systemic hormones. Observations on cultured mammary
      cells and mammary tumors have suggested linkages of ErbB-3 and ErbB-4 to
      proliferation and differentiation, respectively, but further work is needed to
      establish their definitive roles.

PMID- 10882306
TI  - Lactation in whales and dolphins: evidence of divergence between baleen- and
      toothed-species.
AB  - Although it has been more than one hundred years since the first publication on
      the milks of whales and dolphins (Order Cetacea), information on lactation in
      these species is scattered and fragmentary. Yet the immense size of some
      cetaceans, and the recent evidence that another group of marine mammals, the true
      seals, have remarkable rates of secretion of milk fat and energy, make this group
      of great comparative interest. In this paper information on lactation patterns,
      milk composition and lactation performance is reviewed. Two very different
      patterns are evident. Many of the baleen whales (Suborder Mysticeti) have
      relatively brief lactations (5-7 months) during which they fast or eat relatively
      little. At mid-lactation they produce milks relatively low in water (40-53%),
      high in fat (30-50%), and moderately high in protein (9-15%) and ash (1.2-2.1%).
      From mammary gland weights and postnatal growth rates, it is predicted that their
      energy outputs in milk are exceptional, reaching on the order of 4000 MJ/ d in
      the blue whale. This is possible because pregnant females migrate to feeding
      grounds where they can ingest and deposit great amounts of energy, building up
      blubber stores prior to parturition. On the other hand, the toothed whales and
      dolphins (Suborder Odontoceti) have much more extensive lactations typically
      lasting 1-3 years, during which the mothers feed. At mid-lactation their milks
      appear to be higher in water (60-77%) and lower in fat (10-30%) and ash (0.6
      1.1%), with similar levels of protein (8-11%). At least some odontocetes resemble
      primates in terms of low predicted rates of energy output and a long period of
      dependency of the young. However, these hypotheses are based on small numbers of
      samples for a relatively small number of species. Much of the available data on
      milk composition is of rather poor quality; for example, it is not possible to
      determine if milk composition changes over the course of lactation among
      odontocetes. Additional research on cetacean mammary glands and their secretions
      is needed to understand the reproductive strategies of these fascinating animals.

PMID- 10882307
TI  - Adaptations of maternal adipose tissue to lactation.
AB  - The ability to store substantial amounts of energy as lipid in adipose tissue has
      allowed development of a variety of strategies in wild animals to meet the
      considerable metabolic challenge of lactation. The ability to use adipose tissue
      energy has also been critical for development of the exceptional rates of milk
      production achieved in the dairy cow. Lactation thus results in profound changes
      in adipose tissue metabolism, the molecular bases of which are beginning to be
      resolved in domestic ruminants and laboratory rodents. In addition to its role as
      an energy store, adipose tissue has a variety of other functions (e.g.,
      modulation of mammary development, appetite, immune system function), some of
      which are important for lactation.

PMID- 10882308
TI  - Adaptation of the maternal intestine during lactation.
AB  - One of the most dramatic adaptations to lactation is a large increase in the size
      and complexity of maternal intestine. Although there are few data on changes in
      intestinal size, intestinal enlargement has been observed in many taxonomic
      groups. In this review I describe the morphological and physiological changes in
      the intestinal mass of lactating animals and discuss their functional
      significance. The observed increases maintain the digestive efficiency of the
      food, as well as insure adequate absorption of nutrients in the face of the
      increased energy demand that accompanies lactation. The extent of the increase in
      size is proportional to the increase in energy demand. It is clear that if the
      intestine did not accommodate during lactation mothers would not have the
      capacity to absorb the nutrients need to maintain their energy demand.

PMID- 10882309
TI  - Calcium and vitamin D metabolism during lactation.
AB  - Calcium transfer to the fetus in late pregnancy and the subsequent transfer of
      calcium to milk represent the greatest challenges to calcium homeostasis in adult
      animals. The adaptation of the maternal calcium homeostatic mechanisms is the
      result of a complex interplay between calciotropic hormones and the tissues,
      intestine, bone, and kidney, responsible for providing the large amounts of
      calcium needed to support fetal skeletal growth and lactation. In this review, we
      will discuss general calcium homeostasis followed by a review of the specific
      adaptations required by the human, rat, and cow to meet fetal and lactational
      demands for calcium. Finally, we will review what is known about the regulation
      of calcium transfer from the plasma to the milk.

PMID- 10882310
TI  - Adaptations of glucose metabolism during pregnancy and lactation.
AB  - Increased glucose requirements of the gravid uterus during late pregnancy and
      even greater requirements of the lactating mammary glands necessitate major
      adjustments in glucose production and utilization in maternal liver, adipose
      tissue, skeletal muscle, and other tissues. In ruminants, which at all times rely
      principally on hepatic gluconeogenesis for their glucose supply, hepatic glucose
      synthesis during late pregnancy and early lactation is increased to accommodate
      uterine or mammary demands even when the supply of dietary substrate is
      inadequate. At the same time, glucose utilization by adipose tissue and muscle is
      reduced. In pregnant animals, these responses are exaggerated by moderate
      undernutrition and are mediated by reduced tissue sensitivity and responsiveness
      to insulin, associated with decreased tissue expression of the insulin-responsive
      facilitative glucose transporter, GLUT4. Peripheral tissue responses to insulin
      remain severely attenuated during early lactation but recover as the animal
      progresses through mid lactation. Specific homeorhetic effectors of decreased
      insulin-mediated glucose metabolism during late pregnancy have yet to be
      conclusively identified. In contrast, somatotropin is almost certainly a
      predominant homeorhetic influence during lactation because its exogenous
      administration causes specific changes in glucose metabolism (and many other
      functions) of various nonmammary tissues which faithfully mimic normal
      adaptations to early lactation.

PMID- 10882311
TI  - Maternal folate status and lactation.
AB  - Folate plays an essential role in DNA, RNA, and protein biosynthesis. For this
      reason, the physiological need for this vitamin is increased during periods of
      rapid anabolic activity such as pregnancy and lactation. Although the importance
      of folate and the consequences of suboptimal folate status during pregnancy,
      especially during the periconceptional period, are well appreciated, little is
      known about the value of folate during lactation. The limited number of studies
      available on folate intake during lactation suggest that many women do not
      consume an adequate amount of folate and that recommended target intakes may be
      too low. Although inadequate maternal folate intake does not affect milk folate
      concentration unless maternal deficiency is severe, potential consequences of
      suboptimal folate nutrition to both the mother and her future offspring should
      also be considered.

PMID- 10882313
TI  - The tammar wallaby: a model to study putative autocrine-induced changes in milk
      composition.
AB  - The marsupial newborn is immature and the mother has the capacity to alter milk
      composition significantly during lactation, presumably to meet the nutritional
      requirements of the developing young. Furthermore, macropodid marsupials may
      practice asynchronous concurrent lactation (ACL)7 whereby the mother provides
      milk which differs in all the major components from adjacent mammary glands for
      two young of different ages. This phenomenon suggests that local regulation of
      mammary function, in addition to endocrine stimuli, is likely to be important for
      controlling milk composition. This paper explores the possibility that changes in
      sucking patterns of the young represent the first step in a mechanism to signal
      the mammary gland for putative autocrine-induced changes in milk composition.

PMID- 10882312
TI  - Lactation and fertility.
AB  - In almost all mammals lactation, or more correctly the suckling stimulus, induces
      a period of infertility designed to provide the optimal birth spacing for
      survival of the offspring. The duration of lactational infertility depends on the
      sucking activity of the young with little evidence to support a role for
      nutritional status. Suckling disrupts the normal pulsatile pattern of
      hypothalamic gonadotrophin releasing hormone (GnRH)2 secretion resulting in
      reduced LH secretion from the pituitary. Secretion of FSH returns to its normal
      cyclic pattern early in lactation and ovarian follicles may develop under its
      influence. However, until suckling declines, the follicles fail to secrete
      amounts of estradiol adequate to stimulate an LH surge and ovulation. The
      suckling stimulus may affect GnRH secretion by affecting prolactin, opiate and
      dopaminergic tone in the hypothalamus but no unifying mechanism has yet been
      proposed convincingly. The birth spacing effects of breastfeeding in women have a
      profound effect on infant well-being, and breastfeeding still prevents more
      pregnancies than all forms of artificial contraception.

PMID- 10882314
TI  - Lactation and breast cancer risk.
AB  - Breast cancer is a common disease with few practical preventive measures. The
      recent evidence that lactation, like other reproductive experiences, is
      associated with a modest reduction in breast cancer risk is therefore of great
      interest. Overall, the reduction in risk appears to be about 20% for ever breast
      feeding and is even greater for women with histories of prolonged lactation, or
      who initiate breast feeding at young ages. In many studies this risk reduction
      seems to be limited to premenopausal women. It appears unlikely that this inverse
      association is attributable either to higher risk among women who use lactation
      suppressants or who have difficulty either starting or continuing breast feeding.
      While a strong or consistent protective effect of lactation on breast cancer risk
      has not been observed in some large and well conducted studies, this likely
      reflects the limited breast feeding practices among modern women. If early,
      exclusive and extended breast feeding is necessary to achieve a breast cancer
      risk reduction, future studies among U.S. women may be unable to clarify this
      association.

PMID- 10882315
TI  - On writing.

PMID- 10882316
TI  - An explanatory model of health promotion and quality of life in chronic disabling
      conditions.
AB  - BACKGROUND: Although previous studies have examined selected factors influencing
      health-promoting behaviors or quality of life, the complex interplay of these
      variables in persons with chronic disabling conditions has not been investigated.
      OBJECTIVE: To test an explanatory model of variables influencing health promotion
      and quality of life (Stuifbergen & Rogers, 1997) in persons living with the
      chronic disabling condition of multiple sclerosis (MS). METHODS: A sample of 786
      persons with MS (630 women and 156 men) completed a battery of instruments
      measuring severity of illness-related impairment, barriers to health-promoting
      behaviors, resources, self-efficacy, acceptance, health-promoting behaviors, and
      perceived quality of life. The proposed model was assessed and modified using the
      weighted least squares procedure (WLS), which is implemented by LISREL8 (Joreskog
      & Sorbom, 1993). RESULTS: The initial model was modified to obtain a recursive
      model with adequate fit, chi2 (8, N = 786) = 77, p < 0.05; GFI = 0.96; IFI =
      0.98; CFI = 0.98. The antecedent variables accounted for 58% of the variance in
      the frequency of health-promoting behaviors and 66% of the variance in perceived
      quality of life. The effects of severity of illness on quality of life were
      mediated partially by health-promoting behaviors, resources, barriers, self
      efficacy and acceptance. CONCLUSIONS: The final model supports the hypothesis
      that quality of life is the outcome of a complex interplay among contextual
      factors (severity of illness), antecedent variables (Stuifbergen & Rogers, 1997),
      and health-promoting behaviors. The strength of direct and indirect paths
      suggests that interventions to enhance social support, decrease barriers, and
      increase specific self-efficacy for health behaviors would result in improved
      health-promoting behaviors and quality of life. Further research using a
      longitudinal design is needed to clarify the effects of the interaction between
      health-promoting behaviors and trajectory of illness on quality of life for
      persons with chronic disabling conditions.

PMID- 10882317
TI  - A public health nursing early intervention program for adolescent mothers:
      outcomes from pregnancy through 6 weeks postpartum.
AB  - BACKGROUND: Adolescent pregnancy and parenting remain a major public concern
      because of their impact on maternal-child health and on the social and economic
      well-being of the nation. Federal welfare reform legislation has created an
      urgent need for community-based nursing intervention programs to improve health
      and social outcomes for disadvantaged adolescent mothers and to promote their
      self-sufficiency. OBJECTIVE: To evaluate the effects of an early intervention
      program (EIP) that uses a public health nursing model on health and social
      outcomes of adolescent mothers and their children and on the quality of mother
      child interaction. METHODS: Pregnant adolescents referred to a county health
      department were randomly assigned to an experimental (EIP) or control
      (traditional public health nursing [TPHN]) group. The sample included 121
      adolescents from predominantly minority and impoverished backgrounds who were
      followed from pregnancy through 6 weeks postpartum. Intense and comprehensive
      home visitation by public health nurses and preparation-for-motherhood classes
      were provided to adolescents in the EIP. Health outcomes were determined on the
      basis of medical record data. Other measures included maternal self-report on
      selected behaviors, nurse interviews, and the Nursing Child Assessment Teaching
      Scale (NCATS). RESULTS: Early findings indicate reduced premature birth and low
      birth-weight (LBW) rates for young mothers receiving both forms of public health
      nursing care. No significant differences between groups were found for infant
      birth weight or type of delivery. Infants in the EIP had significantly fewer
      total days of birth-related hospitalization and rehospitalization than those in
      the TPHN group during the first 6 weeks of life (chi2(1) = 6.41; p = 0.01).
      Adolescents in the EIP demonstrated significantly more positive educational
      outcomes (e.g., lower school dropout rates) than those in the TPHN group (chi2(1)
      = 6.76; p < 0.009). CONCLUSIONS: The early findings of this study demonstrate
      that pregnant adolescents benefit from both traditional and more intense public
      health nursing care in terms of prenatal and perinatal outcomes. The EIP was
      associated with decreased infant morbidity during the first 6 weeks of life and
      decreased maternal school dropout. Long-term outcomes for the EIP are being
      evaluated.

PMID- 10882318
TI  - Self-care strategies for symptom management in patients with chronic heart
      failure.
AB  - BACKGROUND: The troublesome symptoms experienced by patients with chronic heart
      failure are associated with diminished quality of life, frequent
      hospitalizations, and mortality. OBJECTIVES: To describe the symptoms experienced
      by patients with heart failure, to detail the self-care strategies used by these
      patients in managing their symptoms, and to categorize the self-care strategies.
      METHODS: Six focus groups were used with 23 patients who had heart failure, along
      with six focus groups with 18 family members of the patients. Data analysis was
      performed by transcription of audiotape recordings of the group sessions and
      review of field notes. RESULTS: The patients reported a large number of
      troublesome symptoms, many consistent with past empirical findings, but some not
      reported in previous studies. Self-care strategies to manage the symptoms
      clustered into 11 categories. CONCLUSIONS: Results from this study provided
      direction for future studies to (a) identify the prevalence, severity, and
      etiologies of the commonly reported symptoms, particularly cognitive impairment,
      loss of balance, and depression; (b) evaluate the emotions reported by women with
      heart failure; and (c) test the strategies as part of an intervention program to
      improve symptom management in patients with heart failure.

PMID- 10882319
TI  - Measuring organizational traits of hospitals: the Revised Nursing Work Index.
AB  - BACKGROUND: The organizational context in which nurses practice is important in
      explaining variation in patient outcomes, but research has been hampered by the
      absence of instruments to measure organizational attributes empirically.
      OBJECTIVES: To report on the development and utility of the Revised Nursing Work
      Index (NWI-R) in measuring characteristics of professional nursing practice
      environments. METHODS: The NWI-R was used in a national acquired immunodeficiency
      syndrome (AIDS) care study. The sample consisted of 40 units in 20 hospitals. Of
      these 20 hospitals, 10 provided AIDS care in both dedicated AIDS units and
      general medical units, thus introducing to the design an element of internal
      control. The remaining 10 hospitals were selected through a matching procedure.
      Three of the matched control hospitals were magnet hospitals. Nurses were
      recruited into the study if they worked at least 16 hours per week on the study
      unit. The nurses completed the NWI-R in addition to other measures. RESULTS: A
      response rate of 86% was attained. Response rates per unit ranged from 73% to
      100%. Cronbach's alpha was 0.96 for the entire NWI-R, with aggregated subscale
      alphas of 0.84 to 0.91. Validity of the NWI-R was demonstrated by the origin of
      the instrument, its ability to differentiate nurses who worked within a
      professional practice environment from those who did not, and its ability to
      explain differences in nurse burnout. CONCLUSION: The NWI-R has been found to
      capture organizational attributes that characterize professional nursing practice
      environments.

PMID- 10882320
TI  - Testing the reliability and validity of the Self-Efficacy for Exercise scale.
AB  - BACKGROUND: The measure for self-efficacy barriers to exercise was developed for
      adults and revised on the basis of quantitative and qualitative research with
      older adults so it would be more appropriate for that age group. OBJECTIVES: To
      test the reliability and validity of the Self-Efficacy for Exercise (SEE) Scale.
      METHODS: Initial reliability and validity testing was performed using a sample of
      187 older adults living in a continuing care retirement community. The average
      age of the participants was 85 +/- 6.2 years, and most were White (98%), female
      (82%), and unmarried (80%). Face-to-face interviews were completed and included
      the SEE, the 12-item Short Form Health Survey (SF-12), and the Expected Outcomes
      and Barriers for Habitual Exercise scale. Exercise activity was based on verbal
      report of participation in aerobic exercise (walking, swimming, biking, or
      jogging). RESULTS: There was sufficient evidence of internal consistency (alpha =
      0.92), and a squared multiple correlation coefficient using structural equation
      modeling provided further evidence of reliability (R2 ranged from 0.38 to 0.76).
      There was evidence of validity of the measure based on hypothesis testing: Mental
      and physical health scores on the SF-12 predicted efficacy expectations, and
      efficacy expectations predicted exercise activity. Lambda X estimates (all
      estimates > or = 0.81) provided further evidence of validity. CONCLUSION:
      Preliminary testing provided evidence for the reliability and validity of the SEE
      scale. Future testing of the scale needs to be done with young old adults and
      subjects from different socioeconomic and cultural groups.

PMID- 10882321
TI  - Risk factors for cardiovascular disease in children with Type I diabetes.
AB  - BACKGROUND: The major cause of morbidity and mortality in individuals with Type I
      insulin-dependent diabetes mellitus (IDDM) is premature and extensive
      atherosclerotic cardiovascular disease (CVD). OBJECTIVES: To determine the
      prevalence and predictors of hypercholesterolemia and to examine the distribution
      and interrelationship of risk factors for CVD. METHODS: This observational (mixed
      longitudinal) study, guided by an epidemiologic framework, assessed a sample of
      140 children with IDDM. Total cholesterol (TC) and diabetes control were measured
      in the total sample. Standard CVD risk factors were measured in a subsample of 67
      children. RESULTS: Observed frequency of TC greater than the 75th percentile and
      greater than the 95th percentile was significantly more than expected (p < 0.01
      and p < 0.0001, respectively). In the total sample, TC-CVD risk factor
      associations were not observed. However, diabetes control and physical activity
      were correlated with TC in the risk sample of children at highest risk, as
      demonstrated by hypercholesterolemia. CONCLUSIONS: Results demonstrate the
      importance of assessing the lipid profile in children with IDDM and monitoring
      CVD risk factors in hyperlipidemic children with IDDM. Future research should
      focus on prospective longitudinal studies in population-based multiethnic samples
      of children with IDDM.

PMID- 10882322
TI  - Concerns and risk factor modification in women during the year after coronary
      artery surgery.
AB  - BACKGROUND: Future plans or return to a usual lifestyle has been shown to be of
      concern to persons recovering from coronary artery surgery. However it is not
      clear whether early concerns remain stable or evolve over time. OBJECTIVE: To
      examine women's concerns about having coronary artery surgery and living with
      coronary artery disease after surgery over time. METHODS: Concerns and risk
      factor modification strategies were measured in 55 women at 1, 6, and 12 months
      after coronary artery surgery. The Carr and Powers Stressor Scale and an
      investigator-developed interview were used. RESULTS: Women's primary concerns
      shifted over the year from surgical recovery to living with coronary heart
      disease. At 1 month after surgery, issues related to future plans, such as
      progress in recovery and resuming lifestyle, were rated as causing the most
      concern. Concern about diet was the highest rated concern 1 year after surgery.
      More than half of the women reported exercising more, and approximately three
      fourths reported eating a better diet 1 year after surgery. CONCLUSIONS: The
      findings demonstrate that women are concerned about diet and exercise, and many
      women attempt to change their behavior. Capitalizing on women's concerns about
      living with coronary artery disease may help address risk factors. However,
      specialized interventions may be needed that focus on women who are not concerned
      about and/or not engaged in risk reduction behaviors.

PMID- 10882323
TI  - Data collection using handheld computers.

PMID- 10882324
TI  - Goal attainment scaling to measure individual change in intervention studies.

PMID- 10882325
TI  - Molecular-targeted anticancer therapy: challenges related to study design and
      choice of proper endpoints.

PMID- 10882326
TI  - Adjuvant high-dose interferon revisited.

PMID- 10882327
TI  - Use of immunotoxins in the treatment of lymphoma.

PMID- 10882328
TI  - Adjuvant high-dose interferon alfa-2b in patients with high-risk melanoma.
AB  - We performed an analysis of toxicity and survival in stage III melanoma patients
      receiving adjuvant interferon alfa-2b (IFN). This was a retrospective single-arm
      analysis of 40 patients with stage III melanoma who received (IFN) administered
      at maximum tolerated doses of 20 mU/m2/day intravenously (i.v.) for 1 month and
      10 mU/m2 three times per week subcutaneously (s.c.) for 48 weeks. Toxicity in our
      series is comparable to that experienced in the Eastern Cooperative Oncology
      Group (ECOG) 1684 trial, except for higher rates of dose-limiting
      myelosuppression and hepatotoxicity. All 40 patients experienced constitutional
      symptoms, but only 14/40 (35%) experienced grade 3 to 4 symptoms. Of the 40
      patients, 36 (90%) experienced neurologic symptoms, but only seven (17.5%)
      experienced grade 3 to 4 neurotoxicity. Two patients stopped treatment because of
      severe psychiatric symptoms; one patient attempted suicide, and a psychosis
      developed in another. Thirty-nine (97.5%) patients experienced myelosuppression;
      31 (77.5%) developing grade 3 to 4 myelosuppression. Hepatotoxicity was evident
      in 39 (97.5%) patients, and 26 (65%) experienced grade 3 to 4 hepatotoxicity.
      Three patients (7.5%) experienced mild renal toxicity. At a median follow-up of
      27 months from initiation of therapy, there have been 19 relapses (47.5% disease
      free survival [DFS]) and 10 deaths (75% OS) resulting from progression of
      disease. The DFS compares with the treatment arm in ECOG 1684 at 27 months, but
      overall survival is higher in our series of patients at the same time point. In a
      single program setting, IFN can be administered with similar side effects and
      outcome profiles seen in multi-institutional studies. Modifications in the
      induction regimen resulted in notably higher hematologic and hepatic toxicities
      but did not preclude administering further therapy and did not result in
      increased attrition rate among patients: only nine patients (22.5%) had their
      treatment stopped as a result of IFN-related toxicity. In comparison, 26% of
      patients had to have their treatment discontinued because of toxicity in ECOG
      1684.

PMID- 10882329
TI  - Combination chemotherapy followed by an immunotoxin (anti-B4-blocked ricin) in
      patients with indolent lymphoma: results of a phase II study.
AB  - The purpose of this article was to evaluate the antitumor effects of a
      combination chemotherapy program based on ProMACE (prednisone, methotrexate,
      doxorubicin [Adriamycin], cyclophosphamide, etoposide) followed by a B cell
      specific immunotoxin in the treatment of patients with advanced-stage indolent
      histology non-Hodgkin's lymphomas. We performed a prospective phase II clinical
      trial in a referral-based patient population. After confirmation of diagnosis and
      staging evaluation, 44 patients (10 small lymphocytic lymphoma, 27 follicular
      lymphoma, 7 mantle cell lymphoma; 30 without prior therapy, 14 previously
      treated) received six cycles of ProMACE-CytaBOM (cytarabine, bleomycin,
      vincristine [Oncovin], mechlorethamine) combination chemotherapy (with etoposide
      given orally daily for five days) followed by a 7-day continuous infusion of anti
      B4-blocked ricin immunotoxin at 30 microg/kg/day given every 14 days for up to
      six cycles. A complete response was achieved in 25 of 44 patients (57%), 21 from
      the chemotherapy alone, 3 converted from partial to complete response with the
      immunotoxin, and 1 patient became a complete responder after a surgical procedure
      to remove an enlarged spleen that was histologically negative for lymphoma. With
      a median follow-up of 5 years, 14 of 25 complete responders have relapsed (56%);
      median remission duration was 2 years, and overall survival was 61%. Forty-two
      percent of the complete responders have been in continuous remission for more
      than 4 years. The median number of courses of immunotoxin delivered was two
      usually because of the development of human anti-ricin antibodies. ProMACE
      CytaBOM plus anti-B4-blocked ricin does not produce durable complete remissions
      in the majority of patients with indolent lymphoma. However, the remissions
      appear quite durable (> 4 years) in about 40% of the complete responders.

PMID- 10882330
TI  - Paclitaxel, carboplatin, and vinorelbine in the treatment of advanced non-small
      cell lung cancer: a phase II trial of the Minnie Pearl Cancer Research Network.
AB  - PURPOSE: To evaluate the feasibility, toxicity, and efficacy of adding
      vinorelbine to the paclitaxel/carboplatin combination in the treatment of
      advanced non-small cell lung cancer. PATIENTS AND METHODS: Patients with advanced
      (stage IIIB/IV) non-small cell lung cancer who had received no previous
      chemotherapy were treated with the following three-drug regimen: paclitaxel, 200
      mg/m2, 1-hour i.v. infusion, day 1; carboplatin, AUC 6.0 i.v., day 1; and
      vinorelbine, 22.5 mg/m2 i.v. days 1 and either 8 or 15. Treatment was repeated
      every 21 days. This phase II trial was conducted in a multicenter, community
      based setting. RESULTS: Eighty-nine patients were treated with a median of four
      courses of therapy (range, one to eight). Thirty-one patients (35%) had major
      responses (two complete, 29 partial), and 36 patients (40%) had a minor response
      or stable disease. Actuarial median survival was 8.6 months; 1 year survival was
      43%. Leukopenia was the major toxicity: 73% of patients had grade 3/4 toxicity,
      and 32 patients (36%) were hospitalized for neutropenia/fever (11% of total
      courses administered). Treatment-related death due to infection occurred in four
      patients (4%). CONCLUSIONS: This three-drug regimen is feasible and efficacious
      in the treatment of advanced non-small cell lung cancer. The addition of
      vinorelbine increases the incidence of severe leukopenia substantially when
      compared with the paclitaxel/carboplatin regimen. However, other toxicities are
      not markedly increased. Ongoing randomized trials will define the role of this
      regimen in the treatment of non-small cell lung cancer.

PMID- 10882331
TI  - Antiemetic efficacy of single-dose oral granisetron (1 mg vs 2 mg) with
      moderately emetogenic chemotherapy.
AB  - PURPOSE: To compare the efficacy of oral granisetron, 1 mg and 2 mg, administered
      as one dose in patients who receive moderately emetogenic chemotherapy. PATIENTS
      AND METHODS: Chemotherapy-naive patients, scheduled to receive intravenous
      cyclophosphamide (500 to 1200 mg/m2) or carboplatin (> or = 300 mg/m2), were
      stratified by dexamethasone/methylprednisolone use (+ DEX, n = 92) or nonuse (-
      DEX, n = 5). Patients were randomized to one dose of either 1 mg (n = 48) or 2 mg
      (n = 49) of granisetron administered 60 minutes before chemotherapy. Known
      important prognostic variables (gender, age, alcohol) were well balanced between
      groups. RESULTS: Using the most rigorous criterion of total control (no emetic
      episodes, no nausea, no rescue therapy during the first 24 hours), response rates
      were 54.2% (26/48) and 57.1% (28/49) in patients receiving 1 mg and 2 mg of
      granisetron, respectively (95% confidence interval, -0.17, 0.23). Total control
      rates in patients who received 1 mg and 2 mg of granisetron + DEX were also
      comparable: 57.8% (26/45) and 55.3% (26/47), respectively. Response rates were
      similar for the parameters of nausea, emesis, and complete response (no emetic
      episodes, no more than mild nausea, no antiemetic rescue). Among all patients,
      one (2.1%) who received 1 mg of granisetron and three (6.1%) who received 2 mg
      experienced severe nausea. The proportions of 1- and 2-mg-treated patients who
      received rescue therapy within the first 24 hours were 31.3% (15/48) and 34.7%
      (17/49), respectively. Reported adverse experiences were generally mild in
      severity. DISCUSSION: The results of this trial demonstrate good control of
      emesis with a single 1-mg dose of oral granisetron, with efficacy that compares
      favorably with that of a 2-mg dose.

PMID- 10882332
TI  - Treatment of ras-induced cancers by the F-actin-bundling drug MKT-077.
AB  - A rhodacyanine dye called MKT-077 has shown a highly selective toxicity toward
      several distinct human malignant cell lines, including bladder carcinoma EJ, and
      has been subjected to clinical trials for cancer therapy. In the pancreatic
      carcinoma cell line CRL-1420, but not in normal African green monkey kidney cell
      line CV-1, it is selectively accumulated in mitochondria. However, both the
      specific oncogenes responsible for its selective toxicity toward cancer cells,
      and its target proteins in these cancer cells, still remain to be determined.
      This study was conducted using normal and ras-transformed NIH 3T3 fibroblasts to
      determine whether oncogenic ras mutants such as v-Ha-ras are responsible for the
      selective toxicity of MKT-077 and also to identify its targets, using its
      derivative called "compound 1" as a specific ligand. We have found that v-Ha-ras
      is responsible for the selective toxicity of MKT-077 in both in vitro and in
      vivo. Furthermore, we have identified and affinity purified at least two distinct
      proteins of 45 kD (p45) and 75 kD (p75), which bind MKT-077 in v-Ha-ras
      transformed cells but not in parental normal cells. Microsequencing analysis has
      revealed that the p45 is a mixture of beta- and gamma-actin, whereas the p75 is
      HSC70, a constitutive member of the Hsp70 heat shock adenosine triphosphatase
      family, which inactivates the tumor suppressor p53. MKT-077 binds actin directly,
      bundles actin filaments by cross-linking, and blocks membrane ruffling. Like a
      few F-actin-bundling proteins such as HS1, alpha-actinin, and vinculin as well as
      F-actin cappers such as tensin and chaetoglobosin K (CK), the F-actin-bundling
      drug MKT-077 suppresses ras transformation by blocking membrane ruffling. These
      findings suggest that other selective F-actin-bundling/capping compounds are also
      potentially useful for the chemotherapy of ras-associated cancers.

PMID- 10882333
TI  - Decision analysis of tamoxifen for the prevention of invasive breast cancer.
AB  - PURPOSE: The recent Breast Cancer Prevention Trial has shown that tamoxifen may
      prevent invasive breast cancer. We used a Markov model to estimate the long-term
      effects of chemoprevention with tamoxifen on survival, quality-adjusted survival,
      and health care costs. METHODS: We used a hypothetical cohort of women with
      breast-cancer risk similar to that of participants in the Breast Cancer
      Prevention Trial, and a computer-based decision analysis (Markov model and 500
      Monte Carlo simulations) to model the outcomes of interest. Survival calculations
      were from Surveillance, Epidemiology, and End-Results (SEER) data; preference
      ratings from a time trade-off questionnaire administered to a group of average
      risk women; and cost estimates from the Group Health Cooperative of Puget Sound
      and the Health Care Financing Administration. We obtained utility measures for
      quality-adjustment by administering a time trade-off questionnaire to a group of
      community-based women. RESULTS: Use of tamoxifen prolonged the average survival
      of cohort members by 69 days (95% probability interval [PI] 27 to 117) for those
      who started use at age 35 years; 40 days (95% PI 16 to 67) for those who started
      use at age 50 years; and 27 days (95% PI 14 to 40) for those who started use at
      age 60 years. Tamoxifen extended quality-adjusted survival by 38 days (95% PI 0.1
      to 82) at age 35, 25 days (95% PI 0 to 50) at age 50, and 22 days (95% PI 5 to
      39) days at age 60. Chemoprevention with tamoxifen cost $46,619 (95% PI $27,928
      to $98,796) per life year life saved for women who started at age 35; for women
      over age 50, it cost more than $50,000 per life year saved. DISCUSSION: Tamoxifen
      use may improve long-term survival and quality-adjusted survival among women who
      are at increased risk of breast cancer, but this benefit diminishes with age.
      Tamoxifen is cost-effective in comparison with other cancer treatment strategies
      for younger women only.

PMID- 10882334
TI  - Nonmyeloablative allogeneic peripheral blood stem-cell transplantation as
      immunotherapy for malignant diseases.

PMID- 10882335
TI  - BRCA1 germline mutation presenting as an adenocarcinoma of unknown primary.
AB  - BACKGROUND: The work-up of adenocarcinoma of unknown primary usually includes
      history, physical examination, radiographic imaging, tumor markers, and more
      recently molecular and genetic information. We report here on how the suggestion
      by family history of a BRCA1 mutation guided the diagnostic and therapeutic
      approach in a patient with metastatic carcinoma of unknown primary. METHODS:
      BRCA1 mutation was screened for by polymerase chain reaction (PCR) and single
      strand conformational polymorphism analysis. Primers for PCR amplification
      included selected BRCA1 exons 2, 110, 11L, 13, and 20. The PCR product was cloned
      into a PCRII vector and sequenced with a Sequenase Version 2.0 Sequencing Kit.
      RESULTS: Single-strand conformational polymorphism analysis suggested a mutation
      in the region of exon 20 and sequencing confirmed the presence of a germline
      mutation 5382insC. CONCLUSIONS: This case illustrates an unusual presentation of
      adenocarcinoma of unknown primary in a patient with a germline BRCA1 mutation,
      the use of a suspected germline mutation to guide the work-up and treatment, and
      finally the value of positron emission tomography scanning in the work-up of an
      unknown primary.

PMID- 10882336
TI  - Low-density lipoprotein particle composition: what is the contribution to
      atherogenicity?

PMID- 10882337
TI  - Triglyceride synthesis: insights from the cloning of diacylglycerol
      acyltransferase.
AB  - Although the biochemistry of triglyceride synthesis has been studied for decades,
      an understanding of the molecular processes involved has been lacking. The recent
      cloning of a gene encoding acyl coenzyme A : diacylglycerol acyltransferase, an
      enzyme that catalyses the final step in triglyceride synthesis, has opened this
      area to molecular investigation and has begun to provide new insights into
      triglyceride metabolism.

PMID- 10882338
TI  - Responses to eating: lipoproteins, lipolytic products and atherosclerosis.
AB  - Several lines of clinical and experimental data suggest that postprandial lipemia
      is an independent risk factor for atherosclerosis. There are a number of reasons
      why processes that occur in the period immediately after eating could be
      deleterious to arteries. By understanding the links between postprandial lipemia
      and the accumulation of lipid within vessels, a more global understanding of how
      lipoproteins cause disease may be forthcoming. In this article recent information
      on the control of postprandial lipemia and the biological effects of chylomicron
      remnants and lipolysis products will be reviewed. Because this topic is broad, we
      will focus on the roles played by lipoprotein lipase and proteoglycans in this
      process.

PMID- 10882339
TI  - Apolipoprotein E and atherosclerosis.
AB  - Apolipoprotein E plays a key protective role in atherosclerosis. Its capacity to
      safeguard against this disease can be attributed to at least three distinct
      functions. First, plasma apolipoprotein E maintains overall plasma cholesterol
      homeostasis by facilitating efficient hepatic uptake of lipoprotein remnants.
      Second, lesion apolipoprotein E in concert with apolipoprotein A-I facilitates
      cellular cholesterol efflux from macrophage foam cells within the intima of the
      lesion. Third, lesion apolipoprotein E directly modifies both macrophage- and T
      lymphocyte-mediated immune responses that contribute to this chronic inflammatory
      disease.

PMID- 10882340
TI  - ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL
      apolipoproteins.
AB  - Lipid-poor apolipoproteins remove cellular cholesterol and phospholipids by an
      active transport pathway controlled by an ATP binding cassette transporter called
      ABCA1 (formerly ABC1). Mutations in ABCA1 cause Tangier disease, a severe HDL
      deficiency syndrome characterized by a rapid turnover of plasma apolipoprotein A
      I, accumulation of sterol in tissue macrophages, and prevalent atherosclerosis.
      This implies that lipidation of apolipoprotein A-I by the ABCA1 pathway is
      required for generating HDL particles and clearing sterol from macrophages. Thus,
      the ABCA1 pathway has become an important therapeutic target for mobilizing
      excess cholesterol from tissue macrophages and protecting against
      atherosclerosis.

PMID- 10882341
TI  - Stable isotope turnover of apolipoproteins of high-density lipoproteins in
      humans.
AB  - Amino acid precursors labelled with stable isotopes have been successfully used
      to explore the metabolism of the apolipoproteins of HDL. Some methodological and
      mathematical modelling problems remain, mainly related to amino acid recycling in
      a plasma protein such as apolipoprotein A-I with a long residence time (the
      reciprocal of the fractional catabolic rate) of 4-5 days. Apolipoprotein A-I,
      apolipoprotein E, and apolipoprotein A-IV in triglyceride-rich lipoproteins
      (containing chylomicrons, VLDL, and remnants) exhibit more complex kinetics. The
      small amounts of apolipoprotein A-I and of apolipoprotein A-IV in the
      triglyceride-rich lipoproteins have a residence time similar to that of the
      apolipoprotein A-I of HDL. In contrast, the apolipoprotein E in triglyceride-rich
      lipoproteins has been found to have an average residence time of 0.11 days. Diets
      low in saturated fat and cholesterol, which lower HDL levels, do so by decreasing
      the secretion of apolipoprotein A-I, with apolipoprotein A-II kinetics
      unaffected. Individuals with impaired glucose tolerance have a decreased
      residence time of apolipoprotein A-I but no change in secretion rate or in
      apolipoprotein A-II kinetics. This suggests a link between insulin resistance and
      the risk of atherosclerosis. In heterozygous familial hypercholesterolemia, both
      the fractional catabolic rate and the secretion rate of apolipoprotein A-I are
      increased, resulting in no change in the plasma level. Stable isotope studies
      have strengthened the evidence that triglyceride enrichment of HDL increases its
      catabolism Laboratory.

PMID- 10882342
TI  - Lecithin-cholesterol acyltransferase: role in lipoprotein metabolism, reverse
      cholesterol transport and atherosclerosis.
AB  - In the past several years significant advances have been made in our
      understanding of lecithin-cholesterol acyltransferase (LCAT) function. LCAT
      beneficially alters the plasma concentrations of apolipoprotein B-containing
      lipoproteins, as well as HDL. In addition, its proposed role in facilitating
      reverse cholesterol transport and modulating atherosclerosis has been
      demonstrated in vivo. Analysis of LCAT transgenic animals has established the
      importance of evaluating HDL function, as well as HDL plasma levels, to predict
      atherogenic risk.

PMID- 10882343
TI  - Hepatic lipase and HDL metabolism.
AB  - Hepatic lipase is a lipolytic enzyme that has been suggested to have a role in
      HDL metabolism. Evidence suggests that HDL-cholesterol level is at least partly
      regulated by hepatic lipase level. Recent studies have shown that hepatic lipase
      not only hydrolyzes triglyceride and phospholipid in HDL, but also stimulates HDL
      cholesterol ester uptake by hepatocytes. Therefore, hepatic lipase, together with
      lipid transfer proteins, determines both HDL-cholesterol level and its function
      in reverse cholesterol transport. These conclusions are based on observations
      from in-vitro model substrate studies, cell culture studies, transgenic animal
      studies, and clinical studies. At present time, it is not known whether hepatic
      lipase action increases or decreases risk of developing atherosclerosis.

PMID- 10882344
TI  - Phospholipid transfer protein in lipid metabolism.
AB  - Phospholipid transfer protein (PLTP) is one of the main modulators of plasma HDL
      size and composition. The publications discussed in the present review have
      substantially increased our knowledge on the physiological importance of PLTP
      mediated phospholipid transfer, especially between triglyceride-rich lipoproteins
      and HDL. Furthermore, novel data have provided clues about the transfer
      mechanism, and evidence for the direct involvement of PLTP in atheroprotection
      has recently been presented. The development of assays for PLTP mass
      determination has offered new tools for the elucidation of the physiological role
      of PLTP.

PMID- 10882345
TI  - Of mice and men (and women) and the acylation-stimulating protein pathway.
AB  - The storage and release of energy by adipocytes is of fundamental biologic
      importance. Not surprisingly, therefore, the rate at which these processes occur
      can be modulated by a variety of physiologic molecules. A newly recognized
      participant is produced by adipocytes themselves: acylation-stimulating protein
      (ASP). This article focuses on the most recent in-vivo evidence regarding how the
      ASP pathway may influence energy storage and release. In brief, the rate at which
      triglycerides are cleared from plasma (i.e. the rate at which they are
      hydrolysed) is determined by lipoprotein lipase and insulin, which is the
      principal hormone that regulates lipoprotein lipase. By contrast, the ASP pathway
      modulates the rate at which fatty acids are taken up and converted to
      triglycerides by adipocytes. Under certain circumstances, however, reduction of
      activity of the ASP pathway may negatively impact on the first step of the
      process. ASP also influences the rate at which fatty acids are released by
      adipocytes, and it is clear that insulin and ASP interact in a variety of ways
      that involve energy storage and release. Accordingly, to understand the impact of
      any intervention on energy storage and release by adipocytes, the effects of both
      insulin and ASP must be taken into account.

PMID- 10882346
TI  - Physiological aspects of low-density lipoprotein oxidation.
AB  - The oxidation of LDL is thought to be a major contributor to the development of
      atherosclerosis. Considerable descriptive evidence has been accumulated showing
      that oxidized LDL promotes pro-atherogenic events. However, direct evidence that
      oxidized LDL causes atherosclerosis is lacking. This article summarizes the
      results of recent studies that demonstrate how oxidized LDL affects cellular
      function, and highlights key issues that should be addressed to link LDL
      oxidation with atherosclerosis.

PMID- 10882347
TI  - Bibiliography. Current world literature. Lipid metabolism.

PMID- 10882348
TI  - Nutrition and therapeutics.

PMID- 10882349
TI  - Genetics and molecular biology.

PMID- 10882350
TI  - Lipid metabolism.

PMID- 10882351
TI  - Hyperlipidaemia and cardiovascular risk factors.

PMID- 10882352
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 10882353
TI  - Therapy and clinical trials.

PMID- 10882354
TI  - Structure-based design and synthesis of a potent matrix metalloproteinase-13
      inhibitor based on a pyrrolidinone scaffold.

PMID- 10882355
TI  - Fenchylamine sulfonamide inhibitors of amyloid beta peptide production by the
      gamma-secretase proteolytic pathway: potential small-molecule therapeutic agents
      for the treatment of Alzheimer's disease.

PMID- 10882356
TI  - A 3D-QSAR study on the structural requirements for binding to CB(1) and CB(2)
      cannabinoid receptors.
AB  - A 3D-QSAR study was carried out on 20 cannabinoids for which the binding
      affinities (K(i)) with respect to CB(1) and CB(2) receptors, determined in the
      same cell line, were available. For the first time three series of significantly
      different chemical structures such as Delta(9)-THC analogues, anandamides, and
      indoles were included in a single 3D-QSAR model, to obtain information on the
      interactions of all ligands with both CB(1) and CB(2) receptors and on their
      receptor selectivity. Delta(9)-THC was chosen as the structural template for
      alignment. The 3D-structure-activity correlation obtained by the GOLPE procedure
      provided a partial least squares (PLS) model with a very good predictive ability
      for the CB(1) receptor affinity of all compounds. The model allowed us to
      identify seven different regions in the space that contribute to explain the
      above binding affinities. External validation of the interpretation of the 3D
      QSAR model was derived from a response-independent procedure such as principal
      components analysis (PCA). The CB(2) receptor model evidenced, besides the seven
      regions found for the CB(1) receptor, a new characteristic region for the CB(2)
      receptor. Another PCA, using 10 GRID probes, provided further evidence of
      receptor selectivity regions. One region opposite to the amidic NH of CB(1)
      selective O585 appears to be responsible for the CB(1) selectivity, while an
      interaction region opposite to the carbonyl of CB(2) selective JWH-015 appears to
      be involved in the CB(2) binding selectivity.

PMID- 10882357
TI  - New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF
      receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis.
AB  - The sprouting of new blood vessels, or angiogenesis, is necessary for any solid
      tumor to grow large enough to cause life-threatening disease. Vascular
      endothelial growth factor (VEGF) is one of the key promoters of tumor induced
      angiogenesis. VEGF receptors, the tyrosine kinases Flt-1 and KDR, are expressed
      on vascular endothelial cells and initiate angiogenesis upon activation by VEGF.
      1-Anilino-(4-pyridylmethyl)-phthalazines, such as CGP 79787D (or PTK787 /
      ZK222584), reversibly inhibit Flt-1 and KDR with IC(50) values < 0.1 microM. CGP
      79787D also blocks the VEGF-induced receptor autophosphorylation in CHO cells
      ectopically expressing the KDR receptor (ED(50) = 34 nM). Modification of the 1
      anilino moiety afforded derivatives with higher selectivity for the VEGF receptor
      tyrosine kinases Flt-1 and KDR compared to the related receptor tyrosine kinases
      PDGF-R and c-Kit. Since these 1-anilino-(4-pyridylmethyl)phthalazines are orally
      well absorbed, these compounds qualify for further profiling and as candidates
      for clinical evaluation.

PMID- 10882358
TI  - Hydroxamic acid derivatives as potent peptide deformylase inhibitors and
      antibacterial agents.
AB  - Low-molecular-weight beta-sulfonyl- and beta-sulfinylhydroxamic acid derivatives
      have been synthesized and found to be potent inhibitors of Escherichia coli
      peptide deformylase (PDF). Most of the compounds synthesized and tested displayed
      antibacterial activities that cover several pathogens found in respiratory tract
      infections, including Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus
      influenzae, and Moraxella catarrhalis. The potential of these compounds as
      antibacterial agents is discussed with respect to selectivity, intracellular
      concentrations in bacteria, and potential for resistance development.

PMID- 10882359
TI  - 17beta-O-Aminoalkyloximes of 5beta-androstane-3beta,14beta-diol with digitalis
      like activity: synthesis, cardiotonic activity, structure-activity relationships,
      and molecular modeling of the Na(+),K(+)-ATPase receptor.
AB  - A series of digitalis-like compounds with a 17-aminoalkoxyiminoalkyl or -alkenyl
      substituent was synthesized and evaluated for inhibition of Na(+),K(+)-ATPase and
      for inotropic activity. The highest inhibition was found with compounds having
      the substituent in configuration 17beta and the amino group at a distance of 6 or
      7 bonds from C(17) of the digitoxigenin skeleton. The presence of the oxime
      function strengthens the interaction with the receptor, more if alpha,beta
      unsaturated, thus mimicking the electronic situation of the unsaturated lactone
      in natural digitalis compounds. The most active compounds showed Na(+),K(+)
      ATPase inhibitory potencies (IC(50)) 17-25 times higher than the standards
      digitoxigenin and digoxin and 3-11 times higher inotropic potencies (EC(50)) in
      isolated guinea pig left atria. These features are supported by a molecular model
      suggesting the possible interactions of the groups described above with
      particular amino acid residues in the H1-H2 domains of Na(+),K(+)-ATPase. Some
      interactions are the classical ones already described in the literature; a new,
      very strong interaction of the basic group with the Cys138 was found and adds new
      possibilities to design compounds interacting with this region of the receptor.
      The most interesting compounds were also studied in vivo in the anesthetized
      guinea pig for evaluating their inotropic effect versus the lethal dose.
      Compounds 9 and 12 showed a slightly higher safety ratio than digoxin and deserve
      further evaluation.

PMID- 10882360
TI  - CCK peptides with combined features of hexa- and tetrapeptide CCK-A agonists.
AB  - Selective CCK-A agonist activity has been reported to induce satiety in a variety
      of animals, including man, and thereby suggests a therapeutic role for CCK in the
      management of obesity. To date, three general classes of CCK-A agonists have been
      reported, the full-length, sulfated hepta- and hexapeptides, a series of
      tetrapeptides, and most recently a series of benzodiazepines. The SAR of the hexa
      and tetrapeptide classes suggests that the Hpa(SO(3)H) and Tac groups may not
      interact at the CCK-A receptor in the same location. However, the C-terminal
      dipeptide part of the hexapeptides and tetrapeptides appear to interact at the
      CCK-A receptor in a similar manner. Compound 7 (Hpa-Nle-Gly-Trp-Lys(Tac)-Asp
      MePhe-NH(2)) derived from combining the features of the hexapeptides and the
      tetrapeptides has subnanomolar affinity and 3500-fold selectivity for CCK-A
      receptors. Compound 7 administered intraperitoneally produces potent, long
      lasting reduction in food intake in rats and a corresponding weight loss when
      administered over nine consecutive days.

PMID- 10882361
TI  - Synthesis and biological evaluation of bombesin constrained analogues.
AB  - Analogues of bombesin which incorporate dipeptide or turn mimetics have been
      synthesized. One of them (compound 11) containing a seven-membered lactam ring
      revealed a good affinity for GRP/BN receptors on rat pancreatic acini (K(i) value
      of 1.7 +/- 0.4 nM) and on Swiss 3T3 cells (K(i) value of 1.0 +/- 0.2 nM). On the
      basis of this observation, antagonists containing the same dipeptide mimic were
      obtained by modification of the C-terminal part of the bombesin analogues. The
      most potent constrained compounds (15 and 17) were able to antagonize 1 nM
      bombesin-stimulated amylase secretion from rat pancreatic acini with high potency
      (K(i) = 21 +/- 3 and 3.3 +/- 1.0 nM, respectively) and 10(-7) M bombesin
      stimulated ?(3)Hthymidine incorporation into Swiss 3T3 cells (K(i) = 7.8 +/- 2. 0
      and 0.5 +/- 0.1 nM, respectively).

PMID- 10882362
TI  - Design, synthesis, and structure-activity relationships of novel non-imidazole
      histamine H(3) receptor antagonists.
AB  - Novel, potent, and selective non-imidazole histamine H(3) receptor antagonists
      have been prepared based on the low-affinity ligand dimaprit (pK(I) 7.32 +/-
      0.12, pK(B) 5.93 +/- 0.17). Detailed structure-activity studies have revealed
      that N-(4-chlorobenzyl)-N-(6-pyrrolidin-1-ylhexyl)guanidine (pK(I) 8.38 +/- 0.21,
      pK(B) 8.39 +/- 0.13), 30, and N-(4-chlorobenzyl)-N-(7-pyrrolidin-1
      ylheptyl)guanidine (pK(I) 8.78 +/- 0.12, pK(B) 8.38 +/- 0.10), 31, exhibit high
      affinity for the histamine H(3) receptor. Antagonists 30 and 31 demonstrate
      significant selectivity over the other histamine, H(1) and H(2), receptor
      subtypes and a 100-fold selectivity in the sigma(1) binding assay. Compounds
      30and 31 are the most potent, selective non-imidazole histamine H(3) receptor
      antagonists reported in the literature to date.

PMID- 10882363
TI  - Indeno[1,2-b]pyrazin-2,3-diones: a new class of antagonists at the glycine site
      of the NMDA receptor with potent in vivo activity.
AB  - Indeno?1,2-bpyrazin-2,3-diones have been identified as a novel series of potent
      ligands on the glycine site of the NMDA receptor. To improve their in vivo
      activities, an acetic acid-type side chain was introduced to the 5-position,
      giving water-soluble compounds when formulated as the sodium salt (>10 mg/mL).
      Introduction of a chlorine atom in the 8-position led to a dramatic improvement
      of anticonvulsant activity and this was surprising since this change did not
      improve binding affinity. A plausible explanation is a reduced recognition by a
      Na(+),K(+)-ATPase active transport system responsible for the excretion of these
      compounds from the brain and kidney. This promising new chemical series led to
      the optically active isomer (-)-10i (RPR 118723), a glycine/NMDA antagonist with
      nanomolar binding affinity and in vivo activity in animal model of convulsions
      and electrophysiology at doses in the range of 2-3 mg/kg following iv
      administration.

PMID- 10882364
TI  - Synthesis and biological evaluation of bradykinin B(1)/B(2) and selective B(1)
      receptor antagonists.
AB  - We recently described a potent bradykinin B(2) receptor agonist (JMV1116)
      obtained by replacing the D-Tic-Oic dipeptide moiety of HOE140 by a (3S)-amino-5
      (carbonylmethyl)-2,3-dihydro-1, 5-benzothiazepin-4(5H)-one (D-BT) moiety. This
      compound inhibited the specific binding of [(3)H]BK on membranes of CHO cells
      expressing the human cloned B(2) receptor with nanomolar affinity and contracted
      both isolated rat uterus and human umbilical vein. These data demonstrated that D
      BT could be a good mimic of the Pro-Phe dipeptide. In the present study we
      characterized B(1) receptor antagonists containing the D-BT moiety. We prepared
      an analogue of compound JMV1116 deleting the C-terminal arginine residue. The
      resulting compound (1) had an affinity of 83 nM for the human cloned B(1)
      receptor. The most remarkable property of 1 is its ability to bind also the B(2)
      receptor with an affinity of 4.4 nM despite the absence of the C-terminal
      arginine residue. Modifications at the N-terminal part of 1 associated with the
      substitution of the thienylalanine residue by alpha-(2-indanyl)glycine resulted
      in analogues selectively binding to the B(1) receptor with an affinity in the
      picomolar range.

PMID- 10882365
TI  - A rational approach to the design and synthesis of a new bradykinin B(1) receptor
      antagonist.
AB  - We have previously synthesized a potent and selective B(1) bradykinin receptor
      antagonist, JMV1645 (H-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-D-BT-OH), containing a
      dipeptide mimetic ((3S)-amino-5-carbonylmethyl-2,3-dihydro-1, 5-benzothiazepin
      4(5H)-one (D-BT) moiety) at the C-terminal. Analogues of this potent B(1)
      bradykinin receptor antagonist in which the central Pro(2)-Hyp(3)-Gly(4)-Igl(5)
      tetrapeptide has been replaced by constrained N-1-substituted-1,3,8
      triazaspiro?4. 5decan-4-one ring system were synthesized. Among these analogues,
      compound JMV1640 (1) was found to have an affinity of 24.10 +/- 9.48 nM for the
      human cloned B(1) receptor. It antagonized the ?des-Arg(10)-kallidin-induced
      contraction of the human umbilical vein (pA(2) = 6.1 +/- 0.1). Compound 1 was
      devoid of agonist activity at the kinin B(1) receptor. Moreover, it did not bind
      to the human cloned B(2) receptor. Therefore, JMV1640 constitutes a lead compound
      for the rational search of nonpeptide B(1) receptor analogues based on the BK
      sequence.

PMID- 10882366
TI  - Synthesis and cytotoxic and antitumor activity of benzo[b]pyrano[3, 2-h]acridin-7
      one analogues of acronycine.
AB  - Benzo?bacronycine (6-methoxy-3,3,14-trimethyl-3, 14-dihydro-7H-benzo?bpyrano?3,2
      hacridin-7-one, 4), an acronycine analogue with an additional aromatic ring
      linearly fused on the natural alkaloid basic skeleton, was synthesized in three
      steps, starting from 3-amino-2-naphthalenecarboxylic acid (5). Eight 1, 2
      dihydroxy-1,2-dihydrobenzo?bacronycine esters and diesters (17-24) were obtained
      by catalytic osmic oxidation, followed by acylation. All these compounds were
      significantly more cytotoxic than acronycine, when tested against L1210 leukemia
      cells in vitro. The potency of the cyclic carbonate 24 was in the range of the
      most active drugs currently used in cancer chemotherapy. Two selected diesters
      (17 and 24) were evaluated in vivo against P388 leukemia and colon 38
      adenocarcinoma implanted in mice. Both compounds were markedly active at doses 16
      fold lower than the dose of acronycine itself. Against colon 38 adenocarcinoma,
      compounds 17 and 24 were highly efficient, inhibiting tumor growth by more than
      80%. Diacetate 17 was the most active, inhibiting tumor growth by 96% at 6.25
      mg/kg, with two of seven mice being tumor-free on day 43.

PMID- 10882368
TI  - X-Ray structure of cytotoxic trans-[PtCl(2)(dimethylamine)(isopropylamine)]:
      interstrand cross-link efficiency, DNA sequence specificity, and inhibition of
      the B-Z transition.
AB  - We report here the X-ray structure of cytotoxic trans
      ?PtCl(2)(dimethylamine)(isopropylamine). This trans-platinum compound
      crystallizes in the monoclinic system, with Z = 8, in the spatial group C2/c with
      unit cell parameters a = 19.862(17) A, b = 6. 581(3) A, c = 18.563(3) A, alpha =
      90 degrees, beta = 119.16(3) degrees, gamma = 90 degrees, V = 2119(2) A(3), rho =
      2.321 Mg/m(3), R = 0.0505, and R(w) = 0.1166 on the basis of 2339 independent
      reflections. To our knowledge this is the first report of the crystal structure
      of a biologically active trans-platinum compound containing different aliphatic
      amines. The DNA binding mode of trans-?PtCl(2)(dimethylamine)(isopropylamine) may
      be a consequence of the spatial disposition of the dimethylamine and
      isopropylamine ligands around the trans-Pt(II) center. We have found that trans
      ?PtCl(2)(dimethylamine)(isopropylamine) readily forms DNA interstrand cross
      links. In addition, the compound shows binding affinity toward alternating purine
      pyrimidine sequences and inhibits the B-Z transition. These particular DNA
      binding properties might be related to the capacity of trans
      ?PtCl(2)(dimethylamine)(isopropylamine) for inducing some selective killing in a
      H-ras overexpresssing cell line.

PMID- 10882367
TI  - Water-soluble, core-modified porphyrins as novel, longer-wavelength-absorbing
      sensitizers for photodynamic therapy.
AB  - Water-soluble, core-modified 5,10,15, 20-tetrakis(4-sulfonatophenyl)-21,23
      dithiaporphyrin (1) and 5,10,15, 20-tetrakis(4-sulfonatophenyl)-21,23
      diselenaporphyrin (2) were prepared as the tetrasodium salts by the sulfonation
      of 5,10,15, 20-tetraphenyl-21,23-dithiaporphyrin (3) and -21, 23
      diselenaporphyrin (4), respectively, with sulfuric acid. Compounds 3 and 4 were
      prepared by the condensation of pyrrole with either 2,5
      bis(phenylhydroxymethyl)thiophene (5) or 2, 5-bis(phenylhydroxymethyl)selenophene
      (6) in propionic acid. The addition of benzaldehyde to 2,5-dilithiothiophene or
      2, 5-dilithioselenophene gives 5 or 6, respectively, as a nearly equimolar
      mixture of meso- and d,l-diastereomers. Careful crystallization of 5 gives a
      single diastereomer by removing the crystalline product from the equilibrating
      mixture of diastereomers in solution. Photodynamic therapy (PDT) with 1 has an
      LD(50) of less than 25 microg/mL against Colo-26 cells in culture and exhibits a
      lethal dose for 90% or more at concentrations greater than 50 microg/mL. In
      contrast, PDT with 5,10,15, 20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS(4))
      requires concentrations of greater than 100 microg/mL to achieve LD(50). Neither
      1 nor TPPS(4) shows significant photoactivity against the murine T-cell line,
      MOLT-4, above the dark toxicity. Sensitizer 1 shows no toxicity or side effects
      in BALB/c mice observed for 30 days following a single intravenous injection of
      10 mg (9.1 micromol)/kg. Distribution studies show that sensitizer 1 accumulates
      in the tumors of BALB/c mice bearing Colo-26 or EMT-6 tumors with sensitizer
      concentration roughly doubling as the dosage of 1 increased from 5 to 10 mg/kg.
      In vivo studies show that PDT with sensitizer 1 at both 3.25 and 10 mg/kg with
      135 J cm(-2) of 694-nm light is effective against Colo-26 tumors in BALB/c mice.

PMID- 10882369
TI  - Synthesis of B-ring homologated estradiol analogues that modulate tubulin
      polymerization and microtubule stability.
AB  - 2-Methoxyestradiol is a cytotoxic human metabolite of estradiol with the ability
      to bind to the colchicine site of tubulin and inhibit its polymerization, and its
      2-ethoxy analogue is even more potent. On the basis of a hypothetical
      relationship between the structures of colchicine and 2-methoxyestradiol, a B
      ring-expanded 2-ethoxyestradiol analogue was synthesized in which the B-ring of
      the steroid is replaced by the B-ring of colchicine. The synthesis relied on the
      B-ring expansion of available 6-keto estradiol derivatives as opposed to a total
      synthesis of the homologated steroid framework. The relative configurations of
      the acetamido substituents in both epimers of the final product were determined
      by NOESY NMR and confirmed by X-ray crystallography. The epimer having the 6alpha
      acetamido substituent was more active as an inhibitor of tubulin polymerization,
      and it was also more cytotoxic than the 6beta-epimer. These results are
      consistent with the proposed structural resemblance of 2-methoxyestradiol and
      colchicine. Several of the synthetic intermediates proved to be potent inhibitors
      of tubulin polymerization. On the other hand, a 3,17beta-diacetylated, B-ring
      expanded analogue of 2-ethoxyestradiol having a ketone at C-6 resembled
      paclitaxel (Taxol) in its ability to enhance tubulin polymerization and stabilize
      microtubules. The corresponding 3-acetate and the 17beta-acetate were both
      synthesized, and it was determined that the 17beta-acetate, but not the 3
      acetate, conferred on the steroid derivative its paclitaxel-like activity.

PMID- 10882370
TI  - Design, synthesis, and biological evaluation of tricyclic nucleosides
      (dimensional probes) as analogues of certain antiviral polyhalogenated
      benzimidazole ribonucleosides.
AB  - The polyhalogenated benzimidazole nucleosides 2,5, 6-trichloro-1-(beta-D
      ribofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were
      synthesized in our laboratory and established as potent and selective inhibitors
      of human cytomegalovirus (HCMV) with a novel mode of action. In an effort to
      study the behavior of the key substructure in a dimensionally extended manner and
      probe the spatial limitation of the target enzyme(s), a series of 2-substituted
      6, 7-dichloro-1-(beta-D-ribofuranosyl)naphtho?2,3-dimidazoles and the N1- and N3
      ribonucleosides of 2-substituted 6,7-dichloroimidazo?4, 5-bquinolines were
      prepared. The nucleosides 6, 7-dichloro-1-(beta-D-ribofuranosyl)imidazo?4,5
      bquinolin-2-one and 6,7-dichloro-3-(beta-D-ribofuranosyl)imidazo?4,5-bquinolin-2
      one were selected and used as the key synthetic intermediates in the imidazo?4,5
      bquinoline series. Evaluation of the compounds for activity against HCMV and
      herpes simplex virus type 1 revealed that the trichloro analogues of TCRB (2a,
      3a) were nearly as active against HCMV as TCRB but were more cytotoxic. The
      results suggest that extending the heterocycle of TCRB affected the affinity for
      the HCMV target only slightly but increased the affinity for cellular enzymes.

PMID- 10882371
TI  - Deoxy sugar analogues of triciribine: correlation of antiviral and
      antiproliferative activity with intracellular phosphorylation.
AB  - Triciribine (TCN) and triciribine monophosphate (TCN-P) have antiviral and
      antineoplastic activity at low micromolar or submicromolar concentrations. In an
      effort to improve and better understand this activity, we have conducted a
      structure-activity relationship study to explore requirements for the number of
      hydroxyl groups on the ribosyl moiety for biological activity. 2'
      Deoxytriciribine (2'-dTCN), 3'-deoxytriciribine (3'-dTCN), 2', 3'
      epoxytriciribine (2',3'-epoxyTCN), 2',3'-dideoxy-2', 3'-didehydrotriciribine
      (2',3'-d4TCN), and 2',3'-dideoxytriciribine (2',3'-ddTCN) were synthesized and
      evaluated for activity against human immunodeficiency virus (HIV-1), herpes
      simplex virus type 1 (HSV-1), and human cytomegalovirus (HCMV). Antiproliferative
      activity of the compounds also was tested in murine L1210 cells and three human
      tumor cell lines. All compounds were either less active than TCN and TCN-P or
      inactive at the highest concentration tested (100 microM) in both antiviral and
      antiproliferative assays. Reverse-phase HPLC of extracts from uninfected cells
      treated with the deoxytriciribine analogues only detected the conversion of 3'
      dTCN and 2',3'-ddTCN to their respective monophosphates. Therefore, either the
      deoxytriciribine analogues were not transported across the cell membrane or, more
      likely, they were not substrates for a nucleoside kinase or phosphotransferase.
      We have concluded that the hydroxyl groups on the ribosyl ring system of TCN and
      TCN-P must be intact in order to obtain significant antiviral and antineoplastic
      activity.

PMID- 10882372
TI  - Synthesis and antiviral evaluation of trisubstituted indole N-nucleosides as
      analogues of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB).
AB  - 2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6
      dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) are nucleosides that
      exhibit strong and selective activity against human cytomegalovirus (HCMV).
      Selected polyhalogenated indole nucleosides have now been synthesized as 3-deaza
      analogues of the benzimidazole nucleosides using the sodium salt glycosylation
      method. 2-Benzylthio-1-?2-deoxy-3, 5-bis-O-(4-methylbenzoyl)-beta-D-erythro
      pentofuranosyl-5, 6-dichloroindole (8) was prepared stereoselectively via the
      coupling of a 2-deoxyribofuranosyl alpha-chloride derivative with the sodium salt
      of 2-benzylthio-5,6-dichloroindole (5). Compound 8 was then elaborated into the
      targeted 2-benzylthio-1-(beta-D-ribofuranosyl)-5, 6-dichloroindole (18) in five
      steps. 2,5, 6-Trichloro-(1-beta-D-ribofuranosyl)indole (19) was prepared using
      the same synthetic route with 2,5,6-trichloroindole (6) as the starting material.
      We were subsequently able to prepare 19 in three steps using a modification of
      the sodium salt glycosylation method. 2-Bromo-5,6-dichloro-1-(beta-D
      ribofuranosyl)indole (25) was also prepared using the same procedures. Target
      compounds were tested for activity against HCMV, herpes simplex virus type 1 (HSV
      1), and human herpes virus six (HHV-6) and for cytotoxicity. All of the compounds
      were less active against HCMV than TCRB and weakly active or inactive against HSV
      1 and HHV-6.

PMID- 10882373
TI  - 6-N-Acyltriciribine analogues: structure-activity relationship between acyl
      carbon chain length and activity against HIV-1.
AB  - Triciribine (TCN) and triciribine-5'-monophosphate (TCN-P) are active against HIV
      1 at submicromolar concentrations. In an effort to improve and better understand
      this activity, we have conducted a structure-activity relationship study to
      explore the tolerance of TCN to structural modifications at the 6-position. A
      number of 6-N-acyltriciribine analogues were synthesized and evaluated for
      antiviral activity and cytotoxicity. The cytotoxicity of these compounds was
      minimal in three human cell lines (KB, CEM-SS cells, and human foreskin
      fibroblasts (HFF)). The compounds were marginally active or inactive against
      herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). In
      contrast, most of the compounds exhibited moderate to high activity against human
      immunodeficiency virus type 1 (HIV-1), IC(50)'s = 0.03 to 1 microM. This
      structure-activity relationship study identified the N-heptanoyl group as having
      the optimal carbon chain length. This compound was as active against HIV-1 as TCN
      and TCN-P. Reverse phase HPLC of extracts from uninfected cells treated with 6-N
      acyltriciribines detected sufficient TCN-P to account for anti-HIV activity
      thereby suggesting a prodrug effect. Studies in an adenosine kinase deficient
      cell line showed that the 6-N-acyl derivative was not phosphorylated directly but
      first was metabolized to triciribine which then was converted to TCN-P.

PMID- 10882374
TI  - Synthesis and antiviral evaluation of halogenated beta-D- and -L
      erythrofuranosylbenzimidazoles.
AB  - A series of 2-substituted benzimidazole D- and L-erythrofuranosyl nucleosides
      were synthesized and tested for activity against herpesviruses and for
      cytotoxicity. The D-nucleosides 2,5, 6-trichloro-1-(beta-D
      erythrofuranosyl)benzimidazole (8a) and 2-bromo-5,6-dichloro-1-(beta-D
      erythrofuranosyl)benzimidazole (8b) were prepared by coupling 1,2,3-tri-O-acetyl
      beta-D-erythrofuranose (D-6) with the appropriate benzimidazole, followed by
      removal of the acetyl protecting groups. The 2-isopropylamino (9), 2
      cyclopropylamino (10), and 2-mercaptobenzyl (11) derivatives were synthesized by
      nucleophilic displacements of the C-2 chlorine in the benzimidazole moiety of 8a.
      The D-nucleoside 4-bromo-5, 6-dichloro-2-isopropylamino-1-(beta-D
      erythrofuranosyl)benzimid azo le (17) was prepared by coupling D-6 with the
      appropriate benzimidazole. The L-erythrofuranosyl derivatives, 5, 6-dichloro-2
      isopropylamino-1-(beta-L-erythrofuranosyl)benzimid azo le (21a), its 2
      cyclopropylamino analogue (21b), and the 2-isopropylamino analogue (25), were
      prepared by coupling L-6 with the appropriate benzimidazole. Several of these new
      derivatives had very good activity against HCMV in plaque and yield reduction
      assays (IC(50) = 0.05-19 microM against the Towne strain of HCMV) and DNA
      hybridization assays. Very little activity was observed against other
      herpesviruses. This pattern is similar to the antiviral activity profile observed
      for the corresponding ribofuranosides 2,5, 6-trichloro-1-(beta-D
      ribofuranosyl)benzimidazole (4a), its 2-bromo analogue (4b), and the 2
      cyclopropylamino analogue (4c). In comparison, 8a was 15-fold more active against
      HCMV than 4a, and 8b was 4-fold more active against HCMV than 4b. The 5, 6
      dichloro-2-isopropylamino-1-(beta-L-erythrofuranosyl)benzimid azo le (21a) was
      less active than 4c, which is now in clinical trials for HCMV infection. Both
      8a,b had comparable HCMV activity to 4c. Mode of action studies with the D
      erythrose analogues established that 8b acted by inhibition of viral DNA
      processing whereas 9 and 10 may act via a different mechanism. The lack of a 5'
      hydroxymethyl group in all members of this series established that antiviral
      activity occurred without 5'-phosphorylation, a feature required for the activity
      of most nucleoside analogues.

PMID- 10882375
TI  - Synthesis of fluorosugar analogues of 2,5,6-trichloro-1-(beta-D
      ribofuranosyl)benzimidazole as antivirals with potentially increased glycosidic
      bond stability.
AB  - The metabolic instability in vivo of the glycosidic bond of 2,5, 6-trichloro-1
      (beta-D-ribofuranosyl)benzimidazole (TCRB) prompted us to design and synthesize
      the hitherto unreported fluorinated benzimidazole nucleosides 2,5, 6-trichloro-1
      (2-deoxy-2-fluoro-beta-D-arabinofuranosyl)benzimidazole , 2,5, 6-trichloro-1-(3
      deoxy-3-fluoro-beta-D-xylofuranosyl)benzimidazole, and 2-bromo-5, 6-dichloro-1-(2
      deoxy-2-fluoro-beta-D-ribofuranosyl)benzimidazole. TCRB was converted into the
      2',5'-ditrityl and 3',5'-ditrityl derivatives, which were fluorinated with DAST
      and deprotected to yield 2,5, 6-trichloro-1-(2-deoxy-2-fluoro-beta-D
      arabinofuranosyl)benzimidazole and 2,5, 6-trichloro-1-(3-deoxy-3-fluoro-beta-D
      xylofuranosyl)benzimidazole. The resulting low overall yield (5%) of 2,5, 6
      trichloro-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)benzimidazole encouraged us
      to develop an alternative route. The heterocycle 2,5, 6-trichlorobenzimidazole
      was condensed with 1-bromo-3, 5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D
      arabinofuranose to give, after deprotection, 2,5, 6-trichloro-1-(2-deoxy-2-fluoro
      beta-D-arabinofuranosyl)benzimidazole in a 50% overall yield. The 2'-deoxy-2'
      fluoro-beta-D-ribofuranosyl compounds were prepared using 2'-deoxy-2'
      fluorouridine, N-deoxyribofuranosyl transferase, and 5,6-dichlorobenzimidazole.
      Functionalization of the C2 position then gave the desired derivatives. Antiviral
      and cytotoxicity testing revealed that the deoxy fluoro arabinofuranosyl,
      xylofuranosyl, and ribofuranosyl derivatives were less active against human
      cytomegalovirus and more cytotoxic than TCRB.

PMID- 10882376
TI  - A potent aldose reductase inhibitor, (2S,4S)-6-fluoro-2', 5'-dioxospiro[chroman
      4,4'-imidazolidine]-2-carboxamide (Fidarestat): its absolute configuration and
      interactions with the aldose reductase by X-ray crystallography.
AB  - The absolute configuration of the aldose reductase (AR) inhibitor, (+)-(2S,4S)-6
      fluoro-2',5'-dioxospiro?chroman-4, 4'-imidazolidine-2-carboxamide (fidarestat),
      was established indirectly by single-crystal X-ray analysis of (+)-(2S, 4S)-8
      bromo-6-fluoro-2',5'-dioxospiro?chroman-4, 4'-imidazolidine-2-carboxylic acid
      (1). The crystal structure of human AR complexed with fidarestat was determined,
      and the specific inhibition activity was discussed on the basis of the three
      dimensional interactions between them. The structure clarified that fidarestat
      was located in the active site by hydrophilic and hydrophobic interactions and
      that the carbamoyl group of fidarestat was a very effective substituent for
      affinity to AR and for selectivity between AR and aldehyde reductase (AHR).
      Explanations for the differences between the observed activities of fidarestat
      and its stereoisomer 2 were suggested by computer modeling.

PMID- 10882377
TI  - Polyether mimics of naturally occurring cytotoxic annonaceous acetogenins.
AB  - On the basis of the ionophore model, polyether analogues 4 and 6 were designed
      and synthesized to mimic the naturally occurring annonaceous acetogenins
      corossolin (2) and bullatin (5), which were discovered as members of a large
      family of novel polyketides with cytotoxicity, antitumoral, and other biological
      activities since 1982. The preliminary screening shows that they have compatible
      cytotoxicity with the corresponding natural annonaceous acetogenins. These
      results open a potential way to find more active antitumor agents with simplified
      structures based on natural annonaceous acetogenins.

PMID- 10882378
TI  - Apoptosis in the vasculature: mechanisms and functional importance.
AB  - Apoptotic death has now been recognized in a number of common and threatening
      vascular diseases, including atherosclerosis. Interest in apoptosis research
      relates to the fact that apoptosis, in contrast to oncosis, is a highly regulated
      process of cell death which raises the hope for the development of specific
      therapeutic strategies to alter disease progression. This review summarizes the
      mechanisms involved in vascular endothelial and smooth muscle cell
      survival/apoptosis, and the potential roles of apoptotic death in atherosclerosis
      and restenosis. The potential effects of modulation of apoptosis in these
      diseases are also discussed.

PMID- 10882380
TI  - Leukaemia inhibitory factor (LIF) upregulates excitatory non-adrenergic non
      cholinergic and maintains cholinergic neural function in tracheal explants.
AB  - The effect of leukaemia inhibitory factor (LIF) in modulating cholinergic and
      sensory nerve function was examined using guinea-pig tracheal explants. Specific
      LIF receptors (LIFR) were immunolocalized to both cholinergic and sensory nerves.
      Release of SP in culture was not influenced by LIF. Similarly, maximum
      contraction to carbachol (C(max)) was not influenced by LIF. After 3 h, maximum
      (E(max)) eNANC-induced contraction in controls was 32+/-2. 5% of C(max). In LIF
      treated preparations, E(max) was enhanced to 50+/-4.5% C(max) (P<0.05).
      Cholinergic nerve-induced contractions after 3 h incubation with LIF were similar
      to control. After 24 h, control E(max) was 25+/-4.5% C(max) (58% smaller than
      E(max) at 3 h). In contrast, in LIF-treated preparations, E(max) was 37+/-2.5%
      C(max), (24% smaller than at 3 h, P<0.05). This did not appear to be due to the
      effect of LIF on muscarinic M(2) receptor expression or function. Thus LIF
      appears to differentially influence the function of airway nerves and thus may
      provide an important link between the immune and neural systems.

PMID- 10882379
TI  - Endothelial dysfunction in diabetes.
AB  - Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular
      disease. The endothelium controls the tone of the underlying vascular smooth
      muscle through the production of vasodilator mediators. The endothelium-derived
      relaxing factors (EDRF) comprise nitric oxide (NO), prostacyclin, and a still
      elusive endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium
      dependent vasodilation has been demonstrated in various vascular beds of
      different animal models of diabetes and in humans with type 1 and 2 diabetes.
      Several mechanisms of endothelial dysfunction have been reported, including
      impaired signal transduction or substrate availibility, impaired release of EDRF,
      increased destruction of EDRF, enhanced release of endothelium-derived
      constricting factors and decreased sensitivity of the vascular smooth muscle to
      EDRF. The principal mediators of hyperglycaemia-induced endothelial dysfunction
      may be activation of protein kinase C, increased activity of the polyol pathway,
      non-enzymatic glycation and oxidative stress. Correction of these pathways, as
      well as administration of ACE inhibitors and folate, has been shown to improve
      endothelium-dependent vasodilation in diabetes. Since the mechanisms of
      endothelial dysfunction appear to differ according to the diabetic model and the
      vascular bed under study, it is important to select clinically relevant models
      for future research of endothelial dysfunction.

PMID- 10882381
TI  - Role of loop D of the alpha7 nicotinic acetylcholine receptor in its interaction
      with the insecticide imidacloprid and related neonicotinoids.
AB  - 1. The nitroguanidine insecticide imidacloprid along with a second generation of
      related compounds including nitenpyram, all nicotinic acetylcholine (ACh)
      receptor ligands, are used increasingly in many countries. Site-directed
      mutagenesis and heterologous expression in Xenopus laevis oocytes have been
      deployed to investigate mutants (G189D and G189E) of the chicken alpha7 homomer
      forming nicotinic receptor subunit which are predicted to enhance the negative
      charge at the negative subsite (loop D) of the ACh binding site. 2. Xenopus
      oocytes expressing wild-type alpha7 nicotinic receptors respond to imidacloprid
      with rapid inward currents. Imidacloprid and nitenpyram are partial agonists,
      whereas ACh, (-)-nicotine and (+)-epibatidine are full agonists. 3. Compared to
      wild-type alpha7, the mutant G189D and G189E receptors are much less sensitive to
      the insecticides, whereas their sensitivity to (-)-nicotine, ACh and (+)
      epibatidine is only slightly reduced. In contrast, G189N and G189Q mutants are
      sensitive not only to ACh, (-)-nicotine and (+)-epibatidine, but also to the two
      insecticides. Thus reduction of the insecticide-sensitivity by the mutations
      G189D and G189E are attributed to an increase in negativity of loop D. Desnitro
      imidacloprid (DN-IMI), an imidacloprid derivative lacking the nitro group is a
      potent agonist on the G189D and G189E mutants suggesting an important role of
      loop D in nicotinic receptor interactions with the nitro group of nitroguanidine
      insecticides.

PMID- 10882382
TI  - Effects of sodium on agonist efficacy for G-protein activation in mu-opioid
      receptor-transfected CHO cells and rat thalamus.
AB  - 1. Sodium ions inhibit spontaneous G(i)/G(o)-coupled receptor activity and
      promote agonist-induced responses in vitro. The effects of sodium on the relative
      efficacy of opioid agonists for G-protein activation was measured by guanosine-5'
      O-(gamma-(35)S)-triphosphate ([(35)S]-GTPgammaS) binding in membranes from two mu
      opioid receptor-containing systems: CHO cells stably transfected with mouse
      mureceptors (mMOR-CHO cells) and rat thalamus. 2. NaCl inhibited basal [(35)S]
      GTPgammaS binding in both systems, and this effect was partially mimicked by KCl.
      In mMOR-CHO membranes, net [(35)S]-GTPgammaS binding stimulated by partial but
      not full agonists was inhibited by NaCl with a potency that was inversely
      proportional to agonist efficacy. Monovalent cations were required for agonist
      stimulated [(35)S]-GTPgammaS binding in this system, and increasing NaCl
      concentrations magnified relative efficacy differences among agonists. 3. In
      thalamic membranes, which contain a lower receptor:G-protein ratio than mMOR-CHO
      cells, similar monovalent cation effects were observed, with two exceptions: (1)
      [(35)S]-GTPgammaS binding stimulated by both full and partial agonists was
      inhibited by NaCl; and (2) monovalent cations were not required to observe
      agonist-stimulated [(35)S]-GTPgammaS binding. 4. Basal [(35)S]-GTPgammaS binding
      stimulated by the absence of monovalent cations resembled that of agonist
      stimulated binding and was blocked by pretreatment of mMOR-CHO cells with
      pertussis toxin. 5. These results indicate that sodium inhibits spontaneous and
      agonist-occupied mu receptor-mediated G-protein activation in a manner inversely
      proportional to the efficacy of the agonist, and that spontaneous mu receptor
      activity and the relative efficacy of partial agonists acting at these receptors
      are both increased by increases in the stoichiometric ratio of receptors:G
      proteins.

PMID- 10882383
TI  - Critical dependence of the NO-mediated component of cyclic AMP-induced
      vasorelaxation on extracellular L-arginine in pulmonary arteries of the rat.
AB  - A component of isoprenaline-mediated vasorelaxation in pulmonary arteries is
      mediated by nitric oxide (NO). We examined the effects of physiological
      concentrations (</=400 microM) of L-arginine on isoprenaline-induced relaxation
      in rat pulmonary arteries, and following inhibition of L-arginine uptake with L
      lysine. In addition, we examined the role of the endothelium, and whether L
      arginine affected acetylcholine (ACh)-induced relaxation. Isoprenaline-induced
      relaxation was potentiated by 400 microM L-arginine in pulmonary arteries;
      maximum relaxation was increased from 83+/-4% of initial tone to 94+/-4%
      (P<0.05). L-lysine (10 mM) not only abolished the potentiation by L-arginine, but
      suppressed relaxation compared to control (70+/-4%, P<0.05), even in the absence
      of L-arginine added to the bath. Blockade of NO synthase with 100 microM L-NMMA
      or removal of the endothelium inhibited isoprenaline-induced relaxation to the
      same extent as L-lysine, and under these conditions the presence or absence of
      400 microM L-arginine made no difference. L-lysine had no additional effect when
      applied in combination with L-NMMA. The effect of extracellular L-arginine was
      concentration dependent, with an apparent EC(50) of approximately 1-7 microM.
      Relaxation to the membrane permeant cyclic AMP analogue CPT cyclic AMP was also
      potentiated by L-arginine and inhibited by L-lysine. There was however no
      difference in relaxation induced by acetylcholine (ACh) in the presence of L
      arginine or L-lysine, and isoprenaline-induced relaxation of mesenteric arteries
      was unaffected by L-arginine or L-lysine. These results strongly suggest that
      extracellular L-arginine is critically important for development of the NO- and
      endothelium-dependent component of cyclic AMP-induced vasorelaxation in rat
      pulmonary arteries, but is not required for ACh-induced relaxation. As the
      apparent EC(50) for this effect is in the low micromolar range it is likely to be
      fully activated in vivo, as plasma L-arginine is >150 microM.

PMID- 10882384
TI  - Blockade of phencyclidine-induced effects by a nitric oxide donor.
AB  - 1. Phencyclidine (PCP) is widely used as an animal model of schizophrenia. The
      aim of this study was to better understand the role of nitric oxide (NO) in the
      mechanism of action of PCP and to determine whether positive NO modulators may
      provide a new approach to the treatment of schizophrenia. 2. The effects of the
      NO donor, sodium nitroprusside (SNP), were studied in PCP-treated rats. Following
      drug administration, behavioural changes and the expression of c-fos, a metabolic
      marker of functional pathways in the brain, were simultaneously monitored. 3.
      Acute PCP (5 mg kg(-1), i. p.) treatment induced a complex behavioural syndrome,
      consisting of hyperlocomotion, stereotyped behaviours and ataxia. Treatment with
      SNP (2 - 6 mg kg(-1), i.p.) by itself produced no effect on any behaviour studied
      but completely abolished PCP-induced behaviour in a dose- and time-dependent
      manner. 4. PCP had differential regional effects on c-fos expression in rat
      brain, suggesting regionally different patterns of neuronal activity. The most
      prominent immunostaining was observed in the cortical regions. Pre-treatment with
      SNP blocked PCP-induced c-fos expression at doses similar to those that suppress
      PCP-induced behavioural effects. 5. These results implicate the NO system in the
      mechanism of action of PCP. The fact that SNP abolished effects of PCP suggests
      that drugs targeting the glutamate-NO system may represent a novel approach to
      the treatment of PCP-induced psychosis and schizophrenia.

PMID- 10882385
TI  - Cholinergic facilitation of neurotransmission to the smooth muscle of the guinea
      pig prostate gland.
AB  - 1. Functional experiments have been conducted to assess the effects of
      acetylcholine and carbachol, and the receptors on which they act to facilitate
      neurotransmission to the stromal smooth muscle of the prostate gland of the
      guinea-pig. 2. Acetylcholine and carbachol (0.1 microM - 0.1 mM) enhanced
      contractions evoked by trains of electrical field stimulation (20 pulses of 0.5
      ms at 10 Hz every 50 s with a dial setting of 60 V) of nerve terminals within the
      guinea-pig isolated prostate. In these concentrations they had negligible effects
      on prostatic smooth muscle tone. 3. The facilitatory effects of acetylcholine,
      but not those of carbachol, were further enhanced in the presence of
      physostigmine (10 microM). 3. The facilitatory effects of carbachol were
      unaffected by the neuropeptide Y Y(1) receptor antagonist BIBP 3226 ((R)-N(2)
      (diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-arginina mide) (0.3 microM, n=3) or
      suramin (100 microM, n=5). Prazosin (0.1 microM, n=5) and guanethidine (10
      microM, n=5) alone and in combination (n=4), reduced responses to field
      stimulation and produced rightward shifts of the log concentration-response
      curves to carbachol. 4. The rank orders of potency of subtype-preferring
      muscarinic receptor antagonists in inhibiting the facilitatory actions of
      acetylcholine and carbachol were: pirenzepine > HHSiD (hexahydrosiladifenidol) >
      pF-HHSiD (para-fluoro-hexahydrosiladifenidol)>/= 5 himbacine, and pirenzepine >
      HHSiD > himbacine>/= 5 pF-HHSiD, respectively. These profiles suggest that
      muscarinic receptors of the M(1)-subtype mediate the facilitatory effects of
      acetylcholine and carbachol on neurotransmission to the smooth muscle of the
      guinea-pig prostate.

PMID- 10882386
TI  - Characteristics of the Ca(2+)-dependent inhibition of cyclic AMP accumulation by
      histamine and thapsigargin in human U373 MG astrocytoma cells.
AB  - 1. Histamine, acting on H(1)-receptors, caused a Ca(2+)-dependent inhibition of
      forskolin- and isoprenaline-induced cyclic AMP accumulation in monolayers of
      human U373 MG cells (IC(50) 1.3+/-0.3 microM, maximum inhibition 66+/-3%). The
      inhibition was not reversed by the protein kinase inhibitor K-252A. 2.
      Thapsigargin also inhibited cyclic AMP accumulation (IC(50) 6.0+/-0.3 nM, maximum
      inhibition 72+/-1%). In the absence of extracellular Ca(2+) 5 microM thapsigargin
      caused only a 12+/-2% inhibition of cyclic AMP accumulation. 3. The inhibitory
      effect of 100 nM thapsigargin on forskolin-stimulated cyclic AMP accumulation was
      blocked by La(3+) (best-fit maximum inhibition 81+/-4%, IC(50) 125+/-8 nM). In
      contrast, the inhibitory action of 10 microM histamine was much less sensitive to
      reversal by 1 microM La(3+) (33+/-5% reversal, compared with 78+/-6% reversal of
      the inhibition by thapsigargin measured concurrently). However, in the presence
      of both thapsigargin and histamine the inhibition of cyclic AMP accumulation was
      reversed by 1 microM La(3+) to the same extent as the inhibition by thapsigargin
      alone. 4.++Thapsigargin (5 microM)+1 microM La(3+) caused only a 20+/-1%
      inhibition of histamine-stimulated phosphoinositide hydrolysis. 5. There was no
      indication from measurement of intracellular Ca(2+) of any persistent La(3+)
      insensitive Ca(2+) entry component activated by histamine. 6. The results provide
      evidence that Ca(2+) entry is required for the inhibition by histamine and
      thapsigargin of drug-induced cyclic AMP accumulation in U373 MG astrocytoma
      cells. The differential sensitivity of the inhibitory action of the two agents to
      block by La(3+) suggests that more than one pathway of Ca(2+) entry is involved.

PMID- 10882387
TI  - The inhibition of cholera toxin-induced 5-HT release by the 5-HT(3) receptor
      antagonist, granisetron, in the rat.
AB  - 1. The secretagogue 5-hydroxytryptamine (5-HT) is implicated in the
      pathophysiology of cholera. 5-HT released from enterochromaffin cells after
      cholera toxin exposure is thought to activate non-neuronally (5-HT(2) dependent)
      and neuronally (5-HT(3) dependent) mediated water and electrolyte secretion. CT
      secretion can be reduced by preventing the release of 5-HT. Enterochromaffin
      cells possess numerous receptors that, under basal conditions, modulate 5-HT
      release. 2. These include basolateral 5-HT(3) receptors, the activation of which
      is known to enhance 5-HT release. 3. Until now, 5-HT(3) receptor antagonists
      (e.g. granisetron) have been thought to inhibit cholera toxin-induced fluid
      secretion by blockading 5-HT(3) receptors on secretory enteric neurones. Instead
      we postulated that they act by inhibiting cholera toxin-induced enterochromaffin
      cell degranulation. 4. Isolated intestinal segments in anaesthetized male Wistar
      rats, pre-treated with granisetron 75 microg kg(-1), lidoocaine 6 mg kg(-1) or
      saline, were instilled with a supramaximal dose of cholera toxin or saline. Net
      fluid movement was determined by small intestinal perfusion or gravimetry and
      small intestinal and luminal fluid 5-HT levels were determined by HPLC with
      fluorimetric detection. 5. Intraluminal 5-HT release was proportional to the
      reduction in tissue 5-HT levels and to the onset of water and electrolyte
      secretion, suggesting that luminal 5-HT levels reflect enterochromaffin cell
      activity. 6. Both lidocaine and granisetron inhibited fluid secretion. However,
      granisetron alone, and proportionately, reduced 5-HT release. 7. The simultaneous
      inhibition of 5-HT release and fluid secretion by granisetron suggests that 5-HT
      release from enterochromaffin cells is potentiated by endogenous 5-HT(3)
      receptors. The accentuated 5-HT release promotes cholera toxin-induced fluid
      secretion.

PMID- 10882388
TI  - Effect of amygdala kindling on the central nervous system effects of tiagabine:
      EEG effects versus brain GABA levels.
AB  - 1. The objective of this investigation was to determine the influence of amygdala
      kindling on the pharmacodynamics of tiagabine in vivo, using quantitative EEG
      parameters and extracellular GABA concentrations as pharmacodynamic endpoints. In
      integrated pharmacokinetic/pharmacodynamic (PK/PD) studies the time course of
      these effects was determined in conjunction with plasma concentrations following
      intravenous administration of 10 mg kg(-1). An 'effect compartment' model was
      used to derive individual concentration - effect relationships. 2. ++Tiagabine
      produced an increase in the amplitude of the 11.5 - 30 Hz frequency band of the
      EEG. The relationship between concentration and EEG effect was non-linear and
      described by the Hill equation. 3. In kindled rats the EC(50) was reduced to 291
      ng ml(-1) from the original value of 521 ng ml(-1) in controls. The values of all
      other parameters were unchanged. In kindled rats the baseline extracellular GABA
      concentration was increased to 1.58 microM from 0.74 microM in controls. The
      relationships between tiagabine concentration and extracellular GABA
      concentration were again non-linear and described by the Hill equation. No
      differences were observed between kindled rats and controls. In the
      synaptoneurosmal preparation in vitro no changes in the functioning of the GABA
      transporter were observed. 4. It is concluded that unlike the situation with
      midazolam, there is no resistance to the EEG effect of tiagabine in the kindling
      model of experimental epilepsy. The observed shift in the concentration - EEG
      effect relationship to lower concentrations can presumably be explained by the
      increase in the baseline GABA levels.

PMID- 10882389
TI  - Regulation of human D(1), d(2(long)), d(2(short)), D(3) and D(4) dopamine
      receptors by amiloride and amiloride analogues.
AB  - 1. The modulatory effects of the allosteric effectors methylisobutylamiloride
      (MIA), benzamil and amiloride have been examined at human D(1), D(2), D(3) and
      D(4) dopamine receptors. The subtype selectivity and the mechanism of action of
      this allosteric regulation was examined. 2. In radioligand dissociation
      experiments each modulator accelerated dissociation from all four receptor
      subtypes indicating allosteric regulation. MIA displayed selectivity for the D(3)
      subtype for acceleration of radioligand dissociation. 3. In equilibrium binding
      (pseudo-competition) experiments the three compounds inhibited radioligand
      binding at the four receptor subtypes. Inhibition curves for D(1), D(2(short)),
      D(2(long)) and D(3) receptors were described by Hill coefficients exceeding unity
      and data were fitted best by a model that assumes binding of modulator to both
      the primary and allosteric binding sites of the receptor (the
      allosteric/competitive model). 4. At the D(4) subtype, Hill coefficients of unity
      described the binding data for amiloride and benzamil, consistent with
      competitive inhibition. The Hill coefficient for MIA at the D(4) subtype was less
      than unity and data could be fitted well by the allosteric/competitive model, but
      it was not possible to define unambiguously the modulatory mechanism. For this
      effect a better definition of the mechanism could be obtained by simultaneous
      analysis of data obtained in the presence of a range of concentrations of a
      purely competitive ligand. 5. MIA reduced the potency with which dopamine
      stimulated [(35)S]-GTPgammaS binding at the D(2) receptor. The effects of MIA
      could be described by the allosteric/competitive model with effects of MIA to
      inhibit the binding of dopamine but not its ability to induce a response.

PMID- 10882390
TI  - Nitric oxide mediated modulation of norepinephrine transport: identification of a
      potential target for S-nitrosylation.
AB  - 1. Carrier mediated uptake (uptake-1) transport of norepinephrine (NE) plays a
      key role in the regulation of sympathetic neurotransmission. Recent
      investigations indicate that nitric oxide (NO) may modulate uptake-1 activity,
      possibly in a cyclic GMP independent manner. 2. Carrier mediated transport of
      [(3)H-NE] and [(3)H-dopamine, DA] was examined in CHO cells transfected with cDNA
      for the NE and DA transporters (NET, DAT) respectively. 3. While exposure to the
      NO donor S-nitroso-N-acetylpenicillamine (100 microM, SNAP) significantly reduced
      [(3)H-NE] uptake (P<0.001), no effect on [(3)H-DA] transport was apparent. 4.
      Comparison of the amino acid sequences for NET and DAT identified cysteine
      residue 351 in NET, which was not present in DAT. Site-directed mutagenesis of
      Cys 351 to Ser produced a functional NET that was resistant to the inhibitory
      effects of SNAP. 5. The presence of SNAP mediated nitrosylation of the cysteine
      residue in an 8-mer model peptide based around Cys 351 in NET was confirmed by
      both biochemical and mass spectroscopic means. 6. These data indicate the
      potential regulatory role for NO in modulating sympathetic neurotransmission, and
      further confirm the importance of non-cyclic GMP dependent mechanisms in
      mediating the actions of NO.

PMID- 10882391
TI  - Role of A(2A)-adenosine receptor activation for ATP-mediated coronary
      vasodilation in guinea-pig isolated heart.
AB  - 1. Adenosine-5'-triphosphate (ATP) and adenosine are potent coronary
      vasodilators. ATP is rapidly converted to adenosine by ectonucleotidases. We
      examined whether coronary vasodilation caused by exogenous ATP is mediated by
      P(2) receptor activation or by A(2A)-adenosine receptor activation. 2. Effects of
      interventions on coronary conductance were determined by measuring coronary
      perfusion pressure in guinea-pig isolated hearts perfused at a constant flow of
      10 ml min(-1). 3. ATP and adenosine both caused sustained, concentration
      dependent increases of coronary conductance. Maximal responses to both agonists
      were equivalent. The values of pD(2) (+/-s.e.mean) for ATP and adenosine were
      6.68+/-0.04 and 7.06+/-0.05, respectively. Adenosine was significantly more
      potent than ATP (P<0. 0001, n=10). 4. The values of pIC(50) for the selective
      A(2A)-adenosine receptor antagonist SCH58261 to antagonize equivalent responses
      to ATP and adenosine were 8.28+/-0.08 and 8.28+/-0.06 (P=0.99, n=6),
      respectively. 5. The non-selective adenosine receptor antagonists xanthine amine
      congener (XAC) and CGS15943 antagonized similarly the equivalent vasodilations
      caused by ATP (pIC(50) values 7.48+/-0.04 and 7.45+/-0.06, respectively) and
      adenosine (pIC(50) values 7. 37+/-0.13 and 7.56+/-0.11). 6. In contrast to ATP
      and adenosine, the two P(2) agonists 2-methylthio-ATP and uridine-5'-triphosphate
      failed to cause stable increases of coronary conductance, caused desensitization
      of vasodilator responses, and were not antagonized by SCH 58261, 8
      parasulphophenyltheophylline, or XAC. 7. Glibenclamide attenuated coronary
      vasodilations caused by ATP and adenosine by 88 and 89%, respectively, but failed
      to attenuate those caused by 2-methylthio-ATP. 8. These results strongly suggest
      that sustained, submaximal coronary vasodilation caused by exogenous ATP is
      entirely mediated by adenosine acting upon A(2A)-adenosine receptors.

PMID- 10882392
TI  - Participation of kinins in the captopril-induced inhibition of intimal
      hyperplasia caused by interruption of carotid blood flow in the mouse.
AB  - 1. In the rat balloon injury model, angiotensin-converting enzyme (ACE)
      inhibitors prevent vascular remodelling by inhibiting angiotensin II generation
      and kinin breakdown. We investigated if ACE inhibition also prevents the
      structural vascular responses to disruption of carotid artery blood flow and if
      kinin potentiation plays a role in such a protection. 2. Morphometric analysis of
      the structural alterations caused by ligation of the left carotid artery was
      performed 14 days after surgery in J129Sv wild-type mice (B(2)(+/+)) drinking
      normal tap water or water containing captopril (120 mg kg(-1) per day). In
      addition, the effect of captopril on vascular remodelling was tested in B(2)(+/+)
      given the bradykinin (BK) B(1) receptor antagonist des-Arg(9)-[Leu(8)]-BK (DALBK,
      50 nmol kg(-1) per day, intraperitoneally) or the BK B(2) receptor antagonist D
      Arg, [Hyp(3),Thi(5)D-Tic(7),Oic(8)]-BK (icatibant, 1 micromol kg(-1) per day,
      intraperitoneally), and in B(2) receptor gene knockout mice (B(2)(-/-)). 3.
      Interruption of blood flow resulted in carotid artery intimal hyperplasia and
      media thickening in untreated B(2)(+/+), these responses being partially
      suppressed by captopril. The inhibition of intimal thickening exerted by
      captopril was reduced in B(2)(+/+) given DALBK or icatibant (P<0.05 for both
      comparisons) as well as in B(2)(-/-) (P<0.05). Neither antagonism of kinin
      receptors nor disruption of the B(2) receptor gene altered the suppressive effect
      of captopril on media thickening. The protection of vascular wall structure was
      independent of the reduction in blood pressure by captopril. 4. These results
      demonstrate that kinins participate in the inhibitory effect of captopril on
      intimal hyperplasia via B(1) and B(2) receptor signalling. Our findings may have
      important implications in treating vascular remodelling evoked by altered shear
      stress conditions.

PMID- 10882393
TI  - Endogenous calcitonin gene-related peptide (CGRP) mediates adrenergic-dependent
      vasodilation induced by nicotine in mesenteric resistance arteries of the rat.
AB  - 1. The mechanisms underlying vasodilator effect of nicotine on mesenteric
      resistance blood vessels and the role of calcitonin gene-related peptide (CGRP)
      containing (CGRPergic) vasodilator nerves were studied in the rat. 2. Mesenteric
      vascular beds isolated from Wistar rats were perfused with Krebs solution, and
      perfusion pressure was measured with a pressure transducer. 3. In preparations
      with intact endothelium and contracted by perfusion with Krebs solution
      containing methoxamine, perfusion of nicotine (1 - 100 microM) for 1 min caused a
      concentration-dependent vasodilator response without vasoconstriction. 4. The
      nicotine-induced vasodilation was markedly inhibited by hexamethonium (nicotinic
      cholinoceptor antagonist, 10 microM) and blocked by guanethidine (adrenergic
      neuron blocker, 5 microM). 5. Either denervation by cold storage (4 degrees C for
      72 h) or adrenergic denervation by 6-hydroxydopamine (toxin for adrenergic
      neurons, 2 mM for 20 min incubation, twice) blocked the nicotine-induced
      vasodilation. 6. Neither endothelium removal with perfusion of sodium
      deoxycholate (1.80 mg ml(-1), for 30 s) nor treatment with N(omega)-nitro-L
      arginine (nitric oxide synthase inhibitor, 100 microM), atropine (muscarinic
      cholinoceptor antagonist, 10 nM) or propranolol (beta-adrenoceptor antagonist,
      100 nM) affected the nicotine-induced vasodilation. 7. In preparations without
      endothelium, treatment with capsaicin (depleting CGRP-containing sensory nerves,
      1 microM) or human CGRP[8 - 37] (CGRP receptor antagonist, 0.5 microM) markedly
      inhibited the nicotine-induced vasodilation. 8. These results suggest that, in
      the mesenteric resistanc artery of the rat, nicotine induces vasodilation, which
      is independent of the function of the endothelium and is involved in activation
      of CGRPergic nerves. It is also suggested that nicotine stimulates presynaptic
      nicotinic cholinoceptors on adrenergic nerves to release adrenergic
      neurotransmitters, which then act on CGRPergic nerves to release endogenous CGRP
      from the nerve.

PMID- 10882394
TI  - Deoxycorticosterone acetate-salt hypertensive rats display gender-related
      differences in ET(B) receptor-mediated vascular responses.
AB  - 1. Male DOCA-salt rats exhibit vasoconstriction upon ET(B) activation. Because
      hypertension is less severe in female than male DOCA rats, we hypothesized that
      female DOCA rats would display attenuated ET(B) vasoconstrictor responses. 2.
      Uninephrectomized Wistar rats received DOCA and drinking water containing
      NaCl/KCl. Control rats received vehicle and tap water. Systolic blood pressure
      was higher in male vs female DOCA rats. Responses to endothelin-1 (ET-1), IRL
      1620, an ET(B) agonist, and acetylcholine were evaluated in isolated aortas and
      in vivo in the mesenteric microcirculation. 3. Endothelium-denuded aortas from
      male, but not female, DOCA rats displayed increased sensitivity to ET-1. IRL-1620
      contracted aortas from male DOCA rats, but not control or female DOCA aortas.
      Noradrenaline-constricted and endothelium-intact aortas from male, but not
      female, DOCA rats displayed increased relaxation to IRL-1620 compared to control
      aortas. 4. In vivo, increased vasoconstriction to ET-1 was observed in male and
      female DOCA rats. IRL-1620 induced vasodilation in control rats, but
      vasoconstriction in male DOCA rats. There were minimal changes in diameter in
      vessels from female DOCA rats. 5. The initial fall in blood pressure induced by
      ET-1 and IRL-1620 was attenuated in male DOCA rats. Bosentan, a mixed ET(A)/ET(B)
      receptor antagonist, lowered blood pressure in male and female DOCA rats, but a
      greater and marked decrease occurred in the male DOCA group. 6. The gender
      related differences in ET-1/ET(B)-mediated effects both in the vasculature and
      blood pressure suggest that sex-related functional up-regulation of ET(B)
      receptors may play a role in the more severe hypertension in male DOCA
      hypertensive rats.

PMID- 10882396
TI  - 5-HT(1A) receptor agonist-antagonist binding affinity difference as a measure of
      intrinsic activity in recombinant and native tissue systems.
AB  - 1. It has been reported that radiolabelled agonist : antagonist binding affinity
      ratios can predict functional efficacy at several different receptors. This study
      investigates whether this prediction is true for recombinant and native tissue 5
      HT(1A) receptors. 2. Saturation studies using [(3)H]-8-OH-DPAT and [(3)H]-MPPF
      revealed a single, high affinity site (K(D)approximately 1 nM) in HEK293 cells
      expressing human 5-HT(1A) receptors and rat cortex. In recombinant cells, [(3)H]
      MPPF labelled 3 - 4 fold more sites than [(3)H]-8-OH-DPAT suggesting the presence
      of more than one affinity state of the receptor. [(3)H]-Spiperone labelled a
      single, lower affinity site in HEK293 cells expressing h5-HT(1A) receptors but
      did not bind to native tissue 5-HT(1A) receptors. These data suggest that, in
      transfected HEK293 cells, human 5-HT(1A) receptors exist in different affinity
      states but in native rat cortical tissue the majority of receptors appear to
      exist in the high agonist affinity state. 3. Receptor agonists inhibited [(3)H]
      MPPF binding from recombinant 5-HT(1A) receptors in a biphasic manner, whereas
      antagonists and partial agonists gave monophasic inhibition curves. All compounds
      displaced [(3)H]-8-OH-DPAT and [(3)H]-spiperone binding in a monophasic manner.
      In rat cortex, all compounds displaced [(3)H]-MPPF and [(3)H]-8-OH-DPAT in a
      monophasic manner. 4. Functional evaluation of compounds, using [(35)S]-GTPgammaS
      binding, produced a range of intrinsic activities from full agonism, displayed by
      5-HT and 5-CT to inverse agonism displayed by spiperone. 5. [(3)H]-8-OH-DPAT :
      [(3)H]-MPPF pK(i) difference correlated well with functional intrinsic activity
      (r=0.86) as did [(3)H]-8-OH-DPAT : [(3)H]-spiperone pK(i) difference with
      functional intrinsic activity (r=0.96). 6. Thus agonist : antagonist binding
      affinity differences may be used to predict functional efficacy at human 5-HT(1A)
      receptors expressed in HEK293 cells where both high and low agonist affinity
      states are present but not at native rat cortical 5-HT(1A) receptors in which
      only the high agonist affinity state was detectable.

PMID- 10882395
TI  - Evidence for activation of the tissue kallikrein-kinin system in nociceptive
      transmission and inflammatory responses of mice using a specific enzyme
      inhibitor.
AB  - The pharmacological activity of phenylacetyl-Phe-Ser-Arg-N-(2, 4-dinitrophenyl)
      ethylenediamine (TKI), a tissue kallikrein specific inhibitor, was assessed using
      models of nociception and inflammation in mice. Injection of TKI (13.6 - 136
      micromol kg(-1), i.p. or 41 - 410 micromol kg(-1), s.c.) produced a dose-related
      inhibition of the acetic acid-induced writhes (by 37 to 85% or 34 to 80%,
      respectively). The antinociceptive activity of TKI (41 micromol kg(-1), i.p.) was
      maximal after 30 min injection and lasted for 120 min. The effect was unaltered
      by pretreatment with naloxone (8.2 micromol kg(-1), s.c.) or bilateral
      adrenalectomy. TKI (41 and 136 micromol kg(-1), i.p.) produced a dose-related
      decrease of the late phase of formalin-induced nociception by 79 and 98%,
      respectively. At 136 micromol kg(-1), i.p., TKI also shortened the duration of
      paw licking in the early phase by 69%. TKI (41 and 136 micromol kg(-1), i.p.)
      also reduced the capsaicin-induced nociceptive response (by 51 to 79%). TKI (41
      micromol kg(-1), i.p. or 410 micromol kg(-1), s.c.) reduced the oedematogenic
      response, from the second to the fifth hour after carrageenin injection by 36 to
      30% or by 47 to 39%, respectively. Pretreatment with TKI (41 micromol kg(-1),
      i.p.) reduced the capsaicin-induced neurogenic inflammation in the mouse ear by
      54%. It is concluded that TKI presents antinociceptive and antiinflammatory
      activities mediated by inhibition of kinin formation by tissue kallikrein in
      mice. The results also indicate that the tissue kallikrein-dependent pathway
      contributes to kinin generation in nociceptive and inflammatory processes in
      mice.

PMID- 10882397
TI  - Inhibition of mitochondrial proton F0F1-ATPase/ATP synthase by polyphenolic
      phytochemicals.
AB  - Mitochondrial proton F0F1-ATPase/ATP synthase synthesizes ATP during oxidative
      phosphorylation. In this study, we examined the effects of several groups of
      polyphenolic phytochemicals on the activity of the enzyme. Resveratrol, a
      stilbene phytoalexin that is present in grapes and red wine, concentration
      dependently inhibited the enzymatic activity of both rat brain and liver F0F1
      ATPase/ATP synthase (IC(50) of 12 - 28 microM). Screening of other polyphenolic
      phytochemicals using rat brain F0F1-ATPase activity resulted in the following
      ranking potency (IC(50) in parenthesis): piceatannol (8 microM)>resveratrol (19
      microM)=(-)epigallocatechin gallate (17 microM)>(-)epicatechin gallate, curcumin
      (45 microM)>genistein=biochanin A=quercetin=kaempferol=morin (55 - 65
      microM)>phloretin=apigenin=daidzein (approx. 100 microM). Genistin, quercitrin,
      phloridzin, (+)catechin, (+)epicatechin, (-)epicatechin and (-)epigallocatechin
      had little effect at similar concentrations. Tannic acid, theaflavins (tea
      extract) and grape seed proanthocyanidin extract (GSPE) had IC(50) values of 5,
      20 and 30 microg ml(-1), respectively. Several monophenolic antioxidants and non
      phenolic compounds were ineffective at concentrations of 210 microM or higher.
      The inhibition of F0F1-ATPase by resveratrol and genistein was non-competitive in
      nature. The effects of polyphenolic phytochemicals were additive. Both
      resveratrol and genistein had little effect on the Na(+)/K(+)-ATPase activity of
      porcine cerebral cortex, whereas quercetin had similar inhibitory potency as for
      F0F1-ATPase. In conclusion, the ATP synthase is a target for dietary
      phytochemicals. This pharmacological property of these phytochemicals should be
      included in the examination of their health benefits as well as potential
      cytotoxicity.

PMID- 10882398
TI  - On the regulation of ischaemia-induced glutamate efflux from rat cortex by GABA;
      in vitro studies with GABA, clomethiazole and pentobarbitone.
AB  - Prisms of adult rat cortex were maintained in vitro in either aerobic conditions
      (control) or conditions simulating an acute ischaemic challenge (hypoxia with no
      added glucose). Endogenous glutamate efflux increased with time in ischaemic
      conditions, being 2.7 fold higher than control efflux at 45 min. Returning prisms
      to control solution after 20 min of simulated ischaemia resulted in glutamate
      efflux returning to near-control values. Endogenous GABA efflux in ischaemic
      conditions also increased, being 4.5 fold higher than control efflux at 45 min.
      Ischaemia-induced glutamate efflux was not accompanied by increased lactate
      dehydrogenase efflux and was unaltered by omitting calcium from the extra
      cellular solution and adding EGTA (0.1 mM). Both GABA and the GABA-mimetic
      clomethiazole inhibited ischaemia-induced glutamate efflux, with IC(50) values of
      26 and 24 microM respectively. The maximum inhibition by either drug was 60 -
      70%. Bicuculline (10 microM) abolished the inhibitory effect of GABA (100 microM)
      but not clomethiazole (100 microM). Picrotoxin (100 microM) abolished the action
      of both GABA and clomethiazole. Pentobarbitone inhibited glutamate efflux at 100 
      300 microM (maximal inhibition: 39%). Bicuculline (10 microM) abolished this
      effect. These data suggest that ischaemia-induced glutamate efflux from rat
      cerebral cortex is calcium-independent and not due to cell damage up to 45 min.
      The inhibitory effect of GABA, clomethiazole and pentobarbitone on ischaemia
      induced glutamate efflux appears to be mediated by GABA(A) receptors. The results
      suggest that clomethiazole, unlike pentobarbitone, is able to activate the GABAA
      receptor-linked chloride channel directly and not merely potentiate the effect of
      endogenous GABA.

PMID- 10882399
TI  - Different intrinsic activities of bucindolol, carvedilol and metoprolol in human
      failing myocardium.
AB  - 1. Clinical studies have shown different effects of beta-blockers on the beta
      adrenergic system, tolerability and outcome in patients with heart failure. 2.
      The study examines beta-adrenoceptor-G-protein coupling and intrinsic activity of
      bucindolol, carvedilol and metoprolol in human ventricular myocardium. 3.
      Radioligand binding studies ([(125)I]-Iodocyanopindolol) were performed in
      membrane preparations of human failing and nonfailing myocardium. Functional
      experiments were carried out in isolated muscle preparations of human left
      ventricular myocardium from failing hearts. 4. Bucindolol and carvedilol bound
      non-selectively to beta(1)- and beta(2)-adrenoceptors and exerted guanine
      nucleotide modulatable binding. Metoprolol was 35-fold beta(1)-selective and
      lacked guanine nucleotide modulatable binding. 5. All beta-blockers antagonized
      isoprenaline-induced enhancement of contractility. 6. In preparations in which
      the coupling of the stimulatory G-protein to adenylate cyclase was facilitated by
      forskolin, bucindolol increased force of contraction in three and decreased it in
      five experiments. Carvedilol increased force in one and decreased it in six
      experiments. Metoprolol decreased force in all experiments by 89. 4+/-2.2%
      (P<0.01 metoprolol vs carvedilol and bucindolol). The negative inotropic effect
      of metoprolol was antagonized by bucindolol. 7. It is concluded that differences
      in intrinsic activity can be detected in human myocardium and have an impact on
      cardiac contractility. In human ventricular myocardium, bucindolol displays
      substantially higher intrinsic activity than metoprolol and carvedilol.
      Bucindolol can behave as partial agonist or partial inverse agonist depending on
      the examined tissue. 8. Differences in intrinsic activity may contribute to
      differences in beta-adrenoceptor regulation and possibly to differences in
      tolerability and outcomes of patients with heart failure.

PMID- 10882400
TI  - Stimulus-specific alteration of the relationship between cytosolic Ca(2+)
      transients and nitric oxide production in endothelial cells ex vivo.
AB  - 1. To investigate the quantitative relationship between elevation in the
      intracellular Ca(2+) concentration ([Ca(2+)](i)) and nitric oxide (NO)
      production, the changes in [Ca(2+)](i) and NO production were determined in
      parallel, using fluorimetry of fura-2 and 2, 3-diaminonaphthalene, respectively,
      in endothelial cells ex vivo of pig aortic valves. 2. The extent of [Ca(2+)](i)
      elevation was quantitatively assessed by two parameters: the level of peak
      [Ca(2+)](i) elevation and the area under the [Ca(2+)](i) curve during treatment
      (the integrated [Ca(2+)](i) elevation). The amount of NO production was expressed
      as a percentage of that obtained with 10 microM ATP for 3 min. 3. ATP,
      bradykinin, thrombin, and ionomycin were used as stimulation to induce NO
      production, and all these caused [Ca(2+)](i) increases and NO production in a
      concentration-dependent manner. 4. The relationships between the peak [Ca(2+)](i)
      and NO production or between the integrated [Ca(2+)](i) elevation and NO
      production were well described by a straight line. However, the slope value of
      the linear relationship in both cases varied with the type of stimulation, with
      thrombin giving the greatest value, followed by ATP, bradykinin and ionomycin. 5.
      These data suggest that in endothelial cells ex vivo: (1) [Ca(2+)](i) elevation
      regulates NO production, but (2) the peak [Ca(2+)](i) elevation- or the
      integrated [Ca(2+)](i) elevation-NO production relationships varies depending on
      the type of agonists. Our results thus demonstrate the presence of the agonists
      dependent modulation of the relationship between [Ca(2+)](i) elevation and NO
      production in endothelial cells ex vivo.

PMID- 10882401
TI  - Effect of acute nicotine administration on striatal dopamine output and
      metabolism in rats kept at different ambient temperatures.
AB  - 1. The effect of ambient temperature on the nicotine-induced (0.3, 0.5 or 0.8 mg
      kg(-1) s.c.) changes of the striatal concentrations of dopamine (DA) and its
      metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
      was studied in freely-moving rats by in vivo microdialysis. 2. At the ambient
      temperature of 30 - 33 degrees C, but not at 20 - 23 degrees C, nicotine doses of
      0.5 (P<0. 01) and 0.8 mg kg(-1) (P<0.05) significantly increased the
      extracellular DA concentration. The nicotine doses of 0.5 and 0.8 mg kg(-1)
      increased the DA metabolite levels similarly at both ambient temperatures studied
      (P</=0.0001), but the dose of 0.3 mg kg(-1) only at 30 - 33 degrees C (DOPAC:
      P<0.05; HVA: P<0.01). 3. At 30 - 33 degrees C, dihydro-beta-erythroidine (DHbetaE
      2.8 mg kg(-1) i.p.) blocked the nicotine-induced (0.5 or 0.8 mg kg(-1)) increases
      of extracellular DA concentration but only tended to antagonize the increases of
      DA metabolites. Mecamylamine (5.0 mg kg(-1) i.p.) blocked the increase of DA
      output induced by 0.5 mg kg(-1) but not that induced by 0.8 mg kg(-1) of nicotine
      and fully prevented the nicotine-induced elevations of DOPAC and HVA. 4.
      Elevation of ambient temperature did not affect the cerebral concentration of
      nicotine or the nicotine-induced elevation of serum corticosteroids. Also, the
      rectal temperatures of rats given nicotine at either ambient temperature did not
      significantly change. 5. Our results show that the nicotine-induced output of
      striatal DA is enhanced at high ambient temperature. Further, our findings
      suggest that the nicotinic cholinoceptors mediating the effects of nicotine on
      striatal DA release are different from those mediating nicotine's effects on DA
      metabolism.

PMID- 10882402
TI  - Differential A(1)-adenosine receptor reserve for inhibition of cyclic AMP
      accumulation and G-protein activation in DDT(1) MF-2 cells.
AB  - 1. The A(1)-adenosine receptor (A(1)AdoR) reserve for N(6)-cyclopentyladenosine
      (CPA) mediated inhibition of (-)isoprenaline stimulated cyclic AMP accumulation
      and stimulation of [(35)S]-guanosine-5'-O-(thiotriphosphate) (GTPgammaS) binding,
      a measure of guanine nucleotide binding protein (G-protein) activation, was
      determined in DDT(1) MF-2 cells. 2. Inactivation of the A(1)AdoRs with the
      chemoreactive ligand 8-cyclopentyl-3-[3-[[4-(fluorosulphonyl)benzoyl]oxy]propyl]
      1-p ropylx anthine (FSCPX) caused a progressive rightward shift of the
      concentration-response curves for CPA to inhibit cyclic AMP accumulation, with a
      maximum of 10 fold increase in the EC(50) value. In contrast, inactivation of
      A(1)AdoR's caused only a 1.7 fold rightward shift in the CPA concentration
      response for stimulation of [(35)S]-GTPgammaS binding. 3. The A(1)AdoR occupancy
      response relationship for CPA inhibition of cyclic AMP accumulation was
      hyperbolic with 43% receptor occupancy required to elicit the maximal response,
      i.e. a 57% A(1)AdoR reserve. In contrast, the A(1)AdoR occupancy-response
      relationship for CPA mediated stimulation of [(35)S]-GTPgammaS binding was linear
      indicating little or no receptor reserve for G-protein activation. The
      relationship between CPA stimulation of [(35)S]-GTPgammaS binding and cyclic AMP
      inhibition was also hyperbolic with 44% G-protein activation sufficient to cause
      maximal inhibition. 4. The data suggest that the A(1)AdoR reserve for CPA
      mediated inhibition of cyclic AMP accumulation occurs at the level of G-protein
      interaction with adenylyl cyclase. However, each A(1)AdoR appears to activate a
      constant fraction of the total G-protein population suggesting signal
      amplification at the receptor-G-protein level which may also contribute to the
      receptor reserve for CPA.

PMID- 10882403
TI  - Mechanisms underlying the neurokinin A-induced contraction of the pregnant rat
      myometrium.
AB  - 1. Using fura-PE3 fluorimetry and alpha-toxin permeabilization, the
      characteristics of the contractile responses to neurokinin A (NKA) were
      determined in the pregnant rat myometrium. 2. NKA induced contractions in rat
      myometrium in a concentration-dependent manner. There were no significant
      differences in the maximum contractions and EC(50) values between the pregnant
      and non-pregnant myometrium, however, the contraction of only the former was
      greatly enhanced in the presence of phosphoramidon (PPAD), an endopeptidase
      inhibitor. 3. In the pregnant myometrium, NKA induced sustained increases in
      [Ca(2+)](i) and tension in normal physiological saline solution, while only small
      transient increases in [Ca(2+)](i) and tension were observed in Ca(2+)-free
      solution. 4. Both diltiazem (10 microM) and SK-F 96365 (10 microM) significantly
      inhibited the NKA-induced elevations of [Ca(2+)](i) and tension. The effects were
      additive when these drugs were used together. 5. NKA induced a significant
      leftward shift of the [Ca(2+)](i)-tension curve obtained by changing the external
      Ca(2+) (0 - 2.5 mM) during depolarization with high K(+) solution. This Ca(2+)
      sensitizing effect by NKA was also observed in the alpha-toxin permeabilized
      myometrium. 5. These results indicated that in the pregnant rat myometrium: (1)
      the responsiveness to NKA increased, although it was masked by the increase in
      the endopeptidase activity; (2) NKA induced contractions of the myometrium by
      increasing both [Ca(2+)](i) and the myofilament Ca(2+) sensitivity and (3) The
      NKA-induced [Ca(2+)](i) elevation was partly due to the intracellular Ca(2+)
      release and mainly due to the Ca(2+) influx, which was thought to be through both
      voltage dependent calcium channels and non-specification channels.

PMID- 10882404
TI  - Potassium does not mimic EDHF in rat mesenteric arteries.
AB  - 1. K(+) has been proposed to be EDHF in small arteries. We compared ACh
      stimulated, EDHF-mediated dilatation/relaxation with raised [K(+)](o) in rat
      mesenteric arteries. 2. In pressurized arteries, ACh (10 microM) dilated all
      arteries. Raising [K(+)](o) from 5.88 to 10. 58 mM only dilated 30% of arteries.
      Ba(2+) (30 microM) did not affect dilatation to ACh, but abolished 40% of
      dilatations to raised [K(+)](o). 3. If [K(+)](o) was lowered to 1.18 mM,
      restoring [K(+)](o) to 5.88 mM produced dilatation which was depressed by Ba(2+)
      or ouabain (1 mM). Combined application of Ba(2+) and ouabain abolished
      dilatation. In 1.18 mM K(+), dilatation to ACh was depressed by ouabain, but not
      by Ba(2+). Combined application of Ba(2+) and ouabain depressed dilatation
      further. Gap junction inhibitors (Gap-27; 300 microM and 18-alpha-glycyrrhetinic
      acid; 100 microM) also depressed dilatation to ACh. 4. In arteries mounted
      isometrically, ACh (1 microM) relaxed endothelium intact (+E), but not
      endothelium denuded (-E) arteries. Raising [K(+)](o) from 5.9 - 10.9 mM failed to
      relax all arteries. When [K(+)](o) was lowered to 1 mM, raising [K(+)](o) to 6 mM
      produced relaxation. In -E arteries, relaxation was unaffected by Ba(2+) but
      abolished by ouabain. In +E arteries, Ba(2+) depressed and ouabain abolished
      relaxation. In +E arteries, with 1 mM K(+), ACh relaxation was depressed by
      ouabain but not Ba(2+). The combined application of Ba(2+) and ouabain further
      depressed relaxation. 5. In summary, both EDHF and raised [K(+)](o) dilate/relax
      rat mesenteric arteries, though sensitivities to barium and ouabain differ. K(+)
      may be a relaxing factor in this tissue, but its characteristics differ from
      EDHF. Gap junction inhibitors depress EDHF, implying an important role for myo
      endothelial gap junctions.

PMID- 10882406
TI  - Water dynamics at the binding interface of four different HLA-A2-peptide
      complexes.
AB  - Because only a limited number of MHC molecules are available for presentation of
      a large number of peptides, each of these MHC molecules must be able to bind
      promiscuously many different peptides at an affinity sufficient for stable
      presentation. Here we show, for the MHC molecule HLA-A2, that this ability may be
      facilitated by a flexible water network that forms an interface between the MHC
      molecule and the peptide. Using the SURFNET program we have computed the 'gaps'
      present in the peptide-binding groove in the X-ray structures of complexes of HLA
      A2 with four different bound peptides. The volume of these gaps increases with
      increasing peptide hydrophilicity. Using molecular dynamics simulations, we show
      that the water molecules in the binding groove of complexes of HLA-A2 with the
      more hydrophilic peptides are largely disordered, but a number of defined water
      binding sites are also discernable. Conversely, for complexes of HLA-A2 with the
      more hydrophobic peptides, the water molecules are more rigidly bound at the MHC
      peptide interface and a number of well-defined water-binding sites exist.
      However, even these well-defined sites may not be permanently occupied by the
      same water molecule and in the dynamics calculations we observed exchange of
      water molecules between such sites.

PMID- 10882405
TI  - Inhibition of NFkappaB-mediated pro-inflammatory gene expression in rat mesangial
      cells by the enolized 1,3-dioxane-4, 6-dione-5-carboxamide, CGP-43182.
AB  - 1. CGP-43182 has been described as a potent inhibitor of group IIA secreted
      phospholipase A(2) (group IIA sPLA(2)) activity in vitro. In rat mesangial cells,
      inhibition of group IIA sPLA(2) activity by CGP-43182 results in a 70% reduction
      of cytokine-stimulated prostaglandin E(2) biosynthesis, suggesting that group IIA
      sPLA(2) participates in arachidonic acid release and eicosanoid formation. Under
      these conditions the cytosolic phospholipase A(2) is not affected. 2. In
      mesangial cells, in addition to inhibition of catalytic activity, the membrane
      permeant CGP-43182 completely blocked interleukin 1beta (IL1beta)-stimulated
      group IIA sPLA(2) gene expression. 3. A further action of CGP-43182 was a
      complete inhibition of cyclo-oxygenase-2 gene expression, resulting in a drastic
      reduction of prostaglandin formation in mesangial cells. 4. Moreover, CGP-43182
      completely blocked IL1beta-induced gene expression of the inducible nitric oxide
      synthase, leading to an inhibition of cytokine-stimulated nitric oxide formation.
      5. In contrast, the stimulatory effect of the cell-permeant cyclic AMP-analogue,
      dibutyryl-cAMP, on the induction of these enzymes was not inhibited by CGP-43182.
      These data indicate that CGP-43182 interferes with IL1beta- but not cyclic AMP
      activated transcriptional regulation. 6. By studying components of the upstream
      transcription machinery, we observed an inhibition of NFkappaB activation by CGP
      43182 in IL1beta-treated cells. Moreover, we observed that CGP-43182 prevented
      the phosphorylation and proteolytic degradation of the endogenous NFkappaB
      inhibitor, IkappaB, a process necessary for NFkappaB activation. 7. From our
      data, we propose that CGP-43182 is a potent anti-inflammatory drug useful for
      preventing the consequences of a concerted action of cytokine-stimulated pro
      inflammatory genes mediated by NFkappaB.

PMID- 10882407
TI  - Class switch recombination of the chicken IgH chain genes: implications for the
      primordial switch region repeats.
AB  - In mammals and the amphibian, Xenopus, isotypes of antibodies have been shown to
      be changed through class switch recombination within the IgH chain gene locus.
      Here, we identified switch (S) repetitive sequences in the 5' introns of the Ig
      C(mu) and C(gamma) genes of the chicken. The S(mu) region is composed of two
      homologous regions, S(mu)1 and S(mu)2. The S(mu)1 region is an upstream 3.7 kb
      sequence composed of 37 repeats of a consensus sequence containing tandem repeats
      of the decamer ACCAGTATGG. The S(mu)2 region is a downstream 1.4 kb sequence
      consisting of simple tandem repeats of a decamer CCCAGTACAG. The S(gamma) region
      contains repeats of the decamer TATGGGGCAG. Analysis of chicken IgG-producing
      hybridomas revealed that the C(mu) gene was deleted from the chromosome by the
      recombination occurring between the S(mu) and S(gamma) regions. Recombination
      breakpoints at the C(mu) gene of splenocytes from an immunized chicken were
      scattered around the S(mu) region and two such breakpoints, the precise position
      of which were determined, were located within possible hairpin loop structures at
      the palindromic sequence of S(mu)1. A primordial palindromic sequence from which
      the prevalent switch repeat motifs of mammals, chickens and amphibians may have
      diverged is presented.

PMID- 10882408
TI  - Non-overlapping Fas- and BCL-2-regulated death pathways in IgG2a(b)-producing B
      cells.
AB  - Using perforin (Pfp)- and/or Fas-dependent cytotoxic pathways, T splenocytes from
      Igh(a/a) mice are able in vivo to totally and chronically eliminate congenic
      Igh(b/b) B cells committed to IgG2a(b) production. This phenomenon leads to a
      characteristic absence of serum IgG2a(b) expression (IgG2a(b) allotype
      suppression) in, for instance, histocompatible Igh(a/b) or Igh(b/b) mice, having
      neonatally received such T cells. Because the study of the protective role of BCL
      2 oncoprotein against Fas-mediated cell death has generated contradictory
      findings, we examined the possible impact of constitutive overexpression of
      transgenic human BCL-2 protein in Igh(b/b) B cells when the latter were exposed
      in vivo exclusively with the Fas-dependent, anti-IgG2a(b) T cell activity of
      Igh(a/a) Pfp(0/0) mice. We observed that, despite high intracellular expression
      of functional transgenic BCL-2 and no up-regulation of the principal BCL-2
      inhibitors in whole Igh(b/b) B cells, total, chronic and specific IgG2a(b)
      suppression was exerted by Igh(a/a) Pfp(0/0) cytotoxic T cells. These data show
      that, in this model of negative regulation of Ig production, Fas- and BCL-2
      regulated mechanisms belong to non-overlapping death pathways at the level of
      IgG2a(b)-producing B cells, targets of Igh(a/a) T cell-mediated cytotoxicity.
      Thus, in these mature B cells, the Fas signaling-directly operating via caspase 8
      does not involve a mitochondria-dependent pathway regulated by BCL-2.

PMID- 10882409
TI  - IFN-gamma and IL-4 differently regulate inducible NO synthase gene expression
      through IRF-1 modulation.
AB  - NO is a labile radical involved in several immunological, antimicrobial and
      inflammatory processes. In macrophages, NO formation is catalyzed by the cytokine
      inducible enzyme inducible NO synthase (iNOS). The importance of IFN regulatory
      factor (IRF)-1 and of the signal transducers and activators of transcription
      (STAT)-1 for the induction of iNOS gene expression in response to IFN-gamma has
      been well defined. Here, we investigated the molecular events responsible for the
      inhibition of iNOS gene expression by IL-4 in the murine macrophage cell line
      RAW264.7. Unidirectional deletion analysis on iNOS promoter demonstrated that an
      IFN-stimulated responsive element (ISRE), contained in the -980 to -765 bp region
      of the iNOS promoter, may be involved in the IL-4-mediated inhibition of IFN
      gamma-inducible iNOS transcription. Accordingly, the IFN-gamma-induced binding
      activity of IRF-1 to the ISRE sequence was reduced in cells pre-treated with IL
      4, while the binding activity of STAT-1 to the STAT-binding element (SBE) within
      the same region of the iNOS promoter remained unaffected. Moreover, IL-4 even
      down-regulated IFN-gamma-inducible expression of IRF-1 mRNA. This could be
      related to a transcriptional mechanism by which IL-4 and IFN-gamma differentially
      influence the trans-acting activity of the STAT factors binding to SBE within the
      IRF-1 promoter. SBE is targeted by IFN-gamma-inducible STAT-1 and by IL-4
      inducible STAT-6. Although STAT-6 has no trans-acting function on iNOS gene
      expression, it is able to inhibit the IFN-gamma-induced expression of IRF-1.
      Thus, IL-4 may down-regulate IFN-gamma-inducible iNOS transcription by activation
      of STAT-6 which in turn inhibits IRF-1 expression.

PMID- 10882410
TI  - The interface between innate and acquired immunity: glycolipid antigen
      presentation by CD1d-expressing dendritic cells to NKT cells induces the
      differentiation of antigen-specific cytotoxic T lymphocytes.
AB  - In vivo administration of NKT cell ligand, alpha-galactosylceramide (alpha
      GalCer), caused the activation of NKT cells to induce a strong NK activity and
      cytokine production by CD1d-restricted mechanisms. Surprisingly, we also found
      that alpha-GalCer induced the activation of immunoregulatory cells involved in
      acquired immunity. Specifically, in vivo administration of alpha-GalCer resulted
      in the induction of the early activation marker CD69 on CD4(+) T cells, CD8(+) T
      cells and B cells in addition to macrophages and NKT cells. However, no
      significant induction of CD69 was observed on cells from CD1d- or V(alpha)14 NKT
      deficient mice, indicating an essential role for the interaction between NKT
      cells and CD1d-expressing dendritic cells (DC) in the activation of acquired
      immunity in response to alpha-GalCer. Indeed, in vivo injection of alpha-GalCer
      resulted not only in the activation of NKT cells but also in the generation of
      CD69(+)CD8(+) T cells possessing both cytotoxic T lymphocyte (CTL) activity and
      IFN-gamma-producing ability. Tumor-specific CTL generation was also accelerated
      by alpha-GalCer. The critical role of CD40-CD40 ligand (CD40L)-mediated NKT-DC
      interaction during the development of CD69(+)CD8(+) CTL by alpha-GalCer was
      demonstrated by blocking experiments using anti-CD40L mAb. These findings provide
      direct evidence for a critical role of CD1d-restricted NKT cells and DC in
      bridging innate and acquired immunity.

PMID- 10882411
TI  - STAT6 is required for the regulation of IL-4-induced cytoskeletal events in B
      cells.
AB  - During lymphocyte activation, changes in cell morphology are commonly observed.
      This reflects cell functions important for the regulation of immune responses
      such as cell adhesion or cell migration. Notably, IL-4 has been shown to induce
      adhesion and locomotion in B cells, and we have recently described that IL-4
      causes dramatic changes in B cell morphology. Thus, such B cells spread with
      dendritic cell protrusions and produce microvilli-like structures. The molecular
      mechanisms by which IL-4 induces these complex changes are currently unknown. Two
      signal transduction pathways are well described for IL-4, i.e. one involving
      insulin receptor substrate (IRS)-2 and a Janus kinase (JAK)/ signal transducer
      and activator of transcription (STAT) pathway mediated by STAT6. In this study we
      therefore used B cells from STAT6-deficient mice to address the question of a
      possible STAT6 dependence in IL-4-induced morphology changes. By light and
      electron microscopy, cell spreading and polarization were found to be severely
      impaired and microvilli formation was reduced. In contrast, only mild impairment
      was observed in cell adhesion in B cells from STAT6-deficient mice. Our results
      show that adhesion can be induced in the absence of STAT6. However, expression of
      STAT6 is necessary for optimal responses in both cell adhesion and microvilli
      induction. STAT6 is also essential to allow an IL-4-dependent spreading or
      polarization response. A possible interpretation of our results is that STAT6
      dependent expression of a specific gene or genes is required for IL-4 to affect
      changes in B cell morphology.

PMID- 10882412
TI  - Loss of CD28 expression on CD8(+) T cells is induced by IL-2 receptor gamma chain
      signalling cytokines and type I IFN, and increases susceptibility to activation
      induced apoptosis.
AB  - CD8(+)CD28(-) T cells are selectively expanded during viral infections,
      indicating their importance in anti-viral immune responses. Since little is known
      about the differentiation of CD8(+)CD28(-) cells, we investigated the generation,
      function and survival characteristics of this subset. In healthy individuals
      CD8(+)CD28(-) T cells contained more elevated levels of perforin and IFN-gamma
      than the CD8(+)CD28(+) subset, indicating that they can have an effector
      function. CD8(+)CD28(-) cells were selectively expanded when activated
      CD8(+)CD28(+) T cells were cultured in IL-2, IL-7 or IL-15. Moreover, the
      generation of CD8(+)CD28(-) cells was accelerated by type I IFN suggesting that
      these cytokines which are released during viral infections influence CD8(+) T
      cell differentiation. We did not observe re-expression of CD28 by CD8(+)CD28(-) T
      cells in any of the experiments performed. Activated T cells are susceptible to
      activation-induced cell death (AICD) if re-stimulated in the absence of co
      stimuli. AICD was induced in both CD28(+) and CD28(-) subsets of activated T
      cells when stimulated with anti-CD3 antibody in the absence of co-stimuli but the
      magnitude of death was greater in the CD28(-) subset. While co-stimulation
      through LFA-1 (CD11a and CD18) significantly reduced AICD in the CD8(+)CD28(+)
      subset, death was not prevented in CD8(+)CD28(-) cells. These results suggest
      that CD8(+)CD28(-) T cells are more functionally differentiated than the
      CD8(+)CD28(+) subset and indicate they may represent a terminally differentiated
      effector population which is destined for clearance by apoptosis at the end of
      the immune response.

PMID- 10882413
TI  - Expression of a complete and functional complement system by human neuronal cells
      in vitro.
AB  - We demonstrate in vitro expression of complement components, i.e. C3, factor H
      (FH), factor B (FB), C4, C1-inhibitor (C1-inh), C1q, C5, C6, C7 and C9, by four
      human neuroblastoma cell lines IMR32, SKNSH, SH-SY5Y and KELLY. Activating
      proteins C4, C9 and C1q, and regulatory proteins FH and C1-inh were produced
      constitutively by the four cell lines. C3, C6 and FB were mainly produced by
      SKNSH and SH-SY5Y. Western blot experiments showed that secreted proteins were
      structurally similar to their serum counterparts. An additional polypeptide of 43
      kDa with FH immunoreactivity was detected, which could correspond to the N
      terminal truncated form found in plasma. Regulation of complement expression by
      inflammatory cytokines, lipopolysaccharide and dexamethasone was tested in vitro.
      These factors had no significant effects on activating synthesis of components
      C3, FB and C4, but expression of regulating components C1-inh and FH was strongly
      increased particularly by IFN-gamma and tumor necrosis factor-alpha. The rate of
      synthesis of complement components was dependent on the differentiation of
      neuroblastoma cells. This effect of differentiation was also observed on normal
      rat neurons. Rat cerebellar granule cells constitutively expressed mRNA for C4
      and C1q, but expression of C3 mRNA was induced by differentiation. This study
      shows that neurons could be another local source of complement in the brain,
      besides astrocytes and microglia. Human neuroblastoma cell lines can constitute
      an interesting model to analyze complement biosynthesis by human neurons. Local
      complement expression by neurons in vivo may be implicated in some physio
      pathological processes.

PMID- 10882414
TI  - Failure of rIL-12 administration to inhibit established IgE responses in vivo is
      associated with enhanced IL-4 synthesis by non-B/non-T cells.
AB  - Administration of rIL-12 offers a widely successful tactic for preferential
      induction of type 1 immune responses in vivo. Its use to modulate ongoing
      cytokine or effector responses has proven to be substantially more difficult.
      Immediate hypersensitivity is the most common human immunologic disease. Here,
      rIL-12 was administered to C57Bl/6 and outbred CD1 mice with ongoing ovalbumin
      (OVA)-specific IgE responses in an attempt to redirect established type 2
      cytokine and antibody production. Despite use of a broad range of treatment
      protocols for >4 months following initial immunization, recall IgE responses were
      consistently unaffected. rIL-12-treated mice exhibited strong in vivo and in
      vitro IFN-gamma responses, increased approximately 40-fold relative to controls,
      but also markedly enhanced (15- to 20-fold) OVA-specific IL-4 production. CD4 T
      cell function was successfully transformed from a type 2- to a type 1-dominated
      pattern following long-term IL-12 administration in vivo, as measured by strongly
      reduced IL-4 and IL-10 responses in antigen-stimulated primary culture, and 5
      fold reductions in the frequencies of IL-4- and IL-10-producing OVA-specific CD4
      T cells. However, chronically rIL-12-treated mice exhibited increased numbers of
      non-B/non-T cells that when re-stimulated with specific allergen, produce IL-4 at
      levels 20-fold higher than did CD4 T cells while IL-13 responses are unaffected.
      Collectively, the data indicate that even effectively shifting CD4 T cell
      activation from a type 2- to a type 1-dominated response does not in itself lead
      to altered effector (IgE) responses upon antigen re-exposure.

PMID- 10882415
TI  - Programming for cytotoxic effector function occurs concomitantly with CD4
      extinction during CD8(+) T cell differentiation in the thymus.
AB  - CD4(+) T cells are generally specialized to function as helper cells and CD8(+) T
      cells are generally specialized to function as cytotoxic effector cells. To
      explain how such concordance is achieved between co-receptor expression and
      immune function, we considered two possibilities. In one case, immature
      CD4(+)CD8(+) thymocyte precursors might first down-regulate expression of one co
      receptor molecule, with the remaining co-receptor molecule subsequently
      activating the appropriate helper or cytotoxic functional program. Alternatively,
      we considered that the same intrathymic signals that selectively extinguished
      expression of one or the other co-receptor molecule might simultaneously initiate
      the appropriate helper or cytotoxic functional program. In the present study, we
      attempted to distinguish between these alternatives by examining thymocyte
      precursors of CD8(+) T cells for expression of Cathepsin C and Cathepsin W,
      molecules important for cytotoxic effector function. We report in developing
      thymocytes that Cathepsin C and Cathepsin W are expressed coordinately with
      extinction of CD4 co-receptor expression. We conclude that CD4 extinction and
      initiation of the cytotoxic functional program occurs simultaneously during
      differentiation of CD8(+) T cells in the thymus.

PMID- 10882416
TI  - A self-hsp60 peptide acts as a partial agonist inducing expression of B7-2 on
      mycobacterial hsp60-specific T cells: a possible mechanism for inhibitory T cell
      regulation of adjuvant arthritis?
AB  - We previously reported that resistance to the induction of adjuvant arthritis
      after preimmunization with mycobacterial hsp60 was mediated by T cells
      recognizing a conserved epitope (M256-270) of mycobacterial hsp60. These T cells
      were cross-reactive with the homologous rat hsp60 peptide sequence and the
      natural self-epitope on stressed antigen-presenting cells. Recognition of peptide
      M256-265, the conserved core of peptide M256-270, was shown to be essential for
      the generation of self-reactive T cells. The rat homologue of peptide M256-265,
      peptide R256-265, differs with three conservative amino acid substitutions from
      the mycobacterial core peptide. Thus peptide R256-265 could act as an altered
      peptide ligand with the potential of inducing a different functional phenotype in
      M256-270-specific T cells. We now show that peptide R256-265 was recognized by
      M256-270-specific T cells as a partial agonist, inducing TCR down-regulation and
      up-regulation of activation/adhesion molecules in the absence of proliferative
      responses. Peptide R256-265 did not induce anergy but induced B7-2 (but not B7-1)
      expression on M256-270-specific T cells, as opposed to the mycobacterial peptide,
      which preferentially induced B7-1. These effects were more pronounced at low
      peptide concentrations. Therefore also in vivo at the more relevant low
      physiological level of expression, the self-hsp could induce such phenotype. It
      is discussed how this selective up-regulation of B7-2 expression on (self-hsp60)
      autoreactive T cells might be a way by which destructive autoimmune responses are
      controlled.

PMID- 10882418
TI  - Molecular evidence for antigen-driven immune responses in cardiac lesions of
      rheumatic heart disease patients.
AB  - Rheumatic heart disease (RHD) is a sequel of post-streptococcal throat infection.
      Molecular mimicry between streptococcal and heart components has been proposed as
      the triggering factor of the disease, and CD4(+) T cells have been found
      predominantly at pathological sites in the heart of RHD patients. These
      infiltrating T cells are able to recognize streptococcal M protein peptides,
      involving mainly 1-25, 81-103 and 163-177 N-terminal amino acids residues. In the
      present work we focused on the TCR beta chain family (TCR BV) usage and the
      degree of clonality assessed by beta chain complementarity-determining region
      (CDR)-3 length analysis. We have shown that in chronic RHD patients, TCR BV usage
      in peripheral blood mononuclear cells (PBMC) paired with heart-infiltrating T
      cell lines (HIL) is not suggestive of a superantigen effect. Oligoclonal T cell
      expansions were more frequently observed in HIL than in PBMC. Some major BV
      expansions were shared between the mitral valve (Miv) and left atrium (LA) T cell
      lines, but an in-depth analysis of BJ segments usage in these shared expansions
      as well as nucleotide sequencing of the CDR3 regions suggested that different
      antigenic peptides could be predominantly recognized in the Miv and the
      myocardium. Since different antigenic proteins probably are constitutively
      represented in myocardium and valvular tissue, these findings could suggest a
      differential epitope recognition at the two lesional heart sites after a common
      initial bacterial challenge.

PMID- 10882417
TI  - Novel molecular mechanisms of dendritic cell-induced T cell activation.
AB  - In this study we have re-examined the molecular mechanisms involved in activation
      of T cells by dendritic cells (DC). Human peripheral blood DC (PBDC) were derived
      by 2 h adhesion followed by 7 day culture in a combination of granulocyte
      macrophage colony stimulating factor and IL-4, and depletion of residual T and B
      cells. These PBDC were used to induce autologous T cell proliferation in a CD3
      dependent response, and antibodies against CD11a/18 and CD86 were used as control
      inhibitors of accessory function. Antibodies against five of the cell surface
      molecules that we have recently identified on the surface of DC, CD13, CD87,
      CD98, CD147 and CD148, and an antibody which recognizes a molecule that has not
      as yet been identified, all inhibited the CD3-induced T cell proliferation. These
      findings were observed not only when antibodies were present throughout the
      culture, but also when they were prepulsed on to the surface of the DC,
      suggesting the inhibition was mediated via the antigen-presenting cells rather
      than the T cell. The same set of antibodies also inhibited an allospecific mixed
      lymphocyte reaction, confirming that the inhibitory effect was not dependent on
      the use of a CD3 antibody as the stimulating agent. All the antibodies of known
      specificity inhibited both CD4 and CD8 T cells equally. Unlike CD87, CD98 and
      CD147 antibodies, which inhibited activation of both CD45RA (naive) T cells and
      CD45RO (memory) T cells, CD13 and CD148 appeared to be involved in activation of
      naive cells only. The molecules identified in this study have not previously been
      demonstrated to play a role as accessory molecules on DC, the cells that are
      pivotal for immune induction. Therefore they may provide new potential targets
      for modulation of the immune response at the APC level.

PMID- 10882419
TI  - Suppression of insulitis and diabetes in B cell-deficient mice treated with
      streptozocin: B cells are essential for the TCR clonotype spreading of islet
      infiltrating T cells.
AB  - In order to clarify the role of B cells in the development of insulitis and
      diabetes, B cell-deficient (B(-)) mice treated with streptozocin (STZ) were
      studied. The extent of insulitis and the cumulative incidence of diabetes were
      significantly suppressed in B(-) mice (P < 0.0001), indicating that B cells are
      crucial for the progression of insulitis and diabetes. Accumulation of both
      CD4(+) T cells and B cells was observed in islets of B(+) mice, while CD4(+) T
      cells but not B cells were found in B(-) mice. A few CD8(+) T cells and
      macrophages were detectable in both types of mice. The immunohistochemical study
      did not reveal any change in the subpopulations of infiltrating lymphocytes
      except for the absence of B cells in the B(-) mice. TCR V(beta) gene repertoire
      usage of islet-infiltrating T cells was restricted to some extent in the B(+) or
      B(-) mice, but there was no significant difference between the B(+) and B(-)
      mice, suggesting that the initial islet-reactive T cell response can occur in the
      absence of B cells. In contrast, TCR clonotype spreading of islet-infiltrating T
      cells was significantly suppressed in B(-) mice compared with B(+) mice (P <
      0.0001). These data suggest that initial priming of T cells is not impaired and
      TCR V(beta) repertoire usage is not limited by the lack of B cells, while B cells
      are important essentially for the spreading of islet-infiltrating clonal T cells
      in autoimmune diabetic mice induced with STZ.

PMID- 10882420
TI  - The TATA binding protein, c-Myc and survivin genes are not somatically
      hypermutated, while Ig and BCL6 genes are hypermutated in human memory B cells.
AB  - Immunoglobulin (IG:) genes are hypermutated in mature B cells after interaction
      with antigen and T cells in a germinal center reaction. We and others have
      recently shown that the human BCL6 gene is also hypermutated in human peripheral
      blood memory B cells and tonsils. A preliminary analysis of other non-Ig genes (c
      MYC:, S14 and AFP) suggested that they were not mutated in memory B cells. We
      have now performed an in-depth analysis of three non-Ig genes that are expressed
      in germinal center B cells in two human donors in whom BCL6 is highly mutated. It
      was found that the TATA binding protein (TBP), c-MYC: and survivin genes are not
      hypermutated. This lack of targeting by the Ig hypermutation mechanism must be
      due to the lack of regulatory DNA elements, since the primary sequences of the
      three tested genes have at least as high intrinsic mutability indices as the BCL6
      gene.

PMID- 10882421
TI  - Peripheral blood extrathymic CD4(+)CD8(+) T cells with high cytotoxic activity
      are from the same lineage as CD4(+)CD8(-) T cells in cynomolgus monkeys.
AB  - We have previously reported that CD4/CD8 double-positive (DP) T cells with the
      resting memory phenotype are present in the periphery of healthy cynomolgus
      monkeys. In the present study, we performed functional studies on the T cells.
      The expression of CD4 and CD8 on DP, CD4 single-positive (SP) or CD8 SP T cells
      was stable in cultures with either mitogen or anti-CD3 antibody stimulation. In
      spite of lacking CD28 expression, DP T cells showed similar proliferative ability
      and apoptosis sensitivity to CD4 SP and CD8 SP T cells. DP T cells showed both
      helper and cytotoxic activities. Although the helper activity of DP T cells was
      lower than that of CD4 SP T cells, cytotoxic activity was comparable to that of
      CD8 SP T cells. Fresh DP T cells killed target cells mainly by the perforin
      granzyme pathway. In addition, fresh DP T cells expressed a high level of mRNA
      for IFN-gamma and produced a high level of IFN-gamma when they were activated by
      anti-CD3 antibody ligation. On the other hand, several expanded DP T cell clones
      shared TCR V(beta) with expanded CD4 SP T cell clones, strongly suggesting that
      those two corresponding clones with DP and CD4 SP phenotypes might be derived
      from the same ancestor T cell. These results showed that the DP T cells are a
      novel T cell subset with functions overlapping with those of CD4 SP and CD8 SP T
      cells, and that they might play protective and regulatory roles in secondary
      immune response in cynomolgus monkeys.

PMID- 10882422
TI  - Thymic vasculature: organizer of the medullary epithelial compartment?
AB  - The epithelial component of the thymic environment is organized into discrete
      cortical and medullary compartments that mediate different aspects of thymocyte
      differentiation. The processes controlling the growth and organization of these
      epithelial compartments are poorly defined. In this study we have used a novel
      approach to define the three-dimensional organization of thymic epithelial (TE)
      compartments to demonstrate that the organization of the medullary TE compartment
      is very complex. A spatial relationship of medullary thymic epithelium with
      vascular elements of the thymus was demonstrated by simultaneous
      immunohistochemical labeling of vascular elements and medullary TE. Medullary TE
      was often arranged as perivascular cuffs surrounding intermediate-sized vessels,
      but was not associated with either the capillary network or large centrally
      located vessels. Similar analyses of RAG-2(-/-) thymi revealed a striking
      physical association of medullary TE with vascular elements. Ultrastructural
      analysis of the RAG-2(-/-) thymus indicated a preferential association of focal
      accumulations of medullary TE with post-capillary venules. These data suggest
      that discrete segments of the thymic vasculature provide cues that act in concert
      with thymocyte-derived stimuli to effect normal development of the thymic
      environment.

PMID- 10882424
TI  - Ubiquitination and endocytosis of plasma membrane proteins: role of Nedd4/Rsp5p
      family of ubiquitin-protein ligases.
AB  - In addition to its well-known role in recognition by the proteasome, ubiquitin
      conjugation is also involved in downregulation of membrane receptors,
      transporters and channels. In most cases, ubiquitination of these plasma membrane
      proteins leads to their internalization followed by targeting to the
      lysosome/vacuole for degradation. A crucial role in ubiquitination of many plasma
      membrane proteins appears to be played by ubiquitin-protein ligases of the
      Nedd4/Rsp5p family. All family members carry an N-terminal Ca2+-dependent
      lipid/protein binding (C2) domain, two to four WW domains and a C-terminal
      catalytic Hect-domain. Nedd4 is involved in downregulation of the epithelial Na+
      channel, by binding of its WW domains to specific PY motifs of the channel.
      Rsp5p, the unique family member in S. cerevisiae, is involved in ubiquitin
      dependent endocytosis of a great number of yeast plasma membrane proteins. These
      proteins lack apparent PY motifs, but carry acidic sequences, and/or
      phosphorylated-based sequences that might be important, directly or indirectly,
      for their recognition by Rsp5p. In contrast to polyubiquitination leading to
      proteasomal recognition, a number of Rsp5p targets carry few ubiquitins per
      protein, and moreover with a different ubiquitin linkage. Accumulating evidence
      suggests that, at least in yeast, ubiquitin itself may constitute an
      internalization signal, recognized by a hypothetical receptor. Recent data also
      suggest that Nedd4/Rsp5p might play a role in the endocytic process possibly
      involving its C2 domain, in addition to its role in ubiquitinating endocytosed
      proteins.

PMID- 10882425
TI  - The apical membrane glycocalyx of MDCK cells.
AB  - The microenvironment near the apical membrane of MDCK cells was studied by
      quantitation of the fluorescence of wheat germ agglutinin attached to fluorescein
      (WGA). WGA was shown to bind to sialic acid residues attached to galactose at the
      alpha-2,3 position in the glycocalyx on the apical membrane. Young MDCK cells (5
      8 days after splitting) showed a patchy distribution of WGA at stable sites that
      returned to the same locations after removal of sialic acid residues by
      neuraminidase treatment. Other lectins also showed stable binding to patches on
      the apical membrane of young cells. The ratio of WGA fluorescence emission at two
      excitation wavelengths was used to measure near-membrane pH. The near-membrane pH
      was markedly acidic to the pH 7.4 bathing solution in both young and older cells
      (13-21 days after splitting). Patches on the apical membrane of young cells
      exhibited a range of near-membrane pH values with a mean +/- SEM of 6.86 +/- 0.04
      (n = 121) while the near-membrane pH of older cells was 6.61 +/- 0.04 (n = 120)
      with a uniform WGA distribution. We conclude that the distribution of lectin
      binding sites in young cells reflects the underlying nonrandom location of
      membrane proteins in the apical membrane and that nonuniformities in the pH of
      patches may indicate regional differences in membrane acid-base transport as well
      as in the location of charged sugars in the glycocalyx.

PMID- 10882426
TI  - Muscarinic activation of BK channels induces membrane oscillations in glioma
      cells and leads to inhibition of cell migration.
AB  - Patients with cerebral tumors often present with elevated levels of acetylcholine
      (ACh) in their cerebrospinal fluid. This motivated us to investigate
      physiological effects of ACh on cultured human astrocytoma cells (U373) using a
      combination of videomicroscopy, calcium microspectrofluorimetry and perforated
      patch-clamp recording. Astrocytoma cells exhibited the typical morphological
      changes associated with cell migration; polarized cells displayed prominent
      lamellipodia and associated membrane ruffling at the anterior of the cell, and a
      long tail region that periodically contracted into the cell body as the cell
      moved forward. Bath application of the ACh receptor agonist, muscarine,
      reversibly inhibited cell migration. In conjunction with this inhibition, ACh
      induced a dose-dependent, biphasic increase in resting intracellular free calcium
      concentration ([Ca2+]i) associated with periodic Ca2+ oscillations during
      prolonged ACh applications. The early transient rise in [Ca2+]i was abolished by
      ionomycin and thapsigargin but was insensitive to caffeine and ryanodine while
      the plateau phase was strictly dependent on external calcium. The Ca2+ response
      to ACh was mimicked by muscarine and abolished by the muscarinic antagonists,
      atropine or 4-DAMP, but not by pirenzepine. Using perforated patch-clamp
      recordings combined with fluorescent imaging, we demonstrated that ACh-induced
      [Ca2+]i oscillations triggered membrane voltage oscillations that were due to the
      activation of voltage-dependent, Ca2+-sensitive K+ currents. These K+ currents
      were blocked by intracellular injection of EGTA, or by extracellular application
      of TEA, quinine, or charybdotoxin, but not by apamin. These studies suggest that
      activation of muscarinic receptors on glioma cells induce the release of Ca2+
      from intracellular stores which in turn activate Ca2+-dependent (BK-type) K+
      channels. Furthermore, this effect was associated with inhibition of cell
      migration, suggesting an interaction of this pathway with glioma cell migration.

PMID- 10882427
TI  - Electrogenic properties of the sodium pump in a dynamic model of membrane
      transport.
AB  - The general purpose of this theoretical work is to contribute to understand the
      physiological role of the electrogenic properties of the sodium pump, by studying
      a dynamic model that integrates diverse processes of ionic and water transport
      across the plasma membrane. For this purpose, we employ a mathematical model that
      describes the rate of change of the intracellular concentrations of Na+, K+ and
      Cl-, of the cell volume, and of the plasma membrane potential (Vm). We consider
      the case of a nonexcitable, nonpolarized cell expressing the sodium pump; Na+,
      K+, Cl- and water channels, and cotransporters of KCl and NaCl in its plasma
      membrane. We particularly analyze here the conditions under which the
      physiological Vm can be generated in a predominantly electrogenic fashion, as a
      result of the activity of the sodium pump. A major conclusion of this study is
      that, for the cell model considered, a low potassium permeability is not a
      sufficient condition for a predominantly electrogenic generation of the Vm by the
      sodium pump. The presence of an electroneutral exchange of Na+ and K+ represents
      a necessary additional requirement.

PMID- 10882428
TI  - Apical Na+-Cl- symport in rabbit gallbladder epithelium: a thiazide-sensitive
      cotransporter (TSC).
AB  - Cl- apically enters the epithelium of rabbit gallbladder by a Na+-Cl- symport,
      sensitive to hydrochlorothiazide (HCTZ). Since HCTZ also activates an apical SITS
      sensitive Cl- conductance (G(Cl)), the symport inhibition might be merely due to
      a short circuit of the symport by G(Cl) rather than to a direct action of HCTZ on
      the symporter. To examine whether the symport is directly inhibited by HCTZ and
      whether the symporter belongs to the family of thiazide-sensitive cotransporters
      (TSC), radiochemical measurements of the apical Cl- uptake, electrophysiological
      determinations of intracellular Cl- and Na+ activities (a(i,Cl) and a(i,Na)) with
      selective theta microelectrodes and molecular biology methods were used. The 13Cl
      uptake proved to be a measurement of the apical unidirectional Cl- influx (Jmc)
      and of the symport only (without backflux components), with measuring times of 45
      sec under all experiment conditions; its inhibition by HCTZ was unaffected by
      G(Cl) activation or abolition. After HCTZ treatment the decrease in a(i,Cl)
      (measured as the initial rate or in 3 min) was larger than the decrease in
      a(i,Na). The difference was reduced to one third in a group of epithelia in which
      the elicited G(Cl) was reduced to one third; moreover it was abolished in any
      case when G(Cl) was abolished with 10(-4) M SITS. The SITS-insensitive rate of
      a(i,Cl) decrease was equal to that of the a(i,Na) decrease in any case. Thus the
      a(i,Cl) decrease displays a component dependent on G(Cl) activation and a second
      component dependent on symport inhibition. Using the RT-PCR technique a cDNA
      fragment was obtained that was 99% identical to the corresponding region of the
      rabbit renal TSC isoform. The results indicate that in rabbit gallbladder
      epithelium HCTZ displays a dual action, namely G(Cl) activation and Na+-Cl-
      symport inhibition. This Na+-Cl- symporter is the first TSC found to be
      functionally expressed in a nonrenal or nonrenal-like epithelium.

PMID- 10882429
TI  - The role of membrane lateral tension in calcium-induced membrane fusion.
AB  - Calcium-induced fusion of liposomes was studied with a view to understand the
      role of membrane tension in this process. Lipid mixing due to fusion was
      monitored by following fluorescence of rhodamine-phosphatidyl-ethanolamine
      incorporated into liposomal membrane at a self-quenching concentration. The
      extent of lipid mixing was found to depend on the rate of calcium addition: at
      slow rates it was significantly lower than when calcium was injected instantly.
      The vesicle inner volume was then made accessible to external calcium by adding
      calcium ionophore A23187. No effect on fusion was observed at high rates of
      calcium addition while at slow rates lipid mixing was eliminated. Fusion of
      labeled vesicles with a planar phospholipid membrane (BLM) was studied using
      fluorescence microscopy. Above a threshold concentration specific for each ion,
      Ca2+, Mg2+, Cd2+ and La3+ induce fusion of both charged and neutral membranes.
      The threshold calcium concentration required for fusion was found to be dependent
      on the vesicle charge, but not on the BLM charge. Pretreatment of vesicles with
      ionophore and calcium inhibited vesicle fusion with BLM. This effect was
      reversible: chelation of calcium prior to the application of vesicle to BLM
      completely restored their ability to fuse. These results support the hypothesis
      that tension in the outer monolayer of lipid vesicle is a primary reason for
      membrane destabilization promoting membrane fusion. How this may be a common
      mechanism for both purely lipidic and protein-mediated membrane fusion is
      discussed.

PMID- 10882431
TI  - Heterogeneous Cell Density and Genetic Structure of Bacterial Pools Associated
      with Various Soil Microenvironments as Determined by Enumeration and DNA
      Fingerprinting Approach (RISA).
AB  - The cell density and the genetic structure of bacterial subcommunities (further
      named pools) present in the various microenvironments of a silt loam soil were
      investigated. The microenvironments were isolated first using a procedure of soil
      washes that separated bacteria located outside aggregates (outer part) from those
      located inside aggregates (inner part). A nondestructive physical fractionation
      was then applied to the inner part in order to separate bacteria located inside
      stable aggregates of different size (size fractions, i.e., two macroaggregate
      fractions, two microaggregate fractions, and the dispersible day fraction).
      Bacterial densities measured by acridine orange direct counts (AODC) and viable
      heterotrophic (VH) cell enumerations showed the heterogeneous quantitative
      distribution of cells in soil. Bacteria were preferentially located in the inner
      part with 87.6% and 95.4% of the whole AODC and VH bacteria, respectively, and in
      the microaggregate and dispersible clay fractions of this part with more than 70%
      and 80% of the whole AODC and VH bacteria, respectively. The rRNA intergenic
      spacer analysis (RISA) was used to study the genetic structure of the bacterial
      pools. Different fingerprints and consequently different genetic structures were
      observed between the unfractionated soil and the microenvironments, and also
      among the various microenvironments, giving evidence that some populations were
      specific to a given location in addition to the common populations of all the
      microenvironments. Cluster and multivariate analysis of RISA profiles showed the
      weak contribution of the pools located in the macroaggregate fractions to the
      whole soil community structure, as well as the clear distinction between the pool
      associated to the macroaggregate fractions and the pools associated to the
      microaggregate ones. Furthermore, these statistical analyses allowed us to
      ascertain the influence of the clay and organic matter content of
      microenvironments on the genetic structure relatedness between pools.

PMID- 10882430
TI  - HCO3- transport in a mathematical model of the pancreatic ductal epithelium.
AB  - We have used computer modeling to investigate how pancreatic duct cells can
      secrete a fluid containing near isotonic (approximately 140 mM) NaHCO3.
      Experimental data suggest that NaHCO3 secretion occurs in three steps: (i)
      accumulation of HCO3- across the basolateral membrane of the duct cell by
      Na(HCO3)n cotransporters, Na+/H+ exchangers and proton pumps; (ii) secretion of
      HCO3- across the luminal membrane on Cl-/HCO3- antiporters operating in parallel
      with Cl- channels; and (iii) diffusion of Na+ through the paracellular pathway.
      Programming the currently available experimental data into our computer model
      shows that this mechanism for HCO3- secretion is deficient in one important
      respect. While it can produce a relatively large volume of a HCO3(-)-rich fluid,
      it can only raise the luminal HCO3- concentration up to about 70 mM. To achieve
      secretion of 140 mM NaHCO3 by the model it is necessary to: (i) reduce the
      conductive Cl- permeability and increase the conductive HCO3- permeability of the
      luminal membrane of the duct cell, and (ii) reduce the activity of the luminal Cl
      /HCO3- antiporters. Under these conditions most of the HCO3- is secreted via a
      conductive pathway. Based on our data, we propose that HCO3- secretion occurs
      mainly by the antiporter in duct segments near the acini (luminal HCO3-
      concentration up to approximately 70 mM), but mainly via channels further down
      the ductal tree (raising luminal HCO3- to approximately 140 mM).

PMID- 10882432
TI  - Characterization of Microbial Consortia in Paddy Rice Soil by Phospholipid
      Analysis.
AB  - Microbial biomass and community structure in paddy rice soil during the
      vegetation period of rice were estimated by analysis of their phospholipid fatty
      acids (PLFA), hydroxy fatty acids of lipopolysaccharides (LPS-HYFA), and
      phospholipid ether lipids (PLEL) directly extracted from the soil. A clear change
      in the composition of the community structure at different sampling periods was
      observed, indicated by the principal component analysis of the PLFA. A dramatic
      decline of ester-linked PLFA was observed in the soil samples taken at the second
      sampling time. In contrast to the ester-linked PLFA, the non-ester-linked PLFA
      composition did not change. The hydroxy fatty acids of lipopolysaccharides as
      well as ether lipids decreased consecutively during the observation period. Total
      microbial abundance was estimated to be (4.1-7.3) x 10(9) cells g(-1) soil (dry
      weight). About 44% account for aerobic and 32% for facultative anaerobic
      bacteria, and 24% for archaea, on average. According to the profile and patterns
      of PLFA in the soil sample, it may be suggested that the paddy soil at the August
      sampling period contained more abundant facultative anaerobic bacteria (ca. 36%)
      and archaea (ca. 37%), but the total microbial biomass was significantly lower
      than in the remaining sampling periods. As the plant approached maturity, the
      microbial community structure in the soil changed to contain more abundant Gram
      negative bacteria and methanotrophs.

PMID- 10882433
TI  - Detection of Methane Oxidizing Bacteria in Forest Soil by Monooxygenase PCR
      Amplification.
AB  - Atmospheric methane oxidation by a spruce forest soil from Norway at 15 degrees C
      was found to be maximal at a depth of ca 7 cm. Examination of the kinetics of
      this methane oxidation revealed an apparent K(m) of 403.1 nM and a V(max) of 2.2
      nmol g(-1) dry weight soil h(-1). The low apparent K(m) suggested the presence of
      active methane oxidizing bacteria with a high affinity for methane. DNA was
      extracted from the 5-10 cm horizon, purified, and subjected to PCR amplification
      with primers directed toward the monooxygenase genes pmoA and amoA, which are
      essential for methane oxidation. Hybridization analysis of the clone library
      subsequently constructed revealed that 49% of the 76 cloned PCR fragments were
      putative methanotroph pmoA sequences and 16% were putative ammonium oxidizing
      nitrifier amoA sequences. Sequencing of 28 clones identified three major groups
      showing homology to pmoA from Methylococcus capsulatus, beta-subdivision ammonia
      oxidizers (amoA), and a new group of monooxygenase pmoA/amoA sequences.

PMID- 10882434
TI  - Horizontal Distribution Patterns of Testate Amoebae (Protozoa) in a Sphagnum
      magellanicum Carpet.
AB  - The distribution of soil microorganisms is generally believed to be patchy and to
      reflect habitat heterogeneity. Despite this general rule, the amount of existing
      data on species distribution patterns is scarce. Testate amoebae (Protozoa;
      Rhizopoda) are an important component of soil microbial communities and are
      increasingly used in ecological and paleoecological studies of Sphagnum-dominated
      peatlands, but data on the spatial structure of communities are completely
      lacking. This is an important aspect since quantitative models used for
      paleoecological reconstruction and monitoring are based on species assemblages.
      We explored the distribution patterns of testate amoebae distribution in a
      macroscopically homogeneous Sphagnum carpet, down to a scale of several
      centimeters. Distributions maps of the species and spatially constrained sample
      groups were produced. Multivariate and individual spatial autocorrelations were
      calculated. The importance of spatial structure was quantified by canonical
      correspondence analysis. Our ultimate goal is to find the finest resolution of
      environmental monitoring using testate amoebae. The distribution patterns
      differed among species, resulting in a complex spatial structure of the species
      assemblage in a whole. Spatial structure accounted for 36% of the total variation
      of species abundance in a canonical correspondence analysis constrained by
      spatial variables. This structure was partly correlated to altitude
      (microtopography) at a very fine scale. These results confirmed the existence of
      significant broad- and fine-scale spatial structures within testate amoebae
      communities that could in part be interpreted as effects of ecological gradients.
      This shows that, on a surface area of 0.25 m(2), ecological conditions which look
      uniform from a macroscopic point of view are not perceived as such by Sphagnum
      inhabiting organisms. Therefore, testate amoebae could prove very useful to
      monitor fine-scale ecological processes or disturbances. Studies of the species'
      spatial distribution patterns in combination with autoecological studies are
      needed and should be included in the toolbox of biomonitoring itself.

PMID- 10882435
TI  - Transport of Wild-Type and Recombinant Nucleopolyhedroviruses by Scavenging and
      Predatory Arthropods.
AB  - Wild-type and recombinant nucleopolyhedroviruses (NPVs) were compared in their
      capability to be transported over limited distances by the predator Podisus
      maculiventris (Say) and scavengers Sarcophaga bullata (Parker) and Acheta
      domesticus (Linnaeus) in Trichoplusia ni (Hubner) larvae infesting collards in a
      greenhouse microcosm. Viruses tested were variants of Autographa californica
      (Speyer) NPV (AcNPV): wild-type virus (AcNPV.WT), AcNPV expressing a scorpion
      toxin (AcNPV.AaIT), and AcNPV expressing juvenile hormone esterase (AcJHE.SG).
      Podisus maculiventris transported AcNPV.WT and S. bullata transported AcNPV.WT
      and AcNPV.AaIT. Prevalence and transport of AcNPV.WT were greater than those of
      AcNPV.AaIT and AcJHE.SG, regardless of whether the nontarget organism carriers
      were present or absent. Podisus maculiventris and S. bullata transported
      recombinant and wild-type NPVs at a rate of up to 62.5 cm/day, and A. domesticus
      transported wild-type NPV at 125 cm/day. The infected host insects, T. ni,
      undoubtedly contributed to viral transport in the current research. In every
      experiment, both the wild-type and recombinant virus spread to some degree in the
      plots without predators or scavengers. The relative amounts of NPVs that
      accumulated in soil, as indicated by bioassay mortality percentages, generally
      exhibited spatial patterns similar to those of T. ni mortality due to NPV on the
      collards plants. Thus, the predator and scavengers in the current research
      demonstrated some capacity to transport wild-type as well as recombinant viruses
      at significant rates in a greenhouse microcosm.

PMID- 10882436
TI  - Bees Scavenge Airborne Bacteria.
AB  - An air conditioned wind tunnel system was designed, fabricated, and tested to
      determine whether tethered bees scavenge microbeads or Bacillus subtilis var.
      niger spores from aerosols. Tests showed that microbeads and spores were
      scavenged by bumblebees and honeybees, respectively. Five independent variables
      and their interactions were used in a stepwise multiple regression. Two of them,
      the cube root of the electrostatic charge on the honeybee and the dose of the
      spore aerosol, accounted for most of the statistically significant fit to the
      model's two dependent variables: the percentage of the dose adsorbed by honeybees
      and the number of spores adsorbed by the same bees. Both dependent variables
      increased directly so that an increase in electrostatic charge on the bee (i.e.,
      cube root 32 pC) resulted in an increase (i.e., approximately 1%) in the spore
      dose adsorbed and the number of spores adsorbed by the bees. It was theorized
      that the spores were in an adsorption/desorption equilibrium that responded to
      the concentration "pressure" of the spore aerosol. Further, the charge on the bee
      affected the adsorption force on the bee's surface, as well as increasing the
      effective aerosol volume accessible for the bee's scavenging. In short, relating
      these findings to bees scavenging bacteria from the ambient atmosphere, it
      appears that the spore exposure (where exposure means the product of the ambient
      concentration, the time the bee is exposed, and air volume through which the bee
      flies) controls the number of spores adsorbed by a bee, and the static charge on
      the bee controls the adsorption/desorption equilibrium and presumably the
      scavenging volume.

PMID- 10882437
TI  - Occurrence and Multiple Antibiotic Resistance Profiles of Non-fermentative Gram
      Negative Microflora in Five Brands of Non-carbonated French Bottled Spring Water.
AB  - Five brands of French bottled mineral water were analyzed by heterotrophic plate
      counts (HPC) and for the presence of multiple antibiotic resistant bacteria. HPC
      at 22 degrees C were around 10(4) colony forming units ml(-1) on R2A medium.
      Enumeration on PCA/10, MH, and especially PCA and King B media was less
      efficient. At 37 degrees C, HPC were two to three orders of magnitude less than
      at 22 degrees C. Moreover, phenotypic diversity (7 to 15 phenotypes) was optimal
      on R2A incubated at 22 degrees C. All isolates were identified as non
      fermentative Gram-negative rods and 75% were non-identifiable with the API 20NE
      system. Stenotrophomonas maltophilia and fluorescent Pseudomonas were isolated on
      VIA and CFC selective agar media, respectively. Burkholderia cepacia strains were
      not isolated on BCSA medium. The species S. maltophilia was found in 33%, 28%,
      and 11% of sample from springs A, D, and E, respectively. Independent of brand,
      isolates from HPC media were less efficient to achieve confluent growth in 18 h
      on MH at 30 or 37 degrees C (0 to 40%) than isolates from selective media (28 to
      63%). Seventy percent of the total isolates from dominant microflora (1-5 x 10(3)
      CFU ml(-1) on HPC media) were resistant against two or four antibiotics. The
      antibiotics concerned were principally aztreonam, ampicillin, and nalidixic acid.
      The remaining dominant bacteria showed a 6-9 multiple antibiotic resistant (MAR)
      pattern. All isolates were susceptible to newer antimicrobial agents. Owing to
      their low nutrient and temperature requirements, these isolates are unlikely to
      cause concern to public heath. Fifty percent of strains isolated from selective
      media (non-dominant microflora, 4-40 CFU l(-1)) showed a 10-18 MAR pattern and
      33%, identified as S. maltophilia, a 20-27 MAR pattern. However, minocycline was
      effective against all isolates. Owing to its low concentration, colonization of
      human intestine by MAR S. maltophilia is unlikely.

PMID- 10882438
TI  - Arthroscopic inferior capsular split and advancement for anterior and inferior
      shoulder instability: technique and results at 2- to 5-year follow-up.
AB  - We present a modification of the arthroscopic Bankart repair that includes an
      inferior capsular split. This technique allows up to 2 cm of additional capsular
      advancement, restoring more normal capsular tension by addressing plastic
      elongation of the capsule. Prospective evaluations of 34 patients with 2- to 5
      year follow-up are included in this report. Average patient age was 25.1 years
      (range, 16 to 40 years). Twenty-two patients had experienced at least 1
      anterior/inferior dislocation. Ten patients had chronic anterior/inferior
      subluxation. Two patients were considered multidirectional. Time from dislocation
      or the duration of symptoms to the repair ranged from 1 month to 13 years. The
      first 5 repairs were performed using transglenoid suture fixation, the last 29
      with suture/anchor technique. There were no neurological complications. The
      average postoperative Bankart score was 91.6 (range, 40-100). In 30 of 34
      patients, there has been no recurrence of subluxation or dislocation. Two of the
      5 transglenoid repairs had a recurrence (40% recurrence rate). Two of 29 patients
      in the suture anchor group had a recurrence (6.9% recurrence rate). We believe
      that the addition of an inferior capsular split, used in conjunction with a
      suture/anchor repair, restores more normal capsular tension and especially
      addresses the inferior component of anterior/inferior shoulder instability. We
      include an inferior capsular split and advancement routinely when performing
      arthroscopic Bankart repairs.

PMID- 10882439
TI  - Multiquadrant digital analysis of shoulder capsular thickness.
AB  - PURPOSE: Nonablative thermal capsular shrinkage has been developed in an attempt
      to address the plastic capsule deformation thought to cause increased rates of
      recurrent instability following arthroscopic stabilization procedures. Although
      the temperature required to optimize collagen shrinkage is known, a safe depth of
      thermal penetration, in various locations about the shoulder capsule, has not
      been defined. The purpose of this study was to measure shoulder capsule thickness
      by quadrant and circumferentially from the glenoid to the humerus so that thermal
      energy in shoulder procedures can be more precisely applied to limit possible
      injury to pericapsular structures. TYPE OF STUDY: This is an anatomic study using
      a cadaveric shoulder specimens. MATERIALS AND METHODS: Soft tissue was dissected
      from 8 fresh cadaveric shoulders to isolate intact glenohumeral joint capsules.
      The humeral insertion was released and the capsule was cut into 6 longitudinal
      quadrants around the glenoid. The capsule specimens were then flash frozen and
      stored at -80 degrees C. Quadrant tissue was cut into longitudinal sections 14 to
      16 microm wide and stained with hematoxylin and eosin. The specimens were then
      digitized under a dissecting microscope and measured using computer imaging
      software at approximately 4-mm intervals. Two-way analysis of variance (ANOVA)
      was performed on the measurements of the intact capsule specimens 2.5 cm off the
      glenoid. Humeral insertion data were recorded separately. RESULTS: A total of 248
      separate measurements were made throughout the capsule in 8 specimens. Capsular
      thickness increased from an average of 2.42 mm anteriorly to 2.80 mm in the
      inferior capsular pouch and again thinned to 2.22 mm posteriorly. Global shoulder
      capsule thickness ranged from 1.32 to 4.47 mm. When analyzed by position, from
      glenoid to humerus, a general thinning was noted with a mean thickness of 3. 03
      mm at the glenoid to 2.17 mm at the humeral insertion. Two-way ANOVA showed a
      significant thickness variation along the specimen (P <.05), a nearly significant
      thickness variation with regard to quadrant (P <.03), and no significant
      interaction (P >.07) when applied to specimen measurements approximately 2.5 cm
      off the glenoid. CONCLUSIONS: The thickness of the shoulder capsule ranges from
      1.32 to 4.47 mm, with a significant thinning laterally from the glenoid to the
      humerus. Further, capsule thickness ranges from 2.76 to 3.18 mm in the regions in
      closest proximity to the axillary nerve. These data may help determine the proper
      amount of thermal penetration necessary when performing shrinkage procedures and
      provide safety guidelines to limit the depth of thermal penetration to avoid
      possible injury to pericapsular structures.

PMID- 10882440
TI  - Arthroscopic transglenoid suture repair for initial anterior shoulder
      dislocation.
AB  - PURPOSE: To evaluate the long-term results after arthroscopic transglenoid suture
      repair for initial anterior shoulder dislocation. TYPE OF SYUDY: Outcome study.
      MATERIALS AND METHODS: Selection for surgery was based on the sporting ambitions
      of the patients and the documentation of instability. Evidence of instability
      included the sonographic documentation of ventral drawer compared with the
      unaffected opposite shoulder as well as instability testing under anesthesia.
      Patients with preoperatively stable shoulder or multidirectional instability
      underwent conservative therapy. All patients underwent surgical repair with a
      transglenoid suture technique, initially using a single drill hole; in recent
      years, however, we have used 2 drill holes placed in the 3 o'clock and 5 o'clock
      positions. Postoperative care was initiated with 4-week immobilization in a
      Gilchrist bandage. Subsequently, physiotherapeutic mobilization was started,
      avoiding rotational movements for the first 3 weeks. In the period between 1988
      and 1995, 72 patients with traumatic first-time dislocation underwent
      arthroscopic stabilization at the Department of Trauma Surgery of the Krankenhaus
      der Barmherzigen Bruder Eisenstadt. The patients included 61 men and 11 women
      with an average age of 27.2 years (range, 19 to 39 years). RESULTS: The clinical
      instability documented showed a significant correlation to the instability found
      under anesthesia that was documented immediately before arthroscopic exploration.
      Arthroscopic exploration revealed a Bankart lesion in 25 cases (34.7%), with a
      small bone fragment found in 6 of these cases. Forty-three patients showed an
      avulsion of the capsulolabral complex displaced medially to the neck of the
      scapula, combined with a bucket-handle lesion of the superior anteroposterior
      labrum in 12 of these cases. Sixty-seven patients (93%) were available for
      clinical follow-up after an median of 66 months (range, 24 to 108 months) with
      patients achieving an average 91.3 points in the Carter-Rowe score. Five of the
      patients (6.9%) (average age, 20.4 years) experienced postoperative redislocation
      after 3 to 11 months being the result of an adequate trauma in 2 of the patients.
      All patients with redislocation had originally presented with a Bankart lesion,
      with medially displaced capsulolabral complex combined with a bucket-handle
      lesion of the proximal labrum in 2 patients. Eighty-five percent of the patients
      have resumed full sporting activity and presently have full load-bearing capacity
      of the operated shoulder. CONCLUSIONS: Compared with the poor results after
      conservative therapy with recurrence rates of up to 90% for young, athletically
      active patients, arthroscopic treatment has been shown to be highly efficient.

PMID- 10882441
TI  - Arthroscopic debridement of the shoulder for osteoarthritis.
AB  - Twenty-five patients underwent arthroscopic debridement to treat early
      glenohumeral osteoarthritis. The group consisted of 19 men and 6 women with an
      average age of 46 years (range, 27 to 72 years.) The operative procedure
      consisted of lavage of the glenohumeral joint, debridement of labral tears and
      chondral lesions, loose body removal, and partial synovectomy and subacromial
      bursectomy. Follow-up averaged 34 months, with a range of 12 to 63 months.
      Overall, results were rated as excellent in 2 patients (8%), good in 19 patients
      (72%), and unsatisfactory in 5 (20%). Two patients had complete relief of pain,
      18 patients had only occasional mild pain, and 5 had moderate to severe pain
      postoperatively. Of the 12 patients with marked preoperative stiffness, 10 (83%)
      had improvement in range of motion postoperatively. Arthroscopic debridement is a
      reasonable approach for treating early glenohumeral osteoarthritis that has
      failed to respond to nonoperative treatment, in which the humeral head and
      glenoid remain concentric, and where there is still a visible joint space on an
      axillary radiograph. The procedure is not recommended when there is severe joint
      incongruity or large osteophytes.

PMID- 10882443
TI  - Flipped patellar tendon autograft anterior cruciate ligament reconstruction.
AB  - To determine the efficacy of an anterior cruciate ligament (ACL) graft that
      customizes length and facilitates anatomic outlet fixation, a prospective study
      of the "flipped" patellar tendon autograft ACL reconstruction began in 1995. This
      technique shortens the tendon portion to match the intra-articular length by
      rotating 1 bone plug 180 degrees proximally onto the tendon, thus flipping the
      bone plug over its ligamentous insertion. Bioscrews (poly L-lactic acid;
      Linvatec, Largo, FL) secured the grafts. All patients undergoing this procedure
      with a minimum 21 months follow-up were reviewed. Preoperative and postoperative
      Tegner, Lysholm, and IKDC activity scores, and Lachman and pivot shift tests were
      obtained. Postoperative KT testing and radiographs were obtained. Fifty patients
      were followed-up for an average of 28 months (range, 21 to 39 months). Average
      patient age was 34 years (range, 16 to 52 years). Tegner scores increased from
      2.0 preoperatively to 6.0 postoperatively. Lysholm scores increased from 46
      preoperatively to 93 at follow-up, with 86% excellent (66%) or good (20%). IKDC
      activity scores increased from 3.1 preoperatively to 1.7 postoperatively. KT
      manual-maximum difference at follow-up averaged 0.7 mm, with 74% less than 3-mm,
      18% 3- to 5-mm, and 8% greater than 5-mm difference. Postoperative Lachman
      results were 0 in 45 patients and 1+ in 5 patients. Postoperative pivot shift was
      absent in all but 1 patient. Full extension was achieved in all cases and flexion
      averaged 136 degrees with no patient having less than 120 degrees flexion. No
      lytic bone changes or tunnel widening were seen. The flipped patellar tendon
      autograft reduces graft length to its intra-articular portion, increasing graft
      stability, isometry, and stiffness, and avoiding tunnel graft mismatch with
      clinically excellent results.

PMID- 10882442
TI  - Preoperative anterior knee laxity did not influence postoperative stability
      restored by anterior cruciate ligament reconstruction.
AB  - Eighty-six chronic anterior cruciate ligament (ACL)-injured patients were
      quantitatively measured for anterior knee stability preoperatively and at 2 years
      or later (mean, 30 months) postoperatively to examine the influence of
      preoperative knee laxity on the postoperative knee stability restored by the ACL
      reconstruction using multiplied hamstring tendon graft. The patients were divided
      into 3 groups according to the preoperative injured minus normal anterior laxity
      difference (AL-D) (group I [n = 27] <5 mm, group II [n = 48] 5 to 9 mm, group III
      [n = 11] >10 mm). The 3 groups were comparable in gender, age, meniscal status,
      graft excursion measured during operation, time from injury to operation, and
      activity level. The postoperative AL-D in group I was 0.8 +/- 1. 7 mm, that in
      group II was 1.1 +/- 1.6 mm, and in group III was 1.5 +/- 1.4 mm. There were no
      significant statistical differences among these 3 groups. With our surgical
      technique including postoperative rehabilitation, patients with severe
      instability could be treated successfully without needing any additional
      procedures such as extra-articular augmentation or specially designed
      postoperative rehabilitation programs.

PMID- 10882444
TI  - Bioabsorbable polyglyconate interference screw fixation in anterior cruciate
      ligament reconstruction: a prospective computed tomography-controlled study.
AB  - PURPOSE: It was the purpose of the study to evaluate a new polyglyconate
      bioabsorbable interference screw for graft fixation in anterior cruciate ligament
      (ACL) reconstruction. TYPE OF STUDY: Prospective randomized. MATERIALS AND
      METHODS: Forty patients who underwent endoscopic ACL reconstruction were included
      in the study and randomized intraoperatively. Group A consisted of 20 patients (6
      women, 14 men; mean age, 29.6 years) who had femoral bone block fixation with a
      bioabsorbable interference screw and tibial fixation with a titanium interference
      screw. Group B included 20 patients (5 women, 15 men; mean age 29.6 years) who
      had fixation of both femoral and tibial bone blocks with titanium interference
      screws. There was no significant difference between the groups with regard to
      age, gender, height, weight, time from injury to surgery, activity level, and
      concomitant injuries. RESULTS: Clinical results (using IKDC, Lysholm, Tegner
      scores) of the 2 groups as well as instrumented laxity measurements (KT-1000) did
      not show significant (P >.05) differences at any stage of follow-up. No
      complications with respect to graft fixation could be found. Computed tomography
      scans, performed within the first postoperative week, at 6 weeks, and at 3, 6,
      12, and 24 months postoperatively revealed a uniform picture for all patients
      within the groups, showing completed screw degradation at 12 months in group A.
      CONCLUSION: Polyglyconate interference screw fixation for patellar tendon grafts
      has not been found to be associated with increased clinical complications or
      significant osteolysis. It provided equivalent fixation and clinical results
      compared with titanium screws. However, replacement of the screw with bone did
      not take place for up to 3 years postoperatively.

PMID- 10882445
TI  - Locating femoral graft placement from lateral radiographs in anterior cruciate
      ligament reconstruction: a comparison of 3 methods of measuring radiographic
      images.
AB  - Graft positioning in anterior cruciate ligament (ACL) reconstruction is usually
      documented from lateral postoperative radiographs. The purpose of this study was
      to compare 3 measurement methods for femoral graft placement in 50 patients with
      ACL reconstruction. Intraoperative radiographic images were obtained and divided
      into 2 groups. The first group showed suboptimal projections, with out-of-plane
      rotations causing the femoral condyles to not be perfectly overlapped. The second
      group showed good projection, with optimal rotation and fully overlapped femoral
      condyles. In our study, only the measurement technique described by Amis produced
      data with the least measurement error when multiple observers assessed both
      groups. It is recommended that Amis' method be used to measure femoral ACL graft
      position so that reliable data are available for comparison between medical
      centers.

PMID- 10882446
TI  - Cyclic testing of meniscal sutures.
AB  - Suturing the meniscus has become a standard procedure for repairable tears.
      Studies investigating the outcome of meniscal sutures report a considerable rate
      of failures. Regarding the indications, which have been extended to the avascular
      zones, and regarding some accelerated rehabilitation protocols, the need for
      further in vitro investigations has become obvious. The aim of this study was to
      compare different meniscal suture types (vertical and horizontal mattress
      sutures) and materials (absorbable monofilament PDS 2-0, and nonabsorbable
      braided Ethibond 2-0 [Ethicon, Somerville, NJ]) under standard and cyclic loading
      conditions. Testing was performed on medial porcine menisci. In group A,
      specimens were tested to failure at a cross-head speed of 50 mm/minute. In group
      B, cyclic testing (100 cycles) was performed first within different load
      intervals (5 to 20 N and 5 to 40 N). Finally, the specimens were loaded until
      failure. In both groups, the failure loads were recorded and the failure modes
      were analyzed. In group A, there was no difference between suture type or suture
      material, with a mean failure load of 60 N. The failure modes were significantly
      different for vertical (100% suture failure) and horizontal sutures (50% suture
      failure) (P <.0001). In group B, 13% of the sutures failed under cyclic loading
      (7 with 40-N load, 1 with 20-N load). The gap of the sutured tear that appeared
      within the first load cycles was broader in horizontal sutures (P <.001). During
      the first cycles, the thread cut through the meniscus tissue and disappeared from
      the surface (partial tissue failure). There was no difference according to suture
      material. The ultimate failure loads after cyclic loading did not differ from the
      values of group A. These results show that meniscal sutures may fail under
      repetitive loading conditions and that a gap appears between the meniscal margins
      within the first loading cycles irrespective of the suture type and suture
      material used. The appearance of the gap and suture disappearance on the meniscal
      surface because of partial tissue failures (which were more pronounced in the
      horizontal sutures) confirmed the superior resistance of meniscal tissue to
      vertical sutures.

PMID- 10882447
TI  - Radiographic knee dimensions in discoid lateral meniscus: comparison with normal
      control.
AB  - We reviewed the knee radiographs of 68 cases of arthroscopically proven discoid
      lateral meniscus, including 42 cases of complete type and 26 cases of incomplete
      type discoid lateral meniscus. Knee radiographs of 70 cases that had no
      arthroscopic evidence of pathology of the meniscus were used as controls. We
      excluded patients who had significant trauma history and who were under 16 years
      of age or over 60 years to avoid measuring radiographs of skeletally immature or
      degenerative knees. The absolute values and relative normalized values of
      specific knee dimensions, such as a squared-off appearance of the lateral femoral
      condyle, widened femorotibial joint space, cupping of the lateral tibial plateau,
      obliquity of the lateral tibial plateau articular surface, high fibular head, and
      hypoplasia of the lateral intercondylar spine, were compared between the patients
      with discoid lateral meniscus and the normal controls. Among those dimensions,
      high fibular head and widened lateral tibiofemoral joint space showed
      statistically significant differences between the discoid lateral meniscus group
      and normal control group. We suggest that these findings would be useful in
      screening lateral discoid meniscus on plain radiography.

PMID- 10882448
TI  - Meniscal allografts: evaluation with magnetic resonance imaging and correlation
      with arthroscopy.
AB  - PURPOSE: To correlate clinical results to magnetic resonance imaging (MRI) and
      arthroscopy after cryopreserved nontissue-antigen-matched meniscal
      transplantations. TYPE OF STUDY: Blinded; the observers were blinded for each
      others' assessment. MATERIALS AND METHODS: Sixteen consecutive patients were
      included in the protocol. First, clinical evaluation and MRI were performed.
      Second, within 24 hours, arthroscopy was performed. RESULTS: The clinical results
      showed better correlation between clinical results and arthroscopy than between
      clinical results and MRI. In the present study, MRI was not beneficial in
      evaluating meniscal transplants. CONCLUSIONS: Using more sophisticated MRI
      techniques, the correlation between clinical results, arthroscopy, and MRI could
      probably be improved.

PMID- 10882449
TI  - Correlation between osteoarthritic cartilage damage and levels of proteinases and
      proteinase inhibitors in synovial fluid from the knee joint.
AB  - Matrix metalloproteinases (MMPs) in the synovial fluid are responsible for
      collagen breakdown during physiologic cartilage turnover and the pathologic
      destruction of the cartilage. We measured the levels of MMPs, specific tissue
      inhibitors of metalloproteinases (TIMPs), and interleukin-6 (IL-6) in synovial
      fluid from the knees of 36 patients with cartilage lesions subdivided according
      to severity based on arthroscopic findings. Lesions were classified as mild
      (group 1, edema with no disruption of the surface), moderate (group 2, open
      lesions without exposure of subchondral bone), or severe (group 3, exposure of
      subchondral bone). Zymography (gel electrophoresis in the presence of
      hydrolizable substrates) showed a 60-kd band in all samples. A second band (94
      kd) was found exclusively in specimens from groups 2 and 3, and a third band (110
      kd) was present only in group 3. Concentrations of 2 of the most important
      modulators of MMP activity, TIMP-1 and IL-6, were measured. TIMP-1 levels did not
      vary significantly with the severity of cartilage damage. Linear regression
      analysis revealed a significant positive correlation between TIMP-1 and IL-6 in
      groups 1 and 2. These data indicate that the severity of the cartilage damage
      corresponds with MMP activity. The correlation between IL-6 and TIMP-1 in groups
      with mild and moderate damage suggests a regulating mechanism that is absent in
      severe lesions.

PMID- 10882450
TI  - The effect of monopolar radiofrequency energy on partial-thickness defects of
      articular cartilage.
AB  - PURPOSE: To evaluate the effect of monopolar radiofrequency (RF) energy on
      partial-thickness defects of articular cartilage, comparing the outcome of
      partial-thickness defects treated with monopolar RF energy with that of treatment
      by conversion of partial-thickness defects to full-thickness defects by curettage
      and microfracture. TYPE OF STUDY: Randomized trial using adult female sheep.
      MATERIALS AND METHODS: Thirty-six sheep were used in this study. Both stifles in
      each animal were randomly assigned to 1 of the following 3 procedures: (1)
      partial-thickness defect without any treatment to serve as a sham-operated
      control, (2) partial-thickness defect with RF energy treatment, and (3) partial
      thickness defect treated by conversion of the defect to a full-thickness defect
      by curettage and microfracture. Nine sheep were euthanized at 0, 2, 12, and 24
      weeks after surgery (n = 6 per group). After euthanasia, cartilage samples were
      harvested from the defect sites, and chondrocyte viability was analyzed by
      confocal laser microscopy using a triple-labeling technique. Cartilage samples
      also were decalcified and stained with hematoxylin and eosin and safranin-O for
      histologic analysis. Surface properties of cartilage samples were analyzed using
      scanning electron microscopy. RESULTS: The analysis of chondrocyte viability
      showed that RF treatment caused death of almost all chondrocytes in the defect.
      Histologic analysis showed that RF treatment caused detrimental effects to
      chondrocytes and proteoglycan concentration that progressed over time, and that
      full-thickness defects were repaired by fibrocartilage by 24 weeks after surgery.
      Scanning electron microscopy analysis indicated that RF-treated groups were
      significantly smoother and less irregular than control groups at 2, 12, and 24
      weeks after surgery. CONCLUSIONS: This study showed that monopolar RF energy
      caused long-term damage to cartilage in this sheep model and did not appear to
      have the beneficial effects reported in a previous study that evaluated
      application of this technique using a bipolar RF probe.

PMID- 10882451
TI  - Arthroscopic removal of os centrale carpi causing wrist pain.
AB  - The os centrale carpi is a relatively rare accessory carpal bone of the wrist
      that infrequently has been reported to cause symptoms. This report describes 2
      cases where an apparently mobile os centrale carpi caused painful clicking and
      crepitus and where the symptoms disappeared after arthroscopic removal of the
      ossicles.

PMID- 10882452
TI  - Hamato-lunate impingement: an uncommon cause of ulnar-sided wrist pain.
AB  - It has been reported that almost 50% of lunates have a separate medial facet on
      the distal surface for articulation with the hamate; about a quarter of these
      have erosion of the cartilage with exposed subchondral bone on the proximal pole
      of the hamate. We describe 4 cases of ulnar-sided wrist pain caused by hamato
      lunate impingement that resulted in chondromalacia. The pain could be reproduced
      by a modification of the Lichtman test. The diagnosis was confirmed by
      arthroscopy. All 4 patients responded favorably to resection of the head of the
      hamate.

PMID- 10882453
TI  - Meniscal repair in very young children.
AB  - This article reports the cases of what we believe to be the youngest patients
      with traumatic meniscal tears treated by repair. The 2 cases were treated with
      different meniscal repair techniques. A review of the literature regarding
      traumatic meniscal tears in children is provided.

PMID- 10882454
TI  - Arthroscopic biceps tenodesis: operative technique.
AB  - Biceps tenodesis is indicated for partial biceps tendon tears or biceps tendon
      subluxation. We present our technique for arthroscopic biceps tenodesis.

PMID- 10882455
TI  - Extra-articular lateral reconstruction technique.
AB  - This article describes an anterolateral reconstruction procedure that, when used
      in combination with an intra-articular anterior cruciate ligament (ACL)
      reconstruction, restores rotary and anterior knee stability. We believe that
      failing to recognize lateral instabilities and to perform an extra-articular
      reconstruction is an under-recognized cause of failure of ACL reconstruction. We
      also describe the indications, medical histories, and physical examination tests
      used to determine when an anterolateral reconstruction is needed. One should
      suspect a compromise of the lateral structures when presented with a failed ACL
      reconstruction in which the tunnels, the graft, and the rehabilitation all seem
      to have been done properly, or when a prior lateral procedure has been attempted
      and failed. In our experience, if a second ACL reconstruction is undertaken
      without the benefit of a lateral reconstruction, it may fail as well.

PMID- 10882456
TI  - Patellar tendon autograft harvesting using a mini vertical incision.
AB  - Patellar tendon autograft is a commonly used graft for anterior cruciate ligament
      reconstruction. Harvesting the patellar tendon graft typically entails using a
      longer incision than other graft options. We describe a technique for harvesting
      bone-patellar tendon-bone autograft using a smaller more cosmetic incision.

PMID- 10882457
TI  - The SMC knot--a new slip knot with locking mechanism.
AB  - A new slip knot for arthroscopic surgery, the SMC knot, is described. By pulling
      the post strand, a self-locking loop is created. By tensioning the loop strand,
      the self-locking loop creates a snug knot without sliding backward. The SMC knot
      is simple and has a low profile. With a nonabsorbable suture, it provides great
      knot security.

PMID- 10882460
TI  - Technical note: double tibial tunnel using quadriceps tendon in anterior cruciate
      ligament reconstruction.
AB  - To avoid complications related to the use of patellar tendon and hamstring
      (semitendinosus and gracilis) tendon and to create a more anatomic
      reconstruction, we present a new technique based on the use of quadriceps tendon
      placed in a single half femoral tunnel and double tibial tunnels. The graft,
      harvested by a central longitudinal incision, possesses the following
      characteristics: (1) a bone plug 20 mm long and 10 mm in diameter; (2) a tendon
      component 7 to 8 cm long, 10 mm wide, and 8 mm thick; and (3) division of the
      tendon longitudinally into 2 bundles while maintaining the patellar insertion.
      Every bundle has a width and thickness of approximately 5 mm and 8 mm,
      respectively. The total length of the graft is 9 to 10 cm. A 10-mm half femoral
      tunnel is drilled through a low anteromedial portal with the knee flexed at 120
      degrees. A suture loop is left in place in the half tunnel. A double tibial
      tunnel is drilled in a convergent manner (from outside to inside) obtaining an
      osseous bridge between the 2 tunnels. Two suture loops are passed trough the
      tibial tunnels and retrieved in a plastic cannula (10 mm) positioned in the
      anteromedial portal to allow the passage of the 2 bundles in the tibial tunnels.
      The suture loop left in the half tunnel permits the transportation of the bone
      plug in the femoral tunnel. Fixation is achieved by an interference screw at the
      femoral side and by 2 absorbable interference screws (1 for each tunnel). The
      advantages of this technique are a more cross-sectional area (80 mm(2)), greater
      bone-tendon interface, and a more anatomic reconstruction. Theoretically, easier
      bone incorporation, decreased windshield wiper and bungee effect, fewer donor
      site problems, and less tunnel enlargement can also be possible.

PMID- 10882461
TI  - Special report: observations on interference screw morphologies.
AB  - Interference screws are frequently used for fixation of anterior cruciate
      ligament grafts. When revision surgery is necessary, it is important for the
      surgeon to recognize variations in interference screw morphology to reduce the
      potential difficulties in screw removal. The purpose of this observational study
      is to review the variety of metallic and nonmetallic absorbable interference
      screws commonly available and to provide a review of their characteristics,
      dimensions available, and the type and size of screwdriver that would be required
      in the event that removal is necessary.

PMID- 10882462
TI  - The science of tissue engineering.
AB  - This article reviews the development of tissue engineering during the last
      decade. The science began to fully develop in association with efforts to combine
      viable cells with biocompatible material. The history and scope of this new field
      are presented. Basic principles of cell biology, materials, and technologies are
      discussed. Future challenges in the field are presented.

PMID- 10882463
TI  - Bone cells and matrices in orthopedic tissue engineering.
AB  - The ability to harvest and manipulate osteogenic cells gives clinicians the
      opportunity to harness capacity of these cells for targeted regeneration and
      repair of skeletal tissues. Further opportunities to optimize use of cells exist
      in the ability to design specialized matrices that act as conductive scaffolds.
      Realization of the full potential of engineered matrix materials and cell-matrix
      composites can provide new solutions to many clinical problems in skeletal
      reconstruction.

PMID- 10882464
TI  - Bone growth factors.
AB  - Osteoblastic culture models, experimental, and clinical models have revealed that
      bone growth factors influence cellular activity. Growth factors including bone
      morphogenetic proteins, transforming growth factor beta, platelet-derived growth
      factor, insulin-like growth factors I and II, and acidic and basic fibroblast
      growth factors, are powerful tools for fracture healing and bone grafting.
      Understanding the role that bone growth factors play in bone repair is necessary
      to apply these factors in a clinical setting.

PMID- 10882465
TI  - Clinical applications of bone graft substitutes.
AB  - Autogenous bone grafting remains the gold standard for osseous reconstruction in
      clinical practice. It is associated with several limitations. The search for an
      alternative bone graft substitute with combined osteoinductive, osteoconductive,
      and osteogenic properties continues. This article highlights the properties of
      the various bone grafting materials currently available and discusses their
      efficacy in clinical practice.

PMID- 10882466
TI  - The use of growth factors in cartilage repair.
AB  - Articular cartilage, which enables smooth gliding of joints during skeletal
      motion, is vulnerable to injuries and degenerative diseases over time. Bone
      growth factors have a role in the preservation of the cartilage matrix. This
      article reviews the potential to treat cartilage damage for bone morphogenetic
      proteins, insulin-like growth factors, hepatocyte growth factor, basic fibroblast
      growth factor, and transforming growth factor beta.

PMID- 10882467
TI  - Tissue engineering meniscus: cells and matrix.
AB  - Tissue engineering, a relatively new field of research, was born as a result of a
      search for solutions to the limited alternatives currently used to replace
      structure and function lost because of failure or loss of tissues throughout the
      body. The field merges advances in cell biology, growth factor therapy, and
      material design. It encourages creation of tissue-engineered menisci for repair
      and replacement therapy and offers a means for developing a better understanding
      of meniscal cell and matrix biology.

PMID- 10882468
TI  - Meniscal injury and repair: clinical status.
AB  - Repair or resection of meniscal injuries is one of the most common operative
      procedures in orthopedics today. A variety of techniques for reconstruction have
      been attempted and experts are still unsure which treatment of meniscal lesions
      is best. This article reviews different techniques of meniscal repair and some
      novel approaches that may be used for treatment of meniscal lesions in the coming
      years.

PMID- 10882469
TI  - Tissue-engineered ligament: cells, matrix, and growth factors.
AB  - Current treatment modalities for anterior cruciate ligament (ACL) tears rely on
      the use of grafts for reconstruction. Treatment can be divided into three
      categories: autografts, allografts, and synthetic graft replacements. The varied
      success rates and associated advantages and disadvantages of each method have
      resulted in controversy as to the best treatment for ACL injuries.

PMID- 10882470
TI  - Current concepts in intervertebral disc restoration.
AB  - A current focus of treatment for degenerative disk disease is the restoration of
      the intervertebral disk. This article summarizes the structure and function of
      the intervertebral disk, the pathogenesis of its degeneration, and the clinical
      relevance of degenerative disk disease. Current literature relating to
      intervertebral disk replacement and regeneration is reviewed.

PMID- 10882471
TI  - Advances and strategies for spinal cord regeneration.
AB  - Although a cure for spinal cord injuries does not currently exist, advances have
      been made in the field of spinal cord regeneration. This article discusses the
      pathophysiology of spinal cord injury, animal models, and strategies for
      restoration and regeneration of the spinal cord.

PMID- 10882472
TI  - Gene therapy for spine fusion.
AB  - Gene therapy is a novel therapeutic modality for repair and regeneration of
      musculoskeletal tissues, including the spine. Various methods for therapeutic
      gene transfer are presented in this article. Several studies in which gene
      transfer has been used specifically to enhance spine fusion in animal models are
      reviewed.

PMID- 10882473
TI  - Engineering strategies for peripheral nerve repair.
AB  - Tissue engineering in the peripheral nervous system unites efforts by physicians,
      engineers, and biologists to create either natural or synthetic tubular nerve
      guidance channels as alternatives to nerve autografts for the repair of
      peripheral nerve defects. Guidance channels help direct axons sprouting from the
      regenerating nerve end, provide a conduit for diffusion of neurotropic and
      neurotrophic factors secreted by the damaged nerve stumps, and minimize
      infiltration of fibrous tissue. In addition to efforts to control these physical
      characteristics of nerve guidance channels, researchers are optimizing the
      incorporation of biologic factors and engineering interactive biomaterial that
      can specifically stimulate the regeneration process. Current and future research
      will ultimately result in biologically active and interactive nerve guidance
      channels that can support and enhance peripheral nerve regeneration over longer,
      more clinically relevant defect lengths.

PMID- 10882474
TI  - Expansion of hematopoietic stem cells in vitro as a model system for human tissue
      engineering.
AB  - The authors have taken a new approach to finding optimal conditions for
      stimulating conservative division of single isolated CD34(+)lin(-) hematopoietic
      stem cell candidates from human umbilical cord blood. The approach required the
      design and development of a novel multi-well single cell combinatorial culture
      system. This system incorporates the use of a multi-well tissue culture plate in
      which each well receives a single hematopoietic stem cell candidate. During an
      experiment lasting several days to weeks, each cell-containing well is moved
      sequentially and serially to a microscopic imaging system. This movement is
      facilitated by computer control of a motorized stage and stabilization of the
      experiment in an environmentally controlled Biobox built on the microscopic
      stage. New image analysis software facilitates tracking of cell movement,
      recording the time of cell division, and immunophenotyping of multiple,
      individual, or recently doubled cells in real time by a robotically controlled
      pipetting station. The principles of single cell culture should help solve many
      problems in human hematopoietic stem cell expansion and may be applicable to a
      wide range of other systems of interest in tissue engineering.

PMID- 10882476
TI  - Phonological sensitivity and the acquisition of new words in children.
AB  - Two studies are reported which aimed to examine the relationship between
      phonological sensitivity and the acquisition of new words that systematically
      differed in the familiarity of their sound structures. In the first study
      measures of phonological sensitivity, phonological short-term memory, vocabulary,
      and nonverbal ability were administered to forty-one 5-year-old children.
      Phonological sensitivity was related to the paired-associate learning of
      phonologically unfamiliar words, but not to the learning of familiar words. In
      the second study a group of 14 nonreading 5-year-old children received
      phonological sensitivity training. A control group was trained in semantic
      categorization. After the training, the phonological sensitivity group did
      perform better on measures of letter knowledge and phonological sensitivity
      (rhyme and first-sound categorization) and appeared to learn phonologically
      unfamiliar words more easily. The findings of both studies suggest that
      phonological sensitivity can support the acquisition of novel words.

PMID- 10882475
TI  - Competition in early exogenous orienting between 7 and 21 weeks.
AB  - Exogenous (stimulus-driven) orienting between 7 and 21 weeks of age was examined
      in 2 experiments using a display with multiple potential targets of attention. On
      each trial a small moving probe was used to draw attention to one side of the
      display or the other. This moving probe appeared simultaneously with 27 static
      bars. In the first experiment, sensitivity to the moving target was affected
      significantly by the spatial distribution of these red and green static bars for
      14-week-olds but not for 8-week-olds. Sensitivity to the moving target was lower
      for 14-week-olds when most of the red bars appeared contralaterally to the moving
      target. This effect replicated a similar effect observed in J. L. Dannemiller
      (1998). The lack of a contralateral competition effect in Experiment 1 for the 8
      week-olds may have occurred because I used a stronger motion stimulus for the
      younger infants in an attempt to hold the overall performance constant at the 2
      ages. A second experiment using a weaker motion stimulus showed that this
      contralateral competition effect was observable over the entire age range from 7
      to 21 weeks of age. Thus as early as 7 weeks of age, sensitivity for a small
      moving stimulus can be significantly influenced by the simultaneous presence of
      competing targets of attention in the visual field. Large increases in overall
      sensitivity were also found across the age range from 7 to 21 weeks. Results are
      discussed in terms of the development of putative competition mechanisms involved
      in exogenous orienting.

PMID- 10882477
TI  - Effects of teacher feedback on the reputations and peer perceptions of children
      with behavior problems.
AB  - We explored whether teacher feedback modified children's preferences and
      perceptions of a target child with behavior problems. First- and second-grade
      children (M age = 7.8 years) viewed a videotape of a target actor presented as
      having a liked, average, or disliked reputation. A second videotape depicted a
      teacher's verbal responses to the target's behavior as (a) positive, (b) neutral
      salient, or (c) corrective. Both salience and valence of teacher feedback were
      assessed. Main effects of feedback and reputation indicated that feedback had at
      least minimal effects at each level of the target's reputation. Teacher feedback
      is discussed with respect to its effects on perceptions of behavior versus
      affective responses toward behavior-problem children. A significant interaction
      showed that when combined with a liked reputation, positive and neutral-salient
      feedback conditions increased the salience and positive evaluation of the target
      child, thus illustrating the importance of considering nonevaluative teacher
      attention in combination with children's reputational status.

PMID- 10882478
TI  - Genetically perpetuated human neural stem cells engraft and differentiate into
      the adult mammalian brain.
AB  - Human neural stem cells (HNSCs) may serve as a cellular vehicle for molecular
      therapies as well as for cell replacement in the human CNS. The survival,
      integration, and differentiation of HNSC.100, a multipotent cell line of HNSCs
      (A. Villa et al. (2000), Exp. Neurol. 161, 67-84), conditionally perpetuated by
      genetic and epigenetic means, was investigated after transplantation to the
      striatum and substantia nigra of the adult, intact rat brain. These are two key
      regions in the mammalian brain involved in the control of voluntary movement and
      motor coordination, among other functions. Soon after transplantation (1 week),
      the cells had already integrated in a nondisruptive manner into the surrounding
      tissue and migrated out of the implantation site to different distances depending
      on graft location (in the range of 0.5-2.5 mm). Cell migration was markedly more
      extensive in the striatum, where the cells colonized the whole extent of the
      caudate-putamen, than in the substantia nigra region. The engrafted cells
      completely downregulated the stem cell marker nestin and, due to their
      multipotential nature, differentiated and expressed mature neural markers. As
      expected from cells grafted into nonneurogenic regions of the intact brain, the
      majority of differentiated cells expressed GFAP (astroglia), but expression of
      other markers, like GalC (oligodendroglia) and MAP2, beta-tubulin III, NeuN, and
      NSE (for mature neurons) could also be detected. These results demonstrate that
      genetically perpetuated HNSCs, once transplanted, find residence in the host
      brain, where they differentiate, generating mature neural cells in the host,
      chimeric, adult mammalian brain. HNSCs cell lines may be a highly useful model
      for the development of humanized systems for cell replacement and/or gene
      transfer to the CNS, which will likely be strong candidates for future
      therapeutic application in human neurodegenerative conditions.

PMID- 10882479
TI  - Role of the target in the pathfinding of facial visceral motor axons.
AB  - Axon navigation depends, in part, on guidance cues emanating from the target. We
      have investigated the possible role of the target in the pathfinding of visceral
      motor axons to cranial parasympathetic ganglia. Mice homozygous for a tau-LacZ
      transgene targeted in the Phox2a locus lack the sphenopalatine ganglion, which is
      the normal target of visceral motor axons of the facial nerve. We found that in
      these mutants, facial visceral motor axon pathfinding was disrupted, and some
      axons were misrouted to an alternative parasympathetic ganglion. Moreover, the
      absence of correct facial visceral motor pathways was concomitant with defects in
      the pathfinding of rostrally-projecting sympathetic axons.

PMID- 10882480
TI  - Absence of GAP-43 can protect neurons from death.
AB  - The main function of GAP-43 is thought to be regulating growth cone motility and
      axon guidance signals. GAP-43 is highly expressed during development and in
      regenerating nerves and in particular regions of the adult brain. We here present
      the first evidence that GAP-43 can modulate guidance signals emanating from
      Semaphorin III (SemaIII) in cultured NGF-dependent sensory neurons. We further
      show that absence of GAP-43 dramatically increases resistance of specific sensory
      neurons to apoptotic stimuli in vitro. NGF-dependent sensory neurons from GAP-43
      (+/-) and null mutant mice are strongly protected against SemaIII-induced death.
      Furthermore, NGF- and BDNF-dependent neurons, but not NT-3-dependent neurons,
      from GAP-43 null mutant mice are much more resistant to apoptosis induced by
      trophic factor deprivation. We also show that early postnatal Purkinje cells from
      GAP-43 (+/-) mice are more resistant to cell death in organotypic cultures. We
      conclude that GAP-43 can influence neuronal survival and modulate repulsive axon
      guidance signals.

PMID- 10882481
TI  - Long-range interactions in neuronal gene expression: evidence from gene targeting
      in the GABA(A) receptor beta2-alpha6-alpha1-gamma2 subunit gene cluster.
AB  - Clustering of GABA(A) receptor alpha1, alpha6, beta2, and gamma2 subunit genes on
      mouse chromosome 11/human chromosome 5 may have functional significance for
      coordinating expression patterns, but until now there has been no evidence for
      cross-talk between the genes. However, altering the structure of the alpha6 gene,
      specifically expressed in the cerebellum, with neomycin gene insertions in two
      different experiments unexpectedly reduced the expression of the widespread
      alpha1 and beta2 genes in the forebrain. There were corresponding reductions in
      the levels of alpha1 and beta2 subunit proteins and in autoradiographic ligand
      binding densities to GABA(A) receptors in the forebrain of alpha6-/- mice. The
      gamma2 mRNA level was not changed, nor were beta3 and delta mRNAs. The data
      suggest that elements in the neo gene may have an influence over long distances
      in the GABA(A) subunit gene complex on as yet undefined structures coordinating
      the expression of the alpha1 and beta2 genes.

PMID- 10882482
TI  - Regionally distinct regulation of astroglial neurotransmitter receptors by
      fibroblast growth factor-2.
AB  - Fibroblast growth factor (FGF)-2 is an abundant astroglial cytokine. We have
      previously shown that FGF-2 downregulates gap junctions in primary astroglial
      cultures (B. Reuss et al., 1998, Glia 22, 19-30). We demonstrate now that FGF-2
      induces astroglial dopamine (DA) sensitivity and D1 dopamine-receptor (D1DR)
      antigen and message in cortical and striatal astroglial cultures. On the
      functional level 10 micromol/L DA triggered transient increases in astroglial
      [Ca(2+)](i). In gap-junction-coupled cells, no FGF-2-dependent changes in
      proportions of DA-responsive cells were observable. However, uncoupling with
      octanol or 18alpha-glycirrhetinic acid isolated the smaller population of
      astrocytes intrinsically sensitive to DA which was significantly increased by FGF
      2 in cortical and striatal cultures. Administration of DR-specific substances
      revealed that FGF-2 upregulated D1DR. These results indicate that downregulation
      of astroglial gap junctions by FGF-2 is accompanied by an upregulation of D1DR
      and DA sensitivity, adding a new aspect to the role of FGF-2 in the regulation of
      brain functions.

PMID- 10882483
TI  - Cloning and functional expression of rat eag2, a new member of the ether-a-go-go
      family of potassium channels and comparison of its distribution with that of
      eag1.
AB  - A second mammalian gene for the ether-a-go-go (eag) potassium channel has been
      cloned from the rat, and its predicted protein sequence is 70% identical to that
      of rat ether-a-go-go1 with a further 10% conservatively replaced residues. The
      rat eag2 mRNA was predominantly expressed in neural tissue and was not detected
      in adult skeletal, cardiac, or smooth muscle. Within the brain, its distribution
      overlaps that of rat ether-a-go-go1 in specific regions within the cortex and
      olfactory bulb, but was differentially distributed in other locations, being
      scanty within the cerebellum, and most notably present in the thalamus, inferior
      colliculus, and certain brainstem nuclei. Heterologous expression of rat eag2 in
      HEK-293 cells gave rise to a voltage-gated, noninactivating potassium current,
      active at the cells' resting potential and blocked by low nanomolar
      concentrations of cytosolic calcium. Thus, in neurones, this current is likely to
      impart a modulation in membrane conductance, which is sensitively responsive to
      resting internal calcium, and levels of electrical activity.

PMID- 10882484
TI  - Expression of CHL1 and L1 by neurons and glia following sciatic nerve and dorsal
      root injury.
AB  - Cell adhesion molecules (CAMs), particularly L1, are important for axonal growth
      on Schwann cells in vitro. We have used in situ hybridization to study the
      expression of mRNAs for L1 and its close homologue CHL1, by neurons regenerating
      their axons in vivo, and have compared CAM expression with that of GAP-43. Adult
      rat sciatic nerves were crushed (allowing functional regeneration), or cut and
      ligated to maintain axonal sprouting but prevent reconnection with targets. In
      other animals lumbar dorsal roots were transected to produce slow regeneration of
      the central axons of sensory neurons. In unoperated animals L1 and CHL1 mRNAs
      were expressed at moderate levels by small- to medium-sized sensory neurons and
      L1 mRNA was expressed at moderate levels by motor neurons. Many large sensory
      neurons expressed neither L1 nor CHL1 mRNAs and motor neurons expressed little or
      no CHL1 mRNA. Neither motor nor sensory neurons showed any obvious upregulation
      of L1 mRNA after axotomy. Increased CHL1 mRNA was found in motor neurons and
      small- to medium-sized sensory neurons 3 days to 2 weeks following sciatic nerve
      crush, declining toward control levels by 5 weeks when regeneration was complete.
      Cut and ligation injuries caused a prolonged upregulation of CHL1 mRNA (and GAP
      43 mRNA), indicating that reconnection with target tissues may be required to
      signal the return to control levels. Large sensory neurons did not upregulate
      CHL1 mRNA after axotomy and thus regenerated within the sciatic nerve without
      producing CHL1 or L1. Dorsal root injuries caused a modest, slow upregulation of
      CHL1 mRNA by some sensory neurons. CHL1 mRNA was also upregulated by many
      presumptive Schwann cells in injured nerves and by some satellite cells around
      large sensory neurons after sciatic nerve injuries and was transiently
      upregulated by some astrocytes in the degenerating dorsal columns after dorsal
      rhizotomy.

PMID- 10882485
TI  - Measurement of Contact Angles for Fumed Silica Nanospheres Using Enthalpy of
      Immersion Data.
AB  - The hydrophobicity of fine particles is important for their behavior at
      interfaces, for example, in stabilizing emulsions. In this study, contact angles
      were evaluated for silanized fumed silica nanospheres with mean primary diameter
      of about 12 nm, using heat flow microcalorimetry. Three systems were
      investigated: water-air-nanospheres, toluene-air-nanospheres, and toluene-water
      nanospheres. For the water-air-nanospheres system, n-propanol at various
      concentrations in water was used to aid in dispersing the nanospheres, and the
      enthalpy of immersion between water, air, and nanospheres was obtained by
      extraploting to zero n-propanol concentration. Measurements of enthalpy of
      immersion for toluene-air-nanospheres system were straightforward, as all the
      nanospheres samples were dispersible in toluene. The enthalpy of immersion for
      toluene-water-nanospheres system was calculated from the data for the
      aforementioned first and the second systems. For water-air-nanosphere systems,
      contact angles were in the range of 14 to 118 degrees, corresponding to enthalpy
      of immersion from -0.0905 to 0.0041 J/m(2). For the case of toluene-air
      nanospheres systems, the contact angles varied from 72 to 94 degrees with
      corresponding enthalpy of immersion from -0.0295 to -0.0189 J/m(2). For toluene
      water-nanospheres systems, however, contact angles were in the range of 0 to 96
      degrees, corresponding to enthalpy of immersion from -0.0717 to -0.0175 J/m(2).
      Copyright 2000 Academic Press.

PMID- 10882486
TI  - The Primary Electroviscous Effect: Thin Double Layers (akappa>>1) and a Stern
      Layer.
AB  - The primary electroviscous effect due to the charge clouds surrounding spherical
      charged particles suspended in an electrolyte was studied by Hinch and Sherwood
      (J. Fluid Mech. 132, 337 (1983)) in the limit of double layers thin compared to
      the particle radius a. Here we introduce the effect of a dynamic Stern layer into
      that analysis, in order to explain the numerical results of Rubio-Hernandez et
      al. (J. Colloid Interface Sci. 206, 334 (1998)) in terms of the ratio of the
      tangential ionic fluxes within the charge cloud to those within the Stern layer.
      The predictions of the asymptotic analysis are compared with those of numerical
      computations. The thickness of the charge cloud is characterized by the Debye
      length kappa(-1). If akappa>10 the predictions of the asymptotic analysis exhibit
      the same qualitative behavior as the numerical results, but akappa>1000 is
      required to achieve quantitative agreement to within 2.5%. Copyright 2000
      Academic Press.

PMID- 10882487
TI  - Latex Particle Size Distribution by Dynamic Light Scattering: Computer Evaluation
      of Two Alternative Calculation Paths.
AB  - Two calculation paths for estimating the particle size distribution (PSD) of a
      polymer latex from single-angle dynamic light scattering (DLS) measurements are
      evaluated on the basis of a numerical example. In the more common "double-step
      method," two calculation steps are applied, with the intermediate estimation of
      the particle light intensity distribution (PLID). In the "single-step method,"
      the calculation is performed in one operation. From the specification of several
      PSDs, a mathematical model is used to produce the synthetic measurements. An
      iterative procedure was applied for determining the diameter range and the number
      of PSD points. The inversion operations were carried out using a regularization
      technique. For narrow distributions with diameters in the range 100-1000 nm, the
      PSD and the PLID are similar in shape, and both calculation paths produce similar
      results. For broad PSDs in the range 100-1000 nm, and for arbitrary PSDs in the
      range 10-100 nm (i.e., in the Rayleigh region), the single-step method proved
      preferable. Copyright 2000 Academic Press.

PMID- 10882488
TI  - Effect of Interfacial Alcohol Concentrations on Oil Solubilization by Sodium
      Dodecyl Sulfate Micelles.
AB  - Alcohol partitioning and its effect on oil solubilization in Winsor Type I
      microemulsion systems was investigated. The microemulsion systems consisted of
      sodium dodecyl sulfate (SDS), pentanol, isopropanol (IPA), and dodecane, with
      either deionized water or an aqueous solution of 50 mM CaCl(2). Alcohol
      partitioning between aqueous, oil, and interfacial phases of the microemulsion
      was described using a pseudophase model in which the alcohol was assumed to self
      associate in the oil phase. Partitioning in these miroemulsions was consistent
      with pentanol self-association in the oil phase. IPA did not self-associate but
      co-associated with pentanol in the oil phase. IPA concentrations as high as 20
      g/kg of water had no effect on pentanol partitioning. The partition coefficient
      for pentanol between aqueous and interfacial phases was about 220 on a mole
      fraction basis. However, pentanol saturated the interfacial phase at a mole ratio
      of 3 : 1 pentanol to SDS. Addition of pentanol beyond that sufficient to saturate
      the interface resulted in large amounts of pentanol partitioning into the oil,
      reaching concentrations in excess of 25 g dL(-1) of oil phase. Dodecane
      solubilization increased linearly with pentanol mole fraction in the interface up
      to the 3 : 1 pentanol-to-SDS saturation level. The fact that dodecane
      solubilization was unaffected by pentanol at concentrations beyond those
      necessary for interfacial saturation suggests that pentanol behaves as a
      cosurfactant and not a cosolvent in these microemulsion systems. Copyright 2000
      Academic Press.

PMID- 10882489
TI  - Surface and Texture Characterization of Alumina-Supported Copper and Mixed Copper
      Manganese Oxide Catalysts and Their Formate Precursors.
AB  - Alumina-supported copper and copper-manganese oxide catalysts as well as the
      parent formates were characterized by means of FTIR spectroscopy in situ and
      nitrogen physisorption. The IR spectroscopic results are discussed on the basis
      of the deposition scheme proposed recently by Kapteijn et al. (J. Catal. 150, 94
      (1994). The infrared bands in the high-frequency region (OH stretches) indicate
      that the aqueous copper species formed in the solutions are deposited on the
      basic and neutral surface OH groups, while as our previous studies show the
      aqueous manganese species are deposited on the basic and acidic OH groups.
      However, the aqueous manganese species are deposited on the basic and neutral OH
      groups in the presence of copper ions (pH 4.6-4.7). The deposition of the aqueous
      metal species on the protonated basic OH groups occurs as a result of the "ion
      pairing" process. The driving forces resulting in the deposition of the aqueous
      metal species on the neutral OH groups are considered to be hydrogen bonds. The
      deposition of the formate ions is also discussed. The higher uptake of copper as
      compared to manganese is discussed in terms of the metal ion properties
      (electronic configuration, the ability to form hydrogen bonds of different
      strength, metal species-support interaction). The nitrogen physisorption shows
      that the initial mesoporous character of gamma-Al(2)O(3) structure does not
      change during impregnation. The r(FHH) values which characterized the adsorbent
      adsorbate interaction forces are calculated. The comparative analysis of the pore
      size distribution curves of the oxide-supported samples and their parent formates
      proves to be a useful tool to elucidate the metal species-support interaction
      strength. Copyright 2000 Academic Press.

PMID- 10882490
TI  - Light and Oxygen Protective Properties of Materials Induced by Surfactant
      Molecular Complex Formation.
AB  - Crystalline surfactant molecular complexes, the quite stable existence of which
      we firmly established through X-ray structural analysis, etc., were examined with
      respect to the protection from UV light and oxygen provided to their additive
      components. Structural analysis has revealed that the complex additives are
      stably occluded in the mother surfactant crystal matrix. Through the examination
      it was confirmed that additive components in a cationic complex crystal structure
      were perfectly protected from both UV light and oxygen. On the other hand, in
      anionics the additives were perfectly safe from UV attack, but from oxygen the
      change was rather accelerated in comparison with the effect of that on the pure
      condition. Copyright 2000 Academic Press.

PMID- 10882491
TI  - A Study of Surface Properties of Red Mud by Potentiometric Method.
AB  - A bauxite waste of alumina manifacture, i.e., red mud (RM), is an oxide-like
      adsorbent capable of removing radiocesium and strontium. The adsorption behavior
      of these radionuclides is dominated by the surface charge of the adsorbent and
      the number of available adsorption sites. In this study, the surface charge
      densities (sigma), microscopic acidity constants (pK(s)), and site distributions
      of the RM in 10(-3)-1 M concentrations of NaCl, CsCl, and SrCl(2) solutions were
      evaluated from potentiometric titration data. The reciprocal slopes of the pH
      sigma curves are higher than those predicted by double-layer theory. This
      suggests that surface charge and the counter charge are located in a region
      inside the surface because the porous and/or gel surface layer is permeable to
      these ions. Ionic strength dependency of sigma in CsCl solutions is similar to
      those found for other oxides. In SrCl(2) and NaCl solutions, at any pH the
      surface charge decreases as the electrolyte concentration increases. This
      behavior of the RM may be attributed to the existence of differently charged
      oxide surface sites of variable affinity for electrolyte ions. Uptake of protons
      on these sites could be interpreted in terms of H(+) adsorption and well
      described by the Freundlich equation. The empirical Freundlich parameters were
      used to characterize a site distribution function which provides information
      about the affinity ratio of the adsorption sites to H(+) and supporting
      electrolyte cations. Copyright 2000 Academic Press.

PMID- 10882492
TI  - Ethyleneimine Anchored on Thiol-Modified Silica Gel Surface-Adsorption of
      Divalent Cations and Calorimetric Data.
AB  - Activated silica gel was previously modified by the silylant agent 3
      mercaptopropyltrimethoxysilane. The organofunctionalized silica gel containing
      pendant groups ended with the -SH functions reacted with the three-member cyclic
      ethyleneimine molecules to yield the new ligand attaching sulfur and nitrogen
      basic centers available to complex cations. This final anchored surface adsorbs
      MX(2) (M=Co(2+), Ni(2+), Cu(2+), and X=Cl(-), NO(3)(-)) at 298+/-1 K. A
      considerable increase in adsorption capacity was observed for nitrate
      counteranions. This process of extraction was followed by the batch method and
      the order of the maximum capacities found was Ni(2+)>Cu(2+)>Co(2+) for both
      series of salts. The pendant immobilized groups-cation interaction processes
      showed exothermic enthalpies. Those values are more pronounced for chlorides,
      with the largest values obtained for cobalt. The calculated DeltaG values are in
      agreement with the spontaneity of the proposed reactions and the complexation is
      entropically favored. Copyright 2000 Academic Press.

PMID- 10882493
TI  - Water-in-Hydrocarbon Emulsions Stabilized by Asphaltenes at Low Concentrations.
AB  - The role of Athabasca asphaltene particles and molecules in stabilizing emulsions
      was examined by measuring the surface area of water-in-toluene/hexane emulsions
      stabilized by various asphaltene fractions, each with a different proportion of
      soluble and insoluble asphaltenes. The stabilized interfacial area was found to
      depend only on the amount of soluble asphaltenes. Furthermore, the amount of
      asphaltenes on the interface was consistent with molecular monolayer coverage.
      Hence, at low concentrations, asphaltenes appear to both act as a molecular
      surfactant and stabilize emulsions. The effect of the hexane : toluene ratio on
      emulsion stability was examined as well. At lower hexane : toluene ratios, more
      asphaltenes were soluble but the surface activity of a given asphaltene molecule
      was reduced. The two effects oppose each other but, in general, a smaller
      fraction of asphaltenes appeared to stabilize emulsions at lower hexane : toluene
      ratios. The results imply that the emulsifying capacity of asphaltenes is reduced
      but not eliminated in better solvents. Copyright 2000 Academic Press.

PMID- 10882494
TI  - Vapor Nucleation and Droplet Growth: Cluster Distribution Kinetics for Open and
      Closed Systems.
AB  - A theory based on cluster distribution kinetics for single-monomer addition and
      dissociation is presented as a framework for homogeneous and heterogeneous vapor
      nucleation and growth dynamics. For continuous cluster and monomer distributions
      in a well-mixed non-steady-state flow system, population (mass) balance equations
      yield moment equations for the cluster mass moments. Nuclei are either
      homogeneously generated or heterogeneously seeded, and subsequent cluster growth
      occurs by reversible condensation of vapor monomers. The zeroth moment is the
      number (or moles) of clusters, the first moment is cluster mass, and the second
      moment gives cluster-size variance. Solutions are proposed for steady-state flow
      (open) and non-steady-state batch (closed) systems. Experimental data are
      interpreted by recognizing that droplets typically observed in nucleation
      experiments have grown much larger than their nuclei. This allows resolution of
      the large temperature-dependent discrepancy between experiment and classical
      nucleation theory. Copyright 2000 Academic Press.

PMID- 10882495
TI  - Electrosteric Stabilization of Al(2)O(3), ZrO(2), and 3Y-ZrO(2) Suspensions:
      Effect of Dissociation and Type of Polyelectrolyte.
AB  - The mechanisms of eight anionic polyelectrolytes stabilizing colloidal sized
      alpha-Al(2)O(3), pure ZrO(2), and Y(2)O(3)-doped ZrO(2) particles in aqueous
      solution are discussed. The polyelectrolytes studied were the Na(+) and NH(4)(+)
      salts of polyacrylic acid and polymethacrylic acid having different molecular
      weights. The particle-dispersant interactions were studied by measuring
      adsorption isotherms, particle size, thickness of adsorbed layer, and zeta
      potentials by elektrokinetic sonic analysis at different powder volume fractions
      (straight phi=0.01-0.3), pH, and electrolyte (KCl) content. The dissociation of
      the polyelectrolytes was studied by potentiometric titrations. The dissociation
      constant of the polymethacrylates was found to be 0.6 pH unit higher than that
      for the polyacrylates. High-affinity adsorption isotherms were observed over the
      pH range when the polyelectrolytes were fully ionized. The results show good
      correlation between adsorption isotherms and zeta potential data in systems of
      dispersed, dilute alumina particles. When particles and polymers were of equal
      charge (the same sign of charge) the polymer shell was thicker. At higher volume
      fractions (straight phi=0.3), and when alumina particles/added ammonium
      polyelectrolyte were of equal charge, a maximum in the absolute value of zeta
      potential resulted. Due to adsorption all the anionic polyelectrolytes studied
      provided electrosteric stabilization of the alpha-Al(2)O(3), and Y(2)O(3)-doped
      ZrO(2) suspensions by enhancing the zeta potential to 40 mV or over and by
      shifting the isoelectric point to lower pH, the low-molecular-weight
      polyelectrolytes decreasing the isoelectric point more than the polyelectrolytes
      having higher molecular weight. The polyelectrolytes studied failed to stabilize
      pure monoclinic ZrO(2) particles. Due to the shortness of the chain of
      polyelectrolytes studied, no bridging was observed between oppositely charged
      polyelectrolyte/alumina particles. Copyright 2000 Academic Press.

PMID- 10882496
TI  - Phosphatidylserine/Cholesterol Bilayers Supported on a Polycation/Alkylthiol
      Layer Pair.
AB  - 1-Stearoyl-2-oleoyl phosphatidylserine (SOPS)/cholesterol bilayers, supported on
      a polycation/alkylthiol layer pair on a gold surface, were investigated by
      surface plasmon resonance (SPR) and fluorescence recovery after photobleaching.
      The substrate was formed by electrostatic adsorbance of a hydrated
      poly(diallyldimethylammonium chloride) (PDDA) layer on the negatively charged
      surface of a self-assembled monolayer of 11-mercaptoundecanoic acid (MUA) on
      gold. Lipid membranes with different SOPS/cholesterol compositions were deposited
      on the PDDA/MUA layer pair by vesicle fusion. When the cholesterol content was
      below 20%, single bilayers were deposited. Fluorescence recovery after the
      bleaching experiments revealed that the SOPS/cholesterol bilayers were mobile at
      room temperature; lateral diffusion coefficients of a fluorescence probe were
      approximately 1x10(-9) cm(2)/s. The kinetics of the addition of the ion-channel
      forming peptide gramicidin to the supported bilayers was detected by SPR.
      Copyright 2000 Academic Press.

PMID- 10882497
TI  - Studies on Surface Free Energy of an Anhydride-Epoxy Cured System: Effect of Side
      Alkenyl Chain Length of Hardener on Tensile and Impact Properties.
AB  - Three kinds of alkenyl succinic anhydrides (ASA) with varying side chain lengths
      (2-octenyl, 2-dodecyl, and 2-hexadecynyl succinic anhydrides) for hardeners as
      epoxy curing agents are synthesized by the ene reaction. The curing effect of ASA
      on the mechanical tensile and impact properties of cured diglycidyl ether of
      bisphenol-A (DGEBA) epoxy resin is studied. It is observed that increasing the
      side alkenyl chain length of ASA leads to a decrease of tensile strength of the
      cured epoxy resin, probably due to the decreasing of cross-linking density.
      However, it is found that the impact properties of the casting specimens are
      increased as the side alkenyl chain length of the hardener increases. This is
      probably due to the effect of the nonpolar or London-dispersive component of the
      surface free energy of the ASA studied, resulting in improving of the toughness
      properties of the casting specimens. Copyright 2000 Academic Press.

PMID- 10882498
TI  - Dynamics of the Electric Double Layer: Analysis in the Frequency and Time
      Domains.
AB  - No rigorous theory of electrokinetic phenomena is conceivable without properly
      accounting for double layer polarization under the action of external fields.
      Since processes leading to such polarization need a finite time to develop, an
      analysis of the behavior of the quantities of interest (potential and ion
      concentration profiles, particle or fluid velocity, and so on) as a function of
      time should be extremely illustrative. In this work, we analyze how those
      quantities evolve in the nanosecond to microsecond time range after the
      application of an electric field. The network method is proposed (in which,
      essentially, an electric circuit simulator program is used to solve the
      differential equations involved, after their proper interpretation in terms of
      fluxes and forces) to gain information about the evolution with time of the
      potential, counterion, and co-ion perturbations, the particle velocity, and the
      fluid velocity profile. The performance of the method is first ckecked in the
      frequency domain, for which rigorous solutions exist, and then the procedure is
      used in the time domain. Reasons are discussed for the observed time dependencies
      of the analyzed quantities. Copyright 2000 Academic Press.

PMID- 10882499
TI  - Association of Molybdenum Ionic Species with Alumina Surface.
AB  - The adsorption isotherms at 25, 45, and 65 degrees C of molybdenum solutions of
      concentration ranges between 10(-3) and 3x10(-2) M(Mo) (pH 4-5) on different
      alumina samples are investigated. The analysis is conducted using a modified
      Frumkin isotherm which takes a more realistic account of the lateral interaction
      between adsorbed species and considers that the adsorption takes place on the
      most basic OH groups on the surface of alumina. The results are discussed in view
      of the difference in solutions speciation, and the changes in the pH of the
      remaining supernatant solutions. The solution temperature, PZC of the used
      aluminas, the configuration of the basic OH groups on their surface, and the pore
      structure have been shown to intervene effectively. Copyright 2000 Academic
      Press.

PMID- 10882500
TI  - Polydispersity Effect on the Adsorption of Polymer Mixtures.
AB  - The changes in molecular mass distribution (MMD) after adsorption from solution
      in concentration regions below and above the critical concentration of
      overlapping have been studied for various polymers and their mixtures. It was
      found that the formation of entanglements in both binary and ternary solutions
      affects the changes in MMD. For binary and ternary solutions above the critical
      concentration of overlapping, C*, the entanglements lead to diminishing
      selectivity of adsorption of high-molecular-weight fractions. Simultaneously,
      transition through C* diminishes adsorption of the fractions of higher surface
      activity. It may be assumed that the entanglements play the role of an additional
      energetic barrier which macromolecules must overcome to be adsorbed. The
      transition through the critical concentration of overlapping for the case of
      binary solutions diminishes the selectivity of adsorption of high molecular
      fractions. Adsorption of polar polymers from the ternary solutions both below and
      above C* leads to the appearance of the bimodality of MMD due to adsorption of
      surface-active fractions. Copyright 2000 Academic Press.

PMID- 10882501
TI  - Adhesion of Colloidal SiO(2) Particles on ZnS-Type Phosphor Surfaces.
AB  - The interaction between colloidal SiO(2) particles and the surface of ZnS-type
      phosphors has been studied. The green emitting phosphor ZnS:Cu,Al,Au applied in
      color television tubes was chosen as a model compound. After the surface of the
      phosphor particles (d(50)=5.0 um) was treated in different manners like washing
      with H(2)O, HCl, or H(2)O(2) as well as precoating with colloidal ZnO particles
      (d(50)=81 nm), colloidal SiO(2) particles (d(50)=207 nm) were added. Thereafter,
      the amount of adhered SiO(2) was investigated based on SEM and ESCA analysis. By
      ESA measurements the surface charge of the colloids and the differently treated
      ZnS materials was investigated. Based on the experimental results it can be
      concluded that colloidal SiO(2) particles adhere sufficiently only if ZnO is
      present on the ZnS surface. The SiO(2) particles are located on top of the ZnO.
      Finally, the attractive interactions in the system ZnS-ZnO-SiO(2) are discussed
      in more detail. Copyright 2000 Academic Press.

PMID- 10882502
TI  - Adsorption of Polyelectrolyte-Nanoparticle Systems on Silica: Influence on
      Interaction Forces.
AB  - In this work, we have studied the interfacial properties of cationic
      polyelectrolyte (PE) and silica nanoparticle (NP) systems at macroscopic silica
      surfaces by means of ellipsometry. The influence of adsorbed layers on the
      interactions between silica surfaces was also investigated using the bimorph
      surface force apparatus. Added nanoparticles were observed to strongly swell the
      interfacial polyelectrolyte layers, an effect partly related to neutralization of
      charged polyelectrolyte groups. The effect was more pronounced for low charged
      than for highly charged polyelectrolytes. Overall, the presence of nanoparticles
      seemed to increase the repulsive interaction measured between silica surfaces.
      The force measured on approach was long range and quite strongly repulsive. On
      separation, an attractive bridging interaction was measured for polyelectrolyte
      covered surfaces. For the low charged polyelectrolyte used in the study, the
      force turned repulsive on addition of nanoparticles. For the highly charged
      polyelectrolyte used, a change from a very strong attraction (involving a jump of
      the surfaces out of contact) to a very long-range elastic attractive force was
      observed on adding nanoparticles. The long-range elastic force indicates that
      polymer chains and nanoparticles form a transient network in the gap between the
      surfaces. The observed difference in the outward force curves may explain why the
      addition of nanoparticles appears to improve, e.g., shear-resistance and
      reflocculation characteristics of polymeric flocculants. Copyright 2000 Academic
      Press.

PMID- 10882503
TI  - Effects of Pore-Pore Correlations on Capillary Condensation in an Ensemble of
      Slit-like Pores: Application of a Density Functional Theory.
AB  - Using a density functional method we study how the correlations between particles
      adsorbed in neighboring pores, forming a network of slit-like pores, influence
      the capillary condensation and the structure of adsorbed Lennard-Jones fluid. The
      calculations indicate that if the distance between two pores is small enough,
      these correlations lead to pronounced changes in the density profiles, to an
      increase of the critical temperature, and to the modifications in the coexistence
      envelope. Copyright 2000 Academic Press.

PMID- 10882504
TI  - Mathematical Modeling of Drug Release from Microemulsions: Theory in Comparison
      with Experiments.
AB  - The topic of this paper is the study of the drug release from a drug-loaded
      microemulsion by reverting to a new mathematical model overcoming some drawbacks
      of previously proposed models. In particular, attention is focused on the
      mathematical expression of the drug fluxes existing between the oil and water
      phases during drug release. Indeed, not only the drug release kinetics, but also
      the drug oil-water partition coefficient strongly depend on these fluxes. Two
      microemulsion are considered: the first is composed by water, Tween80 as
      surfactant, and Triacetin as oil phase, while the second is composed by water,
      Tween80 as surfactant, and a Triacetin-benzylic alcohol mixture (1 : 1) as oil
      phase. Both of them are loaded by Nimesulide, an oil-soluble drug of considerable
      industrial relevance. The drug release is performed by resorting to a permeation
      experiment (Franz cells apparatus) as it demonstrated to be the most reliable
      methodology. The good agreement between the experimental permeation data and the
      model best-fitting ensures that the most important phenomena ruling this kind of
      drug release were properly accounted for by the new proposed model. Copyright
      2000 Academic Press.

PMID- 10882505
TI  - Kinetic Analyses of Colloidal Crystallization in a Wide Range of Sphere
      Concentrations as Studied by Reflection Spectroscopy.
AB  - The nucleation and growth rates in the colloidal crystallization of silica
      spheres (103 nm in diameter) from 0.006 to 0.04 in volume fraction (straight phi)
      have been measured by reflection spectroscopy. Kinetics of the crystallization
      has been discussed in a wide sphere concentration range (from straight phi=0.0005
      to straight phi=0.04) using the data of this work and the previous work (110 nm
      in diameter) in exhaustively deionized aqueous suspensions. The induction period
      for nucleation decreases sharply as the sphere concentration increases. The
      nucleation rate increases substantially from 1x10(-3) to 1x10(7) mm(-3) s(-1)
      when straight phi increases from 0.0005 to 0.04. The crystal growth process
      consists of the fast growing step toward metastable crystals (rate v(1)) and slow
      growth accompanied with the reorientation toward stable ones (rate v(2)). The
      v(1) values increase first from 5 to 20 um/s and then turn back to 5 um/s after
      passing a maximum. v(1) above straight phi=0.01 remains at 5 um/s and is
      insensitive to sphere concentration. The slow step is observed in the high-sphere
      concentrations only, and v(2) decreases sharply from 3 um/s to 0.7 nm/s when
      sphere concentration increases from 0.004 to 0.04 in volume fraction. Importance
      of the electrostatic intersphere repulsion by overlapping of the electrical
      double layers and the cooperative and synchronized fluctuation of colloidal
      spheres in the crystallization processes are supported strongly. Copyright 2000
      Academic Press.

PMID- 10882506
TI  - Mechanism and Kinetics of Hexamethyldisilazane Reaction with a Fumed Silica
      Surface.
AB  - Quantum chemical calculations of the reaction of hexamethyldisilazane with silica
      indicates a two-step mechanism. The first, rate-determining step results in
      trimethylsilylation of a surface silanol and formation of trimethylaminosilane.
      The second step involves reaction of a trimethylaminosilane reactive intermediate
      to form a trimethylsilyl surface species and ammonia. This two-step mechanism was
      applied to analyze data of the kinetics of hexamethyldisilazane reaction with
      fumed silica using custom interactive software. Both the extent of surface
      reaction and the loss of hexamethyldisilazane from toluene solution were
      monitored by FT-IR spectroscopy as a function of time. Data analysis indicates
      that under the conditions studied the reaction is adsorption rate limited. The
      entire reaction can be explained in terms of reaction with non-hydrogen-bonded
      surface silanols, though hydrogen-bonded silanols act as adsorption sites.
      Copyright 2000 Academic Press.

PMID- 10882507
TI  - Latex Surface and Bulk Coagulation Induced by Solvent Vapors.
AB  - Latex exposure to solvent vapors leads to highly specific changes in latex
      stability as well as on the morphologies of the particle association products,
      depending on the latex and solvent used. Examples of solvent vapor-induced
      aggregation are given: surface films are obtained on two PS latexes; in one case,
      the film surface is mirror-reflective and very flat, as evidenced by AFM. Another
      PS latex coagulates under exposure to acetone vapors, and the morphologies of the
      coagula are highly sensitive to the exposure conditions. This latex yields a
      highly porous foam-like structure, in which particles are strongly coalesced but
      form percolating patches around the pores. The same latex but under other
      conditions produces a coagulum of large numbers of aggregated particles with a
      raspberry-like morphology. Density centrifugation experiments show that the
      effect of solvents on different latex fractions is not uniform, and some
      fractions show larger density changes than others, thus evidencing a variability
      in their swelling ability. Copyright 2000 Academic Press.

PMID- 10882508
TI  - Estimation of Distribution Parameters of Organic Solutes in Cloud Point
      Extraction.
AB  - Cloud point extraction of aromatic solutes in the system containing nonionic
      surfactant polyoxyethylene nonylphenyl ether (PONPE 10) was discussed in terms of
      their hydrogen-bond donating and accepting abilities and hydrophobicity. It was
      shown that the Abraham model could be used to estimate the distribution ratio and
      the effect of aromatic solutes on the cloud point. Copyright 2000 Academic Press.

PMID- 10882509
TI  - The Influence of a Long-Chain Hydrocarbon on the Retention of Probes Differing in
      the Type of Intermolecular Interactions.
AB  - The surface properties of entirely hydroxylated, as well as significantly
      dehydroxylated, silica gel were investigated by means of the gas phase titration
      method. n-Tridecane was applied as blocking agent, while n-octane, benzene, and
      chloroform were the testing probes. The results obtained were compared to those
      from the previous investigation, where ethylmethylketone was used as blocking
      agent. After the proper recalculation of n-tridecane surface concentration it was
      stated that the titration curves for n-octane coincided for both blocking agents.
      The changes in nonspecific adsorption interaction do not depend on the type of
      the blocking agent intermolecular interactions. Copyright 2000 Academic Press.

PMID- 10882510
TI  - Reactivity and Coaggregation of p-Nitrophenyl Esters with Polymer Micelles at
      Solid Surfaces.
AB  - The polymer micelle, poly[(N-(n-dodecyl)-4-vinylpyridiniumco-N-ethyl-4
      vinylpyridinium) bromide], PDE, containing 30% dodecyl groups has been found to
      promote the adhesion of lipophiles to various surfaces including quartz,
      polystyrene, and poly(methyl methacrylate) cuvette surfaces from aqueous
      solutions. The adsorption of PDE/ester coaggregates to the surfaces was studied
      by hydrolysis of p-nitrophenyl esters in aqueous PDE(30) solutions. The extent of
      reaction of p-nitrophenyl myristate, an ester with a linear acyl carbon chain
      length of 14, can be viewed as a probe to study the adhesion of the PDE/ester
      coaggregates to the cuvette surfaces. The difference between initial
      concentration of ester and concentration of hydrolysis product, p-nitrophenoxide
      ion, gives the concentration of unreacted ester in the aggregates or film
      adhering to the solid surface. Up to 40% of p-nitrophenyl myristate was found
      unreacted on the surface of quartz cuvettes after apparent completion of the
      reaction. No adhesion of the related caproate ester with a linear acyl carbon
      chain length of 6 was detected. Copyright 2000 Academic Press.

PMID- 10882511
TI  - On the General Expression for the Electrophoretic Mobility of a Soft Particle.
AB  - Electrokinetic equations for electrophoresis of a soft particle (that is, a hard
      particle covered with a layer of polyelectrolytes) have been solved previously
      under the conditions that the net force acting on the soft particle as a whole
      (the particle core plus the polyelectrolyte layer) must be zero and that the
      electrical force acting on the polymer segment is balanced with a frictional
      force exerted by the liquid flow (J. Colloid Interface Sci. 163, 474 (1994)). In
      the present work we replaced the latter condition by the alternative and more
      appropriate condition that pressure is continuous at the boundary between the
      surface layer and the surrounding electrolyte solution to solve the
      electrokinetic equations and obtained the general mobility expression for the
      electrophoretic mobility of a spherical soft particle. It is found that the
      general mobility expression thus obtained reproduces all of the approximate
      mobility expressions derived previously and, in addition, that the continuous
      pressure condition leads to the correct limiting behavior of the electrophoretic
      mobility in the case where the frictional coefficient tends to zero (this
      behavior cannot be derived from the force balance condition for the
      polyelectrolyte layer). Copyright 2000 Academic Press.

PMID- 10882512
TI  - Embryo implantation.

PMID- 10882513
TI  - Down-regulation of the inositol 1,4,5-trisphosphate receptor in mouse eggs
      following fertilization or parthenogenetic activation.
AB  - Fertilization in mammalian eggs is characterized by the presence of intracellular
      calcium ([Ca(2+)]i) oscillations. In mouse eggs, these oscillations cease after a
      variable period of time and this is accompanied by a decrease in inositol 1,4,5
      trisphosphate receptor (IP3R) responsiveness and down-regulation of the IP3R type
      1 (IP3R-1). To investigate the signaling pathway responsible for inducing IP3R-1
      down-regulation during fertilization, mouse eggs were exposed to or injected with
      several Ca(2+)-releasing agonists and the amounts of IP3R-1 immunoreactivity
      evaluated by Western blotting. Exposure to ethanol or ionomycin, which induce a
      single [Ca(2+)]i rise, failed to signal down-regulation of IP3R-1. However,
      [Ca(2+)]i oscillations induced by injection of boar sperm fractions (SF), which
      presumably stimulate production of IP3, or adenophostin A, an IP3R agonist, both
      induced down-regulation of IP3R-1 of a magnitude similar to or greater than that
      observed after fertilization. Exposure to thimerosal, an oxidizing agent that
      modifies the IP3R without stimulating production of IP3, also initiated down
      regulation of IP3R-1, although oscillations initiated by SrCl(2) failed to evoke
      down-regulation of IP3R-1. The degradation of IP3R-1 in mouse eggs appears to be
      mediated by the proteasome pathway because it was inhibited by preincubation with
      lactacystin, a very specific proteasome inhibitor. We therefore suggest that
      persistent stimulation of the phosphoinositide pathway in mouse eggs by the sperm
      during fertilization or by injection of SF leads to down-regulation of the IP3R
      1.

PMID- 10882514
TI  - Inositol 1,4,5-trisphosphate receptors are downregulated in mouse oocytes in
      response to sperm or adenophostin A but not to increases in intracellular Ca(2+)
      or egg activation.
AB  - Fertilization in mammals stimulates a series of Ca(2+) oscillations that continue
      for 3-4 h. Cell-cycle-dependent changes in the ability to release Ca(2+) are one
      mechanism that leads to the inhibition of Ca(2+) transients after fertilization.
      The downregulation of InsP(3)Rs at fertilization may be an additional mechanism
      for inhibiting Ca(2+) transients. In the present study we examine the mechanism
      of this InsP(3)R downregulation. We find that neither egg activation nor Ca(2+)
      transients are necessary or sufficient for the stimulation of InsP(3)R
      downregulation. First, parthenogenetic activation fails to stimulate
      downregulation. Second, downregulation persists when fertilization-induced Ca(2+)
      transients and egg activation are inhibited using BAPTA. Third, downregulation
      can be induced in immature oocytes that do not undergo egg activation. Other than
      fertilization, the only stimulus that downregulated InsP(3)Rs was microinjection
      of the potent InsP(3)R agonist adenophostin A. InsP(3)R downregulation was
      inhibited by the cysteine protease inhibitor ALLN but MG132 and lactacystin were
      not effective. Finally, we have injected maturing oocytes with adenophostin A and
      produced MII eggs depleted of InsP(3)Rs. We show that sperm-induced Ca(2+)
      signaling is inhibited in such InsP(3)R-depleted eggs. These data show that
      InsP(3)R binding is sufficient for downregulation and that Ca(2+) signaling at
      fertilization is mediated via the InsP(3)R.

PMID- 10882515
TI  - Chamber formation and morphogenesis in the developing mammalian heart.
AB  - In this study we challenge the generally accepted view that cardiac chambers form
      from an array of segmental primordia arranged along the anteroposterior axis of
      the linear and looping heart tube. We traced the spatial pattern of expression of
      genes encoding atrial natriuretic factor, sarcoplasmic reticulum calcium ATPase,
      Chisel, Irx5, Irx4, myosin light chain 2v, and beta-myosin heavy chain and
      related these to morphogenesis. Based on the patterns we propose a two-step model
      for chamber formation in the embryonic heart. First, a linear heart forms, which
      is composed of "primary" myocardium that nonetheless shows polarity in phenotype
      and gene expression along its anteroposterior and dorsoventral axes. Second,
      specialized ventricular chamber myocardium is specified at the ventral surface of
      the linear heart tube, while distinct left and right atrial myocardium forms more
      caudally on laterodorsal surfaces. The process of looping aligns these primordial
      chambers such that they face the outer curvature. Myocardium of the inner
      curvature, as well as that of inflow tract, atrioventricular canal, and outflow
      tract, retains the molecular signature originally found in linear heart tube
      myocardium. Evidence for distinct transcriptional programs which govern
      compartmentalization in the forming heart is seen in the patterns of expression
      of Hand1 for the dorsoventral axis, Irx4 and Tbx5 for the anteroposterior axis,
      and Irx5 for the distinction between primary and chamber myocardium.

PMID- 10882516
TI  - Presence of functional sarcoplasmic reticulum in the developing heart and its
      confinement to chamber myocardium.
AB  - During development fast-contracting atrial and ventricular chambers develop from
      a peristaltic-contracting heart tube. This study addresses the question of
      whether chamber formation is paralleled by a matching expression of the
      sarcoplasmic reticulum (SR) Ca(2+) pump. We studied indo-1 Ca(2+) transients
      elicited by field stimulation of linear heart tube stages and of explants from
      atria and outflow tracts of the prototypical preseptational E13 rat heart. Ca(2+)
      transients of H/H 11+ chicken hearts, which constitute the prototypic linear
      heart tube stage, were sensitive to verapamil only, indicating a minor
      contribution of Ca(2+)-triggered SR Ca(2+) release. Outflow tract transients
      displayed sensitivity to the inhibitors similar to that of the linear heart tube
      stages. Atrial Ca(2+) transients disappeared upon addition of ryanodine,
      tetracaine, or verapamil, indicating the presence of Ca(2+)-triggered SR Ca(2+)
      release. Quantitative radioactive in situ hybridization on sections of E13 rat
      hearts showed approximately 10-fold higher SERCA2a mRNA levels in the atria
      compared to nonmyocardial tissue and approximately 5-fold higher expression in
      compact ventricular myocardium. The myocardium of atrioventricular canal, outflow
      tract, inner curvature, and ventricular trabecules displayed weak expression.
      Immunohistochemistry on sections of rat and human embryos showed a similar
      pattern. The significance of these findings is threefold. (i) A functional SR is
      present long before birth. (ii) SR development is concomitant with cardiac
      chamber development, explaining regional differences in cardiac function. (iii)
      The pattern of SERCA2a expression underscores a manner of chamber development by
      differentiation at the outer curvature, rather than by segmentation of the linear
      heart tube.

PMID- 10882517
TI  - Regulation of gut and heart left-right asymmetry by context-dependent
      interactions between xenopus lefty and BMP4 signaling.
AB  - The Lefty subfamily of TGFbeta signaling molecules has been implicated in early
      development in mouse, zebrafish, and chick. Here, we show that Xenopus lefty
      (Xlefty) is expressed both bilaterally in symmetric midline domains and
      unilaterally in left lateral plate mesoderm and anterior dorsal endoderm. To
      examine the roles of Xlefty in left-right development, we created a system for
      scoring gut asymmetry and examined the effects of unilateral Xlefty misexpression
      on gut development, heart development, and Xnr-1 and XPitx2 expression. In
      contrast to the unilateral effects of Vg1, Activin, Nodal, or BMPs, targeted
      expression of Xlefty in either the left or the right side of Xenopus embryos
      randomized the direction of heart looping, gut coiling, and left-right
      positioning of the gut and downregulated the asymmetric expression of Xnr-1 and
      XPitx2. It is currently thought that Lefty proteins act as feedback inhibitors of
      Nodal signaling. However, this would not explain the effects of right-sided
      Xlefty misexpression. Here, we show that Xlefty interacts with the signaling
      pathways of other members of the TGFbeta family during left-right development.
      Results from coexpression of Xlefty and Vg1 indicate that Xlefty can nullify the
      effects of Vg1 ectopic expression and that Xlefty is downstream of left-sided Vg1
      signaling. Results from coexpression of Xlefty and XBMP4 indicate that XLefty and
      XBMP4 interact both synergistically and antagonistically in a context-dependent
      manner. We propose a model in which interactions of Xlefty with multiple members
      of the TGFbeta family enhance the differences between the right-sided
      BMP/ALK2/Smad pathway and the left-sided Vg1/anti-BMP/Nodal pathway, leading to
      left-right morphogenesis of the gut and heart.

PMID- 10882518
TI  - Importin-alpha3 is required at multiple stages of Drosophila development and has
      a role in the completion of oogenesis.
AB  - The Drosophila importin-alpha3 gene was isolated through its interaction with the
      large subunit of the DNA polymerase alpha in a two-hybrid screen. The predicted
      protein sequence of Importin-alpha3 is 65-66% identical to those of the human and
      mouse importin-alpha3 and alpha4 and 42.7% identical to that of Importin-alpha2
      (Oho31/Pendulin), the previously reported Drosophila homologue. Both Importin
      alpha3 and Importin-alpha2 interact with similar subsets of proteins in vitro,
      one of which is Ketel, the importin-beta homologue of Drosophila. importin-alpha3
      is an essential gene, whose encoded protein is expressed throughout development.
      During early embryogenesis, Importin-alpha3 accumulates at the nuclear membrane
      of cleavage nuclei, whereas after blastoderm formation it is characteristically
      found within the interphase nuclei. Nuclear localisation is seen in several
      tissues throughout subsequent development. During oogenesis its concentration
      within the nurse cell nuclei increases during stages 7-10, concomitant with a
      decline in levels in the oocyte nucleus. Mutation of importin-alpha3 results in
      lethality throughout pupal development. Surviving females are sterile and show
      arrest of oogenesis at stages 7-10. Thus, Importin-alpha3-mediated nuclear
      transport is essential for completion of oogenesis and becomes limiting during
      pupal development. Since they have different expression patterns and subcellular
      localisation profiles, we suggest that the two importin-alpha homologues are not
      redundant in the context of normal Drosophila development.

PMID- 10882519
TI  - Retinoid signaling is required to complete the vertebrate cardiac left/right
      asymmetry pathway.
AB  - Vitamin A-deficient (VAD) quail embryos have severe abnormalities, including a
      high incidence of reversed cardiac situs. Using this model we examined in vivo
      the physiological function of vitamin A in the left/right (L/R) cardiac asymmetry
      pathway. Molecular analysis reveals the expression of early asymmetry genes
      activin receptor IIa, sonic hedgehog, Caronte, Lefty-1, and Fgf8 to be unaffected
      by the lack of retinoids, while expression of the downstream genes nodal-related,
      snail-related (cSnR), and Pitx2 is altered. In VAD embryos nodal expression in
      left lateral plate mesoderm (LPM) is severely downregulated and the expression
      domain altered during neurulation. Similarly, the expression of cSnR in the right
      LPM and of Pitx2 in the left side posterior heart-forming region (HFR) is
      downregulated in the VAD embryos. The lack of retinoids does not cause
      randomization or ectopic expression of nodal, cSnR, or Pitx2. At the six- to
      eight-somite stage nodal is expressed transiently in the left posterior HFR of
      normal quail embryos; this expression is missing in VAD embryos and may be linked
      to the loss of Pitx2 expression in this region of VAD quail embryos.
      Administration of retinoids to VAD embryos prior to the six-somite stage rescues
      the expression of nodal, cSnR, and Pitx2 as well as the randomized VAD cardiac
      phenotype. There is an absolute requirement for retinoids at the four- to five
      somite developmental window for cardiogenesis and cardiac L/R specification to
      proceed normally. We conclude that retinoids do not regulate the left/right
      specific sidedness assignments for expression of genes on the vertebrate cardiac
      asymmetry pathway, but are required during neurulation for the maintenance of
      adequate levels of their expression and for the development of the posterior
      heart tube and a loopable heart. Cardiac asymmetry may be but one of several
      critical events regulated by retinoid signaling in the retinoid-sensitive
      developmental window.

PMID- 10882520
TI  - Expression of Otx homeodomain proteins induces cell aggregation in developing
      zebrafish embryos.
AB  - In the zebrafish embryo, cells fated to give rise to the rostral brain move in a
      concerted fashion and retain tissue coherence during morphogenesis. We
      demonstrate here that Otx proteins have a dramatic effect on cell-cell
      interactions when expressed ectopically in the zebrafish embryo. Injection of
      zebrafish Otx1 or Drosophila otd RNAs into a single cell at the 16-cell stage
      results in aggregation of descendants of the injected cell. The Otx/Otd
      homeodomain is necessary for aggregation and appears to be sufficient for the
      effect when substituted for the homeodomain of an unrelated homeodomain protein.
      When cells containing injected zOtx1 RNA are limited to the area that is normally
      fated to become the anterior brain and neural retina, the induced aggregates
      contribute to anterior brain and retina tissues. In many other embryonic regions,
      which do not express endogenous zOtx1, the aggregates appear to be incompatible
      with normal development and do not integrate into developing tissues. By using an
      activatable Otx1-glutocorticoid receptor fusion protein that results in the
      stimulation of cell association, we demonstrate that cell aggregates can form as
      a result of Otx1 activity even after gastrulation is completed. Time-lapse
      analysis of cell movements show that cell aggregation occurs with only a slight
      inhibition of the rate of convergence. These results suggest that promotion of
      cell adhesion or mediation of cell repulsion may be one of the normal functions
      of the Otx proteins in the establishment of the anterior brain.

PMID- 10882521
TI  - Functional and molecular reorganization of the nucleolar apparatus in maturing
      mouse oocytes.
AB  - In mammalian preovulatory oocytes, rRNA synthesis is down-regulated until egg
      fertilization and zygotic genome reactivation, but the underlying regulatory
      mechanisms of this phenomenon are poorly characterized. We examined the molecular
      organization of the rRNA synthesis and processing machineries in fully grown
      mouse oocytes in relation to ongoing rDNA transcription and oocyte progression
      throughout meiosis. We show that, at the germinal vesicle stage, the two RNA
      polymerase I (RNA pol I) subunits, RPA116 and PAF53/RPA53, and the nucleolar
      upstream binding factor (UBF) remain present irrespective of ongoing rDNA
      transcription and colocalize in stoichiometric amounts within discrete foci at
      the periphery of the nucleolus-like bodies. These foci are spatially associated
      with the early pre-rRNA processing protein fibrillarin and in part with the pre
      ribosome assembly factor B23/nucleophosmin. After germinal vesicle breakdown, the
      RNA pol I complex disassembles in a step-wise manner from chromosomes, while UBF
      remains associated with chromosomes until late prometaphase I. Dislodging of UBF,
      but not of RNA pol I, is impaired by the phosphatase inhibitor okadaic acid, thus
      strengthening the idea of a relationship between UBF dynamics and protein
      phosphorylation. Since neither RNA pol I, UBF, fibrillarin, nor B23 is detected
      at metaphase II, i.e., the normal stage of fertilization, we conclude that these
      nucleolar proteins are not transported to fertilized eggs by maternal
      chromosomes. Together, these data demonstrate an essential difference in the
      dynamics of the major nucleolar proteins during mitosis and meiosis.

PMID- 10882522
TI  - Isolation and characterization of the novel popeye gene family expressed in
      skeletal muscle and heart.
AB  - We identified a novel gene family in vertebrates which is preferentially
      expressed in developing and adult striated muscle. Three genes of the Popeye
      (POP) family were detected in human and mouse and two in chicken. Chromosomal
      mapping indicates that Pop1 and Pop3 genes are clustered on mouse chromosome 10,
      whereas Pop2 maps to mouse chromosome 16. We found evidence that POP1 and POP3 in
      chicken may also be linked and multiple transcript isoforms are generated from
      this locus. The POP genes encode proteins with three potential transmembrane
      domains that are conserved in all family members. Individual POP genes exhibit
      specific expression patterns during development and postnatally. Chicken POP3 and
      mouse Pop1 are first preferentially expressed in atrium and later also in the
      subepicardial compact layer of the ventricles. Chicken POP1 and mouse Pop2 are
      expressed in the entire heart except the outflow tract. All three Pop genes are
      expressed in heart and skeletal muscle of the adult mouse and lower in lung. Pop1
      and Pop2 expression is upregulated in uterus of pregnant mice. Like the mouse
      genes, human POP genes are predominantly expressed in skeletal and cardiac
      muscle. The strong conservation of POP genes during evolution and their
      preferential expression in heart and skeletal muscle suggest that these novel
      proteins may have an important function in these tissues in vertebrates.

PMID- 10882523
TI  - Lens-specific VEGF-A expression induces angioblast migration and proliferation
      and stimulates angiogenic remodeling.
AB  - Vascular endothelial growth factor (VEGF) is a secreted mitogen which
      specifically stimulates proliferation of vascular endothelial cells in vitro and
      in vivo. Its expression pattern is consistent with it being an important
      regulator of vasculogenesis and angiogenesis, and targeted disruption of VEGF-A
      has demonstrated that it is essential for vascular development. To determine if
      VEGF-A was sufficient to alter vascularization in the eye we generated transgenic
      mice which express human VEGF-A(165) specifically in the lens. Expression of
      transgenic VEGF-A led to excessive proliferation and accumulation of disorganized
      angioblasts and endothelial cells around the lens. The results support the
      hypothesis that VEGF-A can initiate the process of vascularization by stimulating
      chemoattraction and proliferation of angioblasts and endothelial cells and that
      VEGF-A expression can stimulate angiogenic remodeling. However, VEGF-A alone was
      not sufficient to direct blood vessel organization or maturation.

PMID- 10882524
TI  - Pax1/Pax9-Related genes in an agnathan vertebrate, Lampetra japonica: expression
      pattern of LjPax9 implies sequential evolutionary events toward the gnathostome
      body plan.
AB  - Among the transcription factor gene families, Pax genes play important and unique
      roles in morphological patterning of animal body plans. Of these, Group I Pax
      genes (Pax1 and Pax9) are expressed in the endodermal pharyngeal pouches in many
      groups of deuterostomes, and vertebrates seem to have acquired more extensive
      expression domains in embryos. To understand the evolution of Pax1/Pax9-related
      genes in basal groups of vertebrates, their cognates were isolated from the
      Japanese marine lamprey, Lampetra japonica. RT-PCR of larval lamprey cDNA yielded
      two different fragments containing vertebrate Pax1- and Pax9-like paired domains.
      The Pax9 orthologue was isolated and named LjPax9. Whole-mount in situ
      hybridization revealed that this gene was expressed in endodermal pharyngeal
      pouches, mesenchyme of the velum (the oral pumping apparatus) and the hyoid arch,
      and the nasohypophysial plate, but not in the somitic mesoderm of the lamprey
      embryo. These expression patterns could be regarded as a link between the basal
      chordates and the gnathostomes and are consistent with the phylogenetic position
      of the lamprey. Especially, the appearance of neural crest seemed to be the basis
      of velar expression. Homology of the velum and the jaw is also discussed based on
      the LjPax9 expression in the first pharyngeal pouch and in the velar mesenchyme.
      We conclude that Pax9 genes have sequentially expanded into new expression
      domains through evolution as more complicated body plans emerged.

PMID- 10882525
TI  - The expression and stage-specific localization of protein kinase C isotypes
      during mouse preimplantation development.
AB  - Signaling events mediate many processes that act during embryogenesis to initiate
      the program of early development. Within the cell many of these changes are
      mediated through the activation or inactivation of kinases and phosphatases.
      Protein kinase C (PKC) is one kinase that has been shown to be involved in at
      least two developmental transitions during early development, fertilization and
      embryonic compaction. PKC is a family of kinases whose various isotypes have
      differing requirements for activation of the kinase that include the availability
      of calcium, diacylglycerol, and negatively charged phospholipids. The presence of
      more than one isotype in an egg or blastomere of the embryo would provide the
      possibility that different isotypes mediate distinct signaling pathways in the
      cells. To address this possibility the different isotypes of PKC were examined at
      the mRNA and protein levels during preimplantation development in the mouse. Our
      results demonstrate that seven isotypes of PKC are present during preimplantation
      development in mouse, some are of maternal origin and others appear after
      fertilization. Two isotypes have a stage-dependent nuclear localization. In
      addition, within each blastomere PKC isotypes occupy different subcellular
      locations in a stage-dependent fashion.

PMID- 10882526
TI  - The homeobox gene Hesx1 is required in the anterior neural ectoderm for normal
      forebrain formation.
AB  - The homeobox gene Hesx1 is expressed in the anterior visceral endoderm (AVE),
      anterior axial mesendoderm (AME), and anterior neural ectoderm (ANE) during early
      mouse embryogenesis. Previous studies have shown that Hesx1 is essential for
      normal murine forebrain development. Hesx1 homozygous mutants showed variable
      forebrain truncations ranging from mild to severe lack of forebrain tissue. Here,
      we have investigated the requirement of Hesx1 in the AVE, AME, and ANE using
      chimeric and in situ hybridization analyses to understand better the nature of
      the forebrain defects. Chimeric embryos composed predominantly of Hesx1(+/+)
      cells developing within Hesx1(-/-) visceral endoderm showed no evident forebrain
      abnormalities. In contrast, injection of Hesx1(-/-) ES cells into wild-type
      blastocysts gave rise to chimeras with forebrain defects similar to those
      observed in the Hesx1(-/-) mutants. RNA in situ hybridization analysis showed
      that the AVE and AME markers Cerrl, Lim1, and Shh were normally expressed in 6.5-
      and 7.5-dpc Hesx1(-/-) mutants. Expression of the ANE markers Six3 and Rax/Rx was
      also unperturbed in the Hesx1(-/-) mutants from late gastrula to late headfold
      stages. However, transcripts for both genes were markedly reduced by the early
      somite stage, about 24 h after Hesx1 is first expressed in the ANE. Therefore,
      Hesx1 seems to be required autonomously in the ANE for normal forebrain
      formation.

PMID- 10882527
TI  - The MADS-Box factor CeMEF2 is not essential for Caenorhabditis elegans myogenesis
      and development.
AB  - MEF2 is an evolutionarily conserved MADS (MCM1, Agamous, Deficiens, and serum
      response factor) box-type transcription factor that plays a critical role in
      vertebrate and Drosophila melanogaster myogenesis. We have addressed the
      developmental role of the single MEF2-like factor, CeMEF2, in Caenorhabditis
      elegans. Using expression assays and two mef-2 deletion alleles, we show that
      CeMEF2 is not required for proper myogenesis or development. Moreover, a putative
      null mef-2 allele fails to enhance or suppress the phenotypes of mutants in
      CeMyoD or CeTwist. Our results suggest that despite its evolutionary conservation
      of sequence and DNA binding properties, CeMEF2 has adopted a divergent role in
      development in the nematode compared with Drosophila and vertebrates.

PMID- 10882528
TI  - A mode of regulation of beta-catenin signaling activity in Xenopus embryos
      independent of its levels.
AB  - The signaling activity of beta-catenin is thought to be regulated by
      phosphorylation of a cluster of N-terminal serines, putative sites for GSK3beta.
      In the prevailing model in the literature, GSK3beta-dependent phosphorylation of
      these sites targets beta-catenin for ubiquitin-mediated degradation. Wnt
      signaling inhibits GSK3beta activity and this blocks degradation, allowing beta
      catenin to accumulate and signal. We show here that beta-catenin activity is not
      regulated solely by protein stability. Mutations in the putative GSK3beta
      phosphorylation sites of beta-catenin enhance its signaling activity, but this
      cannot be accounted for by accumulation of either total or cadherin-free protein.
      Instead, the mutant protein has a threefold higher specific activity than the
      wild type both in vivo and in an in vitro signaling assay. We conclude that the N
      terminal serines convey a layer of regulation upon beta-catenin signaling in
      addition to the effects these sites exert upon protein stability.

PMID- 10882529
TI  - Calcium influx mediates the voltage-dependence of sperm entry into sea urchin
      eggs.
AB  - Sperm entry was monitored in voltage-clamped sea urchin eggs following
      insemination in a variety of artificial seawaters. In regular seawater,
      maintaining the membrane potential at increasingly negative values progressively
      inhibits sperm entry. Reducing [Ca(2+)](o) relieves the inhibition, shifting the
      sperm entry vs voltage relationship toward more negative potentials. Raising
      [Ca(2+)](o) shifts the relationship in the other direction. Large changes in
      [Na(+)](o) or [Mg(2+)](o) do not affect sperm entry although changing [Na(+)](o)
      dramatically changes the currents following sperm attachment. Applying one of
      seven different calcium channel blockers or replacing Ca(2+) with Ba(2+) or
      Sr(2+) or microinjecting calcium chelators into the cytoplasm relieves the block
      to sperm entry at negative potentials. We conclude that the block to sperm entry
      at negative potentials is mediated by calcium which crosses the membrane and acts
      at an intracellular site.

PMID- 10882531
TI  - Induction of lytic enzymes by the interaction of Ustilago maydis with Zea mays
      tissues.
AB  - The nonpathogenic (FB-2) and pathogenic (FB-D12) strains of Ustilago maydis were
      grown in medium supplemented with different carbon sources including
      monosaccharides, polysaccharides, and plant tissues. Both strains were able to
      grow on all substrates, with doubling times varying from 2 to 25 h depending on
      the carbon source. Plant tissues supplied as carbon source induced lytic enzymes
      differentially; pectate lyase and cellulase activities were induced
      preferentially by apical stem meristem in strain FB-D12, whereas leaves
      preferentially induced xylanase and cellulase activities in strain FB2. Stems
      induced polygalacturonase activity in both strains. All enzyme activities, except
      cellulase in the FB-D12 strain, were detected at a low level when U. maydis was
      grown on glucose. In planta, chlorosis and production of teliospores were
      paralleled by an increase in pectate lyase activity. Anthocyanin production and
      formation of galls and teliospores correlated with polygalacturonase expression
      whereas cellulase activity increased only during the stage of anthocyanin
      production and gall formation. Expression of xylanase activity coincided with the
      last stage of teliospore formation.

PMID- 10882532
TI  - Diploid strains of the pathogenic basidiomycete Cryptococcus neoformans are
      thermally dimorphic.
AB  - Cryptococcus neoformans is an opportunistic human pathogenic fungus with a
      defined sexual cycle. Clinical and environmental isolates of C. neoformans are
      haploid, and the diploid stage of the lifecycle is thought to be transient and
      unstable. In contrast, we find that diploid strains are readily obtained
      following genetic crosses of congenic MATalpha and MATa strains. At 37 degrees C,
      the diploid strains grow as yeast cells with a single nucleus that is larger than
      a haploid nucleus, contains a 2n content of DNA by FACS analysis, and is
      heterozygous for the MATalpha and MATa loci. At 24 degrees C, these diploid self
      fertile strains filament and sporulate, producing recombinant haploid progeny in
      which meiotic segregation has occurred. In contrast to dikaryotic filament cells
      that are typically linked by fused clamp connections during mating, self-fertile
      diploid strains produce monokaryotic filament cells with unfused clamp
      connections. We also show that these diploid strains can be transformed and
      sporulated and that an integrated selectable marker segregates in a mendelian
      fashion. The diploid state could play novel roles in the lifecycle and virulence
      of the organism and can be exploited for the analysis of essential genes.
      Finally, the observation that dimorphism is thermally regulated suggests
      similarities between the lifecycle of C. neoformans and other thermally dimorphic
      human pathogenic fungi, including Histoplasma capsulatum, Blastomyces
      dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis, and Sporothrix
      schenkii.

PMID- 10882534
TI  - The reliability of the Aspergillus nidulans physical map.
AB  - Here we report an evaluation of the Aspergillus nidulans physical map (a cosmid
      contig map) emphasizing quantification and description of obvious mapping errors.
      Classification and appraisal of mapping errors should be helpful to researchers
      working on particular regions of the map. We estimate between 47 (4.1%) and 63
      (5.4%) probe/clone-linking errors. The majority of identified false links (38)
      permit reciprocal exchanges among linking clones located on disconnected mapping
      regions. The order of adjacent clones or probes on the affected contigs remains
      unchanged. In addition we describe an Internet-accessible resource in which
      genetic and physical maps were integrated through a graphic interface. A simple
      search engine allows retrieval of cosmids from redundant clone lists and provides
      links to the minimal clone order. Integration of genetic and physical maps
      provides an additional level of accountability in which mapping discrepancies are
      visually located.

PMID- 10882533
TI  - Senescent: a new Neurospora crassa nuclear gene mutant derived from nature
      exhibits mitochondrial abnormalities and a "death" phenotype.
AB  - Fungi are capable of potentially unlimited growth. We resolved nuclear types from
      multinuclear mycelium of a phenotypically normal wild isolate of the fungus
      Neurospora intermedia by plating its uninucleate microconidia and obtained a
      strain which, unlike the "parent" strain, exhibited clonal senescence in
      subcultures. The mutant gene, senescent, was introgressed into N. crassa and
      mapped four map units to the right of the his-1 locus on linkage group VR.
      senescent is the first nuclear gene mutant of Neurospora derived from nature that
      shows the death phenotype. Death of the sen mutant occurred faster at 34 degrees
      C than at 22 or 26 degrees C. Measurements of oxygen uptake of conidia using
      respiratory inhibitors and the spectrophotometric analyses of mitochondrial
      cytochromes showed that in sen cultures grown at 34 degrees C, cytochromes b and
      aa(3) were present but cytochrome c was absent. By contrast at 26 degrees C,
      cytochromes b and c were present but cytochrome aa(3) was diminished in the late
      subcultures. This suggested that the sen mutation does not affect the potential
      to produce functional cytochromes. The deficiency of the respiratory chain
      cytochromes may not be the cause of death of the sen mutant because the
      cytochrome c and aa(3) mutants of N. crassa are capable of sustained growth
      whereas sen is not. Possible explanations for the observations are discussed.

PMID- 10882535
TI  - A tip-high gradient of a putative plasma membrane SNARE approximates the
      exocytotic gradient in hyphal apices of the fungus Neurospora crassa.
AB  - Antibodies to the Saccharomyces cereviseae plasma membrane t-SNARE Sso2p identify
      a putative 39-kDa homologue in Neurospora crassa. The 39-kDa protein is enriched
      in plasma membrane (PM) and occurred with other membranes. It is extractable by
      detergent, but not chaotropic or alkali agents, suggesting membrane insertion.
      Immunoprecipitation with anti-Sso2p coprecipitated a approximately 100-kDa, Mg(+)
      ATP-sensitive band with the 39-kDa protein, suggesting a ternary SNARE complex.
      Affinity-purified anti-Sso2p gave hyphal staining patterns most consistent with
      protein localization on both the PM and intracellular exocytotic apical wall
      vesicles. The PM staining in hyphal apices formed a tip-high gradient, not as
      steep as that predicted by the "hyphoid equation," but closer to published
      gradients of cell wall matrix deposition. We conclude that the t-SNAREs are
      transported to the PM on the apical vesicles, but their tip-high gradient alone
      is insufficient to explain the vesicle fusion gradient in growing tips.

PMID- 10882536
TI  - Analysis of two Aspergillus nidulans genes encoding extracellular proteases.
AB  - Characterization of prtADelta mutants, generated by gene disruption, showed that
      the prtA gene is responsible for the majority of extracellular protease activity
      secreted by Aspergillus nidulans at both neutral and acid pH. The prtA delta
      mutation was used to map the prtA gene to chromosome V. Though aspartic protease
      activity has never been reported in A. nidulans and the prtADelta mutants appear
      to lack detectable acid protease activity, a gene (prtB) encoding a putative
      aspartic protease was isolated from this species. Comparison of the deduced amino
      acid sequence of PrtB to the sequence of other aspergillopepsins suggests that
      the putative prtB gene product contains an eight-amino-acid deletion prior to the
      second active site Asp residue of the protease. RT-PCR experiments showed that
      the prtB gene is expressed, albeit at a low level.

PMID- 10882537
TI  - Statoliths in Phycomyces: characterization of octahedral protein crystals.
AB  - To identify the molecular mechanisms of gravitropism in the fungus Phycomyces
      blakesleeanus we determined several biochemical and physical parameters of
      paracrystalline protein bodies, so-called octahedral crystals. The crystals,
      which are present throughout the central vacuoles of the sporangiophore, function
      as statoliths (Schimek et al., 1999a,b). They possess an average volume of 9.96
      microm(3) and a specific mass of 1.26 g cm(-3). SDS-PAGE of purified crystals
      shows three major proteins with relative molecular masses of 16, 46.5, and 55
      kDa. These proteins are absent in gravitropism mutants which lack the crystals.
      Phototropism mutants (genotype mad) which are graviresponsive (class 1) and those
      which are defective in gravitropism (class 2) contain the crystals and the three
      associated proteins. Absorption spectra of isolated crystals and in situ
      absorption spectra of growing zones indicate the presence of chromophores,
      probably oxidized and reduced flavins. The flavin nature of the chromophores is
      also indicated by their fluorescence properties. It appears likely that the
      chromophores represent an essential part of the statoliths and thus the
      gravitropic transduction chain.

PMID- 10882538
TI  - Ernst knobil (1926-2000)

PMID- 10882539
TI  - Molecular pathogenesis of pituitary tumors.
AB  - Pituitary tumors are the result of a monoclonal outgrowth where the intrinsic
      genetic defects involve oncogenes, tumor suppressor genes (TSG), and most likely
      genes responsible for differentiation. In addition, hypothalamic and
      intrapituitary derived growth factors are imposed upon these aberrant cells,
      contributing to their growth characteristics. While histological examination will
      not identify those tumors likely to progress toward an invasive phenotype or
      those destined toward recurrence recent advances in the molecular pathology of
      these tumors holds significant promise for prediction of recurrence and the
      design of novel treatment strategies. Moreover, emerging data clearly indicate
      that different molecular mechanisms are involved in the pathogenesis of the
      various pituitary tumor subtypes. Until recently the gsp oncogene was the only
      oncogene significantly associated with pituitary tumors; however, emerging data
      have describe a role for PTTG and cyclin D1 in pituitary tumorigenesis. For known
      and putative TSG loci, allelic losses on the long arms of chromosomes 10, 11, and
      13 are significantly associated with the transition from the noninvasive to the
      invasive and metastatic phenotype, while losses on chromosome 9p occur early in
      pituitary tumorigenesis. Studies of known TSG at these loci, including the menin
      gene and RB1, would suggest a limited role, if any, in pituitary tumors. However,
      loss of pRB is evident in a proportion of somatotropinomas but is not associated
      with allelic loss of an RB1 intragenic marker. The gene encoding p16/CDKN2A is
      neither deleted nor mutated in pituitary tumors; however, its associated CpG
      island is frequently methylated and is associated with a loss of p16 protein
      expression. Allelic losses on chromosome 9p, frequent methylation, and loss of
      p16 protein appear as early changes in nonfunctional tumors, whereas they are
      infrequent events in somatotropinomas. The functional consequence of enforced
      expression of p16/CDKN2A in the mouse corticotroph cell line AtT20 has shown that
      it is responsible for a profound reduction in cell proliferation and the
      mechanism is a G(1) arrest, mimicking the in vivo role of this cell cycle
      regulator in most tissues. The combined data from several groups show that the
      allelic losses reported at known TSG loci are not accompanied by mutation in the
      retained allele. However, since abnormal methylation patterns may precede and
      predispose toward genetic instability this could account for the allelic losses
      on these chromosomes. Equally, since DNA methylation may lead to reduced
      expression of a gene it might also account for the reduced expression of as yet
      unidentified TSGs implicated in pituitary tumorigenesis. Collectively these
      studies hold significant promise as markers predictive of tumor behavior and
      point to novel treatment strategies, which may include the reactivation of TSGs
      that are intact but silenced through epigenetic mechanisms.

PMID- 10882540
TI  - VGF: a novel role for this neuronal and neuroendocrine polypeptide in the
      regulation of energy balance.
AB  - Insight into the mechanisms of action of neurotrophic growth factors has been
      obtained through the identification and characterization of gene products that
      are regulated or modified at the transcriptional, translational, and/or
      posttranslational level in response to neurotrophin treatment. VGF (non
      acronymic) was identified approximately 15 years ago as a nerve growth factor
      (NGF)-regulated transcript in rat PC12 pheochromocytoma cells. Subsequent studies
      have demonstrated that neurotrophins such as NGF and brain-derived neurotrophic
      factor induce vgf gene expression relatively rapidly in PC12 cells and cultured
      cortical neurons, respectively, in comparison to less robust regulation by
      epidermal growth factor (EGF) and insulin, growth factors which do not trigger
      the neuronal differentiation of PC12 cells. vgf gene expression is stimulated in
      vitro by NGF and the ras/map kinase signaling cascade through a CREB-dependent
      mechanism, while in vivo, VGF mRNA levels are regulated by neuronal activity,
      including long-term potentiation, seizure, and injury. Both the mRNA and encoded
      approximately 68-kDa protein (VGF) are selectively synthesized in neuroendocrine
      and neuronal cells. The predicted VGF sequence is rich in paired basic amino acid
      residues that are potential sites for proteolytic processing, and VGF undergoes
      regulated release from dense core secretory vesicles. Although VGF mRNA is
      synthesized widely, by neurons in the brain, spinal cord, and peripheral nervous
      system, its expression is particularly abundant in the hypothalamus. In addition,
      VGF peptides are found in hypophysial, adrenal medullary, gastrointestinal, and
      pancreatic endocrine cells, suggesting important neuroendocrine functions. Recent
      analysis of VGF knockout mice indeed demonstrates that VGF plays a critical role
      in the control of energy homeostasis. VGF knockout mice are thin, small,
      hypermetabolic, hyperactive, and relatively infertile, with markedly reduced
      leptin levels and fat stores and altered hypothalamic pro-opiomelanocortin,
      neuropeptide Y, and agouti-related peptide expression. Coupled with the
      demonstration that VGF mRNA levels are induced in the normal mouse hypothalamic
      arcuate nuclei in response to fasting, important central and peripheral roles for
      VGF in the regulation of metabolism are suggested. Here we review previous
      studies of VGF in the broader context of its newly recognized role in the control
      of energy balance and propose several models and experimental approaches that may
      better define the mechanisms of action of VGF.

PMID- 10882541
TI  - Neuroendocrine regulation of GnRH release in induced ovulators.
AB  - GnRH is the key neuropeptide controlling reproductive function in all vertebrate
      species. Two different neuroendocrine mechanisms have evolved among female
      mammals to regulate the mediobasal hypothalamic (MBH) release of GnRH leading to
      the preovulatory secretion of LH by the anterior pituitary gland. In females of
      spontaneously ovulating species, including rats, mice, guinea pigs, sheep,
      monkeys, and women, ovarian steroids secreted by maturing ovarian follicles
      induce a pulsatile pattern of GnRH release in the median eminence that, in turn,
      stimulates a preovulatory LH surge. In females of induced ovulating species,
      including rabbits, ferrets, cats, and camels, the preovulatory release of GnRH,
      and the resultant preovulatory LH surge, is induced by the receipt of genital
      somatosensory stimuli during mating. Induced ovulators generally do not show
      "spontaneous" steroid-induced LH surges during their reproductive cycles,
      suggesting that the positive feedback actions of steroid hormones on GnRH release
      are reduced or absent in these species. By contrast, mating-induced preovulatory
      surges occasionally occur in some spontaneously ovulating species. Most research
      in the field of GnRH neurobiology has been performed using spontaneous ovulators
      including rat, guinea pig, sheep, and rhesus monkey. This review summarizes the
      literature concerning the neuroendocrine mechanisms controlling GnRH biosynthesis
      and release in females of several induced ovulating species, and whenever
      possible it contrasts the results with those obtained for spontaneously ovulating
      species. It also considers the adaptive, evolutionary benefits and disadvantages
      of each type of ovulatory control mechanism. In females of induced ovulating
      species estradiol acts in the brain to induce aspects of proceptive and receptive
      sexual behavior. The primary mechanism involved in the preovulatory release of
      GnRH among induced ovulators involves the activation of midbrain and brainstem
      noradrenergic neurons in response to genital-somatosensory signals generated by
      receipt of an intromission from a male during mating. These noradrenergic neurons
      project to the MBH and, when activated, promote the release of GnRH from nerve
      terminals in the median eminence. In contrast to spontaneous ovulators, there is
      little evidence that endogenous opioid peptides normally inhibit MBH GnRH release
      among induced ovulators. Instead, the neural signals that induce a preovulatory
      LH surge in these species seem to be primarily excitatory. A complete
      understanding of the neuroendocrine control of ovulation will only be achieved in
      the future by comparative studies of several animal model systems in which mating
      induced as well as spontaneous, hormonally stimulated activation of GnRH neurons
      drives the preovulatory LH surge.

PMID- 10882542
TI  - Leptin regulation of neuroendocrine systems.
AB  - The discovery of leptin has enhanced understanding of the interrelationship
      between adipose energy stores and neuronal circuits in the brain involved in
      energy balance and regulation of the neuroendocrine axis. Leptin levels are
      dependent on the status of fat stores as well as changes in energy balance as a
      result of fasting and overfeeding. Although leptin was initially thought to serve
      mainly as an anti-satiety hormone, recent studies have shown that it mediates the
      adaptation to fasting. Furthermore, leptin has been implicated in the regulation
      of the reproductive, thyroid, growth hormone, and adrenal axes, independent of
      its role in energy balance. Although it is widely known that leptin acts on
      hypothalamic neuronal targets to regulate energy balance and neuroendocrine
      function, the specific neuronal populations mediating leptin action on feeding
      behavior and autonomic and neuroendocrine function are not well understood. In
      this review, we have discussed how leptin engages arcuate hypothalamic neurons
      expressing putative orexigenic peptides, e.g., neuropeptide Y and agouti
      regulated peptide, and anorexigenic peptides, e.g., pro-opiomelanocortin
      (precursor of alpha-melanocyte-stimulating hormone) and cocaine- and amphetamine
      regulated transcript. We show that leptin's effects on energy balance and the
      neuroendocrine axis are mediated by projections to other hypothalamic nuclei,
      e.g., paraventricular, lateral, and perifornical areas, as well as other sites in
      the brainstem, spinal cord, and cortical and subcortical regions.

PMID- 10882543
TI  - Partial characterization of a putative allatostatin receptor in the midgut of the
      cockroach Diploptera punctata.
AB  - Dippu-allatostatins (Dippu-ASTs) are a family of peptides originally isolated
      from the cockroach Diploptera punctata which appear to be pleiotropic in
      function. All members of the family are able to inhibit the biosynthesis of
      juvenile hormone by corpora allata in vitro. In addition, ASTs are able to
      modulate the contraction of visceral muscles and may play a role in the
      regulation of digestive enzyme secretion by the midgut. We have identified a
      putative AST receptor in the cockroach midgut using a radioligand-binding assay.
      (125)I-Dippu-AST 7 binding to midgut membranes was specific, saturable, and
      reversible. The midgut appears to contain a single class of binding sites for
      Dippu-AST 7, with K(d) of 20.9 +/- 3.6 nM and B(max) of 1.8 +/- 0.15 pmol. mg(-1)
      membrane protein. The relative affinity of the 13 members of the Dippu-AST family
      was determined using a single-point competitive binding assay. Dippu-AST 7 and 2
      appear to have higher affinity for the midgut AST receptor than Dippu-AST 5, 9,
      10, or 11. Other Dippu-ASTs were unable to compete with (125)I-Dippu-AST 7 for
      binding, even at high concentration.

PMID- 10882544
TI  - PCNA in the testis of the frog, Rana esculenta: a molecular marker of the mitotic
      testicular epithelium proliferation.
AB  - Proliferating cell nuclear antigen (PCNA) plays an essential role in nucleic acid
      metabolism as a component of the replication and repair machinery. This toroidal
      shaped protein encircles DNA and can slide bidirectionally along the duplex. One
      of the well-established functions for PCNA is its role as the processing factor
      for DNA polymerase delta and epsilon. It has become apparent that PCNA interacts
      with proteins involved in the cell cycle. The PCNA interactions with different
      cellular proteins and the importance of these interactions are also discussed. To
      examine the different mitotic testicular epithelium proliferation during the
      annual discontinuous frog (Rana esculenta) spermatogenesis, the temporal and the
      spatial PCNA expression are described and give a useful endogenous molecular
      marker.

PMID- 10882545
TI  - Photoperiod regulation of plasma growth hormone levels during induced
      smoltification of underyearling Atlantic salmon.
AB  - Earlier studies have established that increased daylength increases plasma growth
      hormone (GH) levels during spring smoltification of yearling Atlantic salmon.
      Recently, the Atlantic salmon aquaculture industry has started the production of
      underyearling ("summer") smolts. This involves fast juvenile growth on continuous
      light (24L), the transfer of juveniles over 8 cm in length to short day (12L) for
      6 weeks in the summer, followed by transfer to 24L for another 6 weeks before
      transfer to seawater in late October. Three groups were studied in fresh water
      from July to the following May in order to elucidate the GH response to this
      photoperiod manipulation: one group was kept on 24L throughout (long-day group),
      while the other two groups were exposed to short day from July 15th. Of these,
      one was brought back onto long day on September 1st (winter group) while the
      other was kept on short day (short-day group). Plasma GH levels of the long-day
      group were around 1.6 ng/ml throughout the study. The short-day transfer
      suppressed GH levels to 0.7 ng/ml within 2 weeks (short-day and winter groups).
      The long-day transfer (winter group) increased GH levels to 11 ng/ml within 3
      weeks, and this elevation of GH levels was sustained for about 3 months, before
      declining to pretreatment levels. The study demonstrates that underyearling
      Atlantic salmon react to increased daylength in a way similar to traditional
      yearling smolts. It also demonstrates for the first time that decreased daylength
      can suppress plasma GH levels in fish. It is concluded that winter photoperiod
      manipulation causes an out-of-season initiation and completion of the parr-smolt
      transformation of underyearling Atlantic salmon and that growth hormone plays a
      major role in this process.

PMID- 10882546
TI  - Comparison of extraction methods and assay validation for salmon insulin-like
      growth factor-I using commercially available components.
AB  - Insulin-like growth factor-binding proteins (IGFBPs) may interfere with accurate
      measurement of plasma IGFs in radioimmunoassay (RIA). Although several simplified
      extraction methods for IGFs have been developed, these methods are not always
      validated for differing physiological states, developmental stages, and animal
      species. For teleost fish, neither the necessity of plasma extraction nor the
      validity of extraction methods for IGF RIA is widely established. We
      systematically examined the validity of acid-ethanol (AE) extraction, AE
      extraction followed by cryoprecipitation (AEC extraction), and SP-Sephadex
      extraction in RIA for salmon IGF-I using commercially available components
      (GroPep Pty Ltd). Displacement curves of plasma extracted by AE, AEC, and SP
      Sephadex were parallel to those of the standard. Measured IGF-I levels in plasma
      from several developmental stages and under different physiological and
      experimental conditions were significantly increased by the extractions and
      comparable to those after acid-size exclusion chromatography (SEC). On Western
      ligand blotting using digoxigenin-labeled human IGF-I, the intensity of IGFBP
      bands remaining in plasma were reduced after extraction, although some IGFBPs
      remained. However, these residual IGFBPs did not interfere measurably with the
      RIA based on quantitative comparison of IGF-I levels with acid-SEC. We conclude
      that with this RIA extraction is necessary for measurement of salmon IGF-I in
      plasma since measured values were routinely lower in unextracted samples, and AE,
      AEC, and SP-Sephadex extractions are applicable to the IGF-I RIA using the
      commercially available components. Using the validated RIA for IGF-I, plasma IGF
      I levels in nonmaturing and precociously maturing chinook salmon in spring were
      measured after AE extraction. During spring, nonmaturing and maturing fish fed
      and grew well, and plasma IGF-I level was significantly correlated with body
      weight in both fish. This result indicates that circulating IGF-I plays a key
      role in controlling growth in precociously maturing chinook salmon in spring as
      in nonmaturing fish.

PMID- 10882547
TI  - Differentiating ability of the pars intermedia in hypothalectomized frog
      tadpoles.
AB  - It is generally accepted that hypothalectomy of frog tadpoles at the open neurula
      stage results in failure of the pars intermedia to develop. A pale body color is
      assumed to be evidence that the hypothalamus was completely removed. The present
      study, however, shows that hypothalectomized Rana japonica can develop into
      either albino, as already reported, or darkly pigmented tadpoles. In order to
      determine the extent to which the intermediate lobe can develop in these
      hypothalectomized tadpoles, their adenohypophyses were examined
      immunohistochemically by using anti-alphaMSH (melanocyte-stimulating hormone). In
      all the dark-colored larvae a pars intermedia had formed, though its size was
      very small. In the pale-colored tadpoles, on the other hand, the pars intermedia
      frequently failed to differentiate, but it was observed in 4 of 13
      hypothalectomized larvae. In view of other investigators' data showing the
      complete absence of ACTH (adrenocorticotropin) cells in hypothalectomized
      tadpoles, hypophyses were also stained with anti-ACTH. Immunoreactive ACTH cells
      were detected in hypothalectomized tadpoles irrespective of the body
      pigmentation, although their incidence was lower than in normal controls. These
      data indicate that contact between the infundibulum and adenohypophysis is not
      absolutely essential for differentiation of MSH and ACTH cells in the frog.

PMID- 10882548
TI  - Seasonal variation in reproductive steroids of male and female yellow-blotched
      map turtles, Graptemys flavimaculata.
AB  - From April to October of 1996 and 1997, we measured seasonal changes in plasma
      testosterone (T) in male and plasma T and estradiol-17beta (E(2)) in female
      yellow-blotched map turtles, Graptemys flavimaculata, from the Pascagoula River,
      Mississippi. In 1996, plasma from females was analyzed for progesterone. In 1997,
      ovaries of adult females were ultrasound imaged to determine stages of follicular
      development. Males exhibited peak T levels in September and October of both
      years, indicating fall gonadal activity. Males also exhibited a low level spring
      peak in T during April. Female E(2) levels increased significantly in May and
      June, the primary period of ovarian development. Females with preovulatory
      follicles did not have significantly higher E(2) levels than females with medium-
      or small-sized follicles. When compared to other freshwater turtle species, peak
      levels of E(2) were low. Testosterone levels did not follow a distinct yearly
      pattern in females. Progesterone levels were elevated in June when peak nesting
      was observed. Ultrasound and hormone data indicate that females lack ovarian
      development in the fall and produce on average only one clutch per year.

PMID- 10882549
TI  - Daily and seasonal variation in response to stress in captive starlings (Sturnus
      vulgaris): corticosterone.
AB  - Captive starlings were used to examine daily and seasonal changes in basal and
      stress-induced corticosterone levels. Birds were bled at 4 times during the daily
      cycle and during three different simulated seasons: under a short-day photoperiod
      (mimicking winter), under a long-day photoperiod (mimicking summer), and while
      undergoing a prebasic molt. Basal corticosterone samples were assayed from blood
      collected within 3 min of disturbance and corticosterone increases in response to
      handling and restraint were monitored in blood taken at 15, 30, and 45 min
      postdisturbance. Handling and restraint elicited robust increases in
      corticosterone at all times of the day and during all three seasons. Both basal
      and stress-induced levels varied with the time of day (with the exception of
      basal samples during molt). Levels were higher at night, during the bird's
      inactive period, and decreased during the day. These data indicate that starlings
      have daily rhythms in both basal corticosterone levels and in their response to
      stress, with more corticosterone released during the night in response to
      identical stimuli. Starlings also show pronounced seasonal variation in both
      basal and stress-induced corticosterone levels. Although birds held on short and
      long days had equivalent corticosterone levels, both basal and stress-induced
      levels were lower during molt. This parallels data from free-living birds and
      provides a laboratory model for studying seasonal corticosterone regulation.

PMID- 10882550
TI  - Daily and seasonal variation in response to stress in captive starlings (Sturnus
      vulgaris): glucose.
AB  - We investigated the seasonal and daily variation in plasma glucose levels in
      response to stress in captive wild starlings. Starlings were captured from the
      wild during the winter, held on short days (11L:13D, mimicking winter), and then
      shifted to long days (19L:5D, mimicking summer). Birds were maintained on long
      days until they began a prebasic molt, the energetically costly replacement of
      feathers. Throughout the daily cycle we took a basal blood sample within 3 min of
      disturbance and took subsequent blood samples at 15 and 30 min. Birds were kept
      in cloth bags (restraint) between bleeds. Experiments were repeated during all
      three seasons (short day, long day, and molt). Starlings showed no sexual
      difference in circulating glucose levels at any time of the day or in any season.
      Both basal and stress-induced glucose levels, however, showed a significant
      effect of season, with birds held on long days exhibiting the highest levels,
      molting birds showing intermediate levels, and birds held on short days
      exhibiting the lowest levels. Basal glucose levels also showed a circadiel rhythm
      in all three seasons. Regardless of season, however, the daily peak in basal
      levels occurred at midday with nadir in the middle of the scotophase. This trend
      was paralleled in the overall weights of the birds. Although stress-induced
      glucose levels showed no circadiel rhythm, the stress-induced elevation of
      glucose above baseline showed a significant daily rhythm, indicating that stress
      elevated plasma glucose levels only during the scotophase in all three seasons.

PMID- 10882551
TI  - Aluminium and cadmium inhibit vitellogenin and its mRNA induction by estradiol-17
      beta in the primary culture of hepatocytes in the rainbow trout Oncorhynchus
      mykiss.
AB  - Effects of Al and Cd on vitellogenin (VTG) and VTG mRNA induction by estradiol-17
      beta (E(2)) were examined in primary hepatocyte cultures of rainbow trout.
      Hepatocytes were precultured for 2 days and then E(2) (2 x 10(-6) M) and Al (10(
      6)-10(-4) M) or Cd (10(-9)-10(-6) M) were simultaneously added to the incubation
      medium. Hepatocytes were cultured for 5 more days. Media and hepatocytes were
      then analyzed by SDS-PAGE and Northern blotting for VTG and VTG mRNA,
      respectively. These metals had no appreciable effect on the viability of
      hepatocytes in culture. However, Al and Cd interfered with VTG production and VTG
      mRNA expression. Al reduced VTG production in a concentration-dependent way and a
      significant reduction occurred at Al concentrations greater than 5 x 10(-5) M.
      VTG mRNA expression also decreased with a negative correlation with Al
      concentrations (r = -0.98). The inhibition of VTG production by Cd was not
      concentration-dependent. This metal markedly inhibited VTG production and VTG
      mRNA expression at 10(-6) M. The Al-induced inhibition of VTG production was
      restored 7 days after Al removal, but the Cd-induced inhibition was not restored.
      These results suggest that Al and Cd inhibit VTG production at the
      transcriptional level to reduce VTG mRNA expression by different mechanisms.

PMID- 10882552
TI  - Cloning of pro-vasotocin and pro-isotocin cDNAs from the flounder Platichthys
      flesus; levels of hypothalamic mRNA following acute osmotic challenge.
AB  - Sequences coding for pro-vasotocin and pro-isotocin have been identified by
      screening a flounder (Platichthys flesus) hypothalamic cDNA library. The 1074-bp
      proVT and 727-bp proIT sequences contain a signal peptide and hormone, connected
      to a neurophysin by a Gly-Lys-Arg sequence. Both sequences also have an elongated
      carboxyl-terminal with a leucine-rich core resembling copeptin but lacking the
      amino terminal Arg residue. The levels of pro-vasotocin and pro-isotocin mRNA in
      the hypothalamus were measured concomitantly with pituitary AVT content and
      plasma AVT concentration following acute transfer of fish between freshwater and
      seawater. Three days after transfer from seawater to freshwater there appears to
      be a down regulation of the AVT hormone system with a fall in hypothalamic pro
      vasotocin mRNA levels, an increase in pituitary AVT content, and a fall in plasma
      levels, but these changes did not achieve statistical significance compared to
      controls. No change in the AVT system was detected 3 days following the transfer
      of fish from freshwater to seawater. Hypothalamic isotocin mRNA levels did not
      change following hypo- or hyperosmotic challenge.

PMID- 10882554
TI  - Effects of lighting conditions and melatonin supplementation on the cellular and
      humoral immune responses in Japanese quail Coturnix coturnix japonica.
AB  - Two experiments were conducted to determine the effects of lighting conditions
      and melatonin supplementation on the cellular and humoral immune responses in
      Japanese quail. The first experiment was designed to evaluate differing light
      regimes as immune modulators in both adult and juvenile quail. The cellular and
      humoral immune responses were determined for three lighting conditions; short
      days (8:16LD), long days (16:8LD), and constant light (LL). In the second
      experiment, melatonin was administered in varying doses to adult quail placed in
      LL. The doses used in this experiment were 0.0, 0.5, 5.0, and 50.0 microg/ml
      melatonin given in the drinking water for 16 h per day for 2 weeks. The cellular
      and humoral immune responses were evaluated after 1 week of melatonin treatment.
      In both experiments, a cutaneous basophil hypersensitivity reaction to
      phytohemagglutinin (PHA-P) was measured to evaluate the cellular immune response.
      To evaluate the humoral immune response, primary antibody titers were calculated
      7 days postintravenous injection with a Chukar red blood cell suspension. In the
      adult birds of experiment 1, both the 8:16LD and 16:8LD treatments produced
      similar cellular and humoral immune responses but these responses were
      significantly greater than those observed in LL. The juvenile birds held under
      8:16LD also had significantly greater cellular and humoral immune responses as
      compared to juvenile birds held in LL. In experiment 2, there was a clear
      melatonin dose response on immune function in LL. The humoral immune response
      increased to a peak at the 5.0 microg/ml dose while the cellular immune response
      increased across all dose levels. From the present study it was clear that quail
      placed in daily light-dark cycles (LD), possessing a diurnal rhythm of melatonin,
      had significantly elevated immune responses as compared to those birds in LL.
      Furthermore, melatonin supplemented to birds exposed to LL was immuno-enhancing.
      This suggests that melatonin may be a mediator of the differences seen between LD
      and LL lighting conditions and may have important immune modulating properties.

PMID- 10882553
TI  - Islet hormones from the African bullfrog Pyxicephalus adspersus (Anura:Ranidae):
      structural characterization and phylogenetic implications.
AB  - The African bullfrog Pyxicephalus adspersus is generally classified along with
      frogs of the genus Rana in the subfamily Raninae of the family Ranidae but
      precise phylogenetic relationships between species are unclear. Pancreatic
      polypeptide (PP), insulin, and glucagon-like peptide (GLP-1) were isolated from
      an extract of P. adspersus pancreas and characterized structurally. A comparison
      of the amino acid sequence of Pyxicephalus PP
      (APSEPQHPGG(10)QATPEQLAQY(20)YSDLYQYITF(30)ITRPRF++ +. NH(2)) with those of the
      known amphibian PP molecules in a maximum parsimony analysis generates a single
      phylogenetic tree in which Pyxicephalus is the sister to the clade comprising the
      members of the genus Rana. The three orders of living amphibians form discrete
      clades with the representative of the Gymnophiona appearing as sister to the
      Caudata-Anura. In contrast, Pyxicephalus insulin (A chain,
      GIVEQCCHSA(10)CSLYDLENYC(20)N; B-chain,
      LANQHLCGSH(10)LVEALYMVCG(20)ERGFFYYPKS(30)) and and GLP-1
      (HAEGTFTSDM(10)TSYLEEKAAK(20)EFVDWLIKGR(30)PK) resemble more closely the
      corresponding peptides from the cane toad Bufo marinus than the peptides from any
      species of Rana. Cladistic analysis based upon the amino acid sequences of
      insulin produced a polyphyletic assemblage with the Gymnophiona nesting within an
      unresolved clade containing the non-ranid frogs. The data support the assertion
      that the amino acid sequence of PP, but not those of the other islet hormones, is
      of value as a molecular marker for inferring phylogenetic relationships between
      early tetrapod species.

PMID- 10882555
TI  - In vitro effects of estradiol and aromatase inhibitor treatment on sex
      differentiation in Xenopus laevis gonads.
AB  - Gonads, still in the indifferent stage, were taken from tadpoles of Xenopus
      laevis and maintained in organ culture. These gonads were kept in good condition
      by frequent replacement of the culture medium and then underwent sexual
      differentiation. When the indifferent gonads were cultured in estradiol for 14
      days, 90% of the explants showed female histological characteristics. The
      estradiol treatment of gonads in vitro gave results identical to those obtained
      from tadpoles treated in vivo. The gonads of X. laevis were successfully
      maintained for 14 days in vitro in a medium containing 20 microg/ml aromatase
      inhibitor (CGS 16949A). All the gonads treated with aromatase inhibitor showed
      the histological characteristics of the male phenotype. These results suggest
      that estradiol is important for ovarian differentiation in X. laevis.

PMID- 10882556
TI  - Profiles of gonadal development, sex steroids, aromatase activity, and
      gonadotropin II in the controlled sex change of protandrous black porgy,
      Acanthopagrus schlegeli Bleeker.
AB  - The objectives of the present study were to investigate the effects of oral
      administration of estradiol-17 beta (E(2)) on the sex steroids and gonadotropin
      II (GTH II) in plasma, aromatase activity in gonad and brain, and sex change in
      protandrous black porgy, Acanthopagus schlegeli Bleeker. Two-year-old black porgy
      were divided into two groups, one fed a control diet and the other a diet mixed
      with E(2) (4.0 mg/kg feed) for 7 months. Significantly higher GSI was observed in
      the E(2) group. Fish treated with E(2) showed complete suppression of
      spermatogenesis and spermiation and induced sex change with vitellogenic oocytes
      and large primary oocytes. Lower levels of plasma 11-ketotestosterone and higher
      levels of plasma vitellogenin were shown in the E(2) group. Higher gonadal
      aromatase activity in concordance with elevated plasma levels of GTH II was
      observed in the E(2) group. The highest aromatase activity in the forebrain in
      the control group was observed in January. Higher aromatase activity in
      forebrain, midbrain, and hindbrain was also detected in the E(2) group than the
      control group. The change of aromatase activity in brain was more susceptible
      than that in gonad. The data showed that the increase of plasma GTH II levels and
      gonadal aromatase activity may be important to the controlled sex change by
      administration in black porgy.

PMID- 10882557
TI  - Process heterochronies in endochondral ossification.
AB  - Heterochrony, evolutionary changes in developmental rates and timing, is a key
      concept in the construction of a synthesis of development and evolution.
      Heterochronic changes in vertebrate evolution have traditionally been identified
      through plesiomorphic-apomorphic comparisons of bone growth. This methodological
      framework assumes that observed heterochronies are the outcome of dissociations
      of developmental processes in time. Recent findings of non-heterochronic
      developmental changes underlying morphological heterochrony invalidate this
      assumption. In this paper, a function for bone growth (at the organ level) has
      been mathematically deduced from the underlying developmental mechanisms. The
      temporal domain of the model spans from the time at maximum growth rate, after
      the formation of growth plates, to the time at atrophy of the proliferating
      stratum of cells. Three organizational levels were considered: (a) cell kinetics
      of endochondral ossification, (b) variation of bone growth rates and (c)
      variation of accumulated bone growth with increasing age. This quantitative model
      provides an excellent tool to deal with the problem of the developmental basis of
      morphological change. I have modelled potential evolutionary changes on the
      system at different levels of biological organization. This new framework
      involves an epistemological shift in heterochronic analysis from a pattern
      oriented inductive way to a process-oriented deductive way. The analysis of the
      relationships between the evolutionary alterations of endochondral ossification
      and the morphological expression of these changes reveals that observed pattern
      heterochronies can be the outcome of different process heterochronies. Moreover,
      I discuss at length the heteroposic hypothesis, that evolutionary changes in the
      tight regulation of the amount of protein synthesized by a cell population during
      development would underlie acceleration or deceleration in cases of evolutionary
      changes in the initial number of proliferating cells at growth plates. Future
      research on the genetic basis of process heterochronies and heteroposies will
      complete our understanding of these evolutionary phenomena.

PMID- 10882558
TI  - Insulin receptor binding kinetics: modeling and simulation studies.
AB  - Biological actions of insulin regulate glucose metabolism and other essential
      physiological functions. Binding of insulin to its cell surface receptor
      initiates signal transduction pathways that mediate cellular responses. Thus, it
      is of great interest to understand the mechanisms underlying insulin receptor
      binding kinetics. Interestingly, negative cooperative interactions are observed
      at high insulin concentrations while positive cooperativity may be present at low
      insulin concentrations. Clearly, insulin receptor binding kinetics cannot be
      simply explained by a classical bimolecular reaction. Mature insulin receptors
      have a dimeric structure capable of binding two molecules of insulin. The binding
      affinity of the receptor for the second insulin molecule is significantly lower
      than for the first bound insulin molecule. In addition, insulin receptor
      aggregation occurs in response to ligand binding and aggregation may also
      influence binding kinetics. In this study, we develop a mathematical model for
      insulin receptor binding kinetics that explicitly represents the divalent nature
      of the insulin receptor and incorporates receptor aggregation into the kinetic
      model. Model parameters are based upon published data where available. Computer
      simulations with our model are capable of reproducing both negative and positive
      cooperativity at the appropriate insulin concentrations. This model may be a
      useful tool for helping to understand the mechanisms underlying insulin receptor
      binding and the coupling of receptor binding to downstream signaling events.

PMID- 10882559
TI  - Phylogenetic invariants and geometry.
AB  - The method of invariants is an important approach in biology for determining
      phylogenetic information which avoids the problems involving long branch lengths
      that plague some other methods. In this paper, we present a geometric framework
      underlying the method of invariants. This perspective sheds new lights on
      problems in the field. It has recently enabled the solution of questions on the
      number and structure of phylogenetic invariants and suggests possible avenues for
      future empirical and theoretical research.

PMID- 10882560
TI  - Planktonic contact rates in homogeneous isotropic turbulence: theoretical
      predictions and kinematic simulations.
AB  - The key role played by turbulence in the environment of plankton and larval fish
      populations has become appreciated in recent years. In particular, the turbulent
      enhancement of encounter rates between different species of microorganisms,
      either swimming or passively advected by the flow, is well established. However,
      most of the current modelling approaches are rather ad hoc, giving rise to
      ambiguities in the specification of certain key parameters. In this paper, the
      encounter problem in a turbulent flow of large Reynolds number is re-examined
      from first principles and a number of new formulae will be established for
      different swimming strategies. The key innovation is the proposal of a model form
      for the conditional joint probability density function of predator and prey
      velocities when the organisms are separated by their given contact radius, R.
      Particular attention will be paid to the case when a microorganism follows a
      random trajectory, due to a combination of its own swimming and the action of the
      flow. The theoretical predictions are subsequently tested against corresponding
      quantities derived from a series of kinematic simulations of a turbulent-like
      flow field. Good agreement is demonstrated between the predictions and
      simulations.

PMID- 10882561
TI  - Molecular evolution of catalysis.
AB  - In this paper, we consider the evolutionary dynamics of catalytically active
      species with a distinct genotype-phenotype relationship. Folding landscapes of
      RNA molecules serve as a paradigm for this relationship with essential neutral
      properties. The landscape itself is partitioned by phenotypes (realized as RNA
      secondary structures). To each genotype (represented as a sequence) a structure
      is assigned in a unique way. The set of all sequences which map into a particular
      structure is modeled as a random graph in sequence space (the so-called neutral
      network). A catalytic network is realized as a random digraph with maximal out
      degree two and secondary structures as vertex sets. A population of catalytic RNA
      molecules shows significantly different behavior compared to a deterministic
      description: hypercycles are able to co-exist and out-compete a parasite with
      superior catalytic support. A "switching" between different dynamic organizations
      of the network can be observed, dynamical stability of hypercyclic organizations
      against errors and the existence of an error-threshold of catalysis can be
      reported.

PMID- 10882562
TI  - Self-synchronization and task fulfilment in ant colonies.
AB  - Some authors have hypothesized that the observed self-synchronized activity in
      ant colonies provides some adaptive advantages, and, in particular, it has been
      suggested that task realization may benefit from this ordered temporal pattern of
      behaviour (Robinson, 1992, Ann. Rev. Entomol, 37, 637-702; Hatcher et al., 1992,
      Naturwissenschaften, 79, 32-34). In this paper, we use a model of self
      synchronized activity (the fluid neural network) to suggest that with self
      synchronized patterns of activity a task may be fulfiled more effectively than
      with non-synchronized activity, at the same average level of activity per
      individual.

PMID- 10882563
TI  - Interpreting the distortion associated with a retinal wholemount.
AB  - Wholemounting is a standard procedure used to view the retinal organization in
      light microscopic studies. Radial cuts are made into the retina from its
      perimeter to allow it to be flattened onto a glass slide. This process distorts
      the retina and introduces missing pie (phantom) sectors into the wholemount.
      Distortion in the retinal wholemount has been quantified by modeling the retina
      as a hemisphere transformed into a disc interrupted with phantom sectors. The
      interrupted continuity of the retinal wholemount indicates that an angle
      subtended at the center of the wholemount must be smaller than its corresponding
      angle in the intact retina. In the model presented here (H-D transform) a method
      is described for interconverting angles between the hemisphere and the wholemount
      and for transforming any point on the wholemount back onto the surface of the
      hemisphere. Computations on the model show that the angles, subtended by phantom
      sectors at the center of a wholemounted retina, on a given concentric circle can
      be quantified and summed to a constant value. The value depends on and
      monotonically increases with eccentricity, it is nil at the center of the
      wholemount and maximal at the retinal margin. As a result, radial cuts made in
      the periphery of the wholemount need not extend into its center. In addition,
      sector edges of the wholemount are approximated by quarter wave sinusoids, larger
      sectors having greater amplitude and consequently greater distortion. Moreover, a
      large piece of tissue exerts more spring recoil and thus in large retinas
      relatively more cuts are required in the wholemount. However, the total angle
      deficit of the phantom sectors around the circumference of the wholemount is
      unaffected by the radius of the eye. A standard configuration for the wholemount
      is defined that minimizes the overall error in orientation for any sector.

PMID- 10882564
TI  - Modeling the interaction of peroxynitrite with low-density lipoproteins. I.
      Plasma levels of peroxynitrite.
AB  - Peroxynitrite is a strong candidate for the material responsible for the
      initiation of peroxidation of low-density lipoproteins (LDLs) which is considered
      the first step in the formation of atherosclerotic plaque. Recent advances in the
      understanding of peroxynitrite chemistry allow the construction of a kinetic
      model that can be used to understand the factors controlling levels in plasma.
      These results indicate that the carbon dioxide catalysed decomposition of
      peroxynitrite produces large quantities of reactive species, but the rapid
      decomposition of this intermediate, ONOOCO(-)(2), may limit its availability to
      attack LDLs at points distant from the site of production. In this case,
      peroxynitrite itself may be of greater quantitative importance in LDL
      peroxidation.

PMID- 10882565
TI  - Modeling the interaction of peroxynitrite with low-density lipoproteins. II:
      reaction/diffusion model of peroxynitrite in low-density lipoprotein particles.
AB  - Peroxynitrite is a possible initiator for the free radical chain reaction that
      results in peroxidation of low-density lipoproteins (LDL) which is the first step
      in atherogenisis. This paper reports on the use of a diffusion/reaction model to
      examine the processes involved in peroxynitrite attack on LDL particles. Results
      indicate that because of the short distance involved, diffusion is much more
      rapid than chemical decomposition. Because of this decoupling the free radicals
      generated by peroxynitrite decomposition may be found at any point in the LDL
      particle. At the concentrations expected in physiological systems only a small
      proportion of LDL particles may contain peroxynitrite molecules. However, these
      particles may still be profoundly effected because of the long reaction chain
      length expected after initiation.

PMID- 10882566
TI  - Modeling the interaction of peroxynitrite with low-density lipoproteins. III: the
      role of antioxidants.
AB  - Peroxynitrite is a candidate for the substance responsible for the initiation of
      peroxidation of low-density lipoproteins (LDL) in blood. This is believed to be
      the initial step in the formation of atherosclerotic plaque. Using kinetic
      arguments, this paper examines possible routes in both LDL particles and in the
      surrounding plasma for antioxidants to block peroxidation. The antioxidants
      considered include ascorbate ion, glutathione and human serum albumin in plasma
      as well as alpha -tocopherol, ubiquinone-10 and carotenoids in the LDL particles.
      The results suggest that in the plasma compartment the most efficacious blocking
      mechanism is the reaction of ascorbate ion with the peroxynitrite precursor,
      superoxide ion. The situation in LDL particles is much less clear cut because of
      the paucity of kinetic data in this medium. However, some constraints are
      suggested on the requirements for an effective antioxidant.

PMID- 10882567
TI  - Modeling DNA mutation and recombination for directed evolution experiments.
AB  - Directed evolution experiments rely on the cyclical application of mutagenesis,
      screening and amplification in a test tube. They have led to the creation of
      novel proteins for a wide range of applications. However, directed evolution
      currently requires an uncertain, typically large, number of labor intensive and
      expensive experimental cycles before proteins with improved function are
      identified. This paper introduces predictive models for quantifying the outcome
      of the experiments aiding in the setup of directed evolution for maximizing the
      chances of obtaining DNA sequences encoding enzymes with improved activities. Two
      methods of DNA manipulation are analysed: error-prone PCR and DNA recombination.
      Error-prone PCR is a DNA replication process that intentionally introduces
      copying errors by imposing mutagenic reaction conditions. The proposed model
      calculates the probability of producing a specific nucleotide sequence after a
      number of PCR cycles. DNA recombination methods rely on the mixing and
      concatenation of genetic material from a number of parent sequences. This paper
      focuses on modeling a specific DNA recombination protocol, DNA shuffling. Three
      aspects of the DNA shuffling procedure are modeled: the fragment size
      distribution after random fragmentation by DNase I, the assembly of DNA
      fragments, and the probability of assembling specific sequences or combinations
      of mutations. Results obtained with the proposed models compare favorably with
      experimental data.

PMID- 10882568
TI  - A clock and trail model for somite formation, specialization and polarization.
AB  - We present some theoretical considerations about the initial process of pre
      patterning during embryonic segmentation, with particular reference to somite
      formation. We first suggest that the pre-pattern is a stable spatial sinusoidal
      (or, at least, periodic) wave. The periodic wave originates from an oscillator
      ("clock") in the proliferative region that gives rise to the cells. At the moment
      the cells leave the proliferative or "progress" zone, or somewhat later, a
      permanent record is made of the current state of the oscillation, which cells
      then keep during their pre-somitic phase, before explicit somite and somite
      boundary formation. Thus, a trail is left behind the progress zone in the form of
      a spatial sine wave. Second, we also observe that the factors involved in the
      progress-zone clock and its wave-like trail may form multimers, which will
      oscillate with higher space-time frequency and thus shorter wavelengths than the
      monomers. Whether or not our first suggestion is correct, this phenomenon may
      account for multiple wavelengths in somitogenesis, and may thus encompass somite
      formation, but also somite polarization (half-wavelength) into anterior and
      posterior halves, as well as the puzzling observation that expression of her1 in
      zebrafish is in primordia of alternating somites, i.e. it exhibits a 2-somite
      wavelength.

PMID- 10882569
TI  - Whirled grain in wood and topological defects.

PMID- 10882570
TI  - The X chromosome and the rate of deleterious mutations in humans.
AB  - Monosomy for the X chromosome in humans creates a genetic Achilles' heel for
      nature to deal with. We report that the human X chromosome appears to have one
      third the density of the coding sequence of the autosomes and, because of partial
      shielding from the high mutation rate of the male sex, that it should also have a
      lower mutation rate than the autosomes (i.e.,.73). Hence, the X chromosome should
      contribute one quarter (.33x.73=.24) of the deleterious mutations expected from
      its DNA content. In this way, selection has possibly moderated risks from
      mutation in X-linked genes that are thought to have been fixed in their syntenic
      state since the onset of the mammalian lineage. The unexpected difference in the
      density of coding sequences indicates that our recent, hemophilia B-based
      estimate of the rate of deleterious mutations per zygote should be increased from
      1.3 to 4 (1.3x3).

PMID- 10882572
TI  - Statement on Gene Therapy, April 2000.

PMID- 10882571
TI  - Linkage of tuberculosis to chromosome 2q35 loci, including NRAMP1, in a large
      aboriginal Canadian family.
AB  - An epidemic of tuberculosis occurred in a community of Aboriginal Canadians
      during the period 1987-89. Genetic and epidemiologic data were collected on an
      extended family from this community, and the evidence for linkage to NRAMP1, a
      candidate gene for susceptibility to mycobacterial diseases, was assessed.
      Individuals were grouped into risk (liability) classes based on vaccination, age,
      previous disease, and tuberculin skin-test results. Under the assumption of a
      dominant mode of inheritance and a relative risk of 10, which is associated with
      the high-risk genotypes, a maximum LOD score of 3.81 was observed for linkage
      between a tuberculosis-susceptibility locus and D2S424, which is located just
      distal to NRAMP1, in chromosome region 2q35. Significant linkage was also
      observed between a tuberculosis-susceptibility locus and a haplotype of 10 NRAMP1
      intragenic variants. No linkage to the major histocompatibility-complex region on
      chromosome 6p was observed, despite distortion of transmission from one member of
      the oldest couple to their affected offspring. The ability to assign individuals
      to risk classes was crucial to the success of this study.

PMID- 10882573
TI  - Genetic predisposition to clinical tuberculosis: bridging the gap between simple
      and complex inheritance.

PMID- 10882574
TI  - Poliovirus-specific intestinal antibody responses coincide with decline of
      poliovirus excretion.
AB  - Antibody responses to poliovirus type 3 were studied in fecal samples of 66
      children immunized with 3 doses of enhanced-potency inactivated poliovirus
      vaccine (E-IPV), followed by 1 dose of monovalent oral poliovirus vaccine (OPV,
      type 3 Sabin). One fecal sample taken before OPV vaccination and 9 collected
      thereafter were tested for neutralizing antibodies by a microneutralization assay
      and for class-specific responses by heavy chain-capture radioimmunoassays. Both
      neutralizing antibody and IgA responses usually occurred during the second week
      and coincided with ceasing of virus excretion or a decrease in the excreted virus
      titer. Half of the vaccinees had received a trypsin-modified E-IPV, but their
      responses did not differ from those of children immunized with the regular E-IPV.
      These results are in agreement with the view that an intestinal antibody
      response, mainly consisting of IgA, may be involved in the ceasing of a primary
      poliovirus excretion.

PMID- 10882575
TI  - Widespread paralytic poliomyelitis in Pakistan: A case-control study to determine
      risk factors and implications for poliomyelitis eradication.
AB  - Despite substantial efforts to eradicate poliomyelitis by administering oral
      poliovirus vaccine through routine immunization and annual national immunization
      days (NIDs), Pakistan reported 22% (1147) of the worldwide cases in 1997. Reasons
      for continued high poliomyelitis incidence include failure to vaccinate, vaccine
      failure, or inadequate immunization strategies. A case-control study was
      conducted to measure vaccination status and reasons for undervaccination among 66
      poliomyelitis cases and 130 age- and neighborhood-matched controls. Cases were
      undervaccinated through routine immunization (matched odds ratio [MOR], 0.3; 95%
      confidence interval [CI], 0.1-0.5); however, NID immunization was similar for
      cases and controls (MOR, 0.6; 95% CI, 0.3-1.2). Reasons for undervaccination
      included not being informed, considering vaccination unimportant, and long
      distances to vaccination sites. Failure to vaccinate through routine immunization
      was a major risk factor for poliomyelitis in Pakistan. Successful NIDs alone will
      not interrupt poliovirus circulation in Pakistan, and children remain at risk
      unless routine immunization is strengthened or additional supplementary
      immunization is provided.

PMID- 10882576
TI  - Duration of viremia in hepatitis A virus infection.
AB  - The duration of viremia and time course for development of IgM antibodies were
      determined prospectively in natural and experimental hepatitis A virus (HAV)
      infection. Serial serum samples from HAV-infected men (n=13) and experimentally
      infected chimpanzees (n=5) were examined by nested reverse-transcriptase
      polymerase chain reaction analysis to detect HAV RNA and by ELISA to detect IgM
      antibodies to HAV. Among infected humans, HAV RNA was detected an average of 17
      days before the alanine aminotransferase peak, and viremia persisted for an
      average of 79 days after the liver enzyme peak. The average duration of viremia
      was 95 days (range, 36-391 days). Results were similar in chimpanzees. In
      addition, HAV RNA was detected in serum of humans and chimpanzees several days
      before IgM antibodies to HAV were detected. These results indicate that adults
      with HAV infection are viremic for as long as 30 days before the onset of
      symptoms and that the duration of viremia may be longer than previously
      described.

PMID- 10882577
TI  - DNA prime-canarypox boost with polycistronic hepatitis C virus (HCV) genes
      generates potent immune responses to HCV structural and nonstructural proteins.
AB  - DNA vaccination was employed to study immune responses to hepatitis C virus (HCV)
      proteins. As an immunizing strategy, we studied immune responses of BALB/c (H-2d)
      and C57BL/6 mice (H-2b) to HCV genes delivered intramuscularly as a polycistronic
      construct capsid/E1/E2/NS2/NS3 (pRC/C-NS3) encoding 5 structural and
      nonstructural proteins. We also evaluated canarypox virus containing the same HCV
      genes as a means for potentiating immune responses to naked DNA. Our results
      indicate that mice that received a polycistronic pRC/C-NS3 with canarypox booster
      had enhanced antibody and cellular responses to HCV proteins. Immunodominant
      CD8(+) T cell responses to several HCV structural and nonstructural proteins,
      characterized by cytotoxicity and interferon (IFN)-gamma production or IFN-gamma
      production without significant cytotoxicity, were observed in both strains of
      mice. The combination of naked DNA with a nonreplicating canarypox booster
      encoding HCV polycistronic pRC/C-NS3 genes appears to diversify and enhance T
      cell responses to HCV proteins.

PMID- 10882578
TI  - Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus.
AB  - Many studies have shown that patients infected with hepatitis C virus (HCV) of
      genotype 2 have better response to interferon (IFN)-alpha treatment than genotype
      1 patients; however, the mechanisms responsible for this difference are not
      understood. In this study, viral dynamics during high-dose IFN induction
      treatment were compared between the genotypes. Patients in each group received 10
      MU of IFN-alpha2b for 14 days, and HCV RNA levels were frequently determined.
      Nonlinear fitting, both individually for each patient and using a mixed-effects
      approach, of the viral kinetic data to a mathematical model of the IFN effect on
      HCV infection was performed. The antiviral effectiveness of IFN in blocking virus
      production, the free virion clearance rate, and the HCV-infected cell death rate
      were all significantly higher for genotype 2 patients than for genotype 1
      patients. Thus, the better response rate of patients infected with HCV genotype 2
      is multifactorial. This is the first finding of a difference in viral dynamics
      between subtypes of the same virus and demonstrates the importance of subtype
      specific virus-host-drug interactions.

PMID- 10882579
TI  - New molecular assays to predict occurrence of cytomegalovirus disease in renal
      transplant recipients.
AB  - Thirty renal transplant recipients, after transplantation, were tested weekly
      with the following assays: cytomegalovirus (CMV) antigenemia (pp65 Ag), plasma
      qualitative Amplicor CMV (P-AMP), plasma and peripheral blood leukocyte
      quantitative Amplicor CMV monitor (P- and PBL-CMM), peripheral blood leukocyte
      (PBL) quantitative Quantiplex bDNA CMV, version 2.0 (bDNA), and whole-blood
      Nuclisens pp67 CMV (pp67). Eleven patients developed symptomatic CMV disease, and
      7 developed asymptomatic CMV infection. For prediction of CMV disease, the
      sensitivity, specificity, and positive and negative predictive values,
      respectively, were as follows: 100%, 63%, 61%, and 100% for pp65 Ag; 100%, 42%,
      50%, and 100% for bDNA; 91%, 47%, 50%, and 90% for PBL-CMM; 55%, 74%, 55%, and
      74% for P-AMP; 55%, 74%, 55%, and 74% for P-CMM; and 64%, 79%, 64%, and 79% for
      pp67. First positive results in PBL were obtained 9-10 days before symptoms of
      CMV disease, compared with 5-6 days in plasma and 0 days in whole blood. PBL
      assays appear to be more appropriate than plasma assays when pre-emptive therapy
      is required to prevent the rapid progression from the first detection of the
      virus to CMV disease.

PMID- 10882580
TI  - Humoral immune responses in the hantavirus cardiopulmonary syndrome.
AB  - The immunologic responses that mediate viral clearance of and recovery from
      hantavirus cardiopulmonary syndrome (HCPS) due to Sin Nombre (SN) virus are
      unknown. Serial serum samples from 26 patients with acute SN virus infection were
      tested for IgG, IgA, and IgM reactivity to recombinant viral nucleocapsid (N) and
      glycoprotein G1 antigens by a novel strip immunoblot assay. The titers of
      antibodies capable of neutralizing SN virus in vitro also were determined for
      each sample. At admission, patients with severe disease had lower titers of IgG
      antibodies to SN virus N antigen (P<.033) and lower neutralizing antibody titers
      (P<3.4x10-5), compared with patients with mild disease. These data suggest that a
      strong neutralizing antibody response may be a predictor of effective clearance
      of and recovery from SN virus infection and raise the possibility that passive
      immunotherapy may be useful in HCPS.

PMID- 10882581
TI  - Structural prerequisites for intersubtype B and D antigenicity of the third
      variable envelope region (V3) of human immunodeficiency virus type 1.
AB  - To elucidate the structural requirements for intersubtype antigenicity of human
      immunodeficiency virus type 1 (HIV-1) third variable envelope region (V3),
      synthetic peptides were used in enzyme immunoassays (EIAs) with serum samples
      from persons with proven or probable subtype B and D infections. Mathematical
      analyses of results from EIAs with singly substituted V3 peptides revealed
      important residues determining overall N-terminal V3 peptide antigenicity. This
      information was used to design V3 immunogens, rabbit antiserum to which were
      tested in EIA and for in vitro neutralization of molecular clones of HIV-1(MN)
      and HIV-1(MAL). Intersubtype-reactive epitopes were distributed toward the N
      terminal half of the V3 loop. Lysine at position 310, arginine at position 311,
      and isoleucine at position 314, all derived from the MN primary sequence, were
      major determinants of intersubtype V3 antigenicity. Combinations of residues that
      enhanced antigenicity often contained lysine at position 310. Threonine at
      position 308 was common in the least advantageous combinations. V3 immunogens
      modified to achieve optimal antigenicity induced antiserum with augmented cross
      neutralization of virus from MAL and MN molecular clones, suggesting one approach
      to subunit vaccine development.

PMID- 10882582
TI  - Methods for investigation of the relationship between drug-susceptibility
      phenotype and human immunodeficiency virus type 1 genotype with applications to
      AIDS clinical trials group 333.
AB  - Use of human immunodeficiency virus (HIV) drug-resistance testing in therapeutic
      decision making may be aided by understanding the relationship between results of
      genotypic and drug-susceptibility phenotypic assays. We investigated this
      relationship by applying 3 different statistical methods-cluster analysis,
      recursive partitioning, and linear discriminant analysis-to results for 72
      patients followed in the Adult AIDS Clinical Trials Group (ACTG) protocol 333.
      ACTG 333 was a multicenter, randomized trial comparing 2 formulations of
      saquinavir (SQV) to indinavir (IDV) in patients with extensive hard-gel SQV
      experience. Data include protease amino acid sequences and 50% inhibitory
      concentrations for SQV and IDV at baseline. The 3 methods give similar results
      showing the association of mutations at codons 10, 63, 71, and 90 with in vitro
      resistance to IDV and SQV. Recursive partitioning is especially useful because it
      can identify interactions among mutations at different codons and accommodates
      many types of data as well as missing observations.

PMID- 10882583
TI  - Consistent and significant inhibition of human immunodeficiency virus type 1
      envelope-mediated membrane fusion by beta-chemokines (RANTES) in primary human
      macrophages.
AB  - Infection and entry of CD4(+) cells by human immunodeficiency virus type 1 (HIV
      1) requires a coreceptor molecule, which, in concert with CD4, interacts with the
      viral envelope glycoprotein (Env), leading to membrane fusion. The principal
      coreceptors are the CCR5 and CXCR4 chemokine receptors. The suppressive effect of
      beta-chemokines, principally RANTES, on certain HIV-1 isolates was established
      before the discovery of the CCR5 receptor, and there have since been multiple
      reports confirming this initial observation. However, the inhibitory effect of
      beta-chemokines on HIV-1 infection of macrophages has been controversial. The
      current study focused on this issue in detail, with a reductionist approach,
      using assays that measure the effect of beta-chemokines solely on Env-mediated
      fusion. It is shown that under a variety of culture and differentiation
      conditions, RANTES maintains a significant and consistent inhibitory effect on
      CCR5-dependent Env-mediated fusion, and the role of these findings is discussed
      in relation to the role of beta-chemokines in HIV pathogenesis.

PMID- 10882584
TI  - Human immunodeficiency virus type 1 shedding pattern in semen correlates with the
      compartmentalization of viral Quasi species between blood and semen.
AB  - High levels of human immunodeficiency virus (HIV) type 1 have been detected in
      semen at all stages of disease. However, it is not clear whether HIV-1 is shed in
      semen continuously or intermittently. In a prospective longitudinal study, viral
      RNA was measured weekly for 10 weeks in semen and blood of HIV-seropositive
      subjects. Results showed three different patterns of HIV-1 shedding in semen:
      none (28%), continuous (28%), and intermittent (44%). In contrast, there was no
      change in blood plasma virus load during the study period. Phylogenetic analysis
      of the envelope sequences of HIV-1 RNA in semen and blood revealed distinct virus
      populations in semen and blood of intermittent shedders but similar virus
      populations in the semen and blood of continuous shedder. These results indicate
      for the first time that HIV-1 is shed primarily in an intermittent manner and
      that shedding patterns of HIV-1 in semen are related to compartmentalization of
      HIV-1 between semen and blood.

PMID- 10882585
TI  - The impact of early initiation of highly active antiretroviral therapy on the
      human immunodeficiency virus type 1-specific CD8 T cell response in children.
AB  - This cross-sectional study investigated the effect of early highly active
      antiretroviral therapy (HAART) on human immunodeficiency virus (HIV) type 1
      specific CD8 T cell responses in children. HIV-1-specific CD8 T cell responses
      were quantified using an enzyme-linked immunospot assay to measure interferon
      gamma-secreting cells. HIV-1-infected children were classified by time of HAART
      initiation prior to age 1 year or after age 2 years as early (n=24) or late
      (n=28) treated. The magnitude and breadth of the HIV-1-specific CD8 T cell
      response was significantly lower in children receiving early compared with late
      HAART treatment (P=.0007 and.0001, respectively). However, total CD8 T cell
      responses in the early HAART treatment group did not differ significantly from
      those of age-matched non-HAART-treated controls (n=30). Thus, the reduced
      magnitude and breadth of the HIV-1-specific CD8 T cell response in early HAART
      treated children is due to their younger age.

PMID- 10882586
TI  - Immunologic response to combination nucleoside analogue plus protease inhibitor
      therapy in stable antiretroviral therapy-experienced human immunodeficiency virus
      infected children.
AB  - The response of 40 immunologic parameters was studied for 147 clinically stable,
      protease inhibitor-naive, human immunodeficiency virus (HIV)-infected children
      aged 2-17 years when antiretroviral therapy was changed to either a dual
      nucleoside analogue regimen or a protease inhibitor-containing regimen.
      Immunologic response to therapy, as measured by lymphocyte subsets, 3-color flow
      cytometric measures, and lymphoproliferative assays, were investigated for
      changes in weeks 44 and 48. The most significant changes after baseline that were
      associated with the administration of a protease inhibitor-containing regimen
      were seen for percentages of CD8(+)/CD38(+)/HLA-DR(+), CD8(+)/CD95(+)/CD28(-),
      and CD8. The percentages of CD8(+)/CD38(+)/HLA-DR(+) and CD8(+)/CD95(+)/CD28(-)
      decreased from baseline medians of 33% and 46% to medians of 18% and 30% at week
      44 (P<.0001 for both). Median CD4 cell count increased 168 cells/microL (from 694
      cells/microL to 862 cells/microL; P=.02) by week 48 in this clinically stable
      population. Changes in lymphoproliferative responses to HIV antigens and recall
      antigens did not increase over time and between groups.

PMID- 10882587
TI  - Disease progression and early viral dynamics in human immunodeficiency virus
      infected children exposed to zidovudine during prenatal and perinatal periods.
AB  - Zidovudine (Zdv) is widely used to reduce maternal-infant human immunodeficiency
      virus transmission (HIV), but its consequences for disease progression among
      children infected despite Zdv exposure remain unknown. In a multicenter
      observational cohort study of 325 HIV-infected children born during 1986-1997,
      clinical progression was compared among infected children exposed or unexposed to
      Zdv during prenatal and perinatal periods. Zdv exposure was associated with 1.8
      fold (95% confidence interval, 1.02-3.11) increased risk of progressing to AIDS
      or death after adjusting for year of birth, maternal CD4 cell count, maternal
      AIDS diagnosis, and subsequent antiretroviral therapy of the child. Mean log(10)
      viral copies at 7-12 weeks were higher among Zdv-exposed children (P=.004). No
      infected child treated early with multidrug therapy progressed to AIDS or died by
      1 year, regardless of early Zdv exposure. More rapid disease progression was
      observed among infected children exposed during pregnancy or birth to Zdv if
      effective multidrug therapy was not initiated.

PMID- 10882588
TI  - Selection of drug-resistant variants in the female genital tract of human
      immunodeficiency virus type 1-infected women receiving antiretroviral therapy.
AB  - We investigated human immunodeficiency virus (HIV) type 1 RNA, proviral DNA, and
      antiretroviral drug-resistant variants in cervicovaginal secretions of HIV-1
      infected women receiving antiretroviral therapy. The prevalence of detectable HIV
      1 RNA in genital secretions was inversely related to the number of antiretroviral
      drugs taken by the patients. Proviral DNA was detected in approximately half of
      all samples of cervicovaginal secretions from HIV-1-infected women, regardless of
      the presence or absence of HIV-1 RNA in cervicovaginal secretions and of the
      antiretroviral regimen. In cervicovaginal secretions of most women with
      persisting genital viral replication, HIV variants exhibiting mutations
      associated with drug resistance against protease and reverse-transcriptase pol
      genes were found. Our observations indicate that antiretroviral therapy is not
      effective in purging the female genital tract of cell-associated provirus and
      that antiretroviral drugs that penetrate the female genital tract at suboptimal
      concentrations exert a potent selective pressure on genital HIV variants when
      local replication of free HIV-1 RNA persists.

PMID- 10882589
TI  - Factors contributing to the lack of human immunodeficiency virus type 1 (HIV-1)
      transmission in HIV-1-discordant partners.
AB  - Correlates of resistance to infection by human immunodeficiency virus type 1 (HIV
      1) are important for defining potential therapeutic interventions and for
      prophylactic vaccination. In this study, 11 couples discordant in their HIV-1
      infection status were prospectively evaluated for the presence of protective
      factors. Behavioral characteristics of all subjects entailed a high risk of
      transmission. Cytotoxic T lymphocyte (CTL) responses against viruses isolated
      from the infected partner, and against laboratory virus isolates, were detected
      in 5 (45%) of 11 HIV-negative partners, including a CCR5Delta32-homozygous and a
      heterozygous subject. No CTL responses were observed in 6 control unexposed
      subjects. Marked variation in lymphocyte susceptibility to viral infection was
      noted. Resistance attributable to major histocompatibility complex discordance or
      anti-major histocompatibility complex antibodies was not identified. These
      results suggest that a combination of factors, including cellular immunity, viral
      characteristics, and coreceptor integrity, may be involved in the persistent
      nontransmission of HIV.

PMID- 10882590
TI  - Acute serogroup A streptococcal shock: A porcine model.
AB  - To elucidate the pathophysiology of acute shock caused by serogroup A
      streptococci (GAS), GAS were given intravenously to 25 pigs. Short-time infusions
      of GAS (n=11) caused variable and unpredictable responses. A continuous infusion
      of 5x108 cfu/kg/h (n=8) caused pulmonary hypertension, arterial hypotension, and
      reduced cardiac output and liver perfusion, progressing to circulatory shock
      within 2-4 h. Halving the infusion rate (n=6) induced a more gradual development
      of shock and doubled the mean survival time from 2.1 to 4.0 h. Mean tumor
      necrosis factor-alpha levels (+/-SE) increased from 25+/-1 to 40+/-3 pg/mL. Only
      slight signs of organ dysfunction were observed, which indicates that this is
      primarily a model of acute septic shock. Light microscopy revealed moderate
      inflammatory reactions in lung, liver, and gut biopsy samples, although high
      numbers of viable, M-typeable GAS were recovered from tissues. The present model
      may be useful to study mechanisms involved in acute septic shock as well as
      therapeutic interventions.

PMID- 10882591
TI  - Cross-protection between group A and group B streptococci due to cross-reacting
      surface proteins.
AB  - The R28 protein of group A streptococcus (GAS) and the Rib protein of group B
      streptococcus (GBS) are surface molecules that elicit protective immunity to
      experimental infection. These proteins are members of the same family and cross
      react immunologically. In spite of extensive amino acid residue identity, the
      cross-reactivity between R28 and Rib was found to be limited, as shown by
      analysis with highly purified proteins and specific antisera. Nevertheless,
      immunization of mice with purified R28 conferred protection against lethal
      infection with Rib-expressing GBS strains, and immunization with Rib conferred
      protection against R28-expressing GAS. Thus, R28 and Rib elicited cross
      protective immunity. Characterization of many clinical GAS and GBS isolates
      expressing R28 or Rib, respectively, indicated that most of them expressed
      proteins similar to those of the reference strains. Analysis of these data
      suggests that cross-protection may influence the outcome of natural infections
      with R28-expressing GAS and Rib-expressing GBS.

PMID- 10882592
TI  - Group B streptococcal beta-hemolysin induces nitric oxide production in murine
      macrophages.
AB  - Group B streptococcus (GBS) is the leading cause of sepsis in neonates. Nitric
      oxide (NO) release plays a role in the hypotension that characterizes septic
      shock. To examine the role of the GBS beta-hemolysin in NO production, the murine
      macrophage line RAW 264. 7 was exposed to a wild-type (WT) GBS isolate and to
      hyperhemolytic (HH) and nonhemolytic (NH) transposon mutants derived from that
      isolate. After activation of macrophages by the WT strain, the HH mutant, or cell
      free extracts of beta-hemolysin, nitrite release into the supernatant increased
      >10-fold and inducible NO synthase (iNOS) levels in cell lysates increased up to
      10-fold compared with treatment with the NH mutant or extracts from that mutant.
      Hemolysin-induced NO production was dependent on protein tyrosine kinases and NF
      kappaB, but not on extracellular signal-related kinase-1/2-mitogen-activated
      kinases or protein kinase A. These results indicate that GBS beta-hemolysin
      induces murine macrophage iNOS via intracellular pathways similar to those that
      mediate lipopolysaccharide-induced iNOS activation.

PMID- 10882593
TI  - Antibody to capsular polysaccharide of Streptococcus pneumoniae at the time of
      hospital admission for Pneumococcal pneumonia.
AB  - IgG to capsular polysaccharide (CPS) of Streptococcus pneumoniae is thought to
      provide the greatest degree of protection against pneumococcal disease. Serum
      obtained at hospital admission from 14 (27%) of 51 patients with bacteremic
      pneumococcal pneumonia and 11 (37%) of 30 with nonbacteremic pneumococcal
      pneumonia contained IgG to CPS of the infecting serotype; these percentages are
      similar to the prevalence of IgG to CPS in a control population. However, when
      compared with antibody from healthy adults, this IgG had far less capacity to
      opsonize the infecting pneumococcal serotype for phagocytosis in vitro by normal
      human polymorphonuclear leukocytes or to protect mice against experimental
      challenge. Failure to opsonize correlated closely with failure to protect mice,
      and each of these parameters correlated well with poor avidity for CPS. Future
      vaccine studies may need to examine the functional capacity of antibodies as a
      surrogate for infection, in addition to measuring their concentration in serum.

PMID- 10882594
TI  - Invasive disease due to group B streptococcal infection in adults: results from a
      Canadian, population-based, active laboratory surveillance study--1996. Sentinel
      Health Unit Surveillance System Site Coordinators.
AB  - In 1996, a population-based surveillance program for invasive adult group B
      streptococcal (GBS) diseases in Canada was undertaken, to define the
      epidemiologic and microbiologic characteristics of the disease. Nine public
      health units across Canada, representing 9.6% of the population, participated in
      the program. In total, 106 culture-positive cases of invasive adult GBS disease
      were reported, which represented an incidence rate 4.6 per 100,000 adults
      (41/100, 000 for pregnant and 4.1/100,000 for nonpregnant adults). Sixty-two
      (58.5%) of the 106 cases occurred in females, and, of these, 15 (14. 2%) were
      associated with pregnancy. Serotype V was the most common, accounting for 31% of
      the 90 GBS isolates typed (26.7% of nonpregnant and 4.4% of pregnant cases). This
      was followed by serotypes III (19%), Ia (17%), Ib (10%), II (9%), and VII (1%).
      Thirteen percent were nontypeable. All isolates were susceptible to penicillin,
      ampicillin, and vancomycin. Resistance to erythromycin and clindamycin was 6.7%
      and 4.4%, respectively.

PMID- 10882595
TI  - Morbidity of pertussis in adolescents and adults.
AB  - The effect of age on the clinical presentation of pertussis was assessed in 664
      adolescent and adult cases. Complications were more frequent in adults than in
      adolescents (28% vs. 16%). Pneumonia occurred in 2% of patients <30 years old but
      in 5%-9% of older patients. Urinary incontinence occurred in 34% of women >/=50
      years old. Duration of cough, risk of sinusitis, and number of nights with
      disturbed sleep increased with smoking and asthma. The secondary attack rate in
      other household members >/=12 years was 11%. Pertussis in secondary case patients
      was less severe than in index case patients but presented with classic symptoms.
      The main source of infection in adolescents was schoolmates or friends; in adults
      it was workplace or their children. Teachers and health care workers had a
      greater risk of pertussis than did the general population. The burden of disease
      appears to increase with age, with smoking, and with asthma.

PMID- 10882596
TI  - Enterotoxin adjuvants have direct effects on T cells and antigen-presenting cells
      that result in either interleukin-4-dependent or -independent immune responses.
AB  - In an in vitro study, Escherichia coli heat-labile toxin (LT) was shown to
      directly affect activated CD4(+) T cells and support interleukin (IL)-5
      production in IL-4-deficient (IL-4(-/-)) mice, whereas cholera toxin (CT) did
      not. Both LT and CT enhanced B7-2 expression on B cells and macrophages. These
      effects were not influenced by CD40-CD40 ligand cosignaling. Addition of LT- or
      CT-treated antigen-presenting cells to anti-CD3-triggered CD4(+) T cells resulted
      in the induction of T cell proliferative responses. Further, these responses were
      inhibited by anti-B7-2 monoclonal antibody. Cocultivation of CD4(+) T cells with
      LT- or CT-treated antigen-presenting cells and anti-CD3 enhanced Th1- and IL-4
      mediated Th2-type cytokine production. The results from in vitro studies were
      supported by in vivo studies in IL-4(-/-) mice, in which LT induced mucosal IgA
      responses but CT did not. Thus, although both LT and CT induce mucosal adjuvant
      responses via IL-4-dependent Th2-type responses, LT also elicits Th1- and IL-4
      independent Th2-type responses.

PMID- 10882597
TI  - Targeting lipopolysaccharides by the nontoxic polymyxin B nonapeptide sensitizes
      resistant Escherichia coli to the bactericidal effect of human neutrophils.
AB  - The nonapeptide of polymyxin B (PMBN) has been reported to sensitize various
      pathogenic gram-negative bacteria to the direct bactericidal effect of human
      serum. To investigate the impact of PMBN on human neutrophil-effected killing of
      the serum- and phagocytosis-resistant Escherichia coli strains C14 and O111,
      serum was coapplied with PMBN or with neutrophils, but this did not result in
      decreased numbers of viable bacteria. In contrast, the most potent bacterial
      killing occurred in the presence of neutrophils plus serum components plus PMBN.
      The effect of this on E. coli C14 was the appearance of inositol phosphates,
      diacylglycerol, respiratory burst, elastase liberation, and generation of lipid
      mediators (leukotriene B(4), 5-HETE, and platelet-activating factor). Strong
      neutrophil activation required early, but not late, complement components and was
      blocked by inhibition of phagocytosis with cytochalasin D. PMBN seems to cause
      dramatic support of natural host defense by complement-dependent sensitization of
      E. coli to the bactericidal efficacy of human neutrophils.

PMID- 10882598
TI  - The agent of human granulocytic ehrlichiosis induces the production of
      myelosuppressing chemokines without induction of proinflammatory cytokines.
AB  - Infection by human granulocytic ehrlichiosis (HGE) is characterized clinically by
      cytopenias out of proportion to the number of cells seen to be infected directly.
      To study the pathogenic role of inflammatory mediators in HGE infection, cytokine
      production by untreated and dimethyl sulfoxide-treated HL-60 cells, which
      demonstrate enhanced infection because of granulocytic differentiation, and by
      normal bone marrow cells was measured using modified sandwich ELISA assays on
      samples obtained sequentially after inoculation with the HGE agent. All infected
      cells produced physiological concentrations of CC (monocyte chemotactic protein
      1, macrophage inflammatory protein-1alpha and -beta, and RANTES) and CXC
      (interleukin [IL]-8) chemokines in amounts significantly greater than those
      produced by uninfected controls. In contrast, infected cells did not secrete the
      classic proinflammatory cytokines IL-1, IL-6, or tumor necrosis factor-alpha. The
      striking production of chemokines, powerful leukocyte chemoattractants capable of
      suppressing hematopoiesis, by susceptible target cells, is likely to be of
      pathogenic importance both in the observed cytopenias and in mediation of
      inflammation and host defenses during infection.

PMID- 10882599
TI  - Soluble granzymes are released during human endotoxemia and in patients with
      severe infection due to gram-negative bacteria.
AB  - Extracellular release of granzymes is considered to reflect the involvement of
      cytotoxic T lymphocytes and NK cells in various disease states. To obtain insight
      into granzyme release during bacterial infection, granzyme levels were measured
      during experimental human endotoxemia and in patients with melioidosis, a severe
      infection due to gram-negative bacteria. Plasma concentrations of granzyme A
      (GrA) and GrB increased transiently after endotoxin administration, peaking after
      2-6 h. In patients with bacteremic melioidosis, GrA and GrB levels were elevated
      on admission and remained high during the 72-h study period. In whole blood
      stimulated with heat-killed Burkholderia pseudomallei, neutralization of tumor
      necrosis factor, interleukin-12, or interleukin-18 inhibited granzyme secretion,
      which was independent of interferon-gamma. Stimulation with endotoxin and other
      gram-negative and gram-positive bacteria also strongly induced the secretion of
      granzymes, suggesting that granzyme release is a general immune response during
      bacterial infection. The interaction between the cytokine network and granzymes
      may play an important immunoregulatory role during bacterial infections.

PMID- 10882600
TI  - Role of nitric oxide in the failure of neutrophil migration in sepsis.
AB  - The cecal ligation and puncture (CLP) model was used to investigate whether
      failure of neutrophil migration occurs in sepsis and whether it correlates with
      disease outcome. It was observed that the severity of sepsis correlates with the
      number of punctures in the cecum: mice with 2 punctures (sublethal [SL]-CLP)
      developed mild peritonitis (100% survived), whereas mice with 12 punctures
      (lethal [L]-CLP) developed severe peritonitis and bacteremia that evolved to
      sepsis (none survived). The production of tumor necrosis factor-alpha,
      interleukin-1beta, and interleukin-10 was higher in L-CLP than in SL-CLP mice.
      The impairment of neutrophil migration to the peritoneum and to the cecum wall
      was observed only in L-CLP mice. This phenomenon was shown to be mediated by
      nitric oxide, because aminoguanidine prevented the failure of neutrophil
      migration and improved the survival of L-CLP animals. In conclusion, impairment
      of neutrophil migration is a crucial event in the worsening of sepsis, and nitric
      oxide seems to be responsible for the phenomenon.

PMID- 10882601
TI  - Cloning of a Mycobacterium tuberculosis gene encoding a purifed protein
      derivative protein that elicits strong tuberculosis-specific delayed-type
      hypersensitivity.
AB  - The purified protein derivative (PPD) skin test has been used for the diagnosis
      of tuberculosis for more than 75 years. However, the test lacks specificity
      because all mycobacteria share antigens present in PPD. Therefore, sensitization
      with nontuberculous pathogenic or with environmental nonpathogenic mycobacteria
      can lead to positive skin tests. This communication describes a novel PPD protein
      present only in tuberculous complex mycobacteria. A recombinant protein was
      obtained and named DPPD on the basis of the first 4 amino acids of its N-terminus
      sequence. DPPD elicited delayed-type hypersensitivity (DTH) in 100% of
      Mycobacterium tuberculosis-infected guinea pigs but in no animals sensitized with
      several organisms representative of all members of the Mycobacterium genus.
      Preliminary results indicate that DPPD induces strong and specific DTH in humans.
      This work points to the definition of a single recombinant M. tuberculosis
      protein that may be an alternative to the PPD test.

PMID- 10882602
TI  - Production of interleukin-18 in human tuberculosis.
AB  - To investigate the role of interleukin (IL)-18 in human tuberculosis, IL-18
      production was evaluated in blood and at the site of disease in patients with
      tuberculosis. Mycobacterium tuberculosis-stimulated peripheral blood mononuclear
      cells (PBMC) from tuberculosis patients secreted less IL-18 and interferon-gamma
      (IFN-gamma) than did PBMC from healthy persons reactive to tuberculin. M.
      tuberculosis-induced IFN-gamma production was inhibited by anti-IL-18 and
      enhanced by recombinant IL-18. Alveolar macrophages secreted IL-18 in response to
      M. tuberculosis, and IL-18 and IFN-gamma concentrations were higher in pleural
      fluid of patients with tuberculosis than in pleural fluid of patients with
      nontuberculous diseases. These findings demonstrate that IL-18 production by PBMC
      correlates with IFN-gamma production and effective immunity to tuberculosis,
      suggesting that IL-18 contributes to a protective type 1 cytokine response in
      persons with mycobacterial infection.

PMID- 10882603
TI  - Mannosylated lipoarabinomannan antagonizes Mycobacterium tuberculosis-induced
      macrophage apoptosis by altering Ca+2-dependent cell signaling.
AB  - Mycobacterium tuberculosis-induced macrophage apoptosis can be inhibited by
      mannosylated lipoarabinomannan (ManLAM), although it induces tumor necrosis
      factor (TNF)-alpha and NO production, which participate in apoptosis induction.
      ManLAM also modulates Ca(+2)-dependent intracellular events, and Ca(+2)
      participates in apoptosis in different systems. Ca(+2) was assessed for
      involvement in M. tuberculosis-induced macrophage apoptosis and for modulation by
      ManLAM. The role of Ca(+2) was supported by the blockade of apoptosis by cAMP
      inhibitors and the Ca(+2) chelator, BAPTA/AM. These agents also inhibited caspase
      1 activation and cAMP-responsive element-binding protein translocation without
      affecting TNF-alpha production. Infection of macrophages with M. tuberculosis
      induced an influx of Ca(+2) that was prevented by ManLAM. Similarly, M.
      tuberculosis infection-altered mitochondrial permeability transition was
      prevented by ManLAM and BAPTA/AM. Finally, ManLAM and BAPTA/AM reversed the
      effects of M. tuberculosis on p53 and Bcl-2 expression. ManLAM counteracts the
      alterations of calcium-dependent intracellular events that occur during M.
      tuberculosis-induced macrophage apoptosis.

PMID- 10882604
TI  - Plasmodium falciparum-infected erythrocytes: agglutination by diverse Kenyan
      plasma is associated with severe disease and young host age.
AB  - The variant surface antigens (VSAs) of Plasmodium falciparum-infected red blood
      cells are potentially important targets of naturally acquired immunity to
      malaria. Natural infections induce agglutinating antibodies specific to the VSA
      variants expressed by the infecting parasites. Previously, when different
      parasite isolates were tested against a panel of heterologous plasma from Kenyan
      children, the proportion of plasma that agglutinated the parasites (the
      agglutination frequency [AF]) was highly variable among isolates, suggesting the
      existence of rare and prevalent variants. Here, the AF of 115 isolates from
      Kenyan children were compared. The results show that the AF of isolates causing
      severe malaria were significantly higher than those of isolates causing mild
      malaria; and AF decreased significantly with the increasing age of the infected
      child. We propose that parasites causing severe disease tend to express a subset
      of VSA variants that are preferentially associated with infections of children
      with low immunity.

PMID- 10882605
TI  - Chronic schistosomiasis: dendritic cells generated from patients can overcome
      antigen-specific T cell hyporesponsiveness.
AB  - Chronic infection with helminths is associated with down-regulated antigen
      specific T cell responses. In order to determine whether schistosome-specific T
      cells are present, yet functionally unresponsive, or absent in the periphery of
      chronically infected persons, autologous granulocyte-macrophage colony
      stimulating factor and dendritic cells (DC) derived from interleukin (IL)-4 were
      used as highly efficient antigen-presenting cells (APC). Peripheral blood
      mononuclear cells (PBMC) from persons harboring Schistosoma haematobium infection
      and hyporesponsive to parasite antigen were cocultured with autologous DC in the
      presence of adult worm antigen (AWA). In contrast to PBMC alone, DC-supplemented
      cultures responded to AWA by proliferation and by IL-4 and IL-5 production and,
      in some patients, by production of interferon-gamma. Thus, schistosome-specific T
      helper cells are present in the periphery but are functionally hyporesponsive
      during active infection with schistosomes. Cytokine responses representing the
      Th1 and (more importantly) Th2 types can be restored in vitro when DC are used as
      APC.

PMID- 10882606
TI  - Increased resistance to systemic candidiasis in athymic or interleukin-10
      depleted mice.
AB  - Candida albicans produces a virulence-associated immunomodulatory protein (p43),
      which activates lymphocytes polyclonally, suppresses specific antibody responses
      to Candida antigens, and potentiates systemic growth of C. albicans. In this
      study, athymic, unlike euthymic, C57BL/6 mice were resistant to systemic
      candidiasis and produced lower serum levels of interleukin (IL)-4 and IL-10.
      Pretreatment with p43 stimulated the production of both cytokines. Depletion of
      IL-10, but not of IL-4, in euthymic animals reestablished resistance and
      abrogated p43-dependent suppression of the specific antibody response and
      facilitated C. albicans growth. In agreement with these results, both
      immunosuppression and p43-mediated facilitation of the fungus growth were
      abolished in IL-10 knockout mice. These observations demonstrate the relevance of
      IL-10 in facilitating systemic candidiasis and suggest a critical role for the
      immunosuppressive virulence factor p43 in the process.

PMID- 10882607
TI  - Comparative efficacy and distribution of lipid formulations of amphotericin B in
      experimental Candida albicans infection of the central nervous system.
AB  - The central nervous system (CNS) distribution and antifungal efficacy of all 4
      approved formulations of amphotericin B (AmB) were investigated in a rabbit model
      of hematogenous Candida albicans meningoencephalitis. Treatment with AmB
      deoxycholate (1 mg/kg/day) or liposomal AmB (5 mg/kg/day) yielded the highest
      peak plasma concentration (C(max)), area under concentration versus time curve
      from zero to 24 h (AUC(0-24)), and time during dosing level tau Ttau>minimum
      inhibitory complex (MIC) values and led to complete eradication of C. albicans
      from brain tissue (P<.05 vs. untreated controls). By comparison, AmB colloidal
      dispersion and AmB lipid complex (5 mg/kg/day each) were only partially effective
      (not significant vs. untreated controls). There was a strong correlation of
      C(max), AUC(0-24), C(max)/MIC, AUC(0-24)/MIC, and Ttau>MIC with clearance of C.
      albicans from brain tissue (P</=.0002). Although pharmacodynamic parameters
      derived from the MIC of free AmB were highly predictive of antifungal efficacy,
      parameters derived from MICs of individual formulations were not predictive. AmB
      deoxycholate and liposomal AmB had the greatest antifungal efficacy. This
      activity was concentration and time dependent.

PMID- 10882608
TI  - Conditional lethality of the diprotic weak bases chloroquine and quinacrine
      against Cryptococcus neoformans.
AB  - Chloroquine at 10 microM enhances the activity of macrophages against
      Cryptococcus neoformans but does not directly inhibit cryptococcal growth. The
      antifungal activity of higher chloroquine concentrations likely to be found
      within the acidic cryptococcal phagosome was tested. Concentrations of >/=30
      microM inhibited cryptococcal growth, and there was fungal killing at
      concentrations of >/=100 microM. Activity was dependent on physiologic
      temperature and pH. Quinacrine was 50-fold more active than chloroquine, and
      concentrations as low as 100 nM enhanced macrophage anticryptococcal activity.
      Quinacrine was concentrated within a vacuolar system within the fungal cell and
      highly concentrated within intracellular C. neoformans. Ammonium chloride and
      bafilomycin A both inhibited cryptococcal growth, suggesting that the activity of
      chloroquine and quinacrine may in part be due to disruption of pH-dependent
      processes. These findings add to the known spectrum of activity of chloroquine
      and quinacrine. These, and related compounds, may have utility for the treatment
      of cryptococcosis.

PMID- 10882610
TI  - Identification of 2 novel isolates of hepatitis E virus in Argentina.
AB  - Hepatitis E virus (HEV) has been identified in 2 Argentine patients with acute
      hepatitis who reported no history of travel to regions in which HEV is considered
      endemic. These isolates are the first to be identified in South America. By use
      of degenerate primers from open reading frames 1 and 2, HEV sequences were
      obtained from these patients' serum and compared with published HEV sequences.
      The Argentine isolates are different from all previously identified HEV isolates
      and are most closely related to each other. The Argentine isolates are distinct
      from the most geographically related isolate from Mexico as well as isolates from
      other endemic (China, Southeast Asia, and India) and nonendemic (the United
      States and Europe) regions. Phylogenetic analysis indicate that the Argentine
      isolates represent a new genotype of HEV, genotype 8, distinct from the Burmese
      like genotype 1, Mexican genotype 2, US genotype 3, Chinese/Taiwan genotype 4,
      and European genotypes 5-7.

PMID- 10882609
TI  - Genetic characterization of thymidine kinase from acyclovir-resistant and 
      susceptible herpes simplex virus type 1 isolated from bone marrow transplant
      recipients.
AB  - Emergence of acyclovir (Acy)-resistant herpes simplex virus (HSV) is a major
      concern in bone marrow transplant recipients. Phenotypic and genetic
      characterization of thymidine kinase (TK) was done for 7 Acy-susceptible and 11
      Acy-resistant HSV-1 isolated from 11 patients. In total, 19 amino acid
      substitutions were detected that were not related to Acy resistance but to TK
      gene polymorphism, including 5 mutations that have not been previously reported.
      The Acy-resistant strain from 1 patient presented no TK gene mutation related to
      resistance. Five patients (45%) had isolates that harbored point mutations
      leading to amino acid substitutions that could be associated with Acy resistance.
      Of the 5 substitutions detected, 3 have not been previously reported (codons 51,
      83, and 175). A nucleotide insertion or deletion was detected in resistant
      isolates from 5 patients (45%); these mutations are located in homopolymer
      repeats at codon 92 (1 subject) and at codon 146 (4 subjects).

PMID- 10882611
TI  - Stable enterovirus 5' nontranslated region over a 7-year period in a patient with
      agammaglobulinemia and chronic infection.
AB  - Cerebrospinal fluid samples obtained 7 years apart from a patient with chronic
      meningoencephalitis and underlying agammaglobulinemia were examined to determine
      enteroviral genotypic variability. From each sample, amplicons spanning 496
      nucleotides within the 5' nontranslated region were generated directly from the
      cerebrospinal fluid and analyzed. A consensus sequence derived from 3 clones of
      each amplicon revealed only 7 nucleotide changes over the 7-year period within
      the region studied. The observed 5' nontranslated region mutation rate in this
      patient ( approximately 0.2% per year) was significantly lower than mutation
      rates reported for the poliovirus genome.

PMID- 10882612
TI  - Human immune responses to a novel norwalk virus vaccine delivered in transgenic
      potatoes.
AB  - A new approach for delivering vaccine antigens is the use of inexpensive,
      plentiful, plant-based oral vaccines. Norwalk virus capsid protein (NVCP),
      assembled into virus-like particles, was used as a test antigen, to determine
      whether immune responses could be generated in volunteers who ingested transgenic
      potatoes. Twenty-four healthy adult volunteers received 2 or 3 doses of
      transgenic potato (n=20) or 3 doses of wild-type potato (n=4). Each dose
      consisted of 150 g of raw, peeled, diced potato that contained 215-751 microgram
      of NVCP. Nineteen (95%) of 20 volunteers who ingested transgenic potatoes
      developed significant increases in the numbers of specific IgA antibody-secreting
      cells. Four (20%) of 20 volunteers developed specific serum IgG, and 6 (30%) of
      20 volunteers developed specific stool IgA. Overall, 19 of 20 volunteers
      developed an immune response of some kind, although the level of serum antibody
      increases was modest.

PMID- 10882613
TI  - Evaluation of the latency-associated nuclear antigen (ORF73) of Kaposi's sarcoma
      associated herpesvirus by peptide mapping and bacterially expressed recombinant
      western blot assay.
AB  - Kaposi's sarcoma (KS)-associated herpesvirus open-reading frame (ORF) 73 encodes
      a latency-associated nuclear antigen (LANA) that is the basis for several
      serologic assays. Immunoreactive epitopes were searched for by peptide mapping,
      and 171 cleavable, biotinylated 17-mer peptides offset by 5 residues were
      synthesized and screened with human serum samples by ELISA. The initial screen,
      which used highly reactive serum diluted 1:500, identified 38 immunoreactive
      peptides. These were subsequently tested on additional serum samples diluted
      1:40. Thirteen peptides were more reactive with serum samples from patients with
      KS than with control serum samples. No single epitope was recognized by most KS
      patient serum samples. Combined use of these peptides did not increase test
      sensitivity to that of current indirect immunofluorescence assays for LANA (80%
      90%). For comparison, full-length ORF73 was expressed in bacteria and analyzed by
      Western blot. The overall sensitivity was 67% (range, 100% among US patients with
      classic KS to 52% among Italian patients with classic KS). These studies suggest
      that LANA immunoreactivity may be due to variations in patient response or
      conformational epitopes.

PMID- 10882614
TI  - Shorter survival of SDF1-3'A/3'A homozygotes linked to CD4+ T cell decrease in
      advanced human immunodeficiency virus type 1 infection.
AB  - The SDF-1 3'A allelic polymorphism has been reported to influence either
      positively or negatively the progression of human immunodeficiency virus type 1
      (HIV-1) disease. Therefore, the SDF-1 genotype of 729 HIV-1-infected individuals
      pooled from 3 distinct cohorts was determined. A statistically nonsignificant
      association between the SDF1-3'A/3'A genotype and accelerated disease progression
      was evident among seroconverters (n=319), but a striking correlation of decreased
      survival after either diagnosis of AIDS according to the 1993 definition or loss
      of CD4(+) T cell counts <200 was observed. The relative hazards for SDF1-3'A/3'A
      homozygotes, compared with heterozygotes and wild-type homozygotes were 2.16
      (P=.0047), for time from diagnosis according to the 1993 Centers for Disease
      Control and Prevention AIDS case definition (AIDS-'93) to death, and 3.43
      (P=.0001), for time from CD4(+) T cells <200 to death. Because no difference in
      survival was observed after diagnosis according to AIDS-'87, the association of
      the SDF1-3'A/3'A genotype with the accelerated progression of late-stage HIV-1
      disease appears to be explained for the most part by the loss of CD4(+) T
      lymphocytes.

PMID- 10882615
TI  - Analysis of env sequence evolution in human immunodeficiency virus-infected
      patients receiving therapy with nonnucleoside reverse-transcriptase inhibitors.
AB  - Nonnucleoside reverse-transcriptase inhibitors (NNRTIs) can rapidly select for
      drug-resistant human immunodeficiency virus type 1 (HIV-1) variants, although
      their effect on HIV-1 quasi-species diversity is unknown. To determine if changes
      in env gene diversification occur with NNRTI therapy, we used the heteroduplex
      tracking assay (HTA) to study HIV-1 env sequence diversity in 2 groups of
      patients: those who were on no therapy or were on chronic antiretroviral therapy
      and those who had just initiated NNRTIs. Forty-nine paired samples from 46
      patients were analyzed. Fourteen of 32 paired samples from the NNRTI group and 9
      of 17 paired samples from the control group had HTA changes (P>.10). There was no
      correlation between HTA change and sampling time interval, baseline virus load,
      change in virus load, or development of NNRTI resistance. Thus, we found no
      significant correlation of NNRTI therapy with changes in env HTA patterns,
      suggesting that these treatments had little short-term impact on HIV-1 quasi
      species diversity.

PMID- 10882616
TI  - In vivo antagonism with zidovudine plus stavudine combination therapy.
AB  - Human immunodeficiency virus (HIV)-infected subjects receiving zidovudine were
      randomized either to add stavudine (d4T) or didanosine (ddI) to their current
      regimen or to switch to ddI or d4T monotherapy. After 16 weeks of therapy, the
      mean reduction in HIV RNA from baseline was 0.14 log(10) copies/mL in patients
      receiving d4T or zidovudine plus d4T. In subjects receiving ddI or ddI plus
      zidovudine, reductions were 0.39 and 0.56 log(10), respectively. CD4 cell counts
      remained stable or showed modest increases in all arms except the zidovudine plus
      d4T arm. Patients receiving zidovudine plus d4T showed progressive declines in
      CD4 cell counts with a median of 22 cells/mm(3) below baseline by 16 weeks.
      Examination of intracellular levels of d4T-triphosphate in 6 subjects was
      consistent with previous in vitro studies demonstrating pharmacologic antagonism
      between zidovudine and d4T. Analysis of these data suggests that zidovudine and
      d4T should not be prescribed in combination and that ddI provides greater
      antiviral activity than d4T in zidovudine-treated patients.

PMID- 10882617
TI  - Single-dose safety, pharmacology, and antiviral activity of the human
      immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected
      adults.
AB  - PRO 542 (CD4-IgG2) is a recombinant antibody-like fusion protein wherein the Fv
      portions of both the heavy and light chains of human IgG2 have been replaced with
      the D1D2 domains of human CD4. Unlike monovalent and divalent CD4-based proteins,
      tetravalent PRO 542 potently neutralizes diverse primary human immunodeficiency
      virus (HIV) type 1 isolates. In this phase 1 study, the first evaluation of this
      compound in humans, HIV-infected adults were treated with a single intravenous
      infusion of PRO 542 at doses of 0.2-10 mg/kg. PRO 542 was well tolerated, and no
      dose-limiting toxicities were identified. Area under the concentration-time
      curve, and peak serum concentrations increased linearly with dose, and a terminal
      serum half-life of 3-4 days was observed. No patient developed antibodies to PRO
      542. Preliminary evidence of antiviral activity was observed as reductions in
      both plasma HIV RNA and plasma viremia. Sustained antiviral effects may be
      achieved with repeat dosing with PRO 542.

PMID- 10882618
TI  - Prevalence of mutations associated with reduced antiretroviral drug
      susceptibility among human immunodeficiency virus type 1 seroconverters in the
      United States, 1993-1998.
AB  - To assess the prevalence of mutations associated with decreased antiretroviral
      drug susceptibility, specimens were tested from persons infected with human
      immunodeficiency virus (HIV) during 1993-1998. Subjects were drug naive and were
      attending sexually transmitted disease clinics in 6 US cities. All were enrolled
      consecutively and had tested negative for HIV during the 2 years before
      enrollment. Plasma specimens from patients having >/=1 reverse transcriptase (RT)
      or primary protease mutation were tested phenotypically with a recombinant virus
      assay. Of 99 patients, 6 (6%) had mutations associated with zidovudine
      resistance, 2 (2%) had mutations associated with nonnucleoside RT inhibitor
      resistance, and 1 (1%) had a primary protease mutation. Overall, the prevalence
      of resistance-associated primary mutations was 5%, although high levels of
      decreased drug susceptibility (IC(50)s >/=10 times that of a reference virus)
      were observed in just 1%. These findings confirm the transmission of these
      mutations to drug-naive persons.

PMID- 10882619
TI  - Incubation time of acute human immunodeficiency virus (HIV) infection and
      duration of acute HIV infection are independent prognostic factors of progression
      to AIDS.
AB  - The severity and the duration of acute human immunodeficiency virus (HIV)
      infection (AHI) are associated with a faster rate of progression to AIDS, but the
      prognostic value of the length of incubation time of AHI (IncAHI), defined as the
      time between HIV infection and AHI, on progression to AIDS has not been assessed.
      We explored this issue prospectively in 70 individuals with documented AHI and a
      known date of HIV infection. The median IncAHI was 21.5 days (range, 5-70 days),
      and the median duration of AHI was 15.5 days (range, 3-67 days). The adjusted
      relative hazard of progression to AIDS or to a CD4(+) count <200x103/mL was 4.23
      (95% confidence interval [CI], 1.40-12.73; P=.01) for the patients with an IncAHI
      <21.5 days, compared with those with longer IncAHI, and was 3.53 (95% CI, 1.09
      11.36; P=.03) for the patients with a duration of AHI >15.5 days, compared with
      those with shorter duration. Both IncAHI and duration of AHI were independent
      predictors of progression. This suggests that early pathogenic events before the
      onset of AHI influence the rate of HIV disease progression.

PMID- 10882620
TI  - In vivo cytolysis and fusion of human immunodeficiency virus type 1-infected
      lymphocytes in lymphoid tissue.
AB  - Lymphoid tissue was examined to see whether in vivo cytopathic effects of human
      immunodeficiency virus (HIV) infection on lymphocytes could be detected.
      Transmission electron microscopy of mechanical suspensions prepared from lymph
      nodes showed both replication and phagocytosis of HIV particles by macrophages.
      Phagosomes contained cellular debris and virions, some of which were undergoing
      digestion. Neutrophils also contained HIV particles intermixed with cellular
      debris in phagosomes. Immunohistochemistry revealed whole Gag p24-positive
      lymphocytes and p24-positive cellular debris within the cytoplasm of paracortical
      macrophages. Lysing p24-positive lymphocytes were also seen. In the paracortex,
      p24-positive multinucleated lymphocytes with up to 5 nuclei were seen. In situ
      hybridization for HIV RNA in combination with immunohistochemistry for HAM56, a
      macrophage-specific marker, revealed colabeled cells. Thus, HIV-positive
      lymphocytes undergo lysis in lymphoid tissue. The cellular debris is phagocytized
      by macrophages, which themselves can replicate HIV. HIV-positive lymphocytes fuse
      in lymph nodes to form multinucleated cells.

PMID- 10882622
TI  - Effects of clinically used antioxidants in experimental pneumococcal meningitis.
AB  - Reactive oxygen intermediates mediate brain injury in bacterial meningitis.
      Several antioxidant drugs are clinically available, including N-acetylcysteine
      (NAC), deferoxamine (DFO), and trylizad-mesylate (TLM). The present study
      evaluated whether these antioxidants are beneficial in a model of pneumococcal
      meningitis. Eleven-day-old rats were infected intracisternally with Streptococcus
      pneumoniae and randomized to intraperitoneal treatment every 8 h with NAC (200
      mg/kg), DFO (100 mg/kg), TLM (10 mg/kg), or saline (250 microL). TLM-treated
      animals showed a significantly reduced mortality compared with controls (P<.03).
      Meningitis led to extensive cortical injury at 22+/-2.2 h after infection
      (median, 14. 6% of cortex; range, 0-61.1%). Injury was significantly (P<.01)
      reduced to 1.1% (range, 0-34.6%) by NAC, to 2.3% (range, 0-19.6%) by DFO, and to
      0.2% (range, 0-36.9%) by TLM (the difference was not significant among the 3
      groups). None of the drugs reduced hippocampal injury. Thus, several clinically
      used antioxidants reduced cortical injury in experimental pneumococcal
      meningitis.

PMID- 10882621
TI  - Endotoxin down-modulates granulocyte colony-stimulating factor receptor (CD114)
      on human neutrophils.
AB  - During infection, the development of nonresponsiveness to granulocyte colony
      stimulating factor (G-CSF) may be influenced by the down-modulation of G-CSF
      receptor (G-CSFR) by cytokines. This down-modulation was studied during
      experimental human endotoxemia. Healthy volunteers received either 2 ng/kg
      endotoxin (lipopolysaccharide [LPS], n=20) or placebo (n=10) in a randomized,
      controlled trial. Endotoxin infusion increased the mean fluorescence intensity of
      the neutrophil activation marker CD11b >300% after 1 h (P<.001 vs. placebo). LPS
      infusion down-modulated G-CSFR expression in as early as 60 min (-17%; P=.001 vs.
      placebo). Down-modulation was almost maximal at 90 min and persisted for 6 h (
      50% from baseline; P<.0001 vs. placebo). Plasma levels of G-CSF started to
      increase only after G-CSFR down-modulation had occurred and peaked 37-fold above
      baseline at 4 h (P<.0001 vs. placebo). In conclusion, LPS down-modulates G-CSFR
      expression in humans, which may render neutrophils less responsive to the effects
      of G-CSF and, thereby, compromise host defense mechanisms.

PMID- 10882623
TI  - Screening for Staphylococcus epidermidis markers discriminating between skin
      flora strains and those responsible for infections of joint prostheses.
AB  - Fifty-four Staphylococcus epidermidis strains responsible for infections of joint
      prostheses and 23 strains isolated from skin flora were studied for markers of
      virulence, to discriminate invasive strains from normal flora. They were screened
      for binding to polystyrene and matrix proteins and for the presence of
      staphylococcal genes involved in adhesion. The ica operon involved in biofilm
      formation was the only marker discriminating between these 2 categories of
      strains.

PMID- 10882624
TI  - Effect of quinupristin/dalfopristin on production of cytokines by human
      monocytes.
AB  - The effect of the novel streptogramin antibiotic quinupristin/dalfopristin
      (synercid) on cytokine production in vitro was examined in monocytes obtained
      from healthy human volunteers and stimulated with either lipopolysaccharide or
      heat-killed Staphylococcus aureus (Pansorbin). Synercid at concentrations that
      are achievable in humans (1, 5, and 10 microgram/mL) significantly suppressed
      production of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, granulocyte
      macrophage colony-stimulating factor, and tumor necrosis factor-alpha in a
      concentration-dependent manner. Thus, synercid possesses significant
      immunomodulatory activity, in addition to its antimicrobial activity.

PMID- 10882625
TI  - Prevalence of methicillin-resistant and methicillin-susceptible Staphylococcus
      aureus in the community.
AB  - Recent reports indicate that community-acquired methicillin-resistant
      Staphylococcus aureus (MRSA) infections are increasing and may now involve
      persons without risk factors predisposing for acquisition. To estimate the extent
      of community MRSA in New York City, the prevalence of S. aureus and MRSA nasal
      colonization in a well-patient population of 500 children and guardians was
      determined. The prevalence of S. aureus nasal carriage was 35% for children and
      28% for guardians. One person with predisposing risk factors was colonized with
      an MRSA, which was identified as the predominant clone found in New York City
      hospitals. A high degree of methicillin-susceptible S. aureus strain diversity
      was noted, with no apparent selection for specific clonal types. Thus, MRSA
      colonization is not ubiquitous in persons without predisposing risk outside of
      the health care environment. Bacterial competition and a lack of strong selection
      may limit the community spread of MRSA and can account for its sporadic
      distribution.

PMID- 10882626
TI  - The role of RANTES in meningococcal disease.
AB  - The chemokine RANTES (regulated on activation, normal T cell expressed and
      secreted) is a potent regulator of leukocyte trafficking. RANTES preferentially
      attracts mature CD4 cells as well as macrophages and eosinophils, but not
      neutrophils. In total, 128 children with meningococcal disease were prospectively
      studied, and the role of RANTES in the pathophysiology of meningococcal disease
      was assessed. Plasma RANTES, interleukin (IL)-8, IL-6, IL-1 receptor agonist, and
      tumor necrosis factor-alpha were measured at admission. Severity of disease was
      stratified by the Glasgow meningococcal septicemia prognostic score (GMSPS).
      RANTES levels correlated significantly with IL-8 levels, admission lactate
      levels, platelets, prothrombin time, and activated partial thromboplastin time.
      RANTES levels were lower in children with severe disease (GMSPS>/=8; P=.001), in
      those with septic shock (P<.0005), and in nonsurvivors (P=.048; Mann-Whitney
      test). RANTES is a potential mediator in the pathophysiology of meningococcal
      disease.

PMID- 10882627
TI  - CD4 alphabeta T lymphocytes express high levels of the T lymphocyte antigen CTLA
      4 (CD152) in acute malaria.
AB  - The role of T lymphocytes in human acute malaria remains under debate. The
      kinetics of T cell activation in acute malaria were investigated, with emphasis
      on CTLA-4 (CD152). In patients with malaria, CTLA-4 expression by CD4 alphabeta T
      lymphocytes was highly increased. After initiation of antiplasmodial treatment,
      it returned to control values within a few days. gammadelta T cells, which also
      are implicated in the pathogenesis of human malaria, did not express CTLA-4. The
      level of CTLA-4 expression at the time of hospital admission was correlated
      positively with other markers of disease severity-the peak of the parasitemia and
      the peak of serum neopterin levels. These results show that CTLA-4 is a sensitive
      and dynamic marker for T lymphocyte activation. Its strong increase in acute
      malaria argues for the involvement of T cells in the human immune response to
      plasmodia.

PMID- 10882629
TI  - Reply

PMID- 10882628
TI  - Blinded, placebo-controlled trial of antiparasitic drugs for trichinosis
      myositis.
AB  - There is no consensus on the benefits of treatment with any specific
      anthelminthic compound on muscle-stage trichinosis. A double-blind, placebo
      controlled comparison was done of 3 antiparasitic drugs during an outbreak of
      trichinosis in Chiangrai Province, northern Thailand. Forty-six adults were
      randomized to receive 10 days of oral treatment with mebendazole (200 mg twice a
      day), thiabendazole (25 mg/kg twice a day), fluconazole (400 mg initially, then
      200 mg daily), or placebo. All patients received treatment to eradicate adult
      intestinal worms. Trichinella spiralis infection was proved parasitologically in
      19 (41%) of 46 patient and by serodiagnosis in all cases. Significantly more
      patients improved after treatment with mebendazole (12/12) and thiabendazole
      (7/7) than after treatment with placebo (6/12; P<.05) or fluconazole (6/12).
      Muscle tenderness resolved in more patients treated with thiabendazole and
      mebendazole than in those treated with placebo (P<.05). However, 30% of
      volunteers could not tolerate the side effects of thiabendazole. In summary,
      Trichinella myositis responds to thiabendazole and to mebendazole.

PMID- 10882630
TI  - Detection of cytomegalovirus late (pp150) antigen in peripheral blood leukocytes
      of patients with human immunodeficiency virus-related lymphoma.

PMID- 10882631
TI  - Sex and shedding of human immunodeficiency virus.

PMID- 10882632
TI  - Reply

PMID- 10882634
TI  - Reply

PMID- 10882633
TI  - Possible mechanism for positive interaction of human T cell leukemia type I on
      liver disease in a hepatitis C virus-infected Japanese cohort.

PMID- 10882635
TI  - Waterborne outbreak of microsporidiosis.

PMID- 10882636
TI  - Reply

PMID- 10882637
TI  - Co-morbidity in Gaucher's disease results of a nationwide enquiry in Spain.
AB  - SHORT INTRODUCTION: Gaucher's disease (GD) is an autosomal recessive disease
      produced by mutations of the Glucocerebrosidase gene. Carriers are considered to
      be healthy subjects because there is no manifestation of the disease, but they
      show signs of macrophage disfunction. The aim of the study was to determine if GD
      patients and non affected carriers risk suffering other diseases when compared to
      healthy non-carrier relatives. MATERIAL AND METHODS:  DESIGN: Epidemiologic study
      of historic cohorts. The fact that they have one or two mutated alleles has been
      considered to be the risk factor leading to other conditions (Dementia, Parkinson
      disease, Ischemic stroke, Ischemic heart disease, Non rheumatic valvular disease,
      Cancer hematological and non-hematological, Pulmonary fibrosis, Tuberculosis,
      Gallstones and Schizophrenia). All people, patients, carriers and healthy
      controls shared the same genetical background and environmental influence. -
      Patients and relatives enrolled on the Spanish Gaucher Disease Registry were
      evaluated. STATISTICS: For the Relative-Risk calculation the Mantel-Haenszel test
      was applied. Yates' correction was used when size sample was too small. A value
      of p <0.05 was accepted for statistical significance. RESULTS: 370 people, from
      79 different families, were surveyed. We received evaluable information from 45
      families (56%), totalling 258 people (69%): 59 healthy subjects (Mean age 32. 20,
      RANGE: 10-85; M 57.63%/F 42.37%), 132 carriers (Mean age 35.91, RANGE: 1-79; M
      56.82%/F 43.18%) and 67 patients (Mean age 32.16, Range: 1-76; M 44.78%/F 55.22%.
      - Relative Risk of suffering any disease with regard to Gaucher's status: Patient
      vs Healthy 9.69 (95% Confidence interval [CI] 2.00-63.99; p 0.0006). Patient vs
      Carrier 3.74 (CI 1.53-9.27; p 0.001); Carrier vs Healthy 2.59 (CI 0. 52-12.50; p
      0.21). Relative Risk of suffering any disease with regard to sex was 3.96 for
      female patients (CI 1.01-16.75; p 0.02) and 1.34 for female carriers (CI 0.27
      6.75; p = 0.68). CONCLUSION: As a group, Gaucher's patients seem to have a
      greater risk of suffering other common unrelated diseases than carriers or
      healthy relatives. This excess of risk is particularly higher among female
      patients and can not be explained in terms of differences in age. Carrier status
      doesn't seem to highten the risk of suffering other diseases.

PMID- 10882638
TI  - Spontaneous regression of HIV associated T-cell non-Hodgkin's lymphoma with
      highly active antiretroviral therapy.
AB  - A subcutaneous, T-phenotypic anaplastic large cell lymphoma (CD30/Ki1-positive,
      EBV positive) was diagnosed in a HIV-infected bisexual man. Without chemotherapy
      the patient had a sustained long-term remission of this tumor (more than three
      years) after the initiation of highly active antiretroviral therapy. By PCR
      analysis of T-cell receptor beta gene rearrangements the tumor was found to be
      oligoclonal. Improvement of cellular immune function by antiretroviral therapy is
      the only recognizable factor which may have led to tumor remission. This
      hypothesis is supported by parallels to EBV associated polyclonal
      lymphoproliferation in allogeneic transplantat recipients where regression of
      lymphoma can be induced by reducing immunosuppressive therapy.

PMID- 10882639
TI  - Cotinine effects on bile flow and biliary NNK elimination.
AB  - Nicotine and its major metabolite cotinine inhibit alpha-hydroxylation of the
      tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
      suggesting that an alternative pathway of NNK metabolism and elimination, biliary
      excretion of the O-glucuronide of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol
      (NNAL-Gluc) may be enhanced. To verify the possible role of cotinine on biliary
      elimination of NNK and its metabolites, bile duct cannulated rats were
      administered a single i.p. dose of 50 mg/kg [56sup;-3 H]-NNK with or without i.p.
      co-administration of 5 mg/kg cotinine or nicotine. Cotinine significantly reduced
      cumulative bile flow and biliary elimination of NNK-derived radioactivity within
      six hours to 42 and 27 percent, respectively. The pattern of NNK metabolites in
      bile was unchanged. Nicotine had a similar inhibitory effect on bile flow. This
      result constitutes the first experimental evidence that cotinine inhibits bile
      flow. In rats, biliary elimination of NNK is reduced accordingly which may lead
      to an increased carcinogen burden in the body. In humans, inhibition of bile flow
      by tobacco alkaloids may contribute to the appetite suppressing effect of tobacco
      products.

PMID- 10882640
TI  - Addison-disease - an unusual clinical manifestation of CMV-end organ disease in
      pediatric AIDS.
AB  - CMV infection is common in pediatric HIV-1 infected patients. We present a case
      report, to our knowledge the first pediatric patient, in which Addison-disease
      due to CMV was suspected during lifetime. We want to point out the importance of
      routine clinical and laboratory follow up once a HIV-1 infected child is shown to
      be infected with CMV.

PMID- 10882641
TI  - Evaluation of the contents of mineral water, spring water, table water and spa
      water.
AB  - The present study surveys and evaluates the mineral contents of the speciality
      drinking waters currently available in Germany. A total of 257 producers and 226
      reports of water contents have been consulted. The minerals sodium, calcium,
      potassium and magnesium together with the halogens chlorine and fluorine have
      been of special interest here in view of their significance in infant feeding,
      caries prevention, and possible influence on the drinking waters, the sodium
      concentrated from 0.9 mg/l (Finkenbachquelle, mineral water) to 12830 mg/l (Bad
      Mergentheimer Albertquelle, spa water). The potassium values also, range broadly,
      between 1.4 mg/l (Kisslegger Sprudel, mineral water) and 611 mg/l (Obenauer
      Lowensprudel, mineral water). Fluoride concentrations were given special
      attention, since they are of significance in caries prevention, for the strength
      of bones, and also considerable importance in connection with the danger of
      fluorosis. Numerous commercial mineral waters and table waters contain too little
      fluoride (0.007 mg/l, Kirkeler Waldquelle, mineral water) or have fluoride
      concentrations over 4.1 mg/l (Hardenstein Brunnen, mineral water). The latter
      appear inappropriate, especially for small children. On the basis of the
      considerable variations of mineral and halogen contents in commercial mineral
      waters and table waters, the concentration of crucial trace elements should be
      clearly stated on the labels of the bottles, along with relevant information
      concerning possible effects.

PMID- 10882642
TI  - Glycyl-glutamine improves in vitro lymphocyte proliferation in AIDS patients.
AB  - BACKGROUND: Glutamine (Gln) is a major nutrient for rapidly proliferating cells.
      Unlike glutamine itself, the dipeptide glycyl-glutamine as a source for Gln is
      stable in aqueous solutions ex vivo. In order to evaluate the possible
      therapeutic role of glycyl-glutamine on lymphocyte proliferation we investigated
      its influence on lymphocytes of AIDS patients and healthy controls under
      stimulation with different mitogens. MATERIAL AND METHODS: Lymphocytes were
      collected from 11 adult patients suffering from AIDS according to the CDC
      definition and from 7 adult healthy donors. Glutamine (Gln) and glycyl-glutamine
      (GlyGln), respectively, were added to cell cultures at concentrations between 0
      and 1.0 mmol/l. ConA or SAC served as T or B cell mitogens, respectively. Plasma
      amino acid levels were determined. RESULTS: Proliferation upon ConA-stimulation
      with GlyGln-supplementation was similar to Gln-supplementation and peaked dose
      dependently at 1.0 mmol/l. When SAC was used Gln seemed slightly superior to
      GlyGln with a peak at 0. 4 mmol/l but the results did not reach the level of
      statistical significance. An identical response pattern was demonstrated in HIV
      patients, however at lower absolute proliferation rates. Normal values could not
      be restored. Overall, the use of either source of glutamine in equimolar
      concentrations did not result in major differences of proliferation. Glutamine
      and glycin plasma levels did not differ between HIV patients and controls.
      CONCLUSION: GlyGln can be used as a substitute for Gln with regard to lymphocyte
      proliferation. Lymphocytes from AIDS patients show, as controls do, an enhanced
      proliferation under supplementation either glutamine source. Supplementation of
      GlyGln might enhance lymphocyte proliferation and thus improve immunity.

PMID- 10882643
TI  - The correlation of office blood pressure and 24-hour ambulatory measurements in
      hypertensive patients - comparison between non-pharmacological treatment and
      antihypertensive medication.
AB  - Blood pressure control in many hypertensive patients remains imperfect, also
      because routine office blood pressure can only give limited information about
      diurnal variations and nocturnal dipping. It was the aim of our evaluation to
      study the efficacy of antihypertensive therapy and the correlation between
      repeated office blood pressure values and 24-hour ambulatory measurements in
      hypertensive outdoor patients treated by life-style modification and
      antihypertensive medication. Clinical data and blood pressure values in 343
      outdoor patients who were admitted to the medical centre for diagnostic and
      therapeutic procedures in hypertension were evaluated. Database was created from
      1991 to 1998. The study population (mean age 59.5 +/- 11.6 years) comprised 153
      men and 190 women, 141 (41%) were treated by life-style modification, 202 (59%)
      received antihypertensive medication. 57 patients showed symptoms of a metabolic
      syndrome, 62 suffered from manifest diabetes mellitus type 2. - Repeated office
      blood pressure measurements showed a significant positive correlation to the
      systolic and diastolic values obtained by 24-hour blood controls. While diastolic
      night minima revealed a positive correlation to office measurements (R = 0. 211;
      P <0.05), systolic night minima showed no correlation to office pressure control.
      In the whole study population and in subgroups (metabolic syndrome, diabetes
      mellitus) patients under antihypertensive medication still revealed significantly
      higher mean 24-hour systolic blood pressure values (140.5 +/- 16.9 mm Hg) than
      patients treated by life-style modification (133.0 +/- 14.4 mm Hg; P <0.001).
      Diastolic day- and night-time difference (dipping) was less pronounced in
      patients with antihypertensive medication. For appropriate antihypertensive
      therapy 24-hour blood pressure measurements are thus of advantage to repeated
      office controls especially to optimize medication for high systolic blood
      pressure values and adapt therapy to the nocturnal decrease of blood pressure
      values (dipping).

PMID- 10882644
TI  - Modulation of CD95 in leukemia and lymphoma cells by retinoids.
AB  - Retinoids are highly active for the treatment of acute promyelocytic leukemia,
      but have effects on many different types of normal and transformed cells. CD95 is
      a member of the TNF-receptor superfamily and can mediate apoptosis. In this
      study, we screened a series of 7 myeloid and 12 lymphoid cell lines for the
      expression of CD95 and for the induction of CD95 by retinoids. A differential
      response was observed: in 3/7 myeloid cell lines a significant down-regulation of
      CD95 happened which correlated with the induction of differentiation. A
      significant induction of CD95 was observed in 4/ 12 lymphoid lines (2 HHV8+ cell
      lines, one Burkitt line and another lymphoma line). The modulation of CD95 was
      both time- and dose- dependent (maximum reached after 3-5 days of culture with 10
      6 M retinoid). The 3 retinoid compounds studied (all-trans retinoic acid, 9-cis
      retinoic acid and 13-cis retinoic acid) had comparable activity. Taken together,
      we describe a new mode of induction of CD95 in lymphoma cells. More work is
      needed to define the functional consequences of these changes in CD95 surface
      expression.

PMID- 10882645
TI  - Clinical manifestations of tick-borne infections in children.

PMID- 10882646
TI  - Species-specific monoclonal antibodies to Escherichia coli-expressed p36
      cytosolic protein of Mycoplasma hyopneumoniae.
AB  - The p36 protein of Mycoplasma hyopneumoniae is a cytosolic protein carrying
      species-specific antigenic determinants. Based on the genomic sequence of the
      reference strain ATCC 25934, primers were designed for PCR amplification of the
      p36-encoding gene (948 bp). These primers were shown to be specific to M.
      hyopneumoniae since no DNA amplicons could be obtained with other mycoplasma
      species and pathogenic bacteria that commonly colonize the porcine respiratory
      tract. The amplified p36 gene was subcloned into the pGEX-4T-1 vector to be
      expressed in Escherichia coli as a fusion protein with glutathione S-transferase
      (GST). The GST-p36 recombinant fusion protein was purified by affinity
      chromatography and cut by thrombin, and the enriched p36 protein was used to
      immunize female BALB/c mice for the production of anti-p36 monoclonal antibodies
      (MAbs). The polypeptide specificity of the nine MAbs obtained was confirmed by
      Western immunoblotting with cell lysates prepared from the homologous strain.
      Cross-reactivity studies of the anti-p36 MAbs towards two other M. hyopneumoniae
      reference strains (ATCC 25095 and J strains) and Quebec field strains that had
      been isolated in culture suggested that these anti-p36 MAbs were directed against
      a highly conserved epitope, or closely located epitopes, of the p36 protein. No
      reactivity was demonstrated against other mycoplasma species tested. Clinical
      signs and lesions suggestive of enzootic pneumonia were reproduced in specific
      pathogen-free pigs infected experimentally with a virulent Quebec field strain
      (IAF-DM9827) of M. hyopneumoniae. The bacteria could be recovered from lung
      homogenates of pigs that were killed after the 3-week observation period by both
      PCR and cultivation procedures. Furthermore, the anti-p36 MAbs permitted
      effective detection by indirect immunofluorescence of M. hyopneumoniae in frozen
      lung sections from experimentally infected pigs. However, attempts to use the
      recombinant p36 protein as an antigen in an indirect enzyme-linked immunosorbent
      assay for the detection of antibodies in sera from convalescent pigs showed no
      correlation with clinical and pathological findings.

PMID- 10882647
TI  - Reactivity to p52 and CM2 recombinant proteins in primary human cytomegalovirus
      infection with a microparticle agglutination assay.
AB  - We evaluated the reactivities of sera against p52 and CM2 recombinant antigens of
      human cytomegalovirus (HCMV), coated on microparticles, for the differentiation
      of primary HCMV infection from an established infection. Two different test
      formats of the CMV Multiplex Copalis assay were evaluated. The 214 serum samples
      tested were immunoglobulin M (IgM) positive or equivocal by our reference assay.
      Reactivities against p52 and CM2 antigens were tested for sera from 37 patients
      with a well-documented seroconversion within the preceding 3 months (119 serum
      specimens), 31 patients known to have had a seroconversion at least 8 months
      earlier (31 serum specimens), and 57 patients without a documented seroconversion
      (64 serum specimens). The assay had a sensitivity for the detection of a primary
      infection of 70 or 86% by the first test format and a sensitivity of 88 or 94% by
      the second test format, according to the criteria used to indicate a primary
      infection by this test. A good correlation of the results of the assay with our
      in-house avidity index was found. The specificity of the assay warrants further
      evaluation. With IgM-positive sera, the assay was not sufficiently specific to
      make a distinction between a primary infection and an established infection.

PMID- 10882649
TI  - Immunological diagnosis of human hydatid cyst relapse: utility of the enzyme
      linked immunoelectrotransfer blot and discriminant analysis.
AB  - A discriminant technique was applied to the different serological patterns
      obtained by enzyme-linked immunoelectrotransfer blotting (EITB) and by
      conventional immunological tests, in order to differentiate the residual antibody
      patterns present in healed hydatidosis from the ones present in patients with
      active hydatidosis. For this purpose, specific antibodies against Echinococcus
      granulosus were detected by indirect hemagglutination, agglutination of latex
      particles, basophil degranulation, and EITB for 23 patients with active
      hydatidosis and 45 patients with surgically cured hydatidosis. Discriminant
      analysis of the different serological patterns obtained by EITB and conventional
      serology correctly classified 92.54% of patients (93.3% if the patients are
      differentiated according to the time elapsed since surgery). This method detected
      the presence of active hydatidosis in 95.6% of patients for whom abdominal
      ultrasonography had confirmed the presence of active hydatid cysts. The global
      specificity was 88.9%. The specificity was 97.1% for patients who had been
      operated on 3 years ago or more and 63.6% for patients with less time since
      surgery.

PMID- 10882648
TI  - Need for an external proficiency testing program for cytokines, chemokines, and
      plasma markers of immune activation.
AB  - An external evaluation program for measuring the performance of laboratories
      testing for cytokines and immune activation markers in biological fluids was
      developed. Cytokines, chemokines, soluble cytokine receptors, and other soluble
      markers of immune activation (CSM) were measured in plasma from a healthy human
      immunodeficiency virus (HIV)-seronegative reference population and from HIV
      seropositive individuals as well as in supernatant fluids from in vitro
      stimulated human immune cells. The 14 components measured were tumor necrosis
      factor (TNF) alpha, gamma interferon, interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL
      10, Rantes, MIP-Ia, MIP-Ibeta, soluble TNF receptor II, soluble IL-2 receptor
      alpha, beta(2)-microglobulin, and neopterin. Twelve laboratories associated with
      the Adult and Pediatric AIDS Clinical Trial Groups participated in the study. The
      performance features that were evaluated included intralaboratory variability,
      interlaboratory variability, comparison of reagent sources, and ability to detect
      CSM in the plasma of normal subjects as well as the changes occurring in disease.
      The principal findings were as follows: (i) on initial testing, i.e., before
      participating in the program, laboratories frequently differed markedly in their
      analytic results; (ii) the quality of testing of a CSM in individual
      participating laboratories could be assessed; (iii) most commercial kits allowed
      distinction between normal and abnormal plasma CSM levels and between
      supernatants of stimulated and unstimulated cells; (iv) different sources of
      reagents and reference standards frequently provided different absolute values;
      (v) inexperienced laboratories can benefit from participating in the program;
      (vi) laboratory performance improved during active participation in the program;
      and (vii) comparability between analyses conducted at different sites can be
      ensured by an external proficiency testing program.

PMID- 10882650
TI  - Superantigens and cystic fibrosis: resistance of presenting cells to
      dexamethasone.
AB  - Staphylococcus aureus, a common pulmonary pathogen in cystic fibrosis (CF),
      produces exotoxins that are extremely potent superantigens. A number of animal
      studies have shown that superantigens cause pulmonary inflammation, but the
      possible role of superantigens in CF has not been investigated. The present study
      assessed possible differences between control and CF B cells in presenting
      superantigens to T cells. Immortalized B-cell lines were used as superantigen
      presenting cells to avoid environmental influences (e.g., infection or
      antibiotics) common to freshly isolated cells. The results show that CF B-cell
      lines presented a staphylococcal superantigen to the immortalized T-cell line
      (Jurkat) as effectively as did control B-cell lines as measured by interleukin-2
      production. However, in contrast to the case for control B-cell lines,
      dexamethasone did not inhibit CF B-cell lines from presenting superantigen. The
      resistance of superantigen-presenting CF B cells to corticosteroids suggests that
      the pulmonary response to superantigens may be poorly regulated in CF, leading to
      an exaggerated inflammatory response to S. aureus.

PMID- 10882651
TI  - Cloning of the bovine immunodeficiency virus gag gene and development of a
      recombinant-protein-based enzyme-linked immunosorbent assay.
AB  - An enzyme-linked immunosorbent assay (ELISA) was established for the rapid
      detection of specific bovine immunodeficiency virus (BIV) antibodies in cattle,
      using recombinant Gag protein as an antigen. The gag coding region from BIV was
      cloned into an expression vector, pQE32, which expressed high levels of
      recombinant protein from Escherichia coli. The ELISA was standardized by a
      checkerboard titration against known BIV-positive and -negative sera from cattle
      and a monoclonal antibody to the Gag protein. A total of 139 cattle serum
      samples, from the diagnostic laboratory at Kansas State University, Manhattan,
      and from the Dairy Station, Louisiana State University, Baton Rouge, were
      compared by ELISA and immunoblot assays for the detection of BIV-specific
      antibodies. Of 26 cattle sera samples which tested positive using the immunoblot
      assay, 23 were positive by ELISA, thus establishing a strong correlation between
      the two tests. The sensitivity and specificity of ELISA relative to
      immunoblotting were 0.88 and 0.93, respectively. ELISA proved to be as specific
      as immunoblotting but was much less time-consuming and easier to perform.

PMID- 10882652
TI  - Development of monoclonal antibodies against Ureaplasma urealyticum serotypes and
      their use for serotyping clinical isolates.
AB  - Monoclonal antibodies (MAbs) against Ureaplasma urealyticum serotype 2, 5, 7, 8,
      10, 11, 12, and 13 reference strains were developed. The reactivities of these
      MAbs with the 14 serotype reference strains was verified by colony
      immunofluorescence assay and Western blot assay. MAbs against serotypes 2, 7, 10,
      11, and 12 were serotype specific, whereas MAbs against serotypes 5, 8, and 13
      showed cross-reactivity. All MAbs against serotype 5 were cross-reactive with
      serotype 2, and one showed, in addition, cross-reactivity to serotypes 9 and 10.
      Mutual cross-reactivities were observed between MAbs against serotypes 8 and 13.
      The usefulness of the MAbs for the serotyping of U. urealyticum strains was
      evaluated by serotyping 21 selected clinical isolates. A complete set of MAbs
      (the newly developed MAbs and the previously described MAbs against serotypes 1,
      3, 4, 6, 9, and 14) as well as a complete set of polyclonal antibodies (PAbs),
      PAbs 1 to 14, were used. MAbs were able to identify 18 of 21 isolates including 2
      isolates with mixed serotypes. Polyreactivity, which occurred with 19 of the 21
      isolates with PAbs, was not observed by the use of MAbs. MAbs seem to be a more
      valuable tool than PAbs for serotyping and could help in investigating a possible
      link between the expression or variability of the serotype-specific antigens and
      pathogenicity.

PMID- 10882653
TI  - Primary structure of the sialodacryoadenitis virus genome: sequence of the
      structural-protein region and its application for differential diagnosis.
AB  - Sialodacryoadenitis virus (SDAV) is a coronavirus that is commonly found in
      laboratory rats and that causes sialodacryoadenitis and respiratory illness. We
      cloned and sequenced the 3' terminal 9.8 kb of the genomic RNA and analyzed the
      structure of the viral genome. As with mouse hepatitis coronaviruses (MHVs), the
      SDAV genome was able to code for a spike protein, a small membrane protein, a
      membrane-associated protein, and a nucleocapsid protein. In addition, the
      hemagglutinin-esterase gene capable of encoding a protein of 439 amino acids (aa)
      was identified. The putative functional site for acetylesterase activity was
      present in the HE protein as Phe-Gly-Asp-Ser (FGDS), suggesting that the SDAV HE
      protein might have retained the esterase activity. Immediately upstream of the HE
      gene and downstream of the polymerase 1b gene, the NS2 nonstructural-protein gene
      was identified with a coding capacity of 274 aa. A motif of UCUAAAC was
      identified as a potential transcription signal for subgenomic mRNA synthesis.
      Large insertions of 172, 127, and 44 aa were detected in the N-terminal half of
      the predicted S protein of SDAV when its sequence was compared to the sequences
      of MHV 2, MHV JHM, and MHV A59, respectively. The sequence information on the
      SDAV S-protein gene was applied to a differential diagnostic PCR to detect and
      distinguish the rat coronavirus from mouse coronaviruses. This is the first
      report on the comprehensive genetic information of any rat coronavirus.

PMID- 10882654
TI  - Antibody to heat shock protein can be used for early serological monitoring of
      Helicobacter pylori eradication treatment.
AB  - Infection with Helicobacter pylori induces humoral immune responses against
      various antigens of the bacterium. Heat shock proteins (hsps) are immunodominant
      antigens in various diseases including H. pylori infection. In the present study,
      we measured the anti-hsp antibody titers in 42 patients with H. pylori-infected
      peptic ulcers during a bacterial eradication study. The patients were treated
      with a proton pump inhibitor and antimicrobial agents to eradicate the organism.
      Their sera were obtained at pretreatment and at 1 month and 6 months after the
      eradication therapy. The titers of immunoglobulin G antibodies to the H. pylori
      hsp, whole-cell lysate, and urease (30-kDa subunit) antigens in serum were
      measured by a capture enzyme-linked immunosorbent assay. The levels of H. pylori
      hsp60 antibodies in sera collected 1 month after treatment had declined
      significantly, even when changes in the titers of antibodies to whole-cell and
      urease antigens were not apparent. These results suggest that measurement of
      antibodies to H. pylori hsp60 in serum is useful for the early monitoring of the
      effectiveness of eradication therapy.

PMID- 10882655
TI  - Ethyleneglycol-bis-(beta-aminoethylether)tetraacetate as a blood anticoagulant:
      preservation of antigen-presenting cell function and antigen-specific
      proliferative response of peripheral blood mononuclear cells from stored blood.
AB  - We examined the progressive and irreversible loss of antigen-specific
      lymphoproliferative responses in peripheral blood mononuclear cells (PBMC)
      obtained from blood exposed for prolonged periods to EDTA as an anticoagulant.
      The responses of these lymphocytes to interleukin-2 or to concanavalin A were,
      however, unaffected. The observed loss was not due to depletion of metal ions by
      EDTA, since the addition of several divalent cations to whole blood during
      storage in EDTA or to lymphocytes from EDTA-stored blood during antigen
      stimulation in vitro did not alleviate the defect. Reconstitution of antigen
      specific T-cell lines or Percoll-purified T cells with adherent antigen
      presenting cells in antigen stimulation assays revealed that the presenting cells
      and not the effector T-cells were the targets of EDTA-mediated damage. The
      anticoagulant heparin helped to circumvent this problem. Surprisingly, EGTA,
      another metal ion chelator, could successfully replace EDTA, with a marginal loss
      in antigen-specific responses. Lymphoproliferative responses to antigens of
      Japanese encephalitis virus (JEV) and Mycobacterium tuberculosis were both
      significantly preserved in EGTA. JEV antigen-specific responses of PBMC obtained
      from the blood of convalescent JEV patients and stored in EGTA for as long as 24
      h (n = 20) were comparable to those of fresh PBMC (n = 10), while PBMC from blood
      stored in EDTA (n = 17) for 16 h or longer failed to respond. We recommend that
      EGTA be used as the anticoagulant of choice for applications that require the
      lymphocyte proliferation assay, especially when on-site testing facilities are
      not available.

PMID- 10882656
TI  - Serologic testing for celiac disease in the United States: results of a
      multilaboratory comparison study.
AB  - The aim of this study was to compare the efficiencies of six reference
      laboratories for serologic testing for celiac disease. Serum from 20 patients
      with untreated celiac disease and from 20 controls was thawed, divided, and
      distributed to each participating laboratory, which performed endomysial antibody
      tests. Five laboratories also performed antigliadin antibody tests. Sensitivity
      for endomysial antibody immunoglobulin A (IgA) varied from 57 to 90%. In all
      laboratories, the specificity for celiac disease was 100%. The sensitivity and
      specificity for both IgA and IgG antigliadin antibody varied significantly. When
      results from all three tests were combined in each laboratory, sensitivity was 90
      to 100%. The specificity for endomysial antibody was 100% in the laboratories.
      Sensitivity was less than reported previously. Standardization of these tests is
      needed in the United States.

PMID- 10882657
TI  - Antigenic and genetic characterization of lipoprotein LppQ from Mycoplasma
      mycoides subsp. mycoides SC.
AB  - Lipoprotein LppQ, a predominant 48-kDa antigen, and its corresponding gene, lppQ,
      were characterized in Mycoplasma mycoides subsp. mycoides SC, the etiological
      agent of contagious bovine pleuropneumonia. The lppQ gene is specific to M.
      mycoides subsp. mycoides SC and was found in the type strain and in field strains
      isolated in Europe, Africa, and Australia, as well as in vaccinal strains. LppQ
      is encoded as a precursor with a consensus sequence for prokaryotic signal
      peptidase II and a lipid attachment site. The leader sequence shows significant
      prominent transmembrane helix structure with a predicted outside-to-inside helix
      formation capacity. The N-terminal domain of the mature LppQ was shown to be
      surface exposed. It induced a strong, specific, early, and persistent immune
      response in naturally and experimentally infected animals. The C-terminal domain
      of LppQ possesses an integral membrane structure built up of repeated units, rich
      in hydrophobic and aromatic amino acids, which have a pore formation potential. A
      recombinant peptide representing the N-terminal domain of LppQ was obtained by
      site-directed mutagenesis of nine Mycoplasma-specific TGA (Trp) codons into
      universal TGG (Trp) codons and expression in Escherichia coli hosts. It was used
      for serodetection of cattle infected with M. mycoides subsp. mycoides SC, in
      which it was detected postinfection for significantly longer than conventional
      serological test reactions.

PMID- 10882658
TI  - Enhancement by ampicillin of antibody responses induced by a protein antigen and
      a DNA vaccine carried by live-attenuated Salmonella enterica serovar Typhi.
AB  - Live-attenuated Salmonella species are effective carriers of microbial antigens
      and DNA vaccines. In a mouse model, the immunoglobulin M (IgM) and total antibody
      levels directed toward the lipopolysaccharide of Salmonella enterica serovar
      Typhi were significantly enhanced at day 21 after oral immunization with live
      attenuated serovar Typhi (strain Ty21a) when ampicillin was concomitantly
      administered (P < 0.05 and P < 0.005, respectively). The heat-killed Ty21a
      stimulated lymphocyte proliferation indices for the ampicillin group at day 21
      were significantly higher than those for the normal saline (NS) group (P < 0.005,
      P < 0.001, and P < 0.01) for all three doses of antigen (10(4), 10(5), and 10(6)
      heat-killed Ty21a per well, respectively). The 50% lethal doses for mice from the
      ampicillin and NS groups immunized with Ty21a with pBR322 after wild-type serovar
      Typhi challenge on day 24 were 3.4 x 10(7) and 5.0 x 10(6) CFU, respectively. The
      fecal bacterial counts for the ampicillin group at days 1, 3, and 5 were
      significantly lower than those for the NS group (P < 0.01, P < 0.01, and P <
      0.05, respectively), and there was a trend toward recovery of Ty21a in a larger
      number of mice from the ampicillin group than from the NS group. Furthermore, the
      IgG2a levels directed toward tetanus toxoid were significantly enhanced at days 7
      and 21 after oral immunization with Ty21a that carried the fragment c of tetanus
      toxoid when ampicillin was concomitantly administered (P < 0.05 and P < 0.005,
      respectively), and the IgM and total hepatitis B surface antibody levels were
      significantly enhanced at days 7 (P < 0.005 and P < 0.05, respectively) and 21 (P
      < 0.01 and P < 0.05, respectively) after oral immunization with Ty21a that
      carried the DNA vaccine that encodes hepatitis B surface antigen when ampicillin
      was concomitantly administered. The present observation may improve the efficacy
      of the protein antigens and DNA vaccines carried in live-attenuated bacteria, and
      further experiments should be carried out to determine the best antibiotics and
      dosage regimen to be used, as well as the best carrier system for individual
      protein antigens and DNA vaccines.

PMID- 10882659
TI  - Cloning and expression of immunoreactive antigens from Mycobacterium
      tuberculosis.
AB  - Four immunoreactive proteins, B.4, B.6, B.10, and B.M, with molecular weights
      ranging from 16,000 to 58,000, were observed from immunoblots of Mycobacterium
      tuberculosis total lysates screened with sera from individuals with active
      tuberculosis. These proteins were identified from microsequence analyses, and
      genes of proteins with the highest homology were PCR amplified and cloned into
      the pQE30 vector for expression studies. In addition, a 37.5-kDa protein,
      designated C17, was identified from a phage expression library of M. tuberculosis
      genomic DNA. Preliminary immunoblot assays indicated that these five resultant
      recombinant proteins could detect antibodies in individuals with active pulmonary
      and extrapulmonary tuberculosis. The overall ranges of sensitivities,
      specificities, positive predictive values, and negative predictive values for the
      recombinant antigens were 20 to 58, 88 to 100, 69 to 100, and 56 to 71%,
      respectively. The B.6 antigen showed preferential reactivity to antibodies in
      pulmonary compared to nonpulmonary tuberculosis serum specimens. All of these
      recombinant antigens demonstrated potential for serodiagnosis of tuberculosis.

PMID- 10882660
TI  - Enzyme-linked immunosorbent assays using the recombinant dense granule antigens
      GRA6 and GRA1 of Toxoplasma gondii for detection of immunoglobulin G antibodies.
AB  - The potential of the dense granule antigens GRA1 and GRA6 of Toxoplasma gondii to
      be used as diagnosis reagents in a recombinant form was evaluated. Both proteins
      were expressed in Escherichia coli as glutathione-S-transferase (GST) fusions.
      The GST-GRA1 fusion comprises the entire GRA1 sequence devoid of its N-terminal
      signal peptide. Separate expression of the two N- and C-terminal hydrophilic
      regions of GRA6 showed that only the N-terminal hydrophilic part of the protein
      was recognized by a pool of positive human sera in an immunoblot. One hundred T.
      gondii-positive and 98 negative human sera were tested in two separate
      immunoglobulin G (IgG)-direct enzyme-linked immunosorbent assays (ELISAs) using
      either GST-GRA1 or GST-GRA6-Nt recombinant protein. Whereas the sensitivity of
      the GST-GRA1 IgG ELISA was low (68%), the GST-GRA6-Nt IgG ELISA reached a
      sensitivity of 96%. The reactivity to GRA6-Nt was shown to be high even with
      human sera of low IgG titers. In addition, comparison of the optical density
      values for each serum revealed that GRA1 may complement GRA6-Nt to reach an
      overall sensitivity of 98%. Therefore, the GST-GRA6-Nt ELISA could be used
      together with another antigen like GRA1 for the development of a recombinant
      antigen-based test for serodiagnosis of toxoplasmosis.

PMID- 10882661
TI  - Serological differentiation of murine typhus and epidemic typhus using cross
      adsorption and Western blotting.
AB  - Differentiation of murine typhus due to Rickettsia typhi and epidemic typhus due
      to Rickettsia prowazekii is critical epidemiologically but difficult
      serologically. Using serological, epidemiological, and clinical criteria, we
      selected sera from 264 patients with epidemic typhus and from 44 patients with
      murine typhus among the 29,188 tested sera in our bank. These sera cross-reacted
      extensively in indirect fluorescent antibody assays (IFAs) against R. typhi and
      R. prowazekii, as 42% of the sera from patients with epidemic typhus and 34% of
      the sera from patients with murine typhus exhibited immunoglobulin M (IgM) and/or
      IgG titers against the homologous antigen (R. prowazekii and R. typhi,
      respectively) that were more than one dilution higher than those against the
      heterologous antigen. Serum cross-adsorption studies and Western blotting were
      performed on sera from 12 selected patients, 5 with murine typhus, 5 with
      epidemic typhus, and 2 suffering from typhus of undetermined etiology.
      Differences in IFA titers against R. typhi and R. prowazekii allowed the
      identification of the etiological agent in 8 of 12 patients. Western blot studies
      enabled the identification of the etiological agent in six patients. When the
      results of IFA and Western blot studies were considered in combination,
      identification of the etiological agent was possible for 10 of 12 patients. Serum
      cross-adsorption studies enabled the differentiation of the etiological agent in
      all patients. Our study indicates that when used together, Western blotting and
      IFA are useful serological tools to differentiate between R. prowazekii and R.
      typhi exposures. While a cross-adsorption study is the definitive technique to
      differentiate between infections with these agents, it was necessary in only 2 of
      12 cases (16.7%), and the high costs of such a study limit its use.

PMID- 10882662
TI  - Differentiation of Bartonella species by a microimmunofluorescence assay, sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, and Western immunoblotting.
AB  - Bartonella species can be differentiated by microimmunofluorescence assay, sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and immunoblotting
      with murine polyclonal antisera to Bartonella henselae, B. quintana, B.
      elizabethae, and B. bacilliformis. A pairwise comparison on the basis of SDS-PAGE
      protein profiles demonstrated similarity values for proteins of different
      Bartonella species ranging from 28.6 to 86.4%. Antigenic relationships revealed
      by immunoblotting with murine antisera were equivalent to those of proteins
      observed by SDS-PAGE. A dendrogram obtained on the basis of protein bands of SDS
      polyacrylamide gels showed that Bartonella species could be divided into three
      groups. B. bacilliformis was distinct from all other Bartonella species; B.
      grahamii, B. taylorii, B. doshiae, and B. vinsonii formed a cluster, as did B.
      henselae, B. quintana, B. elizabethae, and B. clarridgeiae. These relationships
      were consistent with those revealed by parsimony trees derived from 16S rRNA and
      gltA gene sequencing. SDS-PAGE analysis showed that 120-, 104-, 85-, 71-, 54-, 47
      , 40-, 33-, 30-, and 19-kDa proteins were present in all species, with the 54-kDa
      protein being the most dominant. Proteins with a molecular mass of less than 54
      kDa allow the differentiation of species and are a possible target for future
      species-specific antibodies and antigens.

PMID- 10882663
TI  - Parasporin, a human leukemic cell-recognizing parasporal protein of Bacillus
      thuringiensis.
AB  - An unusual property, human leukemic cell-recognizing activity, associated with
      parasporal inclusions of a noninsecticidal Bacillus thuringiensis soil isolate
      was investigated, and a protein (named parasporin in this study) responsible for
      the activity was cloned. The parasporin, encoded by a gene 2,169 bp long, was a
      polypeptide of 723 amino acid residues with a predicted molecular weight of 81,
      045. The sequence of parasporin contained the five conserved blocks commonly
      found in B. thuringiensis Cry proteins; however, only very low homologies (<25%)
      between parasporin and the existing classes of Cry and Cyt proteins were
      detected. Parasporin exhibited cytocidal activity only when degraded by proteases
      into smaller molecules of 40 to 60 kDa. Trypsin and proteinase K activated
      parasporin, while chymotrypsin did not. The activated parasporin showed strong
      cytocidal activity against human leukemic T cells (MOLT-4) and human uterus
      cervix cancer cells (HeLa) but not against normal T cells.

PMID- 10882664
TI  - Angiotensin II increases host resistance to peritonitis.
AB  - Studies by other laboratories have shown that angiotensin II (AII) can affect the
      function of cells which comprise the immune system. In the present study, the
      effect of AII on the function of peritoneal macrophages and peripheral blood
      monocytes was assessed. In vitro exposure (4 h prior to assay) of peritoneal
      macrophages from mice and rats to AII increased the percentage of cells that
      phagocytosed opsonized yeast and the number of yeast per macrophage. Furthermore,
      AII increased the respiratory burst capacity of peritoneal macrophages from mice
      and rats and peripheral blood mononuclear cells from humans. Because of these
      observations, the effect of AII on host resistance to bacterial infection was
      assessed. Intraperitoneal administration of AII was shown to increase host
      resistance (reduced abscess formation) in an animal model of bacterial
      peritonitis. Studies were then conducted to assess whether parenteral
      administration of AII, a clinically relevant route, could affect peritoneal host
      resistance in a manner similar to that observed after peritoneal administration.
      These studies showed that subcutaneous administration of AII throughout the
      postinfection interval increased the level of host resistance to bacterial
      peritonitis. Furthermore, in a study which compared AII and Neupogen, an agent
      approved for use for the reduction of febrile neutropenia after myeloablative
      therapy, daily subcutaneous administration of AII reduced abscess size and
      incidence, whereas Neupogen did not have any therapeutic benefit in this model.
      These data suggest that AII may be of therapeutic benefit as an immunomodulatory
      agent.

PMID- 10882665
TI  - Comparison of a monoclonal antibody-blocking enzyme-linked immunoassay and a
      strip immunoblot assay for identifying type-specific herpes simplex virus type 2
      serological responses.
AB  - Detection of herpes simplex virus type 2 (HSV-2)-specific antibodies by a
      monoclonal antibody (MAb)-blocking enzyme-linked immunoassay (EIA) was compared
      with detection by a strip immunoblot assay (SIA) in a sexually transmitted
      disease (STD) clinic population. The study population consisted of 1,683
      genitourinary medicine clinic attendees (582 women and 1,101 men). Sera were
      tested for the presence of HSV-2 antibody by use of the blocking EIA, in which
      binding of the MAb AP-1 to HSV-2 glycoprotein G-2 (gG-2) is blocked by HSV-2
      specific antibody. The Chiron RIBA HSV-1 and -2 strip immunoassay (SIA) utilizes
      HSV-1- and HSV-2-specific or cross-reactive antigens immobilized on
      nitrocellulose strips (HSV gB-1 and HSV gG-1 peptide bands specific for HSV-1
      antibody, HSV-2 gG-2 band specific for HSV-2 antibody, and HSV gD-2 band cross
      reactive for HSV-1 and HSV-2 antibodies). A total of 1,612 sera were tested by
      MAb-blocking EIA for HSV-2 antibody and by SIA for HSV-1 and HSV-2 antibodies. By
      EIA, 541 (33.6%) sera were positive for HSV-2 antibody and 1,068 sera were
      negative for HSV-2 antibody; 3 sera gave equivocal results. HSV-2 antibody was
      detected in 555 (34.4%) sera by SIA; 144 (26%) of these sera possessed only HSV-2
      antibody, and 411 (74%) sera contained both HSV-1 and HSV-2 antibodies. SIA
      detected HSV-1 antibody in 1,155 (71.6%) sera; 744 (64%) of these sera contained
      HSV-1 antibody alone. Sixteen sera contained antibody against HSV but could not
      be typed by SIA. A total of 512 sera were positive for HSV-2 antibody by both the
      EIA and SIA. We concluded that the blocking EIA and SIA showed a high level of
      agreement in detecting HSV-2 antibody in this population. In contrast to the SIA,
      the blocking EIA is a useful tool for large epidemiological studies, though the
      SIA proved to be slightly more sensitive once sera with discrepant results were
      further tested.

PMID- 10882666
TI  - Antigenic properties and diagnostic potential of baculovirus-expressed infectious
      bursal disease virus proteins VPX and VP3.
AB  - The routine technique for detecting antibodies specific to infectious bursal
      disease virus (IBDV) is a serological evaluation by enzyme-linked immunosorbent
      assay (ELISA) with preparations of whole virions as the antigens. To avoid using
      complete virus in the standard technique, we have developed two new antigens
      through the expression of the VPX and VP3 genes in insect cells. VPX and
      especially VP3 were expressed at high levels in insect cells and simple to
      purify. The immunogenicity of both proteins was similar to that of the native
      virus. VPX was able to elicit neutralizing antibodies but VP3 was not. Purified
      VPX and VP3 were tested in an indirect ELISA with more than 300 chicken sera.
      There was an excellent correlation between the results of the ELISA using VPX and
      those of the two commercial kits. VP3 did not perform as well as VPX, and the
      linear correlation was significantly lower. A comparison with the standard
      reference technique, seroneutralization, showed that the indirect ELISA was more
      sensitive. Therefore, VPX-based ELISA is a good alternative to conventional
      ELISAs that use whole virions.

PMID- 10882667
TI  - Comparison of two recombinant major outer membrane proteins of the human
      granulocytic ehrlichiosis agent for use in an enzyme-linked immunosorbent assay.
AB  - Enzyme-linked immunosorbent assay (ELISA) for human granulocytic ehrlichiosis
      (HGE) using two different recombinant P44 proteins (rP44 and rP44-2hv) of the HGE
      agent as antigens was evaluated. Sera from a total of 72 healthy humans both from
      regions where HGE is nonendemic and regions where HGE is endemic were used as
      negative controls to determine the cutoff value for ELISA. Sera from a total of
      14 patients (nine from whom the HGE agent was isolated and five who were HGE-PCR
      positive) were used as positive controls. One hundred nine sera from 72 patients
      in an area where HGE is endemic who were suspected of having HGE were examined by
      ELISA and indirect immunofluorescence assay (IFA). All IFA-negative sera were
      negative by both ELISAs. Of 39 sera that were IFA positive, 35 and 27 were
      positive by ELISA using rP44 and rP44-2hv, respectively, indicating that the use
      of rP44 is more sensitive. Western blot analysis of the four rP44-ELISA-negative
      IFA-positive sera using whole HGE agent as antigen suggests that these four sera
      were false IFA positive. There was no difference in results with or without the
      preabsorption of sera with Escherichia coli or with or without the cleavage of
      the fused protein derived from the vector. There was a significant positive
      correlation between IFA titers and optical densities of ELISAs. Four Ehrlichia
      chaffeensis-positive and 10 Borrelia burgdorferi-positive sera were negative by
      ELISA. However, two Babesia microti-positive sera showed strong cross-reactivity
      to the fused vector protein, which was eliminated after cleavage of the protein.
      Thus, ELISA using rP44 nonfusion protein would provide a simple, specific, and
      objective HGE serologic test which can be easily automated.

PMID- 10882668
TI  - Use of synthetic cardiolipin and lecithin in the antigen used by the venereal
      disease research laboratory test for serodiagnosis of syphilis.
AB  - The Venereal Disease Research Laboratory (VDRL) test is a microflocculation test
      for syphilis that uses an antigen containing cardiolipin, lecithin, and
      cholesterol. For more than 50 years, the preparation of natural cardiolipin and
      lecithin for this test has been based on the Pangborn method which involves
      isolating and purifying these components from beef hearts. This process is
      tedious and time-consuming and results in a variable purity range. In our
      studies, we found that a VDRL antigen using synthetic tetramyristoyl cardiolipin
      and synthetic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (lecithin) was as
      specific in detecting syphilis as a VDRL antigen made with natural components. In
      85% of the cases, we obtained an endpoint titer of 1/2 or 1 dilution more than a
      titer obtained with a VDRL antigen made with natural components. The use of these
      pure synthetic compounds, with a purity of 99%, would offer advantages in the
      standardization and stability of the VDRL antigen. Because this antigen is the
      basic ingredient in the preparation of nontreponemal reagents such as the rapid
      plasma reagin, toluidine red unheated serum test, and the unheated serum reagin,
      the use of this synthetic VDRL antigen should also increase the reactivity of
      these reagents.

PMID- 10882669
TI  - Serodiagnostic potential of culture filtrate antigens of Mycobacterium
      tuberculosis.
AB  - Our studies of the humoral responses of tuberculosis (TB) patients have defined
      the repertoire of culture filtrate antigens of Mycobacterium tuberculosis that
      are recognized by antibodies from cavitary and noncavitary TB patients and
      demonstrated that the profile of antigens recognized changes with disease
      progression (K. Samanich et al., J. Infect. Dis. 178:1534-1538, 1998). We have
      identified several antigens with strong serodiagnostic potential. In the present
      study we have evaluated the reactivity of cohorts of human immunodeficiency virus
      (HIV)-negative, smear-positive; HIV-negative, smear-negative; and HIV-infected TB
      patients, with three of the candidate antigens, an 88-kDa protein, antigen (Ag)
      85C, and MPT32, and compared the reactivity of the same patient cohort with the
      38-kDa antigen and Ag 85A. We have also compared the reactivity of native Ag 85C
      and MPT32 with their recombinant counterparts. The evaluation of the reactivity
      was done by a modified enzyme-linked immunosorbent assay described earlier (S.
      Laal et al., Clin. Diag. Lab. Immunol. 4:49-56, 1997), in which all sera are
      preadsorbed against Escherichia coli lysates to reduce the levels of cross
      reactive antibodies. Our results demonstrate that (i) antigens identified on the
      basis of their reactivity with TB patients' sera provide high sensitivities for
      serodiagnosis, (ii) recombinant Ag 85C and MPT32, expressed in E. coli, show
      reduced reactivity with human TB sera, and (iii) of the panel of antigens tested,
      the 88-kDa protein is the most promising candidate for serodiagnosis of TB in HIV
      infected individuals. Moreover, these results reaffirm that both the extent of
      the disease and the bacterial load may play a role in determining the antigen
      profile recognized by antibodies.

PMID- 10882670
TI  - A Limulus antilipopolysaccharide factor-derived peptide exhibits a new
      immunological activity with potential applicability in infectious diseases.
AB  - Previous studies have shown that cyclic peptides corresponding to residues 35 to
      52 of the Limulus antilipopolysaccharide (anti-LPS) factor (LALF) bind and
      neutralize LPS-mediated in vitro and in vivo activities. Therapeutic approaches
      based on agents which bind and neutralize LPS activities are particularly
      attractive because these substances directly block the primary stimulus for the
      entire proinflammatory cytokine cascade. Here we describe new activities of the
      LALF(31-52) peptide, other than its LPS binding ability. Surprisingly,
      supernatants from human mononuclear cells stimulated with the LALF peptide are
      able to induce in vitro antiviral effects on the Hep-2 cell line mediated by
      gamma interferon (IFN-gamma) and IFN-alpha. Analysis of the effect of LALF(31-52)
      on tumor necrosis factor (TNF) and nitric oxide (NO) production by LPS-stimulated
      peritoneal macrophages revealed that a pretreatment with the peptide decreased
      LPS-induced TNF production but did not affect NO generation. This indicates that
      the LALF peptide modifies the LPS-induced response. In a model in mice with
      peritoneal fulminating sepsis, LALF(31-52) protected the mice when administered
      prophylactically, and this effect is related to reduced systemic TNF-alpha
      levels. This study demonstrates, for the first time, the anti-inflammatory
      properties of the LALF-derived peptide. These properties widen the spectrum of
      the therapeutic potential for this LALF-derived peptide and the molecules derived
      from it. These agents may be useful in the prophylaxis and therapy of viral and
      bacterial infectious diseases, as well as for septic shock.

PMID- 10882671
TI  - Evaluation of human FcgammaRIIA (CD32) and FcgammaRIIIB (CD16) polymorphisms in
      Caucasians and African-Americans using salivary DNA.
AB  - Two classes of low-affinity receptors for the Fc region of immunoglobulin G (IgG)
      (FcgammaR) are constitutively expressed on resting human neutrophils. These
      receptors, termed FcgammaRIIa (CD32) and FcgammaRIIIb (CD16), display biallelic
      polymorphisms which have functional consequences with respect to binding and/or
      ingestion of targets opsonized by human IgG subclass antibodies. The H131-R131
      polymorphism of CD32 influences binding of human IgG2 and, to a lesser extent,
      human IgG3 to neutrophils. The neutrophil antigen (NA1-NA2) polymorphism of CD16
      influences the efficiency of phagocytosis of bacteria opsonized by human IgG1 and
      IgG3. These polymorphisms may influence host susceptibility to certain infectious
      and/or autoimmune diseases, prompting interest in the development of facile
      methods for determination of CD32 and CD16 genotype in various clinical settings.
      We previously reported that genomic DNA from saliva is a suitable alternative to
      DNA from blood in PCR-based analyses of CD32 and CD16 polymorphisms. In the
      present study, we utilized for the first time this salivary DNA-based methodology
      to define CD32 and CD16 genotypes in 271 Caucasian and 118 African-American
      subjects and to investigate possible linkage disequilibrium between certain CD32
      and CD16 genotypes in these two ethnic groups. H131 and R131 gene frequencies
      were 0.45 and 0.55, respectively, among Caucasians and 0.59 among African
      Americans. NA1 and NA2 gene frequencies were 0.38 and 0.62 among Caucasians and
      0. 39 and 0.61 among African-Americans. Since FcgammaRIIa and FcgammaRIIIb
      synergize in triggering neutrophils, we also assessed the frequency of different
      CD32 and CD16 genotype combinations in these two groups. In both groups, the
      R/R131-NA2/NA2 genotype combination was more common than the H/H131-NA1/NA1
      combination (threefold for Caucasians versus sevenfold for African-Americans).
      Whether individuals with the combined R/R131-NA2/NA2 genotype are at greater risk
      for development of infectious and/or autoimmune diseases requires further
      investigation, which can be conveniently performed using DNA from saliva rather
      than blood.

PMID- 10882672
TI  - Effects of androgen treatment on expression of macrophage Fcgamma receptors.
AB  - Macrophage Fcgamma receptors (FcgammaRs) play an important role in the host
      defense against infection and in the pathophysiology of immune cytopenias.
      Modulation of macrophage FcgammaR expression is a potential therapeutic approach
      to immune disorders. Glucocorticoids and progesterones decrease macrophage
      FcgammaR expression. We assessed the effect of treatment with androgens and
      antiandrogens on the expression of macrophage FcgammaRs using an experimental
      guinea pig model. Four androgens (testosterone, dihydrotestosterone, mesterolone,
      and danazol) and five antiandrogens (flutamide, nilutamide, cyproterone acetate,
      spironolactone, and finasteride) were studied. Following in vivo treatment of
      guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized
      erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated
      splenic macrophages, and splenic macrophage FcgammaR cell surface expression. All
      of the androgens impaired the clearance of IgG-sensitized erythrocytes by
      decreasing splenic macrophage FcgammaR expression. Dihydrotestosterone and
      mesterolone were more effective than testosterone or dihydrotestosterone. Flow
      cytometry and fluorescence microscopy with monoclonal antibodies demonstrated
      that the androgens decreased the cell surface expression of FcgammaR1,2 more than
      that of FcgammaR2. Antiandrogens did not significantly alter macrophage FcgammaR
      expression. Nevertheless, antiandrogens counteracted the effects of androgens on
      macrophage FcgammaR expression. These data indicate that androgens impair the
      clearance of IgG-coated cells by decreasing splenic macrophage FcgammaR
      expression. Thus, androgens other than danazol are candidate drugs for the
      treatment of immune disorders.

PMID- 10882673
TI  - Nonradioactive techniques for measurement of in vitro T-cell proliferation:
      alternatives to the [(3)H]thymidine incorporation assay.
AB  - T-cell proliferation is an important in vitro parameter of in vivo immune
      function and has been used as a prognostic marker of human immunodeficiency virus
      type 1 (HIV-1) disease progression. The proliferative capacity of T cells in
      response to various stimuli is commonly determined by a radioactive assay based
      on incorporation of [(3)H]thymidine ([(3)H]TdR) into newly generated DNA. In
      order to assess techniques for application in laboratories where radioactive
      facilities are not present, two alternative methods were tested and compared to
      the [(3)H]TdR assay as a "gold standard." As an alternative, T-cell proliferation
      was measured by flow cytometric assessment of CD38 expression on T cells and by
      an enzyme-linked immunosorbent assay (ELISA) based on bromo-2'-deoxyuridine
      (BrdU) incorporation. Peripheral blood mononuclear cells (PBMCs), either in whole
      blood or Ficoll-Isopaque separated, from a total of 26 HIV-1-positive and 18 HIV
      1-negative Dutch individuals were stimulated with CD3 monoclonal antibody (MAb)
      alone, a combination of CD3 and CD28 MAbs, or phytohemagglutinin. BrdU
      incorporation after 3 days of stimulation with a combination of CD3 and CD28 MAbs
      correlated excellently with the [(3)H]TdR incorporation in both study groups (HIV
      1 positives, r = 0.96; HIV-1 negatives, r = 0.83). A significant correlation of
      absolute numbers of T cells expressing CD38 with [(3)H]TdR incorporation, both in
      HIV-1-positive (r = 0.96) and HIV-1-negative (r = 0.84) individuals, was also
      observed under these conditions. The results of this study indicate that
      determination of both the number of CD38-positive T cells and BrdU incorporation
      can be used as alternative techniques to measure the in vitro T-cell
      proliferative capacity. The measurement of CD38 expression on T cells provides
      the additional possibility to further characterize the proliferating T-cell
      subsets for expression of other surface markers.

PMID- 10882674
TI  - Decreased levels of CD54 (ICAM-1)-positive lymphocytes in the peripheral blood in
      untreated patients with active juvenile dermatomyositis.
AB  - Significant abnormalities are observed in the peripheral blood of juvenile
      dermatomyositis (JDM) patients with active disease. In this study, we confirm
      that there is a significant increase in the relative percentage of B lymphocytes
      in the peripheral blood of a group of untreated children with newly diagnosed
      active JDM compared to healthy children (P < 0.0001). In order to investigate if
      properties intrinsic to B cells contributed to their relative increase in JDM,
      the percentage of B cells expressing activation markers (CD23, CD25, CD54, and
      CD69) was measured and compared to pediatric controls. Compared to healthy
      children less than 10 years of age (not significantly different from the JDM
      group), the JDM patients had an increase in the proportion of lymphocytes
      expressing CD19 (B cells; P = 0.0017) and decreases in the percentage of
      lymphocytes that were CD3(-) CD16(+) and/or CD56(+) (NK cells; P = 0. 01) and
      CD3(+) CD8(+) (T suppressor/cytotoxic cells; P = 0.02). There were no significant
      differences in any of the B-cell activation markers assessed. Of note, the
      percentage of CD54(+) non-B lymphocytes (i.e., T cells and NK cells expressing
      CD54) was significantly lower in the JDM patients (25% +/- 5%) than in the "age
      related" healthy control group (43% +/- 4%; P = 0.013). These results suggest the
      following for untreated children with active JDM: (i) the increase in the
      percentage of peripheral blood B cells is not due to intrinsic B-cell activation,
      and (ii) CD54/ICAM-1(+) non-B cells, CD8(+) T cells, and NK cells are being
      removed from circulation and may be participating in the pathophysiology of the
      disease.

PMID- 10882675
TI  - Diagnosis of human immunodeficiency virus type 1 infection with different
      subtypes using rapid tests.
AB  - We evaluated six rapid tests for their sensitivity and specificity in diagnosing
      human immunodeficiency virus type 1 (HIV-1) infection using 241 specimens (172
      HIV-1 positive, 69 HIV-1 negative) representing different HIV-1 subtypes (A [n =
      40], B [n = 47], C [n = 28], E [n = 42], and F [n = 7]). HIVCHEK, Multispot, RTD
      and SeroStrip were 100% sensitive and specific. Capillus failed to identify two
      of eight subtype C specimens (overall sensitivity of 98. 85%), while the SUDS
      test (the only test approved by the Food and Drug Administration) gave false
      positive results for 5 of 69 seronegative specimens (specificity of 93.24%). Our
      results suggest that although rapid tests perform well in general, it may be
      prudent to evaluate a rapid test for sensitivity and specificity in a local
      population prior to its widespread use.

PMID- 10882676
TI  - Development of a recombinant nucleoprotein-based enzyme-linked immunosorbent
      assay for quantification of antibodies against porcine reproductive and
      respiratory syndrome virus.
AB  - A rapid, inexpensive enzyme-linked immunosorbent assay (ELISA) to quantitate
      antibodies to porcine respiratory and reproductive syndrome virus (PRRSV) in
      serum was developed using a recombinant PRRSV nucleoprotein (rN). The sensitivity
      (85.3%) and specificity (81.7%) of the Kansas State University ELISA were good,
      correlating well (82.4%) with the IDEXX HerdChek ELISA.

PMID- 10882677
TI  - Lack of utility of specific immunoglobulin G antibody avidity for serodiagnosis
      of reactivated toxoplasmosis in immunocompromised patients.
AB  - The avidities of Toxoplasma-specific immunoglobulin G serum antibodies were
      measured in immunocompromised patients presenting with cerebral or extracerebral
      toxoplasmosis and/or serological reactivation. Since avidity remained high and
      stable in 39 of 40 patients with toxoplasmosis and 27 of 28 patients with
      serological reactivation, we conclude that this test cannot help diagnose
      toxoplasmosis in these patients.

PMID- 10882678
TI  - Serological detection of infection with diverse human and simian immunodeficiency
      viruses using consensus env peptides.
AB  - Cross-species transmission has been shown to play an important role in the
      emergence of human retroviruses. We developed a generic enzyme immunoassay using
      synthetic peptides from gp41 and C2V3 consensus sequences (human immunodeficiency
      virus [HIV] type 1 [HIV-1] groups M, O, and N and the homologous region of simian
      immunodeficiency virus [SIV] strains from chimpanzees [SIVcpz], SIVcpzGAB1 and
      SIVcpzANT) to detect divergent HIV and SIV. A cocktail of peptides from gp41 and
      C2V3 (M-O) detected all HIV-1 group M and O sera and showed cross-reactivity with
      SIVcpz sera. Further, a mixture of C2V3 peptides (GAB1-ANT) failed to detect HIV
      1 infections but reacted with all SIVcpz sera, allowing discrimination of SIVcpz
      from HIV-1 infections. Since most SIVcpz sera cross-reacted with HIV-1 peptides,
      we next evaluated SIVcpz serum reactivity with rapid tests for HIV-1/2. SIVcpzANT
      and SIVcpzUS sera reacted with the Sero-strip and Multispot assays. Both tests
      are sensitive in detecting group M (97 100%, respectively), although Multispot
      has lower sensitivity for group O detection (67%) than does Sero-strip (100%).
      The limited volume and time required to perform these assays make them a generic
      tool for field screening. The env peptide-based assay and rapid tests should
      allow for the identification of emerging variants of HIV and SIV.

PMID- 10882679
TI  - CD4(+) lymphocyte-mediated suppression of cytomegalovirus expression in human
      astrocytes.
AB  - Cytomegalovirus-stimulated CD4(+) lymphocytes from seropositive but not
      seronegative donors suppressed viral gene expression in primary human astrocytes.
      This suppressive activity was mediated through soluble factors. These findings
      suggest that CD4(+) lymphocytes play a role in defense of the brain against
      cytomegalovirus.

PMID- 10882680
TI  - Viability and functional activity of cryopreserved mononuclear cells.
AB  - Factors that influence viability and function of cryopreserved peripheral blood
      mononuclear cells (PBMC) were identified on 54 samples from 27 AIDS Clinical
      Trial Units. PBMC viability ranged from 1 to 96% with a median of 70%, was higher
      in laboratories with experienced staff, and was not significantly associated with
      CD4 cell number. Function of cryopreserved PBMC, measured by lymphocyte
      proliferation, was associated with viability. Preparations with viability greater
      than or equal to 70% had consistent proliferative responses and were suitable for
      functional analyses.

PMID- 10882681
TI  - New insights into the mechanism of action of lantibiotics--diverse biological
      effects by binding to the same molecular target.

PMID- 10882682
TI  - Epidemic salmonella typhimurium DT 104--a truly international multiresistant
      clone.

PMID- 10882683
TI  - Triclosan and antibiotic resistance in Staphylococcus aureus.
AB  - Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is an antimicrobial agent
      used in hygiene products, plastics and kitchenware, and for treating methicillin
      resistant Staphylococcus aureus (MRSA) outbreaks. S. aureus strains with low
      level resistance to triclosan have emerged. It has been claimed that strains with
      decreased susceptibility to biocides may also be less susceptible to antibiotics.
      We tested the susceptibility of S. aureus clinical isolates to triclosan and
      several antibiotics. Triclosan MICs ranged between 0.025 and 1 mg/L. Some, but
      not all, strains were resistant to several antibiotics and showed low-level
      triclosan resistance. S. aureus mutants with enhanced resistance to triclosan (<
      or =1 mg/L) were isolated. In several cases this resistance was stably inherited
      in the absence of triclosan. These mutants were not more resistant than the
      parent strain to several antibiotics. Changes in triclosan MICs associated with
      the acquisition of a plasmid encoding mupirocin resistance were not observed,
      suggesting that the triclosan/mupirocin co-resistance seen in a previous study
      was not the result of a single resistance gene or separate genes on the same
      plasmid. The continuous exposure of a triclosan-sensitive S. aureus strain to sub
      MIC concentrations of triclosan for 1 month did not result in decreased
      susceptibility to triclosan or to several antibiotics tested. Triclosan-induced
      potassium leakage and bactericidal effects on a triclosan-sensitive strain, a
      resistant strain and a strain selected for increased resistance were compared
      with those of non-growing organisms, exponentially growing organisms and
      organisms in the stationary phase. No significant differences between the strains
      were observed under these conditions despite their different MICs. Biocides have
      multiple target sites and so MICs often do not correlate with bactericidal
      activities. The ability of S. aureus to develop resistance to triclosan and the
      current view that triclosan may have a specific target in Escherichia coli,
      namely enoyl reductase, underline the need for more research on the mechanisms of
      action and resistance.

PMID- 10882684
TI  - Apoptosis, oxidative metabolism and interleukin-8 production in human neutrophils
      exposed to azithromycin: effects of Streptococcus pneumoniae.
AB  - Pathogen virulence factors and the host inflammatory response cause tissue injury
      associated with respiratory tract infections. The azalide azithromycin has
      demonstrated efficacy in the treatment of these infections. It has been
      demonstrated previously that induction of polymorphonuclear leucocyte (PMN)
      apoptosis is associated with minimization of tissue damage and inflammation in
      the lung. We hypothesized that, in addition to its antibacterial effects,
      azithromycin may promote apoptosis. The aim of the study was to determine the
      effects of azithromycin on PMN apoptosis, oxidative function and interleukin-8
      (IL-8) production in the presence or absence of Streptococcus pneumoniae, in
      comparison with penicillin, erythromycin, dexamethasone or phosphate-buffered
      saline. Human circulating PMNs were assessed for apoptosis (by annexin V
      labelling and ELISA), oxidative function (by nitroblue tetrazolium reduction) and
      IL-8 production (by ELISA). Azithromycin significantly induced PMN apoptosis in
      the absence of S. pneumoniae after 1 h (10.27% +/- 1.48%, compared with 2.19% +/-
      0.42% in controls) to levels similar to those after 3 h induction with tumour
      necrosis factor-alpha (8. 73% +/- 1.86%). This effect was abolished in the
      presence of S. pneumoniae. Apoptosis in PMNs exposed to the other drugs was not
      significantly different from that in controls. Azithromycin did not affect PMN
      oxidative metabolism or IL-8 production. In summary, azithromycin-induced PMN
      apoptosis may be detected in the absence of any effect on PMN function, and the
      pro-apoptotic properties of azithromycin are inhibited in the presence of S.
      pneumoniae.

PMID- 10882685
TI  - Emergence of resistance to biocides during differentiation of Acanthamoeba
      castellanii.
AB  - A synchronous encystment method was used to study the order of development of
      resistance of Acanthamoeba castellanii to a range of biocides. The emerging
      resistance during encystation to short-term exposure to the minimum amoebicidal
      concentrations of each biocide tested was recorded during the first 36 h of the
      differentiation process. Hydrochloric acid and moist heat were tested as possible
      resistance markers. Development of the acid-insoluble, proteincontaining,
      ectocyst wall and the cellulose endocyst wall was followed by quantification of
      the acid- and alkali-insoluble residues of cell samples removed from synchronous
      encystment cultures up to 36 h. Resistance to chemical agents (polyhexamethylene
      biguanide, benzalkonium chloride, propamidine isethionate, pentamidine
      isethionate, dibromopropamidine isethionate, hydrogen peroxide) and to moist heat
      was seen to develop between 14 and 24 h after trophozoites were inoculated into
      the encystment media. Resistance to hydrochloric acid developed between 0 and 2 h
      and to chlorhexidine diacetate between 24 and 36 h. Levels of acid-insoluble
      residues began to increase after 8 h and alkali-insoluble residues (cellulose)
      were detected after 16 h and coincided with the emergence of resistance to all
      the agents tested except hydrochloric acid. The results suggest that resistance
      to the biocides tested probably results largely from the physical barrier of the
      cyst walls rather than as a consequence of a metabolically dormant cyst.

PMID- 10882686
TI  - Pharmacodynamic studies of trovafloxacin and grepafloxacin in vitro against Gram
      positive and Gram-negative bacteria.
AB  - Grepafloxacin and trovafloxacin are two novel fluoroquinolones with extended Gram
      positive bacterial spectra compared with older quinolones. The aim of the present
      study was to investigate the different pharmacodynamic parameters of
      grepafloxacin in comparison with those of trovafloxacin. The following studies
      were performed against various Gram-positive and Gram-negative bacteria: (i)
      determination of the rate and extent of killing at a concentration corresponding
      to the 1 h non-protein-bound human serum level following an oral dose of 800 mg
      grepafloxacin and 300 mg trovafloxacin; (ii) determination of the rate and extent
      of killing of the two quinolones at different concentrations; (iii) determination
      of the post-antibiotic effects (PAEs); (iv) determination of the post-antibiotic
      sub-MIC effects (PA SMEs); (iv) determination of the rate and extent of killing
      in an in vitro kinetic model. It was shown that both grepafloxacin and
      trovafloxacin exhibited concentration-dependent killing against both Gram
      positive and Gram-negative bacteria. Grepafloxacin exhibited a slower
      bactericidal effect against all the Gram-positive strains investigated in
      comparison with trovafloxacin in spite of a similar C(max)/MIC in the static
      experiments and a similar AUC/MIC ratio in the kinetic experiments. No major
      differences in the extent and rate of killing were noted against the Gram
      negative strains, which were killed almost completely after 3 h except for
      Pseudomonas aeruginosa. A PAE of both quinolones was noted for all strains
      investigated. Trovafloxacin induced longer PAEs against the Gram-positive strains
      but shorter PAEs in comparison with those of grepafloxacin against the Gram
      negative strains. A prolonging of the PAEs was noted for all bacteria when
      exposed to sub-MICs in the post-antibiotic phase. With a similar AUC/MIC of 310
      for the penicillin-sensitive strain of Streptococcus pneumoniae and 143 for the
      penicillin-resistant strain, the time for 99.9% eradication for both strains was
      2 h for trovafloxacin and 6 h for grepafloxacin.

PMID- 10882687
TI  - The antimicrobial efficacy of a new central venous catheter with long-term broad
      spectrum activity.
AB  - Indwelling vascular catheters are a major cause of nosocomial sepsis. Prevention
      of colonization of polymeric surfaces by continuous release of bactericidal,
      highly biocompatible antimicrobials incorporated into polymers has been
      investigated as a promising new approach. An antimicrobial polyurethane catheter
      was investigated by HPLC and various antimicrobial assays. Controlled drug
      delivery governed by the physico-chemical mass transfer from the polyurethane
      bulk provided long-term release of the antimicrobial substances from the material
      to the outer surface and catheter lumen. The in vitro activity of catheters
      coated with miconazole and rifampicin against 158 clinical isolates of catheter
      associated infections was evaluated. Incubated in physiological NaCl at 37
      degrees C, the half-life of inhibitory activity of catheters coated with
      miconazole or rifampicin exceeded 3 weeks. In static and dynamic adhesion assays,
      coated catheters were able to prevent colonization with Staphylococcus aureus,
      Staphylococcus epidermidis and enterococci. To produce catheters resistant to
      infection, a potent antimicrobial efficacy combined with an excellent
      biocompatibility over time is needed. The long lasting efficacy of the
      antimicrobial polyurethane alloy as well as the increased antifungal activity of
      miconazole combined with rifampicin may be regarded as a promising improvement
      for long-term central venous access.

PMID- 10882688
TI  - Antibacterial effect of telithromycin (HMR 3647) and comparative antibiotics
      against intracellular Legionella pneumophila.
AB  - The activity of the ketolide telithromycin (HMR 3647) against intracellular
      Legionella pneumophila strain L-1033 was compared with the activities of
      erythromycin and levofloxacin. To assay intracellular antibacterial activity,
      human monocytes were allowed to adhere to wells in 24-well tissue culture plates
      and were then exposed to L. pneumophila cells for 1 h to allow phagocytosis to
      occur. Antibiotics were added to the wells after removal of unphagocytosed
      bacteria. Quantitative bacterial cell counts were made from lysed monocytes at 0,
      24, 48, 72 and 96 h. The antibacterial effects of antibiotics against
      intracellular L. pneumophila L-1033 were concentration and time dependent; at 10
      x MIC the activity of telithromycin was greater than that of erythromycin and was
      less than that of levofloxacin (P < 0.01); telithromycin-rifampicin combinations
      showed no synergy or interference; and removal of telithromycin from assays at 24
      h did not affect its intracellular antibacterial activity. In conclusion, the
      ketolide telithromycin has excellent activity against intracellular L.
      pneumophila strain L-1033 and should be evaluated for therapy of legionnaires'
      disease.

PMID- 10882689
TI  - Efficacy of nitazoxanide, tizoxanide and tizoxanide glucuronide against
      Cryptosporidium parvum development in sporozoite-infected HCT-8 enterocytic
      cells.
AB  - The effects of nitazoxanide and its metabolites, tizoxanide and tizoxanide
      glucuronide, on the development of the asexual and sexual stages of
      Cryptosporidium parvum in differentiated human enterocytic HCT-8 cells were
      evaluated in a quantitative alkaline phosphatase immunoassay. Nitazoxanide,
      tizoxanide and tizoxanide glucuronide were inhibitory for up to 46 h when added
      after sporozoite invasion (MIC50 1.2, 22.6 and 2.2 mg/L, respectively).
      Tizoxanide had only limited activity, but nitazoxanide and tizoxanide glucuronide
      strongly inhibited asexual and sexual stages, respectively.

PMID- 10882690
TI  - The effects of exposure at constant (1 h) or exponentially decreasing
      concentrations of quinupristin/dalfopristin on biofilms of Gram-positive
      bacteria.
AB  - Using a biofilm model, infections by Staphylococcus aureus, coagulase-negative
      staphylococci and enterococci were studied. The biofilms were exposed to
      quinupristin/dalfopristin and five comparator antibiotics: ciprofloxacin,
      vancomycin, teicoplanin, flucloxacillin and erythromycin. Two methods of exposure
      to the drugs were used: constant for 1 h, and exponentially decreasing, with the
      rate of dilution being matched to the half-lives of the antibiotics. The effects
      of antibiotic exposure were monitored by performing viable counts on the cells
      eluted from the biofilms. The results are presented as the inhibitory or
      bactericidal effect (the reduction in numbers of bacteria eluted from the
      biofilms) and recovery times (the time taken for the number of cells eluted from
      the biofilms to return to the number eluted before the drug exposure).
      Quinupristin/dalfopristin was the most effective of the six antibiotics studied,
      especially against enterococci. However, there were no significant differences in
      the effects, inhibitory/ bactericidal or recovery times, produced by the two
      methods of exposure. The two glycopeptides showed a surprising lack of activity.

PMID- 10882691
TI  - Combination therapy for chronic Pseudomonas aeruginosa respiratory infection
      associated with biofilm formation.
AB  - There had been no reports of investigations into biofilms in chronic respiratory
      infection in vivo. Recently, we established a new murine model of chronic
      respiratory infection with Pseudomonas aeruginosa. In the present study, we
      examined the bacteriological effect of combined clarithromycin and levofloxacin
      against chronic respiratory infection with P. aeruginosa. Scanning electron
      micrograph of the surface of the catheter intubated in mouse bronchus for 7 days
      demonstrated in vivo formation of a biofilm containing blood cells, complex
      fibrous structures and bacteria. Treatment with either clarithromycin alone or
      levofloxacin alone had no statistical effect on the number of viable bacteria in
      lung. The combined use of both drugs resulted in a significant decrease in the
      number of viable bacteria. The present experiment demonstrates that the newly
      established murine model was useful to investigate the treatment of biofilm
      associated chronic respiratory infection with P. aeruginosa, and combination
      therapy with clarithromycin and levofloxacin was effective in biofilm-associated
      chronic respiratory infection.

PMID- 10882692
TI  - Assessment of different antibacterial effect measures used in in vitro models of
      infection and subsequent use in pharmacodynamic correlations for moxifloxacin.
AB  - A dilutional culture in vitro pharmacodynamic model of infection was used to
      assess the best measure of antibacterial effect for moxifloxacin at simulated
      human doses of 400 mg 24 hourly for 48 h. This was then related to two
      pharmacodynamic parameters, the drug area under curve: MIC ratio (AUC/MIC) and
      the length of time that the drug concentration remained above the MIC of the
      bacterium (T > MIC). Twenty-one bacterial strains (Streptococcus pneumoniae n =
      6; Haemophilus influenzae n = 6; Moraxella catarrhalis n = 3; beta-haemolytic
      streptococci n = 3; Staphylococcus aureus n = 3; MIC range 0.06-3.6 mg/L) were
      tested in 69 individual simulations. The measures or parameters of antibacterial
      effect considered were log change in viable count in the initial inoculum at 12 h
      (triangle up12), 24 h (triangle up24), 36 h (triangle up36), 48 h (triangle
      up48), maximum reduction in count (triangle up(max)); time for bacterial counts
      to reduce by 100-fold from the initial density (T99) or 1,000-fold (T99.9); and
      area under the bacterial kill curve from 0 to 24 h (AUBKC(24)) or from 0 to 48 h
      (AUBKC(48)). triangle up12, triangle up24, triangle up36, triangle up48, triangle
      up(max), T99, T99.9 did not vary over the complete range of MICs; at high MICs,
      especially with Gram-positive bacteria the T99 and T99.9 values were >48 h while
      at low MICs, especially with Gram-negative bacteria, bacterial counts were
      reduced below the limit of detection with triangle up12, triangle up24, triangle
      up36, triangle up48 and triangle up(max) exceeding >6.5 log reduction. AUBKC(24)
      and AUBKC(48) varied more completely over the range of MICs and more importantly
      had the best within-strain reproducibility (median percentage coefficient of
      variation <15%). The relationship between the transformed AUBKC(24) and AUC/MIC
      could be described by a sigmoid Emax model but the relationship with T > MIC
      could not. Use of weighted least squares regression to examine the combined
      effect of AUC/MIC and T > MIC on AUBKC(24) indicated that AUC/MIC provided a good
      fit to the data (r(2) = 0.94) and adding T > MIC did not improve the model fit.
      Cox proportional hazards regression indicated that AUC/MIC was predictive of T99
      and in a multivariate model although AUC/MIC predicted outcome after fitting
      AUC/MIC, T > MIC was not significant. AUBKC was thus shown to be the optimum
      measure of antibacterial effect to use in pharmacodynamic studies of moxifloxacin
      and AUC/MIC the best predictor of antibacterial effect as measured by AUBKC(24)
      or T99. These results are in good agreement with animal data on moxifloxacin
      pharmacodynamics and human data for some other fluoroquinolones.

PMID- 10882693
TI  - Pharmacodynamics of vancomycin and ampicillin alone and in combination with
      gentamicin once daily or thrice daily against Enterococcus faecalis in an in
      vitro infection model.
AB  - We compared the pharmacodynamic activities of vancomycin and ampicillin with or
      without gentamicin once daily or thrice daily in an in vitro infection model with
      fibrin-platelet clots (FPCs) infected with Enterococcus faecalis. Antibiotics
      were administered as a bolus to simulate human pharmacokinetics with regimens
      consisting of vancomycin 1 g q12h, ampicillin 2 g q6h and gentamicin 1.3 mg/kg
      q8h and 5 mg/kg qd. Model experiments were performed in duplicate over 72 h. FPCs
      were removed from the models in triplicate at 0, 8, 24, 32, 48 and 72 h, weighed,
      homogenized, diluted and plated to determine colony counts. Additional FPCs were
      removed at over 72 h post-antibiotic dose to determine antibiotic concentrations.
      The inoculum density at 72 h was used to compare bactericidal activity between
      the regimens. Overall, all antibiotic regimens containing either ampicillin or
      vancomycin significantly (P < 0.01) decreased the bacterial load at 72 h compared
      with the growth control although monotherapy regimens with either vancomycin or
      gentamicin had little impact. Ampicillin was superior to vancomycin with or
      without the addition of gentamicin (P < 0.01). There were no significant
      differences in reduction of bacterial density at 72 h between the combination of
      ampicillin or vancomycin plus gentamicin q8h and ampicillin or vancomycin plus
      gentamicin once daily. This was despite achieving unmeasurable FPC gentamicin
      concentrations after the 8 h time point during the once-daily aminoglycoside
      regimen. Vancomycin plus gentamicin either every 8 h or once daily was
      significantly (P < 0.01) better than vancomycin alone. Ampicillin plus either of
      the two gentamicin regimens was also better than ampicillin alone but this did
      not reach statistical significance. Our data suggest that once-daily gentamicin
      in combination with ampicillin or vancomycin demonstrates equivalent bacterial
      reductions to combination therapy with thrice-daily gentamicin. Once-daily
      aminoglycoside combination therapy for the treatment of enterococcal endocarditis
      warrants further investigation.

PMID- 10882694
TI  - Two new gene cassettes, dfr17 (for trimethoprim resistance) and aadA4 (for
      spectinomycin/streptomycin resistance), inserted in an Escherichia coli class 1
      integron.
AB  - Two new gene cassettes, dfr17 and aadA4, inserted in a class 1 integron of
      Escherichia coli EC107, are described here. The dfr17 cassette encodes
      trimethoprim resistance and has 91% identity with the dfrVII dihydrofolate
      reductase gene. The aadA4 cassette confers resistance to spectinomycin and
      streptomycin and shows 94% identity with the aadA3 gene. The integron carrying
      the dfr17 and aadA4 cassettes was located on a conjugative plasmid, pEC1072.

PMID- 10882695
TI  - Effect of grepafloxacin on cytokine production in vitro.
AB  - The effect of a new quinolone antibacterial agent, grepafloxacin, on the
      production of cytokines was investigated using lipopolysaccharide-stimulated
      human peripheral blood cells. Grepafloxacin 1-30 mg/L inhibited the production of
      interleukin 1alpha (IL-1alpha) and IL-1beta, and the expression of IL-1alpha, IL
      1beta, tumour necrosis factor alpha (TNFalpha), IL-6 and IL-8 mRNA. These results
      suggest that the inhibitory effect of grepafloxacin is exerted, in part, at the
      gene transcription level.

PMID- 10882697
TI  - In vitro activity of DU-6681a, an active form of the new oral carbapenem compound
      DZ-2640, in comparison with that of R-95867, faropenem and oral cephalosporins.
AB  - We compared the in vitro antibacterial activity of DU-6681a against Gram-positive
      and Gram-negative bacteria with that of R-95867, faropenem and oral
      cephalosporins such as cefcapene, cefotiam and cefpodoxime. DU-6681a is an active
      form of the new oral carbapenem compound DZ-2640, which is an ester-type prodrug,
      and R-95867 is an active form of the oral carbapenem CS-834. Against most Gram
      positive bacteria, DU-6681a was as active as or two- to 16-fold more potent than
      R-95867 and faropenem in terms of MIC(90), and comparable to or two- to 64-fold
      more effective than the cephalosporins. Against most Gram-negative bacteria, the
      activity of DU-6681a was the same as or two- to 16-fold more potent than that of
      R-95867, and comparable to or two- to 2048-fold higher than that of faropenem and
      the cephalosporins.

PMID- 10882696
TI  - A novel antibacterial agent derived from the C-terminal domain of streptococcus
      mutans GTP-binding protein.
AB  - A decapeptide, P1, homologous to part of the Streptococcus mutans G-protein (SGP)
      and the Escherichia coli Era protein, was synthesized and examined for growth
      inhibitory effects. When P1 10 mg/L was added to E. coli DH5, the viability of
      the cells was reduced by 13%. Addition of lauric acid enhanced the bactericidal
      effects of P1 (68% killing in the presence of P1 plus lauric acid). Similar
      enhancements were observed for mono lauroyl-rac-glycerol (MLG) and sodium dodecyl
      sulphate (SDS). In cultures treated with both P1 and MLG, there were more
      elongated cells than in cultures treated with detergent or peptide alone. As with
      E. coli, the bactericidal effects of P1 on S. mutans were significantly enhanced
      in the presence of the detergent lauric acid. The combination of the two
      effectors produced >90% killing of S. mutans. Likewise, the combined action of P1
      plus lauric acid reduced the viability of Listeria monocytogenes. P1 did not
      appear to be toxic to human gingival epithelial cells when added at
      concentrations < or = 1000 mg/L. Therefore, P1 has properties which could allow
      it to be used as an antibacterial agent.

PMID- 10882698
TI  - In vitro potency of moxifloxacin, clinafloxacin and sitafloxacin against 248
      genetically defined clinical isolates of Staphylococcus aureus.
AB  - The in vitro potency of three newer fluoroquinolones, moxifloxacin, clinafloxacin
      and sitafloxacin was tested against 248 genetically defined Staphylococcus aureus
      isolates, comprising 116 unrelated S. aureus, seven heterogeneous intermediate
      vancomycin-resistant S. aureus strains as well as 125 clonally related
      methicillin-resistant S. aureus. All strains were susceptible to clinafloxacin
      and sitafloxacin based on an investigational breakpoint of 1 mg/L and were less
      influenced by mutations within the grl and gyr gene loci. In one-quarter to one
      third of the strains tested, reserpine decreased slightly the MICs of
      moxifloxacin, clinafloxacin and sitafloxacin. Compared with moxifloxacin,
      clinafloxacin and sitafloxacin showed a significantly increased anti
      staphylococcal potency.

PMID- 10882699
TI  - In vitro activity of telithromycin (HMR 3647) and seven other antimicrobial
      agents against anaerobic bacteria.
AB  - We assessed the in vitro activity of telithromycin (HMR 3647) and seven other
      antimicrobials against 292 strains of obligately anaerobic bacteria. MICs were
      determined with the microdilution technique and Wilkins-Chalgren broth according
      to DIN 58940-83. MIC50/MIC90s (mg/L) for telithromycin were 4/4 for Bacteroides
      fragilis, Bacteroides ovatus and Bacteroides thetaiotaomicron, 2/4 for
      Fusobacterium spp. and Bilophila wadsworthia, 2/2 for Bacteroides caccae, 1/4 for
      Bacteroides vulgatus, 0.25/4 for Prevotella spp., > or =0.03/0.5 for Clostridium
      spp. and 0.125/4 for Peptostreptococcus spp.

PMID- 10882700
TI  - Resistance of helicobacter pylori to metronidazole, tetracycline and amoxycillin.
AB  - Resistance to metronidazole, tetracycline and amoxycillin, and beta-lactamase
      production were determined for 153 clinical isolates of Helicobacter pylori. Of
      these isolates, 77.8% were resistant to metronidazole (MIC > 8 mg/L), 58.8% to
      tetracycline (MIC > 16 mg/L) and 71.9% to amoxycillin (MIC > 0.5 mg/L); 39.2%
      were multiresistant. Resistance to metronidazole was more common in isolates from
      females than in those from males (P < 0.05). None of the isolates produced beta
      lactamase, so the mechanism of amoxycillin resistance was not linked to
      production of beta-lactamase.

PMID- 10882701
TI  - Susceptibility to quinupristin/dalfopristin and other antibiotics of vancomycin
      resistant enterococci from the UK, 1997 to mid-1999.
AB  - Susceptibility to quinupristin/dalfopristin and other antibiotics was studied for
      clinical isolates of vancomycin-resistant enterococci (VRE) referred by UK
      hospitals between January 1997 and June 1999. Single isolates of VRE from 858
      patients in 136 hospitals were received, of which 76% were Enterococcus faecium
      and 21% were Enterococcus faecalis, the remainder comprising minor species. Most
      isolates were multi-resistant. After allowing for the effect of blood, which
      raised the MICs of quinupristin/dalfopristin four-fold, 98.3% of E. faecalis
      isolates and all the Enterococcus avium, Enterococcus casseliflavus and
      Enterococcus gallinarum appeared resistant to quinupristin/dalfopristin, whereas
      98.8% of the E. faecium isolates and the single Enterococcus raffinosus isolate
      were susceptible.

PMID- 10882702
TI  - Enterococcal glycopeptide resistance at an Italian teaching hospital.
AB  - Two thousand one hundred and thirteen strains of enterococci isolated at Pisa
      General Hospital in 1998 were analysed retrospectively to determine their
      glycopeptide resistance. Of all the microorganisms isolated in this period, 14.7%
      were enterococci (1405 Enterococcus faecalis, 19 Enterococcus faecium, six
      Enterococcus avium and 683 Enterococcus spp.). Two hundred and thirty (10.8%) of
      these enterococci were resistant or demonstrated reduced susceptibility to
      vancomycin and/or teicoplanin. The highest rate of resistance was found in
      outpatient enterococcal strains isolated from the urogenital tract. The frequency
      of enterococcal glycopeptide resistance at Pisa Hospital is higher than that
      reported from other areas of Italy.

PMID- 10882703
TI  - Antibiotic susceptibility and mechanisms of beta-lactam resistance in 1310
      strains of pseudomonas aeruginosa: a French multicentre study (1996).
AB  - A total of 1310 consecutive strains of Pseudomonas aeruginosa were collected in
      11 French hospitals in 1996. The percentages of susceptible isolates measured by
      the agar dilution method were: ticarcillin (53%), piperacillin (69%) (MIC 16
      mg/L), ceftazidime (77%), cefepime (55%), cefpirome (40%), aztreonam (57.5%),
      imipenem (81.5%) (MIC 4 mg/L), amikacin (64.5%) (MIC 8 mg/L) and ciprofloxacin
      (58%) (MIC 1 mg/L). Resistance to beta-lactams was linked to the production of
      transferable beta-lactamases (30%), overproduction of cephalosporinase (29%) and
      to non-enzymic mechanisms (38%).

PMID- 10882704
TI  - In vivo activity of the bis-triazole D0870 against drug-susceptible and drug
      resistant strains of the protozoan parasite Trypanosoma cruzi.
AB  - We report the in vivo activity of the bis-triazole derivative D0870 against a
      variety of strains of Trypanosoma cruzi, the causative agent of Chagas' disease,
      including nitroimidazole/nitrofuran-resistant strains. In both acute and chronic
      murine models of the disease, treatment with D0870 at < or = 10 mg/kg on
      alternate days for a total of 20 doses provided 60-100% protection against death,
      regardless of the drug sensitivity of the infecting strain. In the acute model we
      obtained 70-100% parasitological cure in seven of the nine strains tested,
      including one intermediate and two highly drug-resistant strains. D0870 was able
      to cure 30-45% of animals chronically infected with various strains, including
      those harbouring the Colombiana strain, among which no cures were obtained with
      benznidazole. We also found that the anti-T. cruzi activity of D0870 is largely
      retained even if the hosts are immunosuppressed.

PMID- 10882705
TI  - Local antibiotic guidelines for adult community-acquired pneumonia (CAP): a
      survey of UK hospital practice in 1999.
AB  - We investigated the guidelines in British hospitals for the management of adults
      admitted with community-acquired pneumonia (CAP). A questionnaire was sent to one
      consultant respiratory physician in each of the 263 hospitals in the British
      Thoracic Society (BTS) Directory of Training Posts and Services. Two hundred and
      thirteen (81%) responses were received: 178 (84%) had written CAP guidelines, of
      which 123 (69%) printed copies were received. For non-severe CAP a single
      antibiotic (74% of guidelines-most frequently amoxycillin or ampicillin) was the
      usual recommendation with the combination of a beta-lactam and a macrolide the
      second most frequent (24%). The latter combination was recommended for severe CAP
      in 81% of guidelines. Clostridium difficile-associated diarrhoea had influenced
      guideline recommendations, or was commented on as a concern, in 18% of responses.
      Written guidelines for antibiotic therapy in adults with CAP exist in most
      British hospitals and follow broadly the 1993 BTS guidelines, although
      combination therapy is used not infrequently for non-severe CAP.

PMID- 10882706
TI  - Prevalence of two different genes encoding NorA in 23 clinical strains of
      Staphylococcus aureus.

PMID- 10882707
TI  - The effect of banning avoparcin on VRE carriage in The Netherlands.

PMID- 10882708
TI  - Comparison of the Etest and agar dilution methods for susceptibility testing of
      resistant clinical isolates of Haemophilus influenzae from Saudi Arabia.

PMID- 10882709
TI  - Drug resistance in Salmonella typhi in north India with special reference to
      ciprofloxacin.

PMID- 10882710
TI  - Meropenem pharmacokinetics and pharmacodynamics in patients with ventilator
      associated pneumonia.

PMID- 10882711
TI  - Effect of ketoconazole on plasma concentrations of saquinavir.

PMID- 10882712
TI  - Repair of an interstrand DNA cross-link initiated by ERCC1-XPF
      repair/recombination nuclease.
AB  - Interstrand DNA cross-link damage is a severe challenge to genomic integrity.
      Nucleotide excision repair plays some role in the repair of DNA cross-links
      caused by psoralens and other agents. However, in mammalian cells there is
      evidence that the ERCC1-XPF nuclease has a specialized additional function during
      interstrand DNA cross-link repair, beyond its role in nucleotide excision repair.
      We placed a psoralen monoadduct or interstrand cross-link in a duplex, 4-6 bases
      from a junction with unpaired DNA. ERCC1-XPF endonucleolytically cleaved within
      the duplex on either side of the adduct, on the strand having an unpaired 3'
      tail. Cross-links that were cleaved only on the 5' side were purified and
      reincubated with ERCC1-XPF. A second cleavage was then observed on the 3' side.
      Relevant partially unwound structures near a cross-link may be expected to arise
      frequently, for example at stalled DNA replication forks. The results show that
      the single enzyme ERCC1-XPF can release one arm of a cross-link and suggest a
      novel mechanism for interstrand cross-link repair.

PMID- 10882713
TI  - CD14-dependent lipopolysaccharide-induced beta-defensin-2 expression in human
      tracheobronchial epithelium.
AB  - The induction of host antimicrobial molecules following binding of pathogen
      components to pattern recognition receptors such as CD14 and the Toll-like
      receptors (TLRs) is a key feature of innate immunity. The human airway epithelium
      is an important environmental interface, but LPS recognition pathways have not
      been determined. We hypothesized that LPS would trigger beta-defensin (hBD2) mRNA
      in human tracheobronchial epithelial (hTBE) cells through a CD14-dependent
      mechanism, ultimately activating NF-kappa B. An average 3-fold increase in hBD2
      mRNA occurs 24 h after LPS challenge of hTBE cells. For the first time, we
      demonstrate the presence of CD14 mRNA and cell surface protein in hTBE cells and
      show that CD14 neutralization abolishes LPS induction of hBD2 mRNA. Furthermore,
      we demonstrate TLR mRNA in hTBE cells and NF-kappa B activation following LPS.
      Thus, LPS induction of hBD2 in hTBE cells requires CD14, which may complex with a
      TLR to ultimately activate NF-kappa B.

PMID- 10882714
TI  - Age-dependent defect in vascular endothelial growth factor expression is
      associated with reduced hypoxia-inducible factor 1 activity.
AB  - Previous studies have indicated that advanced age is associated with impaired
      angiogenesis in part because of reduced levels of vascular endothelial growth
      factor (VEGF) expression. To investigate potential mechanisms responsible for
      this age-dependent defect in VEGF expression, aortic smooth muscle cells isolated
      from young rabbits (ages 6-8 months) or old rabbits (ages 4-5 years) were exposed
      to normoxic (21% oxygen) or hypoxic (0.1% oxygen) conditions. Hypoxia-induced
      VEGF expression was significantly lower in old versus young cells. VEGF mRNA
      stability in hypoxic conditions was similar in both young and old cells. However,
      transient transfection with a luciferase reporter gene that was transcriptionally
      regulated by the VEGF promoter revealed a significant defect in VEGF up
      regulation following hypoxia in old versus young cells (a 43 versus 117% increase
      in luciferase activity, p < 0.05); this difference was not seen when a deletion
      construct lacking the hypoxia-inducible 1 (HIF-1) binding site was used.
      Moreover, although HIF-1 alpha-mRNA expression was shown to be similar in young
      and old smooth muscle cells, HIF-1 alpha protein and DNA binding activity were
      significantly reduced in old versus young smooth muscle cells that were exposed
      to hypoxia. We propose that age-dependent reduction in hypoxia-induced VEGF
      expression results from reduced HIF-1 activity and may explain the previously
      described age-dependent impairment of angiogenesis in response to ischemia.

PMID- 10882715
TI  - Stimulation of Ras guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm)
      upon tyrosine phosphorylation by the Cdc42-regulated kinase ACK1.
AB  - Ras-GRF1 is a brain-specific guanine nucleotide exchange factor (GEF) for Ras,
      whose activity is regulated in response to Ca(2+) influx and G protein-coupled
      receptor signals. In addition, Ras-GRF1 acts as a GEF for Rac when tyrosine
      phosphorylated following G protein-coupled receptor stimulation. However, the
      mechanisms underlying the regulation of Ras-GRF1 functions remain incompletely
      understood. We show here that activated ACK1, a nonreceptor tyrosine kinase that
      belongs to the focal adhesion kinase family, causes tyrosine phosphorylation of
      Ras-GRF1. On the other hand, kinase-deficient ACK1 exerted no effect. GEF
      activity of Ras-GRF1 toward Ha-Ras, as defined by in vitro GDP binding and
      release assays, was augmented after tyrosine phosphorylation by ACK1. In
      contrast, GEF activity toward Rac1 remained latent, implying that ACK1 does not
      represent a tyrosine kinase that acts downstream of G protein-coupled receptors.
      Consistent with enhanced Ras-GEF activity, accumulation of the GTP-bound form of
      Ras within the cell was shown through the use of Ras-binding domain pull-down
      assays. Furthermore, Ras-dependent activation of ERK2 by Ras-GRF1 was enhanced
      following co-expression of activated ACK1. These results implicate ACK1 as an
      upstream modulator of Ras-GRF1 and suggest a signaling cascade consisting of
      Cdc42, ACK1, Ras-GRF1, and Ras in neuronal cells.

PMID- 10882716
TI  - Induction of vascular endothelial growth factor in human astrocytes by lead.
      Involvement of a protein kinase C/activator protein-1 complex-dependent and
      hypoxia-inducible factor 1-independent signaling pathway.
AB  - The mechanism(s) underlying lead neurotoxicity are not fully elucidated. cDNA
      expression microarray analysis identified lead-sensitive genes in immortalized
      human fetal astrocytes (SV-FHA). Of the represented genes expressed, vascular
      endothelial growth factor (VEGF) was one of the most sensitive. Lead induced VEGF
      mRNA 3-fold and VEGF protein approximately 2-fold with maximum mRNA induction
      following incubation with 10 micrometer lead acetate for 24 h. Phorbol 12
      myristate 13-acetate (PMA), a potent protein kinase C (PKC) activator, increased
      VEGF mRNA 2-fold and PKC inhibition by GF-109203 completely blocked VEGF
      induction by lead. Expression of dominant-negative PKC-epsilon, but not PKC
      alpha, completely inhibited VEGF mRNA induction by lead. Lead activated the
      transcription factor AP-1 and increased AP-1-dependent luciferase expression >2
      fold. Transfection of cells with a c-jun dominant-negative effectively inhibited
      both AP-1 activation and VEGF mRNA induction by lead. Hypoxia-inducible factor 1
      (HIF-1) activity in SV-FHAs was moderately increased by lead (86%) and PMA (96%).
      Pretreatment with GF-109203 completely inhibited these effects of lead and PMA.
      However, lead did not alter HIF-1-dependent luciferase expression and a HIF
      1alpha dominant-negative had no effects on the induction of VEGF mRNA by lead.
      These findings indicate that lead induces VEGF expression in SV-FHAs via a PKC/AP
      1-dependent and HIF-1-independent signaling pathway.

PMID- 10882717
TI  - Brain S100A5 is a novel calcium-, zinc-, and copper ion-binding protein of the EF
      hand superfamily.
AB  - S100A5 is a novel member of the EF-hand superfamily of calcium-binding proteins
      that is poorly characterized at the protein level. Immunohistochemical analysis
      demonstrates that it is expressed in very restricted regions of the adult brain.
      Here we characterized the human recombinant S100A5, especially its interaction
      with Ca(2+), Zn(2+), and Cu(2+). Flow dialysis revealed that the homodimeric
      S100A5 binds four Ca(2+) ions with strong positive cooperativity and an affinity
      20-100-fold higher than the other S100 proteins studied under identical
      conditions. S100A5 also binds two Zn(2+) ions and four Cu(2+) ions per dimer.
      Cu(2+) binding strongly impairs the binding of Ca(2+); however, none of these
      ions change the alpha-helical-rich secondary structure. After covalent labeling
      of an exposed thiol with 2-(4'-(iodoacetamide)anilino)-naphthalene-6-sulfonic
      acid, binding of Cu(2+), but not of Ca(2+) or Zn(2+), strongly decreased its
      fluorescence. In light of the three-dimensional structure of S100 proteins, our
      data suggest that in each subunit the single Zn(2+) site is located at the
      opposite side of the EF-hands. The two Cu(2+)-binding sites likely share ligands
      of the EF-hands. The potential role of S100A5 in copper homeostasis is discussed.

PMID- 10882718
TI  - Structure and anticoagulant activity of sulfated galactans. Isolation of a unique
      sulfated galactan from the red algae Botryocladia occidentalis and comparison of
      its anticoagulant action with that of sulfated galactans from invertebrates.
AB  - We have characterized the structure of a sulfated d-galactan from the red algae
      Botryocladia occidentalis. The following repeating structure (-4-alpha-d-Galp-1-
      >3-beta-d-Galp-1-->) was found for this polysaccharide, but with a variable
      sulfation pattern. Clearly one-third of the total alpha-units are 2,3-di-O
      sulfated and another one-third are 2-O-sulfated. The algal sulfated d-galactan
      has a potent anticoagulant activity (similar potency as unfractionated heparin)
      due to enhanced inhibition of thrombin and factor Xa by antithrombin and/or
      heparin cofactor II. We also extended the experiments to several sulfated
      polysaccharides from marine invertebrates with simple structures, composed of a
      single repeating structure. A 2-O- or 3-O-sulfated l-galactan (as well as a 2-O
      sulfated l-fucan) has a weak anticoagulant action when compared with the potent
      action of the algal sulfated d-galactan. Possibly, the addition of two sulfate
      esters to a single alpha-galactose residue has an "amplifying effect" on the
      anticoagulant action, which cannot be totally ascribed to the increased charge
      density of the polymer. These results indicate that the wide diversity of
      polysaccharides from marine alga and invertebrates is a useful tool to elucidate
      structure/anticoagulant activity relationships.

PMID- 10882719
TI  - Oxysterol 7 alpha-hydroxylase activity by cholesterol 7 alpha-hydroxylase
      (CYP7A).
AB  - A 7 alpha-hydroxylation is necessary for conversion of both cholesterol and 27
      hydroxycholesterol into bile acids. According to current theories, cholesterol 7
      alpha-hydroxylase (CYP7A) is responsible for the former and oxysterol 7 alpha
      hydroxylase (CYP7B) for the latter reaction. CYP7A is believed to have a very
      high substrate specificity whereas CYP7B is active toward oxysterols,
      dehydroepiandrosterone, and pregnenolone. In the present study, 7 alpha
      hydroxylation of various oxysterols in liver and kidney was investigated.
      Surprisingly, human cholesterol 7 alpha-hydroxylase, CYP7A, expressed as a
      recombinant in Escherichia coli and COS cells, was active toward 20(S)
      hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol. This enzyme
      has previously been thought to be specific for cholesterol and cholestanol. A
      partially purified and reconstituted cholesterol 7 alpha-hydroxylase enzyme
      fraction from pig liver showed 7 alpha-hydroxylase activity toward the same
      oxysterols as metabolized by expressed recombinant human and rat CYP7A. The 7
      alpha-hydroxylase activity toward 20(S)-hydroxycholesterol, 25
      hydroxycholesterol, and 27-hydroxycholesterol in rat liver was significantly
      increased by treatment with cholestyramine, an inducer of CYP7A. From the present
      results it may be concluded that CYP7A is able to function as an oxysterol 7
      alpha-hydroxylase, in addition to the previously known human oxysterol 7 alpha
      hydroxylase, CYP7B. These findings may have implications for oxysterol-mediated
      regulation of gene expression and for pathways of bile acid biosynthesis. A
      possible use of 20(S)-hydroxycholesterol as a marker substrate for CYP7A is
      proposed.

PMID- 10882720
TI  - Coassembly of Trp1 and Trp3 proteins generates diacylglycerol- and Ca2+-sensitive
      cation channels.
AB  - To analyze the functional consequences of coassembly of transient receptor
      potential 1 (Trp1) and Trp3 channel proteins, we characterized membrane
      conductances and divalent cation entry derived by separate overexpression and by
      coexpression of both Trp isoforms. Trp1 expression generated a 1-oleoyl-2-acetyl
      sn-glycerol (OAG)-activated conductance that was detectable only in Ca(2+)-free
      extracellular solution. Trp3 expression gave rise to an OAG-activated conductance
      that was suppressed but clearly detectable at physiological Ca(2+)
      concentrations. Coexpression of both species resulted in a constitutively active,
      OAG-sensitive conductance, which exhibited distinctive cation selectivity and
      high sensitivity to inhibition by intracellular Ca(2+). Trp1-expressing cells
      displayed only modest carbachol-induced Ca(2+) entry and lacked OAG-induced
      Sr(2+) entry, whereas Trp3-expressing cells responded to both agents with a
      substantial divalent cation entry. Coexpression of Trp1 plus Trp3 suppressed
      carbachol-induced Ca(2+) entry compared with Trp3 expression and abolished OAG
      induced Sr(2+) entry signals. We concluded that coassembly of Trp1 and Trp3
      resulted in the formation of oligomeric Trp channels that are subject to
      regulation by phospholipase C and Ca(2+). The distinguished Ca(2+) sensitivity of
      these Trp1/Trp3 hetero-oligomers appeared to limit Trp-mediated Ca(2+) signals
      and may be of importance for negative feedback control of Trp function in
      mammalian cells.

PMID- 10882721
TI  - The generation and characterization of antagonist RNA aptamers to human
      oncostatin M.
AB  - Oncostatin M (OSM) is a multifunctional member of the interleukin-6 cytokine
      family. OSM has been implicated as a powerful proinflammatory mediator and may
      represent a potentially important, novel therapeutic opportunity for treatment of
      established rheumatoid arthritis. To further investigate the role of OSM in
      inflammatory disorders, we have isolated a series of RNA aptamers that bind
      specifically to human OSM. The highest affinity aptamer, designated ADR58, has
      been characterized in a series of in vitro and cell based assays. ADR58 has an
      affinity of 7 nm for human OSM, and it can antagonize OSM binding to the gp130
      receptor and specifically antagonize OSM mediated signaling. The aptamer has been
      truncated in length to 33 bases, all pyrimidine positions are substituted with 2'
      fluorine, and 14 of 18 purine positions have been substituted with 2' O-methyl to
      increase stability toward nucleases. This truncated, modified form of ADR58
      retains complete affinity and functional activity for OSM. This aptamer may be
      used as a tool to further investigate the role of OSM in inflammatory disorders
      and may also have role as a therapeutic agent.

PMID- 10882722
TI  - Differences in hyaluronic acid-mediated functions and signaling in arterial,
      microvessel, and vein-derived human endothelial cells.
AB  - Hyaluronic acid (HA), a nonsulfated glycosaminoglycan, regulates cell adhesion
      and migration. Small HA fragments (3-25 disaccharide units) induce
      neovascularization. We investigated the effect of HA and a HA fragment (10-15
      disaccharide units, F1) on primary human endothelial cells (ECs). Human pulmonary
      ECs (HPAEC) and lung microvessel ECs (HMVEC-L) bound HA (K(d) approximately 1 and
      2.3 nm, respectively) and expressed 17,780 and 16,690 HA binding sites,
      respectively. Both ECs showed HA-mediated cell adhesion; however, HMVEC-L was 1.5
      fold better. Human umbilical vein ECs neither bound HA nor showed HA-mediated
      adhesion. All three ECs expressed CD44 ( approximately 110 kDa). The expression
      of receptor for HA-mediated motility (RHAMM) (approximately 80 kDa) was the
      highest in HMVEC-L, followed by HPAEC and human umbilical vein ECs. RHAMM, not
      CD44, bound HA in all three ECs. F1 was better than HA and stimulated a 2. 5- and
      1.8-fold mitogenic response in HMVEC-L and HPAEC, respectively. Both HA and F1
      induced tyrosine phosphorylation of p125(FAK), paxillin, and p42/44 ERK in HMVEC
      L and HPAEC, which was blocked by an anti-RHAMM antibody. These results
      demonstrate that RHAMM is the functional HA receptor in primary human ECs.
      Heterogeneity exists among primary human ECs of different vascular origins, with
      respect to functional HA receptor expression and function.

PMID- 10882723
TI  - The Brf and TATA-binding protein subunits of the RNA polymerase III transcription
      factor IIIB mediate position-specific integration of the gypsy-like element, Ty3.
AB  - Ty3 integrates into the transcription initiation sites of genes transcribed by
      RNA polymerase III. It is known that transcription factors (TF) IIIB and IIIC are
      important for recruiting Ty3 to its sites of integration upstream of tRNA genes,
      but that RNA polymerase III is not required. In order to investigate the
      respective roles of TFIIIB and TFIIIC, we have developed an in vitro integration
      assay in which Ty3 is targeted to the U6 small nuclear RNA gene, SNR6. Because
      TFIIIB can bind to the TATA box upstream of the U6 gene through contacts mediated
      by TATA-binding protein (TBP), TFIIIC is dispensable for in vitro transcription.
      Thus, this system offers an opportunity to test the role of TFIIIB independent of
      a requirement of TFIIIC. We demonstrate that the recombinant Brf and TBP subunits
      of TFIIIB, which interact over the SNR6 TATA box, direct integration at the SNR6
      transcription initiation site in the absence of detectable TFIIIC or TFIIIB
      subunit B". These findings suggest that the minimal requirements for pol III
      transcription and Ty3 integration are very similar.

PMID- 10882724
TI  - SNAP-25 functional domains in SNARE core complex assembly and glutamate release
      of cerebellar granule cells.
AB  - Synaptosomal associated protein of 25 kDa (SNAP-25) is a member of the SNARE
      protein complex that has been implicated in synaptic vesicle docking and fusion.
      In this report, we have generated SNAP-25 mutants and assayed their functions in
      SNARE complex formation and glutamate release from cultured rat cerebellar
      granule cells. In vitro binding studies show that a deletion mutant lacking the C
      terminal 181-206 amino acid sequence inhibits the formation of the SNARE core
      complex. Additional deletion of an N-terminal 1-31 amino acid sequence abolished
      this inhibitory activity. Adenovirus-mediated gene transfer is used to
      overexpress wild-type and mutant SNAP-25 in cerebellar granule cells. Neurons
      overexpressing the wild-type protein show slight reductions in glutamate release,
      ranging from 10 to 15% in both the developing and mature granule cells. A 30-35%
      inhibition is obtained with the C-terminal deletion mutant, and the inhibitory
      effect is abolished in the N- and C-terminal double deletion mutant. These
      results demonstrate that the SNARE core complex exists in a dynamic and
      reversible state, and the formation of the core complex is necessary for
      neurotransmitter release in neurons.

PMID- 10882725
TI  - CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor
      and JAK2.
AB  - The cytokine-inducible SH2 protein-3 (CIS3/SOCS-3/SSI-3) has been shown to
      inhibit the JAK/STAT pathway and act as a negative regulator of fetal liver
      erythropoiesis. Here, we studied the molecular mechanisms by which CIS3 regulates
      the erythropoietin (EPO) receptor (EPOR) signaling in erythroid progenitors and
      Ba/F3 cells expressing the EPOR (BF-ER). CIS3 binds directly to the EPOR as well
      as JAK2 and inhibits EPO-dependent proliferation and STAT5 activation. We have
      identified the region containing Tyr(401) in the cytoplasmic domain of the EPOR
      as a direct binding site for CIS3. Deletion of the Tyr(401) region of the EPOR
      reduced the inhibitory effect of CIS3, suggesting that binding of CIS3 to the
      EPOR augmented the negative effect of CIS3. Both N- and C-terminal regions
      adjacent to the SH2 domain of CIS3 were necessary for binding to EPOR and JAK2.
      In the N-terminal region of CIS3, the amino acid Gly(45) was critical for binding
      to the EPOR but not to JAK2, while Leu(22) was critical for binding to JAK2. The
      mutation of G45A partially reduced ability of CIS3 to inhibit EPO-dependent
      proliferation and STAT5 activation, while L22D mutant CIS3 was completely unable
      to suppress EPOR signaling. Moreover, overexpression of STAT5, which also binds
      to Tyr(401), reduced the binding of CIS3 to the EPOR, and the inhibitory effect
      of CIS3 against EPO signaling, while it did not affect JAB/SOCS-1/SSI-1. These
      data demonstrate that binding of CIS3 to the EPOR augments the inhibitory effect
      of CIS3. CIS3 binding to both EPOR and JAK2 may explain a specific regulatory
      role of CIS3 in erythropoiesis.

PMID- 10882726
TI  - Heterochromatin protein 1 binds to nucleosomes and DNA in vitro.
AB  - Heterochromatin protein 1 (HP1) is a nonhistone chromosomal protein primarily
      associated with the pericentric heterochromatin and telomeres in Drosophila. The
      molecular mechanism by which HP1 specifically recognizes and binds to chromatin
      is unknown. The purpose of this study was to test whether HP1 can bind directly
      to nucleosomes. HP1 binds nucleosome core particles and naked DNA. HP1-DNA
      complex formation is length-dependent and cooperative but relatively sequence
      independent. We show that histone H4 amino-terminal peptides bind to monomeric
      and dimeric HP1 in vitro. Acetylation of lysine residues had no significant
      effect on in vitro binding. The C-terminal chromo shadow domain of HP1
      specifically binds H4 N-terminal peptide. Neither the chromo domain nor chromo
      shadow domain alone binds DNA; intact native HP1 is required for such
      interactions. Together, these observations suggest that HP1 may serve as a cross
      linker in chromatin, linking nucleosomal DNA and nonhistone protein complexes to
      form higher order chromatin structures.

PMID- 10882727
TI  - Purification, characterization, and cDNA cloning of a novel acidic
      endoglycoceramidase from the jellyfish, Cyanea nozakii.
AB  - Endoglycoceramidase (EC ) is an enzyme capable of cleaving the glycosidic linkage
      between oligosaccharides and ceramides in various glycosphingolipids. We report
      here the purification, characterization, and cDNA cloning of a novel
      endoglycoceramidase from the jellyfish, Cyanea nozakii. The purified enzyme
      showed a single protein band estimated to be 51 kDa on SDS-polyacrylamide gel
      electrophoresis. The enzyme showed a pH optimum of 3.0 and was activated by
      Triton X-100 and Lubrol PX but not by sodium taurodeoxycholate. This enzyme
      preferentially hydrolyzed gangliosides, especially GT1b and GQ1b, whereas neutral
      glycosphingolipids were somewhat resistant to hydrolysis by the enzyme. A full
      length cDNA encoding the enzyme was cloned by 5'- and 3'-rapid amplification of
      cDNA ends using a partial amino acid sequence of the purified enzyme. The open
      reading frame of 1509 nucleotides encoded a polypeptide of 503 amino acids
      including a signal sequence of 25 residues and six potential N-glycosylation
      sites. Interestingly, the Asn-Glu-Pro sequence, which is the putative active site
      of Rhodococcus endoglycoceramidase, was conserved in the deduced amino acid
      sequences. This is the first report of the cloning of an endoglycoceramidase from
      a eukaryote.

PMID- 10882728
TI  - Insights into the rotary catalytic mechanism of F0F1 ATP synthase from the cross
      linking of subunits b and c in the Escherichia coli enzyme.
AB  - The transmembrane sector of the F(0)F(1) rotary ATP synthase is proposed to
      organize with an oligomeric ring of c subunits, which function as a rotor,
      interacting with two b subunits at the periphery of the ring, the b subunits
      functioning as a stator. In this study, cysteines were introduced into the C
      terminal region of subunit c and the N-terminal region of subunit b. Cys of N2C
      subunit b was cross-linked with Cys at positions 74, 75, and 78 of subunit c. In
      each case, a maximum of 50% of the b subunit could be cross-linked to subunit c,
      which suggests that either only one of the two b subunits lie adjacent to the c
      ring or that both b subunits interact with a single subunit c. The results
      support a topological arrangement of these subunits, in which the respective N-
      and C-terminal ends of subunits b and c extend to the periplasmic surface of the
      membrane and cAsp-61 lies at the center of the membrane. The cross-linking of Cys
      between bN2C and cV78C was shown to inhibit ATP-driven proton pumping, as would
      be predicted from a rotary model for ATP synthase function, but unexpectedly,
      cross-linking did not lead to inhibition of ATPase activity. ATP hydrolysis and
      proton pumping are therefore uncoupled in the cross-linked enzyme. The c subunit
      lying adjacent to subunit b was shown to be mobile and to exchange with c
      subunits that initially occupied non-neighboring positions. The movement or
      exchange of subunits at the position adjacent to subunit b was blocked by
      dicyclohexylcarbodiimide. These experiments provide a biochemical verification
      that the oligomeric c-ring can move with respect to the b-stator and provide
      further support for a rotary catalytic mechanism in the ATP synthase.

PMID- 10882729
TI  - Identification and characterization of two members of a novel class of the
      interleukin-1 receptor (IL-1R) family. Delineation of a new class of IL-1R
      related proteins based on signaling.
AB  - Two novel members of the interleukin-1 receptor (IL-1R) family, identified by
      homology searches of human genomic sequence data bases, are described. The genes
      have been named according to their structural features: TIGIRR-1 (three
      immunoglobulin domain-containing IL-1 receptor-related) and TIGIRR-2. TIGIRR-2
      has recently been identified as causing mental retardation when mutated (Carrie,
      A., Jun, L., Bienvenu, T., Vinet, M. C., McDonell, N., Couvert, P., Zemni, R.,
      Cardona, A., Van Buggenhout, G., Frints, S., Hamel, B., Moraine, C., Ropers, H.
      H., Strom, T., Howell, G. R., Whittaker, A., Ross, M. T., Kahn, A., Fryns, J. P.,
      Beldjord, C., Marynen, P., and Chelly, J. (1999) Nat. Genet. 23, 25-31) and
      called IL1RAPL, a name we will also use henceforth. Neither receptor alone was
      able to mediate transcriptional activation of NF-kappaB in response to IL-1alpha,
      IL-1beta, or IL-18. In order to begin to elucidate the function of these and
      other orphan IL-1R family members, we have developed a functional assay utilizing
      a panel of chimeric receptors containing the extracellular and transmembrane
      domains of either type I IL-1R or IL-1R accessory protein (AcP) coupled to the
      cytoplasmic domains of all family members. Coexpression of each IL-1R chimera
      with each AcP chimera and an NF-kappaB-responsive reporter demonstrated that the
      cytoplasmic domains could be classified as IL-1R-like, AcP-like, or neither. Any
      IL-1R-like cytoplasmic domain could cooperate with any AcP-like cytoplasmic
      domain. The TIGIRR-1 and IL1RAPL cytoplasmic domains, however, were unable to
      signal as either IL-1R-like or AcP-like components, suggesting that they function
      as a new class of receptors within this family.

PMID- 10882730
TI  - Myosin V plays an essential role in the thyroid hormone-dependent endocytosis of
      type II iodothyronine 5'-deiodinase.
AB  - In astrocytes, thyroxine modulates type II iodothyronine 5'-deiodinase levels by
      initiating the binding of the endosomes containing the enzyme to microfilaments,
      followed by actin-based endocytosis. Myosin V is a molecular motor thought to
      participate in vesicle trafficking in the brain. In this report, we developed an
      in vitro actin-binding assay to characterize the thyroid hormone-dependent
      binding of endocytotic vesicles to microfilaments. Thyroxine and reverse
      triiodothyronine (EC(50) levels approximately 1 nm) were >100-fold more potent
      than 3,5,3'-triiodothyronine in initiating vesicle binding to actin fibers in
      vitro. Thyroxine-dependent vesicle binding was calcium-, magnesium-, and ATP
      dependent, suggesting the participation of one or more myosin motors, presumably
      myosin V. Addition of the myosin V globular tail, lacking the actin-binding head,
      specifically blocked thyroid hormone-dependent vesicle binding, and direct
      binding of the myosin V tail to enzyme-containing endosomes was thyroxine
      dependent. Progressive NH(2)-terminal deletion of the myosin V tail and domain
      specific antibody inhibition studies revealed that the thyroxine-dependent
      vesicle-tethering domain was localized to the last 21 amino acids of the COOH
      terminus. These data show that myosin V is responsible for thyroid hormone
      dependent binding of primary endosomes to the microfilaments and suggest that
      this motor mediates the actin-based endocytosis of the type II iodothyronine
      deiodinase.

PMID- 10882731
TI  - Yeast lacking superoxide dismutase(s) show elevated levels of "free iron" as
      measured by whole cell electron paramagnetic resonance.
AB  - A current hypothesis explaining the toxicity of superoxide anion in vivo is that
      it oxidizes exposed [4Fe-4S] clusters in certain vulnerable enzymes causing
      release of iron and enzyme inactivation. The resulting increased levels of "free
      iron" catalyze deleterious oxidative reactions in the cell. In this study, we
      used low temperature Fe(III) electron paramagnetic resonance (EPR) spectroscopy
      to monitor iron status in whole cells of the unicellular eukaryote, Saccharomyces
      cerevisiae. The experimental protocol involved treatment of the cells with
      desferrioxamine, a cell-permeant, Fe(III)-specific chelator, to promote oxidation
      of all of the "free iron" to the Fe(III) state wherein it is EPR-detectable.
      Using this method, a small amount of EPR-detectable iron was detected in the wild
      type strain, whereas significantly elevated levels were found in strains lacking
      CuZn-superoxide dismutase (CuZn-SOD) (sod1 delta), Mn-SOD (sod2 delta), or both
      SODs, throughout their growth but particularly in stationary phase. The
      accumulation was suppressed by expression of wild-type human CuZn-SOD (in the
      sod1 delta mutant), by pmr1, a genetic suppressor of the sod delta mutant
      phenotype (in the sod1 delta sod2 delta double knockout strain), and by anaerobic
      growth. In wild-type cells, an increase in the EPR-detectable iron pool could be
      induced by treatment with paraquat, a redox-cycling drug that generates
      superoxide. Cells that were not pretreated with desferrioxamine had Fe(III) EPR
      signals that were equally as strong as those from treated cells, indicating that
      "free iron" accumulated in the ferric form in our strains in vivo. Our results
      indicate a relationship between superoxide stress and iron handling and support
      the above hypothesis for superoxide-related oxidative damage.

PMID- 10882732
TI  - The replacement of ATP by the competitive inhibitor emodin induces conformational
      modifications in the catalytic site of protein kinase CK2.
AB  - The structure of a complex between the catalytic subunit of Zea mays CK2 and the
      nucleotide binding site-directed inhibitor emodin (3-methyl-1,6,8
      trihydroxyanthraquinone) was solved at 2.6-A resolution. Emodin enters the
      nucleotide binding site of the enzyme, filling a hydrophobic pocket between the N
      terminal and the C-terminal lobes, in the proximity of the site occupied by the
      base rings of the natural co-substrates. The interactions between the inhibitor
      and CK2 alpha are mainly hydrophobic. Although the C-terminal domain of the
      enzyme is essentially identical to the ATP-bound form, the beta-sheet in the N
      terminal domain is altered by the presence of emodin. The structural data
      presented here highlight the flexibility of the kinase domain structure and
      provide information for the design of selective ATP competitive inhibitors of
      protein kinase CK2.

PMID- 10882733
TI  - Polyomavirus enhancer-binding protein 2/core binding factor/acute myeloid
      leukemia factors contribute to the cell type-specific activity of the CD11a
      integrin gene promoter.
AB  - The CD11a/CD18 leukocyte integrin (LFA-1; also known as alphaL/beta2) mediates
      leukocyte transendothelial migration during immune and inflammatory responses and
      participates in lymphoma metastasis. CD11a/CD18 leukocyte-restricted expression
      is controlled by the CD11a gene promoter, which confers tissue-specific
      expression to reporter genes in vitro and in vivo. DNase I protection analysis of
      the CD11a proximal gene promoter revealed DNA-protein interactions centered at
      position -110 (CD11a-110). Disruption of CD11a-110 reduced CD11a promoter
      activity in a cell type-specific manner, as it reduced its activity by 70% in
      Jurkat lymphoid cells, whereas the effect was considerably lower in K562 and
      HepG2 cells. Electrophoretic mobility shift assays showed evidence of cell type
      specific differences in CD11a-110 binding and indicated its specific recognition
      by members of the polyomavirus enhancer-binding protein 2/core binding factor
      (CBF)/acute myeloid leukemia (AML) family of transcription factors. AML1B/CBFbeta
      transactivated the CD11a promoter, with AML1B/CBFbeta-mediated transactivation
      being completely dependent on the integrity of the CD11a-110 element. Therefore,
      CBF/AML factors play a role in the cell type-restricted transcription of the
      CD11a integrin gene through recognition of CD11a-110. The involvement of CBF/AML
      factors in CD11a expression raises the possibility that CD11a/CD18 expression
      might be deregulated in acute myeloid and B-lineage acute lymphoblastic
      leukemias, thus contributing to their altered adhesion and metastatic potential.

PMID- 10882734
TI  - Glycosylation of the hepatitis C virus envelope protein E1 is dependent on the
      presence of a downstream sequence on the viral polyprotein.
AB  - The addition of N-linked oligosaccharides to Asn-X-(Ser/Thr) sites is catalyzed
      by the oligosaccharyltransferase, an enzyme closely associated with the
      translocon and generally thought to have access only to nascent chains as they
      emerge from the ribosome. However, the presence of the sequon does not
      automatically ensure core glycosylation because many proteins contain sequons
      that remain either nonglycosylated or glycosylated to a variable extent. In this
      study, hepatitis C virus (HCV) envelope protein E1 was used as a model to study
      the efficiency of N-glycosylation. HCV envelope proteins, E1 and E2, were
      released from a polyprotein precursor after cleavage by host signal peptidase(s).
      When expressed alone, E1 was not efficiently glycosylated. However, E1
      glycosylation was improved when expressed as a polyprotein including full-length
      or truncated forms of E2. These data indicate that glycosylation of E1 is
      dependent on the presence of polypeptide sequences located downstream of E1 on
      HCV polyprotein.

PMID- 10882735
TI  - Reconstitution of ATP- and cytosol-dependent transport of de novo synthesized
      ceramide to the site of sphingomyelin synthesis in semi-intact cells.
AB  - Transport of ceramide synthesized at the endoplasmic reticulum to the Golgi
      compartment, where sphingomyelin (SM) synthase exists, was reconstituted within
      semi-intact Chinese hamster ovary cells. When [(3)H]ceramide that had been
      produced from [(3)H]sphingosine at 15 degrees C in perforated cells was chased at
      37 degrees C, [(3)H]ceramide-to-[(3)H]SM conversion occurred in a cytosol
      dependent manner. In various aspects (i.e. kinetics, ATP dependence, and
      temperature dependence), [(3)H]ceramide-to-[(3)H]SM conversion in perforated
      cells was consistent with that in intact cells. The cytosol from LY-A strain, a
      Chinese hamster ovary cell mutant defective in endoplasmic reticulum-to-Golgi
      transport of ceramide, did not support [(3)H]ceramide-to-[(3)H]SM conversion in
      perforated wild-type cells, whereas the wild-type cytosol rescued the conversion
      in perforated LY-A cells. Brefeldin A-treated cells, in which the endoplasmic
      reticulum and the Golgi apparatus were merged, no longer required cytosol for
      conversion of [(3)H]ceramide to [(3)H]SM. These results indicated that the assay
      of [(3)H]ceramide-to-[(3)H]SM conversion in semi-intact cells is a faithful in
      vitro assay for the activity of cytosol-dependent transport of ceramide and that
      LY-A cells are defective in a cytosolic factor involved in ceramide transport. In
      addition, conversion of [(3)H]ceramide to [(3)H]glucosylceramide in semi-intact
      cells was little dependent on cytosol, suggesting that ceramide reached the site
      of glucosylceramide synthesis by a cytosol-independent (or less dependent)
      pathway.

PMID- 10882736
TI  - Visualization of the calcitonin receptor-like receptor and its receptor activity
      modifying proteins during internalization and recycling.
AB  - Expression of the calcitonin receptor-like receptor (CRLR) and its receptor
      activity modifying proteins (RAMPs) can produce calcitonin gene-related peptide
      (CGRP) receptors (CRLR/RAMP1) and adrenomedullin (AM) receptors (CRLR/RAMP2 or 
      3). A chimera of the CRLR and green fluorescent protein (CRLR-GFP) was used to
      study receptor localization and trafficking in stably transduced HEK 293 cells,
      with or without co-transfection of RAMPs. CRLR-GFP failed to generate responses
      to CGRP or AM without RAMPs. Furthermore, CRLR-GFP was not found in the plasma
      membrane and its localization was unchanged after agonist exposure. When stably
      coexpressed with RAMPs, CRLR-GFP appeared on the cell surface and was fully
      active in intracellular cAMP production and calcium mobilization. Agonist
      mediated internalization of CRLR-GFP was observed in RAMP1/CGRP or AM, RAMP2/AM,
      and RAMP3/AM, which occurred with similar kinetics, indicating the existence of
      ligand-specific regulation of CRLR internalization by RAMPs. This internalization
      was strongly inhibited by hypertonic medium (0.45 m sucrose) and paralleled
      localization of rhodamine-labeled transferrin, suggesting that CRLR endocytosis
      occurred predominantly through a clathrin-dependent pathway. A significant
      proportion of CRLR was targeted to lysosomes upon binding of the ligands, and
      recycling of the internalized CRLR was not efficient. In HEK 293 cells stably
      expressing CRLR-GFP and Myc-RAMPs, these rhodamine-labeled RAMPs were co
      localized with CRLR-GFP in the presence and absence of the ligands. Thus, the
      CRLR is endocytosed together with RAMPs via clathrin-coated vesicles, and both
      the internalized molecules are targeted to the degradative pathway.

PMID- 10882737
TI  - Influence of HMG-1 and adenovirus oncoprotein E1A on early stages of
      transcriptional preinitiation complex assembly.
AB  - The TATA-binding protein (TBP) in the TFIID complex binds specifically to the
      TATA-box to initiate the stepwise assembly of the preinitiation complex (PIC) for
      RNA polymerase II transcription. Transcriptional activators and repressors
      compete with general transcription factors at each step to influence the course
      of the assembly. To investigate this process, the TBP.TATA complex was titrated
      with HMG-1 and the interaction monitored by electrophoretic mobility shift
      assays. The titration produced a ternary HMG-1.TBP. TATA complex, which exhibits
      increased mobility relative to the TBP. TATA complex. The addition of increasing
      levels of TFIIB to this complex results in the formation of the TFIIB.TBP.TATA
      complex. However, in the reverse titration, with very high mole ratios of HMG-1
      present, TFIIB is not dissociated off and a complex is formed that contains all
      factors. The simultaneous addition of E1A to a mixture of TBP and TATA; or HMG-1,
      TBP, and TATA; or TFIIB, TBP, and TATA inhibits complex formation. On the other
      hand, E1A added to the pre-established complexes shows a significantly reduced
      capability to disrupt the complex. In add-back experiments with all complexes,
      increased levels of TBP re-established the complexes, indicating that the primary
      target for E1A in all complexes is TBP.

PMID- 10882738
TI  - Mechanism of I kappa B alpha binding to NF-kappa B dimers.
AB  - X-ray crystal structures of the NF-kappa B.I kappa B alpha complex revealed an
      extensive and complex protein-protein interface involving independent structural
      elements present in both I kappa B alpha and NF-kappa B. In this study, we employ
      a gel electrophoretic mobility shift assay to assess and quantitate the relative
      contributions of the observed interactions toward overall complex binding
      affinity. I kappa B alpha preferentially binds to the p50/p65 heterodimer and p65
      homodimer, with binding to p50 homodimer being significantly weaker. Our results
      indicate that the nuclear localization sequence and the region C-terminal to it
      of the NF-kappa B p65 subunit is a major contributor to NF-kappa B. I kappa B
      alpha complex formation. Additionally, there are no contacts between the
      corresponding nuclear localization signal tetrapeptide of p50 and I kappa B
      alpha. A second set of interactions involving the acidic C-terminal/PEST-like
      region of I kappa B alpha and the NF-kappa B p65 subunit N-terminal domain also
      contributes binding energy toward formation of the complex. This interaction is
      highly dynamic and nonspecific in nature, as shown by oxidative cysteine cross
      linking. Phosphorylation of the C-terminal/PEST-like region by casein kinase II
      further enhances binding.

PMID- 10882739
TI  - Structural characterization of the cysteine-rich domain of TFIIH p44 subunit.
AB  - In an effort to understand the structure function relationship of TFIIH, a
      transcription/repair factor, we focused our attention on the p44 subunit, which
      plays a central role in both mechanisms. The amino-terminal portion of p44 has
      been shown to be involved in the regulation of the XPD helicase activity; here we
      show that its carboxyl-terminal domain is essential for TFIIH transcription
      activity and that it binds three zinc atoms through two independent modules. The
      first contains a C4 zinc finger motif, whereas the second is characterized by a
      CX(2)CX(2-4)FCADCD motif, corresponding to interleaved zinc binding sites. The
      solution structure of this second module reveals an unexpected homology with the
      regulatory domain of protein kinase C and provides a framework to study its role
      at the molecular level.

PMID- 10882741
TI  - Identification, cloning, expression, and biochemical characterization of the
      testis-specific RNA polymerase II elongation factor ELL3.
AB  - The human ELL gene, which is a frequent target for translocation in acute myeloid
      leukemia, was initially isolated from rat liver nuclei and found to be an RNA
      polymerase II elongation factor. Based on homology to ELL, we later cloned ELL2
      and demonstrated that it can also increase the catalytic rate of transcription
      elongation by RNA polymerase II. To better understand the role of ELL proteins in
      the regulation of transcription by RNA polymerase II, we have initiated a search
      for proteins related to ELLs. In this report, we describe the molecular cloning,
      expression, and characterization of ELL3, a novel RNA polymerase II elongation
      factor approximately 50% similar to both ELL and ELL2. Our transcriptional
      studies have demonstrated that ELL3 can also increase the catalytic rate of
      transcription elongation by RNA polymerase II. The C-terminal domain of ELL,
      which we recently demonstrated to be required and sufficient for the
      immortalization of myeloid progenitor cells, shares strong similarities to the C
      terminal domain of ELL3. ELL3 was localized by immunofluorescence to the nucleus
      of cells, and Northern analysis indicated that ELL3 is a testis-specific RNA
      polymerase II elongation factor.

PMID- 10882740
TI  - Phosphorylation of the vasodilator-stimulated phosphoprotein regulates its
      interaction with actin.
AB  - The vasodilator-stimulated phosphoprotein (VASP) is a major substrate for cyclic
      nucleotide-dependent kinases in platelets and other cardiovascular cells. It
      promotes actin nucleation and binds to actin filaments in vitro and associates
      with stress fibers in cells. The VASP-actin interaction is salt-sensitive,
      arguing for electrostatic interactions. Hence, phosphorylation may significantly
      alter the actin binding properties of VASP. This hypothesis was investigated by
      analyzing complex formation of recombinant murine VASP with actin after
      phosphorylation with cAMP-dependent kinase in different assays. cAMP-dependent
      kinase phosphorylation had a negative effect on both actin nucleation and VASP
      interaction with actin filaments, with the actin nucleating capacity being more
      affected than actin filament binding and bundling. Replacing VASP residues known
      to be phosphorylated in vivo by acidic residues to mimic phosphorylation had
      similar although less dramatic effects on VASP-actin interactions. In contrast,
      phosphorylation had no significant effect on VASP oligomerization or its
      interaction with its known ligands profilin, vinculin, and zyxin. When
      overexpressing VASP mutants in eukaryotic cells, they all showed targeting to
      focal contacts and stress fibers. Our results imply that VASP phosphorylation may
      act as an immediate negative regulator of actin dynamics.

PMID- 10882742
TI  - Chopper, a new death domain of the p75 neurotrophin receptor that mediates rapid
      neuronal cell death.
AB  - The cytoplasmic juxtamembrane region of the p75 neurotrophin receptor (p75(NTR))
      has been found to be necessary and sufficient to initiate neural cell death. The
      region was named "Chopper" to distinguish it from CD95-like death domains. A 29
      amino acid peptide corresponding to the Chopper region induced caspase- and
      calpain-mediated death in a variety of neural and non-neural cell types and was
      not inhibited by signaling through Trk (unlike killing by full-length p75(NTR)).
      Chopper triggered cell death only when bound to the plasma membrane by a lipid
      anchor, whereas non-anchored Chopper acted in a dominant-negative manner,
      blocking p75(NTR)-mediated death both in vitro and in vivo. Removal of the
      ectodomain of p75(NTR) increased the potency of Chopper activity, suggesting that
      it regulates the association of Chopper with downstream signaling proteins.

PMID- 10882743
TI  - High affinity binding between lipoprotein lipase and lipoproteins involves
      multiple ionic and hydrophobic interactions, does not require enzyme activity,
      and is modulated by glycosaminoglycans.
AB  - Lipoprotein lipase (LPL) physically associates with lipoproteins and hydrolyzes
      triglycerides. To characterize the binding of LPL to lipoproteins, we studied the
      binding of low density lipoproteins (LDL), apolipoprotein (apo) B17, and various
      apoB-FLAG (DYKDDDDK octapeptide) chimeras to purified LPL. LDL bound to LPL with
      high affinity (K(d) values of 10(-12) m) similar to that observed for the binding
      of LDL to its receptors and 1D1, a monoclonal antibody to LDL, and was greater
      than its affinity for microsomal triglyceride transfer protein. LDL-LPL binding
      was sensitive to both salt and detergents, indicating the involvement of both
      hydrophobic and hydrophilic interactions. In contrast, the N-terminal 17% of apoB
      interacted with LPL mainly via ionic interactions. Binding of various apoB fusion
      peptides suggested that LPL bound to apoB at multiple sites within apoB17.
      Tetrahydrolipstatin, a potent enzyme activity inhibitor, had no effect on apoB
      LPL binding, indicating that the enzyme activity was not required for apoB
      binding. LDL-LPL binding was inhibited by monoclonal antibodies that recognize
      amino acids 380-410 in the C-terminal region of LPL, a region also shown to
      interact with heparin and LDL receptor-related protein. The LDL-LPL binding was
      also inhibited by glycosaminoglycans (GAGs); heparin inhibited the interactions
      by approximately 50% and removal of trace amounts of heparin from LPL
      preparations increased LDL binding. Thus, we conclude that the high affinity
      binding between LPL and lipoproteins involves multiple ionic and hydrophobic
      interactions, does not require enzyme activity and is modulated by GAGs. It is
      proposed that LPL contains a surface exposed positively charged amino acid
      cluster that may be important for various physiological interactions of LPL with
      different biologically important molecules. Moreover, we postulate that by
      binding to this cluster, GAGs modulate the association between LDL and LPL and
      the in vivo metabolism of LPL.

PMID- 10882744
TI  - P-selectin glycoprotein ligand-1 and E-selectin ligand-1 are differentially
      modified by fucosyltransferases Fuc-TIV and Fuc-TVII in mouse neutrophils.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1) and E-selectin ligand-1 (ESL-1) are the
      two major selectin ligands on mouse neutrophils. Transfection experiments
      demonstrate that each ligand requires alpha1,3-fucosylation for selectin-binding.
      However, the relative contributions made by the two known myeloid alpha1, 3
      fucosyltransferases Fuc-TVII or Fuc-TIV to this alpha1, 3-fucosylation are not
      yet clear. To address this issue, we have used mice deficient in Fuc-TIV and/or
      Fuc-TVII to examine how these enzymes generate selectin-binding glycoforms of
      PSGL-1 and ESL-1 in mouse neutrophils. Selectin binding was analyzed by affinity
      isolation experiments using recombinant, antibody-like forms of the respective
      endothelial selectins. We observe essentially normal binding of E- or P-selectin
      to PSGL-1 expressed by Fuc-TIV-deficient neutrophils but find that PSGL-1
      expressed by Fuc-TVII-deficient neutrophils is not bound by E- or P-selectin. By
      contrast, E-selectin binds with normal efficiency to ESL-1 on Fuc-TVII-deficient
      neutrophils but exhibits an 80% reduction in its ability to bind ESL-1 isolated
      from Fuc-TIV-deficient neutrophils. The same specificity with which Fuc-TVII and
      Fuc-TIV generate selectin-binding forms of PSGL-1 and ESL-1 was found in
      transfection experiments with CHO-Pro(-)5 cells. In contrast, each
      fucosyltransferase alone could generate selectin-binding glycoforms of each of
      the two ligands in CHO-DUKX-B1 cells. Our data imply that in mouse neutrophils
      and their precursors, Fuc-TVII exclusively directs expression of PSGL-1
      glycoforms bound with high affinity by P-selectin. By contrast, Fuc-TIV
      preferentially directs expression of ESL-1 glycoforms that exhibit high affinity
      for E-selectin. This substrate specificity can be mimicked in CHO-Pro(-)5 cells.

PMID- 10882745
TI  - Functional consequences of mutations in the smooth muscle myosin heavy chain at
      sites implicated in familial hypertrophic cardiomyopathy.
AB  - Familial hypertrophic cardiomyopathy (FHC) is frequently associated with
      mutations in the beta-cardiac myosin heavy chain. Many of the implicated residues
      are located in highly conserved regions of the myosin II class, suggesting that
      these mutations may impair the basic functions of the molecular motor. To test
      this hypothesis, we have prepared recombinant smooth muscle heavy meromyosin with
      mutations at sites homologous to those associated with FHC by using a
      baculovirus/insect cell expression system. Several of the heavy meromyosin
      mutants, in particular R403Q, showed an increase in actin filament velocity in a
      motility assay and an enhanced actin-activated ATPase activity. Single molecule
      mechanics, using a laser trap, gave unitary displacements and forces for the
      mutants that were similar to wild type, but the attachment times to actin
      following a unitary displacement were markedly reduced. These results suggest
      that the increases in activity are due to a change in kinetics and not due to a
      change in the intrinsic mechanical properties of the motor. In contrast to
      earlier reports, we find that mutations in residues implicated in FHC affect
      motor function by enhancing myosin activity rather than by a loss of function.

PMID- 10882746
TI  - Generation and novel distribution of matrix metalloproteinase-derived aggrecan
      fragments in porcine cartilage explants.
AB  - We have studied aggrecan catabolism mediated by matrix metalloproteinases (MMPs)
      in a porcine cartilage culture system. Using antibodies specific for DIPEN(341)
      and (342)FFGVG neoepitopes, we have detected MMP-derived fragments in conditioned
      medium and cultured cartilage, by radioimmunoassay, Western blotting, and
      immunolocalization. Radioimmunoassay revealed that the amount (pmol of epitope/mg
      of total glycosaminoglycan) of (342)FFGVG epitope released from cartilage
      remained constant over a 5-day culture period and was not increased by IL-1alpha
      or retinoate. However, the proportion (pmol of epitope/mg of released
      glycosaminoglycan) of (342)FFGVG epitope released was decreased upon stimulation,
      consistent with the involvement of a non-MMP proteinase, such as aggrecanase. The
      data suggest that in vitro MMPs may be involved in the base-line catabolism of
      aggrecan. Immunolocalization experiments showed that DIPEN(341) and ITEGE(373)
      epitopes were increased by treatment with IL-1alpha and retinoate. Confocal
      microscopy revealed that ITEGE(373) epitope was largely intracellular but with
      matrix staining in the superficial zone, whereas DIPEN(341) epitope was cell
      associated and widely distributed in the matrix. Surprisingly, the majority of
      (342)FFGVG epitope, determined by radioimmunoassay and Western blotting, was
      retained in the tissue despite the absence of a G1 domain anchor. Interleukin
      1alpha stimulation caused a marked increase in tissue DIPEN(341) and (342)FFGVG
      epitope, and the (342)FFGVG fragments retained in the tissue were larger than
      those released into the medium. Active porcine aggrecanase was unable to cleave
      (342)FFGVG fragments at the downward arrowGlu(373) downward arrowAla(374) bond
      but cleaved intact aggrecan at this site, suggesting that (342)FFGVG fragments
      are not substrates for aggrecanase. The apparent retention of large (342)FFGVG
      fragments within cartilage, and their resistance to N-terminal cleavage by
      aggrecanase suggests that (342)FF6V6 fragments may have a role in cartilage
      homeostasis.

PMID- 10882748
TI  - Interleukin-15 induces rapid tyrosine phosphorylation of STAT6 and the expression
      of interleukin-4 in mouse mast cells.
AB  - Interleukin (IL)-4 plays an important role in the differentiation of naive T
      helper (Th) cells into Th2. Mast cells can produce a significant amount of IL-4
      and have been proposed to play a major role in the induction of Th2 responses.
      Recently, it has been reported that mast cells have a distinct IL-15 receptor
      system different from that of T or natural killer cells. In the present study, we
      demonstrated that IL-15 induced IL-4 production from a mouse mast cell line,
      MC/9, and bone marrow-derived mast cells. IL-4 mRNA expression was increased by
      IL-15, suggesting that IL-15 promotes IL-4 expression at the transcriptional
      level. In these mast cells, signal transducer and activator of transcription
      (STAT) 6 were rapidly tyrosine-phosphorylated in response to IL-15. In MC/9
      cells, the expression of a C-terminally truncated dominant negative form of STAT6
      significantly suppressed the IL-4 mRNA up-regulation by IL-15, suggesting that
      STAT6 activation is essential for the IL-15-mediated IL-4 production.
      Additionally, tyrosine phosphorylation of Tyk2 was rapidly increased by IL-15
      treatment in this cell line. Altogether, our results suggest that IL-15 plays an
      important role in stimulating early IL-4 production in mast cells that may be
      responsible for the initiation of Th2 response.

PMID- 10882749
TI  - The genetics of childhood cataract.
AB  - Human congenital cataract has a diverse aetiology. In the proportion of cases
      where the cause is genetic, the disease shows wide phenotypic and genetic
      heterogeneity. Over the past few years, much research has been devoted to mapping
      the genes that underlie the disorder. This has been helped by the extensive array
      of naturally occurring and genetically engineered mouse cataract models and the
      abundance of human candidate genes. Most progress to date has been in the
      identification of genetic mutations causing autosomal dominant congenital
      cataract where eight genes have been implicated in cataractogenesis. Overall
      there is good correlation between the genetic mutations so far identified and the
      resulting lens phenotype but it is clear that mutations at more that one locus
      may give rise to similar forms of cataract. The identification of genes causing
      inherited forms of cataract will improve our understanding of the mechanisms
      underlying cataractogenesis in childhood and provide further insights into normal
      lens development and physiology. Perhaps more importantly, it is likely that some
      of the genes causing early onset cataract will be implicated in age related
      cataract which remains the commonest cause of blindness in the world.

PMID- 10882751
TI  - The ACE I allele is associated with increased risk for ruptured intracranial
      aneurysms.
AB  - Genetic and environmental factors play roles in the aetiology of ruptured
      intracranial aneurysms. Hypertension has been reported as a risk factor for
      intracranial aneurysm haemorrhage. We have tested if genotypes at the angiotensin
      converting enzyme (ACE) gene locus are associated with ruptured intracranial
      aneurysms. The insertion/deletion polymorphism in the ACE gene was genotyped in
      258 subjects presenting in East Anglia with ruptured intracranial aneurysms
      (confirmed at surgery or angiographically) and 299 controls from the same region.
      ACE allele frequencies were significantly different in the cases and the controls
      (alleles chi(2)(1)=4.67, p=0.03). The I allele was associated with aneurysm risk
      (odds ratio for I allele v D allele = 1.3 (95% CI=1.02-1-65); odds ratio for II v
      DD genotype = 1.67 (95% CI=1.04-2.66)). The I allele at the ACE locus is over
      represented in subjects with ruptured intracranial aneurysms. These data are
      supported by non-significant trends in the same direction in two previous smaller
      studies. Thus, this allele may be associated with risk for ruptured intracranial
      aneurysms.

PMID- 10882750
TI  - A clinical study of 57 children with fetal anticonvulsant syndromes.
AB  - BACKGROUND: Anticonvulsants taken in pregnancy are associated with an increased
      risk of malformations and developmental delay in the children. To evaluate the
      pattern of abnormalities associated with prenatal anticonvulsant exposure
      further, we undertook a clinical study of 57 children with fetal anticonvulsant
      syndromes. METHODS: Fifty two children were ascertained through the Fetal
      Anticonvulsant Syndrome Association and five were referred to the Aberdeen
      Medical Genetics Service. Pregnancy and medical history were obtained through a
      standardised questionnaire and interview and the children were examined. RESULTS:
      Thirty four (60%) were exposed in utero to valproate alone, four (7%) to
      carbamazepine alone, four (7%) to phenytoin alone, and 15 (26%) to more than one
      anticonvulsant. Forty six (81%) reported behavioural problems, 22 (39%) with
      hyperactivity or poor concentration of whom four (7%) had a diagnosis of
      attention deficit and hyperactivity disorder. Thirty four (60%) reported two or
      more autistic features, of whom four had a diagnosis of autism and two of
      Asperger's syndrome. Forty four (77%) had learning difficulties, 46 (81%) had
      speech delay, 34 (60%) had gross motor delay, and 24 (42%) had fine motor delay.
      Nineteen (33%) had glue ear and 40 (70%) had joint laxity involving all sizes of
      joints. Of 46 who had formal ophthalmic evaluation, 16 (34%) had myopia.
      CONCLUSIONS: Speech delay, joint laxity, glue ear, and myopia are common in the
      fetal anticonvulsant syndromes and autistic features and hyperactivity form part
      of the behavioural phenotype.

PMID- 10882753
TI  - Complementation studies in the cblA class of inborn error of cobalamin
      metabolism: evidence for interallelic complementation and for a new
      complementation class (cblH).
AB  - AIM: To investigate genetic heterogeneity within the cblA class of inborn error
      of cobalamin metabolism. CONTEXT: The cblA disorder is characterised by vitamin
      B12 (cobalamin) responsive methylmalonic aciduria and deficient synthesis of
      adenosylcobalamin, required for activity of the mitochondrial enzyme
      methylmalonyl CoA mutase. The cblA gene has not been identified or cloned. We
      have previously described a patient with the clinical and biochemical phenotype
      of the cblA disorder whose fibroblasts complemented cells from patients with all
      known types of inborn error of adenosylcobalamin synthesis, including cblA.
      METHODS: We have performed somatic cell complementation analysis of the cblA
      variant fibroblast line with a panel of 28 cblA lines. We have also performed
      detailed complementation analysis on a panel of 10 cblA fibroblast lines, not
      including the cblA variant line. RESULTS: The cblA variant line complemented all
      28 cell lines of the panel. There was evidence for interallelic complementation
      among the 10 cblA lines used for detailed complementation analysis; no cell line
      in this panel complemented all other members. CONCLUSIONS: These results strongly
      suggest that the cblA variant represents a novel complementation class, which we
      have designated cblH and which represents a mutation at a distinct gene. They
      also suggest that the cblA gene encodes a protein that functions as a multimer,
      allowing for extensive interallelic complementation.

PMID- 10882752
TI  - Gene amplification in PNETs/medulloblastomas: mapping of a novel amplified gene
      within the MYCN amplicon.
AB  - OBJECTIVES: The pathological entity of primitive neuroectodermal
      tumour/medulloblastoma (PNET/MB) comprises a very heterogeneous group of
      neoplasms on a clinical as well as on a molecular level. We evaluated the
      importance of DNA amplification in medulloblastomas and other primitive
      neuroectodermal tumours (PNETs) of the CNS. METHOD: Restriction landmark genomic
      scanning (RLGS), a method that allows the detection of low level amplification,
      was used. RLGS provides direct access to DNA sequences circumventing positional
      cloning efforts. Furthermore, we analysed several samples by CGH. DESIGN: Twenty
      primary medulloblastomas, five supratentorial PNETs, and five medulloblastoma
      cell lines were studied. RESULTS: Although our analysis confirms that gene
      amplification is generally a rare event in childhood PNET/MB, we found a total of
      17 DNA fragments that were amplified in seven different tumours. Cloning and
      sequencing of several of these fragments confirmed the previous finding of MYC
      amplification in the cell line D341 Med and identified novel DNA sequences
      amplified in PNET/MB. We describe for the first time amplification of the novel
      gene, NAG, in a subset of PNET/MB. Despite genomic amplification, NAG was not
      overexpressed in the tumours studied. We have determined that NAG maps less than
      50 kb 5' of DDX1 and approximately 400 kb telomeric of MYCN on chromosome 2p24.
      CONCLUSION: We found a similar but slightly higher frequency of amplification
      than previously reported. We present several DNA fragments that may belong to the
      CpG islands of novel genes amplified in a small subset of PNET/MB. As an example
      we describe for the first time the amplification of NAG in the MYCN amplicon in
      PNET/MB.

PMID- 10882755
TI  - Genitopatellar syndrome: a new condition comprising absent patellae, scrotal
      hypoplasia, renal anomalies, facial dysmorphism, and mental retardation.
AB  - We report on the association of absent patellae, genital and renal anomalies,
      dysmorphic features, and mental retardation in seven children (six boys and one
      girl) belonging to five unrelated families. Flexion deformities of the knees and
      hips with club feet and absent patellae were consistently observed and scrotal
      hypoplasia and cryptorchidism were present in all boys (6/6). Dysmorphic features
      included a coarse face, a large nose with a high nasal bridge, and microcephaly.
      Other features included renal anomalies (multicystic kidneys or hydronephrosis,
      7/7), agenesis of the corpus callosum (4/7), swallowing difficulties,
      micrognathia (4/7), and pulmonary hypoplasia (3/7). Bilateral hypoplasia of the
      ischia and brachydactyly were also consistently observed (5/5). In two out of
      seven cases, prenatal ultrasound detection of microcephaly and renal anomalies
      led to termination of the pregnancy at 27 weeks. Three children died during the
      first years of life and the remaining two who survived exhibit severe
      developmental delay. High resolution cytogenetic studies performed on lymphocytes
      or fibroblasts or both were normal in all cases. Recurrence in two families
      suggests an autosomal recessive mode of inheritance. We propose that this unusual
      association, similar to that observed in a 4 year old boy by Goldblatt et al,
      represents a new syndrome distinct from previously reported hypoplastic patella
      syndromes.

PMID- 10882754
TI  - Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans
      with familial hypercholesterolaemia.
AB  - In South Africa, the high prevalence of familial hypercholesterolaemia (FH) among
      Afrikaners, Jews, and Indians as a result of founder genes is in striking
      contrast to its reported virtual absence in the black population in general. In
      this study, the molecular basis of primary hypercholesterolaemia was studied in
      16 Africans diagnosed with FH. DNA analysis using three screening methods
      resulted in the identification of seven different mutations in the coding region
      of the low density lipoprotein (LDLR) gene in 10 of the patients analysed. These
      included a 6 bp deletion (GCGATG) accounting for 28% of defective alleles, and
      six point mutations (D151H, R232W, R385Q, E387K, P678L, and R793Q) detected in
      single families. The Sotho patient with missense mutation R232W was also
      heterozygous for a de novo splicing defect 313+1G-->A. Several silent
      mutations/polymorphisms were detected in the LDLR and apolipoprotein B genes,
      including a base change (g-->t) at nucleotide position -175 in the FP2 LDLR
      regulatory element. This promoter variant was detected at a significantly higher
      (p<0.05) frequency in FH patients compared to controls and occurred in cis with
      mutation E387K in one family. Analysis of four intragenic LDLR gene polymorphisms
      showed that the same chromosomal background was identified at this locus in the
      four FH patients with the 6 bp deletion. Detection of the 6 bp deletion in Xhosa,
      Pedi, and Tswana FH patients suggests that it is an ancient mutation predating
      tribal separation approximately 3000 years ago.

PMID- 10882756
TI  - Maternal uniparental heterodisomy of chromosome 14: chromosomal mechanism and
      clinical follow up.
AB  - To our knowledge, 22 cases of chromosome 14 maternal uniparental disomy
      (UPD(14)mat) have been reported so far. The majority of cases were ascertained
      because of an abnormal phenotype associated with a Robertsonian translocation
      involving chromosome 14. We report here on a child with UPD(14)mat detected
      prenatally and resulting from trisomy rescue in a maternal meiosis I non
      disjunction trisomic zygote. After four years of clinical follow up, in addition
      to intrauterine growth retardation (IUGR), only short stature and small hands and
      feet were observed. These clinical data as well as the ascertainment and
      mechanism of origin of UPD(14)mat were compared with those observed in previously
      reported cases. It appears that the clinical spectrum of UPD(14)mat is milder in
      our patient than in patients with UPD(14)mat resulting from other chromosomal
      mechanisms. In addition, a hypothesis based on abnormal imprinting is proposed to
      explain the variability of the UPD(14)mat.

PMID- 10882757
TI  - Molecular cytogenetic characterisation of partial trisomy 9q in a case with
      pyloric stenosis and a review.
AB  - Partial trisomy 9q represents a rare and heterogeneous group of chromosomal
      aberrations characterised by various clinical features including pyloric
      stenosis. Here, we describe the case of a 1 year old female patient with
      different dysmorphic features including pyloric stenosis and prenatally detected
      partial trisomy 9q. This partial trisomy 9q has been analysed in detail to
      determine the size of the duplication and to characterise the chromosomal
      breakpoints. According to the data gained by different molecular cytogenetic
      techniques, such as fluorescence in situ hybridisation (FISH) with whole and
      partial chromosome painting probes, yeast artificial chromosome (YAC) probes, and
      comparative genomic hybridisation (CGH), the derivative chromosome 9 can be
      described as dup(9)(pter-->q22. 1::q31.1-->q22.1::q31.1--> q22.1::q31.1-->qter).
      Four breakpoint spanning YACs have been identified (y806f02, y906g6, y945f5, and
      y747b3) for the proximal breakpoint. According to this new case and previously
      published data, the recently postulated putative critical region for pyloric
      stenosis can be narrowed down to the subbands 9q22.1-q31.1 and is the result of
      either partial trisomy of gene(s) located in this region or a gene disrupted in
      9q31.

PMID- 10882758
TI  - Two novel germline mutations of the retinoblastoma gene (RB1) that show
      incomplete penetrance, one splice site and one missense.

PMID- 10882759
TI  - Mutational germline analysis of hMSH2 and hMLH1 genes in early onset colorectal
      cancer patients.

PMID- 10882760
TI  - Alstrom syndrome: confirmation of linkage to chromosome 2p12-13 and phenotypic
      heterogeneity in three affected sibs.

PMID- 10882761
TI  - Evaluation of the HOX11L1 gene as a candidate for congenital disorders of
      intestinal innervation.

PMID- 10882762
TI  - Reducing the risk of high-order multiple pregnancy after ovarian stimulation with
      gonadotropins.
AB  - BACKGROUND: The incidence of multiple gestation after therapy for infertility is
      especially high among women in whom ovulation is induced with gonadotropins.
      Whether the number of high-order multiple pregnancies (those with three or more
      fetuses) can be reduced is not known. METHODS: We analyzed data on 3347
      consecutive treatment cycles in 1494 infertile women, 441 of which resulted in
      pregnancy. The data collected included the peak serum estradiol concentration,
      the number of follicles 16 mm or larger in diameter, and the total number of
      follicles on the day of induction of ovulation with human chorionic gonadotropin.
      Receiver-operating-characteristic curves and ordinal logistic-regression analyses
      were used to identify values that predicted multiple conceptions. RESULTS: Among
      the 441 pregnancies, 314 resulted from the conception of singletons, 88 of twins,
      22 of triplets, 10 of quadruplets, 5 of quintuplets, and 2 of sextuplets. Neither
      the number of follicles 16 mm or larger nor peak serum estradiol concentrations
      greater than 2000 or 2500 pg per milliliter (7342 or 9178 pmol per liter) (the
      cutoff values currently in wide use) were significantly associated with the
      incidence of high-order multiple pregnancy. However, increasing total numbers of
      follicles and increasing peak serum estradiol concentrations correlated
      significantly with an increasing risk of high-order multiple pregnancy (P<0.001),
      as did younger age (P=0.008). The risk of high-order multiple pregnancy was
      significantly increased in women with a peak serum estradiol concentration of
      1385 pg per milliliter (5084 pmol per liter) or higher (multivariate odds ratio,
      1.9; 95 percent confidence interval, 1.3 to 2.8) or with seven or more follicles
      (multivariate odds ratio, 2.1; 95 percent confidence interval, 1.2 to 3.9) on the
      day of induction of ovulation. CONCLUSIONS: Gonadotropin stimulation that is less
      intensive than is currently customary may reduce the incidence of high-order
      multiple pregnancy in infertile women, though only to a limited extent and at the
      expense of overall pregnancy rates.

PMID- 10882763
TI  - Treatment of acute myocardial infarction and 30-day mortality among women and
      men.
AB  - BACKGROUND: Previous studies have suggested that women with acute myocardial
      infarction receive less aggressive therapy than men. We used data from the
      Cooperative Cardiovascular Project to determine whether women and men who were
      ideal candidates for therapy after acute myocardial infarction were treated
      differently. METHODS: Information was abstracted from the charts of 138,956
      Medicare beneficiaries (49 percent of them women) who had an acute myocardial
      infarction in 1994 or 1995. Multivariate analysis was used to assess differences
      between women and men in the medications administered, the procedures used, the
      assignment of do-not-resuscitate status, and 30-day mortality. RESULTS: Among
      ideal candidates for therapy, women in all age groups were less likely to undergo
      diagnostic catheterization than men. The difference was especially pronounced
      among older women; for a woman 85 years of age or older, the adjusted relative
      risk was 0.75 (95 percent confidence interval, 0.68 to 0.83). Women were somewhat
      less likely than men to receive thrombolytic therapy within 60 minutes (adjusted
      relative risk, 0.93; 95 percent confidence interval, 0.90 to 0.96) or to receive
      aspirin within 24 hours after arrival at the hospital (adjusted relative risk,
      0.96; 95 percent confidence interval, 0.95 to 0.97), but they were equally likely
      to receive beta-blockers (adjusted relative risk, 0.99; 95 percent confidence
      interval, 0.95 to 1.03) and somewhat more likely to receive angiotensin
      converting-enzyme inhibitors (adjusted relative risk, 1.05; 95 percent confidence
      interval, 1.02 to 1.08). Women were more likely than men to have a do-not
      resuscitate order in their records (adjusted relative risk, 1.26; 95 percent
      confidence interval, 1.22 to 1.29). After adjustment, women and men had similar
      30-day mortality rates (hazard ratio, 1.02; 95 percent confidence interval, 0.99
      to 1.04). CONCLUSIONS: As compared with men, women receive somewhat less
      aggressive treatment during the early management of acute myocardial infarction.
      However, many of these differences are small, and there is no apparent effect on
      early mortality.

PMID- 10882764
TI  - Primary prevention of coronary heart disease in women through diet and lifestyle.
AB  - BACKGROUND: Many lifestyle-related risk factors for coronary heart disease have
      been identified, but little is known about their effect on the risk of disease
      when they are considered together. METHODS: We followed 84,129 women
      participating in the Nurses' Health Study who were free of diagnosed
      cardiovascular disease, cancer, and diabetes at base line in 1980. Information on
      diet and lifestyle was updated periodically. During 14 years of follow-up, we
      documented 1128 major coronary events (296 deaths from coronary heart disease and
      832 nonfatal infarctions). We defined subjects at low risk as those who were not
      currently smoking, had a body-mass index (the weight in kilograms divided by the
      square of the height in meters) under 25, consumed an average of at least half a
      drink of an alcoholic beverage per day, engaged in moderate-to-vigorous physical
      activity (which could include brisk walking) for at least half an hour per day,
      on average, and scored in the highest 40 percent of the cohort for consumption of
      a diet high in cereal fiber, marine n-3 fatty acids, and folate, with a high
      ratio of polyunsaturated to saturated fat, and low in trans fat and glycemic
      load, which reflects the extent to which diet raises blood glucose levels.
      RESULTS: Many of the factors were correlated, but each independently and
      significantly predicted risk, even after further adjustment for age, family
      history, presence or absence of diagnosed hypertension or diagnosed high
      cholesterol level, and menopausal status. Women in the low-risk category (who
      made up 3 percent of the population) had a relative risk of coronary events of
      0.17 (95 percent confidence interval, 0.07 to 0.41) as compared with all the
      other women. Eighty-two percent of coronary events in the study cohort (95
      percent confidence interval, 58 to 93 percent) could be attributed to lack of
      adherence to this low-risk pattern. CONCLUSION: Among women, adherence to
      lifestyle guidelines involving diet, exercise, and abstinence from smoking is
      associated with a very low risk of coronary heart disease.

PMID- 10882765
TI  - The prevalence of antibodies against desmoglein 1 in endemic pemphigus foliaceus
      in Brazil. Cooperative Group on Fogo Selvagem Research.
AB  - BACKGROUND: Pemphigus foliaceus is an autoimmune skin disease mediated by
      autoantibodies against desmoglein 1. The endemic form is thought to have an
      environmental cause. The Terena reservation of Limao Verde in Mato Grosso do Sul,
      Brazil, is a recently identified focus of the disease, with a prevalence of 3.4
      percent in the population. We tested the hypothesis that normal subjects living
      in an endemic area have antibodies against desmoglein 1. METHODS: We used an
      enzyme-linked immunosorbent assay to detect antibodies against desmoglein 1 in
      serum samples from 60 patients with endemic pemphigus foliaceus (fogo selvagem)
      who lived in Limao Verde or elsewhere in Brazil, 372 normal subjects (without
      pemphigus foliaceus) from Limao Verde and surrounding locations, and 126 normal
      subjects from the United States and Japan. RESULTS: Antibodies against desmoglein
      1 were detected in 59 of the 60 patients with fogo selvagem (98 percent) but in
      only 3 of the 126 normal subjects from the United States and Japan (2 percent).
      Antibodies were also detected in 51 of the 93 normal subjects from Limao Verde
      (55 percent) and in 54 of the 279 normal subjects from surrounding areas (19
      percent). Serum samples obtained one to four years before the onset of disease
      were available for five patients; all five had antibodies in the initial serum
      samples, and the onset of disease was associated with a marked increase in
      antibody values. CONCLUSIONS: The prevalence of antibodies against desmoglein 1
      is high among normal subjects living in an area among where fogo selvagem is
      endemic, and the onset of the disease is preceded by a sustained antibody
      response. These findings support the concept that the production of antibodies
      against desmoglein 1 is initiated by exposure to an unknown environmental agent.

PMID- 10882766
TI  - Protection against pemphigus foliaceus by desmoglein 3 in neonates.

PMID- 10882767
TI  - Images in clinical medicine. Patent urachus.

PMID- 10882768
TI  - The immune system. First of two parts.

PMID- 10882769
TI  - Clinical problem-solving. Eyes wide open.

PMID- 10882770
TI  - Looking forward to serving you every week.

PMID- 10882771
TI  - In treating infertility, are multiple pregnancies unavoidable?

PMID- 10882772
TI  - Pemphigus--decoding the cellular language of cutaneous autoimmunity.

PMID- 10882774
TI  - Correction: Case 12-2000.

PMID- 10882773
TI  - Advances in Immunology -- A New Series of Review Articles.

PMID- 10882775
TI  - Correction: Treatment of Acromegaly.

PMID- 10882776
TI  - Expression of complement messenger RNAs by human endothelial cells.
AB  - This study evaluated complement mRNA expression in human brain microvessel
      endothelial cells (HBMEC), human umbilical vein endothelial cells (HUVEC), and
      cells of the human derived ECV304 line. Cerebral endothelial cells and HUVEC
      expressed detectable levels of complement gene mRNAs for the C1q B-chain, C1r,
      C1s, C2, C3, C4, C5, C7, C8 gamma-subunit and C9. In addition to C6 mRNA, C1q and
      C9 were not detected in ECV304 cells. These results indicate that endothelial
      cells may be a source of complement proteins in brain and other organs of the
      body.

PMID- 10882777
TI  - A subset of periglomerular neurons in the rat accessory olfactory bulb may be
      excited by GABA through a Na(+)-dependent mechanism.
AB  - The periglomerular (PG) cells of the accessory olfactory bulb (AOB) are GABAergic
      interneurons which receive input from the vomeronasal sensory neurons and form
      dendrodendritic synapses with each other and with mitral cells. Their
      electrophysiological properties have not been investigated. We have developed a
      novel method of isolating PG cells from the AOB, and used the whole-cell patch
      and gramicidin-perforated patch clamp techniques to measure their basic
      electrophysiological characteristics and their response to GABA. PG cells were
      found to be excitable neurons with voltage-gated Na(+) and K(+) currents, though
      it was very difficult to get PG cells to fire an action potential. The voltage
      gated Na(+) currents of PG cells activate at more positive potentials than those
      of typical CNS neurons. PG cells respond to GABA with currents in which GABA(A)
      receptors play a significant role. A subset ( approximately 40%) of PG cells
      respond to GABA with currents which have unusually high reversal potentials,
      indicating that GABA may be excitatory to these neurons. This phenomenon cannot
      be explained entirely by elevation of intracellular chloride concentrations, and
      is dependent on the presence of extracellular sodium.

PMID- 10882778
TI  - Influence of serotonin on the kinetics of vesicular release.
AB  - The mechanisms by which synaptic vesicles are transported and primed to fuse with
      the presynaptic membrane are important to all chemical synapses. Processes of
      signal transduction that affect vesicular dynamics, such as the second-messenger
      cascades induced by neuromodulators, are more readily addressed in assessable
      synaptic preparations of neuromuscular junctions in the crayfish. We assessed the
      effects of serotonin (5-HT) through the analysis of the latency jitter and the
      quantal parameters: n and p in the opener muscle of the walking leg in crayfish.
      There is an increase in the size of the postsynaptic currents due to more
      vesicles being released. Quantal analysis reveals a presynaptic mechanism by an
      increase in the number of vesicles being released. Latency measures show more
      events occur with a short latency in the presence of 5-HT. No effect on the
      frequency or size of spontaneous release was detected. Thus, the influence of 5
      HT is presynaptic, leading to a release of more vesicles at a faster rate.

PMID- 10882779
TI  - Chronic peripheral administration of the angiotensin II AT(1) receptor antagonist
      candesartan blocks brain AT(1) receptors.
AB  - Brain Angiotensin II, through stimulation of brain AT(1) receptors, regulates
      pituitary hormones and autonomic activity. We have administered the
      insurmountable AT(1) antagonist Candesartan, s.c. via osmotic minipumps for 14
      days, to determine whether peripheral chronic AT(1) blockade affects AT(1)
      receptor binding and mRNA in the brain. Peripherally administered Candesartan
      (0.1, 0.5 or 1.0 mg/kg per day) inhibits AT(1) binding in adrenal gland zona
      glomerulosa and kidney glomeruli. In addition, Candesartan dose-dependently
      decreases AT(1) binding in brain areas outside (subfornical organ and area
      postrema) and inside (paraventricular nucleus of the hypothalamus and nucleus of
      the solitary tract) the blood-brain barrier. Conversely, peripheral treatment
      with Candesartan does not affect AT(1A) receptor mRNA, the predominant receptor
      subtype expressed in these areas, or Angiotensin II binding to AT(2) receptors in
      the locus coeruleus or inferior olive. Our results demonstrate that chronic
      peripheral treatment with selective, potent AT(1) antagonists not only inhibits
      peripheral but also brain AT(1) receptors. These central effects may play a role
      in the antihypertensive effects of the AT(1) antagonist Candesartan.

PMID- 10882780
TI  - Receptor blockade reveals a correspondence between hippocampal-dependent behavior
      and experience-dependent synaptic enhancement.
AB  - This study examined the involvement of N-methyl-D-aspartate receptors (NMDARs) in
      experience-dependent synaptic plasticity. Rats chronically received an NMDA
      receptor antagonist (AP5) or saline (SAL) and were exposed to individual cages
      (IC) or environmental enrichment (EC). AP5 impaired measures of hippocampal
      dependent behavior and increased locomotor activity. Perforant path synaptic
      strength, measured in the in vitro hippocampal slice, was increased and long-term
      potentiation (LTP) was decreased for EC+SAL animals. The experience-dependent
      effects on synaptic function were inhibited by drug treatment. Measures of
      synaptic strength were correlated with hippocampal-dependent behavior and
      synaptic plasticity for EC animals. The results suggest a relationship between
      hippocampal-dependent behavior and experience-dependent modification of perforant
      path synaptic function through NMDAR activation.

PMID- 10882781
TI  - Aproteic diet decreases hypothalamic catecholamine turnover in adult male rats.
AB  - Previous reports indicate that malnutrition reduces reproductive functions. We
      have demonstrated that protein deprivation in the diet also causes reproductive
      dysfunction by reducing hypothalamic GnRH secretion. Noradrenaline and nitric
      oxide are modulators of GnRH secretion. Noradrenaline stimulates GnRH secretion
      and nitric oxide inhibits catecholamine release. This work studies the
      hypothalamic catecholaminergic and nitrergic neuron activity in Wistar adult male
      rats fed on an aproteic diet (AP) during 21 days; this treatment was started when
      rats were 70 days old. Our first experiment studied catecholamine turnover rate
      after inhibition of tyrosine hydroxylase activity by injecting (i.p.) 400 mg/kg
      alpha-methyl-p-tyrosine. Our second experiment studied in vitro hypothalamic
      nitric oxide synthase (NOS) activity in animals under the same diet. AP diet
      significantly decreased both noradrenaline (P<0.05) and dopamine (P<0.05)
      hypothalamic turnover rate. Noradrenaline turnover in cerebral cortex was not
      altered by the aproteic diet. However, hypothalamic NOS activity was not affected
      in animals fed on an AP diet. These results indicate that the lack of protein in
      the diet reduces catecholaminergic neuron activity in adult male rats by a NO
      independent mechanism, thus suggesting that a decrease in noradrenergic activity
      may be involved in the reduction of GnRH secretion induced by an AP diet.

PMID- 10882782
TI  - Polysynaptic neural pathways between the hypothalamus, including the
      suprachiasmatic nucleus, and the liver.
AB  - The suprachiasmatic nucleus of the hypothalamus is responsible for a 24-h rhythm
      in basal glucose levels in the rat. The neural pathways used by the
      suprachiasmatic nucleus to mediate this rhythm in plasma glucose have not yet
      been identified. In the present study we examined whether there are any
      connections between hypothalamic centers, including the suprachiasmatic nucleus,
      and the liver, which is the main site for glucose production and storage.
      Transneuronal virus tracing from the liver showed that after injection of
      pseudorabies virus, specific neuronal cell populations in the central nervous
      system were labeled retrogradely, suggesting that specific sites in the central
      nervous system may control liver metabolism. First-order neurons belonged to the
      sympathetic and parasympathetic system, while second-order and third-order
      neurons were present in both the brainstem and hypothalamus. The presence of
      third-order neurons in the suprachiasmatic nucleus suggests an involvement of the
      biological clock in the neural control of the liver.

PMID- 10882783
TI  - Acute inflammatory reaction following experimental intracerebral hemorrhage in
      rat.
AB  - Previous studies on intracerebral hemorrhage (ICH) indicate that brain edema
      increases progressively in the first 24 h and remains elevated for several days.
      The cause of secondary brain injury and edema formation is uncertain. We
      hypothesized that inflammatory mediators released from the blood after cerebral
      hemorrhage might cause secondary brain injury and edema formation. This study
      investigates if, when and where inflammation occurs after ICH in rat.
      Immunocytochemistry for polymorphonuclear leukocyte marker (myeloperoxidase,
      MPO), microglia marker (OX42) and intracellular adhesion molecule-1 (ICAM-1) was
      performed in control, and 1, 3, 7 and 10 days after the injection of 100
      microliter autologous blood in the right basal ganglia. Double labeling
      immunohistochemistry was used to identify ICAM-1 positive cells. The results show
      that an inflammatory response occurred in and around the blood clot after ICH,
      characterized by the infiltration of neutrophils and macrophages as well as
      activation of microglia. ICAM-1 immunoreactivity was observed in blood vessels
      adjacent to the clot, as well as in activated microglia and neurons in the
      ipsilateral hemisphere. The present study demonstrates there is an inflammatory
      response in the brain after ICH. Infiltrating leukocytes and activated microglia
      may release cytotoxic mediators contributing to secondary brain injury.

PMID- 10882784
TI  - Reduced nicotinic receptor-mediated antinociception following in vivo antisense
      knock-down in rat.
AB  - Pharmacological activation of neuronal nicotinic acetylcholine receptors can
      produce non-opioid antinociception in rodents. However, multiple nAChR subtypes
      exist, the most abundant of which contain alpha4 and beta2 subunits. The purpose
      of the present study was to investigate the role of alpha4-containing nAChRs in
      mediating nicotinic antinociception using an in vivo antisense strategy. Both
      i.c.v. infusion and repeated bolus injections into the cerebral aqueduct of an
      antisense oligonucleotide against the alpha4 subunit significantly attenuated the
      antinociceptive effects of the nAChR agonist A-85380 in the paw withdrawal test
      of acute thermal pain. Rats treated with a scrambled oligonucleotide displayed a
      full antinociceptive response to A-85380, while discontinuing antisense treatment
      restored the antinociceptive effects of the nicotinic agonist. Double
      immunohistochemical labeling revealed near-complete overlap of expression of the
      serotonin marker tryptophan hydroxylase and the alpha4 nAChR subunit in the
      dorsal raphe nucleus. The expression of alpha4-containing nAChRs by serotonergic
      neurons in the dorsal raphe offered a means to address nonspecific alpha4 knock
      down, i.e., oligonucleotide-induced neurotoxicity. Immunohistochemical detection
      of alpha4 expression was reduced by nearly 50% in the dorsal raphe of antisense
      treated rats as compared to either saline or missense-treated controls. In
      contrast, the expression of tryptophan hydroxylase, as well as, the alpha7 nAChR
      subunit in antisense-infused rats was similar to that observed in saline- and
      missense-treated controls. The results of these studies suggest that alpha4
      containing nAChRs, possibly expressed by serotonergic neurons, are involved in
      nicotinic-mediated analgesia. However, these data do not eliminate the
      possibility that other nicotinic subunit combinations may also play a role in
      antinociception produced by nAChR activation.

PMID- 10882785
TI  - Activation of the somatosensory cortex during Abeta-fiber mediated hyperalgesia.
      A MSI study.
AB  - OBJECTIVE: To investigate the neural activation in the primary somatosensory
      cortex (SI) that is induced by capsaicin-evoked secondary Abeta-fiber-mediated
      hyperalgesia with magnetic source imaging (MSI) in healthy humans. BACKGROUND:
      Dynamic mechanical hyperalgesia, i.e. pain to innocuous light touching, is a
      symptom of painful neuropathies. Animal experiments suggest that alterations in
      central pain processing occur so that tactile stimuli conveyed in Abeta low
      threshold mechanoreceptive afferents become capable of activating central pain
      signalling neurons. A similar state of central sensitization can be
      experimentally produced with capsaicin. METHODS: In six individuals the
      somatosensory evoked magnetic fields (SEFs) induced by non-painful electrical
      stimulation of Abeta-afferents at the forearm skin were recorded. Capsaicin was
      injected adjacent to the stimulation site to induce secondary dynamic Abeta
      hyperalgesia. Thereafter, the SEFs induced by the identical electrical stimulus
      applied within the secondary hyperalgesic skin were analyzed. The electrical
      stimulus was subsequently perceived as painful without changing the stimulus
      intensity and location. Latencies, anatomical source location and amplitudes of
      SEFs during both conditions were compared. RESULTS: Non-painful electrical
      stimulation of Abeta-afferents induced SEFs in SI at latencies between 20 and 150
      ms. Stimulation of Abeta-afferents within the capsaicin-induced secondary
      hyperalgesic skin induced SEFs at identical latencies and locations as compared
      with the stimulation of Abeta-afferents within normal skin. The amplitudes, i.e.,
      the magnetic dipole strengths of the SEFs were higher during Abeta-hyperalgesia.
      CONCLUSIONS: Acute application of capsaicin produces an increase in the
      excitability of central neurons, e.g., in SI. This might be due to sensitization
      of central neurons so that normally innocuous stimuli activate pain signalling
      neurons or cortical neurons might increase their receptive fields.

PMID- 10882786
TI  - Plastic changes and nitric oxide synthase induction in neurons which innervate
      the regenerated tail of the lizard Gekko gecko. II. The response of dorsal root
      ganglion cells to tail amputation and regeneration.
AB  - The lizard tail regenerates after amputation, which severs the spinal cord and
      spinal nerves. Dorsal root ganglia (DRGs) do not regenerate in the regrowing
      tail, which is innervated by DRGs rostral to the amputation. With Nissl staining,
      NADPH-diaphorase histochemistry and nitric oxide synthase (NOS)
      immunohistochemistry, we investigated NOS expression and its relationship with
      structural changes in DRG neurons of caudotomized lizards. First, by horseradish
      peroxidase retrograde tracing we here provided evidence that the sensory
      innervation of the regenerated tail derives only from the three pairs of DRGs
      rostral to the amputation plane. These ganglia were then analyzed in control
      animals with original intact tail, at 5, 15 and 30 days after caudotomy, and at 8
      months in lizards with mature regenerates. Caudotomy elicited in DRG neurons
      marked hypertrophy that persisted after tail regeneration. In control ganglia,
      most neurons were lightly NADPH-diaphorase-positive, a few were unstained or
      intensely stained. Tail transection elicited marked staining up-regulation, and
      an increase in the proportion of intensely positive neurons. The staining
      intensity peaked in DRG neurons at 15 days and was still significantly increased
      in respect to controls several months after complete tail regeneration. NOS
      immunoreactivity in DRGs matched the histochemical findings. NADPH-diaphorase
      positivity was also enhanced in the dorsal horn superficial laminae of the
      corresponding spinal segments. We demonstrate that transection of the lizard
      spinal nerves, provoked by tail loss, elicits in the axotomized primary sensory
      neurons marked NOS enhancement, which accompanies axon elongation in the
      regrowing tail and persists after the end of this process.

PMID- 10882787
TI  - Impaired two-tone processing at rapid rates in male rats with induced microgyria.
AB  - We previously reported that adult male rats with bilateral induced microgyria
      exhibit deficits in rapid auditory processing, which appear similar to auditory
      processing deficits seen in individuals with developmental language disabilities.
      The current study was designed to further elaborate that finding using an
      improved paradigm in which stimulus duration was uncoupled from testing
      experience and learning effects. Specifically, two-tone stimuli with durations of
      540, 390, 332 and 249 ms were all presented within a single test session in a
      modified operant conditioning paradigm. Subjects were tested over a period of 12
      days using this variable-stimulus format. Results confirmed microgyric male rats
      were impaired only in processing two-tone stimuli presented at rapid rates (i.e.,
      249 ms duration). Thus the current results support the previously observed link
      between focal malformations and deficits in rapid auditory processing.

PMID- 10882788
TI  - Low dose of tetrodotoxin reduces neuropathic pain behaviors in an animal model.
AB  - We hypothesize that the accumulation of tetrodotoxin (TTX) sensitive sodium
      channels in injured dorsal root ganglion (DRG) neurons plays a critically
      important role in the generation of ectopic discharges and mechanical allodynia
      after peripheral nerve injury. Using the segmental spinal nerve (L5) ligation
      model of neuropathic pain, this hypothesis was tested by examining the effect of
      TTX on the mechanical sensitivity of the affected hind paw. Various
      concentrations of TTX were applied topically to the L5 DRG by using chronically
      implanted polyethylene tubing. The data showed that application of TTX at low
      doses (12.5-50 nM), which are far less than those needed for blocking action
      potential conduction, produced a significant elevation of mechanical threshold in
      the paw for foot withdrawals, a sign of reduced allodynic behaviors. The data
      suggest that TTX-sensitive subtypes of sodium channels play an important role in
      maintaining allodynic behaviors in an animal model of neuropathic pain.

PMID- 10882789
TI  - Neurosteroid modulation of embryonic neuronal survival in vitro following anoxia.
AB  - Neurosteroids are synthesized de novo in the brain from cholesterol or peripheral
      steroid precursors and modulate inhibitory gamma-aminobutyric acid (GABA(A)) and
      excitatory N-methyl-D-aspartate (NMDA) receptors. Evidence indicates that
      neurosteroids are neuroprotective and important during neurodevelopment. We
      tested the hypothesis that neurosteroids increase embryonic neuronal survival
      following anoxia in rat embryonic day 18 cerebral cortical cultures to examine
      potential neurosteroid modulation of this insult during early development. Twenty
      four hours after plating in serum-free medium, cultures were exposed to DHEA,
      DHEAS, or allopregnanolone (10(-10), 10(-8), or 10(-6) M), or vehicle, for 24 h
      (n=9 per treatment condition). Cultures were then subjected to anoxia for 2 h and
      subsequently reincubated for 24 h prior to neuron immunostaining with microtubule
      associated protein 2 (MAP-2) antibody. Supernatant from DHEA and DHEAS-exposed
      cultures was tested for 17beta-estradiol metabolite formation by
      radioimmunoassay. DHEA 10(-6) and 10(-8) M significantly increased neuron
      survival by 85-87% following anoxia. DHEAS 10(-6) M significantly increased
      neuron survival by 74% following anoxia, but DHEAS 10(-10) M decreased neuron
      survival after this insult. Allopregnanolone had modest effects on neuron
      survival that did not attain statistical significance. 17beta-Estradiol
      concentrations were below the limit of detection in all specimens tested
      (sensitivity 4.7 nM). Our data indicate that pretreatment with DHEA and DHEAS at
      physiologically relevant concentrations promotes neuronal survival following
      anoxia in embryonic rat cerebral cortical cultures, and that these effects are
      not secondary to 17beta-estradiol metabolite formation. DHEA and DHEAS modulation
      of anoxia in embryonic neurons may be relevant to disorders of neurodevelopment
      involving this insult.

PMID- 10882790
TI  - Lateral parabrachial lesions impair intraperitoneal but not intraventricular
      methylscopolamine-induced taste aversion learning.
AB  - The role of the lateral parabrachial area (lPB) in the acquisition of a delayed
      taste aversion learning task (TAL) was examined by delivering the peripherally
      acting aversive compound, methylscopolamine (MSP), through two different routes,
      intraperitoneal and intraventricular. Consistent with previous anatomical,
      behavioral and molecular work, electrolytic lesions centered at the lPB did
      impair TAL when the MSP was injected intraperitoneally. However, lPB-lesioned
      animals exhibited intact learning capacities when MSP was administered
      intraventricularly. These results are interpreted in terms of the lPB as a
      critical anatomical relay involved in bottom-up visceral processing of aversive
      stimuli and also in relation to the relevance of forebrain structures in TAL.

PMID- 10882791
TI  - Nerve growth factor and neurotrophin-3 modulate the rabies infection of adult
      sensory neurons in primary cultures.
AB  - With the aim of determining if the proportion of rabies virus (RV)-infected adult
      neurons from dorsal root ganglion are affected by in vitro treatment with
      different neurotrophins, experiments using Nerve Growth Factor (NGF), Brain
      Derived Neurotrophic Factor (BDNF) or Neurotrophin-3 (NT-3) as supplements for
      cells in culture were performed. Cultures treated with three different
      concentrations of each of the neurotrophins mentioned were infected with
      Challenge Virus Standard RV strain. An indirect immunoperoxidase technique was
      performed for the detection and counting of infected cells. NGF (2 ngml(-1) and
      10 ngml(-1)) and NT-3 (1 ngml(-1) and 5 ngml(-1)) induced a significant reduction
      of infected neurons. None of the cultures treated with BDNF showed changes in the
      percentage of infected neurons. Likewise, the proportion of infected non-neuronal
      cells (Schwann cells and fibroblasts) was not altered by the treatment with
      neurotrophins. In addition, morphometric analysis of total and virus
      immunoreactive neurons in culture were carried out, the neurotrophin treatment
      induced variations in the profile of neurons preferentially infected, since cell
      diameters in the infected cell population are different in the presence of NGF
      and NT-3. Data presented here could indicate a putative participation of
      neurotrophin receptor or biochemical modifications induced by neurotrophin
      treatment that affect the infection. The primary culture of dorsal root ganglion
      cells from adult mice is a very useful model for studying the basic phenomena of
      the RV-neuron interaction.

PMID- 10882792
TI  - Patterns of regional brain activation associated with different forms of motor
      learning.
AB  - To examine the variations in regional cerebral blood flow during execution and
      learning of reaching movements, we employed a family of kinematically and
      dynamically controlled motor tasks in which cognitive, mnemonic and executive
      features of performance were differentiated and characterized quantitatively.
      During 15O-labeled water positron emission tomography (PET) scans, twelve right
      handed subjects moved their dominant hand on a digitizing tablet from a central
      location to equidistant targets displayed with a cursor on a computer screen in
      synchrony with a tone. In the preceding week, all subjects practiced three motor
      tasks: 1) movements to a predictable sequence of targets; 2) learning of new
      visuomotor transformations in which screen cursor motion was rotated by 30
      degrees -60 degrees; 3) learning new target sequences by trial and error, by
      using previously acquired routines in a task placing heavy load on spatial
      working memory. The control condition was observing screen and audio displays.
      Subtraction images were analyzed with Statistical Parametric Mapping to identify
      significant brain activation foci. Execution of predictable sequences was
      characterized by a modest decrease in movement time and spatial error. The
      underlying pattern of activation involved primary motor and sensory areas,
      cerebellum, basal ganglia. Adaptation to a rotated reference frame, a form of
      procedural learning, was associated with decrease in the imposed directional
      bias. This task was associated with activation in the right posterior parietal
      cortex. New sequences were learned explicitly. Significant activation was found
      in dorsolateral prefrontal and anterior cingulate cortices. In this study, we
      have introduced a series of flexible motor tasks with similar kinematic
      characteristics and different spatial attributes. These tasks can be used to
      assess specific aspects of motor learning with imaging in health and disease.

PMID- 10882793
TI  - Hyperbaric oxygenation induced tolerance against focal cerebral ischemia in mice
      is strain dependent.
AB  - SV129 or C57BL/6 mice were exposed to hyperbaric oxygenation (HBO, 5 days, 1 h
      every day, 100% O(2) at 3 atm absolute). One day after the 5th HBO session focal
      cerebral ischemia was induced. In SV129 mice, HBO induced tolerance against
      permanent focal cerebral ischemia (n=42, mean infarct volume reduction 27%,
      P=0.001), but not against transient (30 or 60 min) focal cerebral ischemia. In
      the C57BL/6 strain of mice, HBO did not induce tolerance against focal cerebral
      ischemia, even when the duration of ischemia or the HBO protocol were modified.
      For the first time we demonstrate that HBO can induce tolerance to focal cerebral
      ischemia, but this effect is strain dependent.

PMID- 10882794
TI  - Head movements and neck muscle activities associated with the jaw movement during
      mastication in the rabbit authors.
AB  - Rhythmical head movements and neck muscle activities associated with the
      masticatory jaw movement were investigated in rabbits. In natural mastication,
      head movements and neck muscle activities showed a rhythmical feature
      synchronized with jaw movement. During cortically induced rhythmical jaw
      movements, some neck muscle showed rhythmical activity induced by biting a wooden
      stick. Neck muscles may contribute to the rhythmical head movement after loading
      the tooth with food.

PMID- 10882795
TI  - Effects of MK-801 on D1 dopamine receptor-mediated immediate early gene
      expression in the dopamine-depleted striatum.
AB  - Previous work indicates that intrastriatal administration of MK-801 does not
      completely block D1 agonist-induced gene expression in dopamine-depleted rats.
      The present study examined the effects of systemic MK-801 on such gene
      expression. A low dose of MK-801 did not affect induction of c-fos or zif268. A
      high dose completely blocked induction of c-fos, but only slightly suppressed
      zif268. The data suggest that NMDA receptor activity may not always be necessary
      for D1-induced gene expression.

PMID- 10882796
TI  - Involvement of caspase 3-like protease in methylmercury-induced apoptosis of
      primary cultured rat cerebral microglia.
AB  - Methylmercury (MeHg) has been implicated to induce massive neurodegeneration by
      disruption of neuron-glia interactions besides a direct potent neurotoxicity. In
      the present study, we examined potential cytotoxic effects of MeHg on primary
      cultured rat microglia. Following treatment with a relatively low concentration
      (0.5 microM) of MeHg, microglia had induced cell death accompanied by DNA
      fragmentation and an activation of caspase-3-like protease. MeHg-induced
      microglial death was significantly suppressed by the caspase-3-like protease
      inhibitor benzyloxycarbonyl-Try-Val-Ala-Asp-fluoromethyl-ketone indicating the
      occurrence of caspase-3-like protease-executed apoptosis. The aspartic protease
      inhibitor pepstatin A had a partial but significant inhibitory effect on MeHg
      induced microglial apoptosis. These results indicate that a relatively low
      concentration of MeHg predominantly induces caspase-3-like protease-executed
      apoptosis of microglia, while the endosomal/lysosomal system is also partially
      involved in the cell death pathway.

PMID- 10882797
TI  - The effective number of a population that varies cyclically in size. I. Discrete
      generations.
AB  - We consider a dioecious population having numbers of males and females that vary
      over time in cycles of length k. It is shown that if k is small in comparison
      with the numbers of males and females in any generation of the cycle, the
      effective population number (or size), N(e), is approximately equal to the
      harmonic mean of the effective population sizes during any given cycle. This
      result holds whether the locus under consideration is autosomal or sex-linked and
      whether inbreeding effective population numbers or variance effective population
      numbers are involved in the calculation of N(e). If, however, only two successive
      generations in the cycle are considered and the population changes in size
      between these generations, the inbreeding effective population number, N(eI),
      differs from the variance effective population number, N(eV). The mutation
      effective population number turns out to be the same as the number derived using
      calculations involving probabilities of identity by descent. It is also shown
      that, at least in one special case, the eigenvalue effective population number is
      the same as N(eV).

PMID- 10882798
TI  - Burst properties of a supergated double-barrelled chloride ion channel.
AB  - The chloride selective channel from Torpedo electroplax, ClC-0, is the prototype
      of a large gene family of chloride channels that behave as functional dimers,
      with channel currents exhibiting two non-zero conductance levels. Each pore has
      the same conductance and is controlled by a subgate, and these have seemingly
      identical fast gating kinetics. However, in addition to the two subgates there is
      a single slower 'supergate' which simultaneously affects both channels. In the
      present paper, we consider a six state Markov model that is compatible with these
      observations and develop approximations as well as exact results for relevant
      properties of groupings of openings, known as bursts. Calculations with kinetic
      parameter values typical of ClC-0 suggest that even simple approximations can be
      quite accurate. Small deviations from the assumption of independence within the
      model lead to marked changes in certain predicted burst properties. This suggests
      that analysis of these properties may be helpful in assessing independence/non
      independence of gating in this type of channel. Based on simulations of models of
      both independent and non-independent gating, tests using binomial distributions
      can lead to false conclusions in each situation. This is made more problematic by
      the difficulty of selecting an appropriate critical time in defining a burst
      empirically.

PMID- 10882799
TI  - Analysis and simulation of a stochastic, discrete-individual model of STD
      transmission with partnership concurrency.
AB  - Deterministic differential equation models indicate that partnership concurrency
      and non-homogeneous mixing patterns play an important role in the spread of
      sexually transmitted infections. Stochastic discrete-individual simulation
      studies arrive at similar conclusions, but from a very different modeling
      perspective. This paper presents a stochastic discrete-individual infection model
      that helps to unify these two approaches to infection modeling. The model allows
      for both partnership concurrency, as well as the infection, recovery, and
      reinfection of an individual from repeated contact with a partner, as occurs with
      many mucosal infections. The simplest form of the model is a network-valued
      Markov chain, where the network's nodes are individuals and arcs represent
      partnerships. Connections between the differential equation and discrete
      individual approaches are constructed with large-population limits that
      approximate endemic levels and equilibrium probability distributions that
      describe partnership concurrency. A more general form of the discrete-individual
      model that allows for semi-Markovian dynamics and heterogeneous contact patterns
      is implemented in simulation software. Analytical and simulation results indicate
      that the basic reproduction number R(0) increases when reinfection is possible,
      and the epidemic rate of rise and endemic levels are not related by 1-1/R(0),
      when partnerships are not point-time processes.

PMID- 10882800
TI  - A competition model for viral inhibition of host cell proliferation.
AB  - Some viruses encode proteins that promote cell proliferation while others, such
      as the human immunodeficiency virus (HIV), encode proteins that prevent cell
      division. It has been hypothesized that the selective advantage determining which
      strategy evolves depends on the ability of the virus to induce a cellular
      environment which maximizes both virus production and cell life span. In HIV, the
      protein that causes cell cycle arrest is Vpr. In this paper, we develop a
      mathematical model, based on difference equations, to study the competition
      between two genotypes of HIV - one that encodes this protein (Vpr+) and one that
      does not (Vpr-). In particular, we are interested in parameters that could be
      different between the in vitro condition, where the Vpr- genotype dominates, and
      the in vivo condition, where the Vpr+ genotype dominates. Our model indicates
      that the infected cell death-rate, the viral half-life, and the dynamics of the
      target cell population all effect the competition dynamics between the Vpr+ and
      Vpr- viral genotypes. Perturbing any of these parameters from the in vitro
      estimates while holding the others fixed has no affect on the competition
      outcome, i. e., the Vpr- genotype dominates. Perturbing the infected cell death
      rate and the target cell source causes a switch in competitive outcome, although
      not necessarily at values, which represent the in vivo condition. Adding a
      perturbation in the viral half-life from in vitro to in vivo condition results in
      a switch of the competitive advantage from the Vpr- genotype to the Vpr+ genotype
      with parameters for all three mechanisms set to estimated in vivo values.

PMID- 10882801
TI  - A numerically efficient model for simulation of defibrillation in an active
      bidomain sheet of myocardium.
AB  - Presented here is an efficient algorithm for solving the bidomain equations
      describing myocardial tissue with active membrane kinetics. An analysis of the
      accuracy shows advantages of this numerical technique over other simple and
      therefore popular approaches. The modular structure of the algorithm provides the
      critical flexibility needed in simulation studies: fiber orientation and membrane
      kinetics can be easily modified. The computational tool described here is
      designed specifically to simulate cardiac defibrillation, i. e., to allow
      modeling of strong electric shocks applied to the myocardium extracellularly.
      Accordingly, the algorithm presented also incorporates modifications of the
      membrane model to handle the high transmembrane voltages created in the immediate
      vicinity of the defibrillation electrodes.

PMID- 10882802
TI  - Radiation protection recommendations as applied to the disposal of long-lived
      solid radioactive waste. ICRP Publication 81.
AB  - The present publication deals with the radiological protection of members of the
      public following the disposal of long-lived solid radioactive waste using the
      'concentrate and retain' strategy. It covers options including shallow land
      burial and deep geological disposal. The recommendations made in this report
      apply to new disposal facilities.The main protection issue concerns exposure that
      may or may not occur in the far future, i.e. a situation of potential exposure.
      Constrained optimisation is the central approach to evaluating the radiological
      acceptability of a waste disposal system. In this context optimisation of
      protection is a judgmental process with social and economic factors being taken
      into account and should be conducted in a structured essentially qualitative
      way.Two broad categories of exposure situations have to be considered: natural
      processes and human intrusion. Application of the radiological protection
      criteria to these two categories of exposure situations is different.In the first
      case, assessed doses or risks arising from natural processes should be compared
      with a constraint of no more than about 0.3 mSv per year or its risk equivalent
      of around 10(-5) per year. With regard to human intrusion, understood here as
      inadvertent human intrusion, the consequences from one or more plausible stylised
      scenarios should be considered in order to evaluate the resilience of the
      repository to such events. The Commission considers that in circumstances where
      human intrusion could lead to doses to those living around the site sufficiently
      high that intervention on current criteria would almost always be justified,
      reasonable efforts should be made at the repository development stage to reduce
      the probability of human intrusion or to limit its consequences. In this respect,
      the Commission has previously advised that an existing(1) annual dose of around
      10 mSv per year may be used as a generic reference level below which intervention
      is not likely to be justifiable. Conversely, an existing(1) annual dose of around
      100 mSv per year may be used as a generic reference level above which
      intervention should be considered almost always justifiable. Similar
      considerations apply in situations where the thresholds for deterministic effects
      in relevant organs are exceeded.The conclusion of the report is that in the
      Commission's view, provided reasonable measures have been taken both to satisfy
      the constraint for natural processes and to reduce the probability or the
      consequences of inadvertent human intrusion, and technical and managerial
      principles have been followed, then radiological protection requirements can be
      considered to have been complied with.

PMID- 10882804
TI  - Chapter 1.

PMID- 10882805
TI  - Chapter 2.

PMID- 10882807
TI  - Chapter 4.

PMID- 10882806
TI  - Chapter 3.

PMID- 10882809
TI  - Structural chemistry and therapeutic intervention of protein-protein interactions
      in immune response, human immunodeficiency virus entry, and apoptosis.
AB  - Protein-protein interactions involved in diverse biological functions are largely
      unexplored therapeutic targets, and present a major challenge and opportunity for
      drug design research. Encouraging new approaches to this problem recently have
      emerged from studies of small molecule regulators of protein-protein complexes.
      This review outlines the basic concepts for two of these approaches, based on
      structural and chemical strategies, by illustrating their application in the
      design of small molecule inhibitors for three biological systems: (1) cell
      surface molecules CD4 and CD8 involved in immune response, (2) chemokine receptor
      ligand interactions implicated in human immunodeficiency virus entry, and (3) B
      cell leukemia/lymphoma-2 family proteins essential for regulation of programmed
      cell death or apoptosis. The design and discovery of these novel reagents provide
      valuable tools to probe fundamental questions about a particular protein-protein
      complex, and may lead to a new generation of potential therapeutic agents.
      Furthermore, these studies suggest a framework for chemical intervention of other
      protein-protein interactions involved in many pathological processes.

PMID- 10882810
TI  - Coronary microcirculation: physiology and pharmacology.
AB  - Coronary microvessels play a pivotal role in determining the supply of oxygen and
      nutrients to the myocardium by regulating the coronary flow conductance and
      substance transport. Direct approaches analyzing the coronary microvessels have
      provided a large body of knowledge concerning the physiological and
      pharmacological characteristics of the coronary circulation, as has the rapid
      accumulation of biochemical findings about the substances that mediate vascular
      functions. Myogenic and flow-induced intrinsic vascular controls that determine
      basal tone have been observed in coronary microvessels in vitro. Coronary
      microvascular responses during metabolic stimulation, autoregulation, and
      reactive hyperemia have been analyzed in vivo, and are known to be largely
      mediated by metabolic factors, although the involvement of other factors should
      also be taken into account. The importance of ATP-sensitive K(+) channels in the
      metabolic control has been increasingly recognized. Furthermore, many
      neurohumoral mediators significantly affect coronary microvascular control in
      endothelium-dependent and -independent manners. The striking size-dependent
      heterogeneity of microvascular responses to all of these intrinsic, metabolic,
      and neurohumoral factors is orchestrated for optimal perfusion of the myocardium
      by synergistic and competitive interactions. The regulation of coronary
      microvascular permeability is another important factor for the nutrient supply
      and for edema formation. Analyses of collateral microvessels and subendocardial
      microvessels are important for understanding the pathophysiology of ischemic
      hearts and hypertrophied hearts. Studies of the microvascular responses to drugs
      and of the impairment of coronary microvessels in diseased conditions provide
      useful information for treating microvascular dysfunctions. In this article, the
      endogenous regulatory system and pharmacological responses of the coronary
      circulation are reviewed from the microvascular point of view.

PMID- 10882811
TI  - Ischemic preconditioning: from basic mechanisms to clinical applications.
AB  - When the heart is subjected to a transient nonlethal period of ischemia, it
      quickly adapts itself to become resistant to infarction from a subsequent
      ischemic insult. This adaptation is called preconditioning. This cardioprotection
      has been shown to be mediated by stimulation of receptors linked to protein
      kinase C (PKC) (adenosine, bradykinin, opioids, etc.), and these receptors
      protect by activating PKC. PKC appears to be the first element of a complex
      kinase cascade that is activated during the prolonged ischemia in the
      preconditioned heart. Recent studies imply that p38 mitogen-activated protein
      kinase carries the signal from PKC to the mitochondrial K(ATP) channels, causing
      them to open and thus protect the heart. The cardioprotection of preconditioning
      occurs in all species tested to date, and possibly also humans. It is expected
      that as the mechanism of preconditioning is more thoroughly understood,
      pharmacological preconditioning will become practical for clinical use.

PMID- 10882812
TI  - Neuropharmacology of control of respiratory rhythm and pattern in mature mammals.
AB  - This review summarizes the current understanding of the neurotransmitters and
      neuromodulators that are involved, firstly, in respiratory rhythm and pattern
      generation, where glutamate plays an essential role in the excitatory mechanisms
      and glycine and gamma-aminobutyric acid mediate inhibitory postsynaptic effects,
      and secondly, in the transmission of input signals from the central and
      peripheral chemoreceptors and of motor outputs to respiratory motor neurons.
      Finally, neuronal mechanisms underlying respiratory modulations caused by
      respiratory depressants and excitants, such as general anesthetics,
      benzodiazepines, opioids, and cholinergic agents, are described.

PMID- 10882813
TI  - Sucralose--an overview of the toxicity data.

PMID- 10882814
TI  - Neurotoxicity studies on sucralose and its hydrolysis products with special
      reference to histopathologic and ultrastructural changes.
AB  - Comparative neuropathological studies of 1,6-dichloro-1, 6-dideoxy-beta-D
      fructofuranosyl-4-chloro-4-deoxy-alpha-D-galactopyra  noside (sucralose), an
      equimolar mixture of 1,6-dichloro-1, 6-dideoxyfructose (1,6-DCF) and 4-chloro-4
      deoxygalactose (4-CG), the hydrolysis products of sucralose, and 6-chloro-6
      deoxyglucose (6-CG) were conducted in male and female mice and male marmoset
      monkeys, focusing on morphological changes in the central nervous system. 6
      Chloro-6-deoxyglucose, previously reported to produce neurotoxic effects, served
      as the positive control and was administered by gavage at a daily dose of
      500mg/kg. Sucralose and the sucralose hydrolysis products (sucralose-HP) were
      similarly administered to mice and marmosets at doses of up to 1000mg/kg for 21
      and 28 days, respectively. No changes were detected in the central nervous system
      by light or electron microscopy in either of the species that received sucralose
      or its hydrolysis products. 6-Chloro-6-deoxyglucose, in contrast, induced
      symmetrical lesions in the deep nuclei of the cerebellum, brain stem and spinal
      cord with definitive neurological signs of CNS involvement.

PMID- 10882815
TI  - Sucralose: lack of effects on sperm glycolysis and reproduction in the rat.
AB  - Certain chlorine-substituted sugars with chemical similarities to sucralose have
      been demonstrated previously to diminish or inhibit sperm glycolysis and
      fertility in the rat ([Ford]). In order to investigate this potential for
      sucralose, epididymal spermatozoa were recovered from rats exposed in vivo to
      oral doses of one of three of these substituted sugars: 6-chloroglucose (6-CG,
      24mg/kg/day, positive control), sucralose (500mg/kg/day, over 300 times the
      expected human daily intake), or a 6'-substituted isomer of sucralose, trichloro
      de-oxy sucrose (TCDS, 100mg/kg/day, a potential trace impurity in commercial
      sucralose); distilled water served as the negative control. After incubation of
      the spermatozoa with D-[U-(14)C] glucose, measurements of (14)CO(2) and of ATP
      content showed no impairment of the glycolytic ability of spermatozoa in any of
      the groups except for a marked inhibition for those exposed to 6-CG, the positive
      control. In order to determine whether other parameters of reproduction and
      fertility could be affected, reproductive endpoints were examined following oral
      exposure of male and female rats to sucralose. Sucralose was fed in the diet at
      concentrations of 0, 0.3, 1.0 and 3.0% (approx. 100, 365 and 1150 times the EDI)
      to groups of 30 male and 30 female rats for 10 weeks prior to mating, and
      continued through two subsequent generations until weaning of the F(2) pups. Two
      litters were produced per generation. Food consumption and weight gain in the
      F(0) and F(1) generations were depressed in all sucralose groups before mating
      and in all four litters prior to weaning. The decrease in initial average weight
      for newborn pups probably reflects the increased litter sizes noted for sucralose
      treated groups and the reduced food consumption of the dams during gestation and
      lactation. The latter is a result primarily of the unpalatability of sucralose to
      rats ([McNeil,]). Caecal enlargement (a common animal response to large doses of
      indigestible material) occurred in both the F(0) and F(1) parents. Increased
      kidney weights, possibly associated with increased water intake, were observed
      primarily among animals receiving 3% sucralose (no renal histopathology has been
      detected). Decreased thymus weights occurred in F(1) males and in both F(1) and
      F(2) females at the 3% level. Subsequent studies specifically designed to
      investigate the potential for adverse immune system effects of sucralose
      ([McNeil,]) showed no adverse effects. These findings are consistent with
      investigations by others showing that decreases in thymus weights occur in young
      rats in response to stressful conditions associated with reductions in weight
      gain. All reproductive indices (oestrous cycles, mating behaviour, fertility,
      gestation, maternal and foetal viability, foetal development, parturition, pup
      maturation and lactation) were comparable between the control and sucralose
      treated groups. We conclude from these results that sucralose has no effect on
      sperm glycolysis or on male or female reproductive performance in the rat.

PMID- 10882816
TI  - Sucralose metabolism and pharmacokinetics in man.
AB  - The metabolic and pharmacokinetic profile of sucralose was studied in human
      volunteers. Following a single oral dose of (14)C-sucralose (1mg/kg, 100 microCi)
      to eight male subjects, a mean of 14.5% (range 8.9 to 21.8%) of the radioactivity
      was excreted in urine and 78.3% (range 69.4 to 89.6%) in the faeces, within 5
      days. The total recovery of radioactivity averaged 92.8%. Plasma concentrations
      of radioactivity were maximal at about 2 hours after dosing. The mean residence
      time (MRT) for sucralose was 18.8hr, while the effective half-life for the
      decline of plasma radioactivity was 13hr. Two volunteers given a higher oral dose
      (10mg/kg, 22.7 microCi) excreted a mean of 11.2% (9.6 and 12.7%) of the
      radioactivity in urine, and 85.5% (84.1 and 86.8%) in faeces over 5 days. The
      total recovery of radioactivity was 96.7%. The radiolabelled material present in
      faeces was essentially unchanged sucralose. Sucralose was the principal component
      in the urine together with two more polar components which accounted for only
      2.6% of the administered dose (range 1.5 to 5.1% of dose); both metabolites
      possessed characteristics of glucuronide conjugates of sucralose.

PMID- 10882817
TI  - Sucralose: assessment of teratogenic potential in the rat and the rabbit.
AB  - The teratogenic potential of sucralose was examined following gavage
      administration to pregnant rats and rabbits during organogenesis. Groups of 20
      mated rats were dosed on days 6-15 of gestation inclusive at 500, 1000 or
      2000mg/kg/day; groups of 16 to 18 inseminated rabbits were dosed on days 6 to 19
      of gestation inclusive at 175, 350 or 700mg/kg/day following preliminary studies
      at higher doses. Concurrent control groups received vehicle alone. Rats were
      killed on day 21 and rabbits on day 29 of gestation. Foetuses were evaluated at
      necropsy and after processing for possible soft tissue and skeletal alterations.
      There was no evidence of teratogenicity for either species. The only observed
      response to treatment in rats was a slight increase in water intake. Some adult
      rabbits receiving 700mg/kg/day exhibited marked gastrointestinal disturbance,
      also seen at higher doses in preliminary studies. Gastrointestinal effects such
      as these occur non-specifically in response to high doses of poorly absorbed
      compounds, and in the present study were considered to be responsible for two
      maternal deaths and four abortions. Full evaluation of rabbit foetuses in the
      main study (up to 700mg/kg/day) and necropsy of foetuses in a preliminary study
      with pregnant animals (up to 1000mg/kg/day) showed no evidence of adverse foetal
      response to sucralose. These teratology studies in both pregnant rodent and non
      rodent animal models demonstrate that maternal consumption of high levels of
      sucralose during the period of organogenesis has no effect on normal foetal
      development in the rat or rabbit.

PMID- 10882818
TI  - Acute and subchronic toxicity of sucralose.
AB  - The toxicity of sucralose has been evaluated in acute and subchronic toxicity
      studies. Acute oral toxicity studies in male and female mice and male rats
      documented no deaths or treatment-related signs at doses of 16g/kg for mice and
      10g/kg for rats. Sucralose was administered to male and female rats for 4 and 8
      weeks at dietary concentrations of 1.0, 2.5 or 5.0%. Achieved dose ranges
      (mg/kg/day) for the respective dietary levels were 737-1287, 1865-3218 and 2794
      6406. There were no toxicologically significant effects observed at the 1.0% or
      2.5% dietary levels. However, decreases in food consumption, body weight gain and
      selected organ weights and ratios as well as splenic and thymic histopathologic
      changes occurred in rats administered 5.0% for 4 or 8 weeks. A gavage study
      wherein doses of 0, 750, 1500 or 3000mg/kg/day were administered to male and
      female rats for 26 weeks investigated further the observations from the dietary
      study as well as general subchronic toxicity. The gavage study documented no
      sucralose-related toxicity. These results implicate the reduced palatability and
      digestibility of diets containing high concentrations of sucralose seen in the
      diet study as the cause for the decreased food consumption and other accompanying
      alterations. Dose selection for chronic toxicity studies in rats took into
      consideration the effect of high concentrations of sucralose on digestion and
      food consumption and the limitations that would be imposed on subsequent studies.
      In male and female dogs, no sucralose-related adverse effects were observed
      following the dietary administration of 0.3, 1.0 or 3.0% for 12 months achieving
      doses of approximately 90, 300 and 900mg/kg/day respectively. These studies
      establish that sucralose is non-toxic in rodents following acute oral
      administration. The rat no-observed-adverse-effect level ranged between 2.5 and
      5.0% following subchronic dietary administration. A 3.0% dietary concentration
      equivalent to a dose of 900mg/kg/day produced no adverse effects in beagle dogs
      when fed for 12 months.

PMID- 10882819
TI  - A combined chronic toxicity/carcinogenicity study of sucralose in Sprague-Dawley
      rats.
AB  - The chronic toxicity and potential carcinogenicity of sucralose was evaluated by
      exposing Sprague-Dawley rats to dietary concentrations of this low-calorie
      sweetener both in utero and for up to 104 weeks following parturition. The rats
      assigned to the toxicity phase of this investigation were administered diets
      containing either 0% (control), 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0%
      (30,000 ppm) sucralose. Each treatment group comprised 30 male and 30 female
      rats, of which 15 males and 15 females were sacrificed after 52 weeks of
      treatment. The surviving rats were killed following 78 weeks of sucralose
      administration. In the carcinogenicity phase of this investigation, groups of 50
      male and 50 female rats were administered dietary sucralose at concentrations of
      0% (control 1), 0% (control 2), 0.3%, 1.0% or 3.0% for 104 weeks. Evaluation of
      the data obtained from the two phases of this study showed that sucralose was not
      carcinogenic. Sucralose did not adversely affect the survival or clinical
      condition of the rats, and there were no toxicologically significant findings.
      Group mean body weight gain and food consumption were significantly decreased in
      a dose-dependent manner in sucralose-treated rats throughout the treatment period
      as compared to the controls. The primary effect of sucralose on food consumption,
      and secondarily on body weight gain, was established in later studies to be due
      to the fact that diets containing high concentrations of sucralose are
      unpalatable to rats. These subsequent studies established that the reduction of
      body weight gain seen in previous rat studies using sucralose in the diet at
      concentrations of 1% and below resulted from reduced food intake as a direct
      consequence of the unpalatable nature of sucralose. Similarly, at concentrations
      of 3% in the diet, it was shown that approximately 95% of the effect on body
      weight gain could be attributed to the reduction in food intake due to the
      reduced palatability of the diet, the remainder apparently due to a physiologic
      response to the high concentrations of non-digestible sucralose in the rats'
      diet. Complete toxicological evaluations of gavage studies with histopathological
      evaluations demonstrated that even at the 3% dietary level, toxicity was not
      responsible for the small body weight gain decrement. Gross and histopathologic
      examinations revealed that the administration of sucralose affected neither the
      types nor incidence of the tumours observed. The incidences of some non
      neoplastic findings were statistically significantly increased in the sucralose
      treated groups relative to the controls. These included: renal pelvic epithelial
      hyperplasia in all female treatment groups, renal pelvic mineralization in
      females administered the intermediate or highest dietary concentrations of
      sucralose, adrenal cortical haemorrhagic degeneration in high-dose group female
      rats, and the histopathologic incidence of cataracts at necropsy in high-dose
      group male rats. The non-neoplastic findings that occurred were of no
      toxicological significance since they were either spontaneous findings commonly
      observed in aged rats of this strain or the physiological response to high
      dietary levels of a poorly absorbed compound.

PMID- 10882821
TI  - The pharmacokinetics and metabolism of sucralose in the dog.
AB  - The pharmacokinetics and metabolism of sucralose were investigated in dogs
      following intravenous or oral administration. Oral doses of (14)C-sucralose were
      rapidly absorbed, although there was some variation in the extent of absorption
      (range 18-48% of the dose). After intravenous or oral administration,
      radioactivity excreted in the urine was associated mainly with unchanged
      sucralose. One urinary metabolite was detected after both intravenous and oral
      doses and was identified by mass spectrometry as a glucuronic acid conjugate of
      sucralose. This metabolite accounted for about 15-20% of the intravenous dose but
      for only about 2-8% of the oral dose.

PMID- 10882820
TI  - A carcinogenicity study of sucralose in the CD-1 mouse.
AB  - The potential carcinogenicity of sucralose was evaluated by feeding groups of 52
      male and 52 female CD-1 mice a diet containing sucralose at 0.3% (3000 ppm), 1.0%
      (10,000 ppm) or 3.0% (30,000 ppm) for 104 weeks. A group of 72 male and 72 female
      mice received diet without sucralose and served as controls. Week 1 achieved
      doses ranging from 543 to 5870mg/kg body weight/day in the low-dose males and
      high-dose females, respectively. Sucralose had no adverse effect on survival. No
      significant changes attributable to sucralose were found in the clinical
      condition or behaviour of the mice. Organ weights and the gross appearance of
      tissues were unaffected by treatment. The mean erythrocyte counts of females
      receiving the highest dietary concentration were slightly, but statistically
      significantly, lower than those of the controls after 104 weeks of treatment.
      Group mean body weight gain at the highest dietary concentration of sucralose was
      significantly less than that of the control in mice of both sexes. Food
      consumption, after correction for sucralose content, was lower for female mice,
      but not statistically significant. Water consumption for male mice receiving the
      highest dietary concentration was approximately 9% higher than that of the
      controls. There were statistically significant increases in the incidence of
      several non-neoplastic findings, but these were not considered to be related to
      sucralose administration. Treatment with sucralose did not increase the incidence
      of any tumour or influence the types of tumours observed. It was concluded that
      sucralose is not carcinogenic in CD-1 mice. The body weight gain and erythrocyte
      observations at the 3.0% dietary level were of limited biological significance as
      they were not accompanied by any histopathologic finding and had no impact on
      survival. The remaining dose levels were judged to have no effects.

PMID- 10882822
TI  - The pharmacokinetics and metabolism of sucralose in the mouse.
AB  - The excretion and metabolism of (14)C-sucralose has been investigated in mice
      following intravenous and oral administration. A 20mg/kg intravenous dose was
      rapidly excreted mainly in the urine (80% in 5 days). After 100, 1500 and
      3000mg/kg oral doses of (14)C-sucralose, means of 23%, 15% and 16% of the dose,
      respectively, were excreted in the urine during 5 days. Comparison with the
      intravenous dose indicated that 20-30% of the oral doses was absorbed. Sucralose
      was excreted almost entirely unchanged and represented more than 80-90% of the
      radioactivity in all urine and faeces samples. Only two minor metabolites were
      detected, representing 2-8% of urine radioactivity.

PMID- 10882823
TI  - The pharmacokinetics and metabolism of sucralose in the rabbit.
AB  - The excretion and metabolism of (14)C-sucralose has been investigated in non
      pregnant and pregnant rabbits after administration of single 10mg/kg oral doses.
      Means of 22% and 55% of the dose were excreted in urine and faeces, respectively,
      by non-pregnant animals during 5 days. Excretion was similar in pregnant animals
      with means of 22% and 65% of the dose in urine and faeces, respectively, during
      the same time. Following a single oral dose, a mean of approximately 7% of the
      dose was still being excreted during the 96-120-hr collection period. Only one
      major radioactive component was detected in urine samples which corresponded to
      unchanged sucralose.

PMID- 10882824
TI  - The metabolic fate of sucralose in rats.
AB  - The fate of sucralose was investigated in rats following single intravenous or
      oral doses of 2-1000mg/kg. Following intravenous administration (2-20mg/kg)
      approximately 80% of the dose was eliminated in urine with 9-16% in the faeces.
      In contrast, only about 5% of oral doses (10-1000mg/kg) was recovered in the
      urine, indicating that sucralose is poorly absorbed from the intestinal tract.
      After both intravenous and oral administration, the radioactivity excreted in
      urine and faeces was mainly unchanged sucralose. Two minor radioactive urinary
      components were observed, which together accounted for less than 1% of the
      administered dose. Rats which had been given high concentrations of sucralose
      (3%) in the diet for more than 18 months showed a similar metabolic profile,
      demonstrating that metabolic adaptation of the gut microflora or mammalian
      enzymes had not occurred during the treatment period.

PMID- 10882826
TI  - Limbs found in water: investigation using anthropological analysis and the diatom
      test.
AB  - We report the investigation, using a multi-disciplinary approach, of five cases
      of dismembered limbs which were recovered from Lake Ontario, Lake Erie and the
      Niagara River, and examined at the Office of the Chief Coroner for Ontario. In
      all cases, postmortem examination revealed that the limbs had been disarticulated
      in the postmortem period, by non-human taphonomic processes. In addition to
      routine gross examination, the femur and/or tibia were assessed using
      anthropological methods to give estimates of the sex, age, race and stature of
      the individual. The anthropologic data facilitated the identification of one of
      the cases. In all cases, nitric acid extracts of the femoral bone marrow were
      prepared and examined for the presence of diatoms. In all instances, diatom
      frustules were recovered from marrow extracts, indicating that drowning was the
      cause of death or at least a significant contributing factor in the cause of
      death. The use of the diatom test was helpful in excluding the possibility that
      the limbs were dismembered from individuals who had died by means other than
      drowning, and had been subsequently 'dumped' into water. The application of
      anthropological methods and the diatom test for drowning may significantly
      enhance the medico-legal investigation of body parts recovered from water, and we
      present an overview of useful techniques here. Anthropological data may
      facilitate identification, and the diatom test may establish a cause of death.

PMID- 10882825
TI  - Repeated dose study of sucralose tolerance in human subjects.
AB  - Two tolerance studies were conducted in healthy human adult volunteers. The first
      study was an ascending dose study conducted in eight subjects, in which sucralose
      was administered at doses of 1, 2. 5, 5 and 10mg/kg at 48-hour intervals and
      followed by daily dosing at 2mg/kg for 3 days and 5mg/kg for 4 days. In the
      second study, subjects consumed either sucralose (n=77) or fructose (50g/day)
      (n=31) twice daily in single blind fashion. Sucralose dosage levels were
      125mg/day for weeks 1-3, 250mg/day during weeks 4-7, and 500mg/day during weeks 8
      12. No adverse experiences or clinically detectable effects were attributable to
      sucralose in either study. Similarly, haematology, serum biochemistry, urinalysis
      and EKG tracings were unaffected by sucralose administration. In the 13-week
      study, serial slit lamp ophthalmologic examination performed in a random subset
      of the study groups revealed no changes. Fasting and 2-hour post-dosing blood
      sucralose concentrations obtained daily during week 12 of the study revealed no
      rising trend for blood sucralose. Sucralose was well tolerated by human
      volunteers in single doses up to 10mg/kg/day and repeated doses increasing to
      5mg/kg/day for 13 weeks. Based on these studies and the extensive animal safety
      database, there is no indication that adverse effects on human health would occur
      from frequent or long-term exposure to sucralose at the maximum anticipated
      levels of intake.

PMID- 10882827
TI  - Immunohistochemical detection of methadone in the human brain.
AB  - To develop a method of detecting methadone in the human brain by
      immunohistochemistry, brain tissue of frontal cortex, cerebellum, hippocampus,
      basal ganglions and brain stem from victims of a lethal methadone overdose was
      examined. The staining was performed with a monoclonal anti-methadone antibody
      from the mouse, originally developed for immunochemichal purposes (ELISA). With
      the help of the DAKO((R)) Catalyzed Signal Amplification (CSA) System, a specific
      positive immunoreaction was obtained in the neurons of the frontal cortex and
      hippocampus, as compared with specimen from deaths without exposition to
      methadone. Thus, along with metamphetamine, phenobarbital, morphine and insulin,
      immunohistochemical detection is also possible for methadone and the intake of
      this medicament can now be proven morphologically.

PMID- 10882828
TI  - An investigation of the rigor of interpretation rules for STRs derived from less
      than 100 pg of DNA.
AB  - By increasing the PCR amplification regime to 34 cycles, we have demonstrated
      that it is possible routinely to analyse <100 pg DNA. The success rate was not
      improved (without impairing quality) by increasing cycle number further. Compared
      to amplification of 1 ng DNA at 28 cycles, it was shown that increased imbalance
      of heterozygotes occurred, along with an increase in the size (peak area) of
      stutters. The analysis of mixtures by peak area measurement becomes increasingly
      difficult as the sample size is reduced. Laboratory-based contamination cannot be
      completely avoided, even when analysis is carried out under stringent conditions
      of cleanliness. A set of guidelines that utilises duplication of results to
      interpret profiles originating from picogram levels of DNA is introduced. We
      demonstrate that the duplication guideline is robust by applying a statistical
      theory that models three key parameters - namely the incidence of allele drop
      out, laboratory contamination and stutter. The advantage of the model is that the
      critical levels for each parameter can be calculated. This information may be
      used (for example) to determine levels of contamination that can be tolerated
      within the strategy employed. In addition we demonstrate that interpreting one
      banded loci, where allele dropout could have occurred, using LR=1/2f(a) was
      conservative provided that the band was low in peak area. Furthermore, we
      demonstrate that an apparent mis-match between crime-stain and a suspect DNA
      profile does not necessarily result in an exclusion. The method used is complex,
      yet can be converted into an expert system. We envisage this to be the next step.

PMID- 10882829
TI  - Persistent lipsticks and their lip prints: new hidden evidence at the crime
      scene.
AB  - Latent lip print test results produced by permanent lipsticks are presented in
      this work. This cosmetic product, contrary to conventional lipsticks, does not
      leave visible prints and can thus be overlooked at the crime scene. As print
      vehicles the study used ceramics, glass, cotton fabric and paper. Lip prints were
      left to dwell for different periods and were later developed using aluminum
      powder, cobalt oxide powder and magnetic powder. The results show that
      identifiable lip prints can be obtained up to 30 days after being produced.

PMID- 10882830
TI  - Alternative primers for DYS391 typing: advantages of their application to
      forensic genetics.
AB  - The amplification of the STR DYS391, using the primers described in the Genome
      Data Base (GDB: G00-365-251), shows not only an additional band to the Y-specific
      one in males with a size range of 26 bp less than those of DYS391 locus alleles,
      but also a polymorphic pattern in females in the same size range as the
      additional band observed in males. The DYS391 pattern in families reflects a Y
      specific linked locus and also a polymorphic X locus with an X-linked pattern of
      inheritance. A first screening in the X homologous locus allowed the
      identification of five different alleles. Allele frequencies were explored in
      different population groups for both the Y locus and the homologous locus in the
      X chromosome showing a similar allele distribution pattern in the X and Y
      homologous loci. An alternative reverse primer was designed to amplify the Y
      chromosome specific STR in order to improve the specificity and applicability of
      this system to forensic genetics. Comparative results of the amplification with
      the new and the previously described primers proved that with this new primer
      there is a substantial increase in the specificity of the amplification.
      Moreover, a smaller fragment is amplified with a size out of the range of the
      alleles of the other Y-STRs usually used in forensic applications, therefore
      simplifying its inclusion in multiplex systems.

PMID- 10882831
TI  - Experimental blowgun injuries, ballistic aspects of modern blowguns.
AB  - Slender thin arrows blown through modern blowguns can cause serious injuries. In
      this paper we present some data regarding the terminal ballistics of such an
      arrow when blown by a young male who had no previous experience with the weapon.
      The penetration depth into wood was similar to that of an arrow fired from a
      pistol-crossbow. Further, the blowgun arrow could pass through more than 7 mm of
      porcine bone. The velocities at a distance of 2 m from the blowgun of three
      different types of arrows having weights of 1-1.6 g and diameters between 1 and 5
      mm were between 22 and 32 m/s, giving an energy of 0.3 to 0.6 J. When blown from
      a blowgun, these slender modern arrows can thus penetrate human skin and even the
      cranial bone of a child and cause serious injury.

PMID- 10882832
TI  - Determination of chronic methamphetamine abuse by hair analysis.
AB  - A 30-year-old male truck driver, known to be asthmatic, was found dead at the
      roadside lying near his car. A nebulizer bottle of Berotec (fenoterol
      hydrobromide) was found near his hand. The anatomic cause of death was suspected
      to be asthma. Toxicological screening of urine using Triage demonstrated the
      presence of methamphetamine. The blood concentration of methamphetamine was 0.4
      microg/ml, and fenoterol was not detected. Hair analysis clearly indicated
      chronic methamphetamine abuse and medium dependency during the 2 months before
      death. We conclude that death might have been induced by the interaction of
      fenoterol and methamphetamine.

PMID- 10882833
TI  - Distribution of the calcium-binding proteins parvalbumin, calbindin D-28k and
      calretinin in the retina of two teleosts.
AB  - Using monoclonal antibodies against parvalbumin (PV) and calbindin (CB), and a
      polyclonal antiserum against calretinin (CR), the expression patterns of these
      proteins in the retina of the tench and rainbow trout were studied at light
      microscopic level in in toto preparations and radial sections. Parvalbumin was
      present in subpopulations of small amacrine cells in both species, but these
      cells were more abundant and had a clear centre-periphery gradient distribution
      in the tench. Using the McAB 300 monoclonal antibody against CB, glial cells such
      as Muller cells, astrocytes in the nerve fibre layer, and sparse large cells
      close to the entrance of the optic nerve were observed in both species. Moreover,
      this antibody strongly labelled H1 horizontal cells and their thick axon
      terminals in the tench retina, whereas only a small population of amacrine cells
      was stained in the trout. Calretinin was expressed in different types of ganglion
      cells and numerous neurones located in the inner plexiform layer in both species,
      but was more abundant and more strongly stained in the trout retina, where some
      bipolar cells were easily distinguishable. A comparison to current results in
      other vertebrate species is offered.

PMID- 10882834
TI  - Localization of tyrosine hydroxylase-immunoreactivity in the brain of the
      Senegalese sole, Solea senegalensis.
AB  - The localization of catecholamines in the brain of the Senegalese sole was
      determined by immunohistochemical techniques using antibodies against tyrosine
      hydroxylase. Although the general pattern of distribution of catecholamines is
      consistent with that reported in other teleosts, some remarkable differences are
      observed. The most rostral tyrosine hydroxylase immunoreactive (TH-ir) cells were
      identified in the olfactory bulbs, in which a clear asymmetry in the number and
      location of TH-ir perikarya and fibers was observed. The number of TH-ir cells is
      manifestly higher in the right olfactory bulb, especially in the internal cell
      layer. TH-ir fibers are also much more abundant in the right bulb, principally in
      the glomerular and internal cell layers. Other TH-ir cell masses were identified
      in the ventral telencephalon, preoptic area, caudoventral hypothalamus, posterior
      tuberculum, synencephalon, isthmic region and rhombencephalon. Surprisingly, no
      ir cell bodies were identified in the ventromedial thalamic nucleus, which
      exhibits a large number of TH-ir cells in other teleosts. The presence of TH-ir
      fibers in the brain of sole is particularly evident within and around the nuclei
      in which immunoreactive cells are found. However, other zones such as the dorsal
      telencephalon, posterior commissure, optic tectum, torus semicircularis,
      reticular formation or inferior olive also displayed TH-ir fibers. TH-ir axons
      also enter the infundibulum, reaching the proximal pars distalis of the
      adenohypophysis. The distribution of TH-ir cells and fibers is compared with that
      observed in other teleosts and is discussed in a comparative context.

PMID- 10882835
TI  - TrkB-like immunoreactivity in the song system of developing zebra finches.
AB  - The neural song system in zebra finches develops for approximately the first 2
      months after hatching. During that time, male-biased sexual dimorphisms emerge in
      the volume of song control nuclei as well as in the number and size of neurons
      within them. Brain derived neurotrophic factor (BDNF) has been documented in song
      control nuclei at various stages of development. Its high affinity receptor
      (tyrosine kinase B; trkB) is also in the song system, at least at around I month
      of age. The present study was designed to more completely describe the timing and
      potential location of BDNF action by investigating trkB expression during sexual
      differentiation of the song control nuclei. The pattern of immunoreactivity to a
      trkB antibody was examined in male and female zebra finches at post-hatching days
      3-60. Labeling in somata and neuropil appeared to define the telencephalic
      components of the motor pathway (high vocal center and robust nucleus of the
      archistriatum) for song production in males from days 30 to 60, and in females on
      days 45 and 60 (high vocal center). These results are consistent with the
      hypothesis that the receptor, and its ligand BDNF, play a role in processes
      related to song learning in both sexes, including perhaps the motor component
      exhibited by developing males.

PMID- 10882836
TI  - In vivo autoradiography of [3H]SCH 39166 in rat brain: selective displacement by
      D1/D5 antagonists.
AB  - The purpose of this study was to examine the receptor occupancy of D1/D5
      antagonists for D1-like dopamine receptors in rat brain using [3H]SCH 39166, a
      highly selective D1/D5 antagonist with low affinity for 5HT2 receptors. A single
      concentration of triated SCH 39166 was administered to rats, with or without
      competing doses of the Dl/D5 antagonist SCH 23390 and unlabeled SCH 39166. the D2
      like antagonists haloperidol or the 5-HT, antagonist ketanserin. The bound
      radioactivity in the cortex, striatum, nucleus accumbens and olfactory tubercle
      was then quantified using an in vivo autoradiographic procedure. The results
      indicated that [3H]SCH 39166 was dose dependently displaced by the Dl/D5
      antagonists in regions associated with both the nigro-striatal pathway and the
      mesolimbic dopamine pathway, particularly the nucleus accumbens. Neither
      haloperidol nor ketanserin displaced [3H]SCH 39166 in any of the regions
      examined. The data were compared with previously published data examining the in
      vivo binding of [3H]SCH 39166 in rat brain homogenates. The relative values
      obtained were comparable to values detected in rat brain homogenates after in
      vivo binding of [3H]SCH 39166.

PMID- 10882837
TI  - Neuronal projections to the lateral retrochiasmatic area of sheep with special
      reference to catecholaminergic afferents: immunohistochemical and retrograde
      tract-tracing studies.
AB  - The retrochiasmatic area contains the A15 catecholaminergic group and numerous
      monoaminergic afferents whose discrete cell origins are unknown in sheep. Using
      tract-tracing methods with a specific retrograde fluorescent tracer, fluorogold,
      we examined the cells of origin of afferents to the retrochiasmatic area in
      sheep. The retrogradely labeled cells were seen by observation of the tracer by
      direct fluorescence or by immunohistochemistry with specific antibodies raised in
      rabbits or horses. Among the retrogradely labeled neurons, double
      immunohistochemistry for tyrosine hydroxylase, dopamine-beta-hydroxylase, and
      serotonin were used to characterize catecholamine and serotonin FG labeled
      neurons. The retrochiasmatic area, which included the A15 dopaminergic group and
      the accessory supraoptic nucleus (SON), received major inputs from the lateral
      septum (LS), the bed nucleus of the stria terminalis (BNST), the thalamic
      paraventricular nucleus, hypothalamic paraventricular and supraoptic nuclei, the
      perimamillary area, the amygdala, the ventral part of the hippocampus and the
      parabrachial nucleus (PBN). Further, numerous scattered retrogradely labeled
      neurons were observed in the preoptic area, the ventromedial part of the
      hypothalamus. the periventricular area, the periaqueductal central gray (CG), the
      ventrolateral medulla and the dorsal vagal complex. Most of the noradrenergic
      afferents came from the ventro-lateral medulla (Al group), and only a few from
      the locus coeruleus complex (A6/A7 groups). A few dopaminergic neurons
      retrogradely labeled with flurogold were observed in the periventricular area of
      the hypothalamus. Rare serotoninergic fluorogold labeled neurons belonged to the
      dorsal raphe nucleus. Most of these afferents came from both sides of the brain,
      except for hypothalamic supraoptic and paraventricular nuclei. In the light of
      these anatomical data, we compared our results with data obtained from rats, and
      we discussed the putative role of these afferents in sheep in the regulation of
      several specific functions in which the retrochiasmatic area may be involved,
      such as reproduction.

PMID- 10882838
TI  - Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers.
AB  - Groups of subjects whose primary drug of abuse was amphetamine or heroin were
      compared, together with age- and IQ-matched control subjects. The study consisted
      of a neuropsychological test battery which included both conventional tests and
      also computerised tests of recognition memory, spatial working memory, planning,
      sequence generation, visual discrimination learning, and attentional set
      shifting. Many of these tests have previously been shown to be sensitive to
      cortical damage (including selective lesions of the temporal or frontal lobes)
      and to cognitive deficits in dementia, basal ganglia disease, and
      neuropsychiatric disorder. Qualitative differences, as well as some
      commonalities, were found in the profile of cognitive impairment between the two
      groups. The chronic amphetamine abusers were significantly impaired in
      performance on the extra-dimensional shift task (a core component of the
      Wisconsin Card Sort Test) whereas in contrast, the heroin abusers were impaired
      in learning the normally easier intra-dimensional shift component. Both groups
      were impaired in some of tests of spatial working memory. However, the
      amphetamine group, unlike the heroin group, were not deficient in an index of
      strategic performance on this test. The heroin group failed to show significant
      improvement between two blocks of a sequence generation task after training and
      additionally exhibited more perseverative behavior on this task. The two groups
      were profoundly, but equivalently impaired on a test of pattern recognition
      memory sensitive to temporal lobe dysfunction. These results indicate that
      chronic drug use may lead to distinct patterns of cognitive impairment that may
      be associated with dysfunction of different components of cortico-striatal
      circuitry.

PMID- 10882839
TI  - Upregulation of galanin binding sites and GalR1 mRNA levels in the mouse locus
      coeruleus following chronic morphine treatments and precipitated morphine
      withdrawal.
AB  - The neuropeptide galanin and its receptors are expressed in the locus coeruleus
      (LC), a brain area associated with drug dependence and withdrawal. Although
      galanin peptide mRNA levels do not change during withdrawal, it is not known
      whether galanin receptor levels are regulated following opiate withdrawal. This
      study demonstrates that galanin binding in the LC is upregulated by chronic
      intermittent morphine administration or by precipitated withdrawal, but not by
      acute morphine treatment, suggesting that increased activity in the LC may be
      able to regulate galanin binding sites. Moreover, the increase in galanin binding
      sites seems to be caused by increased transcription or stabilization of the
      galanin receptor 1 (GalR1) gene, because there is a dramatic increase in mRNA
      levels following withdrawal in the LC. It is, therefore, possible that the
      increase in GalR1 could be an adaptive mechanism that leads to regulation of cAMP
      levels and possibly firing rate of LC neurons.

PMID- 10882840
TI  - Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of
      cocaine seeking.
AB  - The alpha-2 adrenergic receptor agonists, clonidine, lofexidine and guanabenz,
      blocked stress- but not cocaine-induced reinstatement of cocaine seeking at doses
      that suppressed footshock-induced release of noradrenaline in prefrontal cortex
      and amygdala. Rats were trained to self-administer cocaine (0.5 mg/kg/infusion,
      i.v; 10-12 days) and, after a drug-free period (7-13 days), were returned to the
      self-administration chambers for daily extinction and reinstatement test
      sessions. Both intermittent footshock (15 min, 0.6 mA) and cocaine priming (20
      mg/kg, i.p.) reinstated extinguished drug seeking. Pretreatment with either
      clonidine (20, or 40 microg/kg, i.p.) or lofexidine (50, 100, 150, or 200
      microg/kg, i.p.) attenuated footshock- but not cocaine-induced reinstatement of
      cocaine seeking. Guanabenz (640 microg/kg, i.p.), an alpha-2 agonist with low
      affinity for imidazoline type-1 receptors, also attenuated footshock- but not
      cocaine-induced reinstatement of cocaine seeking. The results point to an
      important role for NE systems in the effects of footshock on relapse to cocaine
      seeking.

PMID- 10882841
TI  - The latent inhibition model dissociates between clozapine, haloperidol, and
      ritanserin.
AB  - Latent inhibition (LI), i.e., retarded conditioning to a stimulus following its
      nonreinforced preexposure, is impaired in some subsets of schizophrenia patients
      and in amphetamine-treated rats. Typical and atypical antipsychotic drugs (APD's)
      potentiate LI, but to date the model has not dissociated between them. This study
      demonstrates such a dissociation using haloperidol (0.1 mg/kg), clozapine (5
      mg/kg), and ritanserin (0.6 mg/kg) administered in preexposure and/or
      conditioning. Under conditions which did not yield LI in vehicle controls (40
      preexposures and five conditioning trials), both haloperidol and clozapine, but
      not ritanserin, led to LI when administered in conditioning. Under conditions
      which led to LI in vehicle controls (40 preexposures and two conditioning
      trials), clozapine and ritanserin, but not haloperidol, abolished LI when
      administered in preexposure. It is suggested that LI potentiation via
      conditioning detects the "typical" action of APD's whereas LI disruption via
      preexposure detects the "atypical" action of APD's.

PMID- 10882842
TI  - Clozapine- and olanzapine-induced Fos expression in the rat medial prefrontal
      cortex is mediated by beta-adrenoceptors.
AB  - The atypical neuroleptics, clozapine and olanzapine, have superior therapeutic
      efficacy against the negative symptoms of schizophrenia, compared with the
      typical neuroleptics. Recently, it has been suggested that the ability of
      clozapine and olanzapine to induce Fos expression in the medial prefrontal cortex
      (mPFC), contribute to their therapeutic efficacy. However, the mechanisms
      underlying the neuropharmacological effects of clozapine and olanzapine in the
      mPFC remain elusive. In the present study, we demonstrate that clozapine- and
      olanzapine-induced Fos expression in the mPFC are inhibited by propranolol. We
      also show that clozapine and olanzapine induce Fos expression in the locus
      coeruleus. These results suggest that clozapine and olanzapine increase
      noradrenaline release by stimulating noradrenergic neuronal activity in the locus
      coeruleus and, consequently, increased noradrenaline induce Fos expression in the
      mPFC via beta-adrenergic receptors. This postulated sequence may be one of
      mechanisms by which clozapine-like atypical neuroleptics are more effective for
      the negative symptoms of schizophrenia.

PMID- 10882843
TI  - Manganese superoxide dismutase gene polymorphism and schizophrenia: relation to
      tardive dyskinesia.
AB  - There has been increasing evidence that deranged superoxide dismutase (SOD)
      activities might be a risk factor for schizophrenia and/or tardive dyskinesia
      (TD). In the present study, we investigated the genetic association between a
      functional polymorphism (Ala-9Val) in the human manganese (Mn) SOD gene and
      schizophrenia or TD (192 schizophrenics: 39 with TD and 153 without TD; 141
      controls). No significant differences in the allelic or genotypic distribution
      between schizophrenics and controls were observed. However, we did find a
      significant difference in genotypic distribution between schizophrenics with and
      those without TD (p =. 03). Moreover, decreased -9Ala (mutant) allele was found
      among patients with TD (p =.02; odds ratio = 0.29; 95% confidence interval = 0.10
      0.83). In conjunction with previous findings of increased free radicals and
      decreased SOD activities in TD subjects, these results suggest that the -9Ala
      (high activity) MnSOD allele may play a role in protecting against susceptibility
      to TD in schizophrenics.

PMID- 10882844
TI  - Diazepam attenuation of somatostatin binding and effect of somatostatin on
      accumulation of inositol 1,4,5-trisphosphate in the rat frontoparietal cortex.
AB  - Numerous reports in both humans and animals have confirmed that benzodiazepines
      produce amnesia; however, mechanisms mediating this effect are not clear. In view
      of the important role of brain somatostatin (SRIF) in the cognitive function of
      rats, this study sought to determine if the benzodiazepine, diazepam, alters
      somatostatinergic system in the rat frontoparietal cortex. Intraperitoneal (i.p.)
      administration of diazepam (5 mg/kg/day) to male Wistar rats (200-250 g) for 3 or
      7 days decreased the number of SRIF receptors (26 and 37%, respectively) in
      synaptosomes from the frontoparietal cortex, without influencing their apparent
      affinity. This decrease in the tracer binding was not attributable to a direct
      effect of diazepam on SRIF receptors, because no decrease of SRIF binding was
      induced by a large concentration of diazepam (10(-4) M) when the drug was added
      to a preparation of synaptosomes from frontoparietal cortex of untreated rats. To
      determine if the effect of diazepam on SRIF binding is related to the binding of
      diazepam to its recognition site on the GABA(A) receptor, a benzodiazepine
      antagonist, 2-phenylpyrazolo[3,4-c]quinolin-3(5H)-one (CGS 8216) was administered
      before the diazepam injection. Pretreatment with CGS 8216 (20 mg/kg/day, i.p.)
      blocked completely the diazepam-induced decrease in the number of SRIF receptors.
      CGS 8216 alone had no observable effect. The decrease in the number of 125I-Tyr11
      SRIF receptor induced by diazepam was accompanied by a decrease in the effect of
      SRIF, after 15 seconds of stimulation, on inositol 1,4, 5-trisphosphate (IP3)
      mass accumulation in the rat frontoparietal cortex at 3 (64%) or 7 days (59%)
      after its administration. Diazepam alone had no observable effect on mass
      accumulation of IP3. After 14 days of daily diazepam injections, the levels of
      binding of 125I-Tyr11-SRIF in the frontoparietal cortex returned to control
      values, coinciding with the tolerance that develops to this benzodiazepine
      agonists when administered chronically. The decrease in IP3 levels was still
      observed after 14 days (57%) diazepam administration. Diazepam and CGS 8216 did
      not affect SRIF-like immunoreactivity levels in the frontoparietal cortex at the
      three time intervals studied (3, 7 or 14 days). The alteration of frontoparietal
      cortex SRIF receptor-effector system after 3 or 7 days of diazepam treatment
      suggests that somatostatinergic neurotransmission plays a role in the mechanism
      of diazepam action on memory.

PMID- 10882845
TI  - Inhibition of synaptosomal uptake of 3H-L-glutamate and 3H-GABA by hyperforin, a
      major constituent of St. John's Wort: the role of amiloride sensitive sodium
      conductive pathways.
AB  - Extracts of St. John's Wort are widely used for the treatment of depressive
      disorders. The active principles have not yet been finally elucidated. We have
      recently shown that hyperforin, a major active constituent of St. John's Wort,
      not only inhibits the neuronal uptake of serotonin, norepinephrine and dopamine,
      but also that of L-glutamate and GABA. No other antidepressant compound exhibits
      a similar broad uptake inhibiting profile. To investigate this unique kind of
      property, kinetic analyses were performed regarding the uptake of 3H-L-glutamate
      and 3H-GABA into synaptosomal preparations of mouse brain. Michaelis-Menten
      kinetics revealed a reduction of Vmax (8.27 to 1.80 pmol/mg/min for 3H-L
      glutamate, 2.76 to 0.77 pmol/mg/min for 3H-GABA) while Km was nearly unchanged in
      both cases, suggesting non-competitive inhibition. The unselective uptake
      inhibition by hyperforin could be mimicked by the Na+-ionophore monensin and by
      the Na+-K+-ATPase inhibitor ouabain. However, both mechanisms can be discarded
      for hyperforin. Several amiloride derivatives known to affect sodium conductance
      significantly enhance 3H-GABA and 3H-L-glutamate uptake and inhibit the uptake
      inhibition by hyperforin, while monensin or ouabain inhibition were not
      influenced. Selective concentrations of benzamil for amiloride sensitive Na+
      channels and selective concentrations of 5'-ethylisopropylamiloride (EIPA) for
      the Na+-H+-exchangers both had an attenuating effect on the hyperforin inhibition
      of L-glutamate uptake, suggesting a possible role of amiloride sensitive Na+
      channels and Na+-H+-exchangers in the mechanism of action of hyperforin.

PMID- 10882846
TI  - Inhibition of cyclic AMP phosphodiesterase (PDE4) reverses memory deficits
      associated with NMDA receptor antagonism.
AB  - Rolipram, a selective inhibitor of type 4 cyclic AMP phosphodiesterase (PDE4),
      completely reversed the amnesic effects of MK-801 on working and reference memory
      (F[4,64] = 11.10; p <.0001 and F[4,64] = 2.53; p <.05, respectively) at doses of
      0.01-0.1 mg/kg in the radial-arm maze task. Similar antagonism by rolipram of the
      effects of MK-801 was observed on inhibitory avoidance behavior (F[3,35] = 190.8;
      p <.0001). In vitro evidence suggests that an increase in cAMP concentrations may
      mediate the observed behavioral effects of rolipram. In the absence of PDE4
      inhibition, NMDA did not increase cAMP concentrations in primary cultures of rat
      cerebral cortical neurons. However, when PDE4 was inhibited with rolipram, NMDA
      markedly elevated cAMP. These observations suggest that PDE4 is an integral
      component of the NMDA receptor-mediated signal transduction pathway involved in
      memory processes. Inhibitors of PDE4 may act on this pathway to produce their
      effects on memory and may represent a new class of cognitive enhancers.

PMID- 10882847
TI  - Long-term repetitive transcranial magnetic stimulation increases the expression
      of brain-derived neurotrophic factor and cholecystokinin mRNA, but not
      neuropeptide tyrosine mRNA in specific areas of rat brain.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a
      therapeutic tool in various neurological and psychiatric disorders, and we
      recently found that it has a neuroprotective effect both in vitro and in vivo.
      However, the neurochemical mechanisms underlying the therapeutic effects are
      still unknown. We investigated the effects of long-term rTMS on the expression of
      brain-derived neurotrophic factor (BDNF), cholecystokinin (CCK), and neuropeptide
      tyrosine (NPY) mRNA in rat brain. In situ hybridization revealed a significant
      increase in BDNF mRNA in the hippocampal areas CA3 and CA3c, the granule cell
      layer, as well as in the parietal and the piriform cortex after rTMS. BDNF-like
      immunoreactivity was markedly increased in the same areas. A significant increase
      in CCK mRNA was observed in all brain regions examined. NPY mRNA expression, in
      contrast, was not altered. The present results suggest that BDNF may contribute
      to the neuroprotective effects of rTMS. Furthermore, the rTMS-induced changes in
      BDNF and CCK expression are similar to those reported after antidepressant drug
      treatment and electroconvulsive seizures, suggesting that a common molecular
      mechanism may underlie different antidepressant treatment strategies.

PMID- 10882848
TI  - Abnormal levels of cAMP-dependent protein kinase regulatory subunits in platelets
      from schizophrenic patients.
AB  - Abnormalities in the cAMP-dependent protein kinase (PKA), a central component of
      cAMP signaling, have been reported in several psychiatric disorders. Previous
      studies showed cAMP signaling alterations in schizophrenic patients but less is
      known about the involvement of PKA in such disorder. Therefore, we investigated
      the PKA subunits by Western blot analysis in platelets from 12 patients with
      schizophrenia and 13 controls. The results showed that the immunolabeling of the
      PKA regulatory subunits type I (RI) and type II (RII) was significantly reduced
      in patients compared with controls whereas no differences were observed in the
      catalytic (C) subunit of the enzyme. These preliminary data suggest that
      schizophrenic patients have altered PKA levels, thus supporting that dysfunctions
      in the components of cAMP signaling may contribute to the pathophysiology of
      schizophrenia.

PMID- 10882849
TI  - Measuring gene-specific nucleotide excision repair in human cells using
      quantitative amplification of long targets from nanogram quantities of DNA.
AB  - We have been developing a rapid and convenient assay for the measurement of DNA
      damage and repair in specific genes using quantitative polymerase chain reaction
      (QPCR) methodology. Since the sensitivity of this assay is limited to the size of
      the DNA amplification fragment, conditions have been found for the quantitative
      generation of PCR fragments from human genomic DNA in the range of 6-24 kb in
      length. These fragments include: (1) a 16.2 kb product from the mitochondrial
      genome; (2) 6.2, 10.4 kb, and 15.4 kb products from the hprt gene, and (3) 13.5,
      17.7, 24.2 kb products from the human beta-globin gene cluster. Exposure of SV40
      transformed human fibroblasts to increasing fluences of ultraviolet light (UV)
      resulted in the linear production of photoproducts with 10 J/m(2) of UVC
      producing 0.085 and 0.079 lesions/kb in the hprt gene and the beta-globin gene
      cluster, respectively. Kinetic analysis of repair following 10 J/m(2) of UVC
      exposure indicated that the time necessary for the removal of 50% of the
      photoproducts, in the hprt gene and beta-globin gene cluster was 7.8 and 24.2 h,
      respectively. Studies using lymphoblastoid cell lines show very little repair in
      XPA cells in both the hprt gene and beta-globin locus. Preferential repair in the
      hprt gene was detected in XPC cells. Cisplatin lesions were also detected using
      this method and showed slower rates of repair than UV-induced photoproducts.
      These data indicate that the use of long targets in the gene-specific QPCR assay
      allows the measurement of biologically relevant lesion frequencies in 5-30 ng of
      genomic DNA. This assay will be useful for the measurement of human exposure to
      genotoxic agents and the determination of human repair capacity.

PMID- 10882850
TI  - Cell-cycle regulation, intracellular sorting and induced overexpression of the
      human NTH1 DNA glycosylase involved in removal of formamidopyrimidine residues
      from DNA.
AB  - Endonuclease III (Nth) of Escherichia coli is a DNA glycosylase essential for the
      removal of oxidised pyrimidine base residues from DNA. Several eukaryotic
      homologues have recently been identified and shown to have biochemical properties
      similar to those of Nth. However, some of the eukaryotic counterparts also appear
      to remove imidazole ring-opened purine residues (faPy), a property not shared by
      the enzymes of bacterial origin. Here, we show that the human enzyme also
      possesses efficient faPy DNA glycosylase activity as indicated both from studies
      of the purified protein and induced overexpression of the human NTH1 cDNA in HeLa
      cells. We constructed green fluorescent protein-tagged hNTH1 fusion proteins to
      study the cellular localisation of hNTH1 and found strong and exclusive sorting
      to the nucleus. Studies with synchronised cells showed that the expression of
      hNTH1 is regulated during the cell cycle with increased transcription during
      early and mid S-phase.

PMID- 10882851
TI  - Deficiency of N-methylpurine-DNA-glycosylase expression in nonparenchymal cells,
      the target cell for vinyl chloride and vinyl fluoride.
AB  - The ability to repair promutagenic damage resulting from exposure to carcinogens
      is a critical factor in determining quantitative relationships in carcinogenesis,
      including the target cell for neoplasia. One major pathway for the repair of
      alkylating agent-induced DNA damage involves removal of alkylated bases by N
      methylpurine-DNA-glycosylase (MPG), the first enzyme in base excision repair. We
      have measured the expression level of MPG mRNA in liver, lung, and kidney of
      Sprague-Dawley rats as a function of age. A quantitative reverse transcriptase
      polymerase chain reaction (QRT-PCR) method was used to measure cellular MPG mRNA.
      MPG mRNA was readily detectable in each tissue analyzed and the age-dependent and
      tissue specific expressions were not statistically different. The lowest amount
      of mRNA was measured in preweanling liver and the highest amounts were found in
      preweanling lung and kidney. Since MPG is reported to be responsible for excision
      of 1,N(6)-ethenoadenine and N(2),3-ethenoguanine, two promutagenic DNA adducts of
      vinyl chloride (VC) and vinyl fluoride (VF), we examined the regulation of this
      enzyme after carcinogen exposure. Expression of MPG was induced in rat liver by
      these carcinogens. In order to determine the repair capacity in different cell
      populations of liver, we measured MPG gene expression in isolated hepatocytes and
      nonparenchymal cells (NPC). The amount of MPG mRNA was 4.5-5 times higher in
      hepatocytes than in NPC of control rats. Induction of MPG expression was observed
      in hepatocytes of VF exposed-rats but not in NPC. The expression of MPG in NPC
      was only 15% of that of the hepatocytes from exposed rats. Western blots of MPG
      protein confirmed the cell type differences, but did not show increased protein
      in exposed vs. control liver and hepatocytes. Since metabolism of VC and VF
      requires CYP2E1, an enzyme exhibiting much greater activity in hepatocytes,
      formation of etheno adducts preferentially occurs in hepatocytes. These data
      suggest that cellular differences in the repair of N-alkylpurines may be a
      critical mechanism in the development of cell specificity in VC carcinogenesis.

PMID- 10882852
TI  - The role of nucleotide excision repair of Escherichia coli in repair of
      spontaneous and gamma-radiation-induced DNA damage in the lacZalpha gene.
AB  - Base excision repair (BER) is a very important repair mechanism to remove
      oxidative DNA damage. A major oxidative DNA damage after exposure to ionizing
      radiation is 7,8-dihydro-8-oxoguanine (8oxoG). 8oxoG is a strong mutagenic
      lesion, which may cause G:C to T:A transversions if not repaired correctly.
      Formamidopyrimidine-DNA glycosylase (Fpg), a repair enzyme which is part of BER,
      is the most important enzyme to repair 8oxoG. In the past years, evidence evolved
      that nucleotide excision repair (NER), a repair system originally thought to
      repair only bulky DNA lesions, can also repair some oxidative DNA damages.
      Examples of DNA damages which are recognized by NER are thymine glycol and abasic
      sites (AP sites). The main objective of this study is to determine if NER can act
      as a backup system for the repair of spontaneous and gamma-radiation-induced
      damages when Fpg is deficient. For that purpose, the effect of a NER-deficiency
      on the spontaneous and gamma-radiation-induced mutation spectrum in the lacZ gene
      was determined, using double-stranded (ds) M13 DNA, with the lacZalpha gene
      inserted as mutational target sequence. Subsequently the DNA was transfected into
      a fpg(-)uvrA(-) Escherichia coli strain (BH420) and the mutational spectra were
      compared with the spectra of a fpg(-) E. coli strain (BH410) and a wild type E.
      coli strain (JM105), which were determined in an earlier study. Furthermore, to
      examine effects which are caused by UvrA-deficiency, and not by Fpg-deficiency,
      the spontaneous and gamma-radiation-induced mutation spectra of an E. coli strain
      in which only UvrA is deficient (BH430) were also determined and compared with a
      wild type E. coli strain (JM105). The results of this study indicate that if only
      UvrA is deficient, there is an increase in spontaneous G:C to T:A transversions
      as compared to JM105 and a decrease in A:T to G:C transitions. The gamma
      radiation-induced mutation spectrum of BH420 (fpg(-)uvrA(-)) shows a significant
      decrease in G:C to A:T and G:C to T:A mutations, as compared to BH410 where only
      Fpg is deficient. Based on these results, we conclude that in our experiments NER
      is not acting as a backup system if Fpg is deficient. Instead, NER seems to make
      mistakes, leading to the formation of mutations.

PMID- 10882854
TI  - Introduction.

PMID- 10882853
TI  - Detection of 8-oxoG DNA glycosylase activity and OGG1 transcripts in the rat CNS.
AB  - The oxoguanine DNA glycosylase (Ogg1) is a DNA repair enzyme that excises 7,8
      dihydro-8-oxoguanine present in DNA damaged by oxidative stress. We have
      investigated the expression of the OGG1 gene in different regions of the rat CNS.
      Biochemical studies on brain homogenates of adult rats have shown that Ogg1
      nicking activity is present at relatively similar levels in the cerebral cortex,
      the hypothalamus, the pons and the cerebellum. Following in situ hybridization
      with radiolabeled OGG1 cDNA or specific antisense oligonucleotides, OGG1
      transcripts showed a widespread but heterogeneous distribution pattern among
      distinct brain regions of adult rats: high levels of this transcript were
      detected in the CA1-CA3 layers and the gyrus dentate of the hippocampal
      formation, the piriform cortex, the supraoptic nuclei, the olivary complex as
      well as in the pyramidal cells of layer V of the cortex and the Purkinje cells of
      the cerebellum. In peripheral organs such as the lungs, the stomach and the
      spleen, OGG1 transcript is however expressed in specific subpopulations of cells.
      Using a semi-quantitative reverse transcription - polymerase chain reaction assay
      on total mRNA from the frontal cortex, OGG1 mRNA was determined to be expressed
      with relatively the same levels in 1-day-old and 7-day-old rats as well as in
      adult rats. These results provide evidence for the widespread expression of the
      OGG1 gene in developing and adult brains.

PMID- 10882855
TI  - Cancer population genetics and tumour prevention: an unfulfilled paradigm.
AB  - The molecular approach to cancer has identified specific abnormalities that
      contribute to malignant pathogenesis in an aetiological manner and define
      individuals who are at higher risk for specific malignancies. Studies of cancer
      distribution in families suggest that 15-20% of all malignancies may have a
      significant germ line hereditable mutation that directly or indirectly
      contributes to tumour development. Additionally, the identification of many
      genetically-determined polymorphisms that regulate carcinogen metabolism indicate
      that their assessment may contribute to selecting individuals for preventive
      surveillance or intervention as well. Locating individuals in the population who
      have moderate to high risk germ line mutations in critical oncogenic regulatory
      genes and assessing a panel of polymorphisms that underlie a significant
      attributable risk for cancer development may allow the recruitment of individuals
      at high risk for a particular malignancy and, therefore, represent good
      candidates for either directed organ surveillance and/or chemoprevention trials.

PMID- 10882856
TI  - Low penetrance genes associated with increased risk for breast cancer.
AB  - Much effort in recent years has been focused on understanding the factors that
      contribute to breast cancer risk. Two major susceptibility alleles, BRCA1 and
      BRCA2, have been identified, and the prevalence and penetrance of mutations in
      these genes have been studied extensively. However, this work highlights the fact
      that only a small proportion of breast cancer is due to mutations in the genes.
      Evidence for additional high penetrance genes exists, but it is becoming clear
      that an understanding of multiple lower penetrance alleles will be necessary to
      fully define breast cancer risk. Work in this area has focused on the analysis of
      polymorphisms of potential functional significance in several classes of genes,
      including those involved in carcinogen metabolism, oestrogen metabolite
      biosynthesis, steroid hormone receptor activation and DNA damage response. These
      studies are reviewed and a strategy to use modification of breast cancer
      penetrance in families with known mutations in BRCA1 as a means of identifying
      additional low penetrance, or modifier, genes is discussed.

PMID- 10882857
TI  - Characteristics of BRCA1 mutations in a population-based case series of breast
      and ovarian cancer.
AB  - Breast and ovarian cancers account for approximately 210000 newly diagnosed cases
      per year. More than half a million American women are estimated to be carriers of
      a breast cancer susceptibility gene. The purpose of this study was to assess the
      association of characteristics such as, age at diagnosis, race/ethnicity and
      family history of cancer with inherited BRCA1 mutations in a population-based
      sample of breast and ovarian cancer cases. No selection was made by race, age at
      diagnosis or positive family history of breast or ovarian cancer. The population
      under study was all breast cancer cases diagnosed in Orange County, CA, during
      the 1-year period beginning 1 March 1994 and all ovarian cancer cases diagnosed
      in Orange County during the 2-year period beginning 1 March 1994. This report
      focuses on the first consecutively ascertained 802 participating probands
      enrolled in the study, of which 9 were male breast cancer probands, 673 were
      female breast cancer probands and 120 were ovarian cancer probands. We observed
      11 BRCA1 mutations or 1.6% (95% CI: 0.8-2.9) among the 673 female breast cancer
      probands and 4 BRCA1 mutations or 3.3% (95% CI: 0.8-8. 3) among the 120 ovarian
      cancer probands. No BRCA1 mutations were identified among the 98 non-white breast
      and ovarian cancer probands. The prevalence of BRCA1 mutations in non-Hispanic
      white breast cancer cases below the age of 50 years was 2%. Positive family
      history of breast or ovarian cancers was significantly associated with BRCA1
      mutation status among breast cancer probands. Similarly, positive family history
      of breast or ovarian cancer was significantly associated with BRCA1 mutation
      status among the ovarian cancer probands. In summary, we present results on the
      prevalence of BRCA1 mutations in a significantly larger sample of population
      based breast and ovarian cancer cases than previously reported. The results
      indicate that, using a conservative approach to targeted genotyping of BRCA1, the
      frequency of mutations was consistent with those reported using similar methods
      of population-based case ascertainment.

PMID- 10882858
TI  - Incidence of BRCA1/2 germ line alterations in a high risk cohort participating in
      a phase II chemoprevention trial.
AB  - It is unknown what proportion of women at high risk for breast cancer, entering
      phase II chemoprevention trials, have BRCA1/2 alterations, and whether their
      initial biomarker patterns or response to preventive interventions will differ
      between carriers and non-carriers. As part of a 6-month phase II chemoprevention
      trial of diflouromethlyornithine (DFMO), high-risk subjects (family history,
      prior precancerous breast disease or prior breast cancer), who had random peri
      areolar fine needle evidence of epithelial hyperplasia with or without atypia,
      were offered genetic counselling and testing at the completion of their study
      participation. 97% of the 119 women eligible for testing underwent BRCA1/2 gene
      sequencing, 3 declined. 26 (22%) of the 116 women had an alteration in BRCA1/2.
      Known deleterious mutations were present in 3 (3%), uncertain significance
      mutations in 19 (16%), and probable polymorphisms in 6 (5%). There does not
      appear to be a difference in initial biomarker distribution between participants
      with and without germ line alterations.

PMID- 10882859
TI  - Genetics of hereditary colon cancer - a basis for prevention?
AB  - Hereditary colorectal cancer syndromes are among the best in vivo models to study
      colorectal carcinogenesis and the influence of putative modifiers of the cancer
      risk. The present knowledge regarding the wide range of colorectal cancer (CRC)
      susceptibilities and the histological and molecular changes they elicit is
      leading to a very dynamic and integrated concept of tumorigenesis in the colon
      and to new views about prevention and early treatment of cancer.

PMID- 10882860
TI  - Insulin-like growth factor physiology and cancer risk.
AB  - In the past few years, both laboratory investigations and population studies have
      provided strong circumstantial evidence that insulin-like growth factor (IGF)
      physiology influences cancer risk. In contrast to the influence of germ line
      mutations that are rare but are associated with very high risks, the impact of
      inter-individual variability in IGF physiology on risk appears to be modest but
      to effect a relatively high percentage of the population. Although this field of
      investigation is young, attention is already being given to the possibility that
      it may be relevant to clinical assessment of risk and/or to the identification of
      novel prevention strategies and intermediate endpoints. This review summarises
      key results in this field and provides a hypothesis concerning the mechanism by
      which IGF physiology influences risk of common epithelial cancers including those
      of breast, prostate, lung and colon.

PMID- 10882861
TI  - New DNA-based biomarkers for oxidative stress and cancer chemoprevention studies.
AB  - Etheno (epsilon) modified DNA bases (epsilond A, epsilond C, epsilond G) are
      generated from the carcinogens vinyl chloride and urethane, but also by reactions
      of DNA with products derived from lipid peroxidation (LPO) and oxidative stress
      via endogenous pathways. Recently developed ultrasensitive methods allowed the
      detection of these epsilon-adducts in vivo and their role to be studied in
      experimental and human carcinogenesis. Highly variable background levels of
      epsilon-adducts were detected in DNA from different organs of unexposed humans
      and rodents. Several known cancer risk factors increased the level of these DNA
      lesions in target organs: elevated epsilon-adducts were found in hepatic DNA from
      patients with metal storage diseases, after overproduction of nitric oxide (NO)
      by inducible NO synthase (iNOS) in a mouse model, and in colonic polyps of
      familial adenomatous polyposis patients. A high omega-6-polyunsaturated fatty
      acid diet increased epsilon-DNA adducts in white blood cells of female subjects.
      In conclusion, epsilon-adducts were found to be elevated in cancer-prone tissues,
      suggesting that these promutagenic lesions could drive cells to malignancy.
      Therefore, exocyclic DNA adducts offer new tools in cancer aetiological research
      and in verifying the efficacy of chemopreventive agents.

PMID- 10882862
TI  - The antioxidant/anticancer potential of phenolic compounds isolated from olive
      oil.
AB  - In our ongoing studies on the chemoprevention of cancer we have a particular
      interest in the health benefits of the Mediterranean diet, of which olive oil is
      a major component. Recent studies have shown that extravirgin olive oil contains
      an abundance of phenolic antioxidants including simple phenols (hydroxytyrosol,
      tyrosol), aldehydic secoiridoids, flavonoids and lignans (acetoxypinoresinol,
      pinoresinol). All of these phenolic substances are potent inhibitors of reactive
      oxygen species attack on, e.g. salicylic acid, 2-deoxyguanosine. Currently there
      is growing evidence that reactive oxygen species are involved in the aetiology of
      fat-related neoplasms such as cancer of the breast and colorectum. A plausible
      mechanism is a high intake of omega-6 polyunsaturated fatty acids which are
      especially prone to lipid peroxidation initiated and propagated by reactive
      oxygen species, leading to the formation (via alpha,beta-unsaturated aldehydes
      such as trans-4-hydroxy-2-nonenal) of highly pro-mutagenic exocyclic DNA adducts.
      Previous studies have shown that the colonic mucosa of cancer patients and those
      suffering from predisposing inflammatory conditions such as ulcerative colitis
      and Crohn's disease generates appreciably higher quantities of reactive oxygen
      species compared with normal tissue. We have extended these studies by developing
      accurate high performance liquid chromatography (HPLC) methods for the
      quantitation of reactive oxygen species generated by the faecal matrix. The data
      shows that the faecal matrix supports the generation of reactive oxygen species
      in abundance. As yet, there is a dearth of evidence linking this capacity to
      actual components of the diet which may influence the colorectal milieu. However,
      using the newly developed methodology we can demonstrate that the antioxidant
      phenolic compounds present in olive oil are potent inhibitors of free radical
      generation by the faecal matrix. This indicates that the study of the inter
      relation between reactive oxygen species and dietary antioxidants is an area of
      great promise for elucidating mechanisms of colorectal carcinogenesis and
      possible future chemopreventive strategies.

PMID- 10882863
TI  - 'Accidental' anti-angiogenic drugs. anti-oncogene directed signal transduction
      inhibitors and conventional chemotherapeutic agents as examples.
AB  - A number of drugs currently being tested in clinical trials as possible
      angiogenesis inhibitors were not originally developed with the intention of
      suppressing tumour angiogenesis. Thalidomide and interferon alpha are obvious
      examples of such drugs. This list of 'accidental' angiogenesis inhibitors may
      include established agents such as conventional cytotoxic chemotherapeutic drugs
      as well as the new generation of anticancer drugs known as anti-oncoprotein
      signal transduction inhibitors. With respect to the former, the potential of such
      drugs to inhibit angiogenesis could be the result of their ability to cause
      collateral damaging effects on cycling endothelial cells found in newly formed
      blood vessels, or inhibiting other vital endothelial cell functions necessary for
      angiogenesis. The antitumour vascular side-effects of chemotherapy may be
      optimised by administering such drugs continuously on a more frequent (e.g.
      weekly or even daily) basis at levels well below the maximum tolerated dose
      (MTD), especially when this is done in combination with newly developed anti
      angiogenic drugs such as vascular endothelial cell growth factor (VEGF) receptor
      blocking antibodies. This strategy may minimise or delay the problems of host
      toxicity and acquired drug resistance. The possibility of anti-angiogenic effects
      mediated by signal transduction inhibitors such as ras farnesyltransferase
      inhibitors (ras FTI's), or drugs which block receptor tyrosine kinases (e.g.
      ErbB2/neu) such as Herceptin, may be the consequence of such oncogenes inducing
      or upregulating various pro-angiogenic molecules such as VEGF (vascular
      endothelial cell growth factor) in tumour cells. Hence, treatment of tumour cells
      with such drugs can lead to downregulation of tumour cell-associated VEGF
      expression and this can contribute to an anti-angiogenic effect of the drug in
      vivo. In addition, some of these drugs may also affect certain 'activated'
      endothelial cell functions directly so as to block angiogenesis. An awareness of
      the potential of such conventional or experimental anticancer drugs to affect
      tumour growth through blockade or suppression of angiogenesis has implications
      for how anticancer drugs may be used clinically, either alone, or in combination
      with other drugs to optimally treat cancer.

PMID- 10882864
TI  - Interactions between tumour cells and stromal cells and proteolytic modification
      of the extracellular matrix by metalloproteinases in cancer.
AB  - Over the last few years a growing number of matrix degrading metalloproteinases
      have been implicated in cancer. These include in particular the matrix
      metalloproteinases (MMPs) which have been shown to be associated with a large
      variety of human malignancies, and the metalloproteinases with a disintegrin
      domain (ADAMs) whose potential role in cancer has begun to be examined. The
      expression of MMPs in human cancer is the result of a complex interaction between
      tumour cells and non-malignant stromal cells including fibroblasts, endothelial
      cells and inflammatory cells which all actively participate in the production of
      MMPs in tumour tissue. The proteolytic modification of the extracellular matrix
      by these proteases does more than allow malignant cells to locally invade and
      form distant metastasis. It significantly alters the tumour micro-environment and
      modifies the contacts between tumour cells and extracellular matrix proteins.
      These changes can affect essential cellular functions such as growth, survival,
      migration and even drug resistance. As our understanding of the nature of the
      contacts between tumour cells and a proteolytically modified extracellular matrix
      continues to progress, it is likely that novel therapeutic approaches to modify
      tumour cell behaviour will be identified.

PMID- 10882866
TI  - Experimental basis for the prevention of breast cancer.
AB  - Cancer chemoprevention involves intervention in the carcinogenic process by a
      natural or synthetic chemical that either blocks neoplasia development or arrests
      malignant phenotype progression. The chemopreventive test agent must
      experimentally be established as safe before a clinical trial. In our laboratory,
      inhibition of carcinogen-induced development of precancerous lesions in the mouse
      mammary gland organ culture model is used as a primary screen to select
      chemopreventive agents for in vivo efficacy evaluation. A nearly 75% correlation
      apparently exists between the efficacy observed in vitro and in vivo
      carcinogenesis. For in vivo experiments, MNU- and DMBA-induced mammary tumours in
      rats are the models of choice. Numerous agents have been identified and
      progressed to preclinical toxicity and clinical trials. More recently,
      combination chemoprevention has received considerable attention, since no known
      chemopreventive agent sufficiently reduces tumour incidence in rats. The sequence
      of events for establishing the experimental basis for chemoprevention of breast
      cancer is described.

PMID- 10882865
TI  - Rho family proteins in cell adhesion and cell migration.
AB  - Cell migration and the regulation of cadherin-mediated homotypic cell-cell
      interactions are critical events during development, morphogenesis and wound
      healing. Aberrations in signalling pathways involved in the regulation of cell
      migration and cadherin-mediated cell-cell adhesion contribute to tumour invasion
      and metastasis. The rho family proteins, including cdc42, rac1 and rhoA, regulate
      signalling pathways that mediate the distinct actin cytoskeleton changes required
      for both cellular motility and cell-cell adhesion. Recent studies indicate that
      rac directly influences rho activity at the GTPase level and that the reciprocal
      balance between rac and rho activity can determine epithelial or mesenchymal cell
      morphology and migratory behaviour of epithelial (tumour) cells.

PMID- 10882867
TI  - Use of risk determinants for different breast cancer prevention strategies.
AB  - Almost all of the factors which are known to be associated with a high risk of
      breast cancer, other than high genetic risk, are associated with increased
      exposure to oestrogens. Thus, therapeutic manoeuvres targeted at oestrogen
      deprivation which have shown value in established breast cancers are attractive
      candidates for breast cancer prevention strategies. It is possible that such
      agents may reduce the incidence of ER-negative as well as ER-positive tumours.
      The potential use of these different drugs is restricted by menopausal status,
      e.g. aromatase inhibitors only after the menopause, and Gonadotropin-releasing
      hormone (GnRH) agonists prior to the menopause. There is a complex interplay
      between the anticipated benefit which may be derived from a respective agent and
      the side-effects associated with it. This article seeks to integrate the
      information from several sources and concludes that the prophylactic strategies
      should differ according to different risk profiles.

PMID- 10882868
TI  - Molecular and clinical risk markers in colon cancer trials.
AB  - Although there is a great deal of information concerning the risk factors for
      colorectal cancer, progress has been slow in determining methods of
      chemoprevention. In part this is because colorectal cancer consists of a series
      of events over 10-15 years or more, which affects only 3-5% of the population.
      Risk markers for use in patient selection are needed to decrease the sample size
      needed. In addition, there is a need to identify intermediate endpoints of
      success to decrease the follow-up time. Clinical markers of risk are a history of
      colorectal adenomas and of inflammatory bowel disease. Molecular markers include
      a number of genetic markers and enzyme polymorphisms.

PMID- 10882869
TI  - The state-of-the-art in chemoprevention of skin cancer.
AB  - The incidence of skin cancer (both melanoma and non-melanoma) continues to grow
      at an alarming rate. Our chemoprevention strategies include the development of
      novel agents evaluated by (1) preclinical mechanistic studies in models of
      ultraviolet (UV) radiation-induced skin carcinogenesis; (2) clinical studies of
      immunohistochemical surrogate endpoint biomarkers in high-risk patients; and (3)
      randomised, placebo-controlled phase I, II and III clinical chemoprevention
      trials. Recent clinical results validate this development model. Molecular
      targets of chemopreventive strategies for melanoma and non-melanoma skin cancers
      include the ras and activator protein-1 (AP-1) signal transduction pathways. A
      transgenic murine melanoma model has been developed for evaluating potential
      agents in vivo. Agents at various stages of study include the green tea catechin
      epigallocatechin gallate (EGCG), the limonene derivative perillyl alcohol, the
      ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO), selenium,
      retinoids and salicylates. New chemopreventive agents that can be used to
      complement sunscreens may result in decreased incidence, morbidity and mortality
      of skin cancer.

PMID- 10882870
TI  - A brief review of the current breast cancer prevention trials and proposals for
      future trials.
AB  - The available results from breast cancer chemoprevention trials are reviewed.
      Four trials using tamoxifen have been performed of which three have reported
      efficacy results. A fifth trial using raloxifene has also been published. The
      largest tamoxifen trial shows approximately a 50% reduction in breast cancer
      incidence in the short term, but the two smaller trials have not found any
      incidence reduction. Greater agreement exists for side-effects - thromboembolic
      disease and endometrial cancers are raised about 2 to 3-fold when tamoxifen is
      used for 5 years. The possible reasons for the discrepancy in breast cancer
      reduction are explored. A review of trial parameters does not clearly explain
      this difference, and a meta-analysis indicates that all results are compatible
      with a 42% reduction in short-term incidence. Several important questions remain
      about the clinical implication of this result, including the effect on mortality,
      the appropriate risk groups for chemoprevention and the long-term effects on
      incidence. Continued follow-up of these trials is crucial for resolving these
      issues.

PMID- 10882871
TI  - Asian studies of cancer chemoprevention: latest clinical results.
AB  - Chemoprevention trials in Asia, including those already completed and those now
      ongoing, are reviewed. Information was mainly collected from Japan, Korea and
      China. Each country features its own characteristics. Cancer chemoprevention
      trials targeting, from various aspects, hepatocellular carcinoma, gastric cancer
      and colon cancer have been, and are now being, conducted in Japan. Japan also has
      a long history of basic carcinogenesis research and carcinogenic research using
      animal experiments. In Korea, ginseng is the main focus of studies of
      chemopreventive agents. A large body of information has been collected and
      prospective studies are also ongoing. In China, the Linxian study, a cooperative
      study participated in by China and the NCI of the USA, is well known and the
      results impressive. However, we must exercise caution because, for example, the
      population of Linxian are chronically deficient in multiple vitamins and trace
      minerals. This situation may, therefore, differ from that observed in other
      countries. In any event, chemoprevention studies will be popular from an
      economical point of view even in Asia because cancer is becoming the number one
      cause of death in these countries.

PMID- 10882872
TI  - Psychological and sociocultural barriers to cancer genetics and prevention: the
      Asian viewpoint.

PMID- 10882873
TI  - Prostate cancer prevention trials in the USA.
AB  - There is dramatic international variation in prostate cancer mortality rates. The
      variation suggests that the disease has an environmental cause and encourages the
      search for a way to prevent it. Androgenic stimulation over a period of time,
      perhaps due to a high fat diet, has been suggested as a cause of prostate cancer.
      The corollary to this hypothesis is that lowering androgenic stimulation over
      time will prevent prostate cancer. 5-Alpha-reductase inhibition through drugs
      like finasteride have been shown to decrease androgenic stimulation of the
      prostate. A clinical trial is underway using finasteride to assess this
      hypothesis. Epidemiological and laboratory studies also suggest that those with
      high selenium and vitamin E intake have a lower risk of prostate cancer. Recent
      serendipitous findings of two randomised clinical trials support this. A study to
      assess these compounds is currently being designed. Other promising but less
      developed interventions in the chemoprevention of prostate cancer include vitamin
      D supplementation and diet modification.

PMID- 10882874
TI  - Unanswered questions in screening for prostate cancer.
AB  - Prostate cancer fulfils some of the conditions required of a disease that might
      be managed by population screening. In a cohort of 50- to 60-year-old men,
      carrying out a rectal examination and prostate specific antigen (PSA) test will
      detect clinically suspicious areas within the prostate in approximately 5%, and
      approximately 10% will have a raised PSA. We are however unsure which of the
      prostate cancers that are known to be present in approximately 30-40% of men aged
      over 60 years will be detected. Eventually after such screening, around 4% of men
      with an otherwise normal prostate will be found to have prostate cancers. The use
      of rectal examination may increase the number of tumours found, but will reduce
      compliance. The use of free/total PSA ratios will reduce the number of
      unnecessary biopsies at the expense of missing some tumours. Of more concern, we
      remain uncertain how effective aggressive local treatment is in altering the
      natural history of the disease. The risk of a 50-year-old man with a 25 year life
      expectancy of having microscopic cancer is 42%, of having clinically evident
      cancer is 9.5%, and of dying of prostate cancer 2.9%. Only a small proportion of
      cancers known to be present become clinically evident: more men die with prostate
      cancer than of it. Screening will identify some men with cancer who will not
      benefit from treatment. It is unclear whether screening would be followed by a
      reduction in morbidity and mortality. Recent data suggest a screening effect has
      been observed in the USA with: an increase in incidence, a decrease in men with
      distant metastases. The small decrease in mortality recently observed (many times
      smaller than the increase in incidence) may be confounded by inappropriate
      'attribution' of cause of death, the detection of men with better prognosis
      distant metastatic disease responsive to hormonal ablation and changes in social
      factors such as diet. Future changes may incorporate molecular markers that might
      aid identification of men best treated aggressively because of a risk of
      progression. Tests to identify genetic pre-disposition may also allow targeted
      screening. New treatments and early chemoprevention or dietary strategies will
      again shift the ground on which these arguments are being rehearsed. The most
      urgent evidence required concerns the effectiveness of treatment strategies.

PMID- 10882875
TI  - Prostate cancer screening in the Tyrol, Austria: experience and results.
AB  - This article summarises the experience and results of different prostate
      carcinoma screening projects using total prostate specific antigen (PSA) and per
      cent free PSA as the initial test. Of the 21078 volunteers 1618 (8%) had elevated
      PSA levels. Of these men 778 (48%) underwent biopsies; 197 (25%) biopsies were
      positive for prostate carcinoma and 135 (17%) underwent radical prostatectomy. 95
      were found to be organ-confined. A PSA cut-off of 2.5 ng/ml in men aged 45-49
      years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the
      detection rate of organ-confined disease. 284/2272 men (13%) had elevated PSA
      levels and prostate carcinoma was detected in 62 men (3%). All patients underwent
      radical prostatectomy and histological examination revealed organ-confined tumour
      in all but 8 men. 98/340 men (29%) had biopsies positive for carcinoma; 28 of
      these patients (29%) had carcinoma that originated in the transition zone only.
      In the retrospective study, receiver operating characteristic curve analysis
      showed that by using a per cent free PSA of less than 18% as a biopsy criterion,
      37% of the negative biopsies could be eliminated although 94% of all carcinomas
      would still be detected. In the first prospective study, 106/158 men (67%) with
      elevated PSA levels below 10.0 ng/ml were further evaluated and 37 (35%) prostate
      carcinomas were detected. By using a per cent free PSA of <22% as a biopsy
      criterion, 30% of the negative biopsies could be eliminated although 98% of the
      carcinomas would still be detected. In the second prospective study, 120/465 men
      (26%) with total PSA levels between 1.25 and 6.49 ng/ml and a per cent free
      PSA<18% were further evaluated and 27 (23%) were found to have prostate
      carcinomas. Receiver operating characteristic curve analysis for PSA transition
      zone (TZ) density showed that by using a PSA transition zone density of >22
      ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided
      without missing a single carcinoma. In the prescreening era the incidence of T1a
      Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a and T1b Grade 3
      carcinoma was 2.3% whereas in the years after the establishment of PSA-based
      screening the incidence was 4.6 and 1.03% respectively. The rate of organ
      confined tumours increased from 28.7% in 1993 to 65.7% in 1997. In this
      evaluation a new approach, to proceed with a prostate biopsy based upon the
      individual risk of having prostate cancer rather than a single PSA cut-off point
      was developed. High total PSA levels, PSA density and PSA transition zone density
      correlated significantly with high Gleason scores, capsular penetration, a high
      percentage of cancer in the prostatectomy specimen and a high cancer volume. In
      this evaluation all of the 95 patients with PSA levels below 3.99 ng/ml who
      underwent radical prostatectomy showed clinically significant, organ-confined
      prostate cancer with negative surgical margins. The results of this evaluation
      suggest that older men have larger tumour volumes compared with younger men with
      the same PSA levels. These data suggest that PSA-based screening with low PSA cut
      off values increase the detection rate of clinically significant, organ confined
      and potentially curable prostate cancer. Per cent free PSA and PSA transition
      zone density provide an additional diagnostic benefit over total PSA.

PMID- 10882876
TI  - Differences between family physicians and patients in their knowledge and
      attitudes regarding traditional chinese medicine.
AB  - Background: With patients turning more to alternative medicine, most physicians
      are still conservative in their views toward these practices. It is important to
      know whether there is a difference between physicians and patients regarding
      knowledge and attitudes about alternative medicine. This study focused on
      information regarding a specific type of alternative medicine, traditional
      Chinese medicine (TCM). Methods: Two questionnaires-one for physicians, one for
      patients-were designed. Two clinics were chosen as sites where patients could
      fill out the questionnaires while they were waiting for treatment. A total of 85
      patient questionnaires were collected. Forty-four completed questionnaires were
      returned from family physicians in Cincinnati area. Data analyiss included t
      test, analysis of variance, and logistic regression. Results: Generally,
      physicians and patients had the same knowledge level on TCM. Physicians, however,
      had more knowledge on basic concepts, whereas patients knew more about practice,
      such as the specific conditions that could be treated by TCM. A difference
      between physicians and patients on attitudes toward TCM was found, with patients
      having a more positive attitude. More than 60% of the patients in this study had
      visited alternative practitioners during the year prior to this study. The inform
      rate was higher for the patients visiting physicians who practiced alternative
      treatment. Conclusions: There are differences between physicians and patients
      regarding their knowledge and attitudes about TCM.

PMID- 10882877
TI  - Personal and professional beliefs and practices regarding herbal medicine among
      the full time faculty of the newark-based schools of the university of medicine
      and dentistry of new jersey.
AB  - Background: The use of alternative and herbal medicine is increasing among the
      general population in the United States. The use of herbal medicine by health
      care professionals has not been documented. Health care professionals tend to
      base personal and professional practices on scientific research and facts. This
      population interacts with the public and with health care students. Therefore,
      personal and professional practices will impact these audiences. Methods: A
      survey was distributed to all faculty members of the University of Medicine and
      Dentistry of New Jersey via interoffice mail. A total of 904 surveys were sent.
      Statistical analyses included descriptive analysis of personal and professional
      practice regarding herbal medicine and chi(2) analysis of the relationship
      between personal and professional practices regarding herbal medicine.
      Significance was set at alpha <.05. Results: The overall response rate was 51%.
      Approximately one-third (29.6%, n = 134) of the population reported personal use
      of herbal medicine, 22.1% (n = 42) of the population who provide patient care
      recommend herbal medicine, 9.4% (n = 36) of those involved in teaching include
      herbal medicine in coursework, and 1.1% of the population were involved in
      research on herbs. Respondents who use herbal medicine were more likely to
      recommend herbs to patients (p <.0001); likewise, users of herbal medicine were
      more likely to teach students about herbal medicine (p =.001). Conclusions: The
      results support the hypothesis that personal beliefs and practices do impact
      professional practices within the clinical and academic settings of the
      university.

PMID- 10882878
TI  - Changes in heart transplant recipients that parallel the personalities of their
      donors.
AB  - Context: It is generally assumed that learning is restricted to neural and immune
      systems. However, the systemic memory hypothesis predicts that all dynamical
      systems that contain recurrent feedback loops store information and energy to
      various degrees. Sensitive transplant patients may evidence personal changes that
      parallel the history of their donors. Objective: To evaluate whether changes
      following heart transplant surgery parallel the history of the donors. Design:
      Open-ended interviews with volunteer (1) transplant recipients, (2) recipient
      families or friends, and (3) donor families or friends. Setting: Hospitals in
      various parts of the country. Patients: Ten recipients (7 males, 3 females; 7
      months to 56 years old), received heart (or heart-lung) transplants (5 males, 5
      females; 16 months to 34 years old). Main Outcome Measures: Transcripts of audio
      taped interviews quoted verbatim. Results: Two to 5 parallels per case were
      observed between changes following surgery and the histories of the donors.
      Parallels included changes in food, music, art, sexual, recreational, and career
      preferences, as well as specific instances of perceptions of names and sensory
      experiences related to the donors (e.g., one donor was killed by a gun shot to
      the face; the recipient had dreams of seeing hot flashes of light in his face).
      Conclusion: The incidence of recipient awareness of personal changes in cardiac
      transplant patients is unknown. The effects of the immunosuppressant drugs,
      stress of the surgery, and statistical coincidence are likely insufficient to
      explain the findings. The plausibility of cellular memory, possibly systemic
      memory, is suggested.

PMID- 10882879
TI  - Pine bark extract reduces platelet aggregation.
AB  - The effects of long-term consumption of the bioflavonoid mixture, French maritime
      pine bark extract (Pycnogenol(R)), were assessed on aggregation of platelets from
      cigarette smokers and nonsmokers. Previously we showed that a single dose of
      Pycnogenol(R) reduced platelet aggregation in cigarette smokers in a dose
      response fashion. Cigarette smoking increased platelet reactivity aggregation
      when measured 2 h after smoking the first cigarette of the day. Blood was
      collected immediately before and 5 min after smoking three cigarettes each.
      Smoking increased platelet aggregation (1.17 +/- 0.04). However 200 mg
      Pycnogenol(R)/day, taken 3 h prior to first cigarette for the day for 2 months,
      significantly (p <.0023) reduced smoke-induced platelet aggregation (0.98 +/-
      0.05) to the level of nonsmokers. In a group of 19 nonsmokers, platelet
      aggregation was measured during in vitro stimulation by platelet aggregation
      factor (PAF) after 4 or 8 weeks of 200 mg/day of Pycnogenol(R) consumption.
      Platelet aggregation was significant when induced in vitro by PAF. However,
      Pycnogenol(R) consumption did not change platelet aggregation, suggesting that
      Pycnogenol(R)'s regulation of aggregation is by another mechanism. Thromboxane A2
      (TxA2) is increased in smokers by release from platelets and rapidly becomes
      thromboxane B2 (TxB2). Smoking increased TxB2, which was prevented by
      Pycnogenol(R), lowering TxB2 levels to those of nonsmokers. However,
      Pycnogenol(R) had no effect on the lower levels of TxB2 in nonsmokers. These
      observations suggest that Pycnogenol(R) supplementation reduces a risk factor for
      cardiovascular diseases, that is, platelet aggregation in smokers. The
      bioflavonoids in Pycnogenol(R) reduced platelet aggregation stimulated by tobacco
      smoke.

PMID- 10882880
TI  - Use of a chinese herbal medicine for treatment of hiv-associated pathogen
      negative diarrhea.
AB  - Background: Diarrhea is a frequent problem among persons with advanced HIV
      disease. In the absence of treatable pathogens, symptomatic relief is all that is
      available for current therapy. As a result, many patients with HIV and chronic
      diarrhea have turned to herbal formulas for treatment. We assessed the
      effectiveness and safety of a Chinese herbal formulation (Source Qi) in reducing
      the number of stools per day related to HIV-associated, pathogen-negative
      diarrhea. Methods: Sixteen male patients received treatment with Source Qi in an
      8-week, open-label study. Patients tested negative for cryptosporidium and other
      gastrointestinal pathogens, and had chronic diarrhea, defined as having three or
      more loose stools/day for >/=14 days (and no other treatable causes for
      diarrhea). Measurements of diarrhea included numbers of bowel movements/day,
      abnormal bowel movements/day, and liquid bowel movements/day. Subjects completed
      daily stool diaries an average of 2 weeks before and up to 8 weeks after starting
      Source Qi. Paired Wilcoxon tests compared the last week before treatment with
      each week of treatment. Results: There was a reduction in average number of
      stools/day in each week of treatment (-0.2 to -0.8), except week 1 (+0.1), with
      improvements in weeks 2-6 approaching or reaching statistical significance.
      Conclusions: A modest but sustained decrease in average number of stools/day was
      observed in patients with HIV-associated, pathogen-negative diarrhea. The entry
      criteria, 2-week run-in period, lack of benefit in week 1, and sustained benefit
      thereafter all suggest that the improvement was not due to bias.

PMID- 10882881
TI  - beta-Carotene and selenium supplementation enhances immune response in aged
      humans.
AB  - Background: Nutritional research has focused on the effects of specific
      nutrients' ability to cause or prevent cancer. While beta-carotene and selenium
      (both important for antioxidant systems) have cancer prevention capabilities,
      their antineoplastic mechanism(s) remains to be elucidated. Methods: In a
      prospective, randomized study design we evaluated immunological changes in free
      living, healthy aged humans (57-84 years of age) given a placebo, beta-carotene
      (45 mg/day), and/or selenium (400 ug/day) supplement for 6 months and after 2
      months of discontinuation. Peripheral blood lymphocytes were evaluated and
      subtyped using flowcytometry. Natural killer (NK) cell cytotoxicity was
      determined by a fluorescent method. Plasma diene conjugates were assessed to
      evaluate changes in oxidative stress. Results: Selenium and selenium plus beta
      carotene supplementation caused an increase in total T cells by 27% and 31%,
      respectively (p <.05). The only group that was different (in T lymphocytes) from
      the controls (placebo group) after 6 months of supplementation (p <.05) was the
      selenium-supplemented group (+65%). Much of this increase was the result of an
      increase in CD4(+) T-cell subsets. Selenium or beta-carotene supplementation for
      3 months increased NK cell cytotoxicity over pretreatment levels by 58% and 34%,
      respectively; however, these levels returned to +12% and -6% of pretreatment
      levels after 6 months supplementation. Selenium plus beta-carotene
      supplementation caused an increase in the percentage of NK cell by 121% and 161%
      at 3 and 6 months, respectively. However, the increased numbers of NK cells were
      not correlated with NK cell activity. Conclusions: We found that selenium
      enhanced immune function (NK cell cytotoxicity) and phenotypic expression of T
      cell subsets, whereas beta-carotene affected only immune function. Increased NK
      cell cytotoxicity may last for only a short period of supplementation and was not
      sustained throughout the 6 months of supplementation. Supplemental selenium and
      beta-carotene seemed to affect immune function in aged subjects by different
      mechanisms.

PMID- 10882882
TI  - Can children with spastic cerebral palsy use self-hypnosis to reduce muscle tone?
      a preliminary study.
AB  - A few scattered reports suggest self-hypnosis may be helpful in reducing muscle
      tone in children with spastic cerebral palsy (CP). These reports are largely
      anecdotal and offer little objective evidence. This study used the Biocomp 2000
      biofeedback electomyogram device to measure the degree of muscle tension in two
      muscle groups before, during, and after hypnosis in four children with spastic
      quadriplegic CP. Three of the four children were able to show a very significant
      decrease in muscle tension while under "trance" and were able to use self
      relaxation techniques when confronted with stressful situations. Two of the
      children also had athetoid or involuntary movements and each was able to better
      control those movements with the aid of hypnosis. All four children demonstrated
      improved functional abilities.

PMID- 10882883
TI  - Use of alternative treatments by chronic fatigue syndrome discordant twins.
AB  - Background: Patients with chronic fatigue syndrome (CFS) have been faced with
      difficulties in diagnosis and lack of effective treatments. Anecdotal evidence
      suggests that use of alternative treatments may be common in these patients. Our
      primary objective was to compare the prevalence and patterns of alternative
      medicine use among twins who met the Centers for Disease Control and Prevention
      (CDC) CFS criteria to that of their non-CFS co-twins. Secondary goals were to
      assess how often alternative medicine use was discussed with physicians and the
      perceived benefit of these therapies. Methods: Sixty-three twin pairs discordant
      for CFS completed a survey about their use of 22 alternative therapies. Matched
      pair odds ratios and 95% confidence intervals were used to examine differences in
      the use between CFS twins and their non-CFS co-twins. Results: 91% of twins with
      CFS and 71% of non-CFS twins had used at least 1 alternative treatment in their
      lifetime. Twins with CFS were more likely to use homeopathy, mega-vitamins,
      herbal therapies, biofeedback, relaxation/meditation, guided imagery, massage
      therapy, energy healing, religious healing by others, and self-help groups than
      their non-CFS counterparts. A large proportion of all twins found alternative
      therapies helpful; however, only 42% of those with CFS and 23% of those without
      CFS discussed their use of alternative medicine with a physician. Conclusions:
      Individuals with CFS frequently used alternative medical treatments yet rarely
      communicated this use to their medical doctor. Future research should ascertain
      the usefulness of alternative practices in the management of CFS.

PMID- 10882884
TI  - Systemic aspects of psoriasis. An integrative model based on intestinal etiology.
AB  - Psoriasis can best be understood from a multifactorial approach that recognizes
      the systemic aspects of the disorder. Among the various factors thought to be
      involved in the etiology and pathogenesis of psoriasis, bowel pathology has
      assumed a noteworthy position in the literature. This article reviews the
      psoriasis/bowel connection with regard to abnormal bowel structure and physiology
      in psoriasis patients. Clinical implications of bowel involvement in psoriasis
      are discussed within the framework of an integrative medicine model that
      emphasizes natural therapeutics for addressing the systemic aspects of the
      illness.

PMID- 10882885
TI  - Uses of guided imagery for pain control by african-american and white women with
      metastatic breast cancer.
AB  - Understanding the meanings patients attach to their experiences can help
      clinicians and researchers to more adequately address a patient's experience with
      cancer pain. Indeed, many patients seem to desire to and benefit from attaching
      meaning to the disease and its treatment. In particular, many patients are drawn
      to guided imagery as a tool in the management of cancer-related anxiety and pain.
      Using excerpts from African-American and White women's breast cancer narratives,
      we show that breast cancer survivors use guided imagery as a vehicle for
      reconnecting to the self, to make sense of their experiences with breast cancer,
      and as a tool for managing cancer pain. Cancer pain increases the disruption in
      the connection between the body and the mind that is already part of the illness
      experience. Guided imagery can be regarded as one response to this problem, and
      may be understood as an attempt to reconnect mind and body in a manner that
      increases the sense of control, thereby alleviating the suffering of the
      survivor.

PMID- 10882886
TI  - Hypnotherapy for crohn's disease. A promising complementary/alternative therapy.
AB  - Crohn's disease is a nonspecific chronic syndrome of unknown origin for which, to
      date, no conventional (i.e., medical or surgical) cure exists. However, recent
      clinical case studies and anecdotal reports have shown that the use of different
      forms of hypnotherapy for the treatment of Crohn's have actually resulted in
      cures. This report reviews and compares the effectiveness of hypnotherapy in the
      treatment of Crohn's disease vis-a-vis current medical and surgical therapies, in
      addition to reviewing evidence of the modulation of immune function parameters by
      hypnosis, while providing support for current etiological hypotheses of Crohn's
      disease as an autoimmune disorder.

PMID- 10882887
TI  - Exploring the role of progestins and phytoestrogens in menopause.

PMID- 10882889
TI  - Cytogenetic effect of the anticancer drug epirubicin on Chinese hamster cell line
      in vitro.
AB  - The present study demonstrated the cytogenetic effect of the anticancer drug
      epirubicin on cultures of Chinese hamster cell line in vitro. The cultures were
      exposed to the drug for 24 h at three final concentrations; 10, 20 and 40
      microg/ml. All treatments were carried out in the absence of any exogenous
      metabolic activation system. The different types of structural chromosomal
      aberrations, including gaps, breaks, deletions and fragments were increased in
      epirubicin-treated cultures. This increase was dose dependent where there was a
      positive correlation between increased drug concentration and induction of
      structural chromosomal aberrations. Also, the numerical chromosomal aberrations,
      including hypodiploidy and hyperdiploidy, were increased significantly in
      epirubicin-treated cultures. Like structural aberrations, the increase of
      numerical chromosomal aberrations was also dose-dependent. The frequency of
      sister chromatid exchanges in cultures treated with epirubicin increased
      significantly and this increase was dose-dependent. On the other hand, the
      epirubicin significantly decreased the mitotic index in treated cultures of
      Chinese hamster cell line.

PMID- 10882888
TI  - Validation of single cell gel assay in human leukocytes with 18 reference
      compounds.
AB  - To validate the alkaline single cell gel (SCG) assay as a tool for the detection
      of DNA damage in human leukocytes, we investigated the in vitro activity of 18
      chemicals. Thirteen of these chemicals (pyrene (PY), benzo(a)pyrene (BaP),
      cyclophosphamide (CP), 4-nitroquinoline-1-oxide (4NQO), bleomycin (BLM),
      methylmercury chloride (MMC), mitomycin C (MTC), hydrogen peroxide (HP),
      diepoxybutane (DEB), glutaraldehyde (GA), formaldehyde (FA), griseofulvin (GF),
      sodium azide (NA)) are genotoxic in at least one cell system, while five
      compounds (ascorbic acid (AA), glucose (GL), D-mannitol (MAN), O-vanillin (VAN),
      chlorophyllin (CHL)) are classified as non-genotoxic. In this in vitro SCG assay,
      PY, BaP and CP were positive with exogeneous metabolic activation (rat S9 mix)
      while 4NQO, BLM, MMC, MTC, hydrogen peroxide, and diepoxbutane were positive in
      the absence of metabolic activation. CHL and VAN were unexpectedly found to
      induce a dose-dependent increase in DNA migration. AA, GL, and MAN were negative
      in a non-toxic range of doses. GF gave equivocal results, while FA and GA
      increased DNA migration at low doses and decreased DNA migration at higher doses.
      This behaviour is consistent with the known DNA damaging and crosslinking
      properties of these compounds. These data support the sensitivity and specificity
      of this assay for identifying genotoxic agents.

PMID- 10882890
TI  - A strong genotoxic effect in mouse skin of a single painting of coal tar in
      hairless mice and in MutaMouse.
AB  - The dorsal skin of C3H/Tif/hr hairless mice was painted with coal tar,
      pharmacological grade. Epidermal cells and hepatocytes were isolated after 4, 24,
      48 and 96 h and DNA strand breaks were determined as tail moment by the alkaline
      comet assay. The tail moment of epidermal cells was significantly greater at the
      time points 4, 24, 48 and 96 h after exposure compared to the controls, with the
      most DNA strand breaks at 24 h. The DNA strand breaks in epidermal cells
      increased linearly with the dose of coal tar. In hepatocytes, no difference in
      DNA strand breaks was found between exposed animals and controls. DNA adducts
      were determined by the 32P-postlabeling assay. For epidermal cells, the mean DNA
      adduct level was 12-fold greater in coal tar painted mice after 24 h than in
      controls. Again, a linear dose/response relationship was seen 24 h after
      painting. For liver DNA, the mean DNA adduct level was 3-fold greater than for
      controls. The mutation frequency in epidermal and liver cells was examined in
      lambdalacZ transgenic mice (MutaMouse). Thirty-two days after painting, the
      mutation frequency in epidermal cells was 16-fold greater in coal tar treated
      mice compared to controls. No effect was detected in hepatocytes. We found that a
      single painting of coal tar resulted in strong genotoxic effects in the murine
      epidermis, evidenced by induction of DNA strand breaks and DNA adducts in
      hairless mice and lambdalacZ mutations in the MutaMouse. This demonstrates that
      it is possible to detect genotoxic effects of mixtures with high sensitivity in
      mouse skin by these end-points.

PMID- 10882891
TI  - Immunoperoxidase detection of 4-aminobiphenyl- and polycyclic aromatic
      hydrocarbons-DNA adducts in induced sputum of smokers and non-smokers.
AB  - Tobacco smoke constituents, 4-aminobiphenyl (4-ABP) and polycyclic aromatic
      hydrocarbons (PAH) possess carcinogenic properties as their reactive metabolites
      form DNA adducts. We studied the formation of 4-ABP- and PAH-DNA adducts in
      induced sputum, a non-invasively obtainable matrix from the lower respiratory
      tract, of smokers (n=20) and non-smokers (n=24) utilizing a semi-quantitative
      immunohistochemical peroxidase assay. Smokers had significantly higher levels of
      4-ABP-DNA adducts as compared to non-smokers (0. 08+/-0.02 versus 0.04+/-0.01,
      P=0.001, density of immunohistochemical staining), and the levels of adducts were
      related to current smoking indices (cigarettes/day: r=0.3, P=0.04 and tar/day:
      r=0.4, P=0.02). Likewise, smokers had elevated levels of PAH-DNA adducts as
      compared to non-smokers, however, the differences was not statistically
      significant (0.13+/-0.02 versus 0. 08+/-0.02, P=0.07). The levels of PAH-DNA
      adducts were only significantly related to the amount of tar consumed per day
      (r=0.4, P=0.04) but not to the number of cigarettes smoked per day. Neither the
      levels of 4-ABP-DNA adducts nor those of PAH-DNA adducts were related to smoking
      history index (pack years). Further, the levels of 4-ABP-DNA adducts were
      correlated with those of PAH-DNA adducts (r=0.4, P=0.02). We conclude that
      immunohistochemistry of 4-ABP-DNA adducts in induced sputum is a specific
      approach to assess current exposure to tobacco smoke in the lower respiratory
      tract, however, in the case of PAH-DNA adducts, such analysis is less specific as
      it does not explicitly reflect the magnitude of the exposure.

PMID- 10882892
TI  - In vitro micronucleus assay with Chinese hamster V79 cells - results of a
      collaborative study with in situ exposure to 26 chemical substances.
AB  - A collaborative study with 10 participating laboratories was conducted to
      evaluate a test protocol for the performance of the in vitro micronucleus (MN)
      test using the V79 cell line with one treatment and one sampling time only. A
      total of 26 coded substances were tested in this study for MN-inducing
      properties. Three substances were tested by all 10 laboratories and 23 substances
      were tested by three or four laboratories in parallel. Six aneugenic, 7
      clastogenic and 6 non-genotoxic chemicals were uniformly recognised as such by
      all laboratories. Three chemicals were tested uniformly negative by three
      laboratories although also clastogenic properties have been reported for these
      substances. Another set of three clastogenic substances showed inconsistent
      results and one non-clastogenic substance was found to be positive by one out of
      three laboratories. Within the study, the applicability of the determination of a
      proliferation index (PI) as an internal cytotoxicity parameter in comparison with
      the determination of the mitotic index (MI) was also evaluated. Both parameters
      were found to be useful for the interpretation of the MN test result with regard
      to the control of cell cycle kinetics and the mode of action for MN induction.
      The MN test in vitro was found to be easy to perform and its results were mainly
      in accordance with results from chromosomal aberration tests in vitro.

PMID- 10882893
TI  - Mutagenic profile of rubber dust and fume exposure in two rubber tire companies.
AB  - The aim of this study was to evaluate current mutagenic activity of ambient
      rubber dust and fume exposure in the mixing and curing departments of two rubber
      tire companies situated in The Netherlands and Sweden. Salmonella typhimurium
      strains YG1021, YG1024 and YG1041 were used to study the possible presence of
      mutagenic nitroarenes and aromatic amines. A large difference in mutagenic
      activity was found between the two companies. While the rubber tire company
      situated in The Netherlands revealed overall high mutagenic activity of rubber
      dust and fumes in the mixing and curing departments, respectively, 430 and 279
      rev/m(3) (YG1041), the Swedish company showed almost no mutagenic activity,
      respectively, 18 and 54 rev/m(3) (YG1041). Further identification of the
      mutagenic profile showed that mutagenic activity was exclusively observed in S.
      typhimurium strains with elevated levels of O-acetyltransferase activity (YG1041
      and YG1024) in the presence of a metabolic active liver S9 fraction, possibly
      indicating the presence of indirect mutagenic aromatic amines. These results show
      that although production processes and lay-out within rubber tire companies are
      comparable, differences in rubber chemicals used and overall level of control
      measures (e.g., good housekeeping, cleanliness) are likely to result in
      substantial differences in mutagenic exposure levels between companies.

PMID- 10882894
TI  - Methylglyoxal induces G:C to C:G and G:C to T:A transversions in the supF gene on
      a shuttle vector plasmid replicated in mammalian cells.
AB  - We previously reported that the majority of base-pair substitutions induced by an
      endogenous mutagen, methylglyoxal, were G:C-->T:A transversions and G:C-->A:T
      transitions in wild-type and nucleotide excision repair (NER)-deficient (uvrA or
      uvrC) Escherichia coli strains. To investigate the mutation spectrum of
      methylglyoxal in mammalian cells and to compare the spectrum with those detected
      in other experimental systems, we analyzed mutations in a bacterial suppressor
      tRNA (supF) gene in the shuttle vector plasmid pMY189. We treated pMY189 with
      methylglyoxal and immediately transfected it into simian COS-7 cells. The
      cytotoxicity and the mutation frequency (MF) increased according to the dose of
      methylglyoxal. In the mutants induced by methylglyoxal, multi-base deletions were
      predominant (50%), followed by base-pair substitutions (35%), in which 89% of the
      substitutions occurred at G:C sites. Among them, G:C-->C:G and G:C-->T:A
      transversions were predominant. The overall distribution of methylglyoxal-induced
      mutations detected in the supF gene was different from that for the spontaneous
      mutations. These results suggest that methylglyoxal may take part in causing G:C-
      >C:G and G:C-->T:A transversions in vivo.

PMID- 10882895
TI  - Antimutagenic profile of three antioxidants in the Ames assay and the Drosophila
      wing spot test.
AB  - Antimutagens and anticarcinogens are known to play an important role in combating
      the action of factors involved in the etiology of cancer. It is expected that
      inhibitors of mutagenesis also act as inhibitors of carcinogenesis. In the
      present study, two short-term genotoxicity assays, namely the Ames assay and the
      Drosophila wing spot test, have been selected for examining the antimutagenic
      potential of three antioxidants. For this purpose, a promutagen aflatoxin B(1)
      (AFB(1)) was chosen as a positive mutagen against which antimutagenic potential
      of alpha-tocopherol (Vit. E), caffeic acid (CA) and glutathione (GSH) was
      assessed. Vit. E did not exert any antimutagenic response while CA and GSH were
      effective in reducing the mutational events induced by AFB(1).

PMID- 10882896
TI  - Levels of 8-hydroxy-2'-deoxyguanosine in DNA of white blood cells from workers
      highly exposed to asbestos in Germany.
AB  - Asbestos fibers have genotoxic effects and are a potential carcinogenic hazard to
      occupationally exposed workers. The ability of inhaled asbestos fibers to induce
      the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the DNA of white blood
      cells (WBC) of workers highly exposed at the workplace has been studied. The 8
      OHdG adduct level of asbestos-exposed workers was significantly increased
      (p<0.001) compared to that in the control group in all three years of the study.
      Asbestos-exposed individuals showed a mean value of 2.61+/-0.91 8-OHdG/10(5) dG
      (median 2.49, n=496) in 1994-1995, 2.96+/-1.10 8-OHdG/10(5) dG (median 2.76,
      n=437) in 1995-1996 and 2.55+/-0.56 8-OHdG/10(5) dG (median 2.53, n=447) in 1996
      1997. For the control subjects, a mean of 1.52+/-0.39 (median 1.51, n=214) was
      determined. The results indicate that human DNA samples from exposed individuals
      contain between 1.7 times and twice the level of oxidative damage relative to
      that found in control samples in all 3 years of the study. The studies presented
      here show that asbestos exposure can result in oxidative DNA damage. Our data
      confirm that oxidative DNA damage occurs in the WBC of workers highly exposed to
      asbestos fibers, thus supporting the hypothesis that asbestos fibers damage cells
      through an oxidative mechanism. These in vivo findings underline the importance
      of oxidative damage in asbestos-induced carcinogenesis and highlight the need for
      exploring the molecular basis of asbestos-induced diseases, and for more
      effective diagnosis, prevention and therapy of mesothelioma, lung cancer and
      pulmonary fibrosis. In addition, preventive and therapeutic approaches using
      antioxidants may be relevant.

PMID- 10882898
TI  - Evaluation of the single cell gel electrophoresis assay with human hepatoma (Hep
      G2) cells.
AB  - Human Hep G2 cells have retained the activities of phase I and phase II enzymes
      which are involved in the metabolism of environmental genotoxins. The present
      study describes the results of single cell gel electrophoresis (SCGE) assays with
      a panel of different model compounds with these cells. With genotoxic carcinogens
      such as aflatoxin B(1) (AFB(1)), benzo(a)pyrene (B(a)P), nitrosodimethylamine
      (NDMA) and cyclophosphamide (CP), statistically significant dose dependent
      induction of DNA migration was measured. With the two heterocyclic amines, 2
      amino-3-methyl-3H-imidazo[4, 5-f]quinoline (IQ) and 3-amino-1,4-dimethyl-5H
      pyrido[4,3-b]indole (Trp-P-1), and also with rodent carcinogens such as safrole,
      hexamethylphosphoramide (HMPA) and the pyrrolizidine alkaloid isatidine, which
      give negative results in other in vitro genotoxicity tests, positive results were
      obtained in Hep G2/SCGE assays. Nitrosomethylurea (NMU) was the only directly
      acting compound tested in the study and was by far (ca. 10(3)-fold) more active
      than the corresponding nitrosamine. The exposure concentrations required to cause
      significant effects varied over a broad range. The most pronounced effect was
      seen with AFB(1) (0.008 microM) followed by HMPA (15 microM), B(a)P (25 microM),
      NMU (100 microM), isatidin (500 microM), CP (900 microM), IQ (1200 microM),
      safrol (4000 microM), and NDMA (90x10(3) microM). Numbers in parenthesis give the
      lowest concentrations, which caused a significant increase of DNA migration. With
      two compounds, namely, the non-carcinogen pyrene and the synthetic hormone
      tamoxifen (TF), negative results were obtained under all test conditions. These
      findings are in agreement with the results of recent investigations which
      indicated that human hepatocytes are unable to convert TF to DNA reactive
      metabolites, whereas it is activated by rat liver cells and causes DNA adducts in
      these cells. Comparisons of the present results with data from earlier
      experiments indicate that the Hep G2/SCGE assay enables the detection of
      genotoxins including compounds which give misleading results in other in vitro
      genotoxicity tests and appears to be an alternative to tests with primary liver
      cells from laboratory animals.

PMID- 10882897
TI  - Association between 8-hydroxy-2'-deoxyguanosine levels in DNA of workers highly
      exposed to asbestos and their clinical data, occupational and non-occupational
      confounding factors, and cancer.
AB  - In the preceding paper [B. Marczynski, P. Rozynek, T. Kraus, St. Schlosser, H.J.
      Raithel, X. Baur, Levels of 8-hydroxy-2'-deoxyguanosine in DNA of white blood
      cells from workers highly exposed to asbestos in Germany, Mutat. Res. (2000)
      submitted] we described significant increases (p<0.001) in the levels of 8
      hydroxy-2'-deoxyguanosine (8-OHdG) adducts in the DNA of white blood cells (WBC)
      of workers highly exposed to asbestos fibers at the workplace relative to those
      found in the control group in all three study years (period between 1994 and
      1997). The results show that the oxidative DNA damage in exposed individuals is
      between 1.7 times and twice that found in control samples for all 3 years of the
      study (p<0.001). The aim of this study was to examine the association between the
      8-OHdG levels in WBC DNA of workers highly exposed to asbestos fibers at the
      workplace and clinical data, occupational and non-occupational confounding
      factors, and cancer. There is no obvious correlation between the steady-state
      levels of 8-OHdG in the circulating WBC DNA of asbestos workers and possible
      confounding factors, such as the presence of benign asbestos-associated diseases,
      the duration of asbestos exposure, the latency period, the fixed cumulative
      fibrous dust dose ("fiber years"), age, smoking status, acute febrile infections,
      medicines, aspirin, calcium (Ca(2+)), magnesium (Mg(2+)), and the hormone and
      vitamin intake. This indicates that previous inhalation of asbestos fibers is the
      major factor responsible for the difference observed in oxidative DNA damage
      between asbestos workers and controls. For patients suffering from respiratory
      cancer, cancer of the gastrointestinal tract, mouth/pharynx/larynx, and
      urogenital tract the mean DNA-adduct level was significantly higher (p<0.01) than
      that found in controls, but not significantly higher (p>0.05) than that for
      asbestos-exposed patients without tumours. The formation of 8-OHdG adduct levels
      in WBC DNA of patients with hematopoietic cancer, chondrosarcomas and multiform
      glioblastomas was not significantly higher than that found in the control group
      (p>0.05). Our results support the hypothesis that oxidative DNA damage in man
      caused by asbestos fibers plays a role in the formation of malignant tumours.

PMID- 10882899
TI  - In vitro detection of indirect-acting genotoxins in the comet assay using Hep G2
      cells.
AB  - The induction of DNA damage by four known promutagens (cyclophosphamide (CP),
      benzo(a)pyrene (BP), dimethylbenz(a)anthracene and 2-acetylaminofluorene (2AAF)
      was investigated on Hep G2 using the alkaline single cell electroporesis (SCGE)
      test, most often referred as the "comet assay". After a 3-day incubation, lysed
      cells embedded in agarose were electrophoresed under alkaline conditions, dyed
      with a SYBRgold fluorogen and analysed by the Komet software. Among the comet
      parameters provided by the image analysis program, statistical analysis did not
      identify any in particular that could best represent the DNA damages. All
      promutagens, when compared with the control, caused a statistically significant
      increase in DNA migration as determined by different parameters such as Olive
      tail moment, tail extent moment, tail/head or tail length. The data demonstrated
      the ability and the sensitivity of the comet assay when performed on Hep G2 in
      the detection of DNA damage induced by promutagens, and its suitability in
      mutagenicity testing in in vitro short-term assays.

PMID- 10882900
TI  - Serine repeat antigen peptides which bind specifically to red blood cells.
AB  - It has been reported that serine repeat antigen (SERA) binds directly to human
      erythrocyte membranes, inside-out vesicles and intact mouse erythrocytes.
      Similarly, mAbs specific against SERA are effective in blocking red blood cell
      (RBC) invasion by P. falciparum merozoites. Furthermore, the N-terminal
      recombinant SERA fragment inhibits the merozoite invasion of erythrocyte. In this
      study of 49 non-overlapping 20-residue-long peptides encompassing the whole SERA
      protein FCR3 strain, seven peptides having high RBC binding activity were found.
      Six of these peptides (three from the SERA N-terminal domain) are located in
      conserved regions and show affinity constants between 150 and 1100 nM, Hill
      coefficients between 1.5 and 3.0 and 30000-120000 binding sites per cell. Some of
      these peptides inhibited in vitro merozoite invasion of erythrocyte and intra
      erythrocytic development. Residues which are critical in the binding to
      erythrocytes (in bold face), i.e. 6725 (YLKETNNAISFESNSGSLEKK), 6733
      (YALGSDIPEKCDTLASNCFLS), 6737 (YDNILVKMFKTNENNDKSELI), 6746
      (DQGNCDTSWIFASKYHLETI), 6754 (YKKVQNLCGDDTADHAVNIVG) and 6762
      (NEVSERVHVYHILKHIKDGK), were determined by means of competition assays with high
      binding peptide glycine analogues. The identification of peptides which bind to
      erythrocyte membrane is important in understanding the process of RBC invasion by
      P. falciparum merozoites.

PMID- 10882901
TI  - Differential intra-epithelial lymphocyte phenotypes following Cryptosporidium
      parvum challenge in susceptible and resistant athymic strains of mice.
AB  - The lack of immunocompetent laboratory animal models has limited our
      understanding of functional immune responses to Cryptosporidium parvum infection,
      but such responses have been studied in susceptible laboratory rodents with
      genetic, acquired, or induced immunodeficiencies. We previously observed that
      athymic C57BL/6J nude mice inoculated with C. parvum oocysts had lower or absent
      fecal oocyst excretion when compared to inoculated athymic BALB/cJ nude mice.
      This discrepancy prompted us to explore potential differences in intestinal
      immune responses in both strains. Prior to and after C. parvum challenge, BALB/cJ
      nude and C57BL/6J nude mice did not differ in either spleen cell numbers or in
      parasite-specific proliferation. However, both strains of mice exhibited a
      significant increase in intra-epithelial lymphocyte (IEL) numbers prior to and
      following C. parvum inoculation when compared to uninoculated controls (P<0.05).
      Prior to challenge, C57BL/6J nude mice had a higher percentage of both CD8+ and
      CD8+ gammadelta+ IEL than BALB/cJ nude mice. Following challenge, resistant
      C57BL/6J nude mice had a higher percentage of gammadelta+, CD4+, and CD8+
      gammadelta+ IEL than uninoculated C57BL/6J nude mice and than susceptible BALB/cJ
      nude mice (P<0.05). Conversely, inoculated C57BL/6J nude mice had a significantly
      lower percentage of alphabeta+ IEL than inoculated BALB/cJ nude mice (P<0.05). We
      conclude that gammadelta+, CD4+, and/or CD8+ gammadelta+ IEL may influence
      responses to cryptosporidiosis in athymic murine models, and that the increased
      percentage of alphabeta+ IEL in susceptible BALB/cJ nude mice could reflect a
      preferential expression during chronic C. parvum infection and/or might
      downregulate local protective responses.

PMID- 10882902
TI  - Trichodinid ectoparasites (Ciliophora: Peritrichida) of some River Nile fish,
      Egypt.
AB  - Four species of trichodinid ectoparasites (Ciliophora: Peritrichida) were
      collected from the gills of the following River Nile fish in Egypt: Hydrocynus
      forskalii, Mormyrus kannume, Schilbe mystus. These species are: Trichodina
      heterodentata Duncan, 1977, Trichodina fahaka sp. n., Trichodinella epizootica
      Raabe, 1950, Tripartiella dactylodentata sp. n. Photomicrographs and morphometric
      data are presented for each species.

PMID- 10882903
TI  - Characterisation of Bangladeshi Leishmania isolated from kala-azar patients by
      isoenzyme electrophoresis.
AB  - To identify the prevalent Leishmania species in Bangladesh, a total of nine
      patients aged 4-35 years, were studied; six (66.7%) of them were below 20 years
      of age. All the patients were clinically diagnosed to have visceral
      leishmaniasis; their haematological profile was in accordance with leishmaniasis
      and all were improved after treatment with sodium stibogluconate. All the
      aspirated materials (eight bone marrows and one splenic aspirate) yielded growth
      of Leishmania parasite in NNN media; Leishman-Donovan bodies were found in seven
      (77.8%) of them in a Giemsa stained smear. Aldehyde test (AT) was positive in all
      the nine cases examined, whereas, complement fixation test (CFT) was positive in
      seven (77.8%) and indirect fluorescent antibody test (IFAT) in eight (88.9%)
      cases. In this study, five of the nine isolates from kala-azar patients were
      characterised by isoenzyme analysis comparing with five WHO reference strains
      viz., Leishmania (Leishmania) donovani (DD8), L.(L.) donovani (HU3), L.(L.)
      infantum (IPT-1), L.(L.) tropica (K-27) and L.(L.) major (5-ASKH) using cellulose
      acetate electrophoresis. By analysing 11 soluble isoenzymes it was found that all
      five WHO reference strains had distinct electrophoretic mobility of the
      isoenzymes studied. No interspecies difference was observed amongst the five
      isolates from kala-azar patients examined and their isoenzyme profiles were
      consistent with WHO reference strain of L.(L.) donovani (DD8) but different from
      L.(L.) donovani (HU3).

PMID- 10882904
TI  - Cellular immunological responses of pheasant during endogenous development of
      Eimeria colchici.
AB  - We examined the time course and histological localisation of the developmental
      stages of Eimeria colchici. The prepatent period in the caeca of pheasants was 6
      days. The patent period began on day 7 post-infection (p.i.) and ended on day 11
      p.i. with peak production of oocysts on days 8-9. The peripheral blood
      lymphocytes of pheasant chicks showed a significant increase in proliferation to
      E. colchici antigen from day 5 p.i., with peak on day 14 p.i. The metabolic
      activity (respiratory burst) of heterophils increased on days 3, 4 and 14 p.i.
      The total number of peripheral blood leukocytes and lymphocytes in the infected
      pheasant chicks had increased by day 2 p.i. and reached a maximum on day 4 of the
      experiment. Days 5 and 6 p.i. were characterised by a drop in the number of these
      cells.

PMID- 10882905
TI  - Urinary schistosomiasis in southern Ghana: 1. Prevalence and morbidity assessment
      in three (defined) rural areas drained by the Densu river.
AB  - Epidemiological studies on urinary schistosomiasis were carried out in eight
      villages in the Ga and Akuapem South districts in Ghana. Single urine samples
      were collected from individuals aged 5 years and above between 10.00 and 14.00 h.
      The samples were examined for the presence of Schistosoma haematobium eggs using
      a filtration technique. Indirect morbidity was determined as the presence of
      microhaematuria and proteinuria using reagent strips, and macrohaematuria was
      recorded with the naked eye. Out of the study population of 3912 subjects, 2562
      (65.5%) submitted urine samples. The prevalence of a Schistosoma haematobium
      infection ranged between 54.8 and 60.0%. Infection rates increased by age with a
      peak in the 10-19 years category, and decreased with increasing age. Disease
      prevalence was higher in males aged 15 years and above in Areas 2 (Ntoaso and
      Sansami Amanfro) and 3 (Dom Faase, Papase, Chento and Gidi Kope), whereas it was
      higher among males aged 10 years and above in Area 1 (Ayikai Doblo and
      Akramaman). The intensity of infection was highest among children aged 10-14
      years in most of the villages. More than half of egg-positive children in this
      age group had a heavy infection (100 eggs and above in 10 ml of urine). Although
      both egg-positive and egg-negative individuals manifested variable degrees of
      macro- or micro-haematuria, microhaematuria was more prevalent among egg
      positives (chi(2)=918.5, d.f.=1, P<0.01). The degree of microhaematuria and
      proteinuria were significantly associated with the intensity of the infection.
      These results indicate a high transmission of disease in the study area.

PMID- 10882906
TI  - Protection of Merino lambs against Haemonchus contortus by trickle infection of
      neonates.
AB  - In two trials, lambs were trickle infected with 400 or 1000 infective larvae of
      Haemonchus contortus (HcL(3)), twice weekly for 4 weeks from the day of birth.
      Following anthelminthic treatment at 6 weeks (Trial 1) or 7 weeks of age (Trial
      2), lambs were challenged 1 week later with a trickle infection totalling 5000
      (Trial 1) or 10000 HcL(3) (Trial 2). In both cases, significant protection
      (P<0.05) ranging from 42 to 79% was achieved against egg and worm counts. Serum
      antibody responses as well as abomasal lymph node cell proliferation and
      production of interferon-gamma or interleukin (IL)-5 did not differ significantly
      between immunised and control lambs. The results are consistent with earlier
      findings that neonatal lambs can generate protective immunity against
      Trichostrongylus colubriformis, but the underlying mechanism(s) remain to be
      determined.

PMID- 10882907
TI  - Prevalence of antibodies to Toxoplasma gondii in the sera of rare wildlife in the
      Shanghai Zoological Garden, People's Republic of China.
AB  - The prevalence of antibodies to Toxoplasma gondii in the sera of rare wildlife in
      the Shanghai Zoological Garden, PR China, was examined using a modified
      agglutination test (MAT) and an enzyme-linked immunosorbent assay (ELISA). Forty
      one (35%) of 117 animals belonging to two classes, 10 orders, 18 families, 37
      genera and 52 species (including sub-species) were sero-positive for MAT. By MAT,
      T. gondii antibodies were found in 11.1% (4/36) of birds, in 25% (4/16) of
      primates, in 69.4% (25/36) of carnivores and in 27.6% (8/29) of herbivores.
      Thirty-three (33.7%) of 98 animals tested by protein A ELISA were sero-positive.
      By ELISA, T. gondii antibodies were found in none of 36 birds, in 33.3% (4/12) of
      primates, in 87.1% (27/31) of carnivores and in 10.5% (2/19) of herbivores.

PMID- 10882940
TI  - The different faces of pili bifurcati. A review.
AB  - Pili bifurcati is an uncommon hair shaft dysplasia characterized by bifurcation
      of the hair shaft. The two characteristics that define the dysplasia are: 1. Each
      bifurcation produces two separate parallel branches which fuse again to form a
      single shaft. 2. Each branch of the successive bifurcations is covered with its
      own cuticle. Currently, there is confusion between the terms "pili bifurcati" and
      "pili gemini". The name "pili gemini" is used to define a kinetic papilla that
      splits at the upper end from single to double-tipped during the anagen phase and
      consequently the same follicular matrix produces two different-sized hair shafts
      having separate cuticles that emerge through a single pilary canal. Pili gemini
      maintains the double tipped papilla and consequently the hair shaft does not fuse
      again. Papillar tips that divide into several tips will produce several hair
      shafts, that characteristically do not fuse again. When the same papilla changes
      its shape repeatedly during the anagen phase, it can produce hair shafts with
      bifurcations at irregular intervals: pili multibifurcati. And, as it is also
      possible for one of the new papillae to split again in two, the hair shaft may be
      doubly bifurcated: pili bi, bifurcati. Pili bifurcati should be distinguished
      from acquired splitting of hair shafts that do not represent true bifurcations
      because the two split parts are never surrounded by a complete cuticle. Such
      acquired splitting may be called "central trichoptilosis".

PMID- 10882941
TI  - Growth factors in early hair follicle morphogenesis.
AB  - Classic studies show the embryonic epidermis and mesenchyme must communicate
      during embryogenesis to form a hair follicle. However, the methods of
      communication between and within the epidermis and dermis that regulate hair
      follicle development are poorly understood. Potentially, the epidermis and dermis
      communicate by utilizing cell surface receptor expression, cell adhesion
      molecules, extra cellular matrix products, and chemical messaging via secreted
      molecules. With each product involved in cell communication, intensity, potency,
      time of production during hair follicle development, production duration, and
      spatial distribution must all be considered. The total sum of these factors must
      provide adequate information to cells about their respective location and role
      within the developing hair follicle. Here we review the potential contribution
      made to hair follicle embryogenesis by growth factors and their receptors.

PMID- 10882943
TI  - Hairless guinea pig skin: anatomical basis for studies of cutaneous biology.
AB  - In order to characterize the microscopic anatomy of hairless guinea pig (HL-GP)
      skin, we utilized light microscopy with a computer-assisted image analysis
      system, scanning electron microscopy (SEM) and transmission electron microscopy
      (TEM). SEM revealed that the hair shafts of HL-GPs were thin, short, extremely
      irregular in diameter and often twisted and curled. The HL-GP epidermis was of
      similar thickness to that of human skin with distinct strata, serrated/non
      serrated basal keratinocytes and shallow dermal papillae. The density of
      Langerhans cells in epidermal sheets, visualized by adenosine-s-triphosphatase
      staining, was similar to that of normal-haired guinea pigs (HD-GPs), although the
      dendrites of HL-GPs were thicker and shorter than those of HD-GPs. The dermal
      vasculature of HL-GPs was well-developed and similar to that of humans,
      demonstrating a network of vertically oriented capillary loops. HL-GPs had
      significantly more dendritic or spindle-shaped dermal interstitial cells than
      humans and HD-GPs. Collectively, these data suggest that HL-GP skin is more
      similar to human skin than to the skin of HD-GPs and other rodents and,
      therefore, the HL-GP may be a useful animal for studying cutaneous biology,
      experimental pathology, pharmacology and toxicology.

PMID- 10882942
TI  - In vivo fluorescence kinetics and photodynamic therapy efficacy of delta
      aminolevulinic acid-induced porphyrins in basal cell carcinomas and actinic
      keratoses; implications for optimization of photodynamic therapy.
AB  - Photodynamic therapy (PDT) with topical d-aminolevulinic acid (ALA) has become a
      therapeutic option of growing interest for superficial non-melanoma precancerous
      and malignant lesions. After application of ALA, in situ conversion to endogenous
      porphyrins is accomplished in a gradual manner. Therefore, the determination of
      fluorescence kinetics and spatial distribution in vivo versus time is a crucial
      point for the success of ALA-PDT. Seventeen basal cell carcinomas (BCC) and 20
      actinic keratoses (AK) were enrolled in this study. In 5 BCC and 4 AK, in vivo
      fluorescence kinetics were performed over 24 hrs and for the remaining lesions
      between 2 and 7 hrs after ALA application. In vivo spatial and quantitative
      detection of the fluorescence intensity versus time showed considerable
      variations among tumors of the same type, so light irradiation was performed
      according to patient individualities. Both BCC and AK showed maximal median
      fluorescence intensity at 4-6.5 hrs post-application. In the present study, a
      high cure rate was proven after topical ALA-PDT (70.6% in BCC and 85% in AK). The
      results of fluorescence studies suggest that optimum irradiation time for BCC is
      approximately 3.5-5 hrs and for AK 5 hrs after ALA application, when relative
      maximal fluorescence intensity in correlation with fluorescence selectivity on
      the lesion, is obtained.

PMID- 10882944
TI  - Up-regulated perforin expression of CD8+ blood lymphocytes in generalized non
      anaphylactic drug eruptions and exacerbated psoriasis.
AB  - Perforin expressed in CD8+ cytotoxic T cells is known to mediate the lysis of
      target cells carrying microbial as well as tumor-associated antigens, and to be
      involved in autoimmune and transplant reactions. The aim of the present
      investigation was to study the role of perforin- and CD8-expressing effector
      lymphocytes from peripheral blood in patients with generalized inflammatory skin
      diseases. Mononuclear cells were separated from peripheral venous blood and
      permeabilized by 0.1% saponin. The co-expression of cytoplasmatic perforin and
      cell membrane-residing CD8 was determined in lymphocytes by immuno-flow
      cytometry. Patients affected by generalized macular-papular drug eruptions (n =
      14), drug-unrelated acute urticaria (n = 10) and drug-independently exacerbated
      psoriasis (n = 11, PASI scores ranging from 25 to 35), as well as control
      individuals not affected by any inflammatory skin disease (n = 10) were enrolled.
      Additionally, n = 5 patients with drug-induced Stevens-Johnson syndrome (SJS)
      were included. The average proportion of CD8+ peripheral lymphocytes co
      expressing perforin in generalized drug eruptions (68.8+/-24.9%) and exacerbated
      psoriasis (67.2+/-17.1%) differed significantly from the controls (43.5+/-11.6%;
      p 0. 05), whereas no significant difference for acute urticaria (58.2+/-23.1%)
      could be measured. In each of the 5 SJS patients treated by high dose systemic
      steroids the parameter substantially declined during the first 7 days after
      admission from an average value of 81. 6% down to 33.0%. Thus, as compared to
      controls we observed an increased perforin+ proportion of CD8+ lymphocytes in
      generalized drug eruptions and in exacerbated psoriasis but not in acute
      urticaria. Therefore the parameter showed some specificity as a marker of
      distinct inflammatory skin disorders, and proved to be useful in monitoring the
      disease activity of SJS under anti-inflammatory medication. Furthermore, the
      findings point to a possible crucial role of CD8+ lymphocytes in the pathogenesis
      of psoriasis.

PMID- 10882945
TI  - A low-salt medical water reduces irritancy of retinoic acid in facial acne.
AB  - Although effective medications are available for the treatment of acne, tolerance
      problems may preclude adequate treatment regimens such as topical retinoic acid,
      and reduce patient compliance. The present study was conducted to evaluate
      whether a medical water (Avene) in conjunction with retinoic acid may improve
      local tolerance in acne. A controlled, open, randomised, multicentric study was
      completed after 28 days of treatment in 69 acne patients, 34 applying a retinoic
      acid preparation alone, and 35 applying retinoic acid in association with the
      water spray used ad libitum. Topical retinoic acid treatment induced prominent
      signs of irritation in both groups. However, a statistically significant
      reduction between the two treatment groups could be demonstrated on scaling at
      all assessment visits (p< or =0.02, Wilcoxon test). No significant water effect
      on erythema, burning and itching was shown during the treatment period. The
      overall tolerance assessed by the investigator was significantly improved with
      the water (p = 0.04, Wilcoxon). Taken together, water with a low mineral content
      appears to be a promising adjunctive treatment for improving the tolerance of
      topical retinoids in acne.

PMID- 10882946
TI  - Histopathological changes in the hair follicle after irradiation of long-pulse
      alexandrite laser equipped with a cooling device.
AB  - Several laser systems are currently used for epilation. However, the optimal
      parameters and treatment protocols remain largely unknown. In this study, the
      histopathological changes in the hair follicles after long pulsed alexandrite
      laser irradiation are discussed and the clinical application of irradiation
      energy at the time of treatment is described. The laser used in this study is
      equipped with a computer controlled cooling device. A histopathological study was
      performed to compare the differences in the degree of degeneration in the
      epidermis and follicles treated with and without the cooling device. In
      comparison with normal hair papilla, in the laser irradiated skin, injury of
      melanin containing cells and hair shafts and external root-sheaths in the
      periphery were observed, while the epidermis was completely protected by the
      cooling device. The condition of the hair papilla of the tissue irradiated at a
      fluence of 25 J/cm2 with a spot diameter of 15 mm and 20 J/cm2, with a spot
      diameter of 18 mm were investigated thoroughly. Swollen papilla and selective
      destruction of the site where melanocytes were present were observed. The results
      of this study strongly indicate the efficacy of a long-pulsed alexandrite laser
      equipped with a computer controlled cooling device for clinical depilation.

PMID- 10882947
TI  - The prevalence and management of onychomycosis in diabetic patients.
AB  - The incidence of diabetes mellitus is increasing throughout the world. Diabetic
      patients must cope with the serious complications of this condition, such as
      renal disease, retinopathy and the diabetic foot. To date, very few studies have
      examined the prevalence of onychomycosis among diabetic subjects. However, two
      recent studies highlight an increased incidence of onychomycosis and other
      superficial fungal infections in these patients. Nail and other fungal skin
      infections pose a greater risk in this patient population because of the possible
      sequelae. In addition, impaired sensation in the lower extremities can mask minor
      abrasions and ulcerations on a diabetic patient's foot, which may develop into
      serious bacterial infections and contribute to the severity of the diabetic foot.
      Given the potential morbidity that may result from fungal infections of the
      extremities, effective treatment is of paramount importance. An ideal antifungal
      agent should combine a broad spectrum of activity with good efficacy and a
      favorable safety profile.

PMID- 10882948
TI  - Sebaceous carcinoma arising on actinic keratosis.
AB  - We report two cases of sebaceous carcinoma arising on actinic keratosis. The
      first patient, a 75-year-old female, had a granuloma pyogenicum-like tumor on her
      left temple, and the second patient, an 81-year-old female, developed a tumor
      with erythema on her left cheek. In both cases, histopathological examination
      revealed findings typical of sebaceous carcinoma in the center of the tumors, and
      in the periphery, actinic elastosis and intraepidermal proliferation of squamoid
      atypical cells without vacuolation was observed. Immunohistochemical examinations
      using six antibodies also revealed that neoplastic cells of both cases
      demonstrated sebaceous differentiation. These cases suggest that extraocular
      sebaceous carcinoma may arise from actinic keratosis.

PMID- 10882949
TI  - Tick bite by Haemaphysalis megaspinosa - first case.
AB  - We describe the first case of tick bite by Haemaphysalis megaspinosa. The tick
      was found on the skin at the right occipital area in a 5-year-old girl, who had
      gone on a picnic twice to a mountain 1 and 5 days before she noticed the tick.
      The tick was surgically removed. The tick was identified as an adult female of
      Haemaphysalis megaspinosa from its morphological characteristics. This is the
      first report of tick bite by Haemaphysalis megaspinosa.

PMID- 10882950
TI  - Transverse leukonychia following chemotherapy in a patient with Hodgkin's
      disease.
AB  - Nail changes often represent diagnostic hallmarks for a variety of systemic
      diseases. The awareness of drug-induced nail injuries is important in order to
      avoid unnecessary diagnostic activities. We observed a 21-year-old female patient
      with Hodgkin's lymphoma, who developed transverse leukonychia of all fingernails
      associated with polychemotherapy.

PMID- 10882951
TI  - Oral focal epithelial hyperplasia.
AB  - Focal epithelial hyperplasia (FEH) or Heck disease, is a rare viral infection of
      the oral mucosa caused by HPV 13 or HPV 32. In Caucasians there have been only a
      few cases reported. We present the first case in Greece in a young Caucasian girl
      in which HPV 13 was detected with PCR analysis. The patient was successfully
      treated with CO2 laser.

PMID- 10882952
TI  - Ichthyosis revealing coeliac disease.
AB  - We describe the case of a twenty-nine year-old woman presenting a lamellar
      desquamation on the abdomen, submammary folds and on the limbs. During recent
      years the patient suffered neither from bowel disorders, nor from dryness of the
      skin. Laboratory tests revealed high values of parathormone and a high level of
      antiendomysial antibodies. The total bone-mineral density was about 78% of normal
      levels. A duodenal mucous membrane specimen showed total atrophy of the villi.
      Skin biopsy revealed an acquired ichthyosis mimicking an ichthyosis vulgaris. The
      patient underwent a gluten-free diet, supported by folic acid and vitamin D and
      six months later, after the regression of secondary hyperparathyroidism, a
      remarkable improvement of the cutaneous symptoms was obtained.

PMID- 10882953
TI  - Current understanding of androgenetic alopecia. Part II: clinical aspects and
      treatment.
AB  - The first signs of androgenetic alopecia (AGA) may start to develop with the
      onset of puberty. The prevalence of progressive AGA approaches 50% of Caucasian
      men and women beyond the age of 40; whereas in Asian, native American and African
      American men the prevalence is lower and AGA is less severe. Only exceptionally
      laboratory tests or scalp biopsies are needed to confirm the diagnosis. Therefore
      the clinical assessment of AGA is largely a matter of common sense and practice.
      The loss of hair is often trivialised, but hair loss may have profound effects on
      a patient's well-being and quality of life. The treatment of AGA is obscured by
      myths. Many products or procedures are advertized for the treatment of AGA such
      as vitamins, trace elements, exotic herbs, amino acids, "soft laser", scalp
      massage, etc. Most of these techniques or substances have never been verified in
      sound clinical trials. Because of the psychosocial impact of hair loss, however,
      it is important to explain to patients what they may expect in terms of
      continuing hair loss, and that response to any therapy may be slow and may
      include hair regrowth or only retardation of further thinning. The aim of AGA
      treatment is to reverse or to stabilize the process of HF miniaturization and
      with this overview we summarize the present treatment modalities for both men and
      women.

PMID- 10882954
TI  - Magnetic imaging of colonoscopy: an audit of looping, accuracy and ancillary
      maneuvers.
AB  - BACKGROUND: Colonoscopy is one of the most frequently performed outpatient
      examinations. However, the procedure is still technically challenging, largely
      due to unpredictable looping during insertion. The aims of this study were (1) to
      assess the frequency of loop formation and types of loop during colonoscopy, (2)
      to determine the accuracy of the endoscopist's assessment of the anatomic
      location of the endoscope tip and of the presence and type of endoscope loop
      formation, and (3) to determine the efficacy of abdominal compression and change
      in patient position in promoting colonoscope advancement. METHODS: Consecutive
      patients undergoing routine, day-case colonoscopy were studied using real-time,
      three-dimensional magnetic endoscope imaging. All examinations were performed by
      expert colonoscopists, blinded to the imager view. The endoscopist estimated the
      position of the colonoscope tip, assessed when and what type of loop had formed,
      and the efficacy of ancillary maneuvers such as hand pressure or patient position
      change. The magnetic imager view of each procedure was recorded and
      retrospectively analyzed. RESULTS: One hundred complete colonoscopies were
      performed. Looping occurred in 91% with N-sigmoid (79%) and deep transverse (34%)
      being most common. Most loops (69%) were incorrectly diagnosed by the
      endoscopist. Atypical loops were more common in women than men (p = 0.025). The
      endoscopist's assessment of tip location was correct 85% of the time overall, but
      100% in the cecum. Abdominal pressure was less effective (54 of 145 times, 37%)
      than patient position change (95 of 144 times, 66%) in promoting endoscope tip
      advancement. CONCLUSIONS: Looping occurs frequently during routine colonoscopy.
      Although the endoscopist's assessment of tip location is fairly accurate, the
      majority of colonoscope loops are incorrectly appreciated. Although used
      frequently, ancillary maneuvers (abdominal compression and patient position
      change) are effective in only 52% of attempts.

PMID- 10882955
TI  - Long-term results after endoscopic pancreatic stent placement without pancreatic
      papillotomy in acute recurrent pancreatitis due to pancreas divisum.
AB  - BACKGROUND: There is no consensus regarding the appropriate endoscopic treatment
      for acute recurrent pancreatitis associated with pancreas divisum. Endoscopic
      papillotomy of the minor papilla appears to yield improvement in most cases, but
      optimal depth and height have not been defined. METHODS: Endoscopic pancreatic
      stent placement after minor papilla dilation was performed in 25 patients with
      pancreas divisum and acute recurrent pancreatitis. Five patients drank alcohol
      daily; no other cause of pancreatitis was detected. After adequate dilation, a
      transpapillary pancreatic stent (5F to 7F, 5 to 7 cm) was inserted over a
      guidewire into the dorsal duct. The stent was replaced twice, after 2- to 3-month
      intervals. RESULTS: While stents were in place, no further episodes of
      pancreatitis occurred in 23 patients. However, dorsal duct changes of unknown
      clinical significance were seen in 21 cases. At mean follow-up of 24 months
      (range 3 to 70 months) after stent removal, 19 (76%) remained symptom free.
      Pancreatitis recurred in 6 patients during the follow-up after final stent
      removal; no further pancreatitis occurred in 2 of 3 who underwent repeat stent
      insertion. Complications in the series were minimal. CONCLUSION: Endoscopic
      pancreatic stent placement after minor papilla and dorsal duct dilation, without
      endoscopic papillotomy, provided safe and effective endoscopic treatment in
      patients with pancreas divisum and acute recurrent pancreatitis.

PMID- 10882956
TI  - What are the long-term results of endoscopic pancreatic sphincterotomy?
AB  - BACKGROUND: Endoscopic pancreatic sphincterotomy has been touted as effective
      therapy for chronic pancreatitis and unexplained abdominal pain resulting from
      pancreatic sphincter dysfunction. Although short-term data are encouraging, there
      are no reports on how these patients fare beyond the first few months. METHODS:
      We performed a retrospective review of records on all patients who had pancreatic
      sphincterotomy during a 4-year period between August 1992 and November 1996.
      Chronic pancreatitis was diagnosed by pancreatography. Patients were evaluated
      for symptomatic response to pancreatic sphincterotomy and clinical improvement
      was defined as greater than 50% reduction in the magnitude of pain. RESULTS:
      Fifty-five patients had pancreatic sphincterotomy including patients with (n =
      40) and without (n = 15) chronic pancreatitis. After a median follow-up of 16
      months, 60% of all patients reported improvement of pain scores (3.6 +/- 3.4 vs.
      8.8 +/- 1.8; p < 0.01) with the best response in patients without evidence of
      chronic pancreatitis. Complications of pancreatic sphincterotomy included
      pancreatitis in 5 patients (9%), bleeding in 2 (3.6%) and early stent occlusion
      in 5 patients (9%). There were no deaths. CONCLUSIONS: In a subgroup of patients
      with pancreatic sphincter dysfunction, endoscopic pancreatic sphincterotomy
      results in significant sustained clinical improvement.

PMID- 10882957
TI  - Noninvasive tests as a substitute for histology in the diagnosis of Helicobacter
      pylori infection.
AB  - BACKGROUND: Rapid urease tests for Helicobacter pylori have a sensitivity of 80%
      to 90%. Therefore histologic examination of gastric biopsies is recommended as a
      "backup" diagnostic test in rapid urease test-negative patients. However,
      noninvasive tests (urea breath test, serology, whole blood antibody tests) may
      provide a more rapid diagnosis and be less expensive but offer similar accuracy.
      METHODS: Sixty-seven patients (no prior treatment for H pylori, no proton pump
      inhibitors, antibiotics, or bismuth within 4 weeks) undergoing endoscopy for
      evaluation of dyspepsia symptoms and testing rapid urease test-negative by antral
      biopsy were enrolled. All had the following tests: gastric biopsies (2 antral, 1
      fundus; H&E and Alcian Yellow stain) examined for gastritis and H pylori; (13)C
      UBT; capillary blood for whole blood rapid antibody tests: FlexSure HP, QuickVue,
      AccuStat, and Stat-Simple Pylori; serum for FlexSure HP; HM-CAP enzyme-linked
      immunoassay. H pylori infection was diagnosed (reference standard) if chronic
      gastritis was present on histology and at least 2 of the 3 following tests were
      positive: urea breath test, H pylori organisms unequivocally demonstrated in
      biopsies on special stain, and/or enzyme-linked immunoassay. The test and
      treatment costs per patient were calculated. RESULTS: Of 67 patients with a
      negative rapid urease test, 4 were positive for H pylori. None had active peptic
      ulcer disease. Histology only identified 1 patient with organisms visible on
      special stain. Using chronic active gastritis (neutrophilic and mononuclear
      infiltrate) as a diagnostic criterion for H pylori, 6 patients would have been
      judged positive. However, only 2 of these were truly positive by the reference
      standard (positive predictive value 33%). Negative predictive value for presence
      of organisms and chronic active gastritis was 95% and 97%, respectively. All of
      the noninvasive tests identified all 4 truly positive patients correctly. Urea
      breath test and FlexSure whole blood assay yielded a substantial number of false
      positive results (positive predictive value 31% and 36%, respectively); positive
      predictive value for the other tests ranged from 50% to 80%. All tests except
      histology had a negative predictive value of 100%. Histology was the most costly
      test (p < 0. 001 compared with all other tests), followed by urea breath test and
      HM-CAP serology (p < 0.001 compared with all rapid antibody tests). CONCLUSIONS:
      Whole blood or serum antibody testing is a rapid, accurate, and cost-effective
      means for establishing H pylori status in rapid urease test-negative patients.
      Whole blood or serology rapid antibody testing should substitute for histology
      when the patient has not been previously treated for H pylori.

PMID- 10882958
TI  - Effect of Helicobacter pylori eradication on malignant transformation of gastric
      adenoma.
AB  - BACKGROUND: A nonrandomized trial of Helicobacter pylori eradication was
      conducted in patients with endoscopically diagnosed gastric adenoma to determine
      the long-term effect of antimicrobial treatment on progression of the adenoma.
      METHODS: Of 64 patients with an endoscopically diagnosed gastric adenoma and H
      pylori infection, 32 were treated with omeprazole and antibiotics to eradicate
      the infection, and 32 were not. RESULTS: During 2 years of follow-up, 4 (12.5%)
      of the 32 patients in the untreated group developed an early stage, intestinal
      type gastric cancer, whereas no gastric cancer was found in the 32 patients in
      the treated group. CONCLUSION: H Pylori eradication may inhibit progression of
      gastric adenoma to carcinoma.

PMID- 10882959
TI  - Patterns of endoscopic follow-up after surgery for nonmetastatic colorectal
      cancer.
AB  - BACKGROUND: Endoscopic examinations of the colon are often recommended for
      surveillance following colorectal cancer resection. The actual use and outcome of
      this testing are not known. METHODS: Five thousand seven hundred sixteen patients
      65 years of age or older with local or regional stage colorectal cancer diagnosed
      in 1991 were identified through the Surveillance Epidemiology and End Results
      registry. All inpatient and outpatient Medicare claims from 6 months after
      diagnosis through the end of 1994 were examined to determine use of endoscopic
      procedures. RESULTS: One or more colonoscopies were performed in 51%, with an
      average of 2.9 procedures performed among those tested; sigmoidoscopy was
      performed in 17%. The rate of colonoscopy was highest during the initial 18
      months. Polypectomy was performed in 21% of all patients, and subsequent primary
      colorectal tumors were diagnosed in 1.3%. Factors associated with colonoscopy and
      sigmoidoscopy use included younger age, survival through follow-up, and
      geographic region; sigmoidoscopy was also more common in relation to rectal
      cancers. CONCLUSIONS: There is variability in the use of endoscopic procedures
      following potentially curative resection for colorectal cancer, with patient
      related factors and local practice patterns accounting for the variation. Further
      studies are needed to elicit the reasons for lack of follow-up and adherence to
      practice guidelines.

PMID- 10882960
TI  - The ASGE guidelines for the appropriate use of colonoscopy in an open access
      system.
AB  - BACKGROUND: Appropriateness of indications is essential to the rational
      utilization of resources. The aim of this study was to evaluate the appropriate
      use of colonoscopy in an open access system and to assess whether the American
      Society for Gastrointestinal Endoscopy (ASGE) guidelines are useful in clinical
      practice. METHODS: The indication for colonoscopy was assessed on 3000
      consecutive examinations performed at 7 institutions. RESULTS: The rate of
      colonoscopies "generally not indicated" according to the ASGE guidelines was
      24.5% for outpatients and 15.5% for inpatients; the rates of examinations
      performed for an indication not listed in the ASGE guidelines were 12% and 20.1%,
      respectively. Generally not indicated colonoscopies were significantly less
      frequent for procedures requested by gastroenterologists or family physicians
      than those requested by other specialists, but were similar. Most generally not
      indicated examinations requested by gastroenterologists were for routine follow
      up of patients with inflammatory bowel disease; when these patients were
      excluded, the rate of generally not indicated endoscopies requested by
      gastroenterologists was also lower than the corresponding rate for examinations
      requested by family physicians. CONCLUSIONS: In Italy, the rate of colonoscopies
      performed for generally not indicated reasons is high, particularly among
      examinations not requested by a gastroenterologist. Many colonoscopies are
      performed for indications not listed in the ASGE guidelines.

PMID- 10882961
TI  - The utilization of flexible sigmoidoscopy by family practitioners after residency
      training.
AB  - BACKGROUND: Flexible sigmoidoscopy is routinely performed by family practice
      physicians, most of whom receive training in postgraduate education programs. The
      aim of this study was to assess the utilization of flexible sigmoidoscopy by
      family practitioners who received training during residency. METHODS: Family
      practitioners who underwent training in flexible sigmoidoscopy during their
      residency were contacted by phone or mail and polled regarding their current use
      of flexible sigmoidoscopy and assessment of their previous training. RESULTS:
      Forty-two graduates were contacted; 76% were certified (according to our
      predefined criteria) during training and 74% were currently performing flexible
      sigmoidoscopy. Of those who were certified, 87% were currently using flexible
      sigmoidoscopy compared with 45% of those who did not receive certification (p =
      0.02). Training during the last year of residency was more likely to be
      associated with current use of flexible sigmoidoscopy than earlier training (69%
      vs. 30%, p = 0.03). Certification was associated with more procedures during
      training (24.3 +/- 1.7 vs. 16.6 +/- 3.1, p < 0.05). Current users performed a
      mean of 4.3 +/- 0.75 procedures/month; most reached 40 cm in depth of insertion
      and completed the procedure in 17.2 +/- 1.2 minutes. Of patients undergoing
      flexible sigmoidoscopy, 13% were ultimately referred for colonoscopy. Most
      practitioners considered their training useful and only 9.6% had obtained
      additional training outside residency. CONCLUSIONS: Most family practitioners
      certified in flexible sigmoidoscopy during residency performed the procedure in
      their practices. Depth of insertion and time for completion of the procedure seem
      to be adequate.

PMID- 10882962
TI  - Conscious sedation and cardiorespiratory safety during colonoscopy.
AB  - BACKGROUND: Cardiorespiratory events during colonoscopy are common. The effect of
      sedative premedication on cardiorespiratory parameters during colonoscopy has not
      been studied in controlled, prospective trials. METHODS: One hundred eighty
      patients undergoing colonoscopy were divided into 3 groups: (1) sedation with
      intravenous midazolam (midazolam group); (2) sedation with intravenous saline
      (placebo group); and (3) no intravenous cannula (control group). Arterial oxygen
      saturation (SaO(2)), systolic and diastolic blood pressure and continuous
      electrocardiogram were recorded prior to, during and after the endoscopic
      procedure. RESULTS: Midazolam produced lower SaO(2) values during colonoscopy
      compared with placebo or control groups (p < 0.001, repeated measures analysis of
      variance). Systolic and diastolic blood pressure during colonoscopy were lower in
      the midazolam group than in the placebo group (p < 0.01 and p < 0.05,
      respectively), but no difference was found between the midazolam and the control
      groups. Hypotension (systolic blood pressure less than 100 mm Hg) occurred more
      frequently in the midazolam group (19%) than in the placebo (3%; p < 0.01) or
      control groups (7%; p < 0.05). ST-segment depression developed in 7% of patients
      during the recording with no difference between the groups. In 75% of cases ST
      depression appeared prior to the endoscopic procedure. CONCLUSIONS: Premedication
      with midazolam induced a statistically significant decrease in arterial oxygen
      saturation and increased the risk for hypotension. However, colonoscopy proved to
      be a safe procedure both with and without sedation.

PMID- 10882963
TI  - Endoscopic management of postoperative biliary complications in orthotopic liver
      transplantation.
AB  - BACKGROUND: Surgery, percutaneous cholangiography, and endoscopic retrograde
      cholangiopancreatography (ERCP) have been used in the management of biliary
      complications after orthotopic liver transplantation with varied results. We
      assessed the role of ERCP in the diagnosis, treatment, and outcome of post
      orthotopic liver transplantation biliary complications. METHODS: We
      retrospectively reviewed the records of 260 patients who underwent orthotopic
      liver transplantation. We examined the number of patients referred for ERCP and
      the indication, diagnosis, therapeutic intervention, success, and complication
      rate of ERCP post orthotopic liver transplantation. We compared the survival and
      retransplantation rates of the patients who underwent ERCP with a control group
      of post-orthotopic liver transplantation patients not undergoing ERCP. RESULTS:
      Of the 260 patients undergoing orthotopic liver transplantation, 64 (24.6%)
      underwent 137 ERCPs. Two categories of indications for ERCP were identified: bile
      leak (n = 31) and obstruction (n = 39). ERCP identified the site of the bile leak
      in 27 of 31 cases (87.1%) and the leak was treated by endoscopic means in 26 of
      31 (83.9%). Treatment success differed significantly based on location of the
      leak (T tube, 95.2% vs. anastomosis, 42.9%; p = 0. 009). ERCP identified the site
      of obstruction in 37 of 39 cases (94. 9%) and obstruction was relieved by
      endoscopic means in 25 of 35 cases (71.4%). ERCP was significantly less
      successful in the treatment of biliary casts (25.0%, p = 0.048). There was no
      difference in survival or retransplantation between patients who did and did not
      undergo ERCP. CONCLUSION: ERCP should be the primary method for diagnosis and
      treatment of post-orthotopic liver transplantation biliary complications.
      Endoscopic therapy is safe and effective for the majority of post-orthotopic
      liver transplantation complications and temporizes management for those
      complications that may require surgery.

PMID- 10882964
TI  - Duodenal stenosis after endoscopic biliary metallic stent placement for malignant
      biliary stenosis.
AB  - BACKGROUND: Some patients who undergo endoscopic insertion of biliary metallic
      stents for malignant biliary stenosis later develop symptomatic duodenal stenosis
      due to tumor invasion. METHODS: We compared the development of symptomatic
      duodenal stenosis in patients who had undergone endoscopic biliary metallic stent
      insertion (metallic stent group) with that in patients who had undergone either
      endoscopic biliary drainage or percutaneous transhepatic biliary drainage with a
      plastic stent (nonmetallic stent group). Fourteen patients in the metallic stent
      group were matched with 14 patients in a nonmetallic stent group. All patients
      had a Karnofsky performance status score of greater than 90% and were clinical
      stage IV when they underwent biliary decompression. RESULTS: Although there was
      no difference in survival time between the 2 groups, 5 of 14 patients in the
      metallic stent group developed symptomatic duodenal stenosis due to tumor
      invasion during the observation period whereas this occurred in only 1 of 14
      patients in the nonmetallic stent group. Multiple logistic regression analysis
      indicates that the type of stent (p = 0.022) and survival time (p = 0.002) are 2
      independent prognostic factors for the development of symptomatic duodenal
      stenosis. CONCLUSIONS: Patients treated with endoscopic biliary metallic stent
      insertion are prone to develop symptomatic duodenal stenosis due to tumor
      invasion compared with those treated with either endoscopic retrograde biliary
      drainage or percutaneous transhepatic biliary drainage with a plastic stent.

PMID- 10882965
TI  - Peroral pancreatoscopy in the diagnosis of mucin-producing tumors of the
      pancreas.
AB  - BACKGROUND: Mucin-producing tumor of the pancreas is an increasingly recognized
      clinical entity. However, the differentiation of benign from malignant mucin
      producing tumors of the pancreas is challenging. Peroral pancreatoscopy as
      recently developed may have potential for the diagnosis of mucin-producing tumors
      of the pancreas. METHODS: The subjects were 41 patients with clinically diagnosed
      mucin-producing tumors of the pancreas, 40 of whom underwent surgical resection.
      Autopsy findings were available in another patient with unresectable disease.
      Histologically, hyperplasia was identified in 3 patients, mildly atypical adenoma
      in 11, severely atypical adenoma in 16, and adenocarcinoma in 11. Peroral
      pancreatoscopy was performed before surgery or pathologic examination. The
      findings were retrospectively evaluated and compared with the histopathologic
      diagnosis. RESULTS: Pancreatoscopic observation was successful in 30 patients
      (73.2%). Elevated lesions were identified in 22 (73.3%). Villous or vegetative
      elevations and red color markings were frequently found in severely atypical
      adenoma or adenocarcinoma. Tumor location (main or branch duct type) did not
      correlate with survival after resection. Partial resection was performed in 7 of
      30 patients with nonmalignant tumors and resulted in favorable outcomes.
      CONCLUSION: Peroral pancreatoscopy can be used to differentiate benign mucin
      producing tumors of the pancreas (hyperplasia and mildly atypical adenoma) from
      the more dysplastic lesions (severely atypical adenoma and adenocarcinoma) and
      may provide useful information for determining the type of surgery to be
      performed.

PMID- 10882966
TI  - The double duct sign in patients with malignant and benign pancreatic lesions.
AB  - BACKGROUND: The double duct sign, a simultaneous stenosis of the common bile duct
      and the pancreatic duct by endoscopic retrograde cholangiopancreatography (ERCP),
      has been reported to predict the presence of pancreatic cancer with a high degree
      of certainty. METHODS: To test the specificity of the double duct sign for
      pancreatic cancer in patients with malignant and benign pancreatic lesions, we
      have reviewed all ERCP films obtained during a 24-month period (n = 1209) and
      corresponding clinical follow-up data obtained during a period of 4 years.
      RESULTS: Forty-three patients were identified as having a double duct stenosis on
      ERCP, 15% of whom did not have pancreatic carcinoma. In 4 patients chronic
      pancreatitis was confirmed by serial histologic sections of the surgical
      specimen. Data on the lengths of the stenotic segment in either the pancreatic
      duct or the bile duct did not contribute to a better discrimination between
      benign and malignant disease. CONCLUSION: The specificity of the double duct sign
      in predicting the presence of pancreatic cancer appears to be lower than
      previously reported. Better discrimination between malignant and benign disease
      of the pancreas will be difficult to achieve with existing imaging techniques.

PMID- 10882967
TI  - Biliary cast syndrome: successful endoscopic treatment.

PMID- 10882968
TI  - Endoscopically visible coil after embolization for bleeding duodenal ulcer.

PMID- 10882970
TI  - Three-dimensional esophageal varix model quantification of variceal volume by
      high-resolution endoluminal US.
AB  - BACKGROUND: The purpose of this study was to evaluate the accuracy and
      reproducibility of three-dimensional volume measurements by high-resolution
      endoluminal ultrasound in an esophageal varix model. METHODS: An esophageal varix
      model was made by filling three esophageal dilatation catheters with various
      volumes of water. A 20 MHz ultrasonography transducer was then pulled along the
      length of the catheters at a constant rate (1.25 mm/sec) while videotaping the
      procedure. Cross-sectional surface area measurements of each catheter were taken
      every second and the cross-sectional surface area was multiplied by the length of
      each catheter, as determined by high-resolution endoluminal ultrasound, to
      determine the volume in each catheter. Interobserver variability was calculated,
      and three-dimensional reconstruction was performed. RESULTS: The measured volumes
      corresponded closely with the actual volumes with an error ranging from 0% to
      15.4%. The correlation between actual and measured volumes was r = 0.988. The
      interobserver variability ranged from r = 0.951 to r = 0.994. Actual esophageal
      varices were then imaged in a similar fashion to determine the feasibility of
      this method in patients with esophageal varices. CONCLUSIONS: High-resolution
      endoluminal ultrasound is an accurate and reproducible method of measuring
      volumes in an esophageal varix model and can be used in a clinical setting to
      determine variceal volume. Volume studies are now underway in human subjects.

PMID- 10882969
TI  - Augmentation of lower esophageal sphincter pressure and gastric yield pressure
      after radiofrequency energy delivery to the gastroesophageal junction: a porcine
      model.
AB  - BACKGROUND: An endoscopic technique that eliminates gastroesophageal reflux
      disease would be of benefit to patients. The endoscopic delivery of
      radiofrequency energy to the porcine gastroesophageal junction was investigated
      and its effect on lower esophageal sphincter pressure, gastric yield pressure,
      and histology was assessed. METHODS: Twenty pigs underwent esophageal manometry
      and endoscopic injection of botulinum toxin (100 units) into the lower esophageal
      sphincter. After 1 week, animals were randomized to radiofrequency energy
      treatment of the gastroesophageal junction with a 4- needle catheter and
      thermocouple-controlled generator (n = 13) or no further intervention (control, n
      = 7). At 9 weeks, animals underwent esophagoscopy, manometry, gastric yield
      pressure determination, and sacrifice for histopathologic evaluation. RESULTS:
      Mean lower esophageal sphincter pressure declined by 3.7 +/- 2.6 mm Hg (control,
      p = 0.03) vs. 0.97 +/- 5.8 mm Hg (radiofrequency, p = 0.29) after 9 weeks. Mean
      gastric yield pressure was 24.9 +/- 8.2 mm Hg (control), compared with 43.4 +/-
      10. 7 mm Hg (radiofrequency) (p = 0.0007). Histopathologic assessment
      demonstrated normal mucosa, mild fibrosis, and no inflammation. CONCLUSIONS:
      Radiofrequency energy delivery reversed much of the lower esophageal sphincter
      pressure reduction achieved with botulinum toxin injection and augmented gastric
      yield pressure by 75% compared with controls. Given the safety of radiofrequency
      energy delivery in this study and in other areas of medicine, human studies to
      assess the effect of radiofrequency energy on gastroesophageal reflux disease are
      warranted.

PMID- 10882971
TI  - Endoscopic features of smooth muscle tumors in children with AIDS.
AB  - BACKGROUND: Smooth muscle tumors are the second most common malignancy
      encountered in children with acquired immunodeficiency syndrome (AIDS). This
      study reviewed the incidence and endoscopic appearance of smooth muscle tumors in
      the gastrointestinal tract of children with AIDS undergoing endoscopy. METHODS:
      Retrospective review of all endoscopic records (n = 70) of children with AIDS
      from August 1988 to December 1997 at a tertiary care inner city hospital.
      RESULTS: Three children with advanced AIDS (4%) were found to have smooth muscle
      tumors, all of which had the typical appearance of submucosal nodules with
      central ulceration. Some were hemorrhagic. They measured less than 1 to 4 cm in
      diameter. Two children had multiple tumors. All lesions except for one were
      located in the colon. Colonic biopsies revealed a leiomyoma in one patient and a
      smooth muscle tumor of uncertain malignant potential in another. The forceps
      biopsy of the single gastric mass was not deep enough to make the diagnosis of a
      smooth muscle tumor. A nonmalignant smooth muscle tumor grew from less than 5 mm
      to more than 4 cm in 1 year and was removed surgically. All three children are
      alive without any evidence of local spread or distant metastases despite no
      specific therapy for the smooth muscle tumor. CONCLUSIONS: Smooth muscle tumors
      in the GI tract of children with AIDS are relatively common. Further study of the
      long-term outcome for children infected with the human immunodeficiency virus who
      have these lesions are needed to establish prognosis and management guidelines.

PMID- 10882972
TI  - Clinical application of the peroral electronic pancreatoscope for the
      investigation of intraductal mucin-hypersecreting neoplasm.

PMID- 10882973
TI  - Severe Mallory-Weiss tear after endoscopy treated by endoscopic band ligation.

PMID- 10882974
TI  - Massive GI bleeding due to a duodenal arteriovenous malformation.

PMID- 10882975
TI  - A case of huge gastric varices successfully treated with endoscopic injection
      sclerotherapy with occlusion of both supplying and draining veins with balloons.

PMID- 10882976
TI  - Intestinal intussusception caused by a jejunal Dieulafoy lesion.

PMID- 10882977
TI  - Colonoscopic sclerotherapy of ileal varices.

PMID- 10882978
TI  - Inverted colonic diverticulum: a rare finding in a common condition?

PMID- 10882979
TI  - Inverted hyperplastic polyp diagnosed accurately by magnifying colonoscopy.

PMID- 10882980
TI  - A large juvenile polyp in a 1-year-old child safely removed by colonoscopic
      polypectomy with a detachable snare.

PMID- 10882981
TI  - Endoscopic therapy of NSAID-induced colonic diaphragm disease: two cases and a
      review of published reports.

PMID- 10882982
TI  - Easy removal of migrated self-expanding esophageal metal stent using an endoloop
      device.

PMID- 10882983
TI  - Modification of a latex glove for the safe endoscopic removal of a sharp gastric
      foreign body.

PMID- 10882984
TI  - Appendiceal intussusception with adenocarcinoma mimicking a cecal polyp.

PMID- 10882985
TI  - Imaging of the colonoscope: magnetic, fluoroscopic, or neither?

PMID- 10882986
TI  - Endoscopic therapy for pancreatic disease: are we breaking the third rule of
      surgery?

PMID- 10882987
TI  - The color of gallstones: yellow, brown or black. Present features of Korean
      gallstone disease.

PMID- 10882988
TI  - Comment

PMID- 10882989
TI  - Difficulties in differentiating endoscopically primary from secondary gastric non
      Hodgkin's lymphoma.

PMID- 10882990
TI  - Helicobacter pylori and bleeding peptic ulcer: do we really need a gold standard?

PMID- 10882991
TI  - Response to: helicobacter pylori and bleeding peptic ulcer: Do we really need a
      gold standard?

PMID- 10882992
TI  - Predicting of hyperplastic histology by endoscopic features.

PMID- 10882993
TI  - Cell death in vasculitic neuropathy.
AB  - Vasculitic neuropathy shows cluster of differentiation (CD)4+ and CD8+
      perivascular infiltrates. CD8+ cells kill the target by different ways. Some
      mechanisms require the release of granzymes and T-cell restricted intracellular
      antigen (TIA-1) which induce cell death by apoptosis. A nonsecretory ligand
      mediated mechanism has been proposed for apoptosis and requires the interaction
      of Fas and Fas-ligand. We studied apoptosis by immunohistochemistry and terminal
      deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) in nerve biopsy
      specimens in 19 cases of vasculitic neuropathy and 8 controls. In vasculitic
      neuropathy, perivascular mononuclear cells expressed TIA-1, granzyme A, and
      granzyme B. Regarding the ligand-mediated mechanism, we observed Fas+ and Fas
      ligand+ mononuclear cells in an epineurial-perivascular distribution. Cells
      undergoing apoptosis, as demonstrated by TUNEL, represented mononuclear cells. In
      vasculitic neuropathy, apoptosis by both a secretory and a nonsecretory mechanism
      is suspected. However, apoptosis seems to be restricted to inflammatory
      mononuclear cells, suggesting that it may play a critical role in recovery from
      vasculitic neuropathy.

PMID- 10882994
TI  - Magnetic stimulation-induced modulations of motor unit firings extracted from
      multi-channel surface EMG.
AB  - The noninvasive assessment of motor unit (MU) firing patterns on the basis of
      topographical information from 128-channel high-density surface electromyography
      (SEMG) is reported. First, multi-channel MU action potential (MUAP) templates are
      obtained by clustering detected firing events according to the surface topography
      of the MUAP. Second, a template-matching algorithm is used to find all firings of
      a MU, including the superimpositions of MUAPs. From a single recording, the
      firing pattern of up to five MUs could be derived. The modulation of MU firing by
      transcranial magnetic stimulation was analyzed in peri-stimulus time histograms.
      The results are similar to previous results of transcranial magnetic stimulation
      (TMS) obtained by needle electromyographic (EMG) recordings. The method can be
      used to investigate MU firing patterns in patients with central motor disorders.
      An additional advantage of the technique, apart from its noninvasiveness, is the
      structural and functional information that it provides on the MUs, which is not
      obtained by needle EMG.

PMID- 10882995
TI  - New transthyretin mutation V28M in a Portuguese kindred with amyloid
      polyneuropathy.
AB  - A 62-year-old Portuguese man, with no history of familial amyloid polyneuropathy
      (FAP), and a 2(1/2)-year history of tingling in the toes and sexual dysfunction
      was found neurophysiologically to have a sensory-motor axonal polyneuropathy.
      Autonomic tests showed slight sympathetic and marked parasympathetic involvement.
      Heart, kidney, and eyes were normal. Single strand conformation polymorphism
      (SSCP) mutation analysis for the transthyretin (TTR) gene was performed. The SSCP
      pattern suggested the presence of a mutation in exon 2, but was different from
      the pattern observed for a control representing the most common TTR mutation
      associated with FAP, i.e., TTR V30M. DNA sequencing analysis revealed an A-to-G
      transition in the first base of codon 28 normally encoding a valine, giving rise
      to a methionine residue. The presence of this extra methionine was confirmed by
      peptide mapping and mass spectrometry analysis. Biopsy of nerve and skin of the
      propositus showed amyloid deposits that were immunoreactive for TTR. This is a
      new variant TTR related to late-onset amyloid neuropathy with autonomic
      dysfunction. This case confirms that TTR mutation screening should be considered
      in patients with a clinical disorder consistent with amyloid neuropathy even in
      the absence of a family history.

PMID- 10882996
TI  - Quantification of jiggle in real electromyographic signals.
AB  - Two parameters have been defined for quantifying jiggle: normalized consecutive
      amplitude differences (CAD) and the cross-correlational coefficient of
      consecutive discharges (CCC). In real recordings, artifacts from several sources
      may increase the variability of these parameters as they were originally defined.
      Two methodological modifications designed to overcome such a limitation are
      proposed: estimation of baseline fluctuation from segments of the recording free
      from nearby concurrent motor unit potentials (MUPs), and waveform alignment of
      consecutive discharges by correlation maximization (CM). The results obtained by
      the original and modified methods were compared for MUPs from normal subjects and
      patients with amyotrophic lateral sclerosis and chronic neurogenic diseases. With
      the modified method, CAD and CCC showed fewer extreme values and less scatter.
      The number of successfully aligned MUPs with the CM method was 18.8% higher (n =
      394; Chi-square = 54.6; P < 0.001), including irregular and unstable MUPs. The
      proposed modifications improve our capability to quantify the jiggle of real
      signals and reduce the necessity of manual interventions although low
      interference recordings and operator supervision are still required.

PMID- 10882997
TI  - Anti-GQ1b antibodies and evoked acetylcholine release at mouse motor endplates.
AB  - Miller Fisher syndrome (MFS) is clinically characterized by ataxia, areflexia,
      and ophthalmoplegia, and is associated with serum anti-GQ1b-ganglioside
      antibodies. We have previously shown that anti-GQ1b antibodies induce complement
      dependent, alpha-latrotoxin-like effects at mouse neuromuscular junctions (NMJs)
      in vitro. This effect comprises a massive increase in spontaneous quantal
      acetylcholine (ACh) release, accompanied by block of evoked release and muscle
      paralysis. This mechanism may contribute to the motor features of MFS. Whether
      the block of evoked ACh release is a primary effect of anti-GQ1b antibodies or
      occurs secondary to massive complement-dependent spontaneous release is unknown.
      Using conventional micro-electrode methods, we measured in detail ACh release
      evoked with low- and high-rate nerve stimulation, and studied the effect on it of
      a purified MFS IgG and a mouse monoclonal anti-GQ1b IgM (without added
      complement). We found that evoked transmitter release was unaffected. Control
      experiments proved binding of anti-GQ1b antibody at the NMJ. We conclude that the
      block of nerve-evoked ACh release at the NMJ is not a primary effect of anti-GQ1b
      antibodies, but is dependent on antibody-mediated complement activation. It
      remains to be determined whether the block of nerve-evoked ACh release is the
      consequence of massive spontaneous ACh release or occurs as a concomitant event.

PMID- 10882998
TI  - Further evidence for corticomotor hyperexcitability in amyotrophic lateral
      sclerosis.
AB  - A collision experiment has been used to investigate repetitive firing of first
      dorsal interosseous motoneurons following a single transcranial magnetic stimulus
      (TMS) in healthy subjects and patients with amyotrophic lateral sclerosis (ALS).
      An appropriately timed supramaximal peripheral nerve shock blocks the first
      descending impulses in the motor axons and allows the response due to repetitive
      firing to be quantified. Multiple firing of motoneurons in healthy subjects
      increases as TMS intensity rises and saturates at about 1.25 times threshold.
      Increasing background force also augments repetitive firing and saturates at
      force levels above 50% maximum. The ratio of the area of the response attributed
      to repetitive motoneuron firing to the area of the initial direct response to TMS
      was compared in 10 ALS patients and 10 healthy controls. In ALS patients, the
      ratio was significantly higher (P = 0. 0005), indicating a greater degree of
      repetitive firing of motoneurons. This suggests that, in ALS, there is
      corticomotor hyperexcitability either at the spinal motoneuron or motor cortex.

PMID- 10882999
TI  - Highly concentrated vascular endothelial growth factor in platelets in Crow
      Fukase syndrome.
AB  - We report a marked difference in concentration of vascular endothelial growth
      factor (VEGF) between serum and plasma in patients with Crow-Fukase syndrome
      (CFS). The serum/plasma VEGF levels in 4 CFS patients were 8,634/152, 5,203/176,
      3,724/127, and 868/13 pg/ml, respectively. We also showed that platelets were a
      major source of this VEGF and that VEGF was released during platelet aggregation
      by physiological stimulation. It is suggested that in CFS, local VEGF
      concentration is markedly elevated by aggregation of platelets containing
      excessive VEGF and their adhesion to vascular walls, resulting in excessive
      physiological activities of VEGF. Our findings provide important information for
      developing more effective therapeutic trials.

PMID- 10883000
TI  - Analysis of motor unit firing patterns in patients with central or peripheral
      lesions using singular-value decomposition.
AB  - We applied the singular value decomposition (SVD) method to study single motor
      unit firing patterns. Two projects were carried out: (1) a computer simulation
      study to confirm the meanings of two SVD parameters, the eigenvalue corresponding
      to the positive-slope eigenvector (PEV) and that corresponding to the negative
      slope eigenvector (NEV); and (2) a clinical study for which electromyographic
      (EMG) recordings were made from first dorsal interosseous muscle in patients with
      stroke, myopathies, or neuropathies and in healthy control subjects. Results of
      computer simulation reveal that the NEV reflects the amount of instantaneous
      firing variability, whereas the PEV/NEV (P/N) ratio exhibits the relative effect
      of a trend in the firing pattern. In human studies, the P/N ratio of stroke
      patients was significantly higher than that of the controls, whereas their NEV
      was comparable. By contrast, in the myopathy and neuropathy groups, the NEV
      increased significantly, whereas the P/N ratio did not. These results suggest
      that the SVD method decomposes the motor unit (MU) firing variation into two
      components and that the mechanism for increased firing variability is different
      for supraspinal and spinal-infraspinal lesions.

PMID- 10883001
TI  - Mitochondrial myopathy and familial thiamine deficiency.
AB  - We studied two siblings with a mitochondrial myopathy, familial thiamine
      deficiency, and an A3243G mutation of the mitochondrial DNA (mtDNA). The elder
      brother (patient 1, now 36 years old) developed myopathy and beriberi heart at 20
      years of age. Thiamine therapy resolved the cardiac symptoms and hyperpyruvicemia
      and improved the myopathy. The younger brother presented aged 19 years with a
      myopathy (patient 2, now 35 years old). Thiamine deficiency was present in the
      siblings and parents, and ragged-red fibers (RRFs) were noted in muscle biopsies
      from the siblings. Analysis 17 years later demonstrated thiamine malabsorption
      and an A3243G mutation of the mtDNA in both siblings and their mother,
      progressive myopathy, and an increased number of RRFs and elevated serum CKMB
      activity in patient 1. Thiamine treatment decreased the serum concentrations of
      lactate and pyruvate in patient 2, but not patient 1. The role of thiamine in
      mitochondrial dysfunction caused by an electron transfer disorder in the setting
      of A3243G mtDNA mutation is discussed.

PMID- 10883002
TI  - Motor unit sound in needle electromyography: assessing normal and neuropathic
      units.
AB  - Motor unit action potentials (MUPs) recorded by a monopolar needle electrode in
      normal and neuropathic muscles were computer-simulated. Five experienced
      electromyographers acted as examiners and assessed the firing sounds of these
      MUPs without seeing them on a display monitor. They judged whether the sounds
      were crisp or close enough to accept for the evaluation of MUP parameters and
      whether, when judged acceptable, they were neuropathic-polyphasic. The examiners
      recognized motor unit (MU) sound as crisp or polyphasic when the MUP obtained was
      0.15-0.2 mm from the edge of the MU territory. When the intensity of the sound
      decreased, they were unable to perceive it as crisp. When the intensity exceeded
      the saturation level of loudspeaker output, the sound was perceived as
      polyphasic, but the wave form of the MUP was not. When the frequency of the
      neuropathic MUP was lowered, the examiners were unable to determine whether the
      MUP was polyphasic. MUPs recognized as acceptable for evaluation can be
      distinguished by listening to MU sounds. The audio amplifier gain must be
      appropriately adjusted for each MUP amplitude in order to assess whether an
      individual MU sound is crisp or polyphasic before MUP parameters are measured on
      a display monitor.

PMID- 10883003
TI  - Endothelium-dependent vasodilatation in patients with familial amyloidotic
      polyneuropathy.
AB  - We examined endothelium-dependent vasodilatation in 15 familial amyloidotic
      polyneuropathy (FAP) amyloidogenic transthyretin (ATTR) Valine30Methionine
      (Val30Met) patients and 12 healthy volunteers. Using ultrasonography, we measured
      the radial artery diameters under both baseline and hyperemic conditions.
      Endothelium-dependent vasodilatation was expressed as a percent increase in the
      diameters of the radial artery after induced hyperemia. Endothelium-dependent
      vasodilatation tended to decrease in the patients, compared with healthy
      volunteers. Responses were not elicited at all in patients with disease of more
      than 9 years' duration. Linear negative correlation was observed between
      endothelium-dependent vasodilatation and disease duration (P < 0.01). Correlation
      between endothelium-dependent vasodilatation and degree of autonomic dysfunction
      was significant (P = 0.0524) and for age was close to significance (P = 0.051).
      These results suggest that the peripheral vasomotor dysfunction in FAP patients
      may predominantly depend on the amount of amyloid deposition around the vessels
      through the course of illness.

PMID- 10883004
TI  - Exercise test in muscle channelopathies and other muscle disorders.
AB  - We studied the percentage change in compound muscle action potential (CMAP)
      amplitude and area during and after a 5-min maximal contraction of the muscle.
      The exercise test (ET) was performed on 64 patients with different muscle
      disorders and on 46 normal controls. The range of normal ET values was defined as
      the mean + 2 SD of the control values. The mean sensitivity of the test was 63%
      in the whole group with ion channel muscle disorders, the highest sensitivity
      being seen in primary periodic paralysis (81%) and the lowest in chloride
      channelopathies (17%). In thyrotoxic periodic paralysis, the ET was abnormal in
      the three of the four patients studied. In patients with myotonic dystrophy, a
      smaller than normal increase in CMAP amplitude occurred during and after
      exercise, whereas in proximal myotonic myopathy a normal initial increase in CMAP
      amplitude was followed by an abnormal decrement. We conclude that the ET can be
      of use in confirming abnormal muscle membrane excitability in patients with
      calcium and sodium channelopathies and thyrotoxic periodic paralysis. In chloride
      channelopathy, the test may also be abnormal, but shows no, or only a small,
      increase in amplitude or area in the immediate postexercise period. The test may
      also be abnormal in proximal myotonic myopathy, but is normal in myotonic
      dystrophy.

PMID- 10883005
TI  - Myosin heavy chain IIX overshoot in human skeletal muscle.
AB  - The distribution of myosin heavy chain (MHC) isoforms, fiber type composition,
      and fiber size of the vastus lateralis muscle were analyzed by sodium
      dodecylsulfate polymerase gel electrophoresis (SDS-PAGE), ATPase histochemistry,
      and immunocytochemistry in a group of adult sedentary men before and after 3
      months of heavy-load resistance training and, subsequently, after 3 months of
      detraining. Following the period of resistance training, MHC IIX content
      decreased from 9.3 +/- 2.1% to 2.0 +/- 0.8% (P < 0.01), with a corresponding
      increase in MHC IIA (42.4 +/- 3.9% vs. 49.6 +/- 4.0% [P < 0.05]). Following
      detraining the amount of MHC IIX reached values that were higher than before and
      after resistance training (17.2 +/- 3.2% [P < 0.01]). Changes in fiber type
      composition resembled the changes observed in MHC isoform content. Significant
      hypertrophy was observed for the type II fibers after resistance training.
      Maximal isometric quadriceps strength increased after resistance training, but
      returned to pretraining levels after detraining. The present results suggest that
      heavy-load resistance training decreases the amount of MHC IIX while reciprocally
      increasing MHC IIA content. Furthermore, detraining following heavy-load
      resistance training seems to evoke an overshoot in the amount of MHC IIX to
      values markedly higher than those observed prior to resistance training.

PMID- 10883006
TI  - Skin and muscle vasomotor reflexes in detecting autonomic dysfunction in leprosy.
AB  - There are few tests to assess the function of small unmyelinated nerve fibers.
      One established test is the skin vasomotor reflex (SVMR), which uses laser
      doppler flow velocimetry. The SVMR has the disadvantages of being susceptible to
      interference (from change of temperature and alerting stimuli) and of requiring
      expensive equipment. An ultrasound doppler method, which is less expensive, can
      be used to detect muscle vasomotor reflex (MVMR) activity. We sought to compare
      the efficacy of these two methods in detecting dysfunction of small unmyelinated
      nerve fibers in patients with leprosy. SVMR was shown to be less sensitive (P <
      0.01) and specific (P < 0.001) than MVMR. The favorable results of MVMR may be
      attributed to its lesser susceptibility to interfering sympathetic
      vasoconstriction from alerting stimuli. MVMR also reflects larger areas of blood
      vessel innervation than the laser doppler method. In leprosy, nerve damage is
      typically patchy and may be missed by the smaller sampling of the laser method.

PMID- 10883008
TI  - Electrodiagnostic significance of supramaximally stimulated A-waves.
AB  - A-waves are generally considered a nonspecific finding of unclear
      electrodiagnostic and clinical significance. We systematically identified A-waves
      during routine F-wave studies and defined them as supramaximally elicited
      reproducible intermediate to late responses that are clearly separate from the M
      responses. In patients with A-waves, we noted electrophysiologic diagnoses, the
      nerve in which the A-wave was identified, the presence of A-waves in multiple
      nerves, and A-wave morphology. In 54 of 1,258 studies performed, A-waves were
      present in one or more nerves. Electrophysiologic diagnoses in patients with A
      waves included diffuse axonal neuropathy (11.5%), demyelinating neuropathy
      (66.7%), motor neuron disease (6.5%), radiculopathy (3.6%), mononeuropathy
      (3.9%), and normal (tibial nerve only) 0.7%. A-waves were abnormal when found in
      any nerve except the tibial nerve. They were particularly prevalent and present
      in multiple nerves in acquired and hereditary demyelinating neuropathies, and
      they more often had a complex morphology. We postulate that demyelination is the
      crucial underlying pathophysiologic correlate of the supramaximally stimulated A
      wave.

PMID- 10883007
TI  - Muscle CT scan findings in McLeod syndrome and chorea-acanthocytosis.
AB  - Computed tomography (CT) scans of lower leg muscles reveal a selective pattern of
      fat infiltration in the posterior compartment with spared gracilis,
      semitendinosus, and the lateral head of the gastrocnemius in both McLeod syndrome
      and chorea-acanthocytosis, which are disorders characterized by the presence of
      circulating acanthocytes. The selectivity of affected muscles indicates that late
      onset and slowly progressive muscular atrophy in both diseases could be a
      consequence of primary myopathy. Asymmetrical muscle involvement may be seen
      during the process of degeneration only in McLeod syndrome, however, and may be
      helpful in distinguishing this disease from chorea-acanthocytosis.

PMID- 10883009
TI  - Sensory nerve conduction study of the mental nerve.
AB  - We describe a technique for sensory nerve conduction study of the mental nerve. A
      monopolar recording needle is placed near the mandibular foramen using the same
      approach as that for routine inferior alveolar nerve block in dentistry, and a
      surface reference electrode is positioned over the ipsilateral mastoid process.
      Sensory nerve action potentials to stimulation of the mental nerve at the chin
      can be reliably recorded orthodromically in normal healthy subjects. The method
      is simple and well tolerated and provides a useful means to evaluate mental nerve
      function electrophysiologically.

PMID- 10883010
TI  - Effects of transcranial magnetic stimulation on results of the twitch
      interpolation technique.
AB  - To investigate whether transcranial magnetic stimulation (TMS) has an effect on
      isometric muscle force elicited by maximal voluntary contractions (MVC) and the
      ability to activate a muscle voluntarily (VA, as a percentage of full muscle
      activation), a twitch-interpolation technique was applied on the quadriceps
      femoris muscles of six volunteers before and within 1 min after TMS. VA improved
      by 5% (P = 0.019) and MVC by 17% (P = 0.002), whereas these parameters were
      unchanged in a control experiment. The results suggest that TMS has an effect on
      the central motor drive, at least within 1 min after stimulation.

PMID- 10883011
TI  - Congenital myasthenic syndrome with sleep hypoventilation.
AB  - We report the case of a 13-year-old boy with acetylcholinesterase deficiency, a
      congenital myasthenic syndrome, who developed sleep hypoventilation syndrome
      during a period of rapid growth. His symptoms were insidious and life-threatening
      despite changes in strength or lung volume measurements that were not marked. He
      responded well to noninvasive nocturnal ventilation, with reversal of symptoms
      and normalization of blood gases. His lung volumes, but not motor function,
      improved after treatment.

PMID- 10883012
TI  - Granulomatous myositis, primary biliary cirrhosis, pancytopenia, and thymoma.
AB  - Granulomatous myopathies are rare. Most cases are associated with sarcoidosis. We
      report a case of granulomatous myopathy associated with primary biliary
      cirrhosis, pancytopenia, and thymoma. The literature in regard to granulomatous
      myopathy and its pathogenesis is reviewed. Intermittent pulsed intravenous
      methylprednisolone may be useful as maintenance therapy for granulomatous
      myopathy and other neuromuscular syndromes for patients intolerant of oral
      corticosteroids.

PMID- 10883013
TI  - AAEM case report 16. Botulism. American Association of Electrodiagnostic
      Medicine.
AB  - Early diagnosis of botulism is essential for effective treatment.
      Electrophysiologic testing can be of major help to establish a prompt diagnosis,
      but the classic electrodiagnostic features of botulism are often elusive.
      Decrement or increment of compound muscle action potential (CMAP) amplitudes to
      slow or fast rates of nerve stimulation are often unimpressive or totally absent.
      Reduction of CMAP amplitudes, denervation activity, or myopathic-like motor unit
      potentials in affected muscles are found more frequently but they are less
      specific. In general, the electrophysiologic findings taken together suggest
      involvement of the motor nerve terminal, which should raise the possibility of
      botulism. The case reported here illustrates a common clinical presentation of
      botulism. This study emphasizes realistic expectations of the electrodiagnostic
      testing, the differential diagnosis, and the potential pitfalls often encountered
      in the interpretation of the electrophysiologic data.

PMID- 10883015
TI  - Reply

PMID- 10883016
TI  - AAEM news and comments

PMID- 10883014
TI  - Influence of intrathecal baclofen on silent periods in dystonia.

PMID- 10883017
TI  - Ovarian cancer.

PMID- 10883018
TI  - Ovarian cancer: epidemiology, biology, and prognostic factors.
AB  - Ovarian cancer varies widely in frequency among different geographic regions and
      ethnic groups, with a high incidence in Northern Europe and the United States,
      and a low incidence in Japan. The majority of cases are sporadic, and only 5% to
      10% of ovarian cancers are familial. The etiology of ovarian cancer is poorly
      understood. Models of ovarian carcinogenesis include the theory of incessant
      ovulation, in which a person's age at ovulation, i.e., lifetime number of
      ovulatory cycles, is an index of her ovarian cancer risk. Excessive gonadotropin
      and androgen stimulation of the ovary have been postulated as contributing
      factors. Exposure of the ovaries to pelvic contaminants and carcinogens may play
      a role in the pathogenesis of ovarian cancer. Epidemiologic and molecular-genetic
      studies identify numerous risk and protective factors. The most significant risk
      factor is a family history of the disease. Recent advances in molecular genetics
      have found mutations in the BRCA1 and BRCA2 tumor suppressor genes responsible
      for the majority of hereditary ovarian cancer. Additional risk factors include
      nulliparity and refractory infertility. Protective factors include multiparity,
      oral contraceptives, and tubal ligation or hysterectomy. With five years of oral
      contraceptive use, women can cut their risk of ovarian cancer approximately in
      half; this also holds true for individuals with a family history. Stage at
      diagnosis, maximum residual disease following cytoreductive surgery, and
      performance status are the three major prognostic factors. Using a multimodality
      approach to treatment, including aggressive cytoreductive surgery and combination
      chemotherapy, five-year survival rates are as follows: Stage I (93%), Stage II
      (70%), Stage III (37%), and Stage IV (25%).

PMID- 10883019
TI  - Current management of epithelial ovarian carcinoma: a review.
AB  - Epithelial carcinoma of the ovary is the most lethal of gynaecological
      malignancies and it affects about one in 70 women in developed countries. Over
      75% of women with the disease have tumour spread beyond the pelvis at the time of
      diagnosis, and their treatment requires the appropriate use of surgery and
      chemotherapy. The strategies used in the treatment of ovarian cancer are
      constantly evolving. An overview of current treatment regimens and their
      evolution is provided, with particular emphasis on the interdependence of surgery
      and chemotherapy in the optimal management of the disease.

PMID- 10883020
TI  - Prophylactic oophorectomy: clinical considerations.
AB  - Ovarian cancer usually remains clinically silent until it is far advanced, and is
      associated with significant morbidity and mortality. In view of the modest impact
      of adjuvant treatments on survival, much effort is devoted to early detection
      programs and prevention strategies. However, the usefulness of early detection
      programs remains to be established, with only one randomized study indicating
      improved median survival in screened individuals. At present, oral contraceptives
      and prophylactic oophorectomy are the only options for prevention of ovarian
      cancer. Indications for prophylactic oophorectomy either as a primary procedure,
      or secondary to abdominal surgery, will vary according to the estimated risk, and
      to the individual's perception of that risk. Genetic screening allows better
      identification of pre-symptomatic individuals who would benefit the most from
      prophylactic oophorectomy. Data concerning the benefit of prophylactic surgery,
      and the safety of established or innovative hormone replacement therapies in
      individuals at risk, are encouraging.

PMID- 10883021
TI  - Management of adnexal masses: role and risk of laparoscopy.
AB  - Laparoscopic surgery has become the gold standard in the treatment of benign
      adnexal masses, whereas laparotomy remains the standard for the treatment of
      malignant tumors. The laparoscopic management of adnexal masses remains
      controversial because of the potential risks of cancer dissemination suggested by
      many case reports and national surveys. Experimental data show potential
      advantages and disadvantages for the laparoscopic treatment of gynecologic
      cancer. Since the risk of dissemination appears high when a large number of
      malignant cells are present, adnexal tumors with external growths and bulky lymph
      nodes may be considered contra-indications to CO(2) laparoscopy. Surgical
      diagnosis is the key to adequate management of adnexal masses. In our experience,
      laparoscopic diagnosis of malignancy is reliable after a careful pre-operative
      evaluation has been performed. Moreover, national surveys have revealed that
      despite suspicious laparoscopic findings, many malignant masses were considered
      benign at the outset. Using strict guidelines, laparoscopic diagnosis can be
      proposed for both non-suspicious and complex masses, thus avoiding many
      unnecessary laparotomies for benign masses suspicious at ultrasound. The more
      controversial limits of laparoscopic treatment are discussed. If a laparotomy was
      performed for all masses suspicious at surgery, 80% of the cases would be treated
      by laparoscopy. The role of laparoscopy for restaging and second-look operations
      for ovarian cancer requires further evaluation.

PMID- 10883022
TI  - Surgical staging of early invasive epithelial ovarian tumors.
AB  - Early stage epithelial ovarian carcinoma is defined pathologically as a tumor
      strictly limited to one or both ovaries without any extra-ovarian disease (i.e.,
      Stage IA or B of the International Federation of Gynecology and Obstetrics (FIGO)
      classification). This diagnosis can be obtained only after an exhaustive surgical
      staging procedure, performed as soon as the diagnosis of epithelial invasive
      ovarian carcinoma is established. This staging surgery currently encompasses a
      peritoneal cytology, the thorough inspection of all the visceral and parietal
      peritoneal surfaces with biopsy of any abnormality, total abdominal hysterectomy
      and bilateral salpingo-oophorectomy (TAH + BSO), random peritoneal biopsies,
      omentectomy, appendectomy and bilateral pelvic and para-aortic lymphadenectomies,
      up to the left renal vein. The results of this staging procedure and its
      indications are discussed. In all of the cases, the radical removal of the
      pathologic adnexa is indicated, along with the complete peritoneal and
      retroperitoneal staging. While fertility-sparing surgery (avoiding hysterectomy
      and contralateral adnexectomy, if possible) seems to be safe for young women, a
      TAH + BSO is the rule for the others. Adjuvant chemotherapy can be omitted in
      well-differentiated tumors with a negative staging operation, but currently it
      remains indicated in all other cases. Indeed, the ultimate goal in early stage
      ovarian carcinoma is to not impair by inadequate management the high chance of a
      cure.

PMID- 10883023
TI  - Cytoreductive surgery for advanced stages of ovarian cancer.
AB  - During the past two decades, maximum cytoreductive surgery (also called debulking
      surgery) has been the recommended surgical approach for advanced stages of
      ovarian carcinoma. The residual tumor volume after surgery is one of the
      strongest prognostic factors, and only patients who undergo complete or optimal
      surgery are likely to be long-term survivors (i.e., 50% after five years). A well
      trained surgeon in the field of gynecologic oncology can achieve an optimal tumor
      reduction in up to 75% of patients with advanced stage ovarian cancer. During the
      procedure, bowel resection, especially rectosigmoid, must be undertaken in 30% to
      40% of cases, and para-aortic and pelvic lymphadenectomy should be performed
      after adequate tumor reduction in the abdominal cavity. The experienced surgeon
      can perform these surgeries with an acceptable morbidity, allowing chemotherapy
      to be undertaken within the month following surgery. However, very advanced
      cancer with massive peritoneal carcinomatosis and/or Stage IV disease requires a
      very aggressive surgical procedure but yields a poor prognosis and a higher risk
      of unacceptable complications. For these worst cases, the concept of
      cytoreductive surgery is moving toward the alternative strategy of chemosurgical
      cytoreduction, in which interval cytoreductive surgery is undertaken after three
      cycles of front-line chemotherapy. The goal of this experimental strategy is to
      achieve a complete tumor response after front-line chemosurgical therapy, and a
      better quality of life.

PMID- 10883024
TI  - Interval debulking surgery: an alternative for primary surgical debulking?
AB  - Retrospective analyses suggest that a subgroup of patients with Stage III and IV
      ovarian carcinoma can be treated with neo-adjuvant chemotherapy followed by
      interval debulking surgery. The absolute indications for neo-adjuvant
      chemotherapy appear to be Stage IV disease (excluding pleural fluid) or
      metastases of more than 1 g at sites where resection is impossible. In patients
      with an estimated total metastatic tumor load of >100 g, the presence of at least
      two of the following relative indications for neo-adjuvant chemotherapy are
      considered to be necessary: 1) uncountable (>100) peritoneal metastases, 2)
      estimated metastatic tumor load of >1000 g, 3) presence of large (>10 g)
      peritoneal metastatic plaques, 4) large volume ascites, and 5) World Health
      Organization (WHO) status II or III. Interval debulking surgery in patients with
      suboptimal primary debulking surgery has been proven effective in increasing
      overall survival and progression-free survival in a large prospective, randomized
      trial of the European Organization for Research and Treatment of Cancer (EORTC).
      The strategy of neo-adjuvant chemotherapy, followed by interval debulking
      surgery, should be confirmed in a prospective randomized trial. The EORTC 55971
      trial is currently addressing this issue. We will review the studies on primary
      chemotherapy, interval debulking surgery, and the indications for primary
      chemotherapy followed by interval debulking surgery, and ongoing trials.

PMID- 10883025
TI  - Second-look and second surgery: second chance or second best?
AB  - About 40 years ago, second-look laparotomy (SLL) was introduced to evaluate,
      surgically and pathologically, primary treatment in case a clinical complete
      remission was obtained in ovarian cancer patients. But does SLL increase the
      disease-free or overall survival? Important technical aspects of the procedure
      as: how many biopsies should be taken, can laparoscopy be replaced by laparotomy
      and should complete lymphadnectomy be performed at SLL, are still not clarified.
      This and maybe even more important issues, are disputed in literature: for
      instance, should a SLL be done at all, or should a SLL be performed in order to
      do a secondary cytoreduction in case tumour is found at the operation. If
      clinical remission is reached in more than 50% of the patients with advanced
      disease, tumour still can be found at SLL. If no tumour is found at SLL,
      macroscopically or microscopically, the operation is redundant. Apart from this,
      the recurrence rate after such a "negative SLL" is about 35%. Whether tumour
      found at SLL should be removed will depend on the fact if the tumour still is
      responsive to chemotherapy. To minimise the chance of tumour resistance,
      secondary surgery should be done as early as possible during treatment.
      Therefore, an interval debulking will be the intervention of choice. So, as long
      as there is no evidence that SLL increases the survival in ovarian cancer
      patients, it should be done in a research setting only. Also, the usefulness of
      secondary surgery for recurrent disease mainly depends on the chemo-sensitivity
      of the tumour. After a complete remission, which lasts for more than a year,
      complete secondary cytoreduction, again followed by chemotherapy, improves
      survival.

PMID- 10883026
TI  - Recurrent ovarian carcinoma: is there a place for surgery?
AB  - The role of cytoreductive surgery is well established in patients with primary
      ovarian carcinoma. Minimal residual disease translates to improved response to
      adjuvant treatment and prolonged survival. For close clinical follow-up,
      different approaches may be helpful in detecting recurrent disease, including
      regular physical/pelvic examination, serial CA-125 levels, and imaging studies
      using computerized tomography, magnetic resonance imaging, or positron emission
      testing. At recurrence, those patients with a good performance status, a good
      response to primary therapy, and a macronodular tumor distribution pattern may be
      candidates for a secondary cytoreductive procedure. Data suggests that secondary
      cytoreduction is superior to chemotherapy alone in patients who have a
      significant disease-free interval (6 to 12 months). Survival after secondary
      cytoreduction is optimized with cytoreduction to microscopic disease, yet there
      is a recognized risk of surgical morbidity. Therefore, a strong relationship
      between the gynecologic oncology surgeon and the patient is key to obtaining
      appropriate informed consent and relaying appropriate outcome expectations.

PMID- 10883027
TI  - Surgery for borderline tumor of the ovary.
AB  - The five-year survival for women with Stage I borderline tumors is about 95% to
      97%, but because of late recurrence the 10-year survival is only 70% to 95%. The
      five-year survival for Stage II-III patients is 65% to 87%. A more correct
      staging procedure, classification of true serous implants, and agreement on how
      the presence of gelatinous ascites in mucinous tumors contributes to cancer stage
      might change the distribution of stage and survival data by stage for women with
      borderline tumors in the future. Independent prognostic factors for patients with
      borderline tumors without residual tumor after primary surgery are: DNA ploidy,
      morphometry, International Federation of Gynecology and Obstetrics (FIGO) stage,
      histologic type, and age. Different types of surgery and chemotherapy were not
      independent prognostic factors. Questions which should be addressed include the
      following: 1) Have patients with borderline tumors been over treated in general,
      and how should these patients be treated? 2) In which group of patients is
      fertility-sparing surgery advisable? 3) Do patients with borderline tumors
      benefit from adjuvant treatment? And 4) How is the high-risk patient defined?

PMID- 10883029
TI  - [What does the word "health" mean?].

PMID- 10883028
TI  - Surgery for germ cell tumors.
AB  - We performed a review of the current modalities of surgical treatment of
      malignant ovarian germ cell tumors by clinical stages and histological types.
      Stage IA dysgerminoma is performed with a unilateral salpingo-oophorectomy (USO)
      without chemotherapy. However, for Stage IB or IC patients with dysgerminoma, USO
      plus chemotherapy as a primary treatment may or may not be followed with a second
      look operation (SLO). For non-dysgerminomas, USO is indicated only for Stage IA
      immature teratoma grade 1. The treatment for Stage IA immature teratoma grade 2
      or 3 and other histological types is USO plus chemotherapy. Patients with Stage
      IB, IC or higher with non-dysgerminoma are treated with USO plus chemotherapy or
      USO with contralateral partial ovariectomy plus chemotherapy. For patients who
      require non-conservative surgery, a total abdominal hysterectomy (TAH) and a
      bilateral salpingo-oophorectomy (BSO) plus chemotherapy are performed. For
      patients with Stage II of all histological types, conservative surgery consists
      of USO and a cytoreductive operation plus chemotherapy, followed by SLO or a
      second cytoreductive operation. For non-conservative surgery, TAH+BSO with or
      without a cytoreductive operation plus chemotherapy is followed by SLO.
      Conservative surgery for patients with Stage III and IV is USO and a
      cytoreductive operation plus chemotherapy followed by a second cytoreductive
      operation. Non-conservative surgery is TAH+BSO with a cytoreductive operation
      plus chemotherapy, followed by SLO or a second cytoreductive operation. However,
      primary or secondary cytoreductive surgery with or without lymphadenectomy and
      SLO are still controversial in terms of improving patient survival.

PMID- 10883030
TI  - Social and cultural dimensions of hypertension in Brazil: a review.
AB  - Elevated arterial blood pressure varies substantially in relation to social and
      cultural variables. Early work on acculturation, socioeconomic status, and blood
      pressure documented this variation, which could not be explained entirely by
      conventional factors such as diet, physical activity, or access to medical care.
      These findings stimulated the development of a model of stress and disease. The
      stress model emphasizes social and psychological factors that are perceived by
      individuals to be stressful, as well as factors that help individuals to respond
      to those stressors. Conventional stress models are, however, problematic because
      the primary emphasis is on individual perception, with little consideration of
      the social and cultural context in which stress occurs. This paper describes a
      complementary model of social and cultural influences on disease risk, placing
      greater emphasis on how individuals are able to approximate, in their own
      behaviors, shared cultural models of life, referred to as "cultural consonance".
      Findings from research in Brazil indicate that the higher an individual's
      cultural consonance, the lower his or her blood pressure. These results indicate
      the importance of linking different levels of analysis - the cultural, the
      individual, and the biological - to understand disease risk.

PMID- 10883031
TI  - [Basic principles of statistical methods applied to public health surveillance
      data analysis: a review].
AB  - Statistical methods in public health surveillance data analysis are important for
      detecting temporal and/or spatial disease clusters, which can indicate an
      outbreak or an epidemic. In this paper we present a review and literature survey
      introducing the public health surveillance process and focusing on some
      statistical methods which are indicated to the data analysis in routine
      procedure. Comparative studies of these methods are also analyzed.

PMID- 10883032
TI  - [Genetico-epidemiological and molecular investigation of G-6-PD deficiency in a
      Brazilian community].
AB  - This paper reports on a study of the G-6-PD deficiency in Braganca Paulista, Sao
      Paulo State, Brazil. A total of 4,621 male blood donors were investigated over a
      36-month period. Of these, 80 had the G-6-PD deficiency. Molecular analysis was
      performed on 70 unrelated G-6-PD deficients through DNA amplification followed by
      digestion with restriction enzymes and single strand conformation polymorphism
      analysis (SSCP). In 98.6%, the G-6-PD A- (202 G<--A) mutation was observed
      through digestion of exon 4 with Nla III. The presence of an uncommon mutation in
      exon 9 was also observed through SSCP. No case of the Mediterranean variant was
      observed. These results indicate that the A- (202G<--A) variant, almost
      exclusive, was introduced into the community not only by individuals of African
      origin, but also by European immigrants, mainly Italian, Spanish, and Portuguese.
      The Italian contribution in terms of the G-6-PD Mediterranean variant was smaller
      than its contribution to beta thalassemia, probably due to the Northern Italian
      origin of these immigrants.

PMID- 10883034
TI  - [Long-term benzodiazepine use in women at a daycare center for older people].
AB  - While experts recommend caution against long-term benzodiazepine use in the
      elderly, survey data suggests that the use of benzodiazepine increase with age.
      The patterns of benzodiazepine use and factors associated with long-term use in
      population at risk were studied with a standarlized questionnaire applied to 634
      women over 60, who attended a daycare center for older people in Rio de Janeiro
      between May, 1992 and December, 1995. Prevalence of benzodiazepine use in the
      last 15 days was 21.3% (CI 95% 18.1-24.5), and prevalence of daily use for 12 or
      more months was 7.4% (CI 95% 5.4-9.4). In a multivaried analysis the amount of
      drugs being consumed displayed an important and progressive association with long
      term benzodiazepine use, with OR = 2.77 (CI 95% 1.17-6.57) for those who take
      from four to six drugs, and OR = 7.62 (CI 95% 3.18-18.26) for those who take more
      than seven drugs. Insomnia (OR = 8.87 CI 95% 2.53-31.06) and chronic headache (OR
      = 3.53 CI 95% 1.82-6.89) have also been associated with this pattern of use.

PMID- 10883033
TI  - The impact of multidrug therapy on the epidemiological pattern of leprosy in Juiz
      de Fora, Brazil.
AB  - We investigated the impact of multidrug therapy (MDT) on the epidemiological
      pattern of leprosy in Juiz de Fora, Brazil, from 1978 to 1995. Evaluation of
      1,283 medical charts was performed according to the treatment regimen used in two
      different periods. Following the introduction of MDT in 1987, prevalence of
      leprosy decreased from 22 patients/10,000 inhabitants to 5.2 patients/10,000
      inhabitants in 1995. Incidence rate of leprosy was lower in period II (1987-1995)
      than in period I (1978-1986). Decreasing prevalence and incidence appear to be
      related to drug efficacy rather than decreased case identification, since both
      self-referred and professionally referred treatment increased markedly from
      period I to period II. For both periods, multibacillary leprosy was the most
      frequent clinical form of the disease (+/-68%), and the main infection risk
      factor identified was household contact. Leprosy is predominantly manifested in
      adults, but an increase in the number of very old and very young patients was
      observed in period II. The MDT program has been effective both in combating
      leprosy and in promoting awareness of the disease.

PMID- 10883035
TI  - [The trajectory towards alternative medicines: an analysis of health
      professionals' social representations].
AB  - This article focuses on social representations of alternative medicines by a
      group of professors from the School of Medicine and health professionals from the
      public health system in the city of Campinas, Sao Paulo, basically physicians and
      nurses. The article also emphasizes personal trajectories by which these health
      professionals opted for a dissident theoretical and practical perspective vis-a
      vis the hegemonic positivist scientific medical paradigm. The research methods
      were mainly ethnographic, from a phenomenological perspective. The article
      concludes by sustaining (in theoretical terms) the importance of these dissident
      perspectives for scientific development.

PMID- 10883036
TI  - [Women and contraception: knowledge and use of contraceptive methods].
AB  - This article analyzes knowledge and use of contraceptive methods in women ages 10
      to 49 years residing in the southern region of the city of Sao Paulo in 1992. A
      total of 1,157 childbearing-age women were studied, focusing on variables that
      might define them as to: knowledge in the use of contraceptive methods and
      reasons for choosing a given method. We observed that 86% of the women referred
      knowledge of some contraceptive method, while the most common was the pill
      (95.3%), followed by condoms (92.6%). Meanwhile, 14% of the interviewees denied
      knowledge of any contraceptive method. Of the sexually active women (66.4%),
      34.9% reported never having used contraceptive methods. Of those who had, 35.3%
      used the pill, while 42.9% had resorted to sterilization. Only 5.2% used condoms.
      Despite the high level of knowledge concerning contraceptive methods, especially
      oral contraceptives and condoms, we observed limited use of same as compared to
      the high sterilization rate around the age of 27, thus leaving contraception
      limited to the pill and female sterilization.

PMID- 10883037
TI  - [Ideology and gender relations: a reception study about AIDS prevention
      campaigns].
AB  - This article refers to a reception research of seven television prevention
      campaigns, done in South Brazil - Porto Alegre, Rio Grande do Sul, with 38 women,
      ages 18-51 years old, from low-income class. The sample was divided in two
      groups: women that don't participate in groups that fight against AIDS/HIV and
      women that participates in groups that fight against AIDS/HIV. Based in a
      qualitative framework, the Depth Hermeneutic and the Feminist Theory were
      employed in order to study the ideology and gender relations underneath the
      campaigns' messages. The results indicate that for both groups of women
      television is an important source of AIDS related information, although they
      believe the campaigns do not stimulate the use of condom. While the first group
      of women agrees and identifies themselves with the majority of messages and
      images within the campaigns, the second group perceives that behind the messages
      the voice of the ideology operates, throughout a variety of strategies, to create
      and to establish relations of domination.

PMID- 10883038
TI  - [Professional medical identities in contention: The National Practitioners'
      Congress, Brazil (1922)].
AB  - The object of this paper is the debate among the Brazilian medical elite during
      the National Practitioners' Congress (Congresso Nacional dos Praticos - 1922).
      The article begins by analyzing a specific moment in the medical profession's
      history in early 20th-century Brazil, specifically Rio de Janeiro's 1922 National
      Practitioners' Congress. The author presents three profiles of medical practice
      observed in that context: generalists, specialists, and hygienists. He further
      analyzes their characteristics, similarities, and differences, as well as the
      strategies for professional affirmation adopted by physicians with these
      profiles. The article addresses the following issues: What were the relationships
      between the specialization process, forms of remuneration, and the construction
      of new professional identities? What identities did medical doctors create for
      themselves? What were the rivalries between these different professional
      identities? How did they portray outside competitors, such as the so-called
      traditional healers? Finally, the author presents several methodological
      suggestions that may contribute to historical research on the medical profession.

PMID- 10883039
TI  - [Obstetric care during childbirth in Rio de Janeiro: hospital practices and user
      access].
AB  - The purpose of this paper is to identify and describe Rio de Janeiro maternity
      hospital profiles and the route between the mother's place of residence and the
      hospital. Data sources were: the State Live Birth Information System (1995) and
      the National Survey on Medical Care (1992). Two groups of maternity hospitals
      were identified using multivariate cluster analysis. Group A had an extremely
      high cesarean rate (81%), with mothers and neonates presenting good health
      conditions. Cesarean rates were lower in Group B, although still high (32%), and
      other variables reflected worse neonatal conditions. Cesarean rate was the
      indicator which best discriminated between the groups, followed by proportion of
      adolescent mothers and mothers with a high school education. The uneven spatial
      distribution of maternity hospitals, which were concentrated in the richest area
      of the city, was a factor in the long routes used by women to reach medical care
      for childbirth.

PMID- 10883040
TI  - [(Mis)information on drugs: the double standard practiced by pharmaceutical
      companies].
AB  - Different factors have been identified as influencing drug prescribers. Some
      studies emphasize the role played by sources of information available to
      physicians. Reports have been published on the influence of marketing strategies
      on these health professionals. Such strategies include advertisements in medical
      journals, sales representatives, free samples, leaflets, distribution of gifts
      and prizes, etc. The research reported here aimed to identify information
      provided by a commonly used Brazilian prescription handbook, the Dicionario de
      Especialidades Farmaceuticas (DEF), in relation to the 44 most frequently sold
      pharmaceutical products in Brazil, using as parameters the WHO guidelines for
      information to be included in informative materials offered to physicians. The
      information was then compared to that included in the PDR (Physicians' Desk
      Reference) and USP-DI (Drug Information for the Health Care Professional) used by
      prescribers in the United States. The results showed lack of data in the
      Brazilian publication (contraindications, side effects, drug interaction),
      suggesting lack of reliability in prescription quality and thus in the ultimate
      utilization of drugs.

PMID- 10883041
TI  - [Neonatal mortality trends in Sao Luis, Maranhao, Brazil, from 1979 to 1996].
AB  - This study examined neonatal mortality trends in Sao Luis in the last 18 years.
      The early and late components were assessed and causes were classified according
      to SEADE Foundation criteria based on reducibility of deaths and timing of
      prevention (during prenatal care, childbirth, or neonatal care). Data were
      derived from official live birth and death records. We detected an unexpected
      increase in the neonatal mortality rate, due primarily to a steep rise in early
      neonatal deaths. Causes reducible by early diagnosis and treatment (other
      specific infections and other neonatal respiratory causes) and those partially
      reducible by adequate monitoring of pregnancy (preterm births, low birth weight,
      and respiratory distress syndrome) showed the largest increase. Conversely, the
      post-neonatal mortality rate fell. The infant mortality rate remained the same,
      reflecting these antagonistic trends. The important rise in the neonatal
      mortality rate from 1995 onwards suggests a deterioration in the quality of
      obstetric and neonatal services. The high cesarean rate and overcrowded neonatal
      services (i.e., unable to cope with increasing demands foe specialized neonatal
      care) indicate the urgent need for restructuring the mother and child health care
      system.

PMID- 10883042
TI  - [Reclink: an application for database linkage implementing the probabilistic
      record linkage method].
AB  - This paper presents a system for database linkage based on the probabilistic
      record linkage technique, developed in the C++ language with the Borland C++
      Builder version 3.0 programming environment. The system was tested in the linkage
      of data sources of different sizes, evaluated both in terms of processing time
      and sensitivity for identifying true record pairs. Significantly less time was
      spent in record processing when the program was used, as compared to manual
      processing, especially in situations where larger databases were used. Manual and
      automatic processes had equivalent sensitivities in situations where we used
      databases with fewer records. However, as the number of records grew we noticed a
      clear reduction in the sensitivity of the manual process, but not in the
      automatic one. Although in its initial stage of development, the system performed
      well in terms of both processing speed and sensitivity. Although overall
      performance of algorithms was satisfactory, we intend to evaluate other routines
      in the attempt to improve the system's performance.

PMID- 10883043
TI  - [Information level about drugs prescribed to ambulatory patients in a university
      hospital].
AB  - Lack of information on medication is one of the main reasons why some 30-50% of
      patients fail to take their medicines as prescribed. To assess patient knowledge
      about prescribed drugs, outpatients from an internal medicine clinic in a
      teaching hospital were interviewed after medical consultation. Patients were
      asked to identify the name, indication, dosage, administration schedule, duration
      of treatment, side effects, and precautions. Patients' answers were compared to
      medical prescription or patients' medical records. Two hundred and sixty-four
      patients were interviewed, of whom 34% displayed satisfactory knowledge. In 31%
      of cases the drug name stated was incorrect, while in 19% the reported indication
      differed from that on the medical records. Dosage and administration schedules
      stated by patients disagreed with physician's instructions in 19% and 31% of
      cases, respectively. The results suggest that the majority of outpatients have
      sufficient knowledge for the safe use of prescribed drugs, under an ideal
      outpatient setting.

PMID- 10883044
TI  - [Breastfeeding knowledge among post-partum women enrolled in a prenatal care
      program].
AB  - The purpose of this study was to evaluate knowledge of breastfeeding issues among
      post-partum women who had participated in a prenatal program at the Rio de
      Janeiro Federal University (UFRJ) Maternity Teaching Hospital. The sample totaled
      135 post-partum women who answered a structured questionnaire with objective
      questions about practical and theoretical aspects of breastfeeding. The women had
      begun prenatal care at the 16th week of gestation on average, with an average of
      8 medical consultations. Some 53.3% stated having received information about
      breastfeeding during prenatal care, and 22.2% stated that the information they
      remembered the best was that they should breastfeed for the first 6 months.
      Regarding the best moment for the first feeding, 50.4% identified it as
      immediately after delivery. Some 47.4% said breastfeeding protects the child from
      diseases. Thus, although the mothers demonstrated basic knowledge about
      breastfeeding, issues like the best moment for the first feeding, the importance
      of colostrum, and nutritional aspects for nursing mothers require further
      clarification during prenatal care and the immediate post-partum period.

PMID- 10883045
TI  - [Voronoi s Diagram for defining catchment areas for public hospitals in the
      Municipality of Rio de Janeiro].
AB  - One of the most important pieces of information for health resources planning is
      the definition of catchment areas for health units. Voronoi Diagrams are a
      potential technique for this purpose. They are polygons with the property whereby
      adjacent polygons have their borders located within the same distance of the
      respective generator points. One possible adjustment to the catchment areas thus
      defined is the use of weighted Voronoi Diagrams, which result in an improved
      representation of a health unit's actual capacity. In this study, the 21 public
      general hospitals in the city of Rio de Janeiro, Brazil, were used as generator
      points for Voronoi Diagrams. Non-weighted Voronoi Diagrams were initially
      implemented and then used as the basis for obtaining weighted Voronoi Diagrams,
      using as weights the annual admission rates estimated for each unit. In the
      classic Voronoi Diagram case, some catchment areas had similar sizes, although
      their respective health units had different characteristics. In the weighted case
      the areas were modified in a way that appeared closer to the actual functioning
      of the units. The method appeared simple to implement, used easy-to-access data,
      and did not rely on geopolitical considerations such as existing administrative
      areas. It thus provided a more realistic picture of a unit's capacity to support
      basic health programs.

PMID- 10883046
TI  - [Risk factors for neonatal and post-neonatal mortality in the Central-West region
      of Brazil: linkage between live birth and infant death data banks].
AB  - This article focused on risk factors for neonatal and post-neonatal mortality by
      linking live births and infant death records. The study was conducted in the
      municipality of Goiania, in the Central-West region of Brazil. A total of 20,981
      live births and 342 infant deaths constitute the retrospective cohort. Neonatal
      and post-neonatal mortality risks were estimated in this cohort study of live
      births by logistic regression. In the neonatal period, the highest ORs were for
      delivery in public hospitals (OR = 2.28; 95% CI 1.57-3.32), pre-term neonates (OR
      = 8.94; 95% CI 5.85-13.67), and low birth weight (OR = 8.92; 95% CI 5.77-13.79).
      Cesarean delivery appeared as a protective factor (OR = 0.58; 95% CI 0.43-0.78).
      For post-neonatal mortality, the highest ORs were for illiterate mothers (OR =
      6.25; 95% CI 1.25-31.27), low birth weight (OR = 3.12; 95% CI 1.67-5.84), and
      delivery in public hospitals (OR = 2.65; 95% CI 1. 13-6.23). The linkage
      identified socioeconomic variables that were more important risk factors for post
      neonatal than neonatal mortality.

PMID- 10883047
TI  - [Essay on the epistemological relationship between probability and scientific
      method].
AB  - In the XIX century, regularities in statistics of events were perceived in
      Medicine and Human Sciences. These regularities raised the possibility of
      forecasting what considered to be impredictable, and so, probabilistics laws
      became an alternative to the strictly-causal laws. This work presents a brief
      historical review of probability calculus and its applications. Some
      philosophical thoughs, regarding the use of probabilistics models and decision
      analysis in Medicine, are also discussed.

PMID- 10883048
TI  - [Social representations and history: theoretical and methodological principles
      for public health].
AB  - This article discusses the concept of social representations on health and
      illness from a social/historical point of view, to provide the means for
      developing research in the public health care domain. To situate this discussion,
      the analysis was based on field research health issues, attempting to demarcate a
      theoretical frame of reference with the help of reference literature in sociology
      and cultural history, while also contemplating cultural anthropological studies
      conducted in the medical field.

PMID- 10883049
TI  - [Health care models: organization of Reference Teams in the health basic network
      of Secretaria Municipal de Saude of Betim, Minas Gerais State, Brazil].
AB  - This article describes and analyzes a new basic health care system approach
      termed Reference Teams, or health unit teams accountable for a reference
      population, organized in Betim, Minas Gerais. Empirical data and other forms of
      evidence were collected by the authors with the purpose of describing the
      project's history. Based on this experience and other studies on the subject,
      some theoretical reflections shaping models for health care reform were
      formulated.

PMID- 10883050
TI  - A Bayesian approach to estimate the prevalence of low height-for-age from the
      prevalence of low weight-for-age.
AB  - Victora et al. (1998) proposed the use of low weight-for-age prevalence to
      estimate the prevalence of height-for-age deficit in Brazilian children. This
      procedure was justified by the need to simplify methods used in the context of
      community health programs. From the same perspective, the present article
      broadens this proposal by using a Bayesian approach (based on Markov Chain Monte
      Carlo (MCMC) methods) to deal with the imprecision resulting from Victora et
      al.'s model. In order to avoid invalid estimated prevalence values which can
      occur with the original linear model, truncation or a logit transformation of the
      prevalences are suggested. The Bayesian approach is illustrated using a community
      study as an example. Imprecision arising from methodological complexities in the
      community study design, such as multi-stage sampling and clustering, is easily
      handled within the Bayesian framework by introducing a hierarchical or multilevel
      model structure. Since growth deficit was also evaluated in the community study,
      the article may also serve to validate the procedure proposed by Victora et al.

PMID- 10883051
TI  - [The epidemiology of the nutritional deficiencies in the Northeast: the
      contribution of Malaquias Batista Filho to the institutionalization of nutrition
      in Public Health in Brazil. Interview by Francisco de Assis Guedes de
      Vasconcelos].

PMID- 10883052
TI  - [Death of elderly patients in the Santa Genoveva Clinic in Rio de Janeiro: excess
      mortality that the public health system could have prevented].
AB  - From January to May 1996, 156 inpatients died in a clinic for elderly people in
      Rio de Janeiro, Brazil. The highest mortality rate was observed in May: 143/1,000
      inpatients. As a result, the clinic was closed by the Ministry of Health. This
      study investigated whether the excessive number of deaths observed in the clinic
      in early 1996 was unexpected or reflected prevailing conditions. The
      investigation used the Public Health System database (SIH-SUS). The study period
      was 01/1993 to 05/1996. The investigation was based on: 1) a time-series analysis
      of the number of deaths and crude mortality rates and 2) comparison of the
      mortality rates observed in that clinic with those calculated for 15 area
      hospitals, defined as the reference rates. Risk of death in the clinic was higher
      than expected in 28 of the 41 months considered in the study. Highest risks were
      observed in January 1993 (RRcrude = 2.23; 95% CI 1.56-3. 14) and May 1996
      (RRadjusted = 2.73; 95% CI 1.88-3.95). The high mortality rates observed in the
      clinic in 1996 were already present in 1993. Thus, adequate use of the SIH-SUS
      could have anticipated and avoided the excess mortality identified in early 1996.

PMID- 10883053
TI  - [Perceptions of the effects of shift work on health and social life of nursing
      employees in a university hospital of Sao Paulo State].
AB  - There is a relationship between shift work and the beginning of organized life.
      Health services require shift work to keep activities running twenty-four hours a
      day. This study thus aimed to identify nursing staff shift work systems in a
      university hospital, evaluate health workers' perceptions of the possible effects
      of shift work on their health and social life, and assess workers' participation
      in preparing nursing schedules. In terms of materials and methods, this was an
      exploratory and descriptive study with a sample of 348 nursing staff members,
      using an appropriate questionnaire. Most were married women under 40 with at
      least one child, working on rotating shifts with more than fifteen-days frequency
      of rotation, and with neurological, psychological, gastrointestinal, and
      cardiovascular health complaints. They also reported relational problems on the
      job. Most of the nursing staff played a minor role in preparing nursing
      schedules.

PMID- 10883054
TI  - [Social network and social support among poor elderly ill in Guadalajara,
      Mexico].
AB  - This paper examines social networks and social support among poor elderly ill in
      Guadalajara, Mexico. We interviewed 40 hospitalized elderly patients. The mean
      size of social networks was 7.5, basically involving women, multiple generations,
      and members of the extended family. Emotional support was more frequent than
      other types of social support. Elderly women had larger social networks and
      received more social support than men. Married elderly also had larger social
      networks and more social support than single patients. There were no differences
      between age and living arrangements with social networks and social support.
      Future studies are needed on the social and cultural environment of social
      support for the elderly.

PMID- 10883055
TI  - [A method for teaching mathematics].
AB  - This paper reports on an experience in teaching mathematics in a graduate course
      in public health, intermingled with reflections and concepts. Students enrolled
      in such courses generally feel uneasy about learning mathematics. Without
      underrating the usual obstacles and even affinities in developing abstractions,
      the results suggest that a major portion of the difficulties derives not from
      mathematics itself, but from an oppressive experience in the past. Difficulties
      also relate to the construction of space in the classroom. Such a perspective
      involves understanding experiments and life experiences in which the subjects are
      involved. In short, the work focuses on how to transmit mathematics in the
      development of a pedagogical approach.

PMID- 10883056
TI  - [Canine leishmaniasis: a serological survey of 310 dogs in Itaipu, Rio de
      Janeiro, Brazil].

PMID- 10883057
TI  - Discordant effect of aspirin and indomethacin on intestinal tumor burden in
      Apc(Min/+)mice.
AB  - Epidemiologic and animal studies indicate that sustained use of non-steroidal
      anti-inflammatory drugs (NSAIDs) have a chemopreventive effect against the
      incidence of colorectal neoplasia and subsequent mortality. We previously
      demonstrated that sulindac significantly reduces intestinal tumor load in
      Apc(Min/+)mice and the tumor regression was not necessarily correlated with
      prostaglandin biosynthesis. In the present study, we further investigate the
      relationship of NSAID treatment and tumorigenesis in the Apc(Min/+)mouse model.
      We demonstrate that indomethacin (9 ppm) is a very potent chemopreventive agent,
      reducing tumor load by 85% and significantly inhibiting basal and ex vivo
      prostaglandin formation (P< 0.006 and P< 0.0001, respectively). Aspirin (400 ppm)
      has a similar impact on reducing prostaglandin levels, but in contrast to
      indomethacin, is uneffective in reducing the tumor load. The data indicate a
      discordance between the impact of different NSAIDs on tumorigenesis in
      Apc(Min/+)mice.

PMID- 10883059
TI  - Modifications in the TXA(2) and PGI(2) plasma levels and some other biochemical
      parameters during the initiation and development of non-insulin-dependent
      diabetes mellitus (NIDDM) syndrome in the rabbit.
AB  - Having developed a non-insulin-dependent diabetes mellitus (NIDDM) syndrome model
      in the rabbit using Wirsung duct ligation, it appeared interesting to use it to
      study the relationship between glycemia and the plasma levels of TXA(2)and
      PGI(2), and of some other biochemical parameters such as cholesterol,
      triglycerides, alkaline phosphatase and transaminases. A comparative study was
      carried out in the sham-operated rabbits (controls, C) and those having their
      pancreatic duct ligatured (NIDDM, D) at 15, 30, 40, 50 and 60 days post-ligation.
      On the 40th days, whereas in the controls, glycemia was 1.17 +/- 0.04 g.l(-1), it
      reached a maximum of 4.62 +/- 0.76 g.l(-1)(25.40 mM) in the NIDDMs. No
      significant modification was observed either in cholesterolemia or in
      triglyceridemia in either group. The GOT and GPT were highly increased, from
      11.50 +/- 4.00 IU. l(-1)and 27.00 +/- 1.50 IU.l(-1)(C) to 37.50 +/- 5.64 IU.l(
      1)(P<0. 001) and 58.50 +/- 7.50 IU.l(-1)(D) (P<0.001) in the NIDDM group,
      suggesting that hyperglycemia occurred simultaneously with the degeneration of
      the pancreatic tissue. In parallel, in D rabbits, the plasma levels of TXB(2)and
      6 keto PGF(1alpha)were augmented to 68.22 +/- 6.20 pg.ml(-1)versus 22.49 +/- 5.74
      pg.ml(-1)(C) (P<0.001), and 127.11 +/- 14.39 pg.ml(-1)versus 48.65 +/- 4.51
      pg.ml(-1)(C) (P<0. 001) respectively. Statistical studies showed a significant
      correlation (P<0.05 and <0.02) between glycemia and the biosynthesis of
      eicosanoids under study. Moreover, 25 mM was found to be the threshold level of
      glucose excess essential to increase the TXA(2)and PGI(2)biosynthesis
      significantly. This supports the results obtained by other authors studying the
      action of glucose on phospholipase activity and consequent eicosanoid production.

PMID- 10883058
TI  - Mechanism for antiplatelet effect of onion: AA release inhibition, thromboxane
      A(2)synthase inhibition and TXA(2)/PGH(2)receptor blockade.
AB  - Antiplatelet actions of aqueous extract of onion were investigated in rat and
      human platelet. IC(50)values of onion extract for collagen-, thrombin-,
      arachidonic acid (AA)-induced aggregations and collagen-induced thromboxane
      A(2)(TXA(2)) formation were 0.17 +/- 0. 01, 0.23 + 0.03, 0.34 +/- 0.02 and 0.12
      +/- 0.01 g/ml, respectively. [(3)H]-AA release induced by collagen (10 microg/ml)
      in rat platelet was decreased by onion compared to control (22.1 +/- 2.13 and 5.2
      +/- 0.82% of total [(3)H]-AA incorporated, respectively). In fura-2 loaded
      platelets, the elevation of intracellular Ca(2+)concentration stimulated by
      collagen was inhibited by onion. Onion had no cytotoxic effect in platelet. Onion
      significantly inhibited TXA(2)synthase activity without influence on COX
      activity. Platelet aggregation induced by U46619, a stable TXA(2)mimetic, was
      inhibited by onion, indicating its antagonism for TXA(2)/PGH(2)receptor. These
      results suggest that the mechanism for antiplatelet effect of onion may, at least
      partly, involve AA release diminution, TXA(2)synthase inhibition and
      TXA(2)/PGH(2)receptor blockade.

PMID- 10883060
TI  - The roles of platelet function, thromboxane, blood lipids and nitric oxide in
      hypertension of children and adolescents.
AB  - The roles of platelet function, plasma lipids and nitric oxide (NO) were studied
      in adolescent patients with essential hypertension (JEHT group), with chronic
      renal failure (CRF) associated with hypertension (CRFH group), and CRF patients
      with normal blood pressure (CRF group), as compared with normal controls (cont.
      group). Platelet aggregation and the thromboxane B(2)(TxB(2)) level were
      significantly higher in the JEHT and CRFH groups as compared with the cont.
      group, whereas they were significantly lower in the CRF group. On the other hand,
      the platelet cAMP level was significantly lower in the JEHT and CRFH groups than
      in the cont. group. The plasma NO level was significantly higher only in the JEHT
      as compared with the cont. group (120 +/- 39 and 89 +/- 21 microM, respectively).
      The plasma total cholesterol, triglyceride and LDL cholesterol concentrations
      were normal in the JEHT group, but high in the CRF and CRFH group, the HDL
      cholesterol level was lower in the CRF and CRFH groups as compared with the cont.
      and JEHT groups. There was a positive correlation between the platelet
      aggregation and the TxB(2)level and between the BP and the platelet aggregation.
      In conclusion, hyperlipidaemia is commonly present in uraemia with haemodialysis,
      but is not specific for hypertension in children, while an increased platelet
      function is frequently associated with hypertension. The increased NO level might
      play a compensatory role in JEHT.

PMID- 10883061
TI  - Metabolism of n -9, n -6 and n -3 fatty acids in hepatoma Morris 7777 cells.
      Preferential accumulation of linoleic acid in cardiolipin.
AB  - The objective of this study was to investigate, using a pulse-chase technique,
      the different incorporation of (1-(14)C) n -9, n -6 and n 3 fatty acids into
      hepatoma lipids and their secretion to the culture medium. Docosahexaenoic acid
      (DHA) accumulated preferentially into the triacylglycerol while arachidonic acid
      (AA) did into the phospholipid fraction. DHA was poorly secreted to the culture
      medium whereas AA was secreted to a large extent. The fatty acids were initially
      esterified mainly into phosphatidylcholine and phosphatidylethanolamine. During
      the 24 h chase, a general shift from phosphatidylcholine to
      phosphatidylethanolamine was observed. Linoleic acid was esterified in
      cardiolipin to a much greater extent than any other fatty acid and it was not
      converted to more polyunsaturated fatty acids. The supplementation of the culture
      medium with polyunsaturated fatty acids had no inhibitory effect on the growth of
      the hepatoma cells, in marked contrast to observations made in other tumoral
      cells. The reasons for the resistance of the hepatoma cells to polyunsaturated
      fatty acid toxicity, including the possible antioxidant effect of linoleic acid
      accumulation in cardiolipin, are also discussed.

PMID- 10883062
TI  - Comparison of maritime pine oil and fish oil effects on plasma lipoproteins in
      apolipoprotein E-deficient mice.
AB  - The goal of this study was to compare the lipid lowering properties of maritime
      pine and fish oils in apolipoprotein E-deficient (KOE) mice, an animal model of
      hyperlipidemia. KOE mice were supplemented with either lard, fish or maritime
      pine oil (10% w/w) for one month. Compared to lard, fish and maritime pine oils
      decreased cholesterol (-31% and -52% respectively) and phospholipid (-41 and 
      52%) levels and increased triglyceride (+182% and +123%) levels. These lipid
      changes resulted in an enrichment in triglycerides and a depletion in cholesterol
      of VLDL+IDL plasma fraction as compared to lard-fed mice. These findings suggest
      that VLDL-triglyceride lipolysis is impaired in KOE mice fed fish or maritime
      pine oil.

PMID- 10883063
TI  - Effects of a novel non-carboxylic thromboxane A2 receptor antagonist (BM-531)
      derived from torasemide on platelet function.
AB  - In this study we examined the thromboxane A(2)(TXA(2)) receptor antagonist
      property of BM-531 (N-tert -butyl- N'-[(2-cyclohexylamino-5
      nitrobenzene)sulfonyl]urea), a torasemide derivative, on platelet function. The
      drug affinity for human washed platelet TXA(2)receptors labelled with [(3)H]SQ
      29,548 has been determined (IC50: 0.0078 microM) and demonstrated to be higher
      than sulotroban (IC50: 0.93 microM) and SQ-29,548 (IC50: 0.021 microM). The
      antiaggregatory potency has been confirmed since we demonstrated that BM-531
      prevented platelet aggregation in human citrated platelet-rich plasma induced by
      arachidonic acid (600 microM) (ED100: 0.125 microM), U-46619, a stable
      TXA(2)agonist (1 microM) (ED50: 0.482 microM) and collagen (1 microg mL(-1)) (%
      of inhibition: 42.9% at 10 microM) and inhibited the second wave of ADP (2
      microM). Moreover, when BM-531 was incubated in whole blood from healthy donors,
      the closure time measured by the recently developed platelet function analyser
      (PFA-100(trade mark)) was significantly prolonged. These results suggest that BM
      531 can be regarded as a novel non-carboxylic TXA(2)antagonist with a powerful
      antiplatelet potency.

PMID- 10883064
TI  - Relationship between the ability to support differentiation of osteoclast-like
      cells and adipogenesis in murine stromal cells derived from bone marrow.
AB  - In vitro osteoclast differentiation is supported by stromal cells. In order to
      isolate a stromal cell line that can support osteoclast differentiation, 22 cell
      lines were cloned from mouse bone marrow. One of these clones, TMS-14, is a line
      of preadipocytes that supports osteoclast-like cell formation without any bone
      resorbing factors; and another, TMS-12, is a line of preosteoblasts that supports
      osteoclast-like cell formation with bone resorbing factors such as prostaglandin
      E(2)(PGE(2)). The difference of these two lines for osteoclast formation was not
      related with their abilities of PGE(2)production, but with the expression of
      osteoclast differentiation factor (ODF, also called OPGL, RANKL, and TRANCE),
      which detected with RT-PCR, in both cell lines. In TMS-14 cells, ODF mRNA was
      detected with or without PGE(2). In TMS-12 cells, ODF expression was detected in
      the PGE(2)-treated cells alone. When TMS-14 cells were induced to undergo
      adipogenic differentiation in response to treatment with thiazolidinedione, a
      ligand and activator of peroxisome proliferator-activated receptor gamma
      (PPARgamma), the ability of TMS-14 cells to support osteoclast-like cell
      formation was prevented in the presence or absence of 1,25(OH)(2)D(3). The gene
      expression of ODF in TMS-14 cells was also inhibited by treatment with
      thiazolidinedione. These results suggest that adipogenesis in bone marrow cells
      is related to the ability to support osteoclast differentiation. This is the
      first report of a cloned stromal cell line that can support osteoclastogenesis
      without the treatment with any osteotropic factors. Furthermore, this murine
      clonal preadipose cell line may be useful for studying senescence-dependent
      osteoporosis.

PMID- 10883065
TI  - [Transarterial oil chemoembolization for hepatocellular carcinoma, in 100 cases].
AB  - Hepatocellular carcinoma (HCC) is a common malignancy with a grave prognosis.
      Most patients have both the malignant tumor as well as hepatic cirrhosis. Liver
      transplantation or hepatectomy are considered the only curative procedures, but
      can be applied in fewer than 10% of patients. In recent decades the most common
      treatments of HCC are transarterial chemoembolization with oil (TOCE) and
      percutaneous ethanol injection (PEI). We summarize our retrospective study of 100
      patients (mean age 64 +/- 3) treated by TOCE. In 271 procedures between 1989
      1998, in 16 patients hepatectomy was combined with TOCE and in 8 PEI was combined
      with TOCE, while the rest were treated by TOCE alone. Tumor mass was reduced in
      36% of those treated by TOCE (tumor volume reduced 24-75%). Alpha-feto protein
      (AFP) was reduced 25-90% in 20/32 of those with elevated AFP levels. Median
      survival for the 100 in the entire group was 19 months (10.9 months in those with
      conservative treatment). Median survival in the 57 in Okuda stage 1 and the 43 in
      stages 2 or 3 was 30.1 months and 10.9 months, respectively (p < 0.0001). Of the
      57 in stage 1, 16 underwent hepatectomy in addition to TOCE and 41 were treated
      only by TOCE (median survival 15 and 26 months, respectively, p not significant).
      Comparing Okuda 1 patients treated by TOCE only with the natural history of the
      disease and historical controls (Okuda 1 patients treated conservatively in 1984)
      median survival was 26 and 10 months respectively (p < 0.001). The side effects
      of TOCE were relatively mild. There was 1 fatality (3 days after treatment), and
      quality of life was maintained. Despite progress in the treatment of HCC by TOCE,
      PEI, and liver transplantation, long-term survival has remained unsatisfactory.

PMID- 10883066
TI  - [Preliminary experiences with endoscopic parathyroidectomy].
AB  - Since the advent of extraperitoneal approaches for laparoscopic surgery, the
      creation of extraperitoneal virtual spaces has spread rapidly. We describe our
      preliminary experience with selective neck exploration and endoscopic
      parathyroidectomy in 4 women, aged 57-74, with primary hyperparathyroidism.
      Preoperative localization of parathyroid adenoma was assessed by technetium
      sestamibi scanning and cervical ultrasonography. A cervical work space was
      created by the introduction of a trocar with an inflatable balloon-tip and
      maintained with low-pressure CO2 insufflation. All procedures were completed
      endoscopically. There were no intraoperative complications. Mean operative time
      was 40 minutes and cosmetic results were very satisfactory. We found endoscopic
      parathyroidectomy a feasible and safe option and particularly appropriate for the
      surgical treatment of primary hyperparathyroidism. Further refinements in
      technique will enhance its practicability in exploring the mediastinum for
      ectopic parathyroid glands and in those with secondary hyperparathyroidism.

PMID- 10883067
TI  - [Brief preoperative radiotherapy reduces local recurrences and improves survival
      in rectal cancer].
AB  - Locoregional recurrence of rectal cancer ranges between 20%-50% following
      apparently radical surgery. Radiation has the potential of reducing this high
      rate of recurrence and residual disease. A retrospective analysis of 78 patients
      with locally advanced, biopsy proven, adenocarcinoma of the rectum treated
      between 1980-1987 was conducted. 28 (36%) were treated by surgery alone
      (surgery); 29 (37%) by surgery and postoperative radiotherapy (post-op); and 21
      (27%) by surgery and preoperative radiotherapy (pre-op). 41 were females and 37
      males. The median age was 62 years (range 25-90). All tumors were resectable. 42
      patients (54%) underwent abdomino-perineal resection and 36 (46%) anterior
      resection [8 patients Dukes B1 (10%); 37 B2 (47%); 2 C1 (3%); 31 C2 (40%)]. Local
      recurrences were verified by transanal or ultrasound guided needle biopsy. The 5
      year actuarial survival rates by the Kaplan-Meier method for 75 evaluated
      patients was 55%. Overall 5-year actuarial survival was significantly higher (p =
      0.001) in pre-op radiotherapy (95%) compared to surgery alone (45%), or surgery
      with postoperative radiotherapy (32%). The data were significant (p = 0.006) for
      patients with stage B tumors, but not stage C. This trend of improved survival
      held also at 8-year follow-up (80% pre-op; 32% post-op; 27% surgery). The 5-year
      actuarial local control was significantly better (p = 0.03) for the pre-op
      irradiated patients (22%), compared with surgery only (56%) and post-op
      radiotherapy (38%). Local control was better (p = 0.02) for Dukes B tumors in the
      preoperative group, but not Dukes C tumors. Actuarial 5-year survival of those
      without distant metastases was 87% for pre-op patients, 62% for surgery alone and
      48% for post-op radiotherapy. As all patients were clinically classified as
      advanced rectal tumors, tumor downstaging by preoperative radiotherapy seems to
      be paramount for local control. Improved local control translates into a
      significant advantage in overall actuarial survival.

PMID- 10883068
TI  - [Recurrent anaphylactic reactions during hospitalization--an unusual etiology].
AB  - The prevalence of hypersensitivity and untoward reactions to natural rubber latex
      (NRL) products is increasing, particularly among specific risk groups. A young
      man aged 23 years who experienced several episodes of allergic reactions, 2 of
      which included anaphylactic shock during hospital admission, is presented. These
      episodes were initially attributed to intravenous medication, but were most
      probably caused by inadvertent exposure to latex. Medical facilities may contain
      large amounts of latex, and therefore present a hazardous environment for
      sensitive people. Increasing awareness of latex sensitivity among patients-at
      risk and medical personnel, and implementing simple prophylactic measures, may
      reduce morbidity and mortality. We propose simple and practical guidelines for
      diagnosis and treatment.

PMID- 10883070
TI  - [Solid and papillary pancreatic neoplasm].
AB  - Solid and papillary neoplasm of the pancreas is an interesting and rare malignant
      tumor. It occurs most commonly in young women. It was first described in 1959 and
      since then has been referred to by different names, including solid and cystic
      tumor, solid and cystic epithelial neoplasms, and others. Its malignant potential
      is low and metastasis is very rare. Treatment includes partial pancreatectomy
      with full resection of the tumor. The prognosis is generally very good. We
      present 3 women (aged 17, 19, 39) diagnosed and treated for solid and papillary
      neoplasm of the pancreas. The unique clinical, histological, and epidemiological
      characteristics of this tumor are detailed.

PMID- 10883069
TI  - [Gyrate atrophy of choroid and retina, and hyperornithinemia].
AB  - Gyrate atrophy of the choroid and retina is a rare degenerative disease,
      characterized biochemically by a marked increase in blood ornithine levels, due
      to deficiency of ornithine S-amino transferase. 4 men aged 35, 36, 48 and 62
      years are described with different stages of myopia, night blindness and loss of
      peripheral vision, which progressed to tunnel vision and partial blindness. Onset
      of the disease was at ages 3, 10 and 15 years, respectively, while in the 4th
      patient there was delayed expression starting at about age 50. Most had posterior
      subcapsular cataracts, and the ocular fundus exhibited demarcated circular areas
      of chorioretinal degeneration. So far the only patients described in Israel have
      been of Iraqui origin. Our fourth patient originated from Istanbul, and he may
      represent a hitherto undescribed variant with a much delayed expression of the
      disease.

PMID- 10883071
TI  - [Progressive ptosis in children as a presenting sign of Kearns-Sayre syndrome].
AB  - Mitochondrial encephalopathies represent a heterogeneous group of various
      neurological syndromes caused by defects in mitochondrial metabolism. All
      clinical syndromes can be subdivided by type of biochemical defect into 3
      subgroups: defective oxidation, defects in pyruvate metabolism and various
      defects in the respiratory chain. We present a 12-year-old girl admitted for
      evaluation of progressive ptosis over a period of 3 years, diagnosed as having
      the rare mitochondrial encephalopathy, Kearns-Sayre syndrome.

PMID- 10883072
TI  - [Cost-effectiveness of imaging procedures in knee injuries].
AB  - It is clear to experts in the health care industry that with regard to medical
      decision-making, considering costs of medical devices is not a good index, but it
      is highly important to include medical aspects. This approach guarantees an
      advance and an appropriate method. We present a cost-effectiveness analysis to
      target the optimal strategy of how to use medical diagnostic devices in cases of
      knee injuries. Today, one of the more common medical emergency referrals seen
      worldwide is in the area of orthopedics, knee injuries in particular. They can
      harm soft tissue, bone tissue, or both simultaneously. The diagnosis of soft
      tissue injury is difficult at best. Among the devices helping the clinician make
      an accurate diagnosis are MRI and ultrasound (US). We conclude that US is
      superior to MRI in this condition. This is especially true when the orthopedic
      examination leads to the suggestion of arthroscopy. The results were not
      modified, and a sensitive study of the parameters that influence the decision
      making process was undertaken. Decision-makers should not consider medical
      outcome alone, but should take into account the costs. A clinical study should
      validate the assumption on which this study was based.

PMID- 10883073
TI  - [Smallpox--has the danger passed? The history of the disease and the war against
      it].

PMID- 10883074
TI  - ["And nevertheless...autoimmunity"--celiac disease and the antibodies to tissue
      transglutaminase].

PMID- 10883075
TI  - [Fixed combination therapy: a new approach to the treatment of hypertension].

PMID- 10883076
TI  - [The pathogenic mechanism of Helicobacter pylori].

PMID- 10883077
TI  - [Significance of fetal heart rate monitoring during the second stage of labor].

PMID- 10883078
TI  - [Active oxygen radicals, antioxidants and pregnancy].

PMID- 10883079
TI  - [Botulinum toxin in the treatment of cerebral palsy].

PMID- 10883080
TI  - [Developing clinical guidelines for management of severe head injuries].

PMID- 10883081
TI  - [Drug policy].

PMID- 10883082
TI  - [Cardiac myxoma].

PMID- 10883083
TI  - [The terminally ill patient's right to refuse medical treatment according to
      Jewish law].

PMID- 10883085
TI  - [Skoptsi, a cult of self-castrators].

PMID- 10883084
TI  - [At what weight should the low birth weight neonate be circumcised? Medical law
      in the context of ancient days].

PMID- 10883086
TI  - [Hugo Neumann (1858-1912)].

PMID- 10883087
TI  - [Introduction of routine hepatitis A immunization in Israel--the first in the
      world].
AB  - Notification of hepatitis A, which is endemic in Israel, has been compulsory
      since the establishment of the State. From 1992-98 an average of 2,600 cases were
      reported annually. Many infections are asymptomatic and mild, especially in
      children. In general, severity increases with age; in Western countries the case
      fatality rate is 1.5/1,000 among children less than 5 years old and 27/1,000
      among those over 50. Until 1987 incidence in Israel was higher in Jews than in
      non-Jews, but since 1988 incidence has been about 50% higher in non-Jews. Among
      Jews highest age specific rates shifted from children 1-4 years old to children 5
      9 years old in 1970, and in non-Jews in 1989. Improved sanitary conditions and
      personal hygiene have reduced very early childhood exposure and hence increased
      the proportion of susceptible older children and adults, in whom symptomatic
      disease is more prevalent. Israel is the first country in the world to include
      hepatitis A vaccine in its routine immunization schedule. The vaccine is given in
      2 doses: at 18 months and 24-30 months of age, and there will be epidemiologic
      and serologic follow-up. A significant decrease in hepatitis A morbidity is
      expected in small children within 5 years. The percentage of reported cases in
      older children and in adults is expected to increase, although the absolute
      incidence among these groups will decrease.

PMID- 10883088
TI  - [Employment of Russian immigrants in 1998: summary of research and followup
      findings].
AB  - This study examined trends in the employment of immigrant physicians from the
      former Soviet Union. We studied the changes in the proportion of immigrants
      employed as physicians between 1994 and 1998, job characteristics, positions,
      professional status, and improvement in employment characteristics, professional
      status, and in wages due to increased seniority. The study population consisted
      of 7,000 physicians who had immigrated to Israel by June 1992 and had applied to
      the Ministry of Health for medical licensing. Of these, 726 were interviewed in
      1994 and in 1998 all 726 were again approached and 84% were interviewed by
      telephone. Of those interviewed in 1998, 63% were working as physicians, 21% in
      another occupation, and 16% were not working at all. Of those with medical
      licenses, 79% were working as physicians. Of those interviewed in 1994, 93% were
      still employed as physicians in 1998, and 88% of them had been so employed
      continuously. As of 1998, 85% of those interviewed had 5 or more years seniority
      as physicians in Israel, and half had been working for more than 5 years at their
      current place of employment. The best predictor-variable for employment as a
      physician in 1998 was employment as a physician in 1994. The proportions of those
      employed by a public employer, of those earning monthly salaries, and of those
      with a tenured position, were greater in 1998 than in 1994. In 1998, 70% reported
      being employed in a authorized staff position. Funding for the salaries of 75% of
      these physicians came from the budget of their place of employment, not from a
      grant, stipend, or temporary fund for the assistance of immigrants. These
      proportions increased with seniority. The proportions of specialists (22%) and
      residents (37%) had increased in 1998 relative to 1994 (when they were 8% and 23%
      respectively). In addition, since 1994 gross hourly wages had increased with
      seniority in real terms by more than 100%. These findings are evidence of work
      stability and improvement in employment conditions of these immigrant physicians.
      Further, the 1998 follow-up indicated a trend toward becoming "established" and
      improvement in professional status. However, it also revealed models of temporary
      employment, not in compliance with physicians' collective work agreements, a
      situation that warrants examination. It is also important to examine the
      implications of the absorption of so many physicians for medical manpower in
      Israel, and for overall expenditure on health.

PMID- 10883089
TI  - [Type 2 diabetes among adolescents in Israel].
AB  - Type 2 diabetes has been considered rare in children and adolescents. Recently,
      increase in the incidence of type 2 diabetes has been reported among adolescents
      in various parts of the world. We report the occurrence of type 2 diabetes among
      adolescents in Israel. A boy of 14 and girls of 16.5 and 17 were pubertal and
      extremely obese, with a body mass index (BMI) between 39-47 kg/m2. Acanthosis
      nigricans, elevated diastolic blood pressure, and hirsutism with menstrual
      disorders, were associated with insulin resistance, and should raise suspicion of
      type 2 diabetes. Significant obesity and strong family histories of type 2
      diabetes appeared to be important risk factors. Since type 2 leads to long-term
      morbidity and mortality, its early identification and appropriate treatment are
      crucial.

PMID- 10883090
TI  - [Identifying the elderly at risk for falling and accompanying protocols].
AB  - Falling is one of the main problems affecting the health of the elderly. A
      community project was carried out to detect elderly people at high risk for
      falls. One of its aims was also to develop tools allowing primary care
      professionals to detect the elderly at risk for falling. Such a screening test in
      the community-dwelling elderly (EFST) and a protocol for diagnosis and treatment
      of the elderly at risk for falls is presented.

PMID- 10883091
TI  - [Endoscopic sinus surgery for extracranial complications of sinusitis].
AB  - Orbital subperiosteal abscess (SPA) and Pott's puffy tumor (PPT) are the major
      extracranial complications of acute sinusitis. These complications are aggravated
      by the close anatomic relationships between the nasal sinuses and the orbits and
      frontal bone. Furthermore, the rich diploic venous drainage of the region
      enhances the spread of the infection. Between 1992 and 1997, 16 patients (mean
      age 12 years, range 2-15, 10 of them males), 11 of them with SPA and 4 with PPT
      were operated on by the senior author by means of endoscopic sinus surgery (ESS).
      Indications for operation included: CT findings of abscess formation and lack of
      clinical improvement after 48 hours of i.v. antibiotic therapy. Clinical
      resolution of symptoms was achieved in all and there were no operative or
      postoperative complications. We emphasize and explain the advantages of ESS over
      external approaches in surgery for extracranial complications of acute sinusitis
      by several facts: the technique treats the source of the disease, clinical
      success rate is high, morbidity is low, and facial distortion and poor cosmetic
      results completely avoided.

PMID- 10883092
TI  - [Nocturnal eating disorder--sleep or eating disorder?].
AB  - Nocturnal eating disorder (NED) is a rare syndrome that includes disorders of
      both eating and sleeping. It is characterized by awakening in the middle of the
      night, getting out of bed, and consuming large quantities of food quickly and
      uncontrollably, then returning to sleep. This may occur several times during the
      night. Some patients are fully conscious during their nocturnal eating, while
      some indicate total amnesia. The etiology of NED is still unclear, as research
      findings are contradictory. Those suffering from NED exhibit various levels of
      anxiety and depression, and many lead stressful life-styles. Familial conflict,
      loneliness and personal crises are commonly found. Recently, a connection has
      been discovered between NED and unclear self-definition, faulty interpersonal
      communication, and low frustration threshold. Several authors link it to
      sleepwalking, leg movements during sleep, and sleep apnea. Treatment is still
      unclear and there have been trials of pharmacotherapy, psychotherapy, or a
      combination of both. However, pharmacological treatment has generally been found
      to be the most effective, although each case must be considered individually. In
      1998, 7 women referred to our Eating Disorders Clinic, 5% of all referrals, were
      subsequently diagnosed as suffering from NED. Of these, 3 suffered from
      concurrent binge-eating disorder and 4 also from bulimia nervosa. 2 case studies
      representative of NED are presented.

PMID- 10883094
TI  - [Emergency cesarean section in a comatose parturient after head trauma].
AB  - Coma in pregnancy and labor is a rare and complicated situation. One of the
      causes is severe head trauma, which requires neurosurgical consultation and
      possibly urgent transfer to a neurosurgical unit. This should follow
      stabilization, confirmation of fetal viability, and cesarean section when
      indicated. A 38-year-old primigravida at term and in labor, with severe head
      injury from a vehicular accident is reported. Emergency cesarean section was
      performed for severe fetal distress during resuscitation. Fetal distress in a
      comatose parturient with severe head injury may require a short delay in referral
      to a tertiary trauma center to allow for an emergency cesarean section.

PMID- 10883093
TI  - [Botulin toxin for spasticity in spinal cord damage by treating the motor
      endplate].
AB  - Therapeutic injection of botulin toxin is well-recognized for reducing tonus in
      local dystonia. However, its efficacy in reducing spasticity in spinal cord
      injuries is still unproven. 4 men and 1 woman (mean age 39 years, range 20-56)
      with spinal cord injury and debilitating spasticity, and no response to standard
      treatment for spasticity received injections of botulin, 200-300 U, into 4-8
      points in their legs to block muscle-nerve synapses. In all 5 tonus was reduced
      in the area of the block, while in some it was also reduced in more distal
      muscles. In 1 there was reduced tonus in both the injected and contralateral leg.
      The therapeutic effect on tonus persisted for 3 months. In spite of objective
      improvement in tonus in all 5, only 3 felt subjective improvement, but in none
      was there improvement on standard functional scaling. We found injection of
      botulin toxin effective in reducing tonus in the spinal cord-injured, and to some
      extent in improving subjective feeling of well-being in some of them. Objective
      measurement might show functional improvement after larger doses of toxin
      injected into more muscles. This might be necessary because the muscle mass of
      the legs is large and the intensity of involuntary contraction is especially high
      in these patients.

PMID- 10883096
TI  - ["Stigma 2000"--is a change of direction really necessary?].

PMID- 10883095
TI  - [Anaphylactic shock after diclofenac sodium (Voltaren)].
AB  - Anaphylaxis due to diclofenac sodium (Voltaren) is rare. We describe a 39-year
      old woman who received a suppository of diclofenac for analgesia 6-hours after
      cesarean section. She developed severe angioedema and profound hemodynamic shock
      10 minutes after the diclofenac, to which she had been exposed in the past
      without any side-effects. There are few reports of such an acute, life
      threatening, multisystem reaction to this drug in the English literature.

PMID- 10883097
TI  - [Interaction between oral anticoagulants and dietary factors].

PMID- 10883098
TI  - [Mitochondrial diseases: molecular genetics and clinical applications].

PMID- 10883099
TI  - [Depression and coronary artery disease risk].

PMID- 10883100
TI  - [Central alveolar hypoventilation in adults--Ondine's curse].

PMID- 10883101
TI  - [Characteristics and implications of emotional abuse in children and
      adolescents].

PMID- 10883102
TI  - [Danger of sports for cardiac patients].

PMID- 10883103
TI  - [Gastroparesis: the syndrome of stomach paralysis].

PMID- 10883104
TI  - [Mini-mental state examination: translation into several languages].

PMID- 10883105
TI  - [Femoral shaft fractures in children and adolescents].

PMID- 10883106
TI  - ["I am of the family of Dorkati"--about virginal blood and menstruation in our
      sources)].

PMID- 10883107
TI  - [Isaac Arthur Abt (1867-1955)].

PMID- 10883108
TI  - [Early detection of glaucoma by a mobile unit--results from 10,000 examinees].
AB  - Glaucoma, the third leading cause of blindness in the western world, is
      characterized by painless, gradual loss of visual fields which may lead to severe
      visual impairment or even blindness. In 4 years of operation of a mobile glaucoma
      unit for screening and early diagnosis of glaucoma, 10,037 subjects aged 18-95
      years were screened (4504 women, 45%); 55% were under 50 years (Graph 1). Ocular
      hypertension was diagnosed in 8.0%; primary open angle glaucoma (POAG) in 0.8%,
      with 2/3 already under treatment, the rest newly diagnosed. Pseudo-exfoliative
      glaucoma was diagnosed in 0.2%; only 2 cases had closed angle glaucoma; 91% of
      those screened were normal (Fig. 4; age stratification, Graph 3). POAG increased
      with age, from 0.2% in those under 40 years to 10% in those over 80; POAG was
      more common in men, but OHT was similar in both sexes (6.0% vs. 5.3%). There was
      no correlation between incidence of POAG and place of work except in the Sorek
      Nuclear Center (1.9% vs. 0.8%, p = 0.11). Other conditions significantly more
      frequent in POAG than normals were diabetes mellitus (x 2.5), systemic
      hypertension (x 4), myopia (x 2) and history of intraocular surgery (x 6).

PMID- 10883109
TI  - [Causes of blindness in Israel].
AB  - Of the world population, 38 million are blind and another 110 million are
      visually impaired. Even in the developed countries there are 3.5 million who are
      blind. This study of blindness in Israel is based on the National Blind Registry.
      At the end of 1998, 15,937 were registered as blind, 0.3% of the total
      population; 776 (5%) of them were 18 years old or younger; 6,426 (40%) 18-65
      years old; and 8,735 (55%) 65 years or older. The leading causes of blindness in
      Israel are glaucoma (2,074, 13%), macular degeneration (1,954, 12%) and diabetes
      mellitus (1,680, 11%). Since glaucoma and diabetes, and to a lesser extent
      glaucoma, respond to treatment, blindness could have been avoided in most cases.
      National screening programs for early diagnosis and treatment of these diseases
      would reduce prevalence of the newly blind.

PMID- 10883110
TI  - [Cortical blindness following coronary angiography].
AB  - Cortical blindness has been occasionally reported as a complication after
      cerebral angiography, but is rare after coronary angiography. The contrast agent
      is believed to be responsible for the sudden development of blindness. Although
      the exact mechanism is unknown, it appears that the contrast agent disrupts the
      blood brain barrier, mostly in the occipital areas. We report a 77-year-old man
      who suddenly developed transient, bilateral cortical blindness 4 hours after
      coronary angiography. Using contrast enhancement, the CT scan showed typical,
      symmetrical involvement of both occipital lobes. There were no other neurological
      deficits. Vision and CT findings returned to normal within 48 hours.

PMID- 10883111
TI  - [Microlaparoscopy in diagnostic and operative gynecologic procedures].
AB  - A recent further development in laparoscopic surgery is microlaparoscoopy. The
      technique is identical to standard 10 mm laparoscopy except for the use of small,
      2 mm scopes and trocars. We used this technique in 19 patients treated from June
      1998 to February 1999. The advantages of microlaparoscopy are: smaller incisions,
      less risk of damage to pelvic organs and less postoperative pain. However, the
      use of microlaparoscopy for operative procedures is limited to simple operations
      due to the limited field of vision. We urge our colleagues to consider
      microlaparoscopy whenever diagnostic laparoscopy is needed.

PMID- 10883112
TI  - [Management of compound high energy injuries of the limbs--lessons and
      recommendations].
AB  - We treated 49 patients with high energy injuries of the limbs between 1.1.94
      31.12.97. They had sustained 61 fractures, 50 of which were open; 14 had
      bilateral injuries, and 3 had lost a limb. All fractures were stabilized on
      arrival with an A-O tubular external fixator. Soft tissue loss was covered by a
      combination of split skin graft and tissue flaps following repeated surgical
      debridement. After 10 days, or when all soft tissue defects were covered, the
      cantilever external fixation frame was exchanged for a hybrid ring which provided
      three-dimensional stability and allowed early full weight bearing and joint
      mobilization. The hybrid ring frame did not interfere with the care of soft
      tissue injuries. Furthermore, it kept the risk of developing deep infections to a
      bare minimum. At follow-up after a median of 20 months, 1 patient had developed
      osteomyelitis but all had returned to independent function.

PMID- 10883113
TI  - [Prioritizing suspected diagnosis of both brain and abdominal injuries--is it a
      problem?].
AB  - Current guidelines for management of suspected head and abdominal injuries are
      based on retrospective studies like that of Wisner & al, Following a recent
      review in this journal by Y. Kluger & al, which was based on non-Israeli data, we
      decided to define the current status at our trauma center. We compare our data of
      18 months of hospital admissions for acute trauma in which head CTs were done
      with those of 5 articles advocating specific protocols for decisions in pre
      laparotomy diagnosis. In the 861 cumulated cases, compared with the 800 of Wisner
      & al, craniotomy was required in 15% vs 7% (p < 0.05); laparotomy was much less
      frequent, 2.7% vs 12.9% (p < 0.05). The chance of finding a case requiring both
      craniotomy and laparotomy was 1 in 300. As the clinical condition of multiple
      trauma involving the head and abdomen is becoming less frequent and includes
      diverse situations, a comprehensive algorithm might be inaccurate. Good clinical
      judgment of the clinician and teamwork are therefore preferable.

PMID- 10883114
TI  - [Incidence of insulin dependent diabetes in youth in Israel in 1997: Israel IDDM
      Registry Study Group for incidence of diabetes between the ages of 0-17].
AB  - Recent reports from different countries have shown an increasing incidence of
      insulin-dependent diabetes mellitus (IDDM, type I diabetes). In Israel, several
      surveys of the incidence of IDDM have been conducted. During 1996, a national
      juvenile diabetes register was founded by specialists in endocrinology, and the
      Israel Center for Disease Control (ICDC). This is the first report of the
      national incidence of IDDM in the 0-17 year age group in Israel. New cases of
      juvenile diabetes were reported using an anonymous form. The ICDC was responsible
      for data collection, control and statistical analyses. During 1997, 162 new cases
      of diabetes mellitus were reported in the age group 0-17, 154 of them diagnosed
      as IDDM. The annual incidence in the total population of Israel in 1997 was
      7.7/100,000. Age-specific incidence was 7.3/100,000 in boys and 8.1 in girls. A
      family history of IDDM was found in 14.3% of the cases. Incidence was higher for
      Jews (9.2/100,000) than Arabs (3.6/100,000). Among Jews, children whose fathers
      were born in Yemen had the highest incidence and those born to fathers born in
      Israel the lowest incidence. IDDM incidence rates for 1997 are higher than
      reported in previous surveys. It will be possible to draw conclusions regarding
      possible trends in incidence from data to be gathered in the next few years.

PMID- 10883115
TI  - [Phenobarbital coma for psychogenic status epilepticus].
AB  - Among patients seen for epileptic seizures, there is a subgroup of those who do
      not have epilepsy but suffer from psychogenic paroxysmal events which mimic
      epileptic seizures. The differential diagnosis between them is of the utmost
      importance, as incorrect diagnosis of seizures subjects the patient to incorrect
      management. In the case psychogenic status epilepticus, the treatment may
      endanger the patient. We report 3 women, aged 20, 20 and 28 and a man aged 24
      with psychogenic status epilepticus admitted to an intensive care unit and
      treated by induction of phenobarbital coma when other antiepileptic medication
      failed.

PMID- 10883116
TI  - [Sclerosing mesenteritis--an unusual cause of abdominal pain].
AB  - Sclerosing mesenteritis (SM) is rare and fewer than 300 cases had been reported
      up to 1997. We describe a 29-year-old woman who had abdominal pain for 1 year and
      presented with a palpable abdominal mass. The diagnosis of SM was made only after
      diagnostic laparoscopy and biopsy of the peritoneum.

PMID- 10883117
TI  - [New global horizons in the drug development process: the International
      Conference on Harmonization].

PMID- 10883118
TI  - [Quality of life in patients with automatic implantable cardioverter
      defibrillator (AICD)].

PMID- 10883119
TI  - [The inflammatory response to open heart surgery and cardiopulmonary bypass].

PMID- 10883120
TI  - [Are filters necessary in pulmonary function tests? Recommendations of the
      Israeli Society for Pulmonary Diseases].

PMID- 10883121
TI  - [Lumbar spinal stenosis: diagnosis and treatment].

PMID- 10883122
TI  - [The need for preoperative biliary drainage in the jaundiced patient].

PMID- 10883123
TI  - [Sensory symptoms and pain in Parkinson disease].

PMID- 10883124
TI  - [Role of the pharmacist in a modern health care system].

PMID- 10883125
TI  - [The use of methylene blue in critical care].

PMID- 10883126
TI  - [Smoking by an Israeli general hospital staff, and attitude to smoking in
      hospitals. Are we in Israel ready to institute "smoke-free hospitals"?].
AB  - Smoking within hospitals is common in general hospitals in Israel. It has a
      strong negative educational impact, has a negative image and curing its ill
      effects help keep our hospitals busy. An anonymous questionnaire was answered by
      128 members of our hospital staff (28%). Their distribution, according to
      occupation and sex was representative of the rest of our hospital staff. 19% of
      our workers are smokers, a much lower proportion than in our general adult
      population. The proportion was highest among maintenance (40%) and sanitary-help
      staff (36%). 23% of nurses and 15% of physicians were smokers. This situation is
      better than that among Italian or Japanese medical staff, but much worse than
      among North American medical staff. 75% of our workers who smoke declared that
      they smoke outside the room in which they work. 66% and 72% of the staff believe
      that hospital workers and visitors, respectively, should smoke outside hospital
      buildings. Only 19% of all workers do not believe that a "smoke-free hospital" is
      attainable. 34% believe that a "smoke-free hospital" is achievable, and 47% said
      that it is perhaps achievable. 86% of all the workers, and 41% of the smokers,
      expect the hospital director to implement an effective policy of enforcing the
      law limiting smoking within hospitals (and other public buildings) in Israel. 60%
      are willing to contribute actively to this effort. We believe these results
      strongly suggest that the time is ripe for implementation of the "smoke-free
      hospital" in Israel. This requires a strong and effective central policy, like
      that in the USA. We suggest measures that the Israel Ministry of Health take
      measures to successfully implement this policy.

PMID- 10883127
TI  - [Alfred Fabian Hess (1875-1933)].

PMID- 10883128
TI  - [The Israeli trial with cilazapril (Vasocase) for the treatment of hypertension-
      summary of the care of 413 patients in a community health setting].
AB  - In a multicenter study in community clinics, 413 patients with mild to moderate
      essential hypertension were treated with cilazapril (Vasocase), 2.5 mg daily.
      Patients had either been untreated or had developed side-effects from previous
      antihypertensive treatment. When response was inadequate the dose was either
      increased to 5 mg or another antihypertensive medication was added, or both.
      Treatment significantly reduced systolic and diastolic blood pressures. Pulse
      rate decreased significantly from the second month of treatment onwards. At the
      end of the 3rd month of treatment blood pressure was normalized or had decreased
      by more than 10 mmHg in 91.9% of patients. Physicians' evaluations revealed
      improvement in 62%; patients' self-evaluations suggested improvement in 61%.
      Efficacy was equal in all age groups and in both obese and nonobese patients.
      Antihypertensive response was superior in those with normal renal function. Side
      effects were rare and similar to those reported in the literature.

PMID- 10883129
TI  - [Israeli family physicians' attitudes to clinical guidelines for treatment of
      diabetes].
AB  - Clinical guidelines are systematically developed statements designed to help
      practitioners and patients make decisions about appropriate health care for
      specific clinical states. Attitudes of family physicians to clinical guidelines
      for treating diabetes and guidelines in general were evaluated from anonymous
      questionnaires answered by physicians participating in continuous medical
      education throughout the country (May-June 1998). The questionnaire dealt with
      attitudes to the recently published specific guidelines for treating the diabetic
      patient and overall perception of the efficacy of clinical guidelines. 293 family
      physicians, aged 40.2 +/- 7.0 responded (83%). 93.5% appreciated the guidelines
      and thought them applicable. Most (83.7%) reported the guidelines to be of help
      in their daily work; 31.4% said they were oversimplified; a quarter said they
      aimed mainly at containing costs. Most respondents preferred written guidelines
      of up to 5 pages. In view of our results, attention can now be turned to
      developing ways to implement the guidelines. To improve adherence, they need to
      be short and the rate of publication of new clinical guidelines should be slowed.

PMID- 10883130
TI  - [Unconventional treatment of severe heart failure in the elderly].
AB  - In the elderly, congestive heart failure is common and associated with
      significant morbidity and mortality. Comprehensive management of heart failure
      improves functional status and decreases mortality. Diuretics remain the mainstay
      in treating congestive heart failure. However, some patients are resistant to
      diuretics. This is a serious problem as it seems to represent a final
      manifestation of congestive heart failure. In an 85-year-old woman diuretic
      resistance was recognized as the cause of failure of conventional diuretic
      therapy. When the dose of furosemide was rapidly increased from 120 mg per os to
      1000 mg i.v. within 4 days, diuresis began and there was dramatic improvement in
      her condition. The dose was then gradually decreased until a conventional
      maintenance dose of 200 mg/day per os was reached. This dose was sufficient to
      keep her heart failure under control.

PMID- 10883131
TI  - [Syme amputation of the foot--is it appropriate for foot infections in
      diabetics?].
AB  - Syme ankle disarticulation for foot infections in diabetics with concomitant
      peripheral vascular disease is often unsuccessful. The need for re-amputation
      usually results from recurrent infection or ischemia of the posterior heel flap.
      We present 5 such cases of deep foot infections in diabetics who underwent Syme
      amputation after failure of local debridement. All patients needed reamputation
      in 4-18 days for ischemia of the flap.

PMID- 10883132
TI  - [Favorable outcome of hyperacute epidural hematoma in an octogenarian].
AB  - Acute epidural hematoma is very rare in the elderly after head injury. It is
      usually associated with extremely high mortality or severe disability. In an 87
      year-old woman a large, hyperacute, epidural hematoma was diagnosed. She was
      treated promptly and enjoyed an uneventful, complete recovery. This exceptional
      case should encourage an intensive approach even in seemingly minor head trauma
      in the elderly.

PMID- 10883133
TI  - [Tubulo-interstitial nephritis and uveitis syndrome--TINU syndrome].
AB  - Acute tubulo-interstitial nephritis and uveitis (TINU syndrome) in a 53-year-old
      woman is reported. This rare syndrome was described 27 years ago by Dobrin et al.
      Since then about 50 cases have been described. The syndrome can appear at any age
      but most patients are under 20 years; about 75% are females. Clinical
      characteristics include fatigue, general malaise, weight loss, fever, night
      sweats, anorexia, nausea and vomiting, pallor, nocturia, polyuria, arthralgia and
      skin rash. Ocular involvement usually includes anterior uveitis but is sometimes
      posterior; in most cases the uveitis is bilateral. The characteristic laboratory
      findings are anemia, rapid sedimentation rate, decreased glomerular filtration
      rate with increased serum creatinine and urea. Total protein is increased because
      of polyclonal gammopathy and elevated beta 2-microglobulin. Urinalysis
      characteristically reveals proteinuria and beta 2-microglobulinuria. The
      histopathologic features on renal biopsy are characteristic of tubulo
      interstitial nephritis. Uveitis can precede, accompany or follow onset of the
      nephropathy. The pathogenesis and etiology of the syndrome are as yet unknown.
      Treatment consists of large doses of corticosteroids, but the necessity for
      treatment is unclear, since there is evidence of spontaneous improvement.
      Although the prognosis of the nephropathy is favorable and most cases are
      reversible, the uveitis tends to recur.

PMID- 10883134
TI  - [Pulmonary involvement in Osler-Weber-Rendu syndrome].
AB  - Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is a group of
      autosomal dominant diseases with variable penetration, characterized by vascular
      malformations. Recently hereditary hemorrhagic telangiectasia has been found to
      be a phenotypic expression of mutations in genes located on chromosomes 9 and 12,
      and possibly of other genes located on other chromosomes. We describe 2 patients
      with hereditary hemorrhagic telangiectasia and pulmonary involvement who
      presented with repeated complaints of dyspnea and cyanosis and were diagnosed as
      having long-standing asthma. Both were treated with therapeutic catheterization
      and embolization with good clinical outcomes.

PMID- 10883135
TI  - [Involvement of drug manufacturers in controlled research].

PMID- 10883136
TI  - [Gestational diabetes--past, present and future. Recommendations of the Fourth
      International Workshop Conference on Gestational Diabetes Ching (1997) and the
      Multinational Multicenter Study (NIH-HAPO Study) for solving the problem].

PMID- 10883137
TI  - [Should laparoscopy play a role in gynecological oncology?].

PMID- 10883138
TI  - [Prophylactic oophorectomy during abdominal and pelvic surgery: an essential or a
      superfluous procedure?].

PMID- 10883139
TI  - [Prophylactic oophorectomy in colorectal cancer].

PMID- 10883140
TI  - [Sport injuries in children and adolescents].

PMID- 10883141
TI  - [Pelvic triple osteotomy as a treatment for hip dysplasia].

PMID- 10883142
TI  - [Growth disturbances in children with juvenile rheumatoid arthritis].

PMID- 10883143
TI  - [Immunological aspects of the involvement of Coxsackie B viruses in juvenile
      diabetes and cardiomyopathy].

PMID- 10883144
TI  - [Etiology, pathogenesis and treatment of seborrheic dermatitis].

PMID- 10883145
TI  - [Telling bad news].

PMID- 10883146
TI  - [Internal medicine in the third millennium--where is it going? I accuse!].

PMID- 10883147
TI  - [Cannabis--a drug with dangerous implications for mental health].
AB  - Accepting and forgiving attitudes to the use of cannabis in its various forms,
      such as marijuana or hashish, are not justified, as they may result in dangerous
      mental health consequences. A theoretical framework for this opinion is provided,
      including information on the various forms of cannabis available. Case studies
      presented exemplify possible complications resulting from use of cannabis or its
      derivatives.

PMID- 10883148
TI  - [Military doctors killed in action during the War of Independence while serving
      as doctors].

PMID- 10883149
TI  - [Simon Van Creveld (1894-1971)].

PMID- 10883150
TI  - [Solitary pulmonary nodule of unknown origin].

PMID- 10883151
TI  - [Autologous chondrocyte transplantation--from science fiction to routine clinical
      practice].
AB  - Adult articular cartilage lacks the capacity for self-repair. The limiting factor
      appears to be the inability of chondrocytes to proliferate while embedded in the
      extracellular matrix typical of hyaline cartilage. Cartilage defects larger than
      1 cm2 change articular biomechanics and lead to eventual osteoarthritis and joint
      destruction. During the past decade, several competing techniques have evolved to
      stimulate articular cartilage repair. Small lesions can be successfully treated
      by either micro-fracture or osteochondral cylinder grafting. The latter technique
      allows immediate weight bearing but leads to damage of previously uninvolved
      areas of articular cartilage, which limits its application to lesions of less
      than 2 cm2. When the damaged area is more extensive, grafting of autologous
      chondrocytes should be considered. First a diagnostic arthroscopy is performed to
      assess the damaged area and a small cartilage biopsy is taken. 6 weeks later,
      arthrotomy and chondrocyte transplantation are performed. In the interval, the
      antologous chondrocytes have expanded by 2 to 3 orders of magnitude. Our
      experience to date includes 10 cases with follow-up of 6 months to 5 years.
      Preoperative complaints of crepitation and locking disappear. There is functional
      improvement and pain reduction of approximately 50%. This procedure, currently
      limited to patients under 55 years of age with limited damage to an articular
      surface, for the first time allows reconstruction of damaged articular areas
      without resorting to allografts.

PMID- 10883152
TI  - [High dose endobronchial brachytherapy for malignant airway obstruction: first
      study of 30 patients].
AB  - Brachytherapy is especially suitable for palliative treatment of endobronchial
      tumors adjacent to internal organs that might be damaged by intensive external
      beam radiation, but are easily accessed with a flexible bronchoscope. This
      treatment is mostly palliative. 30 patients underwent such palliative high-dose
      endobronchial brachytherapy to alleviate malignant airway obstruction. With the
      aid of a flexible fiberoptic bronchoscope an endobronchial catheter was inserted
      adjacent to the tumor and treatment delivered using a 192Ir remote afterloader
      for 5-10 min, in 2 or 3 sessions. There was symptomatic improvement in 26 (86%)
      and objective improvement in 27 (90%). 1 patient died of hemoptysis.

PMID- 10883153
TI  - [Carbon dioxide gas embolism during laparoscopic cholecystectomy].
AB  - A case of carbon dioxide gas embolism during laparoscopic cholecystetomy is
      presented. Prompt diagnosis and immediate treatment resulted in positive outcome.
      Laparascopic cholecystectomy is nowadays one of the most common operations for
      cholecystectomy and certainly the most frequent endoscopic surgical procedure. It
      is usually safe and effective. However, a number of serious complications have
      been reported during the procedure. Gas embolism is one of the complications that
      may occur during the initial gas insufflation or during dissection of the gall
      bladder. Symptoms are mainly related to the speed and the amount of gas that
      reaches the venous system. Early recognition and prompt treatment are required to
      prevent severe morbidity or even fatal outcome. Transesophageal echocardiography
      has detected many unsuspected cases of gas embolism. However, capnograph
      monitoring of end-tidal CO2, routinely used in everyday anesthesia, is highly
      reliable in alerting to the possibility of gas embolism and also in confirming
      its occurrence. In cases of suspected gas embolism close collaboration between
      anesthetist and surgeon is required.

PMID- 10883154
TI  - [Physicians' assessment of computerized prescribing].
AB  - Prescription errors are a major source of preventable adverse drug events.
      Computerized prescribing (CP) which screens physicians' order for mistakes, drug
      allergy, drug-disease, drug-laboratory and drug-drug interactions can prevent
      many of these errors and improve quality of care. However, computerized systems
      are often time-consuming, difficult to handle, and may create their own mistakes.
      Following the introduction of CP on an internal medicine ward, we administered a
      questionnaire to evaluate physicians' opinions about the new system. The survey
      assessed computer literacy, ease of using CP, effects on time management, opinion
      of users regarding error prevention, and usefulness of the information provided.
      Opinions were generally favorable; most users felt that CP makes their work more
      accurate, reduces errors, is easy to learn and to use, and provides important and
      useful information. Physicians were most critical of equipment failure and drugs
      and dosages not included in the CP program, a result of rapid development of the
      system. Errors resulting from the use of CP were considered minimal. Comparison
      of physicians, with and without previous experience with computer work, as well
      as local and foreign graduates, revealed minor differences. But once physicians
      learn to work with a well-organized CP system and computerized work stations,
      they appreciate the order, safety and knowledge they provide.

PMID- 10883155
TI  - [Presurgical neuropsychological assessment in epilepsy: the Wada test].
AB  - 37 candidates for epilepsy surgery underwent the intracarotid amytal procedure
      (IAP; also known as the Wada test) to determine hemispheric speech dominance and
      memory capacity. 31 demonstrated left hemisphere speech dominance, 2 showed
      evidence for bilateral language and 4 demonstrated right hemispheric language
      dominance. Our study supports a correlational relationship between handedness,
      lesion laterality and age of onset of seizures, as reported in earlier studies.
      Left-handed patients with a left hemisphere lesion whose seizures began to an
      early age had a strong tendency for reversed language dominance. Asymmetry of at
      least 20% in performing the memory test was taken as the cutoff score for
      demonstrating laterality of lesions. The asymmetry score correctly predicted
      laterality of lesions in all 28 patients; 6 did not have asymmetry scores and 3
      were examined for language only. None of the patients who successfully passed the
      Wada memory test had any significant postsurgical memory deficits; 1 had
      transient reduction in verbal memory and 4 who did not pass the test were not
      operated on for this reason. Our results demonstrate the importance of the Wada
      test in determining cerebral speech dominance, in predicting post-surgical
      amnesia, and support its usefulness in predicting laterality of seizure focus in
      candidates for temporal lobectomy.

PMID- 10883156
TI  - [Examining the connection between physical exertion in pregnancy and premature
      birth].
AB  - The relationship between physical activity at home and at work during pregnancy
      and preterm birth was studied. Using a case-control design, 99 women who
      delivered preterm were compared with 189 women who had term deliveries. The risk
      of preterm birth was tested in relation to characteristics of work in and outside
      the home. All women were interviewed post-partum before discharge. There were no
      statistically significant differences between the groups in relation to
      sociodemographic and obstetrical factors, but level of education was
      significantly lower in the study group versus the control group (p = 0.001).
      Women who delivered preterm had devoted less time 3 months prior to delivery to
      household chores (mean of 3.7 hours vs. 4.8 hours in the control group, p =
      0.002). They also had spent less time walking around the home than the controls
      (1.2 vs. 1.5 hours, p = 0.02). There were no differences between the groups in
      relation to physical activity outside the home, not during working hours, nor in
      duration of work. Significantly fewer women who delivered preterm were active in
      sports (odds ratio 0.22; 95% confidence interval 0.50-0.65; p = 0.002). A low
      level of education was significantly related to the risk of preterm birth, which
      may have resulted from lesser compliance with their physician's recommendations.
      It appears that in women not used to significant physical activity but who had
      access to adequate prenatal care, physical effort during pregnancy was not
      related to a higher risk of preterm birth.

PMID- 10883157
TI  - [Transient ischemic ECG changes in a patient with acute cholecystitis without a
      history of ischemic heart disease].
AB  - That abdominal distention, nausea, and chest pain may be accompanied by ischemic
      ECG changes is well known and has been described in the literature. However, very
      few cases have been reported with acute cholecystitis and ECG changes not due to
      cardiac ischemia. We present a previously healthy 20-year-old woman admitted with
      acute cholecystitis. Prior to surgery routine ECG showed ST-depression and T-wave
      inversion. The day following cholecystectomy the ECG returned to normal. 1 month
      later, ergometry and echocardiography were both negative. Based on the literature
      and our personal experience, although ECG changes may occur in acute
      cholecystitis, the possibility of cardiac ischemia must be excluded. However,
      when no cardiac basis is found, ultrasound of the biliary system might reveal the
      cause of these ECG changes. Thus, in acute cholecystitis with ischemic ECG
      changes but no other laboratory or clinical evidence of cardiac ischemia, ECG
      changes alone are not a contraindication to cholecystectomy. Furthermore, delay
      in treatment could be harmful.

PMID- 10883158
TI  - [GAG for osteoarthritis of the knee--a prospective study].
AB  - Osteoarthritis results from progressive catabolic loss of cartilage proteoglycans
      due to imbalance between synthesis and degradation. The availability of
      glucosamine, an intermediate in mucopolysaccharide synthesis, can be rate
      limiting for proteoglycan production in cartilage tissue culture. 57 patients
      suffering from osteoarthritis of the knee were randomized into a group treated
      for 4 weeks with daily i.v. glucosamine sulfate (GS) together with 800 mg
      chondroitin sulfate, and a placebo group. Knee pain at rest, on movement and on
      palpation, as well as range of knee motion were then recorded. In the GS group,
      there was significant reduction of clinical symptoms (p < 0.01), but no
      significant reduction in the placebo group. Physicians' assessment of tenderness
      and range of motion were significantly in favor of the GS group (p < 0.01). In
      those treated with glycosamine there were no adverse reactions and no changes in
      laboratory blood tests. We conclude that GS can be considered the drug of choice
      for prolonged treatment of osteoarthritis.

PMID- 10883159
TI  - [Opiate addiction as a chronic brain disease: new concept of an old problem, and
      re-evaluation of methadone treatment].

PMID- 10883160
TI  - [Herceptin].

PMID- 10883161
TI  - [The Israel Freedom of Information Law, 1998: implications with respect to the
      health care system].

PMID- 10883162
TI  - [Electronic presentation--a variegated tool for improving quality of medical
      lectures and presentations].

PMID- 10883163
TI  - [Unstable angina pectoris].

PMID- 10883164
TI  - [Intramedullary nailing of the femur].

PMID- 10883165
TI  - [Chemoradiotherapy: innovation in treatment of high-risk cervical cancer].

PMID- 10883166
TI  - [Aquaporins (water channels): physiology and pathophysiology].

PMID- 10883167
TI  - [The toxic patient as a potential organ donor].

PMID- 10883168
TI  - [Latex allergy as a life-threatening danger in children: importance of increased
      awareness of this phenomenon].

PMID- 10883169
TI  - [von Hippel-Lindau disease].

PMID- 10883171
TI  - [Camptocormia].

PMID- 10883170
TI  - [Current management of bladder exstrophy].

PMID- 10883172
TI  - [Shunamitism].

PMID- 10883173
TI  - [Henry Koplik (1858-1927)].

PMID- 10883175
TI  - [Eating disorders in early adolescence--study from the section on young
      adolescent nutrition in Jerusalem].
AB  - Young adolescents were assessed with regard to cognitive, socio-cultural and
      behavioral components of eating disturbances. An anonymous questionnaire was
      administered to 5th-8th grade pupils, 280 girls and 251 boys, to assess eating
      habits, body image, self-confidence, environmental-cultural influences, risk
      behaviors and socio-economic state. Girls scored consistently higher on all
      weight-control behaviors. Discontent with own body, and attitudes and behaviors
      associated with eating disorders, were reported by under-studied populations such
      as boys and younger girls. Both frequency and severity of weight-control
      behaviors were associated with "social age." Highly significant differences
      between scores of 6th and 7th graders indicate that they may be at a time of
      increased susceptibility. Measuring the influence of the mass media gave
      inconsistent results.

PMID- 10883174
TI  - [Non-penetrating deep sclerectomy without collagen implant for glaucoma, as
      single or combined surgery].
AB  - Deep sclerectomy (DS) can be used in glaucoma with increased intraocular pressure
      when medical treatment fails. It involves removing part of the ocular drainage
      apparatus. Resistance to intraocular fluid drainage is decreased, improving
      drainage and decreasing intraocular pressure. By avoiding anterior chamber
      penetration, DS diminishes frequency of the complications of filtering surgery.
      24 eyes of 23 patients underwent DS for primary or secondary open angle glaucoma
      with elevated intraocular pressure not controlled medically. It included
      preparation of a 4.0 x 4.0 mm limbal-based external scleral flap, dissecting and
      removing most of an internal scleral flap (leaving it 1 mm smaller than the
      external flap), unroofing Schlemm's canal and removing fine endothelial tissue
      lining its inner walls. The external scleral flap was then repositioned and
      sutured. Collagen implants were not used. In some cases DS was combined with
      extracapsular cataract extraction and intraocular lens implantation. Mean
      intraocular pressure decreased from 24.8 +/- 3.9 mmHg initially to 12.8 +/- 4.4
      mmHg 6 months after operation (p < 0.0001). There was no difference in
      postoperative intraocular pressure between DS as a single procedure or as part of
      a combined operation. Complications were mild and of short duration. If long-term
      follow-up shows that lowered intraocular pressures are maintained, DS should be a
      surgical option in earlier stages of glaucoma.

PMID- 10883176
TI  - [Laparoscopic adrenalectomy].
AB  - Constant advances and increasing experience in laparoscopic surgery renders it
      applicable for adrenal surgery. The wide exposure required for open adrenal
      surgery makes this minimally invasive procedure an attractive and advantageous
      alternative. Between 1996-1999, we performed 35 laparoscopic adrenalectomies in
      30 patients 20-72-years old. Indications included: Conn's syndrome--14,
      pheochromocytoma--11, Cushing's syndrome--6, nonfunctioning adenoma--3, and
      metastatic sarcoma--1. 5 underwent bilateral laparoscopic adrenalectomy. In 3
      (8.5%) the procedures were converted to open operations. Overall morbidity was
      13% and there was no mortality. Mean operative time was 188 minutes, but only 130
      in our last 10 cases. Mean hospital stay was 4 days and they returned to normal
      activity an average of 2 weeks later. According to our study and previous
      reports, laparoscopic adrenalectomy is feasible and safe and it may soon become
      the procedure of choice for adrenal tumors.

PMID- 10883177
TI  - [Gastrointestinal bleeding in children--etiology and diagnosis. Survey of
      patients in a Tel Aviv medical center, in the years 1990 to 1997].
AB  - During 1990-1997 we investigated 201 children with gastrointestinal bleeding.
      Average age was 3.9 +/- 6 years; 57.2% were males. There were 129 (64.2%) cases
      of lower and 72 (35.8%) of upper GI bleeding. Complications of upper GI bleeding
      were more severe than those of the lower: 6 of 8 (75%) patients who deteriorated
      into hypovolemic shock had upper GI bleeding; 40 of 50 (80%) who required i.v.
      fluids (crystaloids and/or blood) had also bled from the upper GI tract; but
      anemia was more frequent (27.7% vs 17%) in lower GI bleeding. The main etiology
      for upper GI bleeding was peptic ulcer, and for lower GI bleeding anal fissure.
      Mean hospital stay for upper GI bleeding was 3.87 +/- 2.61 days vs 3.40 +/- 3.51
      for lower (not significant). In 34% the etiology of bleeding was undetermined.
      Although current literature refers to intussusception as a common cause of GI
      bleeding in infancy, we had no such cases. This difference might have resulted
      from our diagnoses being made earlier, before mucosal damage could have caused
      bleeding. We found polyps the second most frequent cause for lower GI bleeding in
      children. Endoscopy was of more benefit than any other diagnostic method, while
      barium enema and ultrasound had no diagnostic value. Stool culture did not
      contribute to diagnosis: only 3 of 36 were positive, so it is only necessary when
      there is bloody diarrhea.

PMID- 10883178
TI  - [Acute ischemia of the lesser gastric curvature--a rare marker of sclerotic
      disease].
AB  - The rich blood supply of the stomach protects it from ischemia and necrosis.
      Acute gastric ischemia, an emergency with high mortality, is rare.
      Atherosclerosis is the leading cause of acute ischemia, and the lesser curvature
      of the stomach is more vulnerable due to its relatively lesser blood supply.
      Reduction in gastric blood supply usually presents as chronic disease
      characterized by gastritis, gastric ulcer, or gastroparesis. Gastroscopy can
      identify lesions of the gastric mucosa, and angiography demonstrates occluded
      vessels. Treatment of acute gastric ischemia is surgical, with total gastrectomy
      preferred over partial resection.

PMID- 10883179
TI  - [Elective repair of infra-renal aortic aneurysm in octogenarians].
AB  - Age over 80 years is generally considered an independent risk factor in elective
      surgery for abdominal aortic aneurysm (AAA). As the general population increases
      in age, more elderly are likely to be candidates for such surgery. We studied
      prospectively 100 consecutive patients undergoing elective AAA surgery between
      1992-1995. All were operated on by the same team of anesthetists and surgeons and
      all were transferred to the general ICU for at least the first 24 hours. 16 were
      above the age of 80 (Group I) and 84 below (Group II). We recorded preoperative
      factors (demographics, medical history, risk factor indices, EKG findings, as
      well as left ventricular ejection fraction (LVEF) and stress imaging when
      indicated); intraoperative factors (duration of surgery, size of aneurysm,
      complications and units of blood transfused); postoperative factors (length of
      ICU stay, duration of ventilation, APACHE II [Acute Physiological and Chronic
      Health Evaluation] and TISS [Therapeutic Intervention Scoring System] scores;
      complications in the ICU, need for readmission to the ICU, and mortality). In
      Group I LVEF was greater (p = 0.03) and aneurysm size significantly larger (p =
      0.036), but there were no other significant differences between the 2 groups with
      regard to pre- and intraoperative data. Group I patients were not ventilated as
      long (p = 0.038), but there were no significant differences in outcome factors.
      Mortality for the whole group was 5% and was not significantly different in the 2
      groups (1/16 in Group I and 4/84 in Group II). We conclude that there is no
      excess morbidity or mortality in octogenarians undergoing AAA surgery. However
      risk of the aneurysms rupturing is significantly greater since they are larger.
      We suggest that age not be considered the sole criterion for aneurysm repair, or
      at least not in selected patients with normal LVEF.

PMID- 10883180
TI  - [Acute myocardial infarction after honeybee sting].
AB  - Myocardial infarction due to honeybee sting is rare, and only a few authors have
      discussed the relationship between the sting, anaphylactic shock and myocardial
      infarction. We describe a case of acute myocardial infarction in a 44-year-old
      man after anaphylactic shock following honeybee sting. He did not have heart
      disease nor any known risk factors attributable to atherosclerotic coronary
      artery disease. He had almost normal coronary angiography with non-significant
      hemodynamic changes.

PMID- 10883181
TI  - [Carbamazepine hypersensitivity symptoms].
AB  - Carbamazepine (C) can cause a characteristic hypersensitivity reaction (CHS?.
      This multisystem reaction typically presents as fever, mucocutaneous eruption and
      lymphadenopathy. The syndrome usually develops between 1 week and 3 months after
      starting therapy, with involvement of the liver, lung, kidney and inappropriate
      secretion of ADH. The incidence is less than 0.001% in those treated with C and
      it is diagnosed clinically. With onset of CHS, the drug must be stopped and if
      there is no improvement, cortico-steroids should be started. When the diagnosis
      is in doubt, the patch test, lymphocyte transformation test, macrophage migration
      inhibitor factor, and other tests can be helpful. The pathogenesis is not known.
      Similar syndromes have been described with phenytoin and phenobarbital. There is
      clinical and in-vitro evidence of cross reactions between C and phenytoin. It is
      not known whether the CHS syndrome should be considered a premalignant state,
      with increased risk for the development of malignant lymphoma.

PMID- 10883182
TI  - [Alopecia due to Seroxat therapy].
AB  - There are 2 stages of alopecia, anagen and telogen effluvium, both of which may
      be associated with medication-related alopecia. We describe massive hair loss in
      a 51-year-old woman during treatment with Seroxat (paroxetine), which remitted
      after it was discontinued. Pathological mechanisms of drug-associated alopecia
      are complex and have yet to be fully elucidated.

PMID- 10883183
TI  - [Need for treatment of alcoholism in Israel and research on medical effects of
      alcohol at the beginning of the third millennium].

PMID- 10883184
TI  - [New findings in cystinuria].

PMID- 10883185
TI  - [Cardiovascular injury following electric shock].

PMID- 10883186
TI  - [Adolescents in Israel: health services planning].

PMID- 10883187
TI  - [Age-related macular degeneration: present situation and a glance toward the
      future].

PMID- 10883188
TI  - [Weight gain due to anti-psychotic medication].

PMID- 10883189
TI  - [Metastases to the female genital tract from extragenital cancers].

PMID- 10883190
TI  - [Arthrodesis of the shoulder--is there still a place for it in modern medicine?].

PMID- 10883191
TI  - [Oral clinical and laboratory findings in patients with gastrointestinal
      disorders].

PMID- 10883192
TI  - [Inflammatory bowel disease--infectious, environmental, genetic and immune
      mechanisms of pathogenesis].

PMID- 10883193
TI  - [Acute laryngeal trauma].

PMID- 10883194
TI  - [Marfan's syndrome].

PMID- 10883195
TI  - [The traditional materia medica in Jerusalem according to Titus Tobler].

PMID- 10883196
TI  - [Dr. Ya'akov Bergert (1883-1926)--the first Jewish physician killed in action in
      Israel].

PMID- 10883197
TI  - [Abraham Jacobi (1919-1930)].

PMID- 10883198
TI  - [The gift of breast feeding--the practice of breast feeding in Israel].
AB  - Breast milk is the optimal food for infant growth and development, the prevention
      of infectious diseases and mother-child bonding. From the economic perspective,
      breastfeeding is cost-effective both for the family and society as a whole. The
      Israeli Ministry of Health encourages breastfeeding as the exclusive source of
      nutrition for infants in the first 4-6 months of life, with gradual addition of
      complementary foods thereafter. The promotion of breastfeeding in Israel requires
      comprehensive national activity with involvement of all the stakeholders. This
      includes implementation of the International Code of Marketing of Breast Milk
      Substitutes and joining the international "Baby Friendly Hospitals" project.
      Knowledge of breastfeeding should be spread, health professionals should be
      encouraged to become agents of change, support by breast counselors should be
      encouraged, post-delivery vacations from work should be prolonged and empowerment
      of women implemented.

PMID- 10883199
TI  - [Etoposide and cisplatin for non-small cell lung cancer: trial at the Soroka
      Medical Center 1986-1994].
AB  - Etoposide and cisplatin (EP) has been the standard therapy for non-small cell
      lung cancer (NSCLC) at many cancer centers for over a decade. We analyzed our
      experience with EP in NSCLC to provide a baseline for comparison with new drugs.
      From 1986 through 1994, 46 of our patients with NSCLC received EP as first-line
      chemotherapy. Radiation therapy was administered to 25 of them, including 20 who
      received it immediately before or concomitantly with chemotherapy. Toxicity was
      mild and included only 1 episode of neutropenic fever and 1 case of reversible
      renal failure. Overall response was 22%. In 3, response was complete
      (pathologically documented in 2 of them) and in 7 partial. Median survival in
      locally advanced (stage III) and metastatic disease (stage IV and recurrent) were
      12 months and 7 months, respectively. 2 patients are alive and free of disease
      more than 6 years after diagnosis. Our results are consistent with other
      published studies of EP in NSCLC. EP provides modest benefit in locally advanced
      NSCLC, with minimal toxicity.

PMID- 10883201
TI  - [Differences in ethnicity and emergency department visits in the Negev].
AB  - The population of the Negev consists mainly of Jews and Bedouin, who have very
      different life styles. Patients of both ethnic groups use our emergency
      department exclusively, providing a unique opportunity to study comparative
      patient habits. In gathering and processing the information we used Data Mining
      technology, which allows search for unique patterns in large data bases. We
      examined demographic data on some 64,000 emergency department visits during 1997
      8, mostly medical and surgical cases, but not trauma cases. Many more were by
      Bedouin than Jews, and between the ages of 25 and 44, more by women than men.
      There were changes in trends in comparison with an arrival survey conducted some
      11 years before.

PMID- 10883200
TI  - [Placenta accreta with placenta previa after previous cesarean sections--a
      growing danger in modern obstetrics].
AB  - The increased rate of cesarean sections in recent decades has brought with it an
      increase in the frequency of placenta accreta. There are direct correlations
      between previous cesarean deliveries and also maternal age, with the risk of
      placenta accreta. There is also a direct correlation between placenta accreta and
      placenta previa. The risk of placenta accreta in women who have had placenta
      previa is 2% for those younger than 35 years and with no history of uterine
      surgery. The risk increases to 39% for those over 35 who have had 2 or more
      cesarean sections. We present 3 cases of placenta accreta admitted in 15 months,
      all of whom had a history of cesarean sections. The frequency of placenta accreta
      in our hospital is 1:1,579 deliveries, in line with the 1:1,420 in the
      literature. We consider hysterectomy the treatment of choice for this serious
      complication. When performing a cesarean in cases of placenta previa with a
      history of cesarean sections, the possibility of placenta accreta should be
      considered.

PMID- 10883202
TI  - [Preflight assessment by hypoxic inhalation test in cardiopulmonary patients].
AB  - Flying may expose passengers to hypoxic conditions, which may induce hypoxemia,
      particularly in those with chronic heart and/or lung disease. Onset of dyspnea,
      wheezing, chest pain, cyanosis and right heart failure can lead to urgent need
      for oxygen during flight. The hypoxia inhalation test (HIT) provides a safe and
      simple means of identifying those who may develop hypoxemia during flight. We
      report our experience with 48 self-reporting patients who underwent HIT prior to
      pre-planned air travel. They inhaled for 15-minute periods a reduced oxygen
      concentration (F1O2 15%) under normobaric conditions, during which O2 saturation
      was monitored by pulse oximeter; electrocardiogram, blood pressure and symptoms
      were also monitored. O2 saturation of < 85% (PaO2 50 mm Hg) was considered a
      positive test. In the 8 cases (17%) with a positive test, 5 had chronic
      obstructive pulmonary disease and 3 had cardiovascular and/or combined heart-lung
      disease. We calculated predicted O2 partial pressure in altitude (PaO2ALT) and
      compared it to actual results in the 8 patients with a positive HIT. In 5, use of
      the predicted formula would have under-diagnosed the hypoxemia that developed
      during the HIT. Thus, the results of the HIT changed treatment strategy in these
      patients. We recommend that patients with positive tests use O2 (2LPM or 4LPM)
      during flight. HIT is practical and of potential benefit in the objective
      assessment of patients with various degrees of heart, lung or combined heart-lung
      disease. Clinicians should be aware of the relative risk of hypoxia during flight
      in such patients, and of the value of HIT in identifying them, leading to
      increase in its use.

PMID- 10883204
TI  - [Tracheoesophageal puncture after total laryngectomy: follow-up of healing
      procedure].
AB  - Total laryngectomy due to malignant laryngeal tumors is followed by loss of
      speaking ability. Voice restoration in laryngectomized patients is the main
      target in their rehabilitation. Until the late 70's, esophageal speech was
      considered the most effective rehabilitation method. In 1980 Singer and Blom
      introduced a prosthesis for tracheoesophageal speech which has been gaining
      popularity. Tracheoesophageal puncture (TEP) can be performed either at the time
      of total laryngectomy, or later. 30 of our patients underwent TEP between 1991
      and 1999, 15 at the time of total laryngectomy and 15 as a delayed secondary
      procedure. Mean follow-up was 36 months (range 6 months to 8 years) during which
      all regained speaking ability. Over the long range, speech rehabilitation with
      the prosthesis was successful in 24 (80%). In only 1 in the primary TEP group did
      treatment fail, as the prosthesis had to be removed due to local recurrence of
      the tumor. Long range failure in 5/15 patients after secondary TEP stemmed from
      difficulties some patients had in handling the prosthesis and from psychological
      difficulties in adapting to the new speech device. Complications were mostly
      minor and occurred mainly in the secondary TEP group. TEP performed at the time
      of total laryngectomy, or later as a secondary procedure, is effective for speech
      rehabilitation after laryngectomy.

PMID- 10883203
TI  - [Epstein-Barr virus infections in adults: a diagnostic challenge].
AB  - The adult form of mononucleosis caused by Ebstein-Barr virus (EBV) is different
      from the disease in children and adolescents. In most adults there is no
      pharyngitis or lymphadenopathy, fever is much more prolonged, abnormal liver
      function is frequent and lymphocytosis and the presence of atypical lymphocytes
      are not common. Such an atypical disease presentation often results in delayed
      diagnosis and unnecessary treatments. We describe 2 adults with such atypical
      presentations and complications of EBV infection.

PMID- 10883205
TI  - [Laparoscopic surgery in treating hepatic cysts].
AB  - Solitary and multiple hepatic cysts are now more commonly found because of
      advances in imaging techniques. Most hepatic cysts are asymptomatic, but when
      they do cause symptoms they require surgical intervention. The advent of
      laparoscopy and of laparoscopic ultrasonography allow comprehensive evaluation
      and treatment of the cysts. 12 patients with hepatic cysts were treated
      laparoscopically. 8 with single cysts underwent successful subtotal cyst
      resection without signs of recurrence (up to 20 years of follow-up). 4 with
      polycystic liver disease underwent sub-total resection of superficial cysts. Deep
      cysts were unroofed and drained under laparoscopic ultrasound guidance. In this
      group, 1 experienced recurrence of symptoms and required partial hepatectomy of
      the involved segment. In another, a connection between a deep cyst and bile ducts
      was demonstrated and cystojejunostomy was performed. The laparoscopic approach in
      the management of patients with liver cysts is effective and safe, and we
      recommend it as the procedure of choice for single hepatic cysts. In polycystic
      liver disease the procedure is much less successful.

PMID- 10883206
TI  - [Acipimox (Olbetam) as a secondary hypolipemic agent in combined
      hypertriglyceridemia and hyperlipidemia].
AB  - 32 patients with hypertriglyceridemia, excessive hypertriglyceridemia, and
      combined hyperlipidemia, were treated with the nicotinic acid derivative acipimox
      (Olbetam). First line treatment with bezafibrate, or statins in some with
      combined hyperlipidemia, had failed. In 10 acipimox was discontinued due to side
      effects or absence of clinical response. The other 22 completed 6 months of
      treatment with no side effects. Acipimox caused a significant 54% decrease in
      triglyceride levels, a 23% decrease in total cholesterol, and a 12% increase in
      HDL-cholesterol. LDL-cholesterol was difficult to calculate because of the high
      triglyceride levels, so no results are presented. Although acipimox was much
      better tolerated than nicotinic acid, it also had side effects, but fewer.
      Acipimox can therefore be used as a second-line drug, mainly in those with
      combined hyperlipidemia and hypertriglyceridemia.

PMID- 10883207
TI  - [Acetaminophen toxicity in children as a "therapeutic misadventure"].
AB  - Acetaminophen toxicity after repeated administration of amounts that only
      moderately exceed recommended doses, is being increasingly reported in alcoholic
      or fasting adults. Pediatric experience with this pattern of acetaminophen
      toxicity is sparse. We present 2 children who developed severe hepatic damage,
      with renal insufficiency as well in 1, after 15-20 mg/kg of acetaminophen, given
      at 4-hour intervals for 3-4 days during an intercurrent febrile illness. When
      given in doses as low as 20 mg/kg at frequent intervals for a number of days, the
      drug puts children who are vomiting or have sharply reduced caloric intakes at
      increased risk for severe toxicity. Increased caution and awareness of the toxic
      effects of acetaminophen are needed, and it should be dispensed with appropriate
      package-label warnings.

PMID- 10883209
TI  - [The "hunt" for the genes responsible for schizophrenia and bipolar disorder].

PMID- 10883208
TI  - [Learning life saving skills on newly deceased].

PMID- 10883210
TI  - [Idiopathic postural orthostatic tachycardia: current concepts of etiology,
      diagnosis and management].

PMID- 10883211
TI  - [Prophylaxis after occupational exposure to HIV].

PMID- 10883212
TI  - [School health, a window of opportunity for the improvement of health and well
      being of children and adolescents in Israel].

PMID- 10883213
TI  - [Suggested guidelines for the use of opioid drugs in pain of non-malignant
      origin].

PMID- 10883214
TI  - [Evaluation of the accuracy of automatic blood pressure measuring devices].

PMID- 10883215
TI  - [Diabetes and hyperparathyroidism--a new connection between old diseases].

PMID- 10883216
TI  - [Psoriasis as an immunological disease: pathogenic and therapeutic aspects].

PMID- 10883217
TI  - [Bikur-Holim Hospital and Dr Puffeles: health care of the Jewish population of
      Jerusalem at the end of the 19th Century].

PMID- 10883218
TI  - [Albert B Sabin (1906-1993)].

PMID- 10883219
TI  - [Professor Lonnrot, Dr Crawford, Dr. Tchernichowski and the Kalevela].

PMID- 10883220
TI  - [16th World Congress on Asthma, Buenos Aires, Argentina, October 17-20, 1999].

PMID- 10883221
TI  - [Prediction of physiological response from mathematical models].
AB  - The ability to predict the physiological responses of workers exposed to extreme
      environmental conditions, has been a challenge to environmental physiologists for
      more than 3 decades. Therefore, mathematical models have been developed to
      predict metabolic rate under various levels of work intensity and dynamic changes
      in body temperature and heart rate. Based on the effect of exercise on the
      cardiovascular system, a model was developed to predict mean arterial blood
      pressure as a function of heart rate. Physiological strain could also be
      estimated on the basis of thermoregulatory and cardiovascular strains. This paper
      summarizes knowledge accumulated during 25 years of studies in the field of
      mathematical modeling of physiological parameters. Besides analyzing the logic
      underlying each model, it explains the scientific approach in developing a model
      from its early concept to the model's application in the field.

PMID- 10883222
TI  - [Pre-induction sport activity in prevention of stress fractures in elite infantry
      recruits].
AB  - Pre-induction sports participation of 392 elite infantry recruits was evaluated
      for correlation with incidence of stress fractures (SF) during 14 weeks of basic
      training. 23.7% developed lower extremity stress fractures. 72% of the recruits
      had participated in sports on a regular basis during the 2 years prior to
      induction. Their fitness as examined by the Bar-Or induction fitness test, was
      significantly better than that of those who had not trained. 14.9% of the
      soldiers who had previously participated in ball games (primarily basketball) as
      an only sport suffered stress fractures, compared to 31.0% of those whose only
      sport was running (p < 0.005). Training for only 6 months prior to induction had
      no effect on the incidence of SF. The reason for the difference between ball
      games and running is probably related to the higher strains and strain rates
      developed during ball games and to their multidirectional nature, as compared to
      running. These findings suggest that participation in a pre-induction program
      that includes activities that create strains, such as basketball, can reduce
      incidence of SF in infantry recruits. The training period has to last at least 2
      years.

PMID- 10883223
TI  - [Man in a hot climate--early studies of the Institute of Military Physiology].
AB  - In the 1950's many IDF soldiers were hospitalized for heat stroke--about 25% of
      whom died. Analyzing these cases revealed that commanders misinterpreted human
      ability to perform in the heat and ignored basic concepts of fluid and
      electrolyte balance and heat load. In the early 1960's a series of studies was
      conducted with regard to soldiers' performance in the heat. The first study
      (1959), which later became a classic, was conducted during a 21-day march from
      Eilat to Metula, crossing all climatic zones of Israel. The study was followed by
      other investigations which approached the issues of voluntary dehydration, fluid
      consumption vs sweat loss, salt additives, and the effect of heat load on
      performance. Based on these early studies, proper regulations were issued to
      field officers. Over the years, the lessons learned from these studies saved many
      lives. The number of cases of heat stroke and of other climate-related injuries
      was dramatically reduced, and performance was enhanced.

PMID- 10883224
TI  - [Military psychiatry in Israel: a 50-year perspective].
AB  - The history of military psychiatry in Israel may be divided into 2 main periods.
      The first extended from the War of Independence in 1948, through the Sinai, Six
      Day and Yom Kippur Wars. Its outstanding feature was avoidance of the issue of
      combat stress reaction (CSR). The Yom Kippur War made the recognition of CSR
      inescapable, assisted in breaking up denial, and served as a stimulus for
      development of the next phase of the system. This second phase was characterized
      by impressive progress in all areas of military psychiatry. The rich experience
      accumulated during the wars, together with the assimilation of a research culture
      which began blooming, especially in the wake of the Lebanon War, aided the
      development and crystallization of concepts related to combat and non-combat
      military psychiatry alike. The build-up of the mental health organization
      overlapped field deployment of the Medical Corps.

PMID- 10883225
TI  - [New psychopharmacological approaches in mental health as applied by the Israel
      Defense Forces].
AB  - In the past decade there have been far-reaching developments in
      psychopharmacology. Previously, only a few classes of medication were at the
      disposal of psychiatrists, as many had serious side effects that limited their
      use. Now our psychopharmacological armamentarium has grown considerably, allowing
      for greater choice of treatment in the military. We review these developments,
      and discuss the special considerations to be taken into account when treating
      soldiers with psychiatric medication. We discuss suitable medication for ongoing
      outpatient treatment, as well as the standard list of medication currently used
      by units deployed in the field. Advances in psychopharmacologic treatment should
      enable more soldiers to serve safely in the military with fewer restrictions on
      their duties.

PMID- 10883226
TI  - [Burn injuries to military personnel during the Six Day War].
AB  - About 2500 soldiers were injured during the Six Day War (June 1967) of whom 115
      suffered from burns. In 34 of them 15% or more of their body surface was involved
      and 11 died. Typical features of these burn cases were supplementary injuries, a
      high rate of infection, and long periods of hospitalization. Prophylactic
      antibiotics were not useful. The general condition of many deteriorated during
      the first week after injury, indicating the importance of treating severe burns
      in specialized facilities.

PMID- 10883227
TI  - [Medical support during the Sinai War of Attrition (1968-1970) from a 30-year
      perspective].
AB  - The War of Attrition between Israel and Egypt along the Suez Canal line lasted 23
      months (9/1968-8/1970), during which the Israel Defense Forces (IDF) were mostly
      in fixed fortifications. A few of the important principles of field medical
      support, which became cornerstones of IDF procedure, were established during that
      war. These included use of armored vehicles for evacuation under artillery fire,
      as well as emergency treatment, physiological stabilization, and maintenance of
      the wounded until evacuation. The latter objectives were achieved by stationing
      medical officers and paramedics within the fortifications, where they remained
      with the troops. A field surgical hospital was established in Refidim which had a
      trained surgical staff and a well-equipped emergency department. It included an
      operating theater and post-op recovery facilities for proper surgical care until
      evacuation to hospitals in the rear. Tables showing the number of casualties
      throughout 1 year of the War of Attrition are presented. Better personal
      shielding by helmets and body shields decreased the number and severity of head
      and thoraco-abdominal injuries. The relative large number of those who died-of
      wounds was due to the proximity of medical facilities, so that treatment could be
      administered within the fortifications. Otherwise, many more would have been
      included among the killed-in-action.

PMID- 10883228
TI  - [Israel Naval Medical Institute: 20 years of applied research, and future goals].
AB  - The Israel Naval Medical Institute (INMI) is unique as a research center located
      in a naval base and having close inter-relations with naval underwater units. It
      is ideal for applied research, and for mutual exchange of needs and of ideas and
      instructions. Factors making this institute so suitable for applied research
      include: direct personal communication with combat divers, professional naval
      divers, submariners, civilian recreational divers and professional civilian
      divers, as well as naval vessel crews prone to seasickness; hyperbaric oxygen
      therapy is administered in cooperation with a large neighboring hospital. Close
      spatial and personal relations with an academic institution (the Technion, with
      its Faculties of Medicine, Biology and Biophysics) provide a basis for
      cooperative research which expands research capabilities, and allows access to
      extensive expertise, instrumentation and equipment. Close ties with physicians
      who served at the INMI in the past also bring them into this research community.
      During their specialization, physicians may spend up to 6 months working with us
      on a research project. Undergraduate, graduate and post-graduate students may
      complete their research at our institute with the agreement of their parent
      academic institutions. Much of the research can be released to the international
      community. However, some is classified, serves only internal needs or is not of
      public interest. The number of published papers has stabilized since 1991 at
      about 16 a year. Studies of gas exchange and oxygen toxicity originate mainly in
      the Hyperbaric Research Unit, research on motion sickness in the Motion Sickness
      and Human Performance Laboratory, and work on hyperbaric and diving medicine in
      the Clinical Section of the INMI.

PMID- 10883229
TI  - [Decompression sickness in divers treated at the Israel Naval Medical Institute
      between the years 1992 to 1997].
AB  - Clinical characteristics of 125 divers treated for decompression sickness (DCS)
      in the hyperbaric multiplace chambers of this Institute during 1992-1997 were
      analyzed retrospectively. In 62 (51%) the diagnosis was DCS Type I (joint pain or
      skin involvement) and in 60 (49%) DCS Type II (neurological, inner ear or
      pulmonary disease). Risk factors for the evolution of DCS were depth and duration
      of the dives involving accidents, violation of recommendations of the
      decompression tables, and repeated dives. Results were available for 112 of the
      125 patients. 54 of them (48%) recovered completely, and another 54 recovered
      partially; 4 did not respond to treatment. Inner ear DCS was less responsive to
      hyperbaric oxygen treatment (p = 0.0001). There was significant improvement of
      neurological function in those with severe neurological injury (p = 0.0001).
      Rapid diagnosis and transportation of divers with DCS to a hyperbaric chamber is
      of crucial importance.

PMID- 10883230
TI  - [Trends in epidemiology of hepatitis in the Israel Defense Forces-- direction
      over several years].
AB  - During the 50's and 60's there were large scale epidemics of hepatitis A every 3
      4 years in the Israel Defense Forces. During these epidemics the annual incidence
      exceeded 10/1000 soldiers at risk. There has been a highly significant decrease
      in rates during the past 30 years. The average annual incidence of clinically
      identified viral hepatitis A decreased from an average of 6/1000 during the 60's
      to 2.5/1000 during the 70's. The decrease coincided with the introduction in the
      1970's of wide-scale post-exposure prophylaxis with immune serum globulin (ISG).
      The incidence was further significantly reduced to 0.5-1.0/1000 with the
      introduction of pre-exposure prophylaxis with ISG, starting in 1978 (p < 0.001).
      Other factors probably played a role in accelerating the decline in morbidity,
      such as improvement in personal hygiene and sanitation facilities, and in waste
      disposal and other aspects of military environmental health. These improvements
      were probably more pronounced in the civilian sector, leading to decreased
      exposure of children to the virus and consequently a higher proportion of
      seronegatives at induction. Increase in the proportion of recruits without
      natural immunity to the virus poses greater risk, both in terms of personal
      morbidity as well as military operational ability. This risk, combined with
      problems of ISG use and availability, has propelled hepatitis A prevention policy
      towards the use of the new inactivated vaccines.

PMID- 10883231
TI  - [Development of molecular tests for rapid detection of enteropathogens].
AB  - Amplification of specific DNA sequences by polymerase chain reaction (PCR),
      enables rapid, sensitive and direct, specific identification of pathogens at very
      low concentrations in clinical samples. Studies in recent years have reported
      identification of several enteropathogens directly from stool samples by PCR. The
      amplification process includes the use of primers complementary to the DNA
      sequences specific to the pathogen, thus relying on the pathogen's genotype,
      rather than its phenotype on which identification by the methods of classical
      microbiology were based. We have developed PCR protocols for the differential
      identification of enteropathogens resembling the normal flora (enterotoxigenic E.
      coli (ETEC), E. coli O-157), Shigella spp, and the detection of enteropathogens
      that can not be grown on classic growth media (Norwalk virus). The amplification
      process is inhibited by several substrates present in fecal material (phenol,
      hemoglobin), limiting DNA extraction by phenol. The protocols we have developed
      for direct detection of Shigella spp and ETEC in stools circumvent inhibition of
      PCR by the use of a 4-hour pre-enrichment step in brain-heart infusion broth.
      Rapid and accurate identification of enteropathogens is important for prompt and
      focused intervention to stop the chain of transmission in outbreaks of
      gastroenteritis in military and civilian populations.

PMID- 10883232
TI  - [Human experimentation in the Israel Defence Forces--between the hammer of
      necessity and the anvil of ethics].

PMID- 10883233
TI  - [Fifty years of airborne medicine in Israel].

PMID- 10883234
TI  - [Israeli Defence Forces registry of trauma injury data].

PMID- 10883235
TI  - ["From strength came forth sweetness"--on the contribution of military conflicts
      to the development of burn care in Israel].

PMID- 10883236
TI  - [External heat stroke--is it preventable in military settings?].

PMID- 10883237
TI  - [Evolution of management of penetrating brain wounds--lessons learned from wars
      since Israel's independence].

PMID- 10883238
TI  - [Stress fractures--contribution of the Israel Defense Forces to understanding
      their mechanisms, their prevention and treatment].

PMID- 10883239
TI  - [Anthrax].

PMID- 10883240
TI  - [Jet lag causing or exacerbating psychiatric disorders].
AB  - Desynchronization of circadian rhythmicity resulting from rapid travel through at
      least 4 time zones leads to symptoms of jet lag syndrome. The most commonly
      experienced symptoms in normal individuals are sleep disorders, difficulties with
      concentrating, irritability, mild depression, fatigue, and gastrointestinal
      disturbances. There is strong evidence relating affective disorders to circadian
      rhythm abnormalities, such as occur in jet lag. Less convincing suggestions
      relate jet lag to psychosis. We presume, relying on the literature and our
      accumulated experience, that in predisposed individuals jet lag may play a role
      in triggering exacerbation of, or de novo affective disorders, as well as, though
      less convincing, schizophreniform psychosis or even schizophrenia. An
      illustrative case vignette exemplifies the possible relationship between jet lag
      following eastbound flight and psychotic manifestations.

PMID- 10883241
TI  - [Color Doppler imaging of central retinal artery in retinopathy of prematurity].
AB  - Color Doppler imaging (CDI) is a noninvasive technique, combining 2-dimensional
      brightness-modulated (B-mode) ultrasound evaluation of eye and orbital
      structures, with simultaneous color-coded Doppler imaging of orbital blood flow.
      It has been used to characterize various ophthalmic disorders in adults.
      Currently there is no data describing orbital blood flow parameters in either
      normal children or in those with ophthalmic disease, such as the retinopathy of
      prematurity (ROP). We evaluated blood flow in the central retinal artery of
      preterm infants undergoing examination for ROP. We also investigated whether
      useful readings could be obtained on a consistent basis, and the reproducibility
      of differences in central retinal artery blood flow between subjects with and
      without ROP (including the influence of "plus" disease). We obtained hemodynamic
      readings in 43 of 46 eyes of preterm infants. 13 eyes had no signs of ROP; 18 had
      ROP (at least stage 1) without "plus" disease, and 12 had ROP with "plus"
      disease. There were no statistically significant differences in systolic blood
      flow velocity within the 3 groups. However the average velocity was slower in the
      "plus" disease group, correlating with the clinical finding of dilated and
      tortuous blood vessels which characterize the posterior retina of ROP eyes with
      "plus" disease.

PMID- 10883242
TI  - [Use of civilian emergency departments by the Israel Defense Force for emergency
      care for soldiers].
AB  - Many physicians, civilian as well as in military, feel that some referrals of
      soldiers to civilian emergency departments are inappropriate and that soldiers
      should receive medical attention within their military units. We therefore
      evaluated referrals of soldiers to our emergency department. 707 referral letters
      from military physicians and the corresponding emergency room discharge letters
      were evaluated. Most soldiers were referred for mild trauma (45.0%) or
      miscellaneous diseases (52.9%); 22 (3.1%) were hospitalized. It appears that some
      military physicians use the civilian hospital emergency department as a surrogate
      for an outpatient specialty clinic and for x-ray and laboratory services. This is
      in contrast to the designated functions of the emergency department which are to
      provide emergency and trauma services and to evaluate the need for
      hospitalization of referred patients.

PMID- 10883243
TI  - [FK506 (tacrolimus) does not increase hepatic damage due to hypoperfusion].
AB  - Deterioration of hepatic function following liver transplantation is a known
      complication, sometimes attributed to the use of cyclosporin A. Reaction to
      tacrolimus (Prograf), a relatively new and effective immunosuppressant drug, is
      thought to result in a much lower grade of organ dysfunction, especially in the
      transplanted liver. Using the ex-vivo rat model of isolated perfused liver, we
      evaluated hepatocellular damage and oxygen extraction when tacrolimus was
      administered following liver hypoperfusion. Tacrolimus did not worsen hepatic
      dysfunction caused by the hypoperfusion. Therefore using tacrolimus in the
      perioperative period might be safer than cyclosporin A, which tends to worsen
      hepatic damage in the presence of hypoperfusion.

PMID- 10883244
TI  - [Mitral valve repair in ischemic cardiomyopathy with severe left ventricular
      dysfunction].
AB  - Patients with ischemic mitral insufficiency and poor left ventricular function
      are high operative risks. We present 101 patients who had mitral valve repair in
      our department: 21 had severely reduced left ventricular function, 19 were in
      NYHA functional Class IV, and 2 in Class III. All had concomitant coronary artery
      bypass. There was no early operative mortality, but there were 2 late deaths
      (9.6%). At follow-up (3-36 months) all valves were functioning normally, 9
      patients (43%) were in NYHA functional Class I, and 4 (19%) in Class II. Our
      experience shows that repair of ischemic mitral insufficiency in the presence of
      severe left ventricular dysfunction can be performed with good results, and is
      preferable to mitral valve replacement. Late follow-up showed significant
      symptomatic improvement.

PMID- 10883245
TI  - [Breast cancer after mantle field irradiation for Hodgkin's disease].
AB  - Effective use of modern therapeutic modalities results in the cure of 75%-80% of
      Hodgkin's disease patients, regardless of stage. The major threat to continued
      survival is, therefore, not recurrent disease but development of second
      malignancies. Recent reports have firmly established the increased risk of breast
      cancer developing in women treated with mantle field irradiation. We describe 3
      women who developed breast carcinoma following mantle field irradiation for
      Hodgkin's disease. Their clinical course was consistent with that reported in
      larger series. They were relatively young when irradiated and there was a long
      interval between radiation therapy and the diagnosis of breast cancer. Review of
      the literature shows that there may be a role for prophylactic mastectomy after
      irradiation for Hodgkin's disease.

PMID- 10883246
TI  - [Concomitant surgery--coronary artery bypass and pulmonary lobectomy].
AB  - Coronary artery disease amenable to percutaneous interventions or coronary artery
      bypass grafting, and resectable lung cancer are major causes of morbidity and
      mortality. We present our experience in the treatment of 3 patients (men aged 64
      and 66 and a woman of 77) who each had significant coronary artery disease and a
      resectable lung tumor. They underwent combined coronary artery bypass grafting
      and pulmonary lobectomy. We conclude from our experience and review of the
      literature that concomitant surgery in such cases is safe and effective,
      decreases suffering, and decreases the cost of 2 separate invasive procedures.

PMID- 10883247
TI  - [Israel hospital pharmaceutical services: a national survey].
AB  - Results of a 1996 survey of hospital pharmaceutical services in Israel are
      presented. A questionnaire was mailed to 46 pharmacy directors in Israel
      hospitals of which a total of 33 were returned (72%). The main services provided
      at hospital pharmacies are production of pharmaceuticals and inventory
      management. The pharmacy directors estimated that more then half of their
      pharmacists' time was spent on technical work that did not need their academic,
      professional knowledge. In Israel general hospitals there are on the average 1.23
      full time pharmacist positions per 100 hospital beds and 1.09 positions for other
      pharmacy employees. A similar survey carried out in the United States showed an
      average of 7.4 pharmacists per 100 hospital beds. Pharmacists there have broad
      clinical roles which, in general Israeli pharmacists do not have. Computer
      systems are used in our pharmacies mainly for inventory management. About half of
      the directors did not think that the location, structure and furnishings of their
      pharmacy were appropriate for its role. Under current conditions, Israel hospital
      pharmacies are not organized to provide pharmaceutical services beyond inventory
      management and pharmaceutical production. Appropriate budgets and personnel are
      required to develop clinical pharmacy services at Israel hospitals. This would
      lead to improved quality of drug treatment and cost-containment and would allow
      pharmacists to exploit their knowledge, skills and training that under the
      current system, are only partially utilized.

PMID- 10883248
TI  - [Thallium scan and pulmonary carcinoma].
AB  - A 70-year-old man was admitted for exacerbation of congestive heart failure. In
      his assessment thallium scan of the heart was performed. An incidental finding
      was a focus of absorption in the right lung. The lesion was later diagnosed as
      adenocarcinoma based on the cytological findings.

PMID- 10883249
TI  - [Prader-Willi syndrome: medical, emotional and cognitive facets].
AB  - Prader-Willi syndrome, first described in 1956, is characterized by marked
      hypotonia, hyperphagia, severe obesity, short stature, hypogonadism, orthopedic
      problems, breathing-related sleep disorders, mild to moderate mental retardation
      and behavioral abnormalities. The incidence of this syndrome, an expression of a
      genetic imprinting error in chromosome 15, is 1:10,000-1:25,000. We describe the
      medical, emotional and cognitive parameters of 34 patients in our
      multidisciplinary clinic for Prader-Willi syndrome. Their ages range from 5
      months to 40 years and 20 are males. Excessive weight gain started at the age of
      6 years, increasing to 170-370% of that predicted by height and age and short
      stature started after the age of 12. All males have hypogonadism; 6 patients have
      scoliosis. Breathing-related sleep disorders have occurred in 15. Children above
      the age of 8 years underwent neuropsychological assessment: half (9/18) have
      borderline intelligence while a quarter have low-normal intelligence and the
      remainder mild to moderate mental retardation. Behavioral and social problems are
      common, and become more prominent during adolescence. ADHD was diagnosed in
      10/18.

PMID- 10883250
TI  - [Whole bowel irrigation in infants for acute iron poisoning].
AB  - Acute iron poisoning is a major cause of death due to poisoning in children, so
      knowledge of its presentation and appropriate management are necessary. Whole
      bowel irrigation, used routinely in preparation for elective surgery and
      colonoscopy, are safe and effective procedures. In recent years whole bowel
      irrigation has been used several times in various toxic situations, including
      acute iron poisoning. We report our successful experience treating acute iron
      poisoning in a 1-year-old girl using whole bowel irrigation and deferoxamine. The
      safety and theoretical effectiveness of the procedure, although not proven in
      controlled clinical studies, suggests the use of whole bowel irrigation as
      treatment for acute iron poisoning.

PMID- 10883251
TI  - [Scaphoid fractures in children].
AB  - The scaphoid is the most common carpal bone fractured in adults. In children the
      fracture is distinctly uncommon. We present our experience with 23 children
      treated between 1987-1998, 19 of them with fractures in the distal third of the
      wrist; there were 11 avulsions, 4 waist fractures, and 12 were undisplaced. The
      mechanism of injury was a direct blow or a fall onto the outstretched hand.
      Immobilization in a plaster cast led to union in all except 1 case. Based on our
      experience and study of the literature, it is evident that scaphoid fractures,
      although uncommon, do occur. Thorough clinical and radiological examination of
      children with a forearm or wrist injury is important in detecting such fractures.

PMID- 10883252
TI  - [Smoking while using oral contraceptives: a risky pleasure].

PMID- 10883253
TI  - [The diagnostic approach in patients with hemoptysis].

PMID- 10883254
TI  - [Measurement of the percentage of body fat in children and adolescents and its
      connection with physical physical training].

PMID- 10883255
TI  - [Acquired hemophilia].

PMID- 10883256
TI  - [Molecular mechanisms underlying post-traumatic stress disorders].

PMID- 10883257
TI  - [Pregnancy in the patient with essential thrombocythemia].

PMID- 10883258
TI  - [Infections and coronary artery disease].

PMID- 10883259
TI  - [Guidelines for evaluation and treatment of erectile dysfunction].

PMID- 10883260
TI  - [Topiramate--a new antiepileptic drug for children].

PMID- 10883261
TI  - [Israel must change its support policy in medical research--from neglect to
      development].

PMID- 10883262
TI  - [Medicine during the Holocaust as reflected in the medical literature of the
      nineties].

PMID- 10883263
TI  - [Medical dilemmas in the shadow of ghetto life according to the play "In the
      Cellar" by Y Sobol].

PMID- 10883264
TI  - [Bela Schick (1877-1967)].

PMID- 10883265
TI  - [Molecular biology and gene engineering of phytase].
AB  - Phytase is a new-style enzyme used in monogastric animal feed. The addition of
      phytase to feed can increase phosphorus availability, decrease environmental
      phosphorus pollution and improve the performance of animal. This paper reviews
      the research progress and trend in recent studies related to molecular biology
      and gene engineering of phytase.

PMID- 10883266
TI  - [Cloning and expression of human Cu/Zn superoxide dismutase gene in Lactococcus
      lactis].
AB  - The cDNA encoding human Cu/Zn SOD was amplified by RT-PCR using the total RNA of
      human liver as the template, and was cloned into an E. coli expression vector
      pET23b. After the DNA sequence was determined, the recombinant plasmid pET23bsod
      was introduced into E. coli BL21(DE3)/pLysS. SDS-PAGE analysis revealed that the
      recombinant E. coli expressed the predicted 19 kDa human Cu/Zn SOD, and its
      amount was over 50% of total proteins. The Cu/Zn SOD cDNA was then subcloned into
      a lactococcal expression vector pMG36e, and resulting pMG36esod was introduced
      into L. lactis MG1363 by electroporation. The human Cu/Zn-SOD was expressed up to
      5% of the soluble proteins, and the enzymatic activity was also observed by SOD
      activity dying.

PMID- 10883267
TI  - [The diploid of genetically engineered yeast for expression of hybrid HBsAg gene
      SA-28].
AB  - By mating a yeast haploid expressing hybrid HBsAg gene SA-28, Y19/YFD158, with
      another hapolid Y95, the diploid Y95xY19/YFD158 was constructed. The experiments
      showed that the cell density of the diploid in fermentation was three time higher
      than that of the haploid, the stability of expression vector in the diploid was
      much higher than in the haploid, the xpression level of hybrid HBsAg gene of the
      diploid was more than three time higher than that of the haploid and the average
      cope number in diploid cell was a little lower than that in the haploid.

PMID- 10883268
TI  - [Immunization of mice with plasmid DNA against malaria and regulation of antigen
      expression by tetracycline-controlled promoter].
AB  - Sequence of MSP1-31 of Plasmodium falciparum was constructed into eukaryotic
      expression vector pTRE, which could be repressed by tetracycline (Tc) and
      resulted in recombinant plasmid pTRE-31. The plasmid was injected into the
      quadriceps muscle of BALB/c mice with Tc responsive plasmid pTet-off to measure
      specific antibodies. The MSP1-31 prokaryotic expressed protein was used as
      antigen in ELISA. Results showed that mice orally administered by Tc had a
      seroconversion rate of 7.1% (1/14) 4 weeks after injection, whereas the control
      mice had a seroconversion rate of 100% and the titers of antibody were raised
      continusly within 12 weeks. The study suggested that the recombinant plasmids
      pTRE-31/pTet-off could efficiently induce humoral response against MSP1-31 of
      malaria. Moreover this immune response was controlled by Tc and was reversible
      after withdrawal of Tc dilivery. The induction of antibody by removing Tc at the
      fourth week after injection indicated that DNA vaccine could remain in mice and
      capable of expressing antigen for at least 4 weeks.

PMID- 10883269
TI  - [Improved protoplast-derived plants of Astragalus adsurgens through somatic
      embryogenesis].
AB  - Embryogenic callus was obtained only from hypocotyl explants of Astragalus
      adsurgens and light inhibited the formation of embryogenic callus. A high yield
      (1.2 x 10(6)/g F. Wt.) of protoplasts with high viability (over 80%) could be
      isolated from 10-day-old embryogenic callus. Protoplasts were induced to undergo
      sustained division and to form cell colonies when cultured in agarose-solidified
      medium (KMP) containing 1/4 strength of mineral salts and supplemented with 1.5
      mg/L 2, 4-D, 0.5 mg/L BA and 0.5 mol/L glucose at a plating density of 1.0 x
      10(5)mL, where the plating efficinency was 16.8%. Conditioning medium
      significantly improved the formation of cell colonies. When protoplast-derived
      colonies were maintained at 4 degrees C for 2 weeks and subsequently transferred
      onto medium (MS) with 0.1 mg/L NAA and 1.0 mg/L BA, somatic embryogenesis
      occurred. Frequency of cell colonies producing somatic embryos reached 70%, and
      the number of somatic embryos per gram cells was over 200. Cultured on hormone
      free half-strength MS medium, somatic embryos developed into healthy plantlets
      with normal chromosome complement.

PMID- 10883270
TI  - [The influence on oxgen-carrying capacity of procine hemoglobin while attached
      PEG to increase its total molecular weight].
AB  - Increasing the total molecular weight of hemoglobin through PEG modification has
      been proved to be a better choice in prolonging vascular retention time. As a
      long, linear, hydrophilic molecular, PEG exerts significant influence on the
      oxygen-carrying properties of porcine hemoglobin (pHb) when attached. PEG
      hemoglobins exhibit a wide range of differences in their properties depending on
      which molecular weight PEG is selected, how many PEGs are bound and whether the
      allosteric cofactors exist or not. Furthermore, DBBF intracross-linked pHbs are
      bound to various active PEG. As a result, with the combination of the three
      methods: DBBF intracross-linking, allosteric cofactors involving and PEG
      conjugating, a tetramer stable and high oxygen-carrying capacity pHb derivitive
      with large molecular weight is obtained.

PMID- 10883271
TI  - [Functional and structural analysis of a prokaryotic enhancer-like element in
      Escherichia coli MC1061 strain].
AB  - Cat and lacZ genes were used as reporter gene and three prokaryotic enhancer-like
      element (MC2, MC8 and MC9) were identified in the genomic DNA of MC1061 strain.
      All three fragments can improve the expression of lacZ gene by 2-5 times with the
      orientation independence. The results of in vivo transcription and Dot blot
      hybridization assays suggested that MC8 regulated the expression of lacZ at
      transcription level. Stepwise deletion expreriments showed the functional domain
      of MC8 located at 450-950 bp, and in regions 450-600 bp and 840-950 bp contain at
      least one functional loci. Sequence data indicated three are 3 A + T rich
      sections in MC8, 2 of them are in the functional loci.

PMID- 10883272
TI  - [Selection of high avermectins producing strain and identification of avermectin
      B1].
AB  - Three types of colony, powdery gray, white and bald, were isolated from
      Streptomyces avermitilis ATCC31272. Among them, only the powdery grey one
      produces avermectins. Sa-76 strain was selected from the powdery grey strain by
      mutation with high energy electric flow, and its avermectins titer attainde 100
      micrograms/mL in shaking flask. Avermectin B1 was extracted and purified from the
      mycelia of Sa-76, and identified by UV, IR, 1H-NMR, 13C-NMR and mass spectra.
      After Sa-76 strain was treated twice with NTG, a strain named Sa-76-8 was
      selected with avermectins titer over 2000 micrograms/mL. The Sa-76-8 strain was
      treated with NTG once again, and a high avermectins producing strain named as Sa
      76-9 with avermectins titer up to 3500-4000 micrograms/mL was selected.

PMID- 10883273
TI  - [Computer modeling and experimental research of interactions between two anti
      hTNF alpha monoclonal antibody variable regions and hTNF alpha].
AB  - On SGI workstation, we constructed two anti-hTNF alpha McAbs by means of
      homologous protein-structure-prediction method. And then, on the basis of
      relative experimental results and the surface properties of hTNF alpha and two
      McAbs, we performed the docking of hTNF alpha into two anti-hTNF alpha McAbs. In
      order to confirm the models, we prepared two hTNF alpha mutants designed
      according to the binding models, analysed and predicted the possible changes in
      complexes resulted from hTNF alpha mutations. The experimental analysis results
      proved these complex models. This will make the base of our next antibody
      humanization and/or reshape work.

PMID- 10883274
TI  - [Cloning and expression of the detoxifying gene in cyanobacteria].
AB  - Plasmid pRL-B1 was constructed from detoxifying gene(called B1) of pesticide
      resistant Culex and from plasmid pRL-439 containing the strong promoter PpsbA. E.
      coli-cyanobacteria shuttle expression plasmid pDC-B1 was constructed from shuttle
      vector pDC-8 and from recombinant plasmid pRL-B1, then it was transferred into
      Synechococcus sp. PCC7942 by triparental conjugative transfer. The existence of
      B1 was detected by Southern analysis, and the expression of B1 was confirmed by
      enzyme activity analysis of detoxification of transgenic cyanobacteria.
      Experimental results indicated that the transgenic cyanobacteria could degrade
      beta-naphthyl acetate(beta-NA), a specific substrate of esterase. The enzyme
      activity of transgenic strain was higher than that of the wild type. It may be
      the first report on transformation of detoxify gene of pesticide resistant culex
      into Synechococcus strain.

PMID- 10883275
TI  - [High expression of human EPO gene in the larvae and pupae of the silkworm,
      Bombyx mori].
AB  - Erythropoietin (EPO) is a glycoprotein hormone produced primarily by the kidney,
      and is principal factor regulating red blood cell poduction. The synthesized EPO
      cDNA was inserted into the transfer vector pBlueBac III to generate the
      recombinant transfer plasmid pBlueBacEPO. Cotransfection of BmN cells with
      pBlueBacEPO DNA and Wild BmNPV DNA generated the recombinant virus rBmNPVEPO
      carrying EPO gene driven by the strong promoter of AcNPV polyhedrin gene. The
      results of Southern blot and PCR reaction confirmed that EPO gene had been
      correctly inserted in the target position in the BmNPV genome. ELISA assay showed
      that the EPO gene was expressed with high level in the larvae and pupae of the
      silkworm. The larvae and pupae produced as high as 62,800 u and 74,000 u in 1 mL
      hemolymph on the 4th day (larve) and the 5th day(pupae) after infection with the
      recombinant virus rBmNPVEPO, respectively. Western blot analysis showed the
      molecular weight of rhEPO produced in the lavae or pupae was about 26 kD.
      Biologic assay showed the rhEPO had high activity (about 63,000 u in per
      milliliter of hemolymph) in vitro.

PMID- 10883276
TI  - [Growth and metabolism of hybridoma cells in semicontinuous perfusion cultures].
AB  - The growth and metabolism of WuT3 hybridoma cells were studied in semicontinuous
      perfusion cultures. The growth of cells, utilization of glucose, production of
      lactate, ammonia and monoclonal antibody were investigated. As the perfusion rate
      increased from 1.0/d to 2.0/d, the lactate yield coefficient from glucose
      Ylac/glu decreased 18%, the ammonia yield coefficient from glutamine Yamm/gln
      decreased 40%, the alanine yield coefficient from glutamine Yala/gln increased
      58%, the glycine yield coefficient remained almost constant. This indicate that
      cells would regulated their metabolic flux at higher cell density, and glutamate
      produced in quantity and pyruvate would turn into alanine rather than glycine by
      transamination. As a result, potentially toxic effects were reduced because less
      ammonia and lactate were produced.

PMID- 10883277
TI  - [Enzymatic resolution of racemic naproxen in a low aqueous-organic biphase
      system].
AB  - A stereoselective hydrolysis of the racemic naproxen methyl ester by immobilized
      lipase from Candida rugosa in a low aqueous-organic biphase system was studied.
      Support polar, water content, the logP value of organic phase and product
      inhibition effected the activity of immobilized enzyme. According to these
      reaction conditions, a low aqueous-organic biphase system for the continuous
      production of (S)-(+)-Naproxen was developed. The reaction was carried out in a
      continuous-flow closed-loop 50 mL stirred bioreactor packed with YWG-C6H5, a
      poorly polar synthetic support on which the lipase had been immobilized by
      adsorption. The aqueous phase was permanently remained in the reactor associated
      with the immobilized enzyme particles; the organic phase containing substrate was
      pumped through this reactor and emerged with the products. The continous-flow
      stirred bioreactor containing 75 mg lipase was allowed to operate continuously
      for 60 days at 30 degrees C with a 25% loss of activity, 900 mg of (S)-(+)
      Naproxen (eep 95%) were producted.

PMID- 10883278
TI  - [A study on screening and high density cell cultivation of a yeast strain
      Kluyveromyces with high inulinase yielding and its enzymology properties].
AB  - A yeast strain Kluyveromyces with high inulinase yield was screened. The highest
      inulinase activity of 288.78 u/mL was reached when a high cell density
      cultivation method was developed for inulinase production. It was 6.8 times
      higher than the highest level reported in the same species. The activity ratio of
      its inulinase to invertase was 1/24.72, the Km values were 13.3 mmol/L and 62.6
      mmol/L when inulin and sucrose were used as substrate, respectively; The optimum
      pH value was 4.4, this enzyme also showed a good pH adaptability and stability,
      i.e. more 90% of the highest level was maintained between pH 3.8 and 5.6; The
      optimum reaction temperature was 55 degrees C, higher activity was maintained
      between 50-57.5 degrees C, its half life period was 16 hours at 55 degrees C; It
      was found for the first time that addition of magnesium ion into the reaction
      system increased the enzyme activity by 11%.

PMID- 10883280
TI  - [Separation and purification of taxol using normal- and reversed-phase
      chromatography in tandem].
AB  - A method is described for separation and purification of taxol from the extract
      of Taxus cuspidate callus culture with Al2O3 normal-phase chromatography and C18
      reversed-phase chromatography, The operating conditions of the two
      chromatographic steps were investigated and optimized. The content of taxol was
      greatly increased after Al2O3 chromatography. The purity of taxol reached 95%
      from less than 1.0% after the two chromatographic steps. The final purity of
      taxol was more than 98% after the process of crystallization. The 13CNMR spectrum
      of the product was identical to that of taxol reported in the literature.

PMID- 10883279
TI  - [Expression and characterization of HIV-1 Gag p17-p24 protein].
AB  - The biological and immunological characteristics of HIV-1 core protein p17-24
      expressed by recombinant vaccinia viruses were studied. The results of indirect
      immunofluorescence assay (I-IFA), Western blot and dot ELISA showed that the two
      recombinants could express the p24 gag and p17-24 gag fusion proteins in infected
      cell lines respectively. The electromicroscope observation revealed that the
      expressed proteins could also assemble into virus-like particles. The recombinant
      vaccinia viruses can also stimulate mice for the formation of anti HIV-1 Gag p24
      antibody. When infected with the recombinant viruses, the chromosome DNA ladder
      caused by the apoptosis of the BHK cell was observed.

PMID- 10883281
TI  - [Immobilized Ni(2+)-IDA metal chelating affinity membrane chromatography for
      purification of commercial human serum albumin].
AB  - Further purification of commercial human serum albumin was studied on immobilized
      Ni(2+)-IDA composite membrane cartridge. Effect of pH on HSA binding capacity was
      examined. A lot of impurities in the commercial HSA had been removed by a single
      step purification with a recovery of more than 85% of the protein bound on
      membrane cartridge. The purified HSA was of comparable purity of that from Sigma
      company analyzed by capillary electrophoresis. The nickel ion retained in the
      protein solution could be removed efficiently with the N, N, N'-tris
      (carboxymethyl) ethylenediamine chelating membrane cartridge.

PMID- 10883282
TI  - [Effects of a few nutritional factors on content of coenzyme Q10 by tobacco plant
      cells in suspension culture].
AB  - With suspension cultured cells of tobacco (Nicoliana Tobacum L.), effects of
      inorganic phosphate, nitrogen sources and carbon source on cell growth and CoQ10
      content were investigated. It showed that, When treated with 30 g/L of sucrose,
      the total amount of CoQ10 was highest (8212 g/L); and the cell biomass and CoQ10
      content were 19.8 micrograms/L, 414.7 micrograms/g(dwt) respectively. When
      treated 340 mg/L of KH2PO4, the cell biomass, the content and total amount of
      CoQ10 were 21.04 g/L, 514.5 micrograms/g(dwt) and 10824 micrograms/L
      respectively. When treated with the ratio of NH4+/NO3- was 1:2, the cell biomass,
      the content and total amount of CoQ10 were 21.04 g/L, 514.3 micrograms/g(dwt) and
      10,820 micrograms/L respectively. The high ration of NH4+/NO3- was suitable for
      the formation of CoQ10, but not for the cell growth.

PMID- 10883283
TI  - [Construction and expression of anticolonic cancer scFv fragment].
AB  - Anticolonic cancer scFv fragment with a VH-linker-VL structure was constructed
      and expressed in E. coli. SDS-PAGE analysis showed the fragment cloned in pComb3
      was not expressed efficiently in JM83, while cloned in pET-22b(+) highly
      expressed in BL21(DE3) up to 35.5% of the total bacterial protein obtained, if
      the culture was incubated under 30 degrees C.

PMID- 10883284
TI  - [Construction and expression of a hepatocellular carcinoma specific rodent and
      its humanized single-chain Fv fragments in Escherichia coli].
AB  - The aim of this research is to exploit the expression strategies for two genes
      encoding a rodent and its humanized version single-chain fragments(scFv) specific
      for hepatocellular carcinoma (HCC) and compare these two scFves in antigen
      binding activity. Three vectors were used to express these two genes in different
      routes of fusion pathway, secrete pathway and intracellular pathway. The refolded
      single-chain antibodies were examined by antigen capture ELISA. Results showed
      that inclusion bodies were produced in all of the applied vectors despite of
      variation of IPTG concentration and culture temperature. Cell ELISA and binding
      competition inhibition indicated that the humanized single-chain Fv retained the
      similar affinity as its rodent counterpart. These results implied that the
      solubility of genetic antibodies are determined primarily by its amino acids
      sequence; The adopted humanization strategy in previous design made little effect
      on the natural conformation of complementarity-determining regions(CDR) of the
      parent antibody. The humanized HCC specific scFv can be further evaluated and
      developed as therapeutics.

PMID- 10883285
TI  - [AFLP analysis of photoperiod-sensitive genic male sterile(PGMS) rice mutant
      lines].
AB  - The reaction conditions for rice AFLP assay were optimized. The relative
      efficiencies for polymorphism detection of RFLP, RAPD and AFLP were compared
      through the analysis between a pair of PGMS allelic mutant lines(NK58S and
      NK58F). Results indicated that the efficiency for polymorphism detection in rice
      is in the order of AFLP > RAPD > RFLP, and also indicated that AFLP is a powerful
      DNA molecular marker technique for polymorphism detection, especially in the
      cases of extremely low polymorphism, such as isogeneic lines and allelic mutant
      lines. The advantages and disadvantages of these three molecular marker systems
      were discussed. Using AFLP in conjunction with bulked segregating analysis, 5106
      AFLP loci were screened and 9 of them showed polymorphism between NK58S and
      NK58F, 4 of the polymorphic AFLP products were cloned, Southern bloting analysis
      showed that two of them were single copy sequences while the other two were low
      copy sequences in rice genome.

PMID- 10883286
TI  - [Ribozyme which specifically cleave 12-lipoxygenase mRNA: in vitro activity and
      its dynamics].
AB  - The ribozyme gene which specifically cleaved 12-lipoxygenase mRNA was designed,
      synthesized and cloned according to hammer-head ribozyme model. A 25-bp-long
      segment of 12-lipoxygenase mRNA was chemically synthesized as substrate, which
      was incubated with transcribed ribozyme RNA to detect its cleavage activity in
      vitro. The results showed that the ribozyme had a relatively high cleavage
      activity against 12-lipoxygenase mRNA segment at 37 degrees C. It's kcat value
      and Km value was 0.083/min and 1300 nmol/L respectively. The ribozyme had a very
      high activity at 50 degrees C and its kcat value was 0.31/min.

PMID- 10883287
TI  - [Effects of media on the production of flavonoids by suspension cultures of
      Saussurea medusa].
AB  - Flavonoids were produced from cell suspension cultures of Saussurea medusa. The
      results of studies on eight types of culture media showed that the MS medium was
      the best for cell growth and flavonoids formation, We investigated the effects of
      all the components of MS medium on the cell growth and flavonoids production, and
      found that carbon, nitrogen and phytohormone had especially marked effects. With
      MG medium a modified MS medium, the yield of cell growth was 24.8 g(dwt)/L, with
      MP medium another modified MS mediums, the yield of flavonoids production was 1.
      75 g/L. The yield of cell growth and flavonoids production in MG and MP medium
      were 32% and 70% higher than that in MS medium respectively.

PMID- 10883288
TI  - [Studies on fermentation conditions for the accumulation of poly-beta
      hydroxybutyrate in Alcaligenes eutrophus].
AB  - The results of the cultivation of Alcaligenes eutrophus showed that nitrogen
      limitation or exhaustion could stimulate the substantial accumulation of PHB. But
      the exhaustion of nitrogen source in PHB formation period would result in the
      rapid drop of PHB synthetic rate. Oxygen limitation could also stimulate the
      formation of PHB, but the content of PHB in the cell was much less than that in
      case of nitrogen controlled conditions. Obvious influences were observed on PHB
      fermentation when ammonia water feeding was stopped at different cell growth
      phases, and better results could be obtained when it was performed at 20 g/L to
      30 g/L of residual biomass. Cell dry weight, PHB content and PHB concentration
      reached 61.9 g/L, 80.5% and 49.0 g/L, respectively under desired conditions.

PMID- 10883289
TI  - [Study of the factors of Cr(III) bioaccumulation on Spirulina platensis].
AB  - Some factors of Cr(III) bioaccumulation on Spirulina platensis were studied in
      detail. It was found that the bioaccumulation of Cr(III) on Spirulina platensis
      involved two steps: rapid adsorption and slow absorption. Chromic(III) compounds
      with weaker chemical bond had higher bioaccumulation efficiency. Under the same
      algal cell concentration, Cr(III) bioaccumulation rosed up with Cr(III)
      concentration. On the other hand, with Cr(III) concentration not changed, the
      total bioaccumulation of Cr(III) on Spirulina platensis increased with algal cell
      concentration, but the Cr(III) bioaccumulation on unit algae reduced. The study
      also showed that Spirulina platensis powder could bioaccumulate more Cr(III) than
      fresh Spirulina platensis, pH is a quite important factor and more suitable pH
      for Cr(III) bioaccumulation is 7. It was also proved that Cr(III) bioaccumulation
      benefited from the increase of temperature and light intensity. Cations had
      either stimulation or inhibition effects on the Cr(III) bioaccumulation on
      Spirulina platensis.

PMID- 10883290
TI  - [Cloning of human TRAIL cDNA and its expression in COS-7 cells].
AB  - The human TRAIL cDNA was amplified with the total RNA from the human acute
      promyelocytic leukemia cell line HL-60 by means of RT-PCR, and was cloned into
      the pGEM-T vector. The DNA sequence analysis showed that it was consistent with
      the published sequence. Then, the insert of human TRAIL cDNA was subcloned into
      the mammalian expression vector pcDNA3. The hybrid plasmid pcDNA3-hTRAIL was
      transformed into COS-7 cells, and transiently expressed in the COS-7 cells. The
      activity of the expressed product could induce apoptosis in U937 cell line.

PMID- 10883291
TI  - [Synthesis of dicarboxylic esters by lipase].
AB  - The syntheses of dicarboxylic esters by immobilized lipase from Candida sp.--1619
      were investigated. The reaction system was composed of 1 mmol dicarboxylic acid,
      2 mmol alcohol, 3 mL hexane and 15 mg celite-adsorbed immobilized lipase(300 u),
      in a closed 100 mL Erlenmeyer flask, shaken at 40 degrees C for 5 h. Sebacic acid
      was the best substrate among nine dicarboxylic acids selected. Among the 18
      saturated fatty n-alcohols, the alcohols with carbon chain length rangin from C4
      C18 had good reactivity. The primary alcohols had much better reactivities than
      corresponding secondary alcohols and multihydroxy-alcohols. Tertiary alcohols
      showed no reactivity. Hydrocarbons, benzene, toluene, xylene and tetrachloride
      were favorite reactants among 15 organic solvents selected, in none-solvent
      stationary system, (5 mmol sebacic acid, 10 mmol dodecanol, 150 mg immobilized
      lipase(3000 u)) reacted without plug for 3.5 h, the optimum temperature was 60
      degrees C. The conversion degree was over 92% when reaction carried out at 50-90
      degrees C for 17 h. The suitable reaction pH ranged from 6-8. The reactant was
      developed on GF254 plate (hexane:ethyl ether:acetic acid = 30:20:1 (V:V:V). There
      were three spots with different Rf value at 0.96, 0.55 and 0 corresponding to
      product, oleyl alcohol and sebacic acids, respectively.

PMID- 10883292
TI  - [Effects of dietetic supplementation with L-arginine in cancer patients. A review
      of the literature].
AB  - It has been suggested that the administration of certain nutrients may improve
      the immune response of patients with cancer. Experimental studies have shown that
      deficiencies in specific amino acids have a worse effect on humoral immunity than
      they do on cell-mediated immunity because they impair antibody synthesis. Here,
      arginine plays a particularly important role, and research with several
      experimental and human tumor models to determine the therapeutic utility of this
      amino acid is under way. In this paper, we review current literature on the use
      of arginine as pharmacologic nutritional support for cancer patients. Dietary
      supplementation with arginine has been shown to benefit these patients by
      reducing the growth of transplantable tumors, the incidence of metastases, and
      the tumor-producing potential of carcinogens. However, results observed in humans
      have given rise to controversy regarding the optimal dosage of arginine
      supplementation and the types of cancer best treated with amino acids. Further
      prospective and randomized studies will be necessary in order to determine the
      proper utilization and the therapeutic benefits of such dietary supplementation.

PMID- 10883293
TI  - [Wheat bran and breast cancer: revisiting the estrogen hypothesis].
AB  - Breast cancer is the most relevant form of cancer among women in Latin America.
      Many studies have evaluated the hormonal mechanisms involved in mammary
      carcinogenesis, although new focus is aimed towards factors that can potentially
      be used individually to reduce risk. Wheat bran seems to show a consistent
      protective effect in mammary carcinogenesis. Wheat bran, besides high level of
      insoluble fiber, also contains phytic acid and lignins, phytochemicals that have
      shown to inhibit in vitro and in vivo growth of mammary cancer. The protective
      effect of wheat bran in breast carcinogenesis is greatest at the promotional
      phase and when supplemented to a high fat diet. Doses of wheat bran in the 9-12%
      range have been consistently protective and the inconsistencies observed at
      higher doses may be dependent on the animal model used. This review examines the
      protective role of wheat bran in the development of breast cancer and the
      possible mechanisms involved.

PMID- 10883294
TI  - [Nutritional status of vitamin A in mother/newborn pairs from 2 hospital
      nurseries in Rio de Janeiro, Brazil].
AB  - The aim of the present study was to assess maternal and newborn (umbilical blood)
      vitamin status in 220 mothers/newborns at birth from two public health centers in
      Rio de Janeiro, Brazil. The proportion of low retinol levels (cut-off point 1.05
      mumol/L) in the umbilical cord of newborns (55.4%) was greater than found in
      their mothers (23.6%). A highly significant correlation (X2 = 14.2; p < 0.0001)
      was found between the levels of retinol of mothers and newborns. The overall
      prevalence of low levels of retinol in the mother was 23.6% whereas that of
      newborns was 55.4%. Umbilical cord mean concentration less than 1.05 mumol/L was
      significantly lower (2.49 +/- 1.08 mumol/L) in mother with vitamin A deficiency
      (3.21 +/- 0.97 mumol/L; p < 0.0001). Low birth weight was associated with vitamin
      A deficiency (X2 = 6.86; p < 0.01). These data reinforce the need for close pre
      natal attention in vitamin A status.

PMID- 10883295
TI  - Vitamin A status of pregnant women assessed by a biochemical indicator and a
      simplified Food Frequency Questionnaire.
AB  - The aim of this study was to compare plasma concentrations of vitamin A in 710
      women after delivery, with a simplified Food Frequency Questionnaire (FFQ).
      Vitamin A was determined in plasma, by HPLC. The FFQ included 55 foods, and was
      based on the typical diet of the low socioeconomic families in the Southeast of
      Brazil. For calculation purposes, first were identified all potential sources of
      retinol and carotenoids; the portion sizes being assigned to each food item on
      the basis of a previous study in the same area. Daily, weekly and monthly
      frequencies of consumption of foods with high, moderate and low concentrations of
      vitamin A were grouped according to the IVACG recommendations (1) in usual
      pattern of food consumption (UPF) scores. Pregnant women were allocated by these
      scores in 3 different categories (high, moderate and low) according to their risk
      of developing vitamin A deficiency. The categories of risk were based on the safe
      level of vitamin A intake of 800 RE/day (5600 RE/week) (7) and the basal
      requirement of 370 RE/day for pregnant women (8). 1.3% of the women had plasma
      concentrations of vitamin A < or = 0.70 mumol/l, 10.2% between 0.71-1.05 mumol/l
      and 88.5% > 1.05 mumol/l. According to the score categories, 49.5% of the women
      were at low risk for vitamin A deficiency, and 50.5% were at moderate risk. There
      was a weak statistically significant correlation between the plasma
      concentrations of vitamin A and the score categories (r = 0.11; p = 0.005). Our
      results indicate that the FFQ does not provide a very precise information on
      vitamin A status, probably because of the day to day variation in vitamin A
      intake, and the insensitivity of plasma concentrations to consumption of vitamin
      A. However, by using a simple score based on the FFQ, we were able to predict
      that the majority of the mothers were not at high risk for vitamin A deficiency.

PMID- 10883296
TI  - [Nutritional status and clinical evolution of hospitalized Chilean infants with
      infection by respiratory syncytial virus (RSV)].
AB  - Respiratory syncycial virus (RSV) is the first cause of acute lower respiratory
      tract infection in Chilean infants. A significant impact of nutrition on clinical
      course of these infections has been described. In order to analyze the
      association between nutritional status (NS) and clinical course of infants
      hospitalized with acute lower respiratory tract infection due to RSV, 130 infants
      (mean age 5.8 +/- 4.9 m) without chronic diseases, admitted to hospital with
      confirmed RSV infection, were studied. Clinical course of disease was assessed
      (hospitalization days and days with oxygen therapy) according to nutritional
      status on admission (weight/length (W/L), ratio, arm muscle area, lymphocyte
      count and albumin), antropometrics changes, and hospital dietary intake. On
      admission prevalence of malnutrition by W/L (z score) was 1%, 14% overweight and
      8% were obese. Median value of hospitalization days was 5 d (2-29 d) and days
      receiving oxygen was 3 d (0-19 d). Longer admission were observed in fasted
      patients than in those who were fed everyday (Wilcoxon and Log-rank test, 8 d vs
      5 d; P < 0.01). Obese children (Wilcoxon and Log-rank test, 5 d vs. 3d in normal
      patients; P < 0.05), and patients not fed enterally (Wilcoxon and Log-rank test,
      7 d vs. 3 d; P < 0.01) required oxygen for longer time. Fasting and severity of
      illness (Tal score) were correlated variables (X2 0.001). The multivariate
      analysis showed an association of Tal score and NS on admission, with days
      receiving oxygen therapy. We conclude that obesity is a risk factor for worse
      clinical course of acute lower respiratory tract infection in Chilean infants
      with RSV infection and without chronic disease.

PMID- 10883297
TI  - [Relationship between food habits and serum cholesterol levels in a suburban
      population in Argentina].
AB  - Studies of cholesterol levels in a population of Gran Buenos Aires was made in
      1983, 1988, 1993 and 1996, and the Argentinian alimentary habits in this period
      were analyzed. It was noticed a change in food consumption, with reduction in the
      intake of fatty foods, such as meat, butter, milk, and other dairy products, with
      the concomitant increment in fiber rich products and oil, meat and dairy products
      reduced in fats. Changes in serum cholesterol level were analysed in 3051 persons
      along 1983-1996. They were grouped according their age and sex: A) 1-6 years old,
      B) 6-12, C) 12-17, D) 17-30, E) 30-60, F) 60-80. It was observed an increment in
      cholesterol level with age. For each group during the first 10 years of study was
      noticed a constant decrease in total cholesterol being higher in women than in
      men and according with the alimentary changes. Group D in 1983 became group E in
      1993, maintained their cholesterol level along 10 years of life, being lower than
      the corresponding E group of 1983, while the older ones did not present
      differences. Values of cholesterol/cholesterol-HDL index over 6.5 correlate with
      a high incidence in cardiovascular diseases. The 40% of the population studied
      during 1993 and 1996 was evaluated, and the maximum average value found was 4.90.
      These results suggest that reduction in fat intake and diversification in food
      consumption during this period has contributed to decrease cholesterol levels and
      cholesterol/cholesterol-HDL index, particularly in younger than 30 years old and
      women, contributing to reduce metabolical cardiovascular diseases.

PMID- 10883298
TI  - [Changes in lipid profile in obese children and adolescents].
AB  - Alterations in plasmatic lipid profile are known to be risk factors for
      atherosclerotic disease and have been associated with obesity. This research was
      designed in order to study the incidence of these alterations in obese children
      and adolescents according to two different reference patterns. Analyses of seric
      levels of Total Cholesterol (CT) and fractions and of Triglycerides (TG) were
      done. The sample included 74 obese children and adolescents with average age
      equal to 11 years and 10 months for boys and 10 years and 9 months for girls and
      with mean weight/height ratio (W/H) equal to 151 and 149% for boys and for girls,
      respectively. Plasmatic lipid values obtained were classified according to the
      American Heart Position Statement Circulation (AHPSC) and to Kwiterovich
      reference patterns. It was observed that patients with abnormal seric HDL
      cholesterol (HDL) levels had a significantly greater (W/H) then the other group.
      It was also noticed that a greater number of individuals presented abnormal or
      borderline plasmatic lipid levels (91.9%), specially HDL (93.6%) and TG (67.6%),
      according to Kwiterovich than AHPSC. Obesity showed to be an important factor in
      determining lipid profile values and should be included as a variable to indicate
      screening of these lipoproteins in childhood and adolescence.

PMID- 10883299
TI  - [Comparison of 2 anthropometric methods for the estimation of frame size in
      Venezuelan adults].
AB  - The frame size improves the interpretation of the body mass in adult and its
      incorporation is very useful in the assessment of nutritional status. This study
      compared two of the anthropometric methods used to classify individuals according
      to frame size: Grant method (height (cm)/wrist circumference (cm)) and Frame
      index 2 (elbow breadth (mm)/height (cm) x 100) in order to identify coincidence,
      concordance and divergence between then. Data from two hundred and forty nine
      apparently healthy individuals, between the ages of 22 and 63, belonging to
      "Health Project: Administration employees of the Simon Bolivar University" were
      included. Results showed significant differences between the two methods, not
      only in the proportion of classified individuals in each frame size category, but
      also when contrasted the same method using one or another body hemispheres. When
      studying both methods, the divergence in frame size identification varied between
      19% and 55% with a low concordance (k = < or = 0.40). Grant method, compared to
      Frame index 2 showed a greater association with the variables and indicators of
      total body mass and body fat; in the other hand, Frame index 2 revealed a lesser
      correlation with such variables and indicators specially in female (r = 0.17 with
      fat percentage). These results clearly show the differences that could be created
      in the frame size identification of an individual of group of individuals if
      different criteria are used; this could also lead to a wrong anthropometric
      diagnosis.

PMID- 10883300
TI  - [Effect of 3 storage temperatures on the quality of kiwi fruit pulp concentrated
      at a reduced pressure].
AB  - The effect of three storage temperatures (0, -9 and -18 degrees C) of the kiwi
      fruit pulp reduced pressure concentrate, by a period of 3 months, in the physical
      (soluble solids, water activity, consistency and color), chemistry (pH, acidity,
      ascorbic acid, chlorophyll and pheophytin) and sensorial (appearance, aroma,
      acidity, sweetness, color and flavor) characteristics were studied. The greater
      deterioration was produced in the stored pulp to 0 degree C, while to -9 degrees
      C there is no significative differences, on the other hand, the kiwi-fruit pulp
      stored to -18 degrees C maintained large part of the original characteristics. It
      was observed that while the temperature and storage time increased, vitamin C and
      chlorophyll contents decreased, varying significantly consistency, color and
      appearance of product. The rest of the analyzed variables did not present
      significative differences during storage.

PMID- 10883301
TI  - [Listeria monocytogenes incidence and evaluation of the sanitary quality of
      filleted fresh fish from the Metropolitan Area of San Jose].
AB  - Fish constitutes a very important part of human diet due to its protein content.
      The poor commercialization system existing in Costa Rica for this product causes
      an important secondary contamination that may include microorganisms such as
      fecal coliforms, Staphylococcus aureus and even pathogens such as Listeria
      monocytogenes. There is a lack of recent information about the microbiological
      quality of the fish that arrives to the Metropolitan Area of San Jose, Costa
      Rica, so the aim of this work was to study it through the detection of
      microbiological indicators and the incidence of L. monocytogenes. Five different
      samplings were realized to 27 fisheries located in two different areas from San
      Jose, Costa Rica: the Central Market and the rest of the Metropolitan Area. Each
      time, a 500 g sample of fresh filleted fish was taken and transported to the Food
      Microbiology Laboratory, Universidad de Costa Rica, for performing the different
      analysis, which included the presence/absence of L. monocytogenes, total plate
      count, total and fecal coliforms count and Most Probable Number of Staphylococcus
      aureus. Also, a hygiene evaluation of the different fisheries was performed.
      According to this, 22.2% of the fisheries were classified as excellent, 14.8% as
      good, 40.8% as regular and 22.2% as bad. Fisheries hygiene is independent of the
      incidence of L. monocytogenes with a 95% confidence level, and there is no
      significant relationship between hygiene and the other indicators analyzed. There
      is a significant relationship between the incidence of Listeria sp. and the
      hygiene of the Central Market area. It was determined that 96.3% and 29.6% of the
      fisheries accomplish with the microbiological limits established by ICMSF for S.
      aureus and total plate count, respectively. Listeria sp. was found in 65.2% of
      the fish samples analyzed. From these, 52.3% was L. monocytogenes, 43.2% L.
      innocua, 3.4% L. ivanovii and 1.1% L. seeligeri. In 88.9% of the fisheries the
      presence of L. monocytogenes was positive at least once.

PMID- 10883302
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
      pnuemoniae, 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- 10883303
TI  - [Food effects on some reproductive aspects of rainbow trout, Oncorhynchus mykiss,
      in a Venezuelan fish farm].
AB  - Samples of rainbow trout, Oncorhynchus mykiss, were fed with three different
      dried diets, labeled D1, D2 and D3, the first ones were expanded and the last one
      pelleted type food. Their protein content ranged from 36% to 42%, and only D1
      diet presented a pigment in its composition. The gonodasomatic index (GSI) as
      well as the gonadial development showed a different behavior in males and females
      for all the samples tested. A continuous sperm production was observed in males
      fish, while in female fish the GSI showed a tendency to increase through the
      whole study, and they showed a reproductive rest period on july 92. Fish relative
      fecundity and egg diameter were similar in all cases. The gonodial maduration age
      was shorter for the female that were fed with D1 and D2, while the 50% of the
      trout population that got D3 had a gonodial maduration period two months longer.
      For all trouts tested the fertility was low with a maximum value of 49%. The
      hatchery from the tested trouts with D2 intakes had a mortality value of 62%.
      Meanwhile, those with D1 and D3 intakes showed mortality values of 36% and 43%
      respectively.

PMID- 10883304
TI  - [Vegetable resources with agroindustrial potential from Guatemala. Chemical
      characterization of the pulp and of the seeds of Theobroma bicolor].
AB  - T. bicolor grows wild in certain regions of Guatemala. The fruit is utilized by
      the rural population for the preparation of drinks from the pulp and the seed,
      replacing cocoa (T. cocoa). The fruit of T. bicolor used in the present study,
      measured on the average, 15 cm long and had an average weight, of 752 g. The
      pulp, the shell, and the seed represented 23.8, 62.5, and 13.7%, respectively, of
      the fruit weight. The pulp contained on the average, 38 seeds/fruit, which
      weighted on the average, 1.11 g and were 2.4 cm long. T. cacao seeds weighted
      0.62 g and were 1.6 cm long. The protein content (24.42%) and fiber content
      (30.86%) of the T. bicolor seeds, was greater than those from T. cacao, although
      fat content was lower (25.48%). The fat of the seeds of T. bicolor has different
      physicochemical characteristics than the fat of the seeds of T. cacao, such as
      melting point, iodine value, and saponification number. The seeds of both, T.
      cacao and T. bicolor, were used for the preparation of a local drink using
      toasted corn flour, sugar, and anatto flour in equal preparations, with and
      without toasted whole soybean flours (6.25%). Through a sensory ranking trial, it
      is established that the drink from T. bicolor and soybeans, was preferred over
      other preparations with T. cacao. The pulp of T. bicolor with an interesting
      chemical composition, yielded an aromatic pleasant drink, and from T. bicolor, is
      an interesting resource for industrialization and for genetic characteristics for
      T. cacao improvement.

PMID- 10883305
TI  - [Vitamins and minerals from sardine in tomato sauce, from the Mexican Pacific
      fish zones].
AB  - Sardine is a sea food widely consumed in Mexico due to it's abundance and very
      low price. Its content in vitamins, minerals and chemical composition were
      evaluated in its canned presentation in tomato sauce. Samples proceeded from 3
      fishery areas of the Mexican Pacific: (L1) Baja California Sur, (L2) Sonora and
      (L3) Sinaloa. The proximal chemical analysis was carried out by the AOAC methods;
      mineral content (Ca, Mg, Na, K, Fe, Zn, Cu, Cd, Cr, Pb) was determined by atomic
      absorption spectrophotometry and vitamins A, B1, B2 and niacin were quantified by
      HPLC. Results showed a high moisture content from 69 to 82%, ether extract ranged
      between 7.8% (L2) and 10.2% (L3) and crude protein content between 10.6% (L3) and
      14.6% (L1). Vitamin A (IU/100 g) was similar for all samples: L1 (63-66); thiamin
      (mg/100 g) was high in L1 (0.13) and low in L3 (0.09); riboflavin was high in L1
      (0.15) and showed values of 0.13 for both L2 and L3; niacin content was high in
      all samples: L1 (2.24), L2 (1.48) and L3 (1.75). Minerals were abundant (mg/100
      g) in Na, K, and P; L1 showed a great variation for Na (363-636) compared with L2
      and L3 (250); K was very variable among the samples: L1 (597), L2 (100) and L3
      (57). Phosphorous and magnesium had small variations: P (229, 243 and 212) and Mg
      (28, 23 and 23) for L1, L2 and L3. Iron was more abundant in L1 (5.5) and L3
      (4.3); Zn was higher in L2 (3.4) and similar in L1 (2.5) and L3 (2.2). Copper
      showed a great variation in L2 (0.21-0.48) but the averages were similar (0.37,
      0.35, 0.33, for L1, L2 and L3 respectively). Finally, heavy metal content was
      lower than 0.002 mg/100 g. In conclusion, there are some variation in Ca, Na, K,
      thiamin and niacin content in canned sardine with tomato sauce, depending upon
      the fishing area.

PMID- 10883306
TI  - [Chemical composition and digestibility of the protein of 20 ecotypes of Pijiguao
      (Bactris gassipaes) of the Venezuelan Amazon].
AB  - Precooked flour (80 degrees C x 3 hours) from the pulp of 20 ecotypes of Pijiguao
      cultivated in the Amazon area of Venezuela and dried at 80 degrees C for 3 hours
      was manufactured for the purpose of developing an alternative method of
      conservation of the fruit for human consumption and for the purpose of
      contributing to the study of the germoplasm through the assessment of its
      chemical characterization by applying the AOAC methods. The results showed a wide
      statistical variability (p < 0.05) among the ecotypes in relation to the fat
      content (5.13%-17.30%), protein content (5.00%-8.30%), starch content (29.13%
      56.40%), and dietetic fiber content (8.10%-21.00%). Likewise, significant
      differences in the carotenoid content (3.46-40.06 mg/100 g) and the vitamin C
      content (6.60 to 51.60 mg/100 g) were also detected. The digestibility "in vitro"
      of the protein was high (88.10%-91.90%). In addition color was analyzed in a
      tristimulus color meter and the data varied between L = 65.07 to 81.84; a = 0.18
      to 13.96 y b = 18.30 to 38.82. Orange, yellow, and beige were observed Pijiguao
      precooked flour is a potential source of dietetic carotenoids, vitamin C, fat,
      and starch.

PMID- 10883307
TI  - [In memoriam: Jose Vicente Martins Campos].

PMID- 10883308
TI  - [Breath hydrogen test to evaluate lactose absorption and small bowel bacterial
      overgrowth in children].
AB  - The aim of this study was to determine the lactose absorption capacity and
      possible existence of bacterial overgrowth in the small bowel in asymptomatic
      school children of low social economic level in Marilia, a city located in the
      interior of Sao Paulo state. Eighty three children aging 7 to 15 years old
      without any gastrointestinal manifestations at least 30 days prior to the tests
      were studied. All the patients had fasted for at least 8 hours before the tests
      were performed. Lactose absorption was evaluated by breath hidrogen test after an
      overload of lactose 18 g in 10% aquous solution. Lactose intolerance was
      determined by the occurrence of clinical symptoms, such as diarrhea, abdominal
      pain, flatulence, etc in the following 24 hours after the test was performed.
      Bacterial overgrowth was evaluated by the breath hidrogen test after a 10 g
      lactulose load in aqueous solution. Lactose malabsorption was detected in 19
      (22.9%) children and lactose intolerance was observed in 10 (12%) children.
      Lactose intolerance was more frequently observed in children who showed lactose
      malabsorption (6/19; 31.6%) than in those who presented a normal test (4/64;
      6.3%) (P = 0.008). Bacterial overgrowth was detected in six (7.2%) children and
      showed no statistical relationship with lactose malabsorption. Ontogenetic
      lactose malabsorption verified in this group of school children is similar to the
      reported for Caucasian populations. Presence of bacterial overgrowth confirms the
      existence of asymptomatic environmental enteropathy in children of low social
      economic level.

PMID- 10883309
TI  - [Comparison of IgA class reticulin and endomysial antibodies for the diagnosis
      and dietary control in celiac disease].
AB  - Sensibility to gluten is a condition with high immunological reaction against
      gluten proteins from wheat, barley, rye and oats in individuals genetically
      susceptible. Celiac disease is its most frequent expression with various forms of
      clinical presentation. The treatment consists in gluten free diet. Although the
      biopsy of proximal small bowel is necessary, the importance of serological tests
      is increasing in the screening, diagnosis and monitoring of gluten free diet in
      celiac patients. The aim of this study was to investigate the presence of
      antiendomysium (EmA-IgA) and anti-reticulin (ARA-IgA) antibodies in 56 celiac
      patients (17 at diagnosis, 24 adherent to the diet and 15 with transgression to
      the diet). The antibodies were detected by indirect immunofluorescence, using
      human umbilical cord as substrate for the EmA-IgA and rat liver and kidney for
      the ARA-IgA. In the patients at diagnosis and in the group with transgression to
      the diet the total positivity was 100% for EmA-IgA and 59.4% for ARA-IgA.
      Antibodies were not detected in gluten-free diet patients. Among the 32 positive
      patients, the concordance of both tests was of 59.4% (19/32), being 40.6% (13/32)
      negative to ARA-IgA and positive to EmA-IgA. No patient was positive for ARA-IgA
      and negative for EmA-IgA. Thus, the sensitivity for EmA-IgA was of 100% and 59.4%
      for ARA-IgA. The association of the two tests did not improve the positivity in
      the samples. In conclusion, EmA-IgA can be considered the best serological test
      for diagnosis and follow up of celiac patients, because it presents high
      predictive value, high specificity and sensibility and is not expensive if using
      human umbilical cord as substrate.

PMID- 10883310
TI  - [Prolonged neonatal cholestasis: prospective study].
AB  - Due to the urgency in choosing either clinical treatment or immediate surgical
      intervention, the study of the prolonged neonatal cholestasis involves two basic
      aims: the differential diagnosis between biliary atresia and neonatal hepatitis
      and the research into the associated etiological agents. So, in a prospective
      trial carried out in the 70's, 77 children with prolonged neonatal cholestasis
      were studied in order to establish the differential diagnosis between biliary
      atresia and neonatal hepatitis, followed by the evaluation of 108 children
      towards a pathogenesis of the prolonged neonatal cholestasis. The results of the
      differential diagnosis showed that within 18 items examined only 8 proved to be
      good biliary atresia indicators. They are as follows (in decreasing order):
      ductular proliferation (portal tracts), fibrosis (portal tracts), cholestasis
      (portal tracts), stools colour--acholia, hepatomegaly, canalicular cholestasis
      (lobule), infiltrate (portal tracts), giant cells (lobule). These eight items
      were then gathered in a sole indicator of great discriminative power, with a
      confidence level of 99%. The figures regarding the pathogenesis are: rubella
      virus 0%, herpes simplex virus 0%, listeriosis 0%, cytomegalovirus 2.2%,
      hepatitis B virus 2.4%, toxoplasmosis 2.8%, alpha-1-antitrypsin deficiency 13.1%,
      syphilis 21.1%, autoantibodies against the liver 58.4%. Such work thus revealed
      that those eight most important factors when differentiating biliary atresia from
      neonatal hepatitis remain as fundamental indicators and, when employed alongside
      other diagnostic methods, can help in the assembling of a multifactorial strategy
      less and less invasive and more precise. The pathogenic study, with its heavy
      dependency on time and place, has become more complete with the introduction of
      new diagnostic methods, evolving to the ideal progressive reduction of idiopathic
      processes.

PMID- 10883311
TI  - Squamous cell carcinoma of the esophagus and multiple primary tumors of the upper
      aerodigestive tract.
AB  - Squamous cell carcinoma of the esophagus is frequently associated with other,
      synchronous or metachronous tumors, in the upper aerodigestive tract. All 264
      patients with squamous cell carcinoma of the esophagus, treated in the
      Gastrointestinal Surgery, Esophagus section, of the "Hospital das Clinicas" (Sao
      Paulo University Medical School, Brazil), between 1979 and 1989 were analyzed
      retrospectively with regards to the occurrence of multiple primary tumors in the
      upper aerodigestive tract. Multiple primary tumors were encountered in 10 (3.8%)
      patients. All patients were male and the mean age at the time of the first
      primary was 52.2 years. Tobacco smoke and alcohol were the principal carcinogens
      in these patients (n = 10). The sites of the tumors were: larynx (n = 4), tongue
      (n = 4), lung (n = 2), and oral cavity (n = 1). Two simultaneous, three
      synchronous and five metachronous multiple primary carcinomas were detected. The
      esophagus was the second primary tumor in nine patients. The mean overall
      survival after the diagnosis of the second primary was 2.8 months (SD = 0.89).
      Inquiry regarding other malignancies, associated with panendoscopy should be
      carry out prior to the treatment of the first primary to diagnose simultaneous or
      synchronous primary tumors, and careful follow-up should be performed after
      treatment of the first primary to detect new tumors in these high-risk patients.

PMID- 10883312
TI  - [Importance of esophageal pH monitoring in the screening of gastroesophageal
      reflux in children].
AB  - In the past 20 years the association between gastroesophageal reflux and
      otorhinolaryngological and/or respiratory affections became more evident by many
      studies. At the same time it is known that regurgitation, abdominal pain, growth
      retard, among others signs, could be generated by gastroesophageal reflux in
      infants, and when these signals are present the suspicious must be considered and
      they could be referred to perform pH studies. Sixty children were referred to our
      center to perform pH monitoring with gastroesophageal reflux suspicious, with
      digestive symptoms, respiratory problems or otorhinolaryngological
      manifestations. The patients were divided in two groups: the first, with 25
      children, suffering from digestive manifestations. The second, 35 patients,
      including otorhinolaryngological or pulmonary symptoms. The children with
      digestive manifestations and with otorhinolaryngological or pulmonary symptoms
      were included in the first group. The pH analysis were considered positive for
      reflux when Boix-Ochoa Index (for 8 months of age or less) or DeMeester index
      (for 9 months or more) were above 11.99 or 14.72, respectively. The data were
      also compared to the results of scintigraphic studies for reflux or endoscopic
      findings in 22 patients. The pH monitoring test were positive in 62% patients
      with digestive manifestations. In the group with otorhinolaryngological or
      pulmonary symptoms the positivity was only 29%. In the group of children with
      both affections, the positivity was 66%. In patients that performed scintigraphic
      test or endoscopy, the pH test positivity were similar, 63%, without correlation
      if these other tests were positive or not. Patients with abnormal endoscopy or
      positive scintigraphic tests for gastroesophageal reflux presented 37% of
      positivity in pH test. We conclude that pH monitoring tests could be altered
      mainly when referred to investigate digestive manifestations when compared to
      primary otorhinolaryngological or pulmonary indications. Digestive endoscopy or
      scintigraphic study altered do not mean positive pH test and the inverse
      situation could be find too. Digestive symptoms coexisting with
      otorhinolaryngological or pulmonary afections do not increase the positivity
      frequency of the pH tests when compared with digestive manifestations
      exclusively.

PMID- 10883313
TI  - [Follow-up study of fistula in Crohn's disease].
AB  - Sixteen Crohn's disease patients with fistulae were studied. They had overall 29
      fistulae, 10 treated surgically and 19 with drugs, which were followed regarding
      to the healing and improvement of the process.

PMID- 10883314
TI  - [Effects of partial colonic resection in rats].
AB  - In order to study the effects of partial colectomy, 30 rats Wistar were divided
      into three groups: GI and GII had the cecun and the ileo cecal valve resected and
      proximal colectomy was performed in GI and distal in GII. GIII had distal
      colectomy without cecum resection. The length of the remain colon was of 5 cm in
      all groups. Colostomy was performed in GI, GII and GIII. Parameters evaluated:
      body weight, fecal composition concerning to water, lipids and proteins on
      preoperative time and on the 10th, 20th, 30th, 40th, 50th and 60th days of
      postoperative time. All statistical tests were conducted at a 5% two-sided risk
      level. The evaluation was made by analysis of variance techniques. CONCLUSIONS:
      Concerning to body weight, there is no significant difference on the late
      postoperative time in any group or when comparing the three groups on this same
      period. On late postoperative time, GI and GII had a large amount of fecal water,
      lipids and proteins when compared to the preoperative time and to GIII. On the
      60th day there's no significant difference on the quantity of fecal water when
      comparing the three groups and the same occurs on the 50th day when considering
      the quantity of fecal proteins.

PMID- 10883315
TI  - Enhancement of sodium intestinal secretion in relation to absorption in
      malnourished rats. Hyperosmolar challenge.
AB  - Two experimental models were tried in young malnourished rats in order to study
      effect of an hyperosmolar challenge in the small intestine on the bi-directional
      fluxes of sodium. Weanling rats were fed with energy restricted diets. In model I
      1 mL of NaCl 900 mOsm/kg was introduced in the small intestine of the rats and
      left from 5 up to 70 min, in order to determine the moment of higher net Na+
      secretion, which occurred at 10 min. In model II, the bi-directional fluxes of
      Na+ and Cl- were studied using NaCl or mannitol 900 mOsm/kg under the effect of
      mecholil, atropine or 2-4 dinitrophenol, for 10 min. Mecholil decreased the Na+
      absorption enhancing the net secretion. Control rats were used as reference. In
      the restricted diets animals occurred an increase of the net secretion stimulated
      by NaCl 900 mOsm/kg, and this effect was enhanced by mecholil. It is suggested
      that in malnutrition there is an impairment in Na- intestinal absorption.

PMID- 10883316
TI  - [Mechanisms of absorption of amino acids and oligopeptides. Control and
      implications in human diet therapy].
AB  - The mechanisms involved in the absorption of amino acids and oligopeptides are
      reviewed regarding their implications in human feedings. Brush border and
      basolateral membranes are crossed by amino acids and di-tripeptides by passive
      (facilitated or simple diffusion) or active (Na+ or H+ co-transporters) pathways.
      Active Na(+)-dependent system occurs mainly at brush border and simple diffusion
      at basolateral, both membranes have the passive facilitated transport. Free-amino
      acids use either passive or active transport systems whereas di-tripeptides do
      mainly active (H+ co-transporter). Brush border have distinctive transport system
      for amino acids and di-tripeptides. The former occurs mainly by active Na+
      dependently whereas the later is active H(+)-dependent with little affinity for
      tetra or higher peptides. Free amino acids are transported at different speed by
      saturable, competitive carriers with specificity for basic, acidic or neutral
      amino acids. Di and tripeptides have at least two carriers both electrogenic and
      H(+)-dependent. The basolateral membrane transport of amino acids is mostly by
      facilitated diffusion while for di-tripeptides it is an active anion exchange
      associated process. The main regulation of amino acids and di-tripeptide
      transport is the presence o substrate at the mucosal membrane with higher the
      substrate higher the absorption. Di and tripeptides are more efficiently absorbed
      than free amino acids which in turns are better absorbed than oligopeptides. So
      di-tripeptides result in better N-retention and is particularly useful in cases
      of lower intestinal absorption capacity. The non-absorbed peptides are digested
      and fermented by colonic bacteria resulting short-chain fatty acids, dicarboxylic
      acids, phenolic compounds and ammonia. Short-chain fatty acid provides energy for
      colonocytes and bacteria and the ammonia not fixed by bacteria returns to the
      liver for ureagenesis.

PMID- 10883317
TI  - [Treatment of unspecific ulcerative rectocolitis in a child with enemas
      containing butyrate. Case report].
AB  - OBJECTIVE: To report a promising therapy to ulcerative colitis in children.
      METHODS: We report a case of ulcerative colitis in 4 years old female, who had
      this diagnosis since she was 1 year old. The treatment of RCU1 had an
      unsatisfactory response to conventional therapies (rectal and oral
      corticosteroids and immunosuppressive agent). RESULTS: She showed improvement,
      using enemas containing butyrate, in clinical, endoscopic and histological
      parameters. CONCLUSIONS: Although the role of butyrate in the treatment of
      ulcerative colitis still remains to be determined, we find effective response in
      this case. Despite evidences that butyrate may be beneficial and safety in
      treating refractory distal ulcerative colitis, results of controlled trials,
      specially in children will be necessary to prove the efficacy of this therapy.

PMID- 10883318
TI  - [Celiac disease: evolution in knowledge since its original centennial description
      up to the present day].
AB  - In the recent past, some celiac disease features have been discussed in
      literature specially related to genetic susceptibility, pathogenesis, clinical
      presentation and diagnostic criteria. Immunological abnormalities characteristic
      of celiac disease, such as circulating antibodies and increased numbers of intra
      epithelial lymphocytes containing a high percentage of gamma-delta T cells have
      been demonstrated. Other pictures of clinical presentation besides the classical
      one deserve attention namely short stature, iron-resistant anaemia, enamel
      hypoplasia, constipation, neurological manifestation and osteoporosis, among
      others. Asymptomatic presentation has been recognized since development of
      serological markers such as anti-gliadin, anti-reticulin and anti-endomysium
      antibodies. Up to now, small intestinal biopsy is the only decisive diagnostic
      approach. A Federal law has recently imposed food manufactures to place labels
      informing the presence of gluten in industrialized foods in Brazil. Lately there
      has been an increase in celiac disease patients registered in the Brazilian
      Celiac Association.

PMID- 10883319
TI  - [Serum antibodies in celiac disease].
AB  - Accurate diagnosis of celiac disease is important because patients are advised to
      adhere to a strict gluten-free diet for life. This management is critical to
      avoid disease complications such as malignancies. In this review the new
      terminology for the disease clinical features (active, silent, latent and
      potential celiac disease) and the disease association with other conditions are
      commented. The value and efficacy of the assessment of serum antigliadin
      antibodies and of antireticulin, antiendomysial and tissue transglutaminase
      autoantibodies in the diagnosis and follow-up of the celiac disease are
      particularly evaluated.

PMID- 10883320
TI  - Vasopressin and bradykinin receptors in the kidney: implications for tubular
      function.
AB  - Vasopressin and bradykinin are two of the most important peptides in regulating
      vascular tone, water, and ionic balance in the body, and thus they play a key
      role in controlling blood pressure. In addition to being a potent
      vasoconstrictor, Vasopressin also has an antidiuretic activity in the kidney,
      whereas kinins regulate renal blood flow in addition to their vasodilatory and
      natriuretic activity. We review here the primary evidence for the localization of
      the vasopressin and kinin receptors and their role in ionic and water regulation
      in the kidney.

PMID- 10883321
TI  - Ethanol effect on the chick embryo ossification: a macroscopic and microscopic
      study.
AB  - This study attempts to analyze anomalies in avian embryos induced macroscopically
      and microscopically when exposed to ethanol (EtOH) during the first stages of
      development. Fertilized chicken eggs were employed in this study. The eggs were
      incubated at 37.8 degrees C. Some of the eggs were treated on day 0 with EtOH
      (20%, 40% and 60%) by instillation in the air sac. The control group was
      instilled with 0.1 ml of NaCl at 0.9%. Other eggs were treated on the 4th post
      incubation day, employing the same methodology. The embryos in both groups were
      removed from the eggs on the 11th incubation day and examined using a dissecting
      binocular microscope. After macroscopic analysis, the samples obtained were fixed
      in 10% formol, photographed and processed according to common histological
      techniques and the Picrosirius method. Embryos treated with EtOH demonstrated a
      significant weight decrease. Microscopic analysis by means of the Picrosirius
      method revealed that the intra-membranous ossification process presents less
      development, and therefore there was less type I collagen in trabecular bone in
      the embryos post-exposure to EtOH with respect to the control.

PMID- 10883322
TI  - The superior colliculus, a neuronal network resistant to the Gaba withdrawal
      syndrome.
AB  - Chronic intracortical perfusion of GABA (Gamma Amino Butyric Acid) and its
      subsequent withdrawal generates the GABA withdrawal syndrome (GWS). This
      particular epileptic model has been observed in the motor cortex of monkeys and
      rats. Our purpose was to study the GWS in the motor cortex (MC), dorsal
      hippocampus (DH), and superior colliculus (SC). Thirty chronically-implanted
      adult Wistar rats were separated into 3 groups of 10 (8 experimental and 2
      controls). The first group received GABA in MC, the second in the DH and the
      third in the SC. GABA was released in doses of 10 to 60 micrograms/microliter/h
      for 6 days employing osmotic mini-pumps. Two control rats per group received
      saline solution in the above-mentioned structures. Rats perfused in the MC showed
      GWS after interruption of the GABA flow. The group perfused in the DH showed
      paroxysmal discharges and epileptic seizures during perfusion. They also later
      showed GWS. No epileptic effects were observed in the SC-perfused group during
      either the GABA perfusion or during withdrawal. None of the six control animals
      showed epileptic effects. Our results show that the SC offers a strong resistance
      to GWS. This could be explained by the particular neuronal network structure of
      rat SC.

PMID- 10883323
TI  - A model of internal control may improve the response time of an automatic
      arterial pressure controller.
AB  - A simplified model for the arterial pressure control system was implemented on a
      personal computer using Matlab Simulink. Model responses to variations of
      systemic vascular resistance were comparable to those predicted by physiology.
      Computer simulation suggested that including this model of the internal pressure
      control system within the design of an external controller would achieve better
      arterial pressure control and faster response than previous systems.

PMID- 10883324
TI  - Anti-inflammatory activity of Urera baccifera (Urticaceae) in Sprague-Dawley
      rats.
AB  - On a preliminary test, anti-inflammatory and analgesic dose-related activities on
      rats were observed for the aqueous fraction of Urera baccifera; this extract was
      bioassay-guided fractionated and the final aqueous fraction was used according
      the ethnobotanical use. Carrageenan-induced edema (n = 6), was used as an assay
      in the fractionating process. The anti-inflammatory and antinociceptive
      properties of the final aqueous fraction were studied using in vivo models. For
      the anti-inflammatory activity rat paw edema (n = 6), pleurisy induced by
      carrageenan (n = 6) and ear edema induced by topical croton oil (n = 6) models
      were used, and tail-flick test (n = 6), abdominal constrictions induced by acetic
      acid (n = 6), and formalin test (n = 6), were used for the antinociceptive
      activity. The tests performed showed an inhibition effect on leukocyte migration,
      and a reduction on pleural exudate, as well as dose-dependant peripheral
      analgesic activity, at a range of 25-100 mg/kg i.p. The final aqueous fraction
      contains most of the anti-inflammatory activity of the plant U. baccifera. A
      possible mechanism of action is discussed and based on the results we conclude
      that this plant has a potential for both anti-inflammatory and analgesic activity
      at the clinical level.

PMID- 10883325
TI  - Essential oil of Lepechinia schiedeana (Lamiaceae) from Costa Rica.
AB  - The composition of the essential oil isolated by steam distillation from aerial
      parts of the Costa Rican herb Lepechinia schiedeana (Schlecht) Vatke (Lamiaceae)
      collected in El Empalme, Costa Rica, was determined by capillary gas
      chromatography (GC) and coupled gas chromatography-mass spectrometry (GC-MS)
      analyses. Fifty-one components were identified corresponding ca. 93% of the oil.
      The major components were beta-pinene (26.6%), cis-pinocamphone (25.1%), delta-3
      carene (6.1%), trans-pinocamphone (4.0%), camphor (3.8%) and beta-caryophyllene
      (3.7%).

PMID- 10883326
TI  - [Cyanobacteria as indicators of organic contamination].
AB  - In two Costa Rican rivers used as receptors for domestic sewage, treated by
      primary stabilization ponds, were taken a total of 28 samplings located at the
      pond exit and at three different sites in each river: 100 m before the ponds
      discharge, at the discharge and 100 m after the discharge. These sampling were
      done for a five and a half years including dry and rainy seasons. In each
      sampling site, samples were collected of five different substrates: stones,
      submerge and semi submerge vegetation, tree trunks or sticks, water and
      artificial substrates. For each sample were used two types of artificial
      cultures, WC and BG110. A total of 55 cyanobacteria species isolations were
      obtained, belonging to a 26 genera, between these the most common were Phormidium
      with nine species, Microcystis with five species, Leptolyngbya and Pseudanabaena
      with four species each and Oscillatoria with three species. More cyanobacteria
      species were isolated in water substrate and less isolations in tree trunks and
      submerge vegetation. Konvophoron, Cyanarcus and Pilgeria only were isolate from
      water samples inoculated in culture media WC and in few opportunities, while
      three Leptolyngbya species and four Phormidium species were isolated very often.
      At the stabilization ponds Phormidium sp4 was dominant in 25 of 28 sampling while
      in the last others were the chlorophycea I. In this study were observed an
      increase in the frequency of cyanobacteria at the higher contamination places,
      and a species substitution between different sampling points. There were no
      biomass studies, therefore is not possible to relate between different
      cyanobacteria species and some specific types of water quality.

PMID- 10883327
TI  - [Non detection of enterovirus in the bivalve Anadara tuberculosa
      (Bivalvia:Arcidae) caused by chemical contamination in the Pacific of Costa
      Rica].
AB  - Anadara tuberculosa is one of the most abundant mollusks of commercial importance
      in Costa Rica. Its habitat water is a potential source of fecal and chemical
      contamination to humans. We wanted to asses enterovirus, mainly poliovirus and
      hepatitis A virus and chemicals such as sulphates and nitrates in meat and body
      fluids. Thirteen samples were taken from four sites in Nicoya Gulf, three sites
      in the Sierpe-Terraba mangrove (Pacific of Costa Rica) and from five fish markets
      in San Jose, the capital of Costa Rica. Samples were tested for 1) fecal
      coliforms (Most Probable Number/100 ml), 2) isolation of enterovirus in cell
      culture (Hep-2, FrhK-4), 3) cell cytotoxicity in Vero cells and 4) the ability to
      inactivate 10 ID50% of poliovirus in cell culture. The Most Probable Number/100
      ml in surrounding water was higher than the accepted standard for recreational
      waters, although the number of fecal coliforms in meats and body fluids was lower
      than in the external water. No cytopathogenic agents were isolated, but we found
      nitrate and sulphate concentrations that exceeded maxima for human consumption
      and recreation. The intrinsic cytotoxicity of the samples was at a 1/8 dilution,
      but some samples were cytotoxic at dilutions of 1/128. Body fluids were more
      cytotoxic than meats, but a positive correlation between cytotoxicity and
      chemical contamination was not determined: apparently other pollutants not
      identified in this study were responsible. Fluid and meat capacity to inactivate
      10 ID50% of poliovirus in cell culture was demonstrated. Samples that were toxic
      for cell cultures also showed a higher percentage of poliovirus inactivation.
      Monitoring chemical pollution in these waters is highly recommended.

PMID- 10883328
TI  - Infection of white rat peritoneal macrophages with Toxoplasma gondii, (Coccidia:
      Sarcocystidae) after Trypanosoma lewisi (Kinetoplastida: Trypanosomatidae)
      infection.
AB  - Peritoneal macrophages from Wistar rats, inoculated and non-inoculated with 10(6)
      T. lewisi trypomastigotes, were cultured and infected with 10(6) T. gondii
      tachyzoites. Multiplication rates of this parasite were studied after 1, 24 and
      48 h of infection but there were not significant differences between the number
      of parasites found inside of macrophages coming, either from T. lewisi infected
      or non infected rats. On the other hand, in vivo studies of Toxoplasma
      multiplication inside peritoneal macrophages, showed that there is an increase of
      parasite number in cells from T. lewisi infected rats, as compared with those
      macrophages from non infected rats. This effect was statistically significant and
      was more evident after four days of infection. Therefore, it has been
      demonstrated that in vivo, but not in vitro T. lewisi infections, causes an
      important decrease of the natural resistance to T. gondii of the white rats,
      which is manifested by the major invasion and multiplication of the parasite
      inside of peritoneal macrophages.

PMID- 10883329
TI  - [Neutralization of the hemorrhagic effect induced by Bothrops asper (Serpentes:
      Viperidae) venom with tropical plant extracts].
AB  - Organic extracts representing 48 species included in 30 families of Costa Rican
      tropical plants were evaluated for their ability to neutralize hemorrhagic
      activity induced by the venom of the snake Bothrops asper. A bioassay in mice was
      used, based on intradermal injection of either venom or venom-extract mixtures
      followed by the measurement of hemorrhagic areas. Total inhibition of hemorrhage
      was observed with the ethanolic, ethyl acetate and aqueous extracts of Bursera
      simaruba, Clusia torresii, C. palmana, Croton draco, Persea americana, Phoebe
      brenesii, Pimenta dioica, Sapindus saponaria, Smilax cuculmeca and Virola
      koschnyi. Chemical analysis of these extracts identified catequines, flavones,
      anthocyanines and condensated tannins, which may be responsible for the
      inhibitory effect observed, probably owing to the chelation of the zinc required
      for the catalytic activity of venom's hemorrhagic metalloproteinases.

PMID- 10883330
TI  - Cystine nephrolithiasis in an endangered canid, Chrysocyon brachyurus (Carnivora:
      Canidae).

PMID- 10883331
TI  - Outcome from complex neurosurgery: an evidence based approach.
AB  - BACKGROUND: The aim of this study was to determine outcome, including quality of
      life, after surgery for petroclival meningioma using a standard skull base
      approach and to carry out an evidence based appraisal of the relevant literature.
      METHOD: Pre- and post-operative data including adverse events were prospectively
      recorded in 19 patients (15 females, age range 29-63) undergoing a transpetrous
      approach for a petroclival meningioma. Patients were assessed using the GOS and
      SF-36 post operatively. FINDINGS: 24 operations were done. 6 patients developed a
      new permanent neurological deficit and 10 experienced a temporary deficit or
      exacerbation of existing deficits. At 1 year 15 patients had made a good/moderate
      recovery, 3 were severely disabled and 1 died--in keeping with other studies. By
      contrast the SF-36 showed that in all 8 categories of the SF-36 between 39-72% of
      surviving patients were functioning below the accepted norms. INTERPRETATION:
      After transpetrous excision of a petroclival meningioma the quality of life for
      the patient is worse than that indicated in surgeons' reported results. This
      paper represents an attempt to address the issue of evidence-based medicine and
      finds that such an approach is not apparent in the medical literature on this
      pathology. While we argue that methods for measuring outcome should be refined
      and carers input recognised it does raise certain philosophical considerations.
      It is the counsel of perfection and if achieved may lead to surgeons operating on
      fewer patients, more petroclival cases being viewed as inoperable because of the
      higher morbidity, despite there being an inescapable pathway to surgical
      intervention.

PMID- 10883332
TI  - Age and outcome after severe head injury.
AB  - The authors analyzed the relationship between patient age and the final outcome
      in a series of 810 patients aged 14 years or older who were consecutively
      admitted between 1987 and 1996 after suffering a severe closed head injury. The
      most relevant clinico-radiological variables were prospectively collected in a
      Data Bank. Stratified and logistic regression analyses were performed in order to
      assess the influence of age on adverse outcome and the interaction between
      patient age and other prognostic indicators. Our results reaffirm that the
      adverse outcome rate increases steadily with age in severe head injured patients
      and that age effect on outcome is independent of other prognostic variables. The
      odds of having an adverse outcome increases significantly over 35 years of age
      being 10 times higher in patients older than 65 years as compared to those aged
      15-25 years (reference age group). The adverse influence of an advanced age on
      the final outcome has not yet been satisfactorily explained but an older brain
      may have an impaired ability to recover after a pathological insult as compared
      to a younger one.

PMID- 10883333
TI  - Cytoarchitectonic basis for safe entry into the brainstem.
AB  - This work is a continuation of the anatomical study in which safe approach zones
      through the floor of the fourth ventricle--infrafacial and suprafacial--were
      morphologically and morphometrically defined (Acta Neurochir (1997) 139: 1014
      1019). The purpose of cytoarchitectonic study was to analyze correlation between
      morphometry of the facial colliculus and hypoglossal triangle and localization of
      the corresponding cranial nerves nuclei in the brainstem tegmentum in order to
      verify morphometrical borders of the previously defined zones. Morphometrical
      evaluation of the fourth ventricle floor of 10 examined brainstems was initially
      performed. Distances from obex to the rostral portion of hypoglossal triangle and
      facial colliculus were determined. Then a series of axial sections of each
      specimen, stained for Nissl substance, were analyzed to define the distance from
      obex to the rostral portion of the hypoglossal and abducens nuclei. Distances of
      motor trigeminal and facial nuclei from the midline sagittal plane were also
      measured. The obtained results allowed morphometrical determination of the infra
      abducental and supra-abducental region of safe entry into the brainstem
      tegmentum. Infra-abducental region corresponds to infrafacial safe approach zone
      and supra-abducental to suprafacial zone. The distance of the rostral portion of
      facial colliculus from obex was longer than the distance of the rostral pole of
      abducens nucleus from obex in every examined specimen (by 0.7 mm on average). A
      very similar correlation between the distance of the rostral margin of
      hypoglossal triangle and localization of the rostral pole of hypoglossal nucleus
      was found. The rostral portion of hypoglossal triangle was longer by 1.5 mm on
      average. The obtained results show that previously defined infrafacial and
      suprafacial safe approach zones via the fourth ventricle floor correspond
      morphometrically to tegmental regions of safe entry--infra-abducental and supra
      abducental respectively. It suggests that morphometrical evaluation of the fourth
      ventricle floor proposed by the authors could be useful in the intra-operative
      determination of safe entry via the rhomboid fossa into the brainstem tegmentum.

PMID- 10883334
TI  - Interstitial irradiation for craniopharyngioma.
AB  - The results of interstitial irradiation treatment for craniopharyngioma in two
      patients with six year follow-ups are presented. Stereotactic interstitial
      irradiation with Iodine-125 sources as sole therapy was employed in two adult
      patients who refused surgical resection. The diagnoses were confirmed by
      stereotactic biopsy. The first tumour which underwent interstitial irradiation
      was solid and 4 cm in diameter, and the second, 2.7 cm in diameter, had both
      cystic and solid components. The implanted Iodine-125 seeds delivered 67 Gy and
      60 Gy to tumour periphery at the rate of 12 and 14 cGy/h, respectively, were
      removed at the end of designated radiation periods. Tumour shrinkage and central
      hypodensity, first observed 3 months after irradiation, continued until one
      tumour shrank to less than 1 cm at 12 months, and the other disappeared
      completely at 24 months. In both cases functional integrity was restored, and
      neither radiation induced toxicity nor recurrence has occurred six years after
      treatment. The results in these two cases suggest that solid craniopharyngiomas
      are sensitive to interstitial irradiation.

PMID- 10883335
TI  - Transsphenoidal cephaloceles in adults. A report of two cases and review of the
      literature.
AB  - Transsphenoidal cephalocele rarely occurs in adults. We describe two adult cases
      with transsphenoidal cephaloceles. The first case was a 53-year-old female who
      presented with spontaneous cerebrospinal fluid (CSF) rhinorrhea. Magnetic
      resonance (MR) imaging demonstrated a transsphenoidal meningocele. Surgical
      repair was attempted via the transsphenoidal route. Rhinorrhea recurred at one
      month and also two years later. Transsphenoidal surgical repairs were repeated.
      There has been no evidence of CSF leakage in the four years of follow-up after
      the last surgery. Transsphenoidal repair seems to be the most suitable approach
      in this case. The second case was a 26-year-old female with secondary amenorrhea,
      diabetes insipidus, bitemporal hemianopsia, and see-saw nystagmus. MR imaging
      demonstrated a transsphenoidal encephalocele with the optic chiasma and
      infundibular recesses descending into the meningocele and an agenesis of the
      corpus callosum. The first operation was performed via the transnasal route and
      the second by sublabial transmaxillary transsphenoidal approach six months later.
      Postoperative MR imaging revealed reduction of the encephalocele. There was
      neither worsening nor noticeable improvement in the neurological or
      endocrinological function. However, in this type, complete repair is often
      impossible, and non-radical surgery such as transsphenoidal repair may be
      indicated as most suitable. They should be selected with careful assessment
      referring to MR findings and clinical symptoms and signs.

PMID- 10883336
TI  - Intracranial pressure processing with artificial neural networks: prediction of
      ICP trends.
AB  - It is well known that intracranial pressure (ICP) is influenced by an array of
      predictable and unpredictable factors, which gives rise to a signal heavily
      loaded with stochastic, i.e. random components. Hence, statistical modelling of
      this signal has proved to be of limited utility, in spite of the very
      sophisticated mathematical methods applied. In recent years, neural network
      algorithms (ANN), which are an alternative to statistical methods, have proved
      their effectiveness in the prediction of trends, as applied in a variety of
      medical and non-medical tasks. We therefore attempted to test the efficiency of
      neural models in the on-line prediction of ICP values, compare their
      effectiveness to statistically oriented algorithms and combine ANN methods with
      some newer signal processing algorithms, like wavelet decomposition. Prediction
      horizons of up to 5 minutes have been tested with various architectures of the
      neural predictor. For a 3 minute prediction horizon, a satisfactory accuracy of
      forecasting has been achieved with "plain" ANN, as expressed by the "average
      relative variance coefficient". This was measured by the ratio of the prediction
      error obtained, in relation to the error which would occur if a current value
      were taken as the forecasted one. The prediction quality with statistical
      autoregressive models has proved unsatisfactory, whilst the result obtained using
      the ANN model with the wavelet transform incorporated, performed significantly
      better than the ANN models alone. The prediction quality obtained with the ANN
      methodology seems to be satisfactory over a short time horizon, though no
      conclusion can be derived at this stage of the study, as to the clinical utility
      of this method. In particular, even with this methodology, it is not possible to
      forecast any sudden dehiscencies of the ICP signal with any practical
      reliability. From the point of view of modelling theory, such sharp deviations of
      the signal may be regarded as a "catastrophe". This implies the necessity for a
      different approach to the ICP signal analysis with the artificial intelligence
      methodology; one, that is more oriented towards the global properties of the
      signal.

PMID- 10883337
TI  - Intracranial pressure processing with artificial neural networks: classification
      of signal properties.
AB  - Intracranial pressure (ICP) is commonly used by neurosurgeons as a source of
      valuable information about the current condition of the neurosurgical patient.
      Nevertheless, despite years of effort, extracting clinically valuable information
      from the ICP signal is still problematical. Approaches, using current values of
      ICP, may fail to disclose imminent risk, because unpredictable factors can
      rapidly change the properties of the signal. An alternative approach is to
      determine some global characteristics of the signal within a longer time interval
      and such statistical analyses have been proposed by several authors. A further,
      rarely considered, problem is assessment of the results obtained from the point
      of view of their practical utility and/or such classification of the obtained
      properties of the signal that they correspond to certain clinical states of the
      patient. While this might be a typical task for discriminant analysis, we
      approached the analysis using an alternative methodology, that of computational
      intelligence, implemented in artificial neural networks (ANN). We tested two
      variants of the ANN algorithms for classification and discrimination of global
      properties of the ICP signal. In a "dynamic pattern classification" the network
      was presented with several sections of ICP records together with information from
      the expert-neurosurgeon, classifying 4 risk groups. In this mode no data pre
      processing was carried out, in contrast to our second approach, in which the
      signal had been pre-processed using published statistical analyses and only these
      intermediate coefficients were fed into the ANN classifier. The results obtained
      with both classification methods at their current stage of training were similar
      and approximated to a 70% rate of judgements consistent with the expert scoring.
      Nevertheless, the method based on the assessment of global parameters from the
      ICP record looks more promising, because it leaves the possibility for
      modification of the set of parameters analysed. The new parameters may include
      information extracted not only from the ICP signal, but also from other
      diagnostic modalities, like colour coded Doppler ultrasonography. The ultimate
      goal of this work is to build up a pseudo-intelligent computer expert system,
      which would be able to reason from a reduced set of input information, available
      from a standard monitoring modality, because it had been taught salient links
      between these data and higher-order data, upon which expert scoring was based.

PMID- 10883338
TI  - Correlation between magnetic resonance images and draining patterns in dural
      arteriovenous fistulas with leptomeningeal venous drainage.
AB  - OBJECTIVE: To compare abnormal intensity areas on intracranial magnetic resonance
      images (MRI) and the pattern of venous drainage in dural arteriovenous fistulas
      (DAVFs) with retrograde venous drainage. METHODS: Thirteen patients with
      retrograde venous drainage of DAVFs were divided into two groups based on the
      venous drainage pattern determined by detailed angiographic and MRI study. In
      group 1 there was an accessory route draining into another sinus besides the main
      draining sinus. In group 2 no such accessory route was present. RESULTS: In group
      1 patients (n = 8), MRI detected no unusual intensity areas; 5 patients in this
      group had episodes of bleeding. Angiographically, in this group retrograde venous
      drainage tended to occur via multiple varices. On the other hand, none of the 5
      group 2 patients experienced a bleeding episode. Angiographically, there was a
      low incidence of varices. On T2-weighted images, these patients had a
      hyperintensity area. Following treatment, these areas of abnormality disappeared
      on T2-weighted MRI. CONCLUSION: Among 13 patients with DAVFs which drained
      retrogradely, those with a variceal accessory route (Group 1, n = 8) had a higher
      incidence of haemorrhage. In patients without such an accessory route (Group 2, n
      = 5) abnormal signal intensity on MRI was indicative of venous congestion.
      Continuous-mode angiography and MRI study were useful in the precise
      identification of DAVFs with a venous drainage route.

PMID- 10883339
TI  - Steno-occlusive changes in the external carotid system in moyamoya disease.
AB  - To evaluate the steno-occlusive changes in the external carotid system in
      moyamoya disease, cerebral angiograms of 39 moyamoya patients were
      retrospectively reviewed. There were 26 females and 13 males, age ranged from 4
      to 62 years with a mean of 26 years. Initial symptoms were ischaemia in 27
      patients, haemorrhage in 9, and none in 3. Stenosis, occlusion, and dilatation in
      the external carotid system were analysed angiographically. No stenosis or
      occlusion of the superficial temporal artery, middle meningeal artery, or
      occipital artery was observed in either preoperative or postoperative follow-up
      angiograms in any patients. Steno-occlusive changes do not occur in the external
      carotid system, but are confined in the internal carotid system in moyamoya
      disease.

PMID- 10883340
TI  - Rationale for interbody fusion with threaded titanium cages at cervical and
      lumbar levels. Results on 357 cases.
AB  - STUDY DESIGN: Retrospective analysis of 357 cases of degenerative disc disease
      treated by interbody fusion with threaded titanium cages. OBJECTIVE: To determine
      the safety and efficiency of cervical and lumbar interbody fusions using threaded
      titanium cages and autogenous bone. SUMMARY OF BACKGROUND DATA: Stabilizing the
      anterior column by interbody fusion, though reported over 50 years ago, is less
      commonly done than posterior fusions. The recent development of rigid cages
      housing autogenous bone simplifies the technique of interbody fusion. This report
      shows our combined results using this technique. MATERIALS AND METHODS: One
      hundred thirty-five patients had cervical fusions at 175 levels between C3 and
      C7. Two hundred twenty-two patients had lumbar fusion at 243 levels between L2
      and S1. All surgeries involved one or two disc spaces except for one three level
      cervical fusion. We implanted all disc spaces with threaded cages containing
      autogenous bone. RESULTS: In the cervical area, 95% of the radiculopathic
      patients had a good to excellent result, but only 50% of the myelopathic patients
      did so. At lumbar level, 80% of the patients were classified as good to
      excellent, 15% improved but remained disabled, 5% had minimal or no improvement.
      The cervical fusion rate was 90% at 6 months and 100% at one year. Lumbar fusion
      rate was 91% at one year and 96% at 2 years. No late breakage or cage
      displacement occurred. CONCLUSIONS: Cervical and lumbar interbody fusions with
      threaded titanium cages appear to be efficacious with few complications. Long
      term follow-up (4 years cervical, 7 years lumbar) confirms that impression.

PMID- 10883341
TI  - Brain abscess formation in radiation necrosis of the temporal lobe following
      radiation therapy for nasopharyngeal carcinoma.
AB  - BACKGROUND: Radiation necrosis is a known complication following radiation
      therapy for extracranial as well as intracranial tumours. However, brain abscess
      formation in radiation necrosis has not been reported in the literature. We
      report the clinical data of 6 patients suffering from this condition. METHOD:
      Twenty-eight patients with radiation necrosis of the temporal lobe following
      radiotherapy for nasopharyngeal carcinoma were treated surgically at the
      Department of Neurosurgery, Queen Elizabeth Hospital, Hong Kong between January
      1992 and July 1999. Of these, 6 cases were complicated by brain abscess
      formation. The clinical data of these 6 patients are retrospectively reviewed.
      FINDINGS: The patients were 5 males and 1 female, ranging in age from 41 to 67
      years. Three patients had previous treatment with steroids for the symptomatic
      radiation necrosis. A history of nasal infection or otitis media was recognised
      in all 6 patients. All patients were treated surgically by temporal lobectomy and
      excision of the necrotic tissue together with the abscess cavity. Intra
      operatively, a bony defect was observed between the middle cranial fossa and the
      sphenoid sinus in 3 patients and the bony defect was repaired with a temporalis
      muscle flap. The species of organisms could only be identified in 3 patients. In
      3 patients, the pus smear was positive but the culture was negative.
      Subsequently, 4 patients recovered and 2 patients died. INTERPRETATION: Cerebral
      radiation necrosis is a predisposing cause of brain abscess formation. Surgical
      excision is recommended as the treatment of choice in this group of patients.

PMID- 10883342
TI  - A new procedure for frameless computer navigated stereotaxy.
AB  - OBJECTIVE: Stereotactic procedures using frame-based systems have become well
      established in neurosurgery. Later, stereotactic computers have provided the
      neurosurgeon with a broader range of applications. A new, frameless stereotactic
      guide which utilizes the navigational abilities of a computer has been developed.
      This clinical study evaluates the accuracy and safety of the system when applied
      for puncture of tumours and abscesses in the cerebrum. METHODS: Using a frameless
      setup 36 patients were operated on for a total of 39 intracranial processes over
      a period of two years. Three patients were operated on twice. Computer data, time
      of surgery, anesthesia, complications, tumour localization and tissue
      examinations were recorded. RESULTS: Biopsies were obtained from all lobes of the
      cerebrum and a diagnosis established in all cases except two. Mean age and total
      range was 52 years and 15-82 years, respectively. Median time of surgery was
      approximately 60 minutes including positioning of the patient and the
      registration process on the stereotactic computer. Local anesthesia was used for
      25 operations and general anesthesia for 14 operations. There was one
      postoperative abscess formation in a previously immunosuppressed patient and a
      per-operative epileptic seizure caused by electrocoagulation of the dura in a
      second patient. CONCLUSIONS: Based on this clinical study a new procedure for
      obtaining stereotactic biopsies of intracranial processes is introduced. All
      tumours were successfully reached with two cases of complications.

PMID- 10883343
TI  - Mechanical accuracy of a new stereotactic guide.
AB  - OBJECTIVE: A new stereotactic guide using a navigational computer is developed
      for stereotactic procedures. In order to compare the mechanical accuracy of the
      guide to frame based systems, an error analysis study was designed. METHODS: A
      biopsy procedure was simulated using a phantom model. Targets with known co
      ordinates in a three-dimensional Cartesian co-ordinate system were positioned
      inside the skull model. A biopsy needle was inserted along computer set
      trajectories from three different entry points. The position of the biopsy needle
      in the co-ordinate system was measured. Distance from needle tip to target was
      calculated and defined as the error of the system for each trial. The results
      were statistically analyzed for precision and biasedness. RESULTS: A total of 242
      accuracy measurements (182 on two MRI scans, 60 on one CT scan) were carried out.
      Mean incision length along the trajectories was 59 mm. Mean error using MRI scans
      was 3.8 mm and for the CT scan 2.9 mm. The error of the stereotactic computer was
      found to be 1.0 mm with both MR and CT imaging. The main cause of error for the
      MRI based trials was distortion of the magnetic field. CONCLUSION: The results
      indicate a stereotactic system with high degree of accuracy. This is confirmed by
      a clinical study of 39 biopsies where all tumours were reached. MRI affected the
      mechanical accuracy significantly due to distortion of the magnetic field. The
      accuracy is comparable to other studies performed on both stereotactic computers
      and frame based systems.

PMID- 10883344
TI  - Systemic administration of mexiletine for attenuation of cerebral vasospasm
      following experimental subarachnoid haemorrhage.
AB  - Mexiletine is a class Ib drug that is widely used to treat ventricular
      arrhythmias. This compound is mainly known as a sodium channel blocker, but
      studies have demonstrated that it can also activate ATP-sensitive K+ channels and
      block Ca2+ channels. Recent in vitro data from experiments on liposomes indicate
      that mexiletine is also a potent antioxidant. The unique activity profile of this
      drug raised the possibility that it might be of benefit in limiting cerebral
      vasospasm. Our first series of experiments assessed the effects of mexiletine on
      transclivally exposed rabbit basilar arteries. The arteries were treated with 50
      mM KCl, 20-nM endothelin-1 (ET-1), or 100-microM lysophosphatidic acid (LPA) in
      the presence or absence of 400-mM mexiletine. Vasoconstriction caused by KCl, ET
      1, and LPA was inhibited by mexiletine. In a second series of experiments,
      subarachnoid haemorrhage (SAH) was induced in rabbits by injecting 3-ml of
      autologous arterial blood into the cisterna magna. Forty-eight hours after SAH
      induction, transclivally exposed basilar arteries exhibited a spastic
      constriction that was partially reversed by topical application of 400-microM
      mexiletine. In a third set of experiments, mexiletine was administered orally at
      dosages of 80-, 20, and 5-mg/kg/day t.i.d., beginning 3 hours before SAH to study
      the prevention of vasospasm. In a separate group of animals, 80- and 20-mg/kg/day
      t.i.d. of mexiletine was administered 21 hours post-SAH induction, to study the
      reversal of vasoconstriction. Microscopic analysis of vessels from controls (no
      SAH), SAH-only, and SAH + mexiletine groups indicated there was 71.43% vascular
      constriction in the SAH-only group compared with controls. Considerable
      vasorelaxation was seen in the prevention study, in which average arterial cross
      sectional areas were reduced by only 17.86% and 39.29% in the mexiletine 80- and
      20-mg/kg/day groups, respectively, compared with controls (p < 0.001). Compared
      with controls, average arterial cross-sectional areas were reduced by 53.58% and
      64.29% in the mexiletine 80- and 20-mg/kg/day reversal groups, respectively. Our
      findings indicate that mexiletine induces potent relaxation in cerebrovascular
      arteries contracted with various agents, and that it prevents and partially
      reverses SAH-induced vasoconstriction.

PMID- 10883345
TI  - Intraneural growth of a capillary haemangioma of the cauda equina.
AB  - Solitary intraneural haemangiomas are very rare. A case of intraneural capillary
      haemangioma involving two nerve roots of the cauda equina is reported. The
      patient was a 63-year-old woman with a three years history of intermittent
      lumbalgia and numbness of the ventral surface of the left thigh. Magnetic
      resonance imaging detected an intradural extramedullary nodular space occupying
      mass at the level of the conus medullaris. Laminectomy of T12 and complete
      removal of the tumour were performed. Histopathological analysis demonstrated a
      capillary haemangioma. The tumour was located within the sheaths of a spinal
      nerve root. The lesion consisted of a myriad of small and very small vessels,
      reticularly arranged with normal nerve fascicles dispersed within the nodules of
      clustered capillaries. The present case of an intraneural capillary haemangioma
      of the cauda equina appears to be one of the first reported examples of this
      entity in the world's literature. The clinical presentation, diagnostic
      procedures and therapeutic options of intraneural haemangiomas of the conus
      medullaris and cauda equina are discussed. The current literature is reviewed.

PMID- 10883346
TI  - Oligodendrocytic gliomatosis cerebri.
AB  - We describe a very unusual case of gliomatosis cerebri (GC) with oligodendrocytic
      differentiation. A 65-year-old man presented with a convulsive seizure. Magnetic
      resonance (MR) documented diffuse enlargement of cerebral hemispheres, brainstem,
      and right cerebellar hemisphere. After admission, the patient manifested a
      progressive deterioration of his neurological condition. A right temporal
      craniotomy and temporal lobectomy were performed to obtain brain decompression
      and diagnosis. Pathological findings were those of a GC consisting of neoplastic
      oligodendrocytes. Oligodendrocytic GC is a very rare pathological condition.
      Diagnosis of GC is usually made at autopsy. Our case confirms that diagnosis by a
      combination of MR imaging and brain biopsy.

PMID- 10883347
TI  - Intraventricular malignant triton tumour.
AB  - The authors present the clinical and pathological features of a malignant triton
      tumour (MTT) in the lateral ventricle with neurofibromatosis type 1. A 57 year
      old man presented with disorientation and memory disturbance. A Computed
      tomographic scan and magnetic resonance imaging studies revealed an enhancing
      lesion in the left lateral ventricle. A parieto-occipital transcallosal approach
      was taken and resection of the lesion was performed. The operative findings
      suggested that the tumour arose from the perivascular nerves. The final
      pathological diagnosis was a MTT. This is the first case of an intraventricular
      MTT. Aggressive treatment including radical surgery combined with
      radiochemotherapy is recommended for a MTT of the central nervous system.

PMID- 10883348
TI  - Pure intracranial vagal neurinoma.

PMID- 10883349
TI  - Postoperative MR imaging in hemifacial spasm.

PMID- 10883350
TI  - [Research--publications--impact factor--"industry-method" corruption. Thoughts on
      a German phenomenon].

PMID- 10883351
TI  - [Neuropathic pain. The long path from mechanisms to mechanism-based treatment].
AB  - Clinical characteristics of neuropathic pain, i.e. pain after nervous system
      lesions, are burning spontaneous pain, shooting pain attacks and evoked pains.
      Partly interacting pathophysiological mechanisms at the peripheral and central
      nervous system may be responsible for initiation and maintenance of chronic
      neuropathic pain. (1) Peripheral nociceptive fibers can be abnormally sensitized.
      (2) Central nociceptive second order neurons in the spinal cord dorsal horn can
      also be sensitized, i.e. they are hyperexcitable and start responding to non
      noxious stimuli. (3) Degeneration of nociceptive neurons may trigger anatomical
      sprouting of low-threshold mechanosensitive terminals to central nociceptive
      neurons and may subsequently induce synaptic reorganization in the dorsal horn.
      By this mechanism activity in mechanosensitive neurons may be perceived as
      painful. (4) Peripheral nerve injury may induce a pathological interaction of the
      nociceptive system and the efferent sympathetic system. The different mechanisms
      can operate in concert in a single disease entity (e.g., postherpetic neuralgia)
      and also in one single patient. Distinct pathophysiological mechanisms lead to
      specific sensory symptoms (e.g., dynamic mechanical allodynia, cold
      hyperalgesia). Therefore, a thorough analysis of sensory symptoms may reveal the
      underlying mechanisms that are mainly active in a particular patient. In the next
      step novel drugs will be developed that address specifically the relevant
      mechanism combination. Drug therapies that are available today include NSAIDS,
      opioids, tricyclic antidepressants, anticonvulsives (carbamazepine, gabapentin),
      GABA-agonists, Capsaicin and NMDA-antagonists.

PMID- 10883352
TI  - Mivacurium or vecuronium for paediatric ENT surgery. Clinical experience and cost
      analysis.
AB  - BACKGROUND: The present study compared the quality of neuromuscular block and
      costs after equipotent doses of mivacurium and vecuronium in the context of
      paediatric ENT surgery. METHODS: A total of 30 children undergoing elective
      tonsillectomy were included and randomised in two groups (n = 15 for each)
      according to the neuromuscular blocking agent (NMBA) used. Anaesthesia was
      induced with alfentanil (15 micrograms/kg), propofol (3 mg/kg) and either 0.2
      mg/kg mivacurium or 0.14 mg/kg vecuronium. For maintenance of anaesthesia
      propofol (8-12 mg/kg/h) was given. Neuromuscular block was assessed by
      electromyography using train-of four stimulation and the following parameters
      were quantified: Twitch height (T1) 2 min after the initial bolus of the
      myorelaxant; duration until recovery to 10% T1, number and duration of bolus
      injections of the myorelaxant needed to maintain neuromuscular block to a T1 <
      10%. In addition, the intubating conditions, number of patients needing
      pharmacological reversal at the end of surgery, adverse reactions and the costs
      for neuromuscular block and pharmacological antagonization were assessed.
      RESULTS: Intubation conditions were comparable between both study groups:
      mivacurium--excellent: 7, good: 5, not acceptable: 1; vecuronium--excellent: 11,
      good: 4 (n.s.). T1 at 2 min was 16 (15)% for mivacurium and 6 (9)% for vecuronium
      (P < 0.05). Time to 10% T1 recovery was 6.1 (1.7) min for mivacurium and 21.8
      (3.7) min for vecuronium (P < 0.01). In the mivacurium group 7 repetitive doses
      (range: 4-18) were needed to maintain T1 < 10% during surgery, whereas children
      treated with vecuronium needed only 1 maintenance dose (range: 0-2) (P < 0.01).
      Two children in the mivacurium group and 11 in the vecuronium group required
      pharmacological reversal of the NMB at the end of surgery (P < 0.01). The overall
      costs of NMB were significantly higher in the mivacurium group as compared to
      vecuronium 12.88 (4.5) Euro vs 9.96 (2.4) Euro; P < 0.05. CONCLUSIONS: In
      conclusion, mivacurium-induced NMB is of very short duration in paediatric
      patients, and therefore repetitive doses are required to maintain a deep
      neuromuscular block. Nevertheless, residual paralysis is less frequent after
      mivacurium. The neuromuscular block after mivacurium was more expensive and
      residual paralysis less frequent compared to vecuronium.

PMID- 10883353
TI  - [Measurement of local oxygen parameters for detection of cerebral ischemia. The
      significance of cerebral near-infrared spectroscopy and transconjunctival oxygen
      partial pressure in carotid surgery].
AB  - The principle of, "selective shunting" during carotid endarterectomy requires a
      special concept to monitor neuronal function. The valence of the oxymetric
      methods, "near-infrared" spectroscopy (NIRS) and conjunctival oxygen tension
      (pcjO2) was determined with the reference method somatosensory evoked potentials
      (SEP). METHODS: In 41 patients undergoing reconstructive surgery on the internal
      carotid artery, recordings of the different methods were obtained under control,
      during carotid occlusion and during reperfusion. Cerebral ischemia was assumed if
      a complete loss of SEP appeared and an intraluminal shunt was placed.
      Conjunctival oxygen tension was measured continuously and simultaneously on the
      ipsi- and contralateral eye. RESULTS: In comparison to the reference method (SEP)
      the sensitivity and specificity of NIRS was 80% and 94%, respectively. The
      occlusion induced reduction of NIRS appeared 6.5 +/- 3.2 min earlier than the
      corresponding loss of SEP. Biocular determination of conjunctival oxygen tension
      was not able to detect hypoperfusion dependent ischemia during carotid occlusion.
      CONCLUSION: During carotid endarterectomy the measurement of conjunctival oxygen
      tension is not useful to detect cerebral ischemia. The use of NIRS as a single
      neuronal monitor is not appropriate to perform, "selective shunting". In contrast
      to SEP, however, NIRS is characterized by its rapid changes immediately following
      carotid occlusion. This non invasive method is likely to complete the standard
      method SEP in a modified monitoring concept of neuronal function during carotid
      endarterectomy.

PMID- 10883354
TI  - [Climatization of anesthetic gases using different breathing hose systems].
AB  - BACKGROUND: During general anaesthesia gas climate significantly is improved by
      performance of low flow techniques. Gas climatisation, however, markedly also
      will be influenced by the temperature loss at, and corresponding water
      condensation within the hoses, factors which are related to the technical design
      and material of the patient hose system. The objective of this prospective study
      was to investigate 1. how anaesthetic gas climatisation during minimal flow
      anaesthesia is influenced by the technical design of different breathing hose
      systems in clinical practice. 2. to investigate, whether a sufficient gas
      climatisation also can be gained with higher fresh gas flows if that hose system
      is used, proven beforehand to optimally warming and humidifying the anaesthetic
      gases. METHODS: Three different systems, a conventional two-limb hosing
      consisting of smooth silicone hoses, a coaxial hosing, and a hosing consisting of
      actively heated breathing hoses, attached to a Drager Cicero EM anaesthesia
      machine, were used during minimal flow anaesthesia with a fresh gas flow of 0.5
      l/min. Gas temperature and absolute humidity were measured at the tapered
      connection between the inspiratory limb and the breathing system as well as at
      its connection to the endotracheal tube. The best gas climatisation was observed
      if heated breathing hoses were used. Thus, using this hosing, additionally gas
      temperature and humidity in the inspiratory limb were taken at fresh gas flow
      rates of 1.0, 2.0 and 4.4 l/min respectively. Measurements were performed in all
      groups at all general anaesthesias lasting at least 45 minutes during the lists
      of eight different days each. RESULTS: In minimal flow anaesthesia, with all hose
      systems likewise, generally an absolute humidity between 17 to 30 mgH2O/l is
      reached at the endotracheal tube's connector during the course of the list. Only
      in the first cases of the day there was a short delay of 15 to 30 minutes before
      reaching a humidity of at least 17 mgH2O/l. Only with heated hoses, however,
      humidity frequently even exceeded 30 mgH2O/l. If conventional or coaxial hosings
      were used, during minimal flow anaesthesia gas temperatures in an acceptable
      range between 23 to 30 degrees C were measured at the tube connector. With heated
      hoses, however, warming of the gases was excellent with gas temperatures between
      28 to 32 degrees C. In minimal flow anaesthesia climatisation of the anaesthetic
      gases proved to be best if heated hoses were used. Thus, using heated hose
      systems another three trials with increasing fresh gas flow rates of 1.0, 2.0 and
      4.4 l/min respectively were performed. Whereas climatisation of the anaesthetic
      gases still was found to be optimal with a fresh gas flow of 1.0 l/min, the
      humidity dropped drastically to values lower than 17 mgH2O/l at 2.0 l/min and
      even down to 10 mgH2O/l at a flow rate of 4.4 l/min. Gas temperatures, however,
      turned out to be independent of the flow and remained at 28-32 degrees C, even at
      a flow as high as 4.4 l/min. CONCLUSIONS: Using conventional hose systems and
      coaxial hosings acceptable, but not optimal climatisation of the anaesthetic
      gases can be gained if minimal flow anaesthesia is performed. The use of a
      coaxial hose system seems to lead to improved climatisation in long lasting
      procedures only. In routine clinical practice, however, conventional and coaxial
      hose systems are similar in respect to the climatisation of breathing gases.
      Heated breathing hoses performed markedly better in terms of climatisation of the
      breathing gas than the coaxial and the conventional hose system. With this hosing
      not only sufficient but optimal moisture and temperature values are realized.
      Optimal climatisation, however, only can be gained if low flow anesthetic
      techniques with fresh gas flows equal or less than 1 l/min are performed. With
      higher fresh gas flow rates the humidity decreases markedly while high gas
      temperatures are maintained. (ABSTRACT TRUNCATED)

PMID- 10883356
TI  - [In Process Citation]

PMID- 10883355
TI  - [Neuroprotection in neuroanesthesia: current practices in Germany].
AB  - This survey collected and analyzed data on the current practice of clinical
      neuroprotection in neuroanesthesia in Germany. METHODS: The data were collected
      by a questionnaire sent to departments of anesthesiology in Germany in 1997 which
      provided care for neurosurgical patients on a routine basis, and which were
      registered members of the German Society of Anesthesiology and Intensive Care
      Medicine (DGAI). Since the questions concerning "neuroprotective therapy" were
      linked to a general survey on clinical neuroanesthesia performed by the
      scientific neuroanesthesia working group of the DGAI, the only departments that
      were assessed were those which had participated in an earlier study on
      neuroanesthesia in 1991. RESULTS: Of the completed questionnaires 63% could be
      included in the analysis. Approximately 75,000 cases were thus evaluated. Therapy
      varied considerably between departments. Following head trauma 69% of injured
      patients were managed with enhanced cerebral perfusion pressure (CPP) within the
      range of 70-90 mmHg. If necessary, CPP increase was induced by vasopressors
      (exogenous supply of catecholamines in 100% of instances) and the administration
      of fluids (97% of instances). The most commonly used therapeutic approaches to
      treat intracranial hypertension were mannitol (95% of instances),
      hyperventilation (91% of instances), cerebrospinal fluid drainage (89% of
      instances), and barbiturates (86% of instances). Tris (hydroxymethyl)
      aminomethane was administered in almost 49%, mild hypothermia in 37%, and
      hypertonic-hyperoncotic solutions in 28% of patients treated for an increase in
      intracranial pressure. Following intracranial aneurysm surgery "triple-H" therapy
      was used in 74% of patients, applied as hemodilution in 94% and as hypervolemia
      and hypertension in 87% of instances. Mild hypothermia was employed as a method
      of neuroprotection in 54% of the departments involved. It was used in 83% of
      patients during perioperative care and in 52% of patients during intensive care
      therapy. Specific neuroprotective drugs were applied in 68% of departments, with
      barbiturates (38% of instances), nimodipine (23% of instances), and
      corticosteroids (10% of instances) as the main agents named. These brain
      protective medications were administered especially in intracranial hypertension
      in 30%, in intracranial aneurysms in 21%, and in subarachnoid hemorrhages
      subsequent to head trauma in 18% of instances described. CONCLUSION: These
      findings demonstrate that the neuroprotective therapy administered in
      anesthesiological departments in Germany is not yet standardized, i.e., there is
      a wide variation. Although outcome was not assessed with this survey, it is
      conceivable that algorithms based on logical approaches in the sense of evidence
      based medicine could serve as tools to reduce morbidity and mortality.

PMID- 10883357
TI  - [In Process Citation]

PMID- 10883358
TI  - [The historical development of intensive care in Germany. Contemporary views. 15.
      Respiration, tracheotomy and prolonged intubation].

PMID- 10883359
TI  - [Significance of perfusion of the gastrointestinal tract in shock].
AB  - The splanchnic perfusion is reduced early in the course of any shock. The mucosa
      of the gut suffers most as it experiences a high oxygen demand even in the steady
      state. The specific arrangement of the micro vessels within the villus of the
      mucosa exposes the tip of the villus at the highest risk for ischemia,
      particularly in low flow states. As a consequence the integrity of the mucosal
      layer is compromised and dysfunction of the mucosal barrier may allow bacteria
      and toxins to translocate from the gut lumen. Activation of leukocytes and
      stimulation of cytokine synthesis may comprise a sustained inflammatory response
      syndrome. So far there is a good body of evidence that the splanchnic region may
      play an important role in the pathophysiological sequence from shock to organ
      dysfunction.

PMID- 10883360
TI  - [The effect of hepatosplanchnic circulation in treatment of trauma and sepsis.
      Beyond O2-supply O2-uptake relationship?].
AB  - Sepsis and SIRS are characterised by increased hepatosplanchnic blood flow and
      oxygen transport due to sepsis-associated hypermetabolism with enhanced oxygen
      uptake. Regional hypermetabolism may be linked with a mismatch of oxygen
      availability and demand potentially resulting in a pathological splanchnic oxygen
      uptake/supply dependency. Splanchnic hypermetabolism has been hypothesised to be
      due to increased hepatic gluconeogenesis caused by accelerated glucose precursor
      uptake resulting from increased release from the peripheral tissues. This
      increased precursor efflux is triggered by cytokines. The response of splanchnic
      haemodynamics and oxygen kinetics, however, to therapeutic interventions does not
      necessarily parallel the different metabolic pathways. Therefore, understanding
      of both tissue perfusion and oxygenation as well as metabolism is pivotal for
      evaluating the effects of different therapeutic strategies in intensive care
      medicine.

PMID- 10883361
TI  - [Protection of the mucosal barrier by nutritional strategies. What are the
      therapeutic options?].
AB  - The dysfunction of intestinal barrier allows the translocation of both endotoxin
      and whole bacterial organisms. It plays an important role in the development of
      multiple organ failure (MOF). The mucosa ia one component of this barrier.
      Trauma, atrophy and the "systemic inflammatory response syndrome" increase
      gastrointestinal permeability. These abnormalities may contribute to the
      pathophysiology of sepsis. Malnutrition per se compromises the gut's barrier
      function. Maintenance of gastrointestinal blood flow may be facilitated by
      (glutamine-enriched?) enteral diets. The most important conclusions of the
      majority of controlled trials support the concept of the very early enteral
      nutrition (within 24 hours after trauma): the outcome of seriously ill patients
      is improved, the rate of complications and infections is reduced.
      Gastrointestinal motility disorders may interfere with the initiation and
      tolerance of early enteral nutrition. They may be managed by prokinetic agents
      (cisapride, erythromycin) or by bypassing the stomach with a nasoenteric tube.

PMID- 10883362
TI  - [Immune function and organ failure. Immunomodulation with nutritional support--an
      update].
AB  - Today, substrates with immunomodulatory effects are not only identified in all
      groups of macronutrients, but also in the domains of vitamins and traceelements.
      Mainly they interfere with 3 areas of the immune response: 1. the mucosal barrier
      function, 2. the cellular defense function, and 3. the local or systemic
      inflammatory response. Enteral formulas enriched with immune-enhancing diets are
      already in clinical use to encounter "immunoparalysis" of cellular defense during
      critical illness. Considering defined outcome variables, indeed, current clinical
      studies point out some improvements. Using an evidence based approach, a grade A
      recommendation was proclaimed for its broad clinical use. For defined subgroups
      of patients, however, presenting with most severe appearances of SIRS and
      consecutive organ failure, the current concept of enteral immunonutrition remains
      to be a matter of debate, and the evidence of clinical benefits persist to be
      questionable.

PMID- 10883363
TI  - [Inflammation and immunoparalysis. What are the differential criteria?].
AB  - Multiple organ failure (MOF) may occur early or late after trauma. Besides direct
      physical injury of organs, compromise of the microcirculation by inflammation
      plays an important role in the pathogenesis of MOF. Inflammation also induces
      counterregulatory responses which may end up in immunoparalysis. As a result,
      infection and sepsis with additional inflammatory damage to the microcirculation
      ensue thereby contributing to the late development of MOF. In addition to this
      biphasic model of posttraumatic MOF, there is evidence that inflammation and
      immunoparalysis do not only occur in sequence to each other but in parallel early
      after surgical procedures. The aim of the present brief review is to summarize
      the posttraumatic mechanisms of inflammation and immunoparalysis and to discuss
      how to differentiate between both pathophysiologic states.

PMID- 10883364
TI  - [Undesirable intraoperative waking--a rare phenomenon?].

PMID- 10883365
TI  - [Accidental injections in PDA catheter].

PMID- 10883366
TI  - [Blood coagulation values for caudal anesthesia].

PMID- 10883367
TI  - [Acetylsalicylic acid].

PMID- 10883368
TI  - [Transport of intensive care patients].

PMID- 10883369
TI  - Paediatric brain tumours: an embryological perspective.
AB  - Primitive neuroectodermal tumours are amongst the most common paediatric tumours
      of the central nervous system. These tumours are composed of undifferentiated
      cells and a variable component of more differentiated cell types. Most analysis
      of these tumours has focused on molecules normally found in the differentiated
      cells or those found in all primitive neuronal precursors. In this article we
      describe recent advances in understanding of the molecular processes involved in
      normal neurogenesis. We discuss the relevance of these data to the biology of
      neuronal tumours and describe strategies we and others have adopted to
      investigate the usefulness of molecules found in undifferentiated neuronal
      tissues in understanding the events which underlie oncogenesis in this tumour
      type.

PMID- 10883370
TI  - Temporal lobe focal cortical dysplasia: MRI imaging using FLAIR shows lesions
      consistent with neoplasia.
AB  - Focal cortical dysplasia (FCD), a form of neuronal migration disorder, is a
      malformative lesion of the neocortex that occurs during development of the brain.
      It can cause partial and generalized epilepsy. Seizures occur at an early age and
      are often resistant to medication. Surgical resection has been found to be
      beneficial in these patients. Dual pathology, in the form of mesial temporal
      sclerosis, has been associated with FCD. At the Children's Hospital of Eastern
      Ontario, four patients with temporal lobe FCD have recently, been identified.
      This paper discusses how these children presented and how they were managed, with
      particular emphasis on their MRI findings and differential diagnoses. In three of
      the four patients neuroimaging studies showed lesions consistent with a
      neoplastic process because of the large volume and mass effect. Radiologically,
      FCD may mimic the MRI appearance of tumors, such as dysembryoplastic
      neuroepithelial tumors, primitive neuroectodermal tumors, gangliogliomas,
      oligodendrogliomas, and astrocytomas. These lesions are best visualized on fluid
      attenuated inversion recovery (FLAIR) imaging, a technique that has recently
      become applicable in the clinical setting, as we help demonstrate in this series.
      With better MRI capability, milder forms of FCD and microdysplasia may be
      distinguished.

PMID- 10883371
TI  - Pediatric intractable epilepsy: the role of presurgical evaluation and seizure
      outcome.
AB  - Surgical experience with long-term follow-up is limited in childhood intractable
      epilepsy, compared with adult epilepsy. To assess the role of each presurgical
      evaluation modality and to identify prognostic factors for favorable seizure
      control after epilepsy surgery, 38 children with intractable epilepsy who
      underwent surgery were retrospectively reviewed. Among the available preoperative
      evaluation modalities, PET and neuropsychological testing showed the highest
      rates of positive results, whereas MRI was the most concordant with EEG findings.
      During a follow-up period of at least 12 months, 26 of the 38 patients showed
      favorable seizure control (Engel classifications I and II). The best seizure
      control was achieved in patients with a temporal resection and discrete lesion on
      magnetic resonance imaging. In spite of the invasive study, the less satisfactory
      results followed an extratemporal resection. We conclude that epilepsy surgery
      benefits children with intractable epilepsy and that the role of invasive study
      should be reestablished according to the area of resection and presence of
      discrete lesion on MRI.

PMID- 10883372
TI  - Radiosurgery in the management of pediatric brain tumors.
AB  - A total of 114 patients with benign and malignant intracranial tumors were
      treated by Valentino at the Flaminia Radiosurgical Center using a Philips 6-MeV
      linear accelerator between 1987 and 1995. The tumor locations break down as
      follows: 36 in the cerebral hemispheres, 14 in the region of the
      hypothalamus/optic chiasm, 21 in the III ventricle/pineal region, 3 in the basal
      ganglia, 27 in the posterior fossa, 13 in the brain stem. Seventy-nine patients
      had multivariate/combined treatment consisting of surgery or biopsy followed by
      chemotherapy, radiotherapy and/or radiosurgery. Thirty-five were not operated on
      or biopsied but were treated primarily by radiosurgery, which was associated with
      chemotherapy and conventional radiotherapy. The short- and long-term results were
      evaluated separately for each pathology in an attempt to derive guidelines for
      future treatment. For tumors of the pineal region, we are of the opinion that
      radiosurgery is the treatment of choice in children and that more than one-third
      of patients can be cured by this means. The remaining patients require surgery
      and/or chemotherapy in addition. For medulloblastomas radiosurgery may be useful
      to control local recurrence if coupled with chemotherapy. In the case of
      ependymomas, partly because of the extreme malignancy of the lesions in our
      series, radiosurgery did not succeed in controlling local recurrence. We fear
      that limiting treatment to radiosurgery, rather than prescribing conventional
      radiotherapy when indicated, could permit CNS seeding. For craniopharyngiomas
      radiosurgery proved useful for controlling solid remnants. In glial tumors
      radiosurgery helped either to "sterilize" the tumor bed after removal or to treat
      remnants of the lesions in critical areas; for diffuse brain stem gliomas it
      should be considered the treatment of choice.

PMID- 10883373
TI  - Fractionated stereotactic radiotherapy for pediatric brain tumors: the Chicago
      children's experience.
AB  - Thirty-three children with a total of 35 benign/malignant brain and eye neoplasms
      were treated with fractionated stereotactic radiotherapy. In the first 11
      children immobilization for treatment was achieved with plaster of Paris casts or
      aquaplast masks. In the remaining 22 children the Laitinen stereoadapter was
      used. Radiation was delivered with noncoplanar static or rotational beams. The
      dose fractionation used was 50.4-60 Gy in 28-30 fractions in patients receiving
      treatment with curative intent, and 10-32 Gy at 2-4 Gy/fraction for
      reirradiation. The accuracy of daily treatment was < 2 mm. After a median follow
      up of 27 months, 22 of the 25 children treated with curative intent achieved
      local control. One child had progressive brain necrosis following 54 Gy in 30
      fractions for a pontine astrocytoma. The exact etiology of this complication is
      unknown. This series demonstrates that in children fractionated stereotactic
      radiotherapy using the Laitinen stereoadapter is well tolerated and accurate and
      results in good local control.

PMID- 10883374
TI  - Radiation-associated xanthomatous meningioma in a child.
AB  - Radiation-associated meningioma in a child is rare. We report a case of
      xanthomatous meningioma, a rare subtype even in the adult population, which
      occurred in a 10-year-old boy who had undergone irradiation therapy for
      ependymoma at the age of 2 years. Histological examination of the tumor revealed
      a mixture of meningothelial cells and abundant foamy xanthomatous cells, with no
      apparent atypical cellular features. Xanthomatous meningioma associated with
      therapeutic high-dose irradiation in a child has not yet been documented.
      Immunohistochemical studies and the clinical course are evaluated with a review
      of the literature.

PMID- 10883375
TI  - Chiasmatic low-grade glioma presenting with sacral intradural spinal metastasis.
AB  - Leptomeningeal metastasis of low-grade gliomas in children has been documented in
      several series, both at the time of diagnosis and at relapse. The authors report
      a unique case of chiasmatic low-grade astrocytoma presenting with signs and
      symptoms related to the metastatic site rather than the primary site. In this
      respect, the possibility of appearance of symptoms and signs related to
      leptomeningeal dissemination preceding the signs and symptoms belonging to the
      primary site should be considered in this type of benign tumours.

PMID- 10883376
TI  - Hemorrhagic subdural effusion complicating an endoscopic III ventriculostomy.
AB  - Subdural effusion, a common postoperative complication of extracranial shunting
      for hydrocephalus, is usually caused by excessive drainage of cerebrospinal
      fluid. Subdural effusion is thought to occur less frequently after a
      neuroendoscopic III ventriculostomy, and no reported cases have been symptomatic.
      We encountered a symptomatic subdural effusion with a component of hemorrhage 5
      days after the latter procedure was performed to treat massive hydrocephalus in a
      2-year-old boy.

PMID- 10883377
TI  - Short-term changes in movement frequency do not alter the spatial tuning of
      saccade-related neurons in intraparietal cortex.
AB  - Modulations of the firing rates of neurons in the lateral intraparietal area
      (LIP) have been observed during experiments designed to examine decision
      processing, movement planning, and visual attention. These modulations have been
      assumed to reflect a uniform scaling of spatially stationary response fields,
      which describe firing rate as a function of either visual target location or
      movement metrics. However, because complete response fields are rarely collected,
      the possibility exists that these modulations may reflect shifts in response
      field location or changes in response field size. Moreover, many of these
      observed changes in LIP neuronal activity are also correlated with experimental
      practices that alter the frequency with which particular visual stimuli are
      viewed and particular movements are produced. The effects of repeatedly
      presenting a particular target and eliciting a particular movement on the
      response fields of LIP neurons warrant closer inspection because manipulations of
      this type are known to alter both the location and size of the receptive fields
      of many cortical sensory neurons. To address this issue, we measured the response
      fields of neurons in intraparietal cortex under two conditions over a period of
      up to 2 h: one in which each of nearly 200 stimulus locations was equally likely
      to serve as the saccade target on a trial, and a second in which one stimulus
      location was up to 750 times likelier to serve as the saccade target on a trial
      than were any of the other stimulus locations. We found no shifts in response
      field location or changes in response field size when we altered the frequency
      with which particular movements were produced or particular visual stimuli were
      presented. These data suggest that the response fields of intraparietal neurons
      are stationary over short periods of time and under conditions similar to those
      typically used to study LIP neuronal activity.

PMID- 10883378
TI  - "Third tier" ventral extrastriate cortex in the New World monkey, Cebus apella.
AB  - The ventral extrastriate cortex adjacent to the second visual area was studied in
      the New World monkey Cebus apella, using anaesthetised preparations. The
      visuotopic organisation and myeloarchitecture of this region demonstrate the
      existence of a distinct strip of cortex, 3-4 mm wide, with an ordered
      representation of the contralateral upper visual quadrant, up to 60 degrees
      eccentricity. This upper-quadrant representation is probably homologous to the
      ventral subdivision of the third visual complex (V3v) of Old World monkeys, also
      known as the ventral posterior area. The representation of the horizontal
      meridian in V3v forms its posterior and medial border with V2, while the upper
      vertical meridian is represented anterior and laterally, forming a congruent
      border with the fourth visual area (V4). Central visual fields are represented in
      posterior and lateral portions of V3v, in the inferior occipital sulcus, while
      the periphery of the visual field is represented anteriorly, on the tentorial
      surface. Cortex anterior to V3v, at the ventral occipitotemporal transition, had
      neurones that had poor visual responses. No representation of the lower quadrant
      was found adjacent to V3v in ventral cortex. However, we observed cells with
      perifoveal receptive fields centred in the lower quadrant immediately dorsal to
      V3v, around the junction of the inferior occipital and lunate sulci. These
      observations argue against the idea that V3v is an area restricted to the ventral
      cortex in New World monkeys and support the conclusions of previous anatomical
      studies in Cebus that showed a continuity of myeloarchitecture and connectional
      patterns between ventral and lateral extrastriate cortices. Together, these data
      suggest that V3v may be part of a larger area that extends into dorsolateral
      extrastriate cortex, overlapping to some extent with the caudal subdivision of
      the dorsolateral area described in other New World monkeys.

PMID- 10883379
TI  - Modulation of exteroceptive suppression periods in human jaw-closing muscles
      induced by summation of nociceptive and non-nociceptive inputs.
AB  - Convergence of various afferent inputs onto brain-stem neurons may play an
      important role in the regulation of trigeminal motor function. The present study
      examined the efficacy of nociceptive and non-nociceptive perioral stimulation for
      the modulation of the two exteroceptive suppression periods (ES1 and ES2) in
      human jaw-closing muscles. The inhibitory jaw-reflexes, ES1 (10-15 ms onset) and
      ES2 (40-50 ms onset), were recorded as the surface electromyogram of masseter and
      temporalis muscles in 14 healthy subjects. Non-painful electrical stimuli were
      applied to the right mental nerve while the subject was biting at 50% of the
      maximal voluntary force. Five conditions were compared: baseline, repetitive
      tactile stimulation (1 Hz) on the right cheek, topical application of capsaicin
      (5%) on the right cheek, repetitive tactile stimulation plus capsaicin, and
      postbaseline. The perceived intensity of the electrical stimuli was evaluated by
      the subjects on a 0-10 rating scale. Capsaicin alone failed to induce significant
      changes of ES1 and ES2; tactile stimulation alone induced a significant delay in
      the onset of ES2 (P < 0.001). During repetitive tactile stimulation plus
      capsaicin, the duration of ES1 and ES2 was shortened (ES1 and ES2: P < 0.001) and
      the degree of suppression was reduced (ES1: P < 0.05; ES2: P < 0.005). Perceived
      intensity of the electrical stimuli was unchanged during the different
      experimental conditions. The present results suggest that summation of
      simultaneous nociceptive and non-nociceptive inputs plays an important role in
      the modulation of the neural pathways involved in the short-latency ES1 and long
      latency ES2.

PMID- 10883380
TI  - Functional plasticity in the interposito-thalamo-cortical pathway during
      conditioning. Role of the interstimulus interval.
AB  - In classic conditioning, the interstimulus interval (ISI) between the conditioned
      (CS) and unconditioned (US) stimulus is a critical parameter. The aim of the
      present experiment was to assess whether, during conditioning, modification of
      the CS-US interval could reliably produce changes in the functional properties of
      the interposito-thalamo-cortical pathways (INTCps). Five cats were prepared for
      chronic stimulation and recording from several brain regions along this pathway
      in awake animals. The CS was a weak electric shock applied on the interposed
      nucleus of the cerebellum in sites that initially elicited forelimb flexion
      (i.e., alpha motor responses) in three cats, and equal proportions of flexor and
      extensor responses in two cats. The US was an electric shock applied on the skin
      that elicited forelimb flexions. The motor and neurobiological effects of
      synchronous CS-US were compared with pairings in which the CS was applied 100 ms
      before US. Simultaneous and sequential application of CS and US produced
      different behavioral outcomes and resulted in different neural processes in the
      interposito-thalamo-cortical pathways (INTCps). The simultaneous presentation of
      stimuli only produced a small increase in excitability spreading to all the body
      representational zones of the primary motor cortex and a weak increase in the
      amplitude of the alpha motor response. In contrast, the sequential application
      led to a profound modification of the interposed output to neurons in the
      forelimb representation of the motor cortex. These robust neuronal correlates of
      conditioning were accompanied by a large facilitation of the alpha motor response
      (alpha-MR). There were also changes in the direction of misdirected alpha
      responses and an emergence of functionally appropriate, long-latency withdrawal
      forelimb flexion. These data revealed that, during conditioning, plastic changes
      within the thalamocortical connections are selectively induced by sequential
      information from central and peripheral afferents. This sequence significantly
      contributed to neural processes that are responsible for the acquisition,
      expression, and extinction of anticipatory flexion responses.

PMID- 10883381
TI  - Deficits in compensatory trajectory adjustments after unilateral sensorimotor
      stroke.
AB  - In a previous study, we demonstrated that the time-course for amplitude
      specification of goal-directed aiming movements is similar for individuals with
      and without a unilateral sensorimotor (SM) area lesion. However, subjects with a
      SM lesion performing with the arm ipsilateral to the side of the brain lesion
      were significantly less accurate than control subjects in an unpredictable
      condition. The unpredictable condition requires that subjects both formulate an
      initial plan for movement as well as adjust the response later as additional
      information about the target (i.e., the goal) is gained. It has been demonstrated
      that premovement planning and compensatory adjustments are the processes
      contributing largely to accuracy in targeted, isometric force responses. A
      statistical model has been described, which partitions response trajectories into
      the planned and compensatory adjustment components. The purpose of this study was
      to apply the statistical model to our previous data to determine if the
      difference in accuracy in those with unilateral stroke was due to a deficit in
      premovement planning, compensatory adjustments, or a combination of these two
      factors. We compared the performance of six subjects with unilateral stroke to
      that of matched control subjects participating in a timed-response movement
      paradigm. Subjects rapidly flexed or extended the forearm in order to capture a
      short (20 degrees) or long (45 degrees) target presented in either a fixed
      (predictable condition) or a random sequence (unpredictable condition). For
      individuals with stroke, the limb used was that ipsilateral to the side of the SM
      lesion. Time to prepare the response was manipulated by varying the time of
      target presentation relative to an auditory cue for movement initiation. Velocity
      was derived from the displacement data, and multiple regression was used to
      determine the effect of premovement planning and compensatory adjustments on end
      point accuracy. In the predictable condition, premovement planning contributed to
      final position more for the subjects with stroke [mean (SEM) = 0.50 (0.02)] than
      for the control subjects [0.36 (0.03)]. In the unpredictable condition, there
      were no differences between groups in percent variance due to planning [0.54
      (2.1) for the stroke group and 0.45 (2.8) for the control group]. This suggests
      that the ipsilateral (i.e., intact, undamaged) SM hemisphere significantly
      participates in the premovement planning of an aiming action. In contrast, for
      both predictable and unpredictable conditions, compensatory adjustments accounted
      for a smaller percentage of the variability in final position for the subjects
      with stroke than for the control subjects [0.09 (2.2) for the stroke group and
      0.25 (4.8) for the control group]. Therefore, the less accurate responses for the
      stroke group can be explained by deficits in the compensatory adjustment
      component. This suggests a substantial role for SM areas in the preparation and
      implementation of corrective actions while the effects of the pre-planned action
      are unfolding. In particular, we discuss the role of the ipsilateral SM areas in
      relation to parallel feedforward processing in unimanual aiming.

PMID- 10883382
TI  - Fetal porcine ventral mesencephalon graft. Determination of the optimal
      gestational age for implantation in parkinsonian patients.
AB  - Human fetal ventral mesencephalon tissue has been used as dopaminergic striatal
      implants in Parkinsonian patients, so far with variable effects. Fetuses from
      animals that breed in large litters, e.g., pigs, have been considered as
      alternative donors of dopaminergic tissue. The optimal gestational age of the
      porcine fetal donors has not been studied systematically. We collected ventral
      mesencephalic (VM) tissue from fetal pigs, embryonal ages E21, E28, E42, and E70,
      and examined the viability of the fetal VM cells after dissociation, the
      expression of tyrosine hydroxylase (TH) in culture, the presence of
      catecholamines, and the cellular survival and outgrowth up to 10 months after
      intrastriatal implantation in rats. The highest viability was found in
      suspensions prepared from E28 fetuses. The highest number of TH-positive cells
      was found in cell cultures prepared from E28 VM tissue. Explants with a
      gestational age of 28 and 42 days contained the largest amount of dopamine. Only
      E28-derived grafts showed TH-cell survival after implantation in rat striatum.
      Our results show that a gestational age of 28 days must be considered to be the
      optimal age for dopaminergic tissue derived from pig fetuses for therapeutic use
      as intrastriatal grafts in Parkinsonian patients.

PMID- 10883384
TI  - Getting the measure of vergence weight in nearness perception.
AB  - Combining multiple sources of information allows the human nervous system to
      construct an approximately Euclidean representation of near (personal) space.
      Within this space, binocular vergence is an important source of egocentric
      distance information. We investigated how the nervous system determines the
      significance (weight) accorded to vergence information when other (retinal)
      distance cues are present. We found that weight decreases with (1) increasing
      discrepancy between vergence information and other cues and (2) reduced vergence
      demand. The results also provided evidence that the nervous system represents
      vergence related distance information in units of nearness (the reciprocal of
      distance).

PMID- 10883383
TI  - Relative effects of the spatial and temporal characteristics of scanned surfaces
      on human perception of tactile roughness using passive touch.
AB  - The present experiments were designed to determine the ability of humans to
      estimate the roughness of raised dot surfaces using passive touch (subject
      immobile, surfaces scanned proximo-distally under the tip of the middle digit).
      In two initial experiments, the spatial period in the direction of the scan
      (longitudinal SP) was varied from 1.5 to 5 mm, while the transverse SP was kept
      constant at 2 mm. These surfaces were identical to those used in single unit
      recording experiments in primates which have shown that neurones in primary
      somatosensory cortex (SI) show graded changes in discharge over the same range of
      SPs. In the third and fourth experiments, roughness perception was studied over
      an extended range of longitudinal SPs (1.5-8.5 mm); transverse SP was either 1 or
      2 mm. We also examined the effects on roughness perception of presenting the
      surfaces at two different scanning speeds (approximately 50 and approximately 95
      mm/s), similar to those employed in the unit recordings. Magnitude estimates of
      perceived roughness increased in a nearly linear fashion as longitudinal SP was
      increased up to either 5 mm (experiments 1 and 2) or 8.5 mm (experiments 3 and
      4). A modest increase in the transverse SP elicited a small increase in roughness
      estimates, with preservation of the linear relation between roughness and
      longitudinal SP. The roughness sensation evoked by each surface was not affected
      by the change of the temporal pattern of scanning (Low and High speeds). These
      results showed that there is perceptual constancy for roughness across a twofold
      change in passive scanning speed, and that roughness is a function of the spatial
      characteristics of these raised dot surfaces. While a spatial code may underlie
      this observation, it is suggested that a simpler intensive code may be sufficient
      to explain the psychophysical observations. Based on the results of
      neurophysiological recordings in SI cortex, it is suggested that an invariant
      central representation of surface roughness could be extracted from the ambiguous
      peripheral signals that covary with roughness and the stimulating conditions
      (e.g. speed) by means of a simple subtraction process.

PMID- 10883385
TI  - Haptic detection thresholds of Gaussian profiles over the whole range of spatial
      scales.
AB  - In the literature only a small subset of the broad range of scales of human
      haptic perception has been explored. In this experiment, haptic detection
      thresholds have been investigated over a wide range of spatial scales. Computer
      controlled manufacturing techniques have made it possible to produce stimuli with
      sufficient accuracy to explore the gamut of haptic scales. We used stimuli with a
      convex or concave Gaussian-shaped profile running over the middle of a strip. The
      width of the Gaussian profile was varied between 150 microns and 240 mm. In this
      range of spatial scales a number of mechanisms, ranging from cutaneous
      mechanoreception to proprioception in fingers, arm and shoulder, contribute to
      haptic perception. The discrimination threshold between a flat surface and a
      Gaussian surface was investigated in a series of two alternative forced choice
      experiments on human subjects. The thresholds run from 1 micron for the narrowest
      Gaussian profiles to 8 mm for the broadest profile. The same thresholds were
      found for convex and concave shapes. Over the range of spatial scales, from 1 mm
      width on, the dependence of the detection threshold on the spatial width of the
      Gaussian profile was found to be a power function with an exponent of about 1.3.

PMID- 10883387
TI  - The excitability of human cortical inhibitory circuits responsible for the muscle
      silent period after transcranial brain stimulation.
AB  - The silent period after transcranial magnetic brain stimulation mainly reflects
      the activity of inhibitory circuits in the human motor cortex. To assess the
      excitability of the cortical inhibitory mechanisms responsible for the silent
      period after transcranial stimulation, we studied, in 15 healthy human subjects,
      the recovery cycle of the silent period evoked by transcranial and mixed nerve
      stimulation delivered with a paired stimulation technique. The recovery cycle is
      defined as the time course of the changes in the size or duration of a
      conditioned test response when pairs of stimuli (conditioning and test) are used
      at different conditioning-test intervals. The recovery cycle of the duration of
      the silent period in the first dorsal interosseous (FDI) muscle during maximum
      voluntary contraction after transcranial magnetic stimulation was studied by
      delivering paired magnetic shocks (a conditioning shock and a test shock) at 120%
      motor-threshold intensity. Conditioning-test intervals ranged from 20-550 ms. The
      recovery cycle of the silent period in the FDI muscle during maximum voluntary
      contraction after nerve stimulation was evaluated by paired, supramaximum bipolar
      electrical stimulation of the ulnar nerve at the wrist (conditioning-test
      intervals ranging from 20 to 550 ms). Electromyographic activity was recorded by
      a pair of surface-disk electrodes over the FDI muscle. The recovery cycle of the
      silent period after transcranial magnetic stimulation delivered through the large
      round coil showed two phases of facilitation (lengthening of the silent period),
      one at 20-40 ms and the other at 180-350 ms conditioning-test intervals, with an
      interposed phase of inhibition (shortening of the silent period) at 80-160 ms.
      The conditioning magnetic shock left the size of the test motor-evoked potentials
      statistically unchanged during maximum voluntary contraction. Paired transcranial
      stimulation with a figure-of-eight coil increased the duration of the test silent
      period only at short conditioning-test intervals. Conditioning nerve stimulation
      left the silent period produced by test nerve stimulation unchanged. In
      conclusion, after a single transcranial magnetic shock, inhibitory circuits in
      the human motor cortex undergo distinctive short-term changes in their
      excitability, probably involving different mechanisms.

PMID- 10883386
TI  - Role of neuronal nicotinic-acetylcholine receptors in the activation of neurons
      in trigeminal subnucleus caudalis by nicotine delivered to the oral mucosa.
AB  - To characterize the role of neuronal nicotinic acetylcholine receptors (nAChRs)
      in oral irritation and pain, we employed the method of c-fos immunohistochemistry
      to map the locations and numbers of brainstem neurons that express the immediate
      early gene, c-fos, after application of nicotine to the tongue, either alone or
      after pretreatment with cholinergic antagonists. Groups of anesthetized rats
      received the following chemicals delivered bilaterally to the dorsal tongue: (1)
      0.9% NaCl followed by nicotine (1%, 61 mM), (2) the nAChR antagonist,
      mecamylamine 0.1% (= 4.9 mM) followed by nicotine, (3) the muscarinic antagonist
      atropine (0.1% 1.46 mM) followed by nicotine, (4) atropine (1%, 14.6 mM) followed
      by nicotine, (5) 0.9% NaCl as a control, and (6) unstimulated controls. Two hours
      later, animals were perfused with phosphate-buffered saline followed by 4%
      paraformaldehyde through the aorta. Post-fixed brainstems were cut in 50-micron
      frozen sections and immunohistochemically processed for fos-like immunoreactivity
      (FLI). Following application of nicotine, there were significant increases in FLI
      compared with saline-treated controls in dorsomedial and ventrolateral aspects of
      the trigeminal caudalis. Pretreatment with either mecamylamine or the high (1%)
      concentration of atropine significantly reduced nicotine-evoked FLI in these
      areas, while pretreatment with the low (0.1%) atropine concentration did not
      significantly affect FLI. These results are consistent with the idea that
      nicotine activates nAChRs residing on lingual nociceptive fibers, which, in turn,
      excite neurons in trigeminal caudalis.

PMID- 10883388
TI  - The control of bimanual reach-to-grasp movements in hemiparkinsonian patients.
AB  - The basal ganglia are thought to participate in the control and programming of a
      variety of motor behaviours. However, the precise nature of this participation
      still remains to be clarified. This paper examines the proposal that the basal
      ganglia may serve to scale the amplitude of limb movements, with basal-ganglia
      dysfunction leading to the inappropriate scaling of intended motor activity.
      Several authors have suggested that examining the loss of function in Parkinson's
      disease (PD) patients offers perhaps the best way of learning about the role
      played by the basal ganglia in human motor function. While it has previously been
      reported that PD patients underscale the transport phase of their reach-to grasp
      movements, it has generally been assumed that the grasp component is normal. In
      this paper we demonstrate, using a group of hemiparkinson patients, that the
      scaling of the grasp component is also underscaled in PD patients.

PMID- 10883389
TI  - Brain regions involved in spatial frequency discrimination: evidence from fMRI.
AB  - The cortical areas underlying successive spatial-frequency discrimination were
      explored using functional magnetic resonance imaging (fMRI). In a steady-state,
      block-design paradigm, 12 subjects viewed a single fixation cross during a rest
      period, followed by an activation period consisting of the presentation of
      horizontal (distractors) and vertical (targets) sinewave gratings. Two tasks were
      performed: in the control task, subjects pressed a button after the second
      vertical grating was presented within each trial; in the discrimination task,
      subjects decided which target grating had the higher spatial frequency. Post
      processing consisted of off-line image registration to correct for head motion,
      spatial and temporal smoothing, and cross-correlation between each voxel time
      course and a phase-shifted stimulus time profile. The results indicate that
      striate, extrastriate, parietal, and prefrontal areas show significant BOLD
      (blood oxygen level dependent) effects during both discrimination and control
      tasks, with consistently higher activity levels in the discrimination task.

PMID- 10883390
TI  - Precision-grip force changes in the anatomical and prosthetic limb during
      predictable load increases.
AB  - This study examined precision-grip force applied to an instrumented test object
      held aloft while the weight of the object was predictably varied by transporting
      and placing loads (50, 100, or 200 g) atop the test object. Transport of the
      loads was performed either by the subject or the experimenter. Grip force was
      examined in four non-amputee control subjects and in the anatomical and
      prosthetic hand of a subject with a prosthetic device. As subjects transported
      the load, anticipatory grip-force changes occurred in the anatomical hands and
      prosthetic hand, which were scaled in relation to the load. When the experimenter
      transported the load to the anatomical hands of control subjects or the
      prosthetic user, anticipatory increases in grip force occurred that also were
      scaled in relation to load. However, when the experimenter transported the load
      to the prosthetic hand, anticipatory grip-force adjustments were absent. During
      the phase in which the load was being assumed by the postural hand, grip forces
      in the anatomical hands and prosthetic hand were further scaled to load demands.
      Ability to adapt grip force in the prosthetic hand during this phase suggested
      that the subject was utilizing sensory information from the residual limb to
      adjust grip force. Thus, while anticipatory changes precede the process of
      adaptation to load changes, actual sensory consequences resulting from added
      weight remain necessary to fully adapt grip force to load demands, even for the
      prosthetic user.

PMID- 10883391
TI  - Cortical potentials related to the nogo decision.
AB  - The go/nogo reaction time task has been frequently used to assess volitional
      inhibition. Psychophysiological studies of the correlates of the go/nogo decision
      have almost exclusively been concerned with N2 and P3 potentials of the event
      related potentials (ERPs). However, in studies where the EMG onset latency was
      available, it was obvious that this latency was shorter than or at least equal to
      the latencies of the studied cerebral potentials. In this study, by concurrent
      recording of the EEG and EMG activity we aimed to better define the temporal
      relationship between cortical activity and motor response. Particularly, we
      wanted to identify the early (i.e. pre EMG-onset) electrophysiological correlates
      of the nogo decision. We used a modified S1-S2 paradigm that involved a two-stage
      go/nogo decision. In this task both S1 and S2 were informative and required the
      subject to make a decision, but the nature of the decision differed. The decision
      at S1 involved whether to prepare a movement, whereas the decision at S2 involved
      whether to initiate or inhibit an already prepared response. To better visualise
      the nogo decision related components of the ERPs, the go ERPs were subtracted
      from the corresponding nogo ERPs and difference ERPs were formed. Before EMG
      onset, a small negative component common to both go/nogo difference traces and
      corresponding roughly with the N1 wave was detected. It is suggested that this
      early negativity may be a more specific electrophysiological reflection of the
      nogo decision proper.

PMID- 10883392
TI  - A method for preparing 2- to 50-micron-thick fresh-frozen sections of large
      samples and undecalcified hard tissues.
AB  - This article describes a method for preparing 2- to 50-micron-thick fresh-frozen
      sections from large samples and completely calcified tissue samples. In order to
      perform the more routine work involved, a tungsten carbide disposable blade was
      installed to a heavy-duty sledge cryomicrotome. An entire 10-day-old rat and bone
      and tooth samples from a 7-month-old rat were rapidly frozen. The frozen samples
      were attached to the cryomicrotome stage. The cutting surface of the samples was
      covered with a polyvinylidene chloride film coated with synthetic rubber cement
      and cut at -25 degrees C. The soft tissues and the hard tissues were
      satisfactorily preserved and all tissue cells were easily identifiable. Enzymatic
      activity in the fresh sections was much stronger than that in chemically fixed
      and/or decalcified sections. The sections permitted histological and
      histochemical studies without trouble. In addition, the sections can be used for
      multiple experiments such as immunohistochemistry, in situ hybridization, and
      electron microprobe X-ray micro-analysis. This method can be used with
      conventional cryomicrotome equipment.

PMID- 10883393
TI  - Detection of intracellular nitric oxide using a combination of aldehyde fixatives
      with 4,5-diaminofluorescein diacetate.
AB  - Using 4,5-diaminofluorescein diacetate (DAF-2DA), which was recently developed
      for the detection of intracellular nitric oxide (NO) in living cells, we examined
      the sensitivity of intracellular NO in cells treated with some fixatives.
      Cultured human umbilical vein endothelial cells loaded with DAF-2DA in the
      presence of 10(-6) M acetylcholine showed intense fluorescence when fixed in
      paraformaldehyde or glutaraldehyde, but no fluorescence could be detected after
      fixation in ethanol or acetone. Fluorescence generation depended on the
      combination of each aldehyde fixative with DAF-2, which is produced enzymatically
      from DAF-2DA within the cells. Subtracting the fluorescence intensity of non
      activated controls from that of cells activated by acetylcholine indicated the NO
      produced in the stimulated cells, since the control cells that took up DAF-2DA
      also generated fluorescence when treated with aldehyde fixatives. Thus, detection
      of intracellular NO by combining aldehyde fixatives with DAF-2DA is useful for
      examining the functions of NO in cells both in situ and in vivo.

PMID- 10883394
TI  - Disruption of epithelial tight junctions is prevented by cyclic nucleotide
      dependent protein kinase inhibitors.
AB  - Tight junctions (TJs), the most apical of the intercellular junctions, prevent
      the passage of ions and molecules through the paracellular pathway. Intracellular
      signalling molecules are likely to be involved in the regulation of TJ integrity.
      In order to specifically investigate the role of protein kinase A (PKA) in the
      maintenance of epithelial TJ integrity, calcium-switch experiments were
      performed, in which calcium was removed from EpH4 and MDCK culture medium, in the
      absence or presence of the PKA inhibitors H-89 or HA-1004. Removal of calcium
      from the culture media of the epithelial cells resulted in disruption of the TJs,
      characterised by a loss of membrane association of the TJ-associated proteins
      occludin, ZO-1 and ZO-2, by a loss of TJ strands, by a marked decrease in the
      transepithelial electrical resistance and by a dramatic increase in the
      transepithelial permeability to tracers. The association of occludin, ZO-1 and ZO
      2 with the actin cytoskeleton is not affected. In contrast, when the removal of
      calcium was performed in the presence of either the PKA inhibitor H-89 or HA
      1004, all barrier characteristics were preserved. Our data indicate that
      following the removal of calcium from the culture medium of epithelial cells in
      vitro, PKA is activated and subsequently is involved in the disruption of TJs.

PMID- 10883395
TI  - Enzyme-histochemically detectable glucose-6-phosphatase is present in chorion
      laeve trophoblasts of human fetal membranes.
AB  - The purpose of the present study was to demonstrate the presence of glucose-6
      phosphatase (G6Pase) in fetal membranes from various gestational ages (20-40
      weeks of gestation). Ultrastructural enzyme-histochemical analysis of G6Pase was
      performed using cerium and lead as capturing agents. Precipitates indicating
      G6Pase activity were present mainly in the endoplasmic reticulum and partly in
      the nuclear envelope of chorion laeve trophoblasts, but absent in amniotic
      epithelial cells. Stringent histochemical control experiments performed ensured
      specific detection of G6Pase activity. The results indicate that histochemically
      detectable G6Pase is present in the chorion laeve trophoblasts of human fetal
      membranes. This enzyme may have some physiological significance in carbohydrate
      metabolism in human fetal membranes and regulation of amniotic fluid glucose
      concentration.

PMID- 10883396
TI  - Nuclear matrix provides linkage sites for translocated NF-kappa B: morphological
      evidence.
AB  - In response to the binding of extracellular ligands to cell surface receptors,
      multiple transcription factors are activated in the cytoplasm and translocated
      into the nucleus where they exert positive or negative control over cellular
      genes. The human transcription factor NF-kappa B family regulates the expression
      of a large number of genes involved in the host defence mechanism. They are
      typically present in the cytoplasm bound to the inhibitory I kappa B proteins.
      The activation of NF-kappa B involves the signal-induced degradation of these
      proteins, allowing NF-kappa B to translocate to the nucleus. In this study, by
      multiparametric analysis, we recognise in RPMI-8402 DMSO-activated cells the
      intracellular movement of transcription factor NF-kappa B providing its definite
      intranuclear collocation. Intact cells, purified nuclei and nuclear matrix
      preparations after 4 h of treatment were processed for morphological and
      biochemical analyses. Light and electron microscope observations show, in
      untreated cells, the presence of NF-kappa B protein homogeneously retained in the
      cytoplasm. Treated cells display a massive presence of NF-kappa B at the nuclear
      level bound to the interchromatin region. Immunoblotting of the same specimens
      confirms the strong association of NF-kappa B with the nuclear scaffold. Taken
      together, the data presented in this manuscript support a model where DMSO
      treatment provokes the cleavage and translocation of NF-kappa B from the
      cytoplasm to the nucleus and, in particular, in the proteinaceous network of the
      nuclear matrix sustaining the active role of this subcellular structure on
      regulation of eukaryotic gene expression.

PMID- 10883397
TI  - Expression of the cholinergic gene locus in pulmonary arterial endothelial cells.
AB  - In the pulmonary vasculature of man, pig and guinea-pig, acetylcholine (ACh)
      exerts a relaxant effect by interacting with muscarinic receptors located on
      endothelial cells. The present experiments were designed to detect the endogenous
      source of ACh in the pulmonary vasculature. For this purpose, we investigated
      whether pulmonary artery endothelial cells contain elements of the "cholinergic
      gene locus", the ACh synthesising enzyme choline acetyltransferase (ChAT) and the
      vesicular ACh transporter (VAChT). ChAT mRNA was detected by means of reverse
      transcription polymerase chain reaction (RT-PCR) in endothelial cells of porcine
      pulmonary arteries freshly isolated and after 7 days in culture. ChAT protein was
      demonstrated in endothelial cells in vitro and in situ. ChAT immunoreactivity was
      present in endothelial cells freshly isolated and after 2, 4, 7, and 9 days in
      culture. Tissue sections from extra- and intraparenchymal pulmonary arteries of
      man, pig and guinea-pig expressed a mosaic pattern of ChAT-positive and -negative
      endothelial cells. VAChT mRNA was detected by RT-PCR in rat pulmonary artery and
      in endothelial cells isolated from human and porcine pulmonary trunk. The
      detection of VAChT and ChAT mRNA and the demonstration of ChAT protein in vitro
      and in situ suggest that the endothelium is an endogenous source of ACh in the
      pulmonary vasculature.

PMID- 10883398
TI  - The apical membrane of intestinal brush cells possesses a specialised, but
      species-specific, composition of glycoconjugates--on-section and in vivo lectin
      labelling in rats, guinea-pigs and mice.
AB  - Brush cells are specialised epithelial cells that are assumed to represent
      chemoreceptors of the digestive tract. They comprise a small population of the
      epithelial cells lining the intestine, possess a unique ultrastructure and, in
      many aspects, resemble the receptor cells of taste buds. To characterise
      glycoconjugates possibly involved in a sensory function, we investigated brush
      cells in the small intestine of three species using lectin histochemistry in
      confocal light and thin-section electron microscopy. Brush cells of rats were
      selectively labelled by the sialic acid-specific lectin Maackia amurensis
      agglutinin, those of guinea-pigs by the D-galactose-specific lectin Bandeiraea
      simplicifolia agglutinin, isolectin B4 and those of mice by the L-fucose-specific
      lectin Ulex europaeus agglutinin lectin I. Lectin binding sites were consistently
      located in the glycocalyx of the apical membrane and in that of cytoplasmic
      vesicles. In vivo lectin labelling revealed that the glycoconjugates of the
      apical membrane are accessible under physiological conditions, that brush cells
      do not endocytose and that they probably possess a high membrane turnover rate.
      The results show that specialisations exist in the composition of glycoconjugates
      forming the glycocalyx of brush cells in all species investigated. The presence
      of brush cell-specific glycoconjugates would be in accordance with the current
      hypothesis of a receptive function of brush cells. Differences in the specific
      glycosylation patterns among rats, guinea-pigs and mice indicate that species
      specific adaptations exist.

PMID- 10883399
TI  - Ultrastructural study of relationships between c-kit immunoreactive interstitial
      cells and other cellular elements in the human colon.
AB  - C-kit immunocytochemistry was performed on ultrathin sections of human distal
      colon. Our attention was focused on relationships between c-kit immunoreactive
      interstitial cells (c-kit ICs) and muscular cells and nervous elements located in
      the external muscular layers of the colonic wall. C-kit ICs established membrane
      apposition with both nerve fibers and smooth muscle cells of, respectively, the
      longitudinal and circular muscle layers, the myenteric area, and the extremus
      submucosus plexus. C-kit ICs also surrounded the external submucosus plexus and
      established membrane appositions with nerve elements located inside the myenteric
      ganglia. These membrane appositions were observed either at the level of the c
      kit IC bodies or at that of their cytoplasmic processes. In some cases, membrane
      appositions were observed concomitantly between the c-kit ICs, nerve fibers, and
      smooth muscle cells. In all the regions studied, the c-kit ICs were also found to
      be located in the close vicinity of blood vessels and to have established close
      contacts with non-immunoreactive fibroblast-like cells. The results of the
      present study shed essential light on the relationships of c-kit ICs with the
      neighboring muscle cells and nerve elements, and confirm that the intercalated c
      kit ICs well fit with the so-called "interstitial cells of Cajal".

PMID- 10883400
TI  - Improved extraction procedure for carotenoids from human milk.
AB  - An improved method for the extraction of the major carotenoids from human milk is
      described. Carotenoids were extracted from milk first with ethanol and n-hexane.
      Then, polar xanthophylls were extracted from n-hexane into ethanol/water. The
      remaining n-hexane was evaporated, the residue combined with the ethanolic milk
      fraction and the mixture briefly saponified. Carotenoids were extracted from the
      hydrolysate with n-hexane, combined with the polar xanthophylls from the non
      saponified ethanol/water-extract and separated by HPLC. Using this method we were
      able to significantly improve the recovery of xanthophylls such as lutein and
      zeaxanthin from human milk. The recovery rate of all carotenoids was > 90%. This
      method might not only be of value for milk but should be especially useful in the
      extraction of carotenoids from human tissues such as the adipose tissue.

PMID- 10883401
TI  - Vitamin A in blood plasma and urine of dogs is affected by the dietary level of
      vitamin A.
AB  - Dogs differ from other species with respect to the occurrence of a high
      percentage of retinyl esters in blood plasma and the excretion of substantial
      amounts of vitamin A in the urine. Our investigation focussed on the effects of
      different concentrations of vitamin A in the diet, ranging from concentrations
      below NRC requirements of 25 IU/kg body weight (BW) to 2400 IU/kg BW, on the
      levels of retinol and retinyl esters (palmitate/oleate and stearate) in canine
      blood plasma and urine. The plasma levels of retinyl esters paralleled the levels
      of vitamin A in the feed (r = 0.91; p < 0.001). The highest plasma level (12.1 +/
      0.4 mg/l) was observed at the highest level in the diet. This observation may be
      explained by the fact that in dogs retinyl esters are associated with
      lipoproteins. Even under prolonged feeding on vitamin A levels below NRC
      requirements, retinyl esters were still present in the plasma (2.8 +/- 0.1 mg/l).
      Levels of retinol were not affected (1.2 +/- 0.03 vs. 1.0 +/- 0.03 mg/l,
      respectively). In the urine, the concentration of retinol and retinyl
      palmitate/oleate increased with the first increase of vitamin A in the diet to
      1.2 +/- 0.4 mg/l of total vitamin A. Urinary levels were elevated and fluctuated
      with up to four peaks while dietary vitamin A levels were above NRC requirements.
      But the amount of retinol and retinyl esters excreted did not show any dependence
      on the amount of vitamin A in the diet. When the amount of vitamin A in the diet
      was at or below requirements, only traces of retinol and retinyl esters were
      detected in urine. Thus, contrary to current knowledge for most other mammals,
      retinyl ester levels in plasma and retinol and retinyl esters in the urine of
      dogs proved to be clearly but differently affected by the amount of vitamin A
      supplied with the diet. Contrary to retinol, plasma levels of retinyl esters
      closely reflect the actual supply of vitamin A with the feed. The occurrence of
      retinol and retinyl esters in urine may, however, be due to dietary supply of
      vitamin A in excess of standard requirements, thereby providing a useful
      indicator of a dietary supply of vitamin A above requirement. The mechanism
      involved in the possible regulation of urinary excretion of retinol and retinyl
      esters remains to be elucidated.

PMID- 10883402
TI  - Effects of retinoic acid and 1,25-dihydroxyvitamin D3 on IFN-gamma secretion by
      mononuclear leukocytes from nulliparous and postparturient dairy cattle.
AB  - Individual and combined effects of several isomers of retinoic acid (RA) and 1,25
      dihydroxyvitamin D3 (1,25-(OH)2D3) on interferon-gamma (IFN-gamma) secretion by
      blood mononuclear leukocytes (MNL) from nulliparous and postparturient Holstein
      cattle were evaluated in vitro. In the first experiment, effects on incubation
      period (24 to 72 hours) and time of supplementation (0 to 32 hours) with all
      trans, 9-cis, 13-cis-, and 9,13-dicis-RAs (0 to 100 nM) on IFN-gamma secretion by
      pokeweed mitogen (PWM)-stimulated (0 and 10 micrograms/ml) MNL from nulliparous
      cattle were evaluated. In the second experiment, MNL from postparturient cows
      (bled at 0, 2, 4, and 16 days postpartum) were stimulated with PWM (0 and 10
      micrograms/ml) in the presence of RA isomers (9-cis- or 9,13-dicis-RA; 0 to 100
      nM), 1,25-(OH)2D3 (0 to 100 nM), or with combinations of these metabolites. The
      results show that individual isomers of RA had no effect on IFN-gamma secretion
      by PWM-stimulated MNL from nulliparous or postparturient cows. Furthermore 1,25
      dihydroxyvitamin D3 inhibited IFN-gamma secretion by MNL from nulliparous and
      postparturient dairy cows; however, the degree of inhibition was greater when 9
      cis- and 9,13-dicis-RA were also present in the cultures. Finally mononuclear
      leukocytes from postparturient dairy cows produced substantially less IFN-gamma
      than did MNL from nulliparous cattle. It is concluded that retinoic acids
      individually did not affect the capacity of leukocytes from dairy cattle to
      secrete IFN-gamma. This result is in marked contrast to studies in monogastric
      species indicating that RAs inhibit IFN-gamma secretion by peripheral blood T
      cells. Inhibition of IFN-gamma secretion by 1,25-(OH)2D3 was potentiated by 9-cis
      and 9,13-di-cis-retinoics acids, suggesting that an excess of dietary vitamins A
      and D may compromise further the naturally immunosuppressed postparturient dairy
      cow. Additional research is necessary to determine if the combined effects of
      these metabolites on IFN-gamma secretion represent an increased susceptibility of
      the dairy cow to infectious diseases during the periparturient period. Lower
      secretion of IFN-gamma by MNL from postpartutient dairy cows, relative to
      nulliparous cattle, suggests that recently-calved cows are naturally
      immunosuppressed.

PMID- 10883403
TI  - Characteristics of male vitamin supplement users aged 50-59 years in France and
      Northern Ireland: the PRIME Study. Prospective Epidemiological Study of
      Myocardial Infarction.
AB  - The prevalence and characteristics of vitamin supplement users were assessed in
      7538 male subjects aged 50-59 from France and 2468 from Northern Ireland. In
      France, 15% of subjects used vitamin supplements; users were significantly
      younger, had a lower body mass index, a higher educational level, had more
      frequently a hard physical job, reported more frequently a personal history of
      disease and were less frequently retired or inactive than non-users. In Northern
      Ireland, 21% of subjects were vitamin supplement users; users had a lower body
      mass index, drank less alcohol, had a higher educational level, were more
      frequently non-smokers and professionally active, and reported a hard physical
      job and the practice of leisure sports more frequently than non-users. Finally,
      vitamin supplement users in Northern Ireland had a lower consumption of alcohol,
      smoked less, had a lower frequency of personal history of disease and were more
      frequently on dietary therapy for hypertension or dyslipidaemia than their French
      counterparts. We conclude that vitamin supplement use is associated with a
      healthier lifestyle and with dietary measures against hypertension and
      dyslipidaemia in Northern Ireland. The less favorable lifestyle observed for
      vitamin supplement users in France awaits further investigation.

PMID- 10883404
TI  - Reduction in carbonic anhydrase activity in the tongue epithelium and
      submandibular gland in zinc-deficient rats.
AB  - We investigated the effects of zinc deficiency on carbonic anhydrase (CA)
      activity in the tongue epithelium and submandibular gland in rats. Male 4-week
      old SD rats were given free access to a diet containing 2.2 (zinc-deficient), 4.1
      (low-zinc), or 33.7 (zinc-sufficient) mg zinc/kg diet for 6 weeks. Rats in the
      fourth group (receiving 33.7 mg zinc/kg) were pair-fed against the zinc-deficient
      rats. Biochemical analysis at the end of the experimental period indicated that
      zinc deficiency significantly reduced CA activity in the tongue epithelium and
      submandibular gland, and the CA activity levels in these tissues seemed to
      parallel the dietary zinc levels. By enzyme histochemistry, an intensely positive
      reaction for CA was observed in the middle and basal regions of the taste buds in
      the circumvallate papilla in the zinc-sufficient and pair-fed (control) rats. The
      cells in von Ebner's glands also showed a strong positive reaction in control
      rats, although only a weak reaction product was found in zinc-deficient rats.
      These results suggest that CA activity is affected by the dietary content of
      zinc, which is considered to be an indispensable factor for the maintenance of
      normal taste sensation.

PMID- 10883405
TI  - Risk of iron overload among middle-aged women.
AB  - Iron overload, expressed as increased body iron stores, has been recognized as a
      potential hazard because it promotes the generation of oxygen radicals. We
      analyzed factors associated with serum ferritin levels (an indicator of body iron
      stores) among middle-aged women with a high prevalence of nutrient supplement
      use. Serum ferritin concentrations were determined on automated immunoassay for
      487 healthy women with the mean age of 57 years who participated in the New York
      University Women's Health Study. The mean serum ferritin concentration in
      postmenopausal women was more than twice that in premenopausal women. Serum
      ferritin concentrations progressively increased with advancing age, but
      adjustment for menopausal status considerably weakened this association. Among
      non-dietary factors, nonwhite ethnicity, obesity and cigarette smoking were
      positively associated with serum ferritin concentrations. After adjustment for
      these factors and for menopausal status, serum ferritin levels were positively
      associated with meat intake and multivitamin use and inversely associated with
      breakfast cereal consumption. However, none of these lifestyle factors positively
      associated with serum ferritin levels had a significant impact on serum ferritin
      levels above 100 ng/ml (approximately equal to median concentration). Our results
      suggest that iron overload seems unlikely among middle aged women through their
      diet and nutritional supplements.

PMID- 10883406
TI  - Vitamin and nutritional status in Cuban smokers and nonsmokers in the context of
      an emerging epidemic neuropathy.
AB  - A prospective survey was conducted in a random sample of smokers (SMO) and non
      smokers (NON) men living in Havana. The aim of the survey was to investigate
      metabolic and dietary parameters discriminating between SMO and NON volunteers,
      which could explain underlying mechanisms to the higher risk of Epidemic
      Neuropathy (51,000 reported cases in Cuba from late 1991) previously demonstrated
      in the Cuban smoker. Forty three blood markers were determined and dietary
      intakes evaluated during 4 seasonal periods. alpha-carotene, beta-carotene, beta
      cryptoxanthin, total carotenoids and riboflavin blood concentrations were lower
      in SMO vs. NON subjects. Activities of glutathione reductase and
      butryrylcholinesterase were lower in the SMO group, as did total protein levels.
      Copper and thiocyanates were higher in SMO subjects. Most of the dietary
      parameters did not differ between the two groups of volunteers. Low biologically
      available quantities of carotenoids and riboflavin from low dietary intakes and
      depletion through smoking would be the main precipitating factors of Epidemic
      Neuropathy. Protein depletion and copper delivery via tobacco smoke, sunlight
      exposure, level of physical activity and high consumption of cigarettes, in a
      context of low dietary supplies concerning especially B vitamins, were probably
      aggravating factors through oxidative stress and impairment of cyanide
      detoxification.

PMID- 10883407
TI  - Food and nutrient intakes in a group of 11 to 16 year old Swiss teenagers.
AB  - Better knowledge of the dietary intake of teenagers is necessary to help health
      professionals to provide better advice on an individual and data for prevention
      and health programme. We carried out a dietary survey by 3-day records technique
      in a group of adolescents living in the Canton of Vaud, Switzerland. Food habits
      were traditional but rich in refined products and poor in plant food. Mean daily
      energy intake, which was 8025 kJ for the girls and 9350 kJ for boys, was lower
      than the recommended dietary allowances, especially for girls. Independently of
      the gender, breakfast represented 19% of the total daily energy intake, lunch 31%
      and dinner 29%. Total energy provided by snacks was 23.0% for girls and 20.4% for
      boys. The percentage of energy supplied by the afternoon snack was 15.8% for the
      girls and 13.3% for the boys. The source of energy was 14% from protein, 37% from
      fat and 49% from carbohydrates. A high percentage of adolescents had low
      micronutrient intakes (vitamins A, E, B1, B6, C, folates and for minerals
      magnesium, calcium and iron). An increase intake of vegetables and fruit should
      thus be strongly encouraged; snacking could offer a target vector to improve
      dietary nutritional quality.

PMID- 10883408
TI  - Lipid metabolism in equines fed a fat-rich diet.
AB  - The hypothesis tested was that dietary fat, when compared with an isoenergetic
      amount of non-structural carbohydrates, stimulates lipolysis in adipose tissue
      and also stimulates the fatty-acid oxidative capacity in skeletal muscle from
      horses. Six adult horses were fed a high-fat, glucose or starch containing diet
      according to a 3 x 3 Latin square design with feeding periods of three weeks. The
      diets were formulated so that the intake of soybean oil versus either glucose or
      corn starch were the only variables. In accordance with previous work, whole
      plasma triacylglycerol (TAG) concentration decreased significantly by 58%
      following fat supplementation. This fat effect was accompanied by a 247% increase
      in lipoprotein lipase (LPL) activity in post-heparin plasma. The dietary
      variables did neither significantly affect the basal in vitro lipolytic rate nor
      the lipolytic rate after adding noradrenaline. There was no significant diet
      effect on the activities of hexokinase and phosphofructokinase as indicators of
      glycolytic flux and citrate synthase and 3-hydroxy-acyl-CoA dehydrogenase as
      indicators of fatty-acid oxidative capacity. The concentrations of muscle
      glycogen and TAG were not affected by fat supplementation. It is concluded that
      our hypothesis is not supported by the present results.

PMID- 10883409
TI  - Current and emerging second-generation triptans in acute migraine therapy: a
      comparative review.
AB  - Sterile neurogenic inflammation within cephalic tissue, involving vasodilation
      and plasma protein extravasation, has been proposed as a pathophysiological
      mechanism in acute migraine. The action of 5-hydroxytryptamine (5-HT1B/1D)
      agonists--so-called triptans--on receptors located in meningeal arteries (5-HT1B)
      and trigeminovascular fiber endings (5-HT1D) has an inhibitory effect on this
      neurogenic inflammation. Recently, a series of second-generation 5-HT1B/1D
      agonists (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, and
      zolmitriptan) have been developed and are reviewed in this article. Their in
      vitro pharmacological properties, pharmacokinetics, clinical efficacy, drug
      interactions, and adverse effects are evaluated and compared to the golden
      standard in the treatment of acute migraine, sumatriptan.

PMID- 10883410
TI  - Commentary on the FDA draft guidance for bioequivalence studies for nasal
      aerosols and nasal sprays for local action: an industry view.
AB  - In June 1999, the Food and Drug Administration issued draft guidance for
      bioequivalence studies for nasal aerosols and nasal sprays for local action. The
      purpose of this opinion paper is to highlight the need for a balanced scientific
      debate before this guidance is used by underscoring the areas in the document
      that are in opposition to prevailing scientific understanding.

PMID- 10883411
TI  - Use of tangential visual symbols to increase the long-term learning process:
      applications of linkage in teaching pharmacological principles of addiction.
AB  - Medieval and Renaissance teaching techniques using linkage between course content
      and tangentially related visual symbols were applied to the teaching of the
      pharmacological principles of addiction. Forty medical students randomly divided
      into two blinded groups viewed a lecture. One lecture was supplemented by
      symbolic slides, and the second was not. Students who viewed symbolic slides had
      significantly higher scores in a written 15-question multiple-choice test 30 days
      after the lecture. These results were consistent with learning and semiotic
      models. These models hypothesize a linkage between conceptual content and
      perception of visual symbols that thereby increases conceptual retention. Recent
      neurochemical research supports the existence of a linkage between two chemically
      distinct memory systems. Simultaneous stimulation of both chemical systems by
      teaching formats similar to those employed in the study can augment neurochemical
      signaling in the neocortex.

PMID- 10883412
TI  - Antihypertensive effect of low-dose hydrochlorothiazide alone or in combination
      with quinapril in black patients with mild to moderate hypertension.
AB  - In this study, using 24-hour ambulatory blood pressure (BP) monitoring, the
      authors assessed the potential for BP control using hydrochlorothiazide (HCTZ,
      12.5 mg daily), given as a monotherapy over 12 months to 49 black South African
      patients with mild to moderate hypertension (mean day diastolic blood pressure
      [DBP] > or = 90 and < 115 mmHg). Uncontrolled patients received fixed combination
      of quinapril/HCTZ 10/12.5, 20/12.5, and 20/25 mg, with dose titration at 3
      monthly intervals if BP control was not achieved (day DBP < 90 mmHg). Overall,
      profound and sustained BP reduction was observed at the end of the study. The 24
      hour BP decreased from 151 +/- 14/98 +/- 7 to 136 +/- 15/87 +/- 9 mmHg (p <
      0.0001 at end of study vs. baseline); the mean day BP decreased from 155 +/-
      14/104 +/- 7 to 140 +/- 15/91 +/- 10 mmHg (p < 0.0001 at end of study vs.
      baseline). The overall control (mean day DBP < 90 mmHg) and response (decrease in
      day DBP > or = 10 mmHg) rates were 49% and 61%, respectively. At the end of the
      study, only 2 patients (4%) remained on treatment with HCTZ. Out of the initial
      12 patients controlled on HCTZ at 3 months (12/49, 24%), 5 patients remained
      controlled at 6 months and only 1 patient at 12 months. In contrast,
      quinapril/HCTZ combinations maintained their antihypertensive effect up to 9
      months, with a significant number of patients (22/49, 45%) requiring the highest
      dose of the combination (20/25 mg daily). In conclusion, low-dose HCTZ should not
      be recommended as monotherapy in black patients with mild to moderate
      hypertension due to the fact that the BP-lowering effect is attenuated already at
      6 months of treatment, with most patients requiring the addition of the ACE
      inhibitor.

PMID- 10883413
TI  - Product equivalence study comparing the tolerability, pharmacokinetics, and
      pharmacodynamics of various human immunoglobulin-G formulations.
AB  - In this randomized, double-blind, parallel-group study, a commercially available
      human immunoglobulin-G product, IVIG, was compared with two test formulations:
      (1) IVIG-N, which is a nanofiltered formulation of IVIG, and (2) IVIG-L, which is
      a nanofiltered, liquid, ready-for-use IgG formulation containing nicotinamide, L
      proline, and L-isoleucine as stabilizers. Three groups of 10 healthy subjects
      each received a single 0.6 g/kg dose of one of the formulations infused over 3.5
      to 6.8 hours, depending on the total volume to be infused. Blood samples were
      obtained over a 6-week period to assess pharmacokinetics, immunogenicity, and the
      pharmacodynamic effects on leukocytes and TNF-alpha. A blood sample was taken at
      6 months for a viral safety check. Administrations were generally well tolerated
      with only one reference IVIG infusion stopped prematurely due to headache. The
      IgG Cmax and AUC over the 6-week blood sampling period from both test
      formulations satisfied equivalence criteria compared with the reference
      formulation. In subjects receiving IVIG-L, peak concentrations of the stabilizer
      nicotinamide ranged from 0.34 to 0.47 mmol/L and of nicotinamide-N-oxide from
      0.03 to 0.04 mmol/L, which are below those reported to cause adverse events.
      During the infusion of IVIG, leukocyte counts initially declined from a baseline
      of 5.7 +/- 1.1 x 10(9)/L to 3.7 +/- 0.8 x 10(9)/L at 2 to 4 hours and returned to
      baseline by 24 hours. TNF-alpha levels, reflecting activation of the monocyte
      macrophage system by the infused IVIG, rose from a baseline of 13 +/- 4 pg/mL to
      a peak of 272 +/- 324 pg/mL at 2 to 4 hours and returned to baseline by 24 hours.
      These patterns were generally similar for the test formulations, with the
      exception that the increase in TNF-alpha levels was dampened for IVIG-N, although
      this was not statistically significant. There was no evidence of immunogenicity
      or viral transmission from any of the formulations. Hence, these three
      formulations were generally well tolerated, yielded similar systemic exposure to
      IgG over a 6-week period after administration, and did not give rise to
      immunogenicity or viral safety concerns.

PMID- 10883414
TI  - Modeling of circadian testosterone in healthy men and hypogonadal men.
AB  - The testosterone circadian rhythm has been reported extensively in the literature
      and has been described by a cosine function. Typically, these data are measured
      at frequent and regular (e.g., hourly) intervals. However, modeling circadian
      rhythm with data collected sparsely at irregular intervals and/or data that are
      not collected at the same time in all individuals has not been reported. The
      population nonlinear mixed-effects approach can handle such data and also allows
      covariates to be incorporated into the model. Frequent hourly testosterone
      concentration data available in the literature for young and elderly healthy
      volunteers were analyzed first. In the elderly, blunted or completely absent
      circadian rhythm has been reported, but a full circadian model was significantly
      better than a model containing one or no circadian component. Therefore, data
      from both the elderly and young were modeled together, and age was included as a
      categorical variable (young or elderly). Consistent with literature, the rhythm
      adjusted mean testosterone concentrations was lower, and the deviation from the
      mean, especially to the maximum daily value, was less than half in the elderly
      (7%) compared to young subjects (16%). The testosterone concentration data
      measured infrequently and at varying intervals in young normal men and
      hypogonadal men were evaluated next. Although not measured at regular frequency
      in each individual, the data were obtained at different clock times for different
      subjects. Since for population mixed-effects analysis, data from all subjects are
      pooled, there was enough information to profile the 24-hour circadian cycle. In
      healthy young subjects, the mean Cnadir, Cpeak, Tnadir, and Tpeak values
      estimated from the model were 420 ng/dL, 577 ng/dL, 21:42 hours, and 0600 hours,
      respectively, and were similar to the parameters obtained for the frequently
      sampled young subjects. In hypogonadal men (testosterone concentrations < 300
      ng/dL), the mean testosterone concentrations were much lower than the healthy
      young or elderly men, and a straight-line model was the best descriptor (i.e., no
      circadian rhythm was detected). It was also shown that with the application of a
      transdermal testosterone system, the mean testosterone concentrations in the
      treated men were within the 95% confidence interval for healthy young men. The
      results presented here suggest that the advantages of the analysis approach-
      namely, handling of covariates and handling of sparse, infrequently collected
      data--can be used in characterizing testosterone circadian rhythm or the lack of
      it.

PMID- 10883415
TI  - The influence of the menstrual cycle on triazolam and indocyanine green
      pharmacokinetics.
AB  - The aim of this study was to investigate the effects of the menstrual cycle phase
      on the pharmacokinetics of two high-clearance agents, triazolam and indocyanine
      green (ICG). Eleven nonsmoking, healthy, eumenorrheic women were enrolled in this
      study. Triazolam (0.25 mg) was administered orally, and indocyanine green was
      administered as an i.v. bolus (0.5 mg/kg) during the follicular, ovulatory, and
      luteal phases of a single menstrual cycle. Blood samples were collected over 10
      hours for triazolam and over 30 minutes for ICG. Triazolam and indocyanine green
      concentrations were quantitated by electron capture gas chromatography and
      spectrophotometry, respectively. Noncompartmental analysis was used to determine
      relevant pharmacokinetics parameters, which were statistically assessed using two
      way ANOVA (p < 0.05). No statistical differences for triazolam were observed.
      Vd/F was lower in the luteal phase (107 L) as compared to the follicular (138 L)
      and ovulatory (133 L) phases. Clearance of triazolam was comparable in the
      follicular (583 ml/min), ovulatory (565 ml/min), and luteal (538 ml/min) phases.
      ICG also revealed no significant differences across the phases. These results
      suggest that the phases of the menstrual cycle do not influence triazolam or ICG
      pharmacokinetics.

PMID- 10883416
TI  - Pharmacokinetics and safety of single intravenous infusions of the adenosine
      agonist, AMP 579, in patients with end-stage renal insufficiency.
AB  - The pharmacokinetics of an adenosine agonist (AMP 579) were characterized in
      patients with end-stage renal disease compared to sex- and age-matched healthy
      volunteers. All study participants were administered single AMP 579 doses of 50
      micrograms/kg as a 6-hour, constant-rate intravenous infusion. Serial blood
      samples were obtained for measurement of plasma AMP 579 concentration, and
      predose samples were collected for determination of AMP 579 plasma protein
      binding. The safety of AMP 579 administration in renally impaired patients also
      was evaluated. AMP 579 was rapidly cleared from the systemic circulation in all
      subjects as plasma concentrations were below the limit of detection by 2 to 4
      hours after terminating the infusion. Noncompartmental analysis yielded mean
      values for the plasma AMP 579 concentration at the end of the 6-hour infusion (C6
      h) of 9.6 and 10.5 ng/mL and for systemic clearances (Cl) of 0.91 and 0.72 L/h/kg
      in renally impaired patients and healthy volunteers, respectively. Mean volumes
      of distribution (Vss) in the renally impaired and healthy volunteers were 0.92
      and 0.84 L/kg, and terminal elimination half-life values (t1/2) were 1.61 and
      1.33 hours, respectively. The extent to which AMP 579 is bound to plasma protein
      was not altered in renally impaired patients since the free fractions were 4.0%
      and 3.4% for renally impaired and healthy volunteers, respectively. It was
      concluded that the pharmacokinetic parameters of AMP 579 were similar in both
      groups. The 6-hour AMP 579 infusion was generally well tolerated by both renal
      patients and healthy volunteers. There were no serious adverse events, and there
      were only two mild adverse events in 1 renally impaired patient judged possibly
      related to the study drug that quickly resolved. There were no clinically
      significant changes in laboratory values or clinical evaluations during the
      study. There was a slight increase in heart rate during the infusion of similar
      magnitude for both the renal patients and healthy volunteers. These data suggest
      that AMP 579 may be administered to renally impaired patients with minimal
      cardiovascular effects and adverse events. These results in end-stage renal
      patients (worst-case scenario) indicate that dose adjustment in patients with
      renal insufficiency of any degree is not indicated in future studies of AMP 579.

PMID- 10883417
TI  - Pharmacokinetic/pharmacodynamic evaluation of a novel potassium channel opener,
      SKP-450, in healthy volunteers.
AB  - To evaluate the pharmacokinetic/pharmacodynamic characteristics of SKP-450, a
      novel K+ channel opener, a single blind, randomized, placebo-controlled, dose
      rising, parallel-group study was conducted in 28 healthy volunteers. The
      volunteers were randomly allocated to dosage groups of 50 micrograms, 100
      micrograms, 200 micrograms, and 300 micrograms. Single doses of SKP-450 were
      administered orally, after overnight fasting, and serial blood sampling and
      pharmacodynamic measurements were performed up to 48 hours after the drug was
      administered. The 200 micrograms group was further studied for food interactions
      in a crossover fashion. Drug concentrations in plasma were determined by HPLC.
      Hemodynamic changes after drug administration were evaluated by serial
      measurements of blood pressure (BP), pulse rate (PR), cardiac index (CI), and
      total peripheral resistance (TPR), using computerized impedance cardiography.
      Changes in plasma renin activity (PRA) and aldosterone concentrations (PAC) were
      determined 4 and 24 hours after drug administration. Both SKP-450 and SKP-818, an
      active metabolite, showed linear pharmacokinetic characteristics, and food intake
      did not significantly affect the pharmacokinetic characteristics of either
      compound. Dose-related pharmacological effects were obvious for both the 200
      micrograms and 300 micrograms groups. Hemodynamic parameters related to
      vasodilation and reflex tachycardia, such as maximum changes in diastolic BP, PR,
      CI, and TPR, showed significant dose-dependent changes. The area under the time
      effect curve (AUEC) of the parameters also showed a similar dose-dependent
      pattern. The PRA and PAC exhibited significant changes 4 hours after drug
      administration in the 300 micrograms group. Adverse effects, such as headaches,
      were more frequently observed at the higher dose levels. SKP-450 was generally
      well tolerated by these normotensive subjects. The antihypertensive efficacy of
      SKP-450 needs to be evaluated in hypertensive patients after multiple dosing.

PMID- 10883418
TI  - Lack of effect of a high-fat meal on the bioavailability of 17 beta
      estradiol/norgestimate in healthy postmenopausal women.
AB  - The effect of a high-fat meal on the absorption and pharmacokinetics of 17 beta
      estradiol (E2), estrone (E1), estrone sulfate (E1S), and 17-deacetylnorgestimate
      (17d-NGM) were determined in this two-way complete crossover study of a single
      dose of E2/NGM (2 mg/180 micrograms) in 24 postmenopausal women. Equal numbers of
      subjects were randomly assigned to two treatment sequences indicated by the order
      of fed and fasting treatments. Serial blood samples were collected before and
      after dosing and assayed using validated methods. Food had no effect on the
      pharmacokinetics of E2, the pharmacologically active estrogen species. Food
      increased the rates of formation of E1 and E1S and slowed the formation of 17d
      NGM. However, because E1 and E1S are pharmacologically less active metabolites of
      E2, and since the pharmacokinetic alterations in 17d-NGM were observed over a
      short time period, these results are probably of no clinical relevance. The
      extent of formation of all analytes, as measured by AUC, was not affected by
      food. In conclusion, administration of a tablet containing 17 beta
      estradiol/norgestimate (2 mg/180 micrograms) was safe and well tolerated by
      healthy postmenopausal women and may be given without regard to the timing of
      meals in relation to dosing.

PMID- 10883419
TI  - A mass balance study to evaluate the biotransformation and excretion of [14C]
      triamcinolone acetonide following oral administration.
AB  - The principle objective of this study was to characterize the absorption,
      metabolism, and disposition of orally administered [14C]-triamcinolone acetonide.
      Six healthy male subjects each received a single 100 microCi (approximately 800
      micrograms) oral dose of [14C]-triamcinolone acetonide. Plasma, urine, and fecal
      samples were collected at selected times and analyzed for triamcinolone acetonide
      and [14C]-derived radioactivity. Plasma protein binding of triamcinolone
      acetonide was also determined. Metabolite profiling and identification were
      carried out in plasma and excreta. Principle metabolites were assessed for
      activity with in vitro anti-inflammatory models. [14C]-triamcinolone acetonide
      was found to be systemically absorbed following oral administration. The
      presystemic metabolism and clearance of triamcinolone acetonide were extensive,
      with only a small fraction of the total plasma radioactivity being made up of
      triamcinolone acetonide. Little to no parent compound was detected in the plasma
      24 hours after administration. Most of the urinary and fecally [14C]-derived
      radioactivity was also excreted within 24 and 72 hours postdose, respectively.
      Mean plasma protein binding of triamcinolone acetonide was constant, predictable,
      and a relatively low 68% over a 24-fold range of plasma concentrations. Three
      principle metabolites of triamcinolone acetonide were profiled in plasma, urine,
      and feces. These metabolites were identified as 6 beta-hydroxy triamcinolone, 21
      carboxylic acid triamcinolone acetonide, and 6 beta-hydroxy-21-oic triamcinolone
      acetonide. All three metabolites failed to show any concentration-dependent
      effects in anti-inflammatory models evaluating IL-5-sustained eosinophil
      viability and IgE-induced basophil histamine release.

PMID- 10883420
TI  - The absolute bioavailability of oral melatonin.
AB  - The absolute bioavailability of oral melatonin tablets was studied in 12 normal
      healthy volunteers. Subjects were administered, in a randomized crossover
      fashion, melatonin 2 mg intravenously and 2 and 4 mg orally. Blood was sampled
      over approximately eight (estimated) half-lives. Both the 2 and the 4 mg oral
      dosages showed an absolute bioavailability of approximately 15%. No difference in
      serum half-life was seen in any of the study phases. Oral melatonin tablets in
      dosages of 2 and 4 mg show poor absolute bioavailability, either due to poor oral
      absorption, large first-pass metabolism, or a combination of both. Further
      studies examining larger doses, in an attempt to saturate first-pass metabolism
      if it occurs, may be warranted.

PMID- 10883421
TI  - How reliable are measurements with arthrometers?

PMID- 10883422
TI  - EMG biofeedback assisted KT-1000 evaluation of anterior tibial displacement.
AB  - Two studies were undertaken to evaluate the use of EMG biofeedback to encourage
      hamstring relaxation during KT-1000 measurement of anterior tibial displacement.
      In study 1, 60 ACL-deficient patients were studied in three groups using 15 lb
      and 20 lb in each group: in group 1 the patients were simply retested 15 min
      after the initial test sequence, in group 2 they were initially retested with EMG
      biofeedback and then again without, and in group 3 they were retested twice with
      EMG biofeedback. No significant difference in mean anterior tibial displacement
      was seen between the initial measurements and retest measurements when no EMG
      biofeedback was used. A significant increase in mean anterior tibial displacement
      was seen when the retesting was performed with EMG biofeedback. No further
      increase was seen with repeated retesting with EMG biofeedback. In study 2, 40
      patients were evaluated 4-12 months following ACL reconstruction. KT-1000
      measurements of anterior tibial displacement of both the operated and non
      operated knees were made at 15 lb and 30 lb with and without the use of EMG
      biofeedback. EMG biofeedback was associated with a significant increase in
      unilateral measurement of anterior tibial displacement. When side-to-side
      differences were compared, there was a small but statistically significant
      increase in anterior tibial displacement with the use of EMG biofeedback.
      Although the use of EMG biofeedback to encourage hamstring relaxation does
      increase unilateral measurements of anterior tibial displacement, it does not
      appear to have a clinically significant effect on measurement of side-to-side
      difference. It may have a role in testing patients who have difficulty achieving
      hamstring relaxation or in aiding inexperienced examiners.

PMID- 10883423
TI  - Abnormal bone scans in anterior cruciate ligament deficiency indicate structural
      and functional abnormalities.
AB  - Many patients with anterior cruciate ligament (ACL) deficiency have an abnormal
      bone scan. This finding has not yet been explained. Suggested explanations
      include intra-articular (structural) or kinematic (functional) abnormalities. We
      examined the relationship between bone scintigraphy and cartilage degeneration or
      meniscal lesions in the ACL-deficient knee in 95 consecutive patients who had
      bone scintigraphy 1-3 days prior to arthroscopic ACL reconstruction. Intra
      articular abnormalities of the knee did not explain all scintigraphic patterns of
      this study. We did not find clinically useful positive predictive values for
      scintigraphic patterns considered to indicate cartilage degeneration or a lateral
      meniscus lesion. A clinically useful positive predictive value was found only for
      medial meniscus lesions when time since ACL rupture was more than 18 months, and
      for local cartilage degeneration when markedly increased uptake was seen when
      time since ACL rupture was more than 4 months. Considering these findings,
      alternative explanations are discussed, based on specific aspects of abnormal
      kinematics and adaptive bone metabolism of the ACL-deficient knee.

PMID- 10883424
TI  - The effect of knee position on the reproducibility of measurements taken from
      stress films: a comparison of four measurement methods.
AB  - We evaluated the accuracy of four different means of radiographic measurement of
      anteroposterior translation in the knee joint. The tests were performed in normal
      knees, in knees lacking the anterior cruciate ligament, and in knees lacking both
      anterior and posterior cruciate ligaments; the knees were obtained from cadavers.
      It is difficult to define landmarks and to perform exact measurements, and we
      sought to determine which of the four methods is the most accurate. In
      particular, we examined the effect of various degrees of rotation and flexion on
      the positional relationships of the landmarks of the tibia and the femur.

PMID- 10883425
TI  - A new positioning device for precise femoral insertion of the anterior cruciate
      ligament autograft.
AB  - Optimal anatomical replacement of anterior cruciate ligament (ACL) is essential
      for achieving knee stability. Several methods for localizing a correct center of
      femoral insertion of the ACL graft and identifying a center of the femoral tunnel
      have been proposed, including free-hand drilling with "eyeballing," the use of
      tensiometers or isometers, fluoroscopic or radioscopic control, and aiming
      devices. We present a new positioning device for precise femoral insertion of the
      ACL autograft based on preoperative radiographic measurements (quadrant method)
      for locating the femoral ACL insertion. The aim was to find the best placement in
      the individual knee considering the wide variations among individuals and to
      decrease the likelihood of the surgeon making a mistake in localizing the optimal
      position of femoral insertion of the ACL. In comparison to other positioning
      procedures this method provides an exact preoperative planning of femoral
      insertion of the ACL and eliminates numerous sources of errors.

PMID- 10883426
TI  - The Oxford unicompartmental knee prosthesis: a 5-year follow-up.
AB  - We present our medium-term results with the Oxford unicompartmental knee
      prosthesis for unicompartmental osteoarthrosis. After an average of 58 months the
      mean on the Hospital for Special Surgery knee score in 38 medial and 3 lateral
      prostheses (39 patients) was 87. There were three revisions; in the remaining 36
      patients the results were: 29 excellent, 3 good, 2 moderate, and 2 poor. In two
      of the three revisions and in two of the four poor and moderate results, the
      indications for the procedure were debatable. Our findings confirm the good
      results reported in other studies and underline the importance of adhering to
      strict indications to reduce the number of poor results.

PMID- 10883427
TI  - Technical innovation: creation of a peripheral vascularized trough to enhance
      healing in cryopreserved meniscal allograft reconstruction.
AB  - The important functions of the meniscus have been well described. Lack of a
      meniscus may lead to instability and early osteoarthrosis of the knee. Meniscal
      transplantation is an option following complete or subtotal meniscectomy in
      symptomatic patients with correct alignment, and mild to moderate chondrosis with
      the goal of preventing further degenerative sequelae to the knee. Since the first
      meniscus allograft implantation was performed 1984, there have been reported
      several open and arthroscopic techniques. We present our technique of
      arthroscopically assisted transplantation of a cryopreserved meniscal allograft
      with special consideration given to the technical details of this procedure. This
      technique employs creation of a circumferential osseocancellous trough in
      combination with transosseous tibial tunnel fixation and arthroscopic suture
      passage to both secure and enhance healing of the meniscal allograft.

PMID- 10883428
TI  - Peroneal nerve palsy following knee dislocation: pathoanatomy and implications
      for treatment.
AB  - Peroneal nerve palsy following knee dislocation is a serious problem, and
      neurolysis at the time of knee reconstruction does not always result in return of
      peroneal nerve function. We describe peroneal nerve pathoanatomy in three
      patients in whom late exploration of the peroneal nerve was performed because of
      ongoing absence of ankle dorsiflexion. We identified frank nerve rupture in two
      patients and a lengthy neuroma in continuity in one which extended far proximal
      to the fibular head and well above the previous surgical incision used for
      peroneal nerve neurolysis at the time of knee reconstruction. In light of the
      current state of microneural surgery and the potential to reconstruct nerve
      defects, we discuss how our findings impact on treatment, and provide
      recommendations which may improve recovery of peroneal nerve function in future
      cases.

PMID- 10883429
TI  - Endoscopic carpal tunnel release: results with special consideration to possible
      complications.
AB  - Single-portal endoscopic carpal tunnel release (Agee technique) was carried out
      in 148 patients. Of these, 100 were examined clinically and
      electrophysiologically 1 day before surgery and 1 and 3 months thereafter. Ten
      patients experienced transient ulnar neuropraxia and two patients complained
      postoperatively of intense pain in the middle and ring fingers. Three patients
      suffered residual symptoms. In one of these an incomplete release of the distal
      portion of the retinaculum flexorum was suspected and later confirmed by magnetic
      resonance imaging. Another patient had applied for pension due to problems
      associated with a vertebral fracture in addition to his carpal tunnel symptoms. A
      third patient with residual symptoms was rheumatic, and upon reexamination 6
      months later he was virtually symptom free. Five of the 148 operations were
      converted to an open procedure due to poor visualization. A review of literature
      on carpal tunnel release (biportal Chow technique and uniportal Agee technique)
      uncovered 31 intra- and postoperative complications, including 14 affecting nerve
      structures, 2 tendon structures, 2 bony structures, and 9 the surrounding
      tissues. We discuss the most common complications, considering in particular the
      anatomical characteristics in the carpal tunnel region.

PMID- 10883430
TI  - Anatomical reconstruction versus tenodesis for the treatment of chronic
      anterolateral instability of the ankle joint: a 2- to 10-year follow-up,
      multicenter study.
AB  - The clinical outcome of anatomical reconstruction or tenodesis in the treatment
      of chronic anterolateral ankle instability was assessed in a retrospective
      multicenter study. The anatomical reconstruction group (group A) consisted of 106
      patients (mean age at operation 24 +/- 8.4 years) and the tenodesis group (group
      B) of 110 patients (mean age at operation 26 +/- 11.4 years). Patients were
      evaluated at a mean follow-up of 5.5 +/- 2.8 years in group A and 5.2 +/- 2.9
      years in group B. The review protocol included patient characteristics, physical
      examination, two ankle scoring scales to evaluate the functional results, and
      standard anteroposterior and lateral radiographs to evaluate degenerative
      changes. Mechanical stability was evaluated using standardized stress
      radiographs. A larger number of reoperations was performed in group B (P =
      0.008). At physical examination, more patients in group B had a smaller range of
      ankle motion than those in group A (P = 0.009). A larger proportion of patients
      in group B had medially located osteophytes, as seen on standard radiographs (P =
      0.04). On stress radiographic examination, the mean talar tilt (P = 0.001) and
      mean anterior talar translation (P < 0.001) were seen to be significantly greater
      in group B than in group A. There were no differences in mean Karlsson score
      between the groups, but more patients in group A had an excellent result on the
      Good score (P = 0.011). Unlike anatomical reconstructions, tenodeses do not
      restore the normal anatomy of the lateral ankle ligaments. This results in
      restricted range of ankle motion, reduced long-term stability, an increased risk
      of medially located degenerative changes, a larger number of reoperations, and
      less satisfactory overall results.

PMID- 10883431
TI  - The reliability of balance tests performed on the kinesthetic ability trainer
      (KAT 2000).
AB  - The Kinesthetic Ability Trainer (KAT 2000) is a balance platform designed for
      training and functional testing of the neuromuscular control system. Forty
      healthy and sports-active persons were tested and 1 month later retested to
      investigate the reliability of the KAT 2000 testing "one-leg static balance" and
      "two-leg dynamic balance". A significant improvement at retesting on the same day
      was seen in both tests; furthermore the dynamic test result improved
      significantly with retesting 1 month later. The data obtained made it possible to
      calculate the 95% confidence limits for an unchanged test result for a single
      person and a group of persons. The results show a clear learning effect when the
      persons are retested, especially in the dynamic test. The KAT 2000 can be used as
      a tool for testing groups of persons both in short- and long-term studies, but it
      cannot be used for testing single persons due to the great variance in the test
      results. Further investigations involving injured persons are needed to determine
      the range of improvement after intervention.

PMID- 10883432
TI  - Spinal cord injury without radiographic abnormalities in children and
      adolescents: case report of a severe cervical spine lesion and review of
      literature.
AB  - The biomechanics of the child's and juvenile's spine is responsible for the
      commonly encountered closed spinal trauma with significant neurological injury
      but without bony or ligament injury (particularly of the cervical spine). The
      ligamentous laxity and hypermobility of the young bony cervical and thoracic
      spine predispose to spinal cord injury without radiographic abnormalities. We
      report a 16-year-old girl with typical features of this type of injury after a
      "flic-flac" sports injury. We conclude that children and adolescents who have
      neurological deficits without positive radiographic findings require appropriate
      diagnostic screening, monitoring, and often a prolonged therapy. The sometimes
      changing neurological deficits should never be ignored or dismissed as
      psychogenic affection.

PMID- 10883433
TI  - Experimental photodynamic laser therapy for rheumatoid arthritis with a second
      generation photosensitizer.
AB  - Photodynamic laser therapy has been shown to be a new method for the treatment of
      synovitis in various animal models. Its principle is the accumulation of a
      photosensitizing drug in the inflamed synovium which is destroyed by
      photoactivation of the drug. In the present animal study we demonstrate the
      effect of a second-generation photosensitizer and suggest a concept for light
      dosimetry within the joint. We used 38 inbred rabbits for the IgG-induced
      arthritis model; 2 mg/kg of the benzoporphyrin derivative monoacid ring-A (BPD
      MA) Verteporfin were administered 3 h before irradiation, which was performed
      using a 690-nm diode laser coupled to quartz glass fiber with a cylinder diffusor
      tip at a total light energy of either 180 or 470 J. During irradiation specific
      fluorescence of BPD-MA was monitored using a spectroscopy unit. The effect of the
      photodynamic laser therapy was documented grossly and histologically after 1
      week. Within the 470 J-group a complete necrosis of the inflamed synovium was
      observed. The bradytrophic structures of the joint, however, remained unchanged.
      Throughout the 180 J-group the extent of necrosis was minor. During irradiation
      the tissue fluorescence of BPD-MA showed a dose-dependent decrease. Using BPD-MA
      as a photosensitizer a highly selective and minimal invasive synoviorthesis can
      be performed. At a dose of 2 mg/kg the histological effect depends on the light
      dose. For optimum efficacy a total energy of 470 J seems favorable. Online
      fluorescence detection can be used to monitor the effect of light administration.
      For dosimetry therefore an online tissue fluorescence detection may represent a
      technical solution.

PMID- 10883434
TI  - Periodic patterns in biology.
AB  - New physical and computerized techniques for continuous read-out of intra and
      intercellular signals allow the study of biochemical dynamics of both local and
      spreading modes. A vast amount of new information in the area of periodic,
      quasiperiodic, and chaotic reactions is currently being accumulated, some of
      which is reviewed here to provide typical mechanisms and occurrences on the basis
      of a wide variety of reaction circuits and target structures. Following a short
      review of the time windows of temporal pattern, mechanisms and models of period
      generating and transmitting systems are presented for both calcium and oligogenic
      oscillations. Spreading mechanisms of local signal oscillations through intra-
      and intercellular space yielding periodic patterns are presented for calcium
      waves in Dictyostelium discoideum, of cardiovascular and neuronal networks,
      followed by consideration of some of the properties of complex systems behavior.

PMID- 10883435
TI  - Red legs and golden gasters: Batesian mimicry in Australian ants.
AB  - There are numerous reports of invertebrates that are visual mimics of ants, but
      no formal reports of mimicry of an ant, by an ant. Two endemic Australian ants,
      Myrmecia fulvipes and Camponotus bendigensis are remarkably similar in colour and
      size; both are generally black but have red legs and golden gasters. The density
      and hue of the pubescence of each ant's gaster are relatively uncommon in ants,
      but are very rare when combined with the black forebody and red legs. The ants
      are similarly sized but are smaller than other species closely related to M.
      fulvipes. The range of C. bendigensis lies entirely within that of M. fulvipes,
      and both species excavate ground nests in open woodland. Finally, workers of both
      species are crepuscular and forage solitarily. These data suggest that the
      relatively benign formicine C. bendigensis is a Batesian mimic of the formidable
      myrmeciine M. fulvipes.

PMID- 10883436
TI  - The effect of a green leaf volatile on host plant finding by larvae of a
      herbivorous insect.
AB  - The role of a general green leaf volatile (glv) in host finding by larvae of the
      oligophagous chrysomelid Cassida denticollis was investigated using a new
      bioassay which takes into account the need for neonate larvae of this species to
      climb fresh host plants from the ground. A "stem arena" was designed in which
      plant stems of the host, tansy (Tanacetum vulgare), and stem dummies (tooth
      picks), both wrapped in perforated filter paper, were offered to neonate larvae.
      The wrapping allowed olfactory responses to be tested by preventing access to
      contact stimuli of stems and dummies. Larvae significantly preferred to climb the
      wrapped tansy stems over dummies after a period of 15 min. The test glv, (Z)-3
      hexen-1-ol, was not attractive when applied to dummies. However, when the glv was
      applied to the bottom of the arena, the ability of larvae to discriminate between
      host stems and untreated dummies was significantly enhanced. More larvae climbed
      wrapped host stems than dummies even within 5 min. While numerous other
      herbivorous insects are known to be directly attracted by glv, this study shows
      that a singly offered glv on its own is unattractive to an herbivore but enhances
      the herbivore's ability to differentiate between host and nonhost plants.

PMID- 10883437
TI  - Origin of the Henze solution/precipitate from morula cells of the blood of the
      ascidian Phallusia mammillata.
AB  - The "Henze solution", derived originally from the aqueous extraction of pelleted
      whole blood from the ascidian Phallusia mammillata, was examined using spectral
      studies. The aqueous extraction of fractionated blood cells including compartment
      cells, signet ring cells, and morula cells obtained using cell separation
      techniques were also examined. It was found that this Henze solution, and the
      Henze precipitate itself derived from this solution, emanated solely from the
      morula cells. Furthermore, it was found that this solution is formed
      independently of the vanadium metal ions otherwise associated with the
      vanadocytes. Observation of the Henze precipitate by light microscopy shows that
      this material partially forms crystallites or microglasses.

PMID- 10883438
TI  - First observation of different diffusion coefficients for two conformers in a
      neat liquid.
AB  - Self-diffusion coefficients were studied for the highly polar liquid N
      methylformamide at pressures up to 200 MPa between the melting pressure curves
      and 420 K by the spin-echo method. N-Methylformamide exists as a mixture of two
      conformers in the neat liquid. These conformers have large differences at lower
      temperatures in their dynamic and structural properties. The self-diffusion
      coefficient of the cis-conformer being 17% lower than that of the trans-conformer
      at the same T and p. This is the first observation of such an effect. The
      experimental study is supported by Monte Carlo (MC) calculations which show that
      the first neighbors around a cis conformer are arranged differently than in an
      all trans liquid. The difference leads in the simulations to a much lower
      dielectric constant for the trans-cis mixture and might also explain the
      retardation of diffusion for the cis conformer.

PMID- 10883439
TI  - Fever in honeybee colonies.
AB  - Honeybees, Apis spp., maintain elevated temperatures inside their nests to
      accelerate brood development and to facilitate defense against predators. We
      present an additional defensive function of elevating nest temperature: honeybees
      generate a brood-comb fever in response to colonial infection by the heat
      sensitive pathogen Ascosphaera apis. This response occurs before larvae are
      killed, suggesting that either honeybee workers detect the infection before
      symptoms are visible, or that larvae communicate the ingestion of the pathogen.
      This response is a striking example of convergent evolution between this
      "superorganism" and other fever-producing animals.

PMID- 10883440
TI  - Pigeon orientation: effects of the application of magnets under overcast skies.
AB  - To verify the existence of a magnetic compass in birds, researchers have often
      released homing pigeons under overcast skies that are equipped with bar magnets
      on various parts of their body. In particular, Keeton was successful in finding
      disorientation in overcast conditions in a first series of tests, but not in a
      second series. The experiments reported here attempt to explain this
      contradiction on the basis of findings obtained by releasing pigeons equipped in
      a way similar to that reported in Keeton's tests and pigeons equipped in a way
      similar to that reported by other authors.

PMID- 10883441
TI  - Fungal spore germination into yeast or mycelium: possible implications of
      dimorphism in evolution and human pathogenesis.
AB  - The ability of dimorphism in fungi is conventionally regarded as a reversible
      change between the two vegetative forms, yeast and mycelium, in response to
      environmental change. A zygomycetous isolate, Benjaminiella poitrasii, exhibited
      yeast-mycelium transition in response to the change in temperature (37-28 degrees
      C) and decrease in glucose concentration. For the first time the presence of
      dimorphic response during asexual and sexual spore germination is reported under
      the dimorphism-triggering conditions in B. poitrasii. The zygospores germinated
      into budding yeast when subjected to yeast-form supporting conditions. The
      mycelium-form favoring conditions gave rise to true mycelium. Similarly, the
      asexual spores displayed a dimorphic response during germination. Our
      observations suggest that dimorphism is an intrinsic ability present in the
      vegetative, asexual, and sexual forms of the fungus. As dimorphic fungi are
      intermediate to the unicellular yeast and the filamentous forms, understanding of
      the dimorphic character could be useful to trace the evolutionary relationships
      among taxonomically different fungi. Moreover, the implications of spore
      germination during the onset of pathogenesis and in drug development for human
      health care are discussed.

PMID- 10883442
TI  - Debris removal by head-pushing in A. florea Fabr. honeybees.
AB  - The nest of the dwarf honeybee A. florea Fabr. consists of a single comb attached
      to a tree branch. Recruitment dances take place on the upper surface of the comb
      that must therefore be kept clear of debris. We report here, for the first time,
      a behaviour that serves for removing leaves and other foreign objects from the
      surface of the comb. Individual workers crawl under the object and lift it with
      their heads, pushing it towards the rim where it eventually slides off the comb.
      Objects that are heavier or fixed at one end such as leaves are nevertheless
      lifted and kept away from the surface for up to several minutes. This "head
      pushing" is frequently performed without the aid of mandibles, and individuals
      performing it maintain a distinctive posture, holding the forelegs at an angle
      without touching the object. Repeated involvement of particular individuals
      indicate that head-pushers might form a distinct task group.

PMID- 10883443
TI  - Cytogenetic and molecular genetic techniques as adjunctive approaches in the
      diagnosis of bone and soft tissue tumors.
AB  - Important and meaningful advances have been made in mesenchymal tumor
      cytogenetics during the last two decades. A number of bone and soft tissue tumors
      have been shown to have recurrent, if not specific, chromosomal changes,
      particularly translocations. These changes not only serve as aids in the
      diagnosis and classification of bone and soft tissue tumors, especially in the
      differential diagnosis of those of confusing nature, but have also guided
      molecular studies in establishing the underlying genes involved. To date, a
      number of tumor-specific gene fusions have been identified and many have been
      shown to encode aberrant transcription factors. These key biological events in
      bone and soft tissue tumors are crucial not only to our understanding of the
      sarcomagenetic processes leading to the various tumors, but also ultimately in
      the design of specific therapies tailored to the genetic events in mesenchymal
      neoplasms.

PMID- 10883444
TI  - Sonographic appearance of nonoperatively treated Achilles tendon ruptures.
AB  - OBJECTIVE: This report describes the gray-scale and color Doppler sonographic
      appearance of healed Achilles tendon ruptures that have been treated
      nonoperatively. DESIGN AND PATIENTS: Eleven patients with acute Achilles tendon
      ruptures were studied with sonography in the acute setting and following
      nonoperative management of their torn tendon. RESULTS: On sonographic
      examination, healed tendons treated nonoperatively are characterized by mild
      residual distortion of the normal fibrillar architecture of the tendon, anterior
      bulging or irregularity of the healed tendon, and a hypoechoic area about the
      site of rupture. Less frequent observations include mildly increased color flow
      and calcification at the rupture site. The previously described findings of acute
      tears, including hematomas, gaps at the rupture site, hyperemic torn tendon ends,
      and markedly distorted fibrillar architecture, were seen to have resolved in this
      series. CONCLUSION: The Achilles tendon tear treated nonoperatively has a
      different sonographic appearance from that of a normal or acutely ruptured
      tendon.

PMID- 10883445
TI  - Patient perception of magnetic resonance arthrography.
AB  - OBJECTIVE: Magnetic resonance (MR) arthrography has been demonstrated to be more
      accurate than MR imaging alone in the identification of a variety of
      musculoskeletal pathology. While the complication rate of intra-articular
      gadolinium: saline injection has been shown to be relatively low, MR arthrography
      is more invasive, painful, and costly, and less convenient, than MR imaging
      alone. The purpose of this study was to evaluate patients' perception of the fear
      and discomfort, and to assess their overall acceptance of the intra-articular
      gadolinium injection. DESIGN AND PATIENTS: Between October 1997 and January 1998,
      113 outpatients who were referred to Yale-New Haven Hospital for MR arthrography
      of the ankle, elbow, hip, knee, shoulder, or wrist were asked to complete a
      questionnaire rating their fear of factors most commonly associated with the
      procedure including "pain", "needles", "complications", and "discovery of results
      that would lead to surgery". In addition, after having undergone the intra
      articular gadolinium:saline injection, patients were asked to rate their
      perception of pain. RESULTS: While many patients expressed fear of "pain" and
      "needles", after having undergone the injection their overall pain rating score
      was low. Only 6% actually found gadolinium arthrography more painful than
      expected. CONCLUSION: Despite the fact that patients expressed apprehension about
      certain aspects of MR arthrography, subjects who underwent the intra-articular
      gadolinium injection considered the discomfort less than expected. Clinicians
      should not hesitate to order MR arthrography because the accuracy of the
      procedure is high enough that patients accept the discomfort.

PMID- 10883446
TI  - Unsuspected metastases presenting as solitary soft tissue lesions: a fourteen
      year review.
AB  - OBJECTIVE: To describe a series of patients with no known primary malignancy who
      presented with a solitary unsuspected soft tissue metastasis masquerading as a
      soft tissue sarcoma, and secondarily to describe the imaging appearance of these
      lesions. DESIGN: Records of two academic hospitals with active orthopedic
      oncology services were reviewed for patients meeting the above criteria. Clinical
      charts were examined, and the imaging appearance of the soft tissue lesions
      retrospectively reviewed. PATIENTS: Of 1421 patients examined for soft tissue
      lesions, 11 were found who met the above criteria. RESULTS: Of the 11 patients
      whose initial presentation was a solitary soft tissue metastasis, eight were
      found to have a primary lung cancer, two were diagnosed with adenocarcinoma of
      unknown primary, and adenocarcinoma of the colon was discovered in the remaining
      patient. CONCLUSIONS: The clinical presentation of a solitary soft tissue
      metastasis without a known primary malignancy is a rare occurrence, with an
      incidence of approximately 0.8%. Lung cancer is the primary neoplasm in a high
      percentage of these cases.

PMID- 10883447
TI  - Rapid chondrolysis after an intra-articular leak of bone cement in treatment of a
      benign acetabular subchondral cyst: an unusual complication of percutaneous
      injection of acrylic cement.
AB  - Percutaneous injection of methylmethacrylate is now increasingly employed to
      treat bone lesions, both malignant and benign. However, the risks of this
      procedure are still to be fully established. In this report, we describe a case
      of rapid chondrolysis appearing after the intra-articular leakage of cement
      during injection of an acetabular subchondral cyst, resulting in hip replacement.
      Although the mechanism of such chondrolysis is unknown, this event suggests a
      chondrolytic effect of the acrylic cement. Thus, it is essential to
      systematically search for the presence of an intra-articular passage before
      injecting bone cement into a peri-articular cyst. This unusual complication
      highlights the need for rigorous evaluation of the benefits and risks of
      percutaneous injection of acrylic cement in the treatment of benign lesions,
      especially close to an articulation.

PMID- 10883448
TI  - Gross vertebral collapse associated with long-term disodium etidronate treatment
      for pelvic Paget's disease.
AB  - Inhibition of skeletal mineralisation is a well-recognized complication of
      disodium etidronate therapy that was identified in the earliest studies of its
      use in osteoporosis and Paget's disease. The effect is seen at lower doses in
      Paget's disease than in osteoporosis. Several cases of spontaneous fractures
      occurring in unaffected bones of Paget's patients have been reported. However, we
      believe the case described here is the most severe example of etidronate-induced
      osteomalacia published in the literature, featuring widespread vertebral collapse
      occurring as a consequence of nearly 10 years of uninterrupted etidronate
      treatment for isolated hemipelvic Paget's disease.

PMID- 10883449
TI  - Primary pulmonary osteogenic sarcoma.
AB  - A 56-year-old man initially presented to his family physician with tingling in
      the fingertips of his left hand. A chest radiograph revealed a left upper lobe
      mass. Local resection found a soft tissue osteogenic sarcoma. This is a report of
      a rare case of primary pulmonary osteogenic sarcoma.

PMID- 10883450
TI  - Metastatic bone tumor mimicking spontaneous osteonecrosis of the medial condyle
      of the femur: misleading appearance on MR imaging.
AB  - We report a case of a metastatic bone tumor that mimicked spontaneous
      osteonecrosis of the medial condyle of the femur on magnetic resonance imaging.

PMID- 10883451
TI  - D-2-hydroxyglutaric aciduria in association with spondyloenchondromatosis.
AB  - D-2-hydroxyglutaric aciduria is a rare metabolic disorder, first reported in
      1980, and does not yet have a clinically specific presentation pattern nor any
      specific treatment regime. We report a girl born with this uncommon metabolic
      disorder, who, at the age of 12 months, was also found to have a severe crippling
      form of skeletal dysplasia, spondyloenchondromatosis.

PMID- 10883452
TI  - Angiomyolipoma arising in the thigh.
AB  - A 41-year-old man presented with an asymptomatic mass in the right medial thigh.
      Magnetic resonance imaging (MRI) revealed a well-demarcated, 10-cm mass in the
      right adductor muscles. The margins of the mass exhibited high signal intensity
      and the rest showed low or iso signal intensity on T1-weighted MR images.
      However, the high signal intensity was decreased on T2-weighted images with fat
      suppression. The central part of the tumor was of inhomogeneous high signal
      intensity on T2-weighted images; after Gd-DTPA injection it enhanced in
      homogeneously on T1-weighted images with fat suppression. On dynamic computed
      tomography (CT) in the arterial phase, there were strongly enhancing spotty areas
      in the tumor. At surgery, a yellow-whitish tumor was resected and a pathological
      diagnosis of angiomyolipoma (AML) in the thigh was made.

PMID- 10883454
TI  - Primary clear cell sarcoma of bone.

PMID- 10883453
TI  - Chronic ulceration of the leg following extensive scarring due to a snake bite
      complicated by squamous cell carcinoma.
AB  - Chronic ulcers of the leg are common in Brazil, perhaps more common than in the
      developed world. We report a case of a chronic ulcer of the leg following
      extensive scarring due to a bite by a venomous snake, which eventually led to a
      squamous cell carcinoma.

PMID- 10883455
TI  - Extraskeletal myxoid chondrosarcoma of the knee.

PMID- 10883456
TI  - Clinicopathological study of brain metastasis in gastric cancer patients.
AB  - Brain metastasis from cancers of the gastrointestinal tract is uncommon; brain
      metastasis from gastric cancer is rare and its incidence is low. Brain metastasis
      of gastric cancer is often difficult to treat and is resectable in only a few
      cases. We have treated three patients who had a solitary brain metastasis after a
      gastrectomy. These three cases are reviewed along with eight other previously
      reported cases of brain metastasis to clarify the clinicopathological features
      and to suggest guidelines for patients with metastatic brain tumors. The
      clinicopathological features of 11 cases of brain metastasis were analyzed. For
      comparison purposes, the 11 cases were classified into three groups as follows: a
      resection group, a chemoradiotherapy group, and a nontreatment group. All the
      patients had advanced gastric cancer of stage III or more. The resection group
      had the most survivors, and survival rates decreased in the order of the
      resection group, the chemoradiotherapy group, and the nontreatment group. There
      was a statistically significant difference between the resection group and the
      nontreatment group (P = 0.0177). Aggressive multidisciplinary treatment,
      including a resection, for brain metastasis should improve the quality of life
      and prolong life expectancy.

PMID- 10883457
TI  - The usefulness, indications, and complications of laparoscopy-assisted colectomy
      in comparison with those of open colectomy for colorectal carcinoma.
AB  - The technique of laparoscopy-assisted colectomy (LAC) was developed for benign
      and malignant diseases of the colon and rectum; however, its feasibility and the
      associated clinical outcome remain unclear. We reviewed 45 patients who underwent
      LAC (LAC group) and 62 patients who underwent traditional open surgery (Open
      group) for colorectal carcinoma in our hospital, and compared the clinical data
      between the two groups in an effort to determine whether LAC is really minimally
      invasive and if it enhances the quality of life. So that the backgrounds of the
      patients in both groups were almost the same, we only compared data of patients
      with colorectal carcinoma of stages 0, I, and II. The duration of surgery in the
      Open group was significantly shorter for all procedures except sigmoid resection,
      but the blood loss was not significantly different between any of the procedures
      except for right colectomy. The time to the first passing of flatus and
      restarting oral intake, length of hospital stay, and duration of epidural
      analgesia were significantly shorter in the LAC group. The morbidity and
      mortality rates in the LAC group were almost the same as those in the Open group
      at 29.5% and 3.3% versus 22.6% and 1.6%, respectively. However, five major
      complications of LAC for advanced colorectal carcinomas might be prevented by
      performing an open procedure. In conclusion, LAC is a safe and minimally invasive
      surgical technique following which we can expect a faster recovery; however,
      patients with advanced colorectal carcinomas must be carefully selected for this
      operation.

PMID- 10883458
TI  - Recurrent incompetence of repaired floppy mitral valves and the severity of
      myxomatous degeneration.
AB  - The purpose of this study was to clarify whether or not severe myxomatous
      degeneration impairs the stability of a repaired mitral valve after valve
      conservative surgery. A total of 21 patients who underwent successful valve
      conservative surgery for pure isolated mitral incompetence were classified into
      two groups, one comprising those with stable mitral valve function and the other
      comprising those who developed recurrent incompetence within 1 year after
      surgery. The histological severity of myxomatous degeneration of the mitral
      leaflet was compared between the two groups, based upon microscopic observation
      and quantification of the myxomatous area in the fragment that had been
      surgically excised from the floppy mitral leaflet during valve-conservative
      surgery. The degree of myxomatous degeneration of the surgically excised fragment
      was significantly higher in the "recurrent" group than in the "stable" group (P =
      0.02). As a microscopically confirmed severely degenerative myxomatous mitral
      valve may develop recurrent incompetence after valve-conservative surgery within
      a relatively short period, careful and regular follow-up is required.

PMID- 10883459
TI  - Is median sternotomy invasive? A comparison between minimally invasive direct
      coronary artery bypass and off-pump bypass.
AB  - Although minimally invasive direct coronary artery bypass (MIDCAB) eliminates the
      need for median sternotomy and cardiopulmonary bypass, its indications are
      limited. Conversely, coronary artery bypass without cardiopulmonary bypass (off
      pump bypass) enables complete surgical revascularization under an optimal
      surgical field established by median sternotomy, even if patients have
      multivessel disease. The present study was designed to determine the invasiveness
      of median sternotomy by comparing 11 patients who underwent MIDCAB and 5 who
      underwent off-pump bypass between May 1997 and April 1998. There were no
      significant differences between the MIDCAB group and the off-pump group in age,
      being 57 +/- 11 vs 66 +/- 8 years old, the operative time, being 321 +/- 149 vs
      441 +/- 205 min, the number of grafts, being 1.0 vs 1.4/patient, peak creatine
      kinase (CK) values, being 662 +/- 436 vs 609 +/- 56 IU/l, the peak CK-muscle
      brain values, being 12 +/- 9 vs 16 +/- 5 IU/l, and the postoperative blood loss,
      being 369 +/- 198 vs 541 +/- 204 ml. Although there was no significant difference
      in peak C-reactive protein, at 17 +/- 5 vs 20 +/- 2 mg/dl, the periods declining
      within the normal ranges were shorter in the MIDCAB group than in the off-pump
      group, at 7 +/- 1 vs 15 +/- 2 days (P > 0.01). The hospital stay was almost the
      same in both groups, at 16 +/- 8 vs 26 +/- 14 days. These findings suggest that
      off-pump bypass is more invasive than MIDCAB, which may be attributed to the
      median sternotomy.

PMID- 10883460
TI  - Surgical treatment for chronic pleural empyema.
AB  - Various surgical procedures have been developed in an attempt to alleviate the
      significant problems caused by chronic pleural empyema. The present study
      evaluates our 11-year experience of employing a number of therapeutic approaches
      for chronic empyema. Between 1987 and 1997, 45 consecutive patients underwent
      treatment for chronic empyema at our hospitals. They comprised 21 patients (47%)
      presenting with post-tuberculosis, 11 (24%) receiving cancer therapy including
      pulmonary resection, and 13 (29%) with postpneumonic empyema. Omentopexy, lung
      resection, and thoracoscopic surgery were performed in 10 (22%), 5 (11%), and 4
      (9%) patients, respectively. Poor results of treatment were observed in two of
      the patients with post-tuberculous empyema, and three of the patients treated for
      cancer died of recurrence. The other 40 patients remain symptom-free. An
      improvement in quality of postoperative life was revealed by the exercise test
      rather than by static spirometry. Optimal therapy for chronic empyema requires
      selection of the most appropriate first and staged procedures for each patient.
      Moreover, lung resection should be minimal. In a critical state, open
      thoracostomy must be performed as the first procedure, while omentopexy or
      thoracoplasty should be restricted to selected cases. Dead space and minor air
      leakage may safely be left behind. A video-assisted procedure can be selected for
      postpneumonia empyema.

PMID- 10883461
TI  - Autologous blood donation with recombinant human erythropoietin for abdominal
      aortic aneurysm surgery.
AB  - We evaluated the efficacy of autologous blood donation using recombinant human
      erythropoietin for elective abdominal aortic aneurysm (AAA) surgery regarding
      postoperative recovery. Twenty-five AAA patients who completed surgery without
      receiving a homologous blood transfusion were divided into two groups, consisting
      of a control group (n = 12) who did not bank any autologous blood, and a donation
      group (n = 13) who did bank more than 800 ml of autologous blood with the use of
      erythropoietin. The hematocrit (Ht) level of the control group decreased from
      41.1% +/- 1.2% before the operation to 36.2% +/- 0.9% just afterwards (P > 0.01).
      In the donation group, however, the Ht did not change significantly during either
      the donation period or the perioperative period. The postoperative period before
      oral food intake and natural defecation were both significantly shorter in the
      donation group than in the control group. The first day of mobilization was also
      earlier in the donation group. In conclusion, autologous blood donation using
      erythropoietin for AAA surgery is therefore considered to promote the early
      recovery of patients.

PMID- 10883462
TI  - Identification of high-risk breast cancer patients from genetic changes of their
      tumors.
AB  - To identify the genetic prognostic markers for breast cancer, we analyzed loss of
      heterozygosity (LOH) at 11p, 16q, 17p, 17q, and 18q, as well as amplification of
      the ERBB2, INT2, and MYC genes, in 131 patients with breast carcinoma, 49 of whom
      had lymph node involvement, but none of whom had distant metastases. Among the
      several chromosome arms tested, LOH at 17q was correlated with lymph node
      metastasis. Amplification of the ERBB2, MYC, and INT2 genes was found more
      frequently in tumors from patients with lymph node metastases than in tumors from
      those without lymph node metastases. Univariate analysis demonstrated that LOH at
      17q and INT2 amplification were factors influencing disease-free survival (DFS).
      A multivariate analysis was performed on 89 tumors that were able to be evaluated
      for both LOH at 17q and INT2 amplification, and the results showed that patients
      who had tumors with these genetic changes were more likely to have a poor
      prognosis. The findings of this study suggest that investigating genetic changes,
      in addition to conventional clinicopathologic factors, may contribute to defining
      groups of breast cancer patients with differences in prognosis.

PMID- 10883463
TI  - Heparin reduces serum levels of endothelin-1 and hepatic ischemia reperfusion
      injury in rabbits.
AB  - Since the role of heparin in hepatic ischemia/reperfusion (I/R) injury is still
      not fully understood, we investigated the effects of heparin on hepatic I/R
      injury in rabbits. Heparin was injected into rabbits after inducing partial
      hepatic ischemia for 1 h. Thereafter, the serum levels of endothelin-1 (ET-1) and
      liver transaminase, and tissue levels of oxidized and deoxidized hemoglobin
      (oxHb, deoxHb) in the reperfused liver were analyzed. Microscopic examinations
      were also performed. The increased serum levels of ET-1 and liver transaminase
      after reperfusion were significantly reduced by heparin (P > 0.01). Hepatic
      ischemia reduced oxHb and increased deoxHb. Reperfusion with heparin immediately
      reduced deoxHb and increased oxHb, and thereafter the balance between the two
      kinds of Hb also recovered. However, reperfusion without heparin did not
      demonstrate any similar recovery, but instead gradually exacerbated the
      dissociation. Microscopically, heparin appeared to normalize I/R-induced
      activation of hepatic stellate cells which are the target cells for ET-1. These
      results suggest that heparin improves the hepatic I/R injury caused by sinusoidal
      microscirculatory disturbances partly via an inhibition of the ET-1 increase.

PMID- 10883464
TI  - Benign esophageal schwannoma: report of a case.
AB  - We report herein the case of an otherwise asymptomatic 62-year-old woman who was
      found to have an incidental esophageal lesion during endoscopic follow-up of an
      unrelated disorder. An esophageal submucosal tumor was diagnosed, and the patient
      was subsequently monitored on a regular yearly basis. As the diameter of the
      tumor doubled over a 4-year period, the possibility of a malignant lesion could
      not be excluded, and she was admitted to our hospital for further investigations.
      Esophagography, endoscopy, endoscopic ultrasonography, and computed tomography
      confirmed a submucosal tumor, 35 mm in length, in the thoracic midesophagus. A
      leiomyoma or leiomyosarcoma was suspected based on the known incidence of such
      tumors, and tumor enucleation was performed. Gross inspection revealed a solid
      tumor arising from the wall of the esophagus. Histopathologic examination showed
      intertwined bundles of spindle cells with spiral-like proliferation, and
      immunohistochemical studies were positive for S-100 protein, whereby a diagnosis
      of esophageal schwannoma was established. The patient experienced no
      postoperative complications, and her clinical course to date has been
      satisfactory. To date, 2 years 8 months after surgery, she has shown no sign of
      tumor recurrence and remains in good health.

PMID- 10883465
TI  - Multiple inflammatory pseudotumors mimicking liver metastasis from colon cancer:
      report of a case.
AB  - A 54-year-old man underwent an operation for colon cancer histologically
      diagnosed as moderately differentiated adenocarcinoma with clinical staging of
      Dukes C. He was prescribed carmofur for adjuvant chemotherapy. A follow-up
      computed tomography scan done 6 months later revealed two new low-density areas
      in the liver. A diagnosis of metastatic adenocarcinoma from the previous colon
      cancer was presumed, based on the patient's history and radiological findings,
      and resection of the affected area of liver was performed. Histological
      examination of these tumors revealed that they were inflammatory pseudotumors
      (IPT). The patient had an excellent postoperative course and has shown no further
      signs of recurrence in the 3 years since his last operation. IPT of the liver is
      a rare disease, for which no methods of diagnosis and treatment have been
      established, since it is difficult to distinguish IPT from hepatocellular
      carcinoma or metastatic carcinoma. We describe this case with a review of the 101
      cases of IPT documented in the Japanese literature, in the hope that it will
      contribute to the diagnosis and treatment of this unusual disease entity.

PMID- 10883466
TI  - Foreign body reaction to a metal clip causing a benign bile duct stricture 16
      years after open cholecystectomy: report of a case.
AB  - We present herein a case where a benign bile duct stricture developed 16 years
      after an open cholecystectomy and without any prior symptoms. The patient was
      thought to have a Klatskin tumor both pre- and intraoperatively and was treated
      with a resection of the mass and bile duct confluence, while
      hepaticojejunostomies were also performed to both ducts separately. A pathologic
      examination of the specimen revealed extensive fibrosis, chronic inflammation,
      and a nonnecrotizing granulomata. Any hilar mass presenting after upper abdominal
      surgery should therefore be considered to be potentially a benign bile duct
      stricture, even with a long symptom-free interval.

PMID- 10883467
TI  - Combining the selective arterial calcium injection test and intraoperative blood
      glucose monitoring for multiple insulinomas: report of two cases.
AB  - To date, no precise methods of preoperatively localizing multiple insulinomas or
      intraoperatively confirming their complete removal have been established. We
      describe herein the effectiveness of combining the selective arterial calcium
      injection (SACI) test to locate tumors preoperatively, with intraoperative
      continuous blood glucose monitoring (IOBGM) to confirm their complete removal.
      During the 8-year period from 1990 to 1997, we experienced two patients with
      multiple insulinomas. The first patient required resection of a residual tumor in
      the remnant pancreas for persistent hyperinsulinemia after a distal
      pancreatectomy performed under conventional diagnostic procedures. In the second
      patient, a SACI test was performed in addition to other diagnostic imaging
      procedures, and while computed tomography scan, endoscopic ultrasonography, and
      arteriography demonstrated multiple tumors in the body and tail of pancreas, the
      SACI test suggested that there were also tumors in the head of pancreas.
      Intraoperative ultrasonography showed a tumor measuring 5 mm in diameter on the
      surface of the head of the pancreas, apart from the multiple tumors in the body
      and tail of the pancreas. Complete removal of all tumors was assessed by the
      hyperglycemic rebound after resection of the tumors, determined by IOBGM. Based
      upon our experience, we believe that the SACI test and IOBGM are helpful for
      establishing precise localization and achieving complete removal of multiple
      insulinomas.

PMID- 10883469
TI  - Herniation through both Winslow's foramen and a lesser omental defect: report of
      a case.
AB  - The herniation of small bowel through Winslow's foramen is a rare type of
      internal hernia which can cause ileus; however, a hernia traversing the lesser
      sac is even more unusual. To the best of our knowledge, only 25 cases of
      herniation through Winslow's foramen and 10 cases of lesser sac hernia have been
      reported in the Japanese literature. We describe herein the case of a 33-year-old
      man who presented to our hospital complaining of abdominal pain in whom a plain
      abdominal radiograph revealed small bowel gas with air-fluid levels, suggesting
      ileus. Following admission, an ileus tube was inserted, but the intestinal shadow
      did not improve and surgery was performed based on suspicion of an internal
      hernia. Approximately 100 cm of ileum was found to have herniated through a
      defect in the lesser omentum after passing through Winslow's foramen. Since the
      herniated bowel was viable, manual reduction without resection was performed. The
      patient had a satisfactory postoperative course, and was discharged on
      postoperative day 11. There are many unknown aspects surrounding the etiology of
      Winslow's foramen hernia and lesser sac hernia, and although internal hernia is a
      rare cause of ileus, its possibility should be kept in mind.

PMID- 10883468
TI  - The effectiveness of administering a minimal dose of octreotide long-term prior
      to surgery for insulinoma: report of a case.
AB  - We report herein the case of an 80-year-old woman with insulinoma who was
      regarded as an unsuitable candidate for immediate surgery due to her advanced age
      and obesity, for whom octreotide, a long-acting analogue of somatostatin, was
      used to improve her hypoglycemia and hyperinsulinemia without hyperalimentation.
      Administering a minimal dose of octreotide for a long period resulted in the
      improvement of leg edema, weight control, and cardiopulmonary function, and
      resection of the pancreatic tumor was safely carried out without any
      complications.

PMID- 10883470
TI  - The occurrence of a strangulated ileus due to a traumatic transmesenteric hernia:
      report of a case.
AB  - We report herein the case of a 6-year-old boy in whom a strangulated ileus was
      caused by a traumatic transmesenteric hernia. The boy had fallen from his bicycle
      and suffered a severe blow to the abdomen. Abdominal pain and vomiting developed
      10 h after the accident and he was admitted to our hospital. Abdominal
      ultrasonogram and computed tomogram demonstrated ascites, intestinal wall
      thickening with fluid, and an engorged radiating mesenteric vasculature. Thus, an
      emergency laparotomy was performed which revealed bloody ascites, a strangulated
      ileus, and torsion with a transmesenteric hernia. The necrotic intestine was
      resected and an anastomosis was performed. Macroscopic and microscopic findings
      revealed a traumatic mesenteric rent. The unusual presentation of this case is
      discussed.

PMID- 10883471
TI  - Invagination induced by a long intestinal tube: report of a case.
AB  - Invagination induced by a long intestinal tube is rarely encountered. We report
      herein one such case of a 62-year-old man who was successfully treated by
      laparoscopically reducing the invagination, then performing partial resection of
      the small intestine.

PMID- 10883472
TI  - Successful implantation of a bipolar epicardial lead and an autocapture pacemaker
      in a low-body-weight infant with congenital atrioventricular block: report of a
      case.
AB  - A permanent pacemaker system was successfully implanted into a low-body-weight
      infant with congenital atrioventricular (AV) block, using a bipolar epicardial
      CapSure Epi lead and an autocaptured Pacesetter Solus-micro VVIR pacemaker. The
      calculated life span of the pacemaker generator is 5 years with a heart rate of
      120/min and an output of 1.2 V (0.31 ms), and fortunately, its threshold was
      autocaptured. Thus, we can conclude that the combination of a steroid-eluted
      bipolar epicardial lead and the smallest possible autocaptured pacemaker
      generator is most suitable for a neonate or young infant.

PMID- 10883473
TI  - Tension hemothorax caused by a ruptured aneurysm of the descending thoracic
      aorta: report of a a case.
AB  - The rupture of an aneurysm of the descending thoracic aorta into the right
      thoracic cavity is a comparatively rare event, and it is very difficult to
      establish a diagnosis immediately and rescue such patients. We describe herein
      the successful surgical treatment of a patient with this life-threatening
      emergency by initiating immediate cardiopulmonary bypass. It is mandatory to
      drain the right thoracic bleeding through a left thoracotomy without delay to
      release the tension hemothorax. Furthermore, it is necessary to evacuate the
      right thoracic hematoma through a right thoracotomy because complete removal o f
      a hugh hematoma through a left thoracotomy cannot be effectively achieved.

PMID- 10883474
TI  - Long-term survival of a patient with stage IV pulmonary large cell carcinoma
      achieved by combined-modality therapy: report of a case.
AB  - We describe herein the case of a 59-year-old-man with stage IV pulmonary large
      cell carcinoma and a giant brain metastasis, in whom two sublines with different
      growth characteristics and drug sensitivities in vitro were established from the
      primary tumor. Disease-free survival for more than 5 years after surgery was
      achieved by combined-modality therapy together with surgery to remove the primary
      tumor, radiation to the brain metastasis, and chemotherapy to presumed
      hematogenous dissemination. Subline 1 proliferated in a monolayer of epithelial
      like cells, while subline 2 showed a floating colony pattern of proliferation,
      resembling the typical growth characteristics of small cell lung cancer (SCLC)
      cells in vitro. Subline 2 was sensitive to a number of drugs, namely, vincristine
      (VCR), cyclophosphamide (CPM), adriamycin (ADR), and cisplatin (CDDP), whereas
      subline 1 was resistant to many drugs. The patient was treated with a combination
      of 44 Gy of whole-brain irradiation and a number of cycles of chemotherapy
      comprised of ADR, VCR, and CPM, followed by CDDP, VCR, and CPM, based on the
      results of sensitivity testing of the subline 2 cells. As a result, the patient
      has been disease-free for more than 5 years postoperatively. In conclusion, this
      case report serves to demonstrate that meticulous combined-modality treatment
      taking tumor heterogeneity in human cancers into account may be necessary to
      achieve breakthroughs in current cancer therapy for advanced lung cancer.

PMID- 10883475
TI  - Successful reconstruction in a patient with chronic and multisegmental venous
      obstruction: report of a case.
AB  - We describe herein our technique of performing complex venous reconstruction for
      a patient with chronic, multiple, and long segmental venous obstruction from the
      left iliac vein to the infrapopliteal deep veins. To improve venous outflow and
      prevent venous gangrene caused by graft failure, we preserved the ipsilateral
      saphenous vein without dissection and performed complex venous reconstruction in
      the form of iliofemoral crossover bypass using a prosthetic graft,
      femoropopliteal bypass using the contralateral saphenous vein, both
      thromboembolectomy and venous repair of the infrapopliteal veins, and the
      creation of a distal arteriovenous fistula. The successful outcome of this
      surgery may provide some insight into the treatment of extended chronic venous
      obstruction.

PMID- 10883476
TI  - A simple technique of using novel thread-holding and knot-pushing forceps for
      extracorporeal knot-tying.
AB  - We designed some novel knot-pushing forceps for extracorporeal knot-tying and
      describe herein our simple technique of utilizing them. These forceps are
      modified only by a single 1-mm hole between their jaws, which hold a thread and
      push the knot toward the ligating tissue. The application of this simple device
      was handled well by surgeons beginning to perform advanced endoscopic surgery.
      The simple modification explained in this report seems applicable to most of the
      forceps currently used.

PMID- 10883477
TI  - [I Guidelines of the Brazilian Cardiology Society for Heart Transplantation: II.
      Heart transplantation in children].

PMID- 10883478
TI  - [I Guidelines of the Brazilian Cardiology Society for Heart Transplantation: III.
      Patient selection].

PMID- 10883479
TI  - [I Guidelines of the Brazilian Cardiology Society for Heart Transplantation: IV.
      Rejection].

PMID- 10883480
TI  - [I Guidelines of the Brazilian Cardiology Society for Heart Transplantation: V.
      Complication after heart transplantation].

PMID- 10883482
TI  - [I Guidelines of the Brazilian Cardiology Society for Heart Transplantation: VII.
      Technical aspects of heart transplantation].

PMID- 10883483
TI  - [I Guidelines of the Brazilian Cardiology Society for Heart Transplantation:
      VIII. Orientation and criteria to donor selection].

PMID- 10883481
TI  - [I Guidelines of the Brazilian Cardiology Society for Heart Transplantation: VI.
      Alternatives or bridge to heart transplantation].

PMID- 10883484
TI  - [I Guidelines of the Brazilian Cardiology Society for Heart Transplantation: IX.
      Organization of heart transplantation in Brazil].

PMID- 10883485
TI  - [Body height and Graffar's socioeconomic score variables relationship in males
      aged 7 to 13 years].
AB  - The following study is of an exploratory and operational nature. Its main
      objective consists of the estimation of a lineal correlation coefficient between
      two of the most important variables that have been studied in the Proyecto
      Venezuela of Fundacredesa; Height, and Graffar Socioeconomical Score of Mendez
      Castellano. The reached value (r = -0.28) which is based on choice
      considerations, restrictions, and the adjustment to a pertinent universe,
      constitute the maximum value that could have been achieved as of the sample
      gathered in the Proyecto Venezuela. To be able to calculate such value, it was
      necessary to implement heuristic procedures, designing and producing a complex
      model of statistical processing. This model allows the estimation of the
      correlation coefficient as if this coefficient was already obtained from
      individual and raw data level, but, in this case starting from the Proyecto
      Venezuela's published information, that only shows aggregate average values.
      While processing the data--additionally to the principal conclusion of the work
      that was obtaining the maximum value of the correlation coefficient--it was found
      that the average of the height variable, at each age group, remained basically
      unaltered in the I and II Social and Economical Strata, independently of the
      values that are reached in the Graffar Score.

PMID- 10883486
TI  - [CMACPAR an modified parallel neuro-controller for control processes].
AB  - CMACPAR is a Parallel Neurocontroller oriented to real time systems as for
      example Control Processes. Its characteristics are mainly a fast learning
      algorithm, a reduced number of calculations, great generalization capacity, local
      learning and intrinsic parallelism. This type of neurocontroller is used in real
      time applications required by refineries, hydroelectric centers, factories, etc.
      In this work we present the analysis and the parallel implementation of a
      modified scheme of the Cerebellar Model CMAC for the n-dimensional space
      projection using a mean granularity parallel neurocontroller. The proposed memory
      management allows for a significant memory reduction in training time and
      required memory size.

PMID- 10883487
TI  - [Lewis acids mediated synthesis of 4-aminoquinolines].
AB  - The synthesis of 4-amino-2-quinolines from N-phenylcyanoacetamides and of 4
      aminoquinolines from 2-aminobenzonitrile and beta-dicarbonylic compounds was
      accomplished using Lewis acids as catalysts.

PMID- 10883488
TI  - [High resolution ECG signals in Chagas patients: SEARCH project].
AB  - This work presents contributions to the study of a public health problem known as
      Chagasic Myocarditis. The results of the efforts done in Venezuela to understand
      the evolution of this disease through a novel technique called High Resolution
      Electrocardiography (HRECG) are discussed. A review of this methodology is
      presented and also its potential as a tool to study Chagas disease and to
      diagnose its different myocardial manifestations is discussed in detail. Several
      research approaches are presented as well as the results obtained, new techniques
      for HRECG interpretation such as the analysis of signals from the P-R segment,
      the intra QRS potentials, and late potentials. This method contributes to early
      detection and follow up of Chagas myocarditis. The collection and the
      organization of a HRECG data base that served as the basis for SEARCH, which is a
      valuable resource for new research lines is also described.

PMID- 10883489
TI  - The control of hydatidosis.

PMID- 10883490
TI  - [Seroprevalence of T. cruzi infection in 6- and 12- year-old school children from
      three Uruguayan endemic departments].
AB  - The last national survey on seroprevalence of T. cruzi human infection in
      Uruguay, showed a 3.4% in adults from endemic areas. Since 1983, antivectorial
      actions of the control program have been carried out continually. In consequence,
      household infestation by Triatoma infestan, the main vector of T. cruzi in
      Uruguay, decreased in all endemic areas and was completely eliminated in some of
      them. The objectives of the present work are to evaluate the new
      seroepidemiological situation. A representative sampling of rural and urban
      population was undertaken, to include six and twelve year-old school children
      from three departments: Artigas, Rivera and Tacuarembo. The whole sample included
      4,722 school children, evaluated by the indirect immunofluorescence (IFI) test
      for Chagas disease. The seroprevalence of T. cruzi infection in the six year-old
      group was 0.3% in Artigas, 0.6% in Rivera and 1.0% in Tacuarembo. The
      seropositive children with seropositive mothers support the possible congenital
      transmission.

PMID- 10883491
TI  - [Immune humoral response in pigs infected with eggs and posoncospheres of Taenia
      solium].
AB  - Due to the importance of cysticercosis in Mexico and Latin America and to the
      fact that in the last years another mechanism of infection for this disease has
      been proposed, i.e. through postoncospheres and immunosuppression of the host, we
      have considered relevant to perform the present work, which consisted in
      assessing the immune response induced by dexamethasone as well as that produced
      by parasites in pigs infected with T. solium eggs, or postoncosphere-infected,
      and in postoncosphere-infected and dexamethasone-treated animals. We used 10
      recently weaned pigs, three were used as controls, two of them without the drug
      and one with it; two were infected with T. solium eggs; five with postoncospheres
      receiving also dexamethasone three of them. We evaluated the humoral response
      against parasite antigen using indirect haemagglutination (IH) and ELISA methods.
      Results of the immune humoral response revealed titres of up to 1:128 in T.
      solium eggs infected animals, of 1:16 in postoncosphere infected animals, and of
      1:32 towards the end of the experiment in postoncosphere plus dexamethasone
      animals. Absorbance titres with ELISA confirmed these findings. Data obtained by
      IH show that the antibody titres of the pigs challenged with postoncospheres and
      postoncospheres plus dexamethasone are positive as compared to the titres
      obtained in the pigs infected with T. solium eggs. Results from the ELISA
      confirmed this finding, since, from weeks 14 to 17, the pigs became positive,
      behaving as those pigs that developed cysticercosis. This is relevant as it
      indicates that the antiposcosphere antibodies recognized antigens of T. solium
      larvae.

PMID- 10883492
TI  - [Treatment of hepatic hydatid cysts by percutaneous aspiration and hypertonic
      saline injection: results of a cooperative work].
AB  - Percutaneous puncture-aspiration-injection-reaspiration (PAIR) of hydatid liver
      cysts, was performed in 38 patients 14-80 years old, with a total of 60 liver
      hydatid cysts. After aspiration under computed tomography guidance, hypertonic
      saline was injected into the cystic cavities of patients as a scolecidal agent.
      No major complications were associated with the procedures. In the follow-up
      period of 18 months, control CT scans of 35 cysts revealed a gradual decrease in
      cyst size with a mean volume reduction of 66%. Complications included two cases
      of urticaria, one case of anaphylaxis and one subcapsular hematoma. No mortality
      occurred. It is concluded that percutaneous aspiration and hypertonic saline
      injection for liver hydatid cysts appears to be an effective form of treatment
      and may eventually prove to be an alternative to surgical intervention.

PMID- 10883493
TI  - [Human hydatidosis in Chile. Seroprevalence and estimate of the number of
      infected people].
AB  - Chile is located in the southwestern border of South America. The country is
      4,329 km long and 96-342 wide. From north to south it is divided into five marked
      different biogeographical zones: deserts, steppes, bushes, forests (cattle
      raising) and austral (sheep raising). Population (June 1999) 15,017,760 (14.6%
      rural). Human hydatidosis is endemic in Chile. According to Ministry of Health
      information about 320 cases are registered each year. In order to find out the
      likely prevalence of human hydatidosis in Chile, a series of serosurveys was
      carried out in 1988-1997 throughout the total country. By using the indirect
      hemagglutination reaction and ELISA for hydatidosis (tests with good sensibility
      and specificity) 60,790 unselected apparently healthy persons: 41,399 from urban
      areas (16,428 blood donors, 13,894 delivering mothers and 11,077 middle grade
      schoolchildren) and 19,361 from rural areas--from randomly selected family
      groupings--were studied. A total individuals 82 (136/100,000) resulted positive:
      36 (87/100,000) urban and 46 (241/100,000) rural, being the prevalence higher in
      rural areas, particularly in the southern austral zone (mean 1068/100,00). These
      figures agree with those observed in clinical epidemiological studies. In
      conformity with the present results, in the whole country 17,002 individuals
      should have hydatidosis: 10,318 urban and 6,784 rural. All these possible
      infected people, not necessarily should present pathology in the future, as it
      has been observed in autopsies from unselected individuals, performed at the
      Medico-Legal Service in Santiago, in whom 71.3% of diagnosed hydatosis with
      hydatid cysts in many different locations, was an autopsy finding.

PMID- 10883494
TI  - [Ecological aspects between Contracaecum sp. (Nematoda, Anisakidae) and the host
      Serrasalmus spilopleura Kner, 1860 (Pisces, Characidae) in natural populations of
      northeastern Argentina].
AB  - From February 1987 to February 1989, the populational biology of Contraceacum sp.
      (larvae) in its paratenic host, the fish Serrasalmus spilopleura Kner, 1860, was
      studied in two ponds in a subtropical permanent habitat northeastern of
      Argentina. Fishes from Ramada Paso pond presented 80% of prevalence and 1 to 132
      larvae per fish while fishes from Aeroclub pond presented 63% of prevalence and 1
      to 184 larvae per fish. Fishes collected from Aeroclub pond have shown a high
      prevalence of infection during the first period of study (1987), diminishing the
      following year. In fishes from Ramada Paso pond the prevalence varied not
      significatively during the two years. Prevalence and mean intensity of infection
      increase with body length and weight of the hosts. Sex of hosts is not an
      influential factor in parasitic level. The lenitic "closed" environmental (Ramada
      Paso pond) evidenced the greatest larvae mean intensity and prevalence. Although,
      the lenitic "open" environmental (Aeroclub pond) showed the greatest parasitic
      number of individuals in an infrapopulation. The spatial dispersion in both ponds
      were aggregated and fit well a negative binomial model. Nevertheless, the
      Aeroclub pond presented the greatest overdispersion.

PMID- 10883495
TI  - [Housedust mites in Punta Arenas city, Chile].
AB  - In medicine, the importance of mites in house dust gains importance from day to
      day. The close relation between these arthropods and man is the cause of a series
      of health problems such as allergic asthma, rhinitis and/or dermatitis. House
      dust samples were collected between January and December 1991 in Punta Arenas,
      city, Chile. Samples were processed by the Artigas and Casanueva (1983)
      technique, modified by Munoz et al. (1983). The isolated specimens were
      subsequently identified using the Artigas and Casnueva (1983) pictorial key. Of
      the 134 samples study, 29.1% presented one or more mite species. A total of 13
      species were classified. Eight of them were registered for the city of Punta
      Arenas for the first time. Average weight of the dust analysed was 8.4 g. Mites
      were found from 0.2 g. onwards. A total of 1768 specimens was collected. The
      species more representative were: Blomia tjibodas (30.1%), Glycyphagus destructor
      (22.5%) and Tyrophagus putrescentiae (10.8%). The seasons that presented the
      higher proportions of mites were autumn (39.4%) and spring (37.1%).

PMID- 10883496
TI  - [Risk markers in subjects with high loads of Ascaris lumbricoides in a rural
      community of the Cojedes State , Venezuela].
AB  - A total of 337 individuals from a rural community of Venezuela (Mapurite, Estado
      Cojedes) was studied. Stoll faecal examination was carried out and the total
      number of A. lumbricoides was recovered after the treatment of the individuals
      sampled with Pyrantel pamoate at a dose of 10 mg/kg body weight in children and
      15 mg/kg in adults. A relationship between the high worm burden condition
      (individuals excreting more than 10,000 epg of A. lumbricoides) and the age of
      the hosts was found. Resulting with the major values of relative risk index (Rr)
      the 5-9 years old class (Rr = 3.2 t = 3.4). This relationship was not found
      between high worm burden condition (HWB) and the sex of the hosts. The following
      individuals have the the highest possibilities to become HWB: with blood group A
      (Rr = 3.05 t = 4.08), with haemoglobin type HbA HbS (Rr = 1.86 t = 2.13),
      individuals with the combinations A HbA HbF (Rr = 3.46 t = 2.31) and A HbA HbS
      (Rr = 3.11 t = 2.78). It was estimated that the selective treatment of the total
      HWB detected (72) with an effective product, determined a reduction of 95.4% of
      the environmental contamination with de eggs and 72.3% of the worm burden.

PMID- 10883497
TI  - [Massive trichuriasis in an adult diagnosed by colonoscopy].
AB  - A case of massive trichuriasis in a 37-year-old female from a rural locality of
      the Metropolitan Region of Chile, with antecedents of alcoholism, chronic hepatic
      damage and portal cavernomatosis, is presented. Since 12 year ago she has had
      geophagia. In the last six months she has frequently presented liquid diarrhea,
      colic abdominal pains, tenesmus and sensation of abdominal distention. Clinical
      and laboratory tests confirmed her hepatic affection associated with a celiac
      disease with anemia and hypereosinophilia. Within a week diarrhea became worse
      and dysentery appeared. A colonoscopy revealed an impressive and massive
      trichuriasis. The patient was successfully treated with two cures of 200 mg
      tablets of mebendazole twice daily for three days with a week interval. After the
      first cure she evacuated a big amount of Tricuris trichiura, fecal evacuations
      became normal, geophagia disappeared and recovered 4 kg of body weight.

PMID- 10883498
TI  - [Human ectoparasitoses: current status in Uruguay].
AB  - The present status of human ectoparasitoses in Uruguay is analyzed with the main
      purpose of performing in the future, comparative studies in the region. After
      classifying ectoparasites in temporary and permanent, comments are made on
      particular clinical and epidemiological aspects of some of them. For remarking:
      the high prevalence of pediculosis capitis and scabies; the frequent observation
      of cutaneous myiasis by Dermatobia hominis with a very interesting modification
      of the geographical national distribution of the fly and the presence of an
      endemic area of creeping eruption by Ancylostoma braziliense and A. caninum in
      the north of the country.

PMID- 10883499
TI  - [Standardization of ELISA IgM and IgA for immunodiagnosis of human trichinosis].
AB  - An ELISA test for trichinosis using as antigen a larvae soluble fraction from
      Trichinella spiralis was carried out for the detection of IgM and IgA specific
      antibodies in 45 serum samples from patients confirmed or suspected to have
      trichinosis by strong clinical and epidemiological evidences. All the patients
      had positive serology detected by precipitin test, bentonite floculation test,
      indirect hemagglutination test and ELISA IgG test. The cut-off value was
      determined using two criteria. Criterion A was determined in each plate, using
      three positive controls and two negative ones; the average of the negative
      controls and the weakest positive control, multiplied by a 1.2 factor was,
      considered the cut-off value. Criterion B was determined using the average plus
      three standard deviations from 64 apparently healthy persons serum samples. In
      both cases, three serum dilutions (1:10, 1:100 and 1:500) were used. The
      sensitivity of ELISA IgM was 100.0, 93.3 and 82.2% using serum dilutions of 1:10,
      1:100 and 1:500 respectively (criterion A) and 100.0, 97.8 and 95.6% for the same
      dilutions (criterion B), whereas the values for ELISA IgA were: 100.0, 91.1 and
      86.7% (criterion A) and 100.0, 100.0 and 91.1% (criterion B). In order to find
      out the specificity of ELISA IgM and ELISA IgA, additional 118 serum samples from
      individuals with other parasitoses, such as cysticercosis (18) hydatidosis (39),
      fascioliasis (12), toxocariasis (30), Chagas' disease (12) and individuals with
      non-specific eosinophilia (7), were also tested. ELISA IgM presented a
      specificity of 92.3, 93.4 and 97.3% (criterion A) and 96.2, 97.8 and 97.8%
      (criterion B) whereas the results for ELISA IgA were 97.8, 98.9 and 99.4%
      (criterion A) and 98.4% for the 1:10 and 1:100 dilutions and 100.0% for the 1:500
      dilution (criterion B). The positive predictive values of ELISA IgM were 76.3,
      77.8 and 88.1% (criterion A) and 86.5, 91.7 and 91.5% (criterion B) whereas the
      negative ones were 100.0, 98.3 and 95.7% (criterion A) and 100.0, 99.4 and 98.9%
      (criterion B). The positive predictive values of ELISA IgA were 91.8, 95.3 and
      97.5% (criterion A) and 93.8, 93.8 and 100.0% (criterion B) whereas the negatives
      ones were: 100.0, 97.8 and 96.8% (criterion A) and 100.0, 100.0 and 97.8%
      (criterion B). The use of ELISA IgM and ELISA IgA in the immunodiagnosis of
      trichinosis is discussed.

PMID- 10883500
TI  - Hydatidosis in the province of La Pampa, Argentina, 1998.
AB  - Echinococcus granulosus is the agent that causes the classical hydatidosis or
      cystic echinococcosis. The most spread cycle in South America is the sheep-dog
      cycle, and offers favorable conditions for the development of the parasite. As
      the province of La Pampa shows an endemic presence with notification of cases and
      infected dogs, the present work has the aim of contributing to the study of the
      distribution and prevalence of the disease in the district of Maraco, La Pampa,
      Argentina. Dogs of 36 farms that had ovines, were dosed with arecoline
      hydrobromide at a dose of 3.5 mg/kg. Dogs from 27 (75%) farms resulted positive
      to Tenia sp. and 3 (8.3%) to E. granulosus. Blood samples were taken to all the
      people living in all the inquired farm and were processed by the ELISA test for
      hydatidosis. A retrospective survey on cases of human hydatidosis attended in the
      Hospital of General Pico, head if the sanitary region, and in two private clinics
      was performed. Analysis of clinical records indicated 11 cases operated during
      the period 1996/1997 (annual incidence rate of 6.8 per 100,000 inhabitants). It
      is of public health interest to fulfill epidemiologic investigations in other
      districts of the Province of La Pampa with the aim of delimitating the endemic
      distribution within the province and also organizing surveillance systems on
      human hydatidosis.

PMID- 10883501
TI  - [Epizootic outbreaks of trichinosis in 2 pig farms from the Metropolitan Region
      of Chile].
AB  - In Chile swine trichinosis has presented a progressive decreasing in the last two
      decades of XX century. T. spiralis pig infection descended from an average of
      0.683 per 1000 in 1980-1984 to 0.315 in 1985-1989 and to 0.115 in 1990-1996. In
      the particular case of Metropolitan Region this decreasing has been more marked:
      from an average of 0.058 per 1000 in 1990-1994 to 0.003 in 1995-1999. Between the
      end of June 1999 and middle January 2000 in Metropolitan Region abattoirs T.
      spiralis was detected in 15 (4.9%) out of 306 swine from two pigsties located in
      El Monte (E.M.) and Padre Hurtado (P.H.) 45 and 30 km south-west from Santiago.
      In the same period another four pigs from the same premises were found infected
      in abattoirs of other regions. During inspection visits it was stated that both
      pig farms had deficient sanitary conditions. Phototrichinoscopy was positive in
      three out of five Rattus norvegicus collected in E.M. In pigsty PH the
      examination of diaphragm samples of 25 dogs and 17 cats resulted negative. In the
      premises originating T. spirali infected swine the Metropolitan Environmental
      Health Service Abattoirs Program carries out an epidemiological vigilance
      consisting in the follow-up of animals destined for slaughtering in order to
      initiate prophylactic actions oriented to eliminate eventual sources of
      trichinosis infection for human and rearing pigs.

PMID- 10883502
TI  - Redescription of Procamallanus mathurai Pande, Bhatia and Rai, 1963
      (Camallanidae: Nematoda).
AB  - The present species, identified as Procamallanus mathurai obtained from the
      stomach and intestine of fresh water fish Heteropneuste fossilis (Bloch) is
      redescribed. Position of vulva preequatorial which was not described earlier by
      Pande et al., 1963 and it differs from the original description in the size of
      spicules.

PMID- 10883503
TI  - [Basic aspects of neuroendocrinoimmunology].
AB  - The purpose of this article is to discuss basic aspects of the interplay between
      the neuroendocrine and the immune systems. Two pathways link the brain and the
      immune system: the autonomic nervous system and the neuroendocrine outflow via
      the pituitary. Most of the influence of the brain on immune events is exerted
      through the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, certain
      neurotransmitters, neuropeptides, and neurohormones affect immune function both
      in vivo and in vitro. Receptors for these molecules are present on immune cells.
      This cell-to-cell communication is bi-directional, since impulses from the immune
      system can affect many functions of the central nervous system. Cytokines
      released during the activation of the immune system, in turn, can alter the
      function of the HPA axis. In this context, we also describe our main findings
      working with a model of Candida albicans infection in rats exposed to chronic
      varied stress.

PMID- 10883504
TI  - [Differential expression of mucin carbohydrates in human endometria].
AB  - The use of Lectins to identify oligosaccharides in mucin substances has been
      increased by the role played by cell surface carbohydrates in invasion and
      metastasis processes. We studied in this work normal endometrial tissue, with
      benign and malignant entities in search for the presence of the Galactose beta 1
      3 N Acetylgalactosamine(Gal beta 1-3 GalNAC alpha and Galactose beta 1-3 N
      Acetylgalactosamine (Gal beta 1-3 alpha and beta) using the Lectins: Agaricus
      bisporus (ABL) and Arachis hipogea (PNA) respectively. The specific control were
      baths with galactose for PNA and with porcine stomach mucin for ABL. The use of
      these two Lectins allowed to differentiate substances bonded or non bonded to
      Sialic Acid, since PNA fails to label when the oligosaccharide is bonded to this
      acid Sialic. Significant differences were noticed on the bonding patterns of both
      Lectins on tissues with benign, malignant and normal entities. In this latter
      case the labelling was always continuous in both Lectins whereas it was irregular
      in the carcinoma.

PMID- 10883505
TI  - [The esophagus in patients with Chagas disease in Cordoba, Argentina. Histologico
      immunohistochemical, and evacuation time].
AB  - With the purpose of to establish the status of the oesophagus with respect to
      chagasic aendemia in subjects of the central rural zone of Argentine, we search
      the esophagic evacuation duration-time by means of a radiologic standardized test
      which studied the ingested barium transit as well us the caliber of a given
      oesophagus. 87 chagasic subjects from rural zones of Cordoba and Santiago del
      Estero, Argentina, were studied. All had several positive serological test for
      Chagas' infection. As controls 120 similar studies performed in subjects with
      negative serological tests for Chagas were considered. Besides, an
      histopathologic study on samples of oesophagus of four cases of chagasic patients
      deceased by different causes, and selected at random were performed, regarding
      the plexus of Auerbach and the muscle layers. RESULTS: 63% of chagasic subjects
      showed lengthening of esophagic evacuation; 35% of these referred some symptoms
      of oesophagic disfunctionalism. However, most of the cases corresponded to Group
      I of the Rezende's classification, that is, with normal caliber of oesophagus
      with slow transit and retention of barium. Only 3 cases were of group II. The
      histopathologic study showed diminution of the size and the number of neural
      structures of the Auerbach plexus as well as of the number of the neurone cells;
      in all they there were moderate infiltration by T-lymphocytes. In some areas
      there were replacement of neural structures by fibrosis. CONCLUSIONS: The
      analysis of results by age groups, showed that abnormal peristalsis of the
      oesophagus was present since the early ages of chagasic subjects, and affected a
      growing number in adult and elderly groups. Great megaesophagus were infrequent
      in these chagasic, suggesting that in the production of Groups III and IV of
      chagasic megaesophagus, that are frequent in other regions of South America,
      could intervene other factors.

PMID- 10883506
TI  - [Tumors with rhabdomyoblasts and neuroblasts].
AB  - A metallic impregnation technique, Del Rio Hortega's double impregnation, to
      evidence neuroblasts and rhabdomyoblasts, with recommendations as to the times of
      impregnation to obtains better results is evaluated. The images obtained are
      highly demonstrative both of the embryo elements of the primitive mesenchyma from
      myoblast, myotube, a rhabdomyoblastic ribbon cell with transverse streaks to the
      neoplastic elements of this lineage and to the neuroblasts with their extensions.
      The study material includes a renal tumor of Wilms with rhabdomyoblasts and
      neuroblasts and a cerebellum neuroblastoma with a rhabdomyoblastic element. These
      injuries are considered dysembryoplasic. We also studied two botryoid embryo
      rhabdomyosarcomas, begin one or them unusually found in a menopausic woman, two
      Muller mixed tumors of the uterus and Fallopian tubes, a rhabdomyoma in pharynx
      and three human embryos from aborted material between 5 and 13 weeks old. We
      emphasize the use of double impregnation to study rhabdomyoblasts and
      neuroblasts. In rhabdomyosarcomas, structures and elements similar to those of
      the embryo stage--racketoid and ribbon cells, myotubes and rhabdomyoblasts--can
      be observed. The tumor of Wilms is a dysembryoplasic tumor composed of renal
      blastem where we have found rhabdomyoblasts and neuroblasts. In the cerebellum
      neuroblastoma we observe rhabdomyoblasts with certain organism (ectomesenchyma).
      Finally, we describe a rather infrequent case of a cervix botryoid
      rhabdomyosarcoma of a menopausic woman.

PMID- 10883507
TI  - [Diabetes mellitus mortality in the Province of Cordoba: during the 1986-1995
      period].
AB  - The fact that Diabetes Mellitus has become one of the relevant health problems
      and is besides an important death cause in the world, has led to investigate
      mortality as produced by this pathology in the Province of Cordoba during the
      period 1986/1995. Death register because of Diabetes Mellitus for the whole
      province(for years 1986-1995) were obtained from the Stadistic Department of the
      Health Ministry of the Province of Cordoba. Brute and specific rates based on sex
      and age groups were determined from a total of 6.718 deceased (3,300 males and
      3,418 females), evolution of the same and its relation with diverse variables
      such as instruction level, poor housing and U. B. N.(Unsatisfied Basic Needs).
      Result showed that death rate increased during the period Studied, 24.42/100,000
      being the medium annual rate, with no significative difference between both sexes
      (P = 0.76 > 0.05). In relation to age, rates raised according to growing age,
      with prevalence of the masculine, in general from 45 years and onward, except for
      1986, 1989 and 1995 years when feminine death rate is greater in the 75 years-old
      and onward group. With regard to the other variables considered, when comparing
      them with the social and economic development of each Department in the Province
      of Cordoba, we could infer that industrialization, urbanization and social and
      economic evolution of the same have a positive correlation with mortality caused
      by diabetes.

PMID- 10883508
TI  - [The importance of IgG auto-antibodies, anti-collagen type II specific in
      Meniere's disease and progressive hearing loss].
AB  - The Meniere's Disease and Progressive Hearing Loss were considered idiopathic.
      Both entities were produced by endo lymphatic hydrops and disruption of the
      membrane which contain type II collagen. The inner ear presented widely
      expression of type II collagen. These pathologies were probably autoimmune
      diseases. The aim of this work was to study the relationship of specific IgG to
      type II collagen in Meniere's disease, Progressive hearing loss, and compared
      with Sudden hearing loss patients, vascular vertigo patients and normal controls.
      Patients were divided by clinical findings in: 1 degree Meniere's disease (n:27),
      2 degrees Progressive Hearing loss (n:20), 3 degrees Sudden hearing loss (n:15),
      4 degrees Vascular Vertigo (n:9) and compared with normal controls (n:30) aged
      and sex matched. We have measured specific IgG to type II collagen by ELISA test.
      We considered positive the OD two or more SD above the mean of normal controls.
      RESULTS: 1 degree The Meniere's group presented IgG to type II collagen (+) in 22
      out of 27 patients, p < .025; 2 degrees The Progressive Hearing loss presented
      IgG to type II collagen in all cases (n:20), p < .0005. The Sudden Hearing loss
      presented IgG to type II collagen (-) in all cases (n:15) p < .00001 and Vascular
      Vertigo (n:9) presented IgG to type II collagen (-) in 8 out of 9 cases, p <
      .0005. These results suggest strongly the notion that Meniere's diseases and
      Progressive hearing loss have specific IgG to type II collagen and these
      conditions were ascribed with in autoimmune process.

PMID- 10883509
TI  - [Severe acute pancreatitis. Clinical and therapeutic contribution of diagnostic
      imaging].
AB  - Ultrasonography and dynamic tomography are used in the study of acute
      pancreatitis, thus helping to interpret the diverse anatomophysiopathologic
      variables. We present 41 patients studied by ultrasonography, on admission and
      twenty-four hours later or more. After seventy-two hours, a dynamic tomography
      was performed. We did a clinicotomographic correlation assessing necrosis, and
      multiple Ranson criteria, being complemented with the anatomopathologic study of
      specimens both in the complications and in the elective biliary surgery. There
      were three puncture aspirates for bacteriology. Eight (19.5%) patients developed
      local complications and four (9.75%) presented organ failure. Ultrasonography
      showed biliopancreatic hypertension in 45% of cases of biliary pancreatitis and
      was reversible in nature. Dynamic tomography was important in defining morphology
      and pancreatic necrotic involvement. There were two patients with intrapancreatic
      necrosis, six with intra and extrapancreatic necrosis and eleven patients who
      presents a dissemination of the process into the extrapancreatic tissues. The
      prevalence of glandular necrosis was 24%. Both, ultrasonography and dynamic
      tomography allowed to the identify a spectrum of lesions representative of
      cavitated extrapancreatic necrosis and enzymatic pericholecystitis. Likewise,
      they contributed to define medical treatment as well as indications,
      opportunities and approaches in the surgical and/or percutaneous treatment of
      septic complications.

PMID- 10883510
TI  - [Zenker diverticulum: therapeutic approach].
AB  - BACKGROUND: Pharyngoesophageal or Zenker diverticula are a few frequent pathology
      that could represent between 1 and 3% of the patients with dysphagia and their
      physiopathology even at present is scarcity clear. OBJECTIVE: Therapeutic
      procedures results about this pathology were analyzed. SETTING: Caraffa and Sucre
      Clinic. DESIGN: Retrospective observational study. METHOD: It analyzed 13
      patients operated by Zenker diverticula 9 of which were male and 4 were female
      sex with an average age of 55.6 years. Dysphagia occurred in 100% of the cases.
      Besides clinical finding the diagnosis was made evident by esophageal X-ray with
      contrast medium and endoscopy. Diverticulectomy by one stage through a left
      cervicotomy was the surgical procedure of choice. RESULTS: There was no surgical
      mortality. Related with morbility 2 patients presented fistulas managed medically
      and in other 2 patients abscesses of surgical wound occurred. The follow-up was
      carried on 6 months, 4 and 7 years respectively without relapses and with a good
      posterior evolution. CONCLUSIONS: Based on our short experience and the results
      attained we think the treatment of Zenker or pharyngoesophageal diverticulum by
      diverticulectomy through a left cervicotomy is safe and effective procedure to
      control this pathology.

PMID- 10883511
TI  - [Urinary incontinence prevalence in a population of 3552 urologic consultations
      and 1905 urodynamic studies].
AB  - OBJECTIVE: To establish the rate of urinary incontinence (UI) prevalence in a
      population of 3552 urologic consultations and 1905 urodynamic studies. MATERIAL
      AND METHODS: We conducted a revision of 3552 patients, 1905 of who were studied
      under pressure/flow urodynamic study estimating the rate of UI prevalence in
      terms of age, sex and type of incontinence. RESULTS: Out of 3552 consultations,
      586 patients were diagnosed with UI (16.5%). The same happened in 30.8% of the
      urodynamic studies (586/1905). The prevalence of Stress UI was 6.7%, la
      prevalence of urgency UI was 6.5% and finally the prevalence of Mixed IU was 2.6%
      80.7% were women 19.8% men. CONCLUSIONS: The prevalence of UI in our means was
      estimated in 16.5%. Four women out of every man suffer from this condition. Men
      suffer from urgency UI three times as much from Stress UI, mainly those who are
      over 60 years of age. On the other hand, women suffer from Stress UI three times
      as much from urgency UI, mainly those are over 40 year of age.

PMID- 10883512
TI  - [Localized nocardiosis].
AB  - Primary cutaneous nocardiosis is a rare disease. It is observed in people in
      contact with soil, after trauma. It is produced by an aerobic actinomyces which
      is found on the ground. We present a case of localized Nocardiosis placed on the
      left anatomical snuffbox. The patient was a 52 year old farmer. At the time of
      first consultation, the three year old lesions appeared as plaques which showed
      crusts and numerous suppurative fistulae, together with non painful nodules. He
      had no regional adenopathies. Material was taken for mycological direct and
      culture exams. A biopsy was taken for Anatomopathology. The patient remembered
      having suffered a trauma on the left hand by his tools in harvest time.

PMID- 10883513
TI  - [POEMS syndrome].
AB  - Poems syndrome is a rare multisystemic disorder. It manifestations are
      Polyneuropathy, Organomegaly, Endocrinopathy, and/or Edema, Monoclonal protein
      and changes in the Skin. (P.O.E.M.S.) Though some bibliography make no difference
      with osteoesclerotic myeloma it is considered a real syndrome. The polyneuropathy
      is customarily severe. Although high levels of immunoglobulins has been found in
      the poems, it has not been isolated a specific antibody that explain the
      polyneuropathy even though it is strongly suspected. The organomegaly,
      endocrinopathy, changes in the skin and other systems and involved organs could
      be in relationship to products secreted by plasmatic cells. We review the
      physiopathology and bibliography of the Poems, especially its neurological
      expression its nosologic location different from osteosclerotic myeloma and a
      possible relationship to the Herpes Virus 8. It was crossed in Medline the terms
      P.O.E.M.S. and syndrome and were obtained 271 abstracts that were all examined
      and finally selected the bibliography considerate meaningful for the objectives.
      It is presented briefly a case. P.O.E.M.S. is a syndrome that is associated to
      multiple plasma cell dyscracia, included the osteoesclerotic myeloma. Prognosis
      and the treatment vary with the underlying disease. As physiopathology of this
      syndrome is insinuated the action of the interleukins 1-beta (IL-1 beta) and 6
      (IL-6), the vascular growth endothelial factor (VGEF), the tumoral necrosis
      factor alpha (TNF-alpha) and antibodies anti-nerve. The P.O.E.M.S. is a syndrome
      with own identity. The Herpes Virus 8 may plays a key rol to uncover the Poems
      physiopathology.

PMID- 10883514
TI  - [Breast carcinoma metastasis in ileum-colon and gallbladder simulating
      inflammatory diseases].
AB  - The metastasis in the extrahepatic digestive system are not very frequent and
      their characteristic is appearing after a long latent period, which takes 3 to 20
      years, their symptoms are unspecific and appear to be inflammatory diseases or a
      second tumor. The most common histological subtype is the lobular carcinoma. Here
      we show you two cases of breast carcinoma metastasis, one in the ileum-colon and
      the other in the gallbladder. Both patient started showing symptoms, which led to
      the diagnosis was done in the surgical specimens where lobular carcinoma cells
      which infiltrated from the serosa to the mucosa were observed. The
      immunophenotype resulted to be BCA225, estrogen and progesterone positive. The
      treatment with radiotherapy, chemotherapy or hormonal therapy provides better
      life quality but the average chance of survival after the diagnosis is of a year.

PMID- 10883515
TI  - Fibromatosis mimicking clinically invasive breast carcinoma.
AB  - Our purpose is to report two cases of fibromatosis in two women of 34 and 48
      years old respectively that clinically appeared as a invasive breast carcinoma,
      particularly for the cutaneous retraction they showed. The histopathological
      diagnosis was done based on specimens studied with the common technique of
      paraffin embedding and Hematoxilin & Eosin staining. Both patients had firm
      poorly demarcated nodules with the histopathological pattern of classic
      fibromatosis. Mammary fibromatosis is an infrequent relapsing entity, not
      suspected in differential clinical diagnoses. The pathologist should bear it in
      mind, especially in frozen biopsies.

PMID- 10883516
TI  - [Research articles].
AB  - Since 1973, Revista Medica de Chile has classified biomedical and clinical
      prospective research papers in a Section named "Research Articles", while purely
      clinical and retrospective studies were classified into another Section, named
      "Clinical Experiences". This distinction seems no longer necessary, because both
      types of manuscripts are subjected to a uniform external peer-review system and
      their intrinsic quality is not a distinctive feature. Furthermore, the name of
      Sections where similar papers are classified by the major general clinical
      medicine journals is clearly non-uniform. Therefore, "Research Articles" and
      "Clinical Experiences" will from now on be included into a single Section:
      "Research Articles".

PMID- 10883517
TI  - [Lipoprotein particles LpA-I, LpA-I: A-II and LpB in coronary artery disease].
AB  - BACKGROUND: High density lipoproteins are an heterogeneous population of
      particles. Two main subpopulations have been identified, one contains Apo A-I and
      Apo A-II and is denominated LpA-I:A-II and another one contains only Apo A-I and
      is denominated LpA-I. AIM: To measure the concentrations of these particles in
      patients with stable coronary artery disease. PATIENTS AND METHODS: Serum lipids,
      A-I and B apolipoproteins, LpA-I, LpA-I:A-II and LpB particles were measured in
      73 men aged 33 to 82 years with angiographically documented coronary artery
      disease (CAD) and 33 control subjects aged 39 to 76 years. LpA-I, LpA-I:A-II and
      LpB were measured by a noncompetitive enzyme linked immunoassay using previously
      characterized monoclonal antibodies against ApoA-I, ApoA-II and apoB. RESULTS:
      Patients with CAD had significantly higher mean levels of LDL cholesterol than
      the control group (p = 0.038). The mean concentration of LpA-I particles in
      patients with CAD was significantly lower (p = 0.031) than in control subjects,
      while the concentration of LpA-I:A-II particles was significantly higher (p =
      0.016). The percentage of coronary stenosis correlated negatively with LpA-I and
      positively with LpA-I:A-II. The best relative risk (RR) indicator in these
      patients was LDL-cholesterol. The relative risk increases 2.5 fold when LpA-I
      falls below the cut-off level. Likewise, the relative risk increases 3-fold when
      LpA-I:A-II raises over the cut-off level. CONCLUSIONS: Our findings indicate that
      the quantification of LpA-I and LpA-I:A-II particles might allow a more accurate
      evaluation of the CAD risk than HDL cholesterol. LpA-I might represent the
      antiatherogenic fraction of HDL.

PMID- 10883518
TI  - [Syndrome of apparent mineralocorticoid excess caused by a deficiency of 11 beta
      hydroxysteroid dehydrogenase: clinical and genetic study in a Chilean family
      followed for 19 years].
AB  - An 11-year old girl was seen in 1981 with hypokalemia, low renin, low
      aldosterone, and severe hypertension. A medical adrenalectomy with dexamethasone
      and aminoglutethimide, and the blockade of mineralocorticoid receptors with
      spironolactone improved her condition, but the blockade of glucocorticoid
      receptors with RU-486 worsened it. An aldosterone infusion induced no changes. A
      sister was born in 1982 with similar findings. Both patients had an impaired
      ability to convert cortisol to cortisone after an oral load of 200 mg cortisol.
      In urine, an elevated ratio for metabolites of cortisol to metabolites of
      cortisone was found. These data suggested a defect in the activity of renal 11
      beta-hydroxysteroid dehydrogenase. Both parents were asymptomatic, phenotypically
      normal and non-consanguineous. Their urinary metabolites of cortisol and
      cortisone were normal before and after stimulation with ACTH. However, the mother
      reached a peak plasma cortisone concentration 3 SD below the mean reached by
      normal subjects after an oral 200-mg cortisol load, a fact that suggests that
      this test could be used to detect heterozygotes. The genetic studies revealed a
      homozygous mutation on exon 3 of the HSD11K gene, which by substituting TGC for
      CGC changes Arg 213 for Cys and induces a loss of 84% of the enzymatic activity
      in transfected cells. Both unrelated parents had the same heterozygous mutation.
      Both patients have been treated with dexamethasone but have also required
      spironolactone. The older sister has also required high doses of nifedipine to
      lower her blood pressure. After 19 years of follow-up, the older sister has
      become normotensive and normokalemic under therapy, and reached a final height of
      140 cm at age 17. The younger sister has increased her mean blood pressure at a
      rate of 1 mm Hg per year, in spite of treatment. Her final height is 143.5 cm.

PMID- 10883519
TI  - [Detection of pyrogenic exotoxin SpeA, SpeB and SpeC genes in Chilean
      streptococci isolates and their association with clinical manifestations].
AB  - BACKGROUND: The virulence of Streptococcus pyogenes is determined by a variety of
      structural molecules, toxins and complex enzymes. Pyrogenic exotoxins cause
      fever, erythematous reactions, cytotoxic and immunological effects. AIM: To
      assess the frequency of speA, SpeB and SpeC genes in Chilean Streptococcus
      pyogenes strains and their association with the invasiveness of infections.
      MATERIAL AND METHODS: The genes for pyrogenic exotoxins SpeA, SpeB and SpeC were
      determined by polymerase chain reactions in 114 strains of group A Streptococcus
      pyogenes isolated from Chilean patients with invasive or non invasive infections.
      RESULTS: The gene for SpeA was present in 30.7% of isolates, the gene for SpeB
      was present in 69.3% and the gen for SpeC in 44.7% of isolates. The gene for SpeA
      was present in 20 of 33 invasive infections and in 15 of 81 non invasive
      infections (p < 0.0001). On the contrary, the gene for SpeC was present in 11 of
      33 invasive infections and in 41 of 81 non invasive infections (p < 0.05). The
      frequency of speB was similar in invasive and non invasive infections.
      CONCLUSIONS: There is a clear relationship between the presence of SpeA genes and
      the severity of infections caused by Streptococcus pyogenes.

PMID- 10883520
TI  - [Thyroid function tests in normal pregnant women (third trimester) and in
      pregnant women with pregnancy cholestasis or with acute hepatitis].
AB  - BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a disease of unknown
      cause characterized by pruritus and biochemical cholestasis in the 3rd trimester
      of pregnancy. Its pathogenesis may be due to the interaction of abnormalities in
      the metabolism of estrogens and progesterone, while still unknown environmental
      factor (s) modulate the expressivity of a genetic predisposing trait. AIMS: To
      verify if thyroid function tests (TFT) are altered in ICP as in other hepatic
      diseases and whether a dietary iodine deficiency could be involved. MATERIAL AND
      METHODS: From 1983 to 1986, 13 normal pregnancies (3rd trimester), 26 ICP
      patients (with 30 pregnancies) and 4 patients with acute non-A non-B hepatitis in
      pregnancy, were studied. Serum T3, rT3, T4, fT4 and TSH (before and after TRH)
      were measured by RIA; in ICP patients, measurements were repeated in puerperium.
      Urinary 24 h iodine excretion was measured in normal pregnancies and in 6 ICP
      patients. RESULTS: In normal pregnancies, T3 (3.00 +/- 0.22 nmol/L) and rT3 (0.40
      +/- 0.03 nmol/L) were higher than the values detected in non-pregnant women;
      other TFT were unchanged. Urinary iodine excretion was normal in all individuals
      tested. Patients with acute hepatitis in pregnancy or with ICP had lower T3 than
      normal pregnancies (1.82 +/- 0.19 nmol/L in hepatitis; 2.24 +/- 0.12 nmol/L in
      ICP; p < 0.01) and higher rT3 (0.80 +/- 0.25 nmol/L in hepatitis; 0.54 +/- 0.05
      nmol/L in ICP; p < 0.05), while other TFT were unchanged. None of them had
      clinical signs of hypo or hyperthyroidism. A "euthyroid sick syndrome" was
      detected in 2 ICP patients and in 2 acute hepatitis in pregnancy. In puerperium
      of ICP patients, T3 and rT3 returned to levels in non-pregnant women.
      CONCLUSIONS: In ICP patients, TFT show similar trends than in more severe hepatic
      and non-hepatic diseases. Although thyroid binding-globulin was not measured in
      our patients, the pattern of TFT suggests that an impaired peripheral (hepatic?)
      deiodination of T4 is responsible for these changes. The influence of a dietary
      iodine deficiency can be ruled out.

PMID- 10883521
TI  - [Obesity and leptin association in three Chilean aboriginal populations].
AB  - BACKGROUND: Although there is a clear relationship between body mass index and
      leptin levels, few authors have addressed the possible influence of ethnic
      factors on these levels. AIM: To measure serum leptin in three different Chilean
      aboriginal populations. SUBJECTS AND METHODS: Fasting serum leptin and insulin
      levels were measured by radioimmunoassay in 345 rural mapuche individuals, 247
      rural aymara subjects and 162 urban mapuche subjects. A body mass index of 27.5
      kg/m2 was used as cutoff point to classify study subjects. RESULTS: Among the
      three ethnic groups, women had serum leptin levels three times higher than men.
      In all three ethnic groups, there was a significant association between leptin
      levels, body mass index and gender (r2 = 0.32 and 0.5 p < 0.001, in rural
      mapuche, r2 = 0.32 and 0.5 p < 0.001, in aymara and r2 = 0.24 and 0.49, p < 0.001
      in urban mapuche populations). No differences in leptin levels were observed for
      the interaction between age and insulin. The increments per quartile in leptin
      levels were lower among mapuche than aymara individuals. CONCLUSIONS: Rural
      mapuche individuals have a high frequency of obesity. However their leptin levels
      are lower than those of aymara or urban mapuche populations. The higher leptin
      levels observed in urban mapuche subjects could be due to environmental
      influences.

PMID- 10883522
TI  - [Carotid endarterectomy under regional anesthesia: initial experience].
AB  - BACKGROUND: Endarterectomy is the treatment of choice for internal carotid artery
      critical stenosis. Some authors have proposed that the use of regional anesthesia
      has advantages over general anesthesia. AIM: To report our initial experience
      with carotid endarterectomy under regional anesthesia. PATIENTS AND METHODS:
      Between 1998 and 1999, patients with critical carotid artery stenosis,
      asymptomatic or with transient and recovered symptoms, were selected. A C2, C3,
      C4 root deep cervical block and superficial block was performed, using a mixture
      of lidocaine and bupivacaine. A carotid endarterectomy with patch and without
      routine shunt insertion, with standard and neurological monitoring, was
      performed. RESULTS: During the study period, 94 carotid endarterectomies were
      done, 22 under regional anesthesia in 21 patients (12 male, age range 58-90 years
      old). Ninety five percent had hypertension, 52% smoked and 38% had renal
      dysfunction. One patient was converted to general anesthesia. Seventeen patients
      were discharged within 48 hours of the procedure and the rest, within 72 hours.
      There was no mortality or complications. CONCLUSIONS: Endarterectomy under
      regional anesthesia is less invasive, has excellent results and is well accepted
      by patients.

PMID- 10883523
TI  - [Safety and efficacy of celiprolol in hypertensive patients with chronic
      obstructive lung disease].
AB  - BACKGROUND: Third generation beta blockers have an intrinsic simpatico-mimetic
      activity and are cardioselective. Therefore, they should not have adverse
      bronchial effects and could even have a slight bronchodilator activity. AIM: To
      test the efficacy and safety of celiprolol in hypertensive patients with chronic
      obstructive lung disease. PATIENTS AND METHODS: Uncomplicated hypertensive
      patients with chronic obstructive lung disease received celiprolol during 12
      weeks. They were subjected to monthly clinical assessment and ventilatory
      function was measured on the basal period and at the end of the trial. RESULTS:
      During the study period, blood pressure fell significantly from 179 +/- 6/112 +/-
      8 to 161 +/- 4.7/98 +/- 1.6 mmHg. No changes were observed in forced expiratory
      volume in 1 s or in forced expiratory flow between 25 and 75% of the vital
      capacity. No subjective changes in respiratory function were reported during the
      trial. CONCLUSIONS: No changes in ventilatory function were observed in these
      patients with chronic obstructive lung disease, treated with celiprolol during 12
      weeks.

PMID- 10883524
TI  - [Survival of patients with esophageal cancer subjected to total thoracic
      esophagectomy].
AB  - BACKGROUND: Esophageal carcinoma has a dismal prognosis. Several authors have
      reported a very low survival in Chile. AIM: To report the survival of patients
      with esophageal carcinoma, subjected to esophageal resection. MATERIAL AND
      METHODS: Analysis of 108 patients subjected to thoracic esophageal resection
      between 1985 and 1996. Patients were classified according to the location of the
      tumor and its staging. RESULTS: Eleven patients died in the immediate
      postoperative period and 90 patients were followed. In 53 the exact cause of
      death was determined. Global five years survival was 29% and median survival was
      18 months. Survival was 100% in stage I tumors. Adjuvant therapy resulted in a
      better survival of stage III tumors. Survival of stage IV tumors was worst than
      stage I to III tumors. There was no survival difference between squamous
      carcinoma or adenocarcinoma. Tumors located in the superior third of the
      esophagus had a worst prognosis. Causes of death were mediastinic metastases,
      local recidivism, pleural or pulmonary metastases and less frequently, brain,
      bronchial or bone metastases. CONCLUSIONS: The survival of these, patients with
      esophageal carcinoma did not differ from the figures reported abroad.

PMID- 10883525
TI  - [Delirium in patients of an intermediate care unit: prospective study].
AB  - BACKGROUND: Delirium or acute confusional state is defined as an acute
      disturbance of consciousness and attention. Its prevalence among hospitalized
      patients fluctuates between 25 and 60%. AIM: To assess the prevalence and
      features of delirium in an intermediate care unit. PATIENTS AND METHODS: All
      patients admitted to intermediate care unit during a period of two months were
      assessed and followed. Delirium was assessed daily during the stay in the unit,
      using the Inouye Confusion Assessment Method. Delirium was classified as
      hyperactive if the patient required pharmacological or physical restraining
      methods. RESULTS: Sixty four patients, 32 female, aged 19 to 90 years old were
      assessed. Forty one percent had delirium. Of these, delirium started after
      admission in 46% and was hyperactive in 35%. Cognitive disturbances were
      ascertained by the health care team in 69% of patients with delirium. Age over 70
      years old and a history of dementia were defined as predisposing factors for
      delirium. Serum albumin was > 3.5 g/dl in 14 of 18 patients with and in 11 of 27
      patients without delirium (p = 0.04). The most frequent risk factors were
      systemic infections, metabolic disturbances and intracranial lesions. Physical
      restraining and neuroleptics were the most commonly used measures to deal with
      hyperactive patients. CONCLUSIONS: The prevalence of delirium found in this study
      is similar to that reported elsewhere, except for the high proportion of patients
      whose delirium started after admission.

PMID- 10883526
TI  - [Hungry bone syndrome: clinical experience in its diagnosis and treatment].
AB  - Hungry bone syndrome is a unusual complication of the postoperative period of
      primary hyperparathyroidism. This syndrome is characterized by hypocalcemia,
      hypophosphatemia and hypomagnesemia, due to an excessive bone remineralization.
      We report the clinical features, laboratory and therapy in four females (aged 39
      to 73 years old) with a long standing hyperparathyroidism, elevated alkaline
      phosphatases and decreased bone mineralization in two. The mean size of the
      adenoma was 2.9 +/- 1.1 cm. Hypocalcemia appeared between days 1 and 6 of the
      postoperative period. All were treated with calcium, calcitriol and magnesium at
      different timing and dosages. The mean hospitalization period was 19.8 +/- 2.1
      days. As reported previously, low bone mineralization and a large adenoma are
      risk factors for the syndrome. Serial monitoring of serum calcium and magnesium
      and an early supplementation of these minerals could prevent hypocalcemia and
      decrease the hospitalization time.

PMID- 10883527
TI  - [Renal scleroderma crisis. Role of scleroderma vasculopathy in the induction of
      cutaneous and visceral fibrosis in 2 cases].
AB  - Although fibrosis and vasculopathy coexist in most patients with progressive
      systemic sclerosis, it is not clear if these events are the result of an unique
      etiologic factor or if one is consequence of the other. We report two cases of
      progressive systemic sclerosis that evolved to a renal scleroderma crisis. A 36
      years old female presented with a Sjogren syndrome and painful subcutaneous
      nodules whose biopsy showed perivascular lymphocytic infiltration, perivascular
      thickening and normal skin. The ESR was 100 mm/h. She developed an hypertensive
      crisis and progressive renal failure, followed by a rapidly evolving progressive
      systemic sclerosis. The patient died in the course of this crisis. A 32 years old
      female with a progressive systemic sclerosis refractory to D-penicillamine
      treatment, receiving cyclosporin, presented a renal scleroderma crisis, that was
      successfully treated, with complete recovery of renal function. We highlight the
      different evolution of these cases, probably due to an early diagnosis and a
      better experience in the management of this condition.

PMID- 10883528
TI  - [Use of midodrine and frozen semen to treat semen transport disturbances. Report
      of 2 cases].
AB  - Retrograde ejaculation severely compromises male fertility. The use of
      sympathicomimetics for the treatment of this condition has poor results, except
      in patients with partial retrograde ejaculation, whose semen has a higher
      spermatozoa concentration. The semen of two patients with partial retrograde
      ejaculation was collected and frozen after the injection of a sympathicomimetic
      (Midodrine). The frozen/thawed samples were mixed with fresh semen recently
      ejaculated to obtain a minimal number of motile spermatozoa, and used for
      intrauterine insemination (> de 1 x 10(6) motile spermatozoa/ml). In both cases,
      pregnancies that developed satisfactorily, were obtained.

PMID- 10883529
TI  - [HERS study disturbs hormonal replacement therapy].
AB  - Cardiovascular protection of hormonal replacement therapy was considered a fact.
      The effects of estrogens on lipid levels and vascular health gave biological
      support to estrogen cardioprotection. The recently published HERS study showing
      no protective effects of estrogen and progesterone replacement therapy on the
      risk of myocardial infarction or coronary deaths is provoking perplexity. These
      surprising results may have several causes such as the use of progesterone, the
      associated use of cardioprotective agents or the short observation period.
      However, the study results scope is restricted to secondary prevention. These
      cannot be extrapolated to frequent conditions of postmenopausal women such as
      primary prevention or sequential schemes. Likewise, this investigation
      underscores the importance of a critical and continued evaluation of apparently
      well established therapeutic approaches.

PMID- 10883530
TI  - [Prevention and treatment of obesity since childhood: strategy to decrease the
      non transmissible chronic diseases in adult].
AB  - The prevalence of obesity among children and teenagers is increasing by 1.5% per
      year, probably due to a higher consumption of highly caloric foods and to
      physical inactivity. Hypercholesterolemia, increased insulin levels and high
      blood pressure of childhood obesity, precede atherosclerosis, coronary artery
      disease, diabetes and hypertension in adulthood. The prevention of childhood
      obesity is an efficient strategy to decrease the prevalence of non transmissible
      chronic diseases in the adult. The recommendations of experts committees for the
      prevention, diagnosis and treatment of childhood obesity are reviewed. They aim
      at a change in dietary habits and increasing physical activity. A well balanced
      healthy diet and a decrease in physical inactivity time will result in a
      successful treatment approach for obesity.

PMID- 10883531
TI  - [Determination of the in vitro activity of 2 glycopeptides (vancomycin and
      teicoplanin) against methicillin-resistant Staphylococcus aureus of intrahospital
      origin].

PMID- 10883532
TI  - [Geographic distribution maps of human genes in China].
AB  - The first set of geographic distribution maps of human gene in China are
      published, including 12 alleles: IB and IO of ABO system, m of MNS system, P1, Rh
      D, A1 and A11 of HLA system, Gm1;21 and Gm1,3;5 of immunoglobulin, AK1, deficient
      type of G6PD, and PTC test blindness gene t. These maps not only show the
      geographic distribution of alleles, but also can be used to study the origin and
      dispersal of some alleles, gene flow, and the effect of some selective factors on
      gene frequencies.

PMID- 10883533
TI  - [Molecular phylogeny of canidae using mitochondrial cytochrome b DNA sequences].
AB  - 372 bp mitochondrial cytochrome b DNA of blue fox, red fox, raccoon dog, and wolf
      were sequenced. Combined with the DNA fragments of dog, simien fox, and African
      wild dog, sequences were aligned and analyzed. There are 113 nucleotide sites
      substituted (30%). Molecular phylogenetic tree constructed by NJ method suggests
      that African wild dog is the earliest divergent. Wolf, dog, and simien fox which
      belong to genus Canis are combined into one branch which diverged earlier than
      raccoon dog, red fox and blue fox. Red fox is more related to blue fox than the
      other animals. The above result is in consistent with that of morphology.

PMID- 10883534
TI  - [Effects on organ-development of mouse embryo by inhibiting NOR activity].
AB  - It is reported here that the NOR activity of mouse embryonic cells treated with
      BrdU in Vitro. The NOR activity could be recovered after incubating the cells in
      the BrdU-free medium. The inhibition of NOR activity in the early and mid-term
      gestation led to abnormal development as follows: the increase of fetus abortion
      in vivo and death rate of newborn offsprings, causing a congenital blindness in
      the newborn offsprings. The main reason for the blindness is a contamination of a
      plenty of the untransparent granules with a size of 0.3 micron in diameter from
      the epithelial cells. The relationship between the transcription of 18S and 28S
      rRNA genes and the embryonic organ development is also discussed in this paper.

PMID- 10883535
TI  - [A study of ITS sequence as a molecular marker in the phylogeny of Drosophila
      nasuta subgroup].
AB  - A total of 1.1 kb including whole ITS (intertranscribed spacer), part of 5.8S
      rDNA and 2S rDNA were sequenced. The results reveal that D. pallidifrons, Taxon I
      and Taxon J share the same sequence, and D. albomicans and D. s. neonasuta have
      the other same one. Among the sequences, there were a handful of insertions,
      deletions and substitutions. Insertions and deletions occur mainly between
      outgroup and ingroups; yet only 1 insertion and 12 deletions were detected in D.
      niveifrons, and 1 deletion was found in D. s. sulfurigaster. Among all the
      substitutions in outgroup and ingroups, totally 55 transitions and 65
      transvertions were detected. The value of transition transvertion is quite
      different to that of mitochondrial genome. We applied parsimony and NJ methods to
      reconstruct the phylogenetic relationships of the 7 taxa. They show that D.
      niveifrons is on the basis of the trees, which suggests that it be less related
      to the rest; D. albomicans, D. s. neonasuta, D. pallidifrons, Taxon I and Taxon J
      are more related. We suggested that more related topology of D. s. sulfurigaster
      and D. s. neonasuta due to the specific evolution of ITS, yet not meaning their
      real relationships. Sequence variations and phylogeny analysis reveal that the
      ITS may be not an informative marker to nasuta subgroup. However, secondary
      structure analysis by using PCFOLD 4.0 reveals that the structure of the ITS is
      quite conservative; the stem-loop of ITS 3'-end may be an important structure of
      rDNA splicing.

PMID- 10883536
TI  - [Stable inheritance of hpt gene in transgenic rice plants mediated by biolistic
      bombardment].
AB  - Japonica rice cv 77170 was transformed with pBI222 carrying hygromycin
      phosphotransferase gene (hpt) by using biolistic bombardment and fertile
      transgenic rice plants were obtained. In T1 and most T2 generation the
      performance of hygromycin resistance was normal. Only in T2 progeny of SG-15 some
      lines showed decreased resistance. Mendelian inheritance of hygromycin resistance
      was showed as single dominant locus and proved by Southern blotting analysis in
      T1 and T2 generation of all transgenic plants. Multiple copies of hpt integrated
      into rice genome. These copies linked closely and inherited stablly. Msp I
      digested Southern blotting showed that methylation of hpt existed commonly in
      transgenic plants and their progeny, therefore uncomplete silencing of hpt in
      some T2 progeny of SG-15 was not associated with hpt methylation probably.

PMID- 10883537
TI  - [Major-polygene effect analysis of resistance to bacterial blight (Xanthomonas
      campestris pv. oryzae) in rice].
AB  - Five crosses between resistance and susceptible were analyzed to study major
      polygene effect using major-polygene mixed mode. The result showed that 3 of 5
      crosses were controlled by both major gene and polygene. In addition, there were
      large variation of additive effect, variance as well as heredity of major gene
      polygene in 3 crosses. Major gene was predominant in resistant variation, but
      durability should be considered. We suggested that construct major-polygene
      system be constructed in the long run in breeding program to ensure a durable and
      high level of resistance to constrain fluctuation of races of Xanthomonas
      campestris pv. oryzae population.

PMID- 10883538
TI  - [Genetical effect of different rye chromosomes on the acid phosphatase (Acph)
      secretion of common wheat roots under phosphorus starvation conditions].
AB  - The effects of different rye chromosomes on Acph secretion of common wheat roots
      under P starvation conditions were studied by using a set of Chinese Spring
      Imperial (CS-IMP) alien addition lines as materials. The Acph activity
      measurement results showed that P starvation is an induction factor for Acph gene
      expression; Different chromosomes of Imperial rye in Chinese Spring background
      has different effects on the secretion of Acph by corresponding addition line
      roots. Among them, chromosome 1R had the strongest promoting effect; The IEF
      diagram of Acph isozymes clearly demonstrated that chromosome 1R in rye genome
      carries P starvation inducible Acph gene(s).

PMID- 10883539
TI  - [Studies of the development of Triticum aestivum-Leymus racemosus translocation
      lines by pollen irradiation].
AB  - Pollens of 94G15 and 94G45, two wheat lines added to chromosome Lr.14 and Lr.2 of
      Leymus racemosus respectively were irradiated via 60Co-gamma rays and then used
      to hybridize with two common wheat varieties--Yangmai 5 and Mianyang 11. The five
      plants showing chromosome pairing between T. aestivum and L. racemosus at PMC MI
      stage were selected from seventeen examined plants of M1 progeny as the result of
      meiosis configuration analysis of chromosomes treated with Giemsa C-banding and
      fluorescent in situ hybridization. Among which, two T. aestivum-L. racemosus
      alien translocation lines--LW8(3)1 and LW11(3)1 were developed on the basis of
      further identification of M2 RTC chromosomes by C-banding and in situ
      hybridization. In addition, feasibility and effectiveness of the pollen
      irradiation in the development of T. aestivum-relatives alien translocations and
      the availability of the translocation lines of T. aestivum-L. racemosus are also
      discussed.

PMID- 10883540
TI  - [Isolation and verification of Triticum aestivum-Eremopyrum orientale addition
      lines and substitution lines by GISH].
AB  - Eremopyrum is a potential genus in wheat improvement. To breed T. aestivum-Er.
      orientale additional and substitutional lines, chromosome number of 96 BC2F3
      individuals were accounted. Fifteen plants with 2n = 43 and eight plants with 2n
      = 44 were checked out. GISH results of the individuals with 43 chromosomes showed
      that they blonged to three different monosomic additions. Two disomic additions,
      one double-monosomic addition, one trible-monosomic addition and one monosomic
      addition were found in the 2n = 44 individuals. One double-monosomic substitution
      and one monosomic substitution were obtained. We also proved that it is
      relatively easier to obtain addition lines in the selfing population than to
      obtain double-monosomic additions.

PMID- 10883541
TI  - [Study of genetic models of maize kernel traits].
AB  - Two sets of NCII mating design including 21 different maize inbreds were used to
      study the genetic models of five maize kernel traits--kernel length, width, ratio
      of kernel length and width, kernel thickness and weight per 100 kernels. Ten
      generations including P1, P2, F1, F2, B1, B2 and their reciprocal crosses RF1,
      RF2, RB1, RB2 were obtained. Three years' data were obtained and analyzed using
      mainly two methods: (1) precision identification for single cross and (2) mixed
      liner model MINQUE approach for diallel design. Method 1 showed that kernel
      traits were primarily controlled by maternal dominance, endosperm additive and
      dominance effect (maternal dominance > endosperm additive > endosperm dominance).
      Cytoplasmic effect was detected in one of the two crosses studied. Method 2
      revealed that in the total variance of kernel traits, maternal genotypic effect
      contributed more than 60%, endosperm genotypic effect contributed less than 40%.
      Cytoplasmic effect only existed in kernel length and 100 kernel weight, with the
      range of 10% to 30%. The results indicated that kernel genetic performance was
      quite largely controlled by maternal genotypic effect.

PMID- 10883542
TI  - [Estimation of biolistic transformation effect by transient expression of C1-R
      regulatory genes of anthocyanin biosynthesis].
AB  - In the present study, the transient expression of maize C1-R regulatory genes of
      anthocyanin biosynthesis in maize calli, wheat immature embryos, rice calli and
      tobacco leaves were described. C1-R regulatory genes could activate anthocyanin
      biosynthesis in vivo and the pigmented cells were visible. For major crops,
      including maize, wheat and rice, which were transformed mainly by biolistic
      method, C1-R genes were novel visible markers, and the expression was easier to
      detect than GUS gene. And these genes also worked well in transient expression in
      biolistic transformation system of tobacco leaves.

PMID- 10883543
TI  - [Studies of transgenic tobacco plants expressing beta-1,3-glucanase and chitinase
      genes and their potential for fungal resistance].
AB  - Plant bivalent expression vector pBLGC for basic tobacco beta-1, 3-glucanase and
      bean chitinase genes were constructed, and the tobacco tissue was transformed.
      Transgenic tobacco plants were carried out for analysis by PCR, PCR-Southern
      blot, Dot blot, Western blot, etc., and the results showed that some transgenic
      plants gave strong positive signal, it suggested that foreign genes have been
      integrated into tobacco genome, and expressed correctly. Fungal challenge with
      Alternaria alternata showed that transgenic plants were much more resistant to
      this pathogenic fungus.

PMID- 10883544
TI  - [Radiosensitivity of different ploidy pollen in poplar and its application].
AB  - Through investigation on germinating rate and process of unreduced diploidy
      pollen and monoploid pollen in Populus tomentosa x P. alba and P. tomentosa, it
      was proved that there were different radiosensitivities to 60Co gamma-ray among
      different ploidy pollen, i.e. the radiosensitivity of monoploidy pollen was two
      times higher than diploidy pollen. To overcome the problems of late germination
      and poor compatibility of diploidy pollen during fertilization, a certain dose of
      radiation can be applied to stimulating the diploidy pollen germination,
      meanwhile to restrain of kill some monoploidy pollen based on their different
      radiosensibilities. Therefore the rate of germination and faster germinating
      process of diploidy pollen on stigmas can be increased relatively to certain
      extent. The efficiency of radiation was proved by breeding practice. In the
      hybidization of (P. alba x P. glandulosa) x (P. tomentosa x P. bolleana), 3.8% of
      triploid could be produced by 1,470 rad treatment; while no triploid is examined
      in the control. 12.9% of triploids were produced by the treatment of 1,680 rad
      from the above cross.

PMID- 10883545
TI  - [Effects of cytochalasin B upon mitosis of Physarum polycephalum].
AB  - Cytochalasin B, known as a functional inhibitor of actin, was microinjected into
      naturally synchronous plasmodia of Physarum polycephalum, and the mitotic
      behaviours of both CB-treated specimens and the control were examined with light
      and electron microscopy. Mitosis in the CB-treated specimens began about 20 to 60
      minutes later than that of the control. It was delayed 35 minutes in the
      specimens treated with CB in the S phase of the cell cycle, and the delayed time
      was 20 minutes and 45 minutes, respectively. In the specimens treated with CB in
      early and middle G2 phase, the longest delay was 60 minutes found in the
      specimens treated in late G2 phase, indicating that mitosis was affected in
      Physarum polycephalum when the function of actin was inhibited by CB treatment.
      The CB-treated specimens and the control showed similarities in the process of
      mitosis and dynamic changes of nuclear structures, suggesting that the main
      effect of CB treatment upon mitosis may be to delay the triggering of the
      mitosis.

PMID- 10883546
TI  - Interactive psychoeducational group therapy in the treatment of authority
      problems in combat-related posttraumatic stress disorder.
AB  - The use of Interactive Psychoeducational Group Therapy to ameliorate authority
      problems of veterans with combat-related posttraumatic stress disorder is
      described. Despite the common occurrence of authority problems in this
      population, and the degree of damage they have caused in family, work, and legal
      domains, they are rarely specifically targeted by treatment interventions. A
      conceptual framework linking psychological trauma with distortions in authority
      relations is presented, followed by the format, procedures, and case examples of
      this form of group therapy. By uncovering the distorted beliefs associated with
      traumatic schemas as they emerge in the group interaction, the group therapist
      can first help the clients question their assumptions about authority, and then
      explore more adaptive behaviors. The need to examine in greater detail the causes
      and impact of authority problems among clients with posttraumatic stress disorder
      is emphasized.

PMID- 10883547
TI  - Integrating group psychotherapy and 12-step work: a collaborative approach.
AB  - Group therapists can expect to treat an increasing number of patients who are
      active in a 12-step program or other addiction-related self-help groups. The
      value of simultaneous participation in these two modalities has been recognized;
      12-step work supports abstinence necessary for the focus on emotional growth in
      psychotherapy. However, mere simultaneous participation in the two modalities
      fails to incorporate the benefits of a collaborative relationship where both
      modalities are used to support both abstinence and emotional growth. The conjoint
      approach to group and individual treatment is used to (a) argue for the
      possibility of a collaborative relationship between psychotherapy and a patient's
      12-step work, (b) understand the benefits and challenges to collaboration, and
      (c) provide guidelines for how to work collaboratively with a 12-step program.
      Illustrations are provided of typical issues raised by this type of collaborative
      relationship.

PMID- 10883548
TI  - The group psychotherapy movement at the millennium: some historical perspectives.
AB  - Although almost a century old, group psychotherapy has experienced an
      unprecedented expansion over the last 50 years. By the 1970s, human helping
      groups had found application in virtually all the human services, including the
      media. The growth of professional organizations for group work specialists was
      accompanied by a burgeoning literature and by accelerated research endeavors. The
      recent advent of the managed health care "revolution" has shaken the very
      foundations of this prospering group psychotherapy movement. Undue pressure from
      third-party payers for greater accountability and for cost-containment has come
      to threaten the traditional autonomy and dedication to quality of care by group
      therapy practitioners. Professional organizations have begun to meet these
      challenges by educational endeavors addressed at insurers, legislators, and the
      public. Current training programs and literature for clinicians have focused on
      the need for a new "business orientation" and on less costly group treatment
      measures (i.e., short-term and combined). Given group therapy's proven
      effectiveness, coupled with its practitioners' flexibility, the movement is bound
      to regain its secure footing at the dawn of the new millennium.

PMID- 10883549
TI  - An integrative model of stress management groups for women.
AB  - This article proposes an integrative model for stress management groups for
      women, representing a biopsychosocial point of view and drawing on theories of
      psychodynamic group psychotherapy, self-psychology, female development, and
      stress management. The basis of the model is an eight week traditional stress
      management group. The novel aspects of this integrative model are that it aims to
      increase the power of stress management groups for women by providing an
      articulated frame, attending to group process, promoting curiosity regarding
      resistance to behavior changes, encouraging the elaboration of affect, and giving
      importance to the role of relationships in each member's quest for self care and
      healthy entitlement.

PMID- 10883550
TI  - The group as selfobject: brief psychotherapy with women.
AB  - This article applies the theory of self psychology, which was developed by Heinz
      Kohut, to brief group psychotherapy. The article discusses the significance of
      the group as an expanded selfobject for individuals who do not have appropriate,
      available selfobjects in their environment. The article addresses the rationale
      for developing a 12-week women's group from a self-psychological perspective and
      illustrates key theoretical concepts in the beginning, middle, and end phases
      with group process. The role of the therapist in each phase of group development
      is emphasized.

PMID- 10883551
TI  - The detection of shame in group psychotherapy: uncovering the hidden emotion.
AB  - Shame, recently so extensively investigated in the individual and family therapy
      literature, has remained curiously underexplored in the group literature since
      Alonso and Rutan's noteworthy article on the subject in 1988. Shame is frequently
      bypassed because, as a result of its hidden nature, its presence is often not
      detected. This article strives to insure that shame does not go unaddressed. We
      catalogue and discuss six defenses that may suggest the subterranean workings of
      shame: (1) focusing on themes that stress similarities among members, (2)
      generating feelings of scorn and disdain, (3) avoiding here-and-now material, (4)
      inducing guilt, (5) transference reactions, and (6) preserving the illusion of
      the leader's infallibility. The best antidote for shame's neglect is a heightened
      readiness to detect it. Such detection is important because shame plays some role
      in many of our patients' complaints.

PMID- 10883552
TI  - A parenting group for women dealing with child sexual abuse and substance abuse.
AB  - This article describes a group developed to address the parenting needs of women
      dealing with child sexual abuse and substance abuse. A solution-focused 12-week
      group intervention is described, and the results of an evaluation are presented.
      Participants included 29 women who attended seven parenting groups. The results
      suggest that the group was perceived as beneficial by the women, who reported an
      increase in self-esteem, parenting satisfaction, and parenting self-esteem and an
      improvement in their attitudes toward their children.

PMID- 10883553
TI  - Risk factors for suicide in psychiatric outpatients: a 20-year prospective study.
AB  - To determine the risk factors for suicide, 6,891 psychiatric outpatients were
      evaluated in a prospective study. Subsequent deaths for the sample were
      identified through the National Death Index. Forty-nine (1%) suicides were
      determined from death certificates obtained from state vital statistics offices.
      Specific psychological variables that could be modified by clinical intervention
      were measured using standardized scales. Univariate survival analyses revealed
      that the severity of depression, hopelessness, and suicide ideation were
      significant risk factors for eventual suicide. A multivariate survival analysis
      indicated that several modifiable variables were significant and unique risk
      factors for suicide, including suicide ideation, major depressive disorder,
      bipolar disorder, and unemployment status.

PMID- 10883554
TI  - Comparison between one-session psychological treatment and benzodiazepine in
      dental phobia.
AB  - To compare the effects of a single session of psychological treatment and acute
      administration of benzodiazepine, 50 dental phobic patients were allocated either
      to psychological treatment, benzodiazepine, or no treatment for anxiety.
      Psychological treatment consisted of stress management training and imaginal
      exposure to phobic stimuli with homework assignments. Benzodiazepine was
      administered 30 min before dental treatment. Both treatment conditions led to
      less anxiety during dental surgery than did the control condition. Phobic
      patients in the benzodiazepine condition showed a relapse after dental treatment,
      whereas those in the psychological treatment condition showed further improvement
      until the follow-up 2 months later. Of the latter group, 70% continued dental
      treatment; only 20% and 10% returned in the benzodiazepine and control
      conditions, respectively.

PMID- 10883555
TI  - Violent thoughts and violent behavior following hospitalization for mental
      disorder.
AB  - Using a standardized schedule of questions, this study examined (a) the
      prevalence of self-report of violent thoughts by patients hospitalized for mental
      disorders compared with nonpatients, (b) the persistence of violent thoughts
      after discharge, and (c) the relation between patients' violent thoughts while
      hospitalized and violent acts within 20 weeks after hospital discharge. About 1/3
      of the patients reported thoughts of violence while hospitalized, more than twice
      the proportion found among nonpatients. Reporting violent thoughts in hospital
      was significantly related to engaging in violent acts within 20 weeks after
      discharge for non-White patients, patients without major mental disorder but with
      substance abuse diagnoses, patients with high symptom severity, and patients
      whose reports of violent thoughts persisted after discharge. Reporting violent
      thoughts was significantly related to measures of psychopathy, anger, and
      impulsiveness.

PMID- 10883556
TI  - Sexual abuse and sexual function: an examination of sexually relevant cognitive
      processes.
AB  - Participants were 61 sexually abused and 57 nonsexually abused women. The authors
      examined whether recent methodologies adopted from social-cognitive psychology
      might prove helpful in understanding the previously reported negative relation
      between childhood sexual abuse (CSA) and adult sexual function. In Part I, a card
      sort task was used to explore potential differences between sexually abused and
      nonsexually abused women in the categorization of positive/negative self
      information. In Part 2, sexually relevant information networks, believed to
      represent the way in which information is organized, accessed, and retrieved from
      memory, were compared. Sexually abused women differed from nonsexually abused
      women in the meanings they attributed to many sexuality-relevant concepts but not
      in how they compartmentalized positive/negative self-information. The findings
      provide insight into the cognitive processes by which CSA experiences might
      influence adult sexual function and provide a starting point for future research
      using this type of methodology.

PMID- 10883557
TI  - Cognitive-behavioral treatment of insomnia secondary to chronic pain.
AB  - Sixty participants with insomnia secondary to chronic pain were assigned randomly
      to either a cognitive-behavioral therapy (CBT) or a self-monitoring/waiting-list
      control condition. The therapy consisted of a multicomponent 7-week group
      intervention aimed at promoting good sleep habits, teaching relaxation skills,
      and changing negative thoughts about sleep. Treated participants were
      significantly more improved than control participants on self-report measures of
      sleep onset latency, wake time after sleep onset, sleep efficiency, and sleep
      quality, and they showed less motor activity in ambulatory recordings of
      nocturnal movement. At a 3-month follow-up assessment, treated participants
      showed good maintenance of most therapeutic gains. These results provide the 1st
      evidence from a randomized controlled trial that CBT is an effective treatment
      for insomnia that is secondary to chronically painful medical conditions.

PMID- 10883558
TI  - Dismantling cognitive-behavioral treatment for panic disorder: questioning the
      utility of breathing retraining.
AB  - Cognitive-behavioral treatment (CBT) protocols for panic disorder (PD) consist of
      a set of interventions that often includes some form of breathing retraining
      (BR). A controlled outcome study was designed to assess the necessity of BR in
      the context of a multicomponent CBT protocol. To accomplish this, patients with
      PD (N = 77) were randomly assigned to receive CBT with or without BR or to a
      delayed-treatment control. The main study hypothesis was that patients receiving
      BR would display a less complete recovery relative to the other active-treatment
      condition given that BR appears to be a more attractive (but less adaptive)
      option for some patients. Some data suggested that the addition of BR yielded a
      poorer outcome. However, findings were generally more consistent with treatment
      equivalence, questioning whether BR produces any incremental benefits in the
      context of other CBT interventions for PD.

PMID- 10883559
TI  - Psychophysiological, somatic, and affective changes across the menstrual cycle in
      women with panic disorder.
AB  - This study explored menstrual symptoms, somatic focus, negative affect, and
      psychophysiological responding across the menstrual cycle in women with panic
      disorder and controls. Women with and without panic disorder completed a
      psychophysiological task and self-report measures of menstrual symptoms, somatic
      focus, and negative affect on 4 occasions across 2 menstrual cycles (twice during
      intermenstrual and premenstrual phases). Women in the panic disorder group
      exhibited greater skin conductance magnitude and more frequent skin conductance
      responses to anxiety-provoking stimuli during the premenstrual phase than did
      controls. Compared to controls, women with panic disorder endorsed more severe
      menstrual symptoms relating to bodily sensations, anxiety sensitivity, state and
      trait anxiety, fear of body sensations, and illness-related concerns. The
      applicability of anxiety sensitivity to understanding the relation of menstrual
      reactivity and panic disorder is discussed.

PMID- 10883560
TI  - Commitment to treatment goals in prediction of group cognitive-behavioral therapy
      treatment outcome for women with bulimia nervosa.
AB  - The purpose of this study was to investigate potential client variables that
      predict favorable response to group cognitive-behavioral therapy in a sample of
      women (N = 143) seeking treatment for bulimia nervosa. Similar to findings of
      previous studies, bulimic symptom remission at end of treatment was predicted by
      baseline degree of bulimic symptom severity but not by depressive symptomatology
      or perfectionism. After these variables were controlled for, both pretreatment
      ratings of desire to discontinue bulimic behaviors and expected success
      significantly added to prediction of treatment outcome. The primary variable
      found to predict longer term outcome was symptom remission at the end of
      treatment and at the 1-month follow-up.

PMID- 10883561
TI  - Relation of the therapeutic alliance with outcome and other variables: a meta
      analytic review.
AB  - To identify underlying patterns in the alliance literature, an empirical review
      of the many existing studies that relate alliance to outcome was conducted. After
      an exhaustive literature review, the data from 79 studies (58 published, 21
      unpublished) were aggregated using meta-analytic procedures. The results of the
      meta-analysis indicate that the overall relation of therapeutic alliance with
      outcome is moderate, but consistent, regardless of many of the variables that
      have been posited to influence this relationship. For patient, therapist, and
      observer ratings, the various alliance scales have adequate reliability. Across
      most alliance scales, there seems to be no difference in the ability of raters to
      predict outcome. Moreover, the relation of alliance and outcome does not appear
      to be influenced by other moderator variables, such as the type of outcome
      measure used in the study, the type of outcome rater, the time of alliance
      assessment, the type of alliance rater, the type of treatment provided, or the
      publication status of the study.

PMID- 10883562
TI  - Mechanisms of change in multisystemic therapy: reducing delinquent behavior
      through therapist adherence and improved family and peer functioning.
AB  - The mechanisms through which multisystemic therapy (MST) decreased delinquent
      behavior were assessed in 2 samples of juvenile offenders. Sample 1 included
      serious offenders who were predominantly rural, male, and African American.
      Sample 2 included substance-abusing offenders who were predominantly urban, male,
      and Caucasian. Therapist adherence to the MST protocol (based on multiple
      respondents) was associated with improved family relations (family cohesion,
      family functioning, and parent monitoring) and decreased delinquent peer
      affiliation, which, in turn, were associated with decreased delinquent behavior.
      Furthermore, changes in family relations and delinquent peer affiliation mediated
      the relationship between caregiver-rated adherence and reductions in delinquent
      behavior. The findings highlight the importance of identifying central change
      mechanisms in determining how complex treatments such as MST contribute to
      ultimate outcomes.

PMID- 10883563
TI  - The San Diego Navy experiment: an assessment of interventions for men who assault
      their wives.
AB  - Three different 12-month interventions for servicemen who had been substantiated
      as having physically assaulted their wives were used and the outcomes examined.
      The 861 couples of the study were randomly assigned to 4 groups: a men's group, a
      conjoint group, a rigorously monitored group, and a control group. Cognitive
      behavioral interventions were implemented for the men's and conjoint groups, and
      outcome data were gathered from male perpetrators and female victims at roughly 6
      month intervals over the approximately 18-month experimental period. Data
      analyses revealed nonsignificant differences between the experimental groups over
      a variety of outcome measures.

PMID- 10883565
TI  - The reliability, validity, and unique contributions of self-report by adolescents
      receiving treatment for attention-deficit/hyperactivity disorder.
AB  - Participants were 36 adolescents diagnosed with attention-deficit/hyperactivity
      disorder (ADHD) who completed a summer treatment program. Self-report measures
      included the IOWA Conners Inattention/Overactivity and Oppositional/Defiant
      subscales, peer and staff interaction ratings, and a daily guess if the placebo
      or methylphenidate was given during a double-blind medication trial. Self-reports
      were reliable, and some of the self-report measures distinguished between placebo
      and methylphenidate conditions. However, the self-report measures exhibited weak
      correlations with observed frequencies of negative behavior and did not make a
      unique contribution beyond what was reported by adults. This study replicates
      previous findings that adolescents may be poor sources of information about ADHD
      symptoms, but adolescents receiving treatment for ADHD may be able to provide
      valid self-reports about negative social behavior.

PMID- 10883564
TI  - Diagnostic efficiency of neuropsychological test scores for discriminating boys
      with and without attention deficit-hyperactivity disorder.
AB  - A growing literature has documented group differences between boys with and
      without attention deficit-hyperactivity disorder (ADHD) on neuropsychological
      tests; however, whether or not such tests can discriminate individuals with ADHD
      from non-ADHD controls remains unclear. This study used conditional probability
      and receiver operating characteristic analyses to examine the efficiency of test
      based diagnostic discriminations in a large sample of referred boys with and
      without ADHD. Single neuropsychological tests had limited discriminating ability
      at various cutoff scores. When multiple tests were used together, prediction of
      ADHD status improved but overall diagnostic efficiency remained limited.
      Diagnostic efficiency did not differ when medicated and nonmedicated index
      children were considered separately. Results suggest that children with ADHD show
      variable deficits on neuropsychological tests of attention and executive
      functions. Impairments on multiple neuropsychological tests are predictive of
      ADHD, but normal scores do not rule out the diagnosis. The prognostic
      implications of variable neuropsychological deficits in children with ADHD
      require further investigation.

PMID- 10883566
TI  - Individual drinking changes following a brief intervention among college
      students: clinical significance in an indicated preventive context.
AB  - This study investigated the clinical significance of previously reported
      statistically significant mean reductions in drinking and related problems among
      college students in a randomized trial of a brief indicated preventive
      intervention (G. A. Marlatt et al., 1998). Data were analyzed over a 2-year
      follow-up for participants from a high-risk intervention group (n = 153), a high
      risk control group (n = 160), and a functional comparison group (n = 77). A risk
      cutpoint for each dependent measure was based on the functional comparison group
      distribution. Compared with the high-risk controls, more individuals in the high
      risk intervention group improved and fewer worsened, especially on alcohol
      related problems and, to a lesser extent, on drinking pattern variables. These
      data from a prevention context clarify the magnitude and direction of individual
      change obscured by group means.

PMID- 10883567
TI  - Effectiveness of an empirically based treatment for panic disorder delivered in a
      service clinic setting: 1-year follow-up.
AB  - The transportability of cognitive-behavioral therapy (CBT) for panic disorder to
      a community mental health center (CMHC) setting at 1-year follow-up was examined
      by comparing CMHC treatment outcome data with results obtained in controlled
      efficacy studies. Participants were 81 CMHC clients with a primary diagnosis of
      panic disorder with or without agoraphobia who completed CBT for panic disorder.
      Despite differences in settings, clients, and treatment providers, both the
      magnitude of change from pretreatment to follow-up and the maintenance of change
      from posttreatment to follow-up in the CMHC sample were comparable with the
      parallel findings in the efficacy studies. At follow-up, 89% of the CMHC clients
      were panic free and a substantial proportion of the sample successfully
      discontinued benzodiazepine use.

PMID- 10883568
TI  - Coding system of therapeutic focus on action and insight.
AB  - This study (a) used an established comprehensive process measure to uncover a
      latent pattern of therapeutic focus in cognitive-behavioral and psychodynamic
      interpersonal sessions; (b) used these results to develop the coding system of
      Therapeutic Focus on Action and Insight, which makes it possible to evaluate
      therapists' relative emphasis on the Constructing Meaning and Facilitating Action
      domains of in-session focus; and (c) evaluated its reliability and validity.

PMID- 10883569
TI  - Brief coping skills treatment for cocaine abuse: 12-month substance use outcomes.
AB  - Patients (N = 108) in a study of cocaine-specific coping skills training (CST),
      which was found to reduce cocaine use during a 3-month follow-up, were followed
      for an additional 9 months. CST involved coping skills training in the context of
      high-risk situations. Control treatment used meditation-relaxation. Both were
      added to comprehensive private substance abuse treatment. Patients in CST who
      relapsed had significantly fewer cocaine use days than did the control group
      during the first 6 months, then both conditions did equally well. Patients in CST
      also drank alcohol more frequently in the last 6 months than did contrast
      patients but did not differ in heavy drinking days. For cocaine use outcomes, no
      interaction of treatment was found with gender, education, route of
      administration, drug use severity, sociopathy, or depression. Implications
      include the need to investigate different lengths and combinations of treatment.

PMID- 10883570
TI  - Spouse abuse recidivism in the U.S. Army by gender and military status.
AB  - Recidivism by spouse abusers was investigated using records of offenders in the
      U.S. Army Central Registry. Recidivism by gender and military status (active-duty
      or civilian spouse) was compared over a 70-month period. Between fiscal years
      1989-1997, 48,330 offenders were identified in initial and recidivist incidents.
      Recidivism was analyzed by means of a Cox proportional hazard rate model,
      controlling for age, race, number of dependents, education, and substance abuse.
      Two different sets of survival curves were obtained: (a) Men were much more
      likely than women to have a recurrence and (b) within gender, civilians were more
      likely to have a recurrence than were active-duty military personnel. At 70
      months, 30% of the male civilian offenders and 27% of the male active-duty
      offenders had committed a subsequent spouse abuse incident compared with 20% of
      the female civilian offenders and 18% of the female active-duty offenders,
      controlling for other variables.

PMID- 10883571
TI  - Housing quality and mental health.
AB  - This study examined the potential link between housing quality and mental health.
      First, the development of a psychometrically sound, observer-based instrument to
      assess physical housing quality in ways conceptually relevant to psychological
      health is reported. Then 2 different studies, including a prospective
      longitudinal design, demonstrate that physical housing quality predicts mental
      health. Possible underlying psychosocial processes for the housing quality
      psychological distress link are discussed.

PMID- 10883573
TI  - The Mississippi Recovering Physicians Program.

PMID- 10883574
TI  - Coding concepts.

PMID- 10883572
TI  - Perceived exposure to peer and adult drinking as predictors of growth in positive
      alcohol expectancies during adolescence.
AB  - This study investigated the effects of change in exposure to peer and adult
      drinking on changes in positive alcohol expectancies during adolescence.
      Covariance and mean structure analysis were used to model change in the
      predictors and in alcohol expectancies in a sample of southern California
      schoolchildren followed from Grades 5 to 10 (N = 3,580). The sample was gender
      balanced and was predominantly White (51%) and Hispanic (28%). Exposure to peer
      drinking and rate of change in exposure to peer and adult drinking were found to
      predict the rate of change in alcohol expectancies. These effects were
      particularly strong between Grades 5 and 7, suggesting the need for early
      intervention aimed to prevent the increase in positive alcohol expectancies.

PMID- 10883575
TI  - Color-luminance relationships and the McCollough effect.
AB  - The McCollough effect is an orientation-specific color aftereffect induced by
      adapting to colored gratings. We examined how the McCollough effect depends on
      the relationships between color and luminance within the inducing and test
      gratings and compared the aftereffects to the color changes predicted from
      selective adaptation to different color-luminance combinations. Our results
      suggest that the important contingency underlying the McCollough effect is
      between orientation and color-luminance direction and are consistent with
      sensitivity changes within mechanisms tuned to specific color-luminance
      directions. Aftereffects are similar in magnitude for adapting color pairs that
      differ only in S cone excitation or L and M cone excitation, and they have a
      similar dependence on spatial frequency. In particular, orientation-specific
      aftereffects are induced for S cone colors even when the grating frequencies are
      above the S cone resolution limit. Thus, the McCollough effect persists even when
      different cone classes encode the orientation and color of the gratings.

PMID- 10883576
TI  - The role of the saccade target object in the perception of a visually stable
      world.
AB  - Although the proximal stimulus shifts position on our retinae with each saccade,
      we perceive our world as stable and continuous. Most theories of visual stability
      implicitly assume a mechanism that spatially adjusts perceived locations
      associated with the retinal array by using, as a parameter, extra-retinal eye
      position information, a signal that encodes the size and direction of the
      saccade. The results from the experiment reported in this article challenge this
      idea. During a participant's saccade to a target object, one of the following was
      displaced: the entire scene, the target object, or the background behind the
      target object. Participants detected the displacement of the target object twice
      as frequently as the displacement of the entire background. The direction of
      displacement relative to the saccade also affected detectability. We use a new
      theory, the saccade target theory (McConkie & Currie, 1996), to interpret these
      results. This theory proposes that retinal (as opposed to extra-retinal) factors,
      primarily those concerning the saccade target object, are critical for the
      detection of intrasaccadic stimulus shifts.

PMID- 10883577
TI  - Psychophysics of taste lateralization on anterior tongue.
AB  - There have been very few investigations of the spatial properties of taste
      stimuli localized to specific areas of the oral cavity. This is surprising, since
      the spatial localization of taste sensations may contribute to the overall taste
      percept, much as do quality, intensity, and the temporal characteristics of
      tastes. The difficulty in eliminating the confounding factor of a tactile
      sensation may partially account for the paucity of such studies, since a
      gustatory stimulus cannot be presented as a liquid without a tactile component.
      As a step toward understanding the localizability of gustatory sensations, we
      designed a yoked stimulator and an experimental procedure to control for tactile
      cues. Lateral discrimination was evaluated at the tip of the tongue with four
      taste stimuli (sodium saccharin, sodium chloride, citric acid, and quinine
      hydrochloride) by presenting a taste and a blank solution simultaneously at two
      locations on the tongue. We found that subjects could lateralize all four taste
      stimuli in the absence of any discriminative tactile cues. Subjects' ability to
      lateralize varied as a psychometric function of the stimulus concentration.
      Detection thresholds, measured in a forced-choice two-interval staircase
      procedure with the same yoked stimulator that was used in the lateralization
      task, were always lower than lateralization thresholds, and both lateralization
      and detection thresholds were correlated within subjects. Subjects were unable to
      lateralize taste cues on a nongustatory surface under the upper lip at the
      highest tested concentrations, at which performance was 100% on a gustatory
      surface (dorsal anterior tongue). These results show that (1) taste compounds can
      be lateralized in the absence of any discriminative mechanical cue (but only on
      the gustatory epithelium) and (2) although the localization of a compound does
      not logically require conscious detection of the taste (cf. blind sight),
      subjects always detected a taste when they were able to lateralize.

PMID- 10883578
TI  - Evidence for the duplex theory of tactile texture perception.
AB  - Three experiments are reported bearing on Katz's hypothesis that tactile texture
      perception is mediated by vibrational cues in the case of fine textures and by
      spatial cues in the case of coarse textures. Psychophysical responses when
      abrasive surfaces moved across the skin were compared with those obtained during
      static touch, which does not provide vibrational cues. Experiment 1 used two
      interval forced-choice procedures to measure discrimination of surfaces. Fine
      surfaces that were readily discriminated when moved across the skin became
      indistinguishable in the absence of movement; coarse surfaces, however, were
      equally discriminable in moving and stationary conditions. This was shown not to
      result from any inherently greater difficulty of fine-texture discrimination.
      Experiments 2 and 3 used free magnitude estimation to obtain a more comprehensive
      picture of the effect of movement on texture (roughness) perception. Without
      movement, perception was seriously degraded (the psychophysical magnitude
      function was flattened) for textures with element sizes below 100 microns; above
      this point, however, the elimination of movement produced an overall decrease in
      roughness, but not in the slope of the magnitude function. Thus, two components
      of stimulation (presumably vibrational and spatial) contribute to texture
      perception, as Katz maintained; mechanisms for responding to the latter appear to
      be engaged at texture element sizes down to 100 microns, a surprisingly small
      value.

PMID- 10883579
TI  - Perceptual anticipation in handwriting: the role of implicit motor competence.
AB  - In two experiments, perceptual anticipation--that is, the observer's ability to
      predict the course of dynamic visual events--in the case of handwriting traces
      was investigated. Observers were shown the dynamic display of the middle letter l
      excerpted from two cursive trigrams (lll or lln) handwritten by one individual.
      The experimental factor was the distribution of the velocity along the trace,
      which was controlled by a single parameter, beta. Only for one value of this
      parameter (beta = 2/3) did the display comply with the two-thirds power law,
      which describes how tangential velocity depends on curvature in writing
      movements. The task was to indicate the trigram from which the trace was
      excerpted--that is, to guess the letter that followed the specific instance of
      the l that had been displayed. In Experiment 1, the no answer option was
      available. Experiment 2 adopted a forced-choice response rule. Responses were
      never reinforced. When beta = 2/3, the rate of correct guesses was high
      (Experiment 1, P?correct? = .69; Experiment 2, P?correct? = .78). The probability
      of a correct answer decreased significantly for both smaller and larger values of
      beta, with wrong answers becoming predominant at the extremes of the range of
      variation of this parameter. The results are consistent with the hypothesis that
      perceptual anticipation of human movements involves comparing the perceptual
      stimulus with an internal dynamic representation of the ongoing event.

PMID- 10883580
TI  - A left hemisphere, but not right hemispace, advantage for tactual simultaneity
      judgments.
AB  - Hemispheric asymmetries for tactile simultaneity judgments were investigated in
      34 dextral adults. Pairs of vibrotactile stimuli with simultaneous or successive
      onsets were delivered unilaterally to the left or right hand. Participants made a
      forced-choice, bipedal response, indicating whether a stimulus was simultaneous
      or successive. The effect of hemispatial attentional biases was investigated,
      using ipsilateral (arms uncrossed) and contralateral (arms crossed) hand
      placements. Trials presented to the right hand were associated with fewer errors
      and a trend for faster response times than were those presented to the left hand.
      There was no asymmetry in response bias. Manipulations of hemispace did not
      affect the right hand advantage. These results confirm the existence of a left
      hemisphere temporal-processing advantage but fail to demonstrate that the
      asymmetry is the result of a rightward attentional bias. The implications of
      these results for absolute and relative models of hemispheric specialization are
      discussed.

PMID- 10883581
TI  - Why do pitched horizontal lines have such a small effect on visually perceived
      eye level?
AB  - In two experiments, visually perceived eye level (VPEL) was measured while
      subjects viewed two-dimensional displays that were either upright or pitched 20
      degrees top-toward or 20 degrees top-away from them. In Experiment 1, it was
      demonstrated that binocular exposure to a pair of pitched vertical lines or to a
      pitched random dot pattern caused a substantial upward VPEL shift for the top
      toward pitched array and a similarly large downward shift for the top-away array.
      On the other hand, the same pitches of a pair of horizontal lines (viewed
      binocularly or monocularly) produced much smaller VPEL shifts. Because the
      perceived pitch of the pitched horizontal line display was nearly the same as the
      perceived pitch of the pitched vertical line and dot array, the relatively small
      influence of pitched horizontal lines on VPEL cannot be attributed simply to an
      underestimation of their pitch. In Experiment 2, the effects of pitched vertical
      lines, dots, and horizontal lines on VPEL were again measured, together with
      their effects on resting gaze direction (in the vertical dimension). As in
      Experiment 1, vertical lines and dots caused much larger VPEL shifts than did
      horizontal lines. The effects of the displays on resting gaze direction were
      highly similar to their effects on VPEL. These results are consistent with the
      hypothesis that VPEL shifts caused by pitched visual arrays are due to the direct
      influence of these arrays on the oculomotor system and are not mediated by
      perceived pitch.

PMID- 10883582
TI  - Reliability and dimensionality of judgments of visually textured materials.
AB  - We extended perceptual studies of the Brodatz set of textured materials. In the
      experiments, texture perception for different texture sets, viewing distances, or
      lighting intensities was examined. Subjects compared one pair of textures at a
      time. The main task was to rapidly rate all of the texture pairs on a number
      scale for their overall dissimilarities first and then for their dissimilarities
      according to six specified attributes (e.g., texture contrast). The implied
      dimensionality of perceptual texture space was usually at least four, rather than
      three. All six attributes proved to be useful predictors of overall
      dissimilarity, especially coarseness and regularity. The novel attribute texture
      lightness, an assessment of mean surface reflectance, was important when viewing
      conditions were wide-ranging. We were impressed by the general validity of
      texture judgments across subject, texture set, and comfortable viewing distances
      or lighting intensities. The attributes are nonorthogonal directions in four
      dimensional perceptual space and are probably not narrow linear axes. In a
      supplementary experiment, we studied a completely different task: identifying
      textures from a distance. The dimensionality for this more refined task is
      similar to that for rating judgments, so our findings may have general
      application.

PMID- 10883583
TI  - The role of spatial frequency in cued shifts of attention between global and
      local forms.
AB  - It has been suggested that shifts of attention between global and local forms
      might be based on selection between, or differential activation of, low- and high
      spatial-frequency channels. In the present study, pretrial cues indicated which
      level (global or local) was likely to contain the target on each trial. There was
      a response time (RT) advantage for validly cued trials and an RT cost for
      invalidly cued trials relative to a neutral cue baseline. This cuing effect was
      the same for broadband stimuli and for contrast-balanced stimuli in which low
      spatial frequencies were eliminated. Thus, cued attentional shifts between global
      and local forms occur even when selection cannot be based on spatial frequency.

PMID- 10883584
TI  - The effect of luminance variation on the apparent position of an edge.
AB  - A gray outline against a white (or black) ground appears to deviate when one of
      the divided regions turns into black (white). The direction of shift is not
      predictable on the basis of luminance profile and polarity contrast of this part
      of contour, called gray edge (to indicate a stepwise gradient from black to gray
      and from gray to white). Rather, it appears to depend on the luminance profiles
      of the collinear regions: A gray edge shifts toward the dark side whenever
      collinear with a gray line traversing a white ground. The same gray edge takes
      the opposite direction whenever it extends against a black ground. This rule
      proved to be successful in predicting the illusory convergence of the sides of a
      square that formed the stimuli of the first experiment, but the magnitude of the
      phenomenon was affected by luminance ratios and polarity contrasts of the gray
      edges, in agreement with the findings of the experiments on gray or blurred edge
      misalignment. A second experiment tested some hypotheses predicting the combined
      effects of two or more distorting sources. These hypotheses, suggested by the
      physical theory of vector sum, were partially disproved. A new model is proposed
      that assumes different ways of integrating local distortions. The third
      experiment tested predictions of how distorting pulses in opposite directions
      combine. The illusory misplacement of edge studied in this experiment is proposed
      as the underlying phenomena of the cafe wall illusion, the hollow square
      illusion, and other illusory phenomena observed with blurred areas. A connection
      with the induction grid phenomena is hypothesized.

PMID- 10883585
TI  - Role of perceptual organization while attending in depth.
AB  - Seven experiments were conducted in order to explore the conditions under which
      visual attention can be allocated in depth. In each experiment, observers were
      cued to the most likely target location in stereoscopic depth displays, and
      targets could appear in either the cued location or in another location. In
      Experiments 1 and 2, we show that previous failures to observe effects of cuing
      in depth may have depended on the specific timing characteristics of the
      displays. In Experiments 3, 4, and 5, we eliminated the hypothesis, suggested by
      Experiments 1 and 2, that in order to allocate attention in depth, attention must
      be allocated to a specific object token. Experiment 6 provides evidence that, in
      the absence of other organizing information (e.g., color), attention can be
      allocated in depth on the basis of the surface information available in the
      display. Finally, in Experiment 7, we demonstrate that, although sufficient,
      surface information is not necessary for the allocation of attention; color
      supported the allocation of attention across multiple items that failed to fall
      on a single coherent surface in depth. Together, these findings suggest that
      attention in depth, like attention in two-dimensional displays, is determined by
      the perceptual organization of the display.

PMID- 10883586
TI  - Repetition effects in visual search.
AB  - Maljkovic and Nakayama (1994) demonstrated an automatic benefit of repeating the
      defining feature of the target in search guided by salience. Thus, repetition
      influences target selection in search guided by bottom-up factors. Four
      experiments demonstrate this repetition effect in search guided by top-down
      factors, and so the repetition effect is not merely part of the mechanism for
      determining what display elements are salient. The effect is replicated in
      singleton search and in three situations requiring different degrees of top-down
      guidance: when the feature defining the target is less salient than the feature
      defining the response, when there is more than one singleton in the defining
      dimension, and when the target is defined by a conjunction of features.
      Repetition does not change the priorities of targets, relative to distractors:
      Display size affects search equally whether the target is repeated or changed.
      More than one mechanism may underlie the repetition effect in different
      experiments, but assuming that there is a unitary mechanism, a short-term
      episodic memory mechanism is proposed.

PMID- 10883587
TI  - Object-based visual attention with endogenous orienting.
AB  - In a series of experiments, we examined covert orienting using endogenous cuing,
      in which attention is voluntarily directed toward a peripheral location. In one
      experiment, subjects were cued to attend to one end of an oblong object. They
      then detected targets on the cued object or elsewhere. In another experiment,
      subjects provided judgments of the relative temporal order of two flashes after
      their attention had moved endogenously. In a third experiment, subjects were
      directed to attend to an empty spatial location and subsequently discriminated
      features of objects that appeared at or near the locus of attention. In each of
      these situations, attentional orienting was object based, in the sense that
      nonattended locations that were on the cued object had an advantage over
      nonattended locations that were not on the object. The results are discussed in
      terms of their implications for object-based representations and the differences
      between exogenous and endogenous orienting of attention.

PMID- 10883588
TI  - Adaptation to time-compressed speech: phonological determinants.
AB  - Perceptual adaptation to time-compressed speech was analyzed in two experiments.
      Previous research has suggested that this adaptation phenomenon is language
      specific and takes place at the phonological level. Moreover, it has been
      proposed that adaptation should only be observed for languages that are
      rhythmically similar. This assumption was explored by studying adaptation to
      different time-compressed languages in Spanish speakers. In Experiment 1, the
      performances of Spanish-speaking subjects who adapted to Spanish, Italian,
      French, English, and Japanese were compared. In Experiment 2, subjects from the
      same population were tested with Greek sentences compressed to two different
      rates. The results showed adaptation for Spanish, Italian, and Greek and no
      adaptation for English and Japanese, with French being an intermediate case. To
      account for the data, we propose that variables other than just the rhythmic
      properties of the languages, such as the vowel system and/or the lexical stress
      pattern, must be considered. The Greek data also support the view that
      phonological, rather than lexical, information is a determining factor in
      adaptation to compressed speech.

PMID- 10883589
TI  - Neural network models of categorical perception.
AB  - Studies of the categorical perception (CP) of sensory continua have a long and
      rich history in psychophysics. In 1977, Macmillan, Kaplan, and Creelman
      introduced the use of signal detection theory to CP studies. Anderson and
      colleagues simultaneously proposed the first neural model for CP, yet this line
      of research has been less well explored. In this paper, we assess the ability of
      neural-network models of CP to predict the psychophysical performance of real
      observers with speech sounds and artificial/novel stimuli. We show that a variety
      of neural mechanisms are capable of generating the characteristics of CP. Hence,
      CP may not be a special model of perception but an emergent property of any
      sufficiently powerful general learning system.

PMID- 10883590
TI  - Noise increment detection in children 1 to 3 years of age.
AB  - Studies using burst comparison procedures to examine age-related changes in
      intensity discrimination have reported that the ability to discriminate
      differences in intensity does not reach maturity until late childhood. In the
      present study, developmental changes in intensity discrimination were examined in
      1- to 3-year-old children, using an increment detection paradigm. Children and
      adults detected increments in a continuous standard presented at three levels
      ranging from 35 to 55 dB SPL. Adults were also tested at lower levels of the
      standard in order to permit age comparisons at equivalent sensation levels.
      Standard stimuli were two-octave bands of noise centered at either 400 or 4000
      Hz, and increments were 200 msec in duration. Discrimination performance improved
      significantly with both age and level of the standard. For all age groups,
      performance was significantly better for high- than for low-frequency stimuli,
      but frequency-dependent differences in increment thresholds did not vary reliably
      with age. Age differences were largest at low levels of the standard. At the
      highest level (approximately 30 dB nHL), children's difference limens for both
      low- and high-frequency noise bands were adultlike by 3 years of age. These
      results suggest that the developmental time course of increment detection is more
      rapid than that previously reported in burst comparison studies.

PMID- 10883591
TI  - Perceptual magnet and phoneme boundary effects in speech perception: do they
      arise from a common mechanism?
AB  - The question of whether sensitivity peaks at vowel boundaries (i.e., phoneme
      boundary effects) and sensitivity minima near excellent category exemplars (i.e.,
      perceptual magnet effects) stem from the same stage of perceptual processing was
      examined in two experiments. In Experiment 1, participants gave phoneme
      identification and goodness ratings for 13 synthesized English /i/ and /e/
      vowels. In Experiment 2, participants discriminated pairs of these vowels. Either
      the listeners discriminated the entire range of stimuli within each block of
      trials, or the range within each block was restricted to a single stimulus pair.
      In addition, listeners discriminated either one-step or two-step intervals along
      the stimulus series. The results demonstrated that sensitivity peaks at vowel
      boundaries were more influenced by stimulus range than were perceptual magnet
      effects; peaks in sensitivity near the /i/-/e/ boundary were reduced with
      restricted stimulus ranges and one-step intervals, but minima in discrimination
      near the best exemplars of /i/ were present in all conditions.

PMID- 10883592
TI  - [Treatment strategy in complex hand injuries].
AB  - There are no clear definitions of serious or complex hand injuries in the
      literature. Multistructural injuries involving a vital risk to the affected part
      of the body part are usually classified as complex. The quality of the
      reconstruction, based on sound management principles, determines the aesthetic
      and functional outcome for the patient. The strategies basically consist of:
      Careful radical dbridement, thorough analysis of the defect and evaluation of
      lost functions, injury classification, Patient oriented reconstructive
      procedures, careful and realistic explanation of perspectives and risks to the
      patient. Following these principles will most likely achieve the planned
      objectives of treatment, such as, best possible restoration of form and function,
      cost-effective therapy, and early professional and social reintegration.
      Algorithmic approaches are an important aid in the clinical approach to these
      kinds of problems, making it possible to reach clear reproducible decisions that
      are amenable to standardization. Despite all individual decisions necessary to
      achieve optimal care, this standard theoretical framework will be able to improve
      the quality of care.

PMID- 10883593
TI  - [Unreamed antegrade humeral interlocking nailing].
AB  - In a prospective clinical study 111 fractures of the humerus in 109 consecutive
      patients were stabilized with unreamed antegrade interlocking nailing. 97
      patients were evaluated with individual follow-up, in the mean at 24.2 months
      postoperatively. Mean fracture consolidation time was 12.3 weeks (9-16 weeks).
      Five patients presented a non union. At follow-up 19 patients had a limitation in
      motion of the shoulder, in the mean with 20% compared to the opposite side. Eight
      patients had permanent shoulder pain, in nine patients shoulder pain occurred
      during manual strain of the upper limb. Neither limitation of motion nor pain at
      the elbow region was present in all cases at follow-up. Ultrasound examination
      revealed in six cases a lesion of the rotator cuff, which was linked in these
      cases with permanent pain at the shoulder joint. In five patients a prominent
      nail tip at the entrance point caused a lesion of the rotator cuff with
      impingement syndrome. Eight out of nine preoperative palsies of the radial nerve
      recovered within a mean period of 4.3 months without operative measurements.
      Unreamed antegrade interlocking nailing of humeral fractures is a safe technique
      regarding consolidation rate with advantages regarding early mobilization of the
      upper limb. Careful suturing of the rotator cuff and countersinking of the
      proximal nail tip at the entrance point is a prerequisite in avoiding permanent
      lesions of the rotator cuff and shoulder pain.

PMID- 10883594
TI  - [Epidemiology of the severely injured patient. A prospective assessment of
      preclinical and clinical management. AG Polytrauma of DGU].
AB  - The severe multiple trauma is of extraordinary medical and social and economical
      importance. Nevertheless there exist only a few german data to describe these
      patients. The aim of the study was an epidemiological analysis of 2069 patients
      of the Trauma Registry of the German Society of Trauma Surgery, recorded from
      1993-1997. A descriptive kind of analysis of the incidence of injuries and
      complications of this collective was done and the amount of therapeutic means
      examined. Most patients (56.7%) were traffic victims, almost all patients
      suffered from blunt trauma. The relation male to female was 2.6:1, the average
      Injury Severity Score 22.2 +/- 13.1 points, the average age was 38.5 +/- 18.7
      years. Chest trauma was the most frequent significant injury (AIS > or = 3
      points, 44.5%), followed by severe head injury (39.2%) which was the most
      important reason for early lethality (death < or = 24 h after trauma, 51.7% of
      all deceased) and the total hospital lethality (18.6%). 68.9% of the patients
      showed injuries of the extremities. Patients were admitted to hospital in 71.7%
      in times of stand-by service (between 4 p.m. and 8 a.m., weekends, holidays) and
      required (median) 4 days ventilation, 6 days ICU treatment and stayed in hospital
      19 days. Complications recorded were organ failure (lung 22.0%, circulation
      18.7%, liver 9.6%, kidney 3.1%) and sepsis (11.6%). The presented epidemiological
      analysis is a comprehensive description of a large collective of multiple
      traumatized patients. The current data of the Trauma Registry of the German
      Trauma Society can be used to answer scientific, clinical and economical
      questions and for quality management.

PMID- 10883595
TI  - [Fractures of the upper extremity in restrained automobile front seat passengers.
      Injury pattern and incidence in relation to accident mechanism].
AB  - During 1985 and 1995, 3,260 restrained car drivers (1,228 front seat passengers)
      were injured in 9,380 crashes involving cars. 179 (5.5%) (front seat passengers:
      53, 4.3%) of those sustained fractures, of the arm. Among the 384 single
      fractures the hand (25%), wrist (23%) and forearm (23%) were affected most often,
      elbow (9%), upper arm (10%) and shoulder (10%) rather seldom. Half of the
      evaluated fractures of the long tubular bones were type A-fractures due to the AO
      classification and the other two quarters, respectively type B- and C-injuries in
      each case. 16% were open fractures. No considerable differences of the injury
      mechanism were found comparing drivers and front seat passengers. Since over half
      of all fractures resulted from a direct impact to the hand and/or arm,
      modifications are necessary in order to improve the energy absorption by means of
      padding the dashboard and the inner door. The use of side- and front-airbags
      could serve as an additional auxiliary equipment, as long as it doesn't induce a
      supplemental stress, through unfolding of the airbag.

PMID- 10883596
TI  - [Quality of life improvement (SF-36) after implantation of a knee
      endoprosthesis].
AB  - From a group of 41 consecutive patients receiving an endoprosthetic knee
      replacement 35 patients underwent complete pre- and postoperative documentation
      of life quality in the short term follow-up. The comparison of pre- and
      postoperative life quality assessment with the SF-36 form showed significant
      differences on the 5% level for the categories "somatic pain" and "psychological
      wellness". The parameter "somatic functionality" showed with a P-value of 0.0616
      almost significant improvement. The other parameters also showed improved values
      without reaching statistical significance. In summary, after implantation of a
      total knee replacement an improvement of life quality can be documented.

PMID- 10883597
TI  - [Mechanical properties of suture materials for anchoring cruciate ligament
      transplants].
AB  - The fixation of hamstring grafts in ACL reconstruction requires a connector
      device. During the process of ingrowing the graft stability depends entirely on
      the fixation. The following study focused on the mechanical conditions of no 6
      Ethibond, 5 mm Mersilene tape and 5 mm Polylene tape. The material were tested as
      loops with a length of 30 mm including the knot similar to intraoperative
      conditions. The ultimate tension load and elongation of the conditioned and
      unconditioned loops were investigated under cyclic load of 50 N and 100 N using a
      tension load machine. The ultimate tension load increased significantly only for
      Mersilene from 416 N to 462 N. However, the highest ultimate tension load showed
      Polylene with 479 N. The oscillating load up to 100 N revealed for unconditioned
      loops an elongation of 4.1 mm for Ethibond, 2.9 mm for Polylene and 5.4 mm for
      Mersilene. The elongation decreased significantly for the conditioned loops to a
      maximum of 1.4 mm. Concerning the amplitude during the period of oscillating load
      there was found a significant reduction as well. Based on our results Polylene
      showed the best mechanical properties. Regardless the intraoperatively used
      material we advocate the conditioning of the loops before anchoring the hamstring
      graft in ACL reconstruction.

PMID- 10883598
TI  - [Effect of various bone disinfection and sterilization methods on osteoblast
      function. A comparative in vitro study].
AB  - All sterilization and disinfection procedures for bone grafts are different in
      regard to influence of bone graft features, which may influence the function of
      different cell types. We used an in-vitro approach to assess the influence of
      bone matrix, which was sterilized or disinfected, on osteoblastic activities in
      vitro by simulating a cell-transplant-interface. Primary bovine osteoblast cell
      cultures were established from periosteum. Bone graft specimens made of bovine
      cortical bone (O 15 mm, 300 microns thickness) were treated in 5 different ways:
      autoclaved, ethylene-oxide-sterilized, demineralized and low-temperature-plasma
      sterilized (DEM-LTP), chemically sterilized (modified Tutoplast method), and 80
      degrees C-temperature disinfected. The following cell function parameters were
      assayed: plating efficiency proliferation by measuring the DNA-content, and MTT
      activity, soluble protein and extracellular matrix synthesis, alkaline
      phosphatase, and osteocalcin expression. All disinfected bone grafts were
      biocompatible with primary periosteal osteoblasts. Measured cell activities upon
      bone specimens showed better results than cells of the plastic surface control.
      The DEM-LTP-bone showed better results in comparison to other groups, and
      stimulated the proliferation and differentiation.

PMID- 10883599
TI  - [Blood replacement in trauma surgery].

PMID- 10883600
TI  - [Tuberculous coxitis. Case report and surgical treatment].
AB  - The possibility of a specific origin of joint infection should be considered in
      finding the diagnosis. This is demonstrated in a case of tuberculosis of the hip
      treated in the Dept. of Trauma Surgery in collaboration with the Medical Dept. of
      the Klinikum Minden. Microbiological and imaging examinations are essential to
      plan and perform a combined therapy of hip arthroplasty and concommitant medical
      antituberculous therapy. In accordance to a literature review, this procedure
      proved successful for both eliminating the local infection and the functional
      outcome of the operation.

PMID- 10883601
TI  - [The de-epithelialized turnover flap for defect coverage iin the area over the
      Achilles tendon and over the lateral malleolar region].
AB  - The deepithelialized "turn-over-flap" is a reversed dermis flap. The pedicle of
      the flap remains intact. The mobile upper part of the flap is turned over the
      defect and the pedicle itself. A mesh graft covers both, the flap and the donor
      side. Two case reports will present the principles of the flap design and the
      clinical outcome of a patient with a defect over the lateral malleolar region and
      a patient with a defect over the Achilles tendon.

PMID- 10883602
TI  - [Non-Hodgkin lymphoma as differential spondylodiscitis diagnosis].
AB  - This case presents the history of a 56-year-old patient suffering from low back
      pain for a period of several weeks. The radiological und histopathological
      examination showed hints for a spondylodiscitis of the fifth lumbar vertebra. Due
      to a progressive destruction of the fifth vertebra a ventral stabilisation was
      performed. Again the histological examination showed the characteristics of an
      unspecific spodylodiscitis. The last biopsy, taken during the explantation of the
      fixateur interne showed a high malignant lymphoma. A course of chemotherapy was
      started following the CHOP-Protocol accompanied by radiotherapy. This case
      demonstrates that meticulous clinical examination as well as advanced
      radiological techniques can fail in rare differential diagnosis of
      spondylodiscitis.

PMID- 10883603
TI  - [Dilatation technique with the TNS (transcutaneous nail insertion system) for
      minimally invasive implantation of intramedullary nails at the proximal femur].
AB  - A new technique of a minimally invasive approach to the proximal femur was
      developed for the management of per- and subtrochanteric fractures using
      intramedullary nail blade systems. For creating the entry portal at the proximal
      femur a transcutaneously applied Kirschner-wire is used. Subsequently, a new
      developed trocar system (TNS) for the protection of the soft tissue during
      reaming procedures is placed via a small cutaneous incision. The reaming of the
      femoral shaft can be performed through this trocar system. A new targeting jig
      especially adapted to the gliding nail was used in this first series. From
      December 1998 to June 1999 12 patients were treated with this new technique in
      the Department of Trauma Surgery of the Philipps-University in Marburg. The mean
      age of the 8 female and 4 male patients was 78 (+/- 12) years. The majority of
      the total group were old patients with a mean ASA score of 3-4. Relevant
      intraoperative complications using the new dilatation approach were not observed.
      All patients were mobilised after few days. Postoperative complications or
      infections were not found. In the clinical practice of the management of per- and
      subtrochanteric femoral fractures the new dilatation approach has proved to be
      more comfortable and minimally invasive than the standard technique existing to
      date.

PMID- 10883604
TI  - [Recommendations for diagnosis and expert assessment of traumatic rotator cuff
      lesions].
AB  - Traumatic rotator cuff lesions are a very rare condition. However, this article
      represents a comprehensive survey according to current knowledge on anatomy,
      biomechanics, and pathogenesis of rotator cuff pathology. Because of the
      relatively high prevalence of degenerative changes with increasing age, including
      partial and complete rotator cuff tears, it may be difficult to demonstrate the
      causality of an acute traumatic rotator cuff tear. Therefore, a catalogue of
      potential adequate and inadequate trauma mechanisms is proposed. Emphasis is also
      placed on posttraumatic diagnostic steps following persistent rotator cuff
      deficient shoulder function (e.g., ultrasound, MRI). From a legal aspect (e.g.,
      private accident insurance, workers compensation claim), different minor and
      major criteria are defined, which could help experts to judge the causality of
      posttraumatic rotator cuff deficiency. These criteria mainly refer to distinct
      details concerning patients' history, trauma mechanism, primary clinical
      appearance, and diagnostic findings.

PMID- 10883605
TI  - Facial animation in children with Mobius syndrome after segmental gracilis muscle
      transplant.
AB  - Mobius syndrome is a complex congenital anomaly involving multiple cranial
      nerves, including the abducens (VI) and facial (II) nerves, and often associated
      with limb anomalies. Muscle transplantation has been used to address the lack of
      facial animation, lack of lower lip support, and speech difficulties these
      patients experience. The purpose of this study was to investigate the results of
      bilateral, segmental gracilis muscle transplantation to the face using the facial
      vessels for revascularization and the motor nerve to the masseter for
      reinnervation. The outcome of the two-stage procedure was assessed in 10
      consecutive children with Mobius syndrome by direct interview, speech assessment,
      and oral commissure movement. Preoperative data were collected from direct
      questioning, viewing of preoperative videotapes, notes from prior medical
      evaluations, and rehabilitation medicine and speech pathology assessments. All of
      the patients developed reinnervation and muscle movement. The children who
      described self-esteem to be an issue preoperatively reported a significant
      posttransplant improvement. The muscle transplants produced a smile with an
      average commissure excursion of 1.37 cm. The frequency and severity of drooling
      and drinking difficulties decreased postoperatively in the seven symptomatic
      children. Speech difficulties improved in all children. Specifically, of the six
      children with bilabial incompetence, three received complete correction and three
      had significant improvement. Despite the length and complexity of these
      procedures, complications were minimal. Muscle transplantation had positive
      effects in all problematic areas, with a high degree of patient satisfaction and
      improvement in drooling, drinking, speech, and facial animation. The surgical
      technique is described in detail and the advantages over regional muscle
      transfers are outlined. Segmental gracilis muscle transplantation innervated by
      the motor nerve to the masseter is an effective method of treating patients with
      Mobius syndrome.

PMID- 10883606
TI  - Deep inferior epigastric perforator dermal-fat or adiposal flap for correction of
      craniofacial contour deformities.
AB  - Craniofacial contour deformities are difficult to reconstruct. This article
      summarizes the authors' use of deep inferior epigastric perforator dermal-fat or
      adiposal flaps in eight patients with such deformities. Of these patients, three
      had traumatic craniofacial or facial deformities, one had congenital craniofacial
      deformity, two had hemifacial atrophy (one because of radiation), one had
      hemifacial microsomia, and one had localized frontonasal lipodystrophy. Stable
      restoration of the facial contour was achieved in all eight patients. The
      advantages of this flap are numerous. It has minimal donor-site morbidity,
      because the rectus abdominis muscle is preserved as a whole, and it accommodates
      pregnancy in female patients. Simultaneous elevation of this flap during
      preparation of the recipient site makes it possible to complete surgery in a
      shorter time than with the scapular flap. Furthermore, a considerable amount of
      the superficial or deep fatty layer can be removed primarily, making a bulky flap
      into a thinner one. This flap also allows the use of a large transverse abdominal
      ellipse of skin, fat, and Scarpa's fascia with abdominoplasty closure.
      Conversely, it requires a technically difficult dissection of the muscle
      perforator and skin grafting of donor defects in patients with a large dermal-fat
      flap. Also, additional minor operations may be necessary to reduce fat volume
      around the perforator. Ultimately, the deep inferior epigastric perforator
      adiposal flap seems to be suitable for craniofacial contouring surgery. It is
      especially indicated for use in children and female patients who are expecting to
      have children.

PMID- 10883607
TI  - Chiari malformation, cervical spine anomalies, and neurologic deficits in
      velocardiofacial syndrome.
AB  - The purpose of this investigation was to evaluate the prevalence of Chiari
      malformation, cervical spine anomalies, and neurologic deficits in patients with
      velocardio-facial syndrome. This study was a prospective evaluation of 41
      consecutive patients with velocardiofacial syndrome, documented by fluorescence
      in situ hybridization, between March of 1994 and September of 1998. The 23 girls
      and 18 boys ranged in age from 0.5 to 15.2 years, with a mean age of 6.7 years.
      Nineteen patients were assessed with magnetic resonance imaging, 39 underwent
      lateral cephalometric radiography, and all patients were examined for neurologic
      deficits. Eight of 19 patients (42 percent) had anomalies of the craniovertebral
      junction, including Chiari type I malformations (n = 4), occipitalization of the
      atlas (n = 3), and narrowing of the foramen magnum (n = 1). One patient with
      Chiari malformation required suboccipital craniectomy with laminectomy and
      decompression. Fourteen of 41 patients (34 percent) had demonstrated neurologic
      deficits; 10 patients (24 percent) had velar paresis (6 unilateral and 4
      bilateral). Chiari malformations, cervical spine anomalies, and neurologic
      deficits are common in velocardiofacial syndrome. Because these findings may
      influence the outcome of surgical intervention, routine assessment of patients
      with velocardiofacial syndrome should include careful orofacial examination,
      lateral cephalometric radiography, and magnetic resonance imaging of the
      craniovertebral junction.

PMID- 10883608
TI  - Complex facial nevi: a surgical algorithm.
AB  - Sixty-six children with large congenital nevi of the face were surgically managed
      in our center during the last 8 years. All patients with a lesion that posed a
      reconstructive challenge were included in the study. None could be effectively
      dealt with by excision and simple primary closure. To simplify description and
      evaluation, the patients were divided into three groups. Group I had 15 patients
      with relatively small lesions (1- to 3-cm maximal diameter) that were confined to
      one aesthetic unit of the face and could be reconstructed in one stage.
      Reconstruction was usually achieved by using local skin flaps or with full
      thickness skin grafting. Group II had 28 patients with medium-sized lesions (3-
      to 12-cm maximal diameter) that involved one or two aesthetic units and required
      not more than two stages for reconstruction. These patients usually needed either
      serial excisions and/or skin grafting or a two-stage tissue expansion procedure
      (insertion of tissue expanders and reconstruction). Group III had 23 patients
      with very large lesions (over 12 cm in maximal diameter), some covering half of
      the face and thus involving several aesthetic units and requiring multiple stages
      for reconstruction. These patients required a combination of tissue expansion
      procedures, large faciocervical and scalp/forehead skin flaps, full-thickness
      skin grafting, and serial excisions for reconstruction. The anatomic distribution
      of the lesions over the various aesthetic units is described, as are the
      reconstructive techniques with advantages and disadvantages of each, reflecting
      on outcome. The approach to the larger complex lesions is detailed. Based on our
      experience, a reconstructive algorithm is proposed.

PMID- 10883609
TI  - Nasal reconstruction based on aesthetic subunits in Orientals.
AB  - Reconstruction based on the aesthetic subunit principle has yielded good
      aesthetic outcomes in patients with moderate to severe nasal defects caused by
      trauma or tumor resection. However, the topographic subunits previously proposed
      are often unsuitable for Orientals. Compared with the nose in white patients, the
      nose in Orientals is low, lacks nasal muscle, and has a flat glabella; the
      structural features of the underlying cartilage and bone are not distinctly
      reflected in outward appearance. The authors devised aesthetic subunits suitable
      for Orientals, and they used these units to reconstruct various parts of the
      nose. The major difference between these units and those presented previously is
      the lack of soft triangles and the addition of the glabella as an independent
      unit. The authors divided the nose into the following five topographic units: the
      glabella, the nasal dorsum, the nasal tip, and the two alae. The border of the
      nasal dorsum unit was extended to above the maxillonasal suture. The basic
      reconstruction techniques use a V-Y advancement flap from the forehead to
      reconstruct the glabella, an island flap from the forehead to reconstruct the
      nasal dorsum and nasal tip, a nasolabial flap to reconstruct an ala, and a malar
      flap to reconstruct the cheek. A combination of flaps was used when the defect
      involved more than one unit. This concept was used for nasal reconstruction in 24
      patients. In one patient undergoing reconstruction of the nasal dorsum and in one
      undergoing reconstruction of the nasal tip, the texture of the forearm flap did
      not match well, which resulted in a slightly unsatisfactory aesthetic outcome. In
      one patient in whom the glabella, nasal dorsum, and part of the cheek were
      reconstructed simultaneously, a web was formed at the medial ocular angle, and a
      secondary operation was subsequently performed using Z-plasty. In one patient
      undergoing reconstruction with a forehead flap, defatting was required to reduce
      the bulk of the subcutaneous flap pedicle at the glabella. However, suture lines
      were placed in the most inconspicuous sites in all patients, and the use of a
      trapdoor contraction emphasized the three-dimensional appearance of the nose. The
      use of these aesthetic subunits for reconstruction offers several advantages,
      particularly in Oriental patients. Because the nasal dorsum is reconstructed
      together with the side walls, tenting of the nasal dorsum is avoided, which
      prevents a flat appearance of the nose. A forehead flap is useful in the repair
      of complex defects. Defects of the alae should be separately reconstructed with a
      nasolabial flap to enhance the effect of the trapdoor contraction and to
      highlight the three-dimensional appearance of the nose. Candidates for
      reconstruction should be selected on the basis of nasal structure. The results
      suggest that these units can also be used in some white patients.

PMID- 10883610
TI  - Double-paddle peroneal tissue transfer for oromandibular reconstruction.
AB  - The double-paddle peroneal tissue transfer is a useful technique for
      reconstructing the extensive and complex defect that results after ablative
      surgery for oral cancer. It can facilitate the design and inset of the skin
      paddle and avoid the need for a second free flap. The two skin paddles can be
      based on either two cutaneous perforators of the peroneal vessels or two branches
      of a single cutaneous perforator. The authors report their experience with double
      paddle peroneal tissue flaps (10 fasciocutaneous and five osteocutaneous) in 15
      patients. The largest double paddle used was (16 x 9) (15 x 6) cm, and the
      smallest one was (7 x 5.5) (4.5 x 4) cm. All flaps were used for both intraoral
      and extraoral defect reconstruction. There was one single skin paddle necrosis
      caused by erroneous manipulation of the flap 1 week after the operation; however,
      the skin paddle had survived completely before the manipulation. All other flaps
      survived completely, with a good to excellent appearance, and no patient had a
      significant gait disturbance after the operation.

PMID- 10883611
TI  - Radiation therapy after immediate breast reconstruction with implants.
AB  - The use of implants in immediate breast reconstruction is presently a common
      option. However, the practice should be evaluated in consideration of possible
      adjuvant therapies needed to control disease and to rule out negative
      interactions. This article discusses the effects of radiotherapy on breast
      implants with regard to the final cosmetic result. Six out of 124 cases of
      immediate breast reconstruction with implants were followed and evaluated in
      terms of capsular contracture and final aesthetic result after adjuvant
      radiotherapy and compared with the results of 118 patients who did not require
      irradiation. All of the patients who received irradiation demonstrated poor to
      fair results, with grade III to IV capsular contracture. Two patients received
      radiation therapy for local recurrences, which worsened their capsular
      contracture, emphasizing the deleterious effect of irradiation on breast
      implants. Statistical analysis of the results demonstrated a significant
      difference between the two groups in terms of capsular contracture and breast
      symmetry. In the selection of patient candidates for immediate breast
      reconstruction with implants, adjuvant radiation therapy must be considered as a
      contraindication, at least from an aesthetic point of view.

PMID- 10883612
TI  - New microsurgical breast reconstruction using free paraumbilical perforator
      adiposal flaps.
AB  - Pedicled transverse rectus abdominis musculocutaneous (TRAM) flaps have generally
      been used for bilateral breast losses. The major disadvantages of this method are
      the total or partial loss of the rectus abdominis muscles and various resulting
      postoperative complications, such as abdominal bulging and lumbar pain. With the
      recent development of perforator flaps and supermicrosurgery with anastomosis of
      0.5-mm caliber vessels, these serious complications can be overcome with a
      paraumbilical perforator adiposal flap, without sacrificing the rectus abdominis
      muscle. The breasts of a 57-year-old woman who had undergone a bilateral
      subcutaneous mastectomy, including silicone prostheses, were repaired
      simultaneously with this new method using free paraumbilical perforator adiposal
      flaps. This new method of breast augmentation with a vascularized adiposal flap
      and without any muscle component is minimally invasive; its advantages are the
      preservation of the rectus abdominis muscles and the short time elevation for the
      adiposal flap.

PMID- 10883613
TI  - Factors affecting outcome in free-tissue transfer in the elderly.
AB  - Free-tissue transfers have become the preferred surgical technique to treat
      complex reconstructive defects. Because these procedures typically require longer
      operative times and recovery periods, the applicability of free-flap
      reconstruction in the elderly continues to require ongoing review. The authors
      performed a retrospective analysis of 100 patients aged 65 years and older who
      underwent free-tissue transfers to determine preoperative and intraoperative
      predictors of surgical complications, medical complications, and reconstructive
      failures. The parameters studied included patient demographics, past medical
      history, American Society of Anesthesiology (ASA) status, site and cause of the
      defect, the free tissue transferred, operative time, and postoperative
      complications, including free-flap success or failure. The mean age of the
      patients was 72 years. A total of 46 patients underwent free-tissue transfer
      after head and neck ablation, 27 underwent lower extremity reconstruction in the
      setting of peripheral vascular disease, 10 had lower extremity traumatic wounds,
      nine had breast reconstructions, four had infected wounds, two had chronic
      wounds, and two underwent transfer for lower extremity tumor ablation. Two
      patients had an ASA status of 1, 49 patients had a status of 2, 45 patients had a
      status of 3, and four had a status of 4. A total of 104 flaps were transferred in
      these 100 patients. There were 49 radial forearm flaps, 34 rectus abdominis
      flaps, seven latissimus dorsi flaps, seven fibular osteocutaneous flaps, three
      omental flaps, three jejunal flaps, and one lateral arm flap. Four patients had
      planned double free flaps for their reconstruction. Mean operative time was 7.8
      hours (range, 3.5 to 16.5 hours). The overall flap success rate was 97 percent,
      and the overall reconstructive success rate was 92 percent. There were six
      additional reconstructive failures related to flap loss, all of which occurred
      more than 1 month after surgery. Patients with a higher ASA designation
      experienced more medical complications (p = 0.03) but not surgical complications.
      Increased operative time resulted in more surgical complications (p = 0.019). All
      eight cases of reconstructive failure occurred in patients undergoing limb
      salvage surgery in the setting of peripheral vascular disease. Free-tissue
      transfer in the elderly population demonstrates similar success rates to those of
      the general population. Age alone should not be considered a contraindication or
      an independent risk factor for free-tissue transfer. ASA status and length of
      operative time are significant predictors of postoperative medical and surgical
      morbidity. The higher rate of reconstructive failure in the elderly peripheral
      vascular disease population compares favorably with other treatment modalities
      for this disease process.

PMID- 10883614
TI  - Racial distribution of Dupuytren's disease in Department of Veterans Affairs
      patients.
AB  - Dupuytren's disease is a polyclonal fibroproliferative disorder of the palmar
      fascia of unclear pathogenesis. It has been described as a disease of northern
      European men and is reportedly rare in other races. A 10-year retrospective study
      using the Department of Veterans Affairs computer system was conducted to
      determine the racial distribution of this disorder among patients treated at all
      Department of Veterans Affairs medical centers. The study also determined
      demographic and clinical characteristics of black veterans treated for the
      condition at department medical centers. There were 9938 patients identified
      between the fiscal years of 1986 and 1995, of whom 412 were black (estimated
      prevalence of 130 per 100,000 population), 9071 were white (734 per 100,000), 234
      were Hispanic white (237 per 100,000), 11 were Native American (144 per 100,000),
      8 were Asian (67 per 100,000), and 202 were of unknown race. The characteristics
      of the disease in blacks are similar to those in whites. In both groups, the
      disease has a late onset, affects predominantly the ulnar digits, and is
      associated with other medical conditions, such as alcoholism, smoking, and
      diabetes. Unlike Dupuytren's disease in whites, however, the disease is rarely
      bilateral in blacks. The differential prevalence among racial groups suggests a
      genetic component to the pathogenesis of the disease.

PMID- 10883615
TI  - Rice cooker steam hand burn in the pediatric patient.
AB  - Burn injuries often lead to significant cosmetic and functional deformity. In the
      Orient, household electric rice cookers have caused a significant number of steam
      burns to infant hands. The clinical course and treatment outcome of these burns
      have been studied retrospectively in a review of the medical records of 79
      pediatric patients treated for acute hand steam burns and of 38 other patients
      who underwent correction for postburn contracture. Electric rice cookers caused
      all of the acute pediatric steam burns treated at our institute. Of the 81 hands
      treated between 1995 and 1998, 38.3 percent healed with conservative treatment
      and 61.7 percent required skin grafting. The volar aspects of the index and
      middle fingers were those most frequently involved. Eighteen of 36 hands (50
      percent) grafted with split-thickness skin developed late contractures requiring
      additional procedures. Among the 38 patients who underwent correction for
      postburn deformity, initial treatment was split-thickness grafting for 60.5
      percent, full-thickness skin grafting for 7.9 percent, and spontaneous healing
      for 31.6 percent. Awareness among medical personnel and continued public
      education should be promoted to help prevent this unique type of pediatric steam
      burn from occurring.

PMID- 10883616
TI  - Muscle-splitting approach to superior and inferior gluteal vessels: versatile
      source of recipient vessels for free-tissue transfer to sacral, gluteal, and
      ischial regions.
AB  - The superior gluteal vessel has been reported as a recipient in free-tissue
      transfer for the coverage of complex soft-tissue defects in the lumbosacral
      region, where a suitable recipient vessel is difficult to find. The
      characteristics of proximity, vessel caliber, and constancy make the superior
      gluteal vessel preferable to previously reported recipient vessels. However,
      there are technical difficulties in microsurgery (e.g., short pedicle length and
      deep location) and muscle injury (transection of the muscle) associated with use
      of the superior gluteal vessel. The purpose of this article is to present a
      modification of an approach to the gluteal vessel to alleviate technical
      difficulties and minimize muscle injury. From August of 1997 to January of 1999,
      six patients received microvascular transfer of the latissimus dorsi muscle or
      myocutaneous flap to the sacral (4) and ischial (2) regions. The causes of
      defects were tumor (1), trauma (1), and pressure sores (4). A muscle-splitting
      approach was used on the superior gluteal vessel and was later applied to the
      inferior gluteal vessel. The gluteus maximus muscle was split as needed in the
      direction of its fibers, and the perforators were dissected down to the superior
      or inferior gluteal artery and vein deep into the muscle. The follow-up period
      ranged from 6 to 22 months, and all of the flaps survived with complete recovery
      of the lesion. The major drawbacks of using the superior and inferior gluteal
      vessels can be overcome with the muscle-splitting approach, which provides
      increased accessibility and additional length to the vascular pedicle while
      causing minimal injury to the muscle itself. It also proves to be an easy, safe,
      and reliable method of dissection. When free-tissue transfer to sacral, gluteal,
      and ischial regions is indicated, the muscle-splitting approach to the superior
      and inferior gluteal vessels is a recommended option in the selection of a
      recipient vessel.

PMID- 10883617
TI  - Histologic change of arteriovenous malformations of the face and scalp after free
      flap transfer.
AB  - In three patients with long-standing vascular malformations of the face and
      scalp, radial forearm free flaps were transferred after a near-total excision of
      the lesion. All patients had typical high-flow malformations with thrill and
      bruit. The onset and progression of the malformations were analyzed through
      clinical and histologic studies. After free flap transfer, the vascular
      malformations were followed up grossly and histologically for between 4 and 9
      years. There was no recurrence of arteriovenous malformation after free flap
      transfer. The portion of the residual lesion adjacent to the transferred free
      flap disappeared, and the remaining discoloration also vanished grossly.
      Histologic comparison of immediate postoperative and 4-month postoperative
      specimens from the margin and residual lesion using Victoria blue staining showed
      that the typical preoperative findings for arteriovenous malformation-an
      intermingling of thick-walled vessels with abundant elastic fibers and thin
      walled vessels without elastic fibers-had undergone change, resulting in the
      disappearance of the thick-walled vessels and leaving only homogeneous, thin
      walled vasculature. The highly vascularized free flap, which does not contain
      abnormal fistulas, impacted the histologic change of the arteriovenous
      malformation by blocking the vicious cycle of ischemia and anatomic replacement
      of disfigured skin and subcutaneous tissues.

PMID- 10883618
TI  - Sideburn reconstruction with an arterial V-Y hair-bearing scalp flap after the
      excision of basal cell carcinoma.
AB  - A new flap is presented for sideburn reconstruction. It has good vascularity and
      hair direction. There is some tension in the closure of the scalp donor site that
      can be associated with alopecia. The flap should be advanced only to the desired
      sideburn level, with a cervicofacial flap covering any remaining defect. Follow
      up at 2 years 4 months confirmed the satisfactory result. This flap adds another
      option to those discussed in this article for sideburn reconstruction.

PMID- 10883619
TI  - Complete breast absence revisited.
AB  - Congenital absence of the breast is a rare condition. The literature shows that
      there is much heterogeneity in its presentation as well as its inheritance. We
      described a mother and daughter with the condition and how the mother underwent
      breast reconstruction with use of bilateral transverse rectus abdominis
      myocutaneous flaps.

PMID- 10883620
TI  - Late reconstruction of two total metacarpal bone defects using lengthening
      devices and a double-barrel osteocutaneous free parascapular flap.
AB  - A case was presented in which the late reconstruction of left ring and little
      metacarpal bone defects was carried out using a lengthening device and a double
      barrel osteocutaneous free parascapular flap. With this flap, up to 14 cm of
      nearly straight bone of a suitable width and length for the reconstruction of two
      metacarpal bones was raised safely. However, it required 3 months of lengthening
      to create enough space to insert the grafted bone because of the severe
      resistance of scar contracture and fibrous tissues.

PMID- 10883621
TI  - Use of the vascular closure staple clip applier for microvascular anastomosis in
      free-flap surgery.
AB  - We report our initial experience using the vascular closure staple clip applier
      (a nonpenetrating titanium clip applied in an interrupted, everting fashion) for
      microvascular anastomosis in free-flap surgery. In total, 153 anastomoses were
      performed in 87 free flaps (174 potential anastomoses) using the vascular closure
      stapler between October of 1997 and June of 1999. In 66 flaps, both the arterial
      and venous anastomosis were performed with the clip applier, whereas in 21 flaps
      only the venous anastomosis was performed using the clips. A total of 146
      anastomoses were performed in an end-to-end fashion, and seven were performed end
      to-side. Of the 87 flaps there were 53 TRAM flaps, seven bilateral TRAM, five
      latissimus dorsi, four gastrocnemius, three rectus abdominis, two radial forearm
      fibula, and four Rubens fat-pad flaps. Seventy flaps were used for breast
      reconstruction, seven flaps for lower limb reconstruction, four flaps for head
      and neck reconstruction, and six flaps for chest wall/trunk reconstruction. There
      were no postoperative anastomotic complications of bleeding, thrombosis, or need
      for revision (100 percent patency rate), with a significantly reduced time for
      completion of anastomoses. The clip applier is a safe, reliable method for
      performing microvascular anastomoses, allowing reduced operating time and
      possible cost savings in free-flap surgery.

PMID- 10883622
TI  - A simple method for forehead unit reconstruction.
AB  - The supratrochlear and supraorbital vessel-based island flap was used to avoid
      excessive scarring during reconstruction of the unilateral forehead defects after
      surgical excision of a malignant tumor. This method had a number of advantages:
      operation time was short, it was a one-stage procedure, the technique was
      relatively simple, a good match of the texture and color could be achieved, and
      scars were inconspicuous.

PMID- 10883623
TI  - Amputation of the middle ray in the primary treatment of severe injuries of the
      central hand.
AB  - Severe injury to the middle finger often compromises both the appearance and
      function of the hand. This report discusses the use of total middle ray
      amputation at the time of primary trauma surgery to avoid predictable problems
      that arise when the ray, or part of it, is retained. Primary ray amputation
      eliminates the defective middle finger, avoids a gap hand, and reunites the
      dissociated radial and ulnar segments of the hand to create a useful, three
      fingered hand.

PMID- 10883624
TI  - Converting to digital photography: a model for a large group or academic
      practice.
AB  - Digital photography has become an economical and efficient substitute for
      conventional photography. We recently converted our resident clinical photography
      to a digital format to make archiving more efficient and to save the costs of
      clinical photography. We present a model that can be applied to a large group or
      academic practice outlining the conversion of our clinical photography to digital
      format. We discuss the costs that we have incurred during the past 3 years of
      conventional photography, the economic benefit and costs for conversion to
      digital, and a 5-year projection of savings using digital photography. We also
      discuss the advantages of digital photography and the equipment needed for the
      conversion.

PMID- 10883625
TI  - Dupuytren's disease: an overview.

PMID- 10883626
TI  - Cosmetic surgery and patients who smoke: should we operate?

PMID- 10883627
TI  - Patient acceptance of adequately filled breast implants using the tilt test.
AB  - Adequate fill of any breast implant, regardless of shell characteristics, shape,
      or filler material, is important to prevent implant shell wrinkling, folding, or
      collapse that could potentially decrease the life of the implant. Implant shell
      life is a major factor that affects reoperation rates. The greater the necessity
      of reoperations, regardless of implant type, the greater the rate of local
      complications, necessitating additional surgery with additional risks and costs
      to patients. Palpable shell folding, visible wrinkling or rippling, palpable
      shifts of filler material, sloshing, and compromised aesthetic results can result
      from an under-filled implant. Any of these complications can necessitate
      reoperations with increased risks and costs to patients. This is a study of 609
      consecutive patients from January of 1993 to December of 1998 who were given
      detailed preoperative informed consent and a choice of implant shape and type and
      who chose the increased firmness associated with an implant that is adequately
      filled to pass the tilt test. This study addresses two questions: (1) Will
      patients accept the increased firmness of an implant that is filled to pass the
      tilt test? and (2) Is adequate fill by the tilt test useful clinically to help
      reduce the incidence of postoperative rippling, wrinkling, and spontaneous
      deflation in saline implants? Patients were followed by postoperative
      examinations and questionnaires. No patient requested implant replacement to a
      softer implant postoperatively, and no reoperations were performed for visible
      rippling or wrinkling. The spontaneous deflation rate over this 6-year period was
      9 of 1218 implants, or 0.739 percent. If patients will accept more firmness with
      an adequately filled implant, regardless of the filler material, surgeons might
      worry less about recommending an adequately filled implant to patients, and
      manufacturers might feel more comfortable producing adequately filled implants
      and redefining fill volumes for underfilled implants. More adequately filled
      implants could potentially reduce risks of reoperations by reducing premature
      shell failure and shell wrinkling complications.

PMID- 10883628
TI  - Hearing and ultrasound-assisted liposuction: the effect on surgeon and patient.
AB  - Ultrasound-assisted liposuction has become an important tool in body-contouring
      surgery. Although ultrasound frequency is by definition outside the range of
      normal human hearing, an audible sound is heard during ultrasound-assisted
      liposuction. This study measured sound intensity during ultrasound-assisted
      liposuction performed with two commercially available systems. Sound intensity
      was measured at the surgeon's ear, surgical site, and patient's glabella. All
      measurements obtained with both machines fell within acceptable standards as
      defined by the Occupational Safety and Health Administration. Use of ultrasound
      assisted liposuction does not pose a risk to the patient, the surgeon, or
      operating room personnel.

PMID- 10883629
TI  - Post-laser hypersensitivity and the atopic patient.
AB  - Laser resurfacing has become an extremely popular modality in the treatment of
      the aging face. Reported complications associated with carbon dioxide laser
      resurfacing are on the increase. One such complication involves the occurrence of
      significant hypersensitivity in laser and non-laser-treated areas, often
      occurring for weeks or months after the original treatment and necessitating
      topical or systemic steroid therapy. In an effort to identify patients at risk,
      those with significant hypersensitivity reactions were interviewed
      retrospectively. Questions regarding their background atopic characteristics were
      posed. Their responses to certain questions were then compared with those of a
      control group of 50 patients from the same pool who suffered no ill effects after
      laser therapy. A total of 151 patients were included in the study (pool). Of
      these, 14 patients (9.3 percent) suffered significant hypersensitivity. Detailed
      history in these patients revealed possible prior "allergic sensitivity" in 78.6
      percent of patients. In contrast, only 30 percent of 50 nonsymptomatic laser
      treated patients admitted to any positive allergic tendencies. It is likely that
      carbon dioxide laser resurfacing may trigger a sensitivity reaction in
      susceptible individuals.

PMID- 10883630
TI  - Segmental bone and cartilage reconstruction of major nasal dorsal defects.
AB  - This article describes the results of segmental bone and cartilage reconstruction
      of significant nasal dorsal defects. Solid bone graft reconstructions frequently
      lead to an unnatural hardness of the nasal tip. Rib cartilage reconstructions are
      pliable and soft but are a problem because they easily undergo warpage. The
      operation is performed using the open approach. Outer cranial bone graft is used
      for the bone component and extends at least two-thirds of the length of the
      dorsum. It is secured in place with a compression screw and a Kirschner wire. The
      cartilage component consists of an abbreviated L strut constructed of septal or
      conchal cartilage. It is slotted into the cranial bone in a tongue-in-groove
      manner and is sutured to it through a drill hole in the bone. The dorsal profile
      is completed with a single cartilage onlay graft or multiple sagittal cartilage
      grafts secured to the sides of the L strut. Twelve patients underwent segmental
      reconstruction of nasal deformities. Within this group, five patients underwent
      secondary rhinoplasty, five underwent posttraumatic rhinoplasty, and two
      underwent nose augmentation for Oriental features. There were seven men and five
      women. In all cases, good nasal tip mobility was maintained, and the nasal tips
      were soft. The interface between the bone graft and cartilage graftwas well
      camouflaged. The two did not separate. This procedure follows the principle of
      replacing lost tissue with like materials.

PMID- 10883631
TI  - Combined conchal cartilage-ethmoid bone grafts in nasal surgery.
AB  - Septal cartilage grafts are frequently required in rhinoplasties and nasal
      reconstructions. Unfortunately, sufficient septum is not always available for
      graft purposes. Conchal cartilage can serve as a substitute, but its usefulness
      is limited because of its soft, elastic nature. Applying thin sheets of pliable
      ethmoid bone to conchal cartilage gives the cartilage greater strength and, at
      the same time, allows it to retain some flexibility. This article examines the
      role of combined conchal cartilage-ethmoid bone grafts in nasal surgery. These
      grafts are simple to construct and are versatile in their application. By
      maintaining a free cartilage edge, they are readily sutured into place. The
      results seem to last long term.

PMID- 10883632
TI  - Mandibular matrix implant system: a method to restore skeletal support to the
      lower face.
AB  - Disharmony between the skeletal support and the softtissue envelope is a common
      cause of aesthetic concerns regarding the lower face. A loss of volume or a
      genetically small mandible affects the aesthetics and function of the mouth,
      chin, and neck. Because of the limitations of correcting such problems with
      current implants made of silicone or porous polyethylene, the author developed an
      implant system and a method of restoring the entire volume of the mandible called
      the mandibular matrix implant system. This implant system is made of high-density
      porous polyethylene and is composed of an articulated wraparound geniomandibular
      implant and a wraparound gonial angle implant. A prejowl implant can be
      integrated in the system as an addition or as a replacement for a chin implant.
      This implant system has different sizes and projections, and it can be modified
      by carving to fit the requirements of most patients. Carving is done using an
      appropriate sizer. This implant system is indicated for use in patients with a
      congenitally small mandible, edentulous patients, and patients requesting facial
      enhancement. The mandibular matrix implant system is implanted either during a
      single procedure or simultaneously with a facial rejuvenation. The extended
      geniomandibular implant is introduced through an anterior oral sulcus incision or
      a submental incision. The mandibular angle implant is introduced through a
      retromolar incision. The posterior end of the chin implant overlaps the anterior
      end of the gonial implant, and screw fixation of each chin component helps to
      stabilize the entire system. Antibiotics, irrigation, and closure of the
      incisions are performed before any additional operative procedure. The complete
      system has been used in 13 patients; one additional patient had the complete
      system plus an overlapping additional left prejowl implant for correction of
      asymmetry. Complications were manageable; these included one mandibular angle
      implant displacement and one infection. The implant displacement required a
      reoperation to reset the implant. The infection was treated with irrigation and
      closed system suction; the implant was salvaged. The satisfaction of patients has
      been high, and the author can now solve aesthetic problems that in the past were
      considered unsolvable.

PMID- 10883633
TI  - Dispelling the myths and misconceptions about transumbilical breast augmentation.
AB  - Since its invention in 1991, the transumbilical breast augmentation (TUBA)
      technique has gained popularity, and it has been proven safe and effective. In
      addition, the technique has several advantages over other methods of breast
      augmentation. Nevertheless, the method has often been the subject of a great
      variety of criticisms. Careful examination of those criticisms reveals that most
      are, in fact, untrue; they are misconceptions at best and falsehoods at worst. In
      this article, the author examines the 20 most common misconceptions about this
      procedure, clarifies or corrects them as appropriate, and suggests possible
      reasons for their having arisen in the first place. In addition, the actual
      drawbacks of the technique are reviewed. The author also outlines what he
      considers to be the criteria necessary for a surgeon to criticize any technique
      being used successfully by others: the surgeon must have proper plastic surgical
      training and certification, have completed training in the specific technique,
      and have a personal experience with performing a minimum number of cases.

PMID- 10883634
TI  - Effects of traditional and ultrasonic liposuction on adipose tissue: a
      biochemical approach.
AB  - Little is known about the interaction of ultrasonic liposculpture with fat
      tissue. The surgical technique is well established and its clinical effects are
      satisfactory. However, the in vivo effects on adipose tissue remain to be
      determined. Previous studies have shown that ultrasound waves break fat cells.
      The purpose of this study was to ascertain whether ultrasound waves can cause the
      release of fatty acids from the molecular structure of triglycerides. A double
      blind study was designed with samples obtained from traditional and ultrasonic
      liposuction of an equivalent area in the same patient. Samples were checked for
      triglycerides and for free fatty acids. Triglyceride values were always higher in
      the sample that had undergone ultrasonic procedure. No significant differences
      were observed between the free fatty acid chromatograms of the two kinds of
      samples analyzed. Data showed that no changes occurred in the triglyceride
      molecule when using ultrasound waves in the experimental conditions.

PMID- 10883635
TI  - The right angle rhytidectomy flap.
AB  - A detailed description of a simple technique to minimize scarring and hairline
      elevation following rhytidectomy is provided. The technique is illustrated with a
      step-by-step account of planning and performance.

PMID- 10883636
TI  - Toxic shock syndrome after suction lipectomy.
AB  - We present a case of toxic shock syndrome with necrotizing fasciitis after
      suction lipectomy. The patient underwent aesthetic suction lipectomy of the
      abdomen, buttocks, and thighs during an office procedure by a cosmetic surgeon.
      On postoperative day 2, the patient was referred to the emergency department of
      our hospital because of pain. On admission, the patient was in toxic shock. She
      required intensive medical treatment for about 1 month, along with psychiatric
      help to adapt after the illness. Although toxic shock syndrome is a rare
      postoperative complication, every plastic surgeon should be acquainted with it. A
      combination of early recognition, diagnosis, and aggressive supportive therapy is
      the only successful treatment.

PMID- 10883637
TI  - Distal, dorsal superior extremity plasty.
AB  - Multiple deep wrinkles and redundant skin over the dorsal hand, wrist, and
      forearm develop and become of cosmetic importance to some patients as they age.
      Distal, dorsal superior extremity plasty was performed in selected patients by
      excising redundant skin and wrinkles from the dorsal hands, wrists, and forearms.
      The area of skin to be excised is elliptical, with the long axis of the ellipse
      centered over the wrinkles on the dorsal wrist. The amount of skin to be excised
      (i.e., the short axis of the ellipse) is determined by grasping the dorsal wrist
      skin, hence advancing the dorsal forearm and hand skin, while the patient flexes
      the wrist. This maneuver is performed to avoid excessive excision of dorsal wrist
      skin, which would cause decreased wrist flexion. The surgical procedure is
      performed with use of magnification to avoid sensory nerve injury. A relatively
      large volume of lidocaine is injected subcutaneously to increase the distance
      between the skin and nerves and therefore decrease the risk of nerve injury. The
      skin edges are undermined for 1 to 1(1/2) cm, and the wound is closed in two
      layers. The wrist is splinted in 30 to 45 degrees of extension to decrease wound
      tension. The procedure produces long-lasting, good to excellent cosmetic
      improvement and patient satisfaction. The dorsal wrist, hand, and forearm appear
      smoother and more youthful, and scars are relatively inconspicuous. Potential
      significant complications include injury to the superficial branch of the radial
      nerve and dorsal branch of the ulnar nerve, wound dehiscence, and decreased range
      of motion of the wrist. Use of magnification, a bloodless field, injection of a
      relatively large volume of local anesthetic (10 to 12 cc), knowledge of regional
      anatomy, and careful surgical technique decrease the risk of nerve injury.
      Avoidance of injury to the superficial sensory branches of the radial and ulnar
      nerves is absolutely necessary for patient satisfaction. Avoidance of injury to
      the wound edges with good surgical technique, postoperative immobilization with
      the wrist in an extended position, and subsequent advancement of the wrist to a
      neutral position for several weeks decrease the risk of wound dehiscence.
      Avoidance of excessive skin excision and prolonged wrist immobilization lowers
      the risk of decreasing range of motion. There have been no complications in
      patients who underwent this procedure.

PMID- 10883638
TI  - A modest proposal.

PMID- 10883639
TI  - Tumescence: a valuable adjunct for the excision of facial hemangiomas.

PMID- 10883640
TI  - The Chiba University chronology for total ear reconstruction.

PMID- 10883641
TI  - A splint design for postoperative prominent ear retraction.

PMID- 10883642
TI  - Preparing liposuction patients at home preoperatively by scrub-showering.

PMID- 10883643
TI  - A practical method of sterile draping.

PMID- 10883644
TI  - Symptomatic macromastia in a patient with Poland syndrome.

PMID- 10883645
TI  - The angular branch of the thoracodorsal artery and its blood supply to the
      inferior angle of the scapula: an anatomical study.

PMID- 10883646
TI  - Botox and the management of pectoral spasm after subpectoral implant insertion.

PMID- 10883647
TI  - Silicone gel implant capsules and Chlamydia antigens.

PMID- 10883648
TI  - A method for developing individualized Wise keyhole patterns: an aid in reduction
      mammaplasty for asymmetric breast.

PMID- 10883649
TI  - Suction mammoplasty: the use of suction lipectomy to reduce large breasts.

PMID- 10883650
TI  - The role of sclerotherapy in abnormal varicose hand veins.

PMID- 10883651
TI  - Replantation of great and second toes: a worthwhile effort.

PMID- 10883652
TI  - Role of large superficial veins in distally based flaps of the extremities.

PMID- 10883653
TI  - Customizing bone anchors.

PMID- 10883654
TI  - Wooden skewers are cheap, effective, versatile, and safe instruments for the
      preoperative marking of skin incision lines.

PMID- 10883655
TI  - A new concept for the management of postburn contractures.

PMID- 10883656
TI  - Syllogism in plastic surgery.

PMID- 10883657
TI  - The Internet: a new friend to plastic surgeons.

PMID- 10883658
TI  - Differential expression of matrix metalloproteinases and their tissue-derived
      inhibitors in cutaneous wound repair--a correction.

PMID- 10883659
TI  - Recent advances in research on multistage tumorigenesis.
AB  - Tumour development is a multi-step process during which genetic and epigenetic
      events determine the transition from a normal to a malignant cellular state. In
      the past decade, extensive effort has been made not only to define the molecular
      mechanisms underlying progression to malignancy but also to predict the
      development of the disease and to identify possible molecular targets for
      therapy. Common to most tumours, several regulatory circuits are altered during
      multistage tumour progression, most importantly, the control of proliferation,
      the balance between cell survival and programmed cell death (apoptosis), the
      communication with neighbouring cells and the extracellular matrix, the induction
      of tumour neovascularization (angiogenesis) and, finally, tumour cell migration,
      invasion and metastatic dissemination. De-regulation of each of these processes
      represents a rate-limiting step for tumour development and, hence, has to be
      achieved by tumour cells in a highly selective manner during tumour progression.
      In this review we summarize recent advances in cancer research that have provided
      new insights in the molecular mechanisms underlying the transition between one
      tumour stage and the next and into their concerted action during tumour
      progression. Cultured human tumour cell lines as well as transgenic and knock-out
      mouse models of tumorigenesis have been instrumental in these experimental
      approaches.

PMID- 10883660
TI  - What can we learn from phase II adjuvant trials in melanoma?

PMID- 10883661
TI  - Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta
      analysis of randomized trials of a cisplatin-containing regimen versus a regimen
      without this alkylating agent.
AB  - Chemotherapy is the backbone of small-cell lung cancer therapy. However, optimal
      drug combinations and schedules remain to be defined and there is hitherto no
      world-wide accepted standard regimen. Cisplatin, an alkylating agent with high
      putative toxicity is currently widely used although its effectiveness in this
      disease has not been established firmly. We conducted a meta-analysis of
      published data reporting trials randomizing a cisplatin-containing regimen versus
      a regimen without this alkylating agent in order to determine possible
      differences in survival response and toxicity. Nineteen trials have been
      identified in medical literature (4054 evaluable patients). Ten trials randomized
      patients to receive a cisplatin-etoposide regimen versus a regimen without any of
      these two drugs. A subgroup analysis was, therefore, carried out in the nine
      remaining trials that randomly allocated patients between two regimens differing
      in the absence or presence of cisplatin, whereas etoposide was given (or not
      given) in both arms (1579 evaluable patients). The DerSimonian and Laird method
      was used to estimate the size effects and the Peto and Yusuf method was used in
      order to generate the odds ratios (OR) of reduction in risk of death and the
      increase in probability of being responders to chemotherapy. There was no
      significant difference between the cisplatin-containing regimen and the regimen
      without this drug when the risk of toxic-death was taken into account with
      respective probabilities of 3.1 and 2.7% (NS). Patients randomized in a cisplatin
      containing regimen had an increase in probability of being responders with an OR
      of 1.35, 95% confidence interval (CI) of 1.18-1.55; P < 10(-5) corresponding to
      an increase of objective (partial plus complete) response rate from 0.62 to 0.69
      (a result taking into account a significant heterogeneity). Patients treated with
      a cisplatin-containing regimen benefited from a significant reduction of risk of
      death at 6 months and 1 year with respective OR 0.87, 95% CI 0.75-0.98, P = 0.03,
      and or 0.80, 95% CI 0.69-0.93, P = 0.002 (no statistical heterogeneity). This
      corresponded to a significant increase in the probability of survival of 2.6% and
      4.4% at 6 months and 1 year respectively. The meta-analysis restricted to the
      subset of nine trials without etoposide treatment imbalance reached similar
      conclusions. A cisplatin-containing regimen yields a higher response rate and
      probability of survival than does a chemotherapy containing others alkylating
      agents without a perceptible increase in risk of toxic-death.

PMID- 10883662
TI  - The effect of tamoxifen and cisplatin on the disease-free and overall survival of
      patients with high risk malignant melanoma.
AB  - The adjuvant treatment of high-risk malignant melanoma remains problematic.
      Previously we reported moderate success in the treatment of metastatic disease
      using tamoxifen, cisplatin, dacarbazine and carmustine. Based upon data that
      suggested tamoxifen and cisplatin were the active agents in this regimen, we
      initiated a phase II trial of this combination in the adjuvant setting. We
      treated 153 patients with 4 cycles of tamoxifen (160 mg day(-1), days 1-7) and
      cisplatin (100 mg m(-2), day 2) for 28-day intervals. Patients received an anti
      nausea regimen of dexamethasone with ondansetron or granisetron. During the first
      2 years of follow-up, patients were evaluated every 2 months with a history,
      physical exam, laboratory work and computed tomography scans of the chest,
      abdomen and pelvis every 4 months. Thereafter, patients were evaluated every 3
      months and radiographic studies were performed if necessary. Currently, with a
      median follow-up of 36 months, the disease-free survival (DFS) is 68.4% and
      overall survival (OS) is 84.5%. Kaplan-Meier analysis predicts a 5-year DFS of
      62% with an OS of 79%. Relapses after 20 months have been rare. No effect of
      gender or number of positive lymph nodes was noted, however, stage of disease
      prior treatment was a factor. The major toxicity proved to be gastrointestinal in
      nature with nausea the most prevalent symptom. Minimal renal, haematologic and
      neurologic toxicity occurred. These preliminary results suggest that there is a
      positive impact of tamoxifen and cisplatin on both the DFS and OS of high-risk
      malignant melanoma patients. The 5-year projected DFS and OS compare favourably
      with those reported for the ECOG 1684 trial and warrant confirmation in a
      prospective randomized trial.

PMID- 10883663
TI  - A phase I and pharmacokinetic study of the combination of capecitabine and
      docetaxel in patients with advanced solid tumours.
AB  - Capecitabine and docetaxel are both active against a variety of solid tumours,
      while their toxicity profiles only partly overlap. This phase I study was
      performed to determine the maximum tolerated dose (MTD) and side-effects of the
      combination, and to establish whether there is any pharmacokinetic interaction
      between the two compounds. Thirty-three patients were treated with capecitabine
      administered orally twice daily on days 1-14, and docetaxel given as a 1 h
      intravenous infusion on day 1. Treatment was repeated every 3 weeks. The dose of
      capecitabine ranged from 825 to 1250 mg m(-2) twice a day and of docetaxel from
      75 to 100 mg m(-2). The dose-limiting toxicity (DLT) was asthenia grade 2-3 at a
      dose of 1000 mg m(-2) bid of capecitabine combined with docetaxel 100 mg m(-2).
      Neutropenia grade 3-4 was common (68% of courses), but complicated by fever in
      only 2.4% of courses. Other non-haematological toxicities were mild to moderate.
      There was no pharmacokinetic interaction between the two drugs. Tumour responses
      included two complete responses and three partial responses. Capecitabine 825 mg
      m(-2) twice a day plus docetaxel 100 mg m(-2) was tolerable, as was capecitabine
      1250 mg m(-2) twice a day plus docetaxel 75 mg m(-2).

PMID- 10883664
TI  - Aberrant expression of cyclin A in head and neck cancer.
AB  - Cyclin A expression was studied in a series of 65 squamous cell carcinomas of the
      head and neck (HNSCC) and compared with known markers of proliferation,
      iododeoxyuridine (IdUrd) and Ki-67, to assess whether aberrant expression was
      prevalent. Patients had previously been administered IdUrd to study cell kinetics
      in relation to outcome of radiotherapy. The data showed that all three parameters
      were highly correlated although the absolute values were different. The median
      labelling indices (LI) for IdUrd, cyclin A and Ki-67 were 10.7, 17.1 and 30.8%
      respectively, reflecting the known pattern of differential cell cycle expression.
      However, there were a significant number of cases in which an unexpected
      relationship between cyclin A and either IdUrd or Ki-67 was present. Some of
      these were attributable to overexpression but others indicated underexpression.
      Although the greater variability and range of cyclin A expression, coupled with
      its more closely associated role in cell cycle regulation, might suggest that it
      may be a more informative marker for cell proliferation than Ki-67, the aberrant
      expression seen in over one third of cases would indicate that caution should be
      exercised in interpreting cyclin A as a surrogate marker of proliferation in
      HNSCC.

PMID- 10883665
TI  - Epithelial cells in bone marrow of oesophageal cancer patients: a significant
      prognostic factor in multivariate analysis.
AB  - The detection of epithelial cells in bone marrow, blood or lymph nodes indicates
      a disseminatory potential of solid tumours. 225 patients with squamous cell
      carcinoma of the oesophagus were prospectively studied. Prior to any therapy,
      cytokeratin-positive (CK) cells in bone marrow were immunocytochemically detected
      in 75 patients with the monoclonal anti-epithelial-cell antibody A45-B/B3 and
      correlated with established histopathologic and patient-specific prognosis
      factors. The prognosis factors were assessed by multivariate analysis. Twenty
      nine of 75 (38.7%) patients with oesophageal cancer showed CK-positive cells in
      bone marrow. The analyses of the mean and median overall survival time showed a
      significant difference between patients with and without epithelial cells in bone
      marrow (P < 0.001). Multivariate analysis in the total patient population and in
      patients with curative resection of the primary tumour confirmed the curative
      resection rate and the bone marrow status as the strongest independent prognostic
      factors, besides the T-category. The detection of epithelial cells in bone marrow
      of oesophageal cancer patients is a substantial prognostic factor proved by
      multivariate analysis and is helpful for exact preoperative staging, as well as
      monitoring of neoadjuvant therapy.

PMID- 10883666
TI  - Fluorescence in situ hybridization techniques for the rapid detection of genetic
      prognostic factors in neuroblastoma. United Kingdom Children's Cancer Study
      Group.
AB  - Neuroblastoma is the commonest extracranial solid tumour in children. There are a
      number of molecular genetic features known which are of prognostic importance and
      which are used to direct therapy. Identification and targeting of high-risk
      individuals with intensive therapeutic regimens may allow an improvement in
      survival rates. The most powerful biological parameters associated with prognosis
      in this malignancy are chromosomal changes, especially MYCN amplification,
      deletion of chromosome 1p and aneuploidy. Rapid characterization of these
      aberrations at the time of diagnosis is paramount if stratification according to
      risk group is to be achieved. This paper describes the rapid detection of
      del(1p), MYCN amplification and trisomy using interphase fluorescence in situ
      hybridization on imprints from fresh tumour biopsies. The results are related to
      those obtained by standard molecular methods and karyotyping.

PMID- 10883667
TI  - Reduced p21(WAF1/CIP1) protein expression is predominantly related to altered p53
      in hepatocellular carcinomas.
AB  - To investigate the relationship between the expression of p21(WAF1/CIP1) protein
      and p53 status and the possible role of the two proteins in hepatocellular
      carcinomas (HCCs), we examined the expression of p21(WAF1/CIP1) and p53
      immunohistochemically in 81 tumours from 65 patients with hepatocellular
      carcinoma. p21(WAF1/CIP1) protein was absent from 59 of 81 tumours (72.8%), and
      altered p53 expression was found in 43 (53.1%). p21(WAF1/CIP1) expression was
      significantly associated with p53 status (P = 0.0008); 38 of 59 tumours lacking
      p21(WAF1/CIP1) protein were accompanied by altered p53 expression. Further
      analyses showed that p21(WAF1/CIP1) expression was inversely correlated with p53
      expression in hepatitis C virus (HCV)-related HCCs, but not in HBV-related
      hepatocellular carcinomas and hepatocellular carcinomas without viral infection.
      All 11 tumours with intrahepatic metastasis showed altered p21(WAF1/CIP1) or p53
      expression. In contrast, no intrahepatic metastasis was found in any of the 17
      tumours without abnormal expression of either of the two proteins. These results
      suggest that: (1) different modes of p21(WAF1/CIP1) regulation are involved in
      HCCs differing in their hepatitis viral infection status, and p21(WAF1/CIP1)
      expression appears to be predominantly related to altered p53 in HCV-related
      HCCs; (2) disruption of the p53-p21(WAF1/CIP1) cell-cycle-regulating pathway may
      contribute to malignant progression of HCC.

PMID- 10883668
TI  - Effect of a fluorinated pyrimidine on cachexia and tumour growth in murine
      cachexia models: relationship with a proteolysis inducing factor.
AB  - The fluorinated pyrimidine nucleoside, 5'-deoxy-5-fluorouridine (5'-dFUrd) has
      been shown to effectively attenuate the progress of cachexia in the murine
      adenocarcinomas MAC16 and colon 26 as well as in the human uterine cervical
      carcinoma xenograft, Yumoto. Although concomitant inhibition of tumour growth was
      observed in all three models this was not sufficient to account for the
      preservation of body weight. An attempt has been made to correlate the anti
      cachectic activity of 5'-dFUrd with the presence of a tumour produced proteolysis
      inducing factor (PIF), thought to be responsible for the development of cachexia
      in the MAC16 model. Two variants of colon 26 adenocarcinoma were employed, clone
      20 which produces profound cachexia, and clone 5 which produces no change in body
      weight in recipient animals. Mice bearing the colon 26, clone 20 variant showed
      evidence for the presence of PIF in tumour, serum and urine, while there was no
      evidence for the presence of PIF in tumour or body fluids of mice bearing the
      clone 5 tumours. Treatment of animals bearing the clone 20 variant with 5'-dF Urd
      led to the disappearance of PIF from the tumour, serum and urine concomitant with
      the attenuation of the development of cachexia. The human cervical carcinoma,
      Yumoto, which also induced cachexia in recipiant animals, showed expression of
      PIF in tumour, serum and urine in control and vehicle-treated mice, but was
      absent in mice treated with 5'-dFUrd. Thus in these experimental models cachexia
      appears to be correlated with the presence of PIF.

PMID- 10883669
TI  - The 121 amino acid isoform of vascular endothelial growth factor is more strongly
      tumorigenic than other splice variants in vivo.
AB  - Vascular endothelial growth factor (VEGF) is known to occur as at least six
      differentially spliced variants, giving rise to mature isoforms containing 121,
      145, 165, 183, 189 and 206 amino acids. However, little is yet known concerning
      the in vivo activities of this differential splicing. Stably transfected MCF-7
      breast carcinoma cells were constructed that secreted comparable amounts of the
      121, 165 or 189 isoforms. Rabbit corneal angiogenesis assays showed the VEGF121
      transfectant to have much greater angiogenic activity than the 165 or 189
      expressing MCF-7 cells. While the VEGF121-expressing MCF-7 cells were
      reproducibly more tumorigenic than the control transfectants, this was not the
      case with the VEGF165- or VEGF189-expressing cells. More surprising was the
      observation that VEGF189 located to the nucleus, consistent with the presence of
      a highly conserved nuclear localization sequence in exon 6a that is expressed in
      VEGF189 but not 121 or 165. It was concluded that the VEGF121 isoform is both
      more angiogenic and tumorigenic than are the 165 and 189 isoforms. This is
      probably due to the ability of the 121 isoform, unlike the 165 and 189 isoforms,
      to freely diffuse from the cells producing it.

PMID- 10883670
TI  - Fern spore extracts can damage DNA.
AB  - The carcinogenicity of the vegetative tissues of bracken fern (Pteridium) has
      long been established. More recently, the carcinogenic effects of the spores of
      bracken have also been recognized. Both vegetative tissues and spores of bracken
      can induce adducts in DNA in animal tissues, but the possible genotoxic or
      carcinogenic effects of spores from fern species other than bracken are unknown.
      The single-cell gel electrophoresis ('comet') assay was used to investigate
      whether fern spores can cause DNA damage in vitro. Extracts of spores from six
      fern species were administered to cultured human premyeloid leukaemia (K562)
      cells. Spore extracts of five fern species: Anemia phyllitidis, Dicksonia
      antarctica, Pteridium aquilinum, Pteris vittata and Sadleria pallida, induced
      significantly more DNA strand breaks than those in the control groups. Only in
      one species, Osmunda regalis, was the effect no different from that in the
      control groups. Using extracts from A. phyllitidis and P. vittata, the extent of
      DNA damage was increased by increasing the original dose 10 times, whereas an
      experiment in which exposure times were varied suggested that the highest levels
      of strand breaks appear after 2 h exposure. Simultaneous incubation with human S9
      liver enzyme mix ablated the damaging effect of the extracts. Our data show that
      fern spore extracts can cause DNA damage in human cells in vitro. Considering the
      strong correlation between DNA damage and carcinogenic events, the observations
      made in this report may well have some implications for human health.

PMID- 10883671
TI  - Anti-tumour effects and pharmacokinetic profile of 17-(5'-isoxazolyl)androsta
      4,16-dien-3-one (L-39) in mice: an inhibitor of androgen synthesis.
AB  - 17-(5'-Isoxazolyl)androsta-4,16-dien-3-one (L-39), a novel androstene derivative,
      was synthesized and evaluated in vitro and in vivo. L-39 showed potent and non
      competitive inhibition of human testicular microsomal 17alpha
      hydroxylase/C(17,20)-lyase with an IC50 value of 59 nM and Ki of 22 nM. L-39 also
      showed potent and competitive inhibition of 5alpha-reductase in human prostatic
      microsomes with IC50 and Ki values of 33 and 28 nM respectively. L-39 (5 microM)
      has also been shown to manifest anti-androgenic activity in cultures of human
      prostate cancer cell lines (LNCaP) by preventing the labelled synthetic androgen
      R1881 (5 nM) from binding to the androgen receptors. Androgen-dependent human
      prostate cancer xenografts (PC-82) were grown in nude mice and the effects of L
      39 (50 mg kg(-1) day(-1)) on tumour growth and prostate-specific antigen (PSA)
      levels were determined after 28 days. L-39 significantly (P < 0.01) diminished
      tumour growth and wet weights to a similar extent as castration or flutamide
      treatment. L-39 also significantly (P < 0.01) reduced serum PSA levels by more
      than 80% in the mice bearing human prostate cancer xenografts. Pharmacokinetic
      studies were also conducted in male Balb/c mice. After subcutaneous
      administration of a single bolus dose, L-39 was rapidly absorbed into the
      systemic circulation. Peak plasma levels occurred at 0.75 h and then declined
      with a t(1/2) of 1.51 h. The bioavailability of L-39 after subcutaneous
      administration was 28.5%. These results demonstrate that L-39 is a potent
      inhibitor of androgen synthesis and is effective in reducing the growth of human
      prostate cancer xenografts in nude mice. Although improvements in the
      bioavailability are necessary, L-39 is a potential lead compound with this
      profile as an inhibitor of prostate cancer growth.

PMID- 10883672
TI  - Modulation of paclitaxel resistance by annexin IV in human cancer cell lines.
AB  - A recurring problem with cancer therapies is the development of drug resistance.
      While investigating the protein profile of cells resistant to a novel antimitotic
      compound (A204197), we discovered an increase in annexin IV expression. When we
      examined the annexin IV protein expression level in a paclitaxel-resistant cell
      line (H460/T800), we found that annexin IV was also overexpressed. Interestingly
      a closely related protein, annexin II, was not overexpressed in H460/T800 cells.
      Immunostaining with either annexin II or IV antibody revealed that annexin IV was
      primarily located in the nucleus of paclitaxel-resistant H460/T800 cells. Short
      term treatment of H460 cells with 10 nM paclitaxel for up to 4 days resulted in
      induction of annexin IV, but not annexin II expression. In addition, there was an
      increase in annexin IV staining in the nucleus starting at day 1. Furthermore,
      cells pretreated with 10 nM paclitaxel for 4 days resulted in cells becoming
      approximately fivefold more resistant to paclitaxel. Transfection of annexin IV
      cDNA into 293T cells revealed that there was a threefold increase in paclitaxel
      resistance. Thus our results indicate that annexin IV plays a role in paclitaxel
      resistance in this cell line and it is among one of the earliest proteins that is
      induced in cells in response to cytotoxic stress such as antimitotic drug
      treatment.

PMID- 10883673
TI  - Anal carcinoma in inflammatory bowel disease.
AB  - We followed 9602 patients with Crohn's disease or ulcerative colitis for anal
      squamous cell carcinoma for up to 18 years. No significant increase was observed:
      two cases occurred vs 1.3 expected during 99,229 person-years of observation,
      (standardized incidence ratio = 1.6; 95 confidence interval: 0.2-5.7). Anal
      squamous cell carcinoma is rare even in inflammatory bowel disease.

PMID- 10883675
TI  - Hormones and diet: low insulin-like growth factor-I but normal bioavailable
      androgens in vegan men.
AB  - Mean serum insulin-like growth factor-I was 9% lower in 233 vegan men than in 226
      meat-eaters and 237 vegetarians (P = 0.002). Vegans had higher testosterone
      levels than vegetarians and meat-eaters, but this was offset by higher sex
      hormone binding globulin, and there were no differences between diet groups in
      free testosterone, androstanediol glucuronide or luteinizing hormone.

PMID- 10883674
TI  - Secondary myelodysplastic syndrome/acute myeloid leukaemia following mitoxantrone
      based therapy for breast carcinoma.
AB  - Of 1774 patients with breast cancer given mitoxantrone (MTZ) with methotrexate (n
      = 492) or with methotrexate and mitomycin C (n = 1282), nine developed MDS/AML
      after a median of 2.5 years. Median duration of survival from diagnosis of
      MDS/AML was 10 months and six patients died. The crude incidence of developing
      MDS/AML after MMM or MM chemotherapy was 15 per 100,000 patient years follow-up,
      while the actuarial risk was 1.1% and 1.6% at 5 and 10 years respectively. MTZ
      based regimens carry a 10 x higher risk of subsequent MDS/AML compared to that
      seen in the general population.

PMID- 10883676
TI  - Identification of long-term survivors in primary breast cancer by dynamic
      modelling of tumour response.
AB  - Although clinical response to primary chemotherapy in stage II and III breast
      cancer is associated with a survival advantage, it is the degree of pathological
      response in the breast and ipsilateral axilla that best identifies patients with
      a good long-term outcome. A mathematical model of the initial response of 39
      locally advanced tumours to anthracycline-based primary chemotherapy has been
      previously shown to predict subsequent clinical tumour size. This model allows
      for the possibility of primary resistant disease, the presence of which should
      therefore be associated with a worse outcome. This study reports the application
      of this model to an additional five patients with locally advanced breast cancer,
      as well as to 63 patients with operable breast cancer, and confirms the
      biological reality of the model parameters for these 100 breast cancers treated
      with primary anthracycline-based chemotherapy. The tumours that responded to
      chemotherapy had higher cell-kill (P < 0.0005), lower resistance (P < 0.0001) and
      slower tumour regrowth (P < 0.002). Furthermore, ER-negative tumours had higher
      cell-kill (P < 0.05), as compared with ER-positive tumours. All patients with a
      pathological complete response had zero resistance according to the model.
      Furthermore, the long-term implication of chemo-resistant disease was
      demonstrated by survival analysis of these two groups of patients. At a median
      follow-up of 3.7 years, there was a statistically significantly worse survival
      for the 37 patients with locally advanced breast cancer identified by the model
      to have more than 8% primary resistant tumour (P < 0.003). The specificity of
      this putative prognostic indicator was confirmed in the 63 patients presenting
      with operable disease where, at a median follow-up of 7.7 years, those women with
      a resistant fraction of greater than 8% had a significantly worse survival (P <
      0.05). Application of this model to patients treated with neoadjuvant
      chemotherapy may allow earlier identification of clinically significant
      resistance and permit intervention with alternative non-cross-resistant therapies
      such as taxoids.

PMID- 10883677
TI  - Multicentric study on malignant pleural mesothelioma and non-occupational
      exposure to asbestos.
AB  - Insufficient evidence exists on the risk of pleural mesothelioma from non
      occupational exposure to asbestos. A population-based case-control study was
      carried out in six areas from Italy, Spain and Switzerland. Information was
      collected for 215 new histologically confirmed cases and 448 controls. A panel of
      industrial hygienists assessed asbestos exposure separately for occupational,
      domestic and environmental sources. Classification of domestic and environmental
      exposure was based on a complete residential history, presence and use of
      asbestos at home, asbestos industrial activities in the surrounding area, and
      their distance from the dwelling. In 53 cases and 232 controls without evidence
      of occupational exposure to asbestos, moderate or high probability of domestic
      exposure was associated with an increased risk adjusted by age and sex: odds
      ratio (OR) 4.81, 95% confidence interval (CI) 1.8-13.1. This corresponds to three
      situations: cleaning asbestos-contaminated clothes, handling asbestos material
      and presence of asbestos material susceptible to damage. The estimated OR for
      high probability of environmental exposure (living within 2000 m of asbestos
      mines, asbestos cement plants, asbestos textiles, shipyards, or brakes factories)
      was 11.5 (95% CI 3.5-38.2). Living between 2000 and 5000 m from asbestos
      industries or within 500 m of industries using asbestos could also be associated
      with an increased risk. A dose-response pattern appeared with intensity of both
      sources of exposure. It is suggested that low-dose exposure to asbestos at home
      or in the general environment carries a measurable risk of malignant pleural
      mesothelioma.

PMID- 10883678
TI  - Nested case-control study of the effects of non-steroidal anti-inflammatory drugs
      on breast cancer risk and stage.
AB  - We carried out a nested case-control study to measure the rate ratio (RR) for
      invasive female breast cancer in relation to non-steroidal anti-inflammatory drug
      (NSAID) use. The source population consisted of the female beneficiaries of the
      Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer
      since 1970. Four controls/case, matched on age and sampling time, were randomly
      selected. Dispensing rates during successive time periods characterized NSAID
      exposure. RRs associated with exposure during each period were adjusted for
      exposure during the others. Confounding by other determinants was studied in
      analyses adjusted with data obtained by interviewing samples of subjects accrued
      from mid-1991 to mid-1995. We accrued 5882 cases and 23,517 controls. Increasing
      NSAID exposure 2-5 years preceding diagnosis was associated with a trend towards
      a decreasing RR (P-trend = 0.003); for the highest exposure level RR = 0.76, 95%
      confidence interval 0.63-0.92. This protective effect could not be attributed to
      confounding by other determinants. In analyses involving only the cases, NSAID
      exposure 2-5 and 6-10 years preceding diagnosis was associated with significantly
      reduced risks of presenting with a large tumour (> 5 cm diameter) or distant
      metastasis, but not regional lymph node metastasis. The use of NSAIDs may retard
      the growth of breast cancers and prevent distant metastasis.

PMID- 10883679
TI  - High risk mammographic parenchymal patterns and diet: a case-control study.
AB  - Mammographic parenchymal patterns are related to breast cancer risk and are also
      thought to be affected by diet. We designed a case-control study comprising 200
      cases with high-risk (P2 and DY) mammographic parenchymal pattern and 200
      controls with low-risk (N1 and P1) patterns in order to investigate the effect of
      food and nutrient intake on mammographic patterns. Mammograms were evaluated
      according to the Wolfe classification system. Dietary data were obtained from 7
      day food diaries. Mean daily intake of nutrients was computed from standard UK
      food tables. The adjusted odds ratio (OR) of having a high-risk pattern in women
      in the highest tertile of total protein and carbohydrate intake was twice that of
      women in the lowest tertile (OR = 2.00; 95% confidence interval (CI) 1.06-3.77; P
      = 0.04 and OR = 1.93; 95% CI 1.03-3.59; P = 0.04 respectively). There was no
      excess risk for fat intake. In addition, there was no association between intake
      of vitamins and mammographic parenchymal patterns. Total meat intake was strongly
      and positively associated with high-risk patterns among post-menopausal women (OR
      = 2.50, 95% CI 1.09-5.69, P = 0.03). Our study suggests that certain
      macronutrients and foods such as protein, carbohydrate and meat intake influence
      the risk of breast cancer through their effects on breast tissue morphology,
      whereas fat and vitamins do not affect mammographic density. It seems that
      parenchymal pattern acts as an informative biomarker of the effect of some
      macronutrient and foodstuffs intake on breast cancer risk.

PMID- 10883680
TI  - A case-control study of oesophageal adenocarcinoma in women: a preventable
      disease.
AB  - The incidence of adenocarcinoma of the oesophagus in British women is among the
      highest in the world. To investigate its aetiology, we conducted a multi-centre,
      population based case-control study in four regions in England and Scotland. We
      included 74 incident cases in women with histologically confirmed diagnoses of
      adenocarcinoma of the oesophagus, and 74 female controls matched by age and
      general practice. High body mass index (BMI) around the age of 20 years (highest
      vs lowest quartile, adjusted odds ratio (OR) = 6.04, 95% confidence interval (CI)
      1.28-28.52) and low consumption of fruit (highest vs lowest quartile, adjusted OR
      = 0.08, 95% CI 0.01-0.49) were associated with increases in risk. Breastfeeding
      by women was associated with reduced risk of their subsequently developing this
      cancer (ever vs never, adjusted OR = 0.41, 95% CI 0.20-0.82) and there was a
      significant dose-response effect with total duration of breastfeeding. The
      summary population attributable risk from these three factors was 96% (90% if
      breastfeeding is excluded). We conclude that high BMI in early adulthood and low
      consumption of fruit are important risk factors for adenocarcinoma of the
      oesophagus. Breastfeeding may confer a protective effect but this needs
      confirmation. This cancer is a largely preventable disease in women.

PMID- 10883681
TI  - Reproductive factors are crucial in the aetiology of breast cancer.

PMID- 10883682
TI  - The Association of Cancer Physicians Breast Cancer Forum: implications of Calman
      Hine for breast cancer services.

PMID- 10883683
TI  - No time for hand-me-downs.

PMID- 10883684
TI  - The relationship between facial fractures and death from neurologic injury.
AB  - PURPOSE: The purpose of this study was to review patients who failed to survive
      blunt trauma and to determine whether there is a relationship between specific
      facial fracture patterns and death. PATIENTS AND METHODS: This was a
      retrospective record review of patients with facial fractures admitted to a level
      I trauma center between January 1, 1993 and December 31, 1996. Records were
      reviewed for gender, age, injury severity score (ISS), Glasgow Coma Scale (GCS),
      revised probability of survival (RPS), cause of death, and facial fracture
      pattern. Facial fracture patterns were grouped as lower face (mandible), midface
      (maxilla, zygoma, nose, and orbits), and upper face (frontal bone). Causes of
      death were grouped into neurologic, visceral, combined neurologic and visceral,
      and other. Surviving and nonsurviving groups were compared. Parametric data were
      analyzed with a pooled or separate variance t-test, nonparametric data with a
      Mann-Whitney U-test, and categorical variables with a chi-square test (P < or =
      .05). The odds ratio with corresponding 95% confidence intervals was used to show
      the association between facial fracture patterns and death. RESULTS: During the 4
      year period, 6,117 patients were admitted with blunt trauma, 661 (11%) of whom
      had facial fractures. Those who died were more likely to be older than those who
      survived, with a lower GCS, lower RPS, and higher ISS. Although there was a male
      predominance in the patient population, there was no gender difference between
      those who died and those who survived. Surviving patients were more likely to
      have only isolated mandible injuries. Nonsurvivors were more likely to have
      isolated midface fractures or combinations of midface and other facial fractures.
      The odds ratio showed a 13 to 75 times greater risk of patients dying of
      neurologic injury with patterns other than isolated mandible injury than with any
      mid- or upper-facial fracture patterns. CONCLUSIONS: Compared with survivors,
      nonsurviving patients with facial fractures were older and had a lower GCS,
      higher ISS, and lower RPS. Nonsurviving patients had a dramatic predilection for
      mid- and upper-facial fracture patterns and death of neurologic injury.

PMID- 10883685
TI  - Repair of the inferior alveolar nerve with a forearm cutaneous nerve graft after
      ablative surgery of the mandible.
AB  - PURPOSE: A method of autologous nerve grafting for repair of the inferior
      alveolar nerve after mandibular resection using a forearm cutaneous nerve is
      described. PATIENTS AND METHODS: The lateral cutaneous nerve of forearm served as
      the donor nerve, and the graft was inserted microsurgically using an epineurial
      nerve suture technique in 6 subjects. Return of sensation in these 6 patients was
      measured by the use of Semmes-Weinstein method. RESULTS: Sensibility of the lower
      lip and chin recovered after about 10 months in all 6 subjects. CONCLUSION: The
      lateral branch of the forearm cutaneous nerve is a useful graft for repair of the
      inferior alveolar nerve after mandibular resection in which a forearm flap is
      used as part of the reconstruction.

PMID- 10883686
TI  - Facial symmetry after closed and open treatment of fractures of the mandibular
      condylar process.
AB  - PURPOSE: This study compares vertical measures of mandibular and facial
      morphology after open or closed treatment for fractures of the mandibular
      condylar process. PATIENTS AND METHODS: One hundred forty-six patients (121 male,
      25 female), 81 treated by closed and 65 by open methods, were included in this
      study. Towne's and panoramic radiographs, taken at several intervals, were used
      to quantify the displacement of the condylar process fractures. Posteroanterior
      cephalograms taken at 6 weeks, 6 months, 1 year, and 2 to 3 years after treatment
      were used to assess posterior facial height and bigonial and occlusal plane
      angles. Additionally, panoramic radiographs were used to assess ramus height at
      the same periods. Standard statistical methods were used to assess differences
      between groups. RESULTS: Patients whose condylar process fractures were treated
      by closed methods had significantly shorter posterior facial and ramus heights on
      the side of injury, and more tilting of the occlusal and bigonial planes toward
      the fractured side, than patients whose fractures were treated by open methods.
      Most of the asymmetry in patients treated by closed methods was present by 6
      weeks after injury. CONCLUSIONS: Patients treated by closed methods develop
      asymmetries characterized by shortening of the face on the side of injury. It is
      likely that loss of posterior facial height on the side of fracture in these
      patients is an adaptation that helps reestablish a new temporomandibular
      articulation.

PMID- 10883687
TI  - Factors influencing the long-term outcome of mandibular reconstruction.
AB  - PURPOSE: The aim of this study was to understand the association of 30 candidate
      variables with the outcome of mandibular reconstruction. PATIENTS AND METHODS:
      Seventy cases of mandibular reconstruction performed between 1976 and 1991 were
      identified. Medical records were reviewed for all patients. Thirty variables,
      including patient factors, preoperative preparation, and intraoperative and
      postoperative findings were determined for each patient. Bone graft outcome was
      evaluated in 2 ways: 1) Fisher's exact tests and logistic regression models were
      used to determine the association between the clinical parameters and the success
      of the bone graft at 1 year and 2) proportional hazard regression models were
      then used to identify the predictors of bone graft survival time from the 30
      chosen variables. RESULTS: Multivariate analysis determined that greater blood
      loss during the procedure (P = .018) and the presence of postoperative recipient
      site complications (P = .010) were significantly associated with bone graft
      failure during the first year. The diagnosis of malignant disease (P = .006), the
      use of sternocleidomastoid muscle (SCM) flaps for soft tissue augmentation (P <
      .001), longer duration of suction drainage (P = .001), and the presence of
      postoperative recipient site complications (P = .013) were found to be
      significant predictors of graft survival time in the proportional hazard
      regression model. CONCLUSIONS: The analysis of parameters associated with bone
      graft outcome may aid in surgical decision making and help improve the likelihood
      of a successful result in the future.

PMID- 10883688
TI  - Long-term magnetic resonance imaging after temporomandibular joint discectomy
      without replacement.
AB  - PURPOSE: The intracapsular changes in patients who underwent discectomy without
      disc replacement were evaluated by magnetic resonance imaging (MRI) to determine
      the long-term outcome of this procedure. PATIENTS AND METHODS: Thirty-three
      patients observed for an average of 9 years 4 months (5 to 24 years) and 10
      asymptomatic volunteers underwent MRI using T1- and T2-weighted images and 3
      dimensional fast imaging with a steady precession sequence (FISP-3D) technique.
      The intracapsular changes, especially those in the joint space, were compared
      with the postoperative clinical findings. RESULTS: MRI examination of the
      temporomandibular joint in the 33 patients (35 joints) indicated the presence of
      tissue with an intermediate or high signal intensity in the joint space. This
      tissue covered the articular surface of the condyle and fossa. Thirty-two joints
      had no pain or only occasional, mild pain (3 joints). No patient had severe joint
      pain or a low signal intensity in the joint space on MRI examination. There was
      no correlation between joint noise and the presence of a tissue deformity in the
      joint space. MRI of 2 patients with limited mouth opening showed tissue with high
      signal intensity in the joint space as well as an exostosis on the eminence and
      hypertrophy of the condyle. CONCLUSION: Long-term success is possible with
      discectomy without replacement. This appears to be attributable to the formation
      of new tissue between the condyle and fossa that acts as a pseudodisc.

PMID- 10883689
TI  - Nonunion of the mandible: an analysis of contributing factors.
AB  - PURPOSE: The aim of this study was to review our experience of nonunion of
      mandible fractures and to compare this information with the past and present
      literature. The analysis also evaluated risk factors and those conditions that
      lead to nonunion so that the complication may be better managed and possible
      avoided. PATIENTS AND METHODS: A retrospective review of mandible fractures in a
      major medical center was carried out on patients treated from 1994 through 1998.
      The nonunion cases were evaluated for factors such as age, sex, race, cause of
      fracture, location of fracture, delay until the patient obtained treatment, teeth
      in the fracture line, use of antibiotics, multiplicity of fractures, degree of
      fragmentation, medical problems, and drug and alcohol abuse. The adequacy of
      reduction and appropriateness of the fixation techniques were evaluated by
      analysis of the postoperative imaging studies. Postoperative occlusion and
      patient compliance were also included in the evaluation. RESULTS: Of the 906
      patients with 1,432 mandible fractures, there were 25 nonunion complications, for
      an incidence of 2.8%. Most patients with nonunion were men who had received the
      fracture as a result of an altercation. The nonunion was frequently noted in the
      body, and was almost twice as common (39% vs 17.6%) in patients with multiple
      fractures than in a randomly selected group who did not have the complication.
      Delayed treatment was noted in 8 of the patients, and teeth were present in the
      fracture line in another 8. Alcohol and drug abuse were prevalent, and 1 of 5 of
      the patients removed their fixation devices. Eight patients were believed to be
      stabilized inadequately, and 1 patient also had a poor reduction. Osteomyelitis
      was a common complication. CONCLUSIONS: The incidence of nonunion appears to be
      unchanged over time regardless of the varied and presumably advanced methods of
      fixation and reduction. Multiple fractures were a contributory factor, and the
      body of the mandible appeared to be a common site. Many patients had
      osteomyelitis associated with the nonunion. Inadequate stabilization or reduction
      were important causes. Other suspected contributory factors included failure to
      provide antibiotics, delay in treatment, teeth in the fracture line, alcohol and
      drug abuse, inexperience of the surgeon, and lack of patient compliance.

PMID- 10883690
TI  - Perioperative complications in corrective facial orthopedic surgery: a 5-year
      retrospective study.
AB  - PURPOSE: Frequency and severity of complications have a profound impact on
      referral patterns for facial orthopedic surgery. Therefore, a retrospective study
      was undertaken to determine the incidence of such problems in a large series of
      patients, with the intent to use these data to make possible changes in the
      perioperative protocol used in our clinic. PATIENTS AND METHODS: The files of all
      patients operated on between 1992 and 1996 were studied. These comprised 1,108
      patients with 1,872 osteotomy procedures. The following parameters were
      descriptively analyzed: airway obstruction, hemorrhage, hematoma, infection,
      neurosensory disturbances, unfavorable fractures, malposition of condyles and
      nasal septum, and vascularization problems. RESULTS: The most frequent
      complication was impairment of trigeminal nerve function. In 31.5% of the
      mandibular base osteotomies, 43.6% of the combined mandibular base and chin
      osteotomies, and 13% of the chin osteotomies, lip sensibility was decreased
      immediately postoperatively. After 1 year, this number was reduced to
      approximately 5%. The function of 17 lingual nerves and 45 infraorbital nerves
      was temporarily impaired. A wound infection was next in frequency. Fifty-three
      infections (mandible-to-maxilla ratio, 2.5:1) were treated with drainage under
      local anesthesia and antibiotic therapy. Loss of part or all of an osteotomized
      segment did not occur. Other complications were rare and/or temporary.
      CONCLUSIONS: The most frequent complication was impairment of inferior alveolar
      nerve function. Life-threatening complications were not encountered. The
      frequency of infections (<5%) requires further consideration regarding ways to
      reduce the incidence.

PMID- 10883691
TI  - Bone gap healing in the dog using recombinant human bone morphogenetic protein-2.
AB  - PURPOSE: This study investigated bone gap healing in a zygomatic arch defect
      using recombinant human bone morphogenetic protein-2 (rhBMP-2; Genetics
      Institute, Andover, MA) in an absorbable collagen sponge (ACS) carrier. METHODS:
      Zygomatic arch osteotomies were completed 15 mm apart and the arch was mobilized
      in 6 adult female mongrel dogs. The segment was then repositioned laterally 8 to
      10 mm and secured with a titanium reconstruction plate. Bone gaps in either the
      right or left arches received rhBMP-2, with the contralateral side being left
      empty in 4 animals and the defects received buffer/ACS without rhBMP-2 in 2
      animals as controls. Submentovertex radiographs were taken immediately
      postoperatively and every 4 weeks until killing at 12 weeks. RESULTS: Clinical
      evaluation indicated no significant differences in the degree of inflammation
      between the groups. However, the rhBMP-2 sites were found to be firm on
      palpation, in contrast to a soft tissue defect palpated in the control sites.
      Radiographic examination showed significant bone formation in all rhBMP-2 grafted
      sites as early as 4 weeks. The radiopacity of the bone continued to increase over
      the time of this study. Five of six control sites did not show bone formation
      through the course of this study. In addition to lack of bone formation, 5 of 6
      control sites showed collapse of the repositioned arch. All arches in the rhBMP-2
      sites remained in their lateral position and formed bone in the gaps. In 2
      animals, bone formation moderately exceeded the confines of the gap, and in 2
      animals excessive bone formation occurred. CONCLUSIONS: This study confirms that
      rhBMP-2 has the potential to be used to stimulate bone gap healing in the
      craniofacial complex.

PMID- 10883692
TI  - Cartilage formation by cultured chondrocytes in a new scaffold made of poly(L
      lactide-epsilon-caprolactone) sponge.
AB  - PURPOSE: This study investigated the ability of chondrocytes grown in culture and
      inoculated into a newly developed biodegradable sponge to form ectopic cartilage
      tissue. MATERIALS AND METHODS: Chondrocytes obtained from costochondral cartilage
      dissected from Lewis rats were cultured to allow proliferation and then were
      inoculated into a sponge consisting of a biodegradable polymer, poly (L-lactide
      epsilon-caprolactone). The composites of chondrocytes and sponge were
      transplanted subcutaneously into Nude mice and removed after 4 weeks for
      histologic and Northern blot analysis. RESULTS: Staining with hematoxylin and
      eosin showed the formation of a cartilage-like structure in the sponge. Northern
      blot analysis of the total RNA in the composites showed the presence of aggrecan
      transcripts of about 9 kb. CONCLUSION: The poly (L-lactide-epsilon-caprolactone)
      sponge system, is suitable as a matrix for tissue-engineered cartilage.

PMID- 10883693
TI  - Study of mandibular fracture repair using quantitative radiodensitometry: a
      comparison between maxillomandibular and rigid internal fixation.
AB  - PURPOSE: This prospective study evaluated mandibular fracture repair after either
      maxillomandibular fixation (MMF) or rigid internal fixation (RIF) using the
      computer-assisted densitometric image analysis (CADIA) system. PATIENTS AND
      METHODS: Fifty-two patients, 32 treated by MMF and 20 by RIF, were studied. Five
      postoperative panoramic radiographs were performed on each patient (immediately
      postoperatively and at 15, 30, 60, and 90 days) and the changes occurring in the
      optical density of the bone at and around the fracture line were analyzed.
      RESULTS: An increase in optic density was observed in both groups at 15 days
      after treatment. At 30 days, a decrease in optical density was observed in both
      groups, being significantly greater in the MMF group. In the measurements
      performed at 60 days, an increased density was found in the RIF group, but the
      rate of optical density increase was more rapid in the MMF group. During the
      third month, the rates of optical density increase were similar in the 2 groups.
      CONCLUSIONS: The use of RIF results in more rapid bone mineralization than the
      use of MMF.

PMID- 10883694
TI  - Genioplasty: a case for advancement osteotomy.
AB  - Despite personal preferences and training background that may influence the
      choice of which genioplasty technique to use, the osteoplastic technique has a
      better patient satisfaction rate (albeit slight), better soft tissue
      predictability, and less detrimental postoperative complications when compared
      with alloplastic augmentation of the chin. In addition, the osteoplastic
      technique is a more versatile procedure that can be used to correct any type of
      chin deformity and it has less of the limitations and contraindications
      associated with the alloplastic techniques.

PMID- 10883695
TI  - Genioplasty: a case for alloplastic chin augmentation.

PMID- 10883696
TI  - Massive proptosis of the globe.

PMID- 10883697
TI  - Recurrent ameloblastoma: report of 2 cases.

PMID- 10883698
TI  - Hemolytic anemia in a glucose-6-phosphate dehydrogenase-deficient patient
      triggered by a maxillofacial infection.

PMID- 10883699
TI  - Congenital infiltrating lipomatosis of the face: case report.

PMID- 10883700
TI  - Basal cell adenocarcinoma of the minor salivary gland: a case report.

PMID- 10883701
TI  - Spontaneous compartment syndrome occurring postoperatively in 2 oral surgery
      patients.

PMID- 10883702
TI  - Intramuscular lipoma of the cheek: a case report.

PMID- 10883703
TI  - Pseudoaneurysm of the superficial temporal artery treated by embolization: report
      of a case.

PMID- 10883704
TI  - Moldability of the callus after distraction osteogenesis.

PMID- 10883705
TI  - Not an age of depression after all? Incidence rates may be stable over time.

PMID- 10883706
TI  - Searching the schizophrenic brain for temporal lobe deficits: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Several empirical studies have found temporal lobe impairments in
      many patients with schizophrenia. The strength and consistency of this evidence,
      however, has not been evaluated and synthesized quantitatively. Hence, we ask to
      what extent are temporal cortices really defective in schizophrenia? METHODS:
      Meta-analytical methods were used to determine the magnitude of evidence in
      support of structural and physiological temporal-hippocampal system deficits in
      schizophrenia. We report effect sizes from studies since 1980 that used
      structural (CT, MRI) and functional (SPECT, PET) neuroimaging methods. RESULTS:
      Both structural and functional imaging literatures are distinguished by
      heterogeneity whereby most patients show normative temporal function and
      structure, a minority shows diminished values and some patients demonstrate
      augmented function and structure rather than a deficit. CONCLUSIONS: The findings
      are hard to incorporate within single disease models that propose major
      involvement of the temporal system in schizophrenia, at least at the degree of
      resolution obtained with current imaging technology.

PMID- 10883707
TI  - Incidence of depression in the Stirling County Study: historical and comparative
      perspectives.
AB  - BACKGROUND: The Stirling County Study provides a 40-year perspective on the
      epidemiology of psychiatric disorders in an adult population in Atlantic Canada.
      Across samples selected in 1952, 1970 and 1992 current prevalence of depression
      was stable. This paper concerns time trends in annual incidence as assessed
      through cohorts selected from the first two samples. METHODS: Consistent
      interview data were analysed by a computerized diagnostic algorithm. The cohorts
      consisted of subjects at risk for a first depression: Cohort-1 (N = 575) was
      followed 1952-1970; Cohort-2 (N = 639) was followed 1970-1992. Life-table methods
      were used to calculate incidence rates and proportional hazards procedures were
      used for statistical assessment. RESULTS: Average annual incidence of depression
      was 4.5 per 1000 for Cohort-1 and 3.7 for Cohort-2. Differences by gender, age
      and time were not statistically significant. The stability of incidence and the
      similarity of distribution by gender and age in these two cohorts corresponds to
      findings about the two early samples. In contrast, current prevalence in the
      recent sample was distributed differently and showed an increase among women
      under 45 years. CONCLUSIONS: The stability of the incidence of depression
      emphasizes the distinctive characteristics of current prevalence in the recent
      sample and suggests that the dominance of women in rates of depression may have
      occurred among those born after the Second World War. The results offer partial
      support for the interpretation of an increase in depression based on
      retrospective data in other recent studies but they indicate that the increase is
      specific to women.

PMID- 10883708
TI  - Predictors of change in anxiety symptoms of older persons: results from the
      Longitudinal Aging Study Amsterdam.
AB  - BACKGROUND: Data on the course of anxiety in late life are scarce. The present
      study sets out to investigate the course of anxiety, as measured by the HADS-A
      (Zigmond & Snaith, 1983) in community dwelling older persons, and to evaluate
      predictive factors for change over 3 years in anxiety symptoms following the
      vulnerability/stress model. METHOD: Based on the first anxiety assessment, two
      cohorts were formed: subjects with and subjects without anxiety symptoms. In the
      non-anxious cohort (N = 1602) we studied risk factors for the development of
      anxiety symptoms; in the anxious cohort (N = 563) the same factors were evaluated
      on their predictive value for restitution of symptoms. Risk factors included
      vulnerability factors (demographics, health status, personality characteristics
      and social resources) and stressors (life events occurring in between both
      anxiety assessments). Logistic regression models estimated the effects of
      vulnerability factors, stress and their interaction on the likelihood of becoming
      anxious and chronicity of anxiety symptoms. RESULTS: It was indicated that the
      best predictors for becoming anxious were being female, high neuroticism,
      hearing/eyesight problems and life-events. Female sex and neuroticism also
      increased the likelihood of chronicity of anxiety symptoms in older adults, but
      life events were not related to chronicity. The main stressful event in late life
      associated with anxiety was death of one's partner. Vulnerability factors and
      stress added on to each other rather than their interaction being associated with
      development or chronicity of anxiety. CONCLUSION: The vulnerability/stress model
      offers a useful framework for organizing risk factors for development and
      chronicity of anxiety symptoms in older persons, but no support was attained for
      the hypothesis that vulnerability and stress amplify each others effects.
      Finally, the results indicate to whom preventive efforts should be directed:
      persons high in neuroticism, women, and those who experience distressing life
      events.

PMID- 10883709
TI  - The stability of child abuse reports: a longitudinal study of the reporting
      behaviour of young adults.
AB  - BACKGROUND: The aims of this study were to use longitudinal report data on
      physical and sexual abuse to examine the stability and consistency of abuse
      reports. METHODS: The study was based on the birth cohort of young people studied
      in the Christchurch Health and Development Study. At ages 18 and 21 years, these
      young people were questioned about their childhood exposure to physical
      punishment and sexual abuse. Concurrent with these assessments, sample members
      were also assessed on measures of psychiatric disorder and suicidal behaviour.
      RESULTS: Reports of childhood sexual abuse and physical punishment were
      relatively unstable and the values of kappa for test-retests of abuse reporting
      were in the region of 0.45. Inconsistencies in reporting were unrelated to the
      subject's psychiatric state. Latent class analyses suggested that: (a) those not
      abused did not falsely report being abused; and (b) those who were abused
      provided unreliable reports in which the probability of a false negative response
      was in the region of 50%. Different approaches to classifying subjects as abused
      led to wide variations in the estimated prevalence of abuse but estimates of the
      relative risk of psychiatric adjustment problems conditional on abuse exposure
      remained relatively stable. CONCLUSIONS: There was substantial unreliability in
      the reporting of child abuse. This unreliability arose because those who were
      subject to abuse often provided false negative reports. The consequences of
      errors in reports appear to be: (a) that estimates of abuse prevalence based on a
      single report are likely to seriously underestimate the true prevalence of abuse;
      while (b) estimates of the relative risk of psychiatric adjustment problems
      conditional on abuse appear to be robust to the effects of reporting errors.

PMID- 10883710
TI  - Information processing deficits in relatives of manic depressive patients.
AB  - BACKGROUND: The importance of genetic factors in the aetiology of manic
      depressive illness (MDI) has been repeatedly confirmed and indicators of
      vulnerability to the illness in families with affective disorders are needed.
      Abnormal event-related potentials (ERP) may be markers of genetic vulnerability
      to mental illness. Long latency and low amplitude of P300 have consistently been
      reported in schizophrenic patients and their relatives. A few studies have also
      shown P300 deficits in MDI patients, but no ERP study has been performed on their
      relatives. METHODS: ERPs were recorded during an auditory oddball task in 19
      relatives belonging to families with two or more bipolar patients and in controls
      with no familial or personal history of affective disorders. The relatives were
      selected as having no affective disorders on a lifetime basis, but eight had an
      anxiety disorder. RESULTS: In all relatives, a lower P300 amplitude and a longer
      P300 latency was found, with much longer reaction time and post-N200 duration
      till button-press than controls. A lack of P300 amplitude dominance in the right
      hemisphere was also found in relatives in comparison with controls. There also
      appeared to be a frontal predominance of ERP abnormalities in relatives.
      CONCLUSION: We report the first evidence of deficits in reaction time and in P300
      amplitude and latency, and a lack of P300 right-sided dominance, in relatives of
      manic-depressive patients. This pattern may constitute an endophenotypic marker
      of manic-depressive disorder.

PMID- 10883711
TI  - Impaired distractor inhibition on a selective attention task in unmedicated,
      depressed subjects.
AB  - BACKGROUND: Impaired distractor inhibition may contribute to the selective
      attention deficits observed in depressed patients, but studies to date have not
      tested the distractor inhibition theory against the possibility that processes
      such as transient memory review processes may account for the observed deficits.
      A negative priming paradigm can dissociate inhibition from such a potentially
      confounding process called object review. The negative priming task also isolates
      features of the distractor such as colour and location for independent
      examination. METHOD: A computerized negative priming task was used in which
      colour, identification and location features of a stimulus and distractor were
      systematically manipulated across successive prime and probe trials. Thirty-two
      unmedicated subjects with DSM-IV diagnoses of non-psychotic unipolar depression
      were compared with 32 age, sex and IQ matched controls. RESULTS: Depressed
      subjects had reduced levels of negative priming for conditions where the colour
      feature of the stimulus was repeated across prime and probe trials but not when
      identity or location was the repeated feature. When both the colour and location
      feature were the repeated feature across trials, facilitation in response was
      apparent. CONCLUSIONS: The pattern of results supports studies that found reduced
      distractor inhibition in depressed subjects, and suggests that object review is
      intact in these subjects. Greater impairment in negative priming for colour
      versus location suggests that subjects may have greater impairment in the visual
      stream associated with processing colour features.

PMID- 10883712
TI  - Increased cortical inhibition in depression: a prolonged silent period with
      transcranial magnetic stimulation (TMS).
AB  - BACKGROUND: Motor slowing in depression may be associated with a relative
      dopaminergic (DA) deficit. Bradykinesia in Parkinson's syndrome is associated
      with an abnormally short silent period (SP) using transcranial magnetic
      stimulation (TMS). We hypothesized that depression would also be associated with
      a short SP. METHODS: Sixteen patients with DSM-IV depression and 19 matched
      controls participated. SPs were elicited by exercising the contralateral abductor
      policis brevis (APB) during TMS. RESULTS: The SP was significantly increased in
      the patient group. No correlation was found between SP and depression score.
      CONCLUSION: A long SP suggests increased motor cortical inhibition in depression.
      This finding is inconsistent with the hypothesis of behavioural motor slowing in
      depression being associated with Parkinsonian-like mechanisms including the
      dopaminergic deficit. There is a need for studies incorporating larger patient
      groups to investigate potential correlations between SP and depression indices.

PMID- 10883714
TI  - Right lower prefronto-parietal cortical dysfunction in akinetic catatonia: a
      combined study of neuropsychology and regional cerebral blood flow.
AB  - BACKGROUND: Catatonia is a psychomotor syndrome that can be characterized by
      behavioural, affective and motor abnormalities. In order to reveal further
      underlying pathophysiological mechanisms of psychomotor disturbances in catatonia
      we investigated neuropsychological function and regional cerebral perfusion (r
      CBF) in a combined study. METHODS: Ten catatonic patients were investigated with
      Tc-99mECD brain SPECT and compared with 10 psychiatric (similar age, sex,
      medication and underlying psychiatric diagnosis but without catatonic syndrome)
      and 20 healthy controls. Neuropsychological measures included tests for general
      intelligence, attention, executive functions and right parietal visual-spatial
      abilities. Correlational analyses were performed between neuropsychological
      measures, catatonic symptoms and r-CBF. RESULTS: Catatonic patients showed a
      significant decrease of r-CBF in right lower and middle prefrontal and parietal
      cortex compared with psychiatric and healthy controls as well as significantly
      poorer performance in visual-spatial abilities associated with right parietal
      function. Correlational analysis revealed significant correlations between visual
      spatial abilities and right parietal r-CBF only in psychiatric and healthy
      controls but not in catatonic patients. In contrast, attentional measures
      correlated significantly with motor symptoms, visual-spatial abilities and right
      parietal r-CBF in catatonia only but not in psychiatric or in healthy controls.
      CONCLUSION: Findings are preliminary but suggest right lower prefronto-parietal
      cortical dysfunction in catatonia, which may be closely related to psychomotor
      disturbances.

PMID- 10883713
TI  - Schizophrenia, temporal lobe epilepsy and psychosis: an in vivo magnetic
      resonance spectroscopy and imaging study of the hippocampus/amygdala complex.
AB  - BACKGROUND: We have used proton magnetic resonance imaging and spectroscopy to
      measure hippocampus/amygdala volumes and anterior hippocampal metabolite
      concentrations (N-acetyl aspartate (NAA), creatine/phosphocreatine and choline)
      in subjects with temporal lobe epilepsy (TLE), schizophrenia and in normal
      controls. METHOD: Four groups of right-handed patients were selected: 12 with TLE
      and psychosis (EP), 12 with TLE and no psychosis (ENP), 26 with schizophrenia,
      and 38 normal controls. Imaging and spectroscopy were performed with a 1.5T Signa
      GE scanner. RESULTS: The schizophrenia group showed a significant left-sided
      reduction in all metabolites. In the epilepsy groups NAA was reduced bilaterally.
      The NAA reduction in the EP group was greater than in the ENP group, especially
      on the left, although the result did not reach significance. Total
      hippocampus/amygdala volumes showed no significant differences in any of the
      groups when compared with normal controls. When compared with controls
      significant, specific regional volume reductions were present bilaterally in the
      EP group and in the left hippocampus/amygdala in schizophrenia. The regional
      volume reduction found in schizophrenia was also present in EP but not in ENP.
      CONCLUSION: Spectroscopic abnormalities were more pronounced in the epilepsy
      groups and were bilateral, and abnormalities in schizophrenia were left sided.
      Specific regional hippocampus/amygdala volume reductions were more marked in the
      EP group and were bilateral. Left-sided regional volume reduction identified in
      the dominant hemisphere of schizophrenics was also present in EP patients, but
      not in ENP, suggesting that this region in the left temporal lobe may be
      significant in the aetiology of psychosis. This is further supported by the
      predominantly left-sided NAA reduction in schizophrenia. High resolution
      morphometric studies may identify specific regions of the brain associated with
      the development of psychosis.

PMID- 10883715
TI  - Intra-uterine physical growth in schizophrenia: evidence confirming excess of
      premature birth.
AB  - BACKGROUND: Many studies have suggested a possible aetiological role for
      obstetric complications in the development of schizophrenia. We focused on
      prenatal physical growth in schizophrenia, a contentious issue in the literature.
      METHODS: We compared gestational age at birth, birth weight (BW) and birth head
      circumference (BHC) between 312 schizophrenics and 517 controls, and between 187
      schizophrenics and their matched healthy siblings. Information on obstetric
      histories was obtained from the Maternal and Child Health Handbooks (i.e.
      contemporaneous records). RESULTS: Gestational age at birth was significantly
      earlier in the schizophrenics than in the controls (P = 0.017). Pre-term birth
      (gestational age of 36 weeks or less) was more common in schizophrenics than in
      controls (8.0% v. 3.4%, P = 0.005, odds ratio 2.5). Low BW (2500 g or less) was
      more frequent in schizophrenics than in controls (9.6% v. 4.6%, P = 0.005, odds
      ratio 2.2). The schizophrenics had significantly lighter BW (P = 0.0003) and
      tended to have smaller BHC (P = 0.081) compared with controls. However, multiple
      regression analysis showed that there was no significant difference in BW or BHC
      between the schizophrenics and controls when gestational age and maternal weight
      were controlled. There was no significant difference in BW or BHC between
      schizophrenics and their siblings, although the schizophrenics tended to be born
      at earlier gestational age than their siblings. CONCLUSIONS: Our results suggest
      that prematurity at birth is associated with a risk of developing schizophrenia
      in adulthood. When gestational age and maternal body weight were allowed for,
      there was no evidence that schizophrenics tend to have lower mean BW or smaller
      BHC.

PMID- 10883716
TI  - Dimensions of the Mini-Mental State Examination among community dwelling older
      adults.
AB  - BACKGROUND: Little work has been published on the internal structure of the Mini
      Mental State Examination (MMSE), one of the most widely used instruments for
      grading cognitive status in clinical settings and field research. METHODS: MMSE
      responses from a sample of older adults (50-98 years) in five US sites (N = 8556)
      were analysed. RESULTS: A five-factor solution was found to be most appropriate.
      The first factor (concentration) had large loadings with serial sevens and spell
      world backwards items. The second factor (language and praxis) had large loadings
      with naming, follow command and praxis items. The third factor (orientation) had
      loadings with orientation to time and place items. The fourth factor (memory) had
      large loadings with delayed recall items and the fifth (attention) had large
      loadings with immediate registration items. CONCLUSIONS: We found that the MMSE
      is essentially unidimensional; nevertheless, evidence was revealed suggesting
      that the MMSE is a multidimensional assessment instrument. Dimensions revealed in
      this sample correspond directly to MMSE sections articulated by the developers of
      the instrument. These findings have not been reported in previous factor analyses
      of the MMSE. The findings support the construct validity of the MMSE as a measure
      of cognitive mental state among community dwelling older adults.

PMID- 10883717
TI  - Early detection of Alzheimer's disease using the Cambridge Cognitive Examination
      (CAMCOG).
AB  - BACKGROUND: Dementia screening instruments, such as the Cambridge Cognitive
      Examination (CAMCOG), measure a variety of cognitive functions. However, memory
      impairment generally is the first sign of Alzheimer's disease (AD). It seems
      logical, therefore, to use only memory-related items for the early detection of
      AD. We divided the CAMCOG into a memory section and a non-memory section, and
      tested the hypothesis that the memory section predicts AD better than the non
      memory section. We also provide normative data for both sections. METHODS: Normal
      subjects (N = 169) and patients with incident AD (i.e. satisfying AD criteria
      between 1 and 3 years from baseline: N = 25) were participants in the Amsterdam
      Study of the Elderly (AMSTEL), a population-based longitudinal study on cognitive
      decline and dementia. Patients with prevalent AD (i.e. satisfying AD criteria at
      baseline: N = 155) were either recruited in a memory clinic or came from AMSTEL.
      Normal subjects were cognitively intact at baseline and remained so for at least
      3 years. The CAMCOG was administered to all subjects. AD was diagnosed by DSM-III
      R criteria. RESULTS: Logistic regression analysis showed that the memory section
      was related to prevalent AD, whereas in multivariate analysis the non-memory
      section was not (after correction for the memory score and demographic
      characteristics). A similar analysis showed that the memory section predicted
      incident AD, as did a higher score on the non-memory section. The MMSE did not
      predict incident AD better than age alone. CONCLUSION: For the early detection of
      AD it is best to use the memory and non-memory sections separately instead of the
      total CAMCOG score.

PMID- 10883718
TI  - Differences in verbal behaviours of patients with and without emotional distress
      during primary care consultations.
AB  - BACKGROUND: In primary care consultations patients with emotional distress tend
      to give verbal cues or symptom reports with psychological or psychiatric
      contents. This study examined the cue behaviour defined not only by
      psychological, but also by medical, social and life episodes related contents in
      patients with and without emotional distress, recognized and not by their GP. The
      GP's verbal behaviour in relation to patients' cue emission was also
      investigated. METHOD: For the six participating GPs two groups of matched pairs
      of patients (N = 238) were created. The two groups comprised either patients
      considered by GPs as being without emotional distress or patients considered as
      emotionally distressed. Within each pair, one patient was a case (GHQ-12 score >
      2) and the other was the matched control (GHQ-12 score < 3). The medical
      interviews with these patients were transcribed and classified according to the
      Verona Medical Interview Classification System (VR-MICS). RESULTS: GHQ positive
      patients of both groups gave more cues in terms of total proportion than their
      matched controls (GHQ negative patients). The proportion of cues given by
      patients was related also to GP's verbal behaviour, increasing with closed
      psychosocial questions and decreasing with the use of active interview
      techniques. Attribution of emotional distress was more frequent when patients
      were high attenders and had a past psychiatric history. The content of cues
      changed in relation to GP's attribution: recognized patients gave more cues and
      more often with psychological content, patients not recognized as distressed gave
      mainly cues related to their lifestyle and life episodes. CONCLUSIONS: To improve
      the recognition of those emotionally distressed patients most likely to be missed
      GPs should increase their attention to cues related to life style and life
      episodes.

PMID- 10883719
TI  - Perceived need for mental health care, findings from the Australian National
      Survey of Mental Health and Well-being.
AB  - BACKGROUND: The Australian National Survey of Mental Health and Well-being was
      designed to detect and describe psychiatric morbidity, associated disability,
      service use and perceived need for care. The survey employed a single-phase
      interview methodology, delivering a field questionnaire to a clustered
      probability sample of 10,641 Australians. Perceived need was sampled with an
      instrument designed for this survey, the Perceived Need for Care Questionnaire
      (PNCQ). This questionnaire gathers information about five categories of perceived
      need, assigning each to one of four levels of perceived need. Reliability and
      validity studies showed satisfactory performance of the instrument. METHODS:
      Perceived need for mental health care in the Australian population has been
      analysed using PNCQ data, relating this to diagnostic and service utilization
      data from the above survey. RESULTS: The survey findings indicate that an
      estimated 13.8% of the Australian population have perceived need for mental
      health care. Those who met interview criteria for a psychiatric diagnosis and
      also expressed perceived need make up 9.9% of the population. An estimated 11.0%
      of the population are cases of untreated prevalence, a minority (3.6% of the
      population) of whom expressed perceived need for mental health care. Among
      persons using services, those without a psychiatric diagnosis based on interview
      criteria (4.4% of the population), showed high levels of perceived met need.
      CONCLUSIONS: The overall rate of perceived need found by this methodology lies
      between those found in the USA and Canada. The findings suggest that service use
      in the absence of diagnosis elicited by survey questionnaires may often represent
      successful intervention. In the survey, untreated prevalence was commonly not
      accompanied by perceived need for mental health care.

PMID- 10883720
TI  - Current and residual functional disability associated with psychopathology:
      findings from the Netherlands Mental Health Survey and Incidence Study (NEMESIS).
AB  - BACKGROUND: Few population studies have investigated the functional disabilities
      that accompany specific psychiatric diagnoses. This study assesses the nature and
      strength of current and residual impairments in various functional domains of
      life. METHODS: Data were derived from the Netherlands Mental Health Survey and
      Incidence Study (NEMESIS), a prospective study in the Dutch general population
      aged 18 to 64 (N = 7147). Psychiatric diagnoses were based on the Composite
      International Diagnostic Interview; functional disability was assessed on the
      basis of the Short-Form-36 and the number of disability days. RESULTS:
      Psychopathology was associated with increased disability in social, emotional and
      physical domains of life. Disability levels varied by psychiatric diagnosis, with
      mood disorders showing the poorest levels of functioning, especially for vitality
      and social functioning; alcohol-related disorders were associated with few
      disabilities. Co-morbidity strongly aggravated the disability. The effect of
      contextual factors on disability was limited, although somatic ill health,
      unemployment and adverse youth history increased the likelihood of functional
      disability. The findings indicate that psychopathology can also have residual
      debilitating effects. CONCLUSIONS: Mental health care providers should be aware
      that the extent and the type of disability may vary with the different types of
      disorders and among different groups within the population. Since recovery from
      functional limitations may not be complete or may take more time than the
      remission of the psychiatric symptomatology, non-psychiatric follow-up care is
      needed. The high number of lost work days is relevant from an economic
      perspective. There is a need for illness-specific disability assessment
      instruments.

PMID- 10883721
TI  - Early and chronic stress and their relation to breast cancer.
AB  - BACKGROUND: The study examined the role of parental death and chronic depression
      with severe episodes in affecting risk of breast cancer. This avenue of research
      is in accord with oncology findings, which suggests that causative factors of
      breast cancer occur and develop over a period of 20 years or longer. METHODS:
      Participants consisted of 1213 women in the Baltimore Epidemiologic Catchment
      Area study surveyed in 1980 and followed through 1994-1995. They were assessed
      for depressive and anxious disorders, paternal death in childhood and relatively
      recent adverse life events prior to cancer hospitalization. RESULTS: In the
      course of the study, 29 women were hospitalized for breast cancer and 10 died of
      breast cancer. The psychosocial variables that predicted increased risk of breast
      cancer were maternal death in childhood (OR = 2.56, P < 0.001) and chronic
      depression with severe episodes (OR = 14.0, P < 0.001). Neither relatively recent
      life events nor other depressive and anxiety disorders were associated with
      increased risk. Maternal death and chronic depression with severe episodes were
      reported to have occurred at least 20 years prior to breast cancer
      hospitalization. CONCLUSIONS: Maternal death and chronic and severe depression
      occurred at least 20 years prior to breast cancer hospitalization and could have
      been involved in the causation or facilitation of cancer development. The authors
      suggest that meta-analysis of other prospective studies are needed to create
      larger groups of individuals with these stresses to confidently establish these
      variables as risk factors.

PMID- 10883722
TI  - Decreased working memory and processing speed mediate cognitive impairment in
      geriatric depression.
AB  - BACKGROUND: While neuropsychological dysfunction is common in geriatric
      depression, not all aspects of cognition are equally affected. It has been
      suggested that depressed patients are impaired only in tasks that make heavy
      demands on processing resources and that a resource decrement therefore underlies
      the neuropsychological decrements seen in geriatric depression. The present study
      examined whether processing resources in the form of working memory and
      information processing speed are decreased in depression and whether a decrease
      in these resources actually mediates neuropsychological impairment. METHODS:
      Measures of processing resources were administered to elderly depressed patients
      prior to treatment and to age-matched controls. Patients whose depression
      remitted were retested as were the controls. Subjects also received
      neuropsychological tests of episodic memory and visuospatial performance.
      RESULTS: Depressed patients performed significantly worse on measures of both
      processing speed and working memory. While performance on these measures improved
      in patients whose depression remitted, the amount of improvement was no greater
      than that seen in the controls with repeat testing. Hierarchical regression
      analyses showed that depression explained a significant amount of variance on the
      neuropsychological tasks. However, if the variance associated with processing
      resources was removed first, depression no longer accounted for a significant
      amount of neuropsychological variance. CONCLUSIONS: Processing resources are
      decreased in elderly depressed patients and this decrease in resources appears to
      mediate impairments in several areas of neuropsychological functioning including
      episodic memory and visuospatial performance. The resource decrement persists
      after remission of the depression and thus may be a trait marker of geriatric
      depression.

PMID- 10883723
TI  - Duration between onset and time of obtaining initial treatment among people with
      anxiety and mood disorders: an international survey of members of mental health
      patient advocate groups.
AB  - BACKGROUND: Self-report data obtained from members of advocate groups for
      patients with anxiety or mood disorders in 11 countries were used to study time
      to initial professional help-seeking after incident episodes. METHOD: Data were
      taken from 3516 self-administered questionnaires completed by members of GAMIAN,
      an international consortium of mental health patient advocate groups. Reports
      about age at onset and age at first seeking treatment were obtained
      retrospectively. RESULTS: Approximately 40% of respondents reported that they
      sought treatment in the same year as the first onset of their disorder. The
      median delay in help-seeking was 8 years for the remainder of respondents.
      Synthetic cohort analysis suggests that delays have decreased in recent cohorts.
      However, time to initial help-seeking in all cohorts and all countries was found
      to be inversely related to age at onset. CONCLUSIONS: Although caution is needed
      in generalizing the results beyond members of patient advocate groups, the key
      patterns found here were also found in previous analyses of general population
      surveys carried out in the US and Canada. The critical and consistent finding in
      all these studies is that presumably curable adolescents with early-onset
      disorders are, in effect, ignored by the treatment system in these countries.
      Aggressive outreach and intervention among early-onset cases might prove to be a
      cost-effective approach both to prevent the onset of secondary disorders and to
      improve success in treating primary disorders.

PMID- 10883724
TI  - Social and personal resources and the prevalence of phobic disorder in a
      community population.
AB  - BACKGROUND: Phobic disorder is one of the most prevalent psychiatric disorders in
      community populations and much attention has focused on the association of
      sociodemographic factors and social resources with the disorder. There has been
      little investigation of the more personal resources such as self-confidence,
      religiosity, social support and self-perceived health that may increase
      vulnerability. METHODS: We used a sample of 2914 community residents aged 18 or
      older who participated in the Duke University Epidemiologic Catchment Area Study
      to explore the relationship between both social and personal resources and the
      prevalence of DIS/DSM-III phobic disorder. RESULTS: The 1-month prevalence of any
      phobic disorder was 7.6%. In bivariate analyses, we found both race/ethnicity and
      gender differences in prevalence, with a higher prevalence of phobic disorder in
      African-Americans and females. Lower socio-economic status, rural residence and
      unmarried status were also associated with current prevalence. No association was
      found for social network and social interaction. Impaired subjective social
      support, low self-confidence, perceived poorer physical health and co-morbid
      psychiatric disorder were significantly associated with current prevalence in
      uncontrolled analyses, while associations between lack of a confidant as well as
      religiosity and phobic disorder were not. Female gender (OR = 1.7), perceived low
      self-confidence (OR = 2.0), and two interaction terms, age x co-morbid
      psychiatric disorder and race/ethnicity x perceived physical health were
      associated with phobic disorder in controlled analyses using logistic regression.
      CONCLUSIONS: We conclude that both social and personal resources, particularly
      self-confidence, co-morbidity and perceived physical health are important
      correlates of phobic disorder.

PMID- 10883725
TI  - Nithsdale schizophrenia surveys 21: a longitudinal study of National Adult
      Reading Test stability.
AB  - BACKGROUND: The stability of the National Adult Reading Test (NART) as a measure
      of pre-morbid intelligence in schizophrenia has not yet been satisfactorily
      established despite the widespread use of the NART in schizophrenia research.
      METHOD: We examined NART stability in a diverse group of 45 schizophrenic
      patients in a prospective longitudinal study over 6.5-7.5 years. RESULTS: The
      results showed that NART performance does not decline significantly with
      increasing duration of schizophrenic illness and that test-retest reliability,
      even over 6.5-7.5 years, is extremely high. DISCUSSION: Our results provide the
      necessary evidence that the NART can be used as a stable measure of pre-morbid
      intelligence in schizophrenia.

PMID- 10883726
TI  - Heterogeneity of cycloid psychoses: a latent class analysis.
AB  - BACKGROUND: Three hypotheses have been proposed in regard to the origin of
      cycloid psychoses: (1) they are an independent nosological entity; (2) they are
      atypical cases of affective disorders; and (3) they are a heterogeneous group of
      disorders. This study examined the heterogeneity hypothesis by attempting to
      delineate distinct affective and non-affective subgroups. METHODS: In 60 cases
      drawn from a classic study of cycloid psychoses by Perris (1974), latent class
      analysis was used to delineate subgroups. RESULTS: Two classes were identified in
      the analysis: one characterized by the convergence of affective symptoms and
      family history of affective disorders and the other by the relative paucity of
      such features. CONCLUSIONS: Cycloid psychoses are composed of at least two
      subgroups, distinguishable on the basis of symptoms and family history.

PMID- 10883727
TI  - Life events and prodromal symptoms in bulimia nervosa.
AB  - BACKGROUND: Little is known about the interaction of life events with prodromal
      symptoms in bulimia nervosa. METHODS: A semistructured research interview based
      on Paykel's Interview for Recent Life Events and on the Clinical Interview for
      Depression for eliciting prodromal symptoms was administered to 30 patients with
      bulimia nervosa and 30 healthy control subjects matched for sociodemographic
      variables. RESULTS: Patients reported significantly more stressful life events
      than controls. Most of the patients reported prodromal symptoms. Anorexia, low
      self-esteem, depressed mood, anhedonia, generalized anxiety and irritability were
      the most common prodromal symptoms. CONCLUSIONS: The prodromal phase of bulimia
      nervosa was found to be characterized by a combination of prodromal symptoms of
      affective type and stressful life events. Their joint occurrence may increase
      vulnerability to bulimia nervosa.

PMID- 10883728
TI  - The possibility of different forms of theory of mind impairment in psychiatric
      and developmental disorders.

PMID- 10883729
TI  - In vivo activity of pseudoguaianolide sesquiterpene lactones in acute and chronic
      inflammation.
AB  - The pseudoguaianolide sesquiterpene lactones 4-alpha-O-acetyl-pseudoguaian-6beta
      olide (1), hymenin (2), ambrosanolide (3), tetraneurin A (4), parthenin (5),
      hysterin (6) and confertdiolide (7) were evaluated for their ability to affect
      the inflammation responses induced by different agents. All the compounds showed
      activity against the 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced mouse ear
      edema. The ethyl phenylpropiolate (EPP)-induced mouse ear edema was inhibited by
      compounds 3, 5 and 7. However, when sesquiterpene-lactones were assayed on the
      arachidonic acid (AA)-induced mouse ear edema, none of them were active. The only
      sesquiterpene lactone orally active against the paw mouse edema induced by
      carrageenan was 7, which gave a 46% edema inhibition after 3 h. On the other
      hand, compounds 3, 5 and 7 reduced the serotonin-induced paw edema in mice,
      although compound 7 was inactive in presence of cycloheximide. In addition, the
      sesquiterpene lactones were assayed against the chronic inflammation induced by
      repeated application of TPA on mouse ear. Confertdiolide was the most active
      compound; it reduced the edema by 87% and had a more moderate effect against the
      leukocyte recruitment (36% reduction in myeloperoxidase (MPO) levels). A
      histological study of ear the samples treated with 7 presented no detectable
      morphological lesions such as those treated with dexamethasone. On the oxazolone
      induced delayed type hypersensitivity (DTH) only compounds 4 and 5 were active 24
      h after the challenge. Compound 5 affected polymorphonuclear leukocyte
      infiltration (69% reduction in MPO levels). The results suggest that the especial
      chemical structure and spatial conformation of confertdiolide may facilitate its
      anti-inflammatory effect.

PMID- 10883730
TI  - Effects of selected herbicides on cytokine production in vitro.
AB  - To evaluate possible deleterious effects of commonly used herbicides on
      leukocytes, cytokine production was selected as a sensitive indicator. After in
      vitro exposure of human peripheral blood mononuclear cells from normal donors,
      the production of all 3 cytokines tested--interferon-gamma (a type 1 cytokine),
      interleukin-5 (a type 2 cytokine) and tumor necrosis factor-alpha (an
      inflammatory cytokine)--was impaired by up to 70, 50 and 70% respectively in a
      concentration-dependent manner in cultures exposed to atrazine (0.03-3 microM in
      1% dimethylsulfoxide, DMSO). The effect paralleled that seen with dexamethasone,
      a known immunosuppressive agent. Other pesticides also dissolved in DMSO-
      mecoprop, simazine or MCPA (each up to 1 microM)--or dissolved in phosphate
      buffered saline--diuron (up to 1 microM), isoproturon (up to 3 microM), metoxuron
      (up to 8 microM) or metamitron (up to 80 microM)--showed no concentration-related
      effects on cytokine production. There was, however, an inhibition of IFN-gamma
      and TNF-alpha production by simazine, metoxuron and mecoprop and of all three
      cytokines tested by diuron. MCPA (0.01 and 0.1 microM) stimulated the production
      of TNF-alpha. Thus, exposure to herbicides leading to plasma levels in the
      micromolar range induces imbalance in cytokine production.

PMID- 10883731
TI  - Investigating the dual nature of endothelin-1: ischemia or direct arrhythmogenic
      effect?
AB  - Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, which may also elicit
      severe ventricular arrhythmias. The aims of our study were to compare the effects
      of total left anterior descending coronary artery (LAD) occlusion to
      intracoronary (ic.) ET-1 administration and to investigate the pathomechanism of
      ET-1 induced arrhythmias in 3 groups of anesthetized, open-chest mongrel dogs. In
      group A (n=10) a total LAD occlusion was carried out for 30 min, followed by a 60
      min reperfusion period. In groups B and C ET-1 was administered into LAD for 30
      min at a rate of 30 pmol/min (n=6) and 60 pmol/min (n=8). Epi- and endocardial
      monophasic action potential (MAP) recordings were performed to detect
      electrophysiologic changes and ischemia Blood samples for lactate measurements
      were collected from the coronary sinus (CS) and from the femoral artery. Infrared
      imaging was applied to follow epimyocardial heat emission changes. At the end of
      the ET-1 infusion period coronary blood flow (CBF) was reduced significantly in
      groups B and C (deltaCBF30MIN B: 21+/-2%, p<0.05; C: 35+/-2%, p<0.05), paralleled
      by a significant epimyocardial temperature decrease in group C (deltaT30MIN: 
      0.65+/-0.29 degrees C, p<0.05). Two dogs died of ventricular fibrillation (VF) in
      the reperfusion period in group A. Ventricular premature contractions and non
      sustained ventricular tachycardic episodes appeared in group B, whereas six dogs
      died of VF in group C. Significant CS lactate level elevation indicating ischemia
      was observed only in group A from the 30th min occlusion throughout the
      reperfusion period (control vs. 30 min: 1.3+/-0.29 vs. 2.2+/-0.37 mmol/l,
      p<0.05). Epi- and endocardial MAP durations (MAPD90) and left ventricular
      epicardial (LV(EPI)) upstroke velocity decreased significantly in group A in the
      occlusion period. ET-1 infusion significantly increased LV(EPI) MAPD90 in group B
      and both MAPD90-s in group C. In conclusion, ischemic MAP and CS lactate changes
      were observed only in group A. Although ET-1 reduced CBF significantly in groups
      B and C, neither MAP nor lactate indicated ischemic alterations. ET-1 induced
      major ventricular arrhythmias appeared before signs of myocardial ischemia
      developed, though reduced CBF presumably contributed to sustaining the
      arrhythmias.

PMID- 10883732
TI  - Facilitation of spontaneous acetylcholine release induced by activation of cAMP
      in rat neuromuscular junctions.
AB  - Regulation of neurotransmitter release is thought to involve modulation of the
      release probability by protein phosphorylation. Activation of the cAMP-protein
      kinase A (PKA) pathway has been shown to facilitate synaptic transmission in
      mammalian neuromuscular synapses, although the relevant phosphorylation targets
      are mostly unknown. We found that the inhibitor of the phosphodiesterase
      aminophylline (1 mM AMIN), the membrane-permeable analog of cAMP, 8-Br-cAMP (5
      mM) and, the direct adenylate cyclase activator, forskolin (20 microM), induced
      an increase of miniature end-plate potentials (MEPPs) frequency in rat
      neuromuscular junctions. We investigated the possible involvement of the voltage
      dependent calcium channels (VDCC), since these proteins are known to be
      phosphorylated by PKA. But this possibility was ruled out, since the increase in
      MEPPs frequency was not attenuated by the VDCC blocker Cd2+ (100 microM) and it
      was observed when AMIN was studied on hyperosmotic response, which is independent
      of [Ca2+]o and of Ca2+ influx through the VDCC. The lack of action of AMIN on
      MEPPs frequency when [Ca2+]i was diminished by exposing the preparations to zero
      Ca2+-EGTA solution (isotonic condition) or when nerve terminals were loaded with
      a permeant Ca2+ chelator (BAPTA-AM) (hypertonic condition), indicate that cAMP
      mediated presynaptic facilitation is a function of nerve terminal Ca2+
      concentration. We also found that AMIN exerted a comparable increase in MEPPs
      frequency in control and high K+ (10 and 15 mM), suggesting a single mechanism of
      action for spontaneous and K+-induced secretion.

PMID- 10883733
TI  - Positive association of endothelial nitric oxide synthase gene polymorphism with
      hypertension in northern Japan.
AB  - Vascular endothelial cells produce nitric oxide (NO), which contributes to the
      regulation of blood pressure and regional blood flow. Although Endothelial NO
      synthase (eNOS) gene polymorphisms have been shown to have a positive association
      with coronary artery disease, the linkage between eNOS gene polymorphisms and
      hypertension has been controversial. In the present study, therefore, we
      identified genotypes for Glu298Asp and variable number tandem repeats in intron 4
      (4b/a) in 183 hypertensive and 193 normotensive populations. The Glu298Asp
      variant had a significant association with hypertension (odds ratio, 1.8; 95%
      confidence interval, 1.1-3.0). The allele frequencies of 298Asp for Glu298 in
      hypertensive patients were significantly higher than those in normotensive
      subjects (0.128 vs 0.080, p<0.05). Diastolic and mean arterial blood pressures
      were significantly higher in hypertensive subjects with the 298Asp allele than
      those without the variant allele (p<0.05). However, disequilibrium of 4b/a
      polymorphism was absent between these two groups. These results suggest that the
      Glu298Asp variant may be a genetic susceptibility factor for hypertension.

PMID- 10883734
TI  - Mechanism of mifepristone-induced spasmolytic effect on isolated rat uterus.
AB  - Mifepristone, a synthetic 19-norsteroid, relaxed the KCl-induced tonic
      contraction in isolated rat uterus in a concentration-dependent way and CaCl2
      (0.1 to 10 mM) counteracted it. This effect was similar to other steroids
      although the mechanisms involved are unclear. Before adding the contracturant,
      tissue was incubated with actinomycin D (10 microM), cycloheximide (300 microM),
      TPCK (3 and 10 microM), Rp-cAMPS (30 microM), DDA (100 microM) and H-7 (1
      microM). None of these modified the relaxing effect of mifepristone. Incubation
      with drugs that interfere with cGMP such as a nucleotide analogue DDG (100
      microM), a soluble guanylyl cyclase inhibitor ODQ (1 microM) and an inhibitor of
      protein kinase G 8pCPTcGMPS (1 microM) significantly modified the effect of
      mifepristone, increasing its IC50.

PMID- 10883735
TI  - Carbohydrate specificity of an agglutinin isolated from the root of Trichosanthes
      kirilowii.
AB  - The root of Trichosanthes kirilowii, which has been used as Chinese folk medicine
      for more than two thousand years, contains a Gal specific lectin (TKA). In order
      to elucidate its binding roles, the carbohydrate specificities of TKA were
      studied by enzyme linked lectinosorbent assay (ELLSA) and by inhibition of lectin
      glycoform binding. Among glycoproteins (gp) tested, TKA reacted strongly with
      complex carbohydrates with Galbeta1-->4GlcNAc clusters as internal or core
      structures (human blood group ABH active glycoproteins from human ovarian cyst
      fluids, hog gastric mucin, and fetuin), porcine salivary glycoprotein and its
      asialo product, but it was inactive with heparin and mannan (negative control).
      Of the sugar inhibitors tested for inhibition of binding, Neu5Ac alpha2-
      >3/6Galbeta1-->4Glc was the best and about 4, 14.6 and 27.7 times more active
      than Galbeta1-->4GlcNAc(II), Galbeta1-->3GalNAc(T) and Gal, respectively. From
      these results, it is suggested that this agglutinin is specific for terminal or
      internal polyvalent Galbeta1-->4GlcNAcbeta1-->, terminal Neu5Ac alpha2-
      >3/6Galbeta1-->4Glc and cluster forms of Galbeta1-->3GalNAc alpha residues. The
      unusual affinity of TKA for terminal and internal Galbeta1-->glycotopes may be
      used to explain the possible attachment roles of this agglutinin in this folk
      medicine to target cells.

PMID- 10883736
TI  - Protective effects of thymoquinone and desferrioxamine against hepatotoxicity of
      carbon tetrachloride in mice.
AB  - The effects of thymoquinone (TQ) and desferrioxamine (DFO) against carbon
      tetrachloride (CCl4)-induced hepatotoxicity were investigated. A single dose of
      CCl4 (20 microl/kg, i.p.) induced hepatotoxicity, manifested biochemically by
      significant elevation of activities of serum enzymes, such as alanine
      transaminase (ALT, EC: 2.6.1.2) , aspartate transaminase (AST, EC: 2.6.1.1) and
      lactate dehydrogenase (LDH, EC: 1.1.1.27). Hepatotoxicity was further evidenced
      by significant decrease of total sulfhydryl (-SH) content, and catalase (EC:
      1.11.1.6) activity in hepatic tissues and significant increase in hepatic lipid
      peroxidation measured as malondialdhyde (MDA). Pretreatment of mice with DFO (200
      mg/kg i.p.) 1 h before CCl4 injection or administration of TQ (16 mg/kg/day,
      p.o.) in drinking water, starting 5 days before CCl4 injection and continuing
      during the experimental period, ameliorated the hepatotoxicity induced by CCl4,
      as evidenced by a significant reduction in the elevated levels of serum enzymes
      as well as a significant decrease in the hepatic MDA content and a significant
      increase in the total sulfhydryl content 24 h after CCl4 administration. In a
      separate in vitro assay, TQ and DFO inhibited the non-enzymatic lipid
      peroxidation of normal mice liver homogenate induced by Fe3+/ascorbate in a dose
      dependent manner. These results indicate that TQ and DFO are efficient
      cytoprotective agents against CCl4-induced hepotoxicity, possibly through
      inhibition of the production of oxygen free radicals that cause lipid
      peroxidation.

PMID- 10883737
TI  - Aggravation of chemically-induced injury in perfused rat liver by extracellular
      ATP.
AB  - The effects of purinergic receptor agonists on acute liver damage and
      hemodynamics were studied using chemically-induced liver injury. Rat livers were
      perfused in situ 24 h after treatment with D-galactosamine (800 mg/kg, i.p.). In
      these livers, infusion of ATP (50 microM) into the portal vein caused a rapid
      increase in the leakage of LDH and AST from perfused liver in a dose dependent
      manner, accompanied with flow reduction. The similar but less effective responses
      were also observed by the infusion of ADP. Infusion of adenosine, a P1-receptor
      agonist, induced only minimal changes of liver damage and flow rate. The ATP
      induced changes were almost completely suppressed by P2-receptor antagonist,
      suramin, but not affected by P1-receptor antagonist, 8-phenyltheophylline.
      Pretreatment of rats with gadolinium chloride, which depletes Kupffer cells, did
      not inhibit the potentiation of liver damage caused by ATP, whereas hemodynamic
      effects of ATP were significantly attenuated by gadolinium. These results
      indicate that extracellular ATP aggravates acute liver injury mediated by P2-type
      purinergic receptors.

PMID- 10883738
TI  - Carvedilol: a beta blocker with antioxidant property protects against gentamicin
      induced nephrotoxicity in rats.
AB  - Gentamicin is an antibiotic effective against gram negative infections, whose
      clinical use is limited by its nephrotoxicity. Since the pathogenesis of
      gentamicin-induced nephrotoxicity involves oxygen free radicals, the antioxidant
      carvedilol may protect against gentamicin-induced renal toxicity. We therefore
      tested this hypothesis using a rat model of gentamicin nephrotoxicity. Carvedilol
      (2 mg/kg) was administered intraperitoneally 3 days before and 8 days
      concurrently with gentamicin (80 mg/kg BW). Estimations of urine creatinine,
      glucose, blood urea, serum creatinine, plasma and kidney tissue malondialdehyde
      (MDA) were carried out, after the last dose of gentamicin. Kidneys were also
      examined for morphological changes. Gentamicin caused marked nephrotoxicity as
      evidenced by increase in blood urea, serum creatinine and decreased in creatinine
      clearance. Blood urea and serum creatinine was increased by 883% and 480%
      respectively with gentamicin compared to control. Carvedilol protected the rats
      from gentamicin induced nephrotoxicity. Rise in blood urea, serum creatinine and
      decrease in creatinine clearance was significantly prevented by carvedilol. There
      was 190% and 377% rise in plasma and kidney tissue MDA with gentamicin.
      Carvedilol prevented the gentamicin induced rise in both plasma and kidney tissue
      MDA. Kidney from gentamicin treated rats, histologically showed necrosis and
      desquamation of tubular epithelial cells in renal cortex, whereas it was very
      much comparable to control with carvedilol. In conclusion, carvedilol with its
      antioxidant property protected the rats from gentamicin-induced nephrotoxicity.

PMID- 10883739
TI  - Endothelin-1 release from the lamb ductus arteriosus: are carbon monoxide and
      nitric oxide regulatory agents?
AB  - We have proposed that endothelin-1 (ET-1), formed through the activation of a
      cytochrome P450 (CYP450)-based monooxygenase reaction, is important for
      generation of contractile tone in the ductus arteriosus and, consequently, for
      closure of the vessel at birth. The present investigation was undertaken to
      ascertain, using an isolated ductus preparation from near-term fetal lambs,
      whether carbon monoxide (CO) and nitric oxide (NO) qualify as regulators of the
      CYP450/ET-1 system. Preparations released ET-1 at rest and its amount showed no
      significant reduction following removal of the endothelium. Basal release was not
      changed by the NO synthesis inhibitor, N(G)-nitro-L-arginine methylester (L-NAME,
      100 microM), nor by agents altering cyclic GMP content (i.e. increase; ONO-1505,
      1 microM) and action (i.e. decrease; LY-83583, 10 microM). These findings extend
      previous work showing no effect of the CO synthesis inhibitor zinc protoporphyrin
      IX (ZnPP, 10 microM) under the same conditions (10). Conversely, both CO (65
      microM) and the NO donor, sodium nitroprusside (SNP, 10 microM), curtailed ET-1
      release. ET-1 release was increased by oxygen and reduced by pyrogens (endotoxin
      and IL-1, both at 100 ng mL(-1)). The endotoxin effect tended to be reversed by L
      NAME and ZnPP, used singly or in combination. We conclude that ET-1 is formed
      naturally in the ductus and that its formation may change in response to
      physiological (oxygen) and pathophysiological (pyrogens) stimuli. Endogenous CO
      and NO, however, appear to have little or no role as ET-1 regulators.

PMID- 10883740
TI  - New considerations about measuring airway hyperresponsiveness.
AB  - Measuring airway responsiveness to inhaled bronchoconstrictor stimuli, such as
      methacholine or histamine, has become an important tool in the diagnosis of
      asthma. This is measured by patients inhaling increasing doses or concentrations
      of the bronchoconstrictor stimulus until a given level of bronchoconstriction is
      achieved. Inhaled allergens initiate processes that increase airway inflammation
      and enhance airway hyperresponsiveness in asthmatic subjects. Studies using
      inhaled allergen challenges have provided insight into how changes in airway
      hyperresponsiveness are regulated by induced inflammatory processes. These
      changes in airway hyperresponsiveness (1-2 doubling doses) have been shown to be
      of much smaller magnitude than those demonstrated when asthmatics with stable
      airway hyperresponsiveness are compared to normals (4-8 doubling doses). These
      allergen-induced changes would be of little relevance in subjects with normal
      airway responsiveness, because they would not increase the degree of airway
      responsiveness into the asthmatic range. They are, however, important in
      asthmatics who already have airway hyperresponsiveness because they are similar
      to changes associated with worsening asthma control. It is likely that the
      mechanisms responsible for the changes in airway hyperresponsiveness following
      experimental allergen exposure are similar to those producing transient worsening
      of control in asthmatics. Nevertheless, it is unlikely that the mechanisms of the
      transient allergen-induced airway hyperresponsiveness will explain the underlying
      mechanisms of the persistent airway hyperresponsiveness in asthmatic patients
      when compared with normal individuals.

PMID- 10883741
TI  - The placebo effect in asthma drug therapy trials: a meta-analysis.
AB  - A meta-analysis of randomized controlled asthma drug therapy trials published in
      the English literature from January 1991 to June 1995 was performed to estimate
      the magnitude and direction of the placebo effect in stable ambulatory asthmatic
      patients. Among placebo groups, the mean absolute increase in forced expiratory
      volume in 1 sec (FEV1), weighted for sample size and variance, was 0.11 L/min,
      and the mean percent increase in FEV1 was 4.81%. The corresponding placebo group
      changes in peak expiratory flow (PEF) were in an opposite direction to those of
      FEV1; there was a mean absolute decrease of 2.24 L/min, and a mean percent
      decrease of 4.21%. Changes for active treatment groups were greater in magnitude.
      However, there were no statistically significant differences in mean changes
      comparing the placebo groups to the treatment groups, for any of the outcome
      measures. Mean increases in PEF and FEV1 exceeded 10% in 5 of 33 placebo groups,
      as compared to 13 of 33 active treatment groups. In conclusion, in well-designed
      long-term drug therapy studies in stable asthmatics the pooled placebo effect is
      small but measurable, with FEV1 and PEF showing different directions of response.
      Moreover, a modest number of patients receiving placebo have changes in pulmonary
      function that might be interpreted as clinically significant.

PMID- 10883742
TI  - Dose-response evaluation of levalbuterol versus racemic albuterol in patients
      with asthma.
AB  - Albuterol, in all marketed forms, is sold as a racemate, composed of a 50:50
      mixture of (R)- and (S)-isomers. Racemic albuterol and the single isomer version
      (R)-albuterol (levalbuterol) were compared in a randomized, double-blind, dose
      ranging five-way crossover study in patients (n = 20) with mild persistent to
      moderate persistent asthma. Placebo, racemic albuterol (2.50 mg), or levalbuterol
      (0.31, 0.63, or 1.25 mg) were delivered as single, nebulized doses to 5 male and
      15 female nonsmoking patients with asthma aged 18-50 years. Serial pulmonary
      function was assessed at 15-min intervals and mean time to onset of activity and
      duration of improvement of forced expiratory volume in 1 sec (FEV1) were
      measured. In addition, blood chemistries, electrocardiogram (ECG) readings, and
      patient subjective assessment of adverse symptoms were recorded. Levalbuterol was
      found to provide significant bronchodilatory activity and was well tolerated.
      Levalbuterol 1.25 mg provided the greatest increase and duration in FEV1
      improvement, whereas racemic albuterol (2.50 mg) and levalbuterol 0.63 mg
      provided comparable effects. The lower doses of levalbuterol were associated with
      a less marked effect on heart rate and potassium than racemic albuterol or high
      dose levalbuterol. These data suggest that 0.63 mg levalbuterol provides
      bronchodilation equivalent to 2.50 mg racemic albuterol with less beta-mediated
      side effects.

PMID- 10883743
TI  - Heat-killed Mycobacterium bovis-bacillus Calmette Guerin-suppressed total serum
      IgE response in ovalbumin-sensitized newborn mice.
AB  - To determine the impact of bacillus Calmette Guerin (BCG) vaccination on IgE
      production in ovalbumin (OVA)-sensitized newborn mice, four groups (I, II, III,
      IV) of BALB/c mice were immunized on the first day of life with live BCG, killed
      BCG, BCG diluent, and saline, respectively. No injection was applied to mice in
      group V (control). All mice except group V were sensitized and challenged with
      OVA in the fourth and sixth weeks, respectively, and serum total IgE levels were
      determined at 8 weeks, 2 weeks after the second OVA challenge. IgE levels of all
      groups were significantly higher than the control group except for group II (p =
      0.95). Mice in group II showed significantly lower IgE values than group IV and I
      (p = 0.007 and p = 0.003, respectively). We concluded that heat-killed BCG may
      downregulate IgE response to OVA in newborn mice.

PMID- 10883744
TI  - Assessment of psychological factors associated with adherence to medication
      regimens among adult patients with asthma.
AB  - Nonadherence with asthma medications is a significant problem associated with
      unnecessary functional limitations. The development of measures to assess
      psychological factors important to adherence with medication regimens among adult
      patients with asthma is described in the present report. The results indicated
      that the reliability and validity of the newly designed measures were adequate.
      Patients that did not perceive a need to take their medications as prescribed or
      those already taking their medications as prescribed had better pulmonary
      function. The results are discussed in terms of their implications for future
      studies, such as motivational interventions to enhance adherence with asthma
      medications.

PMID- 10883745
TI  - Study of the prevalence of asthma in adults in North India using a standardized
      field questionnaire.
AB  - Prevalence of asthma was calculated using a Hindi adaptation of the International
      Union Against Tuberculosis and Lung Disease (IUATLD)-1984 questionnaire. The
      questionnaire was administered to patients with and without asthma to select
      specific items to define asthma. Questionnaire validity was tested against
      physician-diagnosed asthma in 753 individuals in the field, with sensitivity and
      specificity of 63.1% and 98.8%, respectively. The field prevalence study was
      conducted among 958 men and 1158 women. True population prevalence, calculated
      from the observed prevalence using specificity and sensitivity of the
      questionnaire, was 3.94% in urban men, 3.99% in rural men, and 1.27% in both
      urban and rural women.

PMID- 10883746
TI  - Urbanization and the risk of asthma among schoolchildren in the Palestinian
      Authority.
AB  - The aim of the present survey was to compare the prevalence of symptoms
      suggestive of asthma in boys and girls aged 6-7 and 13-14 years in a rural and an
      urban area in the West Bank. For this purpose, the International Study of Asthma
      and Allergies in Childhood (ISAAC) questionnaire was issued to 970 schoolchildren
      in the two regions. The response rate was 92.2%. The prevalences of ever wheezing
      in the urban and rural areas were 16.4% and 12.0%, respectively (p < 0.05); the
      12-month prevalences of wheezing were 10.5% and 5.5%, respectively (p < 0.05);
      the prevalences of more severe wheeze were 4.5% and 1.7%, respectively (p <
      0.05); and prevalences of diagnosed asthma were 4.2% and 2.8%, respectively (p =
      NS). When controlling for age by stratification, the significant association
      between prevalence rates and place of residence persisted in the 13-14-year age
      group. These results also show that the prevalence of asthma among Palestinian
      children is moderately high in comparison with that reported from developing
      countries, but lower than those reported from Western countries. This survey, the
      first epidemiological survey on asthma in the West Bank, demonstrates a marked
      difference between urban and rural areas. The findings emphasize the need for
      further study of the environmental determinants of the disease among Palestinian
      children.

PMID- 10883748
TI  - Bronchial sensitivity to histamine in former asthmatics: redevelopment of
      symptoms during a year of followup.
AB  - The aim of this protocol was to study bronchial responsiveness in 23 former
      asthmatics who were free of symptoms for at least 5 years. Bronchial
      hyperreactivity (BHR) was evaluated with histamine challenge test and the results
      were compared with those of 20 normal subjects and 20 current asthmatic patients.
      Among the former asthmatics 65% fulfilled the criteria of BHR. During 1 year of
      followup, two former asthmatics redeveloped asthma symptoms. Interestingly, one
      patient had no BHR when initially tested. These findings suggest that the absence
      of BHR does not guarantee the nonrecurrence of asthma symptoms in former
      asthmatics.

PMID- 10883747
TI  - Chronic effects of inhaled albuterol on beta-adrenoceptor system function in
      human respiratory cells.
AB  - The in vivo effects of beta-adrenergic receptor (betaAR) agonists given
      chronically by metered-dose inhaler (MDI) on the molecular components of the beta
      adrenoceptor system expressed by human respiratory cells are poorly understood.
      This study examined the effects of inhaled albuterol (180 microg four times daily
      for 7 days) on betaAR function of airway epithelial cells (AECs) and alveolar
      macrophages (AMs) freshly isolated from 10 normal subjects. Responses were
      related to beta2AR genotype in codons 16 and 27, regions which affect chronic
      responses to beta2-agonists. In AEC, betaAR density and adenosine cyclic 3',5'
      phosphate (cAMP) production in response to isoproterenol (ISO) were significantly
      lower in the albuterol versus placebo treatment arm (p < 0.01 for both).
      Moreover, in AEC, albuterol treatment increased betaAR-kinase (betaARK) protein
      immunoreactivity. In contrast, in AM, albuterol tended to decrease betaAR density
      and cAMP production but changes did not achieve statistical significance (p >
      0.20 for both) and had no effect on betaARK immunoreactivity. Changes in betaAR
      density occurred in all subjects but tended to be greater in subjects with the
      glycine 16 genotype. In cultured cells exposed to equal concentrations of beta
      agonist in vitro, the magnitude of betaAR down-regulation (p < 0.05) and cAMP
      densensitization (p < 0.05) was greater in AEC than AM. These results indicate
      that albuterol taken by inhalation in a therapeutically relevant dose for 1 week
      produces betaAR down-regulation, densensitizes the cAMP response of airway
      epithelial cells to a beta2-adrenergic agonist, and increases betaARK
      immunoreactivity. Greater densensitization of AEC than AM in response to chronic
      albuterol inhalation likely reflects cell type-specific responses.

PMID- 10883749
TI  - Kinesthetic and visual image in modeling closed motor skills: the example of the
      tennis serve.
AB  - It was assumed that kinesthetic modeling has more beneficial effects on learning
      the tennis serve than visual modeling because the spatial anchor points used to
      reach targets within the vicinity of the body are mainly defined with respect to
      the body. Also, we predicted that the efficiency of modeling is also affected by
      the way the representations are activated mentally. Thirty two participants were
      assigned to kinesthetic or visual modeling with or without mental practice.
      Analyses showed the primacy of kinesthetic representation over visual
      representation in terms of speed scores and form performances but only if the
      learner had the opportunity to rehearse the model mentally. The results support
      the contention that the motor system can program closed skills more easily when
      one can represent efficiently the kinesthetic image of its later execution.

PMID- 10883750
TI  - Depression in early adolescence: relation to externalising and internalising
      behaviour.
AB  - The relationship between depression, on the one hand, and externalising and
      internalising behaviour, on the other, in 151 adolescents (79 boys and 72 girls)
      was examined with respect to the possible moderating role of sex-role
      stereotyping. The Reynolds Adolescent Depression Scale, the Achenbach Teacher
      Report Form, and the Australian Sex-Role Scale were used to assess the hypothesis
      that adolescents adapt to the experience of depression in gender-appropriate
      ways. A regression analysis indicated that the pattern of relationships was
      different for boys and girls. The hypothesis was supported for boys and
      externalising behaviour but not for girls and internalising behaviour.

PMID- 10883751
TI  - Interaction of psychological type and anxiety sensitivity on academic
      achievement.
AB  - The Myers-Briggs Type Indicator and the Anxiety Sensitivity Index were
      administered to 143 undergraduate college students. Analyses of variance were
      performed to assess the relationship between these indices and semester grades
      (Grade Point Average). The Myers-Briggs Sensing-Intuitive and Judging-Perceiving
      dimensions showed significant main effects on GPA. The interaction of Judging
      Perceiving and Anxiety Sensitivity was also significant (F = 18.00, p<.0001),
      although that of Sensing-Intuition and Anxiety Sensitivity was not (F = 3.51,
      p=.06). These findings suggest that personality factors measured by the Myers
      Briggs Type Indicator may serve as mediating variables in evaluating whether
      trait anxiety has a facilitating or debilitating effect on academic achievement.

PMID- 10883752
TI  - Comment on Birgegard and Sohlberg's (1999) suggestions for research in subliminal
      psychodynamic activation.
AB  - Methodological changes in subliminal psychodynamic activation experiments based
      on the assumption that multiletter messages can be encoded automatically
      (Birgegard & Sohlberg, 1999) are questioned. Their contention that partial
      experimental messages and appropriate nonsense anagram controls (Fudin, 1986)
      need not be presented in every experiment is supported, with a reservation. If
      the difference between responses to the complete message and its control is
      significant in the predicted direction, then Fudin's procedure should be used. A
      nonsignificant difference between the response to each partial message and its
      control is needed to support the assumption of proponents of subliminal
      psychodynamic activation that successful outcomes are effected by the encoding of
      the meaning of a complete message. Experiments in subliminal psychodynamic
      activation can be improved if their methodologies take into account variables
      that may operate when subliminal stimuli are presented and encoded.

PMID- 10883753
TI  - A broad range of forces is encompassed by the maximum manual muscle test grade of
      five.
AB  - This retrospective study summarizes the range of knee extension forces associated
      with the manual muscle test grade of 5. The range of the forces (>560 Newtons)
      was large and encompassing of more than 86% of measurable forces. These findings
      help to explain the insensitivity of manual muscle testing and why it has such a
      profound ceiling effect.

PMID- 10883754
TI  - Self-confidence, self-esteem, and assumption of sex role in young men and women.
AB  - This study investigated the use of the English translation of a paper-and-pencil
      self-confidence scale developed in French by Garant, Charest, Alain, and
      Thomassin in 1995. The translated self-confidence scale measured self-confidence,
      or the belief that one will succeed at whatever one undertakes, as distinct from
      self-esteem or the feeling that one is a worthwhile person. Unlike a number of
      previous studies. there was no sex difference in self-confidence favoring men:
      however, scores on the masculinity portion of Bem's Sex role Inventory (1974)
      were highly correlated with self-confidence for both men (r=.59) and women
      (r=.69).

PMID- 10883755
TI  - Ability profile of the elite volleyball player.
AB  - The aim of this study was to examine the cognitive, motor, and perceptual
      abilities of elite volleyball players. These abilities were considered
      responsible for high quality performance by expert athletes. The elite group was
      formed with 12 members of the Greek Junior National Volleyball team. A group of
      18 physical education students were the novice athletes. The measured abilities
      were selected by expert volleyball coaches as those most important for an elite
      athlete. Analysis showed differences between the abilities of the two groups of
      athletes were significant. An ability profile for the elite volleyball player can
      be formed.

PMID- 10883756
TI  - A Dutch version of the Social Support for Exercise Behaviors Scale.
AB  - We studied the reliability of a Dutch version of the Social Support for Exercise
      Behaviors Scale, originally developed by Sallis, Grossman, Pinski, Patterson, and
      Nader, using a sample of 461 older adults between 55 and 65 years of age.
      Cronbach alpha for the three subscales was calculated, respectively, as .69, .71,
      and .26, which are lower than the alphas reported in the original study. This may
      be due to the cultural differences between The Netherlands and the United States
      and differences between the samples of the two studies.

PMID- 10883757
TI  - Feeling-of-knowing judgments and strategy selection in spelling.
AB  - Metacognitive processes, such as monitoring one's knowledge and selecting
      appropriate strategies, may be important in skilled spelling. We hypothesized
      that skilled spellers have knowledge of which words they know how to spell and
      also that the accuracy with which people monitor their knowledge should be
      related to the spelling strategies they select. College students provided Feeling
      of-Knowing ratings about the spellings of words and also spelled the same words
      and indicated whether they sounded out or remembered the spellings. Feeling-of
      Knowing ratings were moderately correlated with Spelling Accuracy and were more
      strongly predictive of Spelling Accuracy when Feeling-of-Knowing ratings and
      spellings were done as part of the same task rather than as separate tasks.
      Analyses indicate that those who were better at monitoring their knowledge of
      spelling also chose more congruent spelling strategies. The results suggest that
      skilled spellers can monitor which words they know how to spell, but this ability
      to monitor is far from perfect and varies considerably. Further, the results
      suggest that ability to monitor spelling knowledge is related to strategy
      selection in spelling.

PMID- 10883758
TI  - Temporal changes in the excitability of the reciprocal inhibitory interneurones
      preceding cocontraction of the antagonistic muscle in the human wrist.
AB  - The supraspinal control of reciprocal inhibitory interneurones preceding
      cocontraction of antagonistic muscles in the human wrist was investigated in 5
      subjects. The method combined a reaction time task paradigm and a technique for
      conditioning the H-reflex. Unconditioned H-reflexes were elicited from flexor
      carpi radialis (FCR) and extensor carpi radialis (ECR) muscles by using
      electrical stimulation to median and radial nerves. The conditioned H-reflex of
      the FCR muscle was obtained by simultaneous electrical stimulation to the median
      and the radial nerves. While subjects performed the bilateral isometric
      cocontraction task, excitabilities of the alpha motoneurone pools and that of the
      reciprocal inhibitory interneurones were assessed by the unconditioned and
      conditioned H-reflex, respectively. Alpha mononeuron pools of FCR and ECR muscles
      were facilitated starting from approximately 50 msec. preceeding EMG activities.
      Reciprocal inhibitory interneurones which suppressed FCR alpha motoneurones were
      disinhibited at almost same time. The present results suggested that supraspinal
      control of the reciprocal inhibitory interneurones preceding antagonist
      cocontraction is different from that of preceding agonist contraction.

PMID- 10883759
TI  - Object recognition may distort size perception.
AB  - Size estimation may be influenced by characteristics recalled about the object
      viewed. This study evaluated the influence of object familiarity on estimation of
      size. We compared size estimates of several familiar objects with size estimates
      of undefined objects matched for dimensions of pattern and color. Those
      estimating the size of the familiar objects made significantly larger errors than
      those estimating the size of the undefined objects. In a second study size
      estimation errors from memory were larger than when objects were directly viewed.
      Experience with the objects appears to decrease accuracy of estimates of size but
      errors may be reduced by directly observing the object.

PMID- 10883760
TI  - Feedback regarding goal achievement and intrinsic motivation.
AB  - The aim of the present study was to examine the effect of feedback for
      achievement of a goal on intrinsic motivation. Analysis showed that positive feed
      back enhanced perceptions of competence while negative feedback lowered these.
      Neither condition, however, influenced intrinsic motivation.

PMID- 10883761
TI  - Goal orientation and ratings of perceived exertion in graded exercise testing of
      adolescents.
AB  - This study examined the relationship between adolescents' goal orientation in
      sport and their ratings of perceived exertion (RPE) during a graded exercise
      test. Subjects (N = 114; 56 boys) were randomly selected adolescents (ages 11 to
      15 years) who were part of a 5-year longitudinal study of cardiac growth. RPE was
      measured during each of three submaximal stages throughout the graded exercise
      test and again during the maximal stage. A series of regression analyses showed
      that RPE for female subjects was significantly predicted by Task Orientation,
      Perceived Ability, and Intensity of Leisure Activity at Stage 1, Task Orientation
      and Perceived Ability at Stage 2, and by Intensity of Leisure Activity at Stage
      3. Examination of the beta weights indicated that lower RPE for the girls was
      related to higher Task Orientation and lower Perceived Ability and more
      experience with higher Intensity of Leisure Activity. Results are discussed in
      light of the literature pertaining to goal orientation and ratings of perceived
      exertion.

PMID- 10883762
TI  - Normative and validation studies of the Nine-hole Peg Test with children.
AB  - This study evaluated norms for fine motor dexterity skills on elementary school
      children of ages 5 through 10 and conducted reliability and validity stud ies
      utilizing the Nine-hole Peg Test. The sample included 826 students in 10
      elementary schools. Moderately high test-retest reliability (rs = .81 and .79)
      and high interrater agreement (rs > .99) were obtained. Older students had
      shorter completion time that measured fine motor dexterity than younger students.
      Significant sex differences were found in completion time, but only for the
      dominant hand. Correlations of -.80 and -.74 between the scores on the Nine hole
      Peg Test and Purdue Pegboard Test at all tested ages indicated adequate
      concurrent validity of the measures and a significant difference in test scores
      between regular and special education groups provided further evidence of
      construct validity. The findings supported the Nine-hole Peg Test as an effective
      screening tool for fine motor dexterity of school-age children.

PMID- 10883763
TI  - Continuity between waking life and dreaming: are all waking activities reflected
      equally often in dreams?
AB  - The present study investigated the frequency of cognitive activities such as
      writing, reading, and using a computer in comparison to activities like walking
      or talking with friends. Analysis indicated that focused thinking activity occurs
      rarely in dreams. The findings, thus, are consistent with the theory which holds
      that dreams reflect emotional concerns of the dreamer.

PMID- 10883764
TI  - Predicting anxiety in competitive sports.
AB  - The relationship between attitudes toward winning and competitive anxiety was
      explored in 59 undergraduate students competing on four different New Jersey
      based, NCAA Division III sports teams. In a backward multiple regression
      analysis, cognitive anxiety was predicted significantly only by self-confidence,
      while somatic anxiety was predicted significantly by self-confidence and the
      rated importance of the competition.

PMID- 10883765
TI  - Analysis of body esteem in female college athletes and nonathletes.
AB  - This research compared the scores on the three subscales of the Body Esteem Scale
      of 67 female intercollegiate athletes from various sports, and 57 female
      nonathlete college students enrolled in regular college classes. Analysis
      indicated no significant differences between the groups on the Sexual
      Attractiveness and Weight Concern subscales, but only on the Physical Condition
      subscale, with athletes reporting higher scores and more positive perceptions of
      body esteem than nonathletes.

PMID- 10883766
TI  - Judgments of emotion by nurses and students given double-bind information on a
      patient's tone of voice and message content.
AB  - We examined the communication process in a situation typical of the nursing
      setting by use of a double-bind communication. Our objective was to examine which
      of two cues in communications from a patient, tone of voice or verbal content,
      was more important in judging the speaker's emotional status and personality
      traits and in arousing the listening nurse's emotions. Subjects were 82 nurses
      who worked at the university hospital and 100 students who were studying at the
      Faculty of Nursing of the university. They were assigned into four groups at
      random, presented professionally tape-recorded scripts representing a patient's
      verbal report, and then completed a questionnaire concerning the speaker's
      emotional status as well as the listener's own emotional status. When the
      listeners judged the speaker's emotional status, they gave more attention to a
      negative emotional expression, and when the listeners formed an impression of the
      speaker's personality traits, they were influenced by the speaker's tone of voice
      rather than by the content of the speech.

PMID- 10883767
TI  - Angles of shadows as cues for judging the distance of shadow casting objects.
AB  - 40 participants were presented the six possible comparisons of four pictures of
      cylinders and their shadows. For each comparison, each participant was to decide
      which cylinder was most distant from a reference point. Overall 15 of the
      participants got all six judgments correct, an outcome that is exceedingly
      unlikely by chance.

PMID- 10883768
TI  - Cognitive learning strategies: their effectiveness in acquiring racquetball
      skill.
AB  - Racquetball players were compared to assess whether a Self-directed strategy
      (self-monitoring), a Task-oriented strategy (attentional focusing), or a Combined
      use of both strategies would be beneficial in acquisition of racquetball skills.
      According to skill (Beginning, Advanced), players (N=80) were assigned into
      treatment groups. After treatment, participants executed diagonal lob serves and
      rallies for Acquisition and Retention phases (Session 1). During Session 2,
      subjects competed in a modified play setting (Transfer phase). Analysis of
      variance with repeated measures showed differences by skill during the basic
      tests favored Advanced players. During modified play, the Task-oriented group won
      significantly more points and games compared to the Self-directed and Control
      groups, regardless of skill. Results are discussed relative to skill and the
      literature on learning strategies.

PMID- 10883769
TI  - Performance of children with and without learning disabilities on Canter's
      Background Interference Procedure and Koppitz's scoring system for the Bender
      test.
AB  - Performance of 66 children, 30 with and 36 without learning disabilities, in four
      ways using the Bender Visual-motor Gestalt Test was compared. First, the test
      with the standard Koppitz scoring procedure, second with the Canter Background
      Interference Procedure sheet using the standard Koppitz scoring procedure; third,
      the Bender test on a standard sheet of paper using Canter scoring procedure; and
      fourth, the Canter Background Interference Procedure (BIP) sheet using the Canter
      scoring procedure. The effectiveness of the Canter procedure was examined when
      scored with an age-appropriate normative scoring system. This was accomplished by
      combining the Canter BIP interference sheet with the Koppitz scoring system. The
      children ranged in age from 6 to 10 years. Using discriminant analysis, all four
      methods correctly categorized statistically significant percentages of both types
      of students but there was a significant difference on the Canter BIP sheet using
      the Canter scoring procedure. This procedure classified students with the least
      absolute number and percentage of either false negatives or false positives when
      compared with the other three methods, suggesting that using this scoring method
      with the Bender Gestalt may be better for identifying younger children with
      learning disabilities.

PMID- 10883770
TI  - When academic performance is higher than WISC-III IQs, is the sequential
      processing model of intelligence the preferred approach to assessment?
AB  - The WISC-III is probably the most widely used measure of intelligence for
      children of school age. On occasion, an unusual psychometric profile emerges in
      which academic ability is much higher than would be expected for IQ. Initial data
      for 8 children suggest that the sequential-processing model of intelligence may
      be the preferred approach to assessment in such situations.

PMID- 10883771
TI  - Perception of current and ideal body size in preschool age children.
AB  - 25 girls and 25 boys between the ages of 5 and 7 years indicated their current
      and desired body size on Collins' figures. The children's weight and height were
      measured, and the Body Mass Index was calculated. 52% of girls and 44% of boys
      expressed a wish to become thinner in relation to perception of their own body.
      Significant sex differences were found in selection of the ideal figure: girls
      showed greater preferences for a thinner figure than boys. There was a
      significant correlation between perception of current figure and Body Mass Index
      for boys but not for girls.

PMID- 10883772
TI  - Automaticity, spelling, and second language learning.
AB  - This study investigated the relationship between a chronometric estimate of
      automaticity for the spelling of French words (Automaticity) and performance on
      four tests of French language attainment among a sample of Year 11 students of
      French as a foreign language. Fifty participants each completed a computerized
      test of French spelling and attainment tests in four aspects of French language
      learning: reading comprehension, writing fluency, oral fluency, and aural
      comprehension. Correlations were significant between Automaticity and performance
      on all four tests of French language attainment as well as on overall attainment.

PMID- 10883773
TI  - Delayed left ear accuracy during childhood and early adolescence as indicated by
      Roberts' Dichotic Word Listening Test.
AB  - A total of 200 girls and boys between the ages of 6 years and 15 years were
      administered Roberts' Dichotic Word Listening Test. A statistically significant
      relatively abrupt and maintained increase in left ear accuracy was noted after 9
      years of age (eta = .55). Except for a mild improvement after 6 to 7 years of
      age, comparable changes were not observed for the right ear. The magnitude of the
      effect was not significantly diminished even after covariance for verbal fluency
      and semantic categorization. These results are compatible with the observations
      that myelination of the cerebral commissures and electroencephalographic phase
      relations of the right hemisphere achieve near-adult characteristics after 9
      years of age. Boys displayed less accuracy for dichotic word listening,
      particularly for the left ear, compared to the girls eta = .20).

PMID- 10883774
TI  - Perceived electrosensitivity and magical ideation.
AB  - We report, in 40 healthy right-handed men, an association between perceived
      sensitivity to weak electromagnetic fields and scores on the Magical Ideation
      scale, assessing experience of and beliefs in forms of causation that are
      nonexistent according to current scientific standards (r = .48, p =.002). Based
      on our previous research, we interpret this finding as reflecting human subjects'
      propensity to assume connections between own organismic state and (objectively
      unrelated) environmental variables. We emphasize, however, the need for studies
      which directly assess accuracy in detection of electromagnetic fields as a
      function of self-rated electrosensitivity.

PMID- 10883775
TI  - Temporal stability of the Learning Efficiency Test-II for adults.
AB  - This study examined the temporal stability of the Learning Efficiency Test-II
      with 101 undergraduate students over a mean test-retest time interval of 19 days.
      Temporal stability estimates were .79 for the Visual Modality factor score, .75
      for the Auditory Modality factor score, and .80 for the Global Memory factor
      score. A repeated measures analysis of variance for these three factor scores
      indicated no significant mean differences from Test 1 to Test 2. Slightly lower
      retest correlations were obtained for each of the 12 subtests, with correlations
      ranging from .44 to .70. The findings indicate that some subtests are reliable to
      assess the memory processing of adults over time and also highlight the stability
      over 19 days of memory processes for intact learners. Other studies with older
      groups of persons are needed to examine the stability of scores.

PMID- 10883776
TI  - Proneness to eating disorders: weightlifters compared to exercisers.
AB  - Previous findings were confirmed suggesting that weightlifters may be more prone
      to eating disorders than are casual exercisers. 25 weightlifters' mean eating
      disorder score was significantly higher than that of 25 casual exercisers when
      contrasted for practical difference.

PMID- 10883777
TI  - Perceptions of parents' support for learning: the influence of sibship size.
AB  - Marjoribanks in 1989 and Marjoribanks and Kwok in 1998 examined relationships
      among social status, sibship size, and measures of parents' support for learning
      for adolescents in Australia and Hong Kong, respectively. This present study
      investigated similar relationships for 1,305 (700 females, 605 males) 18 yr. old
      African students in South Africa. The findings from the three cross-cultural
      investigations suggest a sibling hypothesis which states that, after taking into
      account family social status, sibship size has modest significant inverse
      associations with females', but not with males', perceptions of their parents'
      support for learning. These studies indicate that in large families, parents may
      provide fewer resources for daughters than for sons. The results may help explain
      a small part of the sex-related differences that occur in students' affective and
      academic school outcomes.

PMID- 10883778
TI  - Mood state changes of students enrolled in physical activity classes.
AB  - 74 students enrolled in physical activity classes completed the happiness and
      sadness scales of the Emotional Assessment Scale each week for the 7-week course.
      A repeated measures analysis of variance indicated no significant change in mean
      mood state scores. Subjects' scores remained fairly happy throughout the length
      of the course, women having significantly happier scores than men.

PMID- 10883779
TI  - Consistency of hand use and frequency of colds among college students.
AB  - The self reported annual frequencies of colds were assessed for two groups of 37
      students each who were either consistent or inconsistent in the use of their
      hands. These data indicated that the inconsistent hand use group reported
      significantly more colds than their consistent hand use peers.

PMID- 10883780
TI  - Misuse of multivariate analysis of variance in behavioral research: the fallacy
      of the "protected" F test.
AB  - Researchers who examine multiple outcome variables sometimes invoke a
      multivariate analysis of variance approach known as the "protected F test" to
      control for experimentwise Type I error rate. Unfortunately, this procedure
      affords protection against experimentwise Type I error only in rare instances.
      The purpose of the present paper is to present the case against the protected F
      test and to discuss alternative methods of controlling for Type I error,
      including the Bonferroni adjustment and descriptive discriminant analysis. The
      latter approach is briefly elaborated as a truly multivariate solution for
      multivariate phenomena. The author cites multiple examples of proper and improper
      use of multivariate analysis of variance in research on child development.

PMID- 10883781
TI  - Comprehension and production of gestures by children with normal and impaired
      language at ages 4, 5, and 6.
AB  - 12 children with normal verbal language, ages 4, 5, and 6, were matched with 12
      children with impaired verbal language. When the two groups were compared for
      comprehension and production of nonverbal gestures as well as verbal language,
      the latter group scored more poorly in both areas. Implications for speech
      language pathologists and other professionals in the assessment and remediation
      of language in language-impaired children are mentioned.

PMID- 10883782
TI  - Old and new scales for the assessment of body image.
AB  - Two new carefully constructed figure rating scales showed no greater validity
      than did the first such scale to be developed, as determined by the correlation
      between scale scores and body mass index and body weight.

PMID- 10883783
TI  - Those who hesitate lose: the relationship between assertiveness and response
      latency.
AB  - Individuals who are low in assertiveness may take longer to sort out, process,
      and state their own perceptions, attitudes and priorities, which puts them at a
      disadvantage in getting their needs met. The reason for this may not be
      inhibition in social situations or cognitive ability, but a lack of clarity
      regarding their own attitudes, opinions, preferences, goals, and priorities. 101
      undergraduate students (57% women and 43% men) completed a demographics
      questionnaire, the Wonderlic Personnel Test, a self-monitoring scale, the Marlowe
      Crowne Social Desirability Scale, the Rosenberg Self-esteem Scale, the College
      Self-expression Scale, and a test of the false-consensus effect. Response
      latencies to questions were measured. Individuals with higher scores on the
      Wonderlic Personnel Test answered items more quickly but, even when cognitive
      ability was controlled, individuals low in assertiveness still took significantly
      longer to respond to questions about themselves, their opinions, and their
      preferences. If individuals fall behind at this early step in the process of
      asserting themselves, then they may be more likely to miss opportunities to be
      assertive.

PMID- 10883784
TI  - On the origins of human laterality: environmental and hereditary variables in a
      sample of children.
AB  - On the basis of operationally defined handedness data from 1,348 subjects of both
      sexes and of ages 10 to 15 years, laterality was compared with prehistorical data
      of handprints found in caves. It was hypothesized that the greater production of
      left handprints found in caves in comparison with current data should be ascribed
      to a nonestablished deviation of lefthanders towards righthandedness as
      environmental pressures in the distant past were lower.

PMID- 10883785
TI  - The repeatability of choku-tsuki and oi-tsuki in traditional Shotokan karate: a
      morphological three-dimensional analysis.
AB  - The aim of the study was to quantify the repeatability of the displacement of
      selected body landmarks while performing two different basic karate attacks.
      Seven karateka (three men, four women) with different levels of training and
      knowledge of karate were filmed with an optoelectronic computerized instrument
      (sampling rate 100 Hz) that allows the three-dimensional reconstruction of the
      movements of selected body landmarks. Thirteen landmarks (head, hips, upper and
      lower limbs) were analyzed while performing 10 repetitions each of choku-tsuki
      (straight punch) and oi-tsuki (lunge punch). For each karateka and punch, the
      average time of execution was calculated, and the standard deviations of each of
      the three spatial coordinates x, y, z were computed for each landmark. A total
      standard deviation of the single karateka and punch was also calculated. For all
      karateka, the execution of oi-tsuki took longer than the execution of choku
      tsuki. For both punches and almost all landmarks, the largest repeatability
      (smallest standard deviation) was found in the vertical direction, while the
      smallest was found in the anteroposterior direction (direction of movement). In
      all karateka, oi-tsuki had a total standard deviation about 3 to 6 times larger
      than that measured during the performance of choku-tsuki. On average, women had a
      larger repeatability than men. The method employed in the current study allowed
      the quantitative analysis of the repeatability of two basic attacks in Shotokan
      karate by using a landmark based approach. The method could offer valuable help
      to karateka during training indicating which parts of the body do not repeat a
      selected movement with sufficient accuracy, thus assisting in the achievement of
      the most correct body form.

PMID- 10883786
TI  - Left turning traffic procrastinators: another look.
AB  - Replication of an earlier study indicated operators of lead vehicles moved out
      more slowly when someone was waiting behind them, especially women driving vans.

PMID- 10883787
TI  - Fundus pigmentation and equiluminant moving phantoms.
AB  - Visual phantoms are a perceptual completion illusion wherein contours and
      surfaces are seen where none physically exist. The visibility of moving phantoms
      was measured with equiluminant and near equiluminant chromatic inducing gratings
      for observers having a fundus classified as either darkly or lightly pigmented.
      Phantom visibility was greatest for observers with a lightly compared to a darkly
      pigmented fundus with the two groups showing differences in visibility as a
      function of background luminance. The results are discussed relative to
      equiluminant stationary phantom findings and a proposed relationship between
      phantom visibility and magnocellular pathway activity.

PMID- 10883788
TI  - Influence of age, sex, and balance on mature skipping by children in grades K-8.
AB  - This study examined the contributions of age, sex, and balance on maturity of
      skipping by children in Grades K-8. The subjects were 379 boys and 337 girls
      (ages 4-14 years) enrolled in a medium-size school system in southeastern Maine.
      Each subject was individually assessed on skipping as well as static and dynamic
      balance. To assess the independent statistical contributions of age, sex, static
      balance, and dynamic balance within each grade, data were subjected to multiple
      regression analysis. Development of mature form in skipping was related to
      balance in two isolated but unaccountable instances.

PMID- 10883789
TI  - Analysis of breathing in the crawl as a function of skill and stroke
      characteristics.
AB  - The purpose of this study was to measure and compare the durations of exhalation
      (DE), inhalation (DI), and inhalatory apnea (DAI) expressed as percentage of
      stroke-cycle duration using two groups (more expert and less expert) of 6 front
      crawl swimmers each at near 100-m speed (high speed) and 800-m speed (low speed).
      Two breathing conditions were considered, breathing to the preferred side with
      and without a nose-clip. The relationships between stroking characteristics
      (swimming speed, stroke rate, and stroke length) and the three durations of
      breathing were examined as a function of skill and swimming speed. The data show
      that use of a nose-clip does not significantly change those measures. At high
      speed, the more expert group had a lower inhalation and a higher exhalation than
      the less expert group. The stroke rate correlated with speed .92 (p<.01) and was
      mainly associated with inhalation (r=-.78, p<.01). Inclusion of exhalation as a
      second variable improved significantly (p<.01) the accuracy of the regression up
      to .97. At low speed, the less expert had lower inhalatory apnea than the more
      expert. Stroke length correlated with speed .86 (p<.01) and was mainly associated
      with inhalatory apnea (r=.70, p<.05). At high speed, the more expert had a lower
      inhalation than at low speed, while durations of exhalation and inhalatory apnea
      did not vary significantly. On the contrary, the less expert had a lower
      exhalation and a higher inhalatory apnea, while duration of inhalation remained
      relatively unchanged. The present study shows that these durations and their
      relations to stroking characteristics could be considered significant indicators
      of skill in swimming.

PMID- 10883790
TI  - Test of the validity of the judged sensory ratio of 1:2.
AB  - Garner found that observers judged the sensory ratio of 1:2 invalidly; however,
      it is possible that in Garner's experiment judgments were influenced by the
      different sets of variable stimuli used for the test. This paper reports an
      experiment designed to test the validity of the judged sensory ratio of 1:2
      without using different sets of variable stimuli. Bipolar continua of brightness
      and darkness were used. Participants first adjusted a brightness so that it was
      the double of a standard brightness located between the middle and the black end
      of the brightness continuum and subsequently adjusted a brightness so that it was
      the double of this double (the quadruple of the original standard brightness), or
      adjusted a darkness so that it was the double of a standard darkness located
      between the middle and the white end of the darkness continuum and subsequently
      adjusted a darkness so that it was the double of this double (the quadruple of
      the original standard darkness). Participants reported quadruples of each
      standard even if such quadruples could not exist on the bipolar continuum. This
      confirms that participants judged the sensory ratio of 1:2 invalidly.

PMID- 10883791
TI  - Ability to coordinate exertion of force by the dominant hand: comparisons among
      university students and 65- to 78-year-old men and women.
AB  - The purposes of this study were to examine the characteristics of ability to
      coordinate exertion of force in 60 healthy older people (30 men, 30 women) from
      the viewpoint of sex differences and to compare their performance with those of
      60 healthy university students (30 men, 30 women). The test of ability to
      coordinate exertion of force was conducted by having the subject fit the exertion
      value of grip strength to a changing demand value appearing on the display of a
      personal computer (using a bar chart-description form). The changes in the demand
      value were tracked. The variable estimating ability to coordinate exertion of
      force was the total sum of the differences between demand and the produced grip
      strength induced by time lapses. The ability to coordinate exertion of force in
      the older subjects was inferior to that of the younger subjects, and large
      individual differences were observed. Unlike the younger subjects, the means of
      the ability to coordinate exertion of force of the older subjects significantly
      decreased between trials. The ability to coordinate exertion of force of the
      older women was significantly inferior to that of the older men, but the means of
      the measurements among three trials shows a similar tendency to decrease in both
      sexes.

PMID- 10883792
TI  - Motor dimension of visual mental image transformation processes.
AB  - This paper concerns the influence of perceptual motor skills on the
      transformation processes during mental visual imaging. We first administered a
      visual recognition task to subjects, during which they scanned and rotated visual
      mental images. Then, we measured motor skills in perceptual situations. The main
      result is that both mental scanning and mental rotation processes are quicker
      when they simulate a perceptual motor skill of the subject. Furthermore, mental
      rotation seems to be canceled when the hemisphere activated by perception has to
      control the behavioral response. These results suggest that visual mental images
      are transformed partly via motor processes.

PMID- 10883793
TI  - Decrease in serum cortisol during yoga exercise is correlated with alpha wave
      activation.
AB  - We examined changes in brain waves and blood levels of serum cortisol during yoga
      exercise in 7 yoga instructors and found that alpha waves increased and serum
      cortisol decreased. These two measures were negatively correlated (r = -.83).
      Comparison with a control group of nonpractitioners is desirable.

PMID- 10883794
TI  - Influences of occlusion, color, and luminance on the perception of fragmented
      pictures.
AB  - The contribution of the magnocellular (M) pathway to perceptual completion and
      depth processing was examined by comparing performance under black-and-white
      conditions with isoluminant color and diffuse red background conditions expected
      to suppress M pathway activity. Participants identified the repeated figure in
      pictures where only fragments of the figures were visible. The fragments were
      presented either alone (unoccluded) or with an occluder (occluded) filling the
      space between them. Identification with an occluder involved amodally completing
      the fragments behind it, i.e., depth processing. All unoccluded versions were
      easy to identify indicating perceptual completion of the fragments was not
      influenced by suppressing M pathway activity. Black-and-white occluded versions
      were also easy to identify. The significantly longer identification times for
      occluded versions under isoluminant and diffuse red background conditions
      indicates amodal completion of the fragments was hindered when M pathway activity
      was reduced, supporting the importance of M pathway activity for depth
      processing.

PMID- 10883795
TI  - Are pain tolerance of female runners and use of pain coping strategies related to
      the experience of childbirth?
AB  - Experimental ischaemic pain tolerances were compared for 10 female runners who
      had given birth and 10 female runners who had not given birth. In both groups
      pain tolerances were positively correlated with the spontaneous use of pain
      coping strategies. No differences were found between the groups in pain
      tolerances, use of coping strategies, or estimates of pain intensity at
      tolerance; however, athletes who had experienced childbirth reported tolerating
      greater pain during their normal training sessions.

PMID- 10883796
TI  - Effect of delay of reinforcement on superstitious inferences.
AB  - Temporal contiguity is positively associated with ease of detecting
      contingencies. When actions and outcomes are not contiguous, intervening
      responses might be strengthened by adventitious reinforcement. In the current
      study, participants engaged in a task where pressing 1 of 10 keys was reinforced
      either immediately or after various delays. Outcomes were scheduled either
      according to an FR 1 or FR 2 schedule. Participants also answered a question
      designed to assess their illusion of control. As the latency between the
      instrumental response and the reinforcer increased, participants attributed less
      importance to the instrumental response, attributed more importance to other
      nonessential responses, and began to show stereotyped patterns of responding. The
      illusion of control was positively related to the intricacy of such patterns.
      Results are discussed in terms of a contiguity which implies causality heuristic
      and the relationship of superstition with adventitious reinforcement and illusion
      of control.

PMID- 10883797
TI  - Recognition memory and familiarity judgments in severe amnesia: no evidence for a
      contribution of repetition priming.
AB  - The amnesic patient E.P. has demonstrated normal levels of repetition priming and
      at-chance recognition performance (S. B. Hamann & L. R. Squire, 1997), suggesting
      that the sense of familiarity used to make a recognition memory judgment is not
      based on the same mechanism responsible for repetition priming. However, the
      recognition tests previously used may have discouraged the use of familiarity and
      encouraged reliance on episodic memory. This issue was addressed in 5 experiments
      with E.P., 3 other amnesic patients with hippocampal damage, and 8 healthy
      controls. In Experiments 1-3, which were designed to discourage the use of
      episodic memory, the amnesic patients were impaired and E.P. performed at chance.
      In Experiments 4 and 5A, a stem-completion priming task was combined with a
      recognition memory task on each trial. E.P.'s priming was intact, yet his
      recognition memory performance was at chance. This suggests that although
      recognition memory judgments may be made on the basis of familiarity, repetition
      priming is not the source of this feeling of familiarity.

PMID- 10883798
TI  - Dissociation of Pavlovian and instrumental incentive learning under dopamine
      antagonists.
AB  - The administration of the dopamine antagonists, pimozide and alpha-flupenthixol,
      to rats reduced Pavlovian-instrumental transfer when a conditioned stimulus (CS)
      that had been paired with a noncontingent food reward was tested on instrumental
      performance. The administration of the antagonists during Pavlovian conditioning
      and/or testing abolished the enhancement of instrumental performance by the CS.
      The effect of both antagonists on instrumental incentive learning was then
      examined. After training in which the rats performed 2 responses for different
      food rewards, they consumed 1 type food under the antagonists and the other type
      under vehicle during reexposure. When instrumental responding was subsequently
      tested in extinction, performance was unaffected by whether the rats had been
      reexposed to the training reward under the antagonists. These results suggest
      that Pavlovian and instrumental incentive learning are not mediated by a common
      process.

PMID- 10883799
TI  - Rapid and robust olfactory conditioning with milk before suckling experience:
      promotion of nipple attachment in the newborn rat.
AB  - An olfactory conditioning paradigm tested the hypothesis that newborn rats are
      able to learn about events associated with their first experience with milk as
      early as 3-5 hr after birth. Exposure to lemon odor (conditioned stimulus, [CS])
      paired with intraoral milk infusions (unconditioned stimulus, [US]) resulted in
      strong conditioning: In the presence of the CS, sustained attachment occurred to
      an empty nipple as if it provided milk, whereas pups in control conditions showed
      little attachment. A single CS-US pairing was sufficient for strong conditioning,
      which was evident with a trace interval as long as 60 s. Conditioning was robust
      enough to promote attachment to a nipple providing saline, which is aversive to
      the newborn rat, and comparably strong conditioning occurred with sucrose or
      saccharin as the US. These findings suggest that olfactory conditioning has the
      potential to modify suckling behavior.

PMID- 10883800
TI  - Context conditioning in habituation in the nematode Caenorhabditis elegans.
AB  - Habituation has traditionally been considered a nonassociative form of learning.
      However, recent research suggests that retention of this nonassociative form of
      learning may be aided by associations formed during training. An example of this
      is context conditioning, in which animals that are trained and tested in the
      presence of a contextual cue show greater retention than animals trained and
      tested in different environments. This article reports context conditioning in
      habituation in the nematode Caenorhabditis elegans. The results showed that
      retention of habituation to tap at both 10- and 60-s interstimulus intervals was
      significantly greater if training and testing occurred in the presence of the
      same chemosensory cue (NaCH3COO). This context conditioning showed both
      extinction and latent inhibition, demonstrating that these simple worms with only
      302 neurons are capable of associative context conditioning.

PMID- 10883801
TI  - Cognitive function in aged ovariectomized female rhesus monkeys.
AB  - To determine whether ovariectomy exacerbates age-related cognitive decline, the
      performance of 6 aged monkeys that had been ovariectomized early in life (OVX
      Aged) was compared to that of 8 age-matched controls with intact ovaries (INT
      Aged) and that of 5 young controls with intact ovaries (INT-Young) in tasks of
      visual recognition memory, object and spatial memory, and executive function. The
      OVX-Aged monkeys were marginally more impaired than the INT-Aged monkeys on the
      delayed nonmatching-to-sample with a 600-s delay. In contrast, they performed
      significantly better than the INT-Aged controls on the spatial condition of the
      delayed recognition span test. The hypothesis that prolonged estrogenic
      deprivation may exaggerate the age-related decline in visual recognition memory
      will require additional support. However, the findings suggest that long-term
      ovariectomy may protect against the development with aging of spatial memory
      deficits.

PMID- 10883802
TI  - Impairment of olfactory discrimination by blockade of GABA and nitric oxide
      activity in the honey bee antennal lobes.
AB  - Honey bees readily associate an odor with sucrose reinforcement, and the response
      generalizes to other odors as a function of structural similarity to the
      conditioned odor. Recent studies have shown that a portion of odor memory is
      consolidated in the antennal lobes (AL), where first-order synaptic processing of
      sensory information takes place. The AL and/or the sensory afferents that project
      into them show staining patterns for the enzyme nitric oxide synthase, which
      catalyzes the release of the gaseous transmitter nitric oxide (NO). The results
      show that pharmacological blockade of NO release impairs olfactory discrimination
      only when release is blocked before conditioning. Blockade of GABAergic
      transmission disrupts discrimination of similar but not dissimilar odorants, and
      does so when the block occurs before condition or before testing. These results
      show that GABA and NO regulate the specificity of associative olfactory memory in
      the AL.

PMID- 10883803
TI  - Sexually stimulating signals of canary (Serinus canaria) songs: evidence for a
      female-specific auditory representation in the HVc nucleus during the breeding
      season.
AB  - During the breeding season under long-day conditions, male canaries sing sexually
      attractive songs and females respond behaviorally to such songs. This study
      assessed whether auditory response properties of neurons in nucleus HVc of female
      and male canaries are tuned to sexually salient song features: special song
      phrases and canary song segmentation. In sexually receptive female canaries,
      neurons responded to special song phrases with a decreased spike rate and were
      sensitive to canary song segmentation. The nonreceptive females showed no clear
      response to special song phrases. In females on short days, neurons responded to
      song phrases with an increase in activity. In males on long days, they exhibited
      phasic responses after the phrase onset, whatever the song phrase and song
      segmentation. This study demonstrates both a plasticity in relation to females'
      sexual responsiveness and a sexual dimorphism in the auditory processing
      performed in the HVc.

PMID- 10883804
TI  - Relation of Fos-IR expression in the pelvic ganglion to sexual behavior in
      laboratory rats.
AB  - The pelvic ganglion (PG) provides both sympathetic and parasympathetic
      innervation to the genitalia and other pelvic structures. To determine whether
      neuronal activity; of the PG, as detected by Fos-like immunoreactivity (Fos-IR),
      is related to sexual stimulation, male and female rats were tested under a
      variety of conditions. In males, Fos-IR expression in the PG was positively
      correlated with the amount of both genital and noncontact stimulation. In
      females, only ejaculation preceded by multiple intromissions induced a
      significant increase in Fos-IR; multiple intromissions or ejaculation preceded by
      only 0-1 intromission did not affect Fos-IR. Additional experiments comparing Fos
      IR expression, in which some females were allowed to pace their sexual contact
      and others were not, revealed that ejaculation duration was the key factor in the
      induction of Fos-IR in female rats. Because the conditions under which Fos-IR
      expression occurred in females are identical to those required for sperm
      transport, we suggest that, in the female, sperm transport is regulated in part
      by autonomic outflow from the PG after copulation. These relations between sexual
      behavior and measures of PG activity are consistent with the idea that the
      sexually dimorphic organization of the peripheral nervous system plays a major
      role in mediating the gender-specific outcome of copulation: ejaculation in the
      male and sperm transport in the female.

PMID- 10883805
TI  - Stimulation of the medical preoptic area facilitates sexual behavior but does not
      reverse sexual satiation.
AB  - The aim of the present study was to establish whether electrical and/or drug
      stimulation of the medial preoptic area/anterior hypothalamus (mPOA/AH) surmounts
      the sexual behavior inhibition that results from copulation to exhaustion. Thus,
      intermittent electrical stimulation of the mPOA/AH (alone or combined with the
      systemic injection of yohimbine or apomorphine, at doses that were subthreshold
      for reversing sexual exhaustion) or intrapreoptic treatments to block GABAergic
      transmission were applied to sexually satiated rats. The results suggest that the
      mPOA/AH is not responsible for male sexual behavior inhibition or for the
      pharmacologically induced sexual behavior expression in satiated rats. Data are
      discussed in terms of the roles ascribed to the mPOA/AH, both in the control of
      sexual behavior expression and in the regulation of the postejaculatory interval.

PMID- 10883806
TI  - Shock-induced hyperalgesia: III. Role of the bed nucleus of the stria terminalis
      and amygdaloid nuclei.
AB  - Rats exposed to a few moderately intense (1 mA) shocks subsequently exhibit lower
      vocalization thresholds to shock and thermal stimuli. They also exhibit
      facilitated learning in a Pavlovian conditioning paradigm. Together, these
      results suggest that shock exposure can enhance pain (hyperalgesia). The present
      study examined the role of the amygdala and bed nucleus of the stria terminalis
      (BNST), 2 systems that have been implicated in the induction and maintenance of
      negative affective states. Experiment 1 showed that lesions of the central, but
      not the basolateral, amygdala eliminate shock-induced hyperalgesia as measured by
      a decrease in vocalization thresholds to shock. Experiment 2 revealed that
      central nucleus lesions also prevent shock-induced sensitization of the
      vocalization response to heat. Anterior, but not posterior, BNST lesions had a
      similar effect.

PMID- 10883807
TI  - Amygdaloid-thalamic interactions mediate the antinociceptive action of morphine
      microinjected into the periaqueductal gray.
AB  - The bilateral administration of the serotonin receptor antagonist methysergide
      (2.5 microg, 5 microg, and 10 microg) into either the central nucleus of the
      amygdala (ACe) or nucleus parafascicularis thalami (nPf) produced dose-dependent
      inhibition of the antinociceptive action of ventrolateral periaqueductal gray
      (vPAG)-administered morphine. Unilateral administration of these doses of
      methysergide into either the ACe or nPf had no effect on morphine-induced
      antinociception. However, the combined unilateral administration of these doses
      of methysergide into the ACe and nPf produced dose-dependent inhibition of
      morphine antinociception that was identical to that observed after its bilateral
      administration into either site. This latter finding is interpreted as evidence
      that a functional interaction between the ACe and nPf supports the
      antinociceptive action of morphine administered into the vPAG.

PMID- 10883808
TI  - A comparative analysis of huddling in infant Norway rats and Syrian golden
      hamsters: does endothermy modulate behavior?
AB  - In infant rats, huddling improves surface-to-volume ratios and provides metabolic
      savings during cold exposure. It is unclear, however, whether endothermy is also
      a necessary component of huddling. In the present experiment, huddles composed of
      infant Norway rats (2- or 8-day-olds), which produce heat endogenously, or Syrian
      golden hamsters (8-day-olds), which do not produce heat endogenously, were
      exposed to decreases in air temperature. Behavioral and physiological responses
      were monitored throughout the test. Rats, especially at 8 days of age, were
      better able to thermoregulate using huddling than hamsters, due in part to
      endogenous heat production. Furthermore, 8-day-old rats exhibited behavioral
      responses that promote heat retention, suggesting that both physiological and
      behavioral mechanisms contribute to effective thermoregulation during huddling in
      the cold.

PMID- 10883809
TI  - An intrinsic source of behavioral regulation that influences discrete responses
      to cues important for the initiation of suckling.
AB  - The present experiment investigated the relationship between motor activity and
      oral grasping of an artificial nipple in newborn rats. Pups orally grasped the
      artificial nipple, and they performed more and longer oral grasps in the latter
      portion of the nipple presentation. Motor activity was cyclical, and this
      cyclicity was evident before and during presentation of the artificial nipple.
      The onset of an oral grasp response was preceded by a period of relatively low
      motor activity, and the termination of a grasp was followed by relatively high
      motor activity. The newborn rat pup's intrinsic oscillations in motor activity
      may regulate the expression of discrete responses to cues important for the
      initiation of suckling.

PMID- 10883810
TI  - Cardiovascular mediation of clonidine-induced ultrasound production in infant
      rats.
AB  - In infant rats, administration of the alpha2 adrenoceptor agonist clonidine
      simultaneously evokes ultrasound production and bradycardia. In this study the
      authors examined in 8-day-old rats whether these 2 responses to clonidine are
      causally related. In Experiment 1 pups were pretreated with saline or prenalterol
      (0.1 or 1.0 mg/kg), a beta1 adrenoceptor agonist that increases cardiac rate,
      followed by administration of clonidine (1.0 mg/kg). Prenalterol pretreatment
      suppressed clonidine-induced ultrasound production at both doses. Prenalterol
      also increased skin temperature, however, suggesting that suppression of
      ultrasound was modulated in part by increased body temperature. Consistent with
      this suggestion, in Experiment 2 mild hyperthermia significantly inhibited
      clonidine-induced ultrasound production. Finally, in Experiment 3 the authors
      found that the pretreatments used in Experiments 1 and 2 prevent or dampen the
      effects of clonidine on cardiac rate. These results suggest that clonidine's
      effect on ultrasound production is mediated by its effects on the cardiovascular
      system.

PMID- 10883811
TI  - The temporal course of expression of c-Fos and Fos B within the medial preoptic
      area and other brain regions of postpartum female rats during prolonged mother-
      young interactions.
AB  - Maternal behavior is associated with an increase in the expression of c-Fos and
      Fos B within neurons of the medial preoptic area (MPOA) and ventral bed nucleus
      of the stria terminalis (vBST). Whether this increase wanes as the duration of
      mother-young interaction increases is unknown. By varying the length of mother
      young interactions in postpartum rats, the authors found that within the
      MPOA/vBST, the levels of both c-Fos and Fos B, once elevated, remained
      significantly above control levels through 47 hr of pup exposure. The persistence
      of c-Fos and Fos B within the MPOA/vBST of females that remained with pups was
      almost unique in that only one other neural area, the anterior magnocellular part
      of the paraventricular hypothalamic nucleus, showed such a response. Because
      MPOA/vBST neurons are essential for maternal behavior, the results suggest that c
      Fos and Fos B expression within these regions may be necessary to maintain their
      normal functional activity.

PMID- 10883812
TI  - Amiloride increases sodium chloride taste detection threshold in rats.
AB  - The epithelial sodium-channel blocker amiloride has been shown to inhibit sodium
      responses in the 7th cranial nerve of the rat. In the signal detection task used
      in this study, amiloride (100 microM) treatment raised the NaCl threshold by
      approximately 1 log10 unit. The inhibition constant for amiloride was 1 microM at
      0.013 M NaCl. Because the NaCl intake of adult rats has been shown to be related
      to the level of dietary NaCl exposure early in development, rats were exposed by
      way of maternal diet to 1 of 3 diets (0.1% NaCl, n = 8; 1.0% NaCl, n = 8; 3.0%
      NaCl, n = 9) from conception through weaning, to determine whether this treatment
      affects taste sensitivity. At Postnatal Day 30, rats were placed on 1.0% NaCl
      chow. This treatment did not affect NaCl detection or amiloride sensitivity in
      adulthood. The amiloride-induced shifts in NaCl sensitivity functions imply that
      the transcellular sodium transduction pathway is necessary for normal NaCl
      detection in the rat.

PMID- 10883813
TI  - Segmental control of midbody peristalsis during the consummatory phase of feeding
      in the medicinal leech, Hirudo medicinalis.
AB  - The ingestive behavior of the medicinal leech includes peristalsis-like movements
      of the midbody that are organized into both rostral-to-caudal and caudal-to
      rostral waves (C. M. Lent, K. H. Fliegner, E. Freedman, & M. H. Dickenson, 1988).
      The neuronal control of this behavior is unknown. Using surgical manipulations
      and electromyograms, the authors show that (a) the head and tail ganglia are not
      necessary for this behavior; (b) the circuit is distributed, with components
      reiterated along the length of the leech; (c) excitatory signals transmitted from
      rostral segments via the nerve cord can initiate peristalsis in "empty" caudal
      segments; (d) inhibitory signals from caudal segments limit the frequency of
      peristalsis; and (e) stretch of the gut and/or body wall is sufficient to produce
      peristalsis in the absence of heat or chemical cues. These results are compared
      with peristalsis in the digestive tract of mammals. The leech may be a good model
      for studying peristalsis-like behaviors at the cellular level.

PMID- 10883814
TI  - The effects of intra-amygdaloid infusions of a D2 dopamine receptor antagonist on
      Pavlovian fear conditioning.
AB  - The present study examined the effects of bilateral intra-amygdaloid infusions of
      the D2 receptor antagonist, eticlopride, on the acquisition and expression of
      Pavlovian fear conditioning as measured by freezing to acoustic and background
      contextual stimuli in the rat. Infusions of eticlopride before acquisition or
      before both acquisition and retention testing significantly attenuated
      conditioned freezing to tone presentations during the retention test 24 hr later.
      No effects, however, were observed on freezing that emerged during acquisition.
      Furthermore, these effects were not attributable to state-dependent learning
      effects or alterations in baseline activity or shock reactivity. In conclusion,
      these results suggest that amygdaloid dopamine transmission at D2 receptors
      contributes to the formation and/or consolidation of fear memories.

PMID- 10883815
TI  - Determination of the proton affinities of bromo- and iodoacetonitrile using the
      kinetic method with full entropy analysis
AB  - The proton affinities bromo- and iodoacetonitrile are determined using a full
      implementation of the kinetic method, which includes calculation of the
      entropies. Branching ratios for dissociation of proton-bound dimers are measured
      for collision energies ranging from approximately 2 to 5 eV. Using a rigorously
      correct statistical approach, the proton affinities of bromo- and
      iodoacetonitrile are calculated to be 179.8 +/- 1.7 and 182.9 +/- 1.6 kcal/mol,
      respectively. It is shown that neglecting the entropy contributions for these
      systems leads to proton affinities that are too high by approximately 0.6
      kcal/mol.

PMID- 10883816
TI  - Noncovalent associations of glutathione S-transferase and ligands: a study using
      electrospray quadrupole/time-of-flight mass spectrometry.
AB  - Human glutathione S-transferase A1-1 was observed predominantly as dimeric ions
      (51 kDa) during electrospray mass spectrometric analysis from aqueous solution at
      pH 7.4, in keeping with the known dimeric structure in solution. When analyses
      were performed on solutions of the enzyme containing glutathione (GSH),
      noncovalent adducts of protein dimer and one or two ligand molecules were
      observed; each mass increment, which exceeded the mass of GSH alone, was
      provisionally interpreted to indicate concomitant association of two water
      molecules per bound GSH. Noncovalent adducts of ligand and protein dimer were
      similarly observed for oxidized glutathione and for two glutathione inhibitors,
      both incorporating substituted thiol structures. In these instances, the mass
      increments exactly matched the ligand masses, suggesting that the apparent
      concomitant binding of water was associated with the presence in the ligand of a
      free thiol group. Collisionally activated decomposition during tandem mass
      spectrometry analyses of noncovalent adducts incorporating protein dimer and
      ligands yielded initially the denuded dimer; at higher collision energies the
      monomer and a protein fragment were formed.

PMID- 10883818
TI  - Fragmentation chemistry of [M + Cu]+ peptide ions containing an N-terminal
      arginine.
AB  - [M + Cu]+ peptide ions formed by matrix-assisted laser desorption/ionization from
      direct desorption off a copper sample stage have sufficient internal energy to
      undergo metastable ion dissociation in a time-of-flight mass spectrometer. On the
      basis of fragmentation chemistry of peptides containing an N-terminal arginine,
      we propose the primary Cu+ ion binding site is the N-terminal arginine with Cu+
      binding to the guanidine group of arginine and the N-terminal amine. The
      principal decay products of [M + Cu]+ peptide ions containing an N-terminal
      arginine are [a(n) + Cu - H]+ and [b(n) + Cu - H]+ fragments. We show evidence to
      suggest that [a(n) + Cu - H]+ fragment ions are formed by elimination of CO from
      [b(n) + Cu - H]+ ions and by direct backbone cleavage. We conclude that Cu+
      ionizes the peptide by attaching to the N-terminal arginine residue; however,
      fragmentation occurs remote from the Cu+ ion attachment site involving metal ion
      promoted deprotonation to generate a new site of protonation. That is, the
      fragmentation reactions of [M + Cu]+ ions can be described in terms of a "mobile
      proton" model. Furthermore, proline residues that are adjacent to the N-terminal
      arginine do not inhibit formation of [b(n) + Cu - H]+ ion, whereas proline
      residues that are distant to the charge carrying arginine inhibit formation of
      [b(n) + Cu - H]+ ions. An unusual fragment ion, [c(n) + Cu + H]+, is also
      observed for peptides containing lysine, glutamine, or asparagine in close
      proximity to the Cu+ carrying N-terminal arginine. Mechanisms for formation of
      this fragment ion are also proposed.

PMID- 10883817
TI  - An experimental and theoretical study of the gas-phase decomposition of
      monoprotonated peptide nucleic acids.
AB  - Peptide nucleic acids (PNAs) are DNA/RNA mimics which have recently generated
      considerable interest due to their potential use as antisense and antigene
      therapeutics and as diagnostic and molecular biology tools. These synthetic
      biomolecules were designed with improved properties over corresponding
      oligonucleotides such as greater binding affinity to complementary nucleic acids,
      enhanced cellular uptake, and greater stability in biological systems. Because of
      the stability and unique structure of PNAs, traditional sequence confirmation
      methods are not effective. Alternatively, electrospray ionization coupled with
      Fourier transform ion cyclotron resonance mass spectrometry shows great potential
      as a tool for the characterization and structural elucidation of these
      oligonucleotide analogs. Extensive gas-phase fragmentation studies of a mixed
      nucleobase 4-mer (AACT) and a mixed nucleobase 4-mer with an acetylated N
      terminus (N-acetylated AACT) have been performed. Gas-phase collision-induced
      dissociation of PNAs resulted in water loss, cleavage of the methylene carbonyl
      linker containing a nucleobase, cleavage of the peptide bond, and the loss of
      nucleobases. These studies show that the fragmentation behavior of PNAs resembles
      that of both peptides and oligonucleotides. Molecular mechanics (MM+),
      semiempirical (AM1), and ab initio (STO-3G) calculations were used to investigate
      the site of protonation and determine potential low energy conformations.
      Computational methods were also employed to study prospective intramolecular
      interactions and provide insight into potential fragmentation mechanisms.

PMID- 10883819
TI  - Structural effects on polyether cationization by alkali metal ions in matrix
      assisted laser desorption/ionization
AB  - Structural effects on polyether cationization in matrix-assisted laser
      desorption/ionization (MALDI) are investigated using three different polyethers:
      PEG (polyethylene glycol), PPG (polypropylene glycol), and PTHF
      (polytetrahydrofuran). This study was performed using equimolar cesium and
      lithium chlorides as the cationizing agent. It was observed that the polyether
      structure variation led to a substantial change in polyether selectivity for
      alkali metal ion complexation. Moreover, it was found that like PEG, PPG displays
      a different selectivity for Cs+ and Li+ with different matrices. Discussion of
      these results and their implication in MALDI are given.

PMID- 10883820
TI  - An activated carbon substrate surface for laser desorption mass spectrometry
AB  - A method to obtain laser desorption/ionization mass spectra of organic compounds
      by depositing sample solutions onto a carbon substrate surface is demonstrated.
      The substrate consists of a thin layer of activated carbon particles immobilized
      on an aluminum support. In common with the porous carbon suspension samples used
      in previous "surface-assisted laser desorption/ionization" (SALDI) work, the mass
      spectra contain only a few "matrix" background ion peaks, minimizing interference
      with analyte ion peaks. The presence of glycerol ensured that the ion signals
      were stable over hundreds of laser shots. In addition, the carbon substrate
      surface has several advantages over the suspension samples. The use of a very
      thin layer of carbon significantly improves the sensitivity. Detection limits
      range from attomoles for crystal violet to femtomoles for bradykinin. Very little
      sample preparation is required as the analyte solution is simply pipetted onto
      the substrate surface and glycerol added. When using an alternate sample
      deposition method, a mass resolution for bradykinin of 1800 is achieved in linear
      time-of-flight mode. This is close to the resolution limit set by the detector
      system and above instrument specification for matrix-assisted laser
      desorption/ionization mass spectra.

PMID- 10883821
TI  - Investigation of the formation process of MCs+-molecular ions during sputtering
AB  - In secondary ion mass spectrometry, the detection of MCs+ clusters (with M an
      element of the specimen) under a Cs bombardment is frequently used for the
      quantification of major elements. Despite some very good results obtained by this
      method, some problems still remain. In order to gain some more insight into these
      problems, the formation mechanism of the MCs+ clusters is investigated using a
      Monte Carlo model. It is shown that the majority of the constituent particles of
      the formed clusters are initially first or second neighbor atoms at the surface
      and that the velocity distribution of the MCs+ clusters becomes broader and
      peaked at higher velocities with increasing surface binding energy of the M atom.
      In addition, it is demonstrated that the interaction potential between the M and
      Cs+ particle has no influence on the velocity distribution of the MCs+ clusters.
      On the other hand, the cluster formation probability, defined as the probability
      that a sputtered M and Cs+ particle will form a MCs+ cluster, is extremely
      sensitive to this interaction potential. It is also shown that the cluster
      formation probability decreases with increasing surface binding energy. Finally,
      a good correspondence is obtained between the calculated and experimental
      velocity distributions of MCs+ clusters sputtered from different monoatomic
      materials. As a consequence, the Monte Carlo model and the discussed results can
      be validated.

PMID- 10883822
TI  - Polyaniline: a conductive polymer coating for durable nanospray emitters
AB  - Despite the tremendous sensitivity and lower sample requirements for nanospray
      vs. conventional electrospray, metallized nanospray emitters have suffered from
      one of two problems: low mechanical stability (leading to emitter failure) or
      lengthy, tedious production methods. Here, we describe a simple alternative to
      metallized tips using polyaniline (PANI), a synthetic polymer well known for its
      high conductivity, anticorrosion properties, antistatic properties, and
      mechanical stability. A simple method for coating borosilicate emitters (1.2 mm
      o.d.) pulled to fine tapers (4 +/- 1 microm) with water-soluble and xylene
      soluble dispersions of conductive polyaniline (which allows for electrical
      contact at the emitter outlet) is described. The polyaniline-coated emitters show
      high durability and are resistant to electrical discharge, likely because of the
      thick (yet optically transparent) coatings; a single emitter can be used over a
      period of days for multiple samples with no visible indication of the destruction
      of the polyaniline coating. The optical transparency of the coating also allows
      the user to visualize the sample plug loaded into the emitter. Examples of
      nanospray using coatings of the water-soluble and xylene-soluble polyaniline
      dispersions are given. A comparison of PANI-coated and gold-coated nanospray
      emitters to conventional electrospray ionization (ESI) show that PANI-coated
      emitters provide similar enhanced sensitivity that gold-coated emitters exhibit
      vs. conventional ESI.

PMID- 10883823
TI  - Use of preoperative erythropoietin in head and neck surgery.
AB  - OBJECTIVE: To determine whether preoperative erythropoietin can raise the
      hemoglobin levels of head and neck cancer patients prior to major ablative
      surgery. STUDY DESIGN: Prospective, consecutive series. METHODS: Ten patients who
      were to undergo major head and neck surgery were scheduled to receive
      subcutaneous doses of erythropoietin (600 IU/kg) on days 21, 14, 7, and 1 prior
      to surgery. Serial hemoglobin levels and reticulocyte counts were obtained
      throughout the course of treatment. RESULTS: Eight patients experienced a
      significant increase in hemoglobin. There were two nonresponders. The mean
      preoperative hemoglobin level for all 10 patients increased 12.6 g/L, from 135.5
      +/- 16.2 g/L (baseline) to 148.1 +/- 23.7 g/L (1 day preoperatively, p < .0001).
      CONCLUSIONS: Erythropoietin significantly increases hemoglobin levels in patients
      awaiting major head and neck oncologic surgery. It can be viewed as an important
      adjunct to other well-established blood conservation techniques aimed at reducing
      perioperative transfusion rates.

PMID- 10883824
TI  - U-shaped free jejunal transplantation: improved technique and indications.
AB  - Reconstruction of the oropharynx and the hypopharynx is difficult due to their
      wide diameters. We report eight cases of circumferential pharyngolaryngectomies
      for epidermoid carcinomas of the hypopharynx extended to the oropharynx and
      classified T4. Reconstruction was performed with a U-shaped free jejunal
      transplantation. This specific technique consists of a side to side anastomosis
      between two loops of jejunum. It facilitates reconstruction at the level of the
      oropharynx and diminishes postoperative complications.

PMID- 10883825
TI  - Minimally invasive KTP laser treatment of perennial allergic rhinitis: a
      preliminary report.
AB  - OBJECTIVE: To test the efficacy of KTP laser in controlling perennial allergic
      rhinitis symptoms in a minimally invasive fashion. MATERIALS AND METHODS: Fifty
      eight cases of refractory perennial allergic rhinitis were included in this self
      controlled study. The anterior one-fourth of the inferior turbinate of one side
      of the nose was lased by KTP laser at 12 watts, continuous mode, the total energy
      per side ranging from 121 to 440 joules (mean = 252). The other side of the nose
      was left untreated to serve as a control. The longest follow-up time was 20
      months. RESULTS: Five patients were lost to follow-up; 53 patients were available
      for evaluation. For the overall result, 81% of patients reported good to
      excellent subjective improvement, 16.6% had fair, and 1.8% had poor subjective
      improvement of symptoms. The mean (+/- SD) degree of improvement in the treated
      and untreated sides was 77.1 +/- 17.8% and 38.4 +/- 29.4%, respectively; this was
      statistically significant (p < .001). This improvement remained at 20 months
      follow-up, and there were no complications. CONCLUSION: A single minimally
      invasive KTP laser treatment of perennial allergic rhinitis according to the
      parameters employed in this study is an effective approach resulting in
      moderately long-term improvement.

PMID- 10883826
TI  - Middle turbinate medialization technique in functional endoscopic sinus surgery.
AB  - The middle turbinate is an important surgical landmark in functional endoscopic
      sinus surgery (FESS). Postoperatively, lateralization may obstruct the middle
      meatus, thereby increasing the risk of complications and recurrences. A new
      medialization technique using metallic clips between the head of the middle
      turbinate and the septum is described. The aim of this study is to evaluate the
      clip medialization technique applied in 56 cases of bilateral FESS. We think that
      this simple technique, with its low rate of complications, is an adequate and
      simple procedure for middle turbinate medialization. A good and accessible middle
      meatus was observed in 54 patients.

PMID- 10883827
TI  - Clinicomicrobiologic evaluation of active tubotympanic type chronic suppurative
      otitis media.
AB  - OBJECTIVES: This prospective study was conducted to determine the spectrum of
      micro-organisms encountered in patients with active-stage chronic suppurative
      otitis media (CSOM) (tubotympanic type) and to see whether prescribing an
      antibiotic after culture sensitivity was more beneficial as compared to initial
      treatment without cultures. DESIGN: Prospective randomized study of 110 patients
      of active CSOM (tubotympanic type) divided into two groups of 55 cases each.
      SETTING: Departments of Ear, Nose and Throat and Microbiology of a tertiary care
      hospital. METHODS: The patients in group A were prescribed an antibiotic
      according to the culture and sensitivity, whereas in group B, culture was not
      done at the first visit, and a broad-spectrum antimicrobial, namely, co
      trimoxazole, was prescribed blindly for a maximum period of 2 weeks. The cases
      that still had ear discharge were then subjected to culture and sensitivity and
      the antibiotic was prescribed accordingly. MAIN OUTCOME MEASURES: All patients in
      group A were subjected to bacterial culture and sensitivity and fungal culture.
      Only failed cases in group B were subjected to the same. RESULTS: In group A, 47
      patients (85.50%) had positive bacterial culture and 20 patients had positive
      fungal culture. Pseudomonas aeruginosa was the most common bacterial isolate. All
      of these 47 patients had a dry ear with a maximum 2 weeks of antibiotic therapy.
      Among the remaining 8 patients who had negative bacterial culture, 5 patients
      (9.0%) showed fungal isolates on culture and responded to topical antifungal
      treatment. The remaining 3 failed cases (5.5%) responded to daily dry mopping
      alone. In group B, 41 patients (74.54%) attained a dry ear. Bacterial culture and
      sensitivity were done in the remaining 14 (25.46%) failed cases. The culture was
      positive in 11 patients (20.0%) and sterile in 3 patients (5.5%). In the latter
      group, only 1 patient had fungus on culture and the remaining 2 patients
      responded to daily dry mopping alone, which was done at a maximum for a week
      only. The most common fungal pathogen isolated was Aspergillus flavus.
      CONCLUSIONS: Pseudomonas aeruginosa was the most common bacteria and Aspergillus
      flavus the most common fungus isolated in this study. In group A patients, the
      failed cases were less as compared to the control group B, but the p value was
      .2. Hence, there is no definite role of culture and sensitivity in the initial
      management plan of all cases of CSOM. Ideally, every such case should be
      prescribed a broad-spectrum antibiotic and only in failed cases should culture
      and sensitivity be done.

PMID- 10883828
TI  - Psychological findings in benign paroxysmal positional vertigo and psychogenic
      vertigo.
AB  - OBJECTIVE: A prospective study conducted at the Post Graduate Institute of
      Medical Education and Research, Chandigarh, India, to study the psychological
      factors in cases of benign paroxysmal positional vertigo (BPPV) and to compare
      them with patients with psychogenic vertigo. METHODS: In the present study, 75
      subjects each (25-45 years) with BPPV and psychogenic vertigo were compared with
      an equal number of age- and sex-matched normal controls using the psychological
      and audiovestibular test batteries. RESULTS: The psychological variables tested,
      namely, loneliness, depression, anxiety components, introversion, and social
      desirability, were found to be statistically significant (p < .01) for the three
      groups (i.e., BPPV, psychogenic, and control). There was no significant
      difference among the three groups on the audiovestibular measures. CONCLUSION:
      Psychological factors play an important role in patients with BPPV. The provoking
      activities result in precipitation of an acute attack and the patients experience
      heightened emotionality because of the incapacitating feeling of severe vertigo.

PMID- 10883829
TI  - Connections of the facial and vestibular nerves: an anatomic study.
AB  - The facial and vestibulocochlear nerves emanate from the brain stem and then run
      parallel to each other within the internal auditory canal prior to their more
      peripheral distribution. Although anatomic connections between the facial and
      cochlear nerves have been described, reports outlining facial-vestibular
      anastomoses are few and may be found primarily in the non-English literature. The
      present study documents the existence of vestibulofacial neural connections as
      part of an anatomic dissection of 17 fresh human temporal bones.

PMID- 10883830
TI  - Impact of vertical dome division on nasal airflow.
AB  - OBJECTIVE: Vertical dome division is an effective maneuver in nasal tip surgery.
      Its applications include reduction of the tip projection, increasing tip
      rotation, narrowing of the domal arch, and correction of lobule asymmetry.
      Nevertheless, some surgeons avoid this technique, fearing tip deformity and
      possibly impaired nasal airflow. RESULTS: In this study, nasal airflow
      measurements were made before and after septorhinoplasty with vertical dome
      division. There was no significant change in the airflow before and after
      septorhinoplasty with vertical dome division. The airflow was negatively affected
      in 37.5% and improved postoperatively in 25% of patients. CONCLUSIONS: Despite
      objective findings of diminished nasal airflow in some patients following
      vertical dome division, no subjective correlation was identified. Furthermore,
      during the postoperative testing, alar retraction on all of these patients failed
      to normalize airflow results, indicating that alar collapse was not contributing
      to the airflow impairment in those cases. All of the patients were found
      clinically asymptomatic after surgery.

PMID- 10883831
TI  - [Intramasseter hemangiomas: a case report].
AB  - Intramuscular hemangiomas are uncommon tumours in the head and neck region,
      especially in the masseter muscle. This article presents a case of a 10-year-old
      male treated by surgical excision. The authors review the literature to discuss
      the clinical characteristics, sex, age, differential diagnosis, surgical
      approaches, and histology.

PMID- 10883832
TI  - Is there a correlation between radiographic and histologic findings in chronic
      sinusitis?
AB  - OBJECTIVE: To determine if the degree of radiologic changes noted on computed
      tomography (CT) scan correlate with the severity of histologic changes. DESIGN:
      Retrospective analysis. SETTING: Academic tertiary care centre. METHODS: Sixty
      consecutive patients undergoing endoscopic sinus surgery for chronic sinusitis,
      with complete data obtained for 131 sinuses. MAIN OUTCOME MEASURES: Paranasal
      sinus CT scans and pathologic reports were examined. Respective findings were
      graded as mild, moderate, or severe, and the results were analyzed for agreement.
      CT scan grading was based on the extent of sinus opacification and pathologic
      grading was determined by the number of inflammatory cells found in the sinus
      mucosa. RESULTS: Of the 51 ethmoid sinuses, agreement between the radiographic
      and histologic grading occurred in 32 or 62.7%. In the maxillary group, a 57.1%
      (24 of 42) correlation was noted. Of the 20 frontal sinuses, agreement occurred
      in 8 or 40%, whereas a 22.2% (4 of 18) correlation was present in the sphenoid
      group. CONCLUSION: This study suggests that the severity of sinus disease based
      on preoperative CT scan does not correlate with the histologic degree of disease.

PMID- 10883833
TI  - Two cases of thyroid carcinoma producing granulocyte colony-stimulating factor.

PMID- 10883834
TI  - Laryngeal manifestations in Opitz BBB/G syndrome.

PMID- 10883835
TI  - Lymphomas presenting in Waldeyer's ring.

PMID- 10883836
TI  - Third branchial cleft anomaly detected in utero.

PMID- 10883837
TI  - Congenital cervical teratoma with pressure deformity of the trachea.

PMID- 10883838
TI  - Cavernous lymphangioma of adult parotid gland in a non-Caucasian female.

PMID- 10883839
TI  - Survival and viability of vitrified in vitro and in vivo produced ovine
      blastocysts.
AB  - Ovine blastocysts were produced by maturation, fertilization and in vitro culture
      (IVM/IVF/IVC) of oocytes from slaughtered adult and prepubertal ewes and
      collection from superovulated and inseminated adult animals. Dulbecco's PBS
      supplemented with 0.3 mM Na Pyruvate and 20% FCS was used as the basic
      cryopreservation solution. The embryos were exposed to the vitrification solution
      as follows: 10% glycerol (G) for 5 min, then 10% G +20% ethylene glycol (EG) for
      5 min. Embryos were placed into 25% G + 25% EG in the center of 0.25- mL straws
      and plunged immediately into LN2. Warming was done by placing the straws into a
      water bath at 37 degrees C for 20 sec, and their contents were expelled into a
      0.5 M sucrose solution for 3 min; the embryos were then transferred into 0.25 M
      and 0.125 M sucrose solution for 3 min each. Warmed blastocysts were transferred
      to the culture medium for 24 h. Survival was defined as the re-expansion of the
      blastocoele. All surviving blastocysts were transferred to synchronized recipient
      ewes, and the pregnancy was allowed to go to term. Of 68 vitrified in vitro
      produced blastocysts, 46 re-expanded (67.6%) and 10 lambs were born (14.7%). From
      the 62 in vivo derived and vitrified embryos, 52 re-expanded (83.8%) and 39 lambs
      were born (62.9%). The lambing rate of in vitro produced fresh transfer embryos
      was 40% (20 lambs/50 blastocysts transferred), and of the 32 in vivo derived
      blastocysts and transferred fresh, 26 lambs were born (81.2%). The results
      indicate that in vitro produced embryos can be successfully cryopreserved by
      vitrification.

PMID- 10883840
TI  - Recovery rates and embryo quality following dominant follicle ablation in
      superovulated cattle.
AB  - To determine the association between dominant follicle ablation and the outcome
      of a superovulatory regimen, two data sets were constructed from records of 171
      recoveries from non-ablated cows and 1214 recoveries from cows that underwent
      follicular ablation prior to FSH treatment. Data set 1 included all cows with 2
      or more records (n = 1385). Data set 2 included paired data for 87 cows which had
      at least 2 records of both ablated and non-ablated superovulatory attempts.
      Dominant follicle ablation was performed by use of transvaginal, ultrasound
      guided aspiration 48 hr prior to the start of FSH. The same FSH protocols were
      used for both ablated and non-ablated cows. For all cows (data set 1), more total
      ova/embryos were recovered from the ablation group (12.1+/-0.3 vs 10.5+/-0.8;
      P=0.06). This difference could be accounted for by greater numbers of non
      transferable embryos in the ablation group (6.5+/-0.2 vs 5.3+/-0.6; P>0.01). For
      the paired data (data set 2), greater numbers of total ova/embryos recovered from
      the ablation group (12.8+/-1.0 vs 9.7+/-0.7; P=0.01) could also be accounted for
      by higher numbers of nontransferable embryos in this group (7.8+/-0.8 vs 4.5+/
      0.4; P>0.01). There were no differences between groups for high quality embryos,
      percent cows producing no ova/embryos or percent cows producing no transferable
      embryos. These data support the premise that synchronization of follicular waves
      following dominant follicle ablation increases total ova/embryo output. However,
      the additional embryos were primarily nontransferable thereby negating potential
      economic gains.

PMID- 10883841
TI  - Embryo development in vitro of cat oocytes cryopreserved at different maturation
      stages.
AB  - The purpose of this study was to evaluate the ability of cat oocytes, at
      different stages of maturation, to survive after cryopreservation and to assess
      their subsequent development following IVM and IVF. In the initial toxicity
      trial, immature oocytes were exposed to different concentrations of DMSO and
      ethylene glycol (EG). Resumption of meiosis and metaphase II were evaluated after
      removal of the cryoprotectant and IVM. The highest rates of resumption of meiosis
      (51.4%) were achieved after exposure to 1.5 mol l(-1) of cryoprotectants, and no
      difference was observed with control oocytes. Metaphase II was obtained in 25.7%
      (P<0.01) and 22.9% (P<0.005) of oocytes exposed to 1.5 mol l(-1) of DMSO and
      ethylene glycol, although at lower rates than in control oocytes (54.4%). On the
      basis of this finding, 1.5 mol l(-1) of cryoprotectant was chosen for freezing
      cat oocytes at the germinal vesicle stage (immature) or at metaphase II stage
      (mature). Post-thaw viability was assessed by the evaluation of the embryo
      development in vitro. After fertilization, mature oocytes frozen in ethylene
      glycol cleaved in better proportions (38.7%) than immature oocytes (6.8%,
      P<0.001), and no differences were observed in the cleavage rate of oocytes frozen
      at different maturation stages with DMSO (immature 12.8%; mature 14.1%).
      Embryonic development beyond the 8-cell stage was obtained only when mature
      oocytes were frozen with ethylene glycol (11.3%). This study suggests that
      cryopreserved cat oocytes can be fertilized successfully and that their
      development in vitro is enhanced when mature oocytes are frozen with ethylene
      glycol. The stage of maturation may be a key element in improving cat oocyte
      cryopreservation.

PMID- 10883842
TI  - Transrectal Doppler sonography of uterine blood flow.
AB  - Transrectal Doppler ultrasound was used for the noninvasive investigation of
      uterine blood flow in cows. Both the left and right Aa. uterinae were scanned to
      obtain blood flow velocity waveforms over 2 consecutive estrous cycles. Blood
      flow was reflected by the resistance index (RI) and the time-averaged maximum
      velocity (TAMV). Intra-observer reproducibility of Doppler measurements was
      evaluated. The intra-class correlation coefficient (Intra-CC) was 0.97 for the RI
      and 0.95 for TAMV. While RI values did not differ between the left and right A.
      uterina (P > 0.05), differences in TAMV occurred between both vessels in 2 cows.
      These differences were not related to the ovary bearing the dominant follicle or
      to the corpus luteum (P < 0.001). As in all cows, changes of RI and TAMV values
      between the left and right artery during the estrous cycle were correlated
      (correlation coefficient r > 0.72; P < 0.0001); the mean values of both sides
      were used for subsequent analyses. Variance component estimates for the effect of
      cow on RI and TAMV were 8 and 13% and for the influence of day of estrous cycle
      they were 70 and 47%, respectively (P <0.0001). Between estrous cycles no
      significant differences could be measured within cows (P > 0.05). The highest RI
      and lowest TAMV values occurred on Day 0 (= day of ovulation) and Day 1, while
      the lowest RI and highest TAMV values were measured between Days -3 and -1 of the
      estrous cycle, respectively. There was a positive correlation between TAMV and
      estrogen concentrations and a negative correlation between RI and plasma estrogen
      levels. Plasma progesterone levels and TAMV were negatively correlated, but no
      correlation could be measured (P > 0.05) between RI values and plasma
      progesterone concentrations. While there were no differences in plasma
      concentrations of estrogens and progesterone between estrous cycles within cows,
      the levels of these hormones differed between cows. The results show that
      transrectal Doppler sonography is a useful, noninvasive method for examining
      uterine blood flows in cows. If there is an influence of uterine perfusion on
      fertility in cows its role needs further investigation.

PMID- 10883843
TI  - Fertilizability and developmental capacity of individually cultured bovine
      oocytes.
AB  - Culture of single oocytes throughout in vitro maturation (IVM), fertilization
      (IVF) and culture (IVC) provides detailed information on maturity,
      fertilizability and developmental capacity of individual bovine oocytes and
      embryos. In the present study, effects of sperm concentration (Experiment 1),
      microdrop size (Experiment 2), and the addition of hypotaurine (HT) or
      glutathione (GSH; Experiment 3) during IVF were investigated. In Experiment 4, in
      vitro maturity and developmental capacity of bovine oocytes cultured for IVM in a
      medium supplemented with fetal calf serum (FCS), bovine serum albumin (BSA) or
      polyvinyl alcohol (PVA) during IVM were investigated. In Experiments 1 to 3, the
      percentages of normal (2 pronuclei with a spermtail) and polyspermic
      fertilization in singly cultured oocytes were similar to those of group IVF
      culture (5 oocytes/drop). The addition of GSH during single oocyte IVF
      significantly increased the proportion of normal fertilization and decreased the
      polyspermic fertilization compared with addition of HT or of the control. The
      rates of mature oocytes (62.4 and 67.7%) and blastocyst development (12.9 and
      15.2%) for single oocyte IVM cultures (Experiment 4) were also similar compared
      with the group culture; PVA supplementation significantly increased the matured
      oocyte rate, but decreased blastocyst development significantly (7.1%) as
      compared with FCS (19.5%) or BSA (15.6%). These results indicate that a single
      oocyte culture system throughout in vitro production of bovine embryos provides
      similar maturity, fertilizability and developmental capacity to oocytes cultured
      in groups.

PMID- 10883844
TI  - A comparison of the effects of progesterone sponges and ear implants, PGF2alpha,
      and their combination on efficacy of estrus synchronization and fertility of
      Mashona goat does.
AB  - Efficacy of estrus synchronization and fertility after synchronization of 60
      multiparous Mashona goat does using intravaginal progesterone (P4) sponges (Group
      1), norgestomet ear implants (Group 2), cloprostenol (Group 3), or a combination
      of P4 sponges and cloprostenol (Group 4) was compared with untreated does (Group
      5). At the end of treatments, all does were mated to intact fertile bucks for 21
      d. The number of does bred within 11 to 96 h was significantly higher (P < 0.05)
      in the treated groups than the untreated control, with rates of 80, 80, 64, 67
      and 30% for Groups 1 to 5, respectively. There were no differences (P > 0.05)
      among treated does. Kidding rates ranged from 64 to 83% but were not different (P
      > 0.05) between groups. Prolificacy and overall fecundity were similar (P > 0.05)
      among the groups. The results indicate that all 4 treatment methods were
      effective in synchronizing estrus and that none of the methods affected overall
      fertility of the does.

PMID- 10883845
TI  - Influence of somatotropin and nutrition on bovine oocyte retrieval and in vitro
      development.
AB  - The objective of this study was to determine the effects of supplemental bovine
      somatotropin (bST) and limit feeding on follicular growth and oocyte competence
      in yearling beef heifers. Sixteen growing heifers (424+/-4 kg) were randomly
      assigned to 1 of 4 treatments in a 2 x 2 factorial arrangement, with main effects
      of bST (0 or 33 microg/kg BW/d) and feeding regimen (ad libitum or 0.75 ad
      libitum intake). Animals were treated for 100 d prior to follicular aspiration,
      and treatments continued for the 42-d period that follicles were aspirated.
      Follicles were observed ultrasonically then aspirated, and recovered oocytes were
      matured, fertilized and developed in vitro. The number of follicles observed
      ultrasonically was greater with bST treatment (P<0.01) but was unchanged by plane
      of nutrition. The number and quality of recovered oocytes were similar among
      treatments, as was the number of oocytes resulting in blastocyst formation.

PMID- 10883846
TI  - Peripheral and intrauterine neutrophil function in the cow: the influence of
      endogenous and exogenous sex steroid hormones.
AB  - It has been accepted for many years that the susceptibility of the genital tract
      to infection is reduced during the follicular phase compared with the luteal
      phase of the estrous cycle. Since the role of intrauterine neutrophils is
      paramount in the elimination of bacteria, it can be hypothesized that these
      differences in resistance to infection could be mediated by differences in
      uterine-derived neutrophil function. In order to test this hypothesis two groups
      of cows were used in this study. Group 1 cows (n=5) were studied at estrus,
      diestrus, after ovariectomy, after exogenous estradiol and after progesterone
      treatment, at which time they underwent intrauterine infusion with 1% oyster
      glycogen (OG) and a bacterial-free filtrate (BFF) of Actinomyces genes (BFF), the
      latter having been recovered from a clinical case of endometritis; neutrophils
      were harvested by flushing from the lumen 15 to 18 h later. A peripheral blood
      sample was collected at the time of flushing for the assay of estradiol and
      progesterone for a WBC and differential count and for the harvesting of
      neutrophils using a Percoll single-stage discontinuous gradient. After the
      recovery of the cells they were re-suspended in HBSS. Group 2 (n=4) were infused
      with BFF during during all reproductive states as Group 1, but with OG only after
      ovariectomy and after treatment with progesterone and estradiol. Neutrophil
      chemotaxis was assessed by measuring their migration using a modified Boyden
      chamber and Zymogen-activated serum as a chemoattractant. Phagocytic activity was
      measured by determining the number of Candida albicans ingested by each
      neutrophil after incubation. The percentage of kill was determined using a
      radiometric assay in which C. albicans was labeled with L-(5-3H) Proline.
      Peripheral WBC concentration was not influenced by the reproductive state of the
      cow; however, the mean neutrophil concentration was significantly different
      between the reproductive states (P<0.001) and between individual cows (P<0.001).
      In Group 1, there was little difference in the function of the peripheral and
      uterine neutrophils, and while there were differences in all 3 aspects of
      neutrophil function from both sources between reproductive states and individual
      cows, of which some were statistically significant, there was no consistent
      pattern. In Group 2, neutrophils recovered after the infusion of BFF had poorer
      function compared with those recovered after the infusion of OG. There was no
      consistent influence of the reproductive state or individual animal. The
      hypothesis that the influence of the reproductive state of the cow on the
      resistance of the uterus to infection is mediated by the inherent differences in
      either peripheral or intrauterine neutrophil function was not supported by this
      study.

PMID- 10883847
TI  - Oviductal isthmic motility in relation to ovulation and endocrine changes in
      unrestrained sows.
AB  - This study was designed to characterize changes in the motility of the oviductal
      isthmus in relation to endocrine changes around ovulation in unrestrained sows in
      their normal environment. Oviductal isthmic motility was monitored on Polyview
      from 11 h prior to and up to 36 h after ovulation in 13 unrestrained multiparous
      sows during their second estrus after weaning, using a pressure microtransducer
      implanted 3 cm into the isthmus. Both the maximum, minimum and mean pressures and
      the frequency of phasic pressure fluctuations were high prior to ovulation but
      declined significantly (P<0.05) at 9 to 12 h, 13 to 16 h, 13 to 16 h and 5 to 8 h
      after ovulation, respectively. Plasma estradiol-17beta and prostaglandin F2alpha
      metabolite levels declined significantly (P<0.05) at 4 to 7 h prior to ovulation
      while progesterone levels increased significantly (P<0.01) at 5 to 8 h after
      ovulation. The decrease in the plasma estradiol-17beta levels was correlated to
      the decrease in maximum and mean pressures and the frequency of phasic pressure
      fluctuations (n=113; r=0.30, 0.25, 0.25, respectively; P<0.01) but not to the
      decrease in minimum pressure (n=113; r=0.17, P>0.05). Similarly, the decrease in
      PGF2alpha metabolite levels was correlated to the decrease in minimum, maximum
      and mean pressures and the frequency of phasic pressure fluctuations (n=112;
      r=0.43, 0.35, 0.38, 0.32, respectively; P<0.001). Conversely, the increase in
      plasma progesterone levels was correlated to the decrease in minimum, maximum and
      mean pressures and the frequency of phasic pressure fluctuations (n=113; r=-0.56,
      -0.70, -0.68, -0.60, respectively; P<0.001). Therefore, the pressure parameters
      seem to be influenced by changes in the levels of estradiol-17beta, prostaglandin
      F2alpha and progesterone with respect to ovulation.

PMID- 10883848
TI  - Developmental potential of cumulus cell-derived culture frozen in a quiescent
      state after nucleus transfer.
AB  - An efficient method for freezing donor cells is necessary when using nucleus
      transfer of somatic cells for large-scale cloning. In the present study, we
      developed a method for freezing and thawing bovine cumulus cell-derived cultured
      cells to be used as nucleus donors. Cumulus cells were obtained from ovaries of
      living and slaughtered bovine and cultured in vitro. Cumulus cell-derived
      cultured cells were serum-starved for several days to induce a quiescent state
      and then frozen at -70 degrees C for at least 2 d. Immediately thereafter or 2 h
      after thawing, the cells were used as donor cells for nuclear transfer without
      additional in vitro culture. The fusion rate with recipient cytoplasts was not
      affected by the cumulus cell source (slaughtered or living) or time after thawing
      (0 and 2 h). The cleavage rate of frozen-thawed cumulus cell-derived cultured
      cells from slaughtered cows immediately after thawing (0 h) was highest (97%) and
      was significantly higher than that of controls (85%) or cells transferred 2 h
      after thawing (85%). There were no significant differences among any of the
      groups in the potential of the nuclear transfer embryos to develop into
      blastocysts (34 vs 44 and 44%, 39 vs 45 and 46%). Thus, storage of bovine cumulus
      cell-derived cultured cells in the quiescent state at -70 degrees C is effective
      and might be useful and convenient for large-scale cloning. The maximum storage
      periods and developmental potential of embryos after such nucleus transfers
      requires further examination.

PMID- 10883849
TI  - Ovarian consequences of low dose peroral Fusarium (T-2) toxin in a ewe and heifer
      model.
AB  - The effect of low dose peroral Fusarium produced T-2 toxin intake upon the
      ovarian function was evaluated in ewes (n = 30; Trial 1) and heifers (n = 7;
      Trial 2). Half of the ewes and all of the heifers were fed rich, acidosis
      inducing concentrate. The 30 ewes were divided into 6 groups of 5 animals each.
      They were given 0, 0.3 or 0.9 mg/day (0, 5 or 15 ug/kg) purified T-2 toxin per os
      for 21 days (3x2 factorial design). Four of the 7 heifers were fed 9 mg/day (25
      ug/kg) of the same purified T-2 toxin for 20 days while 3 remained untreated. The
      estrus cycles in all animals were synchronized prior to the trials and the T-2
      exposure was started in the mid-luteal phase. The acidic condition in the rumen
      was estimated by the determination of urinary net acid-base excretion. The
      ovarian activity was followed with blood sampling for progesterone on alternate
      days (Trial 1) or with ultrasonography and sampling for progesterone daily (Trial
      2). All of the heifers and concentrate-fed ewes showed a compensated acidosis,
      during first two thirds of T-2 exposure. In Trial 1, ovarian malfunction
      manifested as lower P4 peak concentration in the midluteal phase, shortening of
      the CL lifespan and prolonged follicular phases. These malfunctions were detected
      in 3 and 3 ewes fed concentrate and 0.3 mg and 0.9 mg T-2 toxin. Lower P4 peak
      concentration was observed in 1 ewe fed regular diet and 0.9 mg T-2 toxin. None
      of the control and acidotic groups (0 mg T-2), or ewes fed regular diet with 0.3
      mg T-2 showed any ovarian malfunction. In Trial 2, after PGF2, administration the
      ovulation occured later and the plasma progesterone level remained low (< 3
      nmol/l) for a longer period in T-2 treated heifers, than their untreated control
      mates (5.0+/-0.7 vs 3.7+/-0.5 d, P<0.05 and 8.3+/-0.4 vs 6.3+/-0.9 d, P<0.01,
      respectively). These results show that the peroral T-2 intake can significantly
      retard the folliculus maturation and ovulation and perhaps the subsequent
      luteinisation also in ruminants kept on concentrate-rich diet.

PMID- 10883850
TI  - Effects of transport container and ambient storage temperature on motion
      characteristics of equine spermatozoa.
AB  - This study was conducted to compare the cooling rates and storage temperatures
      within equine semen transport containers exposed to different ambient
      temperatures, and to evaluate the ability of these containers to preserve
      spermatozoal motility following 24 h of storage under these conditions. In
      Experiment 1, nonfat dried milk solids, glucose, sucrose, equine semen extender
      was divided into seven 40-mL aliquots and loaded into seven different semen
      transport containers: Equitainer I, Equitainer II, Equitainer III, ExpectaFoal,
      Bio-Flite, Lane STS, and Equine Express. After containers were loaded, they were
      subjected to one of three ambient storage temperatures: 1) 22 degrees C for 72 h,
      2) -20 degrees C for 6 h followed by 22 degrees C for 66 h, or 3) 37 degrees C
      for 72 h. Cooling rates and storage temperatures of semen extender in each
      container were monitored with thermocouples and a chart recorder. In Experiment
      2, semen from each of three stallions (3 ejaculates per stallion) was diluted to
      25 x 10(6) spermatozoa/mL with semen extender, divided into 40 mL aliquots and
      loaded into transport containers as in Experiment I. Containers were subjected to
      one of three ambient storage conditions: 1) 22 degrees C for 24 h, 2) -20 degrees
      C for 6 h, followed by 22 degrees C for 18 h, or 3) 37 degrees C for 24 h. After
      24 h of storage, spermatozoal motion characteristics (percentage of motile
      spermatozoa; MOT, percentage of progressively motile spermatozoa; PMOT, and mean
      curvilinear velocity; VCL) were evaluated using a computerized spermatozoal
      motion analyzer. Significant interactions were detected among storage conditions
      and semen transport containers for the majority of the temperature endpoints
      measured. When exposed to temporary ambient freezing conditions, the lowest
      temperatures attained by samples in containers ranged from -2.8 to 0.8 degrees C.
      Lowest temperature samples attained was not correlated (P > 0.05) with
      spermatozoal motility under any ambient condition. However, time below 4 degrees
      C was highly correlated (P < 0.05) with a reduction in spermatozoal motility.
      Mean cooling rates from 20 degrees C to 8 degrees C did not correlate with
      spermatozoal motility, except when containers were exposed to temporary freezing
      conditions. No container cooled samples below 6 degrees C in 22 degrees C or 37
      degrees C environments except for the ExpectaFoal, in which samples fell below 4
      degrees C under all ambient conditions. Ambient temperature affected MOT, PMOT
      and VCL of semen stored in all containers (P < 0.05) except for the Equitainer II
      in which motion characteristics remained high and were similar among all ambient
      temperatures (P > 0.05). Results suggest that stallion semen may be able to
      tolerate a wider range of cooling rates and storage temperatures than previously
      considered safe.

PMID- 10883851
TI  - Importance of inseminating only cows in estrus.
AB  - Reproductive efficiency is a key component in successful dairy farm management. A
      study was initiated to evaluate the incidence and consequences of inseminating
      dairy cows in the middle of the estrous cycle or while pregnant. In a research
      herd of 242 Holsteins, managed for reproduction under typical farm conditions,
      milk progesterone (P4) was assayed 3 times per wk for at least 120 d postpartum.
      The P4 cycle was compared with the estrus detection and breeding records and
      pregnancy diagnosis 6 wk after insemination. About 19% of the inseminations were
      performed when P4 was high in the estrous cycle and in pregnant cows.
      Insemination of pregnant cows led to an estimated 17% induced embryonic death or
      abortion. In Israel, inseminators are extensively trained to detect cows not in
      estrus. They reject about 16% of the cows submitted for reinsemination, with a
      95% accuracy of rejection of 44% of the cows that were pregnant. The pattern of
      submission of cows for reinsemination in areas around New York State was similar
      to Israel and to the experimental herd. These results indicate that more careful
      submission and rejection can reduce the unnecessary use of semen, reduce
      abortions and minimize long calving intervals, all contributing to the success of
      a dairy herd operation.

PMID- 10883852
TI  - Effect of lipid polarization by centrifugation at different developmental stages
      on post-thaw survival of bovine in vitro produced 16-cell embryos.
AB  - The developmental rate to the blastocyst stage of frozen-thawed bovine in vitro
      produced embryos at stages earlier than Day 6 morula is not sufficiently high for
      practical utilization. The present study was undertaken to determine the effect
      of polarization of lipid droplets in the cytoplasm of bovine in vitro produced
      embryos from zygotes to the 8-cell stage, by centrifugation without following
      micromanipulation, on the survival rate of Day 4 16-cell embryos. After
      centrifugation at 15,500 x g in medium containing cytochalasin D, embryos were
      cultured to the 16-cell stage, classified as either mostly or partially
      delipidated by degree of lipid droplet removal, and then frozen. Embryos
      centrifuged at the 2-cell stage developed to the 16-cell stage similarly to those
      centrifuged at the 8-cell stage. The developmental rate to blastocysts after
      freezing of the mostly delipidated 16-cell embryos centrifuged at the 2-cell
      stage was higher than that of those centrifuged at the zygote stage, those that
      were partially delipidated at the 2-cell stage, and those that were not
      centrifuged. The results demonstrate that polarization of lipid droplets at the 2
      cell stage by centrifugation without micromanipulation improved the survival rate
      of mostly delipidated 16-cell embryos after freezing.

PMID- 10883853
TI  - Companionship and cooperation: key themes at the world congress in Amsterdam.

PMID- 10883854
TI  - Assessment of defined antigens for the diagnosis of bovine tuberculosis in skin
      test-reactor cattle.
AB  - The continued use of purified protein derivative (PPD) tuberculin is considered
      to be the main factor which limits the specificity of diagnostic tests for bovine
      tuberculosis (TB). This study evaluated a whole blood interferon-gamma (IFN
      gamma) assay and compared the diagnostic potential of PPD with two tuberculosis
      specific antigens, ESAT-6 and MPB70. To provide estimates of sensitivity and
      specificity, responses were measured in 180 skin test-reacting cattle, of which
      131 were confirmed as tuberculous, and in 128 cattle from TB-free herds. For the
      skin test reactors, there was a positive correlation between the IFN-gamma
      responses to PPD from Mycobacterium bovis (PPDB) and PPD from Mycobacterium avium
      (PPDA), indicating cross-reactivity between these complex antigens which are the
      basis of the skin test. In comparisons of the ESAT-6 IFN-gamma test with a PPD
      IFN-gamma test (using PPDB compared with PPDA), there was a decrease in
      sensitivity (76.3 per cent vs 89.3 per cent), but a clear increase in specificity
      (99.2 per cent vs 92.2 per cent). The provision of high specificity, even with
      lower sensitivity, offers major benefits for testing in areas with a low
      incidence of TB.

PMID- 10883855
TI  - Similarity of avian paramyxovirus serotype 1 isolates of low virulence for
      chickens obtained from contaminated poultry vaccines and from poultry flocks.
AB  - At present Denmark has the status of a 'non-vaccinating' country for Newcastle
      disease and its poultry population should therefore be free of antibodies to
      avian paramyxovirus 1 (APMV-1). Three live avian vaccines against infectious
      bronchitis, avian encephalomyelitis, and chick anaemia which had been found to be
      contaminated with APMV-1 viruses of low virulence for chickens were examined. The
      vaccines were produced by the same company and the affected batches had been used
      in Denmark in 1996/97. Furthermore, APMV-1 isolates of low virulence were
      obtained from three commercial broiler breeder flocks, one of which had been
      vaccinated with two of the contaminated vaccines. The flocks belonged to the same
      hatchery organisation. A comparison of viral F0 gene sequences and typing of
      virus isolates with a panel of monoclonal antibodies showed that the vaccine and
      field isolates were identical.

PMID- 10883856
TI  - Effects of the dose of Ehrlichia phagocytophila on the severity of experimental
      infections in lambs.
AB  - Twenty-one lambs were used to investigate whether their response to an infection
      with Ehrlichia phagocytophila was dose-dependent Four groups of four lambs were
      infected intravenously with a dilution in physiological saline of E
      phagocytophila-infected sheep blood containing either 1.3 x 10(5) infected cells,
      or approximately 43 infected cells, 4.3 infected cells, or 1.3 infected cells
      (mean values) and four lambs were left uninfected. The incubation period was
      significantly shorter in the lambs infected with the highest dose of E
      phagocytophila. However, the clinical and haematological changes observed, and
      the weekly weight gains of the lambs were independent of the dose of E
      phagocytophila. As little as one Ephagocytophila infected cell may be enough to
      transmit the infection.

PMID- 10883857
TI  - Prepartum equine rotavirus vaccination inducing strong specific IgG in mammary
      secretions.

PMID- 10883858
TI  - Caprine Paramphistomum daubneyi (Trematoda) infection in Europe.

PMID- 10883859
TI  - Haematological parameters in postweaning multisystemic wasting syndrome-affected
      pigs.

PMID- 10883860
TI  - Lymphoid leukosis in an ostrich (Struthio camelus).

PMID- 10883861
TI  - Certificate in veterinary dermatology.

PMID- 10883862
TI  - TB and animal husbandry.

PMID- 10883863
TI  - CPD provision taken for granted?

PMID- 10883864
TI  - Suspected keratitis sicca in a Syrian hamster.

PMID- 10883865
TI  - Association of Veterinary Emergency Clinics.

PMID- 10883866
TI  - The periodontal abscess: a review.
AB  - BACKGROUND/AIMS: The periodontal abscess is a frequent periodontal condition in
      which periodontal tissues may be rapidly destroyed. Its importance is based on
      the possible need of urgent care, the affectation of tooth prognosis, and the
      possibility of infection spreading. There is scant information in the scientific
      literature regarding this condition and most of it has been published as case
      reports and text books, where conclusions are not evidence-based, but rather
      empirical observations made by recognised clinicians. The aim of this review was
      to critically analyse all available information on this subject in the dental and
      medical literature, including information on its prevalence, proposed etiologies
      and pathogenesis, diagnosis, microbiology and treatment alternatives. SUMMARY:
      The periodontal abscess is the 3rd most frequent dental emergency, and it is
      specially prevalent among untreated periodontal patients and periodontal patients
      during maintenance. Different etiologies have been proposed, and 2 main groups
      can be distinguished, depending on its relation with periodontal pockets. In the
      case of a periodontitis-related abscess, the condition may appear as an
      exacerbation of a non-treated periodontitis or during the course of periodontal
      therapy. In non-periodontitis related abscesses, impaction of foreign objects,
      and radicular abnormalities are the 2 main causes. The abscess microflora seems
      to be similar to that of adult periodontitis, and it is dominated by gram
      negative anaerobic rods, including well-known periodontal pathogens.
      Complications and consequences include tooth loss and the spread of the infection
      to other body sites. Diagnosis and treatment is mainly based on empiricism, since
      evidence-based data are not available. The role of systemic antibiotics, in the
      treatment of periodontal abscesses, is especially controversial.

PMID- 10883867
TI  - The periodontal abscess (I). Clinical and microbiological findings.
AB  - BACKGROUND/AIMS: Little information is available regarding the diagnosis and
      microbiology of periodontal abscesses. The aim of this descriptive clinical and
      microbiological study was to provide more information in order to help in the
      characterisation of the periodontal abscess associated to periodontitis. METHOD:
      29 consecutive patients with a periodontal abscess were studied by the assessment
      of clinical variables, including both subjective (pain, edema, redness and
      swelling) and objective (bleeding on probing, suppuration, probing pocket depth,
      tooth mobility and cervical lymphadenopathy) parameters. Microbiological samples
      were taken for anaerobic microbiology and processed by means of culture. Systemic
      involvement was also studied through the analysis of blood and urine samples
      using conventional laboratory standards. RESULTS: 62% of the abscesses affected
      untreated periodontitis patients, and 69% were associated with a molar tooth.
      More than 75% of the abscesses had moderate-severe scores related to edema,
      redness and swelling, and 90% of the patients reported pain. Bleeding occurred in
      all abscesses, while suppuration on sampling was detected in 66%. Mean associated
      pocket depth was 7.28 mm, and 79% of teeth presented some degree of mobility.
      Cervical lymphadenopathy was seen in 10% of patients, while elevated leucocyte
      counts were observed in 31.6%. The absolute number of neutrophils was elevated in
      42% of the patients. High prevalences of putative periodontal pathogens were
      found, including Fusobacterium nucleatum, Peptostreptococcus micros,
      Porphyromonas gingivalis, Prevotella intermedia and Bacteroides forsythus.
      CONCLUSIONS: The periodontal abscess has clear clinical characteristics and is
      usually associated with severe periodontal destruction. This condition may cause
      systemic involvement and the lesion generally has a large bacterial mass with a
      high prevalence of well-recognised periodontal pathogens.

PMID- 10883869
TI  - Relation of motility of subgingival microflora as a clinical parameter to
      periodontal disease status in human subjects.
AB  - BACKGROUND/AIMS: The purpose of this study was to evaluate the possible
      relationship between the motility of subgingival microflora and 5 clinical
      parameters commonly used in dental clinics. METHOD: The clinical parameters were
      pocket depth, gingival inflammation, plaque accumulation, bleeding on probing and
      pus discharge. The motility of human subgingival microflora was estimated as the
      number of pixels remaining after subtraction of serial video frames using a high
      speed shutter camera and image analysis system, and was defined as the sum of
      pixels of 10 successive subtractions per sample over a 10-s time period. RESULTS:
      The bacterial motility showed significant positive, moderate or low associations
      with the five clinical parameters. The highest correlation was observed between
      the bacterial motility and pocket depth (r=0.36, p=0.0001). Furthermore,
      clinically defined periodontal healthy and diseased sites were significantly
      different with respect to the bacterial motility (p<0.0001). To determine whether
      the bacterial motility was dependent or independent of the other clinical
      variables, the data were analyzed based on common factor analysis. Three factors
      were extracted and explained about 75% of the variance of the original 6 clinical
      parameters. Only the bacterial motility had a positive coefficient for all these
      three factors. The plot of bacterial motility was placed separately from those of
      other variables in the scatterplot of the loadings of factor 2 versus factor 1
      and factor 2 versus factor 3. CONCLUSIONS: This suggests that bacterial motility
      may be an independent variable among the clinical parameters. Taken together,
      these data indicate that bacterial motility provides unique information about the
      clinical periodontal condition and may be a useful tool for the monitoring of
      subgingival plaque in relation to periodontal disease.

PMID- 10883868
TI  - The periodontal abscess (II). Short-term clinical and microbiological efficacy of
      2 systemic antibiotic regimes.
AB  - BACKGROUND/AIMS: The aim of this short-term open parallel longitudinal clinical
      study was to compare the clinical and microbiological efficacy of 2 different
      antibiotic regimes in the treatment of acute periodontal abscesses. METHOD: After
      patient selection, a clinical examination was carried out recording the following
      variables: pain, edema, redness, swelling, bleeding on probing, suppuration,
      tooth mobility, lymphadenopathy, and probing pocket depth. Microbiological
      samples were taken from the lesion and the patient was randomly assigned to one
      of two antibiotic regimes: azithromycin or amoxicillin/clavulanate. Clinical
      variables were recorded, and microbiological samples were taken, at 3-5 days, 10
      12 days and 30 days. Additional mechanical treatment (debridement and scaling)
      was performed in the third visit (10-12 days). Blood and urine samples were
      collected at baseline and after 10-12 days. Microbiological samples were
      processed by anaerobic culturing, and isolated periodontal pathogens were tested
      for antibiotic susceptibility by means of the spiral gradient endpoint
      methodology. RESULTS: 15 patients took azithromycin, and 14
      amoxicillin/clavulanate. Subjective clinical variables demonstrated statistically
      significant improvements with both antibiotic regimes, which lasted for at least
      1 month (p<0.01). Objective clinical variables also showed clear improvements,
      being statistically significant after 30 days with probing pocket depth in the
      azithromycin group (p<0.01). Microbiologically, short-term reductions were
      detected with both antibiotics, however fast recolonization occurred after the
      third visit. No significant differences were found between both treatment
      regimes. Antibiotic susceptibilities demonstrated no resistances for
      amoxicillin/clavulanate, while 2-3 strains of each studied pathogen were
      resistant to azithromycin. CONCLUSIONS: However, both antibiotic regimes were
      effective in the short-term treatment of periodontal abscesses in periodontitis
      patients.

PMID- 10883870
TI  - The validity and reproducibility of an oral rating index as a measurement of
      gingival health care and oral hygiene level in adults.
AB  - The purpose of this study was to investigate the validity and reproducibility of
      an oral rating index (ORI) as a conceptual measurement of "gingival health care"
      level in adults. The study was conducted on 163 patients who received medical
      examinations and attended for dental checkups at a hospital. The score of the ORI
      was recorded as excellent (+2), good (+ 1), questionable (0), poor (-1) or very
      poor (-2). The validity of the ORI was investigated by comparing it with:
      Jackson's gingivitis index (GI); Greene & Vermillion's debris index (DI) and
      calculus index (CI); probing pocket depth (PPD); and percentage of bleeding on
      probing (%BOP). The intra- and inter-examiner reproducibility of the ORI was
      assessed on a flat screen using patients' color transparencies of the mouth. The
      ORI had significantly negative correlations with the GI, DI, CI, and PPD
      (p<0.001). The K values were 0.604-0.672 for intra-examiner reproducibility, and
      0.441-0.449 for inter-examiner reproducibility. The present study suggests that
      the ORI has moderate to good intra-examiner and inter-examiner reproducibility.
      Mouth examination using the ORI appears to provide useful information that will
      enable a dental professional or health educator to make sensible decisions on the
      type and level of oral health instruction according to adults' gingival health
      care level.

PMID- 10883871
TI  - Microbial comparison of smoker and non-smoker adult and early-onset periodontitis
      patients by polymerase chain reaction.
AB  - A number of bacterial species are involved in the aetiology of periodontitis and
      include Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis,
      Prevotella intermedia, Bacteroides forsythus and Treponema denticola. Several
      studies have shown differences in the microflora between the various forms of
      periodontal disease. It is recognised that smoking is a risk factor for
      periodontal disease, but there are conflicting reports on whether or not smoking
      has an effect on the periodontal microflora. We utilised the polymerase chain
      reaction to determine the presence of A. actinomycetemcomitans, P. gingivalis, P.
      intermedia, B. forsythus and T. denticola in subgingival plaque samples in 33
      adult periodontitis (AP) patients and 24 generalized early-onset periodontitis
      (GEOP) patients prior to treatment. When GEOP and AP patients were compared there
      were significant differences in the number of positive patients and sites for
      both A. actinomycetemcomitans and B. forsythus (p=0.0023 and 0.00001,
      respectively). No statistically significant differences in the prevalence of
      these organisms were found between smoker and non-smoker groups. These results
      confirm that AP and GEOP sites harbour varied microflora, but show that B.
      forsythus and A. actinomycetemcomitans were detected to a significantly greater
      extent in this group of GEOP than in the AP patients investigated. Our findings
      do not support the hypothesis that smokers have significant differences in the
      prevalence of periodontal pathogens from non-smokers.

PMID- 10883872
TI  - Chlorhexidine spray versus chlorhexidine mouthwash in the control of dental
      plaque after periodontal surgery.
AB  - BACKGROUND/AIMS: This clinical trial aimed at comparing 2 different means of
      delivering chlorhexidine digluconate (CHX) in the oral hygiene phase during the 2
      weeks following periodontal surgery. METHOD: 40 patients were randomly divided
      into 2 groups: A (using CHX mouthwash) and B (using CHX spray). Professional oral
      hygiene was carried out immediately before surgical operation. For 7 days after
      surgery, group A used CHX mouthwash and group B CHX spray on the teeth involved
      in the surgical procedure, while mechanical oral hygiene was maintained only on
      the teeth not involved surgically. After suture removal, on the 7th day, patients
      were allowed to perform mechanical oral hygiene also on surgical sites. Plaque
      index (PI) and stain index (SI) were evaluated on the 7th and 14th days after the
      operation. RESULTS: In both groups, PI increased similarly with respect to the
      baseline in surgically involved teeth, being 0.25+/-0.41 (SD) and 0.15+/-0.26,
      respectively, in A and B, on day 7, and 0.14+/-0.23 (A) and 0.10+/-0.22 (B), on
      day 14. There was no significant difference between A and B on either day 7 or
      14. On the contrary, SI increased significantly in respect to the baseline over
      the 14 days in group A at both involved and not involved sites, while it did not
      differ from the baseline in group B. CONCLUSIONS: The present results indicate
      that the efficacy of CHX spray in the post-surgical control of dental plaque is
      not different from that of CHX mouthwash. Tooth staining, on the contrary, was
      significantly lower in the group using CHX spray. The observed effects might be
      related to the way of delivering CHX and to the total dose administered, about
      80% lower in group B in respect to A. Further studies are needed to validate the
      preliminary findings of the present study.

PMID- 10883873
TI  - Thickness of masticatory mucosa.
AB  - BACKGROUND: The aim of the present study was to assess thickness of all parts of
      the masticatory mucosa by using an ultrasonic measuring device. METHODS: A total
      of 40 periodontally healthy subjects, 19 to 30 years old, took part. Thickness of
      masticatory mucosa was measured at a maximum of 149 sites in each proband.
      RESULTS: Female volunteers had significantly thinner mean masticatory mucosa than
      males (p<0.01). Mean thickness of facial gingiva ranged between 0.7 mm at canines
      in the maxilla and central incisors in the mandible and 2.3 mm at 3rd molars in
      the mandible. In the mandible, thickness of lingual gingiva ranged between 0.9 mm
      at lateral incisors and 2.3 mm at 3rd molars. Interdental gingiva ranged between
      1.0 mm 2.1 mm. With 3 mm or more, on average, palatal masticatory mucosa was
      thickest in the 3rd molar region and at 2nd premolars at more central locations.
      2 regions with comparatively thin palatal mucosa of about 2 mm were identified,
      namely (i) at central and lateral incisors and (ii) at the prominence of the
      palatal roots of 1st and 2nd molars. The thickest tissue with more than 4 mm, on
      average, was observed in the tuberosity and retromolar regions. CONCLUSIONS:
      Considerable intra- as well as interindividual variation of thickness of
      masticatory mucosa could be observed. According to differences in thickness of
      facial and interdental gingiva, it appears that lining is also an important
      function of the gingiva in reducing and smoothing the pronounced convexities of
      the dentoalveolar, i.e., skeletal, complex.

PMID- 10883874
TI  - PCR monitoring for tetracycline resistance genes in subgingival plaque following
      site-specific periodontal therapy. A preliminary report.
AB  - BACKGROUND: The selection of antibiotic resistance genes during antibiotic
      therapy is a critical problem complicated by the transmission of resistance genes
      to previously sensitive strains via conjugative plasmids and transposons and by
      the transfer of resistance genes between gram-positive and gram-negative
      bacteria. The purpose of this investigation was to monitor the presence of
      selected tetracycline resistance genes in subgingival plaque during site specific
      tetracycline fiber therapy in 10 patients with adult periodontitis. METHOD: The
      polymerase chain reaction (PCR) was used in separate tests for the presence of 3
      tetracycline resistance genes (tetM, tetO and tetQ) in DNA purified from
      subgingival plaque samples. Samples were collected at baseline, i.e., immediately
      prior to treatment, and at 2 weeks, and 1, 3, and 6 months post-fiber placement.
      The baseline and 6-month samples were also subjected to DNA hybridization tests
      for the presence of 8 putative periodontal pathogenic bacteria. RESULTS: PCR
      analysis for the tetM resistance gene showed little or no change in 5 patients
      and a decrease in detectability in the remaining 5 patients over the 6 months
      following tetracycline fiber placement. The results for tetO and tetQ were
      variable showing either no change in detectability from baseline through the 6
      month sampling interval or a slight increase in detectability over time in 4 of
      the 10 patients. DNA hybridization analysis showed reductions to unmeasurable
      levels of the putative periodontal pathogenic bacteria in all but 2 of the 10
      patients. CONCLUSIONS: These results complement earlier studies of tet resistance
      and demonstrate the efficacy of PCR monitoring for the appearance of specific
      resistance genes during and after antibiotic therapy.

PMID- 10883875
TI  - Topical metronidazole application as an adjunct to scaling and root planing.
AB  - AIM: This study was carried out to investigate the effect of 2 applications of a
      metronidazole 25% dental gel as adjunctive therapy to subgingival scaling with
      root planing. METHOD: 59 of the original collective of 64 patients with adult
      periodontitis were observed for a 9-month period. This randomised single-blind
      study was carried out in split-mouth design. Each patient had to have at least 2
      pockets with a probing depth of > or =5 mm in each quadrant. The clinical
      parameters, pocket probing depth (PPD), attachment level (AL) and bleeding on
      probing (BOP), were recorded at all teeth on days 0, 91, 175 and 259; in
      addition, subgingival plaque samples taken from 45 patients were analysed by
      means of dark-field microscopy. Therapy comprised subgingival scaling and root
      planing (SRP) of all quadrants and additional application of metronidazole 25%,
      dental gel in 2 randomly selected quadrants (SRP+Metro). Treatment was confined
      to teeth with a baseline PPD of > or =5 mm. Average PPD and AL and the incidence
      of BOP were computed for all pockets with a baseline PPD of > or =5 mm, and the 2
      methods compared. The main efficacy variable for evaluation of the 2 treatments
      was the difference in PPD on day 259. RESULTS: Comparison of the 2 treatments
      revealed a statistically significant improvement in the clinical parameters for
      both treatment methods over the study period. Between baseline and day 259,
      significant differences in PPD (SRP+Metro: from 6.00 to 4.63 mm, SRP: from 6.02
      to 4.83 mm) and BOP (SRP+Metro: from 67 to 31%, SRP: from 64 to 36%) were
      observed between the 2 treatment groups. Evaluation according to different
      patient groups demonstrated significant advantages of the combined therapy in
      previously-untreated patients, especially in female probands. Dark-field
      microscopy revealed a shift in the bacterial flora towards "healthy conditions".
      CONCLUSIONS: The results show that only minor advantages are to be gained from
      the application of a metronidazole 25% dental gel as adjunctive therapy to
      subgingival scaling. The distinctly better results of combined therapy in
      previously-untreated patients calls for more thorough investigation.

PMID- 10883876
TI  - Empirical analysis of the selective attention and associated behavior checklists
      of the Aggregate neurobehavioral student health and educational review.
AB  - For 111 referred children, the Behavior Observation (BO) and the Selective
      Attention (SA) components of the Aggregate Neurobehavioral Student Health and
      Educational Review (ANSER) were completed by mothers and teachers and the
      Pediatric Examination of Educational Readiness at Middle Childhood was completed
      by the pediatrician. Smaller samples were used to study concurrent validity. The
      questionnaires presented high internal reliability. Factor analyses of the BO
      questionnaires resulted in a common primary factor of "Aggressiveness" for
      ratings by mothers and teachers. For the SA, "Hyperactivity" (mothers) and
      "Inattention" (teachers) accounted for the majority of variance. There were
      modest correlations between teachers and mothers. The correlation between the
      pediatrician and teachers reached the highest value. The BO-Teachers form was
      significantly related to the Teacher Report Form and the Conners Teacher Rating
      Scale. The authors concluded that the ANSER presents concurrent validity for
      teacher ratings, items predictive of atypical behavior, and a unique pool for
      defining a subgroup of children with attentional disorders. The limited
      relationship between mothers and teachers may be ascribed to different
      interpretations of the same items.

PMID- 10883877
TI  - Hypothyroxinemia of prematurity and infant neurodevelopment: a pilot study.
AB  - To assess whether hypothyroxinemia has specific effects on neurodevelopment in
      premature infants, thyroid hormone levels were determined at 2 weeks of life and
      40 weeks postconceptional age (PCA), and infants were evaluated at 3 months
      corrected age using the Bayley Scales of Infant Development and Early Infancy
      Temperament Questionnaire. Additional attention scales were derived from the
      factor analysis of relevant Bayley items. Fifteen infants born between 30 and 35
      weeks and 21 full-term infants were studied. Results indicated no group
      differences on the Bayley or derived attention scales, whereas the temperament
      questionnaire revealed lower sensory thresholds and greater reactivity in the
      preterm group. The preterm group had normal thyroxine (T4) levels at 2 weeks of
      age, which declined by 40 weeks PCA for both free T4 (p < .01 for reference value
      and p < .0001 for gestational age-adjusted value) and total T4 (p < .05 for age
      adjusted value). Correlations revealed that higher 40-week PCA free T4 levels
      were associated with better attentiveness ratings (p < .01 for reference and p <
      .0001 for gestational-age values) and sustained attention (p < .05) and higher 40
      week total T4 with better motor skills (p < .05 for gestational-age value). These
      findings signify that a mild degree of hypothyroxinemia is evident in preterm
      infants without neurological risk and predicts subsequently poorer cognitive and
      motor abilities.

PMID- 10883878
TI  - Effects of prenatal tobacco exposure on preschoolers' behavior.
AB  - This is a longitudinal study of the relationship between prenatal tobacco
      exposure and the development of behavior problems in 672 children at the age of 3
      years. Women from a prenatal clinic were interviewed about substance use at the
      end of each trimester of their pregnancy and at 3 years postpartum. Children were
      assessed at the age of 3 years with maternal ratings of behavior problems,
      activity, and attention. The prevalence of tobacco use was high in this cohort;
      54.3% and 52.3% of the women smoked tobacco in the first and third trimesters of
      pregnancy, respectively. At 3 years postpartum, 61.6% of the women were smokers.
      There were significant effects of prenatal tobacco exposure on the children's
      behavior at age 3 years. Increases in scores on the Oppositional Behavior,
      Immaturity, Emotional Instability, Physical Aggression, and Activity scales and
      in the total score on the Toddler Behavior Checklist (TBC) were significantly
      associated with prenatal tobacco exposure. Smoking one pack of tobacco cigarettes
      per day during the third trimester of pregnancy was associated with an increase
      of 6 points in the total problem behavior score. Among the subscales of the TBC,
      tobacco exposure had the largest effect on oppositional behavior. Impulsivity and
      peer problems were associated with both prenatal and current tobacco exposure.
      Only current tobacco exposure predicted attention problems. Prenatal tobacco
      exposure had a significant negative effect on the development of behavior
      problems among preschoolers.

PMID- 10883879
TI  - Psychological adjustment and coping in a population of children with recurrent
      syncope.
AB  - The authors examined the association of psychological adjustment, styles of
      coping, and disease severity for children with recurrent syncope. Participants
      were 44 children and adolescents with a history of recurrent syncope and 40
      healthy comparison control children. Dependent variables were measures of
      internalizing adjustment (e.g., anxiety, depression, withdrawal) reported by
      children and their parents and styles of coping reported by children. Parents
      reported higher frequencies of the internalizing of behavioral symptoms (i.e.,
      anxiety, withdrawal) for children with recurrent syncope compared with their
      healthy counterparts. Children's self-reports did not reveal significant
      differences between the syncope and comparison groups in psychological adjustment
      and styles of coping. The authors conclude from these findings that adjustment
      difficulties, including symptoms of anxiety and social withdrawal, may occur with
      recurrent syncope. Implications for clinical practice and future research are
      discussed.

PMID- 10883880
TI  - Do psychosocial variables predict the physical growth of infants with orofacial
      clefts?
AB  - This study sought to determine whether psychosocial variables (parent-infant
      feeding interactions, infant temperament, maternal social support, family
      socioeconomic status) are important in predicting the physical growth of infants
      with orofacial clefts, after controlling for selected medical variables (infant
      health status, cleft diagnosis, and previous weight). Infant growth (weight-to
      height zscores) was tracked for 2 years, and models were developed to predict
      growth at 3, 12, and 24 months. The authors also examined the growth trajectories
      of infants with different cleft types: cleft lip and palate (CLP) and cleft
      palate only (CPO). CPO infants showed some increase in their growth relative to
      the population mean over time, whereas the growth of CLP infants remained lower
      than the population mean at all time points. After controlling for medical
      variables, psychosocial variables collectively accounted for an additional 42% of
      the variance in infants' growth at 3 months of age, but they did not account for
      growth at 12 months and 24 months, largely due to the strong effect of previous
      growth. The authors tentatively conclude that psychosocial variables influence
      the early growth trajectory of infants with clefts, but subsequent growth becomes
      increasingly regulated by biological factors.

PMID- 10883882
TI  - Estimates of temperament are easy; accurate measurements take a little longer.

PMID- 10883881
TI  - Measuring difficult temperament the easy way.
AB  - In this study, the authors introduce a new measure of infant temperament, the
      Pictorial Assessment of Temperament (PAT), and provide information about its
      psychometric qualities based on findings from a study of 132 mothers and infants.
      The PAT is a 10-item measure of "difficult" temperament that is quick and easy to
      use and avoids some of the inherent problems in existing paper-and-pencil
      measures of temperament (e.g., complexity of response choices, dependence on
      respondents' educational level and verbal skills). It has convergent validity
      with the Revised Infant Temperament Questionnaire and with observed behavior in a
      laboratory procedure, moderate reliability and stability over time, and moderate
      agreement between mothers' and fathers' reports. Predictive validity was
      demonstrated by significant associations with the children's later disruptive
      behavior, behavior problems, lack of sociability, and negativity in interactions
      with their mother. Parent characteristics (agreeableness, extraversion,
      neuroticism, sensitivity, depression) were not related to scores on the PAT,
      demonstrating its discriminant validity.

PMID- 10883883
TI  - Temper tantrums, impulsivity, and aggression in a preschool-aged boy.

PMID- 10883884
TI  - Disturbances of attachment in young children adopted from institutions.
AB  - In this article, the author describes a discrepancy between popular media
      accounts of reactive attachment disorder (RAD) and its clinical and scientific
      description. The literature on serious disturbances of attachment in children
      adopted out of institutions is reviewed. The author concludes that children
      adopted from institutions are at dramatically increased risk for disturbances,
      although the majority of such children do not demonstrate problems. Both the
      duration of deprivation and the postinstitutional caregiving environment seem to
      be importantly related to outcome. Inhibited/withdrawn RAD is exceedingly
      uncommon in children adopted from institutions (at least after 1 or more years),
      but disinhibited/indiscriminate RAD is quite persistent. Long after children
      become attached to adoptive parents, a number of them continue to exhibit
      indiscriminate sociability. Three explanations for this divergence of recovery
      curves are considered. It is likely that future systematic studies will
      illuminate many areas that are unclear at this time.

PMID- 10883885
TI  - A lysosomal pepstatin-insensitive proteinase as a novel biomarker for breast
      carcinoma.
AB  - Lysosomal proteinases play an important role in the turnover of intracellular
      proteins, and acidic proteinases such as cathepsin D are known to be increased in
      breast carcinoma. In the present study the activity of a newly discovered acidic
      lysosomal pepstatin-insensitive proteinase (CLN2p) was measured in breast tissues
      by the most sensitive and highly specific assay that we had developed for the
      diagnosis of late-infantile neuronal ceroid lipofuscinosis (LINCL) (2). Samples
      from eight normal subjects undergoing reductive mammoplasty and 200 patients with
      primary breast carcinoma were analyzed. The results suggest a two- to seventeen
      fold higher CLN2p activity in tumors, which was significantly and positively
      correlated with already known breast cancer biomarkers such as levels of
      cathepsin D, estrogen receptor and progesterone receptor. These results suggest a
      diagnostic and prognostic potential for this novel acid proteinase in breast
      cancer.

PMID- 10883886
TI  - Is adjuvant tamoxifen recommended in post-menopausal node-negative breast cancer
      patients with high estrogen receptor values?
AB  - The impact of ER levels on the response to tamoxifen was evaluated in 1,623
      postmenopausal primary breast cancer patients treated at our center (median
      follow-up 8.2 years). In patients receiving adjuvant tamoxifen a significantly
      longer disease-free survival (DFS) was observed when ER levels were elevated
      (p<0.00001). Very high ER (>424 fmol/mg protein) appeared to be detrimental in
      node-negative patients not treated with tamoxifen.

PMID- 10883887
TI  - The clinical significance of thymidine kinase 1 measurement in serum of breast
      cancer patients using anti-TK1 antibody.
AB  - The activity of total thymidine kinase in serum (S-TK) has been used as a tumor
      maker for decades. To date such activity has been determined using [125]I-iodo
      deoxyuridine as a substrate. The aim of this study was to develop a new, antibody
      based technique for the measurement of cytoplasmic thymidine kinase (TK1) in
      serum. Both mono- and polyclonal antibodies against S-TK1 were used in dot blot
      assay. S-TK1 was characterized by SDS and IEF techniques. Sixty-five breast
      cancer patients were studied, including 17 preoperative and 38 postoperative
      tumor-free patients and 10 patients with metastases to the lymph nodes (N1-2).
      They were compared to patients with benign tumors (n=21) and healthy volunteers
      (n=11). S-TK1 was low (0-1.0 pM) in healthy volunteers, while in preoperative
      patients the level was increased 6-110-fold. Significant differences were
      observed between preoperative patients and healthy volunteers (p=0.005),
      preoperative patients and patients with benign tumors (p<0.001), and preoperative
      patients and postoperative patients without metastases (p<0.001). No significant
      difference was observed between preoperative patients and postoperative patients
      with metastases (p=0.191). The S-TK activity in preoperative patients was also
      high in serum, but no decrease was observed following surgery. In conclusion, the
      anti-TK1 antibody could be a good marker for monitoring the response of breast
      cancer patients to therapy.

PMID- 10883888
TI  - Prognostic value of CA125 kinetics and half-life in advanced ovarian cancer.
AB  - This retrospective study was undertaken in order to assess the prognostic value
      of prechemotherapy serum CA125 level, CA125 kinetics, and CA125 half-life
      compared to the ten common clinicopathological variables in patients with
      advanced ovarian cancer (AOC). CA125 serum levels were determined before and
      during induction cisplatin polychemotherapy in 222 patients. A prechemotherapy
      CA125 level higher than 35 U/mL was found in 134 patients. Blood samples were
      further obtained before each course of chemotherapy (CT). CA125 half-life values
      were calculated in 112 patients with CA125 levels above 60 U/mL using van der
      Burg's exponential regression model. The prechemotherapy CA125 level had no
      prognostic value for survival. However, the median survival time of patients with
      CA125 levels below the upper normal limit of normality after two courses of CT
      was 101 months compared to a median survival of 21 months in patients without
      CA125 normalization (p=0.0000). Half-life calculation showed a significant
      correlation with survival. The median survival times of patients with T1/2 <20
      days and T1/2 >20 days were 101+ and 18 months, respectively (p=0.0003). In a
      survival analysis using the Cox proportional hazard model, independent prognostic
      variables for survival included therapeutic response (p<0.0001), Karnofsky index
      (p<0.0001), residual disease (p<0.0001), tumor grade (p=0.0002), CA125 half-life
      (p=0.007), and CA125 kinetics (p=0.04). As a consequence, the possibility to
      predict treatment response by the CA125 half-life during chemotherapy and the
      time needed for normalization of CA125 levels can divide patients into good and
      poor prognostic groups early during chemotherapy.

PMID- 10883889
TI  - Optimizing efficacy of quick parathyroid hormone determination in the operating
      theater.
AB  - The usefulness of intraoperative parathyroid hormone (PTH) monitoring has been
      extensively documented in primary hyperparathyroidism (HPT), whereas few data
      have been published on its use in reoperations or in secondary and tertiary HPT.
      We report our initial experience with a rapid (12 min response) PTH
      immunochemiluminometric assay performed in the operating room during surgery in
      12 patients with primary HPT, 16 end-stage renal disease patients with secondary
      HPT and five kidney transplanted subjects with tertiary HPT. Blood samples were
      taken at baseline, within 10 min after resection and subsequently at various
      intervals whenever needed. The mean PTH levels before and after parathyroidectomy
      were 230.5 pg/mL (range 69-842) and 47.3 pg/mL (range 5-184), respectively, in
      primary HPT, 855.0 pg/mL (416-1655) and 202.2 pg/mL (53-440) in secondary HPT,
      and 205.6 pg/mL (116-301) and 45.4 pg/mL (18-97) in tertiary HPT. All patients
      but one had a significant percentage decline from pre-excision values (mean
      76.9%, 76.0%, and 76.1% in primary, secondary and tertiary HPT, respectively).
      While a reduction of more than 50% was observed in 30 out of 33 patients after
      the first intraoperative sampling, additional measurements were performed in 10
      cases. On-site PTH monitoring with this user-friendly and reliable system has
      proved helpful in targeting PTH tests to give the surgeon a rapid and accurate
      assessment of the intervention. The development of optimal PTH sequence
      strategies with decision-focused analytical and clinical limits will improve the
      efficacy of "point-of-care" PTH assay and resource utilization.

PMID- 10883890
TI  - Changes in circulating dendritic cells and IL-12 in relation to the angiogenic
      factor VEGF during IL-2 immunotherapy of metastatic renal cell cancer.
AB  - Angiogenesis and immunosuppression are the main biological mechanisms responsible
      for cancer progression. Moreover, recent observations suggesting a negative
      influence of angiogenesis on anticancer immunity have shown that some angiogenic
      factors, such as VEGF, may induce immunosuppression. In addition, the evidence of
      abnormally high blood levels of VEGF has been proven to be associated with
      resistance to IL-2 immunotherapy. The present study was performed to establish a
      possible relation ship between the efficacy of IL-2 cancer immunotherapy and
      changes in circulating levels of VEGF, IL-12, mature and immature dendritic cells
      (DC). The study included 25 metastatic renal cell cancer patients who underwent
      subcutaneous low-dose IL-2 immunotherapy (6 MIU/day for 6 days/week for 4 weeks).
      Immature and mature DCs were identified as CD123+ and CD11c+ cells, respectively.
      The clinical response consisted of partial response (PR) in five, stable disease
      (SD) in 11 and progressive disease (PD) in the remaining nine patients. The mean
      IL-12 levels observed during IL-2 immunotherapy were significantly higher in
      patients with PR or SD than in those with PD, whereas the mean VEGF
      concentrations were significantly higher in patients who had PD than in those
      with PR or SD. Finally, a significant increase in the mean number of circulating
      mature DCs occurred only in patients with PR or SD, whereas no significant change
      was seen in patients with PD. By contrast, no significant change was observed in
      the mean number of immature DCs. This study shows that the efficacy of IL-2
      immunotherapy is associated with a significant increase in circulating mature DCs
      and IL-12, without any concomitant increase in VEGF concentrations. Further
      studies will be required to better define the relationship between activation of
      anticancer immunity and control of angiogenesis-related mechanisms.

PMID- 10883891
TI  - Pepsinogen C expression in tumors of extragastric origin.
AB  - We have examined by immunohistochemistry the ability of human carcinomas of
      various origin to produce pepsinogen C, an aspartyl proteinase mainly involved in
      the digestion of proteins in the stomach and recently found to be associated with
      breast carcinomas. Of the 268 tumors analyzed 80 (29.8%) showed positive staining
      for pepsinogen C. These positive tumors included 12 gastric (38.7% of the 31
      examined cases), nine pancreatic (42.8%), two renal (20%), 12 prostatic (40%),
      three bladder (27.3%), 14 endometrial (29.7%) and 18 ovarian (40%) carcinomas. We
      also detected 10 melanomas (50%) that were positive for pepsinogen C. By
      contrast, immunohistochemical staining for the proteinase was not detected in
      colorectal, cervical, lung and basal cell skin carcinomas. These results
      demonstrate that pepsinogen C, a proteolytic enzyme of highly restricted
      expression in human tissues, can also be expressed by a wide variety of human
      carcinomas. In addition, and similar to pepsinogen C expression in breast
      carcinomas, the production of this enzyme by different human tumors might be
      related to putative hormonal alterations associated with the development and
      progression of these tumors.

PMID- 10883892
TI  - Anticancer drug action on poly(A) polymerase activity and isoforms during HeLa
      and WISH cell apoptosis.
AB  - Poly(A) polymerase (PAP; EC 2.7.7.19) catalyzes mRNA polyadenylation. Its
      activity and isoform levels vary during cell cycle transformation and apoptosis.
      It has become widely accepted that cell death after DNA damage by anticancer
      agents is primarily the result of apoptosis and that cells able to evade
      apoptosis will be resistant to cell killing. The therapeutic agents interferon
      (IFN), 5-fluorouracil (5-FU) and tamoxifen (Tam) with different mechanisms of
      action mediate both partial dephosphorylation and inactivation of PAP, detected
      by immunoblotting analysis and PAP enzyme assay, respectively. We examined the
      apoptotic tendencies of HeLa and WISH cell lines caused by one of the drugs used,
      5-FU. The trend in the cells examined, observed by DAPI and/or DNA fragmentation
      assay, was found to be accompanied by and reversibly related to PAP activity
      levels and PAP lower mobility phosphorylated forms of 106 and 100 kDa isoforms.
      Moreover, a cell type-modulated, differential response of HeLa (chemosensitive
      cells) versus WISH (drug-resistant diploid cells) has been revealed. This finding
      yields information on the possible use of PAP as a tumor marker involved in cell
      commitment and/or induction of apoptosis and may help to improve our
      understanding of tumor cell sensitivity to anticancer agents.

PMID- 10883893
TI  - Use of tumor markers in the management of head and neck cancer.
AB  - Serologic tumor markers have been evaluated in the diagnosis, management and
      follow-up of patients with head and neck cancer. However, to the authors'
      knowledge no tumor marker has yet been shown to be useful for monitoring the
      response to chemotherapy in this type of disease, in particular for
      undifferentiated tumors. The pretreatment levels of CEA, TPA, SCC and ferritin
      were evaluated in 98 patients with advanced head and neck cancer. Of this group
      64 patients were studied sequentially every month during planned chemotherapy and
      three weeks after treatment using standard commercial kits. The results showed
      the following sensitivity values: TPA 50%, CEA 36%, SCC 34% and ferritin 19%. The
      incidence and magnitude of the marker elevations were correlated with the extent
      of disease. In patients with squamous cell cancer SCC and CEA were elevated (by
      68% and 54%, respectively) in tumors with good differentiation (G1), but only by
      13% (both markers) in tumors classified as poorly differentiated (G3). CEA, SCC
      and ferritin serum levels were not correlated with response to chemotherapy,
      while TPA values correlated with the clinical response to treatment in 100% of
      patients with undifferentiated cancer and in 75% of those with squamous cell
      cancer. Our data indicate that in patients with head and neck cancer TPA appears
      to be a sensitive marker, followed in decreasing order of sensitivity by CEA, SCC
      and ferritin. However, SCC and CEA seem to be the most suitable markers for
      squamous cell cancer and in particular for more differentiated tumors (G1).
      Finally, TPA has proved to be a useful marker for monitoring the response to
      chemotherapy in patients with head and neck cancer, in particular for
      undifferentiated tumors.

PMID- 10883895
TI  - CD44s, CD44v5 and CD44v6 protein contents in colorectal cancer and surrounding
      mucosa.

PMID- 10883894
TI  - EORTC Receptor and Biomarker Study Group Report: a sandwich enzyme-linked
      immunosorbent assay for vascular endothelial growth factor in blood and tumor
      tissue extracts.
AB  - A four-antibody sandwich enzyme-linked immunosorbent assay (ELISA) for vascular
      endothelial growth factor (VEGF) for application in blood (serum and plasma) and
      tumor tissue extracts was set up within the framework of the EORTC Receptor and
      Biomarker Study Group (RBSG). Polyclonal antibodies against VEGF165 were raised
      in chickens and rabbits, and used in a previously described assay format. The
      assay was validated and characterized for use in serum, plasma and tumor tissue
      extracts. The resulting VEGF ELISA was found to be specific for VEGF165 and
      VEGF121, the main isoforms of VEGF. The assay showed good precision and
      parallelism in serial dilutions of samples. The assay was not susceptible to
      interference by heterophilic antibodies because avian antibodies (duck anti
      chicken and chicken anti-VEGF) were used in the pre-analyte stage and mammalian
      antibodies (rabbit anti-VEGF and goat anti-rabbit) in the post-analyte stage. In
      conclusion, a sensitive, robust and specific VEGF ELISA has been developed.
      Research into the prognostic value of VEGF employing this assay is currently
      underway.

PMID- 10883896
TI  - Study of the expression on the CD44v5 adhesion molecule in invasive lobular
      carcinomas of the breast. Association between negativity and cellular S-phase
      fraction >7%.

PMID- 10883897
TI  - TAG-72 in gastric cancer: relationship between preoperative serum levels and
      tumoral content of the antigen.

PMID- 10883898
TI  - Central nervous system hydatidosis in Turkey: a cooperative study and literature
      survey analysis of 458 cases.
AB  - OBJECT: Hydatidosis is both a medical and an economic problem in Turkey. The aim
      of this study was to analyze central nervous system (CNS) involvement in this
      disease, the related problems the disease causes, and its diagnostic and
      therapeutic aspects. METHODS: The authors conducted an extensive literature
      survey of the subject, in which papers published by Turkish authors in
      international and domestic journals were carefully analyzed. In addition, the
      authors conducted a cooperative study in which data were gathered from 47
      neurosurgery departments across the country. The purpose was to determine the
      current status of the disease in Turkey; thus, each unit was questioned about
      their experience over the past 5 years. Contrary to common belief, the incidence
      of hydatidosis has not decreased significantly in Turkey. However, computerized
      tomography and magnetic resonance imaging have tremendously increased diagnostic
      specificity. Incidences of morbidity and mortality have improved over time,
      according to the results of the cooperative study, although these changes are not
      statistically significant. This may be attributed to experience that has been
      gained and to more frequent use of chemotherapy, as reflected by the cooperative
      study data. The two statistically significant findings of that study were
      expanded use of chemotherapy in the management of hydatidosis, and a higher rate
      of extraneural involvement in the disease. The cooperative study revealed that
      chemotherapy was being used more often and that there was a wider range of
      indications for this treatment than previously reported. The higher rate of
      extraneural involvement was predictable because lesions in the CNS are typically
      secondary in this disease. With regard to the studies' findings on cases of
      spinal hydatid cysts, the authors found that administration of chemotherapeutic
      drugs was the only statistically significant parameter (t = 3.78, p < 0.05), with
      the rate of chemotherapy higher in the cooperative study. CONCLUSIONS: Morbidity,
      mortality, and recurrence rates of hydatidosis uncovered by the cooperative study
      and the literature survey were not statistically significant.

PMID- 10883899
TI  - Surgical treatment of brain metastases from melanoma: a retrospective study of 91
      patients.
AB  - OBJECT: Reports on the surgical treatment of brain metastases from melanoma in a
      large group of patients are sparse. The goal of this paper is to review the
      surgical experience in a series of 91 patients with brain metastases from primary
      melanoma treated at a single institution. METHODS: Seven hundred eighty patients
      underwent resection of brain metastases at Memorial Sloan-Kettering Cancer Center
      between 1974 and 1994. The records of 91 (11.7%) of these patients who had
      melanoma were retrospectively reviewed. The median time from diagnosis of the
      primary melanoma to diagnosis of the brain lesion was 14.1 months. The overall
      median length of survival following craniotomy was 6.7 months. Fifteen patients
      with resected multiple metastases had shorter median survival times than 76
      patients with a single lesion (5.4 months compared with 7.8 months, p = 0.12). In
      eight patients with cerebellar metastases the median length of survival was
      significantly shorter than that found in patients with supratentorial lesions (2
      compared with 7 months, p = 0.03). There was no difference in length of survival
      between 49 patients who underwent postoperative whole-brain radiation therapy
      (WBRT) and 29 patients who did not (9.5 compared with 8.3 months, p = 0.67). The
      incidence of brain metastasis recurrences in WBRT-treated and untreated patients
      was similar (56% and 45.7%, respectively). Only the presence of infratentorial
      metastases (p = 0.0013) and unresected recurrence of brain metastases (p =
      0.0003) had an impact on outcome according to a Cox regression analysis. Five
      patients (5.5%) died within 31 days of surgery. Overall survival rates at 1, 2,
      3, and 5 years were 36.3, 18.7, 13.2, and 6.6%, respectively. CONCLUSIONS:
      Although melanoma metastatic to the brain carries a foreboding prognosis,
      patients who do not display preoperative neurological deficits, harbor a single
      lesion situated supratentorially, and have no lung or visceral metastases may
      derive significant palliative benefit from surgical resection of brain
      metastases.

PMID- 10883900
TI  - Long-term follow-up study of unruptured vertebral artery dissection: clinical
      outcomes and serial angiographic findings.
AB  - OBJECT: Although the spontaneous occurrence of an unruptured vertebral artery
      (VA) dissection has increasingly been recognized as a relatively common cause of
      stroke, and the clinical aspects of this lesion have gradually been determined,
      its natural course remains obscure. The main goal of this study was to clarify
      the management protocol for this condition by examining serial angiographic
      changes in patients with unruptured VA dissections. METHODS: Seventeen patients
      with unruptured VA dissections, including 13 men and four women, were clinically
      and angiographically examined between 1993 and 1998. All patients were observed
      using serial angiography studies. The initial angiography examinations most
      frequently revealed stenotic lesions (appearance of a pearl-and-string sign or
      string sign) in eight (47.1%) of 17 cases. In 15 cases (88.2%), changes in the
      lesions were evident on follow-up angiography studies. Stenotic lesions resulted
      in occlusion in four cases, normalization in three, and subsequent formation of
      an aneurysm in one case, which was treated successfully by proximal occlusion of
      the affected vessel performed using a detachable balloon. Occluded lesions, which
      were initially observed in three patients, recanalized in two patients and
      remained unchanged in one patient. Fusiform dilation alone was demonstrated in
      three patients during the initial angiography session; these lesions became
      normalized or were unchanged on follow-up studies. Saccular aneurysms were
      observed in two patients. In one of these cases, proximal ligation of the parent
      artery was successfully performed because of subsequent aneurysm enlargement. A
      double lumen, which appeared in one patient with an extradural VA dissection,
      became occluded. Magnetic resonance T2-weighted imaging studies revealed
      infarction corresponding to the posterior circulation in seven cases. During long
      term observation in this series, good or excellent recovery was obtained in 14
      (87.5%) of 16 patients, and moderate or severe disability in two (12.5%); one
      patient was lost to follow up after the second angiography study. CONCLUSIONS: A
      follow-up angiography study must be performed during the early stage (within
      approximately 3 weeks after onset of symptoms) to confirm the formation or
      enlargement of an aneurysm, because such conditions may be amenable to surgical
      treatment. Unruptured VA dissection could otherwise be treated and followed
      conservatively. Although the majority of dissected lesions seem likely to
      stabilize within a few months, as evidenced on angiography, in some cases a
      longer observation period is required.

PMID- 10883901
TI  - Brachial plexus dorsal rhizotomy in the treatment of upper-limb spasticity.
AB  - OBJECT: This study was conducted to evaluate the effects of dorsal rhizotomy on
      upper-limb spasticity, functional improvement, coordination, and hand
      sensibility. METHODS: Fifteen spastic upper limbs in 13 patients were selected
      and prospectively studied. Brachial plexus dorsal rhizotomy was performed in
      which two, three, or four dorsal roots were completely sectioned. Patients were
      followed up for at least 12 months after surgery; the mean follow-up period was
      15.6 months and the maximum period was 30 months. A remarkable relief of
      spasticity was observed in all cases. Recurrence was observed in only one patient
      and was caused by insufficient dorsal root section. Functional improvement was
      observed in all cases, and functional improvement in the hand was found to be
      related to the presence of active finger extension in the preoperative period.
      Even when extended dorsal root section was performed, no hand anesthesia, either
      total or partial, was observed. No patient lost movement ability in the
      postoperative period, and no ataxic limbs were observed. CONCLUSIONS: Brachial
      plexus dorsal rhizotomy is very effective as a treatment for upper-limb
      spasticity and results in functional improvement without loss of sensation in the
      hand.

PMID- 10883902
TI  - Venous opthalmodynamometry: a noninvasive method for assessment of intracranial
      pressure.
AB  - OBJECT: The goal of this study was to examine the potential use of
      ophthalmodynamometry in the noninvasive assessment of intracranial pressure
      (ICP). Under normal conditions, pressure within the central retinal vein is equal
      to or greater than ICP, because the central retinal vein basses through the optic
      nerve before it drains into the cavernous sinus. The optic nerve sheath is the
      place where ICP affects retinal venous pressure. Suction ophthalmodynamometry is
      an established method of investigation in ophthalmology to determine the pressure
      of the central retinal artery. Although observations of papilledema and lack of
      venous pulsations are commonly used to provide a vague assessment of ICP,
      ophthalmodynamometry may be used to determine the pressure of the central retinal
      vein. This venous pressure has never been compared with ICP. METHODS: In this
      study the pressure of the central retinal vein was recorded in 22 patients who
      underwent continuous simultaneous registration of ICP for various reasons, mainly
      for suspected hydrocephalus. A comparison of the two pressures was made. The
      results indicated a highly significant linear correlation between central retinal
      vein pressure and ICP. These results are of great practical value because up-to
      date reliable ICP monitoring has only been possible by using invasive means, by
      placing a probe extradurally or subdurally into the brain parenchyma or a
      ventricle. CONCLUSIONS: Ophthalmodynamometry can be relevant for momentary
      assessment and is not suitable for continuous monitoring. However, this technique
      can easily be repeated and may be used whenever increased ICP is suspected in a
      patient suffering from hydrocephalus, brain tumors, or head injury.

PMID- 10883903
TI  - Clinical cerebral microdialysis: a methodological study.
AB  - OBJECT: Clinical microdialysis enables monitoring of the cerebral extracellular
      chemistry of neurosurgical patients. Introduction of the technique into different
      hospitals' neurosurgical units has resulted in variations in the method of
      application. There are several variables to be considered, including length of
      the catheter membrane, type of perfusion fluid, flow rate of perfusion fluid, and
      on-line compared with delayed analysis of samples. The objects of this study were
      as follows: 1) to determine the effects of varying catheter characteristics on
      substance concentration; 2) to determine the relative recovery and true
      extracellular concentration by varying the flow rate and extrapolating to zero
      flow; and 3) to compare substance concentration obtained using a bedside enzyme
      analyzer with that of off-line high-performance liquid chromatography (HPLC).
      METHODS: A specially designed bolt was used to conduct two adjacent microdialysis
      catheters into the frontal cortex of patients with head injury or poor-grade
      subarachnoid hemorrhage who were receiving ventilation. One reference catheter
      (10-mm membrane, perfused with Ringer's solution at 0.3 microl/minute) was
      constant for all studies. The other catheter was varied in terms of membrane
      length (10 mm or 30 mm), perfusion fluid (Ringer's solution or normal saline),
      and flow rate (0.1-1.5 microl/minute). The effect of freezing the samples on
      substance concentration was established by on-line analysis and then repeated
      analysis after storage at -70 degrees C for 3 months. Samples assayed with the
      bedside enzyme analyzer were reassessed using HPLC for the determination of
      glutamate concentrations. CONCLUSIONS: Two adjacent microdialysis catheters that
      were identical in membrane length, perfusion fluid, and flow rate showed
      equivalent results. Variations in perfusion fluid and freezing and thawing of
      samples did not result in differences in substance concentration. Catheter length
      had a significant impact on substance recovery. Variations in flow rate enabled
      the relative recovery to be calculated using a modification of the extrapolation
      to-zero-flow method. The recovery was approximately 70% at 0.3 microl/minute and
      30% at 1 microl/minute (10-mm membrane) for all analytes. Glutamate results
      obtained with the enzyme analyzer showed good correlation with those from HPLC.

PMID- 10883904
TI  - Intraoperative hippocampal electrocorticography to predict the extent of
      hippocampal resection in temporal lobe epilepsy surgery.
AB  - OBJECT: Among the variety of surgical procedures that are performed for the
      treatment of medically refractory mesial temporal lobe epilepsy (TLE), no
      consensus exists as to how much of the hippocampus should be removed. Whether all
      patients require a maximal hippocampal resection has not yet been determined.
      METHODS: At the University of Washington, all TLE operations are performed in a
      tailored fashion, guided by electrocorticography (ECoG). The amount of
      hippocampal resection is determined intraoperatively by the extent of interictal
      epileptiform abnormalities on ECoG recorded from that structure, resulting in a
      hippocampal resection that is individualized for each patient. Using this
      approach, the authors prospectively observed 140 consecutive patients who
      underwent surgery for mesial TLE with pathological diagnoses of either mesial
      temporal sclerosis with neuronal loss (MTS group) or mild gliosis without
      neuronal loss (non-MTS group) to determine whether the extent of hippocampal
      resection correlates with outcome when a tailored approach is used. Additionally,
      the authors analyzed whether the presence of residual interictal epileptiform
      activity on ECoG following mesial temporal resection predicts poorer seizure
      control. With at least 18 months of clinical follow up, 67% of the 140 patients
      were seizure free or had only a single postoperative seizure. There was no
      correlation between the size of the hippocampal resection and seizure control in
      the group as a whole or when stratified by pathological subtype. Using an
      intraoperatively tailored strategy, individuals with a larger hippocampal
      resection (> 2.5 cm) were not more likely to have seizure-free outcomes than
      patients with smaller resections (p = 0.9). Additionally, both MTS and non-MTS
      patients, in whom postoperative ECoG detected residual epileptiform hippocampal
      (but not cortical or parahippocampal) interictal activity following surgical
      resection, had significantly worse seizure outcomes (p = 0.01 in the MTS group; p
      = 0.002 in the non-MTS group). CONCLUSIONS: Intraoperative hippocampal ECoG can
      predict how much hippocampus should be removed to maximize seizure-free outcome,
      allowing for sparing of possibly functionally important hippocampus.

PMID- 10883905
TI  - Influence of cranioplasty on postural blood flow regulation, cerebrovascular
      reserve capacity, and cerebral glucose metabolism.
AB  - OBJECT: The indications for cranioplasty after decompressive craniectomy are
      cosmetic repair and, mainly, restoration of cerebral protection. Although
      neurological improvement after cranioplasty is repeatedly noted, the reasons for
      this remain unclear. Few observations concerning the impact of cerebrospinal
      fluid hydrodynamic and/or atmospheric pressure have been published during the
      last decades. Relevant data concerning the cerebrovascular reserve (CVR) capacity
      and cerebral glucose metabolism before and after cranioplasty have been lacking
      until now. To gain further insight, this study was undertaken to investigate the
      impact of cranioplasty on indices of cerebral blood flow regulation and
      metabolism. METHODS: Thirteen patients in whom extensive craniectomies had been
      performed underwent a meticulous study of blood flow velocities in the middle
      cerebral artery (MCA) and extracranial internal carotid artery (ICA), as assessed
      by transcranial Doppler ultrasonography during postural maneuvers (supine and
      sitting positions) and during stimulation with 1 g of acetazolamide for the
      interpretation of CVR capacity. Twelve patients underwent 18-fluorodeoxyglucose
      positron emission tomography. These measurements were obtained before and 7 days
      after cranioplasty. Cranioplasty improved preoperative differences in MCA blood
      flow velocities when comparing those in the injured with those in the uninjured
      hemisphere. Similarly, cranioplasty resolved decreases in extracranial ICA blood
      flow in the injured hemisphere that were induced by postural changes, which was a
      constant finding prior to this procedure. More strikingly, however, the CVR
      capacity, which was severely impaired in both hemispheres, increased
      significantly after the procedure. Metabolic deficits, which were observed in the
      injured hemisphere, were found to improve after reimplantation of the skull bone
      flap. CONCLUSIONS: Cranioplasty appears to affect postural blood flow regulation,
      CVR capacity, and cerebral glucose metabolism markedly. Thus, early cranioplasty
      is warranted to facilitate rehabilitation in patients after decompressive
      craniectomy.

PMID- 10883906
TI  - Possible origin of suprasellar arachnoid cysts: neuroimaging and neurosurgical
      observations in nine cases.
AB  - OBJECT: In this study the authors identify and investigate two new
      classifications of suprasellar arachnoid cysts. METHODS: The authors used
      computerized tomography cisternography, magnetic resonance (MR) imaging, and
      neuroendoscopy to investigate nine cases of suprasellar arachnoid cysts. A
      communicating cyst with early filling and early clearance of a radioopaque tracer
      was found in seven of nine cases; a communicating cyst with delayed filling and
      delayed clearance of the tracer was observed in one case; and a noncommunicating
      cyst was observed in the other. The MR findings indicated a variation in the
      position of the basilar artery (BA) bifurcation in relation to the ventral
      surface of the midbrain. A distance existed between the BA bifurcation and the
      ventral surface of the midbrain in a communicating cyst with early filling,
      whereas the BA bifurcation was posteriorly displaced in a communicating cyst with
      delayed filling and also in a noncommunicating cyst, leaving little space between
      the bifurcation and the ventral surface of the midbrain. Endoscopic observation
      revealed, in the case of communicating cysts with early filling and early
      clearance of tracer, that the BA bifurcation is located inside the cyst with no
      overlying membrane, whereas in a noncommunicating cyst, the BA and its branches
      can be observed through the transparent membrane of the lesion. CONCLUSIONS: The
      authors postulate two different types of suprasellar arachnoid cysts: a
      noncommunicating intraarachnoid cyst of the diencephalic membrane of Liliequist
      and a communicating cyst that is a cystic dilation of the interpeduncular
      cistern.

PMID- 10883907
TI  - Experimental study of medullary trigeminal evoked potentials: development of a
      new method of intraoperative monitoring of the medulla oblongata.
AB  - OBJECT: The goal of this study was to develop a new method of intraoperative
      monitoring of functions located in the lateral portion of the medulla oblongata.
      Based on the fact that the spinal trigeminal nucleus and tract are located in the
      lateral portion of the medulla oblongata, the authors intended to investigate the
      efficacy of trigeminal evoked potentials (TEPs) in intraoperative monitoring for
      assessing functions of the medulla oblongata. METHODS: Trigeminal evoked
      potentials induced by electrical stimulation of the infraorbital nerve were
      recorded from the dorsolateral portion of the medulla oblongata (M-TEP) and the
      cerebral sensory cortex (C-TEP) in dogs. When the lateral one-sixth portion of
      the medulla was cut, the amplitude of the M-TEP decreased markedly, but the
      amplitude of the C-TEP and the somatosensory evoked potential (SSEP) did not
      decrease. When the lateral one-third portion of the medulla was cut, the
      amplitude of the SSEP decreased, but that of the C-TEP showed no change. When the
      medulla was retracted, the amplitude of the M-TEP was more sensitive than that of
      SSEP. Pathological examinations revealed that retraction force less than 10 g and
      a reduction in the amplitude of the M-TEP less than 50% were safe. CONCLUSIONS:
      These results suggest that M-TEPs obtained from the dorsolateral portion of the
      medulla oblongata by electrical stimulation of the trigeminal nerve are
      clinically applicable as a new means of intraoperative monitoring of the
      functions of the medulla oblongata.

PMID- 10883908
TI  - Detection of chromosomal imbalances in central neurocytomas by using comparative
      genomic hybridization.
AB  - OBJECT: Central neurocytomas are rare neuronal tumors commonly found in the
      intraventricular regions. Little is known about the tumorigenesis of these
      neoplasms. The aim of this study was to provide an overview of genetic imbalances
      in central neurocytomas. METHODS: In this study, comparative genomic
      hybridization was used to identify DNA sequence copy number changes (losses and
      gains) in a series of 10 central neurocytomas. Tumor DNA and normal reference DNA
      were differentially labeled and allowed to cohybridize to normal metaphase
      chromosomes. After hybridization and fluorescent staining of the bound DNA,
      regions of gain or of loss of DNA sequences were detected as changes in the
      tumor/normal fluorescence intensity ratio along the target metaphase chromosomes.
      A gain of DNA sequence was detected in chromosomes 2p, 10q, and 18q. A
      protooncogene, Bcl2, which maps to 18q21, was evaluated by immunohistochemical
      analysis to determine its role in the formation of central neurocytomas.
      CONCLUSIONS: In this study the authors identified recurrent genetic changes on
      chromosomes 2p, 10q, and 18q in central neurocytomas and highlighted chromosomal
      regions for additional mapping and cloning of candidate genes that are important
      in the development of central neurocytomas.

PMID- 10883909
TI  - Temporal changes in sensitivity of rats to cerebral ischemic insult.
AB  - OBJECT: Experimental rat models are often used to study cerebral ischemia, yet
      rats are nocturnal animals that have activity cycles that are the opposite of
      those of humans. In the following study the authors examined the circadian rhythm
      of sensitivity to an ischemic insult in rats by using an intraluminal thread
      technique to produce reversible middle cerebral artery occlusion. METHODS:
      Ischemia (2 hours of blockage followed by 22 hours of reperfusion) was induced in
      rats according to the 24-hour clock at either 100, 400, 700, 1,000, 1,300, 1,600,
      1,900, or 2,200 hours (11-14 rats per time period). The rat brains were removed,
      coronally sectioned, stained with 2,3,5-triphenyltetrazolium chloride and
      analyzed using commercially available software. Analysis of variance and cosinor
      rhythmometry statistical tests were used for analysis of data. The time of day
      when the ischemic infarct was induced had a significant (p = 0.011) influence on
      the volume of the lesion. The volume of total brain infarct produced at 400 hours
      (7.65 +/- 1.31%) was more than three times greater than the volume produced at
      1600 hours (2.1 +/- 0.34%). Cosinor-rhythm analysis indicated a peak occurrence
      of infarct volume at 6:02 (95% confidence interval 5:49-6:16). The size of the
      infarct correlated with core body temperature rhythms, which varied by 1.3 +/-
      0.62 degrees C (mean +/- standard deviation). CONCLUSIONS: Circadian rhythms, as
      well as the reversed natural body rhythms of the rat compared with humans, should
      be considered when extrapolating data to human or other animal studies. Temporal
      rhythms may also provide information concerning the cascading disease processes
      associated with cerebral ischemia.

PMID- 10883910
TI  - Effectiveness of preoperative administration of an N-methyl-D-aspartate
      antagonist to enhance cochlear neuron resistance to intraoperative traumatic
      stress: an experimental study.
AB  - OBJECT: Cochlear neurons are inevitably exposed to traumatic stress during
      surgical removal of an acoustic neuroma; that event is an important cause of
      postoperative cochlear neuronal degeneration, with subsequent loss of spiral
      ganglion cells (SGCs). The object of this study was to investigate whether
      preoperative pharmacological treatment can enhance the resistance of cochlear
      neurons to the traumatic stress of surgery. METHODS: Cochlear neuronal
      degeneration was induced in 17 rats by controlled compression of the
      cerebellopontine angle portion of the cochlear nerve. Dizocilpine maleate (MK
      801; 10 mg/kg), an N-methyl-D-aspartate (NMDA) antagonist, was administered
      intraperitoneally to six of the 17 rats 30 minutes before compression occurred.
      Two weeks after compression, each rat was killed, and the numbers of SGCs in
      histological preparations of temporal bones were counted. CONCLUSIONS: Spiral
      ganglion cells were more numerous in rats administered dizocilpine maleate (p <
      0.03) than in rats that did not receive treatment, indicating that receptor
      mediated glutamate neurotoxicity may participate in the pathogenesis of trauma
      induced cochlear neuron death and that administration of an NMDA antagonist
      before surgery may protect the nerve from injury leading to hearing loss.

PMID- 10883911
TI  - Production of reactive oxygen species after reperfusion in vitro and in vivo:
      protective effect of nitric oxide.
AB  - OBJECT: Thrombolytic treatments for ischemic stroke can restore circulation, but
      reperfusion injury, mediated by oxygen free radicals, can limit their utility.
      The authors hypothesized that, during reperfusion, nitric oxide (NO) provides
      cytoprotection against oxygen free radical species. METHODS: Levels of NO and
      oxygen free radicals were determined in both reoxygenation in vitro and
      reperfusion in vivo models using an NO electrochemical probe and high-performance
      liquid chromatography with the 2,3- and 2,5-dihydroxybenzoic acid trapping
      method, before and after addition of the NO donor diethanolamine nitric oxide
      (DEA/NO). Reoxygenation after anoxia produced a twofold increase in NO release by
      human fetal astrocytes and cerebral endothelial cells (p < 0.005). In both cell
      lines, there was also a two- to threefold increase in oxygen free radical
      production (p < 0.005). In human fetal astrocytes and cerebral endothelial cells
      given a single dose of DEA/NO, free radical production dropped fivefold compared
      with peak ischemic levels (p < 0.001). In a study in which a rat global cerebral
      ischemia model was used, NO production in a vehicle-treated group increased 48 +/
      16% above baseline levels after reperfusion. After intravenous DEA/NO infusion,
      NO reached 1.6 times the concentration of the postischemic peak in vehicle
      treated animals. In vehicle-treated animals during reperfusion, free radical
      production increased 4.5-fold over basal levels (p < 0.01). After intravenous
      DEA/NO infusion, free radical production dropped nearly 10-fold compared with
      peak levels in vehicle-treated animals (p < 0.006). The infarct volume in the
      vehicle-treated animals was 111 +/- 16.9 mm3; after DEA/NO infusion it was 64.8
      +/- 23.4 mm3 (p < 0.01). CONCLUSIONS: The beneficial effect of early restoration
      of cerebral circulation after cerebral ischemia is limited by reperfusion injury.
      These results indicate that NO release and oxygen free radical production
      increase during reperfusion, and suggest a possible early treatment of
      reperfusion injury using NO donors.

PMID- 10883912
TI  - Classification and quantification of the petrosal approach to the petroclival
      region.
AB  - OBJECT: The petrosal approach to the petroclival region has been used by a
      variety of authors in various ways and the terminology has become quite
      confusing. A systematic assessment of the benefits and limitations of each
      approach is also lacking. The authors classify their approach to the middle and
      upper clivus, review the applications for each, and test their hypotheses on a
      cadaver model by using frameless stereotactic guidance. METHODS: The petrosal
      approach to the upper and middle clivus is divided into four increasingly
      morbidity-producing steps: retrolabyrinthine, transcrusal (partial
      labyrinthectomy), transotic, and transcochlear approaches. Four latex-injected
      cadaveric heads (eight sides) underwent dissection in which frameless
      stereotactic guidance was used. An area of exposure 10 cm superficial to a
      central target (working area) was calculated. The area and length of clival
      exposure with each subsequent dissection was also calculated. The
      retrolabyrinthine approach spares hearing and facial function but provides for
      only a small window of upper clival exposure. The view afforded by what we have
      called the transcrusal approach provides for up to four times this exposure. The
      transotic and transcochlear procedures, although producing more morbidity, add
      little in terms of a larger clival window. However, with each step, the surgical
      freedom for manipulation of instruments increases. CONCLUSIONS: The petrosal
      approach to the upper and middle clivus is useful but should be used judiciously,
      because levels of morbidity can be high. The retrolabyrinthine approach has
      limited utility. For tumors without bone invasion, the transcrusal approach
      provides a much more versatile exposure with an excellent chance of hearing and
      facial nerve preservation. The transotic approach provides for greater
      versatility in treating lesions but clival exposure is not greatly enhanced.
      Transcochlear exposure adds little in terms of intradural exposure and should be
      reserved for cases in which access to the petrous carotid artery is necessary.

PMID- 10883913
TI  - Facial nerve repair accomplished by the interposition of a collagen nerve guide.
AB  - OBJECT: Facial nerve paralysis due to a surgical procedure or trauma is a
      frequently observed complication. The authors evaluated facial nerve repair
      achieved by the interposition of a collagen nerve guide. METHODS: Ten cats were
      divided into three groups. Group 1 consisted of six animals in which a 5-mm
      facial nerve segment on one side was resected and replaced by a collagen tube
      that was sutured to bridge both nerve stumps. On the opposite side a 5-mm segment
      of facial nerve was resected, reversed 180 degrees, and sutured to the stumps as
      an autograft nerve. Group 2 consisted of two cats in which the collagen nerve
      guide was interposed on one side and the nerve on the other side was left intact.
      Group 3 consisted of two cats in which a reversed autograft nerve was placed on
      one side and the nerve on the other side was left intact. Histological,
      electrophysiological, and horseradish peroxidase labeling examinations were
      performed starting 3 weeks after surgery. Light and electron microscopic
      examinations of collagen tube-implanted specimens revealed a well-vascularized
      regenerated nerve. The electrophysiological study confirmed the recovery of
      electrical activity in regenerated axons. Horseradish peroxidase labeling also
      confirmed restoration of the whole facial nerve tract. CONCLUSIONS: The collagen
      nerve guide shows great promise as a nerve conduit.

PMID- 10883914
TI  - Acromegaly associated with a granular cell tumor of the neurohypophysis: a
      clinical and histological study. Case report.
AB  - Acromegaly is usually caused by a growth hormone (GH)-secreting pituitary
      adenoma, and hypersecretion of GH-releasing hormone (GHRH) from a hypothalamic or
      neuroendocrine tumor accounts for other cases. The authors report on the unusual
      association of acromegaly with a granular cell tumor of the neurohypophysis. A 42
      year-old woman with a 10-year history of acral enlargement, headache, and
      menstrual abnormalities was referred to our department for a suspected GH
      secreting pituitary adenoma. The patient's basal GH levels were mildly elevated
      at 4.8 microg/L, were not suppressed in response to an oral glucose tolerance
      test, and increased paradoxically after administration of thyrotropin-releasing
      hormone. The patient's insulin-like growth factor-1 (IGF-1) level was elevated at
      462 microg/L, whereas a magnetic resonance image of the sella turcica revealed an
      intra- and suprasellar lesion that was compatible with a diagnosis of pituitary
      adenoma. A transsphenoidal approach to remove the lesion, which was mainly
      suprasellar, was successful during a second operative attempt, resulting in the
      clinical and biochemical regression of the patient's acromegaly. Four months
      postoperatively, the patient's basal GH level was 0.9 microg/L and her IGF-1
      level was 140 microg/L. Histological analysis of the operative specimen
      demonstrated a granular cell tumor of the neurohypophysis, which when stained
      proved negative for pituitary hormones and GHRH. This case represents the first
      reported association between a granular cell tumor of the neurohypophysis and
      acromegaly. Granular cell tumor of the neurohypophysis could be added to the
      restricted list of neoplastic causes of acromegaly secondary to hypersecretion of
      a GH-releasing substance.

PMID- 10883915
TI  - Efficacy of unilateral deep brain stimulation of the thalamic ventralis
      intermedius nucleus in a patient with bipolar disorder associated with
      Klinefelter syndrome and essential tremor. Case report.
AB  - Deep brain stimulation (DBS) of the ventralis intermedius nucleus (Vim) is a safe
      and effective treatment for essential tremor. Bipolar disorder and essential
      tremor had each been reported to occur in association with Klinefelter syndrome
      but the three diseases have been reported to occur together in only one patient.
      The genetic basis and natural history of these disorders are not completely
      understood and may be related rather than coincidental. The authors report on a
      23-year-old man with Klinefelter syndrome (47,XXY) and bipolar disorder who was
      treated successfully with unilateral DBS of the thalamic Vim for essential
      tremor.

PMID- 10883916
TI  - Transcranial-transdural real-time ultrasonography during transsphenoidal
      resection of a large pituitary tumor. Case report.
AB  - Ultrasonography has been used in neurosurgical operative procedures for several
      decades. The authors report the case of a large pituitary tumor that was
      subtotally resected using endoscopy via the transnasal-transsphenoidal approach,
      with the aid of transcranial real-time ultrasound. To our knowledge, this is the
      first reported case in which intraoperative transcranial-transdural real-time
      ultrasound was used to facilitate the resection of a skull base tumor.

PMID- 10883917
TI  - Regression of a presumed meningioma with the antiestrogen agent mepitiostane.
      Case report.
AB  - This 68-year-old woman underwent a distal gastrectomy for gastric cancer in
      August 1994. A presumed meningioma of the falx was found incidentally on a
      staging examination of the gastric cancer, but the meningioma was not treated
      with surgery. Instead, after gastrectomy the patient received tegafur as adjuvant
      chemotherapy until February 1996, when she was readmitted to the hospital because
      of loss of appetite and emaciation but with no recurrence of the gastric cancer.
      A computerized tomography scan obtained during this second admission showed no
      change in the meningioma. To improve her general condition, tegafur was
      discontinued and she was started on a course of the antiestrogen agent
      mepitiostane. Administration of mepitiostane for approximately 2 years resulted
      in a marked regression (73%) of the meningioma. This is the first reported case
      of a presumed meningioma that regressed as a result of use of the antiestrogen
      agent mepitiostane.

PMID- 10883918
TI  - Heparin-induced thrombocytopenia and thrombosis following subarachnoid
      hemorrhage. Case report.
AB  - The authors present a case of heparin-induced thrombocytopenia and thrombosis
      (HITT) that occurred after aneurysmal subarachnoid hemorrhage (SAH), and they
      review the relevant literature. An immune-mediated syndrome, HITT is
      characterized by moderate thrombocytopenia and paradoxical vascular thromboses.
      Although it has been estimated in prospective studies that HITT occurs in between
      1 and 3% of patients receiving heparin, it is underrecognized in the
      neurosurgical literature. In the present case, a 49-year-old woman underwent
      clipping of a right posterior communicating artery aneurysm after suffering a
      Hunt and Hess Grade III SAH. She had an uncomplicated postoperative course with
      good clip positioning and no vasospasm observed on a cerebral angiogram obtained
      on Day 7. On Day 23, the patient developed a right hemiparesis and experienced a
      grand mal seizure. A head computerized tomography scan revealed a hemorrhagic
      infarct in the left middle cerebral artery distribution. Repeated cerebral
      angiograms did not show vasospasm. She was thrombocytopenic (platelet count as
      low as 46 x 10(9)/L on Day 28 compared with 213 x 10(9)/L on Day 1) and had been
      receiving heparin flushes to maintain intravenous catheter patency. An assay for
      HITT-associated antibodies was positive. The heparin flushes were discontinued
      and the platelet count recovered (121 x 10(9)/L). She improved neurologically,
      but was left with a significant right hemiparesis at discharge. This patient had
      assay-proven heparin-induced thrombocytopenia despite minimal exposure to
      heparin. Because there was no evidence of vasospasm or other factors to account
      for her delayed hemorrhagic infarction, an HITT-related disorder seemed most
      likely. Despite a large body of literature describing HITT in nonneurosurgical
      patients, only three previous neurosurgical cases have been published. This case
      report may serve to heighten awareness of this disorder.

PMID- 10883919
TI  - Long-term deep brain stimulation in a patient with essential tremor: clinical
      response and postmortem correlation with stimulator termination sites in ventral
      thalamus. Case report.
AB  - Essential tremor can be suppressed with chronic, bilateral deep brain stimulation
      (DBS) of the ventralis intermedius nucleus (Vim), the cerebellar receiving area
      of the motor thalamus. The goal in this study was to correlate the location of
      the electrodes with the clinical efficacy of DBS in a patient with essential
      tremor. The authors report on a woman with essential tremor in whom chronic
      bilateral DBS directed to the ventral thalamus produced adequate tremor
      suppression until her death from unrelated causes 16 months after placement of
      the electrodes. Neuropathological postmortem studies of the brain in this patient
      demonstrated that both stimulators terminated in the Vim region of the thalamus,
      and that chronic DBS elicited minor reactive changes confined to the immediate
      vicinity of the electrode tracks. Although the authors could not identify
      neuropathological abnormalities specific to essential tremor, they believe that
      suppression of essential tremor by chronic DBS correlates with bilateral
      termination of the stimulators in the Vim region of the thalamus.

PMID- 10883920
TI  - Innovative approach in the diagnosis of medulloblastoma in which the 123I
      metaiodobenzylguanidine single-photon emission computerized tomography technique
      is used. Case illustration.

PMID- 10883921
TI  - Tethered brain. Case illustration.

PMID- 10883922
TI  - Contralateral subdural hematoma resulting from intraoperative aneurysm rupture.
      Case illustration.

PMID- 10883923
TI  - Henry Schwartz's address to the Society of Neurological Surgeons, May 1998.

PMID- 10883924
TI  - Endoscopic approach to tectal tumors.

PMID- 10883925
TI  - Optimal treatment for meningiomas.

PMID- 10883926
TI  - Expanding lacunae causing triventricular hydrocephalus.

PMID- 10883927
TI  - Acquired immunodeficiency syndrome and central nervous system tumors.

PMID- 10883928
TI  - Radiation therapy for chordomas.

PMID- 10883929
TI  - Cerebral perfusion pressure and clinical outcome.

PMID- 10883930
TI  - Meningioma cleavage.

PMID- 10883931
TI  - Cognition after subarachnoid hemorrhage.

PMID- 10883932
TI  - Cerebral perfusion pressure and contusion volume.

PMID- 10883933
TI  - Meningioma model.

PMID- 10883934
TI  - Neural transplantation.

PMID- 10883935
TI  - Women in NIH-funded research studies: there's good news, and there's bad news.

PMID- 10883936
TI  - Society seeks level playing field for medical research: clinical trials campaign
      encourages women to contribute to future health, close knowledge gap.

PMID- 10883937
TI  - Using health communications for primary prevention of skin cancer: CDC's Choose
      Your Cover campaign.

PMID- 10883938
TI  - Toward optimal health: the experts discuss chronic fatigue syndrome: interview by
      Jodi Godfrey Meisler.

PMID- 10883939
TI  - Cancer in women: prevention and early detection.
AB  - Cancer is the second leading cause of death for women in the United States. In
      1998, there were approximately 600,000 new cases of cancer and 270,000 cancer
      deaths in U.S. women. Many of these cancer deaths are preventable. In 1987, lung
      cancer replaced breast cancer as the leading cause of cancer deaths in U.S.
      females. Cancer of the lung and bronchus was responsible for 25% of cancer deaths
      in U.S. women last year, killing approximately 67,000 women. It has been
      estimated that almost 90% of lung cancer deaths are associated with cigarette
      smoking and, therefore, are preventable. Some approaches to smoking cessation are
      reviewed. Breast cancer was responsible for 30% of cancers (178,700 women) and
      16% of cancer deaths (43,500 women). Strategies for early detection and,
      possibly, for prevention are reviewed. The third most common cancer and the third
      most common cause of cancer deaths in U.S. women is colorectal cancer. Strategies
      for prevention and early detection are addressed. Cancer of the reproductive
      system affects approximately 80,000 U.S. women each year and results in
      approximately 27,000 deaths. Current screening capabilities, as well as some of
      the limitations of our current screening technologies, are addressed. The
      healthcare team, working in concert with our patients, government, and the health
      insurance industry, should be able to substantially reduce both the incidence of
      and mortality from cancer in women.

PMID- 10883940
TI  - Endocrinology teaching rounds: primary amenorrhea in a 17-year-old woman.
AB  - This endocrinology teaching rounds documents the evaluation of a 17.7-year-old
      woman with primary amenorrhea. The normal timing of developmental milestones for
      young women from adrenarche and pubarche through pubertal maturation and growth
      is reviewed, as are etiologies for amenorrhea. The differential diagnosis of the
      problem is developed from the patient's initial visit to diagnosis and treatment.
      The highlights of the management of this young woman after a diagnosis of
      craniopharyngioma are also discussed. This clinical case emphasizes the
      importance of understanding normal developmental landmarks and of detecting
      aberrant physiology-associated amenorrhea even when screening laboratory tests
      appear normal so that defects in normal development can be addressed earlier in
      life.

PMID- 10883941
TI  - Women subjects in NIH-funded clinical research literature: lack of progress in
      both representation and analysis by sex.
AB  - The National Institutes of Health (NIH) issued guidelines in 1990 requiring the
      inclusion of women and minorities in all NIH-sponsored clinical research and
      revised these guidelines in 1994 to require analysis of clinical trial outcomes
      by sex of the subjects. To ascertain whether these guidelines are yet reflected
      in the scientific literature, we performed a survey of research articles
      published in major medical journals. All original research articles in the New
      England Journal of Medicine, the Journal of the American Medical Association, the
      Journal of the National Cancer Institute, and Circulation from the years 1993,
      1995, 1997, and 1998 were examined. Articles were assessed for use of human
      subjects, source of funding, type of study (clinical trial or not), sex
      relatedness of the disease or condition, inclusion of women as study subjects,
      and analysis of outcomes by sex of the subjects. Among NIH-funded, non-sex
      specific studies, approximately one fifth of the studies published each year
      failed to include women as research subjects. This number did not improve
      significantly over the 5-year period analyzed. Only one quarter to one third of
      the studies that included women analyzed data by sex of the subjects, with no
      significant change over the time period studied. Although most clinical trials
      included women as study subjects, in only a small percentage of the trials were
      results analyzed by sex of the subjects, with no significant improvement over
      time. These data clearly show the need for increased awareness and monitoring of
      recruitment and retention of women in clinical research and for analysis of data
      by sex of the subjects to be carried out consistently.

PMID- 10883942
TI  - Vasomotor symptoms are not associated with reduced bone mass in postmenopausal
      women: the Rancho Bernardo Study.
AB  - The association of menopause-related vasomotor symptoms with later bone mineral
      density (BMD) at axial and appendicular sites was examined in community-dwelling
      older women. Subjects were 894 postmenopausal women from the Rancho Bernardo
      Study who had BMD measured in 1988-1991 and responded to a 1989 mailed survey
      that included questions about menopause symptoms. Mean age was 73 years (SE +/-
      9.5, range 47-97), and mean age at menopause was 47 years (SD +/- 6.8, range 21
      62). Vasomotor symptoms were recalled by two thirds (68%) and night sweats by 36%
      of all women, with no significant differences in symptom frequency by age or type
      of menopause. Postmenopausal estrogen (PME) had been used by 644 women (72%) for
      an average duration of 12.3 (+/-11) years. Among women who reported current
      estrogen use with a duration >3 years, those who experienced vasomotor symptoms
      had significantly higher BMD at the lumbar spine (p = 0.01), femoral neck (p =
      0.05) and midshaft radius (p = 0.05) compared with women who did not experience
      symptoms. Vasomotor symptoms were not associated with BMD among past or never PME
      users or among women who reported current PME use for 3 or fewer years. Analyses
      stratified by age, type of menopause, or when PME use began showed similar
      results. Women who reported night sweats also had no difference in BMD compared
      with women without night sweats. In conclusion, vasomotor symptoms are not a
      marker for low BMD years after menopause in women with access to healthcare.
      Vasomotor symptoms significantly increased the likelihood of continued use of
      PME, which was in turn associated with higher BMD levels.

PMID- 10883943
TI  - Reversal of heart failure remodeling in women.
AB  - Epidemiological studies suggest that women with heart failure differ from men
      with heart failure in that their survival is better. Therapeutic trials have not
      clearly demonstrated a survival benefit for women. This study was to determine
      the tolerance for high doses of angiotensin-converting enzyme (ACE) inhibitor
      nitrates in women versus men and to compare their symptomatic response, exercise
      tolerance, and ventricular functional improvement over 1 year. Eighty-eight
      sequential patients with heart failure, 54 men and 34 women with left ventricular
      ejection fraction < or = 35%, were prospectively followed for 1 year. For all
      patients, ACE inhibitor-nitrate therapy was intensified. Each patient had three 6
      monthly echocardiograms at baseline, at 6 months, and at 1 year, and metabolic
      stress testing. Patients were 57.3 +/- 12.3 years old, with New York Heart
      Association (NYHA) class severity 2.6 +/- 1.0. Lisinopril dosages were raised
      from 14 +/- 14 mg/day to 57 +/- 26 mg/day, isosorbide mononitrate from 15 +/- 27
      mg/day to 126 +/- 72 mg/day, and carvedilol (n = 34) to 17 +/- 16 mg/day. Women
      and men were epidemiologically comparable, with similar baseline
      echocardiographic parameters (left ventricular ejection fraction 19% +/- 7%
      versus 17% +/- 6%, respectively). Both tolerated up-titration in medical therapy.
      Final 12-month ejection fractions were equivalent for women and men at 34% +/-
      17% and 34% +/- 13%, respectively, with similar improvements in left ventricular
      diameters. At 1 year, women had higher resting heart rates and remained more
      symptomatic with lower exercise capacity. However, the relative changes in NYHA
      status and aerobic capacity were similar for women and men. Thus, both women and
      men tolerated uptitrated ACE inhibitor-nitrate medical therapy, with comparable
      reversal of heart failure remodeling. Although women continued to be more
      symptomatic than men, relative improvements in symptomatic status, in exercise
      capacity, and in hospitalization rate were equivalent.

PMID- 10883944
TI  - Tubal ligation, menstrual changes, and menopausal symptoms.
AB  - One of the problematic effects of tubal sterilization is menstrual changes or
      disorders, although the results of studies in this area have been inconsistent
      and inconclusive. Recently, there has been growing evidence that tubal
      sterilization protects against ovarian cancer, possibly through physiological
      transformations that result in ovarian dysfunction and decline. This report
      explores the possibility that the biological mechanism of ovarian dysfunction and
      decline may affect the menstrual and menopausal changes that result from hormonal
      imbalances. Using data from a homogeneous population of college alumnae assessed
      for health status, athletic history, and lifestyle characteristics, we focused on
      a premenopausal subgroup of women in the age range of 40-44 years and with at
      least one pregnancy. Multivariate analyses were performed to compare sterilized
      women (n = 56/516, 11%) in this subgroup with nonsterilized women (89%). The two
      groups were alike in mean age, mean parity, body mass index, smoking history,
      physical activity levels, and athletic status. Factors that significantly
      distinguished sterilized women from nonsterilized women were perimenopausal
      symptoms, such as flushing, sweating, breast pain, vaginal dryness, and pain
      associated with menstrual cycles.

PMID- 10883945
TI  - The information problem in women's health: a piece of the solution.
AB  - Researchers and practitioners in the women's health field frequently express
      difficulty in locating information about sex and gender differences in medicine.
      This study hypothesized that a major reason for this is that when sex and gender
      differences are reported in the literature, they are not indexed in a way that
      facilitates locating the information. Search strategies were devised for the
      MEDLINE database to create three bibliographies related to women in each of six
      clinical areas. At one end of the spectrum, the strategy maximized precision (a
      high number of articles found were relevant). At the other end, recall was
      maximized (a high number of the known relevant articles were found). One
      intermediate strategy was formulated in an attempt to find the best combination.
      Precision and recall were measured for each strategy by performing the searches
      (18 total) and then randomly selecting 10 retrieved references. First, the
      abstracts were judged for relevance. Whenever it was not clear from the abstract
      that the article was relevant, women in the field of women's health evaluated the
      original article. The criterion for relevance was provision of clinically useful
      information about the health of women. The results show that it is possible to
      devise an efficient MEDLINE strategy to retrieve on average 64% of articles
      reporting sex or gender differences. This is consistent with the results of other
      studies of retrieval in MEDLINE. Strategies for effective searching are
      recommended.

PMID- 10883946
TI  - Early diagnosis of ectopic pregnancy: can we do it accurately using a biochemical
      profile?
AB  - We wanted to evaluate the utility of seven biochemical markers in the early
      diagnosis of ectopic pregnancy. Women with pain and bleeding suspicious for
      ectopic pregnancy were evaluated prospectively. Each woman had a transvaginal
      sonogram and serum determination of beta-human chorionic gonadotropin (beta-hCG),
      progesterone, estradiol (E2), creatine phosphokinase (CPK), CA-125, 17
      hydroxyprogesterone, and androstenedione. The women were grouped in two ways, and
      there was considerable overlap between the two groups. One grouping included
      those with <45 days of amenorrhea, and the other included those whose beta-hCG
      was <2500 mIU/ml. Each marker was analyzed by univariate and multivariate
      logistic regression to see which could best distinguish ectopic pregnancies from
      nonectopic pregnancies. In the group of women with <45 days of amenorrhea,
      ectopic pregnancies were distinguished by a low progesterone and a high CPK. None
      of the other biochemical markers were significantly associated with ectopic
      pregnancy in the multivariate logistic regression analysis. A receiver operating
      characteristic (ROC) curve was constructed for the CPK/progesterone ratio. As an
      example of different cut points, a CPK/progesterone ratio >15 was 87% sensitive
      and 83% specific in the diagnosis of ectopic pregnancy. In the group of women
      with beta-hCG <2500 mIU/ml, the only biochemical marker found to be significantly
      associated with ectopic pregnancy was CPK. An ROC curve was constructed for CPK
      in this group. As an example of different cut points, a CPK >70 had a 78%
      sensitivity and 81% specificity in the diagnosis of ectopic pregnancy. We
      conclude that the CPK/progesterone ratio is helpful in those women with <45 days
      of amenorrhea, and serum CPK levels are helpful in women whose beta-hCG is <2500
      mIU/ml. Although serum levels of CPK and the ratio of CPK/progesterone are the
      most helpful in making the diagnosis of early ectopic pregnancy, they are not
      good enough to be used alone in clinical practice.

PMID- 10883947
TI  - Striking variation in coronary heart disease mortality in the United States among
      black and white women aged 45-54 by state.
AB  - Coronary heart disease (CHD) is the leading cause of death for women in the
      United States. There has been a substantial decrease in CHD mortality in the past
      few decades in the United States for both women and men. The change in lifestyle
      after World War II may affect the incidence of and mortality from CHD in a more
      recent birth cohort, such as the 45-54-year-old age group. CHD mortality among
      women aged 45-54 by state and race in the United States and other countries in
      1994 was evaluated. Correlation of the CHD mortality with state-specific and race
      specific educational attainment (% of not a high school graduate) and state
      specific prevalence of smoking was examined. There was a 2.5-fold difference in
      CHD mortality (ICD 410-414, 429.2) between black and white women aged 45-54:
      78/100,000 for black versus 31/100,000 for white women; a 3-fold difference in
      CHD mortality among white women by state: 16/100,000 in Colorado versus
      53/100,000 in Louisiana; and a 3-fold difference in CHD mortality among black
      women by state: 45/100,000 in New Jersey versus 124/100,000 in Arkansas. CHD
      mortality was correlated with educational attainment among white women (r = 0.62,
      p = 0.001) and with prevalence of smoking (r = 0.39, p = 0.021). There is a large
      variation in CHD mortality among women aged 45-54 in the United States by race
      and state. These differences may reflect variations in coronary risk factors.
      More detailed evaluation of determinants of CHD mortality by area is needed, as
      are public health programs that can reduce the marked disparity in CHD mortality
      in the United States.

PMID- 10883948
TI  - The effects of tamoxifen on the vaginal epithelium in postmenopausal women.
AB  - Although increased vaginal discharge occurs with treatment, clinicians often
      presume the effects of tamoxifen on the vaginal epithelium are antiestrogenic. We
      studied 16 postmenopausal women before they began tamoxifen treatment, at 6
      months, and then at annual intervals for up to 6 years. Vaginal scrapings for
      cytology smears and maturation values (MV) for these were performed. MV scores
      increased by a mean of 32% and these were predictably related to baseline values,
      with greater increases seen when there were lower scores before treatment. Only
      one woman with an MV of 0 before treatment had no significant changes with 3
      years' treatment. The effects of tamoxifen on the vaginal epithelium are
      influenced by the baseline hormonal milieu and are maturational in the majority
      of postmenopausal women.

PMID- 10883949
TI  - Vulvodynia: a dermatologist's perspective with emphasis on an irritant contact
      dermatitis component.
AB  - Vulvodynia (vulvar burning and itching) is a symptom complex with a number of
      potential triggering/exacerbating factors. We reviewed the management and
      outcomes of 60 patients seen in a referral dermatology clinic for vulvodynia. The
      composite patient profile is that of a 44-year-old white woman with a 2-year
      history of vulvar burning who has tried multiple topical therapies.
      Dermatological factors in these patients included candidiasis (37%), atopy (27%),
      dermatographism (27%), and irritant contact dermatitis (83%). Identification of
      these factors and directed management led to symptomatic improvement in 72% of
      patients within 4 months. No patients were treated with amitriptyline. A
      dermatological approach to discern the contributing factors for individual
      patients with vulvodynia can be helpful in directing therapeutic management.

PMID- 10883950
TI  - Fibromyalgia.

PMID- 10883951
TI  - Women's Health LiteratureWatch.

PMID- 10883952
TI  - Aortic aneurysm size and graft behavior after endovascular stent-grafting:
      clinical experiences and observations over 3 years.
AB  - PURPOSE: To assess the long-term safety and efficacy of aortic endografts in
      terms of clinical outcome, continuing aneurysm exclusion, and changes of aneurysm
      size and graft configuration. METHODS: Between August 1994 and July 1997, 190
      patients (176 men; mean age 68.7 years, range 40-87) with aortic and aortoiliac
      aneurysms were treated with endovascular stent-grafts (Stentor, Vanguard, and
      EGS) in a tertiary care municipal hospital setting. Follow-up involved clinic
      visits every 3 to 6 months with contrast-enhanced computed tomography (CT), color
      duplex, and plain abdominal radiographs at regular intervals; angiography was
      used selectively. All data were collected prospectively and entered into a
      computerized database. RESULTS: Implantation was possible in 188 (98.9%)
      patients. Early conversion to open surgical repair was required in 14 (7.4%)
      patients. Primary endoleaks were detected in 32 (16.8%) patients. Perioperative
      mortality was 0.53% (1/190). During follow-up, 17 (8.9%) additional patients were
      converted to open repair over a mean 20.9 months. Thirty-seven secondary
      procedures to treat endoleaks and pelvic outflow occlusions were performed in 30
      (15.8%) patients. Changes in stent configuration suggestive of endograft
      disintegration were observed in 31 (29.8%) of 104 abdominal radiographs.
      Intraluminal layering of thrombus was seen on contrast-enhanced CT images in 20
      patients. A significant trend (chi(2)4 = 12.34, p < 0.025) toward aneurysm
      enlargement was seen in patients with persistent endoleaks at a mean 18-month
      follow-up. CONCLUSIONS: Although endoleaks after aortic stent-graft placement
      tend to cause ongoing aneurysm growth, we have also observed aneurysm shrinkage
      despite ongoing endoleak. The presence or absence of an endoleak in itself may be
      a poor predictor of successful stent-graft therapy. Lifelong surveillance is
      needed to assure successful aneurysm exclusion and stability or shrinkage of the
      aneurysm sac. Technical improvements in stent materials and design are necessary
      to guarantee long-term stability and safety of the device.

PMID- 10883953
TI  - Can preoperative spiral CT scans alone determine the feasibility of endovascular
      AAA repair? A comparison to angiographic measurements.
AB  - PURPOSE: To determine whether computed tomography (CT) alone can be used for
      excluding patients from endovascular repair for abdominal aortic aneurysms (AAA).
      METHODS: Among 71 patients evaluated for endovascular AAA repair using spiral CT
      imaging and angiography, 31 were selected who had both studies performed within 6
      months of each other using a graduated measuring catheter or guidewire.
      Measurements of aneurysm neck diameter, neck length, and infrarenal aortic length
      were made from the CT and angiographic images using handheld calipers with
      calibration markers as guides. Infrarenal aortic length and neck length were
      determined from CT images by multiplying the width of the cuts by the number of
      slices between the lowest renal artery and the aortic bifurcation or the top of
      the aneurysm, respectively. RESULTS: CT neck diameter measurements differed
      significantly from the angiographic dimensions (6.3 +/- 5.1-mm mean difference, p
      < 0.001). In the majority of patients (25, 81%), CT neck diameters were larger
      (mean 7.3 +/- 3.8 mm). The mean difference in neck length measurements was 0.5 +/
      15.9 mm (p = NS). Twenty-two (71%) patients had aortic length measurements that
      were longer on the angiogram (mean 15.4 +/- 17.2 mm, p = NS). Five patients who
      would have been excluded as candidates based on overestimated CT neck diameter
      measurements subsequently underwent successful endovascular aneurysm repair.
      CONCLUSIONS: Considerable discrepancies exist between preoperative neck diameter
      and infrarenal aortic length measurements obtained from CT scans and angiograms
      used to evaluate candidates for endovascular aortic aneurysm repair. CT alone may
      not be adequate for predicting the feasibility of endovascular AAA repair.

PMID- 10883954
TI  - Aortic stent-grafting with transrenal fixation: use of newly designed spiral Z
      stent endograft.
AB  - PURPOSE: To evaluate the feasibility and efficacy of a newly designed stent-graft
      placed across the renal arteries for exclusion of abdominal aortic aneurysms
      (AAAs) with short or tortuous proximal necks. METHODS: Among a group of AAA
      patients treated with endovascular grafting, 5 had tortuous proximal necks and 13
      had necks <20 mm (mean 13 mm). In these 18 cases, a 2- to 3-cm uncovered segment
      of the stent-graft was placed transrenally using a catheter inserted into the
      renal artery as a guide for graft margin positioning. A newly designed stent
      graft was constructed from a custom-made spiral Z-stent covered with a thin
      walled Dacron material; the endografts were deployed through 16-F (aortoaortic
      model) or 18-F sheaths (bifurcated devices). Renal function was assessed by
      preoperative and postoperative measurement of urea nitrogen and creatinine.
      Aneurysm exclusion and renal artery patency were evaluated during follow-up using
      spiral computed tomography and angiography. RESULTS: The stent-grafts were
      correctly placed at the intended site in all 18 patients. Renal function was not
      affected except transiently in 1 patient who developed bilateral renal artery
      stenoses 24 hours after the procedure; Palmaz stents were deployed in each renal
      artery to reestablish satisfactory blood flow. Of the 33 renal arteries crossed
      by the bare stent-graft segment, all were patent over a mean 14-month follow-up
      (range 7-24), including the patient with Palmaz stents implanted for
      postprocedural renal stenosis. Complete aneurysm exclusion was maintained in 15
      (83%) of 18 patients; proximal leaks persisted in 3 patients, including 2 with
      severely angled proximal necks. CONCLUSIONS: Transrenal placement of the
      uncovered leading edge of custom-made spiral Z-stent-based endografts appears
      feasible and clinically effective in the treatment of AAAs with short or tortuous
      proximal necks.

PMID- 10883955
TI  - Repair of mycotic paravisceral aneurysm with a fenestrated stent-graft.
AB  - PURPOSE: To report the successful endovascular repair of a mycotic paravisceral
      aneurysm using a fenestrated stent-graft. METHODS AND RESULTS: A 55-year-old
      white female with a history of rheumatoid arthritis presented with an 8-cm
      paravisceral aneurysm secondary to pneumonia complicated by empyema.
      Intravascular ultrasound identified a defect in the aortic wall at the level of
      the celiac axis. Repair was accomplished with a fenestrated stent-graft that
      excluded the aneurysm and maintained flow to the celiac axis and superior
      mesenteric artery. Recovery was uneventful and the patient was discharged in 2
      days. Six-month follow-up computed tomographic scanning confirmed aneurysm
      exclusion and flow to the celiac and superior mesenteric arteries. There was no
      evidence of graft infection. The patient died from a clinically diagnosed
      myocardial infarction 10 months after the stent-graft repair. CONCLUSIONS:
      Fenestrated stent-graft repair may evolve into a useful technique for the
      treatment of mycotic paravisceral aneurysms.

PMID- 10883957
TI  - A narrow-waisted aortic aneurysm need not hinder endovascular graft repair.

PMID- 10883956
TI  - A narrow-waisted abdominal aortic aneurysm complicating endovascular repair.
AB  - PURPOSE: To present a case in which a narrow waist in an abdominal aortic
      aneurysm (AAA) complicated endovascular repair using a modular bifurcated stent
      graft. METHODS AND RESULTS: A 68-year-old man underwent endovascular repair of a
      5.9-cm asymptomatic AAA with a self-expanding modular bifurcated stent-graft.
      After insertion and deployment of the stent-graft, the intraoperative completion
      angiogram disclosed unexpected incomplete deployment of the contralateral iliac
      limb due to a narrow waist in the aortic aneurysm. Subsequent angioplasty did not
      increase iliac stent-graft diameter. At follow-up, a tapered course of the
      contralateral iliac leg persisted, without hemodynamic significance. CONCLUSIONS:
      A narrow waist in an AAA may be considered an additional important anatomical
      characteristic in assessing suitability for endovascular repair.

PMID- 10883958
TI  - Vascular response in the femoropopliteal segment after implantation of an ePTFE
      balloon-expandable endovascular graft: an intravascular ultrasound study.
AB  - PURPOSE: To use intravascular ultrasound (IVUS) to document changes in vascular
      dimensions after placement of a balloon-expandable endograft. METHODS: Thirteen
      patients (9 men; mean age 62 years, range 47-75) treated with an investigational
      polytetrafluoroethylene endograft for obstructive disease of the femoropopliteal
      segment were studied with IVUS immediately after endograft implantation and at
      follow-up. Corresponding IVUS cross sections were analyzed for changes in lumen,
      vessel, and plaque areas seen inside the endograft, in the anastomotic segment,
      and in the remote arterial segment. RESULTS: A mean 6-month (range 1.5-9) follow
      up was completed in 12 patients. Matched IVUS cross sections derived from within
      the endograft (n = 12) and at the endograft edges (n = 23) showed no change in
      lumen area (LA) in 17, reduction in 11, and dilatation in 7. Median changes
      within the endograft (+3%) were not significant (p = 0.28) and no neointima was
      found. Cross sections obtained at the anastomotic segment revealed a significant
      increase in LA (85%, p < 0.001), which was associated with a significant increase
      in both vessel area (VA) (42%, p < 0.001) and plaque area (PLA) (15%, p = 0.003)
      area. In the remote arterial segment, the change in LA was minimal (6%, p =
      0.07), as were changes in the VA (9%, p = 0.04) and PLA (10%, p = 0.07).
      CONCLUSIONS: Following endograft placement, luminal changes within the endograft,
      at the endograft edges, and at the remote arterial segments were minimal. Intimal
      hyperplasia was not observed in the endograft. The distinct LA increase at the
      anastomotic segments was determined by the extent of VA and PLA change.

PMID- 10883959
TI  - Treatment of catheter-induced iliac artery injuries with self-expanding
      endografts.
AB  - PURPOSE: To evaluate the efficacy of fabric-covered endoprostheses for
      percutaneous repair of traumatic iliac artery lesions. METHODS: Among 47 patients
      treated for catheter-induced iliac artery injuries, 20 (42%) patients (13 men;
      mean age 58 +/- 10 years, range 41-76) presented with acute (n = 7) or subacute
      (n = 13) lesions considered inappropriate for bare stent implantation (17
      dissecting aneurysms, 2 perforations, and 1 traumatic arteriovenous fistula). The
      self-expanding Cragg EndoPro System I or Passager devices were deployed
      percutaneously to exclude the defects. RESULTS: Immediate exclusion of the lesion
      was achieved in all 20 cases; there were no major procedural complications.
      However, within 24 hours after implantation, fever (n = 11, 55%) and elevations
      in white blood cell count (n = 10, 50%) and C-reactive protein (n = 13, 65%) were
      seen in the majority of patients, which prolonged hospitalization in this group
      (8.4 versus 4.2 days). During a median 21-month follow-up (range 5-31), 2
      angiographically documented restenoses at the outlet of the endografts were
      treated successfully with balloon angioplasty, achieving primary and secondary
      patency rates of 87% and 100%, respectively. CONCLUSIONS: Early model stent
      grafts provided a safe and effective endovascular treatment for iliac
      perforations and large arterial dissections, showing a high mid-term patency
      rate. However, postimplantation syndrome appears to occur frequently with this
      type of Dacron-covered nitinol device.

PMID- 10883961
TI  - A porcine model of carotid artery thrombosis for thrombolytic therapy and
      angioplasty: application of PTFE graft-induced stenosis.
AB  - PURPOSE: To develop a porcine carotid artery thrombosis model for the evaluation
      of thrombolytic therapy and adjunctive angioplasty procedures. METHODS: Bilateral
      carotid thrombosis was induced in 16 pigs using endothelial crush injury followed
      by external polytetrafluoroethylene (PTFE, 5 x 2 cm2) wrap placement to create
      segmental carotid stenosis. Light microscopy was used to examine thrombus
      composition. Selective carotid catheterization was performed via a femoral
      approach. Two hours following carotid artery occlusion, a urokinase (250,000 IU)
      and heparin (1000 U) solution was pulse-sprayed in 1 carotid artery while the
      contralateral vessel received the control saline vehicle. The efficacy of
      thrombolytic therapy was assessed using carotid arteriography and intravascular
      ultrasound. The feasibility and technical efficacy of balloon angioplasty within
      the carotid stenosis model were also evaluated. RESULTS: Carotid artery occlusion
      occurred in 30 +/- 6 minutes following endothelial injury plus PTFE wrap
      placement. Histological examination of carotid arteries showed endothelial
      irregularity with fibrin-rich and platelet-rich thrombus. Urokinase was effective
      in recanalizing all occluded arteries (100%), while the control saline vehicle
      showed no effective thrombolysis (p < 0.001). Angioplasty was successful in
      restoring normal diameter in all arteries (100%). CONCLUSIONS: This carotid
      artery thrombosis model, which incorporates intimal injury with segmental
      stenosis, is simple to create and reproducible. It provides not only a model for
      the evaluation of thrombolytic therapy but also a practical training tool for
      adjunctive endovascular interventions.

PMID- 10883960
TI  - Endovascular treatment of atherosclerotic lower limb lesions using a PTFE
      collared stent-graft.
AB  - PURPOSE: To assess the feasibility of a polytetrafluoroethylene-collared (PTFE)
      endoluminal graft in the treatment of lower limb atherosclerosis. METHODS: We
      designed an endograft using a 3-mm-diameter balloon-expandable PTFE graft with
      terminal Palmaz stents placed on the outside of the graft, folding the PTFE back
      over the stents to form a collar at each end. Under protocol, this device was
      implanted in 8 symptomatic patients with lower limb ischemia. The lesions,
      ranging from 4 to 20 cm long, were located in the superficial femoral artery (n =
      5), femoropopliteal segment (n = 1), and common (n = 1) and external (n = 1)
      iliac arteries. The device required a 14-F introducer system. RESULTS: Graft
      lengths varied from 4 to 35 cm. Implantation was successful in all cases, but
      procedural complications occurred in 4 patients (2 access site hematomas, 1
      leading to endograft occlusion; 1 arterial injury, and 1 distal thromboembolism).
      At a mean 14-month follow-up, 5 endografts were patent (2 after reintervention
      for restenosis or thrombosis). The common iliac endograft and 2 superficial
      femoral artery devices occluded after 3, 2, and 12 months, respectively.
      CONCLUSIONS: Although this endoluminal graft system is technically feasible and
      showed encouraging intermediate-term patency in a small pilot study, the early
      and late complications identified several shortcomings of this design, which
      needs refinement.

PMID- 10883962
TI  - Stent-graft treatment for bleeding from a presumed aortoenteric fistula.
AB  - PURPOSE: To describe a technique for the endovascular treatment of aortoenteric
      fistula. METHODS AND RESULTS: A 67-year-old man who had undergone aortobi-iliac
      grafting for aneurysmal disease 8 years previously presented with life
      threatening upper gastrointestinal hemorrhage. Endoscopy after resuscitation did
      not identify the source of the bleeding. Computed tomographic (CT) scanning and
      angiography revealed pseudoaneurysm formation at the upper anastomosis 1 cm below
      the renal arteries. Measurements were taken for endovascular repair.
      Uncomplicated emergency aortic endografting for exclusion of the pseudoaneurysm
      was performed using a 28-mm x 3.75-cm AneuRx device. Gastrointestinal hemorrhage
      ceased. CT scanning at 6 months confirmed the absence of a pseudoaneurysm, and
      the patient remains symptom free at 18 months. CONCLUSIONS: Endovascular
      treatment of aortoenteric fistula may represent a technique for treating
      gastrointestinal hemorrhage and for lessening the morbidity and mortality of open
      repair.

PMID- 10883963
TI  - Endovascular repair of a presumed aortoenteric fistula: late failure due to
      recurrent infection.
AB  - PURPOSE: To describe a case of presumed aortoduodenal fistula that was treated by
      endovascular implantation of a stent-graft. METHODS AND RESULTS: A 76-year-old
      man was transferred from another hospital where he had been treated for upper
      gastrointestinal hemorrhage over a 2-month period. Ten years previously, he had
      undergone aortobifemoral bypass, the right limb of which recently thrombosed. At
      the time of transfer, computed tomographic scanning showed a large false aneurysm
      between the aorta and the duodenum. Endoscopy disclosed mucosal erosions in the
      fourth portion of the duodenum. Following implantation of 2 overlapping stent
      grafts, the bleeding ceased and the false aneurysm disappeared. At no time did
      the patient have a fever. The patient initially did well, but 8 months after
      treatment, he presented with fever and chills. Recurrent infection had caused
      erosion of the aorta so that a large portion of the stent-graft was visible from
      the duodenum. The infected graft and stent-grafts were removed in a two-part
      operation, from which the patient recovered satisfactorily. CONCLUSIONS:
      Endovascular stent-grafts may have a role to play in the management of
      aortoduodenal fistula, if only as a temporary measure to control bleeding.

PMID- 10883964
TI  - Endovascular repair of an innominate artery false aneurysm following blunt
      trauma.
AB  - PURPOSE: To describe a case of endovascular graft exclusion of an innominate
      artery pseudoaneurysm arising from blunt trauma. METHODS AND RESULTS: A 21-year
      old patient was admitted following a major road accident. Computed tomography
      (CT) and aortography on admission disclosed an isolated innominate artery
      pseudoaneurysm. The lesion was stable, so an elective endoluminal repair was
      undertaken once the patient was treated for his other injuries. The right carotid
      artery was exposed and controlled, and the aneurysm was excluded by transluminal
      implantation of a customized stent-graft consisting of predilated
      polytetrafluoroethylene graft material covering a balloon-expandable Palmaz
      stent. A CT scan at 1 month and duplex scans at 6-month intervals documented good
      stent-graft positioning and aneurysm exclusion over a period of 18 months.
      CONCLUSIONS: This case illustrates the potential durability of endoluminal repair
      of innominate artery lesions and highlights the potential role of this minimally
      invasive alternative to surgery in these clinical situations.

PMID- 10883965
TI  - Endograft exclusion of residual common iliac artery aneurysms.
AB  - PURPOSE: To describe an endovascular approach for residual common iliac artery
      (CIA) aneurysm. METHODS AND RESULTS: A residual CIA was discovered in a 73-year
      old man during routine examination following straight interposition graft
      placement for a ruptured abdominal aortic aneurysm (AAA). An aortobifemoral
      bypass was performed with ligation of both aneurysmal iliac arteries. A year
      later, aneurysms of both CIA stumps were found. On each side, a Hemobahn stent
      graft was percutaneously positioned from the external to the internal iliac
      artery via the superficial femoral artery. Control angiography at 2 months and
      spiral computed tomographic angiography at 6 and 18 months confirmed exclusion of
      the aneurysms and patency of the endoprostheses. CONCLUSIONS: Successful
      endovascular treatment of residual CIA aneurysm is possible with flexible stent
      grafts.

PMID- 10883966
TI  - Detection of incremental and decremental bars at different locations across Mach
      bands and related stimuli.
AB  - Two-alternative forced-choice procedures were used to measure the detectability
      of bright and dark bars at various locations across luminance patterns that
      produced Mach bands. Detection performance was significantly affected by both
      dark and bright Mach bands: poor detection performance was observed at locations
      near, but not in, the Mach bands; relatively good detection performance at
      locations within the Mach bands was caused by reliable changes in the width,
      depth, or symmetry of the bands produced by the signal bars. The changes were
      apparent with signals of lower luminance than that needed for detection in the
      plateau regions far from the bands, but, because the cues were not sufficiently
      reliable to allow errorless performance, unusually shaped psychometric functions
      were obtained.

PMID- 10883967
TI  - Multiresolution spot detection by means of entropy thresholding.
AB  - Many imaging applications deal with the detection of small targets or spots
      embedded within an inhomogeneous background. We present a method that
      accomplishes a multiresolution detection on the wavelet-transformed image. The
      targets are separated from the background by the exploitation of Renyi's
      information, which is evaluated at the different decomposition levels of the
      wavelet transform. The scale-dependent candidate detections are successively
      combined by means of majority voting for final detection. Connections with
      results provided in different fields such as multifractal analysis, generalized
      information measures in scale-space, and cross-entropy analysis in fine-to-coarse
      transformations are discussed. Detection performance is investigated through an
      example from medical image analysis.

PMID- 10883968
TI  - Filtering and processing of panoramic images obtained using a camera and a wide
      angle-imaging reflective surface
AB  - There is an increasing interest in wide-angle imaging of the environment using
      curved reflective surfaces. With this comes the need for appropriate filtering
      and processing of the acquired images. Here we present a technique for
      homogeneous, fast filtering of panoramic images captured using a camera and a
      wide-angle-imaging reflective surface. Imaging of the panoramic environment onto
      a two-dimensional (2-D) plane necessarily introduces spatial distortions such as
      stretching and bending that vary with the viewing direction. Therefore, if the
      panoramic image is to be filtered homogeneously in all viewing directions, it is
      necessary to match the filtering to the distortions. We show how this can be
      accomplished. The image acquired by the camera is first digitally unwarped and
      represented in Cartesian coordinates representing azimuth and elevation. The
      mappings of patches of uniform size and shape on the viewsphere are then
      established. Next, for each filter patch the local mappings of great circles
      along two principal axes (along the local longitudinal and elevational
      directions) on the image plane are determined. The mappings of these great
      circles are used to perform the 2-D convolution required by the filtering
      operation. Convolution along the directions of local, mutually orthogonal great
      circles permits the filtering to be carried out in a quasi-separable fashion,
      resulting in increased computational speed and efficiency. Examples of
      homogeneous filtering using this procedure are presented.

PMID- 10883969
TI  - Iterative statistical approach to blind image deconvolution
AB  - Image deblurring has long been modeled as a deconvolution problem. In the
      literature, the point-spread function (PSF) is often assumed to be known exactly.
      However, in practical situations such as image acquisition in cameras, we may
      have incomplete knowledge of the PSF. This deblurring problem is referred to as
      blind deconvolution. We employ a statistical point of view of the data and use a
      modified maximum a posteriori approach to identify the most probable object and
      blur given the observed image. To facilitate computation we use an iterative
      method, which is an extension of the traditional expectation-maximization method,
      instead of direct optimization. We derive separate formulas for the updates of
      the estimates in each iteration to enhance the deconvolution results, which are
      based on the specific nature of our a priori knowledge available about the object
      and the blur.

PMID- 10883970
TI  - Gaussian imaging transformation for the paraxial Debye formulation of the focal
      region in a low-Fresnel-number optical system
AB  - The Debye formulation of focused fields has been systematically used to evaluate,
      for example, the point-spread function of an optical imaging system. According to
      this approximation, the focal wave field exhibits some symmetries about the
      geometrical focus. However, certain discrepancies arise when the Fresnel number,
      as viewed from focus, is close to unity. In that case, we should use the
      Kirchhoff formulation to evaluate accurately the three-dimensional amplitude
      distribution of the field in the focal region. We make some important remarks
      regarding both diffraction theories. In the end we demonstrate that, in the
      paraxial regime, given a defocused transverse pattern in the Debye approximation,
      it is possible to find a similar pattern but magnified and situated at another
      plane within the Kirchhoff theory. Moreover, we may evaluate this correspondence
      as the action of a virtual thin lens located at the focal plane and whose focus
      is situated at the axial point of the aperture plane. As a result, we give a
      geometrical interpretation of the focal-shift effect and present a brief comment
      on the problem of the best-focus location.

PMID- 10883971
TI  - Time multiplexing and parallelization in multifocal multiphoton microscopy
AB  - We investigate the imaging properties of high-aperture multifocal multiphoton
      microscopy on the basis of diffraction theory. Particular emphasis is placed on
      the relationship between the sectioning property and the distance between
      individual foci. Our results establish a relationship between the degree of
      parallelization and the axial resolution for both two- and three-photon
      excitation. In addition, we show quantitatively that if a matrix of temporal
      delays is inserted between the individual foci, it is, for the first time to our
      knowledge, possible to solve the classical conflict between the light budget and
      the sectioning property in three-dimensional microscopy and to provide a
      virtually unlimited density of foci at best axial resolution.

PMID- 10883972
TI  - Imaging of transparent spheres through a planar interface using a high-numerical
      aperture optical microscope
AB  - The details of a model used to predict the scattering of a plane polarized wave
      by a spherical particle as observed with a microscope are presented. The model
      accounts for the effect of a refractive interface on the outgoing scattered field
      and determines the image produced by a lens with high numerical aperture. The
      predictions of the model are verified by direct comparison with the
      experimentally observed scattering from polystyrene spheres in a fluid.

PMID- 10883973
TI  - Confocal microscopy of electro-optic materials: effect of aberrations on the
      axial response in ac mode
AB  - Confocal scanning optical microscopy can be used to investigate the structure of
      electro-optic materials. Application of an ac electric field allows one to
      measure sensitively small changes in the reflection of light from a sample
      surface, and those changes can be related to the electro-optic properties. We
      observe the axial dependence of the ac light intensity to be a linear combination
      of the dc component and its axial derivative. Our analysis shows that astigmatic
      aberrations and the azimuthal dependence of the optical index in anisotropic
      materials can explain this behavior.

PMID- 10883974
TI  - Effects of modulation strength in guided-mode resonant subwavelength gratings at
      normal incidence
AB  - A comparative study of the reflection spectral resonances in weakly and strongly
      modulated subwavelength gratings is presented. The effects of strong modulation
      in resonant subwavelength gratings have been largely ignored in the literature.
      We show that the spectral stability of resonances as a function of angle of
      incidence around normal can be greatly enhanced with strongly modulated gratings
      while the desirable narrow line-width associated with weakly modulated gratings
      is still maintained.

PMID- 10883975
TI  - Generalized grating imaging using an extended monochromatic light source
AB  - It is a well-known fact that one grating can act as an imaging element for
      another grating when the first is illuminated with an extended monochromatic
      light source. The conditions for image formation in such a system are studied
      when the finite size and position of the broad light source are considered. From
      the presented analysis, expressions for the location and the depth of focus of
      such images can be derived.

PMID- 10883976
TI  - Design considerations for narrow-band dielectric resonant grating reflection
      filters of finite length
AB  - An interference-waveguide approach is developed to predict the response of a
      resonant grating reflection filter and to provide a better understanding of the
      resonant process. An expression for the reflected field that accounts for all
      internal boundary reflections within the filter is developed. Under the
      assumption of an anti-reflective design, expressions characterizing the line
      shape of a filter of infinite length are first developed; then the effects of
      finite length on the response are determined. Expressions relating the length of
      the filter to the peak reflection efficiency and line width are developed. The
      degradation of the response as a function of filter length is evaluated. An
      equivalent waveguide representation is used to determine the location of the
      resonance as well as the spectral and angular linewidths of the filter. The
      minimum obtainable spectral linewidth for a filter of given length is determined
      to be on the order of deltalambda approximately lambda2/L. Rigorous analysis is
      used to verify the interference-waveguide approach.

PMID- 10883977
TI  - Blazed-binary diffractive elements with periods much larger than the wavelength
AB  - Blazed-binary optical elements with only binary ridges or pillars are diffractive
      components that mimic standard blazed-echelette diffractive elements. We report
      on the behavior of one-dimensional blazed-binary optical elements with local
      periods much larger than the wavelength. For this purpose, an approximate model
      based on both scalar and electromagnetic theory is proposed. The model is tested
      against electromagnetic-theory computational results obtained for one-dimensional
      blazed-binary gratings with large periods. An excellent agreement is obtained,
      showing that the model is able to predict quantitatively the wavelength and the
      incidence-angle dependences of the diffraction efficiency of blazed-binary
      structures.

PMID- 10883978
TI  - Measurement of Helmholtz wave fields
AB  - A simple formalism is found for the measurement of wave fields that satisfy the
      Helmholtz equation in free space. This formalism turns out to be analogous to the
      well-known theory of measurements for quantum-mechanical wave functions: A
      measurement corresponds to the squared magnitude of the inner product (in a
      suitable Hilbert space) of the wave field and a field that is associated with the
      detector. The measurement can also be expressed as an overlap in phase space of a
      special form of the Wigner function that is tailored for Helmholtz wave fields.

PMID- 10883979
TI  - Multilocalization and the van Cittert-Zernike theorem. 1. Theory
AB  - The complex degree of coherence and the resulting van Cittert-Zernike theorem are
      employed to analyze the exit of an arbitrary amplitude-division interferometer
      with two-beam interferences. Considering that the source is a periodic array of
      spatially incoherent slits and assuming negligible equivalent aberrations and no
      vignetting, an expression for the complex degree of coherence as a function of
      the position of an exit point is derived. Formulas for the location, fringe
      spacing, and fringe localization depth of the multilocalized fringes are given.

PMID- 10883980
TI  - Multilocalization and the van Cittert-Zernike theorem. 2. Application to the
      Wollaston prism
AB  - The van Cittert-Zernike theorem can be used to evaluate visibility at the exit of
      an amplitude-division interferometer with two-beam interferences. If the source
      illuminating the interferometer is a periodic array of slits, at the exit there
      is a sequence of localization surfaces. The formulas for the position and fringe
      spacing of the principal localization surfaces are applied to a Wollaston quartz
      prism, and there is good agreement between theoretical and experimental results.
      Moreover, the fringe localization depth and the intermediate localization
      surfaces obtained experimentally coincide with those predicted by theory.

PMID- 10883981
TI  - Experimental determination of the boundary condition for diffuse photons in a
      homogeneous turbid medium
AB  - We present a simple experimental method that permits an empirical determination
      of the effective boundary condition and the extrapolated end point for the
      diffuse photon density in a homogeneous turbid medium.

PMID- 10883982
TI  - Scattering of light from the random interface between two dielectric media with
      low contrast
AB  - We calculate the coherent and incoherent scattering of p- and s-polarized light
      incident from a dielectric medium characterized by a real, positive, dielectric
      constant epsilon0 onto its one-dimensional, randomly rough interface with a
      dielectric medium characterized by a real, positive, dielectric constant epsilon.
      We use a perturbation theory with a new small parameter, namely, the dielectric
      contrast eta = epsilon0 - epsilon between the medium of incidence and the
      scattering medium. The proper self-energy entering the expression for the
      reflectivity is obtained as an expansion in powers of eta through the second
      order in eta, and the reducible vertex function in terms of which the scattered
      intensity is expressed is obtained as an expansion in powers of eta through the
      fourth. The roughness-induced shifts of the Brewster angle (in p polarization)
      and of the critical angle for total internal reflection (epsilon0 > epsilon) are
      obtained. The angular dependence of the intensity of the incoherent component of
      the scattered light displays an enhanced backscattering peak, which is due to the
      coherent interference of multiply scattered lateral waves supported by the
      interface and their reciprocal partners. Analogs of the Yoneda peaks observed in
      the scattering of x rays from solid surfaces are also present. The results
      obtained by our small-contrast perturbation theory are in good agreement with
      those obtained in computer simulation studies.

PMID- 10883983
TI  - Geometrical optics model of Mie resonances
AB  - The geometrical optics model of Mie resonances is presented. The ray path
      geometry is given and the resonance condition is discussed with special emphasis
      on the phase shift that the rays undergo at the surface of the dielectric sphere.
      On the basis of this model, approximate expressions for the positions of first
      order resonances are given. Formulas for the cavity mode spacing are rederived in
      a simple manner. It is shown that the resonance linewidth can be calculated
      regarding the cavity losses. Formulas for the mode density of Mie resonances are
      given that account for the different width of resonances and thus may be adapted
      to specific experimental situations.

PMID- 10883984
TI  - Residual phase variance in partial correction: application to the estimate of the
      light intensity statistics
AB  - Although the wave-front correction provided by an adaptive optics system should
      be as complete as possible, only a partial compensation is attainable in the
      visible. An estimate of the residual phase variance in the compensated wave front
      can be used to calibrate system performance, but it is not a simple task when
      errors affect the compensation process. We propose a simple method for estimation
      of the residual phase variance that requires only the measurement of the Strehl
      ratio value. It provides good results over the whole range of compensation
      degrees. The estimate of the effective residual phase variance is useful not only
      for system calibration but also for determining the light intensity statistics to
      be expected in the image as a function of the degree of compensation introduced.

PMID- 10883985
TI  - Wave-front slope estimation
AB  - The conventional way of measuring the average slope of the phase of a wave front
      is from the centroid of the image formed at the focal plane. We show the
      limitations of using the centroid and present an optimal estimator along with the
      derivation of its lower error bound for a diffraction-limited image. The method
      is extended to slope estimation in the case of a random aberration introduced by
      atmospheric turbulence. It was found that the variance of the error of the slope
      estimator can be improved significantly at low turbulence levels by using the
      minimum mean-square-error estimator instead of the centroid.

PMID- 10883986
TI  - Control of the unilluminated deformable mirror actuators in an altitude
      conjugated adaptive optics system
AB  - Off-axis observations made with adaptive optics are severely limited by
      anisoplanatism errors. However, conjugating the deformable mirror to an optimal
      altitude can reduce these errors; it is then necessary to control, through
      extrapolation, actuators that are not measured by the wave-front sensor
      (unilluminated actuators). In this study various common extrapolation schemes are
      investigated, and an optimal method that achieves a significantly better
      performance is proposed. This extrapolation method involves a simple matrix
      multiplication and will be implemented in ALTAIR, the Gemini North Telescope
      adaptive optics system located on Mauna Kea, Hawaii. With this optimal method,
      the relative H-band Strehl reduction due to extrapolation errors is only 5%, 16%,
      and 30% when the angular distance between the guide source and the science target
      is 20, 40 and 60 arc sec, respectively. For a site such as Mauna Kea, these
      errors are largely outweighed by the increase in the size of the isoplanatic
      field.

PMID- 10883987
TI  - Vector description of higher-order modes in photonic crystal fibers
AB  - We extensively study the propagation features of higher-order modes in a photonic
      crystal fiber (PCF). Our analysis is based on a full-vector modal technique
      specially adapted to accurately describe light propagation in PCF's. Unlike
      conventional fibers, PCF's exhibit a somewhat unusual mechanism for the
      generation of higher-order modes. Accordingly, PCF's are characterized by the
      constancy of the number of modes below a wavelength threshold. An explicit
      verification of this property is given through a complete analysis of the
      dispersion relations of higher-order modes in terms of the structural parameters
      of this kind of fiber. The transverse irradiance distributions for some of these
      higher-order modes are also presented, showing an excellent agreement with recent
      experimental measurements. In the same way, the full-vector nature of our
      approach allows us to analyze the rich polarization structure of the PCF mode
      spectrum.

PMID- 10883988
TI  - Method to determine temperature distribution and intrinsic emissivity of a cavity
AB  - A method is presented to determine simultaneously the temperature distribution
      and the intrinsic emissivities of a cavity surface when radiance distributions
      along the cavity wall for two wavelengths are given. The intrinsic emissivity and
      reflection characteristics are assumed not to depend on position on the cavity
      wall. The intrinsic emissivity and reflection characteristics giving the smallest
      difference between calculated temperature distributions for the two wavelengths
      are found. The values found and thus the temperature distributions are verified
      to be close to the true ones. The method is examined on a cylindrocone by a
      simulation and applied to radiance temperature distributions measured on a
      commercially available double cone.

PMID- 10883989
TI  - Complementary roles of laparoscopic abdominal exploration and diagnostic
      peritoneal lavage for evaluating abdominal stab wounds: a prospective study.
AB  - PURPOSE: To determine the roles of laparoscopic abdominal exploration (LE) and
      diagnostic peritoneal lavage (DPL) in the evaluation of abdominal stab wounds, we
      prospectively compared LE with mandatory celiotomy (MC) in 76 patients having
      anterior abdominal stab wounds penetrating the fascia over a 22-month period.
      PATIENTS AND METHODS: Twenty-two patients underwent emergency celiotomy. The
      remaining patients were subjected to DPL and assigned to treatment by either
      celiotomy or initial LE with subsequent conversion to open exploration at the
      discretion of the attending surgeon. RESULTS: Laparotomy was avoided in 55% of
      the 31 patients undergoing initial laparoscopy, and this group demonstrated a
      significant decrease in the incidence of nontherapeutic celiotomy, from 19% to
      57% (P < 0.05), as well as decreased length of hospital stay (4 +/- 0.6 v 5.9 +/-
      0.4 days; P < 0.05), and total hospital cost ($6119 +/- 756 v $8312 +/- 627; P <
      0.05). There were no missed intraabdominal injuries or morbidity from laparoscopy
      identified in follow-up. The DPL (N = 36) was positive in 11 of the 12 patients
      with injury requiring surgical repair and was negative in 16 of the 25 patients
      not requiring repair. The sensitivity and specificity of DPL were 0.91 and 0.64
      compared with 1.0 and 0.74 for laparoscopy. CONCLUSIONS: An algorithm to evaluate
      stable patients with anterior abdominal stab wounds and minimize overall costs of
      care, incidence of nontherapeutic celiotomy, and rate of missed injuries is
      suggested consisting of DPL followed by observation in patients with negative DPL
      and by laparoscopy in patients with positive DPL. Wounds to the thoracoabdominal
      region may be best evaluated by initial LE, as diaphragmatic wounds may result in
      a false-negative DPL.

PMID- 10883990
TI  - Bupivacaine instillation into gallbladder bed after laparoscopic cholecystectomy:
      does it decrease shoulder pain?
AB  - BACKGROUND: Shoulder pain is common after laparoscopic cholecystectomy (60.5%)
      and can delay return to normal activities. The cause is unclear but may involve
      referral of pain from the traumatized area. PATIENTS AND METHODS: A total of 75
      patients with chronic cholecystitis who underwent laparoscopic cholecystectomy
      were randomized into two groups. Group I (37 patients) had 10 mL of 0.25 %
      bupivacaine instilled into the gallbladder bed and Calot's triangle area at the
      end of cholecystectomy. Group II (38 patients) served as controls and had no
      bupivacaine instillation. Postoperative shoulder pain was evaluated. RESULTS: Six
      patients in Group I developed shoulder pain (16%) compared with 23 patients in
      Group II (60.5%). The difference was statistically significant (P = 0.0002).
      CONCLUSION: The raw area of the removed organ is at least partially responsible
      for shoulder pain after laparoscopic cholecystectomy. Local bupivacaine is
      effective in reducing such pain.

PMID- 10883991
TI  - Hand-assisted laparoscopy for pelvic malignancy.
AB  - The inability to palpate intra-abdominal organs is a barrier to the widespread
      utilization of laparoscopy in the management of pelvic malignancy. Hand-assisted
      laparoscopy permits the insertion of the hand into the abdomen through a glove
      sized incision while preserving the pneumoperitoneum. This new modality preserves
      both the technical benefits of traditional manual assistance and the convalescent
      advantages of minimally invasive surgery. Our preliminary experience suggests
      that this approach is a feasible, safe, and expeditious access option that can
      effectively replace an extended open laparotomy incision or an excessively
      tedious laparoscopic exercise in the evaluation and management of pelvic
      malignancy. Moreover, oncologic surgeons, reluctant to relinquish the tactile
      advantages of open surgery, may find hand-assisted laparoscopy an appealing
      alternative.

PMID- 10883992
TI  - Laparoscopic umbilical herniorrhaphy.
AB  - BACKGROUND: Laparoscopic technique is an alternative approach to ventral hernia
      repair. This study evaluated the feasibility of performing umbilical hernia
      repair using a single 5-mm trocar technique. PATIENTS AND METHODS: During
      February 1999 to November 1999, we performed laparoscopic umbilical hernia repair
      in 16 consecutive patients. All operations were performed under general
      anesthesia. One 5-mm port was used to visualize the defect. A second 5-mm port
      was inserted only if there was incarcerated omentum requiring reduction. The Endo
      Close was inserted through a 2-mm incision made directly over the hernia to
      perform transabdominal closure of the defect using nonabsorbable suture. RESULTS:
      The mean size of the umbilical hernia defects was 1.2 cm +/- 0.4 (range 1.0-2.0
      cm). All operations were completed laparoscopically with no intraoperative or
      postoperative complications. The mean operative time was 35 +/- 15 minutes (range
      21-75 min). All cases were performed in an outpatient setting. There have been no
      recurrences at a mean follow-up of 5.9 months. CONCLUSIONS: Laparoscopic
      umbilical herniorrhaphy is safe and technically feasible. Its potential
      advantages, such as a lower rate of recurrence, will need to be validated with
      longer follow-up.

PMID- 10883993
TI  - Laparoscopy for acute small-bowel obstruction secondary to adhesions.
AB  - BACKGROUND AND PURPOSE: Postoperative adhesions are the leading cause of small
      bowel obstruction in developed countries. Several arguments suggest that
      laparoscopy may lead to fewer adhesions than does laparotomy. We report here the
      short-term results of laparoscopy in patients admitted on an emergency basis for
      acute small-bowel obstruction secondary to adhesions. PATIENTS AND METHODS: This
      prospective trial included 134 consecutive patients: 39 underwent emergency
      surgery, and 95 had laparoscopic adhesiolysis shortly after resolution of the
      obstruction with nasogastric suction. Of the previous operations for which the
      dates were known, 16% had taken place within 1 year of the obstruction and 33.5%
      within 5 years. In all, 27% of the patients had open laparoscopy, and 16% had
      conversions: 7% after elective laparoscopy and 36% after emergency laparoscopy.
      RESULTS: There were no operative deaths. One patient underwent a reoperation the
      following day for fistula after incomplete adhesiolysis attributable to multiple
      adhesions found during elective laparoscopy. If laparoscopy is considered to have
      failed when adhesiolysis was incomplete or conversion or reoperation was
      necessary, our success rate was 80% after elective laparoscopy and 59% after
      emergency laparoscopy. CONCLUSION: Emergency situations in acute small-bowel
      obstruction combine several circumstances unfavorable for laparoscopy: a limited
      work area and a distended and fragile small bowel. Laparoscopic adhesiolysis
      after the crisis has passed may produce better results, but only long-term follow
      up can confirm the role of elective laparoscopy for this indication.

PMID- 10883994
TI  - Use of minimally invasive surgery in staging esophageal cancer.
AB  - Noninvasive staging of esophageal cancer (EC) is often inaccurate, and this fact
      has compromised clinical trials of treatment for EC. Prognostic evaluation might
      allocate chemotherapy and radiation more appropriately. Thoracoscopy and
      laparoscopy has recently shown promising results, and molecular analysis of the
      recovered tissue may further improve staging accuracy.

PMID- 10883995
TI  - Simple laparoscopic ultrasound technique for prevention of bile duct injuries.
AB  - BACKGROUND: Bile duct injuries are serious complications of laparoscopic
      cholecystectomy. Laparoscopic ultrasonography (LUS) has been utilized over the
      last several years to screen for bile duct calculi and to delineate biliary
      anatomy. We have found a simple LUS scanning technique that can be useful for
      preventing bile duct injuries. METHOD: After initial scanning for screening,
      laparoscopic dissection is continued, isolating the cystic duct. If necessary,
      scanning can be performed to assure the location of the cystic duct before
      clipping. After clips are applied to the cystic duct, prior to its incision or
      transection, LUS is repeated to examine the cystic and bile ducts. RESULTS: This
      postclipping study can confirm that the clips are applied to the cystic duct and
      that the hepatic and common bile ducts are intact without occlusion. CONCLUSION:
      This additional LUS scanning maneuver is simple and quick and may help prevent
      bile duct injuries.

PMID- 10883996
TI  - Laparoscopic adrenalectomy for primary hyperaldosteronism during pregnancy.
AB  - Laparoscopic adrenalectomy was performed early in the second trimester of
      pregnancy in a woman with an aldosteronoma causing hypertension (254/154 mm Hg).
      The patient was later delivered of a healthy baby. With suitable precautions and
      timing, major laparoscopic surgery can be performed safely during pregnancy.

PMID- 10883997
TI  - Laparoscopic closure of mesenteric defects after Roux-en-Y gastric bypass.
AB  - Two case reports are presented of incarcerated small-bowel internal hernias
      through mesenteric defects following Roux-en-Y gastric bypass surgery (one case
      each of open and laparoscopic). Both patients first presented to physicians
      unfamiliar with bariatric surgery complaining of vague, cramping midabdominal
      pain, and the correct diagnosis was not revealed until laparoscopic surgery was
      performed. Treatment then resulted in quick recoveries. This type of hernia can
      evade radiologic testing. Prompt clinical recognition and treatment is necessary
      to prevent small-bowel infarction.

PMID- 10883998
TI  - The psychophysics of informal covariation assessment: perceiving relatedness
      against a background of dispersion.
AB  - The goal of 2 studies was to develop a psychophysical model of informal
      covariation assessment. The results of Experiment 1 suggest that mean covariation
      estimates are a function of the ratio of the lengths of the major and minor
      principal-components axes of correlated bivariate data. In Experiment 2,
      multidimensional scaling showed that observers perceived (a) the lengths of the
      major and minor principal-components axes and (b) the slope and dispersion of
      correlated data. The focal stimulus for mean covariation estimates was the ratio
      of the major and minor principal-components axes. Moreover, dispersion
      constituted a background context that lowered estimates somewhat. These results
      suggested a model of covariation assessment in which mean estimates were mapped
      onto a product of power transformations of the axis ratio and dispersion of
      correlated data. This model accounted for 96% of the variability in mean
      covariation estimates.

PMID- 10883999
TI  - Contrast effects do not underlie effects of preceding liquids on stop-consonant
      identification by humans.
AB  - These experiments explored the claim by A. Lotto and K. Kluender (1998) that
      frequency contrast explains listeners' compensations for coarticulation in the
      case of liquid consonants coarticulating with following stops. Evidence of
      frequency contrast in experiments that tested for it directly was not found, but
      Lotto and Kluender's finding that high- and low-frequency precursor tones can
      produce contrastive effects on stop-consonant judgments were replicated. The
      effect depends on the amplitude relation of the tones to the third formant (F3)
      of the stops. This implies that the tones mask F3 information in the stop
      consonants. It is unknown whether liquids and following stops in natural speech
      are in an appropriate intensity relation for masking of the stop. A final
      experiment, exploiting the McGurk effect, showed compensation for coarticulation
      by listeners when neither frequency contrast nor masking can be the source of the
      compensations.

PMID- 10884000
TI  - Accuracy of target detection in new-object and old-object displays.
AB  - In 4 experiments, the authors investigated accuracy of detecting a target among
      nontargets. In some experiments, the target was a second-order square of
      stationary lines on a background of downward-moving lines, and nontargets were
      second-order squares of upward-moving lines. In other experiments, target and
      nontarget squares and background were shades of gray. The principal comparison
      was between "new" and "old" object displays. In new-object displays, search items
      appeared abruptly and one might be a target. In old-object displays, search items
      appeared abruptly, and after a delay one might become a target. Search displays
      in both conditions terminated shortly after target onset. Except when target
      onset was associated with the sole luminance change in a display, targets were
      much better detected in new- than in old-object displays. It is suggested that
      object onsets elicit a brief stimulus-driven enhancement of attention to the new
      objects.

PMID- 10884001
TI  - The role of the sound of tapping for nonvisual judgment of gap crossability.
AB  - The author investigated the possibility that nonvisual locomotion with a cane
      depends on the sound of the cane tapping. Blindfolded participants were asked to
      judge whether a gap in front of them could be crossed by walking. An acoustic
      analysis suggested that sound could, in theory, distinguish the gaps. Blindfolded
      sighted participants in Experiments 1 and 2 judged crossability under conditions
      in which only the sound of tapping was available and in which the sound was
      minimized; the third and fourth experiments included experienced cane users. Both
      inexperienced observers and experienced cane users were unaffected by sound
      reduction and were less able to discriminate gaps when using sound only than when
      using reduced sound. A fifth experiment indicated that active-passive differences
      were not responsible for these effects. Results indicate that sound is not
      necessary or sufficient for judging nonvisible crossability with a probe.

PMID- 10884002
TI  - Attention-referenced visual representations: evidence from impaired visual
      localization.
AB  - Spatial representations in the visual system were probed in 4 experiments
      involving A. H., a woman with a developmental deficit in localizing visual
      stimuli. Previous research (M. McCloskey et al., 1995) has shown that A. H.'s
      localization errors take the form of reflections across a central vertical or
      horizontal axis (e.g., a stimulus 30 degrees to her left localized to a position
      30 degrees to her right). The present experiments demonstrate that A. H.'s errors
      vary systematically as a function of where her attention is focused, independent
      of how her eyes, head, or body are oriented, or what potential reference points
      are present in the visual field. These results suggest that the normal visual
      system constructs attention-referenced spatial representations, in which the
      focus of attention defines the origin of a spatial coordinate system. A more
      general implication is that some of the brain's spatial representations take the
      form of coordinate systems.

PMID- 10884003
TI  - The role of perspective effects and accelerations in perceived three-dimensional
      structure-from-motion.
AB  - It has been suggested that perceived three-dimensional (3D) structure-from-motion
      can be accounted for by a 2-frame orthographic approximation of the flow field.
      This study investigated the extent to which higher order cues (perspective and
      acceleration) are used in addition to first-order flow. Participants matched the
      3D dihedral angle of a hinged plane (probe) defined by multiple-depth cues to one
      defined by motion only, for stimulus sizes of 8 and 33 degrees, using perspective
      and orthographic projection. The results show that perspective effects can be
      important even for relatively small stimuli (8 degrees) and that accelerations
      contribute to perceived shape. In all conditions, large biases were found. These
      are well accounted for by a model in which all relevant flow measurements (first
      order, perspective, and acceleration) are used together with estimates of the
      noise in each. The model has no built-in bias toward particular 3D shapes.
      Instead, the visual system may act as an optimal estimator of 3D structure-from
      motion.

PMID- 10884004
TI  - The effects of spatial frequency overlap on face recognition.
AB  - The effects of spatial frequency overlap between pairs of low-pass versus high
      pass images on face recognition and matching were examined in 6 experiments.
      Overlap was defined as the range of spatial frequencies shared by a pair of
      filtered images. This factor was manipulated by processing image pairs with high
      pass/low-pass filter pairs whose 50% cutoff points varied in their separation
      from one another. The effects of the center frequency of filter pairs were also
      investigated. In general, performance improved with greater overlap and higher
      center frequency. In control conditions, the image pairs were processed with
      identical filters and thus had complete overlap. Even severely filtered low-pass
      or high-pass images in these conditions produced superior performance. These
      results suggest that face recognition is more strongly affected by spatial
      frequency overlap than by the frequency content of the images.

PMID- 10884005
TI  - Endogenous attention and illusory line motion reexamined.
AB  - P. Downing and A. Treisman's (1997) failure to replicate an effect of endogenous
      attention on the direction of illusory line motion (ILM) was reexamined. Four
      experiments with slightly modified stimulus presentation methods based on
      gradient theories of ILM found that endogenous attention directed to 1 of 2
      similar priming objects is capable of influencing experienced motion direction
      within a subsequently presented line. The endogenous effect on ILM was consistent
      with a concomitant response-time discrimination task, was robust across naive and
      informed participants, occurred whether eye fixation was monitored or not, and
      occurred under conditions where multiple motion response categories were
      available to participants. The endogenous effect disappeared when participants
      moved their eyes to the attended item, when there was no motivation to
      endogenously attend, and when the presentation methods of P. Downing and A.
      Treisman (1997) were used.

PMID- 10884006
TI  - Stroop and Garner effects in and out of Posner's beam: reconciling two
      conceptions of selective attention.
AB  - Space- or object-based models, on the one hand, and structural-informational
      models, on the other hand, reflect conceptually distinct approaches to visual
      selective attention. In 3 studies, the authors contrasted these approaches by
      jointly applying prototypical routines prescribed in each approach. Following a
      space-based paradigm developed by M. I. Posner, participants were cued to attend
      to a certain spatial location, and performance at expected and unexpected
      locations was compared. Following a structural paradigm developed by W. R.
      Garner, the targets were color words printed in various colors, and the
      participants responded to either the color or the word component of the stimulus.
      Performance was poorer at unexpected than at expected locations. However,
      comparable amounts of Stroop and Garner interference affected performance at both
      expected and unexpected locations. It is suggested that the processes that govern
      (a) input selection from the visual field and (b) dimensional selection from the
      stimulus reflect fundamentally different systems of attention.

PMID- 10884007
TI  - The Simon effect and its reversal in three-choice Hedge and Marsh tasks: evidence
      for irrelevant stimulus-response compatibility and stimulus congruity.
AB  - In 2-choice A. Hedge and N. W. A. Marsh (1975) tasks or S. Kornblum's (1992) Type
      5 ensembles, irrelevant stimulus-response compatibility (SRC), logical recoding,
      display control arrangement correspondence (DCC), and stimulus congruity are
      confounded. By using 3 response alternatives and both compatible and incompatible
      stimulus-response mappings, irrelevant SRC was pitted against logical recoding
      and both of them were disentangled from DCC and stimulus congruity. By varying
      response labels on a trial-by-trial basis and using different stimuli and
      responses, DCC and stimulus congruity were decoupled. Results from 4 experiments
      showed that neither logical recoding nor DCC contributes to the Simon effect and
      its reversal. Irrelevant SRC and stimulus congruity are necessary but neither is
      sufficient to account for the Simon effect and its reversal. A connectionist
      model of compatibility incorporating both irrelevant SRC and stimulus congruity
      appears to account for the results.

PMID- 10884008
TI  - The role of perceptual load in negative priming.
AB  - Negative priming (NP) effects from irrelevant distractors were assessed as a
      function of perceptual load in the processing of prime targets. Participants
      searched for a target letter among a varying number of nontarget letters in the
      center of the display and ignored an irrelevant peripheral distractor. NP from
      this distractor was found to depend on the relevant search set size, decreasing
      as this set size was increased. The authors conclude that exhausting attention in
      relevant processing reduces irrelevant processing (e.g., N. Lavie, 1995), leaving
      less distractor processing to produce NP. This conclusion is consistent with
      recent reactive inhibition views for NP (e.g., G. Houghton, S. P. Tipper, B.
      Weaver, & D. I. Shore, 1996).

PMID- 10884009
TI  - An electrophysiological study of the insertion of overt response choice.
AB  - Using electrophysiological measures, the authors studied changes in prestimulus
      state, stimulus identification, and response-related processing when, in a go/no
      go task, forced choice between 2 overt go responses was inserted. The authors
      observed decreased prestimulus motor preparation (electromyogram), no change in
      stimulus identification time (selection negativity), a minor increase in response
      selection time (lateralized readiness potential), a large increase in response
      preparation time (lateralized readiness potential), a minor effect on response
      execution time (electromyogram), and a decrease in the activation of a response
      inhibition process on no-go trials (frontal event-related potential). The
      existence of the response-inhibition process was verified by the presence of
      inverted lateralized readiness potentials on no-go trials. Pure insertion of
      response choice in a task seems impossible because the choice between activation
      and inhibition (go/no-go) always seems already present.

PMID- 10884010
TI  - Parallel memory retrieval in dual-task situations: I. Semantic memory.
AB  - Can participants retrieve information about the 2nd of 2 stimuli while they are
      processing the 1st? Four experiments suggest they can. Reaction times to the 1st
      stimulus were faster if it came from the same category as the 2nd than if it came
      from a different category. This category-match effect was observed for letter
      digit discrimination (Experiment 1), magnitude and parity judgments about digits
      (Experiment 2), and lexical decisions (Experiment 3). Experiment 4 showed that
      the 2nd stimulus could semantically prime the 1st. The category-match effect was
      observed only when the same task was performed on the 2 stimuli. When the task
      changed from the 1st stimulus to the 2nd, there was no advantage of a category
      match. This dependence on task set may explain previous failures to find parallel
      retrieval.

PMID- 10884011
TI  - Specification of movement amplitudes for the left and right hands: evidence for
      transient parametric coupling from overlapping-task performance.
AB  - Bimanual coordination tasks suggest transient cross-talk between concurrent
      specification processes for movements of the left and right hand that vanishes as
      the time for specification increases. In 2 experiments with overlapping and
      successive unimanual tasks, the hypothesis of transient coupling was examined for
      a psychological-refractory-period paradigm. Time for specification was
      manipulated by varying the delay between first and second signal (Experiment 1)
      and by precuing the first response (Experiment 2). Participants performed rapid
      reversal movements of same or different amplitudes with the left and right hands.
      With different amplitudes, reaction times (RTs) of the second responses were
      longer than with same amplitudes at short delays, and this disappeared at longer
      delays in Experiment 1. In Experiment 2, precuing also reduced the difference
      between RTs of second responses in same-amplitude and different-amplitude trials.
      These findings are consistent with the hypothesis of transient coupling during
      amplitude specification obtained with bimanual tasks.

PMID- 10884012
TI  - From vision to action: experiments and models of steering control during driving.
AB  - Experienced drivers performed simple steering maneuvers in the absence of
      continuous visual input. Experiments conducted in a driving simulator assessed
      drivers' performance of lane corrections during brief visual occlusion and
      examined the visual cues that guide steering. The dependence of steering behavior
      on heading, speed, and lateral position at the start of the maneuver was
      measured. Drivers adjusted steering amplitude with heading and performed the
      maneuver more rapidly at higher speeds. These dependencies were unaffected by a
      1.5-s visual occlusion at the start of the maneuver. Longer occlusions resulted
      in severe performance degradation. Two steering control models were developed to
      account for these findings. In the 1st, steering actions were coupled to
      perceptual variables such as lateral position and heading. In the 2nd, drivers
      pursued a virtual target in the scene. Both models yielded behavior that closely
      matches that of human drivers.

PMID- 10884013
TI  - Inertia tensor and weight-percept models of length perception by static holding.
AB  - S. J. Lederman, S. R. Ganeshan, and R. E. Ellis (1996) reported an experiment
      demonstrating that for occluded rods of equal mass and length but different
      diameters length perception by static holding was larger for rods of smaller
      diameter. They concluded that participants inferred length from illusory weight
      percepts. However, rods of equal mass and length that differ in diameter also
      differ in the eigenvalues of their respective inertia tensors. In the present
      experiments, the authors manipulated the diameters (Experiment 1) and the
      inertial eigenvalues (Experiments 4 and 5) of statically held objects. As has
      been shown with wielded objects, perceived length was a function of the
      eigenvalues. Additional experiments failed to confirm the expectation from the
      weight-percept model that perceived length maps to the estimated weight
      (Experiments 2 and 3). Physical quantities, not psychological quantities, seem to
      explain length perception by static holding.

PMID- 10884014
TI  - Walking infants adapt locomotion to changing body dimensions.
AB  - Infants acquire independent mobility amidst a flux of body growth. Changes in
      body dimensions and variations in the ground change the physical constraints on
      keeping balance. The study examined whether toddlers can adapt to changes in
      their body dimensions and variations in the terrain by loading them with lead
      weights and observing how they navigated safe and risky slopes. Experiment 1
      verified the reliability of a new psychophysical procedure for testing infants'
      responses in 2 experimental conditions. In Experiment 2, this procedure was used
      to compare infants' responses on slopes in feather-weight and lead-weight
      conditions. The lead weights impaired infants' ability to walk down slopes.
      Babies adapted to altered body dimensions by treating the same degree of slope as
      safe in the feather-weight condition but as risky in the lead-weight condition.
      Exploratory activity on the starting platform predicted adaptive responses on
      risky slopes.

PMID- 10884015
TI  - Mixed reference frames for dynamic inhibition of return.
AB  - Reference frames mediating inhibition of return (IOR) in dynamic displays were
      investigated by comparing the effects of a cue in simple versus extended objects.
      Experiment 1 replicated S. P. Tipper, B. Weaver, L. M. Jerreat, and A. L. Burak's
      (1994) finding of location- and object-based IOR for boxes rotating about
      fixation. In Experiments 2 and 3, the boxes were replaced by two boomerang-shaped
      objects. Response times were slowed to all target locations across a cued object.
      They were also slowed to locations vacated by the uncued region of the cued
      object-evidence for a representation the authors call the "perceptual footprint."
      Whereas an object served as the medium for location-based IOR for B. S. Gibson
      and H. Egeth (1994), the environment served as the medium for object- and
      location-based IOR in Experiments 2 and 3. This suggests that (a) frames of
      reference may be considered hierarchically and (b) nesting of frames is context
      dependent.

PMID- 10884016
TI  - Reading aloud begins when the computation of phonology is complete.
AB  - Naming latency experiments in which monosyllabic items are read aloud are based
      on the assumption that the vocal response is not initiated until the phonology of
      the entire syllable has been computed. Recently, this assumption has been
      challenged by A. H. Kawamoto, C. T. Kello, R. Jones, and K. Bame (1998), who
      argued instead that the reading-aloud response begins as soon as the initial
      phoneme is computed. This view would be refuted by evidence of anticipatory
      coarticulation effects on the initial phoneme due to the nature of the following
      vowel in the speeded reading-aloud task. The authors provide such evidence.

PMID- 10884017
TI  - Lateralized word recognition: assessing the role of hemispheric specialization,
      modes of lexical access, and perceptual asymmetry.
AB  - The processing advantage for words in the right visual field (RVF) has often been
      assigned to parallel orthographic analysis by the left hemisphere and sequential
      by the right. The authors investigated this notion using the Reicher-Wheeler task
      to suppress influences of guesswork and an eye-tracker to ensure central
      fixation. RVF advantages obtained for all serial positions and identical U-shaped
      serial-position curves obtained for both visual fields (Experiments 1-4). These
      findings were not influenced by lexical constraint (Experiment 2) and were
      obtained with masked and nonmasked displays (Experiment 3). Moreover, words and
      nonwords produced similar serial-position effects in each field, but only RVF
      stimuli produced a word-nonword effect (Experiment 4). These findings support the
      notion that left-hemisphere function underlies the RVF advantage but not the
      notion that each hemisphere uses a different mode of orthographic analysis.

PMID- 10884018
TI  - Visual perception of mean relative phase and phase variability.
AB  - Perception of relative phase and phase variability may play a fundamental role in
      interlimb coordination. This study was designed to investigate the perception of
      relative phase and of phase variability and the stability of perception in each
      case. Observers judged the relative phasing of two circles rhythmically moving on
      a computer display. The circles moved from side to side, simulating movement in
      the frontoparallel plane, or increased and decreased in size, simulating movement
      in depth. Under each viewing condition, participants observed the same displays
      but were to judge either mean relative phase or phase variability. Phase
      variability interfered with the mean-relative-phase judgments, in particular when
      the mean relative phase was 0 degrees. Judgments of phase variability varied as a
      function of mean relative phase. Furthermore, the stability of the judgments
      followed an asymmetric inverted U-shaped relation with mean relative phase, as
      predicted by the Haken-Kelso-Bunz model.

PMID- 10884019
TI  - Graded effects in hierarchical figure-ground organization: reply to Peterson
      (1999).
AB  - An important issue in vision research concerns the order of visual processing. S.
      P. Vecera and R. C. O'Reilly (1998) presented an interactive, hierarchical model
      that placed figure-ground segregation prior to object recognition. M. A. Peterson
      (1999) critiqued this model, arguing that because it used ambiguous stimulus
      displays, figure-ground processing did not precede object processing. In the
      current article, the authors respond to Peterson's (1999) interpretation of
      ambiguity in the model and her interpretation of what it means for figure-ground
      processing to come before object recognition. The authors argue that complete
      stimulus ambiguity is not critical to the model and that figure-ground precedes
      object recognition architecturally in the model. The arguments are supported with
      additional simulation results and an experiment, demonstrating that top-down
      inputs can influence figure-ground organization in displays that contain stimulus
      cues.

PMID- 10884020
TI  - Serial processing in reading aloud: reply to Zorzi (2000).
AB  - K. Rastle and M. Coltheart (1999; see also M. Coltheart & K. Rastle, 1994)
      reported data demonstrating that the cost of irregularity in reading aloud low
      frequency exception words is modulated by the position of the irregularity in the
      word. They argued that these data implicated a serial process and falsified all
      models of reading aloud that operate solely in parallel, a conclusion that M.
      Zorzi (2000) challenged by successfully simulating the position of irregularity
      effect with such a model. Zorzi (2000) further claimed that a reanalysis of K.
      Rastle and M. Coltheart's (1999) data demonstrates sensitivity to grapheme
      phoneme consistency (which he claimed was confounded across the position of
      irregularity manipulation) rather than the use of a serial process. Here, the
      authors argue that M. Zorzi's (2000) reanalyses were inappropriate and reassert
      that K. Rastle and M. Coltheart's (1999) findings are evidence for serial
      processing.

PMID- 10884021
TI  - Is nuclear factor-kappaB a good treatment target in brain ischemia/reperfusion
      injury?
AB  - Nuclear factor-kappaB (NF-kappaB) is a transcription factor which resides in its
      unactivated form in the cytoplasm. Following activation subsequent to cerebral
      ischemia and reperfusion injury, NF-kappaB acts on genes for cytokines, adhesion
      molecules, nitric oxide synthase, cyclooxygenase-2, metalloproteinase-9, and
      perhaps apoptotic genes. These genes have a variety of positive and negative
      influences on the outcome of brain injury. The effect of manipulation of NF
      kappaB needs to be examined critically, as it pertains to these reactive genes.

PMID- 10884022
TI  - Striatal enkephalin gene expression does not reflect parkinsonian signs.
AB  - Loss of striatal dopamine has been associated with an increase in striatal
      enkephalin expression. However, the relationship between increased striatal
      enkephalin expression and the manifestation of parkinsonian motor deficits is not
      clear. Administration of MPTP to cats produces a severe parkinsonian condition
      from which the animals spontaneously recover. Using in situ hybridization
      histochemistry, preproenkephalin (PPE) mRNA expression was examined in the
      striatum of cats when normal, symptomatic for or spontaneously recovered from
      MPTP-induced parkinsonism. In all areas of the striatum, PPE mRNA levels were
      significantly elevated in animals exhibiting severe parkinsonian motor deficits
      and remained elevated even after recovery of gross motor functioning. These
      results show that striatal PPE gene expression and parkinsonian motor deficits
      are not directly correlated.

PMID- 10884023
TI  - Melatonin limits transcriptional impact of phosphoCREB in the mouse SCN via the
      Mel1a receptor.
AB  - In the mouse, activity phase-shifts of the endogenous clock in the
      suprachiasmatic nucleus (SCN) are associated with phosphorylation of the
      transcription factor Ca2+/cAMP responsive element binding protein (CREB). CREB
      phosphorylation is induced by the retino-hypothalamic transmitter pituitary
      adenylate cyclase-activating polypeptide (PACAP). As detected by
      immunohistochemistry in SCN slices from wild-type mice, melatonin completely
      blocked PACAP-stimulated CREB phosphorylation at low concentrations (1 nM). In
      Mel1a melatonin receptor-deficient mice, the PACAP-induced CREB phosphorylation
      was inhibited only at melatonin concentrations of 100 nM. This inhibition was,
      however, blunted by blocking the Mel1b melatonin receptor. Thus, melatonin
      modulates PACAP-mediated retinal stimuli for clock entrainment primarily via the
      Mel1a melatonin receptor through molecular interaction within the cAMP-signalling
      pathway.

PMID- 10884024
TI  - Odors regulate Arc expression in neuronal ensembles engaged in odor processing.
AB  - Synaptic activity is critical to developmental and plastic processes that produce
      long-term changes in neuronal connectivity and function. Genes expressed by
      neurons in an activity-dependent fashion are of particular interest since the
      proteins they encode may mediate neuronal plasticity. One such gene encodes the
      activity-regulated cytoskeleton-associated protein, Arc. The present study
      evaluated the effects of odor stimulation on Arc expression in rat olfactory
      bulb. Arc mRNA was rapidly increased in functionally linked cohorts of neurons
      topographically activated by odor stimuli. These included neurons surrounding
      individual glomeruli, mitral cells and transynaptically activated granule cells.
      Dendritic Arc immunoreactivity was also increased in odor-activated glomeruli.
      Our results suggest that odor regulation of Arc expression may contribute to
      activity-dependent structural changes associated with olfactory experience.

PMID- 10884025
TI  - Enhanced GAP-43 gene expression in cortical dysplasia.
AB  - Growth-associated protein GAP-43, a phosphoprotein enriched at presynaptic nerve
      terminals, is thought to be involved in axonal outgrowth and plasticity in
      synaptic connections. To explore the synaptic remodeling under the epileptic
      conditions, we examined GAP-43 expression in brain specimens surgically resected
      as epileptogenic foci from 17 patients with cortical dysplasia. In situ
      hybridization with GAP-43 antisense riboprobe showed significantly increased
      signals in the dysplastic large neurons of cortical dysplasia. Specific
      distribution with increased immunoreactivity for GAP-43 was not shown in the
      dysplastic cortex. These results suggest that GAP-43 gene expression is over
      expressed in the dysplastic large neurons, reflecting activated synaptic
      remodeling in the epileptic condition of cortical dysplasia, although the precise
      site of accelerated synaptic rearrangement remains unknown.

PMID- 10884026
TI  - Secretory activity and serotonin innervation of subcommissural organ.
AB  - We investigated immunohistochemically the subcommissural organ (SCO) glycoprotein
      secretion, its serotoninergic (5-HT) innervation and the possible control of this
      innervation upon the SCO activity in lizards (Agama impalearis, Saurodactylus
      mauritanicus and Eumeces algeriensis). Inside the SCO, interspecific differences
      in the intensity and the distribution of both secretary product and 5-HT nerve
      fibers were observed. Compared with Agama and Eumeces, the SCO of Saurodactylus
      displayed intense secretory products and several 5-HT fibers. In Saurodactylus,
      i.p. injection of parachlorophenylalanine, a potent inhibitor of 5-HT synthesis,
      produced a marked decrease of SCO secretory product. We report in this study
      species differences of the lizard SCO secretory activity and its possible
      physiological control by 5-HT innervation, as previously demonstrated in mammals.

PMID- 10884027
TI  - Cytosolic 5'-nucleotidase hyperactivity in erythrocytes of Lesch-Nyhan syndrome
      patients.
AB  - Lesch-Nyhan syndrome is a metabolic-neurological syndrome caused by the X-linked
      deficiency of the purine salvage enzyme hypoxanthine-guanine
      phosphoribosyltransferase (HGPRT). Metabolic consequences of HGPRT deficiency
      have been clarified, but the connection with the neurological manifestations is
      still unknown. Much effort has been directed to finding other alterations in
      purine nucleotides in different cells of Lesch-Nyhan patients. A peculiar finding
      was the measure of appreciable amount of Z-nucleotides in red cells. We found
      significantly higher IMP-GMP-specific 5'-nucleotidase activity in the
      erythrocytes of seven patients with Lesch-Nyhan syndrome than in healthy
      controls. The same alteration was found in one individual with partial HGPRT
      deficiency displaying a severe neurological syndrome, and in two slightly
      hyperuricemic patients with a psychomotor delay. Since ZMP was a good substrate
      of 5'-nucleotidase producing Z-riboside, we incubated murine and human cultured
      neuronal cells with this nucleoside and found that it is toxic for our models,
      promoting apoptosis. This finding suggests an involvement of the toxicity of the
      Z-riboside in the pathogenesis of neurological disorders in Lesch-Nyhan syndrome
      and possibly in other pediatric neurological syndromes of uncertain origin.

PMID- 10884028
TI  - Creatine reduces 3-nitropropionic-acid-induced cognitive and motor abnormalities
      in rats.
AB  - This study assessed whether creatine could attenuate 3-nitropropionic acid (3NP)
      induced neuropathological and behavioral abnormalities that are analogous to
      those observed in Huntington's disease (HD). Rats were fed diets containing
      either 1% creatine or normal rat chow for 2 weeks prior to the onset of 3NP
      administration, and for the duration of the study. 3NP was administered
      systemically in gradually increasing concentrations over an 8-week testing
      period. Results show that creatine can attenuate 3NP-induced striatal lesions,
      striatal atrophy, ventricular enlargement, cognitive deficits, and motor
      abnormalities on a balance beam task. Collectively, these findings indicate that
      creatine provides significant protection against 3NP-induced behavioral and
      neuropathological abnormalities and may have therapeutic potential for HD.

PMID- 10884029
TI  - Acute treatments with GMP produce antidepressant-like effects in mice.
AB  - This study examined the effect of GMP in two models of depression in mice. The
      immobility times in the forced swimming test (FST) and in the tail suspension
      test (TST) were significantly reduced by GMP (dose range: 5-50 mg/kg and 5-100
      mg/kg, i.p., respectively), without accompanying changes in ambulation in an open
      field. I.c.v. injection of GMP (320-480 nmol/site) also reduced the immobility in
      the FST without affecting ambulation. The immobility of mice treated with MK-801
      (0.01 mg/kg) + GMP (50 mg/kg) was not significantly different from the result
      obtained with MK-801 or GMP alone, but GMP (or MK-801) + imipramine (15 mg/kg)
      treatment induced a stronger effect in FST than administration of either drug
      alone. Pretreatment with p-chlorophenylalanine (100 mg/kg, 4 days) completely
      blocked the anti-immobility effect of GMP, MK-801 or fluoxetine (32 mg/kg), but
      only partially that of imipramine in the FST. The results suggest that the
      antidepressant-like effects produced by the administration of GMP, like MK-801,
      may be due to an indirect serotonin activation resulting from blockade of NMDA
      receptors.

PMID- 10884030
TI  - 6-Aminonicotinamide inhibition of the pentose phosphate pathway in rat neocortex.
AB  - 6-Aminonicotinamide (6-AN) is thought to inhibit the pentose phosphate pathway
      (PPP) since large increases in 6-phosphogluconate are observed following its
      administration. Immediately following 45 min i.v. infusion of [2-(13)C]glucose to
      controls and 6-AN-treated (50 mg/kg i.p. given 4 h previously) Sprague-Dawley
      rats (n = 5 for both groups), metabolism was arrested using freeze-funnel
      fixation. Chloroform-methanol-water neocortical extracts from animals
      administered with 6-AN demonstrated elevated levels of 6-phosphogluconate and 6
      phosphoglucono-delta-lactone, both of which demonstrated labeling through
      metabolism of [2-(13)C]glucose. Comparison of the C-2 and C-3 lactate positions
      using 1H NMR spectroscopy showed that the fraction of glucose metabolized through
      the PPP is unchanged by 6-AN (14+/-0.6% vs 14+/-0.3% in control animals). It is
      hypothesized that as the PPP is inhibited by metabolites of 6-AN in the
      neocortex, glycolysis is inhibited in a proportionate manner through an
      inhibitory effect on phosphoglucose isomerase by 6-phosphogluconate and/or 6
      phosphoglucono-delta-lactone.

PMID- 10884031
TI  - New insights into the Stroop effect: a spatio-temporal analysis of electric brain
      activity.
AB  - Recent clinical and imaging studies suggest the involvement of anterior brain
      regions in the Stroop effect without providing consensus on the hemisphere being
      involved. Here, we investigated the dynamics of brain activation during a
      modified Stroop task using behavioural, event-related potential map series, and
      source localization analysis. Behavioural analysis showed an increased RT in the
      interference (IC) as compared to the neutral (NC) and congruence conditions (CC).
      Map series analysis in these conditions displayed a similar sequence of 10 stable
      segments. From these, only segment S6, occurring at approximately 300 ms and
      displaying a dominant right anterior activation, was of increased duration in IC.
      Furthermore, in IC only, RT was shown to correlate with S6 duration. These
      results are discussed in terms of increased duration of an attentional process
      needed to solve the conflict.

PMID- 10884032
TI  - Adenoviral vector-mediated GDNF gene transfer prevents death of adult facial
      motoneurons.
AB  - We examined neuroprotective effects of an adenoviral vector encoding glial cell
      line-derived neurotrophic factor (AxCAhGDNF) on the lesioned adult rat facial
      motoneurons. After facial nerve avulsion, animals locally injected into the
      facial canal with AxCALacZ (adenovirus encoding beta-galactosidase gene) or
      AxCAhGDNF showed expression of beta-galactosidase activity or intense
      immunolabeling for GDNF in lesioned facial motoneurons, respectively. The
      treatment with AxCAhGDNF after avulsion significantly prevented the loss of
      lesioned facial motoneurons, ameliorated choline acetyltransferase
      immunoreactivity, and suppressed the activity of nitric oxide synthase in these
      neurons. These results indicate that the adenovirus-mediated gene transfer of
      GDNF may prevent the degeneration of motoneurons in adult humans with peripheral
      nerve injury and motor neuron diseases.

PMID- 10884033
TI  - Event-related potentials in a self-paced novelty oddball task.
AB  - The event-related potentials (ERPs) to the stimuli triggered by a participant's
      self-paced key press were compared with the ERPs to the same stimuli presented at
      an external pace. Fourteen participants responded to 2000 Hz target tones
      interspersed among 1000 Hz standard tones and various unique novel sounds. The
      amplitudes of the P3s elicited by target and novel stimuli were larger in the
      self-triggered condition than in the machine-triggered condition in which the
      stimuli were presented automatically with the same intervals as in the self
      triggered condition. The effect was prominent at fronto-central scalp sites. When
      the timing of stimulus is unequivocal, a neural activity related to stimulus
      evaluation may increase and manifest itself as a large late positive ERP
      component.

PMID- 10884034
TI  - NT2 neurons, a classical model for Alzheimer's disease, are highly susceptible to
      oxidative stress.
AB  - We have tested undifferentiated NT2 cells as well as differentiated NT2 neurons
      (NT2N) for vulnerability to oxidative stress, lipid composition and antioxidant
      pattern. NT2N, but not NT2 cells, are highly susceptible to oxidative stress
      elicited by different classic pro-oxidant stimuli. In particular, NT2N cells
      undergo a high level of oxidative decomposition of omega-3 and omega-6
      polyunsaturated fatty acids (PUFA) of membrane phospholipids, as evaluated by
      monitoring generation of thiobarbituric reactive substances, 4-hydroxynonenal
      (HNE) and chromolipid fluorescent adducts. NT2N cells exhibit low levels of
      natural antioxidants such as glutathione (GSH) and alpha-tocopherol and of
      antioxidant enzymatic activities such as Se-dependent GSH peroxidase and
      catalase. Accordingly, a direct correlation between lipid peroxidation and
      irreversible cell damage is suggested by prevention of NT2N cell death by alpha
      tocopherol.

PMID- 10884035
TI  - Modulation of event-related potentials by prototypical and atypical faces.
AB  - High-density event-related potentials (HD-ERPs) were recorded while adults
      passively viewed colour images of faces that artificially (Experiment I) or
      naturally (Experiment II) differed in configuration. In Experiment I, altering
      features of faces to make them less typical and less attractive did not affect
      the amplitude of N170, but did affect the amplitude of P1 and P2. In Experiment
      II, the P1 and N170 were larger for unattractive and atypical faces compared with
      attractive and typical faces, in the absence of P2 effects. The results show for
      the first time that variations in facial configuration modulate ERP activity as
      early as P1, but that modulation of later latency components depends on the
      nature of the stimuli and implicit task demands.

PMID- 10884036
TI  - Regulation of expression of nuclear factor kappa B RelA in oligodendrocytes:
      effect of hypoxia.
AB  - Little is known about the expression of nuclear factor kappa B (NF-kappaB) in
      oligodendrocytes. We demonstrate that under normal culture conditions only 21% of
      oligodendrocytes express NF-kappaB p65; exposure to hypoxia increased this to
      69%. A similar increase in total p65 was seen with Western blots. Northern blot
      analysis demonstrated that NF-kappaB p65 mRNA increased during the first few h
      following hypoxia, suggesting that exposure to hypoxia affects NF-kappaB p65
      transcription or p65 mRNA stability. Under normoxic conditions only 2% of the
      oligodendrocytes exhibited activated NF-kappaB; this was increased to 8% by
      hypoxia followed by reoxygenation. Despite activation of NF-kappaB, no detectable
      expression of the pro-inflammatory genes iNOS and ICAM-1 was seen. This is the
      first demonstration that hypoxia can up-regulate p65.

PMID- 10884037
TI  - Attentive and pre-attentive periodicity analysis in auditory memory: an event
      related brain potential study.
AB  - In an event-related potential (ERP) study we presented human subjects with
      streams of repetitive white noise (semi-periodic noise) under attend and ignore
      conditions to investigate whether the perception of the periodicity with short
      cycle-lengths is due to lower level, pre-attentive sensory memory processing or
      higher level, attentive working memory processing. The ERPs of both conditions
      reveal N1-like deflections that are time locked on the semi-periodic noise
      suggesting that the processing of the periodicity is due to a pre-attentive
      rather than an attentive process. The topography of the deflections suggests that
      its generators are located in the supratemporal plane. Additionally, the ERPs
      elicited by infrequent disruptions in the periodicity show differences between
      the conditions suggesting that the detection of disruptions in periodicity is
      facilitated by attention.

PMID- 10884038
TI  - The barrel field of the adult mouse SmI cortex as revealed by NADPH-diaphorase
      histochemistry.
AB  - The main goal of the present work was to investigate the pattern of NADPH
      diaphorase activity in the somatosensory cortex of the adult mouse. Our results
      show that this enzyme, which is responsible for the production of the neuronal
      messenger nitric oxide, is abundant within the neuropil of SmI cortex, revealing
      the complete pattern of barrel fields. A previous study, however, had reported
      that NADPH-diaphorase reactivity within the barrels was transient, disappearing
      after the second postnatal week. We hypothesize that the massive occurrence of
      NADPH-diaphorase in the barrel fields of the adult mouse brain is related to the
      potential for plastic changes in the somatosensory cortex that is maintained
      throughout maturity.

PMID- 10884040
TI  - Cognitive bias induced by visuo-motor adaptation to prisms: a simulation of
      unilateral neglect in normal individuals?
AB  - Unilateral neglect has been recently shown to be improved following a short
      period of adaptation to wedge prisms. The present study investigates whether
      visuo-motor adaptation can generate a bias in normals on line bisection tasks
      classically used to assess unilateral neglect. Our results show that adaptation
      to left-deviating prisms induces a stronger rightward bias for the perceptual
      than the motor line bisection task. This bias is in the same direction as the one
      observed in unilateral neglect. No significant effect is produced by adaptation
      to right-deviating prisms. Our data confirm that the plasticity of inter-sensory
      and sensori-motor coordinations affects higher levels of space representation.
      These asymmetric results may reflect the inherent bias of the brain's structural
      organisation and provide an empirical explanation for the left-sided predominance
      of unilateral neglect.

PMID- 10884039
TI  - Evidence for an association between a G-protein beta3-gene variant with
      depression and response to antidepressant treatment.
AB  - Abnormal signal transduction pathways have been implicated in the pathogenesis of
      bipolar disorder and major depression. G-proteins are key elements of these
      pathways in the regulation of cellular responses by transmission of signals from
      receptors to effector proteins. In recent years several studies have reported
      altered levels and activities of G-protein alpha subunits in depressive patients.
      A recently identified polymorphism of a G-protein beta3 subunit (C825T) has been
      shown to be associated with increased signal transduction and ion transport
      activity. Therefore, we investigated whether this Gbeta3 polymorphism is
      associated with affective disorders or with the response to antidepressant
      treatment in 88 depressive patients (10 bipolar disorder, 78 major depression)
      compared with 68 schizophrenic patients and 111 healthy controls. We found a
      significantly higher frequency of the T allele in depressive patients than in
      healthy controls (genotype: chi2 = 9.571, df = 2, p = 0.008; alleles: p = 0.004,
      OR = 1.87, 95% CI 1.23-2.84; Fisher's exact test, two sided) and schizophrenic
      patients (genotype: chi2 = 8.037, df = 2, p = 0.018; alleles: p = 0.009, OR =
      1.94, 95% CI 1.99-3.14; Fisher's exact test, two sided). We also found a
      statistical significant association between TT homozygosity and response to
      antidepressant treatment after four weeks (p = 0.01). The results of this study
      suggest that the investigated G-protein beta3 subunit seems to be a
      susceptibility factor for major depression and maybe even for bipolar disorder,
      but not for schizophrenia. Further, the presence of the T allele could be an
      indicator for treatment response.

PMID- 10884042
TI  - Location of the human frontal eye field as defined by electrical cortical
      stimulation: anatomical, functional and electrophysiological characteristics.
AB  - Electrical cortical stimulation of the human frontal gyri and the precentral
      gyrus has been shown to induce eye movements and it has classically been assumed
      that these stimulation-induced eye movements result from electrical interference
      with the human homologue of the monkey frontal eye field (FEF). However,
      amplitude of electrical current and induced type of eye movement, which are
      essential for the determination of eye fields in the monkey, have not been
      investigated systematically in man. We applied electrical cortical stimulation in
      the lateral frontal cortex in six epileptic patients. Sites whose stimulation
      resulted in eye movements were determined with respect to gyral and sulcal
      patterns, Talairach coordinates and neighboring functions as found by electrical
      cortical stimulation. Based on this approach, a restricted location of the
      electrically defined FEF is proposed within a larger oculomotor region on the
      posterior part of the middle frontal gyrus.

PMID- 10884041
TI  - Sluggish auditory processing in dyslexics is not due to persistence in sensory
      memory.
AB  - The hypothesis that dyslexics show prolonged audible persistence was tested by an
      event-related brain response technique and rejected in favour of an attentional
      explanation.

PMID- 10884043
TI  - Activity-induced plasticity in brain stem pain modulatory circuitry after
      inflammation.
AB  - Brain stem descending pathways modulate spinal nociceptive transmission. In a
      lightly anesthetized rat preparation, we present evidence that such descending
      modulation undergoes time-dependent changes following persistent hindpaw
      inflammation. There was an initial decrease and a subsequent increase in the
      excitability of neurons in the rostral ventromedial medulla (RVM) involving
      facilitation and inhibition. These changes were most robust after stimulation of
      the inflamed paw although similar findings were seen on the non-inflamed paw and
      tail. The enhanced descending modulation appeared to be mediated by changes in
      the activation of the NMDA excitatory amino acid receptor. These findings
      demonstrate the dynamic plasticity of the pain modulating pathways in response to
      persistent tissue injury.

PMID- 10884044
TI  - Vestibular compensation modifies the sensitivity of vestibular neurones to
      inhibitory amino acids.
AB  - The progressive disappearance of the postural and oculomotor syndrome triggered
      by unilateral labyrinthectomy (vestibular compensation) is a model of plasticity
      in the adult central nervous system. This recovery may involve modifications of
      the pharmacological profile of central vestibular neurones, in particular their
      sensitivity to inhibitory amino acids. We therefore compared the sensitivity of
      medial vestibular nucleus neurones to glycine and muscimol in slices taken either
      from control animals, or from guinea-pigs labyrinthectomized 3 days before. We
      demonstrate that the loss of excitatory inputs experienced by the ipsilesional
      vestibular neurones induces a decrease in their sensitivity to inhibitory amino
      acids. These pharmacological changes should facilitate the recovery of a normal
      balance between the average resting discharge of neurones in both vestibular
      nuclei.

PMID- 10884045
TI  - Sleep deprivation stimulates serotonin release in the suprachiasmatic nucleus.
AB  - Recent literature suggests that sleep deprivation has a general stimulatory
      effect on the central serotonergic system. Herein we report that in hamsters,
      sleep deprivation induced by gentle handling for 3 h under dim red light at
      midday stimulates serotonin release in the suprachiasmatic nuclei by as much as
      171%. Basal levels of 5-HT release are re-established within 1 h after cessation
      of treatment. Sleep deprivation also evokes phase advances of the circadian
      activity rhythm averaging 2 h. When sleep deprivation is undertaken in bright
      light, serotonin release is stimulated, but phase-shifting is greatly inhibited.
      It is therefore proposed that if the phase-resetting response to sleep
      deprivation is mediated by increased serotonin release, light inhibits the phase
      resetting effect by blocking the postsynaptic or other downstream actions of
      serotonin.

PMID- 10884046
TI  - Astrocytic alteration induced by Japanese encephalitis virus infection.
AB  - The neurotropism of Japanese encephalitis virus (EV) has not been well
      characterized. Astrocytes are parts of the blood-brain barrier, a major source of
      chemokines, and critical effectors of central inflammation. Thus, astrocytes
      might play some role as JEV travels from the peripheral to the CNS and/or the
      resultant encephalitis. Using rat cortical cultures, we found that JEV can cause
      cellular and/or functional changes in astrocytes as indicated by increased
      expression of interleukin-6 (IL-6), regulated by activation, normal T cell
      expressed and secreted (RANTES), and monocyte chemotactic protein 1 (MCP-1),
      increased lactate release and glucose uptake, and attenuation of glutamate
      toxicity. These modulations occur needed by the cells for compensation and may
      affect neuron and/or astrocyte function.

PMID- 10884047
TI  - Nociceptin prevents stress-induced ethanol- but not cocaine-seeking behavior in
      rats.
AB  - This study examined whether nociceptin/orphanin FQ (NC), the endogenous ligand of
      the opioid receptor-like1 (ORL1) receptor, can block drug-seeking behavior
      induced by foot-shock stress. Male Wistar rats were trained to operantly self
      administer ethanol or cocaine, and then subjected to daily extinction training
      until responding ceased. Subsequent exposure to 15 min of intermittent footshock
      elicited robust reinstatement of responding at the previously drug-paired lever.
      NC (0.1-2.0 microg; i.c.v.) significantly inhibited the effects of footshock
      stress on ethanol- but not cocaine-seeking behavior. The results support the
      hypothesis that the NC system participates in the regulation of behavioral
      responses to stress, and that drugs interacting with NC receptors may have
      therapeutic potential for the treatment of stress-induced alcohol-seeking
      behavior and relapse.

PMID- 10884048
TI  - TENS modulates spatial reorientation in neglect patients.
AB  - The existence of separate systems for processing geometric and non-geometric
      spatial information was studied. Twelve neglect patients were asked to reorient
      themselves in a room using only geometric information or to integrate this
      information with relevant visual cues both in the presence and in the absence of
      transcutaneous electrical neural stimulation (TENS). In the absence of TENS, all
      patients were greatly impaired in coding geometric information, and they had
      difficulty in coding non-geometric information. TENS significantly improved the
      ability to code shape-based representation, but is ineffective with non-geometric
      representations (such as color). The data support previous findings on neglect
      patients suggesting the presence of separate, independent neural systems
      subserving different types of space representation.

PMID- 10884049
TI  - Interacting effects of capsaicin and anandamide on intracellular calcium in
      sensory neurones.
AB  - Capsaicin (100 nM to 1 microM) and anandamide (200 nM to 10 microM) caused a
      transient increase in fluorescence of fura-2 loaded cultured small trigeminal
      neurones of rats measured with a ratiometric technique. The percentage of cells
      responding to capsaicin at 100 nM, 330 nM and 1 microM was 47.4%, 45.3%, and
      70.4%, respectively. Averaged peak value of fluorescense ratio (R) at 340 and 380
      nm excitation was slightly dose dependent. Peaks of anandamide-induced transients
      were R = 0.2 at 200 nM and 0.16 at 10 microM. Near 40% of capsaicin-sensitive
      cells responded also to anandamide. Anandamide (200 nM) inhibited the capsaicin
      induced calcium influx. The results suggest that anandamide increases
      intracellular calcium and inhibits capsaicin-evoked calcium transients.

PMID- 10884050
TI  - Immunohistochemical localization of the carboxy terminus of the novel mu opioid
      receptor splice variant MOR-1C within the human spinal cord.
AB  - The present study examined the distribution in the human spinal cord of a unique
      carboxy terminus sequence contained within MOR-1C, one of the recently described
      splice variants of the cloned mu opioid receptor gene MOR-1. Although MOR-1-like
      immunoreactivity (LI) and delta opioid receptor-like immunoreactivity were
      observed only in the superficial laminae, MOR-1C-LI was abundant in the
      superficial laminae of the dorsal horn and around the central canal. In the
      substantia gelatinosa, MOR-1C-LI was found in small diameter axonal elements, the
      cytoplasm and the plasmalemma of small spinal neurons and dendrites in inner
      lamina II and in some fibers within Lissauer's tract. These studies imply the
      presence of MOR-1C in human spinal cord and its distribution suggests that it
      plays a role in the control of pain processing.

PMID- 10884051
TI  - Plasma 24S-hydroxycholesterol: a peripheral indicator of neuronal degeneration
      and potential state marker for Alzheimer's disease.
AB  - The conversion of brain cholesterol into 24S-hydroxycholesterol and its
      subsequent release into the periphery is probably an important step for the
      maintenance of brain cholesterol homeostasis. Recent findings suggest that plasma
      24S-hydroxycholesterol may be elevated in Alzheimer's disease (AD) and vascular
      dementia at least at some stage of the disease, suggesting increased brain
      cholesterol turnover during neurodegeneration. We investigated whether plasma 24S
      hydroxycholesterol concentrations depend on the severity of AD and on the
      apolipoprotein E (apoE) genotype. Severity of AD and inheritance of the apoE4
      allele were independently associated with reduced plasma 24S
      hydroxycholesterol/cholesterol ratios. The results suggest that the decrease of
      plasma 24S-hydroxycholesterol/cholesterol in severely affected AD patients is a
      peripheral marker for loss of cholesterol 24S-hydroxylase in the CNS. Inheritance
      of the apoE4 allele may be associated with increased apoE-mediated transport of
      brain cholesterol to the periphery or with decreased activity of the 24S
      hydroxylase. Longitudinal studies will assess the validity of the ratio plasma
      24S-hydroxycholesterol/cholesterol as a state marker for AD.

PMID- 10884053
TI  - Auditory scene analysis in dyslexics.
AB  - It has been argued that dyslexics suffer from temporal sensory processing
      deficits which affect their ability to discriminate speech in quiet environments.
      The impact of auditory deficits on non-language aspects of perception, however,
      is poorly understood. In almost every natural-listening environment, one must
      constantly construct scenes of the auditory world by grouping and analyzing
      sounds generated by multiple sources. We investigated whether dyslexics have
      difficulties grouping sounds. The results demonstrate that dyslexics have an
      impairment in grouping auditory objects that depends both on the sounds'
      frequency and presentation rate (i.e. the spectrotemporal context of the sound).
      We conclude that dyslexics have difficulty constructing scenes of the auditory
      world, and that these deficits can contribute to learning impairments.

PMID- 10884052
TI  - Disruption of feeding behavior in CRH receptor 1-deficient mice is dependent on
      glucocorticoids.
AB  - Corticotropin-releasing hormone (CRH) has been found to markedly suppress food
      intake and reduce body weight. However, it still remains to be clarified whether
      those effects are mediated via either the CRH receptor 1 (CRHR1) or the CRH
      receptor 2 (CRHR2), or both receptor subtypes. Therefore, we investigated whether
      CRHR1-deficient mice (CRHR1-KO) show abnormalities in body weight and feeding
      behavior. CRHR1-KO and wildtype mice showed no difference in the total amount of
      food intake. However, there was a significant disruption in the circadian
      distribution of food intake: CRHR1 mutants consumed significantly more food
      during the light period (p<0.01). The normal diurnal pattern could be completely
      restored by oral administration of corticosterone 21-sulfate (5 mg/l added to the
      water-based liquid diet). We therefore conclude that in CRHR1-KO mice, the
      disruption of feeding behavior might be causally related to glucocorticoid
      deficiency, but that the CRHR1 is not likely to play a critical role in the basal
      regulation of ingestive behavior.

PMID- 10884054
TI  - Neurotoxic effect of high dose methamphetamine administration on the hippocampal
      formation of adult mice: morphometric study using image analyzer.
AB  - The volume of the hippocampal formation was measured after repeated
      methamphetamine (MAP) administration. MAP (30 mg/kg, i.p.) or an equivalent
      volume of saline (SAL) was administered once daily for 5 days to adult male
      BALB/c mice. The animals were perfused 7 days after the last injection, and brain
      sections were stained with cresyl violet and studied with a computer-assisted
      image analyzer. The volume of the molecular layer at the ventral position of the
      dentate gyrus of MAP-treated animals was significantly decreased (77% of control,
      p < 0.001). In contrast, the volumes of the molecular layers at the dorsal and
      midseptal positions of the dentate gyrus did not change after MAP administration.
      Similarly, repeated MAP treatment did not affect the volumes of the granular
      layer and hilus at the dorsal, midseptal or ventral positions of the dentate
      gyrus. The present results are the first to document a persistent neurotoxic
      effect of high dose MAP administration on the hippocampal volume of adult mice.

PMID- 10884055
TI  - Centrally administered orexin/hypocretin activates HPA axis in rats.
AB  - The effects of i.c.v. administration of orexin/hypocretin on plasma ACTH,
      corticosterone and c-fos mRNA in the paraventricular nucleus (PVN) of the rat
      were examined. Plasma ACTH levels were markedly increased at 30 min after i.c.v.
      administration of orexin-A. Plasma corticosterone levels were significantly
      increased in a dose-related manner 30 min after i.c.v. administration of orexin-A
      and orexin-B. In situ hybridization histochemistry revealed that the induction of
      the c-fos mRNA in the parvocellular division of the PVN was increased in a dose
      related manner 30 min after i.c.v. administration of orexin-A and orexin-B. These
      results suggest that central orexin/hypocretin activates hypothalamo-pituitary
      adrenal (HPA) axis and may be involved in stress-induced activation of the HPA
      axis.

PMID- 10884056
TI  - Dendrite extension by methanol extract of Ashwagandha (roots of Withania
      somnifera) in SK-N-SH cells.
AB  - Extension of dendrites and axons in neurons may compensate for and repair damaged
      neuronal circuits in the dementia brain. Our aim in the present study was to
      explore drugs activating neurite outgrowth and regenerating the neuronal network.
      We found that the methanol extract of Ashwagandha (roots of Withania somnifera; 5
      microg/ml) significantly increased the percentage of cells with neurites in human
      neuroblastoma SK-N-SH cells. The effect of the extract was dose- and time
      dependent mRNA levels of the dendritic markers MAP2 and PSD-95 by RT-PCR were
      found to be markedly increased by treatment with the extract, whereas those of
      the axonal marker Tau were not. Immunocytochemistry demonstrated the specific
      expression of MAP2 in neurites extended by the extract. These results suggest
      that the methanol extract of Ashwagandha promotes the formation of dendrites.

PMID- 10884057
TI  - Changes in horizontal oculomotor behaviour coincide with a shift in visual motion
      perception.
AB  - During full-field rotation of the visual field, subjects commonly experience an
      initial perception of object-motion which 'switches' to a perception of self
      motion. We studied the characteristics of the horizontal optokinetic nystagmus
      responses evoked by a moving visual stimulus in these two perceptual states over
      a range of stimulus velocities. During self-motion perception mean eye position
      was found to shift more in the direction of the newly appearing stimulus elements
      with a slight reduction in slow phase gain in comparison to the nystagmus evoked
      during object-motion perception. The results may reflect a modified strategy of
      spatial attention with increased emphasis on anticipatory eye movements during
      visually induced self-motion perception.

PMID- 10884058
TI  - Visualization of neurogenesis in the central nervous system using nestin promoter
      GFP transgenic mice.
AB  - Neurons are generated from neural progenitor cells not only during development
      but also in the mature brain. To develop an in vivo system for analyzing
      neurogenesis, we generated transgenic mice expressing green fluorescent protein
      (GFP) under the control of regulatory regions of the nestin gene. GFP
      fluorescence was observed in areas and during periods connected with
      neurogenesis, including embryonic neuroepithelium, neonatal cerebellum, and
      hippocampal dentate gyrus and rostral migratory pathway from the subventricular
      zone to the olfactory bulb in the adult. GFP-positive cells in the adult brain
      included immature neuronal cells expressing polysialylated NCAM. BrdU labeling
      experiments revealed that newly generated interneurons which migrated rostrally
      from the subventricular zone expressed GFP until they reached the olfactory bulb.
      These results indicate that nestin promoter-GFP transgenic mice can be utilized
      to visualize the regions of neurogenesis throughout the life of the animals and
      to follow the migration and differentiation of newly generated neurons.

PMID- 10884059
TI  - Opposite hemispheric lateralization effects during speaking and singing at motor
      cortex, insula and cerebellum.
AB  - Aside from spoken language, singing represents a second mode of acoustic
      (auditory-vocal) communication in humans. As a new aspect of brain
      lateralization, functional magnetic resonance imaging (fMRI) revealed two
      complementary cerebral networks subserving singing and speaking. Reproduction of
      a non-lyrical tune elicited activation predominantly in the right motor cortex,
      the right anterior insula, and the left cerebellum whereas the opposite response
      pattern emerged during a speech task. In contrast to the hemodynamic responses
      within motor cortex and cerebellum, activation of the intrasylvian cortex turned
      out to be bound to overt task performance. These findings corroborate the
      assumption that the left insula supports the coordination of speech articulation.
      Similarly, the right insula might mediate temporo-spatial control of vocal tract
      musculature during overt singing. Both speech and melody production require the
      integration of sound structure or tonal patterns, respectively, with a speaker's
      emotions and attitudes. Considering the widespread interconnections with premotor
      cortex and limbic structures, the insula is especially suited for this task.

PMID- 10884060
TI  - Adenovirus-mediated gene transfer of basic fibroblast growth factor promotes the
      survival of primary-cultured rat neuronal cells.
AB  - We constructed two replication-deficient recombinant adenovirus vectors coding
      human basic fibroblast growth factor (bFGF), one with and one without the
      interleukin-2 (IL-2) secretory signal sequence and examined their neurotrophic
      effects on primary neuronal cells in vitro. The primary neuronal cells were
      successfully infected at a high efficiency with the adenovirus vectors. bFGF
      protein was detected in the culture medium of the neurons infected with both
      these vectors. The cells infected with the bFGF-expressing adenovirus containing
      the IL-2 signal sequence showed 2- to 10-fold higher levels of secretion levels
      than cells infected with the native bFGF-expressing adenovirus alone. Both bFGF
      expressing vectors augmented the survival of primary neuronal cells in an in
      vitro culture, compared with a mock infection or control virus infection.
      Notably, the cells infected with the bFGF-expressing adenovirus containing the IL
      2 signal sequence were markedly enhanced cell survival in the early phase of the
      culture, compared with the control cells and even those infected with the bFGF
      expressing adenovirus without the IL-2 signal sequence. However, in the late
      phase of neuronal culture, neither viral vector could support the cell survival.
      In contrast the co-infection of the bFGF-expressing vector with a Bcl-xL
      expressing vector was extremely effective on neuronal survival.

PMID- 10884061
TI  - Reciprocal information flow between prefrontal cortex and ventral tegmental area
      in an animal model of schizophrenia.
AB  - The medial prefrontal cortex (PFC) is anatomically and functionally connected
      with the ventral tegmental area (VTA), the neuronal source of mesocorticolimbic
      system that is pathophysiologically related to schizophrenia-like symptoms.
      Methamphetamine (MAP) was applied to examine the functional relationship between
      PFC and VTA in an animal model of schizophrenia. Hyperactivity and stereotyped
      behavior were observed accompanied by a distinctive direction of information
      flow. In hyperactivity, information flow in the direction from PFC to VTA was
      dominant. Contrarily, dominant information flow from VTA to PFC was found in
      stereotyped behavior. These results indicate that dysfunctional interaction
      between PFC and VTA is the neuronal basis of MAP-induced schizophrenia-like
      psychosis. The information flow and its direction can be useful tool to explain
      the neurogenesis of these abnormal behaviors.

PMID- 10884062
TI  - 18-MC reduces methamphetamine and nicotine self-administration in rats.
AB  - In previous studies, 18-methoxycoronaridine (18-MC), a novel iboga alkaloid
      congener, has been found to decrease the intravenous self-administration of
      morphine and cocaine in rats. In the present study, 18-MC (1-40 mg/kg, i.p.) dose
      dependently decreased the i.v. self-administration of methamphetamine and
      nicotine. As in the previous studies, drug self-administration was reduced for >
      or = 24 h after the highest dose of 18-MC. A comparison of 18-MC's interactions
      with all four drugs of abuse studied so far indicated that 18-MC is least
      effective in decreasing methamphetamine self-administration and most potent in
      decreasing nicotine self-administration. The results suggest that a nicotinic
      antagonist action of 18-MC contributes to its putative anti-addictive efficacy.

PMID- 10884063
TI  - Association analysis of the 5-HT5A gene in depression, psychosis and
      antipsychotic response.
AB  - The serotonergic system is targeted by both antidepressants and atypical
      antipsychotic drugs such as clozapine. Genetic variation in the 5-HT5A gene might
      be involved in susceptibility to depression, the major psychoses or in
      influencing clinical response to treatment. To examine this hypothesis we
      genotyped two polymorphisms (-19G/C; 12A/T) in the human 5-HT5A receptor gene in
      a sample of 269 unrelated schizophrenic patients treated with clozapine, 112
      bipolar patients, 75 unipolar patients and 187 controls. After five-fold
      correction for multiple testing, allelic association was found with the -19G/C
      polymorphism and bipolar affective disorder, (p = 0.025; OR 0.56), unipolar
      depression (p = 0.004; OR 0.52) and schizophrenia (p = 0.036; OR 0.67) indicating
      a potential protective effect of the G19 allele. For the 12A/T polymorphism
      allelic association was observed with unipolar depression only (p = 0.004). We
      conclude that allelic variation in the human 5-HT5A receptor gene may be involved
      in susceptibility to schizophrenia and affective disorders but not in determining
      response to clozapine.

PMID- 10884064
TI  - MRI of small human stroke shows reversible diffusion changes in subcortical gray
      matter.
AB  - Six patients who had suffered small cerebral ischemia affecting subcortical gray
      matter were examined with diffusion weighted imaging (DWI) and T2-weighted
      imaging within the first 8 h, during the next 2 days and after 5-16 days. Areas
      of apparent diffusion coefficient (ADC) decreases were observed acutely and
      reached the maximum size during the subsequent 2 days. Noticeably, in all
      subjects, a large portion of the ADC lesion was reversible as judged from the
      lesion size on final T2 image. The regular reversibility of the ADC decreases in
      this setting may indicate a hitherto not understood pathophysiological process
      occurring in small ischemic stroke.

PMID- 10884065
TI  - Cannabinoid-induced working memory impairment is reversed by a second generation
      cholinesterase inhibitor in rats.
AB  - Cannabinoids which impair rat working memory appear to inhibit hippocampal
      extracellular acetylcholine (Ach) release and reduce choline uptake through an
      interaction with CB1 cannabinoid receptors. Here we report that CP 55,940, a
      potent bicyclic synthetic cannabinoid analog, dose-dependently impaired rat
      performance, when given i.p. 20 min before an eight-arm radial maze test. The
      selective CB1 cannabinoid receptor antagonist SR 141716A, given i.p. 20 min
      earlier, significantly reduced the memory deficit Pretreatment with eptastigmine,
      a second generation cholinesterase inhibitor, given orally 100 min before the
      cannabinoid agonist, relieved the memory impairment without affecting CP 55,940
      induced behavioural alterations such as reduced spontaneous motor activity,
      analgesia and hind limb splaying. These data suggest that cannabinoid-induced
      working memory impairment is mediated through a central cholinergic blockade.

PMID- 10884066
TI  - On the search for the vocal pattern generator. A single-unit recording study.
AB  - In the squirrel monkey (Saimiri sciureus), single-unit activity was compared
      between the midbrain periaqueductal grey and the parvocellular and central nuclei
      of the medullary reticular formation during the production of species-specific
      vocalization. It was found that all three areas contain neurones with
      vocalization-related activity. The relative number of specific reactions types
      differed between areas, however. While the majority of periaqueductal cells fired
      just before, but not during vocalization, most cells in the reticular formation
      fired before and during vocalization. Modulation of discharge rate with changing
      fundamental frequency was only found in the reticular formation, not the
      periaqueductal grey. It is concluded that the parvocellular and central nuclei of
      the reticular formation, but not the periaqueductal grey are involved in vocal
      pattern generation.

PMID- 10884067
TI  - Topographic organization of the human primary and secondary somatosensory areas:
      an fMRI study.
AB  - The topographical organization of SI and SII somatosensory areas was investigated
      using fMRI at 1.5 T and electrical sensory stimulation. Electrical stimuli were
      delivered unilaterally to the median nerve at the wrist and to the tibial nerve
      at the medial malleolus, during a block paradigm study. In all subjects,
      activation was observed, contralaterally to the stimulated side, in the post
      central gyrus, in the posterior parietal cortex, in the mesial pre-frontal region
      and, bilaterally, in the supratemporal region at the level of the Sylvian
      fissure. The latter region, corresponding presumably to SII, showed a rough but
      clearcut topographical organization, with the median nerve areas located more
      posteriorly. In addition, weaker activations were observed in some subjects in
      the ipsilateral mesial prefrontal region and in the ipsilateral posterior
      parietal cortex. Information contained in the present study represent an
      interesting database for future investigations on the effects of sensorimotor
      learning in normal individuals on plastic reorganization following a lesion of
      the primary sensorimotor centers, i.e. in stroke patients, on the topography and
      balance between upper and lower limb representations in primary and secondary
      somatosensory cortices.

PMID- 10884068
TI  - Effects of stimulus rate on the auditory cortex using fMRI with 'sparse' temporal
      sampling.
AB  - The purpose of this study was to evaluate the effects of the auditory stimulus
      presentation rate on signal response during fMRI with a minimal effect of scanner
      acoustic noise. Six subjects received auditory stimulus with a pure tone (1000
      Hz, 30 ms duration) at presentation rates of 0.5, 2, 5, 10 and 20 Hz. Echo planar
      images were obtained with a long TR of 12 s and clustered multi-slice
      acquisition. The number of activated pixels and percentage signal change were
      measured in the transverse temporal gyri, which revealed that these values at 5
      Hz were significantly greater than those at 0.5 Hz and at 20 Hz.

PMID- 10884069
TI  - Targeting of tetracycline-regulatable transgene expression specifically to
      neuronal and glial cell populations using adenoviral vectors.
AB  - Targeting regulatable transgene expression specifically to neuronal or glial cell
      populations would facilitate studies of CNS gene function. We have developed the
      tetracycline (Tet) regulatable adenoviral system by expressing the Tet-off
      transactivator (tTA) under the control of the neuronal-specific synapsin I
      promoter and the well characterized glial-specific glial fibrillary acidic
      protein (GFAP) promoter. Transfection of primary hippocampal cultures
      demonstrated that the respective promoters restricted reporter transgene
      expression exclusively to neuronal or glial populations. Delivery of the vectors
      into adult rat hippocampus resulted in a similar pattern of cell specific
      transgene expression. These novel vectors provide a highly effective means of
      directing regulated, cell-specific, transgene expression and as such are
      important tools for investigations of neuronal and glial cell function and
      advancing gene therapy studies.

PMID- 10884070
TI  - Attracting attention to the illusory location of a sound: reflexive crossmodal
      orienting and ventriloquism.
AB  - Sound localization can be affected by vision; in the ventriloquism effect, sounds
      that are hard to localize within hearing become mislocalized toward the location
      of concurrent visual events. Here we tested whether spatial attention is drawn to
      the illusory location of a ventriloquized sound. The study exploited our previous
      finding that visual cues do not attract auditory attention. We report an
      important exception to this rule; auditory attention can be drawn to the location
      of a visual cue when it is paired with a concurrent unlocalizable sound, to
      produce ventriloquism. This demonstrates that crossmodal integration can precede
      reflexive shifts of attention, with such shifts taking place toward the
      crossmodally determined illusory location of a sound. It also shows that
      ventriloquism arises automatically, with objective as well as subjective
      consequences.

PMID- 10884071
TI  - The new voltage gated potassium channel KCNQ5 and neonatal convulsions.
AB  - In 1998, mutations in the voltage gated potassium channel gene KCNQ2 were found
      to be the main cause underlying the autosomal dominant inherited syndrome of
      benign familial neonatal convulsions (BFNC). In one BFNC family a mutation was
      found in an homologous gene, KCNQ3. We have now identified another brain
      expressed member of this ion channel subfamily, KCNQ5, which maps to chromosome
      6q14. On the genomic level KCNQ5 is composed of 14 exons, which are coding for
      897 amino acid residues. Mutation analysis made KCNQ5 unlikely as a candidate
      gene for benign neonatal convulsions in patients with a positive family history
      for neonatal or early infantile seizures, but without mutations in the KCNQ2 or
      KCNQ3 genes.

PMID- 10884072
TI  - The temperatures reached and the damage caused to hair follicles by the normal
      mode ruby laser when used for depilation.
AB  - Although it is proposed that heat is the cause of follicular damage leading to
      depilation, this has never been proved. This study aims to determine the mode by
      which depilation is effected and, if heat is the mechanism, what temperatures are
      reached within treated follicles and if sufficient damage is produced therein.
      Two excised specimens of hair-bearing skin from 5 patients undergoing facelifts
      were dissected to reveal the hair bulbs/shafts on the deep surface. They were
      placed on a jig, and one pulse from a normal-mode ruby laser (NMRL) of 15 J per
      square centimeter was fired on the epidermal surface. A thermal imaging camera
      recorded dermal temperature changes on the deep surface in real time. Specimens
      were then examined histologically for the site and extent of cellular damage by
      immunohistochemical staining for a protein marker of cell damage (p53). The NMRL
      targeted hair follicles specifically. The most common follicular temperature
      increase ranged from 5 to 10 degrees C. In specimens from 1 patient the increase
      was more than 30 degrees C (p < 0.001). Heat dissipation into interfollicular
      tissue in all specimens occurred 2 seconds after exposure. Evidence of laser
      induced damage to follicle-lining cells was found only in those follicles with
      damaged hair shafts. The changes were found to a greater depth (to the bulb) and
      greater extent (beyond the bulge) in those follicles reaching higher
      temperatures. These findings suggest that the NMRL should produce permanent
      depilation. The variability between follicles and between patients explains,
      perhaps, the uneven outcome regarding depilation using the NMRL. Success appears
      to depend on peak follicular temperatures achieved during laser exposure, which
      may result from the follicular characteristics of the individual patient.

PMID- 10884073
TI  - Superior eyelid incision: an alternative approach for frontozygomatic dermoid
      cyst excision.
AB  - Sixty-five children presenting with frontozygomatic (lateral brow) dermoid cysts
      were operated using an upper eyelid crease incision. There were 38 girls and 27
      boys age 3 months to 13 years (mean age, 15 months). The lesions were left sided
      in 32 patients and right sided in 33 patients. Preoperative radiograph or
      computed tomographic scan performed for 25 children failed to demonstrate a bony
      defect in the area of the cyst. At surgery, 14% of the cysts were adherent to the
      periosteum and 5% were subperiosteal. One cyst extended through the bone into the
      orbit. All cysts were removed completely, and this was accomplished without
      rupture in 54 patients. The average operating time was 21 minutes. All children
      were seen within 1 month of surgery. The postoperative course was uneventful
      except for early swelling and erythema in 2 children. Thirty-six patients (55%)
      could be reached for long-term follow-up (range, 1-7.1 years) postoperatively.
      The authors found no lid or ocular dysfunction and excellent scar camouflage in
      all patients.

PMID- 10884074
TI  - Making of a facial perforator map by thermography.
AB  - It has been confirmed that thermography is an effective method by which to locate
      perforators to be used for local flaps. One disadvantage of thermography is its
      complicated procedure. If it was possible to identify perforators quickly and
      easily, many operations would be dramatically simplified. The authors' objective
      was to develop a method of mapping surface perforators using thermography. They
      pressed a vinyl bag filled with ice water against a test area for 25 seconds and
      began photographing the area directly after icing. Almost all of the enhanced hot
      spots appeared for 65 seconds after icing. The number and locations of enhanced
      perforating vessels varied widely, which they anticipated as a result of
      differences among individuals, and fluctuations in the measuring environment and
      the performance of measuring instruments. However, the presence of many
      perforators is common, and these images are considered to be reliable. Based on
      their findings, the authors consider the facial perforator map to be accurate and
      useful. Application of the facial perforator map may simplify many operations and
      may contribute to making surgery safer and more effective.

PMID- 10884075
TI  - Early recovery after endoscopic vs. short-incision open carpal tunnel release.
AB  - Endoscopic carpal tunnel release has been claimed to offer improvement in
      recovery time and postoperative discomfort over open carpal tunnel release. Short
      incision open carpal tunnel release has been claimed to offer recoveries
      comparable with endoscopic techniques. Patients receiving carpal tunnel surgery
      were randomized to short-incision open release or single-portal endoscopic
      release. Preoperative and postoperative evaluation included grip and pinch
      strength measurements and patient completion of a questionnaire regarding
      symptoms and function. Thirty-six operated hands completed evaluation, including
      22 endoscopic and 14 open releases. Early grip and pinch strength after
      endoscopic carpal tunnel release were improved significantly over short-incision
      open release (p < 0.05). Subjective evaluation indicated a trend toward improved
      symptoms and function with endoscopic over short-incision open carpal tunnel
      release. Endoscopic carpal tunnel release provides faster recovery of strength
      than short-incision open carpal tunnel release and improves early postoperative
      comfort and function to a small degree.

PMID- 10884076
TI  - Intra- and interobserver reliability of sensibility testing in asymptomatic
      individuals.
AB  - Threshold and innervation density tests are common clinical tools used in the
      evaluation of peripheral nerve injuries and compression syndromes. The purpose of
      this study is to determine the inter- and intraobserver reliability of Semmes
      Weinstein monofilaments and static and moving two-point discrimination in 48
      volunteers. Kappa coefficients of inter- and intraexaminer agreement were
      generated for each test and investigator. The interexaminer reliability for the
      Semmes-Weinstein monofilaments ranged from fair to moderate in the ulnar and
      median nerve distributions, and slight to moderate in static and moving two-point
      discrimination testing. Intraobserver reliability for Semmes-Weinstein
      monofilaments and static and moving two-point discrimination was slight to fair
      for both examiners. Our data indicate that Semmes-Weinstein monofilaments and two
      point discrimination tests yield unreliable measurements in asymptomatic
      individuals. Although useful in monitoring neurological function in pathological
      states, threshold and innervation density measurements from an unaffected digit
      or extremity may not represent a reliable standard for comparison of abnormal
      values.

PMID- 10884077
TI  - Recovery of sensibility after digital neurorrhaphy: a clinical investigation of
      prognostic factors.
AB  - A multicenter retrospective review of 172 epineural digital nerve repairs using
      microsurgical techniques was performed. A total of 71 men and 25 women ranged in
      age from 5 to 64 years (mean age, 33.3 years). Sharp injuries occurred in 55.6%
      of patients and mild crush occurred in 44.4%. Isolated nerve injuries occurred in
      only 24.6% of patients. The majority of digital nerve injuries involved other
      structures: flexor tendons (33.5%), tendons and fractures (9.0%), and fractures
      (4.2%). Replantations were performed in 18 digits (21.6%) and revascularizations
      in 7 digits (7.2%). Injury to repair was less than 1 day in 47.8%, 2 to 7 days in
      22.6%, 8 to 30 days in 23.3%, and 31 to 300 days in 6.3%. Follow-up averaged 22.2
      months (range, 6-77 months). The authors found a significant correlation between
      age and recovery of sensibility as measured by Weber's two-point discrimination
      test (p < 0.001). Patients older than 40 years demonstrated significantly poorer
      recovery of sensibility than patients younger than 40 years. A trend of better
      sensibility return was noted in the younger age decades (<40) with declining age;
      however, the intergroup differences were not significant. There was also a
      significant correlation between severity of injury and recovery of sensibility (p
      < 0.001). Sharp injuries (8.2 mm) demonstrated significantly improved recovery of
      sensibility compared with mild crush (10.8 mm). Fractures (11.1 mm), fractures
      and tendon involvement (11.4 mm), and replantations (11.8 mm) demonstrated
      significantly diminished recovery of sensibility compared with isolated nerve
      injuries (7.9 mm), tendon involvement (8.1 mm), and revascularizations (9.3 mm).
      There did not appear to be any significant difference in recovery of sensibility
      according to gender, digit involved, radial or ulnar side of digit, median or
      ulnar nerve distribution, level of injury (except for the metacarpophalangeal
      joint and the distal palmar crease where most replantations occurred), or time
      interval from injury to repair. There was a weak negative correlation between
      length of follow-up and recovery of sensation.

PMID- 10884078
TI  - Functional outcome with scaphotrapeziotrapezoid arthrodesis in the treatment of
      Kienbock's disease stage III.
AB  - Scaphotrapeziotrapezoid (STT) arthrodesis for the treatment of Kienbock's disease
      is recommended as a wrist salvage procedure since the publication by Watson and
      colleagues in 1985. Stage IIIa/b of the Lichtman classification is the specific
      indication for this operative-procedure. This study reviews the results of 26
      patients with stage III of Kienbock's disease treated with STT arthrodesis during
      a 6-year period. From 1993 to 1998, 26 patients (16 men, 10 women) were treated
      with STT arthrodesis for Kienbock's disease in stage IIIa/b. The mean follow-up
      was 35 months. Two-rung grip strength was measured by using an electronic
      computerized JAMAR-Dynamometer. Pain was evaluated pre- and postoperatively using
      a visual analog scale. Patients' activities of daily living and general quality
      of life were estimated with the Disabilities of the Arm, Shoulder, and Hand
      (DASH) questionnaire. Also two established wrist scores (Mayo wrist score and
      Krimmer wrist score) including objective and subjective parameters were used.
      Fusion was established in 25 patients after an average period of 7 weeks. Pain
      was reduced substantially to 72% of the preoperative values under resting
      conditions and 60% under stress. Eight patients claimed complete pain relief.
      Grip strength improved to 60% of the opposite side. Active range of motion was
      65% of extension/flexion and 50% of radial/ulnar deviation on average compared
      with the contralateral hand. Twenty of the 26 patients were satisfied with the
      final result and would undergo the operation again. A total of 80% of the
      patients returned to their original occupation. The average DASH score was 24.8,
      the Mayo and Krimmer wrist scores averaged 66 and 67.8 points respectively. The
      procedure combines the advantages of decreasing load to the lunate and
      maintaining carpal height. Pain was markedly reduced, grip strength improved, and
      functional wrist mobility was preserved. The data support increasing confidence
      that STT fusion will stand the test of time.

PMID- 10884079
TI  - Classification of the pattern of intrauterine amputations of the upper limb in
      constriction ring syndrome.
AB  - Twenty patients with congenital upper limb amputations caused by constriction
      rings were reviewed to classify the pattern of these amputations. In the 20
      patients studied, 31 upper limbs had congenital amputations. The pattern of
      amputation was classified into three types. Proximal upper limb amputation was
      considered type I and was only seen in one limb. The most common pattern of
      amputation was digital amputation associated with "coning" or "superimposition"
      of the digits (type II) and was seen in 20 hands. Type II amputations were
      subclassified according to the involvement of all, ulnar, radial, or central
      digits by the constriction ring. In type III amputations (N = 10 limbs), there
      was no associated coning or superimposition of the digits. This type of
      amputation was subclassified into type IIIA (multiple-digit amputations within
      the same hand) and type III B (single-digit amputation). Associated anomalies are
      reviewed and the pathogenesis of constriction rings is discussed.

PMID- 10884080
TI  - Both superficial and deep extremity veins can be used successfully as the
      recipient site for free flaps.
AB  - Many controllable factors can influence free flap success rates, including the
      choice of recipient vessels, which can be as crucial as selecting the optimum
      donor site. The extremities are unique in that their dual venous systems offer an
      even greater diversity of options and perhaps risks. Whether the superficial as
      well as the more conventional deep veins can be used successfully as the
      recipient vein site is an important question analyzed in this retrospective,
      nonrandomized, yet inclusive review of 102 free flaps from the past decade used
      only for extremity defects. During this 10-year period, 144 venous
      microanastomoses, including 41 using superficial recipient veins, were utilized
      for these 102 flaps. There were 10 anastomotic catastrophes (9.8%): half were
      venous in origin and four fifths were salvaged by prompt reexploration. Only one
      venous thrombosis, and that in the deep system, resulted in flap failure. All
      arterial problems in every patient resulted in total flap loss, so that overall
      there was a 94.2% flap success rate. The overall incidence of complications and
      flap failure when the deep vein was the recipient site was 9.6% and 5.5%
      respectively. For superficial veins it was 15.4% and 7.7%, and, if used in a
      combination for dual venous outflow, the incidence was 6.3% for either category.
      There was no significant difference in these rates between groups, and in the
      vast majority of cases either the deep or superficial venous systems could indeed
      be used successfully as the recipient vein for microvascular tissue transfers.

PMID- 10884081
TI  - Microcirculatory window for early detection of allograft rejection.
AB  - The purpose of this study is to introduce a technical detail on a transplantation
      model for in vivo evaluation of microcirculatory changes during the acute phase
      of allograft rejection. The cremaster muscle is incorporated and transplanted
      along with the hind limb to detect and study ischemia/reperfusion injury and the
      acute phase of allograft rejection in rats. Thirty-six animals were studied in
      three experimental groups of 12 animals each. Each group was divided into
      subgroups and microcirculatory measurements were taken at two different time
      periods: 24 and 72 hours. In the ischemic control group (N = 12), cremaster
      muscles were denervated, prepared as a tube flap, and submitted to the same
      interval of ischemia as the other groups but without transplantation. In the
      isograft group (N = 12), rat hind limb-cremaster grafts were transplanted between
      genetically identical Lewis rats (RT11). In the allograft group (N = 12), 12
      transplantations were performed across a major histocompatibility barrier between
      Lewis Brown-Norway (RT-11+/-n) and Lewis (RT 11) rats. The diameters of first-,
      second-, and third-order arterioles and venules; red blood cell velocities; and
      functional capillary density were recorded at 24 and 72 hours after
      transplantation. Daily follow-up observations were continued until 3 days after
      the first clinical signs of graft rejection. The mean number of perfused
      capillaries in the two transplantation groups was significantly lower than in the
      control group at both 24 hours and 72 hours (p < 0.05). Those results were as
      follows: 8.2 +/- 2.1 at 24 hours, 7.7 +/- 0.85 at 72 hours in the ischemic
      control group; 5.4 +/- 0.9 at 24 hours, 6 +/- 0.6 at 72 hours in the isograft
      group; and 5 +/- 0.9 at 24 hours, 5.5 +/- 0.3 at 72 hours in the allograft group.
      Red blood cell velocities and vessel diameters in the main arteries were also
      decreased in transplant groups at 24 hours (p < 0.05) but returned to normal 72
      hours after the operation (p > 0.05). The composite rat hind limb-cremaster model
      presented in this study introduces a reproducible in vivo approach to monitor the
      differences in microcirculatory hemodynamics of ischemia/reperfusion injury and
      acute graft rejection. The model allows the study of the timing, sequence, and
      correlation between clinical and hemodynamic signs during the acute phase of
      allograft rejection.

PMID- 10884082
TI  - Koebner phenomenon: what you don't know may hurt you.
AB  - Koebner phenomenon is the development of isomorphic pathological lesions in
      distant wounds of patients with pre-existing cutaneous diseases. More frequent in
      patients with psoriasis, it can occur in the presence of other cutaneous
      pathologies. Surgeons should be aware of this entity and warn patients about its
      possible occurrence.

PMID- 10884083
TI  - The Koebner phenomenon in immunosuppression-related Kaposi's sarcoma.
AB  - The Koebner phenomenon has been reported to develop in classic or acquired immune
      deficiency syndrome-related Kaposi's sarcoma (KS). A 12-year-old kidney
      transplant recipient who developed immunosuppression-related KS showed
      reoccurrence of lesions in some previously intact incision sites following
      removal of tumor, suggesting Koebner phenomenon. It is recommended that surgeons
      be careful when planning surgical interventions in patients with certain skin
      disorders in which Koebner phenomenon is known to develop.

PMID- 10884084
TI  - How far does an ingrown toenail enlarge?
AB  - Bizarre hypertrophy of the right great toe presented in a 50-year-old woman with
      an ingrown nail, as well as mild hypertrophy of the left great toe. A fingerlike
      overgrowth was thought to be a reactive change resulting from repetitive
      formation of granulation from the histopathological analysis.

PMID- 10884085
TI  - The surgical treatment of Molluscum contagiosum in a pediatric AIDS patient.
AB  - Molluscum contagiosum (MC) has arisen as an opportunistic pathogen in human
      immunodeficiency virus (HIV) disease. Recent reports have focused on the
      presentation of MC in adults who are HIV positive. The authors describe MC in a
      pediatric patient with acquired immmune deficiency syndrome. This particular
      patient showed the same atypical lesion morphology, distribution, and chronic
      course that is seen in the adult HIV patient. As in the adult patient, treatment
      in the pediatric patient also remains challenging, with limited success of
      traditional treatment modalities. The authors were able to achieve long-term
      remission and an excellent cosmetic result through meticulous superficial
      surgical excision of the patient's MC lesions.

PMID- 10884087
TI  - A new technique for the treatment of syndactyly with osseous fusion of the distal
      phalanges.
AB  - In treating complex syndactyly of the hand, including bony union of varying
      degrees, how to cover the exposed bone surface is still disputable. The authors
      adopted a homemade device for the treatment of a case of syndactyly with terminal
      bony union. External tissue expander theory was applied to their device, and
      expansion of the cutaneous bridge was followed by division of the fused distal
      phalanges. Two months later the raw bone could be covered simply with the
      expanded local skin, and no skin graft was needed except for at the base of the
      affected fingers. This technique produces good cosmetic results of the fingertips
      and nail grooves without secondary deformities.

PMID- 10884086
TI  - Endovascular treatment of a pseudoaneurysm of a recipient external carotid artery
      following radiation and free tissue transfer.
AB  - Radical resection and reconstruction after preoperative radiation has become
      routine treatment for patients with certain types and stages of head and neck
      cancers. When microvascular flap reconstruction is required, the recipient
      vessels have been subjected to radiation, making them more thrombogenic and
      friable, thus increasing the risks of postoperative complications. The authors
      report a patient who received preoperative radiation therapy for rhabdomyosarcoma
      of the infratemporal fossa and who underwent a radical resection and free rectus
      musculocutaneous flap reconstruction. The free flap covered the base of the brain
      from the nasopharynx and closed an intraoral defect. The donor artery was
      anastomosed end to side to the external carotid artery stump. The patient
      developed a pseudoaneurysm of the external carotid artery stump 1 month
      postoperatively, which was treated with endovascular coil embolization without
      loss of the flap. Percutaneous transcatheter endovascular treatment of
      pseudoaneurysms that develop after free tissue transfer in head and neck
      reconstruction has not been reported previously. One month after surgery,
      endovascular occlusion of the main arterial supply to the flap did not compromise
      its viability because of collateral revascularization from the peripheral tissue
      bed, despite the patient's history of radiation.

PMID- 10884088
TI  - Aesthetic correction of a contour deformity of the neck with buried expanded
      flaps.
AB  - This case report describes the use of two tissue expanders to correct a contour
      deformity of the neck, secondary to radical block dissection and radiotherapy for
      a recurrent parotid tumor. One flap was deepithelialized and then buried under
      the other to create the necessary bulk. This technique provided tissue similar in
      texture and color to the adjacent skin, and there is minimal donor site
      morbidity. It is, however, a staged procedure.

PMID- 10884089
TI  - A review of the ruby laser with reference to hair depilation.
AB  - There is a clinical need in the fields of reconstructive and cosmetic plastic
      surgery for a safe, simple, and effective method of hair depilation. Depilatory
      clinics have been established throughout the country, commonly using the ruby
      laser, to treat a cohort of the population, estimated to be between 6% and 10%,
      recognized as being hirsute. Clinical trials performed to date have not
      established a protocol that suits the previously mentioned criteria and have
      been, usually, small in number and short in follow-up. With the increased use
      that this form of laser treatment will inevitably undergo, it is the belief of
      the authors that the only way of ascertaining whether the treatment is safe,
      simple, and effective is first to establish how the ruby laser works. This review
      relates the knowledge that is currently available regarding the function of the
      ruby laser to a number of the clinical studies that have been undertaken,
      including three that have used other types of laser. Using this information,
      future areas in which research is required can be defined, ultimately to improve
      the clinical efficacy of ruby laser-assisted hair removal while lessening the
      current side effects (namely, superficial burning, and hypo- and
      hyperpigmentation).

PMID- 10884090
TI  - Green genes.

PMID- 10884091
TI  - Re: microvascular "supercharged" cervical colon: minimizing ischemia in
      esophageal reconstruction.

PMID- 10884092
TI  - Re: a new epineural nerve repair technique: oblique nerve coaptation.

PMID- 10884093
TI  - "Teardrop" implant advisory.

PMID- 10884094
TI  - One-stage sideburn reconstruction with hair-bearing scalp based on the
      retroauricular branch of the superficial temporal vessels.

PMID- 10884095
TI  - Compression neuropathy of the hand after high-pressure air injection.

PMID- 10884096
TI  - Use of a small rubber bandage as a finger tourniquet.

PMID- 10884097
TI  - Distally based fasciocutaneous flaps in reconstruction of heel defects: pitfalls
      revisited.

PMID- 10884098
TI  - Angiolymphoid hyperplasia with eosinophilia of the orbit.

PMID- 10884099
TI  - Glass in the nasoethmoidal, maxillary, and orbital area as a result of windshield
      trauma.

PMID- 10884100
TI  - Aesthetic surgery and Hodgkin's disease.

PMID- 10884101
TI  - Total nasal reconstruction with free and local flaps: controversies and
      difficulties.

PMID- 10884102
TI  - Tiggers and owls.

PMID- 10884103
TI  - Characterization of patients with primary peroneus longus tendinopathy: a review
      of twenty-two cases.
AB  - Between 1985 and 1996 we treated 22 patients with a diagnosis of PLT which was
      confirmed by MRI and/or surgery. This review identifies the shared clinical
      traits and associated pathology of our patients. Clinically, 82% of the patients
      had a cavo-varus hindfoot position. This finding was supported by measurements of
      the calcaneal pitch angle and the calcaneal-lst metatarsal angle which both
      showed the patients in this study to be in the 90th percentile for the general
      population for arch height. The combined MRI and surgical findings revealed
      injury to the peroneus longus at the cuboid notch in 17 of 22 cases. The subgroup
      of surgical findings demonstrated that all 6 complete tears occurred at the
      cuboid notch, while 8 of 9 (89%) of the partial tears involved the region of the
      lateral calcaneal process. In addition, the surgical findings showed 7 of the
      cases (33%) to have associated peroneus brevis tendon involvement, with an
      increased incidence when the longus pathology occurred at the cuboid notch. The
      findings predicated by MRI correlated well with the surgical findings, but there
      was a tendency for MRI to predict a more severe level of pathology. A grading
      system developed to compare the MRI and surgical findings is presented. This
      study facilitates making the diagnosis of PLT by drawing attention to the common
      characteristic of the cavo-varus foot position and the common locations of tendon
      injury.

PMID- 10884104
TI  - Augmented repair of acute Achilles tendon ruptures.
AB  - Twenty-five patients who had an acute Achilles tendon rupture were managed with
      an augmented repair using the gastrocnemius-soleus fascia. All patients healed
      their repair and there were no re-ruptures. There was one infection. Augmented
      repair allowed early functional recovery as evidenced by full ankle motion by
      four to eight weeks, full unassisted weight bearing by three weeks, cessation of
      braces by four weeks, and return to work by one to six weeks post-operatively.
      Augmentation adds a sufficient amount of collagen to allow early range of motion
      and weight bearing without re-rupture. Disadvantages included a long incision,
      soft tissue prominence, one infection, and sural nerve injury.

PMID- 10884105
TI  - Anatomy of the sural nerve and its relation to the Achilles tendon.
AB  - Sural nerve injury is a complication of Achilles Tendon (TA) rupture. We
      dissected 30 cadaveric lower limbs to describe the course of the sural nerve in
      relation to the TA. At the level of insertion of the TA into the calcaneum, the
      sural nerve was a mean 18.8 mm from the lateral border of the TA. The proximal
      course of the nerve was towards the midline such that it crossed the lateral
      border of the TA at a mean distance of 9.8 cm from the calcaneum. The significant
      individual variation in the position of the sural nerve in relation to the
      achilles tendon should be borne in mind when placing sutures in the proximal part
      of the achilles tendon. Percutaneous sutures should not be placed in the lateral
      half of the TA.

PMID- 10884106
TI  - The Viladot implant in flatfooted children.
AB  - In 1991, Viladot described an implant for the treatment of painless flatfeet in
      children. This was inserted through a double approach to allow the talus to
      function while limiting its ability to slide off the calcaneus. The wineglass
      shaped prosthesis was inserted into the sinus tarsi with a tibialis posterior
      advancement and soft tissue correction to allow the foot to adopt a neutral
      position. This is in keeping with other procedures described for the correction
      of flatfoot. Viladot reported excellent results in 234 feet operated on in such a
      manner using clinical, radiological and photopodographic parameters. In
      Sheffield, over three years, 22 implants were inserted for similar painless
      flatfeet in children. The results were assessed using clinical, radiological and
      pedobarographic parameters. Viladot was able to demonstrate an improvement in all
      cases, clinically, radiologically and photopodographically with little or no
      discomfort and a return to preoperative levels of activity including sport. We
      found that in all cases, postoperative pain was a major feature which limited
      activity in all but 2 feet and which reduced the ability to take part in sport
      and other preoperative pastimes. Unlike Viladot, we were unable to demonstrate
      consistent improvements radiologically. Pedobarographically, the loading of the
      first metatarsal head remained unchanged and the centre of pressure was corrected
      in only 14%.

PMID- 10884107
TI  - Talo-navicular arthrodesis for residual midfoot deformities of a previously
      corrected clubfoot.
AB  - Triangular navicular, dorsal-lateral subluxation of the talo-navicular (TN) joint
      with a secondary forefoot cavovarus deformity, and degenerative changes of the TN
      joint are frequent causes of residual clubfoot deformity and pain in the midfoot
      after surgical correction. This study investigates the usefulness of TN
      arthrodesis to correct these deformities and to resolve symptoms resulting from
      these deformities. During the period from 1991-1996, the senior author performed
      19 TN fusions (16 patients) for the above residual clubfoot deformities involving
      a painful TN joint. Eight of the procedures (seven patients) also required a
      lateral column shortening with a calcaneal wedge osteotomy to allow for a
      complete correction of the TN joint. The procedure was only performed in cases
      involving a hindfoot that was adequately aligned during a previous clubfoot
      correction. The average age of the patients at the time of surgery was 11 years
      (range: 4-20). One patient (bilateral procedures) was lost to follow-up. Fifteen
      patients (17 procedures) were followed-up for an average of four years (range: 2
      6). All patients reported symptomatic improvement after the TN arthrodesis.
      Fourteen of the patients (15 procedures) were completely satisfied. The remaining
      patient (bilateral procedures) was only partially satisfied due to the subsequent
      development of navicular-cuneiform osteoarthritis in both feet. Two cases (2
      patients) developed complications requiring a second procedure for satisfactory
      results. In addition, the procedure resulted in an improvement of the talus-first
      metatarsal angle on both antero-posterior and lateral radiographs. TN arthrodesis
      produced a correction of the residual clubfoot deformities of the midfoot and
      resulted in satisfactory clinical improvement in all the patients.

PMID- 10884108
TI  - Influence of the interosseous talocalcaneal ligament injury on stability of the
      ankle-subtalar joint complex--a cadaveric experimental study.
AB  - The present study aims to clarify the influence of the interosseous talocalcaneal
      ligament (ITCL) injury associated with injury to the lateral ankle ligaments on
      the ankle-subtalar joint complex motion under conditions of physiologic loading.
      We conducted mechanical tests using five fresh cadaveric lower extremities. Each
      specimen was mounted in the loading device and an axial cyclic load from 9.8 to
      686 N was applied. Three-dimensional rotations of the ankle and the subtalar
      joint were measured simultaneously by a linkage electric goniometer. Mechanical
      tests were repeated after sectioning of the anterior talofibular ligament (ATFL),
      and again after additional sectioning of the ITCL. In the intact condition, the
      ankle and the subtalar joints rotated consistently with increase of the load. The
      predominant rotations were plantar flexion and adduction at the ankle joint, with
      some eversion demonstrated at the subtalar joint. Although ATFL sectioning did
      not significantly change the motion of the two joints, additional sectioning of
      the ITCL significantly increased adduction and total rotation of the ankle joint.
      The present study demonstrated that a combined injury of the ATFL and the ITCL
      can induce anterolateral rotatory instability of the ankle joint under conditions
      of axial loading.

PMID- 10884109
TI  - Peripheral nerve vein wrapping for intractable lower extremity pain.
AB  - HYPOTHESIS/PURPOSE: The purpose of this study was to determine the effectiveness
      of lower extremity peripheral nerve vein wrapping procedures in the management of
      patients with intractable lower extremity pain. The hypothesis was that nerve
      insulation through vein wrapping is effective in treating symptoms related to
      adhesive neuralgia, but not those secondary to intraneural damage. METHODS: We
      retrospectively reviewed 25 consecutive patients whose intractable chronic lower
      extremity peripheral neuralgia had been treated with revision neurolysis and vein
      wrapping. The 14 women and 11 men had an average age of 39 years (range, 21 to 53
      years). Vein wrapping was performed using a saphenous vein autograft in 19
      patients and a fetal umbilical vein in six patients. The average length of follow
      up after vein wrapping was 24 months (range, 12 to 63 months). Assessment of pain
      and dysfunction was on a scale of 0 (no pain/dysfunction) to 10 (severe enough to
      prompt request for amputation and required use of a wheelchair). RESULTS: Pain
      scores improved from a preoperative average of 8.7 points (range, 6 to 10 points)
      to a postoperative average of 4.6 points (range, 0 to 10 points); dysfunction
      improved from a preoperative average of 7.3 points (range, 3 to 10 points) to a
      postoperative average of 4.4 points (range, 0 to 9 points). Although 17/25
      patients were satisfied with the procedure, only 14/25 stated they would undergo
      the surgery again. All eight patients who exhibited no improvement had
      preoperative and intraoperative evidence of an idiopathic etiology and/or
      intraneural damage. Preoperatively, 18/25 patients could not work;
      postoperatively, that number improved to 8/25. CONCLUSIONS: Vein wrapping of
      lower extremity peripheral nerves is most effective in relieving symptoms related
      to adhesive neuralgia and less beneficial in the presence of intraneural damage.
      Although symptoms are rarely relieved completely, vein wrapping typically results
      in a substantial improvement in symptoms related to scar entrapment of peripheral
      nerves.

PMID- 10884110
TI  - Sensory thresholds of normal human feet.
AB  - HYPOTHESES/PURPOSE: Although several studies in the literature have evaluated the
      abnormal sensory thresholds of diabetic feet to Semmes-Weinstein monofilament
      testing, there is very limited data on the sensory thresholds of individuals
      without diabetes or peripheral neuropathy. The purpose of this study was to
      assess the dorsal and plantar sensation of the feet from 40 healthy, college-aged
      volunteers using Semmes-Weinstein monofilaments. CONCLUSIONS/SIGNIFICANCE: Semmes
      Weinstein testing is a useful tool in predicting which diabetic patients may be
      at risk for ulceration of the feet. Several studies have determined 5.07 to be
      the threshold for protective sensation. Based on the normal values derived in
      this study, the inability to feel a Semmes-Weinstein monofilament of 5.07 (as in
      diabetic neuropathy) represents a sensory threshold that is more than 50 times
      greater than normal. This means that roughly 98% of the sensory ability has been
      lost. METHODS: 20 male and 20 female volunteers between the ages of 18 to 22
      years old were selected. None had a history of any significant injury or previous
      surgery to the foot or ankle. There were no known medical conditions associated
      with decreased foot sensation, (e.g.- diabetes, syphilis, leprosy,
      myelomeningocele, syringomyelia, or hereditary neuropathy). Volunteers were also
      questioned regarding participation in athletic activities. The subjects were
      blindfolded with the leg resting comfortably on a chair as 14 plantar and 5
      dorsal locations were tested on each foot. The right foot was always tested
      first. Each site on the foot had the Semmes-Weinstein monofilaments applied to it
      first, in an order of increasing stiffness, then repeated in decreasing order,
      using all twenty monofilaments in the set. A positive threshold response was
      recorded when the subject could feel the filament and could accurately locate
      where on the foot the stimulus had been applied. The left foot was then tested in
      an identical fashion. RESULTS: The mean sensitivity for all sites was 3.63
      (0.0075 SEM). There were significant differences between sites, between using
      increasing or decreasing monofilament stiffness, between subjects, and in some
      instances, between right foot and left foot values. When testing was performed
      from the higher to lower monofilament stiffness, subjects were found to have
      significantly better sensitivity, which indicates the importance of a consistent
      testing protocol (either all up or all down). Sensation in the lesser toes and
      the arch were the most sensitive followed by the hallux and the plantar
      metatarsal heads. The least sensitive site was the heel, with 1/6th the
      sensitivity of the most sensitive toes.

PMID- 10884111
TI  - Endoscopic plantar fasciotomy for chronic heel pain.
AB  - The purpose of our study was to determine whether endoscopic plantar fasciotomy
      is a safe and effective operation in this patient population. We reviewed our
      surgical results following endoscopic plantar fasciotomy in sixteen patients
      (twenty feet) with an average preoperative duration of symptoms of four years. Of
      the 20 feet, 9 had complete relief of pain while symptoms were improved in nine
      feet. One patient with bilateral symptoms had no relief in either foot. The
      average AOFAS hindfoot score improved from 62 to 80, a statistically significant
      difference. Unilateral patients did better than bilateral with no bilateral
      patients reporting complete resolution of symptoms. There were no iatrogenic
      nerve injuries. On the basis of our review, we recommend endoscopic plantar
      fasciotomy as an alternative to open plantar fascial release for those patients
      with recalcitrant heel pain.

PMID- 10884112
TI  - Endoscopic release of plantar fasciitis--a benign procedure?
AB  - This is a case report of a patient suffering from subcalcaneal pain syndrome due
      to plantar fasciitis that was resistant to non surgical treatment. After
      endoscopic partial release of the plantar fascia the patient was pain free for
      several weeks, before he became symptomatic again. This new pain was located more
      proximally. An MRI study showed a stress reaction of the calcaneus.

PMID- 10884113
TI  - The MR imaging appearance of longitudinal split tears of the peroneus brevis
      tendon.
AB  - PURPOSE: Longitudinal split tears of the peroneus brevis tendon have been
      increasingly reported as a source of lateral ankle pain and disability. MR
      imaging is useful in identifying the appearance of longitudinal split tears of
      the peroneus brevis tendon to differentiate this entity from other causes of
      chronic lateral ankle pain. We observed variations in anatomy associated with
      these tears. MATERIALS AND METHODS: Twenty-two patients (eleven males, eleven
      females) were identified as having longitudinal split tears of the peroneus
      brevis tendon. These cases were reviewed retrospectively to evaluate for the
      following: shape of the peroneus brevis tendon, high signal in the peroneus
      brevis tendon, tendon subluxation, appearance of the superior peroneal
      retinaculum, presence of osseous changes in the ankle, lateral ankle ligaments,
      presence of a bony fibular spur, flattening of the peroneal groove of the fibula
      and presence of a peroneus quartus. A control group consisted of twenty ankles
      imaged for reasons other than lateral ankle pain. The same structures were
      assessed in this group. A Fisher's exact P-value was used to determine the
      significance of each finding in the two groups. RESULTS: Statistically
      significant associated findings were chevron shaped tendon (p = .0001), high
      signal in the peroneus brevis (p = .0017), bony changes (p = .0001), flat
      peroneal groove (p = .0001), abnormal lateral ligaments (p = .0004), and lateral
      fibular spur (p = .0006). CONCLUSIONS: MR imaging is useful in differentiating
      longitudinal split tears of the peroneus brevis tendon from other lateral ankle
      disorders. It can show the extent of the abnormality in the tendon and the
      associated findings of soft tissue and/or bone variations which must be addressed
      at the time of surgery.

PMID- 10884114
TI  - Open reduction and internal fixation of a simultaneous lesser metatarsal fracture
      and MPJ dislocation.

PMID- 10884115
TI  - Extending the indications for distal chevron osteotomy.
AB  - Distal chevron osteotomy is a widely employed procedure for correction of mild to
      moderate hallux valgus. The author has modified the angle of the osteotomy to
      provide even greater stability and allow larger displacements of the distal
      fragment. This modification allows the correction of a greater degree of hallux
      valgus than originally described for the technique. This modification is
      relatively simple and increases the stability compared to the original
      publication.

PMID- 10884116
TI  - Survey of necropsy results in captive red wolves (Canis rufus), 1992-1996.
AB  - Through the Red Wolf Species Survival Plan, the captive red wolf (Canis rufus)
      population was developed with the intent of reestablishing wild populations. One
      part of the plan was a survey for diseases that might occur as a result of
      population homogeneity or that might impede breeding success and reintroduction.
      For this survey, complete necropsies and histopathologic analyses were performed
      on 62 red wolves from 1992 to 1996. Major causes of 22 neonatal deaths were
      parental trauma, parasitic pneumonia, and septicemia. Common neonatal lesions
      included pododermatitis and systemic ascariasis. Cardiovascular anomalies and
      systemic parasitism were found in two juveniles. Causes of death in the 38 adults
      included conspecific trauma, neoplasia, or gastrointestinal diseases such as
      necrotizing enteritis, intestinal perforation, and gastric volvulus.
      Lymphosarcoma represented 50% of the fatal neoplasms. Three adults died from
      cardiovascular failure or hyperthermia during handling, and several adults were
      euthanized for suspected genetic diseases. Overall, the captive population had
      few significant health problems, but population fitness might be improved by
      continued removal of potentially deleterious genes from the breeding population
      and by modifying the husbandry of neonates and adults.

PMID- 10884117
TI  - Field anesthesia of free-living mountain gorillas (Gorilla gorilla beringei) from
      the Virunga Volcano region, Central Africa.
AB  - Twenty-six anesthetic procedures involving 24 free-living mountain gorillas
      (Gorilla gorilla beringei) from Rwanda or the Democratic Republic of Congo were
      performed between February 1987 and October 1997. Sixteen procedures were
      performed to remove snares or to treat snare-related wounds, and four of the
      animals died without recovering consciousness because of their severe medical
      conditions. Ketamine was used for induction 19 times, tiletamine/zolazepam was
      used five times, and the agent was not recorded for two procedures. The mean (+/-
      SD) ketamine dosage for four animals of known weight was 7.1 +/- 0.9 mg/kg. All
      induction agents were delivered i.m. by remote injection, and mean induction
      times for ketamine and tiletamine/zolazepam were 5.5 +/- 2.6 min (n = 12) and 5.4
      +/- 3.7 min (n = 5), respectively. Mean recovery times were significantly shorter
      with ketamine compared with tiletamine/zolazepam (42.0 +/- 24.9 min, n = 9 vs.
      75.25 +/- 22.1 min, n = 4). Low hemoglobin oxygen saturation (mean = 86.7%) was
      recorded in three cases under ketamine anesthesia, and oxygen insufflation is
      therefore recommended to prevent hypoxemia. Gorillas induced with
      tiletamine/zolazepam had significantly higher respiratory rates compared with
      animals given ketamine. Successful anesthesia and recovery, in particular,
      depended on the assistance of local personnel.

PMID- 10884118
TI  - Degenerative spinal disease in large felids.
AB  - Degenerative spinal disorders, including intervertebral disc disease and
      spondylosis, seldom occur in domestic cats. In contrast, a retrospective study of
      13 lions (Panthera leo), 16 tigers (Panthera tigris), 4 leopards (Panthera
      pardis), 1 snow leopard (Panthera uncia), and 3 jaguars (Panthera onca) from the
      Knoxville Zoo that died or were euthanatized from 1976 to 1996 indicated that
      degenerative spinal disease is an important problem in large nondomestic felids.
      The medical record, radiographic data, and the necropsy report of each animal
      were examined for evidence of intervertebral disc disease or spondylosis. Eight
      (three lions, four tigers, and one leopard) animals were diagnosed with
      degenerative spinal disease. Clinical signs included progressively decreased
      activity, moderate to severe rear limb muscle atrophy, chronic intermittent rear
      limb paresis, and ataxia. The age at onset of clinical signs was 10-19 yr (median
      = 18 yr). Radiographic evaluation of the spinal column was useful in assessing
      the severity of spinal lesions, and results were correlated with necropsy
      findings. Lesions were frequently multifocal, included intervertebral disc
      mineralization or herniation with collapsed intervertebral disc spaces, and were
      most common in the lumbar area but also involved cervical and thoracic vertebrae.
      Marked spondylosis was present in the cats with intervertebral disc disease,
      presumably subsequent to vertebral instability. Six of the animals' spinal cords
      were examined histologically, and five had acute or chronic damage to the spinal
      cord secondary to disc protrusion. Spinal disease should be suspected in
      geriatric large felids with decreased appetite or activity. Radiographic
      evaluation of the spinal column is the most useful method to assess the type and
      severity of spinal lesions.

PMID- 10884119
TI  - Proliferative osteoarthritis and osteoarthrosis in 15 snakes.
AB  - Fifteen snakes representing seven species with segmental, proliferative
      osteoarthritis and osteoarthrosis of the spine were presented for examination.
      All the snakes were captive, privately owned, and fed domestic rodents. Physical
      examination, radiography, blood culture, bone culture, necropsy, and
      histopathology were performed on each snake. All the snakes had similar physical
      examination, radiologic, and necropsy findings. There were three histologic types
      of lesions: active bacterial osteoarthritis, predominantly noninflammatory
      osteoarthrosis with multifocal inflammation suggestive of chronic bacterial
      osteoarthritis, and noninflammatory lesions consistent with osteoarthrosis
      without evidence of inflammation or bacteria. These findings suggest that all
      these snakes represent a single disease process, bacterial infection of the
      vertebrae. The different histologic lesions observed in these snakes may be a
      continuum of lesions, from acute to chronic. Gram-negative bacteria were isolated
      from the blood or bone lesions of 8 of the 15 snakes. In six of these eight
      snakes, Salmonella species were isolated. Gram-positive bacteria (Streptococcus
      sp.) were isolated from two other snakes. Blood and bone culture results were
      well correlated, so blood culture may be effective for detecting active bacterial
      osteoarthritis.

PMID- 10884120
TI  - Sedative and cardiopulmonary effects of medetomidine and reversal with
      atipamezole in desert tortoises (Gopherus agassizii).
AB  - Ten desert tortoises (Gopherus agassizii) were given i.m. injections of 150
      microg/kg of medetomidine. Sedation was achieved in all tortoises by 20 min
      postinjection and was accompanied by a significant decrease in mean heart and
      respiratory rates, systolic, diastolic, and mean ventricular pressures, and mean
      ventricular partial pressure of oxygen (PO2). There was no change in mean blood
      pH, HCO3, Na+, K+, ionized calcium values, and mean ventricular partial pressure
      of carbon dioxide (PCO2). There were statistically significant but clinically
      insignificant changes in mean base excess and pH-corrected ionized calcium
      values. Atipamezole given to five of the tortoises at 0.75 mg/kg i.m.
      significantly reversed the sedative effects of the medetomidine, with all
      tortoises returning to a normal state by 30 min after administration of the
      reversal agent. In comparison, the other five tortoises given an equal volume of
      physiologic saline in place of atipamezole (control group) remained significantly
      sedated for the duration of the study. In addition, the heart rate and
      ventricular PO2 returned to baseline, but the respiratory rate and ventricular
      blood pressures were not significantly altered by the atipamezole as compared
      with those of the control group. These cardiopulmonary and physiologic effects
      are similar to those seen in some domestic mammals. Medetomidine can be used to
      safely induce sedation in desert tortoises. For procedures lasting greater than
      120 min, supplemental oxygen should be provided. Atipamezole will reverse the
      sedation but not all of the cardiopulmonary effects, thus necessitating continued
      monitoring after reversal. Future studies should address the anesthetic and
      cardiopulmonary effects of medetomidine in combination with other agents such as
      ketamine and/or butorphanol.

PMID- 10884122
TI  - Serum oxytetracycline concentrations in African elephant (Loxodonta africana)
      calves after long-acting formulation injection.
AB  - Serum oxytetracycline pharmacokinetics were studied in 18 African elephant
      (Loxodonta africana) calves. Each elephant received separate injections of
      oxytetracycline at approximately 18 mg/kg i.m. and 8 mg/kg i.v. in a cross-over
      study. Blood samples were drawn at 0, 24, 48, 72, and 96 hr postinjection. An
      additional sample was drawn 110 hr before the animals were reinjected in the
      cross-over study and a final blood sample was drawn 48 hr after the second dose.
      No lameness or stiffness was observed following i.m. injections. Serum
      oxytetracycline concentrations >0.5 microg/ml were present 48 hr after initial
      dosing for all elephants (i.m., i.v., high or low dosage). Only elephants given
      the high i.m. dosage (18 mg/kg) maintained levels >0.5 microg/ml 72 hr
      postinjection. No significant difference in serum oxytetracycline concentration
      with time was observed between the groups given different i.v. dosages. These
      studies demonstrated that quantifiable serum oxytetracycline concentrations can
      be maintained in young African elephants with a low-dosage multidose i.m.
      regimen.

PMID- 10884121
TI  - Health evaluation of arctic fox (Alopex lagopus) cubs in Sweden.
AB  - Hematologic, serum biochemistry, and serum cortisol reference ranges were
      established and tonsil/rectal bacterial and fecal parasite examinations were
      performed on 21 wild arctic fox (Alopex lagopus) cubs during July 1996. Several
      of the hematologic and serum biochemistry values fell within normal ranges for
      other wild canids or domestic dogs of the same age class. Serum alanine
      transaminase and creatine phosphokinase values were significantly higher in the
      youngest cubs. Proteus vulgaris and Escherichia coli were isolated from both
      tonsilar and rectal swabs of several cubs in all dens. The most common
      gastrointestinal parasite ova were Toxascaris leonina (59%), Isospora spp. (52%),
      Uncinaria stenocephala (33%), and Capillaria spp. (26%). Prevalence of T. leonina
      differed significantly between dens and between age groups. Hematologic and serum
      biochemistry values and degree of parasitism may be indicators of health, stress,
      and nutritional status of arctic foxes.

PMID- 10884123
TI  - Pharmacokinetics of piperacillan after intramuscular injection in red-tailed
      hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus).
AB  - This study characterized and compared the pharmacokinetics of piperacillin after
      single 100 mg/kg i.m. injections in nine red-tailed hawks (Buteo jamaicensis) and
      five great horned owls (Bubo virginianus) over 48 hr by a modified agar well
      diffusion microbial inhibition assay. The mean maximum plasma piperacillin
      concentrations were 204 microg/ml and 221 microg/ml for the hawks and owls,
      respectively, and times of maximum concentrations were 15 min and 30 min,
      respectively. The calculated mean terminal elimination half-lives were 77 min in
      the hawks and 118 min in the owls. Area-under-the-curve values were 218 +/- 52
      microg x hr/ml in the hawks and 444 +/- 104 microg x hr/ml in the owls. On the
      basis of the most common minimal inhibitory concentration (90%) for various
      bacterial isolates from clinical samples of 8 microg/ml, analysis of the data
      suggests that the maximum dosing interval for piperacillin at 100 mg/kg in medium
      sized raptors should be 4-6 hr.

PMID- 10884124
TI  - Surgical implantation of radiotelemetry transmitters in European badgers (Meles
      meles).
AB  - The suitabilities of two subcutaneous and two intraabdominal surgical approaches
      were evaluated for implantation of telemetry transmitters in the European badger
      (Meles meles). Two transmitters, one for heart rate and the other for body
      temperature, were needed in each badger. Five wild badgers were trapped, housed
      in an outdoor pen, anesthetized, and surgically implanted with one or two
      transmitters per procedure. A total of 16 transmitters were implanted, 10
      subcutaneously and six intraabdominally, and each badger had up to three
      procedures performed. Six subcutaneous transmitters were placed over the chest
      wall and four on the dorsal aspect of the neck. Three intraabdominal transmitters
      were placed free in the abdomen and three were fixed to the abdominal wall. Eight
      of the subcutaneous transmitters were later damaged or dislodged, probably by
      mechanical friction, injuries from fighting, or wound licking. The intraabdominal
      implantation procedures were easier and faster to perform compared with
      subcutaneous procedures. Two of the free intraabdominal transmitters became
      thinly encapsulated, with some omental adhesions. The fixed intraabdominal
      approach for transmitter implantation is preferable in badgers.

PMID- 10884125
TI  - Parasites and parasite stages of free-ranging wild lions (Panthera leo) of
      northern Tanzania.
AB  - Fecal samples from 33 lions (Panthera leo) in Serengeti National Park and
      Ngorongoro Crater Conservation Area in northern Tanzania contained 19 different
      parasites, 12 of which, including Aelurostrongylus sp., a species of
      Acanthocephala, a species of Anoplocephalidae, Capillaria sp., Demodex sp.,
      Eimeria sp., Habronema sp., Isospora felis, Isospora rivolta, one species of
      Isospora that was previously undescribed from lions, one species of Trematoda
      that was previously undescribed from lions, and Trichuris sp., were new reports
      for lions. Seven other species had been previously reported from lions.

PMID- 10884126
TI  - Medetomidine/tiletamine/zolazepam and xylazine/tiletamine/zolazepam combinations
      for immobilization of fallow deer (Cervus dama).
AB  - Eleven adult fallow deer (Cervus dama) were anesthetized using a mixture of
      xylazine/tiletamine/zolazepam, and 10 were anesthetized with a mixture of
      medetomidine/tiletamine/zolazepam. Anesthesia was adequate for capture in all
      instances, and minor surgical procedures were possible in seven of the animals
      treated with xylazine/tiletamine/zolazepam and in all of the animals treated with
      medetomidine/tiletamine/zolazepam. Blood gas, hematologic, serum biochemical, and
      cardiorespiratory parameters were measured during all immobilizations. The deer
      immobilized with xylazine/tiletamine/zolazepam had significantly higher lactate
      and cortisol values than the deer immobilized with the medetomidine combination.
      Although both methods were adequate for fallow deer, the
      medetomidine/tiletamine/zolazepam combination produced superior results.

PMID- 10884127
TI  - Cerebral infarction and myocardial fibrosis in a white-handed gibbon (Hylobates
      lar).
AB  - A white-handed gibbon (Hylobates lar) lost the use of its right hand. Complete
      blood count, serum chemistry profile, electrocardiographic findings, blood
      pressure, and radiographic work-up were normal, but the gibbon died 2 days later.
      The gibbon was serologically positive for herpes simplex I and Epstein-Barr
      virus. Necropsy and histopathology showed acute infarction of the right cerebrum
      and multifocal to coalescing severe myocardial fibrosis.

PMID- 10884128
TI  - Acute lymphoblastic leukemia in a juvenile southern black rhinoceros (Diceros
      bicornis minor).
AB  - A 21-mo-old female southern black rhinoceros (Diceros bicornis minor) developed
      acute upper respiratory dyspnea in association with lymphadenopathy and marked
      immature lymphocytosis. A diagnosis of acute lymphoblastic leukemia was reached
      on the basis of the morphologic and cytochemical characteristics of peripheral
      lymphoblasts. Antineoplastic chemotherapy included administration of cytarabine,
      cyclophosphamide, vincristine, and doxorubicin, with clinical remission achieved
      19 days after initiation of treatment. The rhinoceros died, however, of
      congestive heart failure, presumably secondary to doxorubicin cardiotoxicity and
      a particular sensitivity of rhinoceros myocardial tissue to free hydroxyl
      radicals. The pharmacologic effects of any therapeutic agent need to be carefully
      considered before use in the black rhinoceros, especially within the context of
      the unique physiology of this species.

PMID- 10884129
TI  - Halicephalobus gingivalis (Nematoda) infection in a Grevy's zebra (Equus grevyi).
AB  - A 6-yr-old female Grevy's zebra (Equus grevyi) with a disseminated rhabditiform
      nematode infection is described. Antemortem clinical signs were limited to
      blindness and abnormal behavior believed to be caused by a recurrent nematode
      induced uveitis. Histologic examination of the kidneys, heart, eyes, uterus, and
      lymph nodes revealed granulomas containing multiple sections of rhabditiform
      nematodes. Most of the recovered nematodes were larval stages with only a few
      adult females noted. The adults measured 243-297 microm x 11-16 microm (x = 269 x
      14 microm). The distinctive rhabditiform esophagi had corpus:isthmus:bulb
      proportions of 19:11:5. On the basis of adult morphology, the nematode was
      identified as Halicephalobus gingivalis. This is the first report of this
      parasite in a zebra and indicates that this parasitic granulomatous disease
      should be considered in zebras with neurologic disease.

PMID- 10884130
TI  - Detection of Sarcocystis neurona in the brain of a Grant's zebra (Equus burchelli
      bohmi).
AB  - An 8-yr-old intact male Grant's zebra (Equus burchelli bohmi) was referred to the
      Veterinary Medical Teaching Hospital of the University of California-Davis after
      being found in the owner's pasture obtunded and in lateral recumbency. The animal
      was hypothermic, weak, and unwilling to rise. There was no evidence of trauma,
      and the zebra had seemed normal the preceding evening. There was no extensor
      rigidity, and cranial nerve reflexes were normal. Flexor and extensor reflexes
      were weak upon initial examination. A complete blood count and serum biochemistry
      analysis revealed a mild leukocytosis, hyperfibrinogenemia, hypoglycemia,
      hyponatremia, hypochloremia, hypocalcemia, and hypoalbuminemia. Urinalysis was
      normal, and a urine toxicology screen for alkaloids was negative. No toxic
      substance was found in the hay or pasture grasses although the owner reported the
      presence of yellow star thistle and mushrooms in the pasture. The cerebrospinal
      fluid cytologic and biochemical analyses were normal, but antibodies to
      Sarcocystis neurona were detected. The zebra died despite aggressive supportive
      therapy over a 4-day period. The necropsy demonstrated severe gastrointestinal
      nematodiasis that could account for hypoalbuminemia and electrolyte
      abnormalities. Histopathologic examination of the nervous system revealed focal
      areas of perivascular cuffing in the brainstem that were comprised mainly of
      lymphocytes, monocytes, and plasma cells. Immunohistochemical staining identified
      the presence of S. neurona merozoites associated with the lesions. This zebra
      probably died from severe endoparasitism that resulted in malabsorption,
      weakness, and recumbency rather than from encephalitis associated with S. neurona
      merozoites. Equine protozoal myeloencephalitis has not been reported previously
      in nondomestic equids.

PMID- 10884131
TI  - Malignant melanoma in a Eurasian otter (Lutra lutra).
AB  - An 11-yr-old female Eurasian otter (Lutra lutra) presented with multiple
      cutaneous nodules identified histologically as malignant melanomas of spindle
      cell and epithelioid cell type. Metastases were detected in lymph nodes and
      liver, and the tumor, which was derived from melanocytes, showed aggressive
      biological behavior. Only occasional reports exist of neoplastic disease in
      otters.

PMID- 10884132
TI  - Pentastomiasis in Bosc's monitor lizards (Varanus exanthematicus) caused by an
      undescribed Sambonia species.
AB  - Two wild-caught Bosc's monitor lizards (Varanus exanthematicus) developed
      clinical signs of pentasomiasis approximately 3 yr after arrival in the United
      Kingdom. One died of chronic parasitic pneumonia associated with adult
      pentastomids of an undescribed Sambonia species. Eggs and immature pentastomids
      were also seen in histologic sections of the lungs and liver. The other animal
      was treated for pneumonia and for nodular inflammation of the larynx that
      restricted the diameter of the glottis. Fragments of pentastomid larvae were seen
      in a laryngeal biopsy, and the animal recovered after treatment with ivermectin
      and supportive therapy.

PMID- 10884133
TI  - Cestodiasis with intestinal diverticulosis in a lesser flamingo (Phoeniconaias
      minor).
AB  - An adult female lesser flamingo (Phoeniconaias minor), caught in the African Rift
      Valley in 1991 and subsequently housed at the Baltimore Zoo, died of severe
      visceral gout in 1996. Necropsy revealed a white, moderately firm, nodular
      lesion, 1 cm in diameter, in the serosal wall of the small intestine. Although it
      was initially thought to be a tumor or focal granuloma, histologic examination
      revealed multiple cestodes deeply embedded at the base of the crypts between the
      intestinal villi, with their massive scolices (up to 3.4 mm in diameter)
      distending these spaces into multiple diverticulae. The mucosal epithelium
      surrounding the scolices was severely attenuated. Around the diverticulae, in the
      submucosa and muscularis, was a mild to moderate lymphocytic reaction and mild
      fibrosis. The proximity of multiple scolices and extensive invasion of host
      tissue suggested that the infection occupied a preexisting lesion. The cestodes
      were cyclophyllids but were distinct from any species previously reported from
      flamingos. Helminths should be included in differential diagnoses for
      gastrointestinal nodules in flamingos.

PMID- 10884134
TI  - An undescribed Demodex sp. and demodicosis in a captive koala (Phascolarctos
      cinereus).
AB  - A 12-yr-old male koala (Phascolarctos cinereus) in a zoo collection developed
      bilateral, noninflammatory, periocular alopecia. Deep periocular skin scrapings
      yielded multiple adult, nymphal, and larval mites of a previously undescribed
      Demodex species. Skin biopsies from affected areas revealed multiple mites in
      superficial keratin and within hair follicles, associated with a mild intramural
      lymphocytic folliculitis. Treatment with daily oral ivermectin was safe and
      effective. Although Demodex sp. are previously reported from skin scrapings in
      another koala with periocular alopecia, this is the first confirmed case of koala
      demodicosis.

PMID- 10884135
TI  - Thoracic vertebral chordoma in a domestic ferret (Mustela putorius furo).
AB  - A castrated adult male 1.0-kg domestic ferret (Mustela putorius furo) was
      referred for evaluation of a mass of >5 mo duration that was associated with the
      thoracic spine. The ferret had motor dysfunction and no conscious proprioception
      or pain perception in either hind limb. Segmental reflexes were present. Survey
      radiography, myelography, and magnetic resonance imaging showed a mass involving
      the ninth and 10 thoracic vertebrae and compressing the spinal cord.
      Decompressive surgery was performed, but clinical signs persisted. A diagnosis of
      chordoma was made using histopathology and immunohistochemistry. This is the
      first reported case of a chordoma involving the thoracic vertebrae in a domestic
      ferret.

PMID- 10884136
TI  - Melting corneal ulcer management in a greater one-horned rhinoceros (Rhinoceros
      unicornis).
AB  - Acute unilateral keratomalacia, probably secondary to trauma, occurred in a
      greater one-horned rhinoceros (Rhinoceros unicornis) transferred between zoologic
      facilities. Following 2 days of medical treatment, a 360 degrees conjunctival
      surgical graft was performed. Staphylococcus and yeast were isolated from a
      perioperative culture of the affected eye and were treated with antimicrobials.
      There was rapid healing and minimal midcorneal scar formation with peripheral
      corneal clarity.

PMID- 10884137
TI  - Facilitation of Asian elephant (Elephas maximus) standing immobilization and
      anesthesia with a sling.
AB  - An Asian elephant (Elephas maximus) required general anesthesia for orthopedic
      foot surgery. The elephant was unable to lie down, so it was placed in a custom
      made sling, administered i.m. etorphine hydrochloride in the standing position,
      and lowered to lateral recumbency. General anesthesia was maintained with
      isoflurane administered through an endotracheal tube. After surgery, the
      isoflurane anesthesia was terminated, with immobilization maintained with
      additional i.v. etorphine. The elephant was lifted to the vertical position, and
      the immobilizing effects of etorphine were reversed with naltrexone. The
      suspension system and hoist for the sling were designed specifically for the
      elephant house.

PMID- 10884138
TI  - Cuterebra myiasis in a group of red kangaroos (Megaleia rufa), a Bennett's
      wallaby (Macropus rufogriseus fruticus), and a Gunther's dik dik (Maloqua
      guentheri smithi).
AB  - A group of four red kangaroos (Megaleia rufa), a Bennett's wallaby (Macropus
      rufogriseus fruticus), and a Gunther's dik dik (Maloqua guentheri smithi) were
      presented over a 2-mo period with draining lesions over the thorax or on the
      lateral aspect of a hind leg. Only one animal exhibited more than one lesion.
      Physical examinations revealed infections with fly larvae. The parasites were
      manually removed and identified as Cuterebra spp. All of the affected animals
      survived, with no apparent side effects.

PMID- 10884139
TI  - Clinical challenge. Acute necrotizing enteritis with microabscesses due to
      Yersinia pseudotuberculosis.

PMID- 10884140
TI  - Clinical challenge. Acute prolapse of the rectum.

PMID- 10884141
TI  - Towards a new millennium.

PMID- 10884142
TI  - Research challenges arising from changes in worklife.
AB  - Great challenges for occupational health research are set by the rapid changes in
      the world of work as a consequence of globalization, new technologies,
      demographic workforce changes, fragmentation of enterprises and work contracts,
      high time pressures, high demands for learning new skills, and growing worker
      mobility. The occupational health problems are of 2 types, the persistent and
      reemerging old problems of occupational injuries and diseases and new challenges
      from psychological stress, musculoskeletal disorders caused by computerized work,
      cognitive ergonomics in information-intensive work, the work ability of aging
      workers, and new trends in occupational allergies. The 3 roles of research,
      improvement of knowledge, improvement of understanding, and support of the
      development of work conditions in practice, all call for new initiatives in
      occupational health research. The new comprehensive strategy for the development
      and promotion of work ability has been found to respond effectively to these new
      needs.

PMID- 10884143
TI  - Etiologic research: needed revisions of concepts and principles.
AB  - Even though etiologic research has been the central concern in academic
      epidemiology, its concepts have remained confused or malformed, starting from
      that of etiology itself; and the same applies to its principles, starting from
      the notion that the principal variants of an etiologic study are the 'cohort'
      study and the 'case-control' study. This article suggests revisions of some
      central concepts pertaining to the object (and objective) of an etiologic study,
      and it posits an updated conception of the essence--singular--the study itself.
      This is supplemented by some novel, yet merely orientational, propositions in
      respect to quality-assurance in etiologic research.

PMID- 10884144
TI  - Occupational cancer epidemiology in the coming decades.
AB  - Occupational studies have identified many of the established chemical
      carcinogens. Studies in the next millennium will be needed to identify the
      hazardous agents in occupations known to have high cancer rates, to assess human
      risks from animal carcinogens that have not been well evaluated
      epidemiologically, to provide information on women and minorities, to evaluate
      interactions with genetic factors and other risk factors, to contribute to our
      understanding of risks from the spread of chemicals from the workplace to the
      general environment, and to identify mechanisms of cancer. The traditional
      retrospective cohort design will be insufficient to meet these needs. Population
      based case-control, nested case-control, prospective cohorts, and cross-sectional
      designs will assume more important roles because of the need to collect
      information on nonoccupational risk factors and biological tissues. Improvement
      in the assessment of quantitative exposures is needed for the efficient
      evaluation of interactions between occupational exposures, genetic factors, and
      nonoccupational exposures.

PMID- 10884145
TI  - Promise of molecular epidemiology--epidemiologic reasoning, biological rationale
      and risk assessment.
AB  - Molecular epidemiology has emerged as a natural outgrowth of attempts to apply
      information derived from the explosion in molecular biology to disease in human
      populations. The incorporation of biomarkers into classical epidemiologic designs
      holds the promise of unraveling mechanisms, elucidating gene-environment
      interactions, and dissecting heterogeneity. The primary interest of molecular
      epidemiology is in the identification of factors in the physical and social
      environment which affect the risk for disease and which are amenable to
      preventive intervention. The explosion in molecular technology has not, however,
      resulted in radical, widespread improvements in epidemiologic results and
      therefore has led to a sense of frustration in the public health community. As
      experience accumulates, there is new appreciation that attention to study design,
      infrastructure, and biomarker validation can improve the results.

PMID- 10884146
TI  - Challenges to retrospective exposure assessment.
AB  - Retrospective exposure assessment has become a crucial component in the
      interpretation of occupational epidemiologic results. Many advances have been
      made over the last 2 decades, but substantial progress is still necessary to
      reduce the misclassification of exposure. The efforts needed include evaluating
      the validity and reliability of assessment methods, better documentation of the
      methods, use of exposure determinants to estimate exposure levels more accurately
      and reliably, and an increase in the understanding of industrial hygiene and
      biological measurement data and questionnaires, their limitations, and how to use
      them best. In addition, better characterization of exposures is necessary. This
      need includes evaluating dermal and ingestion hazards, incorporating
      nonoccupational sources of exposures, particularly hobbies, evaluating the effect
      of multiple chemicals, and exploring different exposure metrics.

PMID- 10884147
TI  - Dermal route in systemic exposure.
AB  - To evaluate risk from dermal exposure, the amount of material on the skin must
      first be measured. The potential for dermal uptake must then be assessed for the
      potential health effects from systemic exposure. No standard methods exist for
      studying these processes, and published data are not comparable because of the
      different techniques used. Future validated methodology should provide a sound
      scientific basis for risk assessment. Methods for measuring skin and surface
      contamination will require development of reference contaminated surfaces and
      skin as part of quality control procedures. Biological monitoring is a valuable
      tool in the assessment of dermal absorption, in contributing to the validation of
      in vitro techniques, and in risk assessment and management. It will be necessary
      to conduct detailed investigations to support risk assessment for dermal
      exposure. Ultimately, predictive models will be established for exposure and for
      dermal absorption to support a generic approach and allow risk assessment
      strategies appropriate to actual workplace situations.

PMID- 10884148
TI  - Biomarkers and their use in occupational medicine.
AB  - Biomarkers of exposure, parent chemicals, metabolites, and also hemoglobin and
      DNA (deoxyribonucleic acid) adducts, even urinary mutagenicity, have been used
      successfully to identify exposed persons, follow-up exposure, and quantitatively
      assess exposure. Some have been validated as indicators of health risk. The
      avenues for future biomarkers of exposure are in the development of robust,
      simple, and inexpensive semiquantitative methods for daily use on every worker
      for assuring that no (excessive) exposure takes place. Some biomarkers of effect
      have also been well validated and are widely used in routine monitoring
      activities. However, with the exception of cholinesterase inhibitors, biomarkers
      of effect offer little advantage over the analysis of the chemical itself. Their
      use will be limited to carefully planned ad hoc studies. Biomarkers of
      susceptibility currently have no practical application in worker health
      protection. Biomarker research should concentrate on validating methods, in terms
      of the prediction of health effects, and on elucidating exposure-biomarker
      concentration relationships.

PMID- 10884149
TI  - Environmental fertility research at the turn of the century.
AB  - Research into environmental causes of impaired human fertility is still immature.
      Knowledge on the strengths and limitations of several research options, the main
      sources of bias, the occurrence of infertility and subfecundity in several
      countries, the patterns of contraceptive behavior, and the distribution of sperm
      counts at the population level has advanced, but the much-debated questions about
      temporal and regional trends in fertility and semen quality remain unsettled.
      Refined biological markers of male fecundity and markers feasible for large-scale
      studies of female fecundity are needed. The effects of several life-style factors
      have been characterized successfully, but the detrimental effects of
      environmental exposures have not. Most studies are either inconclusive or fail to
      demonstrate any important risks. If comprehensive knowledge on biological
      mechanisms is a criterion of maturity, epidemiologic and toxicologic fertility
      research is young. The new millennium will be challenged to determine the role
      played by the environment in developed countries, wrong exposure time windows,
      too crude or inappropriate measures of fertility, and overlooked critical
      exposures.

PMID- 10884150
TI  - Progress and potential of genetic susceptibility to environmental toxicants.
AB  - Gene-environment interactions are thought to be critical for such multifactorial
      diseases as cancer, diabetes, heart disease, asthma, and some neurological
      disorders. The genetic constitution of an individual (genotype) may influence the
      risk of disease of a person exposed to environmental or occupational insults.
      Major advances will occur in the coming years with respect to the identification
      of the genetic and molecular causes of susceptibility to common diseases. In
      these studies microarrays and chip technology are rapidly becoming central in the
      detection of mutations and polymorphisms and in functional genomics. These rapid
      advances in genetics present new and complex ethical issues for both the
      individual and society.

PMID- 10884151
TI  - Parental exposure, adverse pregnancy and offspring effects--perspectives in
      developmental epidemiology.
AB  - Developmental health is governed by biology and the societal culture that shapes
      family planning. This context should not be ignored in epidemiologic studies that
      address the effect of parental exposure from environmental and occupational
      agents on prenatal development, growth and survival, on adverse birth effects, or
      on postnatal events. It is important to have a thorough basic knowledge of
      developmental health in the population under study and to consider this basis in
      study design and performance. One way of accomplishing this task is to combine
      strengths of population-based cohort studies and nested case-control studies.
      Sibship-based cohorts and case-control studies that make use of biomarkers may
      provide particular advantages. Future research on the impact of parental exposure
      should be more strongly based on biological knowledge about the genetic, immune,
      and endocrine regulation of prenatal growth and development.

PMID- 10884152
TI  - Challenges for research and prevention in relation to work and cardiovascular
      diseases.
AB  - The purpose of this paper is to discuss future challenges for research and
      prevention in the field of work environment and cardiovascular diseases (CVD).
      First, research on CVD and work during the last half of the 20th century is
      discussed. Second, the theories dominating the last 20 years are presented.
      Third, cardiovascular and occupational epidemiology are compared, and it is
      stressed that occupational epidemiology should avoid the individualistic bias of
      mainstream cardiovascular epidemiology. Finally, future challenges are discussed,
      and improvements are recommended concerning the use of intermediate end points,
      intervention research, theories about chemical and physical risk factors, the use
      of a unifying model for society, stress, and health, and the application of
      integrated prevention. It is concluded that research on CVD and work can play an
      important part in the development of integrated prevention strategies for the
      next century.

PMID- 10884153
TI  - Challenges for the new century in the epidemiology of adult asthma.
AB  - Numerous risk factors are associated with asthma. To achieve adequate precision
      in epidemiologic studies of asthma, large populations and specific diagnostic
      methods are to be preferred. The association between air pollution (in a wide
      sense) and adult-onset asthma is well-known, but little is known about the actual
      risks. In published studies the fraction of adult-onset asthma caused by
      occupational exposures ranges from 4.8% to 36%. Whether subjects with preexisting
      asthma are at an increased risk for impairment due to asthma when they are
      exposed to irritants is an issue of great relevance. The literature addressing
      these problems is scant. The challenge facing us is to design epidemiologic
      studies on adult asthma that lead to answers to the following questions: (i) has
      the incidence of asthma increased among adults, (ii) to what extent is adult
      onset asthma caused by occupational exposure, (iii) does preexisting asthma get
      worse due to exposures in the workplace?

PMID- 10884154
TI  - New avenues in research on musculoskeletal disorders.
AB  - Recent reviews on musculoskeletal disorders have clearly pointed out the need for
      more good-quality original research. Both symptom-based and objective outcome
      assessment methods should be improved. A variety of methods exists to assess
      exposure for short-term outcomes, whereas exposure assessment strategies for
      outcomes with long induction times should be developed. The change in exposure
      patterns--less force demands, more static, visual, cognitive, psychological and
      social load--will continue during the next millennium, and a likely result is a
      change in the disease panorama. The pathomechanisms of the effects of low-level
      static contractions and adverse psychosocial conditions need clarification.
      Genetic epidemiology is an emerging field of research, and it will be
      particularly interesting to study the interaction between genetically determined
      susceptibility and occupational risk factors. Because degeneration of the spine
      starts in adolescence, the importance of studying the etiology of degenerative
      disorders among young populations is emphasized.

PMID- 10884155
TI  - Model development and research vision for the future of multiple chemical
      sensitivity.
AB  - Multiple chemical sensitivity (MCS) is characterized by heightened self-reported
      sensitivity to extremely low concentrations of chemicals. It has numerous
      symptoms in common with the sick building syndrome, the Gulf War syndrome, and
      chronic fatigue. Despite much research, reproducible objective findings are
      lacking for MCS, as is a sound model to explain it. This paper proposes a 2-step
      model combining the needed epidemiologic terminology with that of
      psychophysiological activation and sensitization. It is suggested that different
      environmental stressors act as initiators. After initiation, the limbic system
      and other parts of the brain become sensitized and hyperreactive to environmental
      triggers. Odor acts as one important trigger. Future research should use more
      biological assessments in combination with environmental and psychosocial data
      and involve patient groups with similar symptoms, although diagnosed as suffering
      from different entities. The similarities and differences of patients with such
      entities need to be understood before the entities themselves can be understood,
      diagnosed, treated, and prevented.

PMID- 10884156
TI  - Challenges for indoor environment research in the new office.
AB  - This paper discusses new directions for indoor environment research for the
      following 4 themes: (i) the current change in office work pattern, workplace
      design, and increasing demands from the work force, (ii) the large individual
      variation in requirements for optimal conditions pointing at the key factors of
      individual response and individual control options based on trade-off
      experiments, (iii) psychosocial factors as determinants of symptoms, comfort, and
      productivity, and (iv) transient, nonspecific symptoms in the indoor environment,
      the identification of causes, and long-term consequences.

PMID- 10884157
TI  - Future prevention and handling of environmental accidents.
AB  - According to the 1995 World Disaster Report, accidents are second only to floods
      in frequency. Chemical accidents leading to a serious danger to the general
      public and to the environment rank 10th, just after epidemics and followed by
      landslides. Can the occurrence of these environmental accidents be reduced in the
      future and their consequences minimized? The answer is yes, provided that
      decisions are made and actions implemented now. Future management of
      environmental accidents requires that the same effort so far devoted to relief
      measures in the postimpact phase be devoted to advance planning in the
      preaccident period. International cooperation should be activated to predispose
      risk reduction measures, including a hazard-oriented approach to prevention,
      preparedness plans for possible incidents in major hazardous installations, and
      collaborative programs and resource sharing for response to accidents and the
      follow-up of their consequences. Clear and unequivocal communication with the
      public, with other professionals, decision makers, and the media play a key role
      in each step.

PMID- 10884158
TI  - Organizational interventions: facing the limits of the natural science paradigm.
AB  - This paper reviews current challenges in the conceptualization, design, and
      evaluation of organizational interventions to improve occupational health. It
      argues that attempts to confirm cause-and-effect relationships and allow
      prediction (maximize internal validity) are often made at the expense of
      generalizability (external validity). The current, dominant experimental paradigm
      in the occupational health research establishment, with its emphasis on
      identifying causal connections, focuses attention on outcome at the expense of
      process. Interventions should be examined in terms of (i) conceptualization,
      design and implementation (macroprocesses) and (ii) the theoretical mediating
      mechanisms involved (microprocesses). These processes are likely to be more
      generalizable than outcomes. Their examination may require the use of both
      qualitative and quantitative methodologies. It is suggested that such an approach
      holds unexplored promise for the healthier design, management, and organization
      of future work.

PMID- 10884159
TI  - Influence of worklife on public health.
AB  - The paper discusses worklife changes with broad public health impacts. Central
      concepts for the analysis of the labor market are flexibility and
      differentiation. One conclusion is that there is ongoing polarization and
      differentiation--with an increased group of people in time-restricted
      (contingent) employment and self-employment and a reduced group of core workers.
      Greater demands for adaptability are being imposed on the majority of employees.
      Concepts related to flexibility and differentiation at an individual level are
      adaptability, identity formation, loss of control, trust and lack of trust,
      allostatic load, long-term strain, and psychological contracting. The labor
      market and organizational changes are discussed in relation to what can be called
      "institutional effectiveness". These changes refer to how institutions
      commissioned to act for the prevention of injuries and to contribute to worklife
      quality handle the new conditions. Finally, work-environment research is
      discussed in relation to a new and more complex pattern of exposures and
      interactions. One conclusion drawn is that it is becoming increasingly difficult
      to identify workplaces at risk.

PMID- 10884160
TI  - Knowledge jobs--how to manage without burnout?
AB  - The working world is progressing from the industrial era to the era of knowledge.
      The critical factor of success in work is shifting from machines to the human
      mind. All work that essentially uses and produces knowledge during and as a
      result of the work process can be defined as knowledge work. Knowledge jobs
      involve many health-promoting features, but stress and burnout may be caused by
      the rapid increase in the knowledge-intensity of work, new job demands, and
      emerging new professional subcultures emphasizing excessive commitment to work.
      Very little empirical evidence is available on these developments. Much more
      research is needed to understand the essential features of knowledge work, the
      change in organizational cultures, and the values guiding this process from the
      point of view of human resources. Research is also needed to develop
      organizational strategies for the prevention of stress and burnout in knowledge
      jobs.

PMID- 10884161
TI  - Towards the 24-hour society--new approaches for aging shift workers?
AB  - The new "24-hour society" increases night work and the diversity of flexible work
      hour patterns. At the same time, the number of older shift workers is growing in
      most developed countries due to the general aging of the working population.
      Together with new experimental and epidemiologic data on the alarming
      relationship of shift work to fatigue, performance, accidents, and chronic health
      effects like coronary heart disease, there is reason to believe that shift work
      may become a major occupational health and safety problem in the near future. The
      prevention of shiftwork-related health and safety problems will be a major
      challenge for the employer, employees, and occupational health professionals
      during the next few decades. The present paper shortly summarizes the current
      knowledge on the relationship between shift work, aging, and health and outlines
      practical countermeasures and research needs to improve the health and well-being
      of aging shift workers.

PMID- 10884162
TI  - How to deal with stress in organizations?--a health perspective on theory and
      practice.
AB  - This review is focused on organizational aspects of stress reduction. Theoretical
      models are presented. The association with a few health outcomes (cardiovascular
      disease, musculoskeletal disorders, and functional gastrointestinal illness) is
      examined. A few examples of evaluations of health consequences of improved work
      organization are introduced. Realistic expectations are discussed against the
      background of etiologic fractions. Concepts like psychological demands, decision
      latitude, social support, and effort-reward balance or imbalance are discussed
      and related to practical reorganizational efforts.

PMID- 10884163
TI  - Challenges facing occupational health services in the 21st century.
AB  - The mission and tasks of occupational health services are reviewed in the context
      of the global megatrends of productivity increase, population overgrowth, and the
      implications of changes in the technology of information and communication.
      Current trends in attempts to achieve harmonization with respect to the concept
      and tasks of occupational health services in the European Union are described,
      along with the basic features of occupational health services as a human service
      organization with implications for the setting of objectives and criteria for
      assessing quality and performance and ethics. The need to adopt a quality-focused
      approach to occupational health service programs is emphasized, and some of the
      inhibitions and obstacles to quality work are mentioned. The need for
      professional commitment to develop and implement quality concepts is outlined.
      Evidence-based health care in the setting of occupational health services and
      some salient aspects of professional ethics in the 21st century are commented on.

PMID- 10884164
TI  - Call for an international ban on asbestos.

PMID- 10884165
TI  - Effects of simulated pulmonary surfactant on the cytotoxicity and DNA-damaging
      activity of respirable quartz and kaolin.
AB  - Respirable-sized quartz and kaolin dusts were pretreated with simulated pulmonary
      surfactant dispersions of dipalmitoyl phosphatidylcholine (DPPC) in saline to
      model the conditioning of particles depositing in alveolar regions of the lung.
      DPPC-treated and untreated dusts were used to challenge lavaged rat pulmonary
      alveolar macrophages in vitro. Cytotoxicity was determined over a 5-d period
      using both total and viable cell counts from a fluorescence-based viability
      assay. DNA damage, as an indication of genotoxicity, was determined over a 7-d
      period by the single-cell gel electrophoresis assay. Untreated quartz and kaolin
      both expressed a significant and potent cytotoxicity, which increased with
      concentration and time. DPPC-surfactant pretreatment delayed significant
      expression of this cytotoxicity until 3 to 5 d after challenge. Untreated quartz
      also caused DNA damage, which increased with concentration and time. DPPC
      surfactant treatment of quartz delayed most DNA damage expression to 5 and 7 d.
      Untreated kaolin expressed weaker activity for DNA damage, significant at the
      highest concentration through 5 d, and at the higher concentrations on d 7.
      Surfactant treatment delayed most kaolin activity for DNA damage to 7 d after
      challenge.

PMID- 10884166
TI  - Toxicity evaluation of petroleum blending streams: reproductive and developmental
      effects of light catalytic reformed naphtha distillate in rats.
AB  - A distillate of light catalytic reformed naphtha (CAS number 64741-63-5, LCRN-D)
      administered by inhalation was tested for reproductive and developmental toxicity
      in Sprague-Dawley rats, following a modified OECD Guideline 421,
      Reproductive/Developmental Toxicity Screening protocol. LCRN-D was administered
      as a vapor, 6 h/d, 7 d/wk at target concentrations of 0, 750, 2500 or 7500 ppm to
      female rats for approximately 6 wk from 2 wk prior to mating, during mating
      through gestational d 19, and to males beginning 2 wk prior to mating for
      approximately 7 consecutive weeks. Dams and litters were sacrificed on postnatal
      d 4 and males were sacrificed within the week after the last litter was
      necropsied. Parental systemic effects observed at the 7500 ppm exposure level
      included slightly lower body weights for males throughout the study. Increased
      kidney to body weight and increased liver to body weight ratio in male rats
      exposed to 7500 ppm LCRN-D may be related to slightly lower final mean body
      weights. Body and organ weight data for female rats in all exposure groups were
      comparable to controls. No test-material-related microscopic changes were
      observed in the reproductive organs or nasal turbinate tissue of either sex.
      Reproductive performance was unaffected by exposure to LCRN-D. The mating and
      fertility indices were 100% in all groups. There were no significant exposure
      related differences in implantation sites or live pups per litter, and no gross
      abnormalities were observed in pups from treated dams. Pups born from LCRN-D
      exposed dams showed comparable body weights and weight gain to control pups. The
      viability index on postpartum d 4 was > or =97%. Under conditions of this study,
      the no-observed-adverse-effect level (NOAEL) for exposure to light catalytic
      reformed naphtha distillate for parental effects was 2500 ppm and the NOAEL for
      reproductive and developmental toxicity was 7500 ppm.

PMID- 10884167
TI  - Neonatal estrogen treatment and its consequences for thymus development, serum
      level of autoantibodies to cardiolipin, and the delayed-type hypersensitivity
      response.
AB  - Eight-week-old female and male NMRI mice treated neonatally with the synthetic
      estrogen diethylstilbestrol (DES), estradiol-17beta, or tamoxifen displayed an
      enlarged thymus when compared with controls (approximately 1.5-fold). In control
      females, either ovariectomy or adrenalectomy increased thymus weight to the level
      characteristic for DES-treated females, but these endocrine ablations had no
      significant effect in DES females. The serum estrogen levels were similar in
      intact DES, ovariectomized DES, and ovariectomized female controls; serum
      corticosterone was similar in controls and DES females. The expression of the
      Thy1.2+ marker and the percentages of CD4+CD8+ DP and CD4+ and CD8+ SP cell
      subsets were similar in thymocyte populations from 8-wk-old controls and DES
      females; the CD4+ and CD8+ SP subsets were similar in splenocyte populations. The
      levels of serum immunoglobulin (Ig) G and IgM autoantibodies to cardiolipin
      showed age-dependent fluctuations but were similar in controls and DES females;
      however, the IgG autoantibodies in DES females were qualitatively different from
      those in controls with respect to sensitivity to bovine serum (a source of beta2
      glycoprotein I). Contrary to females, DES-treated males had higher levels of
      autoantibodies than controls. The delayed-type hypersensitivity (DTH) response to
      oxazolone was similar in controls and DES animals at 8 wk, increased in DES
      females and males at 6 mo, but was reduced in DES females at 1 yr. Thus, even
      though adult mice with thymus enlargement after neonatal estrogen treatment do
      not differ from controls with respect to the expression of the Thy1.2 marker or
      percentages of CD4+/CD8+ DP or SP subsets in thymus and spleen, qualitative and
      quantitative differences occur in immune parameters (autoantibodies to
      cardiolipin) and a T-cell-dependent immune response (DTH).

PMID- 10884168
TI  - Humic acid-induced echinocyte transformation in human erythrocytes:
      characterization of morphological changes and determination of the mechanism
      underlying damage.
AB  - Blackfoot disease (BFD) is a peripheral arterial occlusive disease found among
      human inhabitants along the southwest coast of Taiwan. Well water used for
      drinking and cooking contains humic acid (HA), which may be a possible
      etiological factor. In this study, HA toxicity was investigated in human
      erythrocytes and was found to induce echinocytic formation. Morphological changes
      occurred in both a concentration- and time-dependent fashion. The presence of HA
      was also observed to facilitate the loading of erythrocytes with excess Ca(2+) (1
      mM), which may have occurred following permeability changes in cell membranes,
      leading to echinocytic transformations. Sodium dodecyl sulfate (SDS) gel
      electrophoresis indicated that echinocyte formation was due to the oxidation of
      normal membrane proteins that were replaced by high-molecular-weight proteins.
      Humic acid also induced hemoglobin oxidation in erythrocytes. Data show that
      oxidative stress generated by HA as well as direct effects were exerted on the
      cytoskeleton of erythrocytes, and these may be significant factors in the
      etiology of BFD.

PMID- 10884169
TI  - Facial reanimation with jump interpositional graft hypoglossal facial anastomosis
      and hypoglossal facial anastomosis: evolution in management of facial paralysis.
AB  - When viable proximal facial nerve is inacessible, facial nerve paralysis has been
      classically managed with the hypoglossal facial anastomosis (HFA) for at least
      the past 70 years. While this procedure has proven its reliability, its problems
      with hemilingual atrophy (speech deglutition, drooling, mastication), hypertonia,
      synkinesis, and mimetic deficits indicate the need for a more perfect solution
      for facial paralysis. The jump interpositional graft hypoglossal facial
      anastomosis (JIGHFA) along with gold weight lid implantation and
      electromyographic (EMG) rehabilitation achieves substantial facial reanimation
      without hemilingual deficits. We present our results in 18 patients who underwent
      JIGHFA along with gold weight lid implantation and EMG rehabilitation for facial
      paralysis. These results were compared with those from published series of 30
      patients treated with HFA with EMG rehabilitation evaluated with objective (House
      Brackmann) criteria. Anonymous retrospective information from questionnaires from
      22 of 48 patients who were treated with the classic HFA was also presented. In
      properly selected patients, the JIGHFA technique is capable of achieving
      substantial facial reinnervation (House-Brackmann grade III or better) in 83.3%
      of the patients without hemilingual sequelae which was seen in 45% of the HFA
      patients. In contrast to the HFA, this procedure can be used by patients with
      concomitant lower cranial nerve paralysis (except hypoglossal), and bilateral
      facial paralysis. Hypertonia, synkinesis, and lagophthalmus were less symptomatic
      in the JIGHFA patients. Mimetic expression was not improved in the JIGHFA
      population compared with the HFA group.

PMID- 10884170
TI  - Distance education: the solution for nursing and midwifery in Africa?

PMID- 10884171
TI  - The road we are travelling.

PMID- 10884172
TI  - Nurse practitioners: a safe and competent choice for primary care.

PMID- 10884173
TI  - California landmark law creates minimum nurse-to-patient ratios.

PMID- 10884174
TI  - A conversation with Dr Beverly Malone. A house big enough for all of us.
      Interview by Jan Harrington.

PMID- 10884175
TI  - Nursing: the number one health resource.

PMID- 10884176
TI  - Nursing and politics: a South African perspective.
AB  - The purpose of this paper is to provide a general introduction to politics, and
      to describe some political changes which have affected the rendering of
      multidisciplinary health care services in the Republic of South Africa since
      1994. Political issues which will be addressed include: changed provincial
      borders; opening up of the Republic of South Africa's international borders;
      increased emphasis on primary health care services; enhanced international
      involvement of the Republic of South Africa; changes in the statutory bodies
      governing the nursing profession; and changed legislation affecting health care
      workers. Political know-how is essential for professional survival. Unless nurses
      in the Republic of South Africa collaborate proactively as a united group
      representing the largest proportion of health care professionals in the country,
      the nursing profession and nursing education might become irrelevant to the
      political realities of the country and its people. Unless nurses can succeed in
      engaging in successful political debates and in negotiating their rights, they
      might become an increasingly voiceless, faceless and powerless female profession
      in the Republic of South Africa. However, politically knowledgeable nurses may
      help to ensure that the people will get the nurses and the nursing care they
      deserve, whilst the nurses will enjoy the benefits to which they are entitled,
      including market-related salaries.

PMID- 10884177
TI  - Shared Governance within the market-oriented health care system of New Zealand.
AB  - The New Zealand health reforms, announced in 1991 and implemented over the 3-year
      period 1992-1994, were market-oriented, following a competitive model that had
      been applied across New Zealand's public sector. Consideration is given to the
      effects of the health reforms on nursing and midwifery at Capital Coast Health
      Limited (CCHL), with the introduction of a market/economic model of health care
      and its accompanying managerialism. The market model, or the economic era of
      health care, as some describe it, created an environment where nurses felt
      powerless. All the directors of nursing and on-going hospital educational
      programs were disestablished in the public sector; nurses were disheartened,
      confused and lacked representation at senior management. Integral to, and
      accompanying, corporatization is managerialism. With corporatization, came
      managers from the non-health care sector who had no understanding of the
      complexities of health care. Accompanying managerialism is the notion that any
      able manager was capable of managing any agency, whether public or private.
      Naturally, there was an underlying conflict between the caring relationships and
      their related work in the clinical environment, and the desire for efficiency and
      economy. It seemed that we were dealing with contrasting themes of 'the market'
      and 'humanity' This led to further confusion and disempowerment, as the dollar
      gained prominence, for nursing has always been grounded in the 'humanities'. It
      was into this environment, after 5 years of the health reforms, that a Nurse
      Executive was appointed and the concept of Shared Governance was introduced. This
      article describes why Shared Governance was considered an appropriate model to
      introduce at CCHL, and identifies some of the tangible benefits being realized 18
      months post implementation. Discovering that membership in cross-organizational
      teams provides a mechanism for networking and creating a broader understanding of
      the organization has been but one of the major benefits.

PMID- 10884178
TI  - Congruence of terms between lists of problems and the ICNP--Alpha Version.
      International Classification for Nursing Practice.
AB  - The International Classification for Nursing Practice (ICNP)--Alpha Version, is
      the first rendition of the International Council of Nurses (ICN) efforts to
      develop a standardized international nursing language system. This system has
      three principal components: nursing phenomena; nursing actions; and nursing
      outcomes. This article describes a study of agreements between terms used by
      nurses of the intensive care unit at the Hospital of the University of Sao Paulo,
      to designate patients' nursing problems and the terms proposed by the ICNP--Alpha
      Version. The records of 59 interned patients, admitted to the intensive therapy
      unit, were analysed for nursing problems. Of 336 problem categories listed by the
      nurses, 153 (45.5%) corresponded to the ICNP terms. The 183 categories of
      problems that did not correspond to the ICNP terms were categorized by the
      authors as the following: medical diagnoses (37.2%); signs (28.4%); interventions
      (26.2%); and historical data (8.2%). These results show that there may be no
      agreement between the concept of nursing phenomena for the ICNP and of nursing
      problems for the nurses whose records were analysed. Considering that medical
      diagnoses, intervention and historical data could not be accepted as nursing
      phenomena for the ICNP, the agreement is potentially higher than 45.5%.

PMID- 10884179
TI  - Pay equity and nursing in Ontario: ten years later.
AB  - 'Nurses have never been compensated in accordance with their central role in
      health care' (Schreiber 1994), reflecting the generalized and well-documented
      under-valuing of the work of women (Schreiber 1993). Pay equity legislation,
      passed in Ontario, Canada in 1987, designed to correct gender wage
      discrimination, created great optimism that the under-valuing of nurses' work
      might be ending. Nonetheless, this has not been the case, as the social,
      political, and economic climate has not kept pace with the speed and enormity of
      social change necessary to enact the intent of the legislation. Indeed, gains in
      nurses' wages have been directly offset by significant lay-offs. In this paper,
      we examine the issues surrounding the implementation of pay equity legislation in
      Ontario, Canada, along with analysis and implications of these issues, drawn from
      10 years of experience. In addition, we highlight lessons that can be learned
      from the Ontario experience.

PMID- 10884180
TI  - Empowered nurses? Nurses in Norway and the USA compared.
AB  - This comparative study investigated to what degree nurses from two major
      university hospitals, one in the USA and one in Norway, experienced empowerment.
      Nurses' experiences of power were studied, as operationalized by Laschinger in
      her model and instruments. Laschinger's model is based on Kanter's theory of
      structural determinants of behaviour in organizations. The Norwegian sample
      consisted of 590 nurses with a response rate of 70.5%; the North American sample
      consisted of 135 nurses with a response rate of 55%. The results showed both
      similarities and differences. Formal power for both samples explained 51% of the
      variance of the overall empowerment, while informal and formal power explained
      62%. The Norwegian nurses experienced slightly more informal power while the USA
      nurses experienced more formal power. There were significant differences, in each
      hospital, in items within the theoretical constructs, when cross-tabulated by
      demographic variables. Leadership position was the demographic variable that most
      clearly differentiated in both hospital samples, with more power for the leaders.
      The small differences between nurses from two hospitals in two different
      countries in developed parts of the world raises some questions. The importance,
      or lack of importance, of cultural and organizational differences might be one
      area for further exploration. Overall, the methodology is valuable for further
      testing of nurse empowerment in different settings, as well as in change and
      implementation studies.

PMID- 10884181
TI  - A tale of teaching in two cities.
AB  - Internationally, nurses are health care educators, in institutions, clinics and
      field sites. This article describes a cross-cultural experience of sharing health
      care teaching methodologies, between a nurse from Israel and a small group of
      Ethiopian nurses in Addis Ababa. These nurses were working to prepare groups of
      Ethiopian Jews, through health education, for the transition to life in Israel.
      It is a prime example that nursing is without borders. This period of teaching
      produced a mutual learning experience of great value for the local nursing staff
      and visiting lecturer, which may provide useful insights for other nurses working
      in cross-cultural conditions.

PMID- 10884182
TI  - The sick euthyroid syndrome and the National Health Service: thyroxine alone is
      not the cure.

PMID- 10884183
TI  - Vitamin D receptor initiation codon polymorphism in Japanese patients with
      Graves' disease.
AB  - Recent studies have shown that related genetic influences on bone mineral density
      (BMD) and bone turnover are related to allelic variations in the vitamin D
      receptor (VDR) gene. Osteoporosis as a complication of hyperthyroidism is
      characterized by increased rates of both bone formation and bone resorption. In
      addition, VDR gene polymorphism influences susceptibility to some autoimmune
      diseases such as insulin-dependent diabetes mellitus (IDDM) and multiple
      sclerosis (MS). In the gene encoding the VDR, we investigated the distribution of
      a VDR-FokI polymorphism that changes the predicted protein sequence. The subjects
      were 131 female Japanese patients with Graves' disease and 150 female controls.
      The distribution of genotype frequencies differs between Graves' disease and
      controls (chi2 = 5.99, degrees of freedom = 2, p = 0.0386). We found
      overexpression of F allele (69% vs. 61%, p = 0.0472) and homozygote FF (48% vs.
      33%, p = 0.0118) in Graves' disease patients compared with controls. We also
      correlated a VDR-FokI polymorphism with BMD in the distal radius and biochemical
      markers of bone turnover in patients with Graves' disease in remission. Although
      generally no significant association was seen between age-adjusted BMD and
      genotype, patients in remission for >5 years showed significantly lower age
      adjusted BMD in Ff heterozygotes than in ff homozygotes (Z = 1.14 ff vs. Z = 
      0.43 Ff, p < 0.05). Moreover, serum concentrations of bone alkaline phosphatase
      were significantly greater in Ff homozygotes than in FF homozygotes (78 +/- 12
      vs. 59 +/- 10, p < 0.05). The genotypes did not differ in serum concentrations of
      osteocalcin, urinary hydroxyproline, or urinary deoxypyridinoline. Our results
      indicate, for the first time, an association between Graves' disease and a VDR
      polymorphism in the Japanese and suggest that a VDR-FokI polymorphism may affect
      bone mineral metabolism and can predict risk of osteoporosis as a complication of
      Graves' disease in patients in remission.

PMID- 10884184
TI  - Growth factor-expressing mast cells accumulate at the thyroid tissue-regenerative
      site of subacute thyroiditis.
AB  - The localization and biological roles of the multifunctional cell type mast cells
      remain unclear in subacute thyroiditis that is characterized by both epithelioid
      granuloma formation and thyroid tissue repair. We examined their
      immunolocalization with tryptase of a mast cell marker, using the biopsy
      specimens from 12 cases. In the epithelioid granuloma, no mast cells were
      detected in any of the cases, although a small number of them (4.6 +/- 2.4) were
      seen at the fibrous stroma around the granuloma in all cases. By contrast, in all
      cases, increased mast cells (28 +/- 7.2) localized at the thyroid tissue
      regenerative site where both thyroid folliculogenesis and angiogenesis take
      place. To elucidate possible roles of mast cells in the disease, we also examined
      their immunoexpressions of vascular endothelial cell growth factor (VEGF), basic
      fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF),
      transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF),
      which affect thyroid folliculogenesis and angiogenesis. In all 12 cases, mast
      cells displayed all of these growth factors in a manner not specific to the
      infiltrating site. The data suggest that growth factor-expressing mast cells may
      play crucial roles in the thyroid tissue repair of subacute thyroiditis,
      modulating thyroid folliculogenesis and angiogenesis; and that the
      multifunctionality of the cells may be partly dependent on their expressions of
      various growth factors.

PMID- 10884185
TI  - Congenital central isolated hypothyroidism caused by a homozygous mutation in the
      TSH-beta subunit gene.
AB  - We report a Belgian girl born in 1983 with isolated thyrotropin (TSH) deficiency.
      Hypothyroidism without goiter was diagnosed at the age of 2 months, with
      extremely low total thyroxine (T4) at 0.3 microg/dL (4 nmol/L; N[normal]: 5.6
      11.4 microg/dL). Basal TSH, only moderately elevated at 14.8 mU/L (N: 0-5.3;
      competitive radioimmunoassay, RIA), increased to 18.2 mU/L after thyrotropin
      releasing hormone (TRH) stimulation, whereas prolactin increased normally. At age
      15 years, after withdrawal of levothyroxine (LT4) therapy for 6 weeks, TRH
      stimulation slightly increased serum TSH using two immunometric assays, from less
      than 0.03 to 0.07 and from 0.2 to 0.3 (a monoclonal and polyclonal antibody), and
      from 1.9 to 4.1 mU/L using a polyclonal TSH antibody and iodinated recombinant
      TSH. Sequencing of the TSH-beta subunit gene revealed a homozygous single
      nucleotide deletion in codon 105 producing a frame shift that results in a
      truncated TSH-beta with nonhomologous 9 carboxyterminal amino acids and a loss of
      the 5 terminal residues. This mutation was previously reported in one Brazilian
      and two German families. The abnormal, and presumably biologically inactive, TSH
      can be detected in serum using appropriate antibodies. Its relatively small
      amount in serum is due to either reduced secretion or rapid degradation. The
      occurrence of the same mutation in three families of different ethnic origin
      suggests that this mutation may be prevalent in the population. Common ancestry
      or de novo mutations in a hot spot cannot be excluded. Finally, we must be aware
      that neonatal screening of congenital hypothyroidism based on blood spot TSH
      measurement will not detect this rare but severe genetic defect.

PMID- 10884186
TI  - Retinoic acid redifferentiation therapy for thyroid cancer.
AB  - For the treatment of differentiated thyroid cancer, surgery, radioiodide therapy,
      and thyrotropin-suppressive thyroxine application represent established
      therapeutic measures of proven efficiency, affording a good prognosis for this
      disease. However, in up to 30% of the cases, dedifferentiation is observed,
      giving rise to tumors that are refractory to conventional treatment. Eventually,
      this may lead to the most malignant human tumor, anaplastic thyroid carcinoma,
      with a life expectancy of only a few months after diagnosis. Among novel
      approaches for the treatment of dedifferentiated thyroid carcinomas, retinoic
      acid redifferentiation therapy was evaluated in several in vitro and in vivo
      studies. Cell culture experiments in thyroid carcinoma lines show that RA
      treatment affects thyroid specific functions (type I 5'-deiodinase, sodium/iodide
      symporter), cell-cell or cell-matrix interaction (intercellular adhesion molecule
      1, E-cadherin), differentiation markers (alkaline phosphatase, CD97), growth, and
      tumorigenicity. The observed changes, which involve multiple parameters that
      characterize a mature, functional thyrocyte, may be interpreted as partial
      redifferentiation. In clinical pilot studies, about 40% of the patients responded
      to RA application with an increased radioiodide uptake. In an evaluation of 20 RA
      treated patients with well-documented data sets, 8 exhibited a decrease (4) or
      stabilization (4) in tumor size and/or in serum thyroglobulin levels in addition
      to enhanced radioiodide transport. This indicates that these patients with a long
      history of unresponsiveness to other treatment may have experienced an actual
      therapeutic benefit. These data suggest that RA redifferentiation therapy,
      considering especially its comparatively mild side effects, may soon represent an
      alternative therapeutic approach to otherwise untreatable thyroid tumors.

PMID- 10884187
TI  - Fluorescent probes: looking backward and looking forward.
AB  - Probe technology has been advancing very rapidly but to study molecular events in
      real time, there has to be a discrete choice in the use of "probes" and the
      "labels" that they carry. In this minireview, we shed light on the use of
      fluorescent probes, especially the use of green fluorescent protein (GFP) and its
      variants as tools to cell biologists studying protein secretion and trafficking.
      The use of these GFP variants has further widened the application of Fluorescence
      Resonance Energy Transfer (FRET) in analyzing protein-protein interaction.

PMID- 10884188
TI  - Prevalence of C-cell hyperplasia in patients with normal basal and pentagastrin
      stimulated calcitonin.
AB  - The prevalence of thyroid C-cell hyperplasia (CCH) was investigated prospectively
      in 57 patients with normal preoperative pentagastrin-stimulated plasma
      concentrations of calcitonin (hCT, range, 1-60 pg/mL; normal, 100 pg/mL) who
      subsequently underwent total thyroidectomy due to thyrotoxicosis (n = 18) or to
      nodular thyroid disease in the presence (n = 9) or absence (n = 30) of
      cytological follicular neoplasia. CCH was seen in 28 of 57 (49%) of all patients.
      CCH was more common in hyperthyroid (12/18 [66%]) than in euthyroid (16/39 [41%]
      patients. No age- or gender-related differences in the occurrence of CCH was
      seen. There was no histological evidence of medullary thyroid carcinoma (MTC) in
      any patient. CCH classified histologically as neoplastic was encountered in two
      instances. It was concluded that CCH may be expected in almost 50% of
      normocalcitonemic patients with various thyroid disorders. Although the potential
      clinical importance of this histological finding and specifically its neoplastic
      variety remains unknown, these results are in keeping with the assumption that
      pentagastrin-stimulated plasma concentrations of hCT within the normal range do
      not exclude the presence of CCH.

PMID- 10884189
TI  - Serum insulin-like growth factor-I, insulin-like growth factor binding proteins,
      and bone mineral content in hyperthyroidism.
AB  - The mechanism by which thyroid hormones promote bone growth has not yet been
      elucidated. In vitro, thyroid hormones stimulate insulin-like growth factor-I
      (IGF-I) production by osteoblasts, which is important for the anabolic effects of
      the hormone on bone. To determine whether the IGF-I/IGF binding protein (IGFBP)
      profile is affected when thyroid hormone production is altered in vivo, we
      studied 36 women who had recently been diagnosed with hyperthyroidism (age: 29-67
      years; 19 with Graves' disease, 17 with toxic nodular goiter) and 36 age-matched
      healthy women as controls. Serum IGF-I, and its binding proteins (IGFBP-3, IGFBP
      4, and IGFBP-5), as well as bone mineral density (BMD) at the lumbar spine,
      femoral neck, and radius midshaft were measured before and 1 year after
      antithyroid (methimazole) treatment. Serum IGF-I levels were significantly
      increased in the hyperthyroid patients before treatment (214 +/- 18.2 ng/mL vs.
      145 +/- 21.3 ng/mL; p < 0.05). There was no difference in IGF-I levels of
      patients with Graves' disease and toxic nodular goiter. Serum IGF-I
      concentrations returned to normal after treatment with methimazole. Serum IGFBP-3
      and IGFBP-4 values were significantly elevated in the hyperthyroid group before
      treatment (3960 +/- 220 ng/mL and 749.7 +/- 53.1 ng/mL vs. 2701 +/- 180 ng/mL and
      489.9 +/- 32.4 ng/mL; p < 0.05 and p < 0.01, respectively) and were reduced to
      those of controls after treatment. Serum IGFBP-5 of hyperthyroid subjects was not
      different from that of controls either before or after therapy. Serum free
      thyroxine showed a positive correlation with serum levels of IGF-I (r = 0.73, p <
      0.05), IGFBP-3 (r = 0.59, p < 0.05), and IGFBP-4 (r = 0.67, p < 0.05) but not
      IGFBP-5. BMD at the radius midshaft was significantly lower in hyperthyroid
      patients at the start of the study and showed a positive correlation with serum
      IGF-I (r = 0.58; p < 0.001) and a negative correlation with IGFBP-4 (r = -0.61; p
      < 0.05). Radius BMD showed a 7.2% increase in the hyperthyroid group after 1 year
      of methimazole treatment, and the correlation between BMD and serum IGF-I
      disappeared. Our data indicate that thyroid hormones may influence the IGF
      I/IGFBP system in vivo in hyperthyroidism. The anabolic effects of increased
      levels of IGF-I may be limited in hyperthyroidism due to the increases of
      inhibitory IGFBPs that can counteract the anabolic effects and contribute to the
      observed net bone loss.

PMID- 10884190
TI  - Hypothyroidism after therapy for larynx and pharynx carcinoma.
AB  - Early detection of local and regional recurrence is the main goal during follow
      up of patients with larynx and pharynx cancer. Hypothyroidism occurring in those
      patients stays frequently undiagnosed as screening for hypothyroidism is not part
      of the routine follow-up. This study was performed to assess the prevalence of
      hypothyroidism in these patients. We included 120 patients (106 male, 14 female)
      with larynx or pharynx cancer treated more than 2 months earlier (mean = 41
      months) in the study. Cancer treatment consisted of either surgery (n = 44),
      radiotherapy (n = 15), or surgery combined with postoperative radiotherapy (n =
      61). In all patients, thyroid function studies (thyrotropin [TSH], free
      triiodothyronine [FT3], and free thyroxine [FT4]) were performed. Twenty-six of
      all patients (22%) were hypothyroid; in two patients hypothyroidism was diagnosed
      postoperatively and these two patients were on replacement therapy with thyroid
      hormones. The highest rate of hypothyroidism (34%) was present in patients
      treated with surgery combined with radiotherapy, whereas among patients treated
      with surgery only 7% were hypothyroid (p < 0.001). There was no difference in the
      duration of follow-up between therapy and inclusion in the study between those
      two groups. Two of 15 patients treated only with radiotherapy were diagnosed
      hypothyroid, but in this group the latency was shorter (p < 0.05). The results
      indicate that thyroid function studies should be routinely performed in the
      follow-up of head and neck cancer patients, especially if radiotherapy was part
      of the treatment.

PMID- 10884191
TI  - Appearance of antithyroglobulin antibodies as the sole sign of metastatic lymph
      nodes in a patient operated on for papillary thyroid cancer: a case report.
AB  - We report a case in which the appearance of a progressively rising titer of
      thyroglobulin (Tg) antibodies was the most sensitive marker of papillary thyroid
      cancer relapse at loco-regional lymph nodes. The patient, a 60-year-old man, had
      been treated with total thyroidectomy plus lymphadenectomy and radioiodine
      ablation for a 1-cm papillary thyroid cancer. Twelve years after surgery, while
      undergoing levothyroxine (LT4) therapy, Tg antibodies were first detected and
      progressively rose from 99 to 1,697 U/mL in 18 months, while serum Tg remained
      undetectable. Both neck ultrasonography and 131I whole-body scan (WBS) were
      unremarkable. Enlarged lymph nodes became palpable at the left laterocervical
      region only 2 years after the first appearance of Tg antibodies and were
      surgically removed after cancer relapse was confirmed by fine-needle aspiration
      cytology. This case emphasizes the possibility that in thyroid cancer patients
      who have undergone total thyroidectomy, the appearance of Tg antibodies may
      indicate metastatic lymph nodes even when serum Tg is undetectable and WBS
      negative.

PMID- 10884192
TI  - Advanced insular thyroid carcinoma in a fourteen-year-old girl: twenty-four years
      of follow-up.
AB  - Insular thyroid carcinoma has become a separate entity among thyroid
      malignancies. It is regarded as intermediate in aggressiveness between well
      differentiated and anaplastic thyroid carcinomas. Reports on the clinical course
      of children with insular thyroid carcinoma are rare. We report the case of a 14
      year-old girl who was admitted to our thyroid outpatient ward in 1975 with a
      scintigraphic cold thyroid nodule and multiple enlarged cervical lymph nodes.
      Chest radiography showed metastases in both lungs. After total thyroidectomy and,
      central and modified unilateral radical neck dissection, the girl was given a
      dose of 80 mCi 131I. Posttherapeutic scan demonstrated diffuse tracer uptake in
      both lungs. A second dose of 200 mCi 131I was administered 4 months later and
      another dose of 150 mCi 131I in July 1976. Subsequently, whole-body scans showed
      inconspicuous tracer distribution and chest x-rays were normal. The patient was
      treated with levothyroxine and followed until 1982, when she left Vienna. In
      1999, the patient was contacted for reexamination. She has been well and had had
      two healthy children. The patient was taking 150 microg levothyroxine daily; she
      had a normal TSH value and her thyroglubulin was 0.3 ng/mL. Chest radiography and
      sonography of the neck showed no pathological findings. The paraffin sections of
      the patient's tumor were reexamined in 1999 and demonstrated the histologic
      characteristics of a poorly differentiated insular thyroid carcinoma (pT4a, pN1a,
      M1). These findings demonstrate that even in advanced stages, insular thyroid
      carcinoma treatment can be successful.

PMID- 10884193
TI  - How should you choose a thyroid surgeon?

PMID- 10884194
TI  - Images in thyroidology. Hurthle cell carcinoma with cardiac metastasis.

PMID- 10884195
TI  - Serum interleukin-8 levels in thyroid diseases.

PMID- 10884196
TI  - Comparison of human and porcine TSH receptors.

PMID- 10884197
TI  - Hydroxyapatite and tricalcium phosphate-coated cups with and without screw
      fixation: a randomized study of 64 hips.
AB  - Sixty-two patients (64 hips) were provided with porous press-fit cups (Trilogy),
      plasma-sprayed with a coating consisting of 70% hydroxyapatite and 30% tricalcium
      phosphate. The patients were randomized to a cup with cluster holes for
      adjunctive screw fixation (n = 30) or to a cup without holes (n = 34).
      Radiostereometry was used to study migration and wear. Up to 2 years median
      translations and rotations <0.2 mm and <0.2 degrees were recorded in the 2
      groups, without any difference. The median annual proximal wear (0.11 and 0.12
      mm) was within the expected range despite the use of a ceramic coating, and it
      did not differ between the 2 designs. Radiolucent lines were frequently seen
      postoperatively but diminished during the follow-up without any sign of migration
      into the gaps. At 2 years, the median Harris scores were 99 points (range, 51-100
      points) in the group with and 98 points (range, 69-100 points) in the group
      without screws. The results indicate that early fixation can be achieved for
      ceramic-coated press-fit cups without using additional screw fixation.

PMID- 10884198
TI  - The results of retaining a well-fixed patellar component in revision total knee
      arthroplasty.
AB  - The results of revision total knee arthroplasty (TKA) in which a well-fixed
      patellar component was left in place (retained) were compared with those in which
      the patellar component was revised to a cemented all-polyethylene component. The
      patella was retained in 34 cases, 12 of which were metal-backed, and was revised
      in 39 cases. Data collected on all patients included a Knee Society clinical and
      radiographic score, SF36, a patellofemoral questionnaire, and a satisfaction
      survey. There were no differences in clinical score, responses to specific
      patellofemoral questions, or patient satisfaction between the 2 groups. Retaining
      a well-fixed patellar component at the time of revision TKA appears to be a
      viable option with equivalent short-term results to those obtained when the
      patellar component is revised.

PMID- 10884199
TI  - The AGC total knee prosthesis at average 11 years.
AB  - A retrospective study of a series of 126 consecutive primary cemented total knee
      replacements using the AGC prosthesis is reported. Sixty-two knees were available
      for long-term review with an average clinical follow-up of 11.4 years (range, 8.4
      13.6 years). The survivorship was 95%, defining the endpoint as revision of all
      components for any reason except sepsis. The average knee flexion was 110.9
      degrees. The average Knee Society score was 91, and the average Knee Society
      Functional score was 67. There was no finding of tibial polyethylene failure,
      wear debris-generated osteolysis, or tibial or femoral loosening. Seven metal
      backed patellae developed wear-through at an average of 80.4 months (7 of 126 for
      a 5.5% failure rate), with 3 (2.3%) resulting in complete revision. The authors
      continue to use the AGC prosthesis with an all-polyethylene patella. Compared
      with historical controls, the AGC has comparable survivorship.

PMID- 10884200
TI  - The patellofemoral joint in total knee arthroplasty: is the design of the
      trochlea the critical factor?
AB  - The outcome at 10 years is reported of a prospective study of 2 cohorts of total
      knee arthroplasties treated with (center A) or without (center B) patellar
      replacement. The same tibiofemoral components were used in all knees. The cohorts
      were demographically similar. A total of 124 patellae were treated by
      replacement, and 143 were treated without replacement. The clinical outcome and
      the patellofemoral revision rates were the same in the 2 cohorts: 1 patient
      required analgesia for anterior knee pain after replacement, and 1 without
      replacement required patellar replacement for pain. In the replaced group,
      patellofemoral survival on a best-case scenario was 100% at 10 years; on a worst
      case scenario, 96%. One of the unreplaced patellae had been resurfaced for pain
      by 10 years. In view of the satisfactory and similar outcomes with and without
      replacement, we suggest that an appropriate design for the prosthetic trochlea,
      rather than the replacement or otherwise of the patella, is the main determinant
      of patellofemoral outcome in total knee arthroplasty. Patella replacement may be
      optional. Desirable trochlea design features are described.

PMID- 10884201
TI  - Infected total knee arthroplasty treated by arthroscopic irrigation and
      debridement.
AB  - Sixteen patients with infected total knee arthroplasties (4 postoperative and 12
      late hematogenous) were treated by arthroscopic irrigation and debridement. All
      patients had < or = 7 days of knee symptoms, and there were no radiographic signs
      of osteitis or prosthetic loosening. Six of the 16 original total knee
      arthroplasties (38%) did not need prosthesis removal at a mean follow-up of 64
      months (range, 36-151 months). Ten other knees were treated with irrigation,
      debridement, and hardware removal within 7 weeks of the latest procedure used to
      try to retain components. Two (13%) of these cases ultimately required an
      arthrodesis for persistent infection. Although we still believe that this method
      is preferable to resorting immediately to implant removal for acute infections,
      arthroscopic debridement was less efficacious for most situations when compared
      with open treatment. We would use arthroscopic irrigation and debridement only
      under selected circumstances (medically unstable or anticoagulated patients).

PMID- 10884202
TI  - Fatal pulmonary embolism and mortality after revision of failed total hip
      arthroplasties.
AB  - To assess the effect of extensive surgery and delayed mobilization on
      postoperative incidence of fatal pulmonary embolism, we reviewed the mortality
      rate in 1,294 patients undergoing 1,483 revisions of failed total hip
      arthroplasties, in which mobilization of the patients was delayed for up to 3
      weeks. There were 6 deaths (mortality rate, 0.4%). All were submitted to autopsy;
      only 1 death was the result of pulmonary embolism. The results of our review do
      not support the view that more extensive surgery and delayed mobilization of the
      patient, as in revision of failed total hip arthroplasties, carries a high
      incidence of fatal pulmonary embolism.

PMID- 10884204
TI  - Are clinical and patient assessed outcomes affected by reducing length of
      hospital stay for total hip arthroplasty?
AB  - This prospective observational study investigated the relationship between the
      length of hospital stay (LOS) and outcomes at 3 months for primary total hip
      arthroplasty for osteoarthritis. Mean length of postoperative stay was 9.5 +/-
      2.8 days. Predictors of LOS were patient's age, sex, and number of comorbidities;
      preoperative Charnley scores and Nottingham Health Profile measures;
      complications; and hospital in which surgery took place. LOS was found to have a
      small negative correlation with outcome. The dominant association with improved
      outcome was the severity of the patients' impairment preoperatively. These data
      suggest that in situations in which adequate rehabilitation and support are
      available after discharge, a marginal reduction in postoperative LOS--from the
      average of 10.3 days observed at 1 hospital to the average of 8 days observed at
      another--would not adversely affect the short-term outcome.

PMID- 10884203
TI  - Results of an uncemented straight femoral shaft prosthesis after 9 years of
      follow-up.
AB  - The first consecutive 250 implantations of an uncemented, proximally anchored
      straight femoral shaft prosthesis (BiCONTACT) in 236 patients are included in
      this prospective follow-up study. Average time of follow-up evaluation was 8.9
      years (range, 7.4-10.7 years). At follow-up, 27 patients had died, and 2 could
      not be located. Seven patients underwent revision-2 for infection, 1 for
      recurrent dislocation, 2 for component undersizing with rapid subsidence, and 1
      for aseptic loosening of a varus-malaligned stem; 1 radiologically well-fixed
      stem had been revised during acetabular revision. Overall survival was 97.1%
      after 11 years (confidence limits, 98.7% [upper] and 93.6% [lower]). The average
      Harris Hip score at time of follow-up was 84.3 points. Radiologically, tiny
      reactive lines (<2 mm) were present in the distal zones of the femoral shaft, but
      no radiolucencies could be found in the proximal anchoring zone. The midterm to
      long-term follow-up results with the evaluated femoral component are encouraging
      and are comparable to those of modern techniques of cementing in primary total
      hip arthroplasty.

PMID- 10884205
TI  - Total knee arthroplasty after spontaneous osseous ankylosis and takedown of
      formal knee fusion.
AB  - This study compares the results of 16 total knee arthroplasties after a
      spontaneous osseous ankylosis and 14 total knee arthroplasties after a takedown
      of formal knee fusion. This series is a collection of patients who have either
      ankylosis or arthrodesis because of previous pyogenic or tuberculous infection.
      There were 18 women and 12 men. The age at operation ranged from 30 to 62 years
      (average, 42.9 years). The duration of ankylosis was longer in the patients in
      the spontaneous ankylosis group (19.7 years) than in the patients in the formally
      fused knee group (11.3 years). The duration from prior infection to arthroplasty
      was 12.4 years (range, 6-22 years) in the patients in the formally fused group
      and 20.4 years (range, 7-39 years) in the patients in the spontaneous ankylosis
      group. The original diagnosis was tuberculous arthritis in 14 knees and pyogenic
      arthritis in 16 knees. The average follow-up was 5.3 years (range, 5-6 years).
      Gender, age, diagnosis, and follow-up period were comparable in both groups. The
      preoperative Hospital for Special Surgery Knee Score was 60 in both groups, and
      the average knee score in both groups at the final follow-up was 73 (range, 67
      75). Comparison of the patient's preoperative and postoperative ambulatory status
      revealed functional improvement in both groups. The average range of active
      flexion in both groups was 75.8 degrees (range, 70 degrees-95 degrees). The
      extension lag in both groups averaged 9 degrees (range, 0 degrees-20 degrees).
      The range of motion was approximately the same in both groups. The angular
      deformity was corrected to 0 degrees to 10 degrees of valgus angulation in all
      knees. There was no revised prosthesis for loosening at the final follow-up.
      Complications included skin edge necrosis (53.3%), pyogenic infection in 2
      patients, and a quadriceps tendon rupture in 1 patient.

PMID- 10884206
TI  - Long-term survivorship of cemented all-polyethylene acetabular components in
      patients > 75 years of age.
AB  - Between 1974 and 1982, 132 consecutive hips in 112 patients >75 years of age were
      treated with primary total hip arthroplasty for osteoarthritis using a cemented
      all-polyethylene T28 socket and cemented T28 or TR28 stem with a 28-mm head size.
      At the time of review, 94 patients (110 hips [83%]) had died and 18 patients (22
      hips [17%]) were still living (mean age at follow-up, 93 years). Five hips (5
      patients) were lost to follow-up. Clinical follow-up averaged 8.9 years for the
      entire group and 14.6 years for patients still living. Only 2 acetabular
      components have been revised (1 for recurrent dislocation, 1 for infection). No
      acetabular component has required revision for aseptic loosening. Survivorship
      free of acetabular revision for aseptic loosening at 10 years was 100%; free of
      symptomatic acetabular loosening, 97.4% (95% confidence interval, 91.8-100%); and
      free of acetabular loosening, 95.9% (95% confidence interval, 89.7-100%). The
      commonest complication was postoperative hip dislocation, which occurred in 11
      hips (8.7%) and which required reoperation in 2 hips. Cemented acetabular
      components implanted in patients >75 years of age with a diagnosis of
      osteoarthritis showed a high rate of survivorship free of revision and free of
      symptomatic aseptic loosening.

PMID- 10884207
TI  - Irrigation and suction technique to ensure reliable cement penetration for total
      knee arthroplasty.
AB  - We describe a new technique to enhance the preparation of the cancellous bone
      surfaces in total knee arthroplasty using bone suction and pressure lavage
      irrigation. This technique provides dry bone surfaces on which to cement (which
      is particularly valuable if a tourniquet is not used) and improves significantly
      the penetration of cement into the tibial plateau as assessed on plain
      postoperative radiographs. We review the results of this new technique by
      analyzing depths of cement penetration on postoperative radiographs to assess
      whether this technique offers improvements in cement penetration and bone surface
      preparation. This technique offers a simple, quick, and reliable method of
      ensuring reliable cement penetration into the bony trabeculae during cemented
      total knee arthroplasty.

PMID- 10884208
TI  - Cost-effectiveness of immediate postoperative radiographs after uncomplicated
      total knee arthroplasty: a retrospective and prospective study of 750 patients.
AB  - We have questioned the value of postoperative radiographs after uncomplicated,
      primary total knee arthroplasty (TKA). A total of 750 patients were included in
      this 2-part study. In the first part, we retrospectively reviewed 200
      consecutive, primary TKAs to determine if the immediate postoperative radiographs
      offered any information that altered the clinical course or if these radiographs
      could serve as baselines for future images. In the second part, 550 patients who
      underwent an uncomplicated TKA had their first postoperative radiographs taken at
      the initial visit. These patients were followed prospectively until the 6-week
      follow-up appointment to determine if any events occurred in which predischarge
      radiographs would have been useful as a comparison study. Of the 200 patients who
      underwent a primary TKA, 192 had postoperative radiographs performed before
      discharge. Among the 192 patients, the radiographs did not alter the
      postoperative management. In examining overall quality of the radiographs, only
      36% were of sufficient quality to provide an accurate baseline for further
      studies. Total cost was approximately $36,000. In the 550 patients who had the
      first postoperative radiograph performed at 6 weeks, there were no instances in
      which radiographs taken before discharge were needed to aid in further management
      or legal defense. As with total hip arthroplasty, the past standard has been to
      obtain immediate postoperative radiographs after primary TKA. Although the
      information obtained in a total hip arthroplasty patient can be clinically
      important, the practice of obtaining routine, immediate postoperative knee
      radiographs in the absence of a specific clinical indication does not provide any
      additional clinical information and does not appear to benefit patient care.

PMID- 10884210
TI  - Does increased cement pressure produce superior femoral component fixation?
AB  - A new system of femoral cement pressurization is presented that attempts to
      produce sustained and elevated cement pressure. Five paired cadaver femora were
      pressurized with Simplex cement, and PFC femoral components were inserted. One of
      each pair was pressurized with the new system, and 1 was pressurized with an
      existing device. Pressure was recorded at the proximal and distal levels. After
      curing, all 10 specimens were sectioned at similar levels and subjected to push
      out testing to failure. Specimens that achieved higher pressures and longer
      duration of pressures tended to show higher levels of failure (not statistically
      proven on 10 specimens). Cementing techniques that use higher pressurization of
      cement are recommended. It is mandatory, however, that the femur be thoroughly
      cleaned of fat before the application of these techniques to avoid a fat embolism
      syndrome.

PMID- 10884209
TI  - A comparison of 2 modern femoral cementing techniques: analysis by cement-bone
      interface pressure measurements, computerized image analysis, and static
      mechanical testing.
AB  - Modern cementing techniques aim to improve microinterlock and to reduce aseptic
      loosening. The Norwegian and Swedish Arthroplasty Registers have shown an
      increased risk of revision using reduced-viscosity cement. We have compared 2
      modern cementing techniques using retrograde insertion of normal-viscosity and
      reduced-viscosity cements. Laboratory-simulated arthroplasty was performed in
      paired human femora. Performance was evaluated by measuring pressures generated
      during cementation, cement penetration, and shear strength of the prosthesis
      cement and bone-cement interfaces. Large differences exist between these 2 modern
      techniques. Despite no statistical differences between the pressure measurements
      with the 2 techniques, greater penetration of reduced-viscosity cement was found
      proximally, with a trend toward increased penetration of the more viscous cement
      distally. Areas of greater cement penetration with reduced-viscosity cement
      proximally produced higher values of ultimate shear strength. Both techniques
      showed a progressive increase in the shear strength as the level of the section
      progressed toward the tip of the prosthesis. There is a trend with both
      techniques for the distal fixation to be stronger.

PMID- 10884211
TI  - Cementless acetabular fixation in total hip arthroplasty using polyglycolide
      lactide screws: an in vivo canine study.
AB  - Bone ingrowth into cementless acetabular components was evaluated in a canine
      total hip arthroplasty model, comparing components initially stabilized with
      polyglycolide-lactide screws with those initially stabilized with titanium
      screws. The acetabular shell was anchored with 2 polyglycolide-lactide screws in
      16 dogs and with 2 titanium screws in 12 dogs. The dogs were followed and
      sacrificed at 7 weeks, 14 weeks, 10 months, or 15 months. Histomorphometric
      analysis of bone ingrowth into the weight-bearing dome of the acetabular shell
      was conducted. No difference was detected in mean bone ingrowth into the
      acetabular shell comparing the 2 screw groups. The results of this study do not
      support a significant advantage to the use of biodegradable screws for the
      initial stabilization of cementless acetabular components in canine total hip
      arthroplasty.

PMID- 10884212
TI  - Biomechanical study of the resurfacing hip arthroplasty: finite element analysis
      of the femoral component.
AB  - Finite element analysis was performed using 3-dimensional models to examine the
      biomechanical characteristics of the femoral component in resurfacing hip
      arthroplasty. Stress concentration was observed in the cortical bone adjacent to
      the rim of the prosthesis. Stress shielding was observed in the anterosuperior
      regions on the cancellous bone cross-sections near the cup rim. These
      biomechanical characteristics may lead to complications such as femoral neck
      fractures in patients with osteopenic bone and long-term loosening.

PMID- 10884213
TI  - The effect of joint loading on acetabular wear measurement in total hip
      arthroplasty.
AB  - All radiographic calculations of acetabular wear assume concentric reduction of
      the prosthetic articulation. To date, no studies have shown that the femoral head
      is fully reduced on standard radiographs, and we have seen cases on early
      postoperative radiographs in which this assumption is not met. Using our
      computerized radiographic technique, 78 paired anteroposterior pelvic radiographs
      in 46 patients at a mean of 14 months after surgery (range, 1-92 months) were
      evaluated with and without joint loading. Displacement with loading was analyzed
      against time since surgery, a surrogate for acetabular wear. Regression analysis
      found a statistically significant increase in femoral head displacement after
      loading with longer duration of follow-up, but the rate of this increase was
      small (0.027 mm/y). This difference affects calculated wear values by <15%. We
      conclude that in a low-wear cohort, joint loading does not affect radiographic
      calculations of acetabular polyethylene wear in a clinically important way.

PMID- 10884214
TI  - Changes in bone mineral density of the proximal femur after total knee
      arthroplasty.
AB  - This study investigates the relationship between total knee arthroplasty (TKA)
      and bone mineral density (BMD) in the same and opposite hips. The study
      prospectively evaluated 24 consecutive patients undergoing TKA (31 knees, 47
      hips). The mean follow-up was 48 months. The mean age at latest follow-up was 69
      years, and all patients had the preoperative diagnosis of osteoarthritis. BMD of
      the hip was measured by dual-energy x-ray absorptiometry. Despite a predicted age
      related loss of 4% during 2 years, 45% of the hips on the operative side and 59%
      of the hips on the nonoperative side had BMD higher than preoperative levels. Of
      hips, 81% on the operative side and 82% on the nonoperative side had BMD that was
      within the expected 4% age-related loss. Assuming that higher hip BMD may be
      protective against later hip fractures, the results infer that, by increasing hip
      BMD, TKA may be protective against later hip fractures. The increase with TKA in
      patient mobility and the increased hip loading may be a mechanism whereby the hip
      BMD increases.

PMID- 10884215
TI  - Fixation of periprosthetic femoral shaft fractures occurring at the tip of the
      stem: a biomechanical study of 5 techniques.
AB  - This study evaluated 5 currently used periprosthetic femoral shaft fracture
      fixation techniques to determine which technique provided the greatest fixation
      stability. Periprosthetic fractures in 30 synthetic femurs were fixed with a
      plate with cables, plate with proximal cables and distal bicortical screws (Ogden
      concept), plate with proximal unicortical screws and distal bicortical screws,
      plate with proximal unicortical screws and cables and distal bicortical screws,
      or 2 allograft cortical strut grafts with cables. These specimens were then
      tested in 3 physiologic loading modes. The plate constructs with proximal
      unicortical screws and distal bicortical screws or with proximal unicortical
      screws, proximal cables, and distal bicortical screws were significantly more
      stable in axial compression, lateral bending, and torsional loading than the
      other fixation constructs studied.

PMID- 10884216
TI  - Fracture of posterior-stablized tibial insert in a Genesis knee prosthesis.
AB  - We report a case of acute failure of a Genesis total knee arthroplasty (Smith and
      Nephew Orthopaedics, Memphis, TN) resulting from fracture of the eminence of the
      polyethylene posterior-stabilized tibial insert implanted in a revision
      procedure. A hyperflexion movement was responsible for shear stress on the insert
      with subsequent breakage. The correct diagnosis was obtained by arthroscopy, and
      the open substitution of the broken insert led to complete recovery of the
      prosthesis. This is the first report of mechanical breakage of a Genesis
      prosthesis.

PMID- 10884217
TI  - Pseudoaneurysm of femoral artery after revision total hip arthroplasty with a
      constrained cup.
AB  - Delayed vascular injury after revision total hip arthroplasty is a rare and
      unusual complication. We report a case of a mechanical complication in which
      migration of a constraining ring locking mechanism used during a revision total
      hip arthroplasty caused a pseudoaneurysm of the common femoral artery.

PMID- 10884218
TI  - False aneurysm 14 years after total hip arthroplasty.
AB  - Many reports of complications after total hip arthroplasty have been published
      concerning typical orthopaedic problems. Relatively little attention has been
      paid to serious vascular injuries, such as the development of a false aneurysm.
      To our knowledge, 10 cases have been described in the English literature. The
      mean time interval between surgery and initial manifestation of the aneurysm was
      9 months in these cases. Our patient developed first symptoms of a false aneurysm
      14 years after surgery. A minimally invasive technique was used to cut the
      aneurysm from perfusion. Removal of the total hip arthroplasty was performed
      through a retroperitoneal and lateral approach.

PMID- 10884219
TI  - Cementless total knee arthroplasty in ochronotic arthropathy: a case report with
      a 4-year follow-up.
AB  - Alkaptonuria is an inherited metabolic disorder characterized by the absence of
      the enzyme homogentisic acid oxidase, which leads to the accumulation of
      homogentisic acid, produced during normal metabolism of phenylalanine and
      tyrosine. Ochronosis, which is the dark pigmentation of connective tissues in
      patients with long-lasting alkaptonuria, can cause severe cartilage destruction
      in large joints and the vertebral column. Knee joint involvement, which occurs at
      relatively early ages, can be quite restrictive. Arthroplasty may be the
      treatment of choice in these patients because of limited mobility and diffuse
      involvement of the joint. We report a 48-year-old man who had been treated with
      cementless total knee arthroplasty. Theoretically, there are no bone ingrowth
      deficits that might be detrimental for the stabilization of cementless prostheses
      in ochronotic arthropathy because the bone tissue is not primarily affected by
      the disease. The 4-year follow-up of cementless total knee arthroplasty was
      satisfactory without any evidence of loosening.

PMID- 10884220
TI  - Taming superacids: stabilization of the fullerene cations HC60+ and C60.+.
AB  - A new superacid, H(CB11H6X6) (where X = chlorine or bromine), whose conjugate
      base is the exceptionally inert CB11H6X6- carborane anion, separates Bronsted
      acidity from oxidizing capacity and anion nucleophilicity in a manner not
      previously achieved. Reaction of this superacid with C60 gives HC60+ as a stable
      ion in solution and in the solid state. In a separate experiment, an oxidant was
      developed such that the long-sought C60.+ ion can be synthesized in solution. The
      preparation of these two fullerene carbocations is a notable departure from the
      prevalent chemistry of C60, which is dominated by the formation of anions or the
      addition of nucleophiles. The H(CB11H6X6) superacid overcomes the major
      limitations of presently known superacids and has potentially wide application.

PMID- 10884221
TI  - Subducted seamount imaged in the rupture zone of the 1946 nankaido earthquake
AB  - The Nankai Trough is a vigorous subduction zone where large earthquakes have been
      recorded since the seventh century, with a recurrence time of 100 to 200 years.
      The 1946 Nankaido earthquake was unusual, with a rupture zone estimated from long
      period geodetic data that was more than twice as large as that derived from
      shorter period seismic data. In the center of this earthquake rupture zone, we
      used densely deployed ocean bottom seismographs to detect a subducted seamount 13
      kilometers thick by 50 kilometers wide at a depth of 10 kilometers. We propose
      that this seamount might work as a barrier inhibiting brittle seismogenic
      rupture.

PMID- 10884222
TI  - Interconnected feedback loops in the Neurospora circadian system.
AB  - In Neurospora crassa, white collar 1 (WC-1), a transcriptional activator and
      positive clock element, is rhythmically expressed from a nonrhythmic steady-state
      pool of wc-1 transcript, consistent with posttranscriptional regulation of
      rhythmicity. Mutations in frq influence both the level and periodicity of WC-1
      expression, and driven FRQ expression not only depresses its own endogenous
      levels, but positively regulates WC-1 synthesis with a lag of about 8 hours, a
      delay similar to that seen in the wild-type clock. FRQ thus plays dual roles in
      the Neurospora clock and thereby, with WC-1, forms a second feedback loop that
      would promote robustness and stability in this circadian system. The existence
      also of interlocked loops in Drosophila melanogaster and mouse clocks suggests
      that such interlocked loops may be a conserved aspect of circadian timing
      systems.

PMID- 10884223
TI  - An empirical assessment of taxic paleobiology.
AB  - The analysis of major changes in faunal diversity through time is a central theme
      of analytical paleobiology. The most important sources of data are literature
      based compilations of stratigraphic ranges of fossil taxa. The levels of error in
      these compilations and the possible effects of such error have often been
      discussed but never directly assessed. We compared our comprehensive database of
      trilobites to the equivalent portion of J. J. Sepkoski Jr.'s widely used global
      genus database. More than 70% of entries in the global database are inaccurate;
      however, as predicted, the error is randomly distributed and does not introduce
      bias.

PMID- 10884224
TI  - Cooperative regulation of cell polarity and growth by Drosophila tumor
      suppressors.
AB  - Loss of cell polarity and tissue architecture are characteristics of malignant
      cancers derived from epithelial tissues. We provide evidence from Drosophila that
      a group of membrane-associated proteins act in concert to regulate both
      epithelial structure and cell proliferation. Scribble (Scrib) is a cell junction
      localized protein required for polarization of embryonic and, as demonstrated
      here, imaginal disc and follicular epithelia. We show that the tumor suppressors
      lethal giant larvae (lgl) and discs-large (dlg) have identical effects on all
      three epithelia, and that scrib also acts as a tumor suppressor. Scrib and Dlg
      colocalize and overlap with Lgl in epithelia; activity of all three genes is
      required for cortical localization of Lgl and junctional localization of Scrib
      and Dlg. scrib, dlg, and lgl show strong genetic interactions. Our data indicate
      that the three tumor suppressors act together in a common pathway to regulate
      cell polarity and growth control.

PMID- 10884225
TI  - Molecular identification of a taste receptor gene for trehalose in Drosophila.
AB  - The molecular nature of sweet taste receptors has not been fully explored.
      Employing a differential screening strategy, we identified a taste receptor gene,
      Tre1, that controls the taste sensitivity to trehalose in Drosophila
      melanogaster. The Tre1 gene encodes a novel protein with similarity to G protein
      coupled seven-transmembrane receptors. Disruption of the Tre1 gene lowered the
      taste sensitivity to trehalose, whereas sensitivities to other sugars were
      unaltered. Overexpression of the Tre1 gene restored the taste sensitivity to
      trehalose in the Tre1 deletion mutant. The Tre1 gene is expressed in taste
      sensory cells. These results provide direct evidence that Tre1 encodes a putative
      taste receptor for trehalose in Drosophila.

PMID- 10884226
TI  - Activating mineralocorticoid receptor mutation in hypertension exacerbated by
      pregnancy.
AB  - Hypertension and pregnancy-related hypertension are major public health problems
      of largely unknown causes. We describe a mutation in the mineralocorticoid
      receptor (MR), S810L, that causes early-onset hypertension that is markedly
      exacerbated in pregnancy. This mutation results in constitutive MR activity and
      alters receptor specificity, with progesterone and other steroids lacking 21
      hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural
      and biochemical studies indicate that the mutation results in the gain of a van
      der Waals interaction between helix 5 and helix 3 that substitutes for
      interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type
      receptor. This helix 5-helix 3 interaction is highly conserved among diverse
      nuclear hormone receptors, suggesting its general role in receptor activation.

PMID- 10884227
TI  - Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+
      channels.
AB  - The structure of the cytoplasmic assembly of voltage-dependent K+ channels was
      solved by x-ray crystallography at 2.1 angstrom resolution. The assembly includes
      the cytoplasmic (T1) domain of the integral membrane alpha subunit together with
      the oxidoreductase beta subunit in a fourfold symmetric T1(4)beta4 complex. An
      electrophysiological assay showed that this complex is oriented with four T1
      domains facing the transmembrane pore and four beta subunits facing the
      cytoplasm. The transmembrane pore communicates with the cytoplasm through
      lateral, negatively charged openings above the T1(4)beta4 complex. The
      inactivation peptides of voltage-dependent K(+) channels reach their site of
      action by entering these openings.

PMID- 10884228
TI  - Three-dimensional structure of the Tn5 synaptic complex transposition
      intermediate.
AB  - Genomic evolution has been profoundly influenced by DNA transposition, a process
      whereby defined DNA segments move freely about the genome. Transposition is
      mediated by transposases, and similar events are catalyzed by retroviral
      integrases such as human immunodeficiency virus-1 (HIV-1) integrase.
      Understanding how these proteins interact with DNA is central to understanding
      the molecular basis of transposition. We report the three-dimensional structure
      of prokaryotic Tn5 transposase complexed with Tn5 transposon end DNA determined
      to 2.3 angstrom resolution. The molecular assembly is dimeric, where each double
      stranded DNA molecule is bound by both protein subunits, orienting the transposon
      ends into the active sites. This structure provides a molecular framework for
      understanding many aspects of transposition, including the binding of transposon
      end DNA by one subunit and cleavage by a second, cleavage of two strands of DNA
      by a single active site via a hairpin intermediate, and strand transfer into
      target DNA.

PMID- 10884229
TI  - fw2.2: a quantitative trait locus key to the evolution of tomato fruit size.
AB  - Domestication of many plants has correlated with dramatic increases in fruit
      size. In tomato, one quantitative trait locus (QTL), fw2.2, was responsible for a
      large step in this process. When transformed into large-fruited cultivars, a
      cosmid derived from the fw2.2 region of a small-fruited wild species reduced
      fruit size by the predicted amount and had the gene action expected for fw2.2.
      The cause of the QTL effect is a single gene, ORFX, that is expressed early in
      floral development, controls carpel cell number, and has a sequence suggesting
      structural similarity to the human oncogene c-H-ras p21. Alterations in fruit
      size, imparted by fw2.2 alleles, are most likely due to changes in regulation
      rather than in the sequence and structure of the encoded protein.

PMID- 10884230
TI  - Stellar production rates of carbon and its abundance in the universe.
AB  - The bulk of the carbon in our universe is produced in the triple-alpha process in
      helium-burning red giant stars. We calculated the change of the triple-alpha
      reaction rate in a microscopic 12-nucleon model of the (12)C nucleus and looked
      for the effects of minimal variations of the strengths of the underlying
      interactions. Stellar model calculations were performed with the alternative
      reaction rates. Here, we show that outside a narrow window of 0.5 and 4% of the
      values of the strong and Coulomb forces, respectively, the stellar production of
      carbon or oxygen is reduced by factors of 30 to 1000.

PMID- 10884231
TI  - Topographic mapping of the quantum hall liquid using a few-electron bubble
AB  - A scanning probe technique was used to obtain a high-resolution map of the random
      electrostatic potential inside the quantum Hall liquid. A sharp metal tip,
      scanned above a semiconductor surface, sensed charges in an embedded two
      dimensional (2D) electron gas. Under quantum Hall effect conditions, applying a
      positive voltage to the tip locally enhanced the 2D electron density and created
      a "bubble" of electrons in an otherwise unoccupied Landau level. As the tip
      scanned along the sample surface, the bubble followed underneath. The tip sensed
      the motions of single electrons entering or leaving the bubble in response to
      changes in the local 2D electrostatic potential.

PMID- 10884232
TI  - Carbon nanotube-based nonvolatile random access memory for molecular computing
AB  - A concept for molecular electronics exploiting carbon nanotubes as both molecular
      device elements and molecular wires for reading and writing information was
      developed. Each device element is based on a suspended, crossed nanotube geometry
      that leads to bistable, electrostatically switchable ON/OFF states. The device
      elements are naturally addressable in large arrays by the carbon nanotube
      molecular wires making up the devices. These reversible, bistable device elements
      could be used to construct nonvolatile random access memory and logic function
      tables at an integration level approaching 10(12) elements per square centimeter
      and an element operation frequency in excess of 100 gigahertz. The viability of
      this concept is demonstrated by detailed calculations and by the experimental
      realization of a reversible, bistable nanotube-based bit.

PMID- 10884233
TI  - Electrochemical micromachining
AB  - The application of ultrashort voltage pulses between a tool electrode and a
      workpiece in an electrochemical environment allows the three-dimensional
      machining of conducting materials with submicrometer precision. The principle is
      based on the finite time constant for double-layer charging, which varies
      linearly with the local separation between the electrodes. During nanosecond
      pulses, the electrochemical reactions are confined to electrode regions in close
      proximity. This technique was used for local etching of copper and silicon as
      well as for local copper deposition.

PMID- 10884234
TI  - Should GMC leaders be put to the sword? No, doctors must work together.

PMID- 10884235
TI  - Treatment of stable angina. Use drugs before percutaneous transluminal coronary
      angioplasty.

PMID- 10884236
TI  - A "common sense revolution" for UK health care? The conservatives unveil their
      latest plans.

PMID- 10884237
TI  - Intranasal midazolam for febrile seizures. A step forward in treating a common
      and distressing condition.

PMID- 10884238
TI  - Bupropion: a new treatment for smokers. Nicotine replacement treatment should
      also be available on the NHS.

PMID- 10884239
TI  - UN says up to half the teenagers in Africa will die of AIDS.

PMID- 10884240
TI  - Mbeki dismisses "Durban declaration".

PMID- 10884241
TI  - Whistleblower inquiry clears british hospital

PMID- 10884242
TI  - Surgeon vows to fight injunction

PMID- 10884243
TI  - In brief

PMID- 10884244
TI  - BMA's annual meeting expresses "no confidence" in GMC

PMID- 10884245
TI  - Japan plans to monitor medical mishaps

PMID- 10884247
TI  - Minocycline slows progress of Huntington's disease in mice

PMID- 10884246
TI  - New york votes to post doctors' details on net

PMID- 10884248
TI  - US court refutes Nebraska's antiabortion law

PMID- 10884249
TI  - France bans morning after pill from schools

PMID- 10884250
TI  - US doctors win round in battle for right to negotiate with HMOs

PMID- 10884251
TI  - Fraud study concludes that self regulation has failed

PMID- 10884252
TI  - Slovak president's fight for life raises health care fears

PMID- 10884253
TI  - Hospital doctors face rising threat of suspension.

PMID- 10884255
TI  - Tolerating tolerability

PMID- 10884254
TI  - Percutaneous transluminal coronary angioplasty versus medical treatment for non
      acute coronary heart disease: meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: To determine whether percutaneous transluminal coronary angioplasty
      (angioplasty) is superior to medical treatment in non-acute coronary artery
      disease. DESIGN: Meta-analysis of randomised controlled trials. SETTING:
      Randomised controlled trials conducted worldwide and published between 1979 and
      1998. PARTICIPANTS: 953 patients treated with angioplasty and 951 with medical
      treatment from six randomised controlled trials, three of which included patients
      with multivessel disease and pre-existing myocardial infarction. MAIN OUTCOME
      MEASURES: Angina, fatal and non-fatal myocardial infarction, death, repeated
      angioplasty, and coronary artery bypass grafting. RESULTS: In patients treated
      with angioplasty compared with medical treatment the risk ratios were 0. 70 (95%
      confidence interval 0.50 to 0.98; heterogeneity P<0.001) for angina; 1.42 (0.90
      to 2.25) for fatal and non-fatal myocardial infarction, 1.32 (0.65 to 2.70) for
      death, 1.59 (1.09 to 2.32) for coronary artery bypass graft, and 1.29 (0.71 to
      3.36; heterogeneity P<0.001) for repeated angioplasty. Differences in the
      methodological quality of the trials, in follow up, or in single versus
      multivessel disease did not explain the variability in study results in any
      analysis. CONCLUSIONS: Percutaneous transluminal coronary angioplasty may lead to
      a greater reduction in angina in patients with coronary heart disease than
      medical treatment but at the cost of more coronary artery bypass grafting. Trials
      have not included enough patients for informative estimates of the effect of
      angioplasty on myocardial infarction, death, or subsequent revascularisation,
      though trends so far do not favour angioplasty.

PMID- 10884256
TI  - Prevalence of antibodies to hepatitis B, hepatitis C, and HIV and risk factors in
      Irish prisoners: results of a national cross sectional survey.
AB  - OBJECTIVES: To determine the prevalence of antibodies to hepatitis B core
      antigen, hepatitis C virus, and HIV in the prison population of the Republic of
      Ireland and to examine risk factors for infection. DESIGN: Cross sectional,
      anonymous, unlinked survey, with self completed risk factor questionnaire and
      provision of oral fluid specimen for antibody testing. SETTING: Nine of the 15
      prisons in the Republic of Ireland. PARTICIPANTS: 1366 prisoners, of whom 1205
      (57 women) participated. In the smaller prisons all prisoners were surveyed,
      while in the three largest prisons one half of the population was randomly
      sampled. Three small prisons believed not to have a problem with injecting drug
      use were excluded. MAIN OUTCOME MEASURES: Prevalence of antibodies to hepatitis B
      core antigen, antibodies to hepatitis C virus, and antibodies to HIV. Self
      reported risk factor status. RESULTS: Prevalence of antibodies to hepatitis B
      core antigen was 104/1193 (8.7%; 95% confidence interval 7.2% to 10.5%), to
      hepatitis C virus, 442/1193 (37%; 34.3% to 39.9%), and to HIV, 24/1193 (2%; 1.3%
      to 3%). The most important predictor of being positive for hepatitis B and
      hepatitis C was a history of injecting drug use. Thirty four women (60%) and 474
      men (42%) reported ever injecting drugs. A fifth (104) of 501 injecting drug
      users reported first injecting in prison, and 347 (71%) users reported sharing
      needles in prison. CONCLUSIONS: Infection with hepatitis C secondary to use of
      injected drugs is endemic in Irish prisons. Better access to harm reduction
      strategies is needed in this environment.

PMID- 10884257
TI  - Comparison of intranasal midazolam with intravenous diazepam for treating febrile
      seizures in children: prospective randomised study.
AB  - OBJECTIVE: To compare the safety and efficacy of midazolam given intranasally
      with diazepam given intravenously in the treatment of children with prolonged
      febrile seizures. DESIGN: Prospective randomised study. SETTING: Paediatric
      emergency department in a general hospital. SUBJECTS: 47 children aged six months
      to five years with prolonged febrile seizure (at least 10 minutes) during a 12
      month period. INTERVENTIONS: Intranasal midazolam (0.2 mg/kg) and intravenous
      diazepam (0.3 mg/kg). MAIN OUTCOME MEASURES: Time from arrival at hospital to
      starting treatment and cessation of seizures. RESULTS: Intranasal midazolam and
      intravenous diazepam were equally effective. Overall, 23 of 26 seizures were
      controlled with midazolam and 24 out of 26 with diazepam. The mean time from
      arrival at hospital to starting treatment was significantly shorter in the
      midazolam group (3.5 (SD 1.8) minutes, 95% confidence interval 3.3 to 3.7) than
      the diazepam group (5.5 (2.0), 5.3 to 5.7). The mean time to control of seizures
      was significantly sooner (6.1 (3.6), 6.3 to 6.7) in the midazolam group than the
      diazepam group (8.0 (0.5), 7. 9 to 8.3). No significant side effects were
      observed in either group. CONCLUSION: Seizures were controlled more quickly with
      intravenous diazepam than with intranasal midazolam, although midazolam was as
      safe and effective as diazepam. The overall time to cessation of seizures after
      arrival at hospital was faster with intranasal midazolam than with intravenous
      diazepam. The intranasal route can possibly be used not only in medical centres
      but in general practice and, with appropriate instructions, by families of
      children with recurrent febrile seizures at home.

PMID- 10884258
TI  - Orlistat associated with hypertension.

PMID- 10884259
TI  - Word association: hepatitis, eh?

PMID- 10884261
TI  - Up close and personal

PMID- 10884260
TI  - Intergenerational 20 year trends in the prevalence of asthma and hay fever in
      adults: the Midspan family study surveys of parents and offspring.
AB  - OBJECTIVE: To estimate trends between 1972-6 and 1996 in the prevalences of
      asthma and hay fever in adults. DESIGN: Two epidemiological surveys 20 years
      apart. Identical questions were asked about asthma, hay fever, and respiratory
      symptoms at each survey. SETTING: Renfrew and Paisley, two towns in the west of
      Scotland. SUBJECTS: 1,477 married couples aged 45-64 participated in a general
      population survey in 1972-6; and 2,338 offspring aged 30-59 participated in a
      1996 survey. Prevalences were compared in 1,708 parents and 1,124 offspring aged
      45-54. MAIN OUTCOME MEASURES: Prevalences of asthma, hay fever, and respiratory
      symptoms. RESULTS: In never smokers, age and sex standardised prevalences of
      asthma and hay fever were 3.0% and 5.8% respectively in 1972-6, and 8.2% and 19.
      9% in 1996. In ever smokers, the corresponding values were 1.6% and 5.4% in 1972
      6 and 5.3% and 15.5% in 1996. In both generations, the prevalence of asthma was
      higher in those who reported hay fever (atopic asthma). In never smokers, reports
      of wheeze not labelled as asthma were about 10 times more common in 1972-6 than
      in 1996. With a broader definition of asthma (asthma and/or wheeze), to minimise
      diagnostic bias, the overall prevalence of asthma changed little. However,
      diagnostic bias mainly affected non-atopic asthma. Atopic asthma increased more
      than twofold (prevalence ratio 2.52 (95% confidence interval 1.01 to 6.28))
      whereas the prevalence of non-atopic asthma did not change (1.00 (0.53 to 1.90)).
      CONCLUSION: The prevalence of asthma in adults has increased more than twofold in
      20 years, largely in association with trends in atopy, as measured indirectly by
      the prevalence of hay fever. No evidence was found for an increase in diagnostic
      awareness being responsible for the trend in atopic asthma, but increased
      awareness may account for trends in non-atopic asthma.

PMID- 10884262
TI  - Science, medicine, and the future: Tolerance and autoimmunity.

PMID- 10884264
TI  - Death of professor thomas jones

PMID- 10884263
TI  - ABC of oral health. Oral cancer.

PMID- 10884265
TI  - Conflict and health. Public health and humanitarian interventions: developing the
      evidence base.

PMID- 10884266
TI  - Tragic choices and the role of administrative law.

PMID- 10884267
TI  - Obituaries

PMID- 10884268
TI  - The BMA's annual representative meeting

PMID- 10884269
TI  - Doctors afield

PMID- 10884270
TI  - The sweetness of life

PMID- 10884271
TI  - All gloss and noise

PMID- 10884273
TI  - Helping the general medical council

PMID- 10884272
TI  - Angioplasty

PMID- 10884275
TI  - A good week for drugs

PMID- 10884274
TI  - Beware cloth devils

PMID- 10884276
TI  - Angioplasty may be no better than medical treatment for non-acute heart disease

PMID- 10884277
TI  - Drug use and hepatitis are endemic in irish prisons

PMID- 10884279
TI  - Prevalence of atopic asthma in adults has increased

PMID- 10884278
TI  - Intranasal midazolam effectively treats febrile seizures in children

PMID- 10884280
TI  - Humanitarian aid needs a better evidence base

PMID- 10884281
TI  - The courts will challenge medical decisions that are not made fairly

PMID- 10884282
TI  - Working on morale

PMID- 10884283
TI  - Comparative analysis of lipid composition of normal and acute-phase high density
      lipoproteins.
AB  - In the acute-phase response and in diseases with prolonged acute phases, normal
      HDL (NHDL) is converted into acute-phase HDL (APHDL) and becomes proinflammatory
      and unable to protect LDL against oxidative modification. Earlier work had
      demonstrated that these changes are associated with alterations in apolipoprotein
      composition and enzymatic activity of APHDL, but the effect of the acute-phase
      condition on the lipid composition of APHDL had remained obscure. The present
      study shows marked quantitative differences in lipid composition between NHDL and
      APHDL. Specifically, APHDL contained 25% less total lipid per milligram of
      protein. Up to 50% of cholesteryl ester in the lipid core of APHDL was replaced
      by triacylglycerol; however, the total phospholipid/total neutral lipid ratios
      were the same as in NHDL, both lipoproteins giving similar calculated lipid core
      radii. Furthermore, the phosphatidylcholine/sphingomyelin ratio in APHDL was
      nearly double that in NHDL, indicating a relative loss of sphingomyelin. A
      decrease was also seen in diacyl and alkenylacyl glycerophosphatidylethanolamine
      as well as in phosphatidylinositol of APHDL when compared with NHDL. APHDL
      contained proportionally more saturated and less polyunsaturated and isoprostane
      containing species of phosphatidylcholine, as well as more saturated than
      unsaturated cholesteryl esters. APHDL also contained significantly more free
      fatty acids, lysophosphatidylcholine, and free cholesterol. These changes in the
      lipid composition of HDL are consistent with the alterations in the apoprotein
      composition and enzymatic activity of APHDL and indicate proinflammatory and
      proatherogenic roles for APHDL.

PMID- 10884284
TI  - Diurnal and dietary-induced changes in cholesterol synthesis correlate with
      levels of mRNA for HMG-CoA reductase.
AB  - We determined the extent to which diurnal variation in cholesterol synthesis in
      liver is controlled by steady-state mRNA levels for the rate-limiting enzyme in
      the pathway, hydroxymethylglutaryl (HMG)-CoA reductase. Rats 30 days of age and
      maintained on a low-cholesterol diet since weaning were injected
      intraperitoneally with (3)H(2)O. The specific radioactivity of the whole-body
      water pool soon became constant, allowing for expression of values for
      incorporation of label into cholesterol as absolute rates of cholesterol
      synthesis. In liver, there was a peak of cholesterol synthesis from 8 pm to
      midnight, a 4-fold increase over synthesis rates from 8 am to noon. Increases in
      synthesis were quantitatively in lock step with increases in mRNA levels for HMG
      CoA reductase occurring 4 h earlier. In a parallel experiment, rats received 1%
      cholesterol in the diet from weaning to 30 days of age. Basal levels of hepatic
      cholesterol synthesis were greatly diminished and there was little diurnal
      variation of cholesterol synthesis or of levels of mRNA for HMG-CoA reductase.
      Levels of mRNA for the low density lipoprotein receptor and scavenger receptor-B1
      (putative high density lipoprotein receptor) showed little diurnal variation,
      regardless of diet. This suggests that diurnal variation of hepatic cholesterol
      synthesis is driven primarily by varying the steady-state mRNA levels for HMG-CoA
      reductase. Other tissues were also examined. Adrenal gland also showed a 4-fold
      diurnal increase in accumulation of recently synthesized cholesterol. In contrast
      to liver, however, there was little corresponding change in mRNA expression for
      HMG-CoA reductase. Much of this newly synthesized cholesterol may be of hepatic
      origin, imported into adrenal by SR-B1, whose mRNA was up-regulated 2-fold. In
      brain, there was no diurnal variation in either cholesterol synthesis or mRNA
      expression, and no influence of high- or low-cholesterol diets on synthesis rates
      or HMG-CoA reductase mRNA levels.

PMID- 10884285
TI  - Increased uptake of alpha-hydroxy aldehyde-modified low density lipoprotein by
      macrophage scavenger receptors.
AB  - Reactive aldehydes can be formed during the oxidation of lipids, glucose, and
      amino acids and during the nonenzymatic glycation of proteins. Low density
      lipoprotein (LDL) modified with malondialdehyde are taken up by scavenger
      receptors on macrophages. In the current studies we determined whether alpha
      hydroxy aldehydes also modify LDL to a form recognized by macrophage scavenger
      receptors. LDL modified by incubation with glycolaldehyde, glyceraldehyde,
      erythrose, arabinose, or glucose (alpha-hydroxy aldehydes that possess two,
      three, four, five, and six carbon atoms, respectively) exhibited decreased free
      amino groups and increased mobility on agarose gel electrophoresis. The lower the
      molecular weight of the aldehyde used for LDL modification, the more rapid and
      extensive was the derivatization of free amino groups. Approximately 50-75% of
      free lysine groups in LDL were modified after incubation with glyceraldehyde,
      glycolaldehyde, or erythrose for 24-48 h. Less extensive reductions in free amino
      groups were observed when LDL was incubated with arabinose or glucose, even at
      high concentration for up to 5 days. LDL modified with glycolaldehyde and
      glyceraldehyde labeled with (125)I was degraded more extensively by human
      monocyte-derived macrophages than was (125)I-labeled native LDL. Conversely, LDL
      modified with (125)I-labeled erythrose, arabinose, or glucose was degraded less
      rapidly than (125)I-labeled native LDL. Competition for the degradation of LDL
      modified with (125)I-labeled glyceraldehyde was nearly complete with acetyl-,
      glycolaldehyde-, and glyceraldehyde-modified LDL, fucoidin, and advanced
      glycation end product-modified bovine serum albumin, and absent with unlabeled
      native LDL. These results suggest that short-chain alpha-hydroxy aldehydes react
      with amino groups on LDL to yield moieties that are important determinants of
      recognition by macrophage scavenger receptors.

PMID- 10884286
TI  - Leukocyte CD11b expression is not essential for the development of
      atherosclerosis in mice.
AB  - CD11b is an alpha chain of the leukocyte beta(2)-integrin, Mac-1, which mediates
      binding and extravasation of leukocytes. Because this event is critical in
      atherosclerosis, we examined the role of CD11b in lesion formation.
      Atherosclerosis-susceptible, low density lipoprotein receptor-deficient (LDL-R(
      /)-) mice were irradiated and repopulated with bone marrow cells from CD11b
      deficient (CD11b(-/)-) mice. After 4 weeks, <2% of the peripheral blood
      leukocytes of the CD11b(-/)- bone marrow-transplanted LDL-R(-/)- mice expressed
      CD11b, whereas approximately 25% of the CD11b(+/)+ bone marrow-transplanted LDL
      R(-/)- mice expressed CD11b. After consuming a high-fat diet for 16 weeks the
      mean lesion aortic valve area, cholesterol accumulation in the aorta, and the
      degree of intimal macrophage infiltration were similar in mice reconstituted with
      either CD11b(+)(/+) or CD11b(-/)- bone marrow cells. The studies confirm that
      CD11b expression of bone marrow-derived cells does not influence the development
      of atherosclerosis in hypercholesterolemic LDL-R(-/)- mice.

PMID- 10884287
TI  - Adipose tissue deficiency, glucose intolerance, and increased atherosclerosis
      result from mutation in the mouse fatty liver dystrophy (fld) gene.
AB  - The fatty liver dystrophy (fld) mutant mouse is characterized by neonatal fatty
      liver and hypertriglyceridemia that resolve at weaning, and neuropathy affecting
      peripheral nerve in adulthood. We now report additional significant
      manifestations of this single gene mutation, which include adipose tissue
      deficiency, glucose intolerance, and increased susceptibility to atherosclerosis.
      In adult fld/fld mice, both white and brown fat pads exhibit an 80% reduction in
      mass compared with wild-type controls, and consist of immature adipocytes as
      assessed by morphological and molecular criteria. The lack of lipid accumulation
      in fld/fld adipose tissue could be attributed, in part, to a failure to induce
      expression of lipoprotein lipase and enzymes involved in fatty acid synthesis,
      such as fatty acid synthase and acetyl-CoA carboxylase. Related to the deficiency
      of adipose tissue, fld/fld mice were also found to exhibit profound glucose
      intolerance, modest hyperinsulinemia, and reduced tissue response to insulin. As
      insulin resistance is a important risk factor in vascular disease, we examined
      susceptibility of fld/fld mice to diet-induced atherosclerosis. Mutant mice fed
      an atherogenic diet developed 2-fold greater aortic lesions than their wild-type
      counterparts, despite having a less atherogenic lipoprotein cholesterol profile.
      The fld adipose-deficient phenotype has both similarities to and distinctions
      from the group of rare human diseases known as lipodystrophies.

PMID- 10884288
TI  - Sjogren-Larsson syndrome: accumulation of free fatty alcohols in cultured
      fibroblasts and plasma.
AB  - Sjogren-Larsson syndrome (SLS) is an inherited disorder associated with deficient
      oxidation of long-chain aliphatic alcohols. Previous studies have reported modest
      elevations in total (free + esterified) fatty alcohols in SLS, but free fatty
      alcohols have not been selectively measured, in part because of their low
      concentrations in most tissues and the presence of trace fatty alcohol
      contaminants in some solvents used for their analysis. We adapted methods to
      measure free fatty alcohols in cultured cells and plasma that minimize exogenous
      alcohol contamination. Fatty alcohols were analyzed as acetate derivatives, using
      capillary column gas chromatography. By this method, cultured skin fibroblasts
      from SLS patients were found to have 7- and 8-fold elevations in the mean content
      of hexadecanol (16:0-OH) and octadecanol (18:0-OH), respectively. The mean plasma
      16:0-OH and 18:0-OH concentrations in SLS patients (n = 11) were 9- and 22-fold
      higher than in normal controls, respectively. In SLS fibroblasts, most of the
      fatty alcohol (59%) that accumulated was free rather than esterified alcohol,
      whereas free alcohol accounted for 23% of the total alcohol in normal cells.
      These results indicate that elevations in free fatty alcohols provide a sensitive
      marker for the enzymatic defect in SLS. The ability to measure free fatty
      alcohols in cultured cells and plasma should prove useful for investigations of
      normal fatty alcohol metabolism and the deranged metabolism in SLS.

PMID- 10884289
TI  - Adenovirus-mediated gene transfer in primary murine adipocytes.
AB  - The transfer of genes into primary murine adipocytes using an adenovirus system
      has been developed. A recombinant adenovirus was constructed (expressing green
      fluorescent protein [GFP] under the control of the strong cytomegalovirus [CMV]
      promoter and a luciferase reporter gene under the control of the weak adipocyte
      promoter keratinocyte lipid-binding protein [KLBP/FABP5]) and incubated with
      primary adipocytes from C57BL/6J mice. Analysis of infected cells by confocal
      microscopy detected GFP expression in both the cytoplasm and nucleus of
      adipocytes with a 64% efficiency of infection. To demonstrate the applicability
      of this method in the study of gene regulation, adenovirus-infected adipocytes
      exhibited significant levels of luciferase activity even from a weak promoter.
      TPA treatment of infected adipocytes increased luciferase activity, consistent
      with previous studies indicating that the KLBP/FABP5 gene is up-regulated by
      phorbol esters. These results provide an efficient, convenient, and sensitive
      method to transiently infect primary murine adipocytes, facilitating protein
      expression or permitting analysis of reporter gene activity from both viral and
      endogenous promoters.

PMID- 10884290
TI  - Apolipoprotein E;-low density lipoprotein receptor interaction. Influences of
      basic residue and amphipathic alpha-helix organization in the ligand.
AB  - Conserved lysines and arginines within amino acids 140-150 of apolipoprotein
      (apo) E are crucial for the interaction between apoE and the low density
      lipoprotein receptor (LDLR). To explore the roles of amphipathic alpha-helix and
      basic residue organization in the binding process, we performed site-directed
      mutagenesis on the 22-kDa fragment of apoE (amino acids 1-191). Exchange of
      lysine and arginine at positions 143, 146, and 147 demonstrated that a positive
      charge rather than a specific basic residue is required at these positions.
      Consistent with this finding, substitution of neutral amino acids for the lysines
      at positions 143 and 146 reduced the binding affinity to about 30% of the wild
      type value. This reduction corresponds to a decrease in free energy of binding of
      approximately 600 cal/mol, consistent with the elimination of a hydrogen-bonded
      ion pair (salt bridge) between a lysine on apoE and an acidic residue on the
      LDLR. Binding activity was similarly reduced when K143 and K146 were both mutated
      to arginine (K143R + K146R), indicating that more than the side-chain positive
      charge can be important.Exchanging lysines and leucines indicated that the
      amphipathic alpha-helical structure of amino acids 140-150 is critical for normal
      binding to the low density lipoprotein receptor.

PMID- 10884291
TI  - In vivo evidence of defective postprandial and postabsorptive free fatty acid
      metabolism in familial combined hyperlipidemia.
AB  - Overproduction of very low density lipoprotein (VLDL) is the major characteristic
      of subjects with familial combined hyperlipidemia (FCHL). As enhanced free fatty
      acid (FFA) flux to the liver may be one of the determinants of VLDL
      overproduction, we studied FFA changes and products of hepatic FFA metabolism in
      response to a 24-h oral fat loading test (50 g/m(2)) in 7 FCHL subjects and 7
      matched control subjects. The response to the meal was subdivided into a
      postprandial (up to 8 h after ingestion of the meal) and postabsorptive period
      (from 8 to 24 h). Although postheparin plasma lipolytic activities were not
      different between both groups, the postprandial FFA area under the curve (FFA
      AUC) and FFA incremental area under the curve (FFA-dAUC) were higher in FCHL
      subjects than in control subjects (6.05 +/- 0.45 vs. 3.43 +/- 0.46 and 2.60 +/-
      0.49 vs. 0.96 +/- 0.31 mmol. h/L, respectively; P < 0.01 for each). The
      postprandial increase in ketone bodies was almost four times higher in FCHL
      patients. As ketogenesis occurs predominantly in hepatocytes, these findings
      suggest that during the postprandial period in FCHL an increased flux of FFA to
      the liver occurs, possibly because of inadequate incorporation of FFA into
      triglycerides (TGs) in adipocytes. In the postabsorptive period, FFA and ketone
      bodies significantly decreased in FCHL subjects, in contrast to control subjects,
      in whom both increased. These results may represent a diminished release of FFA
      from adipocytes by hormone-sensitive lipase (HSL) in FCHL patients. The decrease
      in postabsorptive FFA and ketone bodies in FCHL patients could not be explained
      by insulin-mediated inhibition of HSL, as both FCHL subjects and control subjects
      had similar postabsorptive insulin concentrations, which were below fasting
      concentrations. This study provides in vivo evidence of impaired metabolism of
      postprandial FFA in FCHL, which may explain in part the hepatic VLDL
      overproduction characteristic of FCHL subjects.

PMID- 10884292
TI  - Plasma levels of remnant particles are determined in part by variation in the
      APOC3 gene insulin response element and the APOCI-APOE cluster.
AB  - Remnant particles of triglyceride-rich lipoproteins (RLP) are known to be a
      strong predictor of atherogenicity. The serum concentrations of remnant-like
      particle triglyceride (RLPTG) and remnant-like particle cholesterol (RLPC) have
      been determined in a representative sample of the Czech MONICA study (n = 285).
      The relationship was investigated between remnant particle
      triglyceride/cholesterol concentrations and polymorphisms in the genes APOC3 (
      482C-->T/3238C-->G), APOE (epsilon2/epsilon3/epsilon4), APOCI (-317-321ins), APOB
      (signal peptide), hepatic lipase (LIPE, -480C-->T), and lipoprotein lipase (LPL,
      S447X). Univariate analysis showed significant effects on RLPTG associated only
      with the APOE genotype (P = 0.009), the APOC3 -482C-->T genotype (P = 0.018), and
      the APOCI -317-321ins (P = 0.014) genotype and significant effects on RLPC with
      APOE (P = 0.01) and APOCI -317-321ins (P = 0.021). The raising effect of the APOE
      genotype for both remnant cholesterol and triglyceride was confined to the
      epsilon2/4 (n = 6) and varepsilon4/4 (n = 3) groups, and thus when the epsilon2/4
      group was omitted in order to analyze by allele (epsilon2+/epsilon3+/epsilon4+),
      significance was lost (P = 0.6). There was strong linkage disequilibrium between
      the APOE and APOCI alleles (chi(2), P < 0.001) and a multivariate ANOVA of RLPTG
      with all three significantly associated variants as factors demonstrated that
      while the APOC3 -482C-->T effect was independent of the others (P = 0.003), the
      APOCI -317-321ins and APOE effects were not. This was also true for the APOCI 
      317-321ins and APOE effects on RLPC. To assess whether APOE-CI effects on RLPC
      were independent of their effects on total cholesterol and triglyceride levels,
      multiple linear regression was used. Using multiple linear regression, it
      appeared that the APOE-CI effects on RLPC were independent of their effects on
      plasma cholesterol, but the effects of APOC3 and APOE-CI on RLPTG could not be
      separated from their effects on plasma Tg levels. Further characterization of
      this remnant particle phenotype and its genetic determinants may lead to a better
      understanding of its metabolism and contribution to atherosclerosis.

PMID- 10884293
TI  - Sialic acid content of low density lipoprotein and its relation to lipid
      concentrations and metabolism of low density lipoprotein and cholesterol.
AB  - A low sialic acid content in low density lipoprotein (LDL) has been associated
      with atherogenicity and coronary artery disease (CAD) in many but not all
      studies. We investigated associations of the sialic acid-to-apolipoprotein B
      (apoB) ratio of LDL with lipoprotein lipid concentrations, kinetics of LDL,
      metabolism of cholesterol, and the presence of CAD in 98 subjects (CAD(+), n =
      56; CAD(-), n = 42). The sialic acid ratios of total, dense, and very dense LDL
      were lower in the CAD(+) than CAD(-) subjects, especially at high sialic acid
      ratios. The LDL sialic acid ratio was inversely associated with respective lipid
      and apoB concentrations and positively with lipid-to-apoB ratios of LDL. The
      transport rates (TRs) for total and dense LDL apoB were negatively associated
      with their sialic acid ratios. The sialic acid ratio of dense LDL, but not that
      of total LDL, was inversely correlated with serum levels of cholesterol precursor
      sterols, indicators of cholesterol synthesis, and positively with serum levels of
      plant sterols, indicators of cholesterol absorption. In addition, the TR for
      dense LDL was positively correlated with cholesterol synthesis. In conclusion, a
      low LDL sialic acid ratio was associated with CAD, high numbers of small LDL
      particles, and a high TR for LDL apoB, and in dense LDL also with high synthesis
      and low absorption of cholesterol.

PMID- 10884294
TI  - Squid nerve sphingomyelin containing an unusual sphingoid base.
AB  - A new methodology has been developed to determine sphingolipid structures by
      positive-ion fast atom bombardment tandem mass spectrometry (FAB-MS/MS). The
      method was verified by application to a structurally known glycosphingolipid, and
      then used in the structural study of an unusual sphingomyelin isolated from squid
      (Loligo pealei) nerve. Our previous study of this squid sphingomyelin indicated
      that the major base had a branched C(19) alkyl chain with three double bonds, two
      of which were conjugated. The positions of the branching as well as the double
      bonds of this base were unambiguously determined by directly comparing the
      product ion spectra of the long-chain base ion (LCB(+)) of two ceramides, one
      derived from squid nerve sphingomyelin and another, glucosylceramide, obtained
      from starfish spermatozoa. The latter served as the standard because the
      structure had already been determined by nuclear magnetic resonance (NMR). The
      precursor ion here was LCB(+), that is, [CH(2) - C(NH(2)) = CHR](+), rather than
      [M + H](+), where R represents the backbone hydrocarbon chain counting from C-4.
      The results clearly showed that the squid nerve base is identical to the base
      derived from starfish (Asterias amurensis), that is, 2-amino-9-methyl-4,8,10
      octadecatriene-1,3-diol. This is the first report in which the detailed structure
      of a branched polyunsaturated sphingoid base was studied by tandem mass
      spectrometry without derivatization or the aid of NMR. The occurrence of such an
      unusual sphingoid base in various phyla and tissues suggests the conjugated
      polyunsaturated branched sphingoid base plays a significant role in animals.

PMID- 10884295
TI  - Cellular cholesterol efflux in heterozygotes for tangier disease is markedly
      reduced and correlates with high density lipoprotein cholesterol concentration
      and particle size.
AB  - Tangier disease (TD), caused by mutations in the ATP-binding cassette 1 (ABC-1)
      gene, is a rare genetic disorder characterized by severe deficiency of high
      density lipoproteins (HDL) in the plasma, hypercatabolism of HDL, and defective
      apolipoprotein (apo)-mediated cellular cholesterol efflux. In the present study,
      we assessed plasma lipid concentrations, HDL particle size and subspecies, and
      cellular cholesterol efflux in 9 TD heterozygotes from a kindred in which the
      proband was homozygous for an A-->C missense mutation at nucleotide 5338 of the
      ABC-1 transcript. Relative to age- and gender-matched controls from the
      Framingham Offspring Study (FOS), TD heterozygotes had significant reductions (P
      < 0.000) in HDL-C (-54% female; -40% male) and apoA-I (-33% female; -37% male)
      concentrations, as well as significantly less cholesterol (-68% female; -58%
      male) distributed in the largest HDL subclasses, H5 and H4. Consequently, HDL
      particle size (nm) was significantly smaller (P < 0.000) in TD heterozygotes (8.6
      +/- 0.6 female; 8.7 +/- 0.1 male) relative to FOS controls (9.4 +/- 0.4 female;
      9.0 +/- 0.3 male). Further studies demonstrated that apoA-I-mediated cellular
      cholesterol efflux in TD heterozygotes was essentially half that of controls (11
      +/- 2 vs. 20 +/- 3% of total [(3)H]cholesterol, P < 0. 001), with strong
      correlations observed between cholesterol efflux and both HDL-C level (r = 0.600)
      and particle size (r = 0.680). In summary, our data demonstrate that
      apolipoprotein-mediated cholesterol efflux is aberrant in TD heterozygotes, as it
      is in homozygotes. This finding, along with the associations observed between HDL
      C concentration, HDL particle size, and cholesterol efflux, supports the concept
      that plasma HDL-C levels are regulated, in part, by cholesterol efflux, which in
      turn influences HDL particle size and, ultimately, HDL apoA-I catabolism.

PMID- 10884296
TI  - Effect of ER-27856, a novel squalene synthase inhibitor, on plasma cholesterol in
      rhesus monkeys: comparison with 3-hydroxy-3-methylglutaryl-coa reductase
      inhibitors.
AB  - Squalene synthase (SQS; EC 2.5.1.21) plays an important role in the cholesterol
      biosynthetic pathway. We discovered ER-28448, 5-(N-[2-butenyl-3-(2
      methoxyphenyl)]-N-methylamino)-1, 1-penthylidenebis(phosphonic acid) trisodium
      salt, as a potent and selective inhibitor of SQS. ER-28448 inhibited SQS in rat
      liver microsome with an IC(50) value of 3.6 nm. We also prepared ER-27856, the
      tripivaloyloxymethyl ester prodrug of ER-28448. Although less active than ER
      28448 in a liver microsome assay, ER-27856 more potently inhibited cholesterol
      biosynthesis in rat hepatocytes; and ER-27856 orally inhibited de novo
      cholesterol biosynthesis in Sprague-Dawley rats, with an ED(50) value of 1.6
      mg/kg. In HepG2 cells, ER-27856 upregulated low density lipoprotein receptor
      activity to 2.1 times that of control. A time-course study indicated that the
      inhibitory effect of ER-27856 on cholesterol biosynthesis in rats continued for
      up to 8 h. In a study of 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors (HMGRIs), atorvastatin actively suppressed cholesterol biosynthesis
      for 8 h, whereas the effect of pravastatin and simvastatin diminished at 4 and 8
      h, respectively. In rhesus monkeys, 4 days of oral administration of ER-27856
      lowered plasma total cholesterol (TCHO) more potently than did these HMGRIs.
      Whereas atorvastatin significantly elevated plasma alanine aminotransferase, a
      marker of hepatotoxicity, to 3.7 times at 100 mg/kg, ER-27856 increased the level
      only 1.4 times at 10 mg/kg, at which doses the hypocholesterolemic effect was
      equivalent. During 28 days of administration, ER-27856 reduced TCHO and non-high
      density lipoprotein (non-HDL) cholesterol by 72 and 95%, respectively. These
      results demonstrate that ER-27856 had more potent hypocholesterolemic activity
      and less hepatotoxic effect than HMGRIs. ER-27856 may contribute to the treatment
      of hypercholesterolemic patients.

PMID- 10884297
TI  - Increase in fragmented phosphatidylcholine in blood plasma by oxidative stress.
AB  - Oxidatively modified phospholipids with fragmented acyl chains have attracted
      much interest because of their proinflammatory activity and their potential
      involvement in atherosclerosis. They can be formed in vitro by free radical
      treatment of unsaturated phospholipids but it is not known under which conditions
      they accumulate in vivo. We assayed one species of fragmented phosphatidylcholine
      (PC) in human blood plasma by high performance liquid chromatography after
      precolumn derivatization with chloromethylanthracene. Structural analysis
      suggested that fragmented PC was a diacyl species with a palmitoyl group and a
      short oxidized residue, which most likely had four carbons. The concentration of
      fragmented PC was higher in elderly individuals with coronary heart disease than
      in young healthy controls. Smoking one cigarette acutely increased the
      concentration of fragmented PC in healthy adults. Fragmented PC also increased in
      the reperfusion period after treatment with cardiopulmonary bypass. The increase
      coincided with a surge of circulating neutrophils. In rats, the plasma
      concentration of fragmented PC was elevated by vitamin E deficiency and exposure
      to high oxygen. The data demonstrate that fragmented PC increases in blood plasma
      in response to various forms of oxidative stress.

PMID- 10884298
TI  - Subcellular organization of bile acid amidation in human liver: a key issue in
      regulating the biosynthesis of bile salts.
AB  - To extend our knowledge of how the synthesis of free bile acids and bile salts is
      regulated within the hepatocyte, bile acid-CoA:amino acid N-acyltransferase and
      bile acid-CoA thioesterase activities were measured in subcellular fractions of
      human liver homogenates. Some bile acids, both conjugated and unconjugated, have
      been reported to be natural ligands for the farnesoid X receptor (FXR), an orphan
      nuclear receptor. The conversion of [(14)C]choloyl-CoA and
      [(14)C]chenodeoxycholoyl-CoA into the corresponding tauro- and glyco-bile acids
      or the free bile acids was measured after high-pressure liquid
      radiochromatography. There was an enrichment of the N-acyltransferase in the
      cytosolic and the peroxisomal fraction. Bile acid-CoA thioesterase activities
      were enriched in the cytosolic, peroxisomal, and mitochondrial fractions. The
      highest amidation activities of both choloyl-CoA and chenodeoxycholoyl-CoA were
      found in the peroxisomal fraction (15-58 nmol/mg protein/min). The K(m) was
      higher for glycine than taurine both in cytosol and the peroxisomal
      fraction.These results show that the peroxisomal de novo synthesis of bile acids
      is rate limiting for peroxisomal amidation, and the microsomal bile acid-CoA
      synthetase is rate limiting for the cytosolic amidation. The peroxisomal location
      may explain the predominance of glyco-bile acids in human bile. Both a cytosolic
      and a peroxisomal bile acid-CoA thioesterase may influence the intracellular
      levels of free and conjugated bile acids.

PMID- 10884299
TI  - Relative importance of the LDL receptor and scavenger receptor class B in the
      beta-VLDL-induced uptake and accumulation of cholesteryl esters by peritoneal
      macrophages.
AB  - We investigated the mechanism of beta-very low density lipoprotein (beta-VLDL)
      induced foam cell formation derived from peritoneal macrophages from control mice
      and low density lipoprotein (LDL) receptor-deficient mice to elucidate the role
      of the LDL receptor in this process. The LDL receptor appeared to be of major
      importance for beta-VLDL metabolism. Consequently, the accumulation of
      cholesteryl esters in LDL receptor(-)(/)- macrophages is 2.5-fold lower than in
      LDL receptor(+)(/)(+) macrophages. In the absence of the LDL receptor, however,
      beta-VLDL was still able to induce cholesteryl ester accumulation and
      subsequently we characterized the properties of this residual beta-VLDL
      recognition site(s) of LDL receptor(-)(/)- macrophages. Although the LDL receptor
      related protein is expressed on LDL receptor(-)(/)- macrophages, the cell
      association of beta-VLDL is not influenced by the receptor-associated protein,
      and treatment of the macrophages with heparinase and chondroitinase was also
      ineffective. In contrast, both oxidized LDL (OxLDL) and anionic liposomes were
      able to inhibit the cell association of (125)I-labeled beta-VLDL in LDL receptor(
      )(/)- macrophages by 65%. These properties suggest a role for scavenger receptor
      class B (SR-B), and indeed, in the LDL receptor(-)(/)- macrophages the selective
      uptake of cholesteryl esters from beta-VLDL was 2.2-fold higher than that of
      apolipoproteins, a process that could be inhibited by OxLDL, high density
      lipoprotein (HDL), and beta-VLDL. In conclusion, the LDL receptor on peritoneal
      macrophages is directly involved in the metabolism of beta-VLDL and the
      subsequent foam cell formation. When the LDL receptor is absent, SR-B appears to
      mediate the remaining metabolism of cholesteryl esters from beta-VLDL.

PMID- 10884300
TI  - Measurement of apolipoprotein B concentration in plasma lipoproteins by combining
      selective precipitation and mass spectrometry.
AB  - The measurement of apolipoprotein B (apoB) in purified lipoproteins by
      immunological assays is subject to criticism because of denatured epitopes or
      immunoreactivity differences between purified lipoproteins and standard. Chemical
      methods have therefore been developed, such as the selective precipitation of
      apoB followed by quantification of the precipitate. In this study, we present the
      measurement of apoB concentration in lipoproteins purified by ultracentrifugation
      by combining isopropanol precipitation and gas chromatography/mass spectrometry.
      Very low density lipoprotein (VLDL; d < 1.006 g/mL); VLDL plus intermediate
      density lipoprotein (VLDL + IDL; d < 1.019 g/mL); and VLDL, IDL, and low density
      lipoprotein (VLDL + IDL + LDL; d < 1.063 g/mL) were purified by
      ultracentrifugation. Apolipoprotein B-100 was selectively precipitated by
      isopropanol. The leucine content of the pellet was then determined by gas
      chromatography/mass spectrometry, using norleucine as internal standard.
      Knowledge of the number of leucine molecules in one apoB-100 molecule makes it
      possible to calculate the plasma concentration of apoB in the various lipoprotein
      fractions. ApoB in IDL (d 1.006-1.019 g/mL) and LDL (d 1.019-1.063 g/mL) were
      then determined by subtracting VLDL-apoB from apoB in lipoproteins d < 1.019 and
      apoB in lipoproteins d < 1.019 g/mL from apoB in lipoproteins d < 1.063 g/mL,
      respectively. The isopropanol precipitate was verified as pure apoB (>97%) in
      lipoprotein fractions isolated from normo- and hyperlipidemic plasma and the
      method appeared reproducible. The combination of isopropanol precipitation and
      the GC/MS method appears therefore to be a precise and reliable method for
      kinetic and epidemiological studies.

PMID- 10884301
TI  - Single polyprenol and dolichol isolation by semipreparative high-performance
      liquid chromatography technique.
AB  - A new method of separation of single polyprenols (or dolichols) from a mixture of
      isoprenoid alcohols is described. Application of a high-performance liquid
      chromatography (HPLC) apparatus equipped with a semipreparative ODS column
      resulted in preparation of long-chain (dihydro)polyprenols of high purity (>95%).
      This approach substantially decreases the time scale of the conventional
      chromatographical preparative procedure. The method can be widely used in
      chemical and biochemical projects, where single polyprenols or dolichols are
      required.

PMID- 10884302
TI  - Elimination of the fast transient in superior cervical ganglion neurons with
      expression of KV4.2W362F: molecular dissection of IA.
AB  - Electrophysiological and molecular studies have revealed considerable
      heterogeneity in voltage-gated K(+) currents and in the subunits that underlie
      these channels in mammalian neurons. At present, however, the relationship
      between native K(+) currents and cloned subunits is poorly understood. In the
      experiments here, a molecular genetic approach was exploited to define the
      molecular correlate of the fast transient outward K(+) current, I(Af), in
      sympathetic neurons and to explore the functional role of I(Af) in shaping action
      potential waveforms and controlling repetitive firing patterns. Using the
      biolistic gene gun, cDNAs encoding a dominant negative mutant Kv4.2 alpha-subunit
      (Kv4.2W362F) and enhanced green fluorescent protein (EGFP) were introduced into
      rat sympathetic neurons in vitro. Whole-cell voltage-clamp recordings obtained
      from EGFP-positive cells revealed that I(Af) is selectively eliminated in cells
      expressing Kv4.2W362F, demonstrating that Kv4 alpha-subunits underlie I(Af) in
      sympathetic neurons. In addition, I(Af) density is increased significantly in
      cells overexpressing wild-type Kv4.2. In cells expressing Kv4.2W362F, input
      resistances are increased and (current) thresholds for action potential
      generation are decreased, demonstrating that I(Af) plays a pivotal role in
      regulating excitability. Expression of Kv4.2W362F and elimination of I(Af) also
      alters the distribution of repetitive firing patterns observed in response to a
      prolonged injection of depolarizing current. The wild-type superior cervical
      ganglion is composed of phasic, adapting, and tonic firing neurons. Elimination
      of I(Af) increases the percentage of adapting cells by shifting phasic cells to
      the adapting firing pattern, and increased I(Af) density reduces the number of
      adapting cells.

PMID- 10884303
TI  - Increased binding activity at an antioxidant-responsive element in the
      metallothionein-1 promoter and rapid induction of metallothionein-1 and -2 in
      response to cerebral ischemia and reperfusion.
AB  - Metallothioneins (MTs) are cysteine-rich metal-binding proteins that are
      potentially involved in zinc homeostasis and free radical scavenging. The
      expression pattern of MT-1 and the binding activity of various MT-1 promoter
      elements were investigated after mild focal cerebral ischemia in the rat.
      Transient focal ischemia was induced by occluding both common carotid arteries
      and the right middle cerebral artery for 30 min. By the use of real-time
      quantitative PCR, a 10-fold increase in MT-1 and -2 mRNA levels was found in the
      cortex 24 hr after reperfusion. In situ hybridization and immunocytochemistry
      showed a rapid increase in MT-1 and -2 mRNA and MT protein in endothelial cells
      of microvessels at 6 hr after reperfusion, followed by an increased expression in
      astrocytes of the infarcted cortex at 24 hr after reperfusion. The early increase
      in MT expression preceded an increase in cerebral edema measured with T2-weighted
      magnetic resonance imaging. Gel shift assays were performed on nuclear extracts
      prepared from cortices before and at 6 and 24 hr after reperfusion. Increased
      binding activity was found at an antioxidant/electrophilic response element (ARE)
      sequence in the MT-1 promoter at 6 hr with a lower and variable binding activity
      at 24 hr after reperfusion. Constitutive binding activity was found for Sp1 and a
      metal response element in the MT-1 promoter that did not increase after ischemia
      and reperfusion. This study suggests a role of ARE-binding proteins in inducing
      cerebral MT-1 expression and implicates MT-1 as one of the early detoxifying
      genes in an endogenous defense response to cerebral ischemia and reperfusion.

PMID- 10884304
TI  - Long-term potentiation of intrinsic excitability at the mossy fiber-granule cell
      synapse of rat cerebellum.
AB  - Synaptic activity can induce persistent modifications in the way a neuron reacts
      to subsequent inputs by changing either synaptic efficacy or intrinsic
      excitability. After high-frequency synaptic stimulation, long-term potentiation
      (LTP) of synaptic efficacy is commonly observed at hippocampal synapses (Bliss
      and Collingridge, 1993), and potentiation of intrinsic excitability has recently
      been reported in cerebellar deep nuclear neurons (Aizenmann and Linden, 2000).
      However, the potential coexistence of these two aspects of plasticity remained
      unclear. In this paper we have investigated the effect of high-frequency
      stimulation on synaptic transmission and intrinsic excitability at the mossy
      fiber-granule cell relay of the cerebellum. High-frequency stimulation, in
      addition to increasing synaptic conductance (D'Angelo et al., 1999), increased
      granule cell input resistance and decreased spike threshold. These changes
      depended on postsynaptic depolarization and NMDA receptor activation and were
      prevented by inhibitory synaptic activity. Potentiation of intrinsic excitability
      was induced by relatively weaker inputs than potentiation of synaptic efficacy,
      whereas with stronger inputs the two aspect of potentiation combined to enhance
      EPSPs and spike generation. Potentiation of intrinsic excitability may extend the
      computational capability of the cerebellar mossy fiber-granule cell relay.

PMID- 10884305
TI  - The regulatory connection between the activity of granule cell NMDA receptors and
      dendritic differentiation of cerebellar Purkinje cells.
AB  - It is known that cerebellar granule cells are powerful inducers for the
      differentiation of Purkinje cells. However, the detailed mechanism of this
      regulation has not yet been clarified. Here, using cerebellar neuronal culture,
      we show that the activation of NMDA receptors expressed by granule cells triggers
      the signaling pathway for the dendritic differentiation of Purkinje cells. This
      signal has been shown to promote the granule cell survival through BDNF-mediated
      TrkB activation, leading to Purkinje cell differentiation by increasing the
      granule-Purkinje cell interaction. Among the possible signal molecules provided
      to the dendrites of Purkinje cells from granule cells, nitric oxide was found to
      have no effect on the dendritic outgrowth and branching, but electrical activity
      and the subsequent intracellular Ca(2+) increase were thought to play an
      important role in the branching and thickening of the dendrites, because blockade
      of both non-NMDA and metabotropic glutamate receptors caused a significant
      decrease in the number of branch points and the diameter of Purkinje dendrites
      without apparently affecting the dendrite extension and spine formation.
      Collectively, these results suggest that Purkinje cell differentiation is
      regulated by two successive steps. The first step is initiated by the NMDA
      receptor-mediated signal in granule cells, which acts as a trophic factor for
      granule cells. The second step involves the activation of granule-Purkinje
      synapses, providing neurotrophic substances and electrical activity essential for
      Purkinje cell differentiation.

PMID- 10884306
TI  - Early onset of axonal degeneration in double (plp-/-mag-/-) and hypomyelinosis in
      triple (plp-/-mbp-/-mag-/-) mutant mice.
AB  - Double (plp-/-mag-/-) and triple (plp-/-mbp-/-mag-/-) null-allelic mouse lines
      deficient in proteolipid protein (PLP), myelin-associated glycoprotein (MAG), and
      myelin basic protein (MBP) were generated and characterized genetically,
      biochemically, and morphologically including their behavioral capacities. The plp
      /-mag-/- mutant develops a rapidly progressing axon degeneration in CNS with
      severe cognitive and motor coordinative deficits but has a normal longevity. CNS
      axons of the plp-/-mbp-/-mag-/- mouse are hypomyelinated and ensheathed by
      "pseudomyelin" with disturbed protein and complex lipid composition. The shiverer
      trait in the plp-/-mbp-/-mag-/- similar to the plp-/-mbp-/- mutant is
      significantly ameliorated, and its lifespan is considerably prolonged. The
      longevity of these dysmyelinosis mouse mutants recommends them as suitable models
      for the long-term evaluation of stem cell therapeutic strategies.

PMID- 10884307
TI  - Mice deficient in the polysialyltransferase ST8SiaIV/PST-1 allow discrimination
      of the roles of neural cell adhesion molecule protein and polysialic acid in
      neural development and synaptic plasticity.
AB  - Functional properties of the neural cell adhesion molecule (NCAM) are strongly
      influenced by polysialylation. We used gene-targeting to generate mice lacking
      ST8SiaIV/PST-1, one of the polysialyltransferases responsible for addition of
      polysialic acid (PSA) to NCAM. Mice homozygous for the null mutation reveal
      normal development of gross anatomical features. In contrast to NCAM-deficient
      mice, olfactory precursor cells in the rostral migratory stream express PSA and
      follow their normal pathway. Furthermore, delamination of mossy fibers in the
      hippocampal CA3 region, as found in NCAM-deficient mice, does not occur in
      ST8SiaIV mutants. However, during postnatal development these animals show a
      decrease of PSA in most brain regions compared to wild-type animals. Loss of PSA
      in the presence of NCAM protein but in the absence of obvious histological
      changes allowed us to directly address the role of PSA in synaptic plasticity.
      Schaffer collateral-CA1 synapses, which express PSA in wild types, showed
      impaired long-term potentiation (LTP) and long-term depression (LTD) in adult
      mutants. This impairment was age-dependent, following the time course of
      developmental disappearance of PSA. Contrary to NCAM mutant mice, LTP in ST8SiaIV
      mutants was undisturbed at mossy fiber-CA3 synapses, which do not express PSA in
      wild-type mice. The results demonstrate an essential role for ST8SiaIV in
      synaptic plasticity in hippocampal CA1 synapses, whereas PSA produced by
      different polysialyltransferase or polysialyltransferases at early stages of
      differentiation regulates migration of neural precursor cells and correct
      lamination of mossy fibers. We suggest that NCAM but not PSA is likely to be
      important for LTP in the hippocampal CA3 region.

PMID- 10884308
TI  - Modulation of Kv1.5 currents by Src tyrosine phosphorylation: potential role in
      the differentiation of astrocytes.
AB  - Using biophysical techniques, we previously have implicated outwardly rectifying
      potassium currents in the proliferation of cultured spinal cord astrocytes and
      have demonstrated that delayed rectifier potassium currents (I(Kd)), in
      particular, are upregulated on entry into the cell cycle and downregulated with
      cell cycle exit and differentiation. In the present study, using specific
      antibodies and antisense oligodeoxynucleotides, we show that this proliferation
      dependent potassium current is mediated by the Shaker potassium channel Kv1.5.
      Downregulation of Kv1.5 protein by antisense oligodeoxynucleotides reduces
      astrocyte proliferation by approximately 50%, although no observed changes occur
      in Kv1.5 protein expression during spontaneous differentiation in culture.
      Tyrosine phosphorylation of Kv1.5, however, is downregulated markedly in
      differentiated cells but unaltered on cell cycle arrest. Using
      immunoprecipitation, we show that Kv1.5 is associated with Src family protein
      tyrosine kinases and that this association does not change with cell
      differentiation. Inhibition of kinase activity with the Src-specific inhibitor
      PP2 decreases Kv1.5 phosphorylation, reduces I(Kd), and inhibits astrocyte
      proliferation, specifically in the G(0)/G(1) phase of cell cycle. Conversely,
      I(Kd) are potentiated when active Src is present in the pipette. Transfection of
      quiescent astrocytes with constitutively active Src (Src Y529F) causes marked
      upregulation of astrocyte proliferation. These data suggest that Kv1. 5 is
      phosphorylated constitutively by Src kinases during growth and that
      downregulation of Src activity may underlie both astrocyte differentiation and
      the accompanying changes in delayed rectifier potassium channel activity.

PMID- 10884309
TI  - Light transduction in invertebrate hyperpolarizing photoreceptors: possible
      involvement of a Go-regulated guanylate cyclase.
AB  - The hyperpolarizing receptor potential of scallop ciliary photoreceptors is
      attributable to light-induced opening of K(+)-selective channels. Having
      previously demonstrated the activation of this K(+) current by cGMP, we examined
      upstream events in the transduction cascade. GTP-gamma-S produced persistent
      excitation after a flash, accompanied by decreased sensitivity and acceleration
      of the photocurrent, whereas GDP-beta-S only inhibited responsiveness, consistent
      with the involvement of a G-protein. Because G(o) (but not G(t) nor G(q))
      recently has been detected in the ciliary retinal layer of a related species, we
      tested the effects of activators of G(o); mastoparan peptides induced an outward
      current suppressible by blockers of the light-sensitive conductance such as l-cis
      diltiazem. In addition, intracellular dialysis with the A-protomer of pertussis
      toxin (PTX) depressed the photocurrent. The mechanisms that couple G-protein
      stimulation to changes in cGMP were investigated. Intracellular IBMX enhanced the
      photoresponse with little effect on the baseline current, a result that argues
      against regulation by light of phosphodiesterase activity. LY83583, an inhibitor
      of guanylate cyclase (GC), exerted a reversible, dose-dependent suppression of
      the photocurrent. By contrast, ODQ, an antagonist of NO-sensitive GC, and YC-1,
      an activator of NO-sensitive GC, failed to alter the light response or the
      holding current; furthermore, the NO synthase inhibitor N-methyl- l-arginine was
      inert, indicating that the NO signaling pathway is not implicated. Taken
      together, these results suggest a novel type of phototransduction cascade in
      which stimulation of a PTX-sensitive G(o) may activate a membrane GC to induce an
      increase in cGMP and the consequent opening of light-dependent channels.

PMID- 10884310
TI  - Molecular and functional heterogeneity of hyperpolarization-activated pacemaker
      channels in the mouse CNS.
AB  - The hyperpolarization-activated cation current (termed I(h), I(q), or I(f)) was
      recently shown to be encoded by a new family of genes, named HCN for
      hyperpolarization-activated cyclic nucleotide-sensitive cation nonselective. When
      expressed in heterologous cells, each HCN isoform generates channels with
      distinct activation kinetics, mirroring the range of biophysical properties of
      native I(h) currents recorded in different classes of neurons. To determine
      whether the functional diversity of I(h) currents is attributable to different
      patterns of HCN gene expression, we determined the mRNA distribution across
      different regions of the mouse CNS of the three mouse HCN genes that are
      prominently expressed there (mHCN1, 2 and 4). We observe distinct patterns of
      distribution for each of the three genes. Whereas mHCN2 shows a widespread
      expression throughout the CNS, the expression of mHCN1 and mHCN4 is more limited,
      and generally complementary. mHCN1 is primarily expressed within neurons of the
      neocortex, hippocampus, and cerebellar cortex, but also in selected nuclei of the
      brainstem. mHCN4 is most highly expressed within neurons of the medial habenula,
      thalamus, and olfactory bulb, but also in distinct neuronal populations of the
      basal ganglia. Based on a comparison of mRNA expression with an
      electrophysiological characterization of native I(h) currents in hippocampal and
      thalamic neurons, our data support the idea that the functional heterogeneity of
      I(h) channels is attributable, in part, to differential isoform expression.
      Moreover, in some neurons, specific functional roles can be proposed for I(h)
      channels with defined subunit composition.

PMID- 10884311
TI  - VMAT-Mediated changes in quantal size and vesicular volume.
AB  - It has been well established that the volume of secretory vesicles can be
      modulated. However, we present the first data demonstrating that the amount of
      transmitter in a vesicle can regulate its volume. Amperometry and transmission
      electron microscopy have been used to determine that l-3,4-dihydroxyphenylalanine
      and reserpine increase and decrease, respectively, the volume of single
      pheochromocytoma cell vesicles as well as their catecholamine content. Because
      changes in vesicular catecholamine content are tracked by changes in vesicle
      volume, our results indicate that when quantal size is altered via the vesicular
      monoamine transporter the concentration of catecholamines within the vesicles
      remains relatively constant. This previously unidentified cellular response
      provides new insight into how catecholamines can be packaged in and released from
      secretory vesicles.

PMID- 10884312
TI  - Neuroprotection by encephalomyelitis: rescue of mechanically injured neurons and
      neurotrophin production by CNS-infiltrating T and natural killer cells.
AB  - In experimental autoimmune encephalomyelitis (EAE), CD4(+) self-reactive T cells
      target myelin components of the CNS. However, the consequences of an
      autoaggressive T cell response against myelin for neurons are currently unknown.
      We herein demonstrate that EAE induced by active immunization with an
      encephalitogenic myelin basic protein peptide dramatically reduces the loss of
      spinal motoneurons after ventral root avulsion in rats. Both brain-derived
      neurotophic factor (BDNF)- and neurotrophin-3 (NT-3)-like immunoreactivities were
      detected in mainly T and natural killer (NK) cells in the spinal cord. In
      addition, very high levels of BDNF, NT-3, and glial cell line-derived
      neurotrophic factor mRNAs were present in T and NK cell populations infiltrating
      the CNS. Interestingly, bystander recruited NK and T cells displayed similar or
      higher neurotrophic factor levels compared with the EAE disease-driving
      encephalitogenic T cell population. High levels of tumor necrosis factor-alpha
      (TNF-alpha) and interferon-gamma (IFN-gamma) mRNAs were also detected, and both
      these cytokines can be harmful to several types of CNS cells, including neurons.
      However, treatment of embryonic motoneuron cultures with TNF-alpha or IFN-gamma
      only had a deleterious effect in cultures deprived of neurotrophic factors. These
      results suggest that the potentially neurodamaging consequences of severe CNS
      inflammation are curbed by the production of several potent neurotrophic factors
      in leukocytes.

PMID- 10884313
TI  - Modulation of interleukin-1beta and tumor necrosis factor alpha signaling by P2
      purinergic receptors in human fetal astrocytes.
AB  - In human astrocytes, interleukin-1beta (IL-1beta) is a potent inducer of genes
      associated with inflammation. In this study, we tested the hypothesis that in
      primary cultures of human fetal astrocytes signaling by the P2 purinergic
      nucleotide receptor pathway contributes to, or modulates, cytokine-mediated
      signal transduction. Calcium imaging studies indicated that most cells in culture
      responded to ATP, whereas only a subpopulation responded to UTP. Pretreatment of
      astrocytes with P2 receptor antagonists, including suramin and periodate oxidized
      ATP (oATP), resulted in a significant downregulation of IL-1beta-stimulated
      expression of nitric oxide, tumor necrosis factor (TNFalpha), and IL-6 at both
      the protein and mRNA levels, without affecting cell viability. In cells
      transiently transfected with reporter constructs, IL-1beta demonstrated more
      potent activation of the transcription factors nuclear factor -kappaB (NF-kappaB)
      and activator protein-1 (AP-1) than TNFalpha. However, pretreatment with oATP
      downregulated activation of NF-kappaB and AP-1 by IL-1beta or TNFalpha.
      Electromobility shift assays using oligonucleotides containing specific NF-kappaB
      binding sequences confirmed that pretreatment with oATP or apyrase attenuated
      cytokine-mediated induction of this transcription factor. From these data, we
      conclude that P2 receptor-mediated signaling intersects with that of IL-1beta and
      TNFalpha to regulate responses to cytokines in the CNS. Because inflammation,
      trauma, and stress all lead to the release of high levels of extracellular
      nucleotides, such as ATP and UTP, signaling via P2 receptors may provide a
      mechanism whereby cells can sense and respond to events occurring in the
      extracellular environment and can fine tune the transcription of genes involved
      in the inflammatory response.

PMID- 10884314
TI  - Columnar organization of dendrites and axons of single and synaptically coupled
      excitatory spiny neurons in layer 4 of the rat barrel cortex.
AB  - Cortical columns are the functional units of the neocortex that are particularly
      prominent in the "barrel" field of the somatosensory cortex. Here we describe the
      morphology of two classes of synaptically coupled excitatory neurons in layer 4
      of the barrel cortex, spiny stellate, and star pyramidal cells, respectively.
      Within a single barrel, their somata tend to be organized in clusters. The
      dendritic arbors are largely confined to layer 4, except for the distal part of
      the apical dendrite of star pyramidal neurons that extends into layer 2/3. In
      contrast, the axon of both types of neurons spans the cortex from layer 1 to
      layer 6. The most prominent axonal projections are those to layers 4 and 2/3
      where they are largely restricted to a single cortical column. In layers 5 and 6,
      a small fraction of axon collaterals projects also across cortical columns.
      Consistent with the dense axonal projection to layers 4 and 2/3, the total number
      and density of boutons per unit axonal length was also highest there. Electron
      microscopy combined with GABA postimmunogold labeling revealed that most (>90%)
      of the synaptic contacts were established on dendritic spines and shafts of
      excitatory neurons in layers 4 and 2/3. The largely columnar organization of
      dendrites and axons of both cell types, combined with the preferential and dense
      projections within cortical layers 4 and 2/3, suggests that spiny stellate and
      star pyramidal neurons of layer 4 serve to amplify thalamic input and relay
      excitation vertically within a single cortical column.

PMID- 10884315
TI  - Properties and plasticity of paired-pulse depression at a central synapse.
AB  - Synaptic depression was studied at the axo-axonic connection between the goldfish
      Mauthner axon and identified cranial relay interneurons using simultaneous
      presynaptic and postsynaptic recordings and a paired-pulse stimulus paradigm. We
      used interstimulus intervals (ISIs) ranging from 10 msec to 1 sec and a cycle
      time of approximately 5 sec. Depression (Delta EPSP/EPSP1) was maximal at the
      shorter intervals (80%) and decreased exponentially with a tau approximately 400
      msec (360 +/- 107 msec, mean +/- SD). We found the amplitudes of the first and
      second EPSP were not correlated, indicating the magnitude of depression does not
      depend on the amount of transmitter released by the conditioning stimulus. At
      short ISIs, the latency of EPSP2 was 23% longer than that of EPSP1 and recovered
      to control with tau approximately 400 msec, whereas rise time and decay time were
      not altered significantly. The latency distribution, which is determined by the
      timing of the first quantum released each trial, was used to derive alpha(t), the
      rate of evoked exocytosis after an action potential. alpha(t) was biphasic, and
      both components were consistently delayed during depression. Presynaptic
      manipulations of putative intracellular regulatory pathways, such as Ca(2+) and
      GTPgammaS injections, preferentially affected the amplitude of EPSP1 or EPSP2.
      These results are not consistent with simple depletion of the available pool of
      synaptic vesicles as the major mechanism underlying depression. They rather
      suggest that it is attributable to a modification or refractoriness of the
      release process and that there may be multiple pathways subserving evoked
      exocytosis.

PMID- 10884316
TI  - Formation of intermediate filament protein aggregates with disparate effects in
      two transgenic mouse models lacking the neurofilament light subunit.
AB  - Protein aggregates containing intermediate filaments (IFs) are a hallmark of
      degenerating spinal motor neurons in amyotrophic lateral sclerosis (ALS).
      Recently, we reported that a deficiency in neurofilament light subunit (NF-L), a
      phenomenon associated with ALS, promoted the formation of IF inclusions with
      ensuing motor neuron death in transgenic mice overproducing peripherin, a type
      III IF protein detected in axonal inclusions of ALS patients. To further assess
      the role of NF-L in the formation of abnormal IF inclusions, we generated
      transgenic mice overexpressing human neurofilament heavy subunits (hNF-H) in a
      context of targeted disruption of the NF-L gene (hH;L-/- mice). The hH;L-/- mice
      exhibited motor dysfunction, and they developed nonfilamentous protein aggregates
      containing NF-H and peripherin proteins in the perikarya of spinal motor neurons.
      However, the perikaryal protein aggregates in the hH;L-/- mice did not provoke
      motor neuron death, unlike toxic IF inclusions induced by peripherin
      overexpression in NF-L null mice (Per;L-/- mice). Our results indicate that
      different types of IF protein aggregates with distinct properties may occur in a
      context of NF-L deficiency and that an axonal localization of such aggregates may
      be an important factor of toxicity.

PMID- 10884317
TI  - Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in
      hippocampal pyramidal neurons.
AB  - The shape of dendritic trees and the density of dendritic spines can undergo
      significant changes during the life of a neuron. We report here the function of
      the small GTPases Rac and Rho in the maintenance of dendritic structures.
      Maturing pyramidal neurons in rat hippocampal slice culture were biolistically
      transfected with dominant GTPase mutants. We found that expression of dominant
      negative Rac1 results in a progressive elimination of dendritic spines, whereas
      hyperactivation of RhoA causes a drastic simplification of dendritic branch
      patterns that is dependent on the activity of a downstream kinase ROCK. Our
      results suggest that Rac and Rho play distinct functions in regulating dendritic
      spines and branches and are vital for the maintenance and reorganization of
      dendritic structures in maturing neurons.

PMID- 10884318
TI  - Bax inactivation in lurcher mutants rescues cerebellar granule cells but not
      purkinje cells or inferior olivary neurons.
AB  - Lurcher is a gain-of-function mutation in the delta2 glutamate receptor gene
      (Grid2) that turns the receptor into a leaky ion channel. The expression of the
      Lurcher gene in heterozygous (Grid2(Lc/+)) mutants induces the death of almost
      all Purkinje cells starting from the second postnatal week. Ninety percent of the
      granule cells and 60-75% of the inferior olivary neurons die because of the loss
      of their target neurons, the Purkinje cells. The apoptotic nature of the
      neurodegeneration has been demonstrated previously by the presence of activated
      caspase-3 and DNA fragmentation. Bax, a pro-apoptotic gene of the Bcl-2 family,
      has been shown to be involved in developmental neuronal death. To study the role
      of Bax in Grid2(Lc/+) neurodegeneration, double mutants with Grid2(Lc/)+ mice and
      Bax knock-out mice (Bax-/-) were generated. Bax deletion had no effect on the
      death of Purkinje cells and inferior olivary neurons, although a temporary rescue
      of some Purkinje cells could be detected in P15 Grid2(Lc/)+;Bax-/- animals. From
      postnatal day 15 (P15) to P60, the number of granule cells in Grid2(Lc/)+;Bax-/
      mice did not significantly change and was significantly increased compared with
      the number found in Grid2(Lc/)+;Bax+/+ mice. Granule cell number in P60
      Grid2(Lc/)+;Bax-/- mice corresponded to 70% of the number found in wild-type
      mice. Our results show that Bax inactivation in Grid2(Lc/+) mice does not rescue
      intrinsic Purkinje cell death or the target-related cell death of olivary
      neurons, but Bax inactivation does inhibit persistently target-related cell death
      in cerebellar granule cells.

PMID- 10884320
TI  - The "waiting period" of sensory and motor axons in early chick hindlimb: its role
      in axon pathfinding and neuronal maturation.
AB  - During embryonic development motor axons in the chick hindlimb grow out slightly
      before sensory axons and wait in the plexus region at the base of the limb for
      approximately 24 hr before invading the limb itself (Tosney and Landmesser,
      1985a). We have investigated the role of this waiting period by asking, Is the
      arrest of growth cones in the plexus region a general property of both sensory
      and motor axons? Why do axons wait? Does eliminating the waiting period affect
      the further development of motor and sensory neurons? Here we show that sensory
      axons, like motor axons, pause in the plexus region and that neither sensory nor
      motor axons require cues from the other population to wait in or exit from the
      plexus region. By transplanting older or younger donor limbs to host embryos, we
      show that host axons innervate donor limbs on a schedule consistent with the age
      of the grafted limbs. Thus, axons wait in the plexus region for maturational
      changes to occur in the limb rather than in the neurons themselves. Both sensory
      and motor axons innervate their appropriate peripheral targets when the waiting
      period is eliminated by grafting older donor limbs. Therefore, axons do not
      require a prolonged period in the plexus region to sort out and project
      appropriately. Eliminating the waiting period does, however, accelerate the onset
      of naturally occurring cell death, but it does not enhance the development of
      central projections or the biochemical maturation of sensory neurons.

PMID- 10884321
TI  - TrkB receptor ligands promote activity-dependent inhibitory synaptogenesis.
AB  - Organotypic cerebellar cultures derived from newborn mice were simultaneously
      exposed to activity-blocking agents and neurotrophins for 2 weeks. Activity
      blocked explants treated with the TrkB receptor ligands BDNF and neurotrophin-4
      (NT-4) developed a full complement of Purkinje cell inhibitory axosomatic
      synapses, as defined ultrastructurally, and displayed control spontaneous
      cortical discharge rates after recovery from activity blockade. Otherwise
      untreated activity-blocked cultures and activity-blocked cultures exposed to the
      TrkC receptor ligand NT-3 had reduced inhibitory synapse development and
      persistent cortical hyperactivity after recovery. The added TrkB receptor ligands
      did not induce axonal sprouting to account for increased inhibitory
      synaptogenesis. Addition of neurotrophins to untreated cerebellar cultures did
      not increase the complement of Purkinje cell axosomatic synapses. Exposure of
      cerebellar cultures to a combination of antibodies to BDNF and NT-4 resulted in
      reduced inhibitory synapse formation, similar to the effects of activity
      blockade, indicating the necessity for endogenous neurotrophins for development
      of the full complement of inhibitory synapses in the presence of neuronal
      activity. Application of antibodies to BDNF and NT-4 to cerebellar explants
      exposed to picrotoxin to increase neuronal activity prevented the
      hyperinnervation of Purkinje cell somata by inhibitory terminals characteristic
      of cultures exposed to picrotoxin alone. These results are consistent with the
      concept that TrkB receptor ligands promote inhibitory synaptogenesis. The ability
      of neurotrophins to substitute for neuronal activity in encouraging development
      of inhibitory synapses may have therapeutic implications.

PMID- 10884319
TI  - Activity-dependent regulation of substance P expression and topographic map
      maintenance by a cholinergic pathway.
AB  - We have assessed the role of activity in the adult frog visual system in
      modulating two aspects of neuronal plasticity: neurotransmitter expression and
      topographic map maintenance. Chronic treatment of one tectal lobe with the non
      NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione decreased the
      percentage of substance P-like immunoreactive (SP-IR) tectal cells in the
      untreated lobe while disrupting topographic map formation in the treated one.
      Treatment with the NMDA receptor antagonist d-(-)-2-amino-5-phosphonovaleric acid
      (d-AP-5) disrupted the topographic map but had no affect on SP-IR cells. These
      results indicate that maintenance of the topographic map is dependent on direct
      input from the glutamatergic retinal ganglion cells, whereas substance P (SP)
      expression is being regulated by a pathway that relays activity from one tectal
      lobe to the other. Such a pathway is provided by the cholinergic nucleus isthmi,
      which is reciprocally connected to the ipsilateral tectum and sends a projection
      to the contralateral one. Mecamylamine and atropine, antagonists of nicotinic and
      muscarinic receptors, respectively, were used together to block all cholinergic
      activity or alone to block receptor subclass activity. All three treatments
      decreased SP expression and disrupted the topographic map in the treated tectal
      lobe. We conclude that both SP expression and topographic map maintenance in the
      adult optic tectum are activity-dependent processes. Although our results are
      consistent with the maintenance of the topographic map through an NMDA receptor
      based mechanism, they suggest that SP expression is regulated by a cholinergic
      interaction that depends on retinal ganglion cell input only for its activation.

PMID- 10884322
TI  - GABA in the deep layers of the superior Colliculus/Mesencephalic reticular
      formation mediates the enhancement of startle by the dopamine D1 receptor agonist
      SKF 82958 in rats.
AB  - GABA transmission in the deep layers of the superior colliculus/deep
      mesencephalic reticular formation (deep SC/Me) mediates several motor responses,
      including those expressed after systemic administration of dopamine agonists. In
      the present study we examined the role of the deep SC/Me in the modulation of the
      acoustic startle reflex and its enhancement by the dopamine D(1) agonist SKF
      82958. Rats were implanted with bilateral cannulas into the deep SC/Me or
      superficial layers of the SC (super SC) and 1 week later were infused with
      various compounds. The GABA(A) antagonist bicuculline (0, 5, and 10 ng) produced
      a dose- and time-dependent enhancement of startle after infusion into the deep
      SC/Me, but not the super SC. Infusion of the GABA(A) agonist muscimol (0.1
      microg) into the deep SC/Me, but not the super SC, blocked the enhancement of
      startle by systemic SKF 82958 (1 mg/kg) but had no effect on baseline startle by
      itself. This effect was not produced by infusion of the D(1) antagonist SCH
      23390(1 microg) or the glutamate antagonist NBQX (0.1 microg). Deposits of
      FluoroGold into the deep SC/Me, combined with immunohistochemistry for glutamic
      acid decarboxylase (GAD), confirmed a direct GABAergic input from the substantia
      nigra pars reticulata (SNr) to the deep SC/Me. These results suggest that GABA
      tone in the deep SC/Me modulates the expression of startle as well as the
      enhancement of startle by dopamine D(1) agonists. On the basis of these data and
      previous work, we have proposed a striatonigral-tectal-reticular neural pathway
      mediating the effects of dopamine D(1) agonists on startle.

PMID- 10884323
TI  - Interaction between metabotropic and ionotropic glutamate receptors regulates
      neuronal network activity.
AB  - Experimental and computational techniques have been used to investigate the group
      I metabotropic glutamate receptor (mGluR)-mediated increase in the frequency of
      spinal cord network activity underlying locomotion in the lamprey. Group I mGluR
      activation potentiated the amplitude of NMDA-induced currents in identified
      motoneurons and crossed caudally projecting network interneurons. Group I mGluRs
      also potentiated NMDA-induced calcium responses. This effect was blocked by a
      group I mGluR-specific antagonist, but not by blockers of protein kinase A, C, or
      G. The effect of group I mGluRs activation was also tested on NMDA-induced
      oscillations known to occur during fictive locomotion. Activation of these
      receptors increased the duration of the plateau phase and decreased the duration
      of the hyperpolarizing phase. These effects were blocked by a group I mGluR
      antagonist. To determine its role in the modulation of NMDA-induced oscillations
      and the locomotor burst frequency, the potentiation of NMDA receptors by mGluRs
      was simulated using computational techniques. Simulating the interaction between
      these receptors reproduced the modulation of the plateau and hyperpolarized
      phases of NMDA-induced oscillations, and the increase in the frequency of the
      locomotor rhythm. Our results thus show a postsynaptic interaction between group
      I mGluRs and NMDA receptors in lamprey spinal cord neurons, which can account for
      the regulation of the locomotor network output by mGluRs.

PMID- 10884324
TI  - Temporal coding of visual information in the thalamus.
AB  - The amount of information a sensory neuron carries about a stimulus is directly
      related to response reliability. We recorded from individual neurons in the cat
      lateral geniculate nucleus (LGN) while presenting randomly modulated visual
      stimuli. The responses to repeated stimuli were reproducible, whereas the
      responses evoked by nonrepeated stimuli drawn from the same ensemble were
      variable. Stimulus-dependent information was quantified directly from the
      difference in entropy of these neural responses. We show that a single LGN cell
      can encode much more visual information than had been demonstrated previously,
      ranging from 15 to 102 bits/sec across our sample of cells. Information rate was
      correlated with the firing rate of the cell, for a consistent rate of 3.6 +/- 0.6
      bits/spike (mean +/- SD). This information can primarily be attributed to the
      high temporal precision with which firing probability is modulated; many
      individual spikes were timed with better than 1 msec precision. We introduce a
      way to estimate the amount of information encoded in temporal patterns of firing,
      as distinct from the information in the time varying firing rate at any temporal
      resolution. Using this method, we find that temporal patterns sometimes introduce
      redundancy but often encode visual information. The contribution of temporal
      patterns ranged from -3.4 to +25.5 bits/sec or from -9.4 to +24.9% of the total
      information content of the responses.

PMID- 10884325
TI  - Selective alterations in GABAA receptor subtypes in human temporal lobe epilepsy.
AB  - Temporal lobe epilepsy (TLE) is associated with impaired inhibitory
      neurotransmission. Studies in animal models suggest that GABA(A) receptor
      dysfunction contributes to epileptogenesis. To understand the mechanisms
      underlying TLE in humans, it is fundamental to determine whether and how GABA(A)
      receptor subtypes are altered. Furthermore, identifying novel receptor targets is
      a prerequisite for developing selective antiepileptic drugs. We have therefore
      analyzed subunit composition and distribution of the three major GABA(A) receptor
      subtypes immunohistochemically with subunit-specific antibodies (alpha1, alpha2,
      alpha3, beta2,3, and gamma2) in surgical specimens from TLE patients with
      hippocampal sclerosis (n = 16). Profound alterations in GABA(A) receptor subtype
      expression were observed when compared with control hippocampi (n = 10). Although
      decreased GABA(A) receptor subunit staining, reflecting cell loss, was observed
      in CA1, CA3, and hilus, the distinct neuron-specific expression pattern of the
      alpha-subunit variants observed in controls was markedly changed in surviving
      neurons. In granule cells, prominent upregulation mainly of the alpha2-subunit
      was seen on somata and apical dendrites with reduced labeling on basal dendrites.
      In CA2, differential rearrangement of all three alpha-subunits occurred.
      Moreover, there was layer-specific loss of alpha1-subunit-immunoreactive
      interneurons in hippocampus proper, whereas surviving interneurons exhibited
      extensive changes in dendritic morphology. Throughout, expression patterns of
      beta2,3- and gamma2-subunits largely followed those of alpha-subunit variants.
      These results demonstrate unique subtype-specific expression of GABA(A) receptors
      in human hippocampus. The significant reorganization of distinct receptor
      subtypes in surviving hippocampal neurons of TLE patients with hippocampal
      sclerosis underlines the potential for synaptic plasticity in the human GABA
      system.

PMID- 10884326
TI  - Different subthreshold mechanisms underlie song selectivity in identified HVc
      neurons of the zebra finch.
AB  - Songbirds learn and maintain their songs via auditory experience. Neurons in many
      telencephalic nuclei important to song production and development are song
      selective, firing more to forward auditory playback of the bird's own song (BOS)
      than to reverse BOS or conspecific songs. Elucidating circuits that generate
      these responses can localize where auditory experience influences vocalization,
      bridging cellular and systems analyses of song learning. Song-selective responses
      in many song nuclei, including the vocal premotor nucleus robustus
      archistriatalis (RA) and the basal ganglia homolog area X, are thought to
      originate in nucleus HVc (used as a proper name), which contains interneurons and
      relay cells that innervate either RA or area X. Previous studies indicated that
      only X-projecting neurons have auditory responses, leaving open the source of
      RA's auditory input and the degree to which song selectivity may be refined in
      HVc. Here, in vivo intracellular recordings from morphologically and
      electrophysiologically identified HVc neurons revealed that both relay cell types
      fire song-selectively. However, their firing arises via markedly different
      subthreshold processes, and only X-projecting neurons appear to be sites for
      auditory refinement. RA-projecting neurons exhibited purely depolarizing
      subthreshold responses that were highly song selective and that were excitatory.
      In contrast, subthreshold responses of X-projecting neurons included less
      selective depolarizing and highly selective hyperpolarizing components. Within
      individual birds, these BOS-evoked hyperpolarizations closely matched
      interneuronal firing, suggesting that HVc interneurons make restricted inputs
      onto X-projecting neurons. Because of the two relay cell types' subthreshold
      differences, factors affecting their resting membrane potentials could enable
      them to transmit distinct song representations to their targets.

PMID- 10884327
TI  - Intrinsic and extrinsic contributions to auditory selectivity in a song nucleus
      critical for vocal plasticity.
AB  - The development, maintenance, and perception of learned vocalizations in
      songbirds are likely to require auditory neurons that respond selectively to
      song. Neurons with song-selective responses have been described in several brain
      nuclei critical to singing, but the mechanisms by which such response properties
      arise, are modified, and propagate are poorly understood. The lateral
      magnocellular nucleus of the anterior neostriatum (LMAN) is the output of an
      anterior forebrain pathway (AFP) essential for learning and maintenance of song,
      processes dependent on auditory feedback. Although neurons throughout this
      pathway respond selectively to auditory presentation of the bird's own song, LMAN
      is the last stage at which responses to this auditory information could be
      transformed before being transmitted to vocal motor areas, where such responses
      may influence vocal production. Indeed, previous extracellular studies have
      indicated that LMAN's auditory selectivity is greater than that at earlier stages
      of the AFP. To determine whether LMAN local circuitry transforms or simply relays
      song-related auditory information to vocal control neurons, it is essential to
      distinguish local from extrinsic contributions to LMAN's auditory selectivity. In
      vivo intracellular recordings from LMAN projection neurons, coupled with local
      circuit inactivation, reveal that much of LMAN's song selectivity is supplied by
      its extrinsic inputs, but selective blockade of GABA receptors indicates that
      local inhibition is required for the expression of song selectivity. Therefore,
      LMAN neurons receive highly song-selective information, but LMAN's local
      circuitry can mask these selective inputs, providing a mechanism for context
      dependent auditory feedback.

PMID- 10884328
TI  - Regulation of rat cortex function by D1 dopamine receptors in the striatum.
AB  - Interactions between the basal ganglia and the cerebral cortex are critical for
      normal goal-directed behavior. In the present study, we used immediate-early
      genes (c-fos, zif 268) as functional markers to investigated how basal ganglia
      output altered by stimulation/blockade of D1 dopamine receptors in the striatum
      affects cortical function. Systemic administration of the mixed D1/D2 receptor
      agonist apomorphine (3 mg/kg) increased immediate-early gene expression in the
      striatum and throughout most of the cortex. Unilateral intrastriatal infusion of
      the selective D1 receptor antagonist SCH-23390 (0.5-10 microg) blocked this
      response bilaterally in striatum and cortex in a dose-dependent manner. Even
      apparently regionally restricted blockade of striatal D1 receptors attenuated
      gene expression throughout striatum and cortex in both hemispheres. Intrastriatal
      administration of the D1 antagonist inhibited apomorphine-induced
      sniffing/whisking, whereas other motor behaviors were unaffected. To determine
      whether such changes in cortical gene expression could reflect altered cortical
      function, we examined the effects of blocking striatal D1 receptors on whisker
      stimulation-evoked immediate-early gene expression in the sensorimotor cortex.
      Apomorphine increased sensory stimulation-evoked gene expression in the barrel
      cortex, and intrastriatal infusion of SCH-23390 attenuated this effect. These
      results suggest that stimulation of D1 dopamine receptors in the striatum exerts
      a widespread facilitatory effect on cortical function.

PMID- 10884329
TI  - Synaptic interactions between thalamic inputs to simple cells in cat visual
      cortex.
AB  - We performed experiments in the cat geniculocortical pathway, in vivo, to examine
      how presynaptic spikes interact to influence the firing of postsynaptic targets.
      In particular, we asked (1) how do multiple spikes from a single presynaptic
      neuron interact to influence the firing of a postsynaptic target (homosynaptic
      interactions), (2) how do spikes from two different presynaptic neurons interact
      (heterosynaptic interactions), and (3) what is the time course of homosynaptic
      and heterosynaptic interactions? We found that both homosynaptic and
      heterosynaptic interactions increase the likelihood of driving a postsynaptic
      spike, although with different time courses. For two spikes traveling down a
      single geniculate axon, the second spike is more effective than the first for
      approximately 15 msec. For two spikes on separate axons, the interaction is
      faster ( approximately 7 msec duration, approximately 2.5 msec time constant).
      Thus changes in firing rate are perhaps best relayed by homosynaptic
      interactions, whereas heterosynaptic interactions may help detect coincident
      spikes from different thalamic inputs.

PMID- 10884330
TI  - Combined lesions of hippocampus and subiculum Do not produce deficits in a
      nonspatial social olfactory memory task.
AB  - Rats transmit information to each other about which foods are safe to eat. If a
      rat smells a food odor on the breath of another rat, it is subsequently more
      likely to eat that food than an alternative. Work by Galef et al. (1988) has
      shown that the observer rat forms an association between two olfactory stimuli on
      the breath of the demonstrator rat that has eaten the food, the food odor and
      carbon disulphide, which is normally present in the rat breath. Bunsey and
      Eichenbaum (1995) claimed that the hippocampus/subicular region is required for
      the long-term retention of this nonspatial form of associative memory on the
      basis that combined lesions of the hippocampus and subiculum produced a deficit,
      but lesions of either structure alone did not. We report here a failure to repeat
      this finding. Rats with either combined lesions of the hippocampus and subiculum
      or with amygdala lesions were tested on their ability to remember this
      association either immediately (testing short-term memory) or after a 24 hr delay
      (testing long-term memory). Neither lesion group exhibited significant memory
      deficits on this nonspatial associative task at either test interval. In
      contrast, a deficit was observed on a spatial memory task (forced-choice
      alternation t-maze) for animals with combined lesions of the hippocampus and
      subiculum. These results contradict the findings of Bunsey and Eichenbaum (1995)
      and support the idea that the hippocampus/subicular region is not required for
      this nonspatial associative memory.

PMID- 10884331
TI  - Increased excitability of aged rabbit CA1 neurons after trace eyeblink
      conditioning.
AB  - Cellular properties of CA1 neurons were studied in hippocampal slices 24 hr after
      acquisition of trace eyeblink conditioning in young adult and aging rabbits.
      Aging rabbits required significantly more trials than young rabbits to reach a
      behavioral criterion of 60% conditioned responses in an 80 trial session.
      Intracellular recordings revealed that CA1 neurons from aging control rabbits had
      significantly larger, longer lasting postburst afterhyperpolarizations (AHPs) and
      greater spike frequency adaptation (accommodation) relative to those from young
      adult control rabbits. After learning, both young and aging CA1 neurons exhibited
      increased postsynaptic excitability compared with their respective age-matched
      control rabbits (naive and rabbits that failed to learn). Thus, after learning,
      CA1 neurons from both age groups had reduced postburst AHPs and reduced
      accommodation. No learning-related differences were seen in resting membrane
      potential, membrane time constant, neuron input resistance, or action potential
      characteristics. Furthermore, comparisons between CA1 neurons from trace
      conditioned aging and trace-conditioned young adult rabbits revealed no
      statistically significant differences in postburst AHPs or accommodation,
      indicating that similar levels of postsynaptic excitability were attained during
      successful acquisition of trace eyeblink conditioning, regardless of rabbit age.
      These data represent the first in vitro demonstration of learning-related
      excitability changes in aging rabbit CA1 neurons and provide additional evidence
      for involvement of changes in postsynaptic excitability of CA1 neurons in both
      aging and learning.

PMID- 10884332
TI  - The midbrain precommand nucleus of the mormyrid electromotor network.
AB  - The functional role of the midbrain precommand nucleus (PCN) of the electromotor
      system was explored in the weakly electric mormyrid fish Gnathonemus petersii,
      using extracellular recording of field potentials, single unit activity, and
      microstimulation in vivo. Electromotor-related field potentials in PCN are linked
      in a one-to-one manner and with a fixed time relationship to the electric organ
      discharge (EOD) command cycle, but occur later than EOD command activity in the
      medulla. It is suggested that PCN electromotor-related field potentials arise
      from two sources: (1) antidromically, by backpropagation across electrotonic
      synapses between PCN axons and command nucleus neurons, and (2) as corollary
      discharge-driven feedback arriving from the command nucleus indirectly, via
      multisynaptic pathways. PCN neurons can be activated by electrosensory input, but
      this does not necessarily activate the whole motor command chain.
      Microstimulation of PCN modulates the endogenous pattern of electromotor command
      in a way that can mimic the structure of certain stereotyped behavioral patterns.
      PCN activity is regulated, and to a certain extent synchronized, by corollary
      discharge feedback inhibition. However, PCN does not generally function as a
      synchronized pacemaker driving the electromotor command chain. We propose that
      PCN neurons integrate information of various origins and individually relay this
      to the command nucleus in the medulla. Some may also have intrinsic, although
      normally nonsynchronized, pacemaker properties. This descending activity,
      integrated in the electromotor command nucleus, will play an important modulatory
      role in the central pattern generator decision process.

PMID- 10884333
TI  - Gastrin-releasing peptide phase-shifts suprachiasmatic nuclei neuronal rhythms in
      vitro.
AB  - The main mammalian circadian pacemaker is located in the suprachiasmatic nuclei
      (SCN) of the hypothalamus. Gastrin-releasing peptide (GRP) and its receptor
      (BB(2)) are synthesized by rodent SCN neurons, but the role of GRP in circadian
      rhythm processes is unknown. In this study, we examined the phase-resetting
      actions of GRP on the electrical activity rhythms of hamster and rat SCN neurons
      in vitro. In both rat and hamster SCN slices, GRP treatment during the day did
      not alter the time of peak SCN firing. In contrast, GRP application early in the
      subjective night phase-delayed, whereas similar treatment later in the subjective
      night phase-advanced the firing rate rhythm in rat and hamster SCN slices. These
      phase shifts were completely blocked by the selective BB(2) receptor antagonist,
      [d-Phe(6), Des-Met(14)]-bombesin 6-14 ethylamide. We also investigated the
      temporal changes in the expression of genes for the BB(1) and BB(2) receptors in
      the rat SCN using a quantitative competitive RT-PCR protocol. The expression of
      the genes for both receptors was easily detected, but their expression did not
      vary over the diurnal cycle. These data show that GRP phase-dependently phase
      resets the rodent SCN circadian pacemaker in vitro apparently via the BB(2)
      receptor. Because this pattern of phase shifting resembles that of light on
      rodent behavioral rhythms, these results support the contention that GRP
      participates in the photic entrainment of the rodent SCN circadian pacemaker.

PMID- 10884334
TI  - Periodicity and firing rate as candidate neural codes for the frequency of
      vibrotactile stimuli.
AB  - The flutter sensation is felt when mechanical vibrations between 5 and 50 Hz are
      applied to the skin. Neurons with rapidly adapting properties in the
      somatosensory system of primates are driven very effectively by periodic flutter
      stimuli; their evoked spike trains typically have a periodic structure with
      highly regular time differences between spikes. A long-standing conjecture is
      that, such periodic structure may underlie a subject's capacity to discriminate
      the frequencies of periodic vibrotactile stimuli and that, in primary
      somatosensory areas, stimulus frequency is encoded by the regular time intervals
      between evoked spikes, not by the mean rate at which these are fired. We examined
      this hypothesis by analyzing extracellular recordings from primary (S1) and
      secondary (S2) somatosensory cortices of awake monkeys performing a frequency
      discrimination task. We quantified stimulus-driven modulations in firing rate and
      in spike train periodicity, seeking to determine their relevance for frequency
      discrimination. We found that periodicity was extremely high in S1 but almost
      absent in S2. We also found that periodicity was enhanced when the stimuli were
      relevant for behavior. However, periodicity did not covary with psychophysical
      performance in single trials. On the other hand, rate modulations were similar in
      both areas, and with periodic and aperiodic stimuli, they were enhanced when
      stimuli were important for behavior, and were significantly correlated with
      psychophysical performance in single trials. Thus, the exquisitely timed,
      stimulus-driven spikes of primary somatosensory neurons may or may not contribute
      to the neural code for flutter frequency, but firing rate seems to be an
      important component of it.

PMID- 10884335
TI  - Timing mechanisms in the cerebellum: testing predictions of a large-scale
      computer simulation.
AB  - We used large-scale computer simulations of eyelid conditioning to investigate
      how the cerebellum generates and makes use of temporal information. In the
      simulations the adaptive timing displayed by conditioned responses is mediated by
      two factors: (1) different sets of granule cells are active at different times
      during the conditioned stimulus (CS), and (2) responding is not only amplified at
      reinforced times but also suppressed at unreinforced times during the CS. These
      factors predict an unusual pattern of responding after partial removal of the
      cerebellar cortex that was confirmed using small, electrolytic lesions of
      cerebellar cortex. These results are consistent with timing mechanisms in the
      cerebellum that are similar to Pavlov's "inhibition of delay" hypothesis.

PMID- 10884336
TI  - Firing rate of nucleus accumbens neurons is dopamine-dependent and reflects the
      timing of cocaine-seeking behavior in rats on a progressive ratio schedule of
      reinforcement.
AB  - The progressive ratio (PR) schedule of reinforcement is used to determine the
      reinforcing properties of rewards such as drugs of abuse. In this schedule, the
      animal is required to press a lever a progressively increasing number of times to
      receive a reward; the highest ratio obtained before the animal ceases responding
      is termed "breakpoint." We recorded neuronal spike activity from cells in the
      nucleus accumbens (NAc) of rats responding on a PR schedule for cocaine
      reinforcement. A common subtype of NAc cells demonstrated firing rates that
      varied according to the time between cocaine deliveries. The firing rate was
      inversely related to the NAc cocaine level predicted by a pharmacokinetic model.
      At higher response-to-reward ratios, inter-reward intervals were increased,
      resulting in a decrease in modeled cocaine level and a concomitant increase in
      firing rate over the session. The final increase in firing rate above a threshold
      value suggests a neural correlate of breakpoint. The effects of preadministration
      of dopamine D1 or D2 antagonists on the animals' behavior were similar in that
      both reduced breakpoint; however, each antagonist had markedly different effects
      on NAc cell firing. The D1 antagonist SCH23390 reduced firing rates, even at low
      cocaine levels, whereas the D2 antagonist eticlopride induced a rightward shift
      in the dose dependence of NAc cell firing relative to modeled cocaine level. Our
      results suggest that the firing of NAc cells reflects changes in cocaine levels
      and thereby contributes to the temporal spacing of self-administration and to the
      cessation of responding at breakpoint.

PMID- 10884337
TI  - Perinatal distress leads to lateralized medial prefrontal cortical dopamine
      hypofunction in adult rats.
AB  - Obstetric complications involving anoxia or prolonged hypoxia are suspected to
      increase the risk for such mental disorders as schizophrenia and attention
      deficit-hyperactivity disorder. In previous studies, we reported evidence of
      enhanced nucleus accumbens (NAcc) dopamine (DA) function in adult rats subjected
      to intrauterine anoxia during cesarean (C) section birth. In the present study,
      we used voltammetry and monoamine-sensitive electrodes to investigate the
      possibility that this functional hyperactivity of the meso-NAcc system is
      attributable to a loss of inhibitory control from the medial prefrontal cortex
      (PFC). We monitored the DA responses to repeated once-daily stress in the right
      or left PFC of adult male rats born vaginally (VAG) or by C-section, either with
      (C + 15) or without (C + 0) an additional 15 min of intrauterine anoxia. In C +
      15 animals, we observed a pronounced and persistent blunting of stress-induced DA
      release in the right PFC but not in the left; with repeated testing, a similar
      pattern of dampened right PFC DA stress responses emerged in C + 0 animals. In
      addition, C + 15 animals were spontaneously more active than VAG and C + 0
      animals and displayed an increase in PFC DA transporter density that was also
      lateralized to the right hemisphere. There was no evidence, however, that PFC
      D(1) and D(2) receptor levels differed between birth groups or hemisphere. These
      findings suggest a mechanism by which perinatal complications involving anoxia
      might contribute to the etiology of mental disorders that have been linked to
      disturbances in central DA transmission and lateralized PFC dysfunction.

PMID- 10884338
TI  - Granulocyte-macrophage colony-stimulating factor modulates rapid eye movement
      (REM) sleep and non-REM sleep in rats.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic
      cytokine that may affect various functions of the CNS because the molecule and
      its receptors are expressed in the brain. The present study examines the effects
      of GM-CSF on sleep using rats and the secretion of three
      neurotransmitters/hormones that are involved in sleep regulation. When infused
      intracerebroventricularly at doses as low as 10 pmol for 10 hr during the dark
      period, GM-CSF promoted predominantly rapid eye movement (REM) sleep and moderate
      amounts of non-REM sleep without eliciting fever. An injection of GM-CSF (3.0
      pmol) into the arcuate nucleus increased the release of nitric oxide (NO) from
      the hypothalamus but did not alter plasma levels of growth hormone. The release
      of somatostatin (SRIF) from the medial basal hypothalamus was stimulated by 1 x
      10(-)(11) M GM-CSF. These findings indicated that centrally administered GM-CSF
      stimulates SRIF release through activation of the NO system in the hypothalamus.
      Because SRIF promotes REM sleep, it may also mediate the effects of GM-CSF on REM
      sleep. The present study indicates a novel central effect of GM-CSF that
      modulates sleep, supporting the notion that hematopoietic cytokines also play
      roles in the CNS.

PMID- 10884339
TI  - Visual responses of neurons in the middle temporal area of new world monkeys
      after lesions of striate cortex.
AB  - In primates, lesions of striate cortex (V1) result in scotomas in which only
      rudimentary visual abilities remain. These aspects of vision that survive V1
      lesions have been attributed to direct thalamic pathways to extrastriate areas,
      including the middle temporal area (MT). However, studies in New World monkeys
      and humans have questioned this interpretation, suggesting that remnants of V1
      are responsible for both the activation of MT and residual vision. We studied the
      visual responses of neurons in area MT in New World marmoset monkeys in the weeks
      after lesions of V1. The extent of the scotoma in each case was estimated by
      mapping the receptive fields of cells located near the lesion border and by
      histological reconstruction. Two response types were observed among the cells
      located in the part of MT that corresponds, in visuotopic coordinates, to the
      lesioned part of V1. Many neurons (62%) had receptive fields that were displaced
      relative to their expected location, so that they represented the visual field
      immediately surrounding the scotoma. This may be a consequence of a process
      analogous to the reorganization of the V1 map after retinal lesions. However,
      another 20% of the cells had receptive fields centered inside the scotoma. Most
      of these neurons were strongly direction-selective, similar to normal MT cells.
      These results show that MT cells differ in their responses to lesioning of V1 and
      that only a subpopulation of MT neurons can be reasonably linked to residual
      vision and blindsight.

PMID- 10884340
TI  - A cholecystokinin-mediated pathway to the paraventricular thalamus is recruited
      in chronically stressed rats and regulates hypothalamic-pituitary-adrenal
      function.
AB  - Chronic stress alters hypothalamic-pituitary-adrenal (HPA) responses to acute,
      novel stress. After acute restraint, the posterior division of the
      paraventricular thalamic nucleus (pPVTh) exhibits increased numbers of Fos
      expressing neurons in chronically cold-stressed rats compared with stress-naive
      controls. Furthermore, lesions of the PVTh augment HPA activity in response to
      novel restraint only in previously stressed rats, suggesting that the PVTh is
      inhibitory to HPA activity but that inhibition occurs only in chronically
      stressed rats. In this study, we further examined pPVTh functions in chronically
      stressed rats. We identified afferent projections to the pPVTh using injection of
      the retrograde tracer fluorogold. Of the sites containing fluorogold-labeled
      cells, neurons in the lateral parabrachial, periaqueductal gray, and dorsal raphe
      containing fluorogold also expressed cholecystokinin (CCK) mRNA. We then examined
      whether these CCKergic inputs to the pPVTh were involved in HPA responses to
      acute, novel restraint after chronic stress. We injected the CCK-B receptor
      antagonist PD 135,158 into the PVTh before restraint in control and chronically
      cold-stressed rats. ACTH responses to restraint stress were augmented by PD
      135,158 only in chronically stressed rats but not in controls. In addition, CCK-B
      receptor mRNA expression in the pPVTh was not altered by chronic cold stress. We
      conclude that previous chronic stress specifically facilitates the release of CCK
      into the pPVTh in response to acute, novel stress. The CCK is probably secreted
      from neurons in the lateral parabrachial, the periaqueductal gray, and/or the
      dorsal raphe nuclei. Acting via CCK-B receptors in pPVTh, CCK then constrains
      facilitated ACTH responses to novel stress in chronically stressed but not naive
      rats. These results demonstrate clearly that chronic stress recruits a new set of
      pathways that modulate HPA responsiveness to a novel stress.

PMID- 10884341
TI  - Electron microscopic observation and single-stranded DNA binding activity of the
      Mcm4,6,7 complex.
AB  - Mcm2-7 proteins that play an essential role in eukaryotic DNA replication contain
      DNA-dependent ATPase motifs in a central domain that, from yeast to mammals, is
      highly conserved. Our group has reported that a DNA helicase activity is
      associated with a 600 kDa human Mcm4, 6 and 7 complex. The structure of the
      Mcm4,6,7 complex was visualized by electron microscopy after negative staining
      with uranyl acetate. The complex contained toroidal forms with a central channel
      and also contained structures with a slit. Gel-shift analysis indicated that the
      level of affinity of the Mcm4,6,7 complex for single-stranded DNA was comparable
      to that of SV40 T antigen, although the Mcm4,6,7 complex required longer single
      stranded DNA for the binding than did SV40 T antigen. The nucleoprotein complexes
      of Mcm4,6,7 and single-stranded DNA were visualized as beads in a queue or beads
      on string-like structures. The formation of these nucleoprotein complexes was
      erased by Mcm2 that is a potential inhibitor of the Mcm4,6,7 helicase. We also
      found that the DNA helicase activity of Mcm4,6,7 complex was inhibited by the
      binding of Mcm3,5 complex. These results support the notion that the Mcm4,6,7
      complex functions as a DNA helicase and the formation of 600 kDa complex is
      essential for the activity.

PMID- 10884342
TI  - Diverse Caenorhabditis elegans genes that are upregulated in dauer larvae also
      show elevated transcript levels in long-lived, aged, or starved adults.
AB  - Under adverse conditions, the nematode Caenorhabditis elegans undergoes
      reversible developmental arrest as dauer larvae, an alternative third larval
      stage adapted for dispersal and long-term survival. Following such arrest, which
      may exceed three times their usual life-span, worms resume development to form
      reproductive adults of normal subsequent longevity. Mutations of genes in the
      dauer-formation (daf) pathway can extend life-span two- to fourfold, even in
      adults that mature without diapause. To identify transcript-level changes that
      might contribute to extended survival, we prepared a subtractive cDNA library of
      messages more abundant in dauer than in non-dauer (L3) larvae. Six genes were
      confirmed as three- to ninefold upregulated in dauer larvae, after correction for
      mRNA load: genes encoding poly(A)-binding protein (PABP), heat-shock proteins
      hsp70 and hsp90, and three novel genes of uncertain function. The novel genes
      encode a partial homologue of human activating signal cointegrator 1 (ASC-1), a
      GTP-binding homologue of a ribosomal protein, and an SH3-domain protein.
      Transcript levels for all except hsp70 increased during aging in two C. elegans
      strains, whereas the three novel genes (and possibly PABP) were also induced to
      varying degrees by starvation of adults. All six genes are expressed at higher
      levels in young adults of long-lived daf mutant strains than in normal-longevity
      controls, suggesting that increased expression of these genes may play a
      protective function, thus favoring survival in diverse contexts.

PMID- 10884343
TI  - Distinct RNA structural domains cooperate to maintain a specific cleavage site in
      the 3'-UTR of IGF-II mRNAs.
AB  - The insulin-like growth factor II mRNAs are targets for site-specific
      endonucleolytic cleavage in the 3'-UTR, which results in a very stable 3'
      cleavage product of 1.8 kb, consisting of 3'-UTR sequences and a poly(A) tail.
      The 5' cleavage product contains the coding region and is rapidly degraded. Thus,
      cleavage is thought to provide an additional way to control IGF-II protein
      synthesis. We had established that cleavage requires two widely separated
      sequence elements (I and II) in the 3'-UTR that form a stable duplex of 83
      nucleotides. The cleavage-site itself is located in an internal loop preceded by
      two stable stem-loop structures. Furthermore, in a study which was based on RNA
      folding algorithms, we have shown that there are specific sequence and structural
      requirements for the cleavage reaction. Here, the functions of the different
      structural domains in cleavage were assessed by deletion/mutational analyses, and
      biochemical structure probing assays were performed to characterize better the
      RNA structures formed and to verify the computer folding predictions. The data
      suggest that the stem-loop domain contributes to maintain a highly specific c
      leavage-site by preventing the formation of alternative structures in the
      cleavage-site domain. Involvement of the nucleotides in the cleavage-site loop
      itself in non-Watson-Crick interactions may be important for providing a specific
      recognition surface for an endoribonuclease activity.

PMID- 10884344
TI  - A novel, 11 nucleotide variant of chi, chi*: one of a class of sequences defining
      the Escherichia coli recombination hotspot chi.
AB  - In wild-type Escherichia coli, recognition of the recombination hotspot, chi (5'
      GCTGGTGG-3'), by the RecBCD enzyme is central to homologous recombination.
      However, in the recC* class of RecBCD mutants, stimulation of recombination by
      the canonical chi sequence is not detectable, but the levels of homologous
      recombination are nearly wild-type. In vivo studies demonstrate that a member of
      this class of mutants, the recC1004 allele, encodes an enzyme that responds to a
      novel variant of chi, termed chi* (5'-GCTGGTGCTCG-3'). Here, we establish that,
      in vitro, the chi* sequence is recognized more efficiently by the RecBC(1004)D
      enzyme than is the wild-type chi. This is manifest by both a greater modification
      of nuclease activity and a higher stimulation of RecA protein-mediated joint
      molecule formation at chi* than at chi. Sequencing of the recC1004 gene revealed
      that it contains a frameshift mutation, which results in a replacement of nine of
      the wild-type amino acid residues by eight in the mutant protein, and defines a
      locus that is important for the specificity of chi-recognition. In addition, we
      show that this novel, 11 nucleotide chi* sequence also regulates the wild-type
      RecBCD enzyme, supporting the notion that variants of the canonical chi
      constitute a class of sequences that regulate the recombination function of
      RecBCD enzyme.

PMID- 10884345
TI  - Increased sensitivity to quinolone antibacterials can be engineered in human
      topoisomerase IIalpha by selective mutagenesis.
AB  - A potential region of drug-DNA interaction in the A subunit of DNA gyrase has
      previously been identified from crystallographic studies. The local amino acid
      sequence has been compared with similar regions in yeast topoisomerase II and
      human topoisomerase IIalpha. Three non- conserved, potentially solvent-accessible
      residues at positions 762, 763 and 766 in human topoisomerase IIalpha lie between
      well-conserved regions. The corresponding residues in GyrA (83, 84 and 87) have a
      high frequency of mutation in quinolone-resistant bacteria. Mutations in human
      topoisomerase IIalpha have been generated in an attempt to engineer ciprofloxacin
      sensitivity into this enzyme: M762S, S763A and M766D (each mutated to the
      identical amino acid present in gyrase), along with an M762S/S763A double mutant
      and a triple mutant. These enzymes were introduced into a temperature-sensitive
      yeast strain, deficient in topoisomerase II, for in vivo studies, and were
      overproduced for in vitro studies. The M766D mutation renders the enzyme
      incapable of supporting the temperature-sensitive strain at a non-permissive
      temperature. However, both M766D and the triple mutant enzymes can be
      overproduced and are fully active in vitro. The double mutant was impaired in its
      ability to cleave DNA and had reduced catalytic activity. The triple mutation
      confers a three-fold increase in sensitivity to ciprofloxacin in vitro and
      similar sensitivities to a range of other quinolones. The activity of the
      quinolone CP-115,953, a bacterial and eukaryotic topoisomerase II poison, was
      unaffected by any of these mutations. Mutations in this region were found to
      increase the sensitivity of the enzyme to the DNA intercalating anti-tumour
      agents m-AMSA and ellipticine, but confer resistance to the non-intercalating
      agents etoposide, teniposide and merbarone, an effect that was maximal in the
      triple mutant. We have therefore shown the importance of this region in
      determining the sensitivity of topoisomerase II to drugs and have engineered
      increased sensitivity to quinolones.

PMID- 10884346
TI  - Substrate binding is a prerequisite for stabilisation of mouse thymidine kinase
      in proliferating fibroblasts.
AB  - Thymidine kinase (TK) expression in mammalian cells is strictly growth regulated,
      with high levels of the enzyme present in proliferating cells and low levels in
      resting cells. We have shown that mouse TK expressed from a constitutive promoter
      is still subject to this regulation. The drastic decline in TK enzyme levels in
      resting cells is largely due to a pronounced reduction in the half-life of the
      protein. Deletion of the 30 C-terminal amino acid residues from TK abrogates
      growth regulation, rendering the enzyme very stable. Moreover, the substrate
      thymidine was sufficient to stabilise the labile TK protein in quiescent cells.
      Here, we report that the ability of TK to bind substrates is essential for both
      growth-dependent regulation and stabilisation by the substrate. By mutation or
      elimination of the binding sites for either of the two substrates, ATP and
      thymidine, we expressed TK proteins lacking enzymatic activity which abolished
      growth-regulated expression in both cases. Mutant TK proteins impaired in
      substrate binding were subject to rapid degradation in exponentially growing
      cells and thymidine was no longer sufficient to inhibit this rapid decay. A C
      terminal truncation known to stabilise the TK wild-type protein in resting cells
      did not affect the rapid turnover of enzymatically inactive TK proteins.
      Proteasome inhibitors also failed to stabilise these substrate-binding mutants.
      By cross-linking experiments, we show that TK proteins with mutated substrate
      binding sites exist only as monomers, whereas active TK enzyme forms dimers and
      tetramers. Our data indicate that, In addition to the C terminus intact substrate
      binding sites are required for growth-dependent regulation of TK protein
      stability.

PMID- 10884347
TI  - The C-terminal regulatory domain of p53 contains a functional docking site for
      cyclin A.
AB  - Radiation injury to cells enhances C-terminal phosphorylation of p53 at both
      Ser315 and Ser392 in vivo, suggesting the existence of two cooperating DNA damage
      responsive pathways that play a role in stimulating p53-dependent gene
      expression. Our previous data has shown that cyclin A-cdk2 is the major enzyme
      responsible for modifying p53 at Ser315 in vivo after irradiation damage and in
      this report we dissect the mechanism of cyclinA-cdk2 binding to and
      phosphorylation of p53. Although cyclin B(1)-dependent protein kinases can
      phosphorylate small peptides containing the Ser315 site, cyclin A-cdk2 does not
      phosphorylate such small peptides suggesting that additional determinants are
      required for cyclin A-cdk2 interaction with p53. Peptide competition studies have
      localized a cyclin A interaction site to a Lys381Lys382Leu383Met384Phe385
      sequence within C-terminal negative regulatory domain of human p53. An alanine
      mutation at any one of four key positions abrogates the efficacy of a synthetic
      peptide containing this motif as an inhibitor of cyclin A-cdk2 phosphorylation of
      p53 protein. Single amino acid mutations of full-length p53 protein at Lys382,
      Leu383, or Phe385 decreases cyclin A-cdk2 dependent phosphorylation at Ser315.
      Cyclin B(1)-cdk2 complexes are not inhibited by KKLMF motif-containing peptides
      nor is p53 phosphorylation by cyclin B-cdk2 reduced by mutation of the cyclin A
      interaction site. These data identifying a KKLMF cyclin A docking site on p53
      protein highlight a common cyclin A interaction motif that is shared between the
      tumour suppressor proteins pRb and p53.

PMID- 10884348
TI  - Ran alters nuclear pore complex conformation.
AB  - Transport across the nuclear membranes occurs through the nuclear pore complex
      (NPC), and is mediated by soluble transport factors including Ran, a small GTPase
      that is generally GDP-bound during import and GTP-bound for export. The dynamic
      nature of the NPC structure suggests a possible active role for it in driving
      translocation. Here we show that RanGTP but not RanGDP causes alterations of NPC
      structure when injected into the cytoplasm of Xenopus oocytes, including
      compaction of the NPC and extension of the cytoplasmic filaments. RanGTP caused
      accumulation of nucleoplasmin-gold along the length of extended cytoplasmic
      filaments, whereas RanGDP caused accumulation around the cytoplasmic rim of the
      NPC. This suggests a possible role for Ran in altering the conformation of the
      cytoplasmic filaments during transport.

PMID- 10884349
TI  - Echinoderm collagen fibrils grow by surface-nucleation-and-propagation from both
      centers and ends.
AB  - Collagen fibrils from sea cucumber (class Holothuroidea) dermis were previously
      found to grow by coordinated monomer addition at both centers and ends. This
      analysis of sea urchin (class Echinoidea) collagen fibrils was undertaken to
      compare the growth characteristics of fibrils from two classes of echinoderms,
      and to determine whether a single growth model could account for the main
      features of fibrils from these two taxa. Native collagen fibrils (37-431
      micrometer long) from the spine ligaments of the sea urchin Eucidaris tribuloides
      were studied by scanning transmission electron microscopy and image analysis. The
      analyses revealed the mass per unit length, and hence the number of molecules in
      cross-section, along the entire length of each fibril. The fibrils were
      symmetrically spindle shaped. The maximum mass per unit length occurred in the
      center of each fibril, where the fibril contains anti-parallel molecules in equal
      numbers. The two pointed tips of each fibril showed similar linear axial mass
      distributions, indicating that the two tips retain shape and size similarity
      throughout growth. The linear axial mass distributions showed that the tips were
      paraboloidal, similar to those of vertebrate and sea cucumber fibrils. The
      computed maximum diameters of the fibrils increased linearly with fibril length.
      The overall shapes of the fibrils showed that they retain geometric similarity
      throughout growth. Computer modeling showed that the simplest self-assembly
      mechanism that can account for the features of these fibrils, and of the sea
      cucumber fibrils that have been described, is one in which the fibril tips
      produce independent axial growth, while lateral growth takes place through a
      surface nucleation and propagation mechanism. This mechanism produces coordinated
      growth in length and diameter as well as geometric similarity, characteristic
      features of echinoderm collagen fibrils.

PMID- 10884351
TI  - A new crystal form for the dodecamer C-G-C-G-A-A-T-T-C-G-C-G: symmetry effects on
      sequence-dependent DNA structure.
AB  - The dodecanucleotide d(CGCGAATTCGCG) has been crystallised in the space group
      P3(2)12, representing a new crystal form for this sequence. The structure has
      been solved by molecular replacement and refined at 1.8 A resolution. The present
      structure contrasts with previous ones for this sequence since it is situated on
      a crystallographic 2-fold axis, and the crystal symmetry reflects the palindromic
      nature of this sequence. Some features accord with previous observations, notably
      that the minor groove is hydrated with a continuous spine of solvent. There is no
      evidence of alkali metal ions within this spine. The minor groove retains its
      narrow width, although it is now symmetric and extends over the A/T tract.
      Various base and base-pair morphological parameters have been examined. Their
      values do not show significant correlations with earlier reports, suggesting that
      crystal packing effects on them are more dominant than has been hitherto
      realised.

PMID- 10884350
TI  - Formation and seeding of amyloid fibrils from wild-type hen lysozyme and a
      peptide fragment from the beta-domain.
AB  - Wild-type hen lysozyme has been converted from its soluble native state into
      highly organized amyloid fibrils. In order to achieve this conversion, conditions
      were chosen to promote partial unfolding of the native globular fold and included
      heating of low-pH solutions and addition of organic solvents. Two peptides
      derived from the beta-sheet region of hen lysozyme were also found to form
      fibrils very readily. The properties and morphologies of the amyloid fibrils
      formed by incubation either of the protein or the peptides are similar to those
      produced from the group of proteins associated with clinical amyloidoses. Fibril
      formation by hen lysozyme was substantially accelerated when aliquots of
      solutions in which fibrils of either one of the peptides or the full-length
      protein had previously formed were added to fresh solutions of the protein,
      revealing the importance of seeding in the kinetics of fibril formation. These
      findings support the proposition that the beta-domain is of particular
      significance in the formation of fibrils from the full-length protein and suggest
      similarities between the species giving rise to fibril formation and the
      intermediates formed during protein folding.

PMID- 10884352
TI  - Solution structural studies and low-resolution model of the Schizosaccharomyces
      pombe sap1 protein.
AB  - Sap1 is a DNA-binding protein involved in controlling the mating type switch in
      fission yeast Schizosaccharomyces pombe. In the absence of any significant
      sequence similarity with any structurally known protein, a variety of biophysical
      techniques has been used to probe the solution low-resolution structure of the
      sap1 protein. First, sap1 is demonstrated to be an unusually elongated dimer in
      solution by measuring the translational diffusion coefficient with two
      independent techniques: dynamic light-scattering and ultracentrifugation. Second,
      sequence analysis revealed the existence of a long coiled-coil region, which is
      responsible for dimerization. The length of the predicted coiled-coil matches
      estimates drawn from the hydrodynamic experimental behaviour of the molecule. In
      addition, the same measurements done on a shorter construct with a coiled-coil
      region shortened by roughly one-half confirmed the localization of the long
      coiled-coil region. A crude T-shape model incorporating all these information was
      built. Third, small-angle X-ray scattering (SAXS) of the free molecule provided
      additional evidence for the model. In particular, the P(r) curve strikingly
      demonstrates the existence of long intramolecular distances. Using a novel 3D
      reconstruction algorithm, a low resolution 3D model of the protein has been
      independently constructed that matches the SAXS experimental data. It also fits
      the translation diffusion coefficients measurements and agrees with the first T
      shaped model. This low-resolution model has clearly biologically relevant new
      functional implications, suggesting that sap1 is a bifunctional protein, with the
      two active sites being separated by as much as 120 A; a tetrapeptide repeated
      four times at the C terminus of the molecule is postulated to be of utmost
      functional importance.

PMID- 10884353
TI  - Crystal structure of Streptomyces olivaceoviridis E-86 beta-xylanase containing
      xylan-binding domain.
AB  - Xylanases hydrolyse the beta-1,4-glycosidic bonds within the xylan backbone and
      belong to either family 10 or 11 of the glycoside hydrolases, on the basis of the
      amino acid sequence similarities of their catalytic domains. Generally, xylanases
      have a core catalytic domain, an N and/or C-terminal substrate-binding domain and
      a linker region. Until now, X-ray structural analyses of family 10 xylanases have
      been reported only for their catalytic domains and do not contain substrate
      binding domains. We have determined the crystal structure of a family 10 xylanase
      containing the xylan-binding domain (XBD) from Streptomyces olivaceoviridis E-86
      at 1.9 A resolution. The catalytic domain comprises a (beta/alpha)(8)-barrel
      topologically identical to other family 10 xylanases. XBD has three similar
      subdomains, as suggested from a triple-repeat sequence, which are assembled
      against one another around a pseudo-3-fold axis, forming a galactose-binding
      lectin fold similar to ricin B-chain. The Gly/Pro-rich linker region connecting
      the catalytic domain and XBD is not visible in the electron density map, probably
      because of its flexibility. The interface of the two domains in the crystal is
      hydrophilic, where five direct hydrogen bonds and water-mediated hydrogen bonds
      exist. The sugar-binding residues seen in ricin/lactose complex are spatially
      conserved among the three subdomains in XBD, suggesting that all of the
      subdomains in XBD have the capacity to bind sugars. The flexible linker region
      enables the two domains to move independently and may provide a triple chance of
      substrate capturing and catalysis. The structure reported here represents an
      example where the metabolic enzyme uses a ricin-type lectin motif for capturing
      the insoluble substrate and promoting catalysis.

PMID- 10884354
TI  - Structure of a thioredoxin-like [2Fe-2S] ferredoxin from Aquifex aeolicus.
AB  - The 2.3 A resolution crystal structure of a [2Fe-2S] cluster containing
      ferredoxin from Aquifex aeolicus reveals a thioredoxin-like fold that is novel
      among iron-sulfur proteins. The [2Fe-2S] cluster is located near the surface of
      the protein, at a site corresponding to that of the active-site disulfide bridge
      in thioredoxin. The four cysteine ligands are located near the ends of two
      surface loops. Two of these ligands can be substituted by non-native cysteine
      residues introduced throughout a stretch of the polypeptide chain that forms a
      protruding loop extending away from the cluster. The presence of homologs of this
      ferredoxin as components of more complex anaerobic and aerobic electron transfer
      systems indicates that this is a versatile fold for biological redox processes.

PMID- 10884355
TI  - Host range and variability of calcium binding by surface loops in the capsids of
      canine and feline parvoviruses.
AB  - Canine parvovirus (CPV) emerged in 1978 as a host range variant of feline
      panleukopenia virus (FPV). This change of host was mediated by the mutation of
      five residues on the surface of the capsid. CPV and FPV enter cells by
      endocytosis and can be taken up by many non-permissive cell lines, showing that
      their host range and tissue specificity are largely determined by events
      occurring after cell entry. We have determined the structures of a variety of
      strains of CPV and FPV at various pH values and in the presence or absence of
      Ca(2+). The largest structural difference was found to occur in a flexible
      surface loop, consisting of residues 359 to 375 of the capsid protein. This loop
      binds a divalent calcium ion in FPV and is adjacent to a double Ca(2+)-binding
      site, both in CPV and FPV. Residues within the loop and those associated with the
      double Ca(2+)-binding site were found to be essential for virus infectivity. The
      residues involved in the double Ca(2+)-binding site are conserved only in FPV and
      CPV. Our results show that the loop conformation and the associated Ca(2+)
      binding are influenced by the Ca(2+) concentration, as well as pH. These changes
      are correlated with the ability of the virus to hemagglutinate erythrocytes. The
      co-localization of hemagglutinating activity and host range determinants on the
      virus surface implies that these properties may be functionally linked. We
      speculate that the flexible loop and surrounding regions are involved in binding
      an as yet unidentified host molecule and that this interaction influences host
      range.

PMID- 10884356
TI  - Structures of chitobiase mutants complexed with the substrate Di-N-acetyl-d
      glucosamine: the catalytic role of the conserved acidic pair, aspartate 539 and
      glutamate 540.
AB  - The catalytic domain of chitobiase (beta-N-1-4 acetylhexosaminidase) from
      Serratia marcescens, is an alpha/beta TIM-barrel. This enzyme belongs to family
      20 of glycosyl hydrolases in which a conserved amino acid pair, aspartate
      glutamate, is present (Asp539-Glu540). It was proposed that catalysis by this
      enzyme family is carried out by glutamate 540 acting as a proton donor and by the
      acetamido group of the substrate as a nucleophile. We investigated the role of
      Asp539 and Glu540 by site-directed mutagenesis, biochemical characterization and
      by structural analyses of chitobiase -substrate co-crystals. We found that both
      residues are essential for chitobiase activity. The mutations, however, led to
      subtle changes in the catalytic site. Our results support the model that Glu540
      acts as the proton donor and that Asp539 acts in several different ways. Asp539
      restrains the acetamido group of the substrate in a specific orientation by
      forming a hydrogen bond with N2 of the non-reduced (-1) sugar. In addition, this
      residue participates in substrate binding. It is also required for the correct
      positioning of Glu540 and may provide additional negative charge at the active
      site. Thus, these biochemical and structural studies provide a molecular
      explanation for the functional importance and conservation of these residues.

PMID- 10884357
TI  - Binding of retinol induces changes in rat cellular retinol-binding protein II
      conformation and backbone dynamics.
AB  - The structure and backbone dynamics of rat holo cellular retinol-binding protein
      II (holo-CRBP II) in solution has been determined by multidimensional NMR. The
      final structure ensemble was based on 3980 distance and 30 dihedral angle
      restraints, and was calculated using metric matrix distance geometry with
      pairwise Gaussian metrization followed by simulated annealing. The average RMS
      deviation of the backbone atoms for the final 25 structures relative to their
      mean coordinates is 0.85(+/-0.09) A. Comparison of the solution structure of holo
      CRBP II with apo-CRBP II indicates that the protein undergoes conformational
      changes not previously observed in crystalline CRBP II, affecting residues 28-35
      of the helix-turn-helix, residues 37-38 of the subsequent linker, as well as the
      beta-hairpin C-D, E-F and G-H loops. The bound retinol is completely buried
      inside the binding cavity and oriented as in the crystal structure. The order
      parameters derived from the (15)N T(1), T(2) and steady-state NOE parameters show
      that the backbone dynamics of holo-CRBP II is restricted throughout the
      polypeptide. The T(2) derived apparent backbone exchange rate and amide (1)H
      exchange rate both indicate that the microsecond to second timescale
      conformational exchange occurring in the portal region of the apo form has been
      suppressed in the holo form.

PMID- 10884358
TI  - Stabilisation of alpha-helices by site-directed mutagenesis reveals the
      importance of secondary structure in the transition state for acylphosphatase
      folding.
AB  - The effects of stabilising mutations on the folding process of common-type
      acylphosphatase have been investigated. The mutations were designed to increase
      the helical propensity of the regions of the polypeptide chain corresponding to
      the two alpha-helices of the native protein. Various synthetic peptides
      incorporating the designed mutations were produced and their helical content
      estimated by circular dichroism. The most substantial increase in helical content
      is found for the peptide carrying five mutations in the second alpha-helix.
      Acylphosphatase variants containing the corresponding mutations display, to
      different extents, enhanced conformational stabilities as indicated by
      equilibrium urea denaturation experiments monitored by changes of intrinsic
      fluorescence. All the protein variants studied here refold with apparent two
      state kinetics. Mutations in the first alpha-helix are responsible for a small
      increase in the refolding rate, accompanied by a marked decrease in the unfolding
      rate. On the other hand, multiple mutations in the second helix result in a
      considerable increase in the refolding rate without any significant effect on the
      unfolding rate. Addition of trifluoroethanol was found to accelerate the folding
      of the acylphosphatase variants, the extent of the acceleration being inversely
      proportional to the intrinsic rate of folding of the corresponding mutant. The
      trifluoroethanol-induced acceleration is far less marked for those variants whose
      alpha-helical structure is efficiently stabilised by amino acid replacements.
      This observation suggests that trifluoroethanol acts in a similar manner to the
      stabilising mutations in promoting native-like secondary structure. Analysis of
      the kinetic data indicates that the second helix is fully consolidated in the
      transition state for folding of acylphosphatase, whereas the first helix is only
      partially formed. These data suggest that the second helix is an important
      element in the folding process of the protein.

PMID- 10884359
TI  - Accurate formula for P-values of gapped local sequence and profile alignments.
AB  - A simple general approximation for the distribution of gapped local alignment
      scores is presented, suitable for assessing significance of comparisons between
      two protein sequences or a sequence and a profile. The approximation takes
      account of the scoring scheme (i.e. gap penalty and substitution matrix or
      profile), sequence composition and length. Use of this formula means it is
      unnecessary to fit an extreme-value distribution to simulations or to the results
      of databank searches. The method is based on the theoretical ideas introduced by
      R. Mott and R. Tribe in 1999. Extensive simulation studies show that score
      thresholds produced by the method are accurate to within +/-5 % 95 % of the time.
      We also investigate factors which effect the accuracy of alignment statistics,
      and show that any method based on asymptotic theory is limited because asymptotic
      behaviour is not strictly achieved for many real protein sequences, due to
      extreme composition effects. Consequently, it may not be practicable to find a
      general formula that is significantly more accurate until the sub-asymptotic
      behaviour of alignments is better understood.

PMID- 10884360
TI  - All LODs are not created equal.

PMID- 10884361
TI  - Statistical approaches to gene mapping.

PMID- 10884362
TI  - Vascular gp91(phox): beyond the endothelium.

PMID- 10884363
TI  - Regulation of vascular tone: role of 20-HETE in the modulation of myogenic
      reactivity.

PMID- 10884364
TI  - The real thing.

PMID- 10884365
TI  - Cardiac intracellular calcium release channels: role in heart failure.

PMID- 10884366
TI  - Role of the JAK/STAT pathway in rat carotid artery remodeling after vascular
      injury.
AB  - In cultured vascular smooth muscle cells (VSMCs), Janus kinases (JAKs) and signal
      transducers and activators of transcription (STATs) are expressed constitutively
      and play a role in angiotensin II (Ang II)-induced intracellular signaling and
      proliferation. However, little is known regarding the relevance of these proteins
      to the process of vascular remodeling. The role of JAK and STAT proteins in
      vascular remodeling and their functional coupling with Ang II were examined in
      balloon-injured rat carotid artery. Immunoreactive Jak2, Tyk2, Stat1, and Stat3
      were not detected in the intact artery. Immunohistostaining showed transient
      expressions of these JAKs and STATs in medial and neointimal VSMCs at days 2 and
      5, respectively, with a peak at day 7 in both layers. The expressions declined to
      insignificant levels by day 14. Ang II type 1 receptors (AT(1)s) were coexpressed
      in the medial and neointimal VSMCs expressing Jak2 and Stat3. The Jak2 and Stat3
      inductions in the injured artery were accompanied by constitutive Jak2 and Stat3
      phosphorylations, which were enhanced by ex vivo Ang II stimulation via AT(1).
      Additionally, a Jak2 inhibitor, AG490, blocked the Ang II-induced Stat3
      phosphorylation. Furthermore, local treatment with AG490 inhibited constitutive
      Stat3 phosphorylation and neointimal VSMC replication and subsequently reduced
      neointima formation in the injured artery. In conclusion, JAK and STAT proteins
      were inducible in medial and neointimal VSMCs after vascular injury and were
      functionally coupled to AT(1). The inductions of JAKs and STATs would be involved
      in the mechanisms of neointima formation after vascular injury.

PMID- 10884367
TI  - Estrogens and glucocorticoids inhibit endothelial vascular cell adhesion molecule
      1 expression by different transcriptional mechanisms.
AB  - The antiatherogenic effect of estrogen is mediated, in part, by inhibitory
      effects on endothelial vascular cell adhesion molecule-1 (VCAM-1) expression. To
      determine the mechanism by which estrogen regulates VCAM-1 expression, we
      compared the effect of 17beta-estradiol (E(2)) and of the glucocorticoid
      dexamethasone (Dex) on lipopolysaccharide (LPS)-induced VCAM-1 expression in
      human endothelial cells. E(2) decreased LPS-induced VCAM-1 mRNA and protein
      expression to a greater extent than Dex. Dex, but not E(2), stabilized VCAM-1
      mRNA. This correlated with inhibition of monocytoid U937 cell adhesion to
      endothelial cells. Transfection of endothelial cells with a functional VCAM-1
      promoter construct showed that E(2) inhibited LPS-induced VCAM-1 gene
      transcription more potently than did Dex. However, using a truncated construct
      containing only the nuclear factor-kappaB (NF-kappaB)-responsive elements but
      lacking the consensus sequences for activator protein-1 (AP-1) and GATA, E(2) and
      Dex had similar inhibitory effects. Consistently, gel-shift assays showed that
      E(2) and Dex comparably inhibit LPS-induced activation of NF-kappaB, whereas E(2)
      inhibited LPS-induced activation of AP-1 and GATA to a greater extent than Dex.
      E(2) inhibition of NF-kappaB after LPS treatment was associated with decreased
      inhibitor kappaB (IkappaB) kinase activity and with a stabilization of the NF
      kappaB inhibitor IkappaBalpha. These results indicate that E(2) decreases VCAM-1
      gene expression through the inhibition of NF-kappaB, AP-1, and GATA and suggest
      novel mechanisms for the antiatherogenic effect of estrogen on the vascular wall.

PMID- 10884368
TI  - A gp91phox containing NADPH oxidase selectively expressed in endothelial cells is
      a major source of oxygen radical generation in the arterial wall.
AB  - Reactive oxygen species (ROS) play an important role in regulating vascular tone
      and intracellular signaling; the enzymes producing ROS in the vascular wall are,
      however, poorly characterized. We investigated whether a functionally active
      NADPH oxidase similar to the leukocyte enzyme, ie, containing the subunits
      p22phox and gp91phox, is expressed in endothelial cells (ECs) and smooth muscle
      cells (SMCs). Phorbol 12-myristate 13-acetate (PMA), a stimulus for leukocyte
      NADPH oxidase, increased ROS generation in cultured ECs and endothelium-intact
      rat aortic segments, but not in SMCs or endothelium-denuded arteries. NADPH
      enhanced chemiluminescence in all preparations. p22phox mRNA and protein was
      detected in ECs and SMCs, whereas the expression of gp91phox was confined to ECs.
      Endothelial gp91phox was identical to the leukocyte form as determined by
      sequence analysis. In contrast, mitogenic oxidase-1 (mox1) was expressed in SMCs,
      but not in ECs. To determine the functional relevance of gp91phox expression,
      experiments were performed in aortic segments from wild-type, gp91phox(-/-), and
      endothelial NO synthase (eNOS)(-/-) mice. PMA-induced ROS generation was
      comparable in aortae from wild-type and eNOS(-/-) mice, but was attenuated in
      segments from gp91phox(-/-) mice. Endothelium-dependent relaxation was greater in
      aortae from gp91phox(-/-) than from wild-type mice. The ROS scavenger tiron
      increased endothelium-dependent relaxation in segments from wild-type, but not
      from gp91phox(-/-) mice. These data demonstrate that ECs, in contrast to SMCs,
      express a gp91phox-containing leukocyte-type NADPH oxidase. This enzyme is a
      major source for arterial ROS generation and affects the bioavailability of
      endothelium-derived NO.

PMID- 10884369
TI  - Activation of protein kinase A modulates trafficking of the human cardiac sodium
      channel in Xenopus oocytes.
AB  - Voltage-gated Na(+) channels are critical determinants of electrophysiological
      properties in the heart. Stimulation of beta-adrenergic receptors, which activate
      cAMP-dependent protein kinase (protein kinase A [PKA]), can alter impulse
      conduction in normal tissue and promote development of cardiac arrhythmias in
      pathological states. Recent studies demonstrate that PKA activation increases
      cardiac Na(+) currents, although the mechanism of this effect is unknown. To
      explore the molecular basis of Na(+) channel modulation by beta-adrenergic
      receptors, we have examined the effects of PKA activation on the recombinant
      human cardiac Na(+) channel, hH1. Both in the absence and the presence of
      hbeta(1) subunit coexpression, activation of PKA caused a slow increase in Na(+)
      current that did not saturate despite kinase stimulation for 1 hour. In addition,
      there was a small shift in the voltage dependence of channel activation and
      inactivation to more negative voltages. Chloroquine and monensin, compounds that
      disrupt plasma membrane recycling, reduced hH1 current, suggesting rapid turnover
      of channels at the cell surface. Preincubation with these agents also prevented
      the PKA-mediated rise in Na(+) current, indicating that this effect likely
      resulted from an increased number of Na(+) channels in the plasma membrane.
      Experiments using chimeric constructs of hH1 and the skeletal muscle Na(+)
      channel, hSKM1, identified the I-II interdomain loop of hH1 as the region
      responsible for the PKA effect. These results demonstrate that activation of PKA
      modulates both trafficking and function of the hH1 channel, with changes in Na(+)
      current that could either speed or slow conduction, depending on the
      physiological circumstances.

PMID- 10884370
TI  - beta(2)-adrenoceptors activate nitric oxide synthase in human platelets.
AB  - Nitric oxide (NO), generated by platelets through stimulation of nitric oxide
      synthase (NOS), limits platelet adhesion and aggregation after a prothrombotic
      stimulus. Platelet beta-adrenoceptors (betaARs) mediate inhibition of
      aggregation, but no direct link has been shown between these receptors and
      platelet adhesion or NO production. We examined NOS activity in human platelets
      from the conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline, after betaAR
      stimulation or cAMP elevation. Basal NOS activity was 0.11+/-0.03 pmol L
      citrulline/10(8) platelets. The betaAR agonist isoproterenol 1 micromol/L and the
      adenylyl cyclase activator forskolin 1 micromol/L each increased NOS activity, to
      0.26+/-0.04 and 0.23+/-0.03 pmol L-citrulline/10(8) platelets, respectively
      (P<0.01 for each). Both responses were abolished by the adenylyl cyclase
      inhibitor SQ22536 50 micromol/L. NOS activation by isoproterenol or forskolin was
      not associated with a change in intracellular Ca(2+). In functional studies,
      isoproterenol inhibited U46619-induced platelet aggregation in a concentration
      dependent manner, but this effect was not significantly diminished by NOS
      inhibition. In contrast, thrombin-stimulated platelet adhesion to cultured human
      umbilical vein endothelial cell monolayers was inhibited by isoproterenol, and
      this effect was abolished by NOS inhibition (1.3+/-0.2% versus 2.6+/-0.2%
      respectively; P<0.001). Effects of isoproterenol on NOS activity, platelet
      aggregation, and adhesion were mediated exclusively through beta(2)ARs, as
      determined by coincubation with betaAR subtype-selective antagonists. We conclude
      that beta(2)ARs activate platelet NOS by increasing cAMP, and that this
      activation is Ca(2+)-independent. beta(2)ARs may contribute to modulation of
      platelet aggregation and adhesion to endothelium, and our findings suggest that
      activation of the L-arginine/NO system mediates the effects of beta(2)ARs on
      adhesion but not aggregation.

PMID- 10884371
TI  - Homocysteine thiolactone and protein homocysteinylation in human endothelial
      cells: implications for atherosclerosis.
AB  - Editing of the nonprotein amino acid homocysteine by certain aminoacyl-tRNA
      synthetases results in the formation of the thioester homocysteine thiolactone.
      Here we show that in the presence of physiological concentrations of
      homocysteine, methionine, and folic acid, human umbilical vein endothelial cells
      efficiently convert homocysteine to thiolactone. The extent of this conversion is
      directly proportional to homocysteine concentration and inversely proportional to
      methionine concentration, suggesting involvement of methionyl-tRNA synthetase.
      Folic acid inhibits the synthesis of thiolactone by lowering homocysteine and
      increasing methionine concentrations in endothelial cells. We also show that the
      extent of post-translational protein homocysteinylation increases with increasing
      homocysteine levels but decreases with increasing folic acid and HDL levels in
      endothelial cell cultures. These data support a hypothesis that metabolic
      conversion of homocysteine to thiolactone and protein homocysteinylation by
      thiolactone may play a role in homocysteine-induced vascular damage.

PMID- 10884372
TI  - Lysophosphatidylcholine activates p38 and p42/44 mitogen-activated protein
      kinases in monocytic THP-1 cells, but only p38 activation is involved in its
      stimulated chemotaxis.
AB  - Oxidized LDLs (OxLDLs) have been shown to be involved in recruitment of blood
      monocytes into the arterial subendothelial space, which is the earliest step in
      atherogenesis, but the underlying molecular mechanisms are poorly understood. The
      present study demonstrated that lysophosphatidylcholine (LPC), a major
      phospholipid component of OxLDL, strongly evoked phosphorylation and activation
      of p38 and p42/44 mitogen-activated protein kinases in monocytic cells. The
      stimulation of p38 and p42/44 occurred in a dose- and time-dependent manner,
      reaching the maximal activation at 25 microg/mL LPC within 5 minutes.
      Interestingly, inhibition of p38 activation by OxLDL or LPC, using its selective
      inhibitors (SB203580 and SKF86002), completely blocked OxLDL- or LPC-stimulated
      chemotaxis of THP-1 cells, which was measured in a transwell chemotaxis assay. In
      contrast, inhibition of p42/44 activation by its potent inhibitor (PD98059) did
      not block OxLDL- or LPC-stimulated chemotaxis. Moreover, expression of a p38
      dominant-negative mutant (p38AF) reduced cell chemotaxis significantly. In
      addition, activation of p38 by LPC was apparently mediated neither by scavenger
      receptors nor by tyrosine kinase receptors. It was, however, effectively blocked
      by pertussis toxin and substantially reduced by phospholipase C inhibitor
      (U73122) and phosphatidylinositol 3-kinase inhibitors (wortmannin and LY294002).
      LPC also inhibited forskolin-stimulated cAMP accumulation in a pertussis toxin
      sensitive manner, indicating that Gi/Go proteins likely mediated the effects of
      LPC. Our results suggested that OxLDL/LPC efficiently activated both p38 and
      p42/44, but only the activation of p38 was functionally associated with OxLDL
      /LPC-induced chemotaxis in THP-1 cells.

PMID- 10884373
TI  - Production of 20-HETE and its role in autoregulation of cerebral blood flow.
AB  - In the brain, pressure-induced myogenic constriction of cerebral arteriolar
      muscle contributes to autoregulation of cerebral blood flow (CBF). This study
      examined the role of 20-HETE in autoregulation of CBF in anesthetized rats. The
      expression of P-450 4A protein and mRNA was localized in isolated cerebral
      arteriolar muscle of rat by immunocytochemistry and in situ hybridization. The
      results of reverse transcriptase-polymerase chain reaction studies revealed that
      rat cerebral microvessels express cytochrome P-450 4A1, 4A2, 4A3, and 4A8
      isoforms, some of which catalyze the formation of 20-HETE from arachidonic acid.
      Cerebral arterial microsomes incubated with [(14)C]arachidonic acid produced 20
      HETE. An elevation in transmural pressure from 20 to 140 mm Hg increased 20-HETE
      concentration by 6-fold in cerebral arteries as measured by gas
      chromatography/mass spectrometry. In vivo, inhibition of vascular 20-HETE
      formation with N-methylsulfonyl-12, 12-dibromododec-11-enamide (DDMS), or its
      vasoconstrictor actions using 15-HETE or 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid
      (20-HEDE), attenuated autoregulation of CBF to elevations of arterial pressure.
      In vitro application of DDMS, 15-HETE, or 20-HEDE eliminated pressure-induced
      constriction of rat middle cerebral arteries, and 20-HEDE and 15-HETE blocked the
      vasoconstriction action of 20-HETE. Taken together, these data suggest an
      important role for 20-HETE in the autoregulation of CBF.

PMID- 10884374
TI  - FK409, a spontaneous nitric oxide releaser, attenuates allograft vasculopathy in
      a rat aortic transplant model.
AB  - Although systemic administration of NO donors has been shown to attenuate the
      development of neointimal hyperplasia in the balloon injury model, this strategy
      has not been tested in a model of allograft vasculopathy. In this study, we
      investigated the effect of FK409, a spontaneous NO releaser, on the development
      of allograft vasculopathy, using a rat aortic transplant model. Thoracic aortas
      from ACI rats were transplanted heterotopically into the abdominal aorta of
      Wistar-Furth rats. Postoperatively, recipients received FK409 orally every 8
      hours from the day of transplantation to the time of euthanization. Morphometric
      and immunohistochemical analyses were performed on the aortic grafts 8 weeks
      after transplantation. Control allografts showed severe neointimal hyperplasia,
      which consists mainly of alpha-actin-containing vascular smooth muscle cells. The
      FK409-treated allografts showed a dose-dependent reduction (statistically
      significant compared with the control) in the neointimal thickness as the dose
      increased from 1 to 10 mg/kg (thrice per day). However, there was no significant
      difference in the neointimal thickness between groups treated with 10 and with 20
      mg/kg. FK409 treatment (10 mg/kg) caused a significant decrease in DNA synthesis
      (5-bromo-2-deoxyuridine [BrdU] uptake), an increase in DNA fragmentation
      (terminal deoxynucleotidyltransferase-mediated uridine nick-end labeling
      [TUNEL]), and upregulation of Fas expression, in the neointimal vascular smooth
      muscle cells. These data suggest that FK409 attenuates the allograft vasculopathy
      in a rat aortic transplant model.

PMID- 10884375
TI  - Functional consequences of elimination of i(to,f) and i(to,s): early
      afterdepolarizations, atrioventricular block, and ventricular arrhythmias in mice
      lacking Kv1.4 and expressing a dominant-negative Kv4 alpha subunit.
AB  - It was recently reported that the slow transient outward K(+) current, I(to, s),
      that is evident in mouse left ventricular septal cells is eliminated in mice with
      a targeted deletion of the Kv1.4 gene (Kv1.4(-/-)). The rapidly inactivating
      transient outward K(+) current, I(to, f), in contrast, is selectively eliminated
      in ventricular myocytes isolated from transgenic mice expressing a dominant
      negative Kv4 alpha subunit, Kv4.2W362F. Expression of Kv4. 2W362F results in
      marked prolongation of action potentials and QT intervals. In addition, a slow
      transient outward K(+) current, that is similar to I(to,s) in wild-type mouse
      left ventricular septal cells, is evident in all Kv4.2W362F-expressing (left and
      right) ventricular cells. To test directly the hypothesis that upregulation of
      Kv1.4 alpha subunit underlies the appearance of this slow transient outward K(+)
      current in Kv4.2W362F-expressing ventricular cells and to explore the functional
      consequences of elimination of I(to,f) and I(to,s), mice expressing Kv4.2W362F in
      the Kv1.4(-/-) background (Kv4.2W362FxKv1.4(-/-)) were generated. Histological
      and echocardiographic studies revealed no evidence of structural abnormalities or
      contractile dysfunction in Kv4.2W362FxKv1.4(-/-) mouse hearts.
      Electrophysiological recordings from the majority (approximately 80%) of cells
      isolated from the right ventricle and left ventricular apex of Kv4.2W362FxKv1.4(
      /-) animals demonstrated that both I(to, f) and I(to,s) are eliminated; action
      potentials are prolonged significantly; and, in some cells, early
      afterdepolarizations were observed. In addition, in vivo telemetric ECG
      recordings from Kv4.2W362FxKv1.4(-/-) animals revealed marked QT prolongation,
      atrioventricular block, and ventricular tachycardia. These observations
      demonstrate that upregulation of Kv1.4 contributes to the electrical remodeling
      evident in the ventricles of Kv4.2W362F-expressing mice and that elimination of
      both I(to,f) and I(to,s) has dramatic functional consequences.

PMID- 10884376
TI  - Patched target Igf2 is indispensable for the formation of medulloblastoma and
      rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children
      (Dagher, R., and Helman, L. (1999) Oncologist 4, 34-44), whereas medulloblastoma,
      a highly malignant tumor of the cerebellum, accounts for 20% of childhood brain
      tumors (Goodrich, L. V., and Scott, M. P. (1998) Neuron 21, 1243-1257). Both
      tumors are associated with a deficiency in the tumor suppressor Patched (PTCH) in
      Gorlin syndrome (Gorlin, R. J. (1987) Medicine (Baltimore) 66, 98-113), and they
      are present in the corresponding murine models. RMS in Ptch mutant mice
      consistently contain elevated levels of the tumor growth-promoting insulin-like
      growth factor 2 (Igf2). We have investigated the mechanism of Igf2 overexpression
      and its significance in medulloblastoma and RMS tumorigenesis. Here we report
      that Igf2 is indispensable for the formation of medulloblastoma and RMS in Ptch
      mutants. Overexpression of Igf2 in RMS in these mice does not involve loss of
      imprinting, uniparental disomy, amplification of the Igf2 locus, or polyploidy.
      Since Igf2 is also overexpressed in non-tumor tissue deficient in Ptch, these
      observations suggest that Ptch regulates Igf2 levels through a transcriptional
      mechanism. They also identify Igf2 as a potential target for medulloblastoma and
      RMS.

PMID- 10884377
TI  - Regulation of cyclooxygenase-2 and periostin by Wnt-3 in mouse mammary epithelial
      cells.
AB  - Wnt family members are critical in developmental processes and have been shown to
      promote carcinogenesis when ectopically expressed in the mouse mammary gland. The
      gene expression pattern mediated by Wnt is pivotal for these diverse responses.
      The Wnt pathway has been conserved among different species. Genetic studies have
      shown that Wnt effects are mediated, at least in part, by beta-catenin, which
      regulates transcription of "downstream genes." Wnt stimulation inactivates
      glycogen-synthase kinase-3beta (GSK-3) with subsequent stabilization of beta
      catenin, which after heterodimerizing with lymphocyte enhancer factor-1/T-cell
      factor cofactors stimulates transcription. To establish whether Wnt-stimulated
      transcription is mediated solely by beta-catenin, a comparison was made of gene
      expression profiles in response to Wnt-3, overexpression of beta-catenin, and
      inhibition of GSK-3. Infection of cells with Wnt-3 and inhibition of GSK-3
      regulate a set of genes that include cyclooxygenase-2 and periostin.
      Interestingly, overexpression of beta-catenin or reducing beta-catenin levels
      with antisense oligonucleotide transfection did not have any effect on
      cyclooxygenase-2 or periostin expression, thereby defining a Wnt pathway, which
      cannot be mimicked by beta-catenin overexpression.

PMID- 10884378
TI  - Phosphorylation by cyclin-dependent protein kinase 5 of the regulatory subunit of
      retinal cGMP phosphodiesterase. I. Identification of the kinase and its role in
      the turnoff of phosphodiesterase in vitro.
AB  - Cyclic GMP phosphodiesterase (PDE) is an essential component in retinal
      phototransduction. PDE is regulated by Pgamma, the regulatory subunit of PDE, and
      GTP/Talpha, the GTP-bound alpha subunit of transducin. In previous studies
      (Tsuboi, S., Matsumoto, H. , Jackson, K. W., Tsujimoto, K., Williamas, T., and
      Yamazaki, A. (1994) J. Biol. Chem. 269, 15016-15023; Tsuboi, S., Matsumoto, H.,
      and Yamazaki, A. (1994) J. Biol. Chem. 269, 15024-15029), we showed that Pgamma
      is phosphorylated by a previously unknown kinase (Pgamma kinase) in a GTP
      dependent manner in photoreceptor outer segment membranes. We also showed that
      phosphorylated Pgamma loses its ability to interact with GTP/Talpha, but gains a
      10-15 times higher ability to inhibit GTP/Talpha-activated PDE than that of
      nonphosphorylated Pgamma. Thus, we propose that the Pgamma phosphorylation is
      probably involved in the recovery phase of phototransduction through shut off of
      GTP/Talpha-activated PDE. Here we demonstrate that all known Pgammas preserve a
      consensus motif for cyclin-dependent protein kinase 5 (Cdk5), a protein kinase
      believed to be involved in neuronal cell development, and that Pgamma kinase is
      Cdk5 complexed with p35, a neuronal Cdk5 activator. Mutational analysis of Pgamma
      indicates that all known Pgammas contain a P-X-T-P-R sequence and that this
      sequence is required for the Pgamma phosphorylation by Pgamma kinase. In three
      different column chromatographies of a cytosolic fraction of frog photoreceptor
      outer segments, the Pgamma kinase activity exactly coelutes with Cdk5 and p35.
      The Pgamma kinase activity ( approximately 85%) is also immunoprecipitated by a
      Cdk5-specific antibody, and the immunoprecipitate phosphorylates Pgamma. Finally,
      recombinant Cdk5/p35, which were expressed using clones from a bovine retina cDNA
      library, phosphorylates Pgamma in frog outer segment membranes in a GTP-dependent
      manner. These observations suggest that Cdk5 is probably involved in the recovery
      phase of phototransduction through phosphorylation of Pgamma complexed with
      GTP/Talpha in mature vertebrate retinal photoreceptors.

PMID- 10884379
TI  - Phosphorylation by cyclin-dependent protein kinase 5 of the regulatory subunit of
      retinal cGMP phosphodiesterase. II. Its role in the turnoff of phosphodiesterase
      in vivo.
AB  - Retinal cGMP phosphodiesterase (PDE) is regulated by Pgamma, the regulatory
      subunit of PDE, and GTP/Talpha, the GTP-bound alpha subunit of transducin. In the
      accompanying paper (Matsuura, I., Bondarenko, V. A., Maeda, T., Kachi, S.,
      Yamazaki, M., Usukura, J., Hayashi, F., and Yamazaki, A. (2000) J. Biol. Chem.
      275, 32950-32957), we have shown that all known Pgammas contain a specific
      phosphorylation motif for cyclin-dependent protein kinase 5 (Cdk5) and that the
      unknown kinase is Cdk5 complexed with its activator. Here, using frog rod
      photoreceptor outer segments (ROS) isolated by a new method, we show that Cdk5 is
      involved in light-dependent Pgamma phosphorylation in vivo. Under dark conditions
      only negligible amounts of Pgamma were phosphorylated. However, under
      illumination that bleached less than 0.3% of the rhodopsin, approximately 4% of
      the total Pgamma was phosphorylated in less than 10 s. Pgamma dephosphorylation
      occurred in less than 1 s after the light was turned off. Analysis of the
      phosphorylated amino acid, inhibition of Pgamma phosphorylation by Cdk inhibitors
      in vivo and in vitro, and two-dimensional peptide map analysis of Pgamma
      phosphorylated in vivo and in vitro indicate that Cdk5 phosphorylates a Pgamma
      threonine in the same manner in vivo and in vitro. These observations, together
      with immunological data showing the presence of Cdk5 in ROS, suggest that Cdk5 is
      involved in light-dependent Pgamma phosphorylation in ROS and that the
      phosphorylation is significant and reversible. In an homogenate of frog ROS, PDE
      activated by light/guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) was inhibited
      by Pgamma alone, but not by Pgamma complexed with GDP/Talpha or GTPgammaS/Talpha.
      Under these conditions, Pgamma phosphorylated by Cdk5 inhibited the
      light/GTPgammaS-activated PDE even in the presence of GTPgammaS/Talpha. These
      observations suggest that phosphorylated Pgamma interacts with and inhibits
      light/GTPgammaS-activated PDE, but does not interact with GTPgammaS/Talpha in the
      homogenate. Together, our results strongly suggest that after activation of PDE
      by light/GTP, Pgamma is phosphorylated by Cdk5 and the phosphorylated Pgamma
      inhibits GTP/Talpha-activated PDE, even in the presence of GTP/Talpha in ROS.

PMID- 10884380
TI  - Characterization of the interaction of calcyclin (S100A6) and calcyclin-binding
      protein.
AB  - Calcyclin (S100A6) is an S100 calcium-binding protein whose expression is up
      regulated in proliferating and differentiating cells. A novel 30-kDa protein
      exhibiting calcium-dependent calcyclin-binding (calcyclin-binding protein,
      CacyBP) had been identified, purified, and cloned previously (Filipek, A., and
      Kuznicki, J. (1998) J. Neurochem. 70, 1793-1798). Here, we have defined the
      calcyclin binding region using limited proteolysis and a set of deletion mutants
      of CacyBP. A fragment encompassing residues 178-229 (CacyBP-(178-229)) was
      capable of full binding to calcyclin. CacyBP-(178-229) was expressed in
      Escherichia coli as a glutathione S-transferase fusion protein and purified. The
      protein fragment cleaved from the glutathione S-transferase fusion protein was
      shown by CD to contain 5% alpha-helix, 15% beta -sheet, and 81% random coil.
      Fluorescence spectroscopy was used to determine calcyclin dissociation constants
      of 0.96 and 1.2 microm for intact CacyBP and CacyBP-(178-229), respectively,
      indicating that the fragment can be used for characterization of calcyclin-CacyBP
      interactions. NMR analysis of CacyBP-(178-229) binding-induced changes in the
      chemical shifts of (15)N-enriched calcyclin revealed that CacyBP binding occurs
      at a discrete site on calcyclin with micromolar affinity.

PMID- 10884381
TI  - Phosphorylation of phosducin and phosducin-like protein by G protein-coupled
      receptor kinase 2.
AB  - G protein-coupled receptor kinase 2 (GRK2) is able to phosphorylate a variety of
      agonist-occupied G protein-coupled receptors (GPCR) and plays an important role
      in GPCR modulation. However, recent studies suggest additional cellular functions
      for GRK2. Phosducin and phosducin-like protein (PhLP) are cytosolic proteins that
      bind Gbetagamma subunits and act as regulators of G-protein signaling. In this
      report, we identify phosducin and PhLP as novel GRK2 substrates. The
      phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds
      rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P(i)/mol of
      protein, respectively). The phosphorylation reactions exhibit apparent K(m)
      values in the range of 40-100 nm, strongly suggesting that both proteins could be
      endogenous targets for GRK2 activity. Our data show that the site of phosducin
      phosphorylation by GRK2 is different and independent from that previously
      reported for the cAMP-dependent protein kinase. Analysis of GRK2 phosphorylation
      of a variety of deletion mutants of phosducin and PhLP indicates that the
      critical region for GRK2 phosphorylation is localized in the C-terminal domain of
      both phosducin and PhLP (between residues 204 and 245 and 195 and 218,
      respectively). This region is important for the interaction of these proteins
      with G beta gamma subunits. Phosphorylation of phosducin by GRK2 markedly reduces
      its G beta gamma binding ability, suggesting that GRK2 may modulate the activity
      of the phosducin protein family by disrupting this interaction. The
      identification of phosducin and PhLP as new substrates for GRK2 further expands
      the cellular roles of this kinase and suggests new mechanisms for modulating GPCR
      signal transduction.

PMID- 10884382
TI  - Caspase 3-mediated cleavage of p21WAF1/CIP1 associated with the cyclin A-cyclin
      dependent kinase 2 complex is a prerequisite for apoptosis in SK-HEP-1 cells.
AB  - Apoptosis of SK-HEP-1 human hepatoma cells induced by treatment with ginsenoside
      Rh2 (G-Rh2) is associated with rapid and selective activation of cyclin A
      associated cyclin-dependent kinase 2 (Cdk2). Here, we show that in apoptotic
      cells, the Cdk inhibitory protein p21(WAF1/CIP1), which is associated with the
      cyclin A-Cdk2 complex, undergoes selective proteolytic cleavage. In contrast,
      another Cdk inhibitory protein, p27(KIP1), which is associated with cyclin A-Cdk2
      and cyclin E-Cdk2 complexes, remained unaltered during apoptosis. Ectopic
      overexpression of p21(WAF1/CIP1) suppressed apoptosis as well as cyclin A-Cdk2
      activity induced by treatment of SK-HEP-1 cells with G-Rh2. The suppressive
      effects of p21(WAF1/CIP1) were much higher in the cells transfected with
      p21D112N, an expression vector that encodes a p21(WAF1/CIP1) mutant resistant to
      caspase 3 cleavage. Overexpression of cyclin A in SK-HEP-1 cells dramatically up
      regulated cyclin A-Cdk2 activity and accordingly enhances apoptosis induced by
      treatment with G-Rh2. These up-regulating effects were blocked by coexpression of
      a dominant negative allele of cdk2. Furthermore, olomoucine, a specific inhibitor
      of Cdks, also blocked G-Rh2-induced apoptosis. These data suggest that the
      induction of apoptosis in human hepatoma cells treated with G-Rh2 occurs by a
      mechanism that involves the activation of cyclin A-Cdk2 by caspase 3-mediated
      cleavage of p21(WAF1/CIP1).

PMID- 10884383
TI  - Substrate specificity and reaction mechanism of murine 8-oxoguanine-DNA
      glycosylase.
AB  - Genomic DNA is prone to oxidation by reactive oxygen species. A major product of
      DNA oxidation is the miscoding base 8-oxoguanine (8-oxoG). The mutagenic effects
      of 8-oxoG in mammalian cells are prevented by a DNA repair system consisting of 8
      oxoguanine-DNA glycosylase (Ogg1), adenine-DNA glycosylase, and 8-oxo-dGTPase. We
      have cloned, overexpressed, and characterized mOgg1, the product of the murine
      ogg1 gene. mOgg1 is a DNA glycosylase/AP lyase belonging to the endonuclease III
      family of DNA repair enzymes. The AP lyase activity of mOgg1 is significantly
      lower than its glycosylase activity. mOgg1 releases 8-oxoG from DNA when paired
      with C, T, or G, but efficient DNA strand nicking is observed only with 8-oxoG:C.
      Binding of mOgg1 to oligonucleotides containing 8-oxoG:C is strong (K(D) = 51.5
      nm), unlike other mispairs. The average residence time for mOgg1 bound to
      substrate containing 8-oxoG:C is 18.3 min; the time course for accumulation of
      the NaBH(4)-sensitive intermediate suggests a two-step reaction mechanism.
      Various analogs of 8-oxoG were tested as substrates for mOgg1. An electron
      withdrawing or hydrogen bond acceptor moiety at C8 is required for efficient
      binding of mOgg1. A substituent at C6 and a keto group at C8 are required for
      cleavage. The proposed mechanism of 8-oxoG excision involves protonation of O(8)
      or the deoxyribose oxygen moiety.

PMID- 10884384
TI  - Increase in plasma homocysteine associated with parallel increases in plasma S
      adenosylhomocysteine and lymphocyte DNA hypomethylation.
AB  - S-Adenosylmethionine and S-adenosylhomocysteine (SAH), as the substrate and
      product of essential cellular methyltransferase reactions, are important
      metabolic indicators of cellular methylation status. Chronic elevation of SAH,
      secondary to the homocysteine-mediated reversal of the SAH hydrolase reaction,
      reduces methylation of DNA, RNA, proteins, and phospholipids. High affinity
      binding of SAH to the active site of cellular methyltransferases results in
      product inhibition of the enzyme. Using a sensitive new high pressure liquid
      chromatography method with coulometric electrochemical detection, plasma SAH
      levels in healthy young women were found to increase linearly with mild elevation
      in homocysteine levels (r = 0.73; p < 0.001); however, S-adenosylmethionine
      levels were not affected. Plasma SAH levels were positively correlated with
      intracellular lymphocyte SAH levels (r = 0.81; p < 0.001) and also with
      lymphocyte DNA hypomethylation (r = 0.74, p < 0.001). These results suggest that
      chronic elevation in plasma homocysteine levels, such as those associated with
      nutritional deficiencies or genetic polymorphisms in the folate pathway, may have
      an indirect and negative effect on cellular methylation reactions through a
      concomitant increase in intracellular SAH levels.

PMID- 10884385
TI  - Raf-1/MEK/MAPK pathway is necessary for the G2/M transition induced by
      nocodazole.
AB  - The dynamic balance between polymerization and depolymerization of microtubules
      is critical for cells to enter and exit mitosis, and drugs that disrupt this
      balance, such as taxol, colchicine, and nocodazole, arrest the cell cycle in
      mitosis. Although the Raf/MEK/MAPK pathway can be activated by these drugs, its
      role in mitosis has not been addressed. Here, we characterize activation of
      Raf/MEK/MAPK by nocodazole when mitosis is induced. We find that at early time
      points (up to 3 h) in nocodazole induction, Raf/MEK/MAPK is activated, and
      inhibition of MAPK activation by a MEK inhibitor, PD98059 or U0126, reduces the
      number of cells entering mitosis by creating a block at G(2). At later time
      points and in mitosis, activation of MEK/MAPK is severely inhibited, even though
      Raf-1 activity remains high and can be further increased by growth factor. This
      inhibition is reversed when cells are released from metaphase and enter G(0)/G(1)
      phase. In addition, we find that binding of Raf-1 to 14-3-3 is progressively
      induced by nocodazole, reaching a maximum in mitosis, and that this binding is
      necessary to maintain mitotic Raf-1 activity. Our present study indicates that
      activation of the Raf/MEK/MAPK pathway is necessary for the G(2)/M progression.

PMID- 10884386
TI  - The crystal structure of nitrophorin 2. A trifunctional antihemostatic protein
      from the saliva of Rhodnius prolixus.
AB  - Nitrophorin 2 (NP2) (also known as prolixin-S) is a salivary protein that
      transports nitric oxide, binds histamine, and acts as an anticoagulant during
      blood feeding by the insect Rhodnius prolixus. The 2.0-A crystal structure of NP2
      reveals an eight-stranded antiparallel beta-barrel containing a ferric heme
      coordinated through His(57), similar to the structures of NP1 and NP4. All four
      Rhodnius nitrophorins transport NO and sequester histamine through heme binding,
      but only NP2 acts as an anticoagulant. Here, we demonstrate that recombinant NP2,
      but not recombinant NP1 or NP4, is a potent anticoagulant; recombinant NP3 also
      displays minor activity. Comparison of the nitrophorin structures suggests that a
      surface region near the C terminus and the loops between beta strands B-C and E-F
      is responsible for the anticoagulant activity. NP2 also displays larger NO
      association rates and smaller dissociation rates than NP1 and NP4, which may
      result from a more open and more hydrophobic distal pocket, allowing more rapid
      solvent reorganization on ligand binding. The NP2 protein core differs from NP1
      and NP4 in that buried Glu(53), which allows for larger NO release rates when
      deprotonated, hydrogen bonds to invariant Tyr(81). Surprisingly, this tyrosine
      lies on the protein surface in NP1 and NP4.

PMID- 10884387
TI  - Regulation of the yeast transcriptional factor PHO2 activity by phosphorylation.
AB  - The induction of yeast Saccharomyces cerevisiae gene PHO5 expression is mediated
      by transcriptional factors PHO2 and PHO4. PHO4 protein has been reported to be
      phosphorylated and inactivated by a cyclin-CDK (cyclin-dependent kinase) complex,
      PHO80-PHO85. We report here that PHO2 can also be phosphorylated. A Ser-230 to
      Ala mutation in the consensus sequence (SPIK) recognized by cdc2/CDC28-related
      kinase in PHO2 protein led to complete loss of its ability to activate the
      transcription of PHO5 gene. Further investigation showed that the Pro-231 to Ser
      mutation inactivated PHO2 protein as well, whereas the Ser-230 to Asp mutation
      did not affect PHO2 activity. Since the PHO2 Asp-230 mutant mimics Ser-230
      phosphorylated PHO2, we postulate that only phosphorylated PHO2 protein could
      activate the transcription of PHO5 gene. Two hybrid assays showed that yeast
      CDC28 could interact with PHO2. CDC28 immunoprecipitate derived from the YPH499
      strain grown under low phosphate conditions phosphorylated GST-PHO2 in vitro. A
      phosphate switch regulates the transcriptional activation activity of PHO2, and
      mutations of the (SPIK) site affect the transcriptional activation activity of
      PHO2 and the interaction between PHO2 and PHO4. BIAcore(R) analysis indicated
      that the negative charge in residue 230 of PHO2 was sufficient to help PHO2
      interact with PHO4 in vitro.

PMID- 10884388
TI  - Local structural elements in the mostly unstructured transcriptional activation
      domain of human p53.
AB  - DNA transcription is initiated by a small regulatory region of transactivators
      known as the transactivation domain. In contrast to the rapid progress made on
      the functional aspect of this promiscuous domain, its structural feature is still
      poorly characterized. Here, our multidimensional NMR study reveals that an
      unbound full-length p53 transactivation domain, although similar to the recently
      discovered group of loosely folded proteins in that it does not have tertiary
      structure, is nevertheless populated by an amphipathic helix and two nascent
      turns. The helix is formed by residues Thr(18)-Leu(26) (Thr-Phe-Ser-Asp-Leu-Trp
      Lys-Leu-Leu), whereas the two turns are formed by residues Met(40)-Met(44) and
      Asp(48)-Trp(53), respectively. It is remarkable that these local secondary
      structures are selectively formed by functionally critical and positionally
      conserved hydrophobic residues present in several acidic transactivation domains.
      This observation suggests that such local structures are general features of
      acidic transactivation domains and may represent "specificity determinants"
      (Ptashne, M., and Gann, A. A. F. (1997), Nature 386, 569-577) that are important
      for transcriptional activity.

PMID- 10884389
TI  - Repression of BRCA1 through a feedback loop involving p53.
AB  - The BRCA1 and p53 tumor suppressors have been shown to interact and cooperate to
      activate transcription of p53-responsive genes. In this study, we show that BRCA1
      is initially up-regulated, followed by a reduction to below basal levels in
      response to treatment with the DNA-damaging agents adriamycin and mitomycin C,
      and that the reduction of BRCA1 expression is dependent on the presence of wild
      type p53. Elimination of p53 by expression of human papilloma virus E6 resulted
      in an inability to down-regulate BRCA1 in response to adriamycin. Ectopic
      expression of p53 resulted in a rapid decrease in BRCA1 protein and RNA levels
      and BRCA1 promoter-driven luciferase activity even in null p21 cells deficient in
      p53-dependent G(1) arrest. ATM(-)(/-) lymphoblastoid cells were deficient in
      their ability to reduce BRCA1 protein in response to DNA damage, whereas the wild
      type counterparts reduced BRCA1 protein levels after exposure to adriamycin.
      These results, in conjunction with others, suggest a loop wherein BRCA1 initially
      participates in accumulation of p53 protein, whereas later p53 acts to reduce
      BRCA1 expression.

PMID- 10884390
TI  - Physical and functional interaction between p53 mutants and different isoforms of
      p73.
AB  - p53 is the most frequently inactivated tumor suppressor gene in human cancer,
      whereas its homologue, p73, is rarely mutated. Similarly to p53, p73 can promote
      growth arrest or apoptosis when overexpressed in certain p53-null tumor cells. It
      has previously been shown that some human tumor-derived p53 mutants can exert
      gain of function activity. The molecular mechanism underlying this activity
      remains to be elucidated. We show here that human tumor-derived p53 mutants
      (p53His175 and p53Gly281) associate in vitro and in vivo with p73 alpha, beta,
      gamma, and delta. This association occurs under physiological conditions, as
      verified in T47D and SKBR3 breast cancer cell lines. The core domain of mutant
      p53 is sufficient for the association with p73, whereas both the specific DNA
      binding and the oligomerization domains of p73 are required for the association
      with mutant p53. Furthermore, p53His175 and p53Gly281 mutants markedly reduce the
      transcriptional activity of the various isoforms of p73. Thus, human tumor
      derived p53 mutants can associate with p73 not only physically but also
      functionally. These findings define a network involving mutant p53 and the
      various spliced isoforms of p73 that may confer upon tumor cells a selective
      survival advantage.

PMID- 10884391
TI  - Hormone interactions to Leu-rich repeats in the gonadotropin receptors. II.
      Analysis of Leu-rich repeat 4 of human luteinizing hormone/chorionic gonadotropin
      receptor.
AB  - The luteinizing hormone receptor (LHR) consists of an approximately 350-amino
      acid-long N-terminal extracellular exodomain and a membrane-associated endodomain
      of similar size. Human chorionic gonadotropin (hCG) binds to the exodomain, and
      then hCG/exodomain complex is thought to make a secondary contact with the
      endodomain and generate hormone signals. The sequence alignment of the exodomain
      shows imperfectly matching eight to nine Leu-rich repeats (LRRs). In the
      preceding article (Song, Y., Ji, I., Beauchamp, J., Isaacs, N., and Ji, T. (2001)
      J. Biol. Chem. 276, 3426-3435), we have shown that LRR2 and LRR4 are crucial for
      hormone binding. In this work, we have examined the residues of LRR4, in
      particular Leu(103) and Ile(105) in the putative beta strand. Our data show that
      Leu(103) and Ile(105) are involved in the specific, hydrophobic interaction of
      the LRR4 loop, likely to form the hydrophobic core. This loop is crucial for the
      structural integrity of all of the LRRs. In contrast, the downstream sequence
      consisting of Asn(107), Thr(108), Gly(109), and Ile(110) of LRR4 is crucial for
      cAMP induction but not for hormone binding, folding, and surface expression. This
      implicates, for the first time, its involvement in the interaction with the
      endodomain and signal generation. The evidence for the interaction is presented
      in the following article.

PMID- 10884392
TI  - Endocytosis of insulin-like growth factor II by a mini-receptor based on repeat
      11 of the mannose 6-phosphate/insulin-like growth factor II receptor.
AB  - The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-II
      receptor) plays an important role in controlling the extracellular level of the
      insulin-like growth factor II (IGF-II) by mediating its binding at the cell
      surface and delivery to lysosomes. Loss of the receptor is associated with an
      accumulation of IGF-II, which can cause perinatal lethality if it is systemic, or
      local proliferation and tumorgenesis if it is spatially restricted. The
      extracytoplasmic domain of the receptor consists of 15 homologous repeats, of
      which repeat 11 carries the IGF-II-binding site of the multifunctional receptor.
      To investigate whether repeat 11 is sufficient to mediate binding and
      internalization of IGF-II, a construct consisting of repeat 11 fused to the
      transmembrane and cytoplasmic domain of the M6P/IGF-II receptor was transfected
      into mouse embryonic fibroblasts. The construct was expressed as a stable
      membrane protein which binds IGF-II with a 10-fold lower affinity as observed for
      the M6P/IGF-II receptor and is found at the cell surface and in endosomes. It
      mediates the internalization of IGF-II and its delivery to lysosomes, suggesting
      that it can function as a IGF-II mini-receptor controlling the extracellular IGF
      II level.

PMID- 10884393
TI  - Covalent heterogeneity of the human enzyme galactose-1-phosphate
      uridylyltransferase.
AB  - Galactose-1-phosphate uridylyltransferase (GALT) acts by a double displacement
      mechanism, catalyzing the second step in the Leloir pathway of galactose
      metabolism. Impairment of this enzyme results in the potentially lethal disorder,
      galactosemia. Although the microheterogeneity of native human GALT has long been
      recognized, the biochemical basis for this heterogeneity has remained obscure. We
      have explored the possibility of covalent GALT heterogeneity using denaturing two
      dimensional gel electrophoresis and Western blot analysis to fractionate and
      visualize hemolysate hGALT, as well as the human enzyme expressed in yeast. In
      both contexts, two predominant GALT species were observed. To define the
      contribution of uridylylated enzyme intermediate to the two-spot pattern, we
      exploited the null allele, H186G-hGALT. The Escherichia coli counterpart of this
      mutant protein (H166G-eGALT) has previously been demonstrated to fold properly,
      although it cannot form covalent intermediate. Analysis of the H186G-hGALT
      protein demonstrated a single predominant species, implicating covalent
      intermediate as the basis for the second spot in the wild-type pattern. In
      contrast, three naturally occurring mutations, N314D, Q188R, and S135L-hGALT, all
      demonstrated the two-spot pattern. Together, these data suggest that uridylylated
      hGALT comprises a significant fraction of the total GALT enzyme pool in normal
      human cells and that three of the most common patient mutations do not disrupt
      this distribution.

PMID- 10884394
TI  - Cross-talk between the allosteric effector-binding sites in mouse ribonucleotide
      reductase.
AB  - We compared the allosteric regulation and effector binding properties of wild
      type R1 protein and R1 protein with a mutation in the "activity site" (D57N) of
      mouse ribonucleotide reductase. Wild type R1 had two effector-binding sites per
      polypeptide chain: one site (activity site) for dATP and ATP, with dATP
      inhibiting and ATP-stimulating catalytic activity; and a second site (specificity
      site) for dATP, ATP, dTTP, and dGTP, directing substrate specificity. Binding of
      dATP to the specificity site had a 20-fold higher affinity than to the activity
      site. In all these respects, mouse R1 resembles Escherichia coli R1. Results with
      D57N were complicated by the instability of the protein, but two major changes
      were apparent. First, enzyme activity was stimulated by both dATP and ATP,
      suggesting that D57N no longer distinguished between the two nucleotides. Second,
      the two binding sites for dATP both had the same low affinity for the nucleotide,
      similar to that of the activity site of wild type R1. Thus the mutation in the
      activity site had decreased the affinity for dATP at the specificity site,
      demonstrating the interaction between the two sites.

PMID- 10884395
TI  - The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1,
      hHus1, and hRad9.
AB  - DNA damage activates cell cycle checkpoints that prevent progression through the
      cell cycle. In yeast, the DNA damage checkpoint response is regulated by a series
      of genes that have mammalian homologs, including rad1, rad9, hus1, and rad17. On
      the basis of sequence homology, yeast and human Rad1, Rad9, and Hus1 protein
      homologs are predicted to structurally resemble the sliding clamp PCNA. Likewise,
      Rad17 homologs have extensive homology with replication factor C (RFC) subunits
      (p36, p37, p38, p40, and p140), which form a clamp loader for PCNA. These
      observations predict that Rad1, Hus1, and Rad9 might interact with Rad17 as a
      clamp-clamp loader pair during the DNA damage response. In this report, we
      demonstrate that endogenous human Rad17 (hRad17) interacts with the PCNA-related
      checkpoint proteins hRad1, hRad9, and hHus1. Mutational analysis of hRad1 and
      hRad17 demonstrates that this interaction has properties similar to the
      interaction between RFC and PCNA, a well characterized clamp-clamp loader pair.
      Moreover, we show that DNA damage affects the association of hRad17 with the
      clamp-like checkpoint proteins. Collectively, these data provide the first
      experimental evidence that hRad17 interacts with the PCNA-like proteins hRad1,
      hHus1, and hRad9 in manner similar to the interaction between RFC and PCNA.

PMID- 10884396
TI  - Transforming growth factor beta contributes to progressive diabetic nephropathy.

PMID- 10884397
TI  - Anfinsen comes out of the cage during assembly of the bacterial pilus.

PMID- 10884398
TI  - Schizophrenia: more dopamine, more D2 receptors.

PMID- 10884399
TI  - Production of resistant HIV mutants during antiretroviral therapy.
AB  - HIV drug therapy often fails because of the appearance of multidrug-resistant
      virus. There are two possible scenarios for the outgrowth of multidrug-resistant
      virus in response to therapy. Resistant virus may preexist at low frequencies in
      drug-naive patients and is rapidly selected in the presence of drugs.
      Alternatively, resistant virus is absent at the start of therapy but is generated
      by residual viral replication during therapy. Currently available experimental
      methods are generally too insensitive to distinguish between these two scenarios.
      Here we use deterministic and stochastic models to investigate the origin of
      multidrug resistance. We quantify the probabilities that resistant mutants
      preexist, and that resistant mutants are generated during therapy. The models
      suggest that under a wide range of conditions, treatment failure is most likely
      caused by the preexistence of resistant mutants.

PMID- 10884400
TI  - Mimicking the antenna-electron transfer properties of photosynthesis.
AB  - A molecular assembly based on derivatized polystyrene is described, which mimics
      both the light-harvesting and energy-conversion steps of photosynthesis. The
      system is unique in that the two key parts of a photosynthetic system are
      incorporated in a functional assembly constructed from polypyridine complexes of
      Ru(II). This system is truly artificial, as none of the components used in
      construction of the assembly are present in a natural photosynthetic system.
      Quantitative evaluation of the energy and electron transfer dynamics after
      transient irradiation by visible light offers important insights into the
      mechanisms of energy transport and electron transfer that lead to photosynthetic
      light-to-chemical energy conversion.

PMID- 10884401
TI  - Euclidean shape-encoded combinatorial chemical libraries.
AB  - A method for the encoding of split/mix combinatorial chemical libraries based on
      Euclidean shapes is described. The shapes are fashioned from a polymeric matrix
      designed to swell in common organic solvents while retaining their unique forms,
      and exhibit good mechanical strength. The lightly crosslinked gel-type polymer
      was processed into an array of Euclidean forms that serve as encoding elements in
      the synthesis of combinatorial chemical libraries by using the split/pool
      methodology. To assess the viability of this approach, a library of compounds
      based on a urea scaffold was prepared. The validity of this methodology was
      demonstrated through correct deconvolution of the library mixture by shape
      discrimination. Furthermore, because the shapes used have a large surface area to
      volume ratio, each monolith can act as an independent chemical reactor. This
      simplifies the analytical identification process because each compound can be
      prepared in significant quantities and isolated as single entities. Given the
      high loading capacity of the monoliths and the conceptually simple encoding
      strategy, it is envisioned that these Euclidean forms will find significant
      application in combinatorial and high-throughput synthetic chemistry.

PMID- 10884402
TI  - A pseudo zeta function and the distribution of primes.
AB  - The Riemann zeta function is given by: [equation, see published text]. Zeta(s)
      may be analytically continued to the entire s-plane, except for a simple pole at
      s = 0. Of great interest are the complex zeros of zeta(s). The Riemann hypothesis
      states that the complex zeros all have real part 1/2. According to the prime
      number theorem, pn approximately n logn, where pn is the nth prime. Suppose that
      pn were exactly nlogn. In other words, in the Euler product above, replace the
      nth prime by nlogn. In this way, we define a pseudo zeta function C(s) for Re s >
      1. One can show that C(s) may be analytically continued at least into the half
      plane Re s > 0 except for an isolated singularity (presumably a simple pole) at s
      = 0. It may be shown that the pseudo zeta function C(s) has no complex zeros
      whatsoever. This means that the complex zeros of the zeta function are associated
      with the irregularity of the distribution of the primes.

PMID- 10884403
TI  - The protelomerase of temperate Escherichia coli phage N15 has cleaving-joining
      activity.
AB  - Escherichia coli phage N15 encodes the slightly acidic, 630-residue protein of
      72.2 kDa called protelomerase (TelN). TelN is a component of the N15 replication
      system proposed to be involved in the generation of the linear prophage DNA. This
      linear DNA molecule has covalently closed ends. The reaction converting circular
      plasmids into linear molecules was catalyzed in vitro. We demonstrate that the
      product of telN functions as the protelomerase in the absence of other N15
      encoded factors. Purified TelN processes circular and linear plasmid DNA
      containing the proposed target site telRL to produce linear double-stranded DNA
      with covalently closed ends. The 56-bp telRL target site consists of a central
      telO palindrome of 22 bp and two 14-bp flanking sequences comprising inverted
      repeats. telO is separated from these repeats by 3 bp on each side. The telRL
      sequence is sufficient for TelN-mediated processing. The ends of the DNA
      molecules generated in vitro have the same configuration as do those observed in
      vivo. TelN exerts its activity as cleaving-joining enzyme in a concerted action.

PMID- 10884404
TI  - Regulation of protein function by native metastability.
AB  - In common globular proteins, the native form is in its most stable state. In
      contrast, each native form exists in a metastable state in inhibitory serpins
      (serine protease inhibitors) and some viral membrane fusion proteins.
      Metastability in these proteins is critical to their biological functions.
      Mutational analyses and structural examination have previously revealed unusual
      interactions, such as side-chain overpacking, buried polar groups, and cavities
      as the structural basis of the native metastability. However, the mechanism by
      which these structural defects regulate protein functions has not been
      elucidated. We report here characterization of cavity-filling mutations of
      alpha(1)-antitrypsin, a prototype serpin. Conformational stability of the
      molecule increased linearly with the van der Waals volume of the side chains.
      Increasing conformational stability is correlated with decreasing inhibitory
      activity. Moreover, the activity loss appears to correlate with the decrease in
      the rate of the conformational switch during complex formation with a target
      protease. These results strongly suggest that the native metastability of
      proteins is indeed a structural design that regulates protein functions.

PMID- 10884405
TI  - Crystal structure of human stem cell factor: implication for stem cell factor
      receptor dimerization and activation.
AB  - Stem cell factor (SCF) plays important roles in hematopoiesis and the survival,
      proliferation, and differentiation of mast cells, melanocytes, and germ cells.
      SCF mediates its biological effects by binding to and activating a receptor
      tyrosine kinase designated c-kit or SCF receptor. In this report we describe the
      2.3-A crystal structure of the functional core of recombinant human SCF. SCF is a
      noncovalent homodimer composed of two slightly wedged protomers. Each SCF
      protomer exhibits an antiparallel four-helix bundle fold. Dimerization is
      mediated by extensive polar and nonpolar interactions between the two protomers
      with a large buried surface area. Finally, we have identified a hydrophobic
      crevice and a charged region at the tail of each protomer that functions as a
      potential receptor-binding site. On the basis of these observations, a model for
      SCF small middle dotc-kit complex formation and dimerization is proposed.

PMID- 10884406
TI  - BRG-1 is required for RB-mediated cell cycle arrest.
AB  - The antiproliferative action of the retinoblastoma tumor suppressor protein, RB,
      is disrupted in the majority of human cancers. Disruption of RB activity occurs
      through several disparate mechanisms, including viral oncoprotein binding,
      deregulated RB phosphorylation, and mutation of the RB gene. Here we report
      disruption of RB-signaling in tumor cells through loss of a critical cooperating
      factor. We have previously reported that C33A cells fail to undergo cell cycle
      inhibition in the presence of constitutively active RB (PSM-RB). To determine how
      C33A cells evade RB-mediated arrest, cell fusion experiments were performed with
      RB-sensitive cells. The resulting fusions were arrested by PSM-RB, indicating
      that C33A cells lack a factor required for RB-mediated cell cycle inhibition.
      C33A cells are deficient in BRG-1, a SWI/SNF family member known to stimulate RB
      activity. Consistent with BRG-1 deficiency underlying resistance to RB-mediated
      arrest, we identified two other BRG-1-deficient cell lines (SW13 and PANC-1) and
      demonstrate that these tumor lines are also resistant to cell cycle inhibition by
      PSM-RB and p16ink4a, which activates endogenous RB. In cell lines lacking BRG-1,
      we noted a profound defect in RB-mediated repression of the cyclin A promoter.
      This deficiency in RB-mediated transcriptional repression and cell cycle
      inhibition was rescued through ectopic coexpression of BRG-1. We also demonstrate
      that 3T3-derived cells, which inducibly express a dominant-negative BRG-1, arrest
      by PSM-RB and p16ink4a in the absence of dominant-negative BRG-1 expression;
      however, cell cycle arrest was abrogated on induction of dominant-negative BRG-1.
      These findings demonstrate that BRG-1 loss renders cells resistant to RB-mediated
      cell cycle progression, and that disruption of RB signaling through loss of
      cooperating factors occurs in cancer cells.

PMID- 10884407
TI  - The N-terminal domains of histones H3 and H4 are not necessary for chromatin
      assembly factor-1- mediated nucleosome assembly onto replicated DNA in vitro.
AB  - An in vitro reconstitution system for the analysis of replication-coupled
      nucleosome assembly is described. In this "two-step system," nucleosome assembly
      is performed in a separate reaction from DNA replication, wherein purified newly
      replicated DNA remains noncovalently marked for subsequent chromatin assembly
      factor-1 (CAF-1)-dependent nucleosome assembly. Because the nucleosome assembly
      is performed separately from the DNA replication step, this system is more
      versatile and biochemically tractable when compared with nucleosome assembly
      during simian virus 40 (SV40) DNA replication. The N-terminal domains of histones
      H3 and H4 play an important but redundant function in nucleosome assembly in the
      budding yeast, Saccharomyces cerevisiae. It had been proposed that at least one
      tail of histone H3 or H4 is required for replication-coupled nucleosome assembly.
      However, we demonstrate that the N-terminal domains of both histone H3 and H4 are
      dispensable for CAF-1-mediated formation of nucleosome cores onto newly
      replicated DNA in vitro. CAF-1 and each of its individual subunits stably bound
      to recombinant (H3.H4)(2) tetramers lacking the N-terminal domains of both H3 and
      H4. Therefore, the N-terminal tails of histone H3 and H4 that contain the
      specific acetylation sites are not necessary for CAF-1-dependent nucleosome
      assembly onto replicated DNA. We suggest that the histone acetylation may be
      required for a CAF-1 independent pathway or function after deposition, by marking
      of newly replicated chromatin.

PMID- 10884408
TI  - tmRNAs that encode proteolysis-inducing tags are found in all known bacterial
      genomes: A two-piece tmRNA functions in Caulobacter.
AB  - A general mechanism in bacteria to rescue stalled ribosomes and to clear the cell
      of incomplete polypeptides involves an RNA species, tmRNA (SsrA), which functions
      as both a tRNA and an mRNA. This RNA encodes a peptide tag that is incorporated
      at the end of the aberrant polypeptide and targets it for proteolysis. We have
      identified a circularly permuted version of the tmRNA gene in alpha
      proteobacteria as well as in a lineage of cyanobacteria. The genes in these two
      groups seem to have arisen from two independent permutation events. As a result
      of the altered genetic structure, these tmRNAs are composed of two distinct RNA
      molecules. The mature two-piece tmRNAs are predicted to have a tRNA-like domain
      and an mRNA-like domain similar to those of standard one-piece tmRNAs, with a
      break located in the loop containing the tag reading frame. A related sequence
      was found in the mitochondrial genome of Reclinomonas americana, but only the
      tRNA-like portion is retained. Although several sequence and structural motifs
      that are conserved among one-piece tmRNAs have been lost, the alpha
      proteobacterium Caulobacter crescentus produces a functional two-piece tmRNA.

PMID- 10884409
TI  - Escherichia coli CspA-family RNA chaperones are transcription antiterminators.
AB  - CspA, the major cold-shock protein of Escherichia coli, is an RNA chaperone,
      which is thought to facilitate translation at low temperature by destabilizing
      mRNA structures. Here we demonstrate that CspA, as well as homologous RNA
      chaperones CspE and CspC, are transcription antiterminators. In vitro, the
      addition of physiological concentrations of recombinant CspA, CspE, or CspC
      decreased transcription termination at several intrinsic terminators and also
      decreased transcription pausing. In vivo, overexpression of cloned CspC and CspE
      at 37 degrees C was sufficient to induce transcription of the metY-rpsO operon
      genes nusA, infB, rbfA, and pnp located downstream of multiple transcription
      terminators. Similar induction of downstream metY-rpsO operon genes was observed
      at cold shock, a condition to which the cell responds by massive overproduction
      of CspA. The products of nusA, infB, rbfA, and pnp-NusA, IF2, RbfA, and PNP-are
      known to be induced at cold shock. We propose that the cold-shock induction of
      nusA, infB, rbfA, and pnp occurs through transcription antitermination, which is
      mediated by CspA and other cold shock-induced Csp proteins.

PMID- 10884410
TI  - Nuclear accumulation of cyclin E/Cdk2 triggers a concentration-dependent switch
      for the destruction of p27Xic1.
AB  - The action of cyclin-dependent kinases (CDKs) is regulated by phosphorylation,
      cyclin levels, the abundance of CDK inhibitors, and, as recently has been shown
      for cyclin B/cdc2, their localization. It is unclear how localization regulates
      the action of cyclin E/Cdk2 and its inhibitors. Here, we show that the closest
      known Xenopus laevis homolog of mammalian Cdk2 inhibitors p27(Kip1) and
      p21(CIP1), Xic1, is concentrated, ubiquitinated, and destroyed in the nucleus.
      Furthermore, Xic1 destruction requires nuclear import, but not nuclear export,
      and requires the formation of a transport-competent nuclear envelope, but not
      interactions between the lamina and chromatin. We show that (i) cyclin E/Cdk2 and
      Xic1 are transported into the nucleus as a complex and that Xic1 destruction
      requires the activity of cyclin E, (ii) that phosphorylation of Xic1 by cyclin
      E/Cdk2 bypasses the requirement for nuclear formation, and (iii) that the
      phosphorylation of Xic1 by cyclin E/Cdk2 is concentration dependent and likely
      realized through second-order interactions between stable cyclin E/Cdk2/Xic1
      ternary complexes. Based on these results we propose a model wherein nuclear
      accumulation of the cyclin E/Cdk2/Xic1 complex triggers a concentration-dependent
      switch that promotes the phosphorylation of Xic1 and, consequently, its
      ubiquitination and destruction, thus allowing subsequent activation of cyclin
      E/Cdk2.

PMID- 10884411
TI  - A DNA enzyme with N-glycosylase activity.
AB  - In vitro evolution was used to develop a DNA enzyme that catalyzes the site
      specific depurination of DNA with a catalytic rate enhancement of about 10(6)
      fold. The reaction involves hydrolysis of the N-glycosidic bond of a particular
      deoxyguanosine residue, leading to DNA strand scission at the apurinic site. The
      DNA enzyme contains 93 nucleotides and is structurally complex. It has an
      absolute requirement for a divalent metal cation and exhibits optimal activity at
      about pH 5. The mechanism of the reaction was confirmed by analysis of the
      cleavage products by using HPLC and mass spectrometry. The isolation and
      characterization of an N-glycosylase DNA enzyme demonstrates that single-stranded
      DNA, like RNA and proteins, can form a complex tertiary structure and catalyze a
      difficult biochemical transformation. This DNA enzyme provides a new approach for
      the site-specific cleavage of DNA molecules.

PMID- 10884412
TI  - Phosphatase activity of histidine kinase EnvZ without kinase catalytic domain.
AB  - Most histidine kinases are bifunctional enzymes having both kinase and
      phosphatase activities. The cytoplasmic kinase domain of EnvZ, a transmembrane
      histidine kinase functioning as an osmosensor in Escherichia coli, consists of
      two distinct functional subdomains: domain A [EnvZc(223-289)] and domain B
      [EnvZc(290-450)]. NMR studies demonstrated that domain A consists of a four-helix
      bundle serving as a dimerization and phosphotransfer domain, and domain B
      functions as the ATP-binding and catalytic domain. Here we demonstrate that
      domain A by itself has the phosphatase activity both in vitro and in vivo. This
      phosphatase activity is Mg(2+) dependent but is not activated by ADP, ATP, or
      adenosine 5'-[beta, gamma-imido]triphosphate (AMPPNP), each of which may serve as
      a cofactor for the EnvZ phosphatase activity. Domain B showed a small but
      distinct effect on the domain A phosphatase activity only in the presence of ADP
      or AMPPNP. However, when domain B was covalently linked to domain A, dramatic
      cofactor-dependent enhancement of the phosphatase activity was observed.
      Extending domain A for another 75 residues at the C terminus or 44 residues at
      the N terminus did not enhance its phosphatase activity. Substitution mutations
      at His-243, the autophosphorylation site, demonstrate that the His residue plays
      an essential role in the phosphatase activity. The so-called X-region mutant
      L288P that is known to specifically abolish the phosphatase activity in EnvZ had
      no effect on the domain A phosphatase function. We propose that the EnvZ
      phosphatase activity is regulated by relative positioning of domains A and B,
      which is controlled by external signals. We also propose that the His-243 residue
      participates in both kinase and phosphatase reactions.

PMID- 10884413
TI  - On the kinetics of distamycin binding to its target sites on duplex DNA.
AB  - Distamycin A is a well known polyamide antibiotic that can bind in the minor
      groove of duplex DNA primarily at AT-rich sequences both as a monomer or as a
      side-by-side antiparallel dimer. The association phase of the distamycin binding
      reaction has not been studied in either of its binding modes, because of the lack
      of an adequate UV or CD signal at the low concentrations needed to monitor the
      fast bimolecular reaction. We report a significant increase in fluorescence
      amplitude, accompanied by a small red shift, on binding distamycin to its
      specific target sites. This signal can be used to monitor drug binding in steady
      state and time-resolved processes. Distamycin shows extremely fast association
      with the 1:1 binding site, with a bimolecular rate of 7 x 10(7) M(-1) small
      middle dots(-1) and also fairly rapid dissociation ( approximately 3 s(-1)). When
      DNA is in excess, there is a slow component in the association reaction whose
      rate decreases strongly with increasing DNA concentration. Binding of the drug to
      the 2:1 site occurs in two distinct steps: fast, sequential binding of each drug
      molecule to the DNA with a bimolecular rate comparable to that at the 1:1 site,
      followed by a slow ( approximately 4 s(-1)) equilibration to the final
      population. Dissociation from the 2:1 site is approximately 40-fold slower than
      from the 1:1 site. This study provides the groundwork for analysis of the binding
      kinetics of longer polyamides and covalently linked polyamides that have recently
      been shown to inhibit transcription in vivo.

PMID- 10884414
TI  - Two mechanisms for termination of individual Ca2+ sparks in skeletal muscle.
AB  - Ca(2+) sparks are brief, localized elevations of myoplasmic [Ca(2+)] caused by
      release of increments of Ca(2+) via sarcoplasmic reticulum Ca(2+) release
      channels in muscle. The properties of individual sparks provide information
      regarding the opening of sarcoplasmic reticulum Ca(2+) channels within
      functioning cells. Here we use high-speed confocal microscopy to show that
      individual Ca(2+) sparks activated by membrane depolarization in single frog
      skeletal muscle fibers can be terminated prematurely by repolarization. Thus,
      either voltage sensor deactivation on repolarization or release channel
      inactivation during continued depolarization can terminate the Ca(2+) release
      channel activity underlying voltage-activated Ca(2+) sparks in skeletal muscle.

PMID- 10884415
TI  - A distinct nuclear localization signal in the N terminus of Smad 3 determines its
      ligand-induced nuclear translocation.
AB  - Smad proteins are intracellular mediators of transforming growth factor beta (TGF
      beta) and related cytokines and undergo ligand-induced nuclear translocation.
      Here we describe the identification of a nuclear localization signal (NLS) in the
      N-terminal region of Smad 3, the major Smad protein involved in TGF-beta
      signaling. An NLS-like basic motif (Lys(40)-Lys-Leu-Lys-Lys(44)), conserved among
      all pathway-specific Smad proteins, not only is responsible for constitutive
      nuclear localization of the isolated Smad 3 MH1 domain but also is crucial for
      Smad 3 nuclear import in response to ligand. Mutations in this motif completely
      abolished TGF-beta-induced nuclear translocation but had no impact on ligand
      induced phosphorylation of Smad 3, complex formation with Smad 4, or specific
      binding to DNA. Hence Smad 3 proteins with NLS mutations are dominant-negative
      inhibitors of TGF-beta-induced transcriptional activation. Smad 4, which cannot
      translocate into the nucleus in the absence of Smad 3 or another pathway-specific
      Smad, contains a Glu in place of the last Lys in this motif. Smad 3 harboring the
      same mutation (K44E) does not undergo ligand-induced nuclear import. Conversely,
      the isolated Smad 4 MH1 domain does not accumulate in the nucleus but becomes
      nuclear enriched when Glu(49) is replaced with Lys. We propose that this highly
      conserved five-residue NLS motif determines ligand-induced nuclear translocation
      of all pathway-specific Smads.

PMID- 10884416
TI  - Modeling the fission yeast cell cycle: quantized cycle times in wee1- cdc25Delta
      mutant cells.
AB  - A detailed mathematical model for the fission yeast mitotic cycle is developed
      based on positive and negative feedback loops by which Cdc13/Cdc2 kinase
      activates and inactivates itself. Positive feedbacks are created by Cdc13/Cdc2
      dependent phosphorylation of specific substrates: inactivating its negative
      regulators (Rum1, Ste9 and Wee1/Mik1) and activating its positive regulator
      (Cdc25). A slow negative feedback loop is turned on during mitosis by activation
      of Slp1/anaphase-promoting complex (APC), which indirectly re-activates the
      negative regulators, leading to a drop in Cdc13/Cdc2 activity and exit from
      mitosis. The model explains how fission yeast cells can exit mitosis in the
      absence of Ste9 (Cdc13 degradation) and Rum1 (an inhibitor of Cdc13/Cdc2). We
      also show that, if the positive feedback loops accelerating the G(2)/M transition
      (through Wee1 and Cdc25) are weak, then cells can reset back to G(2) from early
      stages of mitosis by premature activation of the negative feedback loop. This
      resetting can happen more than once, resulting in a quantized distribution of
      cycle times, as observed experimentally in wee1(-) cdc25Delta mutant cells. Our
      quantitative description of these quantized cycles demonstrates the utility of
      mathematical modeling, because these cycles cannot be understood by intuitive
      arguments alone.

PMID- 10884417
TI  - Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific
      death program that is independent of caspases and bypasses Bcl-2.
AB  - Heat shock protein 70 is an antiapoptotic chaperone protein highly expressed in
      human breast tumors and tumor cell lines. Here, we demonstrate that the mere
      inhibition of its synthesis by adenoviral transfer or classical transfection of
      antisense Hsp70 cDNA (asHsp70) results in massive death of human breast cancer
      cells (MDA-MB-468, MCF-7, BT-549, and SK-BR-3), whereas the survival of
      nontumorigenic breast epithelial cells (HBL-100) or fibroblasts (WI-38) is not
      affected. Despite the apoptotic morphology as judged by electron microscopy, the
      asHsp70-induced death was independent of known caspases and the p53 tumor
      suppressor protein. Furthermore, Bcl-2 and Bcl-X(L), which protect tumor cells
      from most forms of apoptosis, failed to rescue breast cancer cells from asHsp70
      induced death. These results show that tumorigenic breast cancer cells depend on
      the constitutive high expression of Hsp70 to suppress a transformation-associated
      death program. Neutralization of Hsp70 may open new possibilities for treatment
      of cancers that have acquired resistance to therapies activating the classical
      apoptosis pathway.

PMID- 10884418
TI  - SEL-8, a nuclear protein required for LIN-12 and GLP-1 signaling in
      Caenorhabditis elegans.
AB  - LIN-12 and GLP-1 are members of the LIN-12/Notch family of receptors that mediate
      cell-cell interactions during development. The sel-8 gene had been identified
      previously in a screen for suppressors of a mutation that constitutively
      activates LIN-12. Here, we report that sel-8 is essential for lin-12- and glp-1
      mediated signaling, and that SEL-8 is a glutamine-rich nuclear protein. We
      postulate that SEL-8 serves as a transcriptional coactivator or as an assembly
      factor for transcription complexes that contain the LIN-12 or GLP-1 intracellular
      domains.

PMID- 10884419
TI  - Endothelin 3 induces the reversion of melanocytes to glia through a neural crest
      derived glial-melanocytic progenitor.
AB  - Functional signaling of endothelin 3 (ET3) and its receptor B (ETRB) has been
      shown to be required for the development of neural crest (NC)-derived pigment
      cells in mouse, but the precise role of ET3 is not completely understood. Using
      the avian embryo as a model, we previously reported that ET3 promotes the
      survival and proliferation of unipotent melanocyte and bipotent glia-melanocyte
      precursors in trunk NC cultures. Here we investigated whether, at later stages,
      embryonic pigment cells respond to ET3. Such a possibility is supported by the
      previous finding that, in vivo, avian melanocytes express endothelin receptor B2
      (ETRB2) during migration and after their differentiation in the skin. We found
      that in vitro ET3 exerts a dose-dependent stimulation of proliferation and
      melanogenesis in NC cells that had homed to the epidermis of embryonic quail
      dorsal skin. Moreover, in clonal cultures of skin-derived pigment cells, ET3
      induces rapid cell divisions of clonogenic melanocytes that generate a mixed
      progeny of melanocytes and cells devoid of pigment granules and expressing glial
      markers in more than 40% of the colonies. It can therefore be concluded that ET3
      is strongly mitogenic to embryonic pigment cells and able to alter their
      differentiation program, leading them to recapitulate the glial-melanocyte
      bipotentiality of their NC ancestors.

PMID- 10884420
TI  - JNK and decapentaplegic signaling control adhesiveness and cytoskeleton dynamics
      during thorax closure in Drosophila.
AB  - One of the fundamental events in metamorphosis in insects is the replacement of
      larval tissues by imaginal tissues. Shortly after pupariation the imaginal discs
      evaginate to assume their positions at the surface of the prepupal animal. This
      is a very precise process that is only beginning to be understood. In Drosophila,
      during embryonic dorsal closure, the epithelial cells push the amnioserosa cells,
      which contract and eventually invaginate in the body cavity. In contrast, we find
      that during pupariation the imaginal cells crawl over the passive larval tissue
      following a very accurate temporal and spatial pattern. Spreading is driven by
      filopodia and actin bridges that, protruding from the leading edge, mediate the
      stretching of the imaginal epithelia. Although interfering with JNK (Jun N
      terminal kinase) and dpp (decapentaplegic) produces similar phenotypic effects
      suppressing closure, their effects at the cellular level are different. The loss
      of JNK activity alters the adhesion properties of larval cells and leads to the
      detachment of the imaginal and larval tissues. The absence of dpp signaling
      affects the actin cytoskeleton, blocks the emission of filopodia, and promotes
      the collapse of the leading edge of the imaginal tissues. Interestingly, these
      effects are very similar to those observed after interfering with JNK and dpp
      signaling during embryonic dorsal closure.

PMID- 10884421
TI  - Establishing a grassland signature in veins: 18O in the leaf water of C3 and C4
      grasses.
AB  - We show that 18O evaporative enrichment of bulk leaf water in grass species can
      be significantly more enriched than predicted by the Craig-Gordon model, with C4
      grasses considerably more enriched than C3 grasses. Our results suggest that the
      unanticipated 18O leaf water enrichment of grasses is attributable to the
      progressive evaporative enrichment along parallel veins (a function of both leaf
      length and interveinal distance), a pattern that does not occur in Dicotyledonous
      species. We propose that the differential 18O enrichment of grasses will result
      in distinct C18O16O biospheric signals from grassland and forest ecosystems,
      allowing for further partitioning of terrestrial carbon fluxes.

PMID- 10884422
TI  - Miocene ungulates and terrestrial primary productivity: where have all the
      browsers gone?
AB  - Progressive changes are observed in both the composition of mammal faunas and
      vegetation during the Miocene epoch [24-5 mega-annum (Ma)]. These changes are
      usually interpreted as a response to climatic changes. In the traditional view,
      forests or woodlands gradually gave way to more open habitats, with grazing
      (grass-eating) ungulate (hoofed) mammal species replacing the browsing (leafy
      vegetation-eating) species as grasslands expanded. However, data from fossil
      assemblages in the Great Plains region of North America show that this faunal
      change was not a one-for-one replacement of browsers by grazers, as usually
      thought. Typical late early Miocene (17 Ma) fossil communities included
      extraordinarily high numbers of browsing ungulate species, comprising a fauna
      that cannot be directly analogized with any present-day community. Both maximum
      species richness of all ungulates and the proportion of browsers declined
      steadily in ungulate communities through the middle Miocene, to levels comparable
      to those of the present by the late Miocene. The resulting dramatic, cumulative
      loss of browsing species constitutes one of the strongest faunal signals of the
      late Tertiary (but was not a single "event"). We suggest that the early Miocene
      browser-rich communities may reflect higher levels of primary productivity in
      Miocene vegetation, compared with equivalent present-day vegetation types. The
      observed decline in species richness may represent a gradual decline in primary
      productivity, which would be consistent with one current hypothesis of a mid
      Miocene decrease in atmospheric CO2 concentrations from higher mid-Cenozoic
      values.

PMID- 10884423
TI  - Natural selection mapping of the warfarin-resistance gene.
AB  - In theory, genes under natural selection can be revealed by unique patterns of
      linkage disequilibrium (LD) and polymorphism at physically linked loci. However,
      given the effects of recombination and mutation, the physical extent and
      persistence of LD patterns in natural populations is uncertain. To assess the LD
      signature of selection, we survey variation in 26 microsatellite loci spanning an
      approximately 32-cM region that includes the warfarin-resistance gene (Rw) in
      five wild rat populations having resistance levels between 0 and 95%. We find a
      high frequency of heterozygote deficiency at microsatellite loci in resistant
      populations, and a negative association between gene diversity (H) and
      resistance. Contrary to previous studies, these data suggest that directional
      rather than overdominant selection may predominate during periods of intense
      anticoagulant treatment. In highly resistant populations, extensive LD was
      observed over a chromosome segment spanning approximately 14% of rat chromosome
      1. In contrast, LD in a moderately resistant population was more localized and,
      in conjunction with likelihood ratios, allowed assignment of Rw to a 2. 2-cM
      interval. Within this genomic window, a diagnostic marker, D1Rat219, assigned 91%
      of rats to the correct resistance category. These results further demonstrate
      that "natural selection mapping" in field populations can detect and map major
      fitness-related genes, and question overdominance as the predominant mode of
      selection in anticoagulant-resistant rat populations.

PMID- 10884425
TI  - Model selection for quantitative trait locus analysis in polyploids.
AB  - Over the years, substantial gains have been made in locating regions of
      agricultural genomes associated with characteristics, diseases, and agroeconomic
      traits. These gains have relied heavily on the ability to statistically estimate
      the association between DNA markers and regions of a genome (quantitative trait
      loci or QTL) related to a particular trait. The majority of these advances have
      focused on diploid species, even though many important agricultural crops are, in
      fact, polyploid. The purpose of our work is to initiate an algorithmic approach
      for model selection and QTL detection in polyploid species. This approach
      involves the construction of all possible chromosomal configurations (models)
      that may result in a gamete, model reduction based on estimation of marker dosage
      from progeny data, and lastly model selection. While simplified for initial
      explanation, our approach has demonstrated itself to be extendible to many
      breeding schemes and less restricted settings.

PMID- 10884424
TI  - Dysfunction of human Rad18 results in defective postreplication repair and
      hypersensitivity to multiple mutagens.
AB  - Postreplication repair functions in gap-filling of a daughter strand on
      replication of damaged DNA. The yeast Saccharomyces cerevisiae Rad18 protein
      plays a pivotal role in the process together with the Rad6 protein. Here, we have
      cloned a human homologue of RAD18, hRAD18. It maps on chromosome 3p24-25, where
      deletions are often found in lung, breast, ovary, and testis cancers. In vivo,
      hRad18 protein binds to hHR6 protein through a conserved ring-finger motif.
      Stable transformants with hRad18 mutated in this motif become sensitive to UV,
      methyl methanesulfonate, and mitomycin C, and are defective in the replication of
      UV-damaged DNA. Thus, hRAD18 is a functional homologue of RAD18.

PMID- 10884426
TI  - Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast.
AB  - The Zap1p transcription factor senses cellular zinc status and increases
      expression of its target genes in response to zinc deficiency. Previously known
      Zap1p-regulated genes encode the Zrt1p, Zrt2p, and Zrt3p zinc transporter genes
      and Zap1p itself. To allow the characterization of additional genes in yeast
      important for zinc homeostasis, a systematic study of gene expression on the
      genome-wide scale was used to identify other Zap1p target genes. Using a
      combination of DNA microarrays and a computer-assisted analysis of shared motifs
      in the promoters of similarly regulated genes, we identified 46 genes that are
      potentially regulated by Zap1p. Zap1p-regulated expression of seven of these
      newly identified target genes was confirmed independently by using lacZ reporter
      fusions, suggesting that many of the remaining candidate genes are also Zap1p
      targets. Our studies demonstrate the efficacy of this combined approach to define
      the regulon of a specific eukaryotic transcription factor.

PMID- 10884427
TI  - Direct selection of a human antibody fragment directed against the tumor T-cell
      epitope HLA-A1-MAGE-A1 from a nonimmunized phage-Fab library.
AB  - Antitumor antibodies with the same specificity as cytotoxic T lymphocytes that
      recognize antigenic peptides encoded by tumor-associated genes and presented by
      MHC class I molecules would be valuable tools to analyze the antigenicity or
      target tumor cells in vivo. To obtain a human antibody directed against a peptide
      encoded by gene melanoma-associated antigen (MAGE)-A1 and presented by HLA-A1
      molecules, we selected a large phage Fab antibody repertoire on a recombinant
      version of the complex HLA-A1-MAGE-A1 produced by in vitro refolding. One of the
      selected phage antibodies shows binding to HLA-A1 complexed with the MAGE-A1
      peptide, but does not show binding to HLA-A1 complexed with a peptide encoded by
      gene MAGE-A3 and differing from the MAGE-A1 peptide by only three residues.
      Phages carrying this recombinant antibody bind to HLA-A1(+) cells only after in
      vitro loading with MAGE-A1 peptide. These results indicate that nonimmunized
      phage Fab libraries are a source of antibodies with a T cell antigen receptor
      like specificity. The human anti-HLA-A1-MAGE-A1 antibody described here may prove
      very useful for monitoring the cell surface expression of these complexes, and
      eventually, as a targeting reagent for the specific immunotherapy of HLA-A1
      patients bearing a MAGE-A1-positive tumor.

PMID- 10884429
TI  - In vitro cultivation of human islets from expanded ductal tissue.
AB  - A major obstacle to successful islet transplantation for both type 1 and 2
      diabetes is an inadequate supply of insulin-producing tissue. This need for
      transplantable human islets has stimulated efforts to expand existing pancreatic
      islets and/or grow new ones. To test the hypothesis that human adult duct tissue
      could be expanded and differentiated in vitro to form islet cells, digested
      pancreatic tissue that is normally discarded from eight human islet isolations
      was cultured under conditions that allowed expansion of the ductal cells as a
      monolayer whereupon the cells were overlaid with a thin layer of Matrigel. With
      this manipulation, the monolayer of epithelial cells formed three-dimensional
      structures of ductal cysts from which 50-to 150- micrometer diameter islet-like
      clusters of pancreatic endocrine cells budded. Over 3-4 weeks culture the insulin
      content per flask increased 10- to 15-fold as the DNA content increased up to 7
      fold. The cultivated human islet buds were shown by immunofluorescence to consist
      of cytokeratin 19-positive duct cells and hormone-positive islet cells. Double
      staining of insulin and non-beta cell hormones in occasional cells indicated
      immature cells still in the process of differentiation. Insulin secretion studies
      were done over 24 h in culture. Compared with their basal secretion at 5 mM
      glucose, cysts/cultivated human islet buds exposed to stimulatory 20 mM glucose
      had a 2.3-fold increase in secreted insulin. Thus, duct tissue from human
      pancreas can be expanded in culture and then be directed to differentiate into
      glucose responsive islet tissue in vitro. This approach may provide a potential
      new source of pancreatic islet cells for transplantation.

PMID- 10884428
TI  - Complete genomic sequence of the human ABCA1 gene: analysis of the human and
      mouse ATP-binding cassette A promoter.
AB  - The ABCA1 gene, a member of the ATP-binding cassette A (ABCA1) transporter
      superfamily, encodes a membrane protein that facilitates the cellular efflux of
      cholesterol and phospholipids. Mutations in ABCA1 lead to familial high density
      lipoprotein deficiency and Tangier disease. We report the complete human ABCA1
      gene sequence, including 1,453 bp of the promoter, 146,581 bp of introns and
      exons, and 1 kb of the 3' flanking region. The ABCA1 gene spans 149 kb and
      comprises 50 exons. Sixty-two repetitive Alu sequences were identified in introns
      1-49. The transcription start site is 315 bp upstream of a newly identified
      initiation methionine codon and encodes an ORF of 6,783 bp. Thus, the ABCA1
      protein is comprised of 2,261 aa. Analysis of the 1,453 bp 5' upstream of the
      transcriptional start site reveals multiple binding sites for transcription
      factors with roles in lipid metabolism. Comparative analysis of the mouse and
      human ABCA1 promoter sequences identified specific regulatory elements, which are
      evolutionarily conserved. The human ABCA1 promoter fragment -200 to -80 bp that
      contains binding motifs for SP1, SP3, E-box, and AP1 modulates cellular
      cholesterol and cAMP regulation of ABCA1 gene expression. These combined findings
      provide insights into ABCA1-mediated regulation of cellular cholesterol
      metabolism and will facilitate the identification of new pharmacologic agents for
      the treatment of atherosclerosis in humans.

PMID- 10884430
TI  - Genetically modified anthrax lethal toxin safely delivers whole HIV protein
      antigens into the cytosol to induce T cell immunity.
AB  - Bacillus anthrax lethal toxin can be engineered to deliver foreign proteins to
      the cytosol for antigen presentation to CD8 T cells. Vaccination with modified
      toxins carrying 8-9 amino acid peptide epitopes induces protective immunity in
      mice. To evaluate whether large protein antigens can be used with this system,
      recombinant constructs encoding several HIV antigens up to 500 amino acids were
      produced. These candidate HIV vaccines are safe in animals and induce CD8 T cells
      in mice. Constructs encoding gag p24 and nef stimulate gag-specific CD4
      proliferation and a secondary cytotoxic T lymphocyte response in HIV-infected
      donor peripheral blood mononuclear cells in vitro. These results lay the
      foundation for future clinical vaccine studies.

PMID- 10884432
TI  - Experience-dependent plasticity in the auditory cortex and the inferior
      colliculus of bats: role of the corticofugal system.
AB  - In the big brown bat, Eptesicus fuscus, the response properties of neurons and
      the cochleotopic (frequency) maps in the auditory cortex (AC) and inferior
      colliculus can be changed by auditory conditioning, weak focal electric
      stimulation of the AC, or repetitive delivery of weak, short tone bursts. The
      corticofugal system plays an important role in information processing and
      plasticity in the auditory system. Our present findings are as follows. In the
      AC, best frequency (BF) shifts, i.e., reorganization of a frequency map, slowly
      develop and reach a plateau approximately 180 min after conditioning with tone
      bursts and electric-leg stimulation. The plateau lasts more than 26 h. In the
      inferior colliculus, on the other hand, BF shifts rapidly develop and become the
      largest at the end of a 30-min-long conditioning session. The shifted BFs return
      (i. e., recover) to normal in approximately 180 min. The collicular BF shifts are
      not a consequence of the cortical BF shifts. Instead, they lead the cortical BF
      shifts. The collicular BF shifts evoked by conditioning are very similar to the
      collicular and cortical BF shifts evoked by cortical electrical stimulation.
      Therefore, our working hypothesis is that, during conditioning, the corticofugal
      system evokes subcortical BF shifts, which in turn boost cortical BF shifts. The
      cortical BF shifts otherwise would be very small. However, whether the cortical
      BF shifts are consequently boosted depends on nonauditory systems, including
      nonauditory sensory cortices, amygdala, basal forebrain, etc., which determine
      the behavioral relevance of acoustic stimuli.

PMID- 10884431
TI  - Tumor necrosis factor alpha mediates apoptosis of brown adipocytes and defective
      brown adipocyte function in obesity.
AB  - Severe quantitative and qualitative brown adipocyte defects are common in
      obesity. To investigate whether aberrant expression of tumor necrosis factor
      alpha (TNF-alpha) in obesity is involved in functional brown fat atrophy, we have
      studied genetically obese (ob/ob) mice with targeted null mutations in the genes
      encoding the two TNF receptors. The absence of both TNF receptors or p55 receptor
      alone resulted in a significant reduction in brown adipocyte apoptosis and an
      increase in beta(3)-adrenoreceptor and uncoupling protein-1 expression in obese
      mice. Increased numbers of multilocular functionally active brown adipocytes, and
      improved thermoregulation was also observed in obese animals lacking TNF-alpha
      function. These results indicate that TNF-alpha plays an important role in
      multiple aspects of brown adipose tissue biology and mediates the abnormalities
      that occur at this site in obesity.

PMID- 10884433
TI  - Nonreceptor tyrosine protein kinase pp60c-src in spatial learning: synapse
      specific changes in its gene expression, tyrosine phosphorylation, and protein
      protein interactions.
AB  - c-src is a nonreceptor tyrosine protein kinase that is highly concentrated in
      synaptic regions, including synaptic vesicles and growth cones. Here, we report
      that the mRNA signal of pp60c-src is widely distributed in the rat brain with
      particularly high concentrations in the hippocampus. After spatial maze learning,
      up-regulation of c-src mRNA was observed in the CA3 region of the hippocampus,
      which was accompanied by increases in pp60c-src protein in hippocampal
      synaptosomal preparations. Training also triggered an increase in c-src protein
      tyrosine kinase activity that was correlated with its tyrosine dephosphorylation
      in the synaptic membrane fraction. After training, pp60c-src from hippocampus
      showed enhanced interactions with synaptic proteins such as synapsin I,
      synaptophysin, and the type 2 N-methyl-d-aspartate receptor, as well as the
      cytoskeletal protein actin. The association of pp60c-src with insulin receptor in
      the synaptic membrane fraction, however, was temporally decreased after training.
      Furthermore, in vitro results showed that Ca(2+) and protein kinase C might be
      involved in the regulation of protein-protein interactions of pp60c-src. These
      results suggest, therefore, that pp60c-src participates in the regulation of
      hippocampal synaptic activity during learning and memory.

PMID- 10884434
TI  - Increased baseline occupancy of D2 receptors by dopamine in schizophrenia.
AB  - The classical dopamine hypothesis of schizophrenia postulates a hyperactivity of
      dopaminergic transmission at the D(2) receptor. We measured in vivo occupancy of
      striatal D(2) receptors by dopamine in 18 untreated patients with schizophrenia
      and 18 matched controls, by comparing D(2) receptor availability before and
      during pharmacologically induced acute dopamine depletion. Acute depletion of
      intrasynaptic dopamine resulted in a larger increase in D(2) receptor
      availability in patients with schizophrenia (19% +/- 11%) compared with control
      subjects (9% +/- 7%, P = 0.003). The increased occupancy of D(2) receptors by
      dopamine occurred both in first-episode neuroleptic-naive patients and in
      previously treated chronic patients experiencing an episode of illness
      exacerbation. In addition, elevated synaptic dopamine was predictive of good
      treatment response of positive symptoms to antipsychotic drugs. This finding
      provides direct evidence of increased stimulation of D(2) receptors by dopamine
      in schizophrenia, consistent with increased phasic activity of dopaminergic
      neurons.

PMID- 10884435
TI  - Mushroom body defect, a gene involved in the control of neuroblast proliferation
      in Drosophila, encodes a coiled-coil protein.
AB  - Neurogenesis relies on the establishment of the proper number and precisely
      controlled proliferation of neuroblasts, the neuronal precursor cells. A role for
      the mushroom body defect (mud) gene in both of these aspects of neuroblast
      behavior, as well as possible roles in other aspects of fruit fly biology, is
      implied by phenotypes associated with mud mutations. We have localized mud by
      determining the sequence change in one point mutant, identifying a predicted ORF
      affected by the mutation, and showing that an appropriate segment of the genome
      rescues mud mutant phenotypes. An analysis of mud cDNAs and a survey of mud
      transcripts by Northern blotting indicate that the gene is subject to
      differential splicing and is expressed primarily during embryogenesis but also,
      at lower levels, during subsequent developmental stages in a sexually dimorphic
      manner. The gene is predicted to encode a polypeptide without obvious homologs
      but with two prominent structural features, a long coiled coil that constitutes
      the central core of the protein and a carboxyl-terminal transmembrane domain.

PMID- 10884436
TI  - Retrograde axonal transport of herpes simplex virus: evidence for a single
      mechanism and a role for tegument.
AB  - Herpes simplex virus type I (HSV) typically enters peripheral nerve terminals and
      then travels back along the nerve to reach the neuronal cell body, where it
      replicates or enters latency. To monitor axoplasmic transport of HSV, we used the
      giant axon of the squid, Loligo pealei, a well known system for the study of
      axoplasmic transport. To deliver HSV into the axoplasm, viral particles stripped
      of their envelopes by detergent were injected into the giant axon, thereby
      bypassing the infective process. Labeling the viral tegument protein, VP16, with
      green fluorescent protein allowed viral particles moving inside the axon to be
      imaged by confocal microscopy. Viral particles moved 2.2 +/- 0.26 micrometer/sec
      in the retrograde direction, a rate comparable to that of the transport of
      endogenous organelles and of virus in mammalian neurons in culture. Electron
      microscopy confirmed that 96% of motile (stripped) viral particles had lost their
      envelope but retained tegument, and Western blot analysis revealed that these
      particles had retained protein from capsid but not envelope. We conclude that (i)
      HSV recruits the squid retrograde transport machinery; (ii) viral tegument and
      capsid but not envelope are sufficient for this recruitment; and (iii) the giant
      axon of the squid provides a unique system to dissect the viral components
      required for transport and to identify the cellular transport mechanisms they
      recruit.

PMID- 10884437
TI  - Design of a potent and selective inhibitor of the intermediate-conductance Ca2+
      activated K+ channel, IKCa1: a potential immunosuppressant.
AB  - The antimycotic clotrimazole, a potent inhibitor of the intermediate-conductance
      calcium-activated K(+) channel, IKCa1, is in clinical trials for the treatment of
      sickle cell disease and diarrhea and is effective in ameliorating the symptoms of
      rheumatoid arthritis. However, inhibition of cytochrome P450 enzymes by
      clotrimazole limits its therapeutic value. We have used a rational design
      strategy to develop a clotrimazole analog that selectively inhibits IKCa1 without
      blocking cytochrome P450 enzymes. A screen of 83 triarylmethanes revealed the
      pharmacophore for channel block to be different from that required for cytochrome
      P450 inhibition. The "IKCa1-pharmacophore" consists of a (2
      halogenophenyl)diphenylmethane moiety substituted by an unsubstituted polar pi
      electron-rich heterocycle (pyrazole or tetrazole) or a -CN group, whereas
      cytochrome P450 inhibition absolutely requires the imidazole ring. A series of
      pyrazoles, acetonitriles, and tetrazoles were synthesized and found to
      selectively block IKCa1. TRAM-34 (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole)
      inhibits the cloned and the native IKCa1 channel in human T lymphocytes with a
      K(d) of 20-25 nM and is 200- to 1,500-fold selective over other ion channels.
      Using TRAM-34, we show that blocking IKCa1 in human lymphocytes, in the absence
      of P450-inhibition, results in suppression of mitogen-stimulated [(3)H]thymidine
      incorporation of preactivated lymphocytes with EC(50)-values of 100 nM-1 microM
      depending on the donor. Combinations of TRAM-34 and cyclosporin A are more
      effective in suppressing lymphocyte mitogenesis than either compound alone. Our
      studies suggest that TRAM-34 and related compounds may hold therapeutic promise
      as immunosuppressants.

PMID- 10884438
TI  - Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in
      diabetic nephropathy.
AB  - Transforming growth factor beta (TGF-beta) has been shown to participate in the
      pathophysiology of diabetic complications. As shown most recently, TGF-beta
      stimulates the expression of a distinct serine/threonine kinase (hSGK) which had
      previously been cloned as an early gene transcriptionally regulated by cell
      volume alterations. The present study was performed to elucidate transcription
      and function of hSGK in diabetic nephropathy. As shown by Northern blotting, an
      increase of extracellular glucose concentration increased hSGK mRNA levels in
      cultured cells, an effect qualitatively mimicked by osmotic cell shrinkage or
      treatment with TGF-beta (2 microgram/liter), phorbol 12,13-didecanoate (1
      microM), or the Ca(2+) ionophore ionomycin (1 microM) and blunted by high
      concentrations of nifedipine (10 and 100 microM). In situ hybridization revealed
      that hSGK transcription was markedly enhanced in diabetic nephropathy, with
      particularly high expression in mesangial cells, interstitial cells, and cells in
      thick ascending limbs of Henle's loop and distal tubules. According to voltage
      clamp and tracer flux studies in Xenopus oocytes expressing the renal epithelial
      Na(+) channel ENaC or the mouse thick ascending limb Na(+),K(+),2Cl(-)
      cotransporter BSC-1, coexpression with hSGK stimulated ENaC and BSC-1 11-fold and
      6-fold, respectively, effects reversed by kinase inhibitors staurosporine (1
      microM) and chelerythrine (1 microM) and not elicited by inactive hSGK. In
      conclusion, excessive extracellular glucose concentrations enhance hSGK
      transcription, which in turn stimulates renal tubular Na(+) transport. These
      observations disclose an additional element in the pathophysiology of diabetic
      nephropathy.

PMID- 10884440
TI  - Stroke: continuity and change.

PMID- 10884439
TI  - The emergence of visual objects in space-time.
AB  - It is natural to think that in perceiving dynamic scenes, vision takes a series
      of snapshots. Motion perception can ensue when the snapshots are different. The
      snapshot metaphor suggests two questions: (i) How does the visual system put
      together elements within each snapshot to form objects? This is the spatial
      grouping problem. (ii) When the snapshots are different, how does the visual
      system know which element in one snapshot corresponds to which element in the
      next? This is the temporal grouping problem. The snapshot metaphor is a
      caricature of the dominant model in the field-the sequential model-according to
      which spatial and temporal grouping are independent. The model we propose here is
      an interactive model, according to which the two grouping mechanisms are not
      separable. Currently, the experiments that support the interactive model are not
      conclusive because they use stimuli that are excessively specialized. To overcome
      this weakness, we created a new type of stimulus-spatiotemporal dot lattices
      which allow us to independently manipulate the strength of spatial and temporal
      groupings. For these stimuli, sequential models make one fundamental assumption:
      if the spatial configuration of the stimulus remains constant, the perception of
      spatial grouping cannot be affected by manipulations of the temporal
      configuration of the stimulus. Our data are inconsistent with this assumption.

PMID- 10884441
TI  - Treatment of cognitive impairment after poststroke depression : a double-blind
      treatment trial.
AB  - BACKGROUND AND PURPOSE: Patients with poststroke major depression have a greater
      severity of cognitive impairment than nondepressed patients even when matched for
      size and location of stroke lesion. Prior treatment studies have consistently
      failed to show an improvement in cognitive function even when poststroke mood
      disorders responded to antidepressant therapy. We examined the response of
      cognitive function to treatment with nortriptyline or placebo in a double-blind
      trial. METHODS: Patients with major (n=33) or minor (n=14) depression
      participated in a double-blind treatment study with nortriptyline or placebo.
      They were examined for change in depressive mood, measured by the Hamilton Rating
      Scale for Depression (HAM-D), and change in cognitive impairment, assessed by the
      Mini-Mental State Examination (MMSE), after treatment with nortriptyline or
      placebo. Cognitive treatment response, as measured by the MMSE, was compared
      between patients whose depression did and did not respond to treatment. RESULTS:
      Patients whose poststroke depression remitted (predominantly associated with
      nortriptyline treatment) had significantly greater recovery in cognitive function
      over the course of the treatment study than patients whose mood disorder did not
      remit (predominantly associated with placebo treatment). CONCLUSIONS: Our
      findings support the contention that poststroke major depression leads to a
      "dementia of depression." Prior studies failed to show an effect of treatment
      because the effect size was too small. Successful treatment of depression may
      constitute one of the major methods of promoting cognitive recovery in victims of
      stroke.

PMID- 10884442
TI  - Vascular dementia : incidence and risk factors in the Canadian study of health
      and aging.
AB  - BACKGROUND AND PURPOSE: Very few population-based studies have systematically
      examined incident vascular dementia (VaD). From the Canadian Study of Health and
      Aging cohort, incidence rates of VaD were determined and risk factors analyzed.
      METHODS: This was a cohort incidence study that followed 8623 subjects presumed
      to be free of dementia over a 5-year period. The risk factors were examined with
      a nested prospective case-control study. Exposure was determined by means of a
      risk factor questionnaire administered to the subject or a proxy at the beginning
      of the study. RESULTS: On the basis of 38 476 person-years at risk, the annual
      incidence rate was estimated to be 2.52 per thousand undemented Canadians (95% CI
      2. 02 to 3.02). Including an estimation of the probability of VaD among the
      decedents, this figure rose to 3.79. For the risk factors study, 105 incident
      cases of VaD according to the NINCDS-AIREN criteria were compared with 802
      control subjects. Significant risk factors were: age (OR=1.05), residing in a
      rural area (2.03), living in an institution (2.33), diabetes (2.15), depression
      (2.41), apolipoprotein E epsilon4 (2.34), hypertension for women (2.05), heart
      problems for men (2.52), taking aspirin (2.33), and occupational exposure to
      pesticides or fertilizers (2.05). Protective factors were eating shellfish (0.46)
      and regular exercise for women (0.46). There was no relation with sex, education,
      or alcohol. CONCLUSIONS: The study confirmed some previously reported risk
      factors but also suggested new ones. It raised concerns about the prescription of
      aspirin and perhaps other factors related to rural life.

PMID- 10884443
TI  - Poststroke dementia : clinical features and risk factors.
AB  - BACKGROUND AND PURPOSE: The goal of the present study was to examine a series of
      putative risk factors of poststroke dementia (PSD), especially those factors
      usually associated with cerebrovascular disease and degenerative dementia, in a
      series of 251 consecutive unselected stroke patients. METHODS: A standard
      protocol was prospectively applied at admission and 3 months after stroke; this
      protocol included clinical, functional, and cognitive assessments, hemogram and
      serum biochemistry, ECG and CT exams, apolipoprotein E and angiotensin-converting
      enzyme genotype, and neuropsychological examination. After a neuropsychological
      examination and an interview with a relative, the following diagnostic criteria
      were used: the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV for
      dementia after stroke, DSM-III-R for previous dementia and dementia stage, and
      Association Internationale pour la Recherche et l'Enseignement en Neurologie
      (NINDS-AIREN) for vascular dementia. RESULTS: Seventy-five cases (30%)
      demonstrated dementia at 3-month follow up; 25 of them (10%) had demonstrated
      dementia before the stroke. Dementia was unrelated to type (ischemic/hemorrhagic)
      or location of stroke, vascular factors (hypertension, diabetes, ischemic heart
      disease, or hypercholesterolemia), apolipoprotein E or angiotensin-converting
      enzyme genotype, and serum homocysteine. Age (odds ratio [OR] 1.1, 95% CI 1.03 to
      1.2), previous nephropathy (OR 6.1, 95% CI 1.5 to 24.3), atrial fibrillation (OR
      4.4, 95% CI 1. 4 to 13.9), low Canadian Neurological Scale score at discharge (OR
      0. 5, 95% CI 0.4 to 0.6), and previous mental decline assessed by the shortened
      Spanish version of the Informant Questionnaire on Cognitive Decline in the
      Elderly (SS-IQCODE; OR 1.2, 95% CI 1.1 to 1. 4) were the correlates of dementia
      in logistic regression analyses. The same risks factors were found when cases
      with previous dementia and with hemorrhagic stroke were excluded. CONCLUSIONS:
      Dementia is frequent after ischemic or hemorrhagic stroke. Age, nephropathy,
      atrial fibrillation, previous mental decline, and stroke severity independently
      contribute to the risk.

PMID- 10884444
TI  - A short screening instrument for poststroke dementia : the R-CAMCOG.
AB  - BACKGROUND AND PURPOSE: The CAMCOG is a feasible cognitive screening instrument
      for dementia in patients with a recent stroke. A major disadvantage of the
      CAMCOG, however, is its lengthy and relatively complex administration for
      screening purposes. We therefore developed the Rotterdam CAMCOG (R-CAMCOG), based
      on the original version. Our aim was to reduce the estimated administration time
      to 15 minutes or less and to retain or perhaps even improve its diagnostic
      accuracy. METHODS: We analyzed the item scores on the CAMCOG of 300 consecutive
      stroke patients, after exclusion of patients with a severe aphasia or lowered
      consciousness level, who were entered in the Rotterdam Stroke Databank. The
      diagnosis of dementia was made independent of the R-CAMCOG score, on the basis of
      clinical examination and neuropsychological test results. The R-CAMCOG was
      constructed in 3 steps. First, items with floor and ceiling effects were removed.
      Next, subscales with no additional diagnostic value were excluded. Finally, we
      removed items that did not contribute to the homogeneity of the subscales. The
      diagnostic accuracy of the R-CAMCOG and the original CAMCOG was determined by
      means of the area under the receiver operating characteristic (ROC) curve.
      RESULTS: In the 3 steps, the number of items was reduced from 59 to 25, divided
      over the subscales orientation, memory (recent, remote, and learning),
      perception, and abstraction. The subscale orientation did not reach significance
      in a logistic regression model but was included in the R-CAMCOG because of its
      high face validity in dementia screening. Internal validation with ROC analysis
      suggests that the R-CAMCOG and the CAMCOG are equally accurate in screening for
      poststroke dementia (area under the curve was 0.95 for both tests). CONCLUSIONS:
      The R-CAMCOG has overcome the disadvantages of the original CAMCOG. It is a
      promising, short, and easy-to-administer screening instrument for poststroke
      dementia. It seems to be sufficiently accurate for this purpose, but the test has
      yet to be validated in a separate, independent study.

PMID- 10884445
TI  - Memory impairment in out-of-hospital cardiac arrest survivors is associated with
      global reduction in brain volume, not focal hippocampal injury.
AB  - BACKGROUND AND PURPOSE: More than 30% of out-of-hospital cardiac arrest (OHCA)
      survivors suffer significant memory impairment. The hippocampus may be vulnerable
      to hypoxic injury during cardiac arrest. The purpose of this study was to
      determine whether selective hippocampal injury is the substrate for this memory
      impairment. METHODS: Seventeen OHCA survivors and 12 patients with uncomplicated
      myocardial infarction were studied. OHCA survivors were divided into those with
      impaired and intact memory. Memory was assessed by use of the Rivermead
      Behavioural Memory Test and Doors and People Test. MRI was used to determine
      intracranial, whole-brain, amygdala-hippocampal complex, and temporal lobe
      volumes. Brain structure was also examined by statistical parametric mapping.
      RESULTS: Left amygdala-hippocampal volume was reduced in memory-impaired OHCA
      victims compared with control subjects (mean 3. 93 cm(3) and 95% CI 3.50 to 4.36
      cm(3) versus mean 4.65 cm(3) and 95% CI 4.37 to 4.93 cm(3); P=0.002). Left
      temporal lobe and whole-brain volumes were also reduced. There were no
      differences in amygdala-hippocampal volume indexed against ipsilateral temporal
      lobe volume. Significant correlations were observed between total brain volume
      and Rivermead Behavioural Memory Test (r=0.56, P<0.05) and Doors and People Test
      (r=0.67, P<0.01) scores in OHCA survivors. Both recall and recognition were
      compromised in memory-impaired subjects. Statistical parametric mapping did not
      detect focal brain abnormalities in these subjects. Global cerebral atrophy was
      confirmed by qualitative assessment. CONCLUSIONS: Memory impairment in OHCA
      survivors is associated with global cerebral atrophy, not selective hippocampal
      damage. Rehabilitation protocols need to account for the global nature of the
      brain injury.

PMID- 10884446
TI  - Corpus callosum atrophy in patients with leukoaraiosis may indicate global
      cognitive impairment.
AB  - BACKGROUND AND PURPOSE: The extent of white matter high-intensity lesions (WMLs)
      on T2-weighted MR images may be an indicator of cognitive impairment, especially
      impairment related to frontal lobe dysfunction. However, it is unclear whether
      the extent of WMLs is an independent predictor of cognitive impairment. In
      patients with extensive WMLs, atrophy of the corpus callosum may be an important
      predictor of global cognitive impairment. The purpose of this study was to
      investigate the relation of the extent of WMLs and callosal size with cognitive
      functions in a patient population with a wide range of extent of WMLs. METHODS:
      We studied 62 patients, aged 49 to 86 years, who underwent MRI because of
      neurological symptoms and were diagnosed as having lacunar stroke or no specific
      neurological disease: 28 with lacunar infarcts and 34 without. Multivariate
      analysis was used to test the independent predictive value of patient age, sex,
      educational level, other medical illness, lacunar infarct, corpus callosum area,
      and extent of WMLs with respect to scores of Mini-Mental State Examination or
      verbal fluency task. RESULTS: Only callosal size and age were significant
      independent predictors of the scores of the Mini-Mental State Examination, while
      only the extent of WMLs was an independent predictor of the score of the verbal
      fluency task. CONCLUSIONS: Callosal atrophy may be an important predictor of
      global cognitive impairment in patients with WMLs, whereas the extent of WMLs per
      se may be related to impairment of frontal lobe function independent of callosal
      atrophy.

PMID- 10884448
TI  - Chlamydia pneumoniae seropositivity is associated with carotid artery intima
      media thickness.
AB  - BACKGROUND AND PURPOSE: Infection may both augment the atherosclerotic process
      and contribute to later manifestations of overt clinical disease. Chlamydia
      pneumoniae elementary bodies have been detected in atherosclerotic lesions. The
      aim of the present study was to investigate whether elevated titers of antibodies
      and circulating immune complexes to C pneumoniae were associated with ultrasound
      findings indicating presence of atherosclerosis in the carotid artery. METHODS:
      Serum titers of antibodies to C pneumoniae (IgM, IgA, IgG, and circulating immune
      complex) were related to intima-media thickness (IMT) and plaque status measured
      by B-mode ultrasound in the carotid artery in 113 men with treated hypertension
      and at least 1 of the following risk factors: hypercholesterolemia, smoking, or
      diabetes. RESULTS: Any of the titers was elevated in 56 (50%) men, and common
      carotid artery IMT was thicker in this group compared with the 57 men without any
      elevated titers (1.00 versus 0.92 mm, P<0.05). There were no accompanying
      differences in blood pressure, lipid levels, blood glucose, or smoking. Elevation
      of separate antibody types and circulation immune complex were also associated
      with increased IMT. In the latter group, systolic blood pressure was higher among
      seropositive patients compared with those who had no circulating immune complex.
      Seropositivity was not related to plaque status. CONCLUSIONS: Seropositivity for
      C pneumoniae was associated with an increased intima-media thickness in the
      common carotid artery but not plaque status in hypertensive men at high risk for
      cardiovascular disease.

PMID- 10884447
TI  - Chlamydia pneumoniae and the risk of first ischemic stroke : The Northern
      Manhattan Stroke Study.
AB  - BACKGROUND AND PURPOSE: Serological evidence of infection with Chlamydia
      pneumoniae has been associated with cardiovascular disease in multiple
      epidemiological studies. The data on its association with ischemic stroke are
      limited. We sought to determine whether chronic C pneumoniae infection is
      associated with ischemic stroke in a multi-ethnic population. METHODS: The
      Northern Manhattan Stroke Study contains a population-based, case-control study
      component. Cases had first ischemic stroke and matched control subjects were
      derived through random digit dialing. Titers of IgG, IgA, and IgM antibodies
      specific for C pneumoniae were measured with the use of microimmunofluorescence,
      and titers >/=1:16 were considered positive. Conditional logistic regression was
      used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) after
      adjustment for medical, behavioral, and socioeconomic factors. RESULTS: Eighty
      nine cases and 89 control subjects were selected. Mean age among cases was 68.5+/
      12.8 years; 53% were women and 15% of the subjects were white, 28% were black,
      and 54% were Hispanic. Elevated C pneumoniae IgA titers were significantly
      associated with risk of ischemic stroke after adjusting for other stroke risk
      factors (adjusted OR 4. 51, 95% CI 1.44 to 14.06). IgG titers were less strongly
      associated with stroke risk (adjusted OR 2.59, 95% CI 0.87 to 7.75). The
      association of IgA with stroke risk was detected in both younger and older
      groups, in men and women, and in whites, blacks, and Hispanics. There was also a
      significant continuous increase in risk associated with the log-transformation of
      the titer for IgA (adjusted OR 1.32, 95% CI 1.05 to 1.66) but not IgG.
      CONCLUSIONS: Serological evidence of chronic infection with C pneumoniae is
      associated with risk of ischemic stroke in an urban, multi-ethnic population. IgA
      titers may be a better marker of this risk than are IgG titers. This association
      is independent of other vascular disease risk factors. Further prospective
      epidemiological studies of the effect of this infection on stroke risk are
      warranted.

PMID- 10884449
TI  - Dietary potassium intake and stroke mortality.
AB  - BACKGROUND AND PURPOSE: An inverse relationship of dietary potassium to stroke
      mortality in a small community has been previously reported. To further assess
      this association in a larger sample, we examined data from the first National
      Health and Nutrition Examination Survey (NHANES I) Epidemiological Follow-up
      Study. METHODS: We analyzed baseline data during 1971-1975 and follow-up through
      1992. Dietary potassium intake, determined by 24-hour dietary recall at baseline,
      was available for 9866 subjects. Stroke mortality was recorded through 1992
      follow-up. RESULTS: Mean age and dietary potassium at baseline were 55 years and
      2084 mg/d; blacks reported significantly lower potassium intake than whites (1606
      versus 2178 mg/24 h). During an average of 16.7 years of follow-up, there were
      304 stroke deaths. For men, stratified by tertile of dietary potassium intake,
      age-adjusted stroke mortality rates per 1000 person-years for the lowest dietary
      potassium group were significantly higher than for the highest intake group, for
      both whites (1.94 versus 1.17; relative risk, 1.66; 95% CI, 1.32 to 2.14) and
      blacks (5.08 versus 1.19; relative risk, 4.27; 95% CI, 1.88 to 9. 19). For women,
      there was no significant difference in stroke mortality between similar levels of
      potassium intake for either whites (1.61 versus 1.42; relative risk, 1.13; 95%
      CI, 0.84 to 1.66) or blacks (2.46 versus 3.04; relative risk, 0.80; 95% CI, 0.21
      to 2. 01). After stratification by hypertensive status, stroke mortality rates
      were significantly different by tertile of dietary potassium only for
      hypertensive men. There was no stroke mortality difference by potassium intake
      among hypertensive women or nonhypertensive men and women. Multivariate analysis,
      in which we controlled for caloric intake and other baseline cardiovascular risk
      factors, revealed that only among black men and hypertensive men was lower
      dietary potassium intake a predictor of stroke mortality. CONCLUSIONS: The
      previous finding of an association of increasing dietary potassium intake with
      decreasing stroke mortality has been detected only among black men and
      hypertensive men in this study.

PMID- 10884450
TI  - Differing temporal patterns of onset in subgroups of patients with intracerebral
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to further analyze the
      temporal patterns of onset of intracerebral hemorrhage (ICH) and to determine
      whether or not subgroups with specific clinical characteristics exhibit different
      patterns of onset. METHODS: The daily, weekly, and yearly variations in
      occurrence of ICH together with the relationship between ICH occurrence and
      changes in air temperature were evaluated in 1018 patients. Patients were grouped
      according to the presumed etiology of ICH: hypertensive ICH, secondary ICH, and
      ICH of undetermined origin. The contribution of demographic and clinical factors
      to the temporal distributions of ICH was also evaluated. RESULTS: Marked
      differences in seasonal and diurnal patterns of ICH onset were observed in the
      different groups. The incidence of hypertensive ICH reflected seasonal and
      circadian changes in blood pressure, whereas the latter did not seem related to
      the onset of nonhypertensive ICH. The seasonal pattern was more evident in
      elderly patients with hypertensive ICH than in younger subjects. No significant
      weekly variations were observed; however, risk was greater on Monday in the
      working population. CONCLUSIONS: Our results suggest that the higher incidence of
      ICH in the colder months is due to the effect of low temperatures on blood
      pressure and that the clustering of ICH events in the morning is due to the
      increase in sympathetic tone, and consequent increase in blood pressure, on
      awakening.

PMID- 10884451
TI  - Reperfusion and metabolic recovery of brain tissue and clinical outcome after
      ischemic stroke and thrombolytic therapy.
AB  - BACKGROUND AND PURPOSE: It is unclear from recent clinical trials whether
      thrombolytic agents are capable of facilitating reperfusion and metabolic
      recovery over time or whether a beneficial effect is counteracted by an increase
      in the risk of brain hemorrhage. We studied the effect of thrombolytic treatment
      on metabolic recovery after reperfusion and clinical outcome. METHODS: Patients
      were prospectively studied with (99m)Tc-ethyl cysteinate dimer single photon
      emission computed tomography ((99m)Tc-ECD-SPECT) before treatment with
      recombinant tissue plasminogen activator (rTPA; 0.9 mg/kg IV; n=26) or placebo
      (n=26) 6 to 8 hours after treatment and at 7+/-1 days. Activity deficits were
      graded, compared between the treatment groups, and correlated with clinical
      outcome and the incidence of brain hemorrhage. Metabolic recovery of ischemic
      brain tissue was defined as a 25% decrease on the SPECT graded scale. RESULTS:
      Patients with metabolic recovery (n=28) had a better chance of being functionally
      unimpaired 3 months after stroke than patients without recovery (n=24) (OR 4.5,
      95% CI 1.09 to 18.89) and had smaller infarcts on follow-up CT (36+/-38 versus
      167+/-162 mL), regardless of whether metabolic recovery was observed within 6 to
      8 hours of treatment or at 7 days. None of the 28 patients with metabolic
      recovery had a fatal parenchymal hemorrhage versus 5 of 24 patients without
      recovery (P=0.016). Treatment did not affect the incidence of brain tissue
      metabolic recovery. CONCLUSIONS: Brain tissue metabolic recovery after ischemic
      stroke was associated with a beneficial effect on clinical outcome and was not
      facilitated by treatment with 0.9 mg of intravenous rTPA.

PMID- 10884452
TI  - One-year follow-Up in acute stroke patients treated with rtPA in clinical
      routine.
AB  - BACKGROUND AND PURPOSE: A recent placebo-controlled study provided evidence of a
      sustained benefit at 1 year from systemic thrombolysis in patients with acute
      ischemic stroke. The scope of the present study is to determine whether
      comparable results may be attained in everyday practice if current management
      guidelines are closely met. METHODS: Between March 1996 and July 1998, 150
      consecutive patients with acute ischemic stroke were treated with systemic
      thrombolysis using alteplase, strictly in accordance with American Heart
      Association (AHA) guidelines. The patients were followed up for 12 months after
      treatment. RESULTS: Baseline characteristics and complication rates were
      comparable to those of the National Institute of Neurological Disorders and
      Stroke (NINDS) study, except for a somewhat younger age (mean 63 years) and lower
      National Institutes of Health Stroke Scale score (median 11). At 1 year, 41% of
      our patients showed minimal or no disability (Rankin scale score of 0 or 1),
      comparable to 41% in the NINDS rtPA group. The overall rate of recurrent stroke
      was 6.6% and the transient ischemic attack rate 3.3% at 1 year. Six patients (4%)
      died after the first 3 months, none of them due to recurrent stroke, and 5 had
      already been severely disabled at 3 months. CONCLUSIONS: These observations
      further encourage the routine use of rtPA for the treatment of acute ischemic
      stroke in strict accordance with the AHA guidelines.

PMID- 10884453
TI  - Streptokinase in acute ischemic stroke: an individual patient data meta-analysis
      : The Thrombolysis in Acute Stroke Pooling Project.
AB  - BACKGROUND AND PURPOSE: Three major randomized controlled trials of streptokinase
      in acute ischemic stroke were curtailed because of safety concerns. The
      prospective Thrombolysis in Acute Stroke Pooling Project (TAS-PP) was established
      to examine the aggregate data to identify factors influencing the effect of
      streptokinase. METHODS: Individual patient data from the Australian Streptokinase
      Trial (ASK), Multicentre Acute Stroke Trial-Europe (MAST-E), Multicentre Acute
      Stroke Trial-Italy (MAST-I), and Glasgow Trial (Glasgow) were pooled.
      Multivariate modeling determined the interaction between treatment effect and
      delay from symptom onset to treatment, predicted baseline risk, age, concomitant
      aspirin or heparin use, and the presence of early CT signs on the outcomes of 10
      day death, death and disability, or death alone at 3 or 6 months. RESULTS:
      Patients' records were pooled (total 1292 patients; streptokinase, n=653, no
      streptokinase n=639). The subgroup analysis of treatment effect according to
      delay from symptoms to inclusion shows only a trend toward a better treatment
      effect with shorter delay, which is not statistically significant for any
      outcome. Heavier patients in MAST-E may have had a lower (non significant) risk
      from the fixed dose of 1.5 million units of streptokinase. Concomitant aspirin
      increased the excess mortality rates in streptokinase-treated patients (17%
      without aspirin versus 91% with aspirin, P=0.005). The presence of early CT scan
      signs did not increase the detrimental effect of streptokinase. CONCLUSIONS: Few
      factors influenced the response to streptokinase. However, earlier
      administration, lower doses of streptokinase, and avoidance of concomitant
      aspirin should be considered if further streptokinase trials in acute stroke are
      planned.

PMID- 10884454
TI  - Vasodilatory response of border zones to acetazolamide before and after
      endarterectomy : an echo planar imaging-dynamic susceptibility contrast-enhanced
      MRI study in patients with high-grade unilateral internal carotid artery
      stenosis.
AB  - BACKGROUND AND PURPOSE: The importance of hemodynamic changes related to a high
      grade internal carotid artery (ICA) stenosis remains a matter of controversy.
      Areas between the vascular territories of major cerebral arteries, namely, the
      border zones, may be selectively vulnerable to hemodynamic alteration. The aim of
      this study was to search for any hemodynamic impact of carotid endarterectomy
      (CEA) on vasodilatory response, in particular, within the border zones, by means
      of multislice dynamic susceptibility contrast MRI. METHODS: Thirteen patients
      with a high-grade unilateral ICA stenosis (>80%) were examined. Relative regional
      cerebral blood volume (rrCBV) was determined separately for white matter, gray
      matter, and anterior and posterior border zones by the acetazolamide test. A
      vasomotor reactivity index was evaluated from the rrCBV values. Values from the
      ipsilateral hemisphere were compared with contralateral ones, before and after
      CEA. RESULTS: Before CEA, rrCBV values in the anterior border zones were
      significantly (P<0.05) higher in the ipsilateral hemisphere than in the
      contralateral hemisphere. A decrease in vasomotor reactivity indexes was also
      observed in the lesion side, but the difference from the contralateral side was
      not statistically significant. In posterior border zones, no differences in rrCBV
      or vasomotor reactivity were found between the ipsilateral and the contralateral
      hemispheres. After CEA, the rrCBV asymmetry in the anterior border zones cleared.
      CONCLUSIONS: High-grade ICA stenosis with efficient primary collateral pathways
      may have an early limited hemodynamic impact within border-zone areas. The
      favorable course of these abnormalities after surgery suggests an additional
      benefit of CEA at this stage.

PMID- 10884455
TI  - Perioperative and late stroke rates of carotid endarterectomy contralateral to
      carotid artery occlusion : results from a randomized trial.
AB  - BACKGROUND AND PURPOSE: Several previous studies have reported the benefits of
      carotid endarterectomy (CEA) contralateral to carotid occlusion with mixed
      results, but none of these were randomized except for the North American
      Symptomatic Carotid Endarterectomy Trial. The purpose of this study was to
      analyze the results of surgery in patients with contralateral carotid artery
      occlusion in a randomized trial in which randomization was done according to the
      method of closure. METHODS: In 399 CEAs (357 patients) that were randomized into
      primary closure versus patching, 49 had contralateral occlusion. Strokes were
      designated as ipsilateral if they arose from the same CEA side and contralateral
      if they arose from the occluded side. A Kaplan-Meier analysis was used to
      estimate perioperative strokes and stroke-free survival in patients with
      contralateral occlusion (group A) versus those without contralateral occlusion
      (group B). RESULTS: Demographic characteristics and mean follow-up for both
      groups were similar (group A, 40 months; group B, 33 months). Group A had a
      higher incidence of contralateral transient ischemic attacks (TIAs) (12.2% versus
      0.9%; P<0.0001), contralateral strokes (2% versus 0%; P=0.025), and combined
      contralateral TIAs/strokes (14.3% versus 0.9%; P<0.0001). The rates for
      perioperative and all strokes (operative and late) were 2% and 4. 1% (2%
      ipsilateral and 2% contralateral strokes) for group A and 2. 9% and 3.4% (all
      ipsilateral) for group B (P=0.60 and 0.85, respectively). The rates for
      perioperative and all TIAs were 0% and 14.3% for group A versus 2.6% and 6.3% for
      group B (P=0.918 and P=0. 08, respectively). The rates for perioperative and all
      neurological events (TIA and stroke) were 2% and 18.4% for group A and 5.4% and
      9. 7% for group B (P=0.27 and 0.113, respectively). The cumulative stroke-free
      survival rates at 5 years were 84% for group A and 77% for group B (P>0.1). The
      cumulative stroke-free survival rates at 5 years for symptomatic and asymptomatic
      patients in group A and group B were also similar. The perioperative and late
      deaths were similar for both groups (group A, 8%; group B, 14%). CONCLUSIONS:
      Group A had a higher incidence of contralateral TIAs and strokes than group B;
      however, the perioperative and all late stroke rates and survival rates of CEA
      were comparable in patients with and without contralateral occlusion.

PMID- 10884456
TI  - Stroke, a major and increasing risk factor for femoral neck fracture.
AB  - BACKGROUND AND PURPOSE: Patients with stroke have up to a 4-fold increased risk
      of hip fracture because of their high incidence of falls and loss of bone mass in
      the paretic side, ie, hemiosteoporosis. The purpose of this study was to
      investigate the prevalence of previous stroke among patients with femoral neck
      fracture. METHODS: The study included all 568 patients, aged >/=65 years, who
      underwent surgery for femoral neck fracture in 1980, 1983, 1987, 1993, and 1997
      at the orthopedic clinic of Umea University Hospital, Umea, Sweden. RESULTS: The
      prevalence of previous strokes ranged from 16.4% to 38.5% (P<0.001); this finding
      is only partly explained by the increased incidence of stroke in the
      corresponding population, and there was no significant increase in the overall
      incidence of femoral neck fracture. Fractures occurred 5.4+/-6.4 years after
      stroke (median 2.9 years, range 0 to 33 years). In stroke patients with
      unilateral stroke and persisting paresis at the time of fracture, 62.5% had their
      fracture on the paretic side (P=0. 034). Survival was significantly reduced in
      patients with previous stroke (P<0.001). In patients previously independently
      mobile, 69.2% with no previous stroke and 38.1% with previous stroke were still
      mobile at discharge from the orthopedic unit (P<0.001). CONCLUSIONS: Attention
      must be focused on stroke as a major and increasing risk factor for femoral neck
      fracture and also on the poor postfracture outcome and reduced survival of these
      patients. Prevention of poststroke fractures is necessary and is aimed at
      reducing the risk of poststroke fall and preventing the development of
      hemiosteoporosis.

PMID- 10884457
TI  - Acute ischemic stroke : polymorphonuclear leukocyte membrane fluidity and
      cytosolic Ca(2+) concentration at baseline and after chemotactic activation.
AB  - BACKGROUND AND PURPOSE: Several reports have considered the role of systemic
      leukocytes in acute ischemic stroke (AIS). Initially, greater attention was
      focused on the leukocyte count and subsequently on their adhesiveness,
      aggregation, rheology, and activation. The aim of this study was the evaluation
      of certain polymorphonuclear leukocyte (PMN) parameters, reflecting their
      rheology and activation, in subjects with AIS. METHODS: In a group of 19 subjects
      with AIS and in a control group of 18 subjects with asymptomatic vascular
      atherosclerotic disease, we evaluated the PMN membrane fluidity and cytosolic
      Ca(2+) concentration at baseline and after in vitro chemotactic activation with 4
      phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine
      (fMLP). RESULTS: From the obtained data, it is evident that at baseline only PMN
      membrane fluidity distinguishes control subjects from AIS subjects. After PMN
      activation with PMA and fMLP, prolonged for 5 and 15 minutes, we found an
      increase in PMN cytosolic Ca(2+) concentration and a decrease in PMN membrane
      fluidity only in subjects with AIS. CONCLUSIONS: These findings emphasize that in
      subjects with AIS a functional alteration of systemic PMN cells is clearly
      expressed during chemotactic activation, although the mechanism of this
      abnormality is not yet explained.

PMID- 10884458
TI  - Trends in stroke incidence and acute case fatality in a Japanese rural area : the
      Oyabe study.
AB  - BACKGROUND AND PURPOSE: Stroke mortality in Japan has significantly declined
      during recent decades. To determine the cause of this decrease, we studied the
      trends in stroke incidence and case fatality within 28 days after stroke in a
      rural area in Japan. METHODS: We used a population-based registry during 1977
      1991 in Oyabe, a rural area in the central part of Japan. The average population
      aged 25 years and older numbered 32 859 persons. Changes in age-standardized
      stroke incidence rate were calculated and compared between the 3 periods 1977
      1981, 1982-1986, and 1987-1991. The 28-day case fatality rate was evaluated and
      also compared between the 3 periods by onset year. RESULTS: The total number of
      strokes was 2068. The age-standardized incidence rate of all strokes decreased
      during the 15-year period, from 605 to 417 per 100 000 in men and from 476 to 329
      per 100 000 in women. A marked decline was found during 1977-1986 but was not
      apparent during 1987-1991. Moreover, there was an increase in the group aged 75
      years and older. The 28-day case fatality rates for all strokes improved from
      18.0% to 14.2% in men and from 26.8% to 19.1% in women during the observation
      period. CONCLUSIONS: These data indicate that declines in the stroke incidence
      and the 28- day case fatality have been associated with a marked decrease in
      stroke-related mortality in Japan.

PMID- 10884459
TI  - International trends in mortality from stroke, 1968 to 1994.
AB  - BACKGROUND AND PURPOSE: The World Health Organization data bank is an invaluable
      source of information for international comparison of mortality trends. We
      present rates and trends in mortality from stroke up to 1994, with a particular
      emphasis on the last 10-year period. Data are presented for men and women in 51
      industrialized and developing countries from different parts of the world.
      METHODS: We included all deaths from cerebrovascular disease for the population
      aged 35 to 84 years from all the countries in which death certificates were
      estimated to be available for at least 80% for the period from 1968 to 1994. Age
      standardized mortality rates from stroke were calculated for each country for the
      last available 5 years. Time trends were calculated by using ordinary linear
      regression and are presented for the entire study period and for 3 separate time
      periods: 1968 to 1974, 1975 to 1984, and 1985 to 1994. The last 10-year period
      was further subdivided into 2 parts of 5 years each. We analyzed data separately
      for men and women and for groups aged 35 to 74 years and 75 to 84 years. RESULTS:
      The highest rates at the end of the study period for the population aged 35 to 74
      years were observed in eastern Europe and previous Soviet Union countries (309 to
      156/100 000 per year among men and 222 to 101/100 000 per year among women),
      Mauritius (268/100 000 per year among men and 138/100 000 per year among women),
      and Trinidad and Tobago (185/100 000 per year among men and 134/100 000 per year
      among women). Relatively low to average rates (<100/100 000 per year among men
      and <70/100 000 per year among women) were reported for Western Europe, with an
      exception of Portugal (162/100 000 per year among men and 95/100 000 per year
      among women). The countries with lowest stroke mortality rates at the end of the
      study period, such as the United States, Canada, Switzerland, France, and
      Australia, experienced steep declining trends. However, the slope of the decline
      was substantially reduced during the last 5 years in these countries. Mortality
      from stroke increased most in the eastern European countries, especially during
      the last 5 years. Among other high-risk populations, no change in stroke
      mortality trends was observed in Mauritius, whereas somewhat declining trends
      were seen in Trinidad and Tobago. CONCLUSIONS: We observed large differences in
      mortality rates from stroke around the world together with a wide variation in
      mortality trends. A widening gap was observed between 2 groups of nations, those
      with low and declining stroke mortality rates and those with high and increasing
      mortality, in particular, between western and eastern Europe. Eastern European
      countries should initiate actions aiming at the reduction of stroke risk, perhaps
      by looking at the examples of Japan and Finland and the other countries that have
      been the most successful in reducing previously very high mortality from stroke.

PMID- 10884460
TI  - Validity of self-reported stroke : The Tromso Study.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to validate the diagnosis of
      self-reported stroke. METHODS: During 1994-1995, 27 159 people attended a
      population health survey in the community of Tromso, Norway, a response rate of
      77%. A total of 418 attenders reported a history of stroke. In 1997, all
      individuals with a self-reported stroke who were still living in the community
      (n=362) were invited to a clinical reexamination. For each of the 269 people who
      were reexamined, a person who reported no history of stroke was selected and was
      reexamined in the same way. RESULTS: On the basis of the reexamination, 213
      (79.2%) of the self-reported strokes were confirmed. Thirteen individuals (4.8%)
      had a possible stroke. The remaining 43 individuals had either transient ischemic
      attack (TIA; n=18), traumatic head injuries (n=16), or perinatal cerebral damage,
      complicated migraine, syncope, possible TIA, or cerebral aneurysm without
      bleeding (n=9). Among the confirmed strokes, 30 (14.1%) were hemorrhagic and 118
      (55.4%) were thromboembolic. Of the 30 hemorrhages, 16 were subarachnoidal
      bleedings, 10 due to ruptured aneurysms. The histories of stroke, including both
      the symptoms and the signs, often had a paucity of details and precision, making
      it impossible to classify 65 stroke victims (30.5%) into stroke subtypes. The
      positive predictive value (PPV) of a self-reported stroke was 0.79. The PPV was
      significantly (P=0.016) greater in men (0.88) than in women (0.73). Individuals
      older than 60 years had a significantly greater PPV than those younger than 60
      years (PPV 0.83 and 0.73, respectively; P=0.05). Hypertension was associated with
      a greater PPV, whereas a history of either ischemic heart disease, diabetes
      mellitus, lung disease, or depression had no impact on the PPV. The estimated
      sensitivity of self-reported stroke in the survey population was approximately
      80% and the specificity was 99%. CONCLUSIONS: We conclude that a self
      administered questionnaire can be used to assess the prevalence of stroke in
      epidemiological research.

PMID- 10884461
TI  - Orthostatic tolerance, cerebral oxygenation, and blood velocity in humans with
      sympathetic failure.
AB  - BACKGROUND AND PURPOSE: Patients with orthostatic hypotension due to sympathetic
      failure become symptomatic when standing, although their capability to maintain
      cerebral blood flow is reported to be preserved. We tested the hypothesis that in
      patients with sympathetic failure, orthostatic symptoms reflect reduced cerebral
      perfusion with insufficient oxygen supply. METHODS: This study addressed the
      relationship between orthostatic tolerance, mean cerebral artery blood velocity
      (V(mean), determined by transcranial Doppler ultrasonography), oxygenation
      (oxyhemoglobin [O(2)Hb], determined by near-infrared spectroscopy), and mean
      arterial pressure at brain level (MAP(MCA), determined by finger arterial
      pressure monitoring [Finapres]) in 9 patients (aged 37 to 70 years; 4 women) and
      their age- and sex-matched controls during 5 minutes of standing. RESULTS: Supine
      MAP(MCA) (108+/-14 versus 86+/-14 mm Hg) and V(mean) (84+/-21 versus 62+/-13 cm.
      s(-1)) were higher in the patients. After 5 minutes of standing, MAP(MCA) was
      lower in the patients (31+/-14 versus 72+/-14 mm Hg), as was V(mean) (51+/-8
      versus 59+/-9 cm. s(-1)), with a larger reduction in O(2)Hb (-11. 6+/-4 versus 
      6.7+/-4.5 micromol. L(-1)). Four patients terminated standing after 1 to 3.5
      minutes. In these symptomatic patients, the orthostatic fall in V(mean) was
      greater (45+/-6 versus 64+/-10 cm. s(-1)), and the orthostatic decrease in O(2)Hb
      (-12.0+/-3.3 versus -7.6+/-3.9 micromol. L(-1)) tended to be larger. The
      reduction in MAP(MCA) was larger after 10 seconds of standing, and MAP(MCA) was
      lower after 1 minute (25+/-8 versus 40+/-6 mm Hg). CONCLUSIONS: In patients with
      sympathetic failure, the orthostatic reduction in cerebral blood velocity and
      oxygenation is larger. Patients who become symptomatic within 5 minutes of
      standing are characterized by a pronounced orthostatic fall in blood pressure,
      cerebral blood velocity, and oxygenation manifest within the first 10 seconds of
      standing.

PMID- 10884462
TI  - Cerebral oxygenation declines in healthy elderly subjects in response to assuming
      the upright position.
AB  - BACKGROUND AND PURPOSE: With increasing age, assuming the upright position is
      more often accompanied by symptoms such as dizziness and lightheadedness,
      possibly as a result of a diminished oxygen supply to the brain due to impaired
      cerebral autoregulation. We aimed to quantify postural changes in cerebral
      oxygenation and systemic hemodynamics in healthy elderly and young subjects.
      METHODS: In 18 healthy elderly subjects (aged 70 to 83 years) and 10 healthy
      young subjects (aged 22 to 45 years), frontal cortical oxygenation and
      hemodynamic responses were continuously monitored by near infrared spectroscopy
      and Finapres, respectively, before and during 10 minutes of active standing.
      RESULTS: -Cortical oxyhemoglobin concentration [O(2)Hb] decreased by -4.6+/-2.2
      micromol/L (P<0.001) and cortical deoxyhemoglobin concentration increased by
      1.5+/-2.4 micromol/L (P<0.05) in the elderly subjects after posture change,
      whereas these variables did not change significantly in the young subjects. The
      postural hemodynamic changes tended to be attenuated in the elderly subjects,
      except for the increases in systolic blood pressure (BP). Smaller postural
      increases in diastolic BP were related to larger [O(2)Hb] decreases (r=0.53,
      P<0.01, corrected for the age effect). CONCLUSIONS: Assuming the upright position
      evokes an asymptomatic decrease in frontal cortical oxygenation in healthy
      elderly subjects but not in healthy young subjects. Cortical [O(2)Hb] changes are
      affected by diastolic BP changes. These findings may indicate that regulation of
      cerebral oxygenation alters with increasing age.

PMID- 10884463
TI  - Impact of cerebral microcirculatory changes on cerebral blood flow during
      cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Cerebral microcirculatory changes during cerebral
      vasospasm after aneurysmal subarachnoid hemorrhage (SAH) are still controversial
      and uncertain. The aim of this study was to investigate the changes of cerebral
      microcirculation during cerebral vasospasm and to clarify the roles of
      microcirculatory disturbances in cerebral ischemia by measuring cerebral
      circulation time (CCT) and regional cerebral blood flow (rCBF). METHODS: In 24
      cases with aneurysmal SAH, rCBF studies by single-photon emission CT and digital
      subtraction angiography (DSA) were performed on the same day between 5 and 7 days
      after SAH and/or within 4 hours after the onset of delayed ischemic neurological
      deficits. CCT was obtained by analyzing the time-density curve of the contrast
      media on DSA images and was divided into proximal CCT, which was the circulation
      time through the extraparenchymal large arteries, and peripheral CCT, which was
      the circulation time through the intraparenchymal small vessels. They were
      analyzed in association with rCBF and angiographic vasospasm. RESULTS: Severe
      angiographic vasospasm statistically decreased rCBF, and correlation between the
      degree of angiographic vasospasm and rCBF was seen (r=0.429, P=0.0006).
      Peripheral CCT showed strong inverse correlation with rCBF (r=-0.767, P<0.0001).
      Even in none/mild or moderate angiographic vasospasm, prolonged peripheral CCT
      was clearly associated with decreased rCBF. CONCLUSIONS: In addition to the
      marked luminal narrowing of large arteries detected as severe angiographic
      vasospasm, microcirculatory changes detected as prolonged peripheral CCT affected
      cerebral ischemia during cerebral vasospasm. These results suggested that
      impaired autoregulatory vasodilation or decreased luminal caliber in
      intraparenchymal vessels may take part in cerebral ischemia during cerebral
      vasospasm.

PMID- 10884464
TI  - Genetic variants of platelet glycoprotein receptors and risk of stroke in young
      women.
AB  - BACKGROUND AND PURPOSE: A number of studies have examined the relationship
      between genetic platelet glycoprotein variants and early-onset atherothrombotic
      disease, particularly acute myocardial infarction. Data on the association of
      these genetic susceptibility markers with ischemic stroke are more limited, and
      their role in hemorrhagic stroke has not been previously examined. METHODS: We
      performed genotype analysis for 5 common diallelic platelet glycoprotein
      polymorphisms in a population-based study of 78 white women aged <45 years with
      arterial stroke (36 ischemic cases and 42 hemorrhagic cases) and 346
      demographically similar control subjects. RESULTS: The 807T variant of
      glycoprotein Ia was associated with a 2-fold increased risk of ischemic stroke
      (age-adjusted odds ratio [OR]=2.24; 95% CI=0.99 to 5.06). The Met(145) allele of
      glycoprotein Ibalpha was associated with a trend toward an increased risk of
      ischemic stroke that was more pronounced in the homozygous state (OR=10.36), but
      the CI is extremely wide because of the small numbers of subjects (95% CI=1.43 to
      79.34). Homozygosity for the Ser(843) allele of the glycoprotein IIb was
      associated with an approximately 5-fold increased risk of ischemic stroke among
      subgroups of women who carried a diagnosis of hypertension or diabetes (OR=4.51;
      95% CI=1.01 to 20.13) or had elevated plasma homocysteine levels (OR=5.94; 95%
      CI=1.53 to 23.05). The genotype distributions for all 5 platelet glycoprotein
      polymorphisms were similar among hemorrhagic stroke cases and controls.
      CONCLUSIONS: Several inherited platelet glycoprotein variants may be associated
      with an increased risk of ischemic stroke in young women. These associations
      seemed to be confined to women with other cardiovascular risk factors. Additional
      studies involving larger numbers of subjects are needed to confirm these
      preliminary findings.

PMID- 10884465
TI  - Association between the Glu298Asp polymorphism in the endothelial constitutive
      nitric oxide synthase gene and brain infarction. The GENIC Investigators.
AB  - BACKGROUND AND PURPOSE: Nitric oxide (NO) synthesized by endothelial constitutive
      NO synthase (ecNOS) plays a key role in vascular regulation and atherosclerosis.
      Little is known concerning the role of the ecNOS gene (NOS3) as a risk factor for
      brain infarction (BI). Our aim was to investigate the relation between the
      Glu298Asp polymorphism in exon 7 of NOS3 with BI and its subtypes. METHODS:
      Patients (n=460; cases) with BI were consecutively recruited and classified into
      etiological subtypes. Control subjects (n=460; controls) without a history of
      stroke were recruited among individuals hospitalized at the same institutions and
      individually matched on age, sex, and center. Genotypes of the polymorphism were
      determined by polymerase chain reaction. RESULTS: The distribution of genotypes
      was significantly different between cases and controls (P=0.008); the GG genotype
      was more frequent in cases (46.1%) than in controls (35.4%; OR, 1.56; 95% CI,
      1.19 to 2.04). Among subtypes, the frequency of the GG genotype was significantly
      higher in cases than in controls in the lacunar subtype (OR, 2.00; 95% CI, 1.05
      to 3. 80); in this group, the relation between BI and LDL level was stronger
      among carriers of the GG genotype than among noncarriers (P for interaction,
      0.05). CONCLUSIONS: Homozygosity for the G allele of the Glu298Asp polymorphism
      in NOS3 was associated with BI, and especially with lacunar stroke. Our findings
      suggest that genetic susceptibility and LDL cholesterol have a synergistic
      relation. Although these findings should be replicated in a larger sample of
      subjects and the functionality of the Glu298Asp polymorphism has not been
      established, these results may help us to understand the cause of the
      arteriolopathy underlying lacunae and have future implications in their treatment
      and prevention.

PMID- 10884466
TI  - Contrast transcranial doppler ultrasound in the detection of right-to-left shunts
      : time window and threshold in microbubble numbers.
AB  - BACKGROUND AND PURPOSE: Cardiac right-to-left shunts can be identified by
      transesophageal echocardiography (TEE) and by transcranial Doppler ultrasound
      (TCD) with the use of contrast agents and a Valsalva maneuver (VM) as provocation
      procedure. Currently, data on the appropriate timing of the VM, the use of a
      diagnostic time window, and a threshold in contrast agent microbubbles detected
      are insufficient. METHODS: Fifty-eight patients were investigated by both TEE and
      bilateral TCD of the middle cerebral artery. The following protocol with
      injections of 10 mL of the commercial galactose-based contrast agent Echovist was
      applied in a randomized way: (1) no VM, (2) VM for 5 seconds starting 2 seconds
      after the beginning of contrast injection, (3) VM for 5 seconds starting 5
      seconds after the beginning of contrast injection, (4) VM for 5 seconds starting
      8 seconds after the beginning of contrast injection, and (5) repetitive short VMs
      in between 2 and 13 seconds after the beginning of contrast injection. In
      addition to the single tests, we also tested the sensitivity and specificity of
      combined results of the tests with VM. RESULTS: In 21 patients, a right-to-left
      shunt was demonstrated by TEE and contrast TCD (shunt positive). Twenty-one
      patients were negative in both investigations, no patient was positive on TEE and
      negative on TCD, and 16 patients were only positive on at least 1 TCD
      investigation but negative during TEE. Test 3 was the most appropriate test when
      combined with the results of 1 of the other tests with VM. The highest
      sensitivities were achieved with a diagnostic time window of 40 seconds and when
      the presence of a single microbubble was sufficient for the diagnosis of a shunt.
      CONCLUSIONS: TCD performed twice with 2 provocation maneuvers with Echovist is a
      sensitive method to identify TEE-proven cardiac right-to-left shunts. The VM
      should be performed for 5 seconds starting at 5 seconds after the beginning of
      contrast injection.

PMID- 10884467
TI  - Assessment of lacunar hemorrhage associated with hypertensive stroke by echo
      planar gradient-echo T2*-weighted MRI.
AB  - BACKGROUND AND PURPOSE: Echo-planar gradient-echo T2*-weighted MR imaging (GRE
      EPI) may detect hypointense lesions representing microhemorrhages with high
      sensitivity. The aim of this study was to evaluate the effectiveness of GRE-EPI
      for detecting old lacunar hemorrhages in hypertensive patients with stroke.
      METHODS: GRE-EPI was performed with a 1.5-T MRI system in 198 hypertensive
      patients with stroke (130 patients with hemorrhagic stroke and 68 patients with
      multiple lacunar stroke) and 66 age-matched healthy elderly individuals. RESULTS:
      Concomitant hypointense foci were found in 84 (66%) patients with hemorrhagic
      stroke, 46 (68%) patients with multiple lacunar stroke, and 3 (5%) healthy
      elderly individuals. These hypointense foci were noted in the lentiform nucleus
      in 61 (47%) patients with hemorrhagic stroke, in the caudate nucleus in 9 (7%)
      patients, in the thalamus in 54 (42%) patients, in the corticosubcortical region
      in 57 (44%) patients, in the brain stem in 40 (34%) patients, and in the
      cerebellum in 32 (25%) patients. CONCLUSIONS: GRE-EPI is effective for the
      detection of lacunar hemorrhages induced by hypertension.

PMID- 10884468
TI  - Three-dimensional ultrasound observation of carotid artery plaque ulceration.
AB  - BACKGROUND AND PURPOSE: Carotid artery plaque ulceration is associated with an
      increased risk of cerebral embolism. However, because of the rather poor
      diagnostic quality of conventional 2-D ultrasound and angiography compared with
      the evaluation of pathological specimens, little information exists on the
      natural course of carotid plaque ulceration. Recently, the introduction of 3-D
      ultrasound has made reproducible investigation of plaque morphology possible,
      providing a reliable plaque surface analysis. METHODS: We performed 3-D
      ultrasound examinations of 17 carotid artery plaques with an ulcerated surface in
      a prospective study of 16 patients (10 men, 6 women; mean+/-SD age 68.9+/-7.1
      years) over a mean observation period of 17.6+/-6.3 months. Exactly parallel B
      mode ultrasound scans (slice distance 0.1 mm) were acquired with a 5-MHz linear
      array probe clamped in a carriage device and driven by a mechanical step motor.
      The recorded images were reconstructed into a volumetric data set in a Cartesian
      coordinate system. RESULTS: At the end of the observation period, surface
      configuration had changed in 4 cases (23.5%). Plaque ulceration regressed in 3
      cases, whereas ulcer progression occurred in 1 case. The remaining 13 plaques
      (76. 5%) showed an unchanged surface configuration. CONCLUSIONS: Through the use
      of 3-D ultrasound, it is possible to noninvasively examine the regression and
      progression of carotid artery plaque ulceration.

PMID- 10884469
TI  - Collateral variations in circle of willis in atherosclerotic population assessed
      by means of transcranial color-coded duplex ultrasonography.
AB  - BACKGROUND AND PURPOSE: Transcranial color-coded duplex ultrasonography combined
      with common carotid artery (CCA) compression can be used to assess the collateral
      function of the circle of Willis. The aim of this study was to assess the unknown
      fraction of hemodynamic functional anterior and posterior communicating arteries
      (AcoA and PcoA, respectively) in an atherosclerotic population with no
      cerebrovascular symptoms. METHODS: In 76 patients with a mean age of 61 (35 to
      89) years, the blood flow velocity changes in the precommunicating parts (A1 and
      P1, respectively) of the anterior and posterior cerebral arteries were measured
      during CCA compression. The AcoA was defined as functional if blood flow was
      reversed in the ipsilateral A1 and enhanced in the contralateral A1 during CCA
      compression. The PcoA was defined as functional if the flow velocity in the P1
      was enhanced >20% during ipsilateral CCA compression. RESULTS: It was possible to
      assess cross flow through the anterior part of the circle of Willis in 95% of the
      subjects. Failure of this collateral pathway was caused by a hypofunctional AcoA
      in 4% and a hypofunctional A1 in 1% of the subjects. Anomalies in the posterior
      part of the circle of Willis hampering collateral flow from the basilar to the
      internal carotid artery were found in 45% of the hemispheres. Thirty-eight
      percent of PcoAs were hypofunctional, and 7% of the posterior cerebral arteries
      had a persistent fetal anatomy. CONCLUSIONS: We found that in subjects with no
      cerebrovascular symptoms, the anterior collateral pathway of the circle of Willis
      was nearly always functional. In contrast, the posterior collateral pathway was
      nonfunctional in almost half of the total number of hemispheres. Comparing these
      basic data with data from patients with cerebral ischemic disease might further
      help to elucidate the importance of the collateral capacity of the circle of
      Willis.

PMID- 10884470
TI  - Stimulated acoustic emission detected by transcranial color doppler ultrasound :
      a contrast-specific phenomenon useful for the detection of cerebral tissue
      perfusion.
AB  - BACKGROUND AND PURPOSE: Experimental and clinical data suggest that insonation of
      echo-contrast agents with high acoustical power produces disintegration of
      microbubbles, resulting in a pseudo-Doppler phenomenon called stimulated acoustic
      emission (SAE). The purpose of this study was to investigate whether SAE might be
      detected by transcranial color Doppler imaging and whether these signals might be
      used for cerebral tissue perfusion measurements. METHODS: Nonmoving microbubbles
      (SHU 563 A) were insonated in vitro through the temporal parts of a human cadaver
      skull, and contrast signals were detected by velocity-coded color Doppler and
      power Doppler recordings. Transcranial color as well as power Doppler
      investigations were performed in 10 healthy volunteers with the echo-contrast
      agent Levovist (SHU 508 A). RESULTS: Color Doppler signals indicating SAE were
      observed in vitro and in transcranial human investigations. These signals were
      characterized by a mosaic of color Doppler pixels ranging over the full color
      scale. Apparent velocity information and spatial distribution of SAE signals
      changed from image frame to image frame. In the experimental model, the intensity
      of SAE signals decreased exponentially over time. With an increase of acoustic
      power, there was a significant increase of the maximum signal intensity (P<0.01)
      and a significantly shortened signal duration (P<0.01), consistent with stronger
      and more rapid disintegration. In humans, SAE signals were clearly detected in
      cerebral tissue regions. The intensity of SAE signals in those regions (eg,
      temporal cortex, 3.7+/-1.2 dB) was approximately 8 times lower than the signal
      enhancement in the major cerebral arteries (eg, in the MCA, 29.5+/-5.6).
      CONCLUSIONS: Echo-contrast specific color Doppler signals known as SAE are
      detectable by transcranial color and power Doppler sonography. Signals due to SAE
      might represent tissue perfusion, thereby providing a method for imaging flow
      with transcranial ultrasound.

PMID- 10884471
TI  - Detection of early CT signs of >1/3 middle cerebral artery infarctions :
      interrater reliability and sensitivity of CT interpretation by physicians
      involved in acute stroke care.
AB  - BACKGROUND AND PURPOSE: This study had 2 goals: (1) to assess interrater
      reliability of academic neuroradiologists when classifying acute infarction by CT
      scan as >1/3 middle cerebral artery (MCA) involvement, <1/3 MCA involvement, or
      no infarction and (2) to determine the sensitivity of physicians potentially
      involved in acute stroke treatment in detecting >1/3 MCA acute infarctions.
      Studies of tissue plasminogen activator show an association between early signs
      of major infarction and poor outcome. The American Academy of Neurology and the
      American Heart Association recommend avoiding thrombolysis if early signs of
      major infarction are present. METHODS: We presented 25 scans (normals, acute
      infarctions, and old infarctions) to 3 academic neuroradiologists. A scoring
      sheet based on Alteplase Thrombolysis for Acute Noninterventional Therapy in
      Ischemic Stroke (ATLANTIS)/CT Summit criteria was used to determine >1/3 MCA
      territory involvement. Nine of the 25 scans were presented again to assess
      intrarater reliability. We recalculated results of our previous study in which
      physicians interpreted infarction scans, now designating the scans as >1/3 MCA,
      <1/3 MCA, or normal, as determined by the neuroradiologists. RESULTS: All 3
      neuroradiologists agreed on no infarction, <1/3 MCA, and >1/3 MCA on 64% of the
      scans. Neuroradiologist test-retest agreement was 96% for >1/3 MCA territory.
      Overall sensitivity for emergency physicians, neurologists, and general
      radiologists for detecting the presence of infarction in scans rated as >1/3 MCA
      was 78%. CONCLUSIONS: Neuroradiologists can achieve moderate agreement in
      detecting >1/3 MCA infarction. The emergency physicians, neurologists, and
      general radiologists tested were reasonably skilled at detecting >1/3 MCA acute
      infarction. However, their performance did not reliably identify all patients who
      have early CT infarct signs that place them at increased risk for cerebral
      hemorrhage after thrombolytic therapy.

PMID- 10884472
TI  - MRI measures of middle cerebral artery diameter in conscious humans during
      simulated orthostasis.
AB  - BACKGROUND AND PURPOSE: The relationship between middle cerebral artery (MCA)
      flow velocity (CFV) and cerebral blood flow (CBF) is uncertain because of unknown
      vessel diameter response to physiological stimuli. The purpose of this study was
      to directly examine the effect of a simulated orthostatic stress (lower body
      negative pressure [LBNP]) as well as increased or decreased end-tidal carbon
      dioxide partial pressure (P(ET)CO(2)) on MCA diameter and CFV. METHODS: Twelve
      subjects participated in a CO(2) manipulation protocol and/or an LBNP protocol.
      In the CO(2) manipulation protocol, subjects breathed room air (normocapnia) or
      6% inspired CO(2) (hypercapnia), or they hyperventilated to approximately 25 mm
      Hg P(ET)CO(2) (hypocapnia). In the LBNP protocol, subjects experienced 10 minutes
      each of -20 and -40 mm Hg lower body suction. CFV and diameter of the MCA were
      measured by transcranial Doppler and MRI, respectively, during the experimental
      protocols. RESULTS: Compared with normocapnia, hypercapnia produced increases in
      both P(ET)CO(2) (from 36+/-3 to 40+/-4 mm Hg, P<0.05) and CFV (from 63+/-4 to
      80+/-6 cm/s, P<0.001) but did not change MCA diameters (from 2.9+/-0.3 to 2.8+/
      0.3 mm). Hypocapnia produced decreases in both P(ET)CO(2) (24+/-2 mm Hg, P<0.005)
      and CFV (43+/-7 cm/s, P<0.001) compared with normocapnia, with no change in MCA
      diameters (from 2.9+/-0.3 to 2.9+/-0.4 mm). During -40 mm Hg LBNP, P(ET)CO(2) was
      not changed, but CFV (55+/-4 cm/s) was reduced from baseline (58+/-4 cm/s,
      P<0.05), with no change in MCA diameter. CONCLUSIONS: Under the conditions of
      this study, changes in MCA diameter were not detected. Therefore, we conclude
      that relative changes in CFV were representative of changes in CBF during the
      physiological stimuli of moderate LBNP or changes in P(ET)CO(2).

PMID- 10884473
TI  - Delayed treatment with nicotinamide (Vitamin B(3)) improves neurological outcome
      and reduces infarct volume after transient focal cerebral ischemia in Wistar
      rats.
AB  - BACKGROUND AND PURPOSE: We have previously shown that nicotinamide (NAm) acutely
      reduces brain infarction induced by permanent middle cerebral artery occlusion
      (MCAo) in rats. In this study, we investigate whether NAm may protect against
      ischemia/reperfusion injury by improving sensory and motor behavior as well as
      brain infarction volumes in a model of transient focal cerebral ischemia.
      METHODS: Forty-eight male Wistar rats were used, and transient focal cerebral
      ischemia was induced by MCAo for 2 hours, followed by reperfusion for either 3 or
      7 days. Animals were treated with either intraperitoneal saline or NAm (500
      mg/kg) 2 hours after the onset of MCAo (ie, on reperfusion). Sensory and motor
      behavior scores and body weight were obtained daily, and brain infarction volumes
      were measured on euthanasia. RESULTS: Relative to treatment with saline,
      treatment with NAm (500 mg/kg IP) 2 hours after the onset of transient focal
      cerebral ischemia in Wistar rats significantly improved sensory (38%, P<0.005)
      and motor (42%, P<0.05) neurological behavior and weight gain (7%, P<0.05) up to
      7 days after MCAo. The cerebral infarct volumes were also reduced 46% (P<0.05) at
      3 days and 35% (P=0.09) at 7 days after MCAo. CONCLUSIONS: NAm is a robust
      neuroprotective agent against ischemia/reperfusion-induced brain injury in rats,
      even when administered up to 2 hours after the onset of stroke. Delayed NAm
      treatment improved both anatomic and functional indices of brain damage. Further
      studies are needed to clarify whether multiple doses of NAm will improve the
      extent and duration of this neuroprotective effect and to determine the
      mechanism(s) of action underlying the neuroprotection observed. Because NAm is
      already used clinically in large doses and has few side effects, these results
      are encouraging for the further examination of the possible use of NAm as a
      therapeutic neuroprotective agent in the clinical treatment of acute ischemic
      stroke.

PMID- 10884474
TI  - Proteasome inhibitor PS519 reduces infarction and attenuates leukocyte
      infiltration in a rat model of focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Reperfusion brain injury after cerebral ischemia is
      associated with a developing inflammatory response at the site of infarction.
      Proteasome inhibitors block nuclear factor-kappaB activation and provide anti
      inflammatory effects in several animal models of peripheral inflammation. We
      tested the novel proteasome inhibitor PS519 in a rat model of transient focal
      ischemia to establish its pharmacodynamics as a neuroprotection treatment and
      related effects on leukocyte infiltration. METHODS: Rats were subjected to 2
      hours of focal cerebral ischemia by means of the filament method of middle
      cerebral artery occlusion (MCAo). After either 22 or 70 hours of reperfusion,
      infarct size was measured and neurological function, electroencephalographic
      (EEG) activity, and/or neutrophil and macrophage infiltration was quantified.
      PS519 was administered in a single intravenous bolus at 2 hours after MCAo. In
      addition, the therapeutic window for PS519 was estimated by delaying treatment
      for 4 or 6 hours after MCAo. RESULTS: Dose-response analysis of infarct volume at
      24 hours revealed that PS519 neuroprotection approached 60%, and clinical
      evaluations showed significant improvements in neurological function and EEG
      activity. Neutrophil infiltration at 24 hours was also significantly decreased in
      cortical and striatal infarcted tissue of PS519-treated rats. Delaying the PS519
      treatment up to 4 hours continued to result in significant neuroprotection. In
      the 72-hour injury model, infarction was reduced 40% by PS519, and significant
      improvements in neurological function and EEG recovery were again measured.
      Considerable reductions in both neutrophil and macrophage infiltration were
      evident. CONCLUSIONS: PS519 mitigates infarction and improves neurological
      recovery in brain-injured rats, an effect in part caused by a reduction in the
      leukocyte inflammatory response.

PMID- 10884475
TI  - Hypertonic saline worsens infarct volume after transient focal ischemia in rats.
AB  - BACKGROUND AND PURPOSE: Hypertonic saline (HS) has been advocated as a
      hyperosmolar agent for the treatment of cerebral edema, especially after
      traumatic brain injury. We tested the hypothesis that continuous intravenous HS
      administered during reperfusion from transient focal cerebral ischemia attenuates
      infarct volume. METHODS: Halothane-anesthetized male Wistar rats were subjected
      to 2 hours of middle cerebral artery occlusion (MCAO) by the intraluminal
      occlusion technique. At the onset of reperfusion, rats received a 10-mL/kg
      intravenous bolus of 0.9% saline (SAL, n=8) or 7.5% SAL (chloride:acetate 50:50,
      n=8) followed by a continuous infusion for 22 hours. In a second series of
      experiments, ischemic damage was determined in cohorts treated with
      equivolumetric 3% saline (n=8) or 20% mannitol (n=8). In a third series, regional
      cerebral blood flow was measured ([(14)C]iodoantipyrine autoradiography) at 6
      hours of reperfusion in 7.5%-SAL-treated (n=5) or SAL-treated (n=5) animals.
      RESULTS: In SAL rats, serum Na(+) was 137+/-3 and 138+/-2 mEq/L (mean+/-SEM) at
      baseline and 22 hours of reperfusion, respectively. In 7.5% SAL, serum Na(+) was
      136+/-2 and 154+/-2 mEq/L at baseline and reperfusion, respectively.
      Physiological variables and reduction in laser-Doppler signal during MCAO and
      early reperfusion were not different between the 2 treatment groups. Cortical
      infarct volume was larger in 7.5%-SAL-treated rats (121+/-14 mm(3); 30+/-3% of
      contralateral cortex; P<0.05) than in SAL (64+/-15 mm(3); 16+/-4% of
      contralateral cortex). Striatal infarct volume was unchanged by HS therapy.
      Ipsilateral cortical tissue volume was increased relative to the contralateral
      side (by 26+/-5% with SAL; by 41+/-5% with 7.5% SAL). In contrast, ischemic
      damage was unaffected by 3%-SAL or 20%-mannitol treatment compared with SAL.
      Regional cerebral blood flow during reperfusion was heterogeneous in all animals,
      but there was no evidence of postischemic hypoperfusion or blood flow
      maldistribution in 7.5%-SAL-treated animals. CONCLUSIONS: These data demonstrate
      that hypernatremia resulting from postischemic HS infusion worsens cortical
      infarct volume in transient focal cerebral ischemia. The deleterious effect is
      not linked to exacerbation of delayed hypoperfusion during early reperfusion (6
      hours); however, blood flow defects at later recovery time points remain to be
      excluded. These results may have implications for HS therapy in clinical ischemic
      stroke.

PMID- 10884476
TI  - Effects of fluid management on edema volume and midline shift in a rat model of
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effects
      of fluid management on brain water content (BW) and midline shift (MLS) after a
      focal cerebral ischemic insult. METHODS: A suture model was used to induce focal
      cerebral ischemia for 90 minutes (n=44). The rats were randomly assigned to 3
      groups 2. 5 hours after reperfusion: dehydration (n=24), control (n=8), or
      hydration (n=12). BW was obtained with the wet-dry weight method 24 hours after
      middle cerebral artery (MCA) occlusion. In addition, MRI were obtained (n=31) 24
      hours after the onset of ischemia so that the ratio of hemispheric volumes
      ipsilateral (IH) and contralateral (CH) to the infarct and the extent of MLS
      could be obtained. RESULTS: Across the range from moderate dehydration to
      intravascular volume expansion with isotonic saline, BW of the IH increased
      linearly as a function of change in body weight (r(2)=0.89), whereas few changes
      in relation to body weight were observed in CH, indicating a preferential effect
      of fluid management on the infarcted hemisphere. Furthermore, the hemispheric
      volume ratio (IH/CH) and MLS also increased in relation to changes in body
      weight. However, paradoxical increases in BW, IH/CH, and extent of MLS were
      observed in comparison with controls when severe dehydration was produced with
      high-dose mannitol. CONCLUSIONS: Changes in ischemic BW by fluid management
      correlated closely with changes in body weight except when high-dose mannitol was
      used. Mannitol, as a dehydrating agent, may be associated with bimodal effects,
      with a high dose aggravating ischemic BW.

PMID- 10884477
TI  - The N-methyl-D-aspartate antagonist CNS 1102 protects cerebral gray and white
      matter from ischemic injury following temporary focal ischemia in rats.
AB  - BACKGROUND AND PURPOSE: Cerebral white matter is as sensitive as gray matter to
      ischemic injury and is probably amenable to pharmacological intervention. In this
      study we investigated whether an N-methyl-D-aspartate (NMDA) antagonist, CNS
      1102, protects not only cerebral gray matter but also white matter from ischemic
      injury. METHODS: Ten rats underwent 15 minutes of temporary focal ischemia and
      were blindly assigned to CNS 1102 intravenous bolus injection (1. 13 mg/kg)
      followed by intravenous infusion (0.33 mg/kg per hour) for 3.75 hours or to
      vehicle (n=5 per group) immediately after reperfusion. Seventy-two hours after
      ischemia, the animals were perfusion fixed for histology. The severity of
      neuronal necrosis in the cortex and striatum was semiquantitatively analyzed. The
      Luxol fast blue-periodic acid Schiff stain and Bielschowsky's silver stain were
      used to measure optical densities (ODs) of myelin and axons, respectively, in the
      internal capsule of both hemispheres, and the OD ratio was calculated to reflect
      the severity of white matter damage. RESULTS: Neuronal damage in both the cortex
      and the striatum was significantly better in the drug-treated group than in the
      placebo group (P<0.05). The OD ratio of both the axons (0.93+/-0.08 versus 0.61+/
      0.18; P<0.01) and the myelin sheath (0.95+/-0.07 versus 0.67+/-0.19; P=0.01) was
      significantly higher in the CNS 1102 group than in the placebo group. The
      neurological score was significantly improved in the drug-treated group (P<0.05).
      CONCLUSIONS: The NMDA receptor antagonist CNS 1102 protects not only cerebral
      gray matter but also white matter from ischemic injury, most probably by
      preventing degeneration of white matter structures such as myelin and axons.

PMID- 10884478
TI  - Lack of interleukin-6 expression is not protective against focal central nervous
      system ischemia.
AB  - BACKGROUND AND PURPOSE: Interleukin-6 (IL-6) appears to be involved in the
      inflammatory response associated with central nervous system (CNS) ischemia.
      Although IL-6 levels increase after stroke, it is not known whether IL-6 directly
      influences CNS ischemic injury. In this study, we used a focal reversible stroke
      model to investigate whether mice lacking IL-6 were protected against acute
      ischemic injury. METHODS: We bred IL-6-deficient C57 black mice (I-129 IL-6 KO
      back-crossed with C57), including homozygous knockouts (IL-6 -/-), heterozygous
      littermates (IL-6 +/-), and normal littermates (IL-6 +/+). The status of all
      animals was confirmed by DNA sampling and polymerase chain reaction analysis.
      Reversible middle cerebral artery occlusion was produced by advancing a silicone
      coated 8-0 filament into the internal carotid artery for 2 hours (experiment 1)
      or 45 minutes (experiment 2). At 24 hours, animals were evaluated on a 28-point
      clinical scale, blood and cerebrospinal fluid were obtained, and the brains were
      evaluated for infarct volume and IL-6 mRNA levels. RESULTS: In experiment 1
      (severe ischemia), no differences were seen in lesion size or neurological
      function between the groups: lesion volume was IL-6 -/- (n=15), 57+/-13 mm(3); IL
      6 +/- (n=15), 58+/-23 mm(3); and IL-6 +/+ (n=15), 58+/-18 mm(3) (P=NS). ELISA
      testing confirmed very low to absent levels of IL-6 in the serum and
      cerebrospinal fluid of knockout animals. Brain mRNA levels of the other
      proinflammatory cytokines, including tumor necrosis factor-alpha, IL-1beta, and
      IL-1 receptor antagonist, were 50% lower in IL-6-deficient ischemic animals than
      in normal animals. In experiment 2 (mild ischemia), no differences were seen in
      lesion size or neurological function between the groups: lesion volume was IL-6 
      /- (n=10), 16+/-8 mm(3); IL-6 +/- (n=10), 14+/-4 mm(3); and IL-6 +/+ (n=10), 19+/
      12 mm(3) (P=NS). CONCLUSIONS: In this study, infarct size and neurological
      function at 24 hours were not different in animals deficient in IL-6 after
      transient CNS ischemia. This suggests that IL-6 does not have a direct influence
      on acute ischemic injury. Further study investigating the role of IL-6 on long
      term recovery after stroke is in progress.

PMID- 10884479
TI  - Intracortical hemorrhage injury in rats : relationship between blood fractions
      and brain cell death.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage is associated with stroke and
      head trauma. The purposes of this study were to investigate the effect of
      intracortical injections of autologous whole blood and blood components on
      inflammatory cell infiltration and brain cell death and to determine if
      nonhemorrhagic lesions differ in these respects. METHODS: Eighty-seven adult rats
      were subjected to intracortical injections of autologous whole blood or
      allogeneic plasma, erythrocytes, leukocytes, "activated" leukocytes, and serum.
      Injections of saline or mineral oil were controls. Blood injections were compared
      with cortical freeze injury and pial devascularization. Rats were perfusion-fixed
      48 hours after injection or lesioning. Eosinophilic neurons, TUNEL-positive
      cells, brain damage area, infiltrating neutrophils, and CD8a-immunoreactive
      lymphocytes were quantified. RESULTS: Damage area, dying cells, and inflammatory
      infiltrate were significantly greater after autologous whole blood, leukocyte,
      and "activated" leukocyte injections than injection of other fractions.
      CONCLUSIONS: These results suggest that extravasated whole blood causes a greater
      degree of cortical cell death and inflammation than ischemic lesions of similar
      size. Leukocytes "activated" by systemic illness might exacerbate the injury.
      Secondary hemorrhagic phenomena suggest that the harmful effect is directed
      toward both brain cells and the vasculature. Further studies are required to
      delineate the mechanism(s).

PMID- 10884480
TI  - Visualization of brain perfusion with harmonic gray scale and power doppler
      technology : an animal pilot study.
AB  - BACKGROUND AND PURPOSE: It is unclear which harmonic imaging mode (power Doppler
      or gray-scale imaging) is superior and which measuring method is the most robust
      for the description of brain perfusion. METHODS: We performed an animal study on
      6 beagles through the intact skull using a SONOS 5500 device and Optison injected
      intravenously in 3 different doses (0.15, 0.3, and 0.6 mL). Intensity versus
      heart-cycle plots for the brain parenchyma and the basal cerebral arteries were
      generated to evaluate the peak increase (PI) from baseline and the area under the
      curve (AUC). RESULTS: With harmonic gray-scale imaging, a homogeneous increase in
      echo contrast of the brain parenchyma was observed. The effect was dose
      dependent, resulting in a significant increase in PI as well as an insignificant
      increase of the AUC with 0.3 mL versus 0.15 mL contrast agent (P=0.03 and P=0.65,
      respectively; n=5). With harmonic power Doppler, injection of the 3 different
      doses resulted in a nonsignificant increase in PI and AUC P=0.17, n=6 for both).
      After normalization of the brain signal to the peak arterial signal in individual
      dogs, a significant increase could be demonstrated (P=0. 03 and P=0.01,
      respectively; n=6). The signal pattern of harmonic power Doppler was
      inhomogeneous, with stronger signal increases in the anterior part of the brain.
      CONCLUSIONS: Gray-scale imaging leads to a more homogeneous increase in echo
      contrast of the brain tissue and may be more suitable for displaying brain
      perfusion. The PI of the signal intensity seems the most robust parameter for the
      description of cerebral perfusion with both imaging modes under investigation.

PMID- 10884481
TI  - Contribution of microglia/macrophages to expansion of infarction and response of
      oligodendrocytes after focal cerebral ischemia in rats.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was (1) to examine the
      contribution of microglia and macrophages with their interleukin-1beta production
      and (2) to assess the vulnerability and response of oligodendrocytes in cerebral
      infarction. METHODS: Male Wistar rats were subjected to permanent occlusion of
      the left middle cerebral artery. Expansion of ischemic infarction and response of
      oligodendrocytes were investigated together with accumulation of inflammatory
      cells, production of interleukin-1beta, and disruption of the blood-brain
      barrier. Apoptotic cell death was inferred from fragmented DNA and the expression
      of proapoptotic Bax protein. RESULTS: During expansion of infarction, amoeboid
      microglia and extravasation of serum albumin were observed not only in the
      infarcted area but also in the adjacent surviving area, whereas macrophages
      accumulated along the boundary and granulocytes migrated into the center of the
      infarction. Both amoeboid microglia and macrophages produced interleukin-1beta,
      an inflammatory cytokine, during an early ischemic period. Furthermore,
      macrophages within the infarcted tissue expressed Bax protein and subsequently
      showed fragmented nuclear DNA. Oligodendrocytes were detected in the infarcted
      area even after 24 hours following middle cerebral artery occlusion, but they
      subsequently developed fragmented DNA. A week after onset of ischemia,
      oligodendrocytes were found to be accumulated in the intact area bordered with
      the infarct together with reactive astrocytes. CONCLUSIONS: Our results suggest
      the importance of amoeboid microglia, macrophages, and their interleukin-1beta
      production in gradual expansion of cerebral infarction. Resident oligodendrocytes
      may be resistant to ischemic insults, and oligodendrocytes accumulated at the
      border of the infarction may participate in tissue repair after cerebral
      infarction.

PMID- 10884482
TI  - Oxygen-glucose deprivation induces inducible nitric oxide synthase and
      nitrotyrosine expression in cerebral endothelial cells.
AB  - BACKGROUND AND PURPOSE: The cerebral endothelial cells (ECs) are a primary target
      of hypoxic or ischemic brain insults. EC damage may contribute to postischemic
      secondary injury. Massive production of NO after inducible NO synthase (iNOS)
      expression has been implicated in cell death. This study aimed to characterize
      bovine cerebral EC death in relation to iNOS expression after oxygen-glucose
      deprivation (OGD) in vitro. METHODS: OGD in bovine cerebral ECs in culture was
      induced by deleting glucose in the medium and by incubating the cells in a
      temperature-controlled anaerobic chamber. The extent of cell death was assessed
      by trypan blue exclusion, MTT assay, and LDH release. ELISA, gel electrophoresis,
      and staining by terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling were used to examine DNA fragmentation. The expression of iNOS mRNA and
      protein was detected by reverse transcription-polymerase chain reaction and
      Western blotting, respectively. Nitrotyrosine expression was confirmed with
      Western blot analysis and immunostaining. RESULTS: Bovine cerebral EC death was
      dependent on the duration of OGD and showed selected biochemical, morphological,
      and pharmacological features suggestive of apoptosis. OGD also induced the
      expression of iNOS mRNA and protein in bovine cerebral ECs. Increased expression
      of nitrotyrosine, the product formed by peroxynitrite reaction with proteins, was
      also detected after OGD. The involvement of iNOS in EC death was suggested by
      partial reduction of cell death by NO synthase inhibitors, including L-N(G)-(1
      iminoethyl)ornithine and nitro-L-arginine, and an NO scavenger, the Fe(2+)-N
      methyl-D-glucamine dithiocarbamate complex. CONCLUSIONS: OGD-induced bovine
      cerebral EC death involves an apoptotic process. Induction of iNOS with
      subsequent peroxynitrite formation may contribute to bovine cerebral EC death
      caused by OGD.

PMID- 10884483
TI  - Evolution of brain injury after transient middle cerebral artery occlusion in
      neonatal rats.
AB  - BACKGROUND AND PURPOSE: Stroke in preterm and term babies is common and results
      in significant morbidity. The vulnerability and pathophysiological mechanisms of
      neonatal cerebral ischemia-reperfusion may differ from those in the mature
      cerebral nervous system because of the immaturity of many receptor systems and
      differences in metabolism in neonatal brain. This study details the
      neuropathological sequelae of reperfusion-induced brain injury after transient
      middle cerebral artery (MCA) occlusion in the postnatal day 7 (P7) rat. METHODS:
      P7 rats were subjected to 3 hours of MCA occlusion followed by reperfusion or
      sham surgery. Diffusion-weighted MRI was performed during MCA occlusion, and maps
      of the apparent diffusion coefficient (ADC) were constructed. Contrast-enhanced
      MRI was performed in a subset of animals before and 20 minutes after reperfusion.
      Triphenyltetrazolium chloride (TTC) staining of the brain was performed 24 hours
      after reperfusion. Immunohistochemistry to identify astrocytes (glial fibrillary
      acidic protein), reactive microglia (ED-1), and neurons (microtubule-associated
      protein 2) and cresyl violet staining were done 4, 8, 24, and 72 hours after
      reperfusion. RESULTS: On contrast-enhanced MRI, nearly complete disruption of
      cerebral blood flow was evident in the vascular territory of the MCA during
      occlusion. Partial restoration of blood flow occurred after removal of the
      suture. A significant decrease of the ADC, indicative of early cytotoxic edema,
      occurred in anatomic regions with a disrupted blood supply. The decline in ADC
      was associated with TTC- and cresyl violet-determined brain injury in these
      regions 24 hours later. The ischemic core was rapidly infiltrated with reactive
      microglia and was surrounded by reactive astroglia. CONCLUSIONS: In P7 rats,
      transient MCA occlusion causes acute cytotoxic edema and severe unilateral brain
      injury. The presence of a prominent inflammatory response suggests that both the
      ischemic episode and the reperfusion contribute to the neuropathological outcome.

PMID- 10884484
TI  - Loss of psychic self-activation after paramedian bithalamic infarction.
AB  - BACKGROUND AND PURPOSE: Loss of psychic self-activation has been described after
      bilateral lesions to the globus pallidus, striatum, and white matter of the
      frontal lobes, but it is a very rare sign of bithalamic lesions. The exact
      functional-anatomic mechanism underlying loss of psychic self-activation
      following bithalamic lesions remains to be elucidated. CASE DESCRIPTION: We
      present clinical, neuropsychological, structural, and functional neuroimaging
      data of an 18-month follow-up period of a man with prominent loss of psychic self
      activation after coronary arteriography. Except for memory decline, accompanying
      symptoms remained restricted to the acute phase. The neurobehavioral syndrome
      consisted mainly of apathy, indifference, poor motivation, and flattened affect,
      and this remained unchanged during the entire follow-up period. MRI showed a
      bithalamic infarction involving the nucleus medialis thalami bilaterally. Single
      photon emission CT revealed a severe relative hypoperfusion of both thalami, a
      relative hypoperfusion of both nuclei caudati, and a relative hypoperfusion
      mesiofrontally. CONCLUSIONS: Single-photon emission CT data support the
      hypothesis that the neurobehavioral manifestations after bithalamic paramedian
      infarction are caused by disruption of the striatal-ventral pallidal-thalamic
      frontomesial limbic loop. Probably, bilateral disruption at different levels of
      the striatal-ventral pallidal-thalamic-frontomesial loop may lead to a similar
      clinical picture consisting of loss of psychic self-activation.

PMID- 10884485
TI  - Facial palsy in cerebral venous thrombosis : transcranial stimulation and
      pathophysiological considerations.
AB  - BACKGROUND: Cranial nerve palsy in cerebral sinovenous thrombosis (CVT) is rare,
      its pathophysiology remains unclear, and data from electrophysiological
      examinations in such patients are missing. CASE DESCRIPTION: We report the case
      of a 17-year-old woman with familial protein S deficiency who was admitted with
      extensive multiple CVT. Two weeks after onset of symptoms, she developed isolated
      right peripheral facial palsy, and MR venography showed segmental occlusion of
      the ipsilateral transverse sinus. Complete recovery of facial palsy occurred
      concomitant with recanalization of the transverse sinus. Facial neurography,
      including transcranial magnetic stimulation of the facial nerve and related motor
      cortex, ruled out a coincidental idiopathic palsy and revealed conduction block
      proximal to the facial canal. CONCLUSIONS: Facial palsy in our patient was caused
      by transient neurapraxia in the intracranial segment of the nerve. We suggest
      that elevated venous transmural pressure in the nerve's satellite vein, which
      belongs to the affected drainage territory of the transverse sinus, might have
      caused venous blood-brain barrier dysfunction in the intrinsic vascular system of
      the nerve, with leakage of fluids and ions into the endoneurial space and thus an
      increase in interstitial resistance.

PMID- 10884486
TI  - Low-molecular-weight heparins and heparinoids in acute ischemic stroke : a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND AND PURPOSE: Low-molecular-weight heparins and heparinoids (LMWHs) are
      superior to unfractionated heparin in the prevention and treatment of venous
      thromboembolism and acute coronary syndromes. We performed a systematic review of
      randomized controlled trials (RCTs) to examine the safety and efficacy of LMWH in
      acute ischemic stroke. METHODS: Randomized, controlled, and nonconfounded trials
      of LMWH in acute ischemic stroke were identified from the Cochrane Library
      (version 2, 1999), previous systematic reviews, and a review of publication
      quality relating to acute stroke trials. The authors each independently extracted
      data by treatment group and assessed trial quality using Cochrane Collaboration
      criteria. RESULTS: Eleven completed RCTs involving 3048 patients were identified;
      data were available from 10 of these. Four trials explicitly excluded patients
      with presumed cardioembolic stroke. Treatment with LMWH was associated with
      significant reductions in prospectively identified deep vein thrombosis (OR 0.27,
      95% CI 0.08 to 0.96) and symptomatic pulmonary embolism (OR 0.34, 95% CI 0.17 to
      0.69) and with increased major extracranial hemorrhage (OR 2.17, 95% 1.10 to
      4.28). Nonsignificant increases in end-of-treatment (OR 1.20, 95% CI 0.86 to
      1.69) and end-of-trial (OR 1.05, 95% CI 0.83 to 1.32) case fatality and
      symptomatic intracranial hemorrhage (OR 1.77, 95% CI 0. 95 to 3.31) were
      observed. End-of-trial death and disability was nonsignificantly reduced (OR
      0.87, 95% CI 0.72 to 1.06). CONCLUSIONS: ++LMWHs reduce venous thromboembolic
      events in patients with acute ischemic stroke and increase the risk of
      extracranial bleeding. A nonsignificant reduction in combined death and
      disability and nonsignificant increases in case fatality and symptomatic
      intracranial hemorrhage were also observed. On the basis of the current evidence,
      LMWH should not be used in the routine management of patients with ischemic
      stroke.

PMID- 10884487
TI  - Thienopyridines or aspirin to prevent stroke and other serious vascular events in
      patients at high risk of vascular disease? A systematic review of the evidence
      from randomized trials.
AB  - BACKGROUND AND PURPOSE: Aspirin is the most widely studied and prescribed
      antiplatelet drug for patients at high risk of vascular disease. We aimed to
      establish how the thienopyridines (ticlopidine and clopidogrel) compare with
      aspirin in terms of effectiveness and safety. METHODS: We did a systematic review
      of all unconfounded randomized trials comparing either ticlopidine or clopidogrel
      with aspirin for patients at high risk of vascular disease. The primary outcome
      was vascular events (stroke, myocardial infarction, or vascular death). Adverse
      outcomes were intracranial and extracranial hemorrhage, upper and lower
      gastrointestinal disturbances, neutropenia, thrombocytopenia, and skin rash.
      RESULTS: In 4 trials among 22 656 patients (including 9840 presenting with a
      transient ischemic attack/ischemic stroke), the thienopyridines reduced the odds
      of a vascular event by 9% (odds ratio 0.91, 95% CI 0.84 to 0. 98; 2P=0.01),
      preventing 11 (95% CI 2 to 19) events per 1000 patients treated for approximately
      2 years. The thienopyridines produced significantly less gastrointestinal
      hemorrhage and upper gastrointestinal upset (indigestion/nausea/vomiting) than
      did aspirin. Both thienopyridines increased the odds of skin rash and of diarrhea
      (ticlopidine by approximately 2-fold and clopidogrel by approximately one third).
      Only ticlopidine increased the odds of neutropenia. CONCLUSIONS: The
      thienopyridines appear modestly more effective than aspirin in preventing serious
      vascular events in high-risk patients. Clopidogrel appears to be safer than
      ticlopidine and as safe as aspirin, making it an appropriate, but more expensive,
      alternative antiplatelet drug for patients unable to tolerate aspirin. However,
      there is insufficient information to determine which particular types of patients
      would benefit most, and which least, from clopidogrel instead of aspirin.

PMID- 10884488
TI  - Clinical relevance of detecting asymptomatic embolic signals in acute stroke.

PMID- 10884489
TI  - Reduced ICA diameter and reduced stroke risk.

PMID- 10884490
TI  - G20210A PRTH gene mutation and other trombophilic polymorphisms in patients with
      cerebral vein thrombosis.

PMID- 10884491
TI  - No side effects after low-dose amphetamine administration in stroke
      rehabilitation.

PMID- 10884492
TI  - Transfemoral digital subtraction angiography for assessment of vertebral artery
      occlusion in rats.

PMID- 10884493
TI  - Extraparenchymal bleeding predicts an unfavorable outcome in patients with
      hemorrhagic transformation.

PMID- 10884494
TI  - Abstracts of Literature.

PMID- 10884495
TI  - Clinical trials in childhood cancers.

PMID- 10884496
TI  - Primary mediastinal malignancies in children: report of 22 patients and
      comparison to 197 adults.
AB  - PURPOSE: Examine a contemporary series of patients with primary pediatric
      malignant mediastinal tumors and determine epidemiology, histology, treatment,
      and survival. Patients and Methods. All malignancies diagnosed between January 1,
      1973 and December 31, 1995 were analyzed. RESULTS: Twenty-two patients, age 18
      years or less, with pediatric primary mediastinal malignancies were identified
      from a database of 110,284 patients with primary malignancies. During the same
      period, 197 adult patients with primary mediastinal malignancies were identified.
      Fifty-nine percent of the pediatric patients were male. Median age was 11 years.
      Lymphoma was present in 55%, neurogenic malignancies in 23%, malignant germ cell
      tumors in 18%, and sarcoma in 5%. Neurogenic tumors presented in infants and
      lymphomas and germ cell tumors presented in teens (p = 0.005). In treated
      children, surgery was used more often in neurogenic tumors and germ cell tumors
      than in lymphomas (p = 0.002). Five-year survival was 74% for lymphomas, 67% for
      neurogenic tumors, 25% for germ cell tumors, and 61% overall (p = 0.23). Compared
      to adults, children had more neurogenic tumors (p < 0.001) and fewer thymomas (p
      = 0.0499). There were no significant differences in staging or survival between
      children and adults. CONCLUSIONS: Pediatric mediastinal malignancies occurred
      with a frequency of 1/5,013 patients with malignant tumors. Lymphoma, neurogenic
      tumors, and germ cell tumors predominated. Compared to adults, children had more
      neurogenic tumors and fewer thymomas. Within the pediatric group, differences
      were found in age of presentation between histologic groups. These differences
      between adults and children, and between infants and teens, should be considered
      when evaluating a patient suspected of having mediastinal malignancy.

PMID- 10884497
TI  - Anti-cancer drug discovery and development in Brazil: targeted plant collection
      as a rational strategy to acquire candidate anti-cancer compounds.
AB  - Throughout medical history, plant products have been shown to be valuable sources
      of novel anti-cancer drugs. Examples are the VINCA: alkaloids, the taxanes, and
      the camptothecins, derived from the Madagscan periwinkle plant Catharantus
      roseus, the Pacific yew Taxus brevifolia, and the Chinese tree Camptotheca
      acuminata, respectively. For this reason, the South-American Office for Anti
      Cancer Drug Development has implemented a large-scale project of acquisition and
      testing of compounds isolated from South American medicinal plants. The species
      are selected on the basis of a potentially useful phytochemical composition by
      consulting ethnopharmacological, chemosystemic, and ecological information. The
      collected samples are dried and first extracted with an organic solvent, then
      with distilled water. These crude extracts are evaluated at a concentration of 50
      microg/ml for antiproliferative activity against one cell line. Extracts that
      significantly inhibit the growth of the cells (>/=50%) at relatively low
      concentrations (</=50 microg/ml) are submitted to the more comprehensive disease
      oriented screen of the U.S. National Cancer Institute. In parallel, these samples
      are further purified by bioassay-guided purification, involving repeated
      fractionation by diverse chromatography methods. If the active substance is
      expected to represent a novel structure, it is identified by appropriate chemical
      techniques, mechanistic studies are performed with a wide diversity of tumor
      models and laboratory techniques, and efforts are undertaken for the synthesis of
      potentially more useful analogs.

PMID- 10884498
TI  - Role of taxoids in head and neck cancer.
AB  - Docetaxel and paclitaxel represent a new class of cytotoxic agents having both a
      specific chemical structure and mechanism of action. They act to promote tubulin
      polymerization and the formation of stable microtubules. The microtubules
      produced in the presence of taxoids are resistant to disassembly by physiologic
      stimuli, and cells exposed to these agents exhibit an accumulation of
      disorganized microtubule arrays. This affects the normal mitotic process and
      eventually results in cell death. Both drugs are active as single agents in
      patients with head and neck cancer with response rates ranging from 20% to 40%.
      They may be combined with other cytotoxic agents, radiotherapy, or both. A review
      is given of the presently available data.

PMID- 10884499
TI  - High-dose rate brachytherapy of bronchial cancer: treatment optimization using
      three schemes of therapy.
AB  - PURPOSE: Our aim is to demonstrate that a fractionated high-dose rate
      endobronchial brachytherapy (HDRBT) treatment is tolerable for patients with
      advanced (IIIA-IIIB) non-small cell lung cancer and gives an improvement of
      symptoms. Patients and Methods. From January 1992 to July 1997, we treated 320
      patients with external beam radiotherapy (EBRT) and concomitant HDRBT with Ir192.
      Eighty-four patients received 10 Gy in one fraction from January 1992 to March
      1993 (Group A); 47 patients received two fractions of 7 Gy each from April 1993
      to December 1993 (Group B), and 189 patients received three fractions of 5 Gy
      each from January 1994 to July 1997 (Group C). RESULTS: Mean survival from
      diagnosis is 11.1 months and mean survival from last HDRBT is 9.7 months. The
      symptomatic response rate is 90% for dyspnea, 82% for cough, 94% for hemoptysis
      and 90% for obstructive pneumonia. Performance status was improved in 70% of
      patients. Follow-up is in the range of 5-36 months with 280/320 evaluable
      patients (87.5%) (40 patients were lost to follow-up). For the patients treated
      with three fractions of HDRBT plus EBRT, a smaller number of side effects
      occurred while relief from symptoms linked to bronchial obstruction and survival
      was similar for the three groups. CONCLUSIONS: A three-fraction brachytherapy
      results in fewer side effects, such as bronchial fibrosis with or without
      stenosis, while survival and symptomatic relief are similar in the three groups
      treated.

PMID- 10884500
TI  - Nonmyeloablative allogeneic stem cell transplant strategies and the role of mixed
      chimerism.
AB  - Experimental and clinical experiences have demonstrated successsful donor
      engraftment following nonmyeloablative preparative regimens. These less toxic
      conditioning strategies may be better tolerated with diminished transplant
      related morbidity and mortality. Importantly, the intentional induction of mixed
      chimerism can be established following nonmyeloablative conditioning. This
      approach has the potential advantages of inhibiting graft-versus-host disease,
      presumably secondary to the persistence of host immunoregulatory cells, and
      providing a platform for the delivery of adoptive cellular immunotherapy with
      donor leukocyte infusions for patients with an underlying malignancy. This review
      will describe the preclinical evolution of nonmyeloablative transplant
      strategies, the rationale for considering these approaches, and the preliminary
      clinical experience with this novel allogeneic stem cell therapy.

PMID- 10884501
TI  - Management of cancer in the older person: a practical approach.
AB  - The management of cancer in the older aged person is an increasingly common
      problem. The questions arising from this problem are: Is the patient going to die
      with cancer or of cancer? Is the patient able to tolerate the stress of
      antineoplastic therapy? Is the treatment producing more benefits than harm? This
      article explores a practical, albeit evolving, approach to these questions
      including a multidimensional assessment of the older person and simple
      pharmacologic interventions that may ameliorate the toxicity of antineoplastic
      agents. Age may be construed as a progressive loss of stress tolerance, due to
      decline in functional reserve of multiple organ systems, high prevalence of
      comorbid conditions, limited socioeconomic support, reduced cognition, and higher
      prevalence of depression. Aging is highly individualized: chronologic age may not
      reflect the functional reserve and life expectancy of an individual. A
      comprehensive geriatric assessment (CGA) best accounts for the diversities in the
      geriatric population. The advantages of the CGA include:Recognition of
      potentially treatable conditions such as depression or malnutrition, that may
      lessen the tolerance of cancer treatment and be reversed with proper
      intervention; Assessment of individual functional reserve; Gross estimate of
      individual life expectancy; and Adoption of a common language to classify older
      cancer patients. The CGA allows the practitioner to recognize at least three
      stages of aging:People who are functionally independent and without comorbidity,
      who are candidates for any form of standard cancer treatment, with the possible
      exception of bone marrow transplant. People who are frail (dependence in one or
      more activities of daily living, three or more comorbid conditions, one or more
      geriatric syndromes), who are a candidate only for palliative treatment; and
      People in between, who may benefit from some special pharmacological approach,
      such as reduction in the initial dose of chemotherapy with subsequent does
      escalations. The pharmacological changes of age include decreased renal excretion
      of drugs and increased susceptibility to myelosuppression, mucositis,
      cardiotoxicity and neurotoxicity. Based on these findings, the proposal was made
      that all persons aged 70 and older, treated with cytotoxic chemotherapy of dose
      intensity comparable to CHOP, receive prophylactic growth factor treatment, and
      that the hemoglobin of these patients be maintained >/=12 gm/dl.

PMID- 10884502
TI  - The prednisone dosage in the CHOP chemotherapy regimen for non-Hodgkin's
      lymphomas (NHL): is there a standard?
AB  - PURPOSE: Discrepancies in the quoted prednisone dosages in the regimens reported
      as the only standard CHOP regimen stimulated our interest in reviewing the
      medical literature regarding this issue and to assess whether practicing
      hematologists and oncologists in the U.S. are aware of the different dose
      schedules of prednisone in the published CHOP programs. METHODS: Sixteen
      textbooks and chemotherapy reference books were reviewed. A MEDLINE search of
      English-language articles published between January 1970 and December 1998 was
      performed. An eight-point questionnaire was sent via e-mail with responses
      obtained from 421 hematology/oncology physicians in the U.S. RESULTS: Sixteen
      textbooks and chemotherapy reference books reviewed quoted only one prednisone
      dosage as part of the standard CHOP regimen; the prednisone dosages quoted as
      standard varied between publications. More than 4,000 eligible non-Hodgkin's
      lymphoma patients have been treated with the CHOP chemotherapy as part of 43
      different clinical trials reviewed. The dosages of prednisone and prednisolone
      used varied among six different levels. Thirty percent (127/421) of practicing
      U.S. physicians were not aware of the existence of more than one prednisone dose
      schedule as part of the CHOP regimen. The three most frequently used dosages are
      100 mg/days 1-5 (67%), 100 mg/m(2)/days 1-5 (17%), and 60 mg/m(2)/days 1-5 (13%).
      CONCLUSIONS: Discrepancies in steroid dosages used as part of the reported
      standard CHOP regimens are common and not well recognized in the medical
      literature nor by practicing U.S. hematologists/oncologists. Based on this study,
      a prednisone dose of 100 mg/day for five days should be considered the standard
      dose.

PMID- 10884503
TI  - The consequences of diarrhea occurring during chemotherapy for colorectal cancer:
      a retrospective study.
AB  - PURPOSE: Diarrhea is one of the dose-limiting toxicities associated with
      chemotherapy agents in treatment regimens for colorectal cancer. The objectives
      of this study were to analyze the impact of all grades of diarrhea on clinical
      decisions for patients receiving treatment for colorectal cancer by
      characterizing the diarrhea that occurred, quantifying changes in chemotherapy
      treatment, identifying methods to treat diarrhea, and determining the economic
      impact. Patients and Methods. We retrospectively reviewed the treatment of 100
      consecutive patients with colorectal cancer who experienced diarrhea during the
      course of chemotherapy. The diarrhea was documented in the progress notes and
      graded according to National Cancer Institute Common Toxicity Criteria. Changes
      in chemotherapy treatment and resource utilization associated with diarrhea were
      recorded. RESULTS: The 100 patients received 673 chemotherapy cycles, of which
      45% +/- 2% were associated with diarrhea. Approximately 52% of patients
      experienced diarrhea of grades 3 or 4, and 56 patients underwent 66 modifications
      in their chemotherapy treatment, such as dose reductions (22), delays in therapy
      (8), discontinuations of therapy (15), or multiple changes (11). Thirty-seven
      patients consumed resources beyond oral antidiarrheals to control diarrhea: 14
      patients received emergency outpatient treatment, 23 patients were hospitalized,
      21 patients received intravenous fluids, and one death due to dehydration was
      reported. Discussion and Conclusion. Diarrhea was a significant consequence of
      colorectal chemotherapy, with the majority of patients experiencing grades 3 or 4
      diarrhea and 56% of all patients also modifying their chemotherapy treatment.
      Even mild diarrhea of grades 1 and 2 was associated with changes in treatment in
      11% of patients; thus, diarrhea of all grades should be recognized and treated
      appropriately to maintain full-dose chemotherapy.

PMID- 10884504
TI  - The molecular perspective: simian virus 40.

PMID- 10884505
TI  - The role of behavioral and psychosocial science in reducing cancer morbidity and
      mortality.
AB  - Behavioral and psychosocial science has the potential to contribute much to the
      overall effort to reduce cancer morbidity and mortality and to improve the
      quality of life for cancer patients and their families. However, for a variety of
      reasons, including a lack of sustained funding for research and training and a
      lack of confidence by some in the potential payoff for investments in the area,
      this potential has not only not been realized but also not been adequately
      explored. A special subcommittee of "The March" Research Task Force studied
      research in this area and issued a report making several recommendations for
      future funding for psychosocial and behavioral research in cancer. This article
      reports those recommendations and the reasons the committee supported them.

PMID- 10884506
TI  - Eriochrome Black T inhibits endothelial cell growth through S-phase blockade.
AB  - We used human umbilical vein endothelial cells (HUVEC) cultures to investigate in
      vitro the antiproliferative effects of suramin and of its analogue, Eriochrome
      Black T. The cell cycle phases of interest were characterised with specific
      immune sera raised against cyclin D(1), cyclin E and proliferating nuclear cell
      antigen (PCNA). Simultaneous detection of two cell cycle markers was ensured by
      double colour immunofluorescence. Both compounds inhibited the endothelial cell
      growth while Eriochrome Black T was more potent than suramin. Suramin induced
      HUVEC to accumulate in G1-phase as an increase of the number of cells expressing
      both cyclin D(1) and PCNA was observed. Eriochrome Black T preferentially blocked
      them in the early S-phase, as it increased the proportion of cyclin E positive
      cells. These results suggest that in addition of its more potent
      antiproliferative effect on endothelial cell growth, Eriochrome Black T acts at
      another molecular level than suramin.

PMID- 10884507
TI  - Antiplatelet mechanisms of TA-993 and its metabolite MB3 in ADP-induced platelet
      aggregation.
AB  - We investigated the antiplatelet mechanisms of TA-993 [(-)-cis-3-acetoxy-5-(2
      (dimethylamino)ethyl)-2, 3-dihydro-8-methyl-2-(4-methylphenyl)-1,5-benzothiazepin
      4(5H)-one maleate] and its metabolite MB3 (deacetyl and N-monomethyl TA-993) in
      human platelets stimulated by ADP in vitro. TA-993 and MB3 concentration
      dependently inhibited fibrinogen binding to the ADP-stimulated platelets as well
      as inhibiting platelet aggregation. The antiplatelet effect of MB3 was about 300
      times more potent than those of TA-993 and a glycoprotein IIb/IIIa receptor
      antagonist, Arg-Gly-Asp-Ser (RGDS). Aggregation of ADP-treated fixed platelets
      caused by the addition of fibrinogen was inhibited by RGDS but not by TA-993 and
      MB3. TA-993 and MB3 inhibited ADP-induced polymerization of actin filaments.
      Neither TA-993 nor MB3 affected cyclic AMP and cyclic GMP levels in resting
      platelets, and nor suppressed the increase in intracellular Ca(2+) concentration
      induced by ADP. These results suggest that the antiplatelet mechanisms of TA-993
      and MB3 may involve inactivation of glycoprotein IIb/IIIa receptors via
      inhibition of the polymerization of actin.

PMID- 10884508
TI  - Cloning, expression, and characterization of ferret 5-HT(3) receptor subunit.
AB  - Ferrets (Mustela putorius furo) are useful animals for determining anti-emetic
      activity via 5-HT(3) receptors in vivo. We isolated a cDNA encoding the 5
      hydroxytryptamine (5-HT) type 3A receptor subunit (5-HT(3A)) from ferret colon,
      expressed it in a human embryonic kidney cell line and determined its
      pharmacological properties. The open reading frame of the isolated cDNA encoded a
      483-amino acid protein, corresponding to the shorter splice variant of 5-HT(3A)
      receptors. Splice variants were no longer detected by reverse transcriptase
      polymerase chain reaction. The ferret 5-HT(3A) receptor exhibits a high degree of
      amino acid sequence identity (>/=80%) to that of other species. Binding studies
      demonstrated the following rank order of potency for agonists: meta
      chlorophenylbiguanide (mCPBG)>2-methyl-5-hydroxytryptamine (2-Me-5-HT)=5-HT, and
      for antagonists: ondansetron=tropisetron>(+)-tubocurarine>metoclopramide.
      Electrophysiological studies revealed that mCPBG was a partial agonist and 2-Me-5
      HT was an almost fully effective agonist compared to 5-HT.

PMID- 10884509
TI  - Mechanism of suppression of cardiac L-type Ca(2+) currents by the phospholipase
      A(2) inhibitor mepacrine.
AB  - Phospholipase A(2) plays a crucial role in the release of arachidonic acid (AA)
      from membrane phospholipids and in myocardial injury during ischemia and
      reperfusion. Mepacrine, a phospholipase A(2) inhibitor, has been shown to protect
      the heart from ischemic injury. In order to examine the mechanism of this
      protection, we investigated the effects of mepacrine on the L-type Ca(2+) current
      (I(Ca,L)) in rat single ventricular myocytes. Extracellular application of
      mepacrine significantly inhibited I(Ca,L) in a tonic- and use-dependent manner.
      The inhibition was also concentration-dependent with an IC(50) of 5.2 microM.
      Neither the activation nor the steady-state inactivation of I(Ca,L) was altered
      by mepacrine. The mepacrine-induced inhibition of I(Ca,L) was reversible after
      washout of the inhibitor. Addition of 1 microM AA partially reversed the
      mepacrine-induced inhibition of I(Ca,L). Intracellular dialysis, with 2 mM cAMP,
      significantly increased I(Ca, L), but did not prevent the mepacrine-induced
      inhibition of I(Ca,L). In addition, extracellular application of isoproterenol or
      membrane permeable db-cAMP did not reverse the mepacrine-induced inhibition of
      I(Ca,L). Biochemical measurement revealed that incubation of ventricular myocytes
      with mepacrine significantly reduced intracellular cAMP levels. The mepacrine
      induced reduction of cAMP production was abolished by addition of AA. Our results
      demonstrate that mepacrine strongly inhibits cardiac I(Ca,L). While mepacrine is
      a phospholipase A(2) inhibitor and reduces cAMP production, its inhibitory effect
      on I(Ca,L) mainly results from a direct block of the channel. Therefore, we
      speculate that the protective effect of mepacrine during myocardial ischemia and
      reperfusion mostly relates to its blockade of Ca(2+) channels.

PMID- 10884510
TI  - Neuroprotective activity of chemokines against N-methyl-D-aspartate or beta
      amyloid-induced toxicity in culture.
AB  - We have examined the effect of various chemokines on neuronal toxicity in
      culture. In mixed cortical cultures, challenged with a brief pulse of N-methyl-D
      aspartate (NMDA, 60 microM, 10 min), chemokines were either present for 2 h
      preceding the pulse or they were co-applied with NMDA and then kept in the medium
      for the following 20-24 h. Interleukin-8 (IL-8), regulated on activation of
      normal T cells expressed and secreted (RANTES) and macrophage/monocyte
      chemoattractant protein-1 (MCP-1), were neuroprotective under both conditions,
      whereas stromal cell-derived factor 1alpha (SDF-1alpha) was protective only when
      applied during and after the NMDA pulse. Mixed or pure neuronal cultures were
      also exposed for 48 h to a toxic fragment of the beta-amyloid peptide (beta
      amyloid peptide-(25-35), 12.5 or 25 microM) in the absence or presence of
      chemokines. Among a number of chemokines, only RANTES was neuroprotective against
      beta-amyloid peptide-(25-35)-induced neurotoxicity in both cultures. We conclude
      that activation of chemokine receptors differentially affects neuronal
      degeneration induced by excitotoxins or beta-amyloid peptide in cortical
      cultures.

PMID- 10884511
TI  - Extracellular ATP reduces optically monitored electrical signals in hippocampal
      slices through metabolism to adenosine.
AB  - Electrical signals in rat hippocampal slices were optically monitored using a
      voltage-sensitive dye to determine whether extracellular ATP exhibits direct
      effects through its own receptors or indirect effects after its hydrolysis to
      adenosine. The dentate gyrus was stimulated and electrical signals in the CA1 and
      the CA3 region were analyzed. The signals were divided into two components: a
      transient component peaking within 10 ms (fast component) and a subsequent
      sustained component (slow component). ATP (10 to 100 microM) inhibited both the
      fast and the slow components in the CA1 region by about 30% and 70%,
      respectively. ADP, AMP and adenosine also inhibited the fast and the slow
      components. The inhibition by ATP was antagonized by aminophylline and other
      adenosine receptor antagonists, and by alpha,beta-methylene ADP, an inhibitor of
      5'-nucleotidases. These results suggest that extracellular ATP inhibits neuronal
      electrical signals in hippocampal slices after its metabolism to adenosine.

PMID- 10884512
TI  - Caffeine blockade of the thermal antihyperalgesic effect of acute amitriptyline
      in a rat model of neuropathic pain.
AB  - In the present study, we sought to determine whether administration of caffeine,
      a non-selective adenosine receptor antagonist, would affect the thermal
      antihyperalgesic efficacy of acute amitriptyline in a rat model of neuropathic
      pain. Rats were rendered neuropathic by unilateral tight ligation of the fifth
      and sixth lumbar spinal nerves, and tested for thermal hyperalgesia using a
      focused beam of light. Systemic administration of caffeine (1.5-7.5 mg/kg), at
      the same time as amitriptyline, blocked the thermal antihyperalgesic effect of 10
      mg/kg amitriptyline. The greatest degree of block exerted by caffeine was
      observed with 3.75 mg/kg (100% block), a dose that had no observable intrinsic
      effect. Spinal administration of amitriptyline (60 microg) exhibited a mild
      antihyperalgesic effect that was unaffected by pretreatment with intrathecal
      caffeine (100 microg). Peripheral administration of amitriptyline into the
      neuropathic paw (under brief anesthesia) produced an antihyperalgesic effect at
      both 30 and 100 nmol, with a greater effect being observed at 100 nmol.
      Coadministration of caffeine (1500 nmol) partially antagonized the effects of
      both doses of amitriptyline. The results of this study suggest that the thermal
      antihyperalgesic effect of acute amitriptyline in this model may involve
      enhancement of an endogenous adenosine tone. This involvement is important in
      light of the widespread consumption of caffeine, which may potentially act to
      reduce the benefits of amitriptyline in the treatment of neuropathic pain.

PMID- 10884513
TI  - Pharmacological evaluation of aerosolized cannabinoids in mice.
AB  - The reemergence on the debate of the use of marijuana for medicinal purposes has
      been the impetus for developing an acceptable delivery form of aerosolized
      cannabinoids. The goals of the present study were to: (1) develop and
      characterize the physical properties of an aerosolized form of Delta(9)
      tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent present
      in marijuana; and (2) assess the pharmacological effects of cannabinoid
      inhalation in mice. A Small Particle Aerosol Generator (SPAG) nebulizer, used to
      generate the aerosol, had an output of approximately 0.154 mg/l of aerosolized
      Delta(9)-THC with a 2.0 microm mass median aerodynamic diameter and a 2.2
      geometric standard deviation (GSD). Virtually all the particles were less than
      5.0 microm in diameter suggesting that they were sufficiently small to penetrate
      deeply into the lungs. Inhalation exposure to aerosolized Delta(9)-THC in mice
      elicited antinociceptive effects that were dependent on concentration and
      exposure time with an estimated Delta(9)-THC dose of 1.8 mg/kg. On the other
      hand, inhalation exposure to Delta(9)-THC failed to produce two other indices
      indicative of cannabinoid activity, hypothermia and decreases in spontaneous
      locomotor activity. The antinociceptive effects occurred within 5 min of exposure
      and lasted approximately 40 min in duration. The cannabinoid receptor antagonist
      N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H
      pyrazole-3-carboxamide HCl (SR 141716A), but not naloxone, blocked these
      antinociceptive effects (AD(50)=0.09 mg/kg) indicating a cannabinoid receptor
      mechanism of action. Similarly, inhalation exposure to a water soluble
      cannabinoid analog, 3-(5'-cyano-1', 1'dimethylheptyl)-1-(4-N-morpholinobutyrloxy)
      Delta(8)-te trahydrocann abinol (O-1057), produced antinociception that was
      blocked by SR 141716A. These results demonstrate that the development of an
      aerosolized form of cannabinoids for human medicinal use is feasible.

PMID- 10884514
TI  - Muscarinic antagonists in substantia nigra influence the decarboxylation of L
      dopa in striatum.
AB  - This study was designed to investigate whether anticholinergic drugs acting at
      the level of the substantia nigra can affect basal extracellular dopamine
      concentrations and the levodopa (L-dopa)-induced increases in dopamine levels in
      the striatum. Dual probe in vivo microdialysis in freely moving rats was used.
      One microdialysis probe was implanted in the substantia nigra and the other in
      the ipsilateral striatum. Muscarinic receptor antagonists were perfused into the
      substantia nigra and changes in neurotransmitter levels in the substantia nigra
      and at the axon terminals in the striatum were monitored simultaneously. Nigral
      perfusion of the non-selective muscarinic receptor antagonist trihexyphenidyl (1
      mM) produced an increase in extracellular dopamine and gamma-aminobutyric acid
      (GABA) levels in the substantia nigra. Perfusion with the muscarinic M(1)
      receptor antagonist telenzepine (0.1 microM) produced a significant decrease in
      nigral dopamine and GABA levels in the substantia nigra. The muscarinic M(2)
      receptor antagonist methoctramine (75 microM) produced an increase in dopamine
      levels in the substantia nigra. No significant changes in nigral extracellular
      GABA levels were observed. The L-dopa-induced increases in extracellular dopamine
      levels in the striatum were clearly attenuated under nigral perfusion of these
      drugs. This in vivo study demonstrates that anticholinergic drugs perfused at the
      level of the substantia nigra can modulate dopamine and GABA levels and attenuate
      the L-dopa decarboxylation in the striatum, possibly via modulation of the
      nigrostriatal dopaminergic system. We add further evidence that the substantia
      nigra is an important site of action of antimuscarinic drugs. The attenuation of
      L-dopa-induced dopamine release in the striatum exerted by nigral perfusion of
      these antimuscarinic drugs is probably mediated via different mechanisms. This
      attenuation is regarded as a beneficial effect of the muscarinic antagonists as
      adjuncts to L-dopa in Parkinson's disease treatment. We postulate that drugs that
      enhance dopamine release, after L-dopa administration, in a less extreme way than
      L-dopa administered on its own could prevent further neurodegeneration and
      dyskinesias thought to result from extremely high extracellular dopamine levels
      following L-dopa treatment.

PMID- 10884515
TI  - Role of nitric oxide in diabetes-induced attenuation of antinociceptive effect of
      morphine in mice.
AB  - The study was designed to investigate the role of nitric oxide (NO) in the
      diabetes-induced decrease of the antinociceptive effect of morphine. The
      nociceptive threshold in diabetic and non-diabetic mice was measured in the tail
      flick test. Streptozotocin (200 mg/kg i.p.) was administered to induce
      experimental diabetes in the mice. Four weeks after the administration of
      streptozotocin, the tail-flick test was performed and urinary nitrite
      concentration was estimated using Greiss reagent. Experimental diabetes markedly
      decreased the antinociceptive effect of morphine (10 microg in 5 microl/mice
      i.c.v.) and significantly increased the urinary nitrite concentration.
      Administration of aminoguanidine (12 mg/mice) markedly improved the
      antinociceptive effect of morphine and attenuated the increase in urinary nitrite
      concentration in diabetic mice. It may be tentatively concluded that an increase
      in NO formation may be responsible for the observed decrease in antinociceptive
      effect of morphine in diabetic mice.

PMID- 10884516
TI  - Decrease of hindpaw withdrawal latency by cocaine- and amphetamine-regulated
      transcript peptide to the mouse spinal cord.
AB  - Immunohistochemical studies with the use of an antiserum against the cocaine- and
      amphetamine-regulated transcript (CART) peptide-(55-102) showed an abundance of
      CART-immunoreactive fibers in the mouse dorsal horn laminae I and II. A few CART
      positive somata were scattered in the dorsal horn and around the central canal.
      Intrathecal injection of the CART peptide-(55-102) at doses 3, 10 and 100 ng
      caused a dose-dependent and significant decrease of paw withdrawal latency;
      whereas, saline injection was without significant effect. Our results provide the
      first evidence that CART-immunoreactive fibers are present in the dorsal horn and
      that the peptide administered intrathecally produces hyperalgesia, as assessed by
      paw withdrawal latency in mice.

PMID- 10884517
TI  - Modification of dopamine D(1) receptor knockout phenotype in mice lacking both
      dopamine D(1) and D(3) receptors.
AB  - Experimental evidence suggests that dopamine D(1) and D(3) receptors may interact
      in an opposing or synergistic fashion. To investigate interactions between both
      receptors in behaviour, we have used dopamine D(1) and D(3) receptor knockout
      mice to generate mice lacking both receptors. D(1)(-/-)D(3)(-/-) mice were
      viable, fertile and showed no gross morphological abnormalities. In an open
      field, they exhibited lower activity than wild-type, D(1)(-/-) and D(3)(-/-)
      mice. D(1)(-/-)D(3)(-/-) mice performed equally poorly in the rotarod and Morris
      water maze tasks as their D(1)(-/-) littermates. Basal locomotor activity and
      anxiety-like behaviour were normal in D(1)(-/-)D(3)(-/-) mice. Combined deletion
      of both receptors abolished the exploratory hyperactivity and anxiolytic-like
      behaviour of dopamine D(3) receptor mutant phenotype and further attenuated the
      low exploratory phenotype of D(1)(-/-) mice. These results imply an interaction
      of both receptors in the expression of exploratory behaviour in a novel
      environment, and the need for the presence of intact dopamine D(1) receptor for
      the expression of certain behaviours manifested in dopamine D(3) receptor mutant
      phenotype. In addition, dopamine D(1) receptor, but not dopamine D(3) receptor,
      is involved in the ability to perform on the rotarod and spatial learning.

PMID- 10884518
TI  - Antidyskinetic effect of JL-18, a clozapine analog, in parkinsonian monkeys.
AB  - Clozapine reduces L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesias in
      parkinsonian patients. To test if the antidyskinetic effect of clozapine is
      related to antagonism at the dopamine D(4) receptor, we investigated the effect
      of 8-methyl-6-(4-methyl-1-piperazinyl)-11H-pyrido[2,3-b][1, 4]benzodiazepine (JL
      18), a structural analog of clozapine which is more selective for this receptor.
      Four 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-treated cynomolgus
      monkeys with a stable parkinsonian syndrome and reproducible dyskinesias to L
      Dopa were used in this study. They were injected subcutaneously (s.c.) with L
      Dopa methyl ester (125 mg per animal) plus benserazide (50 mg per animal; L
      Dopa/benserazide) alone or in combination with JL-18 (at the doses of 0.1, 0.3,
      or 0.9 mg/kg, s.c.). Subcutaneous injection of sterile saline was used as
      control. L-Dopa/benserazide increased locomotion and improved parkinsonism but
      also induced dyskinesias. Co-administration of JL-18, at low doses (0.1, 0.3
      mg/kg) with L-Dopa/benserazide, produced a dose-dependent reduction in L-Dopa
      induced dyskinesias without a parallel return to parkinsonism. The present
      results suggest that novel selective dopamine D(4) receptor antagonists may
      represent a useful tool to reduce L-Dopa-induced dyskinesias.

PMID- 10884519
TI  - Vasorelaxant and antiproliferative effects of berberine.
AB  - The present study was intended to examine the relaxant effects of berberine in
      rat isolated mesenteric arteries. Berberine produced a rightward shift of the
      concentration-response curve to phenylephrine and significantly reduced the
      maximal contractile response to phenylephrine. Berberine (10(-7)-3x10(-5) M) also
      relaxed the phenylephrine- and 9,11-dideoxy-11alpha, 9alpha-epoxy
      methanoprostaglandin F(2alpha)-precontracted arteries with respective IC(50)
      values of 1.48+/-0.16x10(-6) and 2.23+/-0. 22x10(-6) M. Removal of a functional
      endothelium significantly attenuated the berberine-induced relaxation (IC(50):
      4.73+/-0. 32x10(-6) M) without affecting the maximum relaxant response.
      Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) or methylene blue
      reduced the relaxant effect of berberine, and L-arginine (10(-3) M) partially
      antagonized the effect of L-NAME. In contrast, pretreatment with 10(-6) M
      glibenclamide or 10(-5) M indomethacin had no effect. Berberine (10(-5) M)
      reduced over by 50% the transient contraction induced by caffeine or
      phenylephrine in endothelium-denuded rings bathed in Ca(2+)-free Krebs solution.
      Pretreatment with putative K(+) channel blockers, such as tetrapentylammonium
      ions (1-3x10(-6) M), 4-aminopyridine (10(-3) M), or Ba(2+) (3x10(-4) M),
      significantly attenuated the berberine-induced relaxation in endothelium-denuded
      arteries. In contrast, tetraethylammonium ions (3x10(-3) M), charybdotoxin (10(
      7) M) or glibenclamide (10(-6) M) were without effect. Berberine reduced the high
      K(+)-induced sustained contraction and the relaxant response to berberine was
      greater in rings with endothelium (IC(50): 4.41+/-0.47x10(-6) M) than in those
      without endothelium (IC(50): 8.73+/-0.74x10(-6) M). However, berberine (10(-6)
      10(-4) M) did not affect the high-K(+)-induced increase of intracellular [Ca(2+)]
      in cultured aortic smooth muscle cells. Berberine did not affect active phorbol
      ester-induced contraction in Ca(2+)-free Krebs solution. In addition, berberine
      inhibited proliferation of cultured rat aortic smooth muscle cells with an IC(50)
      of 2.3+/-0.43x10(-5) M. These findings suggest that berberine could act at both
      endothelium and the underlying vascular smooth muscle to induce relaxation.
      Nitric oxide from endothelium may account primarily for the berberine-induced
      endothelium-dependent relaxation, while activation of tetrapentylammonium-, 4
      aminopyridine- and Ba(2+)-sensitive K(+) channels, inhibition of intracellular
      Ca(2+) release from caffeine-sensitive pools, or a direct relaxant effect, is
      likely responsible for the berberine-induced endothelium-independent relaxation.
      Mechanisms related to either Ca(2+) influx or protein kinase C activation may not
      be involved. Both vasorelaxant and antiproliferative effects may contribute to a
      long-term benefit of berberine in the vascular system.

PMID- 10884520
TI  - The galanin receptor antagonist M40 blocks the central cardiovascular actions of
      the galanin N-terminal fragment (1-15).
AB  - It has been shown that galanin plays a role in central cardiovascular regulation.
      Galanin administered centrally induces an increase of heart rate and a weak
      vasodepressor response, whereas the N-terminal galanin fragment (1-15) elicits
      vasopressor effects and tachycardia. Furthermore, it has been shown that galanin
      (1-15), but not galanin-(1-29), decreases the baroreceptor reflex sensitivity.
      Since these data demonstrate that both galanin and its N-terminal fragment (1-15)
      exert a different modulation on central cardiovascular control, the aim of this
      work has been to study if the specific galanin receptor antagonist Galanin-(1-12)
      Pro-(Ala-Leu)(2)-Ala]-amide (M40) could modulate their cardiovascular actions.
      Urethane anaesthetized rats were injected intracisternally and the changes in
      mean arterial pressure and heart rate were monitored. Two doses of M40 alone have
      been tested for their cardiovascular effects. With the dose of 1.0 nmol, a
      significant tachycardia was observed (P<0.001), but 0.1 nmol was ineffective.
      This suggests a possible agonistic effect for the higher doses of M40. The
      galanin receptor antagonist M40 at the dose of 0.1 nmol failed to modify the weak
      vasodepressor effects and tachycardia induced by 3.0 nmol of galanin-(1-29).
      However, the same dose completely blocked the vasopressor and tachycardic
      responses elicited by 3.0 nmol of galanin-(1-15). These data show that M40
      differentially counteracts the central cardiovascular responses of the galanin
      fragment and give a functional support for the existence of galanin receptor
      subtypes within the brainstem. Therefore, the present findings can be explained
      on the basis that the cardiovascular actions of galanin-(1-29) could be mediated
      by one type of galanin receptor, whereas a galanin receptor subtype that
      recognizes N-terminal fragments of galanin may mediate the actions of galanin-(1
      15).

PMID- 10884521
TI  - Intragastric administration of heparin enhances gastric ulcer healing through a
      nitric oxide-dependent mechanism in rats.
AB  - Our preliminary finding indicated that intravenous (i.v.) injection of heparin
      increased gastric ulcer healing in rats. However, the anticoagulant action of
      i.v. heparin could produce complications in ulcer patients if the drug was used
      as an anti-ulcer agent. The present study aimed to investigate whether
      intragastric (i.g.) administration of heparin, known to have no anticoagulant
      activity, would have the similar ulcer healing effect and the relationship of
      this effect, if any, with nitric oxide (NO), a substance suggested to be
      important for ulcer healing. Heparin (100, 500, 1000 U/kg, i.g. ) administered
      once daily for 4 days accelerated the healing of gastric ulcer induced by acetic
      acid in Sprague-Dawley rats, which was accompanied by an increase in mucosal
      proliferation and regeneration at the ulcer margin, microvessel number both at
      the ulcer margin and base, and the thickness of mucus layer. Both activity and
      content, but not the mRNA of constitutive nitric oxide synthase (cNOS) in the
      gastric mucosa were enhanced. L-N(G)-nitroarginine methyl ester (L-NAME), an
      inhibitor of NOS activity blocked the cNOS activity activated by heparin and
      reversed the beneficial effects of heparin on ulcer healing. The bleeding time
      was not altered by i.g. heparin. These findings demonstrate that i.g. heparin
      promotes the healing processes of gastric ulcer. Such effect is suggested to act
      through the stimulation of mucosal cNOS activity. In addition, i.g. heparin is
      better than i.v. heparin without the potential anticoagulation effect.

PMID- 10884522
TI  - Systemic and intratubular effects of cyclosporin-A and tacrolimus on the rat
      kidney.
AB  - Cyclosporin-A and tacrolimus can cause hypertension and renal failure through
      endothelin receptors. The importance of tubular function was never investigated.
      The aim of this study was to compare the effects of intratubular injection of
      cyclosporin-A and tacrolimus with effects observed during systemic infusion. In
      20 rats, either cyclosporin-A or tacrolimus was infused, 30 and 1 mg/kg i.v.,
      respectively, in 30 min. Before and after administration, glomerular filtration
      rate, single nephron filtration rate, proximal and distal absolute reabsorption
      and percent reabsorption were measured by clearance and micropuncture techniques.
      In 22 other rats, single nephron filtration rate, absolute reabsorption, percent
      reabsorption, were measured at the last proximal and early distal tubules before
      and during intraluminal microinjection of either cyclosporin-A or tacrolimus.
      During cyclosporin-A and tacrolimus i.v. infusion, glomerular filtration rate
      fell from 536+/-43 to 448+/-37 microl/min (P<0.026) and from 408+/-33 to 284+/-81
      microl/min (P<0. 02), single nephron filtration rate from 26.4+/-2.0 to 20.6+/
      1.9 (P<0.002) and from 21.6+/-2.2 to 17.4+/-2.0 nl/min, respectively (P<0.02).
      The last proximal absolute reabsorption remained unchanged with cyclosporin-A
      (16.8+/-2.2 vs. 15.1+/-1.7 nl/min, P>0.444), but was slightly reduced by
      tacrolimus (14.4+/-1.7 vs. 11.3+/-1.7 nl/min, P<0.05). During microinjection,
      single nephron filtration rate was increased by cyclosporin-A (20+/-1 vs. 63+/-8
      nl/min, P<0.0001), and tacrolimus (from 17+/-2 to 49+/-9 nl/min, P<0.0001), and
      so was reabsorption, independent of the sampling site. Cyclosporin-A and
      tacrolimus, indeed, raise single nephron filtration rate directly when injected
      intraluminally. Since this effect occurs in the direction opposite to that
      recorded during systemic infusion, it must be mediated through different
      pathways. The i.v. infusion of cyclosporin-A, but not tacrolimus, impairs
      glomerulo-tubular balance.

PMID- 10884523
TI  - Involvement of the renal kallikrein-kinin system in K(+)-induced diuresis and
      natriuresis in anesthetized rats.
AB  - Intravenous infusion of a high-K(+) solution (67.5 mM KCl, 67.5 mM NaCl) to
      anesthetized rats increased urine volume by 47.6% after 60 min, compared with
      infusion of a Na(+) solution (135 mM NaCl). This treatment also increased urinary
      excretion of Na(+) by 32.2%, in parallel with an increase in excretion of K(+) or
      Cl(-). Urinary excretion of kallikrein increased within 60 min after the start of
      K(+) infusion. A bradykinin B(2) receptor antagonist, 8-[3-[N-[(E)-3-(6
      acetamidopyridin-3-yl)acryloylglycyl]-N-me thylamino ]-2,6-dichlorobenzyloxy]-2
      methylquinoline (FR173657; 1.0 mg/kg, i.v. ), inhibited the K(+)-induced diuresis
      and natriuresis by 41.0% and 26.7%, respectively. These results indicate that
      K(+) load induces diuresis and natriuresis through the renal kallikrein-kinin
      system in rats.

PMID- 10884524
TI  - Involvement of haemoxygenase-1 in ozone-induced airway inflammation and
      hyperresponsiveness.
AB  - Haemoxygenase catalyses the degradation of haem to bilirubin, and the inducible
      form of haemoxygenase, haemoxygenase-1, is highly induced in response to
      oxidative stress in vitro. The effect of haemoxygenase-1 in oxidant stress in
      vivo is not known. We determined the effect of exposure to ozone on haemoxygenase
      1 expression, and the modulation of haemoxygenase-1 expression on ozone-induced
      lung neutrophilia and bronchial hyperresponsiveness in rats. Ozone caused a
      significant induction of lung haemoxygenase-1. Pretreatment of rats with
      haemoglobin, a potent inducer of haemoxygenase-1, resulted in a large induction
      of haemoxygenase-1 expression, and inhibited ozone-induced neutrophilia and
      bronchial hyperresponsiveness. Tin protoporphyrin, a competitive inhibitor of
      haemoxygenase, reduced the expression of haemoxygenase-1 induced by haemoglobin.
      It enhanced ozone-induced neutrophilia, but not the bronchial
      hyperresponsiveness, and reduced the protective effect of haemoglobin. Overall,
      there was an association between bronchial hyperresponsiveness and the
      neutrophilic response. These data indicate that haemoxygenase-1 plays an
      important role in modulating the effects of an oxidant, such as ozone in the
      lungs.

PMID- 10884525
TI  - Involvement of kinins, mast cells and sensory neurons in the plasma exudation and
      paw oedema induced by staphylococcal enterotoxin B in the mouse.
AB  - Intraplantar injection of staphylococcal enterotoxin B induces long-lasting
      oedema mediated by both cyclooxygenase and lipoxygenase products as well as by
      neuropeptides from sensory nerves. This study was undertaken to further clarify
      the role of peripheral primary afferent sensory nerves in staphylococcal
      enterotoxin B (25 microg/paw)-induced plasma extravasation and oedema formation.
      The tachykinin NK(1) receptor antagonist (S)-1-[2-[3-(3, 4-dichlorophenyl)-1 (3
      isopropoxyphenylacetyl)piperidin-3-yl] ethyl]-4-phenyl-1 azoniabicyclo
      [2.2.2]octane cloride (SR140333; 120 nmol/kg, s.c.+120 nmol/kg, i.v.)
      significantly inhibited plasma exudation and paw oedema evoked by staphylococcal
      enterotoxin B. The tachykinin NK(2) receptor antagonist (S)-N-methyl-N[4-(4
      acetylamino-4-phenyl piperidino)-2-(3, 4-dichlorophenyl)butyl]-benzamide
      (SR48968) had no effect on the staphylococcal enterotoxin B-induced responses.
      The bradykinin B(2) receptor antagonist D-Arg-[Hyp(3),Thi(5),D
      Tic(7),Oic(8)]bradykinin (Hoe 140; 400 nmol/kg, i.v.) significantly reduced
      staphylococcal enterotoxin B-induced responses. The magnitude of the inhibition
      observed with Hoe 140 alone was similar to that caused by concomitant treatment
      of animals with SR140333 and Hoe 140, suggesting that there is a final common
      pathway. Additionally, SR140333 given alone reduced bradykinin (3 nmol/paw)
      induced paw oedema. The vanilloid receptor antagonist N-[2-(4-chlorophenyl)
      ethyl]-1,3,4,5-tetrahydro-7, 8-dihydroxy-2H-2-benzazepine-2-carbothioamide
      (capsazepine; 100 micromol/kg) significantly reduced staphylococcal enterotoxin B
      induced responses. The 5-HT receptor antagonist methysergide (10 mg/kg, i.v.) and
      the histamine H(1) receptor antagonist mepyramine (10 mg/kg, i.v.) produced a
      significant reduction in paw oedema whereas plasma exudation was reduced only by
      methysergide. In diabetic mice, exudation and oedema evoked by staphylococcal
      enterotoxin B were markedly reduced. Acute administration of insulin (20 UI/kg,
      s.c., 30 min before) did not restore the increased permeability induced by
      staphylococcal enterotoxin B. We conclude that plasma exudation and paw oedema in
      response to staphylococcal enterotoxin B are a consequence of a complex
      neurogenic response involving direct activation of vanilloid receptors on sensory
      nerves, release of kinins and subsequent activation of bradykinin B(2) receptors
      at a prejunctional level, and direct or indirect degranulation of mast cells.

PMID- 10884526
TI  - Anti-inflammatory and analgesic effects of the phosphodiesterase 4 inhibitor
      rolipram in a rat model of arthritis.
AB  - There has been much interest in strategies which modulate tumour necrosis factor
      alpha (TNF-alpha) levels and/or function in rheumatoid arthritis. The elevation
      of intracellular levels of cyclic AMP in leukocytes by phosphodiesterase 4
      inhibitors is accompanied by significant inhibition of the production of TNF
      alpha. Nevertheless, these drugs may enhance the hyperalgesia induced by a range
      of inflammatory mediators, including TNF-alpha. In the present study, we examined
      the effects of the phosphodiesterase 4 inhibitor rolipram on the local
      inflammatory infiltrate and hyperalgesia in a rat model of adjuvant-induced
      arthritis. Rolipram (3 mg/kg) was administered by oral gavage from day 10 to 14
      after disease induction. Pretreatment with rolipram abrogated oedema formation
      and significantly inhibited hyperalgesia. Histopathological analysis revealed a
      marked inhibition of cellular influx as well as bone and cartilage destruction.
      Serum and local TNF-alpha levels were suppressed in treated animals whereas there
      were little changes in interleukin-1beta levels. Although cyclic AMP elevating
      agents may affect nociceptor threshold to increase the hyperalgesic responses
      acutely, they also possess significant anti-inflammatory activity, which may
      hinder local mediator release and/or action. The anti-inflammatory effects of
      rolipram predominate during this chronic arthritis model in the rat.

PMID- 10884527
TI  - Systemic anti-inflammatory effect of somatostatin released from capsaicin
      sensitive vagal and sciatic sensory fibres of the rat and guinea-pig.
AB  - The systemic anti-inflammatory effect induced by antidromic sensory nerve
      stimulation was investigated in rats and guinea-pigs. In atropine-pretreated
      rats, bilateral antidromic stimulation of vagal afferent fibres (8 Hz, 20 min, at
      C-fibre strength) inhibited plasma extravasation induced by 1% mustard oil on the
      acutely denervated hindlegs by 36.45+/-3.95%. Both the prevention of this
      inhibitory effect by cysteamine pretreatment and the stimulation-evoked rise of
      plasma somatostatin-like immunoreactivity in the two species suggest a mediator
      role of neural somatostatin. Since this response was blocked by systemic
      capsaicin pretreatment and slightly reduced after subdiaphragmal vagotomy,
      participation of thoracic capsaicin-sensitive afferents is indicated. In guinea
      pigs pretreated with guanethidine and pipecuronium, antidromic sciatic nerve
      stimulation induced 45.46+/-5.08% inhibition on the contralateral leg and
      increased plasma somatostatin-like immunoreactivity. It is concluded that
      somatostatin released from the activated vagal capsaicin-sensitive sensory nerve
      terminals of the rat and somatic nerves of the guinea-pigs exerts a systemic
      humoral function.

PMID- 10884528
TI  - World report on women's health 2000.

PMID- 10884529
TI  - The girl child.
AB  - The health of the girl child is a concern for obstetrician-gynecologists.
      Pediatric gynecologic conditions deserve special attention. The obstetric
      performance of the adult woman depends in large part on the health and healthcare
      of the girl child. Gender discrimination against the girl child violates her
      human rights and adversely impacts on her health and her life. The profession has
      a social responsibility to advocate for the girl child's right to health.

PMID- 10884530
TI  - Recognizing adolescents' 'evolving capacities' to exercise choice in reproductive
      healthcare.
AB  - All countries (except Somalia and the USA) have adopted the UN Convention on the
      Rights of the Child, which usually applies to individuals aged under 18 years.
      The Convention requires governments to 'respect the responsibilities, rights and
      duties of parents [or others acting as parents] ellipsis in a manner consistent
      with the evolving capacities of the child'. Many adolescents gain capacity to
      make decisions for themselves concerning reproductive and sexual health services,
      and to decide issues of confidentiality. Immature adolescents must be given usual
      protections. The Convention sets a legal limit on parental power to deny capable
      adolescents reproductive and sexual health services. The question whether an
      adolescent is a 'mature minor' must be decided by health service providers
      independently of parental judgment. The specific duties of government and health
      service providers to implement adolescent rights regarding their reproductive and
      sexual health needs are examined.

PMID- 10884531
TI  - The implementation of reproductive health programs: experiences, achievements and
      challenges.
AB  - As a fundamental element of population strategies for international development,
      reproductive health has received much recognition since the International
      Conference on Population and Development held in Cairo in 1994. Nevertheless,
      much remains to be done to improve the understanding of the concept of
      reproductive health, support reproductive rights, operationalize reproductive
      healthcare within basic health services and promote a more conducive social,
      cultural and economic environment, especially for women and girls, to enable the
      attainment of reproductive health. Collaboration between governments and non
      governmental organizations will be crucial and obstetrician-gynecologists have a
      unique role, through service provision, review of regulatory frameworks,
      education and advocacy, for the promotion of reproductive health.

PMID- 10884532
TI  - Decreasing the need for abortion: challenges and constraints.
AB  - Voluntary abortion is the most controversial act in the entire field of medical
      practice, although today, it is a practice that, under different conditions, has
      been legalized in more than 100 countries, mostly in the developed world. The
      United Nations has agreed that in no case should abortion be promoted as a method
      of family planning and, therefore, it should be utilized only when contraception
      has failed. Overall, 61% of humanity lives in countries where abortion is legal
      and widely available; 14% in countries where termination is allowed to protect a
      woman's health; physical, mental, or both; 21% in countries where it can be
      performed only to save the mother's life and 4% in countries where abortion is
      not permitted at all. Restrictive legislation, per se, does not represent a valid
      deterrent to prevent abortion, while it may contribute to an increase in
      morbidity and mortality associated with pregnancy. In addition, because abortion
      is outlawed, nothing is done to actively reduce the reasons leading to it.
      Indeed, the countries with the lowest abortion rates are those where, on the one
      hand, pregnancy termination is legal and, on the other, sex education and
      contraceptive knowledge are widely spread.

PMID- 10884533
TI  - Emergency contraception in clinical practice: global perspectives.
AB  - Access to reliable contraception is often unavailable. Unsafe abortion yearly
      causes death for thousands and disabling illness for millions worldwide.
      Insufficient information, negligence, inappropriate contraception, poverty and
      poor education contribute to these serious sequelae of unintended pregnancy.
      Identification of those at risk, the provision of appropriate information and
      access to emergency contraception (EC), and male involvement are emphasized.
      Improved knowledge, better attitudes, enhanced practice of EC, and determined
      providers might meet the requirements of the next century.

PMID- 10884534
TI  - Women and reproductive health in a graying world.
AB  - Gender differences in longevity suggest that the health problems in both
      developed and developing countries will largely be the problems of older women.
      As life expectancy increases, the important causes of death and ill health
      change. Older women's health issues and reproductive health needs are different
      from those of younger women. Biological susceptibility to various conditions also
      differs between the sexes. Monitoring of differences in incidence can better
      direct preventive efforts and contribute to improving the quality of life for
      aging women worldwide.

PMID- 10884535
TI  - Environmental influence on reproductive health.
AB  - A rise in industrialization and the consequent environmental pollution, an
      increase in the use of synthetic chemicals and repeated exposure to hazardous
      compounds at the workplace and at home adversely affects reproductive health.
      Biohazardous compounds, some of which act as endocrine disrupters, are being
      increasingly implicated in infertility, menstrual irregularities, spontaneous
      abortions, birth defects, endometriosis and breast cancer. In some cases, women
      are at a greater risk than men, especially with the rise in environmental
      estrogens. Only a fraction of these chemicals have been adequately examined for
      toxicity and for synergistic effects due to multiple exposures. There is a need
      for a greater awareness and vigilance of the effects of environmental pollution
      on reproductive health.

PMID- 10884536
TI  - Women's reproductive health: monotheistic religious perspectives.
AB  - It is important to those who practice reproduction techniques to learn about the
      different religious attitudes related to reproductive health problems. Religion
      exerts an influence on civil authorities in the field of reproduction such as
      prevention or procreation and in issues such as abortion and infertility therapy.
      The Jewish attitude towards reproduction can be learned from the fact that the
      first commandment of God to Adam was be fruitful and multiply. Judaism allows the
      practice of all techniques of assisted reproduction when the oocyte and sperm
      originate from the wife and husband, respectively. All Rabbinical rulings permit
      the use of contraception for medical indications. Economic difficulties and
      inconveniences of raising children are not indications for birth control
      practice. According to Judaism abortion on demand is forbidden but it may be
      performed if the mother's life is in danger. The attitude toward reproductive
      practice is different among the different divisions of Christianity. The practice
      of assisted reproduction is not accepted by the Vatican, however, it may be
      practiced by Protestant, Anglican and other Denomination's. According to the
      Roman Catholic doctrine the primary purpose of marriage is procreation. The
      contraceptive act destroys the potential of producing new life by sexual
      intercourse and violates the purpose of marriage and, therefore, is a sin against
      nature. The Christian tradition views the embryo as a human being since
      conception and, therefore, abortion is strictly forbidden. According to Islam,
      the procedure of IVF and ET is acceptable, however, it can be preformed only if
      it involves the husband and the wife. It allows contraception practice only under
      some circumstances and only in some special cases abortion can be preformed.
      Religion, being concerned with affairs that are regarded as extraordinary and as
      having unique importance in life, is an intrinsic aspect of the culture of all
      societies, religious groups, however, still exert influence on the civil
      authorities in issues of reproduction such as contraception, procreation,
      abortion, and infertility therapy. They have been active in pressing their
      bioethical positions on the public arena in pluralistic societies. Developments
      in science and technology in reproduction raise new religious questions that do
      not always have clear answers. The role of theology in bioethics is foremost to
      clarify for the different religious communities the perceived attitudes toward
      these developments. Therefore, it is important to those who practice reproduction
      techniques to learn about the different religious attitudes related to
      reproductive health problems.

PMID- 10884537
TI  - Maternal survival in developing countries: what has been done, what can be
      achieved in the next decade.
AB  - Every year, approximately 600000 women die of pregnancy-related causes - 98% of
      these deaths occur in developing countries. For every woman who dies, at least 30
      suffer injuries and often, permanent disability. The challenge today is to re
      orient programmes on priority interventions, and to mobilize sufficient resources
      for their implementation. More resources have been put into antenatal care than
      into delivery care and the management of complications of births and unsafe
      abortions. This article describes the effective strategies for reducing maternal
      death, their policy requirements and programmatic implications, and provides
      examples of successful developing country programmes. Priority interventions
      include: (1) improving availability and use of essential obstetric care for the
      management of complications; (2) strengthening family planning services; (3)
      ensuring skilled attendance at birth; (4) promoting women-friendly health
      services; (5) increasing district-level planning with community participation;
      and (6) monitoring process with process indicators. Finally, the promotion of
      safe motherhood as a right is of crucial importance. Needed now is political
      commitment as well as coordinated action for the implementation of large-scale
      programmes in low-income countries.

PMID- 10884538
TI  - Female genital mutilation (FGM) management during pregnancy, childbirth and the
      postpartum period.
AB  - Female genital mutilation (FGM) is a traditional practice with serious health
      consequences to women that is still practiced in 28 countries with approximately
      2 million girls exposed to the practice annually. The complications of FGM cause
      suffering to the woman all her life. Pregnancy, childbirth and the postpartum
      period are particularly important as there is increased risk of mortality and
      morbidity from FGM complications. Although the overall strategy should be to
      eliminate the practice completely, the healthcare providers and policy makers in
      the meantime should not only be aware but also well trained in the management of
      FGM complications to decrease the risk of mortality and serious morbidity.

PMID- 10884539
TI  - Sociobiological variables and pregnancy outcome.
AB  - Recent advances are beginning to shed light on the mechanisms whereby adverse
      psychosocial factors can influence pregnancy outcome. High levels of maternal
      stress have been linked to endocrine disturbances, which in turn increases the
      risk of preterm labor considerably. These observations have been supported by
      experimental animal models. Birth weight is subject to considerable ethnic
      variation, and on its own is a nonspecific indicator of pregnancy outcome. The
      benefits of social and psychological intervention have been best documented in
      the intrapartum situation, whereas antenatal intervention is most likely to be of
      benefit when focused on improving socioeconomic conditions and access to
      healthcare providers.

PMID- 10884540
TI  - Safe motherhood in Sri Lanka: a 100-year march.
AB  - The present safe motherhood status in Sri Lanka has been achieved by a series of
      activities for health and social development during the past century. While
      ancient and traditional religious, as well as cultural concepts provided a sound
      foundation, it was the policies that focused on human development that resulted
      in reducing the maternal mortality rate to 2.4 per 10000 live births, and the
      infant mortality rate to 16.5 per (1000) live births. Maternal and Child Health
      (MCH) services were initially closely linked to improvements in the healthcare
      infrastructure and social development, while family planning introduced in 1953
      enhanced its progress further. With MCH integrated into reproductive health, the
      march towards a safer motherhood in Sri Lanka will require the implementation of
      new policies and strategies.

PMID- 10884541
TI  - Present and future of maternal mortality in Latin America.
AB  - Twenty-three thousand maternal deaths per year in Latin America and the Caribbean
      reflects clearly the critical situation in this part of the world. Although we
      don't know exactly how many women die every year from pregnancy and childbirth,
      it is clear that the majority of these women are from low socioeconomic
      backgrounds, live in remote places and have a low level of education.
      Hemorrhages, infections and hypertension induced by pregnancy are the most common
      causes of maternal mortality. These pathologies can in many cases be prevented if
      there is a will for a positive change that involves different sectors related
      with health. The role of the scientific societies, and the role of FIGO through
      the 'Save the Mothers' Project are of extreme importance, assuming a chief role
      and compromise that can help in the right way to be able to revert this
      situation.

PMID- 10884542
TI  - Progress in gynecologic cancer detection and treatment.
AB  - Slow but steady progress has been made in the earlier diagnosis and better
      treatment of gynecological cancers, particularly over the last 50 years. Cervical
      cytology screening programs, where implemented, have led to a remarkable
      reduction in both the incidence and mortality from clinically invasive cervical
      cancer. This relatively simple technology has been truly one of the major success
      stories of modern medicine, but unfortunately this technique has not been
      uniformly applied to all women in the world, particularly to women in developing
      countries. New research into cervical cancer etiology, the role of HPV, and the
      development of vaccines against this virus offer a great hope particularly for
      developing countries. In addition, the combination of radiotherapy and
      chemotherapy has resulted in a marked improvement in outcome results for women
      with advanced cervical cancer. Ovarian cancer has seen the development of
      effective chemotherapy strategies for this disease. Currently this disease
      remains one of the major scourges in industrialized countries but the continued
      evolution of knowledge with regard to optimum sequencing of chemotherapeutic
      agents and surgery offers the prospect for better outcomes, less morbidity and a
      better quality of life. Ongoing research into the development of newer
      chemotherapeutic agents and a better understanding of the actual mechanisms
      regarding the efficacy of chemotherapy and drug resistance offers great promise
      for the future. Endoscopic surgery for staging and also for therapy shows promise
      for improved quality of life as well as outcomes for patients in the future and
      offers the challenge of trying to make this technology readily available to all
      women in the world. As we gain a better understanding of the molecular basis of
      disease and health we will truly be able to intervene in a preventive mode in the
      new millennium.

PMID- 10884543
TI  - Women's health: the unfinished agenda.
AB  - Improving women's health and nutrition could save millions of women in developing
      countries from needless suffering or premature death. Cost-effective health
      interventions exist to prevent this loss of lives. Complications of pregnancy and
      childbirth are the leading cause of death and disability among women of
      reproductive age in developing countries. Malnutrition is a major contributory
      factor to women's poor health and preventable mortality. Domestic violence,
      sexual abuse, and female genital mutilation carry a heavy physical and mental
      toll, as well as constitute an intolerable violation of human rights. Women's
      health is influenced by complex biological, social, and cultural factors that are
      highly interrelated. Significant progress can be achieved by strengthening and
      expanding an essential package of health services for women, improving the policy
      environment, and promoting more positive attitudes and behavior towards women's
      health.

PMID- 10884544
TI  - Smoking and women's health.
AB  - Each year more than 600000 women have deaths associated with cigarette smoking.
      In addition, cigarette smoking is associated with a wide array of morbidities
      (such as osteoporosis, cardiovascular disease, and adverse pregnancy outcomes).
      Two hundred million women smoke worldwide, and this number appears to be rising,
      particularly in developing countries. Obstetrician-gynecologists can play a role
      in reducing morbidity and mortality from cigarette smoking by educating women
      about the dangers, advising them not to smoke, and assisting those who do smoke
      to quit.

PMID- 10884545
TI  - A global overview of ethical issues in women's health.
AB  - The fundamental denial of basic human rights to reproductive choice, freedom from
      violence, and economic and educational development for women remains the major
      underpinning ethical issue in worldwide women's healthcare. The ability to choose
      when to have children, whether to have prenatal diagnosis or to make uncoerced
      choices at the end of life all hinge on the independence of each woman's ability
      to make choices about their own healthcare within the constraints of the health
      resources available to them. Technologic advances increase the complexity of
      assuring that the rights and best interest of the woman, the fetus or child, and
      society itself are balanced equitably in both the healthcare setting as well as
      the development of national or international policies and standards. The
      obstetrician/gynecologist, as an advocate for women's health worldwide, has an
      ethical obligation to assure human rights are extended to women and the
      obligation to assure that the care received is the best available.

PMID- 10884546
TI  - The role of FIGO in the advancement of women's health - in the year 2000.
AB  - The paper reviews the role and activities of FIGO as a global federation with a
      mission to promote the health and well-being of women and to improve the practice
      of gynecology and obstetrics.

PMID- 10884547
TI  - Rotary responds to women's health needs.
AB  - In working to improve the health of women, particularly in developing countries,
      governments face a monumental challenge. Limited resources, insufficient
      training, and poor infrastructure are just some of the obstacles to advancements
      in the field of female medicine. It is a goal of Rotary International, a
      worldwide association of service-minded business and professional people, to
      facilitate efforts to bring medical care to women and girls and to help them to
      build all-around healthy lives. This article gives background on Rotary
      International and highlights some of the ways Rotarians are using their
      resources, their global network, and their professional expertise to advance and
      promote women's health.

PMID- 10884548
TI  - Integrated approach to women's health.
AB  - The objective of this study was to demonstrate the importance of the practical
      application of the concept of reproductive health in Sao Paulo, Brazil, from 1991
      to 1998 at the Perola Byington Hospital with a new model of Primary Health Care
      (PHC) in which 2000 women/day, separated into two groups and over 45 years, was
      attended by nurses trained to detect the most frequently occurring gynecological
      problems supervised by doctors, who finalized the visit of each patient. The
      results demonstrated the advantages and viability of this strategy and also the
      bad health conditions of the women. Based on the high incidence of different kind
      of diseases detected, programs were set up for the diagnosis and treatment of
      gynecological cancer, STD, AIDS, hypertension, diabetes, etc. The results of two
      of these control programs, cervical cancer and breast cancer, demonstrated a
      significant increase in the diagnosis of early lesions. An economic study
      demonstrated an obvious and significant impact of this model not only in saving
      lives, but also in decreasing financial expenses in health.

PMID- 10884549
TI  - Changes in women's health in the Baltic republics of Lithuania, Latvia and
      Estonia during 1970-1997.
AB  - The rapid political, economic and social changes occurring in the Baltic
      republics of Estonia, Latvia and Lithuania fundamentally affect female health.
      Demographic trends, morbidity and mortality indicators point to a general decline
      in the status of women's health in the three Baltic republics since their
      independence from the Soviet Union. The transition period from socialist to
      market economy has clearly taken a toll in women's health. These have to be taken
      into consideration by health authorities in Lithuania, Latvia, Estonia as well as
      the European Union during the undergoing reforms being planned for healthcare
      systems in all EU countries in accession.

PMID- 10884550
TI  - Alcohols inhibit N-methyl-D-aspartate receptors via a site exposed to the
      extracellular environment.
AB  - N-Methyl-D-aspartate (NMDA) receptors are important CNS target sites of alcohols,
      but the site and mechanism of action of alcohols on NMDA receptors remains
      unclear. In CHO-K1 cells transfected with NR1/NR2B NMDA receptor subunits,
      ethanol inhibited NMDA-activated current with an IC(50) of 138 mM. Truncation of
      the intracellular C-terminal domain of the NR1 subunit (NR1T) did not alter
      ethanol sensitivity when combined with the NR2B subunit, but a similar truncation
      of the NR2B subunit (NR2BT) slightly enhanced ethanol sensitivity of receptors
      formed from coexpression with either NR1 or NR1T subunits. 1-Pentanol applied
      externally inhibited NMDA receptors with an IC(50) of 9.9 mM, but intracellular
      application of 1-pentanol (25 mM) did not alter NMDA receptor inhibition by
      externally applied ethanol or 1-pentanol. In addition, the amplitude of NMDA
      activated current did not decrease during the time required for 1-pentanol (25
      mM) to diffuse throughout the cytoplasm. Ethanol did not inhibit NMDA receptors
      when bath-applied in cell-attached patches or when applied to the cytoplasmic
      face of inside-out membrane patches. These results appear to be best explained by
      an action of alcohols on the NMDA receptor-channel protein, at a site located in
      a domain exposed to, or only accessible from, the extracellular environment.

PMID- 10884551
TI  - Group II, but not group I, metabotropic glutamate receptors in the rat nucleus
      accumbens contribute to amphetamine-induced locomotion.
AB  - Recently, it was reported that blocking metabotropic glutamate receptors (mGluRs)
      in the rat nucleus accumbens (NAcc) prevents the generation of locomotion by
      amphetamine (AMPH) in this site. In these studies, the non-selective group
      I/group II mGluR antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine [(R,S)
      MCPG] was used. The present study used more selective receptor antagonists to
      examine the specific contribution of group I and group II mGluRs to this effect.
      When co-injected bilaterally with AMPH into the NAcc, the group II selective
      mGluR antagonist (2S)-alpha-ethylglutamic acid [EGLU; 0.5-5.0 nmole/side] dose
      dependently blocked the locomotion and rearing produced by AMPH. Equimolar
      concentrations of the group I selective antagonist (R,S)-1-aminoindan-1,5
      dicarboxylic acid [AIDA; 0.5-5.0 nmole/side] were without effect. As previously
      reported for (R,S)-MCPG, neither of these receptor antagonists produced locomotor
      effects when injected alone in these concentrations into the NAcc. These results
      suggest that group II, but not group I, mGluRs in the rat NAcc contribute
      importantly to the ability of AMPH to produce locomotor activation.

PMID- 10884552
TI  - Characterization of [(3)H]-LY354740 binding to rat mGlu2 and mGlu3 receptors
      expressed in CHO cells using semliki forest virus vectors.
AB  - The binding properties of [(3)H]-LY354740 were characterized on rat metabotropic
      glutamate receptors mGlu2 and mGlu3 expressed in Chinese hamster ovary (CHO)
      cells using Semliki Forest virus vectors. The saturation isotherm gave K(D)
      values of 20+/-5 and 53+/-8 nM and B(max) values of 474+/-161 and 667+/-89
      fmol/mg protein for mGlu2 and mGlu3 receptors, respectively. NMDA, CaCl(2), DHPG
      and kainate were inactive up to 1 mM, whereas LY341495, DCG IV and ibotenate
      inhibited [(3)H]-LY354740 binding with similar potencies on both receptors. L-CCG
      I, L-AP4, L-AP5, LY354740 and 1S,3R-ACPD were 2- to 4-fold more potent inhibitors
      of [(3)H]-LY354740 binding to mGlu2 than mGlu3 receptors. However, MPPG and L-AP3
      had a 6-fold and DTT a 28-fold preference for mGlu2 over mGlu3. ZnCl(2), at 10
      mM, inhibited more than 70% of [(3)H]-LY354740 binding to mGlu2 receptors. At the
      same concentration it did not affect significantly [(3)H]-LY354740 binding to
      mGlu3 receptors. On the contrary, glutamate, quisqualate, EGLU and NAAG showed a
      3-, 5-, 7- and 12-fold preference for mGlu3 over mGlu2. Finally, GTPgammaS, which
      partially inhibited the binding on mGlu2 receptors, was inactive to inhibit
      [(3)H]-LY354740 binding on mGlu3 receptors.

PMID- 10884553
TI  - mu and delta-opioid receptor agonists induce mitogen-activated protein kinase
      (MAPK) activation in the absence of receptor internalization.
AB  - Agonist-promoted internalization (endocytosis) of G-protein-coupled receptors
      (GPCRs), including all three opioid receptor types (mu, delta and kappa), has
      been shown to occur via the clathrin endosomal pathway in response to receptor
      phosphorylation and the actions of the proteins, beta-arrestin and dynamin. Many
      members of the GPCR family stimulate mitogen-activated protein kinases (MAPK or
      ERK) activity and, in several cases, it appears that MAPK activation is dependent
      on receptor internalization. We have reinvestigated the question of whether
      internalization is obligatory for MAPK activation by opioid receptors, using cell
      lines expressing the cloned mu or delta receptor. Morphine, which is known to
      activate both mu and delta receptors, does not induce their rapid internalization
      into clathrin-coated endosomes. However, morphine produced a robust stimulation
      of MAPK in both cell lines, as demonstrated by the appearance of phosphorylated
      MAPK. Moreover, pre-exposure of cells to the internalization inhibitors,
      concanavalin A or hypertonic sucrose, totally blocked DAMGO mu-selective agonist)
      and DTLET (delta-selective agonist)-mediated receptor internalization, yet
      neither treatment affected MAPK phosphorylation induced by these peptides. Our
      results provide evidence that receptor internalization is not an obligatory
      requirement for MAPK activation by mu and delta opioid receptors. Hypotheses are
      presented to explain the seemingly contradictory results obtained from different
      laboratories.

PMID- 10884554
TI  - Adaptive changes in M1 muscarinic receptors localized to specific rostral brain
      regions during and after morphine withdrawal.
AB  - Morphine-dependent rats were allowed to undergo withdrawal by abrupt
      discontinuation of the drug. The regional expression of brain M1 muscarinic
      receptors was measured directly by autoradiographic determination with [(3)H]
      pirenzepine, and indirectly by quantifying the relative levels of M1 mRNA
      encoding the receptor protein. Patterns of receptor changes after morphine
      treatment were in general agreement using the two methods. Frontal cortical
      samples derived from morphine-dependent rats exhibited a 28% increase in M1
      receptor mRNA measured at the end of the infusion. At the peak of the withdrawal,
      M1 mRNA levels for dependent rats were much lower (33.4%) than those for control
      rats. Hippocampal samples derived from morphine-dependent rats exhibited no
      changes in M1 mRNA levels after the morphine infusion. During the peak of
      withdrawal, however, hippocampal M1 mRNA levels were reduced (57%) compared with
      levels for controls. The M1 mRNA levels remained at this reduced degree of
      expression even after withdrawal symptoms had subsided. Addition of
      diisopropylflurophophate (DFP) to the morphine infusion schedule inhibited the
      adaptive changes in M1 mRNA levels induced by morphine. During the peak period of
      withdrawal, M1 mRNA levels in the hippocampus declined by only 18% as compared
      with 57% for the morphine control group. The adaptive decrease in hippocampal M1
      receptors after withdrawal subsided may reflect prolonged heightened cholinergic
      activity in an area where such cholinergic innervation plays an important role in
      memory.

PMID- 10884555
TI  - Pharmacologic reversal of pertussis toxin-induced thermal allodynia in mice.
AB  - We have previously demonstrated that the intrathecal administration of pertussis
      toxin produces a long-lasting thermal allodynia in mice. The purpose of the
      present studies was to compare the antinociceptive and the antiallodynic effects
      of drugs that are commonly used in treating neuropathic allodynia in untreated
      mice and in mice which had been administered vehicle or pertussis toxin
      intrathecally 7 days previously. In untreated mice, morphine, fentanyl,
      clonidine, oxymetazoline, desipramine and lidocaine, but not MK801, produced dose
      related antinociception when tested using a 55 degrees C water tail-flick test.
      However, 7 days after the intrathecal injection of pertussis toxin, which induced
      a condition of thermal allodynia when tested using a 45 degrees C water bath, the
      full opioid and the full alpha(2)-adrenergic receptor agonists fentanyl and
      clonidine, but not the partial opioid nor the partial alpha(2)-adrenergic
      receptor agonists morphine and oxymetazoline, reversed the pertussis toxin
      induced thermal allodynia. Moreover, lidocaine, desipramine, carbamazepine and
      MK801 failed to reverse the pertussis toxin-induced thermal allodynia. The
      present results suggest that decrements in G(i)/G(o)-protein function may be
      involved in initiating and/or maintaining some neuropathic pain states. Moreover,
      the results of the present study suggest that the use of full, but not partial,
      opioid or alpha(2)-agonists may be useful in the treatment of thermal allodynic
      pain states which may be due at least in part to inhibitory second messenger
      system dysfunction. Further, the underlying biochemistry of the apparent
      allodynic pain state induced by intrathecal administration of pertussis toxin
      warrants further investigation.

PMID- 10884556
TI  - Overlapping selectivity of neurotoxin and dihydropyridine calcium channel
      blockers in cerebellar granule neurones.
AB  - Calcium (Ca(2+)) currents have been studied extensively in cerebellar granule
      neurones, but much of the whole-cell pharmacology is inconsistent. Ca(2+) channel
      currents were recorded from granule neurones to investigate whether the commonly
      used Ca(2+) channel blockers show overlapping selectivity. Using combinations of
      toxin channel blockers, 45% of the total current was shown to be carried by
      Ca(2+) channels susceptible to block by the combined, or cumulative application
      of, omega-agatoxin IVA, omega-conotoxin GVIA and omega-conotoxin MVIIC, thus
      representing P/Q- and N-type channel currents. However, sequential application of
      these toxins showed that substantial overlap occurred in the proportions of
      current sensitive to individual toxins. Application of the 1, 4-dihydropyridine
      nicardipine at 1 microM, a concentration reported to be selective for L-type
      channels, blocked 16% of the total current, without reducing the current
      sensitive to the toxins used. However, greater concentrations of nicardipine (>10
      microM) blocked a proportion of the total current that could not be accounted for
      by L-type channels alone. These results demonstrate that a pharmacological
      approach based on the L, N, P/Q, and R classification does not adequately
      describe the Ca(2+) channel subtypes found in cerebellar granule neurones due to
      substantial cross-selectivity to the drugs and toxins used.

PMID- 10884557
TI  - Inhibition of neuronal high-voltage activated calcium channels by the omega
      phoneutria nigriventer Tx3-3 peptide toxin.
AB  - We have investigated the effect of omega-PnTx3-3 (referred to in previous papers
      simply as Tx3-3), a peptide toxin from the venom of the spider Phoneutria
      nigriventer, on neuronal high-voltage activated (HVA) Ca(2+) channels, using
      whole-cell patch-clamp. omega-PnTx3-3 (120 nM) blocked 74+/-8% of the total HVA
      Ca(2+) currents of cerebellar granule neurones, without affecting the low-voltage
      activated (LVA) current. P/Q/R-type currents in cerebellar granule neurones,
      isolated using 4 microM nicardipine and 100 nM omega-conotoxin GVIA, were
      markedly (79+/-6%) inhibited by 60 nM omega-PnTx3-3. R-type currents, isolated
      either by additional application of 0.5-1 microM of omega-agatoxin IVA or by pre
      incubation with 5 microM omega-conotoxin MVIIC were inhibited almost totally by
      120 nM of omega-PnTx3-3. omega-PnTx3-3 reversibly altered the kinetics of the
      P/Q/R current, increasing the degree of inactivation that occurred during a 50 ms
      pulse from 20% to 40%. N-type currents, recorded from neuroblastoma N18 cells,
      were partially (34+/-2%) inhibited by 320 nM omega-PnTx3-3. L-type currents,
      recorded from GH3 cells, were partially (45+/-12%) inhibited by 80 nM omega-PnTx3
      3. We conclude that omega-PnTx3-3 inhibits all known HVA Ca(2+) channels, and
      most effectively the P/Q- and R-type currents.

PMID- 10884558
TI  - Purinergic and muscarinic receptor activation activates a common calcium entry
      pathway in rat neocortical neurons and glial cells.
AB  - The nature of metabotropic purinergic and muscarinic receptor-mediated increases
      in intracellular calcium in primary rat neocortical neurons and glial cells has
      been investigated using fluorescence imaging techniques. Bath-application of ATP
      and muscarine (10 microM) elicited a characteristic increase in intracellular
      calcium in both neurons and glial cells. The profile of this response consisted
      of an initial transient increase followed by a sustained elevation (the plateau
      phase) which was dependent on extracellular calcium. Examination of the
      pharmacological basis of the purinergic receptor-mediated calcium response using
      10 microM 2-methyl-thio ATP (MeS-ATP) and UTP revealed that P(2Y) receptor
      activation underlies this response. The calcium influx pathway responsible for
      the sustained calcium response was inhibited by metal ions. In both cell types
      La(3+) and Zn(2+) (100 microM) effectively inhibited the plateau phase of the
      response, whilst 100 microM Ni(2+) had little or no effect. In conclusion, P(2Y)
      purinergic and muscarinic receptor activation evoke a sustained increase in
      intracellular calcium in neocortical neurons and glial cells. This response has
      similar characteristics to that we have previously described following mGlu(5)
      activation. We propose that in these cell types stimulation of metabotropic
      receptors coupled to phosphoinositide turnover activates a common calcium entry
      pathway that is distinct from voltage-gated calcium channels and resembles store
      operated calcium entry.

PMID- 10884559
TI  - Inhibition of different pathways influencing Na(+) homeostasis protects
      organotypic hippocampal slice cultures from hypoxic/hypoglycemic injury.
AB  - A prominent feature of cerebral ischemia is the excessive intracellular
      accumulation of both Na(+) and Ca(2+), which results in subsequent cell death. A
      large number of studies have focused on pathways involved in the increase of the
      intracellular Ca(2+) concentration [Ca(2+)](i), whereas the elevation of
      intracellular Na(+) has received less attention. In the present study we
      investigated the effects of inhibitors of different Na(+) channels and of the
      Na(+)/Ca(2+) exchanger, which couples the Na(+) to the Ca(2+) gradient, on
      ischemic damage in organotypic hippocampal slice cultures. The synaptically
      evoked population spike in the CA1 region was taken as a functional measure of
      neuronal integrity. Neuronal cell death was assessed by propidium iodide
      staining. The Na(+) channel blocker tetrodotoxin, and the NMDA receptor blocker
      MK 801, but not the AMPA/kainate receptor blocker NBQX prevented ischemic cell
      death. The novel Na(+)/Ca(2+) exchange inhibitor 2-[2-[4-(4
      nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate (KB-R7943), which
      preferentially acts on the reverse mode of the exchanger, leading to Ca(2+)
      accumulation, also reduced neuronal damage. At higher concentrations, KB-R7943
      also inhibits Ca(2+) extrusion by the forward mode of the exchanger and
      exaggerates neuronal cell death. Neuroprotection by KB-R7943 may be due to
      reducing the [Ca(2+)](i) increase caused by the exchanger.

PMID- 10884560
TI  - The mechanism of actions of 3-(5'-(hydroxymethyl-2'-furyl)-1-benzyl indazole (YC
      1) on Ca(2+)-activated K(+) currents in GH(3) lactotrophs.
AB  - The effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1), an
      activator of soluble guanylyl cyclase, on ionic currents have been assessed in
      rat pituitary GH(3) lactotrophs. In GH(3) cells bathed in normal Tyrode's
      solution, YC-1 (1 microM) reversibly suppressed the amplitude of the Ca(2+)
      activated K(+) current (I(K(Ca))). YC-1 at a concentration above 10 microM
      produced a biphasic response in the amplitude of I(K(Ca)), i.e., an initial
      decrease followed by a sustained increase. When the pipette solutions were filled
      with high EGTA (10 mM), the YC-1-induced stimulatory effect on I(K(Ca)) was
      abolished. Over a similar concentration range, YC-1 also effectively inhibited
      the voltage-dependent K(+) current (I(K(V))) in GH(3) cells. The IC(50) value
      required for the inhibition of I(K(V)) by YC-1 was 1 microM. Unlike YC-1, 8-bromo
      cGMP did not inhibit I(K(Ca)). However, YC-1 (10 microM) did not affect the
      amplitude of L-type Ca(2+) current. In the cell-attached configuration,
      application of YC-1 (10 microM) to the bath did not change the single-channel
      conductance of the large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels;
      however, it did increase the opening probability of BK(Ca) channels. In contrast,
      in the outside-out configuration, YC-1 (10 microM) significantly suppressed the
      opening probability of BK(Ca) channels. The present study shows dual effects of
      YC-1 on I(K(Ca)) in GH(3) cells. The YC-1-mediated stimulation of I(K(Ca)) may
      result from elevated cytosolic Ca(2+), whereas the inhibition of I(K(Ca)) and
      I(K(V)) by YC-1 appears to be direct and independent of the activation of soluble
      guanylyl cyclase. Caution thus needs to be used in attributing the YC-1-mediated
      response to the activation of soluble guanylyl cyclase.

PMID- 10884561
TI  - Effects of sustained administration of the serotonin and norepinephrine reuptake
      inhibitor venlafaxine: I. in vivo electrophysiological studies in the rat.
AB  - The effect of a 21-day treatment with the dual 5-HT and NE reuptake blocker
      venlafaxine (delivered s.c. by osmotic minipumps) was assessed on the time
      required for a 50% recovery (RT(50)) of the firing activity of dorsal hippocampus
      CA(3) pyramidal neurons from the suppression induced by microiontophoretic
      applications of 5-HT and NE. The RT(50) values for 5-HT were increased by both 10
      and 40 mg/kg/day regimens of venlafaxine, whereas those for NE were increased
      only by the 40 mg/kg/day regimen, indicative of a greater potency of venlafaxine
      in blocking 5-HT reuptake. The sensitivity of the postsynaptic 5-HT(1A) and
      alpha(2)-adrenergic receptors was altered by neither regimen of venlafaxine.
      Using a paradigm by which the 5-HT(1A) antagonist WAY 100635 can induce a
      disinhibition of firing activity of CA(3) pyramidal neurons, it was demonstrated
      that the high, but not the low, dose of venlafaxine led to an enhanced tonic
      activation of postsynaptic 5-HT(1A) receptors in the dorsal hippocampus. The
      duration of the suppressant effect of the firing activity of CA(3) hippocampus
      pyramidal neurons produced by the electrical stimulation of the ascending 5-HT
      pathway was significantly reduced when the frequency of the stimulation was
      enhanced from 1 Hz to 5 Hz in control rats and in rats treated with 10 mg/kg/day,
      but not with 40 mg/kg/day of venlafaxine. Hence, venlafaxine induced a
      desensitization of the terminal 5-HT(1B) autoreceptor only at the high dose. A 2
      day treatment with 10 mg/kg/day of venlafaxine induced a suppression of the
      firing activity of 5-HT neurons of the dorsal raphe. The firing activity of these
      neurons was back to control level in rats that had been treated for 21 days with
      the same dose of venlafaxine. The suppressant effect of the i.v. administration
      of the 5-HT autoreceptor agonist LSD on the firing activity of dorsal raphe 5-HT
      neurons was reduced in rats that had been treated for 21 days with 10 mg/kg/day
      of venlafaxine. A 2-day treatment with 40 mg/kg/day of venlafaxine, unlike the 10
      mg/kg/day regimen, induced a marked suppression of the firing activity of locus
      coeruleus NE neurons. However, in contrast to 5-HT neurons, NE neurons did not
      recover their firing activity after a 21-day treatment. Taken together, the
      results from this study indicate that the low dose of venlafaxine blocked
      selectively the reuptake of 5-HT, whereas the high dose blocked the reuptake of
      both 5-HT and NE. Moreover, an enhancement of serotonergic neurotransmission by
      venlafaxine was only achieved under conditions whereby the desensitization of the
      terminal 5-HT(1B) autoreceptor is appended to that of the somatodendritic 5
      HT(1A) receptor.

PMID- 10884563
TI  - Estrogen desensitizes 5-HT(1A) receptors and reduces levels of G(z), G(i1) and
      G(i3) proteins in the hypothalamus.
AB  - The present study investigated whether estrogen would desensitize hypothalamic
      serotonin(1A) (5-HT(1A)) receptors by examining the neuroendocrine response to 8
      OH-DPAT, a 5-HT(1A) agonist. Rats were ovariectomized, allowed to recover for 5
      days, then given 2 daily injections of estradiol benzoate or vehicle (10
      microg/day, s.c.). Twenty-four hours after the second injection, rats were
      challenged with a sub-maximal dose of 8-OH-DPAT (50 microg/kg, sc) or saline 15
      min prior to sacrifice. 8-OH-DPAT produced a significant increase in plasma
      oxytocin, ACTH and corticosterone levels in ovariectomized rats. While estrogen
      treatment for 2 days did not alter basal hormone levels, it did significantly
      reduce the magnitude of oxytocin, ACTH and corticosterone responses to 8-OH-DPAT.
      The reduction in hormone responses was accompanied by a significant reduction in
      hypothalamic levels of G(z), G(i1) and G(i3) proteins (by 50%, 30% and 50%,
      respectively). These findings suggest that a reduction in these G proteins may
      contribute to the mechanisms underlying estrogen-induced desensitization of 5
      HT(1A) receptors. The desensitization of 5-HT(1A) receptors has been suggested to
      underlie the therapeutic effects of antidepressant 5-HT uptake inhibitors
      (SSRIs). Thus, the present results suggest that estrogen or estrogen-like
      substances in combination with SSRIs may prove effective in developing novel
      therapeutic strategies for neuropsychiatric disorders in women.

PMID- 10884562
TI  - Effects of sustained administration of the serotonin and norepinephrine reuptake
      inhibitor venlafaxine: II. In vitro studies in the rat.
AB  - The effects of long-term administrations of a low (10 mg/kg/day) and a high (40
      mg/kg/day) dose of the dual 5-HT and NE reuptake inhibitor venlafaxine (delivered
      s.c. by osmotic minipumps for 21 days) were assessed on the electrically-evoked
      release of tritium from hippocampal slices preloaded with either [(3)H]5-HT or
      [(3)H]NE, 48 h after the removal of the minipump. The high, but not the low, dose
      regimen of venlafaxine enhanced the electrically-evoked release of [(3)H]5-HT
      while treatment with the high dose of venlafaxine failed to alter the
      electrically-evoked release of [(3)H]NE. The inhibitory effect of the 5-HT(1B)
      agonist CP 93,129 on the electrically evoked release of [(3)H]5-HT was unaltered
      by the low dose regimen of venlafaxine while it was attenuated in rats treated
      with the high dose of venlafaxine, indicative of a functional desensitization of
      the terminal 5-HT(1B) autoreceptor. Unexpectedly, neither regimen of venlafaxine
      altered the inhibitory effect of UK 14,304 on the electrically evoked release of
      both [(3)H]5-HT and [(3)H]NE, indicating that neither the alpha(2)-adrenergic
      auto- nor heteroreceptors were desensitized. Finally, the functions of the 5-HT
      and NE reuptake process were assessed. None of the treatment regimens altered the
      basal uptake of [(3)H]5-HT from hippocampal or mesencephalic slices nor that of
      [(3)H]NE from hippocampal slices. Finally, the enhancing effect of 1 microM of
      paroxetine in the perfusion medium on the electrical release of [(3)H]5-HT was
      unaltered in hippocampal slices prepared from rats that had been treated for 21
      days with 40 mg/kg/day of venlafaxine. Taken together, these results indicate
      that, in terms of alteration of the sensitivity of the terminal 5-HT(1B)
      autoreceptor, alpha(2)-adrenergic auto-and heteroreceptors, the effects of long
      term administration of venlafaxine are no different than those observed with
      classical SSRI's.

PMID- 10884564
TI  - 5-HT(1A) and 5-HT(1B/1D) receptors are involved in the modulation of the
      trigeminovascular system of the cat: a microiontophoretic study.
AB  - Electrical stimulation of the superior sagittal sinus in the cat activated
      neurones in the trigeminal nucleus caudalis. The mean latency of these responses
      (10.1 ms) was consistent with activation of Adelta-fibres. Microiontophoretic
      ejection of either the selective serotonin(1A) (5-HT(1A)) agonist (+)8-OH-DPAT or
      the 5-HT(1B/1D) agonist alniditan resulted in the reversible suppression of the
      response to superior sagittal sinus stimulation of 29/46 and 18/20 trigeminal
      neurones, respectively. The response to sagittal sinus stimulation was suppressed
      by 39+/-5% (n=46) by (+)8-OH-DPAT and 65+/-5% (n=20) by alniditan.
      Microiontophoretic ejection of the selective 5-HT(1A) receptor antagonist WAY
      100635 significantly antagonised the effect of (+)8-OH-DPAT (effect reduced by
      30%, P<0.05). The ejection of GR-127935, a selective 5-HT(1B/1D), antagonist,
      significantly antagonised the effect of alniditan (effect reduced by 52%,
      P<0.02). In eight neurones the response to convergent facial receptive field
      stimulation was also tested in the presence of alniditan. Only 4/8 receptive
      field responses were suppressed by alniditan (compared to 8/8 sagittal sinus
      responses) and alniditan had significantly less quantitative effect on the
      response to receptive field stimulation than on the response to sagittal sinus
      stimulation in the same neurones (mean reduction 36+/-14% and 66+/-8%,
      respectively, P<0.05). These results suggest that pharmacological modulation of
      the trigeminovascular system can occur at the first central synapse and that, in
      addition to 5-HT(1B/1D) receptors, 5-HT(1A) receptors may be involved in the
      modulation of sensory neurotransmission in the trigeminovascular system.

PMID- 10884565
TI  - The effects of compounds varying in selectivity as 5-HT(1A) receptor antagonists
      in three rat models of anxiety.
AB  - Compounds varying in selectivity as 5-HT(1A) receptor antagonists have recently
      been reported to produce benzodiazepine-like antianxiety effects in mice. To
      assess the cross-species generality of these findings, the present experiments
      compared the effects of diazepam (0.625-5 mg/kg) with those of several non
      selective (MM-77, 0.03-1 mg/kg and pindobind-5-HT(1A), 0.1-5 mg/kg) and selective
      (WAY100635, 0.01-10 mg/kg, p-MPPI, 0.01-3 mg/kg and SL88.0338, 0.3-10 mg/kg) 5
      HT(1A) receptor antagonists in three well-validated anxiolytic screening tests in
      rats: punished lever-pressing, punished drinking, and the elevated plus-maze. In
      the punished lever-pressing conflict test, none of the 5-HT(1A) receptor
      antagonists modified rates of punished responding, whereas in the punished
      drinking test, WAY100635 (0.3-1 mg/kg), SL88.0338 (3-10 mg/kg), p-MPPI (1 mg/kg),
      MM-77 (0.03-0.3 mg/kg), but not pindobind-5-HT(1A), produced clear anticonflict
      activity. However, the increase in punished responding with the 5-HT(1A)
      compounds was smaller than that produced by diazepam, indicating weaker
      anxiolytic-like activity. In the elevated plus-maze test, WAY100635 (0.1-0.3
      mg/kg), SL88.0338 (0.3-10 mg/kg), MM-77 (0.01-3 mg/kg), pindobind-5-HT(1A) (0.1-3
      mg/kg), but not p-MPPI, showed anxiolytic-like activity on traditional behavioral
      indices, increasing the percentage of time spent in open arms and the percentage
      of open arm entries. As was the case in the punished drinking test, the magnitude
      of the positive effects of the 5-HT(1A) compounds was generally smaller than that
      of diazepam. Of the ethological measures recorded in the plus-maze, all compounds
      markedly decreased risk assessment (i.e. attempts) over the entire dose-range,
      but only diazepam clearly increased directed exploration (i.e. head-dipping).
      Although the present results demonstrate that 5-HT(1A) receptor antagonists
      elicit anxiolytic-like effects in rats, this action appears to be test-specific
      and, unlike previous findings in mice, smaller than that observed with
      benzodiazepines. The data are discussed in relation to the possible relevance of
      species differences in 5-HT(1A) receptor function and the nature of the anxiety
      response studied.

PMID- 10884566
TI  - The influence of the benzodiazepine receptor antagonist flumazenil on the
      anxiolytic-like effects of CGP 37849 and ACPC in rats.
AB  - In this paper we examined the effect of flumazenil (Ro 15-1788, 10 mg/kg), a
      benzodiazepine receptor antagonist, on the anticonflict activity of DL-(E)-2
      amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849), a competitive N-methyl-D
      aspartate (NMDA) receptor antagonist, and 1-aminocyclopropanecarboxylic acid
      (ACPC), a partial agonist at glycine(B) receptors, in the Vogel conflict drinking
      test in rats. The effect of flumazenil on the anxiolytic-like (in the plus-maze
      test) and the anticonvulsant (in the maximal electroshock-induced seizures)
      activities of CGP 37849 in rats was also studied. Diazepam was used as a
      reference drug. CGP 37849 (2. 5-5 mg/kg), ACPC (50-200 mg/kg) and diazepam (2.5-5
      mg/kg) significantly and dose-dependently increased the number of shocks accepted
      during experimental sessions in the conflict drinking test. Flumazenil partly but
      significantly reduced the anticonflict effect of CGP 37849, and it fully blocked
      the anticonflict effect of ACPC and diazepam. CGP 37849 (2.5-5 mg/kg) and
      diazepam (2.5-5 mg/kg) were also active in the plus-maze test, as they
      significantly increased the percentage of the time spent in and entries into the
      open arms of the plus-maze, both those effects having been antagonized by
      flumazenil. Flumazenil alone was inactive in both the conflict drinking and the
      plus-maze tests. In the maximal electroshock-induced seizures, both CGP 37849
      (2.5-5 mg/kg) and diazepam (5-10 mg/kg) produced anticonvulsant effects, of which
      only that of diazepam was antagonized by flumazenil. The results of the present
      study showing antagonism of flumazenil towards the anxiolytic-like effects of CGP
      37849 and ACPC suggest involvement of benzodiazepine receptors in such an
      activity of the NMDA and glycine(B) receptor ligands, respectively, which may be
      due to a possible interaction between NMDA and GABA/benzodiazepine systems. The
      lack of effect of the benzodiazepine antagonist on the anticonvulsant activity of
      CGP 37849 indicates that involvement of benzodiazepine receptors in the
      pharmacological action of the NMDA antagonist is not a general phenomenon.

PMID- 10884567
TI  - Anxiolytic-like properties of melatonin receptor agonists in mice: involvement of
      mt1 and/or MT2 receptors in the regulation of emotional responsiveness.
AB  - The anxiolytic-like properties of melatonin have been established in rodents. The
      present study investigated the possible involvement of melatonin
      receptors/binding sites in the regulation of emotional responsiveness in mice,
      using an mt1/MT2 receptor specific agonist (S 23478) and two specific ligands of
      MT3 binding sites with agonistic properties (N-acetylserotonin (NAS) and 5
      methoxycarbonylamino N-acetyltryptamine (5-MCA-NAT)). We examined the behavioural
      effects of these compounds in C3H/He mice confronted with two anxiety models: the
      free-exploratory test, in which C3H/He mice present neophobic reactions ("trait"
      anxiety), and the light/dark choice test, which is an unconditioned conflict test
      (inducing "state" anxiety). Melatonin and S 23478 decreased anxious reactions in
      both the free-exploratory test (5-25 mg/kg) and the light/dark choice test
      (melatonin: 20 mg/kg; S 23478: 10-20-40 mg/kg). NAS exerted anxiolytic-like
      effects only at a dose of 35 mg/kg in the free-exploratory test and at a dose of
      40 mg/kg in the light/dark choice test. Finally, 5-MCA-NAT was devoid of
      anxiolytic-like effects in both tests. These results suggest that the anxiolytic
      properties of melatonin could involve the activation of mt1 and/or MT2 receptors
      rather than of the MT3 binding site.

PMID- 10884568
TI  - Impaired leptin signal transduction with age-related obesity.
AB  - Leptin contributes to the regulation of both food intake and energy expenditure.
      We previously demonstrated that the F-344xBN rat, a rodent model for late-onset
      obesity, is leptin resistant, suggesting that leptin signal transduction may be
      impaired in these aged, overweight rats. To test this hypothesis, we examined the
      in vivo dose-response and time-course response of leptin-induced STAT3 activation
      (phosphorylation and binding activity to the SIE M67 oligonucleotide) in the
      hypothalamus of young rats along with the dose-response leptin-induced STAT3
      phosphorylation (P-STAT3) and maximum increase in binding activity in young and
      aged rats. In young rats there was a dose (0-1 mg, iv) and time dependent
      increase in P-STAT3 and in P-STAT3 binding activity. P-STAT3 paralleled the rise
      and fall in serum leptin levels with P-STAT3 elevated for at least 4 h with
      return to basal levels by 14 h after 1 mg leptin. The maximum level of leptin
      induced P-STAT3 was unchanged with age, but the dose for half maximal
      phosphorylation was greater in aged (138 microg) compared with young (26 microg)
      rats. In addition, the leptin-induced increase in P-STAT3 transcription factor
      binding was diminished in aged rats. These data suggest that leptin signal
      transduction, in vivo, demonstrate a time and dose response increase paralleling
      the rise and fall in serum leptin, suggesting that serum leptin levels are the
      most important factor in determining leptin-induced phosphorylation of STAT3 in
      the hypothalamus. In addition, aged, overweight rats demonstrate reduced signal
      transduction in response to leptin, with reduced sensitivity for STAT3
      phosphorylation and diminished leptin-induced P-STAT3 transcription factor
      binding. This impaired leptin signal transduction may be due to either the
      elevated obesity with age or due to age itself or both.

PMID- 10884569
TI  - Evidence for a role of endogenous neurotensin in the initiation of amphetamine
      sensitization.
AB  - This study was aimed at testing the hypothesis that endogenous neurotensin plays
      a role in the initiation of sensitization to the locomotor activating effect of
      amphetamine. During an initial training phase, different groups of male rats were
      injected on four occasions (every second day: Days 1, 3, 5 and 7) with one of
      three doses (40, 80 or 160 microg/kg, ip) of the neurotensin antagonist, SR
      48692, or its vehicle, followed 30 min later by amphetamine (1.5 mg/kg, ip), or
      saline. Ambulatory, non-ambulatory, and vertical movements were measured for 2 h
      in photocell cages immediately following the second injection. One week after the
      training phase, sensitivity to amphetamine (0.75 mg/kg, ip) was tested in all the
      rats (sensitization test). The results show that SR-48692, when given alone,
      produced levels of locomotor activity that were not statistically different from
      control. At the low dose, it potentiated amphetamine-induced ambulatory and non
      ambulatory movements, an effect observed on Day 7 but not on Day 1. On the day of
      the sensitization test, rats pre-exposed to amphetamine alone displayed stronger
      ambulatory and non-ambulatory movements than vehicle pre-exposed rats, a
      sensitization effect that was attenuated and prevented by SR-48692 at 80 and 160
      microg/kg, respectively. The present results demonstrate that activation of
      neurotensin receptors by endogenous neurotensin is required for the initiation of
      amphetamine sensitization. They provide additional evidence that an increase in
      central neurotensinergic neurotransmission may lead to a lasting increased
      sensitivity to psychostimulant drugs.

PMID- 10884570
TI  - The new antiepileptic drugs lamotrigine and felbamate are effective in phenytoin
      resistant kindled rats.
AB  - We evaluated the anticonvulsant efficacy of the antiepileptic drugs (AEDs)
      lamotrigine (LTG) and felbamate (FBM) in amygdala kindled rats that had been
      preselected with respect to their response to phenytoin. Anticonvulsant response
      was tested by determining the afterdischarge threshold (ADT), i.e., a sensitive
      measure for drug effects on focal seizure activity. By repeated testing with the
      phenytoin prodrug fosphenytoin, 3 groups of kindled rats were separated: rats in
      which consistent anticonvulsant effects were obtained (phenytoin responders),
      rats which showed no anticonvulsant response (phenytoin nonresponders), and rats
      with variable responses (variable phenytoin responders). The latter, largest
      group was used to evaluate at which doses LTG and FBM exerted significant
      anticonvulsant effects on ADT 1 h after i.p. drug administration. Effective doses
      were then used for drug testing in phenytoin responders and nonresponders. Both
      LTG and FBM proved to be effective anticonvulsant drugs in the kindling model by
      markedly increasing the ADT. Seizure severity and duration recorded at ADT
      currents were hardly reduced, indicating that both drugs predominantly affect
      induction of focal seizures and not seizure spread from the focus. In phenytoin
      nonresponders, LTG and FBM significantly increased ADT, which is in line with
      their proven efficacy in patients with refractory partial epilepsy in whom
      phenytoin has failed. However, LTG and, more markedly, FBM were clearly more
      efficacious in increasing ADT in phenytoin responders than in nonresponders,
      substantiating that the difference in phenytoin response between these groups of
      kindled rats extends to other AEDs. The data in this study reveal that phenytoin
      nonresponders are a unique model for the search for new AEDs with improved
      efficacy in refractory partial epilepsy.

PMID- 10884571
TI  - Imidazoline I(2)-receptors and spinal reflexes in the decerebrated rabbit.
AB  - Idazoxan potentiates spinal reflexes in the decerebrated rabbit, an effect that
      has been attributed to antagonism of tonic noradrenergic inhibition. It is now
      known that this drug has a higher affinity for I(2)-imidazoline receptors than
      alpha(2)-receptors. The roles of I(2)-receptors in modulating transmission in
      spinal reflex pathways have been investigated using the selective ligands RX
      821029 and RS-45041-190, and, as I(2)-receptors are closely associated with
      monoamine oxidase (MAO), the MAO inhibitors pargyline and clorgyline. In
      decerebrated rabbits with an intact spinal cord, intrathecal doses of 5-365
      microg (cumulative) of the I(2)-ligands augmented, to 150-180% of pre-drug
      levels, the reflex responses of medial gastrocnemius motoneurones to electrical
      stimulation of the sural nerve, and significantly increased mean arterial blood
      pressure by approximately 10 mmHg over pre-drug values. Neither MAO inhibitor had
      significant effects on reflexes, but the highest dose of the MAO-A selective
      agent clorgyline (365 microg cumulative) caused a significant rise in blood
      pressure of 6 mmHg. Neither the I(2)-ligands nor the MAO inhibitors prevented the
      further enhancement of reflexes or blood pressure by subsequent administration of
      the selective alpha(2)-adrenoceptor antagonist RX 821002. In decerebrated,
      spinalized rabbits, intrathecal RS-45041-190 (60 microg, single dose) increased
      spinal reflex responses to 109% of pre-drug values, a significantly smaller
      effect than that seen in non-spinal preparations, and had no effect on blood
      pressure. These data show that imidazoline I(2)-receptors can influence somatic
      and autonomic motor outflows. These effects should be taken into account when
      interpreting the spinal effects of imidazoline-based adrenoceptor-active drugs.

PMID- 10884572
TI  - Rapamycin, but not FK506 and GPI-1046, increases neurite outgrowth in PC12 cells
      by inhibiting cell cycle progression.
AB  - Immunophilin ligands such as rapamycin, FK506 and GPI-1046 have been reported to
      increase neurite outgrowth in vitro and to have neuroprotective activity in vitro
      and in vivo. In this study, however, FK506 and GPI-1046 (0.1-1000 nM) had little
      effect on neurite outgrowth in PC12 cells in either the presence or absence of
      nerve growth factor. In contrast, rapamycin markedly increased neurite outgrowth
      in PC12 cells in the presence of a low concentration of nerve growth factor
      (EC(50)=10 nM). Unlike FK506 and GPI-1046, rapamycin is an inhibitor of cell
      cycle progression. Other cell cycle inhibitors such as ciclopirox and
      flavopiridol also increased neurite outgrowth in PC12 cells in the presence of a
      low concentration of nerve growth factor (EC(50)=250 nM and 100 nM,
      respectively). The neuroprotective effects of FK506, rapamycin and GPI-1046 were
      also tested in a rodent model of permanent focal cerebral ischemia. FK506 and
      rapamycin decreased infarct volume by 40% and 37%, respectively, whereas GPI-1046
      was ineffective. These data do not support the previous suggestion that FK506 and
      GPI-1046 increase neurite outgrowth of PC12 cells in vitro. Rapamycin increases
      neurite outgrowth of PC12 cells, an effect that can be ascribed to its ability to
      inhibit cell cycle progression. The neuroprotective effect of FK506 and rapamycin
      against cerebral ischemia is probably not due to differentiation of neuronal
      precursors or stimulation of neuronal regeneration.

PMID- 10884573
TI  - Rapamycin and FK506 induce long-term potentiation by pairing stimulation via an
      intracellular Ca(2+) signaling mechanism in rat hippocampal CA1 neurons.
AB  - Immunophilin-CsA and -FK506 complexes bind to calcineurin (CaN) and inhibit its
      phosphatase activity leading to enhancement of neuronal activities. However,
      inhibition of CaN activity is not the mediator of modulatory activity for IP3 and
      ryanodine receptors and does not mediate the neurotrophic actions of FK506. FK506
      binding protein (FKBP)-12 also binds rapamycin, another immunosuppressant which
      does not affect CaN activity. Using whole-cell patch clamp techniques, excitatory
      postsynaptic currents (EPSCs) were recorded and we analyzed the effect of
      immunosuppressants on the synaptic potentiation induced by pairing weak
      presynaptic stimulation with postsynaptic depolarization in CA1 neurons of rat
      hippocampal slices. We found that postsynaptic application of rapamycin or FK506,
      at low concentrations, but not cyclosporin A, in conjunction with weak pairing
      stimulation, induced NMDA-dependent long-term potentiation (LTP). The rapamycin
      induced LTP was blocked by chelating intracellular Ca(2+) or by inhibiting the
      intracellular Ca(2+) release. Thus, Ca(2+) release from intracellular Ca(2+)
      stores is required for the induction of LTP by weak pairing stimulation in the
      presence of rapamycin or FK506 at postsynaptic sites. We propose that
      postsynaptic FKBP-12 regulates synaptic transmission by stabilizing the
      postsynaptic Ca(2+) signaling mechanism in rat hippocampal CA1 neurons.

PMID- 10884574
TI  - Transfection efficiency increases by incorporating hydrophobic monomer units into
      polymeric gene carriers.
AB  - The water soluble terpolymer, poly(N-isopropylacrylamide (IPAAm)-co-2
      (dimethylamino)ethyl methacrylate (DMAEMA)-co-butylmethacrylate (BMA)) was
      synthesized, and its efficiency in in vitro gene transfection was evaluated.
      Copolymers with different compositions were synthesized by radical
      polymerization. For a series of copolymers containing 60 mol% of DMAEMA, the
      plasmid bands were retained within the gel loading slot, independent of
      polymer/plasmid weight ratios or BMA monomer content. In contrast, for a series
      of copolymers containing 20 mol% DMAEMA, plasmid bands of complexes were retarded
      with increasing weight ratios. For the copolymer with 10 mol% BMA content, the
      plasmid was completely retained within the gel loading slot. The transfection
      efficiency of polymer/plasmid complexes was evaluated in COS-1 cells using a pCMV
      lacZ plasmid, encoding for beta-galactosidase as a reporter gene. Transfection
      efficiency of a series of copolymers containing 20 mol% of DMAEMA varied with BMA
      content. The transfection efficiency of the copolymers with 0, 2, and 5 mol% of
      BMA was low. The transfection efficiency of the copolymers with 10 mol% of BMA
      was about 2-fold higher than that of the PDMAEMA control homopolymer. The
      transfected cells were observed at a very wide range of polymer/plasmid weight
      ratios. The transfection efficiency of all copolymers containing 60 mol% of
      DMAEMA was lower than that of the PDMAEMA homopolymer.

PMID- 10884575
TI  - Lipid-coated microgels for the triggered release of doxorubicin.
AB  - We have systematically engineered a polymeric, multi-component drug delivery
      system composed of a lipid-coated hydrogel microparticle (microgel). The design
      of this delivery system was motivated by the recent elucidation of the mechanism
      of regulated secretion from the secretory granule and the compositional and
      structural features that underlie its ability to store and release endogenous
      drug-like compounds. The present work describes the assembly and response of a
      prototype construct which displays several important features of the secretory
      granule, including its high drug loading capacity, and triggered microgel
      swelling, resulting in the burst release of drug. To achieve this, ionic
      microgels were synthesized, and loaded with doxorubicin via ion exchange. These
      microgels were then coated with a lipid bilayer, and the release of doxorubicin
      was triggered from the gels using either lipid-solubilizing surfactants or
      electroporation. The use of a microanalytical technique is featured utilizing
      micropipette manipulation that allows the study of the behavior of individual
      microparticles. The lipid-coated microgels were electroporated in saline
      solution; they swelled and disrupted their bilayer coating over a period of
      several seconds and exchanged doxorubicin with the external plasma saline over a
      period of several minutes. It is envisioned that this system will ultimately find
      utility in drug delivery systems that are designed to release chemotherapeutic
      agents and peptides by the application of a triggering signal.

PMID- 10884576
TI  - pH-sensitive freeze-dried chitosan-polyvinyl pyrrolidone hydrogels as controlled
      release system for antibiotic delivery.
AB  - The aim of this study was to develop a pH-sensitive chitosan/polyvinyl
      pyrrolidone (PVP) based controlled drug release system for antibiotic delivery.
      The hydrogels were synthesised by crosslinking chitosan and PVP blend with
      glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN). The
      semi-IPN formation was confirmed by Fourier transform infrared spectroscopic
      (FTIR) analysis. Semi-IPNs, viz, air-dried and freeze-dried, were compared for
      their surface morphology, wettability, swelling properties and pH-dependent
      swelling. Air- and freeze-dried membranes were also incorporated with amoxicillin
      and antibiotic release was studied. Porous freeze-dried hydrogels (pore diameter,
      39.20+/-2.66 microm) exhibited superior pH-dependent swelling properties over non
      porous air-dried hydrogels. A high octane contact angle (144.20+/-0.580) of
      hydrogel was indicative of its hydrophilic nature. Increased swelling of
      hydrogels, under acidic conditions, was due to the protonation of a primary amino
      group on chitosan, as confirmed by FTIR analysis. Freeze-dried membranes released
      around 73% of the amoxicillin (33% by air-dried) in 3 h at pH 1.0 and, thus, had
      superior drug-release properties to air-dried hydrogels. Freeze-dried membranes
      could serve as potent candidates for antibiotic delivery in an acidic
      environment.

PMID- 10884577
TI  - Lysozyme distribution and conformation in a biodegradable polymer matrix as
      determined by FTIR techniques.
AB  - Lysozyme distribution and conformation in poly(lactic-co-glycolic acid)(PLGA)
      microspheres was determined using various infrared spectroscopic techniques.
      Infrared microscopy and confocal laser scanning microscopy indicated that the
      protein was homogeneously distributed inside the microspheres in small cavities
      resulting from the water-in-oil emulsification step. Part of the protein was
      observed at or near the cavity walls, while the rest was located within these
      cavities. Attenuated total reflectance (ATR) and photoacoustic spectroscopy (PAS)
      also showed that there is hardly any protein at the surface of the microspheres.
      Since this microsphere formulation gave a large burst release (ca. 50%), this
      burst release can not be caused by protein at the surface of the particles.
      Probably, the protein is rapidly released through pores in the PLGA matrix.
      Conformational analysis of lysozyme in the PLGA microspheres by KBr pellet
      transmission suffered from band shape distortion and baseline slope. Despite
      incomplete subtraction of the PLGA background, a characteristic band of non
      covalent aggregates at 1625 cm(-1) was observed in the second derivative spectrum
      of the protein Amide I region. The other Fourier-transform infrared (FTIR)
      methods yielded similar results, indicating that the sample preparation procedure
      did not introduce artifacts. The observed aggregation signal may correspond to
      the protein adsorbed to the cavity walls inside the microspheres.

PMID- 10884578
TI  - Influence of process parameters on the protein stability encapsulated in poly-DL
      lactide-poly(ethylene glycol) microspheres.
AB  - Glucose oxidase (GOD) has been encapsulated as a model protein within poly-DL
      lactide-poly(ethylene glycol) (PELA) microspheres to evaluate the activity
      retention during microencapsulation process. This paper was aimed to investigate
      the effect of process parameters, such as the preparation method, the used matrix
      polymer with different compositions, the solvent system and the addition of
      stabilizer on the structural integrity and activity retention of encapsulated
      protein. The stability of the protein released during in vitro assay was also
      assessed. The obtained results showed that the solvent extraction/evaporation
      method based on the formation of double emulsion w(1)/o/w(2) benefited the
      activity retention compared with the phase separation method based on the
      formation of w/o(1)/o(2). And in the emulsion-evaporation system most of the
      protein activity was lost during the first emulsification procedure to form
      primary emulsion w(1)/o (ca. 28%) and the second emulsification procedure to form
      the double emulsion w(1)/o/w(2) (ca. 20%), in contrast to other processes
      occurring during microspheres preparation. The matrix polymer and the solvent
      system in the oil phase had an impressive impact on the activity retention, while
      the addition of gelatin in the internal aqueous phase resulted in no major
      reduction of activity loss. GOD release from PELA microspheres exhibited a
      triphasic profile, that is, the initial burst release during the first day, the
      gradual release over about 1 month, and then the second burst release. The
      encapsulation of GOD in PELA microspheres was effective in reducing its specific
      activity loss. Sixty-seven per cent of the initial specific activity retention
      was detected for the released GOD from microspheres formulation during 1 week of
      incubation, but nearly all the activity was lost for GOD in solution incubated
      under the same condition. SDS-PAGE results showed that, although the activity
      loss was detected, no rough changes of molecular weight of GOD was observed
      during encapsulation procedure and the initial days of incubation into the in
      vitro release medium.

PMID- 10884579
TI  - Kinetics of hydrolysis of dextran-methylprednisolone succinate, a macromolecular
      prodrug of methylprednisolone, in rat blood and liver lysosomes.
AB  - A macromolecular prodrug of methylprednisolone (MP) was synthesized by
      conjugating MP with dextran with a M(W) of 70000 through a succinic acid linker.
      It has been shown previously that the dextran-MP conjugate (DMP) releases MP
      directly or indirectly through formation of methylprednisolone succinate (MPS)
      which is further hydrolyzed to MP. To investigate the suitability of DMP
      conjugate as a prodrug of MP for systemic administration, the kinetics of
      hydrolysis of the conjugate was studied in vitro in rat blood and liver
      lysosomes. In blood, the hydrolysis of MPS to MP was approximately ten-fold
      faster than that in buffer. However, the hydrolysis rate constants of DMP
      conjugate to MP or MPS in blood were not different from those in buffer. Overall,
      the hydrolysis of DMP in the rat blood occurred with a half life of approximately
      25 h. Hydrolysis of MPS to MP also occurred in the liver lysosomal fraction, but
      not in the control samples lacking lysosomes. However, the rate constants for the
      hydrolysis of DMP conjugate to MP and MPS in the lysosomal fraction were not
      significantly different from those in the control samples. These data suggest
      that the slow hydrolysis of DMP conjugate to MP or MPS in both rat blood and
      liver lysosomes occurs mostly, if not completely, via chemical hydrolysis.
      However, the conversion of MPS to MP is apparently enzymatic. The data may have
      significant implications for systemic administration of the prodrug.

PMID- 10884580
TI  - Sustained release of silver from periodontal wafers for treatment of
      periodontitis.
AB  - Periodontal wafers intended to treat the underlying infections in patients with
      periodontitis have been developed. The wafers consist of poly(lactic-co-glycolic
      acid) as a primary bioerodible polymeric component, poly(ethylene glycol) as a
      plasticizer and encapsulation aid, and silver nitrate as the antimicrobial agent.
      The wafers are capable of sustained in vitro release of bioactive silver for at
      least 4 weeks. The wafers exhibit silver release that follows erosion kinetics,
      confirming a bulk erosion/release mechanism. In clinical evaluation, sustained
      release of silver at bactericidal levels for at least 21 days is observed.
      Staining of hard and soft tissues due to the released silver is minimal and
      reversible.

PMID- 10884581
TI  - NMR imaging investigations of drug delivery devices using a flow-through USP
      dissolution apparatus.
AB  - A system for performing NMR imaging experiments on drug delivery devices within a
      flow-through dissolution apparatus, USP Apparatus 4, has been developed. The
      system was used to image the physical changes that occur in solid dosage forms
      during dissolution in the flow-through apparatus. Simultaneous cumulative drug
      release measurements were also made. The NMR images obtained under these
      conditions and the drug release data provide a better understanding of the
      processes involved in the release of drugs from drug delivery systems based on
      diffusion, dissolution and osmosis mechanisms.

PMID- 10884582
TI  - Influence of cholesterol on liposome fluidity by EPR. Relationship with
      percutaneous absorption.
AB  - The influence of liposome composition on bilayer fluidity and its effect on the
      percutaneous absorption into the skin were investigated. Liposomes formed with
      saturated or unsaturated phospholipids (H-PC or PC) with varying amounts of
      cholesterol were prepared and their penetration behaviour into the stratum
      corneum was followed up by means of the stripping method. The order and dynamics
      of the hydrophobic domain of the vesicles were studied using electron
      paramagnetic resonance (EPR) methodology. Phospholipid composition and the amount
      of cholesterol exert a considerable influence on the penetration behaviour of the
      probe encapsulated in the liposomes. This behaviour is closely related to the
      fluidity characteristics of these liposomes studied by EPR. Therefore, a
      penetration mechanism of the vesicles into the skin, based on the incorporation
      of lipids into the skin lipids and on fluidity behaviour, is suggested.

PMID- 10884583
TI  - Drug release from an ensemble of swellable crosslinked polymer particles.
AB  - This paper presents a new model suitable to describe the drug release from drug
      delivery systems constituted by an ensemble of drug loaded crosslinked polymer
      particles. The model accounts for the main factors affecting the drug release
      such as the particle size distribution, the physical state and the concentration
      profile of the drug inside the polymeric particles, the viscoelastic properties
      of the polymer-penetrant system and the dissolution-diffusion properties of the
      loaded drug. In order to check the validity of the model, release experiments
      were performed by using crosslinked polyvinyl-pyrrolidone (PVP) particles and two
      different model drugs, MAP (medroxyprogesterone acetate) and TEM (Temazepam). MAP
      and TEM were chosen because of their completely different dissolution behaviours
      in water. In particular, TEM undergoes a phase transition to the crystalline
      state upon dissolution when it is loaded in the polymeric network in the
      amorphous state. The comparison with the experimental results confirms that the
      most important factors determining the drug release kinetics can be properly
      accounted for.

PMID- 10884584
TI  - Development of oral controlled release preparations, a PVA swelling controlled
      release system (SCRS). II. In vitro and in vivo evaluation.
AB  - A novel controlled release system, the PVA swelling controlled release system,
      was evaluated in vitro and in vivo using emedastine difumarate as a model drug.
      In the in vitro drug release study, the release profile of this system had almost
      zero-order kinetics. The effect of dissolution test conditions, which were paddle
      rotation speed, mechanical stress, and pH of the dissolution medium, on the
      release rate was very small. In an in vivo human bioavailability study of two
      formulations with a different release rate, the absorption rate was dependent on
      the release rate, and both formulations showed constant plasma levels of the drug
      for long periods. The variations of plasma concentration on the simulation of
      repetitive administration of the formulations at 24-h intervals were almost equal
      to the experimental value for the twice daily controlled release capsule
      currently on the market. It is concluded that the PVA swelling controlled release
      system is feasible for a long-acting preparation as a once-daily treatment.

PMID- 10884586
TI  - Edith mathiowitz, donald E. Chickering III, and claus-michael lehr. eds.,
      bioadhesive drug delivery systems. Fundamentals, novel applications and
      development, M. Dekker, new york, NY, xv+670 pages, $195.00

PMID- 10884585
TI  - Formulation of calcium phosphates/poly (d,l-lactide) blends containing gentamicin
      for bone implantation.
AB  - Implants to prevent or treat osteomyelitis are described, composed of
      phosphate/poly(d,l-lactide) blends containing the antibiotic gentamicin. Seven
      formulations of implants containing 3% gentamicin sulfate (GS) were prepared at
      433 MPa and 693 MPa of compression pressure. The blends contained phosphates (25%
      hydroxyapatite (HAP), 75% tricalcium phosphate (TCP)) and 20% dl-PLA (weight
      average molecular weight, M(w): 30 kD). To prolong GS release, implants were
      coated with PLGA (M(w):100 kD) or dl-PLA (M(w): 200 kD). Various durations of GS
      release from these devices were demonstrated as feasible. Release times of more
      than 10 weeks were attained with implants coated with dl-PLA (M(w): 200 kD),
      greatly exceeding the performance of the commercial formulation.

PMID- 10884587
TI  - Synergistic anti-tumor activity of a novel immunomodulator, BCH-1393, in
      combination with cyclophosphamide.
AB  - N,N-dimethylaminopurine pentoxycarbonyl D-arginine (BCH-1393) is a novel low
      molecular weight synthetic immunomodulator that has been shown to significantly
      stimulate cytotoxic T-lymphocyte responses both in vitro and in vivo (Zacharie B,
      Gagnon L, Attardo G, Connolly TP, St-Denis Y, Penney CL. Synthesis and activity
      of 6-substituted purine linker amine immunostimulants. J. Med. Chem. 1997;40:2883
      94). Prompted by this evidence, we extended evaluation of BCH-1393 for anticancer
      activity in syngeneic mouse experimental tumor models. Consistent with previous
      findings, in vitro assessment of BCH-1393 activity demonstrated a significant
      increase in the CTL responses in the range of 10(-9)-10(-5) M. Treatment of mice
      with four consecutive daily intraperitoneal injections at 25 and 50 mg/kg
      resulted in a significant increase of the relative percentage of blood CD4+,
      CD8+, NK and monocyte subsets without any evidence of toxicity. In vivo anti
      tumor activity of BCH-1393 was evaluated, either alone or in combination with
      subtherapeutic doses of cyclophosphamide (Cy), against weakly immunogenic mouse
      breast carcinoma DA-3 and strongly immunogenic colon adenocarcinoma MC38. Daily
      intraperitoneal injection of BCH-1393 at 50 mg/kg alone was well tolerated but
      produced a relatively weak anti-tumor effect in both tumor models. However, a
      significant inhibition of tumor outgrowth and suppression of established tumor
      growth was observed when BCH-1393 was administered in combination with
      subtherapeutic doses of Cy. Combination treatment of 50 mg/kg BCH-1393 with 100
      mg/kg Cy (given as single intravenous bolus injection) starting 2 days prior to
      DA-3 tumor cell inoculation prevented tumor outgrowth in 70-80% of treated mice.
      In the remaining 20-30% of mice that had developed tumors, a nearly complete
      (90%) tumor growth inhibition was observed at days 22-24 post tumor implant. In
      the MC38 tumor model, combination treatment of established tumors with BCH-1393
      and Cy (CTX) at 50 mg/kg resulted in a significant delay in tumor growth compared
      to CTX treatment alone. The observed concomitant anti-tumor activity of BCH-1393
      with cyclophosphamide warrants further investigation of this immunomodulator as
      an adjunctive treatment of cancer.

PMID- 10884588
TI  - Hydroxyzine inhibits experimental allergic encephalomyelitis (EAE) and associated
      brain mast cell activation.
AB  - Experimental allergic encephalomyelitis (EAE) has been used as an animal model
      for the human demyelinating disease multiple sclerosis (MS). In acute MS or EAE,
      early disruption in the integrity of the blood-brain-barrier (BBB) precedes brain
      infiltration by inflammatory cells or any clinical evidence of disease. BBB
      permeability could be affected by vasoactive mediators and cytokines released
      from perivascular brain mast cells. We investigated the number and degree of
      activation of brain mast cells in EAE and the effect of the heterocyclic
      histamine-1 receptor antagonist hydroxyzine, a piperazine compound known to also
      block mast cells. Acute EAE was induced in Lewis rats by immunization with whole
      guinea pig spinal cord homogenate and complete Freund's adjuvant (CFA). A second
      group of animals were treated orally with hydroxyzine for one day before
      immunization and then continuously for 14 days. Control rats were treated with
      CFA or hydroxyzine alone. The clinical progression of EAE was assessed on days
      10, 12 and 14 after immunization. The number of metachromatic mast cells and the
      degree of degranulation was assessed in the thalamus with light microscopy. At
      day 14, there was a three-fold increase in the number of brain mast cells with
      EAE, as compared to controls. These cells were positive for the immunoglobulin E
      binding protein (FcepsilonRI), while those from control rats were not. Over 40%
      of all thalamic mast cells studied in EAE showed partial staining or extruded
      secretory granule indicative of secretion. Hydroxyzine treatment inhibited
      (p<0.05) the progression and severity of EAE by 50% and the extent of mast cell
      degranulation by 70% (p<0.05). These findings indicate that brain mast cells are
      associated with EAE development and that inhibition of their activation
      correlates positively with the clinical outcome.

PMID- 10884589
TI  - Inhibitory effect of sodium salicylate on nitric oxide production from TM4
      sertoli cells.
AB  - Nitric oxide (NO) has been proposed to play a role in a variety of inflammatory
      diseases. Sodium salicylate (NaSal) is the most commonly used anti-inflammatory
      agent. We investigated whether NaSal can diminish the production of NO in TM4
      Sertoli cells. TM4 Sertoli cells produced a small amount of NO upon treatment
      with recombinant interferon-gamma (rIFN-gamma). The effect of rIFN-gamma was
      enhanced markedly by the addition of recombinant TNF-alpha (rTNF-alpha) in a dose
      dependent manner. NaSal (10 and 20 mM) significantly inhibited NO production from
      TM4 Sertoli cells induced by rIFN-gamma plus rTNF-alpha. In addition, rIFN-gamma
      in combination with rTNF-alpha showed a marked increase of the expression of
      inducible NO synthase (iNOS) protein. Western blot analysis revealed that NaSal
      (10 and 20 mM) blocked a step of iNOS protein synthesis. The rIFN-gamma plus rTNF
      alpha-induced nuclear factor-kappaB (NF-kappaB) activation was significantly
      blocked by NaSal (10 and 20 mM). On the other hand, neither staurosporine nor
      polymyxin B significantly inhibited NO production from TM4 Sertoli cells induced
      by rIFN-gamma plus rTNF-alpha. The present results indicate that NaSal inhibits
      rIFN-gamma plus rTNF-alpha-induced NO production in TM4 Sertoli cells via the
      signal transduction pathway of NF-kappaB activation.

PMID- 10884590
TI  - Effect of all-trans-retinoic acid on cytokine production in a murine macrophage
      cell line.
AB  - All-trans-retinoic acid (RA) is a cancer chemopreventive agent and a pluripotent
      morphogen. It belongs to the class of retinoids that, besides being inducers of
      differentiation and growth-inhibitos, exert immunomodulatory and anti
      inflammatory functions by mechanisms that are not clearly understood. Macrophages
      play different roles in diverse physiological processes, including ones in
      orchestrating immune and inflammatory responses. Products of activated
      macrophages such as interleukin-1beta (IL-1beta), tumor necrosis factor alpha
      (TNFalpha), interleukin-6, interleukin-8, and nitric oxide (NO) are important
      regulators of inflammatory reactions. In this study J774A. 1 cells, a murine
      macrophage cell line, was used to study the effects of RA on the production of
      NO, TNFalpha and IL-1beta. Cells were stimulated with lipopolysaccharide (LPS)
      with or without RA. RA depressed the levels of NO in a dose-dependent manner. NO
      production and subsequent nitrite accumulation in the media peaked at 24 h,
      plateaued at 48 h, and remained at the same level through 72 h. The presence of
      RA decreased TNFalpha levels, measured by both bioassay and enzyme-linked
      immunosorbent assay (ELISA), but these did not correlate with increased mRNA
      expression measured by reverse-transcriptase polymerase chain reaction at 6 h
      after LPS stimulation. IL-1beta protein production measured by both ELISA and
      bioassay decreased with RA treatment. IL-1beta mRNA expression was not affected
      by RA except at low doses. This study indicated that RA modulates cytokine
      production in J774A.1 macrophage cells. Inhibition of inflammatory cytokine
      production may play a role in the anti-inflammatory activity of RA. The results
      suggested that effects of RA are complex and are time and concentration
      dependent.

PMID- 10884591
TI  - In vivo acute depletion of CD8(+) T cells before murine cytomegalovirus infection
      upregulated innate antiviral activity of natural killer cells.
AB  - In this study, we investigated the effect of depletion of CD8(+) T cells on the
      activity of natural killer (NK) cells at an early phase of murine cytomegalovirus
      (MCMV) infection. For CD8(+) T cell depletion, mice were intraperitoneally
      treated with anti-CD8 mAb, purified from 2.43 hybridoma, for 2 consecutive days
      before or after infection. Three days after infection, we found that an acute
      depletion of CD8(+) T cells before infection caused a significant decrease in the
      viral load in liver and spleen. This effect coincided with an increase in numbers
      of CD3(-) NK1.1(+) cells in spleen and their expression of the early activation
      molecule CD69. Although cytolytic activity of NK cells increased on day 3 of
      infection in CD8-depleted mice, the level of IFN-gamma decreased in serum and
      supernatant of cultured spleen cells. In contrast to the effect of acute
      depletion of CD8(+) T cells before infection, the depletion after infection had
      no effect on the viral load or number and cytolytic function of NK cells. Lack of
      effects of CD8(+) T cell depletion on the viral load and NK cytolytic activity is
      also observed in CD8(+) knockout mice. In conclusion, the results suggest that an
      acute depletion of CD8(+) T cells before MCMV infection effectively upregulated
      the antiviral activity of NK cells. This effect appears to be mediated through an
      increase in numbers, activation and cytolytic activity of NK cells.

PMID- 10884592
TI  - Interleukin 1beta and GABA-transaminase activity in rat thymus.
AB  - The occurrence and distribution of 4-aminobutyrate:2 oxoglutarate transaminase
      (GABA-t) activity were examined in the rat thymus of normal and immunostimulated
      rats using biochemical and histoenzymatical methods. Specific GABA-t reactivity
      was confined primarily to the arteries and, to a lesser extent, to the veins.
      Only a few activities could be observed in association with the subcapsular and
      medullar part of the parenchyma and nerve fibers. GABA-t was considered a linking
      enzyme between the immune and the nervous system and it was studied with the aim
      of analyzing the relationships between these two systems. Our findings indicate
      that the GABA-t activity in the thymus is specifically located in the wall of the
      blood vessels. Moreover, our results demonstrate the presence of a GABA-t
      activity in the peripheral blood vessels. Treatment with interleukin 1beta
      induces an increase of protein content of the amounts of GABA-t biochemically
      assayed and of the levels of histoenzymatically stained GABA-t. Furthermore,
      staining of the different structures of the thymus in treated or untreated rats
      shows that the significant modifications concern the parenchyma, the structures
      resembling nerve fibers and finally, the whole thymus. On the contrary, the
      highest activity of the GABA-t is located in the walls of arteries, veins and
      lymphatic vessels.

PMID- 10884593
TI  - Protective effect of black seed oil from Nigella sativa against murine
      cytomegalovirus infection.
AB  - In this study, antiviral effect of black seed oil (BSO) from Nigella sativa was
      investigated using murine cytomegalovirus (MCMV) as a model. The viral load and
      innate immunity mediated by NK cells and M&phi; during early stage of the
      infection were analyzed. Intraperitoneal (i.p.) administration of BSO to BALB/c
      mice, a susceptible strain of MCMV infection, strikingly inhibited the virus
      titers in spleen and liver on day 3 of infection with 1x10(5) PFU MCMV. This
      effect coincided with an increase in serum level of IFN-gamma. Although BSO
      treatment decreased both number and cytolytic function of NK cells on day 3 of
      infection, it increased numbers of M&phi; and CD4(+) T cells. On day 10 of
      infection, the virus titer was undetectable in spleen and liver of BSO-treated
      mice, while it was detectable in control mice. Although spleen of both control
      and BSO-treated mice showed similar CTL activities on day 10 after infection,
      serum level of IFN-gamma in BSO-treated mice was higher. Furthermore, BSO
      treatment upregulated suppressor function of M&phi; in spleen. These results show
      that BSO exhibited a striking antiviral effect against MCMV infection which may
      be mediated by increasing of M&phi; number and function, and IFN-gamma
      production.

PMID- 10884594
TI  - Altered electrophysiological characteristics of developing rat cortical neurones
      after chronic methylmercury chloride treatment.
AB  - The effect of methylmercury chloride on the excitability of developing cortical
      neurons was tested. Methylmercury was administered in the drinking water to
      pregnant rats during gestation and suckling period and the offspring were
      investigated. The electrical characteristics of the neuronal membranes as well as
      the synaptic responses evoked by electrical stimulation of the corpus callosum
      were measured in brain slices. Slices prepared from the somatosensory cortex of 4
      week-old rats were analyzed using sharp electrode intracellular
      microelectrophysiological recording technique. Long-lasting treatment with low
      doses of methylmercury chloride caused a slight decrease in the membrane
      potential and in the amplitude of spikes together with an enhanced excitability.
      Some of the treated animals were grown up without any further methylmercury
      application, and their offspring (second generation) were also studied
      electrophysiologically. These untreated offspring had normal neuronal
      characteristics. The altered membrane characteristics detected in the 4-week-old
      MeHg treated animals might be the consequence of the abnormal developmental
      processes taking place in the presence of MeHg which may alter the normal
      neuronal excitability. Besides this, the acute toxic effect of Hg(2+), which was
      present in the brain at the time of investigations, has to be taken into
      consideration.

PMID- 10884595
TI  - Expression of calbindin-D28k and parvalbumin during development of rat's
      basolateral amygdaloid complex.
AB  - Parvalbumin and calbindin-D28k are calcium-binding proteins, which are considered
      to be markers for certain populations of GABAergic neurons. Their correct
      development in the basolateral amygdaloid complex is critical for the proper
      emotional functioning in adult live of human and animals. Therefore, in this
      paper we describe the pattern of the morphological differentiation and
      distribution of immunoreactive elements of the parvalbumin and calbindin-D28k in
      this complex on the basis of immunohistochemically stained material obtained from
      embryonic (E20) and postnatal (P0-P90) rat brains. Calbindin-D28k appeared early
      in the development, already in the prenatal life. At this time immunopositive
      reaction was visible only in cell bodies. However, during development the
      population of immunopositive neurons was divided into four types: (1) polygonal;
      (2) piriform-like; (3) bipolar; and (4) pyramidal-like. Two weeks after birth
      calbindin-D28k immunoreactivity also appeared in neuropil. First, there were
      visible calbindin-D28k positive fibers and granules that encircled unstained cell
      bodies and formed basket-like structures. Subsequently, these granules appeared
      along proximal parts of unstained dendrites forming, so called 'cartridges'. The
      distribution of calbindin-D28k positive cells during postnatal life was rather
      homogenous throughout whole basolateral complex. Intensity of calbindin-D28k
      immunoreactivity reached mature level on the 21st day after birth.The maturation
      pattern of parvalbumin immunopositive elements followed the same sequence as
      calbindin-D28k, but it started much later - since the 17th day after birth and
      reached mature appearance on the 30th day of life. Contrary to calbindin-D28k,
      parvalbumin was not homogeneously distributed in the basolateral complex.
      Originally, parvalbumin was restricted to the magnocellular part of basolateral
      nucleus but it was finally expressed also in the parvicellular part of
      basolateral nucleus and the dorsolateral part of lateral nucleus. The differences
      in development of these two calcium-binding proteins indicate that parvalbumin
      and calbindin-D28k play diverse roles during development and maturation of the
      basolateral amygdala.

PMID- 10884596
TI  - Age-related changes in the localization of P2X (nucleotide) receptors in the rat
      adrenal gland.
AB  - Observation of the changes in the occurrence and distribution of nucleotide (P2X)
      receptors in the adrenal gland during development and ageing, and correlation
      with the changes in adrenal status at similar stages may give morphological
      insights into the functions of purine nucleotides in the gland. Age-related
      changes in the localization of all seven subtypes of the P2X receptor in the
      adrenal gland of rat were therefore investigated immunohistochemically. In the
      adrenal glands of prenatal rats, immunoreactivity to P2X receptor subtypes was
      not observed. In glands of the postnatal rat at the developmental stages studied,
      only immunoreactivity for the P2X(5) receptor subtype was observed. A small
      number of faintly P2X(5)-immunoreactive chromaffin cells were found in the
      adrenal glands of 1-day-old rats; the frequency of localization and intensity of
      staining of immunoreactive cells had increased by day 4 and was further increased
      at day 7. P2X(5) immunoreactivity was not observed in the adrenal glands from 14-
      and 21-day-old rats. At 8 weeks of age, immunoreactivity with a specific
      distribution for each of the seven receptor subtypes was observed. Except for the
      P2X(4) receptor, adrenal glands at 24 months showed a similar pattern of
      immunoreactivity for the receptor subtypes as that observed at 8 weeks.
      Immunoreactivity for P2X(4) was first observed in the adrenal cortical cells of
      the zona reticularis at 8 weeks, but was absent in 24-month-old rats. However,
      several P2X(4)-immunoreactive chromaffin cells appeared at 24 months. Such
      immunoreactive cells were not seen in rats of any of the other ages studied. It
      was concluded that the greater expression of P2X(5) receptor at an early
      developmental stage and of P2X(4) in ageing might reflect functional roles for
      purines in cellular proliferation and/or differentiation, and in cellular
      degeneration, respectively, in adrenal glands of rat.

PMID- 10884597
TI  - Methamphetamine-induced striatal dopamine release, behavior changes and
      neurotoxicity in BALB/c mice.
AB  - The behaviors associated with the neurotoxic effects of methamphetamine were
      evaluated in BALB/c mice. Hyperthermia and behavioral observations were measured
      60 min after each subcutaneous injection of methamphetamine (4x4 or 8 mg/kg) or
      saline, each given 2 h apart. The behavioral observations included stereotyped
      behaviors, incidence of hemorrhage in breast, salivation and self-injurious
      behavior (SIB). Repeated administration of methamphetamine produced these
      behavioral changes and hyperthermia, but resulted in hypothermia by the final
      injection (8 mg/kg). In addition, the methamphetamine treatment induced a long
      lasting dopamine depletion of similar magnitude in the 4 and 8 mg/kg-treated
      animals. In a time course study striatal monoamine levels were measured 60 min
      after each injection of these doses. The first and second injections of
      methamphetamine (8 mg/kg) produced a drastic increase in striatal 3
      methoxytyramine; this failed to occur after the third or fourth injection of the
      same dose. In contrast, 4 mg/kg of methamphetamine also produced an increase in 3
      methoxytyramine after the second and third injections of the drug and, in this
      case, these were maintained for the duration of the treatment. Striatal 3, 4
      dihydroxyphenylacetic acid levels also drastically decreased following both doses
      of methamphetamine, suggesting inhibition of monoamine oxidase in striatum.
      Moreover, a single injection of methamphetamine increased striatal 2,3
      dihydroxybenzoic acid formation. These results suggest that the incidence of
      hyperthermia, SIB and striatal dopamine neurotoxicity are closely linked to
      striatal dopamine release and inhibition of monoamine oxidase produced by
      methamphetamine in BALB/c mice.

PMID- 10884598
TI  - Heterochronous maturation of regional brain astroglia: neuronal modulation of
      striatal glial cells differentiation ex vivo.
AB  - Subcultured astroglial cells from striatum, cerebral cortex and ventral
      mesencephalon obtained from primary cultures of fetal (E14, E17 and E21) or
      postnatal (days 5-6) rats showed different regional, age-dependent morphological
      response (stellation) to cyclic AMP. While most of the cerebral cortex and
      ventral mesencephalic astroglial cell population was responsive at all ages
      tested, striatal cells at E14 and E17 were not. At age E21 striatal astroglia
      showed a significant shift toward a mature-like type of response to cyclic AMP.
      Postnatal striatal astroglia responded to cyclic AMP as the cortical and ventral
      mesencephalic astroglia did, with generalized stellation. Prenatal striatal
      astroglia was characterized immunocytochemically as A2B5+, fibronectin+,
      vimentin+, S-100+ and GFAP-. Failure of early prenatal (E14, E17) striatal
      astroglia to differentiate in response to cyclic AMP, was overcome by previous (5
      7 days) co-culture with primary cell dissociates from postnatal-, but not from
      prenatal donors, from all brain regions tested including a non-target region for
      striatal cells, such as septum. This effect was duplicated when striatal
      astroglia was co-cultured with cell populations enriched in neurons through
      Percoll gradients. Only cell-to-cell contact co-cultures were able to induce a
      change in the studied response. Dead neuron-enriched populations obtained
      following various types of physical treatments were also able to change
      significantly striatal cell response toward cyclic AMP. Enriched astroglial
      populations from postnatal donors did not change striatal astroglial response
      toward cyclic AMP, except for ventral mesencephalic astroglia which induced a
      comparatively reduced but significant increase in striatal cell responsiveness.
      It is concluded that astroglial maturation and potential for phenotype expression
      during brain development proceeds with regional heterochrony. Also, that
      maturation of prenatal striatal astroglia responsiveness toward cyclic AMP is
      inducible by non-diffusible factors, probably of neuronal origin, expressed in
      live or dead primary cultures from various, homotopic and heterotopic, postnatal
      brain regions. It is further suggested that striatal afferents and/or mature
      local striatal neurons express membrane associated molecules that regulate
      responsiveness for phenotype expression of striatal glial cells, thus reinforcing
      the concept of a highly interactive, continuous neuron-glial developmental
      process that takes place during brain organization.

PMID- 10884599
TI  - ET-18-OCH(3)-induced cytotoxicity and DNA damage in rat astrocytes.
AB  - The ether lipid 1-octadecyl-2-methyl-rac-glicero-3-phosphocholine (ET-18-OCH(3))
      is known to be selectively cytotoxic toward several types of tumor cells, in
      which it seems to activate a process of apoptotic cell death. Moreover, the drug
      has been demonstrated to be active in normal cells too, particularly in rat
      astrocytes. In these cells at low dosage (from 1 to 6 microg/ml of medium) ET-18
      OCH(3) stimulates maturation and protective responses, whereas at increasing
      dosages (from 8 to 20 microg/ml) it shows cytotoxic effects. The present study
      demonstrates that when ET-18-OCH(3) is added to astrocytes, it activates, in a
      time- and concentration-dependent manner, an oxidative process by increasing both
      the generation of reactive oxygen species (ROS), including nitric oxide, and
      lipid peroxidation. When there is a high ET-18-OCH(3) concentration or the time
      of treatment is prolonged, the increased oxidative condition seems to trigger DNA
      fragmentation (monitored by COMET assay) as well as loss in cell viability. These
      cytotoxic effects indicate that ROS may be considered, in our experimental model,
      as executioners of a program of cell death. In addition, ET-18-OCH(3) being a
      promising molecule in antitumor therapy, our data, while reinforcing the
      importance of monitoring the therapeutic drug dosage employed, also suggest that
      it may be useful to associate some antioxidants with antitumor treatments.

PMID- 10884600
TI  - Synaptophysin immunoreactivity in spinal white matter of young adult rats.
AB  - Patterns of synaptophysin immunoreactivity were examined in the ventral and
      lateral funiculi of rat lumbosacral spinal cords. In normal young adults,
      dendrites from neurons in the spinal gray matter extended into the ventral and
      lateral white matter as finger-like projections, immunopositive for
      synaptophysin. These projections appeared to diminish in size as they extended
      peripherally and, in general, did not reach the surface of the spinal cord, so
      that the outer one-third to one-fourth of the funiculi contained little or no
      immunoreactivity. The spinal cords of some of the animals studied were X
      irradiated on the third postnatal day. When examined 6 weeks to 5 months later,
      the pattern of synaptophysin immunoreactivity was found to be markedly altered in
      these animals. In general, the synaptophysin immunoreactivity in the white matter
      was less organized than in the non-irradiated rat. As a result, the finger-like
      projections, particularly into the lateral funiculi, were not as distinct, and
      the immunoreactivity appeared to be more diffusely distributed in the white
      matter. Further, the immunoreactivity was present throughout the thickness of the
      white matter in the irradiated animals and subpial concentrations were evident,
      especially along the lateral aspect of the spinal cord. Ultrastructural
      evaluation of the synaptic profiles revealed no differences between irradiated
      and non-irradiated animals. The synapses occurred on both the shafts of the
      dendrites and on the spines. In general, both dendrites and axon terminals were
      covered by astrocyte processes except at synaptic sites, and the synaptic
      complexes were surrounded by astrocyte processes. Although the mechanisms
      underlying the altered pattern of synaptophysin immunoreactivity are not yet
      understood, they may be related to radiation-induced effects on the glial
      populations previously reported by the investigators and/or to radiation-induced
      alterations in reorganization or maturation of dendritic trees.

PMID- 10884601
TI  - Neonatal 6-hydroxydopamine treatment affects GABA(A) receptor subunit expression
      during postnatal development of the rat cerebellum.
AB  - Neurotoxic elimination of noradrenergic terminals by 6-hydroxydopamine (6-OHDA)
      leads to alteration of the granule cell layer formation. We have studied the
      developmental expression of GABA(A) receptor subunits in rat cerebellum after
      neonatal administration of 6-OHDA during the first postnatal month of life. 6
      OHDA was injected subcutaneously. The expression of GABA(A) receptor subunits was
      studied by in situ hybridization and immunohistochemistry. The alterations were
      observed in the neocerebellum - the part of the cerebellum which starts
      development postnatally. The migration of granule cells was delayed, and the
      total area of the granule cell layer in the neocerebellum from 6-OHDA-treated
      rats was reduced to 22.6+/-5% of the corresponding area from control rats. In
      situ hybridization with subunit-specific antisense oligonucleotide probes was
      performed for alpha1, alpha2, alpha3, alpha5, alpha6, beta1, beta2, gamma1 and
      gamma2 subunits of the GABA(A) receptor. In neocerebellum, 6-OHDA treatment
      caused a significant reduction in the alpha1, alpha6 and gamma2 subunit mRNA
      levels. The expression of the other subunits was not changed. It has been shown
      that in the postnatal cerebellum alpha1 and alpha6 subunits can be detected in
      granule cells only when the cells had migrated to their final destination. Our
      findings indicate that a noradrenergic influence may be necessary for the normal
      maturation and migration of cerebellar granule cells.

PMID- 10884602
TI  - Analysis of cerebrocortical neuronal migration in three-dimensional fetal mouse
      cerebral explants: comparison with in vivo.
AB  - Organotypic cultures of cerebral mantle offer a useful method for in vitro
      investigation of mechanisms involved in the migration of neuronal precursors to
      the neocortex. Studies reported to-date have indicated that, while neurons
      continue to migrate in cerebral explant cultures for a few days, they eventually
      stop migrating and fail to reach their pre-programmed destinations and thus
      distinct layers fail to develop within the cortical plate. Hypothesizing that
      this migrational arrest stemmed, in part, from severe distortion and flattening
      of explants in the roller-tube culture method used in previous studies by others,
      we studied neocortical neuronal migration using a recently developed three
      dimensional explant culture system. Explants 300-350 microm thick were derived
      from E16 fetal mouse cerebrum 24 h following administration of 5
      bromodeoxyuridine (BrdU), encased in collagen, placed on porous membranes, and
      alternately exposed to medium and air on a rocking platform. Cultures were
      maintained for 7, 11 and 14 days, then analyzed for the location of BrdU-labeled
      cells. Newborn mice labeled at E15 and analyzed at P1 and P9 served as controls.
      In the explants, labeled cells continued to migrate into the cortical plate until
      11 days in culture, at which point the ventricular zone had disappeared and two
      distinct cortical cell layers sometimes developed. BrdU-labeled cells were
      present throughout the cortical plate, particularly the mid portion. In P9
      controls, five distinct cortical layers were present with labeled cells mostly in
      the outer half (layers II, III). Thus, preservation of three-dimensional tissue
      integrity in culture was accompanied by a modest improvement in migration of
      neurons to the neocortex in comparison with previous reports. The fact that
      normal layer formation failed to develop in thick explants suggests that factors
      other than tissue distortion contribute to this outcome.

PMID- 10884603
TI  - Developmental expression of phospholipase D2 mRNA in rat brain.
AB  - Phospholipase D (PLD) is a ubiquitous enzyme involved in many important cellular
      functions. Rat brain PLD isoforms have recently been cloned and characterized,
      but the expression of this gene has not been well studied. We thus examined the
      developmental expression of PLD2 in postnatal brains by Northern blotting
      employing a non-radioactive RNA probe. Two PLD2 mRNA transcripts of 3.9 and 10.8
      kb were detected in different brain regions and various tissues of the rat. In
      postnatal brains, the level of PLD2 mRNA transcripts are low 1 day after birth,
      increase progressively during development, and reach the maximum level in the
      adult brain. We thus conclude that rat brain PLD2 mRNA is developmentally
      regulated.

PMID- 10884604
TI  - Long-term microglial and astroglial activation in the hippocampus of trimethyltin
      intoxicated rat: stimulation of NGF and TrkA immunoreactivities in astroglia but
      not in microglia.
AB  - In the present study we investigated the microglial and astroglial response after
      trimethyltin (TMT) exposure over a prolonged period of time. Male Wistar rats
      were given a single dose of TMT (8 mg/kg, i.p.) and survived 4, 7, 21, 60 and 180
      days after the administration of the toxin. Histochemistry (Griffonia
      simplicifolia lectin staining) and immunocytochemistry for GFAP were applied to
      identify micro- and astroglial cells, respectively. To assess the trophic
      response of glial cells (NGF and TrkA expression), single or double staining
      experiments were performed. In addition, the biochemical evaluation of GFAP and
      NGF were carried out at chosen timepoints using immunoblotting technique and
      ELISA, respectively. The main findings of our study were as follows. (1) A
      protracted activation of microglia (at least up to 2 months posttreatment). (2) A
      long-lasting expression of GFAP immunoreactivity (at least up to 6 months
      posttreatment) and a steady increase in GFAP content (at least up to 2 months
      posttreatment). (3) The appearance of enormously enlarged, round-shape astrocytes
      exclusively localized to CA1 and observed 2 months posttreatment. (4) The
      stimulation of NGF and TrkA expression in reactive astrocytes. (5) The strongest
      activation of micro- and astroglia coincided with the most prominent
      neurodegeneration in the hippocampus, i.e., in CA4/CA3c and CA1. It is tempting
      to assume that the activation of glial cells in the hippocampal areas
      particularly vulnerable to TMT may affect neuronal fate after neurotoxic insult.

PMID- 10884605
TI  - Modulation of glutamate neurotoxicity on mesencephalic dopaminergic neurons in
      primary cultures by the presence of striatal target cells.
AB  - Glutamate toxicity was compared in substantia nigra (SN)/striatum (STR) and
      SN/cerebellum (CRB) co-cultures on both the entire neuronal population (neuron
      specific enolase (NSE) immunopositive cells) and dopaminergic neurons (tyrosine
      hydroxylase (TH) immunopositive cells). In SN/CRB co-cultures NSE- and TH
      positive cells were more sensitive to glutamate-induced toxicity than in SN/STR
      co-cultures. Moreover, in SN/STR co-cultures as compared to SN/CRB and SN
      cultures, glutamate toxicity was prevented to a larger extent by TCP, a non
      competitive NMDA antagonist. These results suggest that target cells induce a
      differential expression of the different glutamate receptor subtypes in
      mesencephalic dopaminergic cells. Alternatively, the presence of target cells may
      induce the selective development of a subpopulation of dopaminergic neurons
      expressing predominantly NMDA receptors.

PMID- 10884606
TI  - Genotype to phenotype: challenges and opportunities.

PMID- 10884607
TI  - Mycobacterium genavense infection in normal and immunodeficient mice.
AB  - Mycobacterium genavense is a recently described microorganism causing
      disseminated infections in AIDS patients. In this study, we investigate its
      pathogenicity in mice and some mechanisms of the host response to this bacterium.
      Following an intravenous challenge of 10(6) organisms, M. genavense grew
      progressively in the spleens and livers of BALB/c and CBA mice over at least an 8
      month period. Granulomas were present in the spleens, livers and lungs of the
      animals. The numbers of bacteria recovered from the spleens and livers were
      higher in BALB/c (Bcg(s)) than in CBA (Bcg(r)) mice from day 30. The role of the
      Bcg gene, in the early phase of infection, was supported by the fact that the
      bacterial load, on day 15, was higher in BALB/c than in the congenic C.D2
      (Bcg(r)) mice. The role of T cells in the host response was suggested by the high
      susceptibility of nude mice to M. genavense infection. In vivo depletion
      experiments in CBA mice indicated that gamma interferon and both CD4(+) and
      CD8(+) T cells participate in the containment of the bacterial load.

PMID- 10884608
TI  - Genetic differences in the Chlamydia trachomatis tryptophan synthase alpha
      subunit can explain variations in serovar pathogenesis.
AB  - The human pathogen Chlamydia trachomatis is an obligate intracellular bacterium,
      characterized by a developmental cycle that alternates between the infectious,
      extracellular elementary bodies and intracellular, metabolically active
      reticulate bodies. The cellular immune effector interferon gamma (IFN-gamma)
      inhibits chlamydial multiplication in human epithelial cells by induction of the
      tryptophan degrading enzyme indoleamine 2,3 dioxygenase. IFN-gamma causes
      persistent C. trachomatis serovar A infections with atypical reticulate bodies
      that are unable to redifferentiate into elementary bodies and show diminished
      expression of important immunogens, but not of GroEL. However, the sensitivity to
      IFN-gamma varies among serovars of C. trachomatis. In our previous study
      significant IFN-gamma-specific, but tryptophan reversible, induction of proteins
      in C. trachomatis A and L2 with molecular masses of approximately 30 and 40 kDa
      was observed on 2D-gels. The 30-kDa protein from C. trachomatis L2 migrated with
      a significantly lower molecular weight in C. trachomatis A. In this paper we
      include C. trachomatis B, C and D in our investigations and identify the proteins
      as alpha- and beta-subunits of the chlamydial tryptophan synthase using matrix
      assisted laser desorption/ionization mass spectrometry. DNA sequencing of the
      trpA genes from C. trachomatis A and C shows that the TrpA in these serovars is a
      7.7-kDa truncated version of C. trachomatis D and L2 TrpA. The truncation
      probably impairs the TrpA activity, thus elucidating a possible molecular
      mechanism behind variations in the pathogenesis of C. trachomatis serovars.

PMID- 10884609
TI  - Helicobacter pylori infection in wild-type and cytokine-deficient C57BL/6 and
      BALB/c mouse mutants.
AB  - Helicobacter pylori causes gastroduodenal ulcer disease in humans. T lymphocytes
      and their cytokines are thought to play a substantial role in the control of H.
      pylori infection. To determine the importance of T helper (Th) cytokines and
      background genes we investigated the natural course of H. pylori infection in
      BALB/c and C57BL/6 wild-type or mutant mice deficient for either interleukin (IL)
      4 or interferon (IFN)-gamma. H. pylori SPM 326 persisted for at least six months
      in C57BL/6 but was cleared by BALB/c wild-type mice nine weeks postinfection. H.
      pylori was recovered more frequently from IFN-gamma(-/-) BALB/c and IFN-gamma( -/
      ) C57BL/6 mice than from the respective wild-type animals. In contrast, IL-4
      deficiency had no detectable effect on H. pylori recovery rates from either
      strain of mice. Our data suggest a protective role of IFN-gamma by mediating
      inflammation in murine H. pylori infection. In addition, our data emphasize that
      background genes which differ between BALB/c and C57BL/6 mice regulate the
      clearance of H. pylori.

PMID- 10884610
TI  - Characterization of apoptosis induced by sorbitol: a unique system for the
      detection of antiapoptotic activities of viruses.
AB  - The treatment of HEp-2 cells with sorbitol induced massive apoptosis rapidly.
      This method for inducing apoptosis is very useful to detect antiapoptotic
      activity of viruses as well as viral genes. Commitment to death occurred
      immediately upon incubation with sorbitol, even in the presence of pancaspase
      inhibitor, Z-VAD-FMK. Apoptosis is also induced by other polyhydric alcohols with
      more than four hydroxyl groups, but not induced by glycerol or ethylene glycol.
      Sorbitol treatment on ice did not induce apoptosis either. These results suggest
      that this induction of apoptosis does not result simply from high osmotic
      pressure but probably by the interaction of solutes through their physical nature
      (such as hydrophobicity) with the plasma membrane of the cells.

PMID- 10884611
TI  - Genotyping of Tunisian hepatitis B virus isolates based on the sequencing of
      preS2 and S regions.
AB  - The S nucleotide sequences of five hepatitis B virus strains isolated from plasma
      samples of Tunisian patients with chronic hepatitis B were determined; the preS2
      region of three of them were sequenced. According to the comparative analysis of
      S peptide sequences with the reported sequences in the database bank, the five
      hepatitis B strains were shown to be related to the D genotypic group, subtype
      ayw. The nature of residues at positions 125 and 127 allowed us to distinguish
      between each subtype of the D group and to class all five Tunisian sequences in
      the 'ayw2' subtype. Moreover, two of them (1366 and 523) contained a substitution
      of the invariant Cys69 by Arg and Cys221 by Phe, respectively. Potential
      structural modifications due to the Cys-Arg change are discussed.

PMID- 10884612
TI  - Peripheral pathogenesis of prion diseases.
AB  - Prions are infectious pathogens that cause a group of neurodegenerative diseases
      characterized by spongiform degeneration of the central nervous system. Prions
      appear to lack any informational nucleic acid. The most notable prion diseases
      include bovine spongiform encephalopathy, scrapie in sheep and Creutzfeldt-Jakob
      disease of humans. Transmission is thought to be achieved through conversion of a
      normal host protein into a pathological isoform. Although the main pathological
      changes during the course of the disease occur in the brain, the infectious agent
      accumulates early in lymphoid tissue. The subsequent development of clinical
      disease depends on the presence of an intact immune system including mature B
      cells. In this article we review the state of knowledge on the routes of
      neuroinvasion used by the infectious agent in order to gain access to the central
      nervous system upon entry into extracerebral sites.

PMID- 10884613
TI  - CD1-mediated antigen presentation of glycosphingolipids.
AB  - CD1 proteins are distinguished by their ability to present lipid antigens to T
      cells. Group II CD1 or CD1d molecules are recognized by the specialized NK T-cell
      subset, and this reactivity can be greatly augmented by alpha-galactosylceramide,
      a glycosphingolipid derived from a marine sponge. Human CD1b, which is only
      distantly related to the CD1d molecules, can present mammalian glycosphingolipids
      (gangliosides) to autoreactive T-cell clones derived from multiple sclerosis
      patients. Thus, CD1 responsive and glycosphingolipid-reactive cells may play an
      important immune regulatory role, in addition to their well-characterized role in
      the response to microbial lipids.

PMID- 10884614
TI  - The journey of the malaria sporozoite through its hosts: two parasite proteins
      lead the way.
AB  - Malaria is transmitted to a mammalian host when the sporozoite stage of the
      Plasmodium parasite is injected by a mosquito vector. Sporozoites are unique in
      being able to interact with both hosts. Formed and released in the mosquito
      midgut, sporozoites bind to the salivary glands and invade their secretory cells.
      Once injected into the mammalian host, they home to the liver and invade
      hepatocytes. Recent work has shown that two sporozoite surface proteins, CS and
      TRAP, act in both hosts, perform multiple functions, and are each essential for
      the parasite at more than one step of its life cycle.

PMID- 10884615
TI  - Cell polarization and adhesion in a motile pathogenic protozoan: role and fate of
      the Entamoeba histolytica Gal/GalNAc lectin.
AB  - The human pathogenic protozoan Entamoeba histolytica is a motile cell polarized
      into a front pseudopod and a rear uroid. The amoebic Gal/GalNAc surface lectin is
      a major adhesion molecule composed of an immunodominant 170-kDa heavy subunit,
      mostly extracellular except for a short cytoplasmic tail, and of an extracellular
      light subunit. The binding of multivalent ligands triggers lectin capping and
      recruitment to the uroid. The properties of the Gal/GalNAc lectin and its role in
      amoeba adhesion and uroid polarization are reviewed in the context of the
      molecular mechanisms underlying cell polarization and locomotion.

PMID- 10884616
TI  - From genes to sequences to antibiotics: prospects for future developments from
      microbial genomics.
AB  - The entire genome sequences for a number of microbial organisms have become
      available over the past few years. This knowledge is the beginning point for
      understanding the fundamental principles of bacterial structure and function. The
      prospects for gain in knowledge from genomics are discussed in this report.

PMID- 10884617
TI  - The genetics and biochemistry of isoniazid resistance in mycobacterium
      tuberculosis.
AB  - Although the primary targets of activated isoniazid (INH) are proteins involved
      in the biosynthesis of cell wall mycolic acids, clinical resistance is dominated
      by specific point mutations in katG. Mutations associated with target mutations
      contribute to, but still cannot completely explain, resistance to INH. Despite
      the wealth of genetic information currently available, the molecular mechanism of
      cell death induced by INH remains elusive.

PMID- 10884618
TI  - Kaposi's sarcoma-associated herpesvirus and Kaposi's sarcoma.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is present in all epidemiologic
      forms of Kaposi's sarcoma (KS). The KSHV genome contains several open reading
      frames which are potentially implicated in the development of KS. Some are unique
      to KSHV; others are homologous to cellular genes. The putative role of these
      genes in the genesis of KS is discussed.

PMID- 10884619
TI  - The role of probiotic bacteria in cancer prevention.
AB  - Colorectal cancer is one of the most important causes of cancer morbidity and
      mortality in western countries [1]. A myriad of healthful effects have been
      attributed to the probiotic lactic acid bacteria; perhaps the most controversial
      remains that of anticancer activity. There is no direct experimental evidence for
      cancer suppression in humans as a result of consumption of lactic cultures in
      fermented or unfermented dairy products. However, there is a wealth of indirect
      evidence, based largely on laboratory studies, in the literature and this will be
      summarised in the present paper.

PMID- 10884620
TI  - Epidemiology and pathogenesis of Neisseria meningitidis.
AB  - Neisseria meningitidis, an exclusive pathogen of humans, remains the leading
      worldwide cause of meningitis and fatal sepsis, usually in otherwise healthy
      individuals. In recent years, significant advances have improved our
      understanding of the epidemiology and genetic basis of meningococcal disease and
      led to progress in the development of the next generation of meningococcal
      vaccines. This review summarizes current knowledge of the human susceptibility to
      and the epidemiology and molecular pathogenesis of meningococcal disease.

PMID- 10884621
TI  - Preventing infectious disease with passive immunization.
AB  - Antibodies can prevent infectious diseases by providing passive immune
      protection. Here we review successful clinical trials of passive immunization and
      consider some of the unique qualities monoclonal antibodies are now beginning to
      offer for developing methods for passive immunization against a wide range of
      infectious diseases.

PMID- 10884622
TI  - Microsporidiosis in mammals.
AB  - Microsporidia are small, single-celled, obligately intracellular parasites that
      have caused significant agricultural losses and interference with biomedical
      research. Interest in the microsporidia is growing, as these organisms are
      recognized as agents of opportunistic infections in persons with AIDS and in
      organ transplant recipients. Microsporidiosis is also being recognized in
      children and travelers, and furthermore, concern exists about the potential of
      zoonotic and waterborne transmission of microsporidia to humans. This article
      reviews the basic biology and epidemiology of microsporidiosis in mammals.

PMID- 10884623
TI  - New section editors

PMID- 10884624
TI  - Culturing the exudate of an odontogenic infection--a useful procedure?

PMID- 10884625
TI  - In reply

PMID- 10884626
TI  - Dorsal tongue mass.

PMID- 10884627
TI  - Congestive heart failure.

PMID- 10884628
TI  - Simple cryosurgical treatment of the oral melanotic macule.

PMID- 10884629
TI  - Treatment of melanin-pigmented gingiva and oral mucosa by CO2 laser.

PMID- 10884630
TI  - The relationship between the degree of disk displacement and ability to perform
      disk reduction.
AB  - OBJECTIVE: To evaluate the difference in temporomandibular joint (TMJ) disk
      position between reducible and permanently displaced disks. STUDY DESIGN: We
      found 182 joints with disk displacement (83 with reduction and 99 without
      reduction) that were available for the study. The disk position was estimated by
      using magnetic resonance imaging. RESULTS: There was a statistically significant
      difference between them with the permanently displaced disks being located more
      anteriorly. When a comparison was made in the disks as to which degree of
      displacement was moderate, a difference of disk position at either the medial or
      lateral depth of the TMJ was observed. CONCLUSION: It was suggested that the
      permanently displaced disks are located more anteriorly than the reducible
      displaced disks. When the disk displacement was moderate, disk reduction was
      influenced by less disk displacement at either the medial or lateral part of the
      TMJ.

PMID- 10884631
TI  - Ophthalmologic complications after intraoral local anesthesia with articaine.
AB  - A series of 14 cases of ophthalmologic complications after intraoral anesthesia
      of the posterior superior alveolar nerve is presented. The most commonly
      encountered symptoms were diplopia, mydriasis, palpebral ptosis, and abduction
      difficulties of the affected eye. In all cases, these effects occurred a few
      minutes after injection of the anesthetic, followed by complete resolution
      without sequelae on cessation of the anesthetic effect. The pathogenic mechanism
      underlying such ophthalmologic disorders is discussed in terms of a possible
      diffusion of the anesthetic solution toward the orbital region.

PMID- 10884632
TI  - Neuronal structure of microvascular transplants with and without neuronal
      anastomosis.
AB  - OBJECTIVE: Latissimus dorsi transplants have little neuronal regenerative
      capacity without neuronal anastomosis. Histologic differences between transplants
      with and without neuronal anastomosis and 2 distinct types of neurosurgical
      reanastomosis are highlighted in this study. PATIENTS AND METHODS: Fifty-four
      patients with squamous cell carcinomas of the oral cavity (T4) were treated by
      tumor resection and homolateral neck dissection. The defect was covered with a
      microvascular latissimus dorsi transplant. In 15 patients, no neuronal
      anastomoses were performed. In 21 patients, the thoracodorsal nerves were used
      for microneurosurgical reanastomosis, whereas in 18 patients, the cutaneous
      branches of the intercostal nerves were used for microneurosurgical
      reanastomosis. The transplant was examined during surgery and 9 months after
      surgery by means of a histologic examination of a biopsy specimen. The number of
      fascicles, the degree of fibrosis, and the myelination were examined.
      Furthermore, a neurosensory examination was performed 9 months after surgery.
      RESULTS: Overall, our patients had an average of 12.1 fascicles during surgery.
      After surgery, patients without neuronal anastomosis showed an average of 4.9
      fascicles, patients with nerve anastomosis to the cutaneous branches of the
      intercostal nerve showed an average of 6.2 fascicles, and patients with
      anastomosis to the thoracodorsal nerve showed an average of 9.6 fascicles. In
      cases of nerve anastomosis, a lesser degree of fibrosis was found, together with
      good myelinization. The clinical examination showed the best neurosensory
      function in the transplants with anastomosis to the thoracodorsal nerve and the
      worst function in those without neuronal anastomosis. CONCLUSION: Neuronal
      reanastomosis led to more surviving neuronal structures in the postoperative
      histologic specimen. The highest density of fascicles was found in the well
      vascularized thoracodorsal nerve. The neurosensory function agrees with the
      histologic result.

PMID- 10884633
TI  - Release of metal in vivo from stressed and nonstressed maxillofacial fracture
      plates and screws.
AB  - OBJECTIVES: To analyze the release of metal into the adjacent tissues from
      stressed and nonstressed titanium and stainless steel miniplates and screws.
      STUDY DESIGN: Two miniplates were inserted into the cranial vaults of 12 beagle
      dogs while they were under general endotracheal anesthesia. One miniplate was
      shaped to fit the curvature of the skull (control). Another miniplate, made of
      the same material, was bent in a curve until the midpoint was raised 3 mm above
      the ends. Screws were inserted and tightened until the plate conformed to the
      skull curvature, creating stresses in the system. Four animals (2 each, having
      titanium or stainless steel plates and screws) were killed after 4, 12, and 24
      weeks. Metallosis of adjacent soft tissues was assessed qualitatively. Miniplates
      and screws were removed, and adjacent soft tissue and bone was excised. Titanium,
      iron, chromium, nickel, and aluminum levels were assayed by ultraviolet/visible
      light and atomic absorption spectrophotometry. Nonparametric statistical methods
      were used for data analysis. RESULTS: There was no clear relationship between
      pigmentation of soft tissue adjacent to the miniplates and screws and the
      concentrations of metal present. The data did not demonstrate any consistent
      differences in the concentrations of metallic elements next to stressed and
      nonstressed (control) miniplates and screws of either material. CONCLUSION:
      Stresses arising through poor contouring of miniplates do not appear to influence
      the extent of release of metal into the adjacent tissues.

PMID- 10884634
TI  - Randomized clinical trial of the effectiveness of 3 commonly used mouthwashes to
      treat chemotherapy-induced mucositis.
AB  - OBJECTIVE: To test the effectiveness of 3 mouthwashes used to treat chemotherapy
      induced mucositis. The mouthwashes were as follows: salt and soda, chlorhexidine,
      and "magic" mouthwash (lidocaine, Benadryl, and Maalox). STUDY DESIGN: A
      randomized, double-blind clinical trial was implemented in 23 outpatient and
      office settings. Participants were monitored from the time they developed
      mucositis until cessation of the signs and symptoms of mucositis, or until they
      finished their 12-day supply of mouthwash. All participants followed a prescribed
      oral hygiene program and were randomly assigned a mouthwash. Nurses used the Oral
      Assessment Guide for initial assessment and taught patients how to assess their
      own mouths, then phoned the patients every other day to gather status reports.
      RESULTS: In 142 of 200 patients, there was a cessation of the signs and symptoms
      of mucositis within 12 days. No significant differences in time for the cessation
      of the signs and symptoms were observed among the 3 groups. CONCLUSIONS: Given
      the comparable effectiveness of the mouthwashes, the least costly was salt and
      soda mouthwash.

PMID- 10884635
TI  - Buccal and palatal exostoses: prevalence and concurrence with tori.
AB  - OBJECTIVES: The aims of this study were to investigate the prevalence and
      location of oral exostoses and the concurrence of buccal and palatal exostoses
      with tori. STUDY DESIGN: With clinical inspection and palpation, 960 Thais were
      examined for the presence or absence of torus palatinus (TP), torus mandibularis
      (TM), and exostoses. RESULTS: Of the 960 subjects studied, 26.9% exhibited
      exostoses. Exostoses were more common in the maxilla than in the mandible
      (5.1:1). In addition, most of the exostoses were located on the buccal aspect of
      the jaws. The prevalence of exostoses increased with age (P = .000). Exostoses
      were significantly more common in men than in women (62.4% vs 37.6%, P =.000).
      Exostoses were concurrent with TM more frequently than with TP (36.2% vs 20.6%).
      The highest concurrence of exostoses with tori was observed in subjects who had
      both TP and TM (42.6%). CONCLUSIONS: The occurrence of exostoses is related to
      increasing age. TM and exostoses may share the same causative factors, and
      functional influences may contribute. Our findings lend support to the hypothesis
      that the etiology of exostoses involves an interplay of multifactorial genetic
      and environmental factors.

PMID- 10884636
TI  - Medical hypnosis for temporomandibular disorders: treatment efficacy and medical
      utilization outcome.
AB  - AIM: The aim of this study was to examine the effectiveness of a particular
      behavioral medicine treatment modality, medical hypnosis, on reducing the pain
      symptoms of temporomandibular disorders (TMD). METHODS: Twenty-eight patients who
      were recalcitrant to conservative treatment for TMD participated in a medical
      hypnosis treatment program and completed measures of their pain symptoms on 4
      separate occasions: during wait list, before treatment, after treatment, and at a
      6-month follow-up. In addition, pretreatment and posttreatment medical use were
      examined. RESULTS: Statistical analysis of this open trial suggests that medical
      hypnosis is a potentially valuable treatment modality for TMD. Patients reported
      a significant decrease in pain frequency (F [3, 87] = 14.79, P<.001), pain
      duration (F [3, 87] = 9.56, P<.001), and pain intensity (F [3, 87] = 15.08, P<.
      001), and an increase in daily functioning. Analysis suggests that their symptoms
      did not simply spontaneously improve, and that their treatment gains were
      maintained for 6 months after hypnosis treatment. Further, after hypnosis
      treatment, patients exhibited a significant reduction in medical use. CONCLUSION:
      Medical hypnosis appears to be an effective treatment modality for TMD, in terms
      of reducing both symptoms and medical use.

PMID- 10884637
TI  - Epidermal nevus syndrome with development of a mandibular ameloblastoma.
AB  - Epidermal nevus syndrome (ENS) is a hamartoneoplastic syndrome characterized by
      the association of epidermal nevi with abnormalities in other organ systems. We
      report a 32-year-old woman with ENS that, in addition to cutaneous
      manifestations, showed red plaques on the maxillary and mandibular labial
      alveolar mucosa and a papillomatous lesion of the midline posterior hard palate.
      Radiographic examination of the jaws was noncontributory. Approximately 5 years
      later, a follicular ameloblastoma developed in the mandible. The tumor showed
      duct-like cystic spaces, continuity with the overlying epithelium, and globular
      myxomatous areas in the connective tissue. The palatal lesion was diagnosed as
      papilloma, whereas the maxillary plaques showed nonspecific mucositis. The
      association of ameloblastoma with ENS is discussed. This is the second case of
      ENS associated with ameloblastoma reported in the medical literature.

PMID- 10884638
TI  - Intranodal hemangioma of the oral soft tissues: a case report of a rare entity
      with review of the literature.
AB  - The presentation of a primary vascular tumor in a lymph node is a rare
      occurrence. Only 16 documented cases have been reported to date, with none
      described in the oral soft tissues. This case report presents the first
      occurrence of an intra-nodal hemangioma of the oral soft tissue in an 11-year-old
      girl. A review of the literature is also presented.

PMID- 10884639
TI  - Nerve sheath myxoma (neurothekeoma) in the tongue of a newborn.
AB  - Nerve sheath myxoma is a benign peripheral nerve sheath tumor that rarely occurs
      in the oral cavity; experience with these lesions is therefore limited. The
      lesion described in this report appeared clinically as a gradually enlarging,
      painless growth arising on the tongue of a newborn girl. Microscopically, the
      lesion was characterized by nodules of spindle-shaped cells with abundant myxoid
      stroma. Immunohistochemical studies were consistent with a nerve sheath neoplasm.

PMID- 10884640
TI  - Detection of human alpha-defensin-1, an antimicrobial peptide, in the fluid of
      jaw cysts.
AB  - OBJECTIVE: The purpose of this study was to isolate and to identify an
      antimicrobial peptide, human alpha-defensin-1 (HNP-1) in jaw cyst fluid. STUDY
      DESIGN: We collected jaw cyst fluid from 22 patients with various jaw cysts and
      analyzed the peptide components of them by reversed-phase high-performance liquid
      chromatography (HPLC). HNP-1 in the jaw cyst fluid was identified by the amino
      acid sequence and the molecular weight. The concentration of HNP-1 in the fluid
      of various jaw cysts was quantified by HPLC. RESULTS: HNP-1 in the jaw cyst fluid
      was isolated, purified, and identified. The concentrations of HNP-1 in the jaw
      cyst fluid ranged from 27.0 to 3725.4 microg/mL. CONCLUSION: HNP-1 was detected
      in the fluid of various types of jaw cysts.

PMID- 10884641
TI  - Salivary gland changes in chronic fatigue syndrome: a case-controlled preliminary
      histologic study.
AB  - OBJECTIVE: The purpose of this preliminary study is to compare labial salivary
      gland changes of 11 patients with chronic fatigue syndrome with control subjects.
      STUDY DESIGN: Changes in labial salivary glands were graded from 0 to 3+ for
      acinar dilatation, ductal dilatation, periductal fibrosis, plasmacytic
      infiltrate, lymphocytic infiltrate, mast cell infiltrate, and lymphocytic
      aggregates or foci. RESULTS: Four of the 11 subjects had 2+ to 3+ changes in at
      least 4 of the 7 parameters examined. Only the presence of mast cells was
      statistically significant between the 2 groups. Two of these 4 patients had 1
      lymphocytic focus per 4 mm(2) of tissue. CONCLUSIONS: The salivary gland changes
      in patients with chronic fatigue syndrome show varying degrees of ductal and
      acinar dilatation, periductal fibrosis, lymphoplasmacytic infiltrates, and
      occasional lymphocytic foci, all suggestive of primary gland damage. The one
      parameter that showed statistical significance was the presence of mast cells
      (Fisher exact test, 0.0125).

PMID- 10884642
TI  - Comparison of a controlled injection pressure system with a conventional
      technique.
AB  - OBJECTIVE: The purpose of this study was to compare a device that controls flow
      rate during injection through use of a foot pedal with a conventional atraumatic
      syringe injection technique. We determined the change from preinjection to
      postinjection anxiety, the pain perception, procedure tolerance, and anxiety
      about future injections. STUDY DESIGN: Dental injection anxiety questionnaires
      were completed by 80 endodontic patients immediately before and after
      administration of local anesthetic with the 2 experimental methods. Patients also
      completed visual analog scales to rate their pain perception during injection,
      their rating of the overall experience, and their anticipated anxiety about a
      future dental injection. RESULTS: Patients experienced significantly lower
      overall postinjection anxiety and pain of injection and had significantly more
      positive overall experience ratings with the conventional technique than with the
      controlled-rate procedure. CONCLUSIONS: A conventional atraumatic syringe
      injection technique was superior to a controlled injection pressure system in
      pain perception and procedure tolerance and in reducing postinjection dental
      anxiety.

PMID- 10884643
TI  - Apical periodontitis and related factors in an adult Lithuanian population.
AB  - OBJECTIVES: The objectives of this investigation were to study determinants of
      apical periodontitis among Lithuanians who were 35 to 44 years old and to study
      possible associations between apical periodontitis, relevant general diseases,
      and perceived general health. STUDY DESIGN: Information was collected from a
      randomly selected sample, consisting of 147 individuals from Vilnius, Lithuania.
      Aspects of oral and general health, health-related habits and attitudes, and
      social parameters were used as independent variables, with various aspects of
      apical periodontitis as the dependent variable. Associations were tested by
      regression analysis. RESULTS: Apical periodontitis was highly prevalent in this
      Lithuanian population. Oral health-related variables showed the strongest
      association with apical periodontitis. Decayed and filled teeth scores were found
      to be strongly associated with periapical disease, and sound teeth were strongly
      associated with periapical health. In addition, behavioral variables were found
      to be important disease determinants. CONCLUSIONS: Apical periodontitis appeared
      to be an oral health problem closely related to dental caries. No association
      could be detected between general diseases and apical periodontitis, but an
      association between perceived general health and apical periodontitis was
      demonstrated.

PMID- 10884644
TI  - Magnetic resonance imaging of the temporomandibular joint: interobserver
      agreement in subjective classification of disk status.
AB  - OBJECTIVES: To determine interobserver agreement in interpretation of magnetic
      resonance images of the temporomandibular joint by independent observers and to
      evaluate interobserver agreement within each subjectively assigned category.
      STUDY DESIGN: Sixty magnetic resonance images of adolescent temporomandibular
      joints were randomly drawn for evaluation by 4 observers who had not previously
      worked together. All observers independently classified disk position on sagittal
      magnetic resonance images according to written classification criteria consisting
      of 6 categories. RESULTS: Kappa statistics of agreement show moderate agreement
      among all observers for both medial (95% CI, 0.486-0.622) and lateral (95% CI,
      0.450-0.566) components of the joint. Disk displacement without reduction was the
      category with the greatest agreement among all observers (kappa = 0.914).
      CONCLUSION: Moderate to substantial observer agreement across all defined
      categories of disk status may be achieved among a number of observers when
      standardized classification criteria are used. Interobserver agreement is,
      however, not uniform across all categories of disk position described.

PMID- 10884645
TI  - Discrimination between calcified triticeous cartilage and calcified carotid
      atheroma on panoramic radiography.
AB  - The differential diagnosis of calcified atherosclerotic plaque in the
      extracranial carotid vasculature includes a number of anatomic and pathologic
      radiopacities. Most of these are readily distinguishable on the basis of location
      and morphologic features. The calcified triticeous cartilage, however, can be a
      confounding alternative that is frequently misdiagnosed as a calcified atheroma.
      This paper describes the radiographic differences between these 2 entities,
      enabling clinicians to improve their diagnostic acumen when evaluating cervical
      soft tissue calcifications.

PMID- 10884646
TI  - Evaluation of a training program for detection of carotid artery calcifications
      on panoramic radiographs.
AB  - OBJECTIVE: To evaluate the effectiveness of the American Academy of Oral and
      Maxillofacial Radiology-sponsored training packet for identification of carotid
      artery calcifications on panoramic radiographs. STUDY DESIGN: Two examiners, who
      completed the training (trainees), examined 778 panoramic radiographs. The sample
      included 298 men, with a mean age of 66, and 480 women, with a mean age of 68.
      Findings were compared with those obtained by an oral and maxillofacial
      radiologist. A kappa statistic was used to determine agreement between the 2
      trainees. The positive predictive value (PPV) of the program was estimated by
      comparing the trainees rating of disease status with an expert in case
      identification. RESULTS: Examiners 1 and 2 identified 99 and 78 positive cases,
      respectively. A kappa statistic of 0.87 (95% CI, 0.81-0.92) was obtained,
      indicating good interexaminer agreement. The expert identified 27 positive cases,
      resulting in a PPV of 34.6% (95% CI, 24.4-46.3). CONCLUSION: Although the
      training packet offers valuable training, it does not provide a high PPV,
      suggesting the need to modify it or to seek an expert opinion before
      classification of a patient as having calcification on a panoramic radiograph.

PMID- 10884647
TI  - Temporomandibular joint involvement in a patient with centronuclear myopathy.
AB  - We describe here the temporomandibular joint and masticatory muscle abnormalities
      disclosed by computed tomography and magnetic resonance imaging in a 25-year-old
      man with centronuclear myopathy (a congenital myopathy) who presented with marked
      limitation of jaw movements. We found an intense and general fatty replacement of
      the masticatory muscles, and magnetic resonance imaging signals indicated
      articular fibrosis. We conclude that in centronuclear myopathy, the presence of
      weakness and hypomotility of the masticatory muscles can induce chronic
      abnormalities of the temporomandibular joint.

PMID- 10884648
TI  - Cardiopulmonary bypass exacerbates oxidative stress but does not increase
      proinflammatory cytokine release in patients with diabetes compared with patients
      without diabetes: regulatory effects of exogenous nitric oxide.
AB  - BACKGROUND: Cardiopulmonary bypass induces oxidative stress and a whole-body
      inflammatory reaction that are believed to increase surgical morbidity.
      OBJECTIVES: Our goal was to investigate the effect of nitric oxide
      supplementation on bypass-induced oxidative stress and inflammatory reaction in
      patients with and without diabetes undergoing elective coronary bypass graft
      surgery. METHODS: Patients with and without diabetes were randomized to receive
      an infusion of saline solution or the nitric oxide donor nitroglycerin at 1
      microg. kg(-1). min(-1) starting 10 minutes before the initiation of
      cardiopulmonary bypass and then maintained for 4 hours (n = 10 per group). Serial
      blood samples were taken at various intervals and plasma was analyzed for markers
      of oxidative stress (lipid hydroperoxides, protein carbonyls, and protein
      nitrotyrosine) and inflammation (complement C3a, elastase, interleukin 8, and
      tumor necrosis factor alpha). RESULTS: Cardiopulmonary bypass significantly
      increased lipid hydroperoxides, protein carbonyls, protein nitrotyrosine,
      complement C3a, elastase, soluble E-selectin, interleukin 8, and tumor necrosis
      factor alpha in both groups. Infusion of nitroglycerin significantly reduced the
      increase in lipid hydroperoxides and protein carbonyls in patients who have
      diabetes without affecting levels in patients without diabetes. Nitroglycerin
      infusion markedly reduced protein nitrotyrosine and tumor necrosis factor alpha
      levels in both groups. In contrast, nitroglycerin infusion significantly
      increased C3a in patients without diabetes and increased elastase and interleukin
      8 levels in patients with diabetes. CONCLUSIONS: Cardiopulmonary bypass induces a
      greater oxidative stress in patients with diabetes than in those without
      diabetes, and the inflammatory reaction is qualitatively different in the 2
      groups of patients. In addition, nitroglycerin reduces oxidative stress in
      patients with diabetes and differentially affects the inflammatory response to
      bypass both in patients with and in those without diabetes. The results have
      important implications with respect to the use of nitric oxide donors during
      cardiopulmonary bypass.

PMID- 10884649
TI  - Extracorporeal circulation can induce hypotension by both blood-material contact
      and pump-induced platelet aggregation.
AB  - OBJECTIVE: Use of extracorporeal systems in cardiopulmonary bypass and dialysis
      induces vascular reactions, which can lead to hypotension and lung edema.
      METHODS: To study the contribution of blood-material contact and use of a roller
      pump, as well as prevention of their adverse effects, we perfused a rat hind leg
      with a tube connecting a carotid and a femoral artery. RESULTS: Autoperfusion of
      an uncoated tube caused a fall of aortic pressure and femoral resistance to 66%
      +/- 16% and 76% +/- 15%, respectively, of their initial values within 2 hours,
      whereas in control animals without a shunt, these variables hardly changed (to
      94% +/- 2.8% and 99% +/- 2.8%, respectively). Lung water content became
      significantly higher than that found in control animals (79.4% +/- 1.50% versus
      77. 0% +/- 1.67%). If we coated the tube with albumin, these changes were largely
      prevented. When the coated tube was placed in a roller pump, aortic pressure and
      femoral resistance immediately fell to 79% +/- 17.2% and 63% +/- 13.5%,
      respectively, whereas lung water content did not increase. The vasodilation was
      caused by platelet aggregation and could be prevented with aurintricarboxylic
      acid, which inhibits shear-induced platelet aggregation by blocking the binding
      of von Willebrand factor to platelet glycoprotein Ib receptors. CONCLUSIONS:
      Extracorporeal circulation may induce hypotension and lung edema by means of
      blood-material contact. Hypotension can be prevented by coating the system with
      albumin but can still result from pump-induced platelet aggregation.

PMID- 10884651
TI  - Statistical methods.

PMID- 10884650
TI  - Selective use of extracorporeal membrane oxygenation is warranted after lung
      transplantation.
AB  - OBJECTIVES: Early allograft dysfunction after lung transplantation ranges from
      subclinical x-ray abnormalities to pulmonary edema, hypoxemia, hypercarbia, and
      pulmonary hypertension. Management may include extracorporeal circulation to
      allow recovery of the acute lung injury. We reviewed our experience with
      extracorporeal membrane oxygenation after lung transplantation to assess the
      utility of this therapy. METHODS: A retrospective chart review was performed.
      Single or bilateral lung transplantation was performed in 444 adults from July
      1988 to July 1998. Twelve (2.7%) patients experienced allograft dysfunction
      severe enough to require extracorporeal membrane oxygenation after failure of
      conventional therapy, including sedation, paralysis, and inhaled nitric oxide.
      RESULTS: Seven of 12 patients requiring extracorporeal membrane oxygenation were
      discharged from the hospital. Mean and median times to extracorporeal membrane
      oxygenation support were 1.2 days and 0 days, respectively. Mean length of
      support was 4.2 days. Four patients died while receiving extracorporeal membrane
      oxygenation support. One patient was weaned from extracorporeal membrane
      oxygenation but died during the hospitalization. Two patients required acute
      retransplantation while receiving extracorporeal membrane oxygenation, and one
      survived to discharge. Three patients continued to receive extracorporeal
      membrane oxygenation support for more than 4 days, and all 3 died. All survivors
      had begun receiving extracorporeal membrane oxygenation support by post
      transplantation day 1. Three of 7 patients discharged from the hospital died 12
      months, 13 months, and 72 months after transplantation because of bronchiolitis
      obliterans syndrome (n = 2) or lymphoma (n = 1). Four patients are alive 2, 12,
      25, and 54 months after transplantation. CONCLUSIONS: Extracorporeal membrane
      oxygenation provides effective therapy for acute post-transplantation lung
      dysfunction. The frequency and pattern of our extracorporeal membrane oxygenation
      use reflects bias toward early extracorporeal membrane oxygenation support for
      isolated graft failure in otherwise intact and uninfected recipients.

PMID- 10884652
TI  - The role of antibodies in dysfunction of pig-to-baboon pulmonary transplants.
AB  - OBJECTIVE: Pulmonary transplantation has become the preferred treatment for end
      stage lung disease, but application of the procedure is limited because of a
      paucity of donors. One way to solve donor limitations is to use animal organs as
      a donor source or xenotransplantation. The current barrier to pulmonary
      xenotransplantation is the rapid failure of the pulmonary xenograft. Although
      antibodies are known to play a role in heart and kidney xenograft rejection,
      their involvement in lung dysfunction is less defined. This project was designed
      to define the role of antibodies in pulmonary graft rejection in a pig-to-baboon
      model. METHODS: Orthotopic transgenic swine left lung transplants were performed
      in baboons depleted of antibodies by one of three techniques before
      transplantation: (1) ex vivo swine kidney perfusion, (2) total immunoglobulin
      depleting column perfusion, and (3) ex vivo swine lung perfusion. Results were
      compared with those of transgenic swine lung transplants in unmodified baboons.
      RESULTS: All three techniques of antibody removal resulted in depletion of
      xenoreactive antibodies. Only pretransplantation lung perfusion improved
      pulmonary xenograft function compared with lung transplantation in unmodified
      baboons. CONCLUSIONS: The pathogenesis of pulmonary injury in a swine-to-primate
      transplant model is different from that in renal and cardiac xenografts.
      Depletion of antibodies alone does not have a beneficial effect and may actually
      be detrimental.

PMID- 10884653
TI  - Improvement of rejection-induced diastolic abnormalities in rat cardiac
      allografts with inducible nitric oxide synthase inhibition.
AB  - OBJECTIVE: Inhibition of inducible nitric oxide synthase (nitric oxide II)
      activity has been proposed as a method to attenuate capillary leak and edema
      during rejection of heterotopically transplanted rat hearts. Myocardial edema has
      previously been implicated in diastolic dysfunction during allograft rejection.
      Accordingly, we tested the hypothesis that inducible nitric oxide synthase
      inhibition with aminoguanidine would alleviate left ventricular stiffening and
      myocardial edema formation in 4-day heterotopic rat heart allografts. METHODS:
      Passive left ventricular filling was studied in American Cancer Institute Lewis
      rats receiving heterotopic heart transplants receiving either aminoguanidine, a
      selective nitric oxide synthase inhibitor (n = 6); dexamethasone (1 mg. kg(-1).
      d(-1) administered subcutaneously) for 4 days after transplantation (n = 6); or
      intravenous saline solution (n = 6). American Cancer Institute-to-American Cancer
      Institute isografts (n = 6) were used as controls. RESULTS: Serum nitrite/nitrate
      levels in the aminoguanidine group (18 +/- 3 mmol/L) and dexamethasone group (22
      +/- 4 mmol/L) were reduced versus the intravenous saline group (144 +/- 36 mmol/L
      [SEM]) to levels seen in controls (25 +/- 9 mmol/L). Left ventricular volume at
      15 mm Hg for the aminoguanidine group was increased versus that for the
      intravenous saline solution group, similar to that for controls, and reduced
      versus dexamethasone-treated animals. Myocardial water content for the
      aminoguanidine-treated animals (78.3% +/- 0.4%) was similar to those of
      intravenous saline-treated animals (78.0% +/- 0. 3%) but greater than those of
      controls (77.1% +/- 0.2%) and dexamethasone-treated animals (76.7% +/- 0.3%).
      CONCLUSIONS: Nitric oxide II inhibition with aminoguanidine minimizes the
      reduction in left ventricular filling that is seen with allograft rejection
      through a mechanism that is not associated with attenuation of myocardial edema.

PMID- 10884654
TI  - Reduction of endothelial injury after hypothermic lung preservation by initial
      leukocyte-depleted reperfusion.
AB  - OBJECTIVES: Leukocyte depletion has been shown to ameliorate the effects of
      reperfusion injury in many organ systems. The aim of this study was to
      investigate the effects of leukocyte depletion on functional and endothelial
      markers of pulmonary performance after cold ischemic injury. METHOD: Groups of 6
      rat lungs were flushed with University of Wisconsin solution and then stored at 4
      degrees C for 4 hours. They then underwent sanguine reperfusion for 30 minutes,
      during which time functional measures (gas exchange, pulmonary artery, and airway
      pressures) were made and after which the lungs underwent estimation of
      endothelial permeability by measurement of the capillary filtration coefficient
      (in grams per centimeter of water per minute per grams of wet lung tissue) by a
      gravimetric technique. Four groups were studied: group 1 underwent no
      reperfusion, group 2 underwent 30 minutes of reperfusion, group 3 underwent 30
      minutes of leukocyte-deplete reperfusion with an in-line leukocyte filter (PALL),
      and group 4 underwent 10 minutes of leukocyte-depleting reperfusion followed by
      20 minutes of normal reperfusion. RESULTS: The capillary filtration coefficient
      increased between group 1 and group 2 animals (1.05 +/- 0.32 to 3.07 +/- 0.47
      [mean +/- SEM]; P <.01). Complete leukocyte depletion caused the greatest
      diminution in the capillary filtration coefficient (0.392 +/- 0.07, P <.001), but
      initial leukocyte depletion (group 4) also showed a significant diminution (0.74
      +/- 0.3, P <.01). Complete or initial leukocyte depletion caused no significant
      change in functional measures of pulmonary performance. Complete leukocyte
      depletion produced less pulmonary leukostasis, as assessed by means of
      myeloperoxidase activity. CONCLUSION: Initial and continued leukocyte depletion
      are associated with amelioration of reperfusion-induced endothelial injury after
      cold ischemic injury.

PMID- 10884656
TI  - Commentary.

PMID- 10884655
TI  - Remodeling of the porcine pulmonary autograft wall in the aortic position.
AB  - OBJECTIVE: Dilatation and valve regurgitation are disturbing sequelae of the
      pulmonary root functioning at systemic pressures. We tried to characterize the
      histologic mode of adaptation of the neoaortic wall. METHODS: We compared routine
      histologic studies, immunohistochemical staining, and computer-assisted
      morphometric analysis of aortic, pulmonary autograft, and native pulmonary wall
      specimens from pigs in which, as a newborn, a valveless pulmonary autograft had
      been implanted in the aorta. RESULTS: Histologic examination of the pulmonary
      autograft revealed a viable, normally revascularized wall without degenerative
      phenomena. Smooth muscle cells were enlarged and rearranged. The characteristic
      "pulmonary" medial elastin lamellar structure was retained, which was confirmed
      by morphometry. Immunohistochemistry of the autograft revealed relatively strong
      staining of type III collagen and alpha smooth muscle actin, exclusive staining
      of basic fibroblast growth factor, and no staining of proliferation markers
      proliferating cell nuclear antigen and Ki67. CONCLUSION: The developing pulmonary
      autograft in the aortic position becomes normally revascularized, lacks major
      degenerative phenomena, and retains its own typical pulmonary morphologic
      features. Remodeling is accomplished by increased extracellular matrix deposition
      with collagen as an important constituent. The marked expression of growth
      factors in the autograft suggests the persistence of increased metabolic
      activity.

PMID- 10884657
TI  - Reversible pulmonary trunk banding with a balloon catheter: assessment of rapid
      pulmonary ventricular hypertrophy.
AB  - OBJECTIVE: We sought to assess the rapid hypertrophy of the right ventricle of
      young goats submitted to progressive pressure load by a balloon catheter.
      METHODS: The hearts of 6 young goats were assessed by means of echocardiography
      and cell morphology during and after right ventricular hypertrophy had been
      produced by a balloon catheter. Myocardial samples of the right ventricular
      outflow tract were harvested for microscopic studies. The external diameter of
      longitudinally sectioned myocytes was measured at the nucleus level. The volume
      density of mitochondria was also determined. A balloon catheter was then placed
      through the right ventricular outflow tract in the pulmonary trunk and
      progressively inflated every 2 days. Postoperative serial echocardiography was
      performed at intervals of 1 to 2 days. The animals were killed after 2 to 3 weeks
      of right ventricular training for morphologic analysis. RESULTS: Under optical
      microscopy, there was a 20.5% increase in the mean diameter of the myocyte of the
      trained right ventricle. However, under electron microscopy, there was no
      significant change in the mean volume density of mitochondria from the trained
      right ventricle. Serial echocardiography showed equalization of the ventricular
      thickness over a short interval of 6 to 10 days of progressive balloon inflation.
      CONCLUSIONS: The balloon catheter permits the manipulation of the pressure load
      over the right ventricle, causing rapid hypertrophy in a 6- to 10-day period.
      This study suggests that nonsurgical preparation of the "pulmonary ventricle" in
      patients with transposition of great arteries with intact ventricular septum
      beyond the neonatal period could probably be accomplished within a very few days.

PMID- 10884658
TI  - Serial blood lactate measurements predict early outcome after neonatal repair or
      palliation for complex congenital heart disease.
AB  - OBJECTIVES: Neonates with congenital heart disease may appear hemodynamically
      stable after operation and then suddenly experience catastrophic decompensation.
      An improved means of predicting which infants will suddenly die in the early
      postoperative period may lead to lifesaving interventions. Studies indicate that
      blood lactate level is proportional to tissue oxygen debt, but information
      linking lactate levels with outcome in infants after operation is limited. We
      sought to determine whether a change in lactate level over time was predictive of
      a poor outcome defined as death within the first 72 hours or the need for
      extracorporeal membrane oxygenation. METHODS: To test this hypothesis, we studied
      prospectively 46 infants who were less than 1 month old and were undergoing
      complex cardiac surgical palliation or repair. Postoperative arterial oxygen
      saturation, bicarbonate, and lactate levels were recorded on admission to the
      intensive care unit and every 3 to 12 hours for the first 3 days. RESULTS: Thirty
      seven patients had a good outcome, and 9 patients had a poor outcome. Mean
      initial lactate level was significantly greater in patients with a poor outcome
      (9.4 +/- 3.8 mmol/L) than in patients with a good outcome (5.6 +/- 2.1 mmol/L; P
      =.03). However, an elevated initial lactate level of more than 6 mmol/L had a low
      positive predictive value (38%) for poor outcome. In contrast, a change in
      lactate level of 0.75 mmol/L per hour or more was associated with a poor outcome
      (P <.0001) and predicted a poor outcome with an 89% sensitivity value, a 100%
      specificity value, and a 100% positive predictive value. CONCLUSIONS: Serial
      blood lactate level measurements may be an accurate predictor of death or the
      requirement for extracorporeal membrane oxygenator support for patients who
      undergo complex neonatal cardiac surgery.

PMID- 10884659
TI  - Assessment of pulmonary/systemic blood flow ratio after first-stage palliation
      for hypoplastic left heart syndrome: development of a new index with the use of
      doppler echocardiography.
AB  - OBJECTIVE: Circulatory maldistribution is believed to be a major cause of early
      death after first-stage palliation for hypoplastic left heart syndrome. Flow
      reversal in the reconstructed aorta may reflect the pulmonary/systemic blood flow
      ratio. The purpose of our study was to investigate the utility of arterial PO
      (2), arterial oxygen saturation, and a newly developed Doppler-derived flow index
      in predicting the pulmonary/systemic flow ratio after first-stage palliation for
      hypoplastic left heart syndrome. METHODS: Twenty-four infants who underwent first
      stage palliation for hypoplastic left heart syndrome or a variant were studied.
      Superior vena cava blood samples were drawn to estimate the mixed venous
      saturation and permit calculation of the pulmonary/systemic blood flow ratio.
      Fifty-four samples were evaluated within the first 24 hours after surgery.
      Simultaneous blood draw and Doppler echocardiography were performed with
      interrogation in the distal aspect of the arch reconstruction. The ratio of the
      Doppler velocity-time integral of retrograde flow to the velocity-time integral
      of forward flow was calculated and compared with the pulmonary/systemic blood
      flow ratio RESULTS: The median mixed venous saturation for the 54 samples was low
      (38.5%; range, 18%-64%). The median calculated pulmonary/systemic blood flow
      ratio was 1.4:1 (range, 0.3:1 to 4. 2:1). Pulse pressure, mixed venous
      saturation, and arterial PO (2) were not statistically significant predictors of
      the measured pulmonary/systemic blood flow ratio. Although both aortic oxygen
      saturation (R (2) = 0.84, P <.01) and Doppler flow reversal ratio (R (2) = 0.94,
      P <.001) were significantly associated with the measured pulmonary/systemic blood
      flow ratio, the model coefficient of determination was greatest for Doppler flow
      reversal ratio. CONCLUSION: Measures of arterial oxygen saturation and arterial
      PO (2) may be misleading in assessing the circulatory status of infants after
      first-stage palliation for hypoplastic left heart syndrome. Doppler
      echocardiography, through use of the Doppler flow reversal ratio, provides a more
      useful measure of pulmonary/systemic blood flow ratio. Low mixed venous
      saturation after surgery may be due to factors other than pulmonary
      overcirculation, such as ventricular dysfunction and low cardiac output.

PMID- 10884661
TI  - Single versus bilateral lung transplantation for idiopathic pulmonary fibrosis: a
      ten-year institutional experience.
AB  - OBJECTIVE: Between July 1988 and July 1998, we performed 433 lung transplants.
      Forty-five patients had idiopathic pulmonary fibrosis, and operations for these
      patients included 32 single lung transplants and 13 bilateral sequential lung
      transplants. This study reviews this experience and compares single lung
      transplantation and bilateral lung transplantation for pulmonary fibrosis.
      METHODS: We performed a retrospective review, including inpatient hospital
      charts, outpatient clinic records, and telephone contact with patients to verify
      current health status. RESULTS: Perioperative mortality was 4 (8.9%) patients.
      One patient underwent redo bilateral lung transplantation for reperfusion injury
      and graft failure after single lung transplantation. The median hospitalization
      was 22 days. Actuarial survival at 1 and 5 years was 75.5% and 53.5%,
      respectively, which was not significantly different from our survival for all
      recipients (85.5% and 56.4%, respectively). Seventeen (41%) of 41 operative
      survivors have died. Late causes of death included obliterative bronchiolitis
      with respiratory failure (9), malignancy (3), and cytomegalovirus pneumonitis
      (2). Hospital mortality was 3 (9.4%) of 32 after single lung transplantation and
      1 (7.7%) of 13 after bilateral lung transplantation. There was no difference
      between single and bilateral lung transplantation with regard to hospital stay.
      Four (12.5%) of the 32 patients undergoing single lung transplantation required
      tracheostomy, whereas 3 (23%) of 13 recipients undergoing bilateral lung
      transplantation required tracheostomy. CONCLUSION: Single or bilateral lung
      transplantations offer viable therapy for patients with pulmonary fibrosis. We
      demonstrate no benefit of bilateral over single lung transplantation for patients
      with this diagnosis. Survival after transplantation appears better than that of
      historic control subjects receiving standard medical care at other institutions.

PMID- 10884660
TI  - Systemic lobar shunting induces advanced pulmonary vasculopathy.
AB  - OBJECTIVES: We characterized the morphology and vasomotor responses of a
      localized, high-flow model of pulmonary hypertension. METHODS: An end-to-side
      anastomosis was created between the left lower lobe pulmonary artery and the
      aorta in 23 piglets. Control animals had a thoracotomy alone or did not have an
      operation. Eight weeks later, hemodynamic measurements were made. Then shunted
      and/or nonshunted lobes were removed for determination of vascular resistance and
      compliance by occlusion techniques under conditions of normoxia, hypoxia (FIO (2)
      = 0.03), and inspired nitric oxide administration. Quantitative histologic
      studies of vessel morphology were performed. RESULTS: Eighty-three percent of
      animals having a shunt survived to final study. Aortic pressure, main pulmonary
      artery and wedge pressures, cardiac output, blood gases, and weight gain were not
      different between control pigs and those receiving a shunt. Six of 9 shunted
      lobes demonstrated systemic levels of pulmonary hypertension in vivo. Arterial
      resistance was higher (24.3 +/- 12.0 vs 1.3 +/- 0. 2 mm Hg. mL(-1). s(-1), P
      =.04) and arterial compliance was lower (0. 05 +/- 0.01 vs 0.16 +/- 0.03 mL/mm
      Hg, P =.02) in shunted compared with nonshunted lobes. Hypoxic vasoconstriction
      was blunted in shunted lobes compared with nonshunted lobes (31% +/- 13% vs 452%
      +/- 107% change in arterial resistance, during hypoxia, P <.001). Vasodilation to
      inspired nitric oxide was evident only in shunted lobes (34% +/- 6% vs 1.8% +/-
      8.2% change in arterial resistance during administration of inspired nitric
      oxide, P =.008). Neointimal and medial proliferation was found in shunted lobes
      with approximately a 10-fold increase in wall/luminal area ratio. CONCLUSIONS: An
      aorta-lobar pulmonary artery shunt produces striking vasculopathy. The
      development of severe pulmonary hypertension within a short time frame, low
      mortality, and localized nature of the vasculopathy make this model highly
      attractive for investigation of mechanisms that underlie pulmonary hypertension.

PMID- 10884662
TI  - Immunosuppressant-free allotransplantation of the trachea: the antigenicity of
      tracheal grafts can be reduced by removing the epithelium and mixed glands from
      the graft by detergent treatment.
AB  - OBJECTIVE: To develop a method for eliminating the epithelium and mixed glands
      from tracheal grafts by detergent treatment and evaluate these grafts for
      immunosuppressant-free allotransplantation in dogs. METHODS: Fresh canine
      tracheal grafts were treated with a detergent (1% Triton X-100 t
      octylphenoxypolyethoxyethanol; T-9284; Sigma Chemical Co, St Louis, Mo) at 4
      degrees C for 48 hours. The grafts were then used for intrathoracic 5-ring
      tracheal replacement in other dogs without immunosuppressant treatment (n = 6,
      detergent treatment group). In the control group (n = 6) fresh untreated canine
      tracheal segments were implanted as allografts. All the implanted grafts were
      covered with an omental pedicle. RESULTS: In the detergent treatment group the
      chondrocytes in the graft had a similar appearance to those in the fresh trachea,
      indicating that the chondrocytes remained viable after the detergent treatment.
      In 5 of the 6 grafts, the epithelium and mixed glands had been removed
      completely. After transplantation, these 5 grafts were incorporated by the host
      trachea without stenosis. In the remaining treated tracheal graft, in which
      removal of the epithelium was incomplete, moderate stenosis was observed at the
      fourth week after implantation, although this was not progressive. In the control
      group, granulation tissue of the graft and significant stenosis were observed
      after transplantation. CONCLUSION: The antigenicity of tracheal grafts can be
      greatly reduced by removing the epithelium and mixed glands by the use of
      detergent treatment. The epithelium and mixed glands of the graft appear to be
      the determining elements involved in rejection after tracheal
      allotransplantation.

PMID- 10884663
TI  - Surgical approaches to membranous tracheal wall lacerations.
AB  - BACKGROUND: Smaller postintubation tracheal tears are often misdiagnosed and,
      when recognized, they are effectively managed in a conservative fashion. Large
      membranous lacerations, especially if associated with important manifestations,
      require immediate surgical repair. We report our experience over the past 7
      years. METHODS: From 1993 to 1999, 11 patients with a postintubation posterior
      tracheal wall laceration were treated in our institution. One patient was male
      and 10 were female, with a mean age of 68 years. Ten patients underwent
      orotracheal intubation under general anesthesia for elective surgery, 4 of whom
      were treated with a double-lumen selective tube. One patient underwent emergency
      intubation because of anaphylactic shock. In 9 cases the tracheal tear was
      promptly repaired, by way of a thoracotomy in 4 and by way of a cervicotomy and
      longitudinal tracheotomy in 5. In 2 cases the tear was small and was consequently
      managed conservatively. RESULTS: All surgical procedures proved effective in
      repairing the laceration, and there was no mortality or morbidity in the
      perioperative period. Early and late endoscopic follow-up showed no signs of
      tracheobronchial stenosis. CONCLUSIONS: When repair of membranous tracheal
      laceration is required, the surgical approach should be through a thoracotomy if
      the tear involves the distal trachea, a main stem, or both, and through a
      cervicotomy when the laceration is located in the proximal two thirds of the
      trachea. Performing a longitudinal tracheotomy to reach and suture the posterior
      tracheal wall is a reliable, quick, and safe procedure, and it avoids lateral and
      posterior dissection of the trachea.

PMID- 10884664
TI  - Bronchoplastic procedures in malignant and nonmalignant disease: multivariable
      analysis of 144 cases.
AB  - OBJECTIVES: We sought to analyze the experience with bronchoplastic procedures
      over a 7-year period and to determine putative prognostic factors for survival.
      METHODS: From 1991 to 1997, 144 bronchoplastic procedures were performed for non
      small cell lung cancer (n = 123), small cell lung cancer (n = 5), carcinoid tumor
      (n = 10), and metastases of extrathoracic malignant tumors (n = 6). There were
      111 sleeve lobectomies, 17 bilobectomies, 4 lobectomies with carinal resection, 8
      sleeve pneumonectomies, and 4 bronchotomies without parenchymal resection.
      Multivariable analysis included risk factors, such as age, sex, type of
      bronchoplastic procedure (bronchotomy, lobectomy, bilobectomy, or pneumonectomy),
      additional angioplasty, TNM staging, histology, radicality of resection,
      respiratory risk (forced expiratory volume in 1 second, percent predicted < 60),
      cardiovascular risk, and adjuvant therapy. RESULTS: Overall 1- and 3-year
      survival was 72% and 52%, respectively. The overall 30-day mortality was 8.3%
      (5.4% for single sleeve lobectomies). Multivariable analysis demonstrated 4 risk
      factors for survival. High tumor stage, type of bronchoplastic procedure,
      impaired lung function, and presence of cardiovascular risk were associated with
      a poor outcome. Univariate analysis showed reduced survival in patients with
      sleeve pneumonectomies (1-year survival, 25%). CONCLUSIONS: Bronchoplastic
      procedures for central tumors and sleeve pneumonectomies are associated with poor
      survival. Careful selection of these patients, as well as of patients with
      impaired lung function and cardiovascular risk factors, is mandatory.

PMID- 10884665
TI  - Positron emission tomography with f18-fluorodeoxyglucose in the staging and
      preoperative evaluation of malignant pleural mesothelioma.
AB  - OBJECTIVES: The purpose of this study was to evaluate the utility of positron
      emission tomography with F18-fluorodeoxyglucose in the preoperative evaluation
      and staging of malignant mesothelioma in patients who were candidates for
      aggressive combined modality therapy. METHODS: Eighteen consecutive patients with
      biopsy-proven malignant mesothelioma underwent positron emission tomographic
      scanning. The results of positron emission tomographic imaging were compared with
      results obtained by computed tomography, mediastinoscopy, thoracoscopy, and
      pathologic examination of surgical specimens. All patients fasted and received an
      average of 14.5 +/- 2.7 mCi of F18-fluorodeoxyglucose for positron emission
      tomographic scanning. Attenuation-corrected whole-body and regional emission
      images of the chest and upper abdomen were acquired and formatted into
      transaxial, coronal, and sagittal images. RESULTS: All primary malignant
      mesotheliomas accumulated F18-fluorodeoxyglucose, and the mean standardized
      uptake value was 7. 6 (range, 3.33-14.85; n = 9). There were no false-negative
      results of positron emission tomography. Identification of occult extrathoracic
      metastases by positron emission tomography was the basis for excluding two
      patients from surgical therapy. There were two false-positive results of positron
      emission tomography: increased F18-fluorodeoxyglucose uptake in the contralateral
      chest that was negative by thoracoscopic biopsy (n = 1) and increased abdominal
      F18-fluorodeoxyglucose uptake after partial colectomy for diverticular disease (n
      = 1). CONCLUSIONS: Positron emission tomography can identify malignant pleural
      mesothelioma and appears to be a useful noninvasive staging modality for patients
      being considered for aggressive combined modality therapy.

PMID- 10884666
TI  - Clinical experience with autologous endothelial cell-seeded
      polytetrafluoroethylene coronary artery bypass grafts.
AB  - OBJECTIVE: Autologous endothelial cell seeding was used to improve the patency of
      4-mm polytetrafluoroethylene vascular prostheses. METHODS: Since 1995, 14
      patients with coronary artery disease received 21 autologous endothelial cell
      seeded polytetrafluoroethylene vascular bypass grafts for coronary artery
      revascularization. The polytetrafluoroethylene grafts were seeded with the
      endothelial cells in a multiple step procedure, including cell culture techniques
      before coronary bypass operation. With the use of extracorporal circulation and
      cardioplegic arrest, a bypass operation was performed by means of conventional
      surgical techniques. RESULTS: After a mean postoperative follow-up of 27.7 months
      (range, 7.5-48 months), the graft patency rate is 90.5%. Follow-up angiograms of
      the aorta-coronary polytetrafluoroethylene bypass grafts showed patent bypasses
      in all cases except two. Angiograms of all 19 patent endothelial cell-seeded
      polytetrafluoroethylene bypass grafts showed a smooth luminal borderline without
      stenotic regions. The percutaneous transluminal angioscopic evaluation showed a
      glossy white and smooth endoluminal graft surface without any fibrin, platelet,
      or erythrocyte deposits. Intravascular ultrasonographic examinations confirmed
      the results. CONCLUSION: Patency of autologous endothelial cell-seeded 4-mm
      polytetrafluoroethylene vascular prostheses as coronary artery bypass grafts was
      much better than that of unseeded polytetrafluoroethylene grafts. Further
      evaluations and a larger population of patients will prove whether the
      encouraging patency will last.

PMID- 10884667
TI  - Obstruction of St Jude Medical valves in the aortic position: significance of a
      combination of cineradiography and echocardiography.
AB  - BACKGROUND: Obstruction of the St Jude Medical valve (St Jude Medical, Inc, St
      Paul, Minn) is a rare but serious complication. METHODS: Cineradiographic and
      echocardiographic evaluations of aortic St Jude Medical valves were
      simultaneously performed on 54 patients, with no signs of prosthetic valve
      dysfunction late after surgery. RESULTS: Although closing angles of the leaflets
      corresponded closely with the manufacturer data, restricted opening of the
      leaflets (opening angle >/= 20 degrees ) was found in 16 (group D) of the 54
      patients by means of cineradiography. The opening angles were equal to or less
      than 14 degrees in the other 23 patients (group N) and between 15 degrees and 19
      degrees in the remaining 15 (group M). Doppler-derived transprosthetic pressure
      gradients were significantly higher (P =.03) and the velocity index was
      significantly lower (P =.003) in group D than in group N. However, no significant
      differences were found in those values between group N and group M. Replacement
      of the aortic St Jude Medical valves was performed in 5 of the 16 patients, and
      the remaining 11 have been followed up because of relatively low pressure
      gradients. The cause of restricted leaflet movement was pannus formation without
      thrombosis in 4 patients and valve thrombosis with pannus formation in one.
      CONCLUSIONS: Reduced valve orifice area and restricted opening of the leaflets
      resulting from excess growth of pannus probably led to obstruction of the aortic
      St Jude Medical valves. A combination of cineradiography and echocardiography
      makes it possible to provide an accurate and detailed diagnosis of obstruction of
      the valve.

PMID- 10884668
TI  - Pulmonary homograft: should it be used in the aortic position?
AB  - OBJECTIVE: Retrospective analysis was performed to determine the suitability of
      pulmonary homograft as an aortic valve substitute. METHODS: From January 1994
      through June 1999, 147 patients (mean age, 32.2 +/- 17.3 years) underwent aortic
      valve replacement with either an aortic homograft (group 1: n = 103, 25 fresh
      antibiotic preserved and 78 cryopreserved) or a pulmonary homograft (group 2: n =
      44, 11 antibiotic preserved and 33 cryopreserved). In group 1 a scalloped
      subcoronary technique was used in 64 patients, and a root replacement technique
      was used in 39 patients. In group 2 the scalloped subcoronary technique was used
      in 34 patients, and the root replacement technique was used in 10 patients.
      RESULTS: There were 131 operative survivors (group 1 = 91; group 2 = 40). Follow
      up ranged from 2 to 62 months. In group 1 none of the patients had significant
      aortic regurgitation during the hospital stay. Three patients (all having
      undergone the scalloped subcoronary technique) had moderate aortic regurgitation
      after 6 to 32 months. In group 2, 10 patients (9 having undergone the scalloped
      subcoronary technique and 1 having undergone the root replacement technique)
      developed significant regurgitation: 2 intraoperatively, 5 in the early
      postoperative period before discharge from the hospital, and 3 during late follow
      up 6 to 12 months postoperatively. Among the various risk factors analyzed for
      overall homograft failure, use of a pulmonary homograft was the single
      independent predictor of valve failure (odds ratio, 8.6; 95% confidence interval,
      1.9-39; P =.006). CONCLUSION: Pulmonary homograft, when inserted by means of a
      scalloped subcoronary technique, is not a suitable aortic valve substitute.

PMID- 10884669
TI  - The changing pattern of reoperative coronary surgery: trends in 1230 consecutive
      reoperations.
AB  - OBJECTIVE: We noted an increasing risk profile of patients undergoing reoperative
      coronary surgery. We evaluated the risk compared with primary procedures, our
      results over a 16-year span, and the predictors of hospital outcomes after redo
      surgery. METHODS: We analyzed 20,614 patients undergoing isolated coronary
      surgery at our institution from 1982 to 1997. Of these, 1230 (6.0%) were
      undergoing reoperation. Independent predictors of outcomes were identified by
      multivariable regression. RESULTS: The prevalence of reoperation peaked in 1994
      at 8.2%. Patients undergoing reoperation were more likely to be male, to have
      left ventricular dysfunction and worse symptoms, and to require an urgent
      operation than patients undergoing a primary operation (P <.0001). Perioperative
      myocardial infarctions (3.7% vs 7.4%), low-output syndrome (9.0% vs 24.0%), and
      death (2.4% vs 6.8%) were more common in patients undergoing reoperation (all P
      <.0001). Over the years, the risk profile of patients undergoing reoperation
      increased. Age, left ventricular dysfunction, severity of symptoms, extent of
      coronary artery disease, left main stenosis, and requirement for urgent or
      emergency operations increased with time (P <.05). However, mortality, myocardial
      infarction, and low-output syndrome have remained constant. The independent
      predictors of mortality after reoperative surgery were increased age, greater
      Canadian Cardiovascular Society symptom class, earlier year of operation, and
      greater left ventricular dysfunction. After 1990, analysis of an expanded data
      set also identified peripheral vascular disease and failure to use retrograde
      cardioplegia as predictors of mortality. CONCLUSIONS: Improving results of
      reoperative surgery have been offset by an increasing patient risk profile.
      Meticulous operative technique and retrograde cardioplegia may permit good
      results in these high-risk patients.

PMID- 10884670
TI  - In vivo and in vitro study of radio-frequency application with a new long linear
      probe: implication for the maze operation.
AB  - BACKGROUND: The maze operation for atrial fibrillation is effective but highly
      invasive. We tested, both in vitro and in vivo, a new technique for creating long
      linear atrial lesions with a custom-made, 25-mm long, stainless-steel, linear
      probe and a corresponding 500-kHz generator for assistance in the maze operation.
      METHODS: In the in vitro study with the isolated canine atria, the power of the
      delivered radio-frequency energy and the saline irrigating flow rate were changed
      independently, and the sizes of the lesions were measured. In the in vivo study
      radio-frequency energy was delivered to 4 portions (ie, the smooth and
      trabeculated portions of the right and left atria). The sizes of the lesions were
      measured, and the histologic features of the lesions were examined. Electrical
      isolation of the right atrial appendage from the remaining right atrium was
      attempted by using this linear probe. RESULTS: In the in vitro study the size of
      the lesion became larger as the delivered power was increased, although the
      lesion was limited when the flow rate was high. In the in vivo study the size of
      the lesion was equal at the 4 different sites. Histologic examinations
      demonstrated linear and transmural lesions, and electrophysiologic examinations
      revealed conduction block between the right atrial appendage and the remaining
      right atrium. CONCLUSIONS: The new original long linear probe was effective for
      creating transmural linear atrial lesions with the irrigation method, presenting
      the possibility of an intraoperative technique that mimics the maze procedure.

PMID- 10884671
TI  - Isolated bypass grafting of the left internal thoracic artery to the left
      anterior descending coronary artery: late consequences of incomplete
      revascularization.
AB  - OBJECTIVE: Multiple strategies to achieve some degree of myocardial
      revascularization are available. In some, less complete revascularization is
      accepted to limit invasiveness. To examine the issues of incomplete
      revascularization, we assessed the long-term impact of additional non-left
      anterior descending coronary artery stenoses in patients undergoing only grafting
      of the left internal thoracic artery to the left anterior descending coronary
      artery. METHODS: A total of 2067 patients underwent primary isolated grafting of
      the left internal thoracic artery to the left anterior descending coronary artery
      from 1971 to 1997. Of these, 26% and 13% had 2- and 3-system disease,
      respectively. Multivariable analyses of survival and reintervention were
      performed in the hazard function domain for 27,683 patient-years of follow-up
      (mean 14 +/- 6.7). RESULTS: Survival was 99%, 88%, and 62% at 1, 10, and 20
      years. Right coronary artery or left circumflex system disease of 50% or more (P
      =.02) and particularly high-grade (>/=70%) left circumflex (P =.01) and proximal
      right coronary artery disease (P =.01), as well as any degree of left main trunk
      stenosis (P <.0001), were associated with reduced long-term survival. Compared
      with 75% 20-year survival in patients with no non-left anterior descending
      disease, those with either left circumflex or left main trunk disease experienced
      a 44% survival, and those with proximal right coronary artery disease, 42%. The
      most common stated reason for incomplete revascularization was small vessel size.
      Freedom from reintervention was 89% and 65% at 10 and 20 years, respectively.
      High-grade left main trunk disease, but, in contrast, mid or distal disease of
      the right coronary artery, and not left circumflex disease, were risk factors for
      reintervention. CONCLUSIONS: These findings call into question the long-term
      appropriateness of interventions whose strategy includes leaving unrevascularized
      segments in territories not in the distribution of the left anterior descending
      coronary artery.

PMID- 10884672
TI  - Cerebral infarction in children due to thromboembolism from ligated blalock
      taussig shunt.

PMID- 10884673
TI  - Clinical-pathologic conference in thoracic surgery: basaloid squamous carcinoma
      of the trachea.

PMID- 10884674
TI  - Studies in thoracic aortic graft infections: the development of a porcine model
      and a comparison of collagen-impregnated dacron grafts and cryopreserved
      allografts.

PMID- 10884676
TI  - Why antisense technology makes good sense for cancer treatment.

PMID- 10884675
TI  - Studies in thoracic aortic graft infections: the development of a porcine model
      and a comparison of collagen-impregnated dacron grafts and cryopreserved
      allografts.

PMID- 10884677
TI  - New European rules on orphan drugs.

PMID- 10884678
TI  - Formulation and technology aspects of conrolled drug delivery in animals.
AB  - In the veterinary field, the development of new routes of administration or new
      delivery systems capable of controlling the release of drugs are of considerable
      interest. Because of the large number of food-producing animals and the unique
      problems associated with the administration of drugs to these animals, the
      potential markets are huge and will only be fully realized if improvements to old
      dosage forms lead to practical and effective formulations. This review intends to
      summarize the state of the art in the field of veterinary controlled and/or
      prolonged release systems.

PMID- 10884679
TI  - The use of PAMAM dendrimers in the efficient transfer of genetic material into
      cells.
AB  - Polyamidoamine (PAMAM) dendrimers have steadily grown in popularity in the past
      decade in a variety of disciplines, ranging from materials science to
      biomedicine. This can be attributed in part to their use in applications that
      range from computer toners to medical diagnostics. PAMAM dendrimers are safe and
      nonimmunogenic, and can function as highly efficient cationic polymer vectors for
      delivering genetic material into cells. They have been shown to be as efficient
      or more efficient than either cationic liposomes or other cationic polymers (e.g.
      polyethylenimine, polylysine) for in vitro gene transfer. This article will focus
      on the application of PAMAM dendrimers as a nonviral gene delivery vector from
      the initial discovery of this capacity to the most recent experimental findings.

PMID- 10884680
TI  - Latest advances in the development of dry powder inhalers.
AB  - The current market for dry powder inhalers (DPIs) has over 20 devices in present
      use and at least another 30 under development. Clinicians recognize that DPIs are
      a suitable alternative to pressurized metered dose inhalers (pMDIs) for some
      patients but the relative performance of devices is often unclear. The problem is
      compounded by the need to reformulate pMDIs with new propellants, introducing
      further products to the market with associated variations in performance. This
      article reviews the DPIs currently available, the driving forces governing new
      designs, and the claimed advantages of DPIs in the development pipeline.

PMID- 10884681
TI  - Monitor: progress and profiles.
AB  - Monitor provides an insight into the latest developments in pharmaceutical
      science and technology through brief synopses of recent presentations,
      publications and patents, and expert commentaries on the latest technologies.
      There are two sections: Progress summarizes the latest developments in
      pharmaceutical process technology, formulation, analytical technology,
      sterilization, controlled drug delivery systems and regulatory issues; Profiles
      offers expert commentary on emerging technologies, novel processes and strategic,
      organizational and logistic issues underlying pharmaceutical R&D.

PMID- 10884682
TI  - A new direction for myosin.
AB  - Members of the myosin superfamily of actin-based motor proteins were previously
      thought to move only towards the barbed end of the actin filament. In an
      extraordinary reversal of this dogma, an abundant and widespread unconventional
      myosin known as myosin VI has recently been shown to move towards the pointed end
      of the actin filament - the opposite direction of all other characterized
      myosins. This discovery raises novel and intriguing questions about the molecular
      mechanisms of reversal and the biological roles of this 'backwards' myosin.

PMID- 10884683
TI  - Regulated secretion of conventional lysosomes.
AB  - Regulated secretion has been traditionally regarded as a specialized process
      present in only a few cell types. Similarly, the secretory lysosomes of
      hematopoietic cells have been viewed as 'modified' organelles that acquired the
      machinery for regulated exocytosis. However, there is evidence that conventional
      lysosomes can, in many cell types, respond to rises in the intracellular free
      Ca2+ concentration by fusing with the plasma membrane. These findings profoundly
      change the current view of lysosomes as a 'final' station of the endocytic
      pathway and suggest a previously unsuspected active role for this organelle.

PMID- 10884684
TI  - Calmodulin: a prototypical calcium sensor.
AB  - Calmodulin is the best studied and prototypical example of the E-F-hand family of
      Ca2+-sensing proteins. Changes in intracellular Ca2+ concentration regulate
      calmodulin in three distinct ways. First, at the cellular level, by directing its
      subcellular distribution. Second, at the molecular level, by promoting different
      modes of association with many target proteins. Third, by directing a variety of
      conformational states in calmodulin that result in target-specific activation.
      The calmodulin-dependent regulation of protein kinases illustrates the potential
      mechanisms by which Ca2+-sensing proteins can recognize and generate affinity and
      specificity for effectors in a Ca2+-dependent manner.

PMID- 10884685
TI  - Spindle pole body duplication: a model for centrosome duplication?
AB  - The yeast spindle pole body (SPB) is the functional equivalent of the centrosome
      and forms the two poles of the mitotic spindle. Before mitosis, both SPBs and
      centrosomes are present as single copies and must be duplicated to form the
      bipolar spindle. SPB components have been identified using a combination of
      biochemistry and genetics, and their role during SPB duplication has been
      analysed using temperature-sensitive mutants. In this article, we describe
      structural aspects of SPB duplication and their possible relationship to
      centrosome duplication.

PMID- 10884686
TI  - Ubiquitin and its kin: how close are the family ties?
AB  - Modification of proteins by the covalent attachment of ubiquitin is known to
      target them for degradation by proteasomes. Several proteins have been discovered
      recently that are related to ubiquitin or function similarly. Some of these
      proteins act as modifiers; others bear ubiquitin-like domains embedded in their
      polypeptide chain but do not form conjugates with cellular proteins. Ubiquitin
      like proteins mediate an impressive range of cellular functions, including cell
      cycle progression, DNA repair and apoptosis. Recent discoveries endorse the view
      that, in many cases, the function of the relatives of ubiquitin is linked to the
      ubiquitin pathway.

PMID- 10884687
TI  - Growth factor receptor signalling: location, location, location.
AB  - Ligand binding to plasma membrane receptors initiates a series of events
      culminating in a variety of changes in cellular phenotypes. Although numerous
      publications have documented the activation/inactivation of signalling molecules
      following receptor binding, relatively few investigations have focused on the
      cellular compartment responsible for either initiating or selecting the
      particular pathway that mediates the response. Specifically, does receptor
      signalling occur only at the plasma membrane; is signalling dependent upon the
      location of defined endosome populations; or are components of both plasma
      membrane and endosomal activity operative depending upon the particular
      signalling pathway or cell type? This review addresses aspects of these questions
      by discussing the evidence supporting or contrasting the interplay between the
      endocytic and signalling systems for a subset of tyrosine kinase,
      serine/threonine kinase and G-protein-coupled receptors.

PMID- 10884689
TI  - Careers-perspective interview.

PMID- 10884688
TI  - Visualizing membrane traffic in vivo by combined video fluorescence and 3D
      electron microscopy.
AB  - In studies of dynamic cellular processes, it would be ideal to be able to combine
      the capability of in vivo fluorescence video microscopy with the power of
      resolution of electron microscopy (EM). This article describes an approach based
      on the association of these two techniques, by which an individual intracellular
      structure can be monitored in vivo, typically through the use of markers fused
      with green-fluorescent protein, and then analysed by EM and three-dimensional
      reconstruction methods, resulting in a 'snapshot' of its fine structure at any
      chosen time in its life cycle. The potential of this approach is discussed in
      relation to various aspects of cell biology and especially to the question of the
      morpho-functional organization of the intracellular membrane trafficking
      pathways.

PMID- 10884690
TI  - Challenges to the 'new' rangeland science.

PMID- 10884692
TI  - Natural selection in the wild.

PMID- 10884691
TI  - Biological objects, units of selection and character decomposition.

PMID- 10884693
TI  - The future of evolution.

PMID- 10884694
TI  - Areas, cradles and museums: the latitudinal gradient in species richness.
AB  - Although numerous factors are postulated to be responsible for the gradient of
      increasing taxon richness towards lower latitudes, it has recently been suggested
      that the primary determinant is geographic area. This area model is appealing in
      its logic, but there is little empirical evidence to support it and several other
      mechanisms might also interact to obscure its effects. Nonetheless, the model has
      highlighted several fundamental issues concerning range size, speciation and
      extinction that, despite their considerable significance, remain poorly
      understood.

PMID- 10884695
TI  - Eradication revisited: dealing with exotic species.
AB  - Invasions of nonindigenous species threaten native biodiversity, ecosystem
      functioning, animal and plant health, and human economies. The best solution is
      to prevent the introduction of exotic organisms but, once introduced, eradication
      might be feasible. The potential ecological and social ramifications of
      eradication projects make them controversial; however, these programs provide
      unique opportunities for experimental ecological studies. Deciding whether to
      attempt eradication is not simple and alternative approaches might be preferable
      in some situations.

PMID- 10884696
TI  - Lifestyle evolution in symbiotic bacteria: insights from genomics.
AB  - Bacteria that live only in eukaryotic cells and tissues, including chronic
      pathogens and mutualistic bacteriocyte associates, often possess a distinctive
      set of genomic traits, including reduced genome size, biased nucleotide base
      composition and fast polypeptide evolution. These phylogenetically diverse
      bacteria have lost certain functional categories of genes, including DNA repair
      genes, which affect mutational patterns. However, pathogens and mutualistic
      symbionts retain loci that underlie their unique interaction types, such as genes
      enabling nutrient provisioning by mutualistic bacteria-inhabiting animals. Recent
      genomic studies suggest that many of these bacteria are irreversibly specialized,
      precluding shifts between pathogenesis and mutualism.

PMID- 10884697
TI  - Early tetrapod evolution.

PMID- 10884698
TI  - Reply from M. Laurin, M. Girondot and A. de Ricqles.

PMID- 10884699
TI  - Sensitivity analysis, indirect interactions and inconsistency problems.

PMID- 10884700
TI  - Sensitivity analysis, indirect interactions and inconsistency problems.

PMID- 10884701
TI  - Reply from M. Mesterton-Gibbons.

PMID- 10884702
TI  - Symmetry, size and stress.

PMID- 10884704
TI  - Reply from T. Bjorksten, K. Fowler and A. Pomiankowski.

PMID- 10884703
TI  - Symmetry, size and stress.

PMID- 10884705
TI  - Tropical forests and atmospheric carbon dioxide.
AB  - Tropical forests play a major role in determining the current atmospheric
      concentration of CO2, as both sources of CO2 following deforestation and sinks of
      CO2 probably resulting from CO2 stimulation of forest photosynthesis. Recently,
      researchers have tried to quantify this role. The results suggest that both the
      carbon sources and sinks in tropical forests are significantly greater than
      previously thought.

PMID- 10884707
TI  - A worrying systematic decline.

PMID- 10884706
TI  - The nature of predation: prey dependent, ratio dependent or neither?
AB  - To describe a predator-prey relationship, it is necessary to specify the rate of
      prey consumption by an average predator. This functional response largely
      determines dynamic stability, responses to environmental influences and the
      nature of indirect effects in the food web containing the predator-prey pair.
      Nevertheless, measurements of functional responses in nature are quite rare.
      Recently, much work has been devoted to comparing two idealized forms of the
      functional response: prey dependent and ratio dependent. Although we agree that
      predator abundance often affects the consumption rate of individual predators,
      this phenomenon requires more attention. Disagreement remains over which of the
      two idealized responses serves as a better starting point in building models when
      data on predator dependence are absent.

PMID- 10884708
TI  - Modulation of immune function by dietary lectins in rheumatoid arthritis.
AB  - Despite the almost universal clinical observation that inflammation of the gut is
      frequently associated with inflammation of the joints and vice versa, the nature
      of this relationship remains elusive. In the present review, we provide evidence
      for how the interaction of dietary lectins with enterocytes and lymphocytes may
      facilitate the translocation of both dietary and gut-derived pathogenic antigens
      to peripheral tissues, which in turn causes persistent peripheral antigenic
      stimulation. In genetically susceptible individuals, this antigenic stimulation
      may ultimately result in the expression of overt rheumatoid arthritis (RA) via
      molecular mimicry, a process whereby foreign peptides, similar in structure to
      endogenous peptides, may cause antibodies or T-lymphocytes to cross-react with
      both foreign and endogenous peptides and thereby break immunological tolerance.
      By eliminating dietary elements, particularly lectins, which adversely influence
      both enterocyte and lymphocyte structure and function, it is proposed that the
      peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and
      thereby result in a diminution of disease symptoms in certain patients with RA.

PMID- 10884709
TI  - Essential fatty acids in the nutrition of severely neurologically disabled
      children.
AB  - Essential fatty acids (EFA) are important for the normal development and
      functioning of the brain, retina and immune competent cells. Severely
      neurologically handicapped children often have feeding difficulties, and the
      composition of the diet may be critical with respect to an optimal nutrient
      content. The aim of the present investigation was to evaluate if the dietary
      intakes and serum phospholipid concentrations of EFA were adequate in a group of
      severely neurologically impaired children in an institution. To achieve this, a
      prospective study was done. The investigation showed low dietary intakes of both
      n-6 fatty acids (FA) and n-3 FA. The serum concentrations of total n-6 FA,
      linoleic acid and 22:6n-3 (docosahexaenoic acid) as proportions of the total
      serum phospholipid FA concentration were initially low. The serum concentrations
      of 20:3n-9 and 22:5n-6 cholesterol, triacylglycerol, total saturated FA, total
      monounsaturated FA and apolipoproteins A-I and B were high compared with levels
      in a reference group of healthy children. Following supplementation with fish oil
      and soyabean oil, the serum lipid profile approached normal. We conclude that the
      study children had suboptimal intakes of EFA and that elevated serum
      concentrations of 20:3n-9 and 22:5n6 were useful serological markers of
      suboptimal EFA status. Recommended dietary allowances for EFA given as a
      percentage of energy underestimate EFA requirements in children with a low energy
      intake. Severely disabled children with feeding difficulties should probably be
      monitored with serum phospholipid FA measurements or calculation of dietary
      absolute intakes of EFA.

PMID- 10884710
TI  - Free and esterified fatty acid and cholesterol synthesis in adult males and its
      effect on the doubly-labelled water method.
AB  - The purpose of the present study was to estimate whole-body fatty acid and
      cholesterol synthesis in weight-stable adults and to determine the likely effect
      on the doubly-labelled water (DLW) method for measuring energy expenditure.
      Synthesis was measured by 2H incorporation over 14 d in six adult males in
      approximate energy balance following noradrenaline infusion to maximize
      mobilization of free fatty acid from adipose tissue. The inter-individual
      variation in synthesis rates was large and in one subject the proportion of free
      fatty acid synthesized was ten times that of the mean of the rest of the group;
      the fasting concentration of esterified fatty acid in this subject was five times
      that of the rest of the group indicating likely violation of the assumptions
      underlying the calculation of whole-body synthesis. After 14 d of labelling in
      the other five subjects, 0.9 (SEM 0.3)% of the circulating free fatty acid, 9.3
      (SEM 3.0)% of the esterified fatty acid, 14.6 (SEM 2.4)% of the free cholesterol
      and 28.3 (SEM 3.7)% of esterified cholesterol had been synthesized de novo. A
      high rate of synthesis correlated with a low pre-dose 2H abundance both within
      and between lipid classes suggesting that natural 2H abundance variations in some
      lipid classes may be used to determine their metabolic origin. Whole-body
      synthetic rates were 8 g/d for fatty acid and 0.3-0.5 g/d for cholesterol. These
      values correspond to very small errors on DLW-derived estimates of CO2
      production; -2.5 litres/d for fatty acid and -0.1 to -0.2 litres/d for
      cholesterol. These results, obtained in subjects typically consuming a diet with
      a lower fat and cholesterol content that the typical Western diet, suggest that
      the DLW method is unlikely to be affected by fatty acid and cholesterol synthesis
      in subjects in energy balance consuming a typical Western diet.

PMID- 10884711
TI  - Beneficial influence of an indigenous low-iron diet on serum indicators of iron
      status in patients with chronic liver disease.
AB  - The main Fe storage organ in the body is the liver. In patients with chronic
      liver disease, secondary Fe overload is common. Phlebotomy, often used in the
      West to reduce Fe overload to improve the efficacy of interferon therapy, is not
      socially acceptable in India. We assessed the efficacy of a low-Fe diet in
      reducing serum Fe levels. Nineteen patients with hepatitis B- and C-related
      chronic liver disease, ten with normal (< 25 mumol/l) baseline serum Fe levels
      (group A) and nine with high (> 25 mumol/l) serum Fe levels (group B) were
      included. All the subjects were advised to eat a low-Fe diet. The daily Fe intake
      was reduced approximately 50% by consumption of the rice-based diet. Haemoglobin,
      serum Fe, transferrin saturation index (TSI), ferritin and alanine transaminase
      (EC 2.6.1.2) levels were studied at 1 and 4 months. Dietary Fe intake and body
      weight were closely monitored. All patients complied with the dietary regimen and
      at 4 months significant (P < 0.001) reductions from baseline were seen in serum
      Fe (20 (SD 3) v. 12 (SD 4) mumol/l group A; 30 (SD 3) v. 19 (SD 7) mumol/l group
      B) and TSI (38 (SD 8) v. 23 (SD 9)% group A; 53 (SD 15) v. 34 (SD 13)%, group B)
      in both the groups, albeit earlier in group B subjects. Serum ferritin levels,
      however, reduced only in group A (112 (SD 62) v. 43 (SD 25) ng/ml, P < 0.05) and
      not in group B. Non-significant reductions in haemoglobin levels were seen in
      both groups. Alanine transaminase levels reduced significantly (P < 0.05) in both
      the groups (95 (SD 49) v. 44 (SD 25) IU/l, group A; 82 (SD 16) v. 51 (SD 14) IU/l
      group B). Thus, a low-Fe diet results in significant reductions in serum Fe and
      TSI levels, irrespective of baseline Fe levels. This diet should be evaluated to
      improve the efficacy of interferon therapy in patients with hepatitis B- and C
      related chronic liver disease.

PMID- 10884712
TI  - Intestinal trehalase activity in a UK population: establishing a normal range and
      the effect of disease.
AB  - Trehalose is a disaccharide, the main dietary source being mushrooms. It has been
      approved as an additive in the preparation of dried food. Isolated intestinal
      trehalase deficiency is found in 8% of Greenlanders, but is rare elsewhere. The
      normal range of trehalase activity and the incidence of isolated trehalase
      deficiency in the UK have not been reported. Patients (n 400) were investigated
      for suspected malabsorption. Endoscopic distal duodenal biopsies were taken for
      histological assessment and maltase, sucrase, lactase and trehalase estimation.
      Disaccharidase activities were determined by Dahlqvist's technique (Dahlqvist,
      1968). Most patients (n 369) had normal duodenal histology. In these, square root
      transformation of trehalase activity produced a normal distribution. The normal
      range (mean +/- 2 SD) was 4.79-37.12 U/g protein. One patient had an isolated
      borderline trehalase deficiency. The thirty-one patients with villous atrophy had
      significantly reduced disaccharidase activities. With ingestion of a gluten-free
      diet, maltase, sucrase and trehalase activities recovered to normal in most
      patients, whereas lactase activity did not. The normal range and very low
      incidence of isolated enzyme deficiency is comparable with that described in
      populations from the USA and mainland Europe. Activity is significantly reduced
      in untreated coeliac disease and recovers with treatment with a gluten-free diet.
      There is no place for routine determination of trehalase activity in the UK
      population and there should be no concern over the introduction of trehalose
      containing dried foods.

PMID- 10884713
TI  - In vitro fermentability of dextran, oligodextran and maltodextrin by human gut
      bacteria.
AB  - Anaerobic batch culture fermenters were used for a preliminary screening of the
      in vitro utilization by human gut microflora of dextran and novel oligodextrans
      (I, II and III) produced in the University of Reading (UK). Glucose and
      fructooligosaccharides (FOS) were used as reference carbohydrates. As expected,
      FOS acted as a good prebiotic in that it selectively increased numbers of
      bifidobacteria in the early stages of the fermentation. Dextran and oligodextrans
      each resulted in an enrichment of bifidobacteria in the batch cultures, with high
      levels of persistence up to 48 h. They also produced elevated levels of butyrate
      ranging from 5 to 14.85 mmol/l. To more effectively simulate conditions that
      prevail in different regions of the large intestine, a three-stage continuous
      culture cascade system was used to study further the fermentation of dextran, a
      low-molecular-mass oligodextran (IV) and maltodextrin. Oligodextran IV was shown
      to be the best substrate for bifidobacteria and lactobacilli with steady-state
      populations of bifidobacteria and lactobacilli being higher in all three vessels
      of the gut model than the respective populations resulting from dextran and
      maltodextrin. A maximum difference of 1.9 log was observed in vessel 1 for both
      bifidobacteria and lactobacilli in the case of dextran fermentation, with 1.4 log
      and 0.8 log in vessel 3 were the maximum differences for bifidobacteria and
      lactobacilli when maltodextrin was used as the carbohydrate source. Moreover,
      dextran and oligodextran appeared to stimulate butyrate production, with a
      maximum production up to 25.39 mmol/l in vessel 3 when fermenting dextran,
      followed by 21.70 mmol/l in the case of oligodextran IV and only 12.64 mmol/l in
      the case of maltodextrin.

PMID- 10884714
TI  - A cross-sectional study of dietary patterns with glucose intolerance and other
      features of the metabolic syndrome.
AB  - Previous epidemiological studies have demonstrated relationships between
      individual nutrients and glucose intolerance and type 2 diabetes, but the
      association with the overall pattern of dietary intake has not previously been
      described. In order to characterize this association, 802 subjects aged 40-65
      years were randomly selected from a population-based sampling frame and underwent
      a 75 g oral glucose-tolerance test. Principal component analysis was used to
      identify four dietary patterns explaining 31.7% of the dietary variation in the
      study cohort. These dietary patterns were associated with other lifestyle factors
      including socio-economic group, smoking, alcohol intake and physical activity.
      Component 1 was characterized by a healthy balanced diet with a frequent intake
      of raw and salad vegetables, fruits in both summer and winter, fish, pasta and
      rice and low intake of fried foods, sausages, fried fish, and potatoes. This
      component was negatively correlated with central obesity, fasting plasma glucose,
      120 min non-esterified fatty acid and triacylglycerol, and positively correlated
      with HDL-cholesterol. It therefore appears to be protective for the metabolic
      syndrome. Component 1 was negatively associated with the risk of having
      undiagnosed diabetes, and this association was independent of age, sex, smoking
      and obesity. The findings support the hypothesis that dietary patterns are
      associated with other lifestyle factors and with glucose intolerance and other
      features of the metabolic syndrome. The results provide further evidence for the
      recommendation of a healthy balanced diet as one of the main components of
      chronic disease prevention.

PMID- 10884715
TI  - Increased waist size and weight in relation to consumption of Areca catechu
      (betel-nut); a risk factor for increased glycaemia in Asians in east London.
AB  - Type 2 diabetes is commoner in Asians than Caucasians. Many nitrosamines are
      diabetogenic, causing both type 2 and type 1 diabetes. Of CD1 mice fed with betel
      nut or associated nitrosamines 8.5% develop glucose intolerance with marked
      obesity. Glycaemia and anthropometric risk markers for type 2 diabetes were
      therefore examined in relation to betel usage in 993 'healthy' Bangladeshis by
      one bilingual research-worker (N.M.). Of these, 12% had known diabetes. A further
      145 of 187 subjects 'at-risk' of diabetes (spot glucose > 6.5 mmol/l < 2 h after
      food, or > 4.5 mmol/l > 2 h after food) had a second blood glucose sample taken;
      sixty-one were confirmed as 'at-risk', and had an oral glucose tolerance test;
      nine new diabetics were identified. Multiple regression analysis showed that spot
      blood glucose values decreased with time after eating (P = 0.0005) and increased
      independently with waist size (P = 0.0005) and age (P = 0.0005) without
      relationships to other aspects of the diet, season or smoking. Waist size was
      strongly related to betel usage independent of other factors such as age. Betel
      use interacted with sex, relating to increasing glycaemia only in females. Since
      waist and age were the major markers of increasing glycaemia we suggest that
      betel chewing, a habit common to about 10% of the world population (more than 200
      million people) may contribute to the risk of developing type 2 diabetes
      mellitus.

PMID- 10884716
TI  - UK consumer perceptions of starchy foods.
AB  - To gain an understanding of UK consumer attitudes and beliefs regarding starchy
      foods and their dietary role, a questionnaire based on the theory of planned
      behaviour was developed and sent out to a UK consumer sample (n 800). The content
      focused on attitudes and beliefs towards starchy foods, perceived barriers
      towards increasing their intake (e.g. cost, habit, social influences),
      perceptions of personal and recommended starchy food intake, intention to
      increase starchy food intakes in the future and socio-demographic information.
      Responses (n 414) indicated that consumers have highly divergent attitudes and
      beliefs regarding starchy foods. These foods are seen as nutritious and good for
      one's health, but also as high in energy and not helping to control weight, and
      the overall intention to increase starchy food intake was extremely low. Possible
      barriers towards increasing starchy food intake were the perceptions that
      personal starchy food intakes were already high, beliefs that starchy food
      intakes should be reduced to achieve a healthier diet, and the view that personal
      starchy food intakes did not need to be changed any further, because (depending
      on attitude) individual's intakes had already been increased or reduced. The
      model including attitude and subjective norm had the best fit for predicting
      reported intention to increase starchy food consumption, with attitude being the
      strongest contributor. Addition of the factor 'family's liking of starchy foods'
      significantly improved the model. For reported starch intake, the model including
      attitude had the best fit, and addition of other factors did not improve the
      model. These findings indicate that health promotion strategies aimed at
      increasing complex carbohydrate intakes should take these perceptions into
      consideration; however, further work is required to examine how these potential
      barriers can best be addressed in practice.

PMID- 10884717
TI  - Estimation of population distributions of habitual nutrient intake based on a
      short-run weighed food diary.
AB  - There have been many attempts to characterize day-to-day variation in nutrient
      intake. This variation has a fixed component, associated with particular days of
      the week, and a random component. Both components were studied for a range of
      nutrients, using 4 d weighed diary data from a large, nationally representative
      survey of people aged 65 years or over. Since day-to-day variation may distort
      the characterization of the population distribution of habitual nutrient intakes,
      especially when diets are studied over only a small number of days, a statistical
      method was developed to correct for this distortion. Results suggested that
      population distributions of habitual nutrient intake could be accurately
      constructed from 4 d weighed diary data and that the method might be successfully
      applied to studies based on as little as 2 d of observation. The method is
      particularly valuable for correcting estimates of extreme nutrient intakes for
      biases induced by uneven representation of days of the week and by within-person
      variation.

PMID- 10884718
TI  - The flow of forage particles and solutes through segments of the digestive tracts
      of cattle.
AB  - An experiment was conducted to investigate the compartmental mean residence time,
      (CMRT) of feed residues in segments of gastrointestinal digesta of mature
      Holstein steers. The objective was to evaluate assumptions that feed residues
      flow through ruminal digesta as sequential mixing pools having age-dependent (GN)
      and age-independent (G1) distributed residence times respectively (GN-->G1 flow).
      The basal diet was a semi-tropical hay containing 98 g crude protein and 503 g
      apparently digestible DM per kg DM. The hay was consumed and feed residues of
      different size and/or previous digestion from the hay were inserted into the
      reticulo-rumen (rumen) and abomasum. Marker profiles appearing at the duodenum
      and faeces were fitted to various compartment models to estimate CMRT. Post
      abomasal CMRT did not differ among solutes or feed residues of different size and
      previous digestion and constituted only 5.8% of the CMRT for the entire
      gastrointestinal tract. Markers initially applied to orally or ruminally dosed
      feed residues exhibited profiles in duodenal digesta and faeces conforming to GN-
      >G1 flow. Previously undigested, masticated feed residues inserted into the
      dorsal rumen digesta had longer ruminal CMRT in the GN pool but not the G1 pool
      than did similarly inserted faecal small particles or normally ingested hay.
      These results support model assumptions of GN-->G1 flow within rumen digesta. The
      results support mechanisms proposed for the GN pool as the 'lag-rumination pool'
      and the G1 pool as the 'mass action turnover pool'. If further validated, rumen
      CMRT in cattle could be estimated from marker profiles in more easily obtained
      faeces to estimate ruminal CMRT required for feed evaluation systems.

PMID- 10884719
TI  - Influence of hepatic ammonia removal on ureagenesis, amino acid utilization and
      energy metabolism in the ovine liver.
AB  - The mass transfers of O2, glucose, NH3, urea and amino acids across the portal
      drained viscera (PDV) and the liver were quantified, by arterio-venous
      techniques, during the last 4 h of a 100 h infusion of 0 (basal), 150 or 400
      mumol NH4HCO3/min into the mesenteric vein of three sheep given 800 g grass
      pellets/d and arranged in a 3 x 3 Latin-square design. Urea irreversible loss
      rate (ILR) was also determined by continuous infusion of [14C]urea over the last
      52 h of each experimental period. PDV and liver movements of glucose, O2 and
      amino acids were unaltered by NH4HCO3 administration, although there was an
      increase in PDV absorption of non-essential amino acids (P = 0.037) and a trend
      for higher liver O2 consumption and portal appearance of total amino acid-N,
      glucogenic and non-essential amino acids at the highest level of infusion. PDV
      extraction of urea-N (P = 0.015) and liver removal of NH3 (P < 0.001), release of
      urea-N (P = 0.002) and urea ILR (P = 0.001) were all increased by NH4HCO3
      infusion. Hepatic urea-N release (y) and NH3 extraction (x) were linearly related
      (R2 0.89), with the slope of the regression not different from unity, both for
      estimations based on liver mass transfers (1.16; SE 0.144; P(b) not equal to 1 =
      0.31) and [14C]urea (0.97; SE 0.123; P(b) not equal to 1 = 0.84). The study
      indicates that a sustained 1.5 or 2.4-fold increase in the basal NH3 supply to
      the liver did not impair glucose or amino acid supply to non-splanchnic tissues;
      nor were additional N inputs to the ornithine cycle necessary to convert excess
      NH3 to urea. Half of the extra NH3 removed by the liver was, apparently, utilized
      by periportal glutamate dehydrogenase and aspartate aminotransferase for
      sequential glutamate and aspartate synthesis and converted to urea as the 2-amino
      moiety of aspartate.

PMID- 10884720
TI  - Ontogeny of the expression of leptin and its receptor in the murine fetus and
      placenta.
AB  - Leptin is a 167-amino acid protein that is secreted from adipose cells and
      expressed in placental tissues. It is important nutritionally in the regulation
      of energy balance, but also has other functions such as a role in reproduction.
      To investigate the function of the leptin system in fetal development we
      examined, primarily by in-situ hybridization and immunohistochemistry, the
      expression (both mRNA and protein) of leptin and its receptor (including the
      signalling splice variant) in tissues from 11.5, 13.5, 16.5 and 18.5 d postcoitus
      murine fetuses and associated placentas. We detected leptin mRNA (at low levels)
      and protein predominantly in the cytotrophoblasts of the labyrinth part of the
      placenta, an area of nutrient exchange between the developing fetus and the
      placenta, and in the trophoblast giant cells situated in the junctional zone at
      the maternal interface. In addition, leptin was strongly expressed in the fetal
      cartilage-bone and at a lower level in the hair follicles, heart, and liver of
      the murine fetus at differing stages of development. The leptin receptor,
      including the signalling splice variant, was also identified in specific fetal
      tissues. The physiological importance of expression of both leptin and the leptin
      receptor (OB-R and OB-Rb) in the placenta remains to be determined. In addition,
      the high levels of expression of leptin and its receptor in discrete areas of the
      murine fetus suggest that leptin has a critical role in fetal development.

PMID- 10884721
TI  - Relationship between the fatty acid composition of rat lymphocytes and immune
      functions.
AB  - The effects of dietary lipids on the fatty acid composition, activation and
      proliferation of lymphocytes were investigated. Weanling male Wistar rats were
      fed for 8 weeks on one of two low-fat diets which contained 50 g lipid/kg, or one
      of two high-fat diets containing 200 g lipid/kg, from either coconut oil or
      soyabean oil. The fatty acid composition of phospholipids from splenocyte
      membranes was affected by dietary lipid manipulation, and these differences
      influenced lymphocyte functions. Increased levels of linoleic acid in spleen
      lymphocytes correlated negatively with interleukin-2 receptor alpha-chain
      expression determined either by measuring the mean fluorescence or by the
      proportion of cells staining positive for CD25, and with the cell proliferation
      index. However, we found a positive correlation between interleukin-2 receptor
      alpha-chain expression determined by measuring the mean fluorescence and the cell
      proliferation index with the oleic acid concentration of spleen lymphocytes.
      Since phospholipid hydrolysis occurs early in lymphocyte activation,
      immunosuppressive effects induced by polyunsaturated fatty acids, described in
      the literature, could be due to an increase of linoleic acid or a decrease of
      oleic acid affecting many components of plasma-membrane-associated events
      involved in lymphocyte activation.

PMID- 10884722
TI  - Radiotherapy for benign diseases.

PMID- 10884723
TI  - Localization of breast lesions shown only on MRI--a review for the UK Study of
      MRI Screening for Breast Cancer. Advisory Group of MARIBS.
AB  - The UK study of screening for breast cancer compares mammography and dynamic
      contrast enhanced MRI of the breast in women at high genetic risk of developing
      cancer. Owing to the high sensitivity of MR in the breast, it is anticipated that
      some lesions will be visible only on MR. A key issue for the study is how to
      localize these lesions for histological verification and removal. This article
      reviews available methods and describes the current UK expertise and recent
      European developments. The use of MR compatible wires and markers has been
      explored in a phantom. The use of these markers in vivo is demonstrated in a case
      imaged by MR and mammography and further discussed. The susceptibility artefacts
      produced on MRI, and technical properties associated with these needles, wires
      and markers are discussed. The clinical pathway by which these lesions will be
      worked up for the study, and the quality control procedures for keeping the
      number of such biopsies to a minimum, are described. There is an urgent need for
      further centres in the UK to become proficient at removing lesions found only on
      MRI in support of this study and other breast MRI applications. The management of
      these lesions must be resolved in order to realize the full potential of MRI for
      screening for breast cancer in women at genetic risk, and for other diagnostic
      applications.

PMID- 10884724
TI  - HyCoSy--as good as claimed?
AB  - Hysterosalpingo contrast sonography (HyCoSy) has been compared favourably in the
      literature with hysterosalpingography (HSG). It does not require ionizing
      radiation and demonstrates the uterus and ovaries. HyCoSy is reported as being a
      safe, well tolerated, quick and easy investigation of Fallopian tube patency.
      Over a 1-year period HyCoSy was performed by two operators on 118 consecutive
      women who were thought likely to have patent Fallopian tubes. The examinations
      were graded using a local scale to assess discomfort and were correlated with
      tubal patency. HSG was performed on 116 patients by the same operators and
      discomfort recorded. 15 patients underwent both examinations. The degree of pain
      or reaction was graded 0 (no pain) to 4 (maximum) according to a locally devised
      scale. Costs of the two examinations were estimated. 89 patients examined by
      HyCoSy were graded 0-2. However, 23 had severe protracted pain and/or vasovagal
      reactions with bradycardia and hypotension. Of these, seven required
      resuscitation owing to prolonged symptoms, requiring treatment with atropine. 19
      of the 23 had bilaterally patent Fallopian tubes. Where subsequent HSG was
      performed, tubal occlusion was confirmed in 8 of 15 women. Other pathologies were
      noted in 29 of the HyCoSy patients and there were six technical failures. During
      the same period no severe adverse reactions occurred in 116 patients having HSG
      performed by the same operators. Three of the HSG examinations were technically
      unsuccessful. Discomfort following HyCoSy was much greater than that reported
      previously. Possible mechanisms are discussed but it does not appear to be
      related to tubal occlusion. Diagnostic accuracy, costs and discomfort compare
      unfavourably with HSG.

PMID- 10884725
TI  - Characteristics of small lung cancers invisible on conventional chest radiography
      and detected by population based screening using spiral CT.
AB  - Conventional chest radiography (CXR) is a poor diagnostic tool for detecting lung
      cancers at a surgically curable stage. To determine the visibility of peripheral
      small lung cancers on CXR, we retrospectively examined the usefulness of CXR
      using a consecutive series of 44 cases detected on CT screening and later
      confirmed by histopathology. All cases had been detected by low dose CT during a
      population based screening trial for lung cancer. The control group consisted of
      48 chest radiographs of normal subjects. Tumour diameters ranged from 6 mm to 45
      mm, with 95% (42/44) < or = 20 mm, and 5% (2/44) > 20 mm. CXR failed to detect
      77% (34/44) of all cancers, including 79% (33/42) < or = 20 mm and 50% (1/2) > 20
      mm. Of the 42 lung cancers < or = 20 mm, 74% (31/42) were located in the well
      penetrated lung zones and 71% (22/31) of these were missed on CXR. 26% (11/42)
      were concealed by hilar vessels, mediastinum, heart or diaphragm, and all (11/11)
      of these were missed on CXR. 93% (39/42) of the lung cancers < or = 20 mm were
      adenocarcinomas and 79% (31/39) of these were missed on CXR. 7% (3/42) were
      epidermoid carcinomas or small cell carcinomas and 66% (2/3) of these were missed
      on CXR. The overall accuracy of interpretation on CXR for lung cancers was 61%,
      sensitivity was 23% and specificity 96%. Although there was an association
      between presence of lung cancer and positive reading of CXR (chi 2 test of
      association, p < 0.05), the percentage of positive readings was only 23%. Thus,
      CXR was poor at visualizing CT detectable lung cancers of < or = 20 mm diameter,
      which are usually of very low density, and cannot be relied upon for detection of
      surgically curable small lung cancer.

PMID- 10884726
TI  - MRI of the claustrophobic patient: interventionally configured magnets.
AB  - The aim of this study was to determine whether or not claustrophobic patients
      would tolerate a scan in an open configuration interventional magnetic resonance
      (iMR) imaging unit, when they had failed to complete a diagnostic scan in a
      conventional MRI system. 50 claustrophobic subjects were entered into the study.
      Their response to the iMR environment was compared with their previous experience
      in an MRI scanner by means of a two-stage questionnaire. Part 1 was completed
      before their iMR scan and Part 2 following their attempt at imaging in the iMR
      unit. 60% (n = 30) of the participants were female and 40% (n = 20) were male,
      age range 25-71 years (mean 49.5 years). 48% (n = 24) were lumbar spine studies
      and 28% (n = 14) were studies of the head. 24% (n = 12) underwent scanning of
      other anatomical regions. 94% (n = 47) of participants underwent successful MRI
      in the interventional magnet without extra sedation. 6% (n = 3) failed to
      complete a diagnostic scan in the iMR machine. The GE Signa 0.5 T SP magnet
      allows successful MRI in 94% of the claustrophobic population who have failed to
      complete a scan in a conventional diagnostic machine.

PMID- 10884727
TI  - Upright dynamic MR defaecating proctography in an open configuration MR system.
AB  - We describe our experience evaluating an MR proctography technique using an open
      0.5 T MR system. Evacuation of a gadolinium-containing rectal contrast agent was
      dynamically imaged in the upright position using a fast gradient echo sequence.
      Anatomical and functional abnormalities were documented. Results from 40 patients
      who underwent this technique are reported. The method is proposed as an
      alternative to conventional fluoroscopic proctography.

PMID- 10884728
TI  - Computer assisted analysis of the chest radiograph lung area and prediction of
      failure of extubation from mechanical ventilation in preterm neonates.
AB  - Post-extubation chest radiographs (CXRs) are frequently requested on the neonatal
      intensive care unit, but it is controversial whether they generate useful
      information. A low lung volume assessed by measurement of functional residual
      capacity (FRC) post extubation has been demonstrated to predict extubation
      failure, which is a subsequent requirement for increased respiratory support. We
      have previously shown that the CXR lung area obtained by computer assisted
      analysis significantly correlated with FRC and, therefore, speculated that a low
      CXR lung area post extubation would reliably predict extubation failure. The aim
      of this study was to test the hypothesis by analysing CXRs from 20 infants, with
      median gestational age of 28 weeks (range 25-33 weeks) and postnatal age 4 days
      (range 1-11 days). CXRs were obtained within 4 h of extubation and were scanned
      and analysed using a Power Macintosh computer with a Wacom A5 Ultra pad and NIH
      image software. The cardiac, mediastinal and thymic shadows, and areas of
      perihilar and lobar consolidation were subtracted from the thoracic area to give
      the lung area. Seven infants failed extubation and differed significantly from
      the rest of the cohort only with regard to their CXR lung area, median
      gestational age, birth weight and postnatal age. Receiver operator characteristic
      (ROC) curves were constructed and the areas under each ROC curve were compared.
      Analysis demonstrated that a low CXR lung area and an older postnatal age were
      the best predictors of extubation failure. A post-extubation CXR lung area of <
      8.5 cm2 had the highest specificity (100%) in predicting extubation failure. We
      conclude that routine post-extubation CXRs can have a useful role.

PMID- 10884729
TI  - False positive thallium-201 SPECT imaging in brain abscess.
AB  - Three cases of intracranial 201Tl uptake, reported as positive tumour activity in
      patients with a final diagnosis of abscess, are described. 201Tl has been
      proposed as a useful oncotropic radiotracer in the diagnosis of brain tumour
      activity. These cases suggest a note of caution in the interpretation of 201Tl
      brain images in the differential diagnosis of an intracranial expanding mass.

PMID- 10884730
TI  - Quantitative ultrasound or clinical risk factors--which best identifies women at
      risk of osteoporosis?
AB  - Dual energy X-ray absorptiometry (DXA) is the current technique of choice to
      assess risk of future fracture and to diagnose osteoporosis as defined by bone
      mineral density (BMD). Guidelines for bone densitometry referral have been
      published listing clinical risk factors that might be considered grounds for
      assessment. However, these factors are known to be poorly predictive of
      subsequent BMD measurement and, accordingly, new inexpensive methods of selecting
      subjects for assessment should be sought. Quantitative ultrasound (QUS) of bone
      may be such a technique. Women (n = 250) considered by their general
      practitioners to be at risk of osteoporosis and who had been referred for DXA
      measurements of the spine and hip were recruited into the study. All underwent a
      QUS scan of the heel using a McCue CUBA Clinical machine, which measures
      broadband ultrasound attenuation (BUA) and velocity of sound (VOS), a clinical
      risk factor questionnaire, and spine and hip BMD measurement by a Norland XR-26
      bone densitometer. Patients were categorized according to published diagnostic
      criteria for BMD, and these were also applied to the QUS parameters. Risk factors
      were arbitrarily categorized into "low", "medium" and "high" risk groups. Kappa
      scores were calculated to analyse the agreement between different techniques.
      Receiver operator characteristic (ROC) analyses were undertaken to demonstrate
      the technique with the best sensitivity and specificity for the detection of low
      BMD at the spine and hip. Analysis of the bone mass data demonstrated only
      moderate agreement (kappa 0.33) between femoral neck and spine BMD with femoral
      neck BMD and BUA showing a very similar level of agreement (kappa 0.31). ROC
      analysis demonstrated that VOS followed by BUA was the best predictor of low BMD,
      with risk factors alone being significantly poorer; QUS parameters are better
      predictors than clinical risk factors for women with low BMD and could be used
      effectively at the primary care level to indicate those who should be considered
      for full osteoporosis assessment. However, further study into the cost
      effectiveness of this approach is required.

PMID- 10884731
TI  - Effective doses to patients from paediatric cardiac catheterization.
AB  - The Council Directive of the European Communities 97/43/Euratom requires dose
      assessment, especially for X-ray examinations of children and if high doses to
      the patient are involved. Both these aspects apply in cardiac catheterization and
      angiocardiography of children. Effective doses are a good indicator of radiation
      risk, particularly for leukaemia. Effective doses have been determined for 2114
      infants and children undergoing cardiac catheterization from 1984 to 1996 at the
      University Hospital in Essen. Conversion factors (effective dose/dose-area
      product) were calculated based on direct dose-area product measurements for
      posteroanterior (PA) and lateral (Lat) projections as well as on patient records
      and examination details. The factors are calculated for eight age groups of
      children, taking into account the X-ray tube voltage for fluoroscopy and cine
      film sequences, with and without zoom mode. Frequency distributions are presented
      for 2114 patients, for dose-area product, number of angiographic examinations
      (each combined with one cine-film sequence both PA and Lat) and for calculated
      effective doses. Highest effective doses are found in newborns (18.0 mSv and 6.5
      mSv 90th and 50th percentiles, respectively) compared with adolescents of 15-21
      years (8.0 mSv and 3.0 mSv 90th and 50th percentiles, respectively). Effective
      dose for cardiac catheterization is highest for newborns, in spite of lowest
      measured dose-area products, because the decreased value of the conversion
      factors overcompensates for the increase of dose-area product with age. This is
      especially important because of the higher tumour risk for equal effective dose
      for young children compared with adults.

PMID- 10884732
TI  - Factors affecting patient radiation exposure during routine coronary angiography
      in a tertiary referral centre.
AB  - Cardiac catheterization is carried out by an increasing number of operators from
      district hospitals as well as tertiary referral centres. Procedures are not
      standardized and are at the discretion of individual operators. The purpose of
      this study was to describe the pattern of patient radiation dose and screening
      times associated with diagnostic cardiac catheterization, and explore
      determinants of radiation dose to patients and staff. Data were collected from
      1337 diagnostic procedures carried out in two cardiac catheterization
      laboratories from January to June 1998. Screening time and radiation dose
      measured by dose-area product (DAP) meter were recorded. Status of the operator
      and type of investigation were determined. 22 operators had performed at least 15
      left ventriculograms with coronary angiography (total 944 procedures). The
      average (+/- SD) was 40 (+/- 22) per operator. Screening times for individual
      operators varied from 2.0 (+/- 1.3) min to 5.0 (+/- 4.3) min with no relationship
      between time and number of cases. Consultants and visiting physicians had longer
      screening times and greater patient DAP readings. In comparison with 115 cases of
      coronary angiography alone, left ventriculography increased DAP reading from
      14.24 (+/- 11.7) Gy cm2 to 20.26 (+/- 0.47) Gy cm2 (p < 0.0001). In 106 cases of
      coronary artery bypass graft angiography, an aortogram (n = 53) did not add
      significantly to radiation dose or screening time. A right heart catheter added
      approximately 5 min to screening time (9.13 (+/- 0.63) min with right heart (n =
      83) vs 3.96 (+/- 0.12) min without right heart (n = 1234)), but did not affect
      radiation dose significantly. There is a wide range of screening times and
      radiation doses related to diagnostic cardiac catheterization. Visiting and
      consultant staff use greater radiation doses. Left ventriculography adds
      significantly to patients' radiation exposure. Aortography does not add
      significantly to radiation dose in cases of graft angiography.

PMID- 10884733
TI  - Infants exposed to MRI in utero have a normal paediatric assessment at 9 months
      of age.
AB  - Any differences in detailed paediatric assessment at 9 months of age in infants
      exposed to echo planar MRI in utero from 20 weeks gestation to term were
      investigated by performing a case controlled prospective observational study of
      20 infants. They had all had serial echo planar MRI in the antenatal period and
      were compared with a control group born at the same time who had not. Statistical
      analysis employed likelihood ratios, odds ratios and 95% confidence intervals.
      The mothers of the control infants had a significantly higher standard of
      educational attainment (p = 0.005). A small but significant decrease in length (p
      = 0.047), and an increase in gross motor function (p = 0.023) of the fetuses
      exposed to echo planar imaging were demonstrated. No other significant
      developmental or social differences were seen between the two groups. Infants at
      9 months of age did not demonstrate any gross abnormality likely to be related to
      exposure to echo planar MRI in utero.

PMID- 10884734
TI  - Changed delivery of boron to tumours using electroporation for boron neutron
      capture therapy with BSH.
AB  - For effective boron neutron capture therapy (BNCT) it is important that a
      sufficient concentration of boron (10B) is present in the tumour during
      irradiation. This requirement represents a specific problem. The aim of this
      study was to test whether electroporation can be used as a non-specific drug
      delivery system to increase the delivery of sodium borocaptate-10B (BSH) into
      MCF7 (breast carcinoma) and B16F1 (melanoma) tumour cells in vitro and in B16F1
      tumours in vivo. For the in vitro determination of 10B uptake, the cells were
      incubated in medium containing BSH and exposed to electric pulses. Boron levels
      were determined by inductively coupled plasma atomic emission spectrometry. In
      vivo, tumours were exposed to electric pulses 3 min after intravenous BSH
      injection. At different times after exposure the 10B concentration was determined
      in tumours and in blood. A difference in the 10B accumulation in the two cell
      lines was observed after continuous incubation of cells with BSH. No accumulation
      of 10B was observed in MCF7 cells, whereas in B16F1 cells, 10B accumulated well
      and reached a plateau within 30 min. Electroporation of these cells resulted in
      an accumulation of 10B into MCF7 cells up to the level of 10B in B16F1 cells. In
      vivo, the application of electric pulses increased and prolonged the entrapment
      of 10B (BSH) in the B16F1 melanoma tumours. A sufficient concentration of 10B was
      present in the tumour exposed to electric pulses for up to 24 h. Boron was
      quickly washed out from the blood and the level was below the concentrations in
      the tumours exposed to electric pulses at 2 h. The results of this study show
      that electroporation may provide a tool to increase boron concentration in the
      cells that have impaired transport of BSH through the plasma membrane.
      Furthermore, prolonged entrapment of BSH in tumours in vivo may, in addition to
      electroporation, be caused by the modifying effect of electric pulses on blood
      flow.

PMID- 10884735
TI  - Calibration of pre-cut iridium-192 wires for low dose rate interstitial
      brachytherapy using a Farmer-type ionization chamber.
AB  - A technique, originally developed for calibrating small low activity caesium
      sources, which uses a Farmer-type ionization chamber, has been further developed
      for use with iridium wires. Correction factors have been generated to account for
      the finite source and detector sizes, and attenuation in the source carriers. The
      air kerma calibration factor for heavily filtered 280 kV X-rays was used for
      reference back to the National Standard. The results of this calibration method
      have been compared with the calibration figures given by the manufacturers over a
      5 year period for the emissions from 50 batches of wires of varying strengths.
      Agreement to within +/- 3.2% was achieved in all cases, establishing that the
      method is satisfactory for acceptance testing purposes. The mean agreement was
      good to within 0.2%, but the possibility of a systematic error of between 1% and
      3% existing both in this method and in the method used by the manufacturer is
      discussed.

PMID- 10884736
TI  - Intravenous extension of lung carcinoma to the left atrium: demonstration by
      positron emission tomography with CT correlation.
AB  - Intravenous extension of lung carcinoma is rare. A right upper lobe bronchogenic
      carcinoma with unusually elongated intravenous extension to the left atrium was
      first visualized with positron emission tomography (PET) and then confirmed with
      dynamic CT. The PET appearance of intravascular tumour spread is striking, and
      presents only a short differential diagnosis.

PMID- 10884737
TI  - Atypical presentation of pleural tuberculosis: CT findings.
AB  - Contrast enhanced CT examination of a 22-year-old male with pleuritic chest pain
      showed pleural-based nodular thickening and masses without any parenchymal
      involvement or mediastinal lymphadenopathy. Pathological examination following
      right parietal pleural decortication showed multiple granulomas with caseation
      necrosis typical of tuberculosis. Pleural tuberculosis presenting with multiple
      pleural nodules and masses without parenchymal involvement or lymphadenopathy
      has, to our knowledge, never been reported in the English literature.

PMID- 10884738
TI  - Acquired anomalous intrapulmonary venous connection secondary to pulmonary venous
      stenosis.
AB  - An unusual case of acquired development of anomalous intrapulmonary venous
      connection with pulmonary venous stenosis is presented. Appearances on a chest
      radiograph resembled the "scimitar" sign in a patient with previous surgery for
      partial anomalous pulmonary venous return. Spiral CT and pulmonary arteriography
      showed stenosis of the right upper pulmonary vein and an anomalous intrapulmonary
      venous connection between the right upper pulmonary vein and the right lower
      pulmonary vein. We consider the slow progression of pulmonary vein stenosis led
      to anomalous intrapulmonary venous connection as an intrapulmonary collateral.

PMID- 10884739
TI  - Retroperitoneal fibrosis: typical and atypical manifestations.
AB  - Retroperitoneal fibrosis (RPF) is a well described clinical entity that is being
      diagnosed with increasing frequency. RPF is characterized by replacement of the
      normal tissue of the retroperitoneum with fibrosis and/or chronic inflammation.
      However, aetiology, clinical presentation and radiological appearance in many
      cases are protean. Up to 15% of patients have additional fibrotic processes
      outside the retroperitoneum. In the abdomen, RPF may spread contiguously to
      involve multiple structures in both the retroperitoneum and the peritoneal cavity
      or multiple non-contiguous sites may be involved. We retrospectively reviewed 30
      patients (19 male, 11 female; age range 28-79 years) with biopsy proven RPF.
      Although we found RPF most commonly as an isolated fibrotic plaque in the lower
      lumbar region (18 patients), 12 patients (40%) presented with RPF in atypical
      locations (4 peripancreatic, 1 periduodenal, 7 pelvic). The RPF was non-malignant
      in 24 patients (21 idiopathic, 2 perianeurysmal, 1 ergot-derivative treatment)
      and malignant in six cases. We present a pictorial review of the varied
      appearances of RPF, concentrating on atypical sites. The radiological
      differential diagnosis and its appearance with various imaging modalities are
      discussed. Current concepts with respect to management, prognosis and treatment
      are summarized.

PMID- 10884740
TI  - Bilateral neck masses.

PMID- 10884741
TI  - Intensity modulated radiation therapy: a clinical review.
AB  - Intensity modulated radiotherapy represents a significant advance in conformal
      radiotherapy. In particular, it allows the delivery of dose distributions with
      concave isodose profiles such that radiosensitive normal tissue close to, or even
      within a concavity of, a tumour may be spared from radiation injury. This article
      reviews the clinical application of this technique to date, and discusses the
      practical issues of treatment planning and delivery from the clinician's
      perspective.

PMID- 10884742
TI  - Parametric mapping of scaled fitting error in dynamic susceptibility contrast
      enhanced MR perfusion imaging.
AB  - The purpose of this study was to examine the benefits of routine generation of a
      parametric image of scaled curve fitting errors in the analysis of dynamic
      susceptibility contrast enhanced MR perfusion imaging. We describe the scaled
      fitting error (SFE), which reflects the magnitude of potential errors in the
      estimation of perfusion parameters from dynamic susceptibility contrast enhanced
      studies. The SFE is the root-mean-square error between the observed values in the
      time course of change of effective transverse relaxation rate (delta R2* (t)) in
      tissue and the theoretical values derived by gamma variate curve fitting, scaled
      with a simple function related to the area under the fitted gamma variate curve.
      The SFE was tested using Monte Carlo simulation and by observations in normal
      volunteers and patients. This demonstrated that the SFE was linearly related to
      uncertainties in calculation of the values of relative cerebral blood volume
      (rCBV) and relative mean transit time (rMTT). High spatial resolution SFE maps
      were obtained in all volunteers and patients. In normal brain, SFE was
      consistently higher in white matter than in grey matter. In 54/85 patients with
      neurodegenerative or vascular brain disease, SFE maps showed focal areas with
      high values owing to poor signal to noise ratio in delta R2*(t). Increased SFE
      was also found in 11/54 brain tumours owing to loss of conformance of delta
      R2*(t) to the gamma variate function. SFE mapping is simple to implement and the
      computational overhead is negligible. It is concluded that parametric maps of SFE
      allow visual and quantitative comparison of fitting errors with the theoretical
      gamma variate model between anatomical regions and provide a quality control
      device to rapidly assess the reliability of the associated rCBV and rMTT
      estimations.

PMID- 10884743
TI  - The impact of FDG positron emission tomography imaging on the management of
      lymphomas.
AB  - The role of 2-(F-18)-fluoro-2-deoxy-D-glucose positron emission tomography (FDG
      PET) imaging in the management of patients with lymphoma has been evaluated. 29
      patients (12 Hodgkin's disease, 17 non-Hodgkin's lymphoma (NHL)) who underwent
      FDG-PET imaging during their lymphoma treatment programme were reviewed
      retrospectively. Correlation between FDG-PET and CT was evaluated, together with
      the impact upon clinical management of the findings on FDG-PET imaging. FDG-PET
      added extra information to the findings on clinical examination and CT in 12
      patients (41%). This was seen both in patients with negative and positive CT
      scan. Two false positive FDG-PET scans were seen, reflecting FDG uptake in
      extranodal sites. Information from FDG-PET imaging resulted in a change in
      clinical management in 10 patients (34%); in two, initial management was altered,
      and in eight consolidation therapy after completion of initial chemotherapy was
      influenced. These changes in clinical management occurred in six patients with
      high grade NHL, two with low grade NHL and two with Hodgkin's disease. No
      specific subgroup was identified in whom FDG-PET was particularly discriminant.

PMID- 10884744
TI  - Radionuclide bone imaging for detection of mandibular invasion by squamous cell
      carcinoma.
AB  - The assessment of mandibular invasion is an important part of the pre-operative
      staging of oropharyngeal squamous cell carcinoma. When bone is surgically
      resected, histology often shows no direct bone invasion, yet such resections are
      associated with post-operative complication and morbidity. This prospective study
      of a large group of patients aims to lay down criteria for bone invasion using
      radionuclide bone imaging and orthopantomography, and to test their effectiveness
      when compared with histological analysis. 77 patients with proven squamous cell
      carcinoma of the oral cavity were investigated pre-operatively by radionuclide
      bone imaging and orthopantomography. All had bone resected as part of complete
      resection of the tumour. One patient had systemic bone metastases and was,
      therefore, excluded. In the remaining 76 patients, there were four false positive
      assessments for bone invasion radiologically and no false negatives. There were
      48 true positive results and 24 true negatives, giving a sensitivity of 100% and
      specificity of 86%. It is concluded that correct application of the outlined
      criteria for bone invasion demonstrated that radionuclide bone imaging and
      orthopantomography are a sensitive test for bone invasion, with an acceptable
      level of specificity.

PMID- 10884745
TI  - The incidence and significance of testicular microlithiasis in a subfertile
      population.
AB  - The objective of this study was to assess the frequency of testicular
      microlithiasis (TM) in infertile men who underwent testicular ultrasound and to
      determine any causative or associated factors. The case notes of 159 consecutive
      patients who were referred for testicular ultrasound in the investigation of male
      factor infertility were reviewed. Microcalcification was found in 10 cases
      (6.2%). This was unilateral in all cases and six patients had clinical evidence
      of a varicocele. Five cases had minimal calcification and five had marked TM. On
      patient had a past history of testicular maldescent and another of testicular
      torsion. Sperm function (as assessed by sperm count, motility and the sperm
      migration test) was variable within the 10 patients and there was no correlation
      with hormone profiles or testicular size. There was a statistical difference
      between a number of investigations in those patients with minimal degrees of
      calcification and those with TM (sperm migration test (SMT), namely sperm
      migration and sperm motility (p < 0.05, Mann-Whitney U test)). The results showed
      a higher than expected incidence of TM. Patients with marked TM seemed to have
      poorer sperm function than those with minimal calcification. There was a high
      incidence of co-existing pathology, for instance scrotal varicocele and
      cryptorchidism, although the numbers in this study were small and further studies
      need to be carried out to determine the exact nature and significance of this
      condition.

PMID- 10884746
TI  - Effects of titanium prosthesis, offset and size of field of view on bone mineral
      density measurements using quantitative computed tomography.
AB  - To estimate the accuracy of quantitative computed tomography (QCT) as a method to
      measure bone mineral density (BMD) in the vicinity of a titanium prosthesis, we
      investigated the effects of (1) titanium prosthesis, (2) offset of the
      longitudinal axis of the bone to be examined from that of the gantry of the CT
      scanner, (3) size of the field of view (FOV) and (4) the combination of these
      effects on CT based measurements of mineral density of cortical and cancellous
      bone specimens. 14 bovine cortical bone parallelepipeds and 14 bovine cancellous
      bone parallelepipeds were used in this investigation. The bone specimens were
      scanned with and without a titanium prosthesis, when centered in the gantry of
      the CT scanner and offset from the axis of the gantry of the CT scanner at a
      distance of 14 cm. Image data were then reconstructed separately with a FOV of 10
      cm and 30 cm. All BMD values taken from CT images obtained under different
      scanning condition were compared with the BMD values of the corresponding bone
      parallelepiped obtained under standard condition (centered in the gantry of the
      CT scanner, 10 cm FOV, without titanium prosthesis). When centered in the gantry
      of the CT scanner, the mean relative difference of BMD measurements caused by the
      presence of the titanium prosthesis was less than 1% for both cortical bone and
      cancellous bone. Size of the FOV had a negligible effect on BMD measurements.
      Offset at 14 cm, however, caused a significant difference in BMD measurements (p
      < 0.001). It was concluded that titanium prosthesis did not interfere with BMD
      measurements of cortical and cancellous bone when both the specimen and
      prosthesis were centered in the gantry of the CT scanner. However, the effect on
      BMD measurements of offset at 14 cm combined with the presence of a titanium
      prosthesis in bone was significant.

PMID- 10884747
TI  - Correlation of patient skin doses in cardiac interventional radiology with dose
      area product.
AB  - The use of X-rays in cardiac interventional radiology has the potential to induce
      deterministic radiation effects on the patient's skin. Guidelines published by
      official organizations encourage the recording of information to evaluate this
      risk, and the use of reference values in terms of the dose-area product (DAP).
      Skin dose measurements were made with thermoluminescent dosemeters placed at
      eight different locations on the body. In addition, DAP was recorded in 100
      patients for four types of interventional radiology procedures. Mean, median and
      third quartile for these results are presented. Maximum skin dose values found
      were 412 mGy, 725 mGy, 760 mGy and 1800 mGy for coronary catheterization,
      coronary catheterization with left ventricle investigation, and percutaneous
      transluminal angiography without and with stenting, respectively. Median DAPs for
      these same procedures were, respectively, 5682 cGy cm2, 10,632 cGy cm2, 10,880
      cGy cm2 and 13,161 cGy cm2. The relationship between DAP and skin dose was
      investigated. We found a poor correlation of DAP with maximum skin dose (r =
      0.77) and skin dose indicator (r = 0.78). Using conversion factors derived from
      Monte Carlo simulations, skin dose distributions were calculated based on the
      measured DAPs. Agreement between the calculated skin dose distribution, using DAP
      values averaged over a group of patients who underwent coronary catheterization
      and left ventricle investigation, and the measured skin dose averaged over the
      same group of patients was very good. However, there were large differences
      between the calculated skin doses using the individual DAP data per patient and
      measured skin doses for individual patients (r = 0.66). Hence, calculation of
      individual skin doses based on the specific DAP data per patient is not reliable
      and therefore measuring skin dose is preferable.

PMID- 10884749
TI  - Dosimetric properties of the Theraview fluoroscopic electronic portal imaging
      device.
AB  - Electronic portal imaging devices (EPIDs) can be used for non-imaging
      applications in radiotherapy such as patient dosimetry. Of the systems available,
      the fluoroscopic camera-based EPID Theraview (InfiMed Inc.) has not been studied
      to date, and a review of the dosimetric properties of the system is presented
      here. In the "single set-up" mode of image acquisition, pixel intensity increases
      sublinearly with applied dose. The response was dependent on the system's video
      signal gain and showed a threshold dose to the detector in the range 0.05-0.35
      cGy, and pixel saturation at detector doses in the range 1.2-1.6 cGy. Repeated
      exposures of the EPID were observed to be extremely reproducible (standard
      deviation 0.5%). The sensitivity of the system showed a linear decline of 0.04%
      day-1 over a 68-day period, during which time the relative off-axis response
      within 10 x 10 cm2 field was constant to within a standard deviation of 0.56%.
      The system shows spatial non-uniformity, which requires correction for
      application to dose measurements in two-dimensions. Warm-up of the camera control
      unit required a period of at least 40 min and was associated with an enhancement
      in pixel intensity of up to 12%. A radiation dose history effect was observed at
      doses as low as 0.2 Gy. Camera dark current was shown to be negligible at normal
      accelerator operation. No discernible image distortion was found. Mechanical
      stability on gantry rotation was also assessed and image displacement of up to 5
      mm at the isocentre was observed. It was concluded that the device could be used
      for dosimetry provided necessary precautions were observed and corrections made.

PMID- 10884748
TI  - A pilot study to assess the feasibility of prior scalp cooling with palliative
      whole brain radiotherapy.
AB  - The objective of this work was to perform a feasibility study on the use of scalp
      cooling during palliative whole brain radiotherapy. Seven patients (1 male, 6
      female) with good performance status underwent scalp cooling prior to and during
      radiotherapy for cerebral metastases. Five patients were prescribed 12 Gy in two
      fractions and two patients were prescribed 20 Gy in five fractions. Phantom
      thermoluminescent dosemeter (TLD) studies to assess the build-up effect from the
      scalp cap were performed. Seven out of eight patients that were offered scalp
      cooling completed treatment uneventfully. One patient reported discomfort on
      application of the scalp cap and continued treatment without scalp cooling. No
      patients reported other adverse effects from use of the cap during treatment or
      at follow-up. TLD studies demonstrated a 55-80% increase in dose to the scalp
      after application of the scalp cap. All patients experienced hair loss. Scalp
      cooling caps are well tolerated through a course of palliative whole brain
      radiotherapy. The scalp dose is significantly increased owing to a bolus effect
      from the scalp cap.

PMID- 10884750
TI  - "Anode heel effect" on patient dose in lumbar spine radiography.
AB  - Appropriate use of the "anode heel effect" of the output beam from an X-ray tube
      can reduce the effective dose to patients in some common radiological
      examinations. We investigated the variation in radiation intensity across the X
      ray beam caused by the anode heel effect, and quantified the difference in
      absorbed dose to critical organs resulting from lumbar spine X-ray projections
      carried out with the two possible orientations of the patient along the tube axis
      (cathode to anode). A Rando phantom and some high sensitivity thermoluminescent
      dosemeters (TLDs) (LiF:Mg,Cu,P) were used. With the tube axis horizontal,
      radiation intensity profiles, parallel and perpendicular to the axis, were
      measured. Lumbar spine radiographs were recorded using the Rando phantom in the
      standard anteroposterior (AP) and lateral projections. TLD pellets were used to
      measure the absorbed radiation dose at various sites corresponding to critical
      organ tissues (ovaries, testes, breasts, thyroid and lens). Each set of
      projections was recorded in two phantom orientations, first with the phantom head
      placed towards the cathode end of the X-ray tube, and then in the reverse
      direction. From the radiation intensity profile of the incident X-ray beam, the
      "cathode end" to "anode end" air dose ratio was found to be 1.8. In lumbar spine
      radiography, with the phantom head placed towards the anode end of the X-ray
      tube, the ovaries and testes received an average dose 17% and 12% higher,
      respectively, in the lateral projection, and 16% and 27% higher, respectively, in
      the AP projection, than those obtained in the reverse "patient" orientation.
      These results indicate that patients (particularly females) should always be
      positioned with the head placed towards the cathode end of the X-ray tube for
      lumbar spine radiography to achieve significant dose reductions.

PMID- 10884751
TI  - A collision prevention software tool for complex three-dimensional isocentric set
      ups.
AB  - During treatment planning it can be difficult to check whether a particular plan
      is workable, that is it avoids obstructing treatment beams with parts of the
      patient couch and it avoids collisions between the treatment machine head and the
      patient couch. To overcome this problem, the trigonometric relationships between
      the placement of treatment beams and the patient couch are examined. From these
      relationships a set of useful equations that can be generally applied is derived.
      The application of these equations practically as a simple (non-graphical)
      planning tool is described. The resulting tool enables the feasibility of a plan
      to be checked during treatment planning, and gives guidance as to how a patient
      could be repositioned to allow the use of a plan when potential beam obstructions
      are detected, prior to verification of the treatment on a simulator.

PMID- 10884752
TI  - CT findings in post-operative subphrenic abscess with teratomatous inclusions.
AB  - A 39-year-old woman presented with abdominal pain after tubal sterilization. CT
      showed a subphrenic abscess with fatty inclusions owing to laceration or rupture
      of a mature ovarian teratoma. Although subphrenic abscess is a well recognized
      post-operative complication, and ovarian teratomas are frequent, a teratomatous
      inclusion within a subphrenic abscess is a unique finding.

PMID- 10884753
TI  - Acute radiation-induced hepatic injury: evaluation by triphasic contrast enhanced
      helical CT.
AB  - We report a case of radiation-induced hepatic injury as a complication of
      localized abdominal radiotherapy for epidural spread of non-Hodgkin's lymphoma.
      The liver was evaluated by triphasic contrast enhanced helical CT scan. Hepatic
      biopsy demonstrated changes typical of veno-occlusive disease. The pattern of
      hepatic enhancement resulting from the radiation-induced veno-occlusive process
      is discussed.

PMID- 10884754
TI  - Massive rise in thyroglobulin with adult respiratory distress syndrome after
      embolisation of thyroid cancer metastasis.
AB  - A patient with long-standing metastatic disease from a well differentiated
      papillary cell carcinoma of the thyroid underwent embolisation of a painful large
      sacral metastasis. Following embolisation she had a massive rise in circulating
      serum thyroglobulin (Tg) levels coinciding with the development of adult
      respiratory distress syndrome (ARDS) on the tenth day without any other obvious
      cause. The patient subsequently recovered. The time course suggests that ARDS in
      this case might have resulted from aggregation of Tg molecules in the pulmonary
      microcirculation.

PMID- 10884755
TI  - Conformal radiation therapy for hepatoma with portal vein thrombosis.
AB  - A 43-year-old male patient was diagnosed as having hepatocellular carcinoma with
      portal vein thrombosis and arterioportal shunts. Three-dimensional conformal
      radiation therapy (3DCRT) with high focal dose was given to the left portal
      venous area. Shrinkage of the tumour and thrombus, disappearance of the
      arterioportal shunts and restoration of the hepatopedal flow of the portal vein
      was noted 3 months after treatment. The patient received further transarterial
      embolisation and achieved successful tumour control. No serious complications
      were encountered. 3DCRT is technically feasible and effective to treat a small
      volume of liver tissue with a high dose of radiation in this advanced disease.

PMID- 10884756
TI  - Bilateral radical radiotherapy in a patient with uterus didelphys.
AB  - We report a case of congenital abnormality of uterus didelyphys in a patient who
      developed invasive carcinoma of the cervix. She received radical radiotherapy by
      a combination of external beam pelvic radiotherapy and high dose rate
      brachytherapy by insertion of afterloading catheters into both uterine canals. A
      newly defined prescription point was used midway between the two catheters and 2
      cm above the mean cervical os position. The classical point A was regarded as
      inappropriate in this patient with a rare condition. Acute toxicity was minor and
      the patient is tumour free with no significant normal tissue late effects after
      follow-up of nearly 3 years.

PMID- 10884757
TI  - Acute appendicitis with intestinal non-rotation presenting with partial small
      bowel obstruction diagnosed on CT.
AB  - The findings of acute appendicitis on CT have been extensively described in the
      literature. This is a report of a case of acute appendicitis in a patient with
      intestinal non-rotation presenting with partial small bowel obstruction. Analysis
      of the CT findings allowed a correct diagnosis.

PMID- 10884758
TI  - The radiological approach to precocious puberty.
AB  - Precocious puberty is caused by a heterogeneous group of disorders, which range
      from idiopathic to malignant tumours. The radiologist's role is to help: (1)
      differentiate precocious puberty from pubertal variants; (2) identify the
      underlying cause of precocity if present; and (3) assess for effectiveness of
      treatment. This pictorial review discusses the types of precocious puberty and
      their underlying aetiologies, differentiates precocious puberty from pubertal
      variants and illustrates the appropriate imaging evaluation for the patient
      diagnosed with precocious puberty.

PMID- 10884759
TI  - Awareness by radiology staff of the difference in radiation risk from two
      opposing lateral lumbar spine examinations.

PMID- 10884760
TI  - A case of isolated third nerve palsy with pupil involvement.

PMID- 10884761
TI  - The National Health Service needs a voice of its own.

PMID- 10884762
TI  - Multiple sclerosis: care needs for 2000 and beyond.

PMID- 10884763
TI  - Emergency management of meningitis.

PMID- 10884764
TI  - Cerebral venous thrombosis: pathogenesis, presentation and prognosis.

PMID- 10884765
TI  - Cerebral venous thrombosis: making the most of imaging.

PMID- 10884766
TI  - Cerebral venous thrombosis: medical therapy.

PMID- 10884767
TI  - Cerebral venous thrombosis: local thrombolysis.

PMID- 10884768
TI  - Knowledge for the clinician. 2. Reference material: books and multimedia
      packages.

PMID- 10884769
TI  - Consultation skills of medical students before and after changes in curriculum.
AB  - The University of Manchester Medical School has adopted problem-based learning as
      its main educational method, with a change of emphasis from a biomedical to a
      biopsychosocial approach. The training of junior medical students in clinical
      interviewing is intended to reinforce and develop their interpersonal skills. We
      measured the impact of this new curriculum by assessing two intakes of students
      covering the period before and after its introduction; a third intake was later
      added to examine the effect of further curriculum adjustments. 86 students,
      randomly selected, were videorecorded conducting diagnostic interviews with
      standardized patients 10 weeks after they had started to learn clinical
      interviewing. Two instruments were developed--a 23-item communication skills
      scale and a 13-item information-gathering scale and both showed acceptable inter
      rater and test-retest reliability. Communication skills did not differ between
      years. The total score for information-gathering fell by 13% (95% confidence
      interval -20 to -6%, P < 0.001) in the first year after introduction of the new
      educational approach but returned to baseline the following year after further
      modification of the course. Although the new approach yielded no measurable
      improvement in the process of communication, assessment 10 weeks after the start
      of interview training may be too early to permit definitive conclusions. We
      conclude that it is possible to change to a more patient-centred emphasis in
      teaching medical interviewing. Some initial loss of information content was
      rectified by adjustment of the course. Our unfavourable early experience
      highlights the need to evaluate educational change.

PMID- 10884770
TI  - Slimming on the Internet.
AB  - The first 50 websites identified on searching the Internet for 'weight loss
      diets' were assessed systematically and their content compared with published
      clinical guidelines for management of obesity. The relevance and quality of the
      sites varied enormously. Only 3 confined themselves to sound dietary advice. Most
      promoted dietary supplements or other 'slimming aids', often of uncertain
      composition and based on dubious physiological principles. Potential hazards--for
      example, those of very low calorie diets--were rarely highlighted and certain
      regimens on offer were potentially dangerous.

PMID- 10884771
TI  - Adverse effects of spinal manipulation.
AB  - Guidelines on acute back pain recommend spinal manipulation, but some
      commentators express concern that the adverse effects are under-reported. Eleven
      chiropractors distributed questionnaires to 108 consecutive new patients aged >
      18 years, enquiring about adverse effects one hour, one day and two days after
      spinal manipulation. The forms were to be completed anonymously. 80
      questionnaires (74%) were returned, 68 suitable for analysis. 28 patients
      reported adverse effects at one hour after treatment, the most common of which
      were extra pain (14) and radiating pain (9). 8 had reactions beginning the
      morning after. No serious adverse effects were reported. The adverse reactions,
      recorded in 53% of respondents, are those to be expected from a treatment that
      entails initial discomfort. They need to be set against the long-term benefits of
      spinal manipulation.

PMID- 10884772
TI  - Bilateral gluteal compartment syndrome after 'ecstasy' hyperpyrexia.

PMID- 10884773
TI  - Restorative proctocolectomy for collagenous colitis.

PMID- 10884774
TI  - Groin sepsis after hip replacement: look beyond the hip.

PMID- 10884775
TI  - Migraine experiences as artistic inspiration in a contemporary artist.

PMID- 10884776
TI  - The first successful haemodialysis.

PMID- 10884777
TI  - Surgical correction of refractive error.

PMID- 10884778
TI  - Surgical correction of refractive error.

PMID- 10884779
TI  - Surgical correction of refractive error.

PMID- 10884780
TI  - The sin of Onan.

PMID- 10884781
TI  - The sin of Onan.

PMID- 10884782
TI  - The sin of Onan

PMID- 10884783
TI  - Modified approach to tailgut cyst excision.

PMID- 10884784
TI  - 'Grand mal' in hypotension.

PMID- 10884785
TI  - So you want to write a textbook?

PMID- 10884786
TI  - So you want to write a textbook?

PMID- 10884787
TI  - So you want to write a textbook?

PMID- 10884788
TI  - So you want to write a textbook?

PMID- 10884789
TI  - Antithrombotic therapy in atrial fibrillation.

PMID- 10884790
TI  - Antithrombotic therapy in atrial fibrillation.

PMID- 10884791
TI  - Differential diagnosis of varicose veins.

PMID- 10884792
TI  - The two cultures of medicine.

PMID- 10884793
TI  - Tyger tyger.

PMID- 10884794
TI  - Enhancing the financial performance of a health system laboratory network using
      an information system.
AB  - We describe the improvements created by successful implementation of a laboratory
      information system for a multi-institutional integrated delivery system,
      including an analysis of the financial results. Conditions at the outset of the
      project, methods of management and project design, selected aspects of services
      redesign and consolidation, integration of services among the sites and their
      effects on laboratory staff and productivity are illustrated. A method for and
      example of measuring the financial outcomes in the sense of quantifiable
      improvements in operating expenses and new revenue for a whole health system
      clinical laboratory computer system are discussed. In this health system, the
      measurable financial improvements facilitated by an information system were the
      ability to control operating expenses and to grow the hospital laboratory network
      through the development of an outreach program. With organizational commitment to
      process innovation and improvement, using team processes and customer-driven
      decision-making criteria, the financial performance of our consolidated
      laboratory network was enhanced substantially. A fully implemented laboratory
      information system is considered the major enabler of positive change when
      combined with a genuine commitment from all levels of staff and leadership. Over
      time, this system's financial return is several times that of the information
      system investment.

PMID- 10884795
TI  - The accuracy of combined cytopathologic and flow cytometric analysis of fine
      needle aspirates of lymph nodes.
AB  - We studied flow cytometry in 156 fine-needle aspirations (FNAs) of lymph nodes
      performed between June 1993 and September 1998. Information from flow cytometry
      was combined with cytomorphologic evaluation, and the diagnosis determined by
      using combined modalities was compared with tissue biopsy results or clinical
      follow-up. In 74 cases, a combined cytopathologic-flow cytometric diagnosis of
      lymphoma was made; histologic material was available for 52 patients; in no case
      was a benign process found. The lymphoma grade assigned agreed with
      histopathologic findings in 45 of 48 cases with a specific cytologic diagnosis.
      Treatment was initiated on the basis of the FNA alone for 17 of 52 patients with
      a history of lymphoma and in 22 additional patients with no follow-up biopsy.
      Among 71 cases in which the diagnosis using both modalities was benign, the only
      false-negative was 1 case of Hodgkin disease. Of the 156 cases, 11 were
      considered atypical or suggestive of lymphoma; biopsies from 8 of 10 patients
      revealed lymphoma. A combination of flow cytometry and cytomorphology of cells
      obtained by FNA of lymph nodes can distinguish between benign and malignant
      lymphoid infiltrates and support a diagnosis of lymphoma that permits definitive
      therapy in most cases.

PMID- 10884796
TI  - Characterization of CD13 and CD33 surface antigen-negative acute myeloid
      leukemia.
AB  - From a cohort of 220 adults with newly diagnosed acute myeloid leukemia (AML), 8
      (3.6%) exhibited a rare variant of aberrant membrane phenotype. It was
      characterized with typical myeloid morphologic and cytochemical patterns and
      absence of myeloid associated antigens (CD13, CD33, CD14, glycophorin A, CD61).
      According to the French-American-British criteria, disease in 5 patients was
      classified as M1 and in 3 patients as M2. CD34, CD38, HLA-DR, and CD45 were
      strongly expressed in 4 of 5, 3 of 3, 8 of 8, and 3 of 3 analyzed cases,
      respectively. CD7 antigen was strongly expressed in 4 of 6 patients. Except for
      predominance of male sex and high frequency of CD7 antigen expression, no other
      remarkable clinical or biologic characteristics were noted. Detected variant of
      AML with the unusual membrane phenotype (CD34+, HLA-DR-positive, CD38+, CD45+,
      CD7+) might represent an example of extreme asynchrony in sequences of
      morphologic and immunologic maturation or abnormal epitope expression on leukemic
      cell membrane molecules CD13 and CD33. Although the clinical significance of this
      AML variant is unclear, the existence of such cases demonstrates the continued
      need for simultaneous cytochemical and immunologic studies in the evaluation of
      acute leukemias.

PMID- 10884797
TI  - Marked increase in L-selectin-negative T cells in neonatal pertussis. The
      lymphocytosis explained?
AB  - The detailed immunophenotype of peripheral blood lymphocytes from a neonate with
      pertussis was determined by flow cytometry and compared with results from cord
      blood from healthy newborns. Most (72%) of the lymphocytes were CD3+ T cells with
      a normal CD4/CD8 ratio (2.5). The T cells were largely HLA-DR negative and
      CD45RA+, consistent with unstimulated naive T cells. Almost all of the CD4+ T
      cells were Leu8 (L-selectin, CD62L) negative, while almost all of the CD8+ T
      cells were CD28+. There was no increase in CD7- CD4+ T cells (Th2-like). No
      relative increase in CD16/56+ NK cells (5%) or CD19/20+ B cells was seen. The
      most dramatic finding in this case was the remarkable lack of expression of L
      selectin by the T cells. L-selectin expression is associated with homing of
      peripheral blood lymphocytes to lymph nodes. The dramatic reduction in L-selectin
      expression of the T lymphocytes in pertussis, perhaps induced by pertussis toxin,
      likely prevents homing of the T cells to peripheral lymphoid tissues and provides
      a likely explanation for the marked lymphocytosis noted in this disease.

PMID- 10884798
TI  - B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma involving bone
      marrow with an interfollicular pattern.
AB  - B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) may
      involve the bone marrow in nodular, interstitial, diffuse, or mixed patterns.
      However, B-cell CLL/SLL associated with large reactive germinal centers (the so
      called interfollicular pattern) involving the bone marrow is not reported. We
      describe 2 examples of B-cell CLL/SLL that subtotally replaced the bone marrow
      with an interfollicular pattern. In both cases, the neoplasms were composed of
      small round lymphoid cells; proliferation centers also were present. The
      neoplasms surrounded large reactive germinal centers that were devoid of
      peripheral mantle zones. The germinal centers were paratrabecular and
      nonparatrabecular in case 1 and nonparatrabecular in case 2. Flow cytometry
      immunophenotypic studies done on bone marrow aspiration samples of both cases
      showed a uniform population of neoplastic cells positive for pan-B-cell antigens
      and the CD5 and CD23 antigens. Immunohistochemical studies done on bone marrow
      biopsy sections supported the flow cytometry results and demonstrated that the
      germinal centers were negative for BCL-2. B-cell CLL/SLL may rarely involve the
      bone marrow with an interfollicular pattern. Knowledge of this pattern will
      prevent confusion with follicle center lymphoma and large cell transformation,
      both of which initially were considered in the differential diagnosis of these
      cases.

PMID- 10884799
TI  - A rapid and accurate closed-tube immunoassay for platelets on an automated
      hematology analyzer.
AB  - Accurate and precise platelet counts are important for patients with severe
      thrombocytopenia or who are receiving chemotherapy. We developed a novel flow
      cytometric analysis of platelets that may be particularly valuable for assessing
      the necessity for platelet transfusions. This ImmunoPlt (CD61) assay is based in
      part on CD61 monoclonal antibody labeling and has been automated and implemented
      on the CELL-DYN 4000 hematology analyzer. It is well suited for thrombocytopenic
      specimens, since it reduces interference by nonplatelet particles. It takes less
      than 5 minutes from closed-tube aspiration to report. Data for more than 350
      thrombocytopenic specimens demonstrate that the ImmunoPlt (CD61) assay is more
      accurate than the optical scatter or the impedance count for specimens with
      platelet counts between 1 and 60 x 10(3)/microL (1 and 60 x 10(9)/L). The
      ImmunoPlt (CD61) assay is more precise than the optical scatter or the impedance
      count for specimens with platelet counts between 1 and 50 x 10(3)/microL (1 and
      50 x 10(9)/L).

PMID- 10884801
TI  - Benign hematogone-rich lymphoid proliferations can be distinguished from B
      lineage acute lymphoblastic leukemia by integration of morphology,
      immunophenotype, adhesion molecule expression, and architectural features.
AB  - Distinction of normal B-lymphoid proliferations including precursors known as
      hematogones from acute lymphoblastic leukemia (ALL) is critical for disease
      management. We present a multiparameter assessment of 27 bone marrow samples
      containing at least 25% hematogones (range, 25%-72%) by morphologic review. We
      used flow cytometry to evaluate B-cell differentiation antigen and adhesion
      molecule expression and immunohistochemistry on clot sections to evaluate
      architectural distribution. Flow cytometry revealed that intermediately
      differentiated cells (CD19+, CD10+) predominated, followed in frequency by CD20+,
      surface immunoglobulin-positive cells, with CD34+, terminal deoxynucleotidyl
      transferase (TdT)-positive cells as the smallest subset. Adhesion molecules
      (CD44, CD54) were expressed more heterogeneously compared with expression in
      acute lymphoblastic leukemia. Immunohistochemistry revealed that CD34+, TdT
      positive cells were dispersed without significant clustering, while CD20+ cells
      exceeded CD34/TdT-positive cells in 24 of 25 cases. This multidisciplinary study
      demonstrates that hematogone-rich lymphoid proliferations exhibit a spectrum of B
      lymphoid differentiation antigen expression with predominance of intermediate and
      mature B-lineage cells, heterogeneity of adhesion molecule expression, and
      nonclustered bone marrow architectural distribution.

PMID- 10884800
TI  - Effects of chemotherapy (busulfan-hydroxyurea) and interferon-alfa on bone marrow
      morphologic features in chronic myelogenous leukemia. Histochemical and
      morphometric study on sequential trephine biopsy specimens with special emphasis
      on dynamic features.
AB  - We performed a retrospective clinicopathologic study on sequential biopsy
      specimens from 90 patients with Philadelphia chromosome-positive chronic
      myelogenous leukemia to study therapy-specific effects of busulfan (28 patients),
      hydroxyurea (32 patients), and interferon-alfa (IFN-alfa; 30 patients). Bone
      marrow specimens were evaluated by morphometry after silver impregnation and
      staining with monoclonal antibodies to identify reticulin fibers, nucleated
      erythroid precursors, megakaryocytes, and macrophages. To compute dynamics of
      histopathology implicating corresponding changes in time, relevant indices were
      calculated. Quantification of megakaryocytopoiesis and its precursor cell
      population showed a significant increase in the IFN-alfa and busulfan groups
      compared with the hydroxyurea group. These changes were associated with a
      development of myelofibrosis during therapy. Although a significant increase in
      fiber density was detectable in the busulfan group, the progression index proved
      to be twice as high after IFN-alfa therapy. In contrast, a considerable number of
      patients displayed a regression of myelofibrosis after hydroxyurea treatment. The
      general association of the megakaryocyte lineage with myelofibrosis was in line
      with experimental findings. The mature macrophage population and its activated
      subfraction revealed a marked proliferation (IFN-alfa group) during treatment.
      Growth and activation of macrophages may be compatible with their putative
      function during erythrocytopoietic regeneration and with stimulation of their
      phagocytic properties.

PMID- 10884802
TI  - Effect of clinical history on diagnostic accuracy in the cytologic interpretation
      of bronchial brush specimens.
AB  - There has been little study of the effect of clinical history on pathologic
      diagnostic accuracy. Five pathologists retrospectively examined 97 bronchial
      brush specimens with and without clinical historic information. Forty-nine
      patients had a biopsy-proven malignant lesion, and 48 had a benign lesion.
      Diagnostic accuracy with and without history for each pathologist was determined
      with likelihood ratios and receiver operating characteristic curves. The overall
      diagnostic accuracy with and without history was 0.84 and 0.76, respectively. The
      average negative predictive value of a benign diagnosis decreased from 89.2%
      (with history) to 74.0% (without history). Overall, the cytopathologists were
      more reluctant to make a definitive malignant diagnosis without history compared
      with history. The average positive predictive value of a malignant diagnosis with
      and without history was almost identical. The absence of history leads to lower
      diagnostic accuracy in the cytologic interpretation of bronchial brush specimens
      partly because pathologists underdiagnose malignant lesions.

PMID- 10884803
TI  - Apoptotic activity and bcl-2 immunoreactivity in meningiomas. Association with
      grade and outcome.
AB  - We retrospectively evaluated 90 meningiomas for bcl-2 expression, apoptosis
      counts (per 10 high-power fields [HPF]), MIB-1 labeling indices (LI), and mitosis
      counts (per 10 HPF). Characteristics were as follows: 37 low-grade (benign)
      meningiomas: mean apoptosis count, 1.2; MIB-1 LI, 1.0; mitosis count, 0.1; and
      bcl-2 positivity, 40%; 29 atypical meningiomas: apoptosis count, 3.3; MIB-1 LI,
      5.5; mitosis count, 2.2; and bcl-2 positivity, 62%; 24 malignant meningiomas:
      apoptosis count, 6.5; MIB-1 LI, 12.0; mitosis count, 6.0; and bcl-2 positivity,
      67%. By univariate analysis, MIB-1 LI, apoptosis and mitosis counts, and tumor
      grade were associated significantly with death due to tumor; by multivariate
      analysis, only mitosis count was independently associated with death due to
      tumor. We compared similar data for 27 patients with nonrecurrent tumors and 32
      patients with recurrent meningiomas. Histologic sections from the initially
      resected tumor and from the most recent recurrence were reviewed. Only the
      apoptosis count was significantly higher by univariate analysis in the initial
      resection specimens from tumors that ultimately recurred vs nonrecurrent tumors.
      Expression of bcl-2, MIB-1 LI, and mitosis count did not correlate with
      recurrence. By multivariate analysis, only extent of surgical resection was
      associated significantly with tumor recurrence. Although bcl-2 immunostaining was
      not associated statistically with outcome, bcl-2 positivity was more common in
      atypical and malignant meningiomas than in low-grade tumors.

PMID- 10884804
TI  - Distinct allelic loss patterns in papillary serous carcinoma of the peritoneum.
AB  - Tumor and normal tissues from 55 patients with papillary serous carcinoma of the
      peritoneum (PSCP) were analyzed. Polymerase chain reaction amplification of
      tandem repeat polymorphism was used to screen for loss of heterozygosity (LOH).
      We mapped 22 oligonucleotide primers to chromosomes 1p, 3p, 6q, 7q, 9p, 11p, 17p,
      17q, and Xq. Germline BRCA1 mutation status of 43 patients was determined
      previously. High frequencies (> 30%) of LOH in PSCP were observed on 6q, 9p, 17p,
      17q, and Xq. Compared with allelic loss of serous epithelial ovarian carcinoma
      (SEOC), the frequency of LOH was significantly lower in PSCP on 1p, 7q, 11p, 17p,
      and 17q. Of 43 cases screened for germline BRCA1 mutations, 9 cases were
      identified with mutations. The frequencies of LOH were not significantly
      different among the BRCA1-related and BRCA1-unrelated PSCP cases. The high LOH
      rate identified on 6q, 9p, 17p, 17q, and Xq in PSCP suggests that candidate tumor
      suppressor genes residing in these regions may be important for the development
      of the tumor. Compared with allelic loss of SEOC, PSCP exhibits a significantly
      lower frequency of LOH on chromosomes 1p36, 7q31.3, 11p15.1, 17p13.1, and 17q21.
      An increase in susceptibility to the acquisition of allelic loss in BRCA1-related
      PSCP cannot be identified.

PMID- 10884805
TI  - Neuroendocrine carcinomas (carcinoid tumor) of the thymus. A clinicopathologic
      analysis of 80 cases.
AB  - We studied 80 cases of primary thymic neuroendocrine carcinomas. Most patients
      had symptoms; approximately one third were asymptomatic. All cases were treated
      by surgical excision. The tumors were divided according to histopathologic
      features into low- (n = 29), intermediate- (n = 36), and high-grade (n = 15)
      types. The tumors displayed a variegated histologic appearance and unusual
      cytologic features. Some cases showed transition from low to high grade within
      the same tumor mass. Mitotic activity ranged from fewer than 3 to more than 10
      mitotic figures per 10 high-power fields, and most tumors displayed marked
      cellular atypia and areas of necrosis. In 73 patients, the tumor was confined to
      the anterior mediastinum. Positive immunohistochemical reaction was observed
      using antibodies for CAM 5.2 low-molecular-weight cytokeratins, broad-spectrum
      keratin, chromogranin, synaptophysin, and Leu-7. The clinical follow-up obtained
      in 50 patients correlated well with tumor differentiation. Therefore, the
      behavior of these tumors seems to correlate with histologic grade, which seems
      directly proportional to degree of differentiation. We propose replacing the term
      thymic carcinoid with thymic neuroendocrine carcinoma, which better reflects the
      aggressive biologic behavior of these tumors in the mediastinal location.

PMID- 10884806
TI  - Ovarian metastases from colorectal carcinoma. Clinicopathologic profile,
      immunophenotype, and karyotype analysis.
AB  - Ovarian metastases from colorectal carcinoma frequently mimic primary ovarian
      carcinomas. The present study was performed to identify possible criteria helpful
      in differential diagnosis. Twenty-three ovarian metastases from colorectal
      carcinomas and 23 primary ovarian carcinomas were evaluated clinicopathologically
      and immunostained with antigastric M1 antigen, cathepsin E, CA125, vimentin,
      estrogen and progesterone receptors, cytokeratins 7 and 20, and alpha-inhibin
      antibodies. We performed a conventional and molecular cytogenetic study on 5
      ovarian metastases from colorectal carcinoma using direct preparation, Q banding
      techniques, and fluorescence in situ hybridization. Integration of
      clinicopathologic, immunohistochemical, and cytogenetic features is helpful for
      the differential diagnosis of metastases of colorectal carcinomas from primary
      ovarian carcinomas. Bilaterality, extrapelvic spreading, high mitotic index, and
      cytokeratin 20 immunoreactivity, and lack of M1, CA125, and cytokeratin 7
      immunoreactivity favor the diagnosis of ovarian metastases from colon carcinomas.
      The identification of 13q gain as a peculiar, sensitive, and specific marker of
      colorectal carcinomas seems relevant.

PMID- 10884807
TI  - What are the CD34+ cells in benign peripheral nerve sheath tumors? Double
      immunostaining study of CD34 and S-100 protein.
AB  - To determine whether CD34 expression in nerve sheath lesions was found in a
      unique cell population or in a subset of nerve sheath cells, we performed double
      immunohistochemical staining using a standard avidinbiotin complex method with 2
      separate color developing systems. We studied 40 neurofibromas and 16
      neurilemomas. All lesions strongly expressed S-100 in nuclei and cytoplasm. CD34
      was detected in cells having ameboid dendritic cytoplasm present in greatest
      numbers in Antoni B zones of neurilemomas, myxoid zones of neurofibromas, at the
      periphery of lobules in both tumor types, and condensed in apposition to
      perineurium. The CD34+ cells also were detected in normal nerves. They were
      infrequent in Antoni A zones of neurilemomas. No dual S-100 and CD34 expression
      was seen. This double immunostaining confirms the presence of a CD34-reactive non
      Schwannian cell type in these neural neoplasms. As the CD34+, S-100-negative cell
      population is present also in normal nerves and infrequently seen in the areas of
      cellular neoplastic Schwann cells, CD34+, S-100-negative cells in peripheral
      nerve sheath tumors most likely are nonneoplastic and may have a supportive
      function.

PMID- 10884808
TI  - The rise and fall of i-STAT point-of-care blood gas testing in an acute care
      hospital.
AB  - In response to a $350,000 laboratory budget cut and closure of an intensive care
      unit-based laboratory and a desire to maintain turnaround times of 10 minutes or
      less, a multidisciplinary group developed and implemented point-of-care (POC)
      testing. Only blood gases (pH, PO2, and PCO2) and ionized calcium values were
      deemed essential stat tests. Three commercially available POC blood gas devices
      were evaluated; all yielded results comparable to in-house reference methods. The
      1 device with a US Food and Drug Administration-approved method for ionized
      calcium testing and with an existing interface for laboratory information systems
      was selected. Fiscal analysis predicted annual savings of approximately $225,000.
      POC blood gas analysis was implemented in April 1996 coincident with closure of
      the intensive care unit-based laboratory. Clinical laboratories and POC blood gas
      test volumes remained constant through August 1998; in contrast, the number of
      ionized calcium tests decreased dramatically after April 1996. In August 1998,
      clinically significant (i.e., artificial ventilation parameters would have been
      altered based on test results) discrepant PCO2 values were observed sporadically
      and noted only with patient specimens, not with commercial controls or electronic
      simulators. Because investigation failed to identify the cause, use of the POC
      device was discontinued in September 1998.

PMID- 10884809
TI  - A liquid-stable reagent for lactic acid levels. Application to the Hitachi 911
      and Beckman CX7.
AB  - We evaluated the use of a new lactate oxidase-based reagent for the determination
      of serum and plasma lactic acid levels with the Hitachi 911 (Roche Diagnostics,
      Indianapolis, IN) and the Beckman CX7 (Beckman Instruments, Brea, CA). Evaluation
      studies demonstrated on-board stability of at least 3 months and a calibration
      stability of more than 5 months. Within- and between-day imprecision of this
      reagent was less than 2% for both applications. The reagent is free of the
      deleterious effects of triglyceride up to levels of 1,400 mg/dL (15.8 mmol/L),
      bilirubin to concentrations of 24.6 mg/dL (420 mumol/L), and hemoglobin, from
      lysed erythrocytes, to levels of more than 0.3 g/dL (3.0 g/L). When used on the
      Hitachi 911 for the determination of plasma lactate concentrations, the reagent
      correlates with the Dade aca III (Dade International, Deerfield, IL). When
      applied to the Beckman CX7 for the determination of serum lactate levels, the
      method correlates with the Beckman method.

PMID- 10884810
TI  - Replacing the high-cost pathologist.

PMID- 10884811
TI  - Detection of pelvic node metastases.

PMID- 10884812
TI  - Interpreting flow cytometry for hematologic neoplasms.

PMID- 10884813
TI  - Responsible science.

PMID- 10884814
TI  - When should physicians report domestic violence?

PMID- 10884815
TI  - A woman with leg cramps and rash.
AB  - A 68-year-old woman presented with generalized weakness and a rash on her lower
      extremities. The weakness began one week earlier, shortly after treatment for leg
      cramps and two days before the rash appeared. She had also had blood-streaked
      sputum a few days before admission. There was no history of bleeding diathesis,
      nose bleeding, hematuria, vasculitis, muscle or joint aches, cinchonism, or
      exposure to tuberculosis. She denied fever, chills, night sweats, leg pain or
      swelling, chest pain, or abdominal pain.

PMID- 10884816
TI  - Acute coronary syndrome without Q waves.

PMID- 10884817
TI  - Inhaled corticosteroids: 2. Systemic toxicity.

PMID- 10884818
TI  - Macular degeneration: the emerging genetics.
AB  - Discovery of the gene responsible for a recessive, early-onset maculopathy has
      focused attention on a biomolecular pathway in which subtle metabolic flaws
      become toxic to irreplaceable retinal cells. The pathway's identification points
      toward specific ways of intervening. Among patients with age-related macular
      degeneration, carriers of single mutations in the same gene are proving to be
      remarkably common.

PMID- 10884819
TI  - Acute stroke: seeing the full picture.
AB  - Although recent attention has focused on choice of therapeutic agents in stroke,
      optimal management requires a broader view. Moving sequentially from the clinical
      manifestations through brain and then vascular imaging will usually provide the
      precise diagnosis needed to select the most appropriate therapy.

PMID- 10884820
TI  - Managing psychiatric disorders in primary care: 1. Depression.
AB  - Because of their established rapport with patients, primary care physicians are
      in an excellent position to intervene in mild-to-moderate depression and refer
      patients with more severe symptoms for psychiatric evaluation. The key is to
      build a solid therapeutic partnership--by communicating interest, respect,
      support, and empathy for the patient's emotional situation--before turning to the
      prescription pad.

PMID- 10884821
TI  - Withholding or withdrawal of life-sustaining therapy.
AB  - Seventy percent of deaths in intensive care units are preceded by decisions to
      limit life-support, most of which are made in consultation with the patient's
      family or other surrogates. Even when the outcome is clear, surrogates and
      physicians may deny that death is imminent and delay removing ventilatory
      assistance and other supportive measures. To avoid prolonging suffering, end-of
      life decisions should always be guided by the interests and wishes of the
      patient.

PMID- 10884822
TI  - [The double-contrast enema. The Genoa technic between tradition and progress].

PMID- 10884823
TI  - [Images and words. Image transmission and reporting in thoracic radiology (I)].

PMID- 10884824
TI  - [Liver hemodynamic changes, pseudolesions and benign nodular flow-dependent
      lesions. Their pathogenesis and spiral computed tomographic radiological
      aspects].

PMID- 10884825
TI  - [Osteoporosis and phytoestrogens: an assessment of bone mineral density via
      quantitative peripheral computed tomography in milk-egg-vegetarian women in the
      premenopause].
AB  - PURPOSE: Noninvasive assessment of bone mineral density, geometrical and
      biomechanical properties in premenopausal women with dietary intake of
      phytoestrogens and comparison of these parameters with those of age-matched
      female subjects with "Mediterranean" dietary intake lacking in these substances.
      MATERIAL AND METHODS: Volumetric cortical, trabecular and total mineral density
      and bone geometrical properties were evaluated in 15 female subjects with
      phytoestrogens dietary intake. Peripheral quantitative Computed Tomography (pQCT)
      was used to make measurements at the distal radius of the nondominant forearm.
      Fifteen age-matched subjects with "Mediterranean" dietary intake were chosen as a
      control group. Cross-sectional area (Total A), trabecular area (TA), cortical
      area (CA), cortical thickness (CThk) and strength strain index (SSI) were
      assessed as biomechanical parameters. RESULTS: Daily consumption of
      phytoestrogens was significatively different in the two groups (phy: 17.45 mg/die
      vs ctr: 0.35; p < 0.0005), while calcium intake was similar (phy: 652 mg/die vs
      ctr: 650). Total (0.460 g/cm3 vs ctr: 0.433) and trabecular (phy: 0.209 g/cm3 vs
      ctr: 0.189) bone mineral densities, such as SSI (phy: 925 mm3 vs ctr: 894)
      values, were higher in women with dietary intake of phytoestrogens, in comparison
      with the relative controls, but not significantly (p = ns). Among geometrical
      parameters, total area and cortical area were tendential in women with a
      vegetarian diet while cortical thickness was the same in both groups.
      CONCLUSIONS: pQCT showed higher bone mineral density (total and trabecular) and
      SSI values in premenopausal women with dietary intake of phytoestrogens. Despite
      the lack of statistical significance, these preliminary results, should further
      support the few literature findings about the potential role of phytoestrogens
      consumption in preventing trabecular bone loss. However, further studies are
      warranted to evaluate definitively the efficacy of phytoestrogens in preventing
      postmenopausal osteoporosis.

PMID- 10884826
TI  - [Cardiac tomography with 99mTc-tetrofosmin after nitrate administration in
      patients with ischemic cardiopathy and left ventricular dysfunction].
AB  - PURPOSE: To investigate the role of technetium-99m (99mTc) tetrofosmin single
      photon emission Computed Tomography (SPECT) associated with nitrate
      administration in the detection of hypoperfused but still viable myocardium in
      patients with chronic coronary artery disease and left ventricular (LV)
      dysfunction. MATERIAL AND METHODS: Twenty-two patients (mean age 54 +/- 11 years)
      with coronary artery disease, previous myocardial infarction and LV dysfunction
      (LV ejection fraction 38 +/- 13%) were examined. On different days all patients
      underwent 99mTc tetrofosmin (740 MBq) SPECT under control conditions at rest and
      after sublingual nitroglycerin administration (10 mg). Regional tetrofosmin
      activity was quantitatively measured in 22 myocardial segments per patient. In
      each segment, tracer uptake was expressed as a percentage of the region with the
      peak activity. RESULTS: Under control conditions, 267 myocardial segments (55%)
      showed normal tetrofosmin uptake (> 70% of peak activity), 107 segments (22%)
      showed a moderate reduction (51-70%) and 110 segments (23%) a severe reduction (<
      or = 50%) in tracer uptake. Among the 110 segments with a severe reduction in
      tetrofosmin uptake, 20 (18%) showed increased tracer uptake > or = 10% of after
      nitrate administration (from 44 +/- 5% to 58 +/- 3%, p < 0.0001). The remaining
      90 (82%) segments with a severe reduction in tetrofosmin uptake did not show any
      change after nitroglycerin administration (from 38 +/- 9% to 39 +/- 8%, p = ns).
      CONCLUSIONS: In patients with chronic coronary artery disease and LV dysfunction,
      tetrofosmin cardiac SPECT associated with sublingual nitrate administration
      allows the detection of severely hypoperfused but still viable myocardium.

PMID- 10884827
TI  - [The echo-guided interstitial laser photocoagulation of malignant liver tumors.
      The authors' personal technic, immediate results and short-term complications in
      patients with normal and altered liver function].
AB  - PURPOSE: The literature studies about interstitial laser photocoagulation of
      liver tumors mainly deal with the treatment of liver metastasis in patients with
      normal liver function. We report our personal experience with interstitial laser
      photocoagulation in patients with liver tumors (mostly cirrhotics with
      hepatocellular carcinoma). Our aim was to evaluate the short term efficacy of
      percutaneous interstitial laser photocoagulation in inducing focal ablation of
      liver tumors and the possible complications in patients with normal and impaired
      liver function. MATERIAL AND METHODS: Sixty-six patients (52-80 years; 42 men),
      47 with 51 hepatocellular carcinoma nodules (diameter = 1.6-6.6 cm; mean 3.1 cm)
      on cirrhosis (18 in Child-Pugh A class, 24 in B e 5 in C class) and 19 patients
      with single liver metastasis (17 from colon, 2 from lung carcinoma; diameter =
      3.9 cm; mean: 4.5 cm) underwent interstitial laser photocoagulation under
      ultrasound guidance. Depending on tumor size up to four needles were inserted in
      the tumor and multiple laser illuminations were performed: in nodules < or = 2 cm
      a single optical fiber and a single needle insertion were used, in nodules > 2 <
      3 cm, 2-3 fibers were used with a single laser illumination, in nodules > 3 < 4
      cm, 4 fibers were inserted and two laser illuminations were performed in the same
      session after 1.5 cm withdrawal of all fibers in the tumor, in nodules > 4 cm 2
      sessions with 2 laser illuminations per session were performed. Necrosis of the
      nodules was evaluated with triphasic Helical CT 7 days after treatment. Patients
      with incomplete necrosis at CT were treated with additional interstitial laser
      photocoagulation sessions to attain complete necrosis. RESULTS: Fifty-eight
      patients underwent a single interstitial laser photocoagulation session, 7
      patients 2 session and 1 patient 3 sessions. The range of administered energy per
      patient was 1200-32,000 Joules (mean: 6700 J). CT showed complete necrosis of 47
      nodules in 43 patients with hepatocellular carcinoma and in 15/18 patients with
      metastasis. Three Child C class patients with mild ascites and hyperbilirubinemia
      before procedure (nodules O: 1.9, 3.5 and 5.8 cm) dropped out of CT follow-up
      because of severe liver function impairment with increased ascites and
      hyperbilirubinemia, associated with transient ileum paraliticus in 1 case. One of
      these patients died two months after treatment. Two patients with metastasis
      dropped out of treatment because of complications occurred after the interstitial
      laser photocoagulation session (1 ileum paraliticus, 1 gastric hemorrhage) and
      another one refused to continue the treatment.

PMID- 10884828
TI  - [The correlations between color Doppler using a contrast medium and the
      neoangiogenesis of small prostatic carcinomas].
AB  - PURPOSE: To investigate if the use of a contrast agent (Levovist) improves the
      specificity of US in the diagnosis of prostate carcinoma, having the results of
      prostate biopsy as the gold standard. MATERIAL AND METHODS: Thirty patients with
      physical findings suspicious for prostate carcinoma and PSA ranging 5 ng/mL to 15
      ng/mL were examined with transrectal US (TRUS) integrated with the color Doppler
      mode and contrast agent administration (4 g injected at 4 mL/min: 300 mL
      concentration). RESULTS: Based on bioptic and surgical results, 14 prostate
      carcinomas were found, all of them < 1.2 cm. Conventional US recognized the
      suspected nodule in 11 cases, with 78% sensitivity and 93% specificity. Color
      Doppler showed color signals in 8/14 cases, which were peripheral to the lesion
      or intranodular, but did not add any important finding to those of gray-scale US.
      In contrast, contrast enhanced studies showed 13/14 carcinomas, which improved
      sensitivity significantly (92%). Particularly, 11/14 lesions had a typical
      avascular pattern within the strongly enhanced peripheral gland, while 2 small
      lesions only exhibited intranodular vessels. DISCUSSION AND CONCLUSIONS: We
      compared our results with the Microscopic Angiogenesis Grading System (MAGS)
      index and found it exceeded 30 in the 11 avascular lesions value indicates
      microneoangiogenesis. In the other two cases a value < 30 was correlated with a
      different type of tumor vascularization typical of macroangiogenesis.

PMID- 10884829
TI  - [A rare case of an aneurysmal cyst of the rib. A study by traditional radiology,
      computerized axial tomography and magnetic resonance].

PMID- 10884830
TI  - [A subcoracoid leiomyoma in a patient with diagnosed AIDS. A case report and
      review of the literature].

PMID- 10884831
TI  - [Breast lipomas in echography. A discussion of 3 cases and a review of the
      literature].

PMID- 10884832
TI  - [Lymphangioleiomyomatosis. The computed tomographic aspects in an early case].

PMID- 10884833
TI  - [A septic embolism and mycotic pseudoaneurysm of the superior mesenteric artery
      in a patient with enterococcal endocarditis. Their diagnosis by computed
      tomography and magnetic resonance angiography].

PMID- 10884834
TI  - [An ulcer of the pyloric canal in a nursing infant].

PMID- 10884835
TI  - [A meta-traumatic rupture of a splenic teratoma. A case report].

PMID- 10884836
TI  - [Bilateral renal agenesis: a case studied by color Doppler].

PMID- 10884837
TI  - [Postoperative hyperthyroidism. The diagnostic and therapeutic role of nuclear
      medicine].

PMID- 10884838
TI  - [An isolated adrenal hematoma due to closed abdominal trauma studied by
      echography].

PMID- 10884839
TI  - [Neonatal adrenal hemorrhage associated with a scrotal hematoma. A case report].

PMID- 10884840
TI  - [Suggestions from a quarter moon].

PMID- 10884841
TI  - [Thoracic radioscopy and literature: a chance encounter].

PMID- 10884842
TI  - From form to meaning: a role for structural alignment in the acquisition of
      language.

PMID- 10884843
TI  - The role of essentialism in children's concepts.

PMID- 10884844
TI  - Infants' use of prior experiences with objects in object segregation:
      implications for object recognition in infancy.

PMID- 10884845
TI  - Perseveration and problem solving in infancy.

PMID- 10884846
TI  - Temperament and attachment: one construct or two?
AB  - In this chapter we described the constructs of temperament and attachment and
      have discussed similarities and differences between the two. We addressed the
      issue of whether temperament contributes to overall attachment security or to the
      specific type of attachment that children display. We conclude that although
      temperament may influence the type of secure and insecure attachment relationship
      children form with their parent, temperament alone will not determine if a child
      is classified as securely or insecurely attached. We presented evidence
      suggesting that certain dimensions of temperament, specifically negative
      emotionality, may be associated with infants' behavior during the Strange
      Situation, such as proneness-to-distress during separations. However, we noted
      that these temperament dimensions do not predict overall security of attachment.
      It is likely that although no single temperament characteristic, such as
      proneness-to-distress, in and of itself determines overall attachment security,
      it is possible that a constellation of temperament characteristics may be more
      strongly related to attachment security. The examination of constellations of
      temperament characteristics may be particularly useful for furthering our
      understanding of individual differences within attachment classifications. Such
      an approach may elucidate the reasons why infants are classified into one
      subgroup of secure, insecure-avoidant, or insecure-resistant attachment versus
      another subgroup. Furthermore, we suggest that the collection of findings
      regarding temperament and attachment not only underscores the importance of a
      transactional approach to early social-emotional development, but emphasizes that
      temperament and attachment can make unique and interactive contributions to
      children's social-emotional functioning. That is, the goodness-of-fit between
      infant and parent characteristics may best predict security of attachment.
      Although child characteristics clearly contribute to the development of the
      parent-child relationship, we believe that the effects of infant temperament on
      infant-caregiver attachment may well be indirect, and may be moderated by such
      variables as maternal personality and social support. Thus, taken together, a
      growing literature clearly indicates that although temperament and attachment
      security are interrelated, they are by no means interchangeable constructs. To
      return to our guiding question, "Temperament and attachment: One construct or
      two?" We reply, "two."

PMID- 10884847
TI  - The foundation of Piaget's theories: mental and physical action.
AB  - Piaget's late theory of action and action implication was the realization of a
      long history of development. A review of that history shows the central place of
      action in all of his theoretical assertions, despite the waxing and waning of
      other important features of his theories. Action was said to be the primary
      source of knowledge with perception and language in secondary roles. Action is
      for the most part not only organized but there is logic in action. Action, which
      is at first physical, becomes internalized and transformed into mental action and
      mental representation, largely in the development of the symbolic or semiotic
      function in the sensorimotor period. A number of alternative theories of
      cognitive development place primary emphasis on mental representation. Piaget
      provided it with an important place as well, but subordinated it to mental action
      in the form of operations. In this, as Russell claims, he paralleled
      Schopenhauer's distinction between representation and will. Piaget's theory of
      action was intimately related to the gradual development of intentionality in
      childhood. Intentions were tied to actions by way of the conscious awareness of
      goals and the means to achieve them. Mental action, following the sensorimotor
      period, was limited in its logical form to semilogical or one-way functions.
      These forms were said by Piaget to lack logical reversibility, which was achieved
      only in the sixth or seventh year, in concrete operations. Mental action was not
      to be fully realized until the development of formal operations, with
      hypothetical reasoning, in adolescence, according to the classical Piagetian
      formulation. This view of the child's logical development, which relied heavily
      on truth-table (extensional) logic, underwent a number of changes. First from the
      addition of other logics: category theory and the theory of functions among them.
      In his last theory, however, an even more radical change occurred. With the
      collaboration of R. Garcia, he proposed a logic of meanings that would require a
      recasting of his earlier truth-table-based operatory logic that he claimed
      explained the development of logical thought and problem solving. The new logic
      of meanings, influenced by Anderson and Belnap's (1975) logic of entailment,
      placed new emphasis on inferential processes in the sensorimotor period,
      introduced protological forms in the actions of the very young child, and
      proposed that knowledge has an inferential dimension. The consequence was that
      the late theory shifted emphasis to intentional (qualitative) logic and meaning
      from the earlier extensional (quantitative) logic and truth testing. The profound
      changes in Piaget's late theory requires a serious reevaluation of Piaget's
      entire corpus of research and theory; a task which is yet to be done. Seen in a
      new light, the late theory is much closer to intellectual currents associated
      with hermeneutic and semiotic traditions in their concern with meaning and
      interpretation and less, if at all, with truth. This, despite Piaget's couching
      of the new theory in a logical mode. The late theory added significant new
      elements to the theory of action and action-implication, and suggest that
      Piaget's, and his collaborator's, new research data, which were interpreted
      within the new theoretical framework, require corroboration and review. The
      question as to whether Piaget's assertions are at root metaphorical and lack
      psychological reality, which has followed his theories from its earliest days,
      arises as well with the assertions of the late theory. Possibly, even more so,
      since even a limited historical review of his theories points to a considerable
      concurrence between changes in the fundamental assumptions of his theories and
      intellectual currents of the times. In hindsight, Piaget's theories appear as
      "works in progress," down to his last theory. Yet, even in the end, he charted
      the direction of possible further progress.

PMID- 10884848
TI  - Paranasal sinuses.

PMID- 10884849
TI  - Low-fat milk.

PMID- 10884850
TI  - Laxatives.

PMID- 10884851
TI  - Germ wars.

PMID- 10884852
TI  - Rational use of antibiotics in an era of emerging resistance.

PMID- 10884853
TI  - Principles of antibiotic use for the treatment of bacterial infection.

PMID- 10884854
TI  - Antimicrobial therapy for ambulatory pediatrics.

PMID- 10884855
TI  - The mechanisms and the spread of antibiotic resistance.

PMID- 10884856
TI  - Antibiotic use and abuse in clinical practice.

PMID- 10884857
TI  - Meeting the challenge of antibiotic resistance: an evidence-based approach to
      treatment.

PMID- 10884858
TI  - The changing clinical features of HIV-1 infection in the United Kingdom.
AB  - Despite advances in antimicrobial and anti-retroviral treatment in the past
      decade, the natural history of HIV-1 infection remains largely unchanged.
      Clinical monitoring has led to the introduction of effective prophylaxis of
      Pneumocystis carinii pneumonia and has facilitated the early detection and
      treatment of opportunistic infections. Pneumocystis carinii pneumonia now makes
      up a smaller proportion of first AIDS defining diagnoses than before prophylaxis
      was introduced. The proportion made up by more unusual opportunistic infections
      and malignancies, that occur later in the course of the disease, is growing. Late
      stage HIV disease--which is now complicated by infections with organisms of low
      pathogenicity, often combined with systemic Kaposi's sarcoma or lymphoma-
      presents major problems in clinical management. Further changes in the clinical
      features of HIV-1 infection may be expected in the future as more effective
      antimicrobial and anti-retroviral treatments are developed.

PMID- 10884859
TI  - Food poisoning at a Masonic lodge.

PMID- 10884860
TI  - Apple pie: an unusual vehicle for food poisoning.

PMID- 10884861
TI  - Food poisoning associated with a self-catered wedding reception.

PMID- 10884862
TI  - 'Corynebacterium ulcerans': a potential cause of diphtheria.
AB  - Symptoms similar to those of diphtheria may occasionally be caused by micro
      organisms other than Corynebacterium diphtheriae, such as zoonotic
      corynebacteria. A case of pharyngitis caused by toxigenic 'C. ulcerans' in a 9
      year old girl illustrates the importance of including diphtheroids in the
      differential diagnosis. The presenting symptoms may have been attenuated by
      previous immunisation against C. diphtheriae. 'C. ulcerans' should be considered
      in the differential diagnosis of pharyngitis, especially in patients with a
      history of contact with farm animals or the consumption of raw dairy products.

PMID- 10884863
TI  - Diagnosis of childhood pneumonia in the tropics.
AB  - Recent global estimates indicate that there are 10 million deaths annually of
      children aged < 5 years and that 99% of these deaths occur in developing
      countries, with 70% caused by infections. Pneumonia is the leading cause of the
      infection-attributable mortality in this age-group, accounting for > 2 million of
      the deaths. These deaths are potentially preventable if appropriate clinical and
      laboratory tools are in place to facilitate early detection of the pneumonia,
      identification of the pathogen involved, and institution of appropriate therapy
      or, even better, implementation of appropriate vaccination schedules. The
      currently available tools for the diagnosis of acute, lower-respiratory-tract
      infections in children have low sensitivity and are, in any case, grossly
      underutilized. Consequently, there is a great shortage of the data necessary for
      implementing potentially effective, intervention measures. This review is of the
      common aetiological agents of childhood pneumonia in the tropics and of the
      clinical and laboratory techniques currently available for routine diagnosis.
      Although there are newer and more sensitive diagnostic tools, they are expensive
      and are not likely to be within reach of most developing countries in the
      tropics. There is, however, considerable scope to improve the use of the cheaper
      techniques, and so facilitate the development and implementation of effective
      control measures.

PMID- 10884864
TI  - Comparative efficacy of chloroquine plus chlorpheniramine alone and in a
      sequential combination with sulfadoxine-pyrimethamine, for the treatment of
      acute, uncomplicated, falciparum malaria in children.
AB  - One hundred and eight children with acute, symptomatic, uncomplicated, falciparum
      malaria were randomized to receive chloroquine (for 3 days) plus chlorpheniramine
      alone (for seven days) (CQ-CP group; N = 55) or, in a sequential treatment,
      chloroquine plus chlorpheniramine for 3 days followed, on the fourth day, by a
      single oral dose of sulfadoxine-pyrimethamine (25 mg sulfadoxine/kg) (CQ-CP-SP
      group; N = 53). The mean (S.D.) parasite-clearance time in the CQ-CP group [2.1
      (0.7) days; range = 1-5 days] was similar to that in the CQ-CP-SP [2.1 (0.8)
      days; range = 1-5 days]. The fever-clearance times were also similar: 1.2 (0.1)
      days (range = 1-3 days) v. 1.1 (0.4) days (range = 1-3 days). The cure rates on
      days 14, 21 and 28 were 98.2%, 96.3% and 92.7%, respectively in the CQ-CP group,
      and 100%, 100% and 96.2%, respectively, in the CQ-CP-SP group. The rates of
      gametocyte carriage were low and similar (5.4% in the CQ-CP group and 3.8% in the
      CQ-CP-SP group) throughout the duration of the study. Both treatment regimens
      were relatively well tolerated, the main adverse reactions being similar:
      sleepiness (on day 1) and pruritus (on days 1-3). No adverse effect was
      attributable to SP. The results indicate that sequential treatment, for 3 days
      with CQ and CP, followed by a single dose of SP, is effective and well tolerated
      in children with acute, uncomplicated, falciparum malaria and may be an
      alternative treatment for CQ- and/or SP-resistant falciparum malaria. Treatment
      with a CQ-CP combination (CQ and CP for 3 days and then CP alone for another 4
      days) is also effective but requires continuing administration after the signs
      and symptoms of acute malaria have disappeared.

PMID- 10884865
TI  - The resistance to physiological shear stresses of the erythrocytic rosettes
      formed by cells infected with Plasmodium falciparum.
AB  - Rosetting forces are believed to be an important contributor to the
      microcirculatory obstruction that occurs in malaria caused by Plasmodium
      falciparum. In this study, rosettes of erythrocytes from cultures of this
      parasite were suspended in different media and exposed to shear stresses
      corresponding to those encountered on the arterial and venous sides of the human
      circulation. The rosettes formed by infected erythrocytes in malaria culture
      medium containing 10% AB serum were disrupted easily (approximately 50% being
      broken) when exposed to very low shear stresses of < 0.5 Pa. However, use of
      higher concentrations of serum strengthened the rosetting binding forces
      considerably. Suspension of rosettes in a viscous colloid (e.g. dextran)
      increased the adherence forces between infected and uninfected red cells. The
      results indicate that rosettes do resist the physiological shear forces that are
      encountered in the venular side of the circulation and could thus contribute to
      microvascular obstruction in falciparum malaria.

PMID- 10884866
TI  - Comparison of blood-film microscopy, the OptiMAL dipstick, Rhodamine-123
      fluorescence staining and PCR, for monitoring antimalarial treatment.
AB  - In an attempt to see if the OptiMAL dipstick (Flow Inc., Portland, OR) can be
      used to monitor antimalarial treatment, a pilot study of 17 patients with
      Plasmodium falciparum malaria, admitted to the Hospital for Tropical Diseases in
      London, U.K., was conducted. Sequential, follow-up, blood specimens were obtained
      from day 1 to day 3, 4 or 5 post-admission. Thin and thick films prepared from
      these samples were examined for the presence of malarial parasites, and the
      intensities of parasitaemia were estimated. In addition, each specimen was tested
      with the OptiMAL dipstick, Rhodamine-123 fluorescence staining and, on specimens
      collected on day 1 and the last follow-up before discharge, by a PCR-based test.
      The results showed that OptiMAL has good sensitivity for the initial diagnosis of
      P. falciparum malaria and also mirrors the decline in viability of the parasites
      on treatment, giving the potential to follow the efficacy of drug treatment. The
      results of the PCR-based tests were still positive when the blood film and
      OptiMAL result were negative. The OptiMAL dipstick compared well with blood-film
      microscopy for monitoring antimalarial treatment and could be a useful
      replacement for microscopy to monitor treatment in places where facilities for
      microscopy are either lacking or inadequate. In developed countries it could be a
      useful adjunct to blood-film microscopy, and it might permit a reduction in the
      duration of hospitalization and give an early warning of treatment failure.

PMID- 10884867
TI  - A nested, multiplex, PCR assay for the simultaneous detection and differentiation
      of Entamoeba histolytica and Entamoeba dispar in faeces.
AB  - The detection of and differentiation between Entamoeba histolytica and Entamoeba
      dispar are of great importance, both for diagnosis and for epidemiological
      studies. Most PCR-based methods for the discrimination of these two species
      employ complex procedures for DNA extraction and require different protocols for
      E. histolytica and E. dispar, leading to relatively high expenditure, labour
      costs and turnaround times. A simple, rapid, cost-effective and yet sensitive and
      specific multiplex PCR technique has now been developed for the simultaneous
      detection and differentiation of E. histolytica and E. dispar in faecal samples.
      The detection limit is 200 trophozoites of E. dispar or 1000 trophozoites of E.
      histolytica/g stool sample. The sensitivity of the assay remains practically
      unchanged, even in the presence of 20,000 trophozoites of the other species/g
      stool sample. Thus, this technique may also easily reveal mixed infections,
      without the danger of misdiagnosis caused by one strain displacing the other in
      culture.

PMID- 10884868
TI  - A cross-sectional survey to analyse the risk factors associated with human cystic
      echinococcosis in an endemic area of mid-Wales.
AB  - In mid-Wales, the prevalence of cystic echinococcosis (hydatid disease) in humans
      and other animals has been well documented. A cross-sectional study was therefore
      undertaken to examine the associated demographic and environmental risk factors
      for the disease in humans, in Powys, mid-Wales. Overall, 223 fully completed
      questionnaires were returned from a postal survey. Eighteen of the respondents
      had been treated for cystic echinococcosis (CE). No significant association was
      found between many of the well-established risk factors, such as dog or farm
      ownership, and treatment for CE, although women were more likely to have been
      treated for the disease than men.

PMID- 10884869
TI  - The occurrence of polycystic echinococcosis in Suriname.
AB  - The occurrence of polycystic echinococcosis (PE) caused by Echinococcus vogeli in
      Suriname is reviewed. Six of the eight known cases, including the first (which
      was incorrectly diagnosed as cystic hydatid disease caused by E. granulosus) in
      1982, are described. The distribution in Suriname of the natural hosts of E.
      vogeli--the bush dog (Speothus venaticus) and the paca (Agouti paca)--is
      discussed. Characteristics of the four species recognized in the genus
      Echinococcus are compared, and all known cases of PE in 11 countries in the
      Neotropics are summarized. Finally, it is stressed, that, in Suriname, PE should
      be considered during the differential diagnosis of all subjects from rural areas
      who present with abdominal pain and palpable, intraperitoneal masses.

PMID- 10884870
TI  - A comparison of newer tests for the diagnosis of onchocerciasis.
AB  - Samples of human serum, skin and urine, collected in Cameroon, were used to
      assess the value of some newer methods for the diagnosis of onchocerciasis.
      Parasite DNA was detected in skin snips and urine by PCR, and parasite antigen
      was detected in serum and urine by immunoblotting. Serum concentrations of IgG4
      antibodies reacting with recombinant Onchocerca volvulus antigens (OC3.6 and
      OC9.3) were also measured, using an ELISA. The PCR-based tests of skin snips and
      the serological tests for antigen and antibody tests showed higher sensitivities
      (90%-100%) than the urine PCR (14%) or the urine antigen test (68%). Although
      antibody detection is much easier to perform than tests based on PCR or antigen
      detection, the latter have an advantage in that they are only positive in people
      with current infections. Thus, antibody testing may be more useful for screening
      populations for infection or exposure to O. volvulus, whereas PCR and antigen
      testing are potentially more useful for diagnosis of infections in individuals
      and for monitoring the success of therapy.

PMID- 10884871
TI  - Specific and total IgE in patients with recurrent, acute urticaria caused by
      Anisakis simplex.
AB  - Titres of parasite-specific IgE were investigated in 19 patients thought to have
      recurrent, acute urticaria caused by sensitization to Anisakis simplex (Dujardin,
      1845), before and after they were placed on a fish-free diet. Patients with other
      allergic disease and those being treated with corticosteroids or antihistaminics
      were excluded. Skin-prick tests were carried out with A. simplex extract, and
      blue- and white-fish extracts. The CAP system (Pharmacia), a commercial test kit
      developed for the assay of food-specific IgE, was used to monitor serum
      concentrations of total IgE and antigen-specific IgE against Anisakis, Ascaris,
      Echinococcus, Toxocara, tuna, salmon, shrimp, mussel and cod. Before going on a
      fish-free diet, the 19 patients had CAP scores against A. simplex of 5 (three
      cases), 3 (seven) or 2 (nine). After a mean of 120 days on the diet, the scores
      against A. simplex were unchanged in 15 of the cases, reduced in three [from 5 to
      4 (one case) or from 2 to 0 (two cases)] and increased in one (from 2 to 3). Most
      (16) of the patients no longer had any urticaria and the others reported
      significant reductions in the intensity and frequency of their symptoms.

PMID- 10884872
TI  - Epidemiology of infections with intestinal parasites and human immunodeficiency
      virus (HIV) among sugar-estate residents in Ethiopia.
AB  - Intestinal parasitic infections could play an important role in the progression
      of infection with human immunodeficiency virus (HIV), by further disturbing the
      immune system whilst it is already engaged in the fight against HIV. HIV and
      intestinal parasitic infections were investigated in 1239, randomly selected
      individuals, aged 15-54 years, living on a sugar estate in central Ethiopia.
      Intestinal parasites were identified in faecal samples (one/subject) using
      direct, concentration, and (for Strongyloides stercoralis larvae) Baermann
      methods. HIV serological status was determined using ELISA, with ELISA-positive
      samples confirmed as positive by western blotting. Most (70.1%) of the subjects
      were infected with at least one intestinal parasite and 3.1% were seropositive
      (but asymptomatic) for HIV. The intestinal parasites identified in the study
      population were amoebic parasites (Entamoeba histolytica/Enta. dispar) (24.6%),
      hookworms (23.8%), Ascaris lumbricoides (22.2%), Trichuris trichiura (19.5%), S.
      stercoralis (13.0%), Taenia saginata (4.5%), Giardia lamblia (3.0%), and
      Enterobius vermicularis (1.3%). Overall, the HIV-positives were no more or less
      likely to carry intestinal parasites than the HIV-negatives (76.2% v. 69.9%; P >
      0.05). However, when each parasite was considered separately, amoebic parasites
      were found to be more common in the HIV-positives than the HIV-negatives (43.7%
      v. 24.0%; P < 0.05). This difference remained significant in a multivariate
      analysis, after controlling for the socio-demographic characteristics of the
      study participants. In conclusion, there was moderate interaction between
      intestinal parasites and HIV at the asymptomatic stage of HIV infection. The
      observed association between amoebic and HIV infections requires confirmation in
      a prospective study, allowing for the analysis of biological mechanisms involved
      in the association.

PMID- 10884873
TI  - The cytotaxonomy of Simulium damnosum s.l. (Diptera: Simuliidae) from the Thyolo
      onchocerciasis focus in Malawi and description of a new member of the complex.
AB  - Larvae of the Simulium damnosum complex were collected in southern Malawi, in
      particular from the Thyolo onchocerciasis focus. Cytological identifications
      revealed the occurrence of S. (Edwardsellum) thyolense sp.nov., S. kilibanum
      Gouteux, 'Ketaketa', a new cytoform tentatively designated 'Mwamphanzi', and two
      unassigned specimens. Simulium thyolense sp.nov. is presumably the major vector
      of Onchocerca volvulus in the area, but it remains possible that the other
      cytospecies are secondary vectors. Simulium thyolense sp.nov. is most
      appropriately classified near the 'Sanje' subcomplex, whereas 'Mwamphanzi' and
      the unassigned specimens are members of the 'Ketaketa' subcomplex.

PMID- 10884874
TI  - PCR-RFLP analysis of Cryptosporidium parvum isolates from HIV-infected patients
      in Lisbon, Portugal.

PMID- 10884876
TI  - Editorial announcement

PMID- 10884875
TI  - Rapid assessment of the prevalence and distribution of lymphatic filariasis in
      Sierra Leone.

PMID- 10884877
TI  - The management of neurosurgical patients with postoperative bacterial or aseptic
      meningitis or external ventricular drain-associated ventriculitis. Infection in
      Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy.

PMID- 10884878
TI  - The comparative efficacy of intravenous cefotaxime and
      trimethoprim/sulfamethoxazole in preventing infection after neurosurgery: a
      prospective, randomized study. Brisbane Neurosurgical Infection Group.
AB  - The objective of the investigation was to determine the comparative efficacy of
      cefotaxime versus trimethoprim-sulfamethoxazole in the prophylaxis of patients
      undergoing neurosurgical procedures. In this prospective randomized open study,
      780 adult patients undergoing elective craniotomy, shunt surgery or stereotactic
      surgery were randomized to receive preoperative cefotaxime (1 g) or trimethoprim
      sulfamethoxazole (160 mg trimethoprim, 800 mg sulfamethoxazole) as prophylaxis:
      613 patients were available for analysis, of whom 315 received cefotaxime and 298
      received trimethoprim-sulfamethoxazole. Forty-two patients (6.9%) experienced 49
      postoperative infections, with no significant difference between treatment
      groups. The most common infections unrelated to neurosurgery were urinary tract
      infections (17 cases) and pneumonia (seven cases). Fifteen neurosurgical
      infections occurred, comprising 11 wound infections, two shunt infections and two
      cerebral abscesses. Neurosurgical infection rates were similar in the cefotaxime
      group (2.5%) and the trimethoprim-sulfamethoxazole group (2.3%). We concluded
      cefotaxime and trimethoprim-sulfamethoxazole administered as single dose prior to
      neurosurgery are equally effective in controlling neurosurgical infection and
      postoperative infection at remote sites.

PMID- 10884879
TI  - Management of tuberculomas of the craniovertebral junction.
AB  - Tuberculosis of the craniovertebral junction is extremely rare. However, recent
      evidence suggests that the incidence of this condition may be increasing in the
      United Kingdom. The diagnosis is often difficult despite advances in imaging
      using MRI. CT guided biopsy of lesions often yields inconclusive results. The
      transoral approach to the anterior craniovertebral junction provides excellent
      access to this region with a low operative morbidity and mortality, enabling
      biopsy of lesions and decompression of the neuraxis. Management of secondary
      atlantoaxial instability, regarding both timing and method of stabilization, is
      controversial. We report two cases of tuberculomas of the craniovertebral
      junction, that illustrate the role of transoral surgery in both diagnosis and
      treatment of this condition. Previous management strategies are reviewed and
      future recommendations are presented.

PMID- 10884880
TI  - Microvascular decompression for trigeminal neuralgia: report of outcome in
      patients over 65 years of age.
AB  - Microvascular decompression (MVD) is now recognized as an effective operation for
      the cure of trigeminal neuralgia (TN), and is far superior to the other surgical
      procedures utilized in the treatment of TN. TN is common in the elderly, but
      there is debate concerning MVD in 'elderly' patients. Some clinicians have a
      policy of not offering patients over a certain age the choice of MVD, yet the
      recurrence rate is inversely related to the age of the patient. Previous failed
      procedures and a long period of pain before MVD, also affect the outcome
      negatively. This study is a retrospective review of the outcome in elderly
      patients following MVD. Forty-two patients over the age of 65 years are reviewed
      after undergoing MVD for TN. The results indicate that there was no serious
      morbidity or mortality that could be ascribed to old age and the length of stay
      in the hospital was not influenced by the age of the patient. The results are
      compared with the outcome in a younger age group and the literature on MVD for TN
      reviewed.

PMID- 10884881
TI  - Expression of p19INK4d, CDK4, CDK6 in glioblastoma multiforme.
AB  - Deregulation of the G1/S checkpoint is a frequent event in the development of
      glioblastoma multiforme (GBM). Previous studies have shown more than 50% of
      primary GBM tumours contain either complete loss of the p16INK4a locus or
      amplification of the CDK4 gene. Moreover, many heterozygosity studies have shown
      deletion on human chromosome 19p13.2, where the p19INK4d gene has been localized.
      We examined the expression of p19INK4d and its two CDK substrates in a series of
      glioma-derived cell lines and tumours. No gene rearrangement or deletion was
      observed in the p19INK4d gene in these cell lines; however, expression of CDK4
      and CDK6 was elevated relative to matched normal brain tissue in eight of 18 GBM
      tumours (44%). Furthermore, CDK6 expression level was increased in 12/14
      glioblastomas, but undetectable in tumour samples of a previous lower grade
      tumour from the same patient. These data attest to the functional importance of
      both CDK4 and CDK6 in astrocytic tumourigenesis, particularly during the later
      stages of tumour progression.

PMID- 10884882
TI  - Bilateral trigeminal neuralgia: a therapeutic dilemma.
AB  - In order to illustrate the inherent problems of managing bilateral trigeminal
      neuralgia a retrospective study of the 16 cases of bilateral trigeminal
      neuralgia, out of just over 300 cases of trigeminal neuralgia, treated over a 14
      year period, has been performed. All the patients, presented with a typical
      history of trigeminal neuralgia and underwent surgical exploration. Pain relief
      was initially achieved in all cases; however, only four remained cured, three
      have become pain free after additional rhizotomy, a further one after peripheral
      cryotherapy and four with medical treatment. Four patients have had bilateral
      operations for trigeminal neuralgia, but in two cases the pain was relieved on
      one side only. Bilateral trigeminal neuralgia presents special problems of
      management with respect to underlying neuropathology (e.g. multiple sclerosis),
      the need for the limitation of the use of ablative techniques in order to
      minimise the disability of bilateral sensory and motor dysfunction, and the
      relatively poor response to microvascular decompression. These factors emphasize
      the multifactorial nature of the cause of trigeminal neuralgia. Magnetic
      resonance tomographic angiography is now available and is important in
      determining the range of therapeutic options for this group of patients.

PMID- 10884883
TI  - Results of posterior cervical foraminotomy for treatment of cervical spondylitic
      radiculopathy.
AB  - We evaluated the results of posterior cervical foraminotomy for spondylitic
      radiculopathy using a questionnaire sent to all 77 patients who had undergone
      surgery between 1990 and 1995 at our institution. Sixty-two patients (40 male)
      returned their questionnaires, one of whom had undergone two procedures (dealt
      with as separate events). Sixty patients complained of pre-operative arm pain; of
      these 42 (70%) had complete or > 75% resolution of their pain, 14 (23%) had < 75%
      improvement in their pain and four (7%) had the same or worsened pain at the time
      of the questionnaire. Sixteen patients (27%) reported initial improvement in
      symptoms with subsequent deterioration. The mean patient satisfaction score using
      a linear analogue scale from 0 to 10 was 7.5. Main postoperative complaints were
      neck pain (22%), persisting motor deficit (6%) and persisting sensory deficit
      (9%). One patient suffered nerve root damage at surgery. For unilateral and, in
      some cases, multi-level degenerative disease causing cervical radiculopathy,
      posterior cervical foraminotomy is a useful technique with the advantage of
      avoiding fusion, immobilization and the long-term risk of instability.

PMID- 10884884
TI  - Immediate postoperative CT to assess the correct positioning of a ventricular
      catheter.
AB  - Positioning of the ventricular catheter is safe using standard techniques, but in
      some cases there may be failure of a shunt because of incorrect placement. We
      carried out CT at the end of the surgical operation on 10 patients who had
      undergone cerebrospinal fluid shunting while still anaesthetized. In three cases
      a malpositioned catheter was detected. Immediate reoperation allowed readjustment
      of the ventricular catheter. Early postoperative CT appears to be useful for
      verifying correct placement.

PMID- 10884885
TI  - A new cranial access device for cerebral monitoring.
AB  - We report the design and clinical application of a new cranial access device
      (triple bolt) designed to transmit intracranial pressure monitors, multiparameter
      sensors, microdialysis catheters and laser doppler probes into the cerebral
      parenchyma. The objective was to achieve insertion on the Neuro-Critical Care
      Unit, imaging compatibility, angled trajectories and versatility of monitor
      application. The bolt has been successfully applied to 100 patients with severe
      head injury and subarachnoid haemorrhage.

PMID- 10884886
TI  - Transnasal endoscopic repair of cerebrospinal fluid rhinorrhoea.
AB  - The complications associated with the employment of neurosurgical techniques for
      the management of cerebrospinal fluid rhinorrhoea has led to the development of
      extracranial approaches. The nasal endoscope can be used to improve visualisation
      of the site of the leak and to facilitate free graft or septal flap placement.
      This ensures a high rate of dural defect healing with minimal morbidity. This
      study describes four cases with CSF fistulas that were repaired endoscopically
      and the specific surgical techniques that were used. The authors believe that, in
      carefully selected cases, transnasal endoscopic management of CSF leaks can be
      the initial surgical treatment of choice.

PMID- 10884887
TI  - Primary Ewing's sarcoma of the greater wing of the sphenoid bone.
AB  - Primary Ewing's sarcoma is an uncommon lethal tumour of the long bones and pelvic
      girdle mainly affecting children and young adults. An origin in the cranial bones
      is extremely rare. We report a unique case of primary involvement of the greater
      wing of sphenoid bone in a 16-year-old patient. Aggressive management using
      microsurgical resection, radiotherapy and chemotherapy was curative. Localized,
      primary Ewing's sarcoma of the cranial bones should be considered as a distinct
      clinicopathological entity with an extremely low rate of dural penetration and
      metastases, and with a relatively better prognosis as compared with those of long
      bones and pelvic girdle. In neurosurgical practice, primary Ewing's sarcoma of
      the cranial bones requires early aggressive management to achieve adequate long
      term prognosis and cure.

PMID- 10884888
TI  - Cavernous haemangioma of cavernous sinus associated with an internal carotid
      artery aneurysm.
AB  - A 50-year-old woman developed a sudden onset of ophthalmoplegia. CT and MRI
      showed a massive middle cranial fossa tumour encasing the intracavernous sinus
      carotid artery. The tumour extended into Meckel's cave and sella, and had eroded
      the lateral wall of the orbit. Angiography showed a faint tumour blush and an
      aneurysm of the distal part of cavernous segment of internal carotid artery. On
      exploration, an extremely vascular, entirely intracavernous sinus cavernous
      haemangioma was completely excised and the aneurysm was clipped. The literature
      on this relatively rare and surgically formidable condition is reviewed.

PMID- 10884889
TI  - CNS granulomatosis in a child with chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a disease in which a granulomatous process
      involves various organ systems and in which recurrent infections are seen. The
      basic defect is the absence of the granulocyte respiratory burst. CNS involvement
      is rare. We present a report of a child with CGD and CNS involvement, presenting
      with hydrocephalus. Candida was identified in the granulomata. The patient
      responded well to a CSF shunt and antifungal therapy.

PMID- 10884890
TI  - Symptomatic bilateral xanthogranulomas of choroid plexus in a child.
AB  - Choroid plexus xanthogranulomas are uncommon lesions that occur almost
      exclusively in adults; most of them constitute incidental autopsy findings. A
      case of symptomatic bilateral xanthogranulomas of choroid plexus in a 6 year-old
      girl with progressive visual loss is reported. Theories on the pathogenesis of
      this entity are reviewed.

PMID- 10884891
TI  - Post-traumatic malignant glioma: case report and review of the literature.
AB  - Posttraumatic gliomas have been described, but in none of these has there been
      documented evidence of absence of tumour at the time of the injury. We report a
      case of post-traumatic malignant glioma with radiological evidence of only a
      contusion prior to the development of the tumour.

PMID- 10884892
TI  - Pharyngo-cutaneous fistula following anterior cervical fusion.

PMID- 10884893
TI  - Topical antibiotics in neurosurgery: a re-evaluation of the Malis technique.

PMID- 10884894
TI  - Genetics of novel therapeutic targets in schizophrenia.

PMID- 10884895
TI  - Behavioural pharmacology of the new generation of antipsychotic agents.
AB  - In conclusion, the newer agents all have behavioural profiles which can be
      clearly differentiated from those of the older, classical agents. Behavioural
      data indicate that to a greater or lesser extent, all the newer antipsychotics
      will produce fewer acute EPS than the older agents. However, the new 'atypical'
      agents all have distinct profiles. Olanzapine has a profile similar to that of
      clozapine, albeit somewhat more potent. Olanzapine, like clozapine, displays a
      wide margin between the doses predictive of efficacy and those which induce EPS.
      The compound also substitutes for clozapine in drug discrimination assays and
      increases punished responding in a conflict paradigm. Quetiapine also has a
      clozapine-like profile, although it lacks the cholinergic receptor affinity and
      is relatively weak in most behavioural assays. Quetiapine, like olanzapine, also
      reverses PCP-induced deficits, and substitutes for clozapine in drug
      discrimination assays. However, no data are currently available regarding
      quetiapine's action in anxiolytic tests. Risperidone, sertindole and ziprasidone
      have profiles of activity different from those of older agents, predominantly due
      to their 5-HT2a affinity. All these agents possess some properties similar to
      those of clozapine, but there are some differences: for example, risperidone and
      sertindole fail to substitute for clozapine in drug discrimination assays and are
      inactive in classical conflict models of anxiety. It is more difficult to make an
      accurate assessment of the behavioural profile of ziprasidone, due to a lack of
      published data. Given the behavioural differences exhibited by animals receiving
      the new antipsychotic agents, one would predict that these drugs will have
      distinct clinical profiles. All the agents display activity indicative of agents
      with a reduced propensity to induce EPS. However, significant differences may be
      observed in their efficacy against negative and cognitive symptoms. It will be
      important to assess the clinical profiles of these agents carefully if the
      predictive value of the pre-clinical 'models' is to be improved.

PMID- 10884896
TI  - Neurochemical alterations in schizophrenia affecting the putative receptor
      targets of atypical antipsychotics. Focus on dopamine (D1, D3, D4) and 5-HT2a
      receptors.

PMID- 10884897
TI  - In vivo neuropharmacology of schizophrenia.

PMID- 10884898
TI  - Critical analysis and comparison of the side-effect and safety profiles of the
      new antipsychotics.

PMID- 10884899
TI  - Cognitive effects of conventional and atypical antipsychotics in schizophrenia.

PMID- 10884900
TI  - Psychopharmacology of olanzapine. A review.
AB  - Olanzapine is a new atypical antipsychotic (Weaver, 1997). Both early development
      and clinical studies support its safe use. Clinical trials suggest that it is
      efficacious in treating positive symptoms in schizophrenia, and more efficacious
      for negative symptoms and depressive symptoms than traditional antipsychotics. In
      addition, the side-effect profile of olanzapine is favourable, with a low
      incidence of EPS and little increase in prolactin during acute-phase trials. At
      present, olanzapine appears broadly as good as the other novel atypical drugs. As
      a group, the atypical antipsychotics have been recommended for use as first-line
      therapy, in acute schizophrenic relapse, and for those who are responsive, but
      intolerant, to classical antipsychotic medication (Kerwin, 1994; Lieberman,
      1996). The role of olanzapine in treating treatment-resistant patients is
      unproven, and data is awaited comparing olanzapine directly with clozapine. The
      current era of development of drugs for schizophrenia holds great promise, and it
      is the duty of all doctors to make patients aware of the benefits and risks of
      available treatments, and to enable them to choose.

PMID- 10884901
TI  - An investigation into the effectiveness of an early intervention method for
      delayed language development in young children.
AB  - Delayed language development is common and has serious sequelae into adulthood in
      terms of educational, social and emotional development. The objective of this
      study was to test the hypothesis that a group of language-delayed infants
      detected in the first year of life by the screen developed in the author's
      previous study, and receiving intervention at that stage, would not show language
      impairment at the age at which children are usually referred for speech and
      language therapy, whereas an untreated control group would do so. A sample (n =
      122), of very young language-delayed children was divided into matched
      experimental and control groups. The mean (range) age of the sample was 10.6 (8
      21) months. The experimental group received intervention, and both groups were
      followed up until they were 3 years of age to determine whether there were
      differences in language development at that stage. The results showed that at 3
      years, 85% of controls showed language delay while only 5% of the experimental
      group did so. The differences in mean language quotient in experimental and
      control groups were statistically significant (t = 2.701, p < 0.01). At this
      stage, 30% of the controls had been referred for speech and language therapy,
      while none of the experimental group had so been. The intervention was found to
      take relatively little resource and the low dropout rate and high take-up
      indicated that it was popular with carers.

PMID- 10884902
TI  - Drawing together: evaluation of a therapy programme for severe aphasia.
AB  - This paper reports a therapy study that aims to promote communicative drawing in
      a group of seven people with severe and long-standing aphasia. Therapy was
      conducted on individual and group bases over 12 weeks and entailed a range of
      techniques which are described in some detail. Treatment was evaluated using a
      novel generative drawing assessment in which subjects were required to draw
      absent items in response to photographic and conversational cues. Pre- and post
      therapy assessments of untreated skills, such as comprehension, naming and
      gesture, were also conducted. The results indicated that, as a group, the
      subjects' drawing improved. Unchanged performance on the other assessments
      indicated that the gains were specific to the content of therapy and could not be
      attributed to spontaneous recovery. Pre- and post-therapy interviews with carers
      (i.e. relatives and close friends of the individuals) suggested that the effects
      of therapy were also being felt in the home. These results have important
      implications for therapy with people with severe aphasia.

PMID- 10884903
TI  - Group training in communication skills for carers of adults with aphasia.
AB  - This study describes a communication skills group programme for four carers of
      adults with aphasia that ran once a week for 6 consecutive weeks. The content of
      the group was based on an approach previously not described in the literature in
      any detail. Conversation analysis (CA) was used to guide individualized advice
      that was incorporated into the group by the use of written advice sheets.
      Intervention was motivated by the results of a newly developed assessment tool-
      the Conversation Analysis Profile for People with Aphasia (CAPPA)--and a
      quantitative and qualitative analysis of collaborative repair. The CAPPA utilizes
      the methodology of conversation analysis (CA) as a means of both characterizing
      and comparing the relationship between the carers' perception of the aphasia and
      what is occurring in natural conversation. During the group, accurate perceptions
      and strategies that minimized the disruption to the conversation were reinforced,
      while inaccurate perceptions and strategies that appeared to impede interaction
      were discouraged. The use of the CAPPA results and a quantitative/qualitative
      analysis of repair management to measure change pre- and post-group was explored.
      The post-intervention analyses examined three questions in particular: (1) did
      the carers demonstrate more accurate perceptions of their relatives' aphasia?;
      (2) did the carers report a decrease in the problem severity of the aphasia?; and
      (3) was there a change in the time taken to repair a trouble source and was this
      attributable to a change in the management of repair by the carer? The study was
      essentially an investigation of whether this type of approach was beneficial to
      the carers involved. The results suggested that focusing on individualized advice
      and targeting conversation management in the group setting was a useful way of
      providing advice to carers. Furthermore, the CAPPA and a quantitative/qualitative
      analysis of repair management seem to have the potential for motivating the
      individualized advice and measuring the effectiveness of an intervention.

PMID- 10884904
TI  - Phonological awareness skills of 4-year-old British children: an assessment and
      developmental data.
AB  - This study reports developmental data for the phonological awareness and
      processing skills of 57 normally developing Tyneside preschool children, aged
      between 46 and 58 months. The children were assessed on eight tasks: consistency
      of word production, phonological variability according to speech production task,
      non-word imitation, syllable segmentation, rhyme awareness, alliteration
      awareness, phoneme isolation and phoneme segmentation. The results indicated that
      girls and boys performed similarly; socio-economic status significantly affected
      performance on six of the tasks; and age was significantly correlated with
      performance on tasks targeting alliteration, non-word imitation, phonological
      variability, and phoneme isolation and segmentation. The older children were more
      phonologically aware than the younger children.

PMID- 10884905
TI  - Non-word repetition in children with language impairment--pitfalls and
      possibilities.
AB  - Specific language impairment has, although not without controversy, been
      considered as a consequence of a phonological memory deficit. Non-word repetition
      has been proposed as a reliable index of phonological memory and also as
      predictive of lexical and grammatical development in normally developing and
      language-impaired children. The main aim was to study the relationship between
      repetition of words and non-words and expressive language skills (phonology and
      grammar) in 27 5-year-old children with language impairment. The authors also
      wanted to explore the influence of lexical stress on repetition skills. The
      results showed that words were significantly easier to repeat than non-words and
      that non-word repetition skills were significantly correlated to phonological and
      grammatical development. The most important predictor of non-word repetition
      skills was output phonology. The conclusion is that non-word repetition is not a
      single, reliable index of phonological memory in preschool children with language
      impairment. Also, the influence of prosodic variables on segmental aspects of
      speech production should not be overlooked in non-word construction, since it was
      found that unstressed syllables were omitted six times more often in prestressed
      than in post-stressed positions of the words and non-words.

PMID- 10884906
TI  - Characteristics of children attending language units in England: a national study
      of 7-year-olds.
AB  - The present investigation examined the characteristics of 7-year-old children
      attending language units in England. The study involved 242 participants who
      represented a randomized sample of all 7-year-old children spending 50% of more
      of the school week in a language unit. Results are discussed in terms of the
      following questions: what is the non-verbal ability of children attending
      language units?; do children attending language units fit the discrepancy
      criteria between verbal and non-verbal ability diagnostic of specific language
      impairment (SLI)?; and what types of language difficulties do children with SLI
      attending language units have?

PMID- 10884907
TI  - Relevance theory and pragmatic impairment.
AB  - This paper summarizes aspects of relevance theory that are useful for exploring
      impairment of pragmatic comprehension in children. It explores data from three
      children with pragmatic language difficulties within this framework. Relevance
      theory is seen to provide a means of explaining why, in a given context, a
      particular utterance is problematic. It thus enables one to move on from mere
      description of problematic behaviours towards their explanation. The theory
      provides a clearer delineation between the explicit and the implicit, and hence
      between semantics and pragmatics. This enables one to place certain difficulties
      more firmly within semantics and others within pragmatics. Relevance, and its
      maximization in communication, are squarely placed within human cognition, which
      suggests a close connection between pragmatic and cognitive (dis)functioning.
      Relevance theory thus emerges as a powerful tool in the exploration and
      understanding of pragmatic language difficulties in children and offers
      therapeutically valuable insight into the nature of interactions involving
      individuals with such impairments.

PMID- 10884908
TI  - Mother-child interaction revisited: communication with non-speaking physically
      disabled children.
AB  - This paper presents an in-depth analysis of the interaction between mothers and
      their severely physically disabled children who have motor speech disorders. The
      study was designed to partially replicate previous investigations, most notably
      those undertaken by Light et al., to examine if the patterns of conversation
      previously described were observed in interaction involving children of a wide
      age range. Twenty children who had four-limb cerebral palsy, with no diagnosed
      learning difficulties or sensory impairments, and who were between 2 and 10 years
      of age inclusive participated in the research with their mothers. Children's
      speech was unintelligible to their parents out of context and most had been
      provided with aided communication systems. Other carers were excluded from the
      research due to possible differences in interaction style. Conversation between
      mothers and children was videotaped in a standard play situation. The toys used
      to stimulate interaction had been shown to elicit the full range of communication
      skills targeted in the present study from non-disabled children. Videotaped
      interaction was coded to show the structure of conversation and the functions
      used. The mode of communication used by the children was also recorded. In
      addition, communicative functions were elicited from the children in a semi
      scripted conversation with a clinician developed from that used by Light et al.
      Structural moves and communicative functions used by mothers and children were
      examined using mean proportions. Sequential analysis of mother-child interaction
      was also undertaken at both levels to investigate the patterns that recurred in
      conversation. Results support those obtained in previous studies, showing
      restricted conversation patterns and high levels of maternal directiveness.
      Mothers initiated most communicative exchanges, asking many questions and issuing
      many requests for attention, objects or activities. Children across the age range
      produced more response moves than any other move type. Their responses contained
      yes/no answers and acknowledgements, and to a lesser extent provisions of
      information. When children did produce communicative functions other than simple
      confirmation, denials and acknowledgements, they were often not fully understood
      and were followed by requests for clarification by the mothers. Children produced
      a wider range of communicative functions in the semi-scripted elicitation
      conversation with the clinician than in conversation with their mothers (z =
      3.52, p = 0.0002). The results obtained support those of previous research and
      suggest that interaction for children with severe motor and speech impairments
      becomes 'fossilized', changing little throughout childhood. Findings support the
      two-pronged approach to intervention for children using augmentative
      communication systems that is now developing. Intervention should focus not only
      on the children, teaching them how to use their augmentative systems and to
      produce a full range of conversation skills, but also should focus on their
      carers. Training for carers aims to increase their interaction skills, teaching
      them how to facilitate and expand children's communication skills.

PMID- 10884909
TI  - Therapy outcome measures in speech and language therapy: comparing performance
      between different providers.
AB  - BACKGROUND: The use of outcome measures to monitor improved quality of care has
      been advocated for 20 years but has only achieved prominence with the increasing
      resource pressures and related changed in health service provision in the past 6
      years. OBJECTIVE: This paper describes the development of an approach to outcome
      measurement suitable for all patients receiving speech and language therapy. The
      measure, which is based on rating the dimensions of impairment, disability,
      handicap and well-being, is tested to assess whether it can usefully be used to
      compare the services of different providers. METHOD: Five trusts volunteered for
      the study. Service descriptions suggest that these services are typical for the
      purposes of providing speech and language therapy. Twenty-five therapists were
      trained to use the Therapy Outcome Measure (TOM); their reliability was assessed
      and they provided prospective data on clients with speech and language
      impairments related to dysphasia, stammering and dysphonia. RESULTS: The study
      provides evidence indicating the differences in the types of patients being
      referred to different providers of speech and language therapy. Different
      services have different impacts on the number and type of domains and that
      services discharge patients at different points in their recovery. DISCUSSION:
      Different outcomes by different providers may be associated with different
      referral policies, base populations, skills and work policies of therapists.
      Differences in outcomes associated with certain therapy services can initiate the
      task of analysing attributions and progress endeavours to provide equitable
      quality of care which is the philosophy underpinning the move towards
      benchmarking in health service delivery.

PMID- 10884910
TI  - Barriers to collaboration: an analysis of systemic barriers to collaboration
      between teachers and speech and language therapists.
AB  - A systems approach is used to examine the barriers to collaboration found in the
      working practices of speech and language therapists and teachers. Functional,
      structural and systems-environment barriers are found, but few process barriers,
      which may explain why good collaborative practice can be found in the field. The
      differences that serve as barriers are listed and discussed, with a view to
      fostering mutual understanding between teachers and speech and language
      therapists.

PMID- 10884911
TI  - Re: Ward, S., 1999, an investigation into the effectiveness of an early
      intervention method for delayed language development in young children.
      International Journal for Language & Communication Disorder, 34, 243-246.

PMID- 10884912
TI  - Re: Ward, S., 1999 an investigation into the effectiveness of an early
      intervention method for delayed language development in young children.
      International Journal of Language & Communication Disorder, 34,243-246.

PMID- 10884913
TI  - Re: Ward, S., 1999 an investigation into the effectiveness of an early
      intervention method for the delayed language development in young children.
      International Journal of Language & Communication Disorder, 34, 243-264.

PMID- 10884914
TI  - Demystified.... Transcription.
AB  - The transcription of genes could be defined as the intricate molecular manoeuvres
      occurring in the nuclei of cells, which allow the translation of genetic
      information held in the DNA into the proteins required for life. Gene
      transcription is the dominant control point in the production of any protein, and
      is initiated and regulated through the combined activities of a highly
      specialised set of nuclear proteins. This review examines the role of these
      protein "transcription factors" in the production of messenger RNA, the
      information intermediary produced in the nucleus, and transferred to the
      cytoplasm to serve as a template for protein synthesis. In combination with RNA
      polymerase, an extraordinary and complex enzyme required to synthesise new RNA
      molecules, a multitude of transcription factors combine their activities to
      orchestrate and control this elegant process.

PMID- 10884915
TI  - x ray crystallography.
AB  - x Ray crystallography is currently the most favoured technique for structure
      determination of proteins and biological macromolecules. Increasingly, those
      interested in all branches of the biological sciences require structural
      information to shed light on previously unanswered questions. Furthermore, the
      availability of a protein structure can provide a more detailed focus for future
      research. The extension of the technique to systems such as viruses, immune
      complexes, and protein-nucleic acid complexes serves only to widen the appeal of
      crystallography. Structure based drug design, site directed mutagenesis,
      elucidation of enzyme mechanisms, and specificity of protein-ligand interactions
      are just a few of the areas in which x ray crystallography has provided
      clarification.

PMID- 10884916
TI  - Relation of Bcl-2 expression to androgen receptor, p21WAF1/CIP1, and cyclin D1
      status in prostate cancer.
AB  - BACKGROUND: There is currently no effective treatment for recurrent hormone
      refractory carcinomas of the prostate gland. An understanding of the underlying
      mechanisms responsible for the progression of these lesions is likely to be
      important for the development of new therapeutic approaches. Recently, it has
      been suggested that the transition to a hormone independent state is accompanied
      by increased proliferation and bcl-2 gene expression, as well as by a decreased
      apoptotic state. AIM: To investigate the possible role of Bcl-2 and other cell
      cycle regulating proteins in the development of prostatic tumours. METHODS:
      Immunohistochemistry was used to study the relation between the expression of Bcl
      2 and the androgen receptor, as well as p21WAF1/CIP1 (p21), and cyclin D1 status,
      in a series of 89 prostate cancer samples taken before androgen withdrawal
      treatment. RESULTS: Androgen receptor negative tumours expressed significantly
      higher amounts of Bcl-2 than those prostate carcinomas with low/medium androgen
      receptor values. However, in tumours expressing the highest amounts of androgen
      receptor, Bcl-2 expression was also high. A significant positive relation between
      Bcl-2 and p21 expression, as well as an inverse relation between Bcl-2 and cyclin
      D1 expression, was noted. Androgen receptor positive samples also expressed
      significantly higher amounts of cyclin D1. CONCLUSIONS: These results suggest
      that p21 and cyclin D1 expression in prostatic cancer might be modulated by Bcl-2
      and by androgens and in turn this could be relevant to the progression of
      prostatic cancer.

PMID- 10884917
TI  - Amplification of PCR products in excess of 600 base pairs using DNA extracted
      from decalcified, paraffin wax embedded bone marrow trephine biopsies.
AB  - AIMS: To establish a robust method of extracting DNA from paraffin wax embedded
      bone marrow trephine (PBMT) biopsies for the amplification of relatively long
      polymerase chain reaction (PCR) products. METHOD: Xylene and ethanol were used to
      remove paraffin wax from eight formalin fixed, EDTA decalcified PBMT biopsies and
      DNA extraction was performed using a Qiagen QIAamp tissue kit. The DNA samples
      were amplified using nine different PCR primers sets, including those used to
      detect chromosomal translocations (t(11;14) and t(14;18), and clonal B cell
      populations. A t(11;14) PCR product of approximately 600 base pairs (bp) was
      sequenced using dye terminator cycle sequencing. RESULTS: All eight DNA samples
      extracted from PBMT biopsies were amplified successfully to generate DNA
      fragments up to 643 bp in length. Chromosomal translocations and immunoglobulin
      gene rearrangements were detected by PCR in some of the samples. Sequencing of
      the t(11;14) PCR product demonstrated the presence of chimaeric sequences, which
      included both bcl-1 and immunoglobulin heavy chain (IgH) gene sequences,
      consistent with the presence of this translocation. CONCLUSIONS: This method
      enables PCR analyses of PBMT biopsies that were not previously possible, offering
      the prospect of improved accuracy of diagnosis and the monitoring of patients
      with bone marrow disease.

PMID- 10884918
TI  - p53 and K-ras gene mutations in carcinoma of the rectum among Finnish women.
AB  - AIMS/BACKGROUND: The aim of this study was to identify p53 and K-ras gene
      mutations in carcinoma of the rectum among Finnish women. Mutation patterns might
      give clues to aetiological factors when comparisons are made with other human
      tumours. METHODS: Of 134 women with carcinoma of the rectum, paraffin wax
      embedded specimens of the tumour tissue were obtained from 118 patients. Genomic
      DNA was extracted, and exons 4-8 of the p53 gene and codons 12/13 and 61 of the K
      ras gene were amplified, and analysed for mutations by single strand conformation
      polymorphism and direct sequencing. The production of p53 and K-ras proteins was
      studied by immunohistochemistry. RESULTS: The overall crude frequency for
      mutations in the p53 gene was 35% but the true frequency appears to be higher (up
      to 56%). In the K-ras gene, the mutation frequency (15%) was significantly lower
      than that reported for colon cancer. In the p53 gene, the mutation frequency
      increased significantly with patient age. In a high proportion of patients (14%)
      the rectal tumours contained small subclones of tumour cells that displayed
      extremely rare mutations at codons 110 and 232 of the p53 gene. Hot spot codon
      175 mutations were significantly less common in rectal cancer than in cancer of
      the colon. CONCLUSIONS: Rectal cancer among Finnish women has characteristics in
      the mutations of the p53 and K-ras genes that are uncommon in other human
      tumours, including cancer of the colon. A biological explanation of these
      findings is not clear at present, but might be associated with an unidentified
      genetic factor in Finland.

PMID- 10884919
TI  - Expression of an LDL receptor allele with two different mutations (E256K and
      I402T).
AB  - AIMS: To investigate the disease causing event in patients with familial
      hypercholesterolaemia, carrying two mutations each, E256K in exon 6 and I402T in
      exon 9, of the gene encoding the low density lipoprotein (LDL) receptor. It was
      not known whether the mutations were positioned in cis or trans, or if they were
      each pathogenic separately or only when present together. METHODS: Polymerase
      chain reaction, denaturing gradient gel electrophoresis and sequencing were used
      to characterise the LDL receptor locus of the patients and family members. The
      different LDL receptor mutants, constructed in vitro by oligonucleotide directed
      mutagenesis, were expressed in LDL receptor deficient Chinese hamster ovary
      (CHO1d1A7) cells, to determine the effects of the mutations on LDL receptor
      function. RESULTS: The two mutations were located on the same allele of the LDL
      receptor gene. All mutant constructs resulted in the production of a detectable
      protein in CHO cells. The cells expressing only the I402T mutation, or the
      combination of I402T and E256K mutations, were seriously affected in mediating
      uptake and degradation of LDL. Contrary to initial predictions, the cells
      expressing only the E256K mutation showed essentially the same binding, uptake,
      and degradation of 125I labelled LDL as cells transfected with normal LDL
      receptor cDNA. These results suggest that the pathogenic mutation in the patients
      heterozygous for the E256K/I402T allele is the I402T mutation, and that E256K
      alone is a rare sequence variation, which does not affect LDL receptor protein
      function. E256K was not detected either in DNA from a healthy population or in
      DNA from other hypercholesterolaemic patients studied. CONCLUSIONS: Despite the
      information available on the structure-function relations between the LDL
      receptor and LDL receptor like proteins, predictions about the disease causing
      potential of a mutation are not reliable. These results suggest that the I402T
      mutation is pathogenic and that the substitution of E256K alone is a rare
      sequence variation, without a detectable phenotype modulating effect.

PMID- 10884920
TI  - Epstein-Barr virus (EBV) in infectious mononucleosis: detection of the virus in
      tonsillar B lymphocytes but not in desquamated oropharyngeal epithelial cells.
AB  - AIMS: Despite its well established tropism for B cells, the nature of the
      cellular compartment(s) mediating primary and persistent Epstein-Barr virus (EBV)
      infection is still a matter of controversy. In view of the association of EBV
      with several lymphoid and epithelial malignancies, resolution of this issue is
      important. METHODS: Desquamated oropharyngeal epithelial cells from 10 patients
      with acute infectious mononucleosis and from seven chronic virus carriers were
      studied for evidence of EBV infection using in situ hybridisation for the
      detection of the small EBV encoded RNAs (EBERs) and of the viral genome. In
      addition, immunocytochemistry was used to detect the BZLF1 transactivator protein
      of EBV. RESULTS: There was no evidence of latent or replicative EBV infection in
      oropharyngeal epithelial cells in any of the samples. In contrast, EBV infected B
      cells were readily identified in a tonsil from a patient with infectious
      mononucleosis. CONCLUSIONS: The results suggest that oropharyngeal epithelial
      cells are not a major site of EBV infection and provide further support for the
      notion that B cells mediate primary and persistent EBV infection.

PMID- 10884921
TI  - Localisation of HHV-8 in AIDS related lymphadenopathy.
AB  - BACKGROUND: Many lymph node abnormalities have been described in AIDS. These
      include opportunistic infections that sometimes result in spindle cell
      pseudotumours, Kaposi's sarcoma (KS), malignant lymphoma (Hodgkin's and non
      Hodgkin's), and florid reactive hyperplasia. Among these, reactive hyperplasia is
      the most common manifestation of AIDS related lymphadenopathy. AIM: To examine
      whether human herpesvirus 8 (HHV-8), the aetiological agent of KS, can be
      localised in AIDS related lymphadenopathy and whether its appearance in such
      nodes is predictive of Kaposi's sarcoma development. METHODS: A series of human
      immunodeficiency virus (HIV) positive men (n = 21) with AIDS related
      lymphadenopathy who at the time of presentation had KS or subsequently developed
      KS (n = 5) were examined. The prevalence of HHV-8 was assessed in these patients
      using solution phase polymerase chain reaction (PCR), real time TaqMan
      quantitative PCR, and in cell amplification techniques (PCR in situ hybridisation
      (PCR-ISH) and labelled primer driven in cell amplification). RESULTS: Using
      standard solution phase PCR in a nested format, only two of the 21 patients with
      AIDS related lymphadenopathy were positive for HHV-8. The lymph node of one of
      these patients contained KS lesions. Three HHV-8 positive patients were
      identified using TaqMan PCR (the original two positive patients and one
      additional patient). All of the positive patients either subsequently developed
      KS (n = 2) or had KS at the time of diagnosis (n = 1). Two additional patients
      subsequently developed KS, but were negative for HHV-8 by solution phase PCR and
      TaqMan PCR. Using PCR-ISH, HHV-8 amplicons were identified in some lymphoid cells
      (in one patient) and in spindle cells of the KS lesion in another. The positive
      lymphoid cells were predominantly concentrated in B cell areas of the affected
      lymph nodes, confirming the B cell tropism exhibited by HHV-8. CONCLUSIONS: The
      presence of HHV-8 in AIDS related lymphadenopathy is predictive of KS development
      and probably represents seeding of HHV-8 infected B cells from the peripheral
      blood. These findings support a role for HHV-8 in the pathobiology of KS.

PMID- 10884922
TI  - Improved in situ detection method for telomeric tandem repeats in metaphase
      spreads and interphase nuclei.
AB  - Peptide nucleic acid technology (PNA) has become an extremely useful tool and
      promises to impact on molecular biology and diagnostics. These synthetic DNA
      analogues pair with DNA and RNA molecules according to Watson and Crick base
      pairing rules. This paper describes a sensitive and quick fluorescent in situ
      hybridisation (ISH) technique to determine DNA telomere repeat sequences (TTA
      GGG)n using epifluorescence microscopy. Telomeres are special, repeated
      structures at the end of each eukaryotic chromosome and serve as protective caps
      to prevent DNA rearrangements and fusion of chromosomes. A model system has been
      developed, using stimulated peripheral blood lymphocytes, which facilitates
      simultaneous detection of telomeres in metaphase as well as in interphase nuclei.
      A fluorescein isothiocyanate labelled PNA probe (18 mer) directed against
      complementary telomeric sequences at the end of each chromosome is used. In
      addition, a simple, easy to perform PNA-ISH protocol is described that overcomes
      common hybridisation problems encountered using DNA and RNA oligoprobes.
      Furthermore, the usefulness of a chromogenic immunocytochemical detection system
      is shown for PNA-ISH.

PMID- 10884924
TI  - A new editor for Ophthalmic and Physiological Optics

PMID- 10884923
TI  - Direct multiplex amplification of DNA from a formalin fixed, paraffin wax
      embedded tissue section.
AB  - The extraction of DNA from formalin fixed, paraffin wax embedded tissue can be
      problematical, with long protocols producing low yields. This report describes a
      very simple and useful method for amplifying DNA from formalin fixed, paraffin
      wax embedded tissue without the need for prior DNA extraction. This method allows
      direct polymerase chain reaction (PCR) based molecular analysis of fixed tissue.
      It is an invaluable method if clinical biopsy specimens are to be investigated,
      because extraction of uncontaminated DNA from such small samples can be very
      difficult or even impossible. It will also facilitate the study of intratumour
      heterogeneity, with the analysis of multiple small areas from within a single
      tumour section. In addition, this method can be used for other samples where only
      a few tests are to be carried out and a stock of DNA is not required, thus
      shortening the analysis time.

PMID- 10884925
TI  - Communicating scientific findings to the wider community

PMID- 10884926
TI  - Accommodation microfluctuations and pupil size during sustained viewing of visual
      display terminals.
AB  - Accommodation microfluctuations comprise two dominant frequencies; a low
      frequency component (LFC < or = 0.6 Hz) and a high frequency component (1.0 Hz <
      HFC < 2.1 Hz). In the present experiment we examine accommodation
      microfluctuations and steady-state pupil responses during sustained viewing of
      visual display terminals (VDTs). Steady-state accommodation and pupil responses
      were measured continuously and simultaneously using a modified Canon Autoref R-1
      infra-red objective optometer and an Hamamatsu C3160 Perceptscope Video Area
      Analyser. Measurements were obtained at three time intervals (0, 10 and 20 min)
      during a 20 min reading task presented on five different displays. With the
      displays placed at 50 cm, the task was to locate and identify typographical
      errors in one of five sets of standard text. Five young visually-normal
      emmetropic subjects with a mean age of 22.5 +/- 3.0 years participated in the
      study. Two-way ANOVA revealed no significant variation in the magnitude of the
      accommodation microfluctuations with either display or task duration, nor was
      there any significant interaction between these two factors. There was no
      significant variation in mean pupil diameter with either display or task
      duration. These measures may have the potential to provide objective information
      about visual display quality.

PMID- 10884927
TI  - Astigmatism.
AB  - The quantitative representation and analysis of astigmatism present difficulties
      for the researcher. The case is made that the difficulties arise because of the
      way astigmatism is conceived and defined. In most cases astigmatism is regarded
      as cylinder. Cylinder, however, is not invariant under spherocylindrical
      transposition and, hence, cannot strictly be regarded as meaningful. The purpose
      of the paper is to find a rational, context-free, invariant and universally
      applicable definition of astigmatism for all quantitative analyses. One is led to
      definitions of astigmatism and its components some of which have already appeared
      in the literature but which are not in use in analyses of astigmatism.
      Astigmatism is defined with respect to pure sphere. In the case of thin systems
      (including keratometric measurements and refraction) astigmatism turns out to be
      Jacksonian power, that is, the power of a Jackson crossed cylinder. The power of
      every thin system can be regarded as consisting of two orthogonal components,
      sphere and astigmatism. The astigmatism of thin systems itself further decomposes
      naturally into two orthogonal components called ortho- and oblique astigmatism.
      In the case of thick systems, like the eye itself, astigmatism decomposes
      naturally into three orthogonal components, ortho-, oblique and antisymmetric
      astigmatism. The approach is based on the general definition of power in paraxial
      optics, the dioptric power matrix, and leads to useful graphical representations.
      Because of its mathematical foundation the analysis can claim completeness and
      contextual independence. Furthermore it is also directly applicable to the four
      fundamental paraxial properties of optical systems.

PMID- 10884928
TI  - New approximation for the whole profile of the human crystalline lens.
AB  - This paper presents a new approximation for the whole profile of the human
      crystalline lens by the use of only one analytical function for both
      unaccommodated lens and the lens on accommodation. Approximation of the anterior
      and posterior lens profile is composed of hyperbolic cosine functions and is
      given in polar coordinates. Each of the hyperbolic cosines is modulated by the
      function of hyperbolic tangent type. The curvature of the hyperbolic cosine in
      polar coordinates is discussed and some results concerning the stability of its
      central radius of curvature are shown. Fitting of the hyperbolic cosine type
      curve to various results of the lens curvature measurements is presented.
      Examples of profiles of the lens under accommodation are given. It is shown that
      this approximation can be used for the description of iso-indical profiles inside
      the lens.

PMID- 10884929
TI  - Response of the human visual system to variable illuminant conditions: an
      analysis of opponent-colour mechanisms in colour constancy.
AB  - Illuminant changes in a scene generally cause displacements in the chromaticity
      and luminance of the objects of which the scene is composed; however, the visual
      system is capable of maintaining a constant object colour appearance
      independently of the illuminant. This is the phenomenon traditionally known as
      colour constancy. A classical asymmetric colour-matching experiment is reported
      to address two aspects of colour constancy: successive colour constancy and the
      role of opponent mechanisms in it. To this end, colour matches are made with
      chromatically complex backgrounds under different illuminants and with an equal
      energy light source as standard. The results are analysed in the cone-excitation
      space, separately along the L-2M and S dimensions. Data are presented showing
      that colour-vision mechanisms respond differently to illuminant changes when
      colour constancy is considered at both receptoral and post-receptoral levels. The
      L- and M-cones tend to adapt so as to support colour constancy, whereas S-cones
      are strongly influenced by the illuminant changes. In addition, the data suggest
      good approaches to colour constancy linked particularly to the yellow-blue
      mechanism.

PMID- 10884930
TI  - Kinematics of eye movement.
AB  - In a simplified fashion, the motion of the eyeball in its orbit consists of
      rotations around a fixed point. Therefore, this motion can be described in terms
      of Euler's angles of rigid body dynamics. However, there is a physiological
      constraint in the motion of the eye which reduces to two its degrees of freedom,
      so that one of Euler's angles is not an independent variable. This paper reviews
      the basic features of the kinematics of the eye and the laws governing its
      motion.

PMID- 10884931
TI  - Glaucoma in optometric practice: a survey of optometrists.
AB  - AIMS/BACKGROUND: With the ageing population, numbers of glaucoma patients are an
      increasing problem in ophthalmic outpatient clinics. A postal questionnaire
      survey was carried out in Northern Ireland with the aim of finding out how well
      placed optometrists are to become involved in the monitoring of glaucoma.
      RESULTS: Of the 171 practices surveyed, 68% of the senior practitioners
      responded. One practice was without a tonometer and one practice was without
      visual field instrumentation. Age criteria were used by 95% of practitioners for
      measuring intraocular pressure (IOP) and 82% used appropriate selection criteria
      for visual field testing. An IOP of 25 or 26 mmHg was used by 45% of
      practitioners as the level for referral if there are no risk factors; 89% would
      refer at any level if a visual field defect and disc cupping were present.
      CONCLUSION: The results confirm that the majority of optometrists are well
      equipped for the screening of glaucoma. However a significant investment in
      training and equipment would be required if any sort of shared care scheme were
      to be introduced.

PMID- 10884932
TI  - Evaluation of the pinhole pupillometer.

PMID- 10884933
TI  - Lipids and barrier function of the skin.
AB  - The purpose of the present manuscript is to review the chemical and physical
      properties of epidermal lipids and to relate these properties to the formation
      and function of the permeability barrier of the skin. Lipids accumulate in small
      organelles known as lamellar granules as epidermal keratinocytes differentiate.
      This lipid is extruded into the intercellular spaces where it undergoes enzymatic
      processing to produce a lipid mixture consisting of ceramides, cholesterol and
      fatty acids. This intercellular lipid is uniquely organized into a multilamellar
      complex that fills most of the intercellular space of the stratum corneum. The
      barrier properties of the stratum corneum are related to the phase behavior of
      the intercellular lipids. It has been proposed that a structurally unusual
      acylglucosylceramide is thought to be involved in assembly of the lamellar
      granules, and a related acylceramide may have a major influence on the
      organization of the lamellae in the stratum corneum.

PMID- 10884934
TI  - Hypothesis: the epidermal permeability barrier is a porous medium.
AB  - The stratum corneum is a complex biological material characterized by very low
      permeability to water and most other molecules. This material may be thought of
      as a 'porous medium' composed of impermeable and permeable regions. Intercellular
      lipid membranes in the stratum corneum are postulated to exist in a mixture of
      two phases: solid (i.e. impermeable) and liquid crystalline (permeable). The
      corneocyte envelope is classified as impermeable. Diffusion mechanisms of solutes
      within, across and between the intercellular lamellae are discussed. This model
      represents a refinement of previous theories about the physical structures
      responsible for the low observed permeability of the stratum corneum.

PMID- 10884935
TI  - Insights into the molecular organization of lipids in the skin barrier from
      infrared spectroscopy studies of stratum corneum lipid models.
AB  - In order to gain some insight into the molecular organization of lipids in the
      skin barrier we used Fourier transform infrared (FTIR) spectroscopy to
      investigate models of the stratum corneum (SC) containing deuterated hexadecanoic
      acid, cholesterol, and ceramide 2 or ceramide 5. In both models there is clear
      evidence of separate conformationally ordered domains of ceramide and fatty
      acids. In addition, these chains are packed in orthorhombic subcells at
      physiological temperatures. The ceramide headgroup behavior indicates distinct
      hydrogen bonding patterns between the ceramide 2 and ceramide 5 models. In the
      ceramide 2 model the amide I mode is split into two components suggesting strong
      transverse intermolecular hydrogen bonding between headgroups. In contrast, no
      amide splitting is observed for ceramide 5 although the amide frequencies are
      indicative of strong hydrogen bonding. These observations on the molecular
      organization of SC lipids are discussed in terms of skin barrier function.

PMID- 10884936
TI  - The lipid organisation in the skin barrier.
AB  - The main function of the skin is to protect the body against exogenous
      substances. The skin barrier is located in the outermost layer of the skin, the
      stratum corneum. This layer consists of keratin enriched cells embedded in lipid
      lamellae. These lamellae form the main barrier for diffusion of substances
      through the skin. In diseased skin the barrier function is often impaired. For a
      full understanding of the properties of the human skin barrier, insight in the
      stratum corneum lipid organisation is of great importance. In this paper a short
      description of the lipid organisation in normal human stratum corneum will be
      given, after which the role the main lipid classes play in the stratum corneum
      lipid organisation will be described. In addition the effect of cholesterol
      sulfate and calcium on the lipid organisation will be discussed. Finally a new
      model, the "sandwich model", will be proposed that describe the localisation of
      the fluid phases in the stratum corneum.

PMID- 10884937
TI  - The skin barrier from a lipid perspective.
AB  - This contribution summarises the results from a number of investigations
      undertaken in the spirit of the Domain Mosaic Model proposed by Forslind in 1994.
      Atomic Force Microscopy (AFM) studies on the two-dimensional phase behaviour of
      some stratum corneum lipids revealed phase separation of the lipids in the
      typical case and the ability of cholesterol to reduce the line tension between
      phases. A theoretical model was developed describing the response of an oriented
      stack of polar lipid bilayers in the presence of a gradient in water chemical
      potential (water solution to humid air). The gradient gives rise to an
      inhomogeneous water swelling, and presumably to a liquid crystal-to-gel
      transition in the lamellar region closest to humid air. Skin penetration
      enhancers such as Azone and oleic acid cause phase transformations in lipid
      bilayer systems which may be relevant in the context of skin permeation.

PMID- 10884938
TI  - Visualization of percutaneous 3H-estradiol and 3H-norethindrone acetate transport
      across human epidermis as a function of time.
AB  - Developing transdermal therapeutic systems for estradiol and norethindrone
      acetate raised questions about the steroids penetration pathway across and
      retention in the skin. This paper describes the distribution of 3H-estradiol and
      3H-norethindrone acetate in human stratum corneum after topical application to
      dermatomed skin in vitro. The study involved (a) permeation experiments to
      determine the steroid flux, (b) autoradiographical visualization of the steroid
      distribution in the same skin samples, and (c) a correlation between flux and
      skin distribution in time. On correlating the steroid flux with intraepidermal
      steroid distribution, it was concluded that both permeants were bound in the skin
      tissue. The steroids were preferentially located in or close to the intercellular
      lipids of the stratum corneum, indicating that both transport and binding
      occurred via this domain of the stratum corneum. This study demonstrated the
      importance of correlating drug flux with intraepidermal drug distribution as a
      function of time.

PMID- 10884939
TI  - Desquamation in the stratum corneum.
AB  - To maintain a constant thickness of the stratum corneum the desquamation rate and
      the de novo production of corneocytes is delicately balanced. Using a plantar
      stratum corneum model we have obtained evidence that proteolysis is a central
      event in the desquamation process. A number of regulatory mechanisms for
      desquamation have been postulated based on our findings.

PMID- 10884940
TI  - The skin barrier: analysis of physiologically important elements and trace
      elements.
AB  - Changes in the properties of the skin barrier should have correlates in the
      physiological status of the differentiating epidermal cells. However, the
      quantitative distributions of physiologically important elements and trace
      elements of the skin has been a neglected area of research for lack of tools to
      investigate this highly differentiated tissue. With the event of the particle
      probes, the electron microprobe and the scanning proton microprobe, it has become
      possible to investigate different aspects of normal skin physiology as well as
      pathophysiological processes. In addition penetration profiles of allergenic
      metals can be demonstrated with the trace element sensitive proton probe. Future
      approaches to the study of skin physiology in normal and pathological conditions
      should incorporate other techniques including immunological and biochemical
      tagging of particular cells to achieve a broad basis for interpretations of data.

PMID- 10884941
TI  - Basal cell carcinoma--new aspects of diagnosis and treatment.
AB  - The incidence of basal cell carcinoma is increasing. New aspects of diagnosis and
      treatment are discussed in this thesis. Interferon can be used for the treatment
      of BCC. In paper I, 15 patients received 13.5 x 10(6) IU of alfa-2b-interferon
      intralesionally. Four patients healed completely whereas a 75% reduction was seen
      in 5 cases. Intralesional alfa-2b-interferon can reduce the number of excisions
      during Mohs Micrographic Surgery. Topical photodynamic therapy involves the
      application of ALA on the skin. In tumour cells selectively, formation of the
      photosensitizer Pp IX occurs. After 4 hours of occlusion of ALA the area is
      irradiated with light at a wavelength of 630 nm. Tumour cells are selectively
      destroyed during this procedure. 144/157 SBCC healed in this series and 14/18 Mb
      Bowen (paper II). The method is only suited for thin BCCs as the result on
      thicker lesions is poor (2/10 healed). The cosmetic result was generally good or
      excellent. Another way of utilising the tumour selectivity of Pp IX is for
      diagnostic purposes. Instead of illuminating with 630 nm, 365, 366 and 405 nm are
      used to induce a specific fluorescence. In the present paper (III), 50% of facial
      BCCs with ill-defined borders could be completely visualised and another 23%
      partly outlined. The technique did not seem to work in 27% of the cases. The
      critical factor using ALA is probably the relatively poor penetrance through the
      skin. In paper IV, microdialysis is used for pharmacokinetic studies of ALA for
      the first time. The concentration of ALA increases rapidly in lesional skin
      whereas there is virtually no penetration in healthy skin. Also, the blood
      perfusion in BCCs was investigated by means of laser Doppler Perfusion Imager.
      The perfusion in skin overlying a BCC was 2.5 fold higher compared to normal
      skin. For BCCs with ill-defined borders Mohs Micrographic Surgery is generally
      recommended. Regarding Mohs Micrographic Surgery, Sweden is underserved as only
      1% of BCCs are treated with Mohs Micrographic Surgery as opposed to 30% in the
      US. Consequently, the Swedish cases are probably more severe. The long-term
      results are reported in paper V. Two hundred and twenty-eight tumours were
      followed for at least 5 years. The rate of recurrence was 8%. This figure is
      slightly higher than in international materials but surprisingly low considering
      the type of tumours.

PMID- 10884942
TI  - Causes and effects of the chronic inflammation in venous leg ulcers.
AB  - The pathogenesis of venous leg ulcers is multifactorial. In this review article
      new physiological, molecular and cellular abnormalities in venous ulcers related
      to the chronic inflammation are presented and discussed. Venous hypertension
      causes disturbed microcirculation and pathological changes of the capillaries,
      which eventually locks the condition in a self-amplifying, detrimental cascade
      with persistent elevated levels and activities of pro-inflammatory cytokines and
      proteases preventing progress into a healing phase. As a consequence fibroblasts
      senescence and become less responsive to growth factors the older the ulcers
      become. Current data imply there is no deficiency but rather an unfavorable
      distribution of growth factors in venous ulcers. An imbalance in proteolytic
      enzymes and their endogenous inhibitors is a common finding in chronic venous leg
      ulcers. Variation in disease severity and concomitant ailments in this
      heterogeneous patient group may explain the contradictory results in the
      literature. Thus, to advance the areas of research further, longitudinal studies
      involving larger number of patients are required to identify the major pathogenic
      factors.

PMID- 10884943
TI  - Public health genetics: an emerging interdisciplinary field for the post-genomic
      era.
AB  - Public health genetics is an exciting interdisciplinary area that brings all the
      public health sciences to bear on the emerging challenge of interpreting the
      medical and public health significance of genetic variation within populations.
      Sequencing of the human genome will generate an avalanche of genetic information
      to be linked with information about microbial, chemical, and physical exposures;
      nutrition, metabolism, lifestyle behaviors, and medications. The public health
      genetics mini-symposium in this volume includes articles dealing with educational
      innovations, host-pathogen interactions in infectious diseases, nutrition/genetic
      interactions in cancers, and population screening for hemochromatosis. Additional
      topics addressed here are ecogenetics and risk assessment, the genetics of
      unhealthful behaviors, and ethical and policy issues. Finally, a set of
      principles for community-based health research in populations is presented as a
      public health-oriented counterpart to the principle of autonomy and the practice
      of informed consent that have become key elements of ethics in medical care and
      medical research with individuals.

PMID- 10884944
TI  - Host-pathogen interactions in emerging and re-emerging infectious diseases: a
      genomic perspective of tuberculosis, malaria, human immunodeficiency virus
      infection, hepatitis B, and cholera.
AB  - On exposure to a pathogen, a host may resist infection, become subclinically
      infected, or progress through several stages from mild to severe infection.
      Chronic sequelae may or may not occur. Host factors, particularly host genes,
      influence many of these stages. We have used a model of the continuum of
      pathogenesis of infectious diseases to consider the effect of host genes on five
      pathogens of significant public health burden: Mycobacterium tuberculosis,
      Plasmodium species, human immunodeficiency virus, hepatitis B virus, and Vibrio
      cholerae. The relationships between these infections and polymorphisms in human
      leukocyte antigen, cytokines, other immune response, or pathogen receptor genes
      are reviewed. We discuss gene-gene interactions and their effects in complex
      settings, such as coinfections with several pathogens. Priorities for prevention
      and control of these pathogens include vaccines and antimicrobial drugs. Research
      on how host genes can influence vaccine responses and the efficacy of drugs or
      other interventions, as well as further research into the relationship of host
      genes to infectious disease outcomes, may lead to new strategies for prevention
      and control.

PMID- 10884945
TI  - Nutrition, genetics, and risks of cancer.
AB  - Dietary patterns, nutrients, and other constituents of food are major components
      of the environmental influences that contribute to risk for cancer, and the study
      of interactions between nutritional and genetic factors is a new and important
      area or research. This review describes the concepts and principles underlying
      this area of study and types of relationships between nutritional and genetic
      factors, and it provides examples of specific diet-gene interactions that are of
      current interest, with an emphasis on implications for cancer prevention and
      public health. Polymorphisms exist in the genes for the activating and
      conjugating metabolizing enzymes, and the induction of metabolizing enzyme
      activity by nutritional factors may result in either the activation of a
      carcinogen or the detoxification of a reactive intermediate metabolite. The
      relationship between the methylenetetrahydrofolate reductase gene and dietary
      folate is an example of a diet-gene interaction that involves a polymorphism in a
      vitamin metabolism gene, and the presence of the variant appears to influence
      both risk for cancer and folate requirements. Diet-gene interactions likely
      contribute considerably to the observed inter-individual variations in cancer
      risk in response to exposures to the nutritional factors that have the potential
      to promote or protect against cancer. Insights into mechanisms by which
      nutritional factors affect the process of carcinogenesis are provided by
      knowledge of the targeted gene function and enzyme activity. Increased knowledge
      in this area will allow a more refined approach to reducing risk for cancer, with
      diet interventions targeted toward individuals and subgroups that are genetically
      susceptible and responsive to the effects of nutritional factors.

PMID- 10884946
TI  - Population screening in hereditary hemochromatosis.
AB  - Hemochromatosis is a common autosomal recessive condition found in the homozygous
      state in 1/200-1/400 people of northern-, central-, and western-European origin.
      It causes increased iron storage, which may lead to liver cirrhosis, liver
      cancer, heart disease, arthritis, and diabetes in many but not all affected
      adults, with a higher frequency in males. The condition is easily treated by
      repeated venesections without side effects but is frequently overlooked.
      Population screening of adults using iron indices alone or combined with DNA
      testing has therefore been recommended, but a consensus conference in 1997
      recommended that such screening be deferred, owing to uncertainty regarding the
      extent of clinical disease that may develop in individuals detected by such
      programs. There was also concern that DNA screening results might be used for
      discrimination in insurance and occupational settings. Screening family members
      of patients with evidence of definite iron loading, however, is accepted by all
      observers. Because serious complications may be overlooked, a more aggressive
      stance toward case detection in the adult population has been advocated by some
      observers, realizing that unnecessary treatment might occur. Because additional
      information regarding the spectrum of clinical disease in homozygotes in now
      accumulating, a consensus conference in the near future is suggested to consider
      appropriate policies.

PMID- 10884947
TI  - The interface of genetics and public health: research and educational challenges.
AB  - As the target date for the sequencing of the human genome approaches, there is
      growing recognition that public health practice, research, and education will be
      impacted by new genetic technologies and information and that a multidisciplinary
      approach is required. Research in the emerging field of public health genetics
      encompasses a broad range of disciplines and will increasingly involve the
      interactions among the investigators in these fields. An overview of these areas
      of research is provided, with illustrative examples. Education in public health
      genetics needs to address a variety of audiences, including public health
      graduate students and practitioners, students from related disciplines, and
      health care professionals. Two new graduate programs at the Universities of
      Michigan and Washington and training opportunities for public health
      professionals are described. These educational efforts must be ongoing so that
      the potential of genetic technology and information can be appropriately used to
      benefit the health of all.

PMID- 10884948
TI  - Looking back on "causal thinking in the health sciences".
AB  - It has now been over a quarter of a century since the publication of Mervyn
      Susser's Causal Thinking in the Health Sciences (1973, Oxford University Press),
      the first book-length treatment of causal reasoning and inference in our field.
      Major contributions of this work were its holistic focus on the origins of health
      outcomes in the context of ecologic systems and its invigoration of the
      literature on causal criteria in epidemiology. Although a recent resurgence of
      interest in social context has revivified many points made by Susser, a formal
      basis for causal analysis consistent with this ecologic perspective has failed to
      emerge in public health research. Susser's discussion of causal criteria, on the
      other hand, helped spur a vigorous dialogue that has persisted unabated to the
      present day. Although the basic outline of the criteria has evolved little, their
      applications, interrelations, and relative contributions to causal judgments have
      been the subject of continued and sometimes contentious debate.

PMID- 10884949
TI  - Causal effects in clinical and epidemiological studies via potential outcomes:
      concepts and analytical approaches.
AB  - A central problem in public health studies is how to make inferences about the
      causal effects of treatments or agents. In this article we review an approach to
      making such inferences via potential outcomes. In this approach, the causal
      effect is defined as a comparison of results from two or more alternative
      treatments, with only one of the results actually observed. We discuss the
      application of this approach to a number of data collection designs and
      associated problems commonly encountered in clinical research and epidemiology.
      Topics considered include the fundamental role of the assignment mechanism, in
      particular the importance of randomization as an unconfounded method of
      assignment; randomization-based and model-based methods of statistical inference
      for causal effects; methods for handling noncompliance and missing data; and
      methods for limiting bias in the analysis of observational data, including
      propensity score matching and sensitivity analysis.

PMID- 10884950
TI  - Building bridges between populations and samples in epidemiological studies.
AB  - The increased use of rigorous population-sampling methods and the analysis of
      data from those samples in cross-sectional surveys, case-control studies,
      longitudinal-cohort investigations, and other epidemiological research efforts
      have raised important statistical issues for health analysts. We describe the
      origin, implications, and some plausible resolutions for several of these issues.
      Some of the main issues we consider include (a) establishing whom the sample
      represents; (b) using sample weights; (c) understanding the role of other
      important features, such as the use of sampling stratification and the selection
      of clustered groups of population members; and (d) finding ways to analyze study
      data with key sampling features in mind. Ultimately, resolution of all of these
      issues requires that analysts clearly define a reference population and then
      understand the role of design features in relating sample results to that
      population.

PMID- 10884951
TI  - Multilevel analysis in public health research.
AB  - Over the past few years there has been growing interest in considering factors
      defined at multiple levels in public health research. Multilevel analysis has
      emerged as one analytical strategy that may partly address this need, by allowing
      the simultaneous examination of group-level and individual-level factors. This
      paper reviews the rationale for using multilevel analysis in public health
      research, summarizes the statistical methodology, and highlights some of the
      research questions that have been addressed using these methods. The advantages
      and disadvantages of multilevel analysis compared with standard methods are
      reviewed. The use of multilevel analysis raises theoretical and methodological
      issues related to the theoretical model being tested, the conceptual distinction
      between group- and individual-level variables, the ability to differentiate
      "independent" effects, the reciprocal relationships between factors at different
      levels, and the increased complexity that these models imply. The potentialities
      and limitations of multilevel analysis, within the broader context of
      understanding the role of factors defined at multiple levels in shaping health
      outcomes, are discussed.

PMID- 10884952
TI  - Should we use a case-crossover design?
AB  - The first decade of experience with case-crossover studies has shown that the
      design applies best if the exposure is intermittent, the effect on risk is
      immediate and transient, and the outcome is abrupt. However, this design has been
      used to study single changes in exposure level, gradual effects on risk, and
      outcomes with insidious onsets. To estimate relative risk, the exposure frequency
      during a window just before outcome onset is compared with exposure frequencies
      during control times rather than in control persons. One or more control times
      are supplied by each of the cases themselves, to control for confounding by
      constant characteristics and self-confounding between the trigger's acute and
      chronic effects. This review of published case-crossover studies is designed to
      help the reader prepare a better research proposal by understanding triggers and
      deterrents, target person times, alternative study bases, crossover cohorts,
      induction times, effect and hazard periods, exposure windows, the exposure
      opportunity fallacy, a general likelihood formula, and control crossover
      analysis.

PMID- 10884953
TI  - Water reclamation and unrestricted nonpotable reuse: a new tool in urban water
      management.
AB  - Growing urbanization accompanying growing population is increasing the demand for
      water supply in communities throughout the world. Water resources for many cities
      are already proving inadequate. Additional water resources are inherently more
      costly and are often not available because other communities and/or land owners
      have the water rights. Although conservation, particularly through demand
      management, may delay the need for additional sources for a short period, the
      need is inevitable. One approach that has been found to provide substantial
      additional water for communities is the reclamation of wastewaters produced by
      the communities themselves for unrestricted nonpotable purposes, such as for
      landscape and market crop irrigation, industry, cooling towers, air conditioning,
      toilet flushing, construction, vehicle washing, and environmental enhancement.
      This is done by providing dual distribution systems. Nonpotable reuse is already
      widely practiced despite the fact that the reclaimed water distribution systems
      needed to be installed in existing communities. Inasmuch as additional water is
      needed for growing populations, the costs would be substantially reduced if the
      two systems were to be built at the same time in the newly developing areas.
      Reuse of reclaimed water for potable purposes may be feasible, but it imposes
      added public health risks that need to be accepted only as a last resort.

PMID- 10884954
TI  - Epidemiology and prevention of injuries among adolescent workers in the United
      States.
AB  - In the United States, most adolescents are employed at some time during their
      teen years. Provisions of the Fair Labor Standards Act, the nation's child labor
      law, address some of the risks of adolescent employment; however, > 70 teenage
      workers are estimated to die from work-related injuries each year, with greater
      risk among males, whites, and older adolescents. Furthermore, the nonfatal work
      related injuries of the > or = 64,000 teens who receive emergency department care
      each year are believed to significantly undercount actual injuries. Many of these
      nonfatal injuries are severe, with 15%-45% leading to work restriction or
      permanent disabilities. Significant methodological issues limit the ability of
      existing surveillance systems to monitor youth worker injury. Risk factor and
      intervention research is very limited, but does suggest the role of some worker
      characteristics, management practices, and training issues. However, these
      factors need more careful study. This review considers existing information about
      occupational injuries among adolescents and identifies needs for research and
      policy attention.

PMID- 10884955
TI  - The effects of changing weather on public health.
AB  - Many diseases are influenced by weather conditions or display strong seasonality,
      suggestive of a possible climatic contribution. Projections of future climate
      change have, therefore, compelled health scientists to re-examine weather/disease
      relationships. There are three projected physical consequences of climate change:
      temperature rise, sea level rise, and extremes in the hydrologic cycle. This
      century, the Earth has warmed by about 0.5 degrees centigrade, and the mid-range
      estimates of future temperature change and sea level rise are 2.0 degrees
      centigrade and 49 centimeters, respectively, by the year 2100. Extreme weather
      variability associated with climate change may especially add an important new
      stress to developing nations that are already vulnerable as a result of
      environmental degradation, resource depletion, overpopulation, or location (e.g.
      low-lying coastal deltas). The regional impacts of climate change will vary
      widely depending on existing population vulnerability. Health outcomes of climate
      change can be grouped into those of: (a) direct physical consequences, e.g. heat
      mortality or drowning; (b) physical/chemical sequelae, e.g. atmospheric transport
      and formation of air pollutants; (c) physical/biological consequences, e.g.
      response of vector- and waterborne diseases, and food production; and (d)
      sociodemographic impacts, e.g. climate or environmentally induced migration or
      population dislocation. Better understanding of the linkages between climate
      variability as a determinant of disease will be important, among other key
      factors, in constructing predictive models to guide public health prevention.

PMID- 10884956
TI  - Toxicological bases for the setting of health-related air pollution standards.
AB  - The development of air pollution standards ideally involves the integration of
      data from the disciplines of epidemiology, controlled clinical studies, and
      animal toxicology. Epidemiological studies show statistical associations between
      health outcomes and exposure; they cannot establish a definite cause-effect
      relationship. The utility of toxicological studies is to establish this
      relationship. Recently, there was simultaneous promulgation of a new National
      Ambient Air Quality Standard (NAAQS) for particulate matter < 2.5 microns in
      aerodynamic diameter (PM2.5) and a revised NAAQS for ozone (O3). The O3 NAAQS was
      based, in part, on a sound foundation of toxicological data from controlled
      exposure studies in humans and animals. It also relied on epidemiological studies
      of hospital admissions for respiratory diseases. Such studies also served as
      important bases for the new PM2.5 NAAQS. However, the most influential bases for
      the PM NAAQS were the numerous and generally consistent epidemiological studies
      that associated exposure with premature mortality in susceptible subpopulations
      and the inability of numerous hypothesized confounding factors to negate the
      associations. Using ozone and PM as examples, this paper discusses the scientific
      basis for NAAQS promulgations in situations in which the underlying database
      differed greatly in the extent of toxicological support.

PMID- 10884957
TI  - Religion and health: public health research and practice.
AB  - Research examining the relationships between religion and the health of
      individuals and populations has become increasingly visible in the social,
      behavioral, and health sciences. Systematic programs of research investigate
      religious phenomena within the context of coherent theoretical and conceptual
      frameworks that describe the causes and consequences of religious involvement for
      health outcomes. Recent research has validated the multidimensional aspects of
      religious involvement and investigated how religious factors operate through
      various biobehavioral and psychosocial constructs to affect health status through
      proposed mechanisms that link religion and health. Methodological and analytical
      advances in the field permit the development of more complex models of religion's
      effects, in keeping with proposed theoretical explanations. Investigations of
      religion and health have ethical and practical implications that should be
      addressed by the lay public, health professionals, the research community, and
      the clergy. Future research directions point to promising new areas of
      investigation that could bridge the constructs of religion and health.

PMID- 10884958
TI  - A review of collaborative partnerships as a strategy for improving community
      health.
AB  - Collaborative partnerships (people and organizations from multiple sectors
      working together in common purpose) are a prominent strategy for community health
      improvement. This review examines evidence about the effects of collaborative
      partnerships on (a) community and systems change (environmental changes), (b)
      community-wide behavior change, and (c) more distant population-level health
      outcomes. We also consider the conditions and factors that may determine whether
      collaborative partnerships are effective. The review concludes with specific
      recommendations designed to enhance research and practice and to set conditions
      for promoting community health.

PMID- 10884959
TI  - Oral health in the United States: the post-fluoride generation.
AB  - Tremendous strides have been made in reducing the incidence of tooth decay,
      periodontal diseases, and associated loss of teeth in adults and children since
      the inception of community water fluoridation programs. Yet the disadvantaged and
      poor have not fully shared in the benefits. Other challenges to oral health
      remain. Oral cancer and related smoking and smokeless tobacco use remain major
      public health problems. Access to preventive and therapeutic dental care is far
      from universal. Public health programs similar in commitment to the approach of
      community water fluoridation programs initiated in the 1950s and 1960s are needed
      to address neglected oral health needs of underserved and high-risk populations
      in the United States.

PMID- 10884960
TI  - The new public health litigation.
AB  - In recent years there has been an increasing use of litigation as a public health
      tool. Litigation has been brought to advance policies concerning such matters as
      tobacco, gun violence, and lead paint. This article discusses this development
      and the criticism that can be leveled at using litigation to develop public
      health policy. The article concludes that, although litigation may not always be
      successful, it can deter dangerous activities and play an important role in
      advancing the political and social struggle for public health.

PMID- 10884961
TI  - Baby and the brain: advances in child development.
AB  - As child morbidity and mortality declined during the twentieth century, a
      corresponding increase occurred in the relevance of child psychological well
      being to public health. Evidence of this trend is the proliferation of programs
      intended to ameliorate conditions that place children in jeopardy of poor
      developmental outcome. Most recently, neurobiologic information on brain function
      and structure has been used to promote strategies for optimizing child
      development. This review will evaluate the current state of knowledge relating
      early child development to brain research and illustrate the potential misuse of
      this information. It will also suggest the following: (a) the extrapolation of
      neuroscience results to early academic and social enrichment programs obscures
      the magnitude of potential effects of these programs relative to the vast burden
      of risk imposed by poverty, and (b) an emphasis on intellectual functioning
      misses the most compelling evidence on the role of the early social environment
      in mediating establishment of neural networks that regulate a child's response to
      stress and capacity for self-control.

PMID- 10884962
TI  - Health promotion in the city: a review of current practice and future prospects
      in the United States.
AB  - To achieve its health goals, the United States must reduce the disproportionate
      burden of illness and poor health borne by urban populations. In the 20th
      century, patterns of immigration and migration, changes in the global economy,
      increases in income inequality, and more federal support for suburbanization have
      made it increasingly difficult for cities to protect the health of all residents.
      In the last 25 years, epidemics of human immunodeficiency virus infections and
      substance abuse and increases in homelessness, lack of health insurance, rates of
      violence, and concentrations of certain pollutants have also damaged the health
      of urban residents. Several common strategies for health promotion are described,
      and their relevance to the unique characteristics of urban populations is
      assessed. To identify ways to strengthen health promotion practices in U.S.
      cities, lessons have been taken from five related fields of endeavor: human
      rights, church- and faith-based social action, community economic development,
      youth development, and the new social movements. By integrating lessons from
      these areas into their practice, public health professionals can help to
      revitalize the historic mission of public health, contribute to creating
      healthier cities, and better achieve national health objectives.

PMID- 10884963
TI  - The rise and decline of homicide--and why.
AB  - A dramatic rise in homicide in the latter half of the 1980s peaked during the
      1990s and then declined at an equally dramatic rate. Such trends in homicide
      rates can be understood only by examining rates in specific age, sex, and racial
      groups. The increase primarily involved young males, especially black males,
      occurred first in the big cities, and was related to the sudden appearance of
      crack cocaine in the drug markets of the big cities around 1985. This development
      led to an increased need for and use of guns and was accompanied by a general
      diffusion of guns into the larger community. The decline in homicide since the
      early 1990s has been caused by changes in the drug markets, police response to
      gun carrying by young males, especially those under 18 years old, the economic
      expansion, and efforts to decrease general access to guns, as well as an increase
      in the prison population and a continued decline in homicide among those over age
      24. The lessons learned from the recent homicide trends and the factors
      associated with them have important implications for public health and the
      criminal justice system.

PMID- 10884964
TI  - Income inequality and health: what does the literature tell us?
AB  - This paper reviews the large and growing body of literature on the apparently
      negative effects of income inequality on population health. Various hypotheses
      are identified and described that explain the empirically observed association
      between measures of income inequality and population health. We have concluded
      that data from aggregate-level studies of the effect of income inequality on
      health, i.e. studies at the population and community (e.g. state) levels, are
      largely insufficient to discriminate between competing hypotheses. Only
      individual-level studies have the potential to discriminate between most of the
      advanced hypotheses. The relevant individual-level studies to date, all on U.S.
      population data, provide strong support for the "absolute-income hypothesis," no
      support for the "relative-income hypothesis," and little or no support for the
      "income-inequality hypothesis." Results that provide some support for the income
      inequality hypothesis suggest that income inequality at the state level affects
      mainly the health of the poor. There is only indirect evidence for the
      "deprivation hypothesis," and no evidence supports the "relative-position
      hypothesis." Overall, the absolute-income hypothesis, although > 20 years old, is
      still the most likely to explain the frequently observed strong association
      between population health and income inequality levels.

PMID- 10884965
TI  - Evaluating the State Children's Health Insurance Program: critical
      considerations.
AB  - The Balanced Budget Act of August 1997 was intended to improve the insurance
      coverage of low-income children. Although no specific mandates for evaluation
      accompanied the legislation, states are expected to assess its impact. Insurance
      improves access to and use of health services. The extent to which this is
      associated with better health depends on the kinds of services received. Access
      to a regular source of care is a critical characteristic. If this source of care
      provides good primary care, a variety of benefits would be expected to accrue.
      Thus, evaluation of the benefits of the State Children's Health Insurance Program
      should address not only improved coverage by health insurance for eligible
      children, but also the extent to which children receive high-quality primary
      care, including appropriate referrals when needed. Maternal access to and use of
      services is also a critical factor. Targets for evaluation include state
      activities to (a) enroll through outreach, inform through education, and develop
      information systems for tracking; (b) assess the degree of penetration of
      insurance among low-income children and their mothers, the availability of health
      care personnel, and the adequacy of benefits conferred by the insurance, primary
      care services, and back-up specialty services; and (c) obtain evidence of
      improved health status. This article details approaches that can appropriately be
      used to address each of these aspects of concern.

PMID- 10884966
TI  - Preference-based measures in economic evaluation in health care.
AB  - Estimating preferences for states of health has been an active area of research
      in recent years. Unlike psychophysical approaches, which discriminate levels of
      health status, preference-based approaches incorporate values or utilities for
      health outcomes and can be used in cost-effectiveness analyses to aid resource
      allocation decisions. This chapter considers issues and controversies involved in
      using preference-based measures in economic evaluation in health care, with a
      particular emphasis on cost-utility analysis and the estimation of quality
      adjusted life years. Topics considered include techniques for measuring
      preferences, the use of preference-based classification systems, the relationship
      between patient and community preferences, methods for obtaining utilities from
      clinical trials, mapping health status from health utilities, the development of
      "off-the-shelf" preference weights, and proposed alternatives to quality-adjusted
      life years. We also consider applications of cost-utility analyses to public
      health interventions. Although cost-utility analyses have become more popular
      recently, many challenges remain for the field. Widespread acceptance of the
      methodology likely awaits more consensus on measurement techniques, as well as
      educational efforts in the public health and medical communities on the
      usefulness of the approach.

PMID- 10884967
TI  - Telemedicine: a new health care delivery system.
AB  - The resurgence of telemedicine can be attributed to its potential for addressing
      intransigent problems in health care, including limited accessibility, cost
      inflation, and uneven quality. After discussing definitions and the genesis of
      telemedicine, this review focuses on conceptual issues and an assessment of past
      research. The scope and methodological rigor necessary for sustained development
      and policy making have been limited in this area of research, owing to the nature
      of extant telemedicine projects and the lack of a comprehensive research strategy
      that specifies the objectives of telemedicine research regarding accessibility,
      cost, and quality. Research strategies and a framework for analysis are
      discussed. Without a commitment to the types of research objectives, framework,
      and strategy presented here, the considerable promise of telemedicine, as an
      innovative system of care, may not be fully realized.

PMID- 10884968
TI  - The changing nature of rural health care.
AB  - The rural health care system has changed dramatically over the past decade
      because of a general transformation of health care financing, the introduction of
      new technologies, and the clustering of health services into systems and
      networks. Despite these changes, resources for rural health systems remain
      relatively insufficient. Many rural communities continue to experience shortages
      of physicians, and the proportion of rural hospitals under financial stress is
      much greater than that of urban hospitals. The health care conditions of selected
      rural areas compare unfavorably with the rest of the nation. The market and
      governmental policies have attempted to address some of these disparities by
      encouraging network development and telemedicine and by changing the rules for
      Medicare payments to providers. The public health infrastructure in rural America
      is not well understood but is potentially the most fragile aspect of the rural
      health care continuum.

PMID- 10884969
TI  - Assessment in long-term care.
AB  - Long-term care has begun to rely heavily on assessment as a basis for determining
      eligibility and payment for services, as well as for planning needed care.
      Mandated assessments have been introduced into nursing homes and will soon be
      required for home health care and rehabilitation. Many states use a formal
      structured assessment process to establish clients' eligibility for institutional
      or community-based care. The common feature of such assessment is attention to
      physical functioning, but other domains are also relevant, including affect,
      social function, cognition, pain and discomfort, and satisfaction. Taken
      together, this cluster is often referred to as quality of life. While some
      measures attempt to infer this information from clients' behavior, it is best
      obtained directly from clients' responses whenever possible. The other major
      component of a long term care assessment relates to obtaining information on
      clients' preferences and values. These data are important both for weighting the
      individual components of an assessment and for directly addressing preferences
      about the care and lifestyle available.

PMID- 10884970
TI  - [Roles of general medicine faculties in undergraduate medical education].
AB  - Education is most important in the roles of general medicine faculties. It is
      desirable that family physicians occupy a half of the total physicians, in order
      that the people lead healthy life. The educational subject of the general
      medicine is the training of a family physician. It includes following three
      areas: (1) basic clinical competence, (2) community-based primary care, and (3)
      general medicine for inpatients services. In Hokkaido University Hospital, we are
      mainly doing the outpatient clinic. Many of the patients need a state of
      psychosocial approach. University hospitals are not suited for the study of
      primary care, although it is suited for the education of basic clinical
      competence. For that students need to practice it in the clinic of the community
      rather than university hospitals. Faculty development is important to the reform
      of medical education. Many of medical schools of the whole country have come to
      hold the workshop of faculty development. Hokkaido University School of Medicine
      carried out it 3 times. The Japanese Academy of Primary Care is holding a
      workshop every year. It is requested that the university faculties cooperate with
      the primary care physicians in the community for improving medical education.

PMID- 10884971
TI  - [Roles of thymic epithelial cells in generation of NK-T cells from aly/aly
      mouse].
AB  - NK1.1+ TCR alpha/beta+ (NK-T) cells are markedly reduced in the alymphoplasia
      mutant mouse. We have previously shown that the defect resides in the thymic
      environment where the NK-T precursors develop but not in the precursor cells
      themselves. In the present study to elucidate the recipient factor(s) that is
      responsible for the development of NK-T cells, radiation bone-marrow chimeras
      were established by using alymphoplasia mutant mice as a donor strain and either
      beta 2 microglobulin knock-out (beta 2m-/-) or CD1d1-/- mice as recipients, both
      of which lack CD1 molecules. It was shown that substantial numbers of NK-T cells
      with typical surface phenotypes were generated both in the thymus and the spleen
      of the chimeras. The NK-T cells produced equivalent or slightly elevated levels
      of IL-4 and IFN-gamma in response to an immobilized anti-CD3 monoclonal antibody.
      These findings suggested that expression of beta 2m-associated ligands, namely
      CD1 molecules, on the thymic epithelium was not necessarily an essential
      requisite for the NK-T cell development. Furthermore, we demonstrate herein that
      the intrathymic transfer of a medullary thymic epithelial cell line of normal
      mouse can rescue the generation of the NK-T cells in the thymus of alymphoplasia
      mouse. These results demonstrate that function(s) represented by certain types of
      thymic epithelial cells is indispensable for development of NK-T cells.

PMID- 10884972
TI  - [Diabetic nephropathy and low molecular weight advanced glycation end-product in
      urine].
AB  - Glucose reacts non-enzymatically with amino groups of proteins to produce diverse
      groups of protein-bound moieties with cross-linking properties called advanced
      glycation end-products (AGEs). A large number of studies suggest that tissue and
      circulating AGEs, especially those bound to small peptides, play an important
      role in the pathogenesis and development of diabetic complications. The aim of
      the present study was to evaluate AGE-peptide levels in the urine in various
      stages of diabetic nephropathy and to analyze structures of AGEs generated in
      vivo. Urine samples were obtained from 100 type-2 diabetic patients with various
      stages of nephropathy, 39 non-diabetic patients with renal dysfunction, and 20
      control subjects with neither diabetes nor renal disease. Low molecular weight
      peptides (< 10 kDa) isolated from each sample were used. With the use of size
      exclusion HPLC monitored by AGE-specific fluorescence, three main fluorescence
      peaks were detected at molecular weights of 6,000 Da, 2,500 Da, and 300 Da. The
      fluorescence intensity of total AGE-peptide and 6,000 Da peak AGE-peptide is
      enhanced together with the development of renal dysfunction in diabetic patients,
      which strongly correlated with the level of serum creatinine. There was no
      difference in total urinary AGE between diabetic and non-diabetic hemodialysis
      patients, suggesting that insufficient clearance during dialysis is more
      important than AGE production. A competitive ELISA using a polyclonal anti-AGE
      antibody, anion-exchange HPLC, and reversed-phase HPLC were performed on the
      peaks appearing in size-exclusive HPLC to further characterize the AGE
      composition. The 300 Da product was specific to diabetic patients with chronic
      renal failure and hemodialysis patients, which may be a good marker to
      distinguish diabetic from non-diabetic renal failures. We also speculated that
      because of its low molecular weight, the 300 Da product might represent the final
      degradation product of AGE-peptides in the kidney.

PMID- 10884973
TI  - Effects of tacrolimus hydrate (FK-506) on the expression of tissue factor in THP
      1 human monocyte cell line.
AB  - Accelerated coronary atherosclerosis in cardiac allografts is a major factor
      limiting survival after heart transplantation, and activation of the coagulation
      system contributes to accelerated transplant atherosclerosis. Accordingly,
      increased tissue factor (TF) expression by monocyte/macrophages may play a
      pivotal role underlying deposition of fibrin in the affected vessels. To evaluate
      the potential effects of an important immunosuppressive agent, tacrolimus hydrate
      (FK-506), on monocyte/macrophages and their response to lipopolysaccharide (LPS),
      we exposed human monocyte/macrophage cell line (THP-1 cells), to LPS and
      characterized its procoagulant activity (PCA). FK-506 exerted a concentration
      dependent inhibitory effect on LPS (10 micrograms/ml) induction of procoagulant
      activity, identified as TF activity as judged from immunostaining of TF antigen
      and by functional characterization with the use of coagulation factor VII
      deficient plasma and an antibody against human TF. In addition, the reverse
      transcription polymerase chain reaction demonstrated reduced expression of TF
      mRNA in LPS-stimulated THP-1 cells exposed to FK-506. Thus, FK-506 acts favorably
      not only as a direct immunomodulating agent but also as an alleviator of local
      activation of the coagulation cascade contributing to transplant arteriopathy
      through modulation of monocyte expression of TF.

PMID- 10884974
TI  - Helicobacter pylori in culture: an ultrastructural study.
AB  - Helicobacter pylori (H. pylori) is generally observed in the gastric mucus and on
      the epithelial cells in human, and is related to gastric disorders. Although many
      morphological studies have been performed on H. pylori, the precise
      ultrastructure of this organism has not been reported upon to the present. In
      this study, H. pylori (ATCC 43504) was cultured in a liquid medium for seven days
      and observed using scanning and transmission electron microscopic methods every
      day. The reproduction of the bacteria in culture was also examined daily, and the
      length and width of the organisms were measured with the use of Micro Computer
      Imaging Device (MCID) System. Spiral forms were dominant over the initial two
      days (the length and width: 2.04 +/- 1.12 microns and 0.49 +/- 0.12 micron on the
      1st day, 1.71 +/- 0.96 microns and 0.38 +/- 0.12 micron on the 2nd day)
      respectively. Coccoid forms (diameter: 0.80 +/- 0.36 micron) were predominant on
      subsequent days. The bacterium had a cell wall membrane (15 nm thick) and a
      cytoplasmic membrane (10 nm thick). A hollow granule (0.15 +/- 0.06 micron in
      diameter) and a dense granule (0.12 +/- 0.04 micron in diameter) were observed in
      a cytoplasm filled with ribosomes. The flagella (51.1 +/- 6.6 nm total in
      diameter) with a sheath (12 nm thick) originated from a concave depression (less
      than 50 nm in depth) at the end of the organism which possessed a knob (less than
      0.1 micron in diameter) at the distal end, which frequently attached to adjacent
      organisms. The coccoid form generally showed precariously membranous and
      intracytoplasmic ultrastructures with few flagella. A few of the coccoid forms
      possessed distinctive cellular ultrastructures with solid flagella similar to
      those found in the spiral forms.

PMID- 10884975
TI  - Functional modification of a murine macrophage cell line, J744A.1, transfected
      with rat csk genes.
AB  - In a previous study of this laboratory, a macrophage cell line, J774A.1,
      transfected with rat csk gene and overexpressing the Csk proteins has been
      established. These Csk transfectants showed depressed productions of monokines
      and nitric oxide (NO), but enhanced production of prostaglandin E2 (PGE2). In the
      present study, mechanism(s) underlying the reciprocal functions seen in NO and
      PGE2 productions was investigated. When aminoguanidine, an inhibitor of NO
      synthesis, was added to the Csk transfectants stimulated with lipopolysaccharide
      (LPS), not only NO production but also PGE2 production was suppressed. Exogenous
      NO showed no influence on PGE2 production by the transfectants stimulated with
      LPS. It was also shown that mitogenactivated protein kinase (MAPK) pathway was
      activated in the Csk transfectants as compared to parental J774A.1 or a vector
      control, J.pBK2, cells. Large amounts of phosphorylated MAPK were detected in the
      Csk transfectants compared to J774A.1. This finding appeared to be consistent
      with the result that MAPK inhibitor completely abolished NO production by J774A.1
      cells upon stimulation with LPS + interferon-gamma (IFN-gamma), whereas the
      inhibitor partially blocked the NO production by J.Csk transfectants which
      expressed large amounts of Csk protein. The overexpressed Csk resulted in
      suppression of phagocytosis of latex beads and uptake of acetyl-low-density
      lipoprotein (LDL) by the transfectants. The present findings demonstrate that Csk
      regulates NO and PGE2 productions independently and suggest that introduction of
      csk gene may be applicable to understanding the pathogenesis of certain diseases
      where dysregulated macrophages are involved.

PMID- 10884976
TI  - [Drug treatment for secondary prevention of myocardial infarction].
AB  - The effects of drug treatment on cardiac events for 11 years from January 1986 to
      December 1996 were investigated in 1,483 patients with myocardial infarction,
      1,164 men and 319 women (mean age 60.1 +/- 11.2 years), followed up for 17.4 +/-
      20.9 months. Seventy-one patients (4.8%, 33 cases per 1,000 person-year) had
      cardiac events (recurrent myocardial infarction, sudden death and death by
      congestive heart failure). Multivariate analysis showed treatment with
      cholesterol lowering agents and beta-blockers reduced cardiac events, whereas
      administration of antiarrhythmic agents increased cardiac events. Univariate
      analysis showed that the incidence of cardiac events was 2.2% in patients treated
      with cholesterol lowering agents but 6.2% in patients without treatment, showing
      a significant difference (p < 0.01). The incidence was 3.2% for patients treated
      with beta-blockers and 6.8% for those without (p < 0.01), showing that beta
      blockers were also effective to reduce cardiac events. Antiplatelet agents were
      also effective (3.7% vs 7.1%, p < 0.01). Calcium antagonists, angiotensin
      converting enzyme inhibitors and warfarin were not effective. Nitrates (6.0% vs
      3.1%, p < 0.01) and antiarrhythmic agents (13.7% vs 3.6%, p < 0.01) increased the
      incidence of cardiac events. A placebo-controlled, double blind, large clinical
      multicenter study is required to confirm these results.

PMID- 10884977
TI  - [Diffuse left ventricular hypokinesis mimicking dilated cardiomyopathy with multi
      vessel coronary vasospasm].
AB  - We investigated 7 patients with multi-vessel coronary vasospasm (> or = 75%) and
      diffuse left ventricular hypokinesis by coronary angiography and
      echocardiography. Four patients were male and 3 were female and mean +/- SD age
      was 63.0 +/- 11.2 years. Chief complaints were dyspnea in 3 patients, and chest
      pain, appetite loss, palpitation and general fatigue in one each. New York Heart
      Association functional classification was I in one patient, II in 5 and III in
      one. Mean heart rate was 73.9 +/- 11.6 beats/min. Initial echocardiography showed
      left ventricular end-diastolic diameter (LVDd) 54.4 +/- 5.5 mm, left ventricular
      end-systolic diameter (LVDs) 43.7 +/- 4.8 mm and percentage fractional shortening
      (%FS) 19.7 +/- 2.6%. The left ventricle was not remarkably enlarged despite poor
      contraction. Coronary vasospasm was induced after acetylcholine injection into
      the right coronary artery in 6 patients, left anterior descending artery in 7 and
      circumflex artery in 5. Four patients developed three-vessel coronary vasospasm.
      Three patients underwent endomyocardial biopsy which showed non-specific mild
      fibrosis. They were treated with nitrates and/or Ca-antagonists to prevent
      coronary vasospasm. Follow-up echocardiography was performed in 6 patients after
      8.5 +/- 6.6 months. Echocardiography revealed marked improvement in left
      ventricular contraction (LVDd 49.7 +/- 4.6 mm, LVDs 35.8 +/- 4.4 mm, p < 0.05;
      %FS 27.9 +/- 4.5%, p < 0.05). These data suggested that left ventricular dilation
      was not prominent despite the poor contractility in patients with multi-vessel
      coronary vasospasm and diffuse left ventricular hypokinesis. The left ventricular
      dysfunction might be hibernating myocardium produced by multiple episodes of
      coronary vasospasm. Anti-vasospastic agents were effective in these patients.

PMID- 10884978
TI  - [Relationship between endothelial function and female hormone level in very old
      females: evaluation from ischemic reactive hyperemic response in forearm
      vessels].
AB  - Recently, the mechanism of longevity in females was proposed to be associated
      with female hormones. This study examined the effect of aging and sex on vascular
      endothelial function, and the relationship between female hormone level and
      endothelial function by ischemic reactive hyperemic response in the forearm using
      plethysmography. The study population consisted of 246 healthy subjects aged from
      20 to 76 years (119 males, 127 females) and 20 healthy females aged 85 years and
      older (85 to 103 years; mean age 94 years) without distinct cardiovascular
      disease, hypertension, diabetes mellitus, renal disease, liver dysfunction or
      anemia. Levels of the female hormones, estradiol and estriol, were measured in
      females aged more than 85 years. The duration of reactive hyperemia decreased
      with aging, but the difference between males and females was not significant at
      any age. In females, the duration was markedly decreased from 110 +/- 36 sec in
      the fifties to 81 +/- 29 sec in the sixties or older (p < 0.05). Excess flow also
      showed similar changes to the duration of reactive hyperemia. The duration of
      reactive hyperemia and excess flow in females aged 85 years and older were
      similar to those in the fifties, but was significantly longer than those in
      females 60 years or older. The concentrations of estradiol (44.9 +/- 27.1 pg/ml)
      and estriol (22.1 +/- 13.4 pg/ml) in females aged 85 years were higher than in
      the sixties. There was a positive correlation between the duration of reactive
      hyperemia and the concentration of estradiol (r = 0.56, p < 0.01) or estriol (r =
      0.57, p < 0.01). In summary, vascular endothelial function was impaired gradually
      with aging, but preservation of the function in healthy, very old females was
      closely associated with levels of female hormone.

PMID- 10884979
TI  - [Surgical treatment for mitral regurgitation: mid-term outcome following mitral
      valve repair].
AB  - Mid-term results of mitral valve repair for mitral regurgitation were evaluated
      in 173 consecutive patients (mean age 53 years, 107 males, 66 females) treated
      from July 1991 to March 1998. Pathological causes of the mitral valve disease
      were degenerative in 118 patients, infective endocarditis in 25, rheumatic in 13,
      and ischemic in 8 (ischemic cardiomyopathy in 7). The principal technique was
      chordal replacement with expanded polytetrafluoroethylene sutures for prolapse of
      the anterior leaflet, and Carpentier's sliding leaflet technique for prolapse of
      the posterior leaflet. Most patients received ring annuloplasty with a rigid ring
      and flexible band (physiological remodeling annuloplasty). Intraoperative
      transesophageal echocardiography was used after 1993. There were 7 operative
      deaths (4%) and 7 mitral valve replacements (4%) during the same operation.
      Successful repair was achieved in 96% of patients with mitral regurgitation. Mean
      follow-up was 35 months (range 2 to 78 months). Survival at 6 years was 85 +/-
      10% of all patients, 98 +/- 2% in degenerative cases. Six patients required
      reoperation (1.2%/patient-year) and mean time interval between initial operation
      and reoperation was 33.1 months. Four patients with atrial fibrillation had
      thromboembolic events (0.8%/patient-year). There were no anticoagulant-related
      complications. Freedom from reoperation and all valve-related event at 6 years
      was 88 +/- 6% and 84 +/- 6%. Late postoperative Doppler echocardiography revealed
      satisfactory results in 93% of the patients. Mitral valve repair using chordal
      replacement, sliding plasty and ring annuloplasty provides excellent mid-term
      results.

PMID- 10884980
TI  - [Intracardiac floating thrombi in patients with acute pulmonary thromboembolism].
AB  - The mortality and morbidity associated with residual intracardiac floating
      thrombi in patients with acute pulmonary thromboembolism remain uncertain.
      Thirteen patients (2 men and 11 women, mean age 56 +/- 15 years) with pulmonary
      thromboembolism underwent echocardiography within 24 hours from onset of
      symptoms. Four patients (31%) had floating intracardiac thrombi in the right
      heart: 3 in the right atrium and one in the inferior vena cava. The time to
      evaluation by echocardiography was shorter than in the patients without thrombi.
      The thrombi disappeared shortly (3.2 +/- 2.4 hr) after thrombolysis without
      adverse effects in these patients. After thrombolysis, clinical symptoms improved
      and pressure gradient between the right ventricle and right atrium decreased
      significantly (p < 0.01) from baseline 47 +/- 6 to 26 +/- 5 mmHg. Major bleeding
      complications occurred in 3 (43%) of the patients who underwent thrombolysis.
      Right-side intracardiac floating thrombus was easily detectable by early
      echocardiography. Thrombolytic agents are likely to be effective in patients with
      intracardiac floating thrombi.

PMID- 10884981
TI  - [Abnormal Q wave in the right precordial leads unmasked during right bundle
      branch block in a patient with anteroseptal myocardial infarction: a case
      report].
AB  - Electrocardiography in a 77-year-old woman showed small R waves in leads V1-V3 3
      hours after the onset of acute anteroseptal myocardial infarction. Abnormal Q
      waves appeared in leads V1-V3 only during intermittent right bundle branch block.
      The normal septal force disappeared after transmural septal infarction and a
      small force of right ventricle origin became apparent as a small R wave in V1.
      Right bundle branch block delayed activation of right ventricle, and thereby
      deleted the initial R wave and unmasked the Q wave of the septal infarction.
      Appearance of a Q wave in leads V1-V3 with right bundle branch block should not
      be assumed to reflect the extension of myocardial infarction.

PMID- 10884982
TI  - [Efficacy of cibenzoline for chest oppression and ventricular arrhythmia during
      effort and alcohol consumption in a patient with hypertrophic obstructive
      cardiomyopathy: a case report].
AB  - A 67-year-old man presented with chest oppression and palpitation during effort
      and alcohol consumption. Echocardiography demonstrated asymmetric septal
      hypertrophy and systolic anterior motion of the anterior mitral leaflet with a
      pressure gradient of 80 mmHg across the left ventricular outflow tract (LVOT),
      leading to the diagnosis of hypertrophic obstructive cardiomyopathy. During the
      treadmill exercise test, blood pressure decreased with electrocardiographic ST
      segment depression and subsequent frequent premature ventricular contractions.
      Holter-electrocardiographic monitoring also showed ST-segment depression with
      premature ventricular contractions during effort and alcohol consumption.
      Coronary angiography showed no abnormalities and cardiac catheterization at
      baseline showed a systolic pressure gradient of only 2 mmHg across the LVOT.
      However, the gradient increased to 33 mmHg after premature ventricular
      contraction, 27 mmHg at Valsalva maneuver and 75 mmHg with dobutamine infusion (5
      micrograms/kg/min) and disappeared with 70 mg of intravenous cibenzoline.
      Medication with cibenzoline (300 mg/day) for one month reduced the LVOT gradient
      at rest to 53 mmHg and strikingly improved symptoms and exercise tolerance and
      also suppressed premature ventricular contractions during exercise and alcohol
      consumption. We conclude that cibenzoline was effective for reduction of LVOT
      gradient both at rest and during exercise and alcohol consumption.

PMID- 10884983
TI  - A 34-year-old man with fever and cardiomegaly.

PMID- 10884984
TI  - [A 51-year-old man with pulmonary aspergillosis].

PMID- 10884985
TI  - [Surgical anatomy of the hepatic hilar area].
AB  - It is important to understand the main variations of the biliary and vascular
      elements inside the plate system for hilar bile duct carcinoma because all
      variations of these elements occur in this plate system. The plate system
      consists of the hilar plate, cystic plate, and umbilical plate which cover the
      extrahepatic vascular system and are fused with the hepatoduodenal ligament. The
      bile duct and vascular system that penetrate the plate system form Glisson's
      capsule in the liver, but the caudate branch and the medial segmental branch are
      exceptions. The bile duct and hepatic artery accompanying the plate system can be
      exfoliated from the portal vein with numerous lymph ducts and nerves. The bile
      ducts in the right hepatic lobe are classified into 4 types, and the standard
      type is present in 53-72% of cases. In the left bile duct, the medial segmental
      bile duct is connected in the vicinity of the hilar area in 35.5% of cases, and
      these cases should be treated the same as the caudate lobe in hilar bile duct
      carcinoma. Generally, there is little main variation of the portal vein (16-26%),
      but more variation in the hepatic artery (31-33%). During surgery for hilar bile
      duct carcinoma, it is important to observe the plate system and the many
      variations of the bile duct and vascular system.

PMID- 10884986
TI  - [Three-dimensional cholangiography and angiography for hilar cholangiocarcinoma].
AB  - Cholangiography is the most fundamental and reliable examination for diagnosis of
      the extent of bile duct carcinoma. Hepatic angiography is also informative for
      diagnosis of vascular invasion. However, an accurate understanding of three
      dimensional biliary and vascular anatomy at the hepatic hilum is not easily
      gained by conventional cholangiography and angiography. We have performed three
      dimensional cholangiography and angiography (3D-CG & AG) using rotational DSA
      (Advantx ACT) and a 3D spinning digital imaging system in 29 patients with hilar
      cholangiocarcinoma, etc. 3D-CG & AD provides clear three-dimensional
      visualization of the biliary tract and blood vessels affected by bile duct
      cancer, and useful information on optimal resection. Of 13 patients with hilar
      cholangiocarcinoma undergoing resection, curative resection was carried out in 11
      (85%). 3D-CG & AG is considered to be an indispensable imaging modality for
      evaluation of the extent and staging of hilar cholangiocarcinoma.

PMID- 10884987
TI  - [Spreading patterns of hilar bile duct cancer].
AB  - Spreading patterns of hilar bile duct cancer were investigated based on cases
      resected in our institution and reported cases in Japan. Forty-seven patients
      underwent resection in our institution during the past 20 years. Three
      patients(12%) survived for more than 5 years. The depth of tumor invasion was m
      or fm in 4 and se or si in 26 patients. Positive cancer invasion in the cut end
      was classified as hm2 or dm2 in 8 patients and em2 in 13. Twenty-four (60%) of 40
      patients investigated histologically had positive lymph node metastases. Invasion
      of the ss layer or deeper perineural invasion occurred in 92.5%. In terms of
      direct invasion of the liver, hinf1 occurred in 20(42.6%). Fourteen(29.8%) han
      invasion of the portal vein(more than vs1). Patients with invasion of the hepatic
      artery were not resected. The 5-year survival rate by cancer stage was 38% in
      stage I, 20% in stage II, 16% in stage III, and 0% in stage IV. Surgery was
      assessed as Cur A in 19 patients (46.3%), Cur B in 7 (17.1%), and Cur C in 15
      (36.6%). In Cur A patients the 5-year survival rate was 18%, while that for our
      Cur B and Cur C patients was 0%. Our patient series was more advanced in terms of
      cancer stage than the statistical Japanese series and both included a significant
      number of noncurative cases. Hepatic resection of the right or left lobe, medial
      segment, and S4a and S5, combined resection of the caudal lobe, and combined
      portal vein resection are important as radical surgery in the treatment of this
      cancer.

PMID- 10884988
TI  - [Preoperative portal embolization for hilar bile duct carcinoma].
AB  - When extensive resection of normally functioning parenchyma such as in extended
      right lobectomy, right trisegmentectomy, or left trisegmentectomy is performed
      for hilar bile duct carcinoma, the procedure carries a considerable risk of
      postoperative hepatic failure. A technique (embolization of the portal venous
      branches in the liver to be resected) has been used with satisfactory results and
      a low incidence of postoperative hepatic failure after extensive resection of
      normally functioning parenchyma. The detailed mechanisms of volume reduction
      induced by portal venous flow occlusion and hypertrophy of the counterpart lobe
      have not yet been clarified, but similar results have been observed in many
      animal experiments and clinical cases. Two techniques are used for embolization
      of the portal venous branches: the percutaneous transhepatic route and the
      transileocolic route. Fibrin glue, ethanol, gelatin sponge, and cyanoacrylate are
      used for embolization and the degree of compensated hypertrophy of the non
      embolized lobe is influenced mainly by the agents used for embolization.

PMID- 10884989
TI  - [Extended liver resection for hilar cholangiocarcinoma].
AB  - Liver resection for hilar cholangiocarcinoma should be designed for individual
      patients, based on both precise diagnosis of cancer extent and accurate
      evaluation of hepatic functional reserve. Therefore we have developed various
      types of hepatic segmentectomy. Combined caudate lobectomy is essential in every
      patient with separated hepatic confluence. So-called extensive hepatectomy,
      resection of 50% or more of the hepatic mass, includes right lobectomy and right
      or left trisegmentectomy. Right lobectomy with caudate lobectomy is indicated
      when the progression of cancer is predominant in the right anterior and posterior
      segmental bile ducts. The plane of liver transection is along the Cantlie line,
      and the left hepatic duct is divided just at the right side of the umbilical
      portion of the left portal vein. Right trisegmentectomy with caudate lobectomy is
      performed in carcinoma which involves the right hepatic ducts in continuity with
      the left medial segmental bile duct. The umbilical portion of the left portal
      vein is freed from the umbilical plate by dividing the small portal branches
      arising from the cranial side of the umbilical portion. Then the left lateral
      segmental bile ducts are exposed and divided at the left side of the umbilical
      portion of the left portal vein. Left trisegmentectomy with caudate lobectomy is
      suitable for carcinoma which involves the left intrahepatic bile duct in
      continuity with the right anterior segmental bile duct. Liver transection is
      advanced along the right portal fissure. The right posterior segmental bile duct
      is usually divided distal to the confluence of the inferior and superior
      branches.

PMID- 10884990
TI  - [Hepatectomy (parenchyma-preserving) for hilar cholangiocarcinoma].
AB  - The aim of this study was to evaluate the results of parenchyma-preserving
      hepatectomy as surgical treatment for hilar cholangiocarcinoma. Ninety-three
      resected patients with hilar cholangiocarcinoma were included in this study. The
      resected patients were stratified into three groups: the extended hepatectomy
      (EXH) group (n = 66); the parenchyma-preserving hepatectomy (PPH) group (n = 14);
      and the local resection (LR) group(n = 13). The EXH group underwent hepatectomy
      more extensive than hemihepatectomy, the PPH group underwent hepatectomy less
      extensive than hemihepatectomy; and the LR group underwent extrahepatic bile duct
      resection without hepatic resection. Surgical curability of the PPH and EXH
      groups was better than that of the LR group. Surgical morbidity was higher in the
      EXH group(48%) than in the LR group (8%) and the PPH group(14%) (p < 0.01 and p <
      0.05, respectively). The survival rates after resection were significantly higher
      in patients who underwent hepatectomy, including PPH and EXH, than in patients
      who underwent LR (29% vs 8% at 5 years, respectively, p < 0.05). However, no
      significant difference in survival was found between the PPH and EXH groups.
      Univariate and multivariate analysis showed that significant prognostic factors
      for survival were resected margins, lymph node status, and vascular resection. In
      conclusion, PPH may be beneficial in highly selected patients based on cancer
      extent and high-risk patients with liver dysfunction and advanced age.

PMID- 10884991
TI  - [Multidisciplinary treatment of hilar cholangiocarcinoma].
AB  - With advances in surgical techniques, the number of curative resection for hilar
      cholangiocarcinoma has increased. However, the recurrence rate after curative
      resection is significantly high. There is no established adjuvant therapy for
      these patients, although some groups have administered intraarterial infusion of
      5-fluorouracil combined with cisplatin. In our institution, postoperative
      radiation is administered to control remnant tumors at the ductal and surgical
      margins. Extracorporeal radiation is directed at the surgical margins and
      intraluminal radiation at the ductal margins. This has improved the cumulative
      survival rate for cholangiocarcinoma patients who underwent both curative and
      noncurative resection. The 3-year survival rate of those who underwent curative
      resection with and without postoperative radiation is 100% and 28.5%,
      respectively. The longest survival duration among our patients who received
      intraluminal radiation for positive ductal margins were 55 months. Because the
      biological behaviour and radiation sensitivity of the tumors differ among
      individually, these should be determined through molecular biologic studies in
      the future. Such tailored therapy will require multidisciplinary treatment.

PMID- 10884992
TI  - [Management of hilar bile duct carcinoma with high-dose radiotherapy and
      expandable metallic stent placement].
AB  - This article describes our experience with high-dose radiotherapy in combination
      with the placement of expandable metallic stents (EMS) in the management of hilar
      bile duct carcinoma. Between 1988 and 1999, 107 consecutive patients with hilar
      bile duct carcinoma were treated with EMS placement either alone or in
      combination with high-dose radiotherapy. External beam radiotherapy (EBRT) was
      indicated in 101 patients, and in 86 this was combined with intraluminal 192Ir
      irradiation (ILRT, 59-98Gy). EMS were placed after the completion of
      radiotherapy. The 1-, 2-, 3-, and 5-year actuarial survival rates for the
      radiotherapy group were 66.4%, 23.4%, 15.6%, 7.8%, respectively, and the 1- and 2
      year actuarial survival rates for the nonradiotherapy group were 66.4% and 0%,
      respectively. The placement of EMS was useful for the early establishment of an
      internal bile passage in radically irradiated patients and the 1-, 2-, 3-, and 5
      year actuarial patency rates for the radiotherapy group were 56.3%, 45.3%, 35.2%,
      and 23.4%, respectively, and the 1- and 2-year actuarial patency rates for the
      non radiotherapy group were 50.0% and 0% respectively. High-dose radiotherapy,
      consisting of ILRT and EBRT, appears to be feasible in the management of hilar
      bile duct carcinoma, and it offers a survival advantage for patients not suited
      for surgical resection. The placement of EMS assists the internal bile flow and
      lengthens survival after high-dose radiotherapy.

PMID- 10884993
TI  - [Presacral malignant peripheral nerve sheath tumor in a patient with von
      Recklinghausen disease: case report].
AB  - A 32-year-old woman was admitted to our institution with dysuria and pain in the
      left foot. She was diagnosed with von Recklinghausen disease based on the
      physical findings, and an elastic, firm mass was palpable with the fingertip on
      the posterior wall of the rectum. Ultrasonography, computed tomography, and
      magnetic resonance imaging revealed a solid tumor, which measured 8 cm in
      diameter, in the presacral space. The tumor was diagnosed as a presacral solid
      tumor and the tumor was extirpated. The specimen was a 10 x 8 x 8 cm yellowish
      solid tumor weighing 250 g. The histopathologic diagnosis was malignant
      peripheral nerve sheath tumor (MPNST). Presacral MPNST is rarely diagnosed in the
      early stage, and the prognosis for MPNST patients with von Recklinghausen disease
      is relatively poor. Tumor resection with wide surgical margins is necessary and
      close follow-up after surgery is mandatory.

PMID- 10884994
TI  - A survey of nurse practitioners across the United States.

PMID- 10884995
TI  - Bedside urodynamic studies: simple testing for urinary incontinence.
AB  - Through proper evaluation and assessment, a large number of patients suffering
      from urinary incontinence may be effectively treated. Urodynamic studies, which
      are tests used to assess lower urinary tract function, may be performed using
      elaborate machinery or simple equipment found in most office settings. Bedside
      urodynamic studies may be performed without machinery. Patients with symptoms of
      stress incontinence or urge incontinence are candidates for bedside urodynamic
      techniques. Using the assessment tool results, pharmacologic therapy and
      behavioral treatment may be instituted. This article discusses the components of
      bedside urodynamic studies and provides the clinician with improved proficiency
      in assessing urinary incontinence.

PMID- 10884996
TI  - Vascular disease risk markers in diabetes: monitoring & intervention.
AB  - Identifying and treating risk markers for vascular disease in diabetes is
      significant in preventing long-term disabilities and containing health care
      costs. Current research recommends maintaining normal blood glucose levels in all
      diabetes patients. Blood glucose that is elevated for several years is a major
      factor in the development and progression of microvascular diabetes
      complications. Patients play a key role in monitoring vascular disease risk
      markers. This article provides information on the risk markers to monitor,
      microvascular and macrovascular complications, and current therapies to combat
      complication progression.

PMID- 10884997
TI  - Establishing the etiology of thrombocytopenia.
AB  - Hemostasis is dependent on an adequate number of well-functioning platelets in
      the circulating blood. As the number of circulating platelets decreases, the
      chance of bleeding increases. Thrombocytopenia, a platelet count of less than
      150,000 per microliter, is a laboratory finding and not a diagnosis. Therefore,
      once thrombocytopenia is identified, a detailed history, physical examination,
      and further laboratory tests are used to establish an etiology. This article
      reviews the assessment, diagnosis, and treatment of thrombocytopenia.

PMID- 10884998
TI  - Nephrotic syndrome secondary to amyloidosis.
AB  - Nephrotic syndrome represents a constellation of symptoms including
      hyperalbuminuria, hypoalbuminemia, edema formation, hypercholesterolemia,
      hypertension, hypercoagulopathy, and increased infection risk. The hallmark of
      this syndrome is proteinuria greater than 3.5 grams per 24 hours, and the
      clinical features are secondary manifestations of an underlying primary
      glomerular or systemic disease. The objectives of treatment are threefold:
      correcting the primary disease, decreasing the symptoms and secondary effects
      associated with this syndrome, and preventing complications. This article
      presents a case report of a man diagnosed with nephrotic syndrome secondary to
      amyloidosis. The clinical aspects of the disease processes, the diagnostic
      evaluation, the treatment course, and disease management are discussed.

PMID- 10884999
TI  - A differential diagnosis is key.

PMID- 10885000
TI  - The challenges of diagnosing erectile dysfunction in the primary care setting.
AB  - Erectile dysfunction is present in approximately half of all men between the ages
      of 40 and 70. Patients are often reluctant to discuss this problem with their
      practitioner; therefore, unless the practitioner is able to initiate the
      discussion, the diagnosis will not be made and successful treatment will not be
      started. Primary care practitioners have previously received little training in
      taking the sexual history of their patients. In addition, primary care
      practitioners are under increasing pressure to see more and more patients in less
      and less time. Erectile dysfunction is a condition that is relatively easy to
      diagnose using history, physical examination, and laboratory tests at the
      disposal of the primary care practitioner. Although referral to an urologist may
      be necessary, most patients can be successfully treated in the primary care
      setting.

PMID- 10885002
TI  - The patient with erectile dysfunction: psychological issues.
AB  - Erectile dysfunction (ED) affects as many as 30 million men and their partners in
      the United States. Although clinicians now recognize that as many as 80% of cases
      of ED are organic in origin, psychological issues remain important for the ED
      patient.

PMID- 10885001
TI  - Diagnosis and treatment of erectile dysfunction: the process of care model.
AB  - The new era of erectile dysfunction (ED) medicine ushered in by the availability
      of an effective and safe oral medication paves the way toward managing ED in a
      primary care setting. The Process of Care Model for the Evaluation and Treatment
      of Erectile Dysfunction was developed to advance new guidelines for the diagnosis
      and management of ED. This paper discusses these guidelines.

PMID- 10885003
TI  - The role of the NP in the diagnosis and management of erectile dysfunction.
AB  - Erectile dysfunction (ED) affects approximately 30 million men, significantly
      affecting their quality of life and relationships. More and more men are seeking
      help for this problem due to the advent of simpler, less-invasive treatment
      options. Inevitably, nurse practitioners (NPs) in primary care will encounter
      patients with ED. The assessment and diagnosis of ED can be facilitated by using
      a structured decision-making approach, which will promote comprehensive patient
      care. Some primary care NPs may need to increase their own comfort level with
      taking a sexual history, evaluating sexual problems, and knowing when to refer to
      a specialist.

PMID- 10885004
TI  - Factors influencing protease production by two Antarctic strains of
      Stenotrophomonas maltophilia.
AB  - The influence of culture medium buffer capacity, the supplementation of culture
      medium with L-ala and the requirement of calcium for exoprotease production by
      Antarctic psychrotrophic Stenotrophomonas maltophilia strains ANT-1-1 and ANT-7-1
      were examined. When increasing concentrations of calcium chloride (0 to 0.3 g l
      1) were added to culture media, maximum protease production yields increased 70
      75% (ANT-1-1) and 50% (ANT-7-1), while biomass levels showed little difference.
      Calcium was also necessary for optimal activity of proteases. L-ala had no effect
      on protease production. The reduction in buffer capacity, with the consequent
      change in external pH, had a positive effect, enhancing protease yields.
      Secretion of proteases into the medium started at the beginning of the stationary
      phase, corresponding with a rise in pH values up to pH 8.7 and was maximal at 36
      h of culture. These results indicate that the regulation of calcium concentration
      and buffer capacity and also pH monitoring are factors to be considered when the
      design of an industrial culture medium and the optimisation of protease
      production processes using these Antarctic strains are concerned.

PMID- 10885005
TI  - [Survey of pH and water activity in acidified bottled vegetables and meats (home
      processed) in relation to the potential growth of Clostridium botulinum].
AB  - The water activity (aw) and pH of acidified (vinegar) bottled vegetables and meat
      with vegetables--mostly home-canned--was examined in relation to the potential
      growth of Clostridium botulinum. Most products (vegetables or meat with
      vegetables) had water activity above the "per se" inhibitory limit (aw < 0.95)
      for growth of C. botulinum. Regarding pH, 96% of canned vegetables had a pH lower
      than 4.6, but 81% of the canned meat with vegetables had a pH above 4.6. This was
      attributed to the well known buffer effect of food proteins, which makes it
      difficult to lower food pH during acidification with vinegar. It is concluded
      that most bottled meat with vegetables constitute a potential hazard since these
      foods are marketed at room temperature, and botulism toxin may be produced if
      spores are present.

PMID- 10885006
TI  - [Inhibition of Bacillus coagulans growth in laboratory media and in fruit
      purees].
AB  - The growth of two strains of B. coagulans was inhibited in laboratory media at pH
      < or = 4.5, and at water activity (aw) levels of 0.96 for B. coagulans NRS 609
      and 0.95 for B. coagulans ATCC 803. The growth of both strains was also inhibited
      in apple and strawberry purees (pH = 3.5) stored at 37 degrees C for over two
      months. B. coagulans was able to grow in banana puree (pH approximately equal to
      5.0) but acidification of the puree at pH = 3.5 was enough to prevent growth. The
      addition of up to 3,000 ppm vainillin ("natural" preservative) or 1,000 ppm
      potassium sorbate (traditional preservative) at pH higher than the inhibitory
      level previously determined could not prevent growth of B. coagulans in
      laboratory or in fruits, but 100 ppm lysozyme retarded growth in laboratory media
      at different pH levels (from 4.5 to 6.7) and in banana puree. As lysozyme showed
      to be effective at pH < or = 6.7, it might be used to prevent growth of B.
      coagulans at an eventual increment of pH during storage.

PMID- 10885007
TI  - [Meningoencephalitis caused by Herpesviridae family virus in Cuba. 1996-1998].
AB  - Herpesvirus isolation from cerebrospinal fluid (CSF) has proven not to be very
      useful because of its low sensitivity; that is the reason why PCR has
      considerably improved the diagnosis of several viral infections of the central
      nervous system. We studied, by means of PCR, 253 CSF received in our laboratory
      from 1996 to 1998, which had a suspected diagnosis of herpesviral-associated
      neurologic disease (encephalitits or meningoencephalitis). Of these, 182 were
      from HIV seropositive patients and the other 71 were from HIV seronegative. The
      percentage of all positive cases was 22.5% in AIDS patients and CMV was the virus
      most frequently detected (13.7%). We detected a percentage of 29.5 of positive
      cases in immunocompetent individuals, being HSV the virus most frequently found.
      Other herpesviruses (varicella-zoster virus, Epstein-Barr virus, human
      herpesvirus 6) were also detected in some cases in both groups. Finally, we
      obtained clinical data from all positive patients and established a relationship
      with PCR results.

PMID- 10885008
TI  - [Enzymes of white rot fungi involved in lignin degradation].
AB  - The presence of oxidases and peroxidases was tested qualitatively in 12 strains
      of white rot Basidiomycetes. Plate tests with gallic acid, tannic acid, guayacol,
      Poly R-478 and Azure B were used. Fomes sclerodermeus, Phlebia sp. and Pycnoporus
      sanguineus were selected for further studies because they produced the largest
      areas of degradation in all media tested. Poly R-478 degradation and manganese
      peroxidase, lignin peroxidase and laccase activities were measured in glucose
      asparagine (N-sufficient) and Kirk (N-limited) media. The highest activities were
      produced by F. sclerodermeus cultured in glucose asparagine medium.

PMID- 10885009
TI  - [Dictyostelids (Eumycetozoa) from soils of Punta Lara, Province of Buenos Aires,
      Argentina].
AB  - Five taxa of dictyostelid cellular slime molds were isolated from soil and litter
      samples of the relictual gallery forest of Punta Lara (34 degrees 47' S, 58
      degrees 1' W), Province of Buenos Aires, Argentina. Dictyostelium lavandulum, D.
      polycephalum, D. purpureum and Polysphondylium violaceum were identified from
      most samples studied, whereas D. macrocephalum was isolated only once. Strains
      were lyophilized and kept in the BAFC Ceparium. Two additional isolated strains
      were related to D. sphaerocephalum, and to D. mucoroides var. stoloniferum. These
      species were likewise found, among others, in soils of the Iguazu National Park
      (Misiones, Argentina) in 1995.

PMID- 10885010
TI  - Detection of Neisseria meningitidis in cerebrospinal fluid samples from
      suspicious cases of meningococcal meningitis using polymerase chain reaction and
      counterimmunoelectrophoresis.
AB  - Rapid diagnosis of meningococcal disease followed by an early treatment is
      essential. However, blood or cerebrospinal fluid cultures may not be successful
      because antibiotic treatment is often started before proper specimens are
      collected and because bacteria may die during transportation to the laboratory.
      Improvements in antibiotic therapy for specific microorganisms will require the
      use of more than one method for immunodiagnosis. In this study a collection of
      cerebrospinal fluid samples from Brazilian patients was analyzed. Gram stains,
      culture, counterimmunoelectrophoresis and clinical evaluations for meningococcal
      diseases were available. The sensitivity of nested PCR (nPCR) was 73% for
      cerebrospinal fluid of clinically suspected cases, whereas both sensitivity and
      specificity were 100% when subtypes of Brazilian epidemic strains (P1.7, P1.9 and
      P1.15) isolated from the samples were used.

PMID- 10885011
TI  - [Helicobacter pylori infection diagnosis in dyspeptic patients from the City of
      San Luis, Argentina, using invasive methods].
AB  - In this study we present a relationship between different gastroduodenal
      pathologies and Helicobacter pylori infection. We used four diagnosis invasive
      methods for H. pylori infection: urease test (UT), histopathology (H), Gram stain
      (G) and culture (C). The upper gastrointestinal endoscopy of 300 dyspeptic
      patients showed that 71.6% had erosive congestive gastropathies, 13.6% had
      duodenopathies, 5.6% had gastric ulcer, 6.3% had duodenal ulcer and 2.6% had
      probable gastric neoplasia. We also correlated the data of water intake source
      with the pathologies. The percentage of infected patients with H. pylori was
      determined using: a) two simultaneous reference tests (UT and H), 54.3%, b) each
      test UT = 55.0%, H = 59.0%, G = 51.3%, and C = 43.0%. Sex, age and the source of
      water ingested did not show statistically significant differences.

PMID- 10885012
TI  - [Analysis of the simultaneous discharges of neuron pairs in the brain cortical
      microstructures].
AB  - Dynamics of simultaneous discharges of pairs of cortical neurones was studied in
      three behavioural conditions. Parameters of the stimulation applied was shown to
      be encoded in trains of simultaneous unit discharges.

PMID- 10885013
TI  - [Interconnected biochemical processes in striatal neurons induced by activation
      of excitatory, inhibitory, and dopamine inputs].
AB  - Postsynaptic processes induced by glutamate, GABA, and dopamine in dendritic
      spines of inhibitory striatal neurones, were studied. Some functional features
      were revealed in striatal neurones activation of two protein kinases, cAMP
      dependent PKA and cGMP-dependent PKG; presence of calcium/calmodulin-independent
      adenylate cyclase; bidirectional changes of the cAMP concentration with dopamine.
      Rise of the cGMP concentration in striatum seems to be a result of activation of
      the membrane-bound guanylate cyclase via the GABAb receptors. The findings
      suggest that the active protein kinases/phosphatases ratio is affected by calcium
      influx through the NMDA-channels.

PMID- 10885014
TI  - [Unified postsynaptic mechanism of plasticity in the striatum, neocortex,
      hippocampus, and cerebellum].
AB  - The unitary postsynaptic mechanism of plasticity in striatum, neocortex,
      hippocampus and cerebellum involves the LTP/LTD excitation as result of AMPA and
      NMDA receptor phosphorylation/dephosphorylation, while the LTP/LTD of inhibition
      is the result of the GABA receptor phosphorylation/dephosphorylation. It follows
      from this mechanism that when NMDA channels are closed, the determinant role in
      receptor phosphorylation is played by the PKG. When the NMDA channels are open,
      the determinant role in receptor phosphorylation is played by the PKC and CaMKII.

PMID- 10885015
TI  - [Structural basis of the intracortical synchronization of epileptic potentials in
      the sensomotor region of the rat neocortex].
AB  - In control rats, penicillin-induced epileptiform discharges were completely
      synchronous in the neocortex sites at a distance of up to 4 mm from each other.
      Number of the cells decreased by 45.5% during 90 days in isolated cortical slabs
      and the synchronisation disappeared. The data obtained show that the loss of
      large pyramidal neurones of the layer V entailed a loss of the spatial
      synchronisation. The main axonal collaterals of large pyramidal neurones of the
      layer V could be followed horizontally for a distance of up to 2 mm in the
      somatosensory cortex. The neuronal network formed by the large pyramidal neurones
      of the layer V seems to provide a spatial synchronisation in the neocortex.

PMID- 10885016
TI  - [Characteristics of the perception and imagination of emotions in patients with
      focal brain pathology].
AB  - Voluntary components of the emotion perception were shown to be related to the
      left hemisphere temporal area in patients with focal lesions of postero-frontal
      and temporal areas of both hemispheres, whereas the involuntary components
      required involvement of the right hemisphere temporal area. The voluntary
      components of the emotion reproduction are associated with involvement of the
      left hemisphere postero-frontal area, whereas involuntary components of
      perception are related to work of the right hemisphere postero-frontal area. The
      data obtained suggest that the voluntary (conscious) recognition and reproduction
      of emotions are mainly related to the sensory and motor speech centres of the
      left hemisphere, whereas involuntary those involve symmetrical areas of the
      opposite hemisphere.

PMID- 10885017
TI  - [The information theory of emotions: the psychophysiological study of the mental
      imagination of joy].
AB  - An interhemisphere distribution of the EEG frequency and amplitude and its
      dependence on intensity of an imagined emotional experience, was studied in 20
      subjects. A positive correlation was found between the information scale and the
      EEG alpha-frequency band, as well as between the intensity of imagined desire and
      EEG delta- and theta-waves in the left hemisphere.

PMID- 10885018
TI  - [Prophylactic effect of antioxidant Aekol on behavioral (psychoemotional)
      disturbances caused by chronic stress in rats].
AB  - Antioxidant preparation "Aekol" containing vitamins A, E, and K3, was shown to
      possess antidepressant properties and to exert a prophylactic effect on
      behavioural (psychoemotional) disturbances induced by a chronic stress in rats: a
      depressive condition associated with an enhanced anxiety, elimination of
      individual differences in behaviour, weakening of the relationships among
      behavioural parameters recorded in the same animal in three different tests.

PMID- 10885019
TI  - [Evaluation of velocity of vertical learning of the habitable space for complex
      behavioral experiments in rats].
AB  - A selection of laboratory animals for complex behavioural experiments is of a
      significant importance for obtaining objective results. The problem of the
      selection seems to be solved by means of the proposed assessment of vertical
      learning of an habitable space. The assessment test is based on investigative
      activity of the animals under conditions of a new surrounding. The test allows to
      divide the rats into four types.

PMID- 10885020
TI  - [Pharmacological reminder of the emotional condition facilitates the amnestic
      memory trace retrieval].
AB  - Passive avoidance reflex was shown to be differently reproduced in rats. The
      reproduction was more stable in rats with a higher level of learning. Amnestic
      effects induced seizures were shown to depend on relationships between the
      intensity of learning and the intensity of seizures. Unconditioned stimuli acting
      as a reminder decreased the amnestic effects of seizures. Learning process
      significantly reduced the seizure severity. A dissociated convulsive state was
      reproduced with the aid of a pharmacological reminder of anxiety formed in the
      course of learning. Haloperidol produced anxiety and suppressed amnestic effects
      of seizures, facilitated conditioning in rats with a low level of learning.

PMID- 10885021
TI  - [EEG study of the anxiolytic effect of scopolamine].
AB  - Effect of the central M-cholinolytic scopolamine on spatial organization of the
      rat brain electrical activity was studied under conditions of high and low
      emotional-stress responses. The EEG changes were estimated by 840 parameters. A
      possibility of the EEG discrimination by means of interstrain differences in
      responses to scopolamine, was shown. A more obvious decrease in spectral power
      and potentials coherence was revealed in Maudsley Reactive rats (MR) as compared
      with the Maudsley Nonreactive rats (MNRA), in parieto-temporal and occipital
      areas of the right hemisphere, and the reverse interrelationship occurred in the
      anterior parts of the right and posterior parts of the left hemisphere. These
      findings suggest some specifics in the spatial distribution of the maximum
      scopolamine action foci depending on the initial emotional level. Changes
      occurring under the scopolamine effect in different EEG frequency bands are
      different in the MR and the MNRA rats. The findings are discussed in respect to
      the EEG indices of anxiolytic component of cholinergic regulation of the brain
      activity.

PMID- 10885022
TI  - [Functional organization of local neuronal networks in the cat neocortex.
      Dependence on the food motivation].
AB  - The multiple unit activity (MUA) from clusters of adjacent neurones in deep
      layers of the frontal and motor cortex was recorded in alert cats with different
      levels of alimentary motivation. Up to 7 spike trains were selected from the MUA.
      Neurones in the local circuits could be divided into 2 groups: large neurones
      with prevailing divergent characteristics, and small neurones with prevailing
      convergent characteristics. A 24-hour food deprivation altered the cross
      correlation interneuronal connections with a time delay within the range of 2 to
      100 ms.

PMID- 10885023
TI  - [Characteristics of behavior of WAG/Rij rats with genetic susceptibility to
      absence epilepsy].

PMID- 10885024
TI  - [Changes in the redox potential in the rat brain tissue during paradoxical sleep
      events].

PMID- 10885025
TI  - [Strategy for primary prevention of coronary heart disease based on results of
      health check-up].
AB  - To investigate one of the strategies for effective primary prevention of coronary
      heart disease (CHD) in employees, the future morbidity of CHD was predicted from
      the results of an annual health check-up. The decrease in morbidity by measures
      against coronary risk factors was estimated with simulations. By a CHD risk
      prediction algorithm based on the Framingham Study, the 10-yr incidence of CHD
      was predicted in 6,444 male employees of a manufacturing company according to the
      results of a health check-up in 1998: age, total cholesterol (TC), HDL
      cholesterol (HDL-C), blood pressure (BP), diabetes mellitus, and smoking habit.
      The decrease in CHD incidence obtained by a decrease in TC, increase in HDL-C,
      decrease in BP, control of diabetes mellitus, or quitting the smoking habit was
      estimated with simulations by means of the algorithm. The mean +/- SD in 6,444
      employees was 45 +/- 11 yr for age; 121 +/- 16 and 79 +/- 10 mmHg for systolic
      and diastolic BP, respectively; 193 +/- 34, 53 +/- 13, and 98 +/- 18 mg/dl for
      TC, HDL-C, and fasting blood sugar, respectively; 4.80 +/- 0.58% for HbA1c; and
      44% for the frequency of the smoking habit. Among 6,444 males, 455 (7.1%) were
      predicted to suffer from CHD for 10 yr ahead. If TC was decreased to less than
      200 mg/dl in all 2,614 males (N) with TC > or = 200 mg/dl, the decrease (D) in
      the predicted number of employees with CHD was 64; namely, a reduction of TC to
      less than 200 mg/dl in 41 males (N/D) with TC > or = 200 mg/dl was estimated to
      decrease the number of CHD patients by one. Similarly, the D and N/D were 38 and
      35 for reduction in BP to less than 140/90 mmHg; 20 and 17 for control of
      diabetes mellitus; and 90 and 32 for quitting the smoking habit, respectively. A
      measure against diabetes mellitus was the most effective in respect of N/D, but
      the predicted total reduction was small (D = 20). On the other hand, a measure
      against the smoking habit was estimated to have a relatively small N/D as well as
      the largest D. In 5,386 employees with at least one of the risk factors of TC >
      or = 200 mg/dl, HDL-C < 45 mg/dl, BP > or = 130/85 mmHg, diabetes mellitus, and
      the smoking habit, the normalization of all risk factors was estimated to
      decrease by 230 CHD patients (D = 230, N/D = 23). These results suggest that the
      strategy for effective primary prevention of CHD in employees of a company should
      include at first, quitting the smoking habit supported by total prohibition of
      smoking within company facilities, followed by measures against hyperlipidemia,
      hypertension and diabetes mellitus.

PMID- 10885026
TI  - [Impact of indirect factors on the growing prevalence of workers with abnormal
      findings in periodic general health examinations: a survey on the definition and
      detection of such abnormal workers by occupational health organizations].
AB  - The prevalence of workers with abnormal findings in periodic general health
      examinations (PGHEx) has been growing recently in Japan and reached 41.2% in
      1998. To clarify the indirect factors related to such an increase in workers with
      abnormal findings in the PGHEx, we carried out a questionnaire survey on the
      content of the statutory notification form of results of the PGHEx among a
      representative sample of 136 Occupational Health Organizations (OHOs). Questions
      on how those workers with abnormal findings were defined and detected and when
      the definition and the reference intervals for total cholesterol became available
      were included. Of the 107 OHOs which answered the questionnaire, 85 were included
      in the analyses because they actually calculated the number of workers with
      abnormal findings in each company and helped the employer fill out the
      notification form. The results revealed that there was no standardized definition
      of workers with abnormal findings in the PGHEx. Both reference intervals of items
      in the PGHEx and algorithm in detecting workers with abnormal findings in the
      PGHEx varied among the OHOs. When detecting the workers, 13 OHOs (15.3%) selected
      them taking into consideration medical background factors such as previous
      results of the PGHEx and current medical treatment. From the late 1980s to the
      early 1990s, many OHOs modified the definition of workers with abnormal findings,
      and have tended to reduce the upper limit of the reference interval for serum
      cholesterol. This is mainly due to amendment of the Industrial Safety and Health
      Law and a new recommendation for a reference interval/value proposed by the
      related scientific society. Although the prevalence of workers with abnormal
      findings in the PGHEx has continuously increased, it is not valid to compare the
      prevalence over the years because of modification in the definition of such
      workers. The prevalence of workers with abnormal findings in the PGHEx, which is
      one of the most important indices of the state of occupational health, should be
      measured by using an objective definition and be compatible with the future
      system of health examination for Japanese workers.

PMID- 10885027
TI  - [The risk of colorectal adenomatous polyp in relation to serum total cholesterol
      levels in Japanese men classified by age group].
AB  - In order to investigate the relationship between the risk of colorectal cancer
      and serum total cholesterol (TC) levels, we studied the relationship between the
      risk of colorectal adenomatous polyp and high TC levels in Japanese men aged from
      40 to 59 at a manufacturing company. We first diagnosed 283 subjects as having
      adenomatous polyp (AD) or normal (C), identified by means of an immunological
      fecal occult blood detection test and total colonofiberscopic examination (TCF),
      and then selected 94 subjects after excluding the patients with diseases possibly
      influencing TC. We classified the subjects into two age groups (40-49 and 50-59)
      and conducted a statistical analysis of AD and C groups by means of a two tailed
      t-test. The mean values for TC (DTC), which had been obtained within 3 months
      before TCF, were significantly different (p < 0.001 95% CI 15.79-48.49) for those
      in their 40s, but were not different for those in their 50s. In order to check
      the stability of the data, we analyzed the mean values for DTC and BTC, which had
      been obtained within 15 months. The results showed the same trend for those in
      their 40s (p = 0.001 95% CI 10.76-40.87). The mean DTC and BTC values were again
      not significantly different for those in their 50s. We further divided the
      subjects into the lower (-181 mg/dl) and higher (209 mg/dl-) DTC values and
      conducted further statistical analysis with Fisher's exact test. The results were
      significant in the 40-49 age group (p = 0.004), in the odds ratio (13.75 95% CI
      2.32-81.49), but showed no significant difference in the 50-59 age group. The
      mean LDL-cholesterol values within 3 months before TCF were significantly
      different in the 40-49 age group (p < 0.001 95% CI 15.22-47.70) and were not
      different in the 50-59 age group. There was no statistical difference in the mean
      values for HDL-cholesterol, triglyceride and body mass index in either age group.
      From these results, it can be concluded that the risk of colorectal adenomatous
      polyp was associated with a higher serum total cholesterol level in the 40s, and
      seemed to indicate a close relationship with the risk of colorectal cancer.

PMID- 10885028
TI  - [A case of asbestos induced lung cancer in a thermal power plant].

PMID- 10885029
TI  - [Russian medicinal plants--an inexhaustible source for creating new highly
      effective medicinal-prophylactic substances and biologically-active food
      additives].
AB  - The status of businesses in Russia and abroad on production of the biologically
      active food additives, and in particular is considered on the basis of plant raw.
      Taking into account the presence in Russia of the richest raw plant market, and
      in a view of deficit in the country of preventive herbal drugs the development of
      the long-term state target program of their production and creation of the
      effective system of standardization and control behind quality, safety and
      effectivency of operation of these drugs is offered.

PMID- 10885030
TI  - [Role of free radical oxidation processes in the pathogenesis of infectious
      diseases].
AB  - Recent literature data on the mechanisms responsible for oxidative stress at
      infectious diseases and methods of their correction are reviewed.

PMID- 10885031
TI  - [Bilirubin as an endogenous intermediary in the activation of CYP1A1 expression
      upon exposure to ultrasound].
AB  - The induction of cytochrome P4501A1 (CYP1A1) enzyme activity reflects the
      increased ligand-dependent transcriptional activity of the cognate CYP1A1 gene.
      The list of ligands includes various xenobotics such as polycyclic and
      halogenated aromatic hydrocarbons. Until recently, similar role for endogenous
      compounds was unknown. In the present study the ability of the endogenous heme
      metabolite, bilirubin, to regulate CYP1A1 activity was examined. The following
      parameters were investigated: expression of CYP1A1 in rat liver at a level mRNA,
      protein and functional activity under at the experimental rising of blood
      bilirubin level. The influence of local ultrasound contact treatment of rats
      hepatic area in vivo (the intensity 0.4 W/cm2 and duration time of 10 minutes) on
      blood unconjugated bilirubin concentration and parameters of CYP1A1
      transcriptional activity was also investigated. The ultrasound contact action on
      rat hepatic are increased blood unconjugated bilirubin concentration. The rise of
      bilirubin levels of in rat blood after intravenous administration of bilirubin as
      well as after ultrasound treatment was accompanied by increased mRNA CYP1A1,
      protein and functional activity of CYP1A1. The comparison of these data with that
      of time-dependent changes of parameters of CYP1A1 transcriptional activity under
      ultrasound action and experimental rising of blood bilirubin level suggest that
      induces CYP1A1 and may be an intermediate in the activation of CYP1A1 expression
      under ultrasound action.

PMID- 10885033
TI  - [Metabolic changes in rat liver in the recovery period after hyperthermic
      exposure].
AB  - The metabolic changes in rat liver were studied during a reduction period after
      the overheating (25 min, 42 degrees C) using the isolated organ perfusion. First
      six hours after the treatment were characterised by a decrease of the respiration
      rate, the activation of glycolysis and an exhaustion of hepatic carbohydrate
      resources. The development of adaptive reaction resulted in the recovery of
      respiration rate to 18 h. This may provide subsequent restoration of hepatic
      metabolism and normalisation of the organ functioning.

PMID- 10885032
TI  - [Processes of protein biosynthesis in cardiac muscle and cardioprotective effect
      of mu-opiate receptor ligands in immobilization stress].
AB  - Immobilization stress leads to the increase of 99mTc-pyrophosphate accumulation
      in the heart that points to the cardiomyocyte damage. The stress-reaction was
      accompanied by a decrease of protein synthesis rate in the heart muscle and
      immunoreactive insulin level in blood plasma and increase of blood plasma
      cortisol and aldosteron. Pretreatment with agonists mu-opioid receptors DALDA and
      DAGO (0.1 mg/kg intraperitonealy (i.p.) twice during stress) completely prevented
      the stress-induction decrease of myocardial protein synthesis rate, heart damage
      and hormonal imbalance. Cycloheximide administration (0.3 mg/kg i.p.) increased
      rats myocardial membrane injury during immobilization and reduced
      cardioprotective effect of DALDA.

PMID- 10885034
TI  - [Participation of the cytochrome P450-dependent biotransformation system in
      realizing the toxic effects of acrylamide].
AB  - Neuro-, hepato- and geno-toxic effects of the industrial xenobiotic, acrylamide,
      were studied in intact rats and in rats with induced phenobarbital- and 3
      methylholanthren-dependent isoforms of cytochrome P-450. The induction of the
      first isoform increased neuro- and hepato-toxic effects of acrylamide and
      decreased the extent of cell genome damage. Activation of the 3-methylholanthren
      dependent cytochrome had no influence on the toxicity of this xenobiotic.
      Realisation of toxic effects of acrylamide may involve a decrease of the
      carbohydrate energy metabolism, but in the intact organism these processes
      precede the induction of the phenobarbital-dependent cytochrome P450.

PMID- 10885035
TI  - [Insular system of animals in a chronic heparin deficiency].
AB  - The chronic heparin deficiency achieved by long-term treatment (for 3 weeks) with
      protamine-sulfate is accompanied by the development of stable hyperglycemia,
      decreased glucose tolerance, and the appearance of insulin resistance.
      Administration of exogenous heparin promotes the restoration of normoglycemia.

PMID- 10885036
TI  - [Comparative characteristics of vanadium-containing compounds, possessing insulin
      like effects].
AB  - The serum glucose concentration, HbAc1, fructoseamine, the activity of AST, ALT,
      amylase, glycogen content and glucokinase activity in rat hepatocytes were
      examined in streptozotocin-diabetic rats during long-term orthovanadate and
      vanadyl sulphate treatment. The improvement of this parameters were demonstrated
      after oral orthovanadate and vanadyl sulphate administration. However, insulin
      mimetic properties of vanadyl sulphate were more marked in comparison with
      orthovanadate. LD-50 and cytotoxicity analysis in isolated hepatocytes showed
      that vanadyl sulphate was less toxic than orthovanadate.

PMID- 10885037
TI  - [Effect of thyroxine on the activity of some enzymes of energy metabolism in bone
      marrow myeloid cells and blood neutrophils from piglets].
AB  - The influence of thyroxine on the activities of enzymes of energy metabolism
      (hexokinase, 6-phosphofructokinase, pyruvate kinase, lactate dehydrogenase,
      glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase, cytochrome c
      oxidase) was investigated in bone marrow myeloid cells and blood neutrophils of 3
      10-day old neonatal piglets. Data obtained suggest different responsiveness of
      energy metabolism enzymes to thyroxine action. Repeated hormone injections
      resulted in the preferential stimulation of enzymes involved in oxidative stages
      of carbohydrate catabolism in animal myelocaryocytes, while the activities of
      anaerobic enzymes in these cells were less affected. At the same time glycolytic
      enzymes in neutrophil granulocytes showed higher sensitivity to thyroxine action
      than enzymes catalyzing oxidative stages of energy metabolism.

PMID- 10885038
TI  - [level of 7alpha-hydroxycholesterol in blood plasma as an indicator of
      cholesterol catabolism in hyperlipidemia and with hypolipidemic therapy].
AB  - The effect of micronized fenofibrate (Lipanthyl 200 M, Laboratoire Fournier,
      France, in dose 200 mg per day) on the serum level of 7 alpha-hydroxycholesterol
      (7 alpha-(OH)C) was studied in 10 men (aged 31-60 years) with hyperlipidemia
      (total C > 6.5 mmol/l). The levels of 7 alpha-(OH)C as well as that of total C,
      LDL C, VLDL C and HDL C and triglycerides (Tg) were measured before Lipanthyl 200
      M treatment (point 0) and after 1, 2 and 3 months of the drug administration. The
      content of 7 alpha-(OH)C was determined by the reversed phase HPLC after the
      enzymatic conversion of serum 7 alpha-(OH)C to 7 alpha-(OH)-4-cholesten-3-one in
      cholesterol oxidase reaction. 7 beta-(OH)C was used as the internal recovery
      standard. Lipanthyl treatment resulted in considerable reduction of total C, VLDL
      C and LDL C levels and 7 alpha-(OH)C content. After the second and third months
      of therapy serum levels of 7 alpha-(OH)C were significantly reduced from 1.3 +/-
      0.1 to 0.8 +/- 0.2 and 0.7 +/- 0.1 mumol/l; (P < 0.02). The decrease of 7 alpha
      (OH)C content was associated with the decrease in Tg and VLDL C levels. Thus, our
      data suggest that the level of 7 alpha-(OH)C of in human serum may be used as an
      indicator of intensity of cholesterol oxidation into bile acids.

PMID- 10885039
TI  - [Leukocyte elastase in blood plasma from tuberculosis patients and its role in
      disturbances of blood coagulation regulatory processes].
AB  - 53 patients with lung tuberculosis were divided in 3 groups in accordance with
      severity of disease. Leukocyte elastase, cationic proteins in neutrophils,
      activities of alpha 1-proteinase and alpha 2-macroglobulin were determined in
      patients' plasma. Thromboelastographic, coagulating, fibrinolytic indices, and
      antithrombin III activity were also determined in 28 patients of all 3 groups.
      Results demonstrated the high level of leukocyte elastase (6-fold more than
      normal) in plasma of patients with acute tuberculosis process. This group of
      patients demonstrated activation of intravascular coagulation proceeded on the
      background of significant decrease (up to 60%) of AT III activity. CONCLUSION:
      Acuity and severity of tuberculosis process in lung may be characterized by high
      activity of leukocyte elastase. Degranulating activity of neutrophils and
      releasing of elastase are the reason of AT III deficiency and increasing of
      intravascular coagulating activity in tuberculosis patients.

PMID- 10885040
TI  - Addiction or dependence?

PMID- 10885041
TI  - Conversation with Jim Rankin.

PMID- 10885042
TI  - Alcohol screening and brief intervention: dissemination strategies for medical
      practice and public health.
AB  - This paper introduces the concept of risky drinking and considers the potential
      of alcohol screening and brief intervention (SBI) to reduce alcohol-related
      problems in medical practice and in organized systems of health care. The
      research evidence behind this approach is reviewed. Potential strategies for the
      dissemination of SBI to systems of health care are then discussed within the
      context of a public health model of clinical preventive services. There is an
      emerging consensus that SBI should be promoted in general healthcare settings,
      but further research is needed to determine the best ways to achieve widespread
      dissemination. In an attempt to provide an integrative model that is relevant to
      SBI, dissemination strategies are discussed for three target groups: (1)
      individual patients and practitioners; (2) health care settings and health
      systems; and (3) the communities and the general population. Dissemination
      strategies are considered from the fields of social change, social science,
      commercial marketing and education in terms of their potential for translating
      SBI innovations into routine clinical practice. One overarching strategy implicit
      in the approaches reviewed in this article is to embed alcohol SBI in the more
      general context of preventive health services, the utility of which is becoming
      increasingly recognized as a critical supplement to more traditional clinical
      medicine.

PMID- 10885043
TI  - Cognitive impairment among methadone maintenance patients.
AB  - AIMS: To compare the cognitive performance of methadone maintenance patients
      (MMPs) and a matched sample of non-heroin-using control subjects, and to
      ascertain risk factors for poorer cognitive performance. DESIGN: Matched control
      study. SETTING: Sydney, Australia. PARTICIPANTS: Thirty MMPs and 30 non-heroin
      using controls, matched for age, gender and education. FINDINGS: The MMP group
      had significantly higher rates than controls of alcohol dependence, heroin
      overdose and head injury. There was no difference between the groups on pre
      morbid functioning. The MMP group performed significantly poorer than controls on
      all of the neuropsychological domains measured: information processing,
      attention, short-term visual memory, delayed visual memory, short-term verbal
      memory, long-term verbal memory and problem solving. A life-time diagnosis of
      alcohol dependence and the number of non-fatal heroin overdoses were independent
      significant predictors of poorer cognitive performance. CONCLUSIONS: In addition
      to high rates of psychiatric morbidity, MMPs also show cognitive deficits
      compared to matched controls. A history of alcohol dependence and repeated
      exposure to overdose increase the likelihood of cognitive impairment. The current
      study does not rule out the possibility of other factors, that were not measured,
      that may contribute to cognitive impairment among this MMPs.

PMID- 10885044
TI  - The effects of offering free treatment to street-recruited opioid injectors.
AB  - AIMS: The goal of this investigation was to assess the treatment entry impact of
      offering free treatment to street-recruited injecting opioid users, and to
      determine which variables differentiated subjects who entered treatment when it
      was free, compared to those who entered when they had to pay for treatment.
      DESIGN: Three hundred and sixty-two out-of-treatment opioid injectors, recruited
      through street outreach, were randomly assigned to receive or not receive a
      coupon for 90 days of free substance abuse treatment. Demographics, desire for
      treatment, drug use and HIV risk behaviors were assessed prior to assignment.
      FINDINGS: Subjects were characterized by frequent and long-term drug use,
      numerous arrests, a variety of behaviors that placed them at risk for HIV, and
      ambivalence about entering substance abuse treatment. Offering free treatment led
      to significantly greater treatment entry (53% vs. 33%) and retention (155 days
      vs. 83 days). Entry into free treatment was particularly high, compared to those
      who had to pay for treatment, among subjects who had never been in treatment (43%
      vs. 23%) and those who reported that they did not want to enter treatment (24%
      vs. 6%). Subjects who entered free treatment were significantly less likely to
      have family problems than those who paid for their treatment. CONCLUSIONS: Opioid
      addicts recruited on the street and offered free methadone maintenance treatment
      are likely to enter and remain in treatment, even if they have never been in
      treatment before or claim not to want treatment. Different treatment approaches
      may be necessary if such subjects are motivated more by the removal of financial
      obstacles than other factors, such as family problems.

PMID- 10885045
TI  - Effects of increasing income on polydrug use: a comparison of heroin, cocaine and
      alcohol abusers.
AB  - AIMS: To assess how income affects hypothetical drug and non-drug purchasing
      decisions. PARTICIPANTS AND SETTING: Ninety-four subjects (26 heroin abusers, 28
      cocaine abusers, 15 alcohol abusers and 25 non-drug using controls) were
      recruited from advertisements. INTERVENTION: Subjects were exposed to six
      conditions in which they "purchased" drugs as well as food, housing, and
      entertainment as income rose from $30 to $560 per day. FINDINGS: Heroin abusers
      selected significantly more hypothetical heroin and cocaine as income rose and
      demand for these two drugs was income elastic, with purchases rising in greater
      proportion than income. Cocaine abusers significantly increased purchases of, and
      showed income elastic demand for, cocaine and alcohol. Among alcohol abusers,
      significant increases in purchases and income elastic demand were found for
      alcohol and cigarettes, but not for other drugs. Across all four groups, demand
      for rent and food were income inelastic, such that purchases did not rise in
      proportion to the changes in income, while demand for entertainment was income
      elastic. Hypothetical choices were reliable between and within subjects, and drug
      choices were correlated with urinalysis results and life-time years of drug use.
      CONCLUSIONS: Income is an important variable in understanding choices for drug
      and non-drug commodities across a variety of substance-abusing populations.

PMID- 10885046
TI  - Effects of low-dose alcohol exposure on simulated merchant ship handling power
      plant operation by maritime cadets.
AB  - AIMS: Under current US Department of Transportation (DOT) regulations, some
      commercial vehicle operators are subject to sanctions for having > or = 00.04 g%
      blood alcohol concentrations (BACs) on the job. This study investigated the
      effects of alcohol (between 0.04 and 0.05 g% BAC) on the simulated operation of a
      commercial ship's power plant. DESIGN: A balanced placebo design was used in
      which alcohol administration was fully crossed with expectancy that alcohol was
      administrated. SETTING: The study was conducted at the Massachusetts Maritime
      Academy, Buzzards Bay, MA, USA. PARTICIPANTS: Participants were 18 volunteer
      engineering students in their senior year, at least 21 years of age, with
      previous experience on the diesel simulator. INTERVENTION: Following a baseline
      trial on day 1, on day 2 participants were randomized to expectancy (told alcohol
      or placebo) and beverage (receive alcohol or placebo). The dosage was 0.6 g/kg
      for males and 0.5 g/kg for females. In both baseline and performance days,
      participants were randomized to one of four diesel simulator scenarios, each
      replicating a system failure in a power plant subsystem (e.g. main propulsion,
      electrical generating). MEASUREMENT: Performance was measured by time required
      for problem identification and remediation. FINDINGS: A main effect for alcohol
      administration was found. In the alcohol condition, simulator performance time
      was almost twice as long (351 sec) as on the placebo condition (186 sec). The
      expectancy effect was not significant. CONCLUSION: These findings support the
      current federal policy on the hazards of this low alcohol level within the
      context of commercial shipping.

PMID- 10885047
TI  - Relationships of drinking behaviour, gender and age with reported negative and
      positive experiences related to drinking.
AB  - AIMS: To assess associations between drinking behaviour, gender and age with
      reported experiences related to drinking. DESIGN: Cross-sectional survey. SETTING
      AND PARTICIPANTS: Interviews were performed in 1992 with a representative sample
      of the Finnish population between 15 and 69 years of age (N = 3446).
      MEASUREMENTS: Annual intake of alcohol, frequency of drunkenness, and 14 negative
      and eight positive reported experiences related to drinking. FINDINGS: Logistic
      regression models showed that overall intake and frequency of drunkenness were
      independently associated with almost all reported positive and negative
      consequences of drinking. Women more commonly reported that drinking had helped
      them to sort out interpersonal problems at home or in the work-place, to feel
      more optimistic about life, and to express their feelings. Men more commonly
      reported that drinking had helped them to be funnier and wittier and to get
      closer to the opposite sex. Drunken driving was markedly male behaviour, but
      women more commonly reported other types of reckless behaviour and adverse
      consequences of drinking. However, men more commonly said they were criticized by
      family for their drinking. With the exception of health problems, both positive
      and negative consequences of alcohol were more common among younger drinkers.
      CONCLUSIONS: Once overall intake and frequency of drunkenness were controlled
      for, significant differences between men's and women's perceptions of the costs
      and benefits of alcohol consumption emerged. Men tended to perceive more hedonic
      benefits while women perceived more functional benefits. Women reported behaving
      more recklessly in drinking situations. In light of the results, women were not
      under selective social control.

PMID- 10885048
TI  - The assessment of alcohol expectancies in school children: measurement or
      modification?
AB  - AIMS: Earlier research has suggested that measuring children's positive alcohol
      related expectancies could have the undesirable side effect of increasing them.
      This has been reported for an instrument that only measured positive expectancies
      and used a puppet-reference. The present study investigated whether this increase
      was still found using an unbiased instrument. Further, it was tested whether the
      assessment method with puppets influenced children's expectancies. DESIGN:
      Children were assigned randomly to respond on an unbiased expectancy
      questionnaire in one of two assessment conditions: with reference to a puppet (P)
      or without reference to a puppet (Q). One month later, children were again
      administered one of the two assessment conditions, resulting in four assessment
      orders (PP, PQ, QP, QQ). SETTING AND PARTICIPANTS: Three hundred and ninety-five
      second- to fifth-graders were administered one of the two methods in their
      schools and 260 children were measured a second time, 1 month later.
      MEASUREMENTS: A questionnaire measuring children's positive and negative
      expectancies was developed that could be administered with or without a puppet
      reference. FINDINGS: A large direct response-effect was found: in the puppet
      condition, children scored higher on positive but not on negative expectancies. A
      smaller indirect measurement-effect was found at borderline significance:
      children who had used the puppet method 1 month earlier had significantly
      stronger positive expectancies than children who had used the questionnaire
      earlier. CONCLUSIONS: The present results confirm earlier indications that
      measuring children's positive expectancies may have the undesirable side effect
      of increasing them. This can be avoided by measuring children's expectancies with
      an unbiased questionnaire without a puppet-reference.

PMID- 10885049
TI  - Natural recovery is the only recovery.

PMID- 10885050
TI  - Natural recovery from alcohol and drug problems: methodological review of the
      research with suggestions for future directions.
AB  - AIMS: The methodology of studies that reported data on individuals who recovered
      from an alcohol or other drug problem (cigarette smokers were excluded) without
      formal help or treatment were reviewed. DESIGN/MEASUREMENTS: Potential studies
      were identified (a) through computerized literature searches, (b) by reviewing
      references from key publications and (c) by correspondence with researchers in
      the field. Studies had to (a) be in English, (b) be published, in press, or
      presented before the end of 1997, (c) report original results or be part of an
      original survey and (d) separately report respondents whose recoveries were and
      were not attributable to treatment. No case studies were included. Eligible
      studies were evaluated with respect to meeting criteria for (a) natural recovery,
      (b) methodological rigor and (c) reporting demographic and substance abuse
      history variables. FINDINGS: Until 1997 only 38 articles (40 different respondent
      samples) met the inclusion criteria for this review. This small number of studies
      is not surprising, as natural recovery from substance abuse is a relatively new
      area of study. Moreover, the majority of the 38 articles were published in the
      past 8 years. For most studies, descriptions of the respondent samples at pre-
      and post-recovery were seriously deficient. Alcohol was the most studied drug,
      with heroin a distant second. Low-risk drinking (78.6%) and limited drug use
      (46.2%) were commonly reported outcomes in natural recovery studies. CONCLUSIONS:
      Based on this review, future natural recovery studies should: (a) report
      respondents' demographic characteristics at the time of their recovery; (b)
      describe respondents' pre-recovery problem severity; (c) explore in some depth
      what factors, events or processes are associated with the self-change process;
      (d) provide corroboration of respondents' self-reports; (e) examine factors
      related to the maintenance of recoveries; (f) conduct interviews with individuals
      who have naturally recovered from cocaine, marijuana and polydrug abuse; (g)
      include a second interview at a later time to examine stability of natural
      recoveries; and (h) require a minimum 5-year recovery time frame.

PMID- 10885051
TI  - Studies on natural recovery from alcohol dependence: sample selection bias by
      media solicitation?
AB  - AIMS: To assess the selection bias of recruiting participants in studies on
      natural recovery from alcohol dependence through media solicitation. DESIGN: Two
      samples with different recruitment strategies are compared. SETTING: Media
      solicitation and general population. PARTICIPANTS: Sample 1 consists of 176
      alcohol-dependent individuals remitted without formal help and recruited through
      media solicitation, sample 2 consists of 32 natural remitters derived from a
      representative general population study with a sample size of 4075 respondents
      and a response rate of 70.2%. MEASUREMENTS: Several triggering mechanisms and
      maintenance factors of remission were assessed in a personal interview using
      standardized questionnaires. FINDINGS: Results of logistic regression analyses
      show that media-solicited subjects were more often abstinent in the last 12
      months, were more severely dependent, were less satisfied with eight life domains
      prior to remission and showed higher scores in a coping behaviour measure.
      Besides these major differences from the multivariate analysis, media subjects
      revealed more health problems prior to remission, experienced more social
      pressure to change drinking behaviour, and showed differences in reasons for not
      seeking help. CONCLUSIONS: Media solicitation leads to a sample selection bias in
      research on natural recovery from alcohol dependence. When measures to foster
      self-change are derived from such studies, findings from representative samples
      have to be considered.

PMID- 10885052
TI  - Natural and treatment-assisted recovery from gambling problems: a comparison of
      resolved and active gamblers.
AB  - AIM: An exploratory study was conducted to understand the process of recovery
      from gambling problems. DESIGN: Media recruitment was used to identify a resolved
      (n = 43) and a comparison group of active pathological gamblers (n = 63).
      PARTICIPANTS: Participants showed evidence of significant problems related to
      gambling as well as high rates of co-morbid mood and substance use disorders. The
      median length of resolution was 14 months with a range of 6 weeks to 20 years.
      FINDINGS: Resolved gamblers reported a variety of reasons for quitting gambling,
      related mainly to emotional and financial factors. They did not experience a
      greater number of precipitating life events compared with active gamblers but did
      report an increase in positive and a decrease in negative life events in the year
      after resolution. Both resolved and active gamblers who had relatively more
      severe problems were more likely to have had treatment or self-help involvement,
      whereas those with less severe problems, if resolved, were "naturally recovered".
      CONCLUSIONS: The results support the need for a continuum of treatment options
      for problem gamblers and provide helpful information about recovery processes.

PMID- 10885053
TI  - Injecting drug users in Edinburgh have a high rate of recidivism.

PMID- 10885054
TI  - Direct coupling of microcolumn liquid chromatography with in-tube solid-phase
      microextraction for the analysis of antidepressant drugs.
AB  - The direct coupling of in-tube solid-phase microextraction (in-tube SPME) with
      microcolumn liquid chromatography (micro-LC) has been investigated for the
      analysis of antidepressants in human urine. The use of in-tube SPME has been
      clearly shown to be advantageous for the on-line coupling of the SPME method, as
      the sample pretreatment technique, with micro-LC as the separation technique.
      This is because much smaller amounts of the sample solutions, desorption solvents
      and the mobile phase are required compared with conventional SPME-LC systems. The
      parameters for preconcentration have been investigated for the extraction
      capillary with the newly developed 'wire-in-tube' configuration.

PMID- 10885055
TI  - Studies on neurosteroids. Part XIII. Characterization of catechol estrogens in
      rat brains using liquid chromatography-mass spectrometry-mass spectrometry.
AB  - The existence of catechol estrogens in rat brains was clarified using liquid
      chromatography-atmospheric pressure chemical ionization-ion trap-mass
      spectrometry-mass spectrometry (LC-APCI-MS2). The catechol estrogens were
      extracted in the presence of ascorbic acid and then derivatized to acetates with
      acetic anhydride and pyridine. After a successive purification with silica gel
      mini-column chromatography, reversed-phase solid-phase extraction and preparative
      HPLC, the obtained fractions containing the catechol estrogen acetates were
      subjected to LC-APCI-MS2. 2-Hydroxyestrone, 2-hydroxyestradiol and their 4
      hydroxy isomers were identified as acetates by comparison with authentic samples
      based on their chromatographic behavior and mass spectral data. The
      derivatization to acetate was useful for the treatment of labile catechol
      estrogens.

PMID- 10885056
TI  - A novel ethacrynic acid sensor based on a lanthanide porphyrin complex in a PVC
      matrix.
AB  - Lanthanide porphyrin complexes synthesized by a solid state method were used to
      prepare a novel ethacrynic acid (EA) sensor. The sensor, based on pentane-2,4
      dionato(meso-tetraphenylporphinato)terbium [TbTPP(acac)] with an optimized
      membrane composition, exhibits a Nernstian response to EA- ion in the
      concentration range 7.4 x 10(-6)-1.0 x 10(-1) mol l-1 with a pH range from 3.2 to
      6.8 and a fast response time of 30 s. The electrode shows improved selectivity
      towards EA- ion with respect to common co-existing ions compared with the
      previously reported EA sensor. As electroactive materials, lanthanide porphyrin
      complexes show better potentiometric response characteristics than copper
      porphyrin complexes. The effect of solvent mediators and lipophilic ion additives
      was studied and the experimental conditions were optimized. The electrode was
      applied to the determination of EA in human urine samples with satisfactory
      results.

PMID- 10885057
TI  - Flow injection spectroscopic analysis of model drugs using on-line UV-diode
      array, FT-infrared and 1H-nuclear magnetic resonance spectroscopy and time-of
      flight mass spectrometry.
AB  - A prototype flow injection analysis (FIA) system for the characterisation of
      compounds via a combination of diode array UV, 1H NMR, FT-IR spectroscopy and
      time-of-flight (TOF) mass spectrometry has been investigated using a number of
      pharmaceuticals and related compounds as model compounds. This combination of
      spectrometers allowed the on-flow collection of UV, 1H NMR, IR and mass spectra
      together with atomic composition data, enabling almost complete structural
      characterisation to be performed. Practical detection limits with the current
      system were in the region of 50 micrograms, however, the use of state of the art
      spectrometers would result in a significant reduction in the amount of material
      required.

PMID- 10885058
TI  - Potentiality of proton nuclear magnetic resonance and multivariate calibration
      methods for the determination of dermatan sulfate contamination in heparin
      samples.
AB  - A 1H NMR method for the quantification of dermatan sulfate impurities in heparin
      industrial samples is proposed. The method is based on the analysis of 1H NMR
      spectral data by multivariate calibration. The 1H NMR spectra of heparin and
      dermatan sulfate standards showed characteristic profiles. Thus, differences in
      the methyl peaks of acetamido groups of heparin and dermatan sulfate were greatly
      advantageous for the analysis. Other hydrogens of the sugar ring were also
      relevant in this study. Thus, the determination of dermatan sulfate by
      multivariate calibration depended on all these differences. Partial least squares
      regression (PLS) was chosen as the calibration method. In addition, a data
      standardization procedure was developed in order that 1H NMR spectra registered
      with different instruments operating under different measurement conditions were
      comparable. The quantification of dermatan sulfate in the samples was
      satisfactory, with an overall prediction error of 6%.

PMID- 10885059
TI  - Use of perchloric acid as a reaction medium for speciation of arsenic by hydride
      generation-atomic absorption spectrometry.
AB  - Simple and inexpensive methods for the speciation of arsenite, arsenate,
      monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in environmental
      water samples were developed. In these methods a hydride generation-atomic
      absorption spectrometry (HG-AAS) technique was employed and perchloric acid (as a
      reaction medium), L-cysteine (as a pre-reducing agent for a certain contact time
      between its addition and analysis) and sodium tetrahydroborate(III) (NaBH4, as a
      reducing agent) were used. The use of L-cysteine greatly enhances the absorption
      signals of all four arsenic species at low acid concentration (0.001-0.04 M). The
      methods developed for the determination of total arsenic and total inorganic
      arsenic and speciation of the four arsenic species in environmental water samples
      are as follows. (i) DMA: 0.005 M acid and 0.04% NaBH4 in the absence of L
      cysteine. DMA can also be speciated in the presence of L-cysteine as follows: 2 M
      acid, 2.5% L-cysteine after a contact time of approximately 5 min and 0.6% NaBH4.
      (ii) As(III): 5 M acid and 0.08% NaBH4 in the absence of L-cysteine. (iii) Total
      inorganic arsenic (As(III) + As(V)]: 8 M acid and 0.6% NaBH4 in the absence of L
      cysteine. (iv) Total arsenic: 0.01 M acid, 5% L-cysteine after a contact time of
      5 min and 2% NaBH4. (v) MMA: 8 M acid, 3% L-cysteine after a contact time of 50
      min and 0.6% NaBH4. (vi) As(V): by difference. Detection limits and recoveries of
      added spikes for all analyses were found to be 0.5-1.7 ppb and 90-112%
      respectively.

PMID- 10885060
TI  - Bio-inorganic speciation analysis by hyphenated techniques.

PMID- 10885062
TI  - Ultrasensitive, direct detection of a specific DNA sequence of Bacillus anthracis
      in solution.
AB  - A very fast and ultrasensitive method has been developed for the detection and
      quantitation of specific nucleic and sequences of bacterial origin in solution.
      The method is based on a two-color, single fluorescent molecule detection
      technique developed in our laboratory. The technique was applied to the detection
      of Bacillus anthracis DNA in solution.

PMID- 10885061
TI  - Renewable pencil electrodes for highly sensitive stripping potentiometric
      measurements of DNA and RNA.
AB  - Renewable graphite pencil electrodes are demonstrated to be excellent materials
      for adsorptive stripping measurements of trace nucleic acids. While displaying an
      attractive stripping performance, comparable to that of conventional carbon paste
      electrodes, the pencil electrode offers a convenient (mechanical) renewal, with
      each stripping potentiogram recorded at a fresh surface. Various pencil lead
      materials and lengths have been examined and experimental variables of the
      pretreatment and measurement procedures have been explored and optimized. The
      extremely low detection limits (e.g., 3 micrograms l-1 tRNA with 10 min
      accumulation) are coupled to a good surface-to-surface reproducibility (RSD of
      6.4% for 14 repetitive measurements of 1 mg l-1 ssDNA).

PMID- 10885063
TI  - Nanobiotechnology and its role in the development of new analytical devices.
AB  - Physical methods of molecule observation and manipulation will prove useful, not
      only as research tools for investigating biomolecular structure and behavior, but
      also for the creation of nanostructures. Supramolecular and self-assembling
      structures are able to generate nanostructures, with many such systems being of
      biological origin. They form the interface between nanotechnology and
      biotechnology. Whereas biotechnological processes usually involve populations of
      cells or molecules, nanotechnological methods operate at the level of individual
      molecule manipulation. This article considers what advances have been made
      through cross-fertilisation between nanotechnology and biotechnology to develop
      for the next millennium new analytical tools at the microscale, using
      nanostructures as the sensitive part and with the ability to detect individual
      molecules.

PMID- 10885065
TI  - Reagentless enzyme electrode based on phenothiazine mediation of horseradish
      peroxidase for subnanomolar hydrogen peroxide determination.
AB  - The development and characterization of a highly sensitive enzyme immobilized
      carbon based electrode for the determination of subnanomolar concentrations of
      hydrogen peroxide in aqueous samples is described. The biosensor consists of
      horseradish peroxidase (HRP) immobilized in solid carbon paste along with a
      suitable redox mediator. The latter allows the acceleration of the
      electroreduction of HRP in the presence of hydrogen peroxide. Several
      phenothiazines as mediators are investigated in a comparative manner and with
      respect to dimethylferrocene using cyclic voltammetry and amperometry.
      Insolubilization of the HRP in the solid carbon paste is achieved by cross
      linking the enzyme with glutaraldehyde and bovine serum albumin. Several
      experimental parameters such as pH, mediator and enzyme content are considered.
      The hydrogen peroxide determination is better carried out in 0.1 M acetate
      buffer, pH 4.5, by amperometry at an applied potential of 0.0 V versus Ag/AgCl, 3
      M NaCl concentration and by using the phenothiazine base as redox mediator. The
      biosensor response is linear over the concentration range 2 nM-10 microM with a
      detection limit of 1 nM. The linear range of the hydrogen peroxide response
      without a mediator in the biosensor is found between 2 and 40 microM. The
      biosensor can be used for more than 180 measurements. Additional modification of
      the electrode by incorporation of Nafion SAC-13 microparticles in the solid
      carbon paste allows detection of concentrations of hydrogen peroxide as low as
      0.1 nM.

PMID- 10885064
TI  - Selenium speciation in enriched and natural samples by HPLC-ICP-MS and HPLC-ESI
      MS with perfluorinated carboxylic acid ion-pairing agents.
AB  - Selenium-enriched plants, such as hyperaccumulative phytoremediation plants
      (Astragalus praleongus, 517 micrograms g-1 Se, and Brassica juncea, 138
      micrograms g-1 Se in dry sample), yeast (1200, 1922 and 2100, micrograms g-1 Se
      in dry sample), ramp (Allium tricoccum, 48, 77, 230, 252, 405 and 524 micrograms
      g-1 Se in dry sample), onion (Allium cepa, 96 and 140 micrograms g-1 Se in dry
      sample) and garlic (Allium sativum, 68, 112, 135, 296, 1355 micrograms g-1 Se in
      dry sample) were analyzed by HPLC-ICP-MS for their selenium content and
      speciation after hot water and enzymatic extractions. Reference samples with
      natural selenium levels, such as onion and garlic controls, cooking garlic
      powder, baking yeast powder and a commercial garlic supplement were also
      analyzed. Selected samples were also examined by HPLC-electrospray ionization
      (ESI)-MS. HPLC was mostly carried out with 0.1% heptafluorobutanoic acid (HFBA)
      as ion-pairing agent in 1 + 99 v/v methanol-water solution, but 0.1%
      trifluoroacetic acid (TFA) in 1 + 99 v/v methanol-water solution was also
      utilized to permit chromatography for compounds that did not elute with HFBA.
      More than 75% of the total eluting selenium compounds, based upon element
      specific detection, were identified from retention time data and standard spiking
      experiments, and between 60 and 85% of compounds were identified by MS, with up
      to 25% of the total eluting molecular selenium species being unidentified as yet.
      Limits of quantification (LOQ, defined as the concentration giving an S/N of 10)
      for HPLC-ICP-MS were in the range 2-50 ng mL-1 Se in the injected extracts for
      the selenium-enriched samples and 2-10 ng mL-1 Se for the natural selenium level
      samples. LOQ values for HPLC-ESI-MS were ca. 100 times higher than those measured
      by HPLC-ICP-MS.

PMID- 10885066
TI  - Determination of morphine, oripavine and pseudomorphine using capillary
      electrophoresis with acidic potassium permanganate chemiluminescence detection.
AB  - A simple and robust capillary electrophoresis chemiluminescence detection system
      for the determination of morphine, oripavine and pseudomorphine is described,
      based upon the reaction of these analytes with acidic potassium permanganate in
      the presence of sodium polyphosphate. The reagent solution was contained in a
      quartz detection cell which also held both the capillary and the anode. The
      resultant chemiluminescence was monitored directly using a photomultiplier tube
      mounted flush against the base of the detection cell. To ensure that no migration
      of the permanganate anion occurred, the anode was placed at the detector end
      whilst the electroosmotic flow was reversed by the addition of hexadimethrine
      bromide (0.001% m/v) to the electrolyte. The three analytes were separated
      counter to the electroosmotic flow via their interaction with alpha-cyclodextrin.
      The methodology realised detection limits (3 x S/N) of 2.5 x 10(-7) M for both
      morphine and oripavine and 5 x 10(-7) M for pseudomorphine. The relative standard
      deviations of the migration times and the peak heights for the three analytes
      ranged from 0.6 up to 0.8% and from 1.5 up to 2.1%, respectively.

PMID- 10885067
TI  - Microdialysis sampling with on-line microbore HPLC for the determination of
      tirapazamine and its reduced metabolites in rats.
AB  - An on-line microdialysis microbore HPLC method is described for the determination
      of the bioreductive anti-tumor agent, tirapazamine (3-amino-1,2,4-benzotriazine
      1,4-di-N-oxide, SR4233, WIN59075, Tirazone, TPZ) and its two major reduced
      metabolites, 3-amino-1,2,4-benzotriazine-1-N-oxide (SR4317) and 3-amino-1,2,4
      benzotriazine (SR4330). Detection limits of 0.003 microM, 0.005 microM and 0.007
      microM were obtained for tirapazamine, SR4317 and SR4330, respectively. Linear
      ranges of 0.011-20 microM, 0.017-20 microM and 0.025-20 microM for tirapazamine,
      SR4317 and SR4330 permitted quantitative analysis of all three compounds in
      microdialysis samples. Typical intra-day reproducibilities (n = 7) of 4.1%
      (tirapazamine), 6.6% (SR4317), 9.9% (SR4317), and 1.8% (tirapazamine), 2.4%
      (SR4317) and 2.6% (SR4330) were obtained at the 0.12 microM and 1.2 microM
      levels, respectively. Inter-day reproducibilities (n = 5) of 3.4% (tirapazamine),
      1.8% (SR4317), 4.5% (SR4330) and 2.5% (tirapazamine), 2.5% (SR4317) and 1.7%
      (SR4330) were obtained at the 0.12 microM and 1.2 microM levels, respectively.
      The use of an on-line microdialysis HPLC system, permitted the determination of
      tirapazamine, SR4317 and SR4330 in blood and muscle tissue of rats with a high
      temporal resolution of sampling. The pharmacokinetics of tirapazamine and its
      metabolites were studied in the muscle and blood of rats previously administered
      an intraperitoneal dose of tirapazamine.

PMID- 10885068
TI  - Investigation of amine and polyol functionality in extracts of polyurethane wound
      management dressings using MALDI-MS.
AB  - Polyurethane (PU) foams used in wound management are produced by a reaction
      between aromatic diisocyanates and polyether polyols. There is concern that
      residues of these starting materials, which may contain aromatic amine
      functionality, may leach from the finished polymer during in vivo applications.
      Furthermore, oligomers and additives may be leached from the PU system after the
      polymerization process is complete. Finished polymers have, therefore, been
      extracted with a range of solvents, such as water, diethyl ether and dilute HCl.
      The extracts were subjected to MALDI-MS (matrix-assisted laser desorption
      ionization mass spectrometry) analysis in an attempt to determine the amine and
      polyol functionality. Direct MALDI-MS analysis of the wound dressing extracts
      indicated the presence of components based on the polyols [corrected] used in the
      formulation of the foam. The spacing between the peaks identified the base
      monomer used in the polyol. MALDI-MS analysis of the fluorescamine derivatives of
      model amine compounds has demonstrated the anticipated increase in mass (278 for
      monoamines and 278 and 556 for diamines). Similar results were obtained from the
      derivatization of model polyols with phenyl isocyanate, where the mass shift (n x
      119) was a direct measure of the number of active hydroxyl groups. Fluorescamine
      labelling of PU foams shows the colour change which could be [corrected]
      indicative of the presence of an amine, but the subsequent MALDI-MS analysis was
      unable to demonstrate the anticipated increase in mass.

PMID- 10885069
TI  - MALDI-MS and colorimetric analysis of diisocyanate and polyol migrants from model
      polyurethane adhesives used in food packaging.
AB  - The identification of the migrants, into food simulants, from a series of
      polyurethane adhesives used in the manufacture of plastic film laminates for use
      in common food packaging is described. Commercial materials, based on four
      different model adhesive systems, were prepared by an industrial collaborator.
      The MALDI-MS fingerprint patterns of the three polyether and one polyester polyol
      components of these adhesives were obtained for reference purposes. The decrease
      in the level of diisocyanate as a migrant versus time after lamination was
      confirmed by colorimetric measurements. The migration of the standard polyol
      samples through polyethylene pouches into water at 70 degrees C has been
      demonstrated and also the attenuation effect for different polyols. Cured
      laminates in the form of pouches were used to carry out the migration experiments
      into distilled water, inside the pouch, at 70 degrees C over a period of 2 h.
      Comparison of the migration results from the food packaging laminates with those
      from the polyethylene film confirmed the migration of unreacted polyol components
      for the polyether-based systems. Cyclic oligomers from the polyol starting
      materials were identified as the migrants from the polyester-based adhesive.

PMID- 10885070
TI  - Rapid analysis of illicit drugs by mass spectrometry: results from seizures in
      Ireland.
AB  - A gas chromatographic procedure with mass spectrometric detection (GC-MS) was
      established to determine the principal amphetamines,
      methylenedioxymethamphetamine (MDMA), methylenedioxyethamphetamine (MDEA) and
      methylenedioxyamphetamine (MDA), cocaine and pharmacologically active impurities
      in 'ecstasy' tablets. The procedure was developed and optimised by combining the
      individual methods for the various drugs of abuse available in the literature
      into a single GC-MS run. New variants of the main drugs which may appear on the
      drug scene were also detected, including N-methyl-1-phenylethylamine, a member of
      a new series of illicit drugs. The method is rapid and has good sensitivity and
      reproducibility.

PMID- 10885071
TI  - Models for estimating the non-specific toxicity of organic compounds in short
      term bioassays.
AB  - The solvation parameter model is used to construct equations for the estimation
      of the non-specific toxicity of neutral organic compounds to five organisms used
      for short-term toxicity testing. For the bacteria Vibrio fischeri (Microtox test)
      and Pseudomonas putida, the protozoan Tetrahymena pyriformis (Tetratox test), the
      green alga Scendesmus quadricauda and the brine shrimp Artemia salina, the main
      factors resulting in increased non-specific toxicity are size (dominantly) and
      lone-pair electron interactions, with hydrogen-bond basicity the most important
      solute property reducing toxicity. Species differences in relative non-specific
      toxicity are largely related to differences in cohesion and hydrogen-bond acidity
      of the biomembranes. The models for non-specific toxicity are proposed as an
      alternative to the octanol-water distribution constant for the determination of
      baseline toxicity. Failure of the octanol-water distribution constant to model
      non-specific toxicity is quantitatively explained by its inability to adequately
      characterize the sorption properties of the biomembranes for compounds with
      varied properties.

PMID- 10885072
TI  - An electrochemiluminescence-based fibre optic biosensor for choline flow
      injection analysis.
AB  - A fibre optic biosensor based on luminol electrochemiluminescence (ECL)
      integrated in a flow injection analysis (FIA) system was developed for the
      detection of choline. The electrochemiluminescence of luminol was generated by a
      glassy carbon electrode polarised at +425 mV vs. a platinum pseudo-reference
      electrode. Choline oxidase (Chx) was immobilised either covalently on polyamide
      (ABC type) or on UltraBind preactivated membranes, or by physical entrapment in a
      photo-cross-linkable poly(vinyl alcohol) polymer (PVA-SbQ) alone or after
      absorption on a weak anion exchanger, DEAE (diethylaminoethyl) Sepharose. The
      optimisation of the reaction conditions and physicochemical parameters
      influencing the FIA biosensor response demonstrated that the choline biosensor
      exhibited the best performances in a 30 mM veronal buffer containing 30 mM KCl
      and 1.5 mM MgCl2, at pH 9. The use of a 0.5 ml min-1 flow rate enabled the
      measurement of choline by the membrane-based ECL biosensors in 8 or 5 min, with
      ABC or UltraBind membranes, respectively, whereas the measurement required only 3
      min with the DEAE-PVA system. For comparison, the detection of choline was
      performed with Chx immobilised using the four different supports. The best
      performances were obtained with the DEAE-PVA-Chx sensing layer, which allowed a
      detection limit of 10 pmol, whereas with the ABC, the UltraBind and the PVA
      systems, the detection limits were 300 pmol, 75 pmol and 220 pmol, respectively.
      The DEAE-based system also exhibited a good operational stability since 160
      repeated measurements of 3 nmol of choline could be performed with an RSD of 4.5%
      whereas the stability under the best conditions was 45 assays with the other
      supports.

PMID- 10885073
TI  - A novel electrochemical microsensor for the determination of NO and its
      application to the study of the NO donor S-nitrosoglutathione.
AB  - A novel electrochemical microsensor for the determination of NO based on an
      electropolymerized film of tetraaminophthalocyaninecopper [Cu(TAPc)] was
      prepared. Its response to NO and its application to the study of an NO donor (S
      nitrosoglutathione; GSNO) are also described. The microsensor exhibited an
      electrocatalytic effect on NO oxidation and showed a low detection limit, high
      sensitivity and selectivity for NO determination. The oxidation current (measured
      by differential pulse amperometry) was linear for NO concentrations ranging from
      6.2 x 10(-9) to 3.0 x 10(-5) mol L-1 with a calculated detection limit of 4.0 x
      10(-9) mol L-1 (S/N = 3) and a linear coefficient of 0.9984. Some endogenous
      electroactive substances in biological tissues, such as dopamine, 5
      hydroxytryptamine and nitrite, at concentrations higher than those in biological
      systems did not interfere with NO determination. The sensor shows promise for the
      possible in vivo determination of NO. Using the microsensor, the NO release from
      the NO donor (GSNO) was successfully monitored. This work sets a foundation for
      the study of the pharmacology and the biological effects in vivo of S
      nitrosothiols.

PMID- 10885074
TI  - Determination of rare earth elements in human blood serum by inductively coupled
      plasma mass spectrometry after chelating resin preconcentration.
AB  - The determination of all rare earth elements (REEs) in human blood serum by
      inductively coupled plasma mass spectrometry (ICP-MS) was performed with the aid
      of chelating resin (Chelex 100) preconcentration after acid digestion with HNO3
      and HClO4. When chelating resin preconcentration was carried out at room
      temperature, the recoveries of heavy REEs were lower than those of light REEs
      because of their stable complex formation with residual organic compounds
      remaining in the digested serum solution. These problems were overcome by heating
      the solution at 80 degrees C during the chelating resin preconcentration process.
      As a result, the recoveries for all REEs were improved to 92-102% in the case of
      a concentration factor of 4, where the analytical detection limits for REEs were
      below 0.2 x 10(-12) g ml-1. Consequently, all REEs in individual human blood sera
      collected from five healthy volunteers could be determined by ICP-MS with good
      precision. The concentrations of REEs in human blood serum were extremely low, in
      the range from ca. 1 x 10(-12) g ml-1 of Eu to ca. 230 x 10(-12) g ml-1 of Ce.

PMID- 10885076
TI  - Direct detection of large fat-soluble biomolecules in solution using membrane
      inlet mass spectrometry and desorption chemical ionization.
AB  - This paper presents the first membrane inlet mass spectrometry system capable of
      detecting large biomolecules, such as testosterone (M(r) 288), testosterone
      acetate (M(r) 330) and alpha-tocopherol (M(r) 430, vitamin E). The result was
      obtained using a home-made chemical ionization ion source with a thermostated
      tubular silicone membrane mounted right in the centre of a methane CI plasma. The
      liquid sample was flushed through the inside of the membrane for a period of 20
      25 min, where the analyte diffused into the membrane. Following this trapping
      period the analyte was released from the membrane into the mass spectrometer by
      the combined action of heat radiation from the filament and charge transfer from
      the chemical ionization plasma. As a result of this stimulated desorption a good
      desorption peak was obtained as the analyte vaporized out of the membrane.
      Retinol (M(r) 286, vitamin A), cholecalciferol (M(r) 384, vitamin D3) and
      cholesterol (M(r) 386) were also detected. However, these compounds (all
      containing a long hydrocarbon chain and being aliphatic alcohols) did not give a
      protonated molecule. They gave a series of cluster ions with the dominant located
      20 mass units below the molecular ion. The detection limits of the new desorption
      chemical ionization MIMS technique were at low or sub-micromolar concentrations
      (high ppb levels) and the reproducibility was within 20%, when the area of the
      desorption peak was used for quantitation.

PMID- 10885075
TI  - Speciation of protein-binding zinc and copper in human blood serum by chelating
      resin pre-treatment and inductively coupled plasma mass spectrometry.
AB  - A method for the speciation of zinc and copper binding with proteins in human
      serum was explored by chelating resin (Chelex-100) pre-treatment and inductively
      coupled plasma mass spectrometry (ICP-MS). It was shown by a SEC (size-exclusion
      chromatography)-ICP-MS system that albumin-zinc and albumin-copper (loosely-bound
      species) could be selectively removed from serum by adsorption on the Chelex-100
      resin after the chelating resin pre-treatment, while alpha 2-macroglobulin-zinc
      and ceruloplasmin-copper (firmly-bound species) remained in the serum. The zinc
      and copper bound with alpha 2-macroglobulin and ceruloplasmin, respectively, were
      then determined by ICP-MS after batch treatment of the serum samples with the
      Chelex-100 resin. In addition, the total concentrations of zinc and copper were
      also determined by ICP-MS after a 20-fold dilution with 0.1 M HNO3. The albumin
      zinc and -copper were estimated as the differences between the concentrations of
      total and firmly-bound species. The present batch pre-treatment method was
      applied to the speciation analysis of zinc and copper binding with proteins in
      sera donated from 25 healthy volunteers as well as from a pregnant woman and a
      myelodysplastic syndrome patient. The observed concentrations of alpha 2
      macroglobulin-zinc and ceruloplasmin-copper were in the ranges 109-202 ng ml-1
      (12.4-31.3% of total zinc) and 513-880 ng ml-1 (90.6-99.7% of total copper),
      respectively. The present method is simple (only addition of the chelating resin
      and centrifugation is required) and reproducible (average RSD = 2% for alpha 2
      macroglobulin-zinc and 1% for ceruloplasmin-copper in intra-assay measurements,
      and 5% for alpha 2-macroglobulin-zinc and 4% for ceruloplasmin-copper in inter
      assay measurements), and there is less risk of contamination during separation.

PMID- 10885077
TI  - Determination of cyclamate in low-calorie foods by high-performance liquid
      chromatography with indirect visible photometry.
AB  - A rapid and simple method using reversed-phase high-performance liquid
      chromatography combined with indirect visible photometry at 433 nm was developed
      to determine cyclamate in some food samples. Cyclamate was not detected in these
      chosen samples as its use is banned in Hong Kong. Cyclamate can easily be
      detected in spiked samples using a mobile phase consisting of 30 mumol dm-3
      Methyl Red and 0.02 mol dm-3 phosphate buffer (pH 7.0)-methanol in a volume ratio
      of 3:2. The column temperature was set at 23 degrees C. The detection limit was
      0.14 mmol dm-3 and the relative standard deviation of the peak area response was
      0.58% for a solution containing 5.0 mmol dm-3 of cyclamate (n = 8). This method
      was successfully applied to the analysis of eight spiked food samples and the
      cyclamate recoveries for these samples ranged from 93 to 99%.

PMID- 10885078
TI  - Kawasaki disease--a diagnostic challenge.

PMID- 10885079
TI  - Depression in pregnant and postnatal women: an evidence-based approach to
      treatment in primary care.

PMID- 10885080
TI  - A qualitative investigation of women's perceptions of premenstrual syndrome:
      implications for general practitioners.
AB  - BACKGROUND: Many women consult general practitioners each year, seeking treatment
      for premenstrual syndrome. This qualitative study presents evidence of women's
      own perceptions of this problem, which may assist in the provision of
      individualized health care. AIM: To explore women's constructions of premenstrual
      syndrome using grounded analysis. METHOD: A qualitative, semi-structured
      interview study carried out in Northern Ireland. Thirteen women were interviewed
      individually. Thereafter, 33 women participated in group discussions. Five health
      visitors then commented individually on the findings. RESULTS: Seven themes
      emerged from the analysis. These themes suggested that women tend to view the
      menstrual cycle holistically and that premenstrual syndrome is regarded as
      debilitating by only a small minority of women. Participants indicated an
      awareness of the intra- and inter-personal variability of menstrual experience.
      They were ambivalent about menstruation, viewing it as natural but, at the same
      time, unnatural in terms of day-to-day existence. Talking to other women served
      two functions, first by providing a yardstick against which to evaluate their own
      experiences, and secondly by providing support and advice. In contrast, women
      tended to talk about menstruation only to selected men, mainly partners,
      primarily in the interests of educating them. Women viewed menstruation as
      potentially disempowering by virtue of its uncontrollability, and felt that both
      a positive attitude and the use of a range of remedies were important for women
      wishing to become empowered with respect to this aspect of their lives.
      CONCLUSIONS: Women's own constructions of premenstrual syndrome differ markedly
      from those as presented in medical textbooks and research literature: secondary
      sources that have significantly impacted upon general practitioners' attitudes
      towards this condition. The provision of a range of treatment options, including
      support groups, is suggested, on the basis of evidence gathered using qualitative
      methods, as likely to be viewed by women as more appropriate than offering
      treatment based on the evidence provided by traditional randomized controlled
      trials.

PMID- 10885081
TI  - Patients with irritable bowel syndrome: health status and use of health care
      services.
AB  - BACKGROUND: The reason for consulting a physician is more related to illness
      behaviour than to the severity of complaints. Yet, little is known about the
      course of complaints, the health care seeking behaviour, and psychosocial factors
      influencing these items in patients with irritable bowel syndrome (IBS) attending
      the general practitioner (GP). AIM: To study health status, lifestyle, and use of
      health care services of patients with IBS in order to indicate problem areas
      accessible for intervention strategies. METHOD: Structured interviews of 53
      patients with IBS aged 15 years and older compared with a general population of
      12,975 in the same age range, all drawn from the Dutch National survey of
      Morbidity and Intervention in General Practice. RESULTS: Patients with IBS
      revealed a lower grade of education (P < 0.001), poorer health (P < 0.001), a
      higher mean complaint score (8.3 versus 4.0, P < 0.001), a higher score on the
      General Health Questionnaire (P < 0.001), a higher score on the biographic
      problem list (BIOPRO, 2.3 versus 1.4, P < 0.001), and more absence from work (32%
      versus 18% in two months, P < 0.01). Patients with IBS consulted the family
      physician (1.6 versus 0.8 in three months, P < 0.001), the physical therapist
      (30% versus 15% in one year, P < 0.001), and the alternative therapist (32%
      versus 15% in five years, P < 0.001) more often than those without. CONCLUSIONS:
      The study shows an excess of comorbidity, psychosocial problems, use of health
      care services, and absence owing to disease in patients with IBS. Special
      guidelines and training of GPs to apply a more integral approach may reduce the
      cost of health care and may lead to a more favourable course in patients with
      IBS.

PMID- 10885082
TI  - Supporting practice-based audit: a price to be paid for collecting data.
AB  - BACKGROUND: There has been considerable investment by health authorities in the
      funding of support staff whose job is to collect data for audit purposes. It is
      important to understand what costs are involved in such a data collection
      exercise. The cost advantages of using existing practice staff or externally
      funded staff are not known. AIM: To assess the cost of transposing data on
      workload to computer software for audit purposes and retrieving data on five
      chronic diseases from case records. METHOD: Four audit support staff monitored
      the time taken to collect specific data as part of a broad audit programme in 12
      training practices within one health board area in the West of Scotland in 1997.
      The time taken was used to estimate comparative costs for using a receptionist or
      practice nurse for carrying out a similar exercise. RESULTS: Average costs for
      collecting data per 1000 patients for waiting time, appointments, recall, and
      telephone audits were 5.24 Pounds for reception staff, 5.64 Pounds for audit
      support staff, and 9.68 Pounds for a practice nurse. The average cost for
      collecting data per patient with diabetes, asthma, epilepsy, hypertension, or
      rheumatoid arthritis was 1.48 Pounds for reception staff, 1.60 Pounds for audit
      support staff, and 2.74 Pounds for a practice nurse. CONCLUSIONS: The cost of
      collecting data varies considerably depending on which staff are chosen for the
      purpose. Practices should consider carefully how best to collect data for audit
      in terms of cost.

PMID- 10885083
TI  - What do patients want from doctors? Content analysis of written patient agendas
      for the consultation.
AB  - BACKGROUND: Although much has been written about what patients want when they
      contact their general practitioner (GP), there are no published data from large
      cohort studies of what patients expect. AIM: To describe the expectations of a
      large group of patients who consulted with their GPs. METHOD: A GP and a social
      sciences graduate carried out a content analysis of written agenda forms
      completed by 819 patients who consulted 46 randomly selected GPs. Inter- and
      intra-rater reliabilities were confirmed. RESULTS: A total of 756 (92%) agenda
      forms were returned. Inter-rater reliability was satisfactory (kappa > 0.6 for
      all but two main themes). Almost all patients had requests they wished to make of
      their doctor, 60% had their own ideas about what was wrong, and 38% had
      considered explanations about why they were unwell. Forty-two per cent and 24% of
      patients had consulted because they had reached the limit of their anxiety or
      tolerance respectively. Seven per cent, 4%, and 2% had comments, which were
      usually negative, to make about previous management, communication with doctors,
      or time in the consultation. CONCLUSION: These data demonstrate that most
      patients come to the consultation with a particular agenda. Failure to address
      this agenda is likely to adversely affect the outcome of many consultations.

PMID- 10885084
TI  - The health of their nation: how would citizens develop England's health strategy?
AB  - BACKGROUND: England's first health strategy, The Health of the Nation, was
      formulated without systematic input from the citizens whose health it targeted.
      Several studies indicate that citizens, when asked to prioritize services, rank
      interventions for acute and life-threatening conditions highest. But how they
      view and what they want in the areas of prevention, public health, or care for
      the chronically and mentally ill is not known. AIM: To explore citizens'
      attitudes towards England's health strategy as set out in The Health of the
      Nation and to elicit their ideas for developing it further. METHOD: The study was
      conducted in four general practices and a secondary school in southwest England.
      The design was a qualitative analysis of testimony from 24 audiotaped focus
      groups. Twenty-three groups were drawn from lists of National Health Service
      registered patients, stratified by The Health of the Nation target category, and
      one group was drawn from 13 to 15 year-old girls at a mixed secondary school. In
      all, 173 citizens took part in the 24 focus group meetings. RESULTS: In group
      discussions, these citizens demonstrated an understanding of The Health of the
      Nation strategy, which enabled them to form views and develop relevant arguments.
      They produced 26 specific ideas for developing the strategy across its five key
      areas. There was congruence with the action plans of a national expert group
      convened by the Department of Health and charged with reviewing the strategy's
      progress. The focus groups went beyond the experts' proposals, with further
      practical ideas to achieve The Health of the Nation targets. CONCLUSION: Citizens
      in this study contributed a broad range of relevant, appropriate, and innovative
      ideas on how to develop health strategy. The use of focus groups to achieve this
      is practical and efficient.

PMID- 10885085
TI  - Who is targeted for lifestyle advice? A cross-sectional survey in two general
      practices.
AB  - BACKGROUND: Recent health promotion guidelines reimbursed primary health care
      teams for targeting lifestyle advice to patients at risk of cardiovascular
      disease. However, it is unclear whether primary health care teams do target
      advice, who is targeted, and whether the advice is acted upon. AIM: To assess
      which factors predict the targeting and recall of lifestyle advice. METHOD: A
      total of 370 patients with, and 192 without, a computer record of risk factors
      for cardiovascular disease (hypertension, diabetes, ischaemic heart
      disease/myocardial infarction/angina, a body mass index > or = 30) from two
      contrasting Wessex practices were sent a postal questionnaire about medical
      conditions, recall of lifestyle advice, current lifestyle, and their perceptions
      about the health of their lifestyle. RESULTS: Seventy-seven per cent of patients
      responded. There was good agreement between listed risk factors and patients
      reporting a risk factor (kappa = 0.60), which was similar for both sexes and
      better in older age groups. Recall of lifestyle advice was not significantly
      affected by practice, but was more likely in patients with listed risk factors
      (adjusted odds ratio [OR] = 4.62, 95% confidence intervals [CI] = 2.89-7.37) and
      in men (OR = 1.64, 95% CI = 1.07-2.52), and less likely in older age groups (age
      < or = 64 years = 1.00; 65-74 years = 0.47, 95% CI = 0.27-0.81; 75+ years = 0.34,
      95% CI = 0.20-0.60). Of patients with listed risk factors, 27% could not recall
      having received any advice, and recall varied with medical condition. Only 40% of
      patients with reported high blood pressure recalled being given advice about
      salt. Those who recalled advice were more likely to report a healthier current
      lifestyle. Of those with unhealthy lifestyles, 30-50% were unaware that their
      lifestyle was unhealthy. CONCLUSION: Lifestyle advice is not recalled for some
      important risk factors, and some patients are unaware of their unhealthy
      lifestyle. Although advice is being preferentially targeted to those with risk
      factors, women and older patients recall advice less. Research is needed to
      assess the cost-effectiveness of advice for both sexes and different ages.

PMID- 10885086
TI  - The presentation and management of breast symptoms in general practice in South
      Wales. The BRIDGE Study Group.
AB  - Although there is increasing interest in the primary care management of breast
      disorders, there are few data on their presentation and management. This study
      recorded presentation rates of breast symptoms in 34 general practices in South
      Wales. These ranged from 1.9 to 14.8 patients per GP per year (median = 6.5):
      46.4% with breast lump, 28.2% with breast pain, 16.2% with lumpiness and 5.5%
      with nipple discharge. Fifty-five per cent of all patients were referred,
      substantially more than previously recorded. Some referrals for breast disease
      may be 'inappropriate' according to current management guidelines.

PMID- 10885087
TI  - Do people attending a same day testing clinic discuss their need for a HIV test
      with their GP?
AB  - In the United Kingdom, people with HIV infection present with advanced disease
      and general practitioners (GPs) are currently an underused resource for HIV
      testing. We describe the reasons for using an open-access clinic rather than
      primary care for testing for HIV. People attending the clinic were asked to
      complete a questionnaire asking about GP registration, access, and whether HIV
      testing was discussed in primary care. Despite access to GPs, HIV testing in
      primary care was rarely discussed. If HIV testing is to move to a general
      practice setting, GPs could address the issues, such as the recording of
      sensitive information in notes, future life insurance, and confidentiality, which
      this report identifies as the main barriers for using primary care.

PMID- 10885088
TI  - Sexual lifestyle of women attending inner-city general practices for cervical
      smears.
AB  - Despite high prevalences of sexually transmitted infections, little is known
      about the sexual lifestyles of women attending inner-city general practices.
      Responses from a 1996 questionnaire showed that age at first intercourse and
      numbers of sexual partners were similar to the national survey five years
      earlier. However, only 49% of women reporting > or = 2 sexual partners in the
      past year said their partner had used a condom at the last sexual intercourse.

PMID- 10885089
TI  - How to provide for the primary health care needs of homeless people: what do
      homeless people in Leicester think?
AB  - The best means of improving access to primary health care for homeless people
      remains controversial, but the debate may be informed by the opinions of homeless
      people. A questionnaire asked users of a homeless drop-in centre to choose
      between the options of facilitated access to mainstream primary health care or
      special provision for homeless people. While both models of care were endorsed,
      84% of homeless people preferred a special homeless service.

PMID- 10885090
TI  - Validity of susceptibility testing of uropathogenic bacteria in general practice.
AB  - Resistance of uropathogenic bacteria to antibiotics is an increasing problem in
      primary health care. The aim of this study was to evaluate antibacterial
      susceptibility testing of uropathogenic bacteria when performed in general
      practice. Urine specimens with a known quantity of typically uropathogenic
      bacteria were sent to 25 general practices. The predictive values of testing a
      bacterial strain as susceptible ranged from 0.89 (nitrofurantoin) to 1.00
      (sulphamethizole), and the predictive value of testing a bacterial strain as
      resistant ranged from 0.55 (trimethoprim) to 0.90 (nitrofurantoin). Interventions
      to improve the validity of susceptibility testing are desirable if the test
      should be incorporated in the diagnostic armamentarium in general practice.

PMID- 10885092
TI  - Recruitment and retention of general practitioners in the UK: what are the
      problems and solutions?
AB  - Recruitment and retention of general practitioners (GPs) has become an issue of
      major concern in recent years. However, much of the evidence is anecdotal and
      some commentators continue to question the scale of workforce problems. Hence,
      there is a need to establish a clear picture of those instabilities (i.e.
      imbalances between demand and supply) that do exist in the GP labour market in
      the UK. Based on a review of the published literature, we identify problems that
      stem from: (i) the changing social composition of the workforce and the fact that
      a large proportion of qualified GPs are significantly underutilized within
      traditional career structures; and (ii) the considerable differences in the
      ability of local areas to match labour demand and supply. We argue that one way
      to address these problems would be to encourage greater flexibility in a number
      of areas highlighted in the literature: (i) time commitment across the working
      day and week; (ii) long-term career paths; (iii) training and education; and (iv)
      remuneration and contract conditions. Overall, although the evidence suggests
      that the predicted 'crisis' has not yet occurred in the GP labour market as a
      whole, there is no room for lack of imagination in planning terms. Workforce
      planners continue to emphasize national changes to the medical school intake as
      the means to balance labour demand and supply between the specialities; however,
      better retention and deployment of existing GP labour would arguably produce more
      effective supply-side solutions. In this context, current policy and practice
      developments (e.g. Primary Care Groups and Primary Care Act Pilot Sites) offer a
      unique learning base upon which to move forward.

PMID- 10885091
TI  - Aloe vera: a systematic review of its clinical effectiveness.
AB  - BACKGROUND: The use of aloe vera is being promoted for a large variety of
      conditions. Often general practitioners seem to know less than their patients
      about its alleged benefits. AIM: To define the clinical effectiveness of aloe
      vera, a popular herbal remedy in the United Kingdom. METHOD: Four independent
      literature searches were conducted in MEDLINE, EMBASE, Biosis, and the Cochrane
      Library. Only controlled clinical trials (on any indication) were included. There
      were no restrictions on the language of publication. All trials were read by both
      authors and data were extracted in a standardized, pre-defined manner. RESULTS:
      Ten studies were located. They suggest that oral administration of aloe vera
      might be a useful adjunct for lowering blood glucose in diabetic patients as well
      as for reducing blood lipid levels in patients with hyperlipidaemia. Topical
      application of aloe vera is not an effective preventative for radiation-induced
      injuries. It might be effective for genital herpes and psoriasis. Whether it
      promotes wound healing is unclear. There are major caveats associated with all of
      these statements. CONCLUSION: Even though there are some promising results,
      clinical effectiveness of oral or topical aloe vera is not sufficiently defined
      at present.

PMID- 10885093
TI  - Repeat prescribing management.

PMID- 10885094
TI  - Nursing home residents: demands on GPs.

PMID- 10885095
TI  - Child health surveillance.

PMID- 10885096
TI  - Motivational consulting.

PMID- 10885097
TI  - Living wills.

PMID- 10885098
TI  - Reducing antimicrobial resistance in Spain.

PMID- 10885099
TI  - Data management in primary care.

PMID- 10885100
TI  - Simulated surgery.

PMID- 10885101
TI  - Food processing: a century of change.
AB  - In 1900, the population was beset with poverty, and infectious and deficiency
      diseases were common. The first half of the century was blighted by world wars,
      economic depression and post-war austerity. Nevertheless, a combination of
      enlightened social policy and the application of medical, nutritional and food
      science, resulted in substantial improvements in health, such that, by 1950, many
      hitherto common infectious diseases were under control, and the diet was
      generally nutritionally adequate. The second half of the century saw increasing
      economic prosperity, and unprecedented social and scientific advances. The impact
      on food processing was manifold: nascent technologies such as freezing and
      chilling were increasingly exploited, and the consumer became the major focus of
      a food industry that became more sophisticated, embracing automation,
      computerisation and new developments in, for example, drying, heat processing,
      controlled and modified atmosphere packaging, ingredients and quality assurance.
      By 1999, this had led to an industry which provided foods that were not only
      safe, nutritious and palatable, but which were also increasingly convenient and
      healthy.

PMID- 10885102
TI  - Nutrient requirements and optimisation of intakes.
AB  - In 1991, dietary reference values were published in the UK. These refer to
      nutrients and provide the basis for dietary advice. To complement this, practical
      food-based guidance on how to plan a healthy and balanced diet has been
      developed. Interest continues in how best to establish guidance which helps
      individuals modify their diets so as to better match the dietary targets
      established as a means of promoting health and avoiding disease. Furthermore, in
      recent years, interest has grown in the potential to optimise nutrition and so
      promote health and well-being, rather than just avoiding deficiency. This has
      been accompanied by an awareness that many foods, particularly plant foods,
      contain substances that may have health promoting properties but are not, as yet,
      regarded as conventional nutrients.

PMID- 10885103
TI  - Adverse reactions and intolerance to foods.
AB  - Food allergy is a form of adverse reaction to food in which the cause is an
      immunological response to a food. Common food triggers are eggs, cow's milk,
      peanuts and fish. Food allergy is mot common in young infants, most of whom grow
      out of the allergy by the age of 5 years. The exception is allergy to peanuts,
      which is life-long. The term food intolerance does not imply any specific type of
      mechanism, and is defined as a reproducible adverse reaction to a specific food
      or food ingredient. Mechanisms for food intolerance comprise immunological
      reactions (i.e. food allergy), enzyme defects, pharmacological effects, irritant
      effects, and toxic reactions. Despite the popular phobia of food additives and
      food processing, and the obsession for so-called natural foods, the greatest
      dangers come from naturally occurring foods and food ingredients.

PMID- 10885104
TI  - Animal health and food safety.
AB  - Foods of animal origin have an important role in a balanced diet and must be safe
      for human consumption. Equally important is the need for the food to be perceived
      as safe by the consumer. Safe food of animal origin must be free from animal
      pathogens that infect man and from contamination by residues. While intensive
      farming practices have been linked with the rise in foodborne illness in humans,
      it is interesting to note that the rise has continued even when there has been a
      shift to less intensive farm production systems. While the production of meat,
      milk and eggs, regardless of new technology or changes in production methods,
      cannot be expected to achieve zero bacterial risk, there is the need to reduce
      the risk and, where possible, eliminate it at the 'on the farm stage'. The
      current use of the terms 'farm-to-table', 'stable-to-table' and 'plough-to-plate'
      clearly identifies the farm as one part of the production chain which must be
      considered in terms of food safety.

PMID- 10885105
TI  - Genetically modified crops: methodology, benefits, regulation and public
      concerns.
AB  - The genetic modification of crop plants from the methodology involved in their
      production through to the current debate on their use in agriculture are
      reviewed. Techniques for plant transformation by Agrobacterium tumefaciens and
      particle bombardment, and for the selection of transgenic plants using marker
      genes are described. The benefits of currently available genetically modified
      (GM) crops in reducing waste and agrochemical use in agriculture, and the
      potential of the technology for further crop improvement in the future are
      discussed. The legal requirements for containment of novel GM crops and the roles
      of relevant regulatory bodies in ensuring that GM crops and food are safe are
      summarized. Some of the major concerns of the general public regarding GM crops
      and food: segregation of GM and non-GM crops and cross-pollination between GM
      crops and wild species, the use of antibiotic resistance marker genes, the
      prevention of new allergens being introduced in to the food chain and the
      relative safety of GM and non-GM foods are considered. Finally, the current
      debate on the use of GM crops in agriculture and the need for the government,
      scientists and industry to persevere with the technology in the face of
      widespread hostility is studied.

PMID- 10885107
TI  - Preservation: past, present and future.
AB  - Foods deteriorate in quality due to a wide range of reactions including some that
      are physical, some that are chemical, some enzymic and some microbiological. The
      various forms of spoilage and food poisoning caused by micro-organisms are
      preventable to a large degree by a number of preservation techniques, most of
      which act by preventing or slowing microbial growth. These include freezing,
      chilling, drying, curing, conserving, vacuum packing, modified atmosphere
      packing, acidifying, fermenting, and adding preservatives. In contrast, a smaller
      number of techniques act by inactivating micro-organisms, predominantly heating
      (pasteurization and sterilization). Complementary techniques restrict access of
      micro-organisms to food products, e.g. aseptic processing and packaging. New and
      'emerging' preservation techniques include more that act by inactivation. They
      include the application of ionizing radiation, high hydrostatic pressure, high
      voltage electric discharges, high intensity light, ultrasonication in combination
      with heat and slightly raised pressure ('manothermosonication'), and the addition
      to foods of bacteriolytic enzymes, bacteriocins, and other naturally-occurring
      antimicrobials. Major trends, reacting to consumers' needs, are towards the use
      of procedures that deliver food products that are less 'heavily' preserved,
      higher quality, more convenient, more 'natural', freer from additives,
      nutritionally healthier, and still with high assurance of microbiological safety.

PMID- 10885106
TI  - Microbiological safety of water.
AB  - Significant advances in water treatment over the last century have resulted in
      massive improvements in the microbiological safety of public drinking water
      supplies in the UK and the developed countries. Incidences of illness due to poor
      treatment or post-treatment contamination are rare, but when they occur tend to
      attract considerable media attention. A well managed water treatment works and
      supply system can provide high quality drinking water wherever in the world it is
      located. As a rule, throughout the world, private supplies tend to be of a poorer
      quality than public supplies, but poorly managed public supplies have the
      potential to make a large number of people ill and continued effort is needed to
      maintain and improve drinking water quality world-wide.

PMID- 10885108
TI  - Consumer perception and understanding of risk from food.
AB  - The study of risk perception has been punctuated with controversy, conflict and
      paradigm shifts. Despite more than three decades of research, understanding of
      risk assessment remains fragmented and incoherent. Until recently, food and
      eating has been viewed as a low-risk activity and perceived risk surrounded
      matters of hygiene or lack of food. Consequently, theories of risk have been
      constructed with reference to environmental and technological hazards, such as
      nuclear power, whilst neglecting food issues. However, following a decade of
      'food scares', attention has moved towards the study of food risk. Within this,
      food risk research has focused almost exclusively upon attempting to explain the
      divergence of opinion that exists between experts and the lay public whilst
      neglecting to address it. The following discussion provides a brief historical
      overview of theories and approaches that have been applied to the study of risk
      perception, continues with a summary of findings derived from food risk research
      and concludes with a discussion of methodological issues and some projections for
      future research.

PMID- 10885109
TI  - Risk communication: factors affecting impact.
AB  - The impact of risk communication depends upon a complex interaction between the
      characteristics of the audience, the source of the message, and its content.
      Audience perception of risk is influenced by demographic factors (e.g. age,
      gender), personality profile, past experience, and ideological orientation. It is
      also affected by cognitive biases (e.g. unrealistic optimism) and lay 'mental
      models' of the hazard. For food hazards, the important dimensions of risk are
      controllability, novelty and naturalness. The source must be trusted for a risk
      message to be effective. Trust is associated with believing the source is expert,
      unbiased, disinterested, and not sensationalising. To maximise impact, risk
      communications must have a content which triggers attention, achieves
      comprehension and can influence decision-making. It must be unambiguous,
      definitive and easily interpretable--rarely achievable particularly when risk is
      shrouded in scientific uncertainty. Risk messages initiate social processes of
      amplification and attenuation, consequently their ramifications are rarely
      controllable.

PMID- 10885110
TI  - Understanding life-style and food use: contributions from the social sciences.
AB  - The contribution of social sciences to the study of life-style and food use in
      Britain is illustrated by drawing on recent evidence of purchasing patterns,
      reports of the organisation of meals, snacks, eating out and images of the
      origins of food. Work discussed underlines a considerable degree of empirical
      complexity, demonstrates that the supply side as well as demand should be taken
      into account, and illustrates the manner in which even supposedly highly
      voluntaristic spheres of consumption activity may none the less be circumscribed.
      The article is prefaced by briefly contrasting the approach to 'life-style'
      adopted by market researchers, public health professionals and social theorists.
      It concludes with the proposal that in order to understand the complexity
      surrounding human food use, we may be advised to consider ensuring that the
      descriptive and conceptual tools being used can capture that complexity.

PMID- 10885111
TI  - Economic aspects of food-borne outbreaks and their control.
AB  - This paper begins with a discussion of the definition of an outbreak. It
      considers the portion of outbreaks in the general pattern of food-borne
      infectious disease. The methods used to identify outbreaks are described and the
      importance of the potential benefits and the economic impact of outbreak
      recognition and control and are discussed. The paper concludes by illustrating
      the economic impact of intervention using three infectious diseases botulism,
      Salmonella and Escherichia coli O157 as case studies of outbreaks.

PMID- 10885112
TI  - Control of vegetative micro-organisms in foods.
AB  - Microbes share our food whether we want them to or not. We need to control
      microbial proliferation in foods in order to avoid spoilage, to enhance flavour
      and, most importantly, to reduce the risk of food-borne illness. A broad spectrum
      of interventions are available to control microbial growth, but the most widely
      used is temperature. The use of temperature to control metabolically active
      bacteria is discussed briefly in the context of current practices. The marketing
      and legislative climate has provided an impetus to develop an ever-widening range
      of systems for microbiological control. This short review highlights some of the
      problems associated with such novel control systems, including selection of new
      spoilage agents or food-borne pathogens, and the difficulties of monitoring the
      efficiency of microbial control in the light of a better understanding of
      bacterial physiology.

PMID- 10885113
TI  - Control of bacterial spores.
AB  - Bacterial spores are much more resistant than their vegetative counterparts. The
      most dangerous spore-former is Clostridium botulinum which produces a potent
      neurotoxin that can prove fatal. The most common food poisoning from a spore
      former is caused by C. perfringens. Other food poisoning spore-formers include
      Bacillus cereus, B. subtilis and B. licheniformis. There are a number of non
      pathogenic spore-formers including butyric and thermophilic anaerobes that cause
      significant economic losses to food producers. Some unusual spoilage complaints
      have been reported, for example, B. sporothermodurans in UHT milk,
      Alicyclobacillus acidoterrestris in apple and orange juice and Desulfotomaculum
      nigrificans in hot vending machines. Control of spore-formers requires an
      understanding of both the resistance and outgrowth characteristics of the spores.

PMID- 10885114
TI  - Control of food-borne viruses.
AB  - There are two main food-borne virus infections. These are viral gastroenteritis
      caused by small round structured viruses (SRSV) of the Norwalk group and
      hepatitis A. Both infections are normally transmitted directly from person-to
      person, but on occasions they may also be food-borne or water-borne. Viruses do
      not multiply or produce toxins in foods, and foods merely act as vehicles for
      their passive transfer. Foods may be contaminated by infected food-handlers, and
      outbreaks frequently involve cold foods that require much handling during
      preparation. Foods may also be contaminated in their growing and harvesting areas
      by sewage polluted water, and molluscan shellfish have been particularly
      implicated. PCR and ELISA based methods are being developed for detection and
      typing of viruses in patients and also in food samples. Sensitive detection
      methods should facilitate the design of improved food processing methods to
      ensure virus-free food.

PMID- 10885115
TI  - Toxigenic fungi and mycotoxins.
AB  - Growth of commonly occurring filamentous fungi in foods may result in production
      of toxins known as mycotoxins, which can cause a variety of ill effects in
      humans, from allergic responses to immunosuppression and cancer. The most
      important mycotoxins are aflatoxins, ochratoxin A, fumonisins, trichothecenes and
      zearalenone. Aflatoxins are potent carcinogens and, in association with hepatitis
      B virus, are responsible for many thousands of human deaths per annum, mostly in
      non-industrialised tropical countries. Ochratoxin A is a probable carcinogen, and
      may cause urinary tract cancer and kidney damage in people from northern and
      eastern Europe. Fumonisins appear to be the cause of oesophageal cancer in
      southern Africa, parts of China and elsewhere. Trichothecenes are highly
      immunosuppressive and zearalenone causes oestrogenic effects in animals and man.
      Currently available records and statistics do not reflect the major role played
      by mycotoxins in mortality attributable to food-borne micro-organisms.

PMID- 10885116
TI  - Parasites.
AB  - Ill health related to food-borne infection transcends all geographical, political
      and cultural boundaries. The incidence of food-borne diseases continues to
      adversely affect the health and productivity of populations in most countries,
      especially non-industrialised ones. However, since the 1950s, the emphasis in the
      industrialised world had shifted away from addressing public health problems, to
      problems of chemical contaminants etc., but recently food-borne infections have
      again become of increasing concern to governments and the food industry.
      Improvements in international transportation means food can be distributed
      throughout the world, but so can the parasitic pathogens which contaminate foods.
      Alternatively, tourists are being affected abroad and possibly transmitting the
      pathogen to others at home. Thus, an increasing number of food-related illnesses
      are international in scope. In this review parasitic contamination of foods of
      animal origin, particularly meat and fish, will be discussed together with
      potential problems associated with water and unwashed fruits and vegetables.

PMID- 10885117
TI  - Food-borne protozoa.
AB  - Pathogenic protozoa are commonly transmitted to food in developing countries, but
      food-borne outbreaks of infection are relatively rare in developed countries. The
      main protozoa of concern in developed countries are Toxoplasma, Cryptosporidium
      and Giardia, and these can be a problem in immunocompromised people. Other
      protozoa such as Entamoeba histolytica, Cyclospora cayetanensis and Sarcocystis
      can be a food-borne problem in non-industrialised countries. C. cayetanensis has
      emerged as a food-borne pathogen in foods imported into North America from South
      America. Microsporidia may be food-borne, although evidence for this is not yet
      available. The measures needed to prevent food-borne protozoa causing disease
      require clear assessments of the risks of contamination and the effectiveness of
      processes to inactivate them. The globalisation of food production can allow new
      routes of transmission, and advances in diagnostic detection methods and
      surveillance systems have extended the range of protozoa that may be linked to
      food.

PMID- 10885118
TI  - Marine toxins.
AB  - Seafood products are important both nutritionally and economically. Within
      Europe, some 12 billion Pounds of fishery products are consumed annually and an
      enormous variety of species are available. Although seafood is rarely implicated
      in food poisoning, compared to other food sources, it does provide some specific
      human health hazards unique to this particular resource. Generally, these are
      toxins from toxic microscopic algae which accumulate through the food-chain. The
      toxins can cause various neurological and gastrointestinal illnesses and,
      potentially, consumers are exposed from seafood produced within Europe, from
      imported products, or from seafood eaten while travelling abroad. The symptoms of
      illness which may be encountered, the source and mode of action of the toxins,
      and some emerging problems are described. European legislation aims to ensure the
      quality and safety of seafood products by prohibiting sale of some toxic species,
      setting toxin limits, requiring monitoring and controlling imports.

PMID- 10885119
TI  - The future relationship between the media, the food industry and the consumer.
AB  - The relationship between the media, the food industry and the consumer is
      probably at its lowest point as we start the new millennium. The frequency of
      food scares appears to be increasing and news reports sometimes seem both
      sensational and polarised. High profile issues like the development of bovine
      spongiform encephalopathy in the UK and the dioxin contamination of poultry
      products in Belgium have undermined consumer confidence in the food industry. The
      recent genetically modified foods' debate has served to demonstrate the gulf that
      has grown between the food industry, food safety experts and the public. This is
      a rift that has been exploited by environmental pressure groups and fuelled by
      the media. This paper examines some of the underlying causes of the current air
      of mistrust that seems to exist between the media, the food industry and the
      consumer. Also, by examining the projected trends in these root causes, it draws
      some conclusions for the future relationship between the parties involved and
      suggests some changes that may improve the present situation.

PMID- 10885120
TI  - Paper bodies: a catalogue of anatomical fugitive sheets 1538-1687.

PMID- 10885121
TI  - Encounters with Winston Churchill.

PMID- 10885122
TI  - The "matchbox on a muffin": the design of hospitals in the early NHS.

PMID- 10885123
TI  - The origins and fate of James Currie's cold water treatment for fever.

PMID- 10885124
TI  - "An abortionist city": maternal mortality, abortion, and birth control in
      Sheffield, 1920-1940.

PMID- 10885125
TI  - Vesalius's method of articulating the skeleton and a drawing in the collection of
      the Wellcome Library.

PMID- 10885126
TI  - Alternative medicine in modern France.

PMID- 10885127
TI  - Dietetics, health reform and social order: vegetarianism as a moral physiology.
      The example of Maximilian Bircher-Benner (1867-1939).

PMID- 10885128
TI  - The historiography of nonconventional medicine in Germany: a concise overview.

PMID- 10885129
TI  - Shaping the medical market: on the construction of quackery and folk medicine in
      Dutch historiography.

PMID- 10885130
TI  - Women's medicine, women's culture: abortion and fortune-telling in early
      twentieth-century Germany and The Netherlands.

PMID- 10885131
TI  - The creation of the first overseas Pasteur Institute, or the beginning of Albert
      Calmette's Pastorian career.

PMID- 10885132
TI  - A Gallic affair: the case of the missing itch-mite in French medicine in the
      early nineteenth century.

PMID- 10885133
TI  - Cunning-folk in the medical market-place during the nineteenth century.

PMID- 10885134
TI  - Soothing syrups and teething powders: regulating proprietary drugs in Australia,
      1860-1910.

PMID- 10885135
TI  - The quest for Hickman.

PMID- 10885136
TI  - Edward Jenner's unpublished cowpox inquiry and the Royal Society: Everard Home's
      report to Sir Joseph Banks.

PMID- 10885137
TI  - Biomedical communication and the reaction to the Queensland childhood lead
      poisoning cases elsewhere in the world.

PMID- 10885138
TI  - Negotiating science and liberalism: medicine in nineteenth-century South
      Australia.

PMID- 10885139
TI  - Malaria in American troops in the South and Southwest Pacific in World War II.

PMID- 10885140
TI  - Paupers and the infirmary in mid-eighteenth-century Shrewsbury.

PMID- 10885141
TI  - Dietetics in medieval Islamic culture.

PMID- 10885142
TI  - The trade in medicinal leeches in the southern Indian Ocean in the nineteenth
      century.

PMID- 10885143
TI  - A tale of two sciences: bedside and bench in twentieth-century Britain.

PMID- 10885144
TI  - Hypoadrenia or "a bit of Addison's disease".

PMID- 10885145
TI  - The diary of Thomas Giordani Wright: apprentice doctor in Newcastle upon Tyne,
      1824-29.

PMID- 10885146
TI  - Medical practice and the law in the conflict between traditional belief and
      empirical evidence: post-mortem caesarean section in the nineteenth century.

PMID- 10885147
TI  - One hundred years of aspirin.

PMID- 10885148
TI  - Too little, too late? The home office and the asbestos industry regulations,
      1931: a reply.

PMID- 10885149
TI  - Endoscopic revision of failed external dacryocystorhinostomy.
AB  - Obstruction of the lacrimal pathways is a relatively frequent problem usually
      corrected by external dacryocystorhinostomy. Failure of the external approach may
      be due to an inadequate rhinostomy, excessive scar tissue production, anatomical
      anomalies or concomitant paranasal sinus infectious. The introduction of direct
      and angled endoscopes for paranasal sinus surgery and the refinement of
      endoscopic surgical procedures allows a complete intranasal exposure and surgical
      management of the lacrimal sac, even in cases of recurrent obstruction. The
      present work offers a retrospective review of the records of seven patients who
      underwent a revision endoscopic dacriocystorhinostomy (ENDCR) between January
      1994 and June 1997 for failed external dacryocystorhinostomy. The preoperative
      evaluation of the patients, the surgical technique and the postoperative
      management are examined in detail. A permanent dacryocystorhinostomy was obtained
      in six patients. One patient underwent a successful bilateral procedure. One
      patient experienced a persistent stenosis. There were no complications related to
      the surgical procedure. In our experience the revision endoscopic
      dacryocystorhinostomy offered several advantages, including a complete exposure
      of those anatomical anomalies or inflammatory changes of the normal structures
      that commonly hinder conventional external surgery. Although a larger series will
      further elucidate the efficacy of this procedure in failed external
      dacryocystorhinostomy, we recommend considering revision ENDCR as an alternative
      to the external revision technique.

PMID- 10885150
TI  - [Paranasal sinus mycoses].
AB  - In recent years there has been a marked increase in mycosis infections of the
      paranasal sinuses, attributed both to an increase in the survival of subjects at
      risk and improved diagnostic techniques (endoscopy, CT, MR) able to identify
      cases which had previously gone unrecognized and treated as aspecific chronic
      sinusitis. The present study involves 45 cases (4.3%) out of a total of 1050
      patients who had undergone endoscopic surgery for sinusopathy between April 1994
      and December 1998. Following the Katzenstein classification, the cases were
      broken down into non-invasive chronic mycoses or fungus ball (34 cases), allergic
      mycoses (7), chronic indolent invasive mycoses (3) and fulminating invasive
      mycosis (1 case). The mycetes most often involved was Aspergillus Fumigatus
      (76.9%). The recurrent symptom was facial algia, followed by nasal obstruction.
      Paranasal sinuses endoscopy did not modify the specific picture. CT presented
      such indicative signs as focal areas with non-homogeneous intensity, images of
      metal-like foreign bodies and endosinus calcifications in 84.4% of the cases. MR-
      performed in only 6 cases--always presented T2 images showing the typical signal
      void area corresponding to pathological lesions. All patients underwent
      endoscopic surgery of the paranasal sinus. The effectiveness of this treatment
      differed according to the clinical form. In the fungus balls surgery always
      resolved the pathology without requiring subsequent pharmacological treatment. In
      allergic mycosis, surgery improved the symptom of nasal respiratory obstruction
      but local drug treatment was required. With the aid of drug treatment, surgery
      resolved chronic indolent invasive mycoses and prevented the endocranial
      progression of complications. In the cases of fulminating invasive mycosis,
      timely surgery prevented the onset of endocranial complications and made it
      possible to perform antimycotic polychemotherapy to control the disease. This
      experience shows how important a protocol involving several different tests is in
      diagnosing the many clinical forms of paranasal sinus mycoses and distinguishing
      them from sinusopathies. Endoscopic surgery is indicated for all forms of
      paranasal sinus mycoses although the realistic objectives differ according to
      type.

PMID- 10885151
TI  - [Total laryngectomy: from hands of the general surgeon to the otolaryngologist].
AB  - In Europe early attempts at the total laryngectomy were performed in humans in
      the late 1800s by some Anglo-Saxon general surgeons. In Italy, Enrico Bottini,
      chief of General Surgery at the Hospital of Novara performed the first total
      laryngectomy in man in 1875, followed a few years later by Azio Caselli in Reggio
      Emilia and Francesco Durante in Rome. The latter perceived the need to modify the
      surgical technique currently being used at that time to remove the larynx. He
      agreed with the Berlin surgeons Gluck and Sorensen on the need to isolate the
      respiratory tract as completely as possible from the digestive tract in order to
      prevent ab ingestis complications and made his own personal modifications to the
      total laryngectomy techniques proposed by his German colleagues. Professor
      Francesco Durante proposed, and published in 1904, a new technique for total
      laryngectomy. In the years to come this technique was adopted by many other
      general surgeons. Among these, in 1912, his protege Gherardo Ferreri, who later
      became Director of Otology and Rhinolaryngology at Regia University in Rome, was
      the first otorhinolaryngologist to perform a total laryngectomy. And thus a new
      era in laryngology was born, evolving from a purely medical discipline to a topic
      of surgical interest.

PMID- 10885152
TI  - [Anatomo-functional study of 37 patients with monolateral chord paralysis].
AB  - The authors present a study of 37 patients affected by monolateral vocal cord
      paralysis in order to analyze etiology, degree of dysphonia and possible recovery
      of vocal function. The patients underwent the following tests: case history to
      determine the vocal characteristics prior to the lesion; video-laryngoscopy to
      define the position of the paralytic cord on the horizontal glottic plane and any
      compensation mechanisms; determination of the degree of dysphonia (light,
      moderate, severe, aphonia) on the basis of psycho-perceptive parameters;
      spectrography evaluated in classes (I, II, III and IV) according to Yanagihara.
      Analysis of the data obtained makes it possible to draw the following
      conclusions: the most frequent etiology encountered by the otorhinolaryngologist
      is surgical (particularly subsequent to thyroidectomy); the position taken by the
      paralytic vocal cord does not appear to determine the degree of dysphonia; during
      the period immediately after occurrence of the lesion (0-4 months) the vocal
      disorder is more intense and tends to be reduced thereafter, attenuated by a
      spontaneous compensation mechanism. In this regard, it must be pointed out,
      however, that such compensation can prove bad or even dangerous for good vocal
      function (falsetto voice); speech therapy makes it possible to nearly totally
      normalize vocal function in all patients presenting moderate dysphonia and in 60%
      of those with severe dysphonia. In the remaining 40% of those patients with
      severe dysphonia a partial improvement of vocal function was seen (from severe
      dysphonia to moderate dysphonia). This was determined by the fact that several
      negative prognostic factors came into play simultaneously in these patients (i.e.
      advanced age, longer time gap since the lesion occurred, position assumed by the
      paralytic cord) which prevented them from achieving better phonatory results.

PMID- 10885153
TI  - [Revascularized jejunum loop in hypopharyngeal reconstruction: oncological and
      functional results].
AB  - The aggressiveness of hypopharyngeal cancer makes broad resectioning of the
      circular pharyngolaryngoesophageal segments necessary, followed by reconstruction
      to restore the anatomical gap created as fully as possibly creating a
      neoesophagus with thin walls that can easily be released. Over the years several
      procedures have been fine tuned for reconstruction of the upper digestive tract
      employing transposed viscera, miocutaneous pedunculated flaps, revascularized
      fascio-cutaneous or visceral free flaps. Currently the revascularized jejunum
      loop is one of the most commonly used methods in the reconstruction of the
      hypopharynx. Its popularity is due to some anatomical and physiological
      advantages: it requires transposition of a brief intestinal tract anatomically
      well adapted to the reconstruction site, ensuring rapid functional recovery. The
      authors report the oncological and functional results obtained in 25 patients who
      underwent circular pharyngolaryngectomy followed by reconstruction with a
      revascularized jejunum loop. The percentage of transplant survival was 90% and
      local and general complications were reduced to a minimum. The functional results
      -both in terms of deglutition and phonation--were satisfactory while patient
      survival (6-37 months follow-up) was in line with that reported by other authors
      for the same tumor (47%). Although prognosis for hypopharyngeal-esophageal
      neoplasms is still quite poor, this experience shows that circular
      pharyngolaryngectomy followed by reconstruction with autotransplant of the
      jejunum is an excellent choice since it offers the patient a prompt, acceptable
      functional recovery and a fair quality for his remaining life.

PMID- 10885154
TI  - [Morphological study of the palatine tonsils: clinical and histopathological
      considerations].
AB  - This study examined 71 pediatric tonsillectomy patients through accurate case
      history and clinical examination, placing particular emphasis on pathologies
      concomitant to tonsillopathy. In an attempt to find anatomo-clinical
      correlations, these data were processed together with the results of a
      histomorphological study of thetonsil epithelium, performed on all tonsillectomy
      samples. The majority of these patients were females and none more than 13 years
      of age. Numerous pathologies were found associated with the tonsillopathy and in
      varying combinations, first and foremost of which was adenoid hypertrophy. Only
      approximately one fifth of the patients did not show any concomitant pathology of
      note. All patients presented a history of recurrent pharyngotonsillitis (at least
      4 episodes a year) with symptoms arising from 1 to 10 years prior to surgery. The
      concomitant pathologies included: respiratory, cutaneous and food allergies,
      asthma, obstructive sleep apnea, rheumatic diseases, etc. From the
      histomorphological point of view, particular modifications were found in the
      follicle epithelium and interstitial cells of the palatine tonsil. An exasperated
      fibrotic interstitial reaction and chronic duration of the disease appeared to
      prevent tonsil filter function, facilitating chronicization of the tonsillopathy
      or onset of recurrent infections and concomitant allergies. In the allergic
      patients the tonsil epithelium was thickened and compact and showed various
      degrees of chorion edema, in agreement with what is found in the literature. On
      the contrary, few morphostructural palatine tonsil mutations were found in those
      subjects which did not present any concomitant pathology or were affected by
      tonsillopathy of brief duration. All the histomorphological modifications
      encountered appear related to the individual patient history, confirming the
      hypothesis that tonsil epithelium can not only condition the evolution of
      tonsillopathy--reflecting the effect of various factors--but, above all, it
      directs the immune response, thus playing a role in the development of various
      concomitant pathologies.

PMID- 10885155
TI  - [Difficulties in the clinical, radiological and therapeutic evaluation of the
      initial stage of mucormycosis of the rhinosinus].
AB  - The initial diagnosis and subsequent treatment of rhino-orbital mucormycoses is
      quite difficult, particularly because the patient may find it difficult to accept
      aggressive therapeutic protocols, even when free of any endocranial involvement.
      The authors draw inspiration from a clinical case of rhino-orbital mucormycosis
      in a patient suffering from decompensated type I diabetes mellitus to discuss the
      main clinical-diagnostic and therapeutic aspects of this disorder. Timely medical
      surgical treatment proves extremely important for prognosis, preventing the
      intracranial extension of the lesion which is the cause of death in 80% of such
      cases. As regards the diagnostic protocol, careful clinical, radiological
      monitoring with CT and NMR--in strict interdisciplinary cooperation between
      otorhinolaryngologist, radiologist, ophthalmologist, microbiologist and
      histopathologist--is especially important. Radical surgery, at times demolition,
      associated with correction of the metabolic decompensation, systemic therapy with
      Amphotericin B and localbi-weekly medication for three months constitutes the
      best therapeutic protocol for treatment of this disorder.

PMID- 10885156
TI  - [Pleomorphic adenoma: a case treated by laryngotracheal resection and
      reconstruction].
AB  - Benign Pleomorphic Adenoma (PA) is a tumor rarely found in tracheal and
      laryngotracheal sites. A review of the literature published since 1922 has
      revealed only 30 certain cases of which 3 presented simultaneous involvement of
      both larynx and trachea. The present work describes the thirty-first case (the
      fourth with a laryngotracheal localization), diagnosed in a white, 40-year-old
      male who had been complaining of acute dyspnea for the last three years.
      Initially these symptoms had been interpreted as asthmatic crises. During one of
      these episodes, the patient underwent emergency tracheotomy and a
      laryngotracheoscopy revealed a rounded cricotracheal lesion with smooth surface
      and approximately 4 cm in cranio-caudal diameter. The mass occupied 90% of the
      air space and originated from the posterolateral right portion of the cricoid,
      and from the first 3 tracheal rings. CT and esophagoscopy ruled out its
      transmural invasion into the esophagus. Under rigid bronchoscopy, assisted NdYAG
      laser debulking was performed for biopsy purposes. The histological diagnosis was
      benign AP. For this reason a Grillo cricotracheal resection was performed with
      exeresis of the cricoid arch, mucosa of the cricoid plate and the first 4
      tracheal rings. Reconstruction of the respiratory tract was achieved through
      termino-terminal cricothyrotracheal anastomosis. The initial diagnosis was
      confirmed and the resection edges were without evidence of neoplasm. Post
      operative recovery proceeded without complications and the patient was discharged
      7 days after surgery. Endoscopic and radiological follow-up after 30 months is
      still negative for any neoplastic recurrences. The laryngo-tracheal lumen is
      within the norm and cord motility has been preserved. The authors then describe
      the clinical, anatomopathological and radiological elements which prove useful in
      evaluating tracheal neoplasms and they underline the problems of differential
      diagnosis between benign AP and adenoid-cystic carcinoma. In addition, the
      various therapeutic options are discussed with special attention being focused on
      surgery through external approaches. Given the location of the AP described, the
      Grillo procedure-most commonly used in cases of inflammatory cricotracheal
      stenoses-proved well suited to the loco-regional control of the neoplasm.
      Stringent respect for some parts of this surgical technique make it possible to
      reduce post-operative complications to a minimum.

PMID- 10885157
TI  - [Otzi, the man who came from ice (the most ancient repair of nasal bone
      fracture].

PMID- 10885158
TI  - Mental health in the 21st century.

PMID- 10885159
TI  - Mainstreaming mental health.

PMID- 10885160
TI  - Cross-national comparisons of the prevalences and correlates of mental disorders.
      WHO International Consortium in Psychiatric Epidemiology.
AB  - The International Consortium in Psychiatric Epidemiology (ICPE) was established
      in 1998 by WHO to carry out cross-national comparative studies of the prevalences
      and correlates of mental disorders. This article describes the findings of ICPE
      surveys in seven countries in North America (Canada and USA), Latin America
      (Brazil and Mexico), and Europe (Germany, Netherlands, and Turkey), using a
      version of the WHO Composite International Diagnostic Interview (CIDI) to
      generate diagnoses. The results are reported using DSM-III-R and DSM-IV criteria
      without diagnostic hierarchy rules for mental disorders and with hierarchy rules
      for substance-use disorders. Prevalence estimates varied widely--from > 40%
      lifetime prevalence of any mental disorder in Netherlands and the USA to levels
      of 12% in Turkey and 20% in Mexico. Comparisons of lifetime versus recent
      prevalence estimates show that mental disorders were often chronic, although
      chronicity was consistently higher for anxiety disorders than for mood or
      substance-use disorders. Retrospective reports suggest that mental disorders
      typically had early ages of onset, with estimated medians of 15 years for anxiety
      disorders, 26 years for mood disorders, and 21 years for substance-use disorders.
      All three classes of disorder were positively related to a number of
      socioeconomic measures of disadvantage (such as low income and education,
      unemployed, unmarried). Analysis of retrospective age-of-onset reports suggest
      that lifetime prevalences had increased in recent cohorts, but the increase was
      less for anxiety disorders than for mood or substance-use disorders. Delays in
      seeking professional treatment were widespread, especially among early-onset
      cases, and only a minority of people with prevailing disorders received any
      treatment. Mental disorders are among the most burdensome of all classes of
      disease because of their high prevalence and chronicity, early age of onset, and
      resulting serious impairment. There is a need for demonstration projects of early
      outreach and intervention programmes for people with early-onset mental
      disorders, as well as quality assurance programmes to look into the widespread
      problem of inadequate treatment.

PMID- 10885161
TI  - The burden of mental disorders: a comparison of methods between the Australian
      burden of disease studies and the Global Burden of Disease study.
AB  - The national and Victorian burden of disease studies in Australia set out to
      examine critically the methods used in the Global Burden of Disease study to
      estimate the burden of mental disorders. The main differences include the use of
      a different set of disability weights allowing estimates in greater detail by
      level of severity, adjustments for comorbidity between mental disorders, a
      greater number of mental disorders measured, and modelling of substance use
      disorders, anxiety disorders and bipolar disorder as chronic conditions. Uniform
      age-weighting in the Australian studies produces considerably lower estimates of
      the burden due to mental disorders in comparison with age-weighted disability
      adjusted life years. A lack of follow-up data on people with mental disorders who
      are identified in cross-sectional surveys poses the greatest challenge in
      determining the burden of mental disorders more accurately.

PMID- 10885162
TI  - Long-term prognosis of depression in primary care.
AB  - This article uses longitudinal data from a primary care sample to examine long
      term prognosis of depression. A sample of 225 patients initiating antidepressant
      treatment in primary care completed assessments of clinical outcome (Hamilton
      Depression Rating Scale and the mood module of the Structured Clinical Interview
      for DSM-IIIR) 1, 3, 6, 9, 12, 18 and 24 months after initiating treatment. The
      proportion of patients continuing to meet criteria for major depression fell
      rapidly to approximately 10% and remained at approximately that level throughout
      follow-up. The proportion meeting criteria for remission (Hamilton Depression
      score of 7 or less) rose gradually to approximately 45%. Long-term prognosis
      (i.e. probability of remission at 6 months and beyond) was strongly related to
      remission status at 3 months (odds ratio 3.65; 95% confidence interval, 2.81
      4.76) and only modestly related to various clinical characteristics assessed at
      baseline (e.g. prior history of recurrent depression, medical comorbidity,
      comorbid anxiety symptoms). The findings indicate that potentially modifiable
      risk factors influence the long-term prognosis of depression. This suggests that
      more systematic and effective depression treatment programmes might have an
      important effect on long-term course and reduce the overall burden of chronic and
      recurrent depression.

PMID- 10885163
TI  - Why does the burden of disease persist? Relating the burden of anxiety and
      depression to effectiveness of treatment.
AB  - Why does the burden of mental disorders persist in established market economies?
      There are four possibilities: the burden estimates are wrong; there are no
      effective treatments; people do not receive treatment; or people do not receive
      effective treatments. Data from the Australian National Survey of Mental Health
      and Wellbeing about the two commonest mental disorders, generalized anxiety
      disorder and depression, have been used in examining these issues. The burden of
      mental disorders in Australia is third in importance after heart disease and
      cancer, and anxiety and depressive disorders account for more than half of that
      burden. The efficacy of treatments for both disorders has been established.
      However, of those surveyed, 40% with current disorders did not seek treatment in
      the previous year and only 45% were offered a treatment that could have been
      beneficial. Treatment was not predictive of disorders that remitted during the
      year. The burden therefore persists for two reasons: too many people do not seek
      treatment and, when they do, efficacious treatments are not always used
      effectively.

PMID- 10885164
TI  - The genetics of mental illness: implications for practice.
AB  - Many of the comfortable and relatively simple models of the nature of mental
      disorders, their causes and their neural substrates now appear quite frayed. Gone
      is the idea that symptom clusters, course of illness, family history and
      treatment response would coalesce in a simple way to yield valid diagnoses. Also
      too simple was the concept, born of early pharmacological successes, that
      abnormal levels of one or more neurotransmitters would satisfactorily explain the
      pathogenesis of depression or schizophrenia. Gone is the notion that there is a
      single gene that causes any mental disorder or determines any behavioural
      variant. The concept of the causative gene has been replaced by that of genetic
      complexity, in which multiple genes act in concert with non-genetic factors to
      produce a risk of mental disorder. Discoveries in genetics and neuroscience can
      be expected to lead to better models that provide improved representation of the
      complexity of the brain and behaviour and the development of both. There are
      likely to be profound implications for clinical practice. The complex genetics of
      risk should reinvigorate research on the epidemiology and classification of
      mental disorders and explain the complex patterns of disease transmission within
      families. Knowledge of the timing of the expression of risk genes during brain
      development and of their function should not only contribute to an understanding
      of gene action and the pathophysiology of disease but should also help to direct
      the search for modifiable environmental risk factors that convert risk into
      illness. The function of risk genes can only become comprehensible in the context
      of advances at the molecular, cellular and systems levels in neuroscience and the
      behavioural sciences. Genetics should yield new therapies aimed not just at
      symptoms but also at pathogenic processes, thus permitting the targeting of
      specific therapies to individual patients.

PMID- 10885165
TI  - Psychiatric epidemiology: selected recent advances and future directions.
AB  - Reviewed in this article are selected recent advances and future challenges for
      psychiatric epidemiology. Major advances in descriptive psychiatric epidemiology
      in recent years include the development of reliable and valid fully structured
      diagnostic interviews, the implementation of parallel cross-national surveys of
      the prevalences and correlates of mental disorders, and the initiation of
      research in clinical epidemiology. Remaining challenges include the refinement of
      diagnostic categories and criteria, recognition and evaluation of systematic
      underreporting bias in surveys of mental disorders, creation and use of accurate
      assessment tools for studying disorders of children, adolescents, the elderly,
      and people in less developed countries, and setting up systems to carry out small
      area estimations for needs assessment and programme planning. Advances in
      analytical and experimental epidemiology have been more modest. A major challenge
      is for psychiatric epidemiologists to increase the relevance of their analytical
      research to their colleagues in preventative psychiatry as well as to social
      policy analysts. Another challenge is to develop interventions aimed at
      increasing the proportion of people with mental disorders who receive treatment.
      Despite encouraging advances, much work still needs to be conducted before
      psychiatric epidemiology can realize its potential to improve the mental health
      of populations.

PMID- 10885166
TI  - Mental health policy development in Africa.
AB  - Mental health issues are usually given very low priority in health service
      policies. Although this is changing, African countries are still confronted with
      so many problems caused by communicable diseases and malnutrition that they have
      not waken up to the impact of mental disorders. Every country must formulate a
      mental health policy based on its own social and cultural realities. Such
      policies must take into account the scope of mental health problems, provide
      proven and affordable interventions, safeguard patients' rights, and ensure
      equity.

PMID- 10885167
TI  - Mental health policy developments in Latin America.
AB  - New assessment guidelines for measuring the overall impact of mental health
      problems in Latin America have served as a catalyst for countries to review their
      mental health policies. Latin American countries have taken various steps to
      address long-standing problems such as structural difficulties, scarce financial
      and human resources, and social, political, and cultural obstacles in the
      implementation of mental health policies and legislation. These policy
      developments, however, have had uneven results. Policies must reflect the desire,
      determination, and commitment of policy-makers to take mental health seriously
      and look after people's mental health needs. This paper describes the development
      of mental health policies in Latin American countries, focusing on published data
      in peer-reviewed journals, and legislative change and its implementation. It
      presents a brief history of mental health policy developments, and analyzes the
      basis and practicalities of current practice.

PMID- 10885168
TI  - Towards a global alcohol policy: alcohol, public health and the role of WHO.
AB  - In 1983 the World Health Assembly declared alcohol-related problems to be among
      the world's major health concerns. Since then, alcohol consumption has risen in
      developing countries, where it takes a heavy toll. Alcohol-related problems are
      at epidemic levels in the successor states of the Soviet Union and are
      responsible for 3.5% of disability-adjusted life years (DALYs) lost globally.
      Substantial evidence exists of the relationship between the levels and patterns
      of alcohol consumption on the one hand and the incidence of alcohol-related
      problems on the other. Over the past 20 years, research has demonstrated the
      effectiveness of public policies involving, for example, taxation and
      restrictions on alcohol availability, in reducing alcohol-related problems. In
      the wake of rapid economic globalization, many of these policies at national and
      subnational levels have been eroded, often with the support of international
      financial and development organizations. Development agencies and international
      trade agreements have treated alcohol as a normal commodity, overlooking the
      adverse consequences of its consumption on productivity and health. WHO is in a
      strong position to take the lead in developing a global alcohol policy aimed at
      reducing alcohol-related problems, providing scientific and statistical support,
      capacity-building, disseminating effective strategies and collaborating with
      other international organizations. Such leadership can play a significant part in
      diminishing the health and social problems associated with alcohol use.

PMID- 10885169
TI  - Making mental health services work at the primary level.

PMID- 10885170
TI  - WHO and mental health--a view from developing countries.

PMID- 10885171
TI  - Mental health--getting beyond stigma and categories.

PMID- 10885172
TI  - Mental disorders and economic change--the example of Hungary.

PMID- 10885173
TI  - Removing the barriers to effective mental health care: a view from Turkey.

PMID- 10885174
TI  - WHO can help to combat mental health illiteracy.

PMID- 10885175
TI  - Using all opportunities for improving mental health--examples from South Africa.

PMID- 10885176
TI  - From evidence to practice: mental health in Australia.

PMID- 10885177
TI  - Getting down to cases--making mental health interventions effective.

PMID- 10885178
TI  - Expanding and strengthening the mental health care system.

PMID- 10885180
TI  - Lithium salts in the treatment of psychotic excitement. 1949.

PMID- 10885179
TI  - Lithium treatment for bipolar disorder.

PMID- 10885181
TI  - Global trade and health: key linkages and future challenges.
AB  - Globalization of trade, marketing and investment has important implications for
      public health, both negative and positive. This article considers the
      implications of the single package of World Trade Organization (WTO) agreements
      for public health research and policy, focusing on three themes: commodities,
      intellectual property rights, and health services. The main aims of the analysis
      are as follows: to identify how trade issues are associated with the
      transnationalization of health risks and possible benefits; to identify key areas
      of research; and to suggest policy-relevant advice and interventions on trade and
      health issues. The next wave of international trade law will need to take more
      account of global public health issues. However, to become more engaged in global
      trade debates, the public health community must gain an understanding of the
      health effects of global trade agreements. It must also ensure that its own facts
      are correct, so that public health is not blindly used for political ends, such
      as justifying unwarranted economic protectionism. "Healthy trade" policies, based
      on firm empirical evidence and designed to improve health status, are an
      important step towards reaching a more sustainable form of trade liberalization.

PMID- 10885182
TI  - Nutritional status of breastfed infants in rural Zambia: comparison of the
      National Center for Health Statistics growth reference versus the WHO 12-month
      breastfed pooled data set.
AB  - Cross-sectional data for breastfed infants in rural Zambia were used to evaluate
      the effect of applying two different data sets as a reference, i.e. the WHO 12
      month breastfed pooled data set and the National Center for Health Statistics
      (NCHS) growth reference in terms of prevalence of malnutrition (stunting,
      underweight, and wasting). A total of 518 infants who were attending mother-and
      child health clinics were included. Age, weight and length were recorded.
      Anthropometric Z-scores were calculated in two ways: by applying the NCHS growth
      reference and by using the WHO breastfed data set. Anthropometric Z-scores
      calculated using the breastfed data set were lower during the first 6-7 months of
      life compared with those calculated by applying the NCHS growth reference. This
      resulted in a higher proportion of children aged 0-6 months being classified as
      stunted and underweight using the breastfed data set versus the NCHS growth
      reference. After the age of 7 months, similar prevalences of stunting or
      underweight were observed. Relatively few infants were classified as wasted. In
      order to adequately assess the prevalence of stunting and underweight in
      breastfed infants, it is recommended that a new growth reference be developed, as
      has been initiated by WHO.

PMID- 10885183
TI  - Screening of Tanzanian women of childbearing age for urinary schistosomiasis:
      validity of urine reagent strip readings and self-reported symptoms.
AB  - The screening of women of childbearing age for haematuria, leukocyturia and
      proteinuria to detect urinary schistosomiasis can be confounded by several
      factors such as menstruation, pregnancy and genitourinary infections. We
      therefore undertook a study in an area endemic for Schistosoma haematobium in the
      United Republic of Tanzania to carry out the following: assess the sensitivity,
      specificity and predictive values--in women of childbearing age--of indirect
      indicators of urinary schistosomiasis, as measured by urine reagent strip
      readings; assess the predictive values of self-reported symptoms; and finally to
      estimate the morbidity attributable to S. haematobium. A total of 303 women (128
      and 175, respectively, living in high- and low-risk sites) participated in the
      study. Haematuria was more frequent among women excreting S. haematobium eggs
      than among those who did not (65% versus 32%). The predictive potential of all
      indirect disease markers was poor in the highly endemic site, while in the sites
      with low endemicity the negative predictive values were high. Among infected
      women, 54% of haematuria could be attributed to S. haematobium, but for patients
      with more than 10 eggs/10 ml the attributable fraction rose to 70%. Symptoms of
      "bloody urine" and "pain while urinating" were recalled significantly more often
      by women living in the highly endemic site. On a population level, one-third of
      the self-reported cases with bloody urine could be attributed to urinary
      schistosomiasis. Screening of women of childbearing age for urinary
      schistosomiasis using urine reagent strips can be biased in two directions. The
      prevalence of S. haematobium will be overestimated if other causes of haematuria,
      such as reproductive tract infections, are highly endemic. On the other hand,
      women with light or very light infections will be missed and will not be treated.
      This is of concern because genital schistosomiasis, a possible risk factor for
      the transmission of HIV, occurs among women even with light infections.

PMID- 10885184
TI  - Global public-private partnerships: Part I--A new development in health?
AB  - The proliferation of public-private partnerships is rapidly reconfiguring the
      international health landscape. This article (part I of two on the subject)
      traces the changing nature of partnership, and discusses the definitional and
      conceptual ambiguities surrounding the term. After defining global public-private
      partnerships (GPPPs) for health development, we analyse the factors which have
      led to the convergence of public and private actors and discuss the consequences
      of the trend toward partnership between UN agencies (including the World Bank)
      and commercial entities in the health sector. Generic factors such as
      globalization and disillusionment with the UN, and factors specific to the health
      sector, such as market failure in product development for orphan diseases, are
      examined. Reviewed are the interests, policies, practices and concerns of the UN,
      the private-for-profit sector, bilateral organizations, and governments of low
      income countries with respect to public-private partnership. While GPPPs bring
      much needed resources to problems of international health, we highlight concerns
      regarding this new organizational format. Part II, which will be published in the
      May issue of the Bulletin, presents a conceptual framework for analysing health
      GPPPs and explores the issues raised.

PMID- 10885185
TI  - The Urban Health Project, Karachi.

PMID- 10885186
TI  - Copper contamination from domestic tap water with a descaler.

PMID- 10885187
TI  - Gravidity and parity in postmenopausal American Indian women: the Strong Heart
      Study.
AB  - The fertility of a large sample of American Indian women participating in the
      Strong Heart Study was examined to determine which factors are associated with
      variation in completed fertility among women in this population. The Strong Heart
      Study (SHS) is a study of cardiovascular disease (CVD) and its risk factors in
      American Indians living in Arizona, Oklahoma, and the Dakotas. Data were derived
      from a baseline examination between 1989 and 1992 of approximately 1,500 men and
      women, aged 45-74, from each of the 3 SHS centers. A personal interview elicited
      demographic information, family health history, and information on several life
      style variables. A total of 1,955 ever-married, postmenopausal women were
      considered in these analyses. Women were considered to be postmenopausal if their
      menstrual cycles had stopped completely for at least 12 months, either because of
      natural or surgical processes. The average number of pregnancies (gravidity) for
      all women was 5.9, whereas the mean number of live births (parity) was 5.3. Women
      living in Arizona (5.6) and the Dakotas (5.8) had higher parity than those in
      Oklahoma (4.6). Furthermore, there was lower completed fertility in younger
      women: When American Indian women from all 3 centers were considered together,
      women born between 1910 and 1919 had a mean parity of 5.3, whereas women born
      between 1940 and 1949 had a mean parity of 4.0. Although previous research has
      suggested a relationship between parity and CVD risk factors, no linear
      associations between CVD risk factors and fertility were indicated in this
      population. We also examined the relationship of contraception, level of
      education, and income to fertility. While no significant relationship between
      contraception and the level of fertility was identified, there was a significant
      inverse linear relationship of both education and income with fertility. In
      summary, fertility rates in American Indian women are high, but appear to be
      decreasing in younger generations. Fertility is higher in those with less
      education and lower incomes.

PMID- 10885188
TI  - Tracking of familial resemblance for resting blood pressure over time in the
      Quebec Family Study.
AB  - The etiology of familial resemblance for systolic (SBP) and diastolic (DBP) blood
      pressure, both within a single time point as well as across time points, was
      assessed to determine how familial etiologies underlying a trait may change
      across time. SBP and DBP measurements were taken roughly 12 years apart in family
      members participating in the longitudinal Quebec Family Study. A longitudinal
      (bivariate) familial correlation model yields 3 types of correlations:
      intraindividual cross-time (e.g., father's BP at time 1 with his own BP at time
      2); interindividual within-time (e.g., father time 1 with child time 1); and
      interindividual cross-time (e.g., father time 1 with child time 2). In addition,
      the change in BP across time (i.e., time 1-time 2) is examined using a univariate
      family correlation model. This combined method is useful in assessing the degree
      to which the same familial factors are operating across time (interindividual
      cross-time correlations), as well as the degree to which different heritable
      components are involved across time (change score). Maximal heritabilities for
      SBP were about 70% at each time point, while for DBP the heritability was larger
      at time 1 (87%) than time 2 (39%). Both the change scores (48% for SBP and 54%
      for DBP) and the cross-time comparisons (58% to 72% for SBP and 63% to 65% for
      DBP) evidenced significant familial resemblance. These results illustrate how
      simple methodologies can be used to specify how familial etiologies underlying a
      trait may change across time. For BP, the model includes unique familial factors
      that are specific to each time measurement, and an additional familial factor
      which is common to both time points. The factors leading to differences in
      longitudinal familial resemblance for BP (i.e., the unique factors) may be
      primarily genetic in origin, while those leading to stability across time may
      include both genetic and familial environmental effects. Sex and/or age
      interactions with the genotypes are also suggested.

PMID- 10885189
TI  - A statistical analysis of the effect of warfare on the human secondary sex ratio.
AB  - Many factors have been hypothesized to affect the human secondary sex ratio (the
      annual percentage of males among all live births), among them race, parental
      ages, and birth order. Some authors have even proposed warfare as a factor
      influencing live birth sex ratios. The hypothesis that during and shortly after
      periods of war the human secondary sex ratio is higher has received little
      statistical treatment. In this paper we evaluate the war hypothesis using 3
      statistical methods: linear regression, randomization, and time-series analysis.
      Live birth data from 10 different countries were included. Although we cannot
      speak of a general phenomenon, statistical evidence for an association between
      warfare and live birth sex ratio was found for several countries. Regression and
      randomization test results were in agreement. Time-series analysis showed that
      most human sex-ratio time series can be described by a common model. The results
      obtained using intervention models differed somewhat from results obtained by
      regression methods.

PMID- 10885190
TI  - A look at the inheritance of height using regression toward the mean.
AB  - A reanalysis of the family growth study of Pearson and Lee (1903) leads to an
      explanation of the inheritance of height other than the one that has been offered
      until now. By acknowledging that the father may be incorrectly identified, this
      new analysis provides a more relevant explanation of the data: it fits parallel
      regression lines for sons and daughters, and is consonant with the theory that
      each parent contributes equally to the genetic makeup of their offspring, at
      least as far as height is concerned. The problem seems to lie in identifying the
      correct parents.

PMID- 10885191
TI  - How can we distinguish between mutational "hot spots" and "old sites" in human
      mtDNA samples?
AB  - New research into variation in mutation rates across nucleotide positions in
      human mitochondrial DNA (mtDNA) calls into question population genetics models
      that assume a constant mutation rate for all sites in a sequence, particularly
      for hypervariable control region segments I and II. Related to this research is
      discovering the extent to which highly polymorphic sites are really mutational
      "hot spots" rather than "old" sites rooted early in the phylogenetic tree. This
      issue is addressed through the analysis of linkage disequilibrium patterns in the
      mtDNAs of 10 human populations. Hot spots can be expected to show little or no
      disequilibrium since they can be interpreted as having randomly expressed
      patterns. In fact, the results suggest that many highly polymorphic sites are not
      old sites, but instead are hot spots. Suspected hot spots are listed and compared
      with hypervariable sites given by Wakeley (1993) and Hasegawa et al. (1993).

PMID- 10885192
TI  - Y-chromosome DNA haplotypes in north African populations.
AB  - The frequency distribution of Y-chromosome haplotypes at DNA polymorphism
      p49/TaqI was studied in a sample of 505 North Africans from Mauritania, Morocco,
      Algeria, Tunisia, Libya, and Egypt. A particularly high frequency (55.0%) of Y
      haplotype 5 (A2, C0, D0, F1, I1) was observed in these populations, with a
      relative predominance in those of Berber origin. Examination of the relative
      frequencies of other haplotypes in these populations, mainly haplotype 4 (the
      "African" haplotype), haplotype 15 (the "European" haplotype), and haplotypes 7
      and 8 (the "Near-East" haplotypes), permit useful comparisons with neighboring
      peoples living in sub-Saharan Africa, Europe, and the Near East.

PMID- 10885193
TI  - Variation in STR loci of the human myelin basic protein gene: north Portugal and
      Sao Tome e Principe.
AB  - Allele frequencies and a single-base substitution polymorphism for 3 short tandem
      repeat (STR) loci of the human myelin basic protein (MBP) gene were evaluated in
      North Portugal and Sao Tome e Principe. Strong linkage disequilibrium between
      loci MBPB and MBPC was found. However, the patterns of nonrandom allelic
      associations were very different in the 2 populations: levels of haplotypic
      diversity and heterozygosity were higher in the Sao Tome population. Similarly, a
      difference in the frequency of base substitution G-->A at position 124 was found:
      the frequency reached 4.1% in North Portugal and 0.5% in Sao Tome. In both
      populations it was always found to be associated with haplotypes B10/C11 and
      B12/C9.

PMID- 10885194
TI  - Improved haplotype analysis of human myelin basic protein short tandem repeat
      loci.
AB  - We report an improved haplotype analysis of the human myelin basic protein gene
      (MBP) short tandem repeat (STR) polymorphism. The polymorphic G-->A transition
      and 2 conventional STR polymorphisms, MBPA and MBPB, were simultaneously
      determined by an amplified product length polymorphism technique. After the MBPC
      fragments containing MBPA and MBPB were amplified, the linkage of these 2 STR
      loci was determined by a second amplification, using polymerase chain reaction
      (PCR) technique, of the isolated MBPC fragments. The present haplotype analysis
      dispensed with family studies for the haplotyping of MBPA and MBPB. Polymorphisms
      of the MBP loci studied in German and Japanese populations showed a high genomic
      variation. Haplotype analysis of the MBP loci showed distinct differences between
      the German and the Japanese populations. Consequently, haplotype analysis of the
      MBP loci promises to be useful in forensic identification and paternity testing.

PMID- 10885195
TI  - Molecular genetic diversity in 5 populations of Madhya Pradesh, India.
AB  - This paper presents data on the distribution of 3 amplified fragment length
      polymorphisms (D1S80, APOB, and YNZ22) in 5 populations of Central India. Using
      the polymerase chain reaction technique, 3 caste (Brahmin, Khatri, and Dhimer)
      and 2 tribal (Gond and Baiga) populations were studied for the 3 loci. The
      allelic variations observed in the caste populations are compatible with those of
      many Caucasian populations, but the caste populations showed significant overall
      and interpopulation variability within the region. D1S80 allele *24 varied from
      32% (Dhimers) to 42% (Brahmins). Allele *18 was not observed in Baiga tribal
      populations, but in caste populations it varied from 11% (Dhimers) to 24%
      (Brahmins). Both tribal populations showed higher frequencies of allele *31 (17%
      18%). For APOB, caste populations again showed bimodal distribution of alleles
      *35 and *37, but in tribal populations higher allele numbers (*47, *49) were also
      frequent. For YNZ22, extensive variation was observed for all populations
      studied. Allele *4 was the most common in caste populations, while alleles *2,
      *7, and *10 were prominent in tribal populations. The level of gene
      differentiation is not very high for the 3 systems studied in the 5 populations.
      Overall, allele frequency distribution, heterozygosity, and genetic diversity
      analysis show that the genetic diversity observed is socially and geographically
      structured.

PMID- 10885196
TI  - Sero- and molecular typing of Duffy blood group in Southeast Asians and
      Oceanians.
AB  - Duffy blood group was studied among malaria-endemic Thai and Indonesian
      populations: Hmong (n = 103), Akha (n = 218), Lisu (n = 44), Bugis (n = 95),
      Toraja (n = 77), Dani (n = 44), Mee (n = 80) and Irianese (n = 81). Phenotypes
      were studied by the ordinal indirect Coombs' test and genotypes were determined
      by the polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) test. DNA analysis was used to type the Duffy blood group system. Deduced
      allele frequencies of Fya (0.958-1.0) based on the phenotypes were similar to
      those in other populations in Southeast Asia and Oceania. The study revealed the
      presence of Fya-antigens showing weak reactivity to antisera as well as a
      discrepancy between the genotype shown by the PCR-RFLP study and that predicted
      by the phenotype. The PCR-RFLP study also suggested the presence of an
      alternative genetic basis for the Fy(a- b-) phenotype, which differs from the
      African type.

PMID- 10885197
TI  - Genetic structure of Native Andean populations from Argentina inhabiting
      different altitudes.
AB  - On the basis of erythrocyte and serum protein polymorphisms, we investigated the
      level of genetic differentiation among 3 Argentinian native populations sharing
      ethnic and morphological characteristics but inhabiting different altitudes in
      the Andes. Of the 15 loci studied, 8 are monomorphic. Phenotype distribution of
      the polymorphic systems are in agreement with Hardy-Weinberg equilibrium, except
      for malic enzyme (MOD), where a silent allele was found. The 2 highland
      populations exhibit a close genetic similarity, probably as a result of intense
      gene flow. The lowland population shows reduced genetic diversity, which suggests
      the influence of stochastic phenomena such as the founder effect.

PMID- 10885198
TI  - Polymorphism of the fourth component of complement in Turks.
AB  - An analysis of polymorphism in the fourth component of human complement (C4) was
      performed on EDTA-plasma from 142 unrelated, randomly selected Turks without
      collagen-vascular disease or recurrent infections. Plasma samples treated with
      neuraminidase and carboxypeptidase-B were subjected to high-voltage agarose gel
      electrophoresis followed by immunofixation. C4B allotypes were further detected
      in some samples by Western blots with monoclonal antibody 1228 (anti-C4B/Ch1
      reactivity). The frequencies of C4A and C4B alleles were determined. Allele
      C4B*5, which has been found to be relatively common in Asian (Oriental)
      populations, was not detected in this study. No specific predilection could be
      noted among the rare variants. C4A*3-C4B*1 was the most common haplotype (n =
      40/142, or 28%) but was found less frequently than in Caucasian populations. This
      finding may be the result of the limited number of samples examined. C4A and/or
      C4B null allotypes were seen in 49 of 142 (34.6%) subjects. The most frequent C4
      null allotype seen was C4B null (37/142, or 26%): 28 subjects had one C4B null
      allele; 1 had a homozygous deficiency of C4B (C4B*QO, *QO) and 7 had C4A*QO
      C4B*QO, a double heterozygous haplotype. Frequencies of homozygous haplotype
      C4A*Q0-C4B*Q0 in the population studied were found to be 0.007. The results of
      this study demonstrate that the genetic composition of the Turkish population
      exhibits both similarities and differences with the European population, and
      ranges between Caucasian and Mongoloid (Asian) populations.

PMID- 10885199
TI  - Sickle cell gene haplotypes in Relli and Thurpu Kapu populations of Andhra
      Pradesh.
AB  - We performed polymerase chain reaction analysis of 8 restriction-site
      polymorphisms in the beta-globin gene cluster to define haplotypes and provide
      hematological profiles of Relli and Thurpu Kapu caste populations in Andhra
      Pradesh, India. In all sickle cell homozygous subjects, the clinical
      manifestation of the disease is benign with elevated fetal hemoglobin levels
      (3.9%-21.1%). Clinical symptoms in some of the sickle cell homozygous subjects
      include jaundice, leg ulcers, and splenomegaly. Molecular analysis of the sickle
      cell gene (HBB*S) reveals the presence of the ubiquitous Arab-Indian haplotype in
      both populations. We encountered, for the first time, a rare, atypical haplotype
      ((+)-------) in a sickle cell homozygous individual of the Thurpu Kapu
      population, presumably the result of gene conversion.

PMID- 10885201
TI  - Impact of the integrated package of nutrition and health services.
AB  - Preschool children in 0-36 months of age are nutritionally the most vulnerable
      group. Nutrition and health services delivery through an ICDS programme aims at
      ameliorating the problems of malnutrition and infection. The extent of
      utilization of nutrition and health services in relation to nutritional status
      can provide valuable information on operational efficacy of the programme. In the
      present study, 610 preschool children (0-36 months) under an urban ICDS block
      were placed in three categories of service utilization viz. full, partial and
      none. The impact of the extent of service utilisation on nutritional status and
      morbidity was assessed over a one year period. The findings showed that complete
      utilization of all services resulted in significant improvement in nutritional
      status as assessed through anthropometric indices viz. height/age, weight/age and
      weight/height as percent NCHS median standard. Data on morbidity in children
      showed that the number of episodes and the duration of illness(es) were
      significantly lower when the services were utilized fully than when utilized
      partially or not utilized at all. Thus major efforts should go into the
      convergence of services and full utilization by the community.

PMID- 10885200
TI  - Sports related mild traumatic brain injury in adolescents.
AB  - While head injuries are not common in youth sports, they may have catastrophic
      results. Concussion is also referred to as mild traumatic brain injury (MTBI).
      Although the occurrence of head injuries has been studied more extensively in
      American football, the findings have wider application for any MTBI. Recently,
      more attention has been directed at other sports in which both boys and girls
      participate. The diagnosis of MTBI is based on subjective findings and subtle
      changes in mental status. Other cerebral injuries requiring emergent or urgent
      neurosurgical attention should be ruled out. Objective tests such as CT scans and
      Magnetic Resonance Imaging (MRI) are usually without significant findings in
      MTBI. Neuropsychological testing may demonstrate areas of deficiencies, however,
      results may be difficult to interpret because of confounding factors.
      Complications following MTBI have been known to occur. The most catastrophic of
      these is second impact syndrome. There are a variety of guidelines for return to
      play following a concussion, which have been designed in an effort to avoid
      problems such as second impact syndrome. These guidelines are based more on
      clinical experience than on scientific evidence. Education, good training and
      coaching techniques, improved equipment, and rule changes and enforcement, can
      all help in curbing the sports related head injuries in adolescents.

PMID- 10885202
TI  - Clinical risk factors for fatal diarrhea in hospitalized children.
AB  - It is important to determine the specific factors for diarrheal deaths in infants
      & young children to enable the intervention and reduce the mortality rates. This
      study aimed to identify these factors in children under five years of age,
      hospitalized with diarrheal complaints. Four hundred diarrheal children were
      included in the study. Twenty-seven (6.75%) of them died and 373 (93.25%)
      survived. The nutritional status of the patients was determined using weight for
      height for age as percentage of Harward Standard. It was found that severe
      malnutrition (p = 0.000 for weight for height ration < 70% and p = 0.036 for
      height for age < 85%), co-existent sepsis (p = 0.000), shigella infection (p =
      0.0014), hypoalbuminemia (p = 0.0000), hypoglycemia (p = 0.0002), hyponatremia (p
      = 0.016), hypokalemia (p = 0.0041) and metabolic acidosis (p = 0.0069 for pH <
      7.35 and p = 0.000 for HCO3 < 20 moL/l) were significant risk factors for
      diarrheal deaths in the univariate analysis. In the multivariate analysis, young
      age (under 6 months of age) ?Odds ratio (OR) 10.49, 95% confidence interval (CI)
      1.75, 62.75)?, moderate or severe dehydration (OR 8.17, 95% CI 1.53, 43.67),
      severe malnutrition (OR 0.04, 95% CI 0.00, 0.22 of weight for height < 70% and OR
      0.03, 95% CI 0.00, 0.36 for height for age < 85%), co-existent sepsis (OR 37.26,
      95% CI 6.94, 200.06), shigella infection (OR 23.01, 95% CI 3.08, 171.98),
      hypoalbuminemia (OR 0.11, 95% CI 0.02, 0.54), metabolic acidosis (OR 0.03, 95% CI
      0.00, 0.33 of HCO3 < 20 mMol/L) were significant risk factors. It is concluded
      that, in addition to electrolyte and fluid treatments, prevention of
      malnutrition, continuation of feeding which lessens weight loss and may prevent
      fatal hypoglycemia, and early detection and treatment of probable sepsis are
      important in reducing diarrheal deaths.

PMID- 10885203
TI  - Outcome of cases of persistent diarrhea after discharge.
AB  - After recovery from persistent diarrhea, some children have recurrent episodes of
      diarrhea and associated problems. We undertook this study to identify the risk
      factors responsible for this relapse. All patients reporting at 1 month follow up
      since discharge, with > 7 diarrheal days, or inadequate weight gain compared to
      the weight at discharge, constituted the failure group. All others constituted
      the non-failure group. Various risk factors were studied in 21 cases (failure
      group), and 42 controls (non-failure group). Univariate analysis revealed a
      significant association of hospital stay < 5 days (OR 10.6; 95% CI 3.13-36),
      working mothers (OR 8.5; 95% CI 2.5-27), poor socioeconomic status (OR 4.5; 95%
      CI 1.4-14) and presence of younger sibling (OR 3.69, 95% CI 1.1-12.6) with failed
      outcome. On logistic regression analysis, only hospital stay < 5 days (OR 11.7;
      95% CI 1.02-134.68) and female children (OR 17.65; 95% CI 1.26-246) remained
      significant. We therefore conclude, that a short hospital stay, limited optimal
      contact and limited health education adversely affects the outcome. Pediatricians
      should be more cautious while managing female children.

PMID- 10885204
TI  - Value of superficial cultures in diagnosing neonatal sepsis.
AB  - This study was conducted to determine the value of superficial cultures in the
      diagnosis of neonatal sepsis in our hospital. Sixty three babies, younger than 2
      weeks who were admitted with suspected sepsis were investigated. A total of 369
      cultures were obtained from these babies--252 (68.29%) superficial and 171
      (31.70%) deep cultures. External ear canal swab, umbilical cord swab and throat
      swab culture accounted for the superficial cultures. Blood culture, cerebrospinal
      fluid culture and i.v. catheter culture accounted for deep cultures. Of the 369
      cultures, 225 (60.97%) were positive for pathogens, which included Staphylococcus
      aureus, Klebsiella sp, Escherichia coli, Group B streptococcus and Enterococcus
      fecalis. The yield of pathogenic organisms was higher for superficial cultures
      (53.84%). All superficial cultures obtained during the study on each patient were
      simultaneously compared with the deep cultures by antimicrobial sensitivity
      method. The overall comparison showed that the practice of superficial cultures
      could be useful to predict the pathogenic organisms causing invasive disease.

PMID- 10885205
TI  - Cystic lymphangioma with special reference to rare sites.
AB  - A 10 year retrospective study of 45 cases of cystic lymphangioma (CL) in children
      is presented. There were 25 females and 20 males. Age ranged from 6 months to 8
      years. Common sites were involved in 38 and rare sites in 7 patients. Rare sites
      were--gluteal region (1), pelvis (1), retroperitoneum (1), mesentery (2),
      inguinal region (1) and inguinoscrotal region (1). The clinical presentation
      included sudden increase in size (25), lump abdomen (3), gluteal abscess (1),
      abdominal distension (1) and inguinal swelling (2). Diagnosis was established
      preoperatively in 38 cases, and after surgery and histopathology in 7 cases. Near
      total or subtotal excision was carried out in all cases. Facial nerve palsy (1)
      and recurrence (2) were the complications of surgery. The study is presented to
      highlight the occurrence of the cystic lymphangioma at rare sites to avoid
      diagnostic errors and unnecessary mutilating surgery.

PMID- 10885206
TI  - Spinal lipomatous malformations.
AB  - Spinal lipomatous malformations (SLM) include all the closed neural tube defects
      (NTD) with excessive lipomatous tissue in the spinal cord or filum terminale. We
      evaluated 65 cases of SLM seen & operated at our department in the last 7 years.
      Of these only 9 were asymptomatic and 8 were below 2 years of age. There were
      more males than females. In addition to subcutaneous lipoma many patients also
      had hypertrichiosis and dermal sinus as cutaneous makes. Twenty patients had foot
      deformity and 5 had unilateral limb shortening. Sixty-two patients had MRI and 3
      had CT myelogram for evaluation. These revealed 7 patients with Chiari
      malformations, 10 with focal syrinx and 2 patients underwent VP shunt for
      hydrocephalus. Sacral agenesis was seen in 5 patients. Clinical features were
      similar to other cases of spinal dysraphism except that sensory loss and trophic
      ulcer were more frequent. Intradural lipoma and tethering was seen in 18 cases
      whereas intramedullary lipoma & conus lipoma was seen in 40 & 7 cases
      respectively. Additional tethering lesion was seen in 1/3 cases and was treated
      simultaneously. Preoperative deficits improved in 28 cases and stabilized in 33
      cases. Three patients developed fresh deficits after surgery. We observed 8 CSF
      leaks and 4 wound infections in postoperative period. It is very clear from our
      data that a patient has about 95% chances that his neurological status may
      improve or stabilize following surgery and the risk of developing fresh deficits
      is about 5%. We, therefore, suggest that all patients of SLM should be treated
      with aggressive surgical management for best results.

PMID- 10885207
TI  - Critical appraisal checklist for qualitative research studies.
AB  - The ability to critically appraise literature is an essential skill for
      clinicians adopting a population perspective. Conventions exist for reporting and
      evaluating the quality of quantitative and epidemiological research. The same
      traditions do not exist in qualitative research for a number of reasons including
      the number of theories under which this type of research can be conducted and the
      subsequent incompatibility of indicators of quality. This paper presents a 10
      point checklist for assessing the quality of qualitative research in clinical
      epidemiological studies. We aim to provide a framework for critical appraisal as
      well as offer direction for qualitative researchers in designing and publishing
      their work.

PMID- 10885208
TI  - Fundamentals of clinical economics in health interventions.
AB  - Health economics is a science of efficient use of medical resources. Economic
      evaluation deals with both inputs or costs and outputs or consequences and is
      done when there are choices. The inputs or costs can be direct, indirect or
      intangible. The consequences can be measured as natural health units or utilities
      which aggregate multiple health units or quality adjusted life years. In the
      current health care scenario in India the cost data is usually lacking. An exact
      way for estimating the cost is elicitation of opportunity cost which is the value
      of time or input at its highest. The total cost is the cost of producing a
      particular quantity of the output and is made up of fixed and variable costs.
      Fixed costs do not vary with the quantity of output but variable costs do. In
      India, the total cost of health care provided by a multidisciplinary team can be
      estimated either by the 'per diem' approach which assumes no cost sharing by the
      departments, or by the allocation method which takes into account the quantity of
      service provided by each department and costs them individually. Cost
      effectiveness or utility and cost-benefit analysis are considered complete
      economic evaluation. Analyses are done from a pre-specified perspective which
      could be patients', payers', providers' or societal. Costs incurred at a later
      time are discounted. Such evaluations help us make informed decision to choose
      between various health interventions. Their increasing use in health research in
      the developing countries is needed.

PMID- 10885209
TI  - Focus group discussions in medical research.
AB  - Qualitative research methods have recently started to gain popularity in social
      and health sciences for determining a more holistic view of peoples' perceptions
      about health. Focus group discussions are frequently used to obtain perspectives
      and attitudes of people about issues, seek explanations for behavior, triangulate
      data obtained through other qualitative methods and generate hypotheses. To
      facilitate clinicians to comprehend the use of focus group methodology in the
      clinical field, the meaning, purpose, advantages, limitations and quality
      assurance measures of focus group discussions are described. The general
      requirements and the method for conducting focus groups are briefly explained. In
      addition, key issues that could be addressed by focus group methodology have also
      been highlighted.

PMID- 10885210
TI  - Randomized controlled trial and economic evaluation.
AB  - Conducting economic evaluation alongside clinical trials is an efficient way of
      getting valid and reliable information with minimum assumptions made during data
      collection. However, design of a randomised control trial (RCT) takes away
      several of the real world situations, the variations in resource utilisation,
      their cost due to close supervision and monitoring of the study subjects.
      Suitable sensitivity analysis has to be done to make the economic data obtained
      more pragmatic and hence utilised by the policy makers.

PMID- 10885211
TI  - Quantitative vs qualitative research methods.
AB  - Quantitative methods have been widely used because of the fact that things that
      can be measured or counted gain scientific credibility over the unmeasurable. But
      the extent of biological abnormality, severity, consequences and the impact of
      illness cannot be satisfactorily captured and answered by the quantitative
      research alone. In such situations qualitative methods take a holistic
      perspective preserving the complexities of human behavior by addressing the "why"
      and "how" questions. In this paper an attempt has been made to highlight the
      strengths and weaknesses of both the methods and also that a balanced mix of both
      qualitative as well as quantitative methods yield the most valid and reliable
      results.

PMID- 10885212
TI  - Newborn care at peripheral health care facilities.
AB  - Primary health centres, sub-district hospitals (first referral units) and
      district hospitals constitute the backbone of the health services in the country.
      These facilities are expected to cater to the care of the newborn infants who are
      delivered there, as well as those brought from the community with sickness. This
      paper, based on a survey in Orissa, and studies in a district hospital in
      Himachal Pradesh and a sub-district hospital in Haryana, is an attempt to piece
      together the present status of neonatal care at these facilities. In Orissa, the
      district and sub-district hospitals cater to a median of 100 and 30 deliveries
      per month, respectively. Most of the deliveries at these facilities are conducted
      by the nurses and not the physicians. Neonates are generally kept in the facility
      only for a day. Hardly any deliveries take place at primary health centres.
      Cesarean deliveries are mostly confined to the district hospitals. The commonest
      diagnosis of neonates admitted in the district and sub-district facilities is
      sepsis (septicemia pneumonia, skin infections, diarrhea and meningitis). Primary
      health centres seldom admit a sick neonate. It is reassuring to note that the
      outcome of sick neonates admitted at a functional district or sub-district
      hospital manned by a pediatrician is highly rewarding with low mortality rates.

PMID- 10885213
TI  - Preventing tuberculosis in childhood.
AB  - Almost half of the cases of tuberculosis requiring treatment may arise in
      children. The strategies to control tuberculosis in developing countries remain
      firmly focussed upon adults who are smear positive. The prevention of
      tuberculosis in childhood has two aspects: prevention of infection and management
      of infection once it has occurred. The steps for prevention of infection include
      early diagnosis of adults with tuberculosis who are culture positive but not yet
      smear positive. Use of ultraviolet lighting or at least large windows and
      ventilation in the area where patients are kept may reduce the infection rate. An
      appropriate regimen and supervised chemoprophylaxis to ensure good compliance may
      be an important step towards control of tuberculosis infection.

PMID- 10885214
TI  - Ciprofloxacin in children: is arthropathy a limitation?
AB  - Two hundred and nineteen children treated with Ciprofloxacin were observed for
      drug related adverse reactions (ADR). ADR was observed in 35/219 (15.98%)
      children, arthropathy in 2/219 (0.9%) children only. All the ADR were reversible
      even on continuation of therapy except one child with arthropathy and no
      permanent sequele or death occurred as a drug related ADR.

PMID- 10885215
TI  - Chromobacterium violaceum diarrhea.
AB  - This is the first case of Chromobacterium violaceum diarrhoea from coastal
      Karnataka reported in a 2 year 10 months old girl. Stool culture yielded
      Chromobacterium violaceum and was sensitive to ampicillin, gentamicin,
      chloramphenicol, erythromycin and septran. Patient completely recovered with
      ampicillin and gentamicin.

PMID- 10885216
TI  - Childhood trichobezoar.
AB  - Two cases of trichobezoar with unusual presentation in rural female children are
      described. The first one in a healthy asymptomatic child with no abnormal
      psychological behaviour and other one in an emotionally disturbed child with
      history of trichotillomania. Both were treated surgically with no recurrence. A
      physical sign of indentibility is discussed and literature is also reviewed.

PMID- 10885217
TI  - Unusual hand malformations with cardiac defects--a variant of heart--hand
      syndrome IV.
AB  - Reported below is the association of unusual hand malformations and congenital
      cardiac anomalies, possibly a variant of Heart--Hand syndrome IV in a 10 year old
      male. In addition to these malformations, he also had genitourinary defects. The
      differential diagnosis of polydactyly with cardiac defects is discussed along
      with a review of relevant literature.

PMID- 10885218
TI  - Serum cerebrospinal fluid magnesium levels in normal newborns.

PMID- 10885219
TI  - [It's human to make mistakes. Break the culture of fear and silence around
      medical errors!].

PMID- 10885220
TI  - [Measures for increased patient safety. How to apply experiences gained in
      industry?].

PMID- 10885221
TI  - [Preventive safety analyses. Methods from industry applied in health care].

PMID- 10885222
TI  - [What happens with child and adolescent psychiatric patients? Cooperation between
      pediatrics and psychiatry is required].
AB  - 1,420 child and adolescent psychiatric patients from a County Council in Northern
      Sweden were prospectively monitored during observation periods ranging from 5-20
      years. These follow-ups focused on the patients phi risk of future suicide, need
      of psychiatric care in adulthood, and risk of future criminality. In as much as
      every fourth child and adolescent psychiatric patient (male:female ratio = 1:2)
      required subsequent psychiatric care, while every third (male:female ratio = 2:1)
      demonstrated criminal behavior, these results indicate that improvements are
      needed in co-operative efforts linking child and adolescent psychiatry on the one
      hand with general psychiatry and social welfare authorities on the other.
      However, the majority of patients in general psychiatric care in corresponding
      age-groups were not the same former child and adolescent psychiatric patients. In
      a previous investigation of pediatric patients in ambulatory care it was found
      that every seventh patient was not physically ill although presenting with
      somatic symptoms, but suffered from undiscovered psychiatric problems.
      Considering the fact that patients in this group might well become patients in
      general psychiatry, yet never treated in child and adolescent psychiatry, then
      questions arise concerning ways to improve preventive measures and care. The
      following results also merit attention: 25 former child psychiatric patients died
      during follow-up. Mean age at death was 22 years (range 12-33 years). 14 suicided
      and another two died of "uncertain causes". None of those who suicided had
      previously been admitted to a child psychiatric unit after attempted suicide. The
      majority had suffered from serious psychosocial problems related to parental
      factors such as parental psychiatric illness, alcoholism/drug-abuse and neglect.

PMID- 10885223
TI  - [Hematopoietic growth factors in oncology and hematology. Recommendations for
      more cost-efficient use].

PMID- 10885224
TI  - [A case report. H2-antagonist efficient against drug-related weight gain].

PMID- 10885225
TI  - [Future transfusion specialists, supervisors of quality and safety].

PMID- 10885226
TI  - [A moment in medicine, part 9. Sensitive listening requires presence].

PMID- 10885227
TI  - [Schizophrenia--again! The reformed psychiatry suffers of a "knowledge virus"?].

PMID- 10885228
TI  - [General practitioners and treatment of depression--a personal task].

PMID- 10885229
TI  - [RSMH: no to a psychiatry which is only a branch on the tree of medicine].

PMID- 10885230
TI  - [Sigmund Freud, Sherlock Holmes and cocaine].

PMID- 10885231
TI  - [Dr Knock, a successful specialist in alternative medicine?].

PMID- 10885232
TI  - [Visual fields and driver's licence].

PMID- 10885233
TI  - [Antidepressive agents and cost-efficiency].

PMID- 10885234
TI  - [The effects of intravenous anesthetics, propofol, fentanyl and ketamine on the
      excitability of spinal motoneuron in human: an F-wave study].
AB  - We have investigated the effects of various intravenous anesthetics, propofol,
      fentanyl and ketamine on the excitability of spinal motoneuron using an F-wave
      analysis in a total of 28 patients. All patients were divided randomly into three
      groups as follows; 2 mg.kg-1 intravenous bolus injection followed by 6 mg.kg-1.h
      1 infusion of propofol (P group), 1 mg.kg-1 intravenous bolus injection followed
      by 1 mg.kg-1.h-1 infusion of ketamine (K group), and 5 micrograms.kg-1 injection
      of fentanyl (F group). The F-wave was determined after supramaximal
      electrostimulation of the median nerve in distal point. After establishing stable
      baseline values, intravenous injection of one of the three anesthetics was
      applied. The F-wave was recorded 3 minutes after the time of bolus
      administration. We found a significant (P = 0.018) reduction of the persistence
      from 77.5 +/- 15.2 to 40.9 +/- 16.8% in the propofol group. On the other hand, no
      significant changes in F-wave parameters were found in ketamine, or fentanyl
      group. These results suggested that motoneuron excitability in spinal cord could
      be inhibited by anesthetic dose of propofol, but not by ketamine or fentanyl.

PMID- 10885235
TI  - [Risk of bradycardia after endoscopic electrocautery of the upper thoracic
      sympathetic ganglia].
AB  - We evaluated risk of bradycardia after endoscopic electrocautery of the upper
      thoracic sympathetic ganglia (ETS). Enrolled in this study were 24 patients.
      Bradycardia, defined as heart rate below 50 beats per min continuing for more
      than 5 min, was found in 12 patients (50%). All patients were divided into two
      groups; bradycardia group and non-bradycardia group. Age, sex, region of
      electrocautery, fentanyl dosage, and operation time were not different between
      the two groups. Power spectral analysis of heart rate variability revealed that
      sympathetic activity decreased after ETS. Multivariate analysis indicates that
      postoperative-minimal heart rate depends upon preoperative heart rate at rest. We
      conclude that careful monitoring after ETS is necessary in a patient with heart
      rate below 60 bpm preoperatively.

PMID- 10885236
TI  - [Intra- and postoperative heart rate changes following propofol anesthesia; a
      comparison with isoflurane anesthesia].
AB  - Bradycardia during propofol anesthesia is well known, but bradycardia after
      propofol anesthesia has not been studied well. We compared perioperative heart
      rates in patients who had undergone gynecological surgery under lumbar epidural
      anesthesia supplemented with light general anesthesia using isoflurane and
      nitrous oxide in oxygen (Group Iso, n = 25) with those who had received lumbar
      epidural anesthesia supplemented with propofol (Group Prop, n = 25). The heart
      rates for the Group Prop were significantly lower (P < 0.05) than those for the
      Group Iso after the induction of anesthesia up to 2 hours after surgery. Two
      patients in the Group Prop developed bradycardia below 50 bpm 1 and 2 hours after
      surgery. In one of them intravenous atropine was necessary to treat bradycardia.
      We conclude that more attention should be paid to postoperative as well as
      intraoperative bradycardia in patients who receive propofol.

PMID- 10885237
TI  - [Total intravenous anesthesia with Diprivan (1% propofol emulsion) using a manual
      drip-infusion technique].
AB  - Continuous intravenous administration of Diprivan (1% propofol emulsion, P) is
      usually carried out using a syringe-pump or an infusion-pump to adjust the
      infusion rate. We assessed the accuracy of the infusion dose of P and the serum
      concentration of propofol by manual controls during anesthesia. Twenty eight
      patients, anesthetized with oxygen, P and vecuronium in combination with fentanyl
      and epidural block were randomly assigned to either of the following groups; P
      was administered using the drip-infusion (the group D, n = 14) or a syringe-pump
      (the group S; n = 14). In the group D, we used the drip-rate table to calculate
      the dose of P. We assessed (1) the total infusion volume of P which was
      calculated from the infusion rate and duration (Vc), and also measured by a
      calibrated cylinder (Vm) in the group D (n = 14) and group S (n = 14), and (2)
      the serum propofol concentrations 40 min after infusion of P (6 mg.kg-1.hr-1)
      were assayed using the HPLC. The Vc was well correlated with the Vm in the group
      D (r = 0.976) and in the group S (r = 0.974). Mean serum propofol concentrations
      of the group D and S were 2.50 +/- 0.57 and 2.35 +/- 0.62 micrograms.ml-1,
      respectively. The results suggest that the drip-infusion technique of P may be
      substituted safely by the syringe-pump for continuous total intravenous
      anesthesia.

PMID- 10885238
TI  - [Awake pronation of surgical patients with cervical spinal lesions].
AB  - Positioning of patients with cervical spinal lesions under general anesthesia may
      lead to serious neurological complications. The authors attempted awake pronation
      in eighteen patients to minimize the risks. In all patients, cervical instability
      or cervical spinal cord compression was diagnosed, and posterior fusion or
      laminoplasty under general anesthesia was planned. Naso-tracheal intubation was
      performed by broncho-fiberoptic scope under topical anesthesia and light
      sedation. After tracheal intubation, pronation was completed while patients were
      still awake. Twelve patients could change their position almost by themselves,
      and needed only a little assistance of the medical staff. After the patients
      settled in appropriate position, general anesthesia was induced. Neurological
      status was assessed before and after the intubation, and just before the
      induction of general anesthesia, to prove the absence of complications.
      Operations were accomplished without major troubles in all patients. During post
      anesthetic interviews, eight patients had memory of the positioning, but none of
      them had any complaints about the procedure. Awake pronation may be useful to
      minimize the risk of neurological complications related to positioning of
      surgical patients, and also need less assistance by medical staff.

PMID- 10885239
TI  - [Anesthetic management of heart transplantation].
AB  - We anesthetized a 47-yr-old man with end-stage hypertrophic cardiomyopathy for
      heart transplantation. This is the first case of heart transplantation from a
      patient with brain death, since the organ transplantation law had become valid in
      Japan. Anesthesia was induced and maintained with fentanyl and diazepam. Aseptic
      technique was used in inserting and securing all catheters. The patient was
      assisted by left ventricular assist system, and hemodynamic suppression at
      anesthetic induction was trivial. Since complete AV block was present at the
      termination of cardiopulmonary bypass (CPB), VVI pacing and infusion of
      isoproterenol were started. In addition, nitroglycerin was given for pulmonary
      vasodilation. The cardiovascular support used for weaning from CPB included
      dobutamine, isoprote-renol, dopamine and milrinone. Following weaning from CPB
      sinus rhythm appeared spontaneously and function of the transplanted heart was
      satisfactory. When the patient was transported to ICU reduction in doses of
      catecholamines was possible, and dopamine and milrinone were infused. The patient
      was extubated 10 hours after admission to ICU.

PMID- 10885240
TI  - [Continuous monitoring to detect brain ischemia during carotid endarterectomy and
      aortic arch replacement by near infrared spectrophotometory--a case report].
AB  - We report two cases in which continuous monitoring was used to detect brain
      ischemia by 8-channel electroencephalograph (EEG), transcranial Doppler (TCD) of
      middle cerebral blood flow velocities and near infrared spectrophotometric
      monitoring (NIR) of bifrontal area simultaneously. The symptom of brain ischemia
      was indicated by NIR and TCD but not by EEG following temporary cross-clamping of
      the common carotid artery during carotid endarterectomy. According to this sign
      we successfully used temporary shunt during CEA. On the other hand, these methods
      of monitoring did not show abnormal findings of cerebral blood flow disorders
      during aortic arch replacement. Nevertheless, neurologic disorders were
      complicated postoperatively. In conclusion, these methods monitor carotid artery
      blood flow but not vertebral artery blood flow.

PMID- 10885241
TI  - [Anesthetic management of the elderly patients with femoral neck fracture by
      sevoflurane and femoral nerve block].
AB  - Fracture of the femoral neck (FNF) is a significant cause of morbidity and
      mortality in the elderly, and the elderly with FNF are often high-risk patients
      for anesthesia. We studied 15 patients above 80 years of age with severe physical
      status (ASA III-IV). After femoral nerve block (for the pain of fracture) and
      lateral femoral cutaneous nerve block (for the cutting pain), surgical procedure
      was performed under general anesthesia by laryngeal mask airway under spontaneous
      ventilation. After the operation, morphine 2 mg was administered subcutaneously.
      In our experience, the majority of 15 patients cardiovascular status of remained
      stable, except one patient who needed ephedrine for hypotension and another
      patient who needed diclofenac sodium for post-operative pain relief.

PMID- 10885242
TI  - [Anesthetic management of thrombectomy for left ventricular huge mobile
      thrombus].
AB  - A 45 year-old male underwent thrombectomy for huge mobile thrombus and
      aneurysmectomy in the left ventricle. Despite of the patient's preoperative poor
      cardiac function and difficulties in weaning from cardiopulmonary bypass, he
      could recover with the aid of left ventricular bypass for 6 days without
      complications such as thromboembolism. Intraoperative transesophageal
      echocardiography was useful in observation of thrombus, decision making in the
      adaptation and type-selection of mechanical ventricular support, and evaluation
      of its efficacy.

PMID- 10885243
TI  - [Accidental pyriform sinus perforation with Savary-Gilliard esophageal bougie
      during general anesthesia].
AB  - A 71-year-old female with esophagohiatal hernia underwent a laparoscopic Nissen's
      fundoplication under general anesthesia. During the operation a Savary-Gilliard
      bougie was temporarily inserted to the esophagus to prevent esophagostenosis.
      After the emergence from anesthesia, the patient complained of severe back pain
      and developed tachypnea and a low SpO2 associated with an enlargement of
      mediastinal shadow on the chest X-ray, suggesting mediastinal perforation.
      Examination by endoscopy and thoracotomy revealed a pyriform sinus perforation
      reaching down to the mediastinum. This case demonstrates the possibility of
      accidental perforation by various devices inserted blindly to esophagus,
      especially during general anesthesia, and the importance of close observation of
      patients after the emergence from anesthesia.

PMID- 10885244
TI  - [A case of anesthetic management for re-expansion pulmonary edema of the
      dependent lung saved by superimposed HFJV during one lung ventilation for the
      thoracoscopic operation associated with bilateral pneumothorax].
AB  - A 21-year-old male with bilateral pneumothorax underwent thoracoscopic
      bullaectomy in the lateral decubitus position. General anesthesia was induced
      using thiopental 250 mg and suxamethonium 80 mg and maintained using the
      combination of the thoracic-epidural anesthesia with assisted spontaneous
      respiration. He was intubated with a tube equipped with mobile bronchial cuff. On
      the left bullaectomy, two lung ventilation (TLV) was applied and its course was
      uneventful. On the right, one lung ventilation (OLV) was done. Fifty minutes
      after the start of OLV of the left lung, percutaneous arterial hemoglobin
      saturation (SpO2) declined to 60% with PaO2 36 mmHg. Then, under super imposed
      HFJV (high frequency jet ventilation) added to manual assisted ventilation
      through the bronchial brocker, SpO2 increased rapidly to 100%. Postoperative
      chest X-p showed signs of re-expansion pulmonary edema (RPE) in the dependent,
      left lung. PaO2 after 25 minutes of hypoxic episode increased to 339.2 mmHg.
      About 2 hours later he was extubated uneventfully. We conclude that superimposed
      HFJV is very beneficial for treatment of the RPE of the dependent lung during OLV
      applied for thoracoscopic operation with bilateral pneumothorax.

PMID- 10885245
TI  - [Anesthetic management for an adult patient with secundum atrial septal defect
      associated with a large left-to-right shunt].
AB  - We describe the case of a 68-year-old woman with secundum atrial septal defect
      associated with a large left-to-right shunt and congestive heart failure. The
      patient with a pancreatic tumor was scheduled for hepatic cholangiojejunostomy
      and cholecystectomy. To determine the ratio of pulmonary to systemic flow (Qp/Qs)
      as an indicator for the magnitude of left-to-right shunt, oxymetric catheters
      were placed in the superior vena cava and pulmonary artery. In addition, oxygen
      delivery was assessed using superior vena cava oxygen saturation (SsvcO2).
      Although the patient was anesthetized with high-dose fentanyl to supplement
      nitrousoxide and sevoflurane, the Qp/Qs markedly increased after skin incision.
      Epidural local anesthetic was then administered. The Qp/Qs decreased to the
      preoperative value and the hemodynamic condition was improved thereafter. The
      operative course was uneventful. This case illustrates the potential usefulness
      of continuous measurement of the Qp/Qs and SsvcO2 for anesthetic management of
      adult patients with secundum atrial septal defect.

PMID- 10885246
TI  - [Anesthetic management of a patient with mitochondrial encephalomyopathy].
AB  - A 46-year-old female with mitochondrial encephalomyopathy underwent the
      replacement of right femur head under continuous epidural anesthesia. Considering
      that this disease is a neuromuscular disorder, general anesthesia should be
      avoided. In addition, the patients with mitochondrial encephalomyopathy tend to
      show increased concentrations of lactate and pyruvate caused by perioperative
      stress. Use of lactated Ringer's solution may elevate these concentrations. We
      managed this patient uneventfully with continuous epidural anesthesia and the use
      of acetated Ringer's solution during the perioperative period. We consider that
      continuous epidural anesthesia is useful for a patient with mitochondrial
      encephalomyopathy.

PMID- 10885247
TI  - [Accidental decrease in the air flow during air/oxygen sevoflurane anesthesia].
AB  - We describe our experience of an accidental decrease in the air flow during
      air/oxygen sevoflurane anesthesia. According to the malfunction of an air
      compressor system, dehydration of the compressed air was inadequate, and the wet
      air was delivered to the anesthesia machine. The moisture was formed at a flow
      control valve to cause a gradual decrease in the air flow. The low-pressure alarm
      did not work at that time, because the pressure of the air supply was normal.
      There are two types of medical air, one is produced from the ambient air by air
      compressor system and another is the synthetic air which is a mixture of oxygen
      and nitrogen. Although the synthetic air is always dry and clean, the former
      contains dust, bacteria, and moisture. There is a possibility that all of these
      particles cannot be excluded before use. Accordingly, we must check the air
      compressor system routinely when a source of the compressed air is used.

PMID- 10885248
TI  - [Anesthetic management for reconstruction of the superior vena cava by monitoring
      of peripheral venous pressure in a patient with a mediastinum tumor].
AB  - A 26-years-old man with a giant mediastinum tumor was scheduled for
      reconstruction of the superior vena cave and tumor resection. Anesthetic
      management for reconstruction of the superior vena cava was performed by
      monitoring of peripheral venous pressure. A bypass between the inominate vein and
      right auricula was made by using an artificial vessel before clamping the
      superior vena cava. When the superior vena cava was clamped, peripheral venous
      pressure increased suddenly to 42 mmHg. Immediately after the venesection from
      the peripheral vessel, it was possible to control peripheral venous pressure at
      about 20 mmHg. Blood was re-transfused from the femoral vein to the patient.
      Cerebral neurological symptom due to the increasing venous pressure was not
      detected. In conclusion, monitoring peripheral venous pressure during
      reconstruction of the superior vena cava in a patient with a mediastinum tumor
      may be a useful technique.

PMID- 10885249
TI  - [A case of acute pancreatitis that occurred after an operation of the lumbar
      spine].
AB  - A 56-year-old female, who had been suffering from heart failure and diabetes
      mellitus, underwent posterior instrumentation in the prone position and anterior
      interbody fusion in the right lateral decubitus position for pyogenic spondylitis
      between the fourth and fifth lumbar spine under general and epidural anesthesia.
      We induced hypotensive anesthesia by using continuous infusion of dopamine,
      prostaglandin E1 and nitroglycerin in order to prevent heart failure and reduce
      the blood loss. After the operation, the patient complained of upper abdominal
      pain, nausea and vomiting. We found high levels of serum amylase and other
      pancreatic enzymes. The massive gas of small intestine was pooled in abdominal X
      P, and the pancreatic head was slightly swollen in abdominal CT and US. Therefore
      we came to the diagnosis of postoperative acute pancreatitis. We administered a
      single bolus intravenous infusion of ulinastatine and continuous venous infusion
      of gabexate mesilate. As the serum amylase level gradually decreased, the patient
      improved. We suspect that postoperative pancreatitis was due to invasive
      anesthetic and surgical stress on the patient who had had pancreatitis in the
      preoperative period.

PMID- 10885250
TI  - [Myocardial ischemia during cesarean section in a patient with placental
      abruption].
AB  - A 27-year-old woman (38 week pregnant) was admitted to an obstetric hospital with
      an acute severe abdominal pain. At that time, the fetal heart sound was not
      audible. The diagnosis of placental abruption was made and she underwent an
      emergency cesarean section (C/S) under general anesthesia. She had anemia which
      became worse in the first few hours after C/S, requiring blood transfusion. ST
      depression was also present in the ECG during this period. Subsequently, we found
      an increase in myocin light chain, but not in troponin-T. On the 2nd
      postoperative day, pulmonary edema appeared and DIC was suspected. We treated her
      with nitrates, diuretics, protease inhibitors and oxygen by mask. She was
      discharged on 14th postoperative day with no other complications. Cardiac
      echogram showed no abnormalities, but a borderline change was seen in her
      exercise ECG. Depression of the ST segment has been reported in C/S patients, but
      this does not indicate myocardial ischemia (MI) nor treatment is necessary in
      most cases. In our case, the diagnosis was not conclusive, but in view of the
      risks associated with MI, patients with placental abruption should be managed
      strictly as if they have MI.

PMID- 10885251
TI  - [An anesthetic experience of epileptic focus resection in a nine month-old girl
      under monitoring by electrocorticography].
AB  - We report a successful electrocorticography (ECoG) monitoring for a epileptic
      cortical focus resection in a 9-month-old girl with uncontrollable epileptic
      seizures. Anesthesia was induced and maintained with nitrous oxide, oxygen, and
      sevoflurane with vecuronium. After the craniotomy, ECoG monitoring was used to
      locate the epileptic cortical lesion. During the procedure of subpial resection
      and gyrectomy, ECoG was repeatedly recorded. It was necessary to maintain
      adequate depth of anesthesia throughout the procedure to clarify the epileptic
      waves. For this purpose, sevoflurane (2.5%) with and oxygen (97.5%) under
      controlled-hyperventilation (PaCO2 30 mmHg), was useful for monitoring the
      epileptic seizure wave from cortical focuses properly.

PMID- 10885252
TI  - [An anesthetic experience of a patient with subacute myelo-optico-neuropathy for
      bilateral mastectomy].
AB  - A 79-year-old woman with subacute myelo-optico-neuropathy (SMON) underwent a
      bilateral mastectomy for breast cancer. She has been suffering from SMON for 32
      years. Her preoperative neurological examination revealed cryesthesia and
      dyskinesia in the lower extremity, and numbness in the crues. Physical
      examination revealed respiratory dysfunction. A combination of general anesthesia
      and epidural block was employed to minimize the dose of anesthetics which may
      affect the neuronal symptoms. Intraoperative course was uneventful and continuous
      epidural block was effective for postoperative pain control. There was no
      neurological deterioration postoperatively.

PMID- 10885253
TI  - [Multicenter study of cardiac events and anesthetic management of patients with
      ischemic heart diseases undergoing noncardiac surgery].
AB  - We designed a joint research project to investigate the incidence of ischemic
      heart diseases in patients undergoing noncardiac surgery and to define the risk
      of perioperative cardiac complications in these patients. Of the 8358 surgical
      patients in the 8 departments of anesthesiology between March 1997 and June 1997,
      328 (3.9%) had ischemic heart diseases. Among the 328 patients, 54 (16.4%)
      developed perioperative cardiac events, including myocardial infarction (3
      patients) and either lethal or potentially dangerous dysrhythmias (51 patients).
      Preoperative cardiac assessments were performed while the anesthetic techniques
      including intensive monitoring and perioperative prophylactic therapy were also
      employed. Patients with ischemic heart diseases received various types of
      preoperative evaluation to identify the degree of coronary artery disease and to
      assess the overall cardiac function. The patients were monitored using a
      multilead electrocardiogram, an arterial line, a central venous catheter, a
      pulmonary artery catheter, and by transesophageal echocardiography
      intraoperatively. Therapeutically, isosorbide, nitroglycerin, beta-blockers,
      calcium channel blockers, and/or nicorandil were administered to prevent
      perioperative ischemia. So far, no generally accepted management strategies have
      been established in patients with cardiovascular disorders based on large-scale
      outcome trials in Japan. Therefore, nationwide large multicenter trials are
      awaited with interest in order to establish helpful guidelines to improve the
      perioperative management and to reduce ischemia in cardiac patients undergoing
      noncardiac surgery.

PMID- 10885254
TI  - [Pain management for patients with cancer--current problems in a pain clinic].
AB  - One hundred and twenty-three patients with early or advanced cancer who had been
      referred to our pain clinic were studied retrospectively to investigate current
      problems with pain management for cancer patients. Pain due to advanced cancer
      and prolonged post-thoracotomy pain were two major reasons for referral. It was
      found that 51.7% of the patients with advanced cancer had not been treated
      appropriately with the WHO protocol for cancer pain relief before referral;
      however, increased administration of morphine did not necessarily relieve cancer
      pain, and in fact decreased the QOL of some patients; and 47.7% of patients with
      cancer pain were effectively treated with nerve block therapy. The present
      investigation also indicates that many patients who had undergone thoracotomy
      suffered prolonged post thoracotomy pain. Although post-thoracotomy pain was
      refractory to NSAIDs, trigger point injections with or without intercostal nerve
      block were effective in 65.4% of such patients. We conclude that further
      propagation of the WHO protocol for cancer pain relief, appropriate use of nerve
      block and establishment of practical guidelines for multidisciplinary management
      of pain are mandatory for improving the QOL of patients with cancer.

PMID- 10885255
TI  - [New studies on the history of anesthesiology (1)--A newly discovered truth on
      Woolley and Roe case after an interval of 50 years].
AB  - A famous medical accident that is widely known as Woolley and Roe case occurred
      on Oct 13th, 1947 at the Chesterfield Royal Hospital, England. The patients
      Albert Woolley and Cecil Roe underwent minor operations under spinal anesthesia
      using cinchocaine to develop spinal cord myelopathy with paralisis of bilateral
      legs. Both patients sued Dr James M. Graham, the anesthetist, and the Ministry of
      Health. Seven years later, Dr Graham and the Ministry of Health were given a
      verdict of not guilty, because three judges unanimously accepted the phenol
      theory proposed by a witness Prof Macintosh of Oxford University. He allged that
      phenol entered into the ampoule of cinchocaine through invisible cracks. Thus the
      plaintiffs were not compensated. Recentry Dr Hutter of Nottingham University
      found no validity of phenol theory and also no possibility of invisible cracks.
      Syringes and needles for spinal anesthesia were used to be sterilised by water
      boiling steriliser, and mineral acid was used for descaling the deposition of
      line at that time. Dr Hutter concluded that the severe spinal myelopathy occurred
      both in Woolley and Roe would have been caused by mineral acid which was conveyed
      into their subarachnoidal space by acid-contaminated syringes and needles.

PMID- 10885256
TI  - ["Medical micro biology for pharmacists" or pharmaceutical micro biology].

PMID- 10885257
TI  - [Treatment for hair loss].

PMID- 10885258
TI  - [Tinnitus. Diagnosis and therapeutic objectives].

PMID- 10885259
TI  - [Hepatitis C. Diagnosis, treatment and prevention].

PMID- 10885260
TI  - [Milk, milk products and cheese].

PMID- 10885261
TI  - The biology of violence.
AB  - As this decade of the brain unlocks the secrets of the mind, mental health
      professionals will gain a greater understanding of how biology shapes the
      biopsychosocial factors that generate some forms of violence.

PMID- 10885262
TI  - Clinician safety: assessing and managing the violent patient.
AB  - Many clinicians deny the possibility of violence occurring in their practices,
      and this denial has its roots in fear of violence or overconfidence in safety. To
      appropriately address the issue of violence, clinicians must engage in proactive
      behaviors and attitudes that will ensure their safety.

PMID- 10885263
TI  - Assessing the risk for violence.
AB  - In addition to taking steps to ensure their own safety, clinicians also have a
      role in predicting violence. In the past the clinician's ability to accurately
      assess the risk for violence has been seriously questioned. This chapter provides
      guidance for making acceptable predictions.

PMID- 10885264
TI  - Prevention of violence.
AB  - Rebuilding the village, increasing access to health, improving bonding and
      attachment dynamics, providing opportunities to increase self-esteem and social
      skills enhancing the adult protective shield, and minimizing the impact of trauma
      are presented as basic principles to change health behavior. The intent of
      putting these principles into practice is to strengthen the two key support
      systems of children, the family and the school, so that they can provide primary
      prevention of violence.

PMID- 10885265
TI  - Family violence.
AB  - Domestic and intimate partner abuse, child and adolescent physical and sexual
      abuse, and elder abuse constitute family violence. Such violence is responsible
      for a significant proportion of intentional injury and, accordingly, is a major
      public health problem. This chapter provides information on aspects of each type
      of family violence.

PMID- 10885266
TI  - Sexual violence: the victim.
AB  - Molestation and rape in childhood or adulthood is sexual violence. This chapter
      discusses issues for sexual violence victims and suggests several best practices
      for this population.

PMID- 10885267
TI  - Sexual violence: the perpetrator.
AB  - In addition to assessing and treating victims of sexual violence, mental health
      professionals are also called upon to provide similar services for sexually
      violent perpetrators. This chapter addresses these concerns along with the
      forensic issues surrounding those who commit sexual violence.

PMID- 10885268
TI  - Treating traumatized patients and victims of violence.
AB  - This chapter presents a thorough exposition of treating traumatized patients and
      victims of violence, addressing many aspects of trauma and victimization critical
      to a vast proportion of the work that mental health professionals find themselves
      doing.

PMID- 10885269
TI  - [Analysis method of eye movement control system].

PMID- 10885270
TI  - [Analysis of proteins during recovery from lens opacity--analysis of selenite
      cataract model using Sprague-Dawley and Wistar rat].
AB  - BACKGROUND AND PURPOSE: The cataract in Sprague-Dawley rats injected with
      selenite is a dense nuclear opacity that appears by 4 or 5 days after selenite
      injection and becomes irreversible by 7 days. Injection of Wistar rats with
      selenite resulted in a similar nuclear opacity by 4 or 5 days that began to
      recover transparency by 7 days. In this report, the cytoplasmic proteins were
      analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) in lenses from Sprague-Dawley and Wistar rats at 4 and 7 days after
      injection. RESULTS: In the opaque lens cells, degradation of the 31 kDa protein
      and cytoskeletal proteins (vimentin, spectrin, and actin) was observed during
      cataract development using SDS-PAGE and western blot analysis. During recovery
      from opacity, the decreased 31 kDa protein and the vimentin increased.
      CONCLUSION: The results suggest that the 31 kDa protein and the vimentin may be
      important for recovery of transparency in a reversible model of cataract
      formation.

PMID- 10885271
TI  - [Ascorbate free radical reductase activity in vertebrate lenses of some species].
AB  - PURPOSE: To clarify the function of ascorbate free radical (AFR) reductase in the
      lens antioxidation mechanism, we investigated the difference among species in AFR
      reductase activity in different vertebrate lenses. MATERIALS AND METHODS: Soluble
      and insoluble fractions were prepared from the lenses of frogs, guinea pigs,
      rats, rabbits, pigs, and calves. AFR reductase and diaphorase activity of each
      fraction was determined. RESULTS: AFR reductase activity in the lens soluble
      fraction was the highest in frogs. That of guinea pigs and rabbits was at the
      next level; there was only a little activity in rats and pigs, and none was
      detected in calves. Membrane-bound AFR reductase in the lens insoluble fraction
      was extracted by 0.3% Triton X-100. The membrane-bound enzyme activity was almost
      at the same level in frogs, rats, rabbits, and calves, and a little higher in
      guinea pigs and pigs. However, such species-specificity of AFR reductase activity
      as in the soluble fraction was not observed in 0.3% Triton X-100 extracts.
      Diaphorase activity was 3 to 9 times as much as AFR reductase activity in the
      soluble fractions of frogs, guinea pigs, and rabbits, but in 0.3% Triton X-100
      extracts of all vertebrate species used, it was very high, 108 to 311 times the
      AFR reductase activity. CONCLUSION: These results suggest that the lens soluble
      and membrane-bound AFR reductases are individual enzyme molecules and have
      different antioxidative functions. The lenses of frogs, guinea pigs, and rabbits
      contain a near-ultraviolet (UV) light absorbing compound, reduced pyridine
      nucleotide at a high concentration. Therefore, the soluble AFR reductase activity
      may be high in the vertebrate lenses with a near-UV light filter, and enhance the
      antiphotoxidation of ascorbic acid.

PMID- 10885272
TI  - [Correlation of indocyanine green angiography findings and expression of vascular
      endothelial growth factor in surgically excised age-related macular degeneration
      related choroidal neovascular membranes].
AB  - PURPOSE: We investigated the relationship between clinical classification by
      indocyanine green angiography (IA) and pathologic findings including the
      expression of vascular endothelial growth factor (VEGF) in age-related macular
      degeneration-related choroidal neovascular membranes. SUBJECT AND METHODS: The
      subjects were 15 patients with age-related macular degeneration who underwent
      surgical excision for choroidal neovascular membrane. The patients were
      classified into 4 types: Type I, hyperfluorescence in both early and late phases
      (n = 7); Type II, hyperfluorescence in the early phase only (n = 2); Type III,
      hyperfluorescence in the late phase only (n = 3); and Type IV, no
      hyperfluorescence in any phase (n = 3). The excised choroidal neovascular
      membranes were fixed and stained by hematoxylin-eosin and azan. They were also
      examined by immunohistochemical staining for VEGF. RESULTS: VEGF was expressed
      markedly in vascular endothelial cells and fibroblast-like cells of interstitial
      tissue of Types I, II and III. Its expression was weak in Type IV. CONCLUSION:
      Clinical classification by IA for age-related macular degeneration is consistent
      with the pathologic findings including the expression of VEGF.

PMID- 10885273
TI  - [Effects of leukotriene B4 receptor antagonist on experimental autoimmune
      uveoretinitis in rats].
AB  - PURPOSE: We evaluated the potential of leukotriene B4 receptor antagonist (LTB4
      RA) as an anti-inflammatory agent on experimental autoimmune uveoretinitis (EAU).
      MATERIALS AND METHODS: LTB4 RA was administered to Lewis rats twice a day on days
      0-10, 0-5, and 6-10 after immunization. Rats treated on days 0-10 after
      immunization were subdivided into three groups according to the dosage of LTB4
      RA. The eyes were examined histopathologically, and the expression of CD 45 RC in
      CD 4+T cells was analyzed. RESULTS: The inflammatory changes in the eyes of EAU
      were decreased in all groups treated with LTB4 RA in a dose-dependent manner. The
      treatment with LTB4 RA on days 0-10 after immunization achieved much higher
      uveitis suppression. The infiltration into eye tissues by neutrophils and
      lymphocytes was decreased by treatment with LTB4 RA. In treated groups, the CD 45
      RChigh subset decreased in the induction phase of EAU as compared with the
      untreated group. CONCLUSION: The suppressive mechanisms of LTB4 RA on EAU may be
      dependent on suppression of the activation of neutrophils and CD 4+T cells.

PMID- 10885274
TI  - [The difference in saccadic parameters among several visually guided tasks].
AB  - PURPOSE: The present study was undertaken to establish the effects of the five
      different paradigms (simultaneous, gap, overlap, delayed-memory and anti-saccade
      tasks) on saccade dynamics (duration, peak velocity, and amplitude). METHODS: We
      recorded ocular movements in 7 normal subjects, using infrared oculography with a
      visual stimulation system. RESULTS: The distribution of saccade accuracy in gap
      and overlap tasks had about the same steepness as that in simultaneous tasks, but
      that in delayed-memory and anti-saccade tasks was broader than that in
      simultaneous tasks. The distribution in anti-saccade tasks had a marked
      intersubject variability, and the average values of accuracy were hypermetric in
      four subjects. The peak velocity/amplitude ratio in simultaneous and gap tasks
      were higher than those of other tasks. The relationship between average of peak
      velocity of abduction and adduction was different, adduction was higher than
      abduction in simultaneous and gap tasks, and abduction was lower than adduction
      in delayed-memory and anti-saccade tasks. CONCLUSIONS: The dynamics in
      simultaneous tasks had about the same characteristics as in gap tasks, but were
      different from those in overlap, delayed-memory, and anti-saccade tasks. These
      results indicated that the marked differences in dynamic properties among
      different saccade types may reflect processes in the visuomotor system.

PMID- 10885275
TI  - [Lens epithelial cell damage and apoptosis in atopic cataract--histopathological
      and immunohistochemical studies].
AB  - PURPOSE: To elucidate the relationship between damage of lens epithelial cells
      and apoptotic cell death in patients with atopic cataract. METHODS:
      Histopathological and immunohistochemical studies were carried out using anterior
      lens capsules obtained at surgery from 13 patients with atopic cataract and from
      25 patients with senile cataract. RESULTS: No specific histopathological findings
      were found in the lens epithelial cells in atopic cases. However, the frequency
      and severity of histopathological findings such as flattening, nuclear pyknosis,
      and loss of cells were more frequent and more severe in atopic cases than in
      senile cases. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP
      biotin nick end labelling (TUNEL) method revealed that the mean ratio of cells
      containing fragmented DNA to whole epithelial cells was almost the same in both
      atopic and senile cases. However, the mean ratio of Bax-positive cells was
      significantly higher in atopic cases (mean +/- standard deviation, 29.1 +/-
      35.0%) than in senile cases (2.7 +/- 7.0%) (p < 0.05). The mean ratio of Bcl-2
      positive cells was significantly lower in atopic cases (1.4 +/- 3.4%) than in
      senile cases (44.3 +/- 35.7%) (p < 0.05). CONCLUSION: These results suggest that
      apoptotic cell death may play an important role in the development of lens
      epithelial cell damage in atopic cataract.

PMID- 10885276
TI  - [Visual evoked potentials and recognizing depths during changes in gaze
      direction].
AB  - PURPOSE: The neurophysiological mechanism underlying a phenomenon of depth
      perception that can not be explained by only the horizontal binocular retinal
      disparity was analyzed by means of visual evoked cortical potentials (VECPs).
      METHODS: A pair of pictures showing fourteen vertical lines with the same
      magnitude of horizontal retinal disparity were presented to eight normal subjects
      stereoscopically. Subjects were required to view the pair while changing the
      visual line direction. VECPs were measured while changing both the visual line
      directions and the sizes of the horizontal retinal disparity. RESULTS: The
      subjects perceived all lines as having the same magnitude of depth when they
      viewed the center position of the pictures stereoscopically (centro-version
      viewing). Shifting their visual line direction to the left end (laevo-version
      viewing), the depth magnitude of each line decreased gradually with increase of
      retinal eccentricity. Next, while maintaining the laevo-version the subjects were
      asked to make all lines of the same depth by changing the disparity magnitude of
      each line manually. Viewing this new version of the picture in the centro
      version, the further each line was separated from the line located in the center,
      the greater was the magnitude of its depth. However, no significant differences
      in amplitudes of VECPs, corresponding to those pictures were found. CONCLUSIONS:
      Our results suggest that differences of recognizable depth perception between the
      centro- and the laevo-version viewing occur in a higher order visual center than
      in the occipital and parietal zone when analyzing horizontal retinal disparity.

PMID- 10885277
TI  - [Quantitative evaluation of nystagmus by an image-analysis system].
AB  - PURPOSE: We attempted to apply a newly developed image-analysis system for
      measurement and analysis of nystagmus. METHOD: Eye movements were recorded by
      digital video through a head-mounted charge coupled device (CCD) camera. The
      recorded movie was converted into black and white in order to detect the area of
      the pupil. Horizontal and vertical eye positions were determined by calculating
      the centroid of the pupil. Torsional angle was calculated using the iris striate
      pattern around the pupillary margin. RESULTS: The parameters (amplitude, cycle,
      etc.) of nystagmus were calculated easily by the new image-analysis system from
      the recorded images. As examples, the foveation period was measured accurately in
      a case of jerky-type congenital nystagmus. Very regular cycles of intorsional
      attack period were revealed in a case of superior oblique myokymia. A case of
      cork-screw-like nystagmus showed a characteristic combination of large and small
      cycles unassociated with torsion. CONCLUSION: This image-analysis system was
      useful for quantitative analysis of nystagmus, and especially for measurement of
      torsion. Detailed waveforms and specific rhythms of nystagmus, which could not be
      recognized by observation, were demonstrated by this system.

PMID- 10885278
TI  - [Neovascular maculopathy associated with rubella retinopathy].
AB  - BACKGROUND: We report three eyes of two patients with rubella retinopathy which
      were associated with choroidal neovascularization in the macula. CASES: A 7-year
      old girl (case 1) and a 12-year-old girl (case 2) whose mothers had suffered
      rubella during their pregnancy revealed typical rubella retinopathy in both eyes
      and neovascular maculopathy in one eye at their initial visit to our clinic.
      Neovascular maculopathy developed in another eye of case 1 after a follow-up of
      10 months. RESULTS: The clinical characteristics indicated that 1. sudden visual
      loss occurs in children, 2. there is no external trigger such as eye injury, and
      3. the visual prognosis appears relatively good. CONCLUSION: Although neovascular
      maculopathy is rare in pediatric disease, the rubella retinopathy may have the
      potential to cause neovascular maculopathy.

PMID- 10885279
TI  - [Choroidal tuberculoma in a patient with acquired immunodeficiency syndrome].
AB  - BACKGROUND: In Japan, since the introduction of antituberculosis chemotherapy,
      the typical choroidal tuberculoma has been considered uncommon. A patient with
      acquired immunodeficiency syndrome (AIDS), because of the suppression of cell
      mediated immunity, faces the risk of tuberculous infection. CASE: A 30-year-old
      Malayan man had continuous cough for six months. He was diagnosed as having
      miliary tuberculosis of the lung and spine. Because the serum test of human
      immunodeficiency virus (HIV) was positive, he was also diagnosed as having AIDS.
      FINDINGS: Fundus examination showed a yellow white swollen lesion of the choroid
      with distinct border in his right eye, probably caused by tuberculosis. After
      three months of therapy with antituberculosis and anti HIV drugs, his systemic
      and ocular findings were markedly improved. CONCLUSION: Because of the recent
      increase in the incidence of tuberculosis with the epidemic of HIV prevailing in
      the world, the recognition of ocular tuberculosis is important.

PMID- 10885280
TI  - [Definition and classification of cardiomyopathies and specific
      cardiomyopathies].
AB  - The cardiomyopathies were previously defined as "heart muscle diseases of unknown
      cause" and were differentiated from specific heart muscle disease with known
      cause. With increasing understanding of etiology and pathogenesis, the difference
      between cardiomyopathy and specific heart muscle disease has become indistinct.
      Accordingly in 1995 WHO/ISFC task force, the definition and classification of
      cardiomyopathies were revised as cardiomyopathies are defined as disease of the
      myocardium associated with cardiac dysfunction. On the other hand, since the
      classification has become established clinical entities, the terminology is
      preserved as follows: dilated cardiomyopathy, hypertrophic cardiomyopathy,
      restrictive cardiomyopathy. While arrhythmogenic right ventricular cardiomyopathy
      is additionally included. The term specific cardiomyopathies is used to describe
      heart diseases that are associated with specific cardiac or systemic disorders.
      These were previously defined as specific heart muscle diseases. They included
      ischemic cardiomyopathy, valvular cardiomyopathy, hypertensive cardiomyopathy,
      inflammatory cardiomyopathy, metabolic cardiomyopathy, general system disease,
      muscular dystrophies, sensitivity and toxic reactions and peripartal
      cardiomyopathy. The cardiomyopathies are therefore classified by the dominant
      pathophysiology or, if possible, by etiological/pathogenetic factors.

PMID- 10885281
TI  - [Idiopathic cardiomyopathy--pathogenesis].
AB  - Etiology of hypertrophic cardiomyopathy and dilated cardiomyopathy has been
      thought to be different. In fact, most of the mutations of the genes of sarcomere
      were shown to be associated with hypertrophic cardiomyopathy. However, the same
      mutations of the genes such as mitochondria, dystrophin or actin have been
      reported in both the patients with hypertrophic and dilated cardiomyopathy.
      Recently, the importance of hepatitis C virus infection was noted in patients
      with cardiomyopathy, and the virus may also cause both hypertrophic and dilated
      cardiomyopathy. Therefore, the unknown factors may define the phenotype of
      cardiomyopathy. Increased expression of cytokines and nitric oxide has been shown
      and is being increasing recognized as important factors in the pathogenesis of
      cardiomyopathy.

PMID- 10885282
TI  - [Idiopathic cardiomyopathy: pathophysiology and hemodynamics].
AB  - Idiopathic cardiomyopathy is classified into three categories, namely,
      hypertrophic, dilated and restrictive cardiomyopathy. Pathophysiology and
      hemodynamics are quite different between the three types of cardiomyopathies.
      Hypertrophic cardiomyopathy is hemodynamically characterized by outflow
      obstruction and diastolic dysfunction. In dilated cardiomyopathy, progressive
      dilatation and systolic dysfunction of the left ventricle are predominant. This
      left ventricular remodeling is strongly associated with neurohormonal activation
      occurred in this disease. In restrictive cardiomyopathy, left ventricular
      distensibility is markedly impaired and differential diagnosis from constrictive
      pericarditis is often difficult.

PMID- 10885283
TI  - [Symptoms and electrocardiographic findings in cardiomyopathies].
AB  - Based on the national surveys in Japan, the most common symptoms of dilated
      cardiomyopathy(DCM) were dyspnea, palpitation, general fatigue and edema.
      Palpitation, dyspnea, general fatigue and anginal pain were common in
      hypertrophic obstructive cardiomyopathy(HOCM) and hypertrophic non-obstructive
      cardiomyopathy (HNOCM). Dyspnea was the most common symptom in constrictive
      cardiomyopathy (RCM). Electrocardiographic findings in DCM were not specific, and
      ST-T change, wide QRS complex, left ventricular hypertrophy and abnormal Q wave
      were frequently observed. In both of HOCM and HNOCM, frequent
      electrocardiographic abnormalities were ST-T abnormality, left ventricular
      hypertrophy and wide QRS complex. Moreover, abnormal Q wave was frequently
      observed in HOCM. Ventricular arrhythmia, including fatal ventricular tachycardia
      or ventricular fibrillation, was frequently found in patients with any type of
      cardiomyopathy.

PMID- 10885284
TI  - [Diagnostic algorithm of idiopathic cardiomyopathy].
AB  - In this review, diagnostic algorithm of idiopathic cardiomyopathy is discussed.
      In the primary care, most of the patients with cardiomyopathy are initially found
      by signs and symptoms of systolic/diastolic cardiac dysfunction and arrhythmia,
      and the myocardial involvement is recognized by chest roentgenogram and
      electrocardiogram. In the next step, echocardiography is extremely useful to
      confirm cardiac size, ventricular hypertrophy, systolic/diastolic function and
      structural abnormalities. After this examination, detailed diagnostic approaches
      including invasive strategy can be planned to each type of cardiomyopathy(DCM,
      HCM, RCM, ARVC). In each case, any etiology to develop myocardial disorder should
      be carefully examined to exclude secondary cardiomyopathy.

PMID- 10885285
TI  - [Echocardiography of idiopathic cardiomyopathies].
AB  - Echocardiography is useful to demonstrate cardiac abnormalities seen in
      idiopathic cardiomyopathies. Dilated cardiomyopathy is characterized by dilated
      cardiac chambers and diffusely hypokinetic wall motion. Hypertrophic
      cardiomyopathy is characterized by left ventricular hypertrophy with no known
      cause. Restrictive cardiomyopathy has diastolic failure with preserved systolic
      function. Echocardiography demonstrates the normal sized ventricles and the
      dilated atria. Recent advances in echocardiography include second harmonic
      imaging and tissue Doppler echocardiography. Second harmonic imaging can produce
      good quality images with high S/N ratio and is useful to delineate the
      endocardial border clearly and to show smoke-like echo in cardiac chambers.
      Tissue Doppler echocardiography can measure wall motion velocity. One of the
      potential application of this method would be to differentiate constrictive
      pericarditis from restrictive cardiomyopathy.

PMID- 10885286
TI  - [CT and MRI in the diagnosis of cardiomyopathy].
AB  - Two new noninvasive imaging modalities, electron beam computed tomography (EBCT)
      and magnetic resonance imaging(MRI), have emerged in recent years and have
      provided images of the heart with high temporal and spatial resolution. They
      provides accurate information of myocardial thickness, ventricular shape and
      volume, wall motion, and ventricular function in patients with cardiomyopathy. In
      addition, myocardial damage can be evaluated using contrast media. They can give
      unique diagnostic information above and beyond that of more traditional
      noninvasive modalities such as two-dimensional echocardiography, left
      ventriculography and radionuclide technique because both modalities acquire
      images in three dimensions. They have a possibility to become an alternative
      modality of the left ventriculography in the diagnosis of cardiomyopathy.

PMID- 10885287
TI  - [Nuclear medicine imaging for cardiomyopathy].
AB  - Nuclear medicine techniques have been applied to cardiomyopathy as well as in
      ischemic heart diseases. Various types of radiopharmaceutical including 201Tl and
      99mTc-labeled perfusion tracers, 123I-labeled fatty acid(BMIPP), sympathetic
      function (MIBG) and tracers for myocardial injuries have been used. Perfusion
      imaging identifies stress-induced ischemia associated with myocardial damage.
      Recent application of gated SPECT enables simultaneous assessment of ventricular
      function. 123I-BMIPP and MIBG can detect metabolic abnormality, which has
      diagnostic and prognostic value for hypertrophic cardiomyopathy. The MIBG uptake
      index, heart-to-mediastinum ratio, is known to show good prognostic value for
      estimating dilated cardiomyopathy. Nuclear medicine plays unique roles for
      evaluating functional and metabolic derangement in cardiomyopathy.

PMID- 10885288
TI  - [Endomyocardial biopsy: procedure and pathology].
AB  - Endomyocardial biopsy is one of the examinations seeking for the etiologies of
      myocardial diseases, different from the others evaluating physiological or
      functional states. The biopsy is most powerful for monitoring rejection of the
      transplanted hearts and anthracycline-induced cardiotoxicity. It can make a
      differential diagnosis between myocardial diseases based on the specific
      histological findings. Although the method is well established, the indication
      should be carefully selected, and attentions should be paid to prevent the
      possible complications. Besides histological approaches at light and electron
      microscopic levels, biochemical, pharmacological and immunological approaches on
      the biopsies will promise further understanding of the pathophysiological
      mechanisms underlying cardiac diseases.

PMID- 10885289
TI  - [Medical treatment for cardiomyopathies].
AB  - Newer drug therapy for patients with cardiomyopathies has been introduced with
      standard one. Beta-blocker therapy improves the prognosis in patients with
      ischemic and non-ischemic DCM and even in asymptomatic ones with LV dysfunction.
      The combined therapy of ACE inhibitor and angiotensin II receptor blocker, the
      intermittent intravenous infusion of inotropic agents and the supplement of
      phosphodiesterase inhibitor on induction of beta-blocker therapy also elucidate
      the effectiveness in DCM patients.

PMID- 10885290
TI  - [Cardiac pacing in cardiomyopathy].
AB  - Pacing is useful not only for therapies of arrhythmias but also for other cardiac
      disorders. In this article, the pacing therapies for idiopathic cardiomyopathies
      were reviewed. AV sequential pacing has been reported as beneficial methods to
      improve symptoms of hypertrophic obstructive cardiomyopathy(HOCM) patients, but
      the mechanisms and expectancy of efficacy of pacemaker implantation are not
      clarified. Prospective double blind studies to see the efficacy of pacing on HOCM
      patients were done and reported in the two continents, one was PIC study in
      Europe and the other was M-PATHY in the north America. Although they had the
      almost same protocol, the conclusions were opposite. However the results of the
      two studies showed the same tendency. The LVOTPG(left ventricular outflow
      pressure gradient) and QOL at the end of study after 6 months of DDD pacing were
      significantly improved in those two studies. But in double blind periods M-PATHY
      showed significant QOL improvement by AAI pacing as sham test, and so little
      significant in PIC study was. There were slight decrease of LVOTPG noticed by AAI
      pacing in the both studies. It seemed to be inappropriate to have chosen AAI
      pacing as a sham test, because implantation of leads in the heart might affect
      the right ventricular functions which would affect the left ventricular
      performance. It must be reconsidered to do prospective double blind test with
      employing real sham test like as implantation of generator without leads again.
      With all gained data so far, pacing therapy seemed effective and still one of
      alternative options for therapy of HOCM. On the other hands, effects of
      conventional DDD pacing on DCM is so limited but multisite pacing which is
      developing in recent, will be also one of options for therapy of CHF due to DCM.

PMID- 10885291
TI  - [Surgery for idiopathic cardiomyopathy].
AB  - Among the patients with idiopathic cardiomyopathy, those with dilated
      cardiomyopathy were surgically treated. Initial 18 patients were treated with
      partial left ventriculectomy(PLV) and thereafter PLV in 26 patients, septal
      exclusion technique (EVCPP) in 5 patients, or solo-valvular surgery in 12
      patients were applied according to the findings of the intraoperative cardiac
      echogram. The postoperative morbidity and mortality decreased after the selection
      of the operative procedures. Conclusively, left ventriculoplasty with PLV or
      EVCPP is a hope for the patients with dilated cardiomyopathy.

PMID- 10885292
TI  - [Heart transplantation in idiopathic cardiomyopathy].
AB  - Heart transplantation has just been resumed in Japan after 31 year's pause,
      whereas 2,400 cases per year have been carried in the United States. In the
      review article, several problems of this issue were discussed. For instance, the
      concept of brain death has not yet been accepted as a consensus in Japan.
      Therefore, we needed the legal support for the proceeding of heart
      transplantation. However, the recent success of heart transplantation will
      provide a new development of health care managements in the 21st century.

PMID- 10885293
TI  - [Cardiac gene therapy].

PMID- 10885294
TI  - [Prognosis of hypertrophic and dilated cardiomyopathy].
AB  - Hypertrophic and dilated cardiomyopathies are a heterogeneous disease, both
      clinically and genetically. Hypertrophic cardiomyopathy(HCM) is important causes
      of sudden cardiac death and death from congestive heart failure, although HCM has
      a relatively benign prognosis. The prognosis of dilated cardiomyopathy(DCM) has
      improved due to advances in earlier diagnosis and therapy, however, sudden
      cardiac death and death from congestive heart failure still occur in DCM.
      Accordingly, it is of importance to know possible risk factors on risk
      stratification for a high-risk group in HCM and DCM. Possible risk factors may
      contribute to the construction of therapeutic strategies for the prevention of
      sudden cardiac death or death from congestive heart failure in patients with HCM
      and DCM.

PMID- 10885295
TI  - [Apical hypertrophic cardiomyopathy].
AB  - Clinical and laboratory data of apical hypertrophic cardiomyopathy were reviewed
      based on our own experience of 120 consecutive patients, emphasizing various
      electrocardiographic characteristics including their natural course and the
      diagnostic capability of nuclear magnetic resonance imaging(MRI). This peculiar
      disease entity was mainly detected by annual health check and characterized by
      giant negative T waves(-1.2(-)-4.0 mV) in the middle-aged men. Transition from
      normal T wave to the inversion required several years and then usually unchanged,
      and may disappear within several years in occasional case, in which apical
      aneurysm was developed. The prognosis was generally good, but atrial fibrillation
      caused heart failure in 4 cases. MRI was conclusive to identify the diversity of
      muscular hypertrophy, and it was much more diagnostic than left ventriculography,
      because it was capable to obtain the exact short-axis view of many sections in
      addition to the long-axis view. Another look including echocardiography,
      ultrafast computed tomography, therapy and natural history was concisely
      reviewed.

PMID- 10885296
TI  - [Dilated form of hypertrophic cardiomyopathy].
AB  - To clarify pathological features of dilated form of hypertrophic cardiomyopathy
      (d-HCM), 14 autopsied hearts with d-HCM were studied. Prognosis of 23 cases with
      dHCM confirmed by myocardial biopsy specimens were evaluated. Pathological study
      revealed marked myocardial fibrosis(14/14), moderate to severe disarray(14/14),
      fibro-fatty degeneration of the outer layer of the left ventricle(13/14) and
      sclerosis of the intramural coronary arteries(mild, 5; moderate, 4). Degeneration
      of LV outer layer is an unique pathology in patients with d-HCM. Prognosis of 23
      patients with d-HCM is longer than usually supposed(Ten-year-survival rate from
      the initial symptoms: 78%).

PMID- 10885297
TI  - [From arrhythmogenic right ventricular dysplasia/cardiomyopathy(ARVD/ARVC) to a
      broader concept of ABCDE syndrome].
AB  - The concept on the presence of a peculiar disease, arrhythmogenic right
      ventricular cardiomyopathy, has been widely recognized to be involved in the
      category of cardiomyopathy. The authors believe this disease entity should be
      further expanded, and propose the new term "ABCDE Syndrome", abbreviated from
      Arrhythmogenicity, Brugada syndrome, Competitive sports, Death(especially sudden
      death) and Electric disturbance type of cardiomyopathy(ECM), be incorporated to
      encompass all facets of this category.

PMID- 10885298
TI  - [Mutations in genes for sarcomeric proteins].
AB  - Idiopathic cardiomyopathy(ICM) is by definition of unknown etiology. There are
      four clinical types of ICM; hypertrophic cardiomyopathy(HCM) characterized by
      ventricular hypertrophy associated with reduced compliance of the heart and
      accompanied by myofibrillar disarray, dilated cardiomyopathy(DCM) characterized
      by dilated ventricles associated with systolic dysfunction, restricted
      cardiomyopathy (RCM) and arrhythmogenic right ventricular cardiomyopathy(ARVC).
      Recent molecular genetic analyses have now revealed disease-associated mutations
      in ICM, especially in familial HCM and familial DCM. Mutations in 9 different
      disease genes (MYH7, TNNT2, TPM1, MYBPC3, MYL3, MYL2, TNNI3, CACT and TTN) cause
      HCM, while mutations in 3 different genes(CACT, DES and DMD) cause DCM in adults.
      In this review, I will summarize our current data on sarcomere mutations found in
      Japanese ICM, especially in HCM and DCM.

PMID- 10885299
TI  - [Mutations of the dystrophin gene in dilated cardiomyopathy].
AB  - X-linked dilated cardiomyopathy(XLDCM) is caused by mutations of the dystrophin
      gene, which was originally cloned as the responsible gene for Duchenne muscular
      dystrophy and Becker muscular dystrophy. Mutations due to XLDCM are centered on
      5' end of the gene, especially M-promoter and the adjacent region. However, other
      mutations are dispersed and cannot be characterized. Three mechanisms have been
      proposed by which the involvement of cardiac muscle is so severe in spite of the
      lack of skeletal muscle symptoms; 1) up-regulation of B- and P-dystrophin in
      merely skeletal muscle compensating for the defect of M-dystrophin, 2)
      dysfunction of some parts of dystrophin specifically essential to cardiac muscle,
      3) different expression patterns of mutant mRNA between cardiac and skeletal
      muscle.

PMID- 10885300
TI  - [Mitochondrial gene mutation].
AB  - Mitochondrial DNA(mtDNA) anomaly was emerging as a cause of idiopathic
      cardiomyopathy in addition to sarcomeric gene mutation. Meanwhile, several point
      mutations and deletions in mtDNA initially recognized as major causes of
      mitochondrial encephalomyopathies are now clarified to share 1% cause of diabetes
      mellitus. These results indicate that mtDNA mutations will be a significant
      candidate for cardiomyopathies. Screening of cardiomyopathic patients with mtDNA
      point mutations revealed that there were at least several % of mtDNA anomaly
      (MELAS type) among them. They also showed specific findings in ultrastructures of
      the cardiac muscle.

PMID- 10885301
TI  - [Genotype-phenotype correlations in familial hypertrophic cardiomyopathy].
AB  - Familial hypertrophic cardiomyopathy(FHC) is a complex cardiac disease with
      unique pathophysiological characteristics and a great diversity of morphological,
      functional, and clinical features. The results of molecular genetic studies have
      shown that FHC is a disease of the sarcomere involving eight different genes
      encoding proteins of the myofibrillar apparatus. Recent advances in genetic
      studies have provided insights into the heterogeneity of FHC clinical features.
      Analyses of genotype-phenotype correlations in FHC have shown that the age
      related penetrance, the pattern of the left ventricular hypertrophy, and the
      prognosis are different depending on the disease causing genes or the disease
      causing mutations. Understanding of the genotype-phenotype correlations in FHC is
      useful for management of the disease.

PMID- 10885302
TI  - [Epidemiology of dilated cardiomyopathy and hypertrophic cardiomyopathy].
AB  - Epidemiological study in Akita City revealed that the Japanese prevalence of
      dilated cardiomyopathy was 12.5 per 100,000 population at the end of 1994, and
      the mean age of patients with dilated cardiomyopathy was 63 +/- 12 years. The
      prevalence was comparable with that of 9.03 per 100,000 population in Niigata
      Prefecture and with that of 15 per 100,000 population by the echocardiographic
      mass screening in 2,673 subjects from 12 Japanese rural areas. The prevalence of
      hypertrophic cardiomyopathy in Japan was 170 to 574 per 100,000 population by
      mass screening. In future, the genetic analysis may compensate the limitation of
      morphological diagnosis of cardiomyopathies and also reveal new aspects of these
      disorders.

PMID- 10885303
TI  - [Myocarditis].
AB  - Myocarditis is an inflammatory disorder of the heart muscle, and is often under
      diagnosed in clinical practice. The etiology is most often viral in the developed
      countries, with a wide spectrum of natural history. While the association between
      acute myocarditis and dilated cardiomyopathy has been recognized for almost 200
      years, the strength of that association is unknown. Viral persistence and
      autoimmune mechanism have been extensively investigated using human sample and
      animal model. Some models have demonstrated post-myocarditic DCM in the chronic
      phase of viral or self-antigen inoculation. In addition, we also propose a new
      hypothesis with repetitive viral infection. These mechanisms will be summarized
      in this review.

PMID- 10885304
TI  - [Alcoholic heart disease].
AB  - Alcoholic heart disease is caused by a lifestyle in which alcoholics are continue
      to consume an excessive amount of alcohol over a long period of time. Total
      abstinence is a very effective way to treat them to prevent the development of
      the final stage of this disease. In contrast, repetitive drinking of massive
      amount of alcohol is very harmful and causes exacerbation of this disease. From
      our clinical studies, six candidates were nominated as symptoms of alcoholic
      heart disease, namely(1) tachyarrhythmias (incidence: 33%), (2) left ventricular
      hypokinesis(17%), (3) QT interval prolongation(17%), (4) hyperthickened LV
      wall(13%), (5) LV dilatation with pump failure: alcoholic cardiomyopathy(0.1%),
      and (6) sudden cardiac death (unknown %). In the beginning of alcoholic heart
      disease, the patient usually complains of no symptoms, and physical signs are
      quite poor. Ordinarily, either transient atrial fibrillation and/or left
      ventricular hypertrophy which is initially documented by electrocardiography or
      echocardiography is one of the first signals in the diagnosis. Without such early
      signals, an early diagnosis is impossible. To make a definite diagnosis of
      alcoholic heart disease, a clinical follow-up is by all means necessary.
      Improvement of cardiac function after total abstinence, it's worsening after
      drinking again, and again improvement after abstinence a second time is a
      diagnostic clue. In this follow-up study, electrocardiography and
      echocardiography were employed as important ways to gather date. In treatment,
      total abstinence is essential. To achieve this therapeutic goal, education of the
      patient is necessary, because approximately 70 per cent of patients with
      alcoholic heart disease fail to continue abstinence within two years even if they
      have good training.

PMID- 10885305
TI  - [Nutritional myocardial disorders].
AB  - It is well known that the nutritional deficiency possibly causes cardiac
      dysfunction. Although social hygiene has successfully diminished these cardiac
      dysfunction in developed countries, patients could be found in certain number
      under altered clinical profiles than before. Excess intake of carbohydrate drinks
      and carbohydrates should make beri-beri heart in youth. Not only deficiency but
      recent dietary habits of excessive nutrition in these developed countries are
      causing new types of nutritional cardiac dysfunctions such as obesity
      cardiomyopathy in morbid obese. On the other hand, anorexia nervosa which
      sometimes shows heart failure and sudden death combines with psychosomatic
      disorders. In this article, the pathogenesis and treatments are discussed
      focusing on these three cardiac disorders.

PMID- 10885306
TI  - [The myocardial diseases in endocrine disorders].

PMID- 10885307
TI  - [Peripartum cardiomyopathy].
AB  - Heart failure in the last month of pregnancy or with in 5 months after delivery
      has long been recognized as peripartum cardiomyopathy. Additional criteria
      include the absence of other identifiable causes of heart failure and the absence
      of other prior heart disease. Estimate of the incidence vary from 1 in 1300 to
      4000 pregnancies. The mortality rates of this disorder in the acute phases and
      subacute phases range from 25 to 50 percent the prognosis is especially poor in
      patients with cardiomegaly persisting > 6 months and in patients with low left
      ventricular ejection fraction.

PMID- 10885308
TI  - [Primary endocardial fibroelastosis].
AB  - Endocardial fibroelastosis is a disease characterized by a prominent
      proliferation of dense collagenous and elastic tissue in the endocardium with the
      occurrence of congestive heart failure and death in early life. There are,
      however, many recorded instances of infants surviving the initial illness and
      living up to or beyond puberty. The clinicopathological factors for good
      prognosis include the increase in myocardial mass of ventricle evaluated by
      ventriculography and the histopathologic evidence for compensatory myocardial
      cell hypertrophy in the biopsied myocardium.

PMID- 10885309
TI  - [Cardiac amyloidosis].
AB  - In our experience, QS pattern of poor R wave progression and atrio-ventricular
      block of varying degrees on electrocardiogram, cardiomegaly with pleural effusion
      on chest X-ray film, left ventricular wall thickening, pericardial effusion and
      findings suggesting left ventricular diastolic dysfunction on echocardiogram and
      increased right ventricular end-diastolic pressure in cardiac catheterization
      were frequently observed in patients with cardiac amyloidosis. Though none of
      these findings are specific, we should suspect cardiac amyloidosis as a
      possibility when some of these signs are observed in patients with chronic
      cardiac failure of unknown etiology. Left ventricular mass obtained from
      echocardiography could be useful predictive parameter of prognosis in patients
      with cardiac amyloidosis.

PMID- 10885310
TI  - [Myocardial sarcoidosis].
AB  - In this review article, clinical features characteristic of myocardial
      sarcoidosis including illness course, prognosis and treatment strategies are
      discussed. The pearl of settling the diagnosis of cardiac sarcoidosis is to
      consider cardiac involvement in all sarcoidosis patients, electrocardiographic
      and echocardiographic evidence is of greatest importance.

PMID- 10885311
TI  - [Myocardial involvement in rheumatic diseases].
AB  - The rheumatic diseases share many features. Clinically, they are often systemic
      diseases affecting multiple organs. Pathologically, these diseases share in
      common a diffuse vasculitis with an inflammatory process. Involvement of
      myocardium is also pathologically a common finding in rheumatic diseases,
      especially systemic sclerosis and dermatopolymyositis. Although clinical symptoms
      are often silent, potentially life-threatening manifestations are well known. Non
      invasive techniques such as nuclear imaging and echocardiography are useful to
      detect occult cardiac lesions. Clinically overt cardiac involvement portends an
      unfavorable prognosis. Early detection of subclinical involvement of myocardium
      is essential to improve prognosis.

PMID- 10885312
TI  - [Secondary cardiomyopathy accompanied by neuromuscular disorders].
AB  - There are many neuromuscular diseases associated with cardiomyopathy. Cardiac
      involvement with progressive muscular dystrophy (Duchenne and Becker type) and
      some type of limb-girdle muscular dystrophy were characterized by impaired left
      ventricular systolic function, such as dilated cardiomyopathy like status. In
      Friedreich ataxia various types of left ventricular hypertrophy were reported.
      While in myotonic dystrophy and Emery-Dreifuss muscular dystrophy, conduction
      disturbance and tachyarrhythmia are common types of cardiac manifestation. The
      severity of cardiac involvement in these diseases is not necessarily concordant
      with that of skeletal muscle. Recently the genes of these diseases were
      identified by linkage analysis. We review cardiac abnormalities of these
      diseases, especially relationship between severity of cardiac disorder and gene
      abnormalities.

PMID- 10885313
TI  - [Cardiomyopathy associated with mitochondrial disorders].
AB  - With understanding the biochemical and molecular characteristics of mitochondrial
      disorders, several point mutations or deficient of mitochondrial DNA have been
      identified in patients with mitochondrial dysfunction. The clinical
      manifestations of this disorders are heterogeneous and most patients show
      abnormality of the central nervous system, skeletal muscle, heart, kidney or
      these combinations. Especially, cardiac involvement is very important because it
      is determinant factor for the prognosis. There are two types of cardiac
      manifestation; cardiomyopathy and cardiac conduction defects. The former is
      usually hypertrophic, but dilated forms have been demonstrated. The latter is
      well known as one of three main symptoms in Kearn-Sayre syndrome. We discuss the
      pathogenesis, pathology and clinical manifestation of mitochondrial
      cardiomyopathy.

PMID- 10885314
TI  - [Myocardial disease in inherited disease].
AB  - To detect cardiac Fabry's disease, plasma alpha-galactosidase activity was
      measured in 230 male patients with left ventricular hypertrophy (LVH). Seven
      patients were diagnosed as having cardiac Fabry's disease. They did not have
      typical clinical manifestations of Fabry's disease. All seven had symmetric LVH.
      Endomyocardial biopsies revealed marked sarcoplasmic vacuolization in all five
      patients examined. Typical lysosomal inclusions with a concentric lamellar
      configuration were observed. Two novel mutations, A20P in exon 1 and M296I in
      exon 6, were detected in two patients, respectively. The remaining five had no
      mutations in the coding region for the alpha-galactosidase gene, and had marked
      decreases in the amount of alpha-galactosidase mRNA. Cardiac Fabry's disease
      should be considered as one of the cause of LVH.

PMID- 10885315
TI  - [Drug-induced myocardial disease--adriamycin cardiotoxicity].
AB  - Myocardial damage may be induced by several categories of drugs. Adriamycin is
      one of the most effective chemotherapeutic agents. Unfortunately, it develops a
      distinctive and life-threatening congestive heart failure by well-characterized,
      dose-dependent cardiac toxicity. Left ventricular ejection fraction determined
      using echocardiography or radionuclide angiography does not decrease sensitively
      and linearly with the adriamycin dose level. Cardiac function is preserved until
      a critical degree of myocardial damage is reached, after which myocardial
      performance deteriorates rapidly. Biochemical monitoring may be a novel sensitive
      and specific method for detecting subclinical myocardial damage. Abnormal cardiac
      adrenergic neuron activity evaluated with radiolabeled MIBG, impaired myocardial
      glucose utilization measured with F-18-FDG and plasma brain natriuretic peptide
      levels increased due to cardiac dysfunction may be particularly sensitive markers
      of adriamycin cardiotoxicity. It is hoped that prospective clinical study reveals
      the values of these biochemical markers.

PMID- 10885316
TI  - [HLA and hepatitis C virus positive cardiomyopathy].
AB  - The relationship between HCV (hepatitis C virus) and the susceptibility of
      cardiomyopathy has been indicated, but the detailed mechanism for close
      association is still unknown. It is well known that the human leukocyte antigen
      (HLA) may regulate the development of chronic hepatitis in HCV positive patients.
      We have analyzed the distribution of HLA class II alleles in Japanese patients
      with HCV antibody positive dilated cardiomyopathy (DCM) and hypertrophic
      cardiomyopathy (HCM), and HLA-DPB1*0901 was significantly increased in HCV Ab
      positive DCM, and the HLA-DRB1*0901-DQB1*0303 haplotype was in HCV Ab positive
      HCM. These results suggested that molecular mechanism for the development of
      cardiomyopathy mediated by HCV is different between DCM and HCM.

PMID- 10885317
TI  - [Differential diagnosis of idiopathic cardiomyopathy from ischemic cardiomyopathy
      and hypertensive heart disease using non-invasive methods].
AB  - Although, the diagnosis of idiopathic cardiomyopathy is determined by cardiac
      catheterization including myocardial biopsy, non-invasive diagnosis is important.
      The most useful method is nuclear cardiology to differentiate dilated
      cardiomyopathy from ischemic cardiomyopathy. Cardiac images in ischemic
      cardiomyopathy have wider perfusion and metabolic defects than in dilated
      cardiomyopathy using Tl-201, Tc-99m perfusion tracers, I-123 BMIPP, N-13 NH3 and
      F-18 FDG. The degree of heterogenecity of the myocardium is higher in ischemic
      cardiomyopathy than in dilated cardiomyopathy by these tracers. Left ventricular
      hypertrophy is common finding in hypertension and hypertrophic cardiomyopathy.
      However, in hypertensive heart disease the left ventricular wall thickness rarely
      exceed than 20 mm, and the septal wall thickness/posterior wall thickness is not
      more than 1.5, which are frequently shown in hypertrophic cardiomyopathy. Right
      ventricular hypertrophy near the ventricular septum is also one of the
      characteristic findings in hypertrophic cardiomyopathy.

PMID- 10885318
TI  - [Molecular aspects of cardiac hypertrophy and their implications in
      cardiomyopathies].
AB  - Cardiac hypertrophy or hypertrophy of cardiomyocytes is an adaptive response of
      the heart against an intrinsic or extrinsic damage in cardiomyocytes. A typical
      intrinsic defect causing cardiac hypertrophy is the sarcomere mutations found in
      hypertrophic cardiomyopathy (HCM) and extrinsic defects include cardiac ischemia,
      pressure- or volume-overload, metabolic diseases and arrhythmias. The
      hypertrophic response is a compensatory mechanism to augments cardiac output,
      however, sustained hypertrophy may lead to systolic dysfunction or de
      compensation state. It is well known that some patients with HCM develop to
      dilated-phase or burn-out phase, which resembles dilated cardiomyopathy (DCM). In
      this review, molecular mechanisms underlying the cardiac hypertrophy in HCM and
      DCM will be discussed.

PMID- 10885319
TI  - [Role of cytokine signaling in cardiomyopathy].
AB  - Interleukin (IL)-6-related cytokines share gp130 as the signal-transducing
      protein. Cardiac myocytes produce various kinds of cytokines including IL-6 and
      cardiotrophin-1. Activation of gp130 transduces hypertrophic and cytoprotective
      signals in cardiac myocyte via JAK/STAT, MAP kinase and PI-3 kinase pathways.
      Besides various well-established mechanisms by which myocardial hypertrophy and
      remodeling are regulated, a gp130 signaling may be a newly discovered mechanism
      that regulates these events in association with cytoprotective effect in
      cardiomyopathy. In addition, the activation of gp130 dependent signaling pathway
      in cardiac myocytes might play a pivotal role in the prevention of heart failure.

PMID- 10885320
TI  - [Animal models of cardiomyopathy].
AB  - Animal models of cardiomyopathy have been used in many studies for our
      understanding of the pathophysiology of this disease. Syrian hamster, BIO 14.6,
      one of the most widely used models of cardiomyopathy, was reported to be caused
      by large deletion in the exon 1 and the promoter region of the delta-sarcoglycan
      gene. Cardiac hypertrophy or heart failure has been induced in dogs, rabbits,
      rats and many other animals by various manipulations such as drugs, pressure
      and/or volume overload and chronic rapid pacing. Recently, transgenic or knockout
      mice were examined to investigate the pathogenesis and development of the
      disease. It is important to select appropriate models for the aim of the studies.

PMID- 10885321
TI  - [Diabetology].

PMID- 10885322
TI  - [Development of influenza vaccines against newly emerging A/H5N1 virus].
AB  - Emergence of highly virulent influenza A/H5N1 viruses in Hong Kong in 1997 posed
      a threat of pandemic and brought an urgent need to develop a suitable seed virus
      for vaccine production. The virulence of the H5N1 viruses to chicken embryos
      should hamper the efficient production of the vaccine. In addition, potential
      virulence to humans raised safety issue in manufacturing vaccine. Toward vaccine
      development, one approach is to use an avirulent avian influenza virus
      antigenically similar to the virulent ones as a surrogate vaccine strain. The
      other approach is based on the attenuation of pathogenicity of virulent H5N1
      virus by genetic engineering of the hemagglutinin gene and selection of a gene
      constellation. The reverse genetics technique can make the latter approach
      possible. Candidate strains suitable for vaccine production could be prepared by
      using either approach.

PMID- 10885323
TI  - High-glycemic index foods, hunger, and obesity: is there a connection?
AB  - The relative importance of different dietary causes of obesity remains
      controversial. This review examines whether consumption of high-glycemic index
      (GI) carbohydrates may be a contributing factor. Although data from long-term
      studies are lacking, short-term investigations indicate that consumption of high
      GI carbohydrates may increase hunger and promote overeating relative to
      consumption of items with a lower GI. As long-term research on GI and weight
      regulation accumulates, consumption of whole grain and lower GI cereals instead
      of highly refined cereals is a dietary change that may help prevent overeating
      and is consistent with current dietary guidelines.

PMID- 10885324
TI  - Retinoids, carotenoids, and human breast cancer cell cultures: a review of
      differential effects.
AB  - Cancer of the breast is the most common incident cancer and cause of death from
      cancer in women. Several epidemiologic studies have reported a significant
      inverse relationship between the intake of vitamin A and/or provitamin A-rich
      foods and the incidence of certain cancers, including breast cancer. A large
      number of studies have been conducted to determine the effect of retinoids (all
      trans-retinoic acid, in particular), and to a lesser extent of carotenoids, on
      breast cancer using cell culture models. In general, the results of these studies
      demonstrate beneficial effects of all-trans-retinoic acid on different breast
      cancer cells. This review compares studies conducted in different laboratories
      using retinoids and carotenoids as treatments for breast cancer cells and
      suggests what may be the underlying reasons for the differential effects of these
      compounds on the same cell lines.

PMID- 10885325
TI  - Pro-opiomelanocortin (POMC) deficiency and peripheral melanocortins in obesity.
AB  - Melanocortin peptides, derived from pro-opiomelanocortin (POMC), appear to play a
      significant role in appetite and body weight regulation. Expression of the Pomc
      gene in the central nervous system results in the production of melanocortin
      peptides, which bind to the melanocortin-4 receptor (MC4-R) and inhibit food
      intake. MC4-R knockout mice exhibit adult-onset obesity, whereas MC4-R agonists
      suppress food intake in several models of obesity. Recently, Pomc knockout mice
      were generated and shown to develop hyperphagia and obesity with a time-course
      and severity comparable to MC4-R knockout mice, whereas daily administration of a
      stable alpha-melanocyte stimulating hormone analogue reversed this effect. These
      data clearly implicate POMC peptides and melanocortin receptors in the
      pathophysiology of obesity and provide important new tools for their development
      as therapeutic targets in obesity.

PMID- 10885326
TI  - Is fruit juice a "no-no" in children's diets?
AB  - In addition to milk and other beverages, juices in reasonable quantities (12 fl
      oz/day or less) provide nutrients infants need while keeping sugar and food
      energy intakes adequate.

PMID- 10885328
TI  - Trans fatty acids and plasma lipoproteins.
AB  - Perceptions of the health effects of trans fatty acids, particularly in the form
      of margarine, have undergone several changes during the past 10 years. What was
      once heralded as the healthy alternative to butter now assumes the role of
      coconspirator. A new study finds that consumption of trans fatty acids, such as
      those found in stick margarine and shortening, have negative effects on
      lipoprotein profiles that are comparable to those of saturated fatty acids. In
      the prevention and treatment of cardiovascular diseases, therefore, it is
      recommended that consumers reduce intakes of both saturated and trans fatty
      acids.

PMID- 10885327
TI  - Effect of vitamin E, vitamin C, and beta-carotene on stroke risk.
AB  - In a recent prospective observational study, vitamins C and E and beta-carotene
      did not elicit protective effects on stroke risk. Lutein, however, may elicit
      such protection. Nevertheless, these nutrients may be important modulators of the
      outcome after the occurrence of a stroke. At present, optimal control of the
      classic stroke risk factors in combination with increased consumption of fruits,
      vegetables, and antioxidant nutrients may represent the safest and most efficient
      strategy to control stroke risk.

PMID- 10885329
TI  - [Central nervous system tuberculosis with and without HIV infection--clinical,
      neuroimaging, and neuropathological study].
AB  - Clinical data, neuroimaging, and neuropathology of 17 patients with central
      nervous system tuberculosis were reported. Of this population, 12 were men, 5,
      women; ages ranged from 23 to 75 years (mean, 46.9). There were three HIV
      positive patients among them. More than a half of patients had disturbance of
      consciousness as initial symptom. Neurological signs were variable such as visual
      acuity loss, hemiparesis, paraparesis, cerebellar ataxia, and tremor, though
      disturbance of consciousness was the most frequent (36%). Neuroimaging (X-ray CT
      and MRI) revealed meningeal enhancement (53%), tuberculoma (50%), hydrocephalus,
      infarction or bleeding and spinal cord tuberculoma. There were three patients who
      showed paradoxical progression. Eleven patients were performed CSF examination,
      all of them revealed increased cell count (mean, 206 counts/mm3) and protein
      (mean, 225 mg/dl), but only 4 patients were positive on bacteriological
      examination including PCR. Seven patients died and 5 patients were performed
      autopsy. Neuropathologically, all patients showed a stage of meningitis prominent
      on basal brain (basal cistern and/or Sylvian fissure). Cell infiltrations
      including lymphocyte, monocyte, and eosinocyte were most severe around blood
      vessels, and observed in all cases except one which showed only fibroblast and
      collagen fibers indicating healed stage. In some cases, there existed epithelioid
      cells and Langhans giant cells, and in some cases, fibrin exudate. There were
      three cases having tuberculoma, one HIV case and two non-HIV cases. Center of
      tuberculoma in non-HIV case was formed by caseous necrosis, and tuberculoma was
      surrounded by granuloma constituted by epithelioid cells and Langhans giant cells
      with lymphocyte cell infiltration and proliferation of blood vessels. In
      contrast, tuberculoma of HIV case did not include granuloma, and was formed with
      small cells with large nucleus which surrounded arteries. Our studies, as other
      studies, failed to show any differences between HIV and non-HIV patients
      clinically, as well as on neuroimaging study. But neuropathological study
      suggests that mechanism of tuberculoma formation may be different between in HIV
      positive patients and in non-HIV patients.

PMID- 10885330
TI  - [A case of atopic myelitis].
AB  - A 35-year old woman was admitted to our hospital because of slowly increased
      numbness of lower truncus and the legs for 10 months. She showed atopic
      dermatitis on her nape and bilateral popliteal fossa, and signs and symptoms of
      anorexia nervosa, such as asitia, emaciation, and menopause. Neurologic
      examination revealed Lhermitte's sign, muscle weakness of bilateral hands, deep
      and superficial sensory disturbance below the Th 4 level of thoracic spinal cord,
      and increased tendon reflexes of four limbs. Laboratory data showed hyperIgEemia
      and high titer of mite antigen specific IgE in sera. Cervical MRI demonstrated
      abnormal intensity area located at the C6 to C7 segments (i.e. low intensity in
      T1 weighted images and high in T2). She also showed hypercalcemia and swelling of
      the parathyroid gland, and had been diagnosed primary hyperparathyroidism by
      scintigram of the parathyroid gland. We concluded that this case is thought to be
      atopic myelitis, which has been recently reported as acute myelitis associated
      with hyperIgEemia and atopic dermatitis proposed by Kira et al. (1997). The
      patient also had anorexia nervosa and primary hyperparathyroidism.

PMID- 10885331
TI  - [A case of familial type IIa hypercholesterolemia with the clinical features
      similar to cerebrotendinous xanthomatosis].
AB  - A 63-years-old woman noticed unsteady gait at the age of 56 years and then
      developed dysarthria two years later. A general physical examination at age 56
      revealed mild hypertrophy of both Achilles tendons. On neurological examination,
      she had scanning speech, moderate limb and truncal ataxia, and moderate
      hyperreflexia of all limbs. A soft tissue X-ray examination disclosed hypertrophy
      of both Achilles tendons with multiple punctate calcification. Brain MRI showed
      diffuse cerebellar atrophy. Motor evoked potentials in the right limb disclosed a
      prolonged central conduction time. Blood chemistry showed familial type IIa
      hypercholesterolemia (cholesterol 320 mg/dl, and LDL-cholesterol 245 mg/dl), yet
      cholestanol level was normal. A examination of CTX gene mutation at hot spots
      revealed no mutation. Her mother and two siblings also had hypertrophy of
      Achilles tendons as well as type IIa hypercholesterolemia. In addition, the one
      sibling showed mild ataxia of lower limbs, respectively. This report suggests a
      possible link between familial type IIa hypercholesterolemia and cerebellar
      degeneration syndrome clinically mimicking CTX.

PMID- 10885332
TI  - [A case of severe stenosis of bilateral distal vertebral artery successfully
      treated with anastomosis operation].
AB  - A 65-year-old male complained of loss of consciousness for several minutes,
      transient diplopia and dizziness. He had no neurological deficits nor
      abnormalities in MR imaging. However, flow velocity of bilateral vertebral artery
      on ultrasonography indicated severe stenosis of bilateral distal vertebral
      artery. Brain angiography revealed severe stenosis of bilateral distal vertebral
      artery as well as occlusion of right middle cerebral artery (MCA). Single photon
      emission CT (SPECT: ECD-RVR method with acetazolamide loading) showed decreased
      cerebral blood flow and poor perfusion reserve in bilateral cerebellar hemisphere
      and right MCA territory. Superficial temporal artery-superior cerebellar artery
      (STA-SCA) anastomosis was performed. The patient turned out to have no episodes
      of unconsciousness attack, transient diplopia and dizziness after operation.
      Cerebral blood flow (CBF) in the posterior circulation was also improved.
      Evaluating quantitative CBF measurement by means of ECD-RVR method was useful for
      evaluating CBF. In cases who have severe stenosis of bilateral distal vertebral
      artery with complaints of vertebrobasilar insufficiency, STA-SCA anastomosis may
      be one of the most effective treatments.

PMID- 10885333
TI  - [A case of neuro-Behcet's disease presenting as chronic progressive cerebellar
      ataxia].
AB  - A case of neuro-Behcet's disease manifested as chronic progressive cerebellar
      ataxia is reported. A 56-year-old woman had suffered from recurrent oral aphthous
      ulcers, genital ulcers and polyarthritis since her late twenties. At age 53, she
      noticed small stepped-gait; at age 55, she developed scanning speech, a wide
      based gait and memory disturbance. On admission she had oral aphthous ulcers,
      scarring of genital ulcers and polyarthralgia. A neurological examination
      revealed memory disturbance, saccadic eye movement, scanning speech, a slow
      tongue wiggle, moderate limb and truncal ataxia and moderate hyperreflexia in
      four limbs without pathological reflexes. Relevant laboratory examination data
      showed a positive HLA-B51. The cerebrospinal fluid (CSF) had a mild elevation of
      the cell counts and the amounts of protein. Brain magnetic resonance imaging
      showed mild atrophy of the cerebellum and brainstem. Fluoro-2-deoxyglucose
      positron emission tomography showed a decreased glucose metabolism in the
      cerebellum and brainstem. Methylprednisolone pulse therapy (1 g x 3 days)
      followed by oral corticosteroids (50 mg/day) with gradual tapering markedly
      alleviated the cerebellar ataxia. The presence of oral and genital ulcers and CSF
      pleocytosis as well as effectiveness of corticosteroids in relieving the
      neurologic symptoms suggested neuro-Behcet's disease. We propose the existence of
      a new subtype of neuro-Behcet's disease characterized by chronic progressive
      cerebellar involvement possibly due to microvasculitis for which corticosteroids
      may be effective.

PMID- 10885334
TI  - [A case of hemolytic uremic syndrome caused by verotoxin producing
      enteropathogenic Escherichia coli (O157:H7) with prolonged cerebrovascular
      dysfunction].
AB  - A 56-year-old woman was admitted to our hospital because of bloody watery
      diarrhea. Stool cultures on admission revealed the verotoxin producing
      enteropathogenic Escherichia coli (VTEC) (O157:H7). Hemolytic uremic syndrome
      (HUS) appeared on the 4th hospital day. Plasma exchange was performed from the
      4th day to the 11th day. Mental confusion appeared on the 6th day, and was
      aggravated until the 18th day, and slowly improved afterwards. Serial cranial CT
      in series demonstrated low density areas in the bilateral parietooccipital lobes
      on the 26th day, and the left one diminished but the right one became more
      evident on the 49th day. The series of single photon emission computed topography
      (SPECT) revealed that in the region of the temporoparietooccipital lobe cerebral
      blood flow decreased on the left side on the 30th day, on both sides on the 39th
      day, and on the right side on the 82nd day. There are few reports of prolonged
      cerebrovascular dysfunction observed in serial studies of SPECT in a patient of
      HUS by VTEC (O157:H7). We should be aware, however, of the appearance of the CNS
      involvement in the recovery stage because the prolonged cerebrovascular
      dysfunction may occur as our case.

PMID- 10885335
TI  - [An autopsy case of primary cerebellar-pontine angle epidermoid carcinoma].
AB  - A 65-year-old man developed right facial palsy and six months later experienced
      sudden unconsciousness and right hemiplegia. On admission he had severe nuchal
      rigidity, decreased visual acuity, and a hearing disturbance. A CT scan and
      angiography failed to reveal any lesions in the brain, but CSF cytology showed
      undifferentiated malignant cells with a high level of neuron-specific enolase. A
      postcontrast CT scan and MRI demonstrated diffuse meningeal enhancement and a
      faintly rim-enhanced cystic lesion at the cerebellopontine angle. The patient
      died four months after admission, and postmortem examination revealed meningeal
      dissemination of squamous cell carcinoma, probably arising from an epidermoid
      cyst at the cerebellopontine angle. Microscopic examination revealed squamous
      epithelial debris and a foreign body reaction in portions of the cyst wall and in
      the surrounding subarachnoid space near the base of the cyst. Rim enhancement of
      the cyst on MRI and the microscopic findings indicated that the recurrent
      headaches may have been the result of chemical aseptic meningitis caused by
      spontaneous leakage of the cyst's contents.

PMID- 10885336
TI  - [CNS cryptococcosis with idiopathic CD4+ T lymphocytopenia].
AB  - A 33-year-old Japanese man, with a history of recurrent skin cryptococcosis, was
      admitted complaining of fever and severe headache for 3 weeks. He had no known
      risk factors for human immunodeficiency virus (HIV) infection. Cerebrospinal
      fluid examination revealed an elevated opening pressure of 32 cm H2O, cell counts
      of 884/mm3, a total protein value of 184 mg/dl, a glucose level of 16 mg/dl, and
      demonstrated a positive India ink stain for fungus. Cultures grew Cryptococcus
      neoformans. Hematological studies showed a persistently low CD4+ cell count
      (30/mm3) and a low CD4/CD8 ratio of 0.1. He has been repeatedly seronegative
      (ELISA and Western blot) for HIV-1 and HIV-2. He responded to fluconazole, and
      was given itraconazole as secondary prophylaxis because of persistent low CD4
      counts. To our knowledge this is the first patient with idiopathic CD4+ T
      lymphocytopenia associated with CNS cryptococcosis in Japan. CD4 counts should be
      part of the initial work up for patients with CNS cryptococcosis.

PMID- 10885337
TI  - [A case of HTLV-I associated myelopathy with abnormal patchy MRI lesions in the
      spinal cord].
AB  - We report a case of HTLV-I associated myelopathy (HAM) with a spinal cord MRI
      showing abnormal multifocal and patchy lesions. A 50-year-old woman suffering
      from progressive paraparesis was admitted to our hospital. HTLV-I antibodies in
      the serum and CSF were positive, and a diagnosis of HAM was made. Her T2 weighted
      spinal cord MRI showed scattered areas of high signal intensity from the cervical
      to the thoracic cord. The lesions were enhanced with gadolinium-DTPA on T1
      weighted imaging. Atrophy of the thoracic cord has been reported in many patients
      with HAM. In rare cases, T2 weighed thoracic cord MRI showed diffuse high signal
      intensity. The pattern of high signal intensity in our case, however, was
      multifocal and patchy, thus differing from the findings of previous reports. And
      we believe this is the first such report. This case suggests that the MRI of HAM
      patient may show multifocal and scattered lesions in the spinal cord.

PMID- 10885338
TI  - [Lysosomal glycogen storage disease with normal acid maltase (Danon) without
      apparent cardiomyopathy and mental retardation].
AB  - A 29-year-old male who had a past history of mild ECG abnormality of arrhythmia
      at the age of 14 years, was referred to our hospital because of elevated serum
      creatine kinase (CK) level. He had never been aware of muscular weakness nor
      cardiac symptoms. Neurological examination revealed normal muscle strength of all
      extremities except marked back muscle weakness. He had normal intelligence. On
      laboratory examination, serum AST, ALT, LDH, aldolase, CK and myoglobin levels
      were elevated. Both lactate and pyruvate levels were normally responded after an
      ischemic exercises test. Acid maltase activity was normal in white blood cells. A
      muscle biopsy obtained from rectus femoris muscle revealed vacuolar myopathy with
      mildly increased PAS positive material. On electron microscopy, there were
      autophagic vacuoles scavenging glycogen particles and cytoplasmic debris, and
      sarcolemmal indentation, compatible with the findings of lysosomal glycogen
      storage disease with normal acid maltase. This patient had unusual clinical
      features of absent mental retardation and no apparent cardiomyopathy.
      Accordingly, mental retardation is probably not necessary to see later onset of
      cardiac muscle involvement.

PMID- 10885339
TI  - [A case of multiple sclerosis with hypothalamic amenorrhea].
AB  - We present a 31-year-old woman of multiple sclerosis. At age 28, she was admitted
      with complaints of echolalia and a gradual onset of weakness affecting the right
      upper and bilateral lower limbs. Brain MRI showed high intensity areas in the
      bilateral frontal gyri, lobuli paracentralis, and left anterior thalamus.
      Although she had been in remission for 3 years, she developed dysesthesia of left
      upper and lower limbs. Cervical T2 weighted MRI showed a new high signal
      intensity lesion in the spinal cord from the C2 to C3 level. The combination of
      the cerebral, thalamic and spinal cord lesions with remission and excerbations
      allowed the diagnosis of clinically MS to be made. She suffered amenorrhea from
      the onset of her illness. Serum prolactin was within the normal range. The LH and
      FSH basal secretions were decreased and there were low delayed secretions of LH
      and FSH after intravenous injection of 100 micrograms LHRH. We consider that her
      amenorrhea was caused by the hypothalamic lesion, supported by MR findings of
      dilatation of the third ventricle.

PMID- 10885340
TI  - [A case of Charcot-Marie-Tooth disease 1 B with Val 146Phe mutation of myelin
      protein zero showing a severe clinical phenotype].
AB  - A 15-year-old boy had complaints of progressive gait disturbance and foot
      deformity. He started to walk at the age of 18 months. Since two years of age, he
      had noticed unstable gait. He showed evident scoliosis and enlarged great
      auricular nerves. Moderate to slight degrees of muscular atrophy and weakness of
      distal upper, and proximal and distal lower limbs were observed. Pes equinovarus
      deformity of both feet was obvious. Muscle stretch reflexes were absent in both
      limbs except decreased triceps brachii reflex. Vibratory sensation was decreased
      severely in the toes and mildly in the fingers. In cerebrospinal fluid, protein
      was mildly elevated. Median nerve motor conduction velocity was 5.0 m/sec. On
      sural nerve biopsy, both demyelinated and remyelinated axons and onion-bulbs
      without hypomyelination were observed. Therefore, the diagnosis of Charcot-Marie
      Tooth disease 1 was made. The direct sequencing of the genomic DNA encoding the
      Po gene revealed a mutant allele, a guanine to thymine substitution of nucleotide
      position 436, which caused a substitution of phenylalanine for valine at amino
      acid position 146. This type of Po mutation is different from any type of Po
      mutation reported in the literature.

PMID- 10885341
TI  - [Pontine hemorrhage presenting with Foville syndrome and transient contralateral
      hyperhidrosis].
AB  - This report concerns a 88-year-old diabetic and hypertensive woman with pontine
      hemorrhage who presented with Foville syndrome and contralateral hyperhidrosis.
      She was admitted to our hospital for sudden onset of headaches and disturbed
      consciousness. Neurologic examination revealed bilateral miosis, Foville syndrome
      and superficial hemianesthesia on the right side of the face and body. No
      associated Horner syndrome and other autonomic dysfunction were observed.
      Laboratory data were normal except for diabetic findings. Brain CT and MRI
      revealed a hematoma in the left side at the lower pons. One month after the
      onset, hemihyperhidrosis on the face, arm and upper trunk contralateral side of
      the lesion appeared abruptly, and gradually disappeared a week later. Sweating on
      the ipsilateral side was normal and no new lesion was seen on the brain CT then.
      Only a few cases of contralateral hyperhidrosis due to pontine lesion have been
      reported. We suggest that the contralateral inhibitory sweating pathway was
      disrupted though the ipsilateral excitatory one was intact. Contralateral
      hyperhidrosis attributed to imbalance of the perspiratory control can be observed
      in the subacute or late phase after pontine hemorrhage.

PMID- 10885342
TI  - Depressive symptoms among African American women with HIV disease.
AB  - Depressive symptoms are a common response to HIV disease and evidence suggests
      that women may be at particular risk. Very little of the research on depressive
      symptoms within the context of HIV disease has included women, however, and even
      fewer studies have targeted African American women. In a beginning effort to
      address this gap, the authors performed a secondary analysis of data collected
      from 1992-1995 in a sample of 264 HIV+ women. The purpose of the secondary
      analysis was to describe the levels of depressive symptoms for a subsample of 152
      African American subjects and to identify significant covariates. The original
      analysis was based on a stress and coping framework and was designed to provide a
      description of stressors, resistance factors, and adaptational outcomes of HIV+
      women. It included various measures of psychological distress and quality of
      life. Depressive symptoms were not examined in the original analysis as an
      outcome of HIV disease, however. In the secondary analysis, depressive symptoms
      were operationalized using a depression subscale of the Brief Symptom Inventory
      (BSI) (Deragotis, 1993). Major categories of correlates examined included person
      resources, environmental resources, coping responses, and disease-related
      stressors. The data used in the analysis were collected during the fourth and
      fifth interviews of the longitudinal study, with 152 of the African American
      women having completed both interviews. Variance in depressive symptoms was
      analyzed using ANOVA, zero-order correlations, and multiple regression analysis.
      The mean depressive symptoms score for the subsample of African American women
      was considerably higher than published means for female and male normative
      samples, respectively. The regression model accounted for over half of the
      variance in depressive symptoms (R2 = .515). Significant correlates included self
      esteem, family cohesion, HIV symptoms and quality of life. The findings support
      personal and social resources and disease-related factors as important correlates
      of HIV+ African American women's depressive symptoms and suggest the need for
      interventions to address such factors.

PMID- 10885343
TI  - The long gray tunnel: the day-to-day experience of spouse caregivers of people
      with Alzheimer's disease.

PMID- 10885344
TI  - Determinants of health-promoting behavior among women ages 65 and above living in
      the community.
AB  - This study utilized Pender's Health Promotion Model to investigate through
      canonical correlation analysis the role that select cognitive-perceptual factors
      (health self-determinism, learned helplessness, self-esteem, and perceived
      health) and modifying factors (age, race, marital status, education, and income)
      play in understanding participation of community-living older adult women (age >
      or = 65) in the health-promoting behaviors of health responsibility, physical
      activity, nutrition, spiritual growth, interpersonal relations, and stress
      management. These were measured by the Health-Promoting Lifestyle Profile II in a
      convenience sample of 107 community-living older adult women (mean age 76.7
      years). Gender-specific benefits and barriers to participating in health
      promoting behaviors were also explored using open-ended questions. Two
      significant canonical variates were demonstrated. These indicated that age,
      marital status, race, education, and self-esteem and the two health-related
      factors of perceived health and health self-determinism made statistically
      significant contributions to the health-promoting behaviors of physical activity,
      nutrition, spiritual growth, and interpersonal relations. Benefits identified
      included better psychological well-being, coping with the general issues of
      aging, social interaction, improved function, and management of existing health
      problems. Internal barriers focused on perceived physical difficulties with all
      types of health-promoting behaviors; external barriers included aspects of the
      activity itself, lack of support from others and structural barriers. Study
      results suggest that older adult women (age > or = 65) participate in health
      promoting behaviors for both health enhancement and health management reasons and
      that barriers may be a more important determinant of older women's health
      promoting lifestyle behaviors than previously described in the model.

PMID- 10885345
TI  - When primum non nocere fails.

PMID- 10885346
TI  - Zinc supplementation for infants.

PMID- 10885347
TI  - Prevention of paracetamol poisoning.

PMID- 10885348
TI  - Doctors in the NHS: the restless many and the squabbling few.

PMID- 10885349
TI  - Dressing heart-failure patients on Savile Row--tailored treatment?

PMID- 10885350
TI  - Measurement of lipid-soluble vitamins--further adjustment needed?

PMID- 10885351
TI  - Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or
      BRCA2 mutation.
AB  - BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes highly predispose to
      breast and ovarian cancer. In families with BRCA1 or BRCA2 mutations,
      identification of mutation carriers is clinically relevant in view of the options
      for surveillance and prevention. METHODS: We assessed presymptomatic DNA testing
      and prophylactic surgery in 53 consecutive families presenting to the Rotterdam
      Family Cancer Clinic with a known BRCA1 or BRCA2 mutation. We identified
      predictors for DNA testing and prophylactic surgery with univariate and
      multivariate analysis. FINDINGS: 682 unaffected individuals with a 50% risk (275
      women and 271 men) or with a 25% risk (136 women) for carrying a mutation were
      identified and offered a DNA test. Presymptomatic DNA testing was requested by
      48% (198 of 411) of women and 22% (59 of 271) of men (odds ratio for difference
      between sexes 3.21 [95% CI 2.27-4.51]; p<0.001). In women, DNA testing was
      significantly more frequent at young age, in the presence of children, and at
      high pre-test genetic risk for a mutation. Of the unaffected women with an
      identified mutation who were eligible for prophylactic surgery, 51% (35 of 68)
      opted for bilateral mastectomy and 64% (29 of 45) for oophorectomy. Parenthood
      was a predictor for prophylactic mastectomy but not for prophylactic
      oophorectomy. Age was significantly associated with prophylactic oophorectomy,
      but not with prophylactic mastectomy, although there was a tendency towards
      mastectomy at younger ages. INTERPRETATION: In a clinical setting, we show a high
      demand for BRCA1 and BRCA2 testing by unaffected women at risk, and of
      prophylactic surgery by unaffected women with the mutation. Young women with
      children especially opt for DNA testing and prophylactic mastectomy.

PMID- 10885352
TI  - Zinc supplementation and stunted infants in Ethiopia: a randomised controlled
      trial.
AB  - BACKGROUND: Stunting is highly prevalent in Ethiopia and many other developing
      countries but the reason for it is poorly understood. Zinc is essential for
      growth but diets in such countries often do not contain zinc in sufficient
      quantity or of sufficient bioavailability. Thus zinc deficiency may play a major
      role in stunting. The aim of the study was to investigate whether the low rate of
      linear growth of apparently healthy breastfed infants in a rural village in
      Ethiopia could be improved by zinc supplementation. METHODS: A randomised, double
      blind, placebo-controlled trial was done on apparently healthy breastfed infants
      aged 6-12 months. 100 non-stunted (length-for-age, Z score < -2) were matched for
      age and sex with 100 randomly selected stunted (> -2) infants. Infants, both
      stunted and non stunted, were matched by sex, age (within 2 months) and recumbent
      length (within 3 cm) for random assignment, to receive a zinc supplement (10 mg
      zinc per day, as zinc sulphate) or placebo, 6 days a week for 6 months.
      Anthropometric measurements were taken monthly, data on illness and appetite were
      collected daily, and samples of serum and hair were taken at the end of the
      intervention for the analysis of zinc. FINDINGS: The length of stunted infants
      increased significantly more (p<0.001) when supplemented with zinc (7.0 cm [SE
      1.1]) than with placebo (2.8 cm [0.9]); and the effect was greater (p<0.01) than
      in non-stunted infants (6.6 [0.9] vs 5.0 [0.8] cm for the zinc and placebo groups
      respectively, p<0.01). Zinc supplementation also increased the weight of stunted
      children (1.73 [0.39] vs 0.95 [0.39] kg for the corresponding placebo group,
      p<0.001) and of non-stunted children (1.19 [0.39] vs 1.02 [0.32] kg for the
      corresponding placebo group, p<0.05). Zinc supplementation resulted in a markedly
      lower incidence of anorexia and morbidity from cough, diarrhoea, fever, and
      vomiting in the stunted children. The total number of these conditions per child
      was 1.56 and 1.11 in the stunted and non-stunted zinc supplemented children
      versus 3.38 and 1.64 in the stunted and non-stunted placebo-treated children,
      respectively. At the end of the intervention period, the concentrations of zinc
      in serum and hair of stunted infants, who had not been supplemented with zinc,
      were lower than the respective concentrations of zinc in serum and hair of their
      non-stunted counterparts. INTERPRETATION: Combating zinc deficiency can increase
      the growth rate of stunted children to that of non-stunted infants in rural
      Ethiopia. This would appear to be due, at least in part, to reduction in
      morbidity from infection and increased appetite.

PMID- 10885353
TI  - Diagnostic errors in three medical eras: a necropsy study.
AB  - BACKGROUND: Studies comparing the accuracy of clinical diagnosis in unselected
      patients who died in hospital in different medical eras have shown no decline of
      errors in the main diagnosis. We assessed changes in diagnostic accuracy over 20
      years. METHODS: We analysed retrospectively diagnostic errors, with use of
      necropsy as the gold standard for diagnosis. We randomly selected 300 patients
      who died at a tertiary-care teaching hospital in Switzerland--100 in each of
      1972, 1982, and 1992. We classified discrepancies between clinical diagnosis and
      necropsy findings as major and minor errors. FINDINGS: The overall necropsy rate
      at the hospital stayed at around 90% for the whole period. During the study, the
      frequency of major discrepancies declined significantly (1972, 30%; 1982, 18%;
      1992, 14%; p=0.007). The rate of minor diagnostic errors increased significantly
      from 23% in 1972 to 46% in 1992 (p<0.001). The increase in overall diagnostic
      accuracy occurred mainly because of a significant improvement in specificity for
      cardiovascular diseases (1972, 85%; 1982, 82%; 1992, 97%; p=0.034) and non
      significantly improved sensitivity (1972, 69%; 1982, 82%; 1992, 86%; p=0.061).
      Sensitivity also improved for infectious diseases (1972, 25%; 1982, 67%; 1992,
      86%; p=0.036). Sensitivity and specificity for neoplastic diseases were high
      originally and did not change. The total number of diagnostic procedures per year
      increased from 191 in 1972 to 259 in 1992, mainly because of non-invasive
      techniques, such as ultrasonography, and endoscopies. INTERPRETATION: The
      frequency of major diagnostic errors in unselected patients who died in hospital
      was halved over 20 years, probably because of improved clinical skills and new
      diagnostic procedures.

PMID- 10885354
TI  - Application of viral-load kinetics to identify patients who develop
      cytomegalovirus disease after transplantation.
AB  - BACKGROUND: Cytomegalovirus (CMV) continues to be a major problem post
      transplantation; early markers for predicting patients at risk of CMV disease are
      needed. Peak CMV load in the blood correlates with CMV disease but frequently
      occurs too late to provide prognostic information. METHODS: 359 transplant
      recipients (162 liver, 87 renal, and 110 bone marrow) were prospectively
      monitored for CMV DNA in the blood with qualitative and quantitative PCR. 3873
      samples were analysed. The CMV load in the first PCR-positive sample and the rate
      of increase in CMV load in blood during the initial phase of replication were
      assessed as risk factors for CMV disease using logistic regression. FINDINGS: 127
      of the 359 patients had CMV DNA in the blood and 49 developed CMV disease.
      Initial viral load correlated significantly with peak CMV load (R2=0.47,
      p=<0.001) and with CMV disease (odds ratio 1.82 [95% CI 1.11-2.98; p=0.02; 1.34
      [1.07-1.68], p=0.01, and 1.52 [1.13-2.05], p=0.006, per 0.25 log10 increase in
      viral load for liver, renal, and bone-marrow patients, respectively). The rate of
      increase in CMV load between the last PCR-negative and first PCR-positive sample
      was significantly faster in patients with CMV disease (0.33 log10 versus 0.19
      log10 genomes/mL daily, p<0.001). In multivariate-regression analyses, both
      initial CMV load and rate of viral load increase were independent risk factors
      for CMV disease (1.28 [1.06-1.52], p=0.01, per 0.25 log10 increase in CMV load
      and 1.52 [1.06-2.17], p=0.02, per 0.1 log10 increase in CMV load/mL daily,
      respectively). INTERPRETATION: CMV load in the initial phase of active infection
      and the rate of increase in viral load both correlate with CMV disease in
      transplant recipients; in combination, they have the potential to identify
      patients at imminent risk of CMV disease.

PMID- 10885355
TI  - Relation between agendas of the research community and the research consumer.
AB  - BACKGROUND: Previous studies have suggested that research agendas can be biased.
      To determine whether there is a mismatch between available research evidence and
      the research preferences of consumers we examined research on interventions for
      the treatment of osteoarthritis of the knee joint. METHODS: We searched published
      and unpublished studies on interventions in this condition to assess the
      structure of the evidence base. Focus groups and a postal survey of research
      consumers were then undertaken to examine their views and research priorities.
      FINDINGS: Review of published and unpublished reports showed that the evidence
      base was dominated by studies of pharmaceutical (550, 59%) and surgical (238,
      26%) interventions. 24 (36%) of 67 survey respondents ranked knee replacement as
      the highest priority for research, whereas 14 (21%) chose education and advice as
      their first choice. INTERPRETATION: There is a mismatch between the amount of
      published work on different interventions, and the degree of interest of
      consumers. We suggest that broadening of the research agenda would be more in
      line with current treatment patterns and consumer views. If this mismatch is not
      addressed, then evidence-based medicine will not be representative of consumer
      needs.

PMID- 10885356
TI  - Malaria chemoprophylaxis with tafenoquine: a randomised study.
AB  - BACKGROUND: Tafenoquine is an analogue of primaquine with an improved therapeutic
      and safety profile. It has a long half-life and activity against liver-stage
      malaria parasites, so may be useful for chemoprophylaxis. In this randomised,
      double-blind study we assessed the efficacy and safety of tafenoquine in
      different doses. METHODS: 2144 individuals aged 12-20 years living in Lambarene,
      Gabon, an endemic area for Plasmodium falciparum malaria, were invited to take
      part. 535 attended, and 426 eligible participants were randomly assigned
      tafenoquine (250 mg, 125 mg, 62.5 mg, or 31.25 mg) or placebo daily for 3 days.
      417 received initial curative treatment with halofantrine, and 410 completed the
      assigned prophylaxis regimen. During follow-up of 70 days, adverse events were
      recorded and thick blood smears were examined weekly. The primary and secondary
      endpoints were the number of individuals with positive blood smears by day 56 and
      day 77, respectively. Analyses were per-protocol. FINDINGS: Eight positive blood
      smears were recorded by day 56 (four/82 participants in the placebo group;
      four/79 tafenoquine 31.25 mg group). By day 77, 34 positive blood smears had been
      recorded (14/82 placebo; 16/79 tafenoquine 31.25 mg; three/86 tafenoquine 62.5
      mg; one/79 tafenoquine 125 mg; none/84 tafenoquine 250 mg). Numbers of adverse
      events did not differ significantly between the treatment groups. INTERPRETATION:
      Tafenoquine is effective and well tolerated. It has the potential to replace
      currently used drugs for malaria chemoprophylaxis.

PMID- 10885357
TI  - A toxic testicle.

PMID- 10885358
TI  - Reduction in incidence of severe paracetamol poisoning.
AB  - We report substantial reductions in the frequency of severe paracetamol
      hepatotoxicity locally and nationally after legislative limitations on its sale.
      These reductions were not explained by changes in referral patterns or use of N
      acetylcysteine.

PMID- 10885359
TI  - Change in occurrence of paracetamol overdose in UK after introduction of blister
      packs
AB  - Since the introduction of new regulations that limit the availability of
      paracetamol in the UK, there has been a substantial decrease in the occurrence
      and severity of cases of paracetamol overdose.

PMID- 10885360
TI  - Melanisation of Cryptococcus neoformans in human brain tissue.
AB  - Melanin-specific reagents revealed melanin in cryptococcal cell walls from human
      brain tissue, and fungal-cell melanin "ghosts" were recovered from infected
      tissue. The results indicate that Cryptococcus neoformans melanises during human
      infection.

PMID- 10885362
TI  - Meningococcal disease among children of Indian subcontinent ethnic origin.
AB  - The rate of meningococcal septicaemia and meningitis was significantly lower in
      children of Indian subcontinent ethnic origin than in children of other origins
      over 12 years in the Blackburn area of the UK.

PMID- 10885361
TI  - Survival in beta-thalassaemia major in the UK: data from the UK Thalassaemia
      Register.
AB  - About 50% of UK patients with beta-thalassaemia major die before the age of 35
      years, mainly because conventional iron-chelation therapy is too burdensome for
      full adherence. Patients require an individually-tailored treatment plan
      incorporating new, more tolerable approaches.

PMID- 10885363
TI  - Deaths among heroin users remain a mystery.

PMID- 10885364
TI  - Anti-CD40 allays rheumatoid arthritis in mice.

PMID- 10885365
TI  - Scientific journals online: the debate intensifies.

PMID- 10885366
TI  - Bolivian soldiers double up as health workers.

PMID- 10885367
TI  - E. coli outbreak deaths spark judicial inquiry in Canada.

PMID- 10885368
TI  - Accelerating the development and future availability of HIV-1 vaccines: why,
      when, where, and how?
AB  - An HIV-1 vaccine offers the best long-term hope to control the AIDS pandemic,
      especially in less-developed countries. To ensure its future availability we need
      to increase our research efforts today, including clinical trials. Although small
      scale clinical trials of HIV-1 vaccines have been underway since 1987, the first
      phase III efficacy trials started only recently in the USA and Thailand. Initial
      results from these trials will be available within the next 2-3 years, and we
      must start planning now how vaccines should be used if found to be effective. In
      the meantime, the continuing promotion of the parallel development and assessment
      of other candidate vaccines is important. Financial mechanisms should also be
      developed as an incentive to industry and to ensure equitable distribution of
      future vaccines in less-developed countries. Moreover, a concerted effort is
      needed to ensure the development and future availability of appropriate vaccines
      for Africa.

PMID- 10885369
TI  - The trauma of war in Sierra Leone.

PMID- 10885370
TI  - The damage done to Chechnya's medical establishment.

PMID- 10885371
TI  - The sexual abuse of men in detention in Sri Lanka.

PMID- 10885372
TI  - Aboriginal reconciliation still a long way to go.

PMID- 10885373
TI  - Adjuvant radiotherapy for DCIS.

PMID- 10885374
TI  - Adjuvant radiotherapy for DCIS.

PMID- 10885375
TI  - Adjuvant radiotherapy for DCIS.

PMID- 10885376
TI  - Adjuvant radiotherapy for DCIS.

PMID- 10885377
TI  - Antipsychotic drugs and risk of homicide.

PMID- 10885378
TI  - Acquired syphilitic retinitis and HIV.

PMID- 10885379
TI  - Pneumocystis carinii pneumonia in Malawian children.

PMID- 10885380
TI  - Reversible dementia due to coexisting disease.

PMID- 10885381
TI  - Early diagnosis of invasive aspergillosis.

PMID- 10885382
TI  - Early diagnosis of invasive aspergillosis.

PMID- 10885383
TI  - Mycobacterium tuberculosis transmission and HIV status.

PMID- 10885384
TI  - Mycobacterium tuberculosis transmission and HIV status.

PMID- 10885385
TI  - The ovary: cysts, screening, and tamoxifen.

PMID- 10885386
TI  - The global burden of disease disability weights.

PMID- 10885388
TI  - The Nobel chronicles. 1993: Richard John Roberts (b 1943) Phillip A Sharp (b
      1944).

PMID- 10885387
TI  - Attitudes to compulsory admission in psychiatry.

PMID- 10885389
TI  - Neoadjuvant therapy in the treatment of high risk rectal carcinoma.
AB  - The management of rectal cancer remains a challenging and controversial area of
      surgical oncology. The spectre of local recurrence, with its' poor prognostic and
      palliative outcomes, is known to be highly dependent on operative technique and
      to vary widely between surgeons. The roles of radiotherapy and chemotherapy have
      been the subject of trials for 30 years and yet no consensus on treatment exists.
      In this review article we will summarise the evolution of radiotherapy and
      chemoradiation in the treatment of rectal cancer and evaluate the evidence
      available for the use of "neoadjuvant" chemoradiation. In particular, the role of
      adjuvant therapies in the setting of total mesorectal excision will be discussed.

PMID- 10885390
TI  - Bone metastasis in breast cancer: the role of parathyroid hormone related
      protein.

PMID- 10885391
TI  - Occult breast cancer: a challenge from a surgical perspective.
AB  - Patients with occult breast cancer pose a challenging diagnostic and therapeutic
      problem. High-quality mammography is required to decrease the false-negative
      rates. A number of other imaging methods have been proposed in the diagnostic
      evaluation of these women, including breast ultrasonography, color Doppler
      ultrasonography, breast magnetic resonance imaging (MRI), positron emission
      tomography (PET), and scintimammography. Among them, MRI may be particularly
      helpful, since it has a high sensitivity and may enable preoperative localization
      of the primary, thus allowing the surgeon to perform a breast conserving
      procedure. Treatment options include surgery, radiotherapy and watchful waiting
      (followed by mastectomy when a breast tumor is detected). Systemic therapy is
      usually required in the management of these patients.

PMID- 10885392
TI  - Metastasectomy as a cytoreductive strategy for treatment of isolated pulmonary
      and hepatic metastases from breast cancer.
AB  - The authors sought to examine the utility of resection in conjunction with
      adjuvant chemotherapy for treatment of metastases from breast cancer isolated to
      the liver or lungs. Limitations of regional therapy were examined and potential
      agents for systemic therapy were reviewed. As resection of metastases is a
      controversial therapeutic approach, no clinical trials are available for review.
      Rather, evidence for a potential role for surgery rests on retrospective studies
      of small series of patients. Technical advances have rendered resection of liver
      and lung metastases safe. Long-term results as reported by other investigators
      support the role of metastasectomy in selected patients. The site of failure
      following ablation of liver metastases is usually in the liver. Following
      resection of lung metastases, nonpulmonary and disseminated recurrences are most
      common. Adjuvant therapy with docetaxel or any other agent or combination with
      significant activity against visceral metastases might potentiate long-term
      results.

PMID- 10885393
TI  - Steric effect and effect of metal coordination on the reactivity of nitric oxide
      with cysteine-containing proteins under anaerobic conditions.
AB  - A comparison is made between the reactivity of nitric oxide (NO) with cysteine,
      bovine serum albumin (BSA) and metallothionein-1 (MT1) at pH 7 under strictly
      anaerobic conditions. The rate of reaction of NO with these amino acid/proteins
      was found to be of the order: cysteine > BSA >> MT1, in clear disparity with the
      size of the reactants. The difference in the reaction rates is attributed to
      steric effects due to the high molecular size in the case of BSA and to effects
      of metal coordination proper as well as to steric effects associated with the
      closed dual shell-like structure resulting from the tight coordination of the
      thiolate groups with Zn2+ in MT1. The mechanisms of the reaction of NO with
      cysteine, BSA and MT and its possible implication for the rate of the respective
      reactions are discussed.

PMID- 10885394
TI  - Viscosity analysis of the temperature dependence of the solution conformation of
      ovalbumin.
AB  - The viscosity of ovalbumin aqueous solutions was studied as a function of
      temperature and of protein concentration. Viscosity-temperature dependence was
      discussed on the basis of the modified Arrhenius formula at temperatures ranging
      from 5 to 55 degrees C. The activation energy of viscous flow for hydrated and
      unhydrated ovalbumin was calculated. Viscosity-concentration dependence, in turn,
      was discussed on the basis of Mooney equation. It has been shown that the shape
      parameter S decreases with increasing temperature, and self-crowding factor K
      does not depend on temperature. At low concentration limit the numerical values
      of the intrinsic viscosity and of Huggins coefficient were calculated. A master
      curve relating the specific viscosity etasp to the reduced concentration c[eta],
      over the whole range of temperature, was obtained and the three ranges of
      concentrations: diluted, semi-diluted and concentrated, are discussed. It has
      been proved that the Mark-Houvink-Kuhn-Sakurada (MHKS) exponent for ovalbumin
      does not depend on temperature.

PMID- 10885395
TI  - Reaction of reducing hydroxyl radical adducts of pyrimidine nucleotides with
      riboflavin and flavin adenine dinucleotide (FAD) via electron transfer: a pulse
      radiolysis study.
AB  - Using the techniques of pulse radiolysis with time-resolved spectrophotometric
      detection, it has been demonstrated that the interaction of reducing OH radical
      adducts of dCMP, TMP and UMP with riboflavin (RF) and flavin adenine dinucleotide
      (FAD) does proceed via an electron transfer reaction. From buildup kinetics of
      radical species, the rate constants of electron transfer from reducing OH adducts
      of pyrimidines to RF and FAD have been determined, respectively. It could be
      deduced that RF and FAD would reduce the probability of repair of the damaged DNA
      in the presence of enzymes and antioxidants, accordingly RF and FAD might have a
      radiosensitization effect on DNA damage.

PMID- 10885396
TI  - Heat capacity of hydrogen-bonded networks: an alternative view of protein folding
      thermodynamics.
AB  - Large changes in heat capacity (deltaCp) have long been regarded as the
      characteristic thermodynamic signature of hydrophobic interactions. However,
      similar effects arise quite generally in order-disorder transitions in
      homogeneous systems, particularly those comprising hydrogen-bonded networks, and
      this may have significance for our understanding of protein folding and other
      biomolecular processes. The positive deltaCp associated with unfolding of
      globular proteins in water, thought to be due to hydrophobic interactions, is
      also typical of the values found for the melting of crystalline solids, where the
      effect is greatest for the melting of polar compounds, including pure water. This
      suggests an alternative model of protein folding based on the thermodynamics of
      phase transitions in hydrogen-bonded networks. Folded proteins may be viewed as
      islands of cooperatively-ordered hydrogen-bonded structure, floating in an
      aqueous network of less-well-ordered H-bonds in which the degree of hydrogen
      bonding decreases with increasing temperature. The enthalpy of melting of the
      protein consequently increases with temperature. A simple algebraic model, based
      on the overall number of protein and solvent hydrogen bonds in folded and
      unfolded states, shows how deltaCp from this source could match the hydrophobic
      contribution. This confirms the growing view that the thermodynamics of protein
      folding, and other interactions in aqueous systems, are best described in terms
      of a mixture of polar and non-polar effects in which no one contribution is
      necessarily dominant.

PMID- 10885397
TI  - Spontaneous electrical potential oscillation on a filter impregnated with soybean
      lecithin placed between identical solutions of alanine.
AB  - Filters impregnated with soybean lecithin, placed between two identical aqueous
      alanine solutions, display spontaneous electric potential oscillations. Alanine
      solutions used in a large concentration range from 1 mM to 1 M produce damped
      oscillatory behaviour with an exponential decay in time. The dependence of decay
      time on concentration shows saturation behaviour which is well fitted with a
      sigmoidal curve. Power spectra obtained by Fourier transform show peaks specific
      for each concentration. When fitted with a Lorentzian curve in the peak domain,
      the centre of the peak height and width at half height could be extracted. All
      these parameters depend on alanine concentration in a saturating pattern.

PMID- 10885398
TI  - Quenching mechanism of quinolinium-type chloride-sensitive fluorescent
      indicators.
AB  - Quinolinium based Cl- sensitive fluorescent indicators have been used extensively
      to measure intracellular Cl- activity. To define their fluorescence quenching
      mechanism, a series of N-methyl quinolinium derivatives were synthesized,
      including N-methylquinolinium (Q), 6-methylQ, 6-methoxyQ, 6-chloroQ, 3-bromoQ, 6
      aminoQ and N-methylisoquinolinium. Stern-Volmer plots for quenching by Cl-, Br-,
      SCN-, I-, F-, OAc- and CO3(2-) from both intensity and lifetime measurements were
      linear. Bimolecular quenching rate constants (kq) decreased with increasing anion
      oxidation potentials and increased with increasing quinolinium reduction
      potentials. The free energy change for charge transfer (deltaG), calculated from
      indicator spectral and electrochemical properties, was found to correlate with
      log kq. These results suggest that quenching of quinolinium fluorescence in water
      by anions involves a charge-transfer quenching mechanism. Understanding the
      mechanism facilitates structure-based predictions of the anion sensitivities of
      quinolinium indicators to design improved Cl- indicators with tailored
      properties.

PMID- 10885399
TI  - The positive role of voids in the plasma membrane in growth and energetics of
      Escherichia coli.
AB  - Bacterial respiration, endogenous as well as induced respiration by glucose,
      lactose and glycine betaine, was found to be sensitive to external solute
      concentration. Permeability of hydrogen peroxide, a non-electrolyte of molecular
      size between water and urea, through the bacterial membranes changed directly
      with the rate of respiration (an activity residing in the bacterial plasma
      membrane) in E. coli and the enhanced permeability and respiratory activity were
      highly correlated. Hydrogen peroxide permeability and induction of voids (spaces
      in the matrix of the bilayer into which hydrophobic fluorescent probes partition,
      which in turn were used to assess the modulation of these cavities) were shown to
      be a direct and excellent measure of leak conductance. Fluorescence intensity and
      anisotropy of the extrinsic fluorescent probes (incorporated by growing bacteria
      in their presence) decreased with increased respiration in bacteria, consistent
      with lowered molecular restriction and enhanced hydration in the membrane phase
      for these probes as seen in dimyristoylphosphatidylcholine bilayers due to phase
      transition. The physical basis of osmotic phenomena, as a relevant
      (thermodynamic) volume, could relate to water exchange or compression, depending
      on the osmotic domain. In the domain of compression in bacteria, i.e. well above
      the isotonic range, the computed activation volume was consistent with voids in
      the membrane. This study emphasises a major role of leak conductance in bacterial
      physiology and growth.

PMID- 10885400
TI  - The self-organization of adenosine 5'-triphosphate and adenosine 5'-diphosphate
      in aqueous solution as determined from ultraviolet hypochromic effects.
AB  - The self-association of adenosine 5'-triphosphate (ATP) and of adenosine 5'
      diphosphate (ADP) was studied in aqueous solution at different pH values, over
      the concentration range from 5 x 10(-6) to 5 x 10(-2) M, by ultraviolet
      spectroscopy. Measures of the molar absorptivity of the ultraviolet bands of
      these compounds with increasing concentration have shown two hypochromic effects,
      at concentrations below 10(-3) and above 10(-3) M, respectively. These results
      can be interpreted in terms of self-association processes involving the formation
      of dimers and of polymers. From the fitting of the experimental curves of
      hypochromic effects, self-association constants for dimerization and
      polymerization were calculated. The results obtained are discussed in relation to
      the values reported in the literature and indicate the influence of the
      concentration range not only on the numerical value but also on the order of
      magnitude of the association constants. Comparison of ATP with ADP shows that the
      length of the phosphate chain may be a relevant feature in the nature of the self
      organization processes in these adenine nucleotides in aqueous solution.

PMID- 10885401
TI  - Kinetics of a finite one-dimensional spin system as a model for protein folding.
AB  - Simple spin models are used to analyze the kinetic nature of lowest energy state
      formation of the spin systems as models of protein folding kinetics. The models
      employed in the present paper are based on the spin systems as models of
      biopolymers previously proposed by the author for the analysis of the equilibrium
      nature of transitions [T. Kikuchi, Biophys. Chem. 65 (1997) 109]. In particular,
      the effect of frustrations on the kinetics is investigated with the Monte Carlo
      simulations in this study. The results show that the kinetics of the present
      systems are characterized by the ratio of foldables (pathways on the energy
      landscape that to lead to the lowest energy state) and the temperature dependence
      of the mean first passage time of foldables. We also discuss the free energy
      profile of the present models and the relation of the present results to the
      kinetics of actual proteins.

PMID- 10885402
TI  - Is there a special relationship between CD30-positive lymphoproliferative
      disorders and epidermal proliferation?
AB  - The relationship between CD30+ lymphoma and epithelial proliferations is not well
      defined. CD30+ lymphoma and lymphomatoid papulos (LyP) share immunohistochemical
      epitopes and some other features. A single case of LyP associated with multiple
      keratoacanthomas (KAs) was recently reported. We report two cases of atypical
      lymphocytic proliferation with features of CD30+ lymphoma and LyP intimately
      associated to KA and squamous cell carcinoma (SCC), KA type. This similar
      combination of an epidermal tumor and apparent involvement with atypical
      lymphocytic infiltrates raises the possibility of an association between the two
      entities. We speculate that the association may be more than expected to occur by
      chance and suggest several mechanisms by which the association may evolve.

PMID- 10885403
TI  - Expression of growth hormone receptor in benign and malignant cutaneous
      proliferative entities.
AB  - The skin has the necessary elements to respond to growth hormone (GH) and suffers
      clinical changes in the pathological circumstances of excess and deficiency of
      GH. The GH has been involved in the development of different types of human
      neoplasms. Based on these data, we have studied the GH receptor (GHR) expression
      in acrochordons, seborrheic keratosis, melanocytic nevi, histiocytomas, squamous
      cell carcinomas, basal cell carcinomas, and malignant melanomas by means of the
      immunohistochemistry with the monoclonal antibody MAb 263. All the entities
      showed immunoreactivity for GHR. In the histiocytomas, the expression of GHR in
      the keratinocytes of the hyperplastic epidermis coating the lesion showed a
      strong nuclear pattern, but the non-hyperplastic epidermis of the edges of the
      histiocytomas expressed GHR with a cytoplasmic pattern. In the basal cell
      carcinoma and squamous cell carcinoma, the immunoreactivity was weaker than in
      normal skin. In the squamous cell carcinoma, the intensity of immunostaining
      correlated directly with the grade of cellular differentiation. In conclusion,
      the GH may be involved in the development of different kinds of cutaneous
      neoplasms, and the intracellular localization of GHR may imply a functional
      significance, at least in the histiocytomas.

PMID- 10885404
TI  - bcl-2 protein expression in aggressive and non-aggressive basal cell carcinomas.
AB  - bcl-2, the well known anti-apoptotic gene, cloned more than a decade ago,
      promotes cell viability without promoting cell proliferation. With few
      exceptions, high bcl-2 protein expression is associated with a favourable outcome
      in epithelial tumours. bcl-2 immunoreactivity in basal cell carcinomas (BCCs) is
      contradictory, with 67-100% immunopositivity being reported. Although BCCs are
      traditionally regarded as low-grade, indolent tumours, aggressive BCCs (A-BCCs)
      are mutilative, locally destructive tumours that often recur. bcl-2 protein
      expression as a predictor of BCC aggressiveness is poorly documented in the
      English-language literature. The bcl-2 protein immunoprofile of 50 clinically non
      aggressive (NA-BCCs) and 25 clinically A-BCCs was investigated. Of the latter, 17
      manifested with one, two or three recurrences. bcl-2 protein expression in each
      of the recurrences was also evaluated. bcl-2 expression was scored as follows: 0
      5% positive cells=negative, 6-25%=1+, 26-50%=2+, 51-75%=3+, >75%=4+. "High"
      labeling encompassed 3+ or 4+ labeling while "low" labeling referred to 1 + or 2
      + labeling. Although bcl-2 positivity was noted in all BCCs, low bcl-2 labeling
      was a statistically significant feature of A-BCCs (p < 0.01). High bcl-2 labeling
      of NA-BCCs was a reflection of the bcl-2 labeling of the dominant constituent
      nodular or superficial subtypes. Micronodular BCCs revealed 2+ or 3+ labeling.
      Initial and recurrent A-BCCs with a pure or predominantly infiltrative component,
      demonstrated 1+ or 2+ bcl-2 labeling. The differential bcl-2 expression in the
      various clinicopathological subtypes of BCCs suggests that, despite the common
      derivation of these tumours from a primitive basaloid stem cell and a limited
      potential for metastasis, they form a heterogeneous group of tumours that differ
      markedly in histologic and biological behaviour. While the superficial and
      nodular BCCs are indolent slow-growing tumours with high bcl-2 labeling, the
      aggressive BCCs are infiltrative, desmoplastic tumours with low bcl-2 labeling.
      In mixed tumours, heterogeneity of labeling is a distinctive feature and is
      contributed to in part by the labeling trends of the different histological
      subtypes. The micronodular BCC shows varied bcl-2 labeling but in combined
      tumours occupies a niche intermediate between the non-aggressive nodular and
      superficial and the aggressive infiltrative subtypes. The initial and subsequent
      biopsies of recurrent, adequately excised BCCs share a pure or mixed,
      predominantly infiltrative, stroma-rich histomorphology with low bcl-2 labeling,
      reflecting the immunoprofile of a more aggressive growth pattern.

PMID- 10885405
TI  - Cell proliferation in skin tumors with ductal differentiation: patterns and
      diagnostic applications.
AB  - The kinetic features of skin tumors with ductal differentiation (TDD) remain
      mainly unknown. We selected 88 skin TDD (D-PAS-positive cuticles) classified
      according to Murphy and Elder's criteria. Tumors studied included 13 poromas, 12
      nodular hidradenomas, 10 cylindromas, 6 spiradenomas, 9 syringomas, 9 chondroid
      syringomas, 7 porocarcinomas, 15 malignant nodular hidradenomas, and 7 not
      otherwise specified carcinomas. The same tumor areas were evaluated for mitotic
      figure counting (MFC) and proliferation rate (PR = MIB-1 index), screening 10
      consecutive high-power fields (HPFs) in the most cellular areas. Results were
      recorded by HPF and tumor cellularity, considering both average and standard
      deviation. Differences were analyzed by Student's t-test and analysis of variance
      (ANOVA) and considered significant if p<0.05. PR was significantly higher in
      malignant (23.29 +/- 12.49) than in benign tumors (3.86 +/- 4.44) and in
      poromanodular hidradenoma (4.99 +/- 3.34) than in spiradenoma-cylindroma
      syringoma (1.91 +/- 1.67), but not by malignant tumor type. MFC was significantly
      higher in malignant (25.52 +/- 4.10) than in benign tumors (1.57 +/- 0.38),
      showing porocarcinomas the biggest MFC/10 HPF and malignant nodular hidradenomas
      the highest MFC/1000 cells. PR and MFC are useful malignancy criteria in skin TDD
      and should be evaluated by tumor cellularity to avoid potential
      misinterpretations related with tumor heterogeneity.

PMID- 10885406
TI  - Squamous metaplasia of sebaceous gland.
AB  - Squamous metaplasia in the skin has been reported in the eccrine ducts as eccrine
      squamous syringometaplasia (ESS). To our knowledge, squamous metaplasia of
      sebaceous gland (SMSG) has not been described in human skin. Twenty-two biopsy
      specimens from patients with pressure lesions after cardiac surgery with
      extracorporeal circulation were evaluated for the presence of SMSG. Squamous
      metaplasia of sebaceous gland was identified in five of the eight scalp biopsies
      and none of the buttock biopsies. The squamous metaplasia began in the
      germinative outer layer and advanced in a centripetal way. We believe that SMSG
      is an unspecific change of the sebaceous cells secondary to a chronic injury.
      Ischemia appears to play a mayor role, but other factors such as chronic trauma
      or toxicosis can not be ruled out.

PMID- 10885407
TI  - Silicone granuloma on the entry points of acupuncture, venepuncture and surgical
      needles.
AB  - We describe a case of epithelioid granuloma on the entry points of needles used
      for acupuncture, venepuncture and for taking skin biopsy. The acupuncture needles
      used at each session were silicone coated. Silicon was detected in the vacuoles
      of macrophages and multiple nucleated giant cells by X-ray microanalysis. To our
      knowledge, this is the first case of silicone granuloma arising on the entry
      points of acupuncture, venepuncture and surgical needles.

PMID- 10885408
TI  - Lymphoepithelioma-like carcinoma of the skin: a report of 3 Epstein-Barr virus
      (EBV)-negative additional cases. Immunohistochemical study of the stroma
      reaction.
AB  - Lymphoepithelial carcinoma is a relatively common malignancy in the nasopharynx,
      but it rarely occurs in other sites. We report 3 additional cases of cutaneous
      location. Histopathologically, the tumors consisted of multiple well
      circumscribed dermal-hypodermal nodules composed of aggregates of
      undifferentiated malignant cells. These cells had moderate amounts of
      eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli. There was no
      squamous or glandular differentiation. For each case, a heavy lymphoplasmacytic
      infiltrate was found. No dysplasia was noted in the epidermis. In one case, the
      tumoral component showed numerous Sternberg-like cells scattered within a
      lymphocytic background. This case might be mistaken with a Hodgkin's lymphoma.
      Immunohistochemistry showed that the neoplastic cells were positive for
      cytokeratin and epithelial membrane antigen. In the present report, studying the
      stroma reaction cell components, we have stressed the presence of numerous factor
      XIIIa-positive dendritic cells in 2 cases. Because of the role of these cells in
      the immune response of normal stroma, their presence herein might be in relation
      with the favorable prognosis of this type of primary skin carcinoma. No Epstein
      Barr viral genomic sequences were detected by in situ hybridization. This
      negativity for Epstein-Barr virus may be a help in the differential diagnosis
      from metastatic undifferentiated nasopharyngeal carcinoma.

PMID- 10885409
TI  - Atrophic dermatofibroma. Elastophagocytosis by the tumor cells.
AB  - A 55-year-old woman presented with an asymptomatic red plaque on the left upper
      back for 6 or 7 years. The lesion was depressed in response to finger pressure.
      The clinical diagnosis was anetoderma. Histopathologically, the characteristic
      cells of cellular dermatofibroma proliferated within the thinned dermis, which
      showed atrophy of about 60 or 70%. The proliferated cells were positive for
      factor XIIIa and negative for CD34. The involved dermis showed the loss of
      elastic fibers on elastica van Gieson stain. Electron microscopically, the
      proliferating cells phagocytized the elastic fibers. We report a typical case of
      atrophic dermatofibroma and show the possibility that the cause of this disease
      might be elastophagocytosis between the collagen fibers by the dermatofibroma
      cells.

PMID- 10885410
TI  - Multiple infundibulocystic basal cell carcinomas in association with human
      immunodeficiency virus.
AB  - Infundibulocystic basal cell carcinoma (IBCC) is a relatively recently described
      variant of basal cell carcinoma that is controversial and not universally
      accepted. Excluding cases of nevoid basal cell carcinoma syndrome, IBCC usually
      presents as a small, solitary, superficial lesion on the face of older persons.
      There have been previous reports of diffusely distributed, multiple similar
      lesions, but there is disagreement about the diagnosis in these cases. We present
      a case of a 43-year-old man with multiple papular lesions which we believe
      represent IBCC in the setting of infection with the human immunodeficiency virus
      (HIV).

PMID- 10885411
TI  - Giant-sized condyloma of the breast with focal acantholytic changes.
AB  - BACKGROUND: A healthy 26-year-old pregnant woman presented with a 6.0-cm
      exophytic mass in her left inframammary fold. The lesion was surgically excised.
      METHODS: Histopathologic sections of the skin lesion were reviewed in hematoxylin
      and eosin-stained slides. Additional sections were studied by an in situ
      hybridization method for human papillomavirus DNA (HPV) types 6 and 11. RESULTS:
      The histopathologic examination demonstrated a benign exophytic, verrucous and
      papillary epidermal proliferation with features of condyloma acuminatum.
      Reactivity to HPV DNA types 6 and 11 was demonstrated by in situ hybridization
      method. The epidermis adjacent to, and focally within, the neoplasm showed
      multiple areas of suprabasilar and intraepidermal acantholysis without
      dyskeratosis. CONCLUSIONS: Condylomas related to HPV 6 and 11 may be found in
      extragenital locations including conjunctiva, oral and nasal mucosa. To our
      knowledge, however, the extragenital condylomas described in the literature have
      not included the giant-sized variant. We describe an example of a benign, giant
      sized condyloma acuminatum of the breast with nearby acantholytic alterations
      similar to Hailey-Hailey disease.

PMID- 10885412
TI  - Automatically controlled continuous positive airway pressure. A bright past, a
      dubious future.

PMID- 10885413
TI  - Sleep-related breathing disorders: definitions and measurements.

PMID- 10885414
TI  - Two months auto-adjusting versus conventional nCPAP for obstructive sleep apnoea
      syndrome.
AB  - Autoadjusting nasal continuous positive airway pressure (CPAP) greatly reduces
      the apnoea/hypopnoea index (AHI), and affords a significant reduction in median
      pressure (P50) compared-with manually titrated conventional nasal CPAP. The aim
      of the present study was to test whether these benefits were maintained in the
      medium term at home, in a double-blind crossover study. Ten sequential subjects
      (mean AHI 52.9 x h(-1)) were enrolled. After a manual titration, subjects were
      randomly allocated to 2 months autoadjusting nasal CPAP (AutoSet), followed by 2
      months with the AutoSet device in fixed pressure mode at the manually titrated
      pressure, or vice versa. The machine-scored AHI, P50, and median leak were
      recorded on 12 nights in each arm, and averaged. Mean+/-SEM AHI was 4.0+/-0.3 x
      h(-1) in auto mode, and 3.7+/-0.3 x h(-1) in manual mode (NS). Mean+/-SEM P50 was
      7.2+/-0.4 cmH2O auto, 9.4+/-0.6 cmH2O manual, average reduction 23+/-4%
      (p<0.0001). Auto "recommended" pressure was (mean+/-SEM) 10.1+/-0.5 cmH2O (p=0.04
      with respect to manual) and peak pressure typically 1 cmH2O higher. Median (+/
      SEM) leak was 0.181+/-0.006 L x s(-1) auto (and uncorrelated with AHI or
      pressure), 0.20+/-0.006 L x s(-1) manual (p=0.003). Compliance was 6.3+/-0.4 h in
      auto mode and 6.1+/-0.5 h in fixed mode (NS). Apnoea/hypopnoea index during 2
      months of home autoadjusting nasal continuous positive airway pressure is
      comparable to that during conventionally titrated fixed pressure continuous
      positive airway pressure, while affording a 23% reduction in median pressure but
      no increase in compliance. Leak did not importantly affect autoadjustment.

PMID- 10885415
TI  - External nasal dilation reduces snoring in chronic rhinitis patients: a
      randomized controlled trial.
AB  - Chronic rhinitis patients often suffer from unrefreshing sleep and snoring,
      related to increased nasal resistance to airflow. Previous trials based on
      subjective assessment of snoring have demonstrated beneficial effects of Breathe
      Right (BR), a noninvasive external nasal dilator. Polysomnography (PSG) was
      applied to objectively assess the effects of BR on snoring. Twelve nonobese
      chronic rhinitis patients participated in the present study, which had a
      randomized, placebo-controlled design. The presence of snoring and the absence of
      sleep apnoea was demonstrated during a baseline overnight sleep study. Patients
      were then randomized for placebo or true nasal dilator treatment, which was also
      assessed by overnight PSG. The use of BR had no effect on sleep quality, arousal
      index apnoea-hypopnoea-index or snoring loudness. Snoring frequency was
      significantly lowered by BR (173+/-29 snores x h(-l)), compared with placebo
      (258+/-34 snores x h(-1); p=0.016). The results support the hypothesis that
      Breathe Right is effective in reducing the amount of snoring in patients with
      chronic rhinitis. This objective finding is in line with some other reports on
      subjective improvement of snoring, based upon the judgement of bedpartners.

PMID- 10885416
TI  - Respiratory and upper airways impedance responses to methacholine inhalation in
      spontaneously breathing cats.
AB  - The upper airways may contribute to the increase in respiratory resistance
      induced by methacholine (Mch). The aim of this study was to simultaneously assess
      the Mch response of upper airways and lower respiratory resistances (Rua, Rrs,lo)
      and reactances (Xua, Xrs,lo), and to test whether the change of total respiratory
      resistance and reactance after Mch were affected by upper airways mechanisms.
      Seven cats breathing spontaneously were studied under chloralose, urethane
      anaesthesia. Forced oscillations were generated at 20 Hz by a loud-speaker
      connected to the pharyngeal cavity. A pneumotachograph was placed between rostral
      and caudal extremities of the severed cervical trachea. Pressure drops were
      measured across the upper airways and across the lower respiratory system. Rua,
      Xua, Rrs,lo and Xrs,lo were obtained after nebulized normal saline and Mch
      administered directly through the tracheostomy. The analysis focused on Mch tests
      showing clear positive upper airways response. Volume and flow dependence of
      Rrs,lo and Rua were assessed during tidal inspiration using multiple linear
      regression analysis. After Mch, Rrs,lo increased and became negatively volume
      dependent, while the increase in Rua was associated with no significant change in
      volume dependence; Xrs,lo became negative while Xua did not change. The upper
      airways response to methacholine may thus contribute to the increase in total
      respiratory resistance but may not account for either its negative volume
      dependence or the decrease in total resistance. It is surmised that these
      features more specifically reflect alterations in respiratory mechanics occurring
      at the level of the intrathoracic airways.

PMID- 10885417
TI  - The current single exhalation method of measuring exhales nitric oxide is
      affected by airway calibre.
AB  - The authors have observed that some patients with acute exacerbations of asthma
      do not have substantially higher levels of exhaled nitric oxide (NO). The study
      examined whether this could be explained by the effect of airway calibre on
      exhaled NO. Exhaled NO, height and forced expiratory volume in one second (FEV1)
      were measured in 12 steroid-naive asthmatics and 17 normal subjects. For
      comparison, another group of patients with airways disease (34 cystic fibrosis
      patients) were also studied. In 20 asthmatics (on various doses of inhaled
      steroids, 0-3,200 microg x day-1), exhaled NO was measured before and after
      histamine challenge (immediately after reaching the provocative concentration
      causing a 20% fall in FEV1) and in 12 of these patients, also after nebulized
      salbutamol to restore FEV1 to baseline. Studies were also conducted to examine
      possible confounding effects of repeated spirometry (as would occur in histamine
      challenge) and nebulized salbutamol alone in exhaled NO levels. Exhaled NO was
      measured using a single exhalation method with a chemiluminescence analyser at a
      constant flow rate and mouth pressure. There was a significant correlation
      between FEV1 and exhaled NO in steroid naive asthmatics (r=0.9, p<0.001) and
      cystic fibrosis patients (r=-0.48, p<0.05) but not in normal subjects (r=-0.13,
      p=0.61). Exhaled NO decreased significantly after histamine challenge and
      returned to baseline after bronchodilation by nebulized salbutamol (mean+/-SEM:
      23.6+/-3.6 parts per billion (ppb) (prehistamine), 18.2+/-2.7 ppb (posthistamine)
      and 23.6+/-3.8 ppb (postsalbutamol) p=0.001). Repeated spirometry and nebulized
      salbutamol did not affect exhaled NO measurements significantly. Exhaled nitric
      oxide levels appear to be lower in circumstances of smaller airway diameter.
      Hence, within a subject nitric oxide levels may be artefactually decreased during
      bronchoconstriction. This may be caused by increased airflow velocity in
      constricted airways when the exhalation rate is kept constant.

PMID- 10885418
TI  - Bronchial angiogenesis in severe glucocorticoid-dependent asthma.
AB  - To examine the role of the bronchial microvasculature and adhesion molecule
      expression in severe asthma, the authors have performed an immunohistochemical
      study on bronchial biopsies comparing 15 glucocorticoid-dependent asthmatics, 15
      mild asthmatics and eight control subjects. Serially cut glycol methacrylate
      embedded sections were stained with monoclonal antibodies identifying the vessel
      marker EN-4, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion
      molecule (VCAM)-1, E- and P-selectin. Sections were also stained for lymphocyte
      function associated antigen (LFA)-1 and very late antigen (VLA)-4. By comparison
      with mild asthma and nonasthma, severe asthma was characterized by increased
      numbers of submucosal vessels (p=0.009) which was associated with increased
      numbers of vessels expressing ICAM-1 (p=0.005). A highly significant correlation
      was found between the total number of EN-4+ vessels and the vessels expressing
      ICAM-1 (r=0.85, p=0.01). In contrast, E-selectin expression was lower in severe
      as compared with mild asthma (p=0.01) but not different from normal. No
      differences were found between the three groups in the expression of VCAM-1 and P
      selectin nor in numbers of LFA-1+ and VLA-4+ cells. The results of this study
      support the notion that mucosal neovascularization is an important feature of
      airways remodelling in severe asthma. This is associated with a relatively higher
      density of vessels expressing intercellular adhesion molecule-1, although the
      expression of this adhesion molecule per vessel was not raised.

PMID- 10885419
TI  - Smoking status, disease duration, and educational level in females, are related
      to asthma school participation.
AB  - Limited data is available on those who do not want to attend an asthma school.
      Two hundred and forty-five asthmatics aged 18-65 yrs with an FEV1 >50% predicted
      who had been seen at our outpatient asthma clinic within the last 3 yrs were
      invited to participate in an asthma school. The patients were contacted by phone
      by a nurse, offered a 2 day asthma school without personal costs. Altogether 78%
      of those contacted answered positively. In a logistic regression analysis
      including sex, age, smoking status, educational level, asthma duration and own
      opinion of the disease, the-adjusted odds ratio (OR) for nonsmokers wanting to
      participate versus smokers was 4.0 (95% confidence interval (CI): 1.8-8.3). The
      corresponding figure for patients with a recent asthma attack was 3.4 (95% CI:
      1.5-7.6) compared to those without. For every 10 yr duration of disease the OR
      for wanting to take part in the asthma school increased by 1.6 (95% CI: 1.0-2.3).
      When analysing males and females separately, highly educated females were less
      willing to take part, while an opposite tendency was present in males. In
      conclusion those interested in taking part in an asthma school were characterized
      by highly motivated nonsmokers with long duration of disease and with a recent
      asthma attack, and not being highly educated females.

PMID- 10885420
TI  - Effects of two types of training on pulmonary and cardiac responses to moderate
      exercise in patients with COPD.
AB  - The effects of two 8-week programmes of exercise reconditioning on the time
      constants (tau) of the pulmonary gas exchange, ventilatory and heart rate
      responses to moderate intensity exercise in patients with chronic obstructive
      pulmonary disease (COPD) were studied. Thirty-five subjects (mean+/-SD 64+/-5
      yrs; forced expiratory volume in one second (FEV1) 1.09+/-0.17 L; 41+/-6.2%
      predicted) were randomly assigned either to supervised (s) training on a
      treadmill, 4 days x week(-1) (group S; n=21) or self-monitored (SM) walking 3 or
      4 km in 1 h 4 days x week(-l) (group SM; n=20). The different levels of
      supervision resulted in a different estimated intensity of training (35+/-10 W in
      the SM group and 70+/-22 W in the S group). The kinetics were evaluated with a
      constant-load exercise test on a cycle-ergometer at a work rate corresponding to
      80% the highest oxygen consumption (V'O2) that can be achieved without blood
      lactic acidosis (V'O2,LAT) or 50% of V'O2,max, if maximum oxygen consumption
      V'O2,LAT was not found. Mean endurance time at a work rate equivalent to 70% of
      the pretraining V'O2,max increased by 493+/-281 s in the S group and 254+/-283 s
      in the SM group (p<0.001). Mean tauV'O2 decreased from 83+/-17 s to 67+/-11 s
      (p<0.0001) in the S group and from 84+/-12 to 79+/-16 (p=0.04) in the SM group.
      Mean tau for carbon dioxide output minute ventilation and heart rate were also
      speeded after training, again more markedly in the S group. In the S group there
      was a significant correlation between the decrease in tauV'O2 and the increase in
      endurance time (r=-0.56, SEM=0.21). It is concluded that training speeds the
      kinetic response of oxygen consumption, carbon dioxide production, minute
      ventilation and heart rate to moderate exercise and that the effect is greater
      after supervised, more intense training.

PMID- 10885421
TI  - Effect of lung volume on the oesophageal diaphragm EMG assessed by magnetic
      phrenic nerve stimulation.
AB  - Previous studies have shown conflicting results on the effect of lung volume on
      the diaphragm compound muscle action potential (CMAP). Consequently, the ability
      to quantify the oesophageal diaphragm electromyography (EMG) has been questioned.
      If lung volume changes have little effect on the diaphragm CMAP the accurate
      measurement of voluntary EMG, as an index of respiratory drive, may be possible.
      Furthermore, the measurement of CMAP could provide useful clinical information
      when evaluating patients with neuromuscular disease. To reassess the effect of
      lung volume on the oesophageal diaphragm CMAP, six normal subjects were studied
      using an oesophageal catheter incorporating seven electrodes (number one being
      proximal and seven distal) that were 1 cm in length and 1 cm apart. Electrode
      number three was positioned at the centre of the electrically active region of
      the diaphragm (EARdi) at functional residual capacity (FRC). The diaphragm CMAP
      elicited by bilateral magnetic stimulation of the phrenic nerves was
      simultaneously recorded from four electrode pairs. Pair one was created from
      electrodes one and three, pair two from electrodes two and four, pair three from
      electrodes three and five, and pair four from electrodes five and seven. Phrenic
      nerve stimulation was at residual volume (RV), FRC, FRC+1.0 L, FRC+2.0 L, and
      total lung capacity (TLC). The CMAP recorded from pair one was least influenced
      by changes in lung volume and the amplitude was 2.41+/-0.39 (mean+/-SD), 2.60+/
      0.27, 2.64+/-0.29, and 2.71+/-0.45 mV at RV, FRC, FRC+1.0 L and FRC+2.0 L,
      respectively. At TLC the CMAP was more variable. The CMAP amplitude recorded from
      pair two increased with increasing lung volume and at FRC+2.0 L was 3.7 times
      larger than that at FRC. Pair four usually recorded substantially smaller CMAPs
      at all lung volumes. This study shows that the diaphragm compound muscle action
      potential recorded from an oesophageal electrode just above the diaphragm is
      relatively stable over the lung volume range residual volume to functional
      residual capacity+2.0 L.

PMID- 10885422
TI  - MEKC of desmosine and isodesmosine in urine of chronic destructive lung disease
      patients.
AB  - Degradation of extracellular matrix components is central to many pathological
      features of chronic destructive lung disorders. Desmosine and isodesmosine are
      elastin-derived cross-linked amino acids whose urine levels are considered
      representative of elastin breakdown. The aim of this study was to apply a novel
      methodology, based on high-performance capillary electrophoresis, to the
      quantification of desmosine and isodesmosine in 11 patients with stable chronic
      obstructive pulmonary disease (COPD), 10 with an exacerbation of COPD, nine with
      alpha1-antitrypsin deficiency, 13 with bronchiectasis, and 11 adults with cystic
      fibrosis, in comparison to 24 controls. It was found that, in patients with
      stable COPD, urinary desmosine levels were higher than in controls (p=0.03), but
      lower than in COPD subjects with an exacerbation (p< or =0.05). The highest
      desmosine levels were found in subjects with alpha1-antitrypsin deficiency,
      bronchiectasis and cystic fibrosis (p<0.001 versus stable COPD). In a short-term
      longitudinal study, five stable COPD patients showed a constant rate of desmosine
      excretion (mean coefficient of variation <8% over three consecutive days). In
      conclusion, the present method is simple and suitable for the determination of
      elastin-derived cross-linked amino acid excretion in urine, giving results
      similar to those obtained using other separation methods. In addition, evidence
      is presented that urinary desmosine excretion is increased in conditions
      characterized by airway inflammation, such as exacerbations of chronic
      obstructive pulmonary disease, bronchiectasis and cystic fibrosis. Results
      obtained in subjects with alphal-antitrypsin deficiency suggest that this method
      might be used to evaluate the putative efficacy of replacement therapy.

PMID- 10885423
TI  - Airway inflammation following exposure to diesel exhaust: a study of time
      kinetics using induced sputum.
AB  - The adverse health effects of particulate matter pollution are of increasing
      concern. In a recent bronchoscopic study in healthy volunteers, pronounced airway
      inflammation was detected following exposure to diesel exhaust (DE). The present
      study was conducted in order to evaluate the time kinetics of the inflammatory
      response following exposure to DE using induced sputum from healthy volunteers.
      Fifteen healthy nonsmoking volunteers were exposed to DE particles with a 50% cut
      off aerodynamic diameter of 10 microm 300 microg x m(-3) and air for 1 h on two
      separate occasions. Sputum induction with hypertonic saline was performed 6 and
      24 h after each exposure. Analyses of sputum differential cell counts and soluble
      protein concentrations were performed. Six hours after exposure to DE, a
      significant increase was found in the percentage of sputum neutrophils (37.7
      versus 26.2% p=0.002) together with increases in the concentrations of
      interleukin-6 (12.0 versus 6.3 pg x mL(-1), p=0.006) and methylhistamine (0.11
      versus 0.12 microg x L(-1), p=0.024). Irrespective of exposure, a significant
      increase was found in the percentage of sputum neutrophils at 24 as compared to 6
      h, indicating that the procedure of sputum induction itself may change the
      composition of sputum. This study demonstrates that exposure to diesel exhaust
      induces inflammatory response in healthy human airways, represented by an early
      increase in interleukin-6 and methylhistamine concentration and the percentage of
      neutrophils. Induced sputum provides a safe tool for the investigation of the
      inflammatory effects of diesel exhaust, but care must be taken when interpreting
      results from repeated sputum inductions.

PMID- 10885424
TI  - Transforming growth factor-beta1 is a potent inhibitor of secretory leukoprotease
      inhibitor expression in a bronchial epithelial cell line. Munich Lung Transplant
      Group.
AB  - Obliterative bronchiolitis (OB) is the major long-term complication following
      lung and heart-lung transplantation. In bronchoalveolar lavage fluid samples
      obtained from patients suffering from OB, a marked increase in the number of
      neutrophils and elevated expression of transforming growth factor (TGF)-beta1 had
      been found. The goal of the study was to evaluate whether TGF-beta1 is capable of
      interfering with the expression of the secretory leukoprotease inhibitor (SLPI),
      the dominating defence of the conducting airways against neutrophil elastase
      (NE). The authors analysed the effects of TGF-beta1 on gene expression and
      protein release of SLPI by cultured human bronchial epithelial (BEAS-2B) cells.
      SLPI protein levels in the supernatants were quantified with a specific enzyme
      linked immunosorbent assay; SLPI messenger ribonucleic acid (mRNA) levels were
      measured by reverse transcriptase polymerase chain reaction. Incubation with TGF
      beta1 induced a marked decrease in SLPI protein levels (1 ng x mL(-1) TGF-beta1:
      stimulation index (SI; protein: relation to SLPI protein release of resting
      cells)=0.56; 10 ng x mL(-1) TGF-beta1: SI=0.48; 50 ng x mL(-1) TGF-beta1:
      SI=0.37, p<0.01 each) and mRNA expression (1 ng x mL(-1) TGF-beta1: SI (SI mRNA:
      relation to SLPI mRNA expression of resting cells)=0.46; 10 ng x mL(-1) TGF
      beta1: SI=0.31; 50 ng x mL(-1) TGF-beta1: SI=0.18, p<0.01 each) in a dose
      dependent fashion. Simultaneous incubation of BEAS-2B cells with TGF-beta1 and NE
      also caused a significant reduction in SLPI synthesis (10 ng x mL(-1) TGF-beta1 +
      7.5 U x mL(-1) NE: mRNA SI=0.61, p<0.05; protein SI=0.65, p<0.05; 50 ng x mL(-1)
      TGF-beta1 + 7.5 U x mL(-1) NE: mRNASI=0.52, p<0.05; protein SI=0.58, p<0.05; 10
      ng x mL(-1) TGF-beta1: mRNA SI=0.33, p<0.01; protein SI=0.38, p<0.01). In
      conclusion, the data suggest that the coincidence of neutrophilia and
      upregulation of transforming growth factor-beta1 in obliterative bronchiolitis
      may lead to uninhibited neutrophil elastase activity by downregulation of
      secretory leukoprotease inhibitor, with the consequence of ongoing injury to the
      epithelium.

PMID- 10885425
TI  - Tight junction properties of the immortalized human bronchial epithelial cell
      lines Calu-3 and 16HBE14o-.
AB  - Tight junctions (TJs) make a vital contribution to the barrier properties of the
      airway lining. Opening of TJs, or their frank cleavage, is suspected as a
      pathophysiological event in the lung, but research into the cellular and
      molecular mechanisms involved has been impeded by technical limitations of
      available experimental models. The authors have compared the properties of two
      epithelial cell lines derived from bronchial epithelium to explore whether these
      cell lines could constitute appropriate tools for the study of TJ regulation in
      bronchial epithelium. Investigations of TJs in 16HBE14o- cells and Calu-3 cells
      were made by fluorescent antibody labelling in conjunction with wide-field,
      confocal or 2-photon molecular excitation microscopy (2PMEM). The presence of TJ
      proteins was confirmed by immunoblotting and functional properties of the
      monolayers were studied by measurements of transepithelial electrical resistance
      and mannitol permeability. Cells of both lines formed confluent monolayers in
      which the cells expressed the TJ proteins occludin and ZO-1 in continuous
      circumferential patterns suggestive of functional TJs. This interpretation was
      supported by the development of transepithelial electrical resistances and of low
      paracellular permeability to solutes. Within the limits of resolution offered by
      2PMEM, occludin and ZO-1 appeared to colocalize at TJs. These studies suggest
      that the 16HBE14o- cells and Calu-3 cell lines are potentially useful in vitro
      models to study how tight junction opening or cleavage changes the functional
      barrier properties of bronchial epithelium.

PMID- 10885426
TI  - Tissue factor pathway inhibitor expression by human pleural mesothelial and
      mesothelioma cells.
AB  - The mesothelial lining of the pleura and malignant mesothelioma promote fibrin
      deposition in pleural injury or neoplasia via expression of tissue factor (TF).
      It was hypothesized that these cells might also regulate intrapleural coagulation
      by elaborating TF pathway inhibitor (TFPI). TFPI activity and antigen in pleural
      fluids were assayed from patients with congestive heart failure (CHF), pneumonia,
      empyema, metastatic pleural cancer and malignant mesothelioma. The authors also
      assessed expression of TF and TFPI messenger ribonucleic acid (mRNA) as well as
      TFPI activity and antigen by human pleural mesothelial cells, malignant
      mesothelioma cells (MS-1 cell line) and human lung fibroblasts.
      Immunohistochemical analyses of normal, fibrotic, and neoplastic pleura were
      performed to determine whether TFPI antigen was expressed in vivo. The study
      revealed that TFPI was present in transudates from patients with CHF and
      exudative pleural effusions from patients with pneumonia, empyema or pleural
      carcinoma. TFPI mRNA, activity and antigen were expressed by pleural mesothelial
      cells, MS-1 cells and lung fibroblasts. Cytokines and serum stimulated a
      significant early increase in TF mRNA levels with minimal enhancement of TFPI
      mRNA, activity and antigen levels. TFPI antigen was found in normal, fibrotic and
      neoplastic pleural tissues. The current observations indicate that tissue factor
      pathway inhibitor is locally expressed in pleural disease, but that it does not
      prevent the development of a prothrombotic environment favouring local fibrin
      deposition in pleural inflammation or cancer.

PMID- 10885427
TI  - Neutrophils released from the bone marrow by granulocyte colony-stimulating
      factor sequester in lung microvessels but are slow to migrate.
AB  - Inflammatory mediators such as granulocyte colony-stimulating factor (G-CSF)
      release polymorphonuclear leukocytes (PMNL) from the bone marrow. This growth
      factor is used to promote the host response to infection but its effect on the
      behaviour of leukocytes at the inflammatory site is unclear. This study examined
      the sequestration and migration of PMNL released from the bone marrow by G-CSF in
      a model of streptococcal pneumonia. Eight hours following the administration of
      either human G-CSF (n=6) or saline (n=3) in rabbits, a focal Streptococcus
      pneumoniae pneumonia was induced and the animals were followed for 2 h. The
      thymidine analogue 5'-bromo-2'-deoxyuridine (BrdU) was used to label PMNL
      (PMNL(BrdU)) in the marrow and as a marker of PMNL newly released by the bone
      marrow. The PMNL(BrdU) in the lung and blood were identified using
      immunohistochemistry. G-CSF pretreatment elevated the circulating PMNL (3.6+/-0.4
      (mean+/-SEM) to 8.3+/-1X10(9) x L(-1), p<0.05) and PMNL(BrdU) (5.4+/-2.1 to
      12.5+/-3.1%, p<0.05) counts at 8 h with little further increase caused by the
      subsequent 2 h pneumonia. These counts did not change in the control group.
      Morphometric studies of the lung showed that the total number of PMNL sequestered
      in lung capillaries were increased in the G-CSF group and the percentage of the
      these PMNL that were BrdU-labelled, was higher than in circulating blood
      (p<0.05). In the G-CSF group, only 11.2+/-2.6% of the PMNL that migrated into the
      airspaces were PMNL(BrdU) compared to 50.8+/-8% PMNL(BrdU) in the pulmonary
      capillaries. In vitro studies showed PMNL(BrdU) released from the bone marrow by
      G-CSF are less deformable than unlabelled circulating PMNL (p<0.01). It is
      concluded that granulocyte colony-stimulating factor treatment causes the marrow
      to release polymorphonuclear leukocytes that preferentially sequester in lung
      microvessels but are slow to migrate out of the vascular space into the airspace
      at the pneumonic site.

PMID- 10885428
TI  - Mast cells correlate with angiogenesis and poor outcome in stage I lung
      adenocarcinoma.
AB  - Angiogenesis is in part related to mast cells. However, the biological
      significance of mast cells within lung carcinoma remains unclear.
      Immunohistochemistry was used to stain for tryptase, CD34 and vascular
      endothelial growth factor (VEGF) in 85 cases of stage I nonsmall cell lung
      carcinoma. VEGF was found in 33 of 53 adenocarcinomas and 14 of 32 squamous cell
      carcinomas. Cases of adenocarcinoma had significantly higher mast cell counts
      than those of squamous cell carcinoma. In adenocarcinoma, mast cell counts in
      VEGF-positive tumours were significantly higher than in VEGF-negative tumours,
      whereas in squamous cell carcinoma they were not. Good correlation was observed
      between intratumoural mast cell counts and microvessel counts. Double staining
      showed most intratumoural mast cells expressed VEGF. Importantly, only in lung
      adenocarcinoma, members in the high mast cell count group had significantly worse
      prognosis than those in the low mast cell count group. It is concluded that
      tumour-released vascular endothelial growth factors may be related to mast cell
      accumulation, intratumoural mast cells may produce vascular endothelial growth
      factor, and stromal mast cells correlate with angiogenesis and poor outcome in
      stage I lung adenocarcinoma.

PMID- 10885429
TI  - Moment ratio analysis of multiple breath nitrogen washout in infants with lung
      disease.
AB  - Measurement of lung volumes at end expiratory level and assessment of ventilation
      inhomogeneity is important for respiratory management in infants with lung
      disease. This study compared multiple breath nitrogen washout was compared with
      body plethysmography to measure functional residual capacity in infants and
      assessed ventilation inhomogeneity using mean dilution numbers and alveolar based
      gas dilution numbers. Measurements were performed in 23 infants with lung
      disorders, eleven had wheezing bronchitis, four bronchopulmonary disease, and
      eight cystic fibrosis. Mean age was 11.2+/-5.8 months. Functional residual
      capacity of nitrogen washout (29.8+/-11.4 mL x kg(-1)) was significantly (p<0.05)
      lower than the plethysmographically measured functional residual capacity (40.3+/
      11.4 mL x kg(-1)). Tidal volumes before nitrogen washout (90.4+/-35.1 mL) were
      significantly larger than at the end of the washout (72.2+/-26.9 mL). Alveolar
      based gas dilution numbers (6.7+/-2.3) were significantly lower (p<0.001) than
      mean dilution numbers (10+/-5.7). Functional residual capacity determination by
      nitrogen washout and plethysmography in infants with lung disease showed evidence
      of air trapping and ventilation inhomogeneity. Ventilation inhomogeneities are
      best described by alveolar based dilution numbers, since rebreathing of 100%
      oxygen changes ventilation pattern.

PMID- 10885430
TI  - Management of acute childhood asthma: a prospective multicentre study.
AB  - Children with acute asthma account for a significant proportion of paediatric
      hospital admissions, and clear guidelines exist for their care. The aim of this
      study was to determine their management in the UK. Over 1 year (February 1995 to
      January 1996), children aged 1-14 yrs admitted with acute asthma were studied in
      both teaching and district general hospitals. An admission pro forma was used to
      collect data prospectively, with a computer-based information management system
      for the input of admissions in each centre. Ten centres collected data
      prospectively, with 1,578 admissions involving 1,352 children (median age 3.6
      yrs). Sixty two per cent of children were <5 yrs of age. Sixty three per cent of
      admissions had initial arterial oxygen saturation (Sa,O2) recorded, and, in those
      older than 5 yrs, 36% had their initial peak expiratory flow rate recorded.
      Systemic steroids were given to 78%. An initial Sa,O2 of <92% was associated with
      a longer stay in hospital, and also with intravenous treatment. Preventative
      treatment increased from 42% on admission to 53% on discharge. The rates of
      documented education were low. This is the largest UK study following publication
      of national guidelines and shows that there is still room for improvement in the
      management of children admitted with acute asthma.

PMID- 10885431
TI  - Serial antinuclear antibodies titre in pleural and pericardial fluid.
AB  - The antinuclear antibodies (ANA) test has been a cornerstone of the evaluation of
      connective tissue disease. The aim of this study was to investigate the
      diagnostic value of the ANA test in pleural or pericardial effusions of unknown
      causes. Over a 3-yr period, a total of 126 pleural fluid and 30 pericardial fluid
      samples were analysed. ANA tests were performed using a commercially available
      kit. The ANA kit used an indirect immunofluorescent antibody method with a human
      epithelial (HEP-2) cell line as substrate. Patients with high fluid ANA titre
      (>1:160) received a second aspiration 2 weeks after the initial aspiration if
      diagnosis was not confirmed. ANA results were positive in 39 pleural and 10
      pericardial fluid samples. All but one of the effusions with positive ANA testing
      were exudative. Eleven pleural or pericardial effusions due to active systematic
      lupus erythematosus were identified and all had high ANA titres (1:160) with
      various staining patterns. Thirty-eight of 145 patients (26%) with effusions of
      nonlupus aetiologies had positive ANA testing in pleural or pericardial fluid.
      Thirteen of these 38 patients had high ANA titre. Malignant or paramalignant
      effusions constituted 11 of the 13 samples. In conclusion, although a negative
      antinuclear antibodies test makes a diagnosis of lupus serositis unlikely, high
      antinuclear antibodies titres in pleural or pericardial fluid are not diagnostic
      of lupus serositis even when as high as 1:5,120. An unexplained high antinuclear
      antibodies titre in pleural or pericardial effusion warrants search for
      malignancy.

PMID- 10885432
TI  - Simple method for alpha1-antitrypsin deficiency screening by use of dried blood
      spot specimens.
AB  - The use of dried blood spot (DBS) specimens in quantitative alpha1-antitrypsin
      (alpha1-AT) detection or genetic analysis is limited because protein levels in
      the samples are low and they contain components that can interfere with
      polymerase chain reaction amplification. A methodological adaptation was
      developed to overcome these drawbacks which is discussed here. The study
      population consisted of 200 healthy volunteers and 300 patients with chronic
      obstructive pulmonary disease (COPD). DBS specimens were tested for alpha1-AT
      concentration using a modified nephelometric assay and phenotyped with an
      isoelectric focusing method. Genetic diagnosis was established by
      deoxyribonucleic acid sequencing using a simple purification procedure to remove
      contaminants. The nephelometric method showed a detection limit of 0.284 mg x dL(
      1), corresponding to a serum concentration of 13 mg x dL(-1). The correlation
      coefficient between alpha1-AT concentrations in DBS versus serum samples was
      R2=0.8674 (p<0.0001). All 200 healthy individuals had DBS alpha1-AT
      concentrations >1.9 mg x dL(-1), corresponding to 114 mg x dL(-1) in serum
      samples. One hundred and twenty-five COPD patients (42%) showed alpha1-AT values
      <1.8 mg x dL(-1). Twenty patients with the PIZ phenotype had alpha1-AT values
      lower than 0.64 mg x dL(-1). On the basis of genotyping, one COPD patient was
      classified as heterozygous (PIMM(heerlen)). Selective elution of contaminants
      resulted in optimal alpha(1)1-antitrypsin genotyping. Because of its sensitivity
      and excellent correlation with the standard method, the dried blood spot
      quantitative assay is a reliable tool for routine measurement of alpha1
      antitrypsin.

PMID- 10885433
TI  - Safety of sputum induction in chronic obstructive pulmonary disease.
AB  - The aim of the present study was to evaluate the safety of sputum induction in
      patients with varying severity of chronic obstructive pulmonary disease. The
      subjects were 28 smokers with baseline forced expiratory volume in one second
      (FEV1) of (mean and range) 1.8 (0.8-2.9) L that is 53 (28-69)% of the predicted
      and reversibility of 2.5 (-7.4-9.9)%. Sputum was induced after premedication with
      200 microg salbutamol at increasing concentrations (0.9, 3, 4, and 5%) of
      hypertonic saline nebulized by an ultrasonic nebulizer. The procedure was well
      tolerated, and none of the patients reported major side-effects. However, the
      mean change from prebronchodilator FEV1 during induction was -8.5 (-23-11)%,
      p=0.001, and from postbronchodilator FEV1 -10.7 (-25-5)%, p<0.0001. Three (11%)
      of the patients had a fall in FEV1 from the prebronchodilator baseline of >20%,
      and a further 10 (36%) had a fall of 10-20%. Patients with greater reversibility
      in airway obstruction seemed to get the best benefit from the bronchodilator
      pretreatment, since there was an inverse relationship between reversibility in
      FEV1 and fall in FEV1 during induction (r=-0.4, p=0.03). It is concluded that
      sputum induction by hypertonic saline inhalation can cause meaningful
      bronchoconstriction in patients with chronic obstructive pulmonary disease,
      despite pretreatment with an inhaled beta2-agonist. The results highlight the
      importance of monitoring spirometry during sputum induction to detect
      bronchoconstriction.

PMID- 10885434
TI  - Second messengers, ion channels and pharmacology of airway smooth muscle.
AB  - The airway smooth muscle cell is the chief effector cell governing the control of
      airway calibre in the human lung. The contractile state of the airway smooth
      muscle cell is predominantly influenced by the balance of constrictor and
      relaxant stimuli. Agents such as histamine and acetylcholine cause airway smooth
      muscle cells to contract through activation of specific cell surface receptors
      and engagement of signal transduction pathways and/or ion channels. The
      predominant pathway mediating constriction is activation of phospholipase C, with
      release of inositol 1,4,5-triphosphate and elevation of intracellular calcium
      levels. Relaxation is brought about predominantly by stimulation of adenylyl
      cyclase-coupled receptors (e.g. the beta2-adrenoceptor) resulting in elevation of
      cell cyclic adenosine monophosphate content. Complex crosstalk occurs between
      both of these pathways and also ion channels expressed on the airway smooth
      muscle cell membrane, leading to careful regulation of airway smooth muscle tone.
      A greater understanding of the mechanisms governing control of these pathways
      will lead to the identification of novel therapeutic targets which will in turn
      lead to new agents for the treatment of asthma.

PMID- 10885435
TI  - "Difficult-to-treat" asthma-like symptoms in a 12-yr-old atopic female.

PMID- 10885436
TI  - Reference value of six-minute walking distance in healthy middle-aged and older
      subjects.

PMID- 10885437
TI  - Alexander Pope (1688-1744): his spinal deformity and his doctors.

PMID- 10885438
TI  - UV-induced immune suppression and sunscreen.
AB  - Sun protection factor (SPF) that measures sunscreen protection against erythema
      and edema may not be enough to measure a sunscreen's activity against many other
      biologic reactions induced by ultraviolet radiation (UV). It may be better to
      evaluate sunscreen efficacy using various tools including immune protection
      factor (IPF), mutation protection factor (MPF) and protection against
      photocarcinogenesis. In terms of immune protection, sunscreens protected against
      UV-induced immune suppression significantly. But protection in some cases was
      partial and often the IPF of sunscreens were less than the SPF. IPF may differ
      with various immunological endpoints, and it may be better to use a couple of
      different assays to measure sunscreen protection more objectively. Sunscreen use
      protects against most UV-induced non-melanoma skin cancers and actinic keratoses
      but its activity against melanoma is not clear. More studies with broad-spectrum
      stable sunscreens and better models for the investigation of malignant melanoma
      are required.

PMID- 10885439
TI  - The effect of whole-body sunbed ultraviolet A exposure on the pharmacokinetics of
      the photolabile drug nifedipine.
AB  - The calcium antagonist nifedipine absorbs ultraviolet A (UVA) radiation and
      readily photodegrades in vitro to a toxic nitroso-pyridine photoproduct. We
      examined whether whole body exposure of normal subjects to sunbed UVA radiation
      would affect the pharmacokinetics of nifedipine. Eight healthy, male, Caucasian
      volunteers (phototypes I-III) participated in this ethically approved,
      randomised, cross-over study. Each subject attended on 2 occasions, one week
      apart, and on each occasion was given a single oral dose (10 mg) of nifedipine
      following which blood samples were collected at 0, 0.5, 1. 1.5, 2, 2.5, 3, 3.5,
      4, 5, 6 and 7 h. During one of the visits, 15 min after nifedipine ingestion, a
      whole-body UVA (sunbed comprising Philips R-UVA lamps) dose of 70% of the
      individual's predetermined minimal phototoxic dose was delivered over a period of
      17-36 min. Plasma nifedipine levels were measured using a standard reverse-phase
      high-performance liquid chromatography method. The area under the plasma
      concentration-time curve (AUC) of nifedipine during the UVA irradiation session
      (median 206 ng x ml(-1) x h(-1)) was significantly higher than during the non
      irradiation control session (median 174.5 ng x ml(-1) x h(-1)) (P=0.03; 95% C.I.
      for difference in medians 9.9 to 55.9 ng x ml(-1) x h(-1)). UVA irradiation did
      not significantly affect any of the other measured pharmacokinetic parameters
      (Cmax, t 1/2, tmax). We demonstrate that sunbed UVA irradiation does not lead to
      in vivo photodegradation of nifedipine in healthy humans after a single dose. The
      apparent increase in AUC during UVA irradiation may be due to slightly slower
      metabolism of nifedipine in the presence of toxic photoproduct(s) or due to blood
      distribution changes affecting liver blood flow.

PMID- 10885440
TI  - Photosensitivity to lomefloxacin. A clinical and photobiological study.
AB  - Photosensitivity is an uncommon but characteristic side effect of quinolones,
      with a variable incidence for the different drugs. Several cases, considered
      either phototoxic or photoallergic, have been described with lomefloxacin use.
      During the last 4 years we studied 8 patients (mean age 69.4 years) with
      eczematous or acute sunburn-like lesions in photo-exposed areas, after taking
      lomefloxacin for a period of one week to several months. After drug withdrawal
      and systemic and/or topical corticosteroids, lesions cleared within one week to
      two months, with dischromia in one patient. Six to eight weeks thereafter, a
      photobiological study was performed. Minimal erythema dose (MED) for UVA and UVB
      were normal and photopatch tests with lomefloxacin, ofloxacin, ciproflaxacin and
      norfloxacin, tested at 1%, 5% and 10% in petrolatum and irradiated with 5 and 10
      J/cm2 UVA were negative in 7 patients and 20 controls. Patient 1 had a positive
      photopatch test with lomefloxacin. One patient, who inadvertently reintroduced
      the drug before photopatch testing, developed a sharply limited erythematous
      reaction at 48 h in all irradiated areas, without aggravation at the sites of the
      quinolones patches. Our patients illustrate the polymorphism of clinical
      photosensitivity to lomefloxacin and represent the largest series in which
      photobiological studies have been performed. As in previous reports there are
      arguments favouring photoallergy, but phototoxicity appears to be the main
      mechanism of photosensitivity to quinolones, particularly in older patients with
      concomitant diseases and long-term use of the drug.

PMID- 10885441
TI  - Increased phototoxicity of hydrochlorothiazide by photodegradation.
AB  - The photodegradation products of hydrochlorothiazide produced by ultraviolet (UV)
      radiation were investigated for their phototoxicity utilizing the photohemolysis
      and Candida albicans tests. Hydrochlorothiazide was irradiated for 30, 60, 90 and
      120 min with a 250 W xenon arc lamp using a WG295 cut-off filter. Irradiation of
      hydrochlorothiazide resulted in the gradual decrease of all three absorption
      bands (225, 270 and 320 nm), the blue shift of the 225 nm band, and the
      appearance of a new band around 290 nm. Since previous results demonstrated that
      photosubstitution of chloride could occur, the main product of this photolysis
      most likely is ethoxyhydrochlorothiazide. The photohemolysis test revealed a
      significant increase in photohemolysis observed in the photodegradation products
      produced after 60, 90 and 120 min of UV irradiation. This increase in hemolysis
      value directly correlated with the UV-irradiation time. However, there was no
      significant phototoxic killing of yeast in the Candida albicans test. This
      suggests photodegradation products of hydrochlorothiazide may play an important
      role in phototoxicity by acting on the cell membrane, but not on DNA. Considering
      the high in vitro phototoxicity observed in bendroflumethiazide and the data
      presented here, substitution of chloride seems to be responsible for the
      increased phototoxicity of hydrochlorothiazide.

PMID- 10885442
TI  - Effect of topical application of Hypericum perforatum extract (St. John's wort)
      on skin sensitivity to solar simulated radiation.
AB  - St. John's wort (Hypericum perforatum) is a tradional folk remedy that is used
      for the topical treatment of superficial wounds, scars and burns. A
      characteristic metabolite of St. John's wort is the photodynamic active plant
      pigment hypericin. It is known that hypericin may cause a severe photodermatitis
      called hypericism when higher amounts of St. John's wort are ingested orally. To
      date, no reports on the photosensitizing capacity of topical application of St.
      John's wort are available. Here, we investigated the effects of Hypericum oil
      (hypericin 110 microg/mL) and Hypericum ointment (hypericin 30 microg/mL) on skin
      sensitivity to solar simulated radiation. Sixteen volunteers of the skin types II
      and III were tested on their volar forearms with solar simulated radiation for
      photosensitizing effects of Hypericum oil (n=8) and Hypericum ointment (n=8). The
      minimal erythema dose (MED) was determined by visual assessment, and skin
      erythema was evaluated photometrically. With the visual erythema score, no change
      of the MED could be detected after application of either Hypericum oil or
      Hypericum ointment (P>0.05). With the more sensitive photometric measurement, an
      increase of the erythema-index after treatment with the Hypericum oil could be
      detected (P< or =0.01). The results do not provide evidence for a severe
      phototoxic potential of Hypericum oil and Hypericum ointment, detectable by the
      clinically relevant visual erythema score. However, the trend towards increased
      photosensitivity detected with the more sensitive photometric measurement could
      become relevant in fair-skinned individuals, in diseased skin or after extended
      solar irradiation.

PMID- 10885443
TI  - The effect of PUVA on langerhans cells in rat oral epithelium photosensitized
      with systemic methoxsalen or topical trioxsalen.
AB  - BACKGROUND/PURPOSE: Ultraviolet-A radiation (UVA) of the oral mucosa after
      photosensitization with either systemic methoxsalen (8-MOP) or topical trioxsalen
      (TMP), i.e. mouth-PUVA, has been reported to be successful in the treatment of
      oral lichenoid lesions. In the case of PUVA treatment of skin disorders, local
      immune suppressive effects have been demonstrated, and the antigen presenting
      epithelial Langerhans cells (LCs) have been shown to be especially sensitive to
      ultraviolet treatments. Our aim was to compare the photobiological effects of
      PUVA in oral mucous membrane (OMM) using topical TMP or systemic 8-MOP
      photosensitization. METHODS: Rat OMM photosensitized with topical TMP or systemic
      8-MOP was treated with PUVA using UVA doses of 1-8 J/cm2. The LCs were
      demonstrated in epithelial sheets of the treated OMM with ATPase staining.
      RESULTS: Both treatments caused a sim ilar, dose-dependent depletion of ATPase
      positive LCs, with a maximal depletion of 80% or 73% with 8 J/cm2 at 2 days after
      irradiation as photosensitized with TMP or 8-MOP, respectively. This contrasts
      with earlier published findings in human skin, where topical TMP is an order of
      magnitude greater a sensitizer than 8-MOP, and PUVA-induced depletion of LCs
      occurs maximally 5 days after irradiation. CONCLUSION: The depletion of LCs of
      rat OMM after PUVA treatment is greater using topical TMP compared to systemic 8
      MOP, but the difference is significantly smaller than reported earlier in human
      skin.

PMID- 10885444
TI  - Field-based measurements of personal erythemal ultraviolet exposure through a
      common summer garment.
AB  - The research in this paper quantifies the solar erythemal UV exposures to the
      skin through a common summer garment during outdoor activities. The erythemal
      exposures under the garment for the wet white garment exceeded a MED (minimum
      erythemal dose) at some anatomical sites in summer for a two-hour period. An
      erythemal exposure of 1.7 MED, in excess of the occupational limit for UV
      exposure, was measured under the white garment during swimming for a one-hour
      period. Clothing must form an important component of a UV protection strategy.
      However, it must be realised that total UV protection is not provided and
      significant UV exposures may be received beneath the garment, particularly for a
      white garment in the wet state. This re-enforces the necessity of a combination
      of several UV prevention strategies to minimise UV exposure.

PMID- 10885445
TI  - Parental sun protection management in preschool children.
AB  - A total of 287 children (5 to 8 years old) were investigated for parental sun
      protection management techniques in a questionnaire-based survey. We evaluated
      the parents' knowledge about the risk of melanoma, their level of education,
      their nationality and the child's skin type with the children's use of sunscreen,
      clothes and shade. In general, the parents' knowledge about the correlation of
      skin cancer with extensive sun exposure in childhood was good. There was no
      correlation between the level of parental education and the frequency of sun
      protection measures. Children of non-German parents had significantly less sun
      protection. Our results indicate the need for special teaching programs for
      children in Germany to achieve a more responsible sun protection management.

PMID- 10885447
TI  - Morphological and cytochemical characteristics of periodontal Ruffini ending
      under normal and regeneration processes.
AB  - Current knowledge on the Ruffini endings, primary mechanoreceptors in the
      periodontal ligament is reviewed with special reference to their cytochemical
      features and regeneration process. Morphologically, they are characterized by
      extensive ramifications of expanded axonal terminals and an association with
      specialized Schwann cells, called lamellar or terminal Schwann cells, which are
      categorized, based on their histochemical properties, as non-myelin-forming
      Schwann cells. Following nerve injury, the periodontal Ruffini endings of the rat
      incisor ligament can regenerate more rapidly than Ruffini endings in other
      tissues. During regeneration, terminal Schwann cells associated with the
      periodontal Ruffini endings migrate into regions where they are never found under
      normal conditions. Also during regeneration, alterations in the expression level
      of various bioactive substances occur in both axonal and Schwann cell elements in
      the periodontal Ruffini endings. Neuropeptide Y, which is not detected in intact
      periodontal Ruffini endings, is transiently expressed in their regenerating
      axons. Growth-associated protein-43 (GAP-43) is expressed transiently in both
      axonal and Schwann cell elements during regeneration, while this protein is
      localized in the Schwann sheath of periodontal Ruffini endings under normal
      conditions. The expression of calbindin D28k and calretinin, both belonging to
      the buffering type of calcium-binding proteins, was delayed in periodontal
      Ruffini endings, compared to their morphological regeneration. As the importance
      of axon-Schwann cell interactions has been proposed, further investigations are
      needed to elucidate their molecular mechanism particularly the contribution of
      growth factors during the regeneration as well as development of the periodontal
      Ruffini endings.

PMID- 10885446
TI  - Contaminants in the Canadian Arctic: 5 years of progress in understanding
      sources, occurrence and pathways.
AB  - Recent studies of contaminants under the Canadian Northern Contaminants Program
      (NCP) have substantially enhanced our understanding of the pathways by which
      contaminants enter Canada's Arctic and move through terrestrial and marine
      ecosystems there. Building on a previous review (Barrie et al., Arctic
      contaminants: sources, occurrence and pathways. Sci Total Environ 1992:1-74), we
      highlight new knowledge developed under the NCP on the sources, occurrence and
      pathways of contaminants (organochlorines, Hg, Pb and Cd, PAHs, artificial
      radionuclides). Starting from the global scale, we examine emission histories and
      sources for selected contaminants focussing especially on the organochlorines.
      Physical and chemical properties, transport processes in the environment (e.g.
      winds, currents, partitioning), and models are then used to identify, understand
      and illustrate the connection between the contaminant sources in industrial and
      agricultural regions to the south and the eventual arrival of contaminants in
      remote regions of the Arctic. Within the Arctic, we examine how contaminants
      impinge on marine and terrestrial pathways and how they are subsequently either
      removed to sinks or remain where they can enter the biosphere. As a way to focus
      this synthesis on key concerns of northern residents, a number of special topics
      are examined including: a mass balance for HCH and toxaphene (CHBs) in the Arctic
      Ocean; a comparison of PCB sources within Canada's Arctic (Dew Line Sites) with
      PCBs imported through long-range transport; an evaluation of concerns posed by
      three priority metals--Hg, Pb and Cd; an evaluation of the risks from artificial
      radionuclides in the ocean; a review of what is known about new-generation
      pesticides that are replacing the organochlorines; and a comparison of natural
      vs. anthropogenic sources of PAH in the Arctic. The research and syntheses
      provide compelling evidence for close connectivity between the global emission of
      contaminants from industrial and agricultural activities and the Arctic. For semi
      volatile compounds that partition strongly into cold water (e.g. HCH) we have
      seen an inevitable loading of Arctic aquatic reservoirs. Drastic HCH emission
      reductions have been rapidly followed by reduced atmospheric burdens with the
      result that the major reservoir and transport agent has become the ocean. In the
      Arctic, it will take decades for the upper ocean to clear itself of HCH. For
      compounds that partition strongly onto particles, and for which the soil
      reservoir is most important (e.g. PCBs), we have seen a delay in their arrival in
      the Arctic and some fractionation toward more volatile compounds (e.g. lower
      chlorinated PCBs). Despite banning the production of PCB in the 1970s, and
      despite decreases of PCBs in environmental compartments in temperate regions, the
      Arctic presently shows little evidence of reduced PCB loadings. We anticipate a
      delay in PCB reductions in the Arctic and environmental lifetimes measured in
      decades. Although artificial radionuclides have caused great concern due to their
      direct disposal on Russian Shelves, they are found to pose little threat to
      Canadian waters and, indeed, much of the radionuclide inventory can be explained
      as remnant global fallout, which was sharply curtailed in the 1960s, and waste
      emissions released under license by the European reprocessing plants. Although Cd
      poses a human dietary concern both for terrestrial and marine mammals, we find
      little evidence that Cd in marine systems has been impacted by human activities.
      There is evidence of contaminant Pb in the Arctic, but loadings appear presently
      to be decreasing due to source controls (e.g. removal of Pb from gasoline) in
      Europe and North America. Of the metals, Hg provokes the greatest concern;
      loadings appear to be increasing in the Arctic due to global human activities,
      but such loadings are not evenly distributed nor are the pathways by which they
      enter and move within the Arctic well understood.

PMID- 10885448
TI  - Scanning electron microscopic studies of the vascular smooth muscle cells and
      pericytes in the rat heart.
AB  - The cytoarchitecture of smooth muscle cells and pericytes in the rat cardiac
      vessels was studied by scanning electron microscopy after the removal of
      connective tissue matrices using a modified KOH-collagenase digestion method. The
      initial stem of the coronary arteries had groups of smooth muscle cells which ran
      in various directions on the outermost layer of the media. Although smooth muscle
      cells in coronary arteries of more than 100 microm in the outer diameter were
      arranged in a rough circle around the vessel axis, oblique and/or longitudinal
      muscle bundles were often present in the medio-adventitial border of the vessels.
      The presence of irregularly oriented muscular bundles is probably connected with
      resistance against the stretching force induced by the beating of the heart. As
      the vessel size decreased toward the periphery, almost all of the smooth muscle
      cells became spindle-shaped with several tiny processes and ran circularly or
      helicaly to the vessel axis. In the precapillary arterioles (6-12 microm), smooth
      muscle cells acquired various cytoplasmic processes which helicaly surrounded
      endothelial cells. Unmyelinated nerves were often associated with arterioles.
      Blood capillaries were morphologically divided into three segments: arterial
      capillaries which had pericytes with wide and circularly oriented processes, true
      capillaries whose pericytes extended long and thin primary processes bilaterally
      along the vessel axis, and venous capillaries surrounded irregularly and loosely
      by wide pericytic processes. The stellate pericytes in the postcapillary venules
      (10-30 microm) gradually changed into flat tape-like smooth muscle cells, which
      ran circularly in the collecting venules and veins (30-200 microm). The large
      collecting veins were finally overwhelmed by superficial thin layer of the
      myocardium, their own smooth muscle cells being very sparse. This suggests that
      large veins have poor ability to contract by themselves but are influenced by the
      surrounding myocardial cells.

PMID- 10885449
TI  - The subfibrillar arrangement of corneal and scleral collagen fibrils as revealed
      by scanning electron and atomic force microscopy.
AB  - The present study was designed to analyze the subfibrillar structure of corneal
      and scleral collagen fibrils by scanning electron microscopy (SEM) and atomic
      force microscopy (AFM). Isolated collagen fibrils of the bovine cornea and sclera
      were fixed with 1% OsO4, stained with phosphotungstic acid and uranyl acetate,
      dehydrated in ethanol, critical point-dried, metal-coated, and observed in an in
      lens type field emission SEM. Some isolated collagen fibrils were fixed with 1%
      OsO4, dehydrated, critical point-dried and observed without metal-coating in an
      AFM. Isolated collagen fibrils treated with acetic acid were also examined by SEM
      and AFM. SEM and AFM images revealed that corneal and scleral collagen fibrils
      had periodic transverse grooves and ridges on their surface; the periodicity
      (i.e., D-periodicity) was about 63 nm in the cornea and about 67 nm in the
      sclera. Both corneal and scleral collagen fibrils contained subfibrils running
      helicoidally in a rightward direction to the longitudinal axis of the fibril; the
      inclination angle was about 15 degrees in the corneal fibrils and 5 degrees in
      the scleral fibrils. These findings indicate that the different D-periodicity
      between corneal and scleral fibrils depends on the different inclinations of the
      subfibrils in each fibril. The present study thus showed that corneal collagen
      fibrils differ from scleral collagen fibrils not only in diameter but also in
      substructure.

PMID- 10885450
TI  - Histometrical and three-dimensional analyses of liver hematopoiesis in the mouse
      embryo.
AB  - The development and cytoarchitectures of liver hematopoiesis in the mouse from 10
      to 19 days of gestation were examined by light and electron microscopy. In fetal
      liver hematopoiesis, four stages were identified: Stage I, the onset of
      hematopoiesis at 10 days; Stage II, expansion of the volume of the hematopoietic
      compartment at 11 and 12 days; Stage III, the peak in the volume of the
      hematopoietic compartment at 13 and 14 days; and Stage IV, the involution of
      hematopoiesis after 15 days. During Stages I-II, hematopoietic stem cells
      appeared to move from the sinusoidal lumina into primitive hepatic cell cords
      through the sinusoidal endothelium to give rise to colonies among hepatoblasts.
      At Stage III, the hematopoietic colonies formed ellipsoidal foci as a structural
      unit of hematopoiesis. These foci were 35-70 x 20-40 microm in size, and
      erythroblastic islands could be observed in the center of each. Each island
      contained central macrophages surrounded by a ring of erythroblasts. The
      macrophages underwent mitosis, showing close contact with the erythroblasts,
      after which the hematopoietic foci appeared as cords. At Stage IV, these cord
      shaped hematopoietic foci became disrupted, and round solitary foci including
      macrophages appeared within the hepatic cell cords on meandering sinusoids. In
      fetal liver hematopoiesis, macrophages could be one of the major cell components
      comprising the hematopoietic microenvironment, especially at Stages II and III.

PMID- 10885451
TI  - Semiquantitative morphological analysis of stromal cells in the irradiated and
      recovering rat thymus.
AB  - To understand the roles of thymic stromal cells in T-lymphocyte development, we
      semiquantitatively analysed rat thymi recovering from irradiation (6 Gy), using a
      transmission electron microscope. The most striking findings were that the
      percentage of subcapsular epithelial cells significantly increased in the cortex
      on day 3 after irradiation compared with the control; the percentage of
      intermediate epithelial cells significantly increased in the cortex on days 3 and
      5 after irradiation and in the medulla on days 5 and 7 compared with the control;
      the interdigitating cells disappeared from the medulla by day 7 after irradiation
      and reappeared on day 9. The present data thus reveal that during recovery after
      irradiation (6 Gy), marked changes occur in the relative proportions of different
      epithelial cell subtypes in the cortex and medulla of the rat thymus. In
      addition, the percentages of macrophages and interdigitating cells also changed
      during the recovery. These changes, which may be associated with the abrupt
      proliferation of thymocytes after irradiation, should shed light on the
      significance of stromal cells in the T cell development.

PMID- 10885452
TI  - Phenotypical and morphological analyses of intraepithelial and lamina propria
      lymphocytes in normal and regenerating gastric mucosa of rats in comparison with
      those in intestinal mucosa.
AB  - While the intestine has abundant intraepithelial lymphocytes (IELs) including
      extrathymically differentiated T-cell populations and natural killer (NK) cells,
      the stomach contains only a few IELs. To elucidate whether the gastric epithelium
      is capable of inducing predominant lymphocyte lodging and subsequent
      differentiation within, we counted the number of IELs and lamina propria
      lymphocytes (LPLs) and calculated the percentage of IELs to total lymphocytes for
      each alpha-beta T cell, gamma-delta T cell, CD4+ cell, CD8+ cell and NK cell in
      normal and regenerating gastric mucosa as well as the intestinal mucosa of the
      rat. In the normal rat pylorus, a few alpha-beta T cells but no gamma-delta T
      cells were found in the epithelium and lamina propria. In regenerating gastric
      mucosa, all subsets of LPLs increased in number to a degree comparable to those
      in intestinal mucosa, whereas every IEL subset, though slightly increased, was
      much smaller in number than in the intestinal mucosa, consequently giving lower
      percentages of IELs. Electron microscopic observations revealed that all IELs in
      regenerating gastric mucosa were agranular, while 55% of intestinal IELs were
      large granular lymphocytes positively stained for an NK-cell, alpha-beta-cell or
      gamma-delta T-cell marker. The present results indicate that, unlike the
      intestinal epithelium, the gastric epithelium does not induce the preferential
      localization of T cells/NK cells and T-cell differentiation into granular
      lymphocytes in the epithelium even under conditions of prominent LPL
      infiltration.

PMID- 10885453
TI  - Time-related changes of developing enamel crystals after exposure to the tissue
      fluid in vivo: analysis of a subcutaneously implanted rat incisor.
AB  - To investigate the effects of tissue fluid on the growth of enamel crystals,
      upper and lower incisors extracted from 3-week-old Wistar rats were removed of
      the enamel organ, implanted subcutaneously in the dorsal portion of animals from
      the same litter, and harvested at 72 h or 1 week after implantation. The grafts
      were chemically fixed with surrounding tissues and prepared for light and
      electron microscopy, X-ray microanalysis, or for the immunohistochemistry of
      amelogenin. Mineralization of implanted enamel layers was examined by contact X
      ray microradiography. The immunoreactivities for 25 kD amelogenin in immature
      enamel decreased sequentially, starting from the surface to the deeper layers; by
      1 week after implantation, no positive reactivities remained in the entire enamel
      layers at the stages of matrix formation and early maturation. In accordance with
      the loss of enamel proteins, immature enamel gained mineral density until it
      attained higher radio opacity than that of the adjacent dentin by 1 week. In
      contrast, the radio opacity of the full thickness of the enamel at early
      maturation remained low except for a superficial thin layer. Electron microscopy
      revealed no sign of growth of original enamel crystals, but showed heavy
      precipitation of electron-dense fine granules of calcium phosphate in all layers
      of the secretory enamel and the superficial layer of enamel at early maturation,
      which showed high radio opacity. The Ca/P ratio and electron diffraction patterns
      of the granular materials precipitated between intrinsic enamel crystals
      indicated the property of hydroxy apatite or octacalcium phosphate though a
      characteristic ribbon-like profile of enamel crystals was lacking. These data
      indicate that the enamel organ blocks exogenous mineral precipitates in growing
      enamel during the stage of matrix formation and plays an essential regulatory
      role for fine enamel crystallites to grow into large hexagonal crystals.

PMID- 10885454
TI  - Villiform processes in the pharynx of the soft-shelled turtle, Trionyx sinensis
      japonicus, functioning as a respiratory and presumably salt uptaking organ in the
      water.
AB  - Some species of soft-shelled turtle have been known to use a conspicuous mass of
      villiform processes of the pharyngeal mucosa as an aquatic respiratory organ when
      staying underwater for prolonged periods, such as hibernation. Using hibernating
      turtles, Trionyx sinensis japonicus, the present study employed scanning electron
      microscopy to demonstrate for the first time the detailed morphology and
      distribution of these villiform processes. Two types of processes, complex and
      simple, could be identified. Light microscope observation of the transverse
      sections of the villi demonstrated a rich vascularization in the connective
      tissue of the villi, comprising arterioles and venules running in the core and
      capillaries in the periphery. Most of the capillaries were invaginated into the
      multilayered cuboidal epithelium. Near the tip of the villi they became swollen,
      forming sinusoidal capillaries. Transmission electron microscopy clarified the
      fine structure of the blood-water barrier, which consisted of a non-fenestrated
      endothelium and an attenuated epithelium that sandwiched a connective tissue with
      a discontinuous subendothelial and a continuous subepithelial basement lamina.
      The epithelium consisted of secretory cells, mitochondria-rich cells, and basal
      cells. The mitochondria-rich cells contained a cytoplasmic area filled with
      tubulovesicular elements. Based on their ultrastructural resemblance with the
      chloride cells in the fish and tadpole, these cells are suggested to be involved
      in the uptake of Na+ and Cl from fresh water for keeping ionic balance in the
      blood.

PMID- 10885455
TI  - The vascular supply of the villiform processes in the pharynx of the soft-shelled
      turtle, Trionyx sinensis japonicus. A scanning electron microscopic study of
      corrosion casts.
AB  - Following our observations of the fine structure of the pharyngeal villiform
      processes of the hibernating soft-shelled turtle, Trionyx sinensis japonicus
      (Yokosuka et al., 2000), this paper deals with a scanning electron microscope
      study of the resin casts of blood vessels supplying those processes. Each
      villiform process contained arterioles and venules which ran in the axial portion
      of the process; capillaries formed a network at the periphery of the connective
      tissue core of the villus. In the distal portions of the villus, the capillaries
      increased markedly in their caliber to form sinusoidal capillaries. Such a
      vascular architecture supports the view that the villiform processes serve in the
      aquatic respiration of the soft-shelled turtle. The casts indicated an occurrence
      of sphincters in the vascular bed of the villi.

PMID- 10885456
TI  - Oxovanadium(IV) and oxovanadium(V) complexes relevant to biological systems.
AB  - Different aspects of the coordination chemistry of oxovanadium(IV) and
      oxovanadium(V), relevant to the bioinorganic chemistry of vanadium, are
      presented. Some of the investigated complexes are good models for different
      aspects of the metabolism and detoxification of vanadium or for a better
      characterization and understanding of the structural and electronic peculiarities
      of the coordination spheres of VO2+ and VO2+ in biomolecules. Their structural,
      spectroscopic and magnetic properties are briefly discussed. The investigated
      systems include ligands such as reduced and oxidized glutathione, L-ascorbic
      acid, nucleotides and related systems, carbohydrates, phosphates, carboxylic
      acids, oxine derivatives and some others.

PMID- 10885457
TI  - Hydroxamido vanadates: aqueous chemistry and function in protein tyrosine
      phosphatases and cell cultures.
AB  - The protein tyrosine phosphatases (PTPases) are a group of regulatory enzymes
      that are critically important to a wide variety of cellular functions. A number
      of these PTPases have significant potential as targets for therapeutic
      intervention, for instance, in diabetes and autoimmune disease treatment. The
      hydroxylamine complex, bis(N,N-dimethylhydroxamido)hydroxooxovanadate (DMHAV), is
      an excellent inhibitor of the two PTPases, protein tyrosine phosphatase 1B
      (PTP1B) and leucocyte common antigen related phosphatase (LAR). However, because
      of the similarity of the active site architecture within the group of known
      PTPases, DMHAV is probably an effective inhibitor of most PTPases. Information
      gleaned from studies of the mechanism of inhibition of PTPases by peptide-derived
      inhibitors, together with information from comparative protein modelling and
      studies of the aqueous chemistry of DMHAV, has provided insights for the
      development of selective PTPase inhibitors. In cell cultures, DMHAV is effective
      in increasing phosphotyrosine levels on the insulin receptor and greatly
      facilitates glucose transport and glycogen synthesis. Selective PTPase inhibitors
      that are developed from the basis of the hydroxylamine motif may lead to
      effective vanadate-based complexes that have potential as therapeutic agents.

PMID- 10885458
TI  - Investigations of Amavadin.
AB  - The development of the understanding of the co-ordination chemistry and the
      properties of Amavadin, the chemical form in which vanadium is accumulated by the
      Amanita genus of mushrooms, is reviewed.

PMID- 10885459
TI  - Insulin-like effects of vanadium: basic and clinical implications.
AB  - Most mammalian cells contain vanadium at a concentration of about 20 nM, the bulk
      of which is probably in the reduced vanadyl (+4) form. Although this trace
      element is essential and should be present in the diet in minute quantities, no
      known physiological role for vanadium has been found thus far. In the late 1970s
      the vanadate ion was shown to act as an efficient inhibitor of Na+,K+-ATPase as
      well as of other related phosphohydrolases. In 1980 vanadium was reported to
      mimic the metabolic effects of insulin in rat adipocytes. During the last decade,
      vanadium has been found to act in an insulin-like manner in all three main target
      tissues of the hormone, namely skeletal muscles, adipose, and liver. Subsequent
      studies revealed that the action of vanadium salts is mediated through insulin
      receptor independent alternative pathway(s). The investigation of the
      antidiabetic potency of vanadium soon ensued. Vanadium therapy was shown to
      normalize blood glucose levels in STZ-rats and to cure many hyperglycemia-related
      deficiencies. Therapeutic effects of vanadium were then demonstrated in type II
      diabetic rodents, which do not respond to exogenously administered insulin.
      Finally, clinical studies indicated encouraging beneficial effects. A major
      obstacle, however, is overcoming vanadium toxicity. Recently, several organically
      chelated vanadium compounds were found more potent and less toxic than vanadium
      salts in vivo. Such a newly discovered organic chelator of vanadium is described
      in this review.

PMID- 10885460
TI  - Redox reactions via vanadium-induced electron transfer.
AB  - One-electron reduction and oxidation induced by vanadium complexes are
      demonstrated to be useful in oxidative and reductive transformations of carbonyl
      compounds. The redox interaction between vanadium complexes and redox-active
      ligands is achieved with coenzyme PQQ and polyanilines that afford the
      corresponding redox systems.

PMID- 10885461
TI  - Oxovanadium(IV) complexes with aromatic aldehydes.
AB  - The synthesis, structure and spectroscopic properties of complexes with the
      formula [V(IV)O(dsal)2(H2O)], where Hdsal = salicylaldehyde, o-vanillin and 3
      ethoxysalicylaldehyde, are presented. The crystal and molecular structures of
      [V(IV)O(o-van)2(H2O)] (1) (o-Hvan = o-vanillin = 3-methoxysalicylaldehyde) is
      studied by single-crystal X-ray diffraction. Each molecule exhibits an octahedral
      geometry with the two o-van ligands coordinated cis to the V(IV)O2+ group. 1 is
      the first example of a structurally characterized vanadium complex involving
      O(aldehyde) as the donor atom and this enables a comparison between the bonding
      characteristics and the contributions of O(aldehyde), O(amide), O(carboxylate)
      and O(ketone) (in acetylacetone) to the parallel hyperfine coupling constant in
      VOL2 complexes.

PMID- 10885462
TI  - Models for the active site of vanadium-dependent haloperoxidases: insight into
      the solution structure of peroxo vanadium compounds.
AB  - A combined use of electrospray ionization-mass spectrometry (ESI-MS), 51V NMR
      spectroscopy and ab initio calculations has been proved to be a powerful tool for
      obtaining direct information of the structure and the chemistry of peroxo
      vanadates in solutions. The analysis of acid solutions containing monoperoxo
      vanadates showed the occurrence of exchange reactions between solvent molecules
      in the coordination sphere of the metal. On the other hand, bisperoxo vanadates
      appear to be less prone to coordinate more than one water or alcohol molecule.
      The bisperoxo complex [VO5]- in the presence of histidine and histidine-like
      ligands, at near neutral conditions, has been studied. Coordination of one and
      two molecules of ligand is observed affording [VO5L]- and [VO5L2]-, respectively.
      Characterization of these species has been obtained by MSn experiments, which
      allowed us to distinguish specific fragmentations of the peroxidic moiety.

PMID- 10885463
TI  - Speciation in vanadium bioinorganic systems. 6. Speciation study of aqueous
      peroxovanadates, including complexes with imidazole.
AB  - Using a combination of potentiometry (glass electrode) and quantitative 51V NMR
      spectroscopy, the full speciation in the vanadate-peroxide and vanadate-peroxide
      imidazole systems was determined in the pH range 1-10 (0.150 M Na(Cl) medium, 25
      degrees C). Using the computer program LAKE, the pKa value of imidazole and the
      formation constants for 10 peroxovanadate species and also for three more species
      where a single imidazole moiety is also bound, have been calculated. The
      experimental data show a good fit to the calculated speciation model, even for
      the less abundant species. The species are either monomeric or dimeric in
      vanadium, and four resonances of the dimeric species have been unambiguously
      assigned via 2D 51V NMR. Diperoxovanadates are the favoured species at pH 2-10,
      when sufficient peroxide is present. Imidazole is found to bind strongly to them
      at pH 6-9. The equilibrium conditions are illustrated in distribution diagrams.

PMID- 10885464
TI  - Stereospecific formation of alpha-hydroxycarboxylato oxo peroxo complexes of
      vanadium(V). Crystal structure of (NBu4)2[V2O2(O2)2(L-lact)2] x 2H2O and
      (NBu4)2[V2O2(O2)2(D-lact)(L-lact)] x 2H2O.
AB  - An overview of structurally characterized alpha-hydroxycarboxylatodioxo- and
      alpha-hydroxycarboxylatooxoperoxovanadates(V) is presented and the geometric
      parameters of the V2O2 bridging core are discussed. The first case of a
      stereospecific formation of oxoperoxovanadates(V) is reported: The crystal
      structures of the isomeric compounds (NBu4)2[V2O2(O2)2(L-lact)2] x 2H2O and
      (NBu4)2[V2O2(O2)2(D-lact)(L-lact)] x 2H2O (lact = C3H4O3(2-), the anion of the
      lactic acid) differ mainly in the arrangement of the V2O2 core and in mutual
      orientation of the V=O bonds. The complexes with achiral ligands adopt the same
      structural type as the complexes formed from a racemic mixture of a chiral
      ligand, while the structure obtained using an enantiopure L,L-hydroxycarboxylate
      is different.

PMID- 10885465
TI  - Speciation of insulin-mimetic VO(IV)-containing drugs in blood serum.
AB  - The biospeciations of three potential insulin-mimetic VO(IV) compounds,
      VO(maltolate)2, VO(picolinate)2 and VO(6-Me-picolinate)2, in blood serum were
      assessed via modelling calculations, using the stability constants reported in
      the literature for the binary insulin-mimetic complexes and their ternary
      complexes formed with the most important low molecular mass binders in the serum:
      oxalic acid, lactic acid, citric acid and phosphate. The binding capabilities of
      two high molecular mass serum proteins, albumin and transferrin, were also taken
      into account.

PMID- 10885466
TI  - Synthesis and aqueous solution properties of multinuclear oxo-bridged
      vanadium(IV/V) complexes.
AB  - Reaction of the multifunctional phenolic ligands 2,5-bis[N,N
      bis(carboxymethyl)aminomethyl]hydroquinone (H6cahq), 2,2'-bis[N,N
      bis(carboxymethyl)aminomethyl]-4,4'-isopropylidenediphen ol(H6capd),2,2',2''
      tris[N,N-bis(carboxymethyl)aminomethyl]-1,1 ,1-tris(4-hydroxyphenyl)ethane
      (H9catp) and the monofunctional 2-[N,N-bis(carboxymethyl)aminomethyl]-4
      carboxyphenol (H3cacp), with VOSO4 and NaVO3 affords the oxo-bridged mixed
      valence vanadium(IV/V) Na6[(VO)4(mu-O)2(mu-cahq)2] x Na2SO4 x 20H2O (1), HnNa(3
      n)[(VO)2(mu-O)(mu-cacp)2] (2), HnNa(3-n)[(VO)4(mu-O)2(mu-capd)2] (3), HnNa(9
      n)[(VO)6(mu-O)3(mu3-catp)2] (4). In addition to the synthesis, we report the
      infrared, magnetic, optical and electrochemical properties of these complexes.
      The hydrolytic stability at different pH values was also investigated using
      visible spectroscopy.

PMID- 10885467
TI  - Biocatalytic and biomimetic oxidations with vanadium.
AB  - Approaches to the rational design of vanadium-based semi-synthetic enzymes and
      biomimetic models as catalysts for enantioselective oxidations are reviewed.
      Incorporation of vanadate ion into the active site of phytase (E.C. 3.1.3.8),
      which in vivo mediates the hydrolysis of phosphate esters, afforded a semi
      synthetic peroxidase. It catalyzed the enantioselective oxidation of prochiral
      sulfides with H2O2 affording the S-sulfoxide, e.g. in 66% ee at quantitative
      conversion of thioanisole. Under the reaction conditions the semi-synthetic
      vanadium peroxidase was stable for more than 3 days with only a slight decrease
      in turnover frequency. Amongst the transition-metal oxoanions that are known to
      be potent inhibitors of phosphatases, only vanadate resulted in a semi-synthetic
      peroxidase when incorporated into phytase. In a biomimetic approach, vanadium
      complexes of chiral Schiff base complexes were encapsulated in the super cages of
      a hydrophobic zeolite Y. Unfortunately, these ship-in-a-bottle complexes afforded
      only racemic sulfoxide in the catalytic oxidation of thioanisole with H2O2.

PMID- 10885468
TI  - Oxidation reactions catalyzed by vanadium chloroperoxidase from Curvularia
      inaequalis.
AB  - Vanadium haloperoxidases have been reported to mediate the oxidation of halides
      to hypohalous acid and the sulfoxidation of organic sulfides to the corresponding
      sulfoxides in the presence of hydrogen peroxide. However, traditional heme
      peroxidase substrates were reported not to be oxidized by vanadium
      haloperoxidases. Surprisingly, we have now found that the recombinant vanadium
      chloroperoxidase from the fungus Curvularia inaequalis catalyzes the oxidation of
      2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), a classical
      chromogenic heme peroxidase substrate. The enzyme mediates the oxidation of ABTS
      in the presence of hydrogen peroxide with a turnover frequency of 11 s(-1) at its
      pH optimum of 4.0. The Km of the recombinant enzyme for ABTS was observed to be
      approximately 35 microM at this pH value. In addition, the bleaching of an
      industrial sulfonated azo dye, Chicago Sky Blue 6B, catalyzed by the recombinant
      vanadium chloroperoxidase in the presence of hydrogen peroxide is reported.

PMID- 10885469
TI  - An orally active antidiabetic vanadyl complex, bis(1-oxy-2
      pyridinethiolato)oxovanadium(IV), with VO(S2O2) coordination mode; in vitro and
      in vivo evaluations in rats.
AB  - According to Pearson's HSAB (hard and soft acids and bases) rule, the vanadyl ion
      is classified as a hard acid. However, vanadyl-cysteine methyl ester and
      dithiocarbamate complexes with VO(S2N2) and VO(S4) coordination modes,
      respectively, that contain bonds with a combination of hard acid (VO2+) and soft
      base (sulfur) have been found to form stable complexes and exhibit insulin
      mimetic activities in in vitro and in vivo evaluations. Based on such
      observations, a purple bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) (VO(OPT))
      complex with VO(S2O2) coordination mode was prepared and found to have a strong
      insulin-mimetic activity in in vitro evaluation, which followed in vivo
      effectiveness on intraperitoneal injection and oral administration. Then, we
      examined the real-time ESR analysis of vanadyl species in the blood of live rats
      given VO(OPT) by use of the blood circulation monitoring-ESR method. The
      clearance of vanadyl species from the blood in terms of half-life (t(1/2)) was
      determined as 15 min in VO(OPT)-treated rats, while t(1/2) of VOSO4-treated rats
      was 5 min, indicating the long-term acting character of VO(OPT). On the basis of
      the results, VO(OPT) with VO(S2O2) coordination mode is proposed to be a potent
      orally active insulin-mimetic complex in treating insulin-dependent diabetes
      mellitus in experimental animals.

PMID- 10885470
TI  - Vanadyl(IV) binding to mammalian ferritins. An EPR study aided by site-directed
      mutagenesis.
AB  - During its metabolism, vanadium is known to become associated with the iron
      storage protein, ferritin. To elucidate probable vanadium binding sites on the
      protein, VO2+ binding to mammalian ferritins was studied using site-directed
      mutagenesis and EPR spectroscopy. VO2+-apoferritin EPR spectra of human H-chain
      (100% H), L-chain (100% L), horse spleen (84% L, 16% H) and sheep spleen (45% L,
      55% H) ferritins revealed the presence of alpha and beta VO2+ species in all the
      proteins, implying that the ligands for these species are conserved between the H
      and L-chains. The alpha species is less stable than the beta species and
      decreases with increasing pH, demonstrating that the two species are not pH
      related, a result contrary to earlier proposals. EPR spectra of site-directed
      HuHF variants of several residues conserved in H- and L-chain ferritins (Asp-131,
      Glu-134, His-118 and His-128) suggest that His-118 near the outer opening of the
      three-fold channel is probably a ligand for VO2+ and is responsible for the beta
      signals in the EPR spectrum. The data indicate that VO2+ does not bind to the Asp
      131 and Glu-134 residues within the three-fold channels nor does it bind at the
      ferroxidase site residues Glu-62 or His-65 or at the putative nucleation site
      residues Glu-61,64,67. While the ferroxidase site is not a site for VO2+ binding,
      mutation of residues Glu-62 and His-65 of this site to Ala affects VO2+ binding
      at His-118, located some 17 A away. Thus, VO2+ spin probe studies provide a
      window on structural changes in ferritin not seen in most previous work and
      indicate that long-range effects caused by point mutations must be carefully
      considered when drawing conclusions from mutagenesis studies of the protein.

PMID- 10885471
TI  - Water and bromide in the active center of vanadate-dependent haloperoxidases.
AB  - Two aqua-oxovanadium complexes, viz. [A-VO(H2O)(sal-L-Leu)] (1) and [VO(H2O)2(5
      Br-sal-Gly)] x H2O(2 x H2O), containing the water ligands in cis- and trans
      positions to the oxo group at V-OH2 distances ranging from 2.008 to 2.228 A, have
      been structurally characterized in order to model the apical electron density
      feature found in the structures of fungal and algal vanadate-dependent
      peroxidases. Br K-edge XAS of bromide-treated bromoperoxidase from Ascophyllum
      nodosum and model compounds (including 2 x H2O) has been used to show that the
      substrate bromide does not bind to active site vanadium but to a light atom,
      possibly carbon, in its vicinity.

PMID- 10885473
TI  - Vanadium nitrogenase.
AB  - The topic, vanadium nitrogenase, is reviewed with respect to biological
      characteristics and findings on its structure and functions. Structural models
      (vanadium complexes containing ligands related to the active center in the iron
      vanadium cofactor) and functional models for the reductive protonation of
      dinitrogen, the activation of alkynes and reductive C-C coupling of isocyanides
      are addressed.

PMID- 10885472
TI  - Chemistry and insulin-like properties of vanadium(IV) and vanadium(V) compounds.
AB  - The chemistry of vanadium compounds that can be taken orally is very timely since
      a vanadium(IV) compound, KP-102, is currently in clinical trials in humans, and
      the fact that human studies with inorganic salts have recently been reported.
      VO(acac)2 and VO(Et-acac)2 (where acac is acetylacetonato and Et-acac is 3-ethyl
      2,4-pentanedionato) have long-term in vivo insulin mimetic effects in
      streptozotocin induced diabetic Wistar rats. Structural characterization of
      VO(acac)2 and two derivatives, VO(Me-acac)2 and VO(Et-acac)2, in the solid state
      and solution have begun to delineate the size limits of the insulin-like active
      species. Oral ammonium dipicolinatooxovanadium(V) is a clinically useful
      hypoglycemic agent in cats with naturally occurring diabetes mellitus. This
      compound is particularly interesting since it represents the first time that a
      well-characterized organic vanadium compound with the vanadium in oxidation state
      five has been found to be an orally effective hypoglycemic agent in animals.

PMID- 10885474
TI  - Density-functional study of vanadate-glycylserine isomers.
AB  - Optimized geometries (BP86/I) and computed 51V NMR chemical shifts (GIAO-B3LYP/I)
      are reported for selected [VO(OH)(OH2)(glyser')] isomers and deprotonated forms
      thereof (glyser' = H2N-CH2-CO-N-CH(CH2OH)-COO). The serine moiety can coordinate
      either with its carboxylic or with its alcoholic function, in accord with
      experiment. As found previously for the parent complex with glycylglycine, the
      water molecule is not bound to vanadium in the deprotonated, anionic forms.
      Qualitative agreement with experimental trends in delta(51V) is obtained for the
      anionic, but not for the neutral complexes.

PMID- 10885475
TI  - Vanadate oligomer interactions with myosin.
AB  - 'Monovanadate' containing a mixture of at least four different vanadate species
      and 'decavanadate' containing apparently only two vanadate species, mainly
      decameric species, inhibit myosin and actomyosin ATPase activities. The addition
      of myosin to 'monovanadate' and 'decavanadate' solutions promotes differential
      increases on the 51V NMR spectral linewidths of vanadate oligomers. The relative
      order of line broadening upon myosin addition, reflecting the interaction of the
      vanadate oligomers with the protein, was V10 > V4 > V1 = 1, whereas no changes
      were observed for monomeric vanadate species. It is concluded that decameric and
      tetrameric vanadate species interact quite potently with the protein and affect
      myosin as well actomyosin ATPase activities.

PMID- 10885476
TI  - Vanadate oligomer inhibition of passive and active Ca2+ translocation by the Ca2+
      pump of sarcoplasmic reticulum.
AB  - 'Monovanadate' containing mainly monomeric, dimeric and tetrameric vanadate
      species or 'decavanadate', containing mainly decameric vanadate species inhibits
      the passive and the active efflux of Ca2+ through the sarcoplasmic reticulum
      calcium pump. When the efflux of Ca2+ by sarcoplasmic reticulum vesicles is not
      associated with ATP synthesis both vanadate solutions inhibit the passive efflux
      of Ca2+. However, only 'decavanadate' exerts noticeable effects when the efflux
      of Ca2+ is associated with ATP synthesis being the active efflux of Ca2+ almost
      completely inhibited by decameric species concentration as low as 40 microM.

PMID- 10885477
TI  - Speciation in the vanadate-alanylhistidine-peroxide system.
AB  - The speciation in the quaternary aqueous H+-H2VO4(-)-H2O2-L-alpha-alanyl-L
      histidine (Ah) system has been determined from quantitative 51V NMR measurements
      and potentiometric data (glass electrode). The study was performed in 0.150 M
      Na(Cl) medium at 25 degrees C. Data were evaluated with the computer program
      LAKE, which is able to treat combined potentiometric and NMR data. In the ternary
      H+-H2VO4(-)-Ah system, two complexes, (H+)p(H2VO4-)q(Ah)r, having (p, q, r)
      values (0, 1, 1) and (1, 1, 1) (pKa = 6.88) explain all data. In the quaternary
      H+-H2VO4(-)-H2O2-Ah system, seven complexes were determined in addition to all
      binary and ternary complexes, four with a V/X/Ah ratio 1:1:1 and three with a
      ratio 1:2:1 (X = peroxo ligand). VX2Ah2- and VX2Ah- (pKa = 8.26) are the main
      quaternary complexes and predominate in the pH range 5 to 9. Chemical shifts,
      compositions and formation constants for all the quaternary complexes are given,
      and equilibrium conditions are illustrated in distribution diagrams.

PMID- 10885478
TI  - The vanadium isotopic constitution of petroleum asphaltenes: La Luna Formation
      (Venezuela).
AB  - High-resolution mass spectrometry indicates that the isotopic abundance of 50V of
      the Late Cretaceous La Luna petroleum asphaltenes of marine origin (highly
      enriched with V > 2000 ppm) is higher by about 3.5% than that of the inorganic
      source (VOSO4 x 5H2O, Merck). We propose that the difference in the 50V/51V
      values between the La Luna petroleum asphaltenes and the inorganic source can be
      best ascribed to the biological processing of seawater vanadium. The fact that
      the V isotopic compositions of petroleum asphaltenes vary over a very narrow
      range (2.46-2.52) suggests essentially the same (or similar) and fixed biological
      source of vanadium.

PMID- 10885479
TI  - A (17)O NMR study of peroxide binding to the active centre of bromoperoxidase
      from Ascophyllum nodosum.
AB  - The (17)O NMR of bromoperoxidase in Tris buffer at pH 8 treated with (17)O
      enriched H2O2 reveals direct binding of peroxide to active site vanadium both in
      the symmetric and asymmetric modes, the latter possibly due to hydroperoxide. In
      addition, non-active site HVO2(O2)2(2-) is detected. The results are counter
      checked with NMR data on peroxovanadium model compounds.

PMID- 10885480
TI  - Oxo-vanadium as a spin probe for the investigation of the metal coordination
      environment of imidazole glycerol phosphate dehydratase.
AB  - Imidazole glycerol phosphate dehydratase (IGPD) catalyses the dehydration of
      imidazole glycerol phosphate to imidazole acetol phosphate, an important late
      step in the biosynthesis of histidine. IGPD, isolated as a low molecular weight
      and inactive apo-form, assembles with specific divalent metal cations to form a
      catalytically active high molecular weight metalloenzyme. Oxo-vanadium ions also
      assemble the protein into, apparently, the same high molecular weight form but,
      uniquely, yield a protein without catalytic activity. The VO2+ derivative of IGPD
      has been investigated by electron paramagnetic resonance (EPR), electron nuclear
      double resonance (ENDOR) and electron spin echo envelope modulation (ESEEM)
      spectroscopy. The spin Hamiltonian parameters indicate the presence of multiple
      14N nuclei in the inner coordination sphere of VO2+ which is corroborated by
      ENDOR and ESEEM spectra showing resonances attributable to interactions with 14N
      nuclei. The isotropic superhyperfine coupling component of about 7 MHz determined
      by ENDOR is consistent with a nitrogen of coordinated histidine imidazole(s). The
      ESEEM Fourier-transform spectra further support the notion that the VO2+
      substituted enzyme contains inner-sphere nitrogen ligands. The isotropic and
      anisotropic 14N superhyperfine coupling components are similar to those reported
      for other equatorially coordinated enzymatic histidine imidazole systems. ESEEM
      resonances from axial 14N ligands are discussed.

PMID- 10885481
TI  - Synthesis, characterization and bioactivity of a new VO2+/aspirin complex.
AB  - A new VO2+ complex with salicylic acid acetate (Aspirin) of formula
      C18H18Cl2O12V2 was synthesized and characterized. Its biological effects upon
      cell proliferation, differentiation and promotion of tyrosine protein
      phosphorylation have been tested in two lines of osteoblast-like cells in
      culture.

PMID- 10885482
TI  - Insulin mimesis of vanadium derivatives. Oxidation of cysteine by V(V) oxo
      diperoxo complexes.
AB  - Kinetics of the oxidation of cysteine to cystine by four V(V) oxo diperoxo
      complexes [VO(O2)2L] possessing insulin mimetic activity, where L = oxalate(oxa),
      picolinate (pic), bipyridil (bipy), phenanthroline(phen), were performed in water
      at 10 degrees C by the UV or stopped-flow technique. 51V NMR spectra indicate
      that oxa undergoes a total ligand dissociation differently from pic, bipy and
      phen which hold their ligands also in solution. The observed reactivity is deeply
      affected by the identity of the ligand. The process seems to require coordination
      of the cysteine to the metal, followed by oxidation within the coordination
      sphere. In this respect phen and bipy make the coordination of cysteine much
      easier than oxa and pic. It is suggested, also on the basis of some preliminary
      observations concerning the oxidation of C6H5CH2SH, that the oxidation process is
      triggered by an electron transfer step. The rate of this step would be higher for
      oxa and pic than for phen and bipy. The observation that the oxidative ability of
      these vanadium peroxo complexes is dependent upon the nature of the ligands might
      match the analogous finding that their insulin mimetic activity is also modulated
      by the ligand identities.

PMID- 10885483
TI  - Structural study of the interaction of vanadate with the ligand 1,2-dimethyl-3
      hydroxy-4-pyridinone (Hdmpp) in aqueous solution.
AB  - The interaction of vanadate with the ligand 1,2-dimethyl-3-hydroxy-4-pyridinone
      (Hdmpp) was studied in aqueous solution using a combination of multinuclear NMR
      and EPR spectroscopies, as well as potentiometry and cyclic voltammetry. The
      different species in solution were identified and characterized, and their pKa
      values and stability constants determined. The vanadium complexes formed in
      solution are strongly dependent on media composition (ionic strength, presence of
      buffer), pH and metal-to-ligand ratio (M:L). Two major species--V(V)/dmpp and
      V(V)/(dmpp)2--are formed in a 140 mM NaCl solution within the pH range 4.5 to
      9.0, when M:L = 1:2. In the presence of excess ligand (M:L < or = 1:5), only the
      1:2 complex is present, and at pH < 4 paramagnetic species are detected by EPR in
      solution, thus indicating a reducing capacity of the ligand. Cyclic voltammetry
      shows that redox processes in solution are not just electron transfer, but are
      accompanied by chemical reactions. The pK, values and stability constants were
      determined both by 51V NMR spectroscopy and potentiometry. The present results
      have a particular interest in the understanding of the aqueous solution chemistry
      in aerobic conditions of bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)
      oxovanadium(IV) complex, VO(dmpp)2, a vanadium compound with potential insulin
      mimetic properties.

PMID- 10885484
TI  - N-Salicylidenehydrazides as versatile tridentate ligands for dioxovanadium(V)
      complexes.
AB  - The Schiff base ligand derived from salicylaldehyde and benzoic acid hydrazide
      (H2salhyph) reacts with potassium metavanadate in methanol solution to yield the
      potassium salt of the corresponding cis-dioxovanadium(V) complex K[VO2(salhyph)]
      (1). 1 crystallizes with one molecule of methanol in the monoclinic space group
      P2(1)/c with a = 1332.3(7), b = 669.9(2), c = 1809.0(8) pm, beta = 100.96(4)
      degrees, and Z = 4. The reactions of 1 with several proton acidic compounds
      including water, methanol, ethane-1,2-diol (H2ed), and proton acids lead to
      neutral monooxovanadium(V) and cis-dioxovanadium(V) complexes ([VO2(Hsalhyph)]
      (2); [V2O3(salhyph)2] (3); [VO(OMe)(salhyph)(HOMe)] (4); [VO(Hed)(salhyph)] (5)).
      The crystal structure of 2 (triclinic space group P1 with a = 677.79(5), b =
      842.89(7), c = 1214.66(9) pm, alpha = 79.931(1), beta = 75.466(1), gamma =
      73.391(1) degrees, and Z = 2) reveals that the protonation of the cis
      dioxovanadium(V) complex 1 occurs at the hydrazide nitrogen atom of the ligand
      system. This was confirmed by the spectroscopic properties of the deuterium
      derivative.

PMID- 10885485
TI  - Towards models of vanadate-dependent haloperoxidases: the hydroxyl side chain.
AB  - Monomeric VO2+ and dimeric VO3+ complexes containing salicylidene
      aminocarboxylates predominantly with hydroxyl side chains (L-serine, L
      homoserine, L-threonine, L-tyrosine) have been characterized.

PMID- 10885486
TI  - Vanadium catalyzed reduction of dioxygen to hydrogen peroxide: an oscillating
      process.
AB  - In acid isopropanol/water solution and aerobic conditions, (Bu)4N+VO3- in the
      presence of an initial amount of H2O2, catalyzes the autoxidation of isopropanol
      to acetone and the contextual dioxygen reduction to hydrogen peroxide, which
      accumulates in solution. We have observed that, in the system under examination,
      the build-up of H2O2 concentration shows an oscillatory behavior. Speciation of
      the peroxovanadium complexes in iPrOH/H2O has been explored with the combined use
      of 51V NMR, UV-Vis and ESI-MS techniques.

PMID- 10885487
TI  - Plasma concentrations of blood coagulation factor VII measured by immunochemical
      and amidolytic methods.
AB  - Ever since the coagulant activity of blood coagulation factor VII (FVII:C) was
      identified as a risk indicator of cardiac death, a large number of studies have
      measured FVII protein concentrations in plasma. FVII protein concentrations are
      either measured immunologically with an ELISA method (FVII:Ag) or estimated with
      an amidolytic method (FVII:Am). We have investigated whether FVII:Am is a
      valuable alternative to FVII:Ag. FVII:Ag and FVII:Am were measured in 147 plasma
      samples from blood donors, patients on oral anticoagulant therapy, postmenopausal
      women on hormone replacement therapy, in postprandial plasma, in cold activated
      plasma and in FVII deficient plasma. There was a positive correlation (r=0.96)
      between FVII:Ag and FVII:Am with slightly but significantly higher values for
      FVII:Ag (FVII:Ag= 106 U/ml and FVII:Am=100 U/ml; p <0.001). A significant
      correlation (r=0.93) was still observed after omitting the data from patients on
      oral anticoagulant therapy, with mean values of 113 U/ml for FVII:Ag and 110 U/ml
      for FVII:Am (p < 0.01). In a linear regression analysis, the intercept (alpha=
      21.50) was different from zero (p < 0.0001) and the slope (beta=1.16) was
      different from 1.0 (p < 0.001). Only a few points (3.1%) in a difference plot
      were present outside the expected 95% interval calculated from the analytical
      imprecision of the two methods. Therefore, we consider the amidolytic method an
      acceptable alternative to the ELISA method when analysing citrated plasma samples
      containing only enzymatically functional FVII protein, but the results cannot be
      directly transferred from one method to the other.

PMID- 10885488
TI  - Severe retinopathy in type 1 diabetic patients is not related to the level of
      plasma homocysteine.
AB  - The vascular-injuring amino acid homocysteine was previously shown to be
      increased in plasma in type 1 diabetic patients with clinical signs of
      nephropathy. Previous studies have also shown an inconsistent relationship
      between the development of diabetic nephropathy and retinopathy, indicating
      different pathogenetic mechanisms. In this study, plasma homocysteine was
      measured in 25 type 1 diabetic patients with a well-characterized form of severe
      retinopathy. Furthermore, a group of 24 type 1 diabetic patients with similar age
      at onset of diabetes and diabetes duration with no or minimal background
      retinopathy were investigated, in order to determine whether plasma homocysteine
      levels are different from those in patients with severe retinopathy. Patients
      with severe retinopathy did not have higher plasma levels of homocysteine (13.9
      micromol/L; 5.9-30.7, median and range) than those without retinopathy (10.4
      micromol/L; 5.7-18.9). Within the group of patients with severe retinopathy,
      increased homocysteine levels were confined to the patients (19.9 micromol/L;
      10.0-30.7, n=9) with serum creatinine levels > 100 micromol/L, compared to those
      patients (9.6; 5.9-14.3 micromol/L, n=15) with a serum creatinine below 100
      micromol/L. None of the patients without or with minimal background retinopathy
      had serum creatinine levels > 100 micromol/L. We conclude that diabetic
      retinopathy is not associated with increased plasma homocysteine levels, but
      plasma homocysteine accumulates, probably owing to reduced glomerular filtration,
      in diabetic patients with signs of nephropathy. In these patients, the promoting
      effect of nephropathy on the development of retinopathy does not seem to be
      mediated through homocysteine.

PMID- 10885489
TI  - High insulin and low IGF-I plasma levels following pancreas transplantation in
      rats. Implications for bone and mineral metabolism.
AB  - Primary disturbances in mineral metabolism and deficiencies in insulin and
      insulin-like growth factor-I (IGF-I) have been implicated in the pathogenesis of
      diabetic osteopenia. This prompted us to investigate whether normal bone minerals
      and bone morphology are preserved after pancreas transplantation. To this end, 8
      inbred rats (transplants) were compared with 9 sham-operated rats (controls) 20
      months after orthotopic pancreas transplantation. While basal levels of insulin
      remained unaffected by transplantation, an oral glucose load elicited
      hyperinsulinemia (integrated incremental response: mean +/- SEM, 62+/-8 nmol l(
      1) 60 min in transplants vs. 32+/-6 nmol l(-1) 60 min in controls; p<0.01) in the
      presence of normal glucose levels. Fecal and urinary excretion and fractional
      intestinal absorption of calcium, magnesium and phosphorus, net calcium
      absorption and the respective serum mineral levels were unchanged after
      transplantation, as were those of the calciotropic hormones. Serum osteocalcin
      and bone alkaline phosphatase remained unaffected, and urinary excretion of
      pyridinium and deoxypyridinium were unchanged. Fasting plasma IGF-I concentration
      was significantly decreased in transplants (930+/-42 ng ml(-1)) vs. control rats
      (1074+/-49 ng ml(-1); p < 0.05). Despite similar physical and chemical properties
      of bone in both groups, histomorphometry revealed slight osteopenia in transplant
      rats, as reflected by a 38% reduction in the cancellous bone area of the proximal
      tibial metaphysis. Plasma IGF-I levels were significantly correlated with bone
      mineral apposition rate (r=0.70, p<0.02), osteoblast perimeter (r=0.60, p<0.05)
      and osteoid perimeter (r=0.60, p<0.05). In conclusion, pancreas transplantation
      preserves physical and chemical properties of bone, but bone metabolism is not
      completely normal after transplantation, as evidenced by decreased cancellous
      bone. This might have resulted from the insulin resistance associated with the
      lowering of the plasma IGF-I level, which was correlated with the mineral
      apposition rate.

PMID- 10885490
TI  - Decreased plasma cholesterol esterification and cholesteryl ester transfer in
      hypopituitary patients on glucocorticoid replacement therapy.
AB  - Cardiovascular risk is increased in hypopituitary patients. No data are available
      with respect to the effect of glucocorticoid replacement therapy on high density
      lipoproteins (HDL) metabolism in such patients. Plasma lecithin:cholesterol acyl
      transferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid
      transfer protein (PLTP) are important determinants of HDL remodelling. The
      possible influence of conventional glucocorticoid replacement on plasma lipids,
      plasma LCAT, CETP and PLTP activity levels, as well as on plasma cholesterol
      esterification (EST) and cholesteryl ester transfer (CET) was evaluated in 24
      consecutive hypopituitary patients (12 men and 12 women) with untreated growth
      hormone deficiency of whom 17 had adrenal insufficiency and were treated with
      cortisone acetate, 25 to 37.5 mg daily. Twenty-three patients were on stable
      levothyroxin therapy and 22 patients used sex steroids. Urinary excretion of
      cortisol and cortisone metabolites was higher (p<0.001) in glucocorticoid-treated
      patients. Body mass index (p<0.08) and fat mass (p<0.12) were not significantly
      different in patients receiving and not receiving glucocorticoids. Fasting blood
      glucose, plasma insulin and insulin resistance were similar in the groups. Plasma
      total (p<0.05) and very low+low density lipoprotein cholesterol (p<0.01) were
      lower in patients receiving glucocorticoids, whereas HDL cholesterol and plasma
      triglycerides were not different between patients treated and not treated with
      glucocorticoids. Plasma LCAT activity was 45% lower (p<0.02) and CETP activity
      was 34% lower (p<0.05) in patients on glucocorticoid treatment. Multiple
      regression analysis showed that these effects were independent of gender and fat
      mass. In glucocorticoid-receiving patients, plasma EST and CET were decreased by
      80% (p<0.01) and by 58% (p<0.05), respectively. These changes were at least
      partly attributable to lower LCAT and CETP activity levels. In contrast, plasma
      PLTP activity was not different between patients with and without glucocorticoid
      treatment, suggesting that exogenous glucocorticoids exert a different regulatory
      effect on plasma CETP compared to PLTP. In conclusion, this preliminary study
      suggests that conventional glucocorticoid replacement in hypopituitary patients
      is associated with a decrease in plasma cholesterol esterification and
      cholesteryl ester transfer, indicating that these steps in HDL metabolism are
      impaired. Such abnormalities in HDL metabolism could be involved in increased
      cardiovascular risk in glucocorticoid-treated hypopituitary patients, despite a
      lack of deterioration in plasma lipids.

PMID- 10885491
TI  - Evaluation of plasma retinol-binding protein as a surrogate measure for plasma
      retinol concentrations.
AB  - Plasma retinol-binding protein (RBP) concentrations have been suggested as
      surrogate indicators for plasma retinol concentrations in the assessment of
      vitamin A status in less technologically developed settings. Plasma RBP was
      measured by radial immunodiffusion and plasma retinol by high performance liquid
      chromatography in a cross-sectional study of 900 pregnant women at the Queen
      Elizabeth Central Hospital, Blantyre, Malawi. The Spearman correlation
      coefficient between plasma RBP and retinol concentrations was 0.95 (p<0.0001). By
      linear regression, 0.70 micromol l(-1) retinol was equivalent to 21.1 mg l(-1)
      RBP. With these cut-off points for defining vitamin A deficiency, there was high
      concordance between categorical descriptions of deficiency using retinol and RBP
      by chi-square analysis (p<0.001). Measurement of plasma RBP by radial
      immunodiffusion is simple, inexpensive, and does not require expensive
      instrumentation. Plasma RBP concentrations measured by radial immunodiffusion are
      highly correlated with plasma retinol and can be used as a simple surrogate
      measure for vitamin A concentrations in large field studies.

PMID- 10885492
TI  - Validation of an endogenous reference technique for the calibration of
      microdialysis catheters.
AB  - In order to validate the use of urea as an internal reference for the calibration
      of microdialysis catheters, both subcutaneous and muscle measurements were taken
      in 11 healthy volunteers. The equilibration calibration of urea, glucose and
      lactate, and the internal reference (3H-glycerol retrodialysis) calibration of
      glycerol were performed in both the muscle and fat. These data were then compared
      with those taken from the arterial plasma. Based on the average arterial
      interstitial fluid concentration difference, the urea microdialysis relative
      recovery was estimated from dialysate and plasma content of urea. Interstitial
      urea was then used as an endogenous reference for the calculation of the relative
      recovery of each substance. This was carried out after defining the relative
      recovery ratios (RR) that were obtained from in vitro measurements on crystalline
      solutions with the assumption that RR in vivo = RR in vitro. The data demonstrate
      that the interstitial fluid concentrations of glucose, lactate and glycerol can
      be calculated from the knowledge of plasma and microdialysate content of urea
      together with the RR in vitro. Also, the data that were obtained using urea as an
      endogenous reference showed a significant correlation with those that were
      achieved using either equilibration or internal reference (retrodialysis)
      techniques for calibrating the microdialysis devices.

PMID- 10885493
TI  - High-frequency oscillatory ventilation does not decrease endothelin release in
      lung-lavaged rabbits.
AB  - High-frequency oscillatory ventilation (HFO) has been shown to reduce lung injury
      and pulmonary arterial pressure (PAP). We hypothesized that HFO leads to
      decreased endothelin 1 (ET-1) and endothelin 3 (ET-3) release when compared to
      conventional mechanical ventilation (CMV) in lung-lavaged rabbits. DESIGN:
      Prospective, randomized, controlled animal study. In 26 adult New Zealand White
      Rabbits ventilated by CMV or HFO under hypoxemic and normoxemic conditions after
      lung lavage (CMV-hypo: n = 5; CMV-normo: n = 8; HFO-hypo: n = 7; HFO-normo: n =
      6) we recorded systemic and PAP, measured blood gases, ET-1 and ET-3 and
      calculated intrapulmonary venous admixture during a 4-h experiment. ET-1 was
      significantly increased after lavage (p < 0.05) with no further increase until
      the end of the experiment. Neither pulmonary arterial nor systemic arterial ET-1
      differed between CMV and HFO or between hypoxemia and normoxemia. Systemic
      arterial ET-3, however, was significantly higher in HFO-hypo than in the other
      two groups ventilated under normoxemic conditions at the end of the experiment
      (HFO-hypo vs. CMV-normo, p < 0.05; HFO-hypo vs. HFO-normo, p < 0.05). PAP showed
      a continuous increase in all groups (p < 0.05). We did not find any correlation
      between PAP and ET-1 or ET-3. Intrapulmonary venous admixture increased in
      animals ventilated under hypoxemic conditions, whereas it decreased after lung
      lavage in those ventilated under normoxemic conditions until the end of the
      experiment (HFO-normo, p < 0.05). CONCLUSIONS: This study suggests that HFO does
      not decrease ET-1 and ET-3 release compared to CMV in lung-lavaged rabbits.
      Hypoxemia, however, may increase ET-3 release from the lungs, leading to an
      increased intrapulmonary shunt.

PMID- 10885494
TI  - Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism
      associated with mutations in the human Ca2+-sensing receptor gene in three Danish
      families.
AB  - We screened three unrelated Danish families with familial hypocalciuric
      hypercalcemia (FHH) for mutations in the Ca2+-sensing receptor (CASR) gene by
      polymerase chain reaction amplification and DNA sequencing of exons 2-7, which
      include the entire coding region of the gene. In one family the affected
      individuals have a T-->C mutation that changes the normal arginine at codon 220
      to a tryptophan. In the other two FHH families, affected individuals have the
      same A-->G mutation, leading to conversion of the normal glycine at codon 552 to
      an arginine. These results confirm that FHH can be caused by non-conservative
      missense mutations in the CASR gene leading to abnormal calcium homeostasis. Both
      mutations are located in the amino-terminal extracellular domain of the receptor,
      which contains the binding site for extracellular Ca2+, the CASR's principal
      physiological agonist.

PMID- 10885495
TI  - Lack of association between 27-bp repeat polymorphism in intron 4 of the
      endothelial nitric oxide synthase gene and the risk of coronary artery disease.
AB  - The gene encoding endothelial nitric oxide synthase (ecNOS) is a candidate gene
      for the mediation of initial endothelial cell damage seen in arteriosclerosis.
      Although the association of ecNOS polymorphisms with hypertension has been
      studied extensively, there is little information regarding its association with
      coronary artery disease (CAD). We decided to study a 27 base-pair tandem repeat
      polymorphism in intron 4 of the ecNOS gene in 1043 individuals (413 controls, 630
      patients with CAD) who consecutively underwent coronary angiography at our
      institution. The frequencies of the genotypes drawn from 1038 individuals were
      0.69, 0.28 and 0.03 in the controls and 0.73, 0.25 and 0.02 in individulas with
      CAD for the ecNOS4b/b, ecNOS4b/a and ecNOS4a/a genotypes, respectively (p = n.s).
      There was no shift of the genotype frequencies from the expected distribution
      based on the Hardy-Weinberg equilibrium. Neither the rare ecNOS4a allele nor the
      ecNOS4a/a genotype conferred an independent risk factor for CAD in subgroups,
      e.g. smokers, diabetic individuals, hypertensive individuals and individuals with
      a low conventional risk for CAD. In five individuals we identified an additional
      27-bp repeat in the ecNOS gene (ecNOS4c), which occurred heterozygous with the
      ecNOS4b allele (ecNOS4b/c genotype). In conclusion, the ecNOS4a allele as well as
      the ecNOS4a/a genotype did not show a general association with CAD in the studied
      European population. Even in high-risk subgroups the ecNOS4a/4a genotype did not
      represent an independent risk factor for CAD. In addition, the severity of CAD
      was not associated with the ecNOS4a allele/ecNOS4a/a genotype.

PMID- 10885496
TI  - Removal of IgG from normal plasma and plasma from untreated patients with active
      Crohn's disease--effect on levels of contact factors.
AB  - Protein G columns were used to remove IgG from human plasma, and the effect on
      levels of factor XII, factor XI and prekallikrein was studied in functional
      tests. IgG was detected in PAGE immunoblot experiments with Fc-specific
      antibodies. Removal of the bulk of IgG in a procedure based on a low plasma
      dilution (1+2.5) allowed the passage of an IgG fraction along with the contact
      factors. This fraction was found to be present in higher amounts in plasma from
      patients with Crohn's disease (n=5) than in control plasma (n=12). In a previous
      study, PAGE immunoblot experiments showed that part of the prekallikrein was
      removed along with IgG when a higher plasma dilution (1+10.8) was used (Scand J
      Clin Lab Invest 1999; 59: 55-64). This observation was supported by results in
      the present work based on parallel assays with the peptide substrates S-2302 and
      Bz-Pro-Phe-Arg-pNA. The prekallikrein fraction removed was present in a
      functional state differing from the main part of prekallikrein by yielding
      kallikrein with a significantly increased activity against the substrate S-2366.
      This prekallikrein fraction was present in higher amounts in patient plasma than
      in control plasma. Part of the corresponding amidase activity was blocked by lima
      bean trypsin inhibitor, suggesting its presence in association with factor XI.
      The results also indicated that prekallikrein activator activity was connected
      with this fraction. With the high dilution procedure an extensive removal of IgG
      from the patient plasma was obtained compared to the control plasma.

PMID- 10885497
TI  - H107, a new aminoglycoside anti-Pseudomonas antibiotic produced by a new strain
      of Spirillospora.
AB  - Spirillospora spp. (strain 719) has been the source of several antibiotics. One
      of these designated H107 is produced as a trace. Compared with other antibiotics
      produced by the same strain, it was obtained only from the broth filtrate after
      precipitation with acetic acid followed by extraction with n-butanol. It was a
      water soluble metabolite active against Gram-negative bacteria and especially
      Pseudomonas spp., and was identified as an aminoglycoside compound. This is the
      first report of aminoglycoside anti-Pseudomonas production by Spirillospora.

PMID- 10885498
TI  - Effect of suprainhibitory concentrations of quinolones on hydrophobicity and
      motility of Serratia marcescens.
AB  - The effect of suprainhibitory concentrations of quinolones (ciprofloxacin,
      enoxacin and norfloxacin) on the growth, hydrophobicity and motility of a
      nosocomial pathogen Serratia marcescens was studied. A postantibiotic effect
      (PAE) was induced by 2x of 4x MIC concentrations for 0.5 h. By using the 2x MIC
      concentrations all three quinolones induced equally long PAE approximately 1 h.
      The longest PAE of 5.4 h at 4x MIC concentration was induced by enoxacin. The
      results obtained showed that suprainhibitory concentrations of quinolones
      significantly stimulated the adhesion of S. marcescens to xylene, with the
      exception of enoxacin, which inhibited the adhesion to 61.2% at 4x MIC
      concentration. These results correlated with those in the salt aggregation test.
      The adhesion of strains to nitrocellulose filters did not influence the
      aftereffect of suprainhibitory concentrations of quinolones. Exposure of
      bacterial cells to suprainhibitory concentrations of ciprofloxacin and
      norfloxacin caused a reduction in motility, while this effect was more distinct
      at 4x MIC concentration. The results suggest that any consideration of
      postantibiotic effects should include the residual antibiotic effects on
      virulence factors, in addition to the defined suppression of bacterial regrowth.

PMID- 10885499
TI  - Ability of casamino acids to support gellan production by Sphingomonas
      paucimobilis ATCC 31461.
AB  - The ability of casamino acids and vitamin-assay casamino acids to support gellan
      production by Sphingomonas paucimobilis ATCC 31461 was examined in a medium
      containing glucose or corn syrup as the carbon source relative to yeast extract
      supplementation. When glucose or corn syrup served as the carbon source, the
      presence of yeast extract in the growth medium stimulated gellan production by
      strain ATCC 31461 on casamino acids. Using vitamin-assay casamino acids as the
      nitrogen source, the addition of vitamins lowered gellan synthesis by glucose
      grown cells regardless of yeast extract supplementation while gellan elaboration
      by corn syrup-grown strain ATCC 31461 cells could only be increased by
      supplementing vitamins into medium lacking yeast extract. Independent of carbon
      source, the absence of yeast extract in the medium reduced biomass production.
      Biomass production by the strain grown on either carbon source was increased by
      supplementing vitamins in the medium containing yeast extract.

PMID- 10885500
TI  - Isolation and characterization of transposon-induced chlorate resistant mutants
      of the cyanobacterium Anabaena species PCC 7120.
AB  - Mutants of Anabaena sp. PCC 7120 resistant to chlorate were isolated using
      transposon mutagenesis. The Anabaena population of 5 x 10(7) cells ml(-1) and log
      phase Escherichia coli cultures in undisturbed conditions produced maximum
      exconjugants. Nitrate-promoted growth and cellular constituents observed in the
      parent were absent in the mutants. Nitrate repressed heterocyst formation and N2
      fixation in the parent, but had little or no effect on the mutants.

PMID- 10885501
TI  - The status of the cagA gene does not predict Helicobacter pylori-associated
      peptic ulcer disease in Singapore.
AB  - Discrepancies among reports from different geographical regions worldwide on the
      association between the presence of cagA and peptic ulcer disease prompted this
      study on the predictive value of the cagA gene in Helicobacter pylori-associated
      gastroduodenal diseases in the Singapore population. H. pylori strains were
      obtained from 169 patients with a peptic ulcer, 83 with non-ulcer dyspepsia, and
      nine with gastric cancer. The presence of the cagA gene was evaluated by
      polymerase chain reaction (PCR). The expected 400 bp PCR product coding for the
      cagA gene was present in 232/261 (89%) H. pylori isolates. Of these, 151/169
      (89%) strains from patients with peptic ulcer, 73/83 (88%) strains from patients
      with non-ulcer dyspepsia and 8/9 (89%) strains from cancer patients were positive
      for the cagA gene. There was no statistically significant difference between the
      prevalence of cagA-positive strains from patients with distinct clinical outcomes
      (p > 0.05). The prevalence of cagA-positive strains in the Singapore population
      is high regardless of clinical disease status. The results suggest that the cagA
      gene is not a universal virulence marker of H. pylori.

PMID- 10885502
TI  - Evaluation of methods for the microbiological control of natural corks for
      sparkling wine bottles.
AB  - The various parameters proposed in Norm 0.20/95 of Catalunya (Spain) for the
      microbiological analysis of natural corks for sparkling wines were evaluated. The
      best results were obtained through the use of 1/4 Ringer's solution or saline for
      rinsing with an agitation time of 30 min, and an agitation speed of 150-200 rpm.
      Tryptone soya agar (TSA) and Sabouraud dextrose agar (SDA) were used as a culture
      medium for the bacteria and fungi, respectively, and a cultivation time of 48 h
      and incubation temperatures of 37 +/- 2 degrees C for bacteria and 28 degrees C
      for yeast and filamentous fungi.

PMID- 10885503
TI  - Effect of pH and inorganic carbon concentration on growth, glycerol production,
      photosynthesis and dark respiration of Dunaliella salina.
AB  - The growth of Dunaliella salina was studied with respect to pH and varying
      concentrations of NaHCO3 in the medium. The growth rate, photosynthesis and dark
      respiration were maximal at pH 8 and 4 mM NaHCO3 in the medium. Photosystem I of
      the Hill reaction was affected more by inorganic carbon concentration than
      photosystem II.

PMID- 10885504
TI  - Adhesion of blood platelets to collagen and fibrinogen after treatment with
      cisplatin and its complex with glutathione.
AB  - Cisplatin (cis-diamminedichloroplatinum II, CDDP) is one of the most widely used
      chemotherapy drugs. Unfortunately, it induces serious side effects such as
      haematological toxicity. The aim of the present study was to evaluate the effect
      of CDDP on the first step in blood platelet activation-platelet adhesion, induced
      by thrombin or adenosine diphosphate (ADP), to collagen and fibrinogen. The
      action of cisplatin was compared with the action of cisplatin glutathione complex
      (GS-Pt) on platelet adhesion and on free radical generation measured by
      chemiluminescence. Pretreatment of blood platelets with cisplatin (0.1-20 microM)
      caused a dose- and time-dependent reduction of platelet adhesion to collagen and
      fibrinogen (p <0.05). The GS-Pt complex (20 microM, 30 min) had a stronger
      inhibitory effect on this process. Moreover, the complex (R2 = 0.992; p <0.05)
      also stimulated the chemiluminescence of blood platelets to a greater extent than
      CDDP alone (R2 = 0.999; p <0.01). The results suggest that inhibition of platelet
      adhesion in the presence of cisplatin and its complex with glutathione correlates
      with the generation of reactive oxygen species in these cells.

PMID- 10885505
TI  - Male reproductive toxicity of vincristine: ultrastructural changes in the
      epididymal epithelial apical cell.
AB  - The toxic effect of vincristine on the apical cells of the rat caput epididymis
      was investigated. The drug was administered at 20 and 40 microg/kg body weight
      daily for 15 days. Light microscopy using semithin sections, and transmission
      electron microscopy, of the caput epididymis were undertaken. The results
      revealed that the basal region of the apical cell was in contact with the
      basement membrane and the luminal end took part in endocytosis. The apical cells
      reflected a dose-dependent response to vincristine (VCR) treatment. In general
      the changes included protrusion of the apical ends deep into the lumen, with the
      nucleus of the cell located in such protruded ends, and an increase in the
      abundance of lysosomal bodies and multivesicular bodies. These changes reflected
      the physiological response of the apical cell to VCR treatment rather than toxic
      manifestations.

PMID- 10885506
TI  - Effects of luteolin on arylamine N-acetyltransferase activity in human liver
      tumour cells.
AB  - The human liver tumour cell line (J5) was selected in order to evaluate whether
      or not luteolin affected arylamine N-acetyltransferase (NAT) activity. Using high
      performance liquid chromatography, the NAT activity for acetylation of arylamine
      substrates (2-aminofluorene and p-aminobenzoic acid) was determined. The
      cytosolic NAT activity in human liver tumour cells was 2.74+/-0.26 and 1.68+/
      0.20 nmol/min/mg of protein for 2-aminofluorene and p-aminobenzoic acid,
      respectively. Luteolin displayed a dose-dependent inhibition to cytosolic NAT
      activity and intact human liver tumour cells. Time-course experiments showed that
      NAT activity measured from intact human liver tumour cells was inhibited by
      luteolin for up to 24 h. Using standard steady-state kinetic analysis, it was
      shown that luteolin was a possible noncompetitive inhibitor to NAT activity in
      cytosols. This report is the first to show how luteolin affects NAT activity in
      human liver tumour cells.

PMID- 10885507
TI  - DNA degradation in the kidney of folic acid-treated guinea pigs.
AB  - Previous investigators agree on the increased DNA synthesis and destruction of
      tissues caused by folic acid (FA) administered parenterally. This study aims to
      clarify whether DNA degradation due to the destruction of cells and nuclei
      precedes DNA synthesis following FA administration. Forty guinea pigs were
      divided into four groups: group 1, contained 10 controls; in group 2, ten animals
      received intraperitoneally 300 mg/kg of body wt FA; in group 3, ten animals
      received FA and 12 h later frusemide intramuscularly in a dose of 7 mg/kg body
      wt; and finally in group 4, ten animals received frusemide as in group 3. FA
      produced necrosis of the epithelial cells of the convoluted tubules as the
      detection of the beta-aminoisobutyric acid end product of DNA and thymine
      catabolism indicated. Frusemide administered in group 3 had a favourable effect
      on the acute renal failure induced by FA.

PMID- 10885508
TI  - Bioassays of APONIN-3 and -4 with rabbit erythrocytes.
AB  - Rabbit erythrocytes in methanolic phosphate medium were used to bioassay the
      activity of authentic samples of methyl stearate and methyl palmitate (in 10%
      methanol:90% water, v/v), which had been identified as apparent oceanic naturally
      occurring cytolins (APONIN-3 and -4) produced by Nannochloris oculata. The two
      natural products are notable for cytolytic activity toward the unarmoured
      dinoflagellate, Gymnodinium breve Davis, an organism responsible for red tides
      consisting of harmful algal blooms in the Gulf of Mexico and along the eastern
      coast of the United States. Bioassays were done with heparinized rabbit blood.
      The absorbance at 540 nm was observed for 15 min in comparison with a sample
      treated with haemolysing agent. The results indicated that at reasonable
      concentrations of 1-10 ppm, neither was a haemolysin, although such
      concentrations caused cytolysis of G. breve cultures.

PMID- 10885509
TI  - Pericentric inversion in human chromosome 8 and spherocytosis.
AB  - A cytogenetic study of a patient revealed a pericentric inversion in chromosome
      8, and spherocytes in 10% of cells, in a routine blood smear. The critical
      portion which affected the expression of spherocytosis appeared to be localized
      at 8p22-8q21. The mother's karyotyping showed the transmission of the inversion
      to the child.

PMID- 10885510
TI  - Macrofilaricidal activity of tetracycline against the filarial nematode
      Onchocerca ochengi: elimination of Wolbachia precedes worm death and suggests a
      dependent relationship.
AB  - Filarial nematodes are important and widespread parasites of animals and humans.
      We have been using the African bovine parasite Onchocerca ochengi as a
      chemotherapeutic model for O. volvulus, the causal organism of 'river blindness'
      in humans, for which there is no safe and effective drug lethal to adult worms.
      Here we report that the antibiotic, oxytetracycline is macrofilaricidal against
      O. ochengi. In a controlled trial in Cameroon, all adult worms (as well as
      microfilariae) were killed, and O. ochengi intradermal nodules resolved, by nine
      months' post-treatment in cattle treated intermittently for six months. Adult
      worms removed from concurrent controls remained fully viable and reproductively
      active. By serial electron-microscopic examination, the macrofilaricidal effects
      were related to the elimination of intracellular micro-organisms, initially
      abundant. Analysis of a fragment of the 16S rRNA gene from the O. ochengi micro
      organisms confirmed them to be Wolbachia organisms of the order Rickettsiales,
      and showed that the sequence differed in only one nucleotide in 858 from the
      homologous sequence of the Wolbachia organisms of O. volvulus. These data are, to
      our knowledge, the first to show that antibiotic therapy can be lethal to adult
      filariae. They suggest that tetracycline therapy is likely to be macrofilaricidal
      against O. volvulus infections in humans and, since similar Wolbachia organisms
      occur in a number of other filarial nematodes, against those infections too. In
      that the elimination of Wolbachia preceded the resolution of the filarial
      infections, they suggest that in O. ochengi at least, the Wolbachia organisms
      play an essential role in the biology and metabolism of the filarial worm.

PMID- 10885511
TI  - The evolution of the serotonergic nervous system.
AB  - The pattern of development of the serotonergic nervous system is described from
      the larvae of ctenophores, platyhelminths, nemerteans, entoprocts, ectoprocts
      (bryozoans), molluscs, polychaetes, brachiopods, phoronids, echinoderms,
      enteropneusts and lampreys. The larval brain (apical ganglion) of spiralian
      protostomes (except nermerteans) generally has three serotonergic neurons and the
      lateral pair always innervates the ciliary band of the prototroch. In contrast,
      brachiopods, phoronids, echinoderms and enteropneusts have numerous serotonergic
      neurons in the apical ganglion from which the ciliary band is innervated. This
      pattern of development is much like the pattern seen in lamprey embryos and
      larvae, which leads the author to conclude that the serotonergic raphe system
      found in vertebrates originated in the larval brain of deuterostome
      invertebrates. Further, the neural tube of chordates appears to be derived, at
      least in part, from the ciliary band of deuterostome invertebrate larvae. The
      evidence shows no sign of a shift in the dorsal ventral orientation within the
      line leading to the chordates.

PMID- 10885512
TI  - Penguins use the two-voice system to recognize each other.
AB  - The sound-producing structure in birds is the syrinx, which is usually a two-part
      organ located at the junction of the bronchi. As each branch of the syrinx
      produces sound independently, many birds have two acoustic sources. Thirty years
      ago, we had anatomical, physiological and acoustical evidence of this two-voice
      phenomenon but no function was known. In songbirds, often these two voices with
      their respective harmonics are not activated simultaneously but they are obvious
      in large penguins and generate a beat pattern which varies between individuals.
      The emperor penguin breeds during the Antarctic winter, incubating and carrying
      its egg on its feet. Without the topographical cue of a nest, birds identify each
      other only by vocal means when switching duties during incubation or chick
      rearing. To test whether the two-voice system contains the identity code, we
      played back the modified call of their mate to both adults and also the modified
      call of their parents to chicks. Both the adults and the chicks replied to
      controls (two voices) but not to modified signals (one voice being experimentally
      suppressed). Our experiments demonstrate that the beat generated by the
      interaction of these two fundamental frequencies conveys information about
      individual identity and also propagates well through obstacles, being robust to
      sound degradation through the medium of bodies in a penguin colony. The two-voice
      structure is also clear in the call of other birds such as the king penguin,
      another non-nesting species, but not in the 14 other nesting penguins. We
      concluded that the two-voice phenomenon functions as an individual recognition
      system in species using few if any landmarks to meet. In penguins, this coding
      process, increasing the call complexity and resisting sound degradation, has
      evolved in parallel with the loss of territoriality.

PMID- 10885513
TI  - Oestrogen regulates male aggression in the non-breeding season.
AB  - Extensive research has focused on territorial aggression during the breeding
      season and the roles of circulating testosterone (T) and its conversion to 17beta
      oestradiol (E2) in the brain. However, many species also defend territories in
      the non-breeding season, when circulating T-levels are low. The endocrine control
      of non-breeding territoriality is poorly understood. The male song sparrow of
      Washington State is highly territorial year-round, but plasma T is basal in the
      non-breeding season (autumn and winter). Castration has no effect on aggression
      in autumn, suggesting that autumnal territoriality is independent of gonadal
      hormones. However, non-gonadal sex steroids may regulate winter territoriality
      (e.g. oestrogen synthesis by brain aromatase). In this field experiment, we
      treated wild non-breeding male song sparrows with a specific aromatase inhibitor
      (fadrozole, FAD) using micro-osmotic pumps. FAD greatly reduced several
      aggressive behaviours. The effects of FAD were reversed by E2 replacement.
      Treatment did not affect body condition or plasma corticosterone, suggesting that
      all subjects were healthy These data indicate that E2 regulates male aggression
      in the non-breeding season and challenge the common belief that aggression in the
      non-breeding season is independent of sex steroids. More generally, these results
      raise fundamental questions about how sexual and/or aggressive behaviours are
      maintained in a variety of model vertebrate species despite low circulating
      levels of sex steroids or despite castration. Such non-classical endocrine
      mechanisms may be common among vertebrates and play an important role in the
      regulation of behaviour.

PMID- 10885514
TI  - The role of male accessory gland protein Acp36DE in sperm competition in
      Drosophila melanogaster.
AB  - A crucial factor determining sperm fertilization success in multiply mated
      Drosophila melanogaster females is the efficiency with which sperm are stored.
      This process is modulated by the accessory gland protein Acp36DE. In this study,
      we show that the effect of Acp36DE on sperm storage itself alters the outcome of
      sperm competition. As second-mating males, Acp36DE1 (null) males had
      significantly lower P2-values than Acp36DE2 (truncation) or Acp36DE+ (control)
      males, as might be expected as the null males' sperm are poorly stored. We used
      spermless males, which are null for Acp36DE, to show that, in the absence of
      sperm co-transfer, Acp36DE itself could not displace first-male sperm. The
      results therefore suggest that males null for Acp36DE suffer in sperm
      displacement because fewer sperm are stored or retained, not because Acp36DE
      itself displaces sperm. Acp36DE1 (null) males also gained significantly fewer
      fertilizations than controls when they were the first males to mate. Using
      spermless males, we also showed that significantly more second-male offspring
      were produced following the transfer of Acp36DE by spermless first-mating males.
      This implies that the transfer of Acp36DE itself by the first male facilitated
      the storage or use of the second male's sperm and that co-transfer with sperm is
      not necessary for Acp36DE effects on second-male sperm storage. Acp36DE may
      persist in the reproductive tract and aid the storage of any sperm including
      those of later-mating males or prime the female for future efficient sperm
      storage. Our results indicate that mutations in genes that affect sperm storage
      can drastically affect the outcome of sperm competition.

PMID- 10885515
TI  - Sperm precedence in a novel context: mating in a sessile marine invertebrate with
      dispersing sperm.
AB  - The compound ascidian Diplosoma listerianum releases aquatic sperm which are
      dispersed passively to potential mates as individual gametes prior to storage of
      sperm, internal fertilization and brooding of embryos. The storage of exogenous
      sperm enables D. listerianum to produce a lengthy series of progeny following a
      brief period of mating. Molecular paternity analysis following sequential mating
      of colonies in laboratory culture revealed a consistent pattern with a clear
      initial bias in paternity towards the first of two acting males. The sites of
      sperm storage and fertilization and the morphology of the ovary in D. listerianum
      suggest that this bias reflects first-in-first-out use of individual stored
      gametes. The proportion of second-male paternity subsequently increased with time
      within the progeny arrays. This may have reflected the ageing or passive loss of
      first-male sperm. It is also possible that the modular nature of the organism
      contributed to this temporal trend: any recently budded colony modules maturing
      in the interval between matings would have been available exclusively to second
      male sperm as virgin zooids. Two sets of mating trials were run. In the first,
      the collection of progeny suffered an interruption of 13 days and each male
      gained a larger proportion of recorded paternity within the progeny analysed when
      mating first rather than when mating second. In one mating combination, the first
      male obtained almost 100% of recorded paternity. In the second set of trials,
      with different clonal combinations, the complete sequence of progeny was
      collected and the estimated overall proportion of second-male paternity (P2) was
      consistently > 0.5. Taken as a whole, the results suggest that the overall P2
      value can vary widely within the population studied. Proposed mechanisms of
      mating-order effects in species with copulatory mating include several which can
      have no counterpart in indirect aquatic mating since they involve the active
      removal, sealing off, volumetric displacement or incapacitation of first-male
      ejaculates. It is nevertheless clear that mating-order effects can be pronounced
      during the type of non-copulatory mating examined here, which is widespread in
      marine invertebrates.

PMID- 10885516
TI  - A trade-off between reproduction and a condition-dependent sexually selected
      ornament in the house sparrow Passer domesticus.
AB  - Reproductive effort was manipulated in a free-living population of house sparrows
      (Passer domesticus) to investigate the trade-off between reproductive investment
      and the expression of a condition-dependent sexually selected ornament.
      Phenotypic plasticity in the expression of this trait was related to the
      experimentally manipulated size of the brood reared by a male. Males that
      invested more in current reproduction subsequently became more attractive to
      females in this population as they showed a preference for males with smaller
      badges. This supports the argument that direct benefits are a primary focus for
      mate choice by females. Trade-offs between reproductive effort and the expression
      of sexual ornaments are a potentially important source of phenotypic variation in
      both sexual ornaments and life-history traits.

PMID- 10885517
TI  - Experimental analyses of sexual and natural selection on short tails in a
      polygynous warbler.
AB  - We believe that no experimental study has yet tested Darwin's idea that, as well
      as generating trait elaboration, intersexual selection might sometimes drive sex
      biased trait reduction. Here we present the results of two experiments exploring
      the negative relationship between tail length and reproductive success in male
      golden-headed cisticolas (Cisticola exilis). In the first experiment,
      artificially shortening a male's tail produced a dramatic increase in his
      reproductive success, measured as either the number of females nesting or number
      of chicks Hedged on his territory. A second experiment, in which manipulated
      birds were flown through a maze, revealed that short tails also impose costs by
      reducing aerodynamic performance during slow-speed foraging flight. Because tail
      shortening yields reproductive benefits and viability costs, we conclude it has
      evolved via sexual selection. Disentangling exactly how short tails enhance male
      reproductive success is more difficult. Male-male competition appears partly
      responsible: aerodynamic theory predicts that tail reduction enhances high-speed
      flight and, in line with this, shortened-tail males spent more time engaged in
      high-speed aerial chases of rivals and defended higher-quality territories.
      However, shortened-tail males had higher reproductive success independent of
      territory quality and spent more time in aerial displays which may be directed at
      females. This suggests that tail shortening is also favoured via female choice
      based on male phenotype.

PMID- 10885518
TI  - Size-specific defensive structures in a horned weevil confirm a classic battle
      plan: avoid fights with larger opponents.
AB  - A rigid sheath that extends deep into the prothorax of male Parisoschoenus
      expositus serves to receive the horns of opponents in battles over females. The
      male cannot use his own horn unless he receives his opponent's horn in his
      sheath. The length of a male's sheath is always approximately equal to the length
      of his own horns, so his body design is appropriate only for horn-locking battles
      with males whose horns are equal to or shorter than his own. Horn length and
      sheath length are dimorphic with respect to each other and to an indicator of
      body size. The switch points between morphs are very nearly the same for several
      relationships, so the different aspects of fighting morphology are tightly
      coordinated.

PMID- 10885519
TI  - Regional endemism and cryptic species revealed by molecular and morphological
      analysis of a widespread species of Neotropical catfish.
AB  - The lower Central American landscape was fully emergent approximately three
      million years ago, an event which marked the beginning of the Great American
      biotic interchange. Freshwater fishes participated in the biotic interchange.
      Because primary freshwater fishes are restricted to freshwater, they provide an
      excellent system for investigating the interplay of historical and recent
      processes on the assembly, structure and diversity of the regions' aquatic
      ecosystems. We focused on examining the history of diversification for a species
      of catfish (Pimelodella chagresi) whose distribution spans multiple, isolated
      drainage basins across the Isthmian landscape and into north-western South
      America. Analysis of mitochondrial DNA haplotypes and morphological traits
      indicated that P. chagresi, as currently recognized, comprises a species complex.
      In addition, along the Pacific slope of Panama, repeated dispersion,
      diversification, extinction and possibly hybridization are thought to underlie a
      complex distribution of haplotypes. Overall, the results underscore the
      tremendous importance of historical processes on regional biodiversity.

PMID- 10885520
TI  - Hot spots, indicator taxa, complementarity and optimal networks of taiga.
AB  - If hot spots for different taxa coincide, priority-setting surveys in a region
      could be carried out more cheaply by focusing on indicator taxa. Several previous
      studies show that hot spots of different taxa rarely coincide. However, in
      tropical areas indicator taxa may be used in selecting complementary networks to
      represent biodiversity as a whole. We studied beetles (Coleoptera), Heteroptera,
      polypores or bracket fungi (Polyporaceae) and vascular plants of old growth
      boreal taiga forests. Optimal networks for Heteroptera maximized the high overall
      species richness of beetles and vascular plants, but these networks were least
      favourable options for polypores. Polypores are an important group indicating the
      conservation value of old growth taiga forests. Random selection provided a
      better option. Thus, certain groups may function as good indicators for
      maximizing the overall species richness of some taxonomic groups, but all taxa
      should be examined separately.

PMID- 10885521
TI  - Depressed pollination in habitat fragments causes low fruit set.
AB  - In central New South Wales, Australia, flowers of Acacia brachybotrya and
      Eremophila glabra plants growing in linear vegetation remnants received less
      pollen than conspecifics in nearby reserves. Pollen supplementation increased
      fruit production by both species, indicating pollen limitation of fruit set.
      Together these observations explain why fruit production by these species was
      depressed in linear-strip populations relative to nearby reserves. This study
      confirms that habitat fragmentation can lead to decline in pollination and
      subsequent fruit set in wild plant populations. Disrupted pollination
      interactions of the kind documented in this study may offer a substantial
      challenge to the conservation of biodiversity in fragmented landscapes.

PMID- 10885522
TI  - Determinants of the abundance of invasive annual weeds: community structure and
      non-equilibrium dynamics.
AB  - The dynamics of an annual pasture community are described from a five-year
      experimental and monitoring study. The community was dominated by two grasses
      (Lolium rigidum and Vulpia bromoides) and a legume (Trifolium subterraneum). Fits
      of population dynamic models to per capita rates of population change indicate
      that interactions between the grasses were generally strong, while interactions
      between the grasses and legumes were weaker. Most, but not all, of the net
      effects of competition on population growth could be attributed to interactions
      occurring during plant growth. Phase-plane analysis indicated that, for a
      constant environment, a joint equilibrium of the two grasses is unstable since
      interspecific competition between Lolium and Vulpia is stronger than
      intraspecific competition. Consequently, the community will tend to a mixture of
      only one or other of the grass species and T. subterraneum, depending on the
      founding composition of the pasture. Analysis of data taken from a year in which
      a drought occurred (1993-1994) demonstrated profound effects on all three
      species. Modelling of the long-term impacts of the effects of repeated droughts
      showed that disturbance of this form overrides the founder effect observed under
      constant conditions. Consequently, Vulpia is ultimately able to invade any
      mixture of the other species in environments where stochastic disturbances occur.

PMID- 10885523
TI  - An application of the matching law to evaluate the allocation of two- and three
      point shots by college basketball players.
AB  - We applied the matching equation to evaluate the allocation of two- and three
      point shots by male and female college basketball players from a large Division 1
      university. The matching law predicts that the proportion of shots taken from
      three-point range should match the proportional reinforcement rate produced by
      such shots. Thus, we compared the proportion of three-point shots taken relative
      to all shots to the proportion of three-point shots scored relative to all shots
      scored. However, the matching equation was adjusted to account for the greater
      reinforcer magnitude of the three-point basket (i.e., 1.5 times greater than the
      two-point basket reinforcer magnitude). For players with substantial playing
      time, results showed that the overall distribution of two- and three-point shots
      was predicted by the matching equation. Game-by-game shot distribution was
      variable, but the cumulative proportion of shots taken from three-point range as
      the season progressed was predicted almost perfectly on a player-by-player basis
      for both male and female basketball players.

PMID- 10885524
TI  - Reinforcing variability in adolescents with autism.
AB  - Five adolescents with autism, 5 adult control participants, and 4 child controls
      received rewards for varying their sequences of responses while playing a
      computer game. In preceding and following phases, rewards were provided at
      approximately the same rate but were independent of variability. The most
      important finding was that, when reinforced, variability increased significantly
      in all groups. Reinforced variability could provide the necessary behavioral
      substrate for individuals with autism to learn new responses.

PMID- 10885525
TI  - Effects of continuous and intermittent reinforcement for problem behavior during
      functional communication training.
AB  - We evaluated the effectiveness of functional communication training (FCT) in
      reducing problem behavior and in strengthening alternative behavior when FCT was
      implemented without extinction. Following the completion of functional analyses
      in which social-positive reinforcement was identified as the maintaining variable
      for 5 participants' self-injurious behavior (SIB) and aggression, the
      participants were first exposed to FCT in which both problem behavior and
      alternative behavior were reinforced continuously (i.e., on fixed-ratio [FR] 1
      schedules). During subsequent FCT conditions, the schedule of reinforcement for
      problem behavior was made more intermittent (e.g., FR 2, FR 3, FR 5, etc.),
      whereas alternative behavior was always reinforced according to an FR 1 schedule.
      Results showed that 1 participant's problem behavior decreased and alternative
      behavior increased during FCT when both behaviors were reinforced on FR 1
      schedules. The remaining 4 participants shifted response allocation from problem
      to alternative behavior as the schedule of reinforcement for problem behavior
      became more intermittent. These results suggest that individuals might acquire
      alternative responses during FCT in spite of inconsistencies in the application
      of extinction, although even small errors in reinforcement may compromise
      treatment effects.

PMID- 10885526
TI  - Skill acquisition in the implementation of functional analysis methodology.
AB  - Functional analysis methodology is a powerful assessment tool for identifying
      contingencies that maintain a wide range of behavior disorders and for developing
      effective treatment programs. Nevertheless, concerns have been raised about the
      feasibility of conducting functional analyses in typical service settings. In
      this study, we examined the issue of skill acquisition in implementing functional
      analyses by evaluating an instructional program designed to establish a basic set
      of competencies. Eleven undergraduate students enrolled in a laboratory course in
      applied behavior analysis served as participants. Their performance was assessed
      during scripted simulations in which they played the roles of "therapists" who
      conducted functional analyses and trained graduate students played the roles of
      "clients" who emitted self-injurious and destructive behaviors. To approximate
      conditions under which an individual might conduct an assessment with limited
      prior training, participants read a brief set of materials prior to conducting
      baseline sessions. A multiple baseline design was used to assess the effects of
      training, which consisted of reading additional materials, watching a videotaped
      simulation demonstrating correct procedural implementation, passing a written
      quiz, and receiving feedback on performance during sessions. Results showed that
      participants scored a relatively high percentage of correct therapist responses
      during baseline, and that all achieved an accuracy level of 95% or higher
      following training that lasted about 2 hr. These results suggest that basic
      skills for conducting functional analyses can be acquired quickly by individuals
      who have relatively little clinical experience.

PMID- 10885527
TI  - Competition between noncontingent and contingent reinforcement schedules during
      response acquisition.
AB  - We examined the extent to which noncontingent reinforcement (NCR), when used as
      treatment to reduce problem behavior, might interfere with differential
      reinforcement contingencies designed to strengthen alternative behavior. After
      conducting a functional analysis to identify the reinforcers maintaining 2
      participants' self-injurious behavior (SIB), we delivered those reinforcers under
      dense NCR schedules. We delivered the same reinforcers concurrently under
      differential-reinforcement-of-alternative-behavior (DRA) contingencies in an
      attempt to strengthen replacement behaviors (mands). Results showed that the NCR
      plus DRA intervention was associated with a decrease in SIB but little or no
      increase in appropriate mands. In a subsequent phase, when the NCR schedule was
      thinned while the DRA schedule remained unchanged, SIB remained low and mands
      increased. These results suggest that dense NCR schedules may alter establishing
      operations that result in not only suppression of problem behavior but also
      interference with the acquisition of appropriate behavior. Thus, the
      strengthening of socially appropriate behaviors as replacements for problem
      behavior during NCR interventions might best be achieved if the NCR schedule is
      first thinned.

PMID- 10885529
TI  - A comparison of procedures for programming noncontingent reinforcement schedules.
AB  - We compared two methods for programming and thinning noncontingent reinforcement
      (NCR) schedules during the treatment of self-injurious behavior (SIB). The
      participants were 3 individuals who had been diagnosed with mental retardation.
      Results of functional analyses indicated that all participants' SIB was
      maintained by positive reinforcement (i.e., access to attention or food).
      Following baseline, the effects of two NCR schedule-thinning procedures were
      compared in multielement designs. One schedule (fixed increment) was initially
      set at fixed-time 10-s reinforcer deliveries and was also thinned according to
      fixed-time intervals. The other schedule (adjusting IRT) was initially determined
      by participants' baseline interresponse times (IRTs) for SIB and was thinned
      based on IRTs observed during subsequent treatment sessions. Results indicated
      that both schedules were effective in initially reducing SIB and in maintaining
      response suppression as the schedules were thinned.

PMID- 10885528
TI  - Further analysis of idiosyncratic antecedent influences during the assessment and
      treatment of problem behavior.
AB  - Recent research findings suggest that idiosyncratic variables can influence the
      outcomes of functional analyses (E. G. Carr, Yarbrough, & Langdon, 1997). In the
      present study, we examined idiosyncratic environment-behavior relations more
      precisely after identifying stimuli (i.e., a particular toy and social
      interaction) associated with increased levels of problem behavior. Two children,
      an 8-year-old boy with moderate mental retardation and a 5-year-old boy with no
      developmental delays, participated. Results of functional analyses for both
      children indicated that idiosyncratic antecedent stimuli set the occasion for
      occurrences of problem behavior (hand biting or hand flapping) and that problem
      behavior persisted in the absence of social contingencies. Further analyses were
      conducted to identify specific components of the stimuli that occasioned problem
      behavior. Treatments based on results of the analyses successfully reduced self
      injury and hand flapping.

PMID- 10885530
TI  - A procedure to teach self-control to children with attention deficit
      hyperactivity disorder.
AB  - This study examined the use of a progressive delay procedure combined with verbal
      mediation to teach self-control to children with attention deficit disorder.
      Results showed that when participants were initially given the choice between an
      immediate smaller reinforcer and a larger delayed reinforcer, all participants
      chose the smaller reinforcer. When slight delays to obtain a larger reinforcer
      were instated in conjunction with intervening verbal activity, all participants
      demonstrated self-control regardless of the content of the verbal activity.

PMID- 10885531
TI  - Using positive peer reporting to improve the social interactions and acceptance
      of socially isolated adolescents in residential care: a systematic replication.
AB  - We studied how rewarding youth in residential care for publicly reporting
      positive social behavior influenced the social interactions and acceptance of
      their most socially isolated peers. Results showed that the intervention resulted
      in substantial improvements in social interactions by the previously isolated
      peers. Peer acceptance ratings also improved for 2 of the target youths.

PMID- 10885532
TI  - Effects of escape to alone versus escape to enriched environments on adaptive and
      aberrant behavior.
AB  - Escape-maintained aberrant behavior may be influenced by two outcomes: (a) a
      break from the activity and (b) subsequent access to preferred activities. To
      assess this hypothesis, a treatment was developed that analyzed response
      allocation across two break options: break alone and break with access to
      preferred social activities. The break with preferred activities decreased
      aberrant behavior and increased appropriate behavior.

PMID- 10885533
TI  - The effects of different adults as therapists during functional analyses.
AB  - The differential effects of caregivers and inpatient staff members as therapists
      on behavior were evaluated within a reversal design. Results indicated that
      problem behaviors were higher in the presence of caregivers relative to inpatient
      staff. These results are discussed in terms of how antecedent stimuli can affect
      functional analysis outcomes.

PMID- 10885535
TI  - The effects of response cost in the treatment of aberrant behavior maintained by
      negative reinforcement.
AB  - Positive reinforcement contingencies can sometimes be used to decrease problem
      behavior maintained by negative reinforcement (e.g., escape). In the current
      study, we evaluated the extent to which response cost (i.e., contingent removal
      of a preferred stimulus) would compete with the negative reinforcer maintaining
      destructive behavior. The response cost contingency reduced destructive behavior
      by 87% from baseline levels even though the negative reinforcement contingency
      (i.e., escape) remained in place.

PMID- 10885534
TI  - Effects of a checklist on self-assessment of blood glucose level by a memory
      impaired woman with diabetes mellitus.
AB  - This study evaluated effects of a checklist on the accuracy of self-assessment of
      blood glucose level by a diabetic woman with memory impairments caused by viral
      encephalitis. The checklist consisted of 54 steps for operating an electronic
      glucometer, which the subject performed in sequence and checked off when
      completed. Following introduction of the checklist, the percentage of steps
      completed correctly increased in simulated and actual blood glucose tests and
      yielded clinically useful information.

PMID- 10885536
TI  - Effects of high-probability requests on the latency to initiate academic tasks.
AB  - The purpose of this study was to evaluate the effectiveness of a high-probability
      request sequence on the latency to and duration of compliance to a request for
      completion of an independent math assignment. The participant was an elementary
      school student with learning disabilities who exhibited noncompliance during math
      instruction. The results showed that high-probability requests were effective in
      reducing the latency to compliance but only minimally affected duration of
      engagement.

PMID- 10885537
TI  - Reconstitution of mediatophore-supported quantal acetylcholine release.
AB  - Synaptic transmission of a nerve impulse is an extremely rapid event relying on
      transfer of brief chemical impulses from one cell to another. This transmission
      is dependent upon Ca2+ and known to be quantal, which led to the widely accepted
      vesicular hypothesis of neurotransmitter release. However, at least in the case
      of rapid synaptic transmission the hypothesis has been found difficult to
      reconcile with a number of observations. In this article, we shall review data
      from experiments dealing with reconstitution of quantal and Ca2+-dependent
      acetylcholine release in: i) proteoliposomes, ii) Xenopus oocytes, and iii)
      release-deficient cell lines. In these three experimental models, release is
      dependent on the expression of the mediatophore, a protein isolated from the
      plasma membrane of cholinergic nerve terminals of the Torpedo electric organ. We
      shall discuss the role of mediatophore in quantal acetylcholine release, its
      possible involvement in morphological changes affecting presynaptic membrane
      during the release, and its interactions with others proteins of the cholinergic
      nerve terminal.

PMID- 10885538
TI  - Intracerebroventricular infusion of CHO5, a rat monoclonal antibody directed
      against mouse low-affinity nerve growth factor receptor (p75NTR), specifically
      labels basal forebrain cholinergic neurons in mouse brain.
AB  - The finding that basal forebrain cholinergic cells are specifically endowed with
      the low-affinity nerve growth factor receptor p75NTR has been employed to develop
      a cholinergic immunotoxin in rats by covalently linking the monoclonal antibody
      192IgG against the rat p75NTR with the cytotoxic protein saporin (192IgG
      saporin). Following intracebroventricular application of 192IgG-saporin, the
      antibody conjugate is taken up into cholinergic cells via the p75NTR,
      retrogradely transported to the cell body, where saporin exerts cytotoxic action.
      The lack of an appropriate antibody directed against mouse p75NTR has been
      hampered the development of a mouse-specific cholinergic immunotoxin, which
      should be a useful tool to study effects of cortical cholinergic deficits on
      processing of amyloid precursor protein in transgenic mice with Alzheimer
      pathology. To develop an appropriate mouse-specific immunotoxin, a variety of
      antibodies directed against mouse p75NTR were tested. Using double labeling
      immunocytochemistry, the rat monoclonal antibody CHO5 against mouse p75NTR was
      found to label mouse basal forebrain neurons, which also demonstrated
      immunoreactivity for choline acetyltransferase and the high-affinity nerve growth
      factor receptor, TrkA. Intracerebroventricular infusion of CHO5 in mice resulted
      in an accumulation of the antibody in cholinergic cells within the basal
      forebrain, suggesting that CHO5 is a suitable candidate to develop a mouse
      specific cholinergic immunotoxin.

PMID- 10885539
TI  - Acetyl-CoA metabolism in cholinergic neurons and their susceptibility to
      neurotoxic inputs.
AB  - Cholinergic neurons, unlike other brain cells utilize acetyl-CoA not only for
      energy production but also for acetylcholine (ACh) synthesis. Therefore,
      suppression of acetyl-CoA metabolism by different neurotoxic inputs may be
      particularly harmful for this group of cells. Differentiation of SN56 cholinergic
      hybrid cells increased their choline acetyltransferase (ChAT) activity and ACh
      content but depressed pyruvate dehydrogenase activity and acetyl-CoA content.
      Differentiated cells were more susceptible to acute and chronic influences of
      aluminum, NO and amyloid-beta. Al decreased acetyl-CoA content, ACh release and
      increased Ca accumulation in differentiated cells (DC) to much higher degree than
      in non-differentiated ones (NC). NO strongly depressed acetyl-CoA level and
      increased ACh release in DC but did not affect NC. Additive effects of Al and NO
      were seen in DC but not in NC. Also long term suppressory effects of amyloid
      beta, Al and NO on cholinergic phenotype and morphologic maturation were more
      evident in DC than in NC. Thus, relative shortage of acetyl-CoA in highly
      differentiated cholinergic neurons could make them particularly susceptible to
      degenerative insults in the course of different cholinergic encephalopathies.

PMID- 10885541
TI  - Targeted neutralization of calcineurin, by expression of an inhibitor peptide
      under the control of a cholinergic specific promoter in PC12 cells, promotes
      neurite outgrowth in the presence of NGF.
AB  - We have characterized a region of the mouse vesicular acetylcholine
      transporter(VAChT)/choline acetyltransferase (ChAT) gene locus that serves as a
      cholinergic-specific promoter for the expression of both VAChT and ChAT genes, as
      well as a reporter gene (LacZ) in vivo. We have used this promoter to direct the
      expression of an inhibitor peptide, derived from the calcineurin (CalN)
      autoregulatory domain, to directly neutralize the function of CalN to define the
      role of this Ca2+/Calmodulin regulated phosphatase in neurite outgrowth. Targeted
      inhibition of CalN promotes neurite outgrowth in PC12 cells in the presence of
      NGF, as early as 24 h after transfection. Inhibition of CalN-mediated enhancement
      of neurite outgrowth in PC12 cells reaches a maximum effect within the first 4 to
      6 days after transfection, and does not cause adverse effects when highly
      expressed for up to 12 days. Cyclosporin A, a nontargeted CalN inhibitor,
      increases the number of neurites in mock transfected cells by 1.5 fold, while in
      transfected PC12 cells, the expression of the CalN inhibitor peptide increases
      the neurite number by 1.8 fold. These data demonstrate that CalN is an important
      regulator of the neurotrophic response in cholinergic cells and may prove
      valuable in developing treatment strategies to promote recovery from neurological
      injury.

PMID- 10885542
TI  - Evidence for forebrain cholinergic neuronal loss in congenital ornithine
      transcarbamylase deficiency.
AB  - Congenital ornithine transcarbamylase (OTC) deficiency in humans results in
      failure to thrive, hypotonia, seizures and mental retardation. Neuropathologic
      evaluation reveals significant cerebral cortical atrophy, delayed myelination and
      Alzheimer type II astrocytosis. Using an animal model of congenital OTC
      deficiency, the sparse fur (spf) mouse, studies reveal convincing evidence of a
      loss of forebrain cholinergic neurons in this condition. Evidence includes (i)
      reduced activities of the cholinergic nerve terminal enzyme choline
      acetyltransferase (ChAT), (ii) a 25% loss of ChAT immunostaining, (iii) reduced
      high affinity transport of [3H]choline by cortical synaptosomes and (iv) a
      selective reduction in densities of presynaptic muscarinic M2 binding sites, in
      spf mouse brain compared to controls. A partial correction of the cholinergic
      deficit was observed following treatment with acetyl-L-carnitine. Possible
      mechanisms responsible for cholinergic neuronal loss in congenital OTC deficiency
      include decreased synthesis of the ChAT substrate acetyl CoA, impaired cerebral
      energy metabolism and NMDA receptor-mediated excitotoxicity. Loss of forebrain
      cholinergic neurons is consistent with the severe cognitive impairment
      characteristic of congenital OTC deficiency.

PMID- 10885543
TI  - Cholesterol's role in atherosclerosis.

PMID- 10885544
TI  - A Pavlovian in spirit: Richard Annells Champion (1925-1999).

PMID- 10885540
TI  - The cholinergic neuronal phenotype in Alzheimer's disease.
AB  - The synthesis, storage and release of acetylcholine (ACh) requires the expression
      of several specialized proteins, including choline acetyltransferase (ChAT) and
      the vesicular ACh transporter (VAChT). The VAChT gene is located within the first
      intron of the ChAT gene. This unique genomic organization permits coordinated
      activation of expression of the two genes by extracellular factors. Much less is
      known about factors that reduce the expression of the cholinergic phenotype. A
      cholinergic deficit is one of the primary features of Alzheimer's disease (AD),
      and AD brains are characterized by amyloid deposits composed primarily of A beta
      peptides. Although A beta peptides are neurotoxic, part of the cholinergic
      deficit in AD could be attributed to the suppression of cholinergic markers in
      the absence of cell death. Indeed, we and others demonstrated that synthetic A
      beta peptides, at submicromolar concentrations that cause no cytotoxicity, reduce
      the expression of cholinergic markers in neuronal cells. Another feature of AD is
      abnormal phospholipid turnover, which might be related to the progressive
      accumulation of apolipoprotein E (apoE) within amyloid plaques, leading perhaps
      to the reduction of apoE content in the CSF of AD patients. ApoE is a component
      of very low density lipoproteins (VLDL). As a first step in investigating a
      potential neuroprotective function of apoE, we determined the effects of VLDL on
      ACh content in neuronal cells. We found that VLDL increases ACh levels, and that
      it can partially offset the anticholinergic actions of A beta peptides.

PMID- 10885545
TI  - Revisiting the learning-without-awareness question in human Pavlovian autonomic
      conditioning: focus on extinction in a dichotic listening paradigm.
AB  - Numerous studies have indicated that, consistent with current "cognitive"
      accounts of information processing, human Pavlovian autonomic discrimination
      acquisition cannot occur without awareness of the CS-US relationship. However,
      extinction studies have suggested that awareness is not necessary, findings that,
      in information-processing terms, have been explained by assuming that the
      processing by the extinction stage is parallel (automatic) rather than serial
      (controlled). This explanation was tested in an 80-subject study. The first,
      acquisition phase was a standard semantic differential conditioning arrangement
      with a 96-db white noise as US, and a "long" CS-US interval of 8 s, with ten
      trials each of CS+ (paired with US) and CS- (unpaired) trials. In extinction (USs
      omitted), in order to obtain non-autonomic indices of processing and thereby test
      the information-processing account of "unaware" autonomic conditioning during
      extinction, a dichotic listening task was implemented, with the CSs presented in
      the unattended channel (ear), while the subject had to perform a semantic
      differential reaction task in an attended-to channel (other ear). In early
      extinction, the electrodermal response occurring at an interval of 9-15 s after
      CS onset (i.e., following placement of the US during acquisition) and the finger
      pulse-volume response occurring at an interval of 4-11 s after CS onset both
      showed reliable conditioning, but reaction-time and subjective-report data for
      the recognized critical words indicated serial rather than parallel processing of
      the CSs during extinction.

PMID- 10885546
TI  - Theory of the organism-environment system: IV. The problem on mental activity and
      consciousness.
AB  - The present article is an attempt to bring together the development of mental
      activity and consciousness in the framework of the organism-environment theory
      (Jarvilehto, 1998a, 1998b, 1999); the main question is how the development of
      mental activity and consciousness can be formulated if the starting point is not
      the separation of man and environment as in traditional cognitive psychology, but
      a unitary organism-environment system. According to the present formulation,
      mental activity is conceived as activity of the whole organism-environment system
      and connected to the general development of life as a specific form of an
      organism-environment system comprising neurons. The advent of consciousness is
      regarded as a result of co-operation of such organism-environment systems.
      Consciousness is based on cooperation for the achievement of common results, and
      shared by the cooperating individuals (general consciousness), although each
      individual also makes it concrete from the perspective of his/her own body in the
      act of participation in common results (personal consciousness). Language is the
      means of formation of the cooperative system in the achievement of common
      results, and it is suggested that the use of language is related more to the type
      of cooperative system and intended common results than to any symbolic
      representation of the world. It is claimed that on this basis it is possible to
      develop psychology which takes seriously the concepts of mental activity and
      consciousness in the description of human action, but does not reduce these
      concepts either to biological or social factors. The present formulation should
      be regarded more as a conceptual outline than as a full-blown theory.

PMID- 10885547
TI  - Interdisciplinary research: a philosophy, art form, artifact or antidote?
AB  - Interdisciplinary research has many faces--a philosophy, an art form, an
      artifact, and an antidote. It is all of these things because interdisciplinary
      research attempts to ask questions in ways that cut across disciplinary
      boundaries. This is not politically correct and universities especially find it
      difficult to manage interdisciplinarians and their projects. The author argues
      that interdisciplinary research has persisted as an alternative when traditional
      research approaches have failed to come up with answers to common problems.
      Interdisciplinary research will continue to survive as long as there are
      creative, risk-taking scientists who are dissatisfied with the political and
      organizational boundaries we establish around disciplines which limit our ability
      to learn about their commonalities.

PMID- 10885548
TI  - Laparoscopic surgery--effects on circulatory and respiratory physiology: an
      overview.

PMID- 10885549
TI  - Results of laparoscopic compared with open cholecystectomy.
AB  - Laparoscopic cholecystectomy was introduced in 1985 and diffused within a few
      years throughout the world. The avalanche-like spread resulted in this procedure
      not being scientifically supported by results of controlled clinical trials. By
      1997 there were just 13 randomised controlled trials and 150 prospective studies
      that followed a research protocol, while there were more than 1500 retrospective
      analyses of series of operations in a country, in a specific hospital, or by a
      specific surgeon. Comparisons with the conventional laparotomy technique and with
      minilaparotomy techniques are complicated by the fact that the variables
      compared, such as operation times, complication rates, and costs, varied over
      time.

PMID- 10885550
TI  - Laparoscopic cholecystectomy for acute cholecystitis.
AB  - Acute cholecystitis was initially considered a contra-indication for laparoscopic
      cholecystectomy, but today the laparoscopic route is generally used even for
      severe acute cholecystitis. Several studies have shown that this is possible,
      although the conversion and complication rates are high, but there are no
      randomised controlled trials that evaluate the complications and costs of this
      technique compared with conventional open techniques. The timing of a
      laparoscopic cholecystectomy for acute cholecystitis is also a matter of debate
      as well as its use in elderly patients with this condition.

PMID- 10885551
TI  - Complications of laparoscopic cholecystectomy as recorded in the Swedish
      laparoscopy registry.
AB  - The Swedish laparoscopy registry prospectively recorded 11,164 laparoscopic
      cholecystectomies during the years 1991-1993 with the aim of monitoring bile duct
      injuries and other complications of the new technique. In total 57 bile ducts
      were injured; 35 of these were merely incision of the common bile duct. Serious
      injuries with tissue loss occurred in 11 cases and clipping or electrocautery
      damage in another 11.

PMID- 10885552
TI  - Laparoscopic management of common bile duct stones.
AB  - There are various techniques available for laparoscopic exploration of the common
      bile duct, but the most widely used are pharmacological relaxation of the
      sphincter of Oddi and saline flushing, laparoscopic transcystic exploration, and
      laparoscopic choledochotomy. Altogether 1319 patients have been reported in
      retrospective and prospective uncontrolled studies with more than 50 patients in
      each. The conclusion is that it is possible to make a laparoscopic exploration of
      the common bile duct in selected cases with low morbidity and mortality. As
      surgeons gain more experience they also learn who is and who is not a suitable
      candidate for this surgical option.

PMID- 10885553
TI  - Port site metastases after laparoscopic cholecystectomy.
AB  - The true incidence of abdominal wall metastases after open or laparoscopic
      operations is unknown. The large number of reports of patients with port site
      metastases may represent publication bias, but there is a suspicion that
      recurrence of the tumour in the abdominal incision is more common after
      laparoscopic operations. The aetiology of port site metastases is not known but
      in cases of gallbladder cancer the laparoscopic handling of the tumour,
      perforation of the gallbladder, and extraction of the malignant specimen may be
      risk factors for the spread of malignant cells. These risk factors are not
      equally applicable in laparoscopic colorectal cancer operations in which the
      incidence of port site metastases seems to be lower. In addition, several other
      factors are probably involved in the development of such metastases, including
      the creation of pneumoperitoneum and the use of different gases. Laparoscopic
      cholecystectomy is contraindicated when gallbladder cancer is known or suspected
      preoperatively. When signs of malignancy are encountered during a laparoscopic
      operation it should be converted to an open procedure. If a gallbladder cancer is
      diagnosed after a completed laparoscopic operation a careful clinical follow up
      is indicated and if signs of recurrent malignancy develop in the port sites they
      should be excised, particularly as port site metastases may be the only
      manifestation of recurrent disease.

PMID- 10885554
TI  - Changing surgical principles for gastro-oesophageal reflux disease--is
      laparoscopic fundoplication justified in the light of surgical complications?
AB  - Morbidity and mortality after surgical treatment for gastro-oesophageal reflux
      disease (GORD) can be considerable. During the past decade the dynamic evolution
      of laparoscopic surgery has seen this technique applied for GORD. In this chapter
      I will discuss perioperative and postoperative morbidity and mortality. I base my
      remarks on publications from all over the world, a national questionnaire, and a
      restricted national register. Only one randomised study has been reported, which
      concluded that there was no difference between conventional open and laparoscopic
      operations. A number of non-randomised studies have reported complications and
      clinical results in the same range as previously reported after open operations.
      More than half the surgical units in Sweden do laparoscopic fundoplications. In
      the questionnaire complications were reported in >2%, but the mortality was
      extremely low, <0.2%. These complications included postoperative paraoesophageal
      herniation, perforations, and reoperations for other reasons. There is a learning
      curve before complication rates are reduced.

PMID- 10885555
TI  - Efficacy of, and quality of life after antireflux surgery.
AB  - A complete evaluation of reflux operations depends on measurements of
      preoperative and postoperative clinical symptoms such as dysphagia and heartburn,
      assessment of quality of life and objective measurements of 24-hour oesophageal
      pH monitoring and manometry. Quality of life can be measured with questionnaires
      such as the Gastrointestinal Symptom Rating Scale (GSRS), the Psychological
      General Wellbeing Index (PGWB) and the Reflux-related Visual Analogue Scale
      (RVAS). Failure of treatment is indicated by persistent symptoms such as
      heartburn, need for antisecretory medication, and new symptoms such as severe
      dysphagia. The advantages of laparoscopic operations are mainly a quick recovery
      and a good cosmetic results. Good short-term cure of symptoms is reported in 90%
      97% of patients who have laparoscopic fundoplication. The long-term clinical
      outcome is equal to or better than that of open operations. Several clinical
      studies have shown that laparoscopic fundoplication is effective in improving
      symptom ratings and the quality of life.

PMID- 10885556
TI  - The economics of laparoscopic antireflux operations compared with open surgery.
AB  - In Sweden laparoscopic antireflux surgery started in 1991, and within four years
      replaced the open procedure as the method of choice. It is, however, not yet
      settled which of the two techniques is most cost effective. To compare these two
      operations in economic terms we studied all reports up to September 1997 as well
      as the register in the epidemiological unit of the National Board of Health and
      Welfare (EpC). We found numerous reports on consecutive series of laparoscopic
      procedures, several non-randomised studies, and only one randomised prospective
      study comparing open and laparoscopic antireflux surgery. The few studies about
      the economics of antireflux surgery indicated that hospital costs were equal or
      less for the laparoscopic procedure. If one adds the costs from loss of
      production (sick leave) it will be an even more favourable outcome for the
      laparoscopic treatment. The figures from EpC showed that antireflux surgery is
      done infrequently in many surgical departments. This may have a substantial
      influence on the economic outcome as well as the effectiveness of antireflux
      surgery in Sweden. Few studies have compared open and laparoscopic methods from
      an economic perspective. As a tool for cost benefit analysis these reports are
      incomplete.

PMID- 10885557
TI  - Laparoscopic compared with open hernia surgery: complications, recurrences and
      current trends.

PMID- 10885558
TI  - Costs and benefits of laparoscopic surgery--a review of the literature.
AB  - The purpose of this paper is to look at the cost-effectiveness of laparoscopic
      surgery in relation to conventional open surgery. It focuses both on the results
      and the methods, and aims to identify the need for further studies as well as the
      appropriate methods of economic evaluation. We searched the literature and
      identified studies in which "cost" or "cost-effectiveness" was mentioned in
      relation to open and laparoscopic surgery. Laparoscopic and open surgery were
      compared for gallbladder disease, inguinal hernia and gastro-oesophageal reflux
      disease (GORD). Finally, we reviewed studies that focused on cost comparisons of
      disposable compared with reusable instruments in laparoscopic surgery. We found
      that the evidence on whether laparoscopic surgery results in lower costs for the
      health care system than open operations is not conclusive. There are, however,
      indications that it results in savings in indirect costs from reduced periods of
      sick leave. There is also an indication that reusable instruments resulted in
      lower costs for each operation than disposable instruments. We conclude that a
      prospective, randomised study is the preferred study design in the early stage of
      the development of a new technique, when it is not fully obvious what the
      indications for the new technique are. This should be considered when doing
      economic evaluations of new indications for laparoscopic surgery, for example
      appendicectomy and non-inguinal hernia repair.

PMID- 10885559
TI  - Evolution of Pacific/Asian populations inferred from HLA class II allele
      frequency distributions.
AB  - The allele frequency distributions for the HLA class II loci, DRB1, DQB1 and
      DPB1, in eight Pacific/Asian populations: Hawaiian, Samoan, Malay, Papua New
      Guinea (PNG) Highlands, and two Indonesian and PNG Lowland groups, were
      determined using high-resolution polymerase chain reaction/sequence-specific
      oligonucleotide probe (PCR/SSOP) typing methods. The allele frequency
      distributions for the HLA-DRB1 locus were determined for a third Indonesian
      population as well as for an additional Filipino population. DRB1 alleles in the
      DR2 serogroup (or allelic lineage) are very common in this region; in some
      populations, more than 50% of the alleles belong to this serogroup. The DRB1*1502
      allele is frequent in nine of the ten populations studied, reaching a frequency
      of 0.48 in one Indonesian population and among Filipinos. Extensive DR-DQ
      haplotype diversity was detected in these populations. Seven different DR2-DQB1
      haplotypes were observed in the Indonesian and PNG Lowland populations, eight in
      the PNG Highlands and ten in Malays and Filipinos. The DRB1*0410 allele, commonly
      observed in Australia, is observed in the PNG Highlands at a low frequency
      (f=0.03) and is absent in the other populations. Two additional DRB1 alleles
      commonly observed in Australia, DRB1*0405 and *1407, are also observed in the PNG
      Highlands at high frequencies (f=0.132 and 0.126), while they are rare in the PNG
      Lowlands (f=0.039 and 0.013). These alleles are generally rare or absent in the
      other populations. The DPB1*0501 allele, common in Chinese and Japanese
      populations, is most frequent in the Samoan, Hawaiian, Indonesian, and Malay
      populations, and the *0401 allele is the most frequent DPB1 allele in the PNG
      Lowlands. Both of these alleles have the same very high frequency (f=0.34) in the
      PNG Highlands. Analyses of homozygosity (the Ewens-Watterson F statistic) in
      these and other populations indicate that, while most allele frequency
      distributions are consistent with balancing selection, values of F for the
      Indonesian and Javan populations may reflect positive directional selection.
      Phylogenetic trees constructed using the allele frequencies at the DRB1 locus of
      the populations reported here, as well as those for additional Pacific, Asian,
      and Australian populations, indicate that the PNG Highland population is more
      closely related to Australian populations than to PNG Lowland populations, while
      the PNG Lowlands are more closely related to other Melanesian populations.

PMID- 10885560
TI  - Multiple mechanisms underlie HLA dysregulation in cervical cancer.
AB  - The consistent dysregulation of HLA expression in cervical neoplasia is likely to
      influence the natural history of the disease and prospects for cell-mediated
      vaccine therapies. We have studied the underlying mechanisms in eight new
      cervical cancer cell lines derived from primary tumour biopsies. At least five
      independent mechanisms leading to changes in HLA expression were seen: HLA class
      I allelic transcription but no protein; abnormal HLA class I allelic
      transcription; no HLA-B locus transcription; loss of heterozygosity (LOH); no
      gammaIFN-mediated upregulation of HLA class I expression, and/or no interferon
      gamma (gammaIFN)-mediated HLA class II induction. These were evident in different
      combinations in 7/8 cell lines showing that multiple, mostly irreversible
      mechanisms not overridden by gammaIFN, are responsible for HLA dysregulation in
      cervical neoplasia. Point mutations were responsible for lack of HLA-A2
      expression in two cases. In cell line 808, the mutation encodes a stop codon in
      exon 3; in cell line 778, mutation of the first intron acceptor site leads to use
      of an alternative AG site in exon 2, resulting in a frameshift and a stop codon
      after the translation of only 38 amino acids. Tumour cells showing specific HLA
      class I loss may have selective advantage in the face of tumour-specific
      cytotoxic T cells (CTL). Such immune escape mechanisms present a major obstacle
      for the success of CTL-mediated therapies in cervical cancer.

PMID- 10885561
TI  - Cytomegalovirus-infected neuroblastoma cells exhibit augmented invasiveness
      mediated by beta1alpha5 integrin (VLA-5).
AB  - Previously, experimental in vivo results showed that the productively and
      persistently human cytomegalovirus (HCMV)-infected neuroblastoma cell line UKF-NB
      4AD169 exhibits a more malignant phenotype than the non-infected variant UKF-NB
      4. To prove the assumption that enhanced malignancy may be due to enhanced
      invasive potential of the infected cells we studied interactions of both lines
      with monolayers of cultured endothelial cells. UKF-NB-4AD169 cells adhered to and
      transmigrated through endothelial monolayer to a significantly higher extent
      compared with UKF-NB4. Furthermore, the adhesion of UKF-NB-4AD169 but not of UKF
      NB4 resulted in focal disruption of the monolayer integrity which facilitates
      tumor cell transmigration. Blocking antibodies directed against the beta1
      integrin chain as well as beta1alpha5 on the tumor cells specifically inhibited
      adhesion in a concentration-dependent manner. When UKF-NB-4 were pretreated with
      a beta1 integrin activating antibody, focal disruption of the endothelial
      integrity also occurred. These findings lead us to suggest that HCMV infection
      activates beta1alpha5 in the host neuroblastoma cell which in turn enables these
      cells to tightly adhere to endothelial cells. In the presence of the protease
      inhibitor phenantroline, beta1alpha5-mediated adhesion was not impaired whereas
      UKF-NB4AD169-mediated endothelial monolayer permeabilization was dose dependently
      inhibited. We conclude that human cytomegalovirus infection contributes to
      augmented neuroblastoma invasiveness via adhesion of activated beta1alpha5 and
      subsequent matrix digestion by proteases.

PMID- 10885562
TI  - A unique second donor splice site in the intron 5 sequence of the HLA-A*11
      alleles results in a class I transcript encoding a molecule with an elongated
      cytoplasmic domain.
AB  - Full-length cDNA sequencing of the A*1103 allele revealed an insertion of 18 bp
      between exon 5 and 6. We hypothesized that this could be the result of
      alternative splicing. Sequencing of intron-5 of A*1101, *1102 and *1103 alleles
      demonstrated that this 18-bp insertion consisted of the 5'-end of intron 5,
      concluded by a second in-frame donor splice site. Alignment of the 5'-end intron
      5 sequence of A*1101-3 with that of A*0101, *0201 and 0301 revealed a unique
      polymorphism at position 17 of the intron (A to G) that created this second donor
      splice site. To exclude the possibility of an Epstein-Barr virus (EBV)-induced
      event, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was
      performed on both peripheral blood mononuclear cells (PBMC) and EBV-transformed b
      LcL's of several A*11-positive individuals, using primers spanning exons 5 and 6.
      Without exception, both cell types revealed two products for A*11. Densitometric
      analysis using EBV-transformed b-LcL's and PBMC indicated a ratio of
      approximately 4:1 in favor of the alternative splice product. Notably, except for
      the A*11's none of the other A-locus alleles yields this alternative splice
      product. Translation of this product will result in a protein that has an
      additional 6 amino acids in its cytoplasmic domain. This introduces a negative
      charge just behind the basic anchor residues of the cytoplasmic segment and
      results in the loss of the single potential protein kinase C phosphorylation
      site.

PMID- 10885563
TI  - CDw108 expression during T-cell development.
AB  - We recently reported a gene encoding the human CDw108, a
      glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that is
      preferentially expressed on activated T lymphocytes and erythrocytes. The present
      study investigated the expression of CDw108 on various tissues and cells,
      particularly on T cells during development. The murine CDw108 cDNA was cloned
      initially, and it was highly homologous to the human CDw108 (88.0% or 89.3%
      similarity at the nucleotide or amino acid level, respectively) or identical to
      the murine semaphorin K1/Sema7A. The CDw108 mRNA was demonstrated in a few
      tissues including thymus and brain with the highest expression coming on day 7 in
      whole embryo followed by relatively consistent expression during development.
      Cell-surface expression of the CDw108 during T-cell development was further
      examined by flow cytometry in the human umbilical cord blood and thymus. It was
      preferentially expressed on a CD34+ stem cell population of umbilical cord blood,
      and CD3dull CD34+/- CD117 (c-kit)+ CD4bright CDbright cells in the thymus that
      are involved in the stage of positive selection. These results suggest the
      contribution of CDw108 in T-cell development, especially in the stage of positive
      selection in the thymus.

PMID- 10885564
TI  - The relationship between HLA-B45 and B* 5002 in the five major U.S. population
      groups.
AB  - The antigen encoded by B*5002 differs in sequence from that encoded by B*5001
      only at amino acid residue 167 (consensus tryptophan vs. serine) which results in
      B45 serologic reactivity. To search for B*5002, the frequencies of alleles
      encoding the serologically defined B45 antigen were determined by sequence-based
      typing in 5 major U.S. populations: Caucasians, African Americans, Asians/Pacific
      Islanders, Hispanics, and Native Americans. The percent of serologically defined
      B45-positive individuals in the 5 populations ranged from 0.7-9.0%. Thirty-two
      B45-positive individuals were randomly chosen, when available, for sequence-based
      typing from each ethnic group from a database of 82,979 consecutively typed
      unrelated individuals. The B*5002 allele was most prevalent in Hispanic (22%) and
      Caucasian (9%) individuals, while conspicuously absent in African Americans. In
      addition, a new allele associated with the B45 antigenic specificity, B*4502, has
      been identified from an African American individual of Middle Eastern descent. In
      light of the continuing need to reconcile differences between relationships
      determined by the sequence homologies among alleles and relationships based on
      the serologic determinants carried by allelic products when determining the level
      of HLA match for hematopoietic stem cell transplantation, it is suggested that
      B*5002 be recognized individually from other B*50 alleles when reporting HLA-B
      typings for clinical purposes.

PMID- 10885565
TI  - Criteria to define HLA haplotype loss in human solid tumors.
AB  - Short tandem repeat (STR) markers are currently used to define loss of
      heterozygosity (LOH) of genes and chromosomes in tumors. Chromosome 6 and
      chromosome 15 STR markers are applied to define loss of HLA and related genes
      (e.g. TAP and beta2m). The number of STR identified in the HLA region is still
      increasing. In this study, seven representative STR markers covering the 6p/6q
      arms of chromosome 6 including the HLA region and two for chromosome 15 flanking
      the beta2m gene, were selected as minimally required for reliable LOH studies. A
      multiplex polymerase chain reaction (PCR) strategy is proposed when small number
      of cells are available in microdissected tumor samples.

PMID- 10885566
TI  - Susceptible locus for obese type 2 diabetes mellitus in the 5'-flanking region of
      the tumor necrosis factor-alpha gene.
AB  - We have identified three novel polymorphisms in the promoter/enhancer region of
      the tumor necrosis factor (TNF)-alpha gene. In this study we investigated the
      role of the polymorphisms in predisposition to Type 2 diabetes. The allele
      frequency of C-->T substitution at -857 tended to be higher in obese patients
      with diabetes than in lean subjects with normal glucose tolerance (0280 vs.
      0.190). This tendency was due to a significantly higher ratio of -857T
      homozygotes in the obese patients with diabetes (15%) than in lean subjects with
      normal glucose tolerance (4%). There was no significant association between
      polymorphisms at positions -863 or -1,013, and diabetes. The homozygous -857T
      allele may be associated with genetic susceptibility to type 2 diabetes in obese
      subjects.

PMID- 10885567
TI  - HLA-A*6817, identified in the Kolla Amerindians of North-West Argentina possesses
      a novel nucleotide substitution.
AB  - Analysis of HLA polymorphism of the indigenous populations of Central and South
      America has identified many alleles not seen previously in other populations. We
      have described a novel allele, B*5113, previously in a Kolla Amerindian
      individual from North-West Argentina. Here we present a second novel allele from
      this population: A*6817, which differs from its closest neighbour A*68012 by a
      single substitution at nucleotide 419. This substitution of adenosine 419 A*68012
      for thymidine in A*6817 results in a novel amino acid change (aspartate to
      valine) at residue 116.

PMID- 10885568
TI  - Novel HLA-B*15 alleles identified in potential marrow donors.
AB  - Several methods for low-resolution class I typing of potential bone marrow donors
      are available. The National Marrow Donor Program (NMDP) has initiated pilot
      projects for large-scale DNA-based class I typing to initially characterize
      donors. Sequence-specific oligonucleotide probe hybridization and sequence
      specific primer polymerase chain reaction (PCR) screening of 3,500 NMDP potential
      donors suggested the presence of variants of known HLA-B*15 variants in 3 donors.
      PCR products encompassing HLA-B locus exons 1 through 3 were prepared and
      subcloned. Sequencing revealed 3 alleles differing from known HLA-B*15 alleles by
      nucleotide substitutions resulting in predicted novel HLA-B antigens. The new
      alleles occur in distinct ethnic groups. These findings further illustrate the
      substantial genetic variation present at the HLA-B locus within human
      populations.

PMID- 10885569
TI  - Identification of a novel HLA-B46 allele, B*4602, in Japanese.
AB  - The B*4602 was identified in a healthy Japanese donor. The B46 variant antigen
      differed serologically from B46. The nucleotide sequence of B*4602 differed from
      that of B*4601 by a single base (from A to G) at position 293 in exon 2. The
      substitution changed the amino acid Asp at position 74 to Gly. The gene frequency
      of B*4602 in the Japanese population is extremely low. The presumed haplotype of
      B*4602 was HLA-A2-Cw1-B*4602-DRB1*09. This is the first report of polymorphism of
      the B46 antigen.

PMID- 10885570
TI  - A new allele, HLA-B*1555, identified in an African patient awaiting bone marrow
      transplantation.
AB  - Human HLA genes exhibit extreme polymorphism, the extent of which is emphasised
      by the identification of an ever increasing number of new alleles by DNA-based
      typing strategies. Here we describe a novel allele, belonging to the HLA-B*15
      group, which was identified in an African patient awaiting a bone marrow
      transplant This individual was shown to exhibit two HLA-B alleles, B*5301 and a
      new allele which has been named B*1555. B*1555 differs from B*1531 in exon 3 by a
      single nucleotide substitution. This substitution results in a change in the
      amino acid residue at position 97, which is located within the beta-pleated sheet
      region of the HLA molecule.

PMID- 10885571
TI  - HLA-DR51 expression failure caused by a two-base deletion at exon 2 of a DRB5
      null allele (DRB5*0110N) in a Spanish gypsy family.
AB  - Here we describe a new HLA class II null allele at the DRB5 gene. Serologic HLA
      typing of a Spanish gypsy family rendered the following paternal haplotype: A2
      Cblk-B52-Bw4-DR15-DQ5. However, DNA typing demonstrated the presence of a DRB5
      gene in the haplotype DRB1*1502-DRB5*0102-DQB1*05031. Complete DRB5 cDNA
      sequencing revealed a DRB5*0102 allele with a deletion of two nucleotides at exon
      2 (239-240) in codon 80. This change generates a frame shift leading to a stop
      codon at position 86, and could explain the lack of DR51 protein at the cell
      surface. This is the second DRB5 null allele described together with DRB5*0108N,
      raising the number of HLA alleles with an expression disorder.

PMID- 10885572
TI  - The nucleotide sequence of a new DMB allele, DMB*0106.
AB  - The HLA-DM genes (DMA and DMB) are encoded in the major histocompatibility
      complex (MHC) on human chromosome 6. They are involved in the loading of
      antigenic peptide onto class II molecules as part of the class II antigen
      processing and -presentation pathway. During a study of Oriental subjects (11
      Chinese and 26 Japanese subjects), one Chinese subject was identified as having a
      new DMB allele using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). This was confirmed with sequencing. The new allele was
      found to have Glu (GAG) and Thr (ACT) at positions 144 and 179 respectively. This
      was a previously unpublished combination of polymorphic sites, and was submitted
      to GenBank and assigned the accession number AF072680, and named HLA-DMB*0106.

PMID- 10885573
TI  - Identification of a novel HLA-Cw*05 allele, Cw*0503.
AB  - HLA-Cw*05 is one of the least polymorphic subgroups of HLA-C; so far only two
      alleles, namely Cw*0501 and Cw*0502, have been reported. We report here the
      identification of a third allele, Cw*0503, in a Caucasian individual. Cw*0503 is
      closely related to Cw*0501 with only six nucleotide substitutions clustering over
      a fragment of 48 nucleotides at the beginning of exon 4. All these six
      substitutions at the same positions have been found only in HLA-B*44 alleles,
      suggesting that Cw*0503 is a result of recombination between Cw*0501 and one of
      B*44 alleles.

PMID- 10885574
TI  - Nomenclature for factors of the HLA system, update January 2000. WHO Nomenclature
      Committee for Factors of the HLA System.

PMID- 10885575
TI  - Serendipities in the study of extracellular matrix macromolecules.

PMID- 10885577
TI  - Mammalian skeletogenesis and extracellular matrix: what can we learn from
      knockout mice?
AB  - Formation of the vertebrate skeleton and the proper functions of bony and
      cartilaginous elements are determined by extracellular, cell surface and
      intracellular molecules. Genetic and biochemical analyses of human heritable
      skeletal disorders as well as the generation of knockout mice provide useful
      tools to identify the key players of mammalian skeletogenesis. This review
      summarises our recent work with transgenic animals carrying ablated genes for
      cartilage extracellular matrix proteins. Some of these mice exhibit a lethal
      phenotype associated with severe skeletal defects (type II collagen-null,
      perlecan-null), whereas others show mild (type IX collagen-null) or no skeletal
      abnormalities (matrilin-1-null, fibromodulin-null, tenascin-C-null). The
      appropriate human genetic disorders are discussed and contrasted with the
      knockout mice phenotypes.

PMID- 10885576
TI  - Elastic and collagenous networks in vascular diseases.
AB  - Supravalvular aortic stenosis (SVAS), Marfan syndrome (MFS) and Ehlers-Danlos
      syndrome type IV (EDS IV) are three clinical entities characterized by vascular
      abnormalities that result from mutations of structural components of the
      extracellular matrix (ECM). Analyses of naturally occurring human mutations and
      of artificially generated deficiencies in the mouse have provided insights into
      the pathogenesis of these heritable disorders of the connective tissue. SVAS is
      associated with haploinsufficiency of elastin, one of the two major components of
      the elastic fibers. SVAS is characterized by narrowing of the arterial lumen due
      to the failure of regulation of cellular proliferation and matrix deposition.
      Mutations in fibrillin 1 are the cause of dissecting aneurysm leading to rupture
      of the ascending aorta. Fibrillin-1 is the building block of the microfibrils
      that span the entire thickness of the aortic wall and are a major component of
      the elastic fibers that reside in the medial layer. The vascular hallmark of EDS
      IV is rupture of large vessels. The phenotype is caused by mutations in type III
      collagen. The mutations ultimately affect the overall architecture of the
      collagenous network and the biomechanical properties of the adventitial layer of
      the vessel wall. Altogether, these genotype-phenotype correlations document the
      diversified contributions of distinct extracellular macroaggregates to the
      assembly and function of the vascular matrix.

PMID- 10885579
TI  - Collagen XVIII/endostatin structure and functional role in angiogenesis.
AB  - The angiogenesis inhibitor endostatin is a 20 kDA C-terminal fragment of collagen
      XVIII, a proteoglycan/collagen found in vessel walls and basement membranes. The
      endostatin fragment was originally identified in conditioned media from a murine
      endothelial tumor cell line. Endostatin inhibits endothelial cell migration in
      vitro and appears to be highly effective in murine in vivo studies. The molecular
      mechanisms behind the inhibition of angiogenesis have not yet been elucidated.
      Studies of the crystal structure of endostatin have shown a compact globular
      fold, with one face particularly rich in arginine residues acting as a heparin
      binding epitope. It was initially suggested that zinc binding was essential for
      the antiangiogenic mechanism but later studies indicate that zinc has a
      structural rather than a functional role in endostatin. The generation of
      endostatin or endostatin-like collagen XVIII fragments is catalyzed by
      proteolytic enzymes, including cathepsin L and matrix metalloproteases, that
      cleave peptide bonds within the protease-sensitive hinge region of the C-terminal
      domain. The processing of collagen XVIII to endostatin may represent a local
      control mechanism for the regulation of angiogenesis.

PMID- 10885578
TI  - The pleiotropic effects of fibroblast growth factor receptors in mammalian
      development.
AB  - In recent years the study of fibroblast growth factor receptors (FGFRs) in normal
      development and human genetic disorders has increased our understanding of some
      complex cellular processes. At least fifteen genetic disorders result from
      mutations within FGFR genes including skeletal dysplasias such as Apert syndrome
      and achondroplasia. In vitro experiments and the generation of animal models
      indicate that these mutations result in activation of the receptors and that
      FGFRs act as negative regulators of bone growth. FGFRs also play a role in wound
      healing and cancer. In this article, we review the expression of FGFRs in human
      development, the phenotypes resulting from FGFR mutations, and recent data
      identifying pathways downstream of the activated receptors.

PMID- 10885580
TI  - Down-regulated RPS3a/nbl expression during retinoid-induced differentiation of HL
      60 cells: a close association with diminished susceptibility to actinomycin D
      stimulated apoptosis.
AB  - The efficacy of anticancer agents significantly depends on the differential
      susceptibility of undifferentiated cancer cells and differentiated normal cells
      to undergo apoptosis. We previously found that enhanced expression of RPS3a/nbl,
      which apparently encodes a ribosomal protein, seems to prime cells for apoptosis,
      while suppressing such enhanced expression triggers cell death. The present study
      found that HL-60 cells induced to differentiate by all-trans retinoic acid did
      not undergo apoptosis following treatment with actinomycin D whereas
      undifferentiated HL-60 cells were highly apoptosis-susceptible, confirming
      earlier suggestions that differentiated cells have diminished apoptosis
      susceptibility. Undifferentiated HL-60 cells highly expressed RPS3a/nbl whereas
      all-trans retinoic acid -induced differentiated cells exhibited markedly reduced
      levels, suggesting that apoptosis-resistance of differentiated cells could be due
      to low RPS3a/nbl expression. Down-regulation of enhanced RPS3a/nbl expression was
      also observed in cells induced to differentiate with the retinoid 4-[(E)-2
      (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl)-1- propenyl]benzoic acid
      without any significant induction of cell death. While down-regulation of
      RPS3a/nbl expression during differentiation did not apparently induce apoptosis,
      RPS3a/nbl antisense oligomers triggered death of undifferentiated HL-60 cells,
      but not of retinoid-induced differentiated cells. It therefore seems that while
      down-regulation of enhanced RPS3a/nbl expression can induce apoptosis in
      undifferentiated cells, down-regulation of enhanced RPS3a/nbl expression during
      differentiation occurs independently of apoptosis, and could be regarded as
      reverting the primed condition to the unprimed (low RPS3a/nbl) state.

PMID- 10885581
TI  - Recycling of importin alpha from the nucleus is suppressed by loss of RCC1
      function in living mammalian cells.
AB  - We previously reported that the nuclear import of substrates containing SV40 T
      antigen nuclear localization signal (NLS) was suppressed in a temperature
      sensitive RCC1 mutant cell line, tsBN2, at nonpermissive temperature. Moreover,
      it was shown that import into wild type BHK21 cell-derived nuclei gradually
      decreased in heterokaryons between the tsBN2 and BHK21 cells, although the BHK21
      nuclei retained wild type RCC1 and should contain RanGTP (Tachibana et al.,
      1994). In this study, it was found that in the heterokaryons cultured at non
      permissive temperature, endogenous importin alpha was not detected
      immunocytochemically in the cytoplasm or BHK21 nuclei but only in the tsBN2
      nuclei, suggesting that importin alpha cannot be exported from the RCC1-depleted
      nuclei. In fact, importin alpha microinjected into the nucleus of tsBN2 cells at
      non-permissive temperature remained in the nucleus. These results strongly
      support the hypothesis that the recycling of importin alpha from the nucleus
      requires nuclear RanGTP. Moreover, it was found that cytoplasmic injection of
      importin alpha restored the import of SV40 T-NLS substrates in the BHK21 nuclei
      but not the tsBN2 nuclei in the heterokaryons. This indicates that the decrease
      of importin alpha from the cytoplasm in the heterokaryons leads to a suppression
      of the efficiency of nuclear import of the T-NLS substrate and provides support
      for the view that nuclear RanGTP is essential for the nuclear entry of the
      substrates.

PMID- 10885582
TI  - Ca2+ signal is generated only once in the mating pheromone response pathway in
      Saccharomyces cerevisiae.
AB  - The mating pheromone, alpha-factor, of the yeast Saccharomyces cerevisiae binds
      to the heterotrimeric G protein-coupled cell surface receptor of MATa cells and
      induces cellular responses necessary for mating. In higher eukaryotic cells, many
      hormones and growth factors rapidly mobilize a second messenger, Ca2+, by means
      of receptor-G protein signaling. Although striking similarities between the
      mechanisms of the receptor-G protein signaling in yeast and higher eukaryotes
      have long been known, it is still uncertain whether the pheromone rapidly
      mobilizes Ca2+ necessary for early events of the pheromone response. Here we
      reexamine this problem using sensitive methods for detecting Ca2+ fluxes and
      mobilization, and find no evidence that there is rapid Ca2+ influx leading to a
      rapid increase in the cytosolic free Ca2+ concentration. In addition, the yeast
      PLC1 deletion mutant lacking phosphoinositide-specific phospholipase C, a key
      enzyme for generating Ca2+ signals in higher eukaryotic cells, responds normally
      to the pheromone. These findings suggest that the receptor-G protein signaling
      does not utilize Ca2+ as a second messenger in the early stage of the pheromone
      response pathway. Since the receptor-G protein signaling does stimulate Ca2+
      influx after early events have finished and this stimulation is essential for
      late events in the pheromone response pathway [Iida et al., (1990) J. Biol.
      Chem., 265: 13391-13399] Ca2+ may be used only once in the signal transduction
      pathway in unicellular eukaryotes such as yeast.

PMID- 10885583
TI  - Stroma-dependent maintenance of cytokine responsive hematopoietic progenitor
      cells derived from long-term bone marrow culture.
AB  - Hematopoietic cells maintained for long periods on primary cultures of bone
      marrow stromal cells formed cobblestone colonies (Dexter's long-term bone marrow
      culture, LTBC). These stably maintained hematopoietic cells (for 4 months) were
      transferred to a coculture on an established spleen stromal cell line (MSS62),
      and maintained under stromal cell layer, where they retained their invasive
      ability in the restricted space between the stromal cell layer and culture
      substratum (DFC culture). DFC contained lineage-negative (Lin-), c-Kit+, Sca-1-
      cells and spontaneously produced Mac-1+, Gr-1+ cells. DFC could not grow in the
      absence of MSS62 stromal cells, although, GM-CSF, IL-3, or IL-7 stimulated its
      growth. Production of granulocyte and monocytic cells was maintained by GM-CSF or
      IL-3 while it was decreased by IL-7. RT-PCR analysis showed that the IL-7
      responsive cell population expressed early lymphoid markers (Ikaros, Pax-5, Oct
      2, Rag-1, TdT, IL-7R and Imu), while lacking expression of receptors for G-CSF (G
      CSFR) and for M-CSF (M-CSFR), or myeloperoxidase (MPO). These results suggested
      that DFC simultaneously contained lymphoid-committed progenitors and myeloid
      committed progenitors, and that cytokines may expand their responding progenitor
      cells under the influence of signals provided by the stromal cells. Such a
      stromal cell-dependent culture system may be useful to analyze the switching
      mechanism from constitutive to inducible hematopoiesis in vitro.

PMID- 10885584
TI  - Clinical pharmacokinetics of mirtazapine.
AB  - Mirtazapine is the first noradrenergic and specific serotonergic antidepressant
      ('NaSSA'). It is rapidly and well absorbed from the gastrointestinal tract after
      single and multiple oral administration, and peak plasma concentrations are
      reached within 2 hours. Mirtazapine binds to plasma proteins (85%) in a
      nonspecific and reversible way. The absolute bioavailability is approximately
      50%, mainly because of gut wall and hepatic first-pass metabolism. Mirtazapine
      shows linear pharmacokinetics over a dose range of 15 to 80mg. The presence of
      food has a minor effect on the rate, but does not affect the extent, of
      absorption. The pharmacokinetics of mirtazapine are dependent on gender and age:
      females and the elderly show higher plasma concentrations than males and young
      adults. The elimination half-life of mirtazapine ranges from 20 to 40 hours,
      which is in agreement with the time to reach steady state (4 to 6 days). Total
      body clearance as determined from intravenous administration to young males
      amounts to 31 L/h. Liver and moderate renal impairment cause an approximately 30%
      decrease in oral mirtazapine clearance; severe renal impairment causes a 50%
      decrease in clearance. There were no clinically or statistically significant
      differences between poor (PM) and extensive (EM) metabolisers of debrisoquine [a
      cytochrome P450 (CYP) 2D6 substrate] with regard to the pharmacokinetics of the
      racemate. The pharmacokinetics of mirtazapine appears to be enantioselective,
      resulting in higher plasma concentrations and longer half-life of the (R)-(-)
      enantiomer (18.0 +/-2.5h) compared with that of the (S)-(+)-enantiomer (9.9+/-3.
      lh). Genetic CYP2D6 polymorphism has different effects on the enantiomers. For
      the (R)-(-)-enantiomer there are no differences between EM and PM for any of the
      kinetic parameters; for (S)-(+)-mirtazapine the area under the concentration-time
      curve (AUC) is 79% larger in PM than in EM, and a corresponding longer half-life
      was found. Approximately 100% of the orally administered dose is excreted via
      urine and faeces within 4 days. Biotransformation is mainly mediated by the
      CYP2D6 and CYP3A4 isoenzymes. Inhibitors of these isoenzymes, such as paroxetine
      and fluoxetine, cause modestly increased mirtazapine plasma concentrations (17
      and 32%, respectively) without leading to clinically relevant consequences.
      Enzyme induction by carbamazepine causes a considerable decrease (60%) in
      mirtazapine plasma concentrations. Mirtazapine has little inhibitory effects on
      CYP isoenzymes and, therefore, the pharmacokinetics of coadministered drugs are
      hardly affected by mirtazapine. Although no concentration-effect relationship
      could be established, it was found that with therapeutic dosages of mirtazapine
      (15 to 45 mg/day), plasma concentrations range on average from 5 to 100 microg/L.

PMID- 10885585
TI  - Clinical pharmacokinetics of 2'-deoxy-2'-methylidenecytidine (DMDC), a
      deoxycytidine analogue antineoplastic agent.
AB  - This article reviews the clinical pharmacokinetics of a deoxycytidine analogue of
      cytarabine, 2'-deoxy-2'-methylidenecytidine (DMDC). DMDC belongs to the
      antimetabolite class of anticancer drugs and is phosphorylated into its active,
      triphosphate, form within the tumour cell. Cancer cell death appears to be a
      result of the impairment of DNA synthesis by the triphosphate form. DMDC
      undergoes deamination to the inactive 2'-deoxy-2'-methylideneuridine (DMDU), its
      main plasma metabolite. Following intravenous administration at 30 to 450 mg/m2,
      DMDC has low systemic clearance (10 to 15 L/h/m2), moderate volume of
      distribution (nominally similar to total body water) and a short elimination half
      life of between 2 and 6 hours. Renal clearance of DMDC accounts for approximately
      30 to 50% of total clearance. Following oral administration of DMDC at 12 to 50
      mg/m2, mean maximum DMDC plasma concentrations are within the 100 to 400 microg/L
      range and are generally reached within 2 hours. Oral bioavailability of DMDC is
      in the order of 40%, largely as a result of first-pass metabolism in the gut and
      liver. This first-pass effect results in considerable interpatient variability in
      systemic exposure to DMDC after oral administration. The systemic availability of
      DMDC is proportional to the administered dose and, although there was evidence
      that systemic exposure to DMDC decreased on repeated administration, there are no
      excessive time-dependent changes in systemic exposure to DMDC. Following oral
      administration, DMDC is metabolised in the gut wall and liver by deamination to
      DMDU. The kidneys eliminate DMDC and DMDU, with up to 50% of the administered
      dose recovered in urine, on average, as parent drug and metabolite. Dose
      escalation to the maximum tolerated dose was facilitated by a pharmacokinetically
      guided dose escalation strategy. DMDC has shown activity in non-small-cell lung
      cancer and colorectal cancers following oral administration. Several tumour
      responses are observed at the highest doses of DMDC, indicating a possible dose
      response relationship with this drug. The main clinical adverse event of DMDC
      therapy is myelotoxicity. The haematological toxicity of DMDC was schedule
      dependent; twice daily administration was associated with greater toxic effects
      than a once daily regimen. A pharmacokinetic-pharmacodynamic model characterised
      the relationship between plasma DMDC concentrations and the time-dissociated
      toxicity. This model-dependent approach may be used to predict the consequences
      of as-yet-untested therapy as well as relating acceptable risks of haematological
      toxicity to target drug exposure.

PMID- 10885586
TI  - Induction of drug metabolising enzymes: pharmacokinetic and toxicological
      consequences in humans.
AB  - Currently, 5 different main mechanisms of induction are distinguished for drug
      metabolising enzymes. The ethanol type of induction is mediated by ligand
      stabilisation of the enzyme, but the others appear to be mediated by
      intracellular 'receptors'. These are the aryl hydrocarbon (Ah) receptor, the
      peroxisome proliferator activated receptor (PPAR), the constitutive androstane
      receptor (CAR, phenobarbital induction) and the pregnane X receptor [PXR,
      rifampicin (rifampin) induction]. Enzyme induction has the net effect of
      increasing protein levels. However, many inducers are also inhibitors of the
      enzymes they induce, and the inductive effects of a single drug may be mediated
      by more than one mechanism. Therefore, it appears that every inducer has its own
      pattern of induction; knowledge of the main mechanism is often not sufficient to
      predict the extent and time course of induction, but may serve to make the
      clinician aware of potential dangers. The possible pharmacokinetic consequences
      of enzyme induction depend on the localisation of the enzyme. They include
      decreased or absent bioavailability for orally administered drugs, increased
      hepatic clearance or accelerated formation of reactive metabolites, which is
      usually related to local toxicity. Although some severe drug-drug interactions
      are caused by enzyme induction, most of the effects of inducers are not detected
      in the background of nonspecific variation. For any potent inducer, however, its
      addition to, or withdrawal from, an existing drug regimen may cause pronounced
      concentration changes and should be done gradually and with appropriate
      monitoring of therapeutic efficacy and adverse events. The toxicological
      consequences of enzyme induction in humans are rare, and appear to be mainly
      limited to hepatoxicity in ethanol-type induction.

PMID- 10885588
TI  - Pharmacokinetics and blood pressure response of losartan in end-stage renal
      disease.
AB  - BACKGROUND: Losartan is a selective angiotensin AT1 receptor antagonist currently
      employed in the management of essential hypertension. This compound is in common
      use in populations with renal failure and end-stage renal disease (ESRD).
      OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of losartan
      in patients with ESRD in order to establish administration guidelines. METHODS:
      Patients were administered losartan 100 mg/day for 7 days, and after the seventh
      and final dose pharmacokinetic parameters were determined for both losartan and
      its active metabolite E-3174. During the study, the haemodialytic clearances of
      losartan and E-3174 were measured during a standard 4-hour dialysis session.
      Neurohumoral and biochemical changes were assessed during losartan
      administration. RESULTS: The pharmacokinetics of losartan and E-3174 in
      haemodialysis patients did not alter to a clinically significant level. Losartan
      administration was accompanied by a decline in plasma aldosterone level as well
      as by an increase in plasma renin activity. Losartan administration resulted in a
      decline in plasma uric acid level, despite the fact that the study participants
      had no residual renal function. Losartan and E-3174 were not dialysable.
      CONCLUSIONS: The pharmacokinetics of losartan and E-3174 are minimally altered in
      ESRD; thus, dosage adjustment is not required in the presence of advanced
      dialysis-dependent renal failure. In addition, postdialysis supplementation is
      not required for losartan because of the negligible dialysability of losartan and
      E-3174.

PMID- 10885587
TI  - Pharmacokinetic-Pharmacodynamic Modelling of the antipyretic effect of two oral
      formulations of ibuprofen.
AB  - OBJECTIVE: To analyse the population pharmacokinetic-pharmacodynamic
      relationships of racemic ibuprofen administered in suspension or as effervescent
      granules with the aim of exploring the effect of formulation on the relevant
      pharmacodynamic parameters. DESIGN: The pharmacokinetic model was developed from
      a randomised, cross-over bioequivalence study of the 2 formulations in healthy
      adults. The pharmacodynamic model was developed from a randomised, multicentre,
      single dose efficacy and safety study of the 2 formulations in febrile children.
      PATIENTS AND PARTICIPANTS: Pharmacokinetics were studied in 18 healthy volunteers
      aged 18 to 45 years, and pharmacodynamics were studied in 103 febrile children
      aged between 4 and 16 years with bodyweight 225kg. METHODS: The pharmacokinetic
      study consisted of two 1-day study occasions, each separated by a 1-week washout
      period. On each occasion ibuprofen 400mg was administered orally as suspension or
      granules. The time course of the antipyretic effect was evaluated in febrile
      children receiving a single oral dose of 7 mg/kg in suspension or 200 or 400mg as
      effervescent granules. During the pharmacodynamic analysis, the predicted typical
      pharmacokinetic profile (based on the pharmacokinetic model previously developed)
      was used. RESULTS: The disposition of ibuprofen was described by a 2-compartment
      model. No statistical differences (p > 0.05) were found between the 2
      formulations in the distribution and elimination parameters. Absorption of
      ibuprofen from suspension was adequately described by a first-order process;
      however, a model with 2 parallel first-order input sites was used for the drug
      given as effervescent granules, leading to time to reach maximum drug
      concentration (tmax) values of 0.9 and 1.9 hours for suspension and granules,
      respectively. The time course of the antipyretic effect was best described using
      an indirect response model. The estimates (with percentage coefficients of
      variation in parentheses) of Emax (maximum inhibition of the zero-order synthesis
      rate of the factor causing fever), EC50 (plasma concentration eliciting half of
      Emax), n (slope parameter) and k(out) (first order rate constant of degradation)
      were 0.055 (10), 6.16 (14) mg/L, 2.71 (18) and 1.17 (23) h(-1), respectively,
      where To is the estimate of the basal temperature, 38.8 (1) degrees C. No
      significant (p > 0.05) covariate effects (including pharmaceutical formulation)
      were detected in any of the pharmacodynamic parameters. CONCLUSIONS: Because of
      the indirect nature of the effect exerted by ibuprofen, the implications of
      differences found in the plasma drug concentration profiles between suspension
      and effervescent granules are less apparent in the therapeutic response.

PMID- 10885589
TI  - On the option interpretation of rational harvesting planning.
AB  - We consider the determination of the harvesting strategy maximizing the present
      expected value of the cumulative yield from the present up to extinction. By
      relying on a combination of stochastic calculus, ordinary nonlinear programming,
      and the classical theory of diffusions, we show that if the underlying population
      evolves according to a logistic diffusion subject to a general diffusion
      coefficient, then there is a single threshold density at which harvesting should
      be initiated in a singular fashion. We derive the condition which uniquely
      determines the threshold and show that harvesting should be initiated only when
      the option value of further preserving another individual falls below its
      opportunity cost. In this way, we present a real option interpretation of
      rational harvesting planning. We also consider the comparative static properties
      of the value of the harvesting opportunity and state a set of usually satisfied
      conditions under which increased stochastic fluctuations (demographic or
      environmental) decrease the expected cumulative yield from harvesting and
      increase the optimal harvesting threshold, thus postponing the rational exercise
      of the irreversible harvesting decision.

PMID- 10885590
TI  - Patterns of evolutionarily stable strategies: the maximal pattern conjecture
      revisited.
AB  - A conflict is defined by a set of pure strategies [1,..., n] and a payoff matrix,
      and may have many evolutionarily stable strategies (ESSs). A collection of
      subsets of the set of pure strategies is called a pattern. If there is an n x n
      matrix which has ESSs whose supports match those of the pattern, then that
      pattern is said to be attainable. Much of the work on patterns of ESSs relied
      upon an unproved conjecture. Subject to some relaxation of the definition of
      attainability, this conjecture is proved.

PMID- 10885591
TI  - Periodical cicadas.
AB  - The evolution of periodicity and synchronicity of magical cicadas is studied by
      means of mathematical models.

PMID- 10885592
TI  - On the comparative static properties of the expected population density in the
      presence of stochastic fluctuations.
AB  - We consider the impact of increased stochastic fluctuations on the expected
      density of an unstructured population evolving according to a regular diffusion
      process subject to a concave expected growth rate. By relying on the flow nature
      of the solutions of stochastic differential equations and Girsanov's theorem, we
      demonstrate that typically increased volatility decreases the expected future
      population density. As a consequence, we are able to characterize the sensitivity
      of the expected population density with respect to changes in the diffusion
      coefficient measuring the size of the stochastic fluctuations. We provide both
      qualitative and quantitative information about the consequences of a mis
      specified volatility structure and, especially, of a deterministic approximation
      to stochastic population growth. We also consider the effect of uncertainty in
      the initial density and demonstrate that the sign of the relationship between the
      expected population density and initial uncertainty is unambiguosly negative.

PMID- 10885593
TI  - Model reduction by extended quasi-steady-state approximation.
AB  - We extend the quasi-steady-state approximation (QSSA) with respect to the class
      of differential systems as well as with respect to the order of approximation. We
      illustrate the first extension by an example which cannot be treated in the frame
      of the classical approach. As an application of the second extension we prove
      that the trimolecular autocatalator can be approximated by a fast bimolecular
      reaction system. Finally we describe a class of singularly perturbed systems for
      which a higher order QSSA can easily be obtained.

PMID- 10885594
TI  - A mathematical model for the phase of sexual reproduction in monogonont rotifers.
AB  - Recently, the optimal sex allocation in monogonont rotifers is studied, and, as a
      closely related question, the relative frequencies of the relevant types of
      mictic females. The authors focus on the evolution of the age at which young
      mictic females lose their fertilization susceptibility and they address the
      threshold age of fertilization that maximizes resting egg production. Assuming
      that a stationary population is achieved, with stable age distribution, they
      obtain their results, without knowing the stationary population. Our aim is to
      study this problem in the framework of the theory of nonlinear age-dependent
      population dynamics developed by G. F. Webb, which is more appropriate from the
      mathematical point of view and permits to us to obtain analytically the
      stationary population and consequently it is analytically shown that a threshold
      age of fertilization equal to the age of maturation is not an ESS, despite the
      fact that then the production of resting eggs is maximum, which has been obtained
      by simulation.

PMID- 10885595
TI  - In the aftermath of scientific fraud.

PMID- 10885596
TI  - Alternatives gain credibility.

PMID- 10885597
TI  - Removal of ovarian cysts 'may not reduce cancer risk'.

PMID- 10885598
TI  - Regional chemotherapy in the treatment of advanced pancreatic cancer--is it
      relevant?
AB  - The treatment of pancreatic cancer is still problematic for physicians. Only 15%
      of patients present with resectable tumours, and systemic chemotherapy is of
      limited effectiveness. In order to achieve higher local drug concentrations in
      the tumour without causing the side-effects of a comparable level of systemic
      treatment, regional chemotherapy has been introduced as an alternative treatment.
      Several techniques have been developed over recent years, these include: celiac
      axis infusion (CAI), CAI with microspheres or haemofiltration, aortic stop flow
      (ASF) and isolated hypoxic perfusion (IHP). Whilst several authors have reported
      improved response rates and a prolongation of median survival time, these results
      have not been confirmed by others. In addition, the incidence of side-effects and
      the rate of technical complications have been reported to be high during regional
      chemotherapy. Except for a single trial containing 14 patients, no randomised
      trial comparing systemic and regional chemotherapy has been conducted. For these
      reasons, none of the reported treatment regimens can be considered to be standard
      treatment and in order to evaluate, if regional chemotherapy is indeed superior
      to systemic chemotherapy, randomised trials must be conducted.

PMID- 10885599
TI  - FEC (5-fluorouracil, epidoxorubicin and cyclophosphamide) versus EM
      (epidoxorubicin and mitomycin-C) with or without lonidamine as first-line
      treatment for advanced breast cancer. A multicentric randomised study. Final
      results.
AB  - From May 1991 to December 1996, 326 patients with advanced metastatic breast
      cancer were enrolled in a multicentre, randomised, phase III clinical trial with
      four arms. Patients were randomised to receive chemotherapy according to the FEC
      regimen (5-fluorouracil (5-FU) 500 mg/m2, epidoxorubicin (EPI) 75 mg/m2 and
      cyclophosphamide (CFA) 500 mg/m2, intravenously (i.v.). every 3 weeks) or the EM
      regimen (EPI 75 mg/m2, i.v. every 3 weeks; mitomycin C (MMC) 10 mg/m2, i.v. every
      6 weeks) or the same regimens with the addition of lonidamine (LND) until disease
      progression (orally, thrice daily, 150+150+300 mg); a maximum of eight
      chemotherapy cycles were planned. The aim of the trial was 2-fold: to compare the
      EM regimen with the commonly used FEC regimen and to evaluate the possible role
      of the addition of LND. Patients were eligible if they had histologically proven
      breast carcinoma, metastatic or locoregional relapse with measurable and/or
      evaluable disease and were aged between 18 and 70 years: 318 patients were
      considered eligible. Patients with previous anthracycline-based adjuvant
      chemotherapy or those who relapsed within 6 months after any adjuvant
      chemotherapy regimen were excluded. Chemotherapy-related toxicity of grade > or =
      3 was manageable and there was no significant difference between the arms in
      terms of haematological side-effects. The impact on heart function was mild. No
      increased toxicity was observed in the LND arms (apart from myalgias in 27-30% of
      the cases). A significant increase in the complete response rate was observed for
      the FEC/EM + LND group (20.4%) versus the FEC/EM group (10.8%). The median
      survival time and the median time to progression for the overall series were 608
      days and 273 days, respectively; EM+/-LND achieved significantly improved
      survival and time to progression versus FEC+/-LND (P=0.01). This result was
      confirmed also when the analysis was restricted to patients previously treated
      with adjuvant CMF schedules. On the basis of these results, we conclude that EM
      may represent a valuable alternative to FEC for patients requiring a first-line
      regimen for advanced/ metastatic breast carcinoma, especially in patients
      previously treated with CMF in an adjuvant setting. Furthermore, we conclude
      that, in spite of a better complete response rate in the LND arms, as there was
      no clear advantage in time to progression or survival resulting from the addition
      of LND to the FEC or EM regimens, the routine use of LND is not warranted outside
      a clinical trial.

PMID- 10885600
TI  - High activity and tolerability demonstrated for exemestane in postmenopausal
      women with metastatic breast cancer who had previously failed on tamoxifen
      treatment.
AB  - This phase II, multicentre, open-label, clinical trial evaluated antitumoral
      efficacy, tolerability and endocrine effects following 25 mg of treatment with
      oral exemestane given daily to postmenopausal women with metastatic breast
      cancer. Eligibility criteria included oestrogen and/or progesterone positivity or
      a prior response to hormonal therapy if receptor status was unknown; prior
      failure to tamoxifen therapy; and progressive disease. Patients were divided into
      three strata: patients who did not respond to tamoxifen or progressed after
      disease stabilisation (SD) for less than 6 months (stratum 1); patients who,
      after an initial response or SD lasting at least 6 months, experienced disease
      progression whilst on tamoxifen (stratum 2); patients with recurrent metastatic
      disease during or within 12 months of discontinuing adjuvant tamoxifen (stratum
      3). Of the 137 patients who received exemestane, 4 experienced a complete
      response (CR) and 28 a partial response (PR), for an overall response rate of
      23%. Another 33 patients had SD for > or = 24 weeks, resulting in an overall
      success rate of 47%. The median time to objective response was 16.1 weeks (95%
      confidence interval (CI) 9.9-24.1). The median response duration was 69.4 weeks,
      the median duration of overall success 59.1 weeks, the median time to progression
      (TTP) 25.1 weeks and the median time to treatment failure (TTF) 24 weeks.
      Response to previous hormonal therapy had little effect on the results, except
      that there was a trend toward a higher overall success rate in patients who did
      not respond to previous hormonal therapy. After 8 weeks of therapy, serum levels
      of oestradiol (E2), oestrone (E1) and oestrone sulphate (E1S) were suppressed to
      15.2%, 9.7% and 10.7% of baseline, respectively. The most common adverse events
      of drug-related or indeterminate cause were hot flushes (14%), dizziness (9%),
      nausea (8%) and increased sweating (5%). Exemestane had a favourable effect on
      performance status and tumour-related signs and symptoms, both of which improved
      or stabilised in approximately 67% and 68% of patients respectively. Exemestane
      is a unique therapy that is highly active and well tolerated as a new treatment
      for women with metastatic breast cancer.

PMID- 10885601
TI  - Significantly lower rates of BRCA1/BRCA2 founder mutations in Ashkenazi women
      with sporadic compared with familial early onset breast cancer.
AB  - To delineate the clinical, genetic and family history attributes in Jewish
      Ashkenazi women with early onset (< 42 years) breast cancer we genotyped such
      women for the three predominant Jewish Ashkenazi mutations in BRCA1 (185delAG and
      5382insC) and BRCA2 (6174delT). The study cohort was composed of 172 women
      diagnosed with breast cancer at or before the age of 42 years, obtained from the
      oncology department registry. Mutations were identified in 54 women (31%). Of 79
      women with a positive family history for breast and/or ovarian cancer, and 93
      with no such family history, 45 (57%) and 9 (10%), respectively, were mutation
      carriers (chi2 = 46; P < 0.001). Contralateral breast cancer occurred in 15 of 54
      mutation carriers (28%) compared with 8 of 118 (7%) non-carriers (chi2= 14; P <
      0.001). Early onset breast cancer per se is a weak predictor of finding germ line
      mutation(s) in BRCA1 and BRCA2, unless associated with a positive family history
      and/or bilaterality.

PMID- 10885602
TI  - Histological response of cisplatin predicts patients' survival in oesophageal
      cancer and p53 protein accumulation in pretreatment biopsy is associated with
      cisplatin sensitivity.
AB  - The aim of this study was to evaluate whether cisplatin sensitivity relates to
      patient's prognosis in oesophageal squamous cell carcinoma and to find a useful
      chemosensitivity molecular marker. 59 oesophageal squamous cell carcinoma (SCC)
      patients received cisplatin 30 mg/m2/week treatment of two to five cycles,
      followed by oesophagectomy. We analysed retrospectively whether the histological
      effect was related to patient's prognosis. Furthermore, to evaluate the
      relationship between the effect of preoperative cisplatin treatment and p53 and
      cyclin D1 expression, we investigated p53 and cyclin D1 expression in
      pretreatment biopsy samples using an immunohistochemical analysis and compared
      the results with the histological effect to cisplatin in the resected oesophagus.
      The cases that showed immunohistochemical p53 staining in the pretreatment biopsy
      samples were resistant to cisplatin (P = 0.032). However, there was no
      relationship between cyclin D1 expression and histological effect (P = 0.230).
      Nevertheless, combined analysis of p53 and cyclin D1 can predict histological
      effect (P = 0.032). The prognosis of cisplatin-sensitive cases was significantly
      better than that of cisplatin-resistant cases (P = 0.041). Cox's multivariate
      analysis revealed that the histological effect was an independent prognostic
      factor. In contrast, p53 protein accumulation and cyclin D1 were not.
      Histological response after neoadjuvant cisplatin treatment is a prognostic
      factor for oesophageal SCC and cisplatin chemotherapy may be selected according
      to the findings of p53 and cyclin D1 expression.

PMID- 10885603
TI  - The Scottish and Manchester randomised trial of neo-adjuvant chemotherapy for
      advanced cervical cancer.
AB  - 204 eligible patients were entered into a multicentre randomised trial of neo
      adjuvant chemotherapy prior to radical radiotherapy. The aim of this study was to
      assess whether there was any survival advantage in patients undergoing
      chemotherapy and radiotherapy compared with those given radiotherapy alone.
      Patients were aged up to 70 years, performance status 0-1/2, with bulky stage
      IIb, stage III or stage IVa squamous or adenosquamous carcinoma. Three cycles of
      methotrexate 100 mg/m2 and cisplatin 50 mg/m2 were given at 2-weekly intervals
      before radical radiotherapy. 104 eligible patients received the combination
      treatment and 100 radiotherapy only. The two arms of the study were well balanced
      for tumour and patient characteristics. The response rate to chemotherapy was
      49%, 33% of patients in the radiotherapy (XRT) alone arm and 45% of the
      combination arm were clinically free of tumour at the end of treatment. The
      median follow-up for surviving patients is 5.4 years (range: 11 months-8 years)
      and 84% have been followed-up for more than 4 years. 134 patients have died (68
      XRT only, 66 combined arm). The median survival RT alone was 111 weeks (95%
      confidence interval (CI) 72-151 weeks), combination arm 125 weeks (95% CI 79-170
      weeks). The estimated death ratio is 0.79 (P = 0.19, 95% CI 0.56-1.12). The
      estimated 3-year survival is 40% (95% CI 30-50%) RT only compared with 47% (95%
      CI 37-57%) in the combination arm. Acute and late toxicity of radiotherapy was
      not increased by the addition of chemotherapy.

PMID- 10885604
TI  - Clinicopathological implication of cripto expression in early stage invasive
      cervical carcinomas.
AB  - This study evaluates the expression of cripto (CR-1) protein in matched sets of
      non-neoplastic cervical epithelium, primary cervical carcinoma and metastatic
      tumours in the lymph nodes to investigate its role in uterine cervical cancer
      development and progression. Ninety-four primary cervical carcinomas in an early
      clinical stage and having the same surgical treatment modality were analysed.
      Immunoreactivity in the primary tumour was compared with that of non-neoplastic
      cervical epithelium and metastatic lymph nodes. The conventional
      clinicopathological prognostic variables for cervical carcinomas such as grade,
      tumour size, depth of invasion, parametrial and endometrial extension,
      lymphovascular space involvement and lymph node metastasis status were also
      compared with CR-1 expression of the primary tumour. Strong CR-1 immunopositivity
      was significantly correlated with tumour size and lymphovascular space
      involvement (P < 0.05). Furthermore, a significant relationship was found between
      CR-1 immunoreactivity and endometrial extension as well as parametrial
      involvement (P < 0.05). Interestingly, the CR-1 expression level was increased in
      metastatic lymph nodes compared with their primary tumours. These results suggest
      that CR-1 may contribute to disease progression in cervical carcinomas.

PMID- 10885605
TI  - p53 and Ki-ras as prognostic factors for Dukes' stage B colorectal cancer.
AB  - Mutations of the TP53 and Ki-ras genes have been reported to be of prognostic
      importance in colorectal carcinomas. An increased intracellular concentration of
      the p53 protein, although not identical to, is sometimes seen in tumours with
      TP53 mutation and has been correlated with poor prognosis in some tumour types.
      Previous colorectal cancer studies, addressing the prognostic importance of Ki
      ras mutation and TP53 aberrations, yielded contradictory results. The aim of this
      study was to determine in a clinically and therapeutically homogeneous group of
      122 sporadic Dukes' B colorectal carcinomas with a median follow-up of 67 months
      (3-144 months) whether or not p53 protein expression, TP53 mutation and K-ras
      mutation correlated with prognosis. p53 staining was performed by
      immunohistochemistry, using the monoclonal antibody DO7 on paraffin-embedded
      tissue. Mutations in exons 5-8 of the TP53 gene and in codons 12 and 13 of the K
      ras gene were assayed in paraffin-embedded tissue by the single-strand
      conformation polymorphism (SSCP) assay. Nuclear p53 staining was found in 57
      (47%) tumours. Aberrant migration patterns indicating mutation of the TP53 gene
      were found in 39 (32%) tumours. Forty-six carcinomas (38%) showed a mutation of
      the Ki-ras codons 12 or 13. In a univariate analysis, patients with wild-type
      TP53 status showed a trend towards better survival, compared with those with
      mutated TP53 (log-rank test, P = 0.051). Likewise, tumours immunohistochemically
      positive for p53 showed a worse prognosis than p53-negative tumours (P = 0.010).
      The presence or absence of mutations in Ki-ras did not correlate with prognosis
      (P = 0.703). In multivariate analysis, only p53 immunoreactivity emerged as an
      independent marker for prognosis hazard ratio (HR) = 2.16, 95% confidence
      interval (CI) 1.12-4.11, P = 0.02). Assessment of p53 protein expression is more
      discriminative than TP53 mutation to predict the outcome of Dukes' stage B
      tumours and could be a useful tool to identify patients who might benefit from
      adjuvant therapy.

PMID- 10885606
TI  - A phase II study: docetaxel as first-line chemotherapy for advanced pancreatic
      adenocarcinoma.
AB  - The aim of this study was to evaluate the efficacy of docetaxel as first-line
      chemotherapy in patients with unresectable metastatic or locally advanced
      pancreatic adenocarcinoma and to further characterise the safety and
      pharmacokinetic profiles of docetaxel. 43 patients were enrolled into this phase
      II study. Treatment consisted of a 1-h infusion of docetaxel 100 mg/m2 every 3
      weeks without premedication with corticosteroids until progression or
      unacceptable toxicity occurred. Dose modifications were planned for adverse
      events. Patients were observed for 1 month after the last docetaxel infusion, to
      document any late adverse events, with a follow-up every 3 months until death.
      Response rate and duration were the major efficacy endpoints. Response status was
      reviewed by an external independent panel. Pharmacokinetic analysis was performed
      during the first treatment cycle. 40 patients were evaluable for response, and
      all were evaluable for safety. After independent review, partial response was
      recorded in 6 patients (overall response rate, 15%; 95% confidence limit (CI),
      7.7-29.8%) and stable disease was recorded in 15 patients (38%). The median
      duration of response was 5.1 months (range: 3.1-7.2). The median pain control
      time was 4.5 months (range: 0-8) and the median time to performance status
      worsening was 2.3 months (range: 0-4.5). Most patients 40 (93.0%) received a
      relative dose intensity of more than 70% of the planned dose. The incidence and
      severity of adverse events reflected the known safety profile for docetaxel.
      Docetaxel clearance was reduced in patients with elevated concentrations of
      hepatic enzymes or bilirubin. Docetaxel is an active agent for unresectable
      metastatic or locally advanced pancreatic adenocarcinoma.

PMID- 10885607
TI  - Up-front chemotherapy with fotemustine (F) / cisplatin (CDDP) / etoposide (VP16)
      regimen in the treatment of 33 non-removable glioblastomas.
AB  - Despite combinations of surgery, radiotherapy (RT) and chemotherapy used in the
      treatment of glioblastomas, mean and median survival rates in most patients
      remain 12 months or less after diagnosis. RT and nitrosourea after surgery are
      the standard combination for glioblastomas. They may induce acquired resistance
      and, consequently, non-operable glioblastomas is a unique biological and clinical
      situation allowing evaluation of intrinsic chemosensitivity. We assess the
      fotemustine (F) (100 mg/m2 day 1)/ cisplatin (CDDP) (33 mg/m2 days 1-3)/etoposide
      (VP16) (75 mg/m2 days 1-3) monthly regimen for efficacy in non-removable
      glioblastomas at presentation. Between 1995 and 1998, 33 consecutive patients
      with symptomatic non-removable histologically proven glioblastomas were treated:
      none of them had previously received chemotherapy, irradiation or surgical
      debulking. Objective response was evaluated by contrast enhancement with magnetic
      resonance imaging (MRI) scan after each treatment. Toxicity was moderate and
      mainly haematological (grade III-IV thrombopenia = 20/171 cycles; leucopenia =
      25/171). Neutropenic fever was rare and no intracranial haemorrhages or treatment
      related deaths were noted. Nausea and vomiting (grade 1), and asymptomatic
      hearing loss were common. Peripheral neuropathy occurred in 3 patients. Objective
      response rates were 9/33 (27%) (stabilisation = 17/33). Mean survival time was
      14.4 (11.2 months in the 26 deceased patients) with a median survival of 10
      months. Median survival rates at 6 and 12 months were 88% and 42%, respectively.
      7/33 patients are still alive with median survival of 34.6 months. 7/33 (4/7
      alive) were long-term survivors (range: 19-67 months). Neoadjuvant chemotherapy
      in non-resectable patients is safe allowing delayed RT. Phase II chemotherapy
      trials should include studies with a subgroup of non-resectable tumours.

PMID- 10885608
TI  - Natural history of untreated head and neck cancer.
AB  - This paper describes the characteristics and natural history of the largest
      reported group of patients with untreated head and neck cancer. From 1953 to
      1990, 808 untreated head and neck cancer patients were followed-up until their
      death. All patients were given supportive care, but specific oncological
      treatment was not pursued secondary to advanced tumour stage, poor performance
      status and/or patients' refusal of any treatment. The overall survival ranged
      from 1 day to 53.8 months (median 3.82 months). Performance status was the most
      significant predictor of survival (P < 0.001). A subgroup of 357 patients with
      good performance status and aged less than 70 years old had a 12.9% 1-year
      survival. Approximately 50% of untreated head and neck cancer patients will die
      within 4 months of their diagnosis. However, the remaining patients can survive
      up to 4 or more years, depending on their tumour location, extent, performance
      status and level of supportive care.

PMID- 10885609
TI  - Glyceraldehyde-3-phosphate dehydrogenase gene expression in human breast cancer.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been widely used as a
      control RNA in Northern blotting and in reverse transcriptase-polymerase chain
      reaction (RT-PCR) analyses. We investigated the expression of GAPDH in a large
      series of primary breast cancers and in MCF7 human mammary epithelial breast
      cancer cells treated with oestradiol. The expression of GAPDH was quantified by a
      real-time one-step RT-PCR assay, based upon the 5' nuclease activity of Taq
      polymerase using an Abi Prism 7700 Sequence Detector System (Perkin Elmer,
      France). Using the Spearman test, GAPDH expression was found to correlate
      inversely with the age of the patients at diagnosis (P = 0.003; r = -0.147),
      oestradiol receptors (ER) (P<0.0001; r = -0.327) and progesterone receptors (PgR)
      (P < 0.0001; r = -0.206). A positive correlation was observed between GAPDH
      expression and the histo-prognostic grading (HPG) (P < 0.0001; r = 0.344).
      Moreover, the overall survival (OS) and the relapse-free survival (RFS) were
      significantly reduced in patients whose tumours showed an enhanced level of GAPDH
      expression (OS, P = 0.046; RFS, P = 0.021). Multivariate analyses demonstrated
      that GAPDH was not an independent prognostic factor. Finally, in MCF7 cells
      treated with oestradiol. a statistically significant dose-dependent increase in
      GAPDH expression was observed. These results show that GAPDH expression is
      associated with breast cancer cell proliferation and with the aggressiveness of
      tumours. The present study demonstrates that, in cancer, the use of GAPDH gene
      expression should not be used as a control RNA.

PMID- 10885610
TI  - Opposite effects of antimicrotubule agents on c-myc oncogene expression depending
      on the cell lines used.
AB  - We investigated the expression of c-myc in HT29-D4, HBL100 and Caco-2 cells
      treated with microtubule stabilising (paclitaxel) or depolymerising agents
      (vinblastine, nocodazole). After induction by epidermal growth factor (EGF), c
      myc expression decreased in HT29-D4 cells treated with all the antimicrotubule
      agents. In HBL100 and Caco-2, when microtubules were stabilised with paclitaxel,
      c-myc expression also decreased. In contrast, its expression increased after
      treatment with depolymerising agents. In both cell lines, we also observed that
      depolymerising agents alone induced c-myc expression whilst paclitaxel had no
      effect. This mRNA induction was confirmed at the protein level. In HT29-D4, no
      variation of c-myc expression was observed. Then, we showed that the increase of
      mRNA level was due to activation of gene transcription. These results indicate
      that modulation of c-myc expression varied depending on the cell lines used and
      the type of antimicrotubule agents. This work provides a potential link between
      the microtubular network and c-myc gene expression.

PMID- 10885611
TI  - Differential expression of the Ca2+ binding S100A6 protein in normal,
      preneoplastic and neoplastic colon mucosa.
AB  - The expression of calcium-binding protein S100A6 was investigated in normal colon
      tissue, in colon adenomas and in colorectal carcinomas. Using an immunoblotting
      approach we detected four S100A6 variants with Mwt of 10 kDa and pI of 5.05
      (isoform I), 5.15 (isoform II), 5.23 (isoform III) and 5.32 (isoform IV) that
      were differentially expressed in the analysed samples. The quantitative
      examination of S100A6 variant expression in 25 pairs of colorectal carcinoma and
      matched control mucosa proved a statistically significant increased abundance of
      S100A6 isoforms I (P = 0.004) and III (P = 0.025) in malignant tissue, and
      conversely, an increased level of S100A6 isoform IV in healthy tissue (P =
      0.022). The expression of isoforms I and III and the loss of isoform IV were also
      observed in colon cancer cell lines. In addition, the immunohistochemical study
      of 16 primary colorectal carcinomas revealed both in the non-paired Student t
      test and in the Mann Whitney test the statistically significant accumulation of
      S100A6 protein (P < 0.001) in the invasive margin of the tumour. The
      immunohistochemical analysis of S100A6 protein in polyps differing in clinical
      severity gave a strong staining that was maximal in dysplastic lesions. Thus, our
      results indicate a possible, statistically significant correlation (non-paired
      Student t-test P = 0.036) between S100A6 expression and colon carcinoma
      progression.

PMID- 10885612
TI  - Mechanism of antimetastatic immunopotentiation by low-dose cyclophosphamide.
AB  - We have previously reported the antimetastatic effect of a single low-dose of
      cyclophosphamide (Cy) on L-TACB rat lymphoma. The phenomenon could be adoptively
      transferred in immunocompetent rats and is abolished in nude mice, facts for
      which an immunomodulatory explanation was proposed. The aim of this paper was to
      identify the mechanism(s) by which spleen cells from Cy-treated tumour-bearing
      rats could exert this antimetastatic activity. Conditioned media obtained by
      incubation of spleen cells from Cy-treated and non-treated tumour-bearing rats,
      under specific or non-specific stimulation, were assayed to evaluate their effect
      on lymphocyte proliferation. The production of transforming growth factor beta
      (TGF-beta), interleukin-10 (IL-10) and nitric oxide (NO) by conditioned media was
      also studied. The restoration of spleen lymphoproliferative responses to normal
      levels when exposed to media conditioned by splenocytes from Cy-treated tumour
      bearing rats, together with a decreased production of suppressive cytokines TGF
      beta, IL-10 and NO, suggest an enhancement of host antimetastatic immunity
      triggered by single low-dose Cy treatment.

PMID- 10885613
TI  - Analysis of mutations in oral poliovirus vaccine by hybridization with generic
      oligonucleotide microchips.
AB  - This paper describes use of a new technology of hybridization with a micro-array
      of immobilized oligonucleotides for detection and quantification of neurovirulent
      mutants in Oral Poliovirus Vaccine (OPV). We used a micro-array consisting of
      three-dimensional gel-elements containing all possible hexamers (total of 4096
      probes). Hybridization of fluorescently labelled viral cDNA samples with such
      microchips resulted in a pattern of spots that was registered and quantified by a
      computer-linked CCD camera, so that the sequence of the original cDNA could be
      deduced. The method could reliably identify single point mutations, since each of
      them affected fluorescence intensity of 12 micro-array elements. Micro-array
      hybridization of DNA mixtures with varying contents of point mutants demonstrated
      that the method can detect as little as 10% of revertants in a population of
      vaccine virus. This new technology should be useful for quality control of live
      viral vaccines, as well as for other applications requiring identification and
      quantification of point mutations.

PMID- 10885614
TI  - Quantitative detection of RT activity by PERT assay: feasibility and limits to a
      standardized screening assay for human vaccines.
AB  - The detection of adventitious retroviruses has always been critical for assessing
      the safety concerns associated with viral vaccines. Assays for the enzymatic
      activity of reverse transcriptase (RT) are used as general methods for the
      detection of both known and unknown retroviruses. Several studies using newly
      developed ultrasensitive PCR-based RT assays reported RT activity in viral
      vaccines grown in chicken cells. Here, we have assessed the performances of such
      a PCR-based RT assay--PERT assay--for the quantitative detection of RT activity
      in vaccines. Sensitivity, linearity and reproducibility of the method were
      studied on purified RT and viral vaccines treated to release RT from potentially
      contaminant retroviruses. The level of RT activity detected in chicken cell
      derived vaccines was higher for live attenuated vaccines compared to inactivated
      ones. Contrary to other studies, RT activity was found in some mammalian cell
      derived vaccines. AZT-TP sensitivity of RT activities detected in these vaccines
      and discrimination between retroviral and RT-like activities was further
      investigated. Feasibility and limits of PERT assay as a broad-spectrum
      retroviruses detection method in vaccines are discussed.

PMID- 10885616
TI  - A TritonX-100-split virion influenza vaccine is safe and fulfills the committee
      for proprietary medicinal products (CPMP) recommendations for the European
      Community for Immunogenicity, in Children, Adults and the Elderly.
AB  - Influenza epidemics are an important cause of morbidity and mortality throughout
      the world. Current recommendations from Health Authorities emphasize annual
      immunization of people who are particularly at risk from an influenza virus
      infection; however, vaccination of working adults and of school children also has
      been shown to provide public health benefits. To give it a more advantageous
      reactogenicity profile than the diethylether-split influenza vaccines available
      previously, a split virion influenza vaccine has been produced with TritonX-100.
      In a series of clinical trials, Aventis Pasteur (formerly, Pasteur Merieux
      Connaught) tested both the safety and immunogenicity of this TritonX-100-split
      virion influenza vaccine in 566 subjects (42 children, 296 adults, and 228
      elderly adults) during three influenza seasons (1991, 1993, and 1995). The
      TritonX-100-split virion vaccine was well tolerated: no serious adverse events
      were recorded during the 21 days following immunization. Among the local
      reactions observed, mild pain, redness, or induration at the injection site were
      the most frequently reported. Fever (38.0 to 38.5 degrees C) was noted in five
      adults or elderly subjects (1%), and in two children (5%). Immunogenicity was
      determined by measuring serum haemagglutinin antibody titres specific to each
      vaccine virus strain. In each of the three vaccination campaigns, the TritonX-100
      split virion influenza vaccine fulfilled the Notes for Guidance on Harmonization
      of Requirements for Influenza Vaccines outlined by the Committee for Proprietary
      Medicinal Products (CPMP) of the European Community for an influenza virus
      vaccine (i.e., seroprotection, seroconversion, or increase of geometric mean
      titre) in all age groups.

PMID- 10885615
TI  - Evaluation and validation of virus removal by ultrafiltration during the
      production of diaspirin crosslinked haemoglobin (DCLHb).
AB  - Virus retention during ultrafiltration through A/G Technology filter cartridges
      was investigated to characterize the removal process and validate the degree of
      virus titre reduction during the filtration of red blood cell haemolysates
      performed as part of the production of diaspirin crosslinked haemoglobin (DCLHb).
      When viruses were suspended in phosphate buffered saline solution, retention was
      greater with larger sized viruses and smaller filter pore size. Virus titre was
      maintained at starting levels in the filter retentate circuit during the course
      of filtration, suggesting that the virus removal mechanism is predominantly size
      exclusion. Evaluation of specific processing variables indicated that the
      retention of phiX174 virus was increased in the presence of red blood cell
      haemolysate or at high membrane crossflow rates and transmembrane pressures,
      while the retention of EMC virus was less sensitive to variations in these
      parameters. Using these results to design a validation protocol, log reduction
      values of >7.9 were demonstrated for the retention of human immunodeficiency
      virus, pseudorabies virus and bovine viral diarrhoea viruses, 7.6 for hepatitis A
      virus, and 4.2 for porcine parvovirus. It was also shown that the retention of
      viruses was maintained during repetitive use of the same filter cartridge.

PMID- 10885617
TI  - The Pertussis Serological Potency Test. Collaborative study to
      evaluatereplacement of the Mouse Protection Test.
AB  - The Pertussis Serological Potency Test (PSPT)--based on in vitro assessment of
      the humoral immune response against Bordetella pertussis--was developed as an
      alternative for the Mouse Protection Test (MPT). A small-scale collaborative
      study was carried out in five laboratories to evaluate the relevance and
      reliability of the PSPT. The study has been divided into three separate phases,
      each with its own objective. A pilot-phase study of the antibody detection assay,
      the 18323-whole cell ELISA (WCE), was included for training purposes. Significant
      differences in absorbance and antibody concentrations between the laboratories
      were found. In the Phase I study, the intra-assay, inter-assay and inter
      laboratory precisions of the 18323-WCE were assessed. Although a precision of
      less than 20% was not always established and significant differences in antibody
      concentrations were found at random throughout the Phase I study, the ranking of
      the antibody concentrations corresponded well between the laboratories and should
      warrant a reliable potency estimation of whole cell vaccines (WCV's) in the PSPT.
      Phase II was a comparative study of the PSPT and the MPT to evaluate the
      implementation of the PSPT, to demonstrate correlation and to compare the
      reproducibility and reliability of both tests. The mean antibody concentrations
      per vaccine dose in the PSPT and the survival of mice in the MPT differed
      significantly within and between the laboratories. Nevertheless, the potencies of
      the vaccines under test estimated in both test models did not differ
      significantly (P>0.05). The PSPT and MPT correlated well in chi2-test of
      homogeneity within and between the laboratories. The potencies were similar
      (overall ratio=0.877), but the PSPT is more reproducible and reduces the chance
      of re-testing due to the smaller 95% confidence intervals. We have demonstrated
      that the PSPT is a valid model to estimate the potencies of pertussis WCV's from
      different manufacturers. Moreover, the 18323-WCE is easy to carry out and the
      intra-assay precision and antibody ranking warrants a reliable potency testing of
      pertussis WCV's in the PSPT.

PMID- 10885618
TI  - In vitro markers and biological activity in mice of seed lot strains and
      commercial Brucella melitensis Rev 1 and Brucella abortus B19 vaccines.
AB  - Four seed lots and fourteen batches of Brucella melitensis Rev 1 and B. abortus
      B19 living anti-Brucella commercial vaccines obtained from six Spanish
      laboratories were tested in vitro and in vivo in the reference mouse model for
      quality control. All the strains tested showed the characteristic morphology of
      their respective Rev 1 or B19 reference strains with the exception of three Rev 1
      strains: seed lot SL2 and commercial vaccine R3, in which giant colonies were
      predominant, and commercial vaccine R5, in which 5% rough colonies were detected.
      Strains SL2 and R5 (but not the R3) had a deficient activity when tested in the
      mouse model. All strains but two (Rev 1 strain R1 and B19 strain B2) had standard
      resistance/ sensitivity patterns to streptomycin and penicillin G. Strains R1 and
      B2 had an increased resistance to penicillin when incubated in a 10% CO2
      atmosphere and both strains showed an increased residual virulence in mice. As
      residual virulence and immunogenicity in mice were not always correlated one
      another nor with the in vitro tests, all tests should be performed to control
      properly the anti-Brucella live vaccines. A computerized statistical procedure to
      calculate the residual virulence of vaccines is proposed as an alternative to
      that used in the current method.

PMID- 10885619
TI  - Measurement of plasma F2-isoprostanes as an index of lipid peroxidation does not
      appear to be confounded by diet.
AB  - F2-isoprostanes (F2-IPs) are formed by the free radical-catalysed oxidation of
      arachidonic acid. The measurement of F2-IPs, especially 8-epi-PGF2alpha, is
      recognised as a reliable marker of lipid peroxidation and is currently used as a
      sensitive index of oxidative stress in vivo. The majority of 8-epi-PGF2alpha
      present in the circulation occurs in association with lipoproteins which are
      synthesised in the liver. Since lipoproteins are derived from dietary fatty acids
      and triglycerides, it is possible that 8-epi-PGF2alpha generated in
      polyunsaturated fatty acid-rich food (during initial processing/packaging or
      during meal preparation) may become incorporated within these lipoproteins during
      synthesis. In view of the growing use of 8-epi-PGF2alpha as a marker of lipid
      peroxidation in vivo in nutritional or clinical studies, it is therefore
      important to investigate the possibility that the circulating levels measured
      could be confounded by the presence of 8-epi-PGF2alpha in food. In this study we
      evaluated the levels of 8-epi-PGF2alpha present in several popular fast-foods,
      using a combination of solid phase extraction and gas chromatography-mass
      spectrometry. Fast-foods were selected to represent meals prepared from vegetable
      , chicken-, fish- and meat-derived ingredients. Total (free + esterified) 8-epi
      PGF2alpha levels ranged from 0.09 to 0.73 pmol/g (122-644 pmol/mmol arachidonic
      acid), with the highest levels present in beef-derived meals. Further
      investigation of hamburgers and cheeseburgers revealed 8-epi-PGF2alpha levels of
      1.83 +/- 0.24 and 0.84 +/- 0.03nmol/mmol arachidonic acid, respectively. Lower
      concentrations of vitamin E were found in the hamburgers. The postprandial
      contribution to plasma 8-epi-PGF2alpha levels following ingestion of 100 g
      portions of these fast-foods would therefore be expected to be no greater than
      the low picomole range, and would be unlikely to influence the normal endogenous
      levels of 8-epi-PGF2alpha and those produced during oxidative stress.

PMID- 10885620
TI  - DNA strand scission by the nephrotoxin [2,2'-bipyridine]-3,3',4,4'-tetrol-1,1'
      dioxide and related compounds in the presence of iron.
AB  - The capacity of non-illuminated nephrotoxin orellanine ([2,2'-bipyridine]
      3,3',4,4'-tetrol-1,1'-dioxide) to induce DNA damage in the presence of ferrous
      iron and dioxygen has been evaluated. Maximal single-strand breaks in plasmid DNA
      were obtained with a metal to ligand ratio 1:3. Instantaneous oxidation of Fe2+
      in presence of orellanine under air was responsible for oxy-radical production
      concomitant to a stable ferric complex Fe(III)Or3 formation, leading to oxidative
      DNA breakage at physiological pH. DNA damage was lowered in the presence of SOD
      and catalase or DMSO, indicating a set of reactions that leads to oxy-radical
      generation. Iron chelators such as DTPA and EDTA had no protecting effect,
      Desferal slightly protected. GSH acted as an oxy-radical scavenger, whereas
      cysteine induced stronger damage. Closely related bipyridine compounds were also
      studied in presence of Fe2+ and O2 using a combination of spin-trapping and DNA
      nicking experiments, none of which were able to chelate iron and induce damage at
      pH 7. Both catecholic moieties and aminoxide groups are required for observing
      breakage at physiological pH.

PMID- 10885621
TI  - Oxidative stress after moderate to extensive burning in humans.
AB  - Lipid peroxidation products, lipid antioxidants, and hematologic and blood
      chemistry changes were evaluated in plasma of patients after acute burning injury
      involving 10% (n=8), 20% (n=8), and 40% (n=5) of total body surface area (TBSA),
      24 h after burning (baseline) up to 30 days after. Markedly increased plasma
      levels of malondialdehyde (MDA) were observed at baseline in all patients,
      according to the extent of the injury, then the values declined progressively.
      However, levels of MDA remained above normal up to 30 days even in less injured
      patients. On the other hand, the plasma level of conjugated diene lipid
      hydroperoxides was only slightly higher than control at the baseline, then
      dropped under the control value in all patients. Cholesterol showed a marked fall
      at baseline, followed by a rapidly progressive decrease, indicating a massive
      loss of circulating lipids by the acute thermal injury. Because of such an
      extensive and rapidly spreading oxidative degradation of lipids, decomposition of
      conjugated diene hydroperoxides, produced in early stages of the peroxidation
      process, occurs, so these compounds cannot be a suitable index to value lipid
      oxidation in burned patients. Aldehydic products of lipid peroxidation act as
      endotoxins, causing damage to various tissues and organs. Damage to liver and
      decrease of erythrocyte survival were assessed by increased plasma levels of
      asparate and alanine transaminases, within 7-15 days after injury, and by a
      decreased number of red blood cells, which remained under the normal value at 30
      days. A marked decrease of lipid antioxidants, beta-carotene, vitamin A and
      vitamin E was observed at baseline. The level of beta-carotene remained low in
      all patients at the end of the 30-day observation. A complete recovery of vitamin
      A did not occur at 30 days post-burn, even in the patients with 10% of burned
      TBSA. Plasma levels of vitamin E decreased significantly in 1-7 days after burn
      in all patients, but these levels increased thereafter, with almost total
      recovery at 30 days. These data show evidence of a marked, long-lasting
      oxidant/antioxidant imbalance in burned patients, in accordance with the severity
      of the injury, which is also reflected as systemic oxidant stress.

PMID- 10885622
TI  - Interactions of nitric oxide and oxygen in cytotoxicity: proliferation and
      antioxidant enzyme activities of endothelial cells in culture.
AB  - Nitric oxide (NO) shows cytotoxicity, and its reaction products with reactive
      oxygen species, such as peroxynitrite, are potentially more toxic. To examine the
      role of O2 in the NO toxicity, we have examined the proliferation of cultured
      human umbilical vein endothelial cells in the presence or absence of NO donor,
      ((Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-++ +ium-1,2-diolate)
      (DETA-NONOate) (100-500 microM), under normoxia (air), hypoxia (< 0.04% O2) or
      hyperoxia (88-94% O2). It was found that the dose dependency on NONOate was
      little affected by the ambient O2 concentration, showing no apparent synergism
      between the two treatments. We have also examined the effects of exogenous NO
      under normoxia and hyperoxia on the cellular activities of antioxidant enzymes
      involved in the H2O2 elimination, since many of them are known to be inhibited by
      NO or peroxynitrite in vitro. Under normoxia DETA-NONOate (500 microM) caused 25%
      decrease in catalase activity and 30% increases in glucose-6-phosphate
      dehydrogenase and 6-phosphogluconate dehydrogenase activities in 24h. Under
      hyperoxia NO caused about 25% decreases in activities of catalase, glutathione
      reductase and glucose-6-phosphate dehydrogenase. The H2O2 removal rate by NO
      treated cells was computed on the mathematical model for the enzyme system. It
      was concluded that the cellular antioxidant function is little affected by NO
      under normoxia but that it is partially impaired when the cells are exposed to NO
      under hyperoxia.

PMID- 10885623
TI  - Mitogen-activated protein kinase, ERK1/2, is essential for the induction of
      vascular endothelial growth factor by ionizing radiation mediated by activator
      protein-1 in human glioblastoma cells.
AB  - Vascular Endothelial Growth Factor (VEGF)/Vascular Permeability Factor plays an
      important role in angiogenesis and cell proliferation of cancer cells.
      Glioblastoma cells are most malignant and show resistance to radiation therapy
      inducing VEGF to cause angiogenesis and brain edema. In the present study, the
      regulatory mechanism of the expression of VEGF by ionizing radiation was studied
      in three human glioblastoma cells. Induction of VEGF mRNA by ionizing radiation
      was dependent on dose and incubation time. Activator protein-1 (AP-1) was
      activated by 10 Gy of ionizing radiation in 1 h in T98G glioblastoma cells on an
      electrophoretic mobility shift assay. We constructed chimeric genes containing
      various regions of the VEGF promoter gene and the coding region for
      chloramphenicol acetyltransferase (CAT) and transiently transfected them to T98G
      cells. CAT assay with the VEGF promoter gene containing an AP-1 site demonstrated
      that the promoter activity of the VEGF gene was enhanced by ionizing radiation.
      Immunological analysis of the activity of mitogen-activated protein kinase,
      ERK1/2, showed that this activity is up-regulated by ionizing radiation. These
      results suggest that ERK1/2 pathway is involved in the up-regulation of VEGF
      expression ionizing radiation mediated by AP-1, which may lead to further
      neovascularization and proliferation of glioblastoma cells resistant to radiation
      therapy.

PMID- 10885624
TI  - Measurement of oxidative stress in human liver by EPR spin-probe technique.
AB  - A method for the measurement of reactive oxygen species (ROS) in human hepatic
      tissue has been developed. The method is based on the EPR detection of the
      nitroxide radical produced by reaction of the hydroxylamine spin-probe bis(1
      hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate with ROS generated under
      pseudo-physiologic conditions in fine needle biopsies of healthy (10 controls)
      and diseased (22 patients) human liver. Measures of malonaldehyde in 9 liver
      biopsies (3 controls and 6 patients) have also been obtained by high pressure
      liquid chromatography and values parallel those obtained by the spin-probe
      technique. The amount of ROS found in healthy human liver (median = 1.8 x 10(-11)
      mol/mg) was significantly lower than values found in liver affected by hepatitis
      B (median=5.8 x 10(-10) mol/mg; p < 0.02) or by hepatitis C (median = 2.7 x 10(
      9) mol/mg; p < 0.003) as well as compared to some other non-viral liver diseases
      (NVLD): autoimmune hepatitis, primary biliary cirrhosis, primary schlerosing
      cholangitis (median = 9.8 x 10(-9) mol/mg; p < 0.005). NVLD also showed
      significantly higher ROS levels compared to hepatitis B (p < 0.04) and hepatitis
      C (p < 0.04). The mechanism, potentiality and limitations of our method are
      discussed.

PMID- 10885625
TI  - Increase in production of ascorbate radical in tissues of rat treated with
      paraquat.
AB  - The production of ascorbate radical (A*-) was investigated in tissues of rats
      intoxicated with paraquat (PQ) to know the protective role of antioxidant
      ascorbate (AH-) in tissues. The electron spin resonance (ESR) method is applied
      to observe A*-. To eliminate increased biosynthesis of ascorbic acid (AH2) by PQ
      intoxication, ODS rats were chosen and fed with or without 250 ppm PQ in the
      diet. The radical A*- was detected only in the lung and spleen homogenates of
      both intoxicated and control rats at the beginning of ESR measurement. The
      radical levels of intoxicated rat lung and spleen were increased rapidly to twice
      the initial level after 3 h and decreased to 0.2-0.6 times the initial level
      after 24 h, whereas those of control rats were increased slowly to 1.1 times the
      initial level after 4 h and decreased slowly to 0.7 times the initial level after
      24 h at 4 degrees C. In other organs such as liver, kidney, heart and testis, A*-
      was not detected initially but detected afterwards. Higher A*- level was observed
      in the intoxicated rat liver than the control but no appreciable differences of
      A*- levels were observed between the intoxicated kidney, heart and testis and the
      respective controls. In the intoxicated rat lung the concentration of AH2 is only
      half but that of A*- is twice as high as that of the control. Larger amounts of
      A*- produced in the intoxicated rats decayed more quickly than those in the
      control rats. The simple addition of PQ to the control organ enhanced neither A*-
      production nor A*- quenching. These facts suggest that the tissues damaged by PQ
      require larger amounts of AH- to detoxicate harmful oxidants, resulting in
      concomitant production of A*-.

PMID- 10885626
TI  - Inhibition of oxidative DNA damage in vitro by extracts of brussels sprouts.
AB  - Cruciferous vegetables have cancer preventive effects which may be due to
      reduction of oxidative DNA damage. We investigated the effect of an aqueous
      extract of cooked Brussels sprouts on formation of 7-hydro-8-oxo-2'
      deoxyguanosine (8-oxodG) in calf thymus DNA in vitro. Damage was induced by a
      Fenton reaction, UVC (254 nm), UVA (365 nm), sunlamp light, and methylene blue
      with visible light. The extract inhibited 8-oxodG formation in all systems except
      visible light with methylene blue. The IC50 values were 6-20 microg/ml
      corresponding to the extract of 5-20 g of Brussels sprouts distributed in a
      volume of 50 L. The protective effect in the Fenton reaction was unaffected by
      addition of EDTA. After HPLC separation fractions were identified with similar
      DNA protective effects. Sinigrin, a glucosinolate abundant in Brussels sprouts,
      co-eluted with the most effective fraction and had DNA protective effects. In
      comparison with other antioxidants the patterns of effect of the extract in the
      five damage systems were more similar to that of sodium azide than to those of
      dimethylsulfoxide and vitamin C. Constituents of Brussels sprouts can protect DNA
      by direct scavenging, e.g. hydroxyl radical and other oxidants, without
      prooxidant effects at concentrations potentially achievable by modest intake of
      the vegetable.

PMID- 10885627
TI  - The problem of obstetrical complications and schizophrenia.
AB  - The use of the term "obstetrical complications" (OCs) and its variations to
      encompass diverse physiological mechanisms (e.g., genetic, ischemic, hemorrhagic,
      infectious) of disruption to fetal/neonatal brain development has engendered
      inconsistency, confusion, and controversy. The principal reason is that the term
      OCs belies the absence of a fully adequate conceptual framework for
      characterizing neurodevelopmental risk. We propose that neurodevelopmental risk
      factors for schizophrenia can be assessed more clearly if broad OC scales are
      replaced by measures representing more homogeneous pathways of disturbed brain
      development. Using a new OC classification, we found that disordered growth
      related to hypoxic-ischemic compromise to early brain development may confer an
      elevated risk of schizophrenia and other adult-onset psychoses, particularly in
      the presence of familial risk. Abnormal fetal and neonatal brain growth and
      development in schizophrenia and OCs may also, at least in part, result from
      genetic factors and could help explain the relation between seemingly
      inconsistent OCs identified in prior research.

PMID- 10885628
TI  - U.S. birth cohort studies of schizophrenia: a sea change.

PMID- 10885629
TI  - The design of the prenatal determinants of schizophrenia study.
AB  - This paper describes the Prenatal Determinants of Schizophrenia (PDS) Study;
      three companion papers report the first results. The PDS Study was designed to
      study early antecedents of schizophrenia in a birth cohort of 1959-1967 for whom
      a wealth of archived prenatal data--including maternal sera--was available.
      Making use of the registries of a health plan into which the cohort was born, we
      ascertained and then diagnosed 71 cases of schizophrenia and spectrum disorders
      in the cohort. We describe herein the available prenatal data, the process of
      case diagnosis, and the strategies used to analyze prenatal determinants of
      schizophrenia in this cohort. Data are presented that bear on the main sources of
      potential bias and are important to understanding the strengths and limitations
      of this unique data set.

PMID- 10885630
TI  - Maternal prepregnant body mass and risk of schizophrenia in adult offspring.
AB  - This study examined the relation between maternal prepregnant body mass index
      (BMI) and development of schizophrenia and schizophrenia spectrum disorders in
      adult offspring from the Prenatal Determinants of Schizophrenia Study. The study
      drew on a previously studied cohort of births occurring between 1959 and 1967 to
      women enrolled in a prepaid health plan. Computerized treatment registries were
      used to identify possible cases of schizophrenia and spectrum disorders in adult
      offspring belonging to the health plan from 1981 to 1997. Diagnostic interviews
      and medical record reviews resulted in diagnosis of 63 cases of schizophrenia and
      spectrum disorders; these cases and 6,570 unrelated and unaffected cohort members
      whose mothers also had prepregnancy measures of BMI comprised the sample for
      analyses. High (> or = 30.0), compared with average (20.0-26.9), maternal
      prepregnant BMI (kg/m2) was significantly associated with schizophrenia and
      spectrum disorders in the adult offspring (relative risk [RR] = 2.9; 95%
      confidence interval [CI] 1.3-6.6), independently of maternal age, parity, race,
      education, or cigarette smoking during pregnancy. Low (< or = 19.9) maternal BMI
      was not associated with schizophrenia and spectrum disorders (RR = 1.2; 95% CI
      0.64-2.2). Future studies of this cohort will examine factors that may help
      explain the relationship of high maternal prepregnant BMI with schizophrenia,
      including nutritional and metabolic factors, toxic exposures, and obstetrical
      complications.

PMID- 10885631
TI  - Maternal exposure to respiratory infections and adult schizophrenia spectrum
      disorders: a prospective birth cohort study.
AB  - We sought to examine the relationship between maternal exposure to adult
      respiratory infections and schizophrenia spectrum disorder (SSD) in the Prenatal
      Determinants of Schizophrenia (PDS) Study, a large birth cohort investigation.
      Previous work suggests that second trimester exposure to respiratory infection
      may be a risk factor for SSD. We therefore examined whether this class of
      infection was associated with adult SSD. For this purpose, we capitalized on
      several design advantages of the PDS Study, including a comprehensive,
      prospective data base on physician-diagnosed infections and a continuous followup
      in which diagnoses of SSD were made, in the majority, by face-to-face interview.
      Second trimester exposure to respiratory infections was associated with a
      significantly increased risk of SSD, adjusting for maternal smoking, education,
      and race (rate ratio [RR] = 2.13 [1.05-4.35], chi2 = 4.36, df= 1,p = 0.04); no
      associations were shown for first trimester and third trimester exposure to these
      respiratory infections. These findings support-and extend-previous studies
      suggesting that second trimester respiratory infections are risk factors for SSD.
      This study therefore has implications toward uncovering the etiology of
      schizophrenia and developing preventive strategies.

PMID- 10885632
TI  - Incidence and cumulative risk of treated schizophrenia in the prenatal
      determinants of schizophrenia study.
AB  - The present study uses data from the Prenatal Determinants of Schizophrenia (PDS)
      Study to derive age- and sex-specific estimates of incidence and cumulative risk
      for DSM-IV schizophrenia. Although not designed as an incidence study, the PDS
      Study uses both a well-defined population under continuous followup and DSM-IV
      diagnoses. The originating cohort was established in Alameda County, California,
      during 1959-1967 and yielded 12,094 cohort members followed from 1981 to 1997
      during the principal ages at risk for schizophrenia. Survival analytic techniques
      showed that schizophrenia incidence rates per 10,000 person-years for men were
      9.4 for ages 15-19; 5.6 for ages 20-24; 3.3 for ages 25-29; and 0.9 for ages 30
      34. Schizophrenia incidence rates per 10,000 person-years for women were 1.6 for
      ages 15-19; 1.3 for ages 20-24; and 4.1 for ages 25-29. The cumulative risk for
      schizophrenia by age 38 was 0.93 percent for men and 0.35 percent for women.
      These estimates of incidence rates and risk were higher than those in traditional
      incidence studies but similar to recent findings in other cohorts. Possible
      explanations for the apparently high rates of disorder include chance, design
      effects, and true variation in risk over time and place.

PMID- 10885633
TI  - The relationship of prenatal and perinatal complications to cognitive functioning
      at age 7 in the New England Cohorts of the National Collaborative Perinatal
      Project.
AB  - Previous literature shows that children who later develop schizophrenia have
      elevated rates of prenatal and perinatal complications (PPCs) and
      neuropsychological deficits in childhood. However, little is known about the
      relationship of these risk factors to each other. We evaluated the relationship
      between PPCs and neuropsychological functioning at age 7 in a large
      epidemiological study of pregnancy, birth, and development: the National
      Collaborative Perinatal Project (NCPP). Thirteen standardized measures of
      cognitive abilities were acquired on 11,889 children at approximately age 7.
      Principal components analysis was used to create three neuropsychological
      measures: academic achievement skills, verbal-conceptual abilities, and
      perceptual-motor abilities. We measured the relationship between these factors
      and three measures of PPCs: low birth weight (LBW), probable hypoxicischemic
      complications, and chronic hypoxia. All three measures of PPCs were significantly
      associated with lower neuropsychological performance, after controlling for
      various confounders. LBW had the strongest association with neuropsychological
      performance, followed by an index of presumed hypoxic insults. The effect sizes
      between PPCs and cognitive factors at age 7 were consistently largest with
      perceptual-motor abilities, followed by academic achievement skills and verbal
      conceptual abilities. Future studies will evaluate the effects of specific PPCs
      and genetic risk factors for psychosis on cognitive functioning in childhood.

PMID- 10885634
TI  - Impact of genetic vulnerability and hypoxia on overall intelligence by age 7 in
      offspring at high risk for schizophrenia compared with affective psychoses.
AB  - Risk factors for schizophrenia, such as genetic vulnerability and obstetric
      complications, have been associated with cognitive deficits in schizophrenia. We
      tested the association of these risk factors with general intellectual ability in
      offspring at high risk for psychoses and normal control subjects. Offspring of
      182 parents with DSM-IV schizophrenia or affective psychoses were recruited and
      diagnosed from the Boston and Providence cohorts of the National Collaborative
      Perinatal Project (NCPP). Control subjects from the NCPP were selected to be
      comparable with affected parents based on the parent's age, ethnicity, study
      site, number of offspring enrolled in the NCPP, and payment status, and on the
      offspring's age, sex, and history of obstetric complications. Based on data
      prospectively acquired from pregnancy and events of gestation, labor, delivery,
      and the neonatal period, we derived a measure of probable hypoxic-ischemic
      insult. We also report on standardized measures of general intelligence
      (intelligence quotient [IQ]) collected at age 7. General linear mixed models were
      used to test for the simultaneous effects of genetic vulnerability, defined as
      parental diagnosis, and probable hypoxic insult on age 7 IQ. Specificity of the
      effects for schizophrenia compared with affective psychoses and sex effects were
      also tested. Low IQ at age 7 was significantly associated with genetic
      vulnerability to psychoses, in particular with schizophrenia.

PMID- 10885635
TI  - Maternal recall of pregnancy history: accuracy and bias in schizophrenia
      research.
AB  - Most investigations that report a positive association between obstetric
      complications and schizophrenia have been case-control studies that are often
      based on long-term maternal recall of events during pregnancy. We tested the
      hypothesis that mothers of adult offspring with schizophrenia or other psychoses
      systematically overreport obstetric complications compared with mothers of
      unaffected offspring. Subjects were selected from the New England cohorts of the
      National Collaborative Perinatal Project, a large prospective cohort with well
      documented records of pregnancy and delivery. Mothers of 39 offspring with
      psychosis and 39 control offspring were recontacted and completed a structured
      interview regarding their pregnancy history. Accuracy of maternal recall varied
      greatly in relation to the type of pregnancy event, and recall was inaccurate for
      many specific events. For the control sample only, maternal recall of the total
      number of complications corresponded closely to chart information. Contrary to
      the study hypothesis, mothers of offspring with psychosis report fewer
      complications than indicated in their obstetric records, with no evidence of
      positive recall bias. These results suggest that previous reports of a positive
      association between obstetric complications and schizophrenia are not likely to
      have resulted from biased maternal recall.

PMID- 10885636
TI  - A prospective cohort study of genetic and perinatal influences in the etiology of
      schizophrenia.
AB  - In this study, we examined whether fetal hypoxia and other obstetric
      complications (OCs) are related to risk for adult schizophrenia; whether such
      effects are specific to cases with an early age at onset; and whether the
      obstetric influences depend on, covary with, or are independent of familial risk.
      Subjects were 72 patients with schizophrenia or schizoaffective disorder; 63 of
      their siblings not diagnosed with schizophrenia; and 7,941 nonpsychiatric
      controls, whose gestations and births were monitored prospectively with standard
      research protocols as part of the National Collaborative Perinatal Project. Adult
      psychiatric morbidity was ascertained via a longitudinal treatment data base
      indexing regional public health service utilization, and diagnoses were made by
      review of all pertinent medical records according to DSM-IV criteria. We found
      that the odds of schizophrenia increased linearly with increasing number of
      hypoxia-associated OCs and that this effect was specific to cases with an early
      age at onset/first treatment contact. There were no relationships between
      schizophrenia and birth weight or other (prenatal/nonhypoxic) OCs. Siblings of
      patients with schizophrenia were no more likely to have suffered hypoxia
      associated OCs than were nonpsychiatric cohort controls. Because the majority of
      individuals exposed to fetal hypoxia did not develop schizophrenia, such factors
      likely are incapable of causing schizophrenia on their own. Together, these
      findings suggest that hypoxia acts additively or interactively with genetic
      factors in influencing liability to schizophrenia. We propose a model in which
      the neurotoxic effects of fetal hypoxia may lead to an earlier onset of psychosis
      because of premature pruning of cortical synapses.

PMID- 10885637
TI  - Childhood neuromotor dysfunction in schizophrenia patients and their unaffected
      siblings: a prospective cohort study.
AB  - Neuromotor dysfunction is a consistent finding in high-risk and archival studies
      of schizophrenia, but the sources of this dysfunction and its role in the
      developmental course of the disorder remain poorly understood. This study
      examined childhood motor predictors of adult psychiatric outcome in a birth
      cohort sample (72 patients with schizophrenia or schizoaffective disorder, 63
      unaffected siblings, and 7,941 nonpsychiatric controls), evaluated prospectively
      with neurologic examinations at 8 months, 4 years, and 7 years of age. Deviance
      on motor coordination measures at 7 years was associated with both adult
      schizophrenia and unaffected sibling status, suggesting that a cofamilial (and
      perhaps genetic) factor underlies motor coordination deficits in schizophrenia.
      Unusual movements at ages 4 and 7 predicted adult schizophrenia but not
      unaffected sibling status, indicating that these deficits may be specific to
      those who will develop the clinical phenotype. None of the motor precursors were
      confined to patients with an early age at first treatment contact. Fetal hypoxia
      predicted unusual movements at 4 but not 7 years among the preschizophrenia
      subjects, suggesting neurodevelopmental dependence of its functional effects.
      Neither prenatal complications nor birth weight were associated with motor
      dysfunction in preschizophrenia subjects or their unaffected siblings at any age.
      Finally, preschizophrenia children did not show the expected developmental
      decline in unusual movements, perhaps reflecting aberrant functional maturation
      of cortical-subcortical pathways.

PMID- 10885638
TI  - Childhood cognitive functioning in schizophrenia patients and their unaffected
      siblings: a prospective cohort study.
AB  - While it is known that children of schizophrenia parents perform more poorly on
      tests of cognitive functioning than children of normal parents, less certain is
      the degree to which such deficits predict schizophrenia outcome, whether
      cognitive functioning deteriorates during childhood in preschizophrenia
      individuals, and whether nongenetic etiologic factors (such as obstetric
      complications) contribute to these deficits. In the present study, 72 patients
      with schizophrenia or schizoaffective disorder, 63 of their siblings not
      diagnosed with schizophrenia, and 7,941 controls with no diagnosis were
      ascertained from a birth cohort whose members had been evaluated with
      standardized tests of cognitive functioning at 4 and 7 years of age. Adult
      psychiatric morbidity was ascertained via a longitudinal treatment data base
      indexing regional public health service utilization, and diagnoses were made by
      review of all pertinent medical records according to DSM-IV criteria. Both the
      patients with schizophrenia and their unaffected siblings performed significantly
      worse than the nonpsychiatric controls (but did not differ from each other) on
      verbal and nonverbal cognitive tests at 4 and 7 years of age. Preschizophrenia
      cases and their siblings were increasingly overrepresented across decreasing
      quartiles of the performance distributions. There was not significant intra
      individual decline, and there were no significant relationships between obstetric
      complications and test performance among the preschizophrenia subjects. These
      results suggest that during the period from age 4 to age 7 years, premorbid
      cognitive dysfunction in schizophrenia represents a relatively stable indicator
      of vulnerability deriving from primarily genetic (and/or shared environmental)
      etiologic influences.

PMID- 10885639
TI  - A prospective cohort study of childhood behavioral deviance and language
      abnormalities as predictors of adult schizophrenia.
AB  - Language and behavioral deviance in early childhood in preschizophrenia
      individuals suggests that the pathologic processes predisposing to schizophrenia
      are present from early in life. However, the etiologic antecedents of such
      impairments, and the degree to which they predict adult schizophrenia, have not
      been conclusively demonstrated. To address this, we examined language and
      behavioral predictors of adult psychiatric outcome in a population cohort (72
      individuals with schizophrenia or schizoaffective disorder, 63 of their
      unaffected siblings, and 7,941 with no diagnosis) evaluated prospectively with
      behavioral examinations and a speech and language evaluation at 8 months, 4
      years, and 7 years of age. Psychiatric outcome was ascertained via adult
      treatment contacts, and diagnoses were made by chart review according to DSM-IV
      criteria. Social maladjustment at age 7 was found to predict adult schizophrenia,
      and focal deviant behaviors (e.g., echolalia, meaningless laughter) at ages 4 and
      7 were significantly associated with both schizophrenia and sibling status.
      Unintelligible speech at age 7 was a highly significant predictor of adult
      schizophrenia (odds ratio = 12.7), and poor expressive language ability predicted
      both schizophrenia and unaffected sibling outcome. Early behavioral and language
      dysfunction did not differentially characterize preschizophrenia subjects with a
      history of fetal hypoxia or an early age of first treatment contact. Given that
      unaffected siblings show similar signs of deviance, such problems may indicate
      genotypic susceptibility to the disorder, or shared environmental influences, or
      both.

PMID- 10885640
TI  - Schizophrenia research: a progress report, summarizing proceedings of the 1999
      International Congress on Schizophrenia Research.
AB  - The Seventh International Congress on Schizophrenia Research was held in Santa
      Fe, New Mexico, in April 1999. This was the largest Congress meeting to date,
      with almost 1,000 presentations that covered all aspects of schizophrenia
      research. This article provides an account of the Congress proceedings. Several
      research areas received extensive coverage, including early detection of illness
      through the use of cognitive and behavioral precursors of schizophrenia and the
      etiology and treatment of childhood-onset and first episode schizophrenia. The
      etiopathophysiological hypothesis of schizophrenia as a disorder of neural
      dysconnectivity was promoted across cognitive, neurochemical, neuroimaging, and
      postmortem domains. The importance of cognition as a major outcome measure and
      the impact of new antipsychotics on the treatment and conceptualization of
      schizophrenia were also major topics. Overall, the conference was noteworthy for
      the convergence of findings across research domains.

PMID- 10885641
TI  - Clozapine augmentation: safety and efficacy.
AB  - While clozapine has been demonstrated to be efficacious in refractory
      schizophrenia and possibly schizoaffective as well as bipolar disorders, a
      substantial number of patients still remain unresponsive. One strategy in
      treating these refractory patients is to augment clozapine with other somatic
      treatments. This article reviews the efficacy and safety of the combination of
      clozapine with other somatic treatments. A total of 70 articles were obtained
      from a manual, as well as computerized (Medline), search of the English language
      literature from 1978 to March 1998. Few controlled studies exist; most were case
      reports/series. From these data, the greatest risk of adverse effects seems to be
      associated with clozapine combined with benzodiazepines, valproate, or lithium,
      but no currently evaluated combination is absolutely unsafe. In terms of
      efficacy, the data suggest a number of potential augmentation strategies,
      although controlled data are few. Combination therapies with clozapine are common
      in clinical practice, despite a lack of empirical data, and the benefits and
      risks of these combinations need to be systematically reviewed.

PMID- 10885642
TI  - The effects of clozapine on alcohol and drug use disorders among patients with
      schizophrenia.
AB  - Several case studies indicate that clozapine use is associated with reductions in
      the use of nicotine, alcohol, or illicit drugs. Although not designed to assess
      clozapine, this study explored a posteriori the effects of clozapine on alcohol
      and drug use disorders among schizophrenia patients. Among 151 patients with
      schizophrenia or schizoaffective disorder and co-occurring substance use disorder
      who were studied in a dual-disorder treatment program, 36 received clozapine
      during the study for standard clinical indications. All participants were
      assessed prospectively at baseline and every 6 months over 3 years for
      psychiatric symptoms and substance use. Alcohol-abusing patients taking clozapine
      experienced significant reductions in severity of alcohol abuse and days of
      alcohol use while on clozapine. For example, they averaged 54.1 drinking days
      during 6-month intervals while off clozapine and 12.5 drinking days while on
      clozapine. They also improved more than patients who did not receive clozapine.
      At the end of the study, 79.0 percent of the patients on clozapine were in
      remission from alcohol use disorder for 6 months or longer, while only 33.7
      percent of those not taking clozapine were remitted. Findings related to other
      drugs in relation to clozapine were also positive but less clear because of the
      small number of patients with drug use disorders. This study was limited by the
      naturalistic design and the lack of prospective, standardized measures of
      clozapine use. The use of clozapine by patients with co-occurring substance
      disorders deserves further study in randomized clinical trials.

PMID- 10885643
TI  - Recent patterns and predictors of antipsychotic medication regimens used to treat
      schizophrenia and other psychotic disorders.
AB  - Up-to-date data are needed on the types of treatments used by psychiatrists and
      the reasons for use of particular treatments. Using 1997 American Psychiatric
      Association (APA) Practice Research Network (PRN) Study data on patients with
      schizophrenia and other psychotic disorders, we identified the characteristics of
      antipsychotic medications (APMs) currently being prescribed and factors
      associated with the use of particular regimens. In this study population, use of
      the newer APMs, including risperidone, olanzapine, and clozapine, has increased
      rapidly and now accounts for over one-half of all APM use. Other intriguing
      findings include the fact that one-sixth of patients with schizophrenia and other
      psychotic disorders are concurrently treated with two or more APMs. Factors
      associated with being prescribed one of the newer APMs risperidone or olanzapine
      include being elderly, having more education, being white, having psychiatric
      comorbidity, and making fewer recent visits to a psychiatrist. The APA PRN Study
      data are an important new resource for mental health services researchers.

PMID- 10885644
TI  - Genetic and state variables of neurocognitive dysfunction in schizophrenia: a
      twin study.
AB  - To characterize the familiality of cognitive dysfunction in schizophrenia, we
      studied performance on three tasks (visuospatial attention; visuolinguistic
      conflict, arrow-word; and Wisconsin Card Sorting Test [WCST]) by monozygotic (MZ)
      and dizygotic (DZ) twin pairs discordant for schizophrenia. The subject sample
      consisted of six MZ twin pairs, nine DZ twin pairs, and one MZ and one DZ
      nonschizophrenia cotwin of a patient with schizophrenia. There were two sources
      of cognitive dysfunction: a nonheritable, state component and a heritable, trait
      component. Deficits surfaced during the WCST in nonschizophrenia MZ cotwins; this
      impairment resolved following training in nonschizophrenia MZ cotwins, but not in
      the probands with schizophrenia, who performed abnormally in all tasks. The
      results suggest that nonheritable protective factors modulate the specific,
      plastic, and sometimes subtle neurocognitive deficits related to the
      schizophrenia genotype.

PMID- 10885645
TI  - Simple schizophrenia revisited: a clinical, neuropsychological, and neuroimaging
      analysis of nine cases.
AB  - Simple schizophrenia is widely considered to be a controversial or even
      discredited entity. However, cases showing typical clinical features continue to
      be identified in surveys of schizophrenia patients. This article reports on nine
      patients who met proposed diagnostic criteria for simple schizophrenia. The
      patients all showed the classical features of social and occupational decline, as
      well as negative symptoms in the absence of clear-cut positive symptoms. A range
      of other symptoms, which were either nonspecific or fell short of psychotic
      phenomena, was also seen. Neuropsychological testing revealed evidence of general
      intellectual impairment plus deficits in executive function and memory. Computed
      tomography scans were normal or showed only minor abnormalities. All patients,
      however, showed abnormalities on single photon emission computerized tomography
      (SPECT), mainly affecting frontal and temporal regions. It is concluded that
      cases conforming to the original descriptions of simple schizophrenia continue to
      be seen and are still best understood as representing a form of schizophrenia.

PMID- 10885646
TI  - Is anhedonia a specific dimension in chronic schizophrenia?
AB  - This article explores the relationships among anhedonia, depression, and
      schizophrenic symptomatology in chronic schizophrenia. To explore these
      relationships, factor analysis methods were used to analyze the latent
      organization of the variables. The Fawcett Clark Pleasure Capacity Scale-Physical
      Pleasure (FCPCS-PP) and the abridged version of the Beck Depression Inventory
      (BDI) were completed by 150 subjects who met research diagnostic criteria for
      definite chronic schizophrenia. The schizophrenic symptomatology was rated using
      the Positive and Negative Syndrome Scale (PANSS). Two separate exploratory
      principal components analyses were completed, followed by varimax rotation. The
      first was made on the correlation matrix comprising items from both the FCPCS-PP
      and PANSS and yielded a five-factor solution with virtually no overlap of the
      significant factor loadings for the items from each scale. The second was made on
      the correlation matrix comprising items from both the FCPCS-PP and BDI and
      yielded a two-factor solution with virtually no overlap of the significant factor
      loadings for the items from each scale. Confirmatory factor analyses
      corresponding to the two exploratory factor analyses were done to examine the
      goodness of fit of the five-factor solution versus a four-factor solution and the
      two-factor solution versus a one-factor solution. The five-factor and the two
      factor solutions yielded the best fit to the data relative to the other models
      tested. The findings support the view that part of anhedonia is a construct that
      is distinct and separate from depression and schizophrenic symptomatology in
      chronic schizophrenia.

PMID- 10885647
TI  - First person account: falling on the pavement.

PMID- 10885648
TI  - Operative obstetrics: a lost art?

PMID- 10885649
TI  - Pessaries for the treatment of incompetent cervix and premature delivery.
AB  - The purpose of this study was to review published articles about using pessaries
      in women with an incompetent cervix or who are at risk for preterm delivery. A
      MEDLINE search was performed from 1966 to 2000, with articles published before
      1966 being extracted from the reference lists of articles obtained. Foreign
      articles were translated into English. Key words included pessary, incompetent
      cervix, and preterm labor. All studies that included patient data were included.
      A variety of studies suggest that pessaries can increase the percentage of full
      term deliveries when used in women with an incompetent cervix or at risk for
      preterm delivery. When looking at women thought to have an incompetent cervix,
      the studies are mostly old case series. One prospective, randomized trial
      demonstrated no difference between women treated with a pessary and a cerclage.
      However, 27 weeks was the average gestational age at which therapy was started.
      In women at risk for preterm delivery, retrospective studies show an increase in
      full-term pregnancy rates with pessary use. One prospective, nonrandomized study
      also shows an increase in full-term pregnancy rate. However, in this study, lower
      risk patients received the pessary. Because of the poor nature of most of the
      studies, pessaries should not replace cerclage use at this time in women with an
      incompetent cervix. However, pessary use should be considered as adjuncts to
      cerclage or in women who are not candidates for cerclage. Also, pessary use may
      be considered in some women at risk for preterm delivery. Randomized perspective
      controlled trials are in progress to address the use of pessaries in these
      situations. Vaginal pessaries have been reported to be useful in women at risk
      for preterm delivery since 1959. Bedrest and cervical cerclage has become
      standard therapy in the United States for women with an incompetent cervix.
      However, cerclage is not without risk. Furthermore, advances in ultrasound have
      allowed us to identify women potentially at risk for preterm delivery by
      detecting cervical shortening before dilatation. This ability has raised
      questions concerning how to manage patients with subtle ultrasound changes. This
      article reviews the published literature concerning the use of pessaries in women
      with an incompetent cervix or at risk for early delivery.

PMID- 10885650
TI  - Ontogeny: the evolution of an oocyte.
AB  - The physiology of oocyte development, maturation, and selection forms the basis
      for understanding ovarian follicle dynamics, reproductive function and ovulation
      induction. The number of ovarian follicles with which women are invested from
      birth and the rate of decline determine their reproductive lifespan. The
      processes of atresia and apoptosis constantly deplete this finite store. The
      initiation of follicle growth involves complex chemical signaling and ensures
      that a cohort of follicles is prepared for recruitment monthly. The effects of
      gonadotrophins, autocrine signals, and the degree of vascularization further
      determine dominance and the selection of an oocyte for ovulation.

PMID- 10885651
TI  - Review of vaginal pessaries.
AB  - Pessaries have been used to treat pelvic organ prolapse throughout history,
      although with advances in the field of anesthesia and in surgical technique
      during the past century, pessary use declined. Current indications for pessary
      use include women awaiting definitive surgical repair, treatment for an
      unsuccessful surgical repair, treatment for women who are not surgical
      candidates, and for those who prefer medical management. In addition pessary use
      is gaining popularity among women with stress urinary incontinence, as well as in
      younger women interested in maintaining child bearing capabilities. Neonatal
      pelvic organ prolapse has also been treated successfully with pessaries. Many
      physicians have limited experience with pessary selection and fitting. This
      review article attempts to provide a basic overview of pessary selection and
      management.

PMID- 10885652
TI  - Differentiation and histological analysis of embryonic stem cell-derived neural
      transplants in mice.
AB  - We report here that neural transplantation of in vitro-differentiated embryonic
      stem (ES) cells provides a versatile strategy for gene transfer into the central
      nervous system. ES cells were subjected to an optimized in vitro differentiation
      protocol to obtain embryoid bodies. These aggregates were stereotaxically
      transplanted into the brain of recipient adult mice, where they followed a
      strictly controlled differentiation pattern and eventually formed mature neural
      grafts. A marker gene, introduced into the ROSA26 locus allowed for precise
      determination of the fate of the descendants of the transplanted embryoid bodies
      and revealed that not only neurons but also astrocytes, oligodendrocytes and even
      microglial cells were graft-derived. Evaluation of long-term experiments showed
      viable grafts with a stable transgene expression and proved that this approach
      provides a tool for reliable gene expression within a spatially delimited area of
      neural tissue.

PMID- 10885653
TI  - Astroblastoma: clinicopathologic features and chromosomal abnormalities defined
      by comparative genomic hybridization.
AB  - Astroblastomas are uncommon brain tumors whose classification and histogenesis
      have been debated. Precise criteria for diagnosis have been described only
      recently, but have not found wide acceptance. We report the clinical,
      radiographic, and histopathologic features of 20 astroblastomas, and the
      chromosomal alterations in seven cases as detected by comparative genomic
      hybridization (CGH). The tumors occurred both in children and young adults
      (average age, 14 years), most often as well circumscribed, peripheral, cerebral
      hemispheric masses. Radiographically, the lesions were contrast-enhancing and
      solid, often with a cystic component. All were characterized histologically by
      astroblastic pseudorosettes, and most displayed prominent perivascular
      hyalinization, regional hyaline changes, and pushing borders in regard to
      adjacent brain. Tumor cells were strongly immunoreactive for S-100 protein, GFAP,
      and vimentin. Staining for EMA was focal. Ten of 20 astroblastomas were
      classified as "well differentiated" and 10 were classified as "malignant,"
      largely on the basis of hypercellular zones with increased mitotic indices,
      vascular proliferation, and necrosis with pseudopalisading. All 10 well
      differentiated lesions and 8 of 10 malignant lesions were completely resected.
      None of the well differentiated astroblastomas recurred within the limited follow
      up period. Three malignant astroblastomas recurred, including two incompletely
      resected tumors, and one that had been totally resected. One patient died of
      disease following recurrence. The most frequent chromosomal alterations detected
      by CGH were gains of chromosome arm 20q (4/7 tumors) and chromosome 19 (3/7). The
      combination of these gains occurred in three, including two well differentiated
      and one malignant astroblastoma. Other alterations noted in two tumors each were
      losses on 9q, 10, and X. These chromosomal alterations are not typical of
      ependymoma or infiltrating astrocytic neoplasms, and suggest that astroblastomas
      may have a characteristic cytogenetic profile in addition to their distinctive
      clinical, radiographic, and histopathologic features.

PMID- 10885654
TI  - Neuronal FasL induces cell death of encephalitogenic T lymphocytes.
AB  - Apoptosis of inflammatory cells plays a crucial role in the recovery from
      autoimmune CNS disease. However, the underlying mechanisms of apoptosis induction
      are as yet ill-defined. Here we report on the neuronal expression of FasL and its
      potential function in inducing T-cell apoptosis. Using a combination of facial
      nerve axotomy and passive transfer encephalomyelitis, the fate of CD4+
      encephalitogenic T cells engineered to express the gene for green fluorescent
      protein was followed. FasL gene transcripts and FasL protein were detected in
      neurons by in sit-hybridization and immunohistochemistry. T cells infiltrating
      preferentially the injured brain parenchyma were found in the immediate vicinity
      of FasL expressing neurons and even inside their perikarya. In contrast to
      neurons, T cells rapidly underwent apoptosis. In co-cultures of hippocampal nerve
      cells and CD4 T lymphocytes, we confirmed expression of FasL in neurons and
      concomitant induction of T-cell death. Antibodies blocking neuronal FasL were
      shown to have a protective effect on T-cell survival. Thus, FasL expression by
      neurons in neuroinflammatory diseases may constitute a pivotal mechanism
      underlying apoptosis of encephalitogenic T cells.

PMID- 10885655
TI  - Axonal damage induced by invading T cells in organotypic central nervous system
      tissue in vitro: involvement of microglial cells.
AB  - Neuroinflammation in the course of multiple sclerosis and experimental autoimmune
      encephalomyelitis results in demyelination and, recently demonstrated, axonal
      loss. Invading neuroantigen specific T cells are the crucial cellular elements in
      these processes. Here we demonstrate that invasion of activated T cells induces a
      massive microglial attack on myelinated axons in entorhinal-hippocampal slice
      cultures. Flow cytometry analysis of activation markers revealed that the
      activation state of invading MBP-specific T cells was significantly lower in
      comparison to PMA-activated T cells. Moreover, MBP-specific T cells showed a
      significantly lower secretion of IFN-gamma. Conversely, MBP-specific T cells
      displayed a significantly higher potential to trigger activation of microglial
      cells, i.e. upregulation of MHC class II and ICAM-1 expression, and, most
      importantly, microglial phagocytosis of pre-traced axons. Our data suggest that
      this was mediated via specific cellular interactions of T cells and microglial
      cells since IFN-gamma alone was not sufficient to induce axonal damage while such
      damage was apparent in response to TNF-alpha which is released by activated
      microglial cells. TNF-alpha secretion by both T cell populations was negligible.
      Thus, MBP-specific T cells which invade nervous tissue in the course of
      neuroinflammation are more effective in axon-damaging recruiting microglial cells
      than activated T cells of other specificities.

PMID- 10885656
TI  - Lewy bodies in Alzheimer's disease: a neuropathological review of 145 cases using
      alpha-synuclein immunohistochemistry.
AB  - Antibodies to alpha-synuclein (AS) now provide a sensitive and specific method
      for the detection of Lewy bodies (LBs) and their use will allow a more accurate
      determination of the prevalence of LBs in Alzheimer's Disease (AD). Studies using
      AS immunohistochemistry (IHC) have found LBs in the amygdala of over 60% early
      onset familial AD and in 50% of Down's syndrome patients with AD, however, no
      studies have reported the use of AS IHC to detect LBs in a large cohort of
      sporadic AD. This study examined 145 sporadic AD cases diagnosed using CERAD
      criteria from 1995-1999 for the presence of LBs using AS IHC. AS IHC detected LBs
      in 88/145 (60.7%) of sporadic AD cases. Similarly, LBs were found in 56.8% of the
      95 cases fulfilling the more stringent NIA-RI criteria for the diagnosis of AD
      (Braak stage 5-6). In all cases with LBs, the amygdala was involved and LBs were
      always most numerous in this area, however, in some cases LBs in the substantia
      nigra were rare or not present. In conclusion, this study found that AS IHC
      detects LBs in the majority of sporadic AD cases and that the amygdala is the
      most commonly affected region.

PMID- 10885657
TI  - Expression analysis of ataxin-7 mRNA and protein in human brain: evidence for a
      widespread distribution and focal protein accumulation.
AB  - Spinocerebellar ataxia 7 (SCA7) is an autosomal dominant neurodegenerative
      disorder caused by the expansion of a CAG-trinucleotide repeat in the coding
      region of the SCA7 gene. The expansion is translated into an extended
      polyglutamine stretch in the protein ataxin-7, a protein of unknown function. By
      Northern blot analysis expression of ataxin-7 was detected in numerous regions of
      human brain and some peripheral tissues. It is unknown, however, if ataxin-7 is
      enriched at sites of the SCA7 pathology. We studied the regional and cellular
      expression pattern of ataxin-7 at the mRNA level by in situ hybridization
      histochemistry in normal human brain. Furthermore we used a monoclonal and two
      polyclonal antibodies raised against the normal ataxin-7 to establish the
      distribution of this protein in brain, retina and peripheral organs. At the mRNA
      level ataxin-7 was preferentially expressed in neurons; the regional distribution
      reflected neuronal packing density. Ataxin-7 immunoreactivity (IR) was similarly
      widely expressed. In most neurons, ataxin-7 IR was preferentially localized to
      the cytoplasmatic compartment although some nuclear ataxin-7 IR was detected in
      most neurons. A more intense and more prominently nuclear ataxin-7 IR was
      observed in neurons of the pons and the inferior olive, brain regions severly
      affected by the disease, suggesting that the subcellular localization and
      abundance of ataxin-7 is regulated in a regionally specific way. Since neurons
      displaying more intense and more prominently nuclear ataxin-7 IR belonged to the
      class of susceptible cells in SCA7, an enrichment of normal ataxin-7 in the
      nuclear compartment may contribute to neurodegeneration. However not all sites of
      SCA7 pathology displayed a strong cytoplasmatic and nuclear immunoreactivity.

PMID- 10885658
TI  - Chromosomal imbalances in brain metastases of solid tumors.
AB  - Metastases account for approximately 50% of the malignant tumors in the brain. In
      order to identify structural alterations that are associated with tumor
      dissemination into the central nervous system we used Comparative Genomic
      Hybridization (CGH) to investigate 42 brain metastases and 3 primary tumors of 40
      patients. The metastases originated from lung cancer (14 cases), melanomas (7),
      carcinomas of breast (5), colon (5), kidney (5), adrenal gland (1) and thyroid
      (1). In addition, tumors of initially unknown primaries were assessed in 3 cases.
      The highest incidence of DNA gains were observed for the chromosomal regions
      1q23, 8q24, 17q24-q25, 20q13 (>80% of cases) followed by the gain on 7p12 (77%).
      DNA losses were slightly less frequent with 4q22, 4q26, 5q21, 9p21 being affected
      in at least 70% of the cases followed by deletions at 17p12, 4q32q34, 10q21,
      10q23-q24 and 18q21-q22 in 67.5% of cases. Two unusual narrow regional peaks were
      observed for the gain on 17q24-q25 and loss on 17p12. The incidence at individual
      loci can be viewed at our CGH online tumor database at http://
      amba.charite.de/cgh/. The metastases of each tumor type showed a recurrent
      pattern of changes. In those cases with primary tumor and metastases available,
      the CGH pattern exhibited a high degree of conformity. In conclusion, our data
      suggests that specific genetic lesions are associated with tumor dissemination
      into the nervous system and that CGH analysis may be a useful supplementary tool
      for classification of metastases with unknown origin.

PMID- 10885659
TI  - Antibody association with a novel model for primary progressive multiple
      sclerosis: induction of relapsing-remitting and progressive forms of EAE in H2s
      mouse strains.
AB  - Multiple sclerosis (MS) can be divided into 4 clinical forms: relapsing-remitting
      (RR), primary progressive (PP), secondary progressive (SP), and progressive
      relapsing (PR). Since PP-MS is notably different from the other forms of MS, both
      clinically and pathologically, the question arises whether PP-MS is
      immunologically similar to the other forms. The pathogenesis of the PP-MS remains
      unclear, partly due to a lack of highly relevant animal models. Using an
      encephalitogenic peptide from myelin oligodendrocyte glycoprotein (MOG)92-106, we
      have established animal models that mimic different forms of MS in 2 strains of H
      2s mice, SJL/J and A.SW. We induced experimental allergic encephalomyelitis (EAE)
      using MOG92-106 in the presence or absence of supplemental Bordetella pertussis
      (BP). Although, SJL/J mice developed RR-EAE whether BP was given or not, A.SW
      mice developed PP-EAE without BP and SP-EAE with BP. Histologically, SJL/J mice
      developed mild demyelinating disease with T cell infiltration, while A.SW mice
      developed large areas of plaque-like demyelination with immunoglobulin deposition
      and neutrophil infiltration, but with minimal T cell infiltration. In A.SW mice
      without BP, high titer serum anti-MOG antibody was detected and the anti-MOG
      IgG2a/IgG1 ratio correlated with survival times of mice. We hypothesized that, in
      A.SW mice, a Th2 response favors production of myelinotoxic antibodies, leading
      to progressive forms with early death. Our new models indicate that a single
      encephalitogen could induce either RR-, PP-, or SP- forms of demyelinating
      disease in hosts with immunologically different humoral immune responses.

PMID- 10885660
TI  - Introduction: mitochondrial encephalomyopathies.

PMID- 10885661
TI  - Neuropathologic aspects of cytochrome C oxidase deficiency.
AB  - Cytochrome c oxidase (COX) deficiency is an important cause of myopathy or
      encephalomyopathy. Considering the structural complexity of COX, its dual genetic
      control, and the several nuclear genes needed for its proper assembly, the
      phenotypic heterogeneity is not surprising. From a morphologic view point, the
      application of histochemistry and immunohistochemistry to the study of COX
      deficiency in muscle has revealed specific patterns that -we believe- are helpful
      both for diagnosis and for directing sequencing studies of either mitochondrial
      DNA (mtDNA) or nuclear DNA (nDNA) genes. Similar studies in brain have shown that
      patients with mutations in mtDNA appear to have different patterns of COX
      deficiency from patients with mutations in nDNA genes. The recent discovery of
      mutations in COX assembly genes coupled with the potential to generate knock-out
      mice with these mutations holds the promise of providing the neuropathologist
      with the animal models needed to study the pathogenesis of COX deficiency in
      brain and muscle.

PMID- 10885662
TI  - Mutations in mtDNA: are we scraping the bottom of the barrel?
AB  - The small, maternally inherited mtDNA has turned out to be a Pandora's box of
      pathogenic mutations: 12 years into the era of "mitochondrial medicine," about
      100 pathogenic point mutations and innumerable rearrangements have been
      associated with a bewildering variety of multisystemic as well as tissue-specific
      human diseases. After reviewing the principles of mitochondrial genetics, we
      compare and contrast the clinical and pathological features of disorders due to
      mutations in genes affecting mitochondrial protein synthesis with those of
      mutations in protein-coding genes. In contrast to the striking progress in our
      understanding of etiology, pathogenesis is only partially explained by the rules
      of mitochondrial genetics and remains largely terra incognita. We review recent
      progress in prenatal diagnosis and epidemiology. Therapy is still woefully
      inadequate, but a number of promising approaches are being developed.

PMID- 10885663
TI  - Mitochondrial respiratory chain diseases and mutations in nuclear DNA: a
      promising start?

PMID- 10885664
TI  - Defects of intergenomic communication: where do we stand?
AB  - An expanding number of autosomal diseases has been associated with mitochondrial
      DNA (mtDNA) depletion and multiple deletions. These disorders have been
      classified as defects of intergenomic communication because mutations of the
      nuclear DNA are thought to disrupt the normal cross-talk that regulates the
      integrity and quantity of mtDNA. In 1989, autosomal dominant progressive external
      ophthalmoplegia with multiple deletions of mitochondrial DNA was the first of
      these disorders to be identified. Two years later, mtDNA depletion syndrome was
      initially reported in infants with severe hepatopathy or myopathy. The causes of
      these diseases are still unclear, but genetic linkage studies have identified
      three chromosomal loci for AD-PEO. Mitochondrial neurogastrointestinal
      encephalomyopathy (MNGIE), an autosomal recessive disorder associated with both
      mtDNA depletion and multiple deletions, is now known to be due to loss-of
      function mutations in the gene encoding thymidine phosphorylase. Increased plasma
      thymidine levels in MNGIE patients suggest that imbalanced nucleoside and
      nucleotide pools in mitochondria may lead to impaired replication of mtDNA.
      Future research will certainly lead to the identification of additional genetic
      causes of intergenomic communication defects and will likely provide insight into
      the normal "dialogue" between the two genomes.

PMID- 10885665
TI  - The role of mitochondria in the pathogenesis of neurodegenerative diseases.
AB  - A growing body of evidence indicates that mitochondrial dysfunction may play an
      important role in the pathogenesis of many neurodegenerative disorders. Because
      mitochondrial metabolism is not only the principal source of high energy
      intermediates, but also of free radicals, it has been suggested that inherited or
      acquired mitochondrial defects could be the cause of neuronal degeneration as a
      consequence of energy defects and oxidative damage. Mitochondrial respiratory
      chain dysfunction has been reported in association with primary mitochondrial DNA
      abnormalities, and also as a consequence of mutations in nuclear genes directly
      involved in mitochondrial functions, such as SURF1, frataxin, and paraplegin.
      Defects of oxidative phosphorylation and increased free radical production have
      also been observed in diseases that are not due to primary mitochondrial
      abnormalities. In these cases, the mitochondrial dysfunction is likely to be an
      epiphenomenon, which, nevertheless, could be of importance in precipitating a
      cascade of events leading to cell death. In either case, understanding the role
      of mitochondria in the pathogenesis of neurodegenerative diseases could be
      important for the development of therapeutic strategies in these disorders.

PMID- 10885666
TI  - April 2000: A 43 year old male with generalized epileptic seizures.

PMID- 10885667
TI  - May 2000: 35 year old male with a left temporal lobe mass.

PMID- 10885668
TI  - June 2000: 68 year old woman with clinical diagnosis of jugular paraganglioma.

PMID- 10885669
TI  - Sorting and targeting of melanosomal membrane proteins: signals, pathways, and
      mechanisms.
AB  - Newly synthesized melanosomal proteins, like many other cellular proteins,
      traverse through a series of intracellular compartments en route to melanosomes.
      Entry and exit of proteins through these compartments is orchestrated by cellular
      sorting machinery that recognize specific sorting signals. Melanosomal membrane
      proteins begin their intracellular journey upon co-translational importation into
      the endoplasmic reticulum (ER). The biosynthetic output of tyrosinase, the key
      melanogenic enzyme, appears to be regulated by quality-control events at the ER,
      the 'port of entry' to the secretory pathway. Following maturation in the ER and
      through the Golgi, the sorting of these proteins in the trans-Golgi network for
      intracellular retention and transport along endosome/lysosome pathway requires
      cytoplasmically exposed signals. A di-leucine motif, present in the cytoplasmic
      tails of most melanosomal proteins, and its interaction with adaptor protein (AP)
      complexes, specifically AP-3, are critical for these events. Defects in sorting
      signals and the cytosolic components that interact with these signals result in a
      number of murine coat color phenotypes and cause human pigmentary disorders.
      Thus, missense or frame-shift mutations that produce truncated tyrosinase lacking
      the melanosomal sorting signal(s) appear to be responsible for murine platinum
      coat color phenotypes and a proportion of human oculocutaneous albinism-1;
      mutations in AP-3 appear to be responsible for the mocha phenotype in mice and
      Hermansky-Pudlak-like syndrome in man. Additional signals and sorting steps
      downstream of AP-3 appear to be required for endosomal sorting and targeting
      proteins to melanosomes. Signals and mechanisms that sequester melanosomal
      proteins from endosomes/lysosomes are not understood. Potential candidates that
      mediate such processes include proteins encoded by lyst and pallid genes. The
      common occurrence of abnormalities in melanosomes in many storage-pool disorders
      suggests that melanocytes utilize signals, pathways, and mechanisms shared by
      other proteins and cell types to assemble a number of specialized proteins and
      produce unique cell-type-specific organelles.

PMID- 10885670
TI  - The melanocortin 1 receptor (MC1R): more than just red hair.
AB  - The melanocortin 1 receptor, a seven pass transmembrane G protein coupled
      receptor, is a key control point in melanogenesis. Loss-of-function mutations at
      the MC1R are associated with a switch from eumelanin to phaeomelanin production,
      resulting in a red or yellow coat colour. Activating mutations, in animals at
      least, lead to enhanced eumelanin synthesis. In man, a number of loss-of-function
      mutations in the MC1R have been described. The majority of red-heads (red-haired
      persons) are compound heterozygotes or homozygotes for up to five frequent loss
      of-function mutations. A minority of redheads are, however, only heterozygote.
      The MC1R is, therefore, a major determinant of sun sensitivity and a genetic risk
      factor for melanoma and non-melanoma skin cancer. Recent work suggests that the
      MC1R also shows a clear heterozygote effect on skin type, with up to 30% of the
      population harbouring loss-of-function mutations. Activating mutations of the
      MC1R in man have not been described. The MC1R is particularly informative and a
      tractable gene for studies of human evolution and migration. In particular, study
      of the MC1R may provide insights into the lightening of skin colour observed in
      most European populations. The world wide pattern of MC1R diversity is compatible
      with functional constraint operating in Africa, whereas the greater allelic
      diversity seen in non-African populations is consistent with neutral predictions
      rather than selection. Whether this conclusion is as a result of weakness in the
      statistical testing procedures applied, or whether it will be seen in other
      pigment genes will be of great interest for studies of human skin colour
      evolution.

PMID- 10885671
TI  - The use of expression profiling to study pigment cell biology and dysfunction.
AB  - Regulation of gene expression is a fundamental process by which cells respond to
      both intracellular and extracellular signals. For a pigment cell, alterations in
      gene expression regulate the processes of cell migration, lineage restriction,
      differentiation, type of pigment produced, and progression from a normal pigment
      cell to that of melanoma. To date, the identification of genes involved in normal
      pigment cell development has been accomplished by the cloning of individual
      mutant alleles, a single gene at a time. Current advances in technology have now
      made it possible to use expression profile analysis to investigate, on a genomic
      scale, the process of pigment cell development and function. This review compares
      and contrasts the methods of subtractive suppressive polymerase chain reaction
      (PCR) and differential display with that of cDNA microarray analysis.

PMID- 10885672
TI  - Latanoprost stimulates eumelanogenesis in iridial melanocytes of cynomolgus
      monkeys.
AB  - Latanoprost, the active principle of Xalatan eye drops, is a prostaglandin
      F2alpha analogue in widespread use for the treatment of glaucoma. During chronic
      treatment with the drug, an increased pigmentation of the iris was observed in
      both primates and man. To gain an insight into the nature of this effect, we
      analyzed the stroma of the irides of cynomolgus monkeys subjected to 25-38 weeks
      of treatment. A highly sensitive procedure, based on chemical degradation by
      alkaline hydrogen peroxide oxidation, or hydriodic acid hydrolysis, was
      developed, which allowed eumelanin and pheomelanin analysis of a single iris at a
      time. Untreated monkey irides were found to be essentially pheomelanic, providing
      further support to the recently reported occurrence of these pigments in human
      irides. In the Latanoprost-treated eyes, the amount of eumelanin increased from
      three to sevenfold, while the variation of pheomelanin did not exceed 25%. The
      increase in eumelanin/pheomelanin ratio in the treated eyes, as compared with the
      contralateral control eyes, varied from three to fivefold, and the change was
      statistically significant (P < 0.01; t-test). Based on the results of parallel
      studies, showing that Latanoprost does not induce proliferation of iridial
      melanocytes, and that the other pigmented layers of the iris which do not contain
      melanocytes are not affected by the drug, it can be concluded that the observed
      effect is a result of a direct interaction with the melanogenic mechanism. This
      probably involves activation of tyrosinase, as suggested, to account for the
      stimulation of melanin synthesis by related compounds, including natural
      prostaglandins.

PMID- 10885673
TI  - Melanophore lineage and clonal organization of the epidermis in Xenopus embryos
      as revealed by expression of a biogenic marker, GFP.
AB  - Melanophore lineage during embryogenesis of Xenopus laevis was traced using the
      overexpression of a biogenic marker, green fluorescent protein (GFP). Two
      different approaches were applied after injection of GFP mRNA (hence a marker
      construct) into each blastomere at the 16-cell stage. In in vivo experiments, the
      embryos injected with a marker construct were grown until stage 45, in which
      melanophores were distributed over the whole body and were good enough for
      checking GFP expression at their migratory destination. In in vitro experiments,
      neural tubes of the embryos injected with a marker construct were isolated and
      cultured at stage 21 to examine by virtue of GFP expression how neural crest
      cells differentiate into melanophores. The results obtained from both in vivo and
      in vitro experiments indicated the following: 1) selected animal blastomeres
      vastly contribute to the development of melanophores, whereas other animal
      blastomeres do so slightly at a limited pace; and 2) vegetal blastomeres never
      contribute to melanophores in normal development, whereas certain vegetal
      blastomeres have a potential to give rise to melanophores in vitro. The analyses
      using GFP also disclosed that the dorsal and ventral epidermis derive from the
      restricted animal blastomeres in the normal development. Since the dorso
      ventrality of the epidermis has been inseparably coupled with integumental
      pigmentation, the clonal organization of the epidermis observed in the present
      study is discussed in the light of pigment pattern formation attributed by
      melanophores.

PMID- 10885674
TI  - Development of early melanocytic lesions in transgenic mice predisposed to
      melanoma.
AB  - We have previously described a line of transgenic mice (TG3) that spontaneously
      develops heritable malignant melanoma. Histological analysis of these animals
      during the first postnatal month is described here. In the TG3 line, the number
      of melanocytes is increased at all anatomical sites to which neural-crest-derived
      melanocytes normally migrate. Clonal expansion and morphological changes of these
      melanocytes can be detected as early as postnatal day (PND) 15. By PND 30, cells
      morphologically indistinguishable from the tumor cells of adult transgenic mice
      were detected in the ear, eye lid and perianal region. These cells are believed
      to be the precursors of the primary tumors in adult mice. The stepwise
      development of melanoma in the TG3 line is similar to the stepwise development of
      melanoma in humans.

PMID- 10885675
TI  - Depigmenting effects of calcium D-pantetheine-S-sulfonate on human melanocytes.
AB  - The effects of calcium D-pantetheine-S-sulfonate (PaSSO3Ca) on human pigmentation
      were examined by in vitro assays using two types of human melanocytes: normal
      adult melanocytes (HNM) and M4Be melanoma cells. The compound, when added to a
      culture medium at doses indicating no cytotoxicity, causes a visually
      recognizable, reversible loss of pigment in both types of cells. Determination of
      melanin content, incorporation of 14C-DOPA into melanins and tyrosinase
      activities demonstrated that treatment of these cells with PaSSO3Ca resulted in a
      marked decrease in all three areas. When homogenates of these cells were assayed
      with lectins, the glycosylation pattern was modified, as tyrosinase activities
      were reduced in the cells treated with the compound. Immunoprecipitation of
      tyrosinase and tyrosinase-related protein 1 (Tyrp1 or TRP1) in cells incubated
      with radioactive glucosamine disclosed that glucosamine uptake by these enzymes
      was apparently increased, suggesting structural alterations in their sugar
      moieties. It is also noted that PaSSO3Ca is analogous in its chemical structure
      to Coenzyme A (CoA), which plays an important role in the intracellular transport
      of proteins. Based on these findings, it is likely that the compound exerts its
      depigmenting effects in human pigment cells through the modification of
      glycosylation of tyrosinase and TRP1, which are key enzymes for melanogenesis.

PMID- 10885676
TI  - Induction of melanogenesis by tetradecanoylphorbol-13 acetate and endothelin 3 in
      embryonic avian peripheral nerve cultures.
AB  - In this study, we have analyzed the melanogenic potential of Schwann cells using
      in vitro cell cultures of embryonic quail peripheral nerves. It is shown that in
      Schwann cells, two factors, 12-O-tetradecanoylphorbol-13 acetate (TPA) and
      endothelin 3, trigger a differentiation pathway toward melanocytes, and that
      Steel factor has no effect on these cells unless treated simultaneously with TPA.
      In these cultures, TPA induces the expression of c-kit, whereas Steel factor
      enhances the development of melanocytes. In the assay system we employed, neither
      neuronal nor catecholaminergic phenotypes were obtained, regardless of various
      combinations of related factors added to the culture medium. These data support
      our previous observations indicating the existence of bipotent progenitors that
      are capable of differentiating into Schwann cells or into melanocytes, and the
      regulatory role of endothelin 3 on those precursors, as revealed by the clonal
      culture of neural crest cells.

PMID- 10885677
TI  - Probing the building blocks of eumelanins using scanning electron microscopy.
AB  - Scanning electron microscopy (SEM) is used to examine the structure of natural
      and synthetic melanins. Eumelanin from Sepia officinalis and synthetic eumelanin
      are found to be structurally dissimilar. The natural sample has a significant
      structural order with subunits that have a lateral dimension of approximately 15
      nm. The synthetic samples, on the other hand, appear to be amorphous solids.
      These results lend support for the existence of fundamental structural units
      proposed from the analyses of wide-angle X-ray diffraction measurements and
      previous mass-spectrometry results. These findings also provide insight into the
      disparate photophysical behavior of Sepia and synthetic eumelanin.

PMID- 10885678
TI  - Detection of circulating melanoma cells by RT-PCR amplification of three
      different melanocyte-specific mRNAs in a mouse model.
AB  - Three different melanocyte-specific mRNAs are studied as potential markers for
      circulating melanoma cells in the serum of mice inoculated subcutaneously with
      B16F10 melanoma cells. These three mRNAs encode tyrosinase, tyrosinase related
      protein-2 (TRP-2) and Pmel17, proteins that are essential for the synthesis of
      melanin and are expressed specifically in melanocytes. We used reverse
      transcription polymerase chain reaction (RT-PCR) to detect these three different
      melanocyte-specific mRNAs in the sera of B16F10 bearing mice. Since melanocytes
      would not normally be present in the blood, the detection of those transcripts
      should indicate the presence of circulating melanoma cells. RT-PCR detection of
      all three mRNAs was highly sensitive and specific. Our in vitro studies show that
      as few as 10 melanoma cells can be detected in 125 microl blood and that in vivo,
      melanoma cells can be detected in blood samples from B16F10 melanoma bearing
      mice. Of these three mRNAs, Pmel17 mRNA is the most sensitive marker for
      detecting circulating melanoma cells compared with tyrosinase mRNA and TRP-2
      mRNA. Moreover, this mouse model might be useful for basic research of malignant
      melanoma patients with haematogenous metastasis.

PMID- 10885679
TI  - The responses of the human epidermal melanocyte system to chronic erythemal doses
      of UVR in skin protected by topical applications of a combination of vitamins C
      and E.

PMID- 10885680
TI  - Task switching and attention deficit hyperactivity disorder.
AB  - The main goal of the present set of studies was to examine the efficiency of
      executive control processes and, more specifically, the control processes
      involved in task set inhibition and preparation to perform a new task in
      attention deficit hyperactivity disorder (ADHD) and non-ADHD children. This was
      accomplished by having ADHD children, both on and off medication, and non-ADHD
      children perform the task-switching paradigm, which involves the performance of
      two simple tasks. In nonswitch trials, an individual task is performed repeatedly
      for a number of trials. In switch trials, subjects must rapidly and accurately
      switch from one task to the other, either in a predictable or unpredictable
      sequence. Switch costs are calculated by subtracting performance on the nonswitch
      trials from performance on the switch trials. These costs are assumed to reflect
      the executive control processes required for the coordination of multiple tasks.
      ADHD children showed substantially larger switch costs than non-ADHD children.
      However, when on medication, the ADHD children's switch performance was
      equivalent to control children. In addition, medication was observed to improve
      the ADHD children's ability to inhibit inappropriate responses. These data are
      discussed in terms of models of ADHD and cognition.

PMID- 10885681
TI  - Confirmation of an inhibitory control deficit in attention-deficit/hyperactivity
      disorder.
AB  - The objective of this study was to determine whether deficient inhibitory control
      distinguishes children with a diagnosis of attention-deficit/hyperactivity (ADHD)
      disorder, conduct disorder (CD), and comorbid ADHD + CD from normally developing
      children. Participants were rigorously diagnosed children (age 7 to 12 years)
      with ADHD (N = 72), CD (N = 13) or ADHD + CD (N = 47) and 33 control children
      (NC). We studied inhibitory control using the stop-signal paradigm, a laboratory
      task that assessed the ability to inhibit an ongoing action. The ADHD group had
      significantly impaired inhibitory control compared to NC, CD, and ADHD + CD
      children. These results indicate that children with ADHD have deficient
      inhibition as measured in the stop-signal paradigm and that ADHD occurring in the
      presence of ADHD + CD may represent a phenocopy of CD rather than a variant of
      ADHD.

PMID- 10885682
TI  - Naming speed performance and stimulant effects indicate effortful, semantic
      processing deficits in attention-deficit/hyperactivity disorder.
AB  - This study investigated rapid automatized naming and effects of stimulant
      medication in school-age children with attention-deficit/hyperactivity disorder
      (ADHD) with and without concurrent reading disorder (RD). Two ADHD groups (67
      ADHD only; 21 ADHD + RD) and a control group of 27 healthy age-matched peers were
      compared on four variables: color naming speed, letter naming speed, phonologic
      decoding, and arithmetic computation. Discriminant function analysis (DFA) was
      conducted to predict group membership. The four variables loaded onto two
      discriminant functions with good specificity: phonologic decoding, letter naming
      speed, and arithmetic defined the first function; color naming speed defined the
      second function. Both ADHD groups were significantly slower in color naming than
      controls, but did not differ from one another. DFA correctly classified 96% of
      the control group, 91% of ADHD + RD, and 82% of ADHD only. A subset of children
      in the ADHD groups participated subsequently in an acute, randomized, placebo
      controlled, crossover trial with three single doses (10, 25, 20 mg) of
      methylphenidate. Methylphenidate selectively improved color-naming speed but had
      no effect on the speed of naming letters or digits. These findings challenge the
      tenet that naming speed deficits are specific to RD and implicate naming speed
      deficits associated with effortful semantic processing in ADHD, which are
      improved but not normalized by stimulant medication.

PMID- 10885683
TI  - Multimethod psychoeducational intervention for preschool children with disruptive
      behavior: two-year post-treatment follow-up.
AB  - This paper describes the 2-year post-treatment follow-up of preschool children
      identified as having high levels of disruptive behavior at kindergarten entry.
      They were assigned to four treatment conditions: A no-treatment group, parent
      training only, treatment classroom only, and the combination of parent training
      with the treatment classroom. Interventions lasted the entire kindergarten
      academic year. Initial post-treatment results reported previously indicated no
      effects for the parent-training program but some efficacy for the classroom
      intervention program. For this report, the disruptive behavior (DB) children were
      subdivided into those who did (n = 74) and did not (n = 77) receive the treatment
      classroom. Two-year post-treatment follow-up results indicated no differences
      between the classroom treated and untreated DB groups. These groups also failed
      to differ in the percentage of children using available treatments across the
      follow-up period. The DB children in both groups had significantly more symptoms
      of ADHD and ODD than a community control group (N = 47) at follow-up. They also
      received higher ratings of externalizing problems on the parent Child Behavior
      Checklist, more severe ratings of behavior problems at home, and ratings of more
      pervasive behavior problems at school, and had poorer academic skills. Results
      suggested that early intervention classrooms for DB children may not produce
      enduring effects once treatment is withdrawn, and that better approaches are
      needed for identifying those DB children at greatest risk for later
      maladjustment.

PMID- 10885684
TI  - Oppositional children differ from healthy children in frontal brain activation.
AB  - An atypical EEG pattern of frontal brain activation, which has been found in
      children and adults with emotional disorders, also is hypothesized to be present
      in disruptive behavior disorders. One hundred nineteen children (4 1/2 and 8
      years of age) were examined with regard to the following questions: (1) Do
      children who are diagnosed with oppositional defiant disorder (ODD) exhibit an
      atypical pattern of frontal brain activation? (2) Can this pattern be
      demonstrated in preschool children (4 1/2 years of age) as well as in school
      children (8 years)? (3) Are there gender differences in these patterns similar to
      those that have been demonstrated in adults? Spontaneous EEG activity was
      subjected to power spectral analysis. In oppositional preschool and elementary
      school girls, the well-known pattern of lower left frontal than right frontal
      activation emerged that has been found previously in emotionally disordered
      children. Healthy girls showed no frontal brain asymmetry at 4 1/2 years of age,
      and left frontal activation at 8 years. In contrast, healthy boys demonstrated a
      greater right than left frontal activation, whereas ODD boys did not display any
      frontal brain asymmetry. Thus, the pattern of frontal brain activation seems to
      be gender-specific. The atypical activation pattern in oppositional children is
      hypothesized to be a biological substrate of negative affective style.

PMID- 10885685
TI  - External validity of conduct and oppositional defiant disorders determined by the
      NIMH Diagnostic Interview Schedule for children.
AB  - We administered the Diagnostic Interview Schedule for Children (DISC) two times
      to a group of youth (222 boys, 147 girls) entering residential care, once at
      their time of entry and once 1 year later. We then compared their DISC outcomes
      on Conduct Disorder (CD) and Oppositional Defiant Disorder (ODD) against changes
      in independent direct observations of diagnostically relevant behavior obtained
      over the course of that year. Results from hierarchical linear modeling analyses
      showed significant discriminative relationships between results from the DISC and
      the independent observations. Specifically, observations of symptomatic behaviors
      (CD or ODD) decreased for youth who met diagnostic criteria at the first
      administration of the DISC but not at the second, increased for youth who did not
      meet criteria at the first administration but did at the second, and did not
      change for youth who met criteria at both administrations. These results extend
      the data on the validity of the DISC and support continued research efforts to
      determine its clinical utility.

PMID- 10885686
TI  - Psychometric study of the Child and Adolescent Functional Assessment Scale:
      prediction of contact with the law and poor school attendance.
AB  - The predictive validity of the Child and Adolescent Functional Assessment Scale
      (CAFAS) is investigated using the data set generated by the national evaluation
      of the demonstration service grants funded by the Center for Mental Health
      Services. Logistic regressions were performed separately for contact with the law
      and poor school attendance, which were both assessed at 6 months postintake.
      Other variables included in the model besides the CAFAS total score at intake
      were age, gender, and family risk factors. The results show that the CAFAS total
      score at intake was a positive predictor of the likelihood of contact with the
      law and poor school attendance, even after controlling for age, gender, and risk
      factors. Furthermore, the CAFAS total score was predictive even after excluding
      scores on CAFAS subscales, which may have been influenced by absenteeism or
      delinquency. These findings are consistent with recent research indicating that
      the CAFAS predicts recidivism in juvenile delinquents.

PMID- 10885687
TI  - Relations of tripartite dimensions of emotion to childhood anxiety and mood
      disorders.
AB  - This study examined preliminary higher-order models relating tripartite
      dimensions of emotion to severity of anxiety and depressive disorders in 100
      clinically referred children and adolescents. In light of the accumulating
      support for multifactor models of vulnerability and negative emotion in children,
      the present investigation was designed to establish preliminary estimates of the
      structure and magnitude of the relations of three emotion factors with dimensions
      of social anxiety, depression, panic, generalized anxiety,
      obsessions/compulsions, and separation anxiety. Results were consistent with
      structures that minimally specified two higher-order emotion factors, yet only
      some parameter estimates were consistent with theory regarding the tripartite
      model. Problems with the measurement of tripartite factors and possibilities for
      further research are outlined.

PMID- 10885688
TI  - Positron emission tomography with fluorine-18 fluorodeoxyglucose to evaluate
      response of early breast carcinoma treated with stereotaxic interstitial laser
      therapy.
AB  - Stereotaxic interstitial laser therapy is a promising new alternative to surgery
      to treat early-stage breast cancer. With this, laser energy coagulates the tumor
      with controlled heat, leading to fibrosis. Fluorodeoxyglucose positron emission
      tomography (FDG PET) scanning was performed in four patients treated by this
      technique to determine the degree of necrosis after interstitial laser therapy.
      The results showed that FDG PET scanning was in close agreement with
      histopathologic findings, confirming complete necrosis in one patient and
      variable response in the other three patients. Uptake of FDG appears to be a
      reliable means to monitor treatment response after interstitial laser therapy and
      may be useful in the management of breast cancer when used with this new
      procedure.

PMID- 10885689
TI  - Permanent iatrogenic vocal cord paralysis after I-131 therapy: a case report and
      literature review.
AB  - A patient who underwent I-131 therapy for a solitary toxic thyroid nodule
      subsequently experienced vocal cord paralysis, a rare complication. The patient
      was examined because of hoarseness 1 week after treatment. Indirect laryngoscopy
      at the time confirmed right vocal cord paralysis. When the examination was
      repeated in 6 months, no improvement was noted; vocal cord paralysis was then
      declared permanent. Surprisingly, 11 months after the onset of symptoms, the
      patient observed improvement in her voice. At 14 months, she experienced complete
      vocal recovery. However, a computed tomography performed after this showed that
      her right vocal cord paralysis was unresolved. The apparent complete recovery of
      her voice is believed to be a result of adaptive compensatory mechanisms.
      Patients who recover from hoarseness after injury to the recurrent laryngeal
      nerve should have cord function documented by indirect laryngoscopy or other
      means before the physician performs a procedure that could harm the contralateral
      nerve, because damage to this nerve could result in devastating consequences.

PMID- 10885690
TI  - Growing hepatic cavernous hemangioma demonstrated by Tc-99m red blood cell
      scintigraphy.
AB  - Hepatic cavernous hemangiomas rarely grow. Although a few cases have been
      reported in the literature, none used Tc-99m red blood cell scintigraphy. The
      authors describe such a case here.

PMID- 10885691
TI  - Tc-99m erythrocyte localization of an intramuscular hemangioma of the arm.
AB  - An unusual case of intramuscular hemangioma of the left triceps muscle is
      presented. This tumor may infiltrate the muscle and be misdiagnosed as a
      malignant neoplasm.

PMID- 10885692
TI  - Hepatic lesion differentiated from accessory spleen by a heat-damaged red blood
      cell scan.
AB  - A 34-year-old woman referred for evaluation of an abdominal mass underwent a
      computed tomographic portagram that showed a large mass in the region of the left
      hepatic lobe and adjacent to the spleen. A liver-spleen scan with sulfur colloid
      did not clearly show whether the mass originated in the liver or the spleen. To
      evaluate the possibility of an accessory spleen, a selective spleen scan using Tc
      99m-labeled heat-damaged red blood cells was performed and showed intense uptake
      in the region of the spleen only. The patient underwent surgical exploration and
      excision of the lesion, which proved to be focal nodular hyperplasia of the
      liver. Thus, the heat-damaged red blood cell scan ruled out an accessory spleen
      as a cause for the mass.

PMID- 10885693
TI  - Use of Tc-99m HMPAO leukocyte scans to evaluate bone infection: incremental value
      of additional SPECT images.
AB  - PURPOSE: In this study, the diagnostic value of Tc-99m hexamethylpropylene amine
      oxime (HMPAO) leukocyte scans and the role of additional SPECT in the diagnosis
      of bone infection were evaluated. MATERIALS AND METHODS: The Tc-99m HMPAO
      leukocyte scans of 37 patients with clinically suspected bone infection were
      reviewed. The patients were divided into two groups according to the presence of
      orthopedic implants. Early (4 to 6 hours) and delayed (18 to 20 hours) planar
      images and early SPECT images were obtained. The final diagnosis of infection was
      made based on the pathologic, bacteriologic, and surgical data and clinical
      follow-up. RESULTS: Group 1 (25 patients with orthopedic implants) included 15
      true-positive, 1 false-negative, 7 true-negative, and 2 false-positive results.
      Group 2 (12 patients without orthopedic implants) included 7 true-positive, 1
      false-negative, and 4 true-negative results. The overall sensitivity of the Tc
      99m HMPAO leukocyte scan with SPECT to detect bone infection was 92%, with a
      specificity rate of 85%. (Group 1: sensitivity, 94%; specificity, 78%. Group 2:
      88% and 100% sensitivity and specificity, respectively.) CONCLUSION: The Tc-99m
      HMPAO leukocyte scan is useful in the diagnosis of bone infection, regardless of
      the presence of orthopedic implants. The additional SPECT images may be helpful
      to localize the site of infection more accurately.

PMID- 10885694
TI  - Parathyroid imaging with pertechnetate plus perchlorate/MIBI subtraction
      scintigraphy: a fast and effective technique.
AB  - We set up a modified technetium-99m (Tc-99m) pertechnetate/Tc-99m MIBI (Tc-MIBI)
      subtraction scintigraphy for parathyroid imaging by introducing the use of
      potassium perchlorate (KCLO4). Initially, the effect of KCLO4 on technetium
      thyroid wash-out was evaluated in five healthy volunteers: 40-minute dynamic
      studies of the thyroid were obtained 20 minutes after the injection of technetium
      150 MBq (4 mCi), both in baseline conditions and after the oral administration of
      400 mg KCLO4. After an average latency time of 10.5 minutes, KCLO4 administration
      resulted in fast and relevant technetium thyroid wash-out with a mean half-time
      of 16.2 minutes (the half-time was 142.8 minutes in baseline conditions), and a
      40-minute reduction of thyroid activity of 78% (it was 14% in baseline
      conditions). Based on these findings, a new Tc-MIBI subtraction procedure was
      established as follows: 1) 150 MBq technetium (4 mCi) injection; 2) 400 mg KCLO4
      administered orally; 3) patient neck immobilization; 4) acquisition of a 5-minute
      technetium thyroid scan; 5) 500 MBq MIBI (13.5 mCi) injection; 6) acquisition of
      a sequence of seven MIBI images, each lasting 5 minutes; and 7) processing (image
      realignment when necessary, background subtraction, normalization of MIBI images
      to the maximum pixel count of the technetium image, and subtraction of the
      technetium image from the MIBI images). In addition, high-resolution neck
      ultrasound (US) was performed in all cases on the same day as the scintigraphic
      evaluation. Eighteen consecutive patients with primary hyperparathyroidism were
      enrolled in the study. Tc-MIBI scintigraphy revealed a single adenoma in all
      cases and US showed this finding in 15 of 18 cases (83.3%). Furthermore, in three
      patients, a thyroid nodule associated with hyperparathyroidism was detected by
      technetium thyroid scans and neck US. In all patients, the parathyroid adenoma
      was easily identified on both the 20- to 40-minute MIBI and subtracted (MIBI-Tc)
      images. Regarding the scintigraphic parameters, no difference was found between
      parathyroid adenomas located in the region of the thyroid bed or in ectopic sites
      and in parathyroid adenomas with a retrothyroid location. Surgical findings
      confirmed the presence of a single parathyroid adenoma in all cases. In the three
      patients with a concomitant thyroid nodule, thyroid lobectomy was performed.
      These preliminary data suggest that 1) double-tracer subtraction scintigraphy,
      combined with neck US, appears to be the preferable preoperative imaging
      procedure in hyperparathyroidism patients with concomitant thyroid nodular
      disease, 2) in the Tc-MIBI parathyroid scan, the use of KCLO4 results in a rapid
      and relevant technetium thyroid clearance, improving the quality of MIBI images
      and making the visualization of parathyroid adenomas, particularly those located
      behind the thyroid gland, easier.

PMID- 10885695
TI  - Dichotomy between Tc-99m MDP bone scan and fluorine-18 fluorodeoxyglucose
      coincidence detection positron emission tomography in patients with non-Hodgkin's
      lymphoma.
AB  - The authors report two cases of non-Hodgkin's lymphoma that were evaluated not
      only by conventional staging work-up but also additional Tc-99m MDP bone scans
      and fluorine-18 fluorodeoxyglucose (F-18 FDG) coincidence detection (CoDe)
      positron emission tomographic (PET) imaging. There were discordant results
      between the Tc-99m MDP bone scans and F-18 FDG CoDe PET. In the first case, the
      bone marrow biopsy was positive, and F-18 FDG CoDe PET was consistent with a
      malignancy, but the findings of the Tc-99m MDP bone scintiscan were negative. In
      the second case, the bone marrow biopsy was negative, but F-18 FDG CoDe PET
      revealed focal skeletal involvement, which improved markedly on the follow-up
      study after chemotherapy. If skeletal involvement has a focal distribution and is
      confined to the marrow cavity, both bone marrow biopsy and bone scintigraphy can
      be falsely negative. In this situation, F-18 FDG PET is useful and revealing.

PMID- 10885696
TI  - Late blood pool images after Tc-99m tetrofosmin injection in a patient with
      monoclonal gammopathy of uncertain significance and immunologic disorders.
AB  - The authors report a case of abnormal biodistribution of Tc-99m tetrofosmin in a
      patient with immunologic disorders who underwent rest-stress myocardial perfusion
      scintigraphy to assess the operative risk for surgery of possible relapse of
      adenocarcinoma of the left maxillary sinus. The patient had monoclonal gammopathy
      of uncertain significance with a serum electrophoretic pattern of both monoclonal
      immunoglobulin A and free kappa light chain components and a mild form of
      idiopathic immunohemolytic anemia. Two different images at rest after injection
      of Tc-99m tetrofosmin showed a typical blood-pool pattern with absence of
      detectable myocardial uptake. Other patients injected with the same batch of
      radiopharmaceutical showed myocardial uptake. A change of the molecular
      characteristics of tetrofosmin after the injection could not be a factor, because
      the values of the main chemical and physical parameters of the blood were in the
      normal range. Accordingly, the authors propose the hypothesis that the monoclonal
      immunoglobulin A or the free kappa light chains of this patient accidentally
      recognized one or more epitopes of the tetrofosmin molecule, binding it with high
      affinity and causing an abnormal biodistribution, characterized by late blood
      pool imaging. No similar experiences have been described in the scientific
      literature.

PMID- 10885697
TI  - Abnormally increased uptake in the palm and the thumb as the result of a bone
      imaging agent injection into the radial artery.
AB  - The "glove" phenomenon is caused by arterial injection of a bone-imaging agent
      into the antecubital fossa. The authors describe a patient who incidentally
      received an arterial injection of bone-imaging agent into the right distal radial
      artery near the wrist, which resulted in a "hot" palm and thumb. The phenomenon
      of hot palm and thumb can be explained by normal anatomic-physiologic blood flow
      after radial artery injection. The radial artery contributes the blood supply to
      the thumb through the dorsal metacarpal arteries of the first metacarpals, and
      the dorsal carpal branch of the radial artery, a branch of the interosseous
      artery, and dorsal carpal branch of the ulnar artery form the dorsal carpal rete.
      The normal vascular anatomic-physiologic dynamic constituted the mixture and
      dilution effects after the distal radial artery injection that resulted in hot
      areas limited to the palm and thumb of the hand on bone scintigraphy.

PMID- 10885698
TI  - Atlas on acute pyelonephritis in children.
AB  - The authors describe various patterns of Tc-99m DMSA images that correspond to a
      diagnosis of acute pyelonephritis. Only those children with complete
      scintigraphic healing or considerable improvement after 6 months have been
      considered.

PMID- 10885699
TI  - Technetium-99m sestamibi SPECT imaging of bilateral pulmonary carcinoid tumors.

PMID- 10885700
TI  - The use of Technegas in the detection of a bronchopleural fistula.

PMID- 10885701
TI  - Breast metastasis of non-Hodgkin's lymphoma: evaluation with Ga-67 scintigraphy.

PMID- 10885702
TI  - Increased activity in benign phyllodes tumor on Tc-99m MDP scintimammography.

PMID- 10885703
TI  - Coincidental finding of crossed fused renal ectopia detected on bone
      scintigraphy.

PMID- 10885704
TI  - Mannitol as an alternative to furosemide in Tc-99m MAG3 diuretic renography: a
      case report.

PMID- 10885705
TI  - An isolated digital metastasis of esophageal basaloid squamous cell carcinoma.

PMID- 10885706
TI  - Tc-99m MDP three-phase bone scintigraphy in disciplinary exercise-induced
      rhabdomyolysis.

PMID- 10885707
TI  - Increased fluorodeoxyglucose uptake in a calf opposite to a leg with osteosarcoma
      after operation.

PMID- 10885708
TI  - Acquired bile duct blockage: entry of hepatobiliary agent into an intrahepatic
      abscess.

PMID- 10885709
TI  - Unusual presentation of hepatocellular carcinoma and assisted diagnosis by liver
      scan.

PMID- 10885710
TI  - Paradoxical restoration of hepatic uptake of Ga-67 after aggressive chemotherapy
      in a case of mesenteric malignant lymphoma.

PMID- 10885711
TI  - Lymphoma mimicking a psoas abscess on Ga-67 scintigraphy.

PMID- 10885712
TI  - Current readings in nuclear medicine.

PMID- 10885713
TI  - A thirty-year odyssey in nitrogen metabolism: from ammonium to dipeptides.

PMID- 10885714
TI  - Semiquantitative culture of subcutaneous segment for conservative diagnosis of
      intravascular catheter-related infection.
AB  - BACKGROUND: Sensitivity and negative predictive values of combined surface
      cultures (skin and hub) are high in the presumptive diagnosis of catheter-related
      infection, but specificity and PPVs are poor. The purpose of the study was to
      evaluate the yield of the semiquantitative culture of the subcutaneous segment in
      the diagnosis of colonization of the catheter tip without removal of the
      catheter. METHODS: A prospective study was performed in 124 nontunneled central
      venous catheters that were removed because of suspected infection or the end of
      therapy. Catheter colonization was considered if >15 colony-forming units (CFU)
      in the roll procedure or > 1,000 CFU in the quantitative Cleri procedure were
      recovered from the tip cultures ("gold standard"). Before removing the catheter,
      a semiquantitative culture of skin surrounding the point of insertion, a
      semiquantitative culture of the subcutaneous segment (after removing the catheter
      only 2 cm), a semiquantitative cultures of the hub, and a pareated quantitative
      blood culture were performed. Receiver operating characteristic curves were
      calculated to estimate the cutoff points, and a culture was considered positive
      when CFUs were > or =15, > or =15, and > or =5 for skin, hub, and subcutaneous
      segment cultures, respectively. RESULTS: Catheter colonization was detected in 51
      catheters. The mean duration of catheterization was 14 +/- 8 days, and the rates
      of incidence of tip colonization and bacteremia were 2.9 per 100 catheter days
      and 1.2 per 100 catheter days, respectively. Sensitivity of skin, subcutaneous,
      and hub cultures analyzed individually were < or =61%; however, specificity and
      positive predictive values (PPVs) of subcutaneous segment cultures were
      significantly higher than skin cultures (94% and 88.5% vs 71.6% (p = .001) and
      62% (p = .014), respectively). Sensitivity of the combined skin and hub cultures
      and of the combined subcutaneous segment and hub cultures were similar: 86.2% and
      84.3%, respectively; however, specificity and PPVs of this latter combination
      were significantly higher than former: 82% and 78.1% vs 59.7% (p = .008) and
      61.9% (p = .07), respectively. The likelihood ratio of a positive test for the
      combined subcutaneous segment and hub culture was 4.68, and only 2.13 for the
      combined skin and hub culture. CONCLUSIONS: These results indicate that the
      combined subcutaneous segment and hub culture constitutes an easy, effective
      procedure for the conservative diagnosis of catheter colonization.

PMID- 10885715
TI  - Effect of alanyl-glutamine on leucine and protein metabolism in endotoxemic rats.
AB  - BACKGROUND: Branched-chain amino acids (BCAA; valine, leucine, and isoleucine)
      have a regulatory effect on protein metabolism and are the main donor for
      synthesis of alanine and glutamine in the skeletal muscle. This study was
      performed to investigate whether exogenous alanine or glutamine would affect
      leucine and protein metabolism in intact and endotoxemic rats. METHODS: Rats were
      injected with endotoxin of Salmonella enteritidis or saline. Thirty minutes
      later, the effects of endotoxemia and L-alanyl-L-glutamine (AG) on leucine and
      protein metabolism were evaluated using a primed constant infusion of [1
      14C]leucine, endotoxin, and AG (200 mg/mL) solution or an infusion of [1
      14C]leucine without endotoxin or AG. The specificity of the effect of exogenous
      alanine and glutamine was evaluated by a single infusion of alanine, glutamine,
      and glycine in a separate study. RESULTS: Endotoxin treatment induced more
      negative net protein balance caused mainly by an increase in whole-body
      proteolysis. Protein synthesis increased in kidneys, colon, and spleen, while a
      decrease was observed in skeletal muscle. The impressive effects of AG were the
      decrease in plasma branched-chain amino acid (BCAA) levels, decrease in leucine
      oxidized fraction, and improvement of protein balance associated with a decrease
      in whole-body proteolysis. Similar changes in leucine and protein metabolism were
      induced by infusion of alanine or glutamine but not by infusion of glycine.
      CONCLUSIONS: IV administration of alanine or glutamine improves protein balance
      and decreases leucine oxidized fraction in postabsorptive state and in
      endotoxemia. Decreased proteolysis is the main cause of decreased plasma BCAA
      levels after AG treatment.

PMID- 10885717
TI  - Medium-chain, triglyceride-containing lipid emulsions increase human neutrophil
      beta2 integrin expression, adhesion, and degranulation.
AB  - BACKGROUND: To test the hypothesis that lipid emulsions with different
      triglyceride structures have distinct immunomodulatory properties, we analyzed
      human neutrophil adhesion and degranulation after lipid incubation. METHODS:
      Neutrophils, isolated from the blood of 10 healthy volunteers, were incubated in
      medium or physiologic (2.5 mmol/L) emulsions containing long-chain (LCT), medium
      chain (MCT), mixed LCT/MCT, or structured (SL) triglycerides. Expression of
      adhesion molecules and degranulation markers was evaluated by flow cytometry.
      Also, functional adhesion was investigated by means of a flow cytometric assay
      using fluorescent beads coated with the integrin ligand intercellular adhesion
      molecule (ICAM)-1. RESULTS: Although LCT and SL had no effect, LCT/MCT
      significantly increased expression of the beta2 integrins lymphocyte-function
      associated antigen 1 (+18%), macrophage antigen 1 (+387%), p150,95 (+82%), and
      (alphaDbeta2 (+230%). Degranulation marker expression for azurophilic (CD63,
      +210%) and specific granules (CD66b, +370%) also significantly increased, whereas
      L-selectin (CD62L, -70%) decreased. The effects of LCT/MCT were mimicked by the
      MCT emulsion. ICAM-1 adhesion (% beads bound) was increased by LCT/MCT (34% +/-
      4%), whereas LCT (19% +/-3%) and SL (20% +/- 2%) had no effect compared with
      medium (17% +/- 3%). CONCLUSIONS: LCT/MCT and MCT, contrary to LCT and SL
      emulsions, increased neutrophil beta2 integrin expression, adhesion, and
      degranulation. Apart from other emulsion constituents, triglyceride chain length
      might therefore be a key feature in the interaction of lipid emulsions and the
      phagocyte immune system.

PMID- 10885716
TI  - Brain manganese deposition and blood levels in patients undergoing home
      parenteral nutrition.
AB  - BACKGROUND: Extrapyramidal syndrome and alterations in brain magnetic resonance
      images are described in patients undergoing long-term home parenteral nutrition
      (HPN) and in cholestatic patients. These abnormalities have been correlated to
      basal ganglia manganese (Mn) accumulation. METHODS: A longitudinal 1-year study
      was conducted on 15 patients undergoing HPN (median duration, 3.8 years; range,
      1.7-10; median Mn parenteral supplementation, 0.1 mg/d). Whole-blood, plasma,
      intra-erythrocytes, and urinary Mn concentrations were measured and brain
      magnetic resonance was performed at the beginning (time 0) and after 1 year of Mn
      intravenous supplementation withdrawal (time 1). No patients showed psychosis,
      extrapyramidal syndrome, or cholestasis. RESULTS: At time zero, 10 of 15 patients
      (67%) showed paramagnetic accumulation on cerebral magnetic resonance images; at
      time 1 there was a reduction of cerebral Mn accumulation. In all patients, blood
      Mn levels were significantly reduced after 1 year of Mn intravenous
      supplementation withdrawal. CONCLUSIONS: Patients receiving long-term HPN showed
      an elevated incidence of alterations in brain magnetic resonance images with a
      median Mn intravenous supplementation of 0.1 mg/d. Mn supplementation withdrawal
      significantly decreased metal levels in blood and brain storage. We noticed that
      the intra-erythrocyte Mn level was a good index of Mn status.

PMID- 10885718
TI  - Renal function and urinary excretion of electrolytes in patients receiving cyclic
      parenteral nutrition.
AB  - BACKGROUND: Long-term parenteral nutrition (LTPN) has been shown to induce renal
      impairment and bone demineralization. However, the mechanism of both injuries has
      not been clarified. METHODS: This prospective study was performed in 16 patients
      with short bowel syndrome, aged 28 to 63 years, who had received LTPN for 31 +/-
      7 months. Urinary excretion of electrolytes were measured before (diurnal, 12
      hours) and during (nocturnal, 12 hours) parenteral nutrition. Glomerular
      filtration rate (GFR) and effective renal plasma flow (ERPF) were measured in the
      morning after the nutritional bag supply. RESULTS: Mean GFR was 86 +/- 7
      mL/min/1.73 m2 and ERPF was 412 +/- 31 mL/min/1.73 m2. Decreased GFR was present
      in 9 patients. There was no relation between renal function and age or the
      duration of LTPN. Urine volume and excretion of urea, creatinine, sodium,
      magnesium, and phosphate but not potassium increased significantly in nocturnal
      urine compared with diurnal urine. On the basis on 24-hour calciuria, 7 patients
      were normocalciuric (NCa) whereas 9 were hypercalciuric (HCa). Both had excessive
      nocturnal calciuria, but only the HCa group had diurnal hypercalciuria, the
      calcium supply being identical. Bone mineral density (BMD) was slightly, although
      not significantly, higher in NCa group, but in all patients BMD correlated
      significantly with calciuria. Serum parathyroid hormone and vitamin D were not
      different in the two groups. CONCLUSIONS: In patients receiving LTPN, renal
      function is frequently impaired, by a mechanism which remains unclear. In
      nocturnal cyclic mode of nutrition, urinary volume and electrolyte excretion
      occurred predominantly during the infusion, but some patients have diurnal
      hypercalciuria. In these patients a defect in renal calcium reabsorption or more
      likely the inability of bone to retain the infused calcium may be responsible for
      bone demineralization.

PMID- 10885719
TI  - Spontaneous transpyloric migration of a ballooned nasojejunal tube: a randomized
      controlled trial.
AB  - BACKGROUND: Spontaneous transpyloric migration of a simple nasojejunal tube (NJT)
      can be expected in only one-third of insertions. Guidance of the tube by
      radiologic or endoscopic maneuvers is usually required. We believed that locating
      a 5-mL balloon near the tip of an NJT on which natural peristalsis could act
      would improve the rate of spontaneous transpyloric migration and facilitate small
      bowel propagation. METHODS: Thirty healthy volunteers were randomly assigned to
      have an inflated or noninflated, ballooned NJT fashioned from a modified 9F
      Hickman line catheter inserted. The pH of aspirates was measured hourly and the
      final location of the tube assessed by gastrografin contrast abdominal x-ray
      (AXR) at the end of 6 hours, at which time the tube was removed. RESULTS: After 6
      hours, spontaneous transpyloric migration occurred in 86.6% of the ballooned and
      66.6% of the nonballooned tubes. The final disposition of the ballooned tubes
      was: stomach, 2 (13.3%); duodenum, 1 (6.7%); and small bowel, 12 (80%). The final
      disposition of the nonballooned tubes was: stomach, 5 (33%), NS; duodenum, 9
      (60%), p < .05; and small bowel, 1 (6.7%), p < .05. CONCLUSIONS: Ballooned NJT
      have a higher rate of spontaneous transpyloric migration and are significantly
      more likely to achieve an optimal small bowel location.

PMID- 10885720
TI  - Disposition of a mixed meal by conscious dogs after seven days of treatment with
      cyclosporine A and prednisone.
AB  - BACKGROUND: Combination immunosuppressive therapy, that often includes prednisone
      and cyclosporine A (CyA), is commonly used in the treatment of organ transplant
      patients. We hypothesized that CyA and prednisone treatment would alter the roles
      of the liver and peripheral tissues in the disposal of carbohydrates from a meal.
      METHODS: Using the arteriovenous difference technique, we examined the
      disposition of an intragastrically delivered mixed meal in eight 24-hour fasted
      conscious dogs that had received CyA 15 mg x kg(-1) daily and prednisone 5 mg
      twice daily for 7 consecutive days before study (CyA-prednisone group). The
      results were compared with those from a group of 13 dogs (control group)
      receiving the same meal but no drugs. RESULTS: Neither arterial blood glucose
      concentrations nor arterial plasma insulin or glucagon concentrations differed
      significantly between the groups at any time. Cumulative net gut glucose output
      was equivalent to 43 +/- 9 vs 57% +/- 7% of the glucose in the meal in CyA
      prednisone vs control (p = .12). The CyA-prednisone group exhibited greater (p <
      .05) mean net hepatic glucose uptakes (15.4 +/- 4.6 vs 4.3 +/- 2.2 micromol x kg(
      1) x min(-1) and net hepatic fractional extractions of glucose (7.8 +/- 1.6 and
      1.5% +/- 1.0%) than the control group. Arterial blood lactate concentrations and
      net hepatic lactate output were greater in the CyA-prednisone group than the
      control group (p < .05). Hepatic glycogen content at the end of the study was 2.5
      fold greater in the CyA-prednisone group than in the control group (p < .05). The
      nonhepatic tissues disposed of approximately 91% of the absorbed glucose in the
      control group but only approximately 26% in the CyA-prednisone group (p < .05).
      CONCLUSIONS: CyA-prednisone treatment caused a marked shift in the carbohydrate
      disposal from a meal, enhancing the hepatic glucose uptake and decreasing
      peripheral glucose disposal.

PMID- 10885721
TI  - Indwelling catheter retraction because of pendulous breast.
AB  - Long-term home parenteral nutrition (HPN) is an established treatment for chronic
      intestinal failure. A reliable and safe vascular access is of fundamental
      importance to HPN patients. We have typically used a right atrial catheter
      attached to a subcutaneous port. We present a case of right atrial catheter
      retraction in a large-breasted woman with short bowel syndrome. The catheter was
      retracted and coiled around the reservoir in the subcutaneous pocket by motion of
      the patient with large breasts. Displacement of right atrial catheters is a rare
      but recognized complication. To avoid this complication in obese patients with
      large breasts, the positional changes of the breast should be determined. and the
      reservoir should be implanted in the area of least motion along the sternum.

PMID- 10885722
TI  - TPN and colorectal surgery.

PMID- 10885723
TI  - But interpret the evidence correctly.

PMID- 10885724
TI  - Elastin-derived protein coating onto poly(ethylene terephthalate). Technical,
      microstructural and biological studies.
AB  - Recently, it has been shown in our laboratory that certain proteins solubilized
      from elastin (ESP) formed a tight association with certain polymers such as
      elastin or polyethylene glycol terephthalate (PET) ... . The present paper deals
      with the description of the optimal chemical conditions of this unexpected
      association, its microstructure and its biological properties. A microstructural
      study of the composite ESP-PET material was performed using scanning and
      transmission electron microscopy. The thickness of the yield composite was
      evaluated (0.4-2 microm) but its imperviousness was unsatisfactory using ESP
      alone. So, we tentatively coated PET with the elastin-ESP complex. The
      microscopic views confirmed that the polymer was better filled by the organic
      matrix, the thickness of the layer being markedly improved (3 microm).
      Simultaneously, we attempted to verify whether the yielded composite retains the
      biological properties previously demonstrated with the 'Biopatches' and probably
      due to ESP. Thus, the culture of endothelial cells on an ESP-coating (with
      elastin or not) showed that a 100 microg/cm2 ESP concentration was able to
      promote endothelial cell growth in perfect conditions, maintaining their
      phenotypic character. While several physico-chemical determinations are in
      progress in our laboratory to identify and characterize the protein involved, a
      prototype of small-calibre vascular prosthesis was elaborated with elastin-ESP
      PET composite and will be placed in a dog at the abdominal femoral junction to
      evaluate the in vivo performance of such an attractive material in artery
      restoration.

PMID- 10885725
TI  - Surface reactions of a plasma-sprayed CaO-P2O5-SiO2-based glass with albumin,
      fibroblasts and granulocytes studied by XPS, fluorescence and chemiluminescence.
AB  - X-ray photoelectron spectroscopy (XPS) was used to define the chemical
      composition of the outermost surface layer and the surface modification of a
      plasma-coated phospho-silicate glass (identified as BVA) when immersed in K
      phosphate buffer or in phosphate buffered human albumin solution. Its behavior
      was compared with that of a soda-lime-based glass (identified as BVH) treated in
      the same way. The surface % composition of plasma-sprayed glass was consistent
      with bulk composition. After incubation with buffer, a Ca-P-rich layer developed
      only on the surface of BVA glass. Human serum albumin was bound reversibly to
      both glasses maintaining its native state. However, the protein completely
      covered the BVA glass surface within 24 h, with the formation of a mixed albumin
      Ca-P layer, while 4 days incubation was necessary for complete coverage of BVH
      glass surface. Murine fibroblasts seeded on plasma-coated BVA glass showed a
      proliferation pattern similar to that of control cells grown on Petri dish, while
      cells seeded on BVH had more restricted growth. A limited response was induced in
      polymorphonuclear granulocytes by both bulk glasses powder. In conclusion, the
      glass identified as BVA has the suitable characteristics of its surface layers to
      be considered biologically active from both a chemical and a cellular point of
      view.

PMID- 10885726
TI  - Peripheral nerve regeneration using silicone rubber chambers filled with
      collagen, laminin and fibronectin.
AB  - A 10 mm gap of rat sciatic nerve was created between the proximal and distal
      nerve stumps, which were sutured into silicone rubber tubes filled with an
      extracellular gel containing collagen, laminin and fibronectin. Empty silicone
      rubber tubes were used as controls. Six weeks after implantation, all
      extracellular elements were completely degraded and absorbed, and 90% of the
      animals from the extracellular gel group exhibited regeneration across the nerve
      gaps, whereas only 60% in the control group. Both qualitative and quantitative
      histology of the regenerated nerves revealed a more mature ultrastructural
      organization with 28% larger cross-sectional area and 28% higher number of
      myelinated axons in the extracellular gel group than the controls. These results
      showed that the gel mixture of collagen, laminin and fibronectin could offer a
      suitable growth medium for the regeneration of axons.

PMID- 10885727
TI  - Organotypic cultures of gingival cells: an epithelial model to assess putative
      local effects of orthodontic plate and occlusal splint materials under more
      tissue-like conditions.
AB  - This article explores whether organotypic cultures of immortalized gingival
      keratinocytes constitute a suitable model for assessing the epithelial cell
      compatibility of two groups of dental resins, each of them representing one group
      used in orthodontics and temporo-mandibular disorders (TMD) therapy under
      conditions more closely resembling the actual tissue situation. The resins were
      tested with the agar diffusion assay (ADA) in conventional monolayer and
      organotypic cultures. Compared to the control exhibiting a neutral red destaining
      index of 3, the index of 4 obtained after exposure of monolayers to one soft
      permanent resin (Durabase) indicated the presence of a non-lytic but
      physiologically active substance. In contrast, the adaptation of the ADA to
      organotypic cultures revealed no apparent lesions at the epithelial surface by
      performing scanning electron microscopy, while histoarchitecture indicated the
      development of stratified surface epithelia. This was substantiated by undamaged
      cells in the uppermost cell layers and by the preservation of cell-to-cell
      contacts. Furthermore, indirect immunofluorescence for Ki-67 and the cytokeratins
      ck 14 and ck4 revealed that cell proliferation and epithelial structure were
      maintained, while differentiation was enhanced, possibly increasing epithelial
      resistance. The results obtained from the organotypic cultures suggest that (i)
      cell-affecting effects of materials visible in monolayer cultures may not be seen
      in epithelia resembling that in vivo and that (ii) enhanced differentiation may
      be associated with increased stability of the epithelial cells. Thus, organotypic
      cultures of gingival cells constitute a tissue model allowing short-term tissue
      compatibility studies of dental materials and rendering a potential candidate
      also for long-term studies.

PMID- 10885728
TI  - Macroencapsulation of human cartilage implants: pilot study with polyelectrolyte
      complex membrane encapsulation.
AB  - Autogenous cartilage transplantation is a generally accepted method in
      reconstructive surgery. A promising alternative to this established method could
      be represented by in vitro engineering of cartilage tissue. In both methods of
      autogenous transplantation, host response induces reduction of transplant size
      and transplant instability to an unforeseeable extent. To investigate if
      polyelectrolyte complex (PEC) membranes were able to avoid host-induced effects
      on implanted tissues without neglecting the tissue metabolism, human septal
      cartilage was encapsulated with polyelectrolyte complex membranes and
      subcutaneously implanted on the back of nude mice. Septal cartilage implants,
      without encapsulation served as control group. Histochemical and electron
      microscopic investigations were performed 1, 4, 8 and 16 weeks after
      implantation. In the case of an intact PEC-membrane no interactions between the
      host and the implant could be observed. In some implants, the capsule was torn in
      several areas and signs of chronic inflammation with the cartilage having been
      affected mildly could be observed. Implanted cartilage protected with PEC
      encapsulation showed no signs of degeneration and significantly lower level of
      after effects of chronic inflammation than implanted cartilage without PEC
      encapsulation. Therefore, it could be expected, that PEC membrane encapsulation
      offers a novel approach to protect cartilage implants from host response after
      autogenous transplantation.

PMID- 10885730
TI  - Evaluation of N-succinyl-chitosan as a systemic long-circulating polymer.
AB  - The water-soluble, low toxic and less biodegradable chitosan derivative N
      succinyl-chitosan (Suc-chitosan) was investigated for body distribution and
      urinary excretion on a long-time scale (24-72 h after i.v. injection) using a
      fluorescein-labeling technique. Fluorescein isothiocyanate (FITC)-labeled Suc
      chitosan (Suc-chitosan-FTC) was characterized for molecular weight, succinylation
      degree and FTC content. Systemic retention and tissue distribution of Suc
      chitosan-FTC were examined after i.v. administration to normal and Sarcoma 180
      tumor-bearing mice. Suc-chitosan-FTC was sustained at a high level in the
      circulation over 72 h; that is, the plasma half-life in normal mice was 100.3 h
      and that in tumor-bearing mice was 43.0 h, which was longer than those of other
      long-circulating macromolecules reported to date. As to the tissues except blood
      circulation, Suc-chitosan-FTC was distributed very little in tissues other than
      the tumor. Although the total amount of Suc-chitosan-FTC residing in tested
      tissues decreased gradually, urinary excretion did not increase from 24 h after
      injection. These observations suggested that Suc-chitosan-FTC may be eliminated
      by mechanisms other than in the urine or moved to tissues other than those
      tested. The ratio of tumor accumulation reached a plateau at 48 h after
      injection, and the accumulation level, approximately 10%, was similar to those
      observed for other reported long-circulating macromolecules.

PMID- 10885729
TI  - The relative influence of the topography and chemistry of TiAl6V4 surfaces on
      osteoblastic cell behaviour.
AB  - Proliferation and adhesion of mouse (MC3T3-E1) osteoblastic cells and primary
      human osteoblastic cells were carried out on Ti6Al4V titanium alloy samples with
      varied surface roughnesses. Mechanically or manually polished surfaces were
      prepared to produce respectively non-oriented or oriented residual polishing
      grooves. Sand-blasted surfaces were prepared using 500 microm or 3 mm alumina
      particles. Surface roughness parameters showed a negative correlation in
      comparison to proliferation and adhesion parameters. X-ray microprobe chemical
      surface microanalysis showed complete disturbance of the surface element
      composition of the Ti6Al4V alloy following sand-blasting treatment. An AlOx
      enriched layer was observed on sample surfaces. This may lead to the suspicion
      that the concomittant effect of surface roughness amplitude and AlOx surface
      concentration has an effect on osteoblastic cell proliferation and adhesion.
      These findings show the significance of chemical surface analysis after any
      surface treatment of titanium-based implants before any biological use.

PMID- 10885731
TI  - Characterization of co-polymers of lactic and glycolic acid for supercritical
      fluid processing.
AB  - Polymers of lactic and glycolic acid are often used for the production of
      injectible microparticles with controlled drug release. In the variety of
      processes used for the microparticle formulation, the Aerosol Solvent Extraction
      System (ASES) is rather special. Microparticle formation and drying take place in
      one step by precipitating a methylene chloride solution of the polymer in
      supercritical CO2. This process sets special requirements to the polymers in
      crystallinity, solubility, and thermal behavior that are best fulfilled by
      blocked copolymers. This study investigates a number of lactide-co-glycolide
      polymers with blocked distribution of the co-monomers by NMR spectroscopy and
      powder diffraction. The molar ratios are determined by 1H-NMR spectroscopy to
      verify the manufacturer's declarations of the purchased specimens. Additionally,
      the block length is determined by application of 13C-NMR. Therefore, a method
      reported in the literature was modified and evaluated in order to calculate the
      length of lactide and glycolide sequences in the polymer. Furthermore, this study
      looks at the impact of synthesis conditions on block length and crystallinity,
      and the impact of the blocking on both, crystallinity and solubility of the
      polymers.

PMID- 10885732
TI  - In vitro degradation of porous poly(L-lactic acid) foams.
AB  - This study investigated the in vitro degradation of porous poly(L-lactic acid)
      (PLLA) foams during a 46-week period in pH 7.4 phosphate-buffered saline at 37
      degrees C. Four types of PLLA foams were fabricated using a solvent-casting,
      particulate-leaching technique. The three types had initial salt weight fraction
      of 70, 80, and 90%, and a salt particle size of 106-150 microm, while the fourth
      type had 90% initial weight fraction of salt in the size range 0-53 microm. The
      porosities of the resulting foams were 0.67, 0.79, 0.91, and 0.84, respectively.
      The corresponding median pore diameters were 33, 52, 91, and 34 microm. The
      macroscopic degradation of PLLA foams was independent of pore morphology with
      insignificant variation in foam weight, thickness, pore distribution, compressive
      creep behavior, and morphology during degradation. However, decrease in melting
      temperature and slight increase in crystallinity were observed at the end of
      degradation. The foam half-lives based on the weight average molecular weight
      were 11.6+/-0.7 (70%, 106-150 microm), 15.8+/-1.2 (80%, 106-150 microm), 21.5+/
      1.5 (90%, 106-150 microm), and 43.0+/-2.7 (90%, 0-53 microm) weeks. The thicker
      pore walls of foams prepared with 70 or 80% salt weight fraction as compared to
      those with 90% salt weight fraction contributed to an autocatalytic effect
      resulting in faster foam degradation. Also, the increased pore surface/volume
      ratio of foams prepared with salt in the range 0-53 microm enhanced the release
      of degradation products thus diminishing the autocatalytic effect and resulting
      in slower foam degradation compared to those with salt in the range 106-150
      microm. Formation and release of crystalline PLLA particulates occurred for foams
      fabricated with 90% salt weight fraction at early stages of degradation. These
      results suggest that the degradation rate of porous foams can be engineered by
      varying the pore wall thickness and pore surface/volume ratio.

PMID- 10885733
TI  - Tendon cell contraction of collagen-GAG matrices in vitro: effect of cross
      linking.
AB  - The contraction of connective tissue cells can play important roles in wound
      healing and pathological contractures. The effects of this contractile behavior
      on cell-seeded constructs for tissue engineering have not yet been investigated.
      The goal of this work was to investigate in vitro tendon cell-mediated
      contraction of collagen-glycosaminoglycan (GAG) matrices cross-linked using
      selected methods. Highly porous collagen-GAG sponges were seeded with calf tendon
      cells and the projected area and DNA content of the sponges measured at 3, 7, 14,
      and 21 days post-seeding. Immunohistochemistry was performed to determine if
      alpha-smooth muscle actin (SMA) was associated with the cell contraction of the
      matrices. Dehydrothermal (DHT) treatment alone was not sufficient to resist
      contraction by the seeded tendon fibroblasts. Cross-linking of the collagen-GAG
      sponges to the extent that the modulus was three times that of sponges treated by
      DHT alone was necessary to resist contraction. SMA was seen in the cytoplasm of
      most cells in all sponges at all time periods. The results provide a rational
      basis for the determination of the mechanical properties of collagen matrices
      required for engineering certain connective tissues.

PMID- 10885734
TI  - Catastrophic epilepsy in childhood.
AB  - Although for most children epilepsy is a relatively benign disorder, for some,
      epilepsy can be designated as "catastrophic" because the seizures are so
      difficult to control and because they are strongly associated with mental
      retardation. The catastrophic childhood epilepsies include uncommon disorders
      such as early infantile epileptic encephalopathy with suppression burst, severe
      myoclonic epilepsy of infancy, and epilepsy with myoclonic-astatic seizures.
      There are other syndromes that are relatively common such as infantile spasms,
      Lennox-Gastaut syndrome, and Sturge-Weber syndrome. Many children with
      catastrophic epilepsy have the seizures as a result of underlying brain
      abnormalities that will inevitably lead to mental retardation whether or not they
      have seizures. In some patients, however, the mental retardation appears to be
      caused by the seizures. Developmental plasticity provides children with an
      opportunity to recover from significant brain injuries. However, the plasticity
      may also be the cause of the mental retardation. In such patients, control of the
      seizures may lead to more normal intellectual development. Thus, every effort
      should be made to control seizures in children with catastrophic epilepsy.

PMID- 10885735
TI  - Sudden unexplained death and injury in epilepsy.
AB  - Seizures may be associated with risk of injury or death. Injuries are common in
      patients with epilepsy, with up to 30% of patients reporting injuries, most
      commonly blunt trauma and lacerations. Seizures associated with falls increase
      the risk of injury, but any seizure that is associated with alteration in
      consciousness may cause injury. Patients with seizures may injure others,
      especially by causing motor vehicle accidents. Each state has restrictions on
      driving, requiring seizure-free intervals that range from 3 to 18 months.
      Mortality is increased in patients with epilepsy. The standardized mortality
      ratio is increased two to three times in epilepsy cohorts. Sudden unexplained
      death in epilepsy (SUDEP) is responsible for 2% to 17% of all deaths in patients
      with epilepsy, depending on the cohort studied. Population-based studies of SUDEP
      show a lower overall SUDEP rate compared with clinical trials or epilepsy
      referral center cohorts. Overall, the risk of sudden death is increased in the
      epilepsy population by 24 times compared with the general population. Risk
      factors for SUDEP may include poorly controlled seizures, early onset of
      epilepsy, and generalized tonic-clonic seizures. The pathophysiology of SUDEP is
      unknown, but animal data suggest apnea may be the initial factor that results in
      sudden death.

PMID- 10885736
TI  - Is epilepsy a progressive disease? The neurobiological consequences of epilepsy.
AB  - While primary, or idiopathic, epilepsies may exist, in the vast majority of cases
      epilepsy is a symptom of an underlying brain disease or injury. In these cases,
      it is difficult if not impossible to dissociate the consequences of epilepsy from
      the consequences of the underlying disease, the treatment of either the disease
      or the epilepsy, or the actual seizures themselves. Several cases of apparent
      complications of epilepsy are presented to illustrate the range of consequences
      encountered in clinical practice and the difficulty in assigning blame for
      progressive symptomatology in individual cases. Because of the difficulty in
      interpreting clinical material, many investigators have turned to epilepsy models
      in order to address the potential progressive consequences of recurrent seizures.
      The authors review experimental data, mainly from animal models, that illustrate
      short-, medium-, and long-term morphological and biochemical changes in the brain
      occurring after seizures, and attempt to relate these observations to the human
      condition.

PMID- 10885737
TI  - Status epilepticus: risk factors and complications.
AB  - Status epilepticus is common and associated with significant mortality and
      complications. It affects approximately 50 patients per 100,000 population
      annually and recurs in >13%. History of epilepsy is the strongest single risk
      factor for generalized convulsive status epilepticus. More than 15% of patients
      with epilepsy have at least one episode of status epilepticus and low
      antiepileptic drug levels are a potentially modifiable risk factor. Other risks
      include young age, genetic predisposition, and acquired brain insults. Fever is a
      very common risk in children, as is stroke in adults. Mortality rates are 15% to
      20% in adults and 3% to 15% in children. Acute complications result from
      hyperthermia, pulmonary edema, cardiac arrhythmias, and cardiovascular collapse.
      Long-term complications include epilepsy (20% to 40%), encephalopathy (6% to
      15%), and focal neurologic deficits (9% to 11%). Neuronal injury leading to
      temporal lobe epilepsy is probably mediated by excess excitation via activation
      of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors and consequent
      elevated intracellular calcium that causes acute necrosis and delayed apoptotic
      cell death. Some forms of nonconvulsive status epilepticus may also lead to
      neuronal injury by this mechanism, but others may not. Based on clinical and
      experimental observations, complex partial status epilepticus is more likely to
      result in neuronal injury similar to generalized convulsive status epilepticus.
      Absence status epilepticus is much less likely to result in neuronal injury, and
      complications because it may be mediated primarily through excess inhibition.
      Future research strategies to prevent complications of status epilepticus include
      the study of new drugs (including NMDA antagonists, new drug delivery systems,
      and drug combinations) to stop seizure activity and prevent acute and delayed
      neuronal injury that leads to the development of epilepsy.

PMID- 10885738
TI  - Psychiatric comorbidity in chronic epilepsy: identification, consequences, and
      treatment of major depression.
AB  - The purpose of this article is to review the topic of interictal psychiatric
      comorbidity among adult patients with chronic epilepsy, focusing specifically on
      those studies that have used contemporary psychiatric nosology. Five specific
      issues are addressed: (a) the risk and predominant type(s) of psychiatric
      comorbidity in chronic epilepsy, (b) adequacy of recognition and treatment of
      psychiatric comorbidity, (c) the additional burdens that comorbid psychiatric
      disorders impose upon patients with chronic epilepsy, (d) the etiology of these
      disorders, and (e) strategies for treatment. Current appreciation for these
      issues in epilepsy is contrasted to related fields (e.g., primary care,
      psychiatry, and epidemiology), where considerable attention has been devoted to
      the identification, consequences, and treatment of psychiatric comorbidity. The
      issue of psychiatric comorbidity in epilepsy is reviewed with the aim of
      identifying a clinical and research agenda that will advance understanding of at
      least one important psychiatric condition associated with epilepsy-namely, major
      depression.

PMID- 10885739
TI  - Adverse effects of antiepileptic drugs.
AB  - Because the efficacies of antiepileptic drugs (AEDs) are often equivalent,
      selection of an AED is often determined by adverse effects. Differences in
      methods for labeling adverse effects and in the adverse effect terms themselves,
      variations in the populations studied, and inconsistent classifications of
      adverse effects make it difficult to know how to use information on adverse
      effects to choose an AED. Effort is underway to develop more extensive and
      internationally acceptable descriptive terms for adverse effects. Comparison of
      adverse effects in patients taking AEDs with adverse events in control groups is
      helpful; however, data from controlled studies are often lacking for most AEDs.
      Because of these limitations, the clinician must adopt a preventative and early
      detection approach based on some general principles. This review outlines factors
      to consider for avoiding and detecting AED adverse effects. The occurrence of
      weight change with AEDs is reviewed extensively, serving to illustrate how the
      principle factors can be used to avoid and manage adverse effects and where there
      is need for better studies of the short- and long-term adverse effects of AEDs.

PMID- 10885740
TI  - The effects of epilepsy and its treatment on sexual and reproductive function.
AB  - Male and female sexuality and reproductive functions are complex systems with
      cortical, limbic system, hypothalamic, pituitary, and end organ interactions.
      Sexual steroids are produced in the sexual glands, the adrenals, and the brain.
      They undergo interconversion in the brain, bind to different brain areas, and
      have multiple effects behaviorally and neurophysiologically. Progesterone,
      estrogen and testosterone have neuroendocrine effects that alter
      epileptogenicity. Seizure frequency may change throughout the life cycle as a
      result of hormonal status. Changes in central control, peripheral hormone levels,
      and/or medication effects may all contribute to decreased libido, potency, and
      fertility. Antiepileptic drugs (AEDs) interact with hormone-binding metabolism,
      resulting in altered human reproductive function. AEDs alter contraceptive
      hormone treatments. Information on the effects of new AEDs is being gathered by
      the National Pregnancy Registry. Catamenial epilepsy and some sexual dysfunction
      in men may be treatable.

PMID- 10885741
TI  - Cost evaluations in epilepsy: an update.
AB  - The purpose of this article is to describe the developments in the methodology of
      studies of the cost of epilepsy and cost-effectiveness of treatments in light of
      previous reviews and recently published methodological guidelines. Several recent
      studies are compared, with recently published guidelines by the US Public Health
      Service (PHS) serving as a framework for discussing selected methodological
      issues. Results show that these recent studies have made important gains in the
      quality of cost data obtained, with advances being made by studies that base cost
      estimates on actual patient data from representative samples as opposed to
      secondary sources and expert opinions. However, a wide variety of methods
      continue to be used for many aspects of study design and reporting. Method
      heterogeneity remains an obstacle to presenting and interpreting reliable and
      valid information on costs and cost-effectiveness. Areas in need of additional
      development are methods for estimating direct nonmedical costs, attributing costs
      to epilepsy versus comorbid conditions, validating health state valuation methods
      for this population, and validating current recommendations for capturing the
      costs of lost productivity due to epilepsy. PHS panel recommendations provide a
      useful framework for working toward consistency in the methods for economic
      studies in epilepsy.

PMID- 10885742
TI  - Activin receptor-like kinase 2 can mediate atrioventricular cushion
      transformation.
AB  - Epithelial-mesenchymal transformation in the atrioventricular (AV) cushion of the
      tubular heart is a critical step in the formation of the valves and membranous
      septa. Transforming growth factor beta (TGFbeta) ligands are a primary signal of
      this transformation. To investigate the expression and function of specific Type
      I TGFbeta receptors during AV cushion transformation, we cloned and characterized
      the chicken homologues of two mammalian activin receptor-like kinases (ALK), ALK2
      and ALK5, and generated specific, polyclonal antibodies against the extracellular
      binding domains of each. Both the chicken ALK2 (ChALK2) and the chicken ALK5
      (ChALK5) cDNAs encode proteins that bind TGFbeta1 in the presence of the Type II
      TGFbeta receptor. However, as expected, only ChALK5 stimulated the TGFbeta
      responsive PAI-1 promoter. These data establish that ChALK2 and ChALK5 are the
      chicken homologues of the mammalian receptors ALK2 and ALK5. Both ChALK2 and
      ChALK5 are expressed by AV endocardial cells. AV cushion explants harvested from
      stage 13-18 embryos were incubated with antisera to ChALK2 or ChALK5. Anti-ChALK2
      antisera inhibited mesenchyme formation by 34-50% while neutralizing anti-ChALK5
      antisera were without effect. These data demonstrate that ChALK2 can mediate
      transformation in the AV cushion.

PMID- 10885743
TI  - Locally released retinoic acid repatterns the first branchial arch cartilages in
      vivo.
AB  - The fates of cranial neural crest cells are unique compared to trunk neural
      crest. Cranial neural crest cells form bone and cartilage and ultimately these
      cells make up the entire facial skeleton. Previous studies had established that
      exogenous retinoic acid has effects on neurogenic derivatives of cranial neural
      crest cells and on segmentation of the hindbrain. In the present study we
      investigated the role of retinoic acid on the skeletal derivatives of migrating
      cranial neural crest cells. We wanted to test whether low doses of locally
      applied retinoic acid could respecify the neural crest-derived, skeletal
      components of the beak in a reproducible manner. Retinoic acid-soaked beads were
      positioned at the presumptive mid-hindbrain junction in stage 9 chicken embryos.
      Two ectopic cartilage elements were induced, the first a sheet of cartilage
      ventral and lateral to the quadrate and the second an accessory cartilage rod
      branching from Meckel's cartilage. The accessory rod resembled a retroarticular
      process that had formed within the first branchial arch domain. In addition the
      quadrate was often displaced laterally and fused to the retroarticular process.
      The next day following bead implantation, expression domains of Hoxa2 and Hoxb1
      were shifted in an anterior direction up to the mesencephalon and Msx-2 was
      slightly down-regulated in the hindbrain. Despite down-regulation in neural crest
      cells, the onset of Msx-2 expression in the facial prominences at stage 18-20 was
      normal. This correlates with normal distal beak morphology. Focal labeling of
      neural crest with DiI showed that instead of migrating in a neat group toward the
      second branchial arch, a cohort of labeled cells from r4 spread anteriorly toward
      the proximal first arch region. AP-2 expression data confirmed the uninterrupted
      presence of AP-2-expressing cells from the anterior mesencephalon to r4. The
      morphological changes can be explained by mismigration of r4 neural crest into
      the first arch, but at the same time maintenance of their identity. Up-regulation
      of the Hoxa2 gene in the first branchial arch may have encouraged r4 cells to
      move in the anterior direction. This combination of events leads to the first
      branchial arch assuming some of the characteristics of the second branchial arch.

PMID- 10885744
TI  - Essential functions of DNA topoisomerase I in Drosophila melanogaster.
AB  - DNA topoisomerase I (topo I) is an essential enzyme involved in replication,
      transcription, and recombination. To probe the functions of topo I during
      Drosophila development, we used top1-deficient flies with heat-shock-inducible
      top1 transgenes and were able to observe both zygotic and maternal functions of
      top1. A critical period for the zygotic function is in the late larval and early
      pupal stages. Topo I is required for larval growth and cell proliferation in
      imaginal disc tissues. The maternal functions consist of two aspects: oogenesis
      and early embryogenesis. During oogenesis, topo I is detected in the nuclei of
      early germ-line cells and follicle cells. The mutant ovary exhibits abnormal
      proliferation and defective nuclear morphology in these cells. There are
      extranumeral germ-line cells in individual egg chambers, while the follicle cells
      are underreplicated. Topo I is also stored maternally in early embryos. It
      localizes to the nuclei during interphase and prophase, but disperses into the
      cytoplasm at metaphase. Embryos from the mutant mother frequently show disrupted
      nuclear divisions with defects in chromosome condensation and segregation. The
      cytological and genetic analysis of the top1 mutant demonstrates that in
      Drosophila, topo I plays critical roles in many developmental stages active in
      cell proliferation.

PMID- 10885747
TI  - A large targeted deletion of Hoxb1-Hoxb9 produces a series of single-segment
      anterior homeotic transformations.
AB  - Hox genes regulate axial regional specification during animal embryonic
      development and are grouped into four clusters. The mouse HoxB cluster contains
      10 genes, Hoxb1 to Hoxb9 and Hoxb13, which are transcribed in the same direction.
      We have generated a mouse strain with a targeted 90-kb deletion within the HoxB
      cluster from Hoxb1 to Hoxb9. Surprisingly, heterozygous mice show no detectable
      abnormalities. Homozygous mutant embryos survive to term and exhibit an ordered
      series of one-segment anterior homeotic transformations along the cervical and
      thoracic vertebral column and defects in sternum morphogenesis. Neurofilament
      staining indicates abnormalities in the IXth cranial nerve. Notably, simultaneous
      deletion of Hoxb1 to Hoxb9 resulted in the sum of phenotypes of single HoxB gene
      mutants. Although a higher penetrance is observed, no synergistic or new
      phenotypes were observed, except for the loss of ventral curvature at the
      cervicothoracic boundary of the vertebral column. Although Hoxb13, the most 5'
      gene, is separated from the rest by 70 kb, it has been suggested to be expressed
      with temporal and spatial colinearity. Here, we show that the expression pattern
      of Hoxb13 is not affected by the targeted deletion of the other 9 genes. Thus,
      Hoxb13 expression seems to be independent of the deleted region, suggesting that
      its expression pattern could be achieved independent of the colinear pattern of
      the cluster or by a regulatory element located 5' of Hoxb9.

PMID- 10885748
TI  - Periodic increases in elongation rate precede increases in cytosolic Ca2+ during
      pollen tube growth.
AB  - Pollen tubes grown in vitro require an intracellular tip-high gradient of Ca2+ in
      order to elongate. Moreover, after about 2 h in vitro both the tip Ca2+ and the
      elongation rate of lily tubes begin to oscillate regularly with large amplitudes.
      This raises the question of the phase relation between these two oscillations.
      Previous studies lacked the temporal resolution to accurately establish this
      relationship. We have studied these oscillations with a newly developed, high
      temporal resolution system and the complementary use of both luminescent and
      fluorescent calcium reporters. We hereby show that the periodic increases in
      elongation rate during oscillatory growth of Lilium longiflorum pollen tubes
      clearly precede those in subtip calcium and do so by 4.1 +/- 0.2 s out of average
      periods of 38.7 +/- 1.8 s. Also, by collecting images of the light output of
      aequorin, we find that the magnitude of the [Ca2+] at the tip oscillates between
      3 and 10 microM, which is considerably greater than that reported by fluorescent
      indicators. We propose an explanatory model that features cyclic growth and
      secretion in which growth oscillations give rise to secretion that is essential
      for the subsequent growth oscillation. We also critically compile data on L.
      longiflorum stylar growth rates, which show little variation from in vitro rates
      of pollen tubes grown in optimal medium.

PMID- 10885746
TI  - The spd-2 gene is required for polarization of the anteroposterior axis and
      formation of the sperm asters in the Caenorhabditis elegans zygote.
AB  - In the Caenorhabditis elegans zygote, polarization of the anteroposterior (AP)
      axis occurs during a brief period of reorganization that follows fertilization
      and results in the establishment of discrete cytoplasmic and cortical domains. In
      the cytoplasm, germ-line or P granules are circulated by an actomyosin-driven
      fountain flow of cytoplasm and localize to the posterior, while in the cortex,
      two proteins required for AP polarity, PAR-2 and PAR-3, localize to the posterior
      and the anterior, respectively. The identity of the positional cue that
      determines AP axis orientation is not known, although it has been postulated to
      be a component of the sperm pronucleus/centrosome complex (SPCC) as the position
      of the SPCC correlates with the orientation of the AP axis and the direction of
      the fountain flows. Here, we show that mutations in the spd-2 gene disrupt
      polarization of the AP axis. In mutant zygotes, the fountain flow of cytoplasm
      and associated asymmetric cortical contractions are absent, P granules do not
      localize, and cortical PAR-3 does not become asymmetrically distributed.
      Interestingly, cortical PAR-2 localizes randomly to either or both poles. The
      random positioning of PAR-2 requires PAR-3 and indicates that a spd-2-dependent
      mechanism normally modulates PAR-2/PAR-3 interactions to correctly position PAR-2
      at the posterior. spd-2 mutations also disrupt formation of the SPCC by delaying
      and attenuating the formation of sperm asters until after the period of
      reorganization, suggesting that spd-2 mutations disrupt formation of the
      positional cue. Our results also indicate that sperm asters are not essential for
      pronuclear migration but are required for rapid female pronuclear movement and
      premitotic positioning of the pronuclei.

PMID- 10885745
TI  - Pax-6 expression and activity are induced in the reepithelializing cornea and
      control activity of the transcriptional promoter for matrix metalloproteinase
      gelatinase B.
AB  - Recent evidence supports the idea that matrix metalloproteinases (MMPs) act as
      morphogenetic regulators in embryonic and adult events of tissue remodeling. MMP
      activity is controlled primarily at the level of gene expression. In a recent
      study we characterized the transcriptional promoter of the MMP gene, gelatinase B
      (gelB), in transgenic mice, demonstrating the requirement for DNA sequences
      between -522 and +19 for appropriate activity. In this study we investigated
      factors required for gelB promoter activity in the developing eye and
      reepithelializing adult cornea. Pax-6 is a homeobox and paired domain
      transcription factor that acts at the top of the hierarchy of genes controlling
      eye development. Pax-6 is also expressed in the adult eye. We show here that the
      tissue expression pattern of Pax-6 overlaps extensively with gelB promoter
      activity in the developing and adult eye. In addition Pax-6 is observed to be
      upregulated in repairing corneal epithelium, as is gelB promoter activity. In
      cell culture transfection experiments, we identified two promoter regions which
      mediate positive response to Pax-6. By electrophoretic mobility shift assay, we
      further pinpoint two Pax-6 binding sites within these response regions and
      demonstrate direct interaction of the Pax-6 paired domain with one of these
      sites. These data suggest a mechanism by which Pax-6 may direct gelB expression
      in an eye-specific manner.

PMID- 10885749
TI  - Zona pellucida protein binding ability of porcine sperm during epididymal
      maturation and the acrosome reaction.
AB  - In many mammals, the first interaction between gametes during fertilization
      occurs when sperm contact the zona pellucida surrounding the egg. Although
      porcine sperm first contact the zona pellucida via their plasma membrane, the
      regions of the sperm surface that display zona receptors have not been
      determined. We have used the Alexa 488 fluorophore conjugated to solubilized
      porcine zona pellucida proteins to observe zona receptors on live boar sperm.
      Zona proteins bound live, acrosome-intact sperm on the anterior portion of the
      sperm head, concentrated in a thin band over the acrosomal ridge. When sperm
      membranes were permeabilized by fixation or acrosome reactions induced by the
      ionophore A23187, zona binding was extended to a broad area covering the entire
      acrosomal region. Zona binding proteins were present in the acrosomes of sperm
      from all regions of the epididymis. In contrast, zona binding sites were found on
      the plasma membrane of most sperm from the corpus and cauda epididymis, but on
      only 6% of caput epididymal sperm. In conclusion, acrosome-intact boar sperm
      exhibit concentrated zona protein binding over the acrosomal ridge and acquire
      this binding in the corpus region of the epididymis, correlating with the
      developmental stage at which sperm gain the ability to fertilize oocytes.

PMID- 10885750
TI  - Microphthalmia due to p53-mediated apoptosis of anterior lens epithelial cells in
      mice lacking the CREB-2 transcription factor.
AB  - CREB-2 (also called ATF4, TAXREB67, or C/ATF) is an evolutionarily conserved
      member of the CREB/ATF family of basic-leucine zipper transcription factors. CREB
      2 is expressed ubiquitously in the adult mouse and can function as both a
      transcriptional activator and a repressor. However, little was understood about
      the normal function of CREB-2 in mammalian development or organ physiology. In
      this report we have used gene targeting to produce CREB-2-deficient (CREB-2-/-)
      mice. Adult CREB-2-/- mice displayed microphthalmia due to the complete absence
      of a lens. Early embryonic lens development including formation of the optic
      vesicle, primary lens fibers, and proliferating anterior epithelial cells
      occurred normally in these mice. However, beginning at ED 14.5 the CREB-2
      deficient anterior epithelial lens cells underwent massive and synchronous
      apoptosis. This was followed by the complete resorption of the developing lens.
      Consistent with this defect in anterior epithelial cell survival, in situ
      hybridization studies showed that CREB-2 is expressed at high levels in wild-type
      anterior epithelial lens cells at ED 14.5. The defect in lens formation seen in
      the CREB-2-/- mice was not associated with qualitative defects in the expression
      of Pax-6, alphaA-crystallin, c-maf, or PDGF-R alpha. However, apoptosis of the
      anterior epithelial cells was mediated by a p53-dependent cell death pathway
      because ablation of the p53 gene rescued anterior epithelial cell death and
      allowed the formation of a lens in the absence of CREB-2. Taken together, these
      results identify CREB-2 as an important regulator of mammalian lens development.

PMID- 10885751
TI  - Beta-catenin signaling activity dissected in the early Xenopus embryo: a novel
      antisense approach.
AB  - Xenopus embryos develop dorsal/ventral and anterior/posterior axes as a result of
      the activity of a maternal Xwnt pathway, in which beta-catenin is an essential
      component, acting as a transactivator of transcription of zygotic genes. However,
      the questions of where and when beta-catenin is required in early embryogenesis
      have not been addressed directly, because no loss-of-function method has been
      available. Here we report the use of a novel antisense approach that allows us to
      target depletion of protein to individual blastomeres. When a "morpholino" oligo
      complementary to beta-catenin mRNA is injected into early embryos, it depletes
      beta-catenin protein effectively through the neurula stage. By targeting the
      oligo to different cleavage blastomeres, we block beta-catenin activity in
      different areas and at different times. Dorsal vegetal injection at the 2- and 4
      cell stages blocks dorsal axis formation and at the 8-cell stage blocks head
      formation, while A-tier injection at the 32-cell stage causes abnormal cement
      gland formation. This approach shows the complex involvement of Xwnt pathways in
      embryonic patterning and offers a rapid method for the functional analysis of
      both maternal and early zygotic gene products in Xenopus.

PMID- 10885752
TI  - Combinatorial activity of pair-rule proteins on the Drosophila gooseberry early
      enhancer.
AB  - The early expression of the Drosophila segment polarity gene gooseberry (gsb) is
      under the control of the pair-rule genes. We have identified a 514-bp enhancer
      which reproduces the early gsb expression pattern in transgenic flies. The
      transcription factor Paired (Prd) is the main activator of this enhancer in all
      parasegments of the embryo. It binds to paired- and homeodomain-binding sites,
      which are segregated on the enhancer. Using site-directed mutagenesis, we have
      identified sites critical for Prd activity. Negative regulation of this enhancer
      is mediated by the Even-skipped protein (Eve) in the odd-numbered parasegments
      and by the combination of Fushi-tarazu (Ftz) and Odd-skipped proteins in the even
      numbered parasegments. The organisation of the Prd-binding sites, as well as the
      necessity for intact DNA binding sites for both paired- and homeodomains,
      suggests a molecular model whereby the two DNA-binding domains of the Prd protein
      cooperate in transcriptional activation of gsb. This positive activity appears to
      be in competition with Eve and Ftz on Prd homeodomain-binding sites.

PMID- 10885753
TI  - The zebrafish floating head mutant demonstrates podocytes play an important role
      in directing glomerular differentiation.
AB  - In zebrafish, the pronephric glomerulus occupies a midline position underneath
      the notochord and is vascularized through angiogenic capillary ingrowth from the
      dorsal aorta. The midline mutants floating head (flh), sonic you (syu), and you
      too (yot) provide the opportunity to study glomerular differentiation in the
      absence of the notochord and vascularization from the dorsal aorta. In flh, syu,
      and yot mutants, glomeruli differentiate at ectopic lateral positions within the
      embryo and contain morphologically identifiable podocyte and endothelial cell
      types. In the absence of the dorsal aorta, endothelia from an alternate source
      are recruited by podocytes during glomerular vascularization to make functional
      glomeruli. Our results suggest that midline signals are required for proper
      glomerular morphogenesis but not for the differentiation of podocytes. Podocytes
      appear to play an important role in directing cellular recruitment events leading
      to glomerular differentiation. Furthermore, we find defects in sclerotomal
      development that correlate with defects in glomerular morphogenesis suggesting a
      possible link between the formation of these embryonic structures.

PMID- 10885754
TI  - cDNA subtraction cloning reveals novel genes whose temporal and spatial
      expression indicates association with trophoblast invasion.
AB  - Trophoblast invasion is a critical process in development of most mammals that
      shares similarities with the invasive behavior of tumor cells. In the present
      investigation, a cDNA subtraction library was constructed between invasive
      trophoblast at day 8 of murine development and mature noninvasive placenta at day
      18 of gestation. One of the differentially expressed clones, Epcs26, was mapped
      to the X chromosome and revealed no homology to any known gene. It was
      predominantly expressed in parietal endoderm, undifferentiated cells of the
      ectoplacental cone, and a few trophoblast giant cells. Another gene, designated
      Epcs50, was mapped to chromosome 19. It exhibited homologies to the mouse Mps1
      gene and, like Mps1, may have a distant relationship to the lytic protein
      perforin. High expression was detected in parietal endoderm cells and in a subset
      of secondary trophoblast giant cells. Two sequences, Epcs24 and Epcs68, exhibited
      an extensive open reading frame that shared the common features of the cysteine
      proteinase cathepsin L. Expression was confined to an undefined subpopulation of
      trophoblast giant cells. Both genes were mapped to chromosome 13 in close
      proximity to cathepsins L and J. The known functions of MPS1 and cathepsin L
      proteins indicate that the related proteins EPCS50, EPCS24, and EPCS68
      participate in conferring invasive properties to the mouse trophoblast.

PMID- 10885755
TI  - Overexpression of FGF-2 alters cell fate specification in the developing retina
      of Xenopus laevis.
AB  - The developing vertebrate retina produces appropriate ratios of seven
      phenotypically and functionally distinct cell types. Retinal progenitors remain
      multipotent up until the last cell division, favoring the idea that extrinsic
      cues direct cell fate. We demonstrated previously that fibroblast growth factor
      (FGF) receptors are necessary for transduction of signals in the developing
      Xenopus retina that bias cell fate decisions (S. McFarlane et al., 1998,
      Development 125, 3967-3975). However, the precise identity of the signal remains
      unknown. To test whether an FGF signal is sufficient to influence cell fate
      choices in the developing retina, FGF-2 was overexpressed in Xenopus retinal
      precursors by injecting, at the embryonic 16-cell stage, a cDNA plasmid encoding
      FGF-2 into cells fated to form the retina. We found that FGF-2 overexpression in
      retinal precursors altered the relative numbers of transgene-expressing retinal
      ganglion cells (RGC) and Muller glia; RGCs were increased by 35% and Muller glia
      decreased by 50%. In contrast, the proportion of retinal precursors that became
      photoreceptors was unchanged. Within the photoreceptor population, however, we
      found a twofold increase in rod photoreceptors at the expense of cone
      photoreceptors. These data are consistent with an endogenous FGF signal
      influencing cell fate decisions in the developing vertebrate retina.

PMID- 10885757
TI  - AIDS 1999. Virology: overview.

PMID- 10885756
TI  - Cell-substrate interactions during sea urchin gastrulation: migrating primary
      mesenchyme cells interact with and align extracellular matrix fibers that contain
      ECM3, a molecule with NG2-like and multiple calcium-binding domains.
AB  - The migratory primary mesenchyme cells (PMCs) of the sea urchin embryo are a
      model experimental system for the analysis of cell-extracellular matrix (ECM)
      interactions. Although the behavior of PMCs during gastrulation has been analyzed
      in considerable detail, it has proven difficult to identify specific substrate
      molecules with which these cells interact. Here, using a new monoclonal antibody
      (2.5C4) generated by an in vitro immunization procedure, we show that migrating
      PMCs interact with a distinct class of ECM fiber. The 2.5C4-positive fibers are
      distributed in a vegetal (high) to animal (low) gradient on the basal surface of
      the ectoderm. Three observations indicate that PMC filopodia interact directly
      with the fibers: (1) During gastrulation, 2.5C4-positive fibers gradually become
      oriented in a prominent circumferential belt that corresponds precisely to the
      position of the subequatorial PMC ring. (2) This fiber pattern is blocked by
      microsurgical removal of PMCs but is restored if PMCs are reintroduced into the
      embryo. (3) Examination of immunostained embryo whole mounts by confocal
      microscopy reveals a striking association between PMC filopodial roots and foci
      of fiber bundling. Double-immunostaining experiments using 2.5C4 and antibodies
      against previously identified matrix constituents show that the protein ECM3 is a
      component of the fibers. We have determined the complete amino acid sequence of
      ECM3 and find that this large protein (3103 amino acids) consists of an N
      terminal domain similar to the mammalian chondroitin sulfate proteoglycan core
      protein NG2, a central region composed of five tandem repeats of a domain
      contained within the regulatory Ca2+-binding loop of Na+-Ca2+ exchange proteins,
      and a C-terminal region with no homology to known proteins. The general structure
      of ECM3 is similar in several respects to that of a sponge protein, MAFp4. MAFp4
      is a major component of aggregation factor, an ECM complex that mediates the
      calcium-dependent, species-specific sorting of sponge cells. These studies
      establish ECM3 as a strong candidate for a PMC substrate molecule and point to
      several possible mechanisms by which interactions between PMC filopodia and ECM3
      containing fibers could provide guidance information to migrating PMCs.

PMID- 10885758
TI  - Murine models for HIV disease.

PMID- 10885759
TI  - Molecular interactions of HIV with host factors.

PMID- 10885760
TI  - Immune reconstitution in HIV infection.
AB  - The weight of the published evidence suggest that there is clinically significant
      immune recovery in a sizable fraction of HIV-infected patients who achieve
      suppression of viral replication. At the same time, it is clear that very few
      patients regain normal (i.e. equivalent to pre-infection) immune function, at
      least after the follow-up periods available so far. The experience from bone
      marrow transplantation or intensive chemotherapy in adults suggests that such
      kind of immune reconstitution is unlikely (at least with treatments limited to
      stopping virus replication) once the immune system has been sufficiently damaged.
      It is also clear that effective immunity to HIV is not achieved in a significant
      proportion of patients. These findings have implications for both basic research
      and clinical practice. From the laboratory perspective, besides the urgent need
      to characterize the protective immunity to HIV (if it exists), it would be
      desirable to find some simple measure of the immune function of patients who
      receive therapy. The combination of markers of immune activation together with
      CD4 cell count and viral load should be further evaluated in this context.
      Regarding clinical practice, it is likely that prophylaxes for opportunistic
      infections can be discontinued uneventfully in the majority of patients
      responding to HAART. Although the evidence is not yet conclusive, all available
      data suggest this will be the case. Given that there is significant immune
      reconstitution even in advanced disease, it is tempting to consider if this fact
      can be used to support antiviral therapy recommendations that are less aggressive
      than the current ones. HIV eradication by pharmacologic means alone does not seem
      possible yet, and no effective immune response to HIV seems to be generated by
      starting therapy in the asymptomatic (as opposed to acute infection) stage of the
      disease. At the same time, the follow-up studies on prolonged antiretroviral
      therapy suggest that virologic failure will take place despite many months of
      seemingly adequate suppression. This fact, taken together with the side effects
      and inconvience of current antiretroviral regimens, can be used to support an
      argument in favor of evaluating strategies to treat later rather than earlier.

PMID- 10885761
TI  - Advances in understanding the evolution of HIV.

PMID- 10885763
TI  - AIDS 1999. Epidemiology: overview.

PMID- 10885762
TI  - Latency and reservoirs for HIV-1.

PMID- 10885764
TI  - Changes in HIV and AIDS epidemiology from new generation antiretroviral therapy.

PMID- 10885765
TI  - Towards a better understanding of the epidemiology of HIV-2.

PMID- 10885766
TI  - Microbicides and barrier methods in HIV prevention.

PMID- 10885767
TI  - Interventions to reduce mother-to-child transmission of HIV infection: new
      developments and current controversies.

PMID- 10885768
TI  - AIDS 1999. Vaccines and immunology: overview.

PMID- 10885769
TI  - Human trials of HIV-1 vaccines.

PMID- 10885770
TI  - The role of nonhuman primates in the development of an AIDS vaccine.
AB  - Over the past decade, a substantial research investment has generated a vast body
      of knowledge relevant to the development of an effective AIDS vaccine.
      Furthermore, studies in nonhuman primates have demonstrated that a number of
      candidate immunogens can confer a significant degree of protection against a
      potentially pathogenic SIV or SHIV. Currently, there exists a robust program that
      supports discovery of new HIV immunogens and a proven successful program for
      collaborative human trials of promising vaccine candidates. However, we believe
      that there is a gap between discovery and clinical trials. An orderly process for
      screening of candidate immunogens prior to human trials would facilitate the
      vaccine development program. We suggest that nonhuman primates can fill this
      strategic gap and could accelerate vaccine development. Recognizing that there is
      considerable controversy about the potential usefulness of the primate models, we
      have attempted to set forth the relevant practical and biological issues as a
      series of questions for discussion. The most important biological problem is the
      absence of a single immune response correlate that will predict vaccine efficacy.
      Data from primate models indicate that such a single predictive correlate may not
      exist. In turn, this argues for a vaccine screening protocol that includes a
      pathogenic virus challenge, an approach only available in the nonhuman primate
      model. The further assumption is that nonprimate models can be used to predict
      the relative protective efficacy of diverse immunization protocols, a hypothesis
      that can only be tested by comparative studies yet to be conducted. A 'standard'
      set of virus challenges must be selected for comparison of different immunization
      protocols, and this effort has been initiated. At the practical level, it appears
      that the large number of candidate immunogens now being developed requires a
      screening process of the kind proposed, since it would not be practical to test
      all new immunogens and protocols in humans. In conclusion, it appears timely to
      crystallize an orderly process for the discovery, screening, and human testing of
      candidate AIDS vaccines, understanding that a vaccine development program should
      not be conducted at the expense of investigator-initiated research in the diverse
      disciplines that support rational vaccine design and development. The components
      of a rational process of vaccine development are well established and only remain
      to be welded into one coherent program.

PMID- 10885771
TI  - Anti-HIV cellular immunity: recent advances towards vaccine design.

PMID- 10885773
TI  - New insights and approaches regarding B- and T-cell epitopes in HIV vaccine
      design.

PMID- 10885772
TI  - The neutralizing antibody response to HIV-1: viral evasion and escape from
      humoral immunity.

PMID- 10885774
TI  - AIDS 1999. Clinical treatment: overview.

PMID- 10885775
TI  - The year in review: antiretroviral treatment.

PMID- 10885776
TI  - Protease inhibitors: resistance, cross-resistance, fitness and the choice of
      initial and salvage therapies.

PMID- 10885777
TI  - Interruption of materno-fetal transmission.

PMID- 10885778
TI  - Treatment update for AIDS-related Kaposi's sarcoma.

PMID- 10885779
TI  - New approaches to managing opportunistic infections.

PMID- 10885780
TI  - AIDS 1999. Behavioral and social science: overview.

PMID- 10885781
TI  - HIV prevention among vulnerable populations: outreach in the developing world.

PMID- 10885782
TI  - Low fertility in women with HIV and the impact of the epidemic on orphanhood and
      early childhood mortality in sub-Saharan Africa.

PMID- 10885783
TI  - Drug injecting, rapid HIV spread, and the 'risk environment': implications for
      assessment and response.

PMID- 10885784
TI  - Adherence: a necessity for successful HIV combination therapy.
AB  - Patient adherence to combination therapy is a critical component of successful
      treatment outcomes. While combination therapy is known to be effective in slowing
      disease progression, the long-term benefit of these therapies can only be
      sustained if resistant strains of HIV do not emerge. Among factors that can
      result in the emergence of resistance, non-adherence is perhaps the most amenable
      to intervention. To maximize intervention efforts, a program of research on
      adherence is needed. A prerequisite for progress in adherence research is a
      focused effort on developing reliable and valid methods for measuring adherence
      that are feasible for patients living with HIV/AIDS. If new adherence assessment
      procedures cannot be developed, it would be helpful if a consensus on measurement
      approaches could be achieved. This consensus might propose strategies for
      matching measurement approaches with research questions and recommendations for
      the use of multiple measures where appropriate. It is important that research
      continue to identify psychological, physiological, socio-cultural and
      environmental factors that are associated with non-adherence in various
      populations both in the developed and the developing world. Intervention programs
      that address these risk factors and promote adherence need to be developed and
      evaluated in controlled clinical trials. These programs will need to be tailored
      to different populations and cultural groups, and tested in both developed and
      developing countries where HIV therapies are being prescribed. The results of
      this research would significantly contribute to efforts to prevent virus
      breakthrough and, by doing so, assist persons living with HIV/AIDS in achieving
      the health benefits that the combination therapies offer.

PMID- 10885785
TI  - Health, welfare reform, and narratives of uncertainty among Cambodian refugees.
AB  - Massive disruptions to a way of life, such as those brought on by widespread
      violence, terror, and genocide, disorder the body as well as the social order.
      When they flee their homelands, refugees bring their experiences of violence and
      terror with them. Drawing on an ethnographic study of 40 Cambodian refugees
      between the ages of 50 and 79 who suffered from one or more chronic illnesses, we
      explore how refugees who live with chronic illnesses and are dependent on
      government support were affected by the threat of welfare reform. When welfare
      reform threatened to cut Cambodian refugees' income, it posed a new crisis for
      those who were chronically in limbo and placed further constraints on their
      lives. Through their narratives, Cambodian refugees enacted their bodily distress
      and resisted the threat of welfare reform. The story of threatened welfare reform
      in the U.S. and its possible consequences for refugees is a story of quixotic
      U.S. politics, policies and antidotes for refugeeism gone awry.

PMID- 10885787
TI  - Spirit (shen), styles of knowing, and authority in contemporary Chinese medicine.
AB  - Studies on the terminology of expert knowledge tend to neglect the relevance of
      sociological data, in spite of general acceptance that knowledge and social
      practice are interdependent. This paper explores expert knowledge and practice by
      examining 'styles of knowing' and how they differ according to the ways in which
      experts establish their authority. For assessing medical authority in microsocial
      settings, the author takes recourse to Weber's three ideal types. The study shows
      that for a charismatic healer who seeks to reach mutual consensus with his
      clientele vagueness in terminology can be useful. When, however, medical
      authority depends on recognition by superiors and peers in modern bureaucratic
      institutions, vague terms tend to be avoided. So, the same term that a
      charismatic healer may refer to in a vague sense becomes more explicitly defined
      in the bureaucratic setting. Its sense is more clearly delimited and denotational
      qualities are emphasized. In institutions where traditional authority prevails,
      like those of the literate elite in highly stratified traditional societies, the
      technical terminology is not only vague, but notoriously polysemous. The article
      draws on ethnographic data of Chinese medicine and qigong therapy as practised in
      the late eighties in Kunming city, the capital of Yunnan province in the People's
      Republic of China, but it is meant to contribute in a more general way to an
      exploration of the ways in which claims to medical authority interrelate with
      word meaning, language use, and 'styles of knowing'. The term investigated, shen,
      refers to the spiritual, a domain of human experience that is widely acknowledged
      by traditional medical practitioners, but difficult to evaluate by sociological
      analysis.

PMID- 10885786
TI  - Disciplining addictions: the bio-politics of methadone and heroin in the United
      States.
AB  - Biomedical understanding of methadone as a magic-bullet pharmacological block to
      the euphoric effects of heroin is inconsistent with epidemiological and clinical
      data. An ethnographic perspective on the ways street-based heroin addicts
      experience methadone reveals the quagmire of power relations that shape drug
      treatment in the United States. The phenomenon of the methadone clinic is an
      unhappy compromise between competing discourses: A criminalizing morality versus
      a medicalizing model of addiction-as-a-brain-disease. Treatment in this context
      becomes a hostile exercise in disciplining the unruly misuses of pleasure and in
      controlling economically unproductive bodies. Most of the biomedical and
      epidemiological research literature on methadone obscures these power dynamics by
      technocratically debating dosage titrations in a social vacuum. A foucaultian
      critique of the interplay between power and knowledge might dismiss debates over
      the Swiss experiments with heroin prescription as merely one more version of
      biopower disciplining unworthy bodies. Foucault's ill-defined concept of the
      specific intellectual as someone who confronts power relations on a practical
      technical level, however, suggests there can be a role for political as well as
      theoretical engagement with debates in the field of applied substance abuse
      treatment. Meanwhile, too many heroin addicts who are prescribed methadone in the
      United States suffer negative side effects that range from an accentuated craving
      for polydrug abuse to a paralyzing sense of impotence and physical and emotional
      discomfort.

PMID- 10885788
TI  - The framing of teenage health care: organizations, culture, and control.
AB  - Adolescent health is one of the most polemical health issues that has swept the
      United States in recent years. This study is about documenting the process of a
      project on teenage sex, drug, and alcohol abuse in a small rural California town.
      It illustrates a dynamic set of concerns that impinge on health issues:
      development and underdevelopment, experts and lay people, young and old, in a
      context of the transformation of a rural economy to a prison-based industry. It
      is also about covert forms of control, pacification, burnout, and teenagers
      caught in the crossfire between bureaucratic institutions and contradictory
      messages about adolescent health as they correspond to changing conditions
      between institutional power holders.

PMID- 10885789
TI  - Cultural formulation: depression and back pain in a young male Turkish immigrant
      in Basel, Switzerland.

PMID- 10885790
TI  - Biosynthesis of pyridoxine: origin of the nitrogen atom of pyridoxine in
      microorganisms.
AB  - The amide nitrogen atom of glutamine was incorporated into pyridoxine in four
      eukaryotes, Emericella nidulans, Mucor racemosus, Neurospora crassa and
      Saccharomyces cerevisiae, and two prokaryotes, Staphylococcus aureus and Bacillus
      subtilis, but not in the following prokaryotes, Pseudomonas putida, Enterobacter
      aerogenes and Escherichia coli. On the other hand, the nitrogen atom of glutamate
      was incorporated into pyridoxine in P. putida, E. aerogenes and E. coli, but not
      in S. aureus and B. subtilis. These results suggest that there are at least two
      different biosynthetic routes for pyridoxine and the difference does not depend
      on prokaryotes and eukaryotes.

PMID- 10885791
TI  - Cholesterol supplementation attenuates the hypocholesterolemic effect of rice
      bran oil in rats.
AB  - Rice bran oil (RBO), when blended with safflower oil (SFO) at the ratio of 7 to
      3, has been shown to lower serum cholesterol in humans consuming cholesterol. The
      mechanism as to how this oil blend exerts its effect is not yet clear. This study
      examined the effect of cholesterol supplementation on the cholesterol-lowering
      ability of different RBO/SFO blends. Male Sprague Dawley rats (4 wk old) were fed
      purified diets containing 10% fat with or without the addition of 0.5%
      cholesterol for 3 wk. The fat was either SFO or RBO alone, or the mixture of
      these two oils at the ratio of 7: 3 (7S/3R), 5:5 (5S/5R), or 3:7 (3S/7R). Without
      cholesterol supplementation, there were no significant differences in the serum
      and liver total cholesterol levels among different dietary fats. However, the HDL
      cholesterol level of rats fed the RBO-containing diets (especially in rats fed
      the 3S/7R diet) was higher than that of rats fed the diet containing SFO alone.
      This resulted in an increase in the ratio of HDL/total cholesterol-a desirable
      outcome. Supplementation of the diets with 0.5% cholesterol significantly
      increased the cholesterol level in both the serum and the liver. Increasing the
      proportion of RBO in the diet further raised the total cholesterol level in the
      serum whereas it reduced liver cholesterol. Then, the specific effect of the
      3S/7R mixture on the ratio of HDL/total cholesterol disappeared. These findings
      suggest that cholesterol supplemented at the level of 0.5% in this study masked
      the cholesterol-lowering effect of RBO. Smaller percentages of polyunsaturated
      fatty acid (i.e., 18:2n-6) in the RBO-containing diets than in the SFO diet might
      have reduced their ability to dispose the circulating serum cholesterol into the
      liver.

PMID- 10885792
TI  - Cecal environment and TBARS level in mice fed corn oil, beef tallow and menhaden
      fish oil.
AB  - To examine the dietary effects of three lipids from different sources on
      intestinal conditions, diets containing 10% corn oil (CO), 1% corn oil +9% beef
      tallow (BT) or 1% corn oil + 9% menhaden fish oil (MO) were administered to male
      mice for 4 wk. Levels of total cholesterol (TC), non-esterified fatty acids
      (NEFA) and glucose in plasma were lower in mice fed on MO than in mice fed on CO
      or BT. The plasma phospholipid (PL) level was lower for mice fed MO than in mice
      fed BT. Levels of the thiobarbituric acid-reactive substances (TBARS), soluble
      saccharides and soluble proteins in the cecum were significantly higher in mice
      fed on MO than in mice fed on CO or BT. The number of fecal bacteroidaceae was
      lower in mice fed on MO than in mice fed on BT. On the other hand, the number of
      fecal bifidobacteria was greater in mice fed on MO than in mice fed on CO. These
      results suggest the possibility that menhaden oil affects lower intestinal
      microflora through the increase of not only oxide products but also saccharides
      and proteins in the intestine.

PMID- 10885793
TI  - Suppression of glycogen consumption during acute exercise by dietary branched
      chain amino acids in rats.
AB  - The effects of a diet supplemented with branched-chain amino acids (BCAA; 4.8% or
      6.2%) on BCAA catabolism and glycogen metabolism in rats were examined. Rats were
      fed a BCAA diet or control diet for 4 wk and part of the rats were subjected to
      exercise training during the experimental period. Feeding the BCAA diet increased
      serum BCAA concentrations and activity of the hepatic branched-chain alpha-keto
      acid dehydrogenase complex, the rate-limiting enzyme in the catabolism of BCAA,
      suggesting that dietary BCAA promotes BCAA catabolism. Although the serum glucose
      concentration and glycogen contents in the liver and gastrocnemius muscle of
      rested rats were not significantly affected by feeding of the BCAA diet, those in
      rats exhausted by acute exercise were 2-4-fold higher in rats fed the BCAA diet
      than in rats fed the control diet. The activity of pyruvate dehydrogenase complex
      in the liver and gastrocnemius muscle after acute exercise showed reverse trends;
      the complex activities (especially in liver) tended to be less in the BCAA diet
      group than in the control diet group. These results suggest that dietary BCAA
      spares glycogen stores in liver and skeletal muscle during exercise and that the
      decrease in pyruvate dehydrogenase complex activity in these tissues by dietary
      BCAA is involved in the mechanisms.

PMID- 10885794
TI  - Resveratrol attenuates ovariectomy-induced hypertension and bone loss in stroke
      prone spontaneously hypertensive rats.
AB  - We examined the effect of resveratrol (3,4',5-trihydroxy stilbene), a phenolic
      compound found in the skins of most grapes, on blood pressure and bone loss in
      ovariectomized (OVX), stroke-prone spontaneously hypertensive rats (SHRSP).
      Nineteen-week-old female SHRSP were divided into a sham-ovariectomized (sham)
      group fed a control diet and two OVX groups fed either a control diet (OVX-Cont)
      or a diet supplemented with resveratrol (5 mg/kg per d; OVX-Resv). Ovariectomy
      induced significant increases in systolic blood pressure (SBP). Resveratrol
      lowered the SBP by 15%) by the third week of administration, and this effect was
      maintained throughout the study. Resveratrol treatment also significantly
      enhanced endothelium-dependent vascular relaxation in response to acetylcholine
      (ACh) in OVX rats. Finally, femur breaking energies measured for the resveratrol
      treated (OVX-Resv) group were significantly higher than those of the resveratrol
      untreated (OVX-Cont) group. While no significant differences in calcium,
      magnesium and phosphorus content were found between the femurs of OVX-Cont and
      OVX-Resv rats, the femur hydroxyproline content in the OVX-Resv group was
      significantly higher than of the OVX-Cont group. We conclude that, in OVX-SHRSP,
      resveratrol acts by a similar mechanism to mammalian estrogens, lowering blood
      pressure by increasing dilatory responses to ACh. The present study also
      demonstrated that resveratrol was able to prevent ovariectomy-induced decreases
      in femoral bone strength.

PMID- 10885795
TI  - Efficient extraction and some properties of storage proteins (prolamin and
      glutelin) in ancient rice cultivars.
AB  - Two typical storage proteins (prolamin and glutelin) in a total of 14 samples of
      ancient rice cultivars were examined for their accumulation in the endosperms
      during days after flowering (DAF), extraction efficiency with various solvents,
      and variations in polypeptide components or amino acid compositions. There was
      little difference in accumulation profiles between this and previous
      observations, in which glutelin appeared on 5-7 DAF and prolamin on 7-9 DAF. As
      for the extraction of prolamin and glutelin, it was most effectively attained by
      sequential usage of 55% propanol and 21% SDS. As a result of SDS-PAGE, prolamin
      and glutelin proved to be composed mainly of a single polypeptide with a
      molecular weight (MW) of 15 kDa and two subunits with MWs of 21 kDa (alpha) and
      32 kDa (beta), respectively. A comparison between the ancient and modern rice
      cultivars revealed the same physicochemical properties in either case of prolamin
      or glutelin. Additionally, a good relationship was observed on the total protein
      and glutelin (but not prolamin) contents in the ancient rice cultivar.

PMID- 10885796
TI  - Antitumorigenic effects of several food proteins in a rat model with colon cancer
      and their reverse correlation with plasma bile acid concentration.
AB  - In order to obtain information on the preventive effects of various food proteins
      against colonic cancer, six groups of azoxymethane-initiated mature Fischer rats
      (n = 10) were fed respective diets different in protein sources such as bovine
      milk casein (casein), high-molecular-weight fraction from protolytic digest of
      soy protein isolate (soybean HMF), hen's yolk defatted protein (yolk protein),
      wheat gluten and codfish meat, which had been supplemented with sodium
      deoxycholate (hereinafter, DCA) as a cancer promoter except for an additional DCA
      unfed casein group. All of the living rats at checkpoints during the feeding
      period were examined by the use of a bronchus fiberscope for colonic tumor
      incidence at 6 wk intervals between the 10th and 34th wk, from which both blood
      and feces samples were taken at times of endoscopy. Tumorigenesis in the colon
      was perceived by endoscopy at wk 22 in the group fed DCA casein only and at wk 28
      in the other groups except the DCA-unfed casein group. At wk 34, both soybean HMF
      and yolk protein groups ranked inferior to the DCA-unfed group in tumor
      incidence. When plasma steroid or lipid concentration was plotted against tumor
      incidence at wk 28 or 34, positive correlations were found between plasma bile
      acid concentration and tumor incidence at both weeks. With the exception of the
      DCA-unfed casein group, plasma bile acid concentration was reversely correlated
      to fecal bile acid excretion. Taken altogether, these results suggest that bile
      acids at higher concentrations in the plasma may serve as risk factors of colon
      tumor incidence.

PMID- 10885797
TI  - Forms of vitamin B12 compounds containing sulfitoB12 in corbiculas.
AB  - Forms of vitamin B12 (B12) compounds in young and aged corbiculas were examined
      by bioautography using B12-requiring microorganisms combined with cellulose
      acetate membrane electrophoresis or high-performane liquid chromatography (HPLC).
      Both corbiculas (per 100 g) contained ca. 30 microg of cobalamin, a complete type
      of B12. Five known B12 compounds, adenosylB12 (AdoB12), methylB12, hydroxoB12,
      sulfitoB12 and cyanoB12, were identified by bioautography. Young corbicula
      contained more B12 compounds, assumed as methylB12, AdoB12 and sulfitoB12, as
      compared to aged corbicula. All of the B12 compounds detected around the location
      corresponding to those of methylB12, AdoB12 and sulfitoB12 in the bioautography
      were converted into compounds that behaved like hydroxoB12 after photolysis.
      Young corbicula was found to contain an unidentified B12 compound using
      bioautography combined with HPLC. A large portion of the B12 compound that moved
      like hydroxoB12 during cellulose acetate membrane electrophoresis using 0.5 N
      acetic acid might be identical with the unidentified B12 compound detected in the
      HPLC-bioautography.

PMID- 10885798
TI  - HPLC analysis and optimization of enzymatic synthesis of 4'-O-(beta-D
      glucopyranosyl)-D-pantothenic acid.
AB  - We analyzed beta-glucosidase-catalyzed transglucosylation to D-pantothenic acid
      using a reversed-phase HPLC system in order to obtain 4'-O-(beta-D
      glucopyranosyl)-D-pantothenic acid (PaG) at a higher yield. The HPLC system was
      simpler and more straight-forward for the PaG analysis than the previously
      employed bioassay method and could also be adopted for efficient isolation of
      PaG. Penicillium decumbens naringinase showed the highest glucosyl transfer
      activity to D-pantothenic acid, and the reaction using smaller amounts of
      naringinase for prolonged periods of reaction time (70 h<) was important to
      attain higher yields of glucosyl transfer. Maximum overall yields of PaG of 10
      and 4% (mol/mol, based on D-pantothenic acid) were obtained using beta, beta'
      trehalose and cellobiose, respectively, as glucosyl donors. The value was 3.6-
      and 1.4-times higher, respectively, than that obtained by previous synthesis and
      isolation procedures.

PMID- 10885799
TI  - Effect of soy milk and bifidobacterium-fermented soy milk on plasma and liver
      lipids in ovariectomized Syrian hamsters.
AB  - The effects of soy milk and fermented soy milk on lipid metabolism were studied
      in ovariectomized Syrian hamsters. Five mo-old Syrian hamsters were randomly
      assigned to four treatment groups: ovariectomized (OVX)+control diet (OVX-C);
      OVX+soy milk diet (OVX-SM); OVX+fermented soy milk diet (OVX-FSM); and sham
      operated+control diet (Sham-C). The hamsters were fed on these diets for 4 wk.
      The atherogenic index value of the OVX-FSM group was lower than that of the OVX-C
      group. The plasma triglyceride level of the OVX-FSM group was significantly lower
      than that of the OVX-C group. The liver total cholesterol contents in the OVX-SM
      and OVX-FSM groups were significantly lower than that in the OVX-C group. Thus,
      these results demonstrate that bifidobacterium-fermented soy milk had a
      hypolipidemic effect in ovariectomized hamsters.

PMID- 10885800
TI  - Structural and immunochemical homologies between foxtail millet glutelin 60 kDa
      and starch granule-bound starch synthase proteins from rice, barley, corn and
      wheat grains.
AB  - Foxtail millet glutelin 60 kDa (MG60) was purified by preparative SDS-PAGE, and
      the N-terminal amino acid sequence was determined within 20 residues. The result
      demonstrated that the primary structure at N-terminal of MG60 was almost
      identical to those of the granule-bound starch synthase (GBSS) proteins from
      rice, barley, corn, wheat and potato. The existence of common epitopes among MG60
      and GBSS proteins from these starch-storing cereals were corroborated by
      immunoblot analysis using antisera raised against MG60. These facts strongly
      suggest a close relationship between MG60-like glutelins and GBSS proteins.

PMID- 10885801
TI  - Nutritional modulation of aging in nonhuman primates.
AB  - Caloric restriction (CR), undernutrition without malnutrition, remains the only
      experimental paradigm that has been shown consistently to extend lifespan and
      slow aging in short-lived species. Decades of research, mostly in laboratory
      rodents, have shown that CR consistently extends lifespan, reduces or delays the
      onset of many age-related diseases and slows aging in many physiological systems.
      In recent years gerontologists interested in CR have focused on two unanswered
      questions. 1) What is the relevance of this nutritional paradigm to human aging?
      and 2) What biological mechanism(s) underlie the diverse effects of CR leading to
      a retardation of aging and disease?. To address the question of human relevance,
      researchers in the Intramural Research Program of the National Institute on Aging
      began a study of CR in nonhuman primates in the late 1980s. In addition to
      assessing the effects of CR on aging in primates, a major focus of this work
      relates to possible metabolic mechanisms of CR. A subsequent study at the
      University of Wisconsin Madison was initiated in the early 1990s. Certain aspects
      of experimental design differ between these two important ongoing investigations,
      but generally these studies compliment each other in many ways and have begun to
      provide much important data regarding the effects of CR in primates. Emerging
      data from these studies strongly support that physiological responses to CR in
      monkeys parallel the extensive findings reported in rodents. Lifespan data will
      not be available for several years, however, the remarkable consistency with
      rodent studies, in which lifespan extension is documented extensively,
      strengthens the possibility that CR will also extend lifespan in primates,
      perhaps including humans. This review summarizes the major findings from the
      primate CR studies after over a decade of research in this model.

PMID- 10885802
TI  - Caloric restriction and aging.
AB  - Caloric restriction in species with a short life span has shown it can increase
      median and maximum life expectancy and reduce or delay the onset of most age
      related diseases. The remarkable reproducibility of the phenomenon irrefutably
      proves its validity and makes caloric restriction one of the most frequently
      studied paradigms in experimental research on aging.

PMID- 10885803
TI  - Diet and ageing: the possible relation to reactive oxygen species.
AB  - The hypothesis that the generation of reactive oxygen species (ROS) is the
      principal mechanism responsible for ageing, is reviewed in relation to the
      influence of diet and dietary factors on the generation of ROS and the effects on
      life span. Particular focus has been placed on the generation of ROS in the
      mitochondria, the effects this has on oxidative damage to cellular
      macromolecules, and the evidence that dietary factors can reduce this damage.
      Support for the hypothesis that the generation of ROS is a major causative factor
      in ageing depends on the demonstration that dietary factors, which are
      antioxidants, or which will reduce the rate of generation of ROS, will increase
      life span. The experimental evidence so far is not strong, apart from the
      consistent observation, across many species, that caloric restriction increases
      longevity. Proof that antioxidants are beneficial is mainly limited to the
      demonstration that they do increase average life span, principally through a
      reduction in the incidence of life-threatening diseases in animals, but there is
      little current evidence to support an increase in maximum life span. Since the
      experimental approach to date has been phenomenological, rather than
      mechanistically based, there is a need for further studies to be undertaken
      looking at specific mechanisms which are known to be influenced by antioxidants.

PMID- 10885804
TI  - Roles for insulin-like growth factor-1 in mediating the anti-carcinogenic effects
      of caloric restriction.
AB  - This paper focuses on the role of insulin-like growth factor-1 (IGF-1) and its
      associated regulatory apparatus as a key endocrine, autocrine, and paracrine
      signalling system involved in mediating the anti-carcinogenic activity of dietary
      restriction. Literature is reviewed showing that the inhibitory action of dietary
      restriction on carcinogenesis is global and pervasive--it is effective in several
      laboratory species, for a variety of tumor types, and for both spontaneous tumors
      and tumors caused by different types of tumor-inducing agents. Evidence is
      presented showing the IGF-1 pathway responds appropriately to nutritional
      interventions including diet restriction. Recent evidence points to an obligatory
      role for the IGF-1 receptor in the establishment and maintenance of the
      transformed phenotype and reveals that IGF-1 in concert with insulin-like binding
      protein 3 and p53 is involved in autocrine/paracrine growth signaling pathways as
      adaptive responses to environmental stimuli. Considered together these works show
      that the IGF-1 pathway is uniquely poised to influence cellular transformation
      leading to the malignant phenotype by modulating the balance of cellular
      proliferation and cell death (apoptosis) in precancerous and cancerous cells and
      by influencing metastasis of nascent tumors. We evaluated these hypotheses
      directly using animal models of mononuclear cell leukemia, bladder transitional
      cell carcinogenesis, and breast cancer. Our studies demonstrate that manipulation
      of IGF-1 level through dietary intervention influences tumor growth and
      metastasis. Upregulation of this pathway demonstrated that increased IGF-1
      stimulates tumor proliferation, progression and metastasis. Conversely,
      downregulation of this pathway in vivo as a consequence of dietary restriction
      results in antitumorigenic activity. We found that the functional disruption of
      IGF-1R markedly influences breast cancer metastasis in nude mice by suppressing
      cellular adhesion, invasion, and metastasis of breast cancer cells to the lung,
      lymph nodes, and lymph vessels. Epidemiological observations and clinical
      oncology results support the involvement of IGF-1 in carcinogenesis and
      anticarcinogenesis. This leads to the hypothesis that factors such as IGF-1 which
      regulate body size and composition may be related to human cancer incidence or
      prognosis. Additional understanding of this pathway and its interactions with
      other signaling pathways will advance our ability to develop new interventions
      towards decreased cancer risk in humans.

PMID- 10885805
TI  - Caloric restriction and genomic stability.
AB  - Caloric restriction (CR) without malnutrition is the only experimental
      manipulation that has consistently been shown to increase the mean and maximum
      lifespan of laboratory rodents. It has been suggested that CR extends the
      longevity of rodents and reduces the incidence of age-related pathological
      lesions by reducing the levels of DNA damage and mutations that accumulate with
      age within a cells genome. This hypothesis is attractive because the integrity of
      the genome is essential to a cell/organism and because it is supported by the
      observations that both cancer and immunological defects, which increase
      significantly with age and are delayed by CR, are associated with changes in DNA
      damage. However, all the evidence supporting the premise that the accumulation of
      DNA damage/mutations plays a role in aging and CR is correlative, i.e., the anti
      aging action of CR-fed rodents is correlated with decreased DNA damage and
      mutation and increased DNA repair capacity. Therefore, additional experiments are
      required which employ more accurate assays of the DNA repair pathways as well as
      genetically engineered animal models to establish the role of specific DNA repair
      pathways and/or enzymes in the anti-aging action of CR. In this paper, we review
      the proposed mechanisms of DNA damage/repair while providing insight into current
      research that may assist in "unlocking" the mechanisms behind the life-prolonging
      effect of CR.

PMID- 10885806
TI  - Aging and DNA polymerase alpha: modulation by dietary restriction.
AB  - Aging is an inevitable characteristic of biological processes in living
      organisms. For the last several years, investigators have proposed numerous
      mechanisms to explain the basic understanding of aging and its intervention and
      have provided many insights into the molecular bases and the biological events
      that contribute to the progressive decline in function observed during cellular
      aging. It is probable that a number of interacting factors, such as increased
      somatic mutations, changes in genetic expression, and decreased efficiency of
      protein synthesis, may contribute to the age-dependent deterioration of
      physiological processes. One cellular function involved in all of the above
      factors is that of normal DNA synthesis required for maintaining genomic
      integrity. This suggests that changes in function of DNA replicative enzymes are
      almost certain to be a factor in one or more of the negative cellular phenomena
      associated with aging. This is a particularly attractive hypothesis, since the
      accumulation of inactive or error-prone DNA polymerases during aging would be
      expected to initiate a sequence of events leading to synthesis of altered
      proteins and the general dysfunction of a wide range of cellular processes.
      Dietary restriction is the only anti-aging regimen uniquely suited to identifying
      these cellular processes and could play a significant role in maintaining
      cellular mechanisms necessary to reduce the rate at which mutations accumulate
      during aging. The observation that dietary restriction may impede the age-related
      decline in the activity and fidelity of DNA polymerases and in the decline of
      repair DNA synthesis, suggests potential mechanisms by which dietary restriction
      could extend the lifespan of animals, including humans.

PMID- 10885807
TI  - Calorie restriction and spontaneous hepatic tumors in C3H/He mice.
AB  - Caloric restriction started at the young adult (YA) stage and the full adult (FA)
      stage in mice was compared, specifically focussing on whether there would be a
      delay in the onset time of spontaneous hepatoma or a reduction in its frequency.
      Caloric restriction lengthened the life spans of both groups, the YA, and FA.
      Both groups showed striking reductions of spontaneous hepatomas, from 70.9 +/-
      3.5% for non-restricted controls down to 35.7 +/- 5.7 and 30.4 +/- 4.0%, for mice
      restricted from young adult, and from full adult stages, respectively; further,
      the numbers of tumor-free mice in the restricted groups increased by 45.7% and
      38.5%, respectively, from 11.5%, in the non-restricted control. The cumulative
      incidences of hepatoma in the caloric restricted groups showed a delayed and
      lower incidence compared with those of the non-restricted group; a parallel delay
      might result from a weakened activity in tumor-promotion, whereas a lower
      frequency, might reflect a possible reduction of target cells for hepatomata
      development. Both effects can be assumed to have resulted from caloric
      restriction. When cumulative incidences of small hepatomas were compared between
      the two restricted groups, restriction started at the young adult stage is
      assumed to have caused fewer initiation stresses, as well as to have delayed
      promotion, as clearly evidenced by a flatter curve of incidence with a lower
      total incidence. Thus, the time at which caloric restriction is started plays a
      critical role in its subsequent effects.

PMID- 10885808
TI  - Hormonal induced lactation in transgenic goats.
AB  - The aim of this study was to hormonally induce lactation in prepubertal,
      nulliparous, and male goats both transgenic and non-transgenic. Analysis of milk
      quality, recombinant protein expression levels, total amount of recombinant
      protein produced, and the affect on long-term reproductive capability was
      assessed. Fifty-one goats (Saanen, Alpine, and Toggenburg), male and non-pregnant
      females, 2-31 months of age, either non-transgenic or transgenic were evaluated
      with a total of 10 transgenes (constructs) represented. Animals were given
      estradiol (0.25 mg/kg, i.m.) and progesterone (0.75 mg/kg, i.m.) on days 1, 3, 5,
      7, 9, 11 and 13, while prednisilone (0.4 mg/kg, i.m.) was administered on days 14
      16 with mammary massage occurring daily from day 5 onward. Forty of 51 animals,
      (36 of 38 females and 4 of 13 males) produced milk with total volumes in the 30
      day experiment, ranging from 20 microl to 530 mls per day, or approximately 500
      microl to 6.8 liters total. Milk composition was analyzed for various parameters
      (total protein, fat content, total solids and somatic cell count) with no
      significant differences found between induced and natural milk. Expression levels
      of recombinant proteins from transgenic animals that were analyzed during the
      induced lactation, and subsequently during normal lactations, were found to have
      no significant differences. Total amount of recombinant protein produced was
      evaluated at different expression levels with no statistical significance seen.
      While over 90% of the females placed in the regimen became pregnant, there was a
      correlation between increased age at time of induction and an increase in number
      of breedings, or reproductive cycles needed to establish a pregnancy after
      induction. For males, 100% placed in the regimen settled females after hormonal
      induction of lactation. Semen quality was evaluated prior to, during, and after
      hormonal treatments. Semen volume and sperm number did not differ; however, for a
      small percentage of males, there was a decrease in sperm and post thaw motility
      after hormonal treatments. These levels returned to normal within 4-5 weeks.
      Subsequent natural lactations showed total milk volumes within breed standards.
      These findings indicate that hormonal induction of lactation in the caprine
      species is a viable alternative to pregnancy for initiating lactation and milk
      production, does not adversely impact reproductive performance long-term, and can
      benefit the early assessment of recombinant proteins produced in a transgenic
      founder program.

PMID- 10885809
TI  - DNA preparation method can influence outcome of transgenic animal experiments.
AB  - In our continuing quest to improve the efficiency of producing transgenic
      animals, we have compared the influence of two transgene purification techniques
      on the efficiency of creating transgenic sheep and mice. Three hundred eighty
      seven sheep zygotes and 2,737 mouse zygotes were microinjected with one of four
      transgenes. Transgenes were isolated from plasmid sequences either by agarose gel
      electrophoresis followed by gel extraction or by a single step sodium chloride
      gradient fractionation technique. Four transgenic sheep and 61 transgenic mice
      were produced. Both sheep and mice embryos responded similarly to transgene
      preparation methods. Overall, pregnancy rate was higher for recipients that
      received embryos injected with NaCl purified DNA (mean +/- SEM: 64 +/- 7% vs. 38
      +/- 7%). Furthermore, offspring per zygote transferred (NaCl, 22 +/- 3% vs. Gel,
      12 +/- 3%) and transgenics born per zygote transferred (NaCl, 3.9 +/- 0.6% vs.
      Gel, 1.5 +/- 0.6%) were higher when the NaCl purified DNA was used. However, the
      proportion of offspring born that were identified as transgenic did not differ
      between transgene purification methods. Transgenes responded differently to
      methods of preparation. One of the four genes yielded a significantly higher
      proportion of transgenics when the transgene was prepared by NaCl purification.
      These data suggest that on average the NaCl gradient purification technique
      results in a higher embryo survival rate to term for both sheep and mice, but the
      technique has no influence on rate of transgene integration.

PMID- 10885810
TI  - Isolation of thirty-one new porcine microsatellites from a microsatellite
      enriched microdissected chromosome 8 library.
AB  - Chromosome 8 (SSC8) is an important one in the swine genome because it has been
      shown to harbor several economically important quantitative trait loci (QTL). The
      entire porcine chromosome 8 was microdissected and amplified by degenerate
      oligonucleotide primer (DOP) PCR. The PCR product was then enriched for (CA)n
      microsatellites by hybridization to a biotinylated CA repeat oligonucleotide and
      captured by streptavidin-coated magnetic beads. The captured DNA was cloned into
      a TA cloning vector. Screening with an isotopically labeled CA oligonucleotide
      probe resulted in the isolation of 31 informative and polymorphic microsatellite
      clones. Seventeen of those were mapped to chromosome 8, 12 to chromosome 15, 1 to
      chromosome 10 and 1 to chromosome X. The markers were all placed on the USDA-MARC
      porcine genetic linkage map.

PMID- 10885811
TI  - Ordering three microsatellites on porcine chromosome 12 by single sperm typing.
AB  - Three microsatellite loci on porcine chromosome 12 were ordered by single sperm
      typing to expand the limited genetic map of this region. Individual sperm cells
      from a Chinese indigenous Qingping boar triply heterozygous at SW874, SW1350 and
      SW1553 were amplified using PEP and heminesting primer design at each locus.
      Analysis of the sperm typing data by the SPERM.FOR program showed that the most
      likely order was SW1553-SW1350-SW874.

PMID- 10885812
TI  - Expression of X inactive specific transcript (Xist) and testicular morphogenesis
      in bovine fetuses.
AB  - Inactivation of one of the 2 X chromosomes in the somatic cells of female mammals
      is the process by which their X-linked gene products are equalized to those of
      their male counterparts. In male mammals, however, a sex vesicle representing the
      condensed and transcriptionally silenced sex chromosomes is detected during early
      meiotic prophase. Since the exact stage of development at which X inactivation is
      initiated in the bovine testis is not established as yet, we undertook to study
      fetuses ranging in age from 30 to 180 days of gestation, to determine the
      transcriptional status of the Xist gene currently thought to be the prerequisite
      component of X inactivation. Our studies using reverse transcription polymerase
      chain reaction (RT-PCR) approach with primers designed to amplify a 463 bp
      product from a conserved region of the first exon of bovine Xist gene, proved
      that Xist expression is evident in bovine fetal testes as early as 50 days of
      gestation and that it continues at least to the end of the second trimester (180
      days) of gestation. Morphological studies on fetal testes during gestational
      stage spanning the period of Xist expression revealed the presence of large intra
      tubular cells overtly resembling the prespermatogonia of postnatal bovine testes,
      at 50 days and preleptotene like cells as early as 90 days of gestation. We
      hypothesize that the expression of the Xist gene, or the recently discovered Tsix
      gene antisense to Xist in orientation, may be related to the presence of these
      cells which participate in the morphogenesis of the fetal bovine testis.

PMID- 10885813
TI  - Single nucleotide polymorphisms in an intron of the ovine calpastatin gene.
AB  - Calpastatin is the specific inhibitor of the ubiquitous calcium-dependent
      proteases mu-calpain and m-calpain. Enzyme assay data from sheep and cattle
      inversely correlates post-mortem muscle calpastatin levels with ultimate meat
      tenderness. Genetic markers of meat quality may therefore be found linked to the
      calpastatin gene (CAST). A three-allele system detected by polymerase chain
      reaction-single strand conformational polymorphism (PCR-SSCP) has been observed
      in the ovine CAST. The three allele amplimers have been fully nucleotide
      sequenced and their differences in terms of single nucleotide polymorphism (SNPs)
      in the intron region of the amplimer are reported and compared to a consensus
      sequence of the orthologous region of the cattle CAST. A PCR-RFLP for more rapid
      CAST genotyping of all three ovine alleles was also developed.

PMID- 10885814
TI  - PCR-based detection of the polymorphism at codon 136 in the ovine prion protein
      gene.
AB  - In many breeds of sheep, a polymorphism at codon 136 of the prion protein gene
      has been shown to be strongly associated with the risk of developing scrapie. A
      single-step procedure for detecting this allelic variation is described here.
      When performed on a series of animals, the test was in complete agreement with
      their genotypes as had been previously determined by sequencing. The test is
      potentially easier and quicker to perform than any of the variety of methods that
      are currently used for this purpose.

PMID- 10885815
TI  - Traumatic medial malleolar fracture of a fibula flap donor leg.
AB  - A 50-year-old male presented with a T4 N0 squamous cell carcinoma of the floor of
      the mouth and alveolus. Treatment included a partial mandibulectomy with a free
      osteocutaneous fibula flap reconstruction. He made a good postoperative recovery
      and was given adjuvant radiotherapy. No problems were reported with the donor
      site or ankle. Five months after harvesting the flap the patient sustained a
      fracture of the medial malleolus having jumped over a ditch playing golf. This
      was treated successfully with a below knee plaster of Paris cast. The
      interosseous membrane was not ruptured in the accident indicating that the distal
      fibula left in situ was adequate to maintain the integrity of the mortice. A
      degree of ankle instability may be present after fibula flap harvest which is
      only revealed by athletic activity.

PMID- 10885816
TI  - Simultaneous avulsion fracture of the insertion of the ulnar and radial
      collateral ligaments of the metacarpophalangeal joint of the thumb.
AB  - We present a case of simultaneous avulsion fracture of the insertion on the volar
      base of the proximal phalanx of the ulnar and radial collateral ligaments of the
      metacarpophalangeal joint of the thumb. To our knowledge this combination has
      never been published before. The mechanism of this injury is not clearly
      understood.

PMID- 10885817
TI  - Development of microbial resistance: a global problem. Proceedings of an
      international satellite symposium to the 9th European Congress of Clinical
      Microbiology and Infectious Diseases. Munich, 19-20 March 1999.

PMID- 10885818
TI  - Drug resistance among clinical isolates of frequently encountered bacterial
      species in central Europe during 1975-1995. Study Group Bacterial Resistance of
      the Paul-Ehrlich-Society for Chemotherapy.
AB  - A multicenter study for monitoring antimicrobial drug resistance in clinical
      isolates of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus
      and Enterococcus species in central Europa conducted by the Study Group Bacterial
      Resistance of the Paul-Ehrlich-Society for Chemotherapy has been ongoing since
      1975. Between 1975 and 1995 susceptibility data on almost 60,000 bacteria, which
      were isolated and sampled under a common protocol by laboratories from Austria,
      Germany and Switzerland, were collected. These bacterial isolates were known by
      the respective investigators to have caused infections. From 1975 to the mid-80s
      none of the bacterial species examined showed an increase in resistance. The
      frequency of resistance in klebsiellae and Staphylococcus aureus to some
      antibiotics even declined. In 1990 and particularly in 1995, a clear increase in
      resistance for a number of antibiotic-organism pairs was observed. Resistance
      rates to fluoroquinolones increased in all species under investigation. In
      Escherichia coli the increase of resistance to ampicillin, co-trimoxazole and
      gentamicin was remarkable. Resistance to imipenem increased in P. aeruginosa.
      Resistance to cephalosporins, on the other hand, remained largely unchanged in
      gram-negative bacilli. Between 1990 and 1995, the prevalence of oxacillin
      resistance increased from 1.7 to 12.9% in S. aureus and from 15.8 to 55.8% in
      coagulase-negative staphylococci, whereas staphylococcal and enterococcal
      resistance to glycopeptides was still rare.

PMID- 10885819
TI  - Epidemiology of resistance to antimicrobial drugs in the major respiratory
      pathogens circulating in Europe.
AB  - There is an overwhelming consensus on the fact that Streptococcus pneumoniae,
      Haemophilus influenzae and Moraxella catarrhalis represent the prevailing
      bacterial pathogens of community-acquired lower respiratory tract infections.
      Their specific incidence as causative agents of the more common syndromes is
      known to vary even profoundly depending on geographic location, and the same
      holds true for the rates of resistance to antimicrobial drugs. Europe does not
      escape the threat posed by the present pandemic spread of penicillin resistance
      in S. pneumoniae although, as expected, countries like Spain and France are
      greatly affected, while others including Germany, Italy, The Netherlands and the
      Scandinavian region are comparatively spared. In several sites multiple
      resistance has been described in S. pneumoniae and the most affected drugs
      include penicillin, the macrolides, co-trimoxazole and tetracycline. In H.
      influenzae synthesis of beta-lactamases the main trait of resistance is
      expressed. Lack of susceptibility to beta-lactams dictated by a different
      mechanism remains extremely rare. Considerable variations in the incidence of
      this characteristic are apparent when European countries are considered. France
      and Spain are again widely affected, while Germany, The Netherlands and Italy
      display rates of beta-lactamase-positive H. influenzae of about 10%. M.
      catarrhalis must be considered generally resistant to non-protected
      aminopenicillins since over 90% of these organisms produce beta-lactamases.

PMID- 10885820
TI  - Epidemiology of MRSA.
AB  - Staphylococcus aureus is recognized as one of the major causes of infections in
      humans occurring in both the community and the hospital. Up to now one of the
      most serious aspects as far as treatment of S. aureus infections is concerned is
      resistance to methicillin, which in clinical terms indicates resistance to all
      beta-lactam antibiotics. The growing incidence of methicillin-resistant S. aureus
      (MRSA) infections worldwide, their multidrug resistance, several reservoirs of
      resistant strains, the facility to spread also outside hospitals and to cause
      outbreaks requires efficacious infection control measures. For this reason
      microbiological and epidemiological studies are of crucial importance.

PMID- 10885821
TI  - Epidemiology of resistant tuberculosis in Europe.
AB  - About one-third of the world's population has been infected with Mycobacterium
      tuberculosis (MTB). Active disease develops in eight to ten million people per
      year, and tuberculosis is responsible for three million deaths every year. This
      makes it the leading cause of death due to infections in the world. In 1996,
      315,892 cases of tuberculosis were reported in 50 countries of the WHO European
      region. The notification rate was less than 20 per 100,000 in 21 countries, all
      of which are situated in the western part of Europe except the Czech Republic and
      Israel. The rate was 20 cases per 100,000 or more in 29 countries located in the
      eastern part of Europe except for Portugal and Spain. In addition to the rise of
      tuberculosis observed worldwide, the emergence of drug-resistant tuberculosis
      (TB) poses a major threat to TB control efforts. The prevalence of resistance is
      increasing dramatically, predominantly in eastern Europe. The aim of this article
      is to describe the situation of resistant TB in Europe, and to point out reasons
      for the increase of drug-resistant MTB strains.

PMID- 10885822
TI  - Drug resistance in intensive care units.
AB  - Intensive care units (ICUs) are generally considered epicenters of antibiotic
      resistance and the principal sources of outbreaks of multi-resistant bacteria.
      The most important risk factors are obvious, such as excessive consumption of
      antibiotics exerting selective pressure on bacteria, the frequent use of invasive
      devices and relative density of a susceptible patient population with severe
      underlying diseases. Infections due to antibiotic-resistant bacteria have a major
      impact on morbidity and health-care costs. Increased mortality is not uniformly
      shown for all of these organisms: Methicillin-resistant Staphylococcus aureus
      (MRSA) seems to cause significantly higher mortality, in contrast to vancomycin
      resistant enterococci (VRE). Therefore it is essential to diminish these
      potential risk factors, especially by providing locally adapted guidelines for
      the prudent use of antibiotic therapy. A quality control of antimicrobial therapy
      within a hospital, and especially within the ICU, might help to minimize the
      selection of multidrug-resistant bacteria. The restricted use of antimicrobial
      agents in prophylaxis and therapy has also been shown to have at least temporal
      effects on local resistance patterns. New approaches to the problem of drug
      resistance in ICUs are badly needed.

PMID- 10885823
TI  - Combination therapy as a tool to prevent emergence of bacterial resistance.
AB  - Emergence of resistance is an ever increasing problem. One of the methods by
      which emergence of resistance may possibly be prevented, or at least delayed, is
      the use of combination therapy. Since the emergence of resistant mutants is a
      direct result of selective pressure by antimicrobial therapy, the chance of
      mutants resistant to two antimicrobials in the parent population being present is
      a product of mutation frequencies, provided that resistance mechanisms are
      independent. Comparative studies in in vitro pharmacokinetic models and in vivo
      indicate that emergence of resistance is less common when combination therapy is
      used. This is particularly true for microorganisms known to develop resistance
      relatively quickly, such as Pseudomonas aeruginosa, and resistance mechanisms
      which occur at a relatively high frequency.

PMID- 10885824
TI  - The prevention of antibiotic resistance during treatment.
AB  - Prevention of emergence of antibiotic resistance during treatment is an important
      goal when prescribing antimicrobials. Antibiotic resistant bacteria can emerge in
      three main ways--by acquisition of new genes via transposons or horizontal gene
      transfer, by selection of resistant variants and by selection of naturally
      resistant strains. In order to minimize emergence of antibiotic resistance during
      therapy it is important to try and avoid antibiotics which encourage the transfer
      of resistance genes, to avoid selection of resistant variants from susceptible
      pathogens and to avoid ablation of antibiotic susceptible normal flora. However,
      implementing these objectives is not always easy. This paper discusses possible
      ways of limiting the emergence of resistant bacteria during treatment. It does
      not consider how to prevent the spread of these strains from person to person.
      The prevalence of antibiotic-resistant bacteria depends upon the selection of
      antibiotic-resistant strains and spread of these strains from person to person.
      Prevention therefore consists of two parts--the prevention of acquisition of
      resistance/selection of antibiotic-resistant variants and interrupting the
      mechanisms by which person-to-person spread can occur. This paper considers only
      the first of these two influences on prevalence of resistance.

PMID- 10885825
TI  - Antimicrobial resistance--pharmacological solutions.
AB  - The interaction between microbial resistance and antibacterial agents occurs in a
      direct and an indirect fashion. Directly--through the development of resistance
      to the agent used, or to agents of the same class--as exemplified by the
      induction of beta-lactamase by both gram-positive and gram-negative bacteria. It
      also takes place through the development of resistance to compounds of different
      classes to the compound used, as exemplified by the loss of Streptococcus
      pneumoniae susceptibility to penicillin that is accompanied by a parallel loss of
      sensitivity to erythromycin and to tetracycline. As for the indirect way-
      microbial resistance may develop through selection of resistant organisms when
      the patient is treated with antibiotics, when the environment is contaminated
      with antibiotics (hospital) or when antibacterial agents are used in agriculture
      and animal husbandry.

PMID- 10885827
TI  - Recent developments in the epidemiology of virus diseases and BSE.
AB  - There is a continuous change in viral epidemics with respect to clinical
      symptoms, their duration or disappearance and the emergence of new diseases. This
      can be observed both in human and animal diseases. This evolution of virus
      diseases is mainly related to three factors: etiological agent, host and
      environment. As far as genetic alterations of the virus are concerned, two major
      mechanisms are involved: 1) mutations such as recombination and reassortment; 2)
      selection for resistance or susceptibility. The epidemiology of newly emerged
      virus diseases in man and animals, such as AIDS and hemorrhagic fevers, and
      bovine spongiform encephalopathy (BSE), canine hemorrhagic gastroenteritis or
      respiratory syndrome in horses will be discussed.

PMID- 10885826
TI  - Selective pressure by antibiotics as feed additives.
AB  - Antibacterial substances are used in considerable amounts as growth promoters in
      animal husbandry. There are, however, incalculable risks for human health
      resulting from the use of particular feed additives. Even 30 years ago the
      detection of transferable antibiotic resistance in Enterobacteriaceae led to the
      demand that antibiotics used in human chemotherapy, or for which cross-resistance
      against human therapeutics has been demonstrated, should be prohibited as growth
      promoters. The application of molecular methods to typing and characterization of
      bacteria and their resistance genes has provided more concise evidence for the
      transfer of antibiotic resistance among animal husbandry and humans as to
      resistance to glycopeptides (vanA gene cluster) and to streptogramins (satA).

PMID- 10885828
TI  - Pharmacological issues relating to viral resistance.
AB  - Anti-HIV drug regimens can fail for a number of reasons including virological
      resistance, difficulties of adherence and poor tolerability. However, this brief
      review focuses on the development of "pharmacological" resistance as an area of
      great importance in drug failure. For nucleoside reverse transcriptase inhibitors
      (NRTIs) this is related to the possible down-regulation of the intracellular
      phosphorylation of an NRTI with time. For protease inhibitors the concern is
      cells expressing transmembrane energy-dependent transporters (such as p
      glycoprotein, p-gp; or multi-drug resistance protein, MRP) which efflux drug
      (particularly protease inhibitors) out of the cell so that intracellular
      concentrations of drug are insufficient for antiviral effect.

PMID- 10885829
TI  - Development of resistance and perspectives for future therapies against hepatitis
      B infections: lessons to be learned from HIV.
AB  - Several first-generation nucleoside analogues have been tested against chronic
      hepatitis B virus (HBV) infection, but trials were unsuccessful or accompanied by
      toxicity. Recently, oral second-generation nucleoside analogues have been
      developed that have potent activity against HBV. The best-studied compound so far
      is lamivudine ((-)2'-deoxy-3'-thiacytidine; 3TC). Lamivudine is an inhibitor of
      reverse transcriptase (RT) activity and is in clinical use in human
      immunodeficiency virus (HIV)-infected individuals. As several studies on the use
      of lamivudine for hepatitis B show, the development of resistance in the viral
      polymerase under lamivudine treatment, however, causes a significant clinical
      problem. All other drugs in advanced clinical development for HBV are
      nucleosides; cross-resistance is therefore expected in most cases. The history of
      HIV treatment demonstrates that new classes of drugs, the protease inhibitors and
      non-nucleosidic inhibitors of RT, allowed for a longer-term clinical benefit when
      used in combination with nucleoside analogues. The development of non-nucleosidic
      compounds with different modes of action therefore appears very important for the
      treatment of chronic hepatitis B as well.

PMID- 10885830
TI  - Fungal resistance.
AB  - Fungal resistance is caused by an acquisition of intrinsically resistant species,
      by selection of resistant strains from a population or by mutation of an
      initially susceptible strain. According to different classes of antimycotics
      there are different resistance mechanisms: differences in the uptake mechanisms,
      drug target alterations, mostly the ergosterol-biosynthesis pathway, and the
      efflux or pumping mechanisms to the outside.

PMID- 10885831
TI  - Drug resistance in Plasmodium falciparum malaria.
AB  - Four classes of drugs are reviewed: blood schizontocides acting only on the
      hemoglobin-digesting blood stages, the antifolates which attack tetrahydrofolate
      synthesis in all the growing stages, antimitochondrials affecting synthesis and
      electron transport, and 8-aminoquinolines which interfere with redox processes.
      Drug efflux via a multidrug resistance membrane protein, and the production of a
      protein competing with the drug for the target hemin are thought to be
      responsible for resistance to blood schizontocides. Structural changes in target
      enzymes are responsible for easily-developed resistance to antifolates and
      antimitochondrials. The judicious use of drug combinations can help to avoid
      development of resistance and combat resistant infections, but new drugs are
      urgently needed.

PMID- 10885832
TI  - Neonatal nosocomial infection surveillance: incidences by site and a cluster of
      necrotizing enterocolitis.
AB  - Nosocomial infection (NI) was prospectively studied in hospitalized neonates
      during a 10-month period. The Centers for Disease Control (CDC) criteria (some
      specified for neonates) were used for surveillance. Forty-nine of 677 infants
      experienced 73 episodes of NI. The overall incidence was 10.8 NI/100 patients and
      6.5 NI/1,000 patient days. The average monthly NI number did not correlate with
      patient load. Very low birth weight (VLBW) infants showed a higher NI incidence
      (81.8 NI/100 patients and 11.1 NI/1,000 patient days), also elevated if adjusted
      for their inherently longer neonatal intensive care unit (NICU) stay. The most
      common NI sites in the VLBW stratum were sepsis and necrotizing enterocolitis
      (NEC), the latter occurring in a seasonal cluster. It can be concluded that
      surveillance for NIs should focus on VLBW infants and include the evaluation of
      NEC, as it behaves like a nosocomial disease.

PMID- 10885833
TI  - Usefulness of clinical scores to predict outcome in bacterial meningitis.
AB  - The predictive usefulness of clinical scores in patients with acute bacterial
      meningitis was investigated. Fifty-one consecutive patients with acute bacterial
      meningitis were scored on days 1, 3, 5, 8, and 14 after admission according to
      the Sandinavian Stroke Scale (SSS), Glasgow Coma-Scale (GCS) and Hunt & Hess
      Scale (HH). As an index of their usefulness to predict the outcome, the scales
      were correlated with short-term outcome on day 21 assessed by the Glasgow Outcome
      Scale (GOS). The scores of all three scales correlated highly significantly with
      short-term outcome. Depending on the day of assessment, Spearman correlation
      coefficients ranged between 0.52 and 0.88 for SSS, between 0.50 and 0.84 for GCS,
      and between -0.47 and -0.82 for HH. The scales differed in their ability to
      predict outcome on and after day 1: mortality was best predicted by GCS, and
      complete recovery was best predicted by SSS. The use of scales in bacterial
      meningitis provides a rational quantitative basis to predict outcome more
      graduated than in dead or alive. Because the scales accentuate different aspects
      of outcome (e.g. mortality, restitution), the selection of a scale to be used in
      clinical trials should take into consideration the main focus of the study.

PMID- 10885834
TI  - Endothelin-1 is elevated in the cerebrospinal fluid of HIV-infected patients with
      encephalopathy.
AB  - In a cross-sectional, non-randomized, prospective study in an outpatient clinic a
      possible relationship between the cerebrospinal fluid (CSF) concentrations of the
      potent vasoconstrictor peptide endothelin-1 (ET-1) and prevalence and degree of
      HIV-encephalopathy was studied. Forty-eight CSF samples from HIV-infected
      patients undergoing lumbar punction for diagnostic reasons were investigated for
      ET-1 concentrations. In 37 patients ET-1 was also measured in plasma. Patients
      were investigated clinically and staged with respect to HIV encephalopathy.
      Patients with arterial hypertension, diabetes or acute opportunistic infections
      were excluded from the study. In the remaining, 18 of the CSF samples were from
      patients with normal neurological findings (grade 0-0.5), whereas 30 were from
      patients with HIV encephalopathy (grade 1-3). The mean CSF ET-1 concentration was
      significantly elevated (P = 0.001) in patients with HIV encephalopathy (1.97 +/-
      2.33 pmol/l) as compared to those patients without encephalopathy (0.57 +/- 0.67
      pmol/l). Moreover, there was a significant correlation between ET-1 CSF
      concentrations and the degree of HIV encephalopathy (r = 0.49, P < 0.001). In
      addition, there was a significant correlation between ET-1 levels in the CSF and
      the IgG serum to CSF ratio. However, we found no correlation between HIV
      encephalopathy and neither CSF total protein, IgG, albumin or the serum to CSF
      ratio of IgG or albumin. In conclusion, we could demonstrate a close relationship
      between CSF ET-1 concentrations and the degree of HIV encephalopathy. Thus, by
      virtue of its long-lasting and potent vasoconstrictor activity ET-1 might
      contribute to the pathogenesis of HIV encephalopathy.

PMID- 10885835
TI  - Hepatitis virus-related and ethanol-induced chronic liver disease with or without
      cryoglobulins--is there a difference concerning clinical or laboratory
      manifestation?
AB  - Mixed cryoglobulinemia is frequent in southern Europe and attributed to hepatitis
      C infection. We analyzed prevalence and clinical symptoms of mixed
      cryoglobulinemia in our region among patients with chronic hepatitis C (n = 29)
      and B (n = 7) in comparison to alcoholic liver cirrhosis without evidence of
      hepatitis virus infection (n = 10). Cryoglobulinemia was found in 13/29 patients
      with hepatitis C (11 type III, one type I1-III and one type II), 2/7 with
      hepatitis B (one type II, one type III) and 4/10 with alcoholic liver cirrhosis
      (one type II, three type III). Patients with moderate active hepatitis had more
      type II than type III cryoglobulins. Concerning clinical symptoms, only sicca
      syndrome was more frequent in patients with hepatitis C. Rheumatoid factor (RF)
      and immune globulin M (IgM) levels were higher in hepatitis C than in the other
      groups. Renal disease was rare in all but not different between the groups. Mixed
      cryoglobulinemia in hepatitis C (and B) is most frequently of type III. Patients
      with hepatitis C had the same prevalence of cryoglobulins as patients with
      alcoholic liver cirrhosis. Cryoglobulins had no influence on clinical syndromes
      or organ damage.

PMID- 10885836
TI  - Helicobacter pylori--a trigger of reactive arthritis?
AB  - Four cases of reactive arthritis (ReA) related to Helicobacter pylori (HP) are
      presented. These were identified by IgG, IgM and IgA ELISA tests performed on
      sera obtained from a 2-year prospective study on 186 patients with a clinical
      picture suggesting ReA as a possible diagnosis. If anti-HP IgM and IgA or IgG
      were positive, the case was considered related to HP. Three out of four HP ReA
      patients were originally classified as "possible ReA", i.e. having a clinical
      picture of ReA but without any identified triggering microorganism. IgG
      antibodies against cagA and vacA were detected in three and two cases
      respectively. The HP ReA patients did not present with typical clinical or
      laboratory features differentiating them from ReA induced by Chlamydia
      trachomatis (N = 25) or enteropathogenic bacteria (N = 27). However, compared to
      findings in patients with ReA due to enteropathogenic bacteria the number of
      active joints was higher (six versus two), duration of arthritis longer (3.9
      weeks versus 2 weeks) and the CRP (C-reactive protein) lower (43 versus 59). Our
      findings suggest that HP may be included in the list of possible arthritis
      triggering microbes.

PMID- 10885837
TI  - Prevalence of hepatitis A antibodies in a large sample of Belgian health care
      workers.
AB  - Health care workers (HCW), especially women (for example, pediatric nurses and
      day nursery workers), have been shown to be at risk for viral hepatitis A
      infections. In order to obtain a more precise estimate of the risk in Belgian
      HCW, a seroprevalence study was undertaken. The data from this study have been
      compared with the age-specific seroprevalence of anti-HAV in the general
      population (GP) as recently estimated. During 1996-1997, a sample of 5,068
      employees in 22 general hospitals, geographically distributed over the Flemish
      and Brussels regions of Belgium, was tested for the presence of anti-HAV.
      Comparison of the anti-HAV prevalences in HCW and GP shows a significantly lower
      prevalence in HCW for the age groups 25-34, 35-44 and 45-54 years. Within these
      age-groups, employees performing catering tasks have the highest prevalence. This
      difference could be explained by socioeconomic parameters: overrepresentation of
      higher social classes in better educated HCW. The number of unprotected
      individuals in young and older age groups (25-54 years) is greater than in the
      general population. In view of the changing HAV epidemiology in western Europe,
      the number of unprotected persons will rise in the coming years. Considering the
      more severe course of the disease as age increases, vaccination may become
      important in the occupational health strategy for HCW.

PMID- 10885838
TI  - Streptococcal toxic shock syndrome in two patients infected by a colonized
      surgeon.
AB  - The incidence of severe invasive infections caused by Streptococcus pyogenes, a
      group A streptococcus (GAS), has increased in the past 10 years. Most cases occur
      outside of the hospital setting. We report on two patients with nosocomial
      streptococcal toxic shock syndrome (StrepTSS). In patient 1 the syndrome was
      associated with the development of necrotizing fasciitis following inguinal
      hernia repair. Patient 2 suffered from StrepTSS shortly after receiving a tetanus
      vaccine in her left deltoid. Epidemiologic investigations of these cases, which
      were noted within 48 hours of each other, showed that the same surgeon performed
      the vaccination on patient 2 after assisting a colleague during the hernia repair
      procedure on patient 1. He was found to be a nasal carrier of GAS. All GAS
      isolates from the patients and the surgeon were indistinguishable by pulsed field
      gel electrophoresis. PCR analysis demonstrated the presence of streptococcal
      pyogenic exotoxins A and F. All strains were of the T-1 serotype and possessed
      the gene for M-protein 1. This report demonstrates that a virulent strain of GAS
      may be spread by asymptomatically colonized medical personnel via the air route.

PMID- 10885839
TI  - Invasive meningococcal disease: patient and strain characteristics set new
      challenge for prevention and control.
AB  - Differences in the course of invasive meningococcal disease, in prevalence, case
      to-carrier ratio, geographical pattern, age distribution and antibiotic
      resistance have been related to major serogroups and their serotypes. The
      relationships between Neisseria meningitidis serogroups and clinical
      manifestation, outcome and patient characteristics are assessed. All hospitalized
      patients in six major hospitals in central Israel with a verified meningococcal
      disease during 1990-1994 were included (n = 66). Their personal and clinical data
      and the results of bacteriological and serological tests of their blood and
      cerebrospinal fluid (CSF) were recorded. Meningococci were isolated from both
      blood and CSF, from blood alone, and from CSF alone in 60.6%, 18.2%, and 21.2% of
      the cases, respectively. The highest proportion of isolations were from infants <
      1 year (34.8%), followed by children aged 1 to 5 years (25.8%). Serogroup B
      prevailed in 62.1%, while groups C and W135 accounted for 28.8% and 9.1%,
      respectively. Serogroup B predominated in children < 1 year, while in patients
      aged 5-22 years, C strains were the major pathogen (P < 0.001). Serogroup B
      accounted for 93% of the cases of meningitis, 58% of meningococcemia and 42% of
      fulminant meningococcemia, while group C strains were the major cause of
      fulminant meningococcemia (50%). The overall case fatality rate was 7.6%:
      fulminant meningococcemia 8.3%, and meningococcemia 10%. It was concluded that N.
      meningitidis group C continues to account for almost a third of the cases of
      meningococcal disease and is the major cause of fulminant meningococcemia.

PMID- 10885840
TI  - Antimicrobial susceptibility of 1,422 Haemophilus influenzae isolates from
      respiratory tract infections in Spain. Results of a 1-year (1996-97) multicenter
      surveillance study. Spanish Surveillance Group for Respiratory Pathogens.
AB  - A Haemophilus influenzae multicenter antimicrobial susceptibility surveillance
      was carried out. An overall beta-lactamase production rate of 25.7% was found,
      with significant differences between hospitals ranging between 7.9 and 47.9%.
      Presumable intrinsic resistance was found in 4.6% of strains. No differences in
      susceptibility were observed between beta-lactamase positive and beta-lactamase
      negative strains for all antibiotics, except for penicillin, amoxicillin and
      cefaclor. A higher prevalence of resistance was found for clarithromycin vs
      azithromycin (22.6 vs 0.7%). Differences in all these factors make surveillance
      essential as a guideline for empiric treatment in community-acquired respiratory
      tract infections.

PMID- 10885841
TI  - Optimal tobramycin dosage in patients with cystic fibrosis--evidence for
      predictability based on previous drug monitoring.
AB  - A retrospective analysis of files of patients with cystic fibrosis and pulmonary
      exacerbations was performed to investigate whether an individual dosage of
      tobramycin once established by serum level determination allows a reliable
      prediction of the adequate dosage in a consecutive exacerbation. All patients
      hospitalized > or = 2 times between May 1997 and September 1998 with pulmonary
      exacerbation due to Pseudomonas aeruginosa infection susceptible to tobramycin
      were included. The initial dosage to tobramycin was 5 mg/kg body weight every 12
      h followed by drug level determinations to establish the optimal dose. In a
      consecutive exacerbation the same dosage per kg body weight was used again and
      drug level determinations were repeated. Sixteen patients (six female = 38%) with
      a mean age of 24 years (median: 26 years, range: 9-33) were hospitalized for 49
      pulmonary exacerbations (2-6 per patient, mean: 3, median: 2.5). During the first
      episode of tobramycin treatment in the study period all trough levels were < 2
      microg/ml (median: 0.6) and the peak levels were 7.1-16.9 microg/ml (median:
      11.9). In four patients the peak level was > 12 microg/ml. In 28 consecutive
      episodes the dosage of tobra myci n was chosen based on optimal results of
      previous drug level monitoring and in 27 instances (96%) the previously
      established optimal dose was confirmed. In five consecutive episodes the
      tobramycin dosage had been increased erroneously and this resulted in abnormally
      high peak levels in three cases. These findings suggest that a safe and
      therapeutic tobramycin dosage in an individual patient with cystic fibrosis is
      predictable based on a previously established optimal dosage.

PMID- 10885842
TI  - Circulating cytokine concentrations in tuberculosis and other chronic bacterial
      infections.
AB  - Cytokines are a group of hormone-like polypeptides that play a variety of
      regulatory roles in host defense against infection. Because of the possible
      different involvement of these mediators in bacterial infections and
      tuberculosis, enzyme immunoassay was used to measure comparatively the plasma
      levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), tumor
      necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and interferon gamma (IFN
      gamma) in 25 immunocompetent patients divided into two groups: in 12 patients
      clinical and microbiological diagnosis showed a chronic bacterial infection and
      13 patients had pleuropulmonar tuberculosis. After resolution of the infectious
      disorders (> or = 3 months), these measurements were repeated for each patient.
      High levels of IL-1b, TNF-alpha and IL-6 were observed at study entry, but no
      significant difference was found between the groups. In contrast, plasma levels
      (mean +/- SEM) of IFN-gamma were significantly higher in patients with
      tuberculosis when compared with the bacterial group (0.753 +/- 0.201 vs 0.325 +/-
      0.105 IU/ml; P = 0.020). This different pattern of plasma proinflammatory
      cytokines could be ascribed to a prevaling role of the mediators of so-called Th
      1 immune response (IFN-gamma) in host defense against infection with
      Mycobacterium tuberculosis.

PMID- 10885843
TI  - Isolation of Borrelia afzelii from overwintering Culex pipiens biotype molestus
      mosquitoes.
AB  - During the years 1995-1996, a total of 1,743 overwintering Culex pipiens biotype
      molestus female mosquitoes were tested for the presence of spirochetes in several
      localities in South Moravia, Czech Republic.The spirochetes were observed in 5%
      of the mosquitoes investigated. One of the five isolated strains of spirochetes
      (BR-84) was identified as Borrelia afzelii. The potential role of mosquitoes in
      the ecology and epidemiology of Lyme disease (LD) borreliae should be further
      investigated.

PMID- 10885844
TI  - Diagnosis of Cardiobacterium hominis endocarditis by broad-range PCR from arterio
      embolic tissue.
AB  - A case of culture-negative endocarditis is reported, in which the diagnosis of
      Cardiobacterium hominis endocarditis was made from arterio-embolic tissue removed
      by percutaneous transluminal embolectomy by broadrange polymerase chain reaction
      amplification of the 16 rRNA gene, followed by single-strand sequencing. The use
      of this technique to identify etiologic agents from arterio-embolic material has
      not been reported so far. A serologic assay employing complement fixation against
      a crude antigen of Cardiobacterium hominis confirmed the diagnosis of
      endocarditis caused by this unusual fastidious etiologic agent.

PMID- 10885845
TI  - Diagnosis by polymerase chain reaction of pneumonia caused by Legionella
      pneumophila in an immunocompetent child.
AB  - A 10-year-old, previously healthy child with pneumonia caused by Legionella
      pneumophila diagnosed by polymerase chain reaction (PCR) of serum is presented.
      Diagnostic methods were PCR of serum using two different primer sets, and the
      detection of specific antibody in paired sera using an indirect
      immunofluorescence assay. Legionella DNA was amplified from serum obtained before
      and on day 6, but not after completion of a 14-day course of oral clarithromycin.
      The etiologic role of L. pneumophila was confirmed by seroconversion. The report
      illustrates that L. pneumophila PCR of serum may contribute to the identification
      of this microorganism as a cause of severe pneumonia in immunocompetent children.

PMID- 10885846
TI  - Duke criteria-negative endocarditis caused by Bartonella quintana.
AB  - Bartonella spp. were recently recognized as causative agents of culture-negative
      endocarditis. Molecular techniques, such as broad-range PCR, are now available to
      detect fastidious or slow-growing microorganisms, or those which cannot be
      cultured. Such microorganisms may be responsible for culture-negative
      endocarditis. Alcoholism and homelessness are known risk factors for Bartonella
      quintana endocarditis, even in patients without previous valvular disease. We
      report a case of B. quintana endocarditis diagnosed by PCR amplification on the
      excised heart valve, in a young non-alcoholic and immunocompetent patient with
      few clinical signs of infection who did not fulfill the Duke criteria.

PMID- 10885847
TI  - Lyme arthritis in a 12-year-old patient after a latency period of 5 years.
AB  - Lyme arthritis (LA) may be confused with other rheumatic diseases, particularly
      in the absence of a history of erythema migrans (EM). We report the case of a 12
      year-old patient who developed a large effusion of the right knee joint. The
      titer for antinuclear antibodies was 1:80 and the test for rheumatoid factor was
      negative. Investigations for antibody response to Borrelia burgdorferi
      demonstrated remarkable elevation of IgG antibody and no specific IgM response.
      These results were confirmed by immunoblotting reactivity with the bands p83/100,
      p58, p43, p41, p39, OspA, p30, OspC, p21, and p17. We subsequently learned that
      the child had suffered a tick bite followed by an EM 5 years earlier and had been
      treated with trimethoprim/sulfamethoxazole at that time. The patient now was
      given intravenous ceftriaxone, 2 g daily for 14 days. In the absence of clinical
      improvement 3 weeks later a knee joint aspiration was performed which resulted in
      a positive polymerase chain reaction (PCR) test for B. burgdorferi DNA (OspA) in
      the synovial fluid. The patient fully recovered 2 months later without further
      treatment. The case indicates that the latency period between EM and onset of LA
      may last up to 5 years. In addition to serologic test methods, analysis of
      synovial fluid using PCR may be decisive for making the final diagnosis of LA.

PMID- 10885849
TI  - Scrub and murine typhus among Dutch travellers.

PMID- 10885848
TI  - Intestinal tuberculosis presenting as fever of unknown origin in a heart
      transplant patient.
AB  - Patients undergoing transplantation have an increased risk of developing
      infections such as tuberculosis, Pneumocystis carinii pneumonia, Candida
      infections or cytomegalovirus infections because of their immunosuppressive
      therapy with cyclosporin A, azathioprine and steroids. Mycobacterial infection is
      well recognized as a complication in the immunocompromised host but diagnosis and
      therapy are very difficult.

PMID- 10885850
TI  - Subcutaneous nodules as presenting sign of disseminated BCG infection in a SCID
      patient.

PMID- 10885851
TI  - Trends in the epidemiology of herpes simplex virus type 1 among the young adult
      population in Israel.

PMID- 10885852
TI  - Frequent detection of TT virus in throat swabs of pediatric patients.

PMID- 10885853
TI  - Pharmacokinetic and clinical evaluation of serious infections in premature and
      newborn infants under therapy with imipenem/cilastatin.
AB  - Efficacy and pharmacokinetic parameters of imipenem/cilastatin (I/C) were
      investigated in a retrospective evaluation in 104 premature and newborn infants.
      Patients enrolled in this investigation constituted a particularly high risk
      group with extreme prematurity, perinatal asphyxia and amnion infection as well
      as various malformations. In 15 of the 104 infants serum concentrations were
      measured for drug monitoring and determination of optimal total daily dosage. A
      total daily dose of 50 mg/kg birth weight for premature and newborn infants
      divided into two doses led to imipenem peak concentrations of 17.7 mg/l +/- 9.2
      mg/l (range: 1.95-38.05) and trough levels were 2.35 mg/l +/-1.02 (range 2.34
      10.88) in premature infants. Imipenem peak concentrations of 20.6 +/- 10.8 (range
      3.94-32.3) and trough levels of 0.43 +/- 0.17 (range 0.16-0.94) were measured in
      newborns. The half-life of elimination was 3.3 h and 1.86 h, respectively. Six of
      the 104 treated patients died, five of them of causes unrelated to infection.
      Seizures occurred in 8.9% of patients during therapy with I/C compared with 5.8%
      of a large survey of premature and newborn infants in our intensive care unit
      (ICU). However, the severity of illness of these two groups cannot be compared.
      I/C can be expected to constitute effective therapy in premature and newborn
      infants with serious nosocomial infections even after failure of other broad
      spectrum antibiotics.

PMID- 10885854
TI  - Gompertzian growth as a self-similar and allometric process.
AB  - The Gompertz law of growth has puzzled scientists for decades: while it
      successfully described growth kinetics of various biological systems (e.g., tumor
      growth), its foundation has remained unclear. In this paper I recognize the
      Gompertzian growth as founded on self-similarity, which is so abundant in natural
      phenomena that it justifiably represents a fundamental natural paradigm. The self
      similarity leads to an allometric principle: the sizes of a given biological
      system at different times are related by a simple power law. The stated relation
      can be also viewed as basic functional growth equation with unique nonconstant
      solutions being the Gompertz and the exponential functions. This equation also
      provides the description of growth and regression dynamics in terms of a
      difference equation which already has found practical application in
      characterizing tumor growth kinetics.

PMID- 10885855
TI  - Growth and behavioral development in plasminogen gene-targeted mice.
AB  - The plasminogen system, in addition to its major role in fibrinolyis, is believed
      to play a key role in development of the nervous system. The purpose of this
      study was to directly examine and quantify the importance of plasminogen in
      physical and behavioral development in plasminogen deficient mice (Plg-/-),
      plasminogen heterozygous mice (Plg+/-), and wild-type mice (Plg+/+, WT) at 2-21
      days of age. Remarkably, little difference in growth and behavioral development
      was observed between Plg-/- and WT mice. Body weight gain and the milestones of
      physical development-ear detachment, eye opening and teeth eruption were similar
      from 2-21 days of age. Differences were found in physical development only after
      4 wks of age, body weight gain was less and vaginal patency was delayed in the
      Plg-/- mice compared to WT mice. Behaviors, assessed during the 2-21 days of age
      period, developed in the Plg-/- mice in a pattern similar to WT mice.
      Specifically, no differences were found between Plg-/- and WT mice in the
      development of reflexes, neuromotor ability, motor coordination, locomotor
      activity, reaction to gravitational positioning, integration of motor and
      vestibular systems, olfactory development, and incidence of audiogenic seizure
      susceptibility. However, Plg-/- mice demonstrated a faster surface righting
      response and a faster latency for audiogenic seizure susceptibility, as well as
      an increase in the number of grooming bouts at age 17-21 days. These differences
      indicate that a plasminogen deficiency alters reactivity and the response to
      stress. The weight of the pituitary was smaller and pituitary and plasma
      corticotrophin releasing hormone were elevated in the Plg-/- mice compared to the
      WT mice. The results of this study suggest a role for the plasminogen system in
      hormone processing and neuroendocrine regulation.

PMID- 10885856
TI  - Growth and muscle characteristics of a growth selected line of Japanese quail
      (Coturnix coturnix japonica), a control line and reciprocal crosses between them.
AB  - Body growth, muscle growth, bone growth, and measurements of muscle fiber area
      and fiber number were made in a line of Japanese quail (Coturnix coturnix
      japonica) selected for high 4 week body weight for 100 generations (line PP), in
      the control line from which they were derived (line CC), and in genetically
      equivalent reciprocal crosses (PC and CP) that develop in eggs that differ
      greatly in weight. There was no difference in body weight or weight of the P.
      superficialis of newly hatched CC or PC quail. Weights of PP and CP were equal to
      each other but greater than those of CC and PC. Body and muscle weights of the
      crosses were equal by 3 to 4 weeks of age. The number of fibers in the
      Semimembranosus muscle was lowest in CC quail, intermediate in PC and CP quail,
      and greatest in PP. Cross-sectional area of Semimembranosus fibers from 7 day old
      CC and PC were equal to each other and smaller than those of PP or CP quail. By
      29 days of age, fibers in CC were smallest, those in PC and CP were intermediate
      and smaller than those of PP quail. At 7 days, the cross-sectional area of P.
      superficialis fibers of CP quail was greater than those of the other genotypes,
      but by 14 days and after fiber area was directly related to the bird's genetic
      potential for growth. These studies show that fiber hyperplasia is genetically
      determined whereas fiber hypertrophy in early life is primarily dependent on the
      dam's genotype and egg environment.

PMID- 10885857
TI  - Mathematical modeling of human embryonic and fetal growth rates.
AB  - A mathematical model for human embryonic/fetal growth data from implantation to
      birth is developed. In previous work, it was shown that an unbiased estimate for
      human fetal growth data from about day 50 post-conception until term could be
      calculated from the Gompertz equation. This period represents a range of
      embryonic/fetal weights from one to 3500 g. When the Gompertz equation is
      extended, with no change of parameters, to the prenatal period before 50 days,
      the predicted weights have a consistent bias which might have a biological basis.
      Early embryonic growth immediately following fertilization is exponential; i.e.,
      one cell goes to 2, then 4, then 8... etc., with essentially no decrease in
      relative growth rate. Except for possible small changes in cell size and cell
      mitosis cycle time, such exponential growth can be considered as a special case
      of the Gompertz equation with a, the relative rate of decrease of the relative
      growth rate, equal to zero. The relative growth rate begins to decrease about 20
      days post-conception, at the time of cell differentiation into organ precursors.
      Although the "Hayflick Limit" of the maximum of 50 to 60 cell divisions for human
      cells would tend to cause a decrease in growth rate, it can be shown that the
      effect is insignificant during embryonic/fetal growth. The observed decrease in
      the growth rate might be a result of a decreasing fraction of cells in the pool
      of dividing cells. For the Gompertz equation model, a at this time changes from
      zero to a positive number. Analysis of fetal growth data shows that a rapidly
      becomes large and then decreases over a period of several days to become a
      constant positive value for the remainder of the prenatal term. Good fits of
      empirical embryonic/fetal growth data were obtained by nonlinear regression with
      calculation of the embryonic/fetal weights through numerical integration of the
      differential Gompertz equations and the functionality of alpha.

PMID- 10885858
TI  - The effect of ageing on nutrient digestibility by cats fed beef tallow-,
      sunflower oil- or olive oil-enriched diets.
AB  - Nutrient digestibility and absorption decline with age in several mammalian
      species. The aim of this study was to compare apparent fat digestibility of
      different dietary fats in young and senior cats. Three diets enriched with either
      beef tallow (high in saturated fatty acids), olive oil (high in monounsaturated
      fatty acids) or sunflower oil (high in polyunsaturated fatty acids) were fed to 6
      young (3.0+/-0.9y) and 6 senior (11.6+/-1.4y) cats at 300kJ metabolisable
      energy/kgBW0.75/d in a 3*3 Latin square design. Food and faecal samples collected
      over two consecutive 7d periods were analysed for fat, protein, moisture, ash,
      gross energy and fatty acid content. Apparent digestibilities of fat and energy
      were significantly lower (P=0.03) in senior cats compared to young cats (fat:
      0.922 compared to 0.944; energy: 0.848 compared to 0.885, for senior and young
      cats, respectively) in all three diets. Senior cats exhibited a lower apparent
      digestibility for all fatty acid groups compared to the younger cats (saturated:
      0.932 compared to 0.952; monounsaturated: 0.964 compared to 0.982;
      polyunsaturated: 0.980 compared to 0.987, for senior and young cats,
      respectively). Saturated fatty acids had the lowest apparent digestibility in
      both young and senior cats, and shorter chain fatty acids were digested more
      easily than the longer chain fatty acids. These results suggest that the age
      related reduction in apparent fat digestibility was a general phenomenon
      affecting all fatty acids, and was not due to one particular fatty acid group.

PMID- 10885859
TI  - What works in dementia care? Research evidence for policy and practice: part I.

PMID- 10885860
TI  - What do service planners and policy-makers need from research?
AB  - Nine policy preoccupations have been identified in a recent study of dementia
      care policies in all European countries. These are used to structure a set of
      issues which researchers might usefully address to assist service planners and
      policy-makers. Areas where there is already a research literature are identified.
      Some description and commentary on the application of current policies in the UK
      is provided to illustrate the need for research. It is suggested that service
      planners and policy-makers march to some distant drum which is only remotely
      related to research, if at all. However, the importance of a research base is
      stressed with the suggestion that research in related fields could usefully be
      transferred.

PMID- 10885861
TI  - Promoting well-being and independence for people with dementia.
AB  - This paper reviews the research evidence relating to non-pharmacological
      interventions with people with dementia aiming to improve well-being and
      independence. There have been a number of attempts to improve the person's level
      of independent functioning through programmes training and supporting self-care
      skills, mobility, continence, orientation and participation in activities. Well
      being has been less often directly addressed, although recently studies have
      begun to specifically target aspects of it. Increased independence does not
      necessarily lead to greater well-being, and it is clear that the greatest
      potential for increasing function is in tackling the excess disability which many
      care giving situations in effect impose on the person with dementia. In carrying
      out research in this area, the limitations of randomized controlled trials are
      evident, and there is much to be said for the reporting of series of carefully
      controlled single-case studies in addition to group studies. Further development
      of methods of measuring well-being in people with dementia is also required.

PMID- 10885862
TI  - Training families to provide care: effects on people with dementia.
AB  - This paper addresses four questions concerning family training in dementia care:
      (1) What do we know about what works? (2) How do we know it? (3) What do we now
      need to know? (4) How should we go about trying to find this out? In addition, it
      provides some introductory information on the nature of family caregivers in
      dementia and the phenomenology of caregiver burden and behavioral problems in
      dementia, often the focus of family training. Training families to provide care
      to dementia patients has a long clinical history. In recent years, the amount and
      popularity of this kind of information has grown exponentially, as is evident in
      the proliferation of books, training materials and informational handouts. Even
      video and world wide web technology is now used to educate caregivers. Over a
      decade ago, reports showed that caregivers were able to learn specific behavioral
      techniques and successfully reduce problematic behaviors. More recently,
      controlled trials have suggested the effectiveness of caregiver training programs
      in reducing behavioral problems or delaying institutionalization in patients with
      dementia. There is much still unknown concerning family training in dementia
      care. Additional controlled clinical trials are needed, as are additional studies
      to understand the broader factors known to influence effective care, such as
      patient and caregiver physical health or family and social supports.

PMID- 10885863
TI  - Eliciting user perspectives on what works.
AB  - Social care research has moved gradually in recent years to include the
      subjective perspective. Dementia care, which in many ways is still in its
      infancy, has lagged behind in this development, and much research has been
      informed by the carer rather than the person with dementia. As a young subject
      area, it is right that dementia care should look around for lessons that can be
      learned from other disciplines. This paper will consider how research with people
      with learning difficulties has developed a culture for hearing the views of
      service users. It will outline various methodologies, with considerations of
      their strengths and weaknesses. The paper will then review research in dementia
      care which features the subjective experience, and will finally draw out lessons
      and identify possible ways forward.

PMID- 10885864
TI  - Memantine in severe dementia: results of the 9M-Best Study (Benefit and efficacy
      in severely demented patients during treatment with memantine).
AB  - OBJECTIVES: To assess clinical efficacy and safety of memantine--an uncompetitive
      N-methyl-D-aspartate (NMDA) antagonist--in moderately severe to severe primary
      dementia. MATERIALS AND METHODS: Dementia was defined by DSM-III-R criteria and
      severity was assessed by the Global Deterioration Scale (stages 5-7) and the Mini
      Mental State Examination (< 10 points). Primary endpoints were the Clinical
      Global Impression of Change (CGI-C) rated by the physician, and the Behavioural
      Rating Scale for Geriatric Patients (BGP), subscore 'care dependence', rated by
      the nursing staff. Secondary endpoints included the modified D-Scale
      (Arnold/Ferm). RESULTS: The ITT sample comprised 166 patients and 151 patients
      were treated per protocol. At 12-week ITT endpoint analysis, 82 received
      memantine 10 mg per day, 84 placebo. Dementia was in 49% of the Alzheimer type
      and in 51% of the vascular type (CT, Hachinski score). A positive response in the
      CGI-C was seen in 73% versus 45% in favour of memantine (stratified Wilcoxon p <
      0.001), independent of the etiology of dementia. The results in the BGP subscore
      'care dependence' were 3.1 points improvement under memantine and 1.1 points
      under placebo (p = 0.016). A coincident response of the two independent target
      variables was observed in 61.3% (memantine) versus 31.6% (placebo). Secondary
      endpoint analysis of the D-Scale assessing basic ADL functions support the
      primary results. Regarding the safety profile, no significant differences between
      treatment groups were observed. CONCLUSIONS: The results of this trial support
      the hypothesis that memantine treatment leads to functional improvement and
      reduces care dependence in severely demented patients.

PMID- 10885865
TI  - Assessment approaches for older people receiving social care: content and
      coverage.
AB  - BACKGROUND: Assessment was identified as one of the 'cornerstones' of community
      care. This study presents findings from the first nationally representative
      analysis of assessment documents used by social services agencies in the UK.
      METHOD: In this paper analysis is made of 50 assessment documents used for the
      'comprehensive' assessment of older people. The documents were examined in the
      extent to which they covered 33 assessment domains, grouped into four areas:
      functional domains; cognitive, mood and psychosocial domains; social environment
      domains; and clinico-medical domains. The documents were analysed on three
      dimensions: whether the domains were covered at all; whether the domain was
      covered in sufficient detail; and whether it would elicit a structured response.
      RESULTS: Activities of daily living were covered to some extent on the majority
      of documents, as were the instrumental activities of daily living. Very few
      documents were designed to elicit information on the potential for
      rehabilitation. Whilst the majority of forms were designed to collect some
      information on cognitive patterns, mood state and social activity, very few were
      designed to collect this in any detail. Although functional activities of daily
      living were covered in greater detail than the other domains overall, there was
      enormous variability between the documents, thus hampering their ability to
      generate any standardized information.

PMID- 10885866
TI  - Current awareness in geriatric psychiatry.

PMID- 10885867
TI  - The rise and rise of asthma: a new paradigm for the new millennium?

PMID- 10885868
TI  - A hundred years of population genetics theory.

PMID- 10885869
TI  - Ethics in epidemiology: common misconceptions, paradoxes and unresolved
      questions.

PMID- 10885870
TI  - Epidemiology of cancer with a focus on Europe.

PMID- 10885871
TI  - Environment and health: the long journey of environmental epidemiology at the
      turn of the millennium.

PMID- 10885872
TI  - Epidemiologic studies of alcohol-related disease in the 20th century.
AB  - During the 20th century alcohol and alcoholism have emerged as a problem with
      global health implications. In Westernized countries > or = 50% of adults can be
      classified as alcohol consumers. For most people, drinking is a safe, pleasurable
      experience with minimal health consequences. However, about 10% of alcohol
      consumers will at some time experience serious health problems related to their
      drinking habit. Persons at risk of drinking problems cannot be reliably
      identified in the population--a fertile area for additional research. At present,
      the World Health Organization estimates that > 15 million people are disabled as
      a result of alcohol use, making it the fourth leading cause of worldwide
      disability. The challenge for the 21st century is to reduce the impact of alcohol
      related disease by measures including: * Identification of high risk individuals.
      * Social control. * More effective treatment modalities for people addicted to
      alcohol.

PMID- 10885873
TI  - The historical development of epidemiological methods for studying HIV-1 disease
      progression.

PMID- 10885874
TI  - The Colin S. Pittendrigh Lecture. Colin Pittendrigh, Jurgen Aschoff, and the
      natural entrainment of circadian systems.

PMID- 10885875
TI  - Fluorescent differential display identifies circadian clock-regulated genes in
      Arabidopsis thaliana.
AB  - Circadian rhythms in gene expression were first observed in plants more than 13
      years ago, but the underlying mechanism controlling rhythmic gene expression is
      still not understood. The isolation of novel circadian clock-controlled genes
      (ccgs) is likely to provide new tools for studying circadian rhythms. Fluorescent
      differential display (FDD) was used to screen Arabidopsis thaliana mRNAs for
      cycling transcripts. Seventy PCR primer pairs were screened, and 17 different
      cycling bands were observed out of an estimated 10,500 bands screened. The
      identities of 10 bands were determined, and the rhythmic gene expression was
      confirmed using northern blot analysis. The 10 cycling bands represent 7
      different genes, 6 of which are present in the databases and 1 that does not
      match anything in current databases. The rhythmic expression of the 7 genes is
      composed of four distinct phases of clock regulation. The results demonstrate
      that FDD can be used to isolate ccgs. The genes identified in this screen range
      from known A. thaliana ccgs, as well as genes shown to be clock controlled in
      other plant species, to a novel gene that may encode a pioneer protein. Further
      study of these ccgs is likely to increase our understanding of circadian
      regulated gene expression.

PMID- 10885876
TI  - Rhythmic activity of uptake hydrogenase in the prokaryote Rhodospirillum rubrum.
AB  - Growth of Rhodospirillum rubrum was followed in cultures kept under anoxic
      conditions at constant temperature in either continuous light (LL, 32 degrees C)
      or continuous darkness (DD, 32 degrees C and 16 degrees C). In DD, only small
      modifications of the turbidity were detected; linear regression analysis
      nevertheless gives a very significant slope (t(34) = 13.07, p < 10(-14), with R2
      of 0.834). Mean generation times reflected these differences of growth with
      11.9+/-0.5 h in LL and 43.2+/-1.1 h in DD at 32 degrees C and 37.4+/-1.0 h at 16
      degrees C cultures. The uptake hydrogenase (Hup) activity has been followed in
      situ in whole cells of R. rubrum grown in the same conditions, and a clear
      ultradian rhythm of activity has been observed. Indeed, after about 12 h in the
      new media, a rapid rise of hydrogenase activity was observed in both LL and DD
      cultures after which it decreased again to very low values. The activity of Hup
      continued to show such fluctuations during the rest of the experiment, both in DD
      and in LL, during the growth and stationary phases. The Lomb-Scargle power
      periodogram method demonstrates the presence of a clear rhythmic Hup activity
      both in LL and DD. In the LL-grown cultures, the oscillating activity is faster
      and continues throughout the growth and the stationary phases, with an ultradian
      period of 12.1+/-0.5 h. In DD, the slow-growing bacteria showed an ultradian
      oscillatory pattern of Hup activity with periods of 15.2+/-0.5 h at 32 degrees C
      and 23.4+/-2.0 h at 16 degrees C. The different periods obtained for LL- and DD
      grown bacteria are significantly different.

PMID- 10885877
TI  - Circadian rhythms in Neurospora: a new measurement, the reset zone.
AB  - The authors define a new feature of a circadian rhythm, the reset zone, and point
      out its usefulness for predictions concerning oscillator behavior. The reset zone
      measures the responses of a circadian system to resetting pulses. It can be
      easily determined from a phase transition curve (PTC), which is simply a phase
      response curve (PRC) replotted as new phase versus old phase (Winfree's format).
      The reset zone is the range of new phases seen in such a plot and has two
      potentially useful characteristics: its size and its midpoint. A series of
      experiments with Neurospora involving temperature pulses indicated that the size
      of the reset zone changed in a nonlinear way in response to both the duration of
      40 degrees C pulses and to the magnitude of temperature change for 3-h pulses.
      Other existing data are replotted to show how the reset zone size varies with
      growth temperature and with the period of different clock mutants. Employing
      exclusively reset zone data within the framework of a limit cycle displacement
      model, an equation is formulated that predicts the relative changes in the values
      of state variables of the oscillator for changes in any given environmental
      condition, such as temperature. Examples are also drawn from other organisms,
      such as hamsters, Gonyalaux, Kalanchoe, and Drosophila, illustrating the
      usefulness of the reset zone measurement. It can be used as a numerical scale for
      assessing the strength of a pulse, for comparing the relative effects of a given
      pulse applied to different organisms or mutants, for determining the
      directionality of the changes in state variables produced by various types of
      pulses, and possibly for measuring clock amplitude.

PMID- 10885878
TI  - Circadian clock controlling egg hatching in the cricket (Gryllus bimaculatus).
AB  - Adult crickets (Gryllus bimaculatus) were maintained under a 12-h light:12-h dark
      cycle (LD 12:12). After oviposition, their eggs were incubated under different
      lighting regimens at 23 degrees C, and temporal profiles of egg hatching were
      examined. When the eggs were incubated in LD 12:12 or in DL 12:12 with a phase
      difference of 12h from LD 12:12, throughout embryogenesis, 88% to 97% of hatching
      occurred within 3 h of the dark-light transition on days 17 and 18 of
      embryogenesis; the phases of the egg-hatching rhythms in the LD 12:12 and DL
      12:12 groups differed by about 12 h. In eggs incubated in constant darkness (DD)
      throughout embryogenesis, a circadian (about 24 h) rhythm of hatching was found,
      and the phase of the rhythm was similar to that seen in eggs incubated in LD
      12:12, but not DL 12:12, throughout embryogenesis. When eggs that had been
      incubated in DD after oviposition were transferred to DL 12:12 in the middle or
      later stages of embryogenesis and were returned to DD after three cycles of DL
      12:12, the rhythm of hatching synchronized (entrained) to DL 12:12. However, when
      eggs in the earlier stages of embryogenesis were transferred from DD to DL 12:12
      and returned to DD after three cycles, 52% to 94% of hatching did not entrain to
      DL 12:12. To determine whether photoperiodic conditions to which the parents had
      been exposed influenced the timing of egg hatching, adult crickets were
      maintained in DL 12:12, and their eggs were incubated in LD 12:12, DL 12:12, or
      DD throughout embryogenesis. The egg-hatching rhythm was also found in the eggs
      incubated under these three lighting regimens. In DD, the phase of the rhythm was
      similar to that seen in eggs incubated in DL 12:12, not LD 12:12, throughout
      embryogenesis. The results indicate that in the cricket, the timing of egg
      hatching is under circadian control and that the circadian rhythm of hatching
      entrains to 24-h light:dark cycles, but only if the light:dark cycles are imposed
      midway through embryogenesis. Therefore, by midembryogenesis, a circadian clock
      has been formed in the cricket, and this is entrainable to light:dark cycles. In
      addition, the photoperiodic conditions to which the parents (probably the
      mothers) have been exposed influence the timing of hatching, suggesting that
      maternal factors may regulate the timing of egg hatching.

PMID- 10885879
TI  - Modeling the dual pacemaker system of the tau mutant hamster.
AB  - Circadian pacemakers in many animals are compound. In rodents, a two-oscillator
      model of the pacemaker composed of an evening (E) and a morning (M) oscillator
      has been proposed based on the phenomenon of "splitting" and bimodal activity
      peaks. The authors describe computer simulations of the pacemaker in tau mutant
      hamsters viewed as a system of mutually coupled E and M oscillators. These mutant
      animals exhibit normal type 1 PRCs when released into DD but make a transition to
      a type 0 PRC when held for many weeks in DD. The two-oscillator model describes
      particularly well some recent behavioral experiments on these hamsters. The
      authors sought to determine the relationships between oscillator amplitude,
      period, PRC, and activity duration through computer simulations. Two
      complementary approaches proved useful for analyzing weakly coupled oscillator
      systems. The authors adopted a "distinct oscillators" view when considering the
      component E and M oscillators and a "system" view when considering the system as
      a whole. For strongly coupled systems, only the system view is appropriate. The
      simulations lead the authors to two primary conjectures: (1) the total amplitude
      of the pacemaker system in tau mutant hamsters is less than in the wild-type
      animals, and (2) the coupling between the unit E and M oscillators is weakened
      during continuous exposure of hamsters to DD. As coupling strength decreases,
      activity duration (alpha) increases due to a greater phase difference between E
      and M. At the same time, the total amplitude of the system decreases, causing an
      increase in observable PRC amplitudes. Reduced coupling also increases the
      relative autonomy of the unit oscillators. The relatively autonomous phase shifts
      of E and M oscillators can account for both immediate compression and expansion
      of activity bands in tau mutant and wild-type hamsters subjected to light pulses.

PMID- 10885880
TI  - No melatonin suppression by illumination of popliteal fossae or eyelids.
AB  - A recent report that popliteal illumination shifted the circadian rhythms of body
      temperature and melatonin challenged the longstanding belief that light phase
      shifting the circadian system in mammals is mediated only through the retina. The
      authors tested effects of popliteal illumination and illumination provided
      through the eyelids on melatonin suppression. In randomized, counterbalanced
      orders, healthy volunteers received three treatments from midnight until 2:00 AM,
      one on each of three visits to the laboratory. Treatments included (1) no
      illumination from light pads applied to the popliteal fossae, with light mask
      maintained at < 3 lux (control); (2) light mask illuminated at 1700 lux, with
      popliteal light pads extinguished; and (3) popliteal light pads illuminated
      (13,000 lux) and light mask at < 3 lux (control). Saliva specimens were sampled
      at midnight, at 1:00 AM, and at 2:00 AM. Mean salivary melatonin concentrations
      rose from an average of 30.8 (3.9) pg/ml at midnight (baseline), to 33.2 (4.0)
      pg/ml at 1:00 AM, and to 37.2 (3.8) pg/ml at 2:00 AM in all three conditions, but
      no statistical differences were found using repeated-measures ANOVA. No evidence
      of melatonin suppression by either popliteal or closed eyelid light stimulation
      was found. These data suggest that bright retinal illumination is necessary for
      suppression of melatonin mediated through the suprachiasmatic nuclei.

PMID- 10885881
TI  - Long-term trends in exposures to nickel aerosols.
AB  - A comprehensive evaluation of temporal changes in exposure to nickel aerosols in
      the nickel-producing and nickel-using industries was conducted. For various
      nickel compounds, trends in the geometric mean exposure levels were evaluated on
      the basis of job group, building, plant, and industrial sector. At each level of
      classification, approximately two-thirds of the data provided evidence of
      workplace declines in exposures. Depending on how exposure measurements were
      aggregated, approximately one-quarter to one-half of the data produced
      statistically significant trends, with far more exposures declining than
      increasing over time. Whereas significantly negative linear trends were detected
      for total nickel exposures in the mining (-7%/yr), smelting (-9%/yr), and
      refining (-7%/yr) sectors, total nickel exposures in milling showed a
      significantly positive trend (+4%/yr). When the data were classified at the job
      group, building, or plant level, the median rate of change in exposure levels was
      -4, -6, and -3%/yr, respectively. For a subset of the data, effects of various
      factors related to work environment, process, and nature of the job on trends in
      exposure levels were evaluated. When such factors were examined simultaneously,
      the results suggested that the decline in exposures was greater in workplaces
      with no ventilation system compared with ventilated workplaces, in groups of
      workers who performed similar rather than diverse tasks, and in North American
      workplaces compared with workplaces in Europe and Western Australia. These
      results could be used in the design of prospective sampling protocols and in
      future retrospective health-effects studies of workers in the nickel industries.

PMID- 10885882
TI  - Regulating the risk of tuberculosis transmission among health care workers.
AB  - The 1994 Centers for Disease Control and Prevention guidelines on preventing
      tuberculosis (TB) transmission among health care workers (HCWs), and the 1997
      Occupational Safety and Health Administration (OSHA) proposed TB standard, do not
      address the issue of acceptable risk. Further, many infection control personnel
      oppose OSHA's promulgating a standard because they believe most TB infections
      among HCWs are nonoccupational in origin. This article examines the relationship
      between TB infection and disease rates, and introduces a probability framework to
      apportion infection risk between occupational and nonoccupational exposure. It is
      argued that most TB infections among HCWs are work-related. A 0.2% overall annual
      risk of TB infection (accounting for both workplace and community exposure) is
      proposed as acceptable, because in the context of an infection surveillance
      program it limits an HCW's cumulative disease risk close to the value for the
      general United States population. Based on the probability framework, an estimate
      of the background community infection rate, and the traditional Wells-Riley risk
      model, it is shown that a target workplace infection risk value can be derived
      and expressed in terms of an expected pulmonary dose. The latter target dose
      informs risk management decision-making.

PMID- 10885883
TI  - Evaluation of odor and sensory irritation thresholds for methyl isobutyl ketone
      in humans.
AB  - Odor and irritation sensitivity for methyl isobutyl ketone (MIBK) was evaluated
      by obtaining olfactory detection thresholds and irritation (lateralization)
      thresholds, as well as perceived odor intensity and irritation ratings for three
      predetermined concentrations of MIBK, acetone, and phenylethyl alcohol.
      Subsequently, perceived annoyance ratings for the three concentrations were
      measured for 25 of the 40 volunteers. The mean odor detection threshold for MIBK
      was 10 ppm, and mean lateralization threshold was 8874 ppm. Calculating the fifth
      percentile for lateralization thresholds revealed that 95% of the sample
      population did not experience sensory irritation at or below 1802 ppm. Thus,
      while odor thresholds were well below the current recommended exposure limits (50
      ppm, threshold limit value; 75 ppm short-term exposure limit, American Conference
      of Governmental Industrial Hygienists), irritation thresholds were significantly
      higher. Odor and irritation intensity ratings for the chemicals increased with
      increasing concentrations and were higher for MIBK than for acetone. However,
      when the affective component of the irritation response (annoyance) was rated
      separately from the sensory component (perceived irritation), no significant
      differences were found between the irritancy of MIBK and acetone, suggesting that
      negative hedonic evaluations of MIBK (perhaps based on odor unfamiliarity)
      contributed to ratings of perceived irritation. These results validate coupling
      affective and sensory ratings to more effectively examine the human response to
      volatile stimuli. Results indicate that intranasal sensory irritation from MIBK
      will not be experienced at or near current exposure levels. Notably, the best
      predictors of perceived irritation to high concentrations of MIBK were those
      measures related to its odor, not to the threshold for sensory irritation,
      suggesting that negative responses to MIBK involve reactions to olfactory
      properties.

PMID- 10885884
TI  - Mechanistic understanding of aerosol emissions from a brazing operation.
AB  - Welding operations produce gaseous and aerosol by-products that can have adverse
      health effects. A laboratory furnace study was conducted to aid understanding of
      the chemical and aerosol behavior of a widely used, self-fluxing brazing alloy
      (89% Cu, 6% Ag, 5% P) that is also used with a supplemental fluxing compound to
      prevent oxidation at the molten metal surface. The results indicate that the
      aerosols generated by the alloy are transient (produced over a short duration of
      time) and are associated with mass transfer of phosphorus species from the molten
      metal surface to the surrounding gas. In contrast, when the alloy was used in
      conjunction with the supplemental fluxing compound, a relatively nontransient,
      submicron-size aerosol was generated that was several orders of magnitude higher
      in concentration. Thermodynamic equilibrium analysis suggests that fluoride (a
      major constituent in the fluxing compound) played a significant role in reacting
      with the brazing alloy metals to form gas phase metal fluoride compounds that had
      high vapor pressures when compared with their elemental or oxide forms. As these
      metal-fluoride vapors cooled, submicron-size particles were formed mainly through
      nucleation and condensation growth processes. In addition, the equilibrium
      results revealed the potential formation of severe pulmonary irritants (HF and
      BF3) from heating the supplemental fluxing compound. These results demonstrated
      the importance of fluxing compounds in the formation of brazing fumes, and
      suggest that fluxing compounds could be selected that serve their metallurgical
      intention and suppress the formation of aerosols.

PMID- 10885885
TI  - Limitations in application of Spearman's rank correlation to bioaerosol sampling
      data.
AB  - Bioaerosol sampling from various building sites, some of which were subjected to
      water damage and microbial growth, provided the opportunity to evaluate current
      recommendations for interpreting bioaerosol sampling data. Data from the ambient
      environment, a control building, and areas known to have microbial contamination
      were used as source data for random simulations. The simulations generated two
      comparison zones from microbial data from the same environment as a test model to
      identify the failure rate for Spearman's rank correlation. The results of the
      simulation indicated a failure rate approaching 60%, depending on the number of
      samples assigned to each zone by the simulation. The simulations indicated that
      nonparametric statistical treatment of bioaerosol data as currently recommended
      for building assessment purposes has limitations. An inordinately high Type II
      error (failure to reject a null hypothesis which is actually not true) is
      especially apparent when there are small numbers of samples. For example, in
      applying this methodology to clearance air sampling, a work zone subjected to
      removal of all moldy materials and a thorough particulate cleaning would still
      have a significant chance of failure solely due to the variability of the data,
      if individual samples are evaluated to identify "localized" contamination. This
      is significant with regard to the number of samples collected and the
      interpretation of individual samples in rendering evaluations of microbial
      contamination.

PMID- 10885886
TI  - Adjustment of occupational exposure limits for unusual work schedules.
AB  - A review of literature relating to the issue of adjustments of occupational
      exposure limits for unusual work shifts and unusual work schedules is described.
      The important issues relating to various adjustment models are discussed, and a
      number of conclusions are drawn. Tables of adjustment factors for 34 specific
      contaminants for 2 unusual schedules are given. A simple approach for use by
      industrial hygienists is proposed.

PMID- 10885887
TI  - The effects of adsorption on the reusability of Tedlar air sampling bags.
AB  - This study examined the adsorption and desorption behavior of six different
      organic compounds in Tedlar bags. Triplicate bags were filled with a gas mixture
      to yield concentrations of approximately 90 ppm of each analyte, then sampled and
      analyzed by capillary gas chromatography at predetermined intervals over a 3-week
      period. A first-order kinetic rate equation was fitted to the data, and measured
      rate coefficients for the six compounds ranged from zero for the nonadsorbing
      methyl tert-butyl ether to 0.09/day for the rapidly adsorbed methanol. Adsorptive
      losses of allyl alcohol, styrene, ethylbenzene, and propylene oxide were slower
      and less significant; rate coefficients ranged from 0.01 to 0.03/day. Following
      the adsorption phase of the study, the bags were put through a simple cleaning
      procedure consisting of N2-flushing and gentle heating steps. Analysis of
      variance was used to assess the effectiveness of each step. Five N2 flushes were
      adequate to remove residual methyl tert-butyl ether, allyl alcohol, and propylene
      oxide, but there seemed to be a degree of hysteresis for styrene and
      ethylbenzene. Combinations of flushing and heating also failed to remove all the
      styrene and ethylbenzene. Neither flushing nor heating removed any of the
      adsorbed methanol. Depending on the compound of concern, the reuse of Tedlar and
      other similar polyvinyl fluoride sample collection bags should be carefully
      considered before the start of any sampling program.

PMID- 10885888
TI  - Industrial responses to constrained OSHA regulation. Occupational Safety and
      Health Administration.
AB  - As part of the effort to reduce the size and economic impact of the federal
      establishment, congressional conservatives are proposing legislation to restrict
      the regulatory activity of the Occupational Safety and Health Administration
      (OSHA). These proposals push OSHA toward a purely consultative role, at a
      corresponding cost in direct regulatory capability. The Clinton administration's
      reinvention of government initiative is also moving OSHA toward a consultative
      role based on a strategy of cooperative compliance or industry self-regulation
      with a strong coercive foundation. Since both camps appear to agree that self
      regulation can assure a safe and healthy workplace, the remaining debate concerns
      the extent to which coercive regulation is still needed. National survey data on
      the industrial provision of occupational safety and health services in the
      manufacturing sector were used to measure changes in industrial safety and health
      activity between 1972-74 and 1981-83. In conjunction with data on OSHA command
      and-control regulatory activity from 1972 to 1979, these data permitted an
      examination of the relationship between command-and-control regulatory activities
      and changes in industrial behavior that could be regarded as a form of self
      regulation. This analysis showed that coercive regulation by OSHA in the 1970s
      was significantly related to industry self-regulation efforts, although the
      relationship varied by industrial facility employment size and type of regulatory
      coercion. These results indicate that coercive regulation should be retained as
      an industrial incentive in any self-regulation policy paradigm. The results also
      provide evidence that OSHA regulatory policy should be based on anticipated
      differences in industrial response to various coercive measures.

PMID- 10885889
TI  - How protective are respirator assigned protection factors: an uncertainty
      analysis.
AB  - This investigation evaluated the risk of overexposure for a selected assigned
      protection factor by performing Monte Carlo simulations. A model was constructed
      to assess respirator performance by calculating the concentration inside the
      respirator. Estimates of the factors that affect respirator performance were
      described as distributions. The distributions used a worst case estimate for
      concentration in the workplace, the worst case for respirator performance (the
      fifth percentile person), and the worst case for exhalation valve leakage. A
      Monte Carlo analysis then provided estimates of the percentage of time that
      concentration inside the respirator exceeded the occupational exposure limit
      (OEL). For a half-facepiece respirator with an APF of 10, the calculations
      indicated a low risk of being exposed above an OEL, with mean exposures being
      controlled well below an OEL.

PMID- 10885890
TI  - Stability of methylene chloride spiked passive samplers: an international
      shipping and transportation study.
AB  - A stability study was carried out by dynamically spiking Assay Technology Model
      541 passive samplers with known amounts of methylene chloride (MeCl2) and
      shipping them to facilities around the world. Once arrived, these samples
      remained on site briefly and then were returned to the laboratory in North
      Chicago, III. A total of 22 sets of samples was prepared. Each sample set
      contained four passive samplers: blank, low (2.5 ppm), medium (25 ppm), and high
      (125 ppm) concentrations. Twelve of the 22 sets were separated into 4 groups of 3
      sets, with each group defined as a cluster. One cluster was shipped to a
      pharmaceutical production facility in each country--South Africa, Pakistan, and
      Indonesia--and then shipped back to the lab, under normal shipping conditions.
      The fourth cluster was carried by one of the authors, who traveled through all
      three countries. The remaining 10 sets of samples were kept in the lab as
      controls. Each returning cluster was analyzed with two lab sets on arrival in the
      lab. Results obtained were evaluated using a t-test at a 95% confidence level. No
      significant differences were found in MeCl2 spiked passive samplers between
      traveled and lab controls, samples stored at room temperature and in the freezer,
      or analyzed right after being spiked and stored up to 7 weeks. It was concluded
      that MeCl2 spiked passive samplers were stable for at least 4 weeks at room
      temperature. There was no impact observed from international shipping and
      transportation on MeCl2 spiked passive samplers without temperature control.

PMID- 10885891
TI  - Performance characteristics of the button personal inhalable aerosol sampler.
AB  - The button inhalable aerosol sampler with a curved porous inlet recently was
      developed and evaluated as a stationary sampler in the laboratory and in the
      field. The present study focused on investigating its suitability for personal
      inhalable aerosol sampling. The button sampler was tested at two wind velocities
      (0.5 and 2.0 m/sec), three particle sizes (7, 29, and 70 microm) and three
      orientations to the wind (0, 90, and 180 degrees). The performance
      characteristics of the button sampler were compared with those of three other
      personal samplers--the IOM (Institute of Occupational Medicine), GSP, and 37-mm
      closed-face filter cassette. The experiments were conducted in a wind tunnel with
      the samplers mounted on a full-size manikin. The direction-specific sampling
      efficiency of the button sampler was found to be essentially independent of the
      wind direction and dependent on the wind velocity to a much smaller degree than
      that of the three other samplers. When direction-averaged, the fit of its
      sampling efficiency curve to the inhalability curve was found to be better than
      that of the 37-mm closed-face cassette, comparable with that of the GSP sampler,
      and less than that of the IOM sampler. The precision of the button sampler was
      found to be generally equal to or better than the precision of the comparison
      samplers. It was concluded that the button sampler can be successfully used as a
      personal inhalable aerosol sampler.

PMID- 10885892
TI  - Effect of temperature on the breakthrough of a charcoal tube during vinyl
      chloride monomer sampling.
AB  - This study evaluated the effects of temperature on breakthrough of two standard
      collection media at various concentrations during vinyl chloride monomer (VCM)
      sampling. The National Institute for Occupational Safety and Health (NIOSH) and
      Occupational Safety and Health Administration (OSHA) methods were evaluated. To
      determine whether breakthrough of VCM would occur at the extremes of exposure and
      temperature that might be encountered in some workplaces, air samples containing
      4 ppm (10.24 mg/m3), 8 ppm (20.45 mg/m3), 16 ppm (40.98 mg/m3), and 32 ppm (81.80
      mg/m3) of VCM were collected at temperatures of 4, 22, and 40 degrees C. Five
      liters of air was sampled at the rate of 0.05 L/min for 100 min using the
      activated charcoal tube recommended by NIOSH. A second tube was added to the
      sampling train to collect any VCM that might not have been absorbed in the first
      tube. To collect VCM air samples by the OSHA method, two carbon molecular sieve
      tubes were connected serially and 3 L of air was sampled at the rate of 0.05
      L/min for 60 min. A gas chromatograph with a flame ionization detector and ultra
      2 capillary column was used to analyze VCM. Significant breakthrough was found
      when sampling at higher temperatures with the NIOSH method. No breakthrough was
      found when samples were collected using the OSHA media at different temperatures
      and concentrations. Therefore, under hot ambient conditions (>22 degrees C), the
      possibility of breakthrough should be considered when sampling VCM by the NIOSH
      method.

PMID- 10885893
TI  - Determination of carbon monoxide with a modified zeolite sorbent and
      methanization-gas chromatography.
AB  - The purpose of this study was to develop an alternative sorbent sampling
      technique to concentrate CO from an air sample for subsequent instrumental
      analysis. Y52 zeolite doped with 9.4 wt % cuprous ions was found to have high
      capacity, stability to air, and thermal reversibility for CO. The Cu(I)-modified
      zeolite was packed in glass tubes, preceded by a drying tube containing silica
      gel. Air was sampled through the tubes at the flow rate of 100 mL/min. Collected
      CO was thermally desorbed at 300 degrees C and determined by gas chromatography
      with reduction of CO to methane and flame ionization detection (TD-GC-CH4-FID).
      Breakthrough capacity of the sorbent was found to be 2.74 mg CO per gram of
      sorbent. For 2-L air samples containing 12.5 to 100 ppm CO and 50% relative
      humidity at room temperature, recovery of CO was found to be 96.6% with pooled
      relative standard deviation of 5.8%. The estimated detection limit for a 2-L
      sample was 0.2 ppm. Collected CO was stable at room temperature for 1 day and up
      to 7 days at 4 degrees C if the sorbent tube was flushed with helium before
      storage. In field testing, the ratio of CO measured by the new technique and by a
      reference technique was found to be 0.93 with pooled relative standard deviation
      of 6.3%. This unique new sorbent coupled with TD-GC-CH4-FID shows promise as a
      sensitive and specific alternative for measurement of CO in air.

PMID- 10885894
TI  - Measuring performance of a half-mask respirator in a styrene environment.
AB  - A workplace protection factor (WPF) study was conducted with a half-mask air
      purifying respirator during fiber glass boat production. Styrene was the measured
      analyte, and the geometric mean WPF found was 39.7. Analytical detection limits,
      sample contamination, and pulmonary elimination from previous exposures or from
      skin absorption were identified as important considerations that can bias the
      WPFs measured. There were significant differences in the mean concentrations
      found inside the respirator when analyzed by time period. An increase in the
      concentration found inside the facepiece cavity and a decrease in the WPF over
      time was found for people with three or four measurements. This indicates either
      a change in performance of the respirator over time or a bias from low-level
      exposures during the day or skin absorption.

PMID- 10885895
TI  - Particle size characterizations of copper and zinc oxide exposures of employees
      working in a nonferrous foundry using cascade impactors.
AB  - This study characterized exposures to copper and zinc oxide as respirable or
      nonrespirable using personal impactors and compared the results with previous
      findings obtained using cyclones. Twenty-five sets of air samples were taken over
      a 10-month period using single jet cascade impactors. Five to six stages were
      used to capture and classify aerosols according to their aerodynamic diameter
      (d(ae)). These ranged from < 0.5 microm to > 10 microm d(ae). Twenty-two air
      samples were taken on employees casting brass alloys, and three samples were
      taken in areas in the vicinity where employees routinely worked. Twenty-one air
      samples were taken during the casting of a single brass alloy (containing 70%
      copper and 30% zinc), and the remaining samples were obtained from employees
      casting two different brass alloys: a nearly pure copper alloy and a nickel
      copper alloy. The results indicated that 55-96% (by mass) of all copper aerosols
      collected had a d(ae) > or = 10 microm. More than 85% (by mass) of all copper
      exposures were estimated as nonrespirable using the current ACGIH-CEN-ISO
      definition. Zinc oxide aerosols were collected at all stages of the impactors,
      with significant amounts found to have a d(ae) > or = 10 microm. More than 60%
      (by mass) of all zinc oxide exposures were estimated to be nonrespirable. A
      comparison of data collected using impactors and cyclones demonstrated that
      cyclones could be used to differentiate larger aerosol particles from fumes,
      rather than requiring the use of impactors. It is recommended that appropriate
      particle size selective sampling methods be used to classify exposures of metals
      to dusts and fumes.

PMID- 10885896
TI  - A study on the substitution of trichloroethylene as a spot remover in the textile
      industry.
AB  - Since the ban on 1,1,1-trichloroethane, the textile industry has been using
      trichloroethylene (TCE) as a spot remover to clean oil and grease stains from
      fabrics at inspection stations. TCE is a toxic substance recently classified as a
      probable human carcinogen. The purpose of this study was to use a systematic
      substitution procedure to replace TCE with a less hazardous option for spot
      removing in a textile company. After documenting the problem and understanding
      the processes involved, numerous sources of information were searched to identify
      the greatest number of plausible solutions. Then criteria were established to
      help consider only the options that seemed technically acceptable. Five options
      were retained: 1-bromopropane, a petroleum-based solvent, a
      hydrochlorofluorocarbon-based solvent, an appliance that uses hot steam, and the
      elimination of the oil and grease spots at the source. The latter option, which
      had been partially implemented by the textile company, was not considered in this
      study. After being tested in the workplace and evaluated on their technical
      plausibility and impact on health, safety, and environment, the remaining four
      options were not considered as suitable replacements for TCE. Thus, local
      ventilation with the implementation of further measures for the
      reduction/elimination of stains at the source were recommended to lower TCE
      exposure for workers.

PMID- 10885897
TI  - Effect of cyclosporin A on protein binding of teniposide in cancer patients.
AB  - We investigated the effect of cyclosporin A (CSA) on protein binding of
      teniposide (VM26) in 16 patients with metastatic renal cell carcinoma receiving
      i.v. VM26 alone over 24 h (total dose, 200 mg/m2) and in association with CSA (5
      mg/kg/2 h followed by 30 mg/kg/48 h i.v.). CSA was used in an attempt to overcome
      multidrug resistance. The unbound fraction (%fu) of VM26 was significantly
      (p=0.04) higher in the cycles with CSA (median 0.8; range 0.4-1.9) than in the
      cycles with VM26 alone (median 0.5; range 0.1-1.6). Both total VM26 area under
      curve concentration (AUC0-infinity) and free VM26 AUC0-infinity increased after
      treatment with CSA, but the median increase in free AUC0-infinity was higher (2.7
      fold) than total AUC0-infinity (1.5-fold) (p = 0.04). Bilirubin was significantly
      (p<0.01) increased after CSA but no association was observed between bilirubin
      level and %fu of VM26. Albumin was in the normal range after both VM26 alone and
      VM26 plus CSA. The nadir of absolute neutrophil count (ANC) after VM26 plus CSA
      (median 700/microl, range <100-2860/microl) was lower than after VM26 alone
      (median 1900/microl, range 200-6000/microl) (p = 0.0007). The median percentage
      of ANC compared to the pretreatment value (ANC nadir/ANC pretreatment x 100) was
      39.0% (range 3.1-98.8%) in the cycles with VM26 alone and 16.9% (range 1.4-97.9%)
      (p = 0.007) after VM26 plus CSA. Percentage change of neutrophils significantly
      correlated with free AUC0-infinity VM26 in the cycles with VM26 alone and VM26
      plus CSA (p = 0.04, r = -0.53 and p = 0.04, r = -0.52, respectively). Only a
      trend which failed to reach significance was observed between total AUC0-infinity
      VM26 and percentage change of neutrophils in the cycles with VM26 alone and in
      association with CSA (p = NS, r = -0.33 and p = 0.055, r = -0.49, respectively).
      In conclusion, patients treated with CSA had higher systemic exposure to unbound
      VM26.

PMID- 10885899
TI  - Prolonged infusion of gemcitabine in stage IV breast cancer: a phase I study.
AB  - Gemcitabine is an effective agent in the treatment of metastatic breast cancer.
      The phosphorylation of gemcitabine into the active gemcitabine triphosphate
      (dFdCTP) is catalyzed by deoxycytidine kinase. This enzyme is saturated at plasma
      concentrations achieved after an infusion over 30 min. Therefore accumulation of
      higher intracellular dFdCTP concentrations, which may result in an enhanced
      antineoplastic activity, cannot be achieved by higher dosage, but only by
      prolonged infusion time. The objectives of this phase I trial were to determine
      the dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD) of
      gemcitabine given as a 6 h i.v. infusion. Patients with metastatic breast cancer
      were treated with gemcitabine as a 6 h infusion on days 1, 8 and 15 every 4
      weeks. The starting dose was 200 mg/m2 with an interindividual escalation in 50
      mg/m2 increments. Sixteen patients received 196 doses through three dose levels.
      All patients were assessable for toxicity, 13 assessable for response. The MTD
      was 250 mg/m2. DLT was observed at 300 mg/m2 consisting of a reversible elevation
      of transaminases WHO grade 3 in two patients and cutaneous toxicity grade 3 in
      one patient. Most common non-hematologic toxicities were mild to moderate and
      rapidly reversible elevation of liver enzymes in all patients, nausea and
      vomiting (four patients grade 2, five patients grade 3), and mild alopecia.
      Hematologic toxicity was mild with neutropenia WHO grade 3 and 4 in only one
      patient each, and no grade 3 thrombocytopenia. One patient achieved a complete
      remission and another patient a partial response, for an overall response rate of
      15% (two of 13). In addition, seven patients (54%) had stable disease and four
      (31%) failed to respond to the treatment. We conclude gemcitabine 250 mg/m2 days
      1, 8 and 15 every 4 weeks can be safely administered as 6 h infusion. Toxicity,
      especially myelosuppression, is surprisingly mild. Based on this result a phase
      II study with 250 mg/m2 administered over 6 h was initiated to determine the
      efficacy.

PMID- 10885898
TI  - Phase II trial of 5-fluorouracil, folinic acid and recombinant alpha-2a
      interferon in patients with advanced colorectal cancer.
AB  - A clinical trial regimen modulating 5-fluorouracil (5-FU) with both folinic acid
      (FA) and recombinant alpha-2a-interferon (ralpha-2a-IFN) was noted to have a
      response rate of 54% and median survival of 16.3 months (Grem et al., J Clin
      Oncol 1993, 11: 1737-45). Reported herein is a phase II trial performed to
      further examine this regimen in metastatic colorectal cancer. Fifty-one patients
      with histologically proven, measurable advanced colorectal cancer with no prior
      therapy for metastatic disease were enrolled. ralpha-2a-IFN, 5 MIU/m2/day was
      given s.c. on days 1-7. FA, 500 mg/m2/day, and 5-FU, 370 mg/m2/day, were given
      i.v. on days 2-6. Cycles were repeated at 3 week intervals. Three complete and 12
      partial responses were observed for an overall response rate of 29% (95%
      confidence interval: 18-45%). The median time to treatment failure and median
      survival were 4.6 and 15.5 months, respectively. Dose-limiting toxicities
      encountered were gastrointestinal, and included diarrhea, stomatitis, nausea and
      vomiting. These results do not support the concept of using concurrent ralpha-2a
      IFN and FA as biochemical modulators of 5-FU. We observed increased toxicity and
      similar efficacy compared to using either modulator separately with 5-FU.

PMID- 10885900
TI  - Severe hemolytic uremic syndrome in an advanced ovarian cancer patient treated
      with carboplatin and gemcitabine.
AB  - Hemolytic uremic syndrome (HUS) is a rare clinical and biological entity. HUS has
      been reported after several anticancer chemotherapies and most often after
      mitomycin C-based chemotherapy regimens. Little information is available
      concerning the occurrence and outcome of this syndrome after administration of
      more recent chemotherapeutic agents. We present a case of HUS in an advanced
      ovarian cancer patient treated with carboplatin and gemcitabine, and described
      its favorable outcome after chemotherapy interruption and supportive care with a
      1 year follow-up.

PMID- 10885901
TI  - Vinflunine, a new vinca alkaloid: cytotoxicity, cellular accumulation and action
      on the interphasic and mitotic microtubule cytoskeleton of PtK2 cells.
AB  - Vinflunine, a newly synthesized derivative, possesses marked in vivo antitumor
      properties and, like other alkaloids, inhibits in vitro tubulin assembly at
      microM concentrations. However, in contrast to other vinca alkaloids, vinflunine
      exhibits relatively low in vitro cytotoxic potency. The aim of this report was to
      investigate whether the action(s) of vinflunine on the microtubule cytoskeleton
      could account for its cytotoxicity or if its cellular action requires another
      molecular target. Four vinca alkaloids used in cancer therapy and vinflunine were
      studied using PtK2 cells. Their activities on the most dynamic microtubules were
      investigated in mitosis and in interphase by evaluating the disturbance of the
      metaphase plate and the splitting of the diplosome, respectively. No correlation
      was observed between the cellular accumulation of these compounds and either
      their cytotoxicity or their action(s) on the microtubule cytoskeleton. In
      contrast, cytotoxicity, mitotic disturbance and diplosome splitting were observed
      in the nM range for vinblastine, vincristine, vindesine and vinorelbine, although
      these events occurred at 10 times higher concentrations in the case of
      vinflunine. Hence, dynamic modifications of both the mitotic and interphasic
      microtubule cytoskeleton are compatible with in vitro cytotoxicity of vinflunine,
      raising questions about the conventional biochemical screening of these vinca
      alkaloids.

PMID- 10885902
TI  - Preferential repair of the N-ras gene in K 562 cells after exposure to cisplatin.
AB  - Cisplatin is one of the most active and widely used anticancer drugs; however,
      its clinical efficiacy is often limited by the development of resistance. Since
      several studies indicated that ras oncogenes may modulate the cellular response
      to cisplatin or radiation, we investigated the gene-specific repair of the N-ras
      gene in the human K 562 cell line after exposure to cisplatin using a novel
      nonradioactive polymerase chain reaction inhibition assay. This assay is based on
      the fact that DNA lesions can block the Taq polymerase and thereby result in a
      decreased amplification of a damaged segment compared to the amplification of the
      same segment in a non-damaged template. The overall genomic repair rate was
      measured by atomic absorption spectroscopy. Immediately after cisplatin exposure
      no amplification segment was observed. However, a complete restoration of the N
      ras gene (2.4 kb) was seen after 8 h posttreatment incubation. In contrast, only
      60% of the overall genome was repaired at this time. Our results clearly indicate
      that cisplatin-induced DNA lesions are more efficiently removed from transcribed
      regions within the DNA, suggesting that the efficiency of DNA repair in a given
      gene may be correlated to its transcriptional activity. Since ras oncogenes
      control several cellular signal transduction pathways, known to be involved in
      DNA damage response, preferential repair of the N-ras gene could therefore be an
      important step to prevent inactivation of cellular defense mechanisms after
      exposure to genotoxic agents.

PMID- 10885903
TI  - Differential in vitro interactions of a series of clinically useful topoisomerase
      interacting compounds with the cleavage/religation activity of the human
      topoisomerase IIalpha and IIbeta isoforms.
AB  - The topoisomerase II (TOP2)-associated DNA cleavage activity and the DNA sequence
      preference of 20 antitumor drugs, including 15 TOP2-interacting compounds, have
      been defined. Four major classes of drugs have been identified: (i) those which
      enhanced the stabilization of cleavable complexes at a single major site (e.g.
      amsacrine, doxorubicin), or (ii) at many sites (e.g. etoposide, azatoxin), with
      chemically related compounds having very similar, although not identical,
      cleavage patterns (e.g. etoposide, GL331 and Top-53); (iii) those which inhibited
      DNA breakage (e.g. aclarubicin, actinomycin D); and (iv) those which did not
      visibly interfere with TOP2-mediated cleavable complexes (e.g. ICRF-187,
      camptothecin). All drugs tested induced similar overall patterns of sites of
      preferred DNA cleavage, in the presence either of the two known isoforms,
      TOP2alpha or TOP2beta, although relative intensities of signals at each position
      varied. It has been further shown that etoposide and its derivatives blocked the
      religation step downstream of the DNA cleavage step, whereas amsacrine,
      ellipticine, azatoxin and genistein acted upstream through enhancement of DNA
      cleavage. The information provided by this mechanistically based comparison can
      now be exploited in designing or synthesizing novel TOP2-interacting agents.

PMID- 10885904
TI  - Modulation of 5-fluorouracil by 5-ethyl-2'-deoxyuridine on cell lines expressing
      different dihydropyrimidine dehydrogenase activities.
AB  - The purpose of the present study was to clarify the significance of the
      inhibition of dihydropyrimidine dehydrogenase (DPD) in the modulation of 5
      fluorouracil (5-FU) action by 5-ethyl-2'-deoxyuridine (EUdR). Four human cell
      lines, which differed in their susceptibility to 5-FU and in their DPD activity,
      were selected as biological objects. Several other enzymes of pyrimidine
      metabolism, i.e. thymidylate synthase (TS), thymidine kinase (TK) and pyrimidine
      nucleoside phosphorylase (PNP), which might be involved in the 5-FU action were
      also studied to elucidate their potential role in the modulation of 5-FU
      cytotoxicity. Two out of the four cell lines, i.e. COLO1 and SW620, showed low
      (57 and 28 pmol/min/mg protein) and the other two cell lines, i.e. CAL51 and
      CAL33, showed high (235 and 184 pmol/min/mg protein) DPD activity, respectively.
      In our study, contrary to our expectation, no correlation between the DPD and TS
      activity of the cell lines and their 5-FU sensitivity could be observed. EUdR
      alone was cytotoxic only on CAL33 cells in a concentration below 1 mM (IC50=194
      microM) which might be due to the high TK activity (857 pmol/min/mg protein)
      measured in this cell line, favoring the formation of the phosphorylated
      nucleotides EdUMP and EdUTP indispensable for the inhibition of TS and DNA
      polymerase, respectively. Surprisingly, although EUdR by metabolizing to EUra was
      able to reduce the high activity of DPD in CAL33 and CAL51 cells by 47 and 55%,
      respectively, no potentiation of the 5-FU action occurred on these cell lines. On
      the contrary, enhancement of the 5-FU cytotoxicity was demonstrated on COLO1 and
      SW620 cells with low DPD activity. Our findings suggest that the 5-FU modulatory
      action of EUdR may be directed on other molecular targets than DPD as well, i.e.
      the augmentation of TS inhibition by EdUMP as demonstrated on SW620 cells might
      be one of these mechanisms.

PMID- 10885905
TI  - Apoptosis induction and cell cycle perturbation in human hepatoma hep G2 cells by
      10-hydroxycamptothecin.
AB  - 10-Hydroxycamptothecin (HCPT), a DNA topoisomerase I inhibitor, is an antitumor
      alkaloid isolated from a Chinese tree, Camptotheca acuminata, and exhibits a
      remarkable antihepatoma effect. We studied HCPT to determine whether or not its
      anti-hepatoma activity occurs through apoptosis induction and cell cycle
      disturbance using the MTT method, DAPI staining, agarose gel electrophoresis and
      flow cytometric analysis. The results showed that HCPT inhibited proliferation of
      human hepatoma Hep G2, Bel-7402 and Bel-7404 cells at an optimal concentration of
      0.1 microg/ml. This growth inhibition was dose and time dependent, and was
      accompanied by evidence of apoptotic changes and cell cycle perturbation in Hep
      G2 cells. Chromatin condensation and nuclear fragmentation were observed in Hep
      G2 cells by fluorescence microscopy. Agarose gel electrophoresis showed
      internucleosomal DNA fragmentation ('ladder pattern') of Hep G2 cells following
      treatment with HCPT, in a concentration- and time-dependent manner. Flow
      cytometry showed that HCPT induced a massive hypodiploid cell population and
      arrested cells in G2/M phase (at low dose) or in S phase (at high dose) in Hep G2
      cells. The results of this study suggest that the anti-hepatoma effect of HCPT
      may result from apoptosis induction and cell cycle disturbance.

PMID- 10885906
TI  - Synthesis and cytotoxic activity of thiazolyl indolequinones.
AB  - A number of thiazolyl indolequinones have been prepared and evaluated for their
      antitumor properties. The compounds were synthesized from the appropriate indole,
      building up the thiazole ring using the Hantzsch reaction. Cytotoxic activity was
      determined in the human breast cancer SKBr3 cell line. Selected compounds were
      also studied in human lung carcinoma A549 and PV9 cell lines. In addition, some
      compounds were evaluated for their possible bioreductive action by determining
      their cytotoxicity towards V79 Chinese hamster lung fibroblasts in air and under
      anaerobic (hypoxic) conditions.

PMID- 10885907
TI  - Synthesis and anticancer activities of 4-oxobenzopyrano[2,3-d]pyrimidines.
AB  - Several 2-aryl-4-oxoxbenzopyrano[2,3-d]pyrimidines have previously been shown to
      exhibit in vivo antitumor activity in mice with P388 lymphocytic leukemia. In the
      present study, a series of novel substituted benzopyrano[2,3-d]pyrimidines have
      been prepared and tested for cytotoxic activity against a panel of cancer cell
      lines including the P388 lymphocytic leukemia cell line. The unsubstituted parent
      compound, some methoxylated derivatives and a cyclohexyl derivative all exhibited
      potent cytotoxic activity (IC50 values 0.3-0.64 microM). A number of derivatives,
      including the unsubstituted parent pyrimidine, were shown to cause a significant
      perturbation in cell cycle kinetics with an observed 2- to 3-fold increase in
      cells in the G2/M phase of the cell cycle. Furthermore, a polymethoxylated
      derivative, 2-(3,4,5-trimethoxyphenyl)-9-methoxy-4-oxo-2,3-dihydrobenzopyrano[
      2,3-d]pyrimidine 13, was shown to be selectively active against a number of human
      ovarian cell lines.

PMID- 10885908
TI  - Time-schedule dependency of S 16020, a new topoisomerase II inhibitor.
AB  - S 16020 is a new olivacine derivative which has been shown to intercalate into
      DNA and to stabilize the cleavable complex formed by DNA and purified
      topoisomerase II. The aim of the present study was to estimate the impact of time
      exposure on the in vitro activity of S 16020. This was done on seven cancer cell
      lines of human origin (head and neck, kidney, and ovary). Doxorubicin was used as
      a reference drug. The cytotoxic activity of S 16020 remained stable during at
      least 3 h. A loss of activity of about 30% was apparent after 6 or 24 h
      preincubation. This relative loss of activity reached about 50% after 72 h
      preincubation. Considering all tested cell lines, the average IC50 decrease was
      89+/-8% for S 16020 with incubation times between 1 and 72 h. An exposure index
      (El) was calculated to evaluate the effect of time on the cytotoxic efficacy. The
      reference time was 1 h exposure. The El values were corrected to take into
      account the loss of drug activity. For the majority of cell lines EI values were
      greater than 1 for both drugs, particularly after a 6 h exposure time. This means
      that, in this case as compared to the shorter exposure (1 h), increasing time has
      a relative detrimental effect on drug efficacy. For the two cancer cell lines of
      ovarian origin, El values remained close to 1 for both drugs whatever the total
      exposure time. This means that, in this case, time and concentration have
      symmetrical effects on cell survival. The pharmacological information provided by
      the present study may be useful in designing future clinical trials on this
      potentially interesting new topoisomerase II inhibitor. As a consequence of these
      data, 1 and 3 h drug administration schedules are currently tested during phase I
      trials.

PMID- 10885909
TI  - The cost-effectiveness of paclitaxel (Taxol) + cisplatin is similar to that of
      teniposide + cisplatin in advanced non-small cell lung cancer: a multicountry
      analysis.
AB  - A large randomized clinical trial in advanced, previously untreated, non-small
      cell lung cancer (NSCLC) patients revealed better response rates and better
      tolerance for paclitaxel+cisplatin (TAXCIS) compared to teniposide+cisplatin
      (TENCIS). Since economic evidence is receiving increasing attention in health
      care, we conducted an economic evaluation based on the trial results in The
      Netherlands, Belgium, France and Spain. The evaluation was based on (i)
      differences in drug costs, (ii) differences in chemotherapy administration and
      (iii) the economic consequences of significantly different clinical outcomes in
      the trial: anemia, thrombocytopenia, neutropenia, neuropathy and
      arthralgia/myalgia. Data regarding medical resource utilization were obtained
      from clinician interviews using a Delphi technique and validated by patient
      charts analysis. Differences in medical management occurred across countries, but
      TAXCIS was cost-additive in all countries, i.e. the extra cost of chemotherapy
      was only partially compensated by savings in medical resource use, resulting in a
      net cost per patient of US$2311. In the trial, TAXCIS therapy produced a 37%
      response rate compared to 26% for TENCIS. The cost per extra responder for TAXCIS
      is on average US$21011, which is comparable to the cost per responder obtained
      with TENCIS (US$27266). Thus, the cost-effectiveness of TAXCIS, expressed in cost
      per responder, is similar to the cost-effectiveness obtained with TENCIS.

PMID- 10885910
TI  - Medical care consumption in a phase III trial comparing irinotecan with
      infusional 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer
      after 5-FU failure.
AB  - We evaluated economic implications of treatment with irinotecan, following a RCT
      which demonstrated significantly increased survival at 1 year with irinotecan
      (45%) compared to infusional 5-fluorouracil (5-FU) (32%) in patients with
      metastatic colorectal cancer. Medical care consumption data were collected
      prospectively alongside the trial, with 256 patients followed for a median of 10
      months. Follow-up was prolonged beyond treatment failure and medical care
      consumption was not protocol driven, enabling a realistic evaluation of economic
      implications. Medical care consumption associated with chemotherapy
      administration was lower with irinotecan as compared with infusional 5-FU. The
      cumulative number of days in hospital due to treatment toxicity and cancer
      complications, which is the key cost driver, was 14.4 (95% CI: 10.7-18.1) with
      irinotecan versus 17.5 (95% CI: 11.7-23.3) with infusional 5-FU. Thus, the
      survival benefit with second-line irinotecan compared to infusional 5-FU in
      patients with advanced colorectal cancer was achieved without increasing medical
      care consumption.

PMID- 10885911
TI  - Politics surrounding last winter's flu crisis. NHS's fundamental problems must be
      solved.

PMID- 10885912
TI  - Politics surrounding last winter's flu crisis. Spin doctoring the problem.

PMID- 10885913
TI  - Politics surrounding last winter's flu crisis. Elderly people deserve more than a
      free television licence.

PMID- 10885914
TI  - Cerebral dysfunction after water pollution incident in Camelford. Results were
      biased by self selection of cases.

PMID- 10885915
TI  - Cerebral dysfunction after water pollution incident in Camelford. Study has
      several methodological errors.

PMID- 10885916
TI  - Cerebral dysfunction after water pollution incident in Camelford. Inappropriate
      study, inappropriate conclusions.

PMID- 10885917
TI  - Cerebral dysfunction after water pollution incident in Camelford. Study may
      prolong the agony.

PMID- 10885918
TI  - Inadvertent dural puncture. Avoiding unintentional puncture is a primary goal of
      obstetric anaesthetists.

PMID- 10885919
TI  - Inadvertent dural puncture. Further study is needed of possible long term
      sequelae.

PMID- 10885920
TI  - Registering clinical trials. Register of clinical trials in children must be set
      up.

PMID- 10885921
TI  - Global medical knowledge database is proposed.

PMID- 10885922
TI  - Registering clinical trials. Italian clinical trial registry is kept by
      pharmacists on local ethical committees.

PMID- 10885923
TI  - Problem solving treatment for depression. Does the paper really prove that
      problem solving treatment is helpful?

PMID- 10885924
TI  - Problem solving treatment for depression. Cost effectiveness is not clear.

PMID- 10885925
TI  - Problem solving treatment for depression. Study should have included placebo
      group.

PMID- 10885926
TI  - The debate over complementary medicine continues. Evidence for homoeopathy is
      lacking.

PMID- 10885927
TI  - The debate over complementary medicine continues. "Complementogenic" disease may
      be increasing.

PMID- 10885928
TI  - The debate over complementary medicine continues. Debate of the 1840s is revised.

PMID- 10885929
TI  - More radiotherapy resources are needed for children as well as adults.

PMID- 10885931
TI  - Twists in the tale of impossible means. The editor invites everyone to dinner.

PMID- 10885930
TI  - Twists in the tale of impossible means. In which a copy of the original
      manuscript is found safe in Norway.

PMID- 10885932
TI  - Twists in the tale of impossible means. The researchers rejoice that the gremlins
      were at the BMJ after all.

PMID- 10885933
TI  - Twists in the tale of impossible means. The reviewer shows that the gremlins
      might have attacked on several fronts.

PMID- 10885934
TI  - Embryology of the circulation.

PMID- 10885935
TI  - Absence of written guidelines in neonatal units for ECMO referral may delay
      referral.

PMID- 10885936
TI  - Infant mortality rate in Sheffield.

PMID- 10885937
TI  - Evaluating urinary flow and solute excretion from urinary creatinine in the first
      week of life.

PMID- 10885938
TI  - Use of inhaled nitric oxide to improve oxygenation in the neonate.

PMID- 10885939
TI  - Rationing in child health services.

PMID- 10885940
TI  - Missed opportunities for preventing perinatal hepatitis B infection.

PMID- 10885941
TI  - Submitral pseudoaneurysm in purulent pericarditis.

PMID- 10885942
TI  - Cost effectiveness of statins.

PMID- 10885943
TI  - Technician run open access exercise electrocardiography.

PMID- 10885944
TI  - Infotech pharma 2000.

PMID- 10885946
TI  - Surgical treatment of pancreatic cancer. Patient Care Committee of the Society
      for Surgery of the Alimentary Tract (SSAT).

PMID- 10885945
TI  - Immunologic tolerance to organ transplants.

PMID- 10885947
TI  - Surgical treatment of cancer of the colon or rectum. Patient Care Committee of
      the Society for Surgery of the Alimentary Tract (SSAT).

PMID- 10885948
TI  - Surgical treatment of diverticulitis. Patient Care Committee of the Society for
      Surgery of the Alimentary Tract (SSAT).

PMID- 10885949
TI  - Surgical management of hemorrhoids. Patient Care Committee of the Society for
      Surgery of the Alimentary Tract (SSAT).

PMID- 10885950
TI  - Surgical repair of groin hernias. Patient Care Committee of the Society for
      Surgery of the Alimentary Tract (SSAT).

PMID- 10885951
TI  - Splenectomy. Patient Care Committee of the Society for Surgery of the Alimentary
      Tract (SSAT).

PMID- 10885953
TI  - Management of Barrett's esophagus. The Society for Surgery of the Alimentary
      Tract (SSAT), American Gastroenterological Association (AGA), American Society
      for Gastrointestinal Endoscopy (ASGE) Consensus Panel.

PMID- 10885952
TI  - Management of colonic polyps and adenomas. Patient Care Committee of the Society
      for Surgery of the Alimentary Tract (SSAT).

PMID- 10885954
TI  - Pathology of Barrett's esophagus.

PMID- 10885956
TI  - Reversal of Barrett's esophagus with electrocoagulation and laser.

PMID- 10885955
TI  - Medical treatment of Barrett's esophagus.

PMID- 10885957
TI  - Antireflux surgery in the management of Barrett's esophagus.

PMID- 10885958
TI  - Photodynamic therapy in the management of Barrett's esophagus with dysplasia.

PMID- 10885959
TI  - High-grade dysplasia in Barrett's esophagus: surveillance or operation?

PMID- 10885960
TI  - Laparoscopic fundoplication for dysphagia and peptic esophageal stricture.

PMID- 10885961
TI  - Interval appendectomy in the laparoscopic era.

PMID- 10885962
TI  - Preoperative biliary drainage: impact on intraoperative bile cultures and
      infectious morbidity and mortality after pancreaticoduodenectomy.

PMID- 10885963
TI  - Physiology and metabolism. Web alert.

PMID- 10885964
TI  - Symposium on brachial plexus surgery. A Narakas Club. Barcelona (Spain)--13 and
      14 March 1999.

PMID- 10885965
TI  - Ninth annual meeting of the American Society for Peripheral Nerve. June 19-21,
      1999--Los Angeles, CA.

PMID- 10885966
TI  - [Auditory screening of newborn and young infants].

PMID- 10885967
TI  - [Hematology].

PMID- 10885968
TI  - Is 200mg lamotrigine daily analgesic or not?

PMID- 10885970
TI  - Updated data for chart in NSCLC: a missed opportunity.

PMID- 10885971
TI  - Tracheal aminophylline administration. An alternative route of administration
      during cardiopulmonary resuscitation?

PMID- 10885972
TI  - Trigonometric method of computing the coordinates of invisible targets in
      functional neurosurgery.

PMID- 10885973
TI  - Phosphodiesterases: the journey towards therapeutics.

PMID- 10885974
TI  - The many faces of binding artefacts.

PMID- 10885975
TI  - Beta-blocker eyedrops and nocturnal arterial hypotension.

PMID- 10885976
TI  - A "missed" cryoglobulin: the importance of in vitro calcium concentration.

PMID- 10885977
TI  - Computed digital absorptiometry of the hand: screening method of bone loss in
      postmenopausal women in RA.

PMID- 10885978
TI  - Rubella infection in adult onset Still's disease.

PMID- 10885979
TI  - Raised plasma adrenomedullin patients with systemic sclerosis complicated by
      pulmonary hypertension.

PMID- 10885980
TI  - Avascular necrosis of a single vertebral body, an atypical site of disease in a
      secondary APLS.

PMID- 10885981
TI  - Immunoglobulin and lymphocyte decrease concurrent with adverse reactions induced
      by methotrexate for RA.

PMID- 10885982
TI  - Respiratory syncytial virus infection in adults.
AB  - Respiratory syncytial virus (RSV) is now recognized as a significant problem in
      certain adult populations. These include the elderly, persons with
      cardiopulmonary diseases, and immunocompromised hosts. Epidemiological evidence
      indicates that the impact of RSV in older adults may be similar to that of
      nonpandemic influenza. In addition, RSV has been found to cause 2 to 5% of adult
      community-acquired pneumonias. Attack rates in nursing homes are approximately 5
      to 10% per year, with significant rates of pneumonia (10 to 20%) and death (2 to
      5%). Clinical features may be difficult to distinguish from those of influenza
      but include nasal congestion, cough, wheezing, and low-grade fever. Bone marrow
      transplant patients prior to marrow engraftment are at highest risk for pneumonia
      and death. Diagnosis of RSV infection in adults is difficult because viral
      culture and antigen detection are insensitive, presumably due to low viral titers
      in nasal secretions, but early bronchoscopy is valuable in immunosuppressed
      patients. Treatment of RSV in the elderly is largely supportive, whereas early
      therapy with ribavirin and intravenous gamma globulin is associated with improved
      survival in immunocompromised persons. An effective RSV vaccine has not yet been
      developed, and thus prevention of RSV infection is limited to standard infection
      control practices such as hand washing and the use of gowns and gloves.

PMID- 10885984
TI  - Applications of differential-display reverse transcription-PCR to molecular
      pathogenesis and medical mycology.
AB  - The host-fungus interaction is characterized by changes in gene expression in
      both host and pathogen. Differential-display reverse transcription PCR (DDRT-PCR)
      is a PCR-based method that allows extensive analysis of gene expression among
      several cell populations. Several limitations and drawbacks to this procedure
      have now been addressed, including the large number of false-positive results and
      the difficulty in confirming differential expression. Modifications that simplify
      the reaction time, allow the use of minute quantities of RNA, or address unusual
      species- or gene-specific sequences have been reported. DDRT-PCR has been used to
      address biological questions in mammalian systems, including cell
      differentiation, cell activation, cell stress, and identification of drug
      targets. In microbial pathogenesis and plant pathogenesis, DDRT-PCR has allowed
      the identification of virulence factors, genes involved in cell death, and
      signaling genes. In Candida albicans, DDRT-PCR studies identified TIF-2, which
      may play a role in the upregulation of phospholipases, and the stress-related
      genes, CIP1 and CIP2. In Histoplasma capsulatum and C. albicans, genes involved
      in the host-pathogen interaction, including a member of the 100-kDa family in
      Histoplasma and an ALS and 14-3-3 gene in Candida, were potentially identified by
      DDRT-PCR. Although very few reports have been published in medical mycology,
      studies in mammalian, nonfungal microbial, and plant pathogen systems are easily
      applied to basic questions in fungal pathogenesis and antifungal therapeutics.

PMID- 10885983
TI  - Risk and management of blood-borne infections in health care workers.
AB  - Exposure to blood-borne pathogens poses a serious risk to health care workers
      (HCWs). We review the risk and management of human immunodeficiency virus (HIV),
      hepatitis B virus (HBV), and hepatitis C virus (HCV) infections in HCWs and also
      discuss current methods for preventing exposures and recommendations for
      postexposure prophylaxis. In the health care setting, blood-borne pathogen
      transmission occurs predominantly by percutaneous or mucosal exposure of workers
      to the blood or body fluids of infected patients. Prospective studies of HCWs
      have estimated that the average risk for HIV transmission after a percutaneous
      exposure is approximately 0.3%, the risk of HBV transmission is 6 to 30%, and the
      risk of HCV transmission is approximately 1.8%. To minimize the risk of blood
      borne pathogen transmission from HCWs to patients, all HCWs should adhere to
      standard precautions, including the appropriate use of hand washing, protective
      barriers, and care in the use and disposal of needles and other sharp
      instruments. Employers should have in place a system that includes written
      protocols for prompt reporting, evaluation, counseling, treatment, and follow-up
      of occupational exposures that may place a worker at risk of blood-borne pathogen
      infection. A sustained commitment to the occupational health of all HCWs will
      ensure maximum protection for HCWs and patients and the availability of optimal
      medical care for all who need it.

PMID- 10885985
TI  - Bartonella infection in animals: carriership, reservoir potential, pathogenicity,
      and zoonotic potential for human infection.
AB  - Recent observations have begun to support a role for Bartonella spp. as animal as
      well as human pathogens. Bartonella spp. are vector-transmitted, blood-borne,
      intracellular, gram-negative bacteria that can induce prolonged infection in the
      host. Persistent infections in domestic and wild animals result in a substantial
      reservoir of Bartonella organisms in nature that can serve as a source for
      inadvertent human infection. The prevalence of bacteremia can range from 50 to
      95% in selected rodent, cat, deer, and cattle populations. Dogs infected with
      Bartonella spp. can develop lameness, endocarditis, granulomatous lymphadenitis,
      and peliosis hepatis, lesions that have also been reported in association with
      human infection. Understanding the role of Bartonella spp. as pathogens in cats
      and other wild or domestic animals awaits the results of additional studies.
      Considering the extensive animal reservoirs and the large number of insects that
      have been implicated in the transmission of Bartonella spp., both animal and
      human exposure to these organisms may be more substantial than is currently
      believed.

PMID- 10885986
TI  - Molecular aspects of severe malaria.
AB  - Human infections with Plasmodium falciparum may result in severe forms of
      malaria. The widespread and rapid development of drug resistance in P. falciparum
      and the resistance of the disease-transmitting mosquitoes to insecticides make it
      urgent to understand the molecular background of the pathogenesis of malaria to
      enable the development of novel approaches to combat the disease. This review
      focuses on the molecular mechanisms of severe malaria caused by the P. falciparum
      parasite. The nature of severe malaria and the deleterious effects of parasite
      derived toxins and host-induced cytokines are introduced. Sequestration, brought
      about by cytoadherence and rosetting, is linked to severe malaria and is mediated
      by multiple receptors on the endothelium and red blood cells. P. falciparum
      erythrocyte membrane protein 1 (PfEMP1) is the ligand responsible for a majority
      of binding interactions, and the multiply adhesive features of this sticky
      molecule are presented. Antigenic variation is also a major feature of PfEMP1 and
      of the surface of the P. falciparum-infected erythrocyte. Possible mechanisms of
      P. falciparum antigenic variation in asexual stages are further discussed. We
      conclude this review with a perspective and suggestions of important aspects for
      future investigations.

PMID- 10885989
TI  - Automated beta galactosidase activity bioassay for adult Daphnia magna versus
      classic immobilization test.

PMID- 10885990
TI  - Acute toxicity of inorganic chloramines to Daphnia magna in two types of dilution
      water.

PMID- 10885991
TI  - Use of recultivated electrofilter ash dumping areas for sheep breeding.

PMID- 10885987
TI  - Babesiosis.
AB  - Babesiosis is an emerging, tick-transmitted, zoonotic disease caused by
      hematotropic parasites of the genus Babesia. Babesial parasites (and those of the
      closely related genus Theileria) are some of the most ubiquitous and widespread
      blood parasites in the world, second only to the trypanosomes, and consequently
      have considerable worldwide economic, medical, and veterinary impact. The
      parasites are intraerythrocytic and are commonly called piroplasms due to the
      pear-shaped forms found within infected red blood cells. The piroplasms are
      transmitted by ixodid ticks and are capable of infecting a wide variety of
      vertebrate hosts which are competent in maintaining the transmission cycle.
      Studies involving animal hosts other than humans have contributed significantly
      to our understanding of the disease process, including possible pathogenic
      mechanisms of the parasite and immunological responses of the host. To date,
      there are several species of Babesia that can infect humans, Babesia microti
      being the most prevalent. Infections with Babesia species generally follow
      regional distributions; cases in the United States are caused primarily by B.
      microti, whereas cases in Europe are usually caused by Babesia divergens. The
      spectrum of disease manifestation is broad, ranging from a silent infection to a
      fulminant, malaria-like disease, resulting in severe hemolysis and occasionally
      in death. Recent advances have resulted in the development of several diagnostic
      tests which have increased the level of sensitivity in detection, thereby
      facilitating diagnosis, expediting appropriate patient management, and resulting
      in a more accurate epidemiological description.

PMID- 10885992
TI  - Inhibition of brain Na(+),K(+)-ATPase activity in freshwater catfish (Channa
      punctatus bloch) exposed to paper mill effluent.

PMID- 10885993
TI  - Amphibian micronucleus test in vivo (Jaylet test) to evaluate the genotoxicity of
      petrochemical waste waters.

PMID- 10885994
TI  - Fish cytochrome P4501A1 activity induced by biobio river sediments, South Central
      Chile.

PMID- 10885995
TI  - Ecotoxicological assessment of two pulp mill effluent, Biobio River Basin, Chile.

PMID- 10885996
TI  - Prediction of octanol/water partitioning coefficient and sediment sorption
      coefficient for benzaldehydes by various molecular descriptors.

PMID- 10885997
TI  - Persistence and safety evaluation of alphamethrin on mustard (Brassica campestris
      linn.).

PMID- 10885998
TI  - Monitoring methyl parathion residues in milk and yogurt, and fate of [(14)C]
      methyl parathion during milk processing.

PMID- 10885999
TI  - Residues of amitraz, a new acaricide, on tea.

PMID- 10886000
TI  - Ca(2+) ultrastructural distribution in root apical cells of wheat under aluminum
      stress.

PMID- 10885988
TI  - Pathogenesis of group A streptococcal infections.
AB  - Group A streptococci are model extracellular gram-positive pathogens responsible
      for pharyngitis, impetigo, rheumatic fever, and acute glomerulonephritis. A
      resurgence of invasive streptococcal diseases and rheumatic fever has appeared in
      outbreaks over the past 10 years, with a predominant M1 serotype as well as
      others identified with the outbreaks. emm (M protein) gene sequencing has changed
      serotyping, and new virulence genes and new virulence regulatory networks have
      been defined. The emm gene superfamily has expanded to include antiphagocytic
      molecules and immunoglobulin-binding proteins with common structural features. At
      least nine superantigens have been characterized, all of which may contribute to
      toxic streptococcal syndrome. An emerging theme is the dichotomy between skin and
      throat strains in their epidemiology and genetic makeup. Eleven adhesins have
      been reported, and surface plasmin-binding proteins have been defined. The strong
      resistance of the group A streptococcus to phagocytosis is related to factor H
      and fibrinogen binding by M protein and to disarming complement component C5a by
      the C5a peptidase. Molecular mimicry appears to play a role in autoimmune
      mechanisms involved in rheumatic fever, while nephritis strain-associated
      proteins may lead to immune-mediated acute glomerulonephritis. Vaccine strategies
      have focused on recombinant M protein and C5a peptidase vaccines, and mucosal
      vaccine delivery systems are under investigation.

PMID- 10886001
TI  - Photochemical and microbial degradation of 2,4,6-trinitrotoluene (TNT) in a
      freshwater environment.

PMID- 10886002
TI  - Distribution of polycyclic aromatic hydrocarbons in a municipal solid waste
      landfill and underlying soil.

PMID- 10886003
TI  - Determination of organochlorine compounds (OCPs and PCBs) in fish oil and fish
      liver oil by capillary gas chromatography and electron capture detection.

PMID- 10886004
TI  - Hydrocarbon contamination in sediments of Nueces Bay, Texas.

PMID- 10886005
TI  - Anomalous trace element composition of coastal sediments near the copper mining
      district of Santa Rosalia, peninsula of Baja California, Mexico.

PMID- 10886006
TI  - Heavy metals in various molluscs from the Mauritanian coast.

PMID- 10886007
TI  - Special issue: Chemical mutagenesis in mice.

PMID- 10886008
TI  - Genomics meets genetics: towards a mutant map of the mouse.
AB  - Phenotype-driven mutagenesis approaches in the mouse will deliver a vastly
      expanded mouse mutant resource and can be expected to lead to the identification
      of novel genes and pathways, enabling the emergence of new insights into
      mammalian gene function. In order for this goal to be realized, developments in
      genomics need to be harnessed to progress in mouse mutagenesis. We need firstly
      to generate a mutant map of the mouse, devising and employing rapid methods for
      the genetic mapping of the growing mouse mutant resource. Secondly, we need to be
      able to rapidly identify and assess candidate genes in the vicinity of the mapped
      mutations. Developments in mapping and genotyping technology are described that
      will potentially speed the construction of a rich mutant map of the mouse. In
      addition, the benefits of comparative sequencing of the human and mouse genomes
      are reviewed. The availability of both human and mouse genome sequences will
      underpin the evolution of a comprehensive and well annotated mammalian gene map
      that will significantly enhance our ability to move rapidly from mapped mutation
      to the identification of the underlying gene.

PMID- 10886009
TI  - The mutagenic action of N-ethyl-N-nitrosourea in the mouse.

PMID- 10886010
TI  - Effects of ENU dosage on mouse strains.
AB  - The germline supermutagen, N-ethyl-N-nitrosourea (ENU), has a variety of effects
      on mice. ENU is a toxin and carcinogen as well as a mutagen, and strains differ
      in their susceptibility to its effects. Therefore, it is necessary to determine
      an appropriate mutagenic, non-toxic dose of ENU for strains that are to be used
      in experiments. In order to provide some guidance, we have compiled data from a
      number of laboratories that have exposed male mice from inbred and non-inbred
      strains or their F(1) hybrids to ENU. The results show that most F(1) hybrid
      animals tolerate ENU well, but that inbred strains of mice vary in their
      longevity and in their ability to recover fertility after treatment with ENU.

PMID- 10886011
TI  - Developing genetic reagents to facilitate recovery, analysis, and maintenance of
      mouse mutations.
AB  - Because the mouse has become the pre-eminent model system for functional genomics
      and analysis of complex-systems/pathways in mammals, there has been an escalation
      of interest in the generation and analysis of mouse mutations to use as tools in
      these analyses. I argue here for a parallel investment in continuing the
      development of appropriately marked chromosomal rearrangements to use as genetic
      reagents in mutation recovery, analysis, and maintenance crosses. Specifically,
      visibly marked interstitial chromosomal deletions can be valuable for regional
      mutagenesis screens for recessives based on hemizygosity, and they can also be
      used to simplify genetic fine-mapping as a prelude to gene identification based
      on positional cloning/candidacy strategies. Dominantly marked chromosomal
      inversions that also manifest some kind of recessive phenotype can be exploited
      in more extensive regional mutagenesis screens based on homozygosity, and are
      invaluable for simplified, low-cost and error-reduced mutant-stock maintenance.
      Also discussed are several issues concerning genetic background, particularly
      from the point of view of genetic-reagent resource development.

PMID- 10886012
TI  - Implementation of a large-scale ENU mutagenesis program: towards increasing the
      mouse mutant resource.
AB  - Systematic approaches to mouse mutagenesis will be vital for future studies of
      gene function. We have begun a major ENU mutagenesis program incorporating a
      large genome-wide screen for dominant mutations. Progeny of ENU-mutagenized mice
      are screened for visible defects at birth and weaning, and at 5 weeks of age by
      using a systematic and semi-quantitative screening protocol-SHIRPA. Following
      this, mice are screened for abnormal locomotor activity and for deficits in
      prepulse inhibition of the acoustic startle response. Moreover, in the primary
      screen, blood is collected from mice and subjected to a comprehensive clinical
      biochemical analysis. Subsequently, secondary and tertiary screens of increasing
      complexity can be used on animals demonstrating deficits in the primary screen.
      Frozen sperm is archived from all the male mice passing through the screen. In
      addition, tail tips are stored for DNA. Overall, the program will provide an
      extensive new resource of mutant and phenotype data to the mouse and human
      genetics communities at large. The challenge now is to employ the expanding mouse
      mutant resource to improve the mutant map of the mouse. An improved mutant map of
      the mouse will be an important asset in exploiting the growing gene map of the
      mouse and assisting with the identification of genes underlying novel mutations
      with consequent benefits for the analysis of gene function and the identification
      of novel pathways.

PMID- 10886014
TI  - ENU mutagenesis in zebrafish--from genes to complex diseases.

PMID- 10886013
TI  - The large-scale Munich ENU-mouse-mutagenesis screen.

PMID- 10886015
TI  - Saturation mutagenesis for dominant eye morphological defects in the mouse Mus
      musculus.
AB  - We have summarized our extensive series of mutagenesis experiments to isolate
      dominant mutations in the mouse that express eye morphological defects. Thirty
      two experimental groups in which parental mice were exposed to chemical mutagens
      or irradiation and a historical control group of the laboratory are presented.
      The largest series of experiments included parental exposure to ethylnitrosourea
      or irradiation. A total of 203 dominant mutants were confirmed among 456,890
      offspring screened, which represents one of the largest collections of mutations
      in the mouse affecting one organ following a systematic screen of offspring of
      mutagenized animals. The largest group of mutations (92) was recovered in
      offspring of parental mice exposed to ethylnitrosourea. The second largest group
      of mutations (62) was recovered in irradiation experiments. Fifty-six mutations
      recovered in ethylnitrosourea experiments have been mapped to 22 loci. The
      affected genes have been identified for a number of the recovered mutations
      including Cryga, Crygb, Cgyge, Pax6, Pax2, Mitf, Lim2, and Cx50. On the basis of
      our experiences, a number of considerations when undertaking such screens are
      discussed, including a) choice of mutagen, b) experimental design, and c) the
      criteria for such experiments to ensure that mutations at novel loci will be
      recovered.

PMID- 10886016
TI  - Identification of immunological relevant phenotypes in ENU mutagenized mice.
AB  - The immunology screen focuses on the identification of novel gene products
      involved in the mammalian immune response and on the establishment of mouse
      models for immunological disorders. For this purpose, high throughput and semi
      automated techniques were developed and optimized for low cost per sample and
      reproducibility. All assays are designed to be nonconsumptive and are based on
      peripheral blood or direct PCR amplification.

PMID- 10886017
TI  - Screening for dysmorphological abnormalities--a powerful tool to isolate new
      mouse mutants.

PMID- 10886018
TI  - Tests of the mouse visual system.
AB  - To apply the approach of forward genetics (e.g., gene identification with
      mutagenesis and screening, followed by positional cloning) to the mouse, it is
      necessary to have available screening tests that can be applied rapidly to
      individual mice and that give a reliable assessment of visual function. This
      paper reviews the strengths and limitations of two anatomical tests related to
      visual function, fundus examination and retinal histological examination. Two
      tests that do not depend on behavior of a conscious animal are reviewed: the
      electroretinogram and the visual evoked potentials of the cortex. Eight
      behavioral tests are also summarized: maze-based tests, cued fear conditioning,
      tests based on conditioned suppression, visual placing, optokinetic nystagmus,
      pupillary reflex, and light-induced shifts in circadian phase. It is recommended
      that retinal histology, the electroretinogram, and visual-evoked potentials be
      used at the present time for screening because they assess the function and
      structure of the visual system rapidly and reliably. In fact, the
      electroretinogram (or visually evoked potentials) can be recorded from several
      animals simultaneously in response to the same stimulus. It is also recommended
      that efforts be made to develop more appropriate, automated, behavioral tests of
      visual perception than are now available, particularly tests that rely solely on
      rewarding visually evoked behavior. Two other promising behavioral tests are cued
      fear conditioning and variants of maze tests.

PMID- 10886019
TI  - Enzyme-activity mutants in Mus musculus. I. Phenotypic description and genetic
      characterization of ethylnitrosourea-induced mutations.
AB  - The specific activity of erythrocyte enzymes was measured to detect gene
      mutations in F(1)-offspring of male mice treatment with different doses (80, 160,
      or 250 mg/kg body weight) of ethylnitrosourea (ENU). Altogether 13,230 offspring
      were screened for 10 enzyme activities. Mutants with reduced activity as well as
      mutants with enhanced activity were found. Of the 36 independently observed
      mutations, 20 were homozygous lethal. Genetic and biochemical characterizations
      were routinely performed. These mutants provide insight into the mechanism of ENU
      mutagenesis and can serve as models for structure-function studies of the
      corresponding enzymes.

PMID- 10886020
TI  - The clinical-chemical screen in the Munich ENU Mouse Mutagenesis Project:
      screening for clinically relevant phenotypes.

PMID- 10886021
TI  - The biochemical metabolite screen in the Munich ENU Mouse Mutagenesis Project:
      determination of amino acids and acylcarnitines by tandem mass spectrometry.
AB  - BACKGROUND: Gene mutations often result in altered protein expression and, in
      turn, lead to changes in metabolite levels in one or more distinct biochemical
      pathways. Traditional analytical methods for metabolite determination are usually
      time consuming, expensive, and, thus, not suitable for high throughput analysis.
      However, recent developments in electrospray-tandem-mass-spectrometry allow
      comprehensive metabolite scanning from very small amounts of blood with high
      speed, cost effectiveness, and accuracy. METHODS: A blood spot from a filter
      paper equivalent to 3 microl of blood was punched out and transferred to a 96
      well microtiter plate. After addition of a set of 14 stable isotope-labeled
      internal standards, amino acids and acylcarnitines were extracted with methanol.
      The dried residue was derivatized with butanolic hydrochloric acid and subjected
      to MSMS analysis. RESULTS: Acyl-carnitines were all determined by a precursor ion
      scan of 85 Da. Neutral loss scanning of 102 Da was suitable for the quantitation
      of threonine, serine, proline, histidine, alanine, aspartic acid, glutamic acid,
      methionine, tyrosine, phenylalanine, isoleucine/leucine and valine. Glycine was
      detected by a loss of a 56-Da fragment, whereas a 119-Da loss was suitable for
      the measurement of citrulline, ornithine, arginine, and lysine. Specific problems
      encountered: owing to their identical molecular weight, isoleucine and leucine
      could not be quantitated separately, and, owing to their instability, glutamine
      and asparagine were found to be decarboxylated to their respective acids.
      Determination was linear over the concentration range tested (20 to 1000
      micromol/L), and intraassay and interassay coefficients of variation were in the
      range of 10-15%. CONCLUSION: ESI-MSMS proved to be a highly sensitive, linear,
      and sufficiently precise method for the quantitative determination of amino acids
      and acylcarnitines in mouse blood, allowing large-scale screening applications
      when speed and cost effectiveness are mandatory.

PMID- 10886022
TI  - Comet assay as a tool to screen for mouse models with inherited radiation
      sensitivity.
AB  - Recent in vivo and in vitro data of patients analyzed for genetic susceptibility
      to radiation during cancer therapy have shown structural changes in the
      chromosomes to be prevalent both in the patients being treated and in their
      immediate family members. As structural changes in chromosomes frequently lead to
      activation of proto-oncogenes and elimination of tumor-suppressor genes, they
      represent important mechanisms for the initiation of DNA repair processes and
      tumorigenesis. With the exception of rare genetic syndromes such as AT (Ataxia
      telangiectasia) or NBS (Nijmegen Breakage Syndrome), the background for the
      inheritance of genetic susceptibility to radiation is unknown. Recently, a large
      scale genetic screen of mouse mutants has been established within the German
      Human Genome Project (Hrabe de Angelis and Balling 1998). The goal of this ENU
      (ENU: ethylnitrosourea) mutagenesis screen is the generation of mutant mice that
      will serve as animal models for human diseases and genetic susceptibility. In
      order to fully utilize the potential of a genetic screen of this magnitude, in
      which exploration for genes responsible for genomic instability and radiation
      sensitivity is to occur, it is necessary to establish a simple assay system that
      is amenable to automation. Hence, we are using the single-cell gel
      electrophoresis (comet assay) to detect mouse mutants that display a genetic
      susceptibility to ionizing radiation. We have established the analysis parameters
      in the comet assay which are currently used to detect radiation-sensitive mouse
      mutants and to control the variance within the mouse population in the ENU
      screen. The assay can be used to isolate genes that are responsible for DNA
      repair and radiation sensitivity in mouse and human.

PMID- 10886023
TI  - Behavior and mutagenesis screens: the importance of baseline analysis of inbred
      strains.
AB  - Random mutagenesis as a means of identifying the function of genes has been used
      extensively in a variety of model organisms. Until recently it has been used
      primarily in the identification of single-gene traits that cause visible and
      developmental mutations. However, this genetic approach also has the power to
      identify genes that control complex biological systems such as behavior.
      Mutagenesis screens for behavioral mutations require careful consideration of
      many factors, including choice of both assays and background strains for use in
      mutagenesis and subsequent mapping of the affected gene or genes. This paper
      describes behavioral assays for monitoring motor coordination on the accelerating
      rotarod, anxiety-related behaviors in the elevated zero maze and sensorimotor
      reactivity, gating, and habituation of acoustic startle. These five physiological
      or neurological behaviors can represent potential endophenotypes for a variety of
      neurological and psychiatric disorders. The significant degree of strain- and sex
      specific differences in the performance of four inbred strains of mice (C57BL/6J,
      C3HeB/FeJ, DBA/2J, and 129/SvlmJ) in these behavioral assays illustrates the
      importance of performing baseline analysis prior to behavioral mutagenesis
      screens and genetic mapping of selected mutations.

PMID- 10886024
TI  - Cryoconservation--archiving for the future.
AB  - Mouse genetics is set to play a pivotal role in the key post-genome challenge-the
      study of mammalian gene function. Addressing this challenge will involve the
      development and application of systematic mutagenesis approaches. The expanding
      mouse mutant resource that will result threatens to overwhelm the currently
      available animal facility space. Cryopreservation of both mouse embryos and
      spermatozoa is currently widely employed for the efficient archiving of mouse
      stocks. Distribution and dissemination of new and existing mouse strains is
      simplified by the availability of extensive frozen archives. Also, the
      availability of archives of frozen spermatozoa provides a potential powerful
      route for the production of backcross progeny for rapid genetic mapping.
      Moreover, frozen oocytes and ovaries may offer a valuable addition to the current
      cryopreservation approaches. Comprehensive mouse mutant archives will provide an
      essential resource for mammalian genetics throughout the 21(st) century.

PMID- 10886025
TI  - Cryopreservation of mouse spermatozoa.
AB  - Recently, it has become possible to freeze a large number of mouse spermatozoa
      immediately after collection from the epididymides of a small number of males.
      The cryopreservation of spermatozoa is simpler, less time-consuming, and less
      costly than that of embryos for maintaining various strains of mice with induced
      mutations. This chapter attempts to provide a realistic overview of the
      cryopreservation of mouse spermatozoa and to describe a detailed procedure for
      mouse sperm freezing.

PMID- 10886026
TI  - Informatics for mutagenesis: the design of mutabase--a distributed data recording
      system for animal husbandry, mutagenesis, and phenotypic analysis.
AB  - The increasing use of high-throughput methods for the production of biologically
      important information and the increasing diversity of that information pose
      considerable bioinformatics challenges. These challenges will be met by
      implementing electronic data management systems not only to capture the data, but
      increasingly to provide a platform for data integration and mining as we enter
      the post-genomic era. We discuss the design and implementation of such a data
      capture system, 'Mutabase', as a model of how such electronic systems might be
      designed and implemented. Mutabase was created in support of a large-scale,
      phenotype-driven mouse mutagenesis program at MRC Mammalian Genetics Unit,
      Harwell, in collaboration with SmithKline Beecham Pharmaceuticals, Queen Mary and
      Westfield College, London, and Imperial College of Science, Technology and
      Medicine, London. The aim of this mutagenesis project is to make a significant
      contribution to the existing mouse mutant resource, closing the phenotype gap and
      providing many more models for fundamental research and disease modeling.
      Mutabase records experimental details at the 'point of generation' and provides a
      number of dissemination and analysis tools for the experimental data, as well as
      providing a means of assessing various aspects of progress of the program.
      Mutabase uses a hypertext-based interface to provide interaction between a number
      of intranet-based client workstations and a central industrial strength database.
      Mutabase utilizes a variety of techniques in order to implement the user
      interface system including Perl/CGI, Java Servlets, and an experimental CORBA
      server. We discuss the relative merits of these methods in the context of the
      need to provide sound informatics approaches for the support of systematic
      mutagenesis programs.

PMID- 10886027
TI  - Algorithms for mutant sorting: the need for phenotype vocabularies.
AB  - For effectively annotated phenotypes for mouse, a number of detailed phenotypic
      classification systems are needed. The rapidly increasing number of
      phenotypically described characteristics of both normal and mutant mice are
      providing a rich data set for comparison and analysis. However, we cannot rely on
      text descriptions that are subject to the word-usage style of the writer if we
      are to do large-scale comparative analysis of traits and diseases. The rationale
      for developing vocabularies and examples of several vocabularies being developed
      are described. Finally, the critical nature of community participation in both
      building and applying phenotype vocabularies is discussed.

PMID- 10886028
TI  - MouseNet database: digital management of a large-scale mutagenesis project.
AB  - The Munich ENU Mouse Mutagenesis Screen is a large-scale mutant production,
      phenotyping, and mapping project. It encompasses two animal breeding facilities
      and a number of screening groups located in the general area of Munich. A central
      database is required to manage and process the immense amount of data generated
      by the mutagenesis project. This database, which we named MouseNet(c), runs on a
      Sybase platform and will finally store and process all data from the entire
      project. In addition, the system comprises a portfolio of functions needed to
      support the workflow management of the core facility and the screening groups.
      MouseNet(c) will make all of the data available to the participating screening
      groups, and later to the international scientific community. MouseNet(c) will
      consist of three major software components:* Animal Management System (AMS)*
      Sample Tracking System (STS)* Result Documentation System (RDS)MouseNet(c)
      provides the following major advantages:* being accessible from different client
      platforms via the Internet* being a full-featured multi-user system (including
      access restriction and data locking mechanisms)* relying on a professional RDBMS
      (relational database management system) which runs on a UNIX server platform*
      supplying workflow functions and a variety of plausibility checks.

PMID- 10886029
TI  - Sequence-based analysis of mutagenized mice.
AB  - Treating mice with ethylnitrosourea (ENU) is an efficient means for mutagenizing
      spermatogonial cells, and this treatment has been proven effective in a variety
      of screens for both dominant and recessive mutations. However, a significant
      problem for this technology is that the efficiency of mutagenesis is assessed
      most often by the empiric determination of a per-locus mutation frequency by
      using the specific locus test, which is expensive, time-consuming, and
      logistically difficult. To approach this question more directly and more
      efficiently, one can utilize methods of PCR-based mutation detection for the
      characterization of progeny of mutagenized mice. Since this analysis can be done
      after a single generation of breeding, it is useful as a rapid means for the
      assessment of the efficiency of mutagen treatment. Furthermore, it is readily
      imaginable that this strategy can be applied for the general determination of
      gene function in a systematic manner. Theoretical considerations and empirical
      analysis suggest that the per-base mutation frequency for a fractionated-dose
      treatment protocol is on the order of 1 sequence change per 10(5) bp.

PMID- 10886030
TI  - Toward the yeastification of mouse genetics: chemical mutagenesis of embryonic
      stem cells.

PMID- 10886031
TI  - Muta-genetics or muta-genomics: the feasibility of large-scale mutagenesis and
      phenotyping programs.

PMID- 10886032
TI  - Hyperglycaemia alters the endothelium-dependent relaxation of canine coronary
      arteries.
AB  - The aim of the present study was to investigate the effects of experimental
      diabetes and hyperglycaemia per se on the endothelium-dependent relaxation of
      isolated canine coronary arteries and to analyse the possible involvement of the
      cyclooxygenase pathway in the alterations induced by hyperglycaemia. Rings from
      the left anterior descending coronary arteries of 18 metabolically healthy, six
      alloxan-diabetic and six insulin-treated alloxan diabetic dogs were set up for
      isometric tension recording. Diabetic coronaries as well as healthy vessels
      subjected to in vitro hyperglycaemia (25.5 mmol L-1 glucose) showed impaired (P <
      0.05) relaxation to acetylcholine (3 nmol L-1-10 micromol L-1) compared with
      normoglycaemic, i.e. metabolically healthy and insulin-treated diabetic controls,
      either before or after indomethacin (3 micromol L-1) administration. The maximal
      dilation elicited by acetylcholine was further decreased (P < 0.05) by the
      cyclooxygenase inhibitor in the diabetic coronaries only. Relaxation to sodium
      nitroprusside did not differ among groups. These results suggest that
      hyperglycaemia may result in impaired endothelium-dependent dilation of coronary
      arteries. Diminished relaxation of diabetic coronaries is worsened by the
      inhibition of the synthesis of vasodilator cyclooxygenase products.

PMID- 10886033
TI  - Influence of neurohumoral blockade on heart rate and blood pressure responses to
      haemorrhage in isoflurane anaesthetized rats.
AB  - Four groups of Sprague-Dawley rats were anaesthetized with isoflurane (ISO) (1.7%
      end-tidal concentration) in 40% oxygen, and mechanically ventilated. The animals
      were bled 15 mL kg-1 b.w. from the femoral vein over 10 min, followed by an
      observation period of 30 min. Ten minutes before haemorrhage each group of
      animals was pre-treated with intravenous injection/infusion of either: isotonic
      saline (Group B; CON; n=7), vasopressin V1-receptor antagonist
      [d(CH2)5Tyr(Me)AVP; 10 microg kg-1] (Group C; AVP-a; n=7), the non-selective
      angiotensin II receptor antagonist saralasin (10 microg kg-1 min-1) (Group D;
      SAR; n=7) or hexamethonium (10 mg kg-1) (Group E; HEX; n=7). A separate group of
      conscious animals were pre-treated with isotonic NaCl and subjected to the same
      haemorrhage protocol (Group A; AW; n=7). Mean arterial pressure (MAP), heart rate
      (HR) and blood gases were observed during the experiments. Only pre-treatment
      with SAR and HEX reduced MAP significantly. The pre-haemorrhage HR was only
      affected by HEX, which caused a reduction by 17%. The HR was significantly lower
      at the end of haemorrhage compared with pre-haemorrhage levels in all groups
      except that group treated with HEX. In that group the HR changed in the opposite
      direction. The ability to maintain MAP during haemorrhage, and the post
      haemorrhage period, was significantly impaired in the groups treated with AVP-a,
      SAR or HEX compared with the group receiving NaCl. It is concluded that autonomic
      nervous activity is of major importance for the maintenance of MAP during
      isoflurane anaesthesia, whereas circulating angiotensin II and vasopressin levels
      contribute to a much smaller degree in this regard. General anaesthesia in
      combination with different degrees of neurohumoral blockade impairs the
      haemodynamic responses to blood loss, seen in conscious individuals. The
      impairment involves both the early and late phases during haemorrhage, as well as
      the post-bleeding recovery period. All three neurohumoral systems (autonomic
      nervous activity, angiotensin II and vasopressin) are of importance for
      regulating MAP during and after haemorrhage, although the autonomic nervous
      outflow appears to contribute to a larger extent.

PMID- 10886034
TI  - Effects on infarct size and on arrhythmias by controlling reflow after myocardial
      ischaemia in pigs.
AB  - Part of the myocardial damage after an ischaemic period might be related to the
      reperfusion conditions. Many abrupt changes occurring in the heart during
      reperfusion may add to the damage during the preceding ischaemic period, and
      increase in infarct size. In this study we tested the hypothesis that infarct
      size and occurrence of ventricular arrhythmias might be reduced by restricting
      reflow after an ischaemic period. Seventeen pigs underwent 45 min of total
      occlusion of the left anterior descending coronary artery with an hydraulic
      occluder. In the intervention group reperfusion was restricted to 50% of baseline
      during the first minute, to 100% during the next minute, kept constant for 1 min,
      and thereafter allowed to increase by 50% of baseline flow every minute until
      free reflow. In the control group reflow was not restricted. Arrhythmias were
      recorded. After 2.5 h of reperfusion the heart was excised. Infarct size was
      measured by using triphenyltetrazolium chloride (delineation of necrosis),
      fluorescent microspheres (delineation of area at risk) and planimetry. No
      reduction in infarct size (% of area at risk) was found between the intervention
      group and the control group (75.9 +/- 5.3% vs. 72.4 +/- 4.3%). The incidence of
      ventricular arrhythmias and ventricular fibrillation were not found to be
      different between the groups during reperfusion. Hemodynamic parameters were not
      significantly different between the two groups. Our data indicate that no
      substantial protection against myocardial infarct or ventricular arrhythmias
      could be achieved by controlling reflow using the present protocol after a period
      of myocardial ischaemia in pigs. Accordingly, our data do not support the notion
      that control of reflow may be beneficial when treating coronary artery occlusion
      with percutaneous coronary angioplasty (PCA).

PMID- 10886035
TI  - Ruled by waves? Intracellular and intercellular calcium signalling.
AB  - The field of calcium signalling has evolved rapidly the last 20 years.
      Physiologists had worked with cytosolic Ca2+ as the coupler of excitation and
      contraction of muscles and as a secretory signal in exocrine glands and in the
      synapses of the brain for several decades before the discovery of cellular
      calcium as a second messenger. Development of powerful techniques for measuring
      the concentration of cytosolic free calcium ions in cell suspensions and later in
      single cells and even in different cellular compartments, has resulted in an
      upsurge in the knowledge of the cellular machinery involved in intracellular
      calcium signalling. However, the focus on intracellular mechanisms might have led
      this field of study away from physiology. During the last few years there is an
      increasing evidence for an important role of calcium also as an intercellular
      signal. Via gap junctions calcium is able to co-ordinate cell populations and
      even organs like the liver. Here we will give an overview of the general
      mechanisms of intracellular calcium signalling, and then review the recent data
      on intercellular calcium signals. A functional coupling of cells in different
      tissues and organs by the way of calcium might be an important mechanism for
      controlling and synchronizing physiological responses

PMID- 10886036
TI  - Modulation of Na(+) x H(+) exchange by osmotic shock in isolated bovinearticular
      chondrocytes.
AB  - The effects of hyperosmotic shock on intracellular pH (pHi) have been
      characterized in bovine articular chondrocytes. Osmotic shock is one of a variety
      of physicochemical stimuli experienced by chondrocytes upon cartilage loading.
      Cells were isolated from their extracellular matrix, and loaded with the pH
      sensitive fluorophore 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein.
      Hyperosmotic shocks were imposed by addition of KCl or sucrose to the
      extracellular medium. For cells at steady-state pHi, resuspension in hyperosmotic
      solutions elicited an alkalinization, which was significantly inhibited by
      removal of extracellular Na+ ions, or treatment with amiloride (1 mM) or HOE-694
      (10 microM), both inhibitors of Na+ x H+ exchange. For cells acidified by
      ammonium rebound, recovery of pHi towards resting levels was significantly
      stimulated by exposure to hyperosmotic solutions, and the effect was again
      attenuated by inhibition of Na+ x H+ exchange. Determination of the rate of acid
      extrusion at different levels of acidification indicated that the affinity of
      acid extrusion systems for H+ ions was increased by hypertonic shock. The
      response to hyperosmotic media could be abolished by treatment of chondrocytes
      with the non-specific kinase inhibitor staurosporine (10 nM), while the
      phosphatase inhibitor okadaic acid (1 mM) was able to augment recovery rates to
      values similar to those measured under hyperosmotic conditions. The osmotic
      sensitivity of recovery was unaffected by exposure to the protein kinase C
      inhibitor calphostin C, but was abolished in cells treated with ML-7, a specific
      inhibitor of myosin light chain kinase. These results confirm that - as for other
      components of mechanical load - increased osmolarity can modulate the activity of
      Na+ x H+ exchange, in this case by altered patterns of phosphorylation of
      transporter-associated myosin. The changes of pHi which will result dictate in
      part the rate of cartilage macromolecule synthesis.

PMID- 10886037
TI  - Interaction of nitric oxide and reactive oxygen species on rat diaphragm
      contractility.
AB  - Growing evidence indicates that reactive oxygen species (ROS) as well as nitric
      oxide (NO) have a profound influence on contractile function of skeletal muscle
      possibly through modulation of excitation-contraction coupling. We hypothesized
      that if NO and xanthine oxidase (XO) interact at key sites in excitation
      contraction coupling, the effects of XO with nitric oxide synthase (NOS)
      inhibitors and NO donors on contractile function of the unfatigued diaphragm
      would not be additive. Diaphragm fibre bundles were extracted from 4-month
      Fischer-344 rats and placed in Krebs solution bubbled with 95% O2, 5% CO2.
      Baseline twitch tension, tension at 20 Hz (low-frequency), and maximal tetanic
      tension (Po) at 120 Hz were then measured (PRE). In Experiment 1 diaphragm fibre
      bundles were exposed to Krebs with 200 microM hypoxanthine as a control (CON);
      0.02 U mL-1 XO + 200 microM hypoxanthine; 1 mM of the NOS inhibitor N-nitro-L
      arginine (L-NNA) or L-NNA + XO. Five minutes were allowed for equilibration, and
      a second set of contractile measures was taken (POST). In Experiment 2 we exposed
      diaphragm fibre bundles to one of the following four solutions: CON, XO, 100
      microM of the NO donor sodium nitroprusside (SNP) and XO + SNP, and evaluated
      contractile function as described above. In Experiment 3 we tested to determine
      if peroxynitrite production from the reaction of superoxide anion and NO affected
      the above results for SNP using 30 microM ebselen as a peroxynitrite quencher.
      Xanthine oxidase resulted in a significant potentiation of diaphragm twitch
      tension and tension at 20 Hz (+29%) without affecting Po. L-NNA also
      significantly increased 20 Hz tension but did not alter Po. However, the
      combination of XO + L-NNA did not further increase low-frequency contractility.
      Sodium nitroprusside alone did not affect diaphragm contractility, but did
      attenuate XO-induced potentiation in the XO + SNP group. Ebselen did not alter
      the impact of SNP on XO in the diaphragm. These data support the hypothesis that
      XO and NO interact or compete at similar sites of action that modulate
      contractility of the unfatigued diaphragm.

PMID- 10886038
TI  - Nitric oxide prevents rat duodenal contractions induced by potentially noxious
      agents.
AB  - After abdominal surgery, luminal HCl fails to induce duodenal contractions in
      anaesthetized rats. Elevated tissue levels of nitric oxide (NO) and
      prostaglandins possibly contribute to this observation. The aim of this study was
      to compare the effects of luminal capsaicin (1.2 mg mL-1), ethanol (15%) and high
      partial pressure of CO2 (>250 mmHg) with those of HCl (10 mM) in anaesthetized
      rats. Motility (intraluminal pressure), mucosal permeability [blood-to-lumen
      clearance of 51Cr-EDTA (51Chromium-labelled ethylenediaminetetraacetate)] and
      duodenal mucosal bicarbonate secretion (DMBS) were recorded. Three groups of
      animals were studied: (1) controls, (2) pretreatment with the NO synthase
      inhibitor N-nitro-L-arginine-methyl-ester (L-NAME) and (3) pretreatment with the
      cyclo-oxygenase inhibitor indomethacin. Neither capsaicin, ethanol, CO2 nor HCl
      induced duodenal contractions or affected DMBS in control rats. However, L-NAME
      induced duodenal contractions that were augmented by capsaicin, ethanol and HCl,
      but not by CO2. Indomethacin also induced contractions that were reversibly
      diminished by capsaicin and HCl, but not by ethanol or CO2. Significant increases
      in mucosal permeability occurred during ethanol perfusion in indomethacin- and L
      NAME pretreated rats. In conclusion, NO probably plays a key role in preventing
      duodenal contractions in response to luminally HCl, capsaicin and ethanol. The
      HCl-induced effect on motility appears to be independent of CO2 and is not caused
      by alteration in mucosal integrity.

PMID- 10886039
TI  - Modification of the Xenopus electroretinogram by actions of glycine in the
      proximal retina.
AB  - The electroretinogram (ERG) was recorded from the Xenopus retina, to examine the
      effects of glycine and strychnine on these responses and to determine the origins
      of these changes. Glycine at concentrations between 0.1 and 10 mM reduced the b-
      and d-waves of the ERG in a dose-dependent manner, while strychnine increased
      their amplitude. 2-Amino-4-phosphonobutyric acid (APB) reduced the b-wave and
      blocked the effect of glycine, but not strychnine, on the d-wave. When the d-wave
      had first been blocked by kynurenic acid (KYN) or reduced by (+/-)cis-2,3
      piperidine dicarboxylic acid (PDA) the b-wave was enhanced by glycine, but not by
      strychnine. N-methyl-DL-aspartate (NMDLA), which alters responses in the proximal
      retina only, blocked the effects of glycine and strychnine on the ERG. This
      suggests that the glycinergic effects on the ERG are at least partly mediated by
      processes in the proximal retina. The results further support the suggestion that
      inhibitory neurotransmitters in the proximal retina may modulate both the b- and
      d-waves of the Xenopus ERG.

PMID- 10886040
TI  - Review article: primary prophylaxis for portal hypertensive bleeding in
      cirrhosis.
AB  - Variceal bleeding is a consequence of portal hypertension, which in turn is the
      major complication of hepatic cirrhosis. Given the high rate of mortality of the
      first bleeding episode, primary prophylaxis to prevent bleeding from varices and
      portal hypertensive gastropathy is the current optimal therapeutic approach. The
      difficulty in identification of patients with varices who will bleed, before they
      do so, can justify a strategy of treating all patients with varices
      prophylactically. We evaluated the various therapies that have been assessed in
      randomized controlled trials for prevention of first bleeding, using meta
      analysis where applicable. The current first choice treatment is non-selective
      beta-blockers; it is cheap, easy to administer, and is effective in preventing
      the first variceal haemorrhage and bleeding from gastric mucosa. Combination drug
      therapy of beta-blockers and nitrates looks promising, but needs further
      evaluation in randomized controlled trials. The conflicting results of the
      randomized studies of endoscopic banding ligation and the small number of
      patients and clinical events, as well as the cost, do not warrant any change in
      current practice. However, endoscopic banding ligation may be a reasonable
      alternative for patients who cannot tolerate, or have contraindications to beta
      blockers or no haemodynamic response to the drug therapy, but this must be proved
      in randomized trials.

PMID- 10886041
TI  - Esomeprazole provides improved acid control vs. omeprazole In patients with
      symptoms of gastro-oesophageal reflux disease.
AB  - BACKGROUND: Esomeprazole (Nexium) is a new proton pump inhibitor for the
      treatment of acid-related diseases. METHODS: In this double-blind crossover
      study, 38 patients with gastro-oesophageal reflux disease (GERD) symptoms were
      randomized to esomeprazole 40 and 20 mg and omeprazole 20 mg once daily for 5
      days. On day 5 of each dosing period, 24-h intragastric pH and pharmacokinetic
      variables were measured. RESULTS: Thirty-six patients aged 29-58 (mean 45) years
      completed the study. Esomeprazole 40 and 20 mg maintained intragastric pH > 4 for
      (mean) 16.8 and 12.7 h, respectively, vs. 10.5 h for omeprazole 20 mg (P < 0.001
      and P < 0. 01). Twenty-four-hour median intragastric pH was significantly higher
      with esomeprazole 40 mg (4.9) and 20 mg (4.1) than with omeprazole 20 mg (3.6) (P
      < 0.001 and P < 0.01). Area under the plasma concentration-time curve (AUC) was
      80% higher for esomeprazole 20 mg vs. omeprazole, while that for esomeprazole 40
      mg was more than five times higher (each P < 0.0001). Interpatient variability in
      intragastric pH and AUC was less with esomeprazole than with omeprazole.
      Esomeprazole was well tolerated and there were no safety concerns. CONCLUSIONS:
      Esomeprazole provides more effective acid control than omeprazole, with reduced
      interpatient variability, thereby offering the potential for improved efficacy in
      acid-related diseases.

PMID- 10886042
TI  - Effects of alosetron on gastrointestinal transit time and rectal sensation in
      patients with irritable bowel syndrome.
AB  - BACKGROUND: Alosetron, a 5-HT3-receptor antagonist, relieves abdominal pain and
      improves bowel function in non-constipated, female patients with irritable bowel
      syndrome. 5-HT3 antagonists delay colonic transit, increase colonic compliance,
      and increase small intestinal water absorption. AIM: To evaluate the effects of
      alosetron on gastrointestinal and colonic transit, rectal compliance and rectal
      sensation in irritable bowel syndrome. METHODS: A double-blind, placebo
      controlled, two-dose study of alosetron was performed in 25 non-constipated
      irritable bowel syndrome patients, with paired studies before and after 4 weeks
      of treatment with placebo (n=5), 1 mg alosetron (n=10) or 4 mg (n=10) alosetron
      b.d. Gastrointestinal and colonic transit were measured by scintigraphy. Rectal
      compliance and sensation were assessed by rectal balloon distention with a
      barostat. RESULTS: There was a trend (P=0.06) for 1 mg alosetron to increase
      rectal compliance (median pressure at half maximum volume 11 mmHg after alosetron
      vs. 15.6 mmHg before alosetron). The 1 mg b.d. alosetron dose non-significantly
      retarded proximal colonic transit. Alosetron and placebo reduced sensory scores
      relative to baseline values; none of the changes induced by alosetron was
      significant relative to placebo. CONCLUSIONS: Alosetron had no significant effect
      on gastrointestinal transit or rectal sensory and motor mechanisms in non
      constipated irritable bowel syndrome patients in this study. Alosetron's effects
      on colonic sensorimotor function and central sensory mechanisms deserve further
      evaluation.

PMID- 10886043
TI  - Interaction of Helicobacter pylori eradication and non-steroidal anti
      inflammatory drugs on gastric epithelial apoptosis and proliferation:
      implications on ulcerogenesis.
AB  - BACKGROUND: Apoptosis is associated with loss of gastric mucosal integrity and
      may play an important role in ulcer development. AIM: To examine how Helicobacter
      pylori and NSAIDs interact to effect apoptosis and proliferation of the gastric
      mucosa. METHODS: Patients presenting with musculoskeletal pain requiring NSAID
      treatment and without previous exposure to NSAID or pre-existing ulcers were
      recruited. Patients were divided into three groups: (A) H. pylori-infected; (B)
      H. pylori-eradicated; and (C) non-infected patients. They were given naproxen for
      8 weeks. Patients with non-ulcer dyspepsia and H. pylori infection who were given
      anti-Helicobacter therapy were recruited as controls (D). Endoscopy was performed
      at baseline and 8-weeks after receiving naproxen. Gastric antral biopsies were
      obtained to assess apoptosis by terminal uridine deoxynucleotidyl nick end
      labelling (TUNEL) and proliferation by Ki67 immunostaining. RESULTS: A total of
      55 patients were studied. H. pylori-positive patients had a higher apoptosis and
      proliferation index at baseline than non-infected patients (P < 0.0001), and
      eradication of H. pylori resulted in a significant reduction in these parameters.
      The NSAID induced apoptosis in non-infected subjects (P=0.03) whilst apoptosis
      was reduced in H. pylori-positive patients receiving NSAID (P=0.02). After 8
      weeks of NSAID, post-treatment apoptosis was significantly higher in patients
      with persistent H. pylori infection than in non-infected patients (P=0.01).
      CONCLUSIONS: Eradication of H. pylori prior to NSAID therapy significantly
      reduces the level of apoptosis in the gastric mucosa, which may contribute to
      maintaining mucosa integrity and preventing ulcer development.

PMID- 10886044
TI  - Oral pharmacokinetics of omeprazole and lansoprazole after single and repeated
      doses as intact capsules or as suspensions in sodium bicarbonate.
AB  - BACKGROUND: Omeprazole and lansoprazole can be given in sodium bicarbonate as,
      respectively, simplified omeprazole suspension and simplified lansoprazole
      suspension. We previously found the antisecretory effect of omeprazole 20 mg
      given as simplified omeprazole suspension to be lower than with intact capsules.
      However, lansoprazole 30 mg as simplified lansoprazole suspension produced an
      effect similar to that seen with intact capsules. AIM: To evaluate the absorption
      of both drugs when given orally as capsules or as suspensions in sodium
      bicarbonate. METHODS: In random order, we gave 5-day courses of omeprazole 20 mg
      and lansoprazole 30 mg as capsules and as suspensions in sodium bicarbonate to 12
      healthy women. Serial blood samples were taken on days 1 and 5 of each course for
      pharmacokinetic measurements. RESULTS: There was impairment of omeprazole
      absorption when given as simplified omeprazole suspension. Maximum plasma
      concentration and area under the concentration/time curve were lower with
      simplified omeprazole suspension than with omeprazole capsules (P=0.034 and
      0.013, respectively, on day 5). No differences were found in lansoprazole
      absorption when simplified lansoprazole suspension was compared with its standard
      capsule formulation. Relative bioavailability of omeprazole from simplified
      omeprazole suspension compared to the capsule was 58.4% on day 5. The
      corresponding value for lansoprazole was 84.7%. CONCLUSIONS: Simplified
      omeprazole suspension 20 mg does not supply adequate omeprazole for systemic
      absorption. Lansoprazole absorption from simplified lansoprazole suspension is
      maintained.

PMID- 10886045
TI  - The impact of antibiotic resistance on the efficacy of three 7-day regimens
      against Helicobacter pylori.
AB  - BACKGROUND: Antibiotic resistance affects the success of anti-Helicobacter pylori
      therapies and varies greatly from country to country. AIM: To compare the
      efficacy of three short-term triple regimens in relation to H. pylori primary
      resistance in our region. METHODS: We enrolled 210 H. pylori-positive dyspeptic
      patients for this randomized, open, parallel-group study. Three arms of 70
      patients each received the following 1-week regimens: (1) ranitidine bismuth
      citrate 400 mg b.d. + clarithromycin 250 mg b.d. + metronidazole 500 mg b.d.
      (RCM); (2) bismuth subcitrate 240 mg b.d. + amoxycillin 1000 mg b.d. +
      metronidazole 500 mg b.d. (BAM); (3) omeprazole 20 mg o.d. + clarithromycin 250
      mg b.d. + metronidazole 500 mg b.d. (OCM). H. pylori was assessed by CLO-test and
      histology before and 4 weeks after therapy. Antibiotic resistance was assessed by
      E-test. RESULTS: On intention-to-treat analysis RCM was more effective than OCM
      (84% vs. 69%; P < 0.03) and BAM (84% vs. 63%; P < 0.004). MIC determination was
      successful in 117 out of 210 patients (55%); metronidazole resistance was present
      in 52 out of 117 patients (44%) and clarithromycin resistance was present in 17
      out of 117 patients (14%). Excellent cure rates were achieved when strains were
      sensitive to both antibiotics (100% with RCM and BAM and 90% with OCM), whereas
      RCM was superior to OCM (P=0.009) and BAM (P=0.001) with respect to overall
      resistant strains (94% vs. 57% and 38%, respectively). CONCLUSIONS: One-week RCM
      is the best regimen to eradicate H. pylori in our geographical area. This seems
      to be linked to the better ability of RCM compared to OCM and BAM in overcoming
      the high prevalence of H. pylori resistance to both metronidazole and
      clarithromycin in our region.

PMID- 10886046
TI  - High prevalence of Helicobacter pylori infection with dual resistance to
      metronidazole and clarithromycin in Hong Kong.
AB  - BACKGROUND: Metronidazole resistance is a common problem in most Asian countries,
      and clarithromycin has been widely used in Hong Kong. AIM: To determine the
      prevalence of Helicobacter pylori strains resistant to metronidazole and
      clarithromycin in Hong Kong and to assess the effect on eradication rates. Also
      to determine the genetic mutation in relation to phenotypic divergence in
      clarithromycin-resistant strains. METHODS: H. pylori were cultured from gastric
      biopsies obtained from 87 patients during upper endoscopy. Minimal inhibitory
      concentrations of metronidazole and clarithromycin were determined by Etest and
      agar dilution methods. Mutations in clarithromycin-resistant strains were
      identified by polymerase chain reaction and restriction analysis. Random
      amplified polymorphic DNA fingerprinting was performed on clarithromycin
      resistant and susceptible isolates. RESULTS: The prevalences of H. pylori strains
      resistant to metronidazole and clarithromycin were 49.4% and 10.8%, respectively,
      in Hong Kong. Dual resistance to metronidazole and clarithromycin were found in
      7. 2% of patients. The agreement between E-test and agar dilution methods was
      determined by error-rate bound analysis as 95.4% for metronidazole and 100% for
      clarithromycin. Dual resistant strains reduced the eradication rate to 66.7%.
      Among clarithromycin-resistant strains tested, all were due to A2144G point
      mutation in 23S rRNA gene. Random amplified polymorphic DNA fingerprinting
      suggested various phenotypically mixed populations. CONCLUSIONS: The prevalence
      of metronidazole-resistant H. pylori strains remained static whilst the
      prevalence of clarithromycin-resistant strains was not rare in Hong Kong. An
      alarming 7.2% of patients were resistant to both the antimicrobials, which had a
      definite impact on treatment success. All cases of resistance to clarithromycin
      were due to A2144G mutation in 23S rRNA of H. pylori.

PMID- 10886047
TI  - Managing heartburn at the 'base' of the GERD 'iceberg': effervescent ranitidine
      150 mg b.d. provides faster and better heartburn relief than antacids.
AB  - BACKGROUND: Many individuals with heartburn self-medicate with antacids for
      relief of their symptoms. AIM: To compare efficacy of effervescent ranitidine to
      as-needed calcium carbonate antacids in subjects who self-treat heartburn.
      METHODS: A total of 155 subjects with frequent antacid-responsive heartburn were
      randomized to receive effervescent ranitidine 150 mg tablets b.d., or as-needed
      calcium carbonate 750 mg for 12 weeks. Endoscopic oesophagitis severity and
      mucosal histology were assessed at baseline, and at weeks 6 and 12. Heartburn
      frequency, severity, and antacid consumption were recorded daily, and quality of
      life was assessed at baseline, and at weeks 6 and 12. RESULTS: Heartburn
      frequency and severity were significantly decreased after 1 day of ranitidine (P
      < 0.02). By week 6, ranitidine had significantly decreased rescue antacid
      consumption (7.3 tablets, P < 0.001) vs. antacids (14.1 tablets). Endoscopic
      oesophagitis healing (</= grade 1) was significantly better with ranitidine (55%,
      P=0.022) vs. antacids (29%). Quality of life was improved by both treatments;
      however, ranitidine was numerically superior for all quality of life parameters,
      statistically superior for several quality of life indices at week 6 and for the
      pain-related index by week 12 (P < 0. 05). CONCLUSIONS: For subjects self
      administering antacids for chronic heartburn, effervescent ranitidine 150 mg b.d.
      is more effective than antacids in reducing heartburn, healing erosive
      oesophagitis, alleviating pain, and improving quality of life.

PMID- 10886048
TI  - Efficacy of sucralfate for Helicobacter pylori eradication triple therapy in
      comparison with a lansoprazole-based regimen.
AB  - BACKGROUND: Sucralfate has an inhibitory action against Helicobacter pylori and
      enhances the anti-H. pylori activity of antimicrobials. AIM: To evaluate the
      efficacy and safety of sucralfate-based eradication therapy for H. pylori
      infection, compared with that based on lansoprazole, in a randomized multicentre
      study. SUBJECTS AND METHODS: The subjects were 150 H. pylori-positive patients.
      They were randomly assigned to one of two regimens for 2 weeks: sucralfate 1 g
      t.d.s., amoxycillin 500 mg t.d.s., and clarithromycin 400 mg b.d. (SAC regimen:
      75 patients); or lansoprazole 30 mg o.m. with the same antimicrobial medications
      (LAC regimen: 75 patients). Cure of infection was assessed by a 13C urea breath
      test 1 month after completion of treatment. RESULTS: Eight patients (four in the
      SAC group and four in LAC group) could not continue therapy because of severe
      diarrhoea, and three did not take the 13C urea breath test after therapy. Cure
      rates for intention-to-treat, all-patients-treated, and per protocol analysis in
      the SAC group were 80%, 83%, and 88%, respectively, and those in the LAC group
      were 87%, 87%, and 92%, respectively. There were no significant differences in
      cure rate or adverse effects between the two regimens. CONCLUSION: Sucralfate in
      combination with amoxycillin and clarithromycin is as effective as lansoprazole
      based eradication therapy for H. pylori.

PMID- 10886049
TI  - Cerebral near infrared spectroscopy for the measurement of indocyanine green
      elimination in cirrhosis.
AB  - BACKGROUND: Indocyanine green (ICG) clearance is a useful indicator of hepatic
      function but most measurement methods are invasive. AIM: To validate a less
      invasive technique using cerebral near infrared spectrophotometry (NIRS) to
      measure ICG elimination, and to compare it with the established methods for the
      determination of ICG clearance in a group of normal controls and patients with
      cirrhosis. METHOD: NIRS was used to measure ICG elimination in 41 cirrhotic
      patients and nine healthy volunteers. The first 13 of the cirrhotic patients also
      had their ICG clearance measured by the conventional spectrophotometric
      technique. RESULTS: NIRS ICG elimination rate (ICG-k) and spectrophotometry ICG-k
      values correlated strongly (r= 0. 828, P < 0.001, n=13). There was a significant
      reduction in the mean NIRS-k in cirrhotic patients and within Child-Pugh classes
      A, B, and C (P < 0.001). CONCLUSION: Measurement of ICG elimination by the NIRS
      method is at least as reliable as the conventional spectrophotometric technique
      in normals and in patients with cirrhosis. This technique merits further
      development for use as a bedside, less invasive liver function test.

PMID- 10886050
TI  - Effects of interferon-beta on plasma lipid and lipoprotein composition and post
      heparin lipase activities in patients with chronic hepatitis C.
AB  - BACKGROUND: Interferon therapy has been shown to induce lipid abnormalities. AIM:
      We assessed the effects of interferon-beta on the lipoprotein profile and post
      heparin lipase activities in 26 normolipaemic patients with chronic hepatitis C.
      METHODS: Interferon-beta was administered subcutaneously at doses of 6 x 106 U
      (units) three times a week, over 6 months, and lipoproteins and post-heparin
      lipases were measured at baseline and at the end of therapy. RESULTS: Plasma
      triglycerides increased by 21% due to preferential enrichment in those contained
      in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL)
      fractions. The concentration of cholesterol decreased slightly in the high
      density lipoprotein (HDL) subfractions. Lipoprotein lipase, but not hepatic
      lipase activity decreased by a 36%, and this change showed a significant negative
      correlation with changes in plasma triglycerides. Five patients (19.5%) responded
      to interferon-beta therapy. The lipoprotein profile was no different between
      responders and non-responders to therapy. CONCLUSIONS: Interferon-beta treatment
      in normolipaemic patients with chronic hepatitis C induced moderate disturbances
      in plasma lipoproteins, associated with inhibition of lipoprotein lipase
      activity.

PMID- 10886051
TI  - Effects of fedotozine on gastric emptying and upper gastrointestinal symptoms in
      diabetic gastroparesis.
AB  - BACKGROUND: Delayed gastric emptying and upper gastrointestinal symptoms occur
      frequently in patients with diabetes mellitus. AIM: To evaluate the effects of
      fedotozine on gastric emptying and gastrointestinal symptoms in diabetic
      gastroparesis. METHODS: Thirty-one diabetic patients (20 type 1, 11 type 2) with
      gastroparesis were randomized to receive fedotozine (30 mg as the tartrate) or
      placebo t.d.s. Measurements of gastric emptying (100 g ground beef labelled with
      20 MBq 99mTc-sulphur colloid chicken liver and 150 mL 10% dextrose labelled with
      10 MBq 113mIn-DTPA) and gastrointestinal symptoms were performed before and after
      12-16 days of treatment. Data are the mean +/- s.d. RESULTS: Of the 31 patients
      enrolled, two were excluded from analysis. Data from the remaining 29 patients
      (18 type 1, 11 type 2; 22 female, seven male), aged 42.7 +/- 11.1 years (of whom
      14 were randomized to fedotozine and 15 to placebo), were analysed. Fedotozine
      had no effect on either gastric emptying (solid retention at 100 min; fedotozine:
      baseline, 84 +/- 15%; treatment, 73 +/- 23% vs. placebo: baseline, 83 +/- 10%;
      treatment, 70 +/- 20%) or liquid 50% emptying time (fedotozine: baseline, 59 +/-
      32 min; treatment, 58 +/- 38 min vs. placebo: baseline, 44 +/- 9 min; treatment,
      43 +/- 21 min) or gastrointestinal symptoms (fedotozine: baseline, 4.4 +/- 2.9;
      treatment, 4.1 +/- 3.9 vs. placebo: baseline, 4.9 +/- 4.2; treatment, 4.8 +/-
      3.9). CONCLUSIONS: Fedotozine has no effect on gastric emptying in patients with
      diabetic gastroparesis.

PMID- 10886052
TI  - Regulation of nitric oxide production in cultured human T84 intestinal epithelial
      cells by nuclear factor-kappa B-dependent induction of inducible nitric oxide
      synthase after exposure to bacterial endotoxin.
AB  - BACKGROUND: Intestinal epithelium is consistently in contact with
      lipopolysaccharide (LPS) produced by intraluminal microbes. LPS induces nitric
      oxide production in many rodent cells, but in human cells it is very differently
      regulated. AIM: To test the hypothesis that exposure to LPS up-regulates nitric
      oxide synthesis in human intestinal epithelium. METHODS AND RESULTS: LPS induced
      nitric oxide synthesis in T84 cells in a time- and dose-dependent manner whereas
      detectable amounts of peroxynitrite were not produced. A novel selective
      inducible nitric oxide synthase (iNOS) inhibitor 1400 W potently inhibited LPS
      induced nitric oxide synthesis in T84 cells while dexamethasone was relatively
      ineffective. Nitric oxide production was sensitive to cycloheximide, indicating
      that it was dependent on de novo protein synthesis. Nuclear factor-kappa B (NF
      kappa B) inhibitor pyrrolidinedithiocarbamate abolished iNOS and nitric oxide
      production. Nitric oxide synthesis was also suppressed by genistein (tyrosine
      kinase inhibitor) and PD 98059 (p44/42 MAP kinase inhibitor) but enhanced by SB
      203580 (p38 MAP kinase inhibitor). CONCLUSIONS: Intestinal epithelial cells
      express iNOS and produce nitric oxide in a nuclear factor-kappa B-dependent
      manner when exposed to LPS. The process is regulated by tyrosine kinases, and
      p44/42 and p38 MAP kinases. Because nitric oxide acts as an antimicrobial agent
      and immune modulator, these findings are implicated in the regulation of gut
      mucosal immunity.

PMID- 10886053
TI  - Motilides accelerate regional gastrointestinal transit in the dog.
AB  - BACKGROUND: Motilides have prokinetic effects on the upper gut during fasting,
      increasing the strength of antral contractions and stimulating gastroduodenal
      phase 3 sequences. Effects on the distal gut, and postprandially, are less well
      documented. AIM: To evaluate dose-response effects of motilin and erythromycin on
      gastric emptying, small bowel and colonic transit in the dog using a validated
      scintigraphic technique. METHODS: For gastric emptying and small bowel transit,
      99mTc labelled beads were added to a meal of dog chow (450 kcal). Regional
      colonic transit was measured by 111In labelled beads placed in a capsule which
      dissolved and released radiation into the proximal colon. Scintiscans were taken
      at regular intervals and indices of whole-gut transit were calculated. Drugs were
      given by slow intravenous administration. RESULTS: In the doses used, motilin
      accelerated regional colonic transit but did not hasten gastric emptying or small
      bowel transit. Single or repeated doses of motilin had similar effects on colonic
      transit. Erythromycin accelerated gastric emptying, small bowel transit and
      regional colonic transit. CONCLUSIONS: Motilin receptors are apparently present
      in the canine small bowel and colon. Postprandially, motilides accelerate transit
      in the distal gut.

PMID- 10886054
TI  - Helicobacter pylori eradication increases nocturnal acid breakthrough.

PMID- 10886055
TI  - The history of continuous-flow blood pumps.

PMID- 10886056
TI  - The odyssey of the artificial heart.

PMID- 10886057
TI  - Development of rotary blood pump technology: past, present, and future.
AB  - Even though clinical acceptance of a nonpulsatile blood flow was demonstrated
      almost 45 years ago, the development of a nonpulsatile blood pump was completely
      ignored until 20 years ago. In 1979, the first author's group demonstrated that
      completely pulseless animals did not exhibit any abnormal physiology if 20%
      higher blood flows were provided to them. However, during the next 10 years (1979
      1988), minimum efforts were provided for the development of a nonpulsatile,
      permanently implantable cardiac prosthesis. In 1989, the first author and his
      team at Baylor College of Medicine initiated a developmental strategy of various
      types of nonpulsatile rotary blood pumps, including a 2-day rotary blood pump for
      cardiopulmonary bypass application, a 2 week pump for ECMO and short-term
      circulatory assistance, a 2 year pump as a bridge to transplantation, and a
      permanently implantable cardiac prosthesis. Following the design and
      developmental strategy established in 1989, successful development of a 2-day
      pump (the Nikkiso-Fairway cardiopulmonary bypass pump) in 4 years (1989-1993), a
      2 week pump (Kyocera gyro G1E3 pump) in 6 years (1992-1998), and a bridge to
      transplant pump (DeBakey LVAD-an axial flow blood pump) in 10 years (1988-1998)
      was made. Currently, a permanently implantable centrifugal blood pump development
      program is successfully completing its initial Phase 1 program of 5 years (1995
      2000). Implantation exceeded 9 months without any negative findings. An
      additional 5 year Phase II program (2000-2005) is expected to complete such a
      device that will be clinically available.

PMID- 10886058
TI  - Morbidity and outcome after mechanical ventricular support using Thoratec,
      Novacor, and HeartMate for bridging to heart transplantation.
AB  - Between September 1989 and June 1999, 228 patients were supported with a
      ventricular assist device as a bridge to heart transplantation. In this study,
      the results of implantation were evaluated in patients supported with one type of
      device, including 85 supported with a Thoratec, 61 with a Novacor, and 37 with a
      HeartMate. The mean support time was 49, 148, and 124 days, respectively.
      Successful transplantation and weaning rates were 64. 7% with Thoratec, 59.0%
      with Novacor, and 62.0% with HeartMate. Cerebral embolism and drive-line and
      pocket infection were major causes of postoperative morbidity and mortality. We
      recommended that a Thoratec system be employed as a bridge to heart
      transplantation for patients with biventricular heart failure, and that a Novacor
      or HeartMate system be implanted in patients requiring a long-term circulatory
      support.

PMID- 10886059
TI  - Resuscitation and circulatory support using extracorporeal membrane oxygenation
      for fulminant pulmonary embolism.
AB  - Fulminant pulmonary embolism (PE) with circulatory collapse is associated with a
      high mortality rate due to acute right ventricular failure and hypoxia. Immediate
      and appropriate resuscitation and circulatory support in the perioperative period
      is mandatory to prevent sudden death. Extracorporeal membrane oxygenation (ECMO)
      was recently introduced for extracorporeal life support in patients with
      circulatory collapse and has provided an excellent outcome. We report on the
      effectiveness of ECMO support for fulminant PE. Seven patients were placed on
      veno-arterial ECMO for circulatory collapse caused by fulminant PE refractory to
      conventional treatment. After resuscitation, all patients underwent pulmonary
      angiography, and thrombolytic therapy was administered in all 7 patients under
      ECMO support. Three patients who did not improve by thrombolysis underwent
      embolectomy with standard cardiopulmonary bypass. Two thrombolysis and 2 surgery
      patients were weaned from bypass and survived. The duration of support ranged
      from 18-168 h (mean = 67.8 +/- 67.1 h), with maximum bypass flow rates of 2.0-4.5
      (mean = 3.5 +/- 0.9). There were no device-related complications during support.
      In total, 4 patients (57%) were successfully weaned from support and discharged
      from the hospital in good condition. All patients who survived required prolonged
      support (27, 82, 151, and 168 h). We conclude that resuscitation and circulatory
      support using ECMO can be effective, life-saving measures in cases of circulatory
      collapse caused by fulminant PE.

PMID- 10886060
TI  - Centrifugal pumps and heparin-coated circuits in surgical treatment of giant
      cerebral aneurysms.
AB  - Giant cerebral aneurysms may be untreatable by conventional neurosurgical
      techniques. Early attempts to use circulatory assistance and deep hypothermia
      were abandoned due to hemorrhagic complications. More recently, interest in
      circulatory support for complex neurosurgical procedures has been renewed. A
      consecutive series of 8 patients were operated on for giant cerebral aneurysms
      with the combined use of deep hypothermia. The protocol included careful
      preoperative cardiovascular assessment, perfect intraoperative synergy between
      neurosurgical and cardiac teams, minimally invasive peripheral vascular access
      including two femoral vein (21 F) and single arterial (17 F) femoral cannulation,
      use of total Carmeda coating on BioMedicus pumps in closed circuits, and reduced
      heparinization without Protamine reversal. All cerebral aneurysms were
      successfully treated through deep hypothermia (15-18 degrees C) as assessed by
      intraoperative fluoroscopic controls and Doppler vascular assessment. Mean
      circulatory support time was 174.2 +/- 29.6 min. Circulatory arrest period was 20
      +/- 12 min. All patients survived and were extubated within 48 h. No major
      deficit was observed clinically or on postoperative CT scan. No hemorrhagic
      complications occurred (mean transfusions was 2.2 blood units). This work
      supports an extensive use of heparin-coated surfaces for complex circulatory
      assist techniques, either for cardiac or extra cardiac complex procedures.

PMID- 10886061
TI  - Jostra Rota Flow RF-30 pump system: a new centrifugal blood pump for
      cardiopulmonary bypass.
AB  - The Rota Flow pump is a fully integrated centrifugal pump system in the Jostra
      heart-lung machine HL-20 with features such as a less friction mono-pivot bearing
      system, sealless pump housing, and spiral housing. To evaluate its
      biocompatibility, antithrombogenesity, and hemolysis, we used it as a main pump
      of cardiopulmonary bypass (CPB) in coronary artery bypass grafting (CABG) cases
      and compared it with the BioMedicus pump. From February 1999 to May 1999, 30
      consecutive patients underwent CABG under conventional CPB. Fifteen cases were
      supported by the Rota Flow RF-32 (Group R), and the remaining 15 were pumped by
      the BioMedicus BP-80 (Group B). In both groups, the flow rate was controlled in
      an equivalent value. Blood sampling was as follows: preoperative, 60 min after,
      postoperative Days (POD) 0, 1, and 2. We evaluated the plasma free hemoglobin
      (fHb) as the hemolysis parameter, beta-thromboglobulin (beta-TG) and platelet
      factor IV (PF-4) as the platelet deterioration index, C3, C4, and CH50 as
      complement activation, coagulation function, fibrinolytic factor and
      thrombomodulin, nitric oxide (NO), and endothelin as endothelial deterioration.
      This system was very easily and simply controlled and had excellent response.
      Perioperative laboratory data were not markedly changed in either group. The Rota
      Flow demonstrated equivalent value of biocompatibility and hemolysis as compared
      with the BioMedicus BP-80, which is a standard centrifugal pump. After pumping,
      no thrombus formation or pivot wear was observed inside the pump. This
      atraumatic, small centrifugal pump is suitable not only for CPB but also for long
      term circulatory support.

PMID- 10886062
TI  - Closed circuit cardiopulmonary bypass with centrifugal pump for open-heart
      surgery: new trial for air removal.
AB  - The purpose of this study is to examine the efficiency of venous air removal with
      a new cardiopulmonary bypass (CPB) circuit design for conventional open-heart
      surgeries. A main concern with a closed circuit for open-heart surgeries is air
      entrainment into the venous line. A venous filter was placed proximal to the
      centrifugal pump. The circuit proximal to the centrifugal pump was divided into
      two lines; one line was attached to the venous reservoir outlet. By clamping the
      line to the reservoir, this circuit becomes closed. Negative pressure was applied
      to the purge line connected to the venous reservoir for venous air removal. Micro
      bubbles were measured at two locations, both distal to the venous and arterial
      filters. When the injection rate reached 100 ml/min, with the air-injection over
      30 s, micro bubbles greater than 40 micro were observed at the outlet of venous
      filter. However, there was no micro bubble greater than 40 micro detected at the
      outlet of arterial filter. Although micro bubbles greater than 40 micro were not
      detected at the outlet of the arterial filter up to the injection rate of 300
      ml/min, when the injection rate reached 400 ml/min, micro bubbles greater than 50
      microm were detected distal to the arterial filter. From this examination, we
      determined that air entrained in the venous line up to approximately 300 ml/min
      is automatically removed by this method with the pressure-balanced condition.
      This pressure balance means that resistance of venous return, gravity siphon,
      negative pressure by centrifugal pump, and negative pressure applied to the air
      purge line of the filter are balanced; that is, the venous return is sufficient,
      and the venous reservoir volume is kept stable. From this study we determined
      that this circuit design efficiently removes the entrained air in the venous
      line.

PMID- 10886063
TI  - Particles released from the Gyro C1E3 during simulated extracorporeal
      circulation.
AB  - Evaluation of released particles from the blood pump during extracorporeal
      circulation is an important aspect because the particles may cause microembolism.
      The Gyro C1E3 is a centrifugal blood pump that has an impeller suspended by
      double pivot bearings inside the housing; therefore, it is important to evaluate
      the released particles. The C1E3 was driven for 14 days to simulate clinical left
      ventricular assist device (LVAD) and percutaneous cardiopulmonary support (PCPS).
      Also, a roller pump was driven for 2 days as a comparison. Released particles
      were weighed and examined by SEM. After 14 days of pumping, the particles from
      the C1E3 were 238.6 microg in an LVAD condition. The particles with the roller
      pump were 270.2 microg after only 2 days. Average particle sizes with the roller
      pump and C1E3 were 3.7 and 0.6 microm, respectively. These results suggest that
      the Gyro C1E3 substantially reduces the risk of microembolism from released
      particles.

PMID- 10886064
TI  - Vacuum assisted cardiopulmonary bypass in minimally invasive cardiac surgery: its
      feasibility and effects on hemolysis.
AB  - The present study describes a cardiopulmonary bypass (CPB) technique that
      incorporates vacuum assisted venous drainage and arterial return using a
      centrifugal pump in minimally invasive cardiac surgery (MICS). The technique was
      performed on 40 patients scheduled to undergo MICS. The proposed CPB technique
      enables a good operative field to be obtained even through a limited incision
      through the use of peripheral cannulation using small cannulae. Vacuum pressure
      was applied to the venous reservoir (-43 +/- 14 mm Hg) to maintain adequate CPB
      flow (>2.4 L x min-1 x M-2). The effects of CPB on hemolysis were subsequently
      compared between patients who underwent the proposed procedure (MICS group; n =
      6) and a control group who underwent coronary arterial bypass grafting (CABG
      group; n = 6) with conventional CPB. Plasma free hemoglobin (FHb) increased and
      plasma haptoglobin (Hp) decreased during CPB in both groups, with no significant
      difference between the groups. By the next day, FHb had returned to pre-CPB
      levels whereas Hp remained lower in both groups. Again, these values did not
      differ significantly between groups. Thus, we conclude that the proposed CPB
      technique is useful in MICS with acceptable effects on hemolysis.

PMID- 10886065
TI  - Development of a completely closed circuit using an air filter in a drainage
      circuit for minimally invasive cardiac surgery.
AB  - The completely closed circuit system is the future direction of cardiopulmonary
      bypass because of its compactness and superior biocompatibility. The most serious
      obstacle for clinical application is the sucking of air bubbles into the drainage
      circuit. The purpose of this study was to remove the air bubbles from the
      drainage circuit. Infusing 50 ml/min of air bubbles into the drainage circuit of
      the usual closed circuit, and infusing 50, 100, and 150 ml/min of air into the
      drainage circuit of a newly developed closed circuit (drainage circuit using an
      air filter), the number and size of air bubbles were observed at the outlet of
      the arterial filter. In the usual closed circuit, many air bubbles of over 40
      microm were detected within 5 s at a blood flow of 4 L/min because the
      centrifugal pump decreased the size of the bubbles, which then passed through the
      oxygenator and arterial filter. Air bubbles of over 40 micro were not detected in
      the newly developed closed circuit within 5 min at a blood flow of 4 L/min. The
      removal of air mixed into the completely closed circuit was possible with a
      drainage circuit using an air filter that was developed. The clinical use of the
      completely closed circuit for minimally invasive cardiac surgery (MICS) became
      possible based on this development.

PMID- 10886066
TI  - Development of the NEDO implantable ventricular assist device with Gyro
      centrifugal pump.
AB  - The Gyro centrifugal pump, PI (permanently implantable) series, is being
      developed as a totally implantable artificial heart. Our final goal is to
      establish a "functional TAH," a totally implantable biventricular assist system
      (BiVAS) with centrifugal pumps. A plastic prototype pump, Gyro PI 601, was
      evaluated through in vitro and in vivo studies as a single ventricular assist
      device (VAD). Based upon these results, the pump head material was converted to a
      titanium alloy, and the actuator was modified. These titanium Gyro pumps, PI 700
      series, also were subjected to in vitro and in vivo studies. The Gyro PI 601 and
      PI 700 series have the same inner dimensions and characteristics, such as the
      eccentric inlet port, double pivot bearing system, secondary vane, and magnet
      coupling system; however, the material of the PI 700 is different from the PI
      601. The Gyro PI series is driven by the Vienna DC brushless motor actuator. The
      inlet cannula of the right ventricular assist system (RVAS) specially made for
      this system consists of 2 parts: a hat-shaped silicone tip biolized with gelatin
      and an angled wire reinforced tube made of polyvinylchloride. The pump-actuator
      package was implanted into 8 calves in the preperitoneal space, bypassing from
      the left ventricle apex to the descending aorta for the left ventricular assist
      system (LVAS) and bypassing the right ventricle to the main pulmonary artery for
      the RVAS. According to the PI 601 feasibility protocol, 2 LVAS cases were
      terminated after 2 weeks, and 1 LVAS case and 1 RVAS were terminated after 1
      month. The PI 700 series was implanted into 4 cases: 3 LVAS cases survived for a
      long term, 2 of them over 200 days (72-283 days), and 1 RVAS case survived for 1
      month and was terminated according to the protocol for a short-term
      antithrombogenic screening and system feasibility study. Regarding power
      consumption, the plastic pump cases demonstrated from 6.2 to 12.1 W as LVAS and
      7.3 W as RVAS, the titanium pump cases showed from 10.4 to 14.2 W as LVAS and
      15.8 W as RVAS. All cases exhibited low hemolysis. The renal function and the
      liver function were maintained normally in all cases throughout these
      experimental periods. In the 2 RVAS cases, pulmonary function was normally
      maintained. No calves demonstrated thromboembolic signs or symptoms throughout
      the experiments except Case 1 with the plastic pump. However, in the plastic pump
      cases, bilateral renal infarction was suspected in 2 cases during necropsy
      whereas no abnormal findings were revealed in the titanium pump cases. There were
      also no blood clots inside the PI 700 series. As for the 601, the explanted pumps
      demonstrated slight thrombus formations at the top and bottom pivots except in 1
      case. The Gyro PI series, especially the PI 700 series, demonstrated superior
      performance, biocompatibility, antithrombogenicity and low hemolysis. Also, the
      durability of the actuator was demonstrated. Based on these results, this
      titanium centrifugal pump is suitable as an implantable LVAS and RVAS. It is
      likely that the Gyro PI series is a feasible component of the BiVAS functional
      TAH.

PMID- 10886067
TI  - Magnetically suspended rotary blood pump with radial type combined motor-bearing.
AB  - A magnetically suspended centrifugal blood pump is being developed with a
      combined motor-bearing for long-term ventricular assist systems. The combined
      motor-bearing actively suspends a rotor in a radial direction to deal with radial
      force unbalance in the pump and rotates the rotor by using the electric magnetic
      field. Therefore, the pump has no mechanical parts such as bearings of the motor
      and has a long lifetime. The developed pump consists of a thin rotor with a semi
      open-type 6 vane impeller and a stator to suspend and rotate the rotor. The rotor
      has 4-pole permanent magnets on the circumferential surface. The outer diameter
      and the thickness of the rotor are 60 mm and 8 mm, respectively. Axial movement
      and tilt of the rotor are restricted by passive stability based on the thin rotor
      structure. Radial movements of the rotor, such as levitation in radial direction
      and rotation, are controlled actively by using electric magnets of the stator.
      The electric magnet coils to produce levitation and rotation forces are
      constructed on the periphery stator. The p +/- 2-pole algorithm and the
      synchronous motor mechanism are adopted to levitate and rotate the rotor. The
      radial gap between the rotor and the stator is 1 mm. A closed-loop circuit filled
      with water was connected to the developed pump to examine the basic performance
      of the pump and the magnetic suspension system. Maximum rotational speed, flow
      rate, and head were 2,800 rpm, 11 L/min, and 270 mm Hg, respectively. The rotor
      with the impeller could be suspended completely during the entire pumping
      process. We conclude the pump with the combined motor-bearing has sufficient
      performance for the blood pump.

PMID- 10886068
TI  - VentrAssist hydrodynamically suspended, open, centrifugal blood pump.
AB  - A novel design is presented for an implantable centrifugal blood pump in which
      hydrodynamic forces acting on tapered edges of thick blades are used to suspend
      the impeller. The pump has no shaft, seals, or "spiders" and has clean flow lines
      with no stagnant zones. At 5 L/min and 100 mm Hg differential pressure, the
      measured hemolysis was in the range NIH 0.002-.005 g/100 L and the system
      efficiency was 19%.

PMID- 10886069
TI  - Paradoxical effects of viscosity on the VentrAssist rotary blood pump.
AB  - The ability of the VentrAssist blood pump to perform at its optimum design point
      is determined by a number of factors such as geometry of the pump, surface
      roughness, and fluid properties. Once the fluid properties are known, the
      performance characteristics of the pump can be optimized for that fluid. It is
      important to understand the effects of dynamic viscosity mu (called simply
      viscosity hereafter) on the performance characteristics and stability of the
      pump. The performance envelope of the pump and the needs of the patient must be
      matched. The VentrAssist pump has no shaft, seals, or fixed bearings and relies
      on the fluid-dynamic forces to maintain its effective performance. A number of
      different fluids have been tested to determine the effects of viscosity and
      density on pump performance. These include aqueous glycerol, red blood cells
      (RBCs) suspended in phosphate buffered saline solution (PBS), and Haemaccel. The
      effects of viscosity on the bearing stiffness, stage efficiency, and the pressure
      flow rate (HQ) are characterized. The experimental results show a slight increase
      in the pressure rise across the pump shown as a positive upward shift of the H-Q
      curves with a decrease in viscosity; however, this is relatively small. A paradox
      in system efficiency exists: for a given fluid asymptotic viscosity, the system
      efficiency (product of magnetic and stage efficiency) using Haemaccel or PBS is
      greater than for the same viscosity of aqueous glycerol.

PMID- 10886070
TI  - Fluid dynamic characteristics of the VentrAssist rotary blood pump.
AB  - The VentrAssist pump has no shaft or seal, and the device is unique in design
      because the rotor is suspended passively by hydrodynamic forces, and urging is
      accomplished by an integrated direct current motor rotor that also acts as the
      pump impeller. This device has led to many challenges in its fluidic design,
      namely large flow-blockage from impeller blades, low stiffness of bearings with
      concomitant impeller displacement under pulsatile load conditions, and very small
      running clearances. Low specific speed and radial blade off-flow were selected in
      order to minimize the hemolysis. Pulsatile and steady-flow tests show the
      impeller is stable under normal operating conditions. Computational fluid
      dynamics (CFD) has been used to optimize flow paths and reduce net axial force
      imbalance to acceptably small values. The latest design of the pump achieved a
      system efficiency of 18% (in 30% hematocrit of red blood cells suspended in
      phosphate-buffered saline), and efficiency was optimized over the range of
      operating conditions. Parameters critical to improving pump efficiency were
      investigated.

PMID- 10886071
TI  - Computational fluid dynamics analysis of hydrodynamic bearings of the VentrAssist
      rotary blood pump.
AB  - The computational fluid dynamics (CFD) package CFX-TASCflow was applied to
      simulate the flows through the blood pump hydrodynamic bearings. The three
      dimensional flow patterns through the bearings were predicted and the hydraulic
      performance analyzed. The computations were carried out at 3 axial positions of
      the pump impeller. Net lift force away from the nearer part of the housing
      increased when the impeller moved closer to this part. Radial force and drag
      force were also found. Separated flows were observed at the leading and trailing
      edge of the bearing gap. To test the CFD package, a series of two-dimensional
      computations were also carried out for various bearing geometries. The results
      were compared with published experimental data.

PMID- 10886072
TI  - Numerical analysis of blood flow in the clearance regions of a continuous flow
      artificial heart pump.
AB  - The CFVAD3 is the third prototype of a continuous flow ventricular assist device
      being developed for implantation in humans. The pump consists of a fully shrouded
      4-blade impeller supported by magnetic bearings. On either side of this suspended
      rotating impeller is a small clearance region through which the blood flows. The
      spacing and geometry of these clearance regions are very important to the
      successful operation of this blood pump. Computational fluid dynamics (CFD)
      solutions for this flow were obtained using TascFlow, a software package
      available from AEA Technology, U.K. Flow in these clearance regions was studied
      parametrically by varying the size of the clearance, the blood flow rate into the
      pump, and the rotational speed of the pump. The numerical solutions yield the
      direction and magnitude of the flow and the dynamic pressure. Experimentally
      measured pump flow rates are compared to the numerical study. The results of the
      study provide guidance for improving pump efficiency. It is determined that
      current clearances can be significantly reduced to improve pump efficiency
      without negative impacts.

PMID- 10886073
TI  - Development of a compact, sealless, tripod supported, magnetically driven
      centrifugal blood pump.
AB  - In this study, a tripod supported sealless centrifugal blood pump was designed
      and fabricated for implantable application using a specially designed DC
      brushless motor. The tripod structure consists of 3 ceramic balls mounted at the
      bottom surface of the impeller moving in a polyethylene groove incorporated at
      the bottom pump casing. The follower magnet inside the impeller is coupled to the
      driver magnet of the motor outside the bottom pump casing, thus allowing the
      impeller to slide-rotate in the polyethylene groove as the motor turns. The pump
      driver has a weight of 230 g and a diameter of 60 mm. The acrylic pump housing
      has a weight of 220 g with the priming volume of 25 ml. At the pump rpm of 1,000
      to 2,200, the generated head pressure ranged from 30 to 150 mm Hg with the
      maximum system efficiency being 12%. When the prototype pump was used in the
      pulsatile mock loop to assist the ventricle from its apex to the aorta, a strong
      correlation was obtained between the motor current and bypass flow waveforms. The
      waveform deformation index (WDI), defined as the ratio of the fundamental to the
      higher order harmonics of the motor current power spectral density, was computed
      to possibly detect the suction occurring inside the ventricle due to the
      prototype centrifugal pump. When the WDI was kept under the value of 0.20 by
      adjusting the motor rpm, it was successful in suppressing the suction due to the
      centrifugal pump in the ventricle. The prototype sealless, centrifugal pump
      together with the control method based on the motor current waveform analysis may
      offer an intermediate support of the failing left or right ventricle bridging to
      heart transplantation.

PMID- 10886074
TI  - Acronyms, abbreviations and initialisms.

PMID- 10886075
TI  - A novel basic protein from human kidney which inhibits calcium oxalate crystal
      growth.
AB  - OBJECTIVES: To isolate calcium oxalate-binding proteins from human kidney and
      characterize the functional properties. MATERIALS AND METHODS: Calcium oxalate
      crystals were prepared and allowed to interact at two different pH values with
      Triton-extracted human kidney homogenate. The proteins in the homogenate were
      isolated and fractionated on a cellulose column, and purified by high-performance
      liquid chromatography. The protein with the greatest oxalate binding activity at
      pH 4.5 was analysed for its amino-acid composition and characterized by Scatchard
      plot analysis, crystal growth, nucleation and aggregation studies. RESULTS: Three
      major protein fractions were eluted when calcium oxalate monohydrate was adsorbed
      at both pH values (designated as fractions I-III, according to their order of
      elution). The yield of fraction I and III was increased when adsorbed at an
      acidic pH. However, only fraction III had maximum oxalate binding activity at pH
      4.5. When purified, this protein had maximum oxalate binding activity of
      approximately 270 pmol/mg protein and a molecular weight of approximately 23 kDa.
      Amino acid analysis showed that 18% of the total molar proportion was of basic
      amino acids, e.g. lysine and arginine, while acidic amino acids accounted for
      only 11%. Both alanine and glycine constituted approximately 41% of the total
      molar proportion. Modifications to the lysine group abolished oxalate-binding
      activity of the protein. The protein inhibited crystal growth by 82% at 0.8
      micromol/L, while it inhibited the nucleation and aggregation of the crystals by
      6% and 28%, respectively, at 49 nmol/L. The inhibition of both nucleation and
      aggregation was higher at pH 5.7 than at pH 7.4. Significantly, the protein
      induced the formation of intertwined calcium oxalate dihydrate crystals in a
      medium known to induce the formation of individual dihydrate crystals.
      CONCLUSION: The protein described here is the first reported basic inhibitor of
      calcium oxalate crystal growth with oxalate-binding activity at pH 4.5 that
      modulates calcium oxalate crystallization. It is suggested that this protein may
      play a physiologically significant role in inhibiting stone formation in acidic
      urine.

PMID- 10886076
TI  - Prognostic significance of p27Kip1 and Ki-67 expression in carcinoma of the renal
      pelvis and ureter.
AB  - OBJECTIVE: To determine the significance of p27(Kip1) (p27) for tumour behaviour
      and prognosis of patients with transitional cell carcinoma (TCC) of the renal
      pelvis and ureter. PATIENTS AND METHODS: Using immunohistochemical staining, the
      relationship was evaluated between p27 protein level (low < 50%, high > 50%) and
      the Ki-67 labelling index (low < 30%, high > 30%) and clinicopathological
      features of 37 consecutive Japanese patients with TCC of the renal pelvis and
      ureter. RESULTS: Low levels of p27 correlated with higher tumour stage (P < 0.05)
      and positive lymph node metastases (P < 0.05). There was no significant
      association between p27 staining and the grade and tumour proliferation as
      assessed by the Ki-67 index. A high Ki-67 index correlated with higher grade and
      stage (P < 0.05). Kaplan-Meier plots of survival rate in patients with low or
      high p27 staining showed that low levels correlated with a shorter disease-free
      and overall survival (P < 0.001 and P < 0.01, respectively). Similarly, patients
      with a high Ki-67 index had lower disease-free and overall survival than those
      with a low Ki-67 index (P < 0.01 and P < 0.05, respectively). The Cox
      proportional hazards model showed that a low level of p27 was an independent
      predictor of a shorter disease-free (P < 0.01) and overall survival (P < 0.05) on
      univariate analysis, but not of overall survival on multivariate analysis. A high
      Ki-67 index was an independent prognostic marker for shorter disease-free
      survival on univariate and multivariate analysis (P < 0.01) and for overall
      survival on multivariate analysis (P < 0.05). In those with a high Ki-67 index,
      increased p27 staining was associated with a better prognosis than decreased
      staining for disease-free and overall survival (log-rank test, P < 0. 01 and P <
      0.05, respectively). CONCLUSIONS: The finding that a low level of p27 is
      associated with tumour invasion and unfavourable prognosis indicates that p27 may
      be a useful prognostic marker for survival in upper urinary tract cancer.

PMID- 10886077
TI  - Risk factors for adult renal cell carcinoma: a systematic review and implications
      for prevention.

PMID- 10886078
TI  - Renal transplantation in patients with an augmentation cystoplasty.
AB  - OBJECTIVE: To retrospectively review our experience over a 10-year period of
      renal transplantation in patients with augmented bladders and thus assess the
      safety of this procedure. PATIENTS AND METHODS: Ten transplant recipients who had
      previously undergone augmentation cystoplasty were reviewed; a cadaveric kidney
      was transplant in each case. The donor ureter was anastomosed to the augment
      bladder in six patients, in three to the native ureter and in one the donor renal
      pelvis was anastomosed to the native ureter. RESULTS: No patients died and nine
      of the 10 grafts were functioning at a mean follow-up of 27 months. The mean (SD)
      serum creatinine level at the follow-up was 100.8 (27.25) mmol/L. Four patients
      had 10 episodes of urosepsis requiring hospital admission, with only one graft
      lost. CONCLUSION: Renal transplantation can be performed safely in patients with
      an augmentation cystoplasty.

PMID- 10886079
TI  - Oestrogen and progesterone receptor expression in the female lower urinary tract,
      with reference to oestrogen status.
AB  - OBJECTIVE: To assess the incidence and distribution of both oestrogen and
      progesterone receptors throughout the female lower urinary tract, and to compare
      receptor expression in women of varying oestrogen status. PATIENTS AND METHODS:
      The study included 90 women undergoing surgery for urogynaecological conditions;
      33 were premenopausal, 26 postmenopausal and taking no oestrogen supplementation,
      and 31 postmenopausal and receiving some form of hormone-replacement therapy.
      Biopsies were taken during surgery from the bladder dome, trigone, proximal
      urethra, distal urethra, vagina and vesicovaginal fascia in the region of the
      bladder neck. All biopsies were routinely fixed and processed for
      histopathological assessment, and were then labelled immunohistochemically with
      monoclonal antibodies directed against human oestrogen (NCL-ERLH2) and
      progesterone (NCL-PGR) receptors. Both oestrogen and progesterone receptor
      expression were assessed in the epithelial, subepithelial and muscle/deeper
      fascial regions of all tissue for overall tissue positivity for each receptor,
      and by semiquantitative analysis of receptor concentration using histochemical
      scoring of the tissues. RESULTS: Oestrogen receptors were consistently detected
      in the squamous epithelia and were consistently absent in the urothelial tissues
      of the lower urinary tract of all women irrespective of oestrogen status; there
      was no significant variation in histological score. Progesterone receptor
      expression was more variable, being mostly subepithelial, and significantly lower
      in postmenopausal women receiving no oestrogen replacement. CONCLUSION: These
      findings confirm the female lower urinary tract to be a target organ for the
      action of oestrogen and progesterone, and shed further light on the areas of the
      lower urinary tract likely to respond to hormone-replacement therapy. This may
      have implications for the use of oestrogen supplementation in the treatment of
      lower urinary tract disorders of postmenopausal women.

PMID- 10886080
TI  - Tension-free vaginal tape for primary genuine stress incontinence: a two-centre
      follow-up study.
AB  - OBJECTIVE: To assess the safety and efficacy of the tension-free vaginal tape
      procedure in the treatment of primary genuine stress incontinence. PATIENTS AND
      METHODS: A two-centre follow-up study was conducted on 40 women with
      urodynamically confirmed primary genuine stress incontinence who had a tension
      free vaginal tape inserted under local anaesthesia with sedation. Operative
      details were recorded and all patients followed up both subjectively, and
      objectively with repeat urodynamic studies and pad testing. RESULTS: The mean
      (range) age of the women was 51.1 (33-86) years, the median parity 2 (0-4) and
      mean body mass index 25.1 (19-35). The mean anaesthesia and operative duration
      was 42 (25-65) min; 93% of the women resumed immediate spontaneous voiding with
      no need for catheterization. The mean inpatient stay was 2.2 (2-4) days (where 2
      days is equivalent to one night in hospital). The follow-up was conducted at a
      mean interval of 12.3 (6-24) months. Subjectively, 80% of women were cured and
      17.5% significantly improved; objectively, genuine stress incontinence was cured
      in 95%. Symptomatic postoperative detrusor instability was found in 15% of women
      and symptoms of voiding dysfunction identified in 5% of women. There were no
      defects in healing or tape rejection. CONCLUSION: The tension-free vaginal tape
      procedure is a promising new technique that, in this short-term analysis, appears
      to be safe and effective. Intra-operative complications are uncommon and both
      hospital stay and recovery are short. Voiding complications are rare but
      symptomatic postoperative detrusor instability had an incidence of 15%.

PMID- 10886081
TI  - Ethanol-glycine irrigating fluid for transurethral resection of the prostate in
      practice.
AB  - OBJECTIVE: To evaluate the usefulness of a tracer of 1% ethanol in 1. 5% glycine
      in the early detection of irrigation fluid absorption during transurethral
      resection of the prostate (TURP). PATIENTS AND METHODS: Patients (120) undergoing
      TURP were irrigated with 1% ethanol in 1.5% glycine solution and their expired
      air tested for alcohol every 10 min during the procedure. RESULTS: In all, 112
      patients were assessed; over half of the patients absorbed the irrigation fluid
      and they had a significantly lower postoperative serum sodium concentration (P <
      0.002). Fourteen patients (12.5%) absorbed over 500 mL and two (1.8%) developed
      clinical features of the TUR syndrome. The experience of the surgeon, the weight
      of resected chips and the operative duration were not significantly predictive of
      absorption. CONCLUSION: A tracer amount of ethanol in the irrigant is reliable
      for detecting absorption. Irrigating fluid absorption was unpredictable, thus
      supporting the case for routine monitoring.

PMID- 10886082
TI  - Clinical efficacy of a new 30-min algorithm for transurethral microwave
      thermotherapy: initial results.
AB  - OBJECTIVE: To assess the efficacy of a new 30-min algorithm for high-energy
      transurethral microwave thermotherapy (TUMT, Prostasoft 3.5) in the treatment of
      men with lower urinary tract symptoms (LUTS) caused by benign prostatic
      hyperplasia. PATIENTS AND METHODS: A total of 108 men (mean age 66 years) with
      bothersome LUTS were treated with the new TUMT protocol. All patients were
      evaluated using a standard assessment at baseline, 6, 12, 26 and 52 weeks after
      TUMT. The evaluation included the assessment of objective and subjective outcome
      measures, with a urodynamic evaluation using pressure-flow analysis, and the
      occurrence of adverse events. RESULTS: The treatment was well tolerated. In
      general, the International Prostate Symptom Score improved from a mean of 20.0 at
      baseline to a mean of 9.3 at 6 months after treatment. The maximum urinary flow
      improved from 9.4 mL/s to 14.6 mL/s at 6 months. The mean duration of
      catheterization was 17.9 days. The urodynamic evaluation showed a change from the
      obstructed to the equivocal zone on the Abrams-Griffith nomogram. There were no
      serious complications. Urgency and frequency were the most frequent side-effects
      after treatment; these all resolved within 3 months. CONCLUSION: High-energy TUMT
      using the new high-dose Prostasoft 3.5 protocol appears to be a safe and
      effective treatment. The faster procedure improves the tolerance of the
      treatment. The subjective and objective improvements were significant and the
      treatment-related morbidity low. A longer follow-up is needed to assess the
      durability of this new treatment protocol.

PMID- 10886083
TI  - A urethral stent for the treatment of detrusor-striated sphincter dyssynergia.
AB  - OBJECTIVE: To assess the technique, efficacy and complications of the Ultraflex
      urethral stent (Boston Scientific Corp., Boston, MA) for the treatment of
      detrusor-striated sphincter dyssynergia (DSD). PATIENTS AND METHODS: Forty
      consecutive patients with DSD who had a Ultraflex stent placed in the membranous
      urethra were evaluated prospectively. DSD was caused by spinal cord injury in 30,
      multiple sclerosis in six and other neurological diseases in four. All patients
      were either tetraplegic or paraplegic and unable to use intermittent self
      catheterization. Previous bladder management consisted of an indwelling catheter
      in 15 patients, chronic suprapubic catheters in two, intermittent catheterization
      in nine, and trigger reflex micturition in 14. The Ultraflex stent was placed
      under local anaesthesia. The stents were 50 mm long in 36 patients, 45 mm in two
      and 40 mm in two. The mean (SD) follow-up was 16.9 (13. 8) months. RESULTS: The
      mean (SD) residual urine decreased from 245. 9 (117) mL before stenting to 65.2
      (19.3) mL at 12 months afterward (n = 19). One stent was removed at 13 months for
      chronic prostatic and urinary tract infection leading to autonomic dysreflexia.
      There was no stent stenosis and 17 of 18 stents had > 75% epithelial coverage at
      one year. None of the stents migrated. Seven patients underwent secondary bladder
      neck incision through the stent. The stent length was increased in four patients
      using a second overlapping distal stent, twice during the first procedure and
      twice within 6 months because the sphincter was inadequately covered.
      CONCLUSIONS: The Ultraflex stent achieved the expected results for a prosthetic
      sphincterotomy and appears to be an appropriate but less invasive treatment for
      DSD.

PMID- 10886084
TI  - Three-dimensional contrast-enhanced power Doppler ultrasonography and
      conventional examination methods: the value of diagnostic predictors of prostate
      cancer.
AB  - OBJECTIVE: To investigate the value of three-dimensional contrast-enhanced power
      Doppler ultrasonography (3D-CE-PDU) in the diagnosis of prostate cancer and to
      compare 3D-CE-PDU with digital rectal examination (DRE), prostate-specific
      antigen (PSA) levels, grey-scale ultrasonography (GSU) and PDU. PATIENTS AND
      METHODS: The study comprised 30 patients with localized prostate cancer scheduled
      to undergo radical prostatectomy and 29 with clinical BPH scheduled to undergo
      transurethral microwave thermotherapy. The 3D-CE-PDU examinations were carried
      out using 2.5 g of microbubble ultrasound contrast medium; the images were stored
      digitally to allow off-line analysis. All the reconstructed 3D images of the
      prostate were evaluated blindly in random order by two investigators (one expert
      and one novice). The images were scored according to asymmetry (0-2) and vessel
      distribution (0-3). Marked asymmetry (2) and/or a focal increase in vascularity
      (> 2) were considered as suspicious for prostate malignancy. Diagnostic
      predictions using the DRE, PSA level, GSU, PDU, 3D-CE-PDU and their combinations
      were investigated using receiver operating characteristic (ROC) curves. RESULTS:
      True-positive and true-negative rates of the 3D-CE-PDU were 87% (26/30) and 79%
      (23/29), respectively, for the expert observer. The sensitivity of 3D-CE-PDU was
      higher than that of DRE, GSU and PDU, but not PSA level, and the specificity was
      lower, again except for PSA level. However, when compared with those of the other
      modalities in single-test evaluations, 3D-CE-PDU, and a combination of 3D-CE-PDU
      and PSA level, had the largest area under the ROC curve (0. 830 and 0.933,
      respectively). The diagnostic agreement between the examiners was 76% (Cohen
      kappa statistic, 0.5). CONCLUSION: In this selected group of patients, 3D-CE-PDU
      alone was a better diagnostic tool than the DRE, PSA level, GSU or PDU alone. The
      most suitable diagnostic predictor for prostate cancer was a combination of 3D-CE
      PDU and PSA level.

PMID- 10886085
TI  - Prostatic manipulation has a minimal effect on complexed prostate-specific
      antigen levels.
AB  - OBJECTIVE: To assess the effect of prostatic manipulation on complexed prostate
      specific antigen (cPSA), as various forms of prostatic manipulation are known to
      increase the serum free and total PSA level. PATIENTS AND METHODS: A series of 92
      men (58 after prostatic biopsy, 16 after digital rectal examination and 18 after
      flexible cystoscopy) were assessed. Blood samples were taken from each patient
      before and 30 min after manipulation. Total and cPSA levels were measured using
      appropriate assays, respectively. RESULTS: There was no significant increase in
      cPSA levels after flexible cystoscopy and digital rectal examination, but
      prostate biopsy caused a statistically significant although minimal rise in cPSA
      level. There was no statistically significant increase in cPSA level after
      prostate biopsy in patients with prostate cancer (P = 0. 35) although there was a
      statistically significant but minimal rise in cPSA level in patients with benign
      histology (P < 0.01, mean increase 2.13 ng/mL) compared with that of total PSA,
      which increased markedly (P < 0.01, mean increase 19.79 ng/mL). CONCLUSION:
      Prostatic manipulation has minimal effects on cPSA levels.

PMID- 10886086
TI  - Optimizing the therapeutic approach of transurethral alprostadil.
AB  - OBJECTIVE: To investigate the efficacy and safety of two different starting doses
      of transurethral alprostadil (250 microg and 500 microg, MUSE, Vivus Inc., Menlo
      Park, CA, USA, and Astra Lakemedel AB, Sodertalje, Sweden) and the need for dose
      titration in a general population with erectile dysfunction. PATIENTS AND
      METHODS: In a 12-week randomized and open multicentre study with parallel groups,
      166 patients were randomised to a starting dose of either 250 or 500 microg of
      MUSE and evaluated for safety. Of these patients, 142 were included in the
      analysis of efficacy. MUSE marked in four doses (125, 250, 500 and 1000 microg)
      was supplied and during the trial the dose could be increased or decreased step
      wise until a satisfactory response was attained. The efficacy was assessed using
      the Erection Assessment Scale (EAS), as coitus (by diary) and the International
      Index of Erectile Function. RESULTS: The lowest dose of MUSE with which the
      patients achieved at least one EAS score of 4 or 5 was 125 microg for 1% of
      participants, 250 ++microg for 27%, 500 microg for 32%, 1000 microg for 6%, and
      finally 1000 microg plus a pubic band for 8%. Thirty-five of the 142 patients
      (25%) did not report an EAS of 4 or 5. Most patients (> 60%) achieved an EAS of 4
      or 5 on the lower doses (125, 250 and 500 microg). Almost all patients who had an
      EAS score of 4 or 5 also had intercourse. In all, 68% reported sexual intercourse
      at least once in course of the study. More patients reported penile pain while
      treated with 500 microg than with 250 microg (P < 0.05) during the first 4 weeks.
      However, the penile pain was severe in very few men and it was a minor problem.
      Hypotensive symptoms were reported six times, independently of dose level. The
      administration of MUSE was generally rated as comfortable. No patients reported
      urethral stricture, penile fibrosis, or priapism either in the clinic or at home.
      CONCLUSION: Recommending 500 microg as a starting dose increased the percentage
      of patients reporting at least one EAS of 4-5, with or without sexual
      intercourse, from 28% to 60%. No serious dose-related systemic effects were seen.
      When starting on 500 microg, patients were more likely to find directly the dose
      that gave sufficient response and treatment satisfaction. We suggest that the
      appropriate starting dose of MUSE should be 500 microg.

PMID- 10886087
TI  - Unconsummated marriage: clarification of aetiology; treatment with intracorporeal
      injection.
AB  - OBJECTIVE: To clarify the aetiological factors in unconsummated marriage in Iran,
      and to report the results of intracorporeal injection therapy for erectile
      dysfunction in these circumstances. PATIENTS AND METHODS: During a 2-year period,
      200 cases of unconsummated marriage were evaluated. A detailed history was
      obtained to clarify the circumstances of the problem; if simple measures failed
      to resolve the problem, intracorporeal injection with papaverine +/- phentolamine
      was used. RESULTS: The main factor associated with an unconsummated marriage was
      the intense social pressure to accomplish hasty coitus with an unfamiliar woman
      (some men having had no social contact with their new bride) and in the presence
      of relatives waiting nearby for evidence of the bride's virginity and
      confirmation of coitus. The initial problem was then further compounded with
      resultant erectile failure caused by anxiety about sexual performance. Inability
      to consummate the marriage was caused by premature ejaculation in 23%, erectile
      dysfunction in 61%, and a combination in 16%; 70% of patients were able to
      consummate the union after intracorporeal injection with papaverine +/-
      phentolamine. CONCLUSIONS: In addition to psychological causes and a lack of
      sexual education, the social circumstances in which partners are obliged to
      initiate and complete coitus are important factors in the aetiology of
      unconsummated marriage. Intracorporeal injection is useful in treating this
      problem and it should be the therapy of choice for unconsummated marriage in
      developing countries, where the conditions do not favour psychotherapy and where
      alternative erectogenic agents are expensive or unavailable.

PMID- 10886088
TI  - Angiogenesis and lymphangiogenesis in stage 1 germ cell tumours of the testis.
AB  - OBJECTIVE: To determine whether angiogenesis can be used as an additional
      prognostic indicator in patients with stage 1 germ cell tumours of the testis.
      PATIENTS AND METHODS: Paraffin sections were assessed immunohistochemically from
      51 patients with clinical stage 1 germ cell tumours of the testis (28 seminoma,
      23 teratoma) treated by orchidectomy and surveillance only. Sections were
      analysed for microvascular density (MVD), and expression of the angiogenic
      factors vascular endothelial growth factor (VEGF) and thymidine phosphorylase
      (TP). In addition, in the seminoma cases the presence of mRNA for the
      lymphangiogenic factor VEGF-C was examined by in situ hybridization, and its
      corresponding receptor VEGFR-3 by immunohistochemistry. RESULTS: Teratoma
      specimens had a significantly higher mean (range) MVD (85, 26-163; P < 0.01) than
      both seminoma (37, 16-91) and four normal specimens (26, 18-30). Teratoma
      specimens also had significantly higher VEGF expression than both seminoma and
      normal specimens (P < 0.01). Despite these differences between groups, and indeed
      individual tumours, there was no significant correlation between MVD and VEGF, or
      between either MVD or VEGF and relapse-free survival. TP expression was
      significantly greater in tumours than in normal specimens (P < 0.02) but with
      very little inter-tumour variation. VEGF-C mRNA and VEGFR-3 protein were detected
      in a third to a half of cases, with expression mostly around endothelial vessels.
      CONCLUSIONS: The marked differences between normal testis and tumours implicate
      angiogenesis in the biology of germ cell tumours of the testis. In addition, the
      detection of factors involved in lymphangiogenesis in some seminomas, tumours
      which initially metastasize primarily to lymph nodes, indicate that although not
      prognostic in this study, further studies are warranted in both these areas in
      the search for further prognostic indicators and therapeutic targets.

PMID- 10886089
TI  - A prospective evaluation of scrotal ultrasonography in clinical practice.
AB  - OBJECTIVES: To prospectively evaluate scrotal ultrasonography (SUS) in patients
      presenting with scrotal symptoms and to make recommendations about use of SUS in
      clinical practice. PATIENTS AND METHODS: Forty-eight men with scrotal symptoms
      were examined by a urologist and independently underwent SUS by one radiologist
      with no knowledge of the clinical diagnosis. The clinical and SUS diagnoses were
      compared and the effect on subsequent management recorded. RESULTS: The clinical
      and SUS diagnoses agreed in 35 men (73%) although SUS provided an additional
      diagnosis in half of these men. The SUS diagnosis differed in 13 men (27%)
      although the management was altered in only four patients. CONCLUSION: The
      clinical diagnosis is correct in most men with scrotal symptoms; the routine use
      of SUS is inappropriate and should be reserved for specific indications.

PMID- 10886090
TI  - Abdominal relapse in stage 1 nonseminomatous germ cell tumours of the testis
      managed by surveillance or with adjuvant chemotherapy.
AB  - OBJECTIVE: To assess the impact on patterns of recurrence of adjuvant
      chemotherapy in patients with stage 1 nonseminomatous germ cell tumours (NSGCT)
      of the testis, who have a high likelihood of relapse on surveillance if certain
      risk factors are identified in the orchidectomy specimen, and thus the
      theoretical need for retroperitoneal lymph node dissection (RPLND). PATIENTS AND
      METHODS: The incidence of abdominal relapse was recorded in 417 men presenting
      with stage 1 NSGCT over the past 18 years. Up to 1986, 161 men were managed by
      surveillance alone, and abdominal relapse occurred in 26. From 1986 onwards, men
      with positive risk factors in the orchidectomy specimen were offered two courses
      of chemotherapy; 60 accepted and one relapsed in the abdomen, and 196 underwent
      surveillance and 19 relapsed in the abdomen. RESULTS: Abdominal relapse was
      significantly reduced from 16% before 1986 to 8% afterward (P = 0.014). Mortality
      from testicular tumour or treatment toxicity remained low, at 0.6% before 1986
      and 2.0% since then. CONCLUSION: The need for RPLND in stage 1 NSGCT remains
      highly doubtful.

PMID- 10886091
TI  - Paediatric urinary tract infection and the necessity of complete urological
      imaging.
AB  - OBJECTIVE: To evaluate voiding cysto-urethrography (VCUG) in assessing children
      with urinary tract infection (UTI) when renal/bladder ultrasonography and renal
      scintigraphy show no abnormality. PATIENTS AND METHODS: A total of 468 renal
      scintigrams taken in children for an indication of UTI between January 1996 and
      December 1998 were reviewed. The renal and bladder ultrasonograms of those
      children with a normal renal scan were then reviewed. Children with both normal
      renal scans and normal ultrasonography were then evaluated for the frequency and
      grade of vesico-ureteric reflux (VUR) on VCUG. RESULTS: Of the 468 patients, 453
      (97%) had complete imaging studies; 152 of the children evaluated had normal
      renal scans, of whom 101 had a normal renal ultrasonogram. Twenty-three (23%)
      children with both a normal renal scan and renal/bladder ultrasonogram showed VUR
      on VCUG, of whom 14 had bilateral VUR and 13 grade III or higher VUR. CONCLUSION:
      This study indicates that about 23% of patients may have significant VUR despite
      both a normal renal scan and ultrasonogram. Therefore, VCUG remains important in
      evaluating and managing children with UTI.

PMID- 10886092
TI  - Endothelins in the urinary tract.

PMID- 10886094
TI  - Simultaneous recording of mechanical and intracellular electrical activity in
      human urinary bladder smooth muscle.
AB  - OBJECTIVE: To elucidate the role of the membrane potential in human detrusor
      smooth muscle contraction, by simultaneously recording mechanical and
      intracellular electrical activity in muscle strips. Materials and methods The
      agonists acetylcholine and carbachol were applied to induce a contraction on
      muscarinic receptor stimulation; to block the response, atropine was added to the
      bath. The Ca2+ necessary for activating the contractile machinery can be
      recruited via two pathways: release from intracellular stores or influx from the
      extracellular matrix. High potassium was applied to induce Ca2+ influx through
      voltage-sensitive Ca2+ channels. RESULTS: There were significant changes in the
      force when agonist, antagonist and high potassium was administered. However,
      there were significant changes in membrane potential only when KCl was applied to
      the bath and not with muscarinic agonist or antagonist application. Activity in
      the form of spike potentials did not change significantly on applying any of the
      test substances. CONCLUSION: The present results indicate that the Ca2+ mobilized
      on M3 receptor stimulation originates primarily from intracellular stores, with
      no systematic changes in membrane potential. Atropine only caused a relaxation in
      muscle previously contracted by M3-receptor agonist stimulation; it had no effect
      on relaxed muscle strips.

PMID- 10886093
TI  - Cloacal and urogenital malformations in adriamycin-exposed rat fetuses.
AB  - OBJECTIVES: To determine the spectrum of cloacal and urogenital malformations in
      rat fetuses prenatally exposed to adriamycin, which causes abnormalities that
      strongly resemble the VATER association (vertebral defects, anal atresia, tracheo
      oesophageal fistula with oesophageal atresia, renal defects and radial limb
      dysplasia) in humans, and to evaluate how closely such anomalies resemble those
      seen in humans. MATERIALS AND METHODS: Timed-pregnant rats were injected
      intraperitoneally with adriamycin at 6-9 days of gestation; a control group
      received saline only. Fetuses (35 treated and 30 control) were recovered at 21
      days of gestation, and examined macroscopically and microscopically for cloacal
      and urogenital abnormalities. RESULTS: All the treated fetuses had no bladders
      and severe hydroureter/hydronephrosis on one or both sides. Male fetuses had a
      proximal blind-ending urethra communicating with dilated ureters and giving rise
      to vasa. Female fetuses had a persistent urogenital sinus communicating with the
      ureters and cervix/uterus; 57% of the treated group had an imperforate anus and
      some had recto-urethral fistulae (males) or recto-urogenital fistulae (females).
      CONCLUSION: Rat fetuses exposed to adriamycin have a spectrum of cloacal and
      urogenital anomalies (predominantly no bladder) which is more severe than those
      of the human VATER association. Nonetheless, this is an excellent animal model
      for the study of genitourinary embryology, especially bladder development.

PMID- 10886095
TI  - Time-specific effects of mono-n-butyl phthalate on the transabdominal descent of
      the testis in rat fetuses.
AB  - OBJECTIVE: To determine the time-specific effects of mono-n-butyl phthalate (MBP)
      on the transabdominal migration of the testis in fetal rats. Materials and
      methods Three groups of pregnant rats were administered MBP by stomach-tube
      feeding when the fetus was at 7-10 days of gestation in group 1, 11-14 days in
      group 2, and 15-18 days in group 3; controls (group 4) were given vehicle only
      from 7-18 days. At 20 days of gestation the fetuses were obtained by Caesarean
      section, and the position of the testes, the development of the gubernaculum,
      cranial suspensory ligament and the epididymis were examined. RESULTS: The timed
      intervals of MBP administration showed that the maximum inhibition of
      transabdominal testicular descent was at 15-18 days of gestation. There was an
      elongated gubernaculum and hypertrophic cranial suspensory ligament in the MBP
      treated rat fetuses. Furthermore, the epididymis showed a few small ducti
      deferentia, although there were no remarkable changes in either the Sertoli and
      Leydig cells in these testes. The mean (SEM) content of testicular testosterone
      was significantly less (P < 0.001) in the MBP-treated rats, at 50.9 (3.8)
      pg/testis, than in the controls, at 676 (33.3) pg/testis. CONCLUSIONS: These
      findings indicate that a brief exposure to MBP during fetal development can
      inhibit the transabdominal migration of the testis and reduce testosterone
      content in rats, although the relationship between migration and the testicular
      testosterone content remains unknown.

PMID- 10886096
TI  - The morphological changes in rat bladder after photodynamic therapy with 5
      aminolaevulinic acid-induced protoporphyrin IX.
AB  - OBJECTIVE: To assess the optimum light energy needed to induce only superficial
      bladder wall damage during photodynamic therapy (PDT) as a treatment for bladder
      cancer. Materials and methods The urinary bladder (with normal epithelium) of 64
      female rats was treated with PDT using a continuous-wave argon-ion laser as an
      energy source and aminolaevulinic acid (ALA)-induced protoporphyrin IX
      photosensitizer. Four hours after the intravenous administration of ALA (300
      mg/kg) the bladders were intravesically exposed to light fluences of 20-80 J/cm2.
      The control rats received no ALA and were exposed to 20 J/cm2 light. After 1, 3,
      7 and 21 days the animals were killed and the morphological changes in bladder
      wall analysed both macroscopically and using light and scanning electron
      microscopy. RESULTS: At the dose of ALA given, a fluence of 20-40 J/cm2 caused
      mainly superficial damage, whereas 80 J/cm2 produced full-thickness injuries to
      the bladder wall. The maximum effect of PDT occurred after 1 and 3 days of
      irradiation. After 3 weeks of PDT the histology showed few full-thickness
      injuries and only in those treated with 80 J/cm2 light. CONCLUSION: These results
      indicate that PDT can be used to safely induce a selective superficial removal of
      bladder mucosa with no fibrotic effects on detrusor musculature, when optimum
      photosensitizing drug and fluences are used. These findings support the use of
      PDT in the therapy of superficial bladder cancer.

PMID- 10886097
TI  - Effects of androgen and ageing on gene expression of vasoactive intestinal
      polypeptide in rat corpus cavernosum.
AB  - OBJECTIVE: To clarify the effects of androgens (testosterone and
      dihydrotestosterone, DHT) and ageing on gene expression of vasoactive intestinal
      polypeptide (VIP), assessed as the expression of VIP mRNA, in rat corpus
      cavernosum. Materials and methods The study comprised 160 male Sprague Dawley
      rats divided into group A (56 rats, 5 weeks old), group B (50 rats, 10 weeks old)
      and group C (54 rats, 58 weeks old). Groups A-C were subdivided, respectively,
      into subgroups 1 (intact controls), 2 (castrated), 3 (castrated but given
      testosterone undecanoate 25 mg/kg per month by intramuscular injection), 4
      (castrated with testosterone undecanoate 50 mg/kg per month) and 5 (treated with
      finasteride 4.5 mg/kg per day, orally). At 4 and 10 weeks after these treatments
      half the rats were killed. Serum samples were taken for the measurement of total
      and free testosterone and DHT, using a radioimmunoassay. Penile samples (corpus
      cavernosum) were frozen in liquid nitrogen and stored at -80 degrees C. VIP mRNA
      was estimated using a semi-quantitative reverse-transcription polymerase chain
      reaction. RESULTS: There was no significant difference in VIP mRNA in rat corpus
      cavernosum between intact control and castrated subgroups, or subgroups treated
      with finasteride, in groups A-C, including both the 4- and 10-week old animals (P
      > 0.05). Penile VIP mRNA was unchanged at any dose of testosterone in the
      castrated subgroups in all groups (P > 0.05). There was no significant
      relationship between penile VIP mRNA and ageing (P > 0.05). CONCLUSIONS: The gene
      expression of VIP in rat corpus cavernosum is independent of androgens
      (testosterone and DHT) and ageing. Androgens probably induce penile erection by
      pathways other than VIP; ageing may have little effect on penile VIP mRNA.

PMID- 10886098
TI  - The concealed laparoscopic orchidopexy.

PMID- 10886099
TI  - Vesical necrosis after hydrodistension of the urinary bladder in a patient with
      interstitial cystitis.

PMID- 10886101
TI  - EDITOR'S COMMENT

PMID- 10886100
TI  - Tumour of the spermatic cord: an unusual primary manifestation of an epithelial
      mesothelioma of the peritoneum with patent processus vaginalis.

PMID- 10886102
TI  - Inherited renal cancer.

PMID- 10886103
TI  - New developments in the use of monoclonal antibodies in the therapy of
      genitourinary cancer.

PMID- 10886104
TI  - Vanilloids and the overactive bladder.

PMID- 10886106
TI  - New developments in the use of monoclonal antibodies in the therapy of
      genitourinary cancer

PMID- 10886105
TI  - The management of prostate cancer in patients with a rising prostate-specific
      antigen level.

PMID- 10886107
TI  - Inherited renal cancer

PMID- 10886108
TI  - Vanilloids and the overactive bladder

PMID- 10886109
TI  - The management of prostate cancer in patients with a rising prostate-specific
      antigen level

PMID- 10886111
TI  - The acute vascular effects of frusemide in heart failure.

PMID- 10886110
TI  - The impact of molecular medicine upon early cardiovascular drug development.

PMID- 10886112
TI  - Towards a blood test for heart failure: the potential use of circulating
      natriuretic peptides.

PMID- 10886113
TI  - Diurnal variation in the quantitative EEG in healthy adult volunteers.
AB  - AIMS: To define the change in power in standard waveband frequencies of
      quantitative cortical electroencephalogram (EEG) data over a 24 h period, in a
      drug free representative healthy volunteer population. METHODS: This was an open,
      non randomised study in which 18 volunteers (9 male and 9 female) were studied on
      1 study day, over a 24 h period. Volunteers had a cortical EEG recording taken at
      0, 2, 4, 6, 8, 10, 12, 16 and 24 h. Each recording lasted for 6 min (3 min eyes
      open, 3 min eyes closed). All EEG recordings were taken in a quietened ward
      environment with the curtains drawn round the bed and the volunteer supine.
      During the 3 min eyes open, volunteers were asked to look at a red circle on a
      screen at the foot of the bed, and refrain from talking. RESULTS: Plots produced
      of geometric mean power by time of the standard wave band frequencies gave some
      indication of a circadian rhythm over the 24 h period for theta (4. 75-6.75 Hz),
      alpha1 (7.0-9.5 Hz) and beta1 (12.75-18.50 Hz) wavebands. Mixed models were
      fitted to both the eyes open and eyes closed data which confirmed a change in
      mean waveband power with time with statistical significance at the conventional
      5% level (P < 0.05). CONCLUSIONS: These data indicate the presence of a diurnal
      variation in the cortical quantitative EEG. They support the use of a placebo
      control group when designing clinical trials which utilize quantitative EEG to
      screen for central nervous system (CNS) activity of pharmaceutical agents, to
      control for the confounding variable of time of day at which the EEG recordings
      were made.

PMID- 10886114
TI  - Constriction to ETB receptor agonists, BQ-3020 and sarafotoxin s6c, in human
      resistance and capacitance vessels in vivo.
AB  - AIMS: The aim of the study was to examine the effects of the ETB receptor
      selective agonists sarafotoxin S6c (SFTX6c) and BQ-3020 on the forearm resistance
      and capacitance vessels in healthy subjects in vivo. METHODS: The local response
      to intra-arterial or intravenous infusion of SFTX6c (5 pmol min-1) or BQ-3020 (50
      pmol min-1) was assessed, on separate occasions, in eight healthy men (aged 20-28
      years). Data (mean +/- s.e.mean) were examined by ANOVA. Results are expressed as
      percentage change from baseline at 90 min. RESULTS: SFTX6c and BQ-3020 reduced
      forearm blood flow, following local intra-arterial infusion (-25 +/- 7% and -27
      +/- 7%, respectively; P < 0.001) and reduced hand vein diameter, following local
      intravenous infusion (-30 +/- 8% and -16 +/- 7%, respectively; P < 0.001).
      CONCLUSIONS: We have shown that locally active infusions of the selective ETB
      receptor agonists SFTX6c and BQ-3020 cause arterial constriction and
      venoconstriction in healthy human blood vessels in vivo. These results indicate
      that ETB receptor stimulation may mediate vasoconstriction in humans.

PMID- 10886115
TI  - Frequencies of CYP2D6 mutant alleles in a normal Japanese population and
      metabolic activity of dextromethorphan O-demethylation in different CYP2D6
      genotypes.
AB  - AIMS: To determine the frequencies of 11 CYP2D6 mutant alleles (CYP2D6*2, *3, *4,
      *5, *8, *10, *11, *12, *14, *17 and *18), and their relation to the metabolic
      capacity of CYP2D6 in Japanese subjects. METHODS: One hundred and sixty-two
      unrelated healthy Japanese subjects were genotyped with the polymerase chain
      reaction amplification method and 35 subjects were phenotyped with
      dextromethorphan. RESULTS: The frequencies of CYP2D6*2,*5, *10 and *14 were 12.9,
      6.2, 38.6 and 2.2% in our Japanese subjects, respectively. CYP2D6*3, *4, *8, *11,
      *12, *17 and *18 were not detected. The mean log metabolic ratio of
      dextromethorphan in subjects with genotypes predicting intermediate metabolizers
      was significantly greater than that of heterozygotes for functional and defective
      alleles. CONCLUSIONS: CYP2D6*5 and CYP2D6*14 are the major defective alleles
      found in Japanese subjects. In addition, CYP2D6*10 may play a more important role
      than previously thought for the treatment of Japanese patients with drugs
      metabolized by CYP2D6.

PMID- 10886116
TI  - The incidence of adverse events and risk factors for upper gastrointestinal
      disorders associated with meloxicam use amongst 19,087 patients in general
      practice in England: cohort study.
AB  - AIMS: Meloxicam is a novel nonsteroidal anti-inflammatory drug (NSAID) which may
      be associated with fewer adverse upper gastrointestinal events than other NSAIDs
      because it preferentially inhibits the inducible enzyme cyclo-oxygenase-2
      relative to the constitutive isoform, cyclo-oxygenase-1. The aims of the study
      were to: determine the rate of adverse events associated with meloxicam in
      general practice, stratify these rates by selected risk factors, and to identify
      signals of previously unsuspected adverse events associated with meloxicam.
      METHODS: As part of the national prescription-event monitoring pharmacovigilance
      system for newly launched drugs in general practice, all patients prescribed
      meloxicam in England between December 1996 and March 1997 were identified by the
      central Prescription Pricing Authority. We sent short questionnaires to all
      prescribers asking about adverse events experienced within 6 months of the first
      prescription. RESULTS: There were 19 087 patients in the study. The rate of
      dyspepsia during the first month of exposure was 28.3 per 1000 patient-months.
      There were 33 reports of upper gastrointestinal haemorrhage during treatment
      (rate: 0.4 per 1000 months). A history of gastrointestinal disorder in the
      previous year was associated with an increased rate of dyspepsia (rate ratio:
      3.0; 95% confidence interval: 2.6, 3.4), abdominal pain (2.1; 1.6, 2.6), and
      peptic ulcer (4.0; 1.4, 13.2). Prior NSAID use was associated with a 20-30%
      decrease in the rate of dyspepsia and abdominal pain in patients starting
      meloxicam, while patients prescribed concomitant gastroprotective agents had a
      two to three-fold increased rate of dyspepsia, abdominal pain and peptic
      ulceration. Other rare events were thrombocytopenia (n = 2); interstitial
      nephritis (n = 1) and idiosyncratic liver abnormalities (n = 1). CONCLUSIONS: In
      the absence of gastro-intestinal risk factors the incidence of gastro-intestinal
      disturbance was low. Such risk factors should be carefully reviewed prior to
      prescribing meloxicam.

PMID- 10886117
TI  - Intracranial haemorrhage and use of selective serotonin reuptake inhibitors.
AB  - AIMS: In the past few years an increasing number of bleeding disorders have been
      reported in association with the use of selective serotonin reuptake inhibitors
      (SSRIs), including serious cases of intracranial haemorrhage, raising concerns
      about the safety of this class of drugs. The present study was performed to test
      the hypothesis of an increased risk of intracranial haemorrhage associated with
      the use of SSRIs. METHODS: We carried out a case-control study nested in a cohort
      of antidepressants users with the UK-based General Practice Research Database
      (GPRD) as the primary source of information. The study cohort encompassed
      subjects aged between 18 and 79 years who received a first-time prescription for
      any antidepressant from January, 1990 to October, 1997. Patients with presenting
      conditions or treatments that could be associated with an increased risk of
      intracranial haemorrhage were excluded from the cohort. Patients were followed-up
      until the occurrence of an idiopathic intracranial haemorrhage. Up to four
      controls per case, matched on age, sex, calendar time and practice were randomly
      selected from the study cohort. We estimated adjusted odds ratios and 95%
      confidence intervals of intracranial haemorrhage with current use of SSRIs and
      other antidepressants as compared with nonuse using conditional logistic
      regression. RESULTS: We identified 65 cases of idiopathic intracranial
      haemorrhage and 254 matched controls. Current exposure to SSRIs was ascertained
      in 7 cases (10. 8%) and 24 controls (9.7%) resulting in an adjusted OR (95%CI) of
      0. 8 (0.3,2.3). The estimate for 'other antidepressants' was 0.7 (0.3,1. 6). The
      effect measures were not modified by gender or age. No effect related to dose or
      treatment duration was detected. The risk estimates did not change according to
      the location of bleeding (intracerebral or subarachnoid). CONCLUSIONS: Our
      results are not compatible with a major increased risk of intracranial
      haemorrhage among users of SSRIs or other antidepressants at large. However,
      smaller but still relevant increased risks cannot be ruled out.

PMID- 10886118
TI  - Feasibility study of multicentre comparison of NHS hospital pharmacy computer
      data.
AB  - AIMS: This study aims to determine the feasibility of collecting, collating and
      analysing drug expenditure data from a sample of acute hospitals in England.
      METHODS: The hospital pharmacy computer system was used to report on drug
      expenditure from 16 hospitals throughout England for a 2 year period. These data
      were analysed as a whole and hospital episode statistics were correlated to
      hospital drug costs. RESULTS: Hospital outpatient costs were found to be
      approximately one third of hospital inpatient costs. Cardiovascular drugs
      accounted for the greatest increase in expenditure for both inpatients and
      outpatients (25%). The most expensive therapeutic area of drug use across all
      sites was anti-infectives. The average daily number of occupied beds explained
      55% of the variation in inpatient expenditure and the number of outpatient
      (including Accident and Emergency) attendances explained 60% of the outpatient
      drug expenditure. CONCLUSIONS: This project has confirmed the feasibility of
      collecting, collating and analysing hospital drug expenditure and identified some
      interesting patterns and trends in hospital drug use. Hospital activity is
      reflected in hospital drug costs.

PMID- 10886119
TI  - Nonprescription medicine use in a multiple sclerosis clinic population.
AB  - AIMS: To determine the use of nonprescription medicines in a cohort of multiple
      sclerosis (MS) patients and to identify a subgroup of patients liable to spend
      more on nonprescription medicines METHODS: A questionnaire was given to MS
      patients attending a neurology out-patients clinic during the previous year.
      Medicines from a General Practitioner (GP), pharmacy and 'other' sources utilized
      in the last month were determined, along with demographic data. Additional
      information was obtained from hospital notes. RESULTS: One hundred and seventeen
      MS patients responded to the questionnaire, giving a response rate of 79%
      (117/148). Responders differed from nonresponders only in age, with responders
      being significantly older than nonresponders (P = 0.011). Over one-third of
      medicines taken in the last month were nonprescription medicines (35%; 219/627).
      A gamolenic acid containing preparation was the most popular, purchased by 28% of
      patients. Fifteen percent (17/117) of MS patients had exceeded the recommended
      daily allowance of a vitamin (frequently vitamins A, D and E), and one exceeded
      the upper safe level for daily self-supplementation of vitamin A and D. Females
      spent significantly more than males in the previous month ( pound10. 09 compared
      with pound5.53, respectively; P = 0.022). Patients who were older, reported
      worsening MS symptoms in the last year and those who exhibited greater disability
      were more likely to have been prescribed medicines by a GP (P < 0.0005), although
      they were not more likely to self-prescribe or take alternative remedies (P > 0.
      05). However, those with poorer mobility were significantly less likely to have
      purchased a pharmacy medicine in the last month (P = 0.033). CONCLUSIONS: MS
      patients were high users of nonprescription medicines. A typical subgroup of MS
      patients that spent more on nonprescription medicines could not be identified,
      aside from females. Furthermore, the strong predictors for increased use of
      prescription medicines (increasing age, severity of symptoms in the last year and
      poorer mobility) were not found for nonprescription medicines. Excessive intake
      of the fat soluble vitamins could lead to hypervitaminosis, the effects of which
      could exacerbate or mimic MS symptoms. Health professionals should be aware of
      these issues and counsel the MS patient accordingly, particularly as the majority
      purchased products from 'other' sources where typically there is no health
      professional available to give advice. The limited use of pharmacy medicines by
      the more disabled patient could indicate a problem with access to the pharmacy,
      or could reflect the greater use of prescription medicines.

PMID- 10886120
TI  - Comparison of the neurokinin-1 antagonist GR205171, alone and in combination with
      the 5-HT3 antagonist ondansetron, hyoscine and placebo in the prevention of
      motion-induced nausea in man.
AB  - AIMS: In man a neurokinin-1 (NK1) receptor antagonist has previously been shown
      to be ineffective in the prevention of motion-induced nausea. The antiemetic
      efficacy of NK1 receptor antagonists against chemotherapy-induced emesis is,
      however, enhanced when combined with a 5-HT3 receptor antagonist. Hence the
      efficacy of the NK1 antagonist GR205171 in combination with the 5-HT3 antagonist
      ondansetron (Zofrantrade mark) was assessed in motion-induced nausea. METHODS:
      GR205171 25 mg i.v., with and without concomitant administration of ondansetron 8
      mg i.v., and hyoscine hydrobromide 0. 6 mg orally (positive control) were
      compared with placebo in a model of motion-induced nausea. The study was
      performed to a four-period, randomized, balanced, double-blind, crossover design
      in 16 healthy subjects. The end-point was the exposure to the motion stimulus
      required to produce moderate nausea in the subjects. RESULTS: The motion stimulus
      required to produce moderate nausea was significantly greater for the positive
      control than placebo (P < 0. 001). There was no significant difference between
      either GR205171 or GR205171 plus ondansetron and placebo (P = 0.648 and 0.342,
      respectively). CONCLUSIONS: The enhancement of NK1 receptor antagonist antiemetic
      activity through combination with a 5-HT3 receptor antagonist is not replicated
      in motion-induced nausea.

PMID- 10886121
TI  - Comparison of the effects of clonidine and yohimbine on pupillary diameter at
      different illumination levels.
AB  - AIMS: To evaluate the pupillary effects of single doses of the alpha2
      adrenoceptor agonist clonidine and the alpha2-adrenoceptor antagonist yohimbine
      under several illumination conditions. METHODS: Sixteen healthy male volunteers
      received clonidine 0.2 mg, yohimbine 22 mg, clonidine 0.2 mg + yohimbine 22 mg in
      a double-blind placebo-controlled, cross-over study. 2 h post drug ingestion
      pupil diameter was recorded in darkness, and at luminance levels of 6 Cd m-2, 91
      Cd m-2 and 360 Cd m-2. The effects of the active treatments on pupil diameter
      were also expressed as the differences from the placebo condition ('placebo
      corrected' data; mean [95% CI]). RESULTS: Clonidine had little effect on pupil
      diameter in darkness; however, it caused a significant, light-dependent, miosis
      when the eye was illuminated. On the other hand yohimbine increased pupil size;
      this increase was significant at 91 and 360 Cd m-2. There were no significant
      differences between the effects of the combined treatment (clonidine 0.2 mg +
      yohimbine 22 mg) and the effect of placebo. CONCLUSIONS: The pupillary effects of
      clonidine and yohimbine are likely to reflect the interaction of these drugs with
      inhibitory alpha2-adrenoceptors located on central noradrenergic neurones, which
      in turn would lead to a decrease and an increase, respectively, in sympathetic
      outflow to the iris. The light dependence of the pupillary effects of these
      drugs, however, suggests that the parasympathetic light reflex pathway is also
      involved, which is known to be under inhibitory control from the central
      noradrenergic neurones. Modulation of parasympathetic outflow seems to play an
      important role since both drugs had relatively little effect on pupil diameter in
      darkness when sympathetic activity predominates.

PMID- 10886122
TI  - Absorption of lefradafiban from different sites of the gastrointestinal tract.
AB  - AIMS: Fibrinogen receptor antagonists show a close relationship between plasma
      concentrations and inhibitory effect. Optimal efficacy at an acceptable bleeding
      risk requires low inter- and intrasubject variability on low peak trough
      fluctuation in receptor occupancy and therefore also of plasma concentrations.
      Therefore, the enteral absorption of lefradafiban, an orally available fibrinogen
      receptor antagonist prodrug, was investigated after local administrations to
      different sites of the gastrointestinal tract in order to investigate the
      feasibility of an oral extended release formulation. METHODS: Twelve healthy male
      subjects received in a randomised, open-labelled, four-period crossover trial
      four consecutive administrations of lefradafiban: 1. orally; 2. administration
      into the jejunum, 3. administration into the lower jejunum/ileum (300 cm distally
      to the teeth), and 4. administration into the lumen of the sigmoid region (30 cm
      proximally to the anus). Local intestinal administrations were performed through
      a gastrointestinal tube. RESULTS: Compared with oral administration, ratios [mean
      (two-sided 90% confidence intervals)] of maximum drug plasma concentrations and
      AUC(0,24 h) of fradafiban were 1.05 (0.80, 1.39) and 1.06 (0.85,1.31) after
      jejunal, 0.98 (0.75,1.30) and 0.98 (0.79,1.21) after ileal, 0.52 (0.39,0.69) and
      0.68 (0.55,0.85) after colonic administration. Urinary excretion of fradafiban
      was about 16% of the dose after oral, jejunal and ileal applications whereas
      after rectal administration about 11% were excreted. CONCLUSIONS: Lefradafiban is
      absorbed throughout the entire gastrointestinal tract. Therefore, an extended
      release formulation seems to be feasible with regard to bioavailability.

PMID- 10886123
TI  - Ovarian hormones in man: their effects on resting vascular tone, angiotensin
      converting enzyme activity and angiotensin II-induced vasoconstriction.
AB  - AIMS: Oestrogens in women have been shown to cause vasodilation which may reflect
      alterations in the activity of vascular angiotensin converting enzyme (ACE)
      and/or sensitivity to angiotensin II. The aim of this study was to assess the
      effect of ovarian hormones on vascular tone, vascular ACE activity and
      vasoconstriction to angiotensin II in males. METHODS: Eight volunteers were
      randomised in a crossover design to oestradiol, medroxy-progesterone, and
      placebo. Vasoconstriction to angiotensin I and angiotensin II was assessed by
      forearm plethysmography. RESULTS: Although baseline forearm flow was increased
      with oestradiol, suggesting generalized vasodilation, there were no changes in
      the vasoconstrictor responses to angiotensin I or angiotensin II. Medroxy
      progesterone affected neither baseline flow nor vasoconstrictor responses. The
      results expressed as percentage reduction in flow (mean +/- s.d.) were:
      angiotensin I 48 pmol ml-1: placebo -48 +/- 14%; oestradiol -42 +/- 16%;
      medroxyprogesterone -43 +/- 8% and for angiotensin II 16 pmol ml-1: placebo -42
      +/- 10%; oestradiol -39 +/- 11%; medroxyprogesterone -46 +/- 13%. CONCLUSIONS:
      Acute administration of oestradiol caused vasodilation in males, the effect was
      not due to alterations in vascular ACE activity or to altered sensitivity to
      angiotensin II.

PMID- 10886124
TI  - CYP2D6 and CYP2C19 genotypes of patients with terodiline cardiotoxicity
      identified through the yellow card system.
AB  - AIMS: Terodiline has concentration dependent QT prolonging effects and thus the
      potential for cardiotoxicity. Pharmacogenetic variation in terodiline metabolism
      could be responsible for cardiotoxicity. We sought to determine whether CYP2D6
      (debrisoquine hydroxylase) or CYP2C19 (S-mephenytoin hydroxylase) status is a
      risk factor for terodiline cardiotoxicity. METHODS: Using the UK Yellow Card
      scheme to identify patients, blood samples were obtained from eight patients who
      survived ventricular tachycardia or torsades de pointes suspected to be due to
      terodiline, for determination of CYP2D6 and CYP2C19 genotypes. Genotype
      prevalence was compared with that in published general population groups.
      RESULTS: One patient was a CYP2D6 poor metaboliser (CYP2D6*4 homozygous) and a
      second was heterozygous for CYP2D6*4, a slightly lower frequency for these
      genotypes compared with the general population (P = 0.31). In the case of
      CYP2C19, one patient was a poor metaboliser and four were heterozygous for the
      variant CYP2C19*2 allele, compared with general population frequencies of 2% and
      23%, respectively (P = 0.035). CONCLUSIONS: These findings suggest that
      debrisoquine poor metaboliser status is not primarily responsible for terodiline
      cardiotoxicity. However, possession of the CYP2C19*2 allele appears to contribute
      to adverse cardiac reactions to terodiline. The present study demonstrates the
      feasibility of using spontaneous adverse drug reaction reporting schemes to
      determine the contribution of genotype for metabolizing enzymes to uncommon
      adverse drug reactions.

PMID- 10886125
TI  - Angioedema and cough in Nigerian patients receiving ACE inhibitors.

PMID- 10886126
TI  - A drug interaction between fusidic acid and a combination of ritonavir and
      saquinavir.

PMID- 10886127
TI  - Osler and the skin.
AB  - William Osler was the greatest physician of his time. Specialists reading his
      textbooks agreed that in their own specialities he was accurate and illuminating.
      His grasp of dermatology was particularly striking and skin changes are prominent
      in five of the syndromes named after him and in at least 100 of his papers. This
      paper describes how his early training in dermatology under Tilbury Fox in London
      and Hebra in Vienna combined with his unusual personal qualities to enable him to
      make massive contributions to a wide variety of dermatological topics. These
      include smallpox, cutaneous tuberculosis, nail growth, leprosy, scleroderma,
      pigmentation and purpuric eruptions as well as the more obvious hereditary
      haemorrhagic telangiectasia, angio-neurotic oedema and Osler's nodes.

PMID- 10886128
TI  - Thomas Bateman MD FLS 1778-1821.
AB  - Thomas Bateman was a physician to the Carey Street Public Dispensary with Robert
      Willan in the first decade of the nineteenth century when the latter was
      developing the classification that would act as a foundation for modern
      dermatology. Following Willan's death with his work still incomplete, Bateman
      published a book, as an abstract of Willan's full concept, which was probably the
      most influential dermatology text of the nineteenth century. This was the first
      classification of dermatology that precisely defined the terms used and fitted
      individual diseases into a single class, rather than considering different stages
      of the same disease as maladies that belonged in different classes. This was the
      first attempt to link treatment to the disease process rather than to the
      clinical appearances and thus represents the origin of modern scientific clinical
      dermatology.

PMID- 10886130
TI  - Rupert Hallam and the development of dermatology in Sheffield.
AB  - (Arthur) Rupert Hallam worked as a dermatologist in Sheffield from 1911 to 1944.
      Early in his career, he also specialized in diagnostic radiology and established
      this speciality in Sheffield. Hallam performed investigative work on the
      aetiology of papular urticaria and erythema multiforme, the prognosis of
      psoriasis, and the aetiology of chilblains. He was an original member of the
      British Association of Dermatologists from 1920 becoming president in 1935. He
      also helped to found the North of England Dermatological Society. He was an
      innovator in both clinical and administrative matters and was the first British
      dermatologist to develop a full-time training post in the specialty.

PMID- 10886129
TI  - Hutchinson and Nettleship, Nettlerash and albinism.
AB  - With specialization still in its infancy, Victorian surgeons were often concerned
      with the diagnosis and care of skin disorders. The careers of three London
      surgeons from successive generations, Sir James Paget, Sir Jonathan Hutchinson
      and Edward Nettleship are discussed with emphasis on their mutual influence and
      contributions to dermatology. Nettleship's original description of urticaria
      pigmentosa and his research into the inheritance of albinism are reviewed in more
      detail.

PMID- 10886131
TI  - 'Brooke of Manchester'.
AB  - We present a brief account of the life and times of Dr Henry Grundy Brooke, a
      Manchester dermatologist and key figure in British dermatology in the nineteenth
      century. Our report highlights the achievements of a man whose contributions to
      dermatology continue to be of relevance in the new millennium.

PMID- 10886132
TI  - Turning points in dermatology during the 20th century.

PMID- 10886133
TI  - Genetics, past and present, and the rise of systems dermatology.

PMID- 10886134
TI  - The immunopharmacology of skin inflammation: the future is already here!

PMID- 10886135
TI  - Guidelines for the management of tinea capitis. British Association of
      Dermatologists.
AB  - These guidelines for the management of tinea capitis have been prepared for
      dermatologists on behalf of the British Association of Dermatologists. They
      present evidence-based guidance for treatment, with identification of the
      strength of evidence available at the time of preparation of the guidelines, and
      a brief overview of epidemiological aspects, diagnosis and investigation.

PMID- 10886136
TI  - The role of lymphocytes in human dermal wound healing.
AB  - BACKGROUND: Animal experimental data indicate a requirement for functionally
      active T lymphocytes to allow optimal healing of dermal wounds. Little evidence
      exists to confirm that this is the case in humans. Lymphocyte involvement in
      regulation of healing is probably mediated by release of secreted
      cytokines/growth factors, and we hypothesize that the cytokine profile
      requirement will be modulated as healing progresses. OBJECTIVES: As this is
      likely to be reflected in lymphocyte subset changes over the course of normal
      healing, we investigated the immunophenotype of lymphocyte subpopulations during
      wound healing. METHODS: Sequential biopsies were taken over 42 days from the
      margin of 12 wounds healing by secondary intention after pilonidal sinus
      excision. Serial biopsy sections were analysed by immunohistochemistry using
      lymphocyte-specific monoclonal antibodies, and lymphocytes were counted
      microscopically. RESULTS: Within 42 days, the mean decrease in wound volume was
      87.5%. This was accompanied by significant changes in the wound margin lymphocyte
      population. Total numbers (mean +/- SEM) of T lymphocytes decreased from 36.8 +/-
      9.8 cells per field at inclusion in the study to 25.9 +/- 3.0 immediately prior
      to wound closure, with a concomitant increase in B lymphocytes from 1 +/- 0.4 to
      9.5 +/- 3.6 cells per field. The CD4/CD8 T-lymphocyte ratio fell from an initial
      level of 3.6 +/- 0.3 to 2.1 +/- 0.3 (mean +/- SEM) prior to closure. CONCLUSIONS:
      These data indicate that human wound-associated lymphocyte populations are
      modulated during healing; the increase in numbers of CD8+ T-suppressor
      lymphocytes is in accordance with previous animal data, indicating a role for
      these cells in downregulating healing as the wound closes. This study also
      documents an associated increase in B lymphocytes and healing of human wounds,
      with an as yet undefined role.

PMID- 10886137
TI  - Sphingosylphosphorylcholine stimulates contraction of fibroblast-embedded
      collagen gel.
AB  - Sphingosylphosphorylcholine (SPC), a sphingolipid metabolite, has recently been
      reported to stimulate wound healing in an animal model. To clarify the mechanism
      of SPC on the healing process, we examined the effect of SPC on wound contraction
      using an in vitro model. A mixture of human dermal fibroblasts and porcine type I
      collagen in a serum-free medium was gelled, and then separated from the well
      after a 12-h incubation. Various reagents were applied to the medium, and its
      contractile activity was analysed by measuring the amount of contracted surface
      area. Among the sphingolipid metabolites, SPC and sphingosine-1-phosphate, but
      not sphingosine, C2-ceramide and C6-ceramide, stimulated collagen gel
      contraction. Maximal gel contraction, observed at 10 micromol L-1 of SPC,
      occurred as early as 1 h after the treatment and persisted for more than 48 h.
      The effect of SPC was not inhibited by pretreatment with antitransforming growth
      factor-beta or antiplatelet-derived growth factor-BB antibodies. Among the
      various signal transduction inhibitors, pertussis toxin, staurosporine and H7
      were found to inhibit the action of SPC, whereas genistein and tyrphostin A47
      were not, suggesting that fibroblast contraction induced by SPC is mediated by a
      trimeric guanosine triphosphate-binding protein (G protein)-coupled receptor and
      protein kinase. Our findings imply that the effect of SPC as a healing stimulant
      might be due in part to stimulation of fibroblast contraction in granulation
      tissue.

PMID- 10886138
TI  - Hexafluoro-1,25-dihydroxyvitamin D3 has markedly increased potency in inhibiting
      proliferation of cultured human keratinocytes compared with 1,25-dihydroxyvitamin
      D3.
AB  - BACKGROUND: Although topical 1,25-dihydroxyvitamin D3 (calcitriol, 1, 25(OH)2D3)
      and its analogues, calcipotriol and tacalcitol, are effective for patients with
      psoriasis, some patients show little or no response. There is a need to develop
      more potent analogues of 1, 25(OH)2D3. Hexafluoro-1,25(OH)2D3 (F6-1,25(OH)2D3) is
      at least 10 times more potent than 1,25(OH)2D3 on calcium metabolism. OBJECTIVES:
      We were interested in whether F6-1,25(OH)2D3 was also more potent than
      1,25(OH)2D3 in inhibiting normal human and psoriatic keratinocyte proliferation.
      METHODS: The antiproliferative activity of F6-1,25(OH)2D3 and 1,25(OH)2D3 was
      determined by 3H-thymidine incorporation into keratinocyte DNA and by counting
      basal cells. RESULTS: F6-1,25(OH)2D3 was approximately 10-fold more active and
      had a longer lasting antiproliferative effect than 1,25(OH)2D3 on normal human
      keratinocytes, and was about 100-fold more potent than 1, 25(OH)2D3 on human
      psoriatic keratinocytes as determined by 3H-thymidine incorporation. F6
      1,25(OH)2D3 also caused a dose-dependent decrease in the number of basal cells
      and was 100-fold more active than 1,25(OH)2D3. CONCLUSIONS: The increased potency
      and the long-lasting effects of F6-1,25(OH)2D3 suggest that F6-1,25(OH)2D3 may be
      a potent candidate agent for treating psoriasis.

PMID- 10886139
TI  - Nail bed keratinocytes express an antigen of the carcinoembryonic antigen family.
AB  - Using a panel of monoclonal and polyclonal antibodies raised against human
      carcinoembryonic antigen (CEA) and CEA-related molecules, we detected strong
      expression of an antigen, with immunoreactivity consistent with non-specific
      cross-reacting antigen (NCA) (CD66c), in all of 26 normal human nail specimens
      obtained from various fingers and toes. In longitudinal sections, strong and
      constant expression of the NCA-like antigen was seen on keratinocytes distributed
      in the upper epithelial cell layers of the nail bed, while in transverse sections
      the expression was limited to the major central portions of the nail bed, but
      only where longitudinal epidermal ridges were observed. In the hyponychium and
      the ventral aspect of the proximal nail fold, the expression was weak or lacking.
      No expression was seen in the nail matrix, the nail plate, or the dorsal aspect
      of the proximal nail fold. The same results were obtained for all of the 26 nails
      studied. This report is the first to demonstrate that an antigen of the CEA
      family, with NCA-like immunoreactivity, is expressed in a specific subpopulation
      of keratinocytes in the nail bed. The specific expression pattern suggests that
      the antigen may play a part in adhesion of the nail plate to the nail bed.

PMID- 10886140
TI  - Cytological alterations in dermal dendrocytes in vitro: evidence for
      transformation to a non-dendritic phenotype.
AB  - Dermal dendrocytes (DDs) are bone marrow-derived cells which are abundant in
      normal human and murine dermis, where they are closely associated with mast cells
      in the perivascular space. The biological role of DDs remains enigmatic. DDs
      express coagulation factor XIIIa and the recently described von Willebrand factor
      receptor, GPIb alpha, potentially indicating a function in tissue repair and
      haemostasis, although participation in antigen presentation is also speculated.
      In healing wounds and 'fibrohistiocytic' tumours, such as dermatofibromas, DDs
      are often associated with non-dendritic histiocytes, some of which also express
      factor XIIIa (FXIIIa). We have utilized human skin organ culture to examine the
      effects of various biological mediators on cytological characteristics of DDs. It
      was found that by 24 h in organ culture, immunoreactive DDs begin to lose their
      dendritic shape, assuming more rounded contours. This phenomenon was accentuated
      by mast cell degranulation; was independent of the nature of mast cell
      secretagogue; and could not be reproduced by recombinant tumour necrosis factor
      alpha, a cytokine known to increase FXIIIa expression in DDs. Like their
      dendritic precursors, non-dendritic cells expressed variable FXIIIa, CD34 and
      CD68 and did not express CD1a or CD45. By ultrastructure, non-dendritic cells
      that develop in vitro resembled non-degenerating monocytes containing occasional
      primary lysosomes and lipid inclusions, and like DDs, expressed fibronexus-like
      plaques on the cell membrane. Transition of DDs from dendritic to non-dendritic
      cells as a consequence of specific microenvironmental influences may provide
      insight into the frequent concurrence of these two cytological types in
      fibrohistiocytic tissue reactions and neoplasia.

PMID- 10886141
TI  - Cytokine profiles in spontaneously regressing basal cell carcinomas.
AB  - BACKGROUND: Basal cell carcinomas (BCCs) can cause considerable morbidity due to
      their ability to enlarge progressively and to destroy underlying tissues.
      However, some BCCs may undergo spontaneous regression in the absence of therapy
      capable of inducing antineoplastic effects. Histological criteria for this
      process have been described, and previous studies have suggested that it may be
      mediated by infiltrating activated CD4-positive T cells. OBJECTIVES: The purpose
      of this study was to compare the expression of cytokines in actively regressing
      and non-regressing BCCs, to ascertain if active regression is associated with a
      particular cytokine profile. METHODS: Reverse transcriptase-polymerase chain
      reaction, a sensitive, quantitative technique allowing analysis of multiple
      cytokines from small tumour samples, was used. RESULTS: Interferon (IFN)-gamma
      was significantly elevated in actively regressing BCCs compared with non
      regressing BCCs. Furthermore, interleukin (IL)-2, tumour necrosis factor (TNF)
      beta and CD3 delta tended to be elevated in actively regressing tumours, although
      not to statistically significant levels. IFN-gamma, IL-2, IL-10, TNF-beta,
      granulocyte-macrophage colony-stimulating factor and Fas ligand showed strong
      positive correlations with CD3 delta, indicating an association between
      infiltrating T cells and these cytokines. CONCLUSIONS: These findings support a
      role for T-helper 1 type cytokines in mediating spontaneous regression of BCCs.

PMID- 10886142
TI  - IgA antineutrophil cytoplasmic antibodies in cutaneous vasculitis.
AB  - BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) of the IgA isotype have,
      for the most part, been detected in patients with Henoch-Schonlein purpura (HSP)
      or inflammatory bowel disease. OBJECTIVES: We have evaluated the prevalence of
      IgA ANCA in a series of patients with different causes of cutaneous vasculitis.
      METHODS: Forty consecutive patients with histologically proven leucocytoclastic
      vasculitis were included in the study: 18 had systemic vasculitis as well as
      cutaneous lesions, 10 of whom were diagnosed as having HSP, and 22 had only
      cutaneous vasculitis (with no identified cause in 10 cases). IgA ANCA were sought
      by indirect immunofluorescence using ethanol-fixed human neutrophil preparations
      as the substrate. RESULTS: IgA ANCA were detected in six of 40 patients (15%)
      (one each with HSP, ulcerative colitis, Sjogren's syndrome,
      hypergammaglobulinaemia associated with Castelman's disease, erythema elevatum
      diutinum and bacterial endocarditis). Three of these patients also had IgG ANCA
      whose target antigen remained unidentified. CONCLUSIONS: IgA ANCA are rarely
      observed in HSP (10%) and can be detected in a wide variety of other cutaneous
      vasculitides.

PMID- 10886143
TI  - The 120-kDa soluble ectodomain of type XVII collagen is recognized by
      autoantibodies in patients with pemphigoid and linear IgA dermatosis.
AB  - BACKGROUND: Type XVII collagen promotes adhesion of basal keratinocytes to
      epidermal basement membrane, and is the target of disease in patients with
      certain inherited or acquired blistering diseases. Two forms of type XVII
      collagen are produced by cultured human keratinocytes: a 180-kDa full-length,
      transmembrane protein, and a recently identified 120-kDa soluble fragment that
      corresponds to its collagenous ectodomain. OBJECTIVES: We aimed to determine the
      incidence and pattern of reactivity of autoantibodies against the 180- and 120
      kDa forms of type XVII collagen in sera from 40 patients with bullous pemphigoid
      (BP), pemphigoid gestationis or cicatricial pemphigoid (CP), as well as six
      patients with linear IgA dermatosis (LAD). METHODS: Various immunochemical
      techniques were used. RESULTS: These studies found that the 120-kDa fragment of
      type XVII collagen was bound by circulating autoantibodies in 13 of 38 patients
      with BP or CP and all six patients with LAD. While many pemphigoid sera had
      specific reactivity against one but not both forms of this protein,
      autoantibodies from patients with LAD bound only the soluble ectodomain.
      CONCLUSIONS: These findings are consistent with the presence of both neoepitopes
      and cross-reactive epitopes on the ectodomain of type XVII collagen. The finding
      that sera from patients with LAD showed specific reactivity to epidermal basement
      membrane suggests that such neoepitopes are present in human skin and that their
      targeting by autoantibodies may contribute to disease pathogenesis.

PMID- 10886144
TI  - Elevated levels of eotaxin and interleukin-5 in blister fluid of bullous
      pemphigoid: correlation with tissue eosinophilia.
AB  - BACKGROUND: Bullous pemphigoid (BP) often provokes blood and tissue eosinophilia,
      which suggests that some chemoattractants modulate the eosinophil infiltration in
      BP. Eotaxin, a CC chemokine, strongly attracts eosinophils, and interleukin (IL)
      5 induces eosinophil differentiation, proliferation and colony formation in
      vitro. OBJECTIVES: To examine the correlation between levels of eotaxin and IL-5
      and the number of lesional eosinophils, and the expression of eotaxin in BP
      lesions. PATIENTS/METHODS: In this study we measured eotaxin and IL-5 levels in
      blister fluid of BP by enzyme-linked immunosorbent assay. We also examined the
      expression of eotaxin in BP lesions by immunohistochemistry. RESULTS: Both
      eotaxin and IL-5 were detected at high levels in BP blister fluid. Blister fluid
      eotaxin, but not IL-5 levels, correlated significantly with the number of dermal
      infiltrating eosinophils. By immunohistochemistry, eotaxin was strongly expressed
      in epidermal keratinocytes around BP blisters. CONCLUSIONS: These findings
      suggest that eotaxin and IL-5 are strongly associated with the tissue
      eosinophilia of BP. Therapies which aim to inhibit production of eotaxin and IL-5
      may improve the inflammation and blister formation in BP.

PMID- 10886145
TI  - An open clinical trial of sulphamethoxypyridazine in the treatment of mucous
      membrane pemphigoid.
AB  - Twenty-five patients with mucous membrane pemphigoid (MMP), whose oral lesions
      were unresponsive to topical steroid treatment, were treated with 1 g daily of
      sulphamethoxypyridazine (SMXP), a long-acting sulphonamide antibiotic, in an open
      prospective clinical trial. Lesion severity was assessed objectively in a
      semiquantitative fashion before treatment and after 14 weeks of treatment. The
      patient's subjective assessment of the associated pain or discomfort, using a
      visual analogue scale, was also recorded at these times. Three patients (12%)
      were withdrawn from the study owing to side-effects or complications, one due to
      an allergic reaction, the other two because of significant haemolysis. For the
      remainder there was a significant improvement in the mean objective clinical
      scores for desquamative gingivitis, other oral lesions, conjunctival
      inflammation, nasal, vulvovaginal and skin involvement, after 14 weeks treatment
      with SMXP (all P < 0.001, except skin P < 0. 01). Only conjunctival scarring
      showed no improvement. In addition, there was a significant improvement (P <
      0.001) in the pain scores for the mouth, eyes, nose, vulvovaginal region and
      skin. The results indicate that with appropriate monitoring SMXP is an effective
      treatment for MMP and compares favourably with other systemic agents used in the
      management of this condition.

PMID- 10886146
TI  - Treatment of erythrodermic cutaneous T-cell lymphoma with intermittent
      chlorambucil and fluocortolone therapy.
AB  - BACKGROUND: Erythrodermic cutaneous T-cell lymphomas (CTCL) including Sezary
      syndrome have been successfully treated with daily administration of chlorambucil
      and prednisone (Winkelmann regimen). OBJECTIVES: Our purpose was to determine the
      efficacy and safety of a low-dose pulse chemotherapy with chlorambucil and
      fluocortolone in this stage of the disease. Fluocortolone has the same potency as
      prednisone but lacks a mineralocorticoid effect. PATIENTS/METHODS: Thirteen
      patients with erythrodermic CTCL (stages III-IVb) were treated with chlorambucil
      and fluocortolone therapy (chlorambucil 10-12 mg day-1 for 3 days and
      fluocortolone, first day 75 mg, second day 50 mg and third day 25 mg) as primary
      therapy in an uncontrolled pilot study. Treatment was started with pulses every 2
      weeks; subsequently, the intervals were prolonged according to the clinical
      status. Clinical outcome, side-effects and long-term survival were assessed.
      RESULTS: Seven patients achieved a complete remission and six had a partial
      response (improved significantly). The mean duration of remissions was 16.5
      (median 12) months. The mean number of cycles necessary during the first year was
      one cycle every 5 weeks. No treatment-related severe side-effects occurred. The
      long-term follow-up (mean 31.5, median 27 months) showed that six patients
      remained in complete remission and three showed a stable partial remission. Four
      patients died, two of them from their lymphoma. CONCLUSIONS: We conclude that
      pulse chemotherapy with chlorambucil and fluocortolone is effective and safe in
      the treatment of erythrodermic CTCL and should be considered as an alternative to
      the classical Winkelmann treatment scheme.

PMID- 10886147
TI  - Longitudinal erythronychia with distal subungual keratosis: onychopapilloma of
      the nail bed and Bowen's disease.
AB  - We biopsied longitudinal erythronychia in 16 subjects, and found an
      onychopapilloma in 14 cases and Bowen's disease in the remaining two. Shared
      clinical features in addition to erythronychia (or sometimes an interrupted line
      made up of splinter haemorrhages) were typically a longitudinal marked ridge of
      the nail bed expanded at the distal nail bed as subungual keratosis, and
      associated localized onycholysis. The presentation of Bowen's disease in this
      pattern has not been previously reported. In all cases of onychopapilloma of the
      nail bed, acanthosis and papillomatosis were evident, and were associated with a
      keratogenous zone identical to the nail matrix. In addition, we found
      multinucleate giant cells in two onychopapillomas. We have therefore suggested
      that the term 'localized, distal, subungual keratosis with multinucleate cells'
      should be replaced by 'onychopapilloma' (nail-producing papilloma).

PMID- 10886148
TI  - Post-kala-azar dermal leishmaniasis in the Sudan: clinical presentation and
      differential diagnosis.
AB  - Post-kala-azar dermal leishmaniasis (PKDL) is a common complication following
      kala-azar (visceral leishmaniasis). In a prospective study in a village in the
      endemic area for kala-azar in the Sudan, 105 of 183 (57%) kala-azar patients
      developed PKDL. There was a significantly higher PKDL rate (69%) in those who
      received inadequate and irregular treatment of kala-azar than in those who were
      treated with stibogluconate 20 mg kg-1 daily for 15 days (35%). The group of
      patients who developed PKDL did not differ from those who did not develop PKDL
      with regard to age and sex distribution, reduction in spleen size, and conversion
      in the leishmanin skin test (LST). In a clinical study, 416 PKDL patients were
      analysed and divided according to grade of severity. Severe PKDL was more
      frequent in younger age groups (P < 0.001); there was an inverse correlation
      between grade and conversion in the LST (P < 0.01). In 16% of patients tested,
      parasites were demonstrated in inguinal lymph node or bone marrow aspirates,
      indicating still visceral disease (para-kala-azar dermal leishmaniasis); there
      was no correlation between the presence of parasites and grade of severity.
      Conversion rates in the LST were lower than in those who did not have
      demonstrable parasites (11% and 37%, respectively; P < 0.01). In the absence of
      reliable and practical diagnostic tests, PKDL may be diagnosed on clinical
      grounds and differentiated from other conditions, of which miliaria rubra was the
      most common. Differentiation from leprosy was most difficult.

PMID- 10886149
TI  - Subcorneal pustular dermatosis type of IgA pemphigus: demonstration of
      autoantibodies to desmocollin-1 and clinical review.
AB  - We describe a 40-year-old Japanese man with a 3-year history of vesiculopustular
      lesions resembling subcorneal pustular dermatosis. Histopathology showed
      subcorneal pustules containing a few acantholytic cells, and direct
      immunofluorescence disclosed IgA deposition in the intercellular space of the
      upper epidermis. Circulating IgA autoantibodies of very low titre were also
      demonstrated by indirect immunofluorescence. A novel cDNA transfection technique
      clearly detected IgA autoantibodies reactive with human desmocollin-1. Combined
      therapy with dapsone and etretinate improved the skin lesions. We review the
      clinical features of 49 patients in the literature who presented with
      vesiculopustular lesions and intraepidermal IgA deposition.

PMID- 10886150
TI  - A paraneoplastic mixed bullous skin disease: breakdown in tolerance to multiple
      epidermal antigens.
AB  - We report a new type of paraneoplastic mixed bullous skin disease in a patient
      with a B-cell lymphoma associated with monoclonal IgM kappa paraproteinaemia. The
      patient's clinical and histological features were reminiscent of bullous
      pemphigoid. Characterization of antiepidermal antibodies by immunoblotting and
      indirect immunoelectron microscopy demonstrated a novel pattern of reactivity:
      IgG antibodies were directed against desmoplakins I-II and BPAG2, and were
      associated with antidesmoglein 3 polyclonal IgM antibodies. Such an autoreactive
      pattern involving antidesmoplakins, anti-BPAG2 and antidesmoglein 3 antibodies
      has not been previously reported. It reflects the breakdown of tolerance to
      multiple epidermal antigens observed in some patients with malignancy.

PMID- 10886151
TI  - Pyoderma gangrenosum in a patient with autoimmune haemolytic anaemia and
      complement deficiency.
AB  - About 50% of cases of pyoderma gangrenosum (PG) are associated with a variety of
      systemic diseases. We describe a patient with severe PG on both legs who suffered
      from an autoimmune haemolytic anaemia in association with a congenital deficiency
      of complement factors C2 and C4. To the best of our knowledge, this constellation
      has not been previously reported.

PMID- 10886152
TI  - Rituximab in cutaneous B-cell lymphoma: a report of two cases.
AB  - We report two patients with primary cutaneous B-cell lymphoma who were treated
      with rituximab, a new anti-CD20 monoclonal antibody. The first patient, who had a
      diffuse large B-cell lymphoma of the lower leg, achieved an 85% improvement. The
      second patient, who had a primary cutaneous B-cell lymphoma, which had undergone
      high-grade transformation and systemic spread, achieved a minor response of
      approximately 30%. Both patients subsequently relapsed. The first patient
      achieved complete clearance with a second course of rituximab given with systemic
      chemotherapy, but again relapsed. Treatment with rituximab has been reported to
      produce response rates of 48% in relapsed systemic low-grade or follicular
      lymphoma, but there are no previous reports of the use of rituximab in primary
      cutaneous B-cell lymphoma.

PMID- 10886153
TI  - Angiotropic lymphoma: proliferation of B cells in the capillaries of cutaneous
      angiomas.
AB  - We report a 52-year-old patient with cutaneous angiomas on the trunk in
      association with angiotropic lymphoma involving the nervous system. The lesional
      skin showed proliferation of atypical B cells in the capillaries. The diagnosis
      of angiotropic lymphoma with neurological deficits is often difficult before
      death. Thus, skin biopsy in this case proved to be diagnostic of the central
      nervous system disease without the risk of brain biopsy. The diagnosis of
      angiotropic lymphoma in the future may be achievable by biopsy of coincidental
      angiomas.

PMID- 10886154
TI  - Multiple cutaneous immunocytoma with secondary anetoderma: a report of two cases.
AB  - We describe two men with multiple erythematous dermal nodules which were
      clinically and histologically consistent with a diagnosis of primary cutaneous
      immunocytoma. Both patients exhibited the very unusual feature of secondary
      anetoderma occurring in spontaneously resolving lesions. There is one previous
      report of anetoderma in association with a plasmacytoma. The pathogenesis remains
      unknown but release of cytokines such as interleukin-6 may be implicated.

PMID- 10886155
TI  - Malignant melanoma and lymphoproliferative malignancy: is there a shared
      aetiology?
AB  - We report seven patients who developed malignant melanoma either coincident with
      or before the diagnosis of non-Hodgkin's lymphoma or chronic lymphatic leukaemia.
      One patient died secondary to leukaemia, and chemotherapy-induced
      immunosuppression may have contributed to the development of metastatic melanoma
      in another patient. Immunosuppression, exposure to ultraviolet radiation and
      genetic factors may result in a host environment that is conducive to the
      development of both tumours in these patients.

PMID- 10886157
TI  - Congenital infiltrating lipoma of the upper limb in a patient with von Willebrand
      disease.
AB  - Infiltrating lipoma is a rare variety of lipoma, characterized by an infiltration
      of the adipose tissue of the muscles. Infiltrating lipomas are usually classified
      in two groups: intermuscular infiltrating lipoma and intramuscular infiltrating
      lipoma. Most are acquired, and they usually appear in middle-aged individuals.
      Exceptionally, they are congenital. In such cases they are not related to other
      diseases. We report an 8-year-old boy with a congenital infiltrating lipoma of
      the upper limb and von Willebrand disease. Both diseases are linked to an
      alteration in chromosome 12, but this clinical association seems to be random
      rather than causal.

PMID- 10886156
TI  - Compound heterozygous group A xeroderma pigmentosum patient with a novel mutation
      and an inherited reciprocal translocation.
AB  - The severity of neurological abnormalities in Japanese group A xeroderma
      pigmentosum (XP-A) patients correlates with the sites of non-sense mutation in
      the XP-A gene. We describe a patient who presented with a more severe
      photosensitivity and neurological abnormality than those in typical Japanese XP-A
      patients with a splicing mutation in intron 3. The patient was compound
      heterozygous for the splicing mutation in intron 3, which resulted in formation
      of a non-sense codon in exon 4, and a novel non-sense mutation at codon 208 in
      exon 5, a C to T transition creating a stop codon TAG. Although the combination
      of these mutations might have been thought to cause only mild neurological signs,
      the longer truncated XP-A proteins than those of typical XP-A patients may have
      resulted in severe neurological symptoms. This phenomenon may be explained by a
      translocation of chromosome (1;10)(q25.3;q22.3) inherited from his father.

PMID- 10886158
TI  - Verrucous carcinoma arising in pseudoepitheliomatous keratotic and micaceous
      balanitis, without evidence of human papillomavirus.
AB  - Pseudoepitheliomatous keratotic and micaceous balanitis (PKMB) is a condition
      which occurs on the glans penis of older men and may be associated with the
      development of a verrucous carcinoma. A role for human papillomavirus (HPV) in
      the aetiology of verrucous carcinoma has been implicated and several different
      HPV types have been found. We report a 74-year-old man who developed a verrucous
      carcinoma within an area of PKMB on the glans penis. Using a broad-spectrum
      polymerase chain reaction technique for identifying HPV, the epidermis of the
      area of PKMB and of the verrucous carcinoma were examined and no HPV DNA was
      identifiable. These results suggest that there is no part for HPV in the
      pathogenesis of PKMB or its transformation to verrucous carcinoma.

PMID- 10886159
TI  - Paracoccidioidomycosis (South American blastomycosis) successfully treated with
      terbinafine: first case report.
AB  - We describe a 63-year-old man who presented with painful malodorous lesions in
      the perianal, perineal and scrotal regions. Following definitive diagnosis of
      paracoccidioidomycosis, he was treated initially with
      trimethoprim/sulphamethoxazole, but there was no clinical improvement. He then
      received terbinafine (Lamisil) 250 mg twice daily for 6 months. There was rapid
      resolution of all lesions and complete relief of symptoms, without any associated
      side-effects. The patient remains clinically well and without any evidence of
      infection 2 years after discontinuation of terbinafine treatment.

PMID- 10886160
TI  - Head actinomycetoma with a double aetiology, caused by Nocardia brasiliensis and
      N. asteroides.
AB  - We describe a 64-year-old man with an actinomycetoma of the frontal region of the
      head caused simultaneously by two aetiological agents, Nocardia brasiliensis and
      N. asteroides. This case is presented due to the unusual body site affected and,
      above all, because two aetiological agents were isolated.

PMID- 10886161
TI  - Simultaneous occurrence of folliculitis decalvans capillitii in identical twins.
AB  - Folliculitis decalvans is a chronic purulent folliculitis resulting in permanent
      hair loss and follicular atrophy. We report 32-year-old identical female twins
      presenting with relapsing pruritic outbreaks on the scalp resulting in areas of
      permanent baldness. Staphylococcus aureus was detected in the lesions of both
      women. Histopathology confirmed the diagnosis of folliculitis decalvans.
      Immunological testing showed no alteration of the immune system. To our
      knowledge, this is the first report on folliculitis decalvans occurring in
      identical twins, suggesting a possible genetic component in this disease.

PMID- 10886163
TI  - Nerve growth factor and its receptor system in psoriasis - reply from author

PMID- 10886162
TI  - Nerve growth factor and its receptor system in psoriasis.

PMID- 10886165
TI  - Efficacy of borage oil in patients with atopic eczema - reply from author

PMID- 10886164
TI  - Efficacy of borage oil in patients with atopic eczema.

PMID- 10886166
TI  - Management of oral lichen planus.

PMID- 10886167
TI  - S100-beta serum protein--a new marker in the diagnosis and monitoring of
      Langerhans cell histiocytosis?

PMID- 10886168
TI  - Staphylococcal septicaemia complicating treatment of atopic dermatitis with
      mycophenolate.

PMID- 10886169
TI  - Methotrexate-induced exacerbation of urticarial vasculitis: an unusual adverse
      reaction.

PMID- 10886170
TI  - Linear IgA disease: successful treatment with cyclosporin.

PMID- 10886171
TI  - 'Microdose' isotretinoin.

PMID- 10886172
TI  - Circumlesional scaling induced by vitamin D--a guide to compliance.

PMID- 10886173
TI  - Wegener's granulomatosis presenting as neutrophilic dermatosis: a case report.

PMID- 10886174
TI  - Chronic graft-vs.-host disease with severe cicatrizing conjunctivitis mimicking
      cicatricial pemphigoid.

PMID- 10886175
TI  - A case of systemic lupus erythematosus associated with cancer of the lung: a
      paraneoplastic association?

PMID- 10886176
TI  - A case of naevus sebaceous associated with familial retinoblastoma, multiple
      lipomata and meningioma.

PMID- 10886177
TI  - Angiolymphoid hyperplasia with eosinophilia: successful treatment with pulsed dye
      laser using the double pulse technique.

PMID- 10886178
TI  - Nodular prurigo successfully treated with the pulsed dye laser.

PMID- 10886179
TI  - Successful treatment of solar lentigines by brief gentle cryosurgery using a
      Kryomed device.

PMID- 10886180
TI  - Synchronous onset of penile lichen sclerosus and vitiligo.

PMID- 10886181
TI  - Actinic damage and squamous cell carcinoma in sun-exposed skin affected by
      vitiligo.

PMID- 10886182
TI  - Delayed onset of cutaneous symptoms in erythropoietic protoporphyria.

PMID- 10886183
TI  - Angioblastoma (Nakagawa) with hyperhidrosis, and relapse after a 10-year
      interval.

PMID- 10886184
TI  - Asymmetric periflexural exanthem in adults.

PMID- 10886185
TI  - Multilocular inoculation tuberculosis of the skin after stay in Africa: detection
      of mycobacterial DNA using polymerase chain reaction.

PMID- 10886186
TI  - Nasolabial follicular sebaceous casts: a novel complication of isotretinoin
      therapy.

PMID- 10886187
TI  - Recurrent bullous dermatitis artefacta mimicking immunobullous disease.

PMID- 10886188
TI  - Acute generalized exanthematous pustulosis induced by ingestion of lacquer
      chicken.

PMID- 10886189
TI  - Papulonecrotic tuberculide in a human immunodeficiency virus type 1-seropositive
      patient.

PMID- 10886190
TI  - Images in haematology: skin involvement in adult T-cell leukaemia.

PMID- 10886191
TI  - Historical review of lymphomas.

PMID- 10886192
TI  - Current status of antiangiogenic factors.

PMID- 10886193
TI  - Management of Kostmann syndrome in the G-CSF era.

PMID- 10886194
TI  - Management of thrombotic thrombocytopenic purpura.

PMID- 10886195
TI  - The multigenic basis for venous thrombosis.

PMID- 10886196
TI  - Recombinant fragment of von Willebrand factor AR545C inhibits platelet binding to
      thrombin and platelet adhesion to thrombin-treated endothelial cells.
AB  - Activated, but not resting, platelets are capable of adhering to intact
      endothelial cells (ECs). We evaluated the effect of a recombinant von Willebrand
      factor (VWF) fragment AR545C, which inhibits glycoprotein Ib (GPIb)/VWF binding,
      on platelet adhesion to human ECs under static or flow conditions. Incubation of
      resting platelets with intact endothelium under flow conditions (350/s) resulted
      in minimal platelet adhesion. The adhesion was enhanced two- to threefold after
      either platelet activation by thrombin receptor agonist peptide (TRAP) or EC
      pretreatment with thrombin. The enhancing effect of thrombin was abolished by
      addition of either hirudin (10 u/ml) or PGE1 (1 microg/ml). Preincubation of
      resting platelets with increasing concentrations of AR545C under static or flow
      conditions resulted in a dose-dependent inhibition of thrombin-induced enhanced
      adhesion to ECs. AR545C (0.3 microM) completely abolished the effect of thrombin,
      reducing platelet adhesion to the control level observed with non-treated ECs. In
      contrast, the same concentration of AR545C had no effect on the adhesion of TRAP
      activated platelets to ECs. AR545C also inhibited thrombin-induced platelet
      aggregation and binding in a dose-dependent manner. In addition, 0.3 microM of
      AR545C reduced thrombin-induced serotonin release by 57%, whereas monoclonal
      antibody AN51, which inhibits ristocetin-induced platelet aggregation, had no
      effect on either thrombin-induced platelet aggregation or binding or on serotonin
      release. Similarly, AR545C had no effect on TRAP-induced serotonin release. These
      findings suggest that (i) AR545C inhibits platelet activation mediated by
      thrombin and this inhibition occurs through blocking the high-affinity thrombin
      binding sites on the GPIb/IX complex and (ii) AR545C has no effect on the
      moderate affinity thrombin receptor (seven transmembrane domain thrombin
      receptor; STDR).

PMID- 10886197
TI  - Heritability of elevated factor VIII antigen levels in factor V Leiden families
      with thrombophilia.
AB  - Factor VIII activity (factor VIII:C) and factor VIII antigen (factor VIII:Ag)
      levels above 150 IU/dl are associated with a five- to sixfold increased risk of
      venous thrombosis compared with levels < 100 IU/dl. These high levels are present
      in 25% of patients with a first episode of deep-vein thrombosis and in 11% of
      healthy controls. von Willebrand factor (VWF) and blood group are important
      determinants of the factor VIII level in plasma and therefore contribute to
      thrombotic risk, while factor VIII appears to be the final effector. Previously,
      we found familial clustering of factor VIII:C levels in women, which remained
      after adjustment for VWF and blood group. In the present study, we analysed the
      familial influence on factor VIII:Ag levels exceeding 150 IU/dl in 12 large
      families with thrombophilia in which high factor VIII:Ag levels contribute to
      thrombotic risk. As expected, blood group was a main determinant of the plasma
      factor VIII level: 58 relatives (32%) had factor VIII levels above 150 IU/dl and
      50 (86%) of these had blood group non-O. After adjustment for blood group and
      age, we found an association between factor VIII:Ag levels in sister pairs (0.35,
      P = 0.003), brother pairs (0.35, P = 0.003), brother-sister pairs (0.35, P <
      0.001) and in mother-son pairs (0.45, P = 0.02), but not in father-daughter or
      father-son pairs. The familial aggregation test was strongly positive for factor
      VIII:Ag levels (P < 0.001) and remained so after adjustment for the influence of
      blood group. We conclude that high factor VIII:Ag levels are a highly prevalent
      risk factor for venous thrombosis and contribute to risk in families with
      thrombophilia, and that these high levels are likely to be genetically determined
      by factors other than just blood group.

PMID- 10886198
TI  - Assay discrepancy in mild haemophilia A due to a factor VIII missense mutation
      (Asn694Ile) in a large Danish family.
AB  - Factor VIII gene analysis in a large consanguinous Danish family comprising 24
      affected males and four homozygously affected females revealed an Asn694Ile
      mutation within the A2 domain. The factor VIII gene mutation led to a mild
      haemophilia A phenotype with factor VIII function displaying discordance between
      one-stage clotting and chromogenic two-stage assays. In one-stage assays, values
      ranged from 0.05 to 0.30 IU/ml (males) and from 0.19 to 0.29 IU/ml (homozygous
      affected females), whereas the chromogenic two-stage assay produced values of
      around only 50% of the one-stage result [0. 02-0.12 IU/ml (males); 0.06-0.10
      IU/ml (females)]. The differences are suggested to be caused by the effect of the
      mutation on the active cleaved form of the factor (F)VIII protein. As the
      original amino acid (Asn) is conserved in all known FVIII A2 sequences, but not
      in ceruloplasmin, we suggest that Asn694 is involved in an A2-specific functional
      role. Examination of a homology model of the A domains predicts that the
      Asn694Ile mutation (i) results in the loss of two potential hydrogen-bonding
      interactions and (ii) hampers the integration of the bulky side-chain of Ile into
      the A2 domain core, probably causing an altered stability and/or folding of the
      protein. Interestingly, the disease in this Danish family was originally proposed
      to be von Willebrand-Jurgens disease. However, the current study rules out the co
      existence of either von Willebrand's disease or the presence of the Normandy
      variant of von Willebrand factor (type 2N).

PMID- 10886199
TI  - Lymphocyte subset abnormalities in multitransfused HIV-negative haemophilia A
      patients are not due to chronic hepatitis C virus infection.
AB  - Several abnormalities of immune parameters have been described in HIV-negative
      haemophiliacs, including changes in numbers of T4 and T8 cells, T4/T8 ratio and
      numbers of activated T cells. To assess the contribution of hepatitis C to these
      abnormalities, we compared lymphocyte subsets in 20 HIV-negative HCV-positive
      haemophilia A patients and in 14 non-haemophiliacs with chronic hepatitis C with
      those in 18 healthy controls. In haemophilia patients, higher numbers of T
      lymphocytes and activated T8 cells, lower numbers of B lymphocytes and a normal
      T4/T8 ratio were seen. These differences were either not demonstrated in
      hepatitis C controls or were less pronounced and in the opposite direction. We
      conclude that haemophilia A patients showed abnormalities in lymphocyte subsets
      that could not be attributed to chronic hepatitis C.

PMID- 10886200
TI  - Thrombopoietin in Plasmodium falciparum malaria.
AB  - Thrombopoietin (TPO) is the key growth factor for platelet production and is
      elevated in states of platelet depletion. As thrombocytopenia is a common finding
      in malaria, we analysed TPO regulation before, during and after antimalarial
      treatment. Before treatment, TPO serum levels were significantly higher in
      patients with severe malaria (n = 35) than in patients with uncomplicated malaria
      (n = 44; P = 0.024), normalizing within 14-21 d of therapy. The rapid
      normalization of TPO levels and increase in low peripheral platelet counts after
      treatment indicate that the biosynthesis of TPO and its regulation in malaria
      patients are normal.

PMID- 10886201
TI  - A prospective randomized study to determine the optimal dose of intravenous
      vitamin K in reversal of over-warfarinization.
AB  - The optimal management of asymptomatic overanticoagulated patients remains
      unknown. We measured international normalized ratio (INR), activated partial
      thromboplastin time (APTT) and prothrombin fragment 1 + 2 (F1 + 2) over 7 d in 24
      asymptomatic or mildly haemorrhagic patients on warfarin with prolonged INR of >
      7.0 who were randomized to receive 0.5 mg, 1 mg or 2 mg intravenous vitamin K. Of
      six severely overanticoagulated patients (INR > 9.5 with APTT ratio > 2), five
      failed to achieve an INR < or = 4.0 on day 1, irrespective of vitamin K dose
      given. In the remaining 18 cases, an optimal response (INR 2-4 at day 1) was
      observed in 67% of those receiving 0.5 mg vitamin K, but only in 33% of those
      receiving 1 or 2 mg, the majority of whom developed an INR < 2.0. Our results
      support an optimal dose of 0.5 mg i.v. vitamin K for most overanticoagulated
      patients, with possibly a repeat dose in the small group of severely
      overanticoagulated patients.

PMID- 10886202
TI  - Clonal Th2 lymphocytes in patients with the idiopathic hypereosinophilic
      syndrome.
AB  - Idiopathic hypereosinophilic syndrome (HES) and Gleich's syndrome are related
      disorders characterized by persistent or recurrent hypereosinophilia of unknown
      origin. Elevated IgE levels and polyclonal hypergammaglobulinaemia are considered
      as markers of benign outcome in this setting as they are generally associated
      with predominant cutaneous manifestations and favourable response to
      glucocorticoid therapy. In a previous study, we identified a clonal population of
      CD3-CD4+ Th2-like lymphocytes secreting interleukin (IL)-5 and IL-4 in peripheral
      blood of a patient fulfilling the diagnostic criteria of HES with associated
      serum hyper-IgE. We now extend this observation by describing identical findings
      in three additional patients, and we compare their clinical and biological
      parameters with five other patients with HES. Chromosomal abnormalities were
      detected in purified CD3-CD4+ Th2 cells from three patients, among whom one
      developed anaplastic null cell lymphoma. We therefore suggest that a careful
      search for T-lymphocyte clonality and cytogenetic changes should be included in
      the work-up of HES for adequate management.

PMID- 10886203
TI  - In vitro and in vivo studies with human carrier erythrocytes loaded with
      polyethylene glycol-conjugated and native adenosine deaminase.
AB  - Polyethylene glycol-conjugated adenosine deaminase (pegademase) is used for
      enzyme replacement therapy for patients with severe combined immunodeficiency
      caused by adenosine deaminase deficiency. The entrapment of pegademase within
      human energy-replete carrier erythrocytes using a hypo-osmotic dialysis procedure
      was investigated with the objective of prolonging the in vivo circulatory half
      life of the enzyme and maintaining therapeutic blood levels. Native unmodified
      adenosine deaminase (ADA) was similarly studied. The efficiency of pegademase
      entrapment was low (9%) whereas the entrapment of native unmodified ADA was
      substantial (50%), suggesting that the polyethylene glycol side-chains were
      impeding intracellular entrapment. The biochemical characteristics and the
      osmotic fragility of these carrier erythrocytes were not adversely affected by
      the entrapment of either pegademase or native ADA. In vivo survival studies of
      pegademase-loaded 51Cr-labelled carrier erythrocytes in an ADA-deficient adult
      patient showed a mean cell half-life of 16 d. Carrier erythrocyte-entrapped
      pegademase and native ADA had in vivo half-lives of 20 and 12.5 d, respectively,
      demonstrating that entrapment prolongs the half-life over that of plasma
      pegademase, which has a circulating half-life of 3-6 d. These results provide the
      basis for a more extensive clinical evaluation of carrier erythrocyte-entrapped
      native adenosine deaminase therapy.

PMID- 10886204
TI  - Insulin and insulin-like growth factor I support the proliferation of erythroid
      progenitor cells in bone marrow through the sharing of receptors.
AB  - The effects of insulin and insulin-like growth factor I (IGF-I) on the
      proliferation of erythroid progenitor cells in bone marrow were studied in serum
      deprived culture. Primitive human bone marrow cells were purified by cell sorting
      on the basis of the expression of CD34 and the Kit receptor. Insulin and IGF-I
      with erythropoietin (EPO) dose dependently supported the formation of erythroid
      colonies of CD34+/Kit+ cells in bone marrow. The direct effect of insulin and IGF
      I on the stimulation of primitive erythroid progenitor cells was confirmed by
      single-cell proliferation studies in serum-deprived liquid suspension culture.
      The addition of insulin and/or IGF-I to stem cell factor (SCF) resulted in an
      additive increase in the number of erythroid colonies. The erythroid colonies
      formed by insulin and IGF-I with EPO were different in size from those formed by
      SCF with EPO. These findings imply that erythroid progenitor cells responding to
      insulin and IGF-I might be at a different developmental stage of erythropoiesis
      from those responding to SCF in CD34+/Kit+ cells. Similarly, insulin and IGF-I
      with EPO supported the proliferation of the mature erythroid progenitor cells in
      light-density bone marrow mononuclear cells (LDBMCs). The addition of the anti
      receptor antibody to IGF-I receptor or insulin receptor partially suppressed
      erythroid colony formation supported with insulin or IGF-I in both CD34+/Kit+
      cells and LDBMCs. The simultaneous addition of both receptor antibodies
      completely abrogated the erythroid colony formation. These results suggest that
      insulin and IGF-I directly stimulate the proliferation of the late stage of
      primitive erythroid progenitor cells and mature erythroid progenitor cells
      through the sharing of receptors.

PMID- 10886205
TI  - Captopril inhibits in vitro and in vivo the proliferation of primitive
      haematopoietic cells induced into cell cycle by cytotoxic drug administration or
      irradiation but has no effect on myeloid leukaemia cell proliferation.
AB  - Angiotensin I-converting enzyme (ACE) has been shown to be involved in the
      catabolism of the tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP). As AcSDKP is a
      physiological inhibitor of haematopoietic stem cell proliferation, we
      investigated the in vitro and in vivo effects of captopril, one of the specific
      inhibitors of ACE, on the proliferation of primitive haematopoietic cells.
      Regenerating bone marrow cells obtained from mice given one injection of cytosine
      arabinoside (100 mg/kg) as well as SA2 myeloid leukaemia cells were incubated in
      vitro for 24 h with 10-6 M captopril. Captopril significantly reduced the
      proportion of high proliferative potential colony-forming cells (HPP-CFC-1) in S
      phase, whereas it had no effect on the proportion of SA2 leukaemic colony-forming
      cells in S-phase. When given in vivo to mice 1 h after 2 Gy gamma-irradiation or
      cytosine arabinoside (AraC) injection, captopril (100 mg/kg) was shown to prevent
      HPP-CFC-1 entry into S-phase induced by these cytotoxic treatments. The observed
      effects correlated with a reduction in ACE degradative activity and an increase
      in the level of endogenous AcSDKP both in the supernatants of captopril-treated
      bone marrow cells and in plasma of treated animals. The present findings suggest
      that AcSDKP might mediate the observed in vitro and in vivo inhibitory effects of
      captopril on primitive haematopoietic cell proliferation.

PMID- 10886206
TI  - CCNU (lomustine), idarubicin and dexamethasone (CIDEX): an effective oral regimen
      for the treatment of refractory or relapsed myeloma.
AB  - We report the results of a non-randomized pilot study of an oral regimen
      comprising CCNU (lomustine; 25 or 50 mg/m2 on day 1), idarubicin (4
      demethoxydaunorubicin) (10 mg/m2 on days 1-3) and dexamethasone (10 mg b.d. on
      days 1-4) in patients with relapsed or refractory myeloma. Treatment was given
      every 28 d for a maximum of six courses. Sixty patients were entered of whom 57
      were evaluable. Overall response rate (partial or minor response) was 49% with
      30% of patients achieving a partial response (50% tumour reduction). Response
      rates were higher in patients with untested relapse than in those with refractory
      disease (overall response rates 56% vs. 31%). The major toxicity was neutropenia
      and the regimen was otherwise well tolerated. The median survival from entry of
      all patients was 15 months, with 30% of patients alive at 2 years. This regimen
      represents a useful addition to available treatment options.

PMID- 10886207
TI  - Induction of apoptosis by vitamin D3 analogue EB1089 in NCI-H929 myeloma cells
      via activation of caspase 3 and p38 MAP kinase.
AB  - EB1089, a novel 1,25-dihydroxyvitamin D3 analogue, has been known to have potent
      antiproliferative properties in a variety of malignant cells both in vitro and in
      vivo. In the present study, we analysed the effect of EB1089 on NCI-H929 human
      myeloma cells. EB1089 inhibited cell growth of NCI-H929 and efficiently induced
      the G1 phase arrest of the cell cycle in a dose-dependent manner. We could also
      detect apoptosis in NCI-H929 cells exposed to EB1089 (1 x 10-7 M for 72 h) using
      the sub-G1 group of the cell cycle by FACS and annexin V binding assays.
      Induction of apoptosis by EB1089 was associated with down-regulation of the Bcl-2
      protein without change of the Bax protein. Regarding caspase activity, which
      plays a crucial role in apoptosis, EB1089-treated NCI-H929 cells revealed an
      increased activity of caspase 3 protease accompanied by degradation of the PARP
      protein in a dose- and time-dependent manner. In addition, EB1089 caused the down
      regulation of p44 extracellular signal-related kinase (ERK) activity and up
      regulation of the p38 kinase activity during apoptosis of NCI-H929 cells. These
      results suggest that EB1089 inhibits growth of NCI-H929 cells via G1 cell cycle
      arrest as well as apoptosis by activating p38 kinase and suppressing ERK
      activity.

PMID- 10886208
TI  - Anaplastic large-cell lymphomas of B-cell phenotype are anaplastic lymphoma
      kinase (ALK) negative and belong to the spectrum of diffuse large B-cell
      lymphomas.
AB  - There is controversy in the literature as to whether anaplastic large-cell
      lymphoma of B-cell phenotype is related to the t(2;5)-positive T- or 'null' cell
      lymphoma of the same morphology. We report a study of 24 lymphomas with
      morphological features of anaplastic large-cell lymphoma which expressed one or
      more B-cell markers and lacked T-lineage markers. Clinical features were more in
      keeping with large B-cell lymphoma than with classical t(2;5)-positive anaplastic
      large-cell lymphoma, and immunostaining for anaplastic lymphoma kinase (ALK)
      protein provided no evidence for the (2;5) translocation (or one of its
      variants). The staining patterns for CD20 and CD79 were typical of diffuse large
      B-cell lymphoma, CD30 expression was variable, and most cases (15/22) lacked
      epithelial membrane antigen (EMA). These findings support the view that 'B-cell
      anaplastic large-cell lymphoma' is unrelated to t(2;5)-positive (ALK-positive)
      lymphoma, and that it represents a morphological pattern occasionally encountered
      among diffuse large B-cell lymphomas. By the same reasoning, most tumours
      diagnosed as 'ALK-negative anaplastic large-cell lymphoma of T-cell or null
      phenotype' probably belong to the spectrum of peripheral T-cell lymphomas.

PMID- 10886209
TI  - Expression of T-cell-associated antigens in B-cell non-Hodgkin's lymphoma.
AB  - We performed the immunophenotyping of 101 patients with B-cell non-Hodgkin's
      lymphoma (B-NHL) using two-colour flow cytometry (FCM) and found that lymphoma
      cells coexpressed at least one kind of T-cell-associated antigen (T-Ag; CD2, CD5,
      CD7) in 25 patients (24. 8%). Among these three T-Ags, CD5 was the most
      frequently expressed, in 21 patients (20.8%), followed by CD7, expressed in five
      patients (5.0%), and CD2, which was expressed in two patients (2.0%). Two kinds
      of T-Ag were simultaneusly expressed in three patients (CD2/CD5, CD2/CD7, and
      CD5/CD7, each expressed in one patient). Concerning the expression pattern of T
      Ag, there were no significant differences between lymph nodes and extranodal
      organs in the three patients with T-Ag-positive B-NHL (T-Ag(+) B-NHL) who were
      analysed. When comparing the clinical features between T-Ag(+) B-NHL and T-Ag
      negative B-NHL (T-Ag(-) B-NHL), extranodal involvement and higher International
      Prognostic Index (H and H.I.) were significantly frequent in the former subgroup
      (P = 0.0119 and P = 0. 0302 respectively).

PMID- 10886210
TI  - Essential role for T cells in human B-cell lymphoproliferative disease
      development in severe combined immunodeficient mice.
AB  - Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disease (BLPD)-like
      lesions develop in severe combined immunodeficient (SCID) mice inoculated with
      peripheral blood mononuclear cells (PBMCs) from EBV-seropositive donors. We used
      this model to investigate the pathogenesis of EBV-associated BLPD. Tumour
      incidence fell from 81% to 11% when only B cells were inoculated, suggesting a
      key role for T cells in tumour formation. This was further underlined by the
      reduction in tumour incidence from 76% to 7% when PBMCs were depleted of CD4
      positive (+ve) helper T cells. Tumour outgrowth was also reduced when PBMC were
      depleted of CD8 +ve, CD45RA +ve or CD45RO +ve T cells. The majority of PBMC
      derived tumours analysed by reverse transcriptase-polymerase chain reaction (RT
      PCR) expressed mRNA for interleukin (IL) 2, 4, 6, 10 and interferon (IFN) gamma.
      This is the cytokine pattern seen in activated T cells and includes B-cell growth
      factors. In situ hybridization studies confirmed that the tumour cells themselves
      express the growth factors, which is consistent with autocrine-stimulated tumour
      growth. Our results suggest the following sequence of events: (1) T cells are
      essential for the initial outgrowth of tumorigenic EBV +ve B cells in vivo; (2)
      the neoplasm sustains its growth in an autocrine, cytokine-stimulated manner; and
      (3) established tumours become independent of T-cell help.

PMID- 10886211
TI  - Screening for mutations of Bcl10 in leukaemia.
AB  - The Bcl10 gene was identified through characterization of the t(1;14)(p22;q32)
      associated with mucosa-associated lymphoid tissue (MALT) lymphoma. Bcl10 is
      implicated in the regulation of apoptosis and has been reported to be mutated in
      other subtypes of non-Hodgkin's B-cell lymphoma (B-NHL) and leukaemic cell lines,
      raising the possibility that its deregulation could be implicated in other forms
      of haematological malignancy. We screened 226 cases, including 123 acute myeloid
      leukaemia (AML), 50 acute lymphoblastic leukaemia (ALL), 20 chronic myeloid
      leukaemia (CML), 10 chronic lymphocytic leukaemia-prolymphocytic leukaemia
      (CLL/PLL) and 23 cases with 1p abnormalities, for Bcl10 mutations by reverse
      transcription polymerase chain reaction-single-stranded conformation polymorphism
      (RT-PCR/SSCP). Three known polymorphisms and two common splice variants were
      identified; however, no mutations were detected. One splice variant led to a 33
      bp in frame deletion, whereas the other caused a 16-bp deletion predicting C
      terminal truncation of Bcl10. However, both splice variants were also detected in
      normal bone marrow, suggesting that they are unlikely to be of pathogenetic
      significance. Furthermore, Southern blot analysis revealed no rearrangements of
      Bcl10 among 16 ALL and 11 cases of haematological malignancy with 1p
      abnormalities. Our results suggest that mutation of the Bcl10 gene as a mechanism
      of tumorigenesis is not associated with leukaemia.

PMID- 10886212
TI  - b3a2 BCR-ABL fusion peptides as targets for cytotoxic T cells in chronic myeloid
      leukaemia.
AB  - Peptide sequences spanning the BCR-ABL protein junction potentially constitute
      novel leukaemia-specific antigens. 9-mer b3a2 fusion peptides have been reported
      to bind with high affinity to HLA-A3, -A11 and -B8. We have studied the effect of
      b3a2 BCR-ABL junctional peptides on the cytotoxic T-cell (CTL) response against
      normal and chronic myeloid leukaemia (CML) cells. Antigen-presenting cells (APCs)
      were prepared from HLA-A3- or -B8-positive peripheral blood mononuclear cells
      (PBMCs) by incubation with phytohaemagglutinin (PHA) and interleukin (IL)-2 for 7
      d. These APCs were pulsed with the respective b3a2 junctional peptide in the
      presence of beta2-microglobulin and were then used to challenge autologous PBMCs
      at 7-d intervals in the presence of IL-2, IL-6, IL-7 and IL-12. On subsequent
      exposure to target cells (either further pulsed normal APCs or unpulsed CML
      cells), specific HLA-restricted CTL responses were observed against all HLA-A3/
      B8 matched normal target cells tested, but not to targets that were HLA
      mismatched. Cytotoxicity was also induced against HLA-A3/-B8 unpulsed CML cells,
      but not against unmatched CML cells. These data indicate (i) that endogenous BCR
      ABL junctional peptides may be presented by CML cells and (ii) that exogenous
      peptides are potential stimulators of autologous antileukaemic CTLs.

PMID- 10886213
TI  - Monitoring of minimal residual disease in patients with MLL-AF6-positive acute
      myeloid leukaemia by reverse transcriptase polymerase chain reaction.
AB  - We studied 210 unselected patients with acute myeloid leukaemia (AML) for MLL
      abnormalities. Twenty-seven patients (13%) with rearranged MLL genes were
      identified by means of Southern blot analysis. An MLL-AF6 fusion transcript was
      detected in six patients by a reverse transcriptase polymerase chain reaction (RT
      PCR) for the MLL-AF6 translocation. Sequence analysis showed fusion of MLL exon 7
      as well as exon 6 (two patients) or MLL exon 6 as well as exon 5 (four patients)
      to AF6 exon 2. In only three patients could the t(6;11) also be identified by
      cytogenetic and/or fluorescence in situ hybridization (FISH) analysis. The MLL
      AF6-positive patients were monitored by RT-PCR for a period of 6-33 months.
      Complete haematological remission (CR) was achieved in all six cases, but was
      short in 5/6 patients (range 2.6-8.3 months). In these five patients, the MLL-AF6
      transcripts were detected in every sample tested after induction and
      consolidation chemotherapy. One patient received autologous bone marrow
      transplantation (BMT) which also did not lead to PCR negativity. Intensive
      salvage therapy was unable to induce a second remission in the relapsed patients.
      One of the six MLL-AF6-positive patients achieved a molecular CR. He is still in
      CR at 33 months after diagnosis. Survival analysis indicates a poor prognosis in
      MLL-AF6-positive patients. The median event-free survival was 6.8 months, the
      median overall survival 15 months. Persistent PCR positivity was consistently
      associated with relapse. Thus, RT-PCR provides a valuable and sensitive tool for
      the identification of t(6;11)-positive AML and the monitoring of response to
      treatment in these patients. The results of RT-PCR may be useful to evaluate
      therapeutic procedures and to make treatment decisions, which will enable
      molecular remissions to be achieved and improve the clinical outcome in this
      group of patients.

PMID- 10886214
TI  - Methotrexate resistance in relapsed childhood acute lymphoblastic leukaemia.
AB  - Treatment failure in childhood acute lymphoblastic leukaemia (ALL) might be
      associated with methotrexate (MTX) resistance. Little is known about MTX
      resistance in relapsed ALL. In this study, we determined ex vivo MTX resistance
      in precursor-B ALL at relapse (rALL) and determined possible defects in MTX
      membrane transport and polyglutamylation. Using the in situ thymidylate synthase
      inhibition assay, 21 rALL samples were threefold more MTX resistant than 63
      initial precursor-B ALL samples, both after short-term and after continuous MTX
      exposure (P < or = 0.01). [3H]-MTX membrane transport did not differ between
      eight rALL and 25 precursor-B ALL samples. Incubation for 24 h with 1 microM [3H]
      MTX resulted in a trend towards a lower accumulation of MTX in 20 relapsed than
      in 83 initial samples of precursor-B ALL samples (906 vs. 1364 pmol/109 cells; P
      = 0.07). Accumulation of long-chain MTX polyglutamates (MTX-Glu4-6) did not
      differ between relapsed and newly diagnosed samples (746 and 889 pmol/109 cells;
      P = 0.1). Activities of the enzymes involved in polyglutamylation
      (folylpolyglutamate synthetase and folylpolyglutamate hydrolase) did not differ
      between rALL and untreated c/pre-B-ALL. This study demonstrates that leukaemic
      cells of children with relapsed precursor-B ALL are relatively MTX resistant, but
      that this MTX resistance is not associated with major impairments in MTX uptake
      or polyglutamylation.

PMID- 10886215
TI  - A novel BCR-ABL transcript (e8a2) with the insertion of an inverted sequence of
      ABL intron 1b in a patient with Philadelphia-positive chronic myeloid leukaemia.
AB  - An atypical BCR-ABL transcript in a patient with Philadelphia (Ph)-positive
      chronic myeloid leukaemia (CML) was detected using a long polymerase chain
      reaction technique. Sequence analysis revealed a joining of BCR exon e8 and ABL
      exon a2, with a 55-base pair (bp) insert of an inverted sequence of ABL intron 1b
      between them, giving rise to an in frame e8a2 BCR-ABL transcript. This is the
      first report of a BCR-ABL transcript with the insertion of an inverted sequence.
      The long PCR technique is a useful screen for atypical BCR-ABL transcripts not
      detected by standard techniques.

PMID- 10886216
TI  - Detection of prognostic significant translocations in childhood acute
      lymphoblastic leukaemia by one-step multiplex reverse transcription polymerase
      chain reaction.
AB  - The search for chromosomal translocations in de novo cases of childhood acute
      lymphoblastic leukaemia (ALL) is crucial for the selection of the appropriate
      therapeutic protocol. In this work, we describe a new method - one-step multiplex
      reverse transcription polymerase chain reaction (RT-PCR) - to screen for
      prognostic significant translocations in childhood ALL. Our approach involves a
      single PCR reaction for the simultaneous detection of the molecular
      rearrangements resulting from the t(9;22), t(12;21), t(4;11) and t(1;19), with a
      turnaround time of less than 24 h. This assay proved to be highly sensitive,
      specific, reproducible and easy to implement in a routine genetics laboratory.

PMID- 10886217
TI  - Fatal cold anti-i autoimmune haemolytic anaemia complicating hairy cell
      leukaemia.
AB  - Hairy cell leukaemia (HCL) is a rare lymphoproliferative disorder associated with
      pancytopenia, splenomegaly and the presence of typical hairy B lymphocytes in the
      bone marrow and/or peripheral blood. The most significant complication relates to
      opportunistic infections that arise as a consequence of neutropenia and
      monocytopenia. HCL is occasionally associated with systemic autoimmune disorders
      including polyarteritis nodosa and rheumatoid disease. Secondary autoimmune
      haemolytic anaemia (AIHA) appears to be rare. We report on two cases of HCL
      complicated by fatal cold anti-i AIHA. Fulminant haemolysis causing death is rare
      in cold AIHA and only a few individual cases have been reported, none having anti
      i specificity.

PMID- 10886218
TI  - Efficient depletion of alloreactive donor T lymphocytes based on expression of
      two activation-induced antigens (CD25 and CD69).
AB  - T lymphocytes play an important role in allogeneic bone marrow/stem cell
      transplantation by supporting engraftment and immune recovery. Moreover, donor T
      cells have been shown to mediate the so-called graft-versus-leukaemia effect and
      are, therefore, increasingly used for adoptive immunotherapy. However, T-cell
      infusions are associated with the risk of a graft-versus-host reaction, which may
      lead to a life-threatening disease. To overcome this problem, we followed a new
      strategy for the exclusive depletion of alloreactive cells. We activated
      allogeneic T cells by cultivation on an adherent cell layer derived from
      peripheral blood. We then depleted activated cells based on the expression of
      CD25, CD69 or both activation-induced antigens using magnetic cell sorting. Mixed
      lymphocyte culture (MLC) reactions and helper T-lymphocyte precursor cell
      frequency (HTLP-f) assays demonstrated that this technique led to a significant
      decrease in alloreactivity of 'donor' cells, which at the same time preserved
      reactivity against third-party cells. The lowest level of alloreactivity was
      found when CD25 and CD69 antibodies were used together for depletion. This
      corresponds with our observation that expression of CD25 or CD69 may partially
      represent different activation pathways. We conclude that ex vivo depletion of
      CD25- and CD69-expressing alloreactive cells may help to overcome limitations of
      adoptive immunotherapy.

PMID- 10886219
TI  - Elevated interleukin (IL)-18 levels during acute graft-versus-host disease after
      allogeneic bone marrow transplantation.
AB  - Acute graft-versus-host disease (aGVHD) after allogeneic bone marrow
      transplantation (BMT) is mediated by grafted T lymphocytes after their
      polarization into type 1 T cells. Interleukin (IL)-18, a novel immunoregulatory
      cytokine, strongly stimulates type 1 T cells, therefore we postulated that IL-18
      may be involved in the pathogenesis of aGVHD. Using an enzyme-linked
      immunosorbent assay (ELISA), we serially measured serum levels of IL-18 in 37
      patients with haematological malignancy before and after allogeneic BMT. Patients
      with aGVHD had high levels of IL-18 that strongly correlated with the severity of
      aGVHD. We also found that they showed reduced serum levels of IL-18 after
      appropriate treatment or at a state of resolution. IL-18 levels were not affected
      by the pretransplant regimen, engraftment or bacterial infection. Compared with
      circulating interferon (IFN)-gamma or IL-12 levels, serum levels of IL-18 showed
      a more sensitive and specific correlation with the disease status of aGVHD. These
      findings suggest that IL-18 may play important roles in the pathogenesis of aGVHD
      and that measurement of serum IL-18 levels can be useful indicator of aGVHD.

PMID- 10886220
TI  - Allogeneic peripheral stem cell transplantation in a case of hereditary
      sideroblastic anaemia.
AB  - We report on a case of pyridoxine refractory hereditary sideroblastic anaemia
      (HSA) in a 19-year-old man who underwent peripheral blood stem cell
      transplantation (PBSCT) from his HLA-identical brother. By using short tandem
      repeat polymorphism, 100% donor cells were observed in peripheral blood on day
      +21; bone marrow showed mixed chimaerism from day +21 to day +221, when 100%
      cells of donor origin were observed. The patient developed extensive chronic
      graft-versus-host disease with favourable response to treatment. When the
      haemoglobin range was normal, a programme of phlebotomies reduced serum ferritin
      levels. Three years after transplantation, the patient has an ECOG rating of 0,
      with completely normal haemoglobin values (15 g/dl). To our knowledge, this is
      the first PBSCT reported in a case of hereditary sideroblastic anaemia.

PMID- 10886221
TI  - A combination of anti-interleukin 6 murine monoclonal antibody with dexamethasone
      and high-dose melphalan induces high complete response rates in advanced multiple
      myeloma.
AB  - To improve the complete response (CR) rate in advanced multiple myeloma (MM)
      without increasing the toxicity of high-dose therapy, we have used a new
      conditioning regimen. A combination of BE-8 [an anti-interleukin 6 (IL-6) murine
      monoclonal antibody] and dexamethasone followed by high-dose melphalan (220
      mg/m2) and autologous stem cell transplantation was used to treat a series of 16
      patients with advanced multiple myeloma. A strong inhibition of IL-6 activity
      evaluated by quantification of C-reactive protein was observed in all patients
      and was correlated with the high CR rate achieved with this combination therapy.

PMID- 10886222
TI  - Coagulation factor content of cryoprecipitate prepared from methylene blue plus
      light virus-inactivated plasma.
AB  - Levels of factor VIII (FVIII) and fibrinogen were assessed in control
      cryoprecipitate and cryoprecipitate prepared in two centres from plasma subjected
      to methylene blue (MB) photochemical virus inactivation. The level of coagulation
      FVIII activity was reduced in plasma by approximately 30% after MB
      photoinactivation, with only 44% (centre A) and 31% (centre B) of units meeting
      the current UK specification of 0.7 iu/ml. A revised specification of 0.5 iu/ml
      is suggested. Losses of less than 11% were seen for von Willebrand factor (VWF)
      related activities. Cryoprecipitate prepared from group O or group A MB-treated
      plasma contained 27-40% less FVIII than control units. This reflected the lower
      levels in MB-treated plasma. The concentrating power of the cryoprecipitation
      process was not reduced for FVIII or fibrinogen in MB-treated units. MB
      cryoprecipitate from centre A still met the UK guideline specification for FVIII
      and fibrinogen content, whereas at centre B only 62.5% of the group O
      cryoprecipitates contained > 70 iu FVIII/unit. This may reflect the lower product
      volume and lower FVIII content of group O plasma used at centre B and suggests
      that maintenance of total coagulation factor recovery in MB-treated
      cryoprecipitate will require the higher product volume.

PMID- 10886223
TI  - Prognostic significance of cytogenetics in relapsed acute myeloid leukaemia.

PMID- 10886224
TI  - Length of first remission and karyotype: important prognostic factors for
      treatment of relapsed acute myeloid leukaemia.

PMID- 10886225
TI  - Hepatosplenic candidiasis in patients with acute leukaemia.

PMID- 10886226
TI  - Microparticles and reticulated platelets in Wiskott-Aldrich syndrome patients.

PMID- 10886227
TI  - Reply To matzdorff, kemkes-matthes and pralle

PMID- 10886228
TI  - Transfusion-related acute lung injury (Trali) in a patient with a single lung
      transplant.

PMID- 10886229
TI  - Absence of human herpesvirus 8 DNA sequences in leucapheresis products and bone
      marrow samples Of patients with advanced multiple myeloma.

PMID- 10886230
TI  - Clinical application of all-trans retinoic acid (tretinoin) for adult T-cell
      leukaemia.

PMID- 10886231
TI  - Immunodeficiency associated with DNA repair defects.

PMID- 10886232
TI  - Modulation of complement membrane attack by local C7 synthesis.

PMID- 10886233
TI  - Influence of fluticasone and salmeterol on airway effects of inhaled organic
      dust;an in vivo and ex vivo study.
AB  - Inhalation of dust from swine confinement buildings induces airway inflammation
      with an increase in both inflammatory cell numbers and secretion of
      proinflammatory cytokines in the lungs. It is not known whether anti-asthma
      drugs, which influence airway inflammation in asthma, also influence the airway
      reaction to inhaled organic dust. In the present study we examined the effects of
      a ss2-agonist (salmeterol) and an inhaled steroid (fluticasone) on the swine dust
      induced cell and cytokine content of the lower airways, and cytokine release in
      cultured alveolar macrophages. Healthy volunteers were pretreated with inhaled
      salmeterol (n = 8), fluticasone propionate (n = 8) or placebo (n = 8) for about 2
      weeks and exposed to dust in a pig house. Bronchoalveolar lavage was performed
      both before medication and after dust exposure. Cell differential counts and
      cytokine analyses in bronchoalveolar lavage fluid (BALF) were examined. Alveolar
      macrophages were cultured and cytokine release was studied, both in unstimulated
      cells and after lipopolysaccharide (LPS) stimulation. Unstimulated alveolar
      macrophages from swine dust-exposed individuals released less IL-6, IL-8 and
      tumour necrosis factor-alpha (TNF-alpha) after, than before, exposure (P < 0.01).
      Medication did not influence basal cytokine production. Fluticasone inhibited LPS
      induced IL-6 and IL-8 release (P < 0.05). There was no significant difference
      between the groups. There was a large and significant increase (P < 0.05) in
      alveolar macrophage, granulocyte, lymphocyte numbers, and IL-6 and TNF-alpha
      content in BALF in all three groups following dust exposure, with no significant
      difference between the groups. These findings suggest that drugs which are known
      to influence and control airway inflammation in asthma do not have major effects
      on airway inflammation induced by the inhalation of organic dust.

PMID- 10886234
TI  - Exogenous type-1 cytokines modulate mercury-induced hyper-IgE in the rat.
AB  - Suppression of IgE responses is a major goal for immunotherapy, especially in the
      field of allergy. The Th2 subset of helper T cells plays a vital role in class
      switching of B cells to IgE production by releasing IL-4. In susceptible rat
      strains, mercuric chloride (HgCl2) induces activation of Th2 cells, with enhanced
      expression of IL-4, polyclonal B cell activation and very high levels of
      circulating IgE. We have previously shown that spontaneous regulation of this
      response coincides with enhanced expression of Th1/type-1 cytokines, including
      interferon-gamma (IFN-gamma) and IL-12. We now report the effects of
      administration of exogenous type-1 cytokines on HgCl2-induced Th2 responses. At
      high doses, recombinant rat IFN-gamma markedly reduced serum IgE levels.
      Recombinant mouse IL-12 was less effective at suppressing the IgE response
      following HgCl2, although it caused marked up-regulation of IFN-gamma gene
      expression in the spleen. In Lewis rats, which are resistant to HgCl2-induced
      autoimmunity, a rise in serum IFN-gamma was observed after HgCl2, but
      administration of polyclonal anti-IFN-gamma antibodies did not render them
      susceptible to induction of a Th2 response by HgCl2. Our data show that
      individual type-1 cytokines are capable of suppressing the dramatic Th2 response
      induced by HgCl2 in the rat, even when they are not given until after starting
      HgCl2 administration. IFN-gamma is a pivotal cytokine in ameliorating the Th2
      response and measures aimed at selective up-regulation of this cytokine may be of
      therapeutic value in suppression of unwanted IgE responses.

PMID- 10886235
TI  - Characterization of mercuric mercury (Hg2+)-induced lymphoblasts from patients
      with mercury allergy and from healthy subjects.
AB  - Hg2+ induces lymphocyte proliferation when added to cell cultures from both
      healthy and mercury-allergic subjects. Consequently, when measuring DNA synthesis
      a possible Hg2+-specific response, resulting from proliferating memory cells,
      cannot be discriminated from a non-allergic response. The mechanism behind this
      non-allergic response is unknown but a superantigenic effect of Hg2+ has been
      suggested. In this study, five mercury-allergic patients, with oral lichen planus
      (OLP) lesions adjacent to dental amalgam and a positive patch test to Hg0, and
      five healthy subjects without amalgam were examined. The immunophenotype and the
      T cell receptor Vbeta (TCR Vbeta) repertoire of Hg2+-induced lymphoblasts as well
      as the expression of the lymphocyte activation markers CD23 and CD134 were
      analysed for possible differences between healthy and allergic subjects. The
      mechanism of Hg2+-induced proliferation was examined by comparing the TCR Vbeta
      expression of Hg- and staphylococcal enterotoxin B (SEB)-activated lymphoblasts,
      the latter used as a positive superantigen control. It was not possible to
      discriminate between mercury-allergic and healthy subjects using the
      immunophenotype or the TCR Vbeta profile of the Hg2+-induced lymphoblasts or the
      expression of CD23 and CD134. However, Hg2+-induced CD4+ lymphoblasts showed a
      skewing towards Vbeta2. This relative increase in Vbeta2 was only detected in the
      CD4+ but not in the CD8+ lymphoblast population. In conclusion, Hg2+ induced a
      proliferation-dependent skewing towards CD4+ but not CD8+ lymphocytes expressing
      Vbeta2. In this respect Hg2+ differs from the classical bacterial superantigen
      SEB, which also stimulates unique TCR Vbeta families among CD8+ cells.

PMID- 10886236
TI  - Human mast cell tryptase stimulates the release of an IL-8-dependent neutrophil
      chemotactic activity from human umbilical vein endothelial cells (HUVEC).
AB  - Tryptase, the major product of human mast cell activation, is a potent stimulus
      of vascular leakage and neutrophil accumulation in vivo in animal studies, but
      the mechanisms of action remain unclear. Using HUVEC cultures we have sought to
      investigate the potential of tryptase to alter monolayer permeability or induce
      the release of neutrophil chemotactic activity. Tryptase (1-100 mU/ml) failed to
      alter the permeability of endothelial cell monolayers as assessed by albumin flux
      over 1 h. However, supernatants from endothelial cells treated with tryptase (1
      50 mU/ml) for a 24-h period induced neutrophil migration across Transwell
      filters, with maximal migration observed at 10 mU/ml tryptase. Pretreatment of
      tryptase with the protease inhibitor leupeptin abolished the chemotactic
      activity, indicating a dependence on the catalytic site. Moreover, this effect
      was abolished by addition of an IL-8 neutralizing antibody, suggesting that IL-8
      release makes an important contribution to the chemotactic activity. The
      interaction of mast cell tryptase with endothelial cells could be important in
      stimulating the ingress of neutrophils following mast cell activation in
      inflammatory disease.

PMID- 10886237
TI  - IVIG-bound IgG and IgM cloned by phage display from a healthy individual reveal
      the same restricted germ-line gene origin as in autoimmune thrombocytopenia.
AB  - Intravenous immunoglobulin preparations (IVIG) have shown positive effects in the
      treatment of immune defects and autoimmune diseases. It is not clear how IVIG
      interacts with the components of the immune system. To investigate this, we
      cloned previously a large number of phage displayed IgG Fab fragments derived
      from three patients with autoimmune thrombocytopenia (AITP) that were
      specifically bound by IVIG molecules. Many of these Fabs reacted with platelets.
      Sequencing revealed that the most frequently used germ-line gene segments of all
      IVIG-bound Fabs were identical to those observed for many other autoantibodies.
      Particularly, the loci 3-30 or 3-30/3-30. 5, 3-23 and 3r, 3l, and 2a2 represented
      the most abundant genes used for the heavy (VH) and light chain V region (VL),
      respectively. This suggested a specific interaction of IVIG molecules with B
      cells that present B cell receptors derived from these germ-line genes. In the
      current study we determined the genetic origin of IVIG-reactive IgG and IgM
      cloned from a healthy person. A favoured selection of antibodies derived from the
      same germ-line origins as in AITP was observed. Because 3-30 and 3-23 are the
      most frequently rearranged VH germ-line gene segments among human B cells, our
      results suggest that this favoured anti-idiotypic interaction may have an
      important role for the development and control of the normal B cell repertoire.

PMID- 10886238
TI  - Polymorphisms in the IL-1 receptor antagonist gene VNTR are possible risk factors
      for juvenile idiopathic inflammatory myopathies.
AB  - Although HLA-DRB1 and -DQA1 alleles have been associated with adult and juvenile
      idiopathic inflammatory myopathies (JIIM), they only partially account for the
      genetic risk for these autoimmune disorders. Because IL-1alpha and IL-1beta, and
      the anti-inflammatory competitive inhibitor, IL-1 receptor antagonist (IL-1Ra),
      have been implicated in the pathogenesis of myositis, we assessed the role of
      variable number tandem repeat (VNTR) polymorphisms of the IL-1Ra gene (IL-1RN) in
      the aetiology of JIIM: IL-1RN VNTR polymorphisms were performed on 250 JIIM
      patients and 471 race-matched controls and were correlated with clinical
      characteristics. The IL-1RN A1 allele, associated with increased proinflammatory
      activity, was found to be a risk factor for Caucasians with JIIM (96.0% carriage
      rate versus 90.2% in race-matched controls, Pcorr = 0.037, odds ratio (OR) = 2.5,
      confidence interval (CI) = 1.1-5.8), but not for African-Americans, in whom the
      A3 allele was a possible risk factor (7.0% versus 1.1% in race-matched controls,
      Pcorr = 0.07, OR = 6.5, CI = 1.1-40.3). IL-1RN genotypes did not correlate with
      circulating levels of IL-1Ra, which were higher in patients than in controls. The
      polymorphic IL-1RN locus could be the first non-MHC genetic risk factor
      identified for JIIM, and different alleles may confer susceptibility for
      different ethnic groups.

PMID- 10886239
TI  - Clustering of distinct autoimmune diseases associated with functional
      abnormalities of T cell survival in children.
AB  - To ascertain whether alterations of lymphocyte switching off may be associated
      with clustering of autoimmune diseases in children, Fas- and C2-ceramide-induced
      cell death was evaluated on T cell lines derived from three patients affected by
      clustering of autoimmune disorders. Three patterns were found: patient 3 was
      resistant to Fas- and C2-ceramide, patient 1 was resistant to Fas, but sensitive
      to C2-ceramide, patient 2 was resistant to C2-ceramide, but sensitive to Fas. By
      contrast, Fas- and C2-ceramide-induced cell death was normal in five children
      with systemic juvenile rheumatoid arthritis, five children with insulin-dependent
      diabetes and 10 age-matched healthy controls. Surface expression of Fas was low
      in patient 1, but normal in patients 2 and 3. Together with normal Fas
      transcripts, patients 2 and 3 displayed a transcript 152 bp longer than the
      normal one retaining intron 5. Our data indicate that polyreactive autoimmune
      syndromes may be associated with heterogeneous alteration of the immune response
      switching-off system.

PMID- 10886240
TI  - Altered T cell development in human thymoma is related to impairment of MHC class
      II transactivator expression induced by interferon-gamma (IFN-gamma).
AB  - Thymoma is known to contain CD4+CD8+ T cells, indicating that neoplastic
      epithelial cells of thymoma have a function as thymic cortical epithelium.
      However, it has been shown that there is an impairment of CD4+ T cell development
      in thymoma and that IFN-gamma-induced HLA-DR expression on cultured thymic
      epithelial cells (TEC) derived from thymoma is decreased when compared with the
      normal thymus. MHC class II transactivator (CIITA) is known to play a critical
      role in IFN-gamma-induced MHC II expression. In this study, we attempted to
      elucidate whether CIITA is responsible for the impaired up-regulation of MHC II
      molecules in response to IFN-gamma in thymoma TEC. A quantitative reverse
      transriptase-polymerase chain reaction examination revealed that the induced
      level of CIITA was significantly lower in thymoma TEC than in normal TEC. The
      induced levels of invariant chain (Ii) and HLA-DR in thymoma TEC were correlated
      with CIITA expression. The proportion of CD3+ cells in the CD4+CD8- subset in
      thymoma was also correlated with CIITA expression. A gel mobility shift assay
      however, revealed translocation of STAT1 to the nucleus in thymoma as well as
      normal TEC. Intercellular adhesion molecule-1 was up-regulated in the thymoma TEC
      to a level similar to normal TEC in response to IFN-gamma. These results indicate
      that impaired up-regulation of HLA-DR in response to IFN-gamma results from
      insufficient induction of CIITA, but not from the signal from IFN-gamma receptor
      to the nucleus. The abnormal regulation of HLA-DR expression caused by impaired
      induction of CIITA may affect CD4+ T cell development in thymoma.

PMID- 10886241
TI  - The endothelium is an extrahepatic site of synthesis of the seventh component of
      the complement system.
AB  - The level of the terminal complement components secreted by human umbilical vein
      endothelial cells (HUVEC) was measured by a sensitive ELISA which allows the
      detection of 30-50 pg/ml of these components. C7 was the only terminal component
      detected in measurable amounts in the cell supernatant. The mean value was 11
      ng/106 cells at 96 h and was slightly higher than that of C3 (9 ng/106 cells).
      HUVEC and serum C7 analysed by SDS-PAGE and immunoblot exhibited the same
      electrophoretic mobility. A proportion of C7 secreted by HUVEC was incorporated
      into the terminal complement complex (TCC) assembled spontaneously in the
      supernatant of cells cultured in C7-deficient human serum, and was not detected
      by the standard ELISA for C7 measurement. By adding the amount of C7 present in
      the TCC to that of free C7, the total amount of the component released by HUVEC
      was calculated to be approximately 35 ng/106 cells. Further TCC was produced
      following complement activation of the cell supernatant through the alternative
      pathway. Synthesis of C7 by HUVEC was confirmed by inhibition experiments in the
      presence of cycloheximide and by reverse transcriptase-polymerase chain reaction
      (RT-PCR) analysis of C7 mRNA expression. Addition of IL-1alpha and tumour
      necrosis factor-alpha to the cell culture stimulated the secretion of C3, but had
      no effect on the synthesis of C7. By contrast, interferon-gamma had only a
      marginal effect on the production of C3, but markedly down-regulated the
      synthesis of C7 as assessed both by ELISA and RT-PCR.

PMID- 10886242
TI  - Effects of secretory leucocyte protease inhibitor on the production of the anti
      inflammatory cytokines, IL-10 and transforming growth factor-beta (TGF-beta), by
      lipopolysaccharide-stimulated macrophages.
AB  - We studied the effects of secretory leucocyte protease inhibitor (SLPI) on the
      production of the anti-inflammatory cytokines, IL-10 and TGF-beta, by
      lipopolysaccharide (LPS)-stimulated macrophages, using half-sized SLPI (1/2 SLPI)
      containing the C-terminal domain (Arg58-Ala107). ELISA testing of macrophage
      culture fluids showed a temporary production of IL-10 by the macrophages in the
      early phase (24 h) after LPS stimulation at low (1 ng/ml) or high (10 microg/ml)
      concentrations. On the other hand, TGF-beta production was initiated after day 3
      and progressively increased. 1/2 SLPI significantly increased IL-10 and TGF-beta
      production by macrophages in response to a low dose as well as a high dose of
      LPS. Reverse transcription-polymerase chain reaction analysis showed that 1/2
      SLPI caused a significant increase in the expression of both IL-10 and TGF-beta
      mRNAs by LPS-stimulated macrophages. Thus, although the profile of macrophage TGF
      beta production by LPS-stimulated macrophages is markedly different from that of
      their IL-10 production, SLPI causes an up-regulation of the production of these
      anti-inflammatory cytokines by LPS-stimulated macrophages.

PMID- 10886243
TI  - Differences in regulatory pathways identify subgroups of T cell-derived Th2
      cytokines.
AB  - We analysed regulatory mechanisms involved in the production of Th2 cytokines by
      freshly isolated human T cells. We used an in vitro culture system in which the
      primary signal was provided by a cross-linking anti-CD3 MoAb presented on the Fc
      receptors of P815 cells. Both CD80 and CD86, expressed on transfected P815 cells,
      were able to provide efficient costimulation for the production of IL-4, IL-5 and
      IL-13. IL-2 was also highly important for induction of all three Th2 cytokines.
      However, differences between IL-4 on the one hand and IL-5 and IL-13 on the other
      hand were observed when sensitivity to cyclosporin A (CsA) was studied. CsA (an
      inhibitor of calcineurin phosphatase activity) strongly inhibited IL-4
      production, but it did either not affect or even increased IL-5 and IL-13
      production. In accordance with this, CD80 and phorbol myristate acetate (PMA)
      (without anti-CD3 or calcium ionophore) were sufficient to induce production of
      IL-5 and IL-13, but not of IL-4. The subgrouping of Th2 cytokines was further
      confirmed at another level on the basis of differences in cell sources: IL-4 was
      predominantly produced by CD4+ T cells, while IL-5 and IL-13 were produced by
      both CD4+ and CD8+ T cells. Thus, differences in cell sources and in the
      requirement of the calcium/calcineurin-signalling pathway allowed us to identify
      two subgroups (IL-4 and IL-5/IL-13) among human Th2-type T cell cytokines.

PMID- 10886244
TI  - Accumulation of CD4+CD7- T cells in inflammatory skin lesions: evidence for
      preferential adhesion to vascular endothelial cells.
AB  - The CD7- subset of CD4+ memory T cells reflects a stable differentiation state of
      post-thymic helper T cells and represents a small subpopulation in circulating
      blood. We here demonstrate that CD7- T cells preferentially accumulate in skin
      lesions under chronic inflammatory conditions irrespective of the particular
      disease. As adhesion to vascular endothelial cells (EC) is required for migration
      of circulating lymphocytes into tissues, we analysed the adherence of purified
      subsets of CD4+ memory T cells to endothelial cells in vitro. Compared with
      CD4+CD7+ T cells, cells of the CD4+CD7- subset preferentially adhere to EC, which
      is moreover increased after prestimulation of EC with tumour necrosis factor
      alpha (TNF-alpha). Stimulated EC increase expression of intercellular adhesion
      molecule-1 (CD54) and E-selectin (CD62E), the ligand of which, cutaneous
      lymphocyte-related antigen (CLA), is highly expressed in CD4+CD7- T cells but not
      in CD4+CD7+ T cells. LFA-1 is expressed in a bimodal distribution on CD4+CD7- T
      cells in contrast to CD4+CD7+ cells, whereas VLA-1, VLA-3, and VLA-5 are nearly
      similarly expressed in both T cell subsets. Our results imply that the preferred
      adherence of CD4+CD7- memory T cells to vascular EC, which is increased after
      long-term EC stimulation with TNF-alpha, is likely to facilitate their
      accumulation in various inflammatory skin lesions.

PMID- 10886245
TI  - Evidence for recognition of novel islet T cell antigens by granule-specific T
      cell lines from new onset type 1 diabetic patients.
AB  - Type 1 diabetes is a T cell-mediated autoimmune disease where a number of islet
      beta-cell target autoantigens have been characterized on the basis of reactivity
      with autoantibodies. Nevertheless, there remains uncertainty of the nature of
      another group of autoantigens associated with the secretory granule fraction of
      islet beta-cells that appear to be targeted predominantly by autoreactive T
      cells. We have previously characterized CD4+, HLA-DR-restricted T cell lines from
      new onset type 1 diabetic patients that are specific for the secretory granule
      fraction of rat tumour insulinoma, RIN. The T cell line from the first patient,
      HS, proliferates in response to crude microsomal membranes prepared from a
      recently established, pure human islet beta-cell line NES2Y. In addition, the HS
      line also responds to secretory granule fractions prepared from a murine tumour
      insulinoma grown in RIP-Tag mice, showing the recognition of species-conserved
      antigen(s) in beta-cells. Using partially matched antigen-presenting cells, the
      HS T cells and another line derived from a second patient, MR, were shown to be
      restricted by disease-associated DRB1*0101 and DRB1*0404 alleles, respectively.
      Neither the HS or MR T cell lines proliferate in response to a large panel of
      candidate islet cell antigens, including insulin, proinsulin, glutamic acid
      decarboxylase, the protein tyrosine phosphatase IA-2/phogrin, imogen-38, ICA69 or
      hsp60. Our data provide compelling evidence of the presence of a group of
      antigens associated with the secretory granule fraction of islet beta-cells
      recognized by the T cell lines, whose definition may contribute to our knowledge
      of disease induction as well as to diagnosis.

PMID- 10886246
TI  - Neutrophil lactoferrin release induced by IgA immune complexes differed from that
      induced by cross-linking of fcalpha receptors (FcalphaR) with a monoclonal
      antibody, MIP8a.
AB  - The human IgA Fc receptor (FcalphaR, CD89) plays an important role in host
      defence against invading pathogens. To study the properties of the receptor, 12
      MoAbs, namely, MIP7c, MIP8a, MIP9a, MIP10c, MIP11c, MIP14b, MIP15b, MIP38c,
      MIP59c, MIP65c, MIP68b and MIP71a, were generated. The inhibitory effects of the
      antibodies on FcalphaR functions were tested. Three of the antibodies, MIP7c,
      MIP8a and MIP59c, were able to block up to 90% of soluble FcalphaR binding to IgA
      coated beads and 70-80% of neutrophil phagocytosis of IgA immune complexes (IC).
      MIP8a could also inhibit IgA IC-induced neutrophil lactoferrin release, while
      cross-linking of FcalphaR with MIP8a and anti-mouse IgG could elicit neutrophil
      lactoferrin release. However, IgA IC-induced lactoferrin release required both
      extracellular calcium and magnesium, whereas MIP8a-induced release did not
      require extracellular magnesium and only partially required extracellular
      calcium. In addition, the time course of IgA IC-induced lactoferrin release was
      slow. Lactoferrin was not detectable if the incubation time was less than 0.5 h.
      In contrast, MIP8a-induced lactoferrin release was fast. Lactoferrin could be
      detected within 5 min of incubation. Therefore, neutrophil lactoferrin release
      induced by IgA IC differed from that induced by cross-linking of FcalphaR with
      MIP8a.

PMID- 10886247
TI  - Differential regulation of nitric oxide synthase isoforms in experimental acute
      chagasic cardiomyopathy.
AB  - We have previously demonstrated induction and high level expression of IL-1beta,
      IL-6 and tumour necrosis factor-alpha in the myocardium during the acute stage of
      experimental Trypanosoma cruzi infection (Chagas' disease). The myocardial
      depressive effects of these cytokines are mediated in part by the induction of
      nitric oxide synthase (NOS), production of nitric oxide (NO) and formation of
      peroxynitrite. In this study we investigated the expression, activity and
      localization of NOS isoforms, and the levels of NO, malondialdehyde (a measure of
      oxidative stress), and peroxynitrite in rats at 1.5, 5, 10 and 15 days after
      infection with T. cruzi trypomastigotes. The myocardial inflammatory infiltrate
      and number of amastigote nests increased over the course of infection. A
      significant increase in tissue nitrate + nitrite levels, NOS2 mRNA, and NOS2
      enzyme activity was observed at all time points in the infected compared with
      uninfected animals. The enzyme activity of constitutive NOS, tissue
      malondialdehyde levels, and NOS3 mRNA levels was only transiently increased after
      infection. The protein levels of the NOS isoforms paralleled their mRNA
      expression. While no positive nitrotyrosine immunoreactivity was detected in
      control myocardium, its levels increased in infected animals over time. Thus, by
      1.5 days post-infection, when no parasite or immune cell infiltration could be
      detected, the myocardium expressed high levels of NOS and NO metabolites.
      Nevertheless, the early production of NO in the myocardium was not sufficient to
      clear the parasites.

PMID- 10886248
TI  - Analysis of T cell repertoire in the liver of patients with chronic hepatitis C.
AB  - Many T cells infiltrate into the liver of patients with chronic hepatitis C (CH
      C). They are believed to play a crucial role in the immunopathogenesis of hepatic
      inflammation, but their clonality and specificity are unknown. The aim of this
      study was to clarify the characteristics of these T cells. We analysed the
      complementarity-determining region (CDR)3 size lengths of T cell receptor (TCR)
      beta-chains by size spectratyping, and determined the sequences of Vbeta CDR3
      after subcloning Vbeta-specific polymerase chain reaction products. Spectratyping
      showed clonal expansions in all liver specimens, most of which showed more than
      two T cell clones. Moreover, many non-clonal T cells also accumulated in the
      liver. Clonality of the T cells suspected by spectratyping was confirmed by CDR3
      sequencing. Although the sequences revealed no whole CDR3-shared clones among
      different patients, some common motif sequences were observed. Our data suggest
      that T cells are stimulated by several hepatitis C virus (HCV) epitopes, then
      accumulate in the liver of CH-C patients. Shared motifs of expanded T cell clones
      suggest that they might recognize the same regions of HCV peptides, but have
      differences due to HCV peptide mutational changes. These clones might also
      interact with non-clonal T cells and play a crucial role in the
      immunopathogenesis of CH-C.

PMID- 10886249
TI  - T cell receptor repertoire and function in patients with DiGeorge syndrome and
      velocardiofacial syndrome.
AB  - DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) are associated with
      chromosome 22q11.2 deletion. Limited information is available on the T cell
      receptor (TCR) Vbeta repertoire. We therefore investigated TCR Vbeta families in
      lymphocytes isolated from blood and thymic samples of seven patients with DGS and
      seven patients with VCFS, all with 22q11.2 deletion. We also studied activities
      related to TCR signalling including in vitro proliferation, anti-CD3-induced
      protein tyrosine phosphorylation, and susceptibility to apoptosis. Reduced CD3+ T
      cells were observed in most patients. Spontaneous improvement of T cell numbers
      was detected in patients, 3 years after the first study. Analysis of CD4+ and
      CD8+ TCR Vbeta repertoire in peripheral and thymic cells showed a normal
      distribution of populations even if occasional deletions were observed.
      Lymphoproliferative responses to mitogens were comparable to controls as well as
      anti-CD3-induced protein tyrosine phosphorylation. Increased anti-CD3-mediated
      apoptosis was observed in thymic cells. Our data support the idea that in
      patients surviving the correction of cardiac anomalies, the immune defect appears
      milder than originally thought, suggesting development of a normal repertoire of
      mature T cells.

PMID- 10886250
TI  - A novel point mutation in CD18 causing the expression of dysfunctional CD11/CD18
      leucocyte integrins in a patient with leucocyte adhesion deficiency (LAD).
AB  - Leucocyte adhesion deficiency type 1 (LAD-1) is characterized by the incapacity
      of leucocytes to carry out their adhesion functions via their CD11/CD18 antigens,
      which are also referred to as the leucocyte integrins. The patients generally
      suffer from poor wound healing and recurrent bacterial and fungal infections. In
      severe cases, the infections are often systemic and life-threatening. A LAD
      patient (AW) of moderate phenotype has been identified but, unlike most other
      cases, the level of CD11/CD18 antigens on her leucocytes are uncharacteristically
      high for a LAD patient. Molecular analysis revealed that she is a compound
      heterozygote for CD18 mutations. She has inherited a D231H mutation from her
      father and a G284S mutation from her mother. By transfection studies, it was
      established that the G284S mutation does not support CD11/CD18 antigen expression
      on the cell surface. In contrast, the D231H mutation does not affect CD18 forming
      integrin heterodimers with the CD11 antigens on the cell surface. However, the
      expressed integrins with the D231H mutation are not adhesive to ligands.

PMID- 10886251
TI  - Intravenous immunoglobulin (IVIG) attenuates antibody binding in acute
      haemorrhagic immunopneumonitis in a rat model of complement-dependent lung
      injury.
AB  - Administration of rabbit anti-rat lung serum (PNTS) to rats produces a fulminant
      haemorrhagic pneumonitis sensitive to the availability of complement. The present
      experiments were undertaken to assess whether a high dose of IVIG can affect the
      development of this kind of cytotoxic reaction. The experimental design included
      groups of Wistar rats pretreated intravenously with physiologic saline, IVIG or a
      preparation of human F(ab')2 fragments. One hour later the animals were
      challenged with either saline or PNTS. At 30 min after challenge, blood was
      collected and the lungs were removed. Pulmonary damage was evaluated by light
      microscopy; C3 deposits and the binding of immunoglobulins to the alveolar septa
      were assayed by immunofluorescence. The serum complement activity of the
      classical and alternative pathways was estimated by a kinetic technique.
      Pretreatment with IVIG decreased binding of rabbit anti-lung antibodies to
      alveolar septa and prevented the deposition of C3. These results indicate that
      pretreatment with IVIG inhibits the binding of the pathogenic antibody to lung
      tissue. Human IgG binding was not detected in any animal. The protection against
      lung injury afforded by pretreatment with IVIG, in contrast to the pneumotoxic
      effect of PNTS observed in control animals, was evident despite the
      administration of F(ab')2 to the rats. Since pretreatment with F(ab')2 failed to
      prevent the acute lung lesion, our results indicate that the attenuation afforded
      by IVIG in this model of complement-dependent tissue injury seems to be related
      to the integrity of the IgG molecule.

PMID- 10886252
TI  - Possible role of L-selectin in T lymphocyte alveolitis in patients with active
      pulmonary sarcoidosis.
AB  - A number of adhesion molecules participate in the recruitment of inflammatory
      cells to the site of inflammation, and selectins together with their ligands are
      important in the early transient adhesion phase. In this study, we evaluated the
      role of L-selectin in T lymphocyte alveolitis in patients with active pulmonary
      sarcoidosis. We measured serum and bronchoalveolar lavage fluid (BALF)
      concentrations of soluble (s)L-selectin using an ELISA. Serum and BALF
      concentrations of sL-selectin were significantly elevated in patients with
      sarcoidosis compared with control healthy subjects and idiopathic pulmonary
      fibrosis (IPF) patients (P < 0.05 and P < 0. 01, respectively). The lymphocyte
      surface marker was also examined in peripheral blood and BALF by flow cytometric
      analysis. The percentage of CD3+CD62L+ cells (L-selectin-bearing T lymphocytes)
      was significantly lower in peripheral blood of sarcoidosis than in that of
      healthy subjects (P < 0.01). In contrast, the percentage of CD3+CD62L- cells (L
      selectin-negative T lymphocytes) in BALF of patients with sarcoidosis was
      significantly higher than in healthy subjects (P < 0.05) and IPF patients (P <
      0.01). Furthermore, there was a significant correlation between serum
      concentrations of sL-selectin and the number of L-selectin-negative T lymphocytes
      in BALF (r = 0.535, P < 0.01). Our results suggest that L-selectin may be
      involved in T lymphocyte alveolitis in patients with active pulmonary
      sarcoidosis.

PMID- 10886253
TI  - Peptide T does not ameliorate experimental autoimmune encephalomyelitis (EAE) in
      Lewis rats.
AB  - Peptide T has been shown to inhibit T cell activation and cytokine production and
      function. Moreover, it has been reported to be a safe treatment in humans. We
      have studied the ability of peptide T to prevent or ameliorate EAE in Lewis rats.
      Peptide T was administered subcutaneously at different doses and phases of the
      disease according to several treatment protocols, but we could not observe a
      consistent effect of peptide T ameliorating the disease. Lymph node cell
      proliferation and IL-4 and interferon-gamma production were also studied. We
      conclude that peptide T neither prevents nor ameliorates EAE in Lewis rats.

PMID- 10886255
TI  - Target antigens for anti-neutrophil cytoplasmic autoantibodies (ANCA) are on the
      surface of primed and apoptotic but not unstimulated neutrophils.
AB  - The reaction of ANCA with ANCA antigens on the surface of neutrophils may play a
      critical role in the pathogenesis of ANCA vasculitis. Therefore, an understanding
      of the circumstances that result in surface expression of these antigens is
      important for an understanding of pathogenic mechanisms. In this study we
      investigated the surface expression of ANCA antigens on quiescent, primed, and
      apoptotic neutrophils. ANCA antigens and other granule constituents were not
      detected on the surface of neutrophils in freshly heparinized blood. ANCA
      antigens were on the surface of neutrophils primed by in vitro incubation for 4 h
      and 8 h. These cells did not show evidence of apoptosis. After 24 h incubation,
      about 30% of the neutrophils were apoptotic, and ANCA antigens and other granule
      constituents were present on the surface of both apoptotic and non-apoptotic
      cells. Our data indicate that there are no ANCA antigens on the surface of
      quiescent neutrophils, but that they are on the surface of primed neutrophils
      before the cells become apoptotic, and remain on the surface of cells after they
      become apoptotic. Based on these observations, we hypothesize that ANCA can react
      in vivo with primed but not quiescent neutrophils. Previously published
      observations indicate that the interaction of ANCA with primed neutrophils
      results in neutrophil activation, which may be involved in the pathogenesis of
      ANCA vasculitis.

PMID- 10886254
TI  - T cell lines specific for a synthetic Heymann nephritis peptide derived from the
      receptor-associated protein.
AB  - Pathogenic antigens involved in the induction of Heymann nephritis (HN), an
      experimental rat model of human membranous nephritis, have been identified in
      megalin (gp330) and the receptor-associated protein (RAP) [1,2]. A pathogenic
      epitope has been identified in RAP (amino acid 1-86) that plays a significant
      role in the formation of immune deposits in glomeruli in HN. A synthetic peptide
      (P31-53) derived from RAP1-86 contains a pathogenic epitope recognized by
      antibodies eluted from glomerular immune deposits and includes two putative RT
      1B1 MHC class II-binding motifs. We have investigated whether RAP P31-53 can be
      recognized by T cells. Five peptide-specific T cell lines were generated from
      regional lymph node (LN) T cells from Lewis rats immunized with P31-53. The T
      cell lines were characterized by using a T cell proliferation assay for their
      specificity, FACS and MHC restriction assay for the phenotype, reverse
      transcription-polymerase chain reaction for TCR Vbeta repertoire and cytokine
      expression, and cloning and sequencing for the analysis of the CDR3 sequence of
      TCR. The helper function of the T cell line was confirmed by autoantibody
      production in vitro. In this study, we clearly identify that the synthetic
      pathogenic peptide P31-53 contains a T cell epitope recognized by CD4+ Th2 cells
      in Lewis rats. This recognition was restricted by MHC class II RT1.B1. These CD4+
      Th2 cells were able to promote B cells to produce specific antibodies and used a
      restricted set of TCR Vbeta genes with preferential usage of Vbeta18. A charged
      amino acid motif at the CDR3 region of predominant TCR Vbeta subfamilies may
      contribute to the specific ability of these cells to recognize the immunogenic T
      cell epitope within RAP peptide P31-53.

PMID- 10886256
TI  - Scandinavian test of artificial neural network for classification of myocardial
      perfusion images.
AB  - Artificial neural networks are systems of elementary computing units capable of
      learning from examples. They have been applied to automated interpretation of
      myocardial perfusion images and have been shown to perform even better than
      experienced physicians. It has been shown that physicians interpreting myocardial
      perfusion images benefit from the advice of such networks. These networks have
      been developed and validated in the same hospital. However, widespread use of
      neural networks will only take place if the networks can maintain a high accuracy
      in other hospitals, i.e. hospitals using different gamma cameras, different
      acquisition techniques, different study protocols, etc. The purpose of this study
      was to develop a neural network in one hospital and test it in another. An
      artificial neural network was trained to detect coronary artery disease using
      myocardial perfusion scintigrams from 135 patients at a Swedish hospital.
      Thereafter, this network was tested using scintigrams from 68 patients at a
      Danish hospital and compared to six criteria based on expert physician analysis
      and quantitative analysis by the CEqual program. The sensitivity of the network
      was significantly higher than that of one of the physician criteria (0. 92 versus
      0.71) and two of the CEqual-based criteria (0.94 versus 0. 63 and 0.96 versus
      0.65) compared at equal specificities. It was concluded that an artificial neural
      network can maintain high accuracy in a hospital other than the one where it was
      developed.

PMID- 10886257
TI  - Simplified scintigraphic methods for measuring gastrointestinal transit times.
AB  - To investigate whether simple transit measurements based on scintigraphy
      performed only 0, 2, 4 and 24 h after intake of a radiolabelled meal can be used
      to predict the mean transit time values for the stomach, the small intestine, and
      the colon, a study was conducted in 16 healthy volunteers. After ingestion of a
      meal containing 111indium-labelled water and 99mtechnetium-labelled omelette,
      imaging was performed at intervals of 30 min until all radioactivity was located
      in the colon and henceforth at intervals of 24 h until all radioactivity had
      cleared from the colon. Gastric, small intestinal and colonic mean transit times
      were calculated for both markers and compared with fractional gastric emptying at
      2 h, fractional colonic filling at 4 h, and geometric centre of colonic content
      at 24 h, respectively. Highly significant correlations were found between gastric
      mean transit time and fractional gastric emptying at 2 h (111In: r=0.95,
      P<0.00001; 99mTc: r=0.96, P<0.00001), between small intestinal mean transit time
      and fractional colonic filling at 4 h (111In: r=-0.97, P<0.00001; 99mTc: r=-0.89,
      P<0. 00001), and between colonic mean transit time and geometric centre of
      colonic content at 24 h (111In: r=- 0.88, P<0.00001). We therefore conclude that
      reliable regional gastrointestinal transit times can be estimated from
      scintigraphic images taken 0, 2, 4 and 24 h after intake of radiolabelled
      markers.

PMID- 10886258
TI  - Body composition in italian and Danish women.
AB  - The objective of this cross-sectional study was to compare the body composition
      and fat distribution measured by dual energy X-ray absorptiometry (DPX, Lunar) in
      different age decades of age-matched Danish and Italian women. The subjects
      comprised 133 healthy Italian women (age 20-60 years) age-matched to a
      representative sub-sample of healthy Danish women (n=375). Total and abdominal
      body fat tissue mass were measured by dual-energy X-ray absorptiometry. Italian
      women were shorter and fatter compared with age-matched Danish women, but in
      middle-age, had a less abdominal fat distribution. There was no difference in
      total body bone mineral density.

PMID- 10886260
TI  - Effects of silicone breast prostheses on the assessment of body composition by
      dual-energy X-ray absorptiometry.
AB  - We examined the influence of silicone breast prostheses on body composition as
      assessed by dual-energy X-ray absorptiometry (DXA). Eighteen women were measured
      with and without a pair of silicone breast prostheses placed on the upper part of
      the trunk simulating endogenous implants. Bone area, bone mineral content (BMC),
      areal bone mineral density (BMD), lean tissue mass (LTM) and fat tissue mass
      (FTM) of the total body and of the subregions of the body, i.e. the head, trunk,
      arms and legs, were measured by a Norland XR-36 DXA scanner. After application of
      the silicone prostheses, bone area, BMC and BMD of the total body significantly
      increased by an average of 3.7, 6.6 and 3.4% (P<0.0001), respectively. Total body
      LTM and FTM were not affected. In the trunk region, changes were more pronounced.
      Trunk BMC, for example, was overestimated by 17.9% (P<0. 0001). The prostheses
      also influenced measurements of truncal soft tissue composition, with a small but
      statistically significant overestimation of both LTM (1.1%) and FTM (2.1%)
      (P<0.05). No changes in bone mass and soft tissue composition were seen in the
      head, arms and legs. Activation of a high-density detection software utility
      provided by the manufacturer had no influence on any of the measurements. We
      conclude that silicone breast prostheses affect the assessment of body
      composition by DXA.

PMID- 10886259
TI  - Influence of body size and age on maximal systolic velocity of mitral annulus
      motion.
AB  - The maximal systolic velocity of the mitral annulus motion (or maximal systolic
      long-axis contraction velocity of the ventricle, MLACV) has been suggested as a
      means to assess left ventricular function. However, reference values for a wide
      range of age and body size are lacking. The maximal systolic velocity was studied
      with M-mode echocardiography using the apical four- and two-chamber views. Data
      are reported as the average of the measurements of four sites of the mitral
      annulus. Fifty-seven healthy subjects aged 6 months to 72 years were studied. In
      children and adolescents up to age 18, MLACV had a significant positive
      correlation with age, height, body surface area, weight and mitral annulus motion
      amplitude and a significant negative correlation with heart rate. In adults,
      there was a significant positive correlation between MLACV and height, mitral
      annulus motion amplitude and body surface area and a significant negative
      correlation with age and heart rate. Multiple stepwise analysis showed that the
      maximal systolic velocity is highly dependent on height and age in children and
      adolescents up to age 18, and on height in adults. The maximal long-axis
      contraction velocity (MLACV) can be described by the following equations: MLACV
      (mm s-1) = 24.0 + 0.34 x height (cm) (Standard Error of the Estimate (SEE)=10.5)
      in children and adolescents, and MLACV (mm s-1) = -50.5 + 0.75 x height (cm)
      (SEE=9.8) in adults over 18. There were significant differences between the four
      sites, with the highest velocity at the lateral site and the lowest velocity at
      the septal site. No significant difference was found between inspiratory and
      expiratory beats.

PMID- 10886261
TI  - Comparison of bioimpedance and radioisotope methods in the estimation of
      extracellular water volume before and after coronary artery bypass grafting
      operation.
AB  - To estimate extracellular water volume (ECW) changes in connection with coronary
      artery bypass grafting operation, simultaneous ECW estimations by 51Cr-EDTA
      dilution and whole-body bioimpedance techniques were performed in 15 patients.
      The assessments of ECW were compared with patients' weighing results. Whole-body
      bioimpedance-derived ECW correlated significantly with 51Cr-EDTA dilution-based
      ECW in the pre-operative period (r=0.74; P<0.005); the bias was 0.2 +/- 1.1 l (+/
      SD). In the post-operative period, the agreement between these methods was poor,
      the bias being 0.5 +/- 2.5 l, and no significant correlation between the methods
      was found (r=0.38; P>0.05). Whole-body bioimpedance-derived ECW changes
      correlated significantly with weight changes of the patient induced by the
      operation (r=0.52; P<0.05). 51Cr-EDTA dilution-based ECW changes correlated
      neither with weight changes (r=0.33; P>0.05) nor with bioimpedance-derived ECW
      changes (r=0.03; P>0.05). Alterations in radioisotope tracer distribution and
      loss of it due to blood leakage in the post-operative period were presumed to
      explain the discrepancy between dilution technique and weighing results. The
      results suggest that bioimpedance is a useful non-invasive method for assessment
      of extracellular volume changes induced by coronary artery bypass grafting
      operations. 51Cr-EDTA dilution-based ECW determination is not suitable in related
      conditions.

PMID- 10886262
TI  - Cerebral haemodynamics during the Mueller manoeuvre in humans.
AB  - Voluntary negative intra-thoracic pressure (Mueller manoeuvre) is known to reduce
      arterial blood pressure (ABP). To investigate changes in cerebral blood flow
      velocity (CBFV) during 15 s Mueller manoeuvres at -30 mmHg intra-thoracic
      pressure, 27 young (aged 21-31 years, group A) and 11 older (52-64 years, group
      B) healthy adults were studied using transcranial Doppler and non-invasive ABP
      measurement (Finapres). After closely following the initial ABP drop, CBFV showed
      an overshoot during temporary recovery of ABP. Then ABP and CBFV decreased
      significantly to below baseline. While ABP declined further until the end of the
      manoeuvre, CBFV increased in group A 4.7 s (2.4-8.5) (median and range) and in
      group B 5.7 s (4. 1-7.2) after the onset of the CBFV decrease. Critical closing
      pressure (CCP), calculated for each cardiac cycle from the dynamic pressure-flow
      relationship (DPFR), indicated a reduction of intra-cranial pressure during the
      first half of the strain. DPFR-related estimation of cerebrovascular resistance
      provided a more physiological response than the conventional cerebrovascular
      resistance quotient ABP/CBFV, and decreased about 1.5 s before the observed CBFV
      increase. A modification of the previously described dynamic auto-regulation
      index ROR correlated significantly with CO2 reactivity values (r=0.61, P=0.001).
      In conclusion, changes in CBFV during Mueller manoeuvres are likely to reflect
      dynamic cerebral auto-regulation and may provide an estimate of dynamic cerebral
      auto-regulation capacity. In older adults, the maximal dynamic auto-regulatory
      response seems to be unchanged, but the onset of reaction is slightly delayed.

PMID- 10886263
TI  - Lipoproteins and free plasma catecholamines in spinal cord injured men with
      different injury levels.
AB  - Persons with spinal cord injury (SCI) are especially prone to atherogenesis. This
      is partly explained by an unfavourable lipoprotein profile in these individuals.
      The impairment of the sympathetic nervous system, and the fact that SCI subjects
      are subject to extreme physical inactivity, may have an influence on their lipid
      profile and lipoprotein(a) concentration. We made a detailed investigation of the
      lipid profile as well as serum levels of adrenaline and noradrenaline in 80 men
      with SCI ranging from tetraplegia to low paraplegia and in 16 control subjects.
      The lipid profile of tetraplegics was characterized by elevated very low-density
      lipoprotein cholesterol and triglyceride levels and reduced high-density
      lipoprotein levels. In contrast, paraplegics had significantly higher low-density
      lipoprotein and total cholesterol levels. Tetraplegics had lower and the low
      lesion paraplegics had higher adrenaline and noradrenaline levels than the high
      lesion paraplegics and the control subjects. High-lesion SCI subjects also showed
      an extreme reduction in VO2max. The lipoprotein profile was dependent on the
      injury level and serum catecholamine concentrations. The lower the noradrenaline
      values, the lower the high-density lipoprotein cholesterol. The low-density
      lipoprotein also correlated to catecholamines and particularly adrenaline values.
      Despite the correlation between lipoprotein(a) and adrenaline, no significant
      differences in lipoprotein(a) were found within SCI individuals as well as
      between SCI individuals and control subjects, indicating the predominantly
      genetic determination of lipoprotein(a) and thus the cardiovascular risk.
      Different serum catecholamine levels due to impairment of sympathetic nervous
      system and VO2max levels were observed in SCI subjects. This was associated with
      a higher lipid risk profile for cardiovascular diseases; however, the risk
      profile is dependent on the lesion level.

PMID- 10886264
TI  - Brozek two-compartment model under-estimates body fat in black female athletes.
AB  - The purpose of this study was to compare percentage body fat (%BF) values of
      black female athletes calculated using the Heymsfield four-compartment (4C),
      Brozek two-compartment (2C) and Schutte models. Eleven collegiate athletes
      underwent total body water (TBW) assessment, hydrostatic weighing (HW) and dual
      energy X-ray absorptiometry (DXA). Repeated-measures ANOVA determined that the 4C
      model yielded %BF values (16.2 +/- 1.5%) that were higher than the Brozek model
      (13.6 +/- 1.7%) but similar to the Schutte model (16.7 +/- 1.6%). The fat-free
      mass density of the athletes (1.109 +/- 0. 002 kg l-1) was significantly higher
      than the value 1.1 kg l-1 assumed by the 2C model. We conclude that in lean black
      female athletes, the Brozek 2C model under-estimates %BF, and that, if only HW is
      available, the Schutte model should be used to estimate %BF.

PMID- 10886265
TI  - Does the specialty of the physician affect fatality rates in liposuction? A
      comparison of specialty specific data.

PMID- 10886266
TI  - The history of dermatology in American phlebology.

PMID- 10886267
TI  - Fusiform incisional biopsy for pigmented skin lesions.
AB  - Current recommendations for biopsy of a pigmented skin lesion suspected of being
      melanoma include complete excision when possible. Because benign pigmented
      lesions do not warrant excisional biopsy, especially when they are large and/or
      on cosmetically sensitive sites, incisional biopsy is desirable. For such lesions
      we recommend a fusiform incisional biopsy. This tissue sampling technique not
      only yields an excellent cosmetic outcome, but also provides the pathologist with
      an optimal biopsy specimen in which he/she can assess the symmetry,
      circumscription, breadth, and depth of the lesion.

PMID- 10886268
TI  - Liposuction and surgical recontouring of the neck: a retrospective analysis.
AB  - BACKGROUND: With the advent of tumescent liposuction, many advances in cosmetic
      surgery have occurred. Liposuction of excess adipose tissue from the submental
      area, jowls, and neck, along with cold steel surgery, has become an attractive
      alternative to the facelift for cervicomental aesthetic surgery. OBJECTIVE: To
      describe new techniques for tumescent neck liposuction, platysma repair, and
      subcutaneous musculoaponeurotic system plication, evaluate results, and assess
      complications with the procedures. METHODS: We reviewed the results of the last
      35 patients who underwent neck liposuction, simultaneous platysma plication,
      subdermal CO2 laser resurfacing, and/or subcutaneous musculoaponeurotic system
      plication at our institution. RESULTS: Three of 35 patients (9%) experienced mild
      complications from the procedure. Two of the three complications (66%) were in
      patients who underwent subdermal and/or platysma laser resurfacing at the time of
      liposuction. Good to excellent results were achieved in 91% of patients and fair
      to good results were achieved in 9%. No major complications such as nerve injury
      occurred. CONCLUSION: Neck liposuction can be a safe method for facial
      rejuvenation when performed properly. Platysma repair, and in some cases
      subcutaneous musculoaponeurotic system plication, can further improve results
      when combined with the liposuction procedure.

PMID- 10886269
TI  - Long-term evaluation of the long-pulsed alexandrite laser for the removal of
      bikini hair at shortened treatment intervals.
AB  - BACKGROUND: Laser-assisted hair removal is becoming the treatment of choice for
      removing unwanted hair. OBJECTIVE: The purpose of this work was to determine the
      long-term efficacy of the long-pulsed infrared (LPIR) laser at shortened
      treatment intervals for the treatment of bikini hair. METHODS: Eleven patients
      received five treatments at 3-week intervals to the right groin using the LPIR
      laser. Laser parameters were held constant for all treatments: 10 mm spot size,
      20 J, and 20-msec pulse duration. Results were evaluated 1 year after the last
      laser treatment. Hair counts were performed. RESULTS: The average patient had a
      78% clearance of hair noted at 1 year with no evidence of scarring or pigmentary
      changes. CONCLUSIONS: A simulated model of cutaneous hair follicles provides
      evidence that shorter treatment intervals (3 weeks) may be preferable for more
      complete destruction of the hair follicle bulb and bulge.

PMID- 10886270
TI  - Long-term results of wide surgical excision in 106 patients with hidradenitis
      suppurativa.
AB  - BACKGROUND: Hidradenitis suppurativa (acne inversa) is a chronic recurrent
      disorder characterized by abscessing inflammation, fistulating sinus tracts, and
      scarring. Predilection sites are the intertriginal regions. The severe course of
      the disease demands an early and curative treatment. OBJECTIVE: The aim of this
      study was to review the effect of radical surgical excision concerning cure rate
      and potential complications within a large group of patients. METHODS: We
      analyzed data for 106 patients suffering from hidradenitis suppurativa treated
      during the period 1980-1998. The mean duration of the disease was 7 years. In
      about 90% of the cases, two or more sites were affected. Inguinal (70.8%) and
      axillary regions (61.3%) were most commonly involved. All patients were treated
      by radical wide excision using intraoperative marking of sinus tracts with
      methylviolet solution. The method of reconstruction depended on the size and
      location of the defect. Median postoperative follow-up time was 36 months.
      RESULTS: The overall complication rate was 17.8%. Most of these were minor
      complications such as suture dehiscence, postoperative bleeding, and hematoma.
      Wound infection occurred in only 3.7% of patients. The rate of recurrence within
      the operated fields was 2.5%. There was no relation between the surgical method
      of reconstruction and the rate of recurrence. Recurrence was related to the
      severity of the disorder. CONCLUSION: Our results confirm early radical excision
      as the treatment of choice for hidradenitis suppurativa. Using intraoperative
      color-marking of sinus tracts, the recurrence rate is minimal. The method of
      reconstruction has no influence on recurrence and should be chosen with respect
      to the size and location of the excised area.

PMID- 10886271
TI  - Quantitative assessment of superficial venous insufficiency using duplex
      ultrasound and air plethysmography.
AB  - OBJECTIVE: The purpose of this study was to quantitatively evaluate venous reflux
      in limbs with isolated superficial venous insufficiency using color duplex
      ultrasound. In addition, air plethysmography (APG) was used to investigate
      possible correlations of duplex-derived peak velocity, duration of reflux, and
      CEAP classification. METHODS: One hundred and forty-six legs in 109 patients with
      isolated superficial venous insufficiency refluxing throughout the length of the
      limb were selected for prospective study by duplex scan. Reflux was defined as
      duration of reflux >/=0. 5 seconds. This study was conducted in a university
      hospital. Venous reflux was evaluated with the patients standing, by the duration
      of reflux, retrograde peak velocity, reflux volume at the saphenofemoral and
      saphenopopliteal junction as well as the greater saphenous vein in the thigh.
      Values obtained by APG were the venous volume (VV), venous filling index (VFI),
      ejection fraction (EF), and residual venous fraction (RVF). A significant
      difference was defined as P <.05. Three groups of limbs were analyzed: group A
      limbs with a retrograde peak velocity greater than 30 cm/second and a duration of
      reflux of less than 3 seconds; group B with a retrograde peak velocity >/=30
      cm/second and a duration of more than 3 seconds; and group C with a retrograde
      peak velocity of less than 30 cm/second and a duration of reflux of more than 3
      seconds. RESULTS: Groups A and B contained 103 limbs, and 24 of these were in
      CEAP class 5 and 6. Group C contained 43 limbs, none of which were in class 5 or
      6. APG demonstrated significant reflux in group A, and VFI was significantly
      higher compared to group B and group C (P =.0007 and P =.0064, respectively). A
      significant correlation was demonstrated between peak retrograde reflux velocity
      and VFI. CONCLUSIONS: Severe chronic venous insufficiency is found in limbs with
      high reflux velocity (greater than 30 cm/second) and the duration of reflux does
      not correlate with severe chronic insufficiency.

PMID- 10886272
TI  - Oral isotretinoin as part of the treatment of cutaneous aging.
AB  - BACKGROUND: A number of drugs have been used to prevent aging changes. However,
      studies of oral isotretinoin, the commonly used acne drug, as an antiaging drug
      are lacking. OBJECTIVE: To determine improvement in cutaneous aging utilizing
      oral isotretinoin combined with different procedures of facial rejuvenation.
      METHODS: Sixty patients ranging in age from 35 to 65 years, in whom additional
      modalities of rejuvenation were also used, were randomly assigned to receive
      treatment with oral isotretinoin (10-20 mg three times a week for 2 months, group
      A). Their results were compared with 60 patients who had undergone the same
      surgical procedures but with no oral isotretinoin (group B). RESULTS: All
      patients treated with oral isotretinoin noted improvement in wrinkles, thickness
      and color of the skin, size of pores, skin elasticity, tone, and reduction in
      pigmented lesions and mottled hyperpigmentation. A statistically significant
      difference was found in the improvement of group A (Wilcoxon test <0.01). Using
      minimal amounts of this drug, the side effects were practically negligible.
      CONCLUSION: Utilizing various procedures with oral isotretinoin allowed us to
      improve the effects of cutaneous aging. Our results using isotretinoin in these
      cases have been satisfactory. We believe that this is one of the first reports of
      the use of oral isotretinoin in intrinsic and photoaged skin.

PMID- 10886273
TI  - Q-switched ruby laser treatment for postsclerotherapy hyperpigmentation.
AB  - BACKGROUND: One of the most common adverse sequelae of sclerotherapy is cutaneous
      hyperpigmentation. OBJECTIVE: We used the Q-switched ruby laser to treat
      postsclerotherapy hyperpigmentation. METHODS: Eight patients developed
      pigmentation lasting more than 1 year (1-2 years on average) after sclerotherapy
      treatment for reticular and telangiectatic veins in the legs ranging in size from
      0.2 to 4 mm in diameter. All patients were treated with a Q-switched ruby laser
      at 694 nm, 4 mm beam size, and fluence range of 5.6-10.5 J/cm2. RESULTS: Ninety
      two percent of lesions lightened after treatment. There was significant (75-100%)
      resolution of hyperpigmentation in 58% of treated areas, 25% improvement in 33%
      of treated areas, and no improvement in the remaining areas. CONCLUSION: Our
      impression is that given a choice of lasers, the Q-switched ruby laser provides
      the greatest efficacy for treating postsclerotherapy hyperpigmentation.

PMID- 10886274
TI  - The use of variable pulse width frequency doubled Nd:YAG 532 nm laser in the
      treatment of port-wine stain in Chinese patients.
AB  - BACKGROUND: Variable pulse width frequency doubled Nd:YAG 532 nm laser has
      previously been shown to be effective in the treatment of vascular lesions in
      Caucasians. For dark-skinned patients, such as Asians, its role has not been
      determined. OBJECTIVE: To assess the clinical efficacy and complication rate of
      the 532 nm Nd:YAG laser in the treatment of port-wine stain in Chinese patients.
      METHODS: Chinese patients with port-wine stain who had undergone Nd:YAG laser
      treatment were called for questionnaire assessment of their degree of clearing
      and clinical examination for complications by two independent observers. For 22
      patients with pre- and posttreatment photographs, the two independent observers
      further assessed the degree of clearing. RESULTS: Assessment of the questionnaire
      indicated that 62.9% of the patients subjectively considered that they had more
      than 25% clearing, with 33.3% having more than 50% clearing. For those with pre-
      and posttreatment photographs, the objective degree of improvement was less
      impressive with 18.1% of patients having at least 25% improvement and only 13.6%
      having more than 50% improvement. Pigmentary and texture changes were seen in
      both groups (33% in group I and 11% in group II). The number of treatment
      sessions rather than previous use of pulsed dye laser therapy was an important
      risk factor for complications. CONCLUSION: Nd:YAG laser is only partially
      effective for the treatment of port-wine stain in Chinese patients. Although most
      patients recorded some degree of subjective improvement, many did not improve by
      objective assessment. High fluence is necessary to achieve the desirable clinical
      response, and while contact cooling reduces the risk of epidermal damage, texture
      changes can still occur. Further study is necessary to compare its use with other
      similar devices, such as a pulsed dye laser with cryogen spray cooling.

PMID- 10886275
TI  - Deep shave excision of macular melanocytic nevi with the razor blade biopsy
      technique.
AB  - BACKGROUND: Shave excision is an established surgical method for removing benign
      skin lesions for cosmetic and functional reasons. Usually superficial shave
      excision is performed with a common scalpel blade for the removal of papular
      nevi. However, there is little known about deep shave excision of macular
      melanocytic nevi with the razor blade technique. OBJECTIVE: The present study was
      undertaken to evaluate the cosmetic outcome of deep shave excision of macular
      melanocytic nevi with the razor blade technique. Moreover, its potency for
      sufficient removal of these lesions was investigated. METHODS: Within routine
      skin cancer screening 45 outpatients with a total of 77 macular melanocytic nevi
      were prospectively recruited. Deep shave excisions of these lesions were
      performed with a double-edged razor blade followed by chemical hemostasis.
      Histologically all specimens were processed and evaluated in a routine manner.
      After 6 months the physician and patients evaluated the shave sites for cosmetic
      outcome with a score graded from 1 to 4 (1 = excellent; 2 = good; 3 = moderate; 4
      = poor). RESULTS: Histologically 88% (68 of 77) of the melanocytic lesions were
      described as completely excised and 60% (46 of 77) were diagnosed as atypical
      melanocytic nevi; 12% (9 of 77) of the nevi were incompletely excised on the
      depth. On average, the deep margin of the specimens (n = 77) was 0.5 mm (range 0
      1.8 mm) and the lateral margin was 2 mm (range 0.3-8.2 mm). After 6 months 56
      shave sites could be reassessed. We observed mild hypopigmentation in 52% (29 of
      56), hyperpigmentation in 32% (18 of 56), and erythema in 23% (13 of 56).
      Recurrent nevi occurred in 13% (7 of 56). The evaluation of the cosmetic outcome
      by the patients (mean score 1.7) achieved better results than the evaluation by
      the physician (mean score 2.5). The cosmetic results showed no significant (P
      >.05) differences in various anatomic sites. CONCLUSION: Our data confirm that
      deep razor blade excision presents a highly useful and inexpensive method for the
      removal of macular melanocytic nevi that yields adequate specimens for pathologic
      interpretation. We consider that shave excision with the razor blade technique is
      potentially much less scarring than full-thickness scalpel excisions of nevi. In
      particular, this is of great significance for patients with multiple nevi, such
      as dysplastic nevi syndrome.

PMID- 10886276
TI  - Topical anesthesia for laser hair removal: comparison of spot sizes and 755 nm
      versus 800 nm wavelengths.
AB  - BACKGROUND: The Candela alexandrite and the Coherent diode laser systems come
      equipped with built-in skin cooling systems that are designed to both protect the
      epidermis, allowing higher fluences, and to alleviate discomfort. Nevertheless,
      pain can be a significant problem especially with treatment of larger areas.
      Scatter of the laser beam is reportedly affected by the spot size. It is claimed
      that larger spot sizes are more effective at identical fluences. OBJECTIVE: This
      study evaluated the effectiveness of a topical 5% lidocaine cream (ELA-Max) to
      control pain and compared pain levels at identical fluences between the 8 mm and
      12 mm spot size of the alexandrite laser and between the alexandrite and diode
      laser with its 9 mm spot size. METHODS: The study was conducted in the axillae of
      12 patients. Each axilla was divided in half for side-by-side comparison. Half of
      the right axilla was treated with the alexandrite 8 mm and the other half with
      the 12 mm spot size at identical fluences. The left axilla was treated at the
      maximum tolerated fluences with the alexandrite 12 mm spot size and the diode 9
      mm spot size. RESULTS: At identical fluences and other parameters, there was
      significantly more pain with the alexandrite 12 mm spot size than with the
      alexandrite 8 mm spot size, both with or without topical anesthesia. The
      alexandrite laser was significantly less painful than the diode laser both with
      and without topical anesthetic. The difference was most noticeable between the
      alexandrite 8 mm spot size and the diode 9 mm spot size. Topical 5% lidocaine
      anesthesia was effective in reducing pain, though not completely, for both the
      alexandrite and the diode lasers. CONCLUSION: Topical 5% lidocaine cream is a
      simple and effective method for reducing patient discomfort during laser hair
      removal procedures, even when a skin cooling device is being used. A larger spot
      size causes more pain than a smaller spot size at identical fluences. The 800 nm
      diode laser causes greater discomfort than the 755 nm alexandrite laser.

PMID- 10886277
TI  - Utility of rush paraffin-embedded tangential sections in the management of
      cutaneous neoplasms.
AB  - BACKGROUND: Mohs micrographic surgery (MMS) modified by the use of tangential,
      formalin-fixed, paraffin-embedded histologic specimens is advantageous in
      treating selected skin neoplasms. OBJECTIVE: To review the use of our experience
      with a modification of MMS to treat lentigo maligna melanoma (LMM), lentigo
      maligna (LM) and other melanoma in situ (MIS) lesions, dermatofibrosarcoma
      protuberans (DFSP), atypical fibroxanthoma (AFX), and angiosarcoma. METHODS: Our
      experience utilizing a modification of MMS in the treatment of 77 patients with
      LM or other MIS, 23 patients with LMM, 11 patients with DFSP, 1 patient with AFX,
      and 1 patient with angiosarcoma was reviewed. Length of follow-up and rate of
      recurrence were examined. A literature review of this pertinent modification of
      the Mohs technique was performed. RESULTS: One hundred fourteen patients
      underwent MMS for melanocytic (LM, MIS, LMM), spindle cell (DFSP, AFX), and
      vascular malignant neoplasms. One patient developed locally recurrent LM and one
      patient with LMM developed satellite metastasis. Regional lymph node metastasis
      occurred in one patient with LMM and in a patient with angiosarcoma. CONCLUSION:
      The use of Mohs micrographic surgery in conjunction with rush formalin-fixed,
      paraffin-embedded tangential histologic sections provides the accuracy and tissue
      conservation of the Mohs procedure while ensuring more confident interpretation
      of histology in cases of lentigo maligna, lentigo maligna melanoma,
      dermatofibrosarcoma protuberans, atypical fibroxanthoma, and angiosarcoma.

PMID- 10886278
TI  - Female androgenetic alopecia: a separate entity.
AB  - BACKGROUND: It has always been assumed that female AGA represents the female
      counter part to male AGA. OBJECTIVE: To present arguments illustrating that these
      are entirely different entities. METHOD: Four well-known facts about both
      entities that would indicate they are separate are cited. Family pedigree filled
      with female AGA and minimal male AGA is presented and a reference to a female
      with no curculating androgens and typical female AGA is cited. RESULTS AND
      CONCLUSION: Based on evidence presented it is concluded these are two entirely
      different diseases.

PMID- 10886279
TI  - Stasis in venous ulcers: a misnomer that should be abandoned.
AB  - Leg ulcerations secondary to chronic venous insufficiency have been termed
      'stasis ulcers.' This is based on an original idea proposed by Homans in 1917.
      However, since then data has been generated suggesting in fact 'stasis' does not
      occur. In this paper, we review the information that has accumulated, refuting
      the concept of stasis. We suggest that the term 'stasis ulcer' is a misnomer, and
      should be abandoned.

PMID- 10886280
TI  - Recurrent clear cell hidradenoma of the foot.
AB  - BACKGROUND: Clear cell hidradenoma is an uncommon neoplasm without established
      optimal treatment. OBJECTIVE: Using Mohs micrographic surgery, a recurrent clear
      cell hidradenoma of the right foot was treated. METHODS: Case report and
      literature review. RESULTS: Two stages of Mohs micrographic surgery and
      subsequent repair successfully treated the recurrent clear cell hidradenoma. No
      recurrence of the neoplasm has been observed at 11 months follow-up. CONCLUSION:
      Optimal treatment of clear cell hidradenoma is unestablished. Adequate primary
      local excision is essential. Mohs micrographic surgery should be considered for
      treatment, especially on recurrent tumors in critical locations.

PMID- 10886281
TI  - Utility of a bilayered banner transposition flap in reconstruction of the lower
      third of the pinna.
AB  - BACKGROUND: Reconstruction of the entire ear lobule is challenging and complex.
      We present a case in which a banner transposition flap from the preauricular and
      mandibular area of the cheek resulted in an excellent cosmetic outcome.
      OBJECTIVE: To demonstrate the utility of a bilayered banner transposition flap to
      reconstruct a full-thickness defect of the inferior one-third of the pinna.
      METHODS: The technique employed in this reconstruction is described and
      previously reported techniques are reviewed. RESULTS: A symmetrical earlobe with
      normal tissue consistency was created, as noted at 4 months postoperatively.
      CONCLUSION: Utilization of a banner transposition flap should be considered as an
      excellent method for reconstruction of full-thickness defects of the lower one
      third of the ear.

PMID- 10886282
TI  - Multi-injection plate for intralesional corticosteroid treatment of patchy
      alopecia areata.

PMID- 10886283
TI  - Digital computerized mapping in Mohs micrographic surgery.

PMID- 10886284
TI  - Antibiotic prophylaxes in laser resurfacing patients.

PMID- 10886285
TI  - Against antibiotic prophylaxis for cutaneous laser resurfacing.

PMID- 10886286
TI  - Repair of a large surgical defect involving the upper lip and medial cheek.

PMID- 10886287
TI  - Suction device for epidermal grafting in vitiligo: employing a syringe and a
      manometer to provide an adequate negative pressure.
AB  - BACKGROUND: Suction devices for epidermal grafting need a suction pump to provide
      a negative pressure. The authors have developed a suction device in which a
      syringe and a manometer are employed to provide a negative pressure. OBJECTIVE:
      The purpose of this study was to evaluate the efficacy of our suction device in
      vitiligo patients. METHODS: The suction device was used to obtain epidermal
      blisters from the donor site. A CO2 laser was employed to remove the depigmented
      epidermis. The blister roofs of the donor site were harvested and were placed
      onto the recipient area. Ten patients with stable vitiligo were treated by
      epidermal grafting. RESULTS: Epidermal blisters were produced by suction in all
      patients. Also, all 10 patients regained repigmentation. CONCLUSION: Our suction
      blister device is simple and inexpensive to make, and it may become an
      alternative to the other suction devices.

PMID- 10886288
TI  - New technique in producing sclerosing foam in a disposable syringe.

PMID- 10886289
TI  - Lessons on dermoscopy #5.

PMID- 10886291
TI  - Clarification.

PMID- 10886290
TI  - Organization of a specialty clinic to optimize the care of organ transplant
      recipients at risk for skin cancer.

PMID- 10886292
TI  - The European Society of Anaesthesiologists and the EJA: strength in unity.

PMID- 10886293
TI  - Role of neuropeptides in heart failure: preliminary information or knowledge?

PMID- 10886294
TI  - On the search for the osteoporosis genes: how many more do we need?

PMID- 10886295
TI  - Somatic war syndromes: no man's land between the trenches?

PMID- 10886296
TI  - Neuropeptide variability in man.
AB  - BACKGROUND: Previous studies have established short-term variability in the
      circulating plasma levels of cardiac peptides such as atrial natriuretic peptide
      (ANP) and brain natriuretic peptide (BNP). Our aim was to investigate whether
      such variable patterns could be observed in other vasoactive peptides. METHODS:
      We measured the immunoreactivity of vasoactive intestinal polypeptide (VIP),
      neuropeptide Y (NPY), endothelin-1 (ET-1) and calcitonin gene-related peptide
      (CGRP) in peripheral venous plasma collected at 2-min intervals over a 20-min
      period from patients with chronic cardiac failure (CCF) and from control
      subjects. In a second study, blood samples were obtained at 2-min intervals from
      the pulmonary artery, femoral artery and antecubital vein from patients with
      normal cardiac function while right atrial pressure and heart rate were constant.
      RESULTS: Peripheral blood VIP, NPY and ET-1 had peaks and troughs (levels > 2SD
      from the mean) in both patients and controls, with approximate intervals of 10
      min. Levels of CGRP showed little variation. The overall levels [median (range);
      pmol L-1] of VIP [patients 27 (2.1-85.5); controls 9.8 (0-34)] and NPY [patients
      20 (0-110); controls 12 (5-19)] were higher in patients (P < 0.05). Circulating
      plasma levels of ET-1 and CGRP were about the same in both groups [ET-1: patients
      18 (2-84); controls 18 (0-48); CGRP: patients 4 (1-18.5), controls 5.5 (1-15); P
      = NS]. Levels of CGRP, VIP and ET-1 were similar in the pulmonary and femoral
      arteries, whereas systemic arterial levels of NPY were higher than in the
      pulmonary artery. CONCLUSIONS: The data demonstrate marked variability in
      circulating levels of the neuropeptides studied. In addition, peaks and troughs
      were observed every 10-15 min from all three vascular beds. If these peptides are
      secreted in a pulsatile pattern, then interpretations of single measurements
      should be guarded. Furthermore, this study raises interesting questions about the
      physiology of hormone secretion in man.

PMID- 10886297
TI  - Postprandial response to a fat tolerance test in young adults with a paternal
      history of premature coronary heart disease - the EARS II study (European
      Atherosclerosis Research Study).
AB  - BACKGROUND: The European Atherosclerosis Research Study (EARS) I had shown that
      fasting plasma concentrations of apolipoprotein B (apo B) and triglycerides were
      the most discriminant variables between offspring with a paternal history of
      coronary heart disease (CHD) and controls. The EARS II study was undertaken to
      investigate whether a paternal history of CHD was associated with differences in
      postprandial lipemia. DESIGN: Male subjects with a paternal history of CHD
      (cases, n = 407) and age-matched male controls (n = 415) were recruited from 14
      European universities. All subjects had an oral fat tolerance test. RESULTS: In
      the sample as a whole, the postprandial triglyceride responses did not
      significantly differ between the two groups. However, in the upper tertile of
      fasting triglycerides, cases displayed a higher area under the curve (5.71 vs.
      4.49 mmol.h L-1, P < 0.001), a higher peak (1.76 vs. 1.43 mmol L-1, P < 0.001)
      and a more delayed time to peak (3.15 vs. 2.91 h, P < 0.05) than controls. In the
      upper tertile, fasting apo B levels (P < 0.05) and triglyceride area under the
      curve (P = 0.002) significantly discriminated cases from controls in a
      multivariate analysis. Cases had also higher Lp C-III:B levels at 4 h than
      controls (11.2 vs. 9.9 mg dL-1, P < 0.01) and this difference remained
      significant after adjustment for apo B and triglyceride levels. CONCLUSIONS:
      These results indicate that in subjects with a moderate elevation of fasting
      triglycerides, an impaired postprandial response to a fat load constitutes an
      early biological expression of a paternal history of premature CHD.

PMID- 10886298
TI  - Amelioration of hyperglycemic and hyperosmotic induced vascular dysfunction by in
      vivo inhibition of protein kinase C and p38 MAP kinase pathway in the rat
      mesenteric microcirculation.
AB  - BACKGROUND: Recently, we demonstrated in vivo effects of acutely induced
      hyperglycemia, diabetes and mannitol infusions on rat mesenteric microcirculation
      concerning leukocyte-endothelial-cell interaction (Schaffler et al. EJCI 28: 886
      893, 1998). DESIGN: In this study we have investigated the possible involvement
      of the protein kinase C (PKC) and p38 MAP kinase cascade as signal transducing
      elements during hyperglycemic and osmotic stress in an in vivo rat model.
      RESULTS: Acutely induced hyperglycemia resulted in a significant increase in
      leukocyte adhesion. This effect could be mimicked by mannitol. Both PKC and p38
      MAP kinase were involved in the effects mediated by glucose and mannitol. Acutely
      induced hyperglycemia resulted in a significant increase in leukocyte emigration.
      This effect could be imitated by mannitol. However, PKC and p38 MAP kinase were
      only involved under osmotic stimulation. The hyperglycemia-induced reduction in
      leukocyte rolling velocity seemed to be a glucose-specific effect, since mannitol
      did not influence leukocyte rolling velocity. This glucose effect on leukocyte
      rolling velocity was mediated by an activation of the PKC/p38 MAP kinase cascade.
      Both hyperglycemia and osmotic stimuli alone were able to reduce venular shear
      rate without recruitment of the p38 MAP kinase cascade. The observed reduction of
      shear rate seems to be mediated only by the osmotic effects of glucose via
      activation of the PKC system. CONCLUSION: The observed effects of glucose on
      adhesion, emigration and shear rate are due to osmotic effects. The PKC/MAP
      kinase cascade is involved as a signal transducing component. The reduction of
      leukocyte rolling velocity is a glucose-specific effect, mediated by the
      activation of both the PKC and the p38 MAP kinase cascade. Venular shear rate and
      leukocyte emigration can be influenced by glucose and mannitol due to different
      regulation mechanisms. It is concluded, that isoform-specific inhibitors of PKC
      and specific MAP kinase inhibitors represent a potential drug target for
      preventing microvascular dysfunction in diabetes.

PMID- 10886299
TI  - The expression of OX40 in immunologically mediated diseases of the
      gastrointestinal tract (celiac disease, Crohn's disease, ulcerative colitis).
AB  - BACKGROUND: The membrane bound receptor OX40 (CD134) - a member of the TNF-R/NGF
      R superfamily - is expressed on activated CD4+-T cells in humans and rodents. The
      interaction of OX40 with its ligand (OX40L) has been shown to be important in T
      cell dependent B cell-stimulation and T-cell costimulation in vitro and in vivo.
      Several studies in experimental animal models for immunologically mediated GI
      diseases have stressed the important role of the OX40-OX40L interaction for their
      manifestations. To assess if the OX40-OX40L interaction is also crucial in the
      pathogenesis of immunologically mediated diseases of the human gastrointestinal
      tract (e.g. celiac disease, Crohn's disease, ulcerative colitis) we investigated,
      in a first line of experiments, the expression of OX40 in biopsy specimens of
      patients suffering from these diseases. METHODS: The biopsies were formalin fixed
      and paraffin-embedded and cut into 5 microm slides. To demask the antigen, the
      slides were consecutively cooked in citrate buffer for 20 min. Binding of anti
      OX40 antibody was detected using the alkaline phosphatase-anti-alkaline
      phosphatase (APAAP) method. RESULTS: Nine of 11 biopsy specimens of patients with
      celiac disease were OX40-positive; none of the 20 control duodenal biopsies
      demonstrated OX40-positivity; and all biopsies of patients with ulcerative
      colitis (n = 11) or Crohn's disease (n = 11), respectively, stained positively
      for OX40. One of the 20 control biopsies showed OX40 staining. DISCUSSION: OX40
      is highly expressed in the gastrointestinal tissue of patients with
      immunologically mediated bowel diseases. Together with previous studies in animal
      models for these diseases, the present results point to a potential role of OX40
      in their pathogenesis.

PMID- 10886300
TI  - [11C]Hyaluronan uptake with positron emission tomography in liver disease.
AB  - BACKGROUND: A hyaluronan-loading test has been developed for assessment of
      hyaluronan kinetics and applied in patients with liver and joint diseases. This
      test describes the metabolic process of hyaluronan but cannot define the specific
      contribution of different organs. A method for labelling of hyaluronan with the
      short-lived positron-emitting radionuclide 11C has been published and in this
      study applied in healthy subjects and liver diseases. MATERIALS AND METHODS:
      Positron emission tomography (PET) was used for the regional assessment and
      quantification of [11C]hyaluronan uptake in three healthy subjects, four patients
      with alcoholic liver cirrhosis, one with alcoholic hepatitis and one with liver
      steatosis. After intravenous administration of 60 MBq of 11C-labelled hyaluronan,
      a 55-min PET scan was performed over the liver and plasma radioactivity was
      analysed. Rate constants describing the transport of the [11C]hyaluronan tracer
      from plasma to the liver were calculated. RESULTS: High uptake was observed in
      the liver combined with a rapid elimination of tracer from plasma. The liver
      uptake rate (k1) was significantly lower in patients (0.018 min-1) than in
      healthy subjects (0.043 min-1, P = 0.002). The rate constants seem to be related
      to the severity of the disease as defined by the Child-Pugh score. CONCLUSIONS:
      The study suggests that PET with [11C]hyaluronan could be an accurate method by
      which to assess liver dysfunction, in conditions where endothelial cell function
      is impaired. The possibility of quantification over extended portions of the body
      also opens up possibilities to explore regional differences in liver function and
      to assess other elimination routes of hyaluronan.

PMID- 10886301
TI  - Polymorphisms in the vitamin D receptor gene and bone mass, bone turnover and
      osteoporotic fractures.
AB  - BACKGROUND: Vitamin D is essential for normal bone metabolism. Polymorphisms in
      exon 2, intron 8 and exon 9 of the vitamin D receptor (VDR) gene have previously
      been found to be associated with bone mass and bone turnover. MATERIALS AND
      METHODS: We examined the effect of these polymorphisms, separately and in
      combination, on bone mineral density (BMD), bone turnover, and the prevalence of
      osteoporotic fractures in 192 osteoporotic patients and 207 normal controls. The
      four polymorphisms were determined by RFLP using Fok I (T2-C), Bsm I (intron 8),
      Apa I (intron 8) and Taq I (T1055-C) after PCR. RESULTS: We did not find any
      association between the Fok I polymorphism and bone mass, bone turnover or
      prevalence of osteoporotic fractures. We found that BB + Bb-genotypes were more
      frequent in patients with osteoporotic fractures (chi2 = 3.50, P = 0. 06).
      Furthermore, BMD of the intertrochanteric region (P < 0.0001, ANOVA) as well as
      the total hip (P < 0.01, ANOVA) were higher in individuals with the bb-genotype.
      The Apa I and the Taq I polymorphisms were not distributed differently among
      osteoporotic patients and normal controls. Apa I was not associated with
      differences in BMD. BMD of the intertrochanteric region was higher in individuals
      with the TT-genotype compared with individuals with the Tt- or tt-genotypes (P <
      0.01, ANOVA), while no differences could be demonstrated in BMD of the lumbar
      spine, femoral neck, trochanter or Wards triangle. Combining the genotypes
      generally reflected the differences caused by the Bsm I polymorphism. CONCLUSION:
      We have found that the B-allele of the Bsm I polymorphism in the 3' untranslated
      region of the VDR was associated with low BMD at the hip, and tended to be
      associated with osteoporotic fractures. The translation initiation polymorphism
      in the VDR does not affect BMD and is not associated with osteoporotic fractures
      in men or women.

PMID- 10886303
TI  - Somatic hypotheses of war syndromes.
AB  - Since the end of the American Civil War, unexplained symptoms in military
      personnel arising after a war or peace mission have frequently been described.
      The pattern of symptoms is highly similar for all of the various war syndromes
      although the conditions of each war or peace mission are widely different. Many
      somatic hypotheses have been formulated to explain these syndromes; a
      considerable proportion of them are already outdated. In the last few years much
      attention has been given to Gulf War Syndrome and to unexplained symptoms of
      military personnel who were sent to Cambodia, Rwanda, Burundi, Zaire, or the
      former Yugoslavia. In this review the symptoms of war syndromes will be
      considered in more detail and the suggested somatic explanations will be
      discussed. During the last decade the following somatic causes have been
      suggested as possible explanations for these symptoms: (persistent) infection,
      abnormal immune response, administration of multiple vaccinations within a short
      period of time, use of malaria chemoprophylaxis, neurological abnormalities,
      exposure to toxicological substances and environmental factors. The various
      investigations performed to study these hypotheses are discussed. The fact that
      bias regularly occurs in the course of these investigations is pointed out. For
      the future, a reliable investigation of a war syndrome should be a prospective
      multidisciplinary study and should distinguish between causative and sustaining
      factors.

PMID- 10886302
TI  - Immortalisation of human bone marrow endothelial cells: characterisation of new
      cell lines.
AB  - BACKGROUND: Adhesion of haematopoietic progenitor cells (HPC) to human bone
      marrow endothelial cells (HBMEC) plays a key role in homing of HPC to bone
      marrow. Here we describe four new HBMEC cell lines that can be used to study the
      (specific) adhesion of HPC to HBMEC. DESIGN: HBMEC were immortalised with a
      retroviral construct containing the human papilloma virus 16 E6/E7 genes. Four
      cell lines were characterised. RESULTS: The cell lines showed their endothelial
      nature by the expression of von Willebrand Factor and VE-cadherin (CD144).
      Electron microscopic analysis revealed normal endothelial-cell characteristics,
      including the presence of Weibel-Palade bodies and intercellular junction
      structures. An extensive phenotypic analysis of the cell-lines was performed,
      they were found to resemble primary HBMEC. The only difference found was the
      absence of expression of E-selectin (CD62e) and VCAM-1 (CD106) on resting HBMEC
      cell lines. Upon stimulation with IL-1beta the expression of E-selectin, VCAM-1
      and ICAM-1 (CD54) was upregulated. All resting cell lines bound CD34+ HPC.
      Adhesion was increased by addition of the phorbol ester PMA. Two cell lines
      showed increased binding upon IL-1beta prestimulation. Highest adhesion was
      observed after the combination of IL-1beta prestimulation of the endothelial
      cells and addition of PMA. Binding of CD34+ HPC to HBMEC was compared with the
      binding to human umbilical vein endothelial cell lines and to a human dermal
      microvascular endothelial cell line (HMEC-1). So far, we have only found
      relatively less binding of HPC to IL-1beta prestimulated HMEC-1 cells, which
      could be explained by a reduced induction of E-selectin and VCAM-1 upon IL-1beta
      stimulation of these cells. CONCLUSION: The immortalised HBMEC cell lines have
      maintained their normal phenotype for the majority of characteristics examined.
      The expression of E-selectin and VCAM-1, which are not constitutively expressed
      on the cell lines, can be induced by stimulation of the endothelial cells with IL
      1beta. The cell lines have furthermore maintained their capability to bind HPC.
      They will therefore be useful to investigate the interactions between HPC and
      HBMEC involved in homing of HPC.

PMID- 10886304
TI  - Low levels of colonic glutathione S-transferase in patients with X-linked
      agammaglobulinaemia.
AB  - BACKGROUND: Patients with X-linked agammaglobulinaemia, a primary
      immunodeficiency disorder, suffer from recurrent infections of the respiratory
      and intestinal tract. Rapidly progressive colorectal cancer was diagnosed in
      three unrelated young adults with X-linked agammaglobulinaemia. This finding
      implies a 30-fold increase of risk for this cancer in this patient group.
      Glutathione S-transferases are a family of biotransformation enzymes involved in
      the detoxification of cytotoxic and carcinogenic compounds, that may function in
      the prevention of carcinogenesis. We investigated the possible role of the
      glutathione S-transferase enzyme system in the apparently increased colorectal
      cancer risk in X-linked agammaglobulinaemia patients. MATERIALS AND METHODS: We
      analysed the glutathione levels and the glutathione S-transferase enzyme activity
      and iso-enzyme composition in normal colonic biopsies of eight X-linked
      agammaglobulinaemia patients, 25 patients with a recent history of colonic
      adenomas and 10 healthy volunteers. RESULTS: X-linked agammaglobulinaemia
      patients had significantly lower glutathione S-transferase enzyme activities at
      all sites in the normal colonic mucosa as compared to adenoma patients. In X
      linked agammaglobulinaemia patients the rectal glutathione S-transferase enzyme
      activity was lower than in the proximal colon and significantly lower as compared
      to controls. CONCLUSION: This lower glutathione S-transferase enzyme activity
      might play a role in the apparently increased colorectal cancer risk in X-linked
      agammaglobulinaemia patients, assuming that detoxification of carcinogenic
      compounds plays a role in the aetiology of colon cancer of these patients.

PMID- 10886305
TI  - Clinical importance of antibodies against platelet activating factor in
      antiphospholipid syndrome manifestations.
AB  - BACKGROUND: We assessed whether antibodies against platelet activating factor
      (PAF) are related to the presence of antiphospholipid syndrome (APS) clinical
      manifestations, in particular thrombosis, in patients with connective tissue
      diseases. MATERIALS AND METHODS: Anti-PAF, anticardiolipin (aCL), antibeta2
      glycoprotein I (antibeta2GPI) and antiphosphatidylcholine (anti-PC) antibodies
      were determined in 52 patients with APS, 29 patients with systemic lupus
      erythematosus (SLE) aCL but without APS, 30 patients with SLE without aCL, and 30
      patients with scleroderma. A new enzyme-linked immunosorbent assay (ELISA) was
      developed for determining anti-PAF antibodies in a bovine serum-free fashion.
      RESULTS: The ELISA showed high specificity. Homologous inhibition experiments
      showed 60-70% inhibition. Anti-PAF antibodies were found in 18/52 APS patients,
      10/29 SLE/aCL+ patients, 9/30 SLE/aCL- patients and 3/30 scleroderma patients.
      Anti-PAF antibodies were significantly associated with anti-PC antibodies (odds
      ratio [OR] 12. 7, P < 0.01), and there was a modest association with
      immunoglobulin G (IgG) aCL (OR 3.1, P > 0.10), but not with IgM aCL or
      antibeta2GPI. Three SLE/aCL+ patients and five SLE/aCL- patients had clinical
      manifestations characteristic of APS. All these patients had anti-PAF antibodies,
      while none had high titres of aCL or antibeta2GPI antibodies and only one had
      anti-PC antibodies. Among the combined APS and SLE groups, the presence of anti
      PAF antibodies was significantly associated with clinical manifestations which
      are characteristic of APS (OR 2.6, P = 0.02). The effect was independent of IgG
      aCL and antibeta2GPI antibodies. CONCLUSIONS: Anti-PAF antibodies are common in
      APS and SLE and comprise an independent factor for the development of thrombosis.
      Several patients experiencing thromboses have anti-PAF antibodies without other
      antiphospholipid specificities.

PMID- 10886306
TI  - Warning! Perfusion syringes may not be inert.

PMID- 10886307
TI  - Evidence-based pharmacological treatment of dementia.
AB  - The current literature on the pharmacological treatment of dementia was reviewed
      and the strength of evidence for the efficacy of each drug was categorized using
      an evidence-based approach. Acetylcholinesterase-inhibitors represent the only
      category of drugs with consistently demonstrable efficacy in well-designed
      studies of Alzheimer's disease, although the effect is not large. There is a lack
      of prospective, controlled, randomized studies for most of the nootropics.
      Epidemiological evidence suggests prophylactic effects of oestrogens and anti
      inflammatory agents, and a single large-scale trial suggests that long-term
      administration of vitamin E or selegiline may be associated with improved outcome
      in patients with Alzheimer's disease. A number of drugs were reported to be
      effective in the treatment of non-cognitive symptoms of dementia including
      classical and atypical neuroleptics, antidepressants and anticonvulsants. The
      evidence for efficacy, however, is not strong for the majority of these
      compounds.

PMID- 10886309
TI  - Researching a differential impairment of frontal functions and explicit memory in
      early Parkinson's disease.
AB  - An impairment at tasks sensitive to frontal lobe damage has been repeatedly
      reported in Parkinson's disease, but the exact nature of these deficits has not
      yet been clarified. Similarly, deficits of visuo-spatial functions have been
      frequently observed, but it is still debated whether verbal and visuo-spatial
      memory can be differentially affected. In this study we have compared the
      performance of 20 mild Parkinson's disease patients (I-II Hoehn and Yahr stage)
      and 18 matched normal controls, at tasks assessing frontal functions and explicit
      memory. We detected a selective deficit in set shifting and maintaining, without
      impairment in categorization and set formation. The lack of a selective increase
      in perseverative errors might indicate that perseverations either measure
      something different from set shifting or that they do not represent an index
      sensitive enough to set shifting impairment. Parkinson's disease patients were
      also significantly impaired at Raven's Progressive Matrices, a task assessing
      both frontal and visuo-spatial aspects. However, they did not show any
      differential impairment of visuo-spatial memory. Indeed, despite a trend of lower
      performance in visuo-spatial learning, memory performance of Parkinson's disease
      patients was significantly different from that of controls only at a free recall
      test which involved both verbal and visuo-spatial memory. We suggest the
      exploration of set shifting and maintaining to detect 'frontal' deficits in mild
      Parkinson's disease. We argue that Raven's Progressive Matrices is a valuable
      task for detecting subclinical cognitive deficits in Parkinson's disease, even if
      it does not show a specific profile of impairment in these patients. According to
      our results, a differential evaluation of verbal vs. visuo-spatial memory is not
      necessary in clinical practice, whilst free recall confirms its usefulness to
      detect subclinical impairments of memory functions.

PMID- 10886308
TI  - The apolipoprotein E epsilon4 allele and the response to tacrine therapy in
      Alzheimer's disease.
AB  - The objective of our study was to evaluate the effects of the apolipoprotein E
      (ApoE) phenotype and gender on the response to tacrine treatment in Alzheimer's
      disease (AD). ApoE phenotyping was performed on 76 patients treated with tacrine
      for AD. This group comprised 33 ApoE epsilon4 allele carriers (epsilon4+) and 43
      non-epsilon4 carriers (epsilon4-). Patients were treated blindly in relation to
      the ApoE phenotype, with incremental tacrine dosages ranging from 40 mg/day up to
      the highest dosage (160 mg) tolerated without side-effects. At least 6 weeks
      elapsed between each increase. Changes in the scores for the Alzheimer Disease
      Assessment Scale-Cognitive Component (ADAS-Cog) between baseline and each
      increment in dosage were assessed in the epsilon4- and epsilon4+ groups. The cut
      off point for being considered as responsive to tacrine treatment was a 4-point
      decrease in the ADAS-Cog score. There was no tendency for the epsilon4- carriers
      to respond better than the epsilon4+ carriers. When patients were stratified by
      gender, no differences were found between the effects of the treatment on men and
      women. Consequently, these results do not support the hypothesis that the ApoE
      phenotype and gender are predictors of the response to tacrine in AD patients.

PMID- 10886310
TI  - Closed- and open-loop handwriting performance in patients with multiple
      sclerosis.
AB  - Normal subjects use an open-loop motor control strategy in handwriting, but they
      are able to switch to closed-loop motor control when the demands on accuracy
      increase. These closed-loop handwriting movements of normal subjects resemble the
      inefficient movements found in writing-impaired patients. The hypothesis that
      such movement deficits may in fact reflect the use of a closed-loop strategy was
      tested in a group of writing-impaired patients with multiple sclerosis (MS). The
      handwriting movements of 10 MS patients and 20 control subjects were examined
      with a digitizing tablet. Three conditions were used: a standard writing task
      (expt 1), a closed-loop condition (expt 2), and an open-loop condition (expt 3).
      Individual stroke movements were analysed. Stroke duration and segmentation were
      increased for MS patients in the standard writing task. The same was found for
      control subjects when they wrote under closed-loop conditions. However, under
      open-loop conditions, the handwriting movements of the MS patients were as fast
      and fluent as that of control subjects. The results support the hypothesis that
      the movement characteristics of the writing-impaired MS patients reflect an
      inadequate use of a closed-loop motor control strategy.

PMID- 10886311
TI  - Immunological effects of oral high-dose methylprednisolone in acute optic
      neuritis and multiple sclerosis.
AB  - The immunological effects of high-dose methylprednisolone in attacks of multiple
      sclerosis and acute optic neuritis have only been examined in a few randomized,
      controlled trials. We studied immunological changes in 50 patients with optic
      neuritis or multiple sclerosis who underwent lumbar puncture before and 1 week
      after completing a 15-day course of oral high-dose methylprednisolone treatment.
      Treatment resulted in a decrease in the concentration of myelin basic protein, a
      decrease in the serum concentration of immunoglobulin G (IgG) and intrathecal IgG
      synthesis, an increase in the cerebrospinal fluid concentration of transforming
      growth factor-beta1, and changes in the expression of CD25, CD26, and human
      leukocyte antigen-DR (HLA-DR) on CD4 T-cells. No effect was seen on the
      cerebrospinal fluid leucocyte count or the cerebrospinal fluid activity of matrix
      metalloproteinase-9 (MMP-9). The lack of a persistent effect on cerebrospinal
      fluid leucocyte recruitment and MMP-9 activity, despite changes in IgG synthesis,
      T-cell activation, and cytokine production, suggests that modulation of the
      function of inflammatory cells may contribute to the clinical efficacy of oral
      high-dose methylprednisolone treatment in optic neuritis and multiple sclerosis.

PMID- 10886312
TI  - Increased T-lymphocyte interleukin-6 binding in patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) represents a T-cell-mediated autoimmune demyelinating
      disease of the central nervous system associated with altered immunoregulation.
      Interleukin (IL)-6 is a cytokine that has several effects on the neuroimmune
      system. Specific IL-6 receptors have been found in human lymphocytes and
      neuroglial cells. The aim of the present study was to assay IL-6 binding on
      peripheral blood T lymphocytes in MS patients. We found that T cells from MS
      patients had significantly more IL-6 receptors [Bmax: 279 +/- 7 vs. 246 +/- 8
      (mean +/- SEM) receptors/cell, in patients and controls, respectively], whereas
      Kd values were similar to those of healthy subjects [26.8 +/- 0.7 vs. 25.4 +/-
      0.6 (mean +/- SEM) pM, in patients and controls, respectively]. Significant (P <
      0.05) differences in IL-6 binding values were observed between stable patients
      and those relapsing (272 +/- 9 vs. 300 +/- 12 (mean +/- SEM) receptors/cell,
      respectively). We found significantly (P < 0. 001) higher amounts of IL-6
      receptors on CD4+ T cells from MS patients than on CD4+ lymphocytes from controls
      (434 +/- 11 vs. 363 +/- 9 (mean +/- SEM) receptors/cell, respectively); CD8+ T
      cells showed very few IL-6 receptors in both patients and controls. These data
      are discussed in terms of MS immune pathogenesis and pathophysiology, because T
      cell activation seems to be linked to increased IL-6 binding. The upregulated IL
      6 system might be involved in antibody-mediated demyelinating pathways, because
      IL-6 is well known to enhance humoral immune response.

PMID- 10886313
TI  - Unexpectedly severe sleep and respiratory pathology in patients with amyotrophic
      lateral sclerosis.
AB  - Daytime fatigue and sleep disturbance are frequent complaints in patients with
      amyotrophic lateral sclerosis (ALS). However, polysomnographic data are sparse.
      Nocturnal respiratory insufficiency may occur despite nearly normal daytime
      pulmonary function. We describe the clinical presentation and polysomnographic
      findings in two patients with clinically and electrophysiologically confirmed ALS
      with minimal weakness but excessive daytime sleepiness. Polysomnography in the
      first patient showed a respiratory disturbance index of 43.5, and profound oxygen
      desaturations to 62%. The second patient had prolonged periods of
      hypoventilation, with oxygen saturations oscillating between 86 and 83%. Both
      patients showed severe sleep maintenance insomnia with a sleep efficiency < 40%
      and frequent arousals while asleep. Application of continuous positive airway
      pressure (CPAP) restored normal nocturnal ventilation, blood oxygenation and
      sleep parameters in the first patient; compliance, however, was poor. The second
      patient was unable to tolerate CPAP. We conclude that ALS patients with excessive
      daytime sleepiness or insomnia should undergo polysomnography to adequately
      diagnose nocturnal respiratory insufficiency and sleep disturbance. Compliance
      with treatment, however, may be poor.

PMID- 10886314
TI  - Impaired interleukin-2 response of mononuclear cells in Guillain-Barre syndrome.
AB  - We studied the production of and response to interleukin-2 (IL-2) by cultured
      peripheral blood mononuclear cells (PBMC) and the soluble IL-2 receptor levels in
      10 patients with GBS (eight men and two women) aged 23-67 years. The first blood
      sample was obtained within seven days of the onset of neuropathic symptoms, and
      blood samples were collected serially after treatment with plasma exchange. PBMC
      from GBS patients were found to produce little IL-2 and to have a low response to
      IL-2 soon after the onset, but marked improvement was seen within one month,
      concomitantly with improvement of neuropathic symptoms. Serum soluble IL-2
      receptor levels were increased at the onset, but gradually decreased thereafter.
      Our findings suggest that primary immune response in acute-stage GBS may be
      downregulated via a decrease in the function of PBMC that had previously been
      activated by interacting with the antigen.

PMID- 10886315
TI  - Similarities and differences in the phenotype, genotype and pathogenesis of
      different spinocerebellar ataxias.
AB  - Historically, the differential diagnosis of the autosomal ataxias (ADCAs) has
      been difficult. In 1983 Harding proposed a useful clinical classification. Since
      1983 ADCAs have been increasingly characterized in terms of their genetic locus
      and are referred to as spinocerebeller ataxia (SCA). The overlap between the SCA
      phenotypes and the high variability within SCA subgroups means that, for
      individual patients, the underlying mutation cannot be predicted reliable purely
      on the basis of clinical symptoms and so diagnosis should be made on the
      genotype. However, for executing DNA analyses in order of clinical likelihood,
      neurologists may try to deduce the underlying mutation by using a clinical
      algorithm. In this article we not only describe such an algorithm but also plot
      the pathway from clinical presentation, genetic classification and mutation,
      abnormal protein to common neuropathology in these disorders.

PMID- 10886316
TI  - Phenomenological diversity of spinal reflexes in brain death.
AB  - In brain death, spinal reflexes and automatisms are observed which may cause
      irritation and even doubt in the diagnosis. In the literature there are no
      dedicated descriptions of the diversity and of neuroanatomical considerations. In
      278 examinations of 235 patients for the determination of brain death, on 42
      occasions obvious spinal reflexes and/or spinal automatisms were observed in 27
      brain dead bodies. Because they were not systematically searched for, minute
      forms have probably been missed. The reflexes (R) and automatisms (A) are
      described according to the time of observation in relation to the development of
      brain death, the presumable spinal localization and the possible phylogenetical
      interpretation. Especially disquieting examples are discussed in more detail,
      e.g. monophasic EndotrachealSuction-ThoracicContraction-R supposedly switched in
      segments C2-6 or TrapeziusPinch-ShoulderProtrusion-R conveyed by the accessory
      nerve (terminology according to the scheme: for the reflexes, Trigger-Response-R:
      for the automatisms, Movement-A). After these experiences a more thorough
      examination showed frequent observations of rather minute forms of spinal
      reflexes, as well as automatisms and even the Lazarus sign (in possibly more than
      two thirds of the examinations). An estimation of the factual frequency would
      necessitate special attention to those much more frequent but less obvious minute
      spinal reflexes and automatisms.

PMID- 10886317
TI  - Assessment of corticodiaphragmatic pathway and pulmonary function in acute
      ischemic stroke patients.
AB  - This study investigates the effect of stroke on the corticodiaphragmatic pathway
      and attempts to clarify the relationship between neurophysiological data and
      degree of motor disability, site of infarction in computerized tomography (CT)
      scan, diaphragmatic excursion, blood gases and pulmonary function in stroke
      patients. Using magnetic stimulation of the scalp sites and cervical roots, an
      assessment of corticodiaphragmatic pathway was made. The study included 34
      sequentially selected patients from a total of 250 patients with acute ischemic
      stroke. Twenty-five (age- and sex-matched) volunteers served as controls. Sixteen
      patients had cortical infarction, 13 had subcortical infarction and five had both
      cortical and subcortical infarction. The mean according to the Scandinavian
      Stroke Scale was 32.2. Decreased diaphragmatic excursion was observed in 41% of
      the patients. Twenty-four patients (70.5%) had abnormal magnetic evoked
      potentials (MEPs) in the affected hemisphere. In five patients MEPs could not be
      elicited from the affected hemisphere; the remaining 19 patients had abnormal
      values of both cortical latency and central conduction time (CCT). Cortical
      latency, CCT, amplitude of compound muscle action potentials (CMAPs) and
      excitability threshold of the affected hemisphere were significantly altered
      compared with both the unaffected hemisphere and the control group. Those
      patients with hemiplegia had a greater degree of hypoxia, hypocapnia and
      decreased serum bicarbonate level compared with the control group. Also,
      hemiplegic patients had different degree of respiratory dysfunction. A
      statistically significant association was found between neurophysiological data
      and disability score, diaphragmatic excursion, site of infarction in CT scan and
      degree of respiratory dysfunction. Central diaphragmatic impairment may occur in
      acute stroke and could contribute to the occurrence of hypoxia in those patients.

PMID- 10886318
TI  - Are periodic leg movements during sleep (PLMS) responsible for sleep disruption
      in insomnia patients?
AB  - On the basis of polygraphic findings, it has been suggested that periodic leg
      movements during sleep are not responsible for sleep impairment (Lugaresi et al.,
      1972). However, for some authors it is an important cause of insomnia
      (Guilleminault et al., 1975; Coleman, 1982). Thus, the relationship between
      periodic leg movements during sleep, sleep disruption and the complaint of
      patients is particularly complex. We investigated the macro- and micro-structure
      of sleep with and without leg movements in 10 PLMS patients complaining of
      insomnia to clarify whether periodic leg movements are responsible for sleep
      disruption. The total sleep time without periodic leg movements was significantly
      longer than sleep time with leg movements. Sleep time without leg movements was
      longer than sleep time with leg movements in stage 2, slow wave sleep (SWS) and
      rapid eye movement (REM) sleep. Short lasting awakenings were significantly more
      frequent during periodic leg movements associated sleep whilst long lasting
      awakenings were equally frequent during sleep with and without periodic leg
      movements. The percentage of the four electroencephalogram (EEG) activities
      (delta, theta, alpha and spindles) did not show any significant difference
      between periodic leg movements associated and not associated with sleep stages
      and total sleep time. The lack of significant differences in both the macro- and
      micro-structure of sleep and EEG activity content regarding the association with
      movements confirm the hypothesis that periodic leg movements did not primarily
      cause sleep disturbance.

PMID- 10886319
TI  - Apraxia of lid opening is alleviated by pallidal stimulation in a patient with
      Parkinson's disease.
AB  - Apraxia of lid opening (ALO) is a syndrome characterized by a non-paralytic
      inability to open the eyes at will in the absence of visible contraction of the
      orbicularis oculi muscle. Here we report that globus pallidus internus deep brain
      stimulation on the right side markedly alleviates ALO as well as gait freezing in
      a patient with Parkinson's disease.

PMID- 10886320
TI  - Olivopontocerebellar atrophy: paraneoplastic syndrome of brain tumour?
AB  - We describe a patient who, three years after the onset of an olivopontocerebellar
      atrophy, developed a right cerebral tumour. The cerebellar symptomatology also
      included, as in other cerebellar patients previously described, a peripheral
      dysgraphia. Because this deficit of writing is generally reported in patients
      with right cerebral lesion, the authors hypothesized that functional alterations
      of supratentorial structures preceding the tumour by years may be able to damage
      the neural substrates connecting cerebral and cerebellar structures and to
      produce cerebellar atrophy.

PMID- 10886321
TI  - Isolated, unilateral, reversible palsy of the hypoglossal nerve.
AB  - We report three patients with isolated unilateral hypoglossal nerve palsy who
      experienced an excellent outcome. In two patients no cause was found. Our study
      seems to confirm that the occurrence of benign and idiopathic isolated unilateral
      palsy of the hypoglossal nerve is more frequent than previously reported. We
      would like to stress that neuroimaging studies remain mandatory in order to
      exclude other common causes, such as tumour and spontaneous or traumatic vascular
      lesions, in which a specific treatment is necessary.

PMID- 10886322
TI  - Complex regional pain syndrome with selective emotional sudomotor failure.
AB  - We report a patient with sympathetically maintained pain following a mild limb
      injury. Only emotional sudomotor failure was found in the painful limb.
      Thermoregulatory vasomotor function was intact. However, the patient had other
      target-specific sympathetic lesions, including thermoregulatory vasomotor failure
      in a different limb, not associated with pain. We hypothesize that the
      sympathetic failure preceded the symptoms and that the mild injury may have
      provoked collateral sprouting of emotional sudomotor fibres, coupling them with
      somatic sensory fibres to cause continuous pain.

PMID- 10886323
TI  - Multimedia education in headache: the European Neurological Network.
AB  - The European Neurological Network is a European Economic Community supported
      project. The purpose of the project was to develop a multimedia educational tool
      for general practitioners in order to improve their management of sleep
      disorders, epilepsy and headache. The project involves approximately one hundred
      engineers and physicians from Belgium, Denmark, England, Finland, France,
      Germany, Italy, Portugal and Spain. This paper concerns the multimedia
      educational tool on headache. The system consists of five different modules, i.e.
      classification, clinical data, headache tutorial, diagnostic headache diary and
      nomenclature. It is possible to move between the modules both vertically and
      horizontally. The headache classification of the International Headache Society
      is provided in full text as a work of reference. This classification is used
      world wide and has been adopted by International Classification of Diseases 10
      Neurological Adaptation (ICD-10 NA) and the World Health Organisation. The
      clinical data concentrate on migraine and tension-type headache, the two most
      common headache disorders, but data on familial hemiplegic migraine, cluster
      headache, drug-induced headache and secondary headaches are also available. The
      headache tutorial consists of case records that the user can test their
      diagnostic abilities on. The diagnostic headache diary is an expert system on
      headache diagnostics. It can be filled in during a consultation in order to
      provide the headache diagnosis or it can be printed and used by the headache
      patient to record headache attacks and medicine consumption. The nomenclature
      module provides an explanation of words and expressions used in the system.

PMID- 10886324
TI  - Diagnostic instruments for Creutzfeldt-Jacob's disease.

PMID- 10886325
TI  - Gabapentin in acute painful diabetic neuropathy.

PMID- 10886326
TI  - Arm trajectory and representation of movement processing in motor cortical
      activity.
AB  - We review experiments in which single-cell primary motor cortical activity was
      recorded from Rhesus monkeys (Macaca mulatta) while they performed reaching and
      drawing tasks. The directional tuning curves generated during reaching were
      modulated by the speed of movement and this was reflected in the magnitude of
      population vectors calculated from firing rates of a large population of cells.
      Directional and speed representation in the firing rates of these cells is robust
      across both reaching and drawing. Several behavioural invariants related to the
      speed of drawing were represented in the time-series of population vectors. This
      high fidelity neural representation of velocity found in motor cortex can be used
      to visualize the dynamics of motor cortical activity during drawing and suggests
      that the cost function governing the rate of drawing is bound by neural
      processing.

PMID- 10886327
TI  - Cloning and characterization of SDF-1gamma, a novel SDF-1 chemokine transcript
      with developmentally regulated expression in the nervous system.
AB  - The cytokines SDF-1alpha and -1beta are two alternatively spliced variants of the
      CXC (alpha) chemokines that are highly conserved among species. SDF-1alpha was
      shown to function as a B-cell maturation factor, a ligand for the CXCR4
      (LESTR/fusin) chemokine receptor, thereby inhibiting replication of T cell-tropic
      HIV-1 strains and inducing cell death in human neuronal cell lines. In this
      report the cloning of the rat SDF-1beta cDNA and a new SDF-1 isoform, SDF-1gamma,
      are presented. Using Northern blot analysis, the expression pattern of both
      isoforms was studied in different tissues and it is shown that during postnatal
      development of the central and peripheral nervous system SDF-1beta- and SDF
      1gamma-mRNA expression is inversely regulated. Whilst SDF-1beta-mRNA is the
      predominant isoform in embryonic and early postnatal nerve tissue, SDF-1gamma
      mRNA is expressed at higher levels in adulthood. After peripheral nerve lesion a
      transient increase in SDF-1beta-mRNA expression is observed. As revealed by in
      situ hybridization, neurons and Schwann cells are the main cellular sources of
      both SDF-1beta and SDF-1gamma mRNAs in the nervous system. Computer-assisted
      analysis revealed that both transcripts encode secreted peptides with putative
      proteolytic cleavage sites which might generate novel neuropeptides.

PMID- 10886328
TI  - SEK1/MKK4, c-Jun and NFKappaB are differentially activated in forebrain neurons
      during postnatal development and injury in both control and p75NGFR-deficient
      mice.
AB  - The common neurotrophin receptor (p75NGFR) can signal in vitro through activation
      of the c-Jun N-terminal kinase (JNK) pathway and nuclear translocation of
      NFKappaB. Activation of JNK and its substrate c-Jun can lead to apoptosis. We
      investigated these activities in vivo by comparing immunoreactivity for
      phosphorylated(p) SEK-1 (or MKK4, which activates JNK), c-Jun (ser63, ser73) and
      nuclear translocation of NFKappaB-p50 in tissue sections through the forebrain of
      control and p75NGFR-deficient mice. During postnatal development, SEK1p
      immunoreactivity was detectable in p75NGFR-positive cholinergic neurons and
      p75NGFR-negative neurons throughout the forebrain in control mice. During
      development, few cells contained c-Junp, although many neurons contained c-Jun.
      No obvious c-Jun immunostaining was present in the adult forebrain. At any age,
      NFKappaB-p50 immunoreactivity was seen in nuclei of most cells throughout the
      forebrain. Following fimbria fornix transection in adult mice, few basal
      forebrain neurons contained SEK1p while many axotomized choline acetyltransferase
      (ChAT)-positive neurons contained c-Junp and nuclear NFKappaB-p50. The
      immunostaining patterns of SEK1p, c-Junp and NFKB during development and
      following injury were largely similar in p75NGFR-deficient mice. During
      development, cells throughout the forebrain had TdT-mediated dUTP-biotin nick end
      labelling (TUNEL)-labelling (a potential marker for apoptosis), however, their
      presence was not predicted by number of neurons stained for SEK1p or c-Junp.
      These results suggest that the expected activation of the JNK pathway by p75NGFR,
      as well as the expected relationship between SEK1 and downstream activation of c
      Jun do not occur in the mammalian forebrain. Also, these results suggest that
      this activation does not necessarily lead to cell death.

PMID- 10886329
TI  - The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell
      death induced by beta-amyloid.
AB  - Substantial evidence suggests that the accumulation of beta-amyloid (Abeta)
      derived peptides, and to a lesser extent free radicals, may contribute to the
      aetiology and/or progression of Alzheimer's disease (AD). Ginkgo biloba extract
      (EGb 761) is a well-defined plant extract containing two major groups of
      constituents, i.e. flavonoids and terpenoids. It is viewed as a polyvalent agent
      with a possible therapeutic use in the treatment of neurodegenerative diseases of
      multifactorial origin, e.g. AD. We have investigated here the potential
      effectiveness of EGb 761 against toxicity induced by (Abeta)-derived peptides
      (Abeta25-35, Abeta1-40 and Abeta1-42) on hippocampal primary cultured cells, this
      area being severely affected in AD. A co-treatment with EGb 761 concentration
      dependently (10-100 microg/mL) protected hippocampal neurons against toxicity
      induced by Abeta fragments, with a maximal and complete protection at the highest
      concentration tested. Similar, albeit less potent protective effects were seen
      with the flavonoid fraction of the extract (CP 205), while the terpenes were
      ineffective. Most interestingly, EGb 761 (100 microg/mL) was even able to protect
      (up to 8 h) hippocampal cells from a pre-exposure to Abeta25-35 and Abeta1-40.
      EGb 761 was also able to both protect and rescue hippocampal cells from toxicity
      induced by H2O2 (50-150 microM), a major peroxide possibly involved in mediating
      Abeta toxicity. Moreover, EGb 761 (10-100 microg/mL), and to a lesser extent CP
      205 (10-50 microg/mL), completely blocked Abeta-induced events, e.g. reactive
      oxygen species accumulation and apoptosis. These results suggest that the
      neuroprotective effects of EGb 761 are partly associated with its antioxidant
      properties and highlight its possible effectiveness in neurodegenerative
      diseases, e.g. AD via the inhibition of Abeta-induced toxicity and cell death.

PMID- 10886330
TI  - Reciprocal actions of interleukin-6 and brain-derived neurotrophic factor on rat
      and mouse primary sensory neurons.
AB  - In low-density, serum-free cultures of neurons from embryonic rat dorsal root
      ganglia, interleukin-6 supports the survival of less than one third of the
      neurons yet virtually all of them bear interleukin-6 alpha-receptors. A finding
      that might explain this selectivity is that interleukin-6 acts on sensory neurons
      in culture through a mechanism requiring endogenous brain-derived neurotrophic
      factor. Antibodies or a trkB fusion protein that block the biological activity of
      brain-derived neurotrophic factor synthesized by dorsal root ganglion neurons
      also block the survival-promoting actions of interleukin-6 on these neurons. Two
      results indicate that interleukin-6 influences synthesis of brain-derived
      neurotrophic factor in adult dorsal root ganglion neurons. Intrathecal infusion
      of interleukin-6 in rats increases the concentration of brain-derived
      neurotrophic factor mRNA in rat lumbar dorsal root ganglia. The induction of
      brain-derived neurotrophic factor in dorsal root ganglion neurons that is seen
      after nerve injury in rats or wild-type mice is severely attenuated in mice with
      null mutation of the interleukin-6 gene. In brief, the ability of interleukin-6
      to support the survival of embryonic sensory neurons in vitro depends upon the
      presence of endogenous brain-derived neurotrophic factor and the induction of
      brain-derived neurotrophic factor in injured adult sensory neurons depends upon
      the presence of endogenous interleukin-6.

PMID- 10886331
TI  - Brain inflammatory reaction in an animal model of neuronal degeneration and its
      modulation by an anti-inflammatory drug: implication in Alzheimer's disease.
AB  - Brain inflammatory processes underlie the pathogenesis of Alzheimer's disease,
      and nonsteroidal anti-inflammatory drugs have a protective effect in the disease.
      The aim of this study was to characterize in vivo in the rat brain the
      inflammatory reaction in response to excitotoxic insult and to investigate the
      efficacy of nimesulide treatment. Quisqualic acid was injected into the right
      nucleus basalis of rats. The excitotoxin induced cholinergic degeneration, an
      intense glial reaction and the production of inflammatory mediators. Three hours
      after injection, a five-fold elevation in the concentration of interleukin-1beta
      in the injected area was observed. This elevation was reduced by 50% by
      nimesulide (10 mg/kg, i.m.) pretreatment. Electron microscope examination and
      immunocytochemical staining revealed an intense activation of microglia and
      astrocytes at both 24 h and 7 days after injection. Cyclooxygenase-2
      immunoreactivity was induced in the blood vessels of the injected hemisphere in
      perivascular microglial and endothelial cells 24 h after injection. Seven days
      postinjection, a cyclooxygenase-2-positive signal was induced in the parenchymal
      microglia and large amounts of prostaglandin-E2 were measured in the injected
      area. Twenty-four hours and 7 days after injection, many inducible nitric oxide
      synthase-positive cells and a high level of nitrite were detected at the
      injection site. Seven days of nimesulide (10 mg/kg/day, i.m.) treatment strongly
      attenuated the microglial reaction, reduced the number of inducible nitric oxide
      synthase-positive cells and completely abolished the increase in prostaglandin-E2
      formation. These data provide valuable support in vivo for the potential efficacy
      of cyclooxygenase-2 inhibitors in Alzheimer's disease therapy.

PMID- 10886332
TI  - Syntaxin 13 is a developmentally regulated SNARE involved in neurite outgrowth
      and endosomal trafficking.
AB  - In addition to its role in exocytosis, SNAP-25 is essential for axonal outgrowth.
      In order to identify SNARE proteins involved in neurite growth we have used SNAP
      25 antibodies to affinity-purify protein complexes enriched in developing rat
      brain membrane extracts. We have identified a complex between SNAP-25 and
      syntaxin 13 predominantly present in brain at embryonic or early postnatal
      stages. We show that syntaxin 13 is developmentally regulated with a decrease in
      adult brain. In differentiated neuroendocrine PC12 cells as well as primary
      cortical neurons the protein is localized to a punctated and tubular staining in
      the perinuclear region and along processes with high levels in the central region
      of growth cones. Carboxy-terminally tagged syntaxin 13 was also detected on the
      plasma membrane by in vivo surface-labelling where it colocalized with SNAP-25.
      Syntaxin 13 has recently been shown to be implicated in early endosomal
      trafficking. In our study, colocalization with internalized transferrin in the
      cell body and along neurites confirmed endosomal location in both compartments.
      Finally, overexpression of full-length syntaxin 13 enhanced neurite outgrowth in
      NGF-stimulated PC12 cells, whilst it had no effect on regulated secretion. The
      data suggest that a syntaxin 13-dependent endocytic trafficking step plays a
      limiting role in membrane expansion during neuronal development.

PMID- 10886333
TI  - Glycine triggers an intracellular calcium influx in oligodendrocyte progenitor
      cells which is mediated by the activation of both the ionotropic glycine receptor
      and Na+-dependent transporters.
AB  - Using fluo-3 calcium imaging, we demonstrate that glycine induces an increase in
      intracellular calcium concentration ([Ca2+]i) in cortical oligodendrocyte
      progenitor (OP) cells. This effect results from a calcium entry through voltage
      gated calcium channels (VGCC), as it is observed only in OP cells expressing such
      channels, and it is abolished either by removal of calcium from the extracellular
      medium or by application of an L-type VGCC blocker. Glycine-triggered Ca2+ influx
      in OP cells actually results from an initial depolarization that is the
      consequence of the activation of both the ionotropic glycine receptor (GlyR) and
      Na+-dependent transporters, most probably the glycine transporters 1 (GLYT1)
      and/or 2 (GLYT2) which are colocalized in these cells. Through this GlyR- and
      transporter-mediated effect on OP intrcellular calcium concentration [Ca2+]i,
      glycine released by neurons may, as well as other neurotransmitters, serve as a
      signal between neurons and OP during development.

PMID- 10886334
TI  - Polysorbate-80 coating enhances uptake of polybutylcyanoacrylate (PBCA)
      nanoparticles by human and bovine primary brain capillary endothelial cells.
AB  - Certain drugs such as dalargin, loperamide or tubocurarine are not transported
      across the blood-brain barrier (BBB) and therefore exhibit no effects on the
      central nervous system. However, effects on the central nervous system can be
      observed when these drugs are loaded onto polybutylcyanoacrylate (PBCA)
      nanoparticles and coated with polysorbate 80. The mechanism by which these
      complexed nanoparticles cross the BBB and exhibit their effects has not been
      elucidated. Cultured microvessel brain endothelial cells of human and bovine
      origin were used as an in vitro model for the BBB to gain further insight into
      the mechanism of uptake of nanoparticles. With cells from these species we were
      able to show that polysorbate 80-coated nanoparticles were taken up by brain
      endothelial cells much more rapidly and in significantly higher amounts (20-fold)
      than uncoated nanoparticles. The process of uptake was followed by fluorescence
      and confocal laser scanning microscopy. The results demonstrate that the
      nanoparticles are taken up by cells and that this uptake occurs via an
      endocytotic mechanism.

PMID- 10886335
TI  - Local GABAergic modulation of acetylcholine release from the cortex of freely
      moving rats.
AB  - Cortical perfusion with GABA agonists and antagonists modulates the spontaneous
      release of cortical acetylcholine and GABA in freely moving rats. Twenty-four
      hours after implantation of a dialysis fibre, cerebral cortex spontaneously
      released acetylcholine (3.8 +/- 0.2 pmol/10 min) and GABA (6.6 +/- 0.4 pmol/10
      min) at a stable rate. Local administration of GABA (1 or 5 mM) or the GABAA
      agonist muscimol (25 or 50 microM) had no effect on the spontaneous release of
      acetylcholine. However, bicuculline (1-25 microM), a GABAA antagonist, added to
      the dialysis perfusate, elicited a concentration-dependent increase of
      acetylcholine release to approximately double that of control. This effect of
      bicuculline (25 microM) was completely prevented by coperfusion with muscimol (50
      microM). Local administration of the GABAB receptor agonist baclofen (10 or 50
      microM) elicited a concentration-dependent increase in spontaneous acetylcholine
      release with a maximal increase of about 60%. Intracortical administration of
      baclofen also decreased the spontaneous release of GABA. The GABAB receptor
      antagonist CGP 35348 (1 mM), administered alone for 20 min through the dialysis
      fibre, was without effect on spontaneous acetylcholine release; however, it
      completely blocked both the baclofen-induced increase in acetylcholine release
      and the decrease in GABA release. These results suggest that cortically released
      GABA exerts a tonic influence on cholinergic activity.

PMID- 10886336
TI  - Suppression of the rat microglia Kv1.3 current by src-family tyrosine kinases and
      oxygen/glucose deprivation.
AB  - Microglia activate following numerous acute insults to the brain, including
      oxygen/glucose deprivation (OGD), and both protein tyrosine kinases (PTKs) and K+
      channels have been implicated in their activation. We identified Kv1.3 (voltage
      gated potassium channel) protein in cultured rat microglia and confirmed that the
      native current is biophysically and pharmacologically similar to Kv1. 3. To
      explore whether src-family PTKs regulate the microglial Kv current, we first
      heterologously expressed Kv1.3 in a microglia-like cell line derived from
      neonatal rat brain (MLS-9). The resulting large Kv1.3 current was eliminated by
      co-transfecting the constitutively active PTK, v-src, then rapidly restored by
      the PTK inhibitor, lavendustin A. Acute activation of endogenous src kinases by a
      peptide activator significantly reduced the current, an effect that was mimicked
      by OGD. Similarly, in primary cultures of rat microglia, the endogenous Kv1.3
      like current was inhibited by activating endogenous src-family PTKs and by OGD.
      Biochemical analysis showed that OGD increased the tyrosine phosphorylation of
      native Kv1.3 protein, which was alleviated by PTK inhibitors or reactive oxygen
      species (ROS) scavengers. Conversely, the basal level of Kv1.3 phosphorylation
      was decreased by PTK inhibitors or scavengers of ROS. Together, our results point
      to a post-insertional downregulation of the microglial Kv1.3-like current by
      oxidative stress and tyrosine phosphorylation. This interaction may be
      facilitated by a multiprotein complex because, in cultured microglia, the
      endogenous Kv1.3 and src proteins both bind to the scaffolding protein, post
      synaptic density protein 95 (PSD-95). By associating with, and phosphorylating
      Kv1.3, src is well positioned to regulate microglial responses to oxidative
      stress.

PMID- 10886337
TI  - A new class of neurotoxin from wasp venom slows inactivation of sodium current.
AB  - The effects of alpha-pompilidotoxin (alpha-PMTX), a new neurotoxin isolated from
      the venom of a solitary wasp, were studied on the neuromuscular synapses in
      lobster walking leg and the rat trigeminal ganglion (TG) neurons. Paired
      intracellular recordings from the presynaptic axon terminals and the innervating
      lobster leg muscles revealed that alpha-PMTX induced long bursts of action
      potentials in the presynaptic axon, which resulted in facilitated excitatory and
      inhibitory synaptic transmission. The action of alpha-PMTX was distinct from that
      of other known facilitatory presynaptic toxins, including sea anemone toxins and
      alpha-scorpion toxins, which modify the fast inactivation of Na+ current. We
      further characterized the action of alpha-PMTX on Na+ channels by whole-cell
      recordings from rat trigeminal neurons. We found that alpha-PMTX slowed the Na+
      channels inactivation process without changing the peak current-voltage
      relationship or the activation time course of tetrodotoxin (TTX)-sensitive Na+
      currents, and that alpha-PMTX had voltage-dependent effects on the rate of
      recovery from Na+ current inactivation and deactivating tail currents. The
      results suggest that alpha-PMTX slows or blocks conformational changes required
      for fast inactivation of the Na+ channels on the extracellular surface. The
      simple structure of alpha-PMTX, consisting of 13 amino acids, would be
      advantageous for understanding the functional architecture of Na+ channel
      protein.

PMID- 10886338
TI  - Organization of connections of the basal and accessory basal nuclei in the monkey
      amygdala.
AB  - The present study investigated the intrinsic connections of the basal and
      accessory basal nuclei of the Macaca fascicularis monkey by means of the
      anterograde tracers Phaseolus vulgaris-leucoagglutinin (PHA-L) and biotinylated
      dextran amine (BDA). Analysis of the intranuclear connections of the basal
      nucleus indicates that there are five modules: dorsal, intermediate, ventral
      lateral, ventral medial and periamygdaloid sulcal cortex. The dorsal division
      projects to the intermediate division. Laterally, the intermediate division
      projects to the ventral lateral division and dorsal parts of the ventral medial
      division. Ventrally, the ventral lateral division projects to the ventral medial
      division and periamygdaloid sulcal cortex, which appears to constitute a medial
      extension of the basal nucleus onto the cortical surface of the amygdala.
      Medially, the ventral medial division projects to the intermediate and dorsal
      divisions. Thus, the connections between these modules form functional
      microcolumns within the nucleus with distinct patterns of information flow that
      are dorsal to ventral laterally, lateral to medial ventrally, and ventral to
      dorsal medially. Observations on the intranuclear connections of the accessory
      basal nucleus suggest that they are organized into two relatively distinct
      domains: the dorsal division projects to the ventral division and the ventral
      division projects primarily to the ventromedial division. Projections to other
      amygdaloid areas originate in select divisions of the basal and accessory basal
      nuclei, and are topographically distributed. The organization of intrinsic
      connections of the basal nuclei correlates with specific amygdalo-cortical
      connections and suggests that extensive convergence of information takes place
      within the amygdala, which potentially influences activity at both the temporal
      and parietal pathways and hippocampal fields.

PMID- 10886339
TI  - Protein kinase C activity modulates dendritic differentiation of rat Purkinje
      cells in cerebellar slice cultures.
AB  - The molecular mechanisms underlying dendritic differentiation in neurons are
      currently poorly understood. We used slice cultures from rat cerebellum of
      postnatal day 8 to investigate the effect of protein kinase C (PKC) activity on
      dendritic development of Purkinje cells. After 12 days in culture under control
      conditions, Purkinje cells had developed a typical dendritic tree consisting of a
      few long primary dendrites with shorter side branches. Following treatment with
      the PKC agonist, phorbol-12-myristate-13-acetate (PMA), the dendritic tree area
      was strongly reduced to 32% of control and primary dendrites were short with only
      a few side branches. Delayed addition of PMA after 6 days resulted in a
      retraction of existing dendrites, whereas discontinuation of PMA treatment after
      6 days resulted in a recovery of the dendritic tree to almost control values. In
      the presence of the PKC inhibitor, 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3
      (indol-3-yl)maleimide (GF109203X), the dendritic tree area was increased to 158%
      of control with much more ramified branches after 12 days. The overall morphology
      of the cultures and the survival of Purkinje cells were unaffected by PKC
      modulators. Our data show that increased activity of PKC inhibits, and reduced
      activity of PKC promotes dendritic growth. This suggests that PKC activity is a
      critical regulator of dendritic growth and differentiation in cerebellar Purkinje
      cells.

PMID- 10886340
TI  - Cellular mechanisms of hyperalgesia and spontaneous pain in a spinalized rat
      model of peripheral neuropathy: changes in myelinated afferent inputs implicated.
AB  - Various hypotheses have been proposed to account for the mechanical hyperalgesia
      and spontaneous pain seen in animal models of peripheral neuropathy. The purpose
      of the present study was to determine whether there exists a spinal neuronal
      correlate to these properties. An experimental neuropathy was induced in male
      Sprague-Dawley rats by placing a 2-mm PE-90 polyethylene cuff around the sciatic
      nerve. All rats were subsequently confirmed to exhibit mechanical allodynia in
      the von Frey test. After induction of anaesthesia with pentobarbital and acute
      spinalization at T9, electrophysiological experiments were performed, recording
      extracellular single unit activity from ipsi- and contralateral wide dynamic
      range dorsal horn neurons in spinal segments L1-4. On-going activity was greater
      in short-term (11-22 days after cuff implantation) and long-term (42-52 days)
      cuff-implanted rats; 38 spikes/s in short-term versus 19 spikes/s in controls; 29
      spikes/s in long-term ipsi- and contralateral neurons. Receptive fields in
      controls were always restricted, but in almost all cuff-implanted rats extended
      over the whole hind paw. Responses to noxious mechanical (pinch) and noxious heat
      stimulation of the cutaneous receptive field in controls consisted of the typical
      fast initial discharge followed by an afterdischarge. In all neurons from cuff
      implanted rats the initial discharge resembled that in controls. However, the
      afterdischarge, particularly that in response to noxious pinch, was markedly
      greater in both magnitude and duration. It is suggested that the greater on-going
      discharge is the cellular correlate of spontaneous pain, and the potentiation of
      the afterdischarge in response to noxious stimulation is the correlate of
      hyperalgesia. Given that acutely spinalized rats were tested, only peripheral
      and/or spinal mechanisms can be considered to explain these data. Considering all
      the data, it can be concluded that there is a greater change in fibres mediating
      noxious mechanical than noxious thermal inputs. Among different hypotheses, the
      one with which the present data are most compatible is that which proposes that
      chronic nerve injury or inflammation induces phenotypic changes predominantly in
      myelinated afferents. There may be a redistribution of membrane-bound ion
      channels, predominantly sodium channels, which leads to ectopic activity and thus
      spontaneous discharge of dorsal horn neurons. With regard to mechanical
      stimulation-evoked synaptic input, the central terminals of myelinated afferents
      expand into regions of the spinal cord which normally receive their predominant
      input from unmyelinated nociceptive afferents. This may be coupled with a change
      in these myelinated afferents so that they now synthesize and release peptides,
      primarily substance P, from their central terminals with the result that the
      effects of their chemical mediators of synaptic transmission add to the effects
      of nociceptive inputs leading to exaggerated responses to painful stimuli, thus
      the basis of clinical hyperalgesia.

PMID- 10886341
TI  - Role of desensitization of AMPA receptors on the neuronal viability and on the
      [Ca2+]i changes in cultured rat hippocampal neurons.
AB  - We investigated the role of desensitization of alpha-amino-3-hydroxy-5-methyl
      isoxazole-4-propionate (AMPA) receptors on the neurotoxicity and on the [Ca2+]i
      changes induced by kainate or by AMPA in cultured rat hippocampal neurons. The
      neuronal viability was evaluated either by the 3-(4,5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT) assay, or by analysis of cell morphology. Short
      term exposure of the neurons to kainate or AMPA (30 min) was not toxic, but the
      exposure for 24 h to the excitotoxic drugs caused a concentration-dependent
      neurotoxic effect which was prevented by LY 303070, a noncompetitive AMPA
      receptor antagonist. In the presence of cyclothiazide (CTZ), kainate or AMPA was
      toxic (30 min exposure), or the toxic effect was significantly enhanced (24 h
      exposure), but in this case LY 303070 did not completely protect the cells
      against kainate-induced toxicity. The alterations in the [Ca2+]i caused by
      kainate or AMPA showed a great cell-to-cell variability. LY 303070 completely or
      partially inhibited the responses stimulated by kainate. CTZ differentially
      affected the responses evoked by kainate or AMPA. In the majority of hippocampal
      neurons, CTZ did not potentiate, or only slightly potentiated, the kainate
      stimulated responses but in 11% of neurons there was a great potentiation. In
      AMPA-stimulated neurons, the responses were slightly or greatly potentiated in
      the majority of neurons, but not in all of them. The results show that AMPA and
      kainate may be toxic, depending on the time of exposure and on the blockade of
      the desensitization of the AMPA receptors. Overall, our results clearly show that
      there exist different populations of hippocampal neurons with different
      sensitivities to kainate, AMPA, CTZ and LY 303070. Moreover, the effects of CTZ
      on both [Ca2+]i alterations and neurotoxicity are not fully correlated.

PMID- 10886342
TI  - Glial cell line-derived neurotrophic factor modulates ischemia-induced tyrosine
      hydroxylase expression in rat hippocampus.
AB  - Recently, we have reported that glial cell line-derived neurotrophic factor
      (GDNF), which supports the survival of dopaminergic neurons, prevents delayed
      neuronal death in the hippocampal CA1 region induced by transient forebrain
      ischemia. In the present study, we examined the role of GDNF in the expression of
      tyrosine hydroxylase (TH) mRNA induced by transient forebrain ischemia in rats.
      The expression of TH mRNA was increased in a time-dependent manner, with a
      significant increase in 24 h to 7 days, in the hippocampus after induction of
      transient forebrain ischemia, as determined using the reverse transcription and
      polymerase chain reaction method. Although it has been suggested that the
      increase of dopamine beta-hydroxylase mRNA expression correlates with the
      activation of noradrenergic neurons, no increase of dopamine beta-hydroxylase
      mRNA in the hippocampus was observed in our system. Western blot analysis
      revealed that TH protein, but not dopamine beta-hydroxylase protein, was produced
      in a time-dependent manner in the hippocampus during the ischemia. Interestingly,
      the induction level of TH mRNA was reduced by intrahippocampal microinjection of
      GDNF (1.0 microg), and this local GDNF treatment also reduced the increase of TH
      like immunohistochemistry-positive terminals in the hippocampus. In contrast,
      local GDNF treatment of normal rats increased the TH mRNA expression at 6-12 h.
      These findings suggest that GDNF protects against neuronal degeneration including
      delayed neuronal death in the hippocampal CA1 region by modulating the expression
      levels of TH mRNA and protein.

PMID- 10886343
TI  - Effects of barium on stimulus-induced rises of [K+]o in human epileptic non
      sclerotic and sclerotic hippocampal area CA1.
AB  - In the hippocampus of patients with therapy-refractory temporal lobe epilepsy,
      glial cells of area CA1 might be less able to take up potassium ions via barium
      sensitive inwardly rectifying and voltage-independent potassium channels. Using
      ion-selective microelectrodes we investigated the effects of barium on rises in
      [K+]o induced by repetitive alvear stimulation in slices from surgically removed
      hippocampi with and without Ammon's horn sclerosis (AHS and non-AHS). In non-AHS
      tissue, barium augmented rises in [K+]o by 147% and prolonged the half time of
      recovery by 90%. The barium effect was reversible, concentration dependent, and
      persisted in the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
      (AMPA), N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid [GABA(A)]
      receptor antagonists. In AHS tissue, barium caused a decrease in the baseline
      level of [K+]o. In contrast to non-AHS slices, in AHS slices with intact synaptic
      transmission, barium had no effect on the stimulus-induced rises of [K+]o, and
      the half time of recovery from the rise was less prolonged (by 57%). Under
      conditions of blocked synaptic transmission, barium augmented stimulus-induced
      rises in [K+]o, but only by 40%. In both tissues, barium significantly reduced
      negative slow-field potentials following repetitive stimulation but did not alter
      the mean population spike amplitude. The findings suggest a significant
      contribution of glial barium-sensitive K+-channels to K+-buffering in non-AHS
      tissue and an impairment of glial barium-sensitive K+-uptake in AHS tissue.

PMID- 10886344
TI  - Electrophysiological properties of microglial cells in normal and pathologic rat
      brain slices.
AB  - Microglial cells serve as pathologic sensors of the brain. They are highly
      abundant in all regions of the central nervous system (CNS) and are characterized
      by a ramified morphology within the normal tissue. In the present study, we have
      developed a procedure to study the membrane properties of identified, in situ
      microglia in acutely isolated brain slices from rat cortex, striatum and facial
      nucleus. Unlike the well characterized cultured microglial cells, ramified
      microglia of the slice are characterized by little, if any, voltage-gated
      membrane currents and a very low membrane potential. They are thus distinct from
      neurons, other glial cells and nonbrain macrophages. To study the consequences of
      microglial activation on the membrane channel pattern, we compared cells in the
      normal facial nucleus and at defined times after facial nerve axotomy. Within 12
      h of axotomy, microglial cells expressed a prominent inward rectifier current and
      thus acquired the physiological properties of cultured microglia. Within 24 h of
      the lesion, the cells expressed an additional outward current, which is typical
      for lipopolysaccharide (LPS)-activated microglia in vitro. Seven days after the
      lesion, at a time of major regenerative processes in the facial nucleus, the
      physiological properties of microglial cells had reverted to those present prior
      to the pathological event. IN CONCLUSION: (i) ramified microglial cells represent
      a physiologically unique population of cells in the brain; (ii) are distinct from
      their cultured counterparts; and (iii), undergo a defined pattern of
      physiological states in the course of pathologic events.

PMID- 10886345
TI  - IAP family proteins delay motoneuron cell death in vivo.
AB  - Neuronal apoptosis inhibitory protein (NAIP), and human inhibitors of apoptosis 1
      and 2 (HIAP1 and HIAP2) are three members of the mammalian family of
      antiapoptosis proteins called 'inhibitors of apoptosis' (IAP). These molecules
      can prevent apoptosis in vitro and the over-expression of NAIP can decrease
      ischemic damage in the hippocampus. The goal of our experiments was to determine
      whether administration of NAIP, HIAP1 and HAIP2 could rescue motoneurons
      following axotomy of a peripheral nerve. In young rats, an adenoviral gene
      transfer technique was used to deliver and express these proteins in motoneurons;
      a fluorescent tracer was simultaneously added as a means for quantitatively
      assessing the rescue of fluorescently labelled motoneurons in serial sections of
      the lumbar spinal cord. Control experiments using adenoviral vectors (adv)
      expressing the lacZ gene showed that 14% of the sciatic motoneuron pool could be
      transfected indicating the existence of a subpopulation of spinal motoneurons
      susceptible to this class of viral vectors. The administration of an adv-NAIP,
      adv-HIAP1 and adv-HIAP2 rescued 30-40% of motoneurons at one week after sciatic
      axotomy. The efficiency of these proteins was similar to that of two neurotrophic
      factors, ciliary neurotrophic factor and brain-derived neurotrophic factor,
      administrated by the same viral technique. The effect of the IAP proteins on
      motoneuron survival decreased with time but was still present after 4 weeks
      postaxotomy; the duration of the response was dependent upon the viral titre.
      These experiments demonstrate that IAP family proteins can prevent motoneuron
      cell death in vivo and may offer a new therapeutic approach for motoneuron
      diseases.

PMID- 10886346
TI  - Q- and L-type calcium channels control the development of calbindin phenotype in
      hippocampal pyramidal neurons in vitro.
AB  - Cultured immature hippocampal neurons from embryonic 17-day-old rats were used to
      explore activity-dependent regulation of neuronal phenotype differentiation in
      the developing hippocampus. The calbindin-D28k phenotype of the pyramidal neurons
      appeared during the first 6 days in culture, and was expressed by 12% of the
      cells on day 6. Daily stimulation with 50 mM KCl during the first 5 days in vitro
      increased the number of calbindin-D28k-positive pyramidal neurons without
      affecting neuronal survival. This effect was prevented by buffering extracellular
      Ca2+. Omega-agatoxin-IVA-sensitive Q-type and nitrendipine-sensitive L-type
      voltage-gated Ca2+ channels (VGCCs) carried Ca2+ currents and Ca2+ influx in
      immature pyramidal neurons at somata level. Blockade of these channels inhibited
      calbindin-D28k phenotype induced by 50 mM KCl. Conversely, glutamate-activated
      Ca2+ channel antagonists did not affect the KCl-induced calbindin-D28k phenotype.
      Chronic blockade of Q- and/or L-type VGCCs downregulated the normal calbindin
      D28k development of immature pyramidal neurons without affecting neuronal
      survival, the somatic area of pyramidal neurons or the number of GABAergic
      positive (gamma-aminobutyric acid) interneurons. However, at later developmental
      stages, Q-type VGCCs lost their ability to control Ca2+ influx at somata level,
      and both Q- and L-type VGCCs failed to regulate calbindin-D28k phenotype. These
      results suggest that Q-type channels, which have been predominantly associated
      with neurotransmitter release in adult brain, transiently act in synergy with L
      type VGCCs to direct early neuronal differentiation of hippocampal pyramidal
      neurons before the establishment of their synaptic circuits.

PMID- 10886347
TI  - Activation of spinal cannabinoid 1 receptors inhibits C-fibre driven
      hyperexcitable neuronal responses and increases [35S]GTPgammaS binding in the
      dorsal horn of the spinal cord of noninflamed and inflamed rats.
AB  - The analgesic potential of cannabinoid (CB) receptor agonists is of clinical
      interest. Improved understanding of the mechanisms of action of cannabinoids at
      sites involved in the modulation of acute and sustained inflammatory nociceptive
      transmission, such as the spinal cord, is essential. In vivo electrophysiology
      was used to compare the effect of the synthetic CB agonist, HU210, on acute
      transcutaneous electrical-evoked responses of dorsal horn neurons of noninflamed
      anaesthetized rats and anaesthetized rats with a peripheral carrageenin
      inflammation. CB receptor G-protein coupling in lumbar spinal cord sections of
      noninflamed and carrageenin-inflamed rats was studied with in vitro
      autoradiography of guanylyl 5'-[gamma-[35S]thio]triphosphate ([35S]GTPgammaS)
      binding. Spinal HU210 significantly inhibited the C-fibre-mediated late (300-800
      ms) postdischarge response of dorsal horn neurons of noninflamed and carrageenin
      inflamed rats; the CB1 receptor antagonist SR141716A blocked the effect of HU210.
      HU210 had limited effects on A-fibre-evoked dorsal horn neuronal responses of
      both groups of rats. HU210 significantly increased [35S]GTPgammaS binding in the
      dorsal horn of the spinal cord of both groups of rats compared with basal
      [35S]GTPgammaS binding; SR141716A blocked these effects. The predominant effect
      of spinal HU210, via CB1 receptor activation, was on the C-fibre driven
      postdischarge responses, a measure of neuronal hyperexcitability following
      repetitive C-fibre stimulation. Sustained, but not enhanced, antinociceptive
      effects of HU210 following carrageenin inflammation are reported; CB receptor G
      protein coupling was not altered by inflammation. These results strengthen the
      body of evidence suggesting CB agonists may be an important novel analgesic
      approach for the treatment of sustained pain states.

PMID- 10886348
TI  - Astrocytes in the hippocampus of patients with temporal lobe epilepsy display
      changes in potassium conductances.
AB  - Functional properties of astrocytes were investigated with the patch-clamp
      technique in acute hippocampal brain slices obtained from surgical specimens of
      patients suffering from pharmaco-resistant temporal lobe epilepsy (TLE). In
      patients with significant neuronal cell loss, i.e. Ammon's horn sclerosis, the
      glial current patterns resembled properties characteristic of immature astrocytes
      in the murine or rat hippocampus. Depolarizing voltage steps activated delayed
      rectifier and transient K+ currents as well as tetrodotoxin-sensitive Na+
      currents in all astrocytes analysed in the sclerotic human tissue.
      Hyperpolarizing voltages elicited inward rectifier currents that inactivated at
      membrane potentials negative to -130 mV. Comparative recordings were performed in
      astrocytes from patients with lesion-associated TLE that lacked significant
      histopathological hippocampal alterations. These cells displayed stronger inward
      rectification. To obtain a quantitative measure, current densities were
      calculated and the ratio of inward to outward K+ conductances was determined.
      Both values were significantly smaller in astrocytes from the sclerotic group
      compared with lesion-associated TLE. During normal development of rodent brain,
      astroglial inward rectification gradually increases. It thus appears reasonable
      to suggest that astrocytes in human sclerotic tissue return to an immature
      current pattern. Reduced astroglial inward rectification in conjunction with
      seizure-induced shrinkage of the extracellular space may lead to impaired spatial
      K+ buffering. This will result in stronger and prolonged depolarization of glial
      cells and neurons in response to activity-dependent K+ release, and may thus
      contribute to seizure generation in this particular condition of human TLE.

PMID- 10886349
TI  - Expression of Fos-related antigens in the nucleus accumbens and associated
      regions following exposure to a cocaine-paired environment.
AB  - This study examined whether conditioned hyperactivity measured in a cocaine
      paired environment was associated with increased expression of Fos-related
      antigens (FRA) within the nucleus accumbens (NAc) and associated forebrain
      regions of rats. Three groups of rats were given repeated injections of either
      cocaine in the test environment and saline in the colony room (group Paired),
      saline in the test environment and cocaine in the colony room (group Unpaired),
      or saline in both environments (group Control). All rats were subsequently given
      a drug-free test for conditioned hyperactivity in the test environment, and their
      brains were removed so that FRA immunohistochemistry could be conducted. Rats in
      the Paired group showed conditioned hyperactivity during the conditioning test,
      and this behavioural response was associated with increased FRA expression within
      the caudal NAc, the medial prefrontal cortex and the lateral septum relative to
      the Unpaired and Control groups. Paired rats also showed increased FRA expression
      within the orbital prefrontal cortex, the claustrum, the caudal amygdala
      (basolateral and central regions), the paraventricular thalamic nucleus, the
      subiculum of the hippocampus, and the lateral habenula relative to the Control
      group. However, the FRA levels in these latter sites were not significantly
      increased relative to those of Unpaired rats, indicating that genomic responses
      in these regions were not entirely context dependent. The correspondence between
      conditioned hyperactivity and enhanced FRA expression within the caudal NAc, the
      medial prefrontal cortex and lateral septum suggests that these regions may
      participate in the expression of conditioned responses to cocaine-related
      stimuli.

PMID- 10886350
TI  - Basal forebrain neurons suppress amygdala kindling via cortical but not
      hippocampal cholinergic projections in rats.
AB  - Intraventricular administration of the immunotoxin 192 IgG-saporin in rats has
      been shown to cause a selective loss of cholinergic afferents to the hippocampus
      and cortical areas, and to facilitate seizure development in hippocampal
      kindling. Here we demonstrate that this lesion also accelerates seizure
      progression when kindling is induced by electrical stimulations in the amygdala.
      However, whereas intraventricular 192 IgG-saporin facilitated the development of
      the initial stages of hippocampal kindling, the same lesion promoted the late
      stages of amygdala kindling. To explore the role of various parts of the basal
      forebrain cholinergic system in amygdala kindling, selective lesions of the
      cholinergic projections to either hippocampus or cortex were produced by
      intraparenchymal injections of 192 IgG-saporin into medial septum/vertical limb
      of the diagonal band or nucleus basalis, respectively. Cholinergic denervation of
      the cortical regions caused acceleration of amygdala kindling closely resembling
      that observed after the more widespread lesion induced by intraventricular 192
      IgG-saporin. In contrast, removal of the cholinergic input to the hippocampus had
      no effect on the development of amygdala kindling. These data indicate that basal
      forebrain cholinergic neurons suppress kindling elicited from amygdala, and that
      this dampening effect is mediated via cortical but not hippocampal projections.

PMID- 10886352
TI  - Spatio-temporal characterizations of non-linear changes in intracranial
      activities prior to human temporal lobe seizures.
AB  - Recent studies have shown that non-linear analysis of intracranial activities can
      detect a 'pre-ictal phase' preceding the epileptic seizure. Nevertheless, the
      dynamical nature of the underlying neuronal process and the spatial extension of
      this pre-ictal phase still remain unknown. In this paper, we address these
      aspects using a new non-linear measure of dynamic similarity between different
      parts of intracranial recordings of nine patients with medial temporal lobe
      epilepsy recorded during transitions to seizure. Our results confirm that non
      linear changes in neuronal dynamics allow, in most cases (16 out of 17), a
      seizure anticipation several minutes in advance. Furthermore, we show that the
      spatial distribution of pre-ictal changes often involves an extended network
      projecting beyond the limits of the epileptogenic region. Finally, the pre-ictal
      phase could frequently (13 out of 17) be characterized with a marked shift toward
      slower frequencies in upper delta or theta frequency range.

PMID- 10886351
TI  - Involvement of the direct striatonigral pathway in levodopa-induced sensitization
      in 6-hydroxydopamine-lesioned rats.
AB  - Induction of dopamine D3 receptor gene expression in 6-hydroxydopamine-lesioned
      rats by repeated administration of levodopa had been suggested to be responsible
      for behavioural sensitization developing in these animals. Using double in situ
      hybridization techniques, we show that D3 receptor mRNA induction after repeated
      administration of levodopa took place mainly in dynorphin/substance P-expressing
      neurons of the direct striatonigral pathway. In agreement, induction of D3
      receptor binding sites was evidenced, using 7-[3H]hydroxy-N,N-di-propyl-2
      aminotetralin ([3H]7-OH-DPAT), in substantia nigra pars reticulata, the
      projection area of the direct nigrostriatonigral pathway. Changes in D3 receptor
      binding and behavioural sensitization during intermittent administration of
      levodopa paralleled changes in prodynorphin/preprotachykinin rather than
      preproenkephalin/prodynorphin and preproenkephalin/preprotachykinin mRNA ratios.
      Behavioural sensitization, induction of D3 receptor binding and changes in
      prodynorphin/preprotachykinin ratio were all prevented together when levodopa was
      continuously delivered or intermittently delivered in combination with R-(+)-7
      chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine (SCH
      23390), a selective D1 receptor antagonist. Our results indicate that functional
      changes of the direct striatal output pathway, possibly through an interaction
      between D1 and D3 receptors at the level of terminals in the substantia nigra
      pars reticulata, are important for the development of behavioural sensitization.

PMID- 10886353
TI  - The activity-dependent plasticity of segmental and intersegmental synaptic
      connections in the lamprey spinal cord.
AB  - Activity-dependent synaptic plasticity has been proposed as a contributory factor
      in the patterning of rhythmic network activity. However, its role has not been
      examined in detail. Here, paired or triple intracellular recordings have been
      made from identified neurons in the lamprey locomotor network to examine the
      potential relevance of activity-dependent synaptic plasticity in segmental and
      intersegmental spinal networks. Segmental inputs from glutamatergic excitatory
      interneurons (EIN) to ipsilateral glycinergic crossed caudal (CC) interneurons
      were facilitated or depressed during spike trains at 5-20 Hz. Connections between
      EINs were depressed. Glycinergic inputs from small ipsilateral inhibitory
      interneurons were depressed in motor neurons, but were facilitated in CC
      interneurons. Excitatory inputs from small crossing interneurons to motor neurons
      were depressed, whereas inhibitory inputs were unaffected. With the exception of
      connections between EINs, significant effects occurred with stimulation that
      mimicked interneuron spiking during network activity. Intersegmental EIN synaptic
      properties were also investigated. EIN inputs did not differ significantly when
      examined from zero to four segments rostral to motor neurons or CC interneurons.
      However, caudally located EINs evoked greater activity-dependent facilitation
      than did rostral EINs. Whilst the amplitude or plasticity of EIN inputs in the
      rostral or mid-trunk regions of the spinal cord did not differ, EINs in the
      caudal trunk region evoked greater facilitation. Synaptic transmission between
      locomotor network neurons thus exhibits activity-dependent plasticity in response
      to physiologically relevant stimulation. Activity-dependent plasticity could thus
      contribute to the patterning of the rhythmic network output.

PMID- 10886354
TI  - Temporal integration vs. parallel processing: coping with the variability of
      neuronal messages in directional hearing of insects.
AB  - The behaviour of many animals indicates a high precision in the processing of
      sensory signals, which often seems at odds with the large variability of
      individual neuronal responses. Using the directional hearing of the grasshopper
      Chorthippus biguttulus (Ch. biguttulus) as a model system, we investigated the
      possible contributions of temporal integration and parallel processing at the
      receptor level to the observed behavioural acuity. The precision of the animals'
      phonotactic orientation behaviour to stimuli of different durations was measured
      and compared with the spiking responses of auditory receptor cells, leading to
      the following results. A behavioural decision based on integrating the spikes
      from a pair of receptors (one cell in each ear) over a 1000-ms time window would
      substantially decrease the error probability, compared with evaluating a 250-ms
      period. The animal as a whole, however, responded as precisely to a 250 ms
      stimulus as to a stimulus of natural duration (c. 1000 ms). A phonotactic
      decision based on a 1.5 dB intensity difference between the ears corresponds to a
      spike count difference of approximately 1 spike per 100 ms in a pair of
      receptors. As these differences are in the order of the statistical spike count
      fluctuations, the error probabilities for an ideal observer of the spike count
      are substantially higher (13-18%) than the errors observed in the behavioural
      tests (only 5%). We conclude that the animals' nervous system has to sample
      information from a pool of 6-13 receptors to arrive at the observed behavioural
      precision.

PMID- 10886355
TI  - Synaptic interactions increase optic flow specificity.
AB  - Representations of optic flow are encoded in fly tangential neurons by pooling
      the signals of many retinotopically organized local motion-sensitive inputs as
      well as of other tangential cells originating in the ipsi- and contralateral half
      of the brain. In the so called HSE cell, a neuron involved in optomotor course
      control, two contralateral input elements, the H1 and H2 cells, mediate distinct
      EPSPs. These EPSPs frequently elicit spike-like depolarizations in the HSE cell.
      The synaptic transmission between the H2 and the HSE cell is analysed in detail
      and shown to be very reliable with respect to the amplitude and time-course of
      the postsynaptic potential. As a consequence of its synaptic input, the HSE cell
      responds best to wide-field motion, such as that generated on the eyes when the
      animal turns about its vertical body axis. It is shown that the specificity of
      the HSE cell for this type of optic flow is much enhanced if rapid membrane
      depolarizations, such as large-amplitude EPSPs or spike-like depolarizations, are
      taken into account rather than the average membrane potential.

PMID- 10886356
TI  - Effects of glutamate agonist versus procaine microinjections into the basal
      forebrain cholinergic cell area upon gamma and theta EEG activity and sleep-wake
      state.
AB  - Serving as the ventral, extra-thalamic relay from the brainstem reticular
      activating system to the cerebral cortex, basal forebrain neurons, including
      importantly the cholinergic cells therein, are believed to play a significant
      role in eliciting and maintaining cortical activation during the states of waking
      and paradoxical sleep. The present study was undertaken in rats to examine the
      effects upon electroencephalogram (EEG) activity and sleep-wake state of
      inactivating basal forebrain neurons with microinjections of procaine versus
      activating them with microinjections of agonists of glutamate, which is the
      primary neurotransmitter of the brainstem reticular activating system.
      Microinjections into the basal forebrain were performed using a remotely
      controlled device in freely moving, naturally sleeping/waking rats during the day
      when they are asleep the majority of the time. Procaine produced a decrease in
      gamma (30-60 Hz) and theta (4-8 Hz) EEG activities, and an increase in delta (1-4
      Hz) associated with a loss of paradoxical sleep, despite the persistence of slow
      wave sleep. alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and
      N-methyl-D-aspartate (NMDA) produced an increase in gamma and a decrease in
      delta, while eliciting waking. In addition, NMDA, which has been shown in vitro
      to induce rhythmic bursting in the cholinergic cells, significantly increased
      theta activity. Following the microinjections of NMDA, c-Fos protein, which has
      been shown to reflect neural activity, was found in numerous cholinergic, and
      also GABAergic (gamma-aminobutyric acid) and other non-cholinergic neurons, in
      the substantia innominata and magnocellular preoptic nucleus near the
      microinjection cannulae. These results substantiate the role of cholinergic,
      possibly together with other, basal forebrain neurons in cortical activation,
      including elicitation of gamma and theta activities that underlie cortical
      arousal during waking and paradoxical sleep.

PMID- 10886357
TI  - Time-dependent enhancement of inhibitory avoidance retention and MAPK activation
      by post-training infusion of nerve growth factor into CA1 region of hippocampus
      of adult rats.
AB  - Several studies have demonstrated that chronic intracerebroventricular nerve
      growth factor (NGF) infusion has a beneficial effect on cognitive performance of
      lesioned as well as old and developing animals. Here we investigate: (i) the
      effect of post-training infusion of NGF into the CA1 region of hippocampus on
      inhibitory avoidance (IA) retention in rats; (ii) the extension of the effect, in
      time and space, of NGF infusion into CA1 on the activity of mitogen-activated
      protein kinase (MAPK, syn: ERK1/2, p42/p44 MAPK). NGF was bilaterally injected
      into the CA1 regions of the dorsal hippocampus (0.05, 0.5 or 5.0 ng diluted in
      0.5 microL of saline per side ) at 0, 120 or 360 min after IA training in rats.
      Retention testing was carried out 24 h after training. The injection of 5.0 and
      0.5, but not 0.05, ng per side of NGF at 0 and 120 min after IA training enhanced
      IA retention. The highest dose used was ineffective when injected 360 min after
      training. The infusion of 0. 5 microL of NGF (5.0 ng) induced a significant
      enhancement of MAPK activity in hippocampal microslices; this enhancement was
      restricted to a volume with 0.8 mm radius at 30 min after injection. The MAPK
      activation was still seen 180 min after NGF infusion, although this value showed
      only a tendency. In conclusion, localized infusion of NGF into the CA1 region
      enhanced MAPK activity, restricted in time and space, and enhanced IA retention
      in a time- and dose-dependent manner.

PMID- 10886358
TI  - Facial nerve injury-induced disinhibition in the primary motor cortices of both
      hemispheres.
AB  - Unilateral facial nerve transection induces plastic reorganization of the
      somatotopic order in the primary motor cortex area (MI). This process is biphasic
      and starts with a transient disinhibition of connections between cortical areas
      in both hemispheres. Little is known about the underlying mechanisms. Here,
      cortical excitability has been studied by paired pulse electrical stimulation,
      applied either within the MI or peripherally to the trigeminal nerve, while the
      responses were recorded bilaterally in the MI. The ratios between the amplitudes
      of the second and first evoked potentials (EPs or fEPSPs) were taken as measures
      of the inhibitory capacity in the MI ipsilateral or contralateral to the nerve
      injury. A skin wound or unilateral facial nerve exposure immediately caused a
      transient facilitation, which was followed by a reset to some level of inhibition
      in the MI on both sides. After facial nerve transection, the first relatively
      mild reduction of inhibition started shortly (within 10 min) after denervation.
      This was followed by a second step, involving a stronger decrease in inhibition,
      40-45 min later. Previous publications have proved that sensory nerve injury
      (deafferentation) induces disinhibition in corresponding areas of the sensory
      cortex. It is now demonstrated that sham operation and, to an even greater
      extent, unilateral transection of the purely motoric facial nerve
      (deefferentation), each induce extended disinhibition in the MIs on both sides.

PMID- 10886359
TI  - Corticothalamic axons contact blood vessels as well as nerve cells in the
      thalamus.
AB  - Corticothalamic axons in cats and rats were studied after labelling by
      intracortical injections of axonally transported markers. Individual axons were
      traced to their terminal branches. Many preterminal segments had a tightly spiral
      or winding course which was often closely adjacent to a thalamic blood vessel.
      Electron micrographs of such axons showed them lying immediately adjacent to the
      vascular basement membrane, without the astrocytic cytoplasm that generally
      separates neural processes from the basement membrane of vessels. The functional
      nature of this neurovascular relationship remains to be explored.

PMID- 10886360
TI  - Elevation of intradendritic sodium concentration mediated by synaptic activation
      of metabotropic glutamate receptors in cerebellar Purkinje cells.
AB  - Cerebellar Purkinje cells express both ionotropic glutamate receptors and
      metabotropic glutamate receptors. Brief tetanic stimulation of parallel fibers in
      rat and mouse cerebellar slices evokes a slow excitatory postsynaptic current in
      Purkinje cells that is mediated by the mGluR1 subtype of metabotropic glutamate
      receptors. The effector system underlying this mGluR1 EPSC has not yet been
      identified. In the present study, we recorded the mGluR1 EPSC using the whole
      cell patch-clamp technique in combination with microfluorometric recordings of
      the intracellular sodium concentration ([Na+]i) by means of the fluorescent
      sodium indicator SBFI. The mGluR1 EPSC was induced by local parallel fibre
      stimulation in the presence of the ionotropic glutamate receptor antagonists NBQX
      and D-APV and the GABAA receptor antagonists bicuculline or picrotoxin. The
      mGluR1 EPSC was associated with an increase in [Na+]i that was restricted to a
      specific portion of the dendritic tree. The mGluR1 EPSC as well as the increase
      in [Na+]i were inhibited by the mGluR antagonist S-MCPG. In the presence of NBQX,
      D-APV, pictrotoxin and TTX, bath application of the selective mGluR agonist 3,5
      DHPG induced an elevation in [Na+]i which extended over the whole dendritic field
      of the Purkinje cell. This finding demonstrates that the mGluR1-mediated
      postsynaptic current leads to a significant influx of sodium into the dendritic
      cytoplasm of Purkinje cells and thereby provides a novel intracellular signalling
      mechanism that might be involved in mGluR1-dependent synaptic plasticity at this
      synapse.

PMID- 10886361
TI  - Thermodynamic and kinetic analyses for understanding sequence-specific DNA
      recognition.
AB  - Thermodynamic and kinetic analyses of biomolecular interactions reveal details of
      the energetic and dynamic features of molecular recognition processes, and
      complement structural analyses of the free and complexed conformations. The
      recent improvements in both isothermal titration calorimetry and surface plasmon
      resonance sensoring provide powerful tools for analysing biomolecular
      interactions in thermodynamic and kinetic approaches. The thermodynamic and
      kinetic parameters obtained for binding between protein and DNA indicate the
      mechanism of specific DNA recognition, in the high-resolution structures of the
      protein-DNA complexes. The effects of temperature and ionic strength reflect the
      conformational changes of the protein and DNA molecules upon complex formation,
      including important contributions of water and solutes. When combined with
      mutational studies, the interactions can be reduced to several energetic
      contributions from individual contacts. These studies should be useful to
      determine general features of protein functions in genetic regulation.

PMID- 10886362
TI  - Bidirectional migration of SeqA-bound hemimethylated DNA clusters and pairing of
      oriC copies in Escherichia coli.
AB  - BACKGROUND: We previously found that SeqA protein, which binds preferentially to
      newly replicated hemimethylated DNA, is localized as discrete fluorescent foci in
      Escherichia coli cells. A single SeqA focus, localized at midcell, separates into
      two foci and these foci migrate abruptly in opposite directions. RESULTS: The
      present study shows that (i) appearance of SeqA foci depends on continuous DNA
      replication, suggesting that the SeqA foci represent clusters consisting of SeqA
      and newly replicated hemimethylated DNA, (ii) in a synchronous round of
      replication, a single SeqA focus at midcell separates into two foci and these
      foci abruptly migrate in opposite directions midway through replication from oriC
      to the terminus, and (iii) oriC is replicated at midcell but replicated oriC
      copies remain linked with each other at midcell for 40 min after replication at
      30 degrees C. Subsequently, the linked oriC copies separate and migrate gradually
      towards both borders of the nucleoid before cell division. CONCLUSIONS: A single
      cluster of SeqA-bound hemimethylated DNA segment separates into two clusters and
      these clusters migrate abruptly in a bipolar fashion during progress of
      replication and prior to separation of linked sister oriC copies.

PMID- 10886363
TI  - Distinct transcriptional regulation and phylogenetic divergence of human LEFTY
      genes.
AB  - BACKGROUND: Mouse lefty1 and lefty2 genes are expressed on the left side of
      developing embryos and are required for left-right determination. Here we have
      studied expression and transcriptional regulatory mechanisms of human LEFTY
      genes. RESULTS: The human LEFTY locus comprises two functional genes (LEFTY1 and
      LEFTY2) and a putative pseudogene. LEFTY1 is expressed in colon crypts. However,
      whereas LEFTY1 mRNA is present in basal cells of the crypts, LEFTY1 protein is
      localized in the apical region, suggesting that this secreted protein undergoes
      long-range transport. Human LEFTY2 possesses a left side-specific enhancer (ASE)
      like mouse lefty2; however, the LEFTY2 ASE shows markedly higher activity in the
      floor plate than does the lefty2 ASE. In contrast to mouse lefty1, which is
      expressed predominantly in the floor plate under the control of a right side
      specific silencer, human LEFTY1 is expressed mainly in left lateral plate
      mesoderm under the control of an ASE-like left side-specific enhancer. The
      presence of FAST-binding sites in the LEFTY1 enhancer (and their absence in
      lefty1) contributes to the difference. CONCLUSION: These observations suggest
      that humans and mice have acquired distinct strategies during evolution for
      determining the asymmetric expression of LEFTY and lefty genes.

PMID- 10886364
TI  - Schnurri interacts with Mad in a Dpp-dependent manner.
AB  - BACKGROUND: Decapentaplegic (Dpp) is a member of the transforming growth factor
      beta superfamily. Dpp governs various developmental processes in Drosophila
      through the transcriptional regulation of a variety of genes. Signals of Dpp are
      transmitted from the cell membrane to the nucleus by Medea and Mad, both
      belonging to the Smad protein family. Mad was shown to bind to the Dpp-responsive
      element in genes such as vestigial, labial, and Ultrabithorax. The DNA binding
      affinity of Smad proteins is relatively low, and requires other nuclear factor(s)
      to form stable DNA binding complexes. schnurri (shn) was identified as a
      candidate gene acting downstream of Dpp receptors, but its relevance to Mad has
      remained unknown. RESULTS: We characterized the biochemical functions of Shn. Shn
      forms homo-oligomers. Shn is localized in the nucleus, and is likely to have
      multiple nuclear localizing signals. Finally, we found that Shn interacts with
      Mad in a Dpp-dependent manner. CONCLUSIONS: The present results argue that Shn
      may act as a nuclear component of the Dpp signalling pathway through direct
      interaction with Mad.

PMID- 10886365
TI  - A novel RNA motif that binds efficiently and specifically to the Ttat protein of
      HIV and inhibits the trans-activation by Tat of transcription in vitro and in
      vivo.
AB  - BACKGROUND: To find a novel RNA that would bind efficiently and specifically to
      Tat protein but not to other cellular factors, we used an in vitro selection
      method and isolated a novel aptamer RNATat, a 37-mer RNA oligomer, that binds
      efficiently to the Tat protein of HIV-1. In the present study, we analysed
      various properties of aptamer RNATat, including binding kinetics, identification
      of functional groups for Tat binding, and inhibition of Tat function. RESULTS:
      The binding affinity of the isolated aptamer RNATat to Tat-1 was 133 times higher
      than that of authentic TAR-1 RNA. RNATat is composed of inverted repeats of two
      TAR-like motifs, and even though RNATat had two Tat-binding core elements, the
      interaction with Tat took place at a molar ratio of 1 : 1. Several functional
      groups of aptamer RNATat responsible for Tat binding were identified. The
      selected aptamer RNATat competed effectively for binding to Tat even in the
      presence of a large excess of TAR-1 or TAR-2 RNA in vitro, and specifically
      prevented Tat-dependent trans-activation both in vitro and in vivo. CONCLUSIONS:
      Our results indicate that a novel aptamer, RNATat, retained strong affinity for
      Tat even in the presence of a large excess of HIV TAR. RNATat binds efficiently
      to Tat proteins or peptides derived from either HIV-1 or HIV-2. Unlike TAR RNA,
      RNATat affinity does not depend upon cellular proteins such as cyclin T1, thus
      RNATat has the potential for use as a molecular recognition element in
      biosensors.

PMID- 10886366
TI  - Molecular beacon aptamer fluoresces in the presence of Tat protein of HIV-1.
AB  - BACKGROUND: We reported an aptamer, RNATat that binds to the Tat protein of HIV
      with two orders of magnitude greater (133-fold) affinity over the TAR RNA of HIV
      1 and specifically inhibits the Tat-dependent trans-activation of transcription,
      both in vitro and in vivo (demonstrated in the accompanying article, Yamamoto et
      al., this issue pp. 371-388). We now report the use of aptamer-derived oligomers
      to analyze the Tat of HIV and the possible applications of such constructs in the
      field of biosensors. RESULTS: To make new molecular beacon, we constructed two
      RNA oligomers that derived from RNATat. To one of the split RNA oligomers that
      forms a hairpin structure, the fluorophore and quencher were attached at the 5'-
      and 3'-ends, respectively. Specifically in the presence of Tat or its peptides,
      but not in the presence of other RNA binding proteins, the two oligomers undergo
      a conformational change to form a duplex that leads to relieving of fluorophore
      from the quencher, and thus a significant enhancement of the fluorescence of
      fluorescein was observed. CONCLUSION: A novel strategy for exploiting aptamers in
      the analysis of Tat (analyte) has been described. A similar strategy could be
      used to study other analytes such as proteins and small molecules. In addition,
      the molecular beacon aptamer requires half the length of target sequence (eight
      nucleotides) in comparison with molecular beacons. Thus, it is conceivable that
      we could insert an analyte-binding site into molecular beacons to convert them to
      signalling beacons.

PMID- 10886367
TI  - Interaction between neurone and microglia mediated by platelet-activating factor.
AB  - BACKGROUND: Platelet-activating factor (PAF) is a potent phospholipid mediator
      that plays various roles in neuronal function and brain development. The
      production and release of PAF in the brain has also been reported under various
      pathological conditions. However, neither the cell types and mechanism
      responsible for the synthesis of PAF nor its target cells have been fully
      identified. RESULTS: Using primary culture cells derived from rat brain and a
      very sensitive assay method for PAF, we found that PAF was synthesized in
      neurones following stimulation with glutamic acid. PAF synthesis required
      activation of NMDA receptors and subsequent elevation of intracellular calcium
      ions. Microglia, which express functional PAF receptors to a high level, showed a
      marked chemotactic response to PAF. This chemotaxis is a receptor-mediated
      process, as microglia from PAF-receptor-deficient mice did not show such a
      response. The activation of a pertussis-toxin-sensitive G-protein and mitogen
      activated protein kinase presumably plays a role in intracellular signalling
      leading to chemotaxis. CONCLUSIONS: Considering the cytoprotective and cytotoxic
      roles of microglia, PAF functions as a key messenger in neurone-microglial
      interactions.

PMID- 10886368
TI  - Modulation of TFIIH-associated kinase activity by complex formation and its
      relationship with CTD phosphorylation of RNA polymerase II.
AB  - BACKGROUND: The general transcription factor TFIIH plays important roles in
      initiation and the transition to elongation steps of transcription by RNA
      polymerase II (PolII). Both roles are dependent on the protein kinase, DNA
      dependent ATPase and DNA helicase activities of TFIIH. However, how these enzyme
      activities of TFIIH contribute to transcription has remained elusive. TFIIH
      consists of nine subunits, and one of them, Cdk7, possesses kinase activity. Here
      the substrate specificities of TFIIH and two forms of the Cdk7-containing kinase
      complex are compared, and the relationship between transcription activity and the
      TFIIH-dependent phosphorylation of the carboxy terminal domain of the largest
      subunit of PolII (CTD) is studied. RESULTS: We prepared TFIIH and two Cdk7
      containing kinase complexes, Cdk7/Cyclin H and CAK (Cdk7/Cyclin H/MAT1).
      Consistent with previous reports, CAK strongly phosphorylated Cdk2, Cdk4, CTD and
      intact PolII. In contrast, Cdk7/Cyclin H, which lacks MAT1, did not phosphorylate
      these substrates, except for weak phosphorylation of Cdk2. The kinase activity of
      TFIIH displayed stronger substrate preference for Cdk4 than did CAK. In addition,
      TFIIH phosphorylation of PolII was stimulated by TFIIE both in solution and
      during preinitiation complex formation, whereas Cdk7/Cyclin H and CAK
      phosphorylation of PolII was not. In combination with other general transcription
      factors, TFIIH, but not Cdk7/CycH or CAK, promoted transcription on a linear DNA
      template. This transcription was well correlated with TFIIE stimulated TFIIH
      phosphorylation of serine at position 5 (Ser-5) within the heptapeptide repeat of
      the PolII CTD. CONCLUSION: These results provide clues about the roles of CTD
      phosphorylation at Ser-5 in transcription.

PMID- 10886369
TI  - Genes involved in the determination of the rate of inversions at short inverted
      repeats.
AB  - BACKGROUND: Not all of the enzymatic pathways involved in genetic rearrangements
      have been elucidated. While some rearrangements occur by recombination at areas
      of high homology, others are mediated by short, often interrupted homologies. We
      have previously constructed an Escherichia coli strain that allows us to examine
      inversions at microhomologies, and have shown that inversions can occur at short
      inverted repeats in a recB,C-dependent fashion. RESULTS: Here, we report on the
      use of this strain to define genetic loci involved in limiting rearrangements on
      an F' plasmid carrying the lac genes. Employing mini-Tn10 derivatives to generate
      insertions near or into genes of interest, we detected three loci (rmuA,B,C)
      that, when mutated, increase inversions. We have mapped, cloned and sequenced
      these mutator loci. In one case, inactivation of the sbcC gene leads to an
      increase in rearrangements, and in another, insertions near the recE gene lead to
      an even larger increase. The third gene involved in limiting inversions, rmuC,
      has been mapped at 86 min on the E. coli chromosome and encodes a protein of
      unknown function with a limited homology to myosins, and some of the SMC
      (structural maintenance of chromosomes) proteins. CONCLUSIONS: This work presents
      the first example of an anti-mutator role of the sbcC,D genes, and defines a new
      gene (rmuC) involved in DNA recombination.

PMID- 10886370
TI  - Central role for cdc45 in establishing an initiation complex of DNA replication
      in Xenopus egg extracts.
AB  - BACKGROUND: In eukaryotes, chromosomal DNA is licensed to be replicated through
      the sequential loading of the origin recognition complex, Cdc6 and mini
      chromosome maintenance protein complex (MCM) onto chromatin. However, how the
      replication machinery is assembled onto the licensed chromatin during initiation
      of replication is poorly understood. RESULTS: Using Xenopus egg extracts, we have
      investigated the role of Cdc45 in the loading of various replication proteins
      onto chromatin at the onset of S phase, and found that Cdc45, which required MCM
      for its loading, was essential for the sequential loading of replication protein
      A (RPA), DNA polymerase alpha and proliferating cell nuclear antigen (PCNA) onto
      chromatin. The assembly of DNA polymerase epsilon onto chromatin required Cdc45
      but did not require DNA polymerase alpha. Analysis of nuclease-digested chromatin
      fractions shows that Cdc45 formed a stable complex with either MCM or DNA
      polymerase alpha on chromatin. CONCLUSIONS: These results demonstrate a central
      role for Cdc45 in activation of the licensed chromatin to form replication
      complexes at the onset of S phase, and suggest that Cdc45 has a dual role in the
      initiation of DNA replication: the unwinding of DNA and the recruiting of DNA
      polymerases onto DNA.

PMID- 10886371
TI  - Orientation specificity of the Lactococcus lactis Chi site.
AB  - BACKGROUND: In Escherichia coli, the Chi sequence modulates the activity of
      RecBCD, a powerful double-stranded (ds) DNA exonuclease/helicase. Chi attenuates
      RecBCD exonuclease activity and stimulates homologous recombination in an
      orientation-dependent manner. ChiEc is frequent and over-represented on its
      genome, which is thought to be related to its role in dsDNA break repair. We
      previously identified a Chi-like sequence (referred to as ChiLl) and an
      exonuclease/helicase in the Gram-positive bacterium Lactococcus lactis. ChiLl and
      RexAB are functional analogues of ChiEc and RecBCD. RESULTS: We report that ChiLl
      attenuates RexAB exonuclease activity and stimulates homologous recombination in
      an orientation-dependent manner. Analysis of ChiLl distribution on the L. lactis
      chromosome reveals that ChiLl is frequent, highly over-represented, and oriented
      with respect to the direction of replication. CONCLUSION: Our results show that a
      single orientation of ChiLl interacts with RexAB. The active orientation is
      preferentially found on the replication leading strand of the L. lactis genome,
      consistent with a primary role of ChiLl in repair of dsDNA breaks at the
      replication fork. We propose that orientation-dependence of Chi activity and over
      representation of Chi sequences on bacterial genomes may be conserved properties
      of exonuclease/helicase-Chi couples. Other properties of the Chi sequence
      distribution on the genomes might reflect more specific characteristics of each
      couple and of the host.

PMID- 10886372
TI  - The Schizosaccharomyces pombe spo6+ gene encoding a nuclear protein with sequence
      similarity to budding yeast Dbf4 is required for meiotic second division and
      sporulation.
AB  - BACKGROUND: Sporulation of the fission yeast Schizosaccharomyces pombe is a cell
      differentiation process which accompanies meiosis. The spo6+ gene was identified
      as a sporulation-specific gene, whose transcription was regulated by the forkhead
      family transcription factor Mei4. RESULTS: spo6+ encodes a protein with sequence
      similarity to Saccharomyces cerevisiae Dbf4p, which is required for the
      initiation of DNA replication. However, doubling time and cell morphology of spo6
      deletion mutants and spo6-cDNA over-expressing cells were indistinguishable from
      wild-type cells. Spliced mature mRNAs of spo6+ appeared when diploid cells
      committed to meiosis. Spo6p fused to green fluorescent protein (GFP)
      preferentially localized in a nucleus. Although spo6Delta diploids normally
      underwent premeiotic DNA replication and meiosis-I, approximately 80% of cells
      were blocked at the binucleate stage during meiosis and virtually no asci were
      formed. Anti-tubulin staining revealed that only 25% of the binucleate cells
      assembled spindle microtubules for meiosis-II. In a small number of tetranucleate
      cells, sister nuclei insufficiently separated and spindles were frequently
      fragmented. The meiosis-II arrest phenotype was exaggerated at low temperature
      and in the presence of caffeine. CONCLUSIONS: These results indicate that Spo6p
      is a novel Dbf4-related nuclear protein, which is expressed during meiosis and is
      indispensable for normal progression of meiosis-II and sporulation.

PMID- 10886373
TI  - ORC1 interacts with c-Myc to inhibit E-box-dependent transcription by abrogating
      c-Myc-SNF5/INI1 interaction.
AB  - BACKGROUND: The c-myc oncogene product (c-Myc) is a transcription factor that
      forms a complex with Max and recognizes the E-box sequence. c-Myc plays key
      functions in cell proliferation, differentiation and apoptosis. As for its
      activity towards cell proliferation, it is generally thought that c-Myc
      transactivates the E-box-containing genes that encode proteins essential to cell
      cycle progression. Despite the characterization of candidate genes regulated by c
      Myc in culture cells, these have still not been firmly recognized as real target
      genes for c-Myc. RESULTS: We found that c-Myc directly bound to the N-terminal
      region of origin recognition complex-1 (ORC1), a region that is responsible for
      gene silencing, in a state of complex containing other ORC subunits and Max in
      vivo and in vitro. Furthermore, ORC1 inhibited E-box-dependent transcription
      activity of c-Myc by competitive binding to the C-terminal region of c-Myc with
      SNF5, a component of chromatin remodelling complex SNF/Swi1. CONCLUSIONS: These
      results suggest that ORC1 suppresses the transcription activity of c-Myc by its
      recruitment into an inactive form of chromatin during some stage of the cell
      cycle.

PMID- 10886374
TI  - Ste20-like kinase (SLK), a regulatory kinase for polo-like kinase (Plk) during
      the G2/M transition in somatic cells.
AB  - BACKGROUND: Activation of the cyclin-dependent kinase cdc2-cyclin B1 at the G2/M
      transition of the cell cycle requires dephosphorylation of threonine-14 and
      tyrosine-15 in cdc2, which in higher eukaryotes is brought about by the Cdc25C
      phosphatase. In Xenopus, there is evidence that a kinase cascade comprised of
      xPlkk1 and Plx1, the Xenopus polo-like kinase 1, plays a key role in the
      activation of Cdc25C during oocyte maturation. In the mammalian somatic cell
      cycle, a polo-like kinase homologue (Plk1) also functions during mitosis, but a
      kinase upstream of Plk is still unknown. RESULTS: We show here that human Ste20
      like kinase (SLK), which is a ubiquitously expressed mammalian protein related to
      xPlkk1, can phosphorylate and activate murine Plk1. During progression through
      the G2 phase of the mammalian cell cycle, the activity of endogenous SLK is
      increased. The amount of SLK protein is decreased in quiescent and
      differentiating cells. Treatment with okadaic acid induces a phosphorylation
      dependent enhancement of SLK activity. CONCLUSIONS: We propose that SLK has a
      role in the regulation of Plk1 activity in actively dividing cells during the
      somatic cell cycle. SLK itself is suggested to be regulated by phosphorylation.

PMID- 10886375
TI  - Targeted disruption of the homeobox transcription factor Bapx1 results in lethal
      skeletal dysplasia with asplenia and gastroduodenal malformation.
AB  - BACKGROUND: NK homeobox genes have been shown to play important roles in cell
      type specification and organogenesis. Murine Bapx1, a member of NK homeobox gene
      family, is expressed in all the cartilageous tissues that undergo endochondral
      bone formation, and in gut mesentery during embryogenesis, suggesting that Bapx1
      may be a key transcription factor ragulating the development of these organs.
      RESULTS: We generated Bapx1-deficient mice by gene targeting. Bapx1-/- mice
      exhibited lethal skeletal dysplasia, with abnormal development of the vertebral
      column and some craniofacial bones, accompanied with asplenia and gastroduodenal
      malformation. We showed that the proliferative activity of the sclerotome cells,
      forming the vertebral column, was significantly reduced in Bapx1-/- embryos. The
      sclerotome cells of the mutants appeared to migrate and condense normally, but
      subsequent differentiation into the mature vertebral bodies and intervertebral
      discs were affected. The sclerotome cells in the vertebral bodies failed to
      differentiate into hypertrophic chondrocytes, as revealed by the undetected
      expression of Col10a1 and Osteopontin, and the sclerotome cells in the
      intervertebral discs failed to express the typical extracellular matrix proteins
      Col2a1, Col9a2 and aggrecan. Furthermore, we investigated the effect of loss of
      Bapx1 on the expression of some transcription factors, identified to be expressed
      in the developing sclerotome and be required for normal development of the
      vertebral column. Among them, we found that the expression of MFH-1 (mesenchyme
      forkhead-1), which was reported to regulate the proliferation and differentiation
      of sclerotome cells, was significantly reduced in ventromedial sclerotome cells
      in Bapx1-/- mice. CONCLUSION: Our analysis provided evidence that Bapx1 was
      indispensable for normal development of ventromedial structure of vertebral
      column and some of craniofacial bones, splenogenesis and morphogenesis of
      gastroduodenal tract.

PMID- 10886376
TI  - Direct imaging of phosphorylation-dependent conformational change and DNA binding
      of CREB by electron microscopy.
AB  - BACKGROUND: The second messenger cAMP stimulates the expression of numerous genes
      through the PKA-dependent phosphorylation of CREB. The cAMP-regulated
      transcription factor CREB undergoes conformational change in response to
      phosphorylation by PKA at Ser 133. The phosphorylation enables interaction
      between the kinase-inducible domain (KID) of CREB and KIX domain of CREB binding
      protein (CBP). RESULTS: To understand the activation mechanism of CREB-mediated
      gene expression, we performed the electron-microscope imaging of the
      transcription machinery. We improved the metal shadowing techniques to achieve
      higher resolution to detect phosphorylation-induced conformation change of the
      protein. Homodimer formation of CREB and the complex formation of phosphorylated
      CREB with CBP were observed under the electron microscope. The binding of the
      CREB dimer to CREs on the somatostatin and tyrosine hydroxylase promoters were
      also visualized directly and stereoscopically. CONCLUSIONS: Greatly improved
      resolution achieved by our modified metal shadowing techniques makes it possible
      to visualize that the shape of CREB homodimer was changed in phosphorylation
      dependent manner and that the promoter DNA strands containing CREs appeared to be
      bent and twisted slightly by the holding in the crevice of the CREB homodimer.
      This method may be applicable to visualize transcriptional activation process of
      nuclear receptors or general transcription machinery.

PMID- 10886377
TI  - The evolution of maladaptation.
AB  - This review contains a description of a research program for the study of
      maladaptation, defined here in terms of deviation from adaptive peaks.
      Maladaptation has many genetic causes, including mutation, inbreeding, drift,
      gene flow, heterozygote advantage and pleiotropy. Degrees of maladaptation are
      determined by genetic architecture and the relationship between the rates of
      selective, environmental change and the nature and extent of genetic responses to
      selection. The empirical analysis of maladaptation requires: (1) recognition of
      putative maladaptation, using methods from phylogenetics, teleonomy, development
      and genetics, followed by an assessment of the nature and degree of deviation
      from adaptation, using studies of natural selection and teleonomy; (2)
      determination of the causes of the deviation, using analyses of genetics,
      development, or other methods. Conditions for unambiguously identifying
      maladaptation are considerably more stringent than those for demonstrating
      adaptation and remarkably few studies have clearly identified and characterised
      maladaptative traits. A thorough understanding of the nature of phenotypic
      variation will never be achieved without an analysis of the scope and usual
      causes of maladaptation.

PMID- 10886378
TI  - Location of Shfr, a new gene that rescues hybrid female viability in crosses
      between Drosophila simulans females and D. melanogaster males.
AB  - As a rule, progeny of crosses between Drosophila simulans females and D.
      melanogaster males are formed by sterile males, because females die as embryos.
      However, populations of these species have been found that produce a certain
      frequency of viable hybrid females. We have found that 94% of the females of a D.
      simulans population from Tel Aviv gave hybrid progenies with both sexes. The
      segregation of phenotypes with different rescue success adjusts to the action of
      a single, dominant, zygotic-acting gene involved in hybrid female viability. This
      gene, which we named 'Simulans hybrid females rescue' (Shfr), is temperature
      sensitive, showing a much smaller effect as temperature increases. Reciprocal
      crosses between Tel Aviv and a nonrescue population indicate some influence of
      cytoplasm or maternal effect in rescue. Using a chromosome substitution analysis
      we have located Shfr on the second chromosome. Using synthetic lines with this
      chromosome having different segments from Tel Aviv and from a multimarker strain
      we have mapped Shfr between black (2 L-43. 0) and pearly (2 R-74.0).

PMID- 10886379
TI  - The dicentric nature of the metacentric B chromosome of Metaleptea brevicornis
      adspersa (Acridinae, acrididae).
AB  - The meiotic behaviour of a large B isochromosome of Metaleptea brevicornis
      adspersa (Acridinae, Acrididae) was studied in both sexes using conventional
      preparations and in males by silver staining of surface-spread synaptonemal
      complexes and kinetochores. In males, both arms of the B chromosome synapse at
      zygotene-early pachytene suggesting its isochromosomal nature. Both arms separate
      precociously at late pachytene and remain joined only through the formation of a
      single distal chiasma in 92.5% and 91.7% of male and female meiocytes,
      respectively. In both sexes, the B chromosome tends to migrate precociously to
      one of the spindle poles, auto-orientating at the equator in 19.2% and 16.6% of
      metaphase I cells of males and females, respectively. In males, this produces a
      high frequency of anaphase I/telophase I lagging with the consequent inhibition
      of cytokinesis and the formation of second division restitution nuclei. For a
      better understanding of the synaptic and segregation behaviour of the B
      chromosome in males, pachytene synaptonemal complex (SC) formation was studied.
      In 0B males, pachytene nuclei invariably showed 11 fully paired SCs, each one
      with a densely stained pair of terminal kinetochores, and a single axis with a
      single kinetochore corresponding to the X univalent. In 1B males, both arms of
      the B chromosome appeared fully paired in 93. 8% of the nuclei, showing complete
      asynapsis in the rest. This frequency is almost exactly the same as distal
      chiasma formation in diplotene. The centric region of the SC of the B chromosome
      had two kinetochores connected by a single axial filament of variable length. The
      dicentric nature of the B was confirmed by silver staining of kinetochores at
      metaphase I and anaphase II stages. This is the first time that a dicentric B
      isochromosome has been described. Based on these results, two alternative models
      for the origin of isochromosomes are postulated.

PMID- 10886380
TI  - Genetic variation in natural populations of mate (Ilex paraguariensis A. st.
      hil., aquifoliaceae) using RAPD markers.
AB  - This study characterized the genetic diversity of four populations of Ilex
      paraguariensis, a plant species native to South America, using random amplified
      polymorphic DNA (RAPD) markers. A total of 341 different RAPD bands were
      generated by the 15 primers analysed. High genetic variability was detected
      within each population, with an average diversity of 0.163. The within-population
      variation was large, probably as a result of the life history characteristics of
      I. paraguariensis. The average distance between individuals from each population
      was 0.392 and that between populations was 0.433, indicating a low between
      population divergence. Most bands were common to all populations and the
      population-specific bands occurred at low frequencies. Partitioning of the
      genetic diversity indicated that 85% of the variation occurred within populations
      and only 15% between populations. Although most of the variability is within
      populations, clusterings of plants in each population were observed in the
      dendrogram.

PMID- 10886381
TI  - Genetic structure of Proclossiana eunomia populations at the regional scale
      (Lepidoptera, nymphalidae).
AB  - Populations of Proclossiana eunomia (Lepidoptera, Nymphalidae) occur in middle
      Europe in patchy habitats of hay meadows along valleys or peat bogs. Samples of
      P. eunomia populations from the Ardennes region (northern France and southern
      Belgium) were analysed by allozyme electrophoresis. Patches isolated by more than
      2 km of mature forests proved genetically distinct from their neighbouring
      populations. Mantel tests and regression analysis showed that the degree of
      genetic differentiation between the 26 studied populations is related to the
      geographical distances between them. Autocorrelation analysis (Moran's I ) showed
      that allele frequencies are positively correlated for populations up to 13 km
      apart and that the genetic neighbourhood of individuals is in the range of 0.9
      km, which is in accordance with movement studies in this species conducted in the
      same area. Analysis using Wright's F-statistics revealed that the highest
      differentiation occurs between populations of the same subregion, whereas the
      whole Ardennes region is not genetically partitioned into subregions. This is
      probably because the connectivity of the network of suitable habitats has
      significantly weakened only since the 1950s, and thus subregional differentiation
      has not yet occurred.

PMID- 10886382
TI  - Genetic differentiation among populations of the beetle Bolitophagus reticulatus
      (Coleoptera: tenebrionidae) in a fragmented and a continuous landscape.
AB  - The effect of habitat fragmentation on genetic differentiation among local
      populations of the fungivorous beetle Bolitophagus reticulatus (Coleoptera:
      Tenebrionidae) was studied in two contrasting landscapes: one heavily fragmented
      with forest fragments of variable size surrounded by inhabitable agricultural
      fields, the other an old forest providing a continuous habitat. The genetic
      structure of the beetle within each of the two contrasting areas was investigated
      by means of protein electrophoresis, screening four polymorphic loci in 20
      populations from each area. In both areas there were significant genetic
      differences among local populations, but on average differentiation in the
      fragmented area was three times greater than in the continuous one, strongly
      indicating a genetic isolation effect of habitat fragmentation. These genetic
      results are in accordance with previous studies on dispersal in this species.

PMID- 10886383
TI  - The genetic contribution of single male immigrants to small, inbred populations:
      a laboratory study using Drosophila melanogaster.
AB  - This study examined the genetic contribution of single male immigrants to small,
      inbred laboratory populations of Drosophila melanogaster. Genetic contribution
      was assessed by measuring the relative frequency of immigrant marker alleles in
      the first and second generations after immigration, while controlling for any
      selection effects at the marker locus, and for the experience of male immigrants.
      When immigrants were outbred, the mean frequency of the immigrant allele was
      significantly higher than its initial frequency, in both the first and second
      generations after immigration. There was no significant change in allele
      frequency for populations receiving inbred immigrants. The increase in allele
      frequency for outbred immigrants was attributed to an initial outbred vigour
      fitness advantage of immigrant males over resident males experiencing inbreeding
      depression. Hybrid vigour of immigrant progeny and the rare-male effect did not
      have a statistically significant role in the fitness advantage of the immigrant
      allele. The results suggest that inbreeding may have a considerable impact on the
      contribution of immigrants to the genetic diversity of populations.

PMID- 10886384
TI  - Balanced vs. slightly unbalanced selection.
AB  - Balanced selection, defined as that all parents have equal contributions to the
      next generation, is expected to minimize the loss of gene diversity and thereby
      to allow a steady increase of selection response even at very advanced
      generations. In this study, balanced selection was compared with two degrees of
      slightly unbalanced selection (equal contributions from most of the families) and
      with unrestricted selection (unequal contributions) in terms of the retrieved
      response and genetic diversity consumed (group coancestry) over 30 generations of
      selection. A simulation was used varying the heritability and considering two
      population sizes and two family sizes. Results showed that a slight unbalance can
      bring a favourable relation between retrieved response and genetic diversity when
      compared to balanced selection at low and moderate heritabilities, and when small
      families and population size were assumed. The implicit constraint of a constant
      number of contributing families imposed in balanced and slightly unbalanced
      selection reduced the likelihood of gene loss compared to unrestricted selection.
      I conclude that a slight unbalance often could be more favourable than complete
      balance regarding selection efficiency, and that gain retrieved per unit of group
      coancestry declined with further unbalance.

PMID- 10886385
TI  - Genetic structure and relationships in the snail species complex Littorina arcana
      hannaford ellis, L. compressa Jeffreys and L. saxatilis (Olivi) in the British
      isles using SSCPs of cytochrome-b fragments.
AB  - Snails of the Littorina saxatilis species complex are ubiquitous and important
      members of hard shore intertidal communities in the North Atlantic. The complex
      includes L. arcana, L. compressa and L. saxatilis. We investigated species and
      population structure among these species from six locations in Ireland and
      Britain using a nonradioactive single strand conformational polymorphism analysis
      of a 375 base pair fragment of the cytochrome-b gene. Variability was high with
      38 haplotypes found in 591 individuals. The most common haplotype in L. arcana
      and L. compressa was absent from L. saxatilis and the most common haplotype in L.
      saxatilis was found in low numbers in L. arcana and L. compressa. Haplotypes
      restricted to L. arcana and L. compressa formed a cluster separate from L.
      saxatilis haplotypes in maximum parsimony and multidimensional scaling analyses.
      In analyses examining populations, L. arcana and L. compressa formed a group
      separate from L. saxatilis. Both the populations in the L. arcana/L. compressa
      group and in L. saxatilis show similar geographical structuring in that the North
      England populations were separated from a cluster of Cornwall (South-west
      England) and Irish populations. We suggested that Pleistocene sea level changes
      accounted for these congruent genetic patterns. We concluded that L. arcana and
      L. compressa are more closely related to each other than either is to L.
      saxatilis and offer this as a resolution to a previous trichotomy.

PMID- 10886386
TI  - Tracking paternal genes with DALP markers in a pseudoarrhenotokous reproductive
      system: biparental transmission but haplodiploid-like inheritance in the mite
      Neoseiulus californicus.
AB  - The complexity of some sexual reproductive systems in arthropods still leaves
      both their genetic and epigenetic determinism and their evolutionary significance
      poorly understood. Pseudoarrhenotoky is characterized by obligate fertilization
      and differential inactivation and/or elimination of paternal chromosomes in
      embryos that develop into males. Here, we investigate how the paternal genome is
      transmitted in a pseudoarrhenotokous mite, Neoseiulus californicus, using
      codominant genetic markers detected by DALP (direct amplification of length
      polymorphism). Transmission patterns of parental alleles through one and two
      generations are reported at four or five loci corresponding to four linkage
      groups. Our data provide strong evidence for selective elimination of the
      paternal genome among male tissues. Sperm contained maternal genes exclusively,
      whereas some male somatic tissues retained most if not all paternal chromosomes.
      No recombination between parental genomes prior to paternal genome elimination
      from the embryonic germ line was observed. These data allow a reinterpretation of
      previous phenotypic and cytogenetic observations in these mites, from which we
      suggest some relevant mechanistic and evolutionary implications. In addition,
      this is the first published study using polymorphic codominant loci detected by
      the recently developed DALP method.

PMID- 10886387
TI  - Genetic diversity of the epiphytic bryophyte Leucodon sciuroides in formerly
      glaciated versus nonglaciated parts of Europe.
AB  - Twelve populations of the epiphytic bryophyte Leucodon sciuroides from three
      major regions representing formerly glaciated and nonglaciated regions of Europe
      were screened for polymorphisms at 15 putative isozyme loci. The populations
      clustered into three distinct groups consisting of: (i) a single population from
      Crete, representing a cryptic unknown taxon; (ii) four Scandinavian populations
      and two populations from northern Greece; and (iii) the remaining populations
      from mainland Greece and Crete. The Scandinavian populations were genetically
      depleted compared with most Greek populations, thus fitting the expectation of
      generally lower levels of variation in formerly glaciated areas. The transition
      zone between genetically diverse and depleted populations appears to be located
      through northern Greece, coinciding with the northern limit of the Mediterranean
      region. This indicates that genetic variation was lost in populations at the
      northern limit of glacial refugia. The two groups of populations fit a progenitor
      derivative model. They also have contrasting reproductive strategies: the
      Mediterranean populations reproduce sexually, whereas the other populations
      propagate vegetatively. Epiphytic species, growing on substrates that are limited
      in space and time, appear to be especially vulnerable to loss of genetic
      variation. Lack of genetic variation and therefore low adaptability to increased
      levels of atmospheric pollution may explain why many epiphytic lichen and
      bryophytes, including L. sciuroides, are declining over much of Europe.

PMID- 10886388
TI  - Congruence between allozyme and cytochrome b gene sequence data in assessing
      genetic differentiation within the Iberian endemic Chondrostoma lemmingii
      (Pisces: cyprinidae).
AB  - To understand further the fragmentation of the hydrographical basins and the
      processes of divergence and speciation of freshwater fishes of the Iberian
      Peninsula, 10 populations of the Iberian endemic cyprinid Chondrostoma lemmingii
      were studied using 26 loci encoding 19 enzymes and the complete nucleotide
      sequence of the mitochondrial cytochrome b gene. Nuclear and mitochondrial DNA
      markers showed complete congruence in assessing the genetic differentiation among
      the samples analysed. This congruence was supported by a Mantel test in which a
      significant correlation (r=0.89) between Nei's genetic distances and sequence
      divergence (uncorrected p distances) was obtained. Diagnostic loci, Nei's genetic
      distances, and FST values, as well as the percentage of sequence divergence
      indicate that the Duero basin population accumulates the highest level of genetic
      differentiation. A moderate divergence was also observed among populations of the
      rest of the basins. Phenetic and phylogenetic relationships support the
      hypothesis that the differentiation process was not only due to hydrographical
      basin isolation but also due to an ancient endorrheism event, previous to
      hydrographical configuration, that could explain the marked differentiation of
      the Duero basin population.

PMID- 10886389
TI  - Immature B lymphocytes from adult bone marrow exhibit a selective defect in
      induced hyperexpression of major histocompatibility complex class II and fail to
      show B7.2 induction.
AB  - Mature B lymphocytes respond to antigen receptor ligation by phenotypic changes,
      including up-regulation of major histocompatibility complex class II molecules
      and expression of B7.2, which are required for initiating and sustaining a
      productive interaction with T helper cells. We have previously demonstrated that
      neonatal B cells fail to show a similar up-regulation of class II and B7.2
      expression following B-cell receptor (BCR) ligation, although these responses
      could be induced by other stimuli. Here we demonstrate that immature B cells from
      adult bone marrow exhibit even more profound defects in these responses, as they
      fail to up-regulate class II in response to either BCR ligation or interleukin-4.
      Moreover, bone marrow-derived, immature B cells could not be induced to express
      B7.2 either by receptor cross-linking or by lipopolysaccharide. These differences
      in the inducible expression of class II and B7.2 appear to be intrinsic to the B
      cells, as they were retained in purified populations of B-lineage cells and could
      not be induced in mature B cells by co-culture with bone marrow cells.
      Furthermore, short-term culture of bone marrow permitted B-cell maturation, which
      was accompanied by acquisition of responsiveness to the same stimuli as mature,
      splenic B cells. The inability of immature B cells to show these responses
      provides a molecular explanation for their reported deficiency in interacting
      with T cells. Failure of immature B cells to inducibly express B7.2 may also be
      important for the establishment of self tolerance in the B-cell compartment.

PMID- 10886390
TI  - Anti-anti-idiotypic (Ab3) antibodies that bind progesterone-11alpha-bovine serum
      albumin differ in their combining sites from antibodies raised directly against
      the antigen.
AB  - Polyclonal rabbit anti-idiotypic (Ab2) antibodies raised against the
      antiprogesterone mAb DB3 (Ab1) were used to induce an Ab3 antiprogesterone
      response in BALB/c mice. While the affinity of Ab3 sera for progesterone was 10
      50-times lower than that of DB3, their steroid-binding specificity showed
      considerable similarity to DB3. Two immunoglobulin M (IgM) Ab3 monoclonal
      antibodies (mAbs), 1A4 and 3B11, were obtained, both of which bound progesterone
      conjugated to bovine serum albumin (progesterone-BSA). 1A4 also bound free
      progesterone, although with low affinity and very broad cross-reactivity. Like
      DB3, 1A4 is encoded by a heavy-chain variable region (VH) gene segment from the
      small VGAM3.8 family, a restriction that is characteristic of antibodies raised
      against progesterone-11alpha-BSA. In contrast, 3B11 binds progesterone-11alpha
      BSA but not free progesterone and is encoded by an unrelated VH gene from the
      J558 family. The light chain variable region (VL) of 1A4 lacks the intradomain
      disulphide bridge owing to replacement of CysL23 by Tyr. Both the 1A4 and 3B11
      heavy chains have extremely short complementarity determining region (CDR) H3
      loops, comprising three and four amino acids, respectively. Modelling of the
      combining site of 1A4 from the X-ray crystallographic structure of DB3 indicates
      that the short H3 loop is a major factor in the loss of affinity and specificity
      for steroid.

PMID- 10886391
TI  - Disparate effect of beige mutation on cytotoxic function between natural killer
      and natural killer T cells.
AB  - Beige mice lack natural killer (NK) cytotoxicity, although NK cells are normally
      present. In recent studies, NK T cells have been newly identified. We therefore
      examined the number and function of NK T cells in beige mice. The number of NK T
      cells was at a normal level in the liver of beige mice. NK cytotoxicity was
      decreased in the liver of these mice, whereas NK T cytotoxicity was intact. When
      immunochemical staining for perforin was conducted, the majority of NK cells and
      the minority of NK T cells in beige mice carried a giant granule, containing
      perforin, in the cytoplasm. In the case of control B6 mice, the majority of NK
      cells and the minority of NK T cells had multiple, dispersed granules containing
      perforin. These results suggest that NK T cytotoxicity is unaffected by the beige
      mutation, owing to their cytotoxicity being mediated without the secretion system
      of perforin.

PMID- 10886392
TI  - FD-891, a structural analogue of concanamycin A that does not affect vacuolar
      acidification or perforin activity, yet potently prevents cytotoxic T lymphocyte
      mediated cytotoxicity through the blockage of conjugate formation.
AB  - FD-891 belongs to a group of 18-membered macrolides, and is a structural analogue
      of a specific inhibitor of vacuolar type H+-ATPase, concanamycin A (CMA). In our
      previous work, we have shown that CMA specifically inhibits perforin-dependent
      cytotoxic T lymphocyte (CTL)-mediated cytotoxicity through the degradation and
      inactivation of perforin, although CMA does not affect Fas ligand (FasL)
      dependent cytotoxicity. Here, we show that FD-891 potently prevents not only
      perforin-dependent but also FasL-dependent CTL-mediated killing pathways by
      blocking CTL-target conjugate formation. In contrast to CMA, FD-891 was unable to
      inhibit vacuolar acidification and only slightly decreased the perforin activity
      in lytic granules. FD-891 blocked granule exocytosis in response to anti-CD3,
      mainly owing to the lack of CTL binding to immobilized anti-CD3. The conjugate
      formation was markedly inhibited only when effector cells were pretreated with FD
      891. Consistent with these observations, fluorescence-activated cell sorter
      (FACS) analysis for cell surface receptors revealed that FD-891 significantly
      reduced the expression of the T-cell receptor (TCR)/CD3 complex. These data
      suggest that the blockage of conjugate formation and subsequent target cell
      killing might be at least partly owing to FD-891-induced down-regulation of the
      TCR/CD3 complex.

PMID- 10886393
TI  - Tetanus toxin L chain is processed by major histocompatibility complex class I
      and class II pathways and recognized by CD8+ or CD4+ T lymphocytes.
AB  - Tetanus toxin (TeNT) is a heterodimeric protein antigen, whose light chain (L) is
      translocated in the cytosol of neuronal target cells specifically to cleave its
      substrates, vesicle-associated membrane protein-2 (VAMP-2, or synaptobrevin) or
      cellubrevin. We report that the L chain behaves as a nominal antigen recognized
      by specific T-cell clones upon either class I- or II-restricted presentation.
      Three types of responses are observed: (i) a TeNT- and L-specific CD8+ T-cell
      response, that can be inhibited in a dose-dependent manner by the proteasome
      inhibitor clasto-Lactacystin beta-lactone; (ii) a CD4+ T-cell response specific
      for L but not TeNT, with recognition of a determinant processed in a chloroquine
      sensitive and brefeldin A-resistant compartment; (iii) a CD4+ T-cell response
      against both L and TeNT, with processing in a brefeldin A-sensitive compartment.
      The L chain processing was investigated in U937 cells by internalization and
      localization of L chain by separation of the cell content by differential
      centrifugation experiments. After incubation with TeNT or L chain in the presence
      of H chain, the L chain was predominantly distributed in the cytosolic fraction,
      whereas incubation with L alone led to localization in a lysosome/membrane
      fraction. The distribution of the TeNT L chain in both cytosolic and endocytic
      compartments of the antigen-presenting cell accounted for its processing by both
      class I and class II pathways. Furthermore, an epitope overlapping with the zinc
      binding region was recognized by CD4+ and CD8+ T cells.

PMID- 10886394
TI  - Generation of alphabeta T-cell receptor+ CD4- CD8+ cells in major
      histocompatibility complex class I-deficient mice upon activation of the aryl
      hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - Gene-targeted mice lacking the beta2 microglobulin gene (beta2m-/- mice), and
      hence functional major histocompatibility complex (MHC) class I molecules, do not
      develop CD4- CD8+ cells. We show here that both in vitro and in vivo treatment
      with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a trans-activating ligand of the
      endogenous aryl hydrocarbon receptor (Ah-R), bypasses the need for MHC class I
      molecules for selection into the CD4- CD8+ cell pool. When beta2m-/- dams were
      given a single dose of 50 microg of TCDD, approximately 13% of CD4- CD8+
      thymocytes could be detected in their newborn pups. In TCDD-exposed fetal thymus
      organ cultures of beta2m-/- mice, approximately 35% CD4- CD8+ thymocytes were
      detectable. About 16% of these CD4- CD8+ cells bore the alpha beta T-cell
      receptor (TCR) and approximately 33% bore CD3. Only a minority of the CD8+ cells
      were heat-shock antigen positive. The cells possessed killing activity as shown
      using the 51Cr-release assay comprising gamma delta TCR- CD4- CD8+ thymocytes
      from 3 to 4-day-old b2m-/- mice. Thus, TCDD leads to a significant increase of
      mature CD4- CD8+ thymocytes in relative and absolute numbers. High numbers of CD4
      CD8+ thymocytes developed also in organ cultures from thymi, lacking both MHC
      class I and class II molecules, exposed to TCDD. A 10-fold transient increase of
      Notch1 mRNA in thymocytes from fetal thymus organ culture, exposed for 4 days to
      TCDD, was detected in CD4+ CD8+ cells compared with controls. We suggest that
      TCDD affects thymic selection and directs the lineage commitment of CD4+ CD8+
      thymocytes towards CD4- CD8+ cells, possibly via up-regulation of the Notch1
      gene.

PMID- 10886395
TI  - In vitro T-cell activation of monocyte-derived macrophages by soluble messengers
      or cell-to-cell contact in bovine tuberculosis.
AB  - The macrophage plays a dual role in tuberculosis, promoting not only protection
      against mycobacteria, but also survival of the pathogen. Macrophages inhibit
      multiplication of mycobacteria but also act in concert with lymphocytes through
      presentation of antigens to T cells. Studies in animal and human infections have
      suggested a correlation of in vitro growth rates of mycobacteria with in vivo
      virulence, using uracil uptake to assess mycobacterial metabolism. This study
      found that blood-derived, non-activated bovine macrophages were capable of
      controlling Mycobacterium bovis bacillus Calmette-Gurin growth for up to 96 hr,
      but were permissive to intracellular growth of virulent M. bovis. The present
      investigation compared the in vitro modulation of these macrophage activities by
      cytokine-rich T-cell supernatants or cell-to-cell contact. On the one hand,
      treatment of cultured monocytes with mitogen-produced T-cell supernatants
      promoted morphological changes suggestive of an activation status, enhanced the
      antigen presentation capabilities of monocytes and up-regulated major
      histocompatibility complex class II expression. However, this activation was not
      associated with enhanced anti-M. bovis activity. On the other hand, incubation of
      infected monocytes with T-cell populations resulted in proportionally increased
      inhibition of M. bovis uracil uptake. This inhibition was also seen using cells
      from uninfected animals and indicated the necessity for cell-to-cell contact to
      promote antimycobacterial capability.

PMID- 10886396
TI  - Efficient induction of an antigen-specific, T helper type 1 immune response by
      interleukin-12-secreting fibroblasts.
AB  - To determine whether the paracrine secretion of interleukin (IL)-12 can
      efficiently convert immune responses characterized by high levels of synthesis of
      IL-4 and immunoglobulin E (IgE) into T helper 1 (Th1)-dominated responses, 3T3
      fibroblasts were stably transfected to secrete IL-12 (480 units/10(6) cells/48
      hr). Their effects on the T helper cell-mediated immune response were
      investigated in ovalbumin (OVA)-primed mice. Free mouse recombinant IL-12 was
      included as a control group. IL-12-secreting fibroblasts (3T3/IL-12) were more
      effective than free recombinant IL-12 at increasing OVA-specific interferon-gamma
      (IFN-gamma) production and decreasing OVA-specific IL-4 production in CD4+ T
      cells. In addition, injection with 3T3/IL-12 cells significantly increased anti
      OVA immunoglobulin G2a (IgG2a) levels and decreased anti-OVA IgE levels in OVA
      primed mice. This work suggests that IL-12-secreting fibroblasts can efficiently
      induce an antigen-specific Th1 response and may be beneficial in the treatment of
      diseases caused by undesirable T helper 2 (Th2)-dominated responses, including
      allergic diseases.

PMID- 10886397
TI  - Single cell analysis of cytokine expression kinetics by human CD4+ T-cell clones
      during activation or tolerance induction.
AB  - Exposure to optimal peptide antigen concentrations induces human CD4+ T-cell
      clones to proliferate and secrete various cytokines. Higher (> 10-fold optimal)
      antigen concentrations cause long-term proliferative unresponsiveness, which can
      be reversed by exogenous interleukin-2 (IL-2). We call this condition
      'tolerance'. We used intracellular cytokine staining and flow cytometric analysis
      to investigate the kinetics of interferon-gamma, tumour necrosis factor-alpha, IL
      4 and IL-5 production during the initial phase of tolerance induction. Single
      cell analysis of interferon-gamma and IL-4 or IL-5 coexpression showed functional
      heterogeneity of cloned human CD4+ T cells. Superstimulation with phorbol 12
      myristate 13-acetate and ionomycin (PI) revealed enhanced responsiveness shortly
      after tolerizing treatment, followed by reduced responsiveness. Both tolerized
      and activated T cells had similarly reduced cytokine responses when further
      stimulated with antigen during the following 48 hr, with limited enhancement
      following additional stimulation with PI. We conclude that cytokine induction is
      normally followed by a refractory phase, but that the expression of cytokines is
      enhanced in the initial phase of tolerance induction.

PMID- 10886398
TI  - Levamisole induces interleukin-18 and shifts type 1/type 2 cytokine balance.
AB  - Immune responses can be classified, according to the predominant cytokines
      involved, into type 1 (featuring interferon-gamma, IFN-gamma) and type 2
      (featuring interleukin-4, IL-4); imbalance between type 1 and type 2 cytokine
      compartments has been implicated in many human diseases. Levamisole is a drug
      with an unknown mode of action that has been used to boost immunity in infectious
      diseases including leprosy, and in some cancers. To test the hypothesis that
      levamisole acts by inducing a shift to a type 1 immune response, we used Brown
      Norway (BN) rats, which are markedly biased to type 2 responses. BN rats treated
      with levamisole showed a dose-dependent rise in serum IFN-gamma and fall in serum
      immunoglobulin E (IgE) level. Detailed analysis of cytokine gene expression
      showed upregulation of IFN-gamma and downregulation of IL-4 messenger RNA. This
      coincided with marked upregulation of IL-18, a recently characterized cytokine
      with potent activity in stimulating IFN-gamma production. IL-12 was not induced.
      Further, the type 2 response induced in BN rats by mercuric chloride was markedly
      attenuated when rats were pretreated with levamisole: there was a 2-log reduction
      in maximum serum IgE level and marked attenuation of IL-4 gene upregulation.
      These data indicate that levamisole acts by resetting the immune balance towards
      a type 1 response via induction of IL-18. Our findings provide a direction for
      development of more specific immunomodulating therapy.

PMID- 10886399
TI  - Lack of costimulation by both sphingomyelinase and C2 ceramide in resting human T
      cells.
AB  - Resting T cells require a signal transduced through their antigen-specific T-cell
      receptor (TCR) and an antigen-independent costimulatory signal in order to
      proliferate and become activated. Ligation of the CD28 receptor costimulates T
      cell proliferation and is critical to correct T-cell function. A putative
      effector of CD28-mediated costimulation is the sphingomyelinase enzyme, which
      generates the potent second messenger ceramide. We have examined the role of
      sphingomyelinase and C2 ceramide for their ability to costimulate resting human T
      cells. We observed that neither sphingomyelinase nor C2 ceramide could
      costimulate human T-cell proliferation in combination with anti-CD3 antibody,
      whereas CD80, a natural CD28 ligand, was strongly costimulatory. Surprisingly,
      both sphingomyelinase and C2 ceramide strongly inhibited the proliferation of
      resting T cells stimulated through TCR and CD28 receptors. Despite these
      inhibitory effects, neither sphingomyelinase nor C2 ceramide induced apoptosis
      and we found that upregulation of activation markers CD25 and CD69 could still
      occur in the presence of sphingomyelinase/C2 ceramide. These data indicate that
      neither sphingomyelinase nor C2 ceramide can substitute for CD28 costimulation
      and that these molecules may be involved in negatively regulating T-cell
      proliferation.

PMID- 10886400
TI  - Involvement of protein tyrosine kinases in activation of human eosinophils by
      platelet-activating factor.
AB  - Activation of human eosinophils by platelet-activating factor (PAF) involves
      multiple signal transduction pathways. Among these, protein kinase C has been
      demonstrated both to mediate respiratory burst and to suppress an alternative
      pathway of activation of respiratory burst and arachidonic acid metabolism in
      eosinophils. We utilized inhibitors of protein tyrosine kinases (PTK) to
      elucidate the role of PTK in PAF-induced activation of eosinophils. Eosinophils
      were isolated from peripheral blood of atopic donors and stimulated with PAF in
      the absence or presence of broad-spectrum PTK inhibitors-genistein or lavendustin
      A; an inhibitor of mitogen-activated protein (MAP) kinase activation-tyrphostin
      AG126; or an inhibitor of Janus kinase 2 (Jak2)-tyrphostin B42 (AG490). PAF
      induced superoxide anion (O2-*) generation, leukotriene C4 (LTC4) release,
      intracellular calcium ion mobilization and tyrosine phosphorylation of multiple
      eosinophil proteins in a concentration-dependent manner. All of these responses
      were concentration-dependently inhibited by genistein; lavendustin A also
      exhibited potent inhibition of PAF-induced LTC4 release. AG126 had no effect on
      either O2-* generation or LTC4 release, while AG490 inhibited both responses,
      albeit less effectively than genistein. We conclude that PAF activates PTK in
      human eosinophils and that this signalling pathway is involved in eliciting
      respiratory burst and leukotriene production. The specific PTK(s) involved are
      unknown but may include Jak2.

PMID- 10886401
TI  - Interleukin-15 up-regulates the expression of CD154 on synovial fluid T cells.
AB  - To investigate the role of the CD40-CD154 interaction in rheumatoid arthritis
      (RA), we analysed the expression of CD154 on CD3+ and CD4+ T cells in synovial
      fluid (SF) from patients with RA and in peripheral blood (PB) from patients and
      normal controls. As interleukin (IL)-15 is a potent activator of synovial T cells
      we wanted to study whether IL-15 also regulated the expression of CD154 on these
      T cells. Freshly isolated synovial T cells did not express significant levels of
      CD154, as evaluated using flow cytometry, whereas the expression of CD86 and
      human leucocyte antigen (HLA)-DR was significantly elevated on SF T cells when
      compared with PB T cells from patients or controls. Synovial T cells could up
      regulate their CD154 expression following activation with phorbol 12-myristate 13
      acetate (PMA) + ionomycin or anti-CD3 + anti-CD28 monoclonal antibodies (mAbs),
      but the maximal level of expression remained lower than in control T cells. IL-15
      significantly increased the expression of CD154 on SF and PB T cells from
      patients, whereas IL-2 had minimal effects. Furthermore, IL-15 induced extensive
      proliferation in SF T cells. Our results show that SF T cells up-regulate the
      expression of CD154 in the presence of IL-15, a cytokine present in the synovium
      of patients with RA. These results further emphasize the role of IL-15 in the
      pathogenesis of RA.

PMID- 10886402
TI  - The role of the Brambell receptor (FcRB) in liver: protection of endocytosed
      immunoglobulin G (IgG) from catabolism in hepatocytes rather than transport of
      IgG to bile.
AB  - The Brambell receptor (FcRB) mediates functions of both immunoglobulin G (IgG)
      transport, transmitting immunity from mother to young, and IgG protection, making
      IgG the longest surviving of all plasma proteins. Reflecting its role as
      transport receptor (termed FcRn, for neonatal rat intestine, the tissue from
      which it was first cloned), FcRB is expressed antenatally in the rabbit, mouse
      and rat fetal yolk sac and in human placental syncytiotrophoblasts, and
      neonatally in the intestinal epithelium of mice and rats. Reflecting its role as
      protection receptor (FcRp), FcRB is expressed in the vascular endothelium
      throughout life, where it protects IgG from the on-going catabolic activities of
      this tissue. FcRB detected in hepatocytes was hypothesized to mediate transport
      of IgG from serum to bile, thus potentially extending the transport expression
      (FcRn) of this receptor beyond the perinatal period. Our results show serum-to
      bile transport of IgG to be unaffected in mice functionally deleted for FcRB.
      Accordingly, the hypothesis is rejected that FcRB functions as transport receptor
      (FcRn) in liver. The default conclusion is that FcRB in hepatocytes functions as
      FcRp, serving to protect IgG from catabolism in hepatocytes that accompanies the
      endocytic activity of these cells. We conclude that there remains to date no
      evidence of an FcRn-like transport function of the Brambell receptor beyond the
      perinatal period, after which the FcRp function of the receptor predominates,
      paralleling the endocytic activities of the associated tissues.

PMID- 10886403
TI  - Activation of human Vgamma9Vdelta2 T cells by a Brucella suis non-peptidic
      fraction impairs bacterial intracellular multiplication in monocytic infected
      cells.
AB  - Human gamma delta T cells are considered to play an important role in the early
      response to infection with intracellular pathogens. Evidence has been presented
      that the percentage of gamma delta T cells with Vgamma9Vdelta2 phenotype is
      dramatically increased in the peripheral blood of patients with acute
      brucellosis. This specific gd T-cell subpopulation is known to be activated by
      small non-peptidic molecules that can either be produced by the pathogen itself
      or released from damaged cells after infection. In the present work we provide
      evidence that Vgamma9Vdelta2 T lymphocytes from peripheral blood mononuclear
      cells of healthy donors can be specifically activated by non-peptidic low
      molecular-weight compound(s) from Brucella suis lysate. Moreover, we show that
      Vgamma9Vdelta2 T cells activated by this B. suis fraction produce tumour necrosis
      factor-alpha and interferon-gamma, which reduce bacterial multiplication inside
      infected cells.

PMID- 10886404
TI  - Modulation of the immune response to DNA vaccine by co-delivery of costimulatory
      molecules.
AB  - We have investigated methods for modulating immune responses, against herpes
      simplex virus (HSV), generated from DNA vaccination by co-delivery of genes
      encoding costimulatory molecules. A strong delayed-type hypersensitivity (DTH)
      reaction was induced in mice co-injected via the intradermal (i.d.) route with a
      eukaryotic expression plasmid encoding the CD80 molecule (pCD80) and a plasmid
      encoding the glycoprotein D of the HSV-2 (pgD). Furthermore, when spleen cells
      from these mice were cultured in the presence of inactivated HSV, a significant
      increase in the expression of interleukin-2 receptor (IL-2R) was observed in the
      CD4 subset compared with mice immunized only with pgD. Analysis of cytokine
      synthesis at the single-cell level indicated that CD80 genes induce a significant
      increase in the number of interferon-gamma (IFN-gamma)-, IL-2- and IL-4-secreting
      cells in the spleen. On the other hand, co-administration of the CD80 gene via
      the intramuscular (i.m.) route did not induce an increase in the cell-mediated
      immune response. When a plasmid carrying the CD86 gene (pCD86) was co-injected
      via the i.m. route with the pgD plasmid, a small decrease in the number of IFN
      gamma-secreting cells was observed. This down-regulation of the immune response
      was also observed when eukaryotic expression cassettes for CD80 and for CD86 were
      co-administered with the pgD plasmid via the i.d. route. However, co-injection of
      pCD86 via the i.m. route produced a small increase in the number of IL-4
      secreting cells. When immunized mice were challenged intravaginally with 100
      plaque-forming units of virus, only co-injection of the CD80 gene by the i.d.
      route provoked an adjuvant effect compared with mice immunized with pgD alone. A
      reduction in the titres of HSV in vaginal washings was observed together with a
      decrease in the lesion score.

PMID- 10886405
TI  - A gut-specific serine protease from the malaria vector Aanopheles gambiae is
      downregulated after blood ingestion.
AB  - A chymotrypsin-like serine protease gene (AgChyL) was cloned from the mosquito
      Anopheles gambiae by a polymerase chain reaction (PCR)-based subtractive cDNA
      cloning strategy. AgChyL messenger RNA (mRNA) is abundant in the adult female gut
      prior to, and for 8 h following, a blood meal. During the peak of digestion, from
      12 to 24 h following a blood meal, AgChyL mRNA abundance decreased to barely
      detectable levels. AgChyL mRNA was abundant again by 48 h following a blood meal.
      Recombinant pro-AgChyL was expressed in Escherichia coli. The pro-enzyme can be
      activated by trypsin. Activated AgChyL cleaves the synthetic chymotrypsin
      substrate succinyl-L-Ala-Ala-Pro-Phe-nitroanilide, but not two other synthetic
      chymotrypsin substrates or synthetic trypsin and elastase substrates. The
      potential role of AgChyL in the coordination of An. gambiae digestion is
      discussed.

PMID- 10886406
TI  - Aedes aegypti dopa decarboxylase: gene structure and regulation.
AB  - Dopa decarboxylase converts L-dopa to dopamine, a precursor molecule for diverse
      biological activities in insects including neurotransmission and a variety of
      tanning reactions required for development, reproduction and defence against
      parasites. Herein, we report the cloning and sequencing of the Aedes aegypti Ddc
      gene, including 2.1 kb of the upstream promoter region. The transcribed region of
      the gene spans more than 16 kb and contains five exons. In situ hybridization
      localizes the blood-meal-induced ovarian transcription of this gene to the
      follicular epithelial cells surrounding individual oocytes. Ovary tissue
      transcription of Ddc is increased in response to injection of 20-hydroxyecdysone
      to levels equal to those observed for blood-fed controls, however coinjection
      with the translational inhibitor cycloheximide negates the effect, indicating an
      indirect regulatory role for this hormone. Clusters of putative ecdysone
      responsive elements and zinc-finger binding domains for the products of Broad
      Complex gene family are identified in the 5'-promoter region. These elements are
      discussed in the context of common insect Ddc regulatory mechanisms.

PMID- 10886407
TI  - Molecular cloning and expression of Tenebrio molitor ultraspiracle during
      metamorphosis and in vivo induction of its phosphorylation by 20-hydroxyecdysone.
AB  - Using a RT-PCR approach, the Tenebrio molitor homologue of Drosophila
      Ultraspiracle (TmUSP) was characterized. Its DNA binding domain shows a degree of
      identity with those of the other insect USPs. However, the ligand binding domain
      is closer to those of retinoid X receptors. Using an antibody raised against
      DmUSP, Western blot analysis of proteins from epidermis and other tissues
      revealed five immunoreactive bands, corresponding to different phosphorylated
      forms of a unique polypeptide, as shown by lambda-phosphatase treatment. The
      nuclear form of TmUSP seems unphosphorylated. An in vivo 20-hydroxyecdysone
      treatment increases considerably and rapidly the phosphorylated forms of TmUSP.
      This post-translational modification may play a role in the 20-hydroxyecdysone
      response.

PMID- 10886408
TI  - Microsatellite polymorphism in the Mediterranean fruit fly, Ceratitis capitata.
AB  - A total of forty-three simple sequence repeats (SSRs) were identified in the
      Mediterranean fruit fly (medfly) Ceratitis capitata. The most common SSR was the
      dinucleotide (TG)n/(CA)n occurring in thirty of the forty-three microsatellite
      loci. Polymorphism at ten dinucleotide markers was investigated in 122 flies from
      six natural populations sampled in the native and colonized areas. A very high
      level of allelic diversity was detected in the species range. An average of 13.6
      alleles was found over all the ten loci indicating the informativeness of SSRs as
      genetic markers for the medfly. The distribution of microsatellite polymorphism
      in the species range reflects the medfly colonization history.

PMID- 10886409
TI  - Developing SCAR markers to study predation on Trialeurodes vaporariorum.
AB  - DNA markers of Trialeurodes vaporariorum were developed to detect remains of
      these whitefly in the gut of the predator Dicyphus tamaninii. A 2400-bp DNA
      fragment of T. vaporariorum, absent in other closely related prey species and in
      the predator banding pattern, was identified by random amplified polymorphic DNA
      (RAPD) analysis. After cloning and sequencing this fragment, two pairs of
      sequence-characterized amplified region (SCAR) primers were developed, amplifying
      single bands of 2100 bp and 310 bp, respectively. Detection of T. vaporariorum
      DNA in the predator gut was only possible using the primers that amplified the
      shortest fragment. Specificity tests performed with this pair of primers showed
      the presence of the 310-bp band for T. vaporariorum in all stages.

PMID- 10886410
TI  - Mobility assays confirm the broad host-range activity of the Minos transposable
      element and validate new transformation tools.
AB  - Fast and reliable methods for assessing the mobility of the transposable element
      Minos have been developed. These methods are based on the detection of excision
      and insertion of Minos transposons from and into plasmids which are co-introduced
      into cells. Excision is detected by polymerase chain reaction (PCR) with
      appropriate primers. Transposition is assayed by marker rescue in Escherichia
      coli, using a transposon plasmid that carries a tetracycline resistance gene and
      a target plasmid carrying a gene that can be selected against in E. coli. Using
      both assays, Minos was shown to transpose in Drosophila melanogaster cells and
      embryos, and in cultured cells of a mosquito, Aedes aegypti, and a lepidopteran,
      Spodoptera frugiperda. In all cases, mobility was dependent on the presence of
      exogenously supplied transposase, and both excision and transposition were
      precise. The results indicate that Minos can transpose in heterologous insect
      species with comparable efficiencies and therefore has the potential to be used
      as a transgenesis vector for diverse species.

PMID- 10886411
TI  - Extrachromosomal transposition of the transposable element Minos occurs in
      embryos of the silkworm Bombyx mori.
AB  - To assess the ability of the transposable element Minos to act as a vector for
      genetic manipulation of the silkworm Bombyx mori, an extrachromosomal
      transposition assay based on three plasmids was performed. The three plasmids -
      helper, donor and target - were co-injected into preblastoderm embryos. Low
      molecular weight DNA was extracted from the embryos at the stage of blastokinesis
      and used to transform Escherichia coli. High frequency of transposition was
      observed in the presence of a helper plasmid possessing an intronless Minos
      transposase gene, whereas transposition did not occur in the presence of a helper
      plasmid with the intron-bearing transposase gene. Sequence analysis of the
      insertion sites showed that Minos always inserts into a TA dinucleotide. Although
      the insertions are distributed throughout the target gene, there was a preference
      for certain insertion sites. However, no consensus could be identified in the
      sequence flanking the target site. The results strongly suggest that the
      transposable element Minos has the potential to be used as a vector in the
      silkworm and probably in other lepidopteran insects.

PMID- 10886412
TI  - Molecular cloning and characterization of a putative cyclic nucleotide-gated
      channel from Drosophila melanogaster.
AB  - We have cloned a cDNA encoding a putative cyclic nucleotide-gated (CNG) channel
      from Drosophila melanogaster. The N-terminal half of the predicted protein,
      designated as CNGL, shows a high degree of sequence similarity with the known CNG
      channel proteins. CNGL has a long hydrophilic C-terminal stretch that is absent
      in other CNG channels. Northern blot analysis revealed that the messenger RNA
      (mRNA) corresponding to the size of the cloned cDNA is expressed in Drosophila
      heads. Immunolocalization studies showed that CNGL is expressed in the brain,
      including the medulla, lobulla and lobulla plate, the antennal lobe glomeruli,
      and mushroom bodies. These results suggest a possible role of the putative CNGL
      channel in the processing of visual and olfactory information in the nervous
      system of Drosophila.

PMID- 10886413
TI  - Molecular systematics of the phlebotomine sandflies of the subgenus
      Paraphlebotomus (diptera, psychodidae, phlebotomus) based on ITS2 rDNA sequences.
      Hypotheses Of dispersion and speciation.
AB  - Phylogenetic Paraphlebotomus relationships are inferred by a study based on the
      sequences of ITS2, which has been sequenced in nine Paraphlebotomus species: P.
      alexandri, P. andrejevi, P. jacusieli, P. kazeruni, P. mireillae, P. mongolensis,
      P. saevus, P. sergenti and P. similis and in two out-groups species of the
      subgenus Phlebotomus: P. papatasi and P. duboscqi. Paraphlebotomus alexandri
      appears as the sister group of all other Paraphlebotomus sandflies. Among the
      other species, three groupings are clearly highlighted: andrejevi and
      mongolensis; mireillae and saevus; jacusieli, kazeruni, sergenti and similis.
      These groupings are related to speculations about the migration of
      Paraphlebotomus from a centre of dispersion located in the Middle East sometime
      from the early Eocene to the late Miocene.

PMID- 10886414
TI  - A novel member of the RING-finger gene family associated with reproductive
      tissues of the mosquito, Aaedes aegypti.
AB  - The RING finger is a zinc-binding domain that is found in proteins from viruses,
      plants and animals. Here we report the characterization and tissue-specific
      expression of a mosquito gonadal protein gene, mgp, from the mosquito, Aedes
      aegypti. The putative gene product, MGP, contains two RING fingers, a B-box, and
      a hydrophobic core. These mosquito MGP structural motifs are highly conserved in
      proteins found in mouse and nematode. Northern blot analysis and in situ
      hybridization demonstrated the presence of multiple mgp RNA transcripts in male
      and female reproductive tissues. Expression of mgp in the ovary is constitutive,
      but an increase in message was observed in the ovaries of female mosquitoes
      previously exposed to a blood meal. These results suggest that MGP is a protein
      that might play a role(s) in mosquito gametogenesis.

PMID- 10886415
TI  - Sibling species in the Llutzomyia longipalpis complex differ in levels of mRNA
      expression for the salivary peptide, maxadilan.
AB  - Maxadilan is a small ( approximately 7 kDa) protein found in the saliva of sand
      fly species in the Lutzomyia longipalpis complex, vectors of the parasite causing
      visceral leishmaniasis, Leishmania chagasi. It is a potent vasodilator and also
      has immunomodulatory affects. Maxadilan recovered from different sibling species
      of the Lu. longipalpis complex differ in amino acid content by as much as 23%,
      however all variants possess equivalent vasodilatory activity. Therefore, the
      dramatic differences in vasodilatory activity of the saliva from different
      sibling species is probably due to differences in the amounts of maxadilan in
      their saliva. This is significant because it has been suggested that maxadilan
      may influence the pathogenesis of leishmanial infections. In this study we
      measured the amount of maxadilan messenger RNA (mRNA) per pair of salivary glands
      from individual sand flies by quantitative reverse transcription polymerase chain
      reaction (RT-PCR) using a competitive method. We report a method using the gene
      of interest, in this case maxadilan, amplified by the PCR from genomic DNA, as a
      competitor in the quantitative RT-PCR, taking advantage of differences in the
      size of these products due to the presence of an intron. Significant differences
      in amounts of maxadilan mRNA among colonies from Central and South America are
      described. We found a strong correlation between the amount of maxadilan mRNA
      detected in salivary glands of different Lu. longipalpis sibling species and
      previously described differences in the size of erythemas produced by the bite of
      these species. Therefore, variation in the amount of mRNA suggests that
      differences in the vasodilatory properties of saliva among the different sibling
      species are the result of differences in the amount of maxadilan present in the
      saliva and not differences in the potency of maxadilan peptide variants. The
      geographical distribution of species with high or low levels of maxadilan gene
      expression are concordant with the distribution of atypical cutaneous
      leishmaniasis resulting from infection with Le. chagasi, lending credence to
      earlier suggestions that maxadilan may be involved with visceralization of this
      parasite.

PMID- 10886416
TI  - The highly compact structure of the mitochondrial DNA polymerase genomic region
      of Drosophila melanogaster: functional and evolutionary implications.
AB  - The structure of a Drosophila melanogaster genomic region containing five tightly
      clustered genes has been determined and evaluated with regard to its functional
      and evolutionary relationships. In addition to the genes encoding the two
      subunits (alpha and beta) of the DNA polymerase gamma holoenzyme, the key enzyme
      for mitochondrial DNA replication, other genes contained in the cluster may be
      also involved in the cellular distribution of mitochondria and in the
      coordination of mitochondrial and nuclear DNA replication. The gene cluster is
      extremely compact, with very little intergenic space. It contains two
      bidirectional promoter regions, and particularly notable is the 5' end overlap
      detected in two of its genes, an exceptional situation in both prokaryotic and
      eukaryotic genome organization.

PMID- 10886417
TI  - Germ-line transformation of pink bollworm (Lepidoptera: gelechiidae) mediated by
      the piggyBac transposable element.
AB  - The pink bollworm, Pectinophora gossypiella, is a world-wide pest of cultivated
      cotton. In certain growing regions populations are suppressed by a sterile
      release strategy. Efforts to improve the sterile insect technique as well as our
      understanding of lepidopteran biology could benefit greatly from a germ-line
      transformation system. We report transformation of pink bollworm with a piggyBac
      transposable element carrying the enhanced green flourescent protein (EGFP)
      marker gene. This vector-marker system resulted in recovery of transgenics at a
      rate of approximately 3.5%. Integration of the transforming construct that was
      typical of piggyBac was demonstrated by Southern analysis and sequence
      determination of transposon flanks. Expression of the EGFP marker was visualized
      by fluorescent microscopy and Western Blot analysis. Maintenance of transformed
      strains indicates that the transgene segregates in a Mendelian fashion and has
      been stable over fourteen generations to date.

PMID- 10886418
TI  - Molecular identification of Anopheles minimus s.l. beyond distinguishing the
      members of the species complex.
AB  - Correct species identification is the starting point for studying the
      epidemiological role of vectors. Identification is mostly achieved using
      morphological criteria, but this fails when sibling species and species with
      overlapping morphological characters are involved. The problem with the
      identification of Anopheles minimus s. l., one of the most widespread malaria
      vectors in South-East Asia, is twofold: it is a complex of at least two
      isomorphic species, and based on morphology, members of the complex are difficult
      to distinguish from closely related species. An identification method was
      developed for An. minimus species A and C, and four related species, An.
      aconitus, An. pampanai, An. varuna and An. jeyporiensis. PCR-amplified internal
      transcribed spacer 2 (ITS2) ribonuclear DNA (rDNA) fragments were digested with
      restriction endonuclease BsiZI. Clear diagnostic banding patterns for the six
      species were obtained on agarose gels. Testing field-collected specimens from
      different regions in South-East Asia indicated that the technique will be
      applicable over a wide geographical area. From this it is clear that molecular
      identification has to focus not only on the species of complexes, but also on
      related species if they hamper the morphological identification of the 'sensu
      lato species'.

PMID- 10886419
TI  - DNA structures common for chironomid telomeres terminating with complex repeats.
AB  - Tandem repeats, 340 bp long, have been shown to terminate the chromosomes in
      Chironomus pallidivittatus and similar DNA may be used for this purpose by
      related insects. In view of the importance of Chironomus in telomere studies,
      representing in principle a third system after short repeats and Drosophila
      telomeric retrotransposons, we have investigated the related Chironomus dilutus,
      to learn what DNA structures are conserved at the chromosome ends. Interspersed
      subrepeats in the telomeric repeats, which contain a long palindrome, and a zone
      of about 100 bp of relatively constant subtelomeric DNA towards the junction to
      the telomeric DNA, are characteristic for C. dilutus as for previously
      investigated species. C. dilutus has similar subtelomeric DNA at all chromosome
      ends, but typical telomeric repeats in only seven of the pairs since the eighth
      telocentric pair contains centromere-specific repeats.

PMID- 10886420
TI  - Semen quality over a 10-year period in 22,249 men in Korea.
AB  - A retrospective study was conducted in a large population presenting with
      infertility to determine whether sperm quality has changed in Korea in the last
      10 years. We reviewed sperm concentration, motility and semen volume in 22,249
      men from whom semen was collected in our laboratory between January 1989 and
      April 1998 and analysed according to WHO (1987) guidelines. Mean age of the men
      was 32 years (range 21-40). Data were collected in healthy men with infertility.
      The mean sperm concentration was 60.5 x 10(6)/mL from 1989 to 1998. There was no
      statistically significant difference for each year (p > 0.05). Semen volume and
      sperm motility were also unchanged during the same time period. There was no
      significant association between either age or year of birth and semen quality. Of
      the total population, 4033 men (19.0%) exhibited azoospermia and 8397 men (40.
      1%) had normal semen parameters which satisfied the 1987 WHO criteria. The
      changes observed in the semen parameters analysed in this large population showed
      no evidence of deteriorating semen quality in Korea over the last 10 years.

PMID- 10886421
TI  - Duplex ultrasound evaluation of cavernosal peak systolic velocity and waveform
      acceleration in the penile flaccid state: clinical significance in the assessment
      of the arterial supply in patients with erectile dysfunction.
AB  - The aim of this paper was to establish if duplex ultrasound parameters obtained
      for assessment of the patency of cavernosal arteries in the penile flaccid state
      can give sufficient clinical information without the use of intracavernosal
      injection of vasodilatory drugs. We assessed mean cavernosal peak systolic
      velocity (PSV) in the penile flaccid state (basal PSV), and after PGE1 injection
      (dynamic PSV) in 339 unselected patients with erectile dysfunction. In 55 of
      these patients the waveform acceleration in the flaccid state was also assessed.
      The results of the study can be summarized as follows: (1) a significant
      relationship was found between basal and dynamic PSV in the 339 patients
      (r=0.477; p < 0.0001); (2) a basal PSV >12.5 cm/sec was predictive of a dynamic
      PSV >/=30 cm/sec in 129/139 (92.8%) of the patients, whereas in patients with a
      basal PSV </=12.5 a dynamic PSV both > or <30 cm/sec could be found; and (3) an
      acceleration >1 m/sec2 in the flaccid state was coupled to a dynamic PSV >30
      cm/sec in 43/46 (93.5%) of the patients independent of the basal PSV. In
      conclusion, these results suggest that the combined duplex ultrasound assessment
      of PSV and waveform acceleration in the penile flaccid state can predict arterial
      dynamic inflow in the majority (51/55; 92.7%) of patients with erectile
      dysfunction, with less time and expense and less discomfort for the patient.

PMID- 10886422
TI  - Properties of sperm separated using Percoll and IxaPrep density gradients. A
      comparison made using CASA, longevity, morphology and the acrosome reaction.
AB  - Since the withdrawal of Percoll from use in human assisted reproduction
      techniques in 1996, alternative density gradients have been sought. IxaPrep is
      one candidate that has low toxicity and can separate spermatozoa. Fractions of
      spermatozoa from normozoospermic men, separated by Percoll and IxaPrep gradient
      centrifugation, were assessed for sperm recovery, motility, morphology and the
      ability to undergo the acrosome reaction. The Percoll fractions had a
      significantly higher sperm recovery, motile count, rapid motile count, VAP, VSL,
      and VCL than those obtained using IxaPrep, both immediately after separation and
      up to 24 h later. In contrast, ALH, level of abnormal sperm morphology and the
      ability to acrosome react were not statistically different in sperm fractions
      separated using either gradient forming material.

PMID- 10886423
TI  - Functional adenosine receptors in human corpora cavernosa.
AB  - We have demonstrated that adenosine has potent relaxant activity on the rabbit
      corpus cavernosum, acting through the A2a subtype receptor for adenosine. We now
      report studies on the identification and functional characterization of adenosine
      receptors in human penile vessels. To identify A2 receptors in human corpora
      cavernosa (HCC) we performed binding studies using the selective radioligand
      [125I]PAPA-APEC in membranes from HCC. We found the presence of a single class of
      high affinity (Kd= 0.23 +/- 0.06 nM), low capacity (Bmax=134 +/- 37 fmoles/mg
      protein) binding sites. Adenosine and CGS 21680 completely displaced [125I]PAPA
      APEC binding (Kd= 146.7 +/- 64 microM and 51.52 +/- 27 nM, respectively).
      Accordingly, in functional studies adenosine relaxed phenylephrine precontracted
      HCC with an IC50=2.28 +/- 0.17 mM. The effect of adenosine was independent from
      nitric oxide (NO), and was counteracted by the A2 antagonist CGS 15943. In order
      to evaluate the in vivo effect of adenosine, increasing concentrations (6, 60,
      600 microg) of adenosine or prostaglandin E1 (PGE1) (10 microg) were injected
      into the corpora cavernosa of four healthy volunteers. Blood flow and erectile
      response were evaluated at different times by duplex sonography and visual
      inspection, respectively. It was found that adenosine increased cavernosal peak
      blood flow velocity in a time- and dose-dependent manner. The highest
      concentrations of injected adenosine elicited a response that was not
      statistically different from that of PGE1 (10 microg). However, in contrast to
      PGE1, a full or partial erection was never obtained. To further investigate the
      lack of effect of adenosine on penile tumescence (despite the substantial
      increase in cavernosal blood flow), in vitro experiments were performed on human
      deep dorsal penile veins (DDPV) obtained from surgical ligation for impotence.
      Adenosine did not affect basal tone, but it induced almost complete relaxation in
      noradrenaline-precontracted vein strips with an IC50=1.6 +/- 0.22 mM. Conversely,
      PGE1 stimulated a sustained increase in basal tone. Therefore, the lack of effect
      of adenosine on penile tumescence could be due to a simultaneous relaxing
      activity on penile corpora cavernosa and veins. In conclusion, our study
      indicates that adenosine relaxes HCC as well as penile veins without affecting
      erection, at least at the concentrations we have used. Conversely, PGE1 relaxes
      corpora cavernosa as well as adenosine but strongly stimulates vein contraction,
      allowing penile tumescence.

PMID- 10886424
TI  - Evidence for the presence of 5'-deiodinase in mammalian seminal plasma and for
      the increase in enzyme activity in the prepubertal testis.
AB  - Thyroid hormones are critical for structural and functional development of the
      testis and Sertoli cells are considered true target cells for triiodothyronine
      (T3). However, the role of thyroid hormones in the adult testis seems to be
      minimal and the mechanism by which they affect testicular function is not known.
      Due to the existing blood-testis barrier the concentration of thyroid hormones in
      seminal plasma is kept lower than in blood plasma. We have found that T3 may
      reach the testis not only from the circulation but also from local enzymic
      conversion of thyroxine to T3. The presence of the enzymic activity responsible
      for thyroxine 5'deiodination and for generating T3 locally was also found in
      boar's seminal plasma. The seminal plasma 5'-deiodinase (5'-D) appeared to be
      predominantly the propylthiouracil (PTU)-insensitive type II isoenzyme found, so
      far, in tissues where it plays a role in paracrine signalling. It contains
      selenocysteine in its molecule (inhibition by aurothioglucose), and has an
      apparent Km for reverse-T3 as substrate of 0.36 nM and a Vmax 23.8 fmol I-/mg
      protein/min. Because the seminal plasma 5'-D is partially, but uncompetitively,
      inhibited by PTU, the presence in seminal plasma of two 5'-D isoenzymes (type I
      and II) cannot be excluded. The 5'-D activity in testes increased significantly
      between week 3 and 4, and this increase was concomitant with increase in
      testicular size. The relationship between testicular weight gain and age showed a
      similar characteristic change and corresponded to the change in 5'-D activity.
      Unlike in rodents, the testis of the prepubertal pig has thyroid hormone
      receptors in Sertoli cells, and suggests that in growing piglets, testicular 5'-D
      is a key factor regulating local supply of biologically active T3, and is an
      essential factor in testicular paracrine function. The present results are the
      first demonstration and characterization of the 5'-deiodinase in seminal plasma.

PMID- 10886425
TI  - Low number of Y-chromosome deletions in infertile azoospermic men at a Swedish
      andrology centre.
AB  - Recent studies have strongly indicated that at least three regions [azoospermia
      factor (AZF) a-c] on the long arm of the Y-chromosome code for factors involved
      in spermatogenesis. In order to reveal the prevalence of microdeletions in these
      regions in a Swedish population, 192 men consecutively referred to our andrology
      unit due to infertility and showing oligozoospermia (n=53) or azoospermia (n=139)
      but no obstruction or hormonal disturbances, were investigated. For this study we
      used a multiplex polymerase chain reaction (PCR) method including 13 pairs of
      primers divided into five different primer mixes. It was found that four men, all
      with azoospermia, had deletions including part of the AZFb region and probably
      the entire AZFc region. Testis biopsies showed different morphology ranging from
      absence of germ cells to hypospermatogenisis. Of special interest was one patient
      that was first investigated 10 years ago due to primary infertility and
      oligozoospermia. Today he has developed azoospermia. It is concluded that the
      number of patients with microdeletions on the Y chromosome is rather low (less
      than 3% in highly selected azoospermic men) in our study compared to a number of
      other studies in which a 1-55% incidence have been reported. It is possible that
      ethnic differences, selection criteria and methodological aspects can contribute
      to the difference between the present and previous studies.

PMID- 10886426
TI  - Birthweight and semen characteristics.
AB  - A correlation between birthweight and sperm counts in adult life was anticipated
      because impaired fetal growth could impair replication of Sertoli cells produced
      in fetal life. Furthermore, it was expected that males born with a high
      birthweight might have impaired sperm production as they are expected to have
      been exposed to higher levels of oestrogen in fetal life. We examined these
      predictions by including midwives records for 296 Danish males that had taken
      part in studies on male fecundity for other reasons. The study provided no
      support for these expectations. If anything, males born with a birthweight of
      3000-3999 g had slightly lower sperm counts and more abnormal spermatozoa.

PMID- 10886427
TI  - Expression of green fluorescent protein under beta-actin promoter in living
      spermatogenic cells of the mouse: stage-specific regulation by FSH.
AB  - Spermatogenic cells from a mouse strain expressing enhanced green fluorescent
      protein (EGFP) under chicken beta-actin promoter were studied under living
      conditions to analyse stage- and cell-specific expression and hormonal regulation
      of the transgene. The isolated seminiferous tubules were examined by
      transillumination and the live cell squashes by phase contrast and fluorescence
      microscopy. FSH effects were measured in whole seminiferous tubules comparing
      stages I-VI, VII-VIII and IX-XII of the cycle. Beta-actin was highly expressed in
      spermatogonia, but almost no expression was found at early meiosis (leptotene
      spermatocytes). A gradual increase in translation of beta-actin was found during
      later stages of meiosis and early spermiogenesis, with a maximum in elongating
      spermatids. FSH increased the translation of beta-actin after 4 h and 24 h of
      incubation at stages I-VI, after 24 h at stages VII-VIII but not at stages IX-XII
      of the cycle. The results support the view that beta-actin plays a role in the
      nuclear elongation of spermatids and that its expression is regulated by FSH in a
      stage-specific fashion. Techniques used in this study give us new insight to
      study temporal and hormonal regulation of gene products in living spermatogenic
      cells.

PMID- 10886428
TI  - Metabolism of the putative antifertility agents 3-(36)chloro-1-hydroxypropanone
      and its dimethyl ketal in the male rat.
AB  - 3-(36)Chloro-1-hydroxypropanone (CHOP), a specific inhibitor of sperm glycolysis
      in vitro, is rapidly metabolized by the male rat to alpha-chlorohydrin, 3
      chlorolactate and the inhibitory sperm metabolite, 3-chlorolactaldehyde,
      presumably all being of the (S)-configuration. The dimethyl ketal of (36)Cl-CHOP
      [3-(36)Cl-dimethyl-CHOP] is rapidly metabolized producing identical metabolites
      and excreted radioactivity in urine at a similar rate. As neither compound
      produced diuresis, glucosuria or induced the formation of spermatocoeles,
      conditions associated with related male antifertility and antiglycolytic agents,
      they could represent an alternative means of producing (S)-3-chlorolactaldehyde
      within spermatozoa in vivo.

PMID- 10886429
TI  - Inter-observer variation in the results of the clinical andrological examination
      including estimation of testicular size.
AB  - Inter-observer variation in andrological examination by 10 clinical investigators
      from five Nordic and Baltic countries was investigated. In addition, information
      on intra-observer variation was obtained for six of the 10 investigators.
      Testicular size was measured using Prader's orchidometer and one of the
      investigators also performed an ultrasound estimate of testicular size. A highly
      significant difference (p < 0.001) between observers was found with an inter
      observer error of 16% in estimating testicular size in 23 young men. The
      difference in the estimate tended to increase with increasing testicular size.
      There was no significant intra-observer difference in two measurements performed
      on consecutive days. Only differences in median testis size, which were greater
      than 31% between measurements by two investigators, were found to be significant
      at the 5% level. The ultrasound estimate of testicular size was significantly
      lower than the orchidometer estimate, with a mean difference of 3.6 mL for the
      left testis and 4.3 mL for the right testis. Tanner staging of genitalia and
      diagnosis of a varicocele was subject to great inter-observer variation, and for
      the diagnosis of varicocele only one-third of the investigators was able to
      reproduce their results on a second examination. In conclusion, it was found that
      the clinical andrological examination of young men is subject to great inter
      observer variation. This should be kept in mind when results from different
      studies are compared as well as in daily clinical practice.

PMID- 10886430
TI  - The recruitment crisis in nursing: placing Irish psychiatric nursing in context-
      a review.
AB  - There is a decline in recruitment to pre-registration programmes in psychiatric
      nursing in Ireland. This article discusses factors that may relate to the Irish
      situation in the context of relevant international literature on nurse
      recruitment. It is noted that disciplines and courses in Ireland, such as social
      care, that engage in similar work to that of psychiatric nurses do not suffer
      from such a shortage of applicants. Whilst it is difficult to account for this
      difference, a number of factors identified from the literature are discussed. The
      need to highlight differences with general nursing and the importance of career
      guidance are seen as important in overcoming prejudices and stereotypes. From a
      review of the literature it appears that studies dedicated to recruitment to
      psychiatric nursing alone are notable by their paucity, and absent in the case of
      Ireland. Therefore, the available literature fails to fully explain the fall in
      psychiatric nurse recruitment compared to the robust recruitment position of
      social care. It is argued that dedicated research on recruitment to psychiatric
      nursing within an Irish setting is needed if a sustainable recruitment policy is
      to be implemented to reverse the long-term decline in recruitment.

PMID- 10886431
TI  - Priority-setting for nursing research in the Republic of China.
AB  - The question of how public funds for research should be allocated has led to
      participatory priority-setting in prosperous democracies like Taiwan, Republic of
      China. Useful criteria for research priorities are scientific merit, social
      benefit and feasibility. Taking a health needs approach and using these criteria,
      nearly 200 nurses from service and education in a national forum participated in
      describing research priorities. Through the group method of idea-writing, for
      clinical nursing, of high priority were assessing quality, care of the elderly,
      and preventing infectious disease. For nursing education, research addressing
      advanced role preparation and bridging nursing education and practice were
      priorities. For nursing management, research of highest priority pertained to
      economic evaluation, personnel administration, and effectiveness. These
      suggestions from the deliberation of a committed group of nurses can help shape
      future national decisions about research funding and training.

PMID- 10886432
TI  - Invisible nursing: exploring health outcomes at a global level. Relationships
      between infant and under-5 mortality rates and the distribution of health
      professionals, GNP per capita, and female literacy.
AB  - AIMS: To explore the relationship between the global distribution of health
      professionals (physicians and nurses), gross national product per capita (GNP),
      female literacy and the health outcome indicators of infant, and under-5
      mortality rates using available data from United Nations' (UN) sources. To
      consider the reliability and validity of the variables included, and the
      implications of the findings for health policy and practice, and for further
      research. DESIGN: Using a database on 155 countries, regression analyses were
      performed using GNP, female literacy, numbers of physicians per 1000 population
      and numbers of nurses per 1000 population as independent variables, and infant
      mortality (IMR) and under-5 mortality rates (u5MR) as dependent variables.
      RESULTS: Linear regression analyses give R2 values for the two mortality
      indicators (IMR and u5MR) of 63% and 66% for physicians and 51% and 52% for
      nurses. Multiple linear regression analyses reveal a more complex picture.
      Countries with high ratios of physicians and nurses to population relative to
      their GNP also tend to show low IMRs and u5MRs. However, when female literacy is
      included in the model, the majority of these outlying countries move back towards
      the regression line. Nurses disappear from the model altogether when regressed
      with physicians, GNP per capita and female literacy for both outcome indicators.
      CONCLUSIONS: Despite the acknowledged need for caution in the validity and
      reliability of the UN data sources used in the analyses, interesting positive
      relationships are identified between the input variables and mortality outputs.
      The implications for future health policy, practice and research are considered.
      These include the need for more reliable, comprehensive and up-to-date data sets.

PMID- 10886433
TI  - Chronic sorrow in parents of children with newly diagnosed diabetes: a review of
      the literature and discussion of the implications for nursing practice.
AB  - Childhood (type 1) diabetes is a chronic, life-long condition, the diagnosis of
      which may represent multiple losses for parents. Their emotional responses to the
      diagnosis have been likened to the grief reactions experienced as a result of
      bereavement through death. The practice of health professionals who work with
      these families is informed by two contrasting theoretical views of the progress
      of grief reactions; the time bound and the chronic sorrow perspectives. This
      paper provides a critical appraisal of the evidence concerning grief reactions in
      parents of children with diabetes and evaluates the extent to which this supports
      the expectations of the time bound theorists, that parents normally reach an end
      stage of the grieving process, or those of the proponents of chronic sorrow, who
      anticipate lifelong, recurring sadness. It concludes with a discussion of the
      implications of the debate for nursing practice.

PMID- 10886434
TI  - Children's community nursing services: models of care delivery. A review of the
      United Kingdom literature.
AB  - A review of the United Kingdom literature Children's community nursing (CCN)
      services in the United Kingdom (UK) have slowly become recognized as an important
      component in the care of sick children. However, as yet not every child has
      access to a CCN scheme should the need arise. In the literature there are many
      descriptions of CCN schemes set up in various parts of the United Kingdom based
      on a variety of models. This article describes six models of CCN and discusses
      the main components considered important when implementing or evaluating those
      models. Components include qualifications of the members of the team,
      communication between members of the multidisciplinary team, clinical
      responsibility, resources, willingness and ability of parents to provide care,
      and accessibility of services. The benefits and limitations of the models are
      also considered.

PMID- 10886435
TI  - Developing the research capacity of departments of nursing and midwifery based in
      higher education: a review of the literature.
AB  - The purpose of this literature review is to identify those factors which might
      affect the research capacity of departments of nursing based in higher education,
      and to make recommendations based upon the findings to enable departments to
      develop their capacity to undertake research. There is a dearth of published
      research which directly addresses this issue and therefore publications were
      reviewed which related to: the impact on nurse educators of the integration of
      nursing into higher education; nurse educators' attitudes towards research and
      their research role; analysis of the results of the 1992 and 1996 Research
      Assessment Exercises and commentaries on them; developing research within nursing
      generally; and factors affecting research productivity within nursing and related
      disciplines. The papers were analysed according to the following themes: academic
      qualifications; research skills; time available for research; motivation to
      undertake research; a culture of research; subject specialization; subject areas
      for research; research quality; and a nursing research council. The conclusions
      are first, that whilst there is a dearth of literature which relates directly to
      research capacity development in academic departments of nursing, there is much
      advice which can be drawn upon. Second, the article concludes that the factors
      affecting research capacity development are numerous and complex and it is not
      something which can only take place at the departmental level. There are also
      issues which require consideration nationally, as well as factors which depend
      upon the individual academic, and these impact upon the research capacity of
      academic departments of nursing. The factors are summarized at the end of the
      paper in the conclusions and recommendations.

PMID- 10886436
TI  - Reducing distress in first level and student nurses: a review of the applied
      stress management literature.
AB  - Following recent evidence of continuing high levels of distress in both trained
      and student nurses, a critical review of the stress reduction and stress
      management literature targeting both trained and student nurses is presented.
      Using a systematic approach, some 36 studies dating from 1980 until the present
      day were identified adopting either pre-experimental, quasi-experimental or
      experimental designs. While many work-site programmes in this series were
      successful in terms of adaptive changes in problem-solving, self-management
      skills including relaxation and interpersonal skills, affective well-being, and
      work performance, a number of design and evaluation inadequacies were identified.
      The relative lack of home-work interface or organizational level programmes to
      reduce work-related distress, and the scarcity of interventions targeting aspects
      of the work environment likely to contribute to such outcomes may have
      contributed to continuing high levels of distress in trained and student nurses.
      Recommendations regarding the future design, provision and evaluation of such
      work-site interventions include the further clarification of the structure of
      perceived stressors, and development of causal models of the stress process to
      identify the job characteristics 'causing' work-related distress. Such an
      approach would inform the design and implementation of evidence-based
      organizational level interventions augmenting strategies to target the health
      behaviour, lifestyle/risk factors and self-management skills of practitioners and
      students with attempts to amend problematic elements of the psychosocial work
      environment.

PMID- 10886437
TI  - Identifying the factors influencing minority language use in health care
      education settings: a European perspective.
AB  - The recent enhanced status of many minority languages across the European
      Community has led to increasing demands for their use within the public sector.
      This is particularly evident in health care, where, in circumstances of stress
      and vulnerability, denying opportunities for clients to communicate in their
      preferred language may place them at a personal disadvantage and compromise their
      health chances. In view of the exclusion of many minority languages from the
      public domain over the years, their re-introduction demands adaptations to health
      care education programmes in order to promote language sensitivity in practice.
      Before embarking on developments which establish such languages within the
      professional sphere, valuable insight may be gained by examining their current
      use in practice education. Furthermore, comparing their use across language
      communities enables the sharing of common experiences and furthers opportunities
      for developing networks across Europe. This paper describes an ethnographic study
      of the use, within midwifery education, of the Welsh language in north Wales, the
      Catalan language in Barcelona and the Irish language in Western Ireland. Semi
      structured interviews were conducted with key lecturers, clinical mentors and
      students across the three communities in order to determine patterns of language
      use within a range of learning environments. Focus groups were also held in order
      to confirm the findings. The data reveal many commonalities in terms of language
      use across the three settings and important factors are identified which support
      the use of minority languages in practice education. The findings are invaluable
      for guiding future bilingual initiatives across health care education programmes.

PMID- 10886438
TI  - Disposition towards critical thinking: a study of Chinese undergraduate nursing
      students.
AB  - The purpose of this study was to explore empirically whether undergraduate
      nursing students at a selected university in Hong Kong display a disposition
      towards critical thinking. The California Critical Thinking Dispositions
      Inventory (CCTDI) was used to measure the key theoretical aspects of the overall
      dispositional dimension of critical thinking. A cross-sectional descriptive
      design was used to examine 122 Chinese students who were completing their 1st,
      2nd and 3rd year of a university baccalaureate nursing programme. In the majority
      of sub-scales of CCTDI, students showed a negative disposition towards critical
      thinking. A one-way ANOVA indicated that year 3 students scored significantly
      lower than their junior counterparts (P < 0. 001). Pearson product moment
      correlation coefficient yielded a significant positive relationship between
      critical thinking dispositions and term grade point average (P < 0.05).
      Consistent with the findings of western studies, the students scored lowest on
      the truth-seeking sub-scale and highest on the inquisitiveness. Discussion of the
      findings with regard to nursing education, curriculum and research is delineated.

PMID- 10886439
TI  - Individualized care: its conceptualization and practice within a multiethnic
      society.
AB  - This paper reports on the selected findings from a larger ethnographic study of
      the provision of individualized care by district nurses to patients from
      different ethnic backgrounds. Undertaken in an English community National Health
      Service (NHS) Trust serving an ethnically diverse population, the study comprised
      two stages. First, an organizational profile of the Trust was undertaken in order
      to analyse the local policy context. Data were collected by means of in-depth
      interviews with managers and a review of policy documentation and caseload
      profiles. Second, a participant observational study was undertaken focusing on
      six district nursing teams. Purposive sampling was used to identify four teams
      with high minority ethnic caseloads and two teams with predominantly white ethnic
      majority caseloads. Interview transcripts and field notes were analysed by
      drawing upon the principles of dimensional analysis. This paper focuses upon
      aspects of the second stage, namely how the nurses' conceptualized and practised
      individualized care. Six principles underpinning the philosophy of individualized
      care expounded by the nurses were identified: respecting individuality; holistic
      care; focusing on nursing needs; promoting independence; partnership and
      negotiation of care; and equity and fairness. Each is examined in turn and
      consideration given to how they were modified in their transformation into
      practice. Some implications for patients from minority ethnic backgrounds of the
      nurses' conceptualization and practice of individualized care are discussed. The
      lack of internal consistency within the nurses' discourse, the impact of policy
      directives on care delivery and the influence of factors outside the nurses'
      control, served to illuminate the complexity whereby the ideals of individualized
      care were adjusted and reworked in the realities of everyday nursing practice.
      This in turn raised questions about the appropriateness of the current
      interpretation and practice of individualized care in a multi-ethnic society.

PMID- 10886440
TI  - South Asian patients' lived experience of acute care in an English hospital: a
      phenomenological study.
AB  - Studies on utilization of hospital services by South Asian patients in the United
      Kingdom have consistently demonstrated levels of dissatisfaction with care in
      relation to meeting religious and cultural needs, although there are few studies
      on minority ethnic patients' utilization of acute hospital services. This study
      aimed to describe and interpret from the consumer's view the 'lived experience'
      of acute hospital care from the perspectives of South Asian patients and their
      family carers. The purposive sample of 10 patients and six carers consisted of 13
      females and three males (five Hindus, six Muslims and five Sikhs) who were
      interviewed at home 2 to 3 weeks after discharge from hospital. Data were
      gathered through semi-structured interviews that were tape recorded and
      transcribed. A phenomenological approach was used, and data were analysed using
      the principles of Heideggerian hermeneutics. Five themes were identified, ranging
      from feelings of satisfaction with care, unhappy about the service, fitting-in
      strategies and post-discharge coping mechanisms. Patients seemed to want to cause
      as little disruption as possible to the ward environment and tried to fit in to
      what they refer to as an 'English place'. The findings, although not
      generalizable, offer important insights into how South Asian patients survive
      their journey through their hospital stay and have implications for the provision
      of nursing care for minority ethnic patients.

PMID- 10886441
TI  - Nurses' experiences of making decisions to call emergency assistance to their
      patients.
AB  - Patient survival often depends on decisions by nurses to call emergency
      assistance. The experiences of nurses calling emergency assistance have not been
      described. This descriptive study explored the experiences of registered nurses
      (n=32) using unstructured interviews. The main findings were that nurses
      questioned whether they were doing the 'right thing' calling the emergency team,
      sometimes collaborated with others prior to calling and most felt nervous and
      anxious. They recognized patient deterioration from feelings they had that
      something was wrong. However, they were not able 'to put their finger on it'.
      Knowing the patient and past experiences were involved in the recognition of
      deterioration. This association indicates the importance of experience in the
      development of clinical decision-making skills. Further, nurses calling emergency
      assistance need to be provided with the opportunity to debrief after calling.
      Their heavy reliance on subjective data before searching for objective data as
      outlined in the emergency calling criteria suggests that it is essential that
      nurses do not devalue or ignore concerns they may have about patients.

PMID- 10886442
TI  - Community nurses' perceptions of patient 'compliance' in wound care: a discourse
      analysis.
AB  - As part of an interview study of community nurses' perceptions of their work, 62
      staff working within the district nursing service in one English National Health
      Service Trust (grades B-H) were asked to recount occasions when they had been
      involved in wound care and to discuss the ways in which working with patients who
      required such care could be either enhanced or made difficult. A large number of
      respondents expressed the view that non-compliance could pose serious problems
      for the management of wounds. Data relating to compliance are presented here and
      are interpreted in the light of discourse analysis, an approach which permits the
      researcher to focus on the meanings underlying the communications of research
      participants and to interpret those meanings in the light of social and cultural
      mores and influences. The authors found that non-compliance could be explained by
      nurses in a number of different ways. These ranged from passive resistance, which
      could be due to ignorance or lack of motivation, through overt refusal, to
      deliberate interference in order to prolong treatment. It also seeks to outline
      some of the factors that appear to motivate the nurses' desire to achieve
      compliance.

PMID- 10886443
TI  - Suicide and self-harm in in-patient psychiatric units: a study of nursing issues
      in 31 cases.
AB  - A significant number of incidents of suicide and self-harm occur whilst patients
      are in receipt of care as in-patients. This audit comprises 31 cases which were
      referred to the first author for expert opinion, each case being the subject of
      legal action brought by patients and/or their families. The cases were referred
      from 31 different NHS trusts across England. All concerned suicide/serious self
      harm in people in receipt of in-patient care. The aims of this audit were to
      carry out a detailed assessment of the 31 individual cases, so as to provide a
      nursing dimension to already established enquiries in this area and also to
      examine whether specific issues might be the subject of more systematic research.
      Further, this paper aims to provide some insights in the area of litigation,
      where nurses are becoming increasingly involved. The same broad approach to
      information-gathering and analysis was used, comprising a systematic review of
      case records, trust policies, expert reports and, where appropriate, inquest
      transcriptions. The sample comprised 12 suicides and 19 cases of serious self
      harm. Factors associated with these events include: being male, having a dual
      diagnosis of mental illness and drug/alcohol abuse, and age between 21 and 30
      years. Of the 12 deaths, five occurred in hospital, four by hanging and one by
      drowning. The audit highlighted environmental factors associated with these
      events which, arguably, could be simply addressed. There was a considerable
      variation in the content and quality of observation policy and practice. The
      results of this audit point to the need for further research but, above all,
      provide evidence requiring urgent action by the Department of Health regarding
      the setting of national standards.

PMID- 10886444
TI  - The expression of sexuality in people with psychosis: breaking the taboos.
AB  - While mental health professionals should recognize that people suffering from
      schizophrenia have sexual and relationship requirements, there appears to be a
      failure to address adequately the subject of human sexuality, particularly in the
      area of psychosocial rehabilitation. The broad aim of this small study was to
      identify the sexual and relationship needs of people being cared for in hospital
      and preparing for a return to community living. The objectives of the study were
      to discover the clients' sexual expressions in the past and present, and to try
      to elicit hopes and aspirations for the future. An attempt was made to uncover
      some of the obstacles to the expression of sexuality and explore some of the
      clients' subjective experiences of the issues. The number of respondents was 11
      from a possible 15. Data were collected through: a questionnaire on demographic
      characteristics; an adapted version of a questionnaire investigating the
      determinant factors of sexual behaviour through life; and a semi-structured
      interview devised to elicit subjective experiences regarding sexual expression.
      The findings show that people with psychotic illness are prepared to discuss
      issues relating to sex and relationship matters. No interviews had to be
      prematurely terminated. No exacerbations of symptoms were noted. All of the
      respondents showed an openness to discuss a range of intimate feelings. Most
      respondents seemed hopeful about the opportunity to form intimate and fulfilling
      relationships in the future. A drive towards more rigorous holistic nursing
      assessments and appropriate psychosocial responses is proposed.

PMID- 10886445
TI  - Caring for adolescent females with anorexia nervosa: registered nurses'
      perspective.
AB  - This phenomenological study was undertaken to explore in depth the experiences of
      registered nurses caring for adolescent anorexic females within paediatric wards
      of general hospitals in Victoria, Australia. A qualitative design underpinned by
      the philosophy of Edmund Husserl was employed for this study. Audio taped in
      depth interviews with five registered nurses working within the public health
      care system were conducted. Using Colaizzi's procedural steps of analysis, six
      themes of meaning were explicated. They were: (a) personal core values of nurses;
      (b) core values challenged; (c) emotional turmoil; (d) frustration; (e) turning
      points; and (f) resolution. These themes, when taken together, described the
      essence of the journey undertaken by registered nurses who cared for adolescent
      anorexic females. The findings of this study indicated that there is a need for
      extensive registered nurse preparation, on-going support, and development of
      education programmes to enable registered nurses to care for these patients with
      greater understanding. Further, the participants identified the need for new care
      regimes and protocols to be developed that incorporated new ways of thinking.
      They also expressed a desire to be have greater involvement in the planned care
      of their patients.

PMID- 10886446
TI  - Learning dementia care in three contexts: practical training in day-care, group
      dwelling and nursing home.
AB  - During the period 1996-1999, 18 licensed practical nurses (LPNs) received
      specialized training to become caregivers and mentors in the field of dementia
      care at the Silvia Home Foundation in Stockholm, Sweden. The aim of the study was
      to illuminate how the trainees utilized their practical training to learn about
      dementia care. The trainees gained practical training within three care models
      for elderly persons with dementia. The three forms of care and the context for
      practical training included the school's integrated day-care, a group dwelling
      and a nursing home. The findings show that the trainees made use of each training
      context in a similar fashion but there were differences between the contexts. A
      perspective of human dignity characterized the day-care. This was an opportunity
      for the nursing philosophy taught by the programme to be put to practical use,
      and for reflection and experiences pertaining to the individual patient to be
      developed. In the group dwelling, the trainees encountered patients with
      different forms of dementia and studied how the care-giving could be adapted to
      the individual patient's symptoms - the disease perspective. In the nursing home,
      the trainees chose a staff perspective in which they focused on organization,
      management and working conditions as well as staff attitudes and the effects of
      these factors on patient care.

PMID- 10886447
TI  - Reactions of nurses and therapists in mainstream health services to contact with
      people who have learning disabilities.
AB  - Government policy in the United Kingdom is to make the National Health Service
      accessible to all citizens, including those who hitherto may have relied on
      specialist services. It is recognized that the attitudes of health professionals
      can be a major influence in making this happen. To date there has been a paucity
      of research studies involving nurses and therapists, two of the largest groupings
      of health care workers. The present study contrasted the reactions of nurses and
      therapists to their contact with people who have learning disabilities, with
      those of staff working in specialist services for this client group, and with
      students who are not involved in health services. Over 1000 respondents - mainly
      university students on undergraduate or post-graduate courses - completed a
      written questionnaire. Although nurses and therapists had significantly less
      contact with people who had learning disabilities during their work than did
      staff in specialist services, there were no differences in terms of contact in
      personal life. In both instances their contacts were higher than those reported
      for non-healthcare students. However both nurses and therapists were
      significantly less confident in working with a patient who had learning
      disabilities as opposed to one with physical disabilities. By contrast,
      willingness for social contacts did not vary across the four groups although
      respondents with previous personal contact were significantly more willing for
      this than those with no prior contact. The results confirm that the form of
      contact is a more salient variable on staff attitudes than contact per se. Hence,
      changed reactions are more likely to come about from successful contacts in a
      work rather than social environment. The implications are discussed for initial
      and post-qualifying training courses, especially for suitable placement
      experiences. Suggestions are made for future research that focuses on increasing
      the expertise and confidence of nurses and therapists in working with patients
      who have learning disabilities.

PMID- 10886448
TI  - The health-related quality of life of patients suffering from the late effects of
      polio (post-polio).
AB  - In Sweden alone, there are today approximately 10 000-16 500 polio survivors.
      Between 60% and 80% experience new symptoms several years after the initial
      attack of poliomyelitis. The aims of this study were to investigate and describe
      the self-rated health-related quality of life and functional status of a group of
      Swedish patients with post-polio, to investigate whether any differences within
      the group could be related to demographic or disease-specific data and to compare
      the post-polio patients with individuals sampled from the general population.
      Data were obtained by using two questionnaires, the Swedish Health-Related
      Quality of Life Questionnaire (SWED-QUAL) and the Sickness Impact Profile (SIP).
      A total of 150 patients, 86 women and 64 men with median age 61 (20-82) years,
      were consecutively included. The study showed that the patients mainly reported
      that their physical, functional status was affected by their post-polio
      condition. Factors found to be associated with the physical, functional status
      were age and the number of parts of the body affected by the polio. On comparing
      the post-polio patients with two samples from the Swedish general population, it
      was found that the patients reported a poorer functional status and health
      related quality of life. The women with post-polio reported more pain, as
      compared with both the men with post-polio and the women in the general
      population sample. The family life of the patients - in contrast to their
      physical abilities - did not seem to be affected by the new deteriorating
      condition. It is concluded that, owing to the wide range of symptoms, the
      patients with post-polio need care and support from multidisciplinary teams,
      including nurses and occupational therapists.

PMID- 10886449
TI  - A description of the nursing role in stroke rehabilitation.
AB  - A theoretical description of the nursing role in stroke rehabilitation remains
      elusive in the literature. The United Kingdom strategy for health service
      development will increasingly require nurses from all clinical specialities to
      collaborate with other health care professionals and stakeholders to evaluate the
      services they provide. In stroke rehabilitation, an understanding of the
      contribution that nursing makes is essential, if that collaboration is to be
      effective. This paper details a study undertaken to describe the nature of the
      nursing role in stroke rehabilitation, and the factors that shape this role. A
      reflective enquiry was used to enable the collection of data grounded in the
      realities of clinical practice. Study participants were qualified nursing staff
      (n=13) working in a rehabilitation unit in the north-west of England. A total of
      35 in-depth reflections were obtained for analysis. Three role categories were
      identified in the data: the nurse as care giver, facilitator of personal recovery
      and care manager. Sub-categories of nursing intervention were identified within
      each category, together with anticipated outcomes and contextual features that
      shaped the category. The results of the study were verified by a purposive sample
      of nursing staff from the rehabilitation unit.

PMID- 10886450
TI  - The extent of nursing research utilization in general medical and surgical wards.
AB  - There has been extensive speculation about the lack of research utilization in
      nursing but little attempt to quantify this phenomenon outside of North America.
      The current demands for evidence-based practice necessitate research utilization
      as one element of the process. As part of a larger project, this study aimed to
      describe the extent of research utilization by registered nurses in general
      medical and surgical wards in the Scottish Health Service. A postal survey was
      conducted for nurses to self-report their level of utilization of 14 research
      based practices. The 14 practices represented examples of direct, indirect and
      methodological utilization of research. A research utilization score was
      constructed for each of the 14 practices and a total mean score constructed for
      all 14 practices. A random two-stage stratified sampling resulted in a total
      sample of 936 nurses from 25 hospitals. A 73% response rate was achieved. The
      total mean research utilization score for all nurses across all 14 nursing
      practices suggests that on average, nurses had heard, believed in and were
      beginning to use the practices. The sampling technique over-represents nurses in
      large hospitals and charge nurses, hence a weighting calculation on all scores
      was completed. There was little difference in weighted and unweighted scores.
      Scores on individual practices ranged from 60% (405/680) of nurses never having
      heard of a practice to 85% (574/680) always using a practice. This approach
      provides a valid and reliable method of assessing the extent of nursing research
      utilization. In several of the practices, nurses are making significant attempts
      at research-based practice. The level of research utilization compares favourably
      with research completed in North America and provides a baseline for United
      Kingdom and other country studies.

PMID- 10886451
TI  - Frequency of and indications for wholly compensatory nursing care related to
      enteral food intake: a secondary analysis of the Belgium National Nursing Minimum
      Data Set.
AB  - This study describes the frequency of and indications used for total feeding
      assistance and tube feeding in a national representative sample of Belgian
      hospital patients (n = 421 314). Data from the 1990 national minimum nursing data
      registration was used. Orem's self-care model was used to describe and categorize
      types of nursing care and related indications. The scope of wholly compensatory
      nursing care was limited to total feeding assistance and tube feeding. This type
      of nursing care is indicated when self-care agency is undeveloped or cannot be
      used and when self-care demands are significantly increased. Based on review of
      the literature, hypotheses to indicate nursing care were formulated and tested.
      Wholly compensatory nursing care related to enteral food intake is given to 14.4%
      of the total patient population in Belgian hospitals. If self-care demand
      increases due to malnutrition, then this is an indication for total feeding
      assistance. If self-care agency decreases due to blindness, mental retardation,
      disorientation or upper extremity dysfunction, then this is also an indication
      for total feeding assistance. If self-care agency decreases due to impaired
      chewing, then this is an indication for tube feeding. This study has generated
      the first representative national nursing statistics about total feeding
      assistance and tube feeding in hospitals.

PMID- 10886452
TI  - Understanding the nature of errors in nursing: using a model to analyse critical
      incident reports of errors which had resulted in an adverse or potentially
      adverse event.
AB  - Human errors are common in clinical practice, but they are under-reported. As a
      result, very little is known of the types, antecedents and consequences of errors
      in nursing practice. This limits the potential to learn from errors and to make
      improvement in the quality and safety of nursing care. The aim of this study was
      to use an Organizational Accident Model to analyse critical incidents of errors
      in nursing. Twenty registered nurses were invited to produce a critical incident
      report of an error (which had led to an adverse event or potentially could have
      led to an adverse event) they had made in their professional practice and to
      write down their responses to the error using a structured format. Using Reason's
      Organizational Accident Model, supplemental information was then collected from
      five of the participants by means of an individual in-depth interview to explore
      further issues relating to the incidents they had reported. The detailed analysis
      of one of the incidents is discussed in this paper, demonstrating the
      effectiveness of this approach in providing insight into the chain of events
      which may lead to an adverse event. The case study approach using critical
      incidents of clinical errors was shown to provide relevant information regarding
      the interaction of organizational factors, local circumstances and active
      failures (errors) in producing an adverse or potentially adverse event. It is
      suggested that more use should be made of this approach to understand how errors
      are made in practice and to take appropriate preventative measures.

PMID- 10886453
TI  - 'Scraps': hidden nursing information and its influence on the delivery of care.
AB  - What nurses commonly describe as 'scraps' are defined as the personalized
      recordings of information that is routinely made on any available piece of paper
      (hence scraps) or in small notebooks. The use of scraps is common in practice and
      has been noted in research from across the globe. Drawing on an empirical study
      it is argued that scraps are a unique combination of personal and professional
      knowledge that informs the delivery of care. The overall aim of the study was to
      discover how nurses define and communicate information about patients and the
      delivery of care to each other on an elderly care unit. The processes by which
      information was constructed and the organizational structure and interactions
      that influenced this were also identified. The research design was an
      ethnographic one that involved: observations of formal nursing end of shift
      reports (23 handovers) and informal interactions between nurses (146 hours);
      interviews (n + 34) with registered nurses, student nurses and nursing
      auxiliaries; and analysis of written records. Data were collected from five acute
      elderly care wards at a district general hospital in the south of England. A
      grounded theory analysis was undertaken which revealed that scraps may have a
      significant role in the communication of information and the delivery of care.
      Therefore a categorization of scraps within three main themes was undertaken.
      First, the analysis revealed the processes involved in the construction of
      scraps. Second, the content and role of scraps in influencing the delivery of
      care was exposed. Finally, the potentially confidential nature of scraps and
      consequent problems of storage and disposal was recognized. The findings are
      discussed in relation to a suggested model of the interrelationship between
      paperwork, scraps, handovers and the delivery of nursing care. It is concluded
      that scraps are significant in facilitating nursing care and that this should be
      recognized in research, education and practice.

PMID- 10886454
TI  - Sharing the evidence: clinical practice benchmarking to improve continuously the
      quality of care.
AB  - It is unacceptable for health care professionals to acquiesce quietly to
      inconsistencies in the quality of health care received by patients. In the United
      Kingdom, the introduction of clinical governance has formalized the expectation
      that professionals' practice will meet recognized standards of care consistently.
      It is being stated that all available evidence is being used to identify national
      standards of excellence. This will inform professionals not only of expected
      outcomes but of also the structures and processes that need to be in place to
      support the attainment of such outcomes. Clinical practice benchmarking is one
      continuous quality improvement approach, which is being used by paediatric units
      in 27 National Health Service Trusts in the north-west of England to promote the
      utilization of available evidence in to practice. The evidence base for
      benchmarks of best practice is considered continuously using a hierarchy of
      evidence. This clarifies the different evidence available, upon which benchmarks
      or standards of excellence can be based, but reinforces the kudos awarded
      quantitative research evidence within health care. Once benchmarks have been
      agreed, benchmarking activity supports practitioners in a continuous cycle of
      comparison and sharing that is aimed at ensuring that children and their families
      receive evidence-based care, wherever they are admitted in the north-west of
      England.

PMID- 10886455
TI  - Development and testing of the Family Caregiving Factors Inventory (FCFI) for
      home health assessment in Taiwan.
AB  - This paper describes the development and psychometric testing of the Family
      Caregiving Factors Inventory (FCFI). Data were collected from 97 caregivers of
      frail elders in Taiwan to examine the validity and reliability of the four FCFI
      scales: caregiving resources, caregiver self-expectations, caregiving task
      difficulty, and knowledge of the care receiver. Acceptable test-retest and
      internal consistency reliabilities were found, though inter-rater reliability was
      unsatisfactory for caregiving task difficulty and knowledge of the care receiver
      scales. Testing of hypothesized relationships between the FCFI and related
      variables supported the construct validity of the FCFI. Confirmatory factor
      analysis with good overall model fits also supported the construct validity of
      the FCFI scales. In its present form, the FCFI can facilitate home health
      assessment and problem identification for families with frail elders. Studies
      with larger samples are needed to further verify the measurement models.

PMID- 10886456
TI  - Nursing, empathy and perception of the moral.
AB  - Over the last 15-20 years we have witnessed a dramatic interest in the moral
      domain of clinical practice. There has also been a growing focus on the patient
      as an individual whose individuality and perspective must be respected. It is
      argued in this paper that a key to both these concerns is a consideration of the
      role of empathy in both perceiving the moral aspects and issues of practice, and
      in providing adequate support for patients. In this paper the meaning and
      components of empathy are discussed in the context of human receptivity and
      preconditions of moral performance. However, we also draw attention to empirical
      studies which suggest that even following adequate educational preparation, if
      the clinical environment and the structures within which care is delivered are
      not supportive, the practitioner's ability to perceive the moral is limited. In
      such circumstances, patients are in danger of receiving less than appropriate
      care - from both the moral and professional perspective.

PMID- 10886457
TI  - Stigma of visible and invisible chronic conditions.
AB  - Nurses deliver care to people with various forms of chronic illnesses and
      conditions. Some chronic conditions, such as paraplegia, are visible while
      others, such as diabetes, are invisible. Still others, such as multiple
      sclerosis, are both visible and invisible. Having a chronic illness or condition
      and being different from the general population subjects a person to possible
      stigmatization by those who do not have the illness. Coping with stigma involves
      a variety of strategies including the decision about whether to disclose the
      condition and suffer further stigma, or attempt to conceal the condition or
      aspects of the condition and pass for normal. We present a beginning framework
      that describes the relationship between the elements of stigma and the decision
      to disclose or hide a chronic condition based on its visibility or invisibility.
      The specific aims were to combine the results from a meta-study on qualitative
      research with a review of the quantitative literature, then develop a theoretical
      framework. Although an understanding of how patients cope with stigmatizing
      conditions is essential for nurses who aim to deliver comprehensive
      individualized patient care, there is little current literature on this subject.
      The relationship between visibility and invisibility and disclosure and non
      disclosure remains poorly understood. A framework to facilitate a deeper
      understanding of the dynamics of chronic illnesses and conditions may prove
      useful for practice.

PMID- 10886458
TI  - Interactive model of women's stressors, personality traits and health problems.
AB  - Theories have linked various stressors with health problems, and some studies
      have identified personality traits that enhance health. However, few studies have
      examined the interaction among women's stressors, personality traits and their
      health. This retrospective study (1996-1997) analysed the effects of women's
      major stressors and personality traits on symptoms of health problems, and
      developed a model of women's health based on the interaction among these factors.
      A convenience sample of 300 women aged between 18 and 66 years completed a
      questionnaire that measured three types of stressors, eight personality traits
      and 40 symptoms of health problems. Principle components and factor analyses
      identified the best items to measure the stressors, traits and problems. New
      reduced data subsets were constructed for classification tree analyses to
      identify the effects of stressors and personality traits on women's health. Women
      with medium or high stressors and low assertiveness, low hardiness, or the
      inability to express their feelings, were more likely to report physical symptoms
      than women who were stronger in these personality traits. Also, women with medium
      or high stressors and low to medium trust or love relationships were very likely
      to report high emotional symptoms, as were women with high trust or love, who did
      not express their feelings. An interactive model of women's health was supported.
      The amount of women's stressors and their personality traits may increase or
      diminish their stress response and affect their health. Nurses can identify women
      with high stressors and unhealthy personality traits that increase their risk for
      stress-related illnesses, and assist these women to modify their stressors or
      personality traits to enhance their health.

PMID- 10886459
TI  - Pulmonary heart disease--the need for evidence-based management.

PMID- 10886460
TI  - Treatment of acute otitis media in patients with a reported penicillin allergy.
AB  - Otitis media occurs commonly in children, and is usually treated with an
      antibiotic. In this case report, amoxicillin was prescribed for a 6-year-old boy
      suffering from acute otitis media. As he had previously experienced a rash after
      the administration of a penicillin, the medication order was switched from
      amoxicillin to trimethoprim/sulfamethoxazole (TMP/SMX). In an effort to determine
      whether or not this intervention was appropriate, references were found using
      Medline, International Pharmaceutical Abstracts and the Cochrane Library. Issues
      to be addressed included the need for antibiotics in acute otitis media, the
      comparative efficacy and tolerability of antimicrobial agents and the reliability
      of reported penicillin allergies. Amoxicillin and TMP/SMX were found to be first
      line agents in the treatment of acute otitis media owing to their efficacy,
      safety and cost, with neither drug being significantly better than the other. The
      need to treat otitis media with antibiotics remains controversial. Reported
      penicillin allergies were found to be an unreliable indicator of a potentially
      serious reaction. In conclusion, it was found that treatment with TMP/SMX was an
      appropriate intervention.

PMID- 10886461
TI  - Cytochrome P450 2E1: its clinical and toxicological role.
AB  - Cytochrome (CYP) P450 2E1 is clinically and toxicologically important and it is
      constitutively expressed in the liver and many other tissues. In contrast to many
      other CYP isoenzymes, indisputable evidence for a functionally important
      polymorphism of CYP2E1 in the human population is lacking. CYP2E1 metabolizes a
      wide variety of chemicals with different structures, in particular small and
      hydrophobic compounds, including potential cytotoxic and carcinogenic agents. In
      addition, chlorzoxazone and trimethadione metabolism are good CYP2E1 probes for
      liver disease in vivo and in vitro. In the future, methods for fully analysing
      the function of CYP2E1 using knockout mice will be established. This article
      reviews recent advances in our understanding of the role of human CYP2E1 in drug
      metabolism.

PMID- 10886462
TI  - Therapeutic outcomes monitoring by community pharmacists for improving clinical
      outcomes in asthma.
AB  - OBJECTIVE: To determine the effect of enhanced therapeutic monitoring by
      community pharmacists on clinical outcomes of a convenience sample of asthma
      patients. METHODS: A one-year intervention study with scheduled visits and follow
      ups at baseline, 4, 8, 12 and 24 months using a pre/post-test design, with a
      small convenience sample of 28 study patients, who performed their own controls.
      Outcomes measured were the severity of asthma symptoms, changes in the number of
      patients having peak expiratory flow (PEF) values below 85% or 70% of the
      optimal, changes in daily asthma medication and number of patients needing
      courses of oral steroids. RESULTS: A positive change was noticed in all the
      measures used, most clearly in the severity of asthma symptoms. During the
      intervention, mean scores of three out of five symptom measures improved
      significantly. Twenty-two (79%) patients had a net improvement in one or more
      asthma symptom indicators. The number of patients with PEF values below 85% of
      the optimal decreased from seven to four at 12 months. The number of patients
      having courses of oral steroids for asthma decreased. More than half (57%) of the
      patients had changes in their daily asthma medication. The effects lasted partly
      over one year after the intervention. CONCLUSIONS: The results of this study
      suggest that pharmacist intervention can have a positive effect on clinical
      outcomes of asthma patients. The results need to be confirmed with a study using
      a randomized controlled design.

PMID- 10886463
TI  - Use of 0.75 mg Levonorgestrel for postcoital contraception in Thailand.
AB  - OBJECTIVE: This study identified the pattern of Levonorgestrel (LNG) use and self
      reported side-effects among Thai women in Songkla. METHOD: The eligible subjects
      were 100 Thai women who had used 0.75 mg LNG at least once in the past 12 months.
      The participants completed a questionnaire at the survey sites, which were seven
      pharmacies and five shopping malls. RESULTS: Eight percent of LNG users had never
      used any contraceptive methods other than day count and withdrawal. Thirty-nine
      percent took more than four tablets of LNG per month, which was the limit
      instructed in the label. Only 3% used LNG for emergency situations such as having
      unprotected intercourse or burst condom. At least 22% of subjects took LNG
      according to instructions which were last revised 2 years earlier. The study also
      revealed poor knowledge among the users on side-effects and limit of drug use.
      Compared to the previous studies, this study found a higher incidence of side
      effects. Forty-four percent of subjects experienced cycle disturbances and 32%
      nausea, respectively. CONCLUSION: The Thai FDA should seriously consider
      requiring manufacturers to revise labels of LNG to be consistent with those
      recommended by WHO.

PMID- 10886464
TI  - Theophylline pharmacokinetics with concomitant steroid and gold therapy.
AB  - BACKGROUND: Theophylline has been used for several decades in the treatment of
      asthma. In recent years, however, with the appreciation of the importance of
      inflammation in the pathogenesis of asthma, new therapeutic approaches have
      arisen, including beta2-agonists, steroid and nonsteroidal anti-inflammatory
      drugs, such as gold salts. OBJECTIVE: In the present work we studied the kinetic
      behaviour of theophylline administered concomitantly with methylprednisolone
      (steroid compound) and auranofin (oral gold) in six adult female patients.
      METHOD: Drug concentration data for patients under routine care were collected.
      The kinetic analysis (Bayesian Approach) was done using two different commercial
      software packages, PKS (Abbott Diagnostics) and CAPCIL (SIMKIN Inc., courtesy of
      Dade-Behring). A one-compartment open model with first-order absorption (ka for
      PKS=0. 5/h; ka for CAPCIL=0.3/h ) and first- order elimination. Default CL, t1/2
      and Vd values were used for each program was assumed. The measured and predicted
      theophylline concentrations were used to calculate percentage prediction errors
      defined as %PE=[(predicted conc. - measured conc.)/measured conc.] x 100. A
      linear regression analysis was also carried out for the observed concentrations
      and those predicted by each method (PKS vs. CAPCIL). RESULTS: The predicted
      concentrations indicating persistently over-predicted the observed theophylline
      serum levels (results expressed as median and interquartile range; %PE for
      PKS=58.1 [37.1-126.0]; %PE for CAPCIL=34.0 [12.5-93.8]). The regression analysis
      confirmed the same tendency, showing an intercept significantly different from
      zero using both PKS and CAPCIL. CONCLUSION: The results suggest a possible
      interaction between theophylline and auranofin. Both PKS and CAPCIL failed to
      predict theophylline serum levels based exclusively on population pharmacokinetic
      parameters. The lower observed concentrations than expected have obvious
      implications in practice. Periodic theophylline serum determinations are
      advisable until further studies provide the necessary clarification about the
      kinetic profile of theophylline in patients taking concomitant steroids and gold
      salts.

PMID- 10886465
TI  - Pharmacogenetics and psychopharmacotherapy.
AB  - Response to drugs can vary between individuals and between different ethnic
      populations. The biological (age, gender, disease and genetics), cultural and
      environmental factors which contribute to these variations are considered in this
      review. The most important aspect is the genetic variability between individuals
      in their ability to metabolize drugs due to expression of 'polymorphic' enzymes.
      Polymorphism enables division of individuals within a given population into at
      least two groups, poor metabolisers (PMs) and extensive metabolisers (EMs) of
      certain drugs. The two most extensively studied genetic polymorphisms are those
      involving cytochrome P450 2D6 (CYP2D6) and CYP2C19. CYP2D6 metabolizes a number
      of antidepressants, antipsychotics, beta-adrenoceptor blockers, and
      antiarrhythmic drugs. About 7% of Caucasians and 1% of Asians are PMs of CYP2D6
      substrates. CYP2C19 enzyme participates in the metabolism of omeprazole,
      propranolol and psychotropic drugs such as hexobarbital, diazepam, citalopram,
      imipramine, clomipramine and amitriptyline. The incidence of PMs of CYP2C19
      substrates is much higher in Asians (15-30%) than in Caucasians (3-6%).
      Variations in metabolism of psychotropic drugs result in variations in their
      pharmacokinetic parameters. This may lead to clinically significant intra- and
      inter-ethnic differences in pharmacological responses. Such variations are
      discussed in this review. Differential receptor-mediated response may play a role
      in ethnic differences in responses to antipsychotics and tricyclic
      antidepressants, but such pharmacodynamic factors remain to be systematically
      investigated. The results of studies of ethnic differences in response to
      psychopharmacotherapy appear to be discrepant, most probably due to limitations
      of study design, small sample size, inadequately defined study sample, and lack
      of control of confounding factors. The clinical value of understanding
      pharmacogenetics is in its use to optimize therapeutic efficacy, to prevent
      toxicity of those drugs whose metabolism is catalysed by polymorphic isoenzymes,
      and to contribute to the rational design of new drugs. Finally, applications and
      impact of pharmacogenetics in the field of psychopharmacotherapy are discussed.

PMID- 10886466
TI  - Effect of oral contraceptives on the urinary excretion of biochemical markers
      indicating vasoactive action.
AB  - OBJECTIVE: In the present study the effect of two contraceptive pills, i.e.
      Neorlest, containing ethinylestradiol and norethisterone acetate, and Valette,
      containing ethinylestradiol and the new progestin dienogest, was investigated on
      the urinary excretion of vasoactive markers. As markers prostacyclin and its
      antagonist thromboxane, cGMP, serotonin, and the vasorelaxing mediators relaxin
      and urodilatin were measured. METHOD: 30 women received Neorlest and 33 women
      Valette in a randomized, open, parallel-group study design. Nocturnal urine was
      collected before treatment and during cyclic treatment after 6 and 11 weeks.
      RESULTS: For prostacyclin, the ratio of prostacyclin to thromboxane, relaxin and
      urodilatin significant increases compared to the pretreatment values were
      observed with Valette within 11 weeks treatment. For the markers cGMP and
      serotonin both contraceptive pills showed a tendency to an increase of the renal
      excretion after 11 weeks treatment. No significant differences between the two
      pills were observed, except in the case of the ratio of prostacyclin to
      thromboxane, which showed a significant, clear-cut enhancement with Valette.
      CONCLUSION: These results indicate that contraceptive pills may stimulate the
      production of vasodilative markers, an effect which can be attributed most likely
      to the oestrogenic component of the pill. The progestogenic component of the pill
      may elicit an impact on this oestrogen-induced vasodilation, which, however,
      seems to be minimized in the case of the new compound dienogest, a C-19 progestin
      with antiandrogenic properties.

PMID- 10886467
TI  - Is enough attention being given to the adverse effects of corticosteroid therapy?
AB  - BACKGROUND: Although the corticosteroids are valuable anti-inflammatory and
      immunosuppressive agents, they also possess many potential adverse effects,
      especially with continued use. In particular, long-term corticosteroid exposure
      carries a significant risk of osteoporosis. AIM: To review the use of
      corticosteroids in patients presenting to the major teaching hospital in
      Tasmania, Australia; principally to determine whether patients receiving long
      term corticosteroid therapy were being monitored for loss of bone mineral density
      and offered preventive therapy for osteoporosis. METHODS: A retrospective review
      of the medical records for 212 consecutive patients admitted to the medical wards
      of the hospital over a 5-month period and receiving treatment with either oral or
      inhaled corticosteroids, was performed. An extensive range of demographic and
      clinical variables was recorded for each patient. Patients were also questioned
      about diet and exercise, and whether they had undergone tests for measuring bone
      mineral density or blood glucose. RESULTS: The median age of the patients was 69
      years (range: 15-90 years) and 58% were female. Over half (53%) of the patients
      were on oral corticosteroids only, with 26% using inhaled corticosteroids only,
      and 21% on both oral and inhaled corticosteroid therapy. The most common
      conditions for which patients were receiving corticosteroid therapy were asthma
      (37% of patients), chronic obstructive pulmonary disease (33%) and rheumatoid
      arthritis (17%). The most commonly used oral corticosteroid was prednisolone
      (93%), the median daily dose was 10 mg prednisolone equivalent, and the median
      duration of oral corticosteroid treatment was 50 weeks. Disregarding short
      courses, the median duration of oral corticosteroid treatment was 104 weeks.
      Almost one-third (31%) of the patients receiving oral corticosteroid treatment
      had been taking the equivalent of 7.5 mg prednisolone daily for at least 6
      months. Only 11% of all patients on oral corticosteroids and 21% of those who had
      been taking oral corticosteroids for at least one year had documented evidence of
      bone mineral density testing being performed in the past in the hospital. Only
      21% of all patients on oral corticosteroids and 31% of those who had been taking
      oral corticosteroids for at least one year were receiving medication for
      osteoporosis prevention, and only 15% of women over 45 years of age and on oral
      corticosteroid therapy were taking hormone replacement therapy. Only about half
      of the patients on long-term systemic corticosteroid therapy had either
      documented evidence in their hospital medical records, or were aware, of having
      undergone blood glucose testing in the preceding 12 months. CONCLUSION: More
      attention to the prevention and monitoring of possible adverse effects of long
      term corticosteroid therapy is warranted. Guidelines covering preventive measures
      and treatment options for corticosteroid-induced osteoporosis need to be
      considered routinely when using these agents.

PMID- 10886468
TI  - Confidence of academic general internists and family physicians to teach
      ambulatory procedures.
AB  - OBJECTIVE: To evaluate and compare the readiness of academic general internal
      medicine physicians and academic family medicine physicians to perform and teach
      13 common ambulatory procedures. DESIGN: Mailed survey. SETTING: Internal
      medicine and family medicine residency training programs associated with 35
      medical schools in 9 eastern states. PARTICIPANTS: Convenience sample of full
      time teaching faculty. MEASUREMENTS AND MAIN RESULTS: A total of 331 general
      internists and 271 family physicians returned completed questionnaires, with
      response rates of 57% and 65%, respectively. Academic generalists ranked most of
      the ambulatory procedures as important for primary care physicians to perform;
      however, they infrequently performed or taught many of the procedures. Overall,
      compared with family physicians, general internists performed and taught fewer
      procedures, received less training, and were less confident in their ability to
      teach these procedures. Physicians' confidence to teach a procedure was strongly
      associated with training to perform the procedure and performing or precepting a
      procedure at least 10 times per year. CONCLUSIONS: Many academic general
      internists do not perform or precept common adult ambulatory procedures. To
      ensure that residents have the opportunity to learn routine ambulatory
      procedures, training programs may need to recruit qualified faculty, train
      current faculty, or arrange for academic specialists or community physicians to
      teach these skills.

PMID- 10886469
TI  - Confidence of graduating internal medicine residents to perform ambulatory
      procedures.
AB  - OBJECTIVE: To evaluate the training of graduating internal medicine residents to
      perform 13 common ambulatory procedures, 3 inpatient procedures, and 3 screening
      examinations. DESIGN: Self-administered descriptive survey. SETTING: Internal
      medicine training programs associated with 9 medical schools in the eastern
      United States. PARTICIPANTS: Graduating residents (N = 128); response rate, 60%.
      MEASUREMENTS AND MAIN RESULTS: The total number of procedures performed during
      residency, importance for primary care physicians to perform these procedures,
      confidence to perform these procedures, and helpfulness of rotations for learning
      procedures were assessed. The majority of residents performed only 2 of 13
      outpatient procedures 10 or more times during residency: simple spirometry and
      minor wound suturing. For all other procedures, the median number performed was 5
      or fewer. The percentage of residents attributing high importance to a procedure
      was significantly greater than the percentage reporting high confidence for 8 of
      13 ambulatory procedures; for all inpatient procedures, residents reported
      significantly higher confidence than importance. Continuity clinic and block
      ambulatory rotations were not considered helpful for learning ambulatory
      procedures. CONCLUSIONS: Though residents in this sample considered most
      ambulatory procedures important for primary care physicians, they performed them
      infrequently, if at all, during residency and did not consider their continuity
      clinic experience helpful for learning these skills. Training programs need to
      address this deficiency by modifying the curriculum to ensure that these skills
      are taught to residents who anticipate a career in primary care medicine.

PMID- 10886470
TI  - Successful lecturing: a prospective study to validate attributes of the effective
      medical lecture.
AB  - OBJECTIVE: In a study conducted over 3 large symposia on intensive review of
      internal medicine, we previously assessed the features that were most important
      to course participants in evaluating the quality of a lecture. In this study, we
      attempt to validate these observations by assessing prospectively the extent to
      which ratings of specific lecture features would predict the overall evaluation
      of lectures. MEASUREMENTS AND MAIN RESULTS: After each lecture, 143 to 355 course
      participants rated the overall lecture quality of 69 speakers involved in a large
      symposium on intensive review of internal medicine. In addition, 7 selected
      participants and the course directors rated specific lecture features and overall
      quality for each speaker. The relations among the variables were assessed through
      Pearson correlation coefficients and cluster analysis. Regression analysis was
      performed to determine which features would predict the overall lecture quality
      ratings. The features that most highly correlated with ratings of overall lecture
      quality were the speaker's abilities to identify key points (r =.797) and be
      engaging (r =.782), the lecture clarity (r =.754), and the slide
      comprehensibility (r =.691) and format (r =.660). The three lecture features of
      engaging the audience, lecture clarity, and using a case-based format were
      identified through regression as the strongest predictors of overall lecture
      quality ratings (R2 = 0.67, P = 0.0001). CONCLUSIONS: We have identified core
      lecture features that positively affect the success of the lecture. We believe
      our findings are useful for lecturers wanting to improve their effectiveness and
      for educators who design continuing medical education curricula.

PMID- 10886471
TI  - The work lives of women physicians results from the physician work life study.
      The SGIM Career Satisfaction Study Group.
AB  - OBJECTIVE: To describe gender differences in job satisfaction, work life issues,
      and burnout of U.S. physicians. DESIGN/PARTICIPANTS: The Physician Work life
      Study, a nationally representative random stratified sample of 5,704 physicians
      in primary and specialty nonsurgical care (N = 2,326 respondents; 32% female,
      adjusted response rate = 52%). Survey contained 150 items assessing career
      satisfaction and multiple aspects of work life. MEASUREMENTS AND MAIN RESULTS:
      Odds of being satisfied with facets of work life and odds of reporting burnout
      were modeled with survey-weighted logistic regression controlling for demographic
      variables and practice characteristics. Multiple linear regression was performed
      to model dependent variables of global, career, and specialty satisfaction with
      independent variables of income, time pressure, and items measuring control over
      medical and workplace issues. Compared with male physicians, female physicians
      were more likely to report satisfaction with their specialty and with patient and
      colleague relationships (P <.05), but less likely to be satisfied with autonomy,
      relationships with community, pay, and resources (P <.05). Female physicians
      reported more female patients and more patients with complex psychosocial
      problems, but the same numbers of complex medical patients, compared with their
      male colleagues. Time pressure in ambulatory settings was greater for women, who
      on average reported needing 36% more time than allotted to provide quality care
      for new patients or consultations, compared with 21% more time needed by men (P
      <.01). Female physicians reported significantly less work control than male
      physicians regarding day-to-day aspects of practice including volume of patient
      load, selecting physicians for referrals, and details of office scheduling (P
      <.01). When controlling for multiple factors, mean income for women was
      approximately $22,000 less than that of men. Women had 1.6 times the odds of
      reporting burnout compared with men (P <.05), with the odds of burnout by women
      increasing by 12% to 15% for each additional 5 hours worked per week over 40
      hours (P <.05). Lack of workplace control predicted burnout in women but not in
      men. For those women with young children, odds of burnout were 40% less when
      support of colleagues, spouse, or significant other for balancing work and home
      issues was present. CONCLUSIONS: Gender differences exist in both the experience
      of and satisfaction with medical practice. Addressing these gender differences
      will optimize the participation of female physicians within the medical
      workforce.

PMID- 10886472
TI  - Who is at risk of nondetection of mental health problems in primary care?
AB  - OBJECTIVE: To determine patient and provider characteristics associated with
      increased risk of nondetection of mental health problems by primary care
      physicians. DESIGN: Cross-sectional patient and physician surveys conducted as
      part of the Medical Outcomes Study. PARTICIPANTS: We studied 19,309 patients and
      349 internists and family physicians. MEASUREMENTS AND MAIN RESULTS: We counted
      "detection" of a mental health problem whenever physicians reported, in a
      postvisit survey, that they thought the patient had a mental health problem or
      that they had counseled or referred the patient for mental health. Key
      independent variables included patient self-reported demographic characteristics,
      health-related quality of life (HRQOL), depression diagnoses according to the
      Diagnostic and Statistical Manual of Mental Disorders, and physician demographics
      and proclivity to provide counseling for depression. Logistic regression
      analysis, adjusted for HRQOL, revealed physicians were less likely to detect
      mental health problems in African Americans (odds ratio [OR], 0.63; 95%
      confidence interval [CI], 0.46 to 0.86), men (OR, 0.64; 95% CI, 0.54 to 0.75),
      and patients younger than 35 years (OR, 0.61; 95% CI, 0.44 to 0.84), and more
      likely to detect them in patients with diabetes (OR, 1.4; 95% CI, 1.0 to 1.8) or
      hypertension (OR, 1.3; 95% CI, 1.1 to 1.6). In a model that included DSM-III
      diagnoses, odds of detection remained reduced for African Americans as well as
      for Hispanics (OR, 0.29; 95% CI, 0.11 to 0.71), and patients with more-severe DSM
      III diagnoses were more likely to be detected. Physician proclivity toward
      providing counseling for depression influenced the likelihood of detection.
      CONCLUSIONS: Patients' race, gender, and coexisting medical conditions affected
      physician awareness of mental health problems. Strategies to improve detection of
      mental health problems among African Americans, Hispanics, and men should be
      explored and evaluated.

PMID- 10886473
TI  - Cervical cancer screening in the urgent care setting.
AB  - OBJECTIVE: To determine the feasibility of cervical cancer screening in an urgent
      care clinic. DESIGN: Prospective randomized trial. SETTING: Public teaching
      hospital. PATIENTS: Women presenting to the urgent care clinic whose evaluation
      necessitated a pelvic examination were eligible for participation. Women who had
      a hysterectomy, had a documented Pap test at our institution in the past year,
      did not speak English or Spanish, or had significant vaginal bleeding were
      excluded. Women presenting to the gynecology clinic for a scheduled Pap test were
      used as a comparison group for rates of follow-up, Pap smear adequacy, and Pap
      smear abnormalities. INTERVENTIONS: Women randomized to the intervention group
      had a Pap test performed as part of their pelvic examination, while women in the
      usual care group were encouraged to schedule an appointment in the gynecology
      clinic at a later date. The women in the two groups completed identical
      questionnaires regarding cervical cancer risk factors and demographic
      information. MEASUREMENTS AND MAIN RESULTS: Ninety-four (84.7%) of 111 women in
      the intervention group received a Pap test, as compared with 25 (29%) of 86 in
      the usual care group (P <.01). However, only 5 (24%) of 21 women with abnormal
      Pap smears in the intervention group received follow-up compared with 6 (60%) of
      10 women seen during the same time period in the gynecology clinic for self
      referred, routine annual examinations (P =.11). Pap smears obtained in the urgent
      care clinic were similar to those in the gynecology clinic with regard to
      abnormality rate (22.3% vs 20%; P =.75, respectively) and specimen adequacy (67%
      vs 72%; P =.54, respectively). CONCLUSIONS: Urgent care clinic visits can be used
      as opportunities to perform Pap test screening in women who are unlikely to
      adhere to cervical cancer screening recommendations. However, to accrue the full
      potential benefit from this intervention, an improved process to ensure patient
      follow-up must be developed.

PMID- 10886474
TI  - Blood cholesterol screening influence of fasting state on cholesterol results and
      management decisions.
AB  - OBJECTIVE: To compare fasting and nonfasting total and high-density lipoprotein
      (HDL) cholesterol values in adults and to determine how closely classification
      into risk groups for coronary heart disease based on nonfasting blood tests
      compares with classification based on fasting studies. DESIGN: Cross-sectional
      study. SETTING: A community hospital general internal medicine clinic. PATIENTS:
      One hundred eighty-one patients at least 20 years of age receiving medical care
      at a community hospital general internal medicine clinic. INTERVENTIONS: Total
      and HDL cholesterol levels were measured twice in each patient within 7 days,
      once while not fasting and once after a minimum 12-hour fast. MEASUREMENTS AND
      MAIN RESULTS: Fasting and nonfasting total and HDL cholesterol values were
      compared, patients were classified into desirable, borderline-high, and high
      cholesterol groups on the basis of fasting and nonfasting blood studies. There
      were small, statistically significant but clinically insignificant differences in
      fasting and nonfasting results for total cholesterol. Nonfasting HDL cholesterol
      levels were similar to fasting HDL levels. The agreement in classification of
      patients into desirable and high-cholesterol groups between fasting and non
      fasting blood testing was 86.7% and 89.5%, respectively. In the borderline-high
      group, for whom levels of HDL cholesterol are important in determining subsequent
      management, there was 95% agreement between fasting and nonfasting HDL
      cholesterol results. Only a small fraction of the patients were classified into
      lower-risk groups by the nonfasting assessment, creating the potential for less
      rigorous monitoring and treatment of their cholesterol status than if fasting
      results were utilized. These findings were confirmed in this study also for the
      subgroups of men aged 35 years and older and women aged 45 years and older.
      CONCLUSIONS: Screening nonfasting adults for total and HDL cholesterol is
      appropriate for making decisions about primary prevention of coronary heart
      disease.

PMID- 10886475
TI  - Cost-effectiveness of strategies for primary prevention of nonsteroidal anti
      inflammatory drug-induced peptic ulcer disease.
AB  - OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of
      peptic ulcer disease by 5- to 7-fold in the first 3 months of treatment. This
      study examined the relative cost-effectiveness of different strategies for the
      primary prevention of NSAID-induced ulcers in patients that are starting NSAID
      treatment. MEASUREMENTS AND MAIN RESULTS: A decision analysis model was developed
      to compare the cost-effectiveness of 6 prophylactic strategies relative to no
      prophylaxis for patients 65 years of age starting a 3-month course of NSAIDs: (1)
      testing for Helicobacter pylori infection and treating those with positive tests;
      (2) empiric treatment of all patients for Helicobacter pylori; (3) conventional
      dose histamine2 receptor antagonists; (4) high-dose histamine2 receptor
      antagonists; (5) misoprostol; and (6) omeprazole. Costs were estimated from 1997
      Medicare reimbursement schedules and the Drug Topics Red Book. Empiric treatment
      of Helicobacter pylori with bismuth, metronidazole, and tetracycline was cost
      saving in the baseline analysis. Selective treatment of Helicobacter pylori,
      misoprostol, omeprazole, and conventional-dose or high-dose histamine2 receptor
      antagonists cost $23,800, $46,100, $34,400, and $15,600 or $21,500 per year of
      life saved, respectively, relative to prophylaxis. The results were sensitive to
      the probability of an ulcer, the probability and mortality of ulcer
      complications, and the cost of, efficacy of, and compliance with prophylaxis. The
      cost-effectiveness estimates did not change substantially when costs associated
      with antibiotic resistance of Helicobacter pylori were incorporated. CONCLUSIONS:
      Several strategies for primary prevention of NSAID-induced ulcers in patients
      starting NSAIDs were estimated to have acceptable cost-effectiveness relative to
      prophylaxis. Empirically treating all patients for Helicobacter pylori with
      bismuth, metronidazole, and tetracycline was projected to be cost-saving in older
      patients.

PMID- 10886476
TI  - Physicians' reports of focused expertise in clinical practice.
AB  - Little is known about the prevalence of focused expertise (special areas of
      expertise within a clinical field) among physicians, yet such expertise may
      influence how care is delivered. We surveyed general internists, pediatricians,
      cardiologists, infectious disease specialists, and orthopedic surgeons to
      describe the prevalence of focused expertise and identify associated physician
      and practice characteristics. About one quarter of generalists and three quarters
      of specialists reported a focused expertise within their primary specialty.
      Hospital-based physicians more often reported such expertise, and physicians
      reimbursed by capitation less often reported expertise. Learning how focused
      expertise affects processes and outcomes of care will contribute to decisions
      about physician training and staffing of medical groups.

PMID- 10886477
TI  - Labeling smokers' charts with a "smoker" sticker: results of a randomized
      controlled trial among private practitioners.
AB  - We randomly assigned private practitioners (n = 393) to receiving, by mail, a box
      of "Smoker" stickers and a recommendation to label smokers' charts with these
      stickers, or to no intervention. Twenty percent of the physicians reported using
      the stickers and applying them on 43% of their smoking patients' charts. The
      intervention had no impact on physician reports of the proportion of smokers
      advised to quit smoking, but physicians who reported using the stickers stated
      that they advised more smokers to quit after the intervention (89%) than before
      (80%, P =.02). Thus, self-reports by physicians indicated that use of the
      stickers was associated with an increased proportion of smokers advised to quit.
      However, overall, the intervention did not modify physicians' behavior.

PMID- 10886478
TI  - Long-term outcomes after deep vein thrombosis: postphlebitic syndrome and quality
      of life.
AB  - In this review, we critically assess the literature on the incidence of
      postphlebitic syndrome, risk factors for its occurrence, available therapeutic
      options, and its effects on quality of life. As well, we describe available tools
      to measure postphlebitic syndrome. Recent prospective studies indicate that
      postphlebitic syndrome, a chronic, potentially disabling condition characterized
      by leg swelling, pain, venous ectasia, and skin induration, is established by 1
      year after deep vein thrombosis (DVT) in 17% to 50% of patients. The only
      prospectively identified risk factor for its occurrence is recurrent ipsilateral
      DVT. In the sole randomized study available, daily use of elastic compression
      stockings after proximal DVT reduced the incidence of postphlebitic syndrome by
      50%. Treatment options for established postphlebitic syndrome are limited, but
      include compression stockings and intermittent compressive therapy with an
      extremity pump for severe cases. To date, quality of life after DVT has received
      little attention in the literature. The recent development of the VEINES-QOL
      questionnaire, a validated venous-disease-specific measure of quality of life,
      should encourage researchers to include quality of life as a routine outcome
      measure after DVT. There is no criterion standard for the diagnosis of
      postphlebitic syndrome, but a validated clinical scoring system does exist. More
      research on postphlebitic syndrome is needed to enable us to provide DVT patients
      with comprehensive, evidence-based information regarding their long-term
      prognosis, to help quantify the prevalence and health care burden of
      postphlebitic syndrome, and by identifying predictors of poor outcome, to develop
      new preventive strategies in patients at risk of developing this condition.

PMID- 10886479
TI  - Decision analytic modeling and NSAID gastropathy could we be more sensitive?

PMID- 10886480
TI  - Procedural competence of internal medicine residents: time to address the gap.

PMID- 10886481
TI  - Overcoming barriers to preventive care.

PMID- 10886482
TI  - ICU use and mortality in the elderly.

PMID- 10886483
TI  - Telemedicine: barriers and opportunities in the 21st century.
AB  - This paper aims to examine how health telematics will develop in the first 10
      years of the new millennium and, in particular, to assess what operational,
      ethical and legal barriers may lie in the way of this development. A description
      of the key principles and concepts involved in telemedicine and a short
      historical overview of telemedicine's evolution over the past century are
      followed by consideration of why empirical research into 'info-ethics' and other
      deontological and legal issues relating to telemedicine is being necessarily
      catalysed by, amongst others, the European Commission. Four evolving health
      telematics applications are examined in some detail: electronic health records;
      the transmission of visual media in disciplines such as teleradiology,
      teledermatology, telepathology and teleophthalmology; telesurgery and robotics
      and the use of call centres and decision-support software. These are discussed in
      the light of their moral, ethical and cultural implications for clinicians,
      patients and society at large. The author argues that telemedicine presents
      unique opportunities for both patients and clinicians where it is implemented in
      direct response to clear clinical needs, but warns against excessive reliance
      upon technology to the detriment of traditional clinician-patient relationships
      and against complacency regarding the risks and responsibilities - many of which
      are as yet unknown - that distant medical intervention, consultation and
      diagnosis carry.

PMID- 10886484
TI  - Independent importance of psychosocial factors for prognosis after myocardial
      infarction.
AB  - AIMS: As a primary aim it was tested whether the 10-year prognosis after a
      myocardial infarction is related to psychological stress, lack of social support,
      anxiety, and/or depressive tendency. A secondary aim was to analyse the
      prognostic importance of a series of other psychosocial factors as well as
      interactions. METHODS: Non-selected patients aged below 65 years with a first
      infarction (230 men and 45 women) were followed for 10 years with 100% assessment
      of morbidity and cause-specific mortality. Baseline somatic and psychosocial
      variables were collected with the aid of standard, validated questionnaires.
      RESULTS: In multivariate analysis, factors increasing risk for coronary mortality
      included female sex (hazard ratio, +/- 95% confidence interval) 2.47 (1.06,
      5.71), signs of left ventricular failure 3.93 (1.87, 8.26), ventricular
      dysrhythmia 3 months after the infarction 5.45 (2.21, 13. 42), high depression
      scores 3.16 (1.38, 7.25) and lack of social support 2.75 (1.29, 5.89). All-cause
      mortality was significantly related to left ventricular failure, ventricular
      dysrhythmias, and high depression scores with borderline significance for female
      sex and social support. Prognosis was affected during the entire follow-up
      period. It was not significantly associated with age, marital status, education,
      extra work, mental strain at work or in the marriage, anxiety, dissatisfaction
      with family life, problems with children, dissatisfaction with the financial
      situation, life events, anger-in, irritability, type A behaviour, or health locus
      of control. Incidence of nonfatal infarction was not associated with any of the
      baseline variables. CONCLUSION: In addition to known somatic predictors of
      prognosis after a myocardial infarction, prognosis is strongly influenced by
      depression and lack of social support, but not to a series of other psychosocial
      factors. It is recommended to use self-reporting scales to detect prognostically
      important psychosocial problems.

PMID- 10886485
TI  - Early postoperative growth hormone levels: high predictive value for long-term
      outcome after surgery for acromegaly.
AB  - OBJECTIVES: To explore the prognostic value of early - within 1 week -
      postoperative growth hormone (GH) measurements with regard to outcome after
      surgery for acromegaly in a short- and a long-term perspective. DESIGN:
      Retrospective study of patients operated on between 1987 and 1998, including
      follow-up for up to 60 months. SETTING: University hospital. SUBJECTS: Sixty
      eight patients with acromegaly. INTERVENTION: Pituitary surgery aiming at
      adenomectomy with preservation of pituitary function. MAIN OUTCOME MEASURES: The
      effect of the operation was evaluated after 3 months, mostly by means of an oral
      glucose load or by insulin-like growth factor 1 (IGF-1). The specificity,
      sensitivity and the predictive values of an early postoperative mean GH
      concentration </= 4.8 mU L-1, as well as of the GH response to thyrotropin
      releasing hormone (TRH) 3 months after surgery, were calculated with regard to
      outcome of the operation in both 3-month and long-term perspectives. RESULTS:
      Fifty patients (73.5%) showed a satisfactory effect at the evaluation 3 months
      postoperatively; 45 of these were followed between 12 and 60 months. Relapse was
      registered in five cases: 12, 12, 24, 24 and 48 months after surgery. In the long
      term perspective, the predictive value of an early mean GH </= 4.8 mU L-1 was
      93.6% with regard to a satisfactory effect of surgery, compared with 90.2% for a
      normalized somatomedin C (SmC)/IGF-1 and 90.0% for an absent GH response after
      TRH. An early mean GH > 4.8 mU L-1 had a 77.8% predictive value for persistent or
      recurrent disease, compared with 85.7% for persistently increased SmC/IGF-1 and
      68.8% for an abnormal GH release after TRH 3 months after surgery. In the short
      term perspective, the specificity and the predictive value of an early GH </= 4.8
      mU L-1 were 77.3 and 97.1%, respectively. Early GH > 4.8 mU L-1 had a 94.4%
      sensitivity but a predicative value of only 63.0% for an unsatisfactory effect.
      CONCLUSION: Measurement of GH within 1 week after surgery is highly predictive
      for outcome of surgery for acromegaly. Specifically, an early mean GH </= 4.8 mU
      L-1 is as predictive for a satisfactory effect of treatment as a normalized IGF-1
      3 months after surgery. Early postoperative GH values > 4.8 mU L-1 have a high
      sensitivity for persistent or recurrent disease in both the short- and long-term
      perspectives, but lower predictive value. The usefulness of the TRH test can be
      questioned.

PMID- 10886486
TI  - The Q/E27 polymorphism in the beta2-adrenoceptor gene is associated with
      increased body weight and dyslipoproteinaemia involving triglyceride-rich
      lipoproteins.
AB  - OBJECTIVES: To investigate whether a substitution of glutamine by glutamic acid
      at amino acid position 27 (Q/E27) and an arginine to glycine transition at amino
      acid 16 (R/G16) in the beta2-adrenoceptor gene are associated with lipid and
      lipoprotein disturbances and/or increased body weight in men. DESIGN: Population
      based study. SETTING: Department of medicine at a university hospital. SUBJECTS:
      A total of 180 healthy men, aged 30-45 years, were recruited at random from a
      register containing all permanent residents in Stockholm County (response rate of
      70%). MAIN OUTCOME MEASURES: Frequency of beta2-adrenoceptor genotypes and
      alleles in relation to plasma lipid and lipoprotein levels and body mass index.
      RESULTS: Individuals carrying the E27 allele and/or the G16 allele had
      significantly higher body mass index (BMI). Furthermore, carriers of the E27
      allele had significantly higher plasma concentrations of cholesterol,
      triglycerides, VLDL cholesterol and VLDL triglycerides than did subjects
      homozygous for the Q allele. CONCLUSION: The E27 allele of the beta2-adrenoceptor
      gene is associated with slightly to moderately elevated BMI and
      dyslipoproteinaemia involving triglyceride-rich lipoproteins in healthy younger
      and middle-aged men.

PMID- 10886487
TI  - Effects of on-demand beta2-agonist inhalation in moderate-to-severe asthma. A
      randomized controlled trial.
AB  - BACKGROUND: The appropriate use of short-acting beta2-agonist inhalation in
      asthma has been the subject of controversy in recent years. Limited information
      is available for the group of moderate to severe asthmatics with high intake of
      bronchodilator inhalants and continuous anti-inflammatory protection. OBJECTIVE:
      To investigate the effects of beta2-agonist reduction in marked asthma treated
      with multiple asthma medications. DESIGN: Randomized, controlled single-blind,
      cross-over trial. SETTING: Outpatient clinic at a university medical centre.
      SUBJECTS: A total of 80 adult patients with moderate-to-severe asthma.
      INTERVENTIONS: In a 1-year study patients were assigned to on-demand vs. regular
      beta2-agonist inhalation treatment. MAIN OUTCOME MEASURES: Asthmatic episodes
      (primary outcome), symptoms, peak expiratory flow rates (PEF) and drug use were
      recorded daily. Bronchodilator and airway responsiveness, lung function indices
      and quality of life were assessed during five clinic visits. Also, practicability
      of beta2-agonist tapering in multimedicated asthmatics was analysed. RESULTS:
      More than 80% of moderate-to-severe asthmatics were able to reduce their beta2
      agonist intake by >/=50%. Puffs per day of active therapy decreased from 7.9 in
      regular to 3.3 in on-demand treated patients (P = 0.0001). The type of beta2
      agonist used (salbutamol/fenoterol) had no significant impact on the study
      findings. Almost all parameters of control of asthma improved during the on
      demand treatment period. CONCLUSION: On-demand inhalation of short-acting beta2
      agonists in moderate-to-severe asthma is safe, and even in severe asthma a
      reduction from regular to on-demand beta2-agonist inhalation is possible, with
      improved asthma control.

PMID- 10886488
TI  - Desmopressin and hexarelin tests in alcohol-induced pseudo-Cushing's syndrome.
AB  - BACKGROUND: A challenge in clinical endocrinology is the distinction between
      Cushing's disease (Cushing's syndrome dependent by adrenocorticotrophic hormone
      (ACTH)-secreting tumours of pituitary origin) and alcohol-dependent pseudo
      Cushing's syndrome. Patients with Cushing's disease are known to have high
      ACTH/cortisol responses to desmopressin (DDAVP, a vasopressin analogue) and to
      hexarelin (HEX, a synthetic GH-releasing peptide). OBJECTIVE: To compare the
      ACTH/cortisol responses to desmopressin and to hexarelin of subjects with alcohol
      pseudo-Cushing's syndrome with those obtained in patients with Cushing's disease
      and in normal controls. DESIGN: Randomized, single-blind study. SETTING:
      University medical centre. SUBJECTS: Eight alcoholics with pseudo-Cushing's
      syndrome, six patients with Cushing's disease and nine age-matched normal
      controls. INTERVENTION: Three tests at weekly intervals. The dexamethasone (1 mg)
      suppression test (DST) was carried out first. The desmopressin (10 microg
      intravenously at 09:00 h) test and hexarelin (2 microgram kg-1 intravenously at
      09:00 h) test were carried out in random order. MEASUREMENTS: Plasma ACTH and
      cortisol levels. RESULTS: The basal plasma levels of ACTH and cortisol were
      significantly lower in normal subjects than in patients with Cushing's disease
      and in alcoholic subjects; these latter groups showed similar basal hormonal
      values. All normal controls, two patients with Cushing's disease and two
      alcoholics showed suppression of plasma cortisol levels (<5 microgram dL-1) after
      dexamethasone administration. Both desmopressin and hexarelin induced striking
      ACTH/cortisol responses in patients with Cushing's disease, whereas hexarelin,
      but not desmopressin, slightly increased ACTH/cortisol secretion in the normal
      controls. Neither desmopressin nor hexarelin administration induced any
      significant change in ACTH/cortisol secretion in alcoholics. CONCLUSIONS: These
      data suggest that either the hexarelin or desmopressin test can be used to
      differentiate patients with Cushing's disease from subjects with alcohol
      dependent pseudo-Cushing's syndrome.

PMID- 10886489
TI  - Ehrlichiosis associated vasculitis.
AB  - OBJECTIVE: To test the hypothesis that some cases of primary vasculitis are
      caused by ehrlichiosis. DESIGN: A retrospective case study and serological
      analysis of stored sera. SETTING: University hospital. SUBJECTS: Fifty-five
      patients discharged with any type of vasculitis over a 6-year period. MAIN
      OUTCOME MEASURES: Serology for human monocytic ehrlichiosis, and the human
      granulocytic ehrlichiosis agent, and polymerase chain reaction (PCR) analysis of
      biopsy specimens. RESULTS: Three patients (5.5%) had titres of 1 : 128 or higher
      against E. chaffeensis; none was positive for the human granulocytic ehrlichiosis
      agent. Skin biopsies of these patients showed lesions compatible with
      polyarteritis nodosa, allergic purpura and unspecified vasculitis. PCR analysis
      of the biopsies was unrevealing. CONCLUSIONS: Infection with human monocytic
      ehrlichiosis may underlie some forms of vasculitis. If confirmed, these findings
      may help identify patients with vasculitis who would benefit from antibiotic
      treatment.

PMID- 10886490
TI  - Carotid atherosclerosis, vascular risk profile and mortality in a population
      based sample of functionally healthy elderly subjects: the Berlin ageing study.
AB  - OBJECTIVES: Studies on extracranial carotid atherosclerosis have predominately
      been undertaken on middle-aged subjects. This study examines the prevalence of
      extracranial carotid atherosclerosis, its relation to vascular risk factors and
      its significance for survival in elderly subjects. DESIGN: Population-based cross
      sectional survey. Non-modifiable vascular risk factors examined were family
      history of atherosclerotic disease, sex and apolipoprotein E (apoE) genotype.
      Potentially modifiable risk factors assessed were smoking, fibrinogen, fasting
      lipids, body mass index, hypertension and diabetes. SETTING AND SUBJECTS: Two
      hundred and twenty-five functionally healthy volunteers of the Berlin Ageing
      Study, aged 70-100. MAIN OUTCOME MEASURES: Presence of carotid stenosis and
      plaque ascertained by ultrasound imaging; 5-year mortality. RESULTS: At least one
      plaque was found in 144 (64%) of the volunteers; 34 (15%) had a stenosis over
      50%; and nine (4%) had a stenosis over 75%. Total cholesterol > 6.5 mmol L-1, LDL
      cholesterol > 4.6 mmol L-1 and total cholesterol/HDL cholesterol ratio > 5 were
      significantly associated with presence of plaque in 70- to 80-year-old subjects,
      as was diabetes in subjects over 80 years. Log-linear analyses showed significant
      three-way interactions for high LDL cholesterol and diabetes with plaques and
      age. Family history, sex, apoE genotype, smoking and fibrinogen were not related
      to presence of plaque in the study population. Cox regression analysis revealed
      increased 5-year mortality rates for subjects with plaques (OR = 2. 88; 95% CI =
      1.30-6.35), whereas the vascular risk profile was not associated with mortality.
      CONCLUSIONS: In a population-based sample of functionally healthy elderly
      subjects, the significance of the vascular risk profile seemed to be diminished.
      It had no impact on survival and only modifiable risk factors showed an age
      dependent association with carotid disease.

PMID- 10886491
TI  - Genetic background of Lewis negative blood group phenotype and its association
      with atherosclerotic disease in the NHLBI family heart study.
AB  - OBJECTIVES: To examine the prevalence of four mutations, T59G, T1067A, T202C and
      C314T, of the human alpha(1,3/1,4) fucosyltransferase 3 (FUT 3) gene amongst
      persons with Lewis negative and those with Lewis positive blood group phenotype.
      An additional objective was to explore the hypothesis that these mutations are
      associated with coronary heart disease and inflammatory reaction. DESIGN: A
      population-based cross-sectional study. SETTING: Analysis of samples and data
      from the National Heart Lung and Blood Institute Family Heart Study. SUBJECTS:
      All Lewis (a-b-) participants (n = 136) and a sample of Lewis positive
      participants (n = 136) of the Family Heart Study; all were of Caucasian
      ethnicity. MAIN OUTCOME MEASURES: The prevalence of examined mutations by Lewis
      phenotype. RESULTS: The examined mutations were common and strongly associated
      with the Lewis (a-b-) phenotype. Accordingly, 90-95% of Lewis (a-b-) individuals
      amongst Caucasians can be identified by screening for these four mutations.
      Exploratory analyses suggested that with the exception of T59G, all examined
      mutations were positively associated with prevalent coronary heart disease,
      although not statistically significantly, perhaps due to the small number of
      prevalent coronary heart disease cases. C-reactive protein tended to be higher
      amongst persons with a TC or CC genotype at position 202 (3.07 +/- 0.41 vs. 2.08
      +/- 0.32 mg L-1, P = 0.06). CONCLUSIONS: Four specific mutations of
      fucosyltransferase 3 gene are responsible for the vast majority of Lewis (a-b-)
      phenotypes in Caucasians. These mutations are common in the population at large
      and may be associated with increased risk of coronary heart disease. Further
      studies using larger samples are warranted.

PMID- 10886492
TI  - N-terminal atrial natriuretic peptide and left ventricular geometry and function
      in a population sample of elderly males.
AB  - OBJECTIVES: To investigate the relationships between N-terminal atrial
      natriuretic peptide (N-ANP) and left ventricular geometry and function. DESIGN: A
      cross-sectional study of a population-based cohort. SETTING: Follow-up of a
      health survey in Uppsala county, Sweden. SUBJECTS: Two hundred and five men aged
      70. MAIN OUTCOME MEASURES: A Delfia sandwich immunoassay was used to measure the
      plasma levels of N-ANP. M-mode and Doppler echocardiographic examinations were
      used to measure left ventricular dimensions, mass, geometry and systolic function
      and to classify the subjects into four groups (normal geometry, concentric
      remodelling, concentric hypertrophy or eccentric hypertrophy). Left ventricular
      systolic dysfunction was defined as a left ventricular ejection fraction </=
      0.40. RESULTS: Plasma levels of N-ANP were significantly increased in subjects
      with left ventricular dysfunction compared to healthy subjects (702 +/- 486, n =
      14 vs. 277 +/- 201 pmol L-1, n = 118, P < 0.0001), but there was a great overlap
      between the groups. N-ANP differed significantly between the four different left
      ventricular geometric groups (P = 0.02) with the highest N-ANP levels in the
      subjects with left ventricular eccentric hypertrophy (n = 40). However, N-ANP
      levels were no longer significantly associated with left ventricular geometry
      when taking the ejection fraction into account. CONCLUSIONS: This study showed
      that N-ANP levels were significantly elevated in subjects with left ventricular
      dysfunction, as well as in subjects with left ventricular hypertrophy. However,
      the increase in N-ANP seen in the eccentric hypertrophy group was mainly due to a
      decreased ejection fraction.

PMID- 10886493
TI  - Resting energy expenditure, growth hormone indices, body composition and adipose
      tissue distribution in premenopausal women.
AB  - OBJECTIVES: A significant growth hormone (GH) contribution to interindividual
      variance in energy expenditure (REE) in women can be hypothesized. The present
      study examines the independent association between physiological levels of GH
      function indices and REE. SETTING: All subjects were hospitalized in the
      Institute of Internal Medicine of the University of Verona. SUBJECTS: Twenty-four
      premenopausal overweight (BMI = 28-55 kg m-2) women aged 18-49 years.
      INTERVENTIONS: REE was estimated by indirect calorimetry and body composition and
      fat distribution by single slice computed tomography method. GH activity and GH
      status were determined by measuring serum levels of insulin-like growth factor I
      (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3). RESULTS: GH
      indices did not show any significant correlation with REE. The relation between
      GH indices and REE was also examined by multiple regression analysis to account
      for possible confounders such as body composition, adipose tissue distribution
      and age. When body composition was considered, body fat and fat-free mass were
      the only significant predictors of REE (R2 = 0.699, P = 0.0001). The
      contributions of GH indices were not significant. CONCLUSIONS: Our findings do
      not support the hypothesis that GH in physiological conditions could be an
      independent determinant of REE in women with obesity.

PMID- 10886494
TI  - Impaired leukotriene C4 generation in granulocytes from protein-energy
      malnourished chronically ill elderly.
AB  - OBJECTIVE: The dysregulation of the immune and inflammatory systems observed in
      protein-energy malnutrition (PEM) may be partly due to perturbation of essential
      fatty acid metabolism. In this study, we assessed the calcium ionophore A23187
      induced generation of the arachidonate metabolites leukotriene B4 (LTB4) and
      leukotriene C4 (LTC4) in isolated granulocyte suspensions. DESIGN: Case-control
      study. SETTING: A university-affiliated acute care hospital in urban Stockholm.
      SUBJECTS: Fourteen severely malnourished elderly subjects with stable non
      malignant disorders (age 74 +/- 1 years, mean +/- SEM) and 12 healthy age-matched
      controls were examined. MAIN OUTCOME MEASURES: Leukotrienes were analysed by high
      performance liquid chromatography. Body mass index (BMI, kg m-2) and delayed
      cutaneous hypersensitivity (DCH) reaction were determined. RESULTS: BMI was 16. 5
      +/- 0.5 and 26.2 +/- 0.9 kg m-2 (mean +/- SE) in the malnourished group and
      controls (P < 0.001), respectively. DCH was 8.5 mm (median) in patients and 29.5
      mm in controls (P < 0.001). LTC4 generation in granulocytes from PEM patients was
      half of that of controls (9.1 +/- 2.0 vs. 17.8 +/- 5.2 pmol mL-1, P < 0.05) when
      cells were stimulated with 0.2 micromol L-1 of A23187, and 13.7 +/- 2.5 and 27.2
      +/- 7.5 pmol mL-1, respectively (NS), upon stimulation with 1.0 micromol L-1 of
      A23187. LTB4 production in PEM patients and controls did not differ at any of the
      two calcium ionophore concentrations. LTC4 production correlated with BMI (r =
      0.41, P < 0.05), but there was no significant correlation between DCH and LTB4 or
      LTC4 production. CONCLUSION: Protein-energy malnutrition is accompanied by
      perturbation of leukotriene synthesis, which may be one factor underlying the
      dysregulation of inflammatory responses in the depleted patient.

PMID- 10886495
TI  - Acute respiratory failure associated with catastrophic antiphospholipid syndrome.
AB  - We present a case of multiple organ dysfunction syndrome with acute respiratory
      failure due to alveolar haemorrhage associated with antiphospholipid antibodies
      in a 42-year-old woman with a medical history of antinuclear antibody-negative
      systemic lupus erythematosus and antiphospholipid syndrome. Severe respiratory
      failure, circulatory shock and acute renal failure necessitated artificial
      ventilation, inotropic and vasopressor therapy, and continuous venovenous
      haemofiltration. A tentative diagnosis of haemorrhagic lupus pneumonitis or
      pulmonary manifestation of antiphospholipid syndrome was made. Lupus
      anticoagulant, IgG anticardiolipin and anti-beta2-glycoprotein I antibodies were
      positive. High-dose glucocorticoid, anticoagulation with heparin, plasmapheresis
      and cyclophosphamide improved her clinical condition. Despite this, the patient
      died several days later of spontaneous intracranial haemorrhage. This case
      illustrates the uncommon manifestation of acute respiratory failure associated
      with antiphospholipid syndrome.

PMID- 10886496
TI  - Chronic systemic capillary leak syndrome. Report of a case and review of the
      literature.
AB  - Systemic capillary leak syndrome (SCLS) is a rare condition characterized by
      recurrent episodes of generalized oedema and severe hypotension, associated with
      paraproteinaemia. In addition to the acute form, a few cases of chronic SCLS have
      been reported. We describe a 64-year-old woman who was hospitalized because of a
      6-month history of progressive generalized oedema with pericardial and pleural
      effusions, associated with a serum paraprotein. Clinical and laboratory findings
      were consistent with a chronic form of SCLS. Treatment with prednisone,
      furosemide and theophylline was started, which led to a gradual improvement in 2
      weeks and a persistent remission after 9 months. This report indicates that SCLS
      may occur in a chronic form, which seems to be responsive to a therapeutic
      regimen with prednisone, furosemide, and theophylline.

PMID- 10886497
TI  - Chronic fatigue syndrome: a form of Addison's disease.

PMID- 10886498
TI  - LETTERS TO THE EDITOR: Reply.

PMID- 10886499
TI  - In this issue

PMID- 10886500
TI  - Delayed wound healing in immunodeficient TGF-beta 1 knockout mice.
AB  - Previous studies showed that full-thickness wounds in transforming growth factor
      beta1-deficient mice initially heal normally. Unfortunately, transforming growth
      factor-beta1 deficiency leads to a multifocal inflammatory disease affecting most
      organs of the body, which ultimately interferes with later stages of wound
      healing in these mice. As this inflammatory disease is eliminated in transforming
      growth factor-beta1-deficient mice lacking T and B cells (Tgfb1-/- Scid-/- mice),
      we hypothesized that wound repair in the latter would proceed normally, even at
      later stages of healing. Unexpectedly, Tgfb1-/- Scid-/- mice demonstrate a major
      delay of approximately 1 wk in each of the major phases of wound healing:
      inflammation, proliferation, and maturation. Immuno- deficient Scid-/- mice that
      have the wild-type Tgfb1 allele do not experience this delay in wound healing.
      One interpretation of these findings is that lymphocytes and transforming growth
      factor-beta1 affect compensatory pathways in wound healing. An alternative
      interpretation is that the delayed expression of Tgfb2 and Tgfb3 that occurs in
      the absence of transforming growth factor-beta1 results in the delayed wound
      healing, suggesting that transforming growth factor-beta2 and/or transforming
      growth factor-beta3 play important parts in wound healing.

PMID- 10886501
TI  - Expression and proteolysis of vascular endothelial growth factor is increased in
      chronic wounds.
AB  - Degradation of angiogenic mediators might be an underlying cause of chronic
      wounds. To test this hypothesis, we evaluated the expression and integrity of
      vascular endothelial growth factor, a potent angiogenic mediator, and its
      receptors, Flt-1 and KDR, in chronic venous leg ulcerations. Immunohisto-
      chemical, in situ hybridization, and semiquantitative reverse transcriptase
      polymerase chain reaction analyses all indicate that expression of vascular
      endothelial growth factor is elevated in ulcerative tissue, with vascular
      endothelial growth factor mRNA being especially pronounced in the hyperplastic
      epithelium of the wound margin. Flt-1 and KDR protein and mRNA were detected in
      the papillary vessels in close vicinity to the lesional epithelium of chronic
      wounds. Although increased expression of vascular endothelial growth factor
      protein was detected in the epidermis, the intensity of this staining was weak
      compared with the epidermal staining in psoriatic lesions and compared with the
      strong vascular endothelial growth factor mRNA signal in chronic wounds and
      psoriasis. To analyze whether this apparent decrease in immunoreactivity could be
      the result of degradation of vascular endothelial growth factor by proteolytic
      activities from the wound environment, we examined the stability of recombinant
      vascular endothelial growth factor in wound fluid from chronic leg ulcers. As
      demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis,
      incubation of rVEGF165 with chronic, but not acute, wound fluid resulted in rapid
      proteolytic degradation of rVEGF165. Protease inhibitor studies indicate that
      serine proteases, such as plasmin, are involved in this degradation. Together,
      our data show that, although vascular endothelial growth factor expression is
      elevated in chronic wounds, increased proteolytic activity in this environment
      results in its degradation, which may contribute to an impaired wound healing
      response.

PMID- 10886502
TI  - Neonatal murine epidermal cells express a functional multidrug-resistant pump.
AB  - Phospho-glycoproteins are members of the ABC transporter family encoded by the
      multidrug-resistant genes. These proteins are highly expressed in many tumor
      cells derived from patients undergoing treatment with anti-cancer drugs. Phospho
      glycoproteins are large 12 transmembrane spanning molecules of 170 kDa, involved
      in adenosine-5'-triphosphate-dependent efflux of molecules out of the cell, known
      currently as multidrug-resistant pumps. Expression analysis of phospho
      glycoproteins in mice and humans indicates widespread distribution in a number of
      organs, such as brain and testis. We have analyzed skin, and more particularly
      keratinocytes, to determine whether they express phospho-glycoproteins and
      express the multidrug-resistant phenotype. Immunofluorescent staining of skin
      showed that keratinocytes located in the basal layer of the epidermis
      preferentially expressed phospho-glycoproteins, as did the outer root sheath
      cells of hair follicles. Phospho-glycoprotein expression on the basal cells was
      restricted to the cell surface. Polymerase chain reaction analysis of first
      strand cDNA from keratinocytes identified the phospho-glycoproteins to be mdr1b.
      Using beta1 integrin expression and density gradient centrifugation we were able
      to enrich and identify the basal cell compartment by flow cytometric analysis and
      assay this subset of cells for phospho-glycoprotein activity. Basal cells loaded
      with rhodamine 123, a substrate for multidrug-resistant pumps, effluxed the
      molecule from the cells in a time-dependent manner. This study shows that basal
      layer keratinocytes express functional phospho-glycoproteins. We speculate that
      phospho-glycoproteins may play a role in regulating the level of environmental
      toxins and differentiation factors, as has been suggested for other progenitor
      cell compartments.

PMID- 10886503
TI  - Differential roles of insulin receptor and insulin-like growth factor-1 receptor
      in differentiation of murine skin keratinocytes.
AB  - The insulin receptor and the insulin-like growth factor-1 receptor are widely
      expressed tyrosine kinases that mediate insulin and insulin-like growth factor-1
      signaling. Both receptors are expressed in many cells in which insulin
      stimulation does not result in an increase in glucose transport, and the distinct
      role of the insulin receptor in these tissues, is not known. We have studied the
      regulation of insulin receptor and insulin-like growth factor-1 receptor in the
      differentiation of cultured murine keratinocytes. Both receptors are expressed in
      skin keratinocytes and their expression was unchanged in all stages of calcium
      induced differentiation. Insulin binding to skin keratinocytes, however,
      increased during calcium-induced differentiation, whereas insulin-like growth
      factor-1 binding decreased. Ligand-induced autophosphorylation was also changed
      during differentiation. In proliferating keratinocytes both receptors became
      phosphorylated upon ligand binding, insulin-like growth factor-1 receptor to a
      greater extent. Terminal differentiation resulted in a decrease in insulin
      receptor autophosphorylation, whereas insulin-like growth factor-1 receptor
      autophosphorylation was abolished. There was no change in the cellular
      localization of the proteins, their intrinsic activity, or their internal
      structure. Finally, due to the change in the receptor's activity during
      keratinocyte differentiation, the role of insulin and insulin-like growth factor
      1 in the differentiation process was examined. The expected increase in the
      expression of keratins 1 and 10 during calcium-induced differentiation was
      facilitated in the presence of insulin, whereas this induction was inhibited in
      the presence of insulin-like growth factor-1. In conclusion, these results
      demonstrate that insulin and insulin-like growth factor-1 signaling pathways are
      differentially involved in skin differentiation, suggesting that abnormal insulin
      signaling, as occurs in diabetes, may lead to skin pathology.

PMID- 10886504
TI  - Ultraviolet-A-induced transactivation of the vascular endothelial growth factor
      gene in HaCaT keratinocytes is conveyed by activator protein-2 transcription
      factor.
AB  - Ultraviolet-A radiation represents a significant proportion of the ultraviolet
      solar spectrum that was recently shown to affect gene expression of epidermal
      keratinocytes by molecular mechanisms distinct from ultraviolet-B radiation. As
      ultraviolet-A either alone or in combination with ultraviolet-B may contribute to
      photocarcinogenesis, we aimed to explore the biologic effects of ultraviolet-A
      radiation on vascular endothelial growth factor gene expression by the
      immortalized keratinocyte cell line HaCaT. As keratinocyte-derived vascular
      endothelial growth factor not only provides the major cutaneous angiogenic
      activity but may also augment the malignant phenotype of tumor cells, we studied
      the molecular mechanisms of ultraviolet-A-induced vascular endothelial growth
      factor expression in HaCaT cells, serving as a transformed preneoplastic
      epithelial cell line. Whereas ultraviolet-B-mediated vascular endothelial growth
      factor expression has been previously indicated to be conveyed by indirect
      mechanisms, ultraviolet-A rapidly induced vascular endothelial growth factor mRNA
      expression in a fashion comparable to that seen with the transforming growth
      factor alpha, representing a direct and potent activator of vascular endothelial
      growth factor gene transcription. Ultraviolet-A was found to readily induce
      vascular endothelial growth factor promoter-based reporter gene constructs
      through a consensus element for activator protein-2 transcription factor. The
      critical role of activator protein-2 was substantiated by demonstration of
      ultraviolet-A-induced activator-protein-2-dependent nuclear DNA binding activity
      to this site, and by inhibition of ultraviolet-A-mediated vascular endothelial
      growth factor gene transcription through insertion of a critical mutation within
      the activator protein-2 sequence. Together, our data further elucidate
      photobiologic aspects of ultraviolet-A-induced gene expression by characterizing
      mechanisms of vascular endothelial growth factor upregulation at the molecular
      level. In addition, our experiments support the concept of a more general
      importance of activator protein-2 in ultra- violet-A-mediated responses by
      keratinocytes or keratinocyte-derived cell lines.

PMID- 10886505
TI  - Protection by ultraviolet A and B sunscreens against in situ dipyrimidine
      photolesions in human epidermis is comparable to protection against sunburn.
AB  - Sunscreens prevent sunburn and may also prevent skin cancer by protecting from
      ultraviolet-induced DNA damage. We assessed the ability of two sunscreens, with
      different spectral profiles, to inhibit DNA photodamage in human epidermis in
      situ. One formulation contained the established ultraviolet B filter octyl
      methoxycinnamate, whereas the other contained terephthalylidene dicamphor
      sulfonic acid, a new ultraviolet A filter. Both formulations had sun protection
      factors of 4 when assessed with solar simulating radiation in volunteers of skin
      type I/II. We tested the hypothesis that sun protection factors would indicate
      the level of protection against DNA photodamage. Thus, we exposed sunscreen
      treated sites to four times the minimal erythema dose of solar simulating
      radiation, whereas vehicle and control sites were exposed to one minimal erythema
      dose. We used monoclonal antibodies against thymine dimers and 6-4 photoproducts
      and image analysis to quantify DNA damage in skin sections. A dose of four times
      the minimal erythema dose, with either sunscreen, resulted in comparable levels
      of thymine dimers and 6-4 photoproducts to one minimal erythema dose +/- vehicle,
      providing evidence that the DNA protection factor is comparable to the sun
      protection factor. The lack of difference between the sunscreens indicates
      similar action spectra for erythema and DNA photodamage and that erythema is a
      clinical surrogate for DNA photodamage that may lead to skin cancer.

PMID- 10886506
TI  - Characterization of a transcription factor binding site, specifically activating
      MIA transcription in melanoma.
AB  - We have previously isolated the protein MIA, which is secreted from melanoma
      cells, and identified highly restricted expression patterns in melanocytic
      tumors. Preliminary studies of the human MIA gene provided evidence that the
      promoter is specifically activated in melanoma cells but is silent in
      nonmelanocytic cells and benign melanocytes. In this study we aimed to identify
      cis-regulatory promoter elements that mediate promoter activation during
      malignant transformation of melanocytes. We therefore subcloned 1.4 kb of the
      murine MIA promoter and a series of 5' deletion constructs into a luciferase
      reporter plasmid and identified the most active cis-regulatory element between
      nucleic acids -230 and -130. Cloning oligomeric fragments of this promoter region
      in front of a minimal TK promoter revealed a 30 bp enhancer element mediating
      expression of the reporter gene in melanoma cells but not in melanocytes or
      nonmelanocytic cells. Gel mobility shift assays and southwestern blots led to the
      identification of specific DNA-protein complexes in melanoma cells. Fine
      mutational analysis of the cis-regulatory promoter element showed that two
      critical nucleic acid residues are essential for both transcriptional activity
      and formation of the band shift complexes. By an initial small-scale affinity
      purification we were able to isolate a protein approximately 32 kDa in size from
      melanoma cells, which we refer to as MATF ("melanoma-associated transcription
      factor"). Our study identified for the first time MATF, a transcription factor
      that is upregulated or activated during malignant transformation of melanocytes.

PMID- 10886507
TI  - Human melanocytes and melanomas express novel mRNA isoforms of the tyrosinase
      related protein-2/DOPAchrome tautomerase gene: molecular and functional
      characterization.
AB  - We previously reported that a melanoma antigen, recognized by tumor-specific
      cytotoxic T lymphocytes, was encoded by intron sequences retained in a partially
      spliced transcript of the tyrosinase-related protein-2/DOPAchrome tautomerase
      gene. At difference with the mRNA encoding tyrosinase-related protein-2, this
      anomalous transcript was not expressed in melanocytes. This study examined
      whether neoplastic and/or normal cells of the melanocytic lineage could express
      additional forms of tyrosinase-related protein-2 mRNA. Screening of a melanoma
      derived cDNA library with a tyrosinase-related protein-2 probe allowed
      identification of two novel isoforms. The first, tyrosinase-related protein-2
      long tail, corresponds to the dominant transcript detected on melanomas and
      melanocytes by northern blot analysis. Tyrosinase-related protein-2-long tail is
      identical to the tyrosinase-related protein-2-encoding published cDNA sequence
      except for an extended 3'-untranslated region and is originated by alternative
      polyadenylation. This novel 3'-untranslated region contains an alternatively
      spliced, tyrosinase-related protein-2 last exon in the second isoform (tyrosinase
      related protein-2-8b). The protein encoded by tyrosinase-related protein-2-8b is
      identical to tyrosinase-related protein-2 in its first 460 amino acids but
      possesses a different carboxyl-terminus devoid of transmembrane domain.
      Tyrosinase-related protein-2-long tail exhibited DOPA-chrome tautomerase
      activity, when transiently transfected into COS-7 cells. On the contrary, no
      detectable activity was exhibited by tyrosinase-related protein-2-8b. Reverse
      transcription-polymerase chain reaction analysis indicated that tyrosinase
      related protein-2-long tail and tyrosinase-related protein-2-8b are expressed by
      tyrosinase-related protein-2-positive melanomas and normal melanocytes. Moreover
      all cell lines positive for tyrosinase-related protein-2 isoforms expressed
      tyrosinase and, all but one, tyrosinase-related protein-1. These data show that
      the human tyrosinase-related protein-2/DOPAchrome tautomerase gene can yield
      different isoforms by alternative poly(A) site usage or by alternative splicing.
      The pattern of expression of these isoforms suggest that they might play a part
      in the normal pathway of melanin biosynthesis.

PMID- 10886508
TI  - Tumor antigen presentation by dermal antigen-presenting cells.
AB  - Several phenotypes of antigen-presenting cells are present in the dermis, where
      they presumably function to present encountered antigens for immune responses.
      This study examined the ability of dermal antigen-presenting cells to present
      tumor-associated antigens for the induction of in vivo antitumor immunity. Total
      murine dermal cells were exposed either to medium alone or to medium containing
      tumor-associated antigens from S1509a tumor cells. Subsequently, dermal cells
      were injected subcutaneously at weekly intervals into naive mice for a total of
      three immunizations. One week following the final immunization, mice were
      challenged with living tumor cells. In these experiments, dermal cells pulsed
      with tumor-associated antigens induced protective immunity to tumor growth.
      Dermal cells exposed to tumor-associated antigens were also able to elicit
      delayed-type hypersensitivity after footpad injection into mice previously
      immunized against S1509a tumor cells. The ability to present tumor-associated
      antigens for both induction of antitumor immunity and elicitation of delayed-type
      hypersensitivity was dependent on I-A+ cells and was genetically restricted.
      Finally, dermal cells tended towards eliciting a greater antitumor delayed-type
      hypersensitivity response than epidermal cells. These results show that the
      murine dermis contains antigen-presenting cells capable of processing S1509a
      tumor antigens for the generation of protective antitumor immunity in vivo.

PMID- 10886509
TI  - Increased risk of secondary cancers in patients with primary cutaneous T cell
      lymphoma.
AB  - As putative etiologic factors of primary cutaneous T cell lymphomas may have a
      general cancerogenic effect, we wanted to assess the risk of secondary
      malignancies in 319 patients diagnosed with histopathologically verified
      cutaneous T cell lymphomas and reported to the Finnish Cancer Registry during the
      years 1953-95. Standardized incidence ratios were defined as the ratio of
      observed to expected numbers of cases. To obtain the expected numbers of cancer,
      age-, sex-, and period-specific Finnish incidence rates were applied to the
      appropriate person-years under observation. Ninety-five percent confidence
      intervals were calculated assuming a Poisson distribution. For the whole period,
      we detected 36 secondary cancers whereas 26 were expected (standardized incidence
      ratios 1.4, 95% confidence intervals 1.0-1.9). The overall risk of lung cancer
      was significantly increased (standardized incidence ratio was 2.7, 95% confidence
      intervals were 1.4-4.8); and in particular small-cell lung cancer showed high
      standardized incidence ratios (standardized incidence ratio was 8.5, 95%
      confidence intervals were 2.8-20). Also, the risk of lymphomas was elevated
      (standardized incidence ratios for Hodgkin and non-Hodgkin lymphomas combined
      were 7.0, 95% confidence intervals were 1.9-18). The incidence of other cancers
      was similar to the national ratios. An increased risk of secondary cancers and in
      particular small-cell cancer of the lung and lymphomas among patients with
      primary cutaneous T cell lymphoma is demonstrated. In clinical practice, lung
      cancer and lymphomas must be kept in mind when following up patients with
      cutaneous T cell lymphomas.

PMID- 10886510
TI  - Analysis of the TCRBV repertoire of T cells in normal, human skin: evidence for a
      restricted diversity.
AB  - Alpha beta T cells constitute an important component in the first line of
      immunologic defense in human skin. In order to determine the local selection
      forces driving T cell diversity, we studied the T cell receptor repertoire in
      normal human skin and compared it with that of matched blood samples. Using
      semiquantitative reverse transcription-polymerase chain reaction the expression
      of T cell receptor beta-chain V genes was determined. The majority of skin, but
      not blood T cells, revealed a bias towards usage of T cell receptor beta-chain V2
      and V6. Whereas sequencing of T cell receptor beta-chain V2 and V6 polymerase
      chain reaction products showed a heterogeneous clonal distribution within these
      beta-chain V gene families, the analysis of other selected either over- or
      underrepresented beta-chain V gene families (BV3, BV12, BV13S1, BV17) revealed
      numerous identical T cell receptor beta-chain V transcript sequences that were
      not detected in blood. Restricted T cell receptor diversity in terms of beta
      chain V gene preferences or clonal expansion was observed in skin samples of
      donors from all ages (0.5-87 y). Hence, the repertoire of T cells in normal human
      skin is apparently subjected to skin-specific selection throughout life.
      According to our data, this process could involve superantigens, which favor
      polyclonal accumulation of T cells using certain beta-chain V genes, as well as
      antigens, which induce clonal T cell expansion. Our results furthermore indicate,
      that T cell receptor beta-chain V repertoire restrictions do not necessarily
      result from disease-associated activation of the skin immune system, but could
      reflect regular mechanisms of immunologic homeostasis within the epithelial
      surface of the body.

PMID- 10886511
TI  - Cutaneous T cell lymphoma reactive CD4+ cytotoxic T lymphocyte clones display a
      Th1 cytokine profile and use a fas-independent pathway for specific tumor cell
      lysis.
AB  - We have previously described two cytotoxic T lymphocyte clones isolated from
      lymphocytes infiltrating a human major histocompatibility complex class II-/class
      I+, CD4+ cutaneous T cell lymphoma. These clones displayed a CD4+CD8dim+ (TC5)
      and CD4+ CD8- (TC7) phenotype and mediated a specific major histocompatibility
      complex class I-restricted cytotoxic activity toward Cou-LB autologous tumor cell
      line. Our studies were performed to elucidate the mechanism involved in T-cell
      clone-mediated cytotoxicity and to determine the cytokine profile of both the
      lymphoma cell line and specific cytotoxic T lymphocyte clones. The results
      indicate that, despite surface expression of Fas receptor on Cou-LB and Fas
      ligand induction on TC5 and TC7 cell membranes, the CD4+ cytotoxic T lymphocyte
      clones do not use this cytotoxic mechanism to lyse their specific target. The TC7
      clone uses instead a granzyme-perforin-dependent pathway. Furthermore,
      quantitative analysis of Th1 and Th2 cytokine mRNA expression in the cutaneous T
      cell lymphoma cell line as well as in TC5 and TC7 clones indicated that, whereas
      the tumor cells display a Th2-type profile (interleukin-4, interleukin-6, and
      interleukin-10), the cytotoxic T lymphocyte clones express Th1-type cytokines
      (interferon-gamma, granulocyte macrophage colony stimulating factor, and
      interleukin-2). In addition, preincubation of the tumor-infiltrating lymphocyte
      clones with autologous tumor cells induced their activation and subsequent
      amplification of the Th1-type response. These results indicate a direct
      contribution of the malignant cells in the Th1/Th2 imbalance observed frequently
      in cutaneous T cell lymphoma patients and suggest their potential role in
      depressed cell-mediated immunity. Identification of CD4+ Th1-type cytotoxic T
      lymphocyte clones, the tumor antigen they recognize, and optimization of their
      cytokine expression profile should be useful for the design of new immunotherapy
      protocols in cutaneous T cell lymphoma.

PMID- 10886512
TI  - Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates
      interferon-gamma- and interleukin-4-induced activation of human keratinocytes.
AB  - Interleukin-17 is a T-cell-derived cytokine, detected in skin affected by
      allergic contact dermatitis and psoriasis, which regulates keratinocyte
      expression of adhesion molecules and chemokines. In this study, we have analyzed
      whether interleukin-17 production segregates with a particular T helper (Th) cell
      subset, and have examined the capacity of interleukin-17 to modulate the
      activation of keratinocytes induced by Th1 and Th2 cytokines. A panel of 80
      nickel-specific CD4+ T cell clones (36 Th0, 30 Th1, and 14 Th2) was isolated from
      peripheral blood or lesional skin of allergic contact dermatitis patients.
      Significant amounts (> 50 pg per ml) of interleukin-17 were released by about 50%
      of activated Th0, Th1, and Th2 cells. Interleukin-17 alone and in cooperation
      with interleukin-4, or to a lesser extent with interferon-gamma, decreased the
      interleukin-1 receptor antagonist to interleukin-1alpha ratio in the supernatants
      as well as in cell lysates from keratinocytes. In addition, interleukin-17
      stimulated the release of growth-regulated oncogene-alpha, granulocyte-macrophage
      colony stimulating factor, and interleukin-6, with synergistic or additive
      effects when used together with interferon-gamma or interleukin-4. Interleukin-17
      and interleukin-4 also increased stem cell factor release, a function that was
      inhibited by interferon-gamma. Moreover, interleukin-17 and interleukin-4
      enhanced interferon-gamma-induced expression of intercellular adhesion molecule
      1, but not CD40, on keratinocytes. The constitutive expression of interleukin-17
      and interferon-gamma receptors on keratinocytes was not modulated by interleukin
      17, interferon-gamma, or interleukin-4, whereas the interleukin-4 receptor was
      significantly downregulated by interferon-gamma. As a whole, the results indicate
      that interleukin-17 can participate relevantly in T-cell-mediated skin immune
      responses by amplifying both interferon-gamma- and interleukin-4-induced
      activation of keratinocytes.

PMID- 10886513
TI  - Protein phosphatase type 1-dependent dephosphorylation of the retinoblastoma
      tumor suppressor protein in ultraviolet-irradiated human skin and keratinocytes.
AB  - This study provides evidence for the involvement of a type 1 protein
      serine/threonine phosphatase in the ultraviolet radiation-induced
      dephosphorylation of retinoblastoma tumor suppressor protein in human skin and
      cultured keratinocytes. The retinoblastoma gene product was localized to the
      nuclei and nucleoli of keratinocytes, and to the nuclei of basal and spinous
      layer cells of normal human epidermis. Western blot analysis of the
      retinoblastoma tumor suppressor protein antigen from keratinocytes and skin
      established the presence of the hypophosphorylated and hyperphosphorylated forms
      of retinoblastoma tumor suppressor protein. The exposure of keratinocytes and
      human skin to 200 J per cm2 of ultraviolet radiation, resulted in a rapid
      depletion in hyperphosphorylated retinoblastoma tumor suppressor protein, and the
      accumulation of growth inhibitory hypophosphorylated retinoblastoma tumor
      suppressor protein(105). In unirradiated and ultraviolet-irradiated keratinocytes
      retinoblastoma tumor suppressor protein was localized to the spindles of M-phase
      cells. In contrast, the exposure of keratinocytes to ultraviolet in the presence
      of 5 mM okadaic acid, resulted in an inhibition of retinoblastoma tumor
      suppressor protein translocation to the mitotic spindles of M-phase
      keratinocytes. In addition, the ultraviolet radiation-induced depletion in
      hyperphosphorylated retinoblastoma tumor suppressor protein, and accumulation of
      hypophosphorylated retinoblastoma tumor suppressor protein(105) was inhibited by
      5 mM okadaic acid. Okadaic acid (0.5 nM), however, did not affect the ultraviolet
      radiation-induced dephosphorylation and depletion of hyperphosphorylation of the
      retinoblastoma tumor suppressor protein. Western blot analysis of ultraviolet
      irradiated keratinocytes demonstrated that the hypophosphorylated growth
      inhibitory 105 kDa form of retinoblastoma tumor suppressor protein
      coimmunoprecipitated with the 38 kDa catalytic subunit of a type 1 protein
      serine/threonine phosphatase.

PMID- 10886514
TI  - Levels and repair of cyclobutane pyrimidine dimers and 6-4 photoproducts in skin
      of sporadic basal cell carcinoma patients.
AB  - The 32P-postlabeling method was applied to measure directly the levels and repair
      rates of specific cyclobutane pyrimidine dimers and 6-4 photoproducts in 10 basal
      cell carcinoma patients and 10 controls matched on age, skin type, and gender
      after exposure to 400 J per m2 of solar simulating radiation on previously
      unexposed buttock skin. The results showed an identical level of photoproducts at
      0 h after solar simulating radiation in the basal cell carcinoma group and the
      control group. Erythemal response correlated with the repair of cyclobutane
      pyrimidine dimers within 24 h in both groups, i.e., repair was faster in those
      with a strong erythemal reaction. The basal cell carcinoma patients showed a
      somewhat slower repair of photoproducts in skin compared with the controls, but
      the result was not significant. Photoproducts formed at the TTC sites were
      repaired faster than those at the TTT sites for both cyclobutane pyrimidine
      dimers and 6-4 photoproducts in the basal cell carcinoma group and in the
      controls.

PMID- 10886515
TI  - Endogenous skin fluorescence is a good marker for objective evaluation of
      comedolysis.
AB  - OBJECTIVE: evaluation of comedone lesions, especially in vivo, remains a
      challenge. We have used the rhino mouse model in combination with topical
      application of all-trans retinoic acid as a comedolytic agent, to investigate the
      potential of fluorescence spectroscopy as a noninvasive technique in the
      assessment of noninflammatory acne. The results indicate that there is a strong
      correlation between the fluorescence excitation spectral features assessed in
      vivo, and the histologic changes identified, particularly the size of the
      utriculi as well as the dermal and epidermal thickness. We conclude that
      fluorescence excitation spectroscopy represents a promising novel and useful tool
      in the quantitative evaluation of the pseudocomedones and could also be used for
      the rapid and noninvasive assessment of comedolysis induced by the application of
      pharmacologic agents such as retinoids.

PMID- 10886516
TI  - Cell-density-dependent regulation of expression and glycosylation of dopachrome
      tautomerase/tyrosinase-related protein-2.
AB  - The expression of the dopachrome tautomerase gene (Dct) and its protein product,
      tyrosinase-related protein-2, was studied in the cultured, phorbol-ester
      dependent murine melanocyte cell line melan-a. Increased cell density was found
      to stimulate Dct expression both in cells stably transfected with a Dct promoter
      lacZ construct and endogenously in nontransfected cells. Increased Dct expression
      under these conditions corresponds to increased tyrosinase-related protein-2
      production. Tyrosinase-related protein-2 was found to exist in two distinct
      glycoforms with different endoglycosidase sensitivities. Density-dependent
      expression of tyrosinase-related protein-2 was independent of time of cell
      growth, cell proliferation, and soluble factors, implying that cell-cell contact
      is the important determinant governing increased Dct expression under these
      conditions. Tyrp1 gene expression and tyrosinase-related protein-1 production
      were also induced under similar conditions. The results show that cell-cell
      contact between melanocytes induces a coordinated response at both
      transcriptional and nontranscriptional levels that induces production of the
      tyrosinase-related proteins that have a significant role in melanization.

PMID- 10886517
TI  - Role of Sp1 response element in transcription of the human transglutaminase 1
      gene.
AB  - This study addresses the contribution of an Sp1 response element in the proximal
      promoter of the transglutaminase 1 gene to transcription in normal epidermis and
      in a case of lamellar ichthyosis lacking transglutaminase 1 activity. The latter
      exhibited an Sp1 promoter mutation previously hypothesized to suppress
      transcription. In this study, several experiments indicated that the native Sp1
      response element was functional, but it had only a small influence on
      transcription, and the previously observed mutation had no effect. These
      experiments involved mobility shift assays and transfections of promoter
      constructs in which the Sp1 site was mutated or lacking altogether. In addition
      the proximal 1.6 kb of the promoter from the affected individual was as active in
      transfections as the promoter from unaffected individuals. A search for sequence
      alterations in mRNA transcribed in keratinocytes from the patient revealed a
      novel single base mutation in codon 661 of the transglutaminase coding region
      predicted to result in premature termination of protein translation. The presence
      of this mutation in parental genomic DNA was confirmed by restriction digestion.
      Thus the lamellar ichthyosis phenotype in this case is likely attributable to a
      novel non-sense mutation in the coding region leading to reduced transglutaminase
      1 mRNA levels rather than mutation of the Sp1 site.

PMID- 10886518
TI  - Expression patterns of placenta growth factor in human melanocytic cell lines.
AB  - Expression patterns of the angiogenic placenta growth factor and its receptor
      neuropilin-1 were assessed in normal human melanocytes, SV40T-transformed
      melanocytes, and melanoma cells derived from primary and metastatic lesions. As
      determined by reverse transcription-polymerase chain reaction all primary and
      metastatic melanoma cell lines tested and SV40T-transformed melanocytes
      coexpressed two placenta growth factor splice variants (placenta growth factor-1
      and -2) as well as neuropilin-1 mRNA. Placenta growth factor protein was detected
      in conditioned media derived from five of eight melanomas and from SV40T
      transformed melanocytes. In contrast to melanoma cells, normal melanocytes did
      not express placenta growth factor mRNA at detectable levels and did not secrete
      placenta growth factor protein. By contrast, neuropilin-1 transcripts were
      detected in some of the normal melanocytes. Secretion of placenta growth factor
      by melanoma cells appeared to be constitutive because it was not affected by the
      addition of exogenous growth factors including insulin, epidermal growth factor,
      or basic fibroblast growth factor to culture media. Although melanoma cells
      expressed both, neuropilin-1 and flt-1, exogenous homodimeric placenta growth
      factor had no effect on melanoma cell growth. Similarly, placenta growth factor
      did not induce urokinase-type plasminogen activator production in these cells.
      These findings demonstrate that melanoma progression is accompanied by
      deregulated, constitutive placenta growth factor expression. Placenta growth
      factor, however, serves no apparent autocrine role in melanoma proliferation.
      Further studies are needed to define the relative contribution of placenta growth
      factor to the angiogenic properties of human melanomas.

PMID- 10886519
TI  - Communication: papillomavirus DNA in basal cell carcinomas of immunocompetent
      patients: an accidental association?TITLE.
AB  - DNA of human papillomaviruses has frequently been detected in nonmelanoma skin
      cancers, raising the question of a possible causal contribution of these tumor
      viruses to skin carcinogenesis. Basal cell carcinomas are the most common
      nonmelanoma skin cancers; however, so far they are only poorly analyzed with
      regard to human papillomavirus infection. We searched for human papillomavirus
      DNA in 69 biopsies from 61 immunocompetent basal cell carcinoma patients from two
      geographic locations in Europe using six different polymerase chain reaction
      primer systems. We could demonstrate human papillomavirus-DNA in 43.5% of the
      tested tumors. Human papillomavirus positivity did not seem to correlate with the
      duration of disease or patients' age. The vast majority of virus types in the
      biopsies belonged to the group of epidermodysplasia verruciformis-associated
      human papillomavirus. Of 31 sample pairs tested for human papillomavirus-DNA in
      tumors as well as in perilesional healthy skin, seven carried viral sequences in
      lesional and healthy skin and three only in the basal cell carcinoma. Six of the
      seven human papillomavirus-positive basal cell carcinoma/healthy skin pairs
      contained identical human papillomavirus types in tumors and histologically
      normal tissue. Forty basal cell carcinoma patients were additionally analyzed for
      IgG antibodies against virus-like particles of three representative
      epidermodysplasia verruciformis-human papillomavirus types: 8, 15, and 36. No
      statistically significant differences could be detected between human
      papillomavirus antibody prevalences of basal cell carcinoma patients and of
      dermatologically healthy individuals. Moreover, serologic findings did not
      correlate with the detection of specific human papillomavirus types in tumors.
      Our results seem to suggest that the occurrence of human papillomavirus-DNA in
      basal cell carcinoma does not reflect a major etiologic role of human
      papillomavirus in this cancer.

PMID- 10886520
TI  - Presence of resin acids in "Oakmoss" patch test material: a source of
      misdiagnosis?

PMID- 10886521
TI  - Downregulation of tyrosinase activity in human melanocyte cell cultures by
      yohimbine.

PMID- 10886522
TI  - Low-intensity laser therapy for recurrent herpes labialis.

PMID- 10886523
TI  - Reply

PMID- 10886524
TI  - Expression of cytokeratins and cornified cell envelope-associated proteins in
      umbilical cord epithelium: a comparative study of the umbilical cord, amniotic
      epithelia and fetal skin.

PMID- 10886525
TI  - Inherited dystrophic epidermolysis bullosa in inbred dogs: A spontaneous animal
      model for somatic gene therapy.

PMID- 10886526
TI  - Immunocytochemical strategies for electron microscopy: choice or compromise.
AB  - This review attempts to describe the major immunocytochemical strategies that are
      in current use for transmission electron microscopy. Emphasis is placed on
      suggesting the most appropriate application of each technique that is described.
      The review is not intended to identify the microscopist's 'cure all' technique
      for immunocytochemistry but rather to describe what techniques are available and
      what are their relative merits. Expensive equipment and technically complicated
      methods are not always necessary to collect robust data. I hope to present a
      review that will enable its readers to select the most profitable technique (or
      compromise) available, to reflect both their resources and their ability to
      address their biological questions with vigour.

PMID- 10886527
TI  - Microcalorimeter energy-dispersive spectrometry using a low voltage scanning
      electron microscope
AB  - We describe the current performance of the prototype microcalorimeter energy
      dispersive spectrometer (&mgr;cal EDS) developed at NIST for X-ray microanalysis.
      We show that the low-energy &mgr;cal EDS, designed for operation in the energy
      range 0.2-2 keV, offers significant advantages for low-beam-energy microanalysis.
      We present several examples in which the prototype &mgr;cal EDS has been used to
      solve problems in low-voltage microanalysis, including the analysis of tungsten
      silicide (WSi2), titanium nitride (TiN) and barium titanate (BaTiO3) and the
      measurement of chemical shifts in Fe and C compounds.

PMID- 10886528
TI  - Quantification of boundary segregation in the analytical electron microscope
AB  - When studying equilibrium grain-boundary segregation using the small (
      approximately 1 nm) electron probe of the scanning transmission electron
      microscope and X-ray energy dispersive spectroscopy, the assumptions made about
      the size and shape of the beam-specimen interaction volume may introduce errors
      in quantification of up to a factor of five. Comparisons between experimental
      segregation profiles and different theoretical models have shown that a Gaussian
      model for the electron distribution will provide the best description for the
      interaction volume. Calculations of minimum detectable segregation levels have
      shown that optimum sensitivity is not achieved in the thinnest samples or even
      with the smallest probe sizes. In addition, operating at 300 keV (rather than 100
      keV) will halve the minimum detectable segregation level, assuming all other
      experimental conditions are equal. Rastering the electron probe over a fixed area
      while acquiring spectra improves the accuracy of quantification but at the price
      of reducing sensitivity by at least a factor of three.

PMID- 10886529
TI  - Adhesion of microbes using 3-aminopropyl triethoxy silane and specimen
      stabilisation techniques for analytical transmission electron microscopy.
AB  - A variety of adhesive support-films were tested for their ability to adhere
      various biological specimens for transmission electron microscopy. Support films
      primed with 3-amino-propyl triethoxy silane (APTES), poly-L-lysine, carbon and
      ultraviolet-B (UV-B)-irradiated carbon were tested for their ability to adhere a
      variety of biological specimens including axenic cultures of Bacillus subtilis
      and Escherichia coli and wild-type magnetotactic bacteria. The effects of UV-B
      irradiation on the support film in the presence of air and electrostatic charge
      on primer deposition were tested and the stability of adhered specimens on
      various surfaces was also compared. APTES-primed UV-B-irradiated Pioloform was
      consistently the best adhesive, especially for large cells, and when adhered
      specimens were UV-B irradiated they became remarkably stable under an electron
      beam. This assisted the acquisition of in situ phase-contrast lattice images from
      a variety of biominerals in magnetotactic bacteria, in particular metastable
      greigite magnetosomes. Washing tests indicated that specimens adhering to APTES
      primed UV-B-irradiated Pioloform were covalently coupled. The electron beam
      stability was hypothesised to be the result of mechanical strengthening of the
      specimen and support film and the reduced electrical resistance in the specimen
      and support film due to their polymerization and covalent coupling.

PMID- 10886530
TI  - Atomic force microscopy studies of intercalation-induced changes in plasmid DNA
      tertiary structure.
AB  - Structural transitions in the tertiary structure of plasmid DNA have been
      investigated using atomic force microscopy. Changes in superhelical stress were
      induced by ethidium bromide intercalation, and conformational effects monitored
      by recording topographic images from DNA complexes of various ethidium
      bromide:base pair stoichiometry. Significant changes in the tertiary structure of
      individual DNA molecules were observed with increasing ethidium bromide
      concentration. The first distinct conformational transition was from a
      predominantly relaxed structure to one consisting solely of toroidal supercoils.
      A further increase in ethidium bromide concentration resulted in the formation of
      regions of plectonemic supercoiling. The ratio of plectonemic:toroidal
      supercoiling gradually increased until an extremely tightly interwound structure
      of solely plectonemic supercoiling was finally adopted. The toroidal form of
      supercoiling observed in this study is unusual as both atomic force microscopy
      and electron microscopy techniques have previously shown that plectonemic
      supercoiling is the predominant form adopted by plasmid DNA.

PMID- 10886531
TI  - Using the Hilbert transform for 3D visualization of differential interference
      contrast microscope images.
AB  - Differential interference contrast (DIC) is frequently used in conventional 2D
      biological microscopy. Our recent investigations into producing a 3D DIC
      microscope (in both conventional and confocal modes) have uncovered a fundamental
      difficulty: namely that the phase gradient images of DIC microscopy cannot be
      visualized using standard digital image processing and reconstruction techniques,
      as commonly used elsewhere in microscopy. We discuss two approaches to the
      problem of preparing gradient images for 3D visualization: integration and the
      Hilbert transform. After applying the Hilbert transform, the dataset can then be
      visualized in 3D using standard techniques. We find that the Hilbert transform
      provides a rapid qualitative pre-processing technique for 3D visualization for a
      wide range of biological specimens in DIC microscopy, including chromosomes,
      which we use in this study.

PMID- 10886532
TI  - Doctor-to-patient transmission of viral hepatitis B: is it a problem, is there a
      solution?
AB  - It is well-established that hepatitis B may be transmitted from surgeons to their
      patients. Clear strategies are needed to reduce the risk of transmission whilst
      not discriminating unnecessarily against surgeons who may pose no risks to their
      patients. This review outlines the current position and provides a blueprint for
      action that may reduce the risks to patients whilst minimizing the impact on
      practising surgeons.

PMID- 10886533
TI  - Genotype and viral load as prognostic indicators in the treatment of hepatitis C.
AB  - Interferon-alpha (IFN-alpha), either alone or in combination with ribavirin, is
      the standard treatment for patients with hepatitis C. However, most patients do
      not achieve a sustained remission with this treatment regimen. A number of
      studies have demonstrated that genotype, baseline viral load and/or a decrease in
      viral load early after treatment induction are the major predictive factors for
      response to treatment with IFN. Patients with hepatitis C virus (HCV) genotype 1
      are more resistant to treatment with IFN, whereas low viral load at baseline and
      a marked decline in the HCV RNA level during the first 2-12 weeks of IFN therapy
      are associated with enhanced treatment efficacy. These variables could
      potentially be used to develop treatment algorithms that tailor therapies for
      specific clinical situations. Continued development and refinement of such
      algorithms would facilitate both the selection of patients who are most likely to
      benefit from therapy and the development of optimal treatment regimens for
      different patient groups. Predictive factors will also enable clinicians to
      identify subsets of patients who are not expected to respond well to current
      treatment. The development of new delivery methods for IFN that produce sustained
      antiviral pressure may provide a means of treating these previously difficult-to
      treat patient groups.

PMID- 10886534
TI  - Hepatitis B virus DNA levels, precore mutations, genotypes and histological
      activity in chronic hepatitis B.
AB  - The present study aimed to clarify how viraemia levels reflect the clinical
      stages of chronic hepatitis B virus (HBV) infection, in particular studying
      whether 'healthy carriers' can be identified by analysing HBV DNA levels with a
      highly sensitive quantitative assay. Histology activity index (HAI), alanine
      aminotransferase (ALT) level, genotype and precore mutations were compared with
      the HBV DNA level, as measured using the Amplicor HBV Monitor assay in a
      prospective study. In 124 hepatitis B e antigen-negative (HBeAg-) patients, the
      majority with mild liver disease, log HBV DNA levels showed a Gaussian
      distribution around a geometric mean of 33 000 genome copies ml-1, and increasing
      HBV DNA level was associated with significantly higher inflammation (HAIinfl) and
      fibrosis (HAIfibr) scores and higher ALTi (ALT / the upper reference value).
      Severe inflammation (HAIinfl > or = 7) was seen in 83% (five of six), 36% (eight
      of 22) and 3% (one of 37) of HBeAg- patients with HBV DNA > 107, > 2 x 105 and <
      104 copies ml-1, respectively. In severe HBeAg- hepatitis, patients with precore
      wild-type infection had lower HBV DNA levels than those with precore mutants. In
      36 HBeAg-positive (HBeAg+) patients, no correlation between HBV DNA level and
      liver damage was seen. Ninety-six per cent of HBeAg- patients with ALTi < 0.5 had
      HAIinfl < or = 3. In HBeAg- carriers with ALTi 0.5-1.0, the relative risk for
      severe inflammation, comparing HBV DNA > 2 x 105 copies ml-1 vs < 2 x 105 copies
      ml-1, was 14.7. In conclusion, in HBeAg- carriers, HBV DNA < 104 copies ml-1 or
      ALTi < 0.5 indicates mild inflammation, while > 2 x 105 copies ml-1 of HBV DNA
      may justify further investigations. Precore status may be relevant for the
      interpretation of viraemia.

PMID- 10886535
TI  - Natural course of progression of liver fibrosis in Japanese patients with chronic
      liver disease type C--a study of 527 patients at one establishment.
AB  - Patients with chronic hepatitis C infection show a gradual progression of
      fibrosis to liver cirrhosis and hepatocellular carcinoma (HCC). We studied
      whether the progression of liver fibrosis differed among Japanese subjects who
      were infected with different hepatitis C virus (HCV) genotypes. In 527 patients
      we examined whether there was a relationship between gender, age, history of
      blood transfusion, interval between date of blood transfusion and date of liver
      biopsy or date of diagnosis of HCC, serum alanine aminotransferase level,
      platelet count or HCV genotype, with the extent of liver fibrosis, classified
      into four stages (F1-F4). Moreover, we compared the mean rate of liver fibrosis
      progression per year in patients with each HCV genotype. Patients who had a
      higher fibrosis score tended to be older, have a lower platelet count and a
      longer interval since blood transfusion than those who had a lower fibrosis
      score. The mean rate of liver fibrosis progression was 0.12 +/- 0.15 stages per
      year after the blood transfusion. However, the progression rate of liver fibrosis
      in patients who had received a blood transfusion when they were > or = 30 years
      of age was 0.19 +/- 0.22, while the progression rate of liver fibrosis in the
      patients who had received a blood transfusion when they were < 30 years was 0.09
      +/- 0.09. In conclusion, chronic hepatitis C is a progressive disease, and
      patients with genotype 1b, 2a and 2b have a similar rate of progression of liver
      fibrosis. Particular attention should be paid to patients who are infected with
      HCV when > or = 30 years of age, because intrahepatic fibrosis rapidly progresses
      in these patients.

PMID- 10886536
TI  - Phylogenetic evidence, by multiple clone analysis of hypervariable region 1, for
      the transmission of hepatitis C virus to chronic haemodialysis patients.
AB  - We analysed hepatitis C virus (HCV) sequences to determine whether nosocomial
      transmission of HCV occurred in a haemodialysis unit. Twenty patients positive
      for serum HCV RNA were investigated. All were undergoing haemodialysis therapy in
      the same room. The hypervariable region 1 (HVR1) sequence of HCV was amplified
      and multiple clones sequenced. Phylogenetic analysis of these sequences revealed
      five genetic clusters consisting of HCV isolates from 11 of the 20 patients. In
      addition to two genetic clusters of HCV isolates from the four currently
      seroconverting patients and another patient who had been persistently infected,
      we identified three other phylogenetic relationships in HCV isolates from six
      patients. The patients grouped into the same cluster received haemodialysis
      individually on the same shift and/or side-by-side. Phylogenetic analysis of HCV
      HVR1 sequences corroborated the patient-to-patient HCV transmission suggested by
      an epidemiological study and that unrecognized transmission of HCV occurs in the
      dialysis room. Our multiple clone analysis of HCV isolates provides detailed
      information on nosocomial transmission of HCV. Transmission occurs more
      frequently when treatment is performed at the same time than in consoles located
      close to each other.

PMID- 10886537
TI  - The stability of hepatitis C virus RNA after storage at +4 degrees C.
AB  - One of the major issues in nucleic acid testing is how to store blood samples to
      obtain reliable results. We therefore studied hepatitis C virus (HCV) RNA
      concentration in samples after storage at +4 degrees C or freezing and thawing.
      Six HCV RNA-positive, untreated subjects were studied. Blood samples were
      collected from these subjects in plasma preparation tubes. The HCV RNA
      concentration was analysed after storage at +4 degrees C for 168 h or after five
      freeze-thaw cycles. For HCV RNA quantification we used a qualitative and a
      quantitative commercial test. After 168 h of storage at +4 degrees C, the HCV RNA
      concentration was similar to that observed at time-point 0 (5.025 log vs 5.492
      log). In one sample we observed a significant fall in HCV RNA concentration.
      After five freeze-thaw cycles, the HCV RNA concentration was lower than that
      observed at time-point 0 (4.454 log vs 5.492 log) and in four samples we observed
      a significant fall in HCV RNA concentration. Our data suggest that HCV RNA is
      stable in whole blood samples stored at +4 degrees C for 168 h. Based on our
      results, we conclude that the standard procedures for transport of blood samples
      (at room temperature for a maximum of 5 h) and storage schedules (+4 degrees C
      for a maximum of 48 h) can be maintained without compromising the quality of
      results.

PMID- 10886538
TI  - Treatment of chronic hepatitis C genotype IV with interferon-ribavirin
      combination in Saudi Arabia: a multicentre study.
AB  - Between 1996 and 1997, we conducted a multicentre study to assess the effect of
      combination therapy of interferon (IFN) + ribavirin on chronic hepatitis C
      genotype 4. Ninety-seven patients were enrolled. Sixty-eight patients (47 male
      and 21 female) were non-responders to previous therapy with IFN (Group I). Twenty
      nine patients (19 male and 10 female) were new (Group II). Following treatment
      with IFN, 23% in Group I and 9% in Group II had a sustained biochemical response.
      Only 12% in Group I and 5% in Group II achieved a sustained virological response.
      Virus load was found to be the major factor determining response, followed by
      histology grading and staging. Like HCV genotype 1, HCV genotype 4 seems to have
      a poor response to therapy.

PMID- 10886539
TI  - Intrahepatic transfusion-transmitted virus detected by in situ hybridization in
      patients with liver diseases.
AB  - Transfusion-transmitted virus (TTV) has been identified from patients with post
      transfusion hepatitis of unknown aetiology, but the clinical relevance remains
      unclear. The aim of this study was to evaluate TTV in liver. We studied 15
      patients with hepatitis non-A-E and 44 with hepatitis B virus (HBV). The nested
      polymerase chain reaction (PCR) with primers corresponding to the conserved
      region of the published TTV genome was employed to amplify TTV fragments in
      serum, and in situ hybridization was used to detect TTV in biopsied liver
      specimens. TTV DNA was detected in serum from six (40%) of 15 patients with
      hepatitis of unknown aetiology and from 16 (36.4%) of 44 patients with chronic
      hepatitis B, respectively. The intrahepatic viral fragment was detected in 17
      (77.3%) of 22 patients with TTV in serum. There was no statistical difference in
      the prevalence of TTV infection between the two groups (hepatitis non-A-E 40% vs
      HBV 25%, P > 0.75). When patients in both groups, with and without TTV, were
      compared, no differences were found in serum alanine aminotransferase (ALT)
      levels (hepatitis non-A-E: 131.5 +/- 66.6 vs 244.2 +/- 257.4, P=0.955; HBV: 240.1
      +/- 418.9 vs 214.6 +/- 276.7 U l(-1), P=0.761) or histological activity index
      (grade) score (hepatitis non-A-E: 6.4 +/- 5.5 vs 5.6 +/- 5.9, P=0.689; HBV: 5.6
      +/- 3.7 vs 5.5 +/- 3.7, P=0.345). HBV DNA levels in patients with and without TTV
      co-infection did not differ significantly (300 +/- 776.4 microg ml(-1) vs 97.1 +/
      160.5 microg ml(-1), P=0.980). Hence, TTV does exist in liver, but plays no role
      in hepatitis or aggravation of liver damage when co-infected with HBV.

PMID- 10886540
TI  - Hepatitis C is more severe in drug users with human immunodeficiency virus
      infection.
AB  - Drug users with chronic hepatitis C virus (HCV) infection are frequently co
      infected with human immunodeficiency virus-1 (HIV-1), but it is still not clear
      whether HIV-1 worsens the natural history of hepatitis C. To investigate this, we
      conducted a multicentre observational study in 163 drug addicts with
      histologically documented hepatitis C, 92 of whom were also infected with HIV-1:
      25 (27%) were CDC stage II, 53 (58%) were CDC stage III and 14 (15%) were CDC
      stage IV. Eighty-eight (54%) patients had chronic hepatitis (CH) with minimal
      activity, 28 (17%) had CH with moderate activity, 40 (25%) had CH with severe
      activity and seven (4%) had active cirrhosis. Twenty-one HIV-negative patients
      and 15 HIV-positive patients admitted to alcohol abuse (29% vs 16%, P=0.0665).
      Liver disease was more severe in HIV-positive patients than in HIV-negative ones
      (P=0.0198): 34 HIV-positive patients and 13 HIV negatives had severe CH and
      cirrhosis. These two severe liver diseases were seen more often in HIV-positive
      patients with a history of alcohol abuse than in HIV-negative patients (10 out of
      16 vs seven out of 21). Age, alcohol abuse and distribution of the histological
      categories of liver disease were statistically different in HIV-infected and HIV
      uninfected patients. Multivariate analysis showed that age, alcohol abuse and
      serum antibodies to HIV were independently associated with severe CH or
      cirrhosis. Thus, HIV may enhance the risk of severe liver disease in drug users
      with hepatitis C, independently of the degree of immune dysfunction. Alcohol
      abuse may contribute independently, aggravating the cause of HCV-dependent liver
      disease.

PMID- 10886541
TI  - Hepatitis C virus co-infection is a negative prognostic factor for clinical
      evolution in human immunodeficiency virus-positive patients.
AB  - A longitudinal study of human immunodeficiency virus (HIV)-infected individuals
      followed-up in 13 centres was performed to assess the influence of hepatitis C
      virus (HCV) on the clinical and immunological evolution of HIV-infected patients.
      Eight-hundred and twelve HIV-infected patients with known HIV acquisition date,
      89 co-infected with HCV, were included in the cohort. Clinical progression was
      defined as: 30% decrease of Karnofsky's index; and/or 20% body weight loss;
      and/or acquired immune deficiency syndrome (AIDS)-defining illness; and/or death
      (except by accident, suicide, or overdose). Immunological progression was defined
      as a decrease of initial CD4 count to below 200 mm(-3). If immunological
      progression was not statistically different between groups (P=0.25), clinical
      progression was significantly faster in HCV-HIV co-infected patients in
      univariate (P=0.02) and multivariable survival analysis (hazard ratio=1.63,
      P=0.03). This argues for active management of hepatitis C chronic infection among
      HCV-HIV co-infected patients.

PMID- 10886542
TI  - Epidemiological survey and follow-up of transfusion-transmitted virus after an
      outbreak of enterically transmitted infection.
AB  - An outbreak of enterically transmitted hepatitis occurred during 1996 among
      students at a vocational school. Viral fragments homologous to transfusion
      transmitted virus (TTV) were detected in faeces. To elucidate the endemic status,
      an epidemiological survey and case follow-up after the outbreak were carried out.
      During and after the outbreak, virus carriers among staff were, respectively,
      32.1% and 31.3% in serum, and 24.6% and 18.2% in faeces. After the last outbreak,
      attacks were still occurring among new students with an incidence of 2.4% in 1997
      and 2.3% in 1998. There was also a small-scale outbreak in 1998 with a prevalence
      of 17.9%. On follow-up at 6 and 18 months after onset, alanine aminotransferase
      (ALT) elevation was found in 29.7% and 13.9% of patients. At 6 months, viral
      fragments were detected in serum in 78.1% and 46.7% of patients, with and without
      ALT elevation, respectively. At 18 months the corresponding figures were 55.6%
      and 19.2%, respectively. At the 18-month follow-up, viral fragments were detected
      in faeces in 29.6% and 19.3% of patients with and without ALT elevation. In
      conclusion, this disease might be transmitted from asymptomatic virus carriers.
      According to the laboratory data, both parenteral and non-parenteral
      transmissions are involved, and the faecal-oral route might be more important.

PMID- 10886543
TI  - Infections with hepatitis B and C viruses in patients on maintenance dialysis in
      Romania and in former communist countries: yellow spots on a blank map?
AB  - We studied prospectively, between 1993 and 1998, the prevalence and incidence of
      markers against hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D
      virus (HDV), in 180 patients with chronic renal failure, dialysed in the
      Nephrological Clinic, Cluj. HBV and HCV markers were common in the patients who
      were already on haemodialysis in 1993 (antibodies to hepatitis B core antigen
      [HBcAb]: 57.9-88%; hepatitis B surface antigen [HBsAg]: 8.7-25%; antibodies to
      HCV [anti-HCV]: 73.7-100%; simultaneous occurrence of HBsAg and anti-HCV
      antibodies: 4.4-21%). These patients had the longest mean duration of
      haemodialysis therapy (6.79 +/- 4.82 years). The lowest prevalence was found in
      1996, in the groups of patients included in the haemodialysis programme between
      1993 and 1996 (HBcAb: 2.2-3.3%; HBsAg: 0-2.2%; anti-HCV antibodies: 0-2.2%; HBsAg
      and anti-HCV antibodies: 0-2.2%). The patients included since 1996 had, again, a
      high prevalence of markers (HBsAg: 21.6%; anti-HCV antibodies: 28.6%), despite
      the short duration of dialysis therapy (1.65 +/- 1.18 years). The incidence of
      infection was high before 1993, fell markedly between 1993 and 1996 (zero for the
      HBsAg and 6. 67% year-1 for the anti-HCV antibodies) and rose sharply between
      1996 and 1998 (10.2%, respectively 29% year-1). The prevalence of HBV and HCV
      infections did not correlate with the age of the patients and depended, but only
      up to 1993, on the quantity of transfused blood. The link between the duration of
      the haemodialysis and the prevalence of the HBV and/or HCV infection proved
      nosocomial transmission. The very high prevalence and incidence of HBV and HCV
      infections, surpassing not only Western countries, but even those of 'developing'
      countries that are endemic for these infections, is characteristic of some former
      communist countries. A radical reform of the medical system in these countries is
      required.

PMID- 10886544
TI  - Protein metabolism in patients with chronic renal failure: role of uremia and
      dialysis.
AB  - Individuals with chronic renal failure (CRF) have a high prevalence of protein
      energy malnutrition. There are many causes for this condition, chief among which
      is probably reduced nutrient intake from anorexia. In nondialyzed patients with
      CRF, energy intake is often below the recommended amounts; in maintenance
      dialysis patients, both dietary protein and energy intake are often below their
      needs. Although a number of studies indicate that rats with CRF have increased
      protein catabolism in comparison to control animals, more recent evidence
      suggests that increased catabolism in CRF rats is largely if not entirely due to
      acidemia, particularly if these animals are compared to pair-fed control rats.
      Studies in humans with advanced CRF also indicate that acidemia can cause protein
      catabolism. Indeed, nitrogen balance studies and amino acid uptake and release
      and isotopic kinetic studies indicate that in nondialyzed individuals with CRF,
      who are not acidemic, both their ability to conserve body protein when they
      ingest low protein diets and their dietary protein requirements appear to be
      normal. For patients undergoing maintenance hemodialysis or chronic peritoneal
      dialysis, dietary protein requirements appear to be increased. The increased need
      for protein is due, in part, to the losses into dialysate of such biologically
      valuable nitrogenous compounds as amino acids, peptides, and proteins. However,
      the sum of the dietary protein needs for CRF patients (of about 0.60 g/kg/day)
      and the dialysis losses of amino acids, peptides and proteins do not equal the
      apparent dietary protein requirements for most maintenance dialysis patients.
      This discrepancy may be due to a chronic state of catabolism in the clinically
      stable maintenance dialysis patient that is not present in the clinically stable
      nondialyzed individual who has advanced CRF. Possible causes for such a low grade
      catabolic state include resistance to anabolic hormones (for example, insulin,
      IGF-1) and a chronic inflammatory state associated with increased levels of pro
      inflammatory cytokines.

PMID- 10886545
TI  - Sphingolipids.
AB  - A significant corpus of work over the last decade has firmly established an
      important role for sphingolipids in a variety of important biological processes.
      Such processes include signaling events related to cell growth, differentiation,
      programmed cell death, and stress responses. These processes not only involve
      those sphingolipids that accumulate as a result of a variety of inherited
      lysosomal storage disorders, but, in addition, sphingolipids associated with long
      chain base metabolism. This article reviews the chemical properties, pathways,
      regulated metabolism, and signaling function of sphingolipids. In addition, the
      potential roles of sphingolipids in renal-specific processes are considered.
      While a variety of cellular functions have been ascribed to sphingolipids, in
      many cases proof of the concept has yet to be well established. Thus, a number of
      critical questions can be posed in interpreting these studies. Several of these
      questions are considered.

PMID- 10886546
TI  - Expression of mitogen-activated protein kinase family in rat renal development.
AB  - BACKGROUND: Among mitogen-activated protein kinase (MAPK) family members,
      extracellular signal-regulated kinase (ERK) promotes proliferation or
      differentiation, whereas c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) are
      thought to inhibit cell growth and induce apoptosis. MAPK phosphatase-1 (MKP-1)
      inactivates and modulates MAPKs. During renal development, large scale
      proliferation and apoptosis occur. We investigated the temporal and spatial
      expression patterns of MAPKs and MKP-1 in rat kidney during development. METHODS:
      Western blot analysis and immunohistochemistry were performed in the developing
      and mature kidney of the rat. RESULTS: The expression of ERK, p38, and MKP-1 were
      high in developing kidney. On the other hand, JNK was abundantly expressed in
      adult kidney. Active forms of ERK, p38, and JNK correlated with the protein
      expression levels. Immunohistochemical studies revealed that ERK was strongly
      expressed by blastema cells, mesenchymal cells, and ureteric bud tips in
      nephrogenic zone of embryonic kidney. In neonatal kidney, ERK was more abundant
      in the deep cortex and the medulla corresponding to tubule maturation. p38 and
      MKP-1 were detected uniformly in mesenchymal cells, mesangial cells, and ureteric
      bud epithelia of fetal kidney without an obvious correlation with the occurrence
      of apoptosis. JNK was expressed by tubular cells and podocytes of adult kidney.
      CONCLUSIONS: ERK, p38, and MKP-1 are strongly expressed in developing kidney, and
      JNK is detected predominantly in adult kidney. Both the temporal and spatial
      expression of ERK coincides with the maturation of the kidney.

PMID- 10886547
TI  - Evaluation of the calcium-sensing receptor gene in idiopathic hypercalciuria and
      calcium nephrolithiasis.
AB  - BACKGROUND: Calcium urolithiasis is in part genetically determined and associated
      with idiopathic hypercalciuria. METHODS: We have used a candidate gene approach
      to determine whether the calcium-sensing receptor (CaR) gene is linked to
      idiopathic hypercalciuria and calcium urolithiasis in a cohort of French Canadian
      sibships with multiple affected members (64 sibships from 55 pedigrees yielding
      359 affected sibling pairs with > or =1 stone episode). RESULTS: Using
      nonparametric linkage analysis with various intragenic and flanking markers, we
      showed that the CaR gene could be excluded as a major gene for hypercalciuric
      stone formation. We excluded the CaR (lod score <-2) at lambdas values of 1.5,
      1.68, and 2.6 for sib pairs concordant for at least one stone passage, at least
      two stone passages, and at least one stone passage and calciuria above the 75th
      percentile, respectively. Quantitative trait linkage analyses did not suggest
      that the CaR gene was linked to biochemical markers of idiopathic hypercalciuria.
      CONCLUSIONS: This study shows that genetic variants of the CaR gene are not
      associated with idiopathic hypercalciuria and calcium nephrolithiasis in this
      population of French Canadians.

PMID- 10886548
TI  - Hypoxia and interleukin-1beta stimulate vascular endothelial growth factor
      production in human proximal tubular cells.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) promotes angiogenesis and
      inflammatory reactions. VEGF mRNA is detectable in the proximal tubules of
      inflamed kidneys but not in normals. In other organs VEGF gene expression is
      induced by hypoxia and cytokines such as interleukin 1 (IL-1). To identify the
      cellular mechanisms in control of tubular VEGF production, we studied effects of
      hypoxia and IL-1beta in VEGF mRNA levels, VEGF secretion, and activity of the
      hypoxia-inducible dimeric transcription factor 1 (HIF-1alpha/beta) in human
      proximal tubular epithelial cells (PTECs) in primary culture. METHODS: PTECs were
      grown in monolayers from human kidneys. Hypoxia was induced by incubation at 3%
      O2. VEGF mRNA was quantitated by competitive polymerase chain reaction following
      reverse transcription. VEGF was measured by enzyme-linked immunoassay. HIF-1alpha
      was demonstrated by Western blot analysis and HIF-1 DNA binding by gel shift
      assay. RESULTS: Significant amounts of VEGF mRNA and VEGF protein were measured
      in PTEC extracts and culture media, respectively. Stimulation of VEGF synthesis
      at low O2 tension and following IL-1beta treatment was detectable at the protein
      level only. Nuclear HIF-1alpha protein levels and HIF-1 binding to DNA were also
      increased under these conditions. CONCLUSIONS: PTECs in culture produce VEGF. One
      mechanism of induction appears to be increased DNA binding of HIF-1 to hypoxia
      responsive elements in the VEGF gene promoter. In inflammatory diseases of the
      kidney, tubular cell-derived VEGF may contribute to microvascular leakage and
      monocyte extravasation.

PMID- 10886549
TI  - Mycophenolate mofetil reduces myofibroblast infiltration and collagen III
      deposition in rat remnant kidney.
AB  - BACKGROUND: Myofibroblasts have been shown to play a pivotal role in the
      synthesis of extracellular matrix components in several animal models of renal
      fibrosis. The purpose of the present study was to investigate whether
      mycophenolate mofetil (MMF) reduces interstitial myofibroblast infiltration and
      collagen III deposition in 5/6 nephrectomized rats. METHODS: Forty-five Wistar
      rats underwent 5/6 renal ablation and received by daily oral gavage either
      vehicle (N = 20) or MMF (N = 25) during the 60 days following surgery. Groups of
      five treated and five untreated rats were killed at two, four, and eight weeks
      after subtotal nephrectomy. Four untreated and three treated rats were killed at
      week 12, one month after treatment withdrawal. At the time of sacrifice,
      proteinuria, plasma, and urine creatinine were determined. Immunohistochemistry
      was performed on renal tissue for alpha-smooth muscle actin (alpha-SMA), a
      cytoskeletal marker of myofibroblasts, for type III collagen, and for
      proliferating cell nuclear antigen (PCNA). Moreover, in order to study the in
      vitro effects of MMF on fibroblast proliferation, rat fibroblasts were cultured
      in the presence or absence of mycophenolic acid (MPA). RESULTS: At all periods
      studied, MMF treatment improved renal functional parameters and progressively
      decreased remnant kidney hypertrophy and glomerular volume increment.
      Proliferating cells in renal tubules, interstitium, and glomeruli, as well as
      interstitial myofibroblast infiltration and interstitial type III collagen
      deposition, were also significantly reduced by MMF treatment. In addition, MPA
      exhibited a dose-dependent inhibitory effect on in vitro proliferation of rat
      fibroblasts. CONCLUSION: Reduction of interstitial myofibroblast infiltration may
      be an important event by which MMF significantly prevents renal injury following
      subtotal renal ablation. Thus, our results suggest that MMF could be useful to
      limit the progression of chronic renal disease toward end-stage renal failure.

PMID- 10886550
TI  - Growth hormone receptor abundance in tibial growth plates of uremic rats: GH/IGF
      I treatment.
AB  - BACKGROUND: Children with chronic renal failure (CRF) exhibit growth retardation
      and a disturbed growth hormone/insulin-like growth factor-I (GH/IGF-I) axis.
      Treatment of children with CRF with GH or GH/IGF-I can partially restore linear
      growth. The molecular basis for decreased longitudinal growth is not known but
      may involve an impaired action of GH. METHODS: We used the growth-retarded uremic
      rat model to determine the abundance and distribution of GH receptors (GHRs) in
      the tibial epiphyseal growth plate and the influence of GH, IGF-I, or combined
      GH/IGF-I treatment. Pair-fed rats were used as the control. RESULTS: While all
      treatment regimes increased body length and weight in both rat groups, only
      GH/IGF-I treatment increased the total growth plate width. This involved an
      increase in cell number in the hypertrophic zone, which could also be induced by
      IGF-I alone. Immunohistochemical analysis showed that uremic rats had decreased
      abundance of GHRs in the proliferative zone, and only GH/IGF-I therapy could
      overcome this decrease. These data thus suggest that growth retardation in uremic
      rats is, at least in part, due to a decrease in GHR abundance in chondrocytes of
      the proliferative zone of the tibial growth plate. This decreased GHR abundance
      can be overcome by combined GH/IGF-I therapy, thus enhancing generation and
      proliferation of hypertrophic zone chondrocytes and increasing growth-plate
      width. CONCLUSION: These studies point to a mechanism for the growth retardation
      seen in children with CRF, and suggest that combined GH/IGF-I treatment may
      provide more effective therapy for these patients than GH alone.

PMID- 10886551
TI  - PTHrP enhances the secretory response of PTH to a hypocalcemic stimulus in rat
      parathyroid glands.
AB  - BACKGROUND: The secretion of parathyroid hormone (PTH) from the parathyroid
      glands might be regulated by autocrine/paracrine factors, and a feedback
      regulatory mechanism of PTH on the secretion of PTH has been suggested. Because
      of the existence of a common receptor between PTH and PTH-related peptide
      (PTHrP), the aim of the present study was to examine the possible effects of
      PTHrP 1-40 and 1-86 on PTH secretion in rats. METHODS: In vivo, the effect of
      PTHrP on Ca++-regulated PTH secretion was examined by the induction of
      hypocalcemia and hypercalcemia by an infusion of EGTA and Ca++, with and without
      PTHrP. The eventual effects of PTHrP on the peripheral metabolism of PTH were
      examined by infusion of human PTH (hPTH) with and without PTHrP. hPTH was
      measured by an intact hPTH assay not cross reacting with rat PTH or PTHrP. To
      examine whether near physiological levels of circulating PTH have an
      autoregulatory effect in vivo on PTH secretion from the parathyroid gland, an
      acute reduction of the circulating PTH was induced by an acute unilateral
      parathyroidectomy (UPTX). PTH secretion from the remaining parathyroid gland was
      followed in response to EGTA-induced hypocalcemia. In vitro investigations on the
      effect of PTHrP 1-40 on PTH secretion from whole rat parathyroid glands incubated
      in media containing a calcium concentration of 0.6 or 1.35 mmol/L were performed
      to confirm whether the effect of PTHrP was directly on the gland. The rat PTH
      assay was examined for cross reaction with PTHrP. RESULTS: In vivo, the same rate
      of decrease of plasma Ca++ was induced in the experimental groups. The maximal
      response of PTH to hypocalcemia (218 +/- 16 pg/mL, N = 6) was significantly
      enhanced by PTHrP 1-40 (525 +/- 79 pg/mL, N = 6) and by PTHrP 1-86 (465 +/- 29
      pg/mL, N = 6, P < 0.001). No effect of PTHrP on PTH secretion was found during
      normocalcemia or hypercalcemia. UPTX resulted in a 50% reduction of PTH
      secretion, and no compensatory increase of PTH was observed. PTHrP had no effect
      on the metabolism of PTH. In vitro, low-Ca++-induced PTH secretion was
      significantly augmented by 300% (P < 0.01) when the medium contained PTHrP 1-40.
      PTHrP did not cross react with the PTH assay. CONCLUSIONS: PTHrP significantly
      enhanced the low-Ca++-stimulated PTH secretion in vivo and in vitro. An
      autocrine/paracrine role of PTHrP in the parathyroid glands is suggested. An
      autoregulatory effect of circulating PTH on the PTH secretion from parathyroid
      glands seems unlikely. The "maximal secretory capacity" of the parathyroid glands
      induced by hypocalcemia in vivo and in vitro is not the maximum, as PTH secretion
      can be increased even further, by several-fold.

PMID- 10886552
TI  - Inhibition of nitric oxide synthase ameliorates cellular injury in sickle cell
      mouse kidneys.
AB  - BACKGROUND: In previous studies of transgenic sickle cell mice, increased renal
      expression of inducible nitric oxide synthase (iNOS) and endothelial cell isoform
      of NOS (EcNOS) was found by Western blot and immunohistochemistry. In addition,
      putative evidence of peroxynitrite (ONOO-) formation was found in the form of
      positive immunostaining and immunoblot for nitrotyrosine. Apoptosis was also
      detected by DNA strand breakage and TUNEL assay. The present study was carried
      out to examine the role of NO/ONOO- in mediating renal tubular cell apoptosis in
      sickle cell mouse kidneys. METHODS: Mercaptoethylguanidine (MEG), a compound that
      selectively inhibits iNOS and also is a scavenger of ONOO-, was administered
      intraperitoneally over a five-day period to control and betas mice.
      Immunohistochemistry of iNOS and nitrotyrosine, DNA electrophoresis, ApoTACS
      assay for apoptosis, and Western blot of poly(ADP-ribose) polymerase (PARP) were
      carried out. RESULTS: MEG administration virtually eliminated renal
      immunostaining of iNOS and nitrotyrosine and prevented DNA strand breakage. In
      addition, Western blot analysis of PARP, a nuclear DNA-reparative enzyme
      activated in response to DNA strand breakage, was found to be cleavaged in
      hypoxic betas mice, but was partially protected in MEG-treated betas hypoxic
      mice. Finally, apoptosis was markedly reduced by MEG in betas hypoxic mice.
      CONCLUSIONS: These observations provide evidence that NO and/or ONOO- are
      responsible for initiating cell damage, which leads to apoptosis in sickle cell
      mouse kidneys.

PMID- 10886553
TI  - Combined glomerular deposition of polymeric rat IgA and IgG aggravates renal
      inflammation.
AB  - BACKGROUND: IgA nephropathy (IgAN) is characterized by deposition in the
      glomerular mesangium of IgA together with C3, C5b-9, and properdin. IgG
      deposition as a risk factor in IgAN was recently confirmed by a long-term follow
      up of patients with IgAN. We previously reported on an acute model of IgA
      mediated glomerular inflammation in Wistar rats. METHODS: To investigate the
      effect of the combination of IgA and IgG on glomerular injury, Wistar rats were
      injected with a minimum dose of rat IgG in the presence or absence of a
      subnephritogenic dose of polymeric rat IgA. Subsequently, glomerular complement
      activation, influx of inflammatory cells, proteinuria, and hematuria were
      assessed. RESULTS: Administration of IgG to the rats resulted in maximal
      proteinuria of 20.3 +/- 12.1 mg/24 h on day 2 and an absence of overt glomerular
      inflammation. Administration of polymeric rat IgA antibodies to rats resulted in
      hematuria with a moderate mesangial complement deposition. In the combination
      group, however, glomerular deposition of C5b-9 was dramatically increased. This
      was accompanied by increased proteinuria as compared with rats receiving IgA or
      IgG antibody injections alone on day 7. Microhematuria occurred in rats receiving
      either polymeric rat IgA or IgG alone or the combination. While both rat IgG and
      polymeric IgA induced minor mesangial cell (MC) proliferation and MC lysis, the
      combination resulted in a pronounced, significant increased percentage of
      aneurysm formation on day 7 after injection. CONCLUSIONS: We conclude that in
      this model of IgA-induced glomerulopathy, a selective, complement-dependent
      glomerular inflammation is induced in Wistar rats by glomerular codeposition of
      rat isotypic monoclonal antibodies.

PMID- 10886554
TI  - An anti-CD5 monoclonal antibody ameliorates proteinuria and glomerular lesions in
      rat mesangioproliferative glomerulonephritis.
AB  - BACKGROUND: Increased numbers of lymphocytes have been identified in biopsy
      specimens of human mesangial proliferative glomerulonephritis (GN). However, the
      causal relationship between infiltrating T lymphocytes and mesangial changes in
      mesangial proliferative GN has not been previously evaluated. In this study, we
      elucidated the role of lymphocytes in the development of mesangial proliferative
      GN. METHOD: Immunohistological and flow cytometric analyses as well as a reverse
      transcription-polymerase chain reaction (RT-PCR) studies were performed in
      monoclonal antibody (mAb) 1-22-3-induced Thy 1.1 GN. To elucidate the role of
      these lymphocytes, depletion studies were carried out using anti-CD8 mAb (OX-8),
      which depletes both CD8+ T lymphocytes and natural killer (NK) cells and anti-CD5
      mAb (OX-19), which depletes both CD4+ and CD8+ T lymphocytes. RESULTS:
      Immunofluorescence (IF) studies revealed that NK cells and CD4+ T lymphocytes
      were recruited into glomeruli. Glomerular mRNA expression for interferon-gamma,
      interleukin-2 (IL-2), IL-10, and perforin increased after induction of GN.
      Increased expressions of several chemokines, which have the potential to attract
      lymphocytes, were also detected. Anti-CD8 mAb treatment completely prevented the
      recruitment of NK cells; however, it had no protective effect on proteinuria and
      mesangial injury. By contrast, anti-CD5 mAb treatment suppressed the recruitment
      of CD4+ T lymphocytes into glomeruli and reduced proteinuria (60.4 +/- 25.7 vs.
      120.0 +/- 32.3 mg/day, P < 0.05) and mesangial changes evaluated by total number
      of cells in glomeruli (63.2 +/- 6.0 vs. 81.4 +/- 5.9, P < 0.01) and alpha-smooth
      muscle actin staining score (1.4 +/- 0.2 vs. 2.2 +/- 0. 4, cf2eth P < 0.01) on
      day 14 after induction of GN. mRNA expression for IL-2 was significantly reduced
      by OX-19 treatment. CONCLUSION: T lymphocytes participate in the development of
      mesangial proliferative GN.

PMID- 10886555
TI  - High affinity of anti-GBM antibodies from Goodpasture and transplanted Alport
      patients to alpha3(IV)NC1 collagen.
AB  - BACKGROUND: Anti-glomerular basement membrane (anti-GBM) antibody-mediated
      diseases are characterized by rapidly progressive glomerulonephritis (RPGN) that
      often results in irreversible loss of renal function and renal failure. Although
      many factors contribute to the fulminant nature and treatment resistance of this
      disease, we questioned whether high affinity autoantibody-alpha3(IV) collagen
      interactions lead to persistent antibody deposition, thereby perpetuating
      inflammation. To address this hypothesis, the binding kinetics of human anti-GBM
      antibodies (Ab) to alpha3(IV)NC1 were evaluated using an optical biosensor
      interaction analysis. METHODS: Polyclonal anti-GBM Abs were purified by
      alpha3(IV)NC1 affinity chromatography from the sera of patients with anti-GBM AB
      mediated diseases, including individuals with Goodpasture syndrome (GS),
      idiopathic RPGN (N = 7), and Alport syndrome (AL) following kidney
      transplantation (N = 4). The affinity-binding characteristics of the
      autoantibodies were determined using a biosensor analysis system, with
      immobilized bovine alpha3(IV)NC1 dimers. RESULTS: All of the autoantibody
      preparations bound to alpha3(IV)NC1, whereas none bound to alpha1(IV)NC1
      (control). Purified, normal serum IgG did not bind to either antigen. Estimated
      dissociation constants (Kd) for the purified autoantibodies were 1.39E-04 +/-
      7.30E-05 s-l (GS) and 8. 90E-05 +/- 2.80E-05 s-l (AL). Their estimated
      association constants (Ka) were 2.67E+04 +/- 1.8E+04 (M-ls-l) and 2.76E+04 +/- 1.
      70E+04(M-ls-l) for GS and AL patients, respectively. By comparison with other Ab
      interactions, these Abs demonstrated high affinity, with relatively high on
      (binding) rates and slow off (dissociation) rates. CONCLUSIONS: The results
      suggest that anti-GBM Abs bind rapidly and remain tightly bound to the GBM in
      vivo. This property likely contributes to both the fulminant nature of this
      disease and its resistance to therapy, because persistent glomerular Ab
      deposition has the potential to produce continuous inflammation, despite removal
      of circulating Abs and adequate immunosuppression.

PMID- 10886556
TI  - Cyclosporine induces different responses in human epithelial, endothelial and
      fibroblast cell cultures.
AB  - BACKGROUND: Nephrotoxicity, accelerated atherosclerosis, and graft vascular
      disease are common complications of cyclosporine long-term treatment
      characterized by a wide disruption of organ architecture with increased
      interstitial areas and accumulation of extracellular matrix (ECM). How
      cyclosporine induces these changes is not clear, but it is conceivable that they
      are the sum of changes induced at the cell level. METHODS: We studied the effects
      of cyclosporine on human endothelial (HEC), epithelial (HK-2), and fibroblast
      (MRC5) cells. Cell proliferation was evaluated by cell counting, apoptosis and
      collagen production by enzyme-linked immunosorbent assay, and nitric oxide by
      measuring the concentration of nitrite/nitrate in the cell supernatant. (alpha1)I
      and (alpha2)IV collagen, matrix metalloprotease-9 (MMP9), and tissue inhibitors
      of metalloprotease-1 (TIMP-1) mRNA levels were measured by reverse transcription
      polymerase chain reaction. Proteolytic activity was evaluated by zymography.
      RESULTS: Cyclosporine showed a marked antiproliferative and proapoptotic effect
      on endothelial and epithelial cells. Fibroblast growth was not affected by
      cyclosporine. Nitric oxide was up-regulated by cyclosporine in epithelial cells
      and fibroblasts but not in endothelial cells. (alpha1)I and (alpha2)IV collagen
      synthesis was increased in cyclosporine-treated endothelial and epithelial cells,
      respectively. Proteolytic activity was increased in endothelial and epithelial
      cells. TIMP-1 mRNA was up-regulated by cyclosporine in fibroblasts. CONCLUSIONS:
      Our results demonstrate that cyclosporine exhibits an antiproliferative effect on
      endothelial and epithelial cells. This effect is associated with induction of
      apoptosis probably via nitric oxide up-regulation in epithelial cell cultures.
      Cyclosporine treatment induces ECM accumulation by increasing collagen synthesis
      in endothelial and epithelial cells and reducing its degradation by up-regulating
      TIMP-1 expression in fibroblasts. We conclude that cyclosporine affects cell
      types differently and that the disruption of organ architecture is the result of
      multiple effects at the cell level.

PMID- 10886557
TI  - Transforming growth factor-beta1 increases albumin permeability of isolated rat
      glomeruli via hydroxyl radicals.
AB  - BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) is a multifunctional
      cytokine. Glomerular cells and tubular epithelial cells secrete and respond to
      TGF-beta1. A close association between elevated levels of TGF-beta1 and the
      development of glomerulonephritis, glomerulosclerosis, and tubular hypertrophy
      has been documented. The role of TGF-beta1 in proteinuria is not well understood.
      METHODS: Isolated rat glomeruli were incubated in medium alone or with TGF-beta1
      (1 to 10 ng/mL) and TGF-beta1 + 200 U/mL of superoxide dismutase (SOD) or 1
      mmol/L of dimethylthiourea (DMTU) scavengers of superoxide and hydroxyl radicals,
      respectively, for up to 60 minutes at 37 degrees C. Glomerular albumin
      permeability (Palb) was calculated from the volumetric response of glomeruli to
      an oncotic gradient using videomicroscopy. RESULTS: One or 2.5 ng/mL of TGF-beta1
      had no effect on Palb (0.18 +/- 0.08, N = 17; 0.18 +/- 0. 079, N = 20 vs. control
      0.00 +/- 0.06, N = 25), whereas 5 or 10 ng/mL of TGF-beta1 caused a significant
      increase in Palb (0.31 +/- 0. 09, N = 20; 0.33 +/- 0.06, N = 23) within 15
      minutes. The effect of 10 ng/mL of TGF-beta1 on Palb increased further after 30,
      45, or 60 minutes of incubation (0.43 +/- 0.06, N = 24; 0.53 +/- 0.06, N = 25;
      0.74 +/- 0.075, N = 21). The TGF-beta1-induced increase in Palb (0. 75 +/- 0.065,
      N = 15) was blocked by SOD (0.07 +/- 0.14 N = 15) or by DMTU (0.04 +/- 0.13, N =
      15). Incubation of glomeruli with the carrier medium (4N HCl) in which TGF-beta1
      is dissolved and SOD or DMTU alone did not affect Palb. CONCLUSION: Elevated
      levels of TGF-beta1 derived from glomerular or extraglomerular sources are
      capable of increasing glomerular Palb via superoxide and hydroxyl radicals and
      may lead to proteinuria in vivo.

PMID- 10886558
TI  - Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies.
AB  - BACKGROUND: Mature podocytes are growth-arrested because of the expression of
      cyclin-dependent kinase inhibitors. Under pathological conditions, podocytes may
      undergo mitosis, but not cell division. Exceptions to this rule are collapsing
      glomerulopathies (CGs), including HIV-associated nephropathy (HIVAN) and
      idiopathic CG, where podocytes undergo a dysregulation of their differentiated
      phenotype and proliferate. METHODS: To shed light on the mechanism underlying
      podocyte proliferation in CG, we analyzed the expression of the proliferation
      marker Ki-67, cyclins (A, D1), cyclin-dependent kinase inhibitors (p27, p57), and
      podocyte differentiation marker synaptopodin in eight cases of HIVAN and two
      cases of idiopathic CG. Normal fetal and adult kidneys served as controls.
      RESULTS: Both HIVAN and idiopathic CG showed a marked reduction in the expression
      of p27, p57, and cyclin D1 (absent in 69, 62, and 80% of all glomeruli,
      respectively). Cyclin A and Ki-67 were expressed in 11 and 29% of all glomeruli.
      Moreover, there was partial loss of synaptopodin and cyclin D1 expression in
      nonaffected glomeruli. CONCLUSIONS: The loss of p27 and p57 leading to expression
      of cyclin A may account for the activation of podocyte proliferation in CG.
      Furthermore, the loss of cyclin D1 from histologically normal glomeruli suggests
      a possible role of cyclin D1 in mediating the dysregulation of the podocyte cell
      cycle in CG. These novel findings offer insight into the molecular regulation of
      mature podocyte differentiation. Podocyte proliferation in CG provides evidence
      in support of a previously underestimated plasticity of mature podocytes.

PMID- 10886560
TI  - Effects of ACE inhibition and bradykinin antagonism on cardiovascular changes in
      uremic rats.
AB  - BACKGROUND: Cardiovascular death continues to be a major problem in renal
      failure. Structural abnormalities of the heart and the vasculature contribute to
      the increased cardiovascular risk. They are ameliorated by angiotensin-converting
      enzyme (ACE) inhibitors, but because of the nonspecifity of ACE inhibition, it is
      uncertain whether the beneficial effect is mediated by interfering with
      angiotensin II (Ang II) or by modulating other effector systems, for example,
      bradykinin. METHODS: To assess a potential role of bradykinin, subtotally
      nephrectomized Sprague-Dawley rats (SNX) received either the ACE inhibitor
      Ramipril (Rami, 0.2 mg/kg body weight p.o.), the specific B2 bradykinin receptor
      antagonist Hoe140 (0.2 mg/kg body weight, s.c.), or a combination of both, and
      were compared to sham-operated controls. To separately assess the effect of
      Ramipril on development and reversal of structural abnormalities, animals were
      either treated from the third day after SNX or from the fourth week after SNX
      onward (0.01 mg/kg body weight, p.o.). RESULTS: Heart and aorta were evaluated by
      morphometric and stereologic techniques. The weight of the perfused left
      ventricle, as an index of cardiac hypertrophy, was significantly higher in
      untreated SNX. While it was significantly lower in animals with early and late
      Ramipril treatment, the beneficial effect was completely antagonized by Hoe140.
      The wall-to-lumen ratio of intramyocardial arterioles was significantly higher in
      untreated SNX compared with controls, but failed to be modified by administration
      of either Ramipril or Hoe140. In the heart, the intercapillary distance was
      significantly higher in SNX, but it was not lowered by either early or late
      Ramipril or Hoe140 treatment. Treatment of SNX with Hoe140 alone, however,
      resulted in a marked further increase in intercapillary distance. The wall
      thickness of the aorta was significantly higher in SNX than in controls; early
      and late Ramipril treatment prevented such increase, and this effect was
      antagonized by Hoe140. CONCLUSION: These findings illustrate that bradykinin
      plays an important role for the beneficial effect of Ramipril in preventing (and
      potentially reversing) abnormal cardiovascular structure in uremic hypertensive
      rats.

PMID- 10886559
TI  - Angiotensin II induces renal oxidant stress in vivo and heme oxygenase-1 in vivo
      and in vitro.
AB  - BACKGROUND: Angiotensin II is strongly incriminated in progressive renal injury.
      There is recent evidence that angiotensin II induces oxidative stress in vitro.
      We examined the capacity of angiotensin II to induce oxidative stress in vivo and
      the functional significance of such stress. The capacity of angiotensin II to
      induce the oxidant-sensitive gene heme oxygenase (HO) in vivo and in vitro was
      also examined. METHODS: Angiotensin II was administered via mini-osmotic pumps to
      rats maintained on standard diets. Indices of oxidative stress, including
      thiobarbituric acid reactive substance, carbonyl protein content, and HO
      activity, were determined. Indices of oxidative stress and functional markers
      were also determined in the DOCA salt model. The effect of angiotensin II was
      studied in rats maintained on antioxidant-deficient diets so as to examine the
      functional significance of oxidative stress induced by angiotensin II. We also
      explored the inductive effect of angiotensin II on HO in vivo and whether such
      actions occur in vitro. RESULTS: Angiotensin II administered in vivo increased
      kidney content of thiobarbituric acid reactive substances protein carbonyl
      content, and HO activity. These indices were not present in the kidney of rats
      treated with DOCA salt for three weeks. Such oxidative stress was functionally
      significant, since the administration of angiotensin II to rats maintained on a
      prooxidant diet demonstrated increased proteinuria and decreased creatinine
      clearance. The stimulatory effect on HO activity was due to induction of HO-1
      mRNA, with HO-2 mRNA remaining unchanged. Expression of HO-1 was localized to the
      renal proximal tubules in vivo. We also demonstrate that angiotensin II at
      concentrations of 10-8 and 10-7 mol/L induces expression of HO-1 mRNA in LLC-PK1
      cells. CONCLUSIONS: Angiotensin II induces oxidative stress in vivo, which
      contributes to renal injury. This study also demonstrates that angiotensin II
      induces renal HO activity caused by up-regulation of HO-1 in renal proximal
      tubules. Finally, angiotensin II directly induces HO-1 in renal proximal tubular
      epithelial cells in vitro.

PMID- 10886561
TI  - G1 kinases and transforming growth factor-beta signaling are associated with a
      growth pattern switch in diabetes-induced renal growth.
AB  - BACKGROUND: Diabetes mellitus-induced nephromegaly is thought to involve both
      hyperplastic and hypertrophic proximal tubule cell growth. The temporal
      relationship between these growth patterns and the mechanisms that mediate them
      are unknown. METHODS: Renal growth was assayed in isolated renal proximal tubules
      harvested from diabetic rats. Diabetes mellitus was induced by streptozotocin.
      RESULTS: Following the induction of a diabetic state, there was a progressive
      increase in the kidney:body weight ratio. This was associated with an increase in
      5-bromo-2-deoxyuridine incorporation (marker for hyperplastic cell growth) at day
      2, which returned to baselines levels by day 4, and an increase in the
      protein:DNA ratio (marker for hypertrophic cell growth), which was clearly
      evident by day 10. Thus, diabetes-induced proximal tubule growth involved an
      initial hyperplastic, followed by a hypertrophic, growth period. During the
      hyperplastic growth period, both cdk4/cyclin D (cyclin D) and cdk2/cyclin E
      (cyclin E) kinase activities were increased. The switch between the growth
      periods was associated with continued activation of cyclin D, but inhibition of
      cyclin E kinase. The reduction in cyclin E kinase activity correlated with a
      reduction in cdk2/cyclin E complex abundance and an increased abundance of cyclin
      kinase inhibitors in cdk2/cyclin E complexes that did form. Also associated with
      the switch in growth patterns was a change in transforming growth factor-beta
      (TGF-beta) receptor expression. During the hyperplastic growth period, TGF-beta
      receptor II expression was decreased, while during the hypertrophic growth
      period, there was both a return of receptor II expression to baseline levels and
      increased expression of receptor I. Consistent with an increase in TGF-beta
      signaling during hypertrophy, there was an increase in Smad 2/3 protein
      expression and an increase in the abundance of Smad 2/4 complexes. CONCLUSIONS:
      Diabetes-induced proximal tubule growth involves an initial hyperplastic growth
      period that switches to a hypertrophic growth period within a couple of days. The
      pattern of G1 kinase activity associated with the growth pattern switch
      demonstrates that the hypertrophy is mediated by a cell cycle-dependent
      mechanism. Regulation of TGF-beta receptor expression and signaling activity
      through the Smad protein cascade possibly plays a role in the growth pattern
      switch.

PMID- 10886562
TI  - HIV-1 induces renal epithelial dedifferentiation in a transgenic model of HIV
      associated nephropathy.
AB  - BACKGROUND: Human immunodeficiency virus-associated nephropathy (HIVAN) is the
      most common cause of renal failure in HIV-1-seropositive patients. Recent studies
      using an HIV-1 transgenic mouse model have demonstrated that expression of HIV-1
      in the kidney is required for the development of HIVAN. What has remained
      unclear, however, is the renal cell type responsible for pathogenesis and the
      essential pathological process. METHODS: To address these issues, we used a
      transgenic murine model of HIVAN. We identified the cell types in kidney in which
      HIV transgene expression occurs using in situ hybridization. We evaluated
      evidence of proliferation by immunocytochemical analysis using an antibody to Ki
      67 and cell type-specific markers, including WT-1, synaptopodin, Na+,K+-ATPase,
      adducin, and desmin. TUNEL assay was used to evaluate apoptosis. RESULTS: We
      found that glomerular and tubular epithelial cells express the HIV-1 transgene
      early in the disease process when renal architecture is well preserved. Transgene
      expression is lost, however, in tubular epithelial cells when they lose their
      differentiated cuboidal phenotype. In glomerular epithelial cells,
      dedifferentiation occurs with reduced expression of WT-1 and synaptopodin, in
      association with activation of desmin expression. Tubular microcysts also form
      with mislocalization of Na+,K+-ATPase expression to the lateral and apical
      cellular membranes. CONCLUSIONS: These studies support the hypothesis that the
      glomerular and renal epithelial cells are the primary targets of HIV-1
      pathogenesis in the kidney. The essential pathologic process is dysregulation of
      the epithelial cell cycle with increased proliferation, apoptosis, cellular
      dedifferentiation, and altered cellular polarity.

PMID- 10886563
TI  - MCP-1 and EGF renal expression and urine excretion in human congenital
      obstructive nephropathy.
AB  - BACKGROUND: Obstructive nephropathy is characterized at the histologic level by
      tubular atrophy and interstitial monocyte infiltration. The molecular mechanisms
      underlying these histologic changes are still poorly defined. Epidermal growth
      factor (EGF) produced by tubular cells seems to play a pivotal role in the
      modulation of tubular cell growth, while monocyte chemotactic peptide-1 (MCP-1)
      is a powerful and specific chemotactic and activating factor for monocytes.
      METHODS: Twenty-four patients with congenital ureteropelvic junction obstruction
      [UPJO; 10 with recurrent urinary tract infection (UTI) and 10 with no UTI] and 15
      healthy children were studied. Diagnosis was made by renal ultrasound,
      intravenous pielography, and MAG3 scan. Urinary samples were collected before and
      after surgery. In 10 patients, urine was also collected directly from the
      affected pelvis at the time of surgery. Urinary EGF and MCP-1 levels were
      measured by enzyme-linked immunosorbent assay. MCP-1 and EGF gene expression were
      evaluated by in situ hybridization in 15 biopsies from congenital UPJO and in 10
      normal kidneys. RESULTS: In normal kidneys, there was a high expression of EGF
      mRNA, whereas MCP-1 mRNA was undetectable. MCP-1 gene expression was strikingly
      increased at the tubulointerstitial level in UPJO biopsies compared with controls
      and was directly correlated with the extent of monocyte infiltration. In
      addition, UPJO kidney sections showed a marked reduction in EGF gene expression
      that was directly correlated with the degree of tubular damage. EGF urine
      concentration was significantly reduced in UPJO when compared with control and
      directly correlated with its renal gene expression. On the other hand, the MCP-1
      urine concentration was strikingly increased in UPJO patients. It is noteworthy
      that a significant and inverse correlation was observed between the MCP-1
      concentration in the urine collected from the obstructed pelvis and the MAG3
      clearance of the obstructed kidney (r = -0.76). The presence of recurrent UTI was
      associated with a significantly higher MCP-1 excretion and a slight reduction in
      EGF urine concentration. The surgical correction of UPJO was followed by an
      improvement of renal function together with a significant reduction in MCP-1
      excretion and a marked increase in EGF urine concentrations. Interestingly, EGF
      urine concentration measured before surgery was significantly correlated with the
      difference between the MAG3 clearance of the obstructed kidney before and after
      surgery. CONCLUSIONS: MCP-1 and EGF seem to be involved in the pathogenesis of
      tubulointerstitial damage in congenital obstructive nephropathy, and their urine
      excretion may represent a powerful prognostic marker in this form of renal
      disease.

PMID- 10886564
TI  - Plasma membrane cholesterol: a critical determinant of cellular energetics and
      tubular resistance to attack.
AB  - BACKGROUND: Cholesterol is a major component of plasma membranes, forming
      membrane microdomains ("rafts" or "caveolae") via hydrophobic interactions with
      sphingolipids. We have recently demonstrated that tubule cholesterol levels rise
      by 18 hours following diverse forms of injury, and this change helps to protect
      kidneys from further damage (so-called acquired cytoresistance). The present
      study was undertaken to better define the effects of membrane
      cholesterol/microdomains on tubule homeostasis and cell susceptibility to
      superimposed attack. METHODS: Plasma membrane cholesterol was perturbed in normal
      mouse proximal tubular segments with either cholesterol esterase (CE) or
      cholesterol oxidase (CO). Alternatively, cholesterol-sphingomyelin complexes were
      altered by sphingomyelinase (SMase) treatment. Changes in cell energetics
      (ATP/ADP ratios + ouabain), viability [lactate dehydrogenase (LDH) release],
      phospholipid profiles, and susceptibility to injury (Fe-induced oxidant stress,
      PLA2, Ca2+ ionophore) were determined. The impacts of selected cytoprotectants
      were also assessed. RESULTS: Within 15 minutes, CE and CO each induced
      approximately 90% ATP/ADP ratio suppressions. These were seen prior to lethal
      cell injury (LDH release), and it was ouabain resistant (suggesting decreased ATP
      production, not increased consumption). SMase also depressed ATP without inducing
      cell death. After 45 minutes, CE and CO each caused marked cytotoxicity (up to
      70% LDH release). However, different injury mechanisms were operative since (1)
      CE, but not CO, toxicity significantly altered cell phospholipid profiles, and
      (2) 2 mmol/L glycine completely blocked CE- but not CO-mediated cell death.
      Antioxidants also failed to attenuate CO cytotoxicity. Disturbing
      cholesterol/microdomains with a sublytic CE dose dramatically increased tubule
      susceptibility to Fe-mediated oxidative stress and Ca2+ overload, but not PLA2
      mediated damage. CONCLUSION: Intact plasma membrane cholesterol/microdomains are
      critical for maintaining cell viability both under basal conditions and during
      superimposed attack. When perturbed, complex injury pathways can be impacted,
      with potential implications for both the induction of acute tubular damage and
      the emergence of the postinjury cytoresistance state.

PMID- 10886565
TI  - Chronic metabolic acidosis increases NaDC-1 mRNA and protein abundance in rat
      kidney.
AB  - BACKGROUND: Chronic metabolic acidosis increases, while alkali feeding inhibits,
      proximal tubule citrate absorption. The activity of the apical membrane
      Na+/citrate cotransporter is increased in metabolic acidosis, but is not altered
      by alkali feeding. METHODS: Renal cortical mRNA and brush border membrane protein
      abundances of sodium/dicarboxylate-1 (NaDC-1), the apical membrane Na+/citrate
      transporter, were measured. RESULTS: By immunohistochemistry, NaDC-1 was
      localized to the apical membrane of the proximal tubule. Chronic metabolic
      acidosis caused an increase in NaDC-1 protein abundance that was maximal in the
      S2 segment and that increased with time. Metabolic acidosis also increased NaDC-1
      mRNA abundance, but this was first seen at three hours and correlated with the
      severity of the metabolic acidosis. Alkali feeding had no effect on NaDC-1
      protein or mRNA abundance. CONCLUSIONS: Chronic metabolic acidosis increases
      renal cortical NaDC-1 mRNA abundance and apical membrane NaDC-1 protein
      abundance, while alkali feeding is without effect on NaDC-1.

PMID- 10886566
TI  - Dysregulation of renal aquaporins and Na-Cl cotransporter in CCl4-induced
      cirrhosis.
AB  - BACKGROUND: Severe hepatic cirrhosis is associated with abnormal renal water
      retention. METHODS: Semiquantitative immunoblotting was employed to investigate
      the abundance of the major renal aquaporins (water channels) and sodium-dependent
      cotransporters in kidneys from control rats and rats with cirrhosis secondary to
      chronic CCl4 inhalation. RESULTS: The cirrhotic rats had ascites and manifested a
      water excretion defect detected by a standard water-loading test. The abundance
      of aquaporin-1 (the major aquaporin in the proximal tubule) was increased, an
      effect markedly accentuated in high-density membrane fractions prepared by
      differential centrifugation. Differential centrifugation studies demonstrated a
      redistribution of aquaporin-2 from high-density to low-density membranes,
      compatible with increased trafficking of aquaporin-2 to the plasma membrane. The
      abundance of aquaporin-3, but not aquaporin-2, was increased in collecting ducts
      of rats with CCl4-induced cirrhosis. The Na-K-2Cl cotransporter of the thick
      ascending limb showed no change in abundance. However, the abundance of the
      thiazide-sensitive Na-Cl cotransporter of the distal convoluted tubule was
      markedly suppressed in cirrhotic rats, possibly contributing to a defect in
      urinary dilution. CONCLUSIONS: In this model of cirrhosis, the development of a
      defect in urinary dilution may be multifactorial, with contributions from at
      least four abnormalities in transporter regulation: (1) an increase in the renal
      abundance of aquaporin-1, (2) a cellular redistribution of aquaporin-2 in the
      collecting duct compatible with trafficking to the plasma membrane without an
      increase in total cellular aquaporin-2, (3) an increase in the renal abundance of
      aquaporin-3, and (4) a decrease in the abundance of the thiazide-sensitive
      cotransporter of the distal convoluted tubule.

PMID- 10886567
TI  - Red cell Na+/Li+ countertransport and Na+/H+ exchanger isoforms in human proximal
      tubules.
AB  - BACKGROUND: Increased activity of the Na+/Li+ countertransporter (SLC) is a well
      recognized intermediate phenotype of hypertension and diabetic nephropathy and
      may indicate a predisposition to hypertension. Previous work has attempted to
      link this membrane transport marker to altered Na+ reabsorption in the proximal
      tubule. Since the Na+/H+ exchanger (NHE) isoforms 1 and 3 are expressed in the
      basolateral and apical membranes of the proximal tubule, respectively, we
      investigated the relationship between these transport proteins and red cell SLC
      to examine whether the peripheral blood transport phenotype is associated with
      altered levels of transport proteins in the proximal tubule. METHODS: Proximal
      tubules were prepared from human nephrectomy specimens. NHE-1 and NHE-3 were
      detected on Western blots by specific antibodies. Red cell SLC was also measured.
      RESULTS: Both NHE-1 and NHE-3 proteins were demonstrated, with molecular weights
      of 97 and 85 kD, respectively. SLC was very strongly correlated with the level of
      NHE-3 protein (r = 0.78, P < 0.001) and was negatively related to NHE-1 protein
      (r = -0.32). In multiple regression analysis, only NHE-3 and NHE-1 protein levels
      were significant predictors of red cell SLC, accounting for up to about 70% of
      the variance of this parameter. CONCLUSIONS: We conclude that red cell SLC may be
      a marker of increased NHE-3 protein expression in the proximal tubule, which may
      account for the blunted pressure natriuresis and predisposition to hypertension.

PMID- 10886568
TI  - Alterations of protein metabolism by metabolic acidosis in children with chronic
      renal failure.
AB  - BACKGROUND: Several reports suggest that metabolic acidosis may induce
      significant alterations in protein metabolism and that its outbreak may even
      result in growth retardation in children with chronic renal failure (CRF).
      However, the effects of metabolic acidosis on protein metabolism kinetics have
      never been investigated in these settings. METHODS: Postabsorptive leucine
      metabolism, a marker of whole-body protein metabolism, was measured by using a
      primed, continuous intravenous infusion of L-[1-13C]leucine in 10 CRF children
      who were one to four years old. RESULTS: Interindividual values of whole-body
      protein turnover exhibited a very large range, which was mainly accounted for by
      acidotic status (plasma HCO3-) and body composition [fat-free mass (FFM)]. After
      correction for differences in FFM, plasma HCO3- was highly correlated with
      protein breakdown (R2 = 0.65, P < 0.001), so that CRF children were divided in
      two groups according to their acid-base status: Group A had a mean plasma HCO3-
      level of 15.8 +/- 1.5 mmol. L-1 (mean +/- SD, N = 5), whereas group B had near
      normal values (HCO3-, 22.6 +/- 3.0 mmol. L-1, N = 5). The leucine rate of
      appearance from protein breakdown was markedly higher in group A than in group B
      (4.15 +/- 1.43 vs. 2.46 +/- 0.47 micromol. kg-1. min-1, respectively, P < 0.05),
      and the net leucine balance tended to be more negative in group A (-0.73 +/- 0.34
      vs. -0.44 +/- 0.26 micromol. kg-1. min-1, respectively). CONCLUSIONS: Metabolic
      acidosis in children with CRF results in an excessive catabolic state, suggesting
      that acidosis-related protein wasting could contribute to growth retardation.

PMID- 10886569
TI  - Long-term renal effects of unilateral ureteral obstruction and the role of
      endothelin.
AB  - BACKGROUND: Angiotensin II (Ang II) and endothelin (ET) are involved in the
      alteration of renal function in unilateral ureteral obstruction (UUO). The renal
      response to Ang II following the reversal of a 24-hour UUO and the effect of ET
      blockade by bosentan during the time of obstruction were investigated. METHODS:
      Following blockade of the endogenous production of Ang II by captopril, the renal
      response to Ang II was studied in rats 15 to 18 days after a 24-hour UUO (N = 10)
      or a sham operation (N = 9) both with (N = 10) and without (N = 8) bosentan
      treatment in the periobstruction period. Similar studies were performed in
      another group (N = 9) two months following the reversal of obstruction. RESULTS:
      In the sham-operated group, Ang II reduced renal blood flow (RBF) by 42 +/- 9% (P
      < 0.01), glomerular filtration rate (GFR) by 30 +/- 8% (P < 0.01), urine volume
      (UV) by 44 +/- 9% (P < 0.001), and absolute (UNaV) and fractional sodium
      excretion (FENa) by 52 +/- 9% (P < 0.001) and 33 +/- 9% (P = 0.054),
      respectively. In the previously obstructed kidney, Ang II did not change RBF but
      increased GFR by 106 +/- 40% (P < 0.01), UV by 75 +/- 21% (P < 0.001), UNaV by
      190 +/- 60% (P < 0.001), and FENa by 40 +/- 13% (P < 0.05). Bosentan treatment in
      the obstructed group prevented these Ang II-induced effects and did not have any
      effect on the sham-operated kidney. Two months following reversal of the
      obstruction, the response of the kidney was similar to that of the control
      kidney. CONCLUSION: Twenty-four-hour UUO results in a temporary abnormality in
      the renal response to Ang II, which is due, in part, to the actions of ET at the
      time of obstruction.

PMID- 10886571
TI  - Inadequate diagnosis and therapy of arterial hypertension as causes of left
      ventricular hypertrophy in uremic dialysis patients.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is highly prevalent in the
      dialyzed population, possibly because of inadequate diagnosis and therapy of
      arterial hypertension. The purpose of this study was to ascertain the adequacy of
      our approach in correctly identifying and treating arterial hypertension in our
      dialysis center. METHODS: Fifty-five dialyzed uremics were studied by continuous
      ambulatory blood pressure (BP) monitoring, which started before a single
      hemodialysis (HD) session, continued for 24 hours after HD ended, and was
      repeated for 15 minutes before the beginning of the next HD. Clinical pre-HD and
      post-HD routine BP measurements taken the month preceding BP monitoring were
      retrieved, and echocardiography was performed. RESULTS: LVH was present in 46 out
      of 55 patients, and clinical pre-HD arterial hypertension was present in 36 out
      of 55. There were discrepancies between clinical and monitored BPs, mostly
      concerning diastolic pre-HD BP since BP readings were lower than monitored BP
      records (P < 0.0002). Although both clinical and monitored BPs bore strong direct
      correlations with the left ventricular mass (LVM), the closest correlations were
      those for monitored BP. Four groups of patients were identified by BP monitoring:
      group A (N = 14), with persistently normal BP, and group D (N = 13), with
      persistently supranormal BP levels. There were also two other groups (group B, N
      = 19; and group C, N = 9), whose BP values were high before HD, normalized after
      HD, and then increased again either soon after HD (group C) or later on following
      HD (group B). Monthly averaged clinical pre-HD mean BP values differed
      significantly among the four groups [91 +/- 10 (SD) mm Hg in group A, 101 +/- 7
      in group B, 106 +/- 6 in group C, and 106 +/- 7 in group D; P < 0.0001, analysis
      of variance], as did their corresponding LVMs [132 +/- 27 g/m2 body surface area
      (BSA), 156 +/- 26, 201 +/- 51, and 200 +/- 36; P < 0.0001]. There were also
      differences in dialytic age, which was significantly longer in group A patients
      (109 +/- 54 months), who also tended to have higher, although not significantly
      higher, Kt/V(urea) values. No differences, however, were detected among the
      groups as far as type, dosages, and number of antihypertensive drugs given to
      each individual patient. CONCLUSIONS: The high prevalence of LVH in the dialysis
      population might be the result of inadequate diagnosis and therapy of arterial
      hypertension. Arterial hypertension, in fact, was insufficiently treated in our
      dialysis center, since patients with varying degrees of severity of both arterial
      hypertension and LVH were kept on antihypertensive therapy of similar strength.
      Undertreatment may have resulted from not having recognized and/or from having
      underestimated the severity of arterial hypertension since some clinical BPs were
      measured incorrectly. Reluctance to use more aggressive antihypertensive therapy
      might also result from the deceptive feeling of "normalized" BP that one has
      following volume unloading with dialysis. This causes both the BP to run out of
      control between dialyses and LVH to worsen.

PMID- 10886570
TI  - Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type
      1 receptor in vivo.
AB  - BACKGROUND: The fibrinolytic system plays an important role in degrading fibrin
      rich thrombi and in vascular and tissue remodeling. Elevated levels of
      plasminogen activator inhibitor-1 (PAI-1) can reduce the efficiency of the
      endogenous fibrinolytic system. Angiotensin (Ang) has been shown to regulate PAI
      1 expression via the Ang type 1 (AT1) receptor in some tissues and via the AT4
      receptor in cultured endothelium. The purpose of this study was to examine the
      tissue-specific pattern of PAI-1 expression in response to infusion of Ang II in
      vivo. METHODS: Adult male Sprague-Dawley rats (N = 5 in each group) were treated
      with four hours of intravenous infusions of Ang II or vehicle control while mean
      arterial pressure (MAP) was monitored: group 1, 600 ng/kg/min Ang II; group 2,
      Ang II + 10 mg/kg of the AT1 receptor antagonist (AT1RA) L158-809 q2 hour; group
      3, Ang II + 0.01 to 0.1 mg/kg hydralazine as required to maintain normal blood
      pressure; and group 4, saline-infused controls. After infusion, tissue was
      harvested for Northern blotting, immunohistochemical analysis, and in situ
      hybridization. RESULTS: In group 1, Ang II infusion increased MAP from 105 +/- 8
      to 160 +/- 9 mm Hg (mean +/- SE, P < 0. 01). Ang II induced increased expression
      of PAI-1 mRNA in all tissues examined from 5.1-fold in the heart, 9.7-fold in the
      kidney, 10.0-fold in the aorta, and up to 30.0-fold in the liver (all P < 0. 01
      vs. control). While both AT1RA (group 3) and hydralazine (group 4) prevented Ang
      II-induced elevation in blood pressure, the Ang II-dependent expression of PAI-1
      mRNA was reduced by only AT1 receptor blockade. CONCLUSIONS: We conclude that in
      the rat, PAI-1 is induced in a variety of tissues by Ang II directly through the
      AT1 receptor, independent of its effects on blood pressure.

PMID- 10886572
TI  - Erythropoietin regulates vascular smooth muscle cell apoptosis by a
      phosphatidylinositol 3 kinase-dependent pathway.
AB  - BACKGROUND: Recent studies have shown that several cytokines could induce
      apoptosis in vascular smooth muscle cells (VSMCs) via the induction of nitric
      oxide (NO). In the present study, we explored whether human recombinant
      erythropoietin (rHuEPO) has a modulatory effect of apoptosis on interleukin-1beta
      (IL-1beta) or NO donor sodium nitroprusside (SNP)-induced apoptosis in rat
      cultured VSMCs. METHODS: The quantitation of apoptosis among VSMCs was assessed
      by nuclear morphological analysis with fluorescent DNA-binding dye Hoechst 33258.
      Apoptotic changes were also confirmed by the detection of DNA fragmentation. The
      expression of EPO receptor (EpoR), cellular protein tyrosine phosphorylation,
      including EpoR and Janus kinase (JAK) 2, and the association of p85 subunit of
      phosphatidylinositol 3 kinase (PI3-kinase) to tyrosine-phosphorylated proteins,
      including EpoR, were explored by using Western blotting analysis combined in part
      with immunoprecipitation. RESULTS: rHuEPO inhibited the apoptosis induced by IL
      1beta or SNP in a dose- and time-dependent manner. The anti-apoptotic effects of
      rHuEPO were diminished in the presence of a tyrosine kinase (TK) inhibitor
      genistein or anti-EpoR antibody. After stimulation with rHuEPO, EpoR and JAK 2
      were tyrosine phosphorylated, and p85 subunits were associated with EpoR. Also,
      rHuEPO induced phosphorylation of Akt through a PI3-kinase-dependent pathway. The
      phosphorylation of Akt and the anti-apoptotic effects of rHuEPO were diminished
      in the presence of a PI3-kinase inhibitor, wortmannin. CONCLUSION: Our present
      study demonstrates that rHuEPO inhibites IL-1beta or SNP-induced VSMC apoptosis.
      The TK-dependent pathway, particularly the PI3-kinase-dependent pathway, seems to
      be critical to the countervailing effect of rHuEPO on IL-1beta and SNP-induced
      VSMC apoptosis.

PMID- 10886573
TI  - Predicting patient outcome from acute renal failure comparing three general
      severity of illness scoring systems.
AB  - BACKGROUND: A major problem of studies on acute renal failure (ARF) arises from a
      lack of prognostic tools able to express the medical complexity of the syndrome
      adequately and to predict patient outcome accurately. Our study was thus aimed at
      evaluating the predictive ability of three general prognostic models [version II
      of the Acute Physiology and Chronic Health Evaluation (APACHE II), version II of
      the Simplified Acute Physiology Score (SAPS II), and version II of the Mortality
      Probability Model at 24 hours (MPM24 II)] in a prospective, single-center cohort
      of patients with ARF in an intermediate nephrology care unit. METHODS: Four
      hundred twenty-five patients consecutively admitted for ARF to the Nephrology and
      Internal Medicine Department over a five-year period were studied (272 males and
      153 females, median age 71 years, interquartile range 61 to 78, median APACHE II
      score 23, interquartile range 18 to 28). Acute tubular necrosis (ATN) accounted
      for 68.7% (292 out of 425) of patients. Renal replacement therapies (hemodialysis
      or continuous hemofiltration) were used in 64% (272 out of 425) of ARF patients.
      RESULTS: Observed mortality was 39.1% (166 out of 425). The mean predicted
      mortality was 36.2% with APACHE II (P = 0.571 vs. observed mortality), 39.3% with
      SAPS II (P = 0.232), and 45.1% with MPM24 II (P < 0.0001). Lemeshow-Hosmer
      goodness-of-fit C and H statistics were 15.67 (P = 0.047) and 12.05 (P = 0.15)
      with APACHE II, 32.53 (P = 0.0001), 39.8 (P = 0.0001) with SAPS II, 21.86 (P =
      0.005), and 20. 24 (P = 0.009) with MPM24 II, respectively. Areas under the
      receiver operating characteristic (ROC) curve were 0.75, 0.77, and 0.85,
      respectively. CONCLUSIONS: The APACHE II model was a slightly better calibrated
      predictor of group outcome in ARF patients, as compared with the SAPS II and
      MPM24 II outcome prediction models. The MPM24 II model showed the best
      discrimination capacity, in comparison with both APACHE II and SAPS II models,
      but it constantly and significantly overestimated mean predicted mortality in ARF
      patients. None of the models provided sufficient confidence for the prediction of
      outcome in individual patients. A high degree of caution must be exerted in the
      application of existing general prognostic models for outcome prediction in ARF
      patients.

PMID- 10886574
TI  - Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk
      in communities study.
AB  - BACKGROUND: Animal and in vitro data suggest that dyslipidemia plays an important
      role in the initiation and progression of chronic renal disease, but few
      prospective studies have been conducted in humans. METHODS: We studied the
      relationship of plasma lipids to a rise in serum creatinine of 0.4 mg/dL or
      greater in 12,728 Atherosclerosis Risk in Communities (ARIC) participants with
      baseline serum creatinine that was less than 2.0 mg/dL in men and less than 1.8
      mg/dL in women. RESULTS: During a mean follow-up of 2.9 years, 191 persons had a
      rise in creatinine of 0.4 mg/dL or greater, yielding an incidence rate of 5.1 per
      1000 person years. Individuals with higher triglycerides and lower high-density
      lipoprotein (HDL) and HDL-2 cholesterol at baseline were at increased risk for a
      rise in creatinine after adjustment for race, gender, baseline age, diabetes,
      serum creatinine, systolic blood pressure, and antihypertensive medication use
      (all P trends </=0.02). The adjusted relative risk for the highest versus lowest
      quartile of triglycerides was 1.65 (95% CI, 1.1, 2.5, P = 0.01) and for HDL was
      0.47 (95% CI, 0.3, 0.8, P = 0.003). These associations were significant in
      participants with normal creatinine (defined as <1.4 mg/dL for men and <1.2 mg/dL
      for women), with diabetes, and without diabetes. The effect of high triglycerides
      was independent of plasma glucose, but was weaker and less consistent after
      further adjustment for fasting insulin in nondiabetics. CONCLUSIONS: High
      triglycerides and low HDL cholesterol, but not low-density lipoprotein
      cholesterol, predict an increased risk of renal dysfunction. The treatment of
      these lipid abnormalities may decrease the incidence of early renal disease.

PMID- 10886575
TI  - Higher incidence of diabetic nephropathy in type 2 than in type 1 diabetes in
      early-onset diabetes in Japan.
AB  - BACKGROUND: Whether the type of diabetes, race, and year and age of diagnosis
      affect the incidence of diabetic vascular complications is unknown. That both
      type 1 and type 2 diabetes occur in the young Japanese population prompted us to
      investigate whether the type of diabetes and the year of diagnosis are related to
      the incidence of nephropathy. METHODS: Of the 17,256 diabetic patients who
      visited the outpatient clinic at our diabetes center between 1965 and 1990, 1578
      (9.1%) had early-onset diabetes (diagnosed before the age of 30); of these, 620
      (39%) had type 1, and 958 (61%) had type 2 diabetes. The incidence of nephropathy
      was analyzed in the patients according to postpubertal duration and year of
      diagnosis. RESULTS: The cumulative incidence of nephropathy after 30 years of
      postpubertal diabetes was significantly higher (P < 0.0001) in type 2 diabetic
      patients (44.4%, 95% CI, 37.0 to 51.8%) than in type 1 diabetic patients (20.2%,
      95% CI, 14.9 to 25.8%). The incidence of nephropathy among type 1 diabetic
      patients has declined during the past two decades, whereas it has not among type
      2 diabetic patients. The rate ratio for type 2 diabetic patients diagnosed
      between 1980 and 1984 relative to type 1 diabetic patients diagnosed in the same
      period was 2.74 (95% CI, 1. 17 to 6.41). CONCLUSIONS: The incidence of
      nephropathy has declined in Japanese patients with type 1 but not in those with
      type 2 diabetes. In young Japanese patients, because of the higher incidence of
      nephropathy in type 2 diabetes and the higher prevalence of type 2 than type 1
      diabetes, type 2 diabetes is likely the major cause of diabetic nephropathy.

PMID- 10886576
TI  - Fetal serum beta2-microglobulin predicts postnatal renal function in bilateral
      uropathies.
AB  - BACKGROUND: Predicting postnatal renal function is crucial for the prenatal
      evaluation of fetal bilateral uropathies. Prenatal ultrasound can identify
      intrauterine terminal renal failure, but is not sensitive enough to identify
      those infants who would survive with an impaired renal function. Because it
      reflects fetal glomerular filtration, fetal serum beta2-microglobulin is a
      potential predictor of postnatal renal function. METHODS: Fetal serum beta2
      microglobulin (beta2m) was assayed in 61 cases of bilateral or low obstructive
      uropathy, 74 controls, and 17 cases of bilateral renal agenesis, and was
      correlated with renal function. RESULTS: Fetal serum beta2m was 3.2 mg/L (range
      1.5 to 4.7) in controls (N = 74), 9.5 mg/L (range 6.7 to 11.3) in bilateral renal
      agenesis (N = 17), 7 mg/L (5.1 to 10.6) in uropathy in which terminal renal
      failure resulted in termination of pregnancy (N = 26), and 3.7 mg/L (range 2.3 to
      11.2) in live births with uropathy (N = 35). In the latter subgroup, fetal serum
      beta2m was significantly and positively correlated (r2 = 0.91) with postnatal
      serum creatinine. All survivors with a postnatal serum creatinine < or =50
      micromol/L ha a fetal serum beta2m lower than 5 mg/L. Four of 6 survivors with a
      postnatal serum creatinine> 50 micromol/L had a fetal serum beta2m greater than 5
      mg/L. CONCLUSION: Fetal serum beta2-microglobulin is a marker for renal function
      and predicts postnatal serum creatinine in bilateral or low fetal obstructive
      uropathy.

PMID- 10886577
TI  - A multicenter trial of mizoribine compared with placebo in children with
      frequently relapsing nephrotic syndrome.
AB  - BACKGROUND: The use of corticosteroids or cytotoxic/immunosuppressive agents such
      as cyclophosphamide, chlorambucil, and cyclosporine for the treatment of
      frequently relapsing nephrotic syndrome (FRNS) is limited because of their
      adverse effects. This study was conducted to evaluate the efficacy and safety of
      mizoribine, a relatively new immunosuppressive drug developed in Japan, in
      children with FRNS. METHODS: A double-blind, placebo-controlled, multicenter
      trial was carried out in children, from 2 to 19 years old, with FRNS. At relapse,
      patients were treated with prednisolone. According to a dynamic allocation,
      mizoribine or a placebo was concurrently administered to each patient.
      Prednisolone was gradually tapered and discontinued within 12 weeks. The test
      drug was maintained for 48 weeks. The primary end point was the relapse rate (the
      total number of relapses/the total treatment days for all patients). Analyses
      were performed according to the intention-to-treat principle. RESULTS: The
      primary analysis was conducted on 99 mizoribine- and 98 placebo-treated patients.
      The relapse rate was lower in the mizoribine group than in the placebo group
      (0.0055 vs. 0.0067; ratio 0.81, 95% CI, 0.61 to 1.05, P = 0.12). The hazard ratio
      of the cumulative remission rate between the two groups was 0.79 (95% CI, 0. 57
      to 1.08). In the subgroups consisting of patients 10 years old or younger, the
      relapse rate ratio between the mizoribine subgroup (54 patients) and the placebo
      subgroup (57 patients) was 0.66 (95% CI, 0. 44 to 0.94, P = 0.017). The hazard
      ratio of the cumulative remission rate between the two subgroups was 0.56 (95%
      CI, 0.37 to 0.85, P = 0. 007). Hyperuricemia was the most common adverse event
      with mizoribine (16%), but was transient. CONCLUSIONS: Compared with the placebo,
      mizoribine significantly decreased the relapse rate and prolonged the remission
      period in the subgroup consisting of patients 10 years old or younger. This drug
      may be useful in young children with FRNS who generally relapse more frequently
      than older children.

PMID- 10886578
TI  - Interaction of cyclosporine and FK506 with diuretics in transplant patients.
AB  - BACKGROUND: The calcineurin inhibitors cyclosporine and FK506 are widely used for
      immunosuppression in solid organ transplantation. One of the side effects of
      these agents is renal magnesium wasting. The site of action and molecular
      mechanism of this effect are not known. We hypothesized that agents such as
      diuretics that cause renal magnesium wasting through a similar action would not
      have an additive effect on magnesium deficiency with calcineurin inhibitors.
      METHODS: The records of 50 heart transplant patients on calcineurin inhibitors
      were reviewed to determine levels of serum magnesium and required replacement
      dose of magnesium, diuretic usage, and other laboratory values. RESULTS: Loop
      diuretics did not change either the magnesium level or magnesium replacement
      requirements in patients on calcineurin inhibitors. In contrast, the thiazide
      diuretic resulted in an increase in serum magnesium and a decrease in magnesium
      replacement. Results were similar when the cyclosporine or FK506 groups were
      evaluated alone. Patients taking FK506 had lower serum magnesium values and
      higher requirements for magnesium replacement compared with patients taking
      cyclosporine. CONCLUSION: We conclude that calcineurin inhibitors and loop
      diuretics have a similar site of action.

PMID- 10886579
TI  - Role of persistent amenorrhea in bone mineral metabolism of young hemodialyzed
      women.
AB  - BACKGROUND: Chronic renal failure in women is frequently associated with
      endocrine disturbances leading to menstrual disorders. However, most studies on
      renal osteodystrophy have not taken into account the possible role of these
      hormonal disturbances on the pathogenesis of bone alterations seen in these
      patients. In the present study, we evaluated bone mineral metabolism in a group
      of young hemodialyzed women with persistent amenorrhea and compared them with
      similar women with regular menstruation. METHODS: We studied 74 women who were
      further subdivided into 43 women with regular menstrual periods and 31 women with
      persistent amenorrhea, defined as the absence of menstrual bleeding for more than
      six months. In all patients, we performed a bone mineral density (BMD) analysis
      and simultaneously evaluated different biochemical parameters, intact parathyroid
      hormone (iPTH), sexual hormone determinations that included total estradiol,
      follicle-stimulating (FSH), and luteinizing hormone and markers of bone
      resorption such as the procollagen type 1 cross-linked carboxy-terminal
      telopeptide (ICTP). RESULTS: Serum calcium, phosphorus, and iPTH were similar in
      both groups. Serum alkaline phosphatase was higher in amenorrheic women. Although
      the total serum estradiol concentration was normal in the amenorrheic women when
      compared with nonuremic women, the values were significantly lower than those in
      regularly menstruating women. Serum FSH and ICTP values were significantly higher
      in the amenorrheic women. Trabecular BMD in the lumbar spine was also
      significantly lower in the amenorrheic women compared with regularly menstruating
      dialysis patients. Lumbar spine BMD and total estradiol levels correlated
      significantly in the amenorrheic group. CONCLUSIONS: These studies show that
      persistent amenorrheic young women on dialysis have lower trabecular BMD and
      evidence of increased bone resorption when compared with normal menstruating
      women on dialysis. The possible impact of these results in the natural history of
      the uremic osteodystrophy remains to be determined.

PMID- 10886580
TI  - Calculated nitrogen balance in hemodialysis patients: influence of protein
      intake.
AB  - BACKGROUND: Optimal nutrient intake is important in the maintenance of a positive
      nitrogen balance in hemodialysis (HD) patients. The objectives of this study were
      (1) to assess the influence of two levels of protein intakes on nitrogen balance
      in stable adult HD patients, and (2) to identify a minimum level of protein
      intake that would result in a negative nitrogen balance, so that preliminary
      recommendations may be made in Indian patients on maintenance HD (MHD). METHODS:
      Stable, adult, nondiabetic MHD patients were recruited after informed consent
      into a cross over trial with a high-protein (HP) diet [1.2 g/kg ideal body weight
      (IBW)/day), followed by a low-protein (LP) diet (0.6 g/kg IBW/day] after
      appropriate periods of equilibration; for both diets, 50% of protein was of high
      biological value, and calorie intake was 35 kCal/kg IBW/day. Duplicate meals and
      residues were weighed, homogenized, and stored at -20 degrees C for analysis of
      dietary N by the Kjeldahl method, used to check the consistency of the N content
      of the diet supplied. Pre- and post- (30-minute equilibrated) blood urea samples
      were drawn, and details of weights and other HD parameters were recorded.
      Interdialytic urine collections for urea were obtained. N input came from dietary
      protein calculated as 16% of the weight of biological protein; N output was
      calculated using blood-side urea measurements and urinary urea excretion and was
      the sum of urea N (UN) and nonurea N (NUN) losses (assumed to be equal to 0.031 g
      N/kg/day). RESULTS: Fifteen patients were recruited. Twelve patients completed
      both limbs of the study. The mean age was 30.3 +/- 12.7 years. The body mass
      index was 18.9 +/- 2.4. Serum albumin was 3.8 +/- 0.35 g/dL, and Kt/V
      (equilibrated) was 1.17 +/- 0.3 g/dL. Protein consumed was 1.06 +/- 0.18 g/kg
      IBW/day in the HP limb versus 0.61 +/- 0.1 g/kg IBW/day in the LP limb (P =
      0.000). Energy intake was 33 +/- 6.5 vs. 32.8 +/- 6. 7 kCal/kg IBW/day,
      respectively (P = 0.8). The normalized protein N appearance (nPNA) was 0.88 +/-
      0.2 g/kg/day in the HP limb versus 0. 78 +/- 0.2 g/kg/day in the LP limb (P =
      0.02). Dietary N was 73.5 +/- 15.3 g in the HP week and 42.5 +/- 7.5 g in the LP
      week (P = 0. 000). The difference between this and the sum of (UN + NUN) losses
      over the week was 29 +/- 13.2 g versus 1.2 +/- 8.1 g, respectively (P = 0.001),
      showing a strong, uniformly positive nitrogen balance with HP diet and neutral to
      negative nitrogen balance with LP diet. The ratio of dietary protein intake (DPI)
      to nPNA was significantly lower (anabolic) in the HP limb (0.7 +/- 0.2 vs. 1.12
      +/- 0.3, P = 0. 000). On a scatter plot of nPNA to DPI, a catabolic relationship
      was demonstrated below a DPI of 0.75 g/kg/day (95% CI, 0.65 to 0.85 g/kg/day).
      CONCLUSION: A DPI of approximately 1.1 g/kg/day produces a positive nitrogen
      balance and 0.6 g/kg/day a neutral to negative nitrogen balance, demonstrating
      protein anabolism as a function of protein intake. It is suggested that a protein
      intake of 0.85 g/kg/day should be considered unsafe. These conclusions apply in
      stable nondiabetic adult HD patients in the setting of adequate dialysis and
      adequate calorie intake.

PMID- 10886581
TI  - The acute-phase response varies with time and predicts serum albumin levels in
      hemodialysis patients. The HEMO Study Group.
AB  - BACKGROUND: Cross sectional studies have established that the serum albumin level
      is dependent on serum levels of acute-phase proteins (APPs) or cytokine levels in
      hemodialysis patients. While the acute-phase response is generally associated
      with acute inflammatory events, a cross sectional analysis relating laboratory
      values to outcomes assumes these values to be unchanging. The longitudinal
      relationship among laboratory measurements and how they vary over time in a
      population of patients are unknown. METHODS: Patients who were enrolled in the
      HEMO Study were recruited into an ancillary longitudinal study to establish the
      predictive effect of temporal variation in the levels of APPs and of temporal
      variation in normalized protein catabolic rate (nPCR) on the serum albumin
      concentration. nPCR was measured monthly using a double-pool method. The positive
      APPs-C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1-AG), and
      ceruloplasmin-and the negative APP-transferrin (Trf)-were measured in serum
      obtained before each dialysis session for six weeks and then monthly in 37
      hemodialysis patients. A random coefficient regression analysis was used to
      assess the association of serum albumin with other measured parameters at each
      time point, as well as fixed patient characteristics. RESULTS: The within-subject
      coefficients of variation of albumin (median, range of 25th to 75th percentiles;
      median, 0.0614; range, 0.0485 to 0.0690) were significantly less than that of
      APPs (CRP, median, 0.878; range, 0.595 to 1.314, P < 0. 05; and alpha1 AG,
      median, 0.173; range, 0.116 to 0.247, P < 0.05). The levels of APPs and albumin
      varied considerably over time. The primary predictor of current albumin was the
      current CRP level (P = 0.0014). nPCR also was a significant predictor for albumin
      levels (P = 0.0440) after controlling for the effect of APPs, suggesting an
      effect of nPCR on serum albumin concentration irrespective of the acute-phase
      response. Age and the presence of an arteriovenous graft were significant
      predictors that were associated with reduced albumin. CONCLUSIONS: The acute
      phase response is intermittent and is not a continuous feature in individual
      dialysis patients. Levels of APPs are the most powerful predictors for the levels
      of albumin concentration in hemodialysis in a longitudinal setting. Since
      variations in albumin are small, measurement of variations in APPs may provide
      greater insight into the dynamics of clinically relevant processes.

PMID- 10886582
TI  - Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients.
AB  - BACKGROUND: Cardiovascular diseases are the most common causes of death among
      chronic hemodialysis patients, yet the risk factors for these events have not
      been well established. METHODS: In this cross-sectional study, we examined the
      relationship between several traditional cardiovascular disease risk factors and
      the presence or history of cardiovascular events in 936 hemodialysis patients
      enrolled in the baseline phase of the Hemodialysis Study sponsored by the U.S.
      National Institutes of Health. The adjusted odds ratios for each of the selected
      risk factors were estimated using a multivariable logistic regression model,
      controlling for the remaining risk factors, clinical center, and years on
      dialysis. RESULTS: Forty percent of the patients had coronary heart disease.
      Nineteen percent had cerebrovascular disease, and 23% had peripheral vascular
      disease. As expected, diabetes and smoking were strongly associated with
      cardiovascular diseases. Increasing age was also an important contributor,
      especially in the group less than 55 years and in nondiabetic patients. Black
      race was associated with a lower risk of cardiovascular diseases than non-blacks.
      Interestingly, neither serum total cholesterol nor predialysis systolic blood
      pressure was associated with coronary heart disease, cerebrovascular disease, or
      peripheral vascular disease. Further estimation of the coronary risks in our
      cohort using the Framingham coronary point score suggests that traditional risk
      factors are inadequate predictors of coronary heart disease in hemodialysis
      patients. CONCLUSIONS: Some of the traditional coronary risk factors in the
      general population appear to be also applicable to the hemodialysis population,
      while other factors did not correlate with atherosclerotic cardiovascular
      diseases in this cross-sectional study. Nontraditional risk factors, including
      the uremic milieu and perhaps the hemodialysis procedure itself, are likely to be
      contributory. Further studies are necessary to define the cardiovascular risk
      factors in order to devise preventive and interventional strategies for the
      chronic hemodialysis population.

PMID- 10886583
TI  - Need for an incentive-based reimbursement policy toward quality care for dialysis
      patient management.
AB  - BACKGROUND: In view of the growing dialysis population and the increasing
      reimbursement cost in the industrialized countries, a critical evaluation of the
      dialysis economy is warranted. METHODS: Data for the reimbursement and dialysis
      patients' statistics were collected from the National Medical Care Expenditure
      (NMCE), 1979-1996, which was published by the Japanese government, and the
      article "An overview of regular dialysis treatment in Japan," 1979-1998, by the
      Japanese Society for Dialysis Therapy, as well as unpublished data from the
      Yokohama Dai-ichi Hospital and 10 affiliated urban dialysis centers. RESULTS:
      From 1979 to 1996, the dialysis population increased 5.2 times and the NMCE
      increased 2.5 times, whereas the end-stage renal disease (ESRD) payment increased
      only 1.8 times. Because of a drastic reduction in the dialyzer cost and the
      dialysis-related technical fee, both the percentage of ESRD-related payment
      within NMCE and ESRD payment per capita per year decreased from 5.4 to 4.1% and
      from 16.3 million yen to 5.6 million yen, respectively. Despite this drastic cost
      reduction, the patient survival and quality of life determined by the social
      rehabilitation rate did not decline. CONCLUSION: The Japanese health insurance
      policy for dialysis management achieved a successful cost cut during the 1979
      1996 period by using an incentive-based payment system toward quality care.
      However, the forthcoming further exponential increase in the dialysis population
      may put the dialysis economy and hence dialysis care quality in jeopardy. Effort
      must be made to reduce the ESRD-related cost through prevention of the
      progression of kidney diseases, propagation of renal transplantation, and
      internationalization of continuous ambulatory peritoneal dialysis and
      erythropoietin cost. A reduction in dialysis reimbursement, if necessary, must be
      achieved through an incentive-based system toward quality patient care.

PMID- 10886584
TI  - N-terminal fragments of the proatrial natriuretic peptide in patients before and
      after hemodialysis treatment.
AB  - BACKGROUND: Fragments derived from the prohormone of alpha-human atrial
      natriuretic peptide (alpha-ANP) in patients with cardiac failure are more closely
      related to the disease state than intact alpha-ANP. METHODS: Specific
      immunoassays have been developed to detect proANP 1-30, proANP 31-67, and proANP
      1-98. Plasma concentrations of these fragments were determined in 122
      hemodialysis patients with and without cardiac dysfunction, with and without
      hypertension, as well as with and without dialysis-associated hypotensive
      episodes either before or after a regularly scheduled hemodialysis session. The
      effects of different dialyzer membranes were also evaluated. The results of these
      assays along with other markers of volume regulation such as alpha-ANP and cyclic
      3',5' guanosine monophosphate (cGMP) were compared with those of healthy
      controls. RESULTS: Predialytic and postdialytic plasma concentrations of the
      proANP fragments were markedly higher in uremic patients than in controls (98
      fold for proANP 1-98, 56-fold for proANP 31-67, and 35-fold for proANP 1-30). All
      proANP fragments, alpha-ANP, and cGMP decreased during hemodialysis. A strong
      linear correlation was found between predialytic and postdialytic plasma levels.
      There was no correlation, however, with the amount of fluid removed during
      hemodialysis. Patients with altered left ventricular hemodynamics displayed
      significantly higher plasma concentrations of all proANP fragments and alpha-ANP,
      but not cGMP, than patients with normal cardiac function. Hemodialysis patients
      with moderate or severe hypertension had higher concentrations of proANP
      fragments, alpha-ANP, and cGMP than patients with normal blood pressure or
      patients with only mild hypertension. There was no significant difference in
      circulating levels of proANP peptides, alpha-ANP, and cGMP between patients with
      and without frequent dialysis-associated hypotensive episodes. Cellulose
      triacetate dialyzers reduced plasma levels of proANP 1-30, proANP 31-67, and
      proANP 1-98 significantly more than polysulfone dialyzers, but alpha-ANP and cGMP
      levels were not different. CONCLUSIONS: Circulating alpha-ANP and proANP
      fragments are influenced by a variety of factors such as end-stage renal disease,
      hemodialysis treatment, dialyzer membrane material, cardiac dysfunction, and
      hypertension. Therefore, these are not useful markers to accurately estimate
      volume status in hemodialysis patients.

PMID- 10886585
TI  - Fungal peritonitis in children receiving peritoneal dialysis: a report of the
      NAPRTCS.
AB  - BACKGROUND: The rarity of fungal peritonitis (FP) in children receiving chronic
      peritoneal dialysis (PD) has limited the amount of information available
      regarding the risk factors and management associated with this infection.
      METHODS: We reviewed all cases of FP occurring in patients entered into the
      dialysis registry of the NAPRTCS between January 1992 and May 1996 in an attempt
      to identify risk factors for infection, treatment strategies, and patient outcome
      data. A total of 1592 patients who were less than 21 years of age were enrolled
      in the dialysis registry and received maintenance PD during the period of
      observation. RESULTS: Of the total 1729 episodes of peritonitis in these patients
      occurring over 1732 patient-years of follow-up, FP accounted for 51 (2.9%) of the
      episodes. The patients on PD who developed FP were similar to those who did not
      develop FP with regard to race, gender, dialysis modality, and dialysis access
      characteristics. The overall peritonitis rate in patients who developed FP was
      2.2 episodes per patient-year compared with 0.96 episodes per patient-year in the
      patients who did not develop this infection (P < 0.0001). In 25 (49%) cases, the
      FP was the patient's initial episode of peritonitis. Whereas recent antibiotic
      usage was present in 23 (56%) of 41 patients with FP, there was no statistically
      significant relationship (P = 0.26) noted between the presence of a gastrostomy
      and the development of FP. Candida species caused 33 of 42 (78.6%) FP episodes.
      Therapy consisted of PD catheter removal and Amphotericin B in the majority of
      patients. Six months after diagnosis, 27 patients remained on PD, twelve patients
      were receiving hemodialysis, and only three patients had died, in each case for
      reasons unrelated to their FP episode. CONCLUSION: FP is an infrequent cause of
      peritonitis in children receiving chronic PD. The presence of a gastrostomy does
      not appear to predispose patients to the development of this infection, and
      successful therapy most often consists of a combination of antifungal medication
      and dialysis catheter removal. The outcome of FP in children appears to be more
      favorable than in the adult dialysis population.

PMID- 10886586
TI  - A prospective randomized trial of three different sizes of core-cutting needle
      for renal transplant biopsy.
AB  - BACKGROUND: Needle-core biopsy remains one of the most important investigations
      in cases of renal allograft dysfunction. The size and quality of the biopsy
      material are likely to be important factors in achieving an accurate diagnosis.
      The aim of this study was to compare the success and complication rates of renal
      transplant biopsy procedures using three differently sized needles. METHODS: One
      hundred renal allograft recipients undergoing transplant biopsy using an
      automated needle core method were randomized to a 14, 16, or 18 gauge (G) needle.
      The size of each biopsy core was measured, and the presence or absence of renal
      cortical and medullary tissue and the number of glomeruli were recorded.
      Assessments of the ease with which the procedure was performed, the diagnostic
      usefulness of the biopsy material, and the discomfort associated with the
      procedure were made using verbal response and linear analog scales. RESULTS:
      Fourteen G biopsy cores (N = 33) were larger than both 16G (N = 33) and 18G (N =
      34) cores and contained more gomeruli (mean number for 14G, 16G, and 18G = 15, 11
      and 9, respectively). There were no differences in the ease of use of the three
      needle types, but scores for diagnostic usefulness were higher for 14G versus 18G
      and 16G versus 18G. The 14G needle was associated with significantly more pain
      than the two smaller needles when this was assessed using a linear analog score.
      Macroscopic hematuria occurred in eight patients, but there were no differences
      in complications rates between the three groups. CONCLUSIONS: All three needle
      sizes are safe for use in renal allograft biopsy using a semiautomated biopsy
      gun. The larger needles provide more tissue and glomeruli and, thus, are more
      diagnostically useful. Use of a 14G needle may be associated with more pain, and
      the 16G needle appears to offer the best compromise between diagnostic usefulness
      and patient acceptability.

PMID- 10886587
TI  - Increased risk of hip fracture among patients with end-stage renal disease.
AB  - BACKGROUND: Although patients with end-stage renal disease (ESRD) are at
      increased risk for bone loss, the risk of hip fracture in this population is not
      known. We compared the risk of hip fracture among dialysis patients with the
      general population. METHODS: We used data from the United States Renal Data
      System (USRDS) to identify all new Caucasian dialysis patients who began dialysis
      between January 1, 1989, and December 31, 1996. All hip fractures occurring
      during this time period were ascertained. The observed number of hip fractures
      was compared with the expected number based on the experience of residents of
      Olmstead County (MN, USA). Standardized incidence ratios were calculated as the
      ratio between observed and expected. The risk attributable to ESRD was calculated
      as the difference between the observed and expected rate of hip fracture per 1000
      person-years. RESULTS: The number of dialysis patients was 326,464 (55.9% male
      and 44.1% female). There were 6542 hip fractures observed during the follow-up
      period of 643, 831 patient years. The overall incidence of hip fracture was 7.45
      per 1000 person years for males and 13.63 per 1000 person years for females. The
      overall relative risk for hip fracture was 4.44 (95% CI, 4.16 to 4.75) for male
      dialysis patients and 4.40 (95% CI, 4.17 to 4.64) for female dialysis patients
      compared with people of the same sex in the general population. While the age
      specific relative risk of hip fracture was highest in the youngest age groups,
      the added risks of fracture associated with dialysis rose steadily with
      increasing age. The relative risk of hip fracture increased as time since first
      dialysis increased. CONCLUSIONS: The overall risk of hip fracture among Caucasian
      patients with ESRD is considerably higher than in the general population,
      independent of age and gender.

PMID- 10886588
TI  - Importance of dialysis adequacy in mortality and morbidity of chinese CAPD
      patients.
AB  - BACKGROUND: In continuous ambulatory peritoneal dialysis (CAPD), the impact of
      dialysis adequacy on patient outcome is well established in Caucasian patients
      but is less clear in Asian patients. Recent evidence suggests that Asian dialysis
      patients enjoy better overall survival. We hypothesize that dialysis adequacy may
      be less important in determining outcome for this ethnic group. METHODS: We
      performed a single-center prospective observational study. From September 1995,
      we enrolled 150 existing and 120 new CAPD patients. They were followed for up to
      three years. We monitored dialysis adequacy and nutritional indices, including
      Kt/V, weekly creatinine clearance (CCr), residual glomerular filtration rate
      (GFR), normalized protein catabolic rate (NPCR), percentage of lean body mass
      (%LBM), and plasma albumin level. Clinical outcomes included mortality, technique
      failure, and duration of hospitalization. RESULTS: The duration of study follow
      up was 22.1 +/- 12.3 months. In our study population, 136 were male. Seventy were
      diabetic (25.9%), and 212 were treated with 6 L exchanges per day (78.5%). The
      body weight was 59.3 +/- 9.4 kg. Baseline total Kt/V was 1.78 +/- 0.41,
      peritoneal Kt/V 1.48 +/- 0.36, and median residual GFR 0.98 mL/min (range 0 to
      7.45). Two-year patient survival was 83.0%, and technique survival was 72.8%.
      Multivariate analysis showed that the duration of dialysis, diabetes, %LBM, index
      of dialysis adequacy (Kt/V or CCr), residual GFR, and requirement of a helper for
      CAPD exchanges were independent factors of patient survival; serum albumin,
      adequacy index (Kt/V or CCr), and requirement of a helper were independent
      factors of technique survival. Duration of dialysis, body weight, requirement of
      helper, cardiovascular disease, HBsAg carrier, serum albumin, and CCr had
      independent effects on hospitalization. The peritoneal component of Kt/V or CCr
      had no independent effect on any outcome parameter. When the prevalent and new
      CAPD cases were analyzed separately, Kt/V predicted survival only for new CAPD
      cases. CONCLUSIONS: Our results show that dialysis adequacy has significant
      impact on outcome of Asian CAPD patients. Although we have excellent medium-term
      patient and technique survival, this favorable outcome should not prevent health
      care workers from providing adequate dialysis to Asian patients. The reason of
      discrepancy in outcome between Asian and Caucasian dialysis patients requires
      further study.

PMID- 10886589
TI  - Comparing different methods of assessing body composition in end-stage renal
      failure.
AB  - BACKGROUND: Accurate measurement of nutritional status in patients with end-stage
      renal disease is important because of its clear association with prognosis. Total
      body water (TBW) has additionally been recently recognized as an independent
      prognostic value because of its relationship with hypertension and cardiac
      morbidity. The current study was designed to assess the utility of surrogate
      markers of nutritional state and TBW in patients with end-stage renal disease.
      METHODS: Fifty-four patients with renal disease were studied. TBW obtained using
      the deuterium dilution technique was compared with estimates derived from
      anthropometric measures of TBW, including 58% body weight, Watson equations, and
      bioelectrical impedance analysis (BIA). Anthropometrically derived fat-free mass
      (FFM) was compared with BIA-derived estimates. Total body nitrogen (TBN)
      measurements were correlated with TBW estimates and BIA-derived resistance.
      RESULTS: TBW was significantly underestimated by the Watson equation (mean
      difference, -1.751 L, P = 0.01) and the 58% body weight approximation
      significantly overestimated it (mean difference, 1.792 L, P = 0.04). The Kushner
      BIA estimation of TBW did not significantly differ from that of the gold standard
      determined from D2O dilution (mean difference, -1.221 L, P = 0.12) and was also
      the method that showed the best agreement with the D2O estimate. However, the
      limits of agreement were large. Accurate prediction equations for FFM (FFM = 
      21.768 + 0.001 x ht2 + 6630.669 x 1/R + 0.312 x wt, R2 = 0.95) and TBN (TBN = 
      668.324 - 3.963 x age + 10.133 x wt + 0. 045 x ht2 + 32141.457 x 1/R, R2 = 0.91)
      were derived from BIA obtained resistance. CONCLUSIONS: The estimation of TBW
      varies significantly depending on the method of calculation. BIA is the most
      accurate surrogate marker for the measurement of both TBW and other parameters of
      body composition.

PMID- 10886590
TI  - Role of different dialysis membranes in the release of interleukin-6-soluble
      receptor in uremic patients.
AB  - BACKGROUND: Interleukin-6 (IL-6) exerts its actions through a cell-surface
      receptor system that consists of two transmembrane subunits: the IL-6 binding
      glycoprotein gp 80 (IL-6R) and the signal-transducing component (gp 130). Soluble
      forms of the IL-6R (sIL-6R) are generated by shedding of the membrane-associated
      proteins. The sIL-6R binds the ligand IL-6 with comparable affinity as the
      membrane-associated IL-6R and enhances the actions of IL-6. METHODS: Our aim was
      to evaluate the role of both uremia and different dialysis membranes on
      peripheral blood mononuclear cell (PBMC) release (either in absence or in
      presence of mitogen stimulation) and plasma levels of sIL-6R. Ten patients
      chronically dialyzed with cuprophan membranes (CU), eight patients on regular
      dialysis treatment with polymethylmethacrylate (PMMA) membranes, 11 uremic
      nondialyzed patients (UR), and 12 healthy subjects (CON) were included in the
      study. RESULTS: PBMCs harvested from CU spontaneously released significantly (P <
      0.01) greater amounts of sIL-6R (881.8 +/- 80.1 pg/mL), as compared with CON
      (267.5 +/- 26.5 pg/mL), UR (258.4 +/- 38.1 pg/mL), and PMMA (288.4 +/- 24.6
      pg/mL). Under mitogenic stimulation, the sIL-6R release was significantly (P <
      0.01) increased in all groups. The greater PBMC production of sIL-6R in CU was
      followed by significantly (P < 0.01) higher levels of circulating soluble
      receptors (48.7 +/- 2.5 ng/mL, 60%), as compared with CON (30.5 +/- 1.9 ng/mL).
      UR also showed high circulating levels of sIL-6R (53.3 +/- 5.9 ng/mL), probably
      secondary to an impaired urinary excretion. Circulating levels of sIL-6R in PMMA
      were comparable to CON (30.3 +/- 3.3 ng/mL). Either the absence of monocyte
      activation or the adsorption of sIL-6R on the hydrophobic PMMA surface could
      explain this finding. CONCLUSIONS: These results suggest an important role for
      poor dialysis biocompatibility of CU on the release of sIL-6R, which increases
      sIL-6R plasma levels, thereby enhancing the inflammatory effects of IL-6.

PMID- 10886591
TI  - Advanced glycation and lipidoxidation of the peritoneal membrane: respective
      roles of serum and peritoneal fluid reactive carbonyl compounds.
AB  - BACKGROUND: Advanced glycation of proteins has been incriminated in the
      progressive alteration of the peritoneal membrane during chronic peritoneal
      dialysis (PD). Advanced glycation end products (AGEs) result from a modification
      of proteins by reactive carbonyl compounds (RCOs). RCOs resulting from glucose
      breakdown are present in commercial PD fluid. They also accumulate in uremic
      plasma. The present study was undertaken to evaluate the respective contribution
      of these two sources of RCOs in the genesis of peritoneal AGEs. METHODS: Three
      major RCOs formed during heat sterilization of PD fluid, that is, glyoxal,
      methylglyoxal, and 3-deoxyglucosone, and total RCOs were measured in commercial
      PD fluid and in PD effluent. The generation of pentosidine, used as a surrogate
      marker for AGEs, during one-week incubations of PD fluid and effluent samples
      fortified with bovine serum albumin (BSA) was measured by high-performance liquid
      chromatography. Peritoneal samples were stained with antibodies specific for two
      AGEs derived from carbohydrate-dependent RCOs, Nepsilon-(carboxymethyl)lysine
      (CML) and pentosidine, or for two advanced lipoxidation end products (ALEs)
      derived from lipid-dependent RCOs, malondialdehyde (MDA)-lysine and 4
      hydroxynonenal (HNE)-protein adduct. RESULTS: Glyoxal, methylglyoxal, and 3
      deoxyglucosone were identified in commercial PD fluid. Their levels in PD
      effluents decreased with dwell time probably by diffusion into blood circulation.
      In contrast, the levels of total RCOs were initially low in commercial PD fluid,
      increased in PD effluent with dwell time probably by diffusion from circulation
      into the peritoneal cavity, and after 12 hours, reached values observed in uremic
      serum. The relevance of the rise in total RCOs for AGE formation is demonstrated
      by a parallel increase in the generation of pentosidine during incubations of PD
      effluents. In contrast with RCOs present in glucose-rich PD fluid, RCOs diffusing
      from uremic circulation originate from both carbohydrates and lipids. Their role
      in the modification of peritoneal proteins is demonstrated by the
      immunohistochemical study of peritoneal tissue. Two AGEs and two ALEs increase in
      parallel in the mesothelial layers and in vascular wall of small arteries in the
      peritoneum. CONCLUSIONS: Protein modification of the peritoneum is determined not
      only by RCOs originating in PD fluid, but also by RCOs originating from the
      uremic circulation. The present data might be relevant to current attempts to
      improve PD fluid toxicity by lowering its glucose content.

PMID- 10886592
TI  - A calcimimetic agent lowers plasma parathyroid hormone levels in patients with
      secondary hyperparathyroidism.
AB  - BACKGROUND: The calcimimetic agent R-568 lowers plasma parathyroid hormone (PTH)
      levels in hemodialysis patients with mild secondary hyperparathyroidism, but its
      efficacy in those with more severe secondary hyperparathyroidism has not been
      studied. METHODS: Twenty-one patients undergoing hemodialysis three times per
      week with plasma PTH levels between 300 and 1200 pg/mL were randomly assigned to
      15 days of treatment with either 100 mg of R-568 (N = 16) or placebo (N = 5).
      Plasma PTH and blood ionized calcium levels were measured at intervals of up to
      24 hours after oral doses on days 1, 2, 3, 5, 8, 11, 12, and 15. RESULTS:
      Pretreatment PTH levels were 599 +/- 105 (mean +/- SE) and 600 +/- 90 pg/mL in
      subjects given R-568 or placebo, respectively, and values on the first day of
      treatment did not change in those given placebo. In contrast, PTH levels fell by
      66 +/- 5%, 78 +/- 3%, and 70 +/- 3% at one, two, and four hours, respectively,
      after initial doses of R-568, remaining below pretreatment values for 24 hours.
      Blood ionized calcium levels also decreased after the first dose of R-568 but did
      not change in patients given placebo. Despite lower ionized calcium
      concentrations on both the second and third days of treatment, predose PTH levels
      were 422 +/- 70 and 443 +/- 105 pg/mL, respectively, in patients given R-568, and
      values fell each day by more than 50% two hours after drug administration.
      Predose PTH levels declined progressively over the first nine days of treatment
      with R-568 and remained below pretreatment levels for the duration of study.
      Serum total and blood ionized calcium concentrations decreased from pretreatment
      levels in patients given R-568, whereas values were unchanged in those given
      placebo. Blood ionized calcium levels fell below 1.0 mmol/L in 7 of 16 patients
      receiving R-568; five patients withdrew from study after developing symptoms of
      hypocalcemia, whereas three completed treatment after the dose of R-568 was
      reduced. CONCLUSIONS: The calcimimetic R-568 rapidly and markedly lowers plasma
      PTH levels in patients with secondary hyperparathyroidism caused by end-stage
      renal disease.

PMID- 10886593
TI  - Peritoneal dialysis adequacy and risk of death.
AB  - BACKGROUND: The purpose of this study was to evaluate the relationship between
      dialysis dose, patient characteristics, and medical comorbidities on mortality in
      chronic peritoneal dialysis patients. METHODS: This work comprised a study cohort
      of 1446 patients obtained from a random sample of chronic peritoneal dialysis
      patients from each dialysis center in three southeastern states. Data collected
      on a standardized form were used to calculate weekly Kt/V urea and creatinine
      clearance. Data were linked to Network files containing data on patient
      demographic and medical comorbidities. RESULTS: Both weekly Kt/V urea and
      creatinine clearance were measured at least once in only 60.5% of continuous
      ambulatory peritoneal dialysis (CAPD) patients and 63.7% of cycler patients.
      Among the 873 patients who had at least one calculable adequacy measure, the mean
      (+/-SD) weekly Kt/V urea was 2.13 +/- 0.55, and the normalized mean weekly
      creatinine clearance was 62.9 +/- 20.4 L/week/m2. During the seven month period
      of follow-up, there were 140 deaths. In separate logistic regression models that
      included all of the studied risk factors, using separate variables for the
      urinary and peritoneal components of dialysis adequacy, each 10 L/week/1.73 m2
      increase in the urinary component of weekly creatinine clearance was associated
      with a 40% decreased risk of death, and each 0.1 unit increase in the urinary
      component of weekly Kt/V urea was associated with a 12% decreased risk of death.
      In contrast, the dialysate components of neither weekly creatinine clearance nor
      weekly Kt/V urea were predictive of death. Other factors that were associated
      with an increased risk of death included increasing age, diabetes mellitus as the
      cause of end-stage renal disease (ESRD), and a history of myocardial infarction.
      CONCLUSIONS: Residual renal function, as expressed by weekly creatinine clearance
      or Kt/V urea, is an important predictor of death in chronic peritoneal dialysis
      patients. The nonsignificant findings regarding peritoneal clearances and
      mortality may possibly be secondary to the narrow range of peritoneal clearances
      in this study cohort.

PMID- 10886594
TI  - Why we block angiotensin II.

PMID- 10886595
TI  - Is angiotensin II's role in fibrosis as easy as PAI(-1)?

PMID- 10886596
TI  - Hepatitis C virus in hemodialysis patients.

PMID- 10886597
TI  - Reply from the authors

PMID- 10886599
TI  - Reply from the authors

PMID- 10886598
TI  - Diagnosing sickle cell disease.

PMID- 10886601
TI  - Reply from the authors

PMID- 10886600
TI  - Association of mortality and morbidity with bioimpedance analysis.

PMID- 10886603
TI  - Reply from the authors

PMID- 10886602
TI  - Statistical error in pamidronate study?

PMID- 10886604
TI  - Nephrology forum: apoptotic regulatory proteins in renal injury.

PMID- 10886605
TI  - Indigo production by naphthalene-degrading bacteria.
AB  - A wild-type naphthalene-degrading strain Pseudomonas putida RKJ1 and two
      recombinant strains each of Ps. putida and Escherichia coli carrying the genes
      for naphthalene degradation on a recombinant plasmid pRKJ3, produced indigo and
      indirubin pigments from indole. Naphthalene, salicylate and IPTG induced cells of
      naphthalene-degrading recombinant bacteria produced up to two times higher indigo
      compared with the uninduced cells. The maximum rates of indigo formation by Ps.
      putida RKJ1, Ps. putida RKJ5/pRKJ3, Ps. putida KT2442/pRKJ3, E. coli TB1/pRKJ3
      and E. coli AB1157/pRKJ3 were 0.60, 0.80, 0.60, 1.20 and 1.50 nmol min-1 mg dry
      biomass-1, respectively, using indole as the substrate. The apparent Km values of
      indigo formation by these same bacteria were 0.22, 0.15, 0.10, 0. 21 and 0.20
      mmol l-1, respectively, again using indole as the substrate. The present study
      revealed that E. coli AB1157 was the most efficient of the hosts tested for the
      expression of the plasmid encoded genes (pRKJ3) from the wild-type strain Ps.
      putida RKJ1. In addition, both recombinant E. coli strains were capable of
      producing indigo directly from nutrient medium.

PMID- 10886606
TI  - Neuraminidase-producing ability of intestinal bacteria isolated from coastal
      fish.
AB  - The neuraminidase-producing ability of bacteria from coastal fish intestines and
      their environments was determined using a fluorogenic substrate, 2'-(4
      methylumbelliferyl)-alpha-D-N-acetylneuraminic acid. Of 836 isolates examined,
      758 (90.7%) produced little or no neuraminidase (< 0.0002 U ml-1) while 78 (9.3%)
      produced >/= 0.0002 U neuraminidase ml-1. Of note, 10% of vibrios from fish
      intestines could produce neuraminidases, and 9% did it efficiently. This result
      suggests that the vibrios capable of producing neuraminidases are able to
      colonize and establish in the intestinal tract of coastal fish to some extent.
      Additionally, as many as 58% of the Vibrio isolates with high abilities were
      tentatively identified as Vibrio damsela.

PMID- 10886607
TI  - Efficacy of flagellin gene typing for epidemiological studies of Campylobacter
      jejuni in poultry estimated by comparison with macrorestriction profiling.
AB  - Thirty isolates of Campylobacter jejuni isolated from 29 different Danish broiler
      flocks were chosen for the evaluation of PCR-Fla typing as a genotyping tool.
      Except for two isolates that originated from the same broiler flock, the isolates
      were clearly distinguishable on basis of their macrorestriction profiles using
      the restriction endonucleases SmaI and KpnI. PCR-Fla typing of the 30 isolates
      yielded 16 distinct genotypes, whereas one isolate was untypeable by this method.
      The dominant PCR-Fla type (1/1) was shared by eight isolates, and five additional
      Fla groups containing two or three isolates were obtained. The PCR-Fla type of
      one isolate changed spontaneously after five subcultures, illustrating the
      relative plasticity of the gene locus. Comparison of MRPs within and between Fla
      types support the view that some PCR-Fla types may be conserved within clonal
      lines. It is concluded that PCR-Fla typing is useful as a genotyping tool in
      large-scale epidemiological studies but that additional analyses with other
      methods are required to properly define interstrain relationships.

PMID- 10886608
TI  - Susceptibility of multiresistant strains of Burkholderia cepacia to honey.
AB  - Twenty strains of Burkholderia cepacia, isolated principally from the sputum of
      cystic fibrosis patients, were tested for their susceptibility to eight
      antibiotics with a modified Kirby-Bauer Disc diffusion technique. All strains
      exhibited multiple but not identical patterns of antibiotic resistance. The
      sensitivity of all strains to honey was assessed with an agar dilution method.
      All strains exhibited susceptibility to concentrations of honey below 6% (v/v).
      This suggests that honey may have a potential role in the clinical management of
      B. cepacia infections.

PMID- 10886609
TI  - Production of cutinolytic esterase by filamentous bacteria.
AB  - Thirty-eight strains of filamentous bacteria, many of which are thermophilic or
      thermotolerant and commonly found in composts and mouldy fodders, were examined
      for their ability to produce cutinolytic esterase (cutinase) in culture media
      supplemented with cutin, suberin or cutin-containing agricultural by-products.
      Initially, the ability of culture supernatants to hydrolyse the artificial
      substrate p-nitrophenyl butyrate was determined by spectrophotometric assays.
      Only one bacterium, Thermoactinomyces vulgaris NRRL B-16117, exhibited
      cutinolytic esterase production. The enzyme was highly inducible, was repressed
      by the presence of glucose in the medium and hydrolysed both apple and tomato
      cutins. Inducers included apple cutin, apple pomace, tomato peel, potato suberin
      and commercial cork. Unlike similar fungal enzymes, the T. vulgaris cutinolytic
      esterase was not inducible by cutin hydrolysate. The cutinolytic esterase
      exhibited a half-life of over 60 min at 70 degrees C and a pH optimum of >/=
      11.0. This study indicates that thermophylic filamentous bacteria may be
      excellent commercial sources of heat-stable cutin-degrading enzymes that can be
      produced by fermentation of low cost feedstocks.

PMID- 10886610
TI  - Wheat or rye supplemented diets do not affect faecal mucus concentration or the
      adhesion of probiotic micro-organisms to faecal mucus.
AB  - In a crossover study, volunteers consumed a diet supplemented with either wheat
      or rye bread. Levels of faecal mucus were determined and the adhesion of five
      selected probiotics to immobilized intestinal mucus, was assessed. No significant
      difference in the concentration of faecal mucus or adhesion of the probiotics to
      the mucus was observed during the two dietary periods. However, male subjects
      were observed to excrete significantly more mucus during the rye bread
      supplemented diet. From these observations it was concluded that these two diets,
      with a low or high fibre content, did not change the potential binding sites for
      the tested probiotics or affect the level of mucus excreted in the faeces,
      however, on a high fibre diet men excrete more faecal mucus.

PMID- 10886611
TI  - Phylogenetic analysis of rhizosphere-associated beta-subclass proteobacterial
      ammonia oxidizers in a municipal wastewater treatment plant based on
      rhizoremediation technology.
AB  - In wastewater treatment plants based on the rhizosphere zone (rhizoremediation
      technology), ammonia-oxidizing bacteria (AOB) play an important role in the
      removal of fixed nitrogen. However, the diversity of these bacteria in
      rhizoremediation wastewater treatment plants is largely unknown. We employed
      direct PCR amplification and cloning of 16S rRNA genes to determine the
      phylogenetic affiliation of AOB occurring in root and soil samples of a
      wastewater treatment plant (Merzdorf plant, Brandenburg, Germany). 16S rDNA clone
      libraries were screened by hybridization using an oligonucleotide probe specific
      for AOB of the beta subclass of proteobacteria. Comparative sequence analysis of
      all hybridization-positive clones revealed that the majority of rDNA sequences
      was affiliated to members of the genus Nitrosospira and formed a novel subcluster
      (SM cluster), whereas only three sequences were most closely related to
      Nitrosomonas species. Affiliation of the novel Nitrosospira-like sequences with
      those of isolates from soil and rhizosphere suggests that phylogenetic clusters
      reflect physiological differences between members of this genus.

PMID- 10886612
TI  - Relief from glucose interference in microcin B17 biosynthesis by growth in a
      rotating-wall bioreactor.
AB  - Glucose interference in production of microcin B17 by Escherichia coli ZK650 was
      decreased sevenfold by growth in a ground-based rotating-wall bioreactor operated
      in the simulated microgravity mode as compared with growth in flasks. When cells
      were grown in the bioreactor in the normal gravity mode, relief from glucose
      interference was even more dramatic, amounting to a decrease in glucose
      interference of over 100-fold.

PMID- 10886613
TI  - Antimicrobial susceptibility of staphylococci isolated from otitis externa in
      dogs.
AB  - Samples were obtained from 65 unmedicated adult dogs, processed for isolation of
      Staphylococcus species and tested for susceptibility to penicillin G, gentamicin,
      oxacillin, tetracycline, trimethoprim-sulphamethoxazole, streptomycin, ampicillin
      and rifampin. Forty-four isolates were obtained, which represents 67.7% of
      samples. Coagulase-negative species were most commonly found, and the most
      frequently isolated staphylococcus species were Staph. epidermidis and Staph.
      aureus. Other species, such as Staph. simulans, Staph. haemolyticus, Staph.
      saprophyticus and Staph. intermedius were also isolated. Resistance to
      antibiotics was frequently observed, with 90.9% of the isolates showing
      resistance to at least one drug. The most active antimicrobial agents against
      staphylococci isolated from otitis externa of dogs were rifampin and oxacillin.
      Multidrug resistance was a common finding, and one strain of Staph. haemolyticus
      species, was resistant to all tested antimicrobial agents. Resistance to three or
      more different drugs was a common finding, observed in 16 strains (36.4%) of both
      coagulase-positive and coagulase-negative staphylococci. This study highlights
      the emergence of cases of otitis externa determined by coagulase-negative
      staphylococcus strains and once more emphasizes the need for bacterial culture
      with species identification and susceptibility testing of swab specimens from the
      ear canal in order to choose appropriate antimicrobial agents.

PMID- 10886614
TI  - The impact of media composition and petite mutation on the longevity of a
      polyploid brewing yeast strain.
AB  - Ageing in Saccharomyces cerevisiae is a finite phenomenon, determined by
      replicative, rather than chronological lifespan. Yeast physiological condition is
      known to influence industrial fermentation performance, however, until recently
      cellular senescence has not been considered as a brewing yeast stress factor. A
      polyploid lager yeast (BB11) and a brewery isolate, exhibiting petite mutation
      were analysed for longevity. It was observed that mitochondrial deficiency
      induced a reduction in lifespan. In addition, replicative capacity was perceived
      to be dependent on environmental conditions.

PMID- 10886615
TI  - Effect of ionic strength on the inactivation of micro-organisms by microwave
      irradiation.
AB  - Microwave irradiation at 2450 MHz inactivated the cells of Escherichia coli,
      Staphylococcus aureus and Candida albicans suspended in a phosphate buffer. The
      rate of cell inactivation was proportional to that of the increase in temperature
      accompanied by microwave irradiation. The inactivation rates of E. coli and C.
      albicans were affected by addition of NaCl and KCl, but not by sucrose. The
      maximal inactivation effect was exerted at concentrations of 0.5-1.0 mol l-1, and
      the end-point temperature was the highest at the same salt concentrations.
      Correlation of both the electroconductivity and di-electric loss of ionic
      solutions with the heating by microwave irradiation was discussed.

PMID- 10886616
TI  - Antimicrobial susceptibility of bifidobacteria.
AB  - Eighteen Bifidobacterium strains were tested for their susceptibility to a range
      of antimicrobial agents. All the strains tested, including the reference culture
      Lactobacillus acidophilus CH2, were susceptible to several groups of
      antimicrobial agents, they were cephalosporin (cefamandole, cefazolin,
      cefaperazone, cefoxitin), polypeptide (bacitracin), macrolide (erythromycin),
      penicillin (amoxicillin), phenicol (chloramphenicol) and beta-lactam (imipenem).
      Fourteen strains were resistant to more than 10 antibiotics. The reference
      culture was resistant to only three antibiotics. The results showed that
      bifidobacteria are resistant to a wide range of antimicrobial agents.

PMID- 10886617
TI  - Identification of acetic acid bacteria by restriction fragment length
      polymorphism analysis of a PCR-amplified fragment of the gene coding for 16S
      rRNA.
AB  - Acetic acid bacteria (AAB) irreversibly spoil wines and represent a serious
      problem. Limited studies on the ecology of AAB during winemaking have been done
      due to the lack of rapid and precise techniques for their identification. RFLP
      analysis of PCR-amplified fragment of 16S rDNA was performed on AAB reference
      strains. The amplified rDNAs were approximately 870-bp long for all AAB species
      while no amplicons were detected for lactic acid bacteria and yeasts. Out of the
      four restriction enzymes tested, TaqI was the most efficient one and divided the
      studied AAB into six groups. However, complete differentiation among collection
      strains of Acetobacter pasteurianus and Gluconoacetobacter hansenii was not
      possible.

PMID- 10886618
TI  - Growth condition-related response of Listeria monocytogenes 412 to bacteriocin
      inactivation.
AB  - Bacteriocin inactivation of Listeria monocytogenes 412 was studied as a function
      of growth phase. Cells were treated with nisin (300 IU ml-1) or pediocin (320 or
      2560 AU ml-1) for 20 min at 30 degrees C. Inactivation with nisin or the low
      concentration of pediocin was growth phase dependent, with exponentially growing
      cells being more susceptible than stationary cells. No effect of growth phase was
      observed for the high pediocin concentration. Pediocin inactivation (320 AU ml-1)
      of L. monocytogenes 412 exposed to osmotic (6.5% NaCl) or low-temperature (5
      degrees C) stress was investigated. Pediocin failed to inactivate osmotically
      stressed cultures and was unable to inhibit cold-stressed cells to the same
      degree as unstressed cells.

PMID- 10886619
TI  - Effect of uracil on rifamycin SV production by Amycolatopsis mediterranei MV35R.
AB  - The effect of different organic nitrogen compounds on the production of rifamycin
      SV by Amycolatopsis mediterranei MV35R and their optimum concentrations have been
      described. Results obtained indicate that rifamycin SV production increased from
      4020 mg l-1 to 4575 mg l-1 when organic nitrogen compound uracil was added at
      0.2% (w/v) concentration to the fermentation medium by A. mediterranei MV35R. The
      rifamycin SV yield was enhanced by 505 mg l-1 using uracil (2 g l-1) when
      compared with barbital.

PMID- 10886620
TI  - Development of a direct viable count procedure for the investigation of VBNC
      state in Listeria monocytogenes.
AB  - A viable but non-culturable (VBNC) bacterial state was originally detected in
      studies in environmental microbiology. In particular, this state has been
      demonstrated for a number of human pathogens (Escherichia coli, Salmonella
      enteritidis, Vibrio cholerae, Legionella pneumophila and Campylobacter jejuni).
      The presence of VBNC cells poses a major public health problem since they cannot
      be detected by traditional culturing methods and the cells remain potentially
      pathogenic under favourable conditions. But, as far as we know, the VBNC state
      has not been yet described in Listeria monocytogenes. In most studies, this has
      been assessed by the Kogure procedure based on cellular elongation in the
      presence of DNA gyrase inhibitors. The antibiotic used was nalidixic acid in
      order to prevent DNA replication, only efficient in Gram-negative bacteria
      studies. In this study, we describe a new DVC procedure to detect and count
      viable of L. monocytogenes suspended in filtered, sterilized distilled water. We
      used different concentrations of ciprofloxacin, efficient both in Gram-negative
      and Gram-positive bacteria. Bacteria cells were removed and resuspended in BHI
      broth, with yeast extract and ciprofloxacin. The mixture was incubated at
      different incubation times at 37 degrees C. After different incubation times,
      cells were filtered through an isopore polycarbonate black membrane filter and
      covered with a DAPI solution or orange acridine. The filters were prepared and
      examined by epifluorescence microscopy. Elongated cells were counted as viable
      cells, whereas normal size was regarded as nonactive ones. This method allows
      determination of ciprofloxacin concentration and incubation time optimal to
      detect maximum viable cells percentage in L. monocytogenes.

PMID- 10886621
TI  - Adhesion of inactivated probiotic strains to intestinal mucus.
AB  - It has been suggested that probiotics should be viable in order to elicit
      beneficial health effects. Inactivation of probiotics has been suggested to
      interfere with the binding to the mucosa and thereby with the immune modulating
      activity of probiotics. The effect of different inactivation methods on the mucus
      adhesion of nine probiotic strains was studied. Inactivation by heat or gamma
      irradiation generally decreased the adhesive abilities. However, heat treatment
      increased the adhesion of Propionibacterium freudenreichii and gamma-irradiation
      enhanced the adhesion of Lactobacillus casei Shirota. Inactivation by u.v. was
      not observed to modulate the adhesion of the tested strains and it was concluded
      to be the most appropriate method for studying non-viable probiotics and
      preparing control products.

PMID- 10886622
TI  - Cattle tuberculosis schemes: control or eradication?

PMID- 10886623
TI  - In this issue

PMID- 10886624
TI  - Whole doctor education.

PMID- 10886625
TI  - Assessing the evidence in qualitative medical education research.

PMID- 10886626
TI  - What should we do about unreliable scores?

PMID- 10886627
TI  - Community-based medical education: toward the health of the public.

PMID- 10886628
TI  - Collective professional knowledge.

PMID- 10886629
TI  - Faculty mentoring programmes.

PMID- 10886630
TI  - Problem-based learning--time to move forward?

PMID- 10886631
TI  - Problem-based learning--time to step back?

PMID- 10886632
TI  - Prediction of intern attendance at a seminar-based training programme: a
      behavioural intention model.
AB  - CONTEXT: The factors determining intern attendance at 'resident rounds' training
      programmes are not known. AIMS: This study aimed to use a behavioural model (the
      Triandis theory of social behaviour) to predict intern attendance at the resident
      round programme at a metropolitan teaching hospital. SUBJECTS: These included 109
      interns in a large metropolitan teaching hospital, in the 1996 and 1997 cohorts.
      METHODS: Tabulated responses from a structured interview administered to 10
      randomly selected interns were used to develop survey items related to the
      Triandis variables. Attendance was monitored using a sessional logbook and by
      self-report. Item analysis was conducted for each variable scale. Stepwise
      multiple regression models were constructed to predict attendance and intention.
      RESULTS: The average proportion of resident rounds attended was 43% (95%
      confidence intervals (CI) 40-47%) from logbook attendance, and 63% (95% CI 61
      65%) by self-report. Cronbach's alpha for the subscales ranged from 0.62 to 0.91.
      Intern attendance was predicted by the habit of attendance and negatively
      predicted by facilitating conditions (AdjR2=0.26, P<0.0001). The intention to
      attend was only independently predicted by perceived consequences (AdjR2= 0.19, P
      < 0.0001). CONCLUSIONS: The establishment of resident education programmes within
      teaching hospitals requires attention to and modification of facilitating
      conditions that may allow improvements in attendance and in quality of the
      programme.

PMID- 10886633
TI  - Reliability of the amsterdam clinical challenge scale (ACCS): a new instrument to
      assess the level of difficulty of patient cases in medical education.
AB  - INTRODUCTION: In problem-based medical curricula, consideration should be given
      to the level of difficulty of patient cases used for training and assessment. The
      Amsterdam Clinical Challenge Scale (ACCS) has been developed to assess the degree
      of difficulty of patient cases in a systematic and reproducible manner. To
      determine the reliability of the instrument two research questions were
      addressed: (1) How many judges are required, on the basis of the total score of
      the ACCS, to obtain a reliable estimate of the difficulty of a single case? (2)
      How many cases and/or how many judges are needed to reach an acceptable level of
      reliability of the total score of the ACCS? METHOD: Four judges scored 36 patient
      scripts reflecting a wide range of patient problems encountered in general
      practice. Each script was scored four times. In the reliability analysis, the
      generalizability theory was applied. RESULTS: The results show that the judges
      did, indeed, use the whole range of difficulty ratings. When the ACCS is applied
      to a single case, eight or more judges are needed to reach an acceptable level of
      reliability. When more cases are involved, fewer judges are needed; for 10 or
      more cases one judge will be sufficient. CONCLUSIONS: Given the typical length,
      for example of an objective structured clinical examination, the ACCS makes it
      possible to provide a reliable estimate of the level of difficulty of such a test
      with only a limited number of judges.

PMID- 10886634
TI  - The effect on reliability of adding a separate written assessment component to an
      objective structured clinical examination.
AB  - PURPOSE: To determine the effect on test reliability when a separate written
      assessment component is added to an objective structured clinical examination
      (OSCE). METHOD: Volunteers (n=38) from Maastricht Medical School were recruited
      to take a skills-related knowledge test in addition to their regular end-of-year
      OSCE. The OSCE scores of these volunteers did not differ from those of the other
      students of their class. Multivariate generalizability theory was used to
      investigate the combined reliability of the two test formats as well as their
      respective contributions to overall reliability. RESULTS: Combining the two
      formats has an added value. The loss of reliability due to the use of fewer
      stations in the OSCE can be fully compensated by lengthening the written test
      component. CONCLUSION: From the perspective of test reliability, it is possible
      to economize on the resources needed for performance-based assessment by adding a
      separate written test component.

PMID- 10886635
TI  - Benefiting from clinical experience: the influence of learning style and clinical
      experience on performance in an undergraduate objective structured clinical
      examination.
AB  - OBJECTIVE: To assess the relationship between clinical experience, learning style
      and performance in an objective structured clinical examination (OSCE) in medical
      students at the end of their first clinical year. DESIGN: Prospective study of
      undergraduate students taking an OSCE examination at the end of their first
      clinical year. SUBJECTS: 194 undergraduate medical students (95 male). MAIN
      OUTCOME MEASURES: Performance in the OSCE examination, the Entwhistle Learning
      Style Inventory1 and a composite self-reported score of clinical activity during
      the students first clinical year. RESULTS: Performance in the OSCE examination
      was related to well-organized study methods but not to clinical experience. A
      significant relationship between clinical experience and organized deep-learning
      styles suggests that knowledge gained from clinical experience is related to
      learning style. CONCLUSIONS: The relationship between clinical experience and
      student performance is complex. Well-organized and strategic learning styles
      appear to influence the benefits of increased clinical exposure. Further work is
      required to elucidate the most beneficial aspects of clinical teaching.

PMID- 10886636
TI  - Promoting professional knowledge, experiential learning and critical thinking for
      medical students.
AB  - It has been recognized internationally that undergraduate medical education must
      adapt to changing needs, as illustrated by the Tomorrow's Doctors recommendations
      from the General Medical Council. This paper aims to relate contemporary
      educational theory to under-graduate medical educational requirements,
      specifically highlighting conditions (e.g. experiential learning) for:
      professional knowledge acquisition; critical thinking, problem-solving and
      clinical problem-solving; and lifelong professional learning. Furthermore,
      problem-based learning (PBL) is highlighted as potentially providing such
      conditions. There are lessons from contemporary educational theory for the reform
      of undergraduate medical education. These include valuing prior knowledge and
      experience; promoting learner responsibility through facilitating rather than
      directing learning; encouraging learners to test out and apply new knowledge, and
      using small-group work to foster explicitly the elusive skills of critical
      thinking and reflection. Contemporary educational theory contributes valuable
      insights, but cannot dictate the ultimate 'mix'; at best it provides some
      principles for reflective analysis of the learning experiences created for
      tomorrow's doctors.

PMID- 10886637
TI  - The educational challenge of mental health.
AB  - This paper poses a series of fundamental educational challenges about mental
      health. First, it questions whether 'mental health' is a valid concept, in the
      light of debates over mind/body dualism. If the concept is valid, should the
      absence of mental health be seen as an illness, an adaptive strategy or simply a
      statistical eccentricity? Fulford's concept of 'failure of intentional action' is
      commended as a philosophical basis for unravelling these issues. Secondly, the
      paper considers whether diagnosis is a simple or complex process, and whether it
      can be an objective activity or one which involves a strong subjective element.
      The current and potential value of multiaxial classification systems are
      discussed. Thirdly, themes concerning mental health treatment are introduced,
      covering problems with consent and patient preference, the evidential basis of
      interventions, and the range and limitations of possible treatments. Finally, the
      paper reviews the educational processes needed to meet these challenges
      effectively. It recommends the development of multifaceted educational
      programmes, nurturing a spirit of critical enquiry and personal awareness and,
      above all, the recognition and toleration of the uncertainty and complexity which
      lie at the heart of successful medical practice.

PMID- 10886638
TI  - The integration ladder: a tool for curriculum planning and evaluation.
AB  - Integration has been accepted as an important educational strategy in medical
      education. Discussions about integration, however, are often polarized with some
      teachers in favour and others against integrated teaching. This paper describes
      11 points on a continuum between the two extremes. * Isolation * Awareness *
      Harmonization * Nesting * Temporal co-ordination * Sharing * Correlation *
      Complementary * Multi-disciplinary * Inter-disciplinary * Trans-disciplinary As
      one moves up the ladder, there is less emphasis on the role of disciplines, an
      increasing requirement for a central curriculum, organizational structure and a
      requirement for greater participation by staff in curriculum discussions and
      planning. The integration ladder is a useful tool for the medical teacher and can
      be used as an aid in planning, implementing and evaluating the medical
      curriculum.

PMID- 10886639
TI  - The parallel rural community curriculum: an integrated clinical curriculum based
      in rural general practice.
AB  - INTRODUCTION: In an attempt to address the rural medical workforce
      maldistribution and the concurrent inappropriate caseload at the urban tertiary
      teaching hospitals, Flinders University and the Riverland Division of General
      Practice decided to pilot, in 1997, an entire year of undergraduate clinical
      curriculum in Australian rural general practice. This program is called the
      Parallel Rural Community Curriculum (PRCC). This paper is a discussion of the
      aims of the programme; student selection; practice recruitment; curriculum
      structure, and academic content, together with lessons learnt from the evaluation
      of the first cohort of students' experience of the course. METHODS: Independent
      external evaluators undertook a thematic analysis of a series of structured
      interviews of students and faculty involved in both the PRCC and the traditional
      curriculum. The mean examination results were determined and a rank order
      comparison of student academic performance was undertaken. RESULTS: The eight
      selected volunteer students reported greater access to patients and clinical
      learning opportunities than their mainstream counterparts and learned clinical
      decision making in the context of the whole patient, their family, and the
      available community resources. They identified patients with 'core' clinical
      conditions and had a longitudinal exposure to common diseases, whereas hospital
      based peers had a cross-sectional exposure to highly filtered illness. The PRCC
      students' academic performance improved in comparison with that of their tertiary
      hospital peers' and in comparison to their own results in previous years.
      CONCLUSION: The PRCC curriculum has cut across the traditional clinical
      discipline boundaries by teaching in an integrated way in rural general practice.
      It has affirmed the potential role of true generalist physicians in undergraduate
      medical education.

PMID- 10886640
TI  - Defining the content for the objective structured clinical examination component
      of the professional and linguistic assessments board examination: development of
      a blueprint.
AB  - INTRODUCTION: We describe the steps taken to develop an appropriate list of
      'clinical problems' used to define the content of the objective structured
      clinical examination (OSCE) component of the Professional and Linguistic
      Assessments Board (PLAB) examination. METHOD: A blueprint and list of 255
      clinical problems was compiled by reviewing PLAB questions, published curricula
      of the UK Royal Colleges and other sources such as the General Medical Council's
      own guidelines. This list was sent to a random sample of 251 successful PLAB
      candidates who were asked to rate the clinical problems using a scale of 'seen
      frequently/seldom/never' and to 120 members of the accident and emergency (A&E)
      specialists' association who were asked to identify 'important' tasks. The list
      was further validated using activity data obtained for consecutive A&E
      attendances (934) and admissions (6130) at three hospitals. RESULTS: After two
      mailings, 131/251 (52%) former PLAB candidates and 89/120 (74%) A&E specialists
      replied. All of the 255 clinical problems were seen by some former candidates and
      were felt to be important by some A&E specialists. Of the 255 problems, 40 were
      neither rated as important nor as seen frequently/seldom by over 50% of
      respondents. The 255 clinical problems covered a mean 94% consecutive A&E
      attendances and 97.6% reasons for hospital admission. The correlation between
      clinical problems that were frequently encountered and those felt to be important
      was rho=0.38 (P<0.01). CONCLUSION: The clinical problems appear to be appropriate
      for defining the content of the PLAB OSCE. We suggest that our problem list is
      useful in that all the problems are seen by some senior house officers, are felt
      to be important by some A&E specialists and cover greater than or equal to 94% of
      the conditions for which patients both attend and are admitted from casualty. The
      correlation between clinical task importance and the frequency that they were
      seen was only moderate, partly reflecting the relative seriousness of some
      uncommon medical conditions, which should not be missed on clinical assessment.
      The content of the OSCE component of the PLAB examination is being reviewed in
      the light of the findings of this study. The limitations of the study are
      discussed.

PMID- 10886641
TI  - Formative assessment of the consultation performance of medical students in the
      setting of general practice using a modified version of the leicester assessment
      package.
AB  - OBJECTIVE: To evaluate the use of a modified version of the Leicester Assessment
      Package (LAP) in the formative assessment of the consultation performance of
      medical students with particular reference to validity, inter-assessor
      reliability, acceptability, feasibility and educational impact. DESIGN: 180 third
      and fourth year Leicester medical students were directly observed consulting with
      six general practice patients and independently assessed by a pair of assessors.
      A total of 70 practice and 16 departmental assessors took part. Performance
      scores were subjected to generalizability analysis and students' views of the
      assessment were gathered by questionnaire. RESULTS: Four of the five categories
      of consultation performance (Interviewing and history taking, Patient management,
      Problem solving and Behaviour and relationship with patients) were assessed in
      over 99% of consultations and Physical examination was assessed in 94%. Seventy
      six percent of assessors reported that the case mix was 'satisfactory' and 20%
      that it was 'borderline'; 85% of students believed it to have been satisfactory.
      Generalizability analysis indicates that two independent assessors assessing the
      performance of students across six consultations would achieve a reliability of
      0.94 in making pass or fail decisions. Ninety-eight percent of students perceived
      that their particular strengths and weaknesses were correctly identified, 99%
      that they were given specific advice on how to improve their performance and 98%
      believed that the feedback they had received would have long-term benefit.
      CONCLUSIONS: The modified version of the LAP is valid, reliable and feasible in
      formative assessment of the consultation performance of medical students.
      Furthermore, almost all students found the process fair and believed it was
      likely to lead to improvements in their consultation performance. This approach
      may also be applicable to regulatory assessment as it accurately identifies
      students at the pass/fail margin.

PMID- 10886642
TI  - Teaching medical students about over-the-counter medications.
AB  - OBJECTIVES: Over-the-counter (OTC) medications account for over half of US drug
      expenses but have received little attention in medical school education. This
      pilot study evaluated student attitudes and knowledge in connection with a new
      curriculum in an ambulatory teaching clinic. DESIGN: Learning objectives were
      developed for six categories of OTC medications and students taught each other
      under the direction of a clinical pharmacist and family physician. Learning was
      undertaken in small groups and a site visit to a pharmacy was included. A 25
      question test of knowledge was administered before and 6 months after the
      project, and student attitudes were assessed. SETTING: The sessions were taught
      as part of a longitudinal family medicine clerkship at an ambulatory care
      teaching clinic, Rockford, Illinois, USA. SUBJECTS: Twenty third-year medical
      students took the pre-test and attended the educational sessions; 19 completed
      the post-test and 16 completed the attitudinal survey. RESULTS: The mean pre-test
      score of 49% improved to 67% on the post-test (p<0.001). On the survey, 94% found
      the material useful and 88% liked the small group learning, but only 60% felt the
      pharmacy trip was worthwhile. CONCLUSION: In this study, medical students found
      teaching about OTC medications to be useful and showed significant improvement on
      a fund of knowledge test.

PMID- 10886643
TI  - Richard reznick

PMID- 10886645
TI  - Validity of written tests Author's reply

PMID- 10886644
TI  - Validity of written tests.

PMID- 10886646
TI  - Effect of an early rural placement on later elective choices of medical students.

PMID- 10886647
TI  - Conservation genetics of bush mango from central/west Africa: implications from
      random amplified polymorphic DNA analysis.
AB  - Genetic variation was assessed in the two bush mango species, Irvingia gabonensis
      and I. wombolu, valuable multipurpose fruit trees from central and west Africa
      that are currently undergoing domestication. A total of 130 individuals sampled
      from Cameroon, Nigeria and Gabon were analysed using 74 random amplified
      polymorphic DNAs (RAPDs). Significant genetic integrity was found in the two
      morphologically similar species (among-species analysis of molecular variance
      [AMOVA] variance component 25.8%, P < 0.001), with no evidence of hybridization,
      even between individuals from areas of sympatry where hybridization was
      considered probable. Results suggest that large-scale transplantation of either
      species into new habitats will probably not lead to genetic introgression from or
      into the other species. Therefore, subsequent cultivation of the two species
      should not be hindered by this consideration, although further studies on the
      potential for hybridization/introgression between these species would be prudent.
      Significant genetic differentiation of both species (among-countries within
      species, nested AMOVA variance component 9.8%, P < 0.001) was observed over the
      sampled regions, and genetic similarity of samples decreased significantly with
      increasing geographical distance, according to number of alleles in common (NAC)
      analysis. 'Hot spots' of genetic diversity were found clustered in southern
      Nigeria and southern Cameroon for I. wombolu, and in southern Nigeria, southern
      Cameroon and central Gabon for I. gabonensis. The possible reasons for this
      distribution of genetic variation are discussed, but it may reflect evolutionary
      history, as these populations occur in areas of postulated Pleistocene refugia.
      The application of these results to domestication programmes and, in the light of
      extensive deforestation in the region, conservation approaches, is discussed.

PMID- 10886648
TI  - Effects of natural selection on patterns of DNA sequence variation at the
      transferrin, somatolactin, and p53 genes within and among chinook salmon
      (Oncorhynchus tshawytscha) populations.
AB  - This paper describes DNA sequence variation within and among four populations of
      chinook salmon (Oncorhynchus tshawytscha) at the transferrin, somatolactin and
      p53 genes. Patterns of variation among salmon species at the transferrin gene
      have been hypothesized to be shaped by positive natural selection for new alleles
      because the rate of nonsynonymous substitution is significantly greater than the
      rate of synonymous substitution. The twin goals of this study were to determine
      if the history of selection among salmon species at the transferrin gene is also
      reflected in patterns of intraspecific variation in chinook salmon, and to look
      for evidence of local adaptation at the transferrin gene by comparing patterns of
      nonsynonymous and synonymous variation among chinook salmon populations. The
      analyses presented here show that unlike patterns of variation between species,
      there is no evidence of greater differentiation among chinook salmon populations
      at nonsynonymous compared to synonymous sites. There is also no evidence of a
      reduction of within-species variation due to the hitchhiking effect at the
      transferrin gene, although in some populations nonsynonymous and synonymous
      derived mutations are both at higher frequencies than expected under a simple
      neutral model. Population size weighted selection coefficients (4Ns) that are
      consistent with both the inter and intraspecific data range from approximately 10
      to approximately 235, and imply that between 1 and 40% of new nonsynonymous
      mutations at the transferrin gene have been beneficial.

PMID- 10886649
TI  - The colonization history of Olea europaea L. in Macaronesia based on internal
      transcribed spacer 1 (ITS-1) sequences, randomly amplified polymorphic DNAs
      (RAPD), and intersimple sequence repeats (ISSR).
AB  - Phylogenetic relationships in the Olea europaea complex and the phylogeography of
      24 populations of the Macaronesian olive (O. europaea ssp. cerasiformis) were
      assessed by using three molecular markers: nuclear ribosomal internal transcribed
      spacer 1 (ITS-1) sequences, randomly amplified polymorphic DNAs (RAPD), and
      intersimple sequence repeats (ISSR). Parsimony analysis of the ITS-1 sequences
      and Neighbour-joining (NJ) analyses of RAPD and ISSR banding variation revealed
      four major lineages in the O. europaea complex: (1) ssp. cuspidata; (2) ssp.
      cerasiformis from Madeira; (3) ssp. laperrinei; and (4) ssp. cerasiformis from
      the Canary Islands plus ssp. europaea. These results provide unequivocal support
      for two independent dispersal events of Olea to the Madeira and Canary Islands.
      Molecular and morphological evidence led to recognition of two separate olive
      taxa in Macaronesia, to date included in ssp. cerasiformis. NJ analyses of the
      combined RAPD and ISSR data suggest that the colonization of the Canaries by O.
      europaea may have followed an east to west stepping-stone model. An interisland
      dispersal sequence can be recognized, starting from the continent to
      Fuerteventura, Gran Canaria, Tenerife, La Gomera, and finally La Palma. High
      dispersal activity of the lipid-rich Olea fruits by birds in the Mediterranean
      region is congruent with multiple dispersal of olives to Macaronesia and
      successive colonization of the archipelagos. The observation of strong genetic
      isolation between populations of different islands of the Canary Islands
      suggests, however, that subsequent interisland dispersal and establishment has
      been very rare or may not have occurred at all.

PMID- 10886650
TI  - Genetic analysis of the mating system of the common brushtail possum (Trichosurus
      vulpecula) in New Zealand farmland.
AB  - We examined male reproductive success in a common brushtail possum population in
      New Zealand farmland. Paternity was assigned to 66 of 91 pouch young (maternity
      known), using a likelihood approach applied to genotypes at six microsatellite
      loci having an overall average exclusion probability of around 99%. The
      distribution of number of offspring per male was L-shaped with a standardized
      variance of 1.52. At least 46% of the 76 sampled reproductively mature males,
      bred, siring between one and four offspring each. Although breeding males were on
      average older and larger than nonbreeding males, the small differences did not
      result in a significant overall difference between the two groups in a
      multivariate permutation test analagous to a t-test. Paternity analysis of 22
      sibling pairs (resulting from experimental removal of pouch young early in the
      breeding season, inducing a second oestrous) suggested that sequential mating of
      females with the same male was uncommon ( approximately 16-27%). Whilst there was
      a tendency for female possums to mate with nearby males, consistent with previous
      observations of territorial mating behaviour in Australian populations, some
      interhabitat matings were also inferred. The study population displayed only a
      low degree of polygyny, which may in part reflect population and habitat
      characteristics of the study site. A comprehensive understanding of the mating
      system of Trichosurus vulpecula awaits genetic paternity analysis in additional
      populations from both Australia and New Zealand, using quantitative approaches
      undertaken in this study.

PMID- 10886651
TI  - Effect of crop rotation and soil cover on alteration of the soil microflora
      generated by the culture of transgenic plants producing opines.
AB  - The culture of transgenic Lotus corniculatus plants producing opines, which are
      bacterial growth substrates, leads to the selection of rhizospheric bacteria able
      to utilize these substrates. We have investigated the fate of the opine-utilizing
      community over time under different experimental conditions following elimination
      of selective pressure exerted by the transgenic plants. These plants were removed
      from the soil, which was either left unplanted or replanted with wild-type L.
      corniculatus or wheat plants. The density of opine-utilizing bacteria in the
      fallow soils remained essentially unchanged throughout the experiment, regardless
      of the soil of origin (soil planted with wild-type or transgenic plants). When
      wild-type Lotus plants were used to replace their transgenic counterparts, only
      the bacterial populations able to utilize the opines were affected. Long-term
      changes affecting the opine-utilizing bacterial community on Lotus roots was
      dependent upon the opine studied. The concentration of nopaline utilizers
      decreased, upon replacement of the transgenic plants, to a level similar to that
      of normal plants, while the concentration of mannopine utilizers decreased to
      levels intermediate between transgenic and normal plants. These data indicate
      that: (i) the opine-utilizing bacterial populations can be controlled in the
      rhizosphere via plant-exudate engineering; (ii) the interaction between the
      engineered plants and their root-associated micro-organisms is transgene
      specific; and (iii) alterations induced by the cultivation of transgenic plants
      may sometimes be persistent. Furthermore, opine-utilizing bacterial populations
      can be controlled by crop rotation. Therefore, favouring the growth of a
      rhizobacterium of agronomic interest via an opine-based strategy appears
      feasible.

PMID- 10886652
TI  - Mitochondrial DNA variation in the hybridizing fire-bellied toads, Bombina
      bombina and B. variegata.
AB  - Using five restriction enzymes, geographical variation of mitochondrial DNA
      (mtDNA) in Bombina bombina and B. variegata was studied in samples from 20
      locations. Each restriction enzyme produced a species-specific fragment pattern.
      B. bombina haplotypes A and B were closely related to each other. In contrast,
      haplotypes A and B of B. variegata formed two distinct lineages. A very
      distinctive haplotype (C) was found in the Carpathian Mountains, whereas two
      other haplotypes, D and E (differing by a single AvaI site), were present in
      western Europe and the Balkans, respectively. Populations polymorphic for
      haplotypes D and E occurred in the central Balkans where the haplotypes could
      replace each other clinally. mtDNA sequence divergence between B. bombina and B.
      variegata was estimated as 6.0-8.1% and 4.7-5.2% between type C and types D/E of
      B. variegata. The latter divergence is contrary to allozyme and morphological
      data that place the western and Carpathian B. v. variegata together (Nei's D =
      0.07) and separate them from the Balkan subspecies B. v. scabra (Nei's D = 0.18).
      Broad interspecific correlation among morphology, allozymes and mtDNA types in
      European fire-bellied toads argues that, despite continuous hybridization
      (interrupted perhaps during Pleistocene glacial maxima), little or no mtDNA
      introgression between the species has occurred outside the narrow hybrid zones
      that separate these parapatric species.

PMID- 10886653
TI  - Clonal structure in a dwarf bamboo (Sasa senanensis) population inferred from
      amplified fragment length polymorphism (AFLP) fingerprints.
AB  - Amplified fragment length polymorphism (AFLP) fingerprints were used to reveal
      clonal structure of a dense population of dwarf bamboo, Sasa senanensis, in a 10
      ha study plot at Sugadaira Montane Research Center, University of Tsukuba,
      Nagano, Japan. We generated AFLP fingerprints for 51 leaf samples, collected at
      50 m intervals, using three selective primer pairs. A total of 135-166 fragments
      were detected per sample, and 22 different fingerprints were identified based on
      24-83 differing fragments. Our results demonstrate that the S. senanensis
      population in our plot consists of at least 22 clones and that the largest single
      clone occurs over a distance of about 300 m. Furthermore, the clone distribution
      pattern implies a relationship between site quality and clonal structure.

PMID- 10886654
TI  - Hybrid origins of honeybees from italy (Apis mellifera ligustica) and sicily (A.
      m. sicula).
AB  - The genetic variability of honeybee populations Apis mellifera ligustica, in
      continental Italy, and of A. m. sicula, in Sicily, was investigated using nuclear
      (microsatellite) and mitochondrial markers. Six populations (236 individual bees)
      and 17 populations (664 colonies) were, respectively, analysed using eight
      microsatellite loci and DraI restriction fragment length polymorphism (RFLP) of
      the cytochrome oxidase I (COI)-cytochrome oxidase II (COII) region.
      Microsatellite loci globally confirmed the southeastern European heritage of both
      subspecies (evolutionary branch C). However, A. m. ligustica mitochondrial DNA
      (mtDNA) appeared to be a composite of the two European (M and C) lineages over
      most of the Italian peninsula, and only mitotypes from the African (A) lineage
      were found in A. m. sicula samples. This demonstrates a hybrid origin for both
      subspecies. For A. m. ligustica, the most widely exported subspecies, this hybrid
      origin has long been obscured by the fact that in the main area of queen
      production (from which most of the previous ligustica bee samples originated) the
      M mitochondrial lineage is absent, whereas it is present almost everywhere else
      in Italy. This presents a new view of the evolutionary history of European
      honeybees. For instance, the Iberian peninsula was considered as the unique
      refuge for the M branch during the quaternary ice periods. Our results show that
      the Apennine peninsula played a similar role. The differential distribution of
      nuclear and mitochondrial markers observed in Italy seems to be a general feature
      of introgressed honeybee populations. Presumably, it stems from the social nature
      of the species in which both genome compartments are differentially affected by
      the two (individual and colonial) reproduction levels.

PMID- 10886655
TI  - Delineation of genetic zones in the European Norway spruce natural range:
      preliminary evidence.
AB  - We applied geostatistics to previously reported chloroplast simple sequence
      repeats (cpSSR) haplotype frequency data from 95 European Norway spruce
      populations to provide preliminary evidence about the following issues: (i)
      delineation of genetically homogeneous regions ('genetic zones'); (ii) prediction
      of their haplotype frequencies and definition of related criteria to be applied
      for provenance identification and certification of seedlots; (iii) identification
      of putative allochthonous stands; and (iv) construction of a continental-scale
      'availability map' of the intraspecific biodiversity for Norway spruce. Direct
      evidence of large-scale geographical structure over the European natural range
      was obtained, detecting both geographical clines and stationary patterns. The
      increase of the mean genetic divergence by geographical distance (up to
      approximately 1800 km apart) provided a strong hint that geographical distance is
      a major factor of differentiation in Norway spruce. Haplotype frequency surfaces
      were obtained by applying ordinary kriging to sampling frequency data. Cluster
      analysis carried out on haplotype frequency surfaces revealed a fair
      discrimination among 16 genetic zones, with an accuracy of 0.916. Dendrogram
      analysis carried out on the predicted mean haplotype frequency confirmed a fairly
      good separability of the genetic zones detected. Reclassification of populations
      by discriminant analysis confirmed the robustness of the genetic subdivision
      obtained. Combining the information from discriminant analysis and cross
      validation of sampling points, three populations likely to be of nonlocal origin
      were identified. The application of geostatistical analysis to genetic marker
      data is discussed in relation to breeding activities and to the formulation of
      appropriate conservation strategies.

PMID- 10886656
TI  - Microdiversity of uncultured marine prokaryotes: the SAR11 cluster and the marine
      Archaea of Group I.
AB  - The SAR11 cluster and the Group I of marine Archaea represent probably the best
      two examples of uncultured marine prokaryotes of widespread occurrence. To study
      their microdiversity and distribution, a total of 81 and 48 clones, respectively,
      were sequenced from Mediterranean and Antarctic waters at different locations and
      depths. The DNA regions chosen for the analysis were the last third,
      approximately, of the 16S rRNA gene and the 16S-23S intergenic spacer (also known
      as internal transcribed spacer [ITS]). There was a high concordance in both, even
      with the extremely variable ITS, where potential probes have been proposed for
      the identification and isolation of these micro-organisms. In terms of community
      structure, our results show that although depth-related factors seem to be
      predominant in the final associations of the clones, geography also plays a
      significant role. A major group of surface-associated sequences was found in both
      SAR11 and marine Archaea. In both cases this group was relatively homogeneous
      containing little diversity in terms of sequence, while sequences retrieved from
      deep samples and some surface clones contained much more heterogeneity. As a
      whole, both groups of prokaryotes seem to fall within the limits of well-defined
      taxonomic units.

PMID- 10886657
TI  - Population structure of long-finned pilot whales in the North Atlantic: a
      correlation with sea surface temperature?
AB  - The long-finned pilot whale, Globicephala melas, is a social, pelagic odontocete
      distributed widely in the cold temperate waters of the North Atlantic. Despite
      genetic, morphometric, physiological and observational studies, it remains
      unclear whether any population substructure exists. We have used eight highly
      polymorphic microsatellite loci to analyse samples from four disparate sampling
      sites: USA East Coast (Cape Cod), West Greenland, the Faeroe Islands and the UK.
      Our results indicate that substructure does exist, and is particularly pronounced
      between West Greenland and other sites. The magnitudes of the various pairwise
      comparisons do not support a simple isolation-by-distance model. Instead, the
      patterns of genetic differentiation suggest that population isolation occurs
      between areas of the ocean which differ in sea surface temperature. Such a
      mechanism is supported by the observation that temperature is a primary factor
      determining the relative distributions of two short-finned pilot whale (G.
      macrorhynchus) populations off the Pacific coast of Japan.

PMID- 10886658
TI  - Genetic variation and structure in six Rhododendron species (Ericaceae) with
      contrasting local distribution patterns in Hong Kong, China.
AB  - Genetic variability of six rhododendrons with contrasting local distribution
      patterns in Hong Kong was assessed by starch gel electrophoresis. Rhododendron
      championiae, R. hongkongense and R. simiarum are locally rare with disjunct
      distributions, R. moulmainense is restricted and R. farrerae and R. simsii are
      common. For each species, 13-18 allozyme loci representing 12-16 enzyme systems
      were scored. The six species showed similar levels of genetic variations (HT
      ranged from 0.209 to 0.386 and AT ranged from 2.4 to 4.1) which are high compared
      to plants with similar life history traits. Genetic structure, in contrast,
      varied greatly between species, with FST ranging from 0.056 to 0.393. The three
      rarest species had high genetic differentiation (FST and FPT) and distinct
      geographical patterns, while the other three had low differentiation and little
      or no geographical structure. These differences are attributed to both present
      distributions and historical changes following deforestation within the last 1000
      years. The conservation implications of these results are discussed.

PMID- 10886659
TI  - Hydrography and population genetic structure in brook charr (Salvelinus
      fontinalis, Mitchill) from eastern Canada.
AB  - Despite the abundance of studies of genetic diversity in freshwater fishes, few
      have specifically addressed the role of habitat structure in partitioning genetic
      variance within and among populations. In this study, we analysed the variability
      of six microsatellite loci among 24 brook charr population samples in order to
      correlate hydrographic structure with genetic organization. These populations
      originated from three Canadian National parks (Kouchibouguac, Fundy and Forillon)
      that showed distinct hydrographic structure. Considering the general
      characteristics of these habitats, we formulated specific hypotheses in regard to
      genetic structure, which were principally based on the potential for gene flow
      and population size associated with each habitat. The hierarchical analysis of
      molecular variance and the genetic distances computed among populations revealed
      that habitat structure analyses constitute an important, but insufficient,
      predictor of genetic structure. We discuss the importance of habitat complexity
      on genetic structure in the context of management and conservation.

PMID- 10886660
TI  - A direct regional scale estimate of transgene movement from genetically modified
      oilseed rape to its wild progenitors.
AB  - One of the major environmental concerns over genetically modified (GM) crops
      relates to transgene movement into wild relatives. The pattern of hybridization
      ultimately affects the scale and rapidity of ecological change and the
      feasibility of containment. A new procedure for quantifying hybrid formation over
      large areas is described. Remote sensing was used to identify possible sites of
      sympatry between Brassica napus and its progenitor species across 15 000 km2 of
      south-east England in 1998. Two sympatric populations with B. rapa and one with
      B. oleracea were found over the entire survey area. Every newly recruited plant
      in these populations in 1999 was screened for hybrid status using flow cytometry
      and molecular analyses. One hybrid was observed from the 505 plants screened in
      the B. rapa populations but none of the nine B. oleracea recruits were hybrids.
      Measures to minimize gene flow are suggested, and a procedure for the post
      release evaluation and containment of GM cultivars is proposed.

PMID- 10886661
TI  - Isolation and characterization of polymorphic microsatellite markers in Abudefduf
      luridus (Pisces: Pomacentridae).

PMID- 10886662
TI  - Microsatellite markers for the European Roe deer (Capreolus capreolus).

PMID- 10886663
TI  - Isolation and characterization of microsatellite loci in the yellow perch (Perca
      flavescens), and cross- species amplification within the family Percidae.

PMID- 10886664
TI  - Isolation of microsatellite markers in the digenetic trematode Schistosoma
      mansoni from Guadeloupe island.

PMID- 10886665
TI  - Ten microsatellite loci isolated and developed for the blackspot seabream,
      Pagellus bogaraveo (Brunnich 1768).

PMID- 10886666
TI  - Characterization of highly variable microsatellite loci in the bat Myotis myotis
      (Chiroptera: Vespertilionidae).

PMID- 10886667
TI  - Polymorphic variable number of tandem repeat (VNTR) loci in the ommastrephid
      squid, Illex coindetii and Todaropsis eblanae.

PMID- 10886668
TI  - Polymorphic microsatellite DNA loci identified in the African elephant (Loxodonta
      africana).

PMID- 10886669
TI  - Microsatellite variation in the freshwater snail Biomphalaria pfeifferi.

PMID- 10886670
TI  - Rapid isolation and characterization of microsatellites from the genome of Asian
      arowana (Scleropages formosus, Osteoglossidae, Pisces).

PMID- 10886671
TI  - Microsatellite variation in the freshwater schistosome-transmitting snail
      Biomphalaria glabrata.

PMID- 10886672
TI  - Nitrergic and cholinergic vagal pathways involved in the regulation of canine
      proximal gastric tone: an in vivo study.
AB  - To better understand the relationship between cholinergic and nitrergic (NO)
      innervation in the regulation of proximal gastric (fundic) tone in vivo, the
      effects of nitric oxide synthase blockade on fundic tone were studied in
      conscious dogs using vagal cooling and an electronic barostat. Vagal cooling,
      atropine (0.05 mg kg-1 i. v. bolus) and hexamethonium (1 mg kg-1 i.v. bolus) all
      markedly decreased fundic tone as reflected by increased intragastric volume,
      indicating a significant contribution of vagal and enteric cholinergic pathways
      to the maintenance of canine fundic tone. Administration of L-NNA (10 mg kg-1
      i.v. bolus) increased fundic tone and the effects of L-NNA were completely
      prevented by prior vagal cooling or atropine administration, but not by
      pretreatment with hexamethonium. The relaxation effects of neurally derived NO
      appear primarily related to inhibition of ongoing vagal cholinergic activity. The
      data are consistent with the primary site of action of nitrergic mechanisms on
      gastric fundic tone in conscious dogs being at a presynaptic site on vagal
      cholinergic efferent nerves.

PMID- 10886673
TI  - Evidence for functional NK1-tachykinin receptors on motor neurones supplying the
      circular muscle of guinea-pig small and large intestine.
AB  - The guinea-pig intestine was investigated to determine which neurones are excited
      via NK1 receptors. The specific NK1 receptor agonists [Sar9, Met(O2)11]-SP and
      septide contracted the circular muscle of all regions via a tetrodotoxin (TTX)
      insensitive mechanism. In the proximal colon, they also evoked a TTX-sensitive
      relaxation; in the distal colon, the contractions were larger when nerve impulses
      were blocked with TTX, indicating that the agonists excited inhibitory motor
      neurones. In the duodenum and ileum, TTX reduced agonist-evoked contractions
      indicating that excitatory motor neurones were activated. In the presence of
      indomethacin, TTX enhanced contractions of ileal circular muscle evoked by these
      agonists suggesting that NK1 receptors were on inhibitory motor neurones.
      Blockade of nitric oxide synthase (NOS) enhanced NK1 receptor agonist evoked
      contractions of duodenal circular muscle, indicating that the agonists excite
      inhibitory motor neurones in duodenum. Neurones immunoreactive for NK1 receptors
      were studied in the duodenum and distal colon. As reported previously for the
      ileum, 1 some neurones were immunoreactive for NOS and had Dogiel type I
      morphology; features characteristic of inhibitory motor neurones. In conclusion,
      there are functional NK1 receptors on excitatory and inhibitory motor neurones in
      the guinea-pig small intestine and on inhibitory motor neurones in the colon.

PMID- 10886674
TI  - Arginosuccinate synthetase, arginosuccinate lyase and NOS in canine
      gastrointestinal tract: immunocytochemical studies.
AB  - Nitric oxide synthase (NOS) requires the substrate L-arginine for NO production
      to support multiple gastrointestinal functions. We asked, 'Where do enzymes to
      regenerate L-arginine from L-citrulline exist?'. We examined loci of
      immunoreactivities in the canine gastrointestinal tract for arginosuccinate
      synthetase and arginosuccinate lyase, enzymes that resynthesize L-arginine from L
      citrulline, in relation to the distribution of nNOS immunoreactivity or NADPH
      diaphorase histochemistry. Arginosuccinate synthetase and lyase were present in
      many neurones and nerve fibres in the myenteric plexus of the lower oesophageal
      sphincter (LOS), antrum, pylorus, ileum and colon; in the submucosal plexus of
      ileum and colon; in longitudinal muscle of ileum and colon; and in nerve bundles
      in circular muscle everywhere. LOS muscle was also immunoreactive for both
      enzymes. Circular and longitudinal muscle cells of the ileum and colon and cells
      resembling interstitial cells of Cajal in the deep muscular plexus of the ileum
      and the submuscular plexus of the colon also appeared immunoreactive. In
      neurones, arginosuccinate synthetase and nNOS were usually co-localized. NADPH
      diaphorase activity was present in LOS and likely in pylorus, but not in
      muscularis externa of ileum or colon. We conclude that resynthesis of L-arginine
      probably occurs in enteric nerves, interstitial cells of Cajal (ICC) and LOS
      muscle; also apparently in some cells without NOS to utilize it.

PMID- 10886675
TI  - A scintigraphic study of oropharyngeal swallowing dynamics in Chagas' disease.
AB  - We studied oropharyngeal function in patients with Chagas' disease and
      oesophageal disease. Twenty-four patients with Chagas' disease, 17 of them with
      oesophageal disease, were submitted to scintigraphic oropharyngeal transit. A
      single swallow of a 10-mL bolus of water labelled with 40 MBq 99m Tc-phytate,
      followed by image acquisition at 20 images s-1 yielded time-activity curves in
      which oropharyngeal dynamics was evaluated. Thirteen normal volunteers were used
      as controls. Oral transit was longer for chagasics with oesophageal disease than
      for controls (P=0.004) or for chagasics with a normal oesophagus (P=0.028).
      Oesophageal filling rate, measured by the slope of the ascending aspect of the
      oesophageal radioactivity curve, was lower for chagasics with oesophageal disease
      than for controls (P=0.037). Also, maximum oesophageal filling rate was lower
      (P=0. 021) and occurred later (P=0.003) for chagasics with oesophageal disease
      than for controls. Pharyngeal clearance was positively correlated with oral
      transit (r=0.603, P=0.002). We conclude that chagasic oesophageal disease is
      associated with oral transit delay and a slower oesophageal filling rate.

PMID- 10886676
TI  - Neuropeptide Y in the paraventricular nucleus of the hypothalamus stimulates
      colonic transit by peripheral cholinergic and central CRF pathways.
AB  - There is evidence suggesting that neuropeptide Y (NPY) as well as corticotropin
      releasing factor (CRF) in the paraventricular nucleus of the hypothalamus (PVN)
      are involved in the CNS regulation of gastrointestinal (GI) function. We studied
      the effects of NPY or Y1-and Y2-receptor agonists microinjected into the PVN on
      colonic transit. Microinjection of NPY into the PVN at doses of 0.15-1.5 microg
      decreased the colonic transit time of conscious rats up to 49%. Pretreatment with
      the peripherally acting cholinergic antagonist atropine methyl nitrate (0.1 mg kg
      1 i.p.) blocked the NPY into PVN-induced effect on colonic motor function.The
      agonist of the Y1-receptor, NPY(Leu31, Pro34), as well as the Y2-receptor
      agonist, NPY(13-36), dose-dependently decreased colonic transit time when
      microinjected into the PVN (0.05, 0.15 and 0.5 microg). However, the Y1-receptor
      agonist was more effective. Intracerebroventricular (ICV) application of the CRF
      receptor antagonist, alpha-helical-CRF9-41 (50 microg/rat), blocked the NPY
      effect in the PVN on colonic motor function. In conclusion, stimulation of
      colonic transit by NPY acting in the PVN was observed. The PVN is more sensitive
      to agonists acting on the Y1- than on the Y2-receptor to mediate stimulation of
      propulsive colonic motility. The effect of NPY in the PVN on colonic motor
      function depends on central CRF and peripheral cholinergic pathways.

PMID- 10886677
TI  - The effect of mechanoreceptor stimulation of the laryngopharynx on the oesophago
      gastric junction.
AB  - Stimulation of the pharynx by injection of minute amounts of water induces
      prolonged period of lower oesophageal sphincter (LOS) relaxation and augmentation
      of the crural diaphragm (CD) contraction. The purpose of this study was to
      determine the effects of stimulating mechano-receptors at the laryngopharynx on
      the LOS and CD by using an air pulse stimulation device. Air pulses were
      delivered via the internal channel of a flexible endoscope. Oesophageal, LOS, and
      CD pressures; CD electromyogram; and oesophageal pH 5 cm above the LOS were
      recorded in nine healthy subjects. Stimulation of the laryngopharynx induced LOS
      relaxation in the absence of swallow and oesophageal peristalsis. The stimulation
      of epiglottis and arytenoid produced higher incidence of LOS relaxation compared
      to the base of tongue. The magnitude of LOS relaxation differed significantly
      between the three anatomical sites, with greater relaxation occurring at the
      epiglottis and arytenoid compared with the base of the tongue. None of the LOS
      relaxations induced by laryngeal stimulation resulted in inhibition of the CD or
      gastroesophageal reflux. We conclude that stimulation of the laryngopharyngeal
      mechanoreceptors induces LOS but not CD relaxation. The LOS relaxation induced by
      laryngopharyngeal stimulation is not accompanied by acid reflux in fasting state.

PMID- 10886678
TI  - Rectal visceral sensitivity in healthy volunteers: influences of gender, age and
      methods.
AB  - The barostat is a device that maintains a constant pressure within an air-filled
      polyethylene bag by means of a feedback mechanism. The system measures variations
      in rectal tone by recording changes in the intrarectal pressure and volume.
      Different procedures, such as ramp distension or intermittent distension, are
      used to test visceral sensitivity and rectal wall compliance. It is not quite
      clear which method is preferable and how the barostat measurements compare with
      those of the conventional latex balloon. In 28 healthy volunteers (11 males, mean
      age 36, range 22-67 years) rectal distension was performed in two ways: 1
      Pressure-controlled distension, by both intermittent and ramp methods, with
      measurement on the Visual Analogue Scale (VAS, 0-5) at 8, 12, 16, 20, 24, 28, 32
      and 36 mmHg. Hysteresis (comparing area under the curve during deflation and
      inflation with ramp pressure distension) and compliance were calculated. 2 Volume
      controlled distension, with registration of first sensation, urge to defecate and
      maximal tolerated distension. This procedure was compared to conventional water
      filled latex balloon distension. No differences were found between intermittent
      and ramp distension comparing VAS scores at the same pressures. Gender or age did
      not affect the VAS score. Males had larger volumes at the same pressures than
      females. Females had larger hysteresis than males. Older females had larger
      hysteresis than younger females. The pressure volume curves were S-shaped.
      Compliance at maximal tolerated distension (V/p) and maximal dynamic compliance
      (Delta V/Delta p) was higher in males than females. The polyethylene bag had
      higher MTV and MTP compared to the latex balloon. In conclusion, no differences
      were found in volumes, compliance or VAS between the intermittent and the ramp
      pressure-controlled inflation, indicating potential for simplification of the
      procedure. Males had larger rectal volumes and compliances; females had more
      pronounced hysteresis. A systemic difference was found between distension with
      the water-filled latex balloon and with the air-filled polyethylene bag. This
      should be taken into account when interpreting results.

PMID- 10886679
TI  - Prion protein genes and prion diseases: studies in transgenic mice.
AB  - In the past decade, manipulation of PrP genes by transgenesis in mice has
      provided important insights into mechanisms of prion propagation and the
      molecular basis of prion strains and species barriers. Despite these advances,
      our understanding of these unique pathogens is far from complete. This review
      focuses on PrP gene knockout and gene replacement studies, PrP structure and
      function, and transgenic models of human and animal prion diseases. Transgenic
      approaches will doubtless remain the cornerstone of investigations into the prion
      diseases in the coming years, which will include mechanistic studies of prion
      pathogenesis and prion transmission barriers. Transgenic models will also be
      important tools for the evaluation of potential therapeutic agents for prion
      diseases.

PMID- 10886680
TI  - Role of axon-deprived Schwann cells in perineurial regeneration in the rat
      sciatic nerve.
AB  - The role of Schwann cells (SC) in perineurial regeneration after nerve injury has
      not yet been resolved. It was hypothesized that SC alone are able to induce at
      least partial morphological restoration of the destroyed orthotopic perineureum
      (PN). To test the hypothesis, a permanently denervated segment of the rat sciatic
      nerve was made acellular by freeze-thawing, except in its most proximal part
      where non-neuronal cells were left intact. Restoration of the frozen segment by
      these cells was examined by electron microscopy and immunohistochemistry of the
      SC marker, S-100 protein, 4 and 8 weeks after injury. The PN regenerated from
      undifferentiated fibroblast-like cells. In the presence of migrant SC without
      axons, regenerated cells in the place of the former PN were stacked in several
      layers and, in accordance with the hypothesis, partially expressed typical
      features of the perineurial cells (PC): pinocytotic vesicles, short fragments of
      basal lamina and tight junctions. Migrant SC induced formation of pseudo
      minifascicles even in the epineurium. In these, SC organized the adjacent
      fibroblasts into a multilayered circular sheath, and induced their partial
      differentiation towards perineurial cells. Further experiments demonstrated that
      regenerating axons are required for complete morphological differentiation of the
      regenerated perineurial cells either in the orthotopic PN or in minifascicles.

PMID- 10886681
TI  - Temporary middle cerebral artery occlusion in the rat: consistent protocol for a
      model of stroke and reperfusion.
AB  - The intraluminal suture method of middle cerebral artery occlusion (MCAO) in the
      rat (the suture model) is a model of stroke which readily lends itself to
      studying the pathophysiology of post-ischaemic reperfusion. Unfortunately,
      variability of outcome has compromised the potential of the model, but systematic
      studies might characterize a consistent protocol. Therefore, the clinical and
      neuropathological outcome of temporary MCAO and reperfusion in the suture model
      were systematically investigated. Two hours or 4 h of MCAO were employed,
      measuring the extent of infarction at 24 h with triphenyltetrazolium chloride or
      at 72 h with histopathological techniques. Outcome was compared in three rat
      strains. Following 2 h of MCAO, motor function improved during reperfusion in
      Sprague-Dawley, but not in Wistar or Fischer-344 rats. All Sprague-Dawley and
      Wistar rats survived the protocol to 72 h, but 33% of Fischer-344 rats died. The
      extents of infarction and oedema were greater and less variable in Wistar and
      Fischer-344 than Sprague-Dawley rats, and in all three strains, the extent of
      infarction increased with reperfusion time. Following 4 h of MCAO, there was no
      improvement in motor function during reperfusion in Sprague-Dawley rats, and
      mortality was high at 24 h in Wistar (33%) and Fischer-344 rats (83%). Outcome
      was only pursued in Sprague-Dawley rats to 72 h, where the extent of infarction
      was quite variable. It was concluded that the extent and variability of outcome
      following temporary MCAO in the suture model is strain-dependent, and a
      consistent protocol with zero mortality was found in Wistar rats using 2 h of
      MCAO and 70 h of reperfusion.

PMID- 10886682
TI  - Influence of different fixation procedures on the quantification of infarction
      and oedema in a rat model of stroke.
AB  - In pharmacodynamic studies using focal ischaemia models, the size of the infarct
      measured by quantitative histology is the most important outcome measure.
      Precise, unbiased and reproducible assessment of infarct volume is of foremost
      importance. A frequent problem in interventional stroke models is the evaluation
      of infarcts in animals found dead, where instant post-mortem fixation of the
      brain cannot be performed. The purpose of this study was to investigate possible
      bias from perfusion, immediate and 3-h post-mortem delayed immersion fixation on
      the measured volumes of cerebral infarction, oedema and hemispheres in a rat
      embolic stroke model. Thirty-six male Sprague-Dawley rats were thromboembolized
      into the internal carotid artery. After survival for 24 h, the animals were
      divided into three groups: group 1 - immediate perfusion fixation; group 2 -
      immediate immersion fixation of the brain; and group 3 - animals left dead for 3
      h at room temperature before removal of the brain for immersion fixation.
      Following histological preparation and evaluation, the volumes of the hemispheres
      and infarction were measured by quantitative histology and planimetry. Brains
      fixed by immersion were 7% larger than the perfusion-fixed brains. Delaying the
      immersion fixation for 3 h may increase hemisphere volume by a further 12%.
      Independent of the fixation procedure, the size of infarction was approximately
      40% of the ipsilateral hemisphere, and the oedema was approximately 11% of the
      size of the infarct. The used planimetric technique was accurate with measured
      values within +/- 2% of the factual value. In conclusion, sizes of hemispheres,
      infarction and oedema in absolute volume measures are influenced by the effect of
      unwanted variation of brain size caused by biological factors and artificial
      shrinkage caused by fixation, dehydration and heat treatment of the specimens.
      Infarction and oedema expressed relatively in per cent of hemisphere and infarct,
      respectively, are robust measures independent of the investigated fixation
      procedures.

PMID- 10886683
TI  - Microdysgenesis with abnormal cortical myelinated fibres in temporal lobe
      epilepsy: a histopathological study with calbindin D-28-K immunohistochemistry.
AB  - Microdysgenesis is a microscopic cortical malformation reported to occur with
      varying incidence in surgical lobectomies from patients with temporal lobe
      epilepsy (TLE). It may act as a substrate for the seizures. Four patients are
      reported with TLE, hippocampal sclerosis and cortical microdysgenesis which was
      also characterized by the presence of abnormal myelinated fibres running
      tangentially in the superficial cortical laminae and closely associated with
      abnormal clusters of neurones. Similar abnormal cortical fibres have been
      described in other malformations of cortical development including polymicrogyria
      and focal cortical dysplasia and it is therefore likely that these fibres
      represent part of the microdysgenetic malformation not hitherto reported. The
      possibility is discussed that they may also be of functional significance in
      terms of influencing local seizure propagation and the secondary cortical
      neuronal loss observed, predominantly affecting layer II. Studies of calbindin
      interneuronal populations showed preservation of these cells in the
      microdysgenetic cortex, when compared with non-malformed temporal lobes, despite
      an overall reduction in cortical neuronal density. In addition, prominent numbers
      of neurogliaform calbindin-positive nerve cells were observed in the
      microdysgenesis cases and the nature of these cells is speculated upon.

PMID- 10886684
TI  - Changes in expression of NMDA receptor subunits in the rat lumbar spinal cord
      following neonatal nerve injury.
AB  - The vulnerability of motoneurones to glutamate has been implicated in
      neurological disorders such as amyotrophic lateral sclerosis but it is not known
      whether specific receptor subtypes mediate this effect. In order to investigate
      this further, the expression of N-methyl-D-aspartate (NMDA) receptor subunits was
      studied during the first three post-natal weeks when motoneurones are
      differentially vulnerable to injury following neonatal nerve crush compared to
      the adult. Unilateral nerve crush was carried out at day 2 after birth (P2) which
      causes a decrease of 66% in motoneurone number by 14 days (P14). To study
      receptor expression in identified motoneurones, serial section analysis was
      carried out on retrogradely labelled common peroneal (CP) motoneurones by
      combined immunocytochemistry and in situ hybridization (ISH). mRNA levels were
      also quantified in homogenates from lumbar spinal cords in which the side
      ipsilateral to the crush was separated from the contralateral side. The NR1
      subunit of the NMDA receptor was widely distributed in the spinal cord being
      expressed most strongly in motoneurone somata particularly during the neonatal
      period (P3-P7). The NR2 subunits were also expressed at higher levels in the
      somata and dendrites of neonatal motoneurones compared to older animals. NR2B
      mRNA was expressed at low to moderate levels throughout the studied period
      whereas NR2A mRNA levels were low until P21. Following unilateral nerve crush, an
      initial decrease in NR1 mRNA occurred at one day after nerve crush (P3) in
      labelled CP motoneurones ipsilateral to the crush which was followed by a
      significant increase in NR1 subunit expression at 5 days post-injury. This
      increase was bilateral although reaching greater significance ipsilateral to the
      crush compared with sham-operated animals. A significant increase in NR1 and NR2B
      mRNA post injury was also detected in spinal cord homogenates. In addition, the
      changes in levels of NR1 and NR2B mRNA were reflected by comparable bilateral
      changes at P7 in receptor protein determined by quantitative immunocytochemical
      analysis of NR1 and NR2 subunit expression in identified CP motoneurones
      indicating a co-ordinated regulation of receptor subunits in response to injury.

PMID- 10886685
TI  - Prion protein immunoreactivity in brain samples from an unselected autopsy
      population: findings in 200 consecutive cases.
AB  - Immunostaining for prion protein (PrP) using the KG9 monoclonal antibody was
      undertaken on brain sections from an unselected group of 200 post-mortem cases.
      One case of clinically diagnosed vCJD was confirmed and showed widespread
      abundant PrP immunostaining with KG9 and somewhat less abundant PrP with another
      monoclonal antibody, 3F4. PrP immunostaining seen with KG9 was insensitive to
      proteinase K pretreatment in sections from this case of vCJD. Among the remaining
      199 cases, sections from 84 (42%) showed small amounts of PrP immunoreactivity
      with the KG9 antibody, mainly localized to neurones, neural processes and
      argyrophilic plaques of the type seen in ageing and Alzheimer's disease. Purkinje
      cells, swollen (ischaemic) axons, macrophages and microglials cells were also
      occasionally labelled with this antibody in non-CJD cases. Pre-treatment of
      adjacent sections from non-CJD cases with positive KG9 staining abolished this
      staining, indicating that it represented the cellular form of PrP. There were
      differences in age, sex and cause of death in non-CJD cases with some PrP
      immunostaining patterns compared with cases lacking any staining. Specifically, a
      younger mean age, more females and fewer cardiac deaths were found among those
      with neuronal PrP staining patterns. Staining of some features was also
      significantly associated. These findings need to be taken into account when PrP
      immunostaining is used to diagnose prion diseases. They may indicate that
      cellular PrP is increased in the human brain under some circumstances and provide
      insight into the handling of this protein by human brain cells.

PMID- 10886686
TI  - Immunocytochemical characterization of long-term persistent immune activation in
      human brain after herpes simplex encephalitis.
AB  - The clinical, virological and immunocytochemical features of three children who
      recovered from acute herpes simplex encephalitis (HSE) before the age of 2 years,
      and who developed secondary severe focal epilepsy after a symptom-free period,
      leading to neurosurgery 3-10 years later are described. In one child, relapse of
      HSE occurred immediately after surgery. In all three patients, brain sample
      biopsies showed abundant CD3-positive T lymphocytes with a majority of CD8 cells,
      and abundant activated macrophage-microglial cells, a pattern similar to that
      found in acute HSE. Herpes simplex virus DNA was retrieved from the tissue biopsy
      in one case. The long-term persistent cerebral inflammatory process observed
      after HSE differed from that observed in another chronic viral disease, subacute
      sclerosing panencephalitis. This inflammatory reaction may be a result either of
      low-grade viral expression or self-induced immune activation. The role of
      inflammation in triggering epilepsy remains hypothetical. Solving these issues
      should have major therapeutic implications. Herpes simplex virus DNA latency in
      brain may be the source of replicative HSE relapse.

PMID- 10886687
TI  - Astroblastomas revisited. Report of two cases with immunocytochemical and
      electron microscopic study. Histogenetic considerations.

PMID- 10886688
TI  - Intracranial carcinoid without evidence of extracranial disease.

PMID- 10886689
TI  - Anaesthetists and perioperative risk.

PMID- 10886690
TI  - Intraoperative fluid and glucose management in children.

PMID- 10886691
TI  - Preliminary experience with the Doppler ultrasound guided vascular access needle
      in paediatric patients.
AB  - Percutaneous cannulation of the internal jugular vein (IJV) in infants and
      children may be technically difficult and can lead to complications. Various
      techniques exist to achieve successful cannulation and to reduce the rate of
      complications. We report the use of the Doppler ultrasound guided vascular access
      needle (the SMART needle) for IJV cannulation in 10 infants and young children
      (mean age 3.7 months) weighing less than 10 kg (mean weight 5.5 kg) who were to
      undergo cardiac surgery at Great Ormond Street Hospital for Children. Successful
      cannulation was achieved in six out of 10 patients with haematoma complicating
      the procedure in two patients. We believe this is the first reported use of this
      device for cannulation of the IJV in this patient group.

PMID- 10886692
TI  - Applications of intrathecal catheters in children.
AB  - Access to the intrathecal space may be required for sampling of cerebrospinal
      fluid for diagnostic purposes, for the administration of pharmacological agents,
      or for cerebrospinal fluid (CSF) drainage to lower intracranial pressure. The
      current report details five children in whom a percutaneously placed lumbar
      intrathecal catheter was used: (i) to provide intraoperative surgical anaesthesia
      instead of general anaesthesia (ii); to deliver intrathecal fentanyl to provide
      postoperative analgesia (iii); to provide chronic pain control during the
      terminal stages of metastatic malignancy; (iv) to allow repeated doses of
      intrathecal chemotherapy; and (v) to allow CSF drainage and prevent CSF leakage
      following frontal encephalocele repair. The indications and applications of
      intrathecal catheters in the paediatric aged patient are reviewed.

PMID- 10886693
TI  - High frequency oscillatory ventilation during repair of neonatal congenital
      diaphragmatic hernia.
AB  - We evaluated the use of high frequency oscillatory ventilation (HFOV) during
      congenital diaphragmatic hernia repair. After preoperative stabilization, 22
      newborn infants were ventilated with HFOV during surgery. Ventilatory settings,
      blood gas values and oxygenation index were recorded before, during and after
      surgical repair. No differences were noted for these variables. No complications
      related to ventilation were recorded. According to the surgeon, diaphragmatic
      repair during HFOV is facilitated. This study confirms that CDH can be safely
      repaired using HFOV during anaesthesia.

PMID- 10886694
TI  - Local and systemic immune response to surgery under balanced anaesthesia in
      children.
AB  - We studied perioperative changes in the immune response and compared changes in
      the peripheral blood with those in the wound in 20 boys (0.5-3 years) during
      elective inguinal surgery under balanced anaesthesia. Blood samples were drawn
      before premedication, immediately, and 4 or 24 h after anaesthesia. Cells from
      the wound were harvested with the Cellstick device, removed from the wound 4
      (n=10) or 24 h (n=10) after anaesthesia. We found decreased lymphocyte counts in
      the peripheral blood, increased percentages of activated T lymphocytes and B
      lymphocytes, and decreased percentages of total T lymphocytes, T helper cells and
      T cytotoxic cells. The percentages of T helper cells and B lymphocytes were lower
      in the wound than in blood. Mitogen-induced lymphocyte proliferative responses
      decreased. This study demonstrates perioperative changes in the immune response
      in children and, as a new finding, that immune effector cells in the blood and in
      the wound are in a dynamic balance.

PMID- 10886695
TI  - The Newton valve revisited: an in-vitro study of ventilator circuit dead space.
AB  - A laboratory study was conducted to investigate the volume (length) of the
      ventilator circuit dead space (VCD) tubing at which dilution of an inspired gas
      by ventilator driving gas first occurs using three lung models. Various lengths
      of two VCD tubing materials [Portex (Sims Portex Ltd, Kent, UK) 10 mm bore smooth
      walled silicon and Intersurgical (Wokingham, Berks, UK) 22 mm corrugated plastic]
      were interposed between a T-piece circuit and Nuffield 200 ventilator (Penlon,
      Abingdon, Oxon, UK) with a Newton valve attached. Dilution of inspired gas by the
      ventilator driving gas was first detected during ventilation of infant and child
      lung models when the VCD was 7 ml (6 cm) and 77 ml (102 cm), respectively, using
      Portex tubing, and 24 ml (6.5 cm) and 105 ml (29 cm), respectively, using
      Intersurgical tubing. No dilution occurred using the neonatal model. Dilution of
      the inspired anaesthetic gases by ventilator driving gas may occur in paediatric
      practice if the VCD volume (length) is inadequate. This risk is greatest in the
      child.

PMID- 10886696
TI  - Serum glutathione S-transferase alpha as a measure of hepatocellular function
      following prolonged anaesthesia with sevoflurane and halothane in paediatric
      patients.
AB  - We studied the effects of prolonged anaesthesia (4.3-7.7 h) with sevoflurane and
      halothane on hepatic function in 14 paediatric patients. Hepatic function was
      assessed using serum concentrations of liver-specific glutathione S-transferase
      alpha (GSTA) before and 0, 3 and 15 h after the end of anaesthesia. A transient
      significant increase in GSTA over baseline was observed in the sevoflurane group,
      but not in the halothane group, and the difference between the groups was not
      significant. These data suggest that, although statistically insignificant, the
      use of sevoflurane for prolonged anaesthesia in paediatric patients is more
      likely than halothane to be involved in damage to hepatic function.

PMID- 10886697
TI  - Cardiocirculatory changes during videolaparoscopy in children: an
      echocardiographic study.
AB  - We examined cardiovascular changes associated with intra-abdominal insufflation
      in 20 children (mean age 6.1+/-4.7 years, ASA physical status I or II) undergoing
      laparoscopic surgery with general anaesthesia using echocardiography with a
      transthoracic approach. Intra-abdominal pressure never exceeded 10 mmHg. Systolic
      blood pressure, diastolic blood pressure, endtidal CO2, peak, and mean airway
      pressure increased during intra-abdominal insufflation (P < 0.001).
      Pneumoperitoneum was associated with increases (P<0.001) in left ventricular
      enddiastolic volume, left ventricular end-systolic volume and left ventricular
      endsystolic meridional wall stress. In addition, before, during and after intra
      abdominal insufflation, left ventricular fractional shortening and left
      ventricular ejection fraction, underwent slight, insignificant changes.
      Pneumoperitoneum in children has a major impact on cardiac volumes and function,
      mainly through the effect on ventricular load conditions. The sharp increase in
      intra-abdominal pressure affects both preload and afterload, while systolic
      cardiac performance remains unchanged.

PMID- 10886698
TI  - Postbypass pulmonary artery pressure influences respiratory system compliance
      after ventricular septal defect closure.
AB  - It is reported that surgical correction of left-to-right shunt improves
      respiratory function in paediatric cardiac patients. However, such correction
      sometimes does not result in an improvement of respiratory compliance. The
      purpose of this study was to look for factors determining changes in respiratory
      system compliance (Crs) in patients who underwent closure of ventricular septal
      defect (VSD closure). In a prospective study, 17 children (< 10 kg) who underwent
      VSD closure were enrolled. They were divided into two groups, according to
      postbypass mean pulmonary artery pressure (mPAP). The patients were allocated to
      Group C if mPAP was < or = 18 mmHg (n=12) and to Group PH if > 18 mmHg (n=5). We
      compared the ratio of postoperative Crs to preoperative Crs (Cpost/Cpre) between
      the groups. A multiple occlusion technique was used to measure Crs. The
      Cpost/Cpre in group C was larger than that in group PH (1.11+/-0.17 vs. 0.81+/
      0.12, P<0.01). There was a correlation between postbypass mPAP and Cpost/Cpre
      (r(s)=0.49, P<0.05), but no correlation was noted between preoperative mPAP,
      Qp/Qs or Rp/Rs and Cpost/Cpre. We concluded that high postbypass mPAP was
      associated with a perioperative decrease in Crs after VSD closure.

PMID- 10886699
TI  - Recovery after paediatric daycase herniotomy performed under spinal anaesthesia.
AB  - In this prospective survey, recovery in hospital and at home was evaluated in 195
      children aged 6 months to 10 years who had undergone herniotomy under spinal
      anaesthesia as a daycase procedure. Spinal anaesthesia was successful in most of
      the children, with only two patients being given general anaesthesia. Eighty
      three percent of the children had pain at home and 19% had moderate or severe
      pain. Eighty-five percent of the children needed pain medication at home; the
      median dose of analgesics was 4 (1-9, 10th and 90th percentiles). Vomiting was
      noted in two of 195 children in hospital and in 10 of 192 children at home.
      Eleven children developed a mild position-dependent headache. Most of the
      children (183/191) recovered their normal daily activities during the first three
      postoperative days. We conclude that spinal anaesthesia is a safe and effective
      technique for paediatric herniotomy. Moreover, pain is common following
      herniotomy and children should be given analgesics for the first two or three
      postoperative days.

PMID- 10886700
TI  - Emergence agitation in paediatric patients after sevoflurane anaesthesia and no
      surgery: a comparison with halothane.
AB  - This study was designed to compare the emergence characteristics of sevoflurane
      with halothane anaesthesia in paediatric patients having no surgical
      intervention. We randomized 32 ASA I or II paediatric outpatients scheduled for
      magnetic resonance imaging scans to receive either halothane or sevoflurane
      anaesthesia. The primary outcome measure was the percentage of patients with
      emergence agitation, as defined by two different criteria. Time to discharge from
      the postanaesthesia care unit (PACU) and the secondary recovery unit (SRU) were
      compared. Sevoflurane patients had a greater incidence of emergence delirium when
      a high threshold for agitation was defined (33% vs. 0%, P = 0.010) and a lower
      threshold for agitation was applied (80% vs. 12%, P<0.0001). Discharge times from
      the PACU and the SRU were not different. We conclude that there is an increased
      incidence of emergence agitation with sevoflurane anaesthesia compared to
      halothane independent of any painful stimulus.

PMID- 10886701
TI  - Anaesthetic management of liver haemorrhage during laparotomy in a premature
      infant with necrotizing enterocolitis.
AB  - The case of a 680 g premature baby who developed massive spontaneous liver
      haemorrhage during laparotomy for necrotizing enterocolitis is reported. The
      infant survived due to rapid and massive fluid administration, including
      transfusion of large volumes of blood and blood products, in combination with
      high dose inotropic support and the surgical use of packing with thrombostatic
      sponges. Good venous access, including two central venous lines, turned out to be
      very useful.

PMID- 10886703
TI  - Bilateral recurrent laryngeal nerve neuropraxia following laryngeal mask
      insertion: a rare cause of serious upper airway morbidity.
AB  - We report the case of a 4-year-old boy who developed bilateral recurrent
      laryngeal nerve neuropraxia following a routine anaesthetic with a laryngeal mask
      airway. The possible mechanisms of injury and the ways that this rare but
      critical complication might be avoided are discussed.

PMID- 10886702
TI  - Persistent anaphylactic reaction after induction with thiopentone and
      cisatracurium.
AB  - A 6-year-old boy presented for surgery for phimosis. The anaesthetic technique
      included intravenous induction with thiopentone and neuromuscular blockade with
      cisatracurium. Severe persistent bronchospasm and central cyanosis followed the
      administration of these drugs. A continuous i.v. infusion of epinephrine at 0.2
      microg. kg(-1) x min(-1) was necessary to break the severe refractory bronchial
      hyperresponsiveness. There was no previous exposure to anaesthetic drugs and no
      definite family history of allergy. Through increased serum eosinophil cationic
      protein, tryptase and histamine levels and IgE levels specific to cisatracurium,
      we demonstrated an IgE-mediated anaphylactic reaction to cisatracurium in the
      child's first exposure to this new neuromuscular blocking agent. Anaphylactic
      reactions to new anaesthetic drugs may be challenging to recognize and treat
      during general anaesthesia in children. The pathogenesis, diagnosis and
      management of life threatening persistent allergic reactions to intravenous
      anaesthetics are discussed.

PMID- 10886704
TI  - Persistent mydriasis following intravenous atropine in a neonate.
AB  - A neonate whose mother had recently taken amitriptyline developed fixed dilated
      pupils after a modest dose of intravenous atropine. Interaction of atropine with
      neonatal amitriptyline levels is suggested and evidence of neonatal effects from
      maternal antidepressant use is examined. There were no neurological sequelae, and
      the neonate's pupils became reactive again after 7 h.

PMID- 10886705
TI  - Management of tracheal agenesis.
AB  - Complete tracheal agenesis is a very rare congenital anomaly that is only
      compatible with life in some cases with associated tracheo-oesophageal or broncho
      oesophageal fistula. In most cases, concomitant congenital anomalies of the
      heart, digestive tract or genitourinary tract are present. It should be suspected
      in any neonate with a history of hydramnios, absent crying, respiratory distress
      and difficulty in intubation. The possibility for surgical correction or
      palliation rests on the extent of atresia present. We present a case of complete
      tracheal agenesis without tracheo nor broncho-oesophageal fistula (type II by
      Floyd's classification) - the diagnosis of which was prenatally suspected - and
      discuss the important features of the airway management of this condition.

PMID- 10886707
TI  - Annual scientific meeting of the association of paediatric anaesthetists of great
      britain and ireland

PMID- 10886706
TI  - Successful airway control with the laryngeal mask in an infant with Beckwith
      Wiedemann syndrome and hepatoblastoma for central line catheterization.
AB  - We present a case of an infant with severe macroglossia, hypoglycaemia and
      inguinal hernia associated with hepatoblastoma (Beckwith-Wiedemann syndrome) in
      which a laryngeal mask airway (LMA) was useful to secure the airway during
      central line insertion. Carbon dioxide monitoring through LMA proved effective to
      assess airway patency during positioning for central vein puncture. In this
      syndrome, where a potentially difficult airway may be encountered, LMA allowed
      adequate ventilation, avoiding the risk and inconvenience of tracheal intubation.

PMID- 10886708
TI  - Prevention of postoperative vomiting with granisetron in paediatric patients with
      and without a history of motion sickness.

PMID- 10886709
TI  - Author's reply

PMID- 10886710
TI  - Blind intubation via the laryngeal mask: a word of caution.

PMID- 10886711
TI  - A pragmatic approach to fasting in paediatric trauma?

PMID- 10886712
TI  - A novel technique for securing lumbar epidural catheters in children undergoing
      hip surgery.

PMID- 10886714
TI  - Author's reply

PMID- 10886713
TI  - Persistent atrial fibrillation following central venous cannulation.

PMID- 10886715
TI  - More Horner's than meets the eye.

PMID- 10886716
TI  - The immunomodulatory factors of bloodfeeding arthropod saliva.
AB  - There are potent immunomodulators in saliva of the bloodfeeding arthropods which
      transmit many of the world's most serious diseases that may benefit the arthropod
      by preventing the vertebrate host from becoming sensitized to the saliva. In
      addition, saliva can enhance transmission of parasites/pathogens by arthropods.
      As a result, vaccines that target the arthropod (e.g. salivary immunomodulators)
      should be considered as one component of multisubunit vaccines against arthropod
      borne parasites/pathogens. Indeed, since vaccines against the pathogens
      themselves are often not fully protective, vaccines that target several facets of
      the life cycle of the pathogen may be the most effective at controlling disease
      transmission. This review covers known immunomodulatory factors in arthropod
      vector saliva, focusing mainly on sandflies and ixodid ticks.

PMID- 10886717
TI  - Characterization of a differential immunoscreen epitope of Plasmodium falciparum
      using combinatorial agents.
AB  - A differential serological screening of a lambdagt11 cDNA expression library has
      identified several clones, which react exclusively to sera samples from persons
      clinically immune to malaria but not to acute malaria patient sera. One such
      clone, IPf9, has a 315-bp cDNA insert, which was found to be conserved in
      different strains of the human and rodent malarial parasite Plasmodium falciparum
      and Plasmodium berghei, respectively. The induced expression product of IPf9 was
      used to generate polyclonal sera in rabbits. The IPf9 expression product was also
      screened with phage surface display combinatorial libraries to isolate reagents
      that specifically bound to the IPf9 product. The polyclonal antisera and the
      combinatorial reagents recognized a 50-kDa protein from P. falciparum, and a 53
      kDa product from P. berghei. Immunofluorescence studies using asexual and sexual
      stages of P. falciparum showed the protein to be present within the parasite in
      each of the asexual and sexual stages. The combinatorial reagents showed a
      partial inhibition in the growth of P. falciparum in vitro. Mice infected with
      the P. berghei showed the presence of T-cells that exhibited lymphoproliferation
      when stimulated with the IPf9 protein. It is suggested that IPf9 protein is a
      conserved protein epitope, and may be relevant for a protective immune response
      to malaria.

PMID- 10886718
TI  - Dissociation of interleukin-4 and interleukin-5 production following treatment
      for Schistosoma haematobium infection in humans.
AB  - Infection with Schistosoma haematobium, the causative agent of urinary
      schistosomiasis is characterized by high levels of specific immunoglobulin (Ig) E
      and eosinophilia. The primary cytokines driving production of IgE and
      eosinophilia are IL-4 and IL-5, respectively. In this study, IL-4 and IL-5
      production in children from a schistosome endemic area of Zimbabwe were
      investigated. Blood samples were taken, stimulated in vitro with either mitogen
      or schistosome antigens and assayed for IL-4 and IL-5 production. These samples
      produced either IL-4 or IL-5 but rarely both cytokines when blood was cultured in
      vitro for 24 or 48 h. After 72 h culture in vitro, both cytokines were detected
      in most samples. These data imply that while IL-4 and IL-5 are both produced by
      schistosome infected people, they are not necessarily coproduced.

PMID- 10886719
TI  - CD36 folding revealed by conformational epitope expression is essential for
      cytoadherence of Plasmodium falciparum-infected red blood cells.
AB  - CD36 is a membrane glycoprotein and a putative scavenger receptor expressed by
      several cell types. In capillary endothelial cells, it mediates the adherence of
      erythrocytes infected with Plasmodium falciparum. The CD36 sequence contains two
      hydrophobic domains located at the amino-and carboxyl-termini of the protein, but
      the topology of this protein and the functional significance of these domains are
      still not clearly defined. We generated soluble CD36-IgG chimeric molecules by
      fusion of the extracellular domains of CD36 with human immunoglobulin domains.
      The construct containing the N-terminal hydrophobic domain of CD36 was completely
      retained intracellularly as membrane-associated molecule, suggesting that the N
      terminal hydrophobic domain of the CD36 is a real transmembrane domain and that
      CD36 has hairpin topology. A small amount of the CD36-IgG chimeric construct
      lacking both transmembrane domains escaped retention, was correctly processed,
      and accumulated in the extracellular medium as a soluble molecule. This CD36-IgG
      construct failed to bind Plasmodium falciparum-infected erythrocytes. Using
      monoclonal antibodies specific for either conformational or structural epitopes,
      we demonstrate that failure of this CD36-IgG construct to bind infected
      erythrocytes was due to incorrect folding of the soluble chimeric molecule.

PMID- 10886720
TI  - Trypanosoma brucei brucei infection impairs MHC class II antigen presentation
      capacity of macrophages.
AB  - During African trypanosomiasis, macrophages play a central role in T cell
      hyporesponsiveness to parasite-related and unrelated antigens. In this study, the
      ability of macrophages from Trypanosoma b. brucei-infected mice to present
      exogenous antigens to a major histocompatibility complex (MHC) class II
      restricted CD4+ T cell hybridoma was analysed. We demonstrate that the antigen
      presentation capacity of macrophages from infected mice is markedly reduced as a
      result of a lower expression of [MHC class II-peptide] complexes on their plasma
      membrane. This defect did not result from a decreased antigen uptake/catabolism,
      a reduced MHC class II and intercellular adhesion molecule 1 expression on the
      surface of macrophages, a decreased affinity of MHC class II molecules for
      antigenic peptides, a competition between exogenous and parasite antigens, or the
      generation of inhibitory peptides. Our data indicate that the step resulting in
      coexpression of processed antigens and MHC class II molecules is affected in T.
      b. brucei-infected mice. Additionally, macrophages from infected mice secreted IL
      10 that in turn contributes to the impairment of T cell activation.

PMID- 10886721
TI  - Participation of macrophages in glomerular sclerosis through the expression and
      activation of matrix metalloproteinases.
AB  - In order to investigate the role of macrophages in glomeruli in the progression
      of glomerular sclerosis, methyl-cellulose (MC) was administered intraperitoneally
      to Wistar rats, in addition to intravenous injection of anti-thy1-1 antibody. In
      this group of rats (Thy-1 + MC group), many macrophages infiltrated in the lytic
      mesangium accompanied by rupture of capillary loops at an early stage and stayed
      with abundant deposition of mesangial matrices until day 35, whereas the
      proliferative lesions following mesangiolysis almost vanished in the rats treated
      with anti-thy1-1 antibody alone (Thy-1 group). In immunostaining, matrix
      metalloproteinase (MMP)-9 was expressed along regenerating capillaries of the Thy
      1 group and in extracapillary lesions of the Thy-1 + MC group after day 7. In
      gelatin zymography, the gelatinolytic band for MMP-9 was expressed much more
      strongly in the Thy-1 + MC group than in the Thy-1 group at day 3, but it was
      expressed a little more strongly in the Thy-1 group than in the Thy-1 + MC group
      at day 7. The bands for an active form of MMP-2 were more strongly expressed in
      the Thy-1 + MC group than in the Thy-1 group throughout the experimental period.
      These results suggest that persistent accumulation of macrophages in mesangium
      induces glomerular sclerosis through expression and activation of MMP.

PMID- 10886722
TI  - Comparative immunohistochemical analysis of developing kidneys, nephroblastomas
      and related tumors: considerations on their histogenesis.
AB  - Immunoperoxidase analysis was performed to evaluate the phenotypic expression of
      eight renal differentiation antigens in five nephroblastomas, one clear cell
      sarcoma of the kidney (CCSK), one rhabdoid tumor of the kidney (RTK), and four
      related tumors. A total of 19 fetal and pediatric kidneys, including two 6th-week
      mesonephric tissues, were comparatively studied. All the specimens were fixed in
      formalin and embedded in paraffin. Neural cell adhesion molecule (NCAM), a marker
      of the nephrogenic zone of the developing kidney, was consistently expressed in
      the epithelial and blastematous components of nephroblastomas of the common type.
      The epithelial components also commonly expressed NK1 and Leu 7 (CD57), and the
      findings may reflect that both were positive in immature proximal tubules
      directly differentiating from the NCAM-positive immature fetal tubuloglomerular
      buds. In two cases, the epithelial component was immunoreactive for CD10 and WT1
      gene product (WT1-GP). Leu M1, epithelial membrane antigen and CA15-3 were only
      focally expressed in nephroblastomas. Rhabdomyoblasts in the stroma were positive
      for WT1-GP. CCSK was featured by the expression of NCAM and CD10. In RTK, focal
      epithelial differentiation was discerned, with focal positivity of WT1-GP and
      negativity of NCAM. In congenital mesoblastic nephroma, the stromal spindle cells
      were strongly immunoreactive for WT1-GP, while WT1-GP was not expressed in
      solitary multilocular cyst of the kidney. Pancortical nephroblastomatosis was
      featured by the diffuse subcapsular reappearance of immature metanephric tissue.
      Nephroblastomas and related conditions thus offer an adequate model for studying
      human nephrogenesis.

PMID- 10886723
TI  - Expression of vascular endothelial growth factor and its receptors correlates
      closely with formation of the plexiform lesion in human pulmonary hypertension.
AB  - The pulmonary vasculature exhibits various morphological changes in patients with
      pulmonary hypertension (PH). Among them, the plexiform lesion is one of the most
      characteristic vascular lesions, although nothing is known about the molecular
      mechanisms of its formation. In the present study, the expression of vascular
      endothelial growth factor (VEGF), an endothelial cell-specific angiogenic
      mitogen, and its receptors, fms-like tyrosine kinase (Flt-1) and kinase insert
      domain-containing receptor (KDR), in the lungs of five cases with PH, were
      examined. By in situ hybridization, VEGF expression was found in modified smooth
      muscle cells inside the plexiform lesions as well as in medial smooth muscle
      cells of the arteries adjacent to the lesions. The expression of Flt-1 mRNA was
      observed in endothelial cells of the arteries adjacent to the plexiform lesions,
      while KDR mRNA was expressed in the endothelial cells inside the plexiform
      lesions. VEGF was immunolocalized to the endothelial cells expressing its
      receptors as well as the modified smooth muscle cells producing VEGF. These
      results demonstrate that VEGF and its receptors are upregulated with a close
      correlation to the plexiform lesions, and suggest that VEGF expressed by smooth
      muscle cells may activate the endothelial cells to form the plexiform lesions.

PMID- 10886724
TI  - Isoproterenol-induced myocardial injury resulting in altered S100A4 and S100A11
      protein expression in the rat.
AB  - S-100 proteins (S100) are characterized by calcium-binding ability with two
      structural EF hands. Several S100 are expressed in cardiomyocytes and thought to
      play a crucial role in calcium signaling. To examine whether the expression of
      S100 is a response to detectable myocardial damage or regeneration, we
      investigated, immunohistochemically, the expression of S100A4 and S100A11 in the
      isoproterenol (ISP)-treated rat heart. Definite expression of S100A4 and S100A11
      was demonstrated in normal cardiomyocytes, and their staining patterns were
      enhanced in the ISP-treated rat heart, suggesting the possible involvement of S1
      A4 and S100A11 in ISP-induced myocardial damage.

PMID- 10886725
TI  - Microsatellite instability and Epstein-Barr virus infection in gastric remnant
      cancers.
AB  - Clinicopathological analysis, microsatellite analysis, detection of Epstein-Barr
      virus (EBV), and immunohistochemistry on p53 protein were performed in 26 cases
      of gastric remnant cancer (GRC). They were divided into two groups; Group A (n =
      14) who had undergone a primary gastrectomy for benign gastric disease, and Group
      B (n = 12) who had undergone the same operation for gastric cancer. EBV infection
      was present in 29% of Group A, 8% of Group B and 6% of the conventional gastric
      carcinoma (CGC) (Group A vs CGC, P = 0.01). Microsatellite instability (MSI) was
      found in 7% of Group A, 25% of Group B, and 9% of the CGC (Group B vs CGC; P =
      0.08). p53 Overexpression was observed in 46% of the GRC and 33% of the CGC. p53
      Overexpression was observed in 90% of the intestinal type of GRC, but in only 20%
      of the diffuse type of GRC (P = 0.002). The cancer stage was a significant factor
      in the univariate analysis of survival (P = 0.04). In conclusion, GRC is
      different from CGC in terms of MSI or EBV association. The pathogenetic
      differences between the two groups require further investigation. EBV infection
      may have been involved in the carcinogenesis of Group A. MSI may be an important
      factor in the carcinogenesis of metachronous multiple gastric cancer (Group B).

PMID- 10886726
TI  - Endomyometriosis arising in the uterosacral ligament: a case report including a
      literature review and immunohistochemical analysis.
AB  - We report a case of endomyometriosis arising in the left uterosacral ligament of
      a 29-year-old woman. The central cavity of the uterine-like mass was lined by
      pseudo-stratified columnar epithelium and endometrial stroma. The wall of the
      cyst consisted of bundles of smooth muscle cells. Immunohistochemical analysis
      demonstrated both alpha-estrogen receptor and progesterone receptor
      immunoreactivities in the epithelial, stromal and smooth muscle cells. A
      relatively high proliferating activity was also demonstrated in these cells by Ki
      67 immunostaining. These findings suggest that the mass was hormone dependent and
      had a relatively rapid evolution.

PMID- 10886727
TI  - Chondrosarcomatous differentiation in metastatic deposit of serous papillary
      cystadenocarcinoma.
AB  - A rare case of serous papillary cystadenocarcinoma of the ovary showing
      chondrosarcomatous differentiation in a metastatic deposit late in the clinical
      course is reported. A 49-year-old female underwent a total abdominal hysterectomy
      with bilateral salpingo-oophorectomy for bilateral ovarian tumors. Histological
      diagnosis was serous papillary cystadenocarcinoma of both ovaries with lymph node
      metastasis. After six courses of chemotherapy, she was confirmed to be in
      complete remission following a second laparotomy. Following additional
      chemotherapy, a third laparotomy disclosed swollen left inguinal lymph nodes. In
      one of these nodes, approximately 5.0 cm in greatest diameter, the predominant
      histological features were: chondrosarcoma of the bone and soft tissue, with
      small foci of serous papillary adenocarcinoma and squamous epithelium. A
      histological transition between mesenchymal and epithelial areas was identified.
      Immunohistochemical positivity for broad-spectrum cytokeratin (AE1/AE3),
      vimentin, epithelial membrane antigen, and S-100 protein was observed in both
      chondrosarcomatous and epithelial areas. The current evidence may suggest that
      the chondrosarcomatous differentiation was derived from the metastatic epithelial
      component.

PMID- 10886728
TI  - Giant adrenal myelolipoma: case report and review of the literature.
AB  - Myelolipoma is a tumor-like growth composed of mature fat tissue and bone marrow
      elements. It occurs in the adrenal gland or as an isolated soft tissue mass. It
      may be associated with endocrine disorders such as hermaphroditism, Cushing's
      disease, Addison's disease and obesity of unknown cause. These lesions rarely
      measure more than 5 cm in diameter, although giant tumors have been reported in
      the literature. The fifth largest surgically resected adrenal myelolipoma in the
      literature is reported and its clinical associations and, macroscopic and
      microscopic features are discussed.

PMID- 10886729
TI  - Fibromatosis of the mesoappendix.
AB  - Mesenchymal tumors of the appendix are very rare. Mesenteric fibromatosis is the
      most common diagnosis in the case of isolated proliferative fibroblastic lesion
      found in this region. However, the differential diagnosis between fibromatosis
      and well-differentiated fibrosarcoma (Grade I) can be difficult in some
      borderline cases. A rare case of proliferative fibroblastic lesion involving the
      appendix and mesoappendix is presented, and its origin, diagnosis and
      differential diagnosis are discussed.

PMID- 10886730
TI  - Incidentally detected liver metastasis of well-differentiated follicular
      carcinoma of the thyroid, mimicking ectopic thyroid.
AB  - A case of incidentally detected liver metastasis of follicular carcinoma of the
      thyroid, histologically mimicking ectopic thyroid, is described. The patient was
      a 48-year-old woman. A 2-cm mass was incidentally detected in the left lobe of
      the liver by abdominal computed tomography (CT) scan. Partial liver resection was
      performed for diagnosis and treatment. Histologically, the liver nodule was
      composed of small-to-large follicles containing colloid material. The lining
      epithelium was flat or cuboidal and showed no cellular or nuclear atypia.
      Immunohistochemical studies for thyroid-specific proteins, thyroglobulin (Tg),
      triiodothyronine (T3) and thyroxine (T4), suggested that the nodule was of
      thyroid origin. Therefore, a differential diagnosis of metastasis of well
      differentiated thyroid cancer, ectopic thyroid tissue and teratoma was made. The
      patient had a history of subtotal thyroidectomy performed 8 years ago due to a
      thyroid tumor. The original surgical specimens of the thyroid tumor were
      diagnosed as follicular adenoma. Additional sections of the specimen were
      reviewed and an area of convincing vascular invasion was found that was
      suggestive of follicular carcinoma. Subsequent whole-body examination failed to
      find other metastases. It was determined that the liver tumor was metastasized
      from well-differentiated follicular carcinoma of the thyroid.

PMID- 10886731
TI  - Esophageal squamous cell carcinoma characterized by extensive chondroid
      differentiation.
AB  - A rare case of carcinoma characterized by extensive chondroid elements at a site
      of primary esophageal and metastatic lesion is reported. The patient was a 67
      year-old man complaining of dysphagia due to an ulcerative lesion at the lower
      middle esophagus. He underwent irradiation treatment prior to surgery.
      Histologically, the tumor consisted of both carcinomatous and chondroid elements
      and had invaded deeply into the esophageal wall. The carcinomatous cells had
      gradually become chondroid cells embedded within an extensive extracellular
      matrix. In addition, the metastatic lesion showed findings similar to those of
      the primary lesion. Immunohistochemistry revealed that both carcinomatous and
      chondroid elements were immunostained with cytokeratin and epithelial membrane
      antigen, suggesting an epithelial nature to the chondroid cells. Conversely, only
      chondroid cells were positively stained for S-100 protein. Furthermore, bone
      morphogenetic proteins (BMP) were positive for chondroid cells and their
      surrounding carcinomatous cells. Given the apparent transition between
      carcinomatous and chondroid cells based on microscopy and immunohistochemical
      findings in the present case, we concluded that the chondroid cells were derived
      from carcinomatous cells. In addition, our findings suggest that BMP produced by
      carcinomatous cells lead to chondroid differentiation of the carcinoma cells.

PMID- 10886732
TI  - Ovarian yolk sac tumor with virilization during pregnancy: immunohistochemical
      demonstration of Leydig cells as functioning stroma.
AB  - A case is reported of yolk sac tumor occurring in the left ovary and complicated
      by pregnancy. The 22-year-old patient presented at 28 weeks gestation with
      virilization and elevated serum levels of testosterone and alpha-fetoprotein. The
      tumor showed the typical features of yolk sac tumor with a mixture of islands of
      Leydig cells. The accumulations of Leydig cells were well demarcated from the
      cellular components of the yolk sac tumor and were distributed throughout the
      tumor, although with predominant localization at the periphery. By
      immunohistochemistry the Leydig cells were intensely positive for vimentin and
      negative for cytokeratins, allowing clear distinction from the cell components of
      the yolk sac tumor, which were positive for cytokeratins and negative for
      vimentin. Testosterone was also identified in the cytoplasm of the Leydig cells.
      After tumor resection the testosterone and alpha-fetoprotein levels declined
      simultaneously; this, together with the immunohistochemical demonstration of
      testosterone, indicates that the Leydig cells were responsible for the endocrine
      manifestations. Furthermore, antibodies against inhibin alpha-subunit and
      calretinin could be used to detect the Leydig cells. The present case, a
      combination of yolk sac tumor and Leydig cells acting as a functioning stroma and
      causing virilization during pregnancy, is very rare.

PMID- 10886733
TI  - Cyclin D1 expression in ductal carcinoma in situ, atypical ductal hyperplasia and
      usual ductal hyperplasia: an immunohistochemical study.
AB  - The cell cycle regulatory gene, Cyclin D1, plays a critical role in the growth
      and progression of several types of human cancer, including breast cancer.
      Immunohistochemical study of Cyclin D1 expression has been extensively reported
      in invasive ductal carcinoma (IDC). In contrast, there have been few reports
      concerning Cyclin D1 expression in ductal carcinoma in situ (DCIS) and their
      positive rates are variable. The differences in the reported frequency may be
      largely due to the differences in antibodies used, immunohistochemical methods
      and the positive cut-off point. However, we speculated that the strictness of
      diagnosis of DCIS might be somewhat responsible for these differences in
      frequency. Therefore, we selected cases of DCIS by carefully eliminating cases of
      predominantly intraductal carcinoma (PIC). Moreover, to clarify whether Cyclin D1
      expression is involved in multistep carcinogenesis or the progression of human
      breast cancer, we immunohistochemically investigated Cyclin D1 expression in 57
      DCIS, 10 atypical ductal hyperplasia (ADH), 70 usual ductal hyperplasia (UDH), 44
      PIC and 92 IDC. Cyclin D1 expression was detected in 41 DCIS cases (72%), 22 PIC
      cases (50%) and 40 IDC cases (43%). No expression of Cyclin D1 was observed in
      either ADH or UDH. There were no significant correlations between Cyclin D1
      expression and histological grade or estrogen receptor expression in DCIS. These
      results suggest that Cyclin D1 expression may play an important role in the early
      stages of carcinogenesis, and that immunohistochemical detection of Cyclin D1
      expression may be helpful in differentiating low-grade DCIS from ADH.

PMID- 10886734
TI  - Expression of osteopontin messenger RNA by macrophages in ovarian serous
      papillary cystadenocarcinoma: a possible association with calcification of
      psammoma bodies.
AB  - Calcified psammoma bodies often appear in human ovarian serous papillary
      cystadenocarcinoma. Osteocalcin (OC), osteonectin (ON) and osteopontin (OPN) are
      three members of non-collagenous bone-related proteins known to be related with
      mineralization of bone. To clarify possible involvement of these bone matrix
      proteins in the calcification of the psammoma bodies, the expression of OC, ON
      and OPN was analyzed by immunohistochemical and in situ hybridization studies
      using 15 surgical specimens. OPN protein was detected in the calcified area of
      the psammoma bodies which was positively stained by von Kossa's staining, while
      OC and ON proteins were not. OPN protein was not detected in any cells in
      tissues, but OPN messenger ribonucleic acid (mRNA) was detected in CD68-positive
      macrophages, indicating that OPN was produced and promptly secreted by
      macrophages. These results suggest that OPN produced and promptly secreted by
      macrophages and subsequently translocated to psammoma bodies may be causally
      related with the calcium phosphate deposition in the psammoma bodies of the
      ovarian serous papillary cystadenocarcinomas.

PMID- 10886735
TI  - Immunohistochemical adrenomedullin expression is decreased in the placenta from
      pregnancies with pre-eclampsia.
AB  - The purpose of the present study was to investigate whether placental
      immunohistochemical adrenomedullin expression in normal normotensive pregnancies
      is different from that in pregnancies with pre-eclampsia. Placental tissues were
      obtained from seven normal normotensive pregnancies and 12 pregnancies with pre
      eclampsia. The intensity of adrenomedullin staining in syncytiotrophoblasts was
      evaluated by means of immunohistochemistry and the ratio of the number of intact
      tertiary villi to that of total tertiary villi (intact/total villi ratio) was
      determined. The intensity of adrenomedullin expression in the placenta obtained
      from pregnancies with pre-eclampsia was significantly decreased compared with
      expression in placentas from uncomplicated normotensive pregnancies (P < 0.005).
      The intact/total villi ratio in placentas obtained from pregnancies with pre
      eclampsia was significantly lower than that in placentas from normal normotensive
      pregnancies (P < 0.0001). In the amnion and extravillous trophoblast cells in
      both groups, no difference for the intensity of adrenomedullin expression was
      noted. These results suggest that adrenomedullin synthesis in the villous
      syncytiotrophoblasts is decreased in pregnancies with pre-eclampsia.

PMID- 10886736
TI  - Mucinous endometrial adenocarcinoma simulating microglandular hyperplasia of the
      cervix.
AB  - A case of endometrial adenocarcinoma simulating microglandular hyperplasia (MGH)
      of the cervix is presented. A postmenopausal 53-year-old woman, with no previous
      history of taking exogenous hormones, presented with vaginal bleeding. An
      endometrial biopsy exhibited a tumor composed predominantly of a microglandular
      proliferation of tightly packed glands with mild to moderate atypia and mitotic
      figures. The majority of the tumor cells contained intracytoplasmic mucin. There
      were numerous neutrophils within the microglandular lumens and in the stroma. The
      tumor was focally positive for carcinoembryonic antigen and vimentin. The MGH
      like proliferation, focally, had a transition to a conventional mucinous
      adenocarcinoma. Hysterectomy specimens showed a residual mucinous endometrial
      adenocarcinoma with no myometrial invasion, the uterine cervix was unremarkable.
      Four years following her hysterectomy the patient was well, with no evidence of
      disease. Pathologists need to be cautious about MGH-like changes in the
      endometrial biopsy of postmenopausal women and be aware of this type of
      endometrial cancer as it may be misdiagnosed.

PMID- 10886737
TI  - Mature teratoma of the uterine corpus with thyroid differentiation.
AB  - A case of a clinically silent mature teratoma of the uterine corpus is reported.
      A 55-year-old woman presented with multiple uterine leiomyomas. The discovery was
      incidental, because the patient was asymptomatic. Macroscopically, a colloid
      hemorrhagic-looking nodule was present. Histologic and immunohistochemical
      studies showed that this tumor was a small thyroid mass. Key words:,

PMID- 10886738
TI  - An autopsy case of ovarian hyperstimulation syndrome with massive pulmonary edema
      and pleural effusion.
AB  - Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of
      ovulation induction with exogenous gonadotropins, such as human menopausal
      gonadotropin and follicle-stimulating hormone. These hormones are considered to
      increase capillary permeability and cause third space fluid shift. We report an
      autopsy case of severe OHSS in a 28-year-old Japanese female. The patient
      developed bilateral chest pain and progressive dyspnea during the course of
      administration of human gonadotropins. Pleural effusion and hypouresis clinically
      disappeared 4 days after the onset of the symptoms, but the patient died suddenly
      of rapid respiratory insufficiency. Autopsy examination revealed massive
      pulmonary edema, intra-alveolar hemorrhage and pleural effusion without any
      evidence of pulmonary thromboembolism. Histopathological examination of the ovary
      demonstrated multiple well-developed follicle formations, consistent with OHSS.
      It is very important to recognize that massive pulmonary edema can occur in a
      patient with OHSS. To the best of our knowledge, this is the first autopsy report
      of a patient with severe OHSS.

PMID- 10886739
TI  - Anaplastic osteosarcoma with abundant eosinophilic cytoplasm and minimal osteoid
      production.
AB  - A case of osteosarcoma with unusual microscopic features, occurring in the right
      proximal tibial metaphysis of a 12-year-old boy is reported. Radiographically,
      the tumor was ill-defined and purely osteolytic. On gross examination, the tumor
      was soft, fragile, spongy and red to brown in color. Microscopically, the tumor
      consisted of pleomorphic cells possessing abundant eosinophilic cytoplasm,
      including cells larger than 100 microm in diameter. The cells were arranged in a
      sheet, with few extracellular collagen fibers. Multiple sectioning of the
      specimens revealed a small amount of osteoid production. Immunohistochemical
      study revealed a positive reaction for vimentin and osteocalcin. Electron
      microscopic study suggested the fibroblastic or osteoblastic origin of the cells.

PMID- 10886740
TI  - Dedifferentiated liposarcoma with chondroblastic osteosarcomatous
      dedifferentiation.
AB  - We describe a rare case of dedifferentiated liposarcoma with features resembling
      chondroblastic osteosarcoma in the dedifferentiated component. The tumor was
      removed from the left thigh in a 78-year-old male. It consisted of a well
      differentiated liposarcoma and an anaplastic component that contained numerous
      osteoid and cartilaginous tissues surrounded by high-grade spindle cell sarcoma.
      To our knowledge, only two cases similar to the divergent chondroblastic
      osteosarcomatous dedifferentiation of this disease have been reported in the
      literature.

PMID- 10886741
TI  - Sarcomatoid carcinoma of the renal pelvis: a case report.
AB  - A case of sarcomatoid carcinoma of the renal pelvis is reported. A 72-year-old
      male was admitted with a chief complaint of right flank pain. Clinical imaging
      studies revealed marked dilation of the right renal pelvis caused by a tumor at
      the pyeloureteric region. Right nephrectomy was performed in June 1999. The 8.4 x
      6.5 cm tumor was grossly polypoid in appearance and protruded into the renal
      pelvis. Histologically, sarcomatoid spindle cells predominated over the
      carcinomatous component (mainly transitional cell carcinoma, partly associated
      with squamous cell and adenocarcinoma components). Osteoclast-like CD68-positive
      multinucleated giant cells were scattered. The sarcomatoid component was
      immunoreactive for both cytokeratin and vimentin. Sarcomatoid cells negative for
      cytokeratin were also noted. In both the sarcomatoid and carcinomatous
      components, nuclear overexpression of p53 oncoprotein was confirmed. The
      histogenesis of sarcomatoid carcinoma of the renal pelvis is discussed.

PMID- 10886742
TI  - A case of atypical granular cell tumor of the neurohypophysis.
AB  - A case of granular cell tumor (GCT) arising in the neurohypophysis of a 63-year
      old woman is reported. The tumor consisted of ovoid, polygonal or spindle-shaped
      cells in a sheet-like or fascicular arrangement. Its abundant cytoplasm contained
      granules positive for diastase-resistant periodic acid-Schiff reaction.
      Ultrastructurally, the tumor cells contained numerous polymorphic lysosomes of
      various densities. Immunohistochemically, the tumor cells were positive for S-100
      protein, glial fibrillary acidic protein and Leu7, suggesting that the tumor
      originated from pituicytes that were thought to be modified astrocytes in the
      neurohypophysis and its stalk. The granular cells showed nuclear atypia,
      pleomorphism and increased mitotic activity. Therefore, the present tumor was
      considered as a histologically atypical GCT. Interestingly, proliferating cell
      nuclear antigen, Ki-67 and p53 were stained in a few tumor cells of this case.
      These findings indicate that the present tumor had a malignant potential.

PMID- 10886743
TI  - Malignant intramuscular forearm tumor with overwhelming squamous element.
AB  - Squamous cell carcinoma (SCC) arising in the skeletal muscle is rare. A case of a
      19-year-old female patient with an intramuscular forearm tumor showing a
      histopathologically overwhelming squamous element is presented. Microscopic
      examination revealed the classical features of SCC, including horn pearls,
      individual cell keratinization and intercellular bridge. A malignant spindle cell
      component was not detected. Neither evidence of another primary site nor skin
      lesion over the tumor was found and no metastatic lesion was detected in the 5
      years since the appearance of the mass.

PMID- 10886744
TI  - Epithelioid sarcoma of the penis: a case report and review of the literature.
AB  - A rare case of epithelioid sarcoma (ES) of the penis is presented. The patient, a
      35-year-old man, was initially treated as having Peyronie's disease, but the
      subsequent appearance of a subcutaneous nodule displayed a 'distal-type' ES. At
      immunohistochemical phenotypification, the tumor was positive for vimentin,
      cytokeratins and epithelial membrane antigen (EMA), as well as for some other
      multidirectional antibodies, including a membranous reaction for CD99. The review
      of 11 similar cases so far reported in the literature led to the conclusion that
      the clinicopathological characteristics of penile ES are basically the same as
      those of tumors in more classical locations: the age at diagnosis ranged from 23
      to 43 years, the interval between first manifestations and diagnosis averaged 37
      months (delayed diagnosis being common because of the slow growth rate and the
      harmless appearance of the lesion), the typical sign was a superficial nodule or
      mass, usually accompanied (better preceded) by urethral stenosis, dysuria and
      erectile disturbances. Total or partial penectomy was the treatment of choice in
      most patients, but lack of adequate follow up did not permit any definitive
      conclusion to be reached regarding its efficacy.

PMID- 10886745
TI  - Asymmetric periflexural exanthem of childhood: microbiologic case-control study.
AB  - Our objective was to study possible etiologic factors of asymmetric periflexural
      exanthem of childhood (APEC) among a large panel of microbiologic agents not yet
      investigated. To do so, we designed a prospective case-control study using
      throat, stool, blood, and skin samples, and enlisted 37 children with APEC and 37
      age-matched controls without eruption seen consecutively from February 1995 to
      April 1996 from a mixed referral center and community-based population. No
      interventions were done. Used as the main outcome measure was the differences in
      the two groups for microbiologic investigations. No significant statistical
      differences between cases and controls for virus and bacteria investigated were
      found. No microorganism was identified as a possible etiologic agent in any of
      the APEC patients. APEC is not a nonspecific cutaneous eruptive pattern to
      several common microbiologic agents. More sophisticated molecular approaches are
      needed to address its etiology.

PMID- 10886746
TI  - A comparative study of pediatric onset psoriasis with adult onset psoriasis.
AB  - Psoriasis in childhood is not uncommon. We report data collected from 223
      pediatric onset and 484 adult onset psoriasis patients. In the pediatric onset
      psoriasis patients (POPPs), prevalence of family history was 68.2% compared to
      54% in the adult onset psoriasis patients (AOPPs). Also we noticed that
      exacerbation of psoriasis induced by precipitating factors such as stress (50.4%
      in POPPs, 42. 7% in AOPPs), pharyngitis (27.9% in POPPs, 12.2% in AOPPs), and
      trauma (49.6% in POPPs and 38.9% in AOPPs) were more frequent in POPPs. Our data
      show that the frequency of spontaneous remission in POPPs was 35.3% compared to
      24.3% in AOPPs. A disfiguring skin disease in childhood may have profound
      emotional effects. Childhood psoriasis needs special attention. To achieve a
      prolonged remission it is essential that children with psoriasis and their
      parents have an understanding of the exogenous and endogenous factors responsible
      for the increased morbidity of psoriasis.

PMID- 10886747
TI  - Bart syndrome: the congenital localized absence of skin may follow the lines of
      Blaschko. Report of six cases.
AB  - Three cutaneous manifestations are characteristic of Bart syndrome: congenital
      localized absence of skin (CLAS), mucocutaneous blistering, and nail
      abnormalities. Six cases of Bart syndrome are herein reported. Localized absence
      of skin is present at birth, particularly on the anterior aspects of the lower
      extremities and dorsa of the feet. Physical trauma in utero has been proposed as
      a mechanism to explain the denuded areas on the limbs. The recurrent, highly
      similar pattern of the congenital defect in regard to location and clinical
      appearance in our patients and in most of the reported cases strongly suggests
      that trauma is too simplistic an explanation. Because of the observed bilateral
      and symmetric distribution of denuded areas in an S-shaped broad band, their
      sharply demarcated borders, the involvement of the toe webs, and the frequent
      similar involvement of the soles, we suggest that congenital localized absence of
      skin in Bart syndrome may follow the lines of Blaschko.

PMID- 10886748
TI  - Nodular tuberculid: a report of four patients.
AB  - The tuberculids are hypersensitivity reactions to Mycobacterium tuberculosis
      (MTB) and include papulonecrotic tuberculid (PNT), lichen scrofulosorum, erythema
      induratum of Bazin (EIB), and phlebitic tuberculid. Papulonecrotic tuberculid
      displays papulonecrotic lesions mostly on the extensor surfaces of the limbs.
      Histopathology shows necrosis, granulomatous inflammation (GI), and occasionally
      vasculitis, usually in the superficial dermis. Erythema induratum of Bazin shows
      nodulo-ulcerative lesions on the posterior aspect of the legs. Histopathology
      reveals a septolobular panniculitis, necrosis, GI, and vasculitis. The Mantoux
      test is strongly positive and associated tuberculosis (TB) may be present in both
      conditions. MTB cannot be demonstrated with a Ziehl-Neelsen (ZN) stain or
      cultured. The polymerase chain reaction has demonstrated MTB DNA in PNT (50%) and
      EIB (25%). The tuberculids respond to full anti-TB treatment. We document four
      patients with nodules on the legs in whom the pathologic changes were situated in
      the deep dermis and adjacent subcutaneous fat. Nodular tuberculid (NT) is
      regarded as a suitable term for these lesions. All patients were female. Their
      ages were 19 months, 12 years, 17 years, and 5 years. All patients presented with
      nodules on the limbs. These nodules were approximately 1 cm in diameter, dull red
      or bluish-red, and nontender. Ulceration was not present. The number of nodules
      varied from a few to many. The Mantoux test was strongly positive in all the
      patients. Associated pulmonary TB was present in two patients. Histopathology
      showed GI (n = 4), vasculitis (n = 2), and coagulative necrosis (n = 2). A ZN
      stain was negative in each case. All patients received anti-TB treatment for 6
      months [rifampicin (n = 4), isoniazid (n = 4), pyrazinamide (n = 4), and
      ethambutol (n = 2)]. At 12 months follow-up, skin and pulmonary lesions had
      resolved in all. Nodular tuberculid should be distinguished from arthropod bites
      and papular urticaria, dermal erythema multiforme, evolving vasculitis, evolving
      folliculitis, and erythema nodosum. Histopathologically NT should be
      distinguished from other causes of granulomatous vasculitis and GI with or
      without necrosis. In children with nodules on the limbs unresponsive to routine
      treatment, skin biopsy should be done to exclude NT. Nodular tuberculid
      represents a hybrid between PNT and EIB with characteristic clinicopathologic
      features and should be included in the classification of cutaneous TB.

PMID- 10886749
TI  - Characteristics of vitiligo in Korean children.
AB  - Eighty Korean children (ages 8 months-12 years) with clinical and/or
      histopathologic diagnoses of vitiligo were evaluated; 39 boys and 41 girls. The
      mean age at first visit was 7.9 years and the mean age at onset was 5.6 years.
      The most common site of onset was the head/neck area (58.8%), followed by the
      trunk and lower limbs. The children were compared with a control group of 422
      adults with vitiligo. Children comprised 16% of the total vitiligo patients and
      adults comprised 84%. A family history of vitiligo was found in 11 (13.8%)
      children, compared to 10.7% in the adult group; poliosis in 20 (25. 0%); halo
      nevi in 2 (2.5%), compared to 4.0% in the adult group; combined autoimmune and
      endocrine diseases in 1 (1.3%), compared to 7.6% in the adult group; and
      segmental vitiligo in 26 (32.5%), compared to 13.0% in the adult group. The
      combined diseases were significantly less often found in children than adults (p
      < 0.01), and segmental vitiligo was significantly more often associated with
      children (p < 0.0001). Our study did not show a higher prevalence of vitiligo in
      girls as reported in other studies, which may indicate racial differences. Of the
      total 502 patients, only 1 patient with segmental vitiligo had halo nevi. Sixty
      four percent of the children with vitiligo responded to treatment, compared to
      57% of the adults.

PMID- 10886750
TI  - Telangiectasia macularis eruptiva perstans.
AB  - Telangiectasia macularis eruptiva perstans (TMEP) is a form of mastocytosis. It
      is an uncommon condition, particularly in children. The disorder is characterized
      by telangiectatic macules and generally has a good prognosis, with little
      tendency to urticate or cause constitutional symptoms. We report a girl who
      presented at age 2 with a 6-month history of erythematous macules on her arms and
      legs. The lesions were larger and possessed a more angular configuration than
      classic telangiectases. They slowly spread to her torso and face; there were no
      associated constitutional symptoms. Histopathologic examination showed dilated
      capillaries and increased numbers of mast cells, consistent with TMEP.
      Mastocytosis should be considered in patients presenting with telangiectatic
      lesions that are atypical in appearance, distribution, or onset.

PMID- 10886751
TI  - Diffuse cutaneous mastocytosis with bone marrow infiltration in a child: a case
      report.
AB  - Mastocytosis encompasses a range of disorders characterized by overproliferation
      and accumulation of tissue mast cells. Mast cell disease is most commonly seen in
      the skin, but the skeleton, gastrointestinal tract, bone marrow, and central
      nervous system may also be involved. We present a 10-year-old boy with diffuse
      cutaneous mastocytosis characterized by disseminated papular, nodular, and
      infiltrated leathery lesions. The patient presented with chronic diarrhea and
      malnutrition. Laboratory studies were normal except for an elevated urinary 1
      methylhistamine level. The bone marrow aspirate showed a dense mast cell
      infiltrate confirming systemic involvement.

PMID- 10886752
TI  - An unusual form of Stevens-Johnson syndrome with subcorneal pustules associated
      with Mycoplasma pneumoniae infection.
AB  - We report a 10-year-old girl in whom Stevens-Johnson syndrome (SJS) (with acute
      gingivostomatitis and conjunctivitis) was associated with a pustular eruption
      clinically and histologically similar to Sneddon-Wilkinson subcorneal pustulosis.
      This is a very rare form of SJS, the true incidence of which is probably
      underestimated.

PMID- 10886753
TI  - A cutaneous eruption from G-CSF in a healthy donor.
AB  - A healthy 12-month-old donor treated with G-CSF for collection of stem cells from
      peripheral blood developed a discrete, papular, erythematous eruption which
      histologically showed irregularly shaped lymphocytes with mitoses. We suggest
      that such a reaction is due to activation of lymphocytes by G-CSF in a normal
      host, leading to atypical changes in cellularity.

PMID- 10886754
TI  - Disseminated BCG infection following bone marrow transplantation for X-linked
      severe combined immunodeficiency.
AB  - An 8-month-old boy with X-linked severe combined immunodeficiency (XSCID)
      developed disseminated bacille Calmette-Guerin (BCG) infection following BCG
      vaccination at birth. He initially presented with an abscess at the site of BCG
      vaccination and was begun on three-drug antituberculous treatment (rifampicin,
      isoniazid, and pyrazinimide). Dissemination was subclinical prior to a human
      leukocyte antigen (HLA)-identical bone marrow transplant (BMT) from his sister,
      following which he presented with an acute erythroderma. A skin biopsy specimen
      revealed granulomas with epithelial histiocytes and giant cells in the reticular
      dermis, and numerous acid-fast bacilli (AFB) were present on Ziehl-Nielsen stain.
      A diagnosis of disseminated BCG disease was made. Despite the addition of a
      fourth antituberculous agent, ethambutol, he did not recover and developed
      numerous skin abscesses over the following weeks. Examination of pus from these
      lesions demonstrated numerous AFB. Clarithromycin was added as a fifth
      antituberculous agent. Despite five-drug antituberculous therapy and monthly
      intravenous immunoglobulin infusions, recurrent abscesses containing AFB
      developed intermittently until 7 months posttransplant. At follow-up 1 year post
      BMT he showed good general physical improvement. All abscesses had healed with
      scarring, and no further skin lesions had occurred.

PMID- 10886755
TI  - Verrucous hemangioma: report of two cases and review of the literature.
AB  - Verrucous hemangiomas are usually congenital lesions which typically present as
      warty, bluish, vascular papules, plaques, or nodules, mainly on the lower limbs
      of children. They show no tendency to spontaneous resolution, and tend to spread
      and recur after inadequate treatments. We report two instances of verrucous
      hemangioma, one in an adult and one in a child, discuss the clinical,
      histopathologic, and therapeutic aspects of this entity, and review the
      literature.

PMID- 10886756
TI  - AEC syndrome and CHAND syndrome: further evidence of clinical overlapping in the
      ectodermal dysplasias.
AB  - Among the ectodermal dysplasias, there are several examples of overlapping
      phenotypes in disorders that are considered distinct. We report a 5-year-old boy
      born to nonconsanguineous parents and presenting with ectodermal dysplasia,
      ankyloblepharon filiforme adnatum, and bilateral choanal atresia consistent with
      the diagnosis of AEC syndrome. We compare the findings in our patient with the
      previous reported cases and discuss the overlapping phenotype of this disorder
      with CHAND syndrome.

PMID- 10886757
TI  - Bilateral en coup de sabre-a rare entity.
AB  - Linear scleroderma involving the frontal or frontoparietal region of the scalp
      (with or without associated facial hemiatrophy) is called "en coup de sabre"
      (like the stroke of a sabre). We report a case which to the best of our knowledge
      is only the fifth instance of this subset of localized morphea occurring in a
      bilateral distribution. We believe that the rarity of this presentation warrants
      a report.

PMID- 10886758
TI  - Gianotti-Crosti syndrome in an infant following immunization.
AB  - Gianotti-Crosti syndrome (GCS) is a distinctive, self-limiting acropapular or
      papulovesicular eruption. Typical clinical presentation is that of a monomorphic,
      nonpruritic eruption most commonly involving the face, neck, buttocks, and
      extremities. It tends to occur in childhood, though infrequently it has been
      reported in adults. We report GCS occurring in an infant following immunization.

PMID- 10886759
TI  - Transient beneficial effect of GH replacement therapy and topical GH application
      on skin ulcers in a boy with prolidase deficiency.
AB  - A diagnostic examination for short stature in a boy with chronic ulcers of the
      feet due to prolidase deficiency, a rare disorder associated with intractable
      ulcers of the skin, led to the diagnosis of growth hormone (GH) deficiency.
      Replacement treatment with r-hGH associated with the topical application of a GH
      containing ointment when the boy was 13 years old resulted in complete but
      transitory healing of the ulcers, which can probably be attributed to the growth
      promoting effects of GH on dermal connective tissue.

PMID- 10886760
TI  - What syndrome is this? Cardio-facio-cutaneous (CFC) syndrome.

PMID- 10886761
TI  - Tender blue mass in an 8 year old.

PMID- 10886762
TI  - Raney clips: excision of vascular lesions on the scalp made (ridiculously)
      simple.

PMID- 10886763
TI  - Cutis marmorata telangiectatica congenita: early detection in two premature
      infants.

PMID- 10886764
TI  - Discoid lupus erythematosus in childhood.

PMID- 10886765
TI  - Infantile psoriasis: successful treatment with topical calcipotriol.

PMID- 10886766
TI  - KID syndrome: report of a case and support for its reclassification as an
      ectodermal dysplasia.

PMID- 10886767
TI  - Complex structure of a maize Myb gene promoter: functional analysis in transgenic
      plants.
AB  - The maize P gene encodes a Myb-like transcription factor that regulates synthesis
      of red flavonoid pigments in floral organs. To study the transcriptional
      regulation of the P gene, candidate regulatory sequences of the P1-rr gene
      promoter were identified by Ac insertional mutagenesis and subjected to
      functional testing in transgenic maize plants. The results indicate that a 561 bp
      fragment (Pb) encompassing the transcription start site (-235 to +326) supports
      weak expression of a GUS reporter gene in floral organs, including husk, silk,
      kernel pericarp, cob and male inflorescence. Two other fragments, located
      approximately 1 and 5 kb 5' of the transcription start site, increased the levels
      of GUS activity in floral tissues and thus appear to contain enhancer elements.
      All of the tested constructs gave similar patterns of GUS expression, suggesting
      that the 561 bp Pb fragment that is common among the transgene constructs
      contains regulatory elements that promote activation in floral organs. The basal
      promoter and proximal enhancer fragments contain putative binding sites for bZip
      regulatory factors, and a complex arrangement of palindromes including a large
      inverted repeat of two tRNA-like genes. Possibly, interconversions between linear
      and cruciform conformations of the palindromes may affect protein/DNA
      interactions and thereby modulate P1-rr expression.

PMID- 10886768
TI  - Arabidopsis seed coat development: morphological differentiation of the outer
      integument.
AB  - A morphological description of the differentiation of the outer integument of the
      Arabidopsis thaliana seed is presented. The period covered starts at about the
      octant embryo stage, extends to the mature seed, and concludes beyond that at the
      initial stages of seed imbibition. During this period the two-cell-layered outer
      integument goes through a dramatic differentiation process. The outer cell layer
      secretes mucilage in a ring between the plasma membrane and the outer cell wall
      at the corners of the cell. This secretion forces the cytoplasm into a columnar
      shape in the center of the cell. Before and during this process, starch granules
      are produced, initially at the center of the outer wall and later within the
      column. Late in differentiation, the starch granules are degraded as the cell
      produces a highly reinforced wall surrounding the columnar protoplast and at the
      radial walls between adjacent cells. This results in a cell containing large
      amounts of mucilage surrounding and completely outside of a highly reinforced
      columella. The mucilage and outer wall then dehydrate to leave the columella and
      radial walls visible as the epidermal plateau and reticulations visible on the
      mature seed. The inner cell layer of the outer integument also produces and
      degrades starch granules concomitantly with the outer layer but produces no
      mucilage. In the mature dry seed the collapsed outer wall remains connected to
      the top of the columella and the radial walls, but these connections are rapidly
      broken as the mucilage fully hydrates.

PMID- 10886769
TI  - A xylem-specific cellulose synthase gene from aspen (Populus tremuloides) is
      responsive to mechanical stress.
AB  - Angiosperm trees accumulate an elevated amount of highly crystalline cellulose
      with a concomitant decrease in lignin in the cell walls of tension-stressed
      tissues. To investigate the molecular basis of this tree stress response, we
      cloned a full-length cellulose synthase (PtCesA) cDNA from developing xylem of
      aspen (Populus tremuloides). About 90% sequence similarity was found between the
      predicted PtCesA and cotton GhCesA proteins. Northern blot and in situ
      hybridization analyses of PtCesA gene transcripts in various aspen tissues, and
      PtCesA gene promoter-beta-glucuronidase (GUS) fusion analysis in transgenic
      tobacco, demonstrated conclusively that PtCesA expression is confined to
      developing xylem cells during normal plant growth. During mechanical stress
      induced by stem bending, GUS expression remained in xylem and was induced in
      developing phloem fibers undergoing tension stress, but was turned off in tissues
      undergoing compression on the opposite side of the bend. Our results suggest a
      unique role for PtCesA in cellulose biosynthesis in both tension-stressed and
      normal tissues in aspen, and that the on/off control of PtCesA expression may be
      a part of a signaling mechanism triggering a stress-related compensatory
      deposition of cellulose and lignin that is crucial to growth and development in
      trees.

PMID- 10886770
TI  - Carotenoid biosynthesis during tomato fruit development: regulatory role of 1
      deoxy-D-xylulose 5-phosphate synthase.
AB  - Plant isoprenoids represent a heterogeneous group of compounds which play
      essential roles not only in growth and development, but also in the interaction
      of plants with their environment. Higher plants contain two pathways for the
      biosynthesis of isoprenoids: the mevalonate pathway, located in the
      cytosol/endoplasmic reticulum, and the recently discovered mevalonate-independent
      pathway (Rohmer pathway), located in the plastids. In order to evaluate the
      function of the Rohmer pathway in the regulation of the synthesis of plastidial
      isoprenoids, we have isolated a tomato cDNA encoding 1-deoxy-D-xylulose 5
      phosphate synthase (DXS), the first enzyme of the pathway. We demonstrate in vivo
      activity and plastid targeting of plant DXS. Expression analysis of the tomato
      DXS gene indicates developmental and organ-specific regulation of mRNA
      accumulation and a strong correlation with carotenoid synthesis during fruit
      development. 1-Deoxy-D-xylulose feeding experiments, together with expression
      analysis of DXS and PSY1 (encoding the fruit-specific isoform of phytoene
      synthase) in wild-type and yellow flesh mutant fruits, indicate that DXS
      catalyses the first potentially regulatory step in carotenoid biosynthesis during
      early fruit ripening. Our results change the current view that PSY1 is the only
      regulatory enzyme in tomato fruit carotenogenesis, and point towards a
      coordinated role of both DXS and PSY1 in the control of fruit carotenoid
      synthesis.

PMID- 10886771
TI  - Tissue-specific induction of the mRNA for an extracellular invertase isoenzyme of
      tomato by brassinosteroids suggests a role for steroid hormones in assimilate
      partitioning.
AB  - Brassinosteroids (BRs) induce various growth responses when applied exogenously
      to plant tissues, and the analysis of biosynthetic mutants reveals an essential
      role for plant growth and development. Only a few BR-regulated genes have been
      identified so far, and the corresponding gene products are assumed to be involved
      in cell elongation. The present study shows that BR growth responses are linked
      to the regulation of carbohydrate metabolism by induction of the mRNA for the key
      enzyme of an apoplastic phloem-unloading pathway. Addition of BRs to autotrophic
      tomato suspension culture cells specifically elevates the activity of cell-wall
      bound invertase, whereas the intracellular invertase activities were not
      affected. This enhanced enzyme activity was shown to correlate with the induction
      of the mRNA of extracellular invertase Lin6, whereas the mRNA levels of the other
      three extracellular invertase isoenzymes were not affected. The induction level
      induced by different BRs correlates with their growth-promoting activity. The
      physiological significance of this regulation is further supported by the low
      concentrations and short incubation times required to induce Lin6 mRNA. This
      regulatory mechanism results in an elevated uptake of sucrose via the hexose
      monomers, and thus an increased supply of carbohydrates to the BR-treated cells.
      Experiments with tomato seedlings showed that the localized BR-dependent growth
      response of the hypocotyl elongation zone was accompanied by a specific induction
      of Lin6 mRNA that is restricted to the corresponding tissues. This study
      demonstrates a role of BRs in tissue-specific source/sink regulation.

PMID- 10886772
TI  - Downy mildew (Peronospora parasitica) resistance genes in Arabidopsis vary in
      functional requirements for NDR1, EDS1, NPR1 and salicylic acid accumulation.
AB  - To better understand the genetic requirements for R gene-dependent defense
      activation in Arabidopsis, we tested the effect of several defense response
      mutants on resistance specified by eight RPP genes (for resistance to Peronospora
      parasitica) expressed in the Col-0 background. In most cases, resistance was not
      suppressed by a mutation in the SAR regulatory gene NPR1 or by expression of the
      NahG transgene. Thus, salicylic acid accumulation and NPR1 function are not
      necessary for resistance mediated by these RPP genes. In addition, resistance
      conferred by two of these genes, RPP7 and RPP8, was not significantly suppressed
      by mutations in either EDS1 or NDR1. RPP7 resistance was also not compromised by
      mutations in EIN2, JAR1 or COI1 which affect ethylene or jasmonic acid signaling.
      Double mutants were therefore tested. RPP7 and RPP8 were weakly suppressed in an
      eds1-2/ndr1-1 background, suggesting that these RPP genes operate additively
      through EDS1, NDR1 and as-yet-undefined signaling components. RPP7 was not
      compromised in coi1/npr1 or coi1/NahG backgrounds. These observations suggest
      that RPP7 initiates resistance through a novel signaling pathway that functions
      independently of salicylic acid accumulation or jasmonic acid response
      components.

PMID- 10886773
TI  - Transformation of Medicago truncatula via infiltration of seedlings or flowering
      plants with Agrobacterium.
AB  - Two rapid and simple in planta transformation methods have been developed for the
      model legume Medicago truncatula. The first approach is based on a method
      developed for transformation of Arabidopsis thaliana and involves infiltration of
      flowering plants with a suspension of Agrobacterium. The second method involves
      infiltration of young seedlings with Agrobacterium. In both cases a proportion of
      the progeny of the infiltrated plants is transformed. The transformation
      frequency ranges from 4.7 to 76% for the flower infiltration method, and from 2.9
      to 27.6% for the seedling infiltration method. Both procedures resulted in a
      mixture of independent transformants and sibling transformants. The transformants
      were genetically stable, and analysis of the T2 generation indicates that the
      transgenes are inherited in a Mendelian fashion. These transformation systems
      will increase the utility of M. truncatula as a model system and enable large
      scale insertional mutagenesis. T-DNA tagging and the many adaptations of this
      approach provide a wide range of opportunities for the analysis of the unique
      aspects of legumes.

PMID- 10886774
TI  - In vivo analysis of plant promoters and transcription factors by agroinfiltration
      of tobacco leaves.
AB  - A convenient, Agrobacterium-mediated transient expression assay has been
      evaluated for rapid analysis of plant promoters and transcription factors in
      vivo. By simple infiltration of Agrobacterium cells carrying appropriate plasmid
      constructs into tobacco leaves in planta, reproducible expression assays could be
      conducted in as little as 2-3 days without using expensive equipment (e.g.
      biolistic gun or electroporation apparatus) or complicated procedures (e.g.
      preparation of protoplasts). Biotic and abiotic treatments could be applied to
      the intact plant to examine their influence on promoter activity and gene
      expression. Using this method, we have tested the stress-responsive as-1 and heat
      shock elements, yeast GAL4 transactivation system, two promoters of pathogenesis
      related (PR) genes as well as a heat shock promoter. Through deletion analyses of
      tobacco PR1a promoter and a novel myb1 promoter, we have also successfully
      identified the cis-regulatory regions in these promoters that are responsive to
      salicylic acid treatment or tobacco mosaic virus infection. Together, our results
      demonstrate that Agrobacterium-mediated transient expression is a simple and
      efficient method for in vivo assays of plant promoters and transcription factors.

PMID- 10886775
TI  - Intron-tagged epitope: a tool for facile detection and purification of proteins
      expressed in Agrobacterium-transformed plant cells.
AB  - Epitope tagging provides a useful tool for immunological detection and cellular
      localization of proteins in vivo. Using T-DNA-mediated transformation, the
      detection of epitope-tagged proteins in planta is currently feasible only in
      transgenic plants, because an artificial expression of cDNA and gene constructs
      driven by plant promoters in bacteria obscures an early detection of epitope
      tagged proteins in Agrobacterium-infected plant cells. We have developed a method
      for labelling plant coding sequences with intron-tagged epitope-coding domains
      that are not processed in Agrobacterium. Here we show that the expression of HA
      epitope-tagged constructs encoding beta-glucuronidase and S-phase kinase
      associated (AtSKP1/ASK1) proteins can be specifically and exclusively detected in
      cultured Arabidopsis cells as early as five days after Agrobacterium infection.
      This epitope-tagging approach offers an unlimited source of transformed material
      for purification and localization of proteins expressed individually or
      simultaneously in Agrobacterium-transformed plant cells.

PMID- 10886776
TI  - T-DNA insertional mutagenesis for functional genomics in rice.
AB  - We have produced 22 090 primary transgenic rice plants that carry a T-DNA
      insertion, which has resulted in 18 358 fertile lines. Genomic DNA gel-blot and
      PCR analyses have shown that approximately 65% of the population contains more
      than one copy of the inserted T-DNA. Hygromycin resistance tests revealed that
      transgenic plants contain an average of 1.4 loci of T-DNA inserts. Therefore, it
      can be estimated that approximately 25 700 taggings have been generated. The
      binary vector used in the insertion contained the promoterless beta-glucuronidase
      (GUS) reporter gene with an intron and multiple splicing donors and acceptors
      immediately next to the right border. Therefore, this gene trap vector is able to
      detect a gene fusion between GUS and an endogenous gene, which is tagged by T
      DNA. Histochemical GUS assays were carried out in the leaves and roots from 5353
      lines, mature flowers from 7026 lines, and developing seeds from 1948 lines. The
      data revealed that 1.6-2.1% of tested organs were GUS-positive in the tested
      organs, and that their GUS expression patterns were organ- or tissue-specific or
      ubiquitous in all parts of the plant. The large population of T-DNA-tagged lines
      will be useful for identifying insertional mutants in various genes and for
      discovering new genes in rice.

PMID- 10886777
TI  - Intestinal intraepithelial lymphocytes contain a CD3- CD7+ subset expressing
      natural killer markers and a singular pattern of adhesion molecules.
AB  - Intestinal intraepithelial lymphocytes (i-IEL) represent one of the largest, non
      organized lymphoid population in the body. They are located outside the
      epithelial basement membrane among the mucosal epithelial cells. We, and
      previously other groups, have reported the presence of a CD7+CD3-IEL subset in
      the epithelium of human small intestine. This subset is drastically reduced in
      coeliac disease (CD) patients. In the present work we accomplish a better
      phenotypic characterization of this CD3-IEL subset and demonstrate the expression
      of typical natural killer (NK) cell markers. Most, if not all, CD3-CD7+ cells
      express NKPR1 (CD161)[98% +/- 2] and CD122[92% +/- 6]. In addition, a variable
      percentage express CD2[55% +/- 16], CD94[24% +/- 18], CD56[44% +/- 21] and
      CD16[12% +/- 4], however, no CD57 expression was observed. Moreover, these cells
      contain perforin granules[75% +/- 5], supporting a potential cytolytic ability.
      Regarding adhesion molecules, CD18 and CD44 expression is absent, which is
      consistent with a limited capacity of migration. Altogether, these data suggest
      the presence of intraepithelial NK cells in human intestinal epithelium, a
      compartment where cytotoxic effectors have not been clearly defined.

PMID- 10886778
TI  - Serum amyloid A secretion from monocytic leukaemia cell line THP-1 and cultured
      human peripheral monocytes.
AB  - Serum amyloid A (SAA), an acute-phase protein and a precursor of fibrous
      components in reactive amyloid deposits, is synthesized mainly in the liver under
      the stimulation of inflammation-related cytokines. In addition, the SAA gene is
      expressed in monocytes/macrophages, which are believed to play a central role in
      amyloid fibrillogenesis. Consequently, the pathogenic implication of SAA produced
      from these cells has been of major concern. Because SAA synthesis at the protein
      level in such cells has never been analyzed quantitatively, in this study an
      enzyme-linked immunosorbent assay was generated with a detection level
      sufficiently high to measure SAA concentrations in the culture supernatants of
      the human monocytic leukaemia cell line THP-1. SAA secretion by THP-1 with
      interleukin (IL)-1beta required the presence of dexamethasone as proposed
      previously. We also found that unidentified components in fetal calf serum (FCS)
      could induce SAA production by THP-1 in the presence of dexamethasone. These
      findings are in contrast to the results obtained from hepatoma cell line HepG2,
      in which IL-1beta alone could induce SAA secretion, while dexamethasone
      supplemented FCS could not. The method was able to quantify SAA secreted from
      cultured human peripheral monocytes. The findings suggest that monocytes produce
      SAA in almost the same manner as THP-1. Thus, THP-1 cells can be utilized to
      investigate a distinctive manner of SAA production from monocytes.

PMID- 10886779
TI  - Interleukin-10 produced by the innate immune system masks in vitro evidence of
      acquired T-cell immunity to E. coli.
AB  - Bacteria trigger stimulation of antigen-specific, as well as innate, immune
      responses. Cytokines and other products of cells belonging to the innate immune
      system may interfere with the detection of acquired immunity to whole bacteria in
      vitro. Proliferation and cytokine production by human blood mononuclear cells in
      response to a whole UV-killed Escherichia coli was compared with the response to
      commonly used antigen preparations: purified protein derivative (PPD), Candida
      albicans and influenza proteins. E. coli induced a weaker proliferative response
      with later onset than did the other antigens, and production of interferon (IFN)
      gamma comparable with that in response to C. albicans and influenza vaccine, but
      lower than that induced by PPD. Both proliferation and IFN-gamma production were
      abolished by removal of CD4 cells or blocking of HLA-D, but not CD1 antigen
      presenting molecules. Purified lipopolysaccharide (LPS) induced neither
      proliferation nor IFN-gamma production. None of the antigen preparations
      stimulated interleukin (IL)-4 production but, in contrast to the other antigens,
      whole E. coli, as well as purified O6 LPS, induced large quantities of IL-10. IL
      10 production was independent of CD4 cells or HLA-D molecules. Blocking of IL-10
      by neutralizing antibodies increased both E. coli-induced proliferation and IFN
      gamma production markedly. Conversely, the addition of whole E. coli or LPS to
      cultures stimulated with other antigens (C. albicans or Staphylococcus aureus)
      down-regulated proliferative and IFN-gamma responses, an effect which was at
      least partly IL-10 dependent. The results indicate a substantial T-cell memory to
      commensal E. coli, but suggest that the evidence of such memory, e.g.
      proliferation and IFN-gamma production, is effectively prevented by IL-10 and
      perhaps other factors produced by monocytes in response to bacteria. Thus, the
      innate immune responses must be taken into account when acquired immune responses
      to microbes are measured.

PMID- 10886780
TI  - Non-major histocompatibility complex dependent variations in lymphocyte activity
      between inbred mouse strains susceptible to various autoimmune diseases.
AB  - Transgenic techniques in inbred mouse strains are powerful tools to investigate
      the specific roles of genes in biological pathways and disease models. However,
      there is increasing concern over the influence of a variable genetic background
      in such experiments. To date there have been few investigations of the
      immunological differences between inbred mouse strains used in models of
      autoimmune diseases. Here we phenotyped lymph node cells and T-cell cytokine
      production in B10.Q (H2q), B10.RIII (H2r), C3H.Q (H2q), C3H. NB (H2p), NOD
      (H2g7), RIII/SJ (H2r) and DBA/1J (H2q) mice. We found several significant
      differences. The C3H strains and RIII/SJ lymph node cells had a high ratio of T
      cells/B cells (> 2 : 1) and a high ratio of CD4/CD8 positive cells (> 3 : 1),
      these strains are therefore denoted high T cell ratio (HiTR) strains. B10 strains
      and DBA/1, however, displayed an expansion of gammadeltaT cells after mitogen
      activation. T cells derived from C3H and DBA/1J strains produced more interleukin
      (IL)-4 than did T cells from B10 and NOD strains. DBA/1J and B10.Q showed a 10
      fold increase in interferon (IFN)-gamma producing cells in the CD4+ T-cell
      population. Variation in the number of IL-2 and IFN-gamma producing T cells
      between the B10 major histocompatibility complex (MHC) congenic strains was the
      only difference possibly controlled by the MHC region. We conclude that non-MHC
      genes influence the numbers of T cells and B cells in lymph nodes, as well as IFN
      gamma, IL-4 and IL-10 production by T cells.

PMID- 10886781
TI  - Reduced formation of phosphatidic acid upon B-cell receptor triggering of mouse B
      lymphocytes lacking Bruton's tyrosine kinase.
AB  - Btk deficient (BtkM) mouse B-lymphocytes do not proliferate when stimulated with
      anti-immunoglobulin (anti-Ig) antibodies. In order to characterize the molecular
      basis of this unresponsiveness we have compared early signal transduction
      pathways triggered by ligating the B cell antigen receptor (BCR) of purified
      resting B cells from normal C57BL/6 (wild-type) and BtkM mice on C57BL/6
      background. BCR-induced signalling events that occur during the first few minutes
      of activation, such as bulk tyrosine phosphorylations, mitogen-activated protein
      kinase (MAPK) activation, PI3-kinase dependent PKB/Akt kinase
      phosphorylation/activation and PLCgamma2 tyrosine phosphorylation are comparable
      in wild type and BtkM B cells. However, the initial extracellular calcium influx
      is reduced and the BCR-induced accumulation of phosphatidic acid (PA) display a
      more transient profile in the BtkM cells. BCR ligation did not induce detectable
      phosphatidyl-choline PLD activity, suggesting that the reduced PA is owing to a
      reduction in the phospho-inositide hydrolysis. These findings further support the
      notion that the proliferative defect of Btk deficient mouse B cells in response
      to anti-immunoglobulin stimulation stems from a failure to sustain phospholipase
      dependent signalling.

PMID- 10886782
TI  - Activation of murine peritoneal macrophages by Streptococcus pneumoniae type II
      capsular polysaccharide: involvement of CD14-dependent pathway.
AB  - In this study we examined the ability of capsular polysaccharide type 2 (PS) from
      Streptococcus pnemoniae to induce secretory and cellular responses in peritoneal
      macrophages. Tumour cytotoxicity induced by preincubation with PS was
      demonstrated to be concentration-dependent. PS-induced tumouricidal activity was
      partially abrogated by anti-tumour necrosis factor (TNF)-alpha and inhibitor of
      nitric oxide, whereas anti-interferon (IFN)-alpha/beta antibody and the
      scavengers of reactive oxygen intermediates had no effect. In addition,
      supernatants from macrophages treated with PS contained TNF-alpha, and their iNOS
      enzymatic activity was significantly increased. Thus, the tumouricidal activity
      induced by PS appeared to be mediated by the production of TNF-alpha and nitrite.
      Treatment of macrophages with PS increased the expression of CD14, the receptor
      for lipolysaccharide (LPS)/LPS-binding protein. Moreover, blocking antibody to
      CD14 abrogated partially TNF-alpha and nitrite induction by PS, suggesting that
      the PS-induced CD14 upregulation was correlated with secretion of TNF-alpha and
      nitrite. Taken together, these results demonstrate that PS may induce macrophage
      secretory and cellular activities, in part, possibly via CD14-dependent pathway.

PMID- 10886783
TI  - Mucin inhibition of lymphocyte function does not require specific mucin-ligand
      interactions.
AB  - Mucins are large highly glycosylated molecules that have been postulated to
      interfere with certain cell-cell interactions. Steric, charge and specific
      signalling effects have been postulated for the inhibition by cell-surface mucin
      molecules. In this report we evaluate the inhibitory effects of bovine
      submaxillary mucin (BSM), a mucin without specific lymphocyte interactions, on
      lymphocyte function. BSM inhibits the adhesion of lymphocytes when coimmobilized
      with intercellular adhesion molecule-1 (ICAM-1) and blocks the activation of T
      lymphocytes when coimmobilized with anti-CD3. These data demonstrate a general
      mucin effect on lymphocyte adhesion and activation that is primarily steric in
      nature and implicates mucins as general barriers to lymphocyte-tumour cell
      interactions. Mucin blockade of cell-cell interactions may explain why mucinous
      tumours are often associated with a poor prognosis.

PMID- 10886784
TI  - CD135 (Flk2/Flt3) expression by human thymocytes delineates a possible role of
      FLT3-ligand in T-cell precursor proliferation and differentiation.
AB  - The expression of the Flk2/Flt3 molecule (CD135), the receptor for Flt3 ligand
      (FL), was investigated in the human thymus. Results showed that there is a high
      level of expression of CD135 by thymocyte populations, especially by intrathymic
      T-cell precursor populations. As these results suggested a role for FL in the
      regulation of thymic T-cell precursor differentiation and/or proliferation, we
      used an in vitro model of thymic stromal cell cultures in order to delineate the
      activity of FL on human CD7(high)CD3-CD4-CD8- triple negative intrathymic T-cell
      precursors. Results showed that FL, either alone or in combination with stem cell
      factor (SCF) induced the proliferation of CD7(high) precursors, but to a lower
      extent than interleukin-7 (IL-7) or IL-7 + SCF, used as positive controls. In the
      presence of FL + SCF, CD7(high) cells developed mainly towards a CD11b+ phenotype
      whereas IL-7 + SCF preferentially induce a CD3+TcRgammadelta+CD8+ phenotype.
      Taken together, these data suggest that FL may play a role in inducing the
      proliferation of CD7(high) human intrathymic T-cell precursors, but also in the
      induction of a myeloid differentiation pathway within the human thymus.

PMID- 10886785
TI  - Nitric oxide promotes growth and major histocompatibility complex-unrestricted
      cytotoxicity of interleukin-2-activated rat lymphocytes.
AB  - The effect of nitric oxide (NO) on growth and major histocompatibility
      complex(MHC)-unrestricted cytotoxicity of interleukin(IL)-2-cultivated rat spleen
      nonadherent mononuclear cells was examined. NO donor sodium nitroprusside (SNP)
      at relatively low concentrations increased magnitude, as well as duration of IL-2
      induced proliferative response of nonadherent splenocytes. SNP effect depended
      completely on released NO, because it was prevented by NO scavenger haemoglobin,
      but not mimicked by expired SNP solution, unable to generate NO, or ferricyanide,
      a second breakdown product of SNP. Other NO donors - SIN-1, SNAP and GSNO failed
      to exert SNP-like growth-enhancing action, probably as a consequence of rapid NO
      generation, compared to sustained NO release by SNP. All NO-releasing chemicals
      at high concentration blocked IL-2-induced proliferation. Growth-promoting effect
      of SNP-derived NO was independent of guanilat cyclase activation, because
      dibutyryl cGMP did not affect IL-2-triggered splenocyte proliferation. Macrophage
      NO acted in a manner similar to SNP; at low concentrations it promoted IL-2
      induced splenocyte growth, however higher amounts were suppressive. Cytotoxicity
      of IL-2-activated splenocytes against NK-sensitive K562 cell line was
      significantly increased when SNP was present during cultivation with IL-2.
      Proportion of NKR-P1+ and CD25+ cells, as well as per cell expression of these
      important activation molecules were increased upon SNP treatment, suggesting
      possible mechanism for the observed NO action.

PMID- 10886786
TI  - Differences in the ligand specificity between CD1d-restricted T cells with
      limited and diverse T-cell receptor repertoire.
AB  - The natural killer (NK) T-lymphocyte population consists of two subsets utilizing
      a diverse and restricted T-cell receptor (TCR) repertoire, respectively. Both
      populations have been shown to include autoreactive cells. NKT cells carrying
      restricted Valpha14(AV14S1)Jalpha281/Vbeta8.2(BV8S2A1 ) TCR have been shown to
      recognize alpha-galactosylceramide (alphaGalCer) presented in the context of
      murine CD1d. In this study we screened a set of murine CD1d-autoreactive T-cell
      hybridomas with diverse TCR for their reactivity with several glycosylated
      variants of ceramide, including alphaGalCer. These hybridomas showed a different
      pattern of reactivity to CD1d-expressing antigen-presenting cells (APC) and were
      not reactive with any of the tested variants of ceramide. A second set of
      hybridomas had been selected for expression of Valpha14 and Vbeta8.2 TCR chains.
      These cells responded to alphaGalCer presented on CD1d, but were only weakly
      reactive to syngeneic splenocytes or CD1d-transfected cells. Their fine
      specificity in the response to glycosylation variants of ceramide demonstrated a
      homogenous reactivity pattern, including reactivity to alpha
      galactosylsphingosine, the variant of alphaGalCer with truncated fatty acyl
      chain. These findings underline the differences in ligand specificity between the
      two subsets of CD1d-restricted NKT cells, and demonstrate a similarity in
      reactivity among the hybridomas using the Valpha14-Jalpha281/Vbeta8.2 TCR.

PMID- 10886787
TI  - Immune activation in the intestinal mucosa before the onset of colitis in
      Galphai2-deficient mice.
AB  - G-protein subunit Galphai2-deficient mice spontaneously develop an inflammatory
      bowel disease that clinically and histopathologically resembles ulcerative
      colitis in humans. The aim of this study was to determine whether immunological
      changes precede the development of colitis in Galphai2-deficient mice. Therefore,
      Galphai2-deficient mice with no clinical or histopathological signs of colitis
      were compared with Galphai2-deficient mice with established colitis and wild-type
      animals, concerning immunological parameters. Healthy Galphai2-deficient mice
      displayed an increased frequency of CD4+ T cells and a decreased frequency of
      CD19+ B lymphocytes in the intestinal mucosa compared with control mice. The CD4+
      population was characterized by a memory phenotype, i.e. increased expression of
      CD44 and decreased expression of CD45RB and CD62L, as well as increased
      expression of the mucosal homing receptors integrins alpha4beta7 and alphaEbeta7.
      Production of pro-inflammatory cytokines, interleukin (IL)-1beta and interferon
      (IFN)-gamma, were increased in Galphai2-deficient mice before clinical signs of
      disease were evident. In addition, total immunoglobulin (Ig)G and IgA levels in
      large intestinal secretions were increased significantly compared with wild-type
      mice, and antibodies specific for the normal intestinal flora in large intestinal
      secretions were present in Galphai2-deficient mice several weeks before the onset
      of colitis. In contrast, antibodies against tropomyosin, a putative autoantigen
      in human ulcerative colitis, were not found in Galphai2-deficient mice before the
      onset of colitis, although they were present in animals with established disease.
      In conclusion, activation of the intestinal immune system precedes
      histopathological and clinical signs of inflammation in Galphai2-deficient mice,
      suggesting that immune abnormalities play an important role in the induction of
      colitis.

PMID- 10886788
TI  - Interleukin-12 in human boutonneuse fever caused by Rickettsia conorii.
AB  - Interleukin (IL)-12 contributes to the resistance against a number of
      intracellular pathogens. We examined the potential biological role of IL-12 by
      studying peripheral blood mononuclear cells (PBMC), its production and its effect
      on cytokine synthesis in 20 Sicilian patients with boutonneuse fever (BF) caused
      by Rickettsia conorii. Data indicate that PBMC from acute BF patients were able
      to produce IL-12 in response to in vitro stimulation with rickettsial antigen
      (Ag): this production was higher than that detected in healed patients. Monocytes
      were the main source of IL-12 by PBMC from BF patients. IL-12 secretion by in
      vitro Ag-stimulated PBMC from BF patients was potentiated by recombinant
      interferon gamma (IFN-gamma) or anti-IL-10 monoclonal antibodies (MoAbs).
      Furthermore, the treatment with anti-IL-12 MoAbs reduced the IFN-gamma synthesis.
      These results indicate that treatment of PBMC from acute BF patients with IL-12
      shifted the response toward a Th1-type cytokine response. Furthermore, IL-12 and
      IFN-gamma are interdependent and they may be associated with the immunity against
      rickettsias.

PMID- 10886789
TI  - Change of Th0 to Th1 cell-cytokine profile following tuberculosis chemotherapy.
AB  - T cells mediate protection against tuberculosis, but little is known about their
      role during chemotherapy of patients with active disease. Here we examined the
      cytokine profile of CD4 T cells before and after four months of chemotherapy in
      six initial skin test anergic cases. Purified protein derivative (PPD) and 16-kDa
      antigen-reactive CD4 T-cell clones prior to therapy resided mostly in disease
      associated body fluids and were of the Th0 (interferon (IFN)-gamma + interleukin
      (IL)-4) secreting profile. In contrast, the majority of postchemotherapy CD4 T
      cell clones originated from blood and were of the IFN-gamma secreting Th1 type.
      However, the recognition of several peptides derived from the 16-kDa antigen was
      not significantly different between the Th1 and Th0 clones. We conclude that
      chemotherapy shifts CD4 T cells from the affected body fluids to the blood
      circulation, accompanied by a change from Th0 to Th1 cytokine profile.

PMID- 10886791
TI  - Drugs for 'neglected diseases': a bitter pill.

PMID- 10886790
TI  - Binding of immune complexes to erythrocyte CR1 (CD35): difference in requirement
      of classical pathway components and indication of alternative pathway-mediated
      binding in C2-deficiency.
AB  - Deficiency of complement components within the classical pathway is associated
      with increased risk for immune complex disease. However, C2-deficient individuals
      often have a mild disease and about 50% are healthy. To study the importance of
      the different components for immune complex clearance, bovine serum albumin
      (BSA)/anti-BSA complexes were opsonized in human serum and the binding to
      erythrocyte complement receptor type 1 (CR1, CD35) was measured in vitro. In C2
      depleted serum the complexes were opsonized and bound to CR1 but the reaction
      needed a longer opsonization time than in normal human serum (NHS). In contrast,
      serum reagent lacking C1q, C4 or C3 did not promote binding in this assay system.
      We also demonstrated that elevated levels of factor B could restore binding of
      complexes to erythrocytes in C2-depleted serum via alternative pathway
      activation. These results indicate that in spite of lack of a complete classical
      pathway, C2-deficient individuals could retain some immune complex opsonizing
      activity via the alternative pathway. This finding could contribute to the
      understanding of differences in association between complement deficiency and
      immune-complex disease.

PMID- 10886792
TI  - A randomized comparison of branded sodium stibogluconate and generic sodium
      stibogluconate for the treatment of visceral leishmaniasis under field conditions
      in Sudan.
AB  - OBJECTIVE: To compare the outcome of treatment of Sudanese kala-azar patients
      treated under field conditions with either branded sodium stibogluconate (SSG)
      (Pentostam GlaxoWellcome) or generic SSG (Albert David Ltd, Calcutta, supplied by
      International Dispensary Association, Amsterdam). METHOD: Randomised comparison.
      271 patients were treated with Pentostam and 245 with generic SSG. RESULTS: No
      statistically significant differences in cure rate or mortality were detected
      between Pentostam and generic SSG. No differences in side-effects between the two
      drugs were noted. The initial cure rate at the time of discharge was 93.7 and
      97.6%, respectively; the death rate during treatment 5.9 and 2.4%. Six months
      follow up was achieved in 88.5% of the discharged patients. Two patients had died
      in the Pentostam group and two had died in the generic SSG group, giving a final
      death rate of 7.5 and 3.7%. The number of relapses in the Pentostam and generic
      SSG groups were 3 and 1, respectively. The final cure rates, calculated at 6
      months after discharge, were 91.3% and 95.9%. CONCLUSION: No difference was
      observed in the performance of generic SSG compared to Pentostam for the
      treatment of visceral leishmaniasis in Sudan. Generic SSG can be routinely and
      safely used for the treatment of kala-azar. Generic SSG costs only 1/14 of the
      price of Pentostam. The use of generic SSG may make treatment of kala-azar
      affordable for national governments in Africa.

PMID- 10886793
TI  - Viewpoint: filovirus haemorrhagic fever outbreaks: much ado about nothing?
AB  - The recent outbreak of Marburg haemorrhagic fever in the Democratic Republic of
      Congo has put the filovirus threat back on the international health agenda. This
      paper gives an overview of Marburg and Ebola outbreaks so far observed and puts
      them in a public health perspective. Damage on the local level has been
      devastating at times, but was marginal on the international level despite the
      considerable media attention these outbreaks received. The potential hazard of
      outbreaks, however, after export of filovirus from its natural environment into
      metropolitan areas, is argued to be considerable. Some avenues for future
      research and intervention are explored. Beyond the obvious need to find the
      reservoir and study the natural history, public health strategies for a more
      timely and efficient response are urgently needed.

PMID- 10886794
TI  - Isolation and partial characterization of dengue virus type 2 and 4 strains from
      dengue fever and dengue haemorrhagic fever patients from Mindanao, Republic of
      the Philippines.
AB  - OBJECTIVE: Isolation of dengue virus from dengue fever and dengue haemorrhagic
      fever cases from Mindanao, Republic of the Philippines. METHODS: 12 patients with
      clinically suspected dengue fever (DF) or dengue haemorrhagic fever (DHF)
      presenting in four regional hospitals between August and September 1995 on
      Minadano were enrolled in the study. Dengue virus was isolated by inoculation of
      Vero/E6 or C6/36 cells with patient serum. IgM antibodies were measured using a
      commercial test system. Up to 454 bp of the capsid region and 240 bp of the E/NS1
      gene junction of different viral isolates were sequenced and phylogenetically
      analyzed. RESULTS: Virus could be isolated from seven patients, five isolates
      were typed as dengue virus type 2 and two as dengue virus type 4 by
      immunostaining with monoclonal antibodies or by RT/PCR. Phylogenetic analysis
      confirmed a close relationship of the dengue virus type 2 isolates with viruses
      isolated in the Philippines in 1983 and 1988. CONCLUSION: As observed in studies
      from other parts of South East Asia, dengue virus type 2 was readily isolated
      from dengue haemorrhagic fever cases. Dengue virus type 2 and 4 circulate in
      Mindanao, Philippines, with dengue type 2 being responsible for most of our
      severe DF or DHF cases.

PMID- 10886795
TI  - Outbreak of cutaneous larva migrans in a group of travellers.
AB  - We describe an outbreak of cutaneous larva migrans (CLM) in a group of 140
      holidaymakers to a resort in Barbados and the index case. methods A two-page
      questionnaire was mailed to holidaymakers and 90% responded. results 25.4% of
      respondents developed a rash consistent with CLM. Risk factors for developing the
      illness were younger age and less frequent use of protective footwear while
      walking to the beach. Patients had difficulty in obtaining a correct diagnosis
      during their initial medical consultation and in obtaining medication from
      pharmacies. Efficacious treatments were oral and topical thiabendazole.
      conclusions CLM can occur in a large proportion of people exposed to contaminated
      soil or sand. Protective footwear is effective in reducing infection.
      Thiabendazole is an efficacious treatment.

PMID- 10886796
TI  - Heterogeneity in cyst morphology within isolates of Acanthamoeba from keratitis
      patients in Thailand.
AB  - We isolated Acanthamoebae from the first two keratitis patients identified in
      Thailand in 1988 and 1990. The patients developed decreased vision, severe
      photophobia, severe eye pain and foreign body sensation after minor corneal
      trauma. The lesions included generalized superficial punctate keratitis, stromal
      corneal ulcer with keratic precipitate and uveitis in one case, and corneal ulcer
      with abscess in the other. Both cases were diagnosed by isolation of
      characteristic trophozoites and cysts of Acanthamoeba from corneal tissue by non
      nutrient agar culture method. Based on cyst morphology, A. castellanii and A.
      polyphaga were detected in one case, and A. castellanii and A. triangularis in
      the other. Restriction fragment length polymorphism analysis of mitochondrial DNA
      (mtDNA-RFLP) revealed that each patient harboured a single parasite population.
      One shared mtDNA-RFLP with an authentic strain of A. castellanii, and the other
      gave a new unique pattern. Thus species identification of Acanthamoeba based on
      cyst morphology per se can be arbitrary, and mtDNA-RFLP may be more appropriate
      for accurate species/strain differentiation amongst morphologically heterogeneous
      populations of Acanthamoebae.

PMID- 10886797
TI  - Intramural haemorrhage of the colon.
AB  - Two cases of acute abdominal crisis due to intramural haemorrhage of the colon
      are presented with a review of the literature. One was a 10-year-old Nigerian
      boy; the haemorrhage occurred in the caecum and ascending colon. The other was a
      69-year-old Caucasian woman with a haemorrhage in the colonic splenic flexure and
      descending colon. Both had a one-stage resection with anastomosis. The child
      survived; the woman died two days after the operation. The preoperative diagnosis
      of bleeding colonic lesions remains difficult especially when facilities for
      investigation are scarce. It is re-emphasized that in patients with acute abdomen
      it is not necessary to insist on accurate preoperative diagnosis before offering
      appropriate treatment.

PMID- 10886798
TI  - The epidemiology of human hookworm infections in the southern region of Mali.
AB  - Two surveys of hookworm (Necator americanus) infections, conducted three years
      apart (December 1994 and January 1998) in a village in the Sikasso region of
      Mali, revealed that overall prevalence of infection was 68.7% and 53%,
      respectively. In both years there was a highly significant difference between the
      sexes in the prevalence and abundance of infection, with male subjects carrying
      heavier infections than females. Both prevalence and abundance of infection
      increased with age, although in 1998 there was a strong interaction between sex
      and age, arising from the declining egg counts among 16-20-year-old females and
      the continuing increase among males, reinforced by the subsequent reduction among
      the older males (> or = 61 years) and concomitant increase among females. After
      controlling for the effects of age, sex and their interaction, a highly
      significant positive relationship was detected between faecal egg counts of
      individuals who were examined in both 1994 and 1998 (n = 134), indicating
      predisposition to infection. This relationship remained significant in each of 4
      age classes spanning 7-79 years. The members of some family compounds were shown
      to carry heavier infections than expected whilst others were less infected,
      suggesting compound-related clustering of hookworm infections. The use of
      footwear increased with age but there was no significant relationship between the
      extent of use of footwear and the abundance of hookworm infection. Eyesight
      deteriorated with age and impaired vision was particularly prominent among the
      older sectors of the community, a legacy from the time when onchocerciasis was
      widely prevalent in the region. Although men with partially damaged eyes carried
      lower infections than expected for their age, no overall significant relationship
      was found between quality of vision and hookworm infections. These results are
      discussed in relation to hookworm epidemiology in general and in Mali in
      particular.

PMID- 10886799
TI  - Efficacy of sulphadoxine-pyrimethamine for acute uncomplicated malaria due to
      Plasmodium falciparum in Malawian children under five years old.
AB  - In 1993, Malawi replaced chloroquine (CQ) with sulphadoxine-pyrimethamine (SP) as
      its first-line treatment for uncomplicated malaria in children < 5 years of age.
      To assess the efficacy of SP after 5 years of widespread use, we undertook this
      study at 7 sites in 6 districts of Malawi. Febrile children < 5 years attending
      the outpatient clinics of selected hospitals whose parents consented were
      enrolled in the study if they had an axillary temperature of > or = 37.5 degrees
      C and pure Plasmodium falciparum parasitaemia of >or =2000 asexual parasites/mm3.
      They were then followed for 14 days or until clinical failure. Parasitological
      resistance rates (RII and RIII) ranged from 7% to 19%. Resistance was higher in
      the north than in the central and southern regions, although this difference was
      not statistically significant. Resistance rates were a mean 19% during the rainy
      season vs. 12% in the dry season (P > 0.05). 80% of parasitological resistance
      was at the RII level. Of all children who failed parasitologically (90/641), 84
      (93%) had no fever on day 7 and their mothers did not report them as being ill;
      only 6 of 641 (0.9%) patients met the WHO criteria for clinical treatment
      failure. Regardless of study site, 75% of mothers reported their children as
      having improved by day 3; 90% reported improvement by day 7, and all reported
      improvement by day 14. None of the children experienced any serious adverse
      reactions and none died. We found that after more than 5 years of widespread use
      of SP in Malawi, its efficacy remains acceptable for treatment of uncomplicated
      malaria, and it should therefore be retained as first-line treatment.

PMID- 10886800
TI  - Evaluation of the ICT whole blood antigen card test to detect infection due to
      nocturnally periodic Wuchereria bancrofti in South India.
AB  - The commercially available ICT Card Test for bancroftian filariasis was evaluated
      for its sensitivity and specificity in detecting microfilaria carriers among 189
      individuals each in filariasis-endemic and nonendemic areas in South India, and
      compared to both conventional night blood finger prick thick blood smear
      examination and venous blood membrane filtration. Though the specificity of the
      test was 100% in comparison to both, the sensitivity was 98.5% against the finger
      prick thick blood smear and 71.9 compared to the membrane filtration technique.
      Similarly, the positive predictive value was 100% against both techniques, but
      the negative predictive values were 99.5% against the finger prick thick blood
      smear and 88.3% compared to the membrane filtration technique. The test's lower
      sensitivity compared to the filtration technique requires further investigation.

PMID- 10886801
TI  - Causes of low attendance at national immunization days for polio eradication in
      Bushenyi district, Uganda.
AB  - The purpose of this study was to investigate the factors influencing attendance
      for polio National Immunization Days (NIDs) using the Attitudes-Social-influence
      self-Efficacy (ASE) model as a guiding theoretical framework. The data was
      collected in Bushenyi district of south-western Uganda in 6 focus group
      discussions about outcomes of attendance at NIDs, about who decides on
      attendance, and about attendance barriers and supports. The purpose of NIDs -
      eradicating polio - was not known to the informants. The main reason mentioned
      for attending NIDs and other immunization was to weaken childhood diseases or to
      strengthen the children's capability in fighting diseases, whether they are
      immunizable or not. However, it was strongly believed that the previous NIDs had
      caused a severe malaria epidemic with a very high mortality, and this led to most
      parents not attending the next. Sources of social influence were mostly opinion
      and local leaders in communities, health workers, friends and relatives. Opinion
      leaders who did not immunize their children were said to hinder attendance at
      NIDs by other lay people. NIDs cards, on the other hand, were regarded as
      valuable means of support for attendance. Thus to improve immunization coverage,
      there is need for issuing NIDs cards, for using health education to change the
      belief that NIDs cause malaria, and to encourage local leaders to attend NIDs.

PMID- 10886802
TI  - Willingness to pay for the retreatment of mosquito nets with insecticide in four
      communities of south-eastern Nigeria.
AB  - OBJECTIVES: To determine the willingness to pay (WTP) for the retreatment of
      insecticide-treated nets (ITN) in four malaria holoendemic communities of
      Nigeria. METHODS: Contingent valuation method. The study tool was a pretested
      interviewer-administered questionnaire. Randomly selected households were the
      study units and household heads or their representatives were interviewed by
      locally trained interviewers. RESULTS: Most households were willing to pay for
      annual ITN retreatment in all four communities. The proportion of those willing
      to pay ranged from 79% to 91%. WTP amounts ranged from $0.05 to $5.26. The median
      from the aggregated data from the four communities was $0.21. Multivariate
      analysis showed that many explanatory variables were statistically significantly
      related to WTP for ITN retreatment. CONCLUSION: WTP for ITN retreatment exists.
      The difficulty lies in implementing this. One possibility would be a community
      based ITN retreatment programme.

PMID- 10886803
TI  - Paediatric survival and re-admission risks following hospitalization on the
      Kenyan coast.
AB  - The district general hospital (DGH) is a common feature of health service
      provision in many developing countries. We have used linked demographic and
      clinical surveillance in a rural community located close to a DGH on the Kenyan
      coast to define the use and public health significance of essential clinical
      services provided by it. Of a birth cohort of over 4000 children followed for
      approximately 6 years, about a third were admitted to hospital at least once.
      Significantly more children admitted with major infectious diseases such as
      malaria and acute respiratory tract infections were readmitted with the same
      condition during the surveillance period than would have been expected by chance.
      Among surviving admissions, mortality post-discharge was significantly higher
      than in the cohort which had not been admitted within 3, 6 and 12 months. Most of
      the patients who died after discharge had been admitted with a diagnosis of
      gastroenteritis. Most children admitted to the DGH survive hospitalization and
      the remaining period of childhood. Despite no clinical trial evidence to support
      the claim, it seems reasonable to assume that in the absence of intensive
      clinical management provided by a DGH, a significant proportion of these children
      would not have survived. However, the DGH is able to define a group of at-risk
      children who re-present with severe complications of infectious disease, and of
      these several may have underlying conditions not amenable to DGH intervention and
      continue to have a poor prognosis. Both groups of children represent
      statistically significant subsets of a rural paediatric community and the future
      organization and co-ordination of DGH and primary care services need to work in
      unison to strengthen the service needs of children at risk.

PMID- 10886804
TI  - Tribute to Dr. Katenga Bonzali.

PMID- 10886805
TI  - The more we know, the less we understand?

PMID- 10886806
TI  - Recombinant human platelet-derived growth factor-BB (becaplermin) for healing
      chronic lower extremity diabetic ulcers: an open-label clinical evaluation of
      efficacy.
AB  - Topically applied recombinant human platelet-derived growth factor-BB
      (becaplermin) is a new pharmacologically active therapy for chronic, neuropathic,
      lower extremity diabetic ulcers. In previous studies, becaplermin gel was
      administered once daily but dressings were changed twice daily. In the present
      study of 134 patients with diabetes mellitus and full thickness lower extremity
      ulcers, dressings were changed only once per day, simplifying the treatment
      regimen. Efficacy criteria included the percentage of patients achieving complete
      healing within the 20-week treatment period, the time to achieve complete
      healing, the rate of ulcer recurrence during the 6-month period following
      healing, and treatment compliance. Complete healing of ulcers was achieved in 57.
      5% of patients, with a mean time to closure of 63 days and a recurrence rate of
      21% at 6 months. Of the potential factors affecting ulcer healing, only drug
      compliance (p < 0.001), dressing compliance (p < 0.01), the presence of infection
      (p < 0.01), baseline ulcer area (p < 0.05), and baseline total wound evaluation
      score (p < 0.05) were significantly associated with healing. Results of this
      study further confirm the efficacy and safety of becaplermin gel for the
      treatment of lower extremity diabetic ulcers.

PMID- 10886807
TI  - The accuracy of using a wound care specialty clinic database to study diabetic
      neuropathic foot ulcers.
AB  - Few epidemiologic studies have examined the effect of clinical risk factors on
      the probability that a patient with a chronic wound will heal or develop another
      wound. Curative Health Services maintains one of the few databases that contain
      detailed patient record information on patients with chronic wounds. The purpose
      of this study was to evaluate the reliability and validity of using this database
      to study individuals with diabetic neuropathic foot ulcers. 154 patient medical
      records were randomly selected from the database and abstracted using a
      standardized questionnaire and protocol. We assessed three key variables:
      diagnosis of diabetic neuropathic foot ulcer, whether the patient healed, and if
      the patient received an autologous product called platelet releasate. These
      variables in the database very accurately agreed with the information in the
      patient medical records, with positive predictive values of 98% (95% confidence
      interval [0.89, 0.99]), 93% (95% confidence interval [0. 68, 0.99]), and 100%,
      respectively. We have shown that, with respect to these three variables, the
      database is very accurate when compared to the medical record. It therefore
      represents a valuable tool with which to study patients with diabetic insensate
      foot ulcers.

PMID- 10886808
TI  - Duration of surgery and patient age affect wound healing in children.
AB  - The migration of inflammatory cells into a wound and their subsequent changes
      during wound healing are essential for the complex processes of tissue repair to
      occur. The aim of this work was to investigate the number of wound leukocytes
      during early wound healing at different time periods in children. Wound cells of
      184 children aged 0-15 years, operated on for a benign disease in the lower
      abdominal region, were harvested with the Cellstick(R) device. The device was
      removed from the wound at 3, 6, or 24 hours after surgery and differential cell
      counts were performed. The cellular patterns were significantly influenced by the
      age of the patient and by the duration of the surgery. The proportions of
      neutrophils, lymphocytes, and monocytes changed significantly from 3-24 hours.
      Our results suggest that there is a distinct time-related change in the pattern
      of inflammatory cells in the early phase of wound healing in children. This
      pattern is affected by the age of the child and by the duration of the surgery.

PMID- 10886809
TI  - Incisional wound healing in transforming growth factor-beta1 null mice.
AB  - Expression of endogenous transforming growth factor-beta1 is reduced in many
      animal models of impaired wound healing, and addition of exogenous transforming
      growth factor-beta has been shown to improve healing. To test the hypothesis that
      endogenous transforming growth factor-beta1 is essential for normal wound repair,
      we have studied wound healing in mice in which the transforming growth factor
      beta1 gene has been deleted by homologous recombination. No perceptible
      differences were observed in wounds made in 3-10-day-old neonatal transforming
      growth factor-beta1 null mice compared to wild-type littermates. To preclude
      interference from maternally transferred transforming growth factor-beta1,
      cutaneous wounds were also made on the backs of 30-day-old transforming growth
      factor-beta1 null and littermate control mice treated with rapamycin, which
      extends their lifetime and suppresses the inflammatory response characteristic of
      the transforming growth factor-beta1 null mice. Again, no impairment in healing
      was seen in transforming growth factor-beta1 null mice. Instead these wounds
      showed an overall reduction in the amount of granulation tissue and an increased
      rate of epithelialization compared to littermate controls. Our data suggest that
      release of transforming growth factor-beta1 from degranulating platelets or
      secretion by infiltrating macrophages and fibroblasts is not critical to
      initiation or progression of tissue repair and that endogenous transforming
      growth factor-beta1 may actually function to increase inflammation and retard
      wound closure.

PMID- 10886810
TI  - Epidermal growth factor and keratinocyte growth factor differentially regulate
      epidermal migration, growth, and differentiation.
AB  - Various growth factors such as epidermal growth factor and keratinocyte growth
      factor have been reported to promote wound closure and epidermal regeneration. In
      the present study epidermis reconstructed on de-epidermized dermis was used to
      investigate the effects of epidermal growth factor and keratinocyte growth factor
      on keratinocyte proliferation, migration and differentiation. Our results show
      that epidermal growth factor supplemented cultures share many of the features
      which are observed during regeneration of wounded epidermis: a thickening of the
      entire epidermis, an enhanced rate of proliferation and migration, and an
      increase in keratin 6, keratin 16, skin-derived antileukoproteinase, involucrin
      and transglutaminase 1 expression. The increase in transglutaminase 1 protein is
      accompanied by an increase in the amount of active transglutaminase 1 enzyme.
      Surprisingly no increase in keratin 17 is observed. Prolonging the culture period
      for more than two weeks results in rapid senescence and aging of the cultures. In
      contrast, keratinocyte growth factor supplemented cultures have a tissue
      architecture that is similar to healthy native epidermis and remains unchanged
      for at least 4 weeks of air-exposure. The rate of proliferation and the
      expression of keratins 6, 16 and 17, skin-derived antileukoproteinase, involucrin
      and transglutaminase 1 is similar to that found in healthy epidermis and
      furthermore keratinocyte migration does not occur. When the culture medium is
      supplemented with a combination of keratinocyte growth factor and a low
      concentration of epidermal growth factor, skin-derived antileukoproteinase,
      involucrin and keratins 6, 16 and 17 expression is similar to that found in
      cultures supplemented with keratinocyte growth factor alone and in healthy
      epidermis. Only high transglutaminase 1 expression remains similar to that
      observed in cultures supplemented with epidermal growth factor alone. Our results
      show that the regulation of keratinocyte growth, migration and differentiation
      depends on the availability of these growth factors. Epidermal growth factor may
      play a dominant early role in wound healing by stimulating keratinocyte
      proliferation and migration while keratinocyte growth factor may play a role
      later in the repair process by stabilizing epidermal turnover and barrier
      function.

PMID- 10886811
TI  - Acceleration of full-thickness wound healing in normal rats by the synthetic
      thrombin peptide, TP508.
AB  - Thrombin is an essential factor in hemostasis, inflammation, and tissue repair.
      The synthetic thrombin peptide, TP508, binds to high-affinity thrombin receptors
      and mimics cellular effects of thrombin at sites of tissue injury. Treatment of
      full-thickness excisional wounds in normal rats with a single topical application
      of 0.1 microg TP508 (14 pmol/cm2) reproducibly accelerates wound closure,
      yielding wounds that on average close 39% more than controls by day 7 (p <
      0.001). Wounds treated with 1.0 microg TP508 are 35% and 43% (p < 0.001) smaller
      than controls on day 7 and 10, respectively. The early rate of closure is
      approximately 40% greater in TP508-treated than vehicle-treated wounds (20 versus
      14 mm2/day) and remains higher through day 7. Breaking strength after closure is
      slightly greater (15-23%) in wounds treated with TP508 than with saline alone.
      Histologic comparisons show that TP508 enhances recruitment of inflammatory cells
      to the wound site within 24 hours post-injury. TP508 treatment also augments
      revascularization of injured tissue, as evidenced at day 7 by the larger size of
      functional vessels in the granulation tissue and by the directed development of
      blood vessels to wounds. These studies raise the possibility that TP508 may be
      clinically useful in management of open wounds.

PMID- 10886812
TI  - Interleukin-8 levels and activity in delayed-healing human thermal wounds.
AB  - There are numerous causes for slow or delayed wound healing. Because slowly
      healing wounds are often inflamed, we quantitated the inflammatory chemokine,
      interleukin-8, produced by slowly healing human burn wounds and compared this to
      interleukin-8 from healed wounds and normal intact skin. Interleukin-8 levels
      were increased significantly in unhealed wounds (19.7 ng/ml) compared to healed
      wounds (7.7 ng/ml) or normal skin (5.7 ng/ml). Interleukin-8 in these ranges was
      added to adult human keratinocytes and fibroblasts. Interleukin-8 significantly
      decreased keratinocyte replication but had no effect on fibroblast replication.
      The rate or final degree of fibroblast populated collagen lattice contraction was
      inhibited at interleukin-8 concentrations between 10 and 30 ng/ml, but not
      altered at concentrations below 10 ng/ml and above 100 ng/ml. The concurrent
      application of indomethacin at 10 microg/ml reversed this interleukin-8 induced
      inhibition. Interleukin-8 inhibited myosin ATPase activity, apparently by
      reducing the phosphorylation of nonmuscle myosin light chain. We conclude that
      elevated levels of interleukin-8 may be found during delayed healing, and these
      elevated interleukin-8 levels may directly contribute to retarded wound closure.

PMID- 10886813
TI  - Mechanical loading regulates protease production by fibroblasts in three
      dimensional collagen substrates.
AB  - Mechanical loading is important in tissue formation and remodelling, notably in
      wound repair. The aim of this study was to measure the effects of controlled
      loading on the release of extracellular matrix protease activities by
      fibroblasts. Fibroblast populated collagen lattices were subjected to external
      cyclical loads through a computer controlled unit incorporated into a culture
      system, a tensioning-Culture Force Monitor. Cyclical loading was compared to
      untensioned and statically loaded gels (tethered endogenous contraction). Overall
      changes in a range of protease activities were monitored (chiefly by zymography)
      as measures of the cyto-mechanical response to these loads. Under static load,
      2.5- and 13-fold more matrix metalloproteinase-2 was produced than matrix
      metalloproteinase-9, at 24 and 48 hours. Total matrix metalloproteinase-9
      increased 37 fold on cyclical loading. Total matrix metalloproteinase-3 and
      urokinase plasminogen activator activities were dramatically reduced on cyclical
      loading while tissue type plasminogen activator activity was increased.
      Comparison with cell responses on stiffer substrates (collagen sponges)
      identified similar matrix metalloproteinase responses to load, but at much
      reduced levels (4-6 fold matrix metalloproteinase-9 stimulation on loading),
      showing the importance of matrix compliance to this mechano-response. In
      conclusion, physiological mechanical loading of fibroblasts in three dimensional
      collagen lattices elicited complex and substantial changes in matrix modifying
      proteases. These changes suggest that cells switch between expression of
      comparable protease activities mainly influencing cell-matrix interactions
      associated with migration or more generalized extracellular matrix remodelling.

PMID- 10886814
TI  - Duration and orientation of mechanical loads determine fibroblast cyto-mechanical
      activation: monitored by protease release.
AB  - Regulation of mechanical force on and by connective tissues is increasingly
      regarded as a critical factor in understanding their function. The aim of this
      study was to identify quantifiable characteristics of external loading to which
      fibroblasts were sensitive. Specific patterns of uniaxial tensile loading were
      applied to fibroblast populated collagen lattices through a computer controlled
      driver: tensioning-Culture Force Monitor. Ramp loads of 120 dynes were applied
      over 10 minutes and 11 hours, and the effect of high and low strain pattern
      changes, with orientation relative to the applied load were investigated by using
      two lattice configurations, high and low aspect ratios, with loads applied across
      the long and short axis. Both, ramp loading and lattice orientation were tested
      in comparison to statically loaded gels. Changes in protease production were
      measured to indicate which loading patterns produced cell stimulation. Greatest
      cell responses were with the slowest rate of ramp loading and unloading (11
      dynes/hour) with the 11 hour ramp causing a 5-fold increase in MMP-9 release.
      Similarly, the greatest stimulation was produced in high strain, aligned High
      Aspect Ratio lattices with a 2.6-fold increase in MMP-9 release. In conclusion,
      duration over which cells are loaded rather than the rate and alignment of that
      loading are both critical factors in cyto-mechanical activation.

PMID- 10886815
TI  - [Public Health: a priority for investment]

PMID- 10886816
TI  - [Historical times, physical times, epidemiological times: probable contributions
      of Fernand Braudel and Ilya Prigogine to epidemiological thinking]
AB  - The text is an approach on time as a scientific category in epidemiology.
      Considering the aphorism time-place-person, time is pointed out as an element
      with little theoretical concern, despite its presence in main epidemiological
      concepts. While a topic connected to important changes in other disciplines, such
      as history, geography, biology and physics, time represents an interesting point
      of view to the interdisciplinary dialogue and its relevance for a critical
      knowledge in epidemiology. To argue about this idea, the historical and physical
      time constructions of Fernand Braudel and Ilya Prigogine are presented. These
      time theoretical constructions are compared with a probable epidemiological time.
      Finally, using the emerging infectious diseases as an example, some
      considerations are made about an apparent epistemological inadequacy of the
      epidemiological time to recognize the social and historical aspects involved in
      the complexity of the disease expressions in human populations.

PMID- 10886818
TI  - [Debate on the paper by Gil Sevalho]

PMID- 10886817
TI  - [Debate on the paper by Gil Sevalho]

PMID- 10886819
TI  - [Debate on the paper by Gil Sevalho]

PMID- 10886820
TI  - [Debate on the paper by Gil Sevalho]

PMID- 10886821
TI  - [Debate on the paper by Gil Sevalho]

PMID- 10886822
TI  - [Debate on the paper by Gil Sevalho]

PMID- 10886823
TI  - [Debate on the paper by Gil Sevalho]

PMID- 10886825
TI  - [The author replies]

PMID- 10886824
TI  - [Debate on the paper by Gil Sevalho]

PMID- 10886826
TI  - Out-patient drug treatment of pneumonia among children under two years of age in
      Fortaleza, Brazil.
AB  - Results are reported from a study on drug use in treatment of children with
      pneumonia in a pediatric hospital in the city of Fortaleza, Northeastern Brazil.
      There were 171 out-patients; prescription details were obtained for 149. The most
      commonly prescribed antimicrobial drug was procaine penicillin, accounting for
      33% of antimicrobial prescriptions, followed by benzathine penicillin (31%),
      ampicillin or amoxicillin (12%), and cotrimoxazole (8%). Benzathine penicillin
      was frequently given with other drugs, but was the sole antimicrobial agent for
      31 children. Compliance with antimicrobial treatment was 52% overall and was
      higher for the injectables. Prescription patterns varied from child to child, and
      children were often prescribed more than one antimicrobial in the same or repeat
      prescriptions; combining this information with compliance, 81 (54%) of the
      children were estimated to have received 5 or more days of appropriate
      antimicrobial treatment for pneumonia. This percentage is not high, and five days
      were often reached after using more than one antimicrobial and after repeat
      visits. The authors concluded that the need remains for simple antimicrobial
      regimes, attractive to comply with, that can be expected to be consistently used.
      Other drugs were chiefly analgesics and bronchodilators.

PMID- 10886827
TI  - Scorpion poisoning in the Acosta and Caripe Counties of Monagas State, Venezuela.
      part 1: characterization of some epidemiological aspects.
AB  - Scorpion poisoning was surveyed in Acosta and Caripe counties, located in the
      Turimiquire subregion of Monagas State, Venezuela, aiming to expand information
      on stings by characterizing some epidemiological aspects. From 1987 to 1993, 298
      cases of scorpion stings were recorded in Acosta and Caripe counties. Acosta had
      212 cases, with an annual incidence rate of 18.3 (cases per 10,000 inhabitants)
      and a period median incidence rate of 128 . The scorpion poisoning index is 4.18
      times greater in Acosta than in Caripe, confirming the former as a hyperendemic
      zone for this type of injury, with a phenomenon of cyclical temporal fluctuations
      and an upward trend. This area is infested with scorpions of the genus Tityus.
      Our results show that the region surveyed in Monagas State is endemic for
      scorpion stings, posing a major public health problem.

PMID- 10886830
TI  - [External quality assessment in coproparasitology in Havana City Province, Cuba]
AB  - An external quality assessment in coproparasitology was carried out in 77
      laboratories from Havana City. A questionnaire and ten plastic vials with
      different intestinal parasites in a small nylon bag, duly sealed, were sent to
      each laboratory. Answers were collected during the 72 hours after delivery.
      Results were analyzed by means of a computer program. The majority of the
      laboratories (70%) passed the test; the municipalities with the worst scores in
      the province were Lisa, Marianao, and Habana del Este. Better results were
      obtained among technologists working only in parasitology than those who were
      also performing other laboratory work, and better averages were observed in
      hospitals than in polyclinics. The best identified intestinal protozoan was
      Giardia lamblia and the worst identified was Blastocystis hominis (with a 61%
      mistake rate), followed by Endolimax nana (24.6%), and Entamoeba histolytica
      (22%). Among helminths, the best identified was Trichuris trichiura (9.2% mistake
      rate) and the highest percentage of incorrect diagnoses was for Taenia sp. and
      Fasciola hepatica (both with 66.2%). Taking into account these results, we feel
      it is necessary to provide training in parasitology among these laboratories.

PMID- 10886831
TI  - [The strategic management: the methodology applied by the "Centre Hospitalier
      Regional Universitaire"]
AB  - This work is a general presentation of the "Demarche Strategique", a strategic
      process applied by the "Centre Hospitalier Regional Universitaire" (CHRU) at
      Lille, France. The hospital management methodology relies on the strategic
      analysis of the best alternatives for rationalizing the hospital mission. It
      takes into account a competitive environment, in which it is necessary to
      structure health care networks based on the negotiation of inpatient care goals.
      The author presents the phases and main methodological tools of the approach, as
      well as a preliminary evaluation of its potentials.

PMID- 10886832
TI  - [Health councils, intergovernmental commissions, and interest groups in the
      Unified Health System]
AB  - Health councils have developed in Brazil in keeping with arrangements under the
      1988 Constitution, and the logic of their political consensus has expanded among
      interest groups relevant to public policy. Collegiate bodies, such as
      intergovernmental commissions, represent an extension of that logic to executive
      relationships and also express political intermediation by expertise, following
      the tradition of the European Welfare State. The state technical bureaucracy has
      thus developed a remarkable role in policy-making and in State-level modeling of
      interest groups. This article argues that such collegiate bodies should be
      analyzed through State action and defines two models for health councils. One,
      the vocal political model, is characterized by a prevalence of outspoken
      denunciation and an overload of demands on the political agenda. The other, the
      consensus model, expresses self-limitation amongst interest groups in drafting
      demands. These models are not hierarchically fixed and are usually linked to the
      political platforms of interest groups participating in the collegiate bodies.

PMID- 10886833
TI  - [Psychiatric institutions and communities: a study of the demand for mental
      health care in the State of Sao Paulo, Brazil]
AB  - Psychiatric hospitals have been accused of being both ineffective institutions
      and the main parties responsible for the chronic status of the mentally ill.
      However, there is a lack of research on the influence of mental health care
      facilities on either the communities in which they are located or the nearby out
      patient services. Their presence may be a cause for increased psychiatric demand.
      This study investigates a possible association between the existence of such
      hospitals in given communities and an increase in hospitalization and demand for
      primary care services. The author compares the demand and client profile of out
      patient services in similar communities, both with and without psychiatric
      hospitals Some evidence was found that in communities with such hospitals there
      is an increase in both hospital admittance and consultations in mental health
      care.

PMID- 10886834
TI  - [Concepts in social research: links with the field of health services evaluation]
AB  - This paper discusses theories and research perspectives from the social sciences
      and their role in constituting the field of "health services evaluation". The
      objective is to present less explored theoretical fields such as the
      "comprehensive" and "dialectical" approaches. Finally, the study presents a
      methodological proposal based on a qualitative approach to the evaluation of
      health services and projects.

PMID- 10886835
TI  - [Becoming a scientist: the perspective of Bruno Latour]
AB  - The purpose of this article is to raise some points for an understanding of
      contemporary French philosopher Bruno Latour's perspective on the
      professionalization process for scientists. We review part of the sociological
      literature that has attempted to conceptually differentiate occupations from
      professions. We thus intend to establish a number of comparative parameters for
      such concepts. The field of knowledge and its role in the stages of the
      professionalization process assume an important place in this reflection.

PMID- 10886836
TI  - [Seroepidemiological survey for influenza virus in Belem, Para, Brazil, 1992
      1993]
AB  - A seroepidemiological study was carried out from 1992 to 1993 to estimate the
      prevalence of antibody to prevailing influenza virus strains circulating among
      patients attending the IEC Virology Laboratory in Belem, Northern Brazil. A total
      of 179 (11%) of serum samples were obtained during the post-epidemic period and
      processed by the hemagglutination inhibition test against the A/Taiwan/1/86
      (H1N1), A/Beijing/353/89 (H3N2), and B/Yamagata/16/88 types of influenza virus.
      The serological results indicate circulation of viruses antigenically related to
      all three strains during the two-year study period. In 1992, the overall
      prevalence rates of HI antibodies to H1N1 and H3N2 were 84% and 56%,
      respectively. Presence of antibodies to both strains was detected in all age
      groups, suggesting intense viral activity that year. Antibodies to influenza B
      were detected at lower levels in all patients during this period. Similar
      prevalence to the H1N1 virus was noted in 1993, indicating that this strain
      occurred in both years. However, an increase in prevalence rates for the H3N2
      virus was seen in 1993, suggesting that this strain (or a related virus)
      circulated intensively during this year. Influenza B activity also increased in
      1993, causing infection mainly among young adults.

PMID- 10886837
TI  - [Community health centers: an alternative for the health system]
AB  - Reflecting on the current reorganization of the relationship between the state
      and civil society, the health care field is involved in an intense debate over
      the organization and use of government and private health services. The authors
      propose an alternative, consisting of the implementation of primary health care
      clinics, managed by local institutions and funded by the Unified Health System.
      To support this proposition, they report on the current experience at the Rocinha
      slum in Rio de Janeiro, where a community health center was built by the
      neighborhood association 12 years ago and has been managed by the community since
      then. The hospital referral rate at the clinic, requests for laboratory tests,
      and use of precriptions have been considerably limited, although these services
      are available. These low rates are attributed to the possibility of closer social
      control by the community, as well as to the geographical features of the center,
      favoring a broader perception of both health problems and treatment. In order to
      provide more substantial support to the proposed centers, some suggestions are
      presented, like the implementation of direct agreements between the government
      and neighborhood associations (not allowed under current legislation) and
      expanding potential sources of funding for the health centers, currently
      restricted to government programs.

PMID- 10886838
TI  - [Nutritional status of children ten years of age or under in a settlement
      organized by the "Landless Peasants' Movement" in Porto Calvo, Alagoas, Brazil]
AB  - This study describes the nutritional status of 357 children (0-10 years) living
      in Fazenda Conceicao, an area occupied by the "Landless Peasants' Movement" and
      recently expropriated for land reform purposes by the Brazilian National
      Institute for Land Settlement and Agrarian Reform. The prevalence of nutritional
      deficits (Z < -2 standard deviations from the NCHS median anthropometric
      standard) relating to body- weight-for-age, height-for-age, and body-weight-for
      height were the following, respectively: 19.6%, 39.8%, and 2%, thus higher than
      the figures published recently for the rural areas of the State of Alagoas as a
      whole (8.4%, 22.7%, and 1.3%). These findings suggest that children are these
      affected by dwarfism. Despite this condition being widely acknowledged as one of
      the most visible manifestations of malnutrtion in developing countries, it is
      important to stress that the concentration of land tenure, an integral part of
      the income-concentrating development model adopted by Brazil, is also a major
      factor in determining such a health profile. There is thus an urgent need for
      policy-makers to reallocate resources for immediate intervention in such farm
      communities, in order to reduce the dire consequences of a situation of this
      magnitude.

PMID- 10886840
TI  - [A conversation with Frederico Simoes Barbosa]

PMID- 10886839
TI  - [A critical analysis of medical specialities and strategies for their integration
      into the Unified National Health System in Brazil]
AB  - The implementation of medical specialization in Brasil has been relatively free
      of constraints. There has thus been a progressive fragmentation of medical work.
      The so-called root specialities are losing both their strength and clinical
      problem-solving capacity. Two operational concepts are proposed for achieving
      better administration of medical responsibilities and the role of medical
      professionals: 1) field of competence and 2) core competence. General goals are
      suggested for reforming specialized training and integration of specialists into
      the Unified National Health System.

PMID- 10886841
TI  - [Renewing the Health for All Strategy]

PMID- 10886842
TI  - [Citizenship and modernity: the emergence of the social issue on the public
      agenda]
AB  - The guiding thread of this article is the inclusion of the so-called "social
      issue" on the public agenda from modernity through its more current developments.
      The study seeks to demonstrate that one of the meanings of modernity is precisely
      the radical inversion of the meaning of public and private, providing for the
      broadening of public space. Far from being associated with a given bourgeois
      capitalist model, modernity thus projects itself as a reinvention of rights,
      citizenship, and contemporary democratic experience. Over this long course, the
      individualization process has been seen as a crucial factor for understanding
      both the ideology of modern societies and - paradoxically - the very emergence of
      social sciences. The individualist concept, emphasizing the specificity of modern
      representation of the social sphere, i.e., its characteristic as a self
      instituting society, allows for a broadened understanding of the public domain.
      In this sense, the ideological polarization between liberal conceptions (favoring
      individualism) and Marxist ones (linked to holistic representations of the social
      sphere) should be reviewed, since this polarization has repercussions on the very
      analytical tools used by social sciences.

PMID- 10886843
TI  - [Debate on the paper by Regina Cele de A. Bodstein]

PMID- 10886844
TI  - [Debate on the paper by Regina Cele de A. Bodstein]

PMID- 10886845
TI  - [Debate on the paper by Regina Cele de A. Bodstein]

PMID- 10886846
TI  - [Debate on the paper by Regina Cele de A. Bodstein]

PMID- 10886847
TI  - [Debate on the paper by Regina Cele de A. Bodstein]

PMID- 10886848
TI  - [The author replies]

PMID- 10886849
TI  - Alcohol consumption and pregnancy in the Mexican national addiction survey.
AB  - In 1988, the General Directorate of Epidemiology and the Mexican Institute of
      Psychiatry conducted the first National Addiction Survey (ENA), providing
      regional and national data on alcohol, tobacco, and drug use. The ENA providing a
      subsample of women who have been pregnant at some time in their lives. There were
      5,234 affirmative responses. Women were asked if they had suffered any of three
      adverse outcomes during their last pregnancy: spontaneous abortion, stillbirth,
      and congenital abnormalities. Prevalence of spontaneous abortion was 3.8%,
      stillbirth 1.2%, and congenital abnormalities 1.1 %. Multiple logistic-regression
      models were used to analyze the effect of alcohol consumption on these problems.
      Consumption during pregnancy was related only with the prevalence of congenital
      abnormalities, with prevalence odds of 3.4. Among habitual users during the last
      12 months, oniy women in the highest use category showed an important
      relationship with the three problems mentioned. Follow-up studies on the Mexican
      population are recommended in order to obtain more conclusive findings.

PMID- 10886850
TI  - [Work by shifts in Botucatu, Sao Paulo: a descriptive study]
AB  - In view of the lack of information on shift-work schedules and working
      organization in companies located in Botucatu, Sao Paulo State, we obtained
      initial information on areas of economic activity, number of workers, and work
      schedules from companis by using facsimiles and mailgrams afler receiving a list
      of companies from the directory of the CIESP. To those who confirmed the use of
      work in shifts, a questionnaire with instructions was sent in order to
      characterize how work was organized. There were 42 manufacturing industries among
      66 companies responding to the study. Fourteen companies reported occurrence of
      work in shifts, including 6,541 workers out of 9,502 in the 66 companies. There
      were 2,346 workers with shift schedules on production divisions in the companies
      reporting the existence of shift systems. Eight companies had been using rotating
      shift systems, of which 5 reported rotation schemes with 6 or more consecutive
      night shifts. Two companies notified shift schedules with counter-clockwise
      direction of rotation including 684 workers in production divisions. There were
      systems with single and multiple shifts lasting from 5 to 8 hours and many work
      schedules even with the same length and same number of shifts. This information
      will allow us to evaluate the relationship between shift work, health, and the
      social life of shift workers.

PMID- 10886851
TI  - [The relationship between payment for childbirth care and prevalence of cesarean
      sections in maternity hospitals in Rio de Janeiro: a review of Carlos Gentile de
      Mello's hypothesis]
AB  - The purpose of this study was to compare prevalence of cesarean sections in nine
      private maternity hospitals in the city of Rio de Janeiro in 1968 and 1993,
      seeking to correlate the form of payment with prevalence of cesareans. We
      analyzed 3,413 deliveries in 1968 in nine maternity hospitals, at a time when a
      form of payment called "per service unit" was used. Twenty-five years later,
      these same maternity hospitals were reanalyzed, with a total of 11,065 births.
      These data were from Gentile de Mello (1968) and the Report from the Information
      System on Live Births, by the Rio de janeiro Municipal Health Secretariat. We
      performed a statistical analysis on the proportion of cesareans comparing the two
      years and observed a statistically significant increase in their prevalence in
      1993 as compared to 1968, although payment was nearly equal for childbirth care
      in the two years. The elimination of the "per service unit" payment system and
      the implementation of equal payment for transvaginal and cesarean deliveries
      proved insufficient to decrease the prevalence of cesareans. We suggest that form
      of payment alone does not determine the high prevalence of cesarean sections, and
      that other variables are impacting this phenomenon.

PMID- 10886852
TI  - [Abortion and physicians in training: the opinion of medical students in Mexico
      City]
AB  - This research project explores doctors' views regarding induced abortion.
      Abortion's penalization in Mexico greatly conditions its relevance as a social
      and public health problem. Physicians constitute a professional sector that can
      play an important role in reforming current laws on abortion. As a professional
      group, they have taken a conservative stance towards abortion. Their attitudes
      are to a great extent influenced by the medical training they receive. In this
      article we present results from a survey of 96 medical students from the
      Universidad Autonoma Metropolitana Xochimilco, in Mexico City. Data were
      processed with the SPSS program. Simple frequencies show that students have
      limited knowledge concerning the legal status of abortion and that they tolerate
      it with restrictions and in limited situations. Women students apparently take a
      more conservative stance, but statistical analysis with the c-square test did not
      show significant differences by gender. The article poses the need to modify
      doctors' training in the reproductive health field, allowing future doctors to
      acquire a broader view of health problems related to sexuality and reproduction.
      In the long run, this should also promote a kind of comprehensive health care
      practice in medical services, thus responding more satisfactorily to women's
      needs.

PMID- 10886853
TI  - [Distribution of anemia among preschool children from the semi-arid region of
      Bahia]
AB  - The objective of this survey was to determine the prevalence of anemia and
      potential determinants thereof in 754 children from urban areas of seven small
      towns in the semi-arid region of Bahia. Hemoglobin was measured in 745 children 1
      to 72 months of age. For the 6-to-72 month-old group, hemoglobin < 11.0 g/dl was
      considered anemia (following WHO recommendations) whereas <9.5 g/dl was
      considered severe anemia. The same cutoffs were used for children under 6 months,
      which are the same ones used in clinical-hematology. A mean hemoglobin of 12.1
      g/dl was found, distributed differently according to age groups (p=0.001). The
      study found prevalences of 22.2 % for anemia and 5.8% for severe anemia,
      respectively. Occurrence of anemia varied significantly with age (p=0.001); the
      highest prevalence was 50.0% in children 12 to 23 months of age, followed by
      29.9% in children below 12 months. The association of anemia with mother's
      education (controlled for age) and per capita family income was not statistically
      significant.

PMID- 10886854
TI  - [Schistosomiasis mansoni occurrence in urban territory. 1. A case study of a
      peripheral urban area in Belo Horizonte, Minas Gerais, Brazil]
AB  - This article characterizes the etiological conditions for schistosomiasis mansoni
      in the urban portion of the Greater Metropolitan Area of Belo Horizonte, Minas
      Gerais. Knowledge about this endemic disease is discussed with a clinical focus
      on subjects who lived in endemic areas from 1946 to 1994, taking into account the
      specific indicators for the endemic disease according to the measures adopted in
      its control.

PMID- 10886855
TI  - [Occupational exposure to metallic mercury in the dentist's office of a public
      primary health care clinic in the city of Sao Paulo]
AB  - This paper discusses occupational exposure to metallic mercury among dentists and
      dental assistants, focusing on biological evaluation, effects on heaith, and
      environmental evaluation. Methods included visits to the clinic, hazard maps,
      urinary and environmental mercury measurements, and evaluation of health status.
      Results for the environment and work processes showed that mercury vapor
      concentrations impregnating surfaces and piping varied from 0.001 to 0.051 mg/m3
      in air; occupational exposure with 62.5% of health workers having HgU ranging
      from 10 to 49 mg/l and 37.5% having HgU below 10 mg/l in 1994, while workers'
      previous measures (from 1992) were lower in every single case; an outflow of
      mercury and inadequate amalgamation due to a faulty amalgamator, the need for
      using a piece of chamois to obtain a homogeneous amalgam and remove excess
      mercury; the existence of combined hazards in the environment, and that all
      workers had been exposed since 1992. Results for workers' health showed a
      prevalence of symptoms from lesions to the central nervous system; central
      nervous system signs; and that mild-to-moderate chronic poisoning was found in
      62.5% of workers.

PMID- 10886856
TI  - [Epidemiological research, operational planning, and intervention measures in
      workers' health]
AB  - To improve intervention measures in workers' health involves the adoption of
      approaches aimed at implementing inspection of the workplace, using ethical
      interventions with impact on the Brazilian Health System. Instruments include
      risk assessment, information flows, and identification of workers' morbidity and
      mortality characteristics. Such measures are planned with four operational bases:
      trade unions, production sector, sentinel event, and microregion, establishing a
      new dynamic relationship between epidemiological investigations and health
      interventions aimed at changing the work process associated with occupational
      injuries and diseases.

PMID- 10886857
TI  - [Linear growth retardation and social factors among schoolchildren from the city
      of Osasco, Sao Paulo, Brazil]
AB  - Cases and controls were selected for this retrospective investigation of the
      social determinants of growth retardation, from a Height Census carried out in
      the 1989 school year,involving children attending the first grade of all public
      and private schools in Osasco (in the Greater Metropolitan Area of Sao Paulo,
      Brazil). The cases, totalling 125 children entering school aged 7-8 years old,
      were characterized by a height-for-age index below -2 z score of the NCHS/WHO
      reference. The controls, totalling 139 children entering school at the same age,
      were characterized by a height-for-age index above -1 z score. Socioeconomic
      variables such as family income, head-of-family's level of schooling, mother's
      schooling, environmental sanitation, and housing conditions were significant
      factors associated with the stunting process. Risk of linear growth retardation
      tended to be higher with lower social class (odds ratio = 7.3 for sub-proletariat
      vs. petit bourgeois; p < 0,001 for overall trend), suggesting the biological
      impact of Brazil's economic slowdown during the 1980s.

PMID- 10886858
TI  - [Risks and benefits of genetic screening: the sickle cell trait as a model in a
      Brazilian population group]
AB  - Population screening of asymptomatic heterozygotes for genetic guidance purposes
      is a very controversial procedure due to the risk of labeling, discrimination,
      stigmatization, loss of self-esteem, and invasion of privacy. Effects of genetic
      counseling supplied to blood donors with the sickle cell trait (AS heterozygotes)
      were investigated. Ninety-two AS donors were invited by letter to a free,
      individual orientation session; 66 of them (72%) accepted the invitation. Some
      50% of the individuals brought their wives and children for examination, thus
      allowing identification of several at-risk couples (13%) and children with sickle
      cell anemia (5%). Six months afterwards 43 AS donors (65%) were reevaluated,
      whereby it was observed that the information had been well assimilated. The
      theoretical risks of genetic screening did not appear to be cause for concern in
      most of the cases examined. However, signs of stigma, labeling, discrimination,
      loss of self-esteem, and invasion of privacy were evidenced in a few cases.

PMID- 10886859
TI  - [Epidemiology of meningococcal disease in the city of Rio de Janeiro: changes
      after vaccination against B and C serogroups]
AB  - Meningococcal disease has been a serious public health problem in the city of Rio
      de Janeiro, with high attack rates among younger children, high case fatality
      rates, and predominance of serogroup B. In December 1994 the second vaccination
      drive against B and C meningococcal disease was performed with the objective of
      protecting children ages 6 months to 13 years. A total of 950 thousand children
      received 2 doses of vaccine produced by the Finlay Institute of Cuba. In 1995 a
      change was observed in the disease pattern with a predominance of serogroup C and
      a higher global attack rate, particularly among children under 1 year of age,
      teenagers, and young adults. In vaccinated groups the attack rate was lower than
      in 1994, due to a decrease in serogroup B. No change was observed in the case
      fatality rate.

PMID- 10886860
TI  - [Household infestation by triatomines and human seroprevalence in Empedrado
      Department, Corrientes, Argentina]
AB  - Domestic and peridomestic triatomine colonization, T. infestans infection rate
      and human seropositives to Trypanosoma cruzi in rural areas of Empedrado
      Department, Corrientes, Argentina, were carried out. Methods used in order to
      search the triatomines, to determine them systematically, to obtain their
      infection rates and the human seropositives, were the same applied in a previous
      report. From 100 households characterized, 53.0% had mud walls, laminated zinc or
      cardboard combined with other elements were used in 37.5% of the roofs, and 83.0%
      had earthen floors. Presence of domestic animais sleeping inside houses was
      detected in 91.0% of human dwellings. Domestic infestation by T. infestans was
      29.0% and 1.0% by T. sordida. Other T. infestans entomological indexes recorded
      were: natural infection index = 23, colonization index = 75 and dispersion index
      = 54,5. T. sordida was found in 12.1% of peridomestic structures while T.
      infestans was detected in 2.4%. General prevalence from 298 human sera analized
      by Indirect Hemagglutination and Indirect Immunofluorescence Antibody Tests, was
      32.2%. A high percentage of positive serology (23.7%) was found among 0-10 years
      old, wich represent the age group of higher transmission risk.

PMID- 10886861
TI  - [A malacological survey in city parks in Belo Horizonte, Minas Gerais, Brasil]
AB  - The Greater Metropolitan Area of Belo Horizonte currently contains 18 city parks
      (also known as "ecological parks") with various bodies of water (lakes, springs,
      streams, etc). Initial research in 17 of these parks showed the occurrence of
      intermediate mollusk hosts for Schistosoma mansoni in at least 4. Monthly
      captures done from August 1994 to February 1996 showed the following results for
      these planorbids: Julien Rien Park: 1,145 specimens of Biomphalaria glabrata (2
      to 13 mm); Betania Park: 149 specimens of B. glabrata (4 to 13 mm); Santa Lucia
      Park: 2,431 specimens of B. straminea (3 to 9 mm); and Lagoa do Nado Park: 3
      specimens of B. tenagophila (3 to 10 mm). Visits to the parks will continue, and
      after a diagnosis of each park's situation, control and/or eradication measures
      suitable for each one will be proposed to the municipal authorities.

PMID- 10886862
TI  - Notes on the training of workers in the health sector.
AB  - The following notes attempt to contribute to questions on planning, design, and
      evaluation of training courses for technical personnel in the health sector. The
      authors analyze and compare trainees' views on their courses and point out issues
      related to planning, implementation, and some benefits of training for trainees'
      lives.

PMID- 10886864
TI  - [Equity in the Brazilian Health Care System: a contribution for debate]
AB  - In this article it is discussed some relevant issues in regard to inequalities in
      the consumption of health care services and the construction of more equitable
      health care system in Brazil. The concept of inequalities in health is
      distinguished from the concept of inequalities in the consumption of health care
      services. It is argued that the geographical dimension of health care service
      consumption differs from the social dimension. This implies that a better
      distribution of financial resources between geographical regions acts at the
      level of regional inequalities but might not have a positive impact on existing
      social inequalities. A more equitable system depends on a greater participation
      on the financing of the system of the richer people. It depends on the solidarity
      of the different social groups in society. The present situation of great
      scarcity of financial resources calls for a definition of priorities.
      Nonetheless, it is argued that the establishment of priorities in the
      availability of health care services is an ethical approach only if it is assumed
      to be a transient strategy directed to the construction of a system based in
      universal access for all those in need.

PMID- 10886863
TI  - Periodontal conditions in a 7-19-year-old student population in Araraquara, Sao
      Paulo, Brazil, 1995.
AB  - The Purpose of this study was to assess the periodontal conditions and treatment
      needs in 7-19-year-old Brazilian school children and adolescents enrolled in the
      urban public schools in Araraquara, Sao Paulo, Brazil, in 1995, to provide
      baseline data for monitoring changes in their periodontal status. A sample of
      1,956 school children and adolescents aged 7 to 19 years was examined by two
      examiners previously calibrated using the CPITN (Community Pe riodontal Index of
      Treatment Needs). The results showed that bleeding was the most frequently
      observed periodontal condition in all age groups, with a mean of 3.0 sextants
      affected at age 15. The presence of calculus increased with age. In the 15-19
      year age group, calculus and shallow pockets (3.5-5.5 mm) were observed in 39.8
      per cent and 1.6 per cent of the adolescents, respectively. In order to achieve
      the WHO oral health goal of no more than one sextant scoring GPITN 1 (bleeding)
      or 2 (presence of dental calculus) at age 15, priority should be focused on
      primary prevention programs to benefit the periodontal health of the majority.

PMID- 10886865
TI  - [Who evaluates the indexes?]

PMID- 10886866
TI  - [The ecological issue: science and ideology, or the utopia of a time]
AB  - Our modern concern over the environment brings us to the historical discussion of
      Scientific Rationalism, principally in contemporary western society, where the
      conflict between Man and the Natural World is at its greatest. In an attempt to
      solve this conflict, Ecology, a field of science, stands out riddled with
      problems, seeking to draw subjects from other fields into its own. Following an
      "ecologized world view" (Ecosystemics), some social currents denounce the
      environmental impact of, technological and industrial models, highly pollutant
      and dependent on natural resources, generating the contemporary disorder in our
      biosphere. These movements, following different schools of thought, demand
      changes in society, taking into consideration the present and future state of the
      environment.

PMID- 10886867
TI  - [Debate on the paper by Elmo Rodrigues da Silva & Fermin Roland Schramm]

PMID- 10886868
TI  - [Debate on the paper by Elmo Rodrigues da Silva & Fermin Roland Schramm]

PMID- 10886869
TI  - [Debate on the paper by Elmo Rodrigues da Silva & Fermin Roland Schramm]

PMID- 10886870
TI  - [Debate on the paper by Elmo Rodrigues da Silva & Fermin Roland Schramm]

PMID- 10886871
TI  - [Debate on the paper by Elmo Rodrigues da Silva & Fermin Roland Schramm]

PMID- 10886873
TI  - [Debate on the paper by Elmo Rodrigues da Silva & Fermin Roland Schramm]

PMID- 10886872
TI  - [Debate on the paper by Elmo Rodrigues da Silva & Fermin Roland Schramm]

PMID- 10886874
TI  - [Debate on the paper by Elmo Rodrigues da Silva & Fermin Roland Schramm]

PMID- 10886875
TI  - [Debate on the paper by Elmo Rodrigues da Silva & Fermin Roland Schramm]

PMID- 10886876
TI  - [The authors reply]

PMID- 10886877
TI  - [Validation of "myocardial infarction" as cause of death on death certificates in
      Barquisimeto, Lara state, Venezuela]
AB  - Death rates due to Ischemic Heart Disease (IHD) are widely used to assess
      regional and national cardiovascular health status. However, their validity is
      questionable, essentially because they are based on death certificates (DCs). The
      present study was conducted in the Greater Metropolitan Area of Barquisimeto
      (Lara State, Venezuela), from June 1991 to July 1992. The purpose was to
      establish the validity of the diagnosis of myocardial infarction in DCs of
      intrahospital deaths. Efforts were made to locate all clinical charts and any
      other relevant information. To validate the diagnosis of MI in the DC we used the
      MONICA project criteria. During the study period a total of 247 eligible DCs were
      recorded. Sufficient clinical information was located for 136 cases (55%). The
      results were as follows: definite MI - 62 cases (45.6%); probable MI - 31 cases
      (22.8%); and non MI - 43 cases (31.6%). These results may indicate an
      overestimation of MI death rates of about 32% [95% Confidence Interval = 23.8% -
      39.4%]. Since these data are from a region with an organized cardiovascular
      health system, it is expected that the overestimation for the rest of the country
      may be even higher. Thus, in order to enhance quality and accuracy of DCs, it is
      necessary to develop a system to improve adherence to existing norms for filling
      out and processing such forms.

PMID- 10886878
TI  - [A logistic regression model applied to Chagas' disease]
AB  - The focus of this paper is the application of statistical models to the study of
      socioeconomic conditioning factors in perinatal Chagas' disease conducted in
      Rosario, Argentina. A case (154) and control (158) design was applied to
      investigate socioeconomic and cultural differences in pregnant women in Hospital
      Roque Saenz Pena as to their infection status. Logistic regression models were
      used to evaluate the importance of antecedents linked to the infection and
      socioeconomic and cultural factors for infection status. For pregnant women, the
      importance of antecedents linked to the infection was confirmed and the women's
      level of schooling stood out as the predominant socioeconomic condition
      associated with infection. Log-linear models were used to explore the
      associations between certain explanatory variables. This approach pointed up the
      most relevant associations between such factors and Chagas' disease and provided
      a better understanding of the framework of relationships among them.

PMID- 10886879
TI  - [Adolescents and health. Group-building based on representations of health and
      disease]
AB  - This study explores the presence of different "groups" of adolescents based on
      their representations of health and disease. Concepts traditionally linked to the
      study of subjectivity were incorporated into the building of these "groups". Four
      hundred students participated in the survey. Data were analyzed through multiple
      correspondence analysis, a multivariate approach especially designed to work with
      large numbers of qualitative variables. Eight groups of adolescents were
      detected, described as follows: frightened; tends to close eyes; hypochondriac;
      sensual; happy; embittered; outgoing (looks out on the world); and introspective
      (contemplates own navel). The results highlight the importance of diversifying
      research and interventions focusing on this age bracket.

PMID- 10886880
TI  - [Production of]
AB  - We propose a critical reflection on quality of information concerning violence in
      Brazil, emphasizing some of the main sources of primary data: Public Law
      Enforcement Departments, Police, and Municipal and State Secretaries of Health.
      The city of Rio de Janeiro is taken as a typical "case" in this analysis. The
      hypotheses are: (a) in the process of producing this information, its generation,
      systematization, and dissemination are poor quality, thus becoming banal and
      revealing their discriminatory bias; (b) data are treated as private tools and
      not as a public service, thus reflecting an authoritarian and bureaucratic
      institutional structure. They themselves become a form of (mis)information, void
      of any valid social or political meaning and insufficient to inform society about
      the real expression of violence and to aid in formulating effective public
      policies. Conclusions are as follows: 1) that information on violent events be
      valued from the time it is recorded until it is put to social use: 2) that
      professionals and institutions dealing with the issue transform structures and
      ideas with a view towards an integrated and conscious fulfillment of their social
      roles; and 3) that society organize and work collectively against violence,
      bolstering the value of human life.

PMID- 10886881
TI  - [Schistosomiasis mansoni in urban territory. 2. A theoretical approach to the
      accumulation, concentration, and centralization of capital and the production of
      disease]
AB  - This study discusses the urbanization of schistosomiasis in the Greater
      Metropolitan Area of Belo Horizonte, Minas Gerais, Brazil. The observation that
      schistosomiasis has become endemic in an urban area is discussed using the
      concept of social organization of space as an exercise in providing an
      operational basis for the social and environmental paradigms of collective
      health. Elements from the new world economic order are discussed: the concept of
      socially constructed space, the internationalization of capital, the periphery,
      and the resulting collective disease generation process. Due to the deterioration
      of state health services and the logic of the new world economic order, the need
      for local schistosomiasis control solutions is stressed.

PMID- 10886882
TI  - [Workers' health in Brazilian state constitutions: a comparative analysis]
AB  - This article briefly analyzes the legal measures related to workers' health in
      the various Brazilian state constitutions. It makes a qualitative and
      quantitative comparison of the different provisions based on the presence,
      weight, and relevance ascribed to the issue, using predefined attributes:
      statement of guidelines; production, control, and utilization of information;
      labor intervention; guarantee of rights. The analysis showed legislators' intent
      to allocate power to the Unified Health System in the field of workers' health so
      as to allow for new practices in this area.

PMID- 10886883
TI  - ["Modernity" and polarization of health in Mexico. Living conditions for workers
      and their families]
AB  - This article analyzes the characteristics of the modernization process in Mexico
      and the polarization produced in living and health conditions for the general
      population as well as workers and their families. We studied socioeconomic and
      health indicators for this purpose. Infectious diseases occupy a high percentage
      of general morbidity, yet diseases such as diabetes, hepatic cirrhosis,
      myocardial infarction, malignant tumors, and accidents and violence are also
      serious public health problems as causes of morbidity and mortality. In some
      regions of the country with specific socioeconomic characteristics, polarization
      of health conditions is even more evident, as in the state of Chiapas as compared
      to Nuevo Leon. Deterioration of working conditions and available data on workers'
      health indicate that the latter should be considered a priority group for health
      measures. Such data also show the paradoxical trend of the more severe but less
      frequent work-related accidents and diseases that are subject to compensation as
      compared to the detection of chronic work-related diseases at an advanced stage,
      as well as significant differences in occupational morbidity among different
      branches of manufacturing.

PMID- 10886884
TI  - [The population's knowledge concerning dengue fever, vectors, and control
      measures in Sao Jose do Rio Preto, Sao Paulo state]
AB  - Educational campaigns to inform the population about dengue fever, vectors, and
      related control measures have been carried out since 1985 by health services. In
      order to assess knowledge levels in Sao Jose do Rio Preto, Sao Paulo, a household
      survey was performed with a sample of 537 households in the urban area of Sao
      Jose do Rio Preto, Sao Paulo, in April and May 1995, where the same number of
      women were interviewed with questions about dengue fever, vectors, and control
      measures. Knowledge as displayed was satisfactory, except for that concerning
      hemorrhagic dengue. However, acquisition of knowledge was not followed by
      adoption of necessary control measures was insufficient to decrease infestation
      rates for dengue vectors in the city.

PMID- 10886885
TI  - [Eating practices and behavior in the urban environment: a study in downtown Sao
      Paulo]
AB  - This study focuses on the implications of urban life style on eating habits and
      the related symbolic representations. Theoretical references used to approach the
      food experience are the concepts of social representation and habitus. The
      methodology consisted of a qualitative analysis of interviews with 21
      administrative employees and field observations made at commercial establishments
      in downtown Sao Paulo, such as snack bars and restaurants. Study of eating
      behavior and practices was developed along two planes: food actually eaten and
      food desired. Results were classified into three segments: "ingesting and
      digesting affection", "determinants of social representations of eating
      practices", and "rituals in eating practices". Due to their origin in a domestic
      universe, symbolic aspects associated with food have a strong affective matrix.
      Concrete conditions of the urban environment associated with the subject's
      financial limits establish a structure of values and feelings compatible with the
      subject's possibilities. The study addresses both the abbreviation of food
      rituals and its implications on food behavior as well as features of the present
      urban food pattern.

PMID- 10886886
TI  - [Technical health care models: from the pyramid to the circle, a possibility to
      be explored]
AB  - The technical health care model that portrays the health system as a pyramid with
      ascending and descending flows of users obtaining access to differentiated levels
      of technological complexity within articulated reference and counter-reference
      processes has been conceived as a rationalizing perspective, the merit of which
      would be to provide greater efficiency in the use of resources, in addition to
      universal, equitable access. In practical terms, by assuming that facts occur
      differently than intended under a certain technocratic rationality, the author
      provides some explanations for this "distortion". He also defends the idea that
      the health system would be more adequately thought of as a circle, containing
      multiple "portals of entry" located at several points in the system rather than
      at a presupposed "base". The author also questions the sense of a "top level", a
      kind of expression related to a certain "technological hierarchy" with the
      hospital occupying the apex. At the same time he highlights the health system as
      an entity to be organized focusing on what is most relevant to each user,
      offering the most adequate technology in the right place and at the most
      appropriate time.

PMID- 10886887
TI  - Secular trend in height in enlisted men and recruits from the Brazilian Navy born
      from 1970 to 1977.
AB  - This study presents data from a survey on height trends in Brazilian Navy
      enlisted men and recruits born from 1970 to 1977. The sample consisted of 52,574
      enlisted men and 4,459 recruits ranging in age from 18.00 to 18.99 years. The
      statistical processing employed two-way analysis of variance procedure, simple
      linear regression comparing height and year of birth and multiple analysis
      controlling for schooling (regression coefficient) and the chi-square. The
      results show that enlisted men and recruits displayed height increments,
      characterizing a contemporary process of secular trend. Such increments were also
      present in the country's various macro-regions. The results were compared to a
      recent investigation of a national scope - the National Survey on Health and
      Nutrition (PNSN) - and both enlisted men and recruits displayed higher median
      height than that reported by the PNSN. Level of schooling for individuals in the
      Navy is high, far superior to that of the Brazilian population as a whole. This
      set of data suggests that young men enlisting in the Navy are on average of a
      higher socioeconomic status than the Brazilian population in general, which
      limits possibilities for extrapolating the findings from this research.

PMID- 10886888
TI  - [Prevalence of CAGE-positive secondary school students in Porto Alegre, Rio
      Grande do Sul, Brazil, 1994]
AB  - This study aims to describe the prevalence of CAGE-positive third-year high
      school students in Porto Alegre, Rio Grande do Sul, in 1994. The sample consisted
      of 1,171 students: 598 (51%) from public and 573 (49%) from private schools. We
      found reference to previous alcoholic beverage consumption in 93% of the
      interviewees. The highest prevalence was among male students (p<0.02) and
      students from private schools (p<0.03). Half of the students reported weekly
      consumption, usually when going to parties (60%) and bars (17%). CAGE
      positiveness prevalence was 8.3% overall and 11% among males (p<0.02). When
      variables like gender, age, and socioeconomic status were controlled, there was
      no statistically significant difference between the kind of school and CAGE
      status.

PMID- 10886889
TI  - [Icons for occupational risk maps: a proposal developed with workers]
AB  - The methodology known as the workers' model was used to design risk maps in a
      study performed in the food-processing industry in Pelotas, in the State of Rio
      Grande do Sul in southern Brazil. The various types of occupational risks were
      initially represented by geometric figures, with a size gradient to represent
      intensity. Joint investigation of these icons showed that they had little meaning
      for the workers. In addition, risks from a same group (physical, chemical, etc.)
      but with different impact on health were grouped, thus missing the specificities
      of exposure. As an alternative, and starting from workers' own risk perceptions,
      a set of risk icons was developed. The study was done in three steps involving
      sixty workers, who proposed and selected the most suitable symbols, which were
      subsequently printed on stickers using silk-screen so that the workers could glue
      them on the risk maps. Each risk is represented by one icon, and intensity of
      exposure is defined by color. This paper presents the icons and the process
      involved in designing them.

PMID- 10886891
TI  - [Psychiatric disorders, suicide attempts, lesions and poisoning among adolescents
      treated in an emergency room, Ribeirao Preto, Sao Paulo, 1988-1993]
AB  - An epidemiological study was conducted to determine the occurrence of psychiatric
      and related disorders, according to the International Classification of Diseases,
      among adolescents treated in an emergency room of a teaching hospital in Ribeirao
      Preto, Sao Paulo, Brazil from 1988 to 1993. Adolescents studied represented 23%
      of the cases treated during this period. Neurotic Disorders (300), Suicide and
      self-inflicted Lesions (E950-E959), and Schizophrenic Psychoses (295)
      predominated among females. Signs and Symptoms related to alcohol and drugs (291,
      292, 303, 304, 305), Schizophrenic Psychoses (295) and Neurotic Disorders (300)
      predominated among males. Adolescents studied were predominantly in the 20 to 24
      and 15 to 19 year range, in this order.

PMID- 10886892
TI  - [Premarital examination: a rite of passage in Public Health]
AB  - In the first decades of this century, pre-nuptial examination, designed to
      protect descendants from risks attributed to heredity, worked as a true rite of
      passage in Public Health routine. An educational text concerning this issue is
      discussed.

PMID- 10886893
TI  - [Drug information centre: contribution for rational use of drugs]
AB  - This paper describes the first year experience of a Drug Information Center
      directed to the community, and managed by pharmacysts and pharmacy students from
      the Department of Pharmacy-UFC, in Fortaleza, Brazil. This pioneer experience
      recieves technical assistance from the "Centro Regionali di Informazione sul
      Farmaco-CRIF (Mario Negri Institute Milan-Italy). Those who consult us are
      registered on a codified formullary while individual information, questions and
      prepared answers are introduced on a database. From December 1994 to November
      1995, 246 persons telephoned CIM-UFC for drug information of which 39% were
      medicine users, 32% pharmacysts, 17% patients relatives, 4,5% health students, 4%
      doctors, 0,8% nurses and 2,8% others. The principal questions were related to
      Adverse Reactions (28%) Indications (28%) and Efficacy (18%). The ATC 2nd level
      groups most referred to were vitamins, analgesics and antiinflammatory agents.
      The most frequent problems justifying drug use were classified as: Endocrine,
      nutritional and metabolic diseases and immunity disorders; Symptoms, signs and
      ill defined conditions; Infectious and parasitic diseases. Requests are
      increasing regularly, responding to the mass media campaigns related to drugs and
      active information is provided by bulletins.

PMID- 10886894
TI  - [Lymphatic filariasis: a potentially eradicable disease]
AB  - The recent demonstration that single-dose ivermectin, diethylcarbamazine, or a
      combination of these drugs can profoundly suppress Wuchereria bancrofti and
      Brugia malayi microfilaremia for periods of six months to two years has led to
      renewed hope that transmission can be interrupted and lymphatic filariasis
      eradicated. Based in part on the availability of these new chemotherapeutic
      tools, the International Task Force for Disease Eradication recently identified
      lymphatic filariasis as one of the few diseases that could potentially be
      eradicated. Thus, control programs based on mass treatment (whether supplemented
      or not by vector control) have begun to be implemented in some endemic areas. We
      provide a brief review of available anti-filarial drugs for use in humans,
      including their tolerance and efficacy.

PMID- 10886895
TI  - ["The Geography of Hunger": from regional logic to universality]
AB  - The Geography of Hunger, now the target of reflective reading 50 years after it
      was first published, shows the author' elegant combination of argumentative skill
      and scientific confidence. Josue de Castro's provocative focus is both a new way
      of thinking and acting towards the food and nutritional situation in Brazil and a
      pioneering approach to the issue of collective hunger as a geographically
      universal phenomenon. Based on regional specificities, the book admits that
      partial contributions may help establish a characteristic map of the problem's
      universal nature, thus helping build a different image of Brazil and the world
      and opening up the possibility of constructing a universal plan to combat hunger
      and new perspectives for those seeking to correct regional differences and
      overcome underdevelopment. In this book, which is also a manifesto, Josue de
      Castro reinterprets the role of classical geography, taking into account one of
      the most important explanatory dimensions, i.e., political analysis, to unveil
      the significance and consequences of uneven spatial development. The concepts and
      proposals raised by The Geography of Hunger are alive and provide essential tools
      for critically rethinking Brazilian reality, particularly that of the Northeast.
      On its fiftieth anniversary, The Geography of Hunger is more current than ever
      because of stimulating and disturbing message.

PMID- 10886896
TI  - [Nutritional data: what is available in Brazil?]
AB  - Available nutritional information in Brazil, generated by non-periodic population
      surveys, has scarcely contributed to the development of policies aimed at
      improving the nutritional status of the Brazilian population, although it has
      helped establish the magnitude and distribution of this problem. We suggest that
      data available in the various health information systems be used to feed,
      monitor, and evaluate nutritional policies, for updating and local follow-up
      purposes. Deficiencies in the quality of data available in these health
      information systems can be minimized through validation studies, thus improving
      the information generated by the system as a whole and consequently the quality
      of health care.

PMID- 10886897
TI  - On scientific misconduct.

PMID- 10886899
TI  - [Duplication of Scientific Articles]

PMID- 10886898
TI  - [Building an agenda for collective oral health]
AB  - After visiting 14 cities from Brazil where important efforts to improve the SUS
      (Unified Health System) were being made, the researcher used his main findings to
      propose a participant agenda-building process for collective oral health,
      integrated to the new scope of collective health at the municipal level. He notes
      the strategic role health professionals can play in a new historical proposal for
      Brazilian society.

PMID- 10886900
TI  - [The concept of space in infectious disease epidemiology]
AB  - This article analyzes how space is employed in infectious disease epidemiology,
      with a brief retrospective of the various definitions of space and its
      implications. Emphasis is given to the theory of natural foci of infectious
      diseases formulated by Pavlovsky and the interactions of epidemiology and
      geography.The current problem posed by emerging infections is seen as a
      determinant of the need for further discussion on the concept of space in
      infectious disease epidemiology.

PMID- 10886901
TI  - How well is hypertension managed in the community? A population-based survey in a
      Brazilian city.
AB  - There is usually little information available on how well hypertensive
      individuals are managed at the community level. This survey measured the
      frequency of hypertension in a medium-sized Brazilian city by studying a cluster
      sample of 1657 adults aged 20-69 years. The 328 hypertensives (19.8%) answered a
      questionnaire on the knowledge and management of their condition. Two-thirds were
      aware of their status and more than half were on antihypertensive medication, but
      only one-third had their blood pressure under control. Physicians failed to
      advise a large proportion of their patients about the need to lose weight, take
      exercise, and quit smoking. Although laboratory tests were carried out in most
      patients, fundoscopy and chest X-rays were performed in fewer than 50%. Continued
      care by the same physician was the only factor significantly associated with
      compensated high blood pressure (relative risk for not having continued care =
      1.35; 95% CI = 1.02-1.71). High levels of absenteeism, reduction of the work
      load, and early retirement were found among the individuals with high blood
      pressure.

PMID- 10886902
TI  - [Total mercury in hair: a contribution to the evaluation of mercury exposure
      levels in Pocone, Mato Grosso, Brazil]
AB  - There are some 60 gold-mining sites in the Bento Gomes River basin (Mato Grosso),
      at the border of the Mato Grosso Pantanal (Swamp), where mercury is used to
      agglutinate fine gold particles through amalgamation. During burning of the
      amalgam to release the gold, mercury vapor is lost to the atmosphere, since
      closed systems for mercury recovery are not always used. This study shows the
      results of total mercury analysis in hair from four volunteer groups living in
      Pocone, Mato Grosso, and presents a general environmental description pertaining
      to the presence of mercury in water and sediments from the Bento Gomes River.
      Atomic fluorescence was used for measuring mercury concentrations. The results
      were lower than for other populations from gold-mining areas in Brazil.

PMID- 10886903
TI  - [Studies on space-time disease clusters: concepts, techniques, and challenges]
AB  - Methods for the analysis of space-time clusters have been used frequently in
      epidemiology and public health in recent decades. However, they have generally
      been applied without an appropriate critique of their limits and usefulness. This
      article reviews some of the most important issues involved in improving the
      interpretability and utility of such methods in this context. We begin with a
      brief discussion about the epidemiological meaning of the concept of space-time
      clustering. We then describe five commonly used methods, including the procedures
      for their use. We also present a conceptual and statistical generalization of the
      techniques. Finally, we summarize some important issues for use of these methods
      in epidemiology and public health.

PMID- 10886904
TI  - [Quality of quality: a workers' health perspective]
AB  - In Brazil, new forms of labor organization based on the so-called Japanese
      management model are characterized by the implementation of Total Quality
      Programs, heavily altering relations in the labor force. Pressures brought to
      bear by modernity, such as demand for quality, affect workers and result in
      physical and mental disturbances. A case study focusing on a textile industry in
      Nova Friburgo, Rio de Janeiro State, aimed at elucidating how such programs are
      formulated in such a way as to increase product quality without changing quality
      of life for workers. We detected precarious work conditions alongside
      sophisticated requirements, including abstraction, internalized control,
      dissemination of the supplier/client concept, etc., running up against a labor
      force with limited schooling, thus creating a tense atmosphere with a steady
      speed-up in the work pace, albeit with no real gains for workers.

PMID- 10886905
TI  - [Risk profile: multivariate cluster analysis of urban small areas based on
      socioeconomic indicators - census tracts from the Greater Rio de Janeiro
      Metropolitan Area]
AB  - A method based on small area data analysis was developed to build a health risk
      classification for the Greater Rio de Janeiro Metropolitan Area. The approach
      uses 1991 census data and studies data pertaining to sanitation, ownership and
      type of housing, size and occupancy of the household, demography, schooling, and
      income. Principal component analysis applied over each dimension allowed for the
      choice of 15 variables, which summarized most of the observed variances.
      Additional analysis with these variables suggested that just six variables are
      sufficient for the construction of a classification using k-means method of
      multivariate cluster analysis. Five classes were obtained: (A) high income; (B)
      lower income; (C) poor; (D) low schooling and income; (E) low-level access to
      sanitation. The existing inequality in each of the geopolitical established areas
      was clearly identified. The proposed method allowed for the construction of
      compound indices to evaluate quality of life, based on widespread and easily
      obtained data (the census). Moreover, the method contributed to the detection of
      socioeconomic inequality, identifying, not only the larger poor regions but also
      the small excluded areas.

PMID- 10886906
TI  - [The diaphragm as a contraceptive method in the experience of users in the public
      health services]
AB  - This study, started in August 1989, describes the acceptability of diaphragms as
      part of the daily routine of 194 women enrolled at five public health care
      centers in Osasco, (Greater Sao Paulo). Follow-up of the cohort was performed by
      semestral home interviews until August 1991. Our data indicate that the diaphragm
      can be a viable alternative within the public health care setting. Women,
      including those from low-income groups, are interested in new alternatives to
      currently available contraceptive practices. Nevertheless, the cumulative rate of
      continuity for use of the method was only 25.7% (39 women) after a period of 12
      months. Only 37.1% of women opting for the diaphragm confirm its use during every
      act of sexual intercourse. Most of the women (72.7%) only learned about
      diaphragms during the process of choosing a contraceptive method. The main
      reasons for discontinued use were partners' complaints, discomfort, and
      difficulty in handling. The findings point to the need for reformulating family
      planning activities to provide greater support for women, introduce initiatives
      to enhance male participation, and promote on-going training of health
      professionals with regard to the management of the method and support for its
      users.

PMID- 10886907
TI  - [Physicians and health care: state, market or regulation? A false issue]
AB  - A cost crisis in the health care sector has focused discussion on health care
      services and an assessment of the results of investments in the health sector,
      underlining the importance of medical doctors as key actors in this area. This
      article reviews the main analytical approaches to professionalism in the last
      decade and discusses the most recent paradigmatic shifts. New approaches have
      emerged for correlating the medical division of labor (contained in specialized
      fields which are becoming more and more fragmented) with structural and
      historical changes in the professional market, as well as the collective action
      developed by these interest groups in their relationship to the state. These
      approaches, more closely linked to political economy, have made important
      contributions to this debate, because they allow for a questioning of the kind of
      ideological polarization contained in health care reform proposals aimed at a
      withdrawal of the state and the rule of the market (with no analytical
      justification), in addition to shifting regulation to a position outside the
      historically mutable dynamics between the state, health care providers, and
      clients of the health care sector and the public policy arena.

PMID- 10886908
TI  - [Nitrogen dioxide]
AB  - In order to assess level of human exposure to nitrogen dioxide, 22 traffic police
      from the city of Rio de Janeiro were monitored during their working hours for 3
      consecutive days. Samples were taken by using a passive sampler (badge) and
      analyzed spectrophotometrically after reacting with sulphanilic acid followed by
      coupling with N-naphtilethylenediamine dihydrochloride. Results ranged from 13.3
      to 193.6 mg/m3. According to the literature, these levels are not associated with
      any acute damage to human health but care should be taken to avoid long-term
      problems.

PMID- 10886909
TI  - [Models for physicians' professional regulation in Latin America and theoretical
      elements for its analysis]
AB  - This paper reviews regulation of medical work based on concepts available in the
      specialized literature. It proposes the model developed by Moran and Wood to
      analyze the regulatory process in the Latin American context. However, any
      conceptual model used for the analysis of regulation should consider the changes
      generated by the reform in the interaction between financial and regulatory
      agents and health care providers. The regulatory function is involving an
      increasing number of groups interested in the appropriate performance of health
      services. Regulation of medical work is a dynamic issue requiring close analysis.

PMID- 10886910
TI  - [The labor process and work-related accidents among garbage collectors in Rio de
      Janeiro, Brazil]
AB  - This study describes the work performed by garbage collectors in the Rio de
      Janeiro City Street Cleaning Company (COMLURB) (Rio Comprido division) and its
      consequences for their health. Data were collected through interviews and on-site
      video documentation. A detailed description of the work process was performed. In
      addition, we analyzed the workers' reports of their lifetime experience with job
      related risks and accidents.

PMID- 10886911
TI  - [Characteristics of private health care services in Salvador, Bahia, Brazil]
AB  - To study the organization of private health services in the city of Salvador,
      Bahia, Brazil, a survey was carried out in 1994 involving 174 facilities
      registered at the Brazilian Institute of Statistics and Geography - IBGE. Health
      services characteristics studied were the following: number of physicians,
      hospital beds, production and cost of outpatient services, and legislative
      aspects. Health services were classified according to the amount of resources
      each type of granting agency contributed to support outpatient care. We found
      that the majority (51.1%) of private health care services in Salvador do not
      depend on public funds. The main sources of revenue for health services are
      private health insurance (41.9%) and other kinds of private health plans (54%).
      These changes in the organization of health services challenge health planners to
      review strategies for municipalization of health care and the relations between
      public and private health services in Brazil.

PMID- 10886912
TI  - [Analysis of the work process in health research laboratories: a proposal for
      investigation]
AB  - This article presents a proposal for analyzing the work process involved in
      building technoscientific knowledge in the health field, focusing on the work
      developed by research laboratory technicians in the Oswaldo Cruz Foundation.
      Beginning with an in-depth description of the technicians' laboratory activities,
      we discuss the relationship between the various stages of work and the different
      actors, the technicians' value as actors in the process of building knowledge,
      and various actors' perceptions of how essential this work is. We attempt to
      outline the context in which the work processes in health sciences laboratories
      were incorporated into an analysis of the work process in health. By establishing
      a dialogue with the sociology of science, we present our proposal as an attempt
      to introduce new social sciences approaches for analyzing the work process,
      specifically as applicable to an analysis of work in the health field.

PMID- 10886914
TI  - [Construction of meanings relating to social control with health counselors in
      Piaui state, Brazil]
AB  - This article describes a health education experiment with health counselors in
      two health administration districts in the State of Piaui, Brazil. Focusing on
      the Ministry of Health's Project for Social Control and People's Participation in
      Health, the article analyzes forms and contents pertaining to the issue of social
      control in the health field, under a situation where society is controlled by
      small groups detaining both power and wealth. The experiment showed the
      importance of constructing meanings concerning social control in day-to-day
      relationships between the community and health services and the strategic role of
      health professionals in developing health education activities.

PMID- 10886913
TI  - [Applicability of the strategic planning approach to local health organizations]
AB  - This paper presents the preliminary results from a study on the limits and
      possibilities of the strategic planning approach for local health organizations.
      A comparative analysis is developed between two experiences concerning the
      application of the strategic situational planning method (PES method) in the
      management of a health center and hospital. Questions include the following:
      difficulties with the use of the category actor in local health organizations;
      possibility of drafting a collective project based on the multiple rationalities
      existing in such organizations; possibility of improving communications processes
      with the use of the PES method; difficulties related to organizational culture;
      and low levels of responsibility, as well as difficulties pertaining to the
      method's complexity and the possibility of simplifying it, maintaining strategic
      situational analysis and improving organizations' managerial capacity.

PMID- 10886915
TI  - [Case report of two work accidents investigated using the causal tree method]
AB  - In a large company in Sao Paulo State, two work accidents were investigated using
      the Causal Tree Method (CTM), leading to the accurate identification of factors
      related to work organization as the causal factors for the accidents. These cases
      pointed to the role of organizational factors, such as improvised and temporary
      assignments to work stations and/or jobs, decisions about the performance of
      tasks left to unprepared workers, unavailability of proper tools and/or
      materials, and faulty information distribution within the company. Analysis of
      the accidents allowed for the presentation and discussion of the method (CTM),
      its lengthy application, its demands in terms of training, and its potentialities
      for accident prevention.

PMID- 10886916
TI  - [Epidemiology, values, and the meaning of paradigm]
AB  - Use of the term paradigm has recently reached the epidemiological milieu. This
      article provides a critical analysis of a classification of "epidemiological
      paradigms" as proposed by Almeida-Filho. It was initially ascertained that values
      were not considered fundamental elements for the construction of paradigms, and
      that they therefore distanced themselves from the Kuhnian matrix. Systematization
      sought to unite antithetical tendencies and thus seemed closer to the Foucaltian
      episteme. Finally, hegemony was considered a more appropriate term than paradigm
      for systematizing epidemiological periods, since the values of the different
      watersheds are committed to particularity (principally social class).

PMID- 10886917
TI  - [Sand flies in Timoteo, Minas Gerais, Brazil]
AB  - Sporadic cases of tegumentary leishmaniasis have occurred in Timoteo, Minas
      Gerais State, basically among the rural population. In order to study the
      region's sand fly population, New Jersey light traps were set in seven different
      neighborhoods. Specimens were gathered from June through October 1994, December
      1994, and January through March 1995, with a total of 3,240 hours per trap. A
      total of 4,396 sand flies were captured, distributed among two genera and twenty
      species: Brumptomyia cunhai, Brumptomyia nitzulescui, Lutzomyia (Nyssomyia)
      whitmani, Lutzomyia (Nyssomyia) intermedia, Lutzomyia quinquefer, Lutzomyia
      lenti, Lutzomyia (Pintomyia) fischeri, Lutzomyia migonei, Lutzomyia sallesi,
      Lutzomyia termitophila, Lutzomyia aragaoi, Lutzomyia borgmeieri, Lutzomyia
      (Psathyromyia) lutziana, Lutzomyia (Sciopemyia) sordellii, Lutzomyia (Pintomyia)
      pessoai, Lutzomyia (Trichopygomyia) longispina, Lutzomyia misionensis, Lutzomyia
      (Psychodopygus) davisi, Lutzomyia lanei, Lutzomyia (Pressatia) sp. The species L.
      (N.) whitmani was the most frequent, with 52.12% of the total, followed by L.
      (N.) intermedia with 34.10%, and both may be involved in transmission of
      tegumentary leishmaniasis in the region.

PMID- 10886918
TI  - [Algorithm for establishing hospital admittance data based on the hospital
      information system in the Brazilian Unified Health System]
AB  - The authorization form for hospital admittance (AIH), an observation unit under
      the Hospital Information System of the Unified Health System (SIH/SUS), may
      represent a short-term hospital admittance or a longer hospital stay. This study
      presents an algorithm for composing admittance data based on the AIH forms,
      allowing for a proper assessment of hospital mortality, costs under the Unified
      Health System (SUS), and longer hospital stays, typical of chronic, terminal, and
      psychiatric patients.

PMID- 10886919
TI  - [Stomach Cancer in Brazil: still a major public health concern]

PMID- 10886920
TI  - [Stomach cancer: risk factors]
AB  - For the last fifty years, stomach cancer has become less important in terms of
      morbidity and mortality in developed countries, but the same pattern has not
      occurred in Brazil. The main risk factors for this neoplasm are certain diet
      patterns that became evident through epidemiological studies in various
      population groups. After the carcinogenic effects of nitrosamines and the anti
      oxidant activity of vitamin C were discovered, some of the associations between
      stomach cancer and diet were partially understood. After the description of
      Helicobacter pylori in 1983 and the evidence of the relationship between this
      bacteria and certain stomach diseases, new elements were added to the knowledge
      about the development of this neoplasm. Current knowledge, albeit incomplete,
      provides interesting prospects for the prevention and early diagnosis of stomach
      cancer.

PMID- 10886921
TI  - Implications of Helicobacter pylori infection for stomach cancer prevention.
AB  - Accumulating evidence has implicated Helicobacter pylori, an established cause of
      chronic gastritis and peptic ulcer, in the etiology of gastric cancer. Control of
      this infection would reduce the occurrence of chronic gastritis and peptic ulcer
      and might substantially lower the risk of stomach cancer as well. The public
      health impact of this infectious agent warrants efforts to identify preventive
      measures. This paper reviews the evidence linking H. pylori infection to gastric
      cancer and evaluates the potential for control in high-risk populations. Current
      obstacles to H. pylori control are discussed, including the link to poor
      socioeconomic conditions, difficulty in identifying incident cases, lack of
      natural immunity to reinfection, limited effectiveness of antibiotic therapy in
      high-prevalence populations, and incomplete knowledge regarding the reservoir of
      infection, mode of transmission, host susceptibility factors, and the potential
      for developing an effective vaccine. Worthwhile avenues of research include
      studies designed to identify modifiable risk factors for acquisition of the
      infection, modifiable host factors that may increase resistance to chronic
      infection, more effective antibiotic therapies, and effective vaccines.

PMID- 10886922
TI  - [Environmental risk factors for gastric cancer: the toxicologist's standpoint]
AB  - Carcinogenesis is a highly complex process involving both inherited risk factors
      and environmental ones such as diet, smoking, occupation, and exposure to
      radiation and chemical agents. Experimental toxicology identifies potentially
      carcinogenic chemicals and thus makes it possible to introduce regulatory
      measures aimed at reducing human exposure to them. Carcinogenesis can be viewed
      as consisting of three distinct sequences: initiation, promotion, and
      progression. Neoplastic conversion (initiation) occurs when a genetic event
      (e.g., point mutations, chromosomal rearrangements, insertion or deletion of
      genes, and gene amplification) results in oncogene activation and/or lack of
      expression - or inactivation of products - of tumor suppressor genes. Promotion
      involves clonal expansion of initiated cells and requires cell proliferation.
      Effective strategies for reducing risk of gastric cancer or neoplasias at other
      sites should include both control of known carcinogens and chemical prevention
      through rational interventions in the carcinogenic process. The toxicologist's
      challenge is thus to devise better and less expensive predictive assays and to
      elucidate the mechanisms underlying chemical carcinogenesis.

PMID- 10886923
TI  - [Reliability and accuracy of reported causes of death from cancer. I. Reliability
      of all cancer reported in the State of Rio de Janeiro, Brazil]
AB  - Mortality records are often used in epidemiological studies, particularly in
      cancer studies. This paper aims to evaluate reliability and accuracy of cancer
      mortality data in Rio de Janeiro, Brazil. A systematic random sample of 394 death
      certificates was obtained from a total of 12615 cancer deaths. This sample was
      recoded by an independent codifier. A kappa coefficient of 0.89 (95% C.I. 0.86
      0.92) was obtained to the third digit, which increases to 0.95 (95% C.I. 0.94
      0.96) when restricted to the mortality list used in international publications.
      The positive predictive value was 95.7% for this sample. These results reveal a
      high standard reliability of cancer mortality records in the State of Rio de
      Janeiro making them suitable for use in epidemiological research.

PMID- 10886924
TI  - [Reliability and accuracy of reported causes of death from cancer. II. Accuracy
      of stomach cancer reported in the municipality of Rio de Janeiro County, Brazil]
AB  - Quality of data is a central concern in epidemiological studies, particularly
      when using secondary data. This study aims to carry out on reliability and
      accuracy of stomach cancer mortality data in the city of Rio de Janeiro. A simple
      random sample of 97 death certificates was obtained from a total of 645 stomach
      cancer deaths in 1990, and was used for validation. A questionnaire specifically
      designed to obtain clinical and laboratory data was completed for each case. Two
      physicians read this questionnaire and completed the new death certificates,
      allowing analysis of the instrument's reliability. A total of 86 cases were
      studied as a consequence of 11 losses (11.3%). Reliability analysis of
      questionnaires revealed 90.7% agreement according to stomach cancer diagnosis
      (kappa = 0.73). Accuracy was calculated by positive predictive value: 90.7%.
      Eight cases were discharged after clinical and laboratory revision. The study
      concludes that mortality data by stomach cancer in the city of Rio de Janeiro are
      very reliable, and that their level of accuracy is adequate for use in
      epidemiological studies.

PMID- 10886925
TI  - [Stomach cancer mortality in Brazil: from 1977 to 1989]
AB  - Both incidence and mortality of stomach cancer have been declining in most of the
      world in the last decades. However, this phenomenon has not been studied in
      Brazil. Although data on incidence rates are insufficient, there is a
      standardized historical series on mortality data beginning in 1977. This study
      analyzes trends for stomach cancer mortality during the 1977-1989 period for
      Brazil and Brazilian State capitals, using the standardized mortality rates of
      stomach cancer (standardized population: Brazil-1980). The results showed that
      mortality rates have been decreasing in Brazil as a whole and nearly all of the
      State capitals. However, differences in mortality-rate trends appeared when
      patterns and location of death were analyzed. The decline was most evident in the
      Southeast, South, and Center-West, similar to that of European countries.
      Although stomach cancer is still an important cause of fatal cancer (particularly
      in males), stomach cancer mortality is currently less important than lung and
      breast cancer mortality in these regions. Unfortunately, we lack historical
      incidence series to compare with mortality data to determine whether they reflect
      actual trends in the incidence of stomach cancer in Brazil.

PMID- 10886926
TI  - [Temporal trends from stomach cancer mortality in Rio de Janeiro State: a
      comparison between metropolitan area and interior during 1979 and 1986]
AB  - A decline in stomach cancer mortality has been observed in many countries around
      the world in the last fifty years. In the State of Rio de Janeiro, Brazil,
      stomach cancer was the second most frequent cause of death by cancer among males
      and the third among females during the 1980s. This study presents a simple
      analysis of trends in stomach cancer mortaliy in Rio de Janeiro State by gender
      and residence area during the period from 1979 to 1986. The data showed a general
      decline in stomach cancer mortality for the entire state for both genders during
      the study period. Although mortality rates were higher in the interior than in
      the Greater Metropolitan Area, the decline was less marked in the interior. These
      findings suggest that the classical risk factors for stomach cancer might have
      differentially influenced inhabitants of the two geographic areas, e.g.,
      concerning the role of food preservation. This report points to the need for
      research to identify the main risk factors for cancer to which the population of
      Rio de Janeiro is exposed, addressing the different patterns found in the Greater
      Metropolitan Area and the interior.

PMID- 10886927
TI  - Stomach cancer incidence in Brazil: an ecologic study with selected risk factors.
AB  - Contrary to many industrialized countries in which a sharp decline in stomach
      cancer incidence has been observed, Brazil still shows intermediate to high
      incidence rates. An ecologic analysis was performed to explore variables possibly
      associated with the development of stomach cancer. Cluster analysis, principal
      component analysis, and factor analysis were carried out with population data,
      including the following: stomach cancer incidence rates in the early 1990s
      obtained from population-based cancer registries in Porto Alegre, Campinas,
      Fortaleza, Belem, and Goiania; and data from a Brazilian national survey on
      family expenditures (several diet consumption items and availability of home
      refrigerators) carried out in 1974-75. The results suggested that past
      availability of a home refrigerator, i.e. food preservation, may have played an
      important role in currently observed differences in stomach cancer incidence
      among the various populations studied in Brazil. Differences in living standards
      among populations in these cities also appear to have played an important role in
      the observed incidence differences.

PMID- 10886928
TI  - [Hystological types and mortality for gastric cancer in Sao Paulo, Brazil]
AB  - The objective of this study was to analyze, according to Lauren's classification,
      the prevalence of a hystological type - intestinal or diffuse -, among gastric
      carcinomas. The authors reviewed 650 hystological sections from a Hospital in the
      City of Sao Paulo during a 30-year period, following the definitions of the above
      classification. After the 50's the intestinal type proved to be prevalent,
      reaching 62.74% of all cases of gastric cancer in the 80's, and showing a ratio
      of intestinal/diffuse type of 1.71. Other large series of cases whose diagnoses
      followed the nomenclature of WHO Hystological Classification showed to be
      inadequate for this study. The prevalence of the intestinal type of gastric
      carcinoma seems to disagree with the decreasing rates of mortality due to this
      disease in the State of Sao Paulo, in the same period. Further studies, such as
      the analysis of incidence rates and prevalence of Helicobacter pylori, among
      others, are necessary for a better understanding of these data.

PMID- 10886929
TI  - [Hystopathology of gastric cancer]
AB  - This study draws a random sample (334 individuals) of all patients diagnosed with
      stomach cancer from 1980 to 1995 at the National Cancer Institute in Rio de
      Janeiro, Brazil, and reviews histopathological data. Agreement between previous
      and present classification of the histopathological material (Lauren's
      classification) was considered quite substantial (kappa = 0.65). Based on this
      classification, a statistically nonsignificant trend towards decline in the
      intestinal type of stomach cancer among older individuals (60 years old or older)
      from both genders was observed (males: 41.0% in 1980-1985, 37.9% in 1986-1990,
      and 28.8% in 1991-1995; females: 41.4%, 31.5%, and 15.2%, respectively).
      Proportions of the intestinal type among younger patients from both genders
      remained stable throughout the period.

PMID- 10886930
TI  - [Primary prevention and detection of gastric cancer]
AB  - Stomach cancer, the worl&dacute;s most common malignant neoplasia in 1980, has
      shown a decrease in death and incidence rates in several countries. Still not
      totally elucidated, the decline in incidence and death rates has been attributed
      to environmental factors. It is unlikely that the decline has stemmed primarily
      from changes in either the treatment system or diagnostic techniques. In Brazil,
      stomach cancer has been a major challenge, since the country faces high incidence
      and death rates. In addition, the Brazilian health system lacks the means to
      assume, fund, and develop a stomach cancer diagnostic program. According to
      current knowledge, stomach cancer develops from damage to the gastric mucosa by a
      diet rich in salt, nitrates/nitrites, and possibly carbohydrates. Initiation and
      development can be offset by a sufficient intake of fruit and fresh vegetables.
      Household refrigeration, widespread since the early 20th century, has helped
      people consume fresher, well-preserved food, no doubt generating a major downward
      impact on stomach cancer rates. In present-day Brazil, a national policy aimed at
      stomach cancer control must be based on rebuilding the health system and
      expanding patients' access to it, disseminating information on diet changes, and
      improving socioeconomic conditions.

PMID- 10886931
TI  - Aspects of gastric cancer epidemiology with special reference to Latin America
      and Brazil.

PMID- 10886932
TI  - [Imigration and cancer in Sao Paulo]

PMID- 10886933
TI  - [Editorial]

PMID- 10886934
TI  - [Workers' health: an overview and challenges]
AB  - This article provides an overview of workers' health services in Brazil, the
      context of their emergence, their main guidelines as a social policy since 1980,
      and their development, identifying some difficulties for their implementation. In
      addition, the study points to some challenges for institutions and society as a
      whole in overcoming the crisis in this field.

PMID- 10886935
TI  - [History and dilemmas in the development of the worker's health field]
AB  - This article reflects on the theoretical and practical foundations impacting and
      shaping the field of workers' health in Brazil, as part of the overall field of
      collective health. By analyzing the various forms of approaching the relationship
      between work and health, the paper emphasizes its complex and conflicting nature
      as a central reference for the work process, in keeping with the premises of
      social medicine in Latin America. This focus underscores the need for
      interdisciplinary approaches contemplating and even extrapolating the links
      between areas of knowledge generally ascribed to the field of health. Finally,
      the paper gives a brief diagnosis of the current situation in this field, where
      pending questions join those resulting from globalization of the economy and
      particularly industrial restructuring, in light of which the challenge is raised
      to broaden the objects of study and intervention to include the implications of
      outsourcing, increasingly precarious labor conditions, informal labor, and
      unemployment on the population's health and living conditions.

PMID- 10886936
TI  - [Worker's Health Surveillance]
AB  - This paper is part of a broader discussion on the need for more in-depth study of
      workers' health surveillance practices, which are most often developed
      empirically, without well-defined theoretical or technical foundations. The paper
      presents a concept of surveillance in workers' health as a fulcrum for actions in
      the relationship between the work process and health. It emphasizes the exposure
      based perspective involved in the epidemiological approach. Risk situations and
      effects are placed in spatial and technological context. The model provides an
      interdisciplinary approach with a technological, social, and epidemiological
      basis in a three-dimensional structure. A matrix for planning actions in workers'
      health surveillance is also presented, focusing on the connections between
      effects, risks, territory, and activities.

PMID- 10886937
TI  - [New labor relations and workers' health in Argentina: challenges and
      perspectives for epidemiology]
AB  - This paper analyzes changes in labor relations, legislation pertaining to work
      related diseases and accidents, and the impact on workers' health in Argentina
      (1989-1995). The data indicate an increase in unemployment, underemployment, self
      employment, and new hiring practices. The study shows the mechanisms by which the
      state has delegated responsibility for prevention of work-related risks to the
      private insurance sector. The theoretical discussion of causality thus acquires a
      political/practical dimension. The data show an increase in work-related
      accidents following labor reform. Research by universities, NGOs, and labor
      unions reveal changes in health profiles for salaried, self-employed, and
      underemployed workers. The three National Meetings on Employment and Health (1992
      1994) established an area of exchange between academic and workers' knowledge,
      with some 128 presentations, research projects, and studies, pointing to an
      enhanced field for epidemiological surveillance and intervention. The paper
      reviews the surveys performed by the National Confederation of Workers in
      Education and the Public Employees' Association.

PMID- 10886938
TI  - [Analysis of environmental technological risks: prospects for the worker's health
      field]
AB  - The objective of this paper is to identify theoretical questions and challenges
      for the public health field, especially the field of workers' health, raised by
      technological and environmental risks related to the workplace but going beyond
      it. Using industrial chemical risks as an example, the authors show the
      vulnerability of contemporary societies in handling such risks and the worsening
      situation in peripheral countries. The scope of risk analysis is presented
      according to the engineering, toxicological, and epidemiological approaches as
      well as the critique raised by the social sciences. Science alone cannot solve
      such complex problems as technological and environmental risks. To overcome these
      limits, some theoretical and methodological proposals have been developed by the
      risk analysis and workers' health fields. The authors emphasize the discussions
      on the interdisciplinary, systemic, and participant approaches, incorporating the
      interaction between knowledge and dialogue as fundamental conditions for the
      prevention and control of technological and environmental risks.

PMID- 10886939
TI  - [Work-related accidents: urban violence and death in Porto Alegre, Rio Grande do
      Sul, Brazil]
AB  - This article focuses on the magnitude of work-related deaths in Porto Alegre, the
      capital of Rio Grande do Sul State, Brazil. Death certificates were used to
      investigate 159 cases, or 18% of the 877 deaths from external causes in 1992.
      Some 31 cases were identified. The principal cause of death among these workers
      was homicide, with 58% of cases (15 from fire arms and 3 from knives), followed
      by traffic accidents, with 29% (5 motor vehicle collisions and 4 pedestrians run
      down by motor vehicles). Of these 31 deaths, 17 were workers from the formal
      labor market, of whom 11 did not fit into the regular reporting procedures for
      work-related accidents. The other 14 deaths were of workers from the informal
      labor market (7), individuals involved in illicit activities (6), and unknown
      (1), in which cases reporting as work-related accidents was also inappropriate.
      These data suggest negligence by the public sector in dealing with this issue and
      the fact that official statistics fail to reflect the reality of daily working
      conditions. The authors conclude that health surveillance requires other data
      collection mechanisms besides those used by the Social Welfare System, so as to
      include all actual risks related to work situations.

PMID- 10886940
TI  - [Repetition Strain Injury]
AB  - Muscular-skeletal disorders of the upper limbs resulting from work involving
      repetition strain (RSI) are now the most frequent work-related diseases in early
      or late industrialized countries. The author maintains that in addition to being
      work-related diseases, RSIs are symbolic illnesses revealing the contradictions
      and social pathogenesis of the new cycle of development and crisis in capitalist
      production. Discussing the social and historical dimensions of this process, the
      author insists that the low efficacy of technical interventions by labor
      engineering, ergonomics, and clinical medicine in the prevention, early and
      adequate diagnosis, and treatment of such post-modern illnesses and the
      difficulty in rehabilitating and reincorporating such workers reflect precisely a
      broader determination of health and illness, since the appropriation,
      incorporation, and use of technological innovations and the new forms of work
      management are defined according to the exclusive interests of capital. Thus, a
      growing contingent of young workers (mainly females) from different labor
      categories are losing or under threat of losing their health and work capacity,
      two essential and closely linked public values. The solution to the SRI issue
      must be political and collective.

PMID- 10886941
TI  - [Mental health and automation: remarks on a case study in the railroad industry]
AB  - This article focuses on some relations between mental health and current
      technical, organganizaizational, and contextual changes in work. The paper
      presents some features of a case study, examining the impacts of the work
      situation in a railroad company on traffic controllers and conductors of a
      computorized, automatedded system. The article also discusses the implications
      for the safety of the system as a whole, including passengers.

PMID- 10886942
TI  - [Health and work in rural areas: sugar cane plantation workers in Ribeirao Preto,
      Sao Paulo, Brazil]
AB  - This study is based on an understanding of health and rural labor as a social
      process related to the characteristics of the agrarian issue in Brazilian
      society, focusing on sugar cane cutters in northeastern Sao Paulo State, Brazil,
      and attempting to identify patterns of attrition and reproduction in such labor.
      Based on direct observations, interviews with laborers and other agents involved
      in production, and a related bibliographical review, the analysis points to daily
      exposure of cane cutters to physical, chemical, and biological hazards resulting
      in various diseases, traumas, and accidents: dermatitis, conjunctivitis,
      dehydration, cramps, dyspnea, respiratory infections, high blood pressure, and
      wounds, besides aggravating the biopsychic burden underlying attrition patterns
      showing up in the spinal column, chest, head, and lumbar pains, nervous
      breakdowns, and other kinds of psychosomatic manifestations. This study of the
      work process pointed up its unhealthy working conditions and helped provide an
      overview of the conditions and means by which capital asserts itself in Brazil -
      in its self-reproduction process - especially in the agro-industrial sector.

PMID- 10886943
TI  - [Work and health in the Mexican "maquiladora" industry: a dominant trend in
      dominated neoliberalism]
AB  - This paper discusses health and working conditions of workers in the export
      oriented "maquiladora" industry in Mexico. The work is intensive and performed
      mostly by women. It is the country's second largest source of foreign exchange.
      The "maquiladora" industry illustrates the effect of neoliberalism on working and
      health conditions, unveiling the impact of overall flexibilization of labor and
      growing technological changes. The situation for risks and demands is complex.
      Taylorist demands persist in work organization, with multiple chemical risks and
      probable effects beyond the workplace. There are also demands from repetition
      strain and uncomfortable positions. Effects on workers' health include high
      morbidity rates as reflected by demands on the social health/welfare services,
      some two to four times greater than for other industrial workers. There is a high
      percentage of stress-related illnesses as the reason for medical consultation.
      There are also effects on workers' families. Low birthweight is 2.8 times higher
      in women who work in the "maquila" than in other labor groups. Work-related
      accidents are common, the second most frequent cause for medical consultation in
      some cases. The analysis identifies some of the tendencies in which workers'
      health could be important in coming years for large contingents of workers.

PMID- 10886944
TI  - [Child and adolescent workers: a commitment for collective health]
AB  - This paper presents some issues pertaining to child and adolescent labor and
      their impact on health, pointing out the main structural characteristics which
      are responsible for and socially justify the early incorporation of this segment
      into the labor market. In Brazil, legislation governing adolescent labor is
      frequently ignored, showing the need to implement health surveillance programs
      involving both public institutions and civil rights movements.

PMID- 10886945
TI  - [A proposal for worker's health surveillance with a gender perspective]
AB  - This paper deals with differences and inequalities. The current workers' health
      surveillance model is discussed, pointing to the need for a gender perspective in
      this area. The article maintains that certain classical notions should be
      reviewed and that risk maps can be more useful if they are capable of identifying
      exposure according to gender, thus enhancing the different kinds of division of
      labor under which they operate. Women workers' proposals are placed alongside
      sociological analyses in terms of the interface between production and
      reproduction and the debate over the gender perspective in the health-disease
      process. The paper concludes with an attempt to establish a new approach to
      workers' health surveillance, highlighting the centralness of work and the inter
      subjectiveness of determining the relationship between production and health.

PMID- 10886946
TI  - Organ Preservation in Patients with Head and Neck Cancer.
AB  - Approximately 40,000 cases of head and neck cancer occur annually in the United
      States. Most patients with advanced tumors have traditionally been treated with
      surgery and radiation. Chemotherapy and radiation are capable of controlling
      local tumors in selected laryngeal cancers, with preservation of laryngeal
      function, but with no improvement in survival. Studies are ongoing to optimize
      management. Patients considered for organ preservation using multimodality
      therapy should be motivated and compliant and have a good performance status.
      Optimal patient selection, multimodal treatment delivery, and follow-up require a
      well-coordinated team of specialists.

PMID- 10886947
TI  - Infectious and Inflammatory Diseases Masquerading as Head and Neck Malignancy.
AB  - Lesions of the head and neck and upper respiratory tract can be quite difficult
      to diagnose at times when presenting symptoms and signs appear out of character
      or biopsy of affected tissue reveals nonspecific results. A heightened awareness
      of important historical facts such as place of birth and residence, travel and
      occupation may provide important clues to narrow the differential diagnosis. Not
      all destructive ulcers and tumors of the head and neck are malignant.
      Inflammatory and infectious diseases that mimic cancer are presented.

PMID- 10886948
TI  - Perspectives on Chemotherapy of Head and Neck Cancer.
AB  - Conventional chemotherapy in head and neck cancer is confined to advanced
      recurrent disease not amenable to surgery or irradiation. The last decade has
      seen the development of combination chemotherapy programs resulting in improved
      response rates and the achievement of more complete clinical remissions, although
      overall survival has not been extended. These same treatments have demonstrated
      higher regression rates in untreated patients and a survival benefit for the
      complete responders to induction or neoadjuvant therapy. Neoadjuvant treatment
      appears to have an important role in laryngeal preservation resulting in improved
      quality of life. For patients with unresectable cancers of the head and neck,
      concomitant chemotherapy and radiation gives some survival advantage, albeit with
      an increase in toxicity. The incidence of these neoplasms may be capable of being
      decreased with biologic modifiers in some high-risk populations.

PMID- 10886949
TI  - A Model for Psychosocial Care in Head and Neck Cancer Patients.
AB  - Among cancer patients, those with disease of the head and neck area carry the
      highest psychiatric morbidity. Over 50% may be depressed even before treatment.
      Recognition and care of these problems is best done on a multidisciplinary basis
      with psychosocial care coordinated by a social worker. The concept of quality of
      life, a relatively new concept for head and neck cancer, may become an important
      tool to assist patients with initial decisions about care and to better define
      the success of management. In this paper we will review the psychiatric,
      behavioral and psychosocial problems related to the patient with
      otolaryngological cancer, discuss interventions to reduce patient and family
      distress, and describe a model for identifying those patients who need more
      intensive psychosocial care.

PMID- 10886950
TI  - Nurses and the Head and Neck Cancer Team.
AB  - Patients with head & neck cancer present particularly difficult problems in
      management, support, rehabilitation, and follow-up. Optimal care is best provided
      by a multidisciplinary team with very diverse capabilities that can address the
      multiple and changing needs of the patient and the family during the extended and
      complicated process of diagnosis, evaluation, care, rehabilitation, and follow
      up. The multidisciplinary team is headed administratively by a physician leader
      so that both policy and individual treatment decisions will be followed.
      Coordination of the team activities, as well as monitoring the progress of
      individual patients can be performed well by an educated and experienced nurse
      leader, with additional input from other nurses as required. Such a policy
      provides tangible benefit to patients, physicians, and institutions. The roles
      for and the benefits from such nursing leadership are described.

PMID- 10886951
TI  - Cancer and Health Care Reform - Potential Pitfalls.

PMID- 10886952
TI  - Diagnostic Liver Imaging with CT During Arterial Portography Enhancement.

PMID- 10886953
TI  - Pharmacokinetic Dosing of Carboplatin.

PMID- 10886954
TI  - Adoptive Immunotherapy: The Magic Bullet of Cancer Therapy?

PMID- 10886955
TI  - Do We Need Geriatric Oncology?

PMID- 10886956
TI  - A Gerontologist's Perspective on Cancer Biology and Treatment.
AB  - Cancer is largely a disease of older people, and mortality in the United States
      is increasing. Change in immune surveillance is not the only explanation for
      these phenomena. Time and specific age-related changes in tissues are other
      important factors. Some tumors in the elderly are biologically less aggressive in
      both animal tumor models and in humans. The need for more organized laboratory
      and clinical evaluation of the causes and effects of cancer in the aged is now
      being recognized.

PMID- 10886957
TI  - Clinical Course of Cancer in the Elderly.
AB  - Age is the single greatest risk factor for cancer. More people living longer
      means a dramatic increase in the number of older patients with cancer. Because
      older patients are likely to have several chronic diseases, cancer may be just
      one disease to consider in a given patient, or it may be the "straw that breaks
      the camel's back." Beyond these obvious facts is the possibility that cancer in
      the elderly may be somehow different from cancer in those who are younger. To
      examine this possibility, one can evaluate cancer incidence, presentation,
      treatment and survival. Breast cancer provides an excellent illustration of some
      of these parameters.

PMID- 10886958
TI  - Unique Characteristics of the Older Patient.
AB  - The study of older persons is filled with challenges. The rapid growth in their
      numbers as well as pressures to be accountable for the effectiveness and
      efficiency of medical care demand that we systematically devote energy and
      resources to the study of older persons. Increasing methodologic sophistication
      makes it no longer acceptable to generalize findings from younger populations to
      older ones. Furthermore, our understanding of aging and the implications of
      subject heterogeneity on study design and conduct make relevant studies now
      possible.

PMID- 10886959
TI  - Comprehensive Geriatric Assessment: Diagnostic, Therapeutic, and Prognostic
      Value.
AB  - Statistics on the geriatric population usually pertain to individuals aged 65
      years and older. Chronological age, however, especially between ages 65 to 79
      years, is a rather crude measure of physiologic aging, with some individuals
      still being vigorous, active, and independent and others experiencing great
      physical and psychosocial losses. As a specialty, geriatric medicine best
      addresses the needs of the latter group of persons, frequently referred to as the
      "frail elderly." The frail elderly are able to maintain their homeostasis in a
      nonstressed environment but have a strong inclination to decompensate when faxed
      with stressors which would not have been as taxing at a younger age. This
      propensity is due to more limited and easily exhaustible physiologic reserves.

PMID- 10886960
TI  - A Practical Approach to the Screening of Asymptomatic Older Persons for Cancer.
AB  - Secondary prevention of cancer is aimed at the individual in whom the disease has
      begun but symptoms have not yet appeared, in order to diagnose and treat early
      disease and/or prevent spread. Secondary prevention is a reasonable strategy for
      cancer control in the aged in whom primary prevention, aimed at the individual
      who has not yet developed the disease, may no longer be feasible. Screening the
      asymptomatic population at risk may be justified if it enables diagnosis at an
      asymptomatic or preclinical phase and if treatment at this stage leads to a
      longer life or reduced morbidity for those individuals whose disease is thereby
      detected.

PMID- 10886961
TI  - Management of Cancer in the Older Aged Person.
AB  - The management of cancer in the older person is an increasingly common aspect of
      oncologic practice. The central questions concern effectiveness and safety of
      antineoplastic therapy, clinical criteria to identify patients who may benefit
      from treatment, and individualized management plans. To address these questions,
      we review the influence of age on various forms of cancer treatment, explore the
      basis of treatment-related decisions in older persons with cancer, and propose
      areas for future investigation. Age itself is not a contraindication to cancer
      treatment. Individualized treatment plans, based on appropriate diagnosis,
      staging and comprehensive geriatric assessment, are most beneficial to the older
      patients.

PMID- 10886962
TI  - Cancer Chemotherapy - The Treatment Frontier of Medicine.

PMID- 10886963
TI  - Magnetic Resonance Image of the Thorax.

PMID- 10886964
TI  - Selected Aspects of Phenytoin Therapy in Oncology Practice.

PMID- 10886965
TI  - The Role of Fine Needle Aspiration Biopsy in Gynecologic Oncology.

PMID- 10886967
TI  - Hematopoietic Stem Cells for Transplantation: Marrow or Peripheral Blood?

PMID- 10886966
TI  - Cancer Patients with Lesions of the Hands: Is It Metastasis or an Infection?

PMID- 10886968
TI  - Syngeneic/Autologous Graft-vs-Host Disease: Mobilization of Autoimmune Mechanisms
      as Antitumor Immunotherapy.
AB  - Autologous bone marrow transplantation (BMT) is a therapeutic option for the
      treatment of neoplastic disease. The rate of tumor recurrence after autologous
      BMT remains unacceptably high and is presumably due to the absence of the
      antitumor effect of graft-vs-host disease (GVHD). Recent studies indicate that
      administration of the immunosuppressive drug cyclosporine (CsA) after
      syngeneic/autologous BMT elicits an autoimmune syndrome with pathology virtually
      identical to GVHD. This syndrome, termed syngeneic/autologous GVHD, can be
      induced in humans and rodent models and is associated with the development of
      cytolytic autoreactive T cells that recognize MHC class II determinants. Current
      studies in the rat model and preliminary clinical trials suggest that
      syngeneic/autologous GVHD provides a significant antitumor effect. This antitumor
      effect can be enhanced by the administration of either (-interferon, which
      upregulates the antigen recognized by the autoreactive effector cells, or IL-2,
      which amplifies the effector mechanisms of syngeneic/autologous GVHD.
      Mobilization of autoimmune mechanisms that mediate syngeneic/autologous GVHD may
      be a promising immunotherapeutic approach for certain human neoplastic diseases.

PMID- 10886969
TI  - A Rational Appraisal of Bone Marrow Transplantation and Immunosuppressive Therapy
      for Severe Aplastic Anemia.
AB  - With significant improvements in the rates of graft rejection and acute graft-vs
      host disease, bone marrow transplantation remains the therapy of choice for the
      young aplastic anemia patient with an HLA-matched related donor. While
      immunosuppressive therapy can induce responses in a significant proportion of
      patients, long-term follow-up studies have demonstrated a high rate of relapses
      and evolution to malignant clonal hematopoietic disorders. Therefore, this
      therapeutic option should be considered for patients who are not transplant
      candidates. The potential roles for hematopoietic growth factors and alternative
      marrow donors needs to be further defined.

PMID- 10886970
TI  - High-dose Chemotherapy and the Treatment of Metastatic Breast Cancer: Selecting
      the Regimen and the Source of Stem Cells.
AB  - High-dose chemotherapy followed by autologous stem cell rescue has been
      associated with an increased overall response rate and improved progression-free
      survival for patients with metastatic breast cancer when compared retrospectively
      to standard therapy. The optimal source of stem cells - peripheral blood or
      autologous bone marrow - has not been determined. We present results from two
      high-dose regimens - ifosfamide, carboplatin, and etoposide (ICE) or mitoxantrone
      and thiotepa (MITT) followed by autologous stem cell rescue - and analyze the
      outcomes for patients based on the regimen used and the source of stem cells.
      Disease responsiveness at the time of high-dose therapy is the most important
      factor for determining outcome. The source of stem cells did not affect
      progression-free survival for either group.

PMID- 10886971
TI  - Autotransplantation for Chronic Myelogenous Leukemia.
AB  - Alternate treatment strategies in the management of chronic myelogenous leukemia
      (CML) are essential if we are to impact on the ultimately fatal outcome for the
      majority of patients with this disease who are presently ineligible for
      allogeneic or syngeneic bone marrow transplantation. One such strategy is that of
      autologous stem cell rescue after high-dose therapy. Two essential aspects for
      success of this approach are the eradication of residual disease in the patient
      by myeloablative therapy and the eradication of disease in the collected stem
      cell product which is reinfused for restoration of hematopoiesis.

PMID- 10886972
TI  - Blood and Bone Marrow Hematopoietic Stem Cells for Transplantation: A Comparative
      Review.
AB  - Classical bone marrow transplantation collects bone marrow from a normal
      individual. This is infused into a patient rendered aplastic by high-dose
      chemoradiotherapy. Shortcomings include a limited donor pool and morbidity and
      mortality from graft-vs-host and graft rejection phenomena. Autologous marrow
      transplantation, in which the marrow of the patient to be transplanted is
      harvested, cryopreserved, and stored until needed, is not so constrained.
      Although marrow cannot be collected from some individuals due to hypocellularity,
      fibrosis, or infiltration with malignant disease, the presence of peripheral
      blood stem cells in the circulation allows these individuals to be treated with
      autologous transplantation therapy. It has been postulated that these
      hematopoietic progenitors have advantages over bone marrow collected stem cells,
      including safer and less expensive collections and accelerated rates of
      hematopoietic recovery following high-dose therapy and stem cell reinfusion.

PMID- 10886973
TI  - Clinical Practice Guidelines - Future Impact and Concerns.

PMID- 10886974
TI  - Percutaneous Needle Biopsy of the Adrenal Mass.

PMID- 10886975
TI  - Hepatic Veno-Occlusive Disease: A Role for Tissue Plasminogen Activator?
AB  - There are five published case reports of bone marrow transplantation (BMT)
      patients with hepatic veno-occlusive disease (VOD) who were treated with
      recombinant tissue plasminogen activator (rt-PA) and low-dose heparin. Two of the
      five patients had an initial response to rt-PA. One had complete resolution of
      clinical signs and symptoms. Bleeding occurred in three of the five. In a
      prospective, uncontrolled pilot study of seven allogeneic BMT patients, rt-PA was
      administered intravenously for two consecutive days, followed by low-dose heparin
      therapy. Five of the seven patients had a reduction in total bilirubin, and three
      of the five resolved their signs and symptoms of VOD. Adverse effects observed
      were limited to localized bleeding.

PMID- 10886976
TI  - Adoptive Immunotherapy and Interleukin-2 Following High-dose Therapy: A Potential
      Approach to Reduce Residual Tumor Cells.
AB  - Immune modulation and adoptive immunotherapy are being investigated as an
      additional cancer treatment modality. The influence of immunologic reactions,
      manifested as graft-vs-host disease (GVHD), has clearly been demonstrated in
      patients undergoing allogeneic bone marrow transplantation. More recently,
      adoptive immunotherapy by infusion of donor peripheral blood leukocyte products
      to recipients at relapse has shown benefit. As the immune system regenerates
      after high-dose therapy and stem cell transplantation, it is possible that we may
      be able to enhance an immune response against tumor cells. Trials are underway to
      evaluate the effect of interleukin-2 (IL-2) given early after transplantation to
      produce this effect.

PMID- 10886977
TI  - Prevention of Infection in Patients Undergoing Ablative Chemotherapy and Bone
      Marrow or Peripheral Blood Stem Cell Transplantation.

PMID- 10886978
TI  - Special Report: Lung Cancer Study Group - Final Analysis.

PMID- 10886979
TI  - Special Report: Ovarian Cancer Consensus Statement.

PMID- 10886980
TI  - Breast Cancer and the Older Woman: The Challenging Blend of Biology and Culture.

PMID- 10886981
TI  - Care Received by Older Women Diagnosed With Breast Cancer.
AB  - The influence on nonmedical factors in the presentation and the treatment of
      breast cancer may increase with the age of the patient. Using the New Mexico
      Tumor Registry data from 1968 to 1984, we found that the cancer was more advanced
      at presentation in women over age 65 years and that the stage of cancer was
      related to the availability of social support (married vs living alone). The
      relative risk of not receiving definitive cancer treatment increased with age up
      to 56.8% for women aged 85 years and over. Parameters which influenced the
      administration of definitive treatment were advanced age, access to
      transportation and cognitive status. Similar findings were obtained in overviews
      of Surveillance, Epidemiology, and End Results (SEER) data and hospital practices
      in Rhode Island and selected areas of California. Treatment of older patients
      with breast cancer is influenced by factors other than medical conditions. Better
      understanding of these factors may lead to improved outcome of cancer in older
      persons.

PMID- 10886982
TI  - Secondary Prevention of Breast Cancer in the Older Woman: Issues Related to
      Screening.
AB  - With advancing age, the prevalence of breast cancer and consequently the positive
      predictive value of screening tests increase. However, limited life expectancy
      may reduce the benefit of cancer screening. The integration of serial
      mammography, yearly or every two years, with yearly physical examination of the
      breast, reduces the breast cancer related mortality among women aged 50 to 70
      years and may be beneficial for older women. Of all age-related barriers to
      screening, the lack of physician support has been the most significant. A
      reversal in this trend was witnessed by a recent increase in mammography use by
      women aged 69 to 75 years. On the basis of existing data, it is reasonable to
      recommend screening for women up to age 75 years and for older women whose life
      expectancy is estimated at three years or longer.

PMID- 10886983
TI  - International Variations and Trends in the Incidence of Breast Cancer in Older
      Women.
AB  - This article explores age-related variations in breast cancer mortality in the
      western world and analyzes potential risk factors for older women. The highest
      breast cancer mortality rates are observed in England, Wales, and Denmark; the
      United States, Canada, Sweden, central and southern Europe have intermediate
      mortality rates; and Latin America and Russia have the lowest rates. Three case
      control studies involving over 4000 Italian women demonstrate that age at
      menarche is a risk factor only for premenopausal women; multiparity (>5 births)
      increases the risk of breast cancer for women under age 35 years but reduces the
      risk of breast cancer for older women. Obesity is a risk factor only for
      postmenopausal women, and the influence of other risk factors, such as age at
      first birth, family history and late menopause, does not show age-related
      variations. The influence of diet and steroidal contraceptives on the breast
      cancer rate in older women is not established.

PMID- 10886984
TI  - Geographic and Hospital Variation in the Management of Older Women With Breast
      Cancer.
AB  - Geographic and hospital characteristics function as predictors of the treatment
      of older women with breast cancer in the United States. Women are more likely to
      receive breast-conserving treatment if treated in the New England or mid Atlantic
      states. This treatment also is more widely used if women are treated in urban
      rather than rural areas, in teaching rather than nonteaching hospitals, in larger
      hospitals, in hospitals with radiation or geriatric services, or if treated by a
      surgeon who performs a higher volume of breast cancer surgeries. Breast cancer
      treatments vary substantially according to nonclinical factors.

PMID- 10886985
TI  - Management of Primary Breast Cancer in Older Patients: Treatment Options.
AB  - Age-related differences occur in the biology of breast cancer. Elderly patients
      have breast cancers that are more likely to be well differentiated, to have
      slower growth rates, and to be endocrine responsive. In elderly patients, primary
      breast cancers can frequently be treated by breast conserving surgery. Radiation
      therapy may be necessary less often after breast conserving surgery, and there is
      less rationale for prophylactic axillary dissection. Since elderly patients have
      been systematically excluded from randomized clinical trials, our data on breast
      cancer management has a less firm scientific basis than for younger patients. The
      available data suggest age should be only one consideration in selection of
      treatment, and to determine optimum therapy, age should not be a criterion to
      exclude patients from trials.

PMID- 10886986
TI  - Outpatient Treatment of Clinically Node-negative Breast Cancer in Elderly Women.
AB  - Successful management of elderly women with breast cancer presents a wide range
      of issues and challenges. The Istituto Nazionale per lo Studio e la Curo dei
      Tumori of Milan has performed a series of studies of women over age 70 years with
      clinically localized breast cancer which confirms the safety and effectiveness of
      wide local excision without lymph node dissection on an outpatient basis and
      under local anesthesia when axillary nodes are not palpable. Size and biologic
      characteristics such as hormone receptor status and proliferative activity have
      been used to determine the extent of effect of additional treatment with breast
      irradiation and tamoxifen on disease-free survival and actual survival. Factors
      affecting compliance to treatment protocols are being assessed.

PMID- 10886987
TI  - Breast Cancer in the Older Woman: Therapeutic Controversies.
AB  - This article reviews several controversial issues related to treatment of in
      situ, localized, locally advanced, and metastatic breast cancer in the elderly.
      In particular we examine the management of both ductal and lobular carcinoma in
      situ, the benefits of breast preservation, the indications for postoperative
      irradiation following partial mastectomy, the role of axillary lymphadenectomy in
      patients with a clinically normal axilla, and the value of systemic treatment for
      localized breast cancer. In addition, we review the indications for and duration
      of adjuvant hormonal treatment with tamoxifen and adjuvant cytotoxic
      chemotherapy, neoadjuvant systemic therapy for locally advanced breast cancer,
      and approaches to the palliation of metastatic disease.

PMID- 10886988
TI  - Long-term Tamoxifen Therapy for the Treatment of Breast Cancer.
AB  - Tamoxifen is a nonsteroidal antiestrogen that has become the frontline endocrine
      therapy for all stages of breast cancer. The drug is the only single-agent
      therapy that, when used in an adjuvant fashion, produces a survival advantage in
      postmenopausal women. Survival is longer when the estrogen receptor content of
      the primary tumor is higher, although receptor-poor patients still have a
      survival advantage from adjuvant tamoxifen equivalent to that noted with
      combination chemotherapy. The added advantages of tamoxifen are a maintenance of
      bone density and a decrease in fatal myocardial infarction. Although side effects
      from tamoxifen are few, patients must be examined for preexisting endometrial
      carcinoma before beginning drug use. Tamoxifen does not prevent the growth of
      endometrial tumors. Spotting and vaginal bleeding in postmenopausal patients
      taking tamoxifen should be followed up with a thorough gynecological examination.
      The incidence rate of endometrial cancer for tamoxifen-treated patients is 2 per
      1000 patients per year. More than 80% of detected endometrial tumors are stage 1
      disease and can be cured by hysterectomy.

PMID- 10886989
TI  - Psychological Adjustment to Breast Cancer by Older Women.
AB  - Older women (over aged 63 years) surveyed six months after their breast cancer
      diagnosis showed the same level of psychological adjustment as younger women.
      Within the sample of older women, psychological distress was positively
      correlated with amount of life-stressors (eg, financial, family, or health
      problems) experienced during the year prior to diagnosis. It is hypothesized that
      life development stage may be a better predictor of adjustment to breast cancer
      than chronological age.

PMID- 10886991
TI  - Cost Considerations for Elderly Women With Breast Cancer.

PMID- 10886990
TI  - Breast Cancer in Older Women: Quality-of-Life Considerations.
AB  - Breast cancer is the most common cancer in older women. This paper reviews
      various approaches to the measurement of quality of life, the important quality
      of life issues in the treatment of breast cancer, and what is known about the
      quality of life of older women with breast cancer. A number of studies suggest
      that older women adjust to breast cancer better than younger women and that they
      tolerate therapy as well as younger women. Ongoing and future research using
      newer approaches to quality-of-life assessment should provide additional
      information on this important topic.

PMID- 10886992
TI  - Magnetic Resonance Imaging.

PMID- 10886994
TI  - Role of Cytopathology in the Management of Breast Cancer.

PMID- 10886993
TI  - Cardiotoxicity Secondary to Cancer Treatment.

PMID- 10886995
TI  - Hemorrhagic Cystitis in Bone Marrow Transplant Patients: Is It an Infection or
      Chemotherapy Toxicity?

PMID- 10886997
TI  - Welcome to Joe's Place.

PMID- 10886996
TI  - Lung Cancer: Time for an End to Nihilism.

PMID- 10886998
TI  - Tobacco Use in Florida: Consequences and Costs.
AB  - The United States Surgeon General published the first report on the health
      effects of smoking in 1964. Thirty years later, the consequences and costs of
      tobacco use are known in much more detail. More than 400,000 Americans including
      28,000 Floridians, die prematurely each year from tobacco use. The 1993 total
      annual national smoking-attributable costs for health care services is $50.0
      billion, including $1.4 billion for Floridians. Approximately 20% of the smoking
      attributable health care costs in Florida are incurred by Medicaid patients.

PMID- 10886999
TI  - Lung Cancer: Diagnostic Techniques.
AB  - The diagnosis of lung cancer may be suspected on the basis of history, physical
      examination, or radiographic imaging studies. With rare exceptions, suspicions
      thus raised must be confirmed prior to the initiation of therapy. Advances in
      radiographic imaging provide an improved "roadmap" for designing diagnostic
      efforts. Advances in diagnostic procedures allow an easier, better tolerated, and
      more complete picture of the presence and extent of disease. A diagnostic
      algorithm using these advances provides the information necessary to design
      therapy while minimizing the cost, discomfort, and risk to the patient.

PMID- 10887000
TI  - Surgery for Stage III Non-Small Cell Lung Cancer.
AB  - The management of stage III non-small cell lung cancer has changed dramatically
      during the past ten years. Some stage IIIA tumors (T3, N0-1) are still treated
      primarily by surgical resection, but tumors with ipsilateral mediastinal nodal
      involvement (stage IIIA, N2) are now usually managed with induction chemotherapy
      or chemoradiotherapy, followed by surgical resection. Most stage IIIB (T4 or N3)
      tumors, previously treated with radiation alone, are now treated with combined
      radiation and chemotherapy. The treatment of patients with stage III non-small
      cell lung cancer continues to evolve, but the expanded use of combined modality
      therapy appears to have significantly improved the long-term survival of these
      patients.

PMID- 10887001
TI  - Role of Adjuvant Therapy in Patients With Surgically Resected Non-Small Cell Lung
      Cancer.
AB  - Strategies to eradicate micrometastatic disease in non-small cell lung cancer
      (NSCLC) with postoperative chemotherapy, radiation, or immunotherapy have been
      under investigation for almost three decades, yet to date, these studies have
      shown negative or mixed results. Recently accumulated evidence of survival
      benefit rendered by neoadjuvant chemotherapy added to definitive radiation and
      perhaps surgery, and the emergence of several new active agents have stimulated
      interest in reevaluation of adjuvant therapy in NSCLC. Routine use of adjuvant
      therapy, however, cannot be recommended until results of ongoing and planned
      clinical trials document its benefit.

PMID- 10887002
TI  - New Agents in Non-Small Cell Lung Cancer.
AB  - Lung cancer is the leading cause of death due to cancer in the United States in
      both men and women over the age of 35 years. Standard chemotherapy regimens have
      led to a modest impact on survival, but new strategies and more effective agents
      are needed, particularly those that interact favorably with radiation therapy.
      Recently, several agents with novel mechanisms of action - paclitaxel, docetaxel,
      topotecan, irinotecan, 9-aminocamptothecin, edatrexate, vinorelbine, and
      gemcitabine - have shown significant activity in patients with non-small cell
      lung cancer. The results of those clinical trials and the plans for further
      development are discussed.

PMID- 10887004
TI  - Clinical Trials - Who's Paying for Them?

PMID- 10887003
TI  - Limited Stage Small Cell Lung Cancer: Current Treatment and Clinical Trials.
AB  - Progress in the treatment of patients with small cell lung cancer (SCLC), which
      seemed so rapid a decade ago, appears to have slowed. This has led to frustration
      and discouragement. Some of this pessimism is based on premature optimism in the
      past, but much stems from the realization that over 90% of patients with limited
      stage SCLC still die of the disease. Such aggregate judgments obscure the facts
      that major advances have been made in understanding the biologic basis of this
      disease and that modest but clinically valuable progress has been made in
      therapy. In view of the large number of patients diagnosed with SCLC each year,
      relatively small improvement in long-term outcomes can result in the survival of
      many patients each year. This article reviews the current status of care for
      patients with limited stage SCLC and discusses directions for clinical research
      in the 1990s.

PMID- 10887005
TI  - Non-Hodgkin's Lymphoma of the Breast, Large-cell Type.

PMID- 10887007
TI  - Sepsis in the 1990s: The Management of Chaos.

PMID- 10887006
TI  - The Biology of Lung Cancer: An Overview.

PMID- 10887008
TI  - Diagnosis and Treatment of Soft Tissue Sarcomas.

PMID- 10887009
TI  - Pathology of Soft Tissue Sarcomas.
AB  - Approximately 5600 patients with soft tissue sarcomas are diagnosed annually in
      the United States. The pathologist must distinguish a diverse group of
      histiogenic types of soft tissue sarcomas from reactive processes, benign tumors,
      melanomas, lymphomas, and carcinomas. Sarcomas are difficult to grade, since the
      grading schemes tend to be subjective. However, newer techniques, including
      electron microscopy, immunohistochemistry, DNA flow cytometry, cytogenetics, and
      molecular biology, can improve diagnostic accuracy and provide information on the
      biologic potential of these tumors. Communication between the pathologist and the
      clinician helps the pathologist provide as much information as possible from
      sarcoma biopsy and resection specimens.

PMID- 10887010
TI  - Magnetic Resonance Imaging of Soft Tissue Tumors.
AB  - Magnetic resonance imaging (MRI) is the only noninvasive method of defining a
      soft tissue tumor. The anatomical extent of the tumor and the involvement of
      various adjacent tissues and structures can be determined. This information is
      invaluable for staging and optimal management of the disease.

PMID- 10887011
TI  - Surgical Management of Extremity Soft Tissue Sarcomas.
AB  - The surgical management of soft tissue sarcomas involves a complex
      multidisciplinary approach. Prior to any definitive procedure, a thorough
      assessment, including history, physical examination, staging studies, and
      appropriate biopsy technique, along with extensive preoperative planning, should
      be performed to ensure an accurate diagnosis and appropriate treatment. Adjuvant
      therapy has made limb salvage surgery possible. The techniques outlined here are
      demanding and should be carried out by experienced surgeons. The use of
      amputation and the incidence of local recurrence after limb salvage have
      declined, while survival and quality of life have improved. The importance of
      staging studies, appropriate biopsy technique, and preoperative planning are
      vital in maintaining the current level of success.

PMID- 10887012
TI  - The Role of Radiation in Patients With Soft Tissue Sarcomas.
AB  - Radiation is a critical component of the treatment strategy for limb salvage of
      patients with soft tissue sarcoma. In modest dose levels, eg, 60 to 66 Gy,
      radiation eradicates sarcoma cells in grossly normal tissue that abuts the
      evident sarcoma and deactivates the microscopic extensions of tumor into adjacent
      normal tissue. Furthermore, radiation alone at higher dose levels, eg 75 Gy, is
      effective in patients with small volumes of sarcoma. Clinical experience
      indicates that the tumor control probability following a specified dose protocol
      is approximately the same for both epithelial and mesenchymal tumors when they
      are stratified for tumor volume and clinical presentation and only infiltrative
      tumors are considered. This provides support for the further use of radiation for
      this group of patients.

PMID- 10887013
TI  - The Role of Chemotherapy in Soft Tissue Sarcomas.
AB  - The progress in management of localized soft tissue sarcomas in recent years has
      resulted in improved functional status and overall outcome, but advancement in
      metastatic disease has been less than impressive. Doxorubicin and dacarbazine
      based chemotherapy programs have resulted in response rates of up to 50% with a
      small but finite cure fraction, especially in conjunction with surgical resection
      of residual abnormalities. In the 1980s ifosfamide plus mesna was identified as
      an effective salvage regimen. Studies evaluating the role of ifosfamide as a
      frontline agent in combination with doxorubicin have reported increased
      toxicities without a significant additive or synergistic therapeutic benefit.
      High-dose chemotherapy for sarcomas is now feasible with the advent of growth
      factors and/or peripheral blood progenitor cell reinfusion for bone marrow
      support. While these approaches seem promising with improved complete and overall
      responses, survival benefit is yet to be seen.

PMID- 10887014
TI  - Rehabilitation of Patients Following Resection of Extremity Soft Tissue Sarcomas.
AB  - Patients with extremity soft tissue sarcomas present a challenge to the
      rehabilitation team. Most will require either an amputation or a local resection
      combined with radiation therapy, and both treatment modalities require extensive
      rehabilitation to achieve optimal results. Success depends on a multidisciplinary
      approach with communication among all members of the rehabilitation team, as well
      as well-fitted prosthetics and/or orthotics, physical therapy, occupational
      therapy, moral and emotional support, and encouragement. A realistic approach and
      a positive attitude throughout the treatment process help to motivate the patient
      to meet the demands of the rehabilitation program.

PMID- 10887015
TI  - British Cancer Care Today - Our Cancer Care of Tomorrow?

PMID- 10887016
TI  - Cavernous Hemangioma.

PMID- 10887017
TI  - Mifepristone (RU 486): Rationale and Use in Cancer Therapy.

PMID- 10887018
TI  - Acquired Immunodeficiency Syndrome-Related Non-Hodgkin Lymphoma.
AB  - Non-Hodgkin lymphoma affects 5% to 10% of patients with acquired immunodeficiency
      syndrome (AIDS) in the United States. Usually of B-cell or indeterminate
      phenotype and high-grade histology, the disease shows a predilection to involve
      extranodal sites such as the bone marrow and the central nervous system. The
      pathogenesis involves chronic antigen stimulation producing B-cell hyperplasia in
      a setting of progressive immunologic deterioration. Treatment is not standardized
      and is tailored to the patient's immune function and clinical status. New
      approaches, validated by clinical trials, are needed.

PMID- 10887019
TI  - Hematological Effects of Human Immunodeficiency Virus Infection.
AB  - Anemia, thrombocytopenia, and neutropenia are common manifestations in patients
      with human immunodeficiency virus infection that become more frequent and severe
      with progression from the asymptomatic state to acquired immunodeficiency
      syndrome (AIDS). Causes of anemia in AIDS include nutritional deficiencies,
      infection, and marrow suppression by antiretroviral drugs and by the disease
      itself. Autoimmune hemolysis and blood loss from gastrointestinal lymphoma or
      Kaposi sarcoma may also contribute. Granulocytopenia may be due to infection,
      autoimmunity, or bone marrow suppression by drugs or the immunodeficiency virus.
      Lymphopenia, the classic hallmark of the disease, typically affects T-helper
      cells first and worsens as the disease advances. Lymphopenia is a result of the
      direct cytopathic effects of the virus. Thrombocytopenia can occur from
      antibodies causing an idiopathic thrombocytopenic purpura-like state from bone
      marrow suppression or from thrombotic thrombocytopenic purpura. A prolonged
      partial thromboplastin time due to a coagulopathy caused by lupus anticoagulant
      causing has been described. A variety of malignancies occurs.

PMID- 10887020
TI  - Patterns of Breast Cancer Treatment: A Comparison of a Rural Population With an
      Urban Population and a Community Clinical Oncology Program Sample.
AB  - This Illinois study shows that rural patients who were postmenopausal and node
      negative were more likely than urban patients to have a modified radical
      mastectomy (P=.03) and less likely to have had an oncology consultation (P=.01).
      Postmenopausal rural patients with positive nodes were more likely than
      comparable CCOP patients to receive radiation therapy (P=.0001), regardless of
      surgical choice, and were less likely to get hormone therapy than urban patients
      with an estrogen receptor-positive tumor (P=.007). After adjustment for
      confounders, rural patients were less likely than those in either comparison
      group to have limited surgery (odds ratio [OR] = 2.8, 95% confidence interval
      [CI] 1.4, 5.6 for urban patients, and OR = 2.9, 95% CI 1.5, 5.7 for CCOP
      patients) and more likely than CCOP patients to undergo radiation (OR = 0.2, 95%
      CI 0.1, 0.4). These data can be used to assess the impact that dissemination of
      state-of-the-art treatment strategies has on breast cancer mortality.

PMID- 10887021
TI  - Gene Therapy: A New Approach for Treatment of Cancer.
AB  - The identification of critical genes that encode for regulatory proteins has
      helped elucidate the molecular mechanisms that govern cell proliferation and
      malignant transformation. Several approaches to gene therapy for cancer have been
      described. These include the use of fibroblasts expressing suicide genes,
      restoration of expression of tumor suppressor genes, cytokine gene therapy,
      genetic modification of T lymphocytes, and protection of normal hemopoiesis in
      cancer patients. Clinical trials are underway in all these areas.

PMID- 10887022
TI  - Diagnosis and Management of Thyroid Cancer.
AB  - Thyroid carcinoma, which comprises the majority of endocrine malignancies, has a
      substantial annual morbidity and mortality based on age and other predisposing
      factors. Diagnosis of a growing thyroid nodule can be difficult, but
      ultrasonography, radionuclide scanning, and fine needle aspiration allow the
      majority of nodules to be properly characterized. Treatment of differentiated
      thyroid carcinoma remains controversial. Surgical resection continues to be the
      most important modality with long survival if the tumor is resected early. Newer
      imaging techniques have improved the diagnosis of locally recurrent or metastatic
      disease. Radioactive iodine ablation is indicated for patients with "high-risk"
      tumors or advanced age. Few patients respond to cytotoxic chemotherapy. In the
      past decade, advances in the screening and diagnosis of medullary thyroid
      carcinoma have led to earlier detection with improvement in survival.

PMID- 10887023
TI  - Adapting Private Practice Medical Oncology to a Changing Health Care System.

PMID- 10887024
TI  - Aneurysm of the Hepatic Artery of the liver hilum.

PMID- 10887025
TI  - Fludarabine in Acute Leukemia.

PMID- 10887026
TI  - Techniques of Diagnostic Molecular Pathology.

PMID- 10887027
TI  - Eosinophilia: Its Significance in Neoplasia, Infectious Diseases, and Other
      Conditions.

PMID- 10887028
TI  - Breast Cancer and the American Woman - Past, Present, and Future.

PMID- 10887029
TI  - Breast Cancer Screening: Is It Worthwhile?
AB  - There is more evidence of the effectiveness of breast cancer screening with
      mammography than for any other cancer screening strategy. Yet breast cancer
      screening remains controversial. Important practical issues, such as when to
      start screening, when to stop screening, and how often to screen, remain
      controversial, and there are valid concerns about the cost-effectiveness of
      screening when compared to other health care choices. This article presents the
      foundations for the breast cancer screening recommendation and an overview of the
      debated issues surrounding this screening strategy.

PMID- 10887030
TI  - Breast Cancer Genetics: Relevance to Oncology Practice.
AB  - Our knowledge of genetic mechanisms involved in cancer initiation, promotion, and
      progression recently has expanded. In order to benefit from this expansion and to
      apply genetic discoveries to current protocols for prevention, screening,
      diagnosis, treatment, prognosis, and monitoring for minimal residual disease, a
      working knowledge must be developed of the genetic principles, oncogenes, tumor
      suppressor genes, and genetic models of carcinogenesis. Genetic susceptibility
      testing for cancer soon will be introduced into oncology practice through
      established familial risk counseling programs, and the oncologist must be
      prepared to address the medical, ethical, legal, economic, psychological, and
      social issues that accompany this testing.

PMID- 10887031
TI  - Today's Adjuvant Therapy in Breast Cancer: Who Should Receive What?
AB  - Breast cancer remains a major public health problem. Prospective randomized
      trials comparing therapies are essential to improve current therapy but, for
      those women unable or unwilling to participate in clinical trials, treatment
      plans are needed. Treatment recommendations can be based on available information
      from individual trials and from a large collaborative overview. This information
      will be reviewed with treatment recommendations presented for subpopulations of
      breast cancer patients.

PMID- 10887032
TI  - Dietary and Chemoprevention Strategies for Breast Cancer Prevention.
AB  - Breast cancer is the most common cancer among American women. Strategies to
      eliminate or cure invasive breast cancer (eg, treatment of established disease
      and early detection) have been joined by a promising new approach, prevention.
      Epidemiologic studies have yet to demonstrate that dietary modification can
      reduce the risk of breast cancer, but important trials are ongoing. The
      chemoprevention program of the National Cancer Institute (NCI) has been underway
      for a decade. The discovery of biomarkers, or "intermediate endpoints," that can
      serve as surrogates for the ultimate endpoint, breast cancer, is crucial to the
      success of this program. The chemoprevention programs of NCI and the Division of
      Cancer Prevention and Control have identified promising cancer prevention
      compounds, many of which are being studied in clinical trials.

PMID- 10887034
TI  - Pseudomyxoma peritonei.

PMID- 10887033
TI  - The Academic Medical Center - Will the Lion Wake Up?

PMID- 10887035
TI  - Chemotherapy-Induced Neurotoxicity.

PMID- 10887036
TI  - Fine Needle Aspiration Biopsy Cytology of Argyrophilic Carcinoma (Carcinoid
      Tumor) of the Breast.
AB  - Argyrophilic carcinoma of the breast, previously referred to as carcinoid tumor,
      is a rare form of ductal carcinoma that can be diagnosed by fine needle
      aspiration biopsy. This tumor is characterized by widespread cytoplasmic granules
      with affinity for reduced silver stains or argyrophilia. The tumor tends to occur
      in older women and behaves in a fashion similar to classic ductal carcinoma. The
      argyrophilia may reflect stored neurosecretory granules or, less frequently,
      mucinous or lactational changes. Carcinoid or other neuroendocrine syndromes are
      not observed.

PMID- 10887037
TI  - Diagnostic Molecular Pathology and Infectious Disease.

PMID- 10887038
TI  - Alzheimer's disease: transgenic mouse models and drug assessment.
AB  - Alzheimer's disease (AD), characterized by neuritic plaques and neurofibrillary
      tangles of the brain, is experienced by more and more elderly people in a form of
      senile dementia. Four genes are closely linked with AD and are located on
      chromosomes 21, 19, 14 and 1. Transgenic technology enables the development of
      animal models for research into this human disease. Recently reported transgenic
      AD mouse models, which express AD-related mutant human genes, develop some
      significant aspects of AD-like pathology. The specific role of these mice in
      representing different targets, the consequent pathology of AD and the
      availability of this increasingly popular tool for investigating new therapeutic
      strategies for AD are reviewed.

PMID- 10887039
TI  - The protective effect of glutathione administration on adriamycin-induced acute
      cardiac toxicity in rats.
AB  - Adriamycin (ADR) is a potent antitumor antibiotic drug known to cause severe
      cardiac toxicity. Although ADR generates free radicals, the role of these
      radicals in the development of cardiac toxicity is still not well understood. In
      the present study, we evaluated the effect of glutathione (GSH) supplementation
      or depletion on ADR-induced cardiotoxicity in male Wistar rats. Cardiac toxicity
      was induced by a single intraperitoneal injection of ADR (20 mg kg(-1)) and
      manifested by an increase in heart rate, blood pressure elevation, and increased
      serum creatine kinase (CK) and lactate dehydrogenase (LDH). The extent of
      lipoprotein oxidation, lipid peroxide measured as malondialdhye (MDA), total
      homocysteine (tHcy), lipid profile, and atherogenic index were markedly elevated,
      whereas cardiac GSH content was dramatically decreased in ADR rats. Pre- and co
      treatment of ADR rats with GSH (5 mm kg(-1)) (ADR +GSH) markedly reduced the
      levels of CK, LDH, lipoprotein oxidation susceptibility, cardiac MDA, tHcy and
      atherogenic index, and elevated GSH levels in cardiac tissues. In contrast, GSH
      depletion through administration of l-buthionine-(S,R)-sulfoximine (BSO) (15 mm
      kg(-1)) before and after ADR injection (ADR +BSO) greatly exacerbated ADR
      cardiotoxicity compared to the control and ADR groups. Finally, there were also
      severe cardiac histopathological changes in ADR and ADR +BSO groups, which were
      nearly restored by GSH treatment. These results suggest that GSH inhibits ADR
      cardiotoxicity and might serve as a novel combination with ADR to limit free
      radical-mediated organ injury.

PMID- 10887040
TI  - Direct inotropic effects of propofol and adenosine on rat atrial muscle: possible
      mechanisms.
AB  - Experiments were designed to evaluate the mechanisms of propofol and adenosine in
      rat atrial muscle. Atria were suspended in the isolated organ bath system for
      isometric tension recording and response to propofol and adenosine were tested in
      the absence and presence of glibenclamide, N(G)-nitro-arginine-methyl-ester (l
      NAME), tetraethylammonium (TEA) and 8-phenyltheophylline (8-PT). The inotropic
      effect of propofol was elicited by TEA and glibenclamide. In contrast, l-NAME and
      8-PT has no effect on the propofol-induced inhibition of atria. Furthermore,
      atria exhibited a diminished sensitivity to the adenosine-induced negative
      inotropic effect in the presence of the K(ATP)channel inhibitor glibenclamide,
      but not the non-specific K(+)channel inhibitor TEA. The adenosine A(1)receptor
      antagonist 8-PT decreased the responsiveness of adenosine-induced inhibition of
      atrial muscle. We propose that propofol-induced inotropy is generally mediated by
      K(+)channels, whereas adenosine-induced inotropy is partially mediated by
      K(+)channels. Both propofol- and adenosine-induced inotropy were not mediated by
      nitric oxide release. Our study provides further evidence that there was no
      contribution of adenosine in the propofol-induced inotropy.

PMID- 10887041
TI  - Hexarelin, a growth hormone secretagogue, protects the isolated rat heart from
      ventricular dysfunction produced by exposure to calcium-free medium.
AB  - The effect of hexarelin, a potent synthetic growth hormone (GH)-secretagogue, and
      of human GH were studied on the mechanical and metabolic changes elicited by the
      calcium-paradox phenomenon in isolated rat hearts submitted to 5 min Ca(2+)
      depletion followed by reperfusion with reintegrated Ca(2+)medium. Hexarelin, (80
      microg kg(-1)s.c.) administered to normal male young rats for 3 and 7-day, time
      dependently antagonized the sudden increase in resting tension of the isolated
      perfused hearts upon Ca(2+)-repletion. The beneficial effect of hexarelin was
      particularly evident in the 7-day treatment. In this instance, ventricular
      contraction peaked at 30 +/- 2 mmHg (controls, 76 +/- 7 mmHg) and the recovery of
      left ventricular developed pressure (LVDP) was two times higher (P<0.001) than
      that recorded in controls (LVDP, 29 +/- 2 mmHg). Moreover, the release of
      creatine kinase into the heart effluent during Ca(2+)-repletion was reduced by
      40% (P<0.001) as compared to controls. The protecting activity of hexarelin
      against the damage induced by calcium-paradox in the heart was apparently
      divorced from any stimulation of the GH/insulin-like growth factor (IGF) axis,
      since plasma and heart concentrations of IGF-1 were similar to those measured in
      control rats. In contrast to hexarelin, administration of GH (400 microg kg(-1)
      s.c.) for 7 days did not affect the mechanical and metabolic manifestations of
      calcium-paradox in the perfused rat hearts. Hexarelin (8 microg ml(-1)) perfused
      for 60 min through the hearts in recirculating conditions did not modify heart
      contractility and failed to prevent ventricular hypercontractility developed on
      Ca(2+)-readmission. In conclusion, the mode of action of hexarelin in protecting
      the rat heart from calcium-paradox events is presently unknown; it would seem,
      however, that only prolonged exposure to hexarelin makes myocardial cells
      competent to maintain cytoplasmatic electrolyte balance and to control of
      Ca(2+)gain, two functions that are impaired during the 'calcium-paradox'
      phenomenon.

PMID- 10887042
TI  - Antiplatelet and antithrombotic effect of D-003.
AB  - D-003 is a mixture of higher primary aliphatic saturated acids purified from
      sugar cane wax whose main component is octacosanoic acid followed by
      triacontanoic, dotriacontanoic, and tetratriacontanoic acids. The aim of this
      study was to evaluate the effects of D-003 on: ex vivo platelet aggregation,
      arterial thrombosis and bleeding time in rats. In addition, time course of
      antiplatelet effects of D-003 was also investigated on ex vivo platelet
      aggregation in guinea-pigs. D-003 (25-200 mg kg(-1)) orally administered at
      single or repeated doses (3 days) inhibited platelet aggregation induced by
      collagen (2.2 microg ml(-1)) and ADP (2 micromol l(-1)) in rats, and collagen
      (0.25 microg ml(-1)) induced aggregation in guinea-pigs in a dose-dependent
      manner. Single doses of D-003 (5-500 mg kg(-1)) administered orally 2 h before
      induction of arterial thrombosis significantly inhibited the reduction of rectal
      temperature. D-003 administered at a single dose (50-200 mg kg(-1)) 2 h before
      the experiment significantly increased the bleeding time in a dose-dependent
      manner. The time-course effects of D-003 on platelet aggregation, arterial
      thrombus formation, and bleeding time showed no effect 0.5 h after dosing, and
      maximal effects exhibited 1-2 h after treatment, whereas no significant effects
      were found 4 h after treatment.

PMID- 10887043
TI  - The impact of ofloxacin on rat testicular DNA: application of image analysis.
AB  - Ofloxacin induces its antibacterial action mainly by inhibition of DNA gyrase
      which is equivalent to topoisomerase II in mammalian cells. The present study was
      focused on the impact of ofloxacin on rat testicular DNA ploidy in a dose
      response relationship using an image analysis technique on testicular sections
      following Fuelgen DNA staining. Sperm count and motility as well as sperm head
      abnormality tests were also investigated. Ofloxacin was given p.o. in doses of
      36, 72 and 360 mg kg(-1) day(-1) for 15 consecutive days. The animals were then
      left to live safely to day 60 from starting the experiment to give them a chance
      to complete the cycle of spermatogenesis. Results revealed that ofloxacin
      significantly decreased the percentage of haploid cells in a dose-dependent
      manner with concomitant increase in the percentage of diploid cells. Sperm count
      and motility was also markedly decreased in a dose-dependent fashion. Sperm head
      abnormality showed no marked change following ofloxacin treatment. In conclusion,
      ofloxacin induced a marked disturbance in rat testicular DNA ploidy, which may be
      explained on the basis of cross-reactivity to topoisomerase II.

PMID- 10887044
TI  - Sequence-dependent toxicity profile in modified FAMTX (fluorouracil-adriamycin
      methotrexate) chemotherapy with lenograstim support for advanced gastric cancer:
      a feasibility study.
AB  - For advanced irresectible gastric cancer, sequential high-dose methotrexate and 5
      fluorouracil (both on day 1) combined with adriamycin on day 15 (FAMTX regimen),
      cycled every 28 days, is a fairly effective but toxic treatment, with a high
      incidence of neutropenic fever, dose reductions and dose delays. In order to
      improve FAMTX toxicity, we studied the feasibility of two modified FAMTX regimens
      with lenograstim support. Seven advanced gastric cancer patients were treated
      with all three FAMTX drugs on day 1 followed by lenograstim 150 microgm(-2)for 10
      days, in 21-day cycles (FUMA regimen). The next seven patients were treated with
      the same drugs at the same doses, but with adriamycin 1 day prior to methotrexate
      and 5-fluorouracil administration (AFUM regimen). Patients were monitored for
      toxicity, response, and survival. The total number of courses was 27 for FUMA and
      35 for AFUM with a median of four courses per patient in each cohort. In the FUMA
      regimen, considerable toxicity consisting of mucositis and fatigue as well as
      grade 4 neutropenia occurred, and forced four out of seven patients to stop
      treatment. The consecutive AFUM regimen showed only mild toxicity, and all
      patients could finish treatment without dose reductions or delays. We found
      unanticipated and probably sequence-dependent toxicity profiles in two
      investigational, modified FAMTX schedules with lenograstim support, leading to
      high rates of dose-limiting toxicity in the FUMA regimen as opposed to mild
      toxicity in the AFUM regimen, even though the same total drug doses and treatment
      cycle length (dose intensity) were employed.

PMID- 10887045
TI  - L -sulpiride, at antidepressant dosage, prevents conditioned-fear stress-induced
      gastric lesions in rats.
AB  - It has been previously shown that long-term treatment with low doses of l
      sulpiride is highly effective in rat models of depression and of anticipatory
      anxiety/panic behavior. The present study was aimed at investigating whether the
      same treatment can prevent the ulcerogenic effect of repeated inescapable
      stresses. In adult rats, the repeated (7 consecutive days) exposure to an
      uncontrollable stressful condition (inescapable 2.5 mA scrambled shock for 60 s)
      produced the development of gastric lesions (multiple punctiform telangiectasias
      in all rats, with superficial erosions or more severe ulcerations in 10 out 13
      rats; score 4.67 +/- 0.44). l-sulpiride, intraperitoneally injected once a day at
      an antidepressant dose level (4 mg kg(-1) per day), starting 21 days before the
      beginning of the 7-day sequence of inescapable punishments ( = 28 daily
      treatments), almost completely prevented the stress-induced gastric injury (score
      1.67 +/- 0.29; P< 0.001 vs saline-treated rats, Mann-Whitney U test). These
      results show that, in rats, a long-term treatment with low doses of l-sulpiride
      prevents the development of gastric lesions induced by chronic exposure to
      uncontrollable stress.

PMID- 10887046
TI  - Potency of Semecarpus anacardium Linn. nut milk extract against aflatoxin B(1)
      induced hepatocarcinogenesis: reflection on microsomal biotransformation enzymes.
AB  - The effect of Semecarpus anacardium Linn. nut milk extract on host detoxification
      system in aflatoxin B(1) induced hepatocellular carcinoma, which is a vital
      mechanism in cancer treatment, was studied in male albino rats. Oral
      administration of nut extract (200 mg kg(-1)body weight per day for 14 days) is
      found to be highly effective in inducing phase I and phase II biotransformation
      enzymes. The obtained results have shown an overall decrease of liver microsomal
      cytochrome P450, cytochrome b5, NADPH-cytochrome P450 reductase, NADH-cytochrome
      b5 reductase, and aniline hydroxylase with a subsequent decrease of phase II
      enzymes, glutathione-S-transferase and UDP-glucuronyl transferase in cancer
      bearing animals. The Semecarpus anacardium nut extract affords anticancer
      activity by enhancing both phase I and phase II enzymes to near normal levels. We
      propose that, much of the anticarcinogenic potency of Semecarpus anacardium nut
      extract on aflatoxin B(1)-induced hepatocarcinogenesis is mediated through the
      induction of hepatic biotransformation enzymes.

PMID- 10887047
TI  - Acceleration of body clearance of diethylCarbamazine by oral activated charcoal.
AB  - The effect of activated charcoal (AC) on body clearance of diethylcarbamazine
      (DEC) was investigated in six healthy volunteers. On three occasions at weekly
      intervals, each subject received 150 mg of DEC with 350 ml of water. One and two
      weeks later, 150 mg of DEC plus 7.5 g and 15 g of AC, respectively, in 350 ml of
      water as a charcoal slurry. The non-renal clearance of DEC expressed as the total
      body clearance of DEC was increased after treatment with AC. The 45.2, 79.6
      percent and 58.6, 81.6 percent reductions in maximum concentration and area under
      the concentration-time curve, respectively, suggest an appreciable adsorption of
      DEC by AC (7.5 and 15 g) in the gut. Serum eliminating half-life was decreased
      upon treatment with AC (7.5 and 15 g). These results indicate that AC accelerates
      the body clearance of DEC by increasing non-renal elimination of the drug.

PMID- 10887048
TI  - Decreased body temperature dependent appearance of behavioral despair in the
      forced swimming test in mice.
AB  - Effects of body temperature on the immobile response and brain glucose metabolism
      were examined in the forced swimming test in mice. The first experiment was
      performed to study behavior, after initial periods of vigorous activity, a
      characteristic immobile posture occurred when the water was 25 and 35 degrees C.
      However, several minutes after forced swimming at 25 degrees C, significantly
      decreased spontaneous motility occurred in a time-dependent manner, but no
      changes was observed at 35 degrees C. Our interpretation was that mechanisms of
      acquisition and retention of the forced swim-induced immobile response differed.
      Body temperature was also significantly decreased at 25 degrees C but not at 35
      degrees C in the forced swimming test. This lowering of body temperature almost
      paralleled the immobile response. The second experiment was a biochemical study
      in which the uptake of [(14)C] 2-deoxy-d-glucose into the brain significantly
      decreased after forced swimming at 25 degrees C but did not change in the forced
      swim loaded mice when the water was 35 degrees C. These results suggested two
      types of immobile mechanisms in the forced swimming test: (1) an early phase
      acquisition of the immobile response which might be related to adaptive response
      and (2) a late phase to retain the immobile response which might be related to
      the decrease in brain glucose metabolism.

PMID- 10887049
TI  - Linalool modifies the nicotinic receptor-ion channel kinetics at the mouse
      neuromuscular junction.
AB  - Linalool is a monoterpene compound reported to be a major component of essential
      oils in various aromatic species. Several linalool-producing species are used in
      traditional medical systems. Among these is Aeolanthus suaveolens G. Dom
      (Labiatae) which is used as an anticonvulsant in the Brazilian Amazon.
      Psychopharmacological in vivo evaluation of linalool showed that this compound
      has dose-dependent marked sedative effects at the central nervous system (CNS),
      including hypnotic, anticonvulsant and hypothermic properties. It has been
      suggested that these neurochemical effects might be ascribed to the local
      anaesthetic activity of linalool. The present study reports an inhibitory effect
      of linalool on the acetylcholine (ACh) release and on the channel open time in
      the mouse neuromuscular junction. These findings could provide a rational basis
      to confirm the traditional medical use of linalool-producing plant species.
      Indeed, our data demonstrate some interactions in the modulation of the ACh
      release at the mouse neuromuscular junction, which are well correlated with the
      suggested molecular mechanisms. Linalool induced a reduction of the ACh-evoked
      release. The possibility that this effect could be ascribed to some interaction
      with pre-synaptic function is noteworthy. Moreover, the inhibitory effect induced
      on the kinetics of the miniature end-plate current decay demonstrates a local
      anaesthetic action, either on the voltage or on the receptor-activated channels.

PMID- 10887050
TI  - Cyproterone acetate and reversal of the impaired endometrial decidualization in
      streptozotocin-diabetic pseudopregnant rats.
AB  - Reproductive dysfunction in the female diabetic rat is associated with impaired
      hypothalamic-hypophyseal system, anovulation, insufficiency of ovarian
      steroidogenesis and spontaneous failure of pregnancy. Formation of decidua, the
      highly modified endometrium of pregnancy and pseudopregnancy could only be
      achieved when the uterus was sensitized by a sequence of oestrogen and
      progesterone. In this study, we examined whether the impaired expression of
      endometrial decidualization in the pseudopregnant rat is linked with diabetes
      associated hypersecretion of testosterone. Rats were made pseudopregnant by
      sterile mating. Diabetes was induced by streptozotocin on day 1 p.c. Deciduogenic
      stimulus was given on day 5 p.c. Treatment of cyproterone acetate (10 mg kg(-1))
      was scheduled from day 5 through day 9 p.c. Animals were killed on day 10 p.c,
      and the degree of endometrial decidual growth, plasma levels of oestradiol,
      progesterone, ACTH and testosterone were determined. Results showed that compared
      to controls there was a concomitant drop in endometrial decidual growth
      concurrently with impaired levels of oestradiol and progesterone in diabetic
      pseudopregnant rats. ACTH and testosterone levels were, however, profoundly
      elevated. Cyproterone acetate treatment in the diabetic pseudopregnant rat
      resulted in a simultaneous elevation of oestradiol and progesterone, which
      eventually helped the endometrial differentiation to decidua in the diabetic
      pseudopregnant rat parallel to controls. Present experimental data suggest that
      diabetes-associated impaired endometrial decidualization in the pseudopregnant
      rat is possibly caused by testosterone-induced oestrogen deficiency.

PMID- 10887051
TI  - Effects of some medical drugs on enzyme activities of carbonic anhydrase from
      human erythrocytes in vitro and from rat erythrocytes in vivo.
AB  - In this study, firstly, the effects of sodium ampicillin, magnesium sulfate, and
      sodium dipyrone on human carbonic anhydrase (HCA) (EC 4.2.1.1.) isozymes have
      been investigated in vitro. Human erythrocyte CA-I and CA-II isozymes were
      separately purified by affinity chromatography. Inhibition or activation effects
      of three different medical drugs on HCA isozymes were determined using the CO(2)
      Hydratase method by plotting activity %vs [medical drug]. I(50)values of the
      drugs exhibiting inhibition effects were found by means of these graphs. It was
      observed on HCA-I hydratase activity that sodium ampicillin and sodium dipyrone
      showed inhibition and activation effects, respectively. However, magnesium
      sulfate showed no effect. It was observed on HCA-II hydratase activity that
      sodium ampicillin and magnesium sulfate showed an inhibition effect, and sodium
      dipyrone showed an activation effect. In addition, in vivo studies were performed
      for these medical drugs in Sprague-Dawley rats. It was demonstrated that CA in
      erythrocytes was significantly inhibited by these drugs in 3 h.

PMID- 10887052
TI  - Fatigue in chronic disease.
AB  - Fatigue is an extremely common complaint among patients with chronic disease.
      However, because of the subjective nature of fatigue, and the lack of effective
      therapeutics with which to treat fatigue, this symptom is often ignored by
      clinicians, who instead focus on hard, objective disease end-points. Recently,
      the symptom of fatigue has received greater attention as part of overall health
      related quality of life assessments in patients with chronic disease.
      Furthermore, new methods are being developed to help quantify fatigue, and are
      being utilized more frequently in the clinical setting. Moreover, studies in
      patients and using animal models of disease have provided some insight into
      changes within the brain which appear to be linked to the genesis of central
      fatigue. This review focuses on fatigue in chronic disease and outlines possible
      mechanisms which may give rise to central fatigue in chronic disease. Moreover,
      methods for measuring fatigue and an approach to the fatigued patient are
      discussed. Hopefully, a broader understanding of this distressing symptom will
      lead to the development of specific therapies for treating fatigue in these
      patients.

PMID- 10887053
TI  - Molecular basis of human natural killer cell recognition of HLA-E (human
      leucocyte antigen-E) and its relevance to clearance of pathogen-infected and
      tumour cells.
AB  - HLA-E (human leucocyte antigen-E) is a conserved class I major histocompatibility
      molecule which has only limited polymorphism. It binds to the leader peptide
      derived from the polymorphic classical major histocompatibility molecules HLA-A,
      HLA-B and HLA-C. This peptide binding is highly specific and stabilizes the HLA-E
      protein, allowing it to migrate to the cell surface. A functioning TAP
      (transporter associated with antigen processing) molecule is required to
      transport these peptides into the endoplasmic reticulum, where they can interact
      with HLA-E. HLA-E then migrates to the cell surface, where it interacts with
      CD94/NKG2A receptors on natural killer cells. This interaction inhibits natural
      killer cell-mediated lysis of a cell displaying HLA-E. If the leader peptide is
      not present in the endoplasmic reticulum, HLA-E is unstable and is degraded
      before it reaches the cell surface. In damaged cells, such as virally infected or
      tumour cells, down-regulation of HLA-A, HLA-B and HLA-C production or inhibition
      of TAP prevents stabilization of HLA-E by the leader peptide. Under these
      circumstances, HLA-E does not reach the cell surface and the cell is then
      vulnerable to lysis by natural killer cells. The molecular mechanisms underlying
      this function of HLA-E have been revealed by crystallographic studies of the
      structure of HLA-E.

PMID- 10887054
TI  - The angiotensinogen gene 235T variant is associated with an increased risk of
      restenosis after percutaneous transluminal coronary angioplasty.
AB  - The therapeutic benefit of percutaneous transluminal coronary angioplasty (PTCA)
      is limited by restenosis in 30-40% of patients. The underlying mechanisms are
      currently not well understood. Besides clinical and angiographic variables,
      genetic factors may be involved. In the present study, we investigated the
      associations between the angiotensinogen T174M and M235T, the angiotensin I
      converting enzyme (ACE) I/D and the angiotensin II type 1 receptor A1166C gene
      polymorphisms and restenosis in 511 patients who had undergone successful PTCA
      (without stenting) and follow-up angiography. Clinical and angiographic variables
      were also considered as possible predictors of restenosis. Stenosis severity was
      estimated by visual inspection of the angiograms. Altogether, 160 patients had
      restenosis, as defined by a greater than 50% reduction in the diameter of the
      dilated segment at follow-up angiography compared with the findings immediately
      following angioplasty. There were significantly more carriers of the
      angiotensinogen 235T allele and more patients with the ACE DD genotype in the
      restenosis group than in the no restenosis group, but only the angiotensinogen
      235T allele (and not the ACE DD genotype) remained significantly associated with
      restenosis following multifactorial analyses. No differences between the two
      groups were found with respect to the other gene polymorphisms. Patients who
      subsequently developed restenosis had a higher degree of stenosis and more severe
      lesions before PTCA, as well as less residual stenosis immediately after PTCA. We
      conclude that the angiotensinogen M235T gene polymorphism may be an independent
      predictor of restenosis after PTCA.

PMID- 10887055
TI  - First clinical trial with etomoxir in patients with chronic congestive heart
      failure.
AB  - In the failing human myocardium, both impaired calcium homoeostasis and
      alterations in the levels of contractile proteins have been observed, which may
      be responsible for reduced contractility as well as diastolic dysfunction. In
      addition, levels of a key protein in calcium cycling, i.e. the sarcoplasmic
      reticulum Ca(2+)-ATPase, and of the alpha-myosin heavy chain have been shown to
      be enhanced by treatment with etomoxir, a carnitine palmitoyltransferase
      inhibitor, in normal and pressure-overloaded rat myocardium. We therefore
      studied, for the first time, the influence of long-term oral application of
      etomoxir on cardiac function in patients with chronic heart failure. A dose of 80
      mg of etomoxir was given once daily to 10 patients suffering from heart failure
      (NYHA functional class II-III; mean age 55+/-4 years; one patient with ischaemic
      heart disease and nine patients with dilated idiopathic cardiomyopathy; all
      male), in addition to standard therapy. The left ventricular ejection fraction
      was measured echocardiographically before and after a 3-month period of
      treatment. Central haemodynamics at rest and exercise (supine position bicycle)
      were defined by means of a pulmonary artery catheter and thermodilution. All 10
      patients improved clinically; no patient had to stop taking the study medication
      because of side effects; and no patient died during the 3-month period. Maximum
      cardiac output during exercise increased from 9.72+/-1.25 l/min before to 13.44+/
      1.50 l/min after treatment (P<0.01); this increase was mainly due to an increased
      stroke volume [84+/-7 ml before and 109+/-9 ml after treatment (P<0.01)]. Resting
      heart rate was slightly reduced (not statistically significant). During exercise,
      for any given heart rate, stroke volume was significantly enhanced (P<0.05). The
      left ventricular ejection fraction increased significantly from 21.5+/-2.6% to
      27.0+/-2.3% (P<0.01). In acute studies, etomoxir showed neither a positive
      inotropic effect nor vasodilatory properties. Thus, although the results of this
      small pilot study are not placebo-controlled, all patients seem to have
      benefitted from etomoxir treatment. Etomoxir, which has no acute inotropic or
      vasodilatory properties and is thought to increase gene expression of the
      sarcoplasmic reticulum Ca(2+)-ATPase and the alpha-myosin heavy chain, improved
      clinical status, central haemodynamics at rest and during exercise, and left
      ventricular ejection fraction.

PMID- 10887056
TI  - Effects of hyperglycaemia and hyperinsulinaemia on proximal gastric motor and
      sensory function in humans.
AB  - During acute hyperglycaemia, gastric emptying is delayed and the compliance of
      the proximal stomach is increased significantly. It is not known whether the
      effect of hyperglycaemia on proximal gastric motor function in healthy volunteers
      results from endogenous hyperinsulinaemia. Therefore we studied the effects of
      acute hyperglycaemia and hyperinsulinaemia on proximal gastric function, measured
      using an electronic barostat. Eight healthy volunteers were studied on three
      separate occasions during: (a) normoglycaemia, (b) hyperglycaemic
      hyperinsulinaemic clamping, and (c) euglycaemic hyperinsulinaemic clamping.
      Gastric compliance was significantly (P<0.01) increased during hyperglycaemia
      (44+/-5 ml/mmHg), and also during hyperinsulinaemia (38+/-4 ml/mmHg), compared
      with during normoglycaemia (31+/-3 ml/mmHg). During pressure distension,
      sensations of fullness were greater during hyperglycaemia and during
      hyperinsulinaemia compared with controls. At a set pressure of minimal distension
      pressure +2 mmHg, the intrabag volume was significantly higher during
      hyperglycaemia (292+/-36 ml; P<0.05), but not during hyperinsulinaemia (161+/-35
      ml), compared with during normoglycaemia (129+/-10 ml). Postprandial relaxation
      was significantly (P<0.01) decreased during hyperglycaemia (93+/-64 ml) and
      hyperinsulinaemia (101+/-64 ml) compared with normoglycaemia (224+/-56 ml). Thus
      not only hyperglycaemia, but also hyperinsulinaemia, influences proximal gastric
      compliance, postprandial relaxation and symptom perception.

PMID- 10887057
TI  - On the mechanism of growth hormone-induced stimulation of renal acidification in
      humans: effect of dietary NaCl.
AB  - Sustained administration of growth hormone (GH) to human subjects with NH(4)Cl
      induced chronic metabolic acidosis (CMA) results in a large (4.5+/-0.5 mmol/l)
      increase in the plasma HCO(3-) concentration, as mediated by a large increase in
      renal net acid excretion. The renal mechanism(s) responsible for the potent
      stimulation of renal hydrogen ion secretion by GH remain to be elucidated.
      Accordingly, we have assessed the Na(+) dependence of prolonged GH-stimulated
      renal acidification in four normal NaCl-restricted subjects (Na(+) intake 0.3
      mmol x kg(-1) x day(-1)) during CMA (4.2 mmol of NH(4)Cl x kg(-1) x day(-1) for 7
      days), CMA plus GH (0.1 unit/kg every 12 h for 5 days) and then CMA plus GH plus
      NaCl (1.7 mmol x kg(-1) x day(-1) for 6 days). During CMA, urine Na(+) excretion
      averaged 22.4+/-4.1 mmol/24 h. In response to GH administration, urinary net acid
      excretion was essentially unchanged, and the accumulated increment over 5 days of
      GH treatment was not different from zero (14+/-12 mmol; not significant). The
      plasma HCO(3)(-) concentration increased only slightly, from 14.2+/-0.8 to 15.0+/
      1.1 mmol/l (P<0.05). Despite the constraint on net acid excretion imposed by NaCl
      restriction, renal ammonia production increased, as suggested by increases in
      urine pH from 5.58+/-0.05 to 5.82+/-0.04 (P<0.005) and unchanged NH(4)(+)
      excretion (202+/-17 to 211+/-19 mmol/24 h; not significant). In response to
      dietary NaCl, urine pH decreased to 5.27+/-0.1 (P<0.001) and a large increment in
      net acid excretion accumulated (233+/-20 mmol; P<0.05), in association with an
      increase in plasma HCO(3-) to 18.7+/-1.3 mmol/l (P<0.001), a plasma HCO(3-) value
      similar to that reported previously in salt-replete, NH(4)Cl- fed subjects. These
      results demonstrate for the first time in any species that the acid excretory
      effect of GH administration is critically dependent on the availability of a
      surfeit of Na(+) for tubular reabsorption. GH and/or insulin-like growth factor-1
      affect renal acid excretion proximally (by stimulation of NH(3) production) and
      by a Na(+)-transport-dependent mechanism in the collecting duct (voltage-driven
      acidification) in humans. The present results indicate that an isolated increase
      in renal NH(3) production is insufficient to obligate an increase in net acid
      excretion.

PMID- 10887058
TI  - Supplemental oxygen does not modulate responses to acetylcholine or ascorbic acid
      in the forearm of patients with congestive heart failure.
AB  - Despite providing symptomatic relief in patients with congestive heart failure
      (CHF), supplemental oxygen (O(2)) has been demonstrated to increase total
      peripheral resistance. The present study investigated the possibility that O(2)
      inhalation reduces nitric oxide (NO) bioavailability, using endothelium-dependent
      (acetylcholine) and -independent (phentolamine) vasodilators, and the antioxidant
      ascorbic acid. Ten patients (nine male and one female) with primary left
      ventricular failure participated in the study. Forearm venous occlusion
      plethysmography was used to study blood flow responses to acetylcholine and the
      alpha-adrenergic antagonist phentolamine during inhalation of either room air or
      100% O(2), with and without the simultaneous infusion of ascorbic acid. Neither
      O(2) inhalation (3.9+/-0.4 compared with 3.8+/-0.3 ml.min(-1).100 ml(-1)) nor
      ascorbic acid infusion (5.2+/-0.4 compared with 5.5+/-0.4 ml.min(-1).100 ml(-1))
      affected resting forearm blood flow. The percentage increase from basal blood
      flow after acetylcholine infusion was not altered by either O(2) inhalation or
      ascorbic acid infusion (room air, 140+/-55%; O(2), 118+/-46%; ascorbic acid,
      147+/-39%; ascorbic acid+O(2), 109+/-31%). O(2) inhalation did, however, reduce
      the dilation induced by phentolamine (room air, 131+/-24%; O(2), 80+/-14%;
      P<0.05). These data indicate that oxygen inhalation does not increase forearm
      vascular resistance. Secondly, preservation of reactivity to acetylcholine during
      O(2) inhalation suggests that degradation of NO by O(2)-derived free radicals is
      not enhanced. Attenuation of phentolamine-induced vasodilation during O(2)
      inhalation, however, implies increased adrenergic activity, which may possibly
      exacerbate the detrimental effects of elevated sympathetic activity in CHF.

PMID- 10887059
TI  - Relationship between the clinical features of neurological decompression illness
      and its causes.
AB  - There is dispute as to whether paradoxical gas embolism is an important
      aetiological factor in neurological decompression illness, particularly when the
      spinal cord is affected. We performed a blind case-controlled study to determine
      the relationship between manifestations of neurological decompression illness and
      causes in 100 consecutive divers with neurological decompression illness and 123
      unaffected historical control divers. The clinical effects of neurological
      decompression illness (including the sites of lesions and latency of onset) were
      correlated with the presence of right-to-left shunts, lung disease and a
      provocative dive profile. The prevalence and size of shunts determined by
      contrast echocardiography were compared in affected divers and controls. Right-to
      left shunts, particularly those which were large and present without a Valsalva
      manoeuvre, were significantly more common in divers who had neurological
      decompression illness than in controls (P<0.001). Shunts graded as large or
      medium in size were present in 52% of affected divers and 12.2% of controls
      (P<0.001). Spinal decompression illness occurred in 26 out of 52 divers with
      large or medium shunts and in 12 out of 48 without (P<0.02). The distribution of
      latencies of symptoms differed markedly in the 52 divers with a large or medium
      shunt and in the 30 divers who had lung disease or a provocative dive profile. In
      most cases of neurological decompression illness the cause can be determined by
      taking a history of the dive profile and latency of onset, and by performing
      investigations to detect a right-to-left shunt and lung disease. Using this
      information it is possible to advise divers on the risk of returning to diving
      and on ways of reducing the risk if diving is resumed. Most cases of spinal
      decompression illness are associated with a right-to-left shunt.

PMID- 10887060
TI  - Aging reduces the responsiveness of coronary arteries from male Wistar rats to
      the vasodilatory action of testosterone.
AB  - This study was performed to examine whether aging affects the vasodilatory
      effects of testosterone in the coronary arteries of male rats. Isolated coronary
      arteries from young mature (3-4 months) and elderly (22-26 months) male Wistar
      rats were studied in a wire myograph. Contractile function and endothelial
      function were assessed by measuring vasomotor responses to 10-100 mmol/l KCl, 0.1
      mmol/l prostaglandin F(2alpha) (PGF(2alpha)) and 10 micromol/l acetylcholine.
      Sensitivity to the vasodilatory effects of testosterone was assessed by
      constructing dose-response curves to concentrations between 1 micromol/l and 1
      mmol/l testosterone dissolved in water in vessels maximally preconstricted with
      PGF(2alpha). The compliance characteristics of each vessel and serum testosterone
      levels from each animal were measured. Histological sections of myocardium were
      examined for differences in coronary artery morphology. Vessels from elderly
      animals were significantly more resistant to the vasodilatory effects of
      testosterone than vessels from young animals (P=0.001 by analysis of covariance).
      Vessels from elderly animals were also significantly less compliant (7.32+/-0.43
      microm/mN, compared with 10.99+/-1.52 microm/mN in young animals; P=0.011), and
      the levels of circulating testosterone in elderly animals were lower, but not
      significantly so (2.04+/-0.63 nmol/l compared with 3.88+/-1.7 nmol/l; P=0.32).
      Vessels from elderly animals were less contractile in response to KCl than those
      from young animals (P=0.004 by analysis of covariance). There were no significant
      differences between the two groups in their responses to PGF(2alpha) or
      acetylcholine. Thus it is concluded that coronary arteries from elderly rats are
      significantly less sensitive to the vasodilatory effects of testosterone than
      those from young animals.

PMID- 10887061
TI  - Elevated circulating cardiotrophin-1 in heart failure: relationship with
      parameters of left ventricular systolic dysfunction.
AB  - Cardiotrophin-1 (CT-1) is a cytokine that has been implicated as a factor
      involved in myocardial remodelling. The objective of the present study was to
      establish the relationship between circulating levels of CT-1 and measures of
      left ventricular size and systolic function in patients with heart failure. We
      recruited 15 normal subjects [six male; median age 60 years (range 30-79 years)]
      and 15 patients [11 male; median age 66 years (range 43-84 years)] with a
      clinical diagnosis of heart failure and echocardiographic left ventricular
      systolic dysfunction (LVSD). Echocardiographic variables (left ventricular wall
      motion index, end-diastolic and -systolic volumes, stroke volume, fractional
      shortening) and plasma CT-1 levels were determined. In patients with LVSD [median
      wall motion index 0.6 (range 0.3-1.4)], CT-1 was elevated [median 110.4 fmol/ml
      (range 33-516 fmol/ml)] compared with controls [wall motion index 2 in all cases;
      median CT-1 level 34.2 fmol/ml (range 6.9-54.1 fmol/ml); P<0.0001]. Log CT-1 was
      correlated with log wall motion index (r=-0.76, P<0.0001), log left ventricular
      end-systolic volume (r=0.54, P<0.05), stroke volume (r=-0.60, P=0.007) and log
      fractional shortening (r=-0.70, P=0.001). In a multivariate model of the
      predictors of log wall motion index, the only significant predictor was log CT-1
      (R(2)=56%, P=0.006). This is the first assessment of the relationship between
      plasma CT-1 levels and the degree of LVSD in humans, and demonstrates that CT-1
      is elevated in heart failure in relation to the severity of LVSD.

PMID- 10887062
TI  - The Pro-115 --> Gln mutation in peroxisome-proliferator-activated receptor (PPAR)
      gamma2 is extremely rare in a large cohort of U.S. Caucasians.

PMID- 10887063
TI  - Cardiotrophin-1: a new cardiac marker?

PMID- 10887064
TI  - Hair cells, hearing and hopping: a field guide to hair cell physiology in the
      frog.
AB  - For more than four decades, hearing in frogs has been an important source of
      information for those interested in auditory neuroscience, neuroethology and the
      evolution of hearing. Individual features of the frog auditory system can be
      found represented in one or many of the other vertebrate classes, but
      collectively the frog inner ear represents a cornucopia of evolutionary
      experiments in acoustic signal processing. The mechano-sensitive hair cell, as
      the focal point of transduction, figures critically in the encoding of acoustic
      information in the afferent auditory nerve. In this review, we provide a short
      description of how auditory signals are encoded by the specialized anatomy and
      physiology of the frog inner ear and examine the role of hair cell physiology and
      its influence on the encoding of sound in the frog auditory nerve. We hope to
      demonstrate that acoustic signal processing in frogs may offer insights into the
      evolution and biology of hearing not only in amphibians but also in reptiles,
      birds and mammals, including man.

PMID- 10887065
TI  - Locomotion in scombrid fishes: morphology and kinematics of the finlets of the
      chub mackerel Scomber japonicus.
AB  - Finlets are small non-retractable fins located on the dorsal and ventral margins
      of the body between the second dorsal and anal fins and the tail of scombrid
      fishes. The morphology of the finlets, and finlet kinematics during swimming in a
      flow tank at speeds of 0.8-3. 0 fork lengths s(-1), were examined in the chub
      mackerel Scomber japonicus. Functionally, S. japonicus has five dorsal and anal
      triangular finlets (the fifth finlet is a pair of finlets acting in concert).
      Slips of muscle that insert onto the base of each finlet indicate the potential
      for active movement. In animals of similar mass, finlet length and area increased
      posteriorly. Finlet length, height and area show positive allometry in animals
      from 45 to 279 g body mass. Summed finlet area was approximately 15 % of caudal
      fin area. During steady swimming, the finlets typically oscillated symmetrically
      in the horizontal and vertical planes. Finlet excursions in the x, y and z
      directions ranged from 1 to 5 mm, increased posteriorly and were independent of
      speed. The timing of the maximum amplitude of oscillation was phased posteriorly;
      the phase lag of the maximum amplitude of oscillation was independent of speed.
      During some periods of gliding, a finlet occasionally moved independently of the
      body and the other finlets, which indicated active control of finlet movement.
      The angle of attack of the finlets averaged approximately 0 degrees over a
      tailbeat, indicating no net contribution to thrust production via classical lift
      based mechanisms. However, the timing of finlet movement relative to that of the
      tail suggests that more posterior finlets may direct some flow longitudinally as
      the tail decelerates and thereby contribute flow to the developing caudal fin
      vortex.

PMID- 10887066
TI  - Three-dimensional kinematics and wake structure of the pectoral fins during
      locomotion in leopard sharks Triakis semifasciata.
AB  - The classical theory of locomotion in sharks proposes that shark pectoral fins
      are oriented to generate lift forces that balance the moment produced by the
      oscillating heterocercal tail. Accordingly, previous studies of shark locomotion
      have used fixed-wing aircraft as a model assuming that sharks have similar
      stability and control mechanisms. However, unlike airplanes, sharks are propelled
      by undulations of the body and tail and have considerable control of pectoral fin
      motion. In this paper, we use a new approach to examine the function of the
      pectoral fins of leopard sharks, Triakis semifasciata, during steady horizontal
      swimming at speeds of 0.5-2.0ls(-1), where l is total body length, and during
      vertical maneuvering (rising and sinking) in the water column. The planar
      orientation of the pectoral fin was measured using three-dimensional kinematics,
      while fluid flow in the wake of the pectoral fin and forces exerted on the water
      by the fin were quantified using digital particle image velocimetry (DPIV).
      Steady horizontal swimming in leopard sharks is characterized by continuous
      undulations of the body with a positive body tilt to the flow that decreases from
      a mean of 11 degrees to 0.6 degrees with increasing flow speeds from 0. 5 to
      2.0ls(-1). Three-dimensional analysis showed that, during steady horizontal
      locomotion, the pectoral fins are cambered, concave downwards, at a negative
      angle of attack that we predict to generate no significant lift. Leopard shark
      pectoral fins are also oriented at a substantial negative dihedral angle that
      amplifies roll moments and hence promotes rapid changes in body position.
      Vortices shed from the trailing edge of the pectoral fin were detected only
      during vertical maneuvering. Starting vortices are produced when the posterior
      plane of the pectoral fin is actively flipped upwards or downwards to initiate
      rising or sinking, respectively, in the water column. The starting vortex
      produced by the pectoral fin induces a pitching moment that reorients the body
      relative to the flow. Body and pectoral fin surface angle are altered
      significantly when leopard sharks change vertical position in the water column.
      Thus, locomotion in leopard sharks is not analogous to flight in fixed-wing
      aircraft. Instead, a new force balance for swimming leopard sharks is proposed
      for steady swimming and maneuvering. Total force balance on the body is adjusted
      by altering the body angle during steady swimming as well as during vertical
      maneuvering, while the pectoral fins appear to be critical for initiating
      maneuvering behaviors, but not for lift production during steady horizontal
      locomotion.

PMID- 10887067
TI  - NaCl uptake by the branchial epithelium in freshwater teleost fish: an
      immunological approach to ion-transport protein localization.
AB  - Teleost fishes, living in fresh water, engage in active ion uptake to maintain
      ion homeostasis. Current models for NaCl uptake involve Na(+) uptake via an
      apical amiloride-sensitive epithelial Na(+) channel (ENaC), energized by an
      apical vacuolar-type proton pump (V-ATPase) or alternatively by an amiloride
      sensitive Na(+)/H(+) exchange (NHE) protein, and apical Cl(-) uptake mediated by
      an electroneutral, SITS-sensitive Cl(-)/HCO(3-) anion-exchange protein. Using non
      homologous antibodies, we have determined the cellular distributions of these ion
      transport proteins to test the predicted models. Na(+)/K(+)-ATPase was used as a
      cellular marker for differentiating branchial epithelium mitochondria-rich (MR)
      cells from pavement cells. In both the freshwater tilapia (Oreochromis
      mossambicus) and rainbow trout (Oncorhynchus mykiss), V-ATPase and ENaC-like
      immunoreactivity co-localized to pavement cells, although apical labelling was
      also found in MR cells in the trout. In the freshwater tilapia, apical anion
      exchanger-like immunoreactivity is found in the MR cells. Thus, a freshwater-type
      MR chloride cell exists in teleost fishes. The NHE-like immunoreactivity is
      associated with the accessory cell type and with a small population of pavement
      cells in tilapia.

PMID- 10887068
TI  - Immunolocalization of ion-transport proteins to branchial epithelium mitochondria
      rich cells in the mudskipper (Periophthalmodon schlosseri).
AB  - The branchial epithelium of the mudskipper Periophthalmodon schlosseri is densely
      packed with mitochondria-rich (MR) cells. This species of mudskipper is also able
      to eliminate ammonia against large inward gradients and to tolerate extremely
      high environmental ammonia concentrations. To test whether these branchial MR
      cells are the sites of active ammonia elimination, we used an immunological
      approach to localize ion-transport proteins that have been shown
      pharmacologically to be involved in the elimination of NH(4)(+) (Na(+)/NH(4)(+)
      exchanger and Na(+)/NH(4)(+)-ATPase). We also investigated the role of carbonic
      anhydrase and boundary-layer pH effects in ammonia elimination by using the
      carbonic anhydrase inhibitor acetazolamide and by buffering the bath water with
      Hepes, respectively. In the branchial epithelium, Na(+)/H(+) exchangers (both
      NHE2- and NHE3-like isoforms), a cystic fibrosis transmembrane regulator (CFTR)
      like anion channel, a vacuolar-type H(+)-ATPase (V-ATPase) and carbonic anhydrase
      immunoreactivity are associated with the apical crypt region of MR cells.
      Associated with the MR cell basolateral membrane and tubular system are the
      Na(+)/K(+)-ATPase and a Na(+)/K(+)/2Cl(-) cotransporter. A proportion of the
      ammonia eliminated by P. schlosseri involves carbonic anhydrase activity and is
      not dependent on boundary-layer pH effects. The apical CFTR-like anion channel
      may be serving as a HCO(3)(-) channel accounting for the acid-base neutral
      effects observed with net ammonia efflux inhibition.

PMID- 10887069
TI  - Humboldt penguins outmanoeuvring El Nino.
AB  - We satellite-tracked five Humboldt penguins during the strong 1997/98 El Nino
      Southern Oscillation (ENSO) from their breeding island Pan de Azucar (26 degrees
      09'S, 70 degrees 40'W) in Northern Chile and related their activities at sea to
      satellite-derived information on sea surface temperature (SST), sea surface
      temperature anomaly (SSTA), wind direction and speed, chlorophyll a
      concentrations and statistical data on fishery landings. We found that Humboldt
      penguins migrated by up to 895 km as marine productivity decreased. The total
      daily dive duration was highly correlated with SSTA, ranging from 3.1 to 12.5 h
      when the water was at its warmest (+4 degrees C). Birds travelled between 2 and
      116 km every day, travelling further when SSTA was highest. Diving depths
      (maximum 54 m), however, were not increased with respect to previous years. Two
      penguins migrated south and, independently of each other, located an area of high
      chlorophyll a concentration 150 km off the coast. Humboldt penguins seem to use
      day length, temperature gradients, wind direction and olfaction to adapt to
      changing environmental conditions and to find suitable feeding grounds. This
      makes Humboldt penguins biological in situ detectors of highly productive marine
      areas, with a potential use in the verification of trends detected by remote
      sensors on board satellites.

PMID- 10887070
TI  - Seasonal changes in buoyancy and diving behaviour of adult grey seals.
AB  - Phocid seals go through dramatic seasonal changes in body mass and composition as
      a result of the spatial and temporal separation of foraging, reproduction and
      moulting. These changes in body fat content and body mass result in seasonal
      changes in buoyancy, which in turn may influence diving behaviour. We examined
      the longitudinal changes in buoyancy and diving behaviour of 14 adult grey seals
      (Halichoerus grypus) during two periods that represent maximal contrast in body
      mass and composition. During both the post-moulting (PM) and pre-breeding (PB)
      periods, grey seals were negatively buoyant. However, buoyancy increased by 47.9
      % between the PM and PB periods. Descent rate was significantly faster during the
      PM period (1.0+/-0.07 m s(-1)) than during the PB period (0.7+/-0.06 m s(-1)),
      suggesting that seals were aided by negative buoyancy during the downward portion
      of dives. Ascent rate was also significantly faster during the PM period (0.8+/
      0.06 m s(-1)) than during the PB period (0.6+/-0.05 m s(-1)), contradicting the
      prediction that more buoyant animals should ascend faster. The effects of drag
      could not account for this discrepancy. Dive depth and surface interval between
      dives did not differ significantly between the two periods. Similarly, the
      distribution of dive shapes used by individuals did not differ between the two
      periods. However, dive duration was significantly longer during the PB period
      than during the PM period (5.5+/-0.25 min compared with 4.4+/-0.24 min,
      respectively) as was time spent at the bottom of the dive (3.1+/-0.22 min
      compared with 2.5+/-0.15 min, respectively).

PMID- 10887071
TI  - Heat-shock protein expression is absent in the antarctic fish Trematomus
      bernacchii (family Nototheniidae).
AB  - The heat-shock response, the enhanced expression of one or more classes of
      molecular chaperones termed heat-shock proteins (hsps) in response to stress
      induced by high temperatures, is commonly viewed as a 'universal' characteristic
      of organisms. We examined the occurrence of the heat-shock response in a highly
      cold-adapted, stenothermal Antarctic teleost fish, Trematomus bernacchii, to
      determine whether this response has persisted in a lineage that has encountered
      very low and stable temperatures for at least the past 14-25 million years. The
      patterns of protein synthesis observed in in vivo metabolic labelling experiments
      that involved injection of (35)S-labelled methionine and cysteine into whole fish
      previously subjected to a heat stress of 10 degrees C yielded no evidence for
      synthesis of any size class of heat-shock protein. Parallel in vivo labelling
      experiments with isolated hepatocytes similarly showed significant amounts of
      protein synthesis, but no indication of enhanced expression of any class of hsp.
      The heavy metal cadmium, which is known to induce synthesis of hsps, also failed
      to alter the pattern of proteins synthesized in hepatocytes. Although stress
      induced chaperones could not be detected under any of the experimental condition
      used, solid-phase antibody (western) analysis revealed that a constitutively
      expressed 70 kDa chaperone was present in this species, as predicted on the basis
      of requirements for chaperoning during protein synthesis. Amounts of the
      constitutively expressed 70 kDa chaperone increased in brain, but not in gill,
      during 22 days of acclimation to 5 degrees C. The apparent absence of a heat
      shock response in this highly stenothermal species is interpreted as an
      indication that a physiological capacity observed in almost all other organisms
      has been lost as a result of the absence of positive selection during evolution
      at stable sub-zero temperatures. Whether the loss of the heat-shock response is
      due to dysfunctional genes for inducible hsps (loss of open reading frames or
      functional regulatory regions), unstable messenger RNAs, the absence of a
      functional heat-shock factor or some other lesion remains to be determined.

PMID- 10887072
TI  - Partial experience with the arc of the sun is sufficient for all-day sun compass
      orientation in homing pigeons, Columba livia.
AB  - The ability of animals to learn to use the sun for orientation has been explored
      in numerous species. In birds, there is conflicting evidence about the experience
      needed for sun compass orientation to develop. The prevailing hypothesis is that
      birds need entire daytime exposure to the arc of the sun to use the sun as an
      orientation cue. However, there is also some evidence indicating that, even with
      limited exposure to the arc of the sun, birds, like insects, can use the sun to
      orient at any time of day. We re-examine this issue in a study of compass
      orientation in a cue-controlled arena. Two groups of young homing pigeons
      received different exposure to the sun. The control group experienced the sun
      throughout the day; the experimental group experienced only the apparent descent
      of the sun. After 8 weeks of sun exposure, we trained both groups in the
      afternoon to find food in a specific compass direction in an outdoor arena that
      provided a view of the sun but not landmarks. We then tested the pigeons in the
      morning for their ability to use the morning sun as an orientation cue. The
      control group and the experimental group, which was exposed to the morning sun
      for the first time, succeeded in orienting in the training direction during test
      1. The orientation of the experimental group was no different from that of the
      control group, although the experimental first trial directional response
      latencies were greater than the control latencies. Subsequently, we continued
      training both groups in the afternoon and then tested the pigeons during the
      morning under complete cloud cover. Both groups displayed random directional
      responses under cloud cover, indicating that the observed orientation was based
      on the visibility of the sun. The data indicate that pigeons with limited
      exposure to the arc of the sun can, like insects, use the sun for orientation at
      any time of day.

PMID- 10887073
TI  - Cortisol increases Na(+)/K(+)-ATPase density in plasma membranes of gill chloride
      cells in the freshwater tilapia Oreochromis mossambicus.
AB  - The effect of cortisol on Na(+)/K(+)-ATPase expression in the gill chloride cells
      of tilapia Oreochromis mossambicus was studied by immunocytochemistry at the
      light and electron microscope levels. One of three doses of cortisol (low, 125 mg
      kg(-1 )food; middle, 375 mg kg(-1 )food; high, 750 mg kg(-1) food) was
      administered via the food (at a ration of 1.5 % of body mass) and the fish were
      sampled after 5 days. Plasma osmolality and Na(+) levels were elevated in the
      middle- and high-dose groups, and plasma cortisol levels in the high-dose groups.
      Hematocrit values were not affected by the treatments. Opercular membrane
      chloride cell density increased by 94 % and 286 % in the middle- and high-dose
      fish, respectively, whereas the gill chloride cell frequency increased by up to
      28 % maximally in the high-dose fish. Lamellar gill chloride cells were absent in
      the control and low-dose groups, but were observed in the middle- and high-dose
      groups. Cortisol increased the volume of the tubular membrane system in mature
      gill chloride cells. Quantification of immunogold-labelled Na(+)/K(+)-ATPase
      antigen (a 104 kDa protein species, as demonstrated by western blot) revealed
      that the high dose of cortisol increases the Na(+)/K(+)-ATPase density in the
      tubular system of chloride cells. This is the first direct evidence that cortisol
      not only increases chloride cell numbers but also Na(+)/K(+)-ATPase density in
      these cells.

PMID- 10887074
TI  - Molecular characterization of a urea transporter in the gill of the gulf toadfish
      (Opsanus beta).
AB  - Urea excretion by the gulf toadfish (Opsanus beta) has been shown in previous
      studies to be a highly pulsatile facilitated transport, with excretion probably
      occurring at the gill. The present study reports the isolation of an 1800 base
      pair (kb) cDNA from toadfish gill with one open reading frame putatively encoding
      a 475-residue protein, the toadfish urea transporter (tUT). tUT, the first
      teleostean urea transporter cloned, has high homology with UTs (facilitated urea
      transporters) cloned from mammals, an amphibian and a shark, and most closely
      resembles the UT-A subfamily. When expressed in Xenopus laevis oocytes, tUT
      increased urea permeability (as measured by [(14)C]urea uptake) five- to
      sevenfold, and this permeability increase was abolished by phloretin, a common
      inhibitor of other UTs. Northern analysis using the 1.8 kb clone was performed to
      determine the tissue distribution and dynamics of tUT mRNA expression. Of six
      tissues examined (gill, liver, red blood cells, kidney, skin and intestine), only
      gill showed expression of tUT mRNA, with a predominant band at 1.8 kb and a minor
      band at 3.5 kb. During several points in the urea pulse cycle of toadfish (0, 4,
      6, 12 and 18 h post-pulse), measured by excretion of [(14)C]urea into the water,
      gill mRNA samples were obtained. Expression of tUT mRNA was found to be largely
      invariant relative to expression of beta-actin mRNA over the pulse cycle. These
      results further confirm the gill localization of urea transport in the toadfish
      and suggest that tUT regulation (and the regulation of pulsatile urea excretion)
      is probably not at the level of mRNA control. The results are discussed in the
      context of the mechanisms of vasopressin-regulated UT-A in mammalian kidney and
      morphological data for the toadfish gill.

PMID- 10887075
TI  - Mechanisms of gastrointestinal copper absorption in the African walking catfish:
      copper dose-effects and a novel anion-dependent pathway in the intestine.
AB  - In mammals, copper (Cu) absorption occurs mostly in the small intestine, and some
      of the Cu transporters involved in its uptake have been characterised. In fish,
      however, the regions of the gut involved in Cu absorption and the membrane
      transport mechanisms responsible for gastrointestinal Cu uptake are unknown.
      Everted gut sacs and isolated perfused intestine of Clarias gariepinus were used
      to explore Cu absorption (at 22 degrees C). Gut sacs exposed to 100 micromol l(
      1) mucosal solution Cu ([Cu](m)) showed that Cu was mostly (70 %) absorbed in the
      middle and hind intestine. Most of the accumulated Cu was located in the mucosa.
      In perfused intestines, cumulative Cu absorption from the mucosal solution to the
      serosal perfusate was greatest at 10 micromol l(-1) [Cu](m) and decreased at
      higher values of [Cu](m), while tissue accumulation of Cu showed a dose-dependent
      elevation. Absorption efficiency therefore declined with increasing Cu dose, and
      basolateral transport was the limiting factor in Cu uptake. Serosal applications
      of the P-type ATPase inhibitor vanadate (100 micromol l(-1)) or the anion
      transport inhibitor DIDS (100 micromol l(-1)) caused threefold increases in net
      Cu uptake (at [Cu](m)=10 micromol l(-1)). The vanadate effect was explained by a
      reduction in transepithelial potential rather than inhibition of Cu-ATPase, but
      the DIDS effect was not. Transepithelial potential, water transport and tissue
      [Cu] were not affected by DIDS, but tissue [K(+)] was elevated. Removal of Cl(-)
      simultaneously from both the mucosal and serosal solutions caused a 10-fold
      reduction in the rate of Cu uptake, while removal of Cl(-) from the mucosal
      solution only completely abolished Cu absorption to the serosal perfusate.
      Transepithelial potential effects are discussed. We conclude that Cu absorption
      occurs mostly in the intestine and is normally driven by a basolateral Cu/anion
      symport that prefers Cl(-).

PMID- 10887076
TI  - A series of novel mutants of Arabidopsis thaliana that are defective in the
      formation of continuous vascular network: calling the auxin signal flow
      canalization hypothesis into question.
AB  - For the genetic analysis of molecular mechanisms underlying temporal and spatial
      regulation of vascular pattern formation, we isolated mutants of Arabidopsis
      thaliana that are impaired in vascular patterning. Microscopic examination of the
      cotyledonary venation of 3,400 M(3) lines led to the identification of 12 mutant
      lines. Genetic analysis of 8 of these mutant lines indicated that vein pattern
      formation in these lines resulted from monogenic recessive mutations in 7
      different genes, designated VAN1 through VAN7. Mutations in VAN1 through VAN6
      genes caused fragmentation (disconnection or partial loss) of lateral veins of
      the cotyledon and tertiary veins of the rosette leaf whereas they were less
      injurious to the formation of major veins. Detailed characterization of the van3
      mutant using pAthb8::GUS and pTED3::GUS, as molecular markers for the early stage
      of vascular tissue formation showed that the provascular tissue of the
      cotyledonary lateral veins was differentiated in fragments during late
      embryogenesis. These phenotypes of the van mutants are discussed in relation to
      the auxin signal flow canalization hypothesis and the diffusion-reaction
      prepattern hypothesis, with the fragility of the continuity in the minor vein
      formation favoring the latter hypothesis.

PMID- 10887077
TI  - The SCARFACE gene is required for cotyledon and leaf vein patterning.
AB  - Mechanisms controlling vein patterning are poorly understood. We describe a
      recessive Arabidopsis mutant, scarface (sfc), which maps to chromosome 5. sfc
      mutants have vein pattern defects in cotyledons, leaves, sepals and petals. In
      contrast to the wild type, in which these organs all have linear veins that are
      continuous with at least one other vein, in sfc mutants these organs' secondary
      and tertiary veins are largely replaced by small segments of discontinuous veins,
      which we call vascular islands. Patterning defects are manifest in cotyledon
      provascular tissue, suggesting that the patterning defect occurs early in
      organogenesis. sfc mutants have exaggerated responses to exogenous auxin.
      Analysis of monopteros (mp(T370)) sfc-1 double mutants suggested that SFC has
      partially overlapping functions with MP in patterning of both primary and
      secondary veins.

PMID- 10887078
TI  - MesP1 and MesP2 are essential for the development of cardiac mesoderm.
AB  - The transcription factors, MesP1 and MesP2, sharing an almost identical bHLH
      motif, have an overlapping expression pattern during gastrulation and
      somitogenesis. Inactivation of the Mesp1 gene results in abnormal heart
      morphogenesis due to defective migration of heart precursor cells, but
      somitogenesis is not disrupted because of normal expression of the Mesp2 gene. To
      understand the cooperative functions of MesP1 and MesP2, either a deletion or
      sequential gene targeting strategy was employed to inactivate both genes. The
      double-knockout (dKO) embryos died around 9.5 days postcoitum (dpc) without
      developing any posterior structures such as heart, somites or gut. The major
      defect in this double-knockout embryo was the apparent lack of any mesodermal
      layer between the endoderm and ectoderm. The abnormal accumulation of cells in
      the primitive streak indicates a defect in the migratory activity of mesodermal
      cells. Molecular markers employed to characterize the phenotype revealed a lack
      of the cranio-cardiac and paraxial mesoderm. However, the axial mesoderm, as
      indicated by brachyury (T) expression, was initially generated but anterior
      extension was halted after 8.5 dpc. Interestingly, a headfold-like structure
      developed with right anterior-posterior polarity; however, the embryos lacked any
      posterior neural properties. The persistent and widely distributed expression of
      Cerberus-like-1(Cer1), Lim1 and Otx2 in the anterior endoderm might be
      responsible for the maintenance of anterior neural marker expression. We also
      performed a chimera analysis to further study the functions of MesP1 and MesP2 in
      the development of mesodermal derivatives. In the chimeric embryos, dKO cells
      were scarcely observed in the anterior-cephalic and heart mesoderm, but they did
      contribute to the formation of the somites, notochord and gut. These results
      strongly indicate that the defect in the cranial-cardiac mesoderm is cell
      autonomous, whereas the defect in the paraxial mesoderm is a non-cell-autonomous
      secondary consequence.

PMID- 10887079
TI  - Sperm extract injection into ascidian eggs signals Ca(2+) release by the same
      pathway as fertilization.
AB  - Injection of eggs of various species with an extract of sperm cytoplasm
      stimulates intracellular Ca(2+) release that is spatially and temporally like
      that occurring at fertilization, suggesting that Ca(2+) release at fertilization
      may be initiated by a soluble factor from the sperm. Here we investigate whether
      the signalling pathway that leads to Ca(2+) release in response to sperm extract
      injection requires the same signal transduction molecules as are required at
      fertilization. Eggs of the ascidian Ciona intestinalis were injected with the Src
      homology 2 domains of phospholipase C gamma or of the Src family kinase Fyn
      (which act as specific dominant negative inhibitors of the activation of these
      enzymes), and the effects on Ca(2+) release at fertilization or in response to
      injection of a sperm extract were compared. Our findings indicate that both
      fertilization and sperm extract injection initiate Ca(2+) release by a pathway
      requiring phospholipase C gamma and a Src family kinase. These results support
      the hypothesis that, in ascidians, a soluble factor from the sperm cytoplasm
      initiates Ca(2+) release at fertilization, and indicate that the activating
      factor from the sperm may be a regulator, directly or indirectly, of a Src family
      kinase in the egg.

PMID- 10887080
TI  - All Brn3 genes can promote retinal ganglion cell differentiation in the chick.
AB  - Targeted gene disruption studies in the mouse have demonstrated crucial roles for
      the Brn3 POU domain transcription factor genes, Brn3a, Brn3b, Brn3c (now called
      Pou4f1, Pou4f2, Pou4f3, respectively) in sensorineural development and survival.
      During mouse retinogenesis, the Brn3b gene is expressed in a large set of
      postmitotic ganglion cell precursors and is required for their early and terminal
      differentiation. In contrast, the Brn3a and Brn3c genes, which are expressed
      later in ganglion cells, appear to be dispensable for ganglion cell development.
      To understand the mechanism that causes the functional differences of Brn3 genes
      in retinal development, we employed a gain-of-function approach in the chick
      embryo. We find that Brn3b(l) and Brn3b(s), the two isoforms encoded by the Brn3b
      gene, as well as Brn3a and Brn3c all have similar DNA-binding and transactivating
      activities. We further find that the POU domain is minimally required for these
      activities. Consequently, we show that all these Brn3 proteins have a similar
      ability to promote development of ganglion cells when ectopically expressed in
      retinal progenitors. During chick retinogenesis, cBrn3c instead of cBrn3b
      exhibits a spatial and temporal expression pattern characteristic of ganglion
      cell genesis and its misexpression can also increase ganglion cell production.
      Based on these data, we propose that all Brn3 factors are capable of promoting
      retinal ganglion cell development, and that this potential may be limited by the
      order of expression in vivo.

PMID- 10887081
TI  - A role for the DP subunit of the E2F transcription factor in axis determination
      during Drosophila oogenesis.
AB  - The E2F family of transcription factors contributes to cell cycle control by
      regulating the transcription of DNA replication factors. Functional 'E2F' is a
      DNA-binding heterodimer composed of E2F and DP proteins. Drosophila contains two
      E2F genes (dE2F, dE2F2) and one DP gene (dDP). Mutation of either dE2F or dDP
      eliminates G(1)-S transcription of known replication factors during embryogenesis
      and compromises DNA replication. However, the analysis of these mutant phenotypes
      is complicated by the perdurance of maternally supplied gene function. To address
      this and to further analyze the role of E2F transcription factors in development
      we have phenotypically characterized mitotic clones of dDP mutant cells in the
      female germline. Our analysis indicates that dDP is required for several
      essential processes during oogenesis. In a fraction of the mutant egg chambers
      the germ cells execute one extra round of mitosis, suggesting that in this tissue
      dDP is uniquely utilized for cell cycle arrest rather than cell cycle
      progression. Mutation of dDP in the germline also prevents nurse cell cytoplasm
      transfer to the oocyte, resulting in a 'dumpless' phenotype that blocks oocyte
      development. This phenotype likely results from both disruption of the actin
      cytoskeleton and a failure of nurse cell apoptosis, each of which are required
      for normal cytoplasmic transfer. Lastly, we found that dDP is required for the
      establishment of the dorsal-ventral axis, as loss of dDP function prevents the
      localized expression of the EGFR ligand Gurken in the oocyte, which initiates
      dorsal-ventral polarity in the egg chamber. Thus we have uncovered new functions
      for E2F transcription factors during development, including an unexpected role in
      pattern formation.

PMID- 10887082
TI  - Suppression of the growth/differentiation transition in Dictyostelium development
      by transient expression of a novel gene, dia1.
AB  - In Dictyostelium discoideum Ax-2 cells, a specific checkpoint (PS point) from
      which cells enter the differentiation phase in response to starvation has been
      specified in the cell cycle. Using the differential display method, we isolated a
      novel gene, dia1 (differentiation-associated gene 1), that is specifically
      expressed in cells differentiating from the PS point. The dia1 mRNA has an open
      reading frame of 1,368 bp and is deduced to code for a 48.6 kDa protein (DIA1).
      The DIA1 protein is highly serine-rich and the serine residues are predominantly
      located in the C-terminal region. After the PSORT II search, the protein is
      predicted to be GPI-anchored at the plasma membrane. Unexpectedly, dia1
      overexpression rather impaired the progression of differentiation, possibly
      coupled with the reduced expression of early genes such as cAMP receptor1 (car1).
      The inhibitory effect of dia1 expression on early differentiation was almost
      completely nullified by externally applied cAMP pulses. In contrast to dia1
      overexpression, antisense RNA-mediated dia1 inactivation was found to enhance the
      initial step of cell differentiation, as exemplified by precocious expression of
      car1 and other early genes. We discuss the unique structure and function of DIA1
      in relation to the cooperative development of cells during the establishment of
      multicellular organization.

PMID- 10887083
TI  - Genetic control of epithelial tube size in the Drosophila tracheal system.
AB  - The proper size of epithelial tubes is critical for the function of the lung,
      kidney, vascular system and other organs, but the genetic and cellular mechanisms
      that control epithelial tube size are unknown. We investigated tube size control
      in the embryonic and larval tracheal (respiratory) system of Drosophila. A
      morphometric analysis showed that primary tracheal branches have characteristic
      sizes that undergo programmed changes during development. Branches grow at
      different rates and their diameters and lengths are regulated independently: tube
      length increases gradually throughout development, whereas tube diameter
      increases abruptly at discrete times in development. Cellular analysis and
      manipulation of tracheal cell number using cell-cycle mutations demonstrated that
      tube size is not dictated by the specific number or shape of the tracheal cells
      that constitute it. Rather, tube size appears to be controlled by coordinately
      regulating the apical (lumenal) surface of tracheal cells. Genetic analysis
      showed that tube sizes are specified early by branch identity genes, and the
      subsequent enlargement of branches to their mature sizes and maintenance of the
      expanded tubes involves a new set of genes described here, which we call tube
      expansion genes. This work establishes a genetic system for investigating tube
      size regulation, and provides an outline of the genetic program and cellular
      events underlying tracheal tube size control.

PMID- 10887084
TI  - Sonic hedgehog signaling at gastrula stages specifies ventral telencephalic cells
      in the chick embryo.
AB  - A secreted signaling factor, Sonic hedgehog (Shh), has a crucial role in the
      generation of ventral cell types along the entire rostrocaudal axis of the neural
      tube. At caudal levels of the neuraxis, Shh is secreted by the notochord and
      floor plate during the period that ventral cell fates are specified. At anterior
      prosencephalic levels that give rise to the telencephalon, however, neither the
      prechordal mesoderm nor the ventral neural tube expresses Shh at the time that
      the overt ventral character of the telencephalon becomes evident. Thus, the
      precise role and timing of Shh signaling relevant to the specification of ventral
      telencephalic identity remains unclear. By analysing neural cell differentiation
      in chick neural plate explants we provide evidence that neural cells acquire
      molecular properties characteristic of the ventral telencephalon in response to
      Shh signals derived from the anterior primitive streak/Hensen's node region at
      gastrula stages. Exposure of prospective anterior prosencephalic cells to Shh at
      this early stage is sufficient to initiate a temporal program of differentiation
      that parallels that of neurons generated normally in the medial ganglionic
      eminence subdivision of the ventral telencephalon.

PMID- 10887085
TI  - Novel cell-cell interactions during vulva development in Pristionchus pacificus.
AB  - Vulva development differs between Caenorhabditis elegans and Pristionchus
      pacificus in several ways. Seven of 12 ventral epidermal cells in P. pacificus
      die of apoptosis, whereas homologous cells in C. elegans fuse with the hypodermal
      syncytium. Vulva induction is a one-step process in C. elegans, but requires a
      continuous interaction between the gonad and the epidermis in P. pacificus. Here
      we describe several novel cell-cell interactions in P. pacificus, focusing on the
      vulva precursor cell P8.p and the mesoblast M. P8.p in P. pacificus, unlike its
      homologous cell in C. elegans, is incompetent to respond to gonadal signaling in
      the absence of other vulva precursor cells, but can respond to lateral signaling
      from a neighboring vulval precursor. P8.p provides an inhibitory signal that
      determines the developmental competence of P(5,7).p. This lateral inhibition acts
      via the mesoblast M and is regulated by the homeotic gene Ppa-mab-5. In Ppa-mab-5
      mutants, M is misspecified and provides inductive signaling to the vulval
      precursor cells, including P8.p. Taken together, vulva development in P.
      pacificus displays novel cell-cell interactions involving the mesoblast M and
      P8.p. In particular, P8.p represents a new ventral epidermal cell type, which is
      characterized by novel interactions and a specific response to gonadal signaling.

PMID- 10887086
TI  - Dpp signaling thresholds in the dorsal ectoderm of the Drosophila embryo.
AB  - The dorsal ectoderm of the Drosophila embryo is subdivided into different cell
      types by an activity gradient of two TGF(&bgr;) signaling molecules,
      Decapentaplegic (Dpp) and Screw (Scw). Patterning responses to this gradient
      depend on a secreted inhibitor, Short gastrulation (Sog) and a newly identified
      transcriptional repressor, Brinker (Brk), which are expressed in neurogenic
      regions that abut the dorsal ectoderm. Here we examine the expression of a number
      of Dpp target genes in transgenic embryos that contain ectopic stripes of Dpp,
      Sog and Brk expression. These studies suggest that the Dpp/Scw activity gradient
      directly specifies at least three distinct thresholds of gene expression in the
      dorsal ectoderm of gastrulating embryos. Brk was found to repress two target
      genes, tailup and pannier, that exhibit different limits of expression within the
      dorsal ectoderm. These results suggest that the Sog inhibitor and Brk repressor
      work in concert to establish sharp dorsolateral limits of gene expression. We
      also present evidence that the activation of Dpp/Scw target genes depends on the
      Drosophila homolog of the CBP histone acetyltransferase.

PMID- 10887087
TI  - Targeting of the EphA4 tyrosine kinase receptor affects dorsal/ventral
      pathfinding of limb motor axons.
AB  - The Eph family of tyrosine kinase receptors has recently been implicated in
      various processes involving the detection of environmental cues such as axonal
      guidance, targeted cell migration and boundary formation. We have inactivated the
      mouse EphA4 gene to investigate its functions during development. Homozygous
      EphA4 mutant animals show peroneal muscular atrophy correlating with the absence
      of the peroneal nerve, the main dorsal nerve of the hindlimb. This phenotype is
      also observed, although with a lower penetrance, in heterozygotes. During normal
      hindlimb innervation, motor axons converge towards the sciatic plexus region at
      the base of the limb bud, where they must choose between dorsal and ventral
      trajectories within the limb. Among the axons emerging from the sciatic plexus,
      dorsal projections show higher levels of EphA4 protein than ventral axons. In
      EphA4 mutant mice, presumptive dorsal motor axons fail to enter the dorsal
      compartment of the limb and join the ventral nerve. Our data therefore suggest
      that the level of EphA4 protein in growing limb motor axons is involved in the
      selection of dorsal versus ventral trajectories, thus contributing to the
      topographic organisation of motor projections.

PMID- 10887088
TI  - Jumeaux, a novel Drosophila winged-helix family protein, is required for
      generating asymmetric sibling neuronal cell fates.
AB  - The great majority of neurons in the Drosophila embryonic CNS are generated
      through two successive asymmetric cell divisions; neuroblasts (NBs) divide to
      produce another NB and a smaller ganglion mother cell (GMC); GMCs divide to
      generate two sibling neurons which can adopt distinct identities. During the
      division of the first born GMC from the NB4-2 lineage, GMC4-2a, Inscuteable
      (Insc) is localised to the apical cortex, Pon/Numb is localised to the basal
      cortex and two daughters with distinct identities, the RP2 motoneuron and its
      sibling RP2sib, are born. Resolution of distinct sibling neuronal fates requires
      correct apical localisation of Insc to facilitate the asymmetric localisation and
      preferential segregation of Pon/Numb to the basal daughter destined to become
      RP2. Here we report that jumeaux (jumu), which encodes a new member of the winged
      helix family of transcription factors, is required to mediate the asymmetric
      localisation and segregation of Pon/Numb but is dispensable for Insc apical
      localisation during the GMC4-2a cell division. In jumu mutants GMC4-2a Pon/Numb
      asymmetric localisation is defective and both daughter neurons can adopt the RP2
      identity. Jumu protein shows nuclear localisation and within the NB4-2 lineage is
      first detected only after the first neuroblast cell division, in GMC4-2a. Our
      results suggest that in addition to the correct formation of an apical complex,
      transcription mediated by Jumu is also necessary to facilitate the correct
      asymmetric localisation and segregation of Pon/Numb.

PMID- 10887089
TI  - A Caenorhabditis elegans type I TGF beta receptor can function in the absence of
      type II kinase to promote larval development.
AB  - The daf-4 gene encodes a type II bone morphogenetic protein receptor in
      Caenorhabditis elegans that regulates dauer larva formation, body size and male
      tail patterning. The putative type I receptor partner for DAF-4 in regulating
      dauer larva formation is DAF-1. Genetic tests of the mechanism of activation of
      these receptors show that DAF-1 can signal in the absence of DAF-4 kinase
      activity. A daf-1 mutation enhances dauer formation in a daf-4 null background,
      whereas overexpression of daf-1 partially rescues a daf-4 mutant. DAF-1 alone
      cannot fully compensate for the loss of DAF-4 activity, indicating that nondauer
      development normally results from the activities of both receptors. DAF-1
      signaling in the absence of a type II kinase is unique in the type I receptor
      family. The activity may be an evolutionary remnant, owing to daf-1's origin near
      the type I/type II divergence, or it may be an innovation that evolved in
      nematodes. daf-1 and daf-4 promoters both mediated expression of green
      fluorescent protein in the nervous system, indicating that a DAF-1/DAF-4 receptor
      complex may activate a neuronal signaling pathway. Signaling from a strong DAF
      1/DAF-4 receptor complex or a weaker DAF-1 receptor alone may provide larvae with
      more precise control of the dauer/nondauer decision in a range of environmental
      conditions.

PMID- 10887090
TI  - Molecular mechanisms of hormone-mediated Mullerian duct regression: involvement
      of beta-catenin.
AB  - Regression of the Mullerian duct in the male embryo is one unequivocal effect of
      anti-Mullerian hormone, a glycoprotein secreted by the Sertoli cells of the
      testis. This hormone induces ductal epithelial regression through a paracrine
      mechanism originating in periductal mesenchyme. To probe the mechanisms of action
      of anti-Mullerian hormone, we have studied the sequence of cellular and molecular
      events involved in duct regression. Studies were performed in male rat embryos
      and in transgenic mice overexpressing or lacking anti-Mullerian hormone, both in
      vivo and in vitro. Anti-Mullerian hormone causes regression of the cranial part
      of the Mullerian duct whereas it continues to grow caudally. Our work shows that
      this pattern of regression is correlated with a cranial to caudal gradient of
      anti-Mullerian hormone receptor protein, followed by a wave of apoptosis
      spreading along the Mullerian duct as its progresses caudally. Apoptosis is also
      induced by AMH in female Mullerian duct in vitro. Furthermore, apoptotic indexes
      are increased in Mullerian epithelium of transgenic mice of both sexes
      overexpressing the human anti-Mullerian hormone gene, exhibiting a positive
      correlation with serum hormone concentration. Inversely, apoptosis is reduced in
      male anti-Mullerian hormone-deficient mice. We also show that apoptosis is a
      decisive but not sufficient process, and that epitheliomesenchymal transformation
      is an important event of Mullerian regression. The most striking result of this
      study is that anti-Mullerian hormone action in peri-Mullerian mesenchyme leads in
      vivo and in vitro to an accumulation of cytoplasmic beta-catenin. The co
      localization of beta-catenin with lymphoid enhancer factor 1 in the nucleus of
      peri-Mullerian mesenchymal cells, demonstrated in primary culture, suggests that
      overexpressed beta-catenin in association with lymphoid enhancer factor 1 may
      alter transcription of target genes and may lead to changes in mesenchymal gene
      expression and cell fate during Mullerian duct regression. To our knowledge, this
      is the first report that beta-catenin, known for its role in Wnt signaling, may
      mediate anti-Mullerian hormone action.

PMID- 10887091
TI  - The homeodomain protein CePHOX2/CEH-17 controls antero-posterior axonal growth in
      C. elegans.
AB  - An essential aspect of a neuron's identity is the pattern of its axonal
      projections. In C. elegans, axons extend either longitudinally or
      circumferentially in response to distinct molecular cues, some of which have been
      identified. It is currently unclear, however, how the differential capacity to
      respond to these cues is transcriptionally implemented in distinct neuronal
      subtypes. Here, we characterise a C. elegans paired-like homeobox gene,
      CePhox2/ceh-17, expressed in five head neurons, ALA and the 4 SIAs, all of which
      project axons towards the tail along the lateral and sublateral cords. Abrogation
      of ceh-17 function, while leaving intact many phenotypic traits of these neurons,
      disrupts their antero-posterior axonal elongation beyond the mid-body region.
      Conversely, ectopic expression of ceh-17 in the mechanoreceptors, several of
      which are known to pioneer their tract, leads to exaggerated longitudinal axonal
      outgrowth. Thus, ceh-17 is a novel gene involved in fasciculation-independent
      longitudinal axonal navigation.

PMID- 10887092
TI  - Notch signaling regulates the pattern of auditory hair cell differentiation in
      mammals.
AB  - The development of the mammalian cochlea is an example of patterning in the
      peripheral nervous system. Sensory hair cells and supporting cells in the cochlea
      differentiate via regional and cell fate specification. The Notch signaling
      components shows both distinct and overlapping expression patterns of Notch1
      receptor and its ligands Jagged1 (Jag1) and Jagged2 (Jag2) in the developing
      auditory epithelium of the rat. On embryonic day 16 (E16), many precursor cells
      within the Kolliker's organ immunostained for the presence of both Notch1 and
      Jag1, while the area of hair cell precursors did not express either Notch1 and
      Jag1. During initial events of hair cell differentiation between E18 and birth,
      Notch1 and Jag1 expression predominated in supporting cells and Jag2 in nascent
      hair cells. Early after birth, Jag2 expression decreased in hair cells while the
      pattern of Notch1 expression now included both supporting cells and hair cells.
      We show that the normal pattern of hair cell differentiation is disrupted by
      alteration of Notch signaling. A decrease of either Notch1 or Jag1 expression by
      antisense oligonucleotides in cultures of the developing sensory epithelium
      resulted in an increase in the number of hair cells. Our data suggest that the
      Notch1 signaling pathway is involved in a complex interplay between the
      consequences of different ligand-Notch1 combinations during cochlear
      morphogenesis and the phases of hair cell differentiation.

PMID- 10887093
TI  - Tornado1 and tornado2 are required for the specification of radial and
      circumferential pattern in the Arabidopsis root.
AB  - The cell layers of the Arabidopsis primary root are arranged in a simple radial
      pattern. The outermost layer is the lateral root cap and lies outside the
      epidermis that surrounds the ground tissue. The files of epidermal and lateral
      root cap cells converge on a ring of initials (lateral root cap/epidermis
      initial) from which the epidermal and lateral root cap tissues of the seedling
      are derived, once root growth is initiated after germination. Each initial gives
      rise to a clone of epidermal cells and a clone of lateral root cap cells. These
      initial divisions in the epidermal/lateral root cap initial are defective in
      tornado1 (trn1) and trn2 plants indicating a requirement for TRN1 and TRN2 for
      initial cell function. Furthermore, lateral root cap cells develop in the
      epidermal position in trn1 and trn2 roots indicating that TRN1 and TRN2 are
      required for the maintenance of the radial pattern of cell specification in the
      root. The death of these ectopic lateral root cap cells in the elongation zone
      (where lateral root cap cells normally die) results in the development of gaps in
      the epidermis. These observations indicate that TRN1 and TRN2 are required to
      maintain the distinction between the lateral root cap and epidermis and suggest
      that lateral root cap fate is the default state. It also suggests that TRN1 and
      TRN2 repress lateral root cap fate in cells in the epidermal location.
      Furthermore, the position-dependent pattern of root hair and non-root hair cell
      differentiation in the epidermis is defective in trn1 and trn2 mutants. Together
      these results indicate that TRN1 and TRN2 are required for the maintenance of
      both the radial pattern of tissue differentiation in the root and for the
      subsequent circumferential pattern within the epidermis.

PMID- 10887094
TI  - The eli1 mutation reveals a link between cell expansion and secondary cell wall
      formation in Arabidopsis thaliana.
AB  - Mutants with altered patterns of lignification have been identified in a
      population of mutagenised Arabidopsis seedlings. One of the mutants exhibited
      ectopic lignification (eli) of cells throughout the plant that never normally
      lignify. The reduced expansion of eli1 cells resulted in a stunted phenotype, and
      xylem cells were misshapen and failed to differentiate into continuous strands,
      causing a disorganized xylem. Analysis of phenotypes associated with double
      mutants of eli1 lit (lion's tail), a cell expansion mutant, indicated that the
      primary defect in eli1 plants may be inappropriate initiation of secondary wall
      formation and subsequent aberrant lignification of cells caused by altered cell
      expansion. Related ectopic lignification phenotypes were also observed in other
      cell expansion mutants, suggesting a mechanism that senses cell size and controls
      subsequent secondary wall formation. Interactions between eli1 and wol
      (woodenleg), a mutant altering xylem cell specification, revealed a role for ELI1
      in promoting formation of continuous xylem strands, and demonstrated that ELI1
      functions during cell elongation zone in the primary root and other tissues.

PMID- 10887095
TI  - Introduction: the evolving role of bisphosphonate therapy in multiple myeloma.

PMID- 10887096
TI  - Stimulation of gammadelta T cells by aminobisphosphonates and induction of
      antiplasma cell activity in multiple myeloma.
AB  - Bisphosphonates are well-known inhibitors of osteoclastic bone resorption, but
      recent clinical reports support the possibility of direct or indirect antitumor
      effects by these compounds. Because bisphosphonates share structural homologies
      with recently identified gamma delta T-cell ligands, we examined the stimulatory
      capacity of bisphosphonates to gamma delta T cells and determined whether gamma
      delta T-cell stimulation by bisphosphonates could be exploited to generate
      antiplasma cell activity in multiple myeloma (MM). All tested
      aminobisphosphonates (alendronate, ibandronate, and pamidronate) induced
      significant expansion of gamma delta T cells (V gamma 9V delta 2++ subset) in
      peripheral blood mononuclear cell cultures of healthy donors at clinically
      relevant concentrations (half-maximal activity, 0.9-4 mcmol/L). The proliferative
      response of gamma delta T cells to aminobisphosphonates was IL-2 dependent,
      whereas activation of gamma delta T cells (up-regulation of CD25 and CD69)
      occurred in the absence of exogenous cytokines. Pamidronate-activated gamma delta
      T cells produced cytokines (ie, interferon [IFN]-gamma) and exhibited specific
      cytotoxicity against lymphoma (Daudi) and myeloma cell lines (RPMI 8226, U266).
      Pamidronate-treated bone marrow (BM) cultures of 24 patients with MM showed
      significantly reduced plasma cell survival compared with untreated cultures,
      especially in cultures in which activation of BM-gamma delta T cells was evident
      (14 of 24 patients with MM). gamma delta T-cell depletion from BM cultures
      completely abrogated the cytoreductive effect on myeloma cells in 2 of 3 tested
      patients with MM. These results show that aminobisphosphonates stimulating gamma
      delta T cells have pronounced effects on the immune system, which might
      contribute to the antitumor effects of these drugs. (Blood. 2000;96:384-392)

PMID- 10887098
TI  - Detection of differentially expressed genes in lymphomas using cDNA arrays:
      identification of clusterin as a new diagnostic marker for anaplastic large-cell
      lymphomas.
AB  - This study reports the first use of gene array technology for the identification
      of a tumor-specific marker in lymphoid neoplasms. The differential gene
      expression of 31 hematopoietic cell lines, representing most major lymphoma
      subgroups of B- and T-cell origin, was assessed by hybridizing labeled
      complementary DNA to Atlas human expression arrays containing 588 genes. Genes
      known to be specific for B, T, or myelomonocytic lineages were appropriately
      identified in the arrays, validating the general utility of this approach. One
      gene, clusterin, not previously known to be expressed in lymphoid neoplasms, was
      specifically found in all 4 anaplastic large-cell lymphoma (ALCL) cell lines, but
      not in any of the 27 remaining tumor lines. Using a monoclonal antibody against
      clusterin, its differential expression was confirmed by Western blotting and
      immunohistochemistry. A total of 198 primary lymphomas (representing most major
      lymphoma subtypes), including 36 cases of systemic ALCL, were surveyed for
      clusterin expression by immunohistochemistry and Western blotting. All of the 36
      ALCL cases marked for clusterin, with most cases showing moderate to strong
      staining in the majority of neoplastic cells. Clusterin expression was not
      related to expression of anaplastic lymphoma kinase-1. With 2 exceptions, none of
      the remaining 162 non-ALCL cases marked with the clusterin antibody, including
      Hodgkin disease and primary cutaneous ALCL. In reactive lymphoid tissues, only
      follicular dendritic cells and fibroblastic reticular cells exhibited staining.
      Clusterin is a highly conserved glycoprotein implicated in intercellular and cell
      matrix interactions, regulation of the complement system, lipid transport, stress
      responses, and apoptosis. Although its function in ALCL is unknown, the unique
      expression of clusterin within this category of lymphoma provides an additional
      marker for the diagnosis of ALCL. This study illustrates the enormous potential
      of gene array technologies for diagnostic marker discovery. (Blood. 2000;96:398
      404)

PMID- 10887097
TI  - Protein kinase inhibitors flavopiridol and 7-hydroxy-staurosporine down-regulate
      antiapoptosis proteins in B-cell chronic lymphocytic leukemia.
AB  - Compounds that inhibit protein kinases are currently undergoing clinical
      evaluation for the treatment of a variety of malignancies. The kinase inhibitors
      flavopiridol and 7 hydroxy-staurosporine (UCN-01) were examined for their effects
      on B-cell chronic lymphocytic leukemia (B-CLL) cells in vitro (n = 49).
      Flavopiridol and UCN-01 induced concentration-dependent apoptosis of most B-CLL
      samples tested, with greater than 50% cell killing occurring at concentrations of
      less than 1 mcmol/L, and with flavopiridol displaying more potent activity than
      UCN-01. Flavopiridol (0.1 mcmol/L) and UCN-01 (1 mcmol/L) also induced striking
      decreases in the levels of the antiapoptosis proteins Mcl-1, X-linked inhibitor
      of apoptosis (XIAP), and BAG-1 in nearly all cases of B-CLL and of Bcl-2 in
      approximately half of B-CLL specimens evaluated. In contrast, expression of the
      proapoptotic proteins Bax and Bak was not significantly influenced by these
      kinase inhibitors. Flavopiridol-induced decreases in the levels of antiapoptosis
      proteins Mcl-1 and XIAP preceded apoptosis and were not substantially affected by
      the addition of caspase inhibitors to cultures. In contrast, UCN-01-stimulated
      decreases in antiapoptosis proteins were slower, occurred concurrently with
      apoptosis, and were partially prevented by caspase inhibitors. The findings
      suggest that flavopiridol and UCN-01 induce apoptosis of B-CLL cells through
      different mechanisms. The potent apoptotic activities of flavopiridol and UCN-01
      against cultured B-CLL cells suggest that they may be effective as single agents
      in the treatment of B-CLL or for sensitizing B-CLL cells to conventional
      cytotoxic drugs. (Blood. 2000;96:393-397)

PMID- 10887099
TI  - Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes
      impaired recognition of intrinsic factor-vitamin B(12) by cubilin.
AB  - Megaloblastic anemia 1 (MGA1) is an autosomal recessive disorder caused by the
      selective intestinal malabsorption of intrinsic factor (IF) and vitamin
      B(12)/cobalamin (Cbl) in complex. Most Finnish patients with MGA1 carry the
      disease-specific P1297L mutation (FM1) in the IF-B(12) receptor, cubilin. By site
      directed mutagenesis, mammalian expression, and functional comparison of the
      purified wild-type and FM1 mutant forms of the IF-Cbl-binding cubilin region (CUB
      domains 5-8, amino acid 928-1386), we have investigated the functional
      implications of the P1297L mutation. Surface plasmon resonance analysis revealed
      that the P1297L substitution specifically increases the K(d) for IF-Cbl binding
      several-fold, largely by decreasing the association rate constant. In agreement
      with the binding data, the wild-type protein, but not the FM1 mutant protein,
      potently inhibits 37 degrees C uptake of iodine 125-IF-Cbl in cubilin-expressing
      epithelial cells. In conclusion, the data presented show a substantial loss in
      affinity of the FM1 mutant form of the IF-Cbl binding region of cubilin. This now
      explains the malabsorption of Cbl and Cbl-dependent anemia in MGA1 patients with
      the FM1 mutation. (Blood. 2000;96:405-409)

PMID- 10887100
TI  - The gastric marginal zone B-cell lymphoma of MALT type.

PMID- 10887101
TI  - The C-class chemokine, lymphotactin, impairs the induction of Th1-type
      lymphokines in human CD4(+) T cells.
AB  - Chemokines are involved in the regulation of leukocyte migration and for some of
      them, T-cell costimulation. To date, the only direct property of lymphotactin
      (Lptn), the unique member of the C class of chemokines, consists of T-cell
      chemoattraction. This report describes a novel function for Lptn in human T
      lymphocyte biology, by demonstrating the direct ability of Lptn to both inhibit
      and costimulate CD4(+) and CD8(+) T-cell activation, respectively. Lptn but not
      RANTES inhibited CD4(+) T-cell proliferation, through a decreased production of
      Th1 (interleukin [IL]-2, interferon [IFN]-gamma) but not Th2 (IL-4, IL-13)
      lymphokines, and decreased IL-2R alpha expression. Transfections in Jurkat cells
      showed a Lptn-mediated transcriptional down-regulation of gene-promoter
      activities specific for Th1-type lymphokines, as well as of nuclear factor of
      activated T cells (NF-AT) but not AP-1 or NF-KB enhancer activities. This
      suppressive action of Lptn could be compensated by overexpression of NF-ATc but
      not NF-ATp. CD4(+) T-cell proliferation was completely restored by exogenous IL-2
      or reversed by pertussis toxin, wortmannin, and genistein, suggesting the
      involvement of multiple partners in Lptn signaling. In contrast to CD4(+) cells,
      Lptn exerted a potent costimulatory activity on CD8(+) T-cell proliferation and
      IL-2 secretion. These data provide important insights into the role of Lptn in
      differential regulation of normal human T-cell activation and its possible
      implication in immune response disorders. (Blood. 2000;96:420-428)

PMID- 10887102
TI  - Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital
      neutropenia receiving G-CSF therapy.
AB  - Granulocyte colony-stimulating factor (G-CSF) has had a major impact on
      management of "severe chronic neutropenia," a collective term referring to
      congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G
      CSF with increased neutrophils, reduced infections, and improved survival. Some
      responders with congenital neutropenia have developed myelodysplastic syndrome
      and acute myeloblastic leukemia (MDS/AML), which raises the question of the role
      of G-CSF in pathogenesis. The Severe Chronic Neutropenia International Registry
      (SCNIR), Seattle, WA, has data on 696 neutropenic patients, including 352
      patients with congenital neutropenia, treated with G-CSF from 1987 to present.
      Treatment and patient demographic data were analyzed. The 352 congenital patients
      were observed for a mean of 6 years (range, 0.1-11 years) while being treated. Of
      these patients, 31 developed MDS/AML, for a crude rate of malignant
      transformation of nearly 9%. None of the 344 patients with idiopathic or cyclic
      neutropenia developed MDS/AML. Transformation was associated with acquired marrow
      cytogenetic clonal changes: 18 patients developed a partial or complete loss of
      chromosome 7, and 9 patients manifested abnormalities of chromosome 21 (usually
      trisomy 21). For each yearly treatment interval, the annual rate of MDS/AML
      development was less than 2%. No significant relationships between age at onset
      of MDS/AML and patient gender, G-CSF dose, or treatment duration were found (P
      >.15). In addition to the 31 patients who developed MDS/AML, the SCNIR also has
      data on 9 additional neutropenic patients whose bone marrow studies show
      cytogenetic clonal changes but the patients are without transformation to
      MDS/AML. Although our data does not support a cause-and-effect relationship
      between development of MDS/AML and G-CSF therapy or other patient demographics,
      we cannot exclude a direct contribution of G-CSF in the pathogenesis of MDS/AML.
      This issue is unclear because MDS/AML was not seen in cyclic or idiopathic
      neutropenia. Improved survival of congenital neutropenia patients receiving G-CSF
      therapy may allow time for the expression of the leukemic predisposition that
      characterizes the natural history of these disorders. However, other factors
      related to G-CSF may also be operative in the setting of congenital neutropenia.
      (Blood. 2000;96:429-436)

PMID- 10887103
TI  - Mortality among males with hemophilia: relations with source of medical care. The
      Hemophilia Surveillance System Project Investigators.
AB  - Although persons with hemophilia are known to be at increased risk of death, no
      studies have examined the source of medical care and other personal
      characteristics for associations with mortality. To determine death rates and to
      identify causes of death and predictors of mortality, we studied a cohort
      comprised of all hemophilic males identified by a six-state surveillance system.
      Data were obtained by medical record review of contacts with physicians,
      hemophilia treatment centers (HTCs), and other sources of care during 1993-1995
      and from death certificates. Factors examined included age, race, state of
      residence, health insurance type, medical care source, hemophilia type/severity,
      presence of inhibitor, liver disease, HIV infection, and AIDS. A total of 2950
      subjects were followed for an average of 2.6 years. Their median age was 22
      years; 73% were white, 79% had hemophilia A, 42% had severe disease, and 67% had
      visited an HTC. During 7575 person years (PYs) of observation, 236 persons died
      an age-adjusted mortality rate of 40.4 deaths/1000 PYs; 65% of deaths were HIV
      related. In addition to age, factors independently associated with increased risk
      of death (relative risk, P value) were the following: AIDS (33.5, <.001); HIV
      infection (4.7, <.001); liver disease (2.4, <.001); and Medicare/Medicaid
      insurance (1.4,. 01). Those persons who had received care in an HTC had a
      significantly decreased risk of death (0.6,.002). Although HIV infection and the
      presence of severe liver disease remain strong predictors of mortality, survival
      is significantly greater among hemophilics who receive medical care in HTCs.
      (Blood. 2000;96:437-442)

PMID- 10887104
TI  - Fulminant EBV(+) T-cell lymphoproliferative disorder following acute/chronic EBV
      infection: a distinct clinicopathologic syndrome.
AB  - This study describes the clinicopathologic features of 5 patients who developed a
      fulminant Epstein-Barr virus (EBV)-positive clonal T-cell lymphoproliferative
      disorder (LPD) after acute EBV infection. One additional patient developed a
      similar disorder in the setting of long-standing chronic active EBV infection.
      Detailed immunophenotyping, in situ hybridization for EBV early RNA-1 (EBER1) and
      polymerase chain reaction (PCR) analyses for immunoglobulin (Ig) heavy chain and
      T-cell receptor (TCR)-gamma gene rearrangements were performed on paraffin
      embedded tissue from all patients. In addition, EBV strain typing and detection
      of the characteristic 30-bp deletion of the latent membrane protein-1 (LMP-1)
      gene were performed by PCR. Controls included 8 cases of uncomplicated infectious
      mononucleosis (IM). Patients included 4 males and 2 females with a median age of
      18 years (2-37 years). Three patients were Mexican, 2 were white, and 1 was of
      Asian descent. All presented with fever, hepatosplenomegaly, and pancytopenia; 5
      were previously healthy, but had a clinical history of a recent viral-like upper
      respiratory illness (1 week to 2 months), and 1 patient had documented chronic
      active EBV infection for 7 years. Serologic data for EBV were incomplete but
      titers were either negative or only modestly elevated in 3 cases. In 1 case
      serology was consistent with severe chronic active EBV infection. In the
      remaining 2 cases serologic studies were not performed. All patients died within
      7 days to 8 months of presentation with T-cell LPD. On histologic examination,
      the liver and spleen showed prominent sinusoidal and portal lymphoid infiltrates
      of CD3(+), beta F1(+), EBER1(+) T cells lacking significant cytologic atypia. Two
      cases were CD4(+), 2 cases were CD8(+), and 2 cases had admixed CD4(+) and CD8(+)
      cells without clear subset predominance. All were TIA-1(+), CD56(-). Only rare B
      cells were noted. Marked erythrophagocytosis was present. Molecular analysis
      revealed identical T-cell clones in 2 or more sites (liver, spleen, lymph node)
      in 5 cases. All patients carried type A EBV; 4 cases had wild-type EBV-LMP, and 2
      showed the 30-bp deletion. This fulminant T-cell LPD after acute/chronic EBV
      infection is characterized by hepatosplenomegaly, often without significant
      lymphadenopathy, fever, liver failure, pancytopenia, and erythrophagocytosis
      indicative of a hemophagocytic syndrome. EBV serology may be misleading, with
      lack of elevated titers. The presence of an EBER1(+) T-cell infiltrate with scant
      B cells should alert one to this diagnosis. Although cytologic atypia is minimal,
      studies for T-cell clonality confirm the diagnosis. (Blood. 2000;96:443-451)

PMID- 10887105
TI  - A case-controlled study on the use of HBsAg-positive donors for allogeneic
      hematopoietic cell transplantation.
AB  - To compare the clinical and serological outcomes of patients receiving donors'
      marrow positive or negative for hepatitis B surface antigen (HBsAg), we studied
      18 patients of allogeneic hematopoietic cell transplantation receiving HBsAg
      positive marrow (group 1) and 18 receiving HBsAg-negative marrow (group 2). The
      recipients of the 2 groups were matched for hepatitis B virus (HBV) serology,
      sex, age, underlying hematological diseases, conditioning regimen, and
      prophylaxis against graft-versus-host diseases. Eight (44.4%) recipients in group
      1 and 2 (11.1%) in group 2 suffered from HBV-related hepatitis posttransplant (P
      =.03). Furthermore, HBV-related hepatic failure was seen in 6 group 1 patients,
      but in none of the group 2 patients (P =.007). Five of the 9 (55.5%) HBsAg
      negative recipients in group 1 became positive after receiving HBsAg-positive
      marrow. Serum HBV DNA was positive in all 5 donors of these patients, but in none
      of the donors of recipients who remained HBsAg negative (P =.008). Group 1
      patients developing HBV-related hepatitis posttransplant were more likely to have
      a donor carrying a precore A(1896 )and/or core promoter T(1762)/A(1764) HBV
      variant (62. 5% versus 0%, P =.007). This study has demonstrated that a high
      incidence of HBV-related hepatitis was associated with the use of HBsAg-positive
      marrow for transplant, and a high viral load in the donor appeared to predispose
      recipients to the development of HBV-related hepatitis posttransplant. Further
      clinical trials will be necessary to determine the optimal management approach to
      this problem, including the use of the antiviral agents in the donors and the
      recipients. (Blood. 2000;96:452-458)

PMID- 10887106
TI  - NFAT-controlled expression of GFP permits visualization and isolation of antigen
      stimulated primary human T cells.
AB  - We have developed a new method that allows detection and isolation of viable,
      antigen-specific, human T cells from a heterogeneous pool of T cells. We have
      engineered a self-inactivating retroviral vector containing multiple (3 or 6)
      nuclear factor of activated T-cell (NFAT)-binding sites, followed by the minimal
      IL2 promoter and the reporter gene GFP. Jurkat cells, primary T-cell blasts, and
      T-cell clones were transduced with high efficiency (20%-40%). Stimulation of the
      transduced cells with phorbol myristate acetate (PMA) and ionomycin resulted in a
      high level expression of GFP that was maximal after 12 to 14 hours and remained
      stable for another 12 hours. Activation of T cells carrying the construct
      containing 6 NFAT-binding sites resulted in the highest mean fluorescence
      intensity. Cyclosporin-A and FK506 were able to block the activation-dependent
      GFP expression. Activation of transduced T-cell blasts with the superantigen
      staphylococcal enterotoxin B or of transduced antigen-specific T-cell clones with
      cognate antigen resulted in GFP expression. After an overnight stimulation of a
      heterogeneous T-cell bulk culture with an HLA mismatched stimulator cell (JY),
      the GFP expressing cells were cloned. As expected, the cloning frequency of the
      antigen-specific GFP(+) cells was considerably higher than that of the total T
      cell population. Most of the T-cell clones were either cytolytic, or
      proliferative toward JY stimulator cells. Interestingly, we also isolated T-cell
      clones that were noncytolytic and nonproliferative toward JY cells, but
      specifically up-regulated GFP after an overnight stimulation with JY. (Blood.
      2000;96:459-466)

PMID- 10887107
TI  - Long-term in vivo survival of receptor-modified syngeneic T cells in patients
      with human immunodeficiency virus infection.
AB  - To study human immunodeficiency virus (HIV)-specific cellular immunity in vivo,
      we transferred syngeneic lymphocytes after ex vivo expansion and transduction
      with a chimeric receptor gene (CD4/CD3-zeta) between identical twins discordant
      for HIV infection. Single and multiple infusions of 10(10) genetically modified
      CD8(+) T cells resulted in peak fractions in the circulation of approximately
      10(4) to 10(5) modified cells/10(6) mononuclear cells at 24 to 48 hours, followed
      by 2- to 3-log declines by 8 weeks. In an effort to provide longer high-level
      persistence of the transferred cells and possibly enhance anti-HIV activity, we
      administered a second series of infusions in which both CD4(+ )and CD8(+) T cells
      were engineered to express the chimeric receptor and were costimulated ex vivo
      with beads coated with anti-CD3 and anti-CD28. Sustained fractions of
      approximately 10(3) to 10(4) modified cells/10(6) total CD4(+) or CD8(+) cells
      persisted for at least 1 year. Assessment of in vivo trafficking of the
      transferred cells by lymphoid tissue biopsies revealed the presence of modified
      cells in proportions equivalent to or below those in the circulation. The cell
      infusions were well tolerated and were not associated with substantive
      immunologic or virologic changes. Thus, adoptive transfer of genetically modified
      HIV-antigen-specific T cells was safe. Sustained survival in the circulation was
      achieved when modified CD4(+ )and CD8(+) T cells were infused together after ex
      vivo costimulation, indicating the important role played by antigen-specific
      CD4(+) T cells in providing "help" to cytotoxic effectors. (Blood. 2000;96:467
      474)

PMID- 10887108
TI  - Deregulated E2F-1 blocks terminal differentiation and loss of leukemogenicity of
      M1 myeloblastic leukemia cells without abrogating induction of p15(INK4B) and
      p16(INK4A).
AB  - The transcription factor E2F-1 has been postulated to play a crucial role in the
      control of cell cycle progression because of its ability to be bound and
      regulated by the retinoblastoma gene product (pRb). Exogenous expression of E2F
      1, under growth restrictive conditions, was shown to result in p53-dependent
      programmed cell death. The consequences of deregulated expression of E2F-1 on
      terminal differentiation of hematopoietic cells in the absence of E2F-1-mediated
      apoptosis, as well as mechanistic insights into how deregulated E2F-1 may affect
      terminal differentiation, have not been established. The autonomously
      proliferating M1 myeloblastic leukemia cell line, which is null for p53
      expression and can be induced by interleukin-6 (IL-6) to undergo terminal
      macrophage differentiation with concomitant loss of leukemogenicity, provides a
      particularly attractive model system to address these issues. Deregulated and
      continued expression of E2F-1 blocked the IL-6-induced terminal differentiation
      program at an early blast stage, giving rise to immature cells, which continued
      to proliferate without undergoing apoptosis and retained their leukemogenic
      phenotype. Although E2F-1 blocked IL-6-mediated terminal differentiation and its
      associated growth arrest, it did not prevent the rapid induction of both
      p15(INK4B) and p16(INK4A), inhibition of cdk4 kinase activity, and subsequent
      hypophosphorylation of pRb. The results obtained imply that genetic alterations
      that both impair p53 function and deregulate E2F-1 expression may render
      hematopoietic cells refractory to the induction of differentiation and are,
      thereby, likely to play a major role in the progression of leukemias. (Blood.
      2000;96:475-482)

PMID- 10887109
TI  - Myeloid specific human CD33 is an inhibitory receptor with differential ITIM
      function in recruiting the phosphatases SHP-1 and SHP-2.
AB  - CD33 is a myeloid specific member of the sialic acid-binding receptor family and
      is expressed highly on myeloid progenitor cells but at much lower levels in
      differentiated cells. Human CD33 has two tyrosine residues in its cytoplasmic
      domain (Y340 and Y358). When phosphorylated, these tyrosines could function as
      docking sites for the phosphatases, SHP-1 and/or SHP-2, enabling CD33 to function
      as an inhibitory receptor. Here we demonstrate that CD33 is tyrosine
      phosphorylated in the presence of the phosphatase inhibitor, pervanadate, and
      recruits SHP-1 and SHP-2. Co-expression studies suggest that the Src-family
      kinase Lck is effective at phosphorylating Y340, but not Y358, suggesting that
      these residues may function in the selective recruitment of adapter molecules and
      have distinct functions. Further support for overlapping, but nonredundant, roles
      for Y340 and Y358 comes from peptide-binding studies that revealed the
      recruitment of both SHP-1 and SHP-2 to Y340 but only SHP-2 to Y358. Analysis
      using mutants of SHP-1 demonstrated that binding Y340 of CD33 was primarily to
      the amino Src homology-2 domain of SHP-1. The potential of CD33 to function as an
      inhibitory receptor was demonstrated by its ability to down-regulate CD64-induced
      calcium mobilization in U937. The dependence of this inhibition on SHP-1 was
      demonstrated by blocking CD33-mediated effects with dominant negative SHP-1. This
      result implies that CD33 is an inhibitory receptor and also that SHP-1
      phosphatase has a significant role in mediating CD33 function. Further studies
      are essential to identify the receptor(s) that CD33 inhibits in vivo and its
      function in myeloid lineage development. (Blood. 2000;96:483-490)

PMID- 10887110
TI  - A new transacting factor that modulates hypoxia-induced expression of the
      erythropoietin gene.
AB  - Hypoxia is a strong stimulus for the transcription of a set of genes, including
      erythropoietin and vascular endothelial growth factor. Here we report on the
      cloning, functional significance, and expression of a complementary DNA (cDNA)
      that is involved in hypoxia-mediated expression of these 2 genes. The full-length
      cDNA encodes a predicted protein of 806 amino acids that contains a leucine
      zipper motif. This protein, termed HAF for hypoxia-associated factor, binds to a
      17-base pair (bp) region of the erythropoietin promoter, which was shown earlier
      to participate in hypoxia-induced expression of the erythropoietin gene. In Hep3B
      cells, clones modified to express HAF antisense RNA showed an attenuated response
      to hypoxia-mediated induction of both erythropoietin and vascular endothelial
      growth factor transcription. HAF showed sequence-specific interaction with a DNA
      element in the 5' untranslated region of VEGF gene. The HAF 2.6-kilobase (kb)
      messenger RNA (mRNA) is expressed in most adult tissues. The highest expression
      occurs in fetal liver and the least in adult liver. HAF is the murine homolog of
      Sart-1, a 125-kd human protein expressed in the nuclei of normal and malignant
      cells. (Blood. 2000;96:491-497)

PMID- 10887111
TI  - Connexin-43 gap junctions are involved in multiconnexin-expressing stromal
      support of hemopoietic progenitors and stem cells.
AB  - Gap junctions (GJs) provide for a unique system of intercellular communication
      (IC) allowing rapid transport of small molecules from cell to cell. GJs are
      formed by a large family of proteins named connexins (Cxs). Cx43 has been
      considered as the predominantly expressed Cx by hematopoietic-supporting stroma.
      To investigate the role of the Cx family in hemopoiesis, we analyzed the
      expression of 11 different Cx species in different stromal cell lines derived
      from murine bone marrow (BM) or fetal liver (FL). We found that up to 5 Cxs are
      expressed in FL stromal cells (Cx43, Cx45, Cx30.3, Cx31, and Cx31.1), whereas
      only Cx43, Cx45, and Cx31 were clearly detectable in BM stromal cells. In vivo,
      the Cx43-deficient 14.5- to 15-day FL cobblestone area-forming cells (CAFC)-week
      1-4 and colony-forming unit contents were 26%-38% and 39%-47% lower than in their
      wild-type counterparts, respectively. The reintroduction of the Cx43 gene into
      Cx43-deficient FL stromal cells was able to restore their diminished IC to the
      level of the wild-type FL stromal cells. In addition, these Cx43-reintroduced
      stromal cells showed an increased support ability (3.7-fold) for CAFC-week 1 in
      normal mouse BM and 5-fold higher supportive ability for CAFC-week 4 in 5
      fluorouracil-treated BM cells as compared with Cx43-deficient FL stromal cells.
      These findings suggest that stromal Cx43-mediated IC, although not responsible
      for all GJ-mediated IC of stromal cells, plays a role in the supportive ability
      for hemopoietic progenitors and stem cells. (Blood. 2000;96:498-505)

PMID- 10887112
TI  - VLA-4 (alpha(4)beta(1)) engagement defines a novel activation pathway for beta(2)
      integrin-dependent leukocyte adhesion involving the urokinase receptor.
AB  - During acute inflammatory processes, beta(2) and beta(1) integrins sequentially
      mediate leukocyte recruitment into extravascular tissues. We studied the
      influence of VLA-4 (very late antigen-4) (alpha(4)beta(1)) engagement on beta(2)
      integrin activation-dependent cell-to-cell adhesion. Ligation of VLA-4 by the
      soluble chimera fusion product vascular cell adhesion molecule-1 (VCAM-1)-Fc or
      by 2 anti-CD29 (beta(1) chain) monoclonal antibodies (mAb) rapidly induced
      adhesion of myelomonocytic cells (HL60, U937) to human umbilical vein endothelial
      cells (HUVECs). Cell adhesion was mediated via beta(2) integrin (LFA-1 and Mac-1)
      activation: induced adhesion to HUVECs was inhibited by blocking mAbs anti-CD18
      (70%-90%), anti-CD11a (50%-60%), or anti-CD11b (60%-70%). Adhesion to immobilized
      ligands of beta(2) integrins (intercellular adhesion molecule-1 [ICAM-1],
      fibrinogen, keyhole limpet hemocyanin) as well as to ICAM-1-transfected Chinese
      hamster ovary cells, but not to ligands of beta(1) integrins (VCAM-1,
      fibronectin, laminin, and collagen), was augmented. VCAM-1-Fc binding provoked
      the expression of the activation-dependent epitope CBRM1/5 of Mac-1 on
      leukocytes. Clustering of VLA-4 through dimeric VCAM-1-Fc was required for
      beta(2) integrin activation and induction of cell adhesion, whereas monovalent
      VCAM-1 or Fab fragments of anti-beta(1) integrin mAb were ineffective. Activation
      of beta(2) integrins by alpha(4)beta(1) integrin ligation (VCAM-1-Fc or anti
      beta(1) mAb) required the presence of urokinase receptor (uPAR) on leukocytic
      cells, because the removal of uPAR from the cell surface by phosphatidylinositol
      specific phospholipase C reduced cell adhesion to less than 40%. Adhesion was
      reconstituted when soluble recombinant uPAR was allowed to reassociate with the
      cells. Finally, VLA-4 engagement by VCAM-1-Fc or anti-beta(1) integrin mAb
      induced uPAR-dependent adhesion to immobilized vitronectin as well. These results
      elucidate a novel activation pathway of beta(2) integrin-dependent cell-to-cell
      adhesion that requires alpha(4)beta(1) integrin ligation for initiation and uPAR
      as activation transducer. (Blood. 2000;96:506-513)

PMID- 10887113
TI  - Different mechanisms define the antiadhesive function of high molecular weight
      kininogen in integrin- and urokinase receptor-dependent interactions.
AB  - Proteolytic cleavage of single-chain high molecular weight kininogen (HK) by
      kallikrein releases the short-lived vasodilator bradykinin and leaves behind 2
      chain high molecular weight kininogen (HKa) that has been previously reported to
      exert antiadhesive properties as well as to bind to the urokinase receptor (uPAR)
      on endothelial cells. In this study we defined the molecular mechanisms for the
      antiadhesive effects of HKa related to disruption of integrin- and uPAR-mediated
      cellular interactions. Vitronectin (VN) but not fibrinogen or fibronectin
      dependent alphavbeta(3) integrin-mediated adhesion of endothelial cells was
      blocked by HKa or its isolated domain 5. In a purified system, HKa but not HK
      competed for the interaction of VN with alphavbeta(3) integrin, because HKa and
      the isolated domain 5 but not HK bound to both multimeric and native VN in a
      Zn(2+)-dependent manner. The interaction between HKa or domain 5 with VN was
      prevented by heparin, plasminogen activator inhibitor-1, and a recombinant
      glutathione-S-transferase (GST)-fusion peptide GST-VN (1-77) consisting of the
      amino terminal portion of VN (amino acids 1-77), but not by a cyclic arginyl
      glycyl-aspartyl peptide, indicating that HKa interacts with the amino terminal
      portion of VN ("somatomedin B region"). Furthermore, we have confirmed that HKa
      but not HK bound to uPAR and to the truncated 2-domain form of uPAR lacking
      domain 1 in a Zn(2+)-dependent manner. Through these interactions, HKa or its
      recombinant His-Gly-Lys-rich domain 5 completely inhibited the uPAR-dependent
      adhesion of myelomonocytic U937 cells and uPAR-transfected BAF-3 cells to VN and
      thereby promoted cell detachment. By immunogold electron microscopy, both VN and
      HK/HKa were found to be colocalized in sections from human atherosclerotic
      coronary artery, indicating that the described interactions are likely to take
      place in vivo. Taken together, HK and HKa inhibit different VN-responsive
      adhesion receptor systems and may thereby influence endothelial cell- or
      leukocyte-related interactions in the vasculature, particularly under
      inflammatory conditions. (Blood. 2000;96:514-522)

PMID- 10887114
TI  - Deficient APC-cofactor activity of protein S Heerlen in degradation of factor Va
      Leiden: a possible mechanism of synergism between thrombophilic risk factors.
AB  - In protein S Heerlen, an S-to-P (single-letter amino acid codes) mutation at
      position 460 results in the loss of glycosylation of N458. This polymorphism has
      been found to be slightly more prevalent in thrombophilic populations than in
      normal controls, particularly in cohorts of patients having free protein S
      deficiency. This suggests that carriers of the Heerlen allele may have an
      increased risk of thrombosis. We have now characterized the expression in cell
      cultures of recombinant protein S Heerlen and investigated the anticoagulant
      functions of the purified recombinant protein in vitro. Protein S Heerlen was
      synthesized and secreted equally well as wild-type protein S by transiently
      transfected COS-1 cells. The recombinant protein S Heerlen interacted with
      conformation-dependent monoclonal antibodies and bound C4b-binding protein to the
      same extent as wild-type protein S. Protein S Heerlen displayed reduced
      anticoagulant activity as cofactor to activated protein C (APC) in plasma-based
      assays, as well as in a factor VIIIa-degradation system. In contrast, protein S
      Heerlen functioned equally well as an APC cofactor in the degradation of factor
      Va as wild-type protein S did. However, when recombinant activated factor V
      Leiden (FVa:Q506) was used as APC substrate, protein S Heerlen was found to be a
      poor APC cofactor as compared with wild-type protein S. These in vitro results
      suggest a possible mechanism of synergy between protein S Heerlen and factor V
      Leiden that might be involved in the pathogenesis of thrombosis in individuals
      carrying both genetic traits. (Blood. 2000;96:523-531)

PMID- 10887115
TI  - Surface expression of glycoprotein ib alpha is dependent on glycoprotein ib beta:
      evidence from a novel mutation causing Bernard-Soulier syndrome.
AB  - Bernard-Soulier syndrome is a rare bleeding disorder caused by a quantitative or
      qualitative defect in the platelet glycoprotein (GP) Ib-IX-V complex. The
      complex, which serves as a platelet receptor for von Willebrand factor, is
      composed of 4 subunits: GPIb alpha, GPIb beta, GPIX, and GPV. We here describe
      the molecular basis of a novel form of Bernard-Soulier syndrome in a patient in
      whom the components of the GPIb-IX-V complex were undetectable on the platelet
      surface. Although confocal imaging confirmed that GPIb alpha was not present on
      the platelet surface, GPIb alpha was readily detectable in the patient's
      platelets. Moreover, immunoprecipitation of plasma with specific monoclonal
      antibodies identified circulating, soluble GPIb alpha. DNA-sequence analysis
      revealed normal sequences for GPIb alpha and GPIX. There was a G to A
      substitution at position 159 of the gene encoding GPIb beta, resulting in a
      premature termination of translation at amino acid 21. Studies of transient
      coexpression of this mutant, W21stop-GPIb beta, together with wild-type GPIbalpha
      and GPIX, demonstrated a failure of GPIX expression on the surface of HEK 293T
      cells. Similar results were obtained with Chinese hamster ovary alpha IX cells, a
      stable cell line expressing GPIbalpha that retains the capacity to re-express
      GPIX. Thus, we found that GPIbbeta affects the surface expression of the GPIb-IX
      complex by failing to support the insertion of GPIb alpha and GPIX into the
      platelet membrane. (Blood. 2000;96:532-539)

PMID- 10887116
TI  - Molecular analysis of human anti-factor VIII antibodies by V gene phage display
      identifies a new epitope in the acidic region following the A2 domain.
AB  - One of the major binding sites for factor VIII inhibitors is located within the
      A2 domain. In this study, phage display technology was used to isolate 2 human
      monoclonal antibodies, termed VK34 and VK41, directed toward the heavy chain of
      factor VIII. The V(H) domain of a single-chain variable domain antibody fragment
      (scFv) VK34 is encoded by germline gene segment DP-10. Epitope-mapping studies
      revealed that scFv VK34 is directed against amino acid residues Arg(484)
      Ile(508), a previously identified binding site for factor VIII inhibitors in the
      A2 domain. ScFv VK34 inhibited factor VIII activity with a titer of 280 BU/mg.
      The V(H) domain of VK41 was encoded by germline gene segment DP-47. A phage
      corresponding to VK41 competed with a monoclonal antibody for binding to amino
      acid residues Asp(712)-Ala(736) in the acidic region adjacent to the A2 domain.
      Reactivity of VK41 with a factor VIII variant in which we replaced amino acid
      residues Asp(712)-Ala(736) for the corresponding region of heparin cofactor II
      was strongly reduced. In addition, substitution of Tyr(718719723) for Phe
      abrogated binding of VK41 to factor VIII. ScFv VK41 did not inhibit factor VIII
      activity. This study not only defines the primary structure of human anti-factor
      VIII antibodies reactive with the A2 domain, it also describes an antibody with
      an epitope not previously identified in the antibody repertoire of hemophilia
      patients with an inhibitor. (Blood. 2000;96:540-545)

PMID- 10887117
TI  - Involvement of vascular endothelial growth factor receptor-3 in maintenance of
      integrity of endothelial cell lining during tumor angiogenesis.
AB  - Vascular endothelial growth factor (VEGF) plays a major role in tumor
      angiogenesis. VEGF-C, however, is thought to stimulate the growth of lymphatic
      vessels because an expression of its specific receptor, VEGF receptor-3 (VEGFR
      3), was demonstrated to be restricted to lymphatic vessels. Here we demonstrate
      that the inactivation of VEGFR-3 by a novel blocking monoclonal antibody (mAb)
      suppresses tumor growth by inhibiting the neo-angiogenesis of tumor-bearing
      tissues. Although VEGFR-3 is not expressed in adult blood vessels, it is induced
      in vascular endothelial cells of the tumor-bearing tissues. Hence, VEGFR-3 is
      another receptor tyrosine kinase involved in tumor-induced angiogenesis. Micro
      hemorrhage in the tumor-bearing tissue was the most conspicuous histologic
      finding specific to AFL4 mAb-treated mice. Scanning microscopy demonstrated
      disruptions of the endothelial lining of the postcapillary venule, probably the
      cause of micro-hemorrhage and the subsequent collapse of the proximal vessels.
      These findings suggest the involvement of VEGFR-3 in maintaining the integrity of
      the endothelial lining during angiogenesis. Moreover, our results suggest that
      the VEGF-C/VEGFR-3 pathway may serve another candidate target for cancer therapy.
      (Blood. 2000;96:546-553)

PMID- 10887118
TI  - The in vivo kinetics of tissue factor messenger RNA expression during human
      endotoxemia: relationship with activation of coagulation.
AB  - Triggering of the tissue factor (TF)-dependent coagulation pathway is considered
      to underlie the generation of a procoagulant state during endotoxemia. To
      determine the in vivo pattern of monocytic TF messenger RNA (mRNA) expression
      during endotoxemia, 10 healthy volunteers were injected with lipopolysaccharide
      (LPS, 4 ng/kg) and blood was collected before and 0.5, 1, 2, 3, 4, 6, 8, and 24
      hours after LPS administration. Total blood RNA was isolated and amplified by
      NASBA (nucleic acid sequence-based amplification), followed by quantitation of TF
      mRNA by an electrochemiluminescence (ECL) assay. To compare the pattern of
      coagulation activation with the kinetics of monocytic TF mRNA expression, we
      measured plasma levels of markers of thrombin generation, thrombin-antithrombin
      (TAT) complexes, and prothrombin fragment 1 + 2 (F1 + 2). Baseline value (mean +/
      SEM) of the number of TF mRNA molecules per monocytic cell was 0.08 +/- 0.02. A
      progressive and significant (P <.0001) increase in TF expression was observed
      after LPS injection (+0.5 hour: 0.3 +/- 0.1, +1 hour: 1.3 +/- 0.9, +2 hours: 4.1
      +/- 0.9), peaking at +3 hours (10 +/- 1.9 TF mRNA molecules per monocyte). As TF
      mRNA levels increased, thrombin generation was augmented. Peak levels of TAT and
      F1 + 2 were reached later (at t +4 hours) than those of TF mRNA. TF mRNA, TAT,
      and F1 + 2 levels returned to baseline after 24 hours. In conclusion, we used a
      NASBA/ECL-based technique to quantify TF mRNA in whole blood during human
      endotoxemia and observed a 125-fold increase in TF mRNA levels. Our data
      demonstrate a pivotal role for enhanced TF gene activity in the activation of
      coagulation after LPS challenge. (Blood. 2000;96:554-559)

PMID- 10887119
TI  - A novel von Willebrand disease-causing mutation (Arg273Trp) in the von Willebrand
      factor propeptide that results in defective multimerization and secretion.
AB  - In this report we describe the molecular defect underlying partial and severe
      quantitative von Willebrand factor (VWF) deficiencies in 3 families previously
      diagnosed with types 1 and 3 Von Willebrand-disease. Analysis of the VWF gene in
      affected family members revealed a novel C to T transition at nucleotide 1067 of
      the VWF complemetary DNA (cDNA), predicting substitution of arginine by
      tryptophan at amino acid position 273 (R273W) of pre-pro-VWF. Two patients,
      homozygous for the R273W mutation, had a partial VWF deficiency (VWF:Ag levels of
      0.06 IU/mL and 0.09 IU/mL) and lacked high-molecular weight VWF multimers in
      plasma. A third patient, also homozygous for the R273W mutation, had a severe VWF
      deficiency (VWF:Ag level of less than 0.01 IU/mL) and undetectable VWF multimers
      in plasma. Recombinant VWF having the R273W mutation was expressed in COS-7
      cells. Pulse-chase experiments showed that secretion of rVWFR273W was severely
      impaired compared with wild-type rVWF. However, the mutation did not affect the
      ability of VWF to form dimers in the endoplasmic reticulum (ER). Multimer
      analysis showed that rVWFR273W failed to form high-molecular-weight multimers
      present in wild-type rVWF. We concluded that the R273W mutation is responsible
      for the quantitative VWF deficiencies and aberrant multimer patterns observed in
      the affected family members. To identify factors that may function in the
      intracellular retention of rVWFR273W, we investigated the interactions of VWF
      expressed in COS-7 cells with molecular chaperones of the ER. The R273W mutation
      did not affect the ability of VWF to bind to BiP, Grp94, ERp72, calnexin, and
      calreticulin in COS-7 cells. (Blood. 2000;96:560-568)

PMID- 10887120
TI  - Neuroserpin reduces cerebral infarct volume and protects neurons from ischemia
      induced apoptosis.
AB  - Neuroserpin, a recently identified inhibitor of tissue-type plasminogen activator
      (tPA), is primarily localized to neurons within the central nervous system, where
      it is thought to regulate tPA activity. In the present study neuroserpin
      expression and its potential therapeutic benefits were examined in a rat model of
      stroke. Neuroserpin expression increased in neurons surrounding the ischemic core
      (ischemic penumbra) within 6 hours of occlusion of the middle cerebral artery and
      remained elevated during the first week after the ischemic insult. Injection of
      neuroserpin directly into the brain immediately after infarct reduced stroke
      volume by 64% at 72 hours compared with control animals. In untreated animals
      both tPA and urokinase-type plasminogen activator (uPA) activity was
      significantly increased within the region of infarct by 6 hours after
      reperfusion. Activity of tPA then decreased to control levels by 72 hours,
      whereas uPA activity continued to rise and was dramatically increased by 72
      hours. Both tPA and uPA activity were significantly reduced in neuroserpin
      treated animals. Immunohistochemical staining of basement membrane laminin with a
      monoclonal antibody directed toward a cryptic epitope suggested that proteolysis
      of the basement membrane occurred as early as 10 minutes after reperfusion and
      that intracerebral administration of neuroserpin significantly reduced this
      proteolysis. Neuroserpin also decreased apoptotic cell counts in the ischemic
      penumbra by more than 50%. Thus, neuroserpin may be a naturally occurring
      neuroprotective proteinase inhibitor, whose therapeutic administration decreases
      stroke volume most likely by inhibiting proteinase activity and subsequent
      apoptosis associated with focal cerebral ischemia/reperfusion. (Blood.
      2000;96:569-576)

PMID- 10887121
TI  - Phosphoinositide 3-kinase forms a complex with platelet membrane glycoprotein Ib
      IX-V complex and 14-3-3zeta.
AB  - The binding of von Willebrand factor (vWF) to glycoprotein (GP) Ib-IX-V
      stimulates transmembrane signaling events that lead to platelet adhesion and
      aggregation. Recent studies have revealed that the signaling protein 14-3-3 zeta
      binds directly to the cytoplasmic domain of GP Ib alpha. In this study, the
      dynamic association of 14-3-3 zeta with GP Ib-IX, the phosphoinositide 3-kinase
      (PI 3-kinase), or both, was investigated in resting, thrombin, or vWF and
      botrocetin-stimulated platelets by analysis of discrete subcellular fractions.
      Results of this study demonstrate maximal coimmunoprecipitation of 14-3-3 zeta
      with GP Ib-IX in the nonstimulated cytosolic fraction and in the actin
      cytoskeletal fraction of thrombin- or vWF-stimulated human platelets.
      Immunoprecipitated 14-3-3 zeta or GP Ib from cytosolic fractions contained PI 3
      kinase enzyme activity and an 85-kd polypeptide recognized by antibodies to the
      p85 subunit of PI 3-kinase. After platelet activation, the level of association
      between these species decreased in the cytosolic fraction. However, increased
      complex formation between 14-3-3 zeta and GP Ib-IX and between PI 3-kinase and GP
      Ib-IX was detected in actin cytoskeletal fractions derived from thrombin- or vWF
      stimulated platelets. Recombinant glutathione S-transferase-14-3-3 zeta fusion
      protein (14-3-3 zeta-GST) inhibited affinity-captured PI 3-kinase enzyme activity
      up to 70% at 2 mcmol/L 14-3-3 zeta-GST. However, increasing concentrations up to
      5 mcmol/L 14-3-3 zeta-GST resulted in the 3-fold enhancement of PI 3-kinase
      enzyme activity. We propose that the association between PI 3-kinase and 14-3-3
      zeta with GP Ib-IX serves to promote the rapid translocation of these signaling
      proteins to the activated cytoskeleton, thereby regulating the formation of 3
      position phosphoinositide-signaling molecules in this subcellular compartment.
      (Blood. 2000;96:577-584)

PMID- 10887122
TI  - The autolysis loop of activated protein C interacts with factor Va and
      differentiates between the Arg506 and Arg306 cleavage sites.
AB  - The anticoagulant human plasma serine protease, activated protein C (APC),
      inactivates blood coagulation factors Va (FVa) and VIIIa. The so-called autolysis
      loop of APC (residues 301-316, equivalent to chymotrypsin [CHT] residues 142-153)
      has been hypothesized to bind FVa. In this study, site-directed mutagenesis was
      used to probe the role of the charged residues in this loop in interactions
      between APC and FVa. Residues Arg306 (147 CHT), Glu307, Lys308, Glu309, Lys311,
      Arg312, and Arg314 were each individually, or in selected combinations, mutated
      to Ala. The purified recombinant protein C mutants were characterized using
      activated partial thromboplastin time (APTT) clotting assays and FVa inactivation
      assays. Mutants 306A, 308A, 311A, 312A, and 314A had mildly reduced anticoagulant
      activity. Based on FVa inactivation assays and APTT assays using purified Gln506
      FVa and plasma containing Gln506-FV, it appeared that these mutants were
      primarily impaired for cleavage of FVa at Arg506. Studies of the quadruple APC
      mutant (306A, 311A, 312A, and 314A) suggested that the autolysis loop provides
      for up to 15-fold discrimination of the Arg506 cleavage site relative to the
      Arg306 cleavage site. This study shows that the loop on APC of residues 306 to
      314 defines an FVa binding site and accounts for much of the difference in
      cleavage rates at the 2 major cleavage sites in FVa. (Blood. 2000;96:585-593)

PMID- 10887123
TI  - Impaired binding of perforin on the surface of tumor cells is a cause of target
      cell resistance against cytotoxic effector cells.
AB  - Exocytosis of perforin, subsequent binding of perforin to the target cell
      membrane, and formation of lytic pores form an important pathway involved in the
      induction of tumor cell death by cytotoxic effector cells. Here we describe a
      novel escape mechanism employed by tumor cells to protect themselves from granule
      mediated cell death: We were able to demonstrate that the resistance of the human
      leukemia cell line ML-2 to natural killer (NK)-cell-mediated killing is not
      caused by impaired NK-cell activation but by resistance against effector
      molecules contained in the granules of cytotoxic cells. No resistance was
      observed against other pore-forming agents like complement and streptolysin O. By
      using the NK-susceptible leukemia cell line K562, we could show that the
      induction of cell death by cytotoxic granules can be blocked completely by anti
      perforin antibodies, indicating that perforin is essentially involved in this
      process. Flow cytometric data revealed that an impaired binding of perforin on
      the tumor cell membrane is mainly responsible for target cell resistance, because
      perforin turned out to bind well on K562 cells but is not able to attach to the
      surface of ML-2 cells. After impaired binding of perforin was identified as a
      potential mechanism of tumor cell resistance, leukemia cells from 6 patients with
      acute myeloid leukemia (AML) were examined. As predicted, AML cells that failed
      to bind perforin on their surface demonstrated complete resistance toward NK-cell
      mediated cytotoxicity. Thus, perforin resistance could represent an important
      tumor escape mechanism that should be considered when cytotoxic effector cells
      are used for cellular immunotherapy. (Blood. 2000;96:594-600)

PMID- 10887124
TI  - New induction of leukotriene A(4) hydrolase by interleukin-4 and interleukin-13
      in human polymorphonuclear leukocytes.
AB  - Interleukin (IL)-4, IL-10, and IL-13, Th2 cell-derived cytokines, play major
      roles in the pathophysiology of allergic diseases. These cytokines up-regulate or
      down-regulate the production of arachidonic acid metabolites. In this study, we
      have investigated the effect of IL-4, IL-10, IL-13, and other cytokines on A23187
      stimulated synthesis of leukotriene (LT) B(4) in human polymorphonuclear
      leukocytes (PMNs). Production of LTB(4) was measured by specific radioimmunoassay
      and high performance liquid chromatography. Messenger RNA (mRNA) expression of
      cytosolic phospholipase A(2) (cPLA(2)), 5-lipoxygenase (5-LO), and LTA(4)
      hydrolase, which were involved in the synthesis of LTB(4), was determined by
      reverse transcription-polymerase chain reaction and Northern blot analysis.
      Protein synthesis of their enzymes was determined by Western blot analysis. IL-4
      and IL-13 enhanced A23187-stimulated LTB(4) synthesis and increased mRNA
      expression and protein synthesis of LTA(4) hydrolase, but not those of cPLA(2) or
      5-LO. These results indicate that IL-4 and IL-13 transcriptionally or post
      transcriptionally up-regulate the synthesis of LTB(4), a potent chemotactic
      factor to PMNs, at the enzyme level of LTA(4) hydrolase, and this up-regulation
      mechanism may participate in the development of allergic inflammation. (Blood.
      2000;96:601-609)

PMID- 10887125
TI  - Genetic defect in human X-linked agammaglobulinemia impedes a maturational
      evolution of pro-B cells into a later stage of pre-B cells in the B-cell
      differentiation pathway.
AB  - Surrogate light chains (lambda 5/VpreB) are selectively expressed in early
      precursors of B cells. B-cell defects in X-linked agammaglobulinemia (XLA) are
      caused by mutations in the gene for Bruton's tyrosine kinase. To elucidate the
      nature of early B-lineage cells in bone marrow (BM), samples from 13 XLA patients
      and 24 healthy controls of different ages were comparatively analyzed using an
      antihuman VpreB monoclonal antibody. Expression of surrogate light (SL) and mu
      heavy chains were examined after cell membrane permeabilization because they are
      mainly expressed in the cytoplasm of early B-lineage cells. A flow cytometric
      analysis of normal BM identified 5 discrete cell types of B cells: mu(-)SL(++)
      (pro-B [B-cell progenitor]), mu(low)SL(++) (pre-B1a), mu(low)SL(+) (pre-B1b),
      mu(low)SL(- )(pre-B2), and mu(high)SL(- )(B). The large cells, presumably in
      cycling states, were enriched in pre-B1a cells. The frequencies of B-lineage
      cells in BM were higher in young children, and declined with advancing age. In
      contrast, XLA showed a profound reduction in BM B-lineage cells. In XLA BM, an
      expansion of pro-B cells with some small pre-B1a cells was marked, but other
      cells were negligible. These observations illustrate a B-cell maturation defect
      in XLA as well as a normal human B-cell differentiation pathway. The results
      suggest that the genetic defect in XLA may impede the evolution of pro-B cells
      beyond the earlier pre-B stage into the later stage of pre-B cells in B-cell
      development. (Blood. 2000;96:610-617)

PMID- 10887126
TI  - Characterization of Ggrb4, an adapter protein interacting with Bcr-Abl.
AB  - We report here the characterization of an adapter protein identified in a yeast 2
      hybrid screen with the use of Bcr-Abl as the bait. Grb4 bound to Bcr-Abl in a
      variety of systems, both in vitro and in vivo, and is an excellent substrate of
      the Bcr-Abl tyrosine kinase. The association of Grb4 and Bcr-Abl in intact cells
      was mediated by an src homology (SH)2-mediated phosphotyrosine-dependent
      interaction as well as an SH3-mediated phosphotyrosine-independent interaction.
      Grb4 has 68% homology to the adapter protein Nck and has similar but distinct
      binding specificities in K562 lysates. Subcellular localization studies indicate
      that Grb4 localizes to both the nucleus and the cytoplasm. Coexpression of kinase
      active Bcr-Abl with Grb4 resulted in the translocation of Grb4 from the cytoplasm
      and the nucleus to the cytoskeleton to colocalize with Bcr-Abl. In addition,
      expression of Grb4 with kinase-active Bcr-Abl resulted in a redistribution of
      actin-associated Bcr-Abl. Finally, coexpression of Grb4 and oncogenic v-Abl
      strongly inhibited v-Abl-induced AP-1 activation. Together, these data indicate
      that Grb4 in conjunction with Bcr-Abl may be capable of modulating the
      cytoskeletal structure and negatively interfering with the signaling of oncogenic
      Abl kinases. Grb4 may therefore play a role in the molecular pathogenesis of
      chronic myelogenous leukemia. (Blood. 2000;96:618-624) (Blood. 2000;96:618-624)

PMID- 10887127
TI  - Stable expression of Epstein-Barr virus BZLF-1-encoded ZEBRA protein activates
      p53-dependent transcription in human Jurkat T-lymphoblastoid cells.
AB  - Interaction between viral proteins and tumor suppressor p53 is a common mechanism
      of viral pathogenesis. The Epstein-Barr virus (EBV) BZLF-1 ORF-encoded ZEBRA
      protein (also denoted EB1, Z, Zta) binds to p53 in vitro and has been associated
      with the altered transcription of p53-regulated genes in B lymphocytes and
      epithelial cells. In this work, Jurkat T-lymphoblastoid cells that express ZEBRA
      were characterized by the use of transiently transfected p53 and p53 reporter
      genes. Stable expression of ZEBRA was associated with the activation of p53
      dependent transcription and increased p53 dependent apoptotic cell death. In
      Jurkat cell lines, stably expressed ZEBRA protein was apparently localized to the
      cell cytoplasm, in contrast to the typical nuclear localization of this protein
      in other cell types. Previous studies have suggested that EBV infection of T
      lymphocytes may contribute to the malignant transformation of T cells and the
      increased replication of human immunodeficiency virus. Our observations suggest a
      mechanism through which ZEBRA protein expressed in human T lymphocytes could
      alter T-cell proliferation and apoptosis during EBV infection. (Blood.
      2000;96:625-634)

PMID- 10887128
TI  - Higher-grade transformation of follicle center lymphoma is associated with
      somatic mutation of the 5' noncoding regulatory region of the BCL-6 gene.
AB  - Follicle center lymphoma (FCL) is an indolent low-grade B-cell non-Hodgkin's
      lymphoma (NHL) that frequently transforms to aggressive diffuse large B-cell
      lymphoma (DLBCL). Histologic transformation of FCL is commonly associated with
      accumulation of secondary genetic alterations. The BCL-6 gene is altered by
      chromosomal rearrangements and mutations clustering in its 5' noncoding
      regulatory region in up to 70% of primary DLBCL, but in a significantly smaller
      subset of FCL. Previous studies have shown that both chromosomal rearrangements
      and mutations could deregulate BCL-6 expression. To evaluate the association
      between progressive accumulation of BCL-6 regulatory region mutations and the
      histologic transformation of FCL, we analyzed by extensive cloning and sequencing
      paired biopsy specimens obtained at the time of FCL diagnosis and transformation
      (6 patients) or FCL relapse (3 patients). In an additional patient, biopsy
      specimens obtained at the time of diagnosis, FCL relapse, and subsequent
      transformation to DLBCL were evaluated. The presence of identical mutations in
      the paired diagnosis and posttransformation DLBCL specimens confirmed the common
      clonal origin of both the pretransformation and the posttransformation lymphomas.
      No new mutations in the 5' noncoding regulatory region of the BCL-6 gene were
      detected in any of the specimens evaluated at the time of FCL relapse. In
      contrast, 5 of the 7 transformed specimens contained new mutations not found in
      the paired original biopsy specimens obtained at the time of FCL diagnosis or
      relapse. The number of these new mutations ranged from 1 to 6 per specimen. Some
      of the new mutations tended to cluster in certain areas of the 5' noncoding
      regulatory region of the BCL-6 gene. Our results show that transformation of FCL
      to DLBCL is associated with accumulation of new mutations in the 5' noncoding
      regulatory region of the BCL-6 gene, that by deregulation of the BCL-6 gene
      expression may play a role in lymphoma transformation. (Blood. 2000;96:635-639)

PMID- 10887129
TI  - High detection rate of T-cell receptor beta chain rearrangements in T-cell
      lymphoproliferations by family specific polymerase chain reaction in combination
      with the GeneScan technique and DNA sequencing.
AB  - The distinction between benign polyclonal and malignant monoclonal lymphoid
      disorders by morphology or immunophenotyping is frequently difficult. Therefore,
      the demonstration of clonal B-cell or T-cell populations by detecting identically
      rearranged immunoglobulin (Ig) or T-cell receptor (TCR) genes is often used to
      solve this diagnostic problem. Whereas the detection of rearranged Ig genes is
      well established, TCR gamma (gamma) and beta (beta) gene rearrangements often
      escape detection with the currently available polymerase chain reaction (PCR)
      assays. To establish a sensitive, specific, and rapid method for the detection of
      rearranged TCR-beta genes, we developed a new PCR approach with family-specific
      Jbeta primers and analyzed the resulting PCR products by high-resolution GeneScan
      technique. The superior efficiency of this new method was demonstrated by
      investigating 132 DNA samples extracted from lymph node and skin biopsy specimens
      (mostly formalin fixed) and blood samples of 62 patients who had a variety of T
      cell lymphomas and leukemias. In all but 1 of the tumor samples (98.4%) a clonal
      amplificate was detectable after TCR-beta PCR and the same clonal T-cell
      population was also found in 15 of 18 (83%) of the regional lymph nodes and in 7
      of 11 (64%) of the peripheral blood samples. Direct comparison of these results
      with those obtained currently by the most widely applied TCR-gamma PCR revealed
      an approximate 20% lower detection rate in the same set of samples than with the
      TCR-beta PCR method. These results indicate that the new TCR-beta PCR is most
      suitable for a rapid and reliable detection of clonal T-cell populations. (Blood.
      2000;96:640-646)

PMID- 10887130
TI  - Analysis of TNF-receptor and ligand superfamily molecules in patients with
      lymphoproliferative disease of granular lymphocytes.
AB  - In 21 patients with lymphoproliferative disease of granular lymphocytes (LDGL),
      we investigated the expression and the function of molecules belonging to TNF
      receptor and TNF-ligand superfamilies (CD30/CD30L; CD40/CD40L; CD27/CD70; Fas
      [CD95]/FasL[CD95L]). Fourteen patients were characterized by a proliferation of
      granular lymphocytes (GLs) expressing the CD3(+)CD16(+) phenotype, whereas 7
      cases showed the CD3(-)CD16(+) CD56 +/- phenotype. Our data show that both CD3(+)
      and CD3-GLs are preferentially equipped with CD30, CD40, CD40L, CD70, and CD95
      antigens; this pattern is usually associated with the lack of CD27 and CD30L
      antigens expression. CD95L was demonstrated in the cytoplasm in 14 of 21 cases by
      flow cytometry, but a definite signal was demonstrated in all cases studied using
      polymerase chain reaction analysis. On functional grounds, a stimulatory activity
      on rIL-2 mediated redirected-cytotoxicity against Fcgamma+ P815 targets was
      demonstrated with anti-CD30, CD40, CD40L, CD70, CD95, and CD95L mAbs, although
      resting cells were unable to exhibit significant redirected-cell lysis. The
      addition of anti-CD30, CD30L, CD40, CD40L, CD95, and CD95L mAbs did not show any
      significant effect on cell proliferation at resting conditions or after rIL-2
      stimulation, whereas anti-CD70 mAb mediated cell proliferation in 6 of 10 cases
      tested. This figure was not related to an increase in apoptotic cells, as
      investigated by Annexin-V expression. Our data indicate that both CD3(+) and CD3(
      ) GLs are equipped with different costimulatory antigens, supporting the concept
      that these cells are in vivo activated and suggesting that these molecules might
      play a role in the cytotoxic mechanisms of GLs. (Blood. 2000;96:647-654)

PMID- 10887131
TI  - Analysis of genes under the downstream control of the t(8;21) fusion protein AML1
      MTG8: overexpression of the TIS11b (ERF-1, cMG1) gene induces myeloid cell
      proliferation in response to G-CSF.
AB  - The AML1-MTG8 fusion transcription factor generated by t(8;21) translocation is
      thought to dysregulate genes that are crucial for normal differentiation and
      proliferation of hematopoietic progenitors to cause acute myelogenous leukemia
      (AML). Although AML1-MTG8 has been shown to repress the transcription of AML1
      targets, none of the known targets of AML1 are probably responsible for AML1-MTG8
      mediated leukemogenesis. In this study, 24 genes under the downstream control of
      AML1-MTG8 were isolated by using a differential display technique. Analysis with
      deletion mutants of AML1-MTG8 demonstrated that the regulation of the majority of
      these genes requires the region of 51 residues (488-538) containing the Nervy
      homology region 2 (NHR2), through which AML1-MTG8 interacts with MTGR1. Among the
      24 genes identified, 10 were considered to be genes under the control of AML1,
      because their expression was altered by AML1b or AML1a or both. However, the
      other 14 genes were not affected by either AML1b or AML1a, suggesting the
      possibility that AML1-MTG8 regulates a number of specific target genes that are
      not normally regulated by AML1. Furthermore, an up-regulated gene, TIS11b (ERF-1,
      cMG1), was highly expressed in t(8;21) leukemic cells, and the overexpression of
      TIS11b induced myeloid cell proliferation in response to granulocyte colony
      stimulating factor. These results suggest that the high-level expression of
      TIS11b contributes to AML1-MTG8-mediated leukemogenesis. (Blood. 2000;96:655-663)

PMID- 10887132
TI  - The Grb2 binding site is required for the induction of chronic myeloid leukemia
      like disease in mice by the Bcr/Abl tyrosine kinase.
AB  - The BCR/ABL oncogene results from a balanced translocation between chromosomes 9
      and 22 and is found in patients with chronic myeloid leukemia (CML) and in some
      patients with acute B-lymphoid leukemia. The Bcr/Abl fusion protein is a
      constitutively active tyrosine kinase that stimulates several intracellular
      signaling pathways, including activation of Ras through direct binding of the SH2
      containing adapter protein Grb2 to Bcr tyrosine 177. A tyrosine-to-phenylalanine
      mutation (Y177F) at this site blocks the co-association of Bcr/Abl and Grb2 in
      vivo and impairs focus formation by Bcr/Abl in fibroblasts. However, the Bcr/Abl
      Y177F mutant can transform hematopoietic cell lines and primary bone marrow cells
      in vitro, so the importance of the Bcr/Abl-Grb2 interaction to myeloid and
      lymphoid leukemogenesis in vivo is unclear. We have recently demonstrated the
      efficient induction of CML-like myeloproliferative disease by BCR/ABL in a murine
      bone marrow transduction/transplantation model system. The Y177F mutation greatly
      attenuates the myeloproliferative disease induced by BCR/ABL, with mice
      developing B- and T-lymphoid leukemias of longer latency. In addition, the v-abl
      oncogene of Abelson murine leukemia virus, whose protein product lacks
      interaction with Grb2, is completely defective for the induction of CML-like
      disease. These results suggest that direct binding of Grb2 is required for the
      efficient induction of CML-like myeloproliferative disease by oncogenic Abl
      proteins. (Blood. 2000;96:664-670)

PMID- 10887133
TI  - Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory
      factor in multiple myeloma.
AB  - This study was designed to determine if macrophage inhibitory protein-1 alpha
      (MIP-1 alpha), a recently described osteoclast (OCL) stimulatory factor,(1) was
      present in marrow from patients with multiple myeloma (MM) and possibly involved
      in the bone destructive process. MIP-1 alpha, but not interleukin-1 beta (IL-1
      beta), tumor necrosis factor-beta (TNF-beta), or interleukin-6 (IL-6), messenger
      RNA was elevated in freshly isolated bone marrow from 3 of 4 patients with MM
      compared to normal controls. Furthermore, enzyme-linked immunosorbent assays of
      freshly isolated bone marrow plasma detected increased concentrations of hMIP-1
      alpha (range, 75-7784 pg/mL) in 8 of 13 patients (62%) with active myeloma, in 3
      of 18 patients (17%) with stable myeloma (range, 75-190.3), as well as in
      conditioned media from 4 of 5 lymphoblastoid cell lines (LCLs) derived from
      patients with MM. Mildly elevated levels of MIP-1 alpha were detected in 3 of 14
      patients (21%) with other hematologic diagnoses (range, 80.2-118.3, median value
      of 96 pg/mL) but not in normal controls (0 of 7). MIP-1 alpha was not detected in
      the peripheral blood of any patients with MM. In addition, recombinant hMIP-1
      alpha induced OCL formation in human bone marrow cultures. Importantly, addition
      of a neutralizing antibody to MIP-1 alpha to human bone marrow cultures treated
      with freshly isolated marrow plasma from patients with MM blocked the increased
      OCL formation induced by these marrow samples but had no effect on control levels
      of OCL formation. Thus, high levels of MIP-1 alpha are expressed in marrow
      samples from patients with MM, but not in marrow from patients with other
      hematologic disorders or controls, and support an important role for MIP-1 alpha
      as one of the major factors responsible for the increased OCL stimulatory
      activity in patients with active MM. (Blood. 2000;96:671-675)

PMID- 10887134
TI  - Versatility of BCR/ABL-expressing leukemic cells in circumventing proapoptotic
      BAD effects.
AB  - BAD, the proapoptotic member of the "BH3-only" subfamily of BCL-2 proteins, is
      inactivated by phosphorylation at serines 112 and 136 and by sequestration in the
      cytoplasm where it interacts with members of the 14-3-3 family. In BCR/ABL
      expressing cells, BAD is constitutively phosphorylated and mainly cytoplasmic,
      whereas in cells expressing BCR/ABL mutants unable to protect from apoptosis, BAD
      is nonphosphorylated. We show here that both the wild-type (WT) and the S112A/
      S136A double mutant (DM) BAD are more potent inducers of apoptosis in parental
      than in BCR/ABL-expressing 32D myeloid precursor cells. Stable lines of parental
      cells expressing DM BAD could not be established and most clones from WT BAD
      retrovirus-infected parental cells lost BAD expression. On IL-3 withdrawal from
      parental 32D cells, BAD was rapidly dephosphorylated by the serine-threonine
      phosphatase 1 alpha, and localized in the mitochondria, whereas it remained
      phosphorylated and did not localize to the mitochondria in the cohort of BCR/ABL
      expressing cells escaping apoptosis induced by WT BAD. Moreover, these cells
      showed high levels of BCL-2 and BCL-X(L) expression. The cohort of BCR/ABL
      expressing cells resistant to apoptosis induced by DM BAD showed only high levels
      of BCL-2 and BCL-X(L). These findings suggest that BCR/ABL-expressing cells are
      more versatile than normal hematopoietic progenitors in counteracting the
      apoptotic potential of BAD, and raise the possibility that tumor cells activate
      multiple antiapoptotic pathways for survival in the face of death-inducing
      stimuli. (Blood. 2000;96:676-684)

PMID- 10887135
TI  - Expression pattern of T-cell-associated chemokine receptors and their chemokines
      correlates with specific subtypes of T-cell non-Hodgkin lymphoma.
AB  - Chemokine receptors mediate the migration of lymphocytes through the binding of
      soluble ligands, and their expression is differentially regulated in lymphocyte
      subsets. The pattern of chemokine receptor expression in T-cell non-Hodgkin
      lymphoma has not been previously studied. Using a panel of mouse monoclonal
      antibodies, we studied the immunohistochemical expression of the Th1-associated
      chemokine receptor CXCR3 in 141 patients with T-cell lymphoma, and we studied the
      receptors CCR4 and CCR5 and some of their ligands in a subset of these tumors.
      Expression of CXCR3 was typical of the smaller T cells in angioimmunoblastic
      lymphoma (15 of 18 patients), angiocentric lymphoma (3 of 3 patients), histiocyte
      rich tumors (4 of 5 patients), and unspecified T-cell lymphomas (17 of 39
      patients). CXCR3 expression was seen in only 1 of 15 patients with anaplastic
      lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma. In contrast, all
      ALK-positive tumors showed diffuse reactivity for the Th2-associated receptor
      CCR4 (5 of 5 patients). CCR4 expression was also a consistent feature of the
      large-cell transformation of mycosis fungoides. CCR5 expression showed no
      consistent association with any T-cell tumor type. The chemokines Mig (CXCR3
      ligand), TARC (CCR4 ligand), and MCP-2 (CCR5 ligand) were detected in
      intratumoral blood vessels and histiocytes. Mig was also coexpressed by a subset
      of CXCR3-positive tumor cells in 6 of 20 lymphomas. MCP-2 was highly expressed in
      stromal cells in 3 patients with nodal involvement by cutaneous T-cell lymphoma.
      As with normal T-cell subsets, we demonstrated that there is frequent
      differential expression of chemokine receptors in T-cell tumors, which may
      explain, in part, the distinctive patterns of spread in different tumor subtypes.
      (Blood. 2000;96:685-690)

PMID- 10887136
TI  - Gi and Gq/11 proteins are involved in dissemination of myeloid leukemia cells to
      the liver and spleen, whereas bone marrow colonization involves Gq/11 but not Gi.
AB  - The migration of leukocytes into tissues is regulated by chemokines and other
      chemotactic factors that act on receptors that signal through Gi proteins. It
      seems likely that the colonization of tissues during dissemination of
      hematopoietic tumor cells is similarly regulated. In fact, dissemination of a T
      cell hybridoma, a model for T lymphoma, was blocked when Gi proteins were
      inactivated by the S1 catalytic subunit of pertussis toxin that had been
      transfected into those cells. Pertussis toxin S1 blocked dissemination of MDAY-D2
      murine myeloid leukemia cells to the liver and spleen, as in T-cell hybridoma
      cells, but it did not prevent bone marrow colonization. In contrast,
      overexpression of a function-defective mutant of the Gq/11 protein blocked
      dissemination to the bone marrow and also prevented Gq/11 dissemination to the
      liver and spleen. This indicates that the influx of these myeloid cells into all
      tissues requires the Gq/11 protein in addition to the Gi protein in the liver and
      spleen. (Blood. 2000;96:691-698)

PMID- 10887137
TI  - ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198
      oligomerization domain.
AB  - An acquired chromosomal translocation, t(8;13)(p11;q11-12), observed in a
      distinctive type of stem cell leukemia/lymphoma syndrome, leads to the fusion of
      the 5' portion of ZNF198 and the 3' portion of FGFR1. ZNF198-FGFR1 fusion
      transcripts encode 4 to 10 zinc fingers, a proline-rich region, and the
      intracellular portion of the FGFR1 (fibroblast growth factor receptor 1) receptor
      tyrosine kinase. We demonstrate that the ZNF198 proline-rich region constitutes a
      novel self-association domain. When fused to the intracellular domain of FGFR1,
      the ZNF198 proline-rich region is sufficient to cause oligomerization, FGFR1
      tyrosine kinase activation, and transformation of Ba/F3 cells to IL-3 independent
      growth. (Blood. 2000;96:699-704)

PMID- 10887138
TI  - Altered lymphoid development in mice deficient for the mAF4 proto-oncogene.
AB  - Some chromosomal translocations in acute leukemias involve the fusion of the
      trithorax-related protein Mll (also called HRX, All1, Htrx,) with a variety of
      heterologous proteins. In acute lymphoblastic leukemia associated with the
      t(4;11)(q21;q23) translocation, the 4q21 gene that fuses with Mll is AF4. To gain
      insight into the potential role of AF4 in leukemogenesis and development, this
      gene was inactivated by homologous recombination in mice. As expected from the
      tissue distribution of the AF4 transcript, development of both B and T cells is
      affected in AF4 mutant mice. A severe reduction of the thymic double positive
      CD4/CD8 (CD4(+)/CD8(+)) population was observed; in addition most double- and
      single-positive cells expressed lower levels of CD4 and CD8 coreceptors. Most
      importantly, the reconstitution of the double-positive compartment by expansion
      of the double-negative cell compartment was severely impaired in these mutant
      mice. In the bone marrow pre-B and mature B-cell numbers are reduced. These
      results demonstrate that the function of the mAF4 gene is critical for normal
      lymphocyte development. This raises the possibility that the disruption of the
      normal AF4 gene or its association with Mll function by translocation may orient
      the oncogenic process toward the lymphoid lineage. This represents the first
      functional study using a knock-out strategy on one of the Mll partner genes in
      translocation-associated leukemias. (Blood. 2000;96:705-710)

PMID- 10887139
TI  - Glucocorticoids promote the proliferation and antagonize the retinoic acid
      mediated growth suppression of Epstein-Barr virus-immortalized B lymphocytes.
AB  - Glucocorticoids are able to release Epstein-Barr virus-immortalized (EBV
      immortalized) lymphoblastoid B cell lines (LCLs) from the persistent growth
      arrest induced in these cells by retinoic acid (RA). Moreover, physiologic
      concentrations of glucocorticoids efficiently antagonized LCL growth inhibition
      induced by 13-cis-RA; 9-cis-RA; all-trans-RA; and Ro 40-6055, an RA alpha
      receptor (RAR alpha) selective agonist. RAR alpha expression levels, however,
      were not affected by glucocorticoids. Glucocorticoids, but not other steroid
      hormones, directly promote LCL proliferation, a phenomenon that was mainly
      mediated by down-regulation of the cyclin-dependent kinase (CDK) inhibitor
      p27(Kip-1). Moreover, glucocorticoids contrasted the up-regulation of p27(Kip-1),
      which was underlying the RA-induced LCL growth arrest, thereby indicating that
      glucocorticoids and RA signalings probably converge on p27(Kip-1). Both
      antagonism of RA-mediated growth inhibition and promotion of LCL proliferation
      were efficiently reversed by the glucocorticoid receptor (GR) antagonist RU486,
      indicating that all of these effects were mediated by GR. Of note, RU486 also
      proved to be effective in vivo and, in mice, was able to significantly inhibit
      the growth of untreated LCLs as well as LCLs growth-arrested by RA in vitro.
      These findings provide a rational background to further evaluate the possible
      role of glucocorticoids in the pathogenesis of EBV-related lymphoproliferations
      of immunosuppressed patients. Moreover, GR antagonists deserve further
      consideration for their possible efficacy in the management of these disorders,
      and the use of schedules, including both RA and a GR antagonist, may allow a more
      thorough evaluation of the therapeutic potential of RA in this setting. (Blood.
      2000;96:711-718)

PMID- 10887140
TI  - Insertion of enhanced green fluorescent protein into the lysozyme gene creates
      mice with green fluorescent granulocytes and macrophages.
AB  - Pluripotent hematopoietic stem cells have been studied extensively, but the
      events that occur during their differentiation remain largely uncharted. To
      develop a system that allows the differentiation of cultured multipotent
      progenitors by time-lapse fluorescence microscopy, myelomonocytic cells were
      labeled with green fluorescent protein (GFP) in vivo. This was achieved by
      knocking the enhanced GFP (EGFP) gene into the murine lysozyme M (lys) locus and
      using a targeting vector, which contains a neomycin resistant (neo) gene flanked
      by LoxP sites and "splinked" ends, to increase the frequency of homologous
      recombination. Analysis of the blood and bone marrow of the lys-EGFP mice
      revealed that most myelomonocytic cells, especially mature neutrophil
      granulocytes, were fluorescence-positive, while cells from other lineages were
      not. Removal of the neo gene through breeding of the mice with the Cre-deleter
      strain led to an increased fluorescence intensity. Mice with an inactivation of
      both copies of the lys gene developed normally and were fertile. (Blood.
      2000;96:719-726)

PMID- 10887141
TI  - Expression of the familial Mediterranean fever gene and activity of the C5a
      inhibitor in human primary fibroblast cultures.
AB  - Familial Mediterranean fever (FMF) is an inherited disease whose manifestations
      are acute but reversible attacks of sterile inflammation affecting synovial and
      serosal spaces. The FMF gene (MEFV) was recently cloned, and it codes for a
      protein (pyrin/marenostrin) homologous to known nuclear factors. We previously
      reported the deficient activity of a C5a/interleukin (IL)-8 inhibitor, a
      physiologic regulator of inflammatory processes, in FMF serosal and synovial
      fluids. We now describe the concomitant expression of MEFV and C5a/IL-8-inhibitor
      activity in primary cultures of human fibroblasts. Fibroblasts grown from
      synovial and peritoneal tissues displayed C5a/IL-8-inhibitor activity that could
      be further induced with phorbol myristate acetate (PMA) and IL-1 beta. Very low
      levels of chemotactic inhibitor were evident in skin fibroblast cultures or in
      peritoneal and skin fibroblasts obtained from FMF patients. MEFV was expressed in
      peritoneal and skin fibroblasts at a lower level than in neutrophils and could be
      further induced by PMA and IL-1 beta. In the FMF cultures, the MEFV transcript
      carried the M694V mutation, consistent with the genetic defect found in patients
      with this disease. MEFV was also expressed in other cell lines that do not
      produce C5a/IL-8 inhibitor. These findings suggest that human primary fibroblast
      cultures express MEFV and produce C5a/IL-8-inhibitor activity. The
      interrelationship between pyrin, the MEFV product, and the C5a/IL-8 inhibitor
      requires further investigation. (Blood. 2000;96:727-731)

PMID- 10887142
TI  - Molecular cloning and characterization of a human metalloprotease disintegrin--a
      novel marker for dendritic cell differentiation.
AB  - The 1alpha,25-dihydroxyvitamin D(3) (1,25- [OH](2)VD(3)) modulates the
      differentiation of monocytic cell lines and monocytes (MOs) in vitro. Up to now
      several target genes of 1,25(OH)(2)VD(3) have been described in monocytic cell
      lines; however, little is known about target genes in primary MOs. With the
      Differential Display technique, we found a transcript up-regulated by
      1,25(OH)(2)VD(3) in short-term cultured human blood MOs, which we called MADDAM
      (metalloprotease and disintegrin dendritic antigen marker; EMBL/GenBank/DDBJ
      accession no. Y13786). Northern blot analysis confirmed this result and revealed
      a signal of MADDAM messenger RNA (mRNA) at about 7.5 kilobases (kb). Long-term
      culture (more than 20 hours) of MOs during macrophage (MAC) differentiation led
      to a rapid and complete down-regulation of MADDAM expression. In contrast, MADDAM
      expression was maintained in MOs differentiated along the dendritic cell (DC)
      pathway and induced in CD34(+)-derived DCs. In addition, in situ hybridization
      revealed signals of MADDAM mRNA in follicles of human lymph nodes and MADDAM mRNA
      was detected in freshly isolated human blood-DCs by reverse transcription
      polymerase chain reaction (RT-PCR). By means of a database search, we found that
      MADDAM is a member of the ADAM (a metalloprotease and disintegrin) family, the
      human homologue to murine meltrin-beta (ADAM 19). From these data, we conclude
      that MADDAM is an important marker for the differentiation and characterization
      of DCs and the distinction between MACs and DCs. (Blood. 2000;96:732-739)

PMID- 10887143
TI  - A novel endoproteolytic processing activity in mitochondria of erythroid cells
      and the role in heme synthesis.
AB  - The erythroid isoform of aminolevulinate synthase (eALAS) protein is a major
      control point in erythroid heme synthesis and hemoglobin formation. Erythroid
      cells were extracted from mouse blood and bone marrow and metabolically labeled
      with (35)S-methionine. This was followed by immunoprecipitation of eALAS protein
      products. The results show that the N-terminus of the expected full-length 59-kd
      form of the eALAS protein is truncated in bone marrow erythroid cells by
      approximately 7 kd. More differentiated erythroid cells in the peripheral blood
      exhibit very little of this protein truncation. Erythroid cells from the bone
      marrow were isolated using monoclonal antibody TER-119 and were shown to contain
      a unique endoprotease activity that could cleave the eALAS protein to the shorter
      form in vitro. With or without the mitochondrial signal sequence, the eALAS
      protein could serve as a substrate for the cleavage. This cleavage renders a
      functional eALAS protein and only removes a domain of unclear function, which has
      previously been reported to vary in size as a result of alternative RNA splicing.
      The protease activity was enriched from the membranes of mitochondria from bone
      marrow cells and was shown to be different from mitochondrial processing
      peptidase, medullasin, and other known proteases. Apart from the mitochondrial
      processing peptidase that cleaves the import signal sequence, this is the first
      description of a mitochondrially located site-specific processing protease
      activity. (Blood. 2000;96:740-746)

PMID- 10887144
TI  - Protein 4.1R binding to eIF3-p44 suggests an interaction between the cytoskeletal
      network and the translation apparatus.
AB  - Erythroid protein 4.1 (4.1R) is an 80-kd cytoskeletal protein that stabilizes the
      membrane-skeletal network structure underlying the lipid bilayer. Using the
      carboxyl terminal domain (22/24 kd) of 4.1R as bait in a yeast 2-hybrid screen,
      we isolated cDNA clones encoding a polypeptide of eIF3-p44, which represents a
      subunit of a eukaryotic translation initiation factor 3 (eIF3) complex. The eIF3
      complex consists of at least 10 subunits that play an essential role in the
      pathway of protein translation initiation. Northern blot analysis revealed that
      eIF3-p44 (approximately 1.35 kb) is constitutively expressed in many tissues. The
      essential sequence for this interaction was mapped to the carboxyl-terminus of
      4.1R (residues 525-622) and a region (residues 54-321) of eIF3-p44. The direct
      association between 4.1R and eIF3-p44 was further confirmed by in vitro binding
      assays and coimmunoprecipitation studies. To characterize the functions of eIF3
      p44, we depleted eIF3-p44 from rabbit reticulocyte lysates either by anti-eIF3
      p44 antibody or by GST/4.1R-80 fusion protein. Our results show that the eIF3-p44
      depleted cell-free translation system was unable to synthesize proteins
      efficiently. The direct association between 4.1R and elF3-p44 suggests that 4.1R
      may act as an anchor protein that links the cytoskeleton network to the
      translation apparatus. (Blood. 2000;96:747-753)

PMID- 10887145
TI  - Prolonged CD4 depletion after sequential autologous peripheral blood progenitor
      cell infusions in children and young adults.
AB  - Administration of mobilized peripheral blood progenitor cells (PBPCs) after high
      dose chemotherapy rapidly restores multilineage hematopoiesis, but the ability of
      such products to restore lymphocyte populations remains unclear. In this report,
      we evaluated immune reconstitution in a series of patients treated with
      sequential cycles of high-dose chemotherapy, followed by autologous PBPC
      infusions (median CD34(+) cell dose 7.2 x 10(6) cells/kg [range 2-29.3]).
      Although patients experienced rapid reconstitution of B cells and CD8(+) T cells,
      we observed CD4 depletion and diminished immune responsiveness in all patients
      for several months after completion of therapy. Mature CD4(+) T cells contained
      within the grafts did not appear to contribute substantially to immune
      reconstitution because CD4 counts did not differ between recipients of
      unmanipulated T-cell replete infusions versus CD34 selected, T-cell-depleted
      infusions. Rather, at 12 months after therapy, total CD4 count was inversely
      proportional to age (rho = -0.78, P =.04), but showed no relationship to CD34
      cell dose (rho = -0.42, P =.26), suggesting that age-related changes within the
      host are largely responsible for the limited immune reconstitution observed.
      These results demonstrate that in the autologous setting, the infusion of large
      numbers of PBPCs is not sufficient to restore T-cell immune competence and
      emphasize that specific approaches to enhance immune reconstitution are necessary
      if immune-based therapy is to be used to eradicate minimal residual disease after
      autologous PBPC transplantation. (Blood. 2000;96:754-762)

PMID- 10887146
TI  - Microchimerism in bone marrow-derived CD34(+) cells of patients after liver
      transplantation.
AB  - Lymphoid and dendritic cells of donor origin can be detected in the recipient
      several years after a solid organ transplantation. This phenomenon is termed
      microchimerism and could play a role in the induction of tolerance. The fate of
      other hematopoietic cells transferred by liver transplantation, in particular of
      stem and progenitor cells, is unknown. For this reason, we studied peripheral
      blood and bone marrow samples of 12 patients who had received a liver transplant
      from an HLA-DR mismatched donor. Eight patients were long-term survivors between
      2.8 and 10.1 years after allografting. CD34(+) cells from bone marrow were highly
      enriched with the use of a 2-step method, and a nested polymerase chain reaction
      was applied to detect donor cells on the basis of allelic differences of the HLA
      DRB1 gene. Rigorous controls with DRB1 specificities equal to the donor and host
      were included. In 5 of 8 long-term liver recipients, donor-specific CD34(+) cells
      could be detected in bone marrow. Microchimerism in the CD34(+) cell fraction did
      not correlate to the chimeric status in peripheral blood. In conclusion, our
      results demonstrate a frequent microchimerism among bone marrow-derived CD34(+)
      cells after liver transplantation. The functional role of this phenomenon still
      needs to be defined. (Blood. 2000;96:763-767)

PMID- 10887147
TI  - Clinical relevance of intracellular vascular endothelial growth factor levels in
      B-cell chronic lymphocytic leukemia.
AB  - Strong evidence exists for an association between high vascular endothelial
      growth factor (VEGF) levels and poor prognoses in patients with solid tumors and
      acute leukemia. Using Western blot analysis and solid-phase radioimmunoassay, we
      measured cellular VEGF levels in B-cell chronic lymphocytic leukemia (CLL)
      samples from 225 patients and correlated these levels with disease
      characteristics and prognoses. The median VEGF level in CLL samples was 7.26
      times the median level detected in normal peripheral blood mononuclear cells.
      Patients with lower levels of VEGF protein showed a trend toward shorter survival
      (P =.07). However, in a subgroup of CLL patients with good prognoses or early
      stage disease (Rai stages 0-II, Binet stages A,B; beta2-M </= 2.8 mg/dL), lower
      levels of VEGF were associated with shorter survival times. For the entire group
      of patients, no correlation was found between VEGF levels and beta2-M levels or
      Rai and Binet stage. Most samples from patients with CLL expressed the 43-kd VEGF
      isoform in addition to the commonly expressed 45-kd isoform. It remains to be
      seen whether the expression of the 43-kd isoform is responsible for this reversed
      correlation with outcome. (Blood. 2000;96:768-770)

PMID- 10887148
TI  - Immunohistochemical staining for megakaryocyte c-mpl may complement morphologic
      distinction between polycythemia vera and secondary erythrocytosis.
AB  - Recent studies have shown decreased megakaryocyte expression of the
      thrombopoietin receptor (c-mpl) in patients with polycythemia vera (PV) but not
      in those with reactive erythrocytosis. We examined the diagnostic utility of this
      observation in 22 patients with PV, 7 patients with secondary erythrocytosis
      (SE), and 10 normal controls. Commercial antibodies against c-mpl were used with
      standard immunoperoxidase methods. Megakaryocyte c-mpl staining intensity was
      uniformly moderate-to-strong in the healthy controls and in all the patients with
      SE. In contrast, staining intensity in 9 patients with PV (41%) was uniformly
      weak. Furthermore, in 12 of the remaining 13 patients with PV, the c-mpl staining
      pattern in each case was heterogeneous and was associated with weak staining
      intensity in more than 20% of the megakaryocyte population. These preliminary
      data suggest that c-mpl immunostains may complement bone marrow histopathology in
      distinguishing PV from nonclonal causes of erythrocytosis. (Blood. 2000;96:771
      772)

PMID- 10887149
TI  - Homozygous truncation of the fibrinogen A alpha chain within the coiled coil
      causes congenital afibrinogenemia.
AB  - The molecular basis of a novel congenital afibrinogenemia has been determined.
      The proposita, the only affected member in a consanguineous Norwegian family,
      suffers from a moderate to severe bleeding disorder due to the total absence of
      any detectable fibrinogen. Dot blots of solubilized platelets revealed a small
      amount of gamma chain but no A alpha or B beta chains, whereas no chains were
      detected in plasma dot blots. DNA sequencing of the A alpha chain gene revealed a
      homozygous C-->T transversion 557 nucleotides from the transcription initiation
      site. This nucleotide change predicts the nonsense mutation A alpha 149 Arg (CGA)
      ->stop (TGA). Early truncation of the A alpha chain appears to result in
      defective assembly or secretion of fibrinogen, probably due to the removal of the
      C-terminal disulfide ring residues that are critically required for the formation
      of a stable 3-chained half molecule. (Blood. 2000;96:773-775)

PMID- 10887150
TI  - CBP/p300 in cell growth, transformation, and development.

PMID- 10887151
TI  - Transgene-mediated cosuppression in the C. elegans germ line.
AB  - Functional silencing of chromosomal loci can be induced by transgenes
      (cosuppression) or by introduction of double-stranded RNA (RNAi). Here, we
      demonstrate the generality of and define rules for a transgene-mediated
      cosuppression phenomenon in the Caenorhabditis elegans germ line. Functional
      repression is not a consequence of persistent physical association between
      transgenes and endogenous genes or of mutations in affected genes. The
      cosuppression mechanism likely involves an RNA mediator that defines its target
      specificity, reminiscent of RNAi. Cosuppression is strongly abrogated in rde-2
      and mut-7 mutants, but is not blocked in an rde-1 mutant, indicating that
      cosuppression and RNAi have overlapping but distinct genetic requirements.

PMID- 10887152
TI  - Cooperative effects of genes controlling the G(2)/M checkpoint.
AB  - It is believed that multiple effectors independently control the checkpoints
      permitting transitions between cell cycle phases. However, this has not been
      rigorously demonstrated in mammalian cells. The p53-induced genes p21 and 14-3
      3sigma are each required for the G(2) arrest and allow a specific test of this
      fundamental tenet. We generated human cells deficient in both p21 and 14-3-3sigma
      and determined whether the double knockout was more sensitive to DNA damage than
      either single knockout. p21(-/-) 14-3-3sigma(-/-) cells were significantly more
      sensitive to DNA damage or to the exogenous expression of p53 than cells lacking
      only p21 or only 14-3-3sigma. Thus, p21 and 14-3-3sigma play distinct but
      complementary roles in the G(2)/M checkpoint, and help explain why genes at the
      nodal points of growth arrest pathways, like p53, are the targets of mutation in
      cancer cells.

PMID- 10887153
TI  - Error-prone bypass of certain DNA lesions by the human DNA polymerase kappa.
AB  - The Escherichia coli protein DinB is a newly identified error-prone DNA
      polymerase. Recently, a human homolog of DinB was identified and named DINB1. We
      report that the DINB1 gene encodes a DNA polymerase (designated polkappa), which
      incorporates mismatched bases on a nondamaged template with a high frequency.
      Moreover, polkappa bypasses an abasic site and N-2-acetylaminofluorene (AAF)
      adduct in an error-prone manner but does not bypass a cis-syn or (6-4) thymine
      thymine dimer or a cisplatin-adduct. Therefore, our results implicate an
      important role for polkappa in the mutagenic bypass of certain types of DNA
      lesions.

PMID- 10887154
TI  - A conserved family of calcineurin regulators.
AB  - The protein phosphatase calcineurin mediates many cellular responses to calcium
      signals. Using a genetic screen in yeast, we identified a new family of proteins
      conserved in fungi and animals that inhibit calcineurin function when
      overexpressed. Overexpression of the yeast protein Rcn1p or the human homologs
      DSCR1 or ZAKI-4 inhibited two independent functions of calcineurin in yeast: The
      activation of the transcription factor Tcn1p and the inhibition of the
      H(+)/Ca(2+) exchanger Vcx1p. Purified recombinant Rcn1p and DSCR1 bound
      calcineurin in vitro and inhibited its protein phosphatase activity. Signaling
      via calmodulin, calcineurin, and Tcn1p induced Rcn1p expression, suggesting that
      Rcn1p operates as an endogenous feedback inhibitor of calcineurin. Surprisingly,
      rcn1 null mutants exhibited phenotypes similar to those of Rcn1p-overexpressing
      cells. This effect may be due to lower expression of calcineurin in rcn1 mutants
      during signaling conditions. Thus, Rcn1p levels may fine-tune calcineurin
      signaling in yeast. The structural and functional conservation between Rcn1p and
      DSCR1 suggests that the mammalian Rcn1p-related proteins, termed calcipressins,
      will modulate calcineurin signaling in humans and potentially contribute to
      disorders such as Down Syndrome.

PMID- 10887155
TI  - A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF
      beta signal transduction.
AB  - Members of the transforming growth factor-beta superfamily play critical roles in
      controlling cell growth and differentiation. Effects of TGF-beta family ligands
      are mediated by Smad proteins. To understand the mechanism of Smad function, we
      sought to identify novel interactors of Smads by use of a yeast two-hybrid
      system. A 396-amino acid nuclear protein termed SNIP1 was cloned and shown to
      harbor a nuclear localization signal (NLS) and a Forkhead-associated (FHA)
      domain. The carboxyl terminus of SNIP1 interacts with Smad1 and Smad2 in yeast
      two-hybrid as well as in mammalian overexpression systems. However, the amino
      terminus of SNIP1 harbors binding sites for both Smad4 and the coactivator
      CBP/p300. Interaction between endogenous levels of SNIP1 and Smad4 or CBP/p300 is
      detected in NMuMg cells as well as in vitro. Overexpression of full-length SNIP1
      or its amino terminus is sufficient to inhibit multiple gene responses to TGF
      beta and CBP/p300, as well as the formation of a Smad4/p300 complex. Studies in
      Xenopus laevis further suggest that SNIP1 plays a role in regulating dorsomedial
      mesoderm formation by the TGF-beta family member nodal. Thus, SNIP1 is a nuclear
      inhibitor of CBP/p300 and its level of expression in specific cell types has
      important physiological consequences by setting a threshold for TGF-beta-induced
      transcriptional activation involving CBP/p300.

PMID- 10887156
TI  - Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human
      neurofibromatosis type 2.
AB  - Hemizygosity for the NF2 gene in humans causes a syndromic susceptibility to
      schwannoma development. However, Nf2 hemizygous mice do not develop schwannomas
      but mainly osteosarcomas. In the tumors of both species, the second Nf2 allele is
      inactivated. We report that conditional homozygous Nf2 knockout mice with Cre
      mediated excision of Nf2 exon 2 in Schwann cells showed characteristics of
      neurofibromatosis type 2. These included schwannomas, Schwann cell hyperplasia,
      cataract, and osseous metaplasia. Thus, the tumor suppressor function of Nf2,
      here revealed in murine Schwann cells, was concealed in hemizygous Nf2 mice
      because of insufficient rate of second allele inactivation in this cell
      compartment. The finding of this conserved function documents the relevance of
      the present approach to model the human disease.

PMID- 10887157
TI  - Cdc6p modulates the structure and DNA binding activity of the origin recognition
      complex in vitro.
AB  - An interaction between the origin recognition complex (ORC) and Cdc6p is the
      first and a key step in the initiation of chromosomal DNA replication. We
      describe the assembly of an origin-dependent complex containing ORC and Cdc6p
      from Saccharomyces cerevisiae. Cdc6p increases the DNA binding specificity of ORC
      by inhibiting non-specific DNA binding of ORC. Cdc6p induces a concomitant change
      in the conformation of ORC and mutations in the Cdc6p Walker A and Walker B
      motifs, or ATP-gamma-S inhibited these activities of Cdc6p. These data suggest
      that Cdc6p modifies ORC function at DNA replication origins. On the basis of
      these results in yeast, we propose that Cdc6p may be an essential determinant of
      origin specificity in metazoan species.

PMID- 10887158
TI  - poliota, a remarkably error-prone human DNA polymerase.
AB  - The Saccharomyces cerevisiae RAD30 gene encodes DNA polymerase eta. Humans
      possess two Rad30 homologs. One (RAD30A/POLH) has previously been characterized
      and shown to be defective in humans with the Xeroderma pigmentosum variant
      phenotype. Here, we report experiments demonstrating that the second human
      homolog (RAD30B), also encodes a novel DNA polymerase that we designate poliota.
      poliota, is a distributive enzyme that is highly error-prone when replicating
      undamaged DNA. At template G or C, the average error frequency was approximately
      1 x 10(-2). Our studies revealed, however, a striking asymmetry in
      misincorporation frequency at template A and T. For example, template A was
      replicated with the greatest accuracy, with misincorporation of G, A, or C
      occurring with a frequency of approximately 1 x 10(-4) to 2 x 10(-4). In dramatic
      contrast, most errors occurred at template T, where the misincorporation of G
      was, in fact, favored approximately 3:1 over the correct nucleotide, A, and
      misincorporation of T occurred at a frequency of approximately 6.7 x 10(-1).
      These findings demonstrate that poliota is one of the most error-prone eukaryotic
      polymerases reported to date and exhibits an unusual misincorporation spectrum in
      vitro.

PMID- 10887159
TI  - A family of rhomboid-like genes: Drosophila rhomboid-1 and roughoid/rhomboid-3
      cooperate to activate EGF receptor signaling.
AB  - As in mammals, the Drosophila EGF receptor controls many aspects of growth and
      development. The rate limiting component of Drosophila Egfr signaling is
      Rhomboid, a seven transmembrane domain protein, whose expression prefigures Egfr
      signaling. Little is known about the molecular mechanism of Rhomboid function but
      genetic evidence suggests that it controls the activation of the ligand Spitz, a
      TGFalpha-like factor. Spitz/Egfr signaling regulates cell determination in the
      eye but here there is no apparent function for Rhomboid, an observation that
      casts doubt on this prevailing model of Rhomboid function. We describe our
      identification of six new rhomboid-like genes in Drosophila, and a large family
      of related genes present in organisms as diverse as bacteria and mammals; a human
      rhomboid homolog has also recently been described. Drosophila rhomboid-3
      corresponds to the roughoid mutation; it cooperates with rhomboid-1 to control
      Egfr signaling in the eye, thereby solving the puzzle of the apparent lack of
      Rhomboid-1 function there. Rhomboid-1 and Roughoid/Rhomboid-3 act in the signal
      emitting not signal-receiving cell, supporting the idea that Spitz activation is
      regulated by Rhomboid-like molecules.

PMID- 10887160
TI  - Coregulation of anterior and posterior mesendodermal development by a hairy
      related transcriptional repressor.
AB  - During embryonic development in vertebrates, the endoderm becomes patterned along
      the anteroposterior axis to produce distinct derivatives. How this regulation is
      controlled is not well understood. We report that the zebrafish hairy/enhancer of
      split [E(spl)]-related gene her5 plays a critical role in this process. At
      gastrulation, following endoderm induction and further cell interaction processes
      including a local release of Notch/Delta signaling, her5 expression is
      progressively excluded from the presumptive anterior- and posteriormost
      mesendodermal territories to become restricted to an adjacent subpopulation of
      dorsal endodermal precursors. Ectopic misexpressions of wild-type and mutant
      forms of her5 reveal that her5 functions primarily within the endodermal/endmost
      mesendodermal germ layer to inhibit cell participation to the endmost-fated
      mesendoderm. In this process, her5 acts as an active transcriptional repressor.
      These features are strikingly reminiscent of the function of Drosophila
      Hairy/E(spl) factors in cell fate decisions. Our results provide the first model
      for vertebrate endoderm patterning where an early regulatory step at
      gastrulation, mediated by her5 controls cell contribution jointly to the anterior
      and posteriormost mesendodermal regions.

PMID- 10887161
TI  - Control of her1 expression during zebrafish somitogenesis by a delta-dependent
      oscillator and an independent wave-front activity.
AB  - Somitogenesis has been linked both to a molecular clock that controls the
      oscillation of gene expression in the presomitic mesoderm (PSM) and to Notch
      pathway signaling. The oscillator, or clock, is thought to create a prepattern of
      stripes of gene expression that regulates the activity of the Notch pathway that
      subsequently directs somite border formation. Here, we report that the zebrafish
      gene after eight (aei) that is required for both somitogenesis and neurogenesis
      encodes the Notch ligand DeltaD. Additional analysis revealed that stripes of
      her1 expression oscillate within the PSM and that aei/DeltaD signaling is
      required for this oscillation. aei/DeltaD expression does not oscillate,
      indicating that the activity of the Notch pathway upstream of her1 may function
      within the oscillator itself. Moreover, we found that her1 stripes are expressed
      in the anlage of consecutive somites, indicating that its expression pattern is
      not pair-rule. Analysis of her1 expression in aei/DeltaD, fused somites (fss),
      and aei;fss embryos uncovered a wave-front activity that is capable of
      continually inducing her1 expression de novo in the anterior PSM in the absence
      of the oscillation of her1. The wave-front activity, in reference to the clock
      and wave-front model, is defined as such because it interacts with the oscillator
      derived pattern in the anterior PSM and is required for somite morphogenesis.
      This wave-front activity is blocked in embryos mutant for fss but not aei/DeltaD.
      Thus, our analysis indicates that the smooth sequence of formation, refinement,
      and fading of her1 stripes in the PSM is governed by two separate activities.

PMID- 10887162
TI  - Toward vocabulary domain specifications for health level 7-coded data elements.
AB  - The "vocabulary problem" has long plagued the developers, implementers, and users
      of computer-based systems. The authors review selected activities of the Health
      Level 7 (HL7) Vocabulary Technical Committee that are related to vocabulary
      domain specification for HL7 coded data elements. These activities include: 1)
      the development of two sets of principles to provide guidance to terminology
      stakeholders, including organizations seeking to deploy HL7-compliant systems,
      terminology developers, and terminology integrators; 2) the completion of a
      survey of terminology developers; 3) the development of a process for HL7
      registration of terminologies; and 4) the maintenance of vocabulary domain
      specification tables. As background, vocabulary domain specification is defined
      and the relationship between the HL7 Reference Information Model and vocabulary
      domain specification is described. The activities of the Vocabulary Technical
      Committee complement the efforts of terminology developers and other
      stakeholders. These activities are aimed at realizing semantic interoperability
      in the context of the HL7 Message Development Framework, so that information
      exchange and use among disparate systems can occur for the delivery and
      management of direct clinical care as well as for purposes such as clinical
      research, outcome research, and population health management.

PMID- 10887163
TI  - WebEAV: automatic metadata-driven generation of web interfaces to entity
      attribute-value databases.
AB  - The task of creating and maintaining a front end to a large institutional entity
      attribute-value (EAV) database can be cumbersome when using traditional client
      server technology. Switching to Web technology as a delivery vehicle solves some
      of these problems but introduces others. In particular, Web development
      environments tend to be primitive, and many features that client-server
      developers take for granted are missing. WebEAV is a generic framework for Web
      development that is intended to streamline the process of Web application
      development for databases having a significant EAV component. It also addresses
      some challenging user interface issues that arise when any complex system is
      created. The authors describe the architecture of WebEAV and provide an overview
      of its features with suitable examples.

PMID- 10887164
TI  - Integrating data from legacy systems using object linking and embedding
      technology: development of a reporting system for heavy metal poisoning results.
AB  - Integrating data that reside in different systems remains an often laborious
      process, requiring either manual steps or complicated programming. This paper
      describes a method for state-mandated reporting of childhood blood lead testing
      results that makes use of object linking and embedding technology and readily
      available software products to pull together information from different legacy
      systems. A terminal session emulator employs object linking and embedding
      automation to extract host data, and Visual Basic routines specify the user
      interface and database manipulation. This system has significantly increased the
      efficiency and accuracy with which blood lead testing reports are provided to the
      local state health department. The system provides a model for a relatively easy
      solution for laboratories and other groups that need a way to integrate standard
      data sets that are distributed across legacy systems.

PMID- 10887165
TI  - Building a virtual network in a community health research training program.
AB  - OBJECTIVE: To describe the experiences, lessons, and implications of building a
      virtual network as part of a two-year community health research training program
      in a Canadian province. DESIGN: An action research field study in which 25 health
      professionals from 17 health regions participated in a seven-week training course
      on health policy, management, economics, research methods, data analysis, and
      computer technology. The participants then returned to their regions to apply the
      knowledge in different community health research projects. Ongoing faculty
      consultations and support were provided as needed. Each participant was given a
      notebook computer with the necessary software, Internet access, and technical
      support for two years, to access information resources, engage in group problem
      solving, share ideas and knowledge, and collaborate on projects. MEASUREMENTS:
      Data collected over two years consisted of program documents, records of
      interviews with participants and staff, meeting notes, computer usage statistics,
      automated online surveys, computer conference postings, program Web site, and
      course feedback. The analysis consisted of detailed review and comparison of the
      data from different sources. NUD*IST was then used to validate earlier study
      findings. RESULTS: The ten key lessons are that role clarity, technology vision,
      implementation staging, protected time, just-in-time training, ongoing
      facilitation, work integration, participatory design, relationship building, and
      the demonstration of results are essential ingredients for building a successful
      network. CONCLUSION: This study provides a descriptive model of the processes
      involved in developing, in the community health setting, virtual networks that
      can be used as the basis for future research and as a practical guide for
      managers.

PMID- 10887166
TI  - Fast exact string pattern-matching algorithms adapted to the characteristics of
      the medical language.
AB  - OBJECTIVE: The authors consider the problem of exact string pattern matching
      using algorithms that do not require any preprocessing. To choose the most
      appropriate algorithm, distinctive features of the medical language must be taken
      into account. The characteristics of medical language are emphasized in this
      regard, the best algorithm of those reviewed is proposed, and detailed
      evaluations of time complexity for processing medical texts are provided. DESIGN:
      The authors first illustrate and discuss the techniques of various string pattern
      matching algorithms. Next, the source code and the behavior of representative
      exact string pattern-matching algorithms are presented in a comprehensive manner
      to promote their implementation. Detailed explanations of the use of various
      techniques to improve performance are given. MEASUREMENTS: Real-time measures of
      time complexity with English medical texts are presented. They lead to results
      distinct from those found in the computer science literature, which are typically
      computed with normally distributed texts. RESULTS: The Boyer-Moore-Horspool
      algorithm achieves the best overall results when used with medical texts. This
      algorithm usually performs at least twice as fast as the other algorithms tested.
      CONCLUSION: The time performance of exact string pattern matching can be greatly
      improved if an efficient algorithm is used. Considering the growing amount of
      text handled in the electronic patient record, it is worth implementing this
      efficient algorithm.

PMID- 10887167
TI  - Evaluation of the quality of information retrieval of clinical findings from a
      computerized patient database using a semantic terminological model.
AB  - OBJECTIVES: To measure the strength of agreement between the concepts and records
      retrieved from a computerized patient database, in response to physician-derived
      questions, using a semantic terminological model for clinical findings with those
      concepts and records excerpted clinically by manual identification. The
      performance of the semantic terminological model is also compared with the more
      established retrieval methods of free-text search, ICD-10, and hierarchic
      retrieval. DESIGN: A clinical database (Diabeta) of 106,000 patient problem
      record entries containing 2,625 unique concepts in an clinical academic
      department was used to compare semantic, free-text, ICD-10, and hierarchic data
      retrieval against a gold standard in response to a battery of 47 clinical
      questions. MEASUREMENTS: The performance of concept and record retrieval
      expressed as mean detection rate, positive predictive value, Yates corrected and
      Mantel-Haenszel chi-squared values, and Cohen kappa value, with significance
      estimated using the Mann-Whitney test. RESULTS: The semantic terminological model
      used to retrieve clinically useful concepts from a patient database performed
      well and better than other methods, with a mean detection rate of 0.86, a
      positive predictive value of 0.96, a Yates corrected chi-squared value of 1,537,
      a Mantel-Haenszel chi-squared value of 19,302, and a Cohen kappa of 0.88. Results
      for record retrieval were even better, with a mean record detection rate of 0.94,
      a positive predictive value of 0.99, a Yates corrected chi-squared value of 94,
      774, a Mantel-Haenszel chi-squared value of 1,550,356, and a Cohen kappa value of
      0.94. The mean detection rate, Yates corrected chi-squared value, and Cohen kappa
      value for semantic retrieval were significantly better than for the other
      methods. CONCLUSION: The use of a semantic terminological model in this test
      scenario provides an effective framework for representing clinical finding
      concepts and their relationships. Although currently incomplete, the model
      supports improved information retrieval from a patient database in response to
      clinically relevant questions, when compared with alternative methods of
      analysis.

PMID- 10887168
TI  - PathMaster: content-based cell image retrieval using automated feature
      extraction.
AB  - OBJECTIVE: Currently, when cytopathology images are archived, they are typically
      stored with a limited text-based description of their content. Such a description
      inherently fails to quantify the properties of an image and refers to an
      extremely small fraction of its information content. This paper describes a
      method for automatically indexing images of individual cells and their associated
      diagnoses by computationally derived cell descriptors. This methodology may serve
      to better index data contained in digital image databases, thereby enabling
      cytologists and pathologists to cross-reference cells of unknown etiology or
      nature. DESIGN: The indexing method, implemented in a program called PathMaster,
      uses a series of computer-based feature extraction routines. Descriptors of
      individual cell characteristics generated by these routines are employed as
      indexes of cell morphology, texture, color, and spatial orientation.
      MEASUREMENTS: The indexing fidelity of the program was tested after populating
      its database with images of 152 lymphocytes/lymphoma cells captured from lymph
      node touch preparations stained with hematoxylin and eosin. Images of "unknown"
      lymphoid cells, previously unprocessed, were then submitted for feature
      extraction and diagnostic cross-referencing analysis. RESULTS: PathMaster listed
      the correct diagnosis as its first differential in 94 percent of recognition
      trials. In the remaining 6 percent of trials, PathMaster listed the correct
      diagnosis within the first three "differentials." CONCLUSION: PathMaster is a
      pilot cell image indexing program/search engine that creates an indexed reference
      of images. Use of such a reference may provide assistance in the
      diagnostic/prognostic process by furnishing a prioritized list of possible
      identifications for a cell of uncertain etiology.

PMID- 10887169
TI  - Methods for the design and administration of web-based surveys.
AB  - This paper describes the design, development, and administration of a Web-based
      survey to determine the use of the Internet in clinical practice by 450 dental
      professionals. The survey blended principles of a controlled mail survey with
      data collection through a Web-based database application. The survey was
      implemented as a series of simple HTML pages and tested with a wide variety of
      operating environments. The response rate was 74.2 percent. Eighty-four percent
      of the participants completed the Web-based survey, and 16 percent used e-mail or
      fax. Problems identified during survey administration included
      incompatibilities/technical problems, usability problems, and a programming
      error. The cost of the Web-based survey was 38 percent less than that of an
      equivalent mail survey. A general formula for calculating breakeven points
      between electronic and hardcopy surveys is presented. Web-based surveys can
      significantly reduce turnaround time and cost compared with mail surveys and may
      enhance survey item completion rates.

PMID- 10887170
TI  - When to use web-based surveys.

PMID- 10887171
TI  - Functional dichotomy of protein kinase C (PKC) in tumor necrosis factor-alpha
      (TNF-alpha ) signal transduction in L929 cells. Translocation and inactivation of
      PKC by TNF-alpha.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is capable of inducing a variety of
      biologic responses through multiple signaling pathways. Because of the potential
      role of protein kinase C (PKC) in apoptosis, we examined the effects and
      mechanisms of TNF-alpha on PKC regulation, specifically on PKC alpha. In L929
      murine fibroblasts, TNF-alpha (0.5- 5 nm) caused potent inhibition of PKC alpha
      activity and induced translocation of PKC alpha from the cytosol to the membrane.
      Treatment of cells with TNF-alpha also induced dephosphorylation of PKC alpha as
      detected by a mobility shift on SDS-polyacrylamide gel and inhibition of PKC
      phosphorylation as probed by anti-phospho-PKC antibodies. Since PKC is activated
      directly by diacylglycerol and inactivated indirectly by ceramide, we next
      examined the roles of these lipid mediators in the regulation of PKC alpha.
      Addition of TNF-alpha led to accumulation of both ceramide and diacylglycerol.
      Fumonisin B(1), an inhibitor of ceramide synthase, and glutathione, an inhibitor
      of neutral sphingomyelinase, both reversed the effect of TNF-alpha on PKC alpha
      activity, suggesting that ceramide production is necessary for the action of TNF
      alpha. The diacylglycerol mimic phorbol 12-myristate 13-acetate was sufficient to
      cause translocation of PKC alpha, but not the mobility shift. Okadaic acid at 2
      nm, a potent protein phosphatase inhibitor, blocked the effects of TNF-alpha on
      PKC alpha activity, but not on PKC alpha translocation, thus demonstrating that
      dephosphorylation and translocation are independent processes. These results
      demonstrate that PKC alpha acts as a downstream target for TNF-alpha and that
      different lipid-mediated pathways in TNF-alpha signaling lead to opposing signals
      in the regulation of PKC alpha activity.

PMID- 10887172
TI  - Rb-independent induction of apoptosis by bovine papillomavirus type 1 E7 in
      response to tumor necrosis factor alpha.
AB  - Bovine papillomavirus type 1 (BPV-1) is a small DNA virus that causes
      fibropapillomas of the host. BPV-1 has served as the prototype for studies of the
      molecular biology of the papillomaviruses. BPV-1 efficiently induces anchorage
      independent growth and focus formation in murine C127 cells. The transforming
      properties of BPV-1 primarily reside in two genes, E5 and E6. Each of these genes
      is sufficient to transform cells. Although no independent transformation activity
      has been detected for E7, it was shown to be required for full transformation of
      C127 by BPV-1. We investigated the biological activities of BPV-1 E7 in several
      assays. Our results indicate that expression of BPV-1 E7 sensitizes cells to
      tumor necrosis factor alpha (TNF)-induced apoptosis. The TNF-induced apoptosis in
      E7-expressing cells was accompanied by increased release of arachidonic acid,
      indicating that phospholipase A(2) was activated. Unlike the E7 proteins from the
      cancer-related human papillomaviruses, the BPV-1 E7 protein does not associate
      efficiently with the retinoblastoma protein (pRB) in vitro, nor does it
      significantly affect the pRB levels in cultured cells. Furthermore, BPV-1 E7
      sensitizes Rb-null cells to TNF-induced apoptosis. These studies indicate that
      BPV-1 E7 can sensitize cells to apoptosis through mechanisms that are independent
      of pRB.

PMID- 10887173
TI  - Calyculin A-induced vimentin phosphorylation sequesters 14-3-3 and displaces
      other 14-3-3 partners in vivo.
AB  - 14-3-3 proteins bind their targets through a specific serine/threonine
      phosphorylated motif present on the target protein. This binding is a crucial
      step in the phosphorylation-dependent regulation of various key proteins involved
      in signal transduction and cell cycle control. We report that treatment of COS-7
      cells with the phosphatase inhibitor calyculin A induces association of 14-3-3
      with a 55-kDa protein, identified as the intermediate filament protein vimentin.
      Association of vimentin with 14-3-3 depends on vimentin phosphorylation and
      requires the phosphopeptide-binding domain of 14-3-3. The region necessary for
      binding to 14-3-3 is confined to the vimentin amino-terminal head domain (amino
      acids 1-96). Monomeric forms of 14-3-3 do not bind vimentin in vivo or in vitro,
      indicating that a stable complex requires the binding of a 14-3-3 dimer to two
      sites on a single vimentin polypeptide. The calyculin A-induced association of
      vimentin with 14-3-3 in vivo results in the displacement of most other 14-3-3
      partners, including the protooncogene Raf, which nevertheless remain capable of
      binding 14-3-3 in vitro. Concomitant with 14-3-3 displacement, calyculin A
      treatment blocks Raf activation by EGF; however, this inhibition is completely
      overcome by 14-3-3 overexpression in vivo or by the addition of prokaryotic
      recombinant 14-3-3 in vitro. Thus, phosphovimentin, by sequestering 14-3-3 and
      limiting its availability to other target proteins can affect intracellular
      signaling processes that require 14-3-3.

PMID- 10887174
TI  - Inflammatory versus proliferative processes in epidermis. Tumor necrosis factor
      alpha induces K6b keratin synthesis through a transcriptional complex containing
      NFkappa B and C/EBPbeta.
AB  - Epidermal keratinocytes respond to injury by becoming activated, i.e.
      hyperproliferative, migratory, and proinflammatory. These processes are regulated
      by growth factors and cytokines. One of the markers of activated keratinocytes is
      keratin K6. We used a novel organ culture system to show that tumor necrosis
      factor alpha (TNFalpha) induces the expression of K6 protein and mRNA in human
      skin. Multiple isoforms of K6 are encoded by distinct genes and have distinct
      patterns of expression. By having shown previously that proliferative signals,
      such as epidermal growth factor (EGF), induce expression of the cytoskeletal
      protein keratin K6b, we here demonstrate that the same isoform, K6b, is also
      induced by TNFalpha, a proinflammatory cytokine. Specifically, TNFalpha induces
      the transcription of the K6b gene promoter. By using co-transfection, specific
      inhibitors, and antisense oligonucleotides, we have identified NFkappaB and
      C/EBPbeta as the transcription factors that convey the TNFalpha signal. Both
      transcription factors are necessary for the induction of K6b by TNFalpha and act
      as a complex, although only C/EBPbeta binds the K6b promoter DNA. By using
      transfection, site-directed mutagenesis, and footprinting, we have mapped the
      site that responds to TNFalpha, NFkappaB, and C/EBPbeta. This site is separate
      from the one responsive to EGF and AP1. Our results show that the proinflammatory
      (TNFalpha) and the proliferative (EGF) signals in epidermis separately and
      independently regulate the expression of the same K6b keratin isoform. Thus, the
      cytoskeletal responses in epidermal cells can be precisely tuned by separate
      proliferative and inflammatory signals to fit the nature of the injuries that
      caused them.

PMID- 10887175
TI  - Morphine induces gene expression of CCR5 in human CEMx174 lymphocytes.
AB  - All HIV-1 strains studied to date use CCR5, CXCR4, or both receptors to enter
      cells. Simian immunodeficiency virus (SIV) infection of non-human primates has
      served as a useful model for understanding AIDS pathogenesis in humans. Research
      on several genetically divergent SIV isolates has revealed that SIV uses CCR5,
      and not CXCR4, for entry. CEM x174, a human lymphoid cell line, has been
      routinely used to cultivate and maintain various SIV strains. However, questions
      have arisen about how CEM x174, which reportedly was unable to express detectable
      amounts of CCR5 transcripts, efficiently supports the growth of SIV. In searching
      for an answer, we resorted to a sensitive competitive reverse transcriptase
      polymerase chain reaction procedure in an attempt to detect as well as quantify
      the amount of CCR5 expression. Here we present our findings, which indicate that
      CEM x174 indeed expresses CCR5 and that the amount of CCR5 is increased in cells
      pretreated with morphine. These results correlate well with our previous
      observations that morphine treatment causes CEM x174 cells to be more susceptible
      to SIV infection. Similar morphine effect was not observed on CEM x174 cells
      infected with simian retroviruses, which do not depend on CCR5 for entry. These
      findings suggest a plausible mechanism whereby opiate drug users render
      themselves more susceptible to HIV infection, thereby explaining the vast
      prevalence of HIV infection among endemic drug use populations.

PMID- 10887177
TI  - Functional independence of the two cysteine-rich activation domains in the yeast
      Mac1 transcription factor.
AB  - Mac1 is a transcriptional activator whose activity is inhibited by copper ions.
      Mutagenesis studies were carried out to map residues important in the copper
      inhibition of Mac1 activity. Seven new missense mutations were identified that
      resulted in copper-independent Mac1 transcriptional activation. All seven
      mutations were clustered in one of two C-terminal cysteine-rich motifs,
      designated the C1 motif. All but one of the constitutive Mac1 mutations occurred
      in one of the conserved six residues in the
      (264)CXC[(X)(4)]CXC[(X)(2)]C[(X)(2)][H(279)]C1 motif. The lone exception was a
      L260S substitution. Two additional MAC1 mutations exhibiting constitutive
      activity were in-frame deletions encompassing portions C1. Engineered mutations
      in the second cysteine-rich motif did not yield a constitutively active Mac1.
      These results are consistent with the C1 motif being the copper-regulatory
      switch. Both cysteine-rich motifs exhibited transactivation activity, although
      the C1 activator was weak relative to the C2 activator. Limited copper
      metalloregulation of Mac1 was observed with only the C1 activator fused to the N
      terminal DNA binding domain. Thus, the two Cys-rich motifs appear to function
      independently. The C1 motif appears to be a functional copper-regulatory domain.

PMID- 10887176
TI  - A novel pharmacological approach to treating cardiac ischemia. Binary conjugates
      of A1 and A3 adenosine receptor agonists.
AB  - Adenosine released during cardiac ischemia exerts a potent, protective effect in
      the heart via activation of A(1) or A(3) receptors. However, the interaction
      between the two cardioprotective adenosine receptors and the question of which
      receptor is the more important anti-ischemic receptor remain largely unexplored.
      The objective of this study was to test the hypothesis that activation of both
      receptors exerted a cardioprotective effect that was significantly greater than
      activation of either receptor individually. This was accomplished by using a
      novel design in which new binary conjugates of adenosine A(1) and A(3) receptor
      agonists were synthesized and tested in a novel cardiac myocyte model of
      adenosine-elicited cardioprotection. Binary drugs having mixed selectivity for
      both A(1) and A(3) receptors were created through the covalent linking of
      functionalized congeners of adenosine agonists, each being selective for either
      the A(1) or A(3) receptor subtype. MRS 1740 and MRS 1741, thiourea-linked,
      regioisomers of a binary conjugate, were highly potent and selective in
      radioligand binding assays for A(1) and A(3) receptors (K(i) values of 0.7-3.5
      nm) versus A(2A) receptors. The myocyte models utilized cultured chick embryo
      cells, either ventricular cells expressing native adenosine A(1) and A(3)
      receptors, or engineered atrial cells, in which either human A(3) receptors alone
      or both human A(1) and A(3) receptors were expressed. The binary agonist MRS 1741
      coactivated A(1) and A(3) receptors simultaneously, with full cardioprotection
      (EC(50) approximately 0.1 nm) dependent on expression of both receptors. Thus, co
      activation of both adenosine A(1) and A(3) receptors by the binary A(1)/A(3)
      agonists represents a novel general cardioprotective approach for the treatment
      of myocardial ischemia.

PMID- 10887178
TI  - Sprouty proteins are targeted to membrane ruffles upon growth factor receptor
      tyrosine kinase activation. Identification of a novel translocation domain.
AB  - Sprouty (Spry) was first identified in a genetic screen in Drosophila to be an
      antagonist of fibroblast growth factor and epidermal growth factor (EGF)
      signaling, seemingly by inhibiting the Ras/MAP kinase pathway. Data base searches
      lead to the identification and cloning of, to date, four mammalian sprouty genes.
      The primary sequences of the mammalian sprouty gene products share a well
      conserved cysteine-rich C-terminal domain with the Drosophila protein. The N
      terminal regions, however, do not exhibit significant homology. This study aimed
      at determining the disposition of Spry proteins in intact cells before and after
      stimulation of the EGF receptor tyrosine kinase. Full-length or deletion mutants
      of Spry, tagged at the N termini with the FLAG-epitope, were expressed in COS-1
      cells by transient transfection and analyzed by immunofluorescence microscopy
      before and after EGF stimulation of the cells. In unstimulated cells, the Spry
      proteins were distributed throughout the cytosol except for human Sprouty2
      (hSpry2), which, although generally located in the cytosol, co-localized with
      microtubules. In all cases, the Spry proteins underwent rapid translocation to
      membrane ruffles following EGF stimulation. The optimal translocation domain was
      identified by deletion and immunofluorescence analysis to be a highly conserved
      105-amino acid domain in the C-terminal half of the hSpry2 protein. The
      translocation of this conserved domain, based on hSpry2 data, was independent of
      the activation of phosphatidylinositol-3 kinase.

PMID- 10887179
TI  - Interaction of mammalian mitochondrial ribosomes with the inner membrane.
AB  - All of the products of mitochondrial protein biosynthesis in animals are
      hydrophobic proteins that are localized in the inner membrane. Hence, it is
      possible that the synthesis of these proteins could occur on ribosomes associated
      with the inner membrane. To examine this possibility, inner membrane and matrix
      fractions of bovine mitochondria were examined for the presence of ribosomes
      using probes for the rRNAs. Between 40 and 50% of the ribosomes were found to
      fractionate with the inner membrane. About half of the ribosomes associated with
      the inner membrane could be released by high salt treatment, indicating that they
      interact with the membrane largely through electrostatic forces. No release of
      the ribosome was observed upon treatment with puromycin, suggesting that the
      association observed is not due to insertion of a nascent polypeptide chain into
      the membrane. A fraction of the ribosomes remained with residual portions of the
      membranes that cannot be solubilized in the presence of Triton X-100. These
      ribosomes may be associated with large oligomeric complexes in the membrane.

PMID- 10887180
TI  - The coiled-coil domain of occludin can act to organize structural and functional
      elements of the epithelial tight junction.
AB  - Occludin is an integral membrane protein that has been suggested to play a role
      in the organization and dynamic function of the epithelial tight junction (TJ). A
      number of other proteins have also been described to localize to the TJ. We have
      used a novel bait peptide method to investigate potential protein-protein
      interactions of the putative coiled-coil domain of occludin with some of these
      other TJ proteins. A 27-amino acid peptide of the human occludin sequence was
      synthesized, biotinylated at the N terminus, and modified to contain a
      photoactive moiety at either its hydrophobic or hydrophilic surface. These bait
      peptides were alpha-helical in solution, characteristic of coiled-coil
      structures. Photoactivation studies in the presence and absence of control
      peptides were used to assess the potential interactions in polarized sheets of a
      human intestinal cell line T84. Although a large number of proteins associated
      with the TJ or that are known to be involved in regulatory events of epithelial
      cells failed to be specifically labeled, occludin itself, ZO-1, protein kinase C
      zeta, c-Yes, the regulatory subunit of phosphatidylinositol 3-kinase, and the gap
      junction component connexin 26 were specifically labeled. Our data demonstrate
      the potential of one specific domain of occludin, contained within 27 amino
      acids, to coordinate the binding of proteins that have been previously suggested
      to modulate TJ structure and function.

PMID- 10887181
TI  - Mutational analysis of the N-methyltransferase domain of the multifunctional
      enzyme enniatin synthetase.
AB  - N-Methylcyclopeptides like cyclosporins and enniatins are synthesized by
      multifunctional enzymes representing hybrid systems of peptide synthetases and S
      adenosyl-l-methionine (AdoMet)-dependent N-methyltransferases. The latter
      constitute a new family of N-methyltransferases sharing high homology within
      procaryotes and eucaryotes. Here we describe the mutational analysis of the N
      methyltransferase domain of enniatin synthetase from Fusarium scirpi to gain
      insight into the assembly of the AdoMet-binding site. The role of four conserved
      motifs (I, (2085)VLEIGTGSGMIL; II/Y, (2105)SYVGLDPS; IV,
      (2152)DLVVFNSVVQYFTPPEYL; and V, (2194)ATNGHFLAARA) in cofactor binding as
      measured by photolabeling was studied. Deletion of the first 21 N-terminal amino
      acid residues of the N-methyltransferase domain did not affect AdoMet binding.
      Further shortening close to motif I resulted in loss of binding activity.
      Truncation of 38 amino acids from the C terminus and also internal deletions
      containing motif V led to complete loss of AdoMet-binding activity. Point
      mutations converting the conserved Tyr(223) (corresponding to position 2106 in
      enniatin synthetase) in motif II/Y (close to motif I) into Val, Ala, and Ser,
      respectively, strongly diminished AdoMet binding, whereas conversion of this
      residue to Phe restored AdoMet-binding activity to approximately 70%, indicating
      that Tyr(223) is important for AdoMet binding and that the aromatic Tyr(223) may
      be crucial for AdoMet binding in N-methylpeptide synthetases.

PMID- 10887182
TI  - Molecular characterization of a novel intracellular hyaluronan-binding protein.
AB  - Hyaluronan has well defined functions in extracellular matrices and at the
      surface of cells. However, several studies have now shown that significant pools
      of hyaluronan are also present intracellularly, but its function therein is
      unknown. One avenue of investigation that may assist in defining the function of
      intracellular hyaluronan is to identify intracellular hyaluronan-binding
      proteins. In previous studies we identified CDC37, a cell cycle regulatory
      protein, using a monoclonal antibody that recognizes a novel group of hyaluronan
      binding proteins. In this study, we have identified a second hyaluronan-binding
      protein with this antibody and characterized its properties. This protein, which
      we have termed IHABP4, was also found to be an intracellular and a specific
      hyaluronan-binding protein, containing several hyaluronan-binding motifs:
      (R/K)[X(7)](R/K) (where R/K denotes arginine or lysine and X denotes non-acidic
      amino acids). Furthermore, we have determined the gene organization of IHABP4 and
      cloned cDNAs for the chick, mouse, and human homologs. Comparison of the deduced
      chick, mouse, and human protein sequences showed that the hyaluronan-binding
      motifs, (R/K)[X(7)](R/K), in these sequences are conserved; both chick and mouse
      IHABP4 were shown directly to bind hyaluronan. Biochemical fractionation and
      immunofluorescent localization of epitope-tagged IHABP4 indicated that it is
      mainly present in the cytoplasm. These data support the possibility that
      intracellular hyaluronan and its binding proteins may play important roles in
      cell behavior.

PMID- 10887183
TI  - Determinants of topogenesis and glycosylation of type II membrane proteins.
      Analysis of Na,K-ATPase beta 1 AND beta 3 subunits by glycosylation mapping.
AB  - The structural and molecular determinants that govern the correct membrane
      insertion and folding of membrane proteins are still ill-defined. By following
      the addition of sugar chains to engineered glycosylation sites (glycosylation
      mapping) in Na,K-ATPase beta isoforms expressed in vitro and in Xenopus oocytes,
      in combination with biochemical techniques, we have defined the C-terminal end of
      the transmembrane domain of these type II proteins. N-terminal truncation and the
      removal of a single charged residue at the N-terminal start of the putative
      transmembrane domain influence the proper positioning of the transmembrane domain
      in the membrane as reflected by a repositioning of the transmembrane domain, the
      exposure of a putative cryptic signal peptidase cleavage site, and the production
      of protein species unable to insert into the membrane. Glycosylation mapping in
      vivo revealed that the degree of glycosylation at acceptor sites located close to
      the membrane increases with the time proteins spend in the endoplasmic reticulum.
      Furthermore, core sugars added to such acceptor sites cannot be processed to
      fully glycosylated species even when the protein is transported to the cell
      surface. Thus, the glycosylation mapping strategy applied in intact cells is a
      useful tool for the study of determinants for the correct membrane insertion of
      type II and probably other membrane proteins, as well as for the processing of
      sugar chains in glycoproteins.

PMID- 10887184
TI  - Point mutants of c-raf-1 RBD with elevated binding to v-Ha-Ras.
AB  - A mutational analysis of the Ras-binding domain (RBD) of c-Raf-1 identified three
      amino acid positions (Asn(64), Ala(85), and Val(88)) where amino acid
      substitution with basic residues increases the binding of RBD to recombinant v-Ha
      Ras. The greatest increase in binding (6-9-fold) was observed with the A85K-RBD
      mutant. The elevated binding for the A85K-RBD and V88R-RBD mutants was also
      detected with Ras expressed in cultured mammalian cells, namely NIH-3T3 and BAF
      cells. None of the wild type residues in RBD positions Asn(64), Ala(85), and
      Val(88) have been previously implicated in the interaction with Ras (Block, C.,
      Janknecht, R., Herrmann, C., Nassar, N., and Wittinghofer, A. (1996) Nat. Struct.
      Biol. 3, 244-251; Nassar, N., Horn, G., Herrmann, C., Scherer, A., McCormick, F.,
      and Wittinghofer, A. (1995) Nature 375, 554-560). The discovery of elevated
      binding among the mutants in these positions implies that additional RBD residues
      can be used to generate the Ras. RBD complex. These findings are of particular
      significance in the design of Ras antagonists based on the RBD prototype. The
      A85K-RBD mutant can be used to develop an assay for measuring the level of
      activated Ras in cultured cells; Sepharose-linked A85K-RBD.GST fusion protein
      served as an activation-specific probe to precipitate Ras.GTP but not Ras.GDP
      from epidermal growth factor-stimulated cells. A85K-RBD precipitates up to 5-fold
      more Ras.GTP from mammalian cells than wild type RBD.

PMID- 10887185
TI  - Participation of Smad2, Smad3, and Smad4 in transforming growth factor beta (TGF
      beta)-induced activation of Smad7. THE TGF-beta response element of the promoter
      requires functional Smad binding element and E-box sequences for transcriptional
      regulation.
AB  - Smad7 has recently been identified as a player that antagonizes transforming
      growth factor beta (TGF-beta) signals by acting downstream of TGF-beta receptors.
      TGF-beta rapidly induces expression of Smad7 mRNA in a variety of cell types,
      suggesting participation in a negative feedback loop to control TGF-beta
      responses. We have previously described the genomic locus of rat Smad7 including
      the promoter region. Here we report polymerase chain reaction cloning of the
      corresponding promoter regions of human and murine Smad7 genes and functional
      characterization of the rat Smad7 promoter. Using transient transfection
      experiments of HepG2 cells, we identified the TGF-beta response element within a
      strongly conserved region, containing a perfect Smad binding element (SBE;
      GTCTAGAC). Performing electrophoretic mobility shift assay and cotransfection
      experiments, we were able to delineate DNA-binding complexes and identified
      Smad3, Smad4, and Smad2. Mutation of the SBE completely abolished TGF-beta
      inducibility of Smad7 in HepG2 cells, indicating that this sequence is necessary
      for TGF-beta-induced transcription. Furthermore, a 3-base pair adjacent E-box is
      additionally essential for TGF-beta-dependent promoter activation and an
      overlapping AP1 site is also involved. We conclude that regulation of Smad7
      transcription by TGF-beta is mediated via a specific constellation of recognition
      motifs localized around the SBE, which is conserved in human, rat, and murine
      genes.

PMID- 10887186
TI  - The leucine zipper of NRL interacts with the CRX homeodomain. A possible
      mechanism of transcriptional synergy in rhodopsin regulation.
AB  - Photoreceptor-specific expression of rhodopsin is mediated by multiple cis-acting
      elements in the proximal promoter region. NRL (neural retina leucine zipper) and
      CRX (cone rod homeobox) proteins bind to the adjacent NRE and Ret-4 sites,
      respectively, within this region. Although NRL and CRX are each individually able
      to induce rhodopsin promoter activity, when expressed together they exhibit
      transcriptional synergy in rhodopsin promoter activation. Using the yeast two
      hybrid method and glutathione S-transferase pull-down assays, we demonstrate that
      the leucine zipper of NRL can physically interact with CRX. Deletion analysis
      revealed that the CRX homeodomain (CRX-HD) plays an important role in the
      interaction with the NRL leucine zipper. Although binding with the CRX-HD alone
      was weak, a strong interaction was detected when flanking regions including the
      glutamine-rich and the basic regions that follow the HD were included. A
      reciprocal deletion analysis showed that the leucine zipper of NRL is required
      for interaction with CRX-HD. Two disease-causing mutations in CRX-HD (R41W and
      R90W) that exhibit reduced DNA binding and transcriptional synergy also decrease
      its interaction with NRL. These studies suggest novel possibilities for protein
      protein interaction between two conserved DNA-binding motifs and imply that cross
      talk among distinct regulatory pathways contributes to the establishment and
      maintenance of photoreceptor function.

PMID- 10887187
TI  - TWIK-2, an inactivating 2P domain K+ channel.
AB  - We cloned human and rat TWIK-2 and expressed this novel 2P domain K(+) channel in
      transiently transfected COS cells. TWIK-2 is highly expressed in the
      gastrointestinal tract, the vasculature, and the immune system. Rat TWIK-2
      currents are about 15 times larger than human TWIK-2 currents, but both exhibit
      outward rectification in a physiological K(+) gradient and mild inward
      rectification in symmetrical K(+) conditions. TWIK-2 currents are inactivating at
      depolarized potentials, and the kinetic of inactivation is highly temperature
      sensitive. TWIK-2 shows an extremely low conductance, which prevents the
      visualization of discrete single channel events. The inactivation and
      rectification are intrinsic properties of TWIK-2 channels. In a physiological
      K(+) gradient, TWIK-2 is half inhibited by 0.1 mm Ba(2+), quinine, and quinidine.
      Finally, cysteine 53 in the M1P1 external loop is required for functional
      expression of TWIK-2 but is not critical for subunit self-assembly. TWIK-2 is the
      first reported 2P domain K(+) channel that inactivates. The base-line, transient,
      and delayed activities of TWIK-2 suggest that this novel 2P domain K(+) channel
      may play an important functional role in cell electrogenesis.

PMID- 10887188
TI  - Functional characterization of a mammalian Sac1 and mutants exhibiting substrate
      specific defects in phosphoinositide phosphatase activity.
AB  - The Saccharomyces cerevisiae SAC1 gene was identified via independent analyses of
      mutations that modulate yeast actin function and alleviate the essential
      requirement for phosphatidylinositol transfer protein (Sec14p) activity in Golgi
      secretory function. The SAC1 gene product (Sac1p) is an integral membrane protein
      of the endoplasmic reticulum and the Golgi complex. Sac1p shares primary sequence
      homology with a subfamily of cytosolic/peripheral membrane phosphoinositide
      phosphatases, the synaptojanins, and these Sac1 domains define novel
      phosphoinositide phosphatase modules. We now report the characterization of a rat
      counterpart of Sac1p. Rat Sac1 is a ubiquitously expressed 65-kDa integral
      membrane protein of the endoplasmic reticulum that is found at particularly high
      levels in cerebellar Purkinje cells. Like Sac1p, rat Sac1 exhibits intrinsic
      phosphoinositide phosphatase activity directed toward phosphatidylinositol 3
      phosphate, phosphatidylinositol 4-phosphate, and phosphatidylinositol 3,5
      bisphosphate substrates, and we identify mutant rat sac1 alleles that evoke
      substrate-specific defects in this enzymatic activity. Finally, rat Sac1
      expression in Deltasac1 yeast strains complements a wide phenotypes associated
      with Sac1p insufficiency. Biochemical and in vivo data indicate that rat Sac1
      phosphatidylinositol-4-phosphate phosphatase activity, but not its
      phosphatidylinositol-3-phosphate or phosphatidylinositol-3, 5-bisphosphate
      phosphatase activities, is essential for the heterologous complementation of
      Sac1p defects in vivo. Thus, yeast Sac1p and rat Sac1 are integral membrane lipid
      phosphatases that play evolutionary conserved roles in eukaryotic cell
      physiology.

PMID- 10887189
TI  - Altered spermidine/spermine N1-acetyltransferase activity as a mechanism of
      cellular resistance to bis(ethyl)polyamine analogues.
AB  - To develop a model system to investigate mechanisms of antiproliferative action
      of bis(ethyl)polyamine analogues, intermittent analogue treatments followed by
      recovery periods in drug-free medium were used to select an N(1), N(12)
      bis(ethyl)spermine-resistant derivative of the Chinese hamster ovary cell line
      C55.7. The resulting C55.7Res line was at least 10-fold resistant to N(1),N(12)
      bis(ethyl)spermine and N(1), N(11)-bis(ethyl)norspermine. The stability of the
      resistance in the absence of selection pressure was >/=9 months, indicating that
      a heritable genotypic change was responsible for the resistance phenotype.
      Polyamine transport alterations and multi-drug resistance were eliminated as
      causes of the resistance. Spermidine/spermine N(1)-acetyltransferase (SSAT)
      activity and regulation were altered in C55.7Res cells as basal activity was
      decreased, and no activity induction resulted from exposure to analogue
      concentrations, which caused 300-fold enzyme induction in parental cells. SSAT
      mRNA levels in the absence and presence of analogue were unchanged, but no SSAT
      protein was detected in C55.7Res cells. A point mutation, which results in the
      change leucine156 (a fully conserved residue) to phenylalanine, was identified in
      the C55.7Res SSAT cDNA. Expression of wtSSAT activity in C55.7Res cells restored
      sensitivity to bis(ethyl)polyamines. These results provided definitive evidence
      that SSAT activity is a critical target of the cytotoxic action of these
      analogues.

PMID- 10887190
TI  - Identification and functional characterization of a novel subtype of neuromedin U
      receptor.
AB  - Neuromedin U is a bioactive peptide isolated originally from the porcine spinal
      cord. We recently identified neuromedin U as the cognate ligand for the orphan G
      protein-coupled receptor FM-3. In this study, we isolated cDNA coding for a novel
      G protein-coupled receptor, TGR-1, which was highly homologous with FM-3. We
      found that neuromedin U specifically and clearly elevated the extracellular
      acidification rates, arachidonic acid metabolite release, and intracellular
      Ca(2+) mobilization in Chinese hamster ovary cells expressing TGR-1. Radiolabeled
      neuromedin U specifically bound with high affinity to membrane fractions prepared
      from these cells. These results show that TGR-1, like FM-3, is a specific and
      functional receptor for neuromedin U. We analyzed TGR-1 mRNA tissue distribution
      in rats using quantitative reverse transcription-polymerase chain reaction and
      found it to considerably differ from that of FM-3 mRNA. TGR-1 mRNA was primarily
      expressed in the uterus, suggesting that TGR-1 mediates the contractile activity
      of neuromedin U in this tissue. The identification of specific and functional
      receptor subtypes for neuromedin U will facilitate the study of their
      physiological roles and the search for their specific agonists and antagonists.

PMID- 10887191
TI  - Identification and characterization of human DNA polymerase beta 2, a DNA
      polymerase beta -related enzyme.
AB  - The BRCA1 COOH terminus (BRCT) motif is present in many nuclear proteins that
      contribute to cell cycle regulation or DNA repair. Polymerase chain reaction
      based screening with degenerate primers targeted to the BRCT motif resulted in
      the isolation of a human cDNA for a previously unidentified DNA polymerase
      (designated DNA polymerase beta2) that is closely related to DNA polymerase beta
      (Pol beta). The predicted Pol beta2 protein contains a BRCT motif in its NH(2)
      terminal region; its COOH-terminal region exhibits 33% sequence identity to a
      corresponding region of human Pol beta. The Pol beta2 gene is expressed in a
      tissue-specific manner, with transcripts being most abundant in testis. A fusion
      construct comprising Pol beta2 and green fluorescent protein exhibited a
      predominantly nuclear localization in transfected HeLa cells. Recombinant human
      Pol beta2 from insect cells exhibited substantial DNA polymerase activity, but it
      did not possess terminal deoxyribonucleotidyl transferase activity. A truncated
      Pol beta2 mutant lacking the BRCT motif retained substantial DNA polymerase
      activity, whereas a mutant Pol beta2 with two alanine point mutations within the
      DNA polymerase active site did not. These results indicate that Pol beta2 is a
      Pol beta-related DNA polymerase with a BRCT motif that is dispensable for its
      polymerase activity.

PMID- 10887192
TI  - Targeted phosphorylation of inositol 1,4,5-trisphosphate receptors selectively
      inhibits localized Ca2+ release and shapes oscillatory Ca2+ signals.
AB  - The current study provides biochemical and functional evidence that the targeting
      of protein kinase A (PKA) to sites of localized Ca(2+) release confers rapid,
      specific phosphoregulation of Ca(2+) signaling in pancreatic acinar cells.
      Regulatory control of Ca(2+) release by PKA-dependent phosphorylation of inositol
      1,4, 5-trisphosphate (InsP(3)) receptors was investigated by monitoring Ca(2+)
      dynamics in pancreatic acinar cells evoked by the flash photolysis of caged
      InsP(3) prior to and following PKA activation. Ca(2+) dynamics were imaged with
      high temporal resolution by digital imaging and electrophysiological methods. The
      whole cell patch clamp technique was used to introduce caged compounds and to
      record the activity of a Ca(2+)-activated Cl(-) current. Photolysis of low
      concentrations of caged InsP(3) evoked Cl(-) currents that were inhibited by
      treatment with dibutryl-cAMP or forskolin. In contrast, PKA activators had no
      significant inhibitory effect on the activation of Cl(-) current evoked by
      uncaging Ca(2+) or by the photolytic release of higher concentrations of InsP(3).
      Treatment with Rp-adenosine-3',5'-cyclic monophoshorothioate, a selective
      inhibitor of PKA, or with Ht31, a peptide known to disrupt the targeting of PKA,
      largely abolished forskolin-induced inhibition of Ca(2+) release. Further
      evidence for the targeting of PKA to the sites of Ca(2+) mobilization was
      revealed using immunocytochemical methods demonstrating that the R(IIbeta)
      subunit of PKA was localized to the apical regions of acinar cells and co
      immunoprecipitated with the type III but not the type I or type II InsP(3)
      receptors. Finally, we demonstrate that the pattern of signaling evoked by
      acetylcholine can be converted to one that is more "CCK-like" by raising cAMP
      levels. Our data provide a simple mechanism by which distinct oscillatory Ca(2+)
      patterns can be shaped.

PMID- 10887193
TI  - Mitochondrial F(0)F(1) ATP synthase. Subunit regions on the F1 motor shielded by
      F(0), Functional significance, and evidence for an involvement of the unique F(0)
      subunit F(6).
AB  - Studies reported here were undertaken to gain greater molecular insight into the
      complex structure of mitochondrial ATP synthase (F(0)F(1)) and its relationship
      to the enzyme's function and motor-related properties. Significantly, these
      studies, which employed N-terminal sequence, mass spectral, proteolytic,
      immunological, and functional analyses, led to the following novel findings.
      First, at the top of F(1) within F(0)F(1), all six N-terminal regions derived
      from alpha + beta subunits are shielded, indicating that one or more F(0)
      subunits forms a "cap." Second, at the bottom of F(1) within F(0)F(1), the N
      terminal region of the single delta subunit and the C-terminal regions of all
      three alpha subunits are shielded also by F(0). Third, and in contrast, part of
      the gamma subunit located at the bottom of F(1) is already shielded in F(1),
      indicating that there is a preferential propensity for interaction with other
      F(1) subunits, most likely delta and epsilon. Fourth, and consistent with the
      first two conclusions above that specific regions at the top and bottom of F(1)
      are shielded by F(0), further proteolytic shaving of alpha and beta subunits at
      these locations eliminates the capacity of F(1) to couple a proton gradient to
      ATP synthesis. Finally, evidence was obtained that the F(0) subunit called
      "F(6)," unique to animal ATP synthases, is involved in shielding F(1). The
      significance of the studies reported here, in relation to current views about ATP
      synthase structure and function in animal mitochondria, is discussed.

PMID- 10887194
TI  - Characterization of native and recombinant falcipain-2, a principal trophozoite
      cysteine protease and essential hemoglobinase of Plasmodium falciparum.
AB  - Trophozoites of the malaria parasite Plasmodium falciparum hydrolyze erythrocyte
      hemoglobin in an acidic food vacuole to provide amino acids for parasite protein
      synthesis. Cysteine protease inhibitors block hemoglobin degradation, indicating
      that a cysteine protease plays a key role in this process. A principal
      trophozoite cysteine protease was purified by affinity chromatography. Sequence
      analysis indicated that the protease is encoded by a previously unidentified
      gene, falcipain-2. Falcipain-2 was predominantly expressed in trophozoites, was
      concentrated in food vacuoles, and was responsible for at least 93% of
      trophozoite soluble cysteine protease activity. A construct encoding mature
      falcipain-2 and a small portion of the prodomain was expressed in Escherichia
      coli and refolded to active enzyme. Specificity for the hydrolysis of peptide
      substrates by native and recombinant falcipain-2 was very similar, and optimal at
      acid pH in a reducing environment. Under physiological conditions (pH 5.5, 1 mm
      glutathione), falcipain-2 hydrolyzed both native hemoglobin and denatured globin.
      Our results suggest that falcipain-2 can initiate cleavage of native hemoglobin
      in the P. falciparum food vacuole, that, following initial cleavages, the
      protease plays a key role in rapidly hydrolyzing globin fragments, and that a
      drug discovery effort targeted at this protease is appropriate.

PMID- 10887195
TI  - Domain analysis of an archaeal RadA protein for the strand exchange activity.
AB  - Archaeal RadA, like eukaryotic Rad51 and bacterial RecA, promotes strand exchange
      between DNA strands with homologous sequences in vitro and is believed to
      participate in the homologous recombination in cells. The amino acid sequences of
      the archaeal RadA proteins are more similar to the eukaryotic Rad51s rather than
      the bacterial RecAs, and the N-terminal region containing domain I is conserved
      among the RadA and Rad51 proteins but is absent from RecA. To understand the
      structure-function relationship of RadA, we divided the RadA protein from
      Pyrococcus furiosus into two parts, the N-terminal one-third (RadA-n) and the
      residual C-terminal two-thirds (RadA-c), the latter of which contains the central
      core domain (domain II) of the RecA/Rad51 family proteins. RadA-c had the DNA
      dependent ATPase activity and the strand exchange activity by itself, although
      much weaker (10%) than that of the intact RadA. These activities of RadA-c were
      restored to 60% of those of RadA by addition of RadA-n, indicating that the
      proper active structure of RadA was reconstituted in vitro. These results suggest
      that the basic activities of the RecA/Rad51 family proteins for homologous
      recombination are derived from domain II, and the N-terminal region may help to
      enhance the catalytic efficiencies.

PMID- 10887196
TI  - Stabilization of eukaryotic initiation factor 4E binding to the mRNA 5'-Cap by
      domains of eIF4G.
AB  - The eukaryotic cap-binding complex eIF4F is an essential component of the
      translational machinery. Recognition of the mRNA cap structure through its
      subunit eIF4E is a requirement for the recruitment of other translation
      initiation factors to the mRNA 5'-end and thereby for the attachment of the 40 S
      ribosomal subunit. In this study, we have investigated the mechanistic basis of
      the observation that eIF4E binding to the cap is enhanced in the presence of the
      large eIF4F subunit, eIF4G. We show that eIF4E requires access to both the mRNA
      5'-cap and eIF4G to form stable complexes with short RNAs. This stabilization can
      be achieved using fragments of eIF4G that contain the eIF4E binding site but not
      the RNA recognition motifs. Full-length eIF4G is shown to induce increased eIF4E
      binding to cap analogues that do not contain an RNA body. Both results show that
      interaction of eIF4G with the mRNA is not necessary to enhance cap binding by
      eIF4E. Moreover, we show that the effect of binding of full-length eIF4G on the
      cap affinity of eIF4E can be further modulated through binding of Pab1 to eIF4G.
      These data are consistent with a model in which heterotropic cooperativity
      underlies eIF4F function.

PMID- 10887197
TI  - Molecular characterization of FMN1, the structural gene for the monofunctional
      flavokinase of Saccharomyces cerevisiae.
AB  - Flavokinase catalyzes the transfer of the gamma-phosphoryl group of ATP to
      riboflavin to form the flavocoenzyme FMN. Consistent patterns of sequence
      similarities have identified the open reading frame of unknown function YDR236c
      as a candidate to encode flavokinase in Saccharomyces cerevisiae. In order to
      determine whether the product of this gene corresponds to yeast flavokinase, its
      coding region was amplified from S. cerevisiae genomic DNA by polymerase chain
      reaction and expressed in Escherichia coli. The purified form of the expressed
      recombinant protein efficiently catalyzed the formation of FMN from riboflavin
      and ATP. In contrast to bifunctional prokaryotic flavokinase/FAD synthetase
      enzymes, the yeast enzyme did not show accompanying FAD synthetase activity.
      Deletion of YDR236c produced yeast mutants unable to grow on rich medium;
      however, the growth of the ydr236cDelta mutants could be rescued by the addition
      of FMN to the medium. Overexpression of YDR236c caused a 50-fold increase in
      flavokinase specific activity in yeast cells. These findings demonstrate that
      YDR236c corresponds to the gene encoding a monofunctional flavokinase in yeast,
      which we propose to be designated as FMN1. The FMN1 gene codes for a 25-kDa
      protein with characteristics of signals for import into mitochondria. By
      immunoblotting analysis of Saccharomyces subcellular fractions, we provide
      evidence that the Fmn1 protein is localized in microsomes and in mitochondria.
      Analysis of submitochondrial fractions revealed that the mitochondrial form of
      Fmn1p is an integral protein of the inner membrane exposing its COOH-terminal
      domain to the matrix space. A similarity search in the data base banks revealed
      the presence of sequences homologous to yeast flavokinase in the genome of
      several eukaryotic organisms such as Schizosaccharomyces pombe, Arabidopsis
      thaliana, Drosophila melanogaster, Caenorhabditis elegans, and humans.

PMID- 10887198
TI  - Three loops of the common gamma chain ectodomain required for the binding of
      interleukin-2 and interleukin-7.
AB  - The common gamma chain (gammac), a subunit of the interleukin (IL)-2, IL-4, IL-7,
      IL-9, and IL-15 receptors, contributes to both cytokine binding and subsequent
      signal transduction. Using a model-based site-directed mutagenesis strategy, we
      have identified residues of the mouse gammac extracellular domain that are
      required for normal gammac-dependent enhancement of IL-2 and IL-7 binding. One of
      these sites, Tyr-103, is homologous to key ligand-interacting residues in the
      growth hormone and erythropoietin receptors, whereas Cys-161, Cys-210, and Gly
      211 may function indirectly by maintaining the functional conformation of gammac
      via formation of an intramolecular disulfide bond. These two cysteines are also
      required for the integrity of a putative epitope recognized by TUGm2, an
      antagonistic monoclonal antibody that blocks gammac-dependent cytokine binding
      and bioactivity. These results are consistent with the involvement of three
      predicted loops in gammac that contribute to the binding of both IL-2 and IL-7.
      Mutations in these loops have also been noted in the gammac gene of patients with
      X-linked severe combined immunodeficiency.

PMID- 10887199
TI  - The biosynthesis of A2E, a fluorophore of aging retina, involves the formation of
      the precursor, A2-PE, in the photoreceptor outer segment membrane.
AB  - The autofluorescent lipofuscin that accumulates in retinal pigment epithelial
      cells with age may contribute to an age-related decline in cell function. The
      major lipofuscin fluorophore, A2E, is a pyridinium bisretinoid. We previously
      proposed that the biogenesis of A2E involves the following: (i) formation of the
      Schiff base, N-retinylidene phosphatidylethanolamine from all-trans-retinal and
      phosphatidylethanolamine in the photoreceptor outer segment membrane; (ii)
      further reaction of N-retinylidene phosphatidylethanolamine with retinal to yield
      phosphatidylethanolamine-bisretinoid, A2-PE; (iii) hydrolysis of A2-PE to
      generate A2E. To provide evidence for this biogenic scheme, all-trans-retinal was
      reacted with dipalmitoyl-l-alpha-phosphatidylethanolamine to yield DP-A2-PE (A2
      PE), as confirmed by UV, with mass spectrometry revealing the molecular ion at
      m/z 1222.9 (C(77)H(124)O(8)PN) accompanied by product ion at m/z 672.8,
      representing the phosphoryl-A2E fragment of A2-PE. In reaction mixtures of
      retinal and outer segments and in samples of Royal College of Surgeons rat retina
      containing outer segment membranous debris, A2-PE was detected as a series of
      high performance liquid chromatography peaks, each with UV similar to reference
      A2-PE. By mass spectrometry, A2-PE consisted of multiple peaks, representing
      fatty acids with different chain lengths, and the phosphoryl-A2E moiety, m/z 673.
      Incubation of the retinal/outer segment reaction mixture with phospholipase D
      generated A2E, as detected by high performance liquid chromatography, thus
      confirming A2-PE as the A2E precursor.

PMID- 10887201
TI  - Negative regulation of the nuclear factor kappa B-inducing kinase by a cis-acting
      domain.
AB  - Nuclear factor kappaB (NF-kappaB)-inducing kinase (NIK) participates in the
      activation of NF-kappaB, a family of eukaryotic transcription factors that
      mediate cell growth and transformation. NIK activates the IkappaB kinase both in
      vivo and in vitro, although how the activity of NIK is regulated has remained
      unclear. Here we show that the N-terminal region of NIK contains a negative
      regulatory domain (NRD), which is composed of a basic motif and a proline-rich
      repeat motif. Deletion of these motifs leads to a marked enhancement of NIK
      function. We further demonstrate that the N-terminal NRD interacts with the C
      terminal region of NIK, thereby inhibiting the binding of NIK to its substrate
      IkappaB kinase. Consistently, when expressed alone, the NRD potently inhibits NIK
      mediated NF-kappaB signaling. These results provide a new insight into the
      mechanism of NIK regulation.

PMID- 10887202
TI  - Characterization of Alzheimer's beta -secretase protein BACE. A pepsin family
      member with unusual properties.
AB  - The cerebral deposition of amyloid beta-peptide is an early and critical feature
      of Alzheimer's disease. Amyloid beta-peptide is released from the amyloid
      precursor protein by the sequential action of two proteases, beta-secretase and
      gamma-secretase, and these proteases are prime targets for therapeutic
      intervention. We have recently cloned a novel aspartic protease, BACE, with all
      the known properties of beta-secretase. Here we demonstrate that BACE is an N
      glycosylated integral membrane protein that undergoes constitutive N-terminal
      processing in the Golgi apparatus. We have used a secreted Fc fusion-form of BACE
      (BACE-IgG) that contains the entire ectodomain for a detailed analysis of
      posttranslational modifications. This molecule starts at Glu(46) and contains
      four N-glycosylation sites (Asn(153), Asn(172), Asn(223), and Asn(354)). The six
      Cys residues in the ectodomain form three intramolecular disulfide linkages
      (Cys(216)-Cys(420), Cys(278)-Cys(443), and Cys(330)-Cys(380)). Despite the
      conservation of the active site residues and the 30-37% amino acid homology with
      known aspartic proteases, the disulfide motif is fundamentally different from
      that of other aspartic proteases. This difference may affect the substrate
      specificity of the enzyme. Taken together, both the presence of a transmembrane
      domain and the unusual disulfide bond structure lead us to conclude that BACE is
      an atypical pepsin family member.

PMID- 10887203
TI  - Purification and enzymic properties of Mot1 ATPase, a regulator of basal
      transcription in the yeast Saccharomyces cerevisiae.
AB  - The 1867-residue Mot1 protein is a member of a superfamily of ATPases, some of
      which are helicases, that interact with protein-nucleic acid assemblies. Mot1 is
      an essential regulator of RNA polymerase II-dependent transcription in vivo and
      dissociates TATA box-binding protein (TBP)-DNA complexes in vitro. Mot1-(His)(6)
      was purified to apparent homogeneity from yeast extracts. The preparation
      efficiently dissociated TBP.TATA complexes, suggesting that no other protein or
      cofactor is required. Mot1 behaved as a non-globular monomer in hydrodynamic
      studies, and no association was detected between differentially tagged co
      expressed Mot1 constructs. ATPase activity was stimulated about 10-fold by high
      ionic strength or alkaline pH, or by deletion of the N-terminal TBP-binding
      segment, suggesting that the N-terminal domain negatively regulates the C
      terminal ATPase domain (Mot1C). Correspondingly, at moderate salt concentration,
      Mot1 ATPase (but not Mot1C) was stimulated >/=10-fold by yeast TBP, suggesting
      that interaction with TBP relieves a conformational constraint in Mot1. Double-
      or single-stranded TATA-containing DNA did not affect ATPase activity of Mot1 or
      Mot1C, with or without TBP. Mot1 did not exhibit detectable helicase activity in
      strand displacement assays using substrates with flush ends or 5'- or 3'
      overhangs. Mot1-catalyzed dissociation of TBP from DNA was not prevented by a
      psoralen cross-link positioned immediately preceding the TATA sequence. Thus,
      Mot1 most likely promotes release of TBP from TATA-containing DNA by causing a
      structural change in TBP itself, rather than by strand unwinding.

PMID- 10887204
TI  - Inhibitory effects of nitric oxide and nitrosative stress on dopamine-beta
      hydroxylase.
AB  - Dopamine-beta-hydroxylase (DbetaH) is a copper-containing enzyme that uses
      molecular oxygen and ascorbate to catalyze the addition of a hydroxyl group on
      the beta-carbon of dopamine to form norepinephrine. While norepinephrine causes
      vasoconstriction following reflex sympathetic stimulation, nitric oxide (NO)
      formation results in vasodilatation via a guanylyl cyclase-dependent mechanism.
      In this report, we investigated the relationship between NO and DbetaH enzymatic
      activity. In the initial in vitro experiments, the activity of purified DbetaH
      was inhibited by the NO donor, diethylamine/NO (DEA/NO), with an IC(50) of 1 mm.
      The inclusion of either azide or GSH partially restored DbetaH activity,
      suggesting the involvement of the reactive nitrogen oxide species, N(2)O(3).
      Treatment of human neuroblastoma cells (SK-N-MC) with diethylamine/NO decreased
      cellular DbetaH activity without affecting their growth rate and was augmented by
      the depletion of intracellular GSH. Co-culture of the SK-N-MC cells with
      interferon-gamma and lipopolysaccharide-activated macrophages, which release NO,
      also reduced the DbetaH activity in the neuroblastoma cells. Our results are
      consistent with the hypothesis that nitrosative stress, mediated by N(2)O(3), can
      result in the inhibition of norepinephrine biosynthesis and may contribute to the
      regulation of neurotransmission and vasodilatation.

PMID- 10887205
TI  - Analysis of PDZ domain-ligand interactions using carboxyl-terminal phage display.
AB  - PDZ domains mediate protein-protein interactions at specialized subcellular
      sites, such as epithelial cell tight junctions and neuronal post-synaptic
      densities. Because most PDZ domains bind extreme carboxyl-terminal sequences, the
      phage display method has not been amenable to the study of PDZ domain binding
      specificities. For the first time, we demonstrate the functional display of a
      peptide library fused to the carboxyl terminus of the M13 major coat protein. We
      used this library to analyze carboxyl-terminal peptide recognition by two PDZ
      domains. For each PDZ domain, the library provided specific ligands with sub
      micromolar binding affinities. Synthetic peptides and homology modeling were used
      to dissect and rationalize the binding interactions. Our results establish
      carboxyl-terminal phage display as a powerful new method for mapping PDZ domain
      binding specificity.

PMID- 10887207
TI  - Mechanisms of DNA double-strand break repair and their potential to induce
      chromosomal aberrations.
AB  - DNA double-strand breaks (DSB) are considered to be critical primary lesions in
      the formation of chromosomal aberrations. DSB may be induced by exogenous agents,
      such as ionizing radiation, but also occur spontaneously during cellular
      processes at quite significant frequencies. To repair this potentially lethal
      damage, eukaryotic cells have evolved a variety of repair pathways related to
      homologous and illegitimate recombination, also called non-homologous DNA end
      joining, which may induce small scale mutations and chromosomal aberrations. In
      this paper we review the major cellular sources of spontaneous DSB and the
      different homologous and illegitimate recombination repair pathways, with
      particular focus on their potential to induce chromosomal aberrations.

PMID- 10887206
TI  - Functional interaction between the HIV transactivator Tat and the transcriptional
      coactivator PC4 in T cells.
AB  - The human immunodeficiency virus (HIV) transactivator Tat is a potent activator
      of transcription from the HIV long terminal repeat and is essential for efficient
      viral gene expression and replication. Tat has been shown to interact with
      components of the basal transcription machinery and transcriptional activators.
      Here we identify the cellular coactivator PC4 as a Tat-interacting protein using
      the yeast two-hybrid system and confirmed this interaction both in vitro and in
      vivo by coimmunoprecipitation. We found that this interaction has a functional
      outcome in that PC4 overexpression enhanced activation of the HIV long terminal
      repeat in transient transfection studies in a Tat-dependent manner. The domains
      of PC4 and Tat required for the interaction were mapped. In vitro binding studies
      showed that the basic transactivation-responsive binding domain of Tat is
      required for the interaction with PC4. The minimum region of PC4 required for Tat
      binding was amino acids 22-91, whereas mutation of the lysine-rich domain between
      amino acids 22 and 43 prevented interaction with Tat. Tat-PC4 interactions may be
      controlled by phosphorylation, because phosphorylation of PC4 by casein kinase II
      inhibited interactions with Tat both in vivo and in vitro. We propose that PC4
      may be involved in linking Tat to the basal transcription machinery.

PMID- 10887208
TI  - Spontaneous and X-ray-induced chromosomal aberrations in Werner syndrome cells
      detected by FISH using chromosome-specific painting probes.
AB  - Werner syndrome (WS) is a rare autosomal disorder characterized by premature
      aging exhibiting chromosome instability and predisposition to cancer. Cells
      derived from WS patients show a variety of constitutionally stable chromosomal
      aberrations as detected by conventional chromosome banding techniques. We have
      employed the fluorescence in situ hybridization (FISH) technique using painting
      probes for 12 different chromosomes to detect stable chromosome exchanges in
      three WS cell lines and three control cell lines. WS cell lines showed increased
      frequencies of both stable and unstable chromosome aberrations detected by FISH
      and Giemsa staining, respectively. One WS lymphoblastoid cell line (KO375) had a
      5/12 translocation in all the cells and approximately 60% of the cells had an
      additional translocated chromosome 12. A high frequency of aneuploid cells was
      found in all the WS cell lines studied. Though WS cells are known to be
      chromosomally unstable, unlike other chromosome instability syndromes they are
      not sensitive to mutagenic agents. We studied the frequencies of X-ray-induced
      chromosomal aberrations in two WS cell lines and found an approximately 60%
      increase in the frequencies of fragments and no consistent increase in the
      frequencies of exchanges.

PMID- 10887210
TI  - A comparison of mutation spectra detected by the Escherichia coli lac(+)
      reversion assay and the Salmonella typhimurium his(+) reversion assay.
AB  - Each of the Escherichia coli tester strains in the WP3101P-WP3106P series
      contains an F' plasmid with a different base substitution mutation within the
      lacZ gene. Each of the six possible base substitution mutations, therefore, can
      be assayed with these strains by Lac(+) reversion. We used the strains to
      characterize the mutational profiles of 21 chemical mutagens, including
      alkylating agents, base analogs and oxidative compounds. We also assayed the
      mutagens with Salmonella typhimurium tester strains TA7002, TA7004 and TA7005,
      which detect A.T-->T.A, G.C-->A.T and G.C-->T.A mutations, respectively, and we
      compared the sensitivity and specificity of the two systems. Escherichia coli
      strain WP3102P was more sensitive than the S.TYPHIMURIUM: strains to G.C-->A.T
      transitions induced by N(4)-aminocytidine, 5-azacytidine, cumene hydroperoxide
      (CHP), t-butyl hydroperoxide (BHP), N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG),
      methyl methane sulfonate and N-ethyl-N-nitrosourea (ENU), while the reverse was
      true for G.C-->A.T transitions induced by 2-aminopurine and phosmet. Escherichia
      coli strain WP3104P, which detects G.C-->T.A transversions, was superior to the
      S.TYPHIMURIUM: strains in detecting transversions induced by N(4)-aminocytidine,
      5-azacytidine, 5-diazouracil, CHP, BHP, ENNG, ENU, 4-nitroquinoline 1-oxide (4
      NQO) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). Escherichia
      coli WP3105P was also more sensitive than S. TYPHIMURIUM: to A.T-->T.A
      transversions induced by N-methyl-N- nitrosourea (MNU), CHP and 4-NQO, but it was
      less sensitive to those induced by ENNG, ENU and 2-aminopurine. The present
      results indicate that the E.COLI: Lac(+) reversion system with tester strains
      WP3101P-WP3106P is as sensitive as the S.TYPHIMURIUM: His(+) reversion system for
      the detection of specific mutations induced by a variety of direct mutagens.

PMID- 10887209
TI  - The role of glutathione in DNA damage by potassium bromate in vitro.
AB  - We have investigated the role of reduced glutathione (GSH) in the genetic
      toxicity of the rodent renal carcinogen potassium bromate (KBrO(3)). A
      statistically significant increase in the concentration of 8-oxodeoxyguanosine (8
      oxodG) relative to deoxyguanosine was measured following incubation of calf
      thymus DNA with KBrO(3) and GSH or N-acetylcysteine (NACys). This was dependent
      on these thiols and was associated with the loss of GSH and production of
      oxidized glutathione. A short-lived (<6 min) intermediate was apparent which did
      not react with the spin trap dimethylpyrroline N-oxide. DNA oxidation was not
      evident when potassium chlorate (KClO(3)) or potassium iodate (KIO(3)) were used
      instead of KBrO(3), though GSH depletion also occurred with KIO(3), but not with
      KClO(3). Other reductants and thiols in combination with KBrO(3) did not cause a
      significant increase in DNA oxidation. DNA strand breakage was also induced by
      KBrO(3) in human white blood cells (5 mM) and rat kidney epithelial cells (NRK
      52E, 1.5 mM). This was associated with an apparent small depletion of thiols in
      NRK-52E cells at 15 min and with an elevation of 8-oxodG at a delayed time of 24
      h. Depletion of intra-cellular GSH by diethylmaleate in human lymphocytes
      decreased the amount of strand breakage induced by KBrO(3). Extracellular GSH,
      however, protected against DNA strand breakage by KBrO(3), possibly due to the
      inability of the reactive product to enter the cell. In contrast, membrane
      permeant NACys enhanced KBrO(3)-induced DNA strand breakage in these cells. DNA
      damage by KBrO(3) is therefore largely dependent on access to intracellular GSH.

PMID- 10887211
TI  - A new approach to evaluate mechanistic relationships among genotoxic phenomena:
      validation.
AB  - In order to determine its applicability for the study of genotoxicity, a recently
      developed method to probe for possible mechanistic relationships among
      toxicological phenomena was applied to the induction of mutations in Salmonella
      typhimurium. Since the basis of this phenomenon is understood, this would provide
      a test of the applicability of the new method to DNA-based mechanisms. The
      results presented indicate that significant relationships are indeed found among
      phenomena involving damage to or modification of DNA but not between them and non
      genotoxic phenomena. The present results suggest that the newly developed
      approach could be applied to test mechanistic hypotheses involving genotoxic
      phenomena.

PMID- 10887212
TI  - A mathematical model of the in vitro micronucleus assay predicts false negative
      results if micronuclei are not specifically scored in binucleated cells or in
      cells that have completed one nuclear division.
AB  - A mathematical model is described that predicts the effect of altered
      nuclear/cell division kinetics and cytotoxicity on micronucleus expression in
      vitro when the micronucleus assay is performed without discriminating between
      cells that have divided once and cells that have not divided after genotoxic
      insult. The model is based on the probabilities of: (i) a viable cell completing
      nuclear division; (ii) micronucleus expression in a cell that completes nuclear
      division after genotoxic insult; (iii) a cell not dividing and surviving as a
      mononuclear cell; (iv) a cell dying by necrosis or apoptosis. The model predicts:
      (i) false negative results for relatively weak chromosome damaging agents that
      also inhibit nuclear division, if micronuclei are scored in mononucleated cells
      without discriminating between divided and non-divided cells; (ii) this tendency
      for a false negative result when scoring micronuclei without discriminating
      between non-divided and once-divided mononuclear cells increases with cell lines
      and culture conditions that do not result in optimal rates of nuclear division
      (i.e. >90% of dividing cells); (iii) the absolute increment in micronucleus
      frequency in binucleated cells is at least 2-fold greater than that observed in
      mononucleated cells when nuclear division is not inhibited and this difference
      increases with increasing nuclear inhibition. The number of dead cells does not
      influence the micronucleus frequency if only viable cells are considered when
      determining the micronucleus frequency ratio. The results from this model suggest
      that the micronucleus assay when performed by scoring mononucleated cells,
      without restricting the score to those cells that have divided once after
      genotoxic insult, is prone to produce false negative results and, therefore,
      cannot be considered reliable or conclusive. Scoring of micronuclei in
      cytokinesis-blocked binucleated cells is predicted by the model to provide
      consistent results under all culture conditions and based on these theoretical
      results should be considered the preferred choice.

PMID- 10887213
TI  - Induction of an adaptive response in Drosophila imaginal disc cells exposed in
      vivo to low doses of alkylating agents.
AB  - The adaptive response of Drosophila larvae to three alkylating agents (ethyl
      methanesulfonate, methyl methanesulfonate and N-nitroso-N-ethylurea) has been
      studied in the wing spot test. The experimental procedure included a 24 h
      pretreatment of 2-day-old larvae with two different adaptive doses followed by a
      challenge dose applied until the end of development. The genotoxic effects were
      analysed in trans-heterozygous larvae for the third chromosome recessive markers
      multiple wing hairs (mwh) and flare (flr(3)). Genetic changes induced in somatic
      cells of the wing imaginal discs led to loss of heterozygosity, expressed as
      mutant clones of the genetic markers used. From our results it appears that the
      adaptive doses clearly reduce the frequency of mutant clones induced by the
      challenge dose. As far as we know, this is the first time that the existence of
      an adaptive response to alkylating agents after Drosophila larval treatment has
      been reported using the wing spot assay.

PMID- 10887214
TI  - Clastogenic effects of two tyrosine kinase inhibitors, tyrphostin 23 and
      tyrphostin 46, on a transformed (CHO-K1) and on a primary embryonic chinese
      hamster cell line (CHE).
AB  - Protein tyrosine kinases (PTKs) play fundamental roles in signal transduction
      pathways. Many proliferative diseases are characterized by deregulation of PTK
      activity, therefore PTKs appear as promising targets in the design of anticancer
      drugs. Tyrphostins are a family of synthetic compounds which efficiently target
      specific PTKs without competing for ATP and thus are much less cytotoxic with
      respect to conventional therapeutic agents. We tested two tyrphostin derivatives,
      Tyrphostin 23 and Tyrphostin 46, on a transformed (CHO-K1) and on a primary
      embryonic Chinese hamster cell line (CHE) to determine whether these compounds
      had a genotoxic effect. We found that the tyrphostins increased sister chromatid
      exchange frequency in both cell lines, but induced chromosomal aberrations only
      in the transformed CHO-K1 cell line when treatment was in the S phase of the cell
      cycle, and not in primary CHE cells. Such a result could have important
      therapeutic implications: it could mean that deregulation of signal transduction
      pathways in cells which already have a deficit in cell cycle control could cause
      chromosomal aberrations.

PMID- 10887215
TI  - Detection and characterization of micronuclei in a murine liver epithelial cell
      line, by application of the in vitro cytokinesis block MN assay and PRINS.
AB  - The cytokinesis block micronucleus assay was applied to murine cell line C6,
      derived from fetal liver, after an optimal protocol had been designed.
      Micronucleus frequencies were assayed after exposure to three concentrations of
      colcemid or diepoxybutane. Two-colour primed in situ DNA synthesis (PRINS) was
      applied to simultaneously label telomeric and centromeric (minor satellite DNA)
      sequences. Both chemicals induced a highly significant increase in MN and the
      effect was dose dependent. Diepoxybutane did not appear to significantly increase
      the frequency of centromere-positive micronuclei. Colcemid, as expected, induced
      high frequencies of centromere-positive micronuclei at all concentrations tested;
      in addition a significant increase in centromere-negative micronuclei was
      observed at 10(-5) M. Many centromere-positive micronuclei carried three or four
      telomeres, thus indicating that a duplicated (non-disjoined) chromosome with two
      chromatids was contained in the micronucleus. This observation leads to the
      conclusion that micronuclei deriving from missegregation could be due to errors
      occurring before the onset of anaphase. The results obtained on C6 cells are in
      good agreement with those obtained on other cell systems, indicating that this
      cell line can be considered for in vitro aneuploidy evaluation.

PMID- 10887216
TI  - Sequence analysis of the boundaries of the tandem duplication from the white
      ivory mutant of Drosophila melanogaster and two chemically induced revertants.
AB  - We have previously shown that revertants obtained from the white-ivory mutants of
      Drosophila melanogaster, both spontaneous and induced, have lost a DNA fragment
      of 2.9 kb that is duplicated in tandem in the white-ivory mutation. To prove the
      accuracy of the deletion in revertants obtained after treatment with alkylating
      agents, we have sequenced DNA fragments previously amplified by PCR. These
      fragments correspond to the ends of the remaining 2.9 kb copy of these revertants
      and the internal region of the junction of both copies, which constitutes the
      duplication in the white-ivory mutant. These sequences are compared with those
      from white-ivory mutants. Our results show slight differences from the published
      sequence of the white-ivory mutation and with the wild-type sequence of the white
      locus. The sequences of the two revertants analysed show that excision of the
      duplicated fragment is very precise. We hypothesize the mechanism of excision in
      terms of intrachromosomal recombination induced by double-strand break repair
      after treatment with alkylating agents.

PMID- 10887217
TI  - Induction of apoptosis and inhibition of signalling pathways by alkylated
      purines.
AB  - Addition of growth factors such as EGF and insulin to serum-starved G(0) Chinese
      hamster fibroblast cells results in activation of the phosphatidylinositol 3
      kinase (PI3-K)/p70 S6 kinase (p70(S6K)) pathway and the ras-raf mitogen-activated
      kinase (MAPK) pathway. Activation of these pathways is usually associated with
      protection of cells from apoptosis. We have studied the effect of three
      alkylpurines, O(6)-methylguanine (O6meG), O(6)-ethylguanine (O6etG) and 6
      dimethylaminopurine (6DMAP) on two particular steps of these pathways, namely
      activation of p70(S6K) and of MAPK. Under the same experimental conditions we
      studied the ability of these alkylpurines to induce apoptosis. Our results show
      that the three alkylpurines induced apoptosis with increasing efficiency from
      O6meG to 6DMAP to O6etG. The induction of apoptosis was phase specific, with the
      G(0)/G(1) phase being most sensitive. A reduced apoptotic response was observed
      in cells with abnormal nuclear accumulation of mutant or wild-type p53,
      suggesting that functional p53 was required for the induction of apoptosis. At
      concentrations inducing apoptosis the three alkylpurines inhibited p70(S6K)
      activity, while they had the opposite effect on MAPK. Rapamycin, a specific
      inhibitor of the p70(S6K) pathway, did not induce apoptosis at doses inhibiting
      p70(S6K) activity, suggesting that p70(S6K) is not directly involved in
      apoptosis. As expected, and in line with results reported by others, wortmannin,
      an upstream inhibitor of the p70(S6K) pathway, did induce apoptosis. We propose
      that activation of the MAPK pathway and simultaneous inhibition of the p70(S6K)
      pathway induce an apoptotic response in the cell.

PMID- 10887218
TI  - Isolation of camptothecin-sensitive chinese hamster cell mutants: phenotypic
      heterogeneity within the ataxia telangiectasia-like XRCC8 (irs2) complementation
      group.
AB  - Using a replica microwell method, four Chinese hamster lines which exhibit
      hypersensitivity to the topoisomerase I inhibitor camptothecin, designated CM1,
      CM2, CM3 and CM6, have been isolated. Their sensitivity towards camptothecin
      varied from 3.5- to 8.2-fold with relative sensitivity as follows: CM2 < CM3 <
      CM6 < CM1. Genetic analysis of the CM mutants has established that CM1, CM3 and
      CM6 fail to complement each other and can each be assigned to the irs2 (XRCC8)
      complementation group. The mutant CM2 could not be definitively assigned to a
      complementation group because it presented a semi-dominant phenotype. In contrast
      to their sensitivity to camptothecin, the four CM mutants were less sensitive
      (1.1- to 2.2-fold) to the topoisomerase II inhibitors etoposide and adriamycin,
      although CM1, CM3 and CM6 were more sensitive (2.5- to 3. 8-fold) to
      streptonigrin (a free radical generator and a topoisomerase II inhibitor). All
      four mutant lines displayed an increased sensitivity to the bifunctional
      alkylating agent mitomycin C (2.4- to 5.1-fold). Surprisingly, given their
      assignment to the irs2 (XRCC8) complementation group, CM1, CM3 and CM6 displayed
      only a minor increase in sensitivity to ionizing radiation (1.6-fold or less).
      Similar sensitivity of these CM mutants was observed for the radiomimetic
      compound bleomycin (1.7-fold sensitive or less). This study indicates that XRCC8
      mutants are isolated at high frequency from the parent line V79 and that
      phenotypic heterogeneity amongst the irs2 (XRCC8) complementation group is
      greater than previously encountered. Mutations in different regions of the XRCC8
      gene may be responsible for the differing cellular phenotypes. Hamster XRCC8
      mutants show phenotypic similarities to cultured cells from ataxia telangiectasia
      and Nijmegen break syndrome (NBS) patients and are likely to be defective in the
      same pathway in which the ATM (ataxia telangiectasia-mutated) and the NBS genes
      operate.

PMID- 10887219
TI  - Gastrointestinal radiology in the United States: An overview of the past 50
      years.
AB  - Gastrointestinal radiology has expanded its scope beyond conventional abdominal
      radiography, barium studies, and cholecystography. Ultrasonography allows imaging
      of solid abdominal organs and the intestine without the use of radiation.
      Computed tomography now allows comprehensive assessment of abdominal and pelvic
      inflammatory and infectious processes, obstruction, tumor detection and staging,
      and display of vasculature and blunt trauma effects that were not possible 50
      years ago. Magnetic resonance imaging provides multiplanar imaging to the same
      degree, without the use of radiation. Barium studies of the gastrointestinal
      tract, enteroclysis for small-bowel assessment, and conventional radiography
      still have a role, despite the extensive use of fiberoptic endoscopy. Fluoroscopy
      is still important, but great advances in technologies have changed
      gastrointestinal radiology irrevocably.

PMID- 10887220
TI  - Charles A. Rohrmann, Jr, MD Armed Forces Institute of Pathology 2000-2001
      Distinguished Scientist.

PMID- 10887221
TI  - CT fluoroscopy: another advancement with additional challenges in radiation
      management.

PMID- 10887222
TI  - Diagnosis of colorectal neoplasms at double-contrast barium enema examination.
AB  - The double-contrast barium enema examination has been recognized as an option for
      colorectal cancer screening in Americans with average risk who are greater than
      50 years of age. The purpose of this article is to review the principles for
      diagnosing colorectal neoplasms on double-contrast images and the spectrum of
      findings associated with these lesions. Colonic polyps can be sessile or
      pedunculated; their appearance depends on whether they are located on the
      dependent or nondependent wall of the bowel. Villous tumors may be flat,
      lobulated lesions, also known as "carpet" lesions, that are characterized by a
      finely nodular or reticular surface pattern, without a discrete mass. Colonic
      carcinomas may manifest as plaquelike, polypoid, semiannular ("saddle") or
      annular lesions. Colonic neoplasms sometimes are more difficult to detect in the
      region of the ileocecal valve or the distal rectum or in patients with severe
      diverticulosis. Careful double-contrast technique and meticulous scrutiny of the
      images therefore are required to optimize detection of these lesions.

PMID- 10887223
TI  - Major salivary gland imaging.
AB  - The algorithm for imaging the salivary glands depends on the clinical scenario
      with which the patient presents to the clinician. Because of the importance of
      identifying small calculi in the gland or salivary duct as the cause of the
      symptom complex, nonenhanced computed tomography is often the best initial study
      for the evaluation of the painful gland. If an infiltrative neoplasm is highly
      suspected, nonenhanced and enhanced magnetic resonance (MR) imaging may be
      superior in demonstrating perineural, meningeal, and skull base invasion.
      Sialography is reserved for the evaluation of chronic sialadenitides unrelated to
      sialolithiasis. Thin-section MR techniques for MR sialography may soon replace
      conventional sialography.

PMID- 10887224
TI  - Award-winning papers and honored lectures

PMID- 10887225
TI  - Corticobasal degeneration: evaluation of cortical atrophy by means of hemispheric
      surface display generated with MR images.
AB  - PURPOSE: To determine the characteristics of cortical atrophy in corticobasal
      degeneration and Alzheimer disease by using a hemispheric surface display
      generated with magnetic resonance (MR) images. MATERIALS AND METHODS: The
      magnitude and extent of cortical atrophy were evaluated with MR hemispheric
      surface display and volumetric measurement in three groups: 17 patients with
      corticobasal degeneration, 17 matched patients with Alzheimer disease, and 17
      matched healthy control subjects. RESULTS: The extent and magnitude of cortical
      atrophy were larger in the group with corticobasal degeneration than in the group
      with Alzheimer disease. The parasagittal and paracentral regions were
      significantly more atrophic in patients with corticobasal degeneration than in
      patients with Alzheimer disease (P <.05). The mean hemispheric-to-total
      intracranial volume ratios were significantly smaller in the patients with
      corticobasal degeneration (61%) and those with Alzheimer disease (64%) than in
      control subjects (69%). Asymmetry of hemispheric volume was significantly larger
      in the group with corticobasal degeneration than in the control group.
      CONCLUSION: The extent of cortical atrophy in corticobasal degeneration is more
      widespread than was previously thought. Parasagittal and paracentral atrophy is a
      distinctive feature of corticobasal degeneration and distinguishes it from
      Alzheimer disease.

PMID- 10887226
TI  - Intracranial aneurysms: detection with gadolinium-enhanced dynamic three
      dimensional MR angiography-initial results.
AB  - PURPOSE: To assess the clinical utility and accuracy of contrast material
      enhanced dynamic three-dimensional (3D) T1-weighted magnetic resonance (MR)
      angiography in the detection of unruptured intracranial aneurysms. MATERIALS AND
      METHODS: A prospective blinded comparison of 3D contrast-enhanced T1-weighted MR
      angiography with 3D inflow magnetization transfer and tilted optimized
      nonsaturating excitation (MT TONE) imaging, phase-contrast MR angiography, and
      conventional digital subtraction angiography (DSA) was performed in 32
      consecutive patients. The first dynamic 3D contrast-enhanced T1-weighted
      acquisition was individually timed after injection of a bolus of gadolinium-based
      contrast agent to obtain an arterial phase image followed by two sequential
      venous phase images (three 18-second acquisitions). Two readers independently
      interpreted and graded the MR images for diagnostic confidence and depiction of
      aneurysms and subsequently compared them with DSA images. RESULTS: Three
      dimensional contrast-enhanced T1-weighted MR angiograms depicted all 23 aneurysms
      detected in 17 patients at DSA (mean size, 6 mm; range, 2-21 mm) with one false
      positive result by one reader (sensitivity, 100%; specificity, 94%). MT TONE and
      phase-contrast images failed to depict one and seven aneurysms, respectively (MT
      TONE sensitivity of 96% and specificity of 100%, phase-contrast sensitivity of
      70% and specificity of 100%). Aneurysm depiction at 3D contrast-enhanced T1
      weighted MR angiography was significantly better than that at MT TONE imaging (P
      <.012), and that with both was significantly superior to that of phase-contrast
      imaging (P <. 001). Differences in diagnostic confidence in the presence of an
      aneurysm were not significant between 3D contrast-enhanced T1-weighted and MT
      TONE imaging (P =.076). CONCLUSION: Dynamic 3D contrast-enhanced T1-weighted MR
      angiography is a fast, efficient, and minimally invasive imaging method with
      which to diagnose intracranial aneurysms.

PMID- 10887227
TI  - Superselective ophthalmic arterial fibrinolysis with urokinase for recent severe
      central retinal venous occlusion: initial experience.
AB  - PURPOSE: To investigate the effects of local ophthalmic arterial fibrinolysis on
      central retinal venous occlusion (CRVO). MATERIALS AND METHODS: Thirteen patients
      had recent severe nonischemic CRVO for which no alternative therapy was
      available. A flow-guide microcatheter was introduced coaxially via the femoral
      artery into the ophthalmic arterial ostium, and urokinase was perfused for 40
      minutes. Vision, funduscopic findings, and retinal perfusion were assessed during
      1 year of follow-up. RESULTS: Five of the 13 patients treated experienced visual
      improvement (P =.05) and retinal perfusion within 24-48 hours. Vision returned to
      normal within 24-48 hours in three patients, within 1 week in one patient, and
      within 1 month in one patient. These five patients exhibited progressive lesion
      regression within 2-4 weeks at funduscopy. Their clinical course prior to
      treatment resembled that of combined central retinal arterial occlusion (CRAO)
      and CRVO, which typically has a poor visual outcome. One patient relapsed 1 month
      after fibrinolysis. Of the remaining eight patients, one had normal vision at 12
      months, and seven had no improvement. No technical complications were observed.
      CONCLUSION: Although there was no control group, the short period between
      fibrinolysis and substantial visual improvement, combined with marked retinal
      perfusion improvement, suggests that fibrinolysis is beneficial for CRVO,
      especially for recent CRAO and CRVO.

PMID- 10887228
TI  - Inferior vena caval filters: review of a 26-year single-center clinical
      experience.
AB  - PURPOSE: To review a 26-year single-center clinical experience with inferior vena
      caval filters. MATERIALS AND METHODS: During 1973-1998, 1,765 filters were
      implanted in 1,731 patients. Hospital files were reviewed, and data were
      collected about the indications, safety, effectiveness, numbers, and types of
      caval filters. Fatal post-filter pulmonary embolism (PE) was considered the
      primary outcome. Morbidity and mortality were determined as secondary outcomes.
      Survival and morbidity-free survival curves were calculated. RESULTS: The
      prevalence of observed post-filter PE was 5.6%. It was fatal in 3.7% of patients.
      In most patients, fatal PE occurred soon after filter insertion (median, 4.0
      days; 95% CI: 2.2, 5.8 days). Major complications occurred in 0.3% of procedures.
      The prevalence of observed post-filter caval thrombosis was 2.7%. The 30-day
      mortality rate was 17.0% overall, higher among patients with neoplasms (19.5%) as
      compared with those without neoplasms (14.3%; P =.004). Filter efficacy and
      associated morbidity were not different in 46 patients with suprarenal filters.
      The rate of filters placed for prophylaxis was 4.7% overall and increased to
      16.4% in 1998. From 1980 to 1996, there was a fivefold increase in the number of
      caval filter implants. In recent years, more filters were implanted in younger
      patients. CONCLUSION: Inferior vena caval filters provide protection from life
      threatening PE, with minimal morbidity.

PMID- 10887229
TI  - Peripheral arterial disease: gadolinium-enhanced MR angiography versus color
      guided duplex US--a meta-analysis.
AB  - PURPOSE: To summarize and compare the published data on gadolinium-enhanced
      magnetic resonance (MR) angiography and color-guided duplex ultrasonography (US)
      for the work-up for peripheral arterial disease. MATERIALS AND METHODS: Studies
      published between January 1984 and November 1998 were included if (a) gadolinium
      enhanced MR angiography and/or color-guided duplex US were performed for
      evaluation of arterial stenoses and occlusions in the work-up for peripheral
      arterial disease of the lower extremities, (b) conventional angiography was the
      reference standard, and (c) absolute numbers of true-positive, false-negative,
      true-negative, and false-positive results were available or derivable. RESULTS:
      With a random effects model, pooled sensitivity for MR angiography (97.5% [95%
      CI: 95.7%, 99.3%]) was higher than that for duplex US (87.6% [95% CI: 84.4%,
      90.8%]). Pooled specificities were similar: 96.2% (95% CI: 94.4%, 97.9%) for MR
      angiography and 94.7% (95% CI: 93.2%, 96.2%) for duplex US. Summary receiver
      operating characteristic analysis demonstrated better discriminatory power for MR
      angiography than for duplex US. Regression coefficients for MR angiography versus
      US were 1.67 (95% CI: -0.23, 3.56) with adjustment for covariates, 2.11 (95% CI:
      0.12, 4.09) without such adjustment, and 1.73 (95% CI: 0.44, 3.02) with a random
      effects model. CONCLUSION: Gadolinium-enhanced MR angiography has better
      discriminatory power than does color-guided duplex US and is a highly sensitive
      and specific method, as compared with conventional angiography, for the work-up
      for peripheral arterial disease.

PMID- 10887230
TI  - Stent placement for renal arterial stenosis: where do we stand? A meta-analysis.
AB  - PURPOSE: To perform a meta-analysis of renal arterial stent placement in
      comparison with renal percutaneous transluminal angioplasty (PTA) in patients
      with renal arterial stenosis. MATERIALS AND METHODS: Studies dealing with renal
      arterial stent placement (14 articles; 678 patients) and renal PTA (10 articles;
      644 patients) published up to August 1998 were selected. A random-effects model
      was used to pool the data. RESULTS: Renal arterial stent placement proved highly
      successful, with an initial adequate performance in 98% and major complications
      in 11%. The overall cure rate for hypertension was 20%, whereas hypertension was
      improved in 49%. Renal function improved in 30% and stabilized in 38% of
      patients. The restenosis rate at follow-up of 6-29 months was 17%. Stent
      placement had a higher technical success rate and a lower restenosis rate than
      did renal PTA (98% vs 77% and 17% vs 26%, respectively; P <.001). The
      complication rate was not different between the two treatments. The cure rate for
      hypertension was higher and the improvement rate for renal function was lower
      after stent placement than after renal PTA (20% vs 10% and 30% vs 38%,
      respectively; P <.001). CONCLUSION: Renal arterial stent placement is technically
      superior and clinically comparable to renal PTA alone.

PMID- 10887231
TI  - Detection of thrombosis in the portal venous system: comparison of contrast
      enhanced MR angiography with intraarterial digital subtraction angiography.
AB  - PURPOSE: To determine whether intraarterial digital subtraction angiography (DSA)
      can be replaced by contrast material-enhanced magnetic resonance (MR) angiography
      in the assessment of patency or thrombosis of the portal venous system in
      patients with portal hypertension. MATERIALS AND METHODS: Thirty-six patients
      with portal hypertension underwent contrast-enhanced MR angiography and
      intraarterial DSA for assessment of the portal venous system. The images were
      evaluated for vessel patency or thrombosis of the portal, splenic, or superior
      mesenteric vein. RESULTS: Of the 101 vessels evaluated, 42 were thrombosed.
      Overall sensitivity, specificity, and accuracy for the detection of thrombosis
      were 100%, 98%, and 99%, respectively, for MR angiography and 91%, 100%, and 96%,
      respectively, for DSA; differences between the imaging methods were not
      statistically significant. Only in four patients with six vessels (6%) were there
      discordant findings between MR angiography and DSA. CONCLUSION: Noninvasive
      contrast-enhanced MR angiography has the potential to replace intraarterial DSA
      as the standard method to assess the whole portal venous system.

PMID- 10887232
TI  - Autologous blood clot seal to prevent pneumothorax at CT-guided lung biopsy.
AB  - PURPOSE: To determine whether the use of autologous blood clot seal (ABCS) after
      biopsy of lung lesions can reduce or prevent pneumothorax. MATERIALS AND METHODS:
      The authors evaluated 100 patients (63 men, 37 women; age range, 27-78 years)
      with pleural (n = 23) or deep (n = 77) lesions. Thirty-eight patients had
      emphysema. Patients were randomly assigned to one of two groups: those in whom
      the biopsy track was sealed with autologous blood clot (n = 50) and those who did
      not receive autologous blood clot (n = 50). Biopsy was performed with computed
      tomographic (CT) guidance and a 19-gauge coaxial system. The autologous blood
      clot, which ranged from 0.5 to 4.5 mL, was injected while the sheath was being
      withdrawn. RESULTS: Pneumothorax developed in four of the 23 patients (17%) with
      pleural lesions and 19 of the 77 patients (24%) with deep lesions. Pneumothorax
      occurred in four of the 45 patients (9%) who had deep lesions and received
      autologous blood clot and in 15 of the 32 patients (47%) who had deep lesions and
      did not receive autologous blood clot (P <.001). In patients with emphysema,
      pneumothorax occurred in three of the 20 patients (15%) who received autologous
      blood clot and 10 of the 14 (71%) who did not (P <.001). There were seven large
      pneumothoraces necessitating treatment; all occurred in patients who did not
      receive autologous blood clot. CONCLUSION: Plugging of biopsy tracks with ABCS,
      particularly after biopsy of deep lung lesions, significantly reduced the
      frequency of pneumothorax-particularly of large pneumothoraces-and, therefore,
      the need for treatment and the attendant cost.

PMID- 10887233
TI  - Obliquely oriented superior accessory fissure of the lower lobe of the lung: CT
      evaluation of the normal appearance and effect on the distribution of parenchymal
      and pleural opacities.
AB  - PURPOSE: To review computed tomographic (CT) and radiographic features of an
      oblique superior accessory fissure in the lower lobe of the lung. MATERIALS AND
      METHODS: CT scans in 34 patients with a prospectively identified accessory
      fissure of the lower lobe were reviewed and correlated with chest radiographs (31
      patients). The fissure and its relationship to segmental bronchovascular
      structures were evaluated on transverse scans. Three-dimensional (3D) shaded
      surface display (SSD) reconstructions were obtained from spiral volume data (six
      patients). RESULTS: Thirty-four patients had 36 accessory fissures (26 right, 10
      left). Four of the 36 accessory fissures were manifested by a normal fissure
      line; two, by slight thickening or minimal linear atelectasis; 16, by thicker
      linear or subsegmental atelectasis; two, by contiguous tumor infiltration; one,
      by adjacent consolidation; and 11, by intrafissural extension of pleural fluid.
      Analysis of bronchovascular structures revealed that this fissure was the
      superior accessory fissure. The 3D SSD reconstructions demonstrated an oblique
      orientation. On frontal radiographs, presence of this fissure correlated with a
      curvilinear band of atelectasis coursing inferomedially and obliquely from its
      intersection with the lateral aspect of the major fissure toward the infrahilar
      region on the right and the heart border on the left. Chest radiographs also
      showed intrafissural extension of pleural fluid. CONCLUSION: A superior accessory
      fissure of the lower lobe, more common on the right than on the left, can be
      identified at transverse CT. Contrary to previous descriptions, it may be
      oblique, as findings on transverse images suggest and 3D SSD reconstructions
      confirm. Its presence correlates with characteristic patterns of atelectasis and
      pleural fluid collection on conventional radiographs.

PMID- 10887234
TI  - Normal and hypoplastic fetal lungs: volumetric assessment with prenatal single
      shot rapid acquisition with relaxation enhancement MR imaging.
AB  - PURPOSE: To determine which parameters are most closely correlated with normal
      fetal total lung volume and to investigate the use of these parameters in the
      evaluation of fetal pulmonary hypoplasia. MATERIALS AND METHODS: Single-shot
      rapid acquisition with relaxation enhancement (RARE) magnetic resonance (MR)
      imaging was used to perform planimetric measurement of total lung volume in 46
      fetuses at 18-32 weeks gestation. Total lung volume was correlated with
      gestational age, and biometric parameters in fetuses were correlated with normal
      chest findings at ultrasonography (US) (n = 24). This analysis was used to
      evaluate relative lung volume in fetuses suspected of having pulmonary hypoplasia
      (n = 22). RESULTS: Normal fetal total lung volume was strongly correlated with
      liver volume measured at MR imaging (r = 0.94), fetal weight estimated at US (r =
      0.93), head circumference measured at US (r = 0.90), and gestational age (r =
      0.87). In fetuses suspected of having pulmonary hypoplasia, the relative lung
      volume varied from 4.6% to 81.6% when the observed total lung volume was
      expressed as a percentage of the predicted total lung volume. CONCLUSION: Normal
      fetal total lung volume is strongly correlated with biometric measurements.
      Relative fetal lung volume can be calculated by expressing the observed volume as
      a percentage of the predicted volume calculated from biometric measurements;
      knowledge of the relative fetal lung volume assists in the confirmation and
      quantification of fetal pulmonary hypoplasia.

PMID- 10887235
TI  - Congenital diaphragmatic hernia in neonates: variations in umbilical catheter and
      enteric tube position.
AB  - PURPOSE: To evaluate anatomic variations of support apparatus position on
      radiographs obtained in neonates with congenital diaphragmatic hernia (CDH).
      MATERIALS AND METHODS: The authors evaluated radiographs obtained in 71 neonates
      with CDH to determine whether nasogastric tubes, umbilical venous catheters, and
      umbilical arterial catheters deviated from their expected anatomic course. The
      relationship between deviation patterns and hernia contents was evaluated.
      RESULTS: Sixty-eight neonates-54 with left-sided CDH and 14 with right-sided CDH
      had a nasogastric tube. The tubes in 21 patients with left-sided CDH had a normal
      anatomic course at radiography. Nineteen of these patients did not have stomach
      in the hernia. In 13 patients, the tip of the nasogastric tube was lodged at the
      esophagogastric junction. In 17 patients, the tube was in the left hemithorax. In
      all 30 of these patients, the stomach was within the CDH. All nasogastric tubes
      in the 14 patients with right-sided CDH had leftward deviation. Thirty-seven
      patients-27 with left-sided CDH and 10 with right-sided CDH-had umbilical venous
      catheters. The catheters in 12 patients with left-sided CDH had apex leftward
      convexity. The umbilical venous catheter in eight patients with right-sided CDH
      had rightward shift; all eight patients had liver herniation. CONCLUSION: The
      positions of nasogastric tubes and umbilical venous catheters vary in several
      predictable patterns in neonates with CDH. Knowledge of these variations may be
      helpful for supporting the diagnosis of CDH in unclear cases and thus avoiding
      unnecessary apparatus adjustments, and for predicting hernia contents.

PMID- 10887236
TI  - Pulmonary tuberculoma evaluated by means of FDG PET: findings in 10 cases.
AB  - PURPOSE: To describe findings of pulmonary tuberculoma at 2-[fluorine 18]fluoro-2
      deoxy-D-glucose (FDG) positron emission tomography (PET). MATERIALS AND METHODS:
      Ten consecutive patients who underwent PET and subsequently were proved to have
      pulmonary tuberculoma were analyzed. Tuberculosis was proved histopathologically
      in eight by means of wedge resection or lobectomy (n = 7) or needle biopsy (n =
      1) and in two by means of clinical follow-up for more than 2 years. PET scans
      were evaluated by using peak standardized uptake values. Computed tomographic
      (CT) and histopathologic findings also were reviewed. RESULTS: Nine of 10
      tuberculomas showed FDG uptake at PET, and the mean peak standardized uptake
      value was 4.2 +/- 2.2 (SD). FDG uptake (range, 1. 9-3.7) in lesions adjacent to
      main abnormalities was demonstrated in four patients. On CT scans, the mean of
      the longest nodule diameters was 21 mm +/- 8, and there were some areas of
      branching linear opacities or satellite nodules that suggested pulmonary
      tuberculosis in seven patients. Histopathologic findings were chronic
      granulomatous inflammation with caseation necrosis (n = 7) and healed
      tuberculosis with aspergilloma (n = 1). CONCLUSION: Pulmonary tuberculoma
      commonly causes an increase in FDG uptake. These results suggest that in
      geographic regions with a high prevalence of granulomatous lesions, positive FDG
      PET results should be interpreted with caution in differentiating benign from
      malignant pulmonary abnormalities.

PMID- 10887237
TI  - CT and arteriography in the evaluation of indirect myocardial revascularization
      with a free-muscle transplant: initial experience.
AB  - PURPOSE: To examine patients with advanced cardiovascular disease with radiology
      after indirect myocardial revascularization with a free-skeletal-muscle
      transplant and to determine whether the attached vessel remains patent over the
      middle and long terms. MATERIALS AND METHODS: In 10 patients with advanced,
      inoperable cardiovascular disease treated with indirect myocardial
      revascularization with a free-muscle transplant, radiologic follow-up was
      performed postoperatively and every 6 months. All 10 patients underwent selective
      arteriography of the anastomosed vessel and contrast material-enhanced helical
      computed tomography (CT) (transverse sections and reconstructions). RESULTS: All
      patients showed adequate vascular conditions postoperatively, as did nine of 10
      patients after 1 year. In one patient, the anastomosed artery was occluded. CT
      showed time-dependent muscle degeneration in all patients. Postoperative,
      contrast-enhanced, superselective CT showed an area of high-attenuating uptake in
      the muscle transplant in all patients. After 1 year, CT depicted perfusion
      defects of the skeletal muscle in two patients. In eight patients, however, small
      vascular bridges from the skeletal muscle to the myocardium were detected.
      Radiologic results correlated well with clinical outcome and stress
      electrocardiograms. CONCLUSION: Helical intraarterial CT and arteriography were
      sensitive in depicting enhancement and remaining vital function in nine of 10
      patients after indirect myocardial revascularization with a free-muscle
      transplant. This combination seems promising for postoperative examination in
      such patients.

PMID- 10887239
TI  - Case 28

PMID- 10887238
TI  - Myocardial fiber shortening in humans: initial results of MR imaging.
AB  - PURPOSE: To use diffusion-sensitive magnetic resonance (MR) imaging to obtain
      images of fiber orientation in vivo and to map fiber shortening in humans by
      means of integrating such data with strain images. MATERIALS AND METHODS: Images
      of fiber shortening for midventricular short-axis sections were acquired in eight
      healthy subjects. Fiber orientation maps obtained by means of diffusion-sensitive
      MR imaging were coregistered with systolic strain maps obtained by means of
      velocity-sensitive MR imaging. Fiber shortening was quantified by use of the
      component of systolic strain in the fiber direction. RESULTS: The results were
      reproducible among subjects and were consistent with published values. MR imaging
      of myocardial fibers showed axisymmetric progression of fiber angles from -90
      degrees epicardially to +90 degrees endocardially, with maxima near 0 degrees.
      Fiber shortening (mean, 0.12 +/- 0.01 [SD]) was more uniform than radial,
      circumferential, longitudinal, or cross-fiber strain or any principal strain.
      Fiber orientation coincided with the direction of maximum contraction
      epicardially, with that of minimum contraction endocardially, and varied between
      these extremes linearly with wall depth (r = 0.6). CONCLUSION: Registered
      diffusion and strain MR imaging can be used quantitatively to map fiber
      orientation and its relations to myocardial deformation in humans.

PMID- 10887240
TI  - Case 24: Afferent loop syndrome.

PMID- 10887241
TI  - Lymphangioleiomyomatosis: abdominopelvic CT and US findings.
AB  - PURPOSE: To describe the abdominal computed tomographic (CT) and ultrasonographic
      (US) findings in patients with thoracic lymphangioleiomyomatosis (LAM) and to
      relate the prevalence of the findings to the severity of pulmonary disease.
      MATERIALS AND METHODS: Eighty patients with LAM underwent chest and
      abdominopelvic CT and abdominopelvic US. The images were reviewed prospectively
      by one radiologist, and the abdominal findings were recorded and correlated with
      the severity of pulmonary disease at thin-section CT. RESULTS: Sixty-one (76%) of
      80 patients had positive abdominal findings. The most common abdominal findings
      included renal angiomyolipoma (AML) in 43 patients (54%), enlarged abdominal
      lymph nodes in 31 (39%), and lymphangiomyoma in 13 (16%). Less common findings
      included ascites in eight (10%), dilatation of the thoracic duct in seven (9%),
      and hepatic AML in three (4%). A significant correlation (P =.02) was observed
      between enlarged abdominal lymph nodes and increased severity of lung disease.
      CONCLUSION: There are characteristic abdominal findings in patients with LAM
      that, in conjunction with the classic thin-section CT finding of pulmonary cysts,
      are useful in establishing this diagnosis.

PMID- 10887242
TI  - Hepatocellular carcinoma in the cirrhotic liver: double-contrast MR imaging for
      diagnosis.
AB  - PURPOSE: To measure the sensitivity and accuracy of double-contrast magnetic
      resonance (MR) imaging for the diagnosis of hepatocellular carcinoma (HCC) in the
      cirrhotic liver. MATERIALS AND METHODS: Twenty-seven patients with MR features of
      dysplastic nodules and/or HCC were examined. T2-weighted spin-echo and T1
      weighted gradient-echo imaging was performed before and after superparamagnetic
      iron oxide (SPIO) administration and immediately followed by T1-weighted gradient
      echo imaging at 10, 40, and 120 seconds after bolus injection of a gadolinium
      based contrast material. Nonenhanced, nonenhanced plus SPIO-enhanced, and
      nonenhanced plus SPIO-enhanced plus gadolinium-enhanced images were reviewed.
      Alternative-free response receiver operating characteristic (ROC) methodology was
      used to analyze the results, which were correlated with histopathologic findings
      after transplantation in 15 patients and at biopsy in 12. Lesions visualized with
      all three techniques were characterized as a dysplastic nodule or HCC, and ROC
      analysis was performed. RESULTS: For all observers, SPIO-enhanced MR imaging
      (mean accuracy, 0.76) was more accurate than nonenhanced MR imaging (mean
      accuracy, 0.64) (P <.04), and double-contrast MR imaging (mean accuracy, 0.86)
      was more accurate than SPIO-enhanced imaging (P <.05). Both types of lesions were
      correctly characterized with all three techniques, although observer confidence
      for lesion characterization was greatest with double-contrast MR imaging.
      CONCLUSION: Double-contrast MR imaging significantly improves the diagnosis of
      HCC compared with SPIO-enhanced and nonenhanced imaging (P <.01).

PMID- 10887243
TI  - Islet cell tumor of the pancreas: biphasic CT versus MR imaging in tumor
      detection.
AB  - PURPOSE: To compare the effectiveness of biphasic computed tomography (CT) and
      magnetic resonance (MR) imaging in the detection of pancreatic islet cell tumors.
      MATERIALS AND METHODS: Retrospective quantitative, qualitative, and receiver
      operating characteristic analyses of biphasic CT and MR imaging were performed in
      19 patients with 26 histopathologically proved islet cell tumors. Delayed
      arterial dominant-phase (AP) and portal venous-phase (PVP) biphasic CT was
      performed after the administration of contrast material. MR imaging included T1
      weighted spin-echo (SE) and T2-weighted SE or fast SE imaging, fat-saturated T1
      weighted SE imaging, dynamic contrast material-enhanced T1-weighted gradient-echo
      imaging, and delayed enhanced T1-weighted SE imaging with or without fat
      saturation. RESULTS: PVP CT and delayed enhanced T1-weighted MR imaging had the
      highest A(z) values (0.98 and 0.97, respectively; P <.05). Delayed enhanced T1
      weighted MR imaging had the highest relative sensitivity (14-15 [74%-79%] of 19
      lesions), followed by PVP CT (18-19 [69%-73%] of 26 lesions), AP CT (17-19 [65%
      73%] of 26 lesions), fat-saturated T1-weighted MR imaging (eight to 10 [57%-71%]
      of 14 lesions), T2-weighted (16-17 [62%-65%] of 26 lesions), T1-weighted (15-18
      [58%-69%] of 26 lesions) MR imaging, and dynamic MR imaging (nine [56%] of 16
      lesions). CONCLUSION: Biphasic (especially PVP) CT and MR imaging have similar
      effectiveness in the detection of islet cell tumors if fat-saturated T1-weighted
      and delayed enhanced T1-weighted MR imaging are included.

PMID- 10887244
TI  - Diagnosis of acute appendicitis: comparison of 5- and 10-mm CT sections in the
      same patient.
AB  - PURPOSE: To compare 5- and 10-mm computed tomographic (CT) sections in the same
      patient to diagnose acute appendicitis. MATERIALS AND METHODS: During an 11-month
      period, 100 consecutive patients clinically suspected to have acute appendicitis
      underwent abdominal and pelvic CT. Helical, 10-mm-collimated sections from the
      diaphragm to the pubic symphysis and 5-mm-collimated sections through the lower
      part of the abdomen and upper part of the pelvis were obtained. The 10- and 5-mm
      sections from each patient were separated into two groups and were interpreted
      independently by two abdominal imaging attending physicians who were blinded to
      the final results. The interpretations were correlated with the histopathologic
      or final clinical diagnoses. RESULTS: Data analysis from blinded reader
      interpretations of the 5- and 10-mm sections, respectively, revealed
      sensitivities of 99% and 82% (P <.001), specificities of 98% and 95% (P =.426),
      and accuracies of 99% and 89% (P <.001). Among the 48 cases of acute
      appendicitis, abnormal appendices were identified in 94% (n = 45) and 69% (n =
      33) (P <.05) on 5- and 10-mm-collimated sections, respectively. Right-lower
      quadrant inflammatory changes were identified in 98% (n = 47) and 71% (n = 34) (P
      <.05) on 5- and 10-mm-collimated sections, respectively. Normal appendices were
      identified in 75% (n = 39) and 52% (n = 27) of the 52 negative cases on 5- and 10
      mm sections (P =.025), respectively. CONCLUSION: Use of thin-section CT
      significantly improves the diagnosis of acute appendicitis.

PMID- 10887245
TI  - The coffee bean sign.

PMID- 10887246
TI  - Patient and personnel exposure during CT fluoroscopy-guided interventional
      procedures.
AB  - PURPOSE: To estimate patient dose and personnel exposure from phantom
      measurements during computed tomographic (CT) fluoroscopy, to use the estimates
      to provide users with dose information, and to recommend methods to reduce
      exposure. MATERIALS AND METHODS: Surface dose was estimated on a CT dosimetric
      phantom by using thermoluminescent dosimetric (TLD) and CT pencil chamber
      measurements. Scatter exposure was estimated from scattered radiation measured at
      distances of 10 cm to 1 m from the phantom. Scatter exposures measured with and
      without placement of a lead drape on the phantom surface adjacent to the scanning
      plane were compared. RESULTS: Phantom surface dose rates ranged from 2.3 to 10. 4
      mGy/sec. Scattered exposure rates for a commonly used CT fluoroscopic technique
      (120 kVp, 50 mA, 10-mm section thickness) were 27 and 1.2 microGy/sec at 10 cm
      and 1 m, respectively, from the phantom. Lead drapes reduced the scattered
      exposure by approximately 71% and 14% at distances of 10 and 60 cm from the
      scanning plane, respectively. CONCLUSION: High exposures to patients and
      personnel may occur during CT fluoroscopy-guided interventions. Radiation
      exposure to patients and personnel may be reduced by modifying CT scanning
      techniques and by limiting fluoroscopic time. In addition, scatter exposure to
      personnel may be substantially reduced by placing a lead drape adjacent to the
      scanning plane.

PMID- 10887247
TI  - Stair-step artifacts with single versus multiple detector-row helical CT.
AB  - PURPOSE: To compare the effects of acquisition parameters on the magnitude and
      appearance of artifacts between single and multiple detector-row helical computed
      tomography (CT). MATERIALS AND METHODS: A cylindric (12.7 x 305.0-mm) acrylic rod
      inclined 45 degrees relative to the z axis was scanned at the isocenter and 100
      mm from the isocenter with single detector-row (single-channel) helical CT (beam
      width, 1-10 mm; pitch, 1.0, 2.0, or 3.0) and multiple detector-row (four-channel)
      helical CT (detector width, 1. 25, 2.5, 3.75, and 5 mm; pitch, 0.75 or 1.5). The
      SD of radius measurements along the rod (SD(r)) was used to quantify artifacts in
      all 72 data sets and to analyze their frequency patterns. Volume-rendered images
      of the data sets were ranked by six independent and blinded readers; findings
      were correlated with acquisition parameters and SD(r) measurements. RESULTS:
      SD(r) was smaller in four- than in single-channel helical CT for any given table
      increment (TI). In single-channel helical CT, SD(r) increased linearly with beam
      width and geometrically with pitch. In four-channel helical CT, SD(r)
      measurements were directly proportional to the TI, regardless of the detector
      width and pitch combination used. Off-center object position on average increased
      SD(r) by a factor of 1.6 for single-channel helical CT and by a factor of 2.0 for
      four-channel helical CT. Subjective rankings of image quality correlated
      excellently with SD(r) (Spearman r = 0.94, P <.001). CONCLUSION: Artifacts are
      quantitatively and subjectively smaller with four- compared with single-channel
      helical CT for any given TI.

PMID- 10887248
TI  - Sarcoma after radiation therapy: retrospective multiinstitutional study of 80
      histologically confirmed cases. Radiation Therapist and Pathologist Groups of the
      Federation Nationale des Centres de Lutte Contre le Cancer.
AB  - PURPOSE: To evaluate the best strategy for treatment of sarcoma that occurs after
      radiation therapy. MATERIALS AND METHODS: Records were retrospectively reviewed
      for 80 patients with a confirmed histologic diagnosis of sarcoma that occurred
      after radiation therapy performed during 1975-1995. The patients were treated for
      breast cancer (n = 33, 42%), non-Hodgkin lymphoma (n = 9, 11%), cervical cancer
      (n = 9, 11%), benign lesions (n = 4, 5%), or other tumors (n = 25, 31%). Sarcoma
      occurred after a mean latency of 12 years (range, 3-64 years), with most (70%)
      developing in the soft tissue. Treatment included surgery (28 patients), surgery
      and chemotherapy (18 patients), chemotherapy only (15 patients), and radiation
      therapy (14 patients). RESULTS: By the end of the study, 51 patients were dead,
      including 46 due to sarcoma. Median survival was 23 months. Overall survival
      rates at 2 and 5 years, respectively, were 69% and 39% for patients treated with
      surgery, 10% and 0% for those treated with chemotherapy, and 52% and 35% for
      those treated with surgery and chemotherapy (P =.001). The 2- and 5-year rates
      for survival without recurrence were 54% and 32%, respectively. CONCLUSION: The
      results confirm the beneficial effect of surgery. Further study is needed to
      explore the roles of combined treatments.

PMID- 10887249
TI  - Natural progression of osteochondritis dissecans of the humeral capitellum:
      initial observations.
AB  - PURPOSE: To determine the earliest findings, subsequent changes, and natural
      course of osteochondritis dissecans of the humeral capitellum. MATERIALS AND
      METHODS: Among 95 patients with osteochondritis dissecans of the humeral
      capitellum, 16 (mean age, 12.5 years) were selected for this retrospective study
      because they seemed to have early osteochondritis dissecans and had been followed
      up without any surgical treatment for 6 months or more (mean, 3.5 years).
      RESULTS: The initial imaging appearances of the 16 patients' lesions were divided
      into two types: localized subchondral bone flattening without fragments in seven,
      and nondisplaced fragments in nine. Patients with lesion flattening had younger
      ages and significantly shorter durations of symptoms, and most had open growth
      plates. In five of the seven with flattening, new bone formed over the flattened
      bone, and the fragments united after arm motion reduction. In contrast, patients
      with nondisplaced fragments at clinical presentation had longer durations of
      symptoms with continued arm motion, and their nondisplaced fragments failed to
      unite. CONCLUSION: The earliest feature of osteochondritis dissecans is
      subchondral bone flattening, over which new bone subsequently forms. The new bone
      then can unite with the underlying bone. However, if subjected to repetitive
      forces over a given time, unstable fragments develop. These fragments, even if
      not yet displaced, are unable to unite.

PMID- 10887250
TI  - Calcium pyrophosphate dihydrate crystal deposition in and around the atlantoaxial
      joint: association with type 2 odontoid fractures in nine patients.
AB  - PURPOSE: To investigate the histopathologic anatomy of calcium pyrophosphate
      dihydrate (CPPD) crystal deposition in and around the atlantoaxial joint and the
      association between CPPD crystal deposition and subchondral cysts, erosions, and
      fracture involving the odontoid process of the axis. MATERIALS AND METHODS: One
      adult cadaver demonstrating calcification in the retro-odontoid area at computed
      tomography (CT) was selected for further radiography, CT, and magnetic resonance
      (MR) imaging at the C1-2 level. Anatomic sectioning and histologic evaluations
      were performed in the specimen. For clinical study, radiographs (n = 5), CT scans
      (n = 8), and MR images (n = 6) in nine patients (mean age, 74.4 years) with
      odontoid process fractures and CPPD crystal deposits in and around the
      atlantoaxial joint were reviewed. RESULTS: In the cadaveric specimen, radiography
      and CT demonstrated calcifications in the transverse ligament; histologic
      evaluation confirmed that these calcifications were CPPD crystal deposits. In all
      nine patients, radiography (n = 5) and CT (n = 8) also showed calcification in
      areas adjacent to the odontoid process, which included the transverse ligament.
      T1- and T2-weighted MR imaging showed a retro-odontoid mass of low signal
      intensity that compressed the cervical cord in six patients. CT, MR imaging, or
      both demonstrated subchondral cysts, osseous erosions, or a type 2 odontoid
      fracture in all patients. CONCLUSION: CPPD crystal deposition disease involving
      the C1-C2 articulation can be a clinically important entity that may place
      affected patients at increased risk of pathologic fracture of the odontoid
      process.

PMID- 10887251
TI  - Selenium-based digital radiography in the detection of bone lesions: preliminary
      experience with experimentally created defects.
AB  - PURPOSE: To compare the diagnostic performance of selenium-based digital
      radiography with that of conventional screen-film radiography and storage
      phosphor radiography for the detection of bone lesions simulating osteolyses.
      MATERIALS AND METHODS: Artificial osseous lesions 1.0-3.0 mm in diameter were
      created in 80 of 160 predefined regions in 16 porcine femoral specimens.
      Specimens were enclosed in containers filled with paraffin to ensure accurate
      repositioning and to obtain an absorption condition comparable to that of a human
      extremity. Imaging was performed with a selenium-based digital radiography
      system, a conventional screen-film system, and a storage phosphor radiography
      system with an exposure identical to that used during clinical imaging. The
      presence of a lesion was assessed with a five-point confidence scale. Receiver
      operating characteristic (ROC) analysis was performed for a total of 1,440
      observations (480 per modality), and diagnostic performance was estimated with
      the area under the ROC curve (A(z)). Differences in diagnostic performance were
      assessed with the paired Student t test. RESULTS: ROC analysis results showed
      A(z) values of 0.656 for selenium-based digital radiography, 0.679 for storage
      phosphor radiography, and 0.680 for conventional screen-film radiography.
      Differences between the three modalities were not significant (P =.60-.93).
      CONCLUSION: Image quality with selenium-based digital radiography was comparable
      to that with conventional screen-film radiography and storage phosphor
      radiography.

PMID- 10887252
TI  - MR imaging of nitrosyl-iron complexes: experimental study in rats.
AB  - PURPOSE: To assess the influence of several nitrosyl-iron complexes on proton
      nuclear spin relaxation rates to establish a magnetic resonance (MR) imaging
      technique for nitric oxide. MATERIALS AND METHODS: The influence of aqueous
      phantom solutions of nitrosyl-iron complexes on proton relaxation rates was
      analyzed for signal enhancement at conventional 1.5-T MR imaging. To induce
      formation of nitrosyl-iron complexes in a biologic tissue, isolated rat liver was
      perfused with a saline solution of the NO donor sodium nitroprusside (SNP), and
      the MR signal intensity was examined thereafter. RESULTS: All investigated
      nitrosyl-iron complexes shortened the longitudinal, or T1, and transverse, or T2,
      relaxation times in a concentration-dependent fashion. Relaxivities were highest
      with a dinitrosyl-iron complex bound to albumin and with a water-soluble
      mononitrosyl-iron dithiocarbamate complex. The contrast properties of 240
      micromol/L of a paramagnetic nitrosyl-iron complex were sufficient to
      substantially enhance the signal intensity of SNP-perfused rat livers at hydrogen
      1 MR imaging. CONCLUSION: Nitrosyl-iron complexes exhibit a contrast effect at MR
      imaging that can be exploited for NO imaging in living animals and patients with
      conventional (1)H MR imaging techniques.

PMID- 10887253
TI  - Effect of gadolinium concentration on renal signal intensity: An in vitro study
      with a saline bag model.
AB  - PURPOSE: To compare the effects of gadolinium concentration on intermediate
      weighted fast inversion-recovery and T2-weighted fast spin-echo magnetic
      resonance (MR) images by using a saline bag model of the kidney. MATERIALS AND
      METHODS: Normal-saline bags containing gadopentetate dimeglumine in
      concentrations of 0-20 mmol/L were imaged by using a variety of pulse sequences.
      Signal intensity was measured. RESULTS: Signal intensity loss at high gadolinium
      concentrations (negative enhancement) was demonstrated with all MR sequences.
      Increasing T2 weighting increased the negative enhancement effect and reduced the
      minimum gadolinium concentration at which negative enhancement was seen. The
      results of this study match theoretic predictions. CONCLUSION: The negative
      enhancement of normal renal tissue seen in intermediate-weighted fast inversion
      recovery MR imaging is caused by T2 shortening at high gadolinium concentrations.
      Thus, gadolinium-enhanced T2-weighted fast spin-echo imaging also is expected to
      show negative enhancement and may prove to be a superior sequence for MR imaging
      of pyelonephritis. Further clinical investigation is warranted.

PMID- 10887254
TI  - Spinal dysraphism at MR urography: initial experience.
AB  - PURPOSE: To prospectively evaluate the role of magnetic resonance (MR) urography
      in the radiologic assessment of patients with spinal dysraphism. MATERIALS AND
      METHODS: Fourteen patients with spinal dysraphism were referred for MR urography
      with half-Fourier rapid acquisition with relaxation enhancement (RARE)
      (repetition time msec/echo time msec = 11.9/95) and RARE (2,800/1,100) sequences
      on a 1.5-T MR machine. Six patients did not tolerate MR urography owing to
      claustrophobia (n = 4) or flexion deformities (n = 2), giving a final success
      rate of 57% (eight patients). Two patients had a single kidney (one after
      nephrectomy, one with a crossed-fused ectopic kidney). Images were jointly
      assessed by two radiologists and compared with excretory urographic studies. The
      signal intensity ratio and contrast-to-noise ratio were also calculated. RESULTS:
      Visualization of the kidneys, pelvicaliceal system, and ureters was better with
      half-Fourier RARE than with RARE imaging, whereas visualization of the bladder
      was comparable with both sequences. The mean signal intensity ratios for half
      Fourier RARE and RARE sequences, respectively, were 16.2 +/- 3.65 and 19.2 +/-
      3.65 (P =. 58, factorial analysis of variance model), whereas the mean contrast
      to-noise ratios were 55.4 +/- 5.16 and 47.8 +/- 5.16 (P =. 34). Cortical scarring
      was depicted more clearly at MR urography than at excretory urography, whereas a
      renal calculus seen at excretory urography was not detected at MR urography.
      CONCLUSION: MR urography was feasible in 57% of patients with spinal dysraphism
      and is a safe, accurate method of evaluating the upper urinary tract.

PMID- 10887255
TI  - Adnexal masses in women with breast cancer: US findings with clinical and
      histopathologic correlation.
AB  - PURPOSE: To correlate ultrasonographic (US), clinical, and histopathologic
      findings in patients with breast cancer who underwent surgery for adnexal masses
      evident at US. MATERIALS AND METHODS: A database search yielded 54 patients with
      breast cancer and with adnexal masses at US and histopathologic examinations.
      Clinical, US, and histopathologic findings were correlated. RESULTS: Forty (74%)
      patients had benign adnexal masses, and 14 (26%) had malignant masses; three
      patients had both benign and malignant ovarian masses. Seven patients had primary
      ovarian cancer, and seven had breast metastases to the ovary. All breast
      metastases to the ovary were bilateral solid masses at histopathologic
      examination and occurred in women with stage IV breast carcinoma at the time of
      US. Eleven ovaries with breast metastases were solid at US. The remaining three
      ovaries with breast metastases had cystic components at US because of hemorrhage
      or coexistent benign ovarian cysts. Four of seven patients with primary ovarian
      carcinoma had bilateral ovarian tumors, and seven of 11 ovarian carcinomas were
      predominantly cystic at US. No patient with primary ovarian carcinoma had stage
      IV breast cancer. CONCLUSION: In this small series, half the ovarian malignancies
      in patients with breast cancer were primary ovarian carcinomas and half were
      breast metastases to the ovary. Breast metastases to the ovary most frequently
      are bilateral solid masses at US and are associated with stage IV disease at the
      time of US.

PMID- 10887256
TI  - MR imaging in patients with nipple discharge: initial experience.
AB  - PURPOSE: To investigate the potential of magnetic resonance (MR) imaging in
      patients with nipple discharge. MATERIALS AND METHODS: Between February 1992 and
      December 1998, 23 patients with nipple discharge underwent contrast material
      enhanced MR imaging at 1.5 T. Mammographic findings were negative in 22 of 23
      patients and revealed asymmetry in one patient. Galactography was attempted in
      two patients, with negative findings in one patient and no success in the other.
      Fifteen of 23 patients underwent excisional biopsy-seven of 15 with MR imaging
      guided localization, and one of 15 with mammographic localization. Eight of 23
      patients were followed up clinically (range, 7-24 months; mean, 20 months).
      RESULTS: In 11 of the 15 (73%) patients who underwent excisional biopsy, MR
      imaging findings correlated with histopathologic findings. MR imaging
      demonstrated four of six benign papillomas and one of two fibroadenomas as
      circumscribed, enhancing subareolar masses. Findings of one MR imaging
      examination were negative, and benign tissue was found at excisional biopsy. MR
      imaging findings were suspicious in six of the seven patients with excisional
      biopsy findings of malignancy (regional enhancement [n = 2], ductal enhancement
      [n = 2], peripherally enhancing mass [n = 1], and spiculated mass [n = 1]). In
      one of the seven patients, a benign-appearing intraductal mass was identified at
      MR imaging; excisional biopsy revealed a benign papilloma with an adjacent focus
      of DCIS. CONCLUSION: MR imaging can help identify both benign and malignant
      causes of nipple discharge. It potentially offers a noninvasive alternative to
      galactography.

PMID- 10887257
TI  - Focal fibrosis of the breast: imaging characteristics and histopathologic
      correlation.
AB  - PURPOSE: To characterize mammographic and ultrasonographic (US) features of focal
      fibrosis of the breast (FFB), to compare the radiologic and histopathologic
      findings, to investigate the incidence of FFB, and to determine if
      histopathologic diagnosis of FFB is an acceptable diagnosis for specific
      mammographic and US findings. MATERIALS AND METHODS: Retrospective review of
      findings from 1,268 surgical excisional and 796 percutaneous breast biopsies (290
      US-guided, 370 stereotactically guided, and 136 vacuum-assisted stereotactically
      guided) revealed 44 (2.1%) diagnoses of FFB. Mammographic and US features were
      correlated with histopathologic types. RESULTS: Thirty-seven (84%) of the 44
      lesions diagnosed as FFB were visualized on mammograms and appeared as six (14%)
      circumscribed masses, two (5%) lobulated masses, one (2%) microlobulated mass, 11
      (25%) obscured masses, two (5%) architectural distortions, and 15 (34%)
      asymmetric densities. Seven palpable lesions were not visualized on mammograms.
      Thirty-three of the 44 lesions were evaluated at US; 25 (76%) of 33 were visible.
      Twenty (80%) of 25 were well-defined hypoechoic masses; three (12%), ill-defined
      masses; and two (8%), marked shadowing without visible mass. At histopathologic
      examination, 17 (39%) of the 44 lesions were characterized as mass-like fibrosis;
      14 (32%), as nodular fibrosis; 12 (27%), as haphazard fibrosis; and one (2%), as
      septal fibrosis. Histopathologic type and specific imaging findings did not
      correlate statistically. CONCLUSION: FFB is a histopathologic entity that has a
      wide spectrum of imaging findings. It is an acceptable histopathologic result of
      percutaneous breast biopsy, provided that careful radiologic-histopathologic
      clinical correlation is performed.

PMID- 10887258
TI  - US evaluation of the uterus in patients with postmenopausal bleeding: A positive
      effect on diagnostic decision making.
AB  - PURPOSE: To assess the accuracy of hysterosonography (HSG) and its role in
      diagnostic confidence and therapeutic clinical decision making among referring
      physicians caring for patients with postmenopausal bleeding (PMB). MATERIALS AND
      METHODS: One hundred twenty-three patients with PMB underwent transvaginal
      ultrasonography (US) and HSG. They were examined for cancer, polyp, leiomyoma,
      and hyperplasia. Physicians assessed the effect of the studies on diagnostic
      confidence and care, including biopsy, dilation and curettage, hysteroscopy,
      hormone manipulation, and/or patient reassurance. Abnormality was proved with
      histopathologic evaluation, and normality, with 6-month follow-up. RESULTS: In 10
      patients, HSG was unsuccessful, and in 15, follow-up was incomplete; this left 98
      patients. Endometrial polyps were seen in 46 (47%) patients; leiomyoma, in 11
      (11%); cancer, in four (4%); hyperplasia, in eight (8%); and normal findings, in
      29 (30%). Our calculations yielded a sensitivity of 98% and a specificity of 88%.
      In 86 (88%) patients, US added certainty to the diagnosis; in 78 (80%), it
      resulted in a change in patient treatment. CONCLUSION: HSG and transvaginal US in
      patients with PMB improves diagnostic accuracy, clinical decision making, and the
      clinician's diagnostic certainty. In patients with benign causes of PMB, the
      absence of abnormality at HSG and a normal endometrial biopsy result may
      eliminate the need for further studies.

PMID- 10887259
TI  - Role of emergency medicine physicians in US performed in patients in the
      emergency department: how substantial is their participation?
AB  - PURPOSE: To determine the extent to which emergency medicine physicians have
      assumed responsibility for performing and interpreting ultrasonographic (US)
      studies in emergency departments (EDs) in the United States. MATERIALS AND
      METHODS: The national 1997 Medicare Part B database was searched by using
      standard US procedure codes, location codes, and physician specialty codes. The
      authors determined how many US studies were performed in EDs and what percentage
      of those studies were performed by emergency medicine physicians, radiologists,
      or other physicians. RESULTS: During 1997, 234,820 ED US studies within nine
      major examination categories were performed in Medicare patients nationwide.
      Emergency medicine physicians performed 1,551 (0.7%) of these studies. When
      echocardiographic examinations were excluded, emergency medicine physicians
      performed 458 (0.2%) of the remaining total of 196,158 studies. CONCLUSION:
      Although emergency medicine physicians have claimed to be actively involved in ED
      US on a broad scale, the data reveal that their involvement in 1997 was minimal.
      This raises doubt as to whether they can properly train their residents to
      perform US or maintain their own competence at acceptable levels.

PMID- 10887260
TI  - Technical cost of radiologic examinations: analysis across imaging modalities.
AB  - PURPOSE: To determine the individual technical costs of general diagnostic
      radiographic, ultrasonographic (US), computed tomographic (CT), magnetic
      resonance (MR) imaging, and scintigraphic examinations and interventional
      radiology. MATERIALS AND METHODS: The Radiology Cost and Productivity
      Benchmarking Study method of the University HealthSystem Consortium, a
      cooperative group of academic medical centers, was modified and extended to the
      six imaging modalities in a tertiary care academic setting. Hospital billing and
      cost records were analyzed for fiscal year 1996. Costs were divided into labor
      and nonlabor categories and were allocated to individual imaging modalities on
      the basis of resources consumed. Physician cost and hospital overhead were not
      included. Unit costs were analyzed per technical relative value unit (RVU) and
      per examination. RESULTS: The costs per technical RVU for diagnostic radiography,
      US, CT, MR imaging, scintigraphy, and interventional radiology were $65. 06,
      $28.74, $20.95, $17.69, $42.19, and $89.03, respectively. The technical costs per
      examination for diagnostic radiography, US, CT, MR imaging, scintigraphy, and
      interventional radiology were $41.92, $50.28, $112.32, $266.96, $196.88, and
      $692.60, respectively. CONCLUSION: The method of unit cost analysis for
      individual imaging modalities was successfully tested in a tertiary care setting.
      The method should be adopted to allow cost comparison across many institutions,
      which will permit the promotion of best practices.

PMID- 10887261
TI  - B-mode enhancement at phase-inversion US with air-based microbubble contrast
      agent: initial experience in humans.
AB  - Pulse- or phase-inversion ultrasonography (US) sums the signals returned from two
      180 degrees ultrasound pulses. Linear scattering from tissue results in a signal
      void while nonlinear signals from microbubbles stand out. The technique was
      applied with a US contrast agent in 39 human subjects. B-mode enhancement of
      vessels and organ parenchyma was seen in all cases. Enhancement occurred from
      flowing and stationary microbubbles. The flow-independent enhancement of normal
      and abnormal tissue represents a major advance in contrast material-enhanced US
      with many potential applications especially in tumor imaging.

PMID- 10887262
TI  - Breast cancer in vivo: contrast enhancement with thermoacoustic CT at 434 MHz
      feasibility study.
AB  - The authors performed thermoacoustic computed tomography (CT) with 434-MHz radio
      waves in five patients with documented breast cancer. Three of the patients
      underwent imaging before chemotherapy was initiated and two at the conclusion of
      their primary chemotherapy. In the former three patients, thermoacoustic CT
      demonstrated contrast enhancement in the region of the tumor. In the latter two
      patients, no contrast enhancement was seen, and pathologic examination after
      surgical resection of the area of original tumor confirmed complete remission of
      disease.

PMID- 10887263
TI  - Automated polyp detector for CT colonography: feasibility study.
AB  - An abdominal computed tomographic scan was modified by inserting 10 simulated
      colonic polyps with use of methods that closely mimic the attenuation, noise, and
      polyp-colon wall interface of naturally occurring polyps. A shape-based polyp
      detector successfully located six of the 10 polyps. When settings that enhanced
      the edge profile of polyps were chosen, eight of 10 polyps were detected. There
      were no false-positive detections. Shape analysis is technically feasible and is
      a promising approach to automated polyp detection.

PMID- 10887264
TI  - Mesial temporal sclerosis and temporal lobe epilepsy: MR imaging deformation
      based segmentation of the hippocampus in five patients.
AB  - In five patients with mesial temporal sclerosis, the authors verified the
      precision and reproducibility of hippocampal segmentations with deformation-based
      magnetic resonance (MR) imaging. The overall percentage overlap between automated
      segmentations was 92.8% (SD, 3.5%), between manual segmentations was 73.1% (SD,
      9.5%), and between automated and manual segmentations was 74.8% (SD, 10.3%).
      Deformation-based hippocampal segmentations provided a precise method of
      hippocampal volume measurement in this patient population.

PMID- 10887266
TI  - Percutaneous ablative therapies for small hepatocellular carcinoma: radio
      frequency or percutaneous ethanol injection?

PMID- 10887265
TI  - Partial fat-saturated contrast-enhanced three-dimensional MR angiography compared
      with non-fat-saturated and conventional fat-saturated MR angiography.
AB  - Abdominal three-dimensional magnetic resonance angiography was performed in 35
      patients in the equilibrium phase without fat saturation, with conventional fat
      saturation, and with fast partial fat saturation. Qualitative and quantitative
      evaluation demonstrated significantly better vessel visualization with both fat
      saturated techniques. The partial fat-saturated technique provided water-specific
      images within a breath hold, reducing motion artifacts significantly.

PMID- 10887267
TI  - Another cause for dense metaphyses.

PMID- 10887268
TI  - Abstracts of current literature

PMID- 10887269
TI  - Prevention of sudden death from ventricular arrhythmia. Canadian Cardiovascular
      Society 1999 consensus conference.

PMID- 10887270
TI  - Prevention of sudden death from ventricular arrhythmia. Epidemiology.

PMID- 10887271
TI  - The appropriate evaluation of the patient at risk for sudden death from
      ventricular arrhythmias.

PMID- 10887272
TI  - The management of acute ventricular tachycardia or fibrillation.

PMID- 10887273
TI  - Long term management of the survivor of ventricular fibrillation or sustained
      ventricular tachycardia.

PMID- 10887274
TI  - Treatment approaches for patients with sustained VT/VF.

PMID- 10887275
TI  - The role of prophylactic implantable cardioverter defibrillators to prevent
      sudden cardiac death.

PMID- 10887276
TI  - Antiarrhythmic therapy for the prevention of sudden cardiac death.

PMID- 10887277
TI  - Unusual causes of sudden cardiac death due to ventricular tachyarrhythmias.

PMID- 10887278
TI  - Quality of life issues in the management of patients with ventricular
      arrhythmias.

PMID- 10887279
TI  - Chapter 10. Current evidence on the cost effectiveness of the implantable
      cardioverter defibrillator.

PMID- 10887280
TI  - Role of cAMP-dependent signal transduction in the control of T lymphocyte
      activation.
AB  - The role of cAMP in the regulation of antigen-dependent differentiation of T
      cells is discussed with consideration of the molecular mechanisms of cAMP
      effects. Characteristics of activation signal in various T lymphocyte
      subpopulations determining differential sensitivity to cAMP are reviewed.
      Specific attention is given to the involvement of the cAMP-dependent messenger
      system in the formation of the spectrum of secreted cytokines because their level
      and ratio determine the type of immune response.

PMID- 10887281
TI  - Probing contacts of phosphate groups of oligonucleotides from the non-template
      strand of lac UV5 promoter with E. coli RNA polymerase using regioselective cross
      linking.
AB  - Contacts of phosphate groups at positions -12, -15, and -18 in relation to the
      transcription initiation site in the non-template strand of lac UV5 promoter with
      lysines or histidines of E. coli RNA polymerase in the open complex model were
      studied. A number of synthetic oligonucleotides from the -10-area of the non
      template strand containing activated 5'-terminal phosphate group were cross
      linked with holo- or core-enzyme of RNA polymerase. 5'-N-Hydroxybenzotriazole
      phosphodiesters of oligonucleotides were used as phosphate activated derivatives.
      They are capable of phosphorylating amino groups of lysines and histidines in the
      enzyme molecule that are brought into proximity with activated phosphate in the
      complex, resulting in the formation of a covalent bond between the
      oligonucleotide and the protein. The analysis of the products of cross-linking
      allowed the protein subunit and the amino acid residue taking part in the
      formation of the covalent bond for each oligonucleotide to be identified. It was
      found that all oligonucleotides from the non-template strand of promoter in the
      complex with the holo-enzyme are bound with the sigma70-subunit. When analyzing
      the products of partial cleavage of the complexes cross-linked at cysteines and
      methionines using SDS-PAGE, it was shown that phosphate at position -12 made
      contacts with His180 or His242 of the sigma70-subunit, the reactive amino acid
      residue being located between the first and second conservative regions.
      Phosphate at position -15 is located near lysines from two different areas-
      between Met413 and Met456 (regions 2.3 and 2.4) and between Met470 and Met507
      (region 3.1). Phosphate at position -18 makes preferential contacts with a lysine
      situated between Met470 and Met507 (region 3.1). Based on the analysis of
      contacts of phosphate groups and the structure of the isolated sigma70-subunit
      established previously, a scheme of the mutual arrangement of the oligonucleotide
      and the sigma70-subunit possessed by the holo-enzyme has been proposed.

PMID- 10887282
TI  - Isolation and characterization of the N-domain of bovine angiotensin-converting
      enzyme.
AB  - A method for preparation of a catalytically active fragment of bovine lung
      angiotensin-converting enzyme (ACE) has been developed. It includes limited
      proteolysis of the full-length somatic form of the enzyme by trypsin. The
      resulting fragment corresponds to the N-terminal domain of angiotensin-converting
      enzyme. The influence of chloride and sulfate anions on the enzymatic activity of
      this fragment has been investigated, and kinetic parameters for hydrolysis of
      synthetic tripeptide substrates catalyzed by the N-domain of ACE have been
      determined. Comparison of these parameters with those obtained for full-length
      somatic bovine ACE suggests that in the bovine somatic ACE molecule active
      centers located in various domains may function interdependently.

PMID- 10887283
TI  - Participation of Poly(ADP-ribose)-polymerase of nuclear matrix in DNA repair.
AB  - The poly(ADP-ribose)-polymerase activity of brain and liver cell nuclei is
      changed during X-irradiation of rats. In the nuclear matrix, poly(ADP-ribose)
      polymerase activity increases at a low dose of irradiation (1.7 Gy) and decreases
      at a high dose (6.7 Gy). A significant part of the activity of nuclear NMN
      adenylyltransferase, a key enzyme for biosynthesis of NAD (the substrate of
      poly(ADP-ribose)-polymerase), has been found in the nuclear matrix. An
      interrelation between ADP-ribosylation taking place on the matrix level and
      eukaryotic cell DNA repair is suggested.

PMID- 10887284
TI  - Effects of Ca2+-ATPase inhibitors, ionomycin, and pharmacological modulators of
      ryanodine receptor on calcium release from intracellular pools and on oscillatory
      contractile behavior in Physarum polycephalum.
AB  - Changes in calcium levels in organelles of the plasmodium of the myxomycete
      Physarum polycephalum were analyzed using the fluorescent calcium indicator
      chlortetracycline (CTC). Both the Ca2+-ATPase inhibitor 2,5;-di(tert-butyl)-1,4
      benzohydroquinone (BHQ) (100 microM) and the calcium ionophore ionomycin (1
      microM) induce a significant decrease in fluorescence level (by 30%) in CTC
      stained microplasmodia; this is caused by release of calcium from intracellular
      storage compartments. An activator of ryanodine receptors, caffeine (10-50 mM),
      is less effective on Ca2+ release than BHQ or ionomycin, and their inhibitor,
      ryanodine (100 microM), almost completely blocks the response to caffeine, but
      only slightly decreases the effects of BHQ or ionomycin. Procaine, another
      inhibitor of ryanodine receptors, at 10 mM concentration completely abolishes
      both the BHQ and the ionomycin responses, but 50 mM is necessary to block the
      effect of 25 mM caffeine. These results suggest that both the BHQ- and the
      ionomycin-dependent Ca2+ releases occur through the ryanodine receptor and are to
      be considered as calcium-induced Ca2+ release (CICR). Both the ionomycin and the
      BHQ responses persist in the presence of Cd2+, which blocks Ca2+ channels of the
      plasmalemma. In most cases, Cd2+ itself induces release of Ca2+ from the CTC
      stained calcium pool; the more effective Cd2+ is, the less the following
      ionomycin or BHQ responses occur. This indicates that Ca2+ entry through
      plasmalemma plays no significant role in the ionomycin- or BHQ-evoked initiation
      of CICR, and that the Cd2+- and BHQ/ionomycin-depleted Ca2+ stores overlap.

PMID- 10887285
TI  - Reactivation of heterodimer and individual subunits of penicillin acylase from E.
      coli after inactivation in urea.
AB  - Individual subunits of penicillin acylase from E. coli were isolated by gel
      filtration under denaturing conditions (8 M urea). Recovery of the catalytic
      activity of the penicillin acylase heterodimer was studied after removal of urea.
      In the case of the heterodimer, 40-60% of the initial activity was recovered,
      whereas the activity of individual subunits was not recovered. Combination of
      native enzyme subunits with subunits isolated from the enzyme pre-inactivated
      with the irreversible inhibitor phenylmethylsulfonyl fluoride resulted in
      heterodimers which were active only in the case of involvement of the beta
      subunit of the active enzyme.

PMID- 10887286
TI  - Structure of an acidic O-specific polysaccharide of the bacterium Providencia
      alcalifaciens O7.
AB  - An acidic O-specific polysaccharide was obtained by mild acid degradation of the
      lipopolysaccharide of the bacterium Providencia alcalifaciens O7 and purified by
      gel chromatography followed by anion-exchange chromatography. On the basis of
      full acid hydrolysis, methylation, carboxyl reduction, selective cleavage with
      anhydrous hydrogen fluoride, and 1H- and 13C-NMR spectroscopy, including two
      dimensional 1H,1H homonuclear and H-detected 1H,13C heteronuclear correlation
      spectroscopy and nuclear Overhauser effect spectroscopy (NOESY), the following
      structure of the linear tetrasaccharide repeating unit of the polysaccharide was
      established: [figure], where Rhap2Ac is 2-O-acetylrhamnopyranose.

PMID- 10887287
TI  - Influence of dinitroglycerol and nitroethyleneglycol lipid derivatives on
      spectral parameters of human hemoglobin.
AB  - The interaction of organic nitrates (nitroethyleneglycol, dinitroglycerol, and
      their esters with arachidonic acid) with oxyhemoglobin and methemoglobin has been
      studied. Addition of nitroethyleneglycol and dinitroglycerol to oxyhemoglobin is
      accompanied by a modest but significant increase in oxidation rate of the heme
      protein to the high-spin ferri-form--methemoglobin. Arachidonoylglycerol
      dinitrate exerts a similar but more pronounced effect on hemoglobin: a molar
      excess of this dinitrate induces the transformation of a significant portion of
      oxyhemoglobin to methemoglobin, whereas arachidonoylnitroethyleneglycol is
      inactive. Arachidonoylglycerol dinitrate also induces changes in the spectral
      characteristics of methemoglobin; this may be due to disintegration of the
      methemoglobin with the loss of heme. The data demonstrate that some organic
      nitrates can interact with hemoglobin; this should be taken into account when
      using the oxyhemoglobin technique for measuring nitric oxide generation from
      these compounds.

PMID- 10887288
TI  - A role of iron ions in the SOS DNA repair response induced by nitric oxide in
      Escherichia coli.
AB  - An induction of the SOS DNA repair response by physiological nitric oxide donors
      (dinitrosyl iron complexes (DNIC) with thiols and S-nitrosothiols (RSNO)) was
      studied in E. coli cells. DNIC with thiols were the most effective SOS-inducers.
      Being more toxic, RSNO mediated a similar response at 10-100 microM, but they
      were inactive at concentrations above 0.5 mM. Pretreatment of the cells with
      chelating agents, o-phenanthroline and picolinic acid, prevented induction of the
      SOS response by all NO-donors used and led to a decrease in the DNIC-type EPR
      signal that appeared after incubation of the cells with DNIC or S
      nitrosoglutathione (GSNO). Analysis of these effects revealed a dual role of iron
      ions in reactivity and toxicity of the NO-donating agents. On one hand, they
      could stabilize GSNO in the form of less toxic DNIC, and, on the other hand, they
      took part in the formation of the SOS-inducing signal by NO-donating agents.

PMID- 10887289
TI  - CN(-)-Induced degradation of nuclei in cells of pea leaves.
AB  - Degradation of nuclei in epidermal and guard cells of pea leaves was induced by
      NaCN. Guard cells were considerably more resistant to CN- than epidermal cells.
      CN--induced nucleus degradation in guard cells was accelerated by illumination.
      The effect of illumination was negligible in epidermal cells that, unlike guard
      cells, do not contain chloroplasts. These data may indicate a role of
      chloroplasts in CN--induced cell death. CN--induced nucleus degradation in
      epidermal cells was retarded by antioxidants (butylated hydroxytoluene and
      vitamin E). The effect of CN- in guard cells was largely removed by vitamin E.
      Salicylic acid, an inhibitor of catalase and ascorbate peroxidase, induced 100%
      degradation of nuclei in epidermal cells but did not significantly affect nuclei
      in guard cells. CN--induced inhibition of catalase and peroxidase is assumed to
      lead to generation and accumulation of reactive oxygen species inducing
      apoptosis. Like mitochondria, which play an important role in animal cell
      apoptosis, chloroplasts may take part in apoptosis in plant cells.

PMID- 10887290
TI  - Sphingolipids of transplantable rat nephroma-RA.
AB  - Contents of sphingolipids (ceramide, sphingomyelin, gangliosides) and the
      composition of their sphingoid bases were studied in the transplantable rat
      nephroma-RA and in rat kidneys. The content of sphingomyelin was about 1.3-fold
      decreased and the content of ceramide was about 1.4-fold increased in the
      nephroma compared to normal kidneys, and this correlated with a 1.4-fold
      increased activity of neutral sphingomyelinase; however, the activity of the
      acidic isoform of the enzyme was virtually unchanged. The content of gangliosides
      was also increased in the nephroma. Ceramide and sphingomyelin of the nephroma,
      in addition to sphingosine, contained a significant amount of sphinganine,
      although a considerable amount of the latter was also found in the renal
      ceramide. The ratio sphingosine/sphinganine in sphingomyelins changed from 65:1
      in kidneys to 5:1 in the nephroma. Thus, the biosynthesis of sphingoid bases
      seems to be disturbed in the transplantable rat nephroma-RA compared to normal
      kidneys.

PMID- 10887291
TI  - Mn-peroxidase from Bjerkandera adusta 90-41. Purification and substrate
      specificity.
AB  - Mn-peroxidase has been purified to homogeneity from culture liquid of white-rot
      fungus Bjerkandera adusta 90-41 grown on medium containing lignosulfonates.
      According to the data on SDS-PAGE and isoelectrofocusing, the molecular mass of
      the enzyme is 43 kD and the isoelectric point is 3.5. The pH-optimum in the
      reaction of MnSO4 oxidation is 4.5. The substrate specificity of the enzyme has
      been studied. In contrast to previously known Mn-peroxidases from B. adusta, the
      isolated enzyme has no activity with veratryl alcohol. The enzyme can oxidize
      ammonium 2, 2-azino-bis(ethyl-6-benzothiazoline sulfonate) (ABTS), o
      phenylenediamine, and phenol red in the absence of Mn2+. Oxidation of ABTS and o
      phenylenediamine is stimulated by Mn2+, whereas in the reaction of oxidation of
      phenol red Mn2+ acts as an inhibitor. Some aromatic substrates, such as
      pyrocatechol and guaiacol, are oxidized only in the presence of Mn2+.

PMID- 10887292
TI  - Fluorogenic substrates for assay of chymosin.
AB  - The use of fluorogenic substrates with intramolecular fluorescence quenching as
      substrates for chymosin was studied. It was shown that chymosin hydrolyzes the
      Phe-Phe peptide bond. The effect of pH on the hydrolysis of substrates by
      chymosin was investigated. The catalytic characteristics of the hydrolysis of the
      fluorogenic substrates were obtained at the pH optima. The influence of
      dimethylformamide on chymosin activity was studied.

PMID- 10887293
TI  - Expression of CYP1A in liver of A/Sn and CC57BR mice differing in sensitivity to
      hepatocarcinogenesis induced by o-aminoazotoluene.
AB  - The induction of P450 cytochromes Cyp1a1 and Cyp1a2 in the liver of male mice
      differing in sensitivity to the carcinogenic effect of o-aminoazotoluene (OAT)
      has been studied. The level of Cyp1a1 and Cyp1a2 mRNA was assayed by quantitative
      competitive polymerase chain reaction (PCR). In both OAT-treated strains, the
      level of Cyp1a1 mRNA increased more than 1000-fold, while the amount of Cyp1a2
      mRNA increased only two- or threefold. Interstrain differences in the Cyp1a mRNA
      level were revealed. The level of Cyp1a1 mRNA in liver of OAT-induced A/Sn mice
      was three times higher than in CC57BR mice. The amount of Cyp1a2 mRNA in control
      and OAT-treated mice was 7 and 13 times higher, respectively, than in CC57BR
      mice. The enzyme activities of cytochromes P450 1a were assayed. An increase in
      Cyp1a1 mRNA level in OAT-treated mice correlated with an enhancement of the
      benzo[a]pyrene hydrolase and 7-ethoxyresofurin o-deethylase activities; the
      correlation between the level of Cyp1a2 mRNA and 7-ethoxyresofurin o-demethylase
      activity was much less pronounced. Interstrain variation in Cyp1a1 and Cyp1a2
      activities was also shown at the enzyme activity level. We suppose that
      quantitative differences in the Cyp1a2 mRNA level play a key role in OAT-induced
      hepatocarcinogenesis.

PMID- 10887294
TI  - Enzymes secreted by filamentous fungi: regulation of secretion and purification
      of an extracellular protease of Trichoderma harzianum.
AB  - Extracellular proteases secreted by the filamentous fungus Trichoderma harzianum
      have been identified. A proteinase active towards Z-Ala-Ala-Leu-pNa--the
      substrate of subtilisin-like proteases--dominated in the culture medium. This
      proteinase is synthesized de novo in response to addition of a protein substrate
      to the medium. Changing the carbohydrate in the culture medium changed the
      quantitative and qualitative spectrum of secreted enzymes. The most active
      extracellular proteinase of Trichoderma harzianum was purified 322-foldfrom the
      culture medium and obtained with a yield of 7.2%. The molecular mass of this
      proteinase is 73 kD and its pI is 5.35. The isolated enzyme has two distinct
      activity maxima, at pH 7.5 and 10.0, and is stable in the pH range 6.0-11.0. The
      temperature optimum for enzyme activity is 40 degrees C at pH 8. 0. The
      proteinase is stable up to 45-50 degrees C (depending on the substrate used).
      Calcium ions stabilized the enzyme at 55-60 degrees C. According to data on the
      study of functional groups of the active center and substrate specificity, the
      enzyme isolated from the culture medium of Trichoderma harzianum is a subtilisin
      like serine proteinase.

PMID- 10887295
TI  - Photoelectric response generated under non-heme iron reduction on the photosystem
      II acceptor side.
AB  - Proteoliposomes containing oxygen-evolving particles of Photosystem II and
      associated with a planar phospholipid membrane generate a transmembrane electric
      potential difference (DeltaPsi) induced by a laser flash. With direct
      electrometrical technique, it was shown that the direction of the electrical
      field ("minus" inside the proteoliposome) corresponds to acceptor side of the
      Photosystem II complex facing inside and donor side facing outside of the
      liposomes. In addition to the fast phase (tau < 0.1 microsec) of the DeltaPsi
      generation due to electron transfer between YZ of the water-oxidizing complex and
      the primary plastoquinone QA, a phase with tau approximately 120 microsec and
      maximum amplitude approximately 30% of the amplitude of the fast phase was
      observed under the first flash in proteoliposomes containing potassium
      ferricyanide, which is known as an oxidant of the non-heme iron (Fenh) on the
      acceptor side of Photosystem II. This additional phase was absent under the
      second laser flash but was completely restored after 5 min dark adaptation. The
      phase of the photoelectric response with tau approximately 120 microsec is
      probably due to electron transfer from QA to Fenh(III) and likely includes a
      component related to H+ transfer.

PMID- 10887296
TI  - Cytotoxic action of conjugates of alpha-fetoprotein and epidermal growth factor
      with photoheme, chlorines, and phthalocyanines.
AB  - Covalently bound conjugates of alpha-fetoprotein (AFP) and epidermal growth
      factor (EGF) with photoheme (PH), 3-desvinyl-3-formylchlorine p6 (Chl p6),
      chlorine e6 (Chl e6), aluminum disulfochloride phthalocyanine (PC(Al)), and
      cobalt octa-4,5-carboxyphthalocyanine (teraphthal, TP(Co)) were synthesized.
      Their molar ratios were 1:4 for AFP-cytotoxin conjugates (cf. 1:10 for AFP
      TP(Co)) and 1:2 for EGF conjugates (cf. 1:1 for EGF-PC(Al)). Dark toxicity of
      both protein conjugates with PH, chlorines, and PC(Al) was much lower than their
      phototoxicity. Studies on phototoxicity demonstrated that PC(Al) conjugates with
      AFP and EGF and also EGF-Chl p6 were the most effective. The cytotoxic activity
      (CTA) of AFP-PC(Al) and EGF-Chl p6 was 80% and of EGF-PC(Al) 64% higher than the
      CTA of the free drugs. Conjugates with TP(Co) were much more toxic on their
      activation with ascorbic acid (AA): in the presence of AA the CTA of AFP-TP(Co)
      and of EGF-TP(Co) was 19 and 61.1% higher, respectively, than the CTA of the free
      TP(Co).

PMID- 10887297
TI  - Light-induced processes of cell protection against photodamage.
AB  - The processes of light-induced cell protection against photodamage, including DNA
      photorepair with involvement of photolyases and photoactivation of enzymatic
      synthesis of photoprotectors and antioxidants (flavonoids, carotenoids, melanins,
      serotonin, and hemoxygenase), are discussed. Mechanisms of photoprotective
      effects against photodynamic oxidation of membrane components and photodamage of
      DNA are analyzed.

PMID- 10887299
TI  - New directions in allergic diseases: mechanism-based anti-inflammatory therapies.
AB  - Advances in our understanding of allergic inflammation have led to the
      development of several novel anti-inflammatory drugs that target specific aspects
      of the inflammatory process. These treatments are based on improvements in
      existing therapies or on a better understanding of the cellular and molecular
      mechanisms involved in atopic diseases. Although most attention has been focused
      on asthma, treatments that inhibit the atopic disease process would have
      application to all atopic diseases, which often coincide. Specific agents that
      are now in development for the treatment of allergic inflammation include
      inhibitors of eosinophilic inflammation (eg, anti-IL-5, CCR3 antagonists, and
      very late antigen 4 inhibitors), drugs that may inhibit allergen presentation,
      and inhibitors of T(H)2 cells. More general anti-inflammatory approaches include
      novel cortico-steroids, phosphodiesterase inhibitors, and mitogen-activated
      protein kinase inhibitors. Most of the new therapies in development are aimed at
      inhibiting or suppressing components of the allergic inflammatory response, but
      in the future, there are possibilities for development of preventive and curative
      treatments.

PMID- 10887300
TI  - Monitoring the patient with asthma: an evidence-based approach.
AB  - The monitoring of symptoms, airflow obstruction, and exacerbations is essential
      to asthma management. Patients who practice self-monitoring in conjunction with
      use of a written action plan and regular medical review have significantly fewer
      hospitalizations, emergency department visits, and lost time from work. Either
      symptom monitoring or peak expiratory flow monitoring is satisfactory, provided
      the results are interpreted with reference to the patient's own baseline asthma
      status. Regular monitoring by physicians also improves health outcomes for
      patients, provided the physician is systematic and monitors control, medications,
      and skills at regular intervals. Additional monitoring tools are under
      evaluation, and these include measures of airway responsiveness, airway
      inflammation, and Internet-based monitoring systems. Administrators need to
      monitor the quality and cost of care, as well as compliance with national
      management guidelines. Assessment of the hospitalization rate and regular audit
      may achieve these aims in the hospital setting. The best way to assess and
      monitor asthma in primary care remains an unresolved yet crucial issue because
      primary care physicians manage the vast burden of illness caused by asthma.
      Monitoring asthma outcomes is an essential step toward the successful
      implementation of national guidelines for the management of asthma.

PMID- 10887301
TI  - Molecular and biochemical classification of plant-derived food allergens.
AB  - Molecular biology and biochemical techniques have significantly advanced the
      knowledge of allergens derived from plant foods. Surprisingly, many of the known
      plant food allergens are homologous to pathogenesis-related proteins (PRs),
      proteins that are induced by pathogens, wounding, or certain environmental
      stresses. PRs have been classified into 14 families. Examples of allergens
      homologous to PRs include chitinases (PR-3 family) from avocado, banana, and
      chestnut; antifungal proteins such as the thaumatin-like proteins (PR-5) from
      cherry and apple; proteins homologous to the major birch pollen allergen Bet v 1
      (PR-10) from vegetables and fruits; and lipid transfer proteins (PR-14) from
      fruits and cereals. Allergens other than PR homologs can be allotted to other
      well-known protein families such as inhibitors of alpha-amylases and trypsin from
      cereal seeds, profilins from fruits and vegetables, seed storage proteins from
      nuts and mustard seeds, and proteases from fruits. As more clinical data and
      structural information on allergenic molecules becomes available, we may finally
      be able to answer what characteristics of a molecule are responsible for its
      allergenicity.

PMID- 10887302
TI  - Gee whiz: CpG DNA allergy therapy!

PMID- 10887303
TI  - The use of standardized extracts in allergen immunotherapy.
AB  - BACKGROUND: Double-blind, placebo-controlled studies have established that
      injection allergen immunotherapy is clinically effective. However, it is not
      known to what extent the doses of allergen extract commonly used in clinical
      practice match those that have been used in these controlled studies. OBJECTIVE:
      The aim of this study was to determine by questionnaire the doses of standardized
      allergen extracts commonly used by board-certified allergists in the United
      States and to compare these with doses that have proven effective in double
      blind, placebo-controlled studies. METHODS: A questionnaire containing a
      hypothetical case and asking for a recommended allergen prescription for
      maintenance immunotherapy was mailed to 500 randomly selected board-certified
      members of the American Academy of Allergy, Asthma and Immunology living in the
      United States. The recommended doses were compared with those doses of the
      extracts that had been proven effective by using major allergen content figures
      for representative standardized US allergen extracts provided by an allergy
      extract laboratory. RESULTS: Responses were received from 118 (23%) of the
      addressees. Eighty (16%) contained interpretable data on maintenance dosing for
      extracts. The median doses of pollen recommended were comparable with those that
      have been demonstrated to be clinically effective. Median doses of house dust
      mites were only slightly lower than those that have proven effective. Median
      doses of animal dander, on the other hand, were well below those used effectively
      in controlled studies. Although the median doses used were often in the range of
      proven doses, the range of doses recommended by allergists included some that
      were one tenth to one five hundredth those of the median doses. CONCLUSION: In
      the absence of useful guidance from the federal regulatory authorities, American
      allergists, for the most part, use doses of pollens and house dust mites that are
      within the proven range. Their dosing of animal dander is generally below proven
      effective doses. There is, however, a wide range of dosing of all extracts used,
      and there is use of mixes that have no botanical basis. Therefore there is need
      for studies defining what are effective and ineffective allergen extract doses.

PMID- 10887304
TI  - Local synthesis of epsilon germline gene transcripts, IL-4, and IL-13 in allergic
      nasal mucosa after ex vivo allergen exposure.
AB  - BACKGROUND: The production of epsilon germline gene transcripts
      (Iepsilon(+)/Cepsilon(+) RNA) precedes class switch recombination to IgE and is
      induced by IL-4 and/or IL-13. Although Iepsilon and Cepsilon RNA(+) B cells have
      been identified within nasal tissue after in vivo allergen exposure, suggesting
      local germline transcription, whether these were resident or infiltrating B
      lymphocytes was not clear. OBJECTIVE: We sought to examine whether B cells
      resident to the nasal mucosa undergo epsilon germline transcription. METHODS:
      Nasal mucosal biopsy specimens were obtained from asymptomatic patients with
      seasonal allergic rhinitis and exposed to allergen ex vivo. Using
      immunocytochemistry, B lymphocytes were enumerated; with in situ hybridization,
      the number of cells expressing Iepsilon, Cepsilon, IL-4, and IL-13 messenger
      (m)RNA(+) cells was examined. RESULTS: Tissue cultured in medium containing
      specific allergen exhibited significantly more Iepsilon and Cepsilon RNA(+) cells
      compared with medium alone (P <.05). IL-4 and IL-13 mRNA synthesis also resulted
      from ex vivo allergen exposure; there were significantly more cells expressing
      transcripts for these cytokines within allergic nasal mucosal tissue cultured
      with allergen than medium alone (P <.05). Within allergen-stimulated tissue
      obtained from allergic patients, 30% of total B cells were Iepsilon RNA(+), and
      the majority of IL-4 and IL-13 mRNA(+) cells were T cells (68% and 44%,
      respectively) and mast cells (32% and 19%, respectively). CONCLUSION: These
      results demonstrate that the nasal mucosa is a site of epsilon germline gene
      transcription and suggest that local T cell and mast cell production of IL-4 and
      IL-13 may regulate this event.

PMID- 10887305
TI  - Genetics of peanut allergy: a twin study.
AB  - BACKGROUND: The role of genetics in the etiology of peanut allergy is unknown.
      For complex genetic traits, twin studies can provide information on the relative
      contribution of genetic factors to a disease, as the relative confounding effects
      of environmental factors are markedly decreased. OBJECTIVE: This study was
      performed to search for evidence that genetic factors influence peanut allergy by
      comparing the concordance rate for this allergy among monozygotic and dizygotic
      twins. METHODS: Twin pairs with at least one member with peanut allergy were
      ascertained through the Food Allergy Network by advertisements in the
      organization's newsletters and Web site. Individuals with peanut allergy or
      parental surrogates were interviewed by telephone. A full atopic history was
      obtained, and peanut allergy and zygosity were determined using previously
      validated questionnaires. Heritability of peanut allergy was determined using
      univariate genetic model fitting by maximum likelihood with the Mx statistical
      modeling software package. RESULTS: Seventy-five twin pairs were recruited.
      Seventeen pairs were excluded because of unconvincing peanut allergy histories (9
      pairs, including 4 of uncertain zygosity) or because one twin had reportedly
      never ingested peanut (8 pairs). The median age of the 58 remaining twin pairs
      was 5 years (range 1 to 58 years). Seventy individuals had peanut allergy. In
      addition to convincing histories of peanut allergy, 52 (74%) had been tested
      (skin prick testing with or without radioallergosorbent assay) and all had
      positive reactions to peanut. Twenty-nine of the 70 had experienced >1 reaction
      to peanut; 29 of 70 had multisystem reactions. Among the monozygotic pairs (n =
      14), 9 were concordant for peanut allergy (pairwise concordance, 64.3%) and among
      dizygotic pairs (n = 44), 3 were concordant for peanut allergy (pairwise
      concordance, 6.8%; chi(2) = 21.38, P <.0001). Heritability of peanut allergy was
      estimated at 81. 6% (95% confidence interval 41.6% to 99.7%) with model fitting
      using a population prevalence of peanut allergy of 0.4%. CONCLUSIONS: The
      significantly higher concordance rate of peanut allergy among monozygotic twins
      suggests strongly that there is a significant genetic influence on peanut
      allergy.

PMID- 10887306
TI  - Mast cell tryptase release and asthmatic responses to allergen increase with
      regular use of salbutamol.
AB  - BACKGROUND: Increased asthmatic responses to allergen, both early and late, have
      been demonstrated after regular use of beta(2)-agonists in as few as 7 days.
      Desensitization of beta(2)-adrenergic receptors on airway mast cells may
      contribute to this effect by allowing greater release of mast cell mediator on
      allergen-induced degranulation. Tryptase released from lung mast cells can be
      measured in serum 1 hour after allergen challenge and serves as a marker of mast
      cell degranulation. OBJECTIVE: To examine the effect of regular treatment with
      salbutamol, a beta(2)-agonist, on mast cell mediator release after allergen
      challenge and its influence on the early asthmatic response (EAR) and the late
      allergic response, we measured the EAR, serum tryptase levels, the 7-hour FEV(1),
      and sputum tryptase levels and cell profiles. METHODS: We conducted a placebo
      controlled, double-blind, randomized cross-over comparison of treatments for 10
      days with either a salbutamol metered-dose inhaler (100 microgram, 2 puffs 4
      times daily) or a matched placebo inhaler with at least a 7-day washout between
      treatments. Atopic subjects (n = 14) with mild-to-moderate asthma performed same
      dose allergen inhalation tests after both treatments 12 to 15 hours after the
      last dose of study inhaler. Baseline and 7-hour FEV(1) and the EAR to allergen
      were measured by using spirometry; venous blood was drawn at 1 hour for analysis
      of serum tryptase; and sputum was induced and collected at 1 and 7 hours.
      RESULTS: Salbutamol treatment resulted in a significantly greater EAR (20% +/-
      1.6% [SEM] vs 15% +/- 2.1%; P =.047); increased 1-hour serum tryptase levels
      (9.09 +/- 1.57 vs 7.52 +/- 1.12 microgram/L; P =. 011); increased proportions of
      eosinophils in the 7-hour sputum sample (39.1% +/- 5.1% vs 28.4% +/- 4.4%; P
      <.05); increased proportion of metachromatic cells in the 7-hour sputum sample
      (4.4% +/- 1.1% vs 2.2% +/- 0.6%; P =.032); and lower 7-hour FEV(1) (2.77 +/- 0.18
      vs 2.97 +/- 0.20 L; P =.014). Baseline FEV(1) was not significantly different
      after salbutamol treatment compared with values after placebo treatment (2.90 +/-
      0.20 vs 3.00 +/- 0.19 L; P =.11). CONCLUSION: Regular 10-day treatment with
      salbutamol increases the allergen-induced release of mediator from airway mast
      cells, and this is reflected in an increased EAR to allergen. Late-phase
      responses to allergen were also enhanced, as demonstrated by decreased 7-hour
      FEV(1) and increased eosinophilia and percentage of metachromatic cells in the 7
      hour sputum sample. Increased allergen-induced mast cell degranulation could, in
      part, explain the increased asthmatic responses to allergen after beta(2)-agonist
      treatment and could contribute to the deterioration of asthma control that is
      associated with regular use of beta(2)-agonist by potentiating allergic
      inflammation.

PMID- 10887307
TI  - Histamine and tryptase levels in patients with acute allergic reactions: An
      emergency department-based study.
AB  - BACKGROUND: Emergency department visits for acute allergic reactions are common.
      Although the diagnosis and classification of these allergic reactions is
      primarily empiric, it is not always clear whether certain signs and symptoms
      constitute systemic mediator release syndromes, such as anaphylaxis, and thus may
      warrant more aggressive therapy or follow-up. OBJECTIVE: We sought to determine
      associations between various clinical signs and symptoms with both plasma
      histamine levels and serum tryptase levels in adult patients presenting to an
      emergency department with acute allergic syndromes. The clinical correlates of
      raised beta-tryptase levels were also investigated. METHODS: Ninety-seven adult
      emergency department patients were prospectively studied by using a
      questionnaire, physical examination, and serum-plasma sampling. Plasma histamine
      and serum total and beta-tryptase levels were determined. Clinical groupings were
      compared for mediator levels by using simple and multivariate analysis. RESULTS:
      Elevated levels of plasma histamine (>10 nmol/L) and serum total tryptase (>15
      ng/mL) were observed in 42 and 20 patients, respectively. Detectable beta
      tryptase (>/=1 ng/mL) was observed in 23 patients, including 15 of the patients
      with elevated total tryptase levels. Suspected food allergy incidences and the
      duration of reaction were similar in patients with increased histamine levels and
      in patients with increased tryptase levels. Increased total tryptase levels,
      histamine levels, or both were observed in some patients who did not have airway,
      cardiovascular, or abdominal signs. Histamine levels correlated better with
      clinical signs than tryptase levels. Histamine elevations (>10 nmol/L) were
      observed more frequently in patients characterized by the following clinical
      signs in univariate analysis: the presence of urticaria, more extensive erythema,
      abnormal abdominal findings, and wheezing. Total tryptase increases were observed
      more frequently only in patients with urticaria. Histamine levels correlated with
      initial heart rates. In multivariate analysis the extent of urticaria was the
      best single predictor of plasma histamine levels and of either an elevated
      histamine or tryptase level. Detectable beta-tryptase levels were observed in
      some patients who had neither elevated total tryptase nor elevated histamine
      levels. Unlike patients without detectable beta-tryptase levels, patients who had
      detectable beta-tryptase levels had a significant correlation between total
      tryptase and histamine levels (P <.05). CONCLUSIONS: Raised histamine and, less
      commonly, raised tryptase levels are observed in almost 50% of patients
      presenting to emergency departments with acute allergic reactions. Some cases
      associated with systemic mediator release do not have classical features of
      severe anaphylaxis, such as hypotension or tachycardia. The lack of total
      tryptase elevations in many patients with elevated plasma histamine levels
      suggests basophil involvement. The clinical utility of beta-tryptase
      determinations in the evaluation of acute allergic reactions needs further study.

PMID- 10887308
TI  - 5' flanking region polymorphism of the gene encoding leukotriene C4 synthase does
      not correlate with the aspirin-intolerant asthma phenotype in the United States.
AB  - BACKGROUND: Approximately 10% of patients with asthma have a distinct clinical
      entity in which their symptoms are exacerbated by aspirin and most other
      nonsteroidal anti-inflammatory agents. These individuals typically have
      significant basal overproduction of cysteinyl leukotrienes, and within their
      biosynthetic pathway, the terminal enzyme, leukotriene C(4) synthase (LTC(4)S),
      is significantly overexpressed. A single nucleotide polymorphism consisting of an
      adenine (A) to cytosine (C) transversion -444 nucleotides upstream of the ATG
      translation start site in the LTC(4)S gene has been associated with a relative
      risk of 3.89 for the aspirin-intolerant phenotype in Polish patients. OBJECTIVE:
      These studies were undertaken to further investigate the functional effect of
      this allele in LTC(4)S gene expression and subsequently to determine whether an
      association between the presence of this polymorphism and aspirin-intolerant
      asthma existed within patients of the United States. METHODS: Functionality of
      the C-444 allele was assessed by using promoter-reporter constructs and transient
      transfection assays in the THP-1 monocytic cell line. Genotyping was performed on
      137 unaffected control subjects, 33 patients with aspirin-tolerant asthma, and 61
      patients with aspirin-intolerant asthma from the United States. RESULTS: Promoter
      reporter constructs containing the C-444 allele revealed no significant
      upregulatory or downregulatory effects in the transcription of the LTC(4)S gene.
      The LTC(4)S genotype distribution was consistent with the Hardy-Weinberg
      equilibrium in patients with aspirin-tolerant asthma and unaffected control
      subjects but not in patients with aspirin-intolerant asthma; however, the
      distributions were not significantly different among the phenotype groups.
      CONCLUSIONS: Our data demonstrate that the C-444 allele in the LTC4S gene is not
      statistically different among patients with the aspirin-intolerant asthmatic
      phenotype, patients with the aspirin-tolerant asthmatic phenotype, and unaffected
      control subjects in the United States. This finding, along with the lack of
      functionality of this polymorphism, suggest that it is not related to a specific
      asthma phenotype and may represent a population-stratified polymorphism within
      patients of eastern European descent.

PMID- 10887309
TI  - Delayed eosinophil apoptosis in asthma.
AB  - BACKGROUND: Eosinophilic inflammation of the airways is a key characteristic of
      asthma. A defect in apoptosis might contribute to the chronic tissue eosinophilia
      associated with asthma. OBJECTIVE: Our purpose was to examine whether the rate of
      apoptosis differs between peripheral blood eosinophils from asthmatic patients
      and healthy volunteers. METHODS: Peripheral blood was obtained from volunteers
      with asthma and from control volunteers. Eosinophils were isolated by CD16
      negative selection to >99% purity and were cultured for 48 hours. The number of
      apoptotic eosinophils in the culture was assessed by flow cytometric analysis of
      relative DNA content in propidium iodide-stained cells. Eosinophil apoptosis is
      expressed as apoptosis index (number of apoptotic cells/total number of cells).
      RESULTS: Eosinophils from asthmatic patients not taking steroid medication
      survived longer (apoptosis index 0.25) than those of healthy control subjects
      (apoptosis index 0.40, P <.05). In contrast, the rate of apoptosis in eosinophils
      from patients concurrently taking steroids (apoptosis index 0.46) is higher than
      that of those not using steroids (P <.01) and not different from that of healthy
      subjects. To assess whether endogenous IL-3, IL-5, and GM-CSF production
      contributes to the delayed eosinophil apoptosis, the effects of the corresponding
      neutralizing antibodies were studied on eosinophil longevity. Neutralization of
      GM-CSF, but not of IL-3 or IL-5, increased slightly but significantly (P <.01)
      the rate of apoptosis in eosinophils obtained from patients with asthma. To
      assess whether beta(2)-agonist medication could contribute to the observed
      differences, we determined the in vitro effects of albuterol, fenoterol, and
      salmeterol on eosinophil apoptosis. All beta(2)-agonists inhibited eosinophil
      apoptosis by 12% to 19%. A possibility existed that a prior in vivo exposure to
      IL-5, GM-CSF, or beta(2)-agonists would explain the observed difference. To study
      this, eosinophils were incubated with GM-CSF, IL-5, and albuterol for 2 to 3
      hours, followed by washout of the added compounds, and were subsequently cultured
      for 48 hours. However, an exposure to GM-CSF (7 pmol/L) or IL-5 (10 pmol/L) for
      15 to 180 minutes was not a sufficient signal to prevent eosinophil apoptosis. In
      contrast, exposure to albuterol (100 nmol/L) for 120 minutes was sufficient to
      induce a significant (P <.05) decrease in eosinophil apoptosis. CONCLUSIONS: The
      results suggest that eosinophil apoptosis is delayed in asthma. This delay may be
      partly explained by production of GM-CSF. The in vitro effects of beta(2)
      agonists suggest that beta(2)-agonist use might contribute to the prolonged
      eosinophil survival through inhibition of apoptosis and thus may worsen
      eosinophilia in asthmatic patients. Use of inhaled glucocorticoids seems to
      totally reverse the delayed eosinophil apoptosis in asthma.

PMID- 10887310
TI  - PBMCs from both atopic asthmatic and nonatopic children show a TH2 cytokine
      response to house dust mite allergen.
AB  - BACKGROUND: The hypothesis that in atopic diseases the T-helper response is
      skewed toward a T(H)2-type cytokine response was based on studies with mitogen
      stimulation, T-cell clones, or both. OBJECTIVE: Using primary cultures, we
      investigated (1) whether atopic asthmatic patients have a T(H)2 response and
      nonatopic subjects have a T(H)1 response to allergen and (2) whether atopic
      patients have a decreased ability to mount T(H)1 immune responses to
      mycobacterial antigens. METHODS: The responses of PBMCs to allergen (house dust
      mite [HDM]) or purified protein derivative of Mycobacterium tuberculosis (PPD)
      stimulation from 10 severely and 14 moderately asthmatic patients (all allergic
      to HDM) were compared with those of 17 nonatopic healthy black (Xhosa) children.
      RESULTS: HDM-stimulated proliferation, IL-5 release, and the IL-5/IFN-gamma ratio
      were significantly increased in subjects with atopic asthma, whereas IFN-gamma
      release was not significantly different. IL-4 levels were below the level of
      detection. PPD-stimulated proliferation, IL-5 release, IFN-gamma release, and the
      IL-5/IFN-gamma ratio were not significantly different among the groups. Each
      group had a significantly higher IL-5/IFN-gamma ratio in response to HDM than to
      PPD (a T(H)1 stimulus). CONCLUSION: Our study, which used primary cultures to
      investigate the hypothesis that nonatopic subjects have a T(H)1 response to
      allergens, indicates that HDM stimulates a T(H)2 cytokine response in both atopic
      and nonatopic subjects but that the response is enhanced in atopic patients. Our
      results with PPD suggest that normal and atopic asthmatic subjects can have a
      T(H)1 cytokine response to mycobacteria, but there is a subgroup of atopic
      subjects that have a T(H)2 response.

PMID- 10887311
TI  - Interaction of fungal spores with the lungs: distribution and retention of
      inhaled puffball (Calvatia excipuliformis) spores.
AB  - BACKGROUND: The biologic responses to inhaled airborne fungal spores, which are
      well-known allergen carriers, would be better understood if we had an insight
      into their pattern of distribution and interaction with lung structures.
      OBJECTIVES: To investigate the retention characteristics of inhaled
      basidiospores, which often represent the major portion of the spore load in air
      sampling surveys and to analyze their regional distribution within and
      interaction with the lungs. METHODS: Intubated and anesthetized Syrian Golden
      hamsters inhaled aerosols of puffball (Calvatia excipuliformis) spores, with an
      aerodynamic diameter of 3.1 micrometer, either by spontaneous breathing (group A,
      n = 3) or by continuous negative-pressure ventilation (group B, n = 4). Lungs
      were fixed by intravascular perfusion of fixative solution within 29 minutes of
      the initial inhalation, and tissue samples were then processed for light and
      electron microscopy. RESULTS: Stereological (fractionator) analysis of lung
      tissue revealed that the greatest number of spores was deposited within the
      alveoli (67.2% in group A and 89.8% in group B). The intrapulmonary conducting
      airways retained an intermediate proportion (32.3% in group A and 10.0% in group
      B), whereas the extrapulmonary mainstem bronchi and trachea held the lowest
      proportion (0.5% or less). Deposited spores were lodged within the aqueous lining
      layer and in close proximity to the epithelial cells. Within the intrapulmonary
      conducting airways, 22. 3% of the spores in group A and 9.0% of those in group B
      had been engulfed by macrophages. CONCLUSION: This study demonstrates that
      inhaled 3-micrometer-diameter basidiospores become distributed over a large
      surface area. It also reveals that such particles are displaced by surfactant
      (surface forces) into the aqueous lining layer of airways and alveoli, thereby
      facilitating subsequent phagocytosis by macrophages. This interaction of spores
      with lung structures may be important for the development of respiratory
      allergies induced by airborne fungal allergens.

PMID- 10887313
TI  - Monocyte chemoattractant peptide-1 expression during cutaneous allergic reactions
      in mice is mast cell dependent and largely mediates the monocyte recruitment
      response.
AB  - BACKGROUND: Macrophages and infiltrating monocytes comprise the largest
      population of cells within the airways of patients with allergic asthma. Both
      become activated and thus contribute to the pathologic features of allergic
      reactions, but the mechanism by which they are recruited has not been well
      documented. OBJECTIVE: Our purpose was to assess the role of the CC chemokine
      monocyte chemotactic peptide-1 (MCP-1) in monocyte recruitment during allergic
      reactions in mice. METHOD: We used immunohistochemistry and Northern blotting to
      assess MCP-1 expression, selective mast cell reconstitution of mast cell
      deficient W/W(v) mice to demonstrate the mast cell dependence of MCP-1 expression
      and monocyte recruitment and neutralizing anti-MCP-1 antibodies to block monocyte
      recruitment during cutaneous allergic reactions. RESULTS: MCP-1 was expressed
      largely by resident dermal cells within the allergic lesions at 4 hours after
      challenge, followed within several hours by an influx of monocytes; at 10 hours
      after challenge monocytes comprised a substantial proportion of the infiltrating
      cells at the nidus of the response. Mast cell-reconstituted, but not mast cell
      deficient W/W(v) mice expressed MCP-1 transcripts and developed monocyte
      infiltrates after allergen challenge. Finally, anti-MCP-1 antibody treatments
      reduced by approximately 63% the influx of monocytes into the reaction sites.
      CONCLUSIONS: These data clearly demonstrate the mast cell dependence of the MCP-1
      expression and the monocyte influx and establish a substantial, but not
      exclusive, causal relationship between these 2 events.

PMID- 10887312
TI  - Comparison of inflammatory responses to genetically engineered hypoallergenic
      derivatives of the major birch pollen allergen bet v 1 and to recombinant bet v 1
      wild type in skin chamber fluids collected from birch pollen-allergic patients.
AB  - BACKGROUND: Nearly 60% of birch pollen-allergic patients react exclusively to Bet
      v 1. With use of the skin blister model, previously only established for
      installation of crude allergens, we have for the first time characterized the
      inflammatory response in vivo to recombinant birch pollen allergen, rBet v 1,
      molecules (rBet v 1 wild type, fragments and trimer). OBJECTIVE: Our purpose was
      to examine whether challenge with rBet v 1 derivatives (fragments and trimer)
      compared with rBet v 1 wild type differs with respect to influx of activated
      eosinophils and detectable levels of cytokines/chemokines related to allergic
      inflammation in skin chambers applied to birch pollen-allergic patients. METHODS:
      The skin blister chambers were filled for 2 hours with rBet v 1, the derivatives
      or PBS and heparin (negative control). The fluids were analyzed after 2 and 8
      hours. The number of eosinophils was determined and EG2 and CD69 expression
      measured by flow cytometry. Cytokines and mediators were analyzed by ELISA and
      RIA techniques. RESULTS: Comparable numbers of eosinophils were recruited to the
      chambers challenged with rBet v 1 molecules, but the eosinophils from the rBet v
      1 wild-type challenged chambers showed a significantly higher expression of CD69.
      The levels of eotaxin were similar in all 4 chambers, whereas rBet v 1 wild type
      induced significantly higher levels of histamine, eosinophil cationic protein,
      and GM-CSF than the derivatives did. Recombinant Bet v 1 trimer elicited
      significantly lower levels of IL-4 compared with rBet v1 wild type. CONCLUSION:
      Genetically engineered hypoallergenic rBet v 1 derivatives recruited eosinophils
      analogously with rBet v 1 wild type. However, the derivatives exhibited a lower
      capacity to activate eosinophils and to release proinflammatory mediators and T
      helper type 2-derived cytokines. The derivatives may therefore be candidate
      molecules for specific immunotherapy of birch pollen allergy with reduced risk of
      inducing allergenic or inflammatory side effects.

PMID- 10887314
TI  - Bradykinin stimulates eotaxin production by a human lung fibroblast cell line.
AB  - BACKGROUND: Bradykinin, a potent inflammatory peptide, is increased in the
      airways of allergic patients. Accompanying the elevated bradykinin levels are
      increases in both eosinophils and fibroblasts. Eotaxin, a potent eosinophil
      specific chemotactic factor, is released by fibroblasts and increased in the
      lower respiratory tract of allergic patients. OBJECTIVE: We sought to test the
      hypothesis that lung fibro-blasts release eotaxin in response to bradykinin.
      METHODS: The potential of bradykinin to induce the release of eotaxin from the
      human lung fibroblast cell line HFL-1 was tested by cell culture and evaluation
      of the culture supernatant fluids and RNA for immunoreactive eotaxin and eotaxin
      messenger RNA. RESULTS: HFL-1 cells released eotaxin constitutively without
      stimulation, but bradykinin stimulated eotaxin release in a dose- and time
      dependent manner and resulted in augmented expression of eotaxin messenger RNA.
      The release of eotaxin was sensitive to the action of glucocorticoids. Eosinophil
      chemotactic activity by HFL-1 supernatant fluids was inhibited by anti-human
      eotaxin-neutralizing antibody. Consistent with these results, inhibitors of
      bradykinin B2 receptors, but not bradykinin B1 receptors, inhibited bradykinin
      induced eotaxin release. CONCLUSION: These data demonstrate that bradykinin may
      stimulate lung fibroblasts to release eotaxin and suggest the potential for this
      mechanism to be important in modulation of lung inflammation.

PMID- 10887316
TI  - Polymorphisms in the IL4, IL4RA, and FCERIB genes and asthma severity.
AB  - BACKGROUND: Genetic polymorphisms have been associated with asthma and asthma
      severity. OBJECTIVE: We sought to determine whether 3 polymorphisms were
      associated with severe asthma indicated either by the occurrence of a fatal (or
      near-fatal) asthma attack or by severe airflow obstruction. METHODS: We obtained
      DNA and clinical data from asthmatic subjects who either died or nearly died
      during an asthma attack and from a group of subjects with mild-to-moderate asthma
      who had never experienced a fatal or near-fatal asthma episode. These groups were
      compared with a group of nonatopic nonasthmatic control subjects. The level of
      airflow obstruction (FEV(1) percent predicted) in the subjects with mild-to
      moderate asthma was used as an additional measure of disease severity. The
      subjects were genotyped for the IL4*C-589T promoter polymorphism and the
      IL4RA*Q576R and the FCERIB*E237G amino acid substitutions. RESULTS: The results
      showed that the FCERIB*E237G and IL4RA*Q576R polymorphisms were not associated
      with fatal or near-fatal asthma. However, the IL4*-589T allele was significantly
      increased in the subjects with fatal or near-fatal asthma compared with
      nonasthmatic subjects (odds ratio [OR], 1.8; P =.02) and subjects with mild-to
      moderate asthma (OR, 1.9; P =.02). There was no interaction between the IL4*-589T
      and IL4RA*576R alleles. Of the 3 polymorphisms, only the IL4RA*576R allele was
      associated with severe airflow obstruction (OR, 8.2; P =.01). CONCLUSION: These
      data suggest that the IL4*-589T allele is a risk factor for life-threatening
      asthma and that the IL4RA*576R allele is a risk factor for a low level of lung
      function in asthmatic subjects.

PMID- 10887315
TI  - Conjugation of immunostimulatory DNA to the short ragweed allergen amb a 1
      enhances its immunogenicity and reduces its allergenicity.
AB  - BACKGROUND: Allergen immunotherapy is inconvenient and associated with the risk
      of anaphylaxis. Efforts to improve the safety of immunotherapy by means of
      chemical modification of allergens have not been successful because it greatly
      reduced their antigenicity. Recently, immunostimulatory DNA sequences (ISS or CpG
      motifs) have been shown to act as strong T(H)1 response-inducing adjuvants.
      OBJECTIVE: We sought to determine whether conjugation of ISS to the major short
      ragweed allergen Amb a 1 results in enhanced immunotherapeutic potential in mice
      and decreased allergenicity in human subjects. METHODS: A 22-mer ISS
      oligodeoxynucleotide (ISS-ODN) was coupled to Amb a 1 and used for immunization
      of mice, rabbits, and monkeys. RESULTS: In mice the Amb a 1-ISS conjugate induced
      a T(H)1 response (IFN-gamma secretion), whereas Amb a 1 induced a T(H)2 response
      (IL-5 secretion). The T(H)1 response was not observed with an Amb a 1-non-ISS
      conjugate. Coinjection of Amb a 1 with ISS-ODN was much less effective in
      inducing a T(H)1 response. In mice primed for a T(H)2 response, injection with
      Amb a 1-ISS conjugate induced a de novo T(H)1 response and suppressed IgE
      antibody formation after challenge with Amb a 1. Amb a 1-ISS conjugate induced
      high-titer anti-Amb a 1 IgG antibodies in rabbits and cynomolgus monkeys, whereas
      Amb a 1 alone or Amb a 1 coinjected with ISS-ODN did not induce a detectable
      response. Amb a 1-ISS conjugate was less allergenic than Amb a 1 alone, as shown
      by a 30-fold lower histamine release from human basophils of patients with
      ragweed allergy, whereas mixing ISS-ODN with Amb a 1 did not reduce histamine
      release. CONCLUSION: Amb a 1-ISS conjugate has an enhanced T(H)1-biased
      immunogenicity and reduced allergenicity. It may offer a more effective and safer
      approach for allergen immunotherapy than currently available methods.

PMID- 10887317
TI  - Reciprocal regulation of cultured human mast cell cytokine production by IL-4 and
      IFN-gamma.
AB  - BACKGROUND: T(H)1 and T(H)2 cytokines are thought to regulate allergic
      inflammation. OBJECTIVE: Two key regulatory cytokines, IL-4 and IFN-gamma, were
      examined for their effects on cytokine production by cultured human mast cells
      (CHMCs). METHODS: CHMCs were obtained by culturing cord blood-derived CD34(+)
      cells in the presence of stem cell factor and IL-6 for 14 to 16 weeks. CHMCs were
      passively sensitized with human myeloma IgE and supplemented with or without IL-4
      or IFN-gamma. After the sensitization, CHMCs were stimulated with anti
      FcepsilonRIalpha mAb. Concentrations of secreted cytokines were measured by using
      ELISA, and cytokine messenger RNA was analyzed by using quantitative competitive
      RT-PCR. RESULTS: IL-4 profoundly enhanced FcepsilonRI-mediated production of
      macrophage inflammatory protein (MIP) 1alpha, IL-8, and GM-CSF. For example, the
      enhancement by IL-4 (10 ng/mL) of the production of MIP-1alpha, IL-8, and GM-CSF
      was 25-, 7-, and 90-fold, respectively, after 6 hours. IL-4 also enhanced levels
      of FcepsilonRI-induced cytokine messenger RNA but to a lesser degree. In
      contrast, IFN-gamma inhibited FcepsilonRI-induced production of MIP-1alpha, IL-8,
      and GM-CSF. For example, the inhibition by IFN-gamma (10 ng/mL) of FcepsilonRI
      mediated production of MIP-1alpha, IL-8, and GM-CSF was 80%, 75%, and 95%,
      respectively. IFN-gamma also suppressed FcepsilonRI-induced messenger RNA
      expression of these cytokines. Neither IL-4 nor IFN-gamma affected the kinetics
      of cytokine production by CHMCs. CONCLUSION: These data suggest that IL-4 and IFN
      gamma may influence allergic reactions by modulating human mast cell cytokine
      production.

PMID- 10887318
TI  - A murine model of peanut anaphylaxis: T- and B-cell responses to a major peanut
      allergen mimic human responses.
AB  - BACKGROUND: Peanut allergy affects 0.6% of the US population. At the present
      time, allergen avoidance is the only therapeutic option. Animal models of food
      induced anaphylaxis would facilitate attempts to design novel immunotherapeutic
      strategies for the treatment of peanut allergy. OBJECTIVE: The purpose of this
      study was to develop a murine model of IgE-mediated peanut hypersensitivity that
      closely mimics human peanut allergy. METHODS: C3H/HeJ mice sensitized orally with
      freshly ground whole peanut and cholera toxin as adjuvant were challenged orally
      3 and 5 weeks later with crude peanut extract. Anaphylactic reactions were
      determined. T- and B-cell responses to Ara h 1 and Ara h 2, the major peanut
      allergens, were characterized by evaluating splenocyte proliferative responses
      and IgE antibody concentrations. Furthermore, IgE antibodies in the sera of
      patients with peanut allergy and mice were compared for antibody binding to Ara h
      2 isoforms and allergenic epitopes. RESULTS: Peanut-specific IgE was induced by
      oral peanut sensitization, and hypersensitivity reactions were provoked by
      feeding peanut to sensitized mice. The symptoms were similar to those seen in
      human subjects. Ara h 1- and Ara h 2-specific antibodies were present in the sera
      of mice with peanut allergy. Furthermore, these Ara h 2-specific IgE antibodies
      bound the same Ara h 2 isoforms and major allergenic epitopes as antibodies in
      the sera of human subjects with peanut allergy. Splenocytes from mice with peanut
      allergy exhibited proliferative responses to Ara h 1 and Ara h 2. CONCLUSION:
      This murine model of peanut allergy mimics the clinical and immunologic
      characteristics of peanut allergy in human subjects and should be a useful tool
      for developing immunotherapeutic approaches for the treatment of peanut allergy.

PMID- 10887319
TI  - Persimmon leaf extract and astragalin inhibit development of dermatitis and IgE
      elevation in NC/Nga mice.
AB  - BACKGROUND: We previously found that persimmon leaf extract contains antiallergic
      substances that inhibit histamine release by human basophilic cell line KU812 in
      response to cross-linkage of FcepsilonRI. OBJECTIVES: The purpose of this study
      was to identify substances in the persimmon leaf extract that are responsible for
      the effect and to examine their in vivo effects on the allergic mouse model.
      METHODS: HPLC analysis of persimmon leaf extract was done to measure its content.
      Inhibitory activity of persimmon leaf extract or its major constituent of
      flavonoids (astragalin) on the histamine release by KU812 cells was examined. To
      investigate the effects of these substances in vivo, models of passive cutaneous
      anaphylaxis and atopic dermatitis mice (NC/Nga) were used. RESULTS: Persimmon
      leaf extract or astragalin inhibited histamine release from KU812 in response to
      cross-linkage of FcepsilonRI. Oral intake of both substances dose dependently
      inhibited passive cutaneous reactions. Moreover, oral administration of these
      substances to NC/Nga atopic dermatitis-model mice led to a striking suppression
      of the development of dermatitis, scratching behavior, and serum IgE elevation.
      Histologic analyses revealed that infiltration of inflammatory cells, especially
      degranulated mast cells, thickening of the epidermis, and prominent
      hyperkeratosis, were significantly reduced. Immunologic studies showed that the
      capacity of spleen T cells to produce both IL-4 and IL-13, but not IFN-gamma, was
      downregulated by means of oral intake of these substances. CONCLUSION: This study
      demonstrates a novel activity of astragalin and the dramatic effect of persimmon
      leaf extract and astragalin on atopic dermatitis-model mice.

PMID- 10887320
TI  - An IL13 coding region variant is associated with a high total serum IgE level and
      atopic dermatitis in the German multicenter atopy study (MAS-90).
AB  - BACKGROUND: Allergic diseases are one of the major causes of morbidity in the
      developed countries today, and the prevalence of these diseases is increasing
      steadily. Study of total serum gE level is important in understanding the
      genetics of allergic iseases because IgE levels are considered to be a crucial
      pathogenic component. IL-13 plays an important role in the induction of IgE
      synthesis and in the pathogenesis of allergic diseases. OBJECTIVE: We sought to
      examine potential variation at the IL13 gene and estimate its effect on elevated
      IgE level and atopic dermatitis (AD). METHODS: We conducted mutational analyses
      of the IL13 gene by using single-stranded conformation polymorphism and DNA
      sequencing. Case control studies for high-IgE phenotype and AD were performed by
      using subjects from the German MAS-90 cohort. RESULTS: A novel IL13 coding region
      variant at 4257 bp (G to A, fourth exon) was identified. Case control studies of
      a German sample from the MAS-90 cohort showed significant associations between
      the presence of the A allele and two atopic phenotypes: high IgE (odds ratio,
      2.38; 95% confidence interval, 1.35-4.21; P =.0026) and AD (odds ratio, 1.77; 95%
      confidence interval, 1.06-2.96; P =.03). CONCLUSION: This IL13 coding region
      variant may be involved in the pathogenesis of AD and high total serum IgE level
      in a study population of white subjects.

PMID- 10887321
TI  - First aid anaphylaxis management in children who were prescribed an epinephrine
      autoinjector device (EpiPen).
AB  - BACKGROUND: Epinephrine for first aid use by parents and other caregivers and in
      the form of an autoinjector device (EpiPen, Center Laboratories) is often
      prescribed for children who have had previous anaphylactic reactions. It is not
      known whether the EpiPen device is used appropriately during subsequent reactions
      and whether its use is able to prevent the complications of anaphylaxis.
      OBJECTIVE: Our purpose was to determine parental knowledge and practice
      concerning first aid anaphylaxis management, the frequency of recurrent
      generalized allergic reactions, the first aid measures taken, and the subsequent
      outcome of these reactions. METHODS: A retrospective survey was performed with a
      telephone questionnaire of all children with a history of anaphylaxis who
      attended a specialist allergy service and were prescribed an EpiPen autoinjector
      device. RESULTS: Recurrent generalized allergic reactions occurred with a
      frequency of 0.98 episodes per patient per year and were more common in those
      with food compared with insect venom anaphylaxis. The EpiPen device was only used
      in 29% of recurrent anaphylactic reactions. Parental knowledge was deficient in
      recognition of the symptoms of anaphylaxis and use of the EpiPen device, and
      adequate first aid measures were not in place for the majority of children
      attending school. Those children in whom the EpiPen device was used were less
      likely to be given epinephrine in hospital and to require subsequent hospital
      admission. CONCLUSION: The EpiPen autoinjector device is infrequently used in
      children with recurrent episodes of anaphylaxis; the reasons for this require
      further research. It is likely that parents and other caregivers will require
      continuing education and support in first aid anaphylaxis management. When the
      EpiPen device is used appropriately, it appears to reduce subsequent morbidity
      from anaphylaxis.

PMID- 10887322
TI  - Isolation and characterization of a major allergen from the fish parasite
      Anisakis simplex.
AB  - BACKGROUND: Ingestion of raw or undercooked fish can lead to infection of human
      subjects by the fish parasite Anisakis simplex, a disease known as anisakiasis or
      anisakidosis. Patients sensitized to this fish parasite show high levels of total
      and specific IgE. Cross-reactions seem to explain the fact that specific IgE
      antibodies are also found in a high number of normal subjects, as reported in
      other parasitoses. OBJECTIVE: We sought to purify and characterize a major IgE
      binding protein from the parasite. METHODS: A protein was purified from the crude
      parasite extract by means of ethanol precipitation and reversed-phase HPLC. Its
      clinical relevance was tested on 20 parasite-positive sera by using IgE and IgG4
      immunoblotting. A monospecific human serum was used to study its localization in
      the parasite body. RESULTS: A 24-kd protein was purified, to which only 45% of
      the sera had specific IgG4, but 85% of sera had specific IgE. The protein was
      present only in the excretory gland, as shown by immunohistochemistry. N-terminal
      amino acid sequence (17 residues) showed no homology to previously described
      proteins. CONCLUSION: A simplex contains a potent allergen in the excretory
      gland. This major parasite allergen, named Ani s 1, could have important clinical
      relevance, as shown by the high number of positive sera in the specific IgE
      immunoblotting.

PMID- 10887323
TI  - Clinical cross-reactivity among foods of the Rosaceae family.
AB  - BACKGROUND: Foods from the Rosaceae botanical family have been increasingly
      reported as causes of allergic reaction. Patients frequently have positive skin
      tests or radioallergosorbent test results for multiple members of this botanical
      family. OBJECTIVE: Our purpose was to investigate the clinical cross-reactivity
      assessed by double-blind, placebo-controlled food challenge (DBPCFC) of Rosaceae
      foods (apricot, almond, plum, strawberry, apple, peach, and pear). METHODS:
      Thirty-four consecutive adult patients complaining of adverse reactions to
      Rosaceae were included in the study. Skin prick tests and CAP System (FEIA) were
      performed with Rosaceae foods in all patients. Clinical reactivity to Rosaceae
      was systematically evaluated by open food challenges (OFCs), unless there was a
      convincing history of a recent severe anaphylaxis. Positive reactions on OFCs
      were subsequently evaluated by DBPCFCs. RESULTS: Twenty-six and 24 patients had
      positive skin prick tests and CAP FEIA with Rosaceae, respectively; from these
      88% and 100% had positive tests with >/=2. No evidence of clinical reactivity was
      found in 66% percent of positive skin prick tests and 63% of positive specific
      IgE determinations to fruits. A total of 226 food challenges (including OFC and
      DBPCFC) were performed in the 28 patients with positive skin prick tests or CAP
      System FEIA. Of 182 initial OFCs carried out, 26 (14%) reactions were confirmed
      by DBPCFCs. Overall, 40 reactions were considered positive in 22 patients with
      positive skin tests or CAP FEIA. Thirty-eight reactions had been previously
      reported, the remaining two were detected by systematic challenges. Most
      reactions were caused by peach (22 patients), apple (6), and apricot (5). Ten
      patients (46%) were clinically allergic to peach and other Rosaceae. CONCLUSION:
      Positive skin test and CAP System FEIA should not be taken as the only guide for
      multi-species dietary restrictions. Nevertheless, the potential clinical allergy
      to other Rosaceae should not be neglected. If the reported reaction is confirmed,
      current tolerance to other Rosaceae should be precisely established unless there
      has been ingestion without symptoms after the reaction.

PMID- 10887324
TI  - Class I chitinases, the panallergens responsible for the latex-fruit syndrome,
      are induced by ethylene treatment and inactivated by heating.
AB  - BACKGROUND: Class I chitinases have been identified as the major panallergens in
      fruits associated with the latex-fruit syndrome, such as avocado, banana, and
      chestnut. However, other plant foods containing these enzymes have not been
      related to this syndrome. OBJECTIVE: We sought out class I chitinases in the
      green bean, a legume that is known to express chitinases but is not associated
      with latex allergy, and examined whether the content or allergenic activity of
      chitinases can be modified by physical or chemical treatments. METHODS: IgE
      binding proteins in untreated bean samples, as well as in ethylene- and heat
      treated samples, were detected by using a pool of sera from patients with latex
      fruit allergy. Putative allergens were purified by cation-exchange chromatography
      and characterized by N-terminal sequencing, enzymatic activity assays,
      immunodetection with sera and antichitinase antibodies, and immunoblot inhibition
      tests. Skin prick tests with untreated and heated purified allergens were also
      carried out. RESULTS: An IgE-binding protein of 32 kd that was also recognized by
      antichitinase antibodies was detected in green bean extracts. This reactive
      component was strongly induced by ethylene treatment. The protein, designated
      PvChI, was identified as a class I chitinase closely related to the major avocado
      allergen Prs a 1. Immunoblot inhibition assays demonstrated cross-reactivity
      between both allergens. Purified PvChI induced positive skin prick test responses
      in 7 of 8 patients with latex-fruit allergy. Heat treatment of both Prs a 1 and
      PvChI produced a full loss of their allergenic capacities both in vitro and in
      vivo. No IgE-binding component was detected in the white mature bean in which the
      main isolated 32-kd protein corresponded to a nonreactive phytohemagglutinin.
      CONCLUSIONS: Ethylene treatment induces the expression of plant class I
      chitinases. The allergenic activity of plant class I chitinases seems to be lost
      by heating. This fact could explain why plant foods containing these putative
      allergens that are consumed after cooking are not usually associated with the
      latex-fruit syndrome.

PMID- 10887325
TI  - Wasp or hippopotamus?

PMID- 10887326
TI  - Reanalysis of Blanc PD et al, "Use of herbal products, coffee or black tea, and
      over-the-counter medications as self treatments among adults with asthma".

PMID- 10887328
TI  - Regulation of nuclear factor of activated T-cell family transcription factors
      during T-cell development in the thymus.
AB  - BACKGROUND: T lymphocytes undergo a series of developmental events in the thymus,
      and signaling through the T-cell antigen receptor is crucial in this differential
      program. The nuclear factor of activated T cells (NFATs) may be involved in
      transcriptional induction of cytokine genes and other immunoregulatory genes in T
      cells. OBJECTIVES: We have examined the distribution of 3 NFAT family members
      (NFAT1, NFATc, and NFATx) in human fetal thymocytes, by using semiquantitative RT
      PCR and electrophoretic mobility shift assay. RESULTS: The messenger RNA of NFATx
      was expressed in all T-lymphocyte subsets tested, and expression was highest in
      CD4(+)CD8(+) thymocytes. Conversely, mRNA of NFAT1 was preferentially expressed
      in mature CD4(+) single-positive cells. NFATc mRNA was present at low levels in
      all subsets but was strongly induced by treatment with phorbol ester plus calcium
      ionophore. Using electrophoretic mobility shift assay, we observed stimulation
      dependent NFAT-DNA binding in CD4(+)CD8(+) thymocytes, which was largely
      dependent on NFATx protein. This DNA-binding activity was inhibited by
      cyclosporin A, which indicated that NFATx nuclear translocation in CD4(+)CD8(+)
      thymocytes was regulated by calcineurin phosphatase. In contrast, NFAT1 and NFATc
      (and to some extent NFATx) were responsible for NFAT DNA binding in the CD4(+)
      cells. CONCLUSIONS: Expression of NFAT family members is differentially regulated
      during T-cell development, and NFATx may be involved in T-cell antigen
      receptor/calcineurin-dependent signaling in CD4(+)CD8(+) thymocytes.

PMID- 10887329
TI  - Analysis of antiapoptosis activity of human GM-CSF receptor.
AB  - Human GM-CSF (hGM-CSF) induces proliferation and sustains the viability of a
      mouse IL-3-dependent lymphoid cell line BA/F3 that expresses the functional hGM
      CSF receptor (hGMR). To reveal an antiapoptotic mechanism of hGM-CSF, we analyzed
      various apoptotic markers of BA/F3 cells in various conditions. Within 24 hours
      of factor depletion, caspase 3-like, but not caspase 1-like, enzyme activity and
      DNA fragmentation were augmented. Analysis with the tyrosine kinase inhibitor
      (genistein) and an MEK1 inhibitor (PD98059) on antiapoptosis activity indicates
      that the activation of either the genistein-sensitive signaling pathway or the
      PD98059-sensitive signaling pathway of the betac subunit may be sufficient to
      suppress apoptosis through hGMR. Because hGMR mutants (which activate JAK2 but
      neither STAT5 nor the MAPK cascade) have antiapoptotic activity in BA/F3 cells,
      the involvement of JAK2, excluding the molecules mentioned earlier, for
      antiapoptosis activity seems likely. Because the JAK2 inhibitor AG-490 suppressed
      the antiapoptotic activity of hGM-CSF, the essential role for JAK2 activation to
      maintain the viability is considered. Interestingly, hGMR mutants, which lack
      MAPK cascade activation, require a higher dose of hGM-CSF than that for wild-type
      hGMR. Because the expression level and affinity to hGM-CSF among wild-type hGMR
      and mutant hGMR are the same, we speculated that biologic response is determined
      by a combination of strength of various signaling events.

PMID- 10887330
TI  - The fas antigen is involved in thymic T-cell development as a costimulatory
      molecule, but not in the deletion of neglected thymocytes.
AB  - To determine whether the Fas antigen (Fas) is involved in thymic T-cell
      development, we introduced the lymphoproliferation (lpr) mutation into a T-cell
      receptor-alphabeta transgenic mouse (DO10 mouse) and generated 4 genotypes of T
      cell receptor transgenic mice homozygous or heterozygous for the lpr mutation
      with selecting or nonselecting H-2 haplotype. Unexpectedly, we found that the
      homozygous Fas mutation (lpr/lpr) induced a marked reduction in CD4(+)CD8(+)
      double-positive (DP) thymocytes in mice with nonselecting background and that the
      thymus showed severe cortical atrophy. We also found that the homozygous Fas
      mutation inhibited the activation of DP thymocytes in the process of positive
      selection, as indicated by the lower levels of CD5 and CD69 expressions on DP
      thymocytes in lpr/lpr mice with both selecting and nonselecting background than
      those of lpr/+ mice. Furthermore, we found a significant skewing from CD4(+) to
      CD8(+) single-positive thymocytes in lpr/lpr mice with nonselecting background
      compared with that in the corresponding lpr/+ mice. Taken together, these results
      indicate that Fas is involved in thymic T-cell development, DP thymocyte
      generation and positive selection, as a costimulatory molecule but is not
      involved in the deletion of neglected thymocytes.

PMID- 10887331
TI  - Delayed recovery of CDR3 complexity of the T-cell receptor-beta chain in
      recipients of allogeneic bone marrow transplants who had virus-associated
      interstitial pneumonia: monitor of T-cell function by CDR3 spectratyping.
AB  - BACKGROUND: In the T-cell receptor (TCR)-beta chain, complementary-determining
      region 3 (CDR3) contains specific peptide sequences essential for recognition.
      Diversity of this region is considered to contribute to immunocompetence in
      humans. OBJECTIVE: The purpose of this study was to define the process of
      reconstitution of CDR3 complexity of the TCR-beta chain after allogeneic bone
      marrow transplantation and to investigate the association between host
      immunocompetence and CDR3 complexity. METHODS: Diversity of the CDR3 region of
      the TCR-beta chain was examined by CDR3 size distribution analysis with the use
      of an automated DNA sequencer. RESULTS: Reconstitution of the alphabeta T-cell
      repertoire and CDR3 diversity was incomplete for at least 2 months after bone
      marrow transplantation. Delayed reconstitution of T-cell diversity was more
      marked in immunocompromised hosts. Unlike the situation in patients who received
      allogeneic bone marrow grafts, the recovery of CDR3 complexity was almost perfect
      by 2 months after transplantation in patients who received allogeneic blood stem
      cells. Clonal expansion of alphabeta T cells after allogeneic bone marrow
      transplantation was readily detected by CDR3 size spectratyping analysis.
      CONCLUSION: PCR-based CDR3 size spectratyping may be a useful tool for clinically
      monitoring immune reconstitution after allogeneic bone marrow transplantation.

PMID- 10887332
TI  - Serum markers of graft-versus-host disease after bone marrow transplantation.
AB  - BACKGROUND: Graft-versus-host disease is one of the major complications after
      allogenic bone marrow transplantation, but it is not easy to anticipate the
      onset. OBJECTIVES: The purpose of this study was to determine clinically useful
      markers of acute graft-versus-host disease. METHODS: We measured the serum levels
      of tumor necrosis factor-alpha, soluble tumor necrosis factor receptor 1, soluble
      c-kit, soluble Fas, soluble intercellular adhesion molecule-1, growth-related
      oncogene protein-alpha, thrombomodurin, and interleukin-16 in 13 patients at 1 to
      7 weeks after allogenic bone marrow transplantation. RESULTS: The patients with
      acute graft-versus-host disease showed a significant increase of tumor necrosis
      factor, soluble tumor necrosis factor receptor 1, soluble Fas, soluble
      intercellular adhesion molecule-1, and growth-related oncogene protein-alpha,
      although there was a decrease of soluble c-kit. The increases of serum soluble
      tumor necrosis factor receptor 1, intercellular adhesion molecule-1, and growth
      related oncogene protein-alpha were preceded by the elevation of soluble Fas.
      CONCLUSION: The patients with acute graft-versus-host disease had increased serum
      levels of tumor necrosis factor-alpha, soluble tumor necrosis factor receptor 1,
      soluble Fas, and soluble intercellular adhesion molecule 1 and a decreased
      soluble c-kit level. Tumor necrosis factor-alpha and soluble c-kit were shown to
      be sensitive and specific parameters for graft-versus-host disease after bone
      marrow transplantation, and soluble Fas was shown to be a predictor of acute
      graft-versus-host disease after bone marrow transplantation.

PMID- 10887333
TI  - Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma in patients
      with acute graft-versus-host disease after allogeneic bone marrow
      transplantation.
AB  - BACKGROUND: Acute graft-versus-host disease still represents the major factor
      that limits successful allogeneic bone marrow transplantation. Cytokines released
      by type 1 T-helper cells are thought to play a pivotal role in acute graft-versus
      host disease. OBJECTIVE: This study was performed to investigate whether the
      serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma were
      associated with the manifestation of acute graft-versus-host disease. METHODS:
      Serum cytokine levels were measured by sandwich ELISA in 18 patients who
      underwent allogeneic bone marrow transplantation. RESULTS: Serum levels of
      soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma were increased in patients in
      whom acute graft-versus-host disease developed. However, only serum soluble IL-2
      receptor levels were significantly related to disease severity. Serum levels of
      IL-12 and IL-18, both of which are mainly produced by activated macrophages, were
      increased in different phases of acute graft-versus-host disease, especially
      grade I. Serum levels of soluble IL-2 receptor and IFN-gamma were significantly
      elevated in patients with fever. CONCLUSION: Serum levels of soluble IL-2
      receptor were more closely related to the severity of acute graft-versus-host
      disease than those of IL-12, IL-18, and IFN-gamma.

PMID- 10887334
TI  - Induction of autologous graft-versus-host disease with cyclosporin A after
      peripheral blood stem cell transplantation: analysis of factors affecting
      induction.
AB  - BACKGROUND: Induction of autologous graft-versus-host disease after peripheral
      blood stem cell transplantation has not been studied well. OBJECTIVE: The purpose
      of this study was to analyze the factors that affect the development of
      autologous graft-versus-host disease. METHODS: Nineteen patients with non
      Hodgkin's lymphoma underwent peripheral blood stem cell transplantation followed
      by the administration of cyclosporin A for 28 days (group A) or 21 days (group B)
      and IFN-gamma. RESULTS: Autologous graft-versus-host disease failed to develop in
      the any of the group A patients, who did not receive total body irradiation for
      conditioning and underwent the transplantation with unmanipulated peripheral
      blood stem cells, although cytotoxic activity against autologous lymphocytes was
      detectable in peripheral blood mononuclear cells obtained from all of them after
      the transplantation. Autologous graft-versus-host disease developed in 2 of 4
      patients in group A who received enriched CD34(+) cells and in 7 of 11 patients
      who underwent conditioning with total body irradiation. Maculopapular erythema
      that was compatible with graft-versus-host disease developed on days 19 to 27
      after the transplantation in these patients and resolved after 3 to 9 days
      without treatment. CONCLUSIONS: Either the depletion of regulatory cells from the
      graft by enrichment of CD34(+) cells or the abolition of the autoregulation by
      including total body irradiation in the conditioning regimen may be effective in
      inducing autologous graft-versus-host disease after peripheral blood stem cell
      transplantation. Three weeks of cyclosporin A therapy appears to be sufficient to
      induce autologous graft-versus-host disease in recipients of peripheral blood
      stem cells.

PMID- 10887336
TI  - Atopy and the human IL-4 receptor alpha chain.
AB  - BACKGROUND: Atopy is a common inherited disorder characterized by increased IgE
      responsiveness, but no functional analysis of the candidate genes related to
      atopy has been performed. IL-4 is important for B-cell production of IgE, and the
      human IL-4 receptor alpha chain (hIL-4Ralpha) is crucial for the binding and
      signal transduction of IL-4, so hIL-4Ralpha may be a candidate gene related to
      atopy. OBJECTIVE: We examined the relationship between the variation at amino
      acid 50 of hIL-4Ralpha and atopic asthma. METHODS: We performed a genetic study
      to investigate the relationship between the variation of amino acid 50
      (isoleucine [Ile(50)] or valine [Val(50)]) and atopic asthma in a Japanese
      population and a functional study with the use of transfectants that expressed
      hIL4Ralpha bearing either Ile(50) or Val(50). Furthermore, we analyzed CD23
      expression and IgE synthesis after IL-4 stimulation of peripheral blood
      mononuclear cells bearing either Ile(50) or Val(50). RESULTS: The prevalence of
      Ile(50) was higher than that of Val(50) in individuals with atopic asthma,
      especially during childhood. In transfectants, germline epsilon transcription
      activity and Stat6 activity were upregulated by the Ile(50) variant, compared
      with Val(50), but receptor affinity for IL-4 was similar between the two. CD23
      expression and IgE synthesis in response to IL-4 were augmented in Ile(50)
      expressing peripheral mononuclear blood cells compared to cells expressing
      Val(50). CONCLUSION: The Ile(50) variant of hIL-4Ralpha may be related to atopic
      asthma, particularly in children.

PMID- 10887335
TI  - Control of IL-5 production by human helper T cells as a treatment for
      eosinophilic inflammation: comparison of in vitro and in vivo effects between
      selective and nonselective cytokine synthesis inhibitors.
AB  - BACKGROUND: Helper T cells are involved in the pathophysiologic condition of
      asthma, so modulation of cytokine production may be effective therapy. OBJECTIVE:
      We aimed to selectively control the synthesis of IL-5 by helper T cells and
      tested in vivo effects using a murine asthma model. METHODS: The effect of
      dexamethasone, FK506, cyclosporin A, and nonactin (a macrolide compound produced
      by Streptomyces griseus) on cytokine production by allergen-specific T-cell
      clones was determined. The effect of these agents and an anti-IL-5 neutralizing
      antibody on airway eosinophilic inflammation was investigated in a murine asthma
      model. RESULTS: Dexamethasone, FK506, and cyclosporin A suppressed the production
      of IL-2, IL-4, and IL-5 by human helper T cells, which shows a similar
      concentration-response relationship in each case. Cyclosporin A and dexamethasone
      inhibited airway eosinophilia in vivo. Nonactin suppressed IL-5 synthesis but not
      IL-2 or IL-4 synthesis, and it also significantly suppressed airway eosinophilia.
      CONCLUSION: Nonactin only suppressed IL-5 synthesis and was as effective against
      eosinophilia as cyclosporin A and dexa-methasone, which indicates that IL-5 is a
      reasonable therapeutic target in allergic disorders that are accompanied by
      eosinophilic inflammation.

PMID- 10887337
TI  - Influence of IgE-mediated activation of cultured human mast cells on
      proliferation and type I collagen production by human dermal fibroblasts.
AB  - BACKGROUND: Mast cells have been suggested to be involved in fibrotic conditions,
      but it still remains unknown whether IgE-mediated activation of human mast cells
      promotes fibrogenesis by human fibroblasts. OBJECTIVE: The purpose of this study
      was to determine whether IgE-mediated activation of cultured human mast cells can
      promote fibrogenesis by cultured human dermal fibroblasts. METHODS: Mast cells
      derived from human umbilical cord blood cells were incubated with IgE and then
      activated by anti-IgE, and histamine release was measured. IgE-sensitized mast
      cells were cocultured with fibroblasts from normal dermis and activated with anti
      IgE to induce histamine release, after which proliferation and type I collagen
      synthesis by the fibroblasts were determined. RESULTS: Coculture of subconfluent
      human dermal fibroblasts with IgE-sensitized mast cells did not affect fibroblast
      proliferation. However, fibroblast proliferation was increased by activated mast
      cells, and a significant increase was observed in the presence of 10(5) or 3 x
      10(5) mast cells/mL. The promotion of fibroblast proliferation by mast cells (3 x
      10(5)/mL) was partly inhibited by ketotifen at a concentration that significantly
      reduced histamine release from mast cells. On the other hand, IgE-mediated
      activation of mast cells did not increase type I collagen production by confluent
      human dermal fibroblasts. CONCLUSION: IgE-mediated activation of cultured human
      mast cells could increase the proliferation of human dermal fibroblasts, but did
      not promote type I collagen production by the fibroblasts under the conditions
      tested.

PMID- 10887338
TI  - Effect of mast cell-derived mediators and mast cell-related neutral proteases on
      human dermal fibroblast proliferation and type I collagen production.
AB  - BACKGROUND: Possible involvement of mast cells in various fibrotic conditions has
      been suggested, but the relative contribution of each mast cell mediator and
      neutral protease to fibroproliferative activity remains to be elucidated.
      OBJECTIVE: We investigated the effect of mast cell-derived mediators and mast
      cell-related neutral proteases on type I collagen production and proliferation by
      human dermal fibroblasts. METHODS: Mast cell-derived mediators or neutral
      proteases were added to cultured fibroblasts from normal dermis, and cell
      proliferation and type I collagen synthesis were assayed. RESULTS: Fibroblast
      proliferation was increased by 2.8 x 10(-9) mol/L prostaglandin D(2) and 10
      microgram/mL carboxypeptidase A, but not by leukotriene D(4) or cathepsin G at
      the concentrations studied. Proliferation was increased by tryptase in a
      concentration-dependent manner, and a significant increase was observed at
      concentrations of 1 and 10 microgram/mL. Production of type I collagen by
      fibroblasts was increased in the presence of 2.0 x 10(-9) mol/L leukotriene D(4)
      and 10 microgram/mL tryptase. CONCLUSION: Mast cell-derived mediators
      prostaglandin D(2) and leukotriene D(4) and mast cell-related neutral proteases
      carboxypeptidase A and tryptase increase the proliferation and type I collagen
      production of human dermal fibroblasts in various manners.

PMID- 10887339
TI  - Production of fibrogenic cytokines by cord blood-derived cultured human mast
      cells.
AB  - BACKGROUND: Mast cells are a potential source of cytokines, but their
      contribution to nonallergic inflammatory conditions, such as fibrosis, remains
      unclear. OBJECTIVE: We investigated whether cord blood-derived cultured human
      mast cells could produce fibrogenic cytokines by IgE-mediated activation.
      METHODS: Mast cells were obtained from human cord blood mononuclear cells by
      culture with stem cell factor and IL-6. The mast cells were incubated with human
      myeloma IgE and were activated with anti-IgE. The expression of messenger RNA for
      fibrogenic cytokines was examined by the reverse-transcription polymerase chain
      reaction, and cytokine protein was assayed by enzyme-linked immunosorbent assay,
      or bioassay. RESULTS: Cultured human mast cells constitutively expressed mRNA for
      transforming growth factor-beta(1), and its expression was not increased by anti
      IgE stimulation. The cells released this factor into the culture medium
      spontaneously, which showed bioactivity after heat treatment. The mast cells also
      expressed mRNA for platelet-derived growth factor A, which was enhanced with a
      peak at 3 hours by stimulation with anti-IgE. Conditioned medium from
      nonactivated mast cells did not contain basic fibroblast growth factor, but this
      cytokine was released into the medium in a time-dependent manner after
      stimulation with anti-IgE. CONCLUSION: Human mast cells activated by IgE-mediated
      stimulation show production of fibrogenic cytokines that varies depending on the
      cytokine, which suggests possible involvement of mast cell cytokines in the
      development of fibrosis.

PMID- 10887340
TI  - Role of mast cells in the onset of IgE-mediated late-phase cutaneous response in
      mice.
AB  - BACKGROUND: In mice that are passively sensitized to IgE, cutaneous antigen
      challenge produces a biphasic response with peaks at 1 and 24 hours after
      challenge. OBJECTIVE: We investigated the role of mast cells in the IgE-mediated
      late-phase reaction in mice. METHODS: We histologically and ultrastructurally
      investigated the morphologic changes of mast cells during the biphasic responses.
      RESULTS: Degranulation of mast cells, which was observed between 4 and 24 hours
      after challenge, reached a peak at 8 hours. Piecemeal degranulation was seen
      during the immediate phase reaction. The number of IL-6-positive mast cells was
      increased after 4 hours in both IgE-sensitized and unsensitized mice, but
      positive cells showed a greater increase in sensitized mice and reached a peak
      after 8 hours. With in situ hybridization experiments, mast cells were positive
      for IL-6 messenger RNA at 6 hours after challenge. CONCLUSION: These findings
      indicate that anaphylactic degranulation of mast cells and the expression of IL-6
      mRNA within 4 hours after antigen challenge are important for the onset of the
      late-phase allergic cutaneous reaction in mice.

PMID- 10887341
TI  - Signaling through the beta2 integrin prolongs eosinophil survival.
AB  - BACKGROUND: Recently, adhesion molecules have been suggested to play an important
      role in allergic inflammatory diseases such as bronchial asthma. It is unclear
      whether eosinophil activation and paracrine or autocrine synthesis of
      eosinophilopoietic growth cytokines is mediated through signaling by
      intercellular adhesion molecule-1 (ICAM-1) and the beta2 integrin family.
      OBJECTIVE: We examined whether signaling by ICAM-1 and its ligands (beta2
      integrins) could prolong eosinophil survival. METHODS: Eosinophils were isolated
      from patients with hypereosinophilia by modified CD16 negative selection. After
      culture with or without recombinant soluble ICAM-1, eosinophil viability was
      measured by trypan blue dye exclusion. RESULTS: Eosinophil survival was prolonged
      in cultures with recombinant soluble ICAM-1 compared with cultures without it (P
      <.01 on days 2, 4, and 6); this effect was dose-dependent. Eosinophil survival in
      cultures with recombinant soluble ICAM-1 was significantly inhibited by
      antibodies against ICAM-1 (P <.01), complement receptor 3 (P <.01), and
      lymphocyte function-associated antigen-1beta (P <.01). Anti-IL-3 showed no effect
      on eosinophil survival, whereas anti-IL-5 caused partial inhibition of survival.
      Interestingly, anti-granulocyte/macrophage colony-stimulating factor caused the
      complete inhibition of eosinophil survival in cultures with recombinant soluble
      ICAM-1. CONCLUSION: These results suggested the importance of the beta2 integrins
      in eosinophil-mediated allergic inflammation.

PMID- 10887342
TI  - Beta-adrenergic agonists and bronchial hyperreactivity: role of beta2-adrenergic
      and tachykinin neurokinin-2 receptors.
AB  - BACKGROUND: beta(2)-Adrenergic agonists are the most widely used bronchodilators
      for the treatment of asthma. On the other hand, there is concern that excessive
      use of beta(2)-agonists may contribute to the exacerbation of asthma. However,
      the mechanism of such adverse effects of beta(2)-agonists is not completely
      clear. OBJECTIVE: The aim of this study was to assess the direct influence of
      beta(2)-agonists on airways by analyzing the effect of a beta(2)-agonist,
      fenoterol, on airway sensitivity in an animal model and on tachykinin neurokinin
      2 receptor expression in bovine tracheal smooth muscle. METHODS: We performed an
      acetylcholine challenge test on ovalbumin sensitized guinea pigs that were
      exposed to daily inhalation of ovalbumin and fenoterol. We also investigated the
      effects of fenoterol on neurokinin-2 receptor messenger RNA and density with
      Northern blot analysis and receptor binding assay. RESULT: The increase of airway
      responsiveness and the decrease of beta(2)-adrenergic receptors were found in
      guinea pigs that were treated with fenoterol. There were time- and dose-dependent
      increases of neurokinin-2 receptor mRNA and of density in tracheal smooth muscle
      that was treated with fenoterol. CONCLUSION: This increased airway
      responsiveness, increased neurokinin-2 receptor expression, and decreased beta(2)
      adrenergic receptor density may be relevant to asthma exacerbation.

PMID- 10887343
TI  - T-regulatory 1 cells: a novel subset of CD4 T cells with immunoregulatory
      properties.
AB  - Clonal deletion and clonal anergy are well established mechanisms of peripheral
      tolerance. A role has also been described for clonal suppression by regulatory
      cells in the induction of peripheral tolerance to a variety of antigens. However,
      it has been difficult to isolate regulatory cells and to define their mechanism
      of action. We have recently reported the in vitro generation and characterization
      of a novel subset of CD4(+) T cells that have regulatory properties and are able
      to suppress antigen-specific immune responses in vitro and in vivo. These T
      regulatory 1 (Tr1) cells are defined by their unique profile of cytokine
      production and make high levels of IL-10 and TGF-beta, but no IL-4 or IL-2. The
      IL-10 and TGF-beta produced by these cells mediate the inhibition of primary
      naive T cells in vitro. There is also evidence that Tr1 cells exist in vivo, and
      we have documented the presence of high IL-10-producing CD4(+) T cells in
      patients with severe combined immunodeficiency who have received allogeneic stem
      cell transplants. These findings support the notion that Tr1 cells are involved
      in the regulation of peripheral tolerance and that they could potentially be used
      as a cellular therapy to modulate immune responses in vivo.

PMID- 10887344
TI  - Natural killer 1.1(+) T cells and "natural suppressor" T cells in the bone
      marrow.
AB  - Unusual cells in the bone marrow of mice and/or humans suppress immune responses
      and inhibit the mixed leukocyte reaction, graft-versus-host disease, and systemic
      autoimmunity. Previous studies showed that these "natural suppressor" T cells
      expressed the CD4(-)CD8(-) T-cell receptor-alphabeta(+) phenotype. More recent
      studies demonstrate that the latter cells express the natural killer 1.1 (NK1.1)
      marker and are members of the NK1.1(+) T-cell family that secrete high levels of
      IFN-gamma and IL-4 after initial activation. The suppressive activity of the bone
      marrow NK1.1(+) T cells is dependent on their rapid secretion of high levels of
      IL-4. This unique cytokine secretion is not observed in conventional NK1. 1(-) T
      cells and can downregulate the function of the latter cells.

PMID- 10887345
TI  - Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Executive
      summary. Sinus and Allergy Health Partnership.

PMID- 10887346
TI  - Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Sinus and
      Allergy Health Partnership.

PMID- 10887347
TI  - Doppler-determined peak systolic tricuspid pressure gradient in persons with
      normal pulmonary function and tricuspid regurgitation.
AB  - The Doppler-estimated peak systolic tricuspid pressure gradient is the most
      reliable noninvasive method for the evaluation of pulmonary artery systolic
      pressure in patients with tricuspid regurgitation. Our goal was to evaluate the
      range of this gradient in healthy persons and determine a normal upper limit. We
      studied 53 healthy persons (34 women, 19 men; aged 14 to 55 years, mean 38.9 +/-
      12.7 years) who did not smoke and who had an adequate Doppler signal of tricuspid
      regurgitation. The presence of pulmonary or cardiac disorders was excluded by a
      review of the subject's medical history in addition to physical examination,
      spirometry, arterial blood gasses determination, electrocardiography, chest x-ray
      examination, and rest echocardiography. Tricuspid gradient ranged from 12.6 to
      29. 3 mm Hg (mean 19.3 +/- 4.0); 35.8% of patients had values higher than 20 mm
      Hg. In conclusion, a tricuspid gradient of 30 mm Hg may be considered as the
      upper normal limit. The different approaches for estimating mean right atrial
      pressure are also discussed.

PMID- 10887348
TI  - Improvement in right ventricular systolic function after surgical correction of
      isolated tricuspid regurgitation.
AB  - Chronic tricuspid regurgitation (TR) may lead to impairment in right ventricular
      (RV) function. Whether surgical correction results in restoration of normal RV
      geometry and function is unknown. The purpose of this study was to determine
      whether surgical correction of TR results in improved RV geometry and function.
      Measurements of RV areas were made from digitized 4-chamber echocardiographic
      views. Right ventricular end-diastolic volume (RVEDV), right ventricular end
      systolic volume (RVESV), and ejection fraction (EF) were calculated with the
      single-plane subtraction method. There was a significant decrease in RVEDV
      (109.06 +/- 12.45 versus 71.63 +/- 6. 83; P =.005) and RVESV (76.2 +/- 9.83
      versus 44.5 +/- 5.58; P =.002) and a significant increase in RVEF (0.30 +/- 0.05
      versus 0.38 +/- 0. 05; P =.01) at a mean follow-up of 130 +/- 63 days after
      surgery. These results demonstrate significant remodeling of the right ventricle
      with reduction in size and improved EF after tricuspid valve surgery.

PMID- 10887349
TI  - Right ventricular dysfunction after thrombolysis in patients with right
      ventricular infarction.
AB  - BACKGROUND: Right ventricular (RV) infarction is frequently associated with
      highest risk of death and major complications. Doppler echocardiography can be
      useful in the diagnosis of RV involvement. The goal of this study was to evaluate
      Doppler echocardiography features associated with RV involvement and a poor
      prognosis. METHODS: Two-dimensional Doppler echocardiography was performed before
      and after thrombolysis in 108 consecutive patients with an RV infarction. The
      bedside examination was performed before and 2 to 3 hours after thrombolytic
      therapy, and repeated after 1 and 7 days. All patients underwent coronary
      angiography after 20 days, and the perfusion of the coronary-related artery (>
      thrombolysis in myocardial infarction [TIMI] 3 grade) was evaluated. RESULTS:
      Patients were divided into 2 groups according to the recovery of global and
      regional RV function after thrombolytic therapy. In the group of patients who
      showed a normalization or improvement of RV wall motion (as assessed by RV wall
      motion score index), we found a TIMI grade III perfusion in 78% of patients. The
      analysis of interatrial septal motion and interventricular septal motion showed a
      normalization in all reperfused patients. Major complication and deaths were more
      frequent in patients with echocardiographic findings of RV dysfunction persisting
      after thrombolytic therapy. CONCLUSION: In patients with RV infarction treated
      with thrombolysis, persistent RV dysfunction is associated with a higher risk for
      the development of major cardiac complications and death.

PMID- 10887350
TI  - Left atrial appendage function in patients with cardioembolic stroke in sinus
      rhythm and atrial fibrillation.
AB  - The purpose of this study was to determine the left atrial appendage (LAA)
      function in patients with stroke. The study group consisted of 61 patients with
      stroke and 37 control subjects. Patients with stroke were divided into 2 groups
      on the basis of the presence of atrial fibrillation (group 1) or sinus rhythm
      (group 2). Group 1 showed a significant reduction of LAA flow velocities (13.2 +/
      6.4 cm/s versus 27.5 +/- 8 cm/s, P <.05) and significant increase in LAA areas
      (minimum area: 360.5 +/- 204 mm(2) versus 217.7 +/- 113.9 mm(2), P =.004). Group
      2 showed a decrease in LAA flow velocities (17.7 +/- 8.2 cm/s versus 27.5 +/- 8
      cm/s, P <.05), but no significant change was found in LAA areas. No significant
      difference was found in other parameters related to LAA. These findings show that
      a decreased LAA flow velocity is a risk factor for stroke in patients in sinus
      rhythm without LAA enlargement. Left atrial appendage area was increased in size
      only in patients with atrial fibrillation.

PMID- 10887351
TI  - Integrated backscatter assessment of left atrial spontaneous echo contrast in
      chronic nonvalvular atrial fibrillation: relation with clinical and
      echocardiographic parameters.
AB  - Integrated backscatter (IB) provides the quantitative assessment of left atrial
      spontaneous echo contrast (SEC). The IB intensity of the left atrial cavity
      relative to the left ventricular cavity is related to atrial thrombus in patients
      with atrial fibrillation (AF) or sinus rhythm. However, little is known about the
      relation between the quantitative SEC value of the left atrial cavity and
      variables implying thromboembolism in nonvalvular AF. To examine this relation,
      we performed transesophageal echo-cardiography with IB analysis in 65 patients
      with chronic nonvalvular AF. The quantitative SEC value of the left atrial cavity
      was defined as the difference between atrial IB intensity and ventricular IB
      intensity (corrected IB intensity). The corrected IB intensity was correlated
      with the left atrial dimension (r = 0.25, P =.049), the left atrial appendage
      velocity (r = -0.41, P <.001), and the duration of AF (r = 0.23, P =. 023). The
      corrected IB intensity was higher in patients who had a history of hypertension
      (3.2 +/- 2.2 dB versus 2.0 +/- 1.6 dB, P =. 018), SEC (3.9 +/- 1.9 dB versus 1.4
      +/- 1.1 dB, P =.002), and left atrial thrombus (4.5 +/- 2.7 dB versus 2.2 +/- 1.7
      dB, P <.001) when compared with those who did not have these abnormalities. The
      corrected IB intensity was significantly lower in patients with significant
      mitral regurgitation than in those without it (1.1 +/- 1. 2 dB versus 2.7 +/- 2.0
      dB, P =.036). When the cutoff value of the corrected IB intensity was set at
      >/=2.0 dB, the sensitivity for left atrial thrombus was 78% and the specificity
      was 55%. In patients with chronic nonvalvular AF, the quantitative SEC value of
      the left atrial cavity depends on the duration of AF as well as the left atrial
      dimension and appendage velocity. Although IB may be capable of identifying
      patients with higher risk of cardiogenic embolism, a large-scale prospective
      study is needed to actually establish this.

PMID- 10887352
TI  - Personal ultrasound imager: abdominal aortic aneurysm screening.
AB  - BACKGROUND: Miniaturized ultrasonographic machines (2.5-MHz curved-array
      transducer connected to a compact 2.6-kg console), termed personal ultrasound
      imagers (PUIs), may enable detection of occult abdominal aortic aneurysms (AAAs).
      OBJECTIVES: Our goals were to determine whether a PUI is capable of screening for
      AAAs and to compare the results with an established screening examination with
      standard echocardiography (SE). METHODS: One hundred twenty-five patients (aged
      >70 years) with hypertension who were referred for transthoracic echocardiography
      were enrolled. After SE, a focused screening with a PUI examination was performed
      by a blinded sonographer. An AAA was defined as a focal enlargement of the aorta
      >30 mm. Results and the length of time to image the aorta were compared for both
      tests. RESULTS: We studied 64 men and 61 women (aged 76.8 +/- 5 years; mean blood
      pressures: systolic 145.7 +/- 18 and diastolic 78.6 +/- 10; body surface area 1.9
      +/- 0.2 m(2)). The mean time for SE was 2.9 +/- 1.5 minutes and for the PUI
      examination was 4.6 +/- 2.3 minutes. By using SE as the gold standard, the
      sensitivity and specificity of the PUI were 91% and 96%, respectively. The
      positive predictive value of the PUI was 71%, and the negative predictive value
      was 99%. CONCLUSION: A PUI can be used to screen for occult AAAs as an extension
      of the physical examination. Results are comparable to an established screening
      strategy that uses more expensive, nonportable echocardiographic equipment.

PMID- 10887353
TI  - Tissue harmonic imaging: a new method for predicting left ventricular thrombus?
AB  - We report a case of spontaneous echocardiographic contrast in the left ventricle
      visualized by transthoracic second harmonic imaging, but not by fundamental
      imaging, and subsequent thrombus formation.

PMID- 10887354
TI  - Transthoracic echocardiographic demonstration of massive pulmonary thrombus
      caused by protein C deficiency.
AB  - Few cases of pulmonary embolism detected by transthoracic echocardiography (TTE)
      have been reported. We present a case of a patient affected by pulmonary embolism
      caused by protein C deficiency. Transthoracic echocardiography showed a thrombus
      in transit (ie, visualization of a thrombus within the pulmonary artery). A
      hypercoagulable state caused by deficiency of protein C is a rare cause of
      pulmonary thromboembolism. Our experience demonstrates a massive pulmonary
      thrombus resulting from such a deficiency. Transthoracic echocardiography should
      be considered as the first diagnostic method for patients with suspected
      pulmonary embolism.

PMID- 10887355
TI  - Intermittent electromechanical dissociation as an unusual sign of prosthetic
      valve thrombosis in a patient with prosthetic fibrous ingrowth.
AB  - We describe the echocardiographic features of an unusual hemodynamic phenomenon
      of intermittent electromechanical dissociation during regular sinus tachycardia
      in a patient with prosthetic mitral valve thrombosis. Thrombolysis with a
      solution of recombinant tissue-type plasminogen activator resulted in the
      disappearance of electromechanical dissociation and was effective in stabilizing
      the patient's condition. The later discovery of panus covering the valve ring
      after the lysis of clots confirmed surgery as the definitive treatment.

PMID- 10887356
TI  - Loffler's syndrome: pulmonary vein and transmitral doppler flow analysis by
      transesophageal echocardiography-report of a case.
AB  - Loffler's syndrome is defined by prolonged and profound eosinophilia and
      restrictive cardiomyopathy. Doppler echocardiography is useful in both the
      diagnosis and management of this entity. On the other hand, diastolic dysfunction
      is assessed better by transesophageal echocardiography than by transthoracic
      echocardiography, mainly in the analysis of pulmonary vein Doppler flow. We
      describe a patient with Loffler's syndrome, whose pulmonary vein flow, obtained
      by transesophageal echocardiography, was helpful for better management of the
      disease.

PMID- 10887357
TI  - An unusual case of acquired ventricular septal defect as a complication of aortic
      valve endocarditis: echocardiographic delineation of multiple subvalvular
      complications in one patient.
AB  - We describe a patient with unusual echocardiographic features of prosthetic
      aortic valve endocarditis. Transesophageal echocardiography in this patient
      demonstrated a large multiloculated aortic root abscess extending to mitral
      aortic intervalvular fibrosa, a high acquired ventricular septal defect,
      paravalvular aortic regurgitation caused by aortic valve dehiscence, and anterior
      mitral valve leaflet perforation.

PMID- 10887358
TI  - Transesophageal echocardiography assessment of severe ostial left main coronary
      stenosis.
AB  - Doppler echocardiography is commonly used in the assessment of stenotic valvular
      orifices. We describe the application of transesophageal echocardiography for the
      detection of a critical ostial left main coronary stenosis. Because preoperative
      coronary angiography often is not routinely performed in young patients
      undergoing valve surgery, application of Doppler echocardiography can potentially
      prevent catastrophic complications, particularly in atypical cases.

PMID- 10887359
TI  - Long-axis contraction of the ventricles: a modern approach, but described already
      by Leonardo da Vinci.

PMID- 10887360
TI  - Echocardiographic features of genetic diseases: part 7. Complex genetic
      disorders.

PMID- 10887361
TI  - Quantitative study of myocardial microcirculation in arterial hypertension due to
      progressive inhibition of NO synthesis.
AB  - OBJECTIVE: To study the quantitative changes in intramyocardial blood vessels in
      rats in whom nitric oxide synthesis was inhibited. METHODS: Four groups of 10
      rats were studied: control (C25 and C40) and L-NAME (L25 and L40). The animals
      L25 and L40 received L-NAME in the dosage of 50mg/kg/day for 25 and 40 days,
      respectively. On days 26 and 41 the animals in groups 25 and 40 were sacrificed.
      Analysis of the myocardium was performed using light microscopy and stereology.
      RESULTS: Arterial blood pressure and heart weight increased 74.5 and 57.8% after
      25 days and 90.2 and 34.6% after 40 days, respectively. Comparing the L-NAME rats
      with the respective controls revealed that vessel volume density decreased 31.3%
      after 40 days, and the vessel length-density decreased 53.5% after 25 days and
      25.7% after 40 days. The mean cross-sectional area of the vessels showed an
      important reduction of 154.6% after 25 days. The intramyocardial vessels
      decreased significantly in length-density in the L-NAME animals. The mean cross
      sectional area of the vessels, which normally increases during heart growth
      between 25 and 40 days, showed a precocious increase by the 25th day in the L
      NAME rats. This suggests an increase of the size of the heart, including blood
      vessels. CONCLUSION: The inhibition of the NO synthesis provokes rarefaction in
      the intramyocardial vessels that progresses with the time of administration of L
      NAME.

PMID- 10887362
TI  - Immediate and long term evolution of valve replacement in children less than 12
      years old.
AB  - OBJECTIVE: The aim of this work was the follow-up and evaluation of valve
      replacement in children under 12 years of age. METHODS: Forty-four children less
      than 12 years old were underwent valve replacement at INCOR-HCFMUSP between
      January 1986 and December 1992. Forty (91%) were rheumatic, 39 (88.7%) were in
      functional classes II or IV, 19 (43.2%) were operated upon on an emergency basis,
      and 6 (13.6%) had atrial fibrillation. Biological prostheses (BP) were employed
      in 26 patients (59.1%), and mechanical prostheses (MP) in 18 (40.9%). Mitral
      valves were replaced in 30 (68.7%), aortic valves in 8 (18.2%), a tricuspid valve
      in 1 (2.3%), and double (aortic and mitral) valves in 5 (11.4) of the patients.
      RESULTS: Hospital mortality was of 4.5% (2 cases). The mean follow-up period was
      5.8 years. Re-operations occurred in 63.3% of the patients with BP and in 12.5%
      of those with MP (p=0.002). Infectious endocarditis was present in 26.3% of the
      BP, but in none of the cases of MP (p=0.049). Thrombosis occurred in 2 (12.5%)
      and hemorrhage in one (6.5%) of the patients with a MP. Delayed mortality
      occurred in 5 (11.9%) of the patients over a mean period of 2.6 years; four had
      had BP and one had a MP (NS). Actuarial survival and re-operation-free curves
      after 10 years were respectively, 82.5+/-7.7 (SD)% and 20.6+/-15.9%. CONCLUSION:
      Patients with MP required fewer re-operation, had less infectious endocarditis
      and lower late mortality rates compared with patients with bioprostheses. The
      former, therefore, appear to be the best valve replacement for pediatric
      patients.

PMID- 10887363
TI  - Holt-Oram syndrome revisited. Two patients in the same family.
AB  - Holt-Oram syndrome was first described in 1960 as an association of familial
      heart disease and musculoskeletal abnormalities. The most important findings
      include atrial septal defects, atrioventricular conduction abnormalities,
      vascular hypoplasia, and upper limb musculoskeletal deformities. We report two
      patients with this syndrome in the same family and discuss the variability of the
      musculoskeletal abnormalities and their association with the cardiac morphologic
      defects. Both patients in this study had associated eosinophilia, which has not
      been reported in the literature.

PMID- 10887364
TI  - Pompe's disease or type IIa glycogenosis.
AB  - This is the report of a five-month-old child presenting clinical evidence of
      Pompe's disease: severe hypotonicity, hyporeflexia and congestive heart failure.
      The ECG showed a short PR interval, the chest radiography disclosed marked
      cardiomegaly, and the echocardiogram revealed marked left ventricular hypertrophy
      - the most typical finding of this disease. A skeletal muscle biopsy led to final
      diagnosis, because in the histopathologic study marked increased glycogen
      accumulation was evident. Death occurred two months after symptom onset.

PMID- 10887365
TI  - Double outlet right ventricle with anterior and left-sided aorta and subpulmonary
      ventricular septal defect.
AB  - Double outlet right ventricle (DORV) is a heterogeneous group of abnormal
      ventriculoarterial connections where, by definition, both great arteries
      (pulmonary artery and aorta) arise primarily from the morphologically right
      ventricle. This condition affects 1-1.5% of the patients with congenital heart
      diseases, with a frequency of 1 in each 10,000 live births. We report the case of
      an 18-day-old infant with DORV and extremely rare anatomical features, such as
      anterior and left-sided aorta and subpulmonary ventricular septal defect (VSD).
      In addition to the anatomic features, the role of the echocardiogram for guiding
      the diagnosis and the surgical therapy of this congenital heart disease are
      discussed.

PMID- 10887366
TI  - Prevention of acute coronary events through the Mediterranean diet.

PMID- 10887367
TI  - Infectious agents in coronary atherosclerosis.

PMID- 10887368
TI  - Inoculation of Lacazia loboi into the subcutaneous tissue of the hamster cheek
      pouch.
AB  - The subcutaneous tissue of the hamster cheek pouch, a site of immunologic
      privilege, has been used to investigate the potential infectivity of different
      types of parasites. It has been demonstrated that the implantation of fragments
      of lesions induced by the fungus Lacazia loboi, the etiologic agent of Jorge
      Lobo's disease, into the subcutaneous tissue of the hamster cheek pouch resulted
      in parasite multiplication and dissemination to satellite lymph nodes16. Here we
      describe the evolution of lesions induced by the inoculation of the isolated
      fungus into this immunologically privileged site. The morphology of the
      inflammatory response and fungal viability and proliferation were evaluated.
      Inoculation of the fungus into the cheek pouch induced histiocytic granulomas
      with rare lymphocytes. Although fungal cells were detected for a period of up to
      180 days in these lesions, the fungi lost viability after the first day of
      inoculation. In contrast, when the parasite was inoculated into the footpad, non
      organized histiocytic lesions were observed. Langhan's giant cells, lymphocytes
      and fungal particles were observed in these lesions. Fungal viability was
      observed up to 60 days after inoculation and non-viable parasites were present in
      the persistent lesions up to 180 days post-inoculation. These data indicate that
      the subcutaneous tissue of the hamster cheek pouch is not a suitable site for the
      proliferation of Lacazia loboi when the fungus isolated from human tissues is
      tested.

PMID- 10887369
TI  - Three year seroepidemiological study of varicella-zoster virus in Sao Paulo,
      Brazil.
AB  - A serosurvey of varicella has been carried out in children attending the public
      school network of Sao Paulo city, Brazil, from 1992 to 1994. This study was
      performed in order to establish the age related prevalence of antibodies against
      varicella-zoster virus (VZV) and its age specific transmission dynamics pattern
      in these children. Among 2500 schools in the city of Sao Paulo public network,
      304 were randomly selected; 7 children of a given age (ranging from 1 to 15
      years) were randomly selected in each school, and blood samples were obtained by
      fingerprick into filter paper. Blood eluates were analyzed for the presence of
      antibodies to VZV by ELISA. Proportion of seropositivity were calculated for each
      age group. Samples consisted of 1768 individuals in 1992, 1758 in 1993, and 1817
      in 1994, resulting in 5343 eluates. A high proportion of seropositive children
      from 1 to 3 years of age was observed, ascending until 10 years of age and
      reaching a plateau around 90% afterwards. VZV transmission in this community was
      similar along the three years of the study. In children attending public schools
      in the city of Sao Paulo, contact with VZV occurs in early childhood. If
      immunization against VZV is considered it should be introduced as soon as
      possible.

PMID- 10887370
TI  - Congenital cytomegalovirus infection in a neonatal intensive care unit in brazil
      evaluated by PCR and association with perinatal aspects.
AB  - Cytomegalovirus (CMV) infection is the most common congenital infection,
      affecting 0.4% to 2.3% newborns. Most of them are asymptomatic at birth, but
      later 10% develop handicaps, mainly neurological disturbances. Our aim was to
      determine the prevalence of CMV shed in urine of newborns from a neonatal
      intensive care unit using the polymerase chain reaction (PCR) and correlate
      positive cases to some perinatal aspects. Urine samples obtained at first week of
      life were processed according to a PCR protocol. Perinatal data were collected
      retrospectively from medical records. Twenty of the 292 cases (6.8%) were CMV-DNA
      positive. There was no statistical difference between newborns with and without
      CMV congenital infection concerning birth weight (p=0.11), gestational age
      (p=0.11), Apgar scores in the first and fifth minutes of life (p=0.99 and 0. 16),
      mother's age (p=0.67) and gestational history. Moreover, CMV congenital infection
      was neither related to gender (p=0.55) nor to low weight (<2,500 g) at birth
      (p=0.13). This high prevalence of CMV congenital infection (6.8%) could be due to
      the high sensitivity of PCR technique, the low socioeconomic level of studied
      population or the severe clinical status of these newborns.

PMID- 10887371
TI  - Thiamphenicol in the treatment of chancroid. A study of 1,128 cases.
AB  - Thiamphenicol, an aminic derivate of hydrocarbilsulfonil propandiol, was used for
      the treatment of 1,171 chancroid bearing patients. Each patient was medicated
      with 5.0 g of granulated thiamphenicol, orally, in a single dose, and was
      reevaluated 3, 7 and 10 days after the treatment. Ten patients (0.89%) did not
      respond to the proposed treatment. 133 patients presented healed ulcers after 3
      days of treatment, 976 patients healed chancres on the seventh day after the
      treatment, and 39 patients took 10 days to present healed chancres. The results
      of this study indicate that the rate of patients that were cured, the low
      incidence of side effects, and the practicality of administration make of
      thiamphenicol an excellent choice for the treatment of chancroid.

PMID- 10887372
TI  - Susceptibility of clinical isolates of Bacteroides fragilis group strains to
      cefoxitin, cefoperazone and ticarcillin/clavulanate.
AB  - A total of 40 strains of the B. fragilis group was isolated from clinical
      specimens in two hospital centers in Fortaleza from 1993 to 1997. The most
      frequently isolated species was Bacteroides fragilis (19 strains) and most
      isolates came from intra-abdominal and wound infections. The susceptibility
      profile was traced for cefoxitin, cefoperazone and ticarcillin-clavulanate by
      using the agar dilution reference method. All isolates were susceptible to
      ticarcillin-clavulanate (128/2 microg/ml). Resistance rates of 15 and 70% were
      detected to cefoxitin (64 microg/ml) and cefoperazone (64 microg/ml),
      respectively. Such regional results permit a better orientation in choosing this
      group of antibiotics for prophylaxis and therapy especially in relation to
      cefoxitin, which is frequently used in the hospital centers studied.

PMID- 10887373
TI  - Toxoplasma encephalitis in AIDS patients in Sao Paulo during 1988 and 1991. A
      comparative retrospective analysis.
AB  - We conducted a retrospective analysis of Toxoplasma encephalitis patients from
      Instituto de Infectologia Emilio Ribas, the main AIDS hospital of Sao Paulo,
      Brazil, during two different stages of the HIV epidemics, in 1988 (38 patients)
      and 1991 (33 patients). There were AIDS-related demographic differences, but the
      clinical presentation and diagnostic efficiency were similar, usually based on
      tomography and clinical response to therapy, with a clear distinction from other
      CNS infections, based on clinical and laboratory findings. Specific serologic
      studies were performed less often in 1991, with a high frequency of therapy
      change. The direct acute death rate from Toxoplasma encephalitis was high during
      both periods, i.e. 8/38 in 1988 and 10/33 in 1991. The direct acute death rate
      for the patients from the two periods as a whole was 25.4% (18/71), related to
      the time of HIV infection, absence of fever and presence of meningeal irritation
      at presentation, blood leukocytes higher than 10,000/mm3 and blood lymphocytes
      lower than 350/mm3. Toxoplasma encephalitis is a preventable disease when
      adequate prophylactic therapy is used and is relatively easy to treat in
      diagnosed HIV patients. Unfortunately, this severe and deadly disorder is the HIV
      diagnostic disease in several patients, and our data support the need for careful
      management of these patients, especially in those countries with a high
      toxoplasmosis prevalence where AIDS is concurrent with economic and public health
      problems.

PMID- 10887374
TI  - A clinical, epidemological, laboratorial, histological and ultrasonographical
      evaluation of anti-HCV EIA-2 positive blood donors.
AB  - Between 1992 and 1997, 790 blood donors with anti-HCV EIA-2 strongly reagent
      (relationship between the sample optical density/cut-off > 3) detected at the
      blood bank serological screening, were evaluated in ambulatory environment. They
      were all negative for Chagas disease, syphilis, hepatitis B (HBsAg) and AIDS.
      Blood samples were collected at the first ambulatorial evaluation, for hemogram,
      biochemical tests and new serological tests for HCV (anti-HCV EIA-2). In blood
      samples of 226 repeatedly reagent anti-HCV EIA-2 blood donors, supplementary
      "immunoblot" test for HCV (RIBA-2) was used. In 209 donors, the presence of HCV
      RNA was investigated by the PCR test. The abdominal ultrasonography was realized
      in 366 donors. In 269 patients liver biopsy was performed for the
      histopathological study. The follow-up of blood donors showed that 95.6% were
      repeatedly EIA-2 reagent, 94% were symptomless and denied any hepatitis history,
      with only 2% mentioning previous jaundice. In 47% of this population at least one
      risk factor has been detected for the HCV transmission, the use of intravenous
      drugs being the main one (27.8%). Blood transfusion was the second factor for HCV
      transmission (27.2%). Hepatomegaly was detected in 54% of the cases. Splenomegaly
      and signs of portal hypertension have seldom been found in the physical
      examination, indicating a low degree of hepatic compromising in HCV. Abdominal
      ultrasound showed alterations in 65% of the subjects, being the steatosis the
      most frequent (50%). In 83. 5% of the donors submitted to the liver biopsy, the
      histopathological exam showed the presence of chronic hepatitis, usually
      classified as active (89%) with mild or moderate grade in most of the cases
      (99.5%). The histopathological exam of the liver was normal in 1.5% of blood
      donors. The RIBA-2 test and the HCV-RNA investigation by PCR were positive in
      respectively 91.6 and 75% of the anti-HCV EIA-2 reagent donors. The HCV-RNA
      research was positive in 82% of the RIBA-2 positive subjects, in 37.5% of the
      indeterminate RIBA-2 donors and in 9% of the negative RIBA-2 donors. Chronic
      hepatitis has also been observed in 50% of the histopathological exams of the
      anti-HCV EIA-2 reagent donors which were indeterminate RIBA-2. Among 18 blood
      donors with minimal changes histopathological exam 11 (61%) were HCV-RNA
      positive. Our blood donors anti-HCV reagent generally had clinical, laboratorial
      and histopathological features observed in patients with chronic HCV hepatitis
      and a high proportion could be identified in interviews and medical evaluation
      realized in blood blanks. Generally, these HCV infected donors are identified and
      discharged only by the serological tests results.

PMID- 10887375
TI  - Evaluation of standard reagents for radial-immunodiffusion assays. In vitro
      control of rabies vaccines.
AB  - The RID assay is one of the in vitro methods used for in-process control in the
      production of rabies vaccines for veterinary use. It has been shown to be very
      useful for determining antigen concentration in the final bulk product. The work
      presented in this paper, including the production and standardization of
      candidate standard reagents for use in the Radial Immunodiffusion Assay (RID) was
      carried out at the Pan American Institute for Food Protection and Zoonoses
      (INPPAZ/PAHO/WHO). The study was completed with the cooperation of the Faculty of
      Veterinary Sciences, National University of La Plata (NULP), Argentina, where the
      validation of the proposed standards and the quality control of samples from 28
      different batches of rabies vaccines produced with Pasteur strain rabies virus
      (PV) in BHK cells were performed. The activity of the vaccines was determined by
      in vivo (NIH) and in vitro (RID)assays. The results of the candidate reagents for
      the reagent standardization tests showed stability, sensitivity and
      reproducibility. The Relative Potency the 1.2 between the problem vaccines and
      the reference vaccine was estimated by variance and regression analysis. The
      results of our validation study show that the INPPAZ (PAHO/WHO) is capable of
      producing and distributing the above-mentioned standard reagents, as well as of
      providing support for the incorporation of the RID technique (sensitive, rapid
      and inexpensive) to the laboratories that manufacture rabies vaccines in Latin
      America and the Caribbean.

PMID- 10887376
TI  - Persistent infections in chronic Chagas' disease patients treated with anti
      Trypanosoma cruzi nitroderivatives.
AB  - We used a molecular method and demonstrated that treatment of the chronic human
      Trypanosoma cruzi infections with nitroderivatives did not lead to
      parasitological cure. Seventeen treated and 17 untreated chronic Chagas' disease
      patients, with at least two out of three positive serologic assays for the
      infection, and 17 control subjects formed the study groups. PCR assays with
      nested sets of T. cruzi DNA primers monitored the efficacy of treatment. The
      amplification products were hybridized to their complementary internal sequences.
      Untreated and treated Chagas' disease patients yielded PCR amplification products
      with T. cruzi nuclear DNA primers. Competitive PCR was conducted to determine the
      quantity of parasites in the blood and revealed < 1 to 75 T. cruzi/ml in
      untreated (means 25.83+/-26.32) and < 1 to 36 T. cruzi/ml in treated (means
      6.45+/-9.28) Chagas' disease patients. The difference between the means was not
      statistically significant. These findings reveal a need for precise definition of
      the role of treatment of chronic Chagas' disease patients with nitrofuran and
      nitroimidazole compounds.

PMID- 10887377
TI  - Hepatitis C virus in monozygotic twins.
AB  - A case of a pregnant patient with chronic hepatitis C who gave birth to
      monozygotic twins that were infected with HCV is reported. One of the newborns
      was positive for HCV-RNA in blood sample collected 12 hours after delivery. The
      other newborn was negative for HCV-RNA at birth, but was detected HCV viremia at
      three months of age. The results have led to the conclusion that one of the twins
      was probably contaminated in the intrauterine period, while the other acquired
      the infection in the perinatal period. Both were negative for HCV-RNA and for
      anti-HCV in the serum samples collected at nine months of age. The report
      describes the changes in the laboratory tests conducted in mother and twins until
      29 months after delivery.

PMID- 10887378
TI  - Gallium-67 imaging in a patient with paracoccidioidomycosis: a case report.
AB  - A 26 year-old female was admitted with abdominal pain, fever and weight loss. The
      clinical and laboratory investigations led to the diagnosis of
      paracoccidioidomycosis. Gallium-67 whole body images correlated well with the
      clinical course of the disease and with the patient's prognosis.

PMID- 10887379
TI  - Is demodex really non-pathogenic?
AB  - Although usually considered a non-pathogenic parasite in parasitological
      textbooks, Demodex folliculorum has been implicated as a causative agent for some
      dermatological conditions, such as rosacea-like eruptions and some types of
      blepharitis. Several anecdotal reports have demonstrated unequivocal tissue
      damage directly related to the presence of the parasite. However, this seems to
      be exceedingly rare, in contrast with the marked prevalence of this infestation.
      We have had the opportunity to observe one of such cases. A 38-year-old woman
      presented with rosacea-like papular lesions in her right cheek. Histopathological
      examination revealed granulomatous dermal inflammation with a well-preserved mite
      phagocytized by a multinucleated giant cell. This finding may be taken as an
      evidence for the pathogenicity of the parasite, inasmuch as it does not explain
      how such a common parasite is able to produce such a rare disease.

PMID- 10887381
TI  - Environmental tobacco smoke exposure among non-smoking waiters: measurement of
      expired carbon monoxide levels.

PMID- 10887380
TI  - Production of monoclonal antibodies anti-Taenia crassiceps cysticerci with cross
      reactivity with Taenia solium antigens.
AB  - We describe the production of the potential monoclonal antibodies (MoAbs) using
      BALB/c mice immunized with vesicular fluid (VF)-Tcra (T. crassiceps) antigen.
      Immune sera presented anti-VF-Tcra (<20kD) IgG and IgM antibodies with cross
      reactivity with T. solium (Tso) antigen (8-12, 14, and 18 kD). After cell fusion,
      we selected 33 anti-Tcra and anti-Tso reactive IgM-clones and 53 anti-Tcra
      specific IgG-clones, 5 of them also recognizing Tso antigens. Two clones
      identified the 8-14 and 18kD peptides of VF-Tcra.

PMID- 10887382
TI  - Prognosis related to staging systems for chronic lymphocytic leukemia.
AB  - CONTEXT: Chronic lymphocytic leukemia (CLL) is a clonal lymphoproliferative
      disorder, characterized by B lymphocytic proliferation. CLL is the most frequent
      adult leukemia in Western countries, accounting for 25 to 30% of all white
      leukemic patients. OBJECTIVE: To evaluate clinical and staging characteristics in
      prognosis of chronic lymphocytic leukemia. DESIGN: Evaluation of clinical-staging
      data. SETTING: Universidade Federal de Sao Paulo - Escola Paulista de Medicina /
      Universidade de Alfenas. SAMPLE: 73 patients diagnosed from 1977 to 1994. MAIN
      MEASUREMENTS: Sex, ethnic origin, age, lymphadenopathy, splenomegaly,
      hepatomegaly, three or more areas of lymphoid enlargement, hemoglobin (g/dl),
      lymphocytes/mm3, Platelets/mm3 RESULTS: Mean survival of patients was 76 months,
      median age was 65 years, ranging from 33 to 87. Forty-four patients (60.3%) were
      male and 29 (39.7%) female. CONCLUSION: The Binet system determined a better
      prognosis than Rai.

PMID- 10887383
TI  - Environmental tobacco smoke exposure among non-smoking waiters: measurement of
      expired carbon monoxide levels.
AB  - CONTEXT: Exposure to environmental tobacco smoke is a health risk that is of
      concern to patrons and of particular concern to employees of restaurants and
      bars. OBJECTIVE: To assess environmental tobacco smoke exposure (using expired
      carbon monoxide levels) in non-smoking waiters before and after a normal day's
      shift and to compare pre-exposure levels with non-smoking medical students.
      DESIGN: An observational study. SETTING: Restaurants with more than 50 tables or
      100 places in Sao Paulo. SUBJECTS: 100 non-smoking restaurant waiters and 100 non
      smoking medical students in Sao Paulo, Brazil. MAIN MEASUREMENTS: Levels of
      expired carbon monoxide, measured with a Smokerlyser (Bedfont EC 50 Scientific),
      before and after a normal day's work. RESULTS: Waiters' pre-exposure expired
      carbon monoxide levels were similar to those of medical students, but after a
      mean of 9 hours exposure in the workplace, median levels more than doubled (2.0
      ppm vs. 5.0 ppm, P <0.001). Post-exposure carbon monoxide levels were correlated
      with the number of tables available for smokers (Kendall's tau = 0.2, P <0.0001).
      CONCLUSIONS: Exposure to environmental tobacco smoke is the most likely
      explanation for the increase in carbon monoxide levels among these non-smoking
      waiters. These findings can be used to inform the ongoing public health debate on
      passive smoking.

PMID- 10887384
TI  - Increased exhalation of hydrogen peroxide in healthy subjects following cigarette
      consumption.
AB  - CONTEXT: Increased hydrogen peroxide has been described in the expired breath
      condensate (H2O2-E) of several lung conditions, such as acute respiratory
      distress syndrome, chronic obstructive pulmonary disease and asthma. This
      technique has been advocated as being a simple method for documenting airway
      inflammation. OBJECTIVE: To evaluate H2O2-E in healthy cigarette smokers, and to
      determine the acute effects of the consumption of one cigarette on H2O2-E levels.
      TYPE OF STUDY: Prospective, controlled trial. SETTING: A pulmonary function
      laboratory in a University Hospital. PARTICIPANTS: Two groups of healthy
      volunteers: individuals who had never smoked (NS; n=10; 4 men; age = 30.6 +/- 6.2
      years) and current cigarette smokers (S; n=12; 7 men; age = 38.7 +/- 9.8). None
      of the volunteers had respiratory symptoms and all showed normal spirometric
      tests. INTERVENTION: Expired air was collected from all volunteers through a face
      mask and a plastic collecting system leading into a flask with dry ice and pure
      ethanol. Samples from the group S were collected twice, before and half an hour
      after the combustion of one cigarette. MAIN MEASUREMENTS: Expired hydrogen
      peroxide using the Gallati and Pracht method. RESULTS: The S and NS groups showed
      comparable levels of H2O2-E at basal conditions [NS = 0.74 microM (DP 0.24) vs. S
      = 0.75 microM (DP 0.31)]. The smokers showed a significant increase in H2O2-E
      levels half an hour after the consumption of only one cigarette [0.75 microM (DP
      0.31) vs. 0. 95 microM (DP 0.22)]. CONCLUSION: The present results are consistent
      with the concept that smokers increase oxidative stress with elevated production
      of reactive oxygen species, contributing to the development of smoking-related
      disorders.

PMID- 10887385
TI  - Antidepressant efficacy of sertraline and imipramine for the treatment of major
      depression in elderly outpatients.
AB  - CONTEXT: Most double-blind studies of efficacy and tolerability of sertraline as
      compared to tricyclics in the treatment of late-life major depression have used
      amitriptyline as a standard, leading to the inevitable conclusion that the former
      drug is better tolerated than the latter, with both being equally efficacious.
      OBJECTIVE: To compare the antidepressant efficacy and tolerability of sertraline
      (50 mg/day) and imipramine (150 mg/day) in the first 6 weeks of the treatment of
      major depression in the elderly. DESIGN: A randomized double-blind parallel study
      with 6 weeks of follow-up. SETTING: The psychogeriatric clinic at the Institute
      of Psychiatry, Hospital das Clinicas, Faculty of Medicine of the University of
      Sao Paulo. PARTICIPANTS: 55 severe and moderately depressed non-demented
      outpatients aged 60 years or more. INTERVENTION: Patients were assigned to
      sertraline 50 mg/day or imipramine 150 mg/day. MAIN MEASUREMENTS: CAMDEX
      interview. Psychiatric diagnosis followed the guidelines for "Major Depressive
      Episode" according to DSM-IV criteria. Severity of symptoms was evaluated using
      the "CGI" and "MADRS" scales. Cognitive state was assessed using the Mini-Mental
      State Examination. Side effects were assessed using the "Safetee-Up" schedule.
      RESULTS: Both groups had a significant decrease in depressive symptoms according
      to the MADRS scores after 6 weeks of treatment (P = 0.01). No significant
      differences between groups were detected regarding treatment outcome (t = 0.4; P
      = 0.7). Although the dropout rate was greater in the imipramine group, the
      overall tolerability among patients who completed the 6-week trial was similar in
      both test groups. CONCLUSIONS: Both sertraline and imipramine exhibited good
      efficacy and an acceptable side-effect profile for elderly depressed patients
      after 6 weeks of antidepressant treatment.

PMID- 10887386
TI  - Incidence of Gardnerella vaginalis, Candida sp and human papilloma virus in
      cytological smears.
AB  - CONTEXT: In spite of the wide-ranging literature on the microbiology of normal
      and abnormal flora of the vagina, there are few studies on the relationship
      between human papilloma virus (HPV) and other vaginal microorganisms. OBJECTIVE:
      To analyze the frequency of infection by human papilloma virus (HPV) and other
      agents like Candida sp., Gardnerella vaginalis and Trichomonas vaginalis in
      cytological smears. DESIGN STUDY: Retrospective study SETTING: A public tertiary
      referral center. SAMPLE: An analysis of 17,391 cytologies from outpatients seen
      between January 1997 and August 1998. The control group was made up of patients
      in the same age group and same period with no cytological evidence of HPV
      infection. Patients with a diagnosis of cervical intraepithelial neoplasia (CIN)
      II or III were excluded from this analysis. MAIN MEASUREMENTS: The diagnosis of
      HPV infection was made in accordance with the criteria of Schneider et al. and
      the diagnosis of Gardnerella vaginalis was made with a finding of clue cells.
      RESULTS: 390 (2. 24%) had alterations consistent with infection by HPV, sometimes
      associated with CIN I. The results showed that Gardnerella vaginalis was the most
      frequent agent in women with HPV infection (23.6% versus 17.4%; P <0.05), while
      in the control group the most frequent agent was Candida sp. (23.9% versus 13.8%;
      p <0.001). CONCLUSION: In spite of this study being based solely on cytological
      criteria, in which specific HPV and Gardnerella diagnostic tests were not used,
      the cytological smear is widely used in clinical practice and the data presented
      in this investigation show that there is an association between Gardnerella
      vaginalis and HPV infection. It remains to be established whether the
      microorganisms favor each other.

PMID- 10887387
TI  - Efficacy in treatment of subclinical cervical HPV infection without
      intraepithelial neoplasia: systematic review.
AB  - CONTEXT: The treatment of the subclinical Human papillomavirus (HPV) infection of
      the uterine cervix is controversial. OBJECTIVE: To assess the efficacy of any
      therapy for subclinical HPV infection of the cervix without intraepithelial
      neoplasia, via a search in the medical literature. METHOD: We performed a
      systematic review with a comprehensive reference search in Medline, LILACS,
      Excerpta Medica, AIDSLINE, Popline, Cochrane Library and other authors' reference
      lists to identify experimental studies of therapy for subclinical HPV infection
      without intraepithelial neoplasia of the uterine cervix. In order to identify
      unpublished studies, we also contacted experts in the area, clinical trial
      registries, pharmaceutical industries, government and research institutions. We
      also searched on the Internet and in the book-of-abstracts of some medical
      conferences. The studies identified were masked and selected by inclusion
      criteria to help ascertain their internal validity. The data about regression or
      progression of HPV infection were extracted from the studies included. RESULTS:
      We identified 67 studies related to the treatment of subclinical HPV infection
      without intraepithelial neoplasia of the uterine cervix. Only five clinical
      trials matched the inclusion criteria and none demonstrated significant
      differences between the experimental group and the control group concerning
      regression of HPV infection (with or without CIN I) or progression to higher
      grades of CIN. CONCLUSION: The evidence we found in the medical literature
      regarding the efficacy of any therapy for subclinical HPV infection without
      intraepithelial neoplasia of the uterine cervix was unsatisfactory.

PMID- 10887388
TI  - Duodenal damage complicating percutaneous access to kidney.
AB  - CONTEXT: Since the first percutaneous nephrostomy performed by Goodwin in 1954,
      technical advances in accessing the kidneys via percutaneous puncture have
      increased the use of this procedure and thus the complications too. Among these
      complications, digestive tract damage is not common. DESIGN: Case report. CASE
      REPORT: We report a duodenal lesion that was corrected using surgical exploration
      and we touch on the therapeutic options, which may be conservative or
      interventionist. We chose conservative treatment, which has been approached in
      diverse manners in the literature.

PMID- 10887390
TI  - Prostate Cancer: Detection and Management.

PMID- 10887389
TI  - Frontal sinus adenocarcinoma.
AB  - CONTEXT: Paranasal sinus cancer is considered rare, with an incidence of less
      than 1 per 100,000 per year, with the frontal sinus being the primary site in
      only 0.3%. We report a case of adenocarcinoma arising in the frontal sinus.
      DESIGN: Case report. CASE REPORT: A 59-year-old woman, secretary, came in
      February 1998 with a 4-month history of low intensity frontal headache. She
      denied contact with wood dust. On examination a non-tender swelling was noted
      over her right forehead next to the medial aspect of the right orbit. CT scan
      showed a soft-tissue mass involving frontal sinus with intracranial invasion
      through the posterior wall. The anterior ethmoid sinus and the medial aspect of
      the right orbit were also involved. MRI demonstrated dural thickening in
      communication with the frontal mass. She underwent an en-bloc tumor resection by
      craniotomy including orbital clearance. Histology revealed an adenocarcinoma.
      After surgery she had tumor recurrence, and chemotherapy and radiotherapy were
      started resulting in partial improvement.

PMID- 10887391
TI  - Screening for Prostate Cancer: Pros, Cons, and Reality.
AB  - Prostate cancer has become the most common cancer in men in the United States.
      The increasing prevalence of prostate cancer can be attributed to a number of
      causes, including relatively new detection modalities, the increasing life span
      of American men, and increased public awareness of the disease. The increased
      awareness has resulted from information in the lay press, recognition of
      prominent public figures who are living with or have died from prostate cancer,
      and an increasingly informed American public.

PMID- 10887392
TI  - The Need for and Difficulties With Establishing Guidelines for Prostate Cancer
      Treatment.
AB  - The best method for treating prostate malignancy is unknown. Significant
      geographical variations exist in the treatment recommendations for prostate
      cancer. Practice variation often indicates uncertainty regarding outcomes of
      intervention and signals the need for practice guidelines. Prostate cancer needs
      these guidelines, and efforts are currently underway to produce a practice policy
      document. The mechanisms of writing and implementing guideline documents are
      still evolving and are currently untested. Although significant benefits may be
      attributed to well-written and balanced practice policies, inappropriately
      restrictive guidelines are potentially harmful. The degree of flexibility within
      guideline policies needs careful consideration.

PMID- 10887393
TI  - Pathology in Prostate Cancer: Limitations With Current Techniques.
AB  - Study of the pathology of prostate cancer is the clinical mainstay for evaluating
      the biology of the disease to predict prognosis and to recommend treatment
      options. Recent studies of whole-mount specimens are beginning to clarify the
      significance of tumor volume, grade, and multifocality. The studies are limited,
      however, by the constraints imposed by our inability to perform repeated studies
      over time.

PMID- 10887395
TI  - Prostate Cancer: A View From the Other Side of the Fence.

PMID- 10887394
TI  - Hormonal Therapy for Prostate Cancer: When to Use It.
AB  - Androgen deprivation has been the standard treatment for advanced prostate
      cancer. With the development of antiandrogen drugs, combination hormonal therapy
      achieving "total androgen blockade" has been demonstrated to be superior to
      monotherapy for patients with low-tumor-burden metastatic disease. Combination
      therapy is now being used more aggressively in locally advanced disease, with
      phase II studies suggesting benefit as measured by prolonged disease-free
      survival. Phase III randomized, controlled trials currently are being conducted.

PMID- 10887396
TI  - Quality-of-Life Issues Associated With the Treatment of Prostate Cancer.
AB  - The incidence of prostate cancer in the United States has dramatically increased
      over the last several years. As a result of prostate-specific antigen testing,
      many more men have localized, asymptomatic prostate cancer at the time of initial
      diagnosis. Treatment options for patients with prostate-confined adenocarcinoma
      of the prostate include observation, radical prostatectomy, external beam
      radiotherapy, radioactive prostate implantation, hormonal therapy, cryotherapy,
      and various combinations of the above modalities. Quality of life can be affected
      by the tumor and by any of the hormonal, surgical, or radiotherapeutic
      interventions. These treatments raise complex and multidimensional issues.
      Although quality-of-life issues are becoming integral and important components of
      clinical research in prostate cancer, many challenges in research and practice
      remain.

PMID- 10887397
TI  - Commercial Oncology and Health Care Reform.

PMID- 10887399
TI  - Paclitaxel: Infusion Duration Effect on Toxicity and Efficacy.

PMID- 10887398
TI  - Ascites, Omental Metastases, and Inguinal Hernia with Tumor.

PMID- 10887400
TI  - The Role of Diagnostic Molecular Pathology in Detection of Minimal Residual
      Disease.

PMID- 10887401
TI  - Demographic Imperative.
AB  - That we live in an aging world is now well recognized. The steady, sustained
      growth of elderly populations is posing a considerable challenge to policymakers
      and after the turn of the century the numbers and proportions of elderly will
      rise rapidly in most developed and many developing countries. The increased
      numbers of the oldest members of the elderly population will generate special
      concerns. The well-documented survival advantage of women over men may be
      tempered by the suggestion that men spend a greater portion of life in an active,
      nondisabled state than women. Cross-national demographic and epidemiologic data
      may be used for defining and sharpening national policies that address aging
      populations.

PMID- 10887402
TI  - Cancer Incidence and Mortality in the Elderly: Profile of the Italian Problem.
AB  - In Italy, 28% of all deaths are due to cancer. Of the 15% of the population that
      is 65 years or older, 65% of cancer deaths occur in men and 69.5% in women. The
      proportional mortality and incidence of cancer in Italy varies with increasing
      age. All patients over 65 years are found to be at increased risk for intestinal
      cancers. In older men, the proportion of lung and urinary tract cancers
      decreases, while prostate, intestinal and gastric cancers increases. Prostate
      cancer predominates in men over 85 years and intestinal and gastric cancers are
      relatively more common than lung cancer. In women over age 74, intestinal cancer
      is most common. Breast, genital and lung cancers decrease rapidly with age, while
      stomach, liver, gallbladder and pancreatic cancers increase with age. The ratio
      of incidence to mortality for all cancers studied is shown to equalize with
      increased age, the probable result of lower hospitalization rates and less
      adequate cancer therapy for the elderly.

PMID- 10887403
TI  - Age-Related Clinical Trials of CALGB.
AB  - Women over 65 years are underrepresented in Cancer and Leukemia Group B (CALGB)
      breast cancer trials of adjuvant chemotherapy. There is greater participation in
      older patients with metastatic breast cancer except when toxic regimens are
      involved. Studies of stage III and IV Hodgkin's disease have shown that patients
      over 60 years achieved lower response rates, more leucopenia and
      thrombocytopenia, the shortest median time to recurrence, and the shortest median
      survival time. In acute myeloid leukemia a series of trials confirmed the
      disparity between young patients and those over 60 years whose complete response
      rate seldom exceeds 50%. In an effort to reduce toxicity rather than enhance the
      cure rate, CALGB showed that administration of GM-CSF after intensive induction
      chemotherapy was of no benefit in patients over 60 years. The use of G-CSF in
      acute lymphoblastic leukemia reduced hematologic toxicity and improved clinical
      outcome.

PMID- 10887404
TI  - Age and Gynecologic Cancer: The Gynecologic Oncology Group Experience.

PMID- 10887405
TI  - Management of Acute Myeloid Leukemia in the Elderly.
AB  - Studies evaluating chemotherapeutic treatment of acute myeloid leukemia in the
      elderly indicate that intensive therapy is required to induce durable responses.
      By providing full supportive measures, approximately 50% of patients go into
      complete remission and approximately 25% of responders will have durable complete
      remissions.

PMID- 10887406
TI  - Clinical Trials in Older Patients With Intermediate and High-Grade Lymphomas.
AB  - The number of studies concerning non-Hodgkin's lymphoma (NHL) in elderly patients
      has increased in the last few years. However, the effectiveness of treatments
      specifically devised for elderly patients with aggressive lymphoma must be
      determined despite a trend towards reduction of treatment-related death. Direct
      comparison of trial results is difficult since different age limits were set for
      the inclusion of patients on study, but we can confirm that the complete response
      rate decreases with increasing age. Comparison of results even among trials
      conducted on patients of the same age remains difficult due to the lack of
      homogeneity in prognostic factors related to the NHL as well as to associated
      comorbidity, mental status, physical activity and family and social status.

PMID- 10887407
TI  - Therapeutic Approaches to Invasive Bladder Cancer in the Elderly Patient.
AB  - Invasive transitional cell carcinoma (TCC) of the bladder is a potentially life
      threatening problem. Radical cystectomy and full-dose radiation therapy have been
      the standard approaches to controlling local disease and, in some cases, may be
      curative. However, 60% or more of treated patients die of metastatic disease.
      Newer approaches using active chemotherapeutic drug combinations, both before and
      after primary local therapy, may downstage local tumors but have not yet been
      demonstrated to increase the overall survival rate. Choice of combined modality
      therapy should take into consideration the primary tumor stage, potential
      treatment-related toxicities and morbidities, the patient's functional status,
      present and past medical problems, and treatment preference, but not age alone.

PMID- 10887408
TI  - Adjuvant Treatment of Colorectal Cancer in the Elderly.
AB  - From March 1992 until January 1994, 1,014 patients radically resected for Dukes'
      B(2), B(3) or C colon cancer were randomized to receive FU plus levamisole or FU
      plus leucovorin (LV) plus levamisole. Only 41% of patients older than age 70
      years, as compared to 53% of those younger, have completed the treatment as
      planned. This poorer compliance was not associated with a higher incidence or
      degree of toxicity. Only a small difference in percentages was detected between
      the age groups of patients requiring dose reductions or treatment delays, while
      the percentages of patients that had their treatment discontinued was markedly
      increased in the older age group, without a parallel increase in severe toxicity.
      Preliminary results suggest that adjuvant chemotherapy with FU plus levamisole or
      FU plus LV plus levamisole is well tolerated by elderly patients and is not
      associated with greater toxicity in patients over 70 years of age than in younger
      patients. The lower adherence to the treatment plans in older patients may be due
      to reluctance by physicians and families to administer chemotherapy due to the
      misconception that the elderly are more prone to adverse reactions.

PMID- 10887409
TI  - Breast Cancer in the Elderly: Treatment of Metastatic Disease.
AB  - Metastatic breast cancer in the elderly is an incurable chronic disease.
      Comorbidity affects outcome significantly and is evaluated before treatments. A
      variety of treatment approaches are available, including medication, hormones,
      and cytotoxic chemotherapy, that can provide significant palliation.

PMID- 10887411
TI  - Priorities in Geriatric Oncology - Conference Summary.

PMID- 10887410
TI  - Caring for the Older Cancer Patient: Comprehensive Geriatric Evaluation.
AB  - Elderly patients comprise almost half of daily adult oncology practice, but
      management guidelines based on data from clinical trials performed in the elderly
      are lacking. Comprehensive geriatric evaluation and the use of different outcome
      measures for trials of interventions in the elderly are needed to provide
      clinicians and patients the information required to make the best management
      decisions.

PMID- 10887424
TI  - Drugs for rheumatoid arthritis.

PMID- 10887425
TI  - DLTBGYD.

PMID- 10887426
TI  - An unresponsive patient with a history of stroke.

PMID- 10887427
TI  - Abnormal ECG after extensive maxillofacial surgery.

PMID- 10887428
TI  - Improving management of type 2 diabetes mellitus: 2. Biguanides.

PMID- 10887429
TI  - WONCA: family doctors for the world.

PMID- 10887430
TI  - Cough, weakness, and dark urine.

PMID- 10887431
TI  - The prospects for gene therapy.

PMID- 10887433
TI  - Curable conspicuous ascites: the forgotten four.

PMID- 10887432
TI  - Managing painful diabetic neuropathy.

PMID- 10887434
TI  - Cancer chemoprevention: present status, future expectations.

PMID- 10887435
TI  - Skin rash, fever, and malaise in a young man.

PMID- 10887436
TI  - Oral antibiotics: are the old still gold?
AB  - Most common infections in ambulatory care can be treated effectively and safely
      with conventional antibiotics. A rational approach using such antibiotics as
      primary choices and reserving newer antibiotics for selected, more difficult-to
      treat infections will result in substantial cost savings and may help to prevent
      the rapid development of drug resistance.

PMID- 10887437
TI  - Abdominal pain in a woman with cancer.

PMID- 10887438
TI  - Must dementia remain a silent epidemic?

PMID- 10887439
TI  - The patient who had nothing to say.

PMID- 10887440
TI  - Progressive vision loss after pneumonia.

PMID- 10887441
TI  - Seven (plus one) secrets of a successful medical practice. Details make the
      difference on the business side.

PMID- 10887443
TI  - Get in with the e-crowd. E-mail can serve your practice if kept in check.

PMID- 10887442
TI  - More about pleural effusions.

PMID- 10887444
TI  - Osteoporosis prevention, detection, and treatment. A mandate for primary care
      physicians.
AB  - Prevention of bone loss through healthy lifestyle choices offers the greatest
      promise of minimizing fracture incidence. Safe, effective therapeutic options are
      available when drug therapy is prudent. Newer bisphosphonates, selective estrogen
      receptor modulators, and HRT delivery systems will soon be available to offer an
      even larger menu of choices for osteoporosis prevention and treatment. By
      implementing appropriate treatment, we can prevent bone loss, reduce fracture
      incidence, and improve function and quality of life, even in patients who have
      previously experienced fractures.

PMID- 10887445
TI  - The columnar-lined (Barrett's) esophagus. Can progression to cancer be prevented?
AB  - The risk of adenocarcinoma in patients with columnar-lined, or Barrett's,
      esophagus has risen dramatically in recent decades. In this article, Dr Stollman
      explains the difficulties in defining the condition and examines current
      strategies in prevention and management.

PMID- 10887446
TI  - Oral antidiabetic agents safe with renal disease?

PMID- 10887447
TI  - Treating the patient with multiple cosmetic product allergies. A problem-oriented
      approach to sensitive skin.
AB  - Treating patients with multiple allergies to cosmetic products is a difficult
      proposition. Many of these patients may simply be experiencing irritant contact
      dermatitis. Others may have defective barrier function caused by a dermatitis
      that requires treatment. And some patients with sensitive skin need to exercise
      care in choosing which products they use on their skin. For many of these
      patients, products with the fewest ingredients work best because they contain the
      least or no sensitizers, irritants, or cutaneous sensory stimulants.

PMID- 10887448
TI  - Alopecia areata. A clinical overview.
AB  - Alopecia areata is a common disorder usually diagnosed on the basis of history
      and physical findings alone. Although most patients have a good prognosis and can
      be successfully treated with available medications, treatment can be slow and
      emotionally difficult. Early recognition, intervention involving topical and/or
      intralesional therapy, and education can provide patients with comforting
      reassurance about eventual recovery.

PMID- 10887449
TI  - Hirsutism in women. Effective therapy that is safe for long-term use.
AB  - Hirsutism should be considered part of the androgen-excess syndrome unless
      another cause (e.g., masculinizing tumor, androgenic-drug use) can be
      established. Medical evaluation for transient or late-onset androgen excess,
      polycystic ovary syndrome, and insulin resistance is important because of the
      risks associated with chronic androgen excess. Treatment of insulin resistance
      with antiandrogen and/or insulin-lowering therapy can reduce ovarian testosterone
      levels and hirsutism. Simple laboratory evaluation (i.e., measuring total and
      free testosterone, DHEAS, and androstenedione) identifies about half of patients
      with hyperandrogenism. More extensive evaluation and testing are required in the
      remaining half. Combination therapies, specifically oral contraceptives along
      with antiandrogen agents, are the most effective. Studies suggest that addition
      of low-dose GnRH agonist therapy prolongs remission of hirsutism. Most methods
      produce improvement within 6 months, with continued improvement at 12 months.
      Successful treatment results in finer hair, decreased rate of growth, decreased
      need for cosmetic camouflage or removal, and improved appearance. All methods,
      whether used continuously or intermittently, should be considered long term.

PMID- 10887450
TI  - Acute and chronic herpes zoster. An ancient scourge yields to timely therapy.
AB  - With the US population aging steadily, herpes zoster represents a growing
      contributor to diminished quality of life. Dermatologic manifestations appear as
      immunity declines with age but rarely pose a significant threat, except in
      instances when ocular structures are involved. Pain is of more concern, because
      it usually accompanies and may even precede and persist after acute eruptions. In
      most young patients, pain is transient and bearable. Unfortunately, in the
      elderly--who are at highest risk for herpes zoster--pain is often more prolonged
      and more intense. In spite of a wide spectrum of interventions, palliative
      efforts remain rather ineffectual. At present, intervening as early as possible,
      ideally within 48 to 72 hours of disease onset, offers the greatest chance of
      minimizing neurologic sequelae. Inoculation with varicella vaccine in patients
      between ages 55 and 65 may prove to boost cell-mediated immunity sufficiently so
      that recrudescence of the varicella virus can be relegated to the annals of
      history.

PMID- 10887451
TI  - Hypertrophic cardiomyopathy. Tools for identifying risk and alleviating symptoms.
AB  - Hypertrophic cardiomyopathy is characterized by left or right ventricular
      hypertrophy that is usually asymmetric and involves the interventricular septum.
      The condition has numerous genetic, anatomic, and clinical variations and
      continues to stimulate interest and investigation into causes and treatment
      options. New genetic forms of the disorder are being identified because of the
      rapid growth of molecular genetics. However, even with technological advances and
      a large database of information, risk stratification and treatment of
      hypertrophic cardiomyopathy remain difficult and controversial. Because of the
      high risk of sudden death, it is imperative that patients be advised against
      participation in competitive sports.

PMID- 10887452
TI  - Problems in interpreting laboratory tests. What do unexpected results mean?
AB  - It is always important that physicians not overreact to apparently abnormal
      laboratory values by undertaking inappropriate further investigations or clinical
      treatments. When confronted with unexpected differing test results from repeat
      testing in the same individual, physicians should be aware of explanations other
      than laboratory error and change in the patient's clinical status. While test
      related variables may be factors, intraindividual biologic variation is much more
      common and may be the explanation for discrepant results. For this reason,
      physicians need to know which laboratory tests are associated with significant
      intraindividual biologic variation as well as the magnitude of possible changes.
      Age-associated physiologic changes may significantly alter certain laboratory
      values in the elderly without constituting a pathologic process. Laboratory
      values that may appear abnormal in 10% or more of the healthy elderly without
      necessarily representing a pathologic process include serum alkaline phosphatase,
      fasting blood glucose, 2-hour postprandial glucose, erythrocyte sedimentation
      rate, hemoglobin, and a normal serum creatinine level in the face of a markedly
      decreased creatinine clearance. To ensure proper assessment of the geriatic
      patient, the clinician needs to be aware of these age-related changes and
      possible effects on laboratory values. More clinical research is needed to
      establish appropriate reference ranges, especially for those over the age of 75
      years.

PMID- 10887453
TI  - Galactorrhea may be clue to serious problems. Patients deserve a thorough workup.
AB  - Three cases of nonphysiologic hyperprolactinemia associated with pituitary
      disease evidenced by galactorrhea are presented. Two patients had significant
      pituitary disease associated with low-level prolactin elevations. The third
      patient had only a history of infertility and expressible galactorrhea on
      examination. This patient was found to have high prolactin levels and a locally
      invasive pituitary tumor. Physicians need to be aware of the serious conditions
      associated with galactorrhea so that appropriate diagnostic studies can be done
      and treatment instituted.

PMID- 10887454
TI  - Infectious mononucleosis. Complexities of a common syndrome.
AB  - Infectious mononucleosis is common in adolescents and young adults. Although the
      syndrome is most often associated with Epstein-Barr virus, several other
      organisms can also cause infectious mononucleosis. Diagnosis is based on clinical
      findings and the presence of heterophil antibodies and atypical lymphocytes.
      Diagnosis may be more difficult in older adults because the presenting symptoms
      often differ from those seen in children. Symptoms usually resolve in 2 to 3
      weeks. Treatment of uncomplicated infectious mononucleosis is supportive, but
      corticosteroids may be beneficial for the treatment of several complications
      associated with Epstein-Barr virus. Physically active patients should be
      counseled about the risks of splenic injury.

PMID- 10887455
TI  - Two different lesions, same reason. Fixed drug eruption.

PMID- 10887456
TI  - Skin cancer.

PMID- 10887457
TI  - Surveillance for the impact in the UK of HIV epidemics in South Asia.
AB  - OBJECTIVES: To determine whether, because of the extensive recent spread of HIV
      infection in South Asia, South Asians (those people who classify themselves as
      Indian, Pakistani, Bangladeshi or Sri Lankan in origin) resident in the UK were
      at increased risk of HIV infection and to review current surveillance systems for
      detecting any such increase. DESIGN: Analysis of: ethnic grouping and probable
      country of infection recorded on voluntary confidential reports of AIDS cases and
      newly diagnosed HIV infections; blood donation testing data; reports of imported
      gonorrhoea infections; country of birth data from the unlinked anonymous (UA)
      survey of Sexually Transmitted Disease (STD) clinic attenders; district of
      residence data from the UA survey of pregnant women; ethnic grouping of prevalent
      diagnosed HIV infections. RESULTS: Few reported AIDS cases or HIV infections were
      found in people of South Asian ethnic origin and few reported HIV or gonorrhoea
      infections were associated with exposure in South Asia. Data derived from the UA
      programme suggested as yet no increase in HIV prevalence in either STD clinic
      attenders born in South Asia or in pregnant women resident in districts
      containing substantial numbers of ethnic South Asians. CONCLUSIONS: There was no
      evidence that South Asians resident in the UK are currently at greater risk of
      HIV infection than people of white ethnicity or, therefore, that south Asian
      heterosexuals are a group deserving priority in HIV prevention. However, as rapid
      spread of HIV infection is being recorded in the Indian subcontinent, continuous
      monitoring is necessary. This will be facilitated by improved collection of
      ethnic group information in all surveillance activities.

PMID- 10887458
TI  - Complaints and complications in pregnancy: a study of ethnic Norwegian and ethnic
      Pakistani women in Oslo.
AB  - OBJECTIVES: To describe the pattern of complaints and complications in pregnancy
      among ethnic Norwegian and ethnic Pakistani women in Oslo in order to modify
      antenatal care services. DESIGN: A cross-sectional study of hospital patients
      conducted in community hospitals in Oslo, Norway. A total of 137 obstetrical
      patients, 66 ethnic Pakistani and 71 ethnic Norwegian women were included in the
      study. Medical complications and subjective reported physical complaints during
      pregnancy were the main outcome measures. RESULTS: Among the ethnic Pakistani
      women complications were more common and the risks were higher for gestational
      diabetes [crude odds ratio (OR) = 5.6, 95% confidence interval (CI) = 1.5-20.5),
      intrauterine growth retardation (crude OR = 5.0, 95% CI = 1.4-18.8), hyperemesis
      gravidarum (crude OR = 3.7, 95% CI = 1.1-12.2) and anaemia (crude OR = 10.2, 95%
      CI = 3.3-31.4). The frequency of congenital malformations (p = 0.048, OR not
      calculated) were also higher. Among the ethnic Norwegian women the frequency of
      subjective reported physical complaints were more common and the risks were
      higher for pelvic girdle pain (crude OR = 0.4, 95% CI = 0.2-0.8) and exhaustion
      (crude OR = 0.2, 95% CI = 0.04-0.1). Infections such as hepatitis and
      tuberculosis only occurred in the Pakistani study group. CONCLUSION: This study
      indicates that health personnel delivering antenatal care to women of Pakistani
      origin need to be watchful for the following conditions: gestational diabetes,
      hyperemesis gravidarum, early diagnosis of the type of anaemia, fetal
      malformations and infections like hepatitis and tuberculosis. In addition, a
      correct diagnosis of intrauterine growth retardation is important. Among ethnic
      Norwegian women pelvic girdle pain and exhaustion were common complaints.

PMID- 10887459
TI  - Adverse birth outcomes among Mexican-Americans: are US-born women at greater risk
      than Mexico-born women?
AB  - OBJECTIVE: We examined adverse birth outcomes among Mexican-Americans to
      determine the effect of country of maternal birth, a measure of acculturation.
      DESIGN: We conducted a retrospective cohort analysis of birth outcomes among 4800
      Mexico-born and 4800 US-born Mexican-American women using Washington State birth
      certificate data from 1989 to 1994. Length of residence at current address was
      used to help refine our measure of acculturation. RESULTS: US-born women had a
      slightly increased risk of preterm birth relative to Mexico-born women [relative
      risk (RR) 1.18, 95% confidence interval (CI) 1.04-1.33]. Among Mexico-born women,
      the risk of preterm birth increased with greater duration of current residence.
      CONCLUSIONS: US-born Mexican-American women had a slightly increased risk of
      preterm birth despite having more adequate prenatal care, more education, and
      higher socioeconomic indicators. This may be due to acculturation factors, such
      as earlier pregnancy, loss of social support systems, and increased smoking or
      alcohol use. Reducing this risk depends on recognition among health care workers
      and policy-makers of the potential influence of acculturation on health in this
      population.

PMID- 10887460
TI  - Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution.
AB  - We undertook a retrospective analysis of the prevalence of obstetric cholestasis
      in the population of the South Birmingham area in the various ethnic subgroups. A
      diagnosis of intrahepatic cholestasis of pregnancy was made on the basis of
      symptoms of generalised pruritus along with biochemical evidence of the
      condition, after ruling out other liver diseases. We found an overall prevalence
      of 0.7%, with an occurrence in the white population of 0.62%, compared to that in
      the Asians of Pakistani origin of 1.46%. In the Asians of Indian origin it was
      found to be 1.24%. The prevalence of obstetric cholestasis was significantly
      higher in the Pakistani and Indian subgroups compared to the whites.

PMID- 10887461
TI  - Racial differences in symptoms and complications in adults with type 2 diabetes
      mellitus.
AB  - OBJECTIVE: To compare the frequency of common symptoms and complications between
      African- and white American adults with type 2 diabetes mellitus in a primary
      care setting, and to examine associations of these conditions with glycemic
      control. DESIGN: Three hundred and four adults with type 2 diabetes participated
      in this cross-sectional analysis; 142 of whom were African-Americans. Patients
      were recruited from a family practice ambulatory care unit and a community health
      center. RESULTS: Both male and female African-Americans had higher mean diastolic
      blood pressure and poorer metabolic control than their white counterparts. After
      adjustment for diabetes duration, glycosylated hemoglobin and diastolic blood
      pressure, African-American females were significantly more likely to experience
      constipation and hypertension but less likely to experience chest pain,
      claudication, peripheral neuropathy or have peripheral vascular disease. Among
      male subjects, African-Americans were significantly more likely to experience
      blurred vision and hypertension but less likely to have peripheral
      atherosclerotic disease. Poor glycemic control was more strongly associated with
      the occurrence of common diabetic symptoms in African-American subjects.
      CONCLUSIONS: Both African- and white Americans with type 2 diabetes are likely to
      experience a wide variety of symptoms and vascular complications. African
      American subjects appear more likely than whites to experience symptoms related
      to glycemic control but less likely to have, or experience symptoms and
      complications of, cardiovascular disease. That nearly half of these subjects seen
      in a primary care setting had microalbuminuria suggests that vascular
      complications are likely to be present in the majority of adults with type 2
      diabetes, even in these currently asymptomatic. These findings may have
      implications for screening and preventive strategies for the treatment of this
      disease.

PMID- 10887462
TI  - The conceptual validity and appropriateness of using health-related quality of
      life measures with minority ethnic groups.
AB  - Health-related quality of life measures have become increasingly used in the
      evaluation of health care to provide a measure of patients' subjective health
      status. Although studies often include ethnically heterogeneous samples, it is
      not clear to what extent the use of quality of life measures in this context is
      valid, because culture can affect the perception and interpretation of health and
      illness and so may affect the responses to items in a questionnaire. Such use
      also assumes the appropriateness of using a questionnaire format with individuals
      from different cultural backgrounds. This paper questions the assumptions of
      universality of concept and method, and presents the findings of a study which
      explored the conceptual validity and appropriateness of using the one health
      related quality of life measure, the Short Form-36 with a group of Indian cardiac
      patients. The study identified some differences between a matched control group
      and Indian patients. The implications of these results and the importance of
      considering culture in the measurement of health-related quality of life are
      discussed.

PMID- 10887463
TI  - The health of Bosnian refugees in Canada.
AB  - Many investigators of refugee health have assumed that due to the stresses
      associated with trauma and forced resettlement, refugees experience more
      pathology and resulting poor health than their host populations. However, because
      contradictory findings have emerged from some of these studies, a clear
      connection between the experiences of trauma, resettlement and health remain
      ambiguous. OBJECTIVES: The goal of this descriptive study was to put aside
      initial assumptions pertaining to the health of Bosnian refugees in the study.
      Rather, health was defined primarily by participants, through personal
      descriptions and perceptions of their experiences and associated health over
      time. DESIGN: Ten Bosnian refugees were selected according to age, gender,
      ability to speak English, and period of time in Canada. Each participant was
      interviewed on three occasions over a 3-month period in order to gather
      information pertaining to their experiences and health. Qualitative and
      quantitative methods were triangulated, that is, an informal, unstructured
      interview was augmented by investigator observations and structured health and
      demographic questions. RESULTS: The findings have shown that while war trauma and
      forced resettlement indeed posed serious risks to participants' health, on
      balance, they verbalized and were observed to be experiencing positive health and
      function. CONCLUSIONS: The ability of experience positive health and function in
      varying degrees following exposure to war trauma and forced resettlement appeared
      to be largely due to interactions between life events and cumulative personal,
      psychosocial, and cultural characteristics over time that modified the health
      risks associated with war trauma and forced resettlement.

PMID- 10887464
TI  - Cancer incidence among first generation Scottish, Irish, West Indian and South
      Asian migrants living in England and Wales.
AB  - OBJECTIVES: To examine the incidence of cancers among persons born in Scotland,
      Northern Ireland, the Irish Republic, Caribbean Commonwealth and Indian
      subcontinent and living in England and Wales. METHODS: Longitudinal Study of 1%
      of population of England and Wales followed from 1971 to 1989. Standardised
      incidence ratios (SIRs) were derived for commonly occurring cancers and all
      cancers using the age-sex-specific rates for all females and all males in the
      Longitudinal Study. RESULTS: The incidence of all malignant neoplasms among West
      Indians (females SIR = 67, male SIR = 70) and Indians (female SIR = 32, male SIR
      = 52) was low. Among South Asians, this pattern was consistent for Hindus, Sikhs
      and Moslems. Scottish females showed raised incidence of lung cancer (SIR = 149)
      and those from the Irish Republic of oral cavity and pharynx (SIR = 321),
      oesophageal (SIR = 219) and liver (SIR = 373) cancers. Among Northern Irish
      females, incidence of lung cancer (SIR = 193) was raised. West Indian and South
      Asian females showed low incidence of breast cancer (SIR = 55 and 45,
      respectively). High incidence of laryngeal (SIR = 229) and renal (SIR = 203)
      cancers was observed for Scottish males and of oral cancer (SIR = 259) for males
      from the Irish Republic. At ages 15-64, raised incidence of prostate cancer (SIR
      = 129) and of leukaemia (SIR = 252) was also observed for men from the Irish
      Republic. Northern Irish males showed raised incidence of stomach cancer (SIR =
      200). CONCLUSION: This study describes patterns of cancer incidence among migrant
      groups, most of which reflect environmental influences. This has challenging
      implications for sensitive targeting of primary interventions. It is important
      not to be complacent about lower risks of main cancers among West Indians and
      South Asians. In all Longitudinal Study members, breast cancer was the most
      common malignancy among females and lung cancer among males. This was also true
      for all migrant groups with the exception of Northern Irish women for whom lung
      cancer was the most common.

PMID- 10887465
TI  - Cirrhosis and primary liver cancer amongst first generation migrants in England
      and Wales.
AB  - OBJECTIVE: To examine mortality from cirrhosis of the liver and primary liver
      cancer among first generation migrants to England and Wales. DESIGN: Comparison
      of standardised mortality ratios (SMRs) for cirrhosis of the liver and primary
      liver cancer in men and women aged 20-69, by country of birth for the five year
      period 1988-1992. SETTING: England and Wales. RESULTS: There was a statistically
      significant two-fold excess of mortality from cirrhosis of the liver among male
      migrants from East Africa (SMR 286), India (SMR 261) and Bangladesh (SMR 254) as
      well as men born in Scotland (SMR 253) and Ireland (SMR252). Among women, only
      those born in Scotland (SMR 254) and Ireland (SMR 237) showed significant excess
      mortality. For liver cancer, significant excess mortality occurred among men born
      in the Caribbean (SMR 312), Bangladesh (910) and the African Commonwealth other
      than East Africa (1014), with Scottish and Irish born men showing more moderate
      excesses (136 and 170, respectively). SMRs were elevated also in all groups of
      foreign-born women but, probably owing to the small numbers of deaths, none of
      the findings reached statistical significance. CONCLUSIONS: Of public health
      concern is the excess mortality from cirrhosis in first generation immigrants to
      England and Wales from Scotland and Ireland (men and women) and in male migrants
      from India, Bangladesh and East Africa. Of equal concern is increased mortality
      from liver cancer in all foreign-born groups of both sexes, particularly among
      Bangladeshis, and African-Caribbeans. As well as promoting sensible drinking
      among immigrant men, specific preventive measures for those of Bangladeshi,
      African-Caribbean origin may include selective screening for hepatitis B and C
      and other tumour markers. Screening for liver cancer using imaging techniques
      needs further investigation. The benefit/cost ratio should be assessed by the
      Screening Committees of the UK Departments of Health. At local level, variation
      in incidence and prevalence of hepatic disease and feasible prevention programmes
      should be assessed within developing health improvement programmes.

PMID- 10887466
TI  - Perceptions of community services among Asian and white stroke survivors and
      their carers: an exploratory study.

PMID- 10887467
TI  - National oral health survey Zimbabwe 1995: dental caries situation.
AB  - Ten years after completion of the first national oral health survey, the second
      such survey was carried out in 1995. Application of a multi-stage sampling
      procedure resulted in 3,709 persons being examined according to the WHO oral
      health assessment form and criteria. The background variables studied were age,
      gender, type of location, socio-economic status. Comparison with results from
      major studies in other African nations are presented. It was concluded that the
      prevalence of dental caries in all age groups was high but that the severity was
      low. The prevalence of unmet treatment needs was very high with extraction as the
      predominant mode of treatment. The survey has shown that the vast majority of
      Zimbabweans are not receiving and/or are not seeking oral care.

PMID- 10887468
TI  - National oral health survey Zimbabwe 1995: periodontal conditions.
AB  - Ten years after completion of the first national oral health survey, a second
      national oral health survey was carried out in 1995. Application of a multi-stage
      sampling procedure resulted in 3,709 persons being examined. WHO's oral health
      assessment form and CPITN index was used. The background variables studied were
      age (15-19, and 35-44-year olds), gender, type of location, socio-economic status
      and level of education. Results suggest that the periodontal health of
      adolescents was better in 1985 than in 1995. Overall, the prevalence of
      periodontal conditions in both age groups was high but its severity was low. The
      need for complex periodontal treatment was only 4 per cent for adults. The survey
      has shown that the vast majority of Zimbabweans are not receiving and/or are not
      seeking periodontal care.

PMID- 10887469
TI  - Caries-risk assessment.
AB  - Dental caries has a multifactorial aetiology in which there is an interplay of
      three principal factors: the host (saliva and teeth), the microflora (plaque),
      and the substrate (diet), and a fourth factor: time. There is no single test that
      takes into consideration all these factors and can accurately predict an
      individual's susceptibility to caries. The risk of dental caries can be evaluated
      by analysing and integrating several causative factors. These include caries
      experience (initial caries lesions and established caries defects, secondary
      caries and present caries activity), fluoride use, extent of plaque present,
      diet, bacterial and salivary activity and social and behavioural factors.

PMID- 10887470
TI  - Future trends in oral health and disease.
AB  - The World Health Report, published annually by the World Health Organization,
      provides a rich source of information from which trends may be distinguished and
      planning can be initiated. In terms of oral health, trends in caries prevalence
      are of particular importance, as are developments in health promotion in general,
      which touch on life style factors and thus oral health decisions. This paper
      highlights aspects of the Report in relation to oral health and discusses some of
      WHO's responses to the global problems associated with improving oral health.

PMID- 10887471
TI  - Oral health and microflora in an institutionalised elderly population in Canada.
AB  - A cross-sectional study was undertaken to assess the oral health of a group of
      elderly, long-term care, institutionalised residents in a facility in Edmonton,
      Canada. In addition, the oral occurrence of Candida and coliform micro-organisms
      was evaluated to examine the relationship between oral health status and oral
      prevalence of these opportunistic pathogens. The mean age of 63 examined
      individuals was 83.4 (+/- 17.6) years; 28.6 per cent were dentate with a DMF
      score of 22.4; 4.5 per cent of teeth exhibited root caries. Of the edentate, 55.5
      per cent were wearing complete maxillary and mandibular dentures; 59 per cent of
      the maxillary dentures and 20 per cent of mandibular dentures were found to
      exhibit good retention and stability while the remaining prostheses were deemed
      to be poor; 17 per cent of individuals had neither teeth or dentures. Denture
      stomatitis was the most common mucosal lesion and was found amongst one third of
      the denture wearers. Three quarters of the residents harboured oral yeasts, 30
      per cent coliforms and a significant number exhibited poor oral hygiene and oral
      pathoses for which remedial treatment was readily available in the form of
      subsidised dental care.

PMID- 10887472
TI  - Occlusal registration: science or art?
AB  - Most of the information available to guide the clinician in making occlusal
      records focuses on the clinical techniques and methods involved. There is little
      objective information regarding the use of the more recently introduced
      elastomeric materials which are growing in popularity in the clinic. Much of the
      published work relies on the clinical experience of the authors rather than the
      properties of the material to be used to make the occlusal records. This paper
      aims to review the materials currently available to clinicians for use in
      occlusal registrations. The materials are discussed with regard to their
      suitability for the task and suggestions given regarding their use. Setting aside
      considerations of technique, it is suggested that there would be value in basing
      the selection of materials for occlusal registration on objective research.
      However, it may well be that the technique, as with many other things in
      dentistry, is as important as the specific properties of the materials used.

PMID- 10887473
TI  - In vitro, relative microleakage of five restorative systems.
AB  - The purpose of this study was to determine the relative microleakage of five
      restorative systems when bonded to dentine/cementum. For the microleakage
      determination Class V cavity preparations were prepared on the facial surfaces of
      65 teeth (10-15 for each material) below the cemento-enamel junction and
      restored. The root apices were sealed, the teeth coated with nail varnish except
      for 1 mm surrounding the restorations and the specimens were thermocycled (x500)
      in 2 per cent methylene blue solution. Root sections including the restorations
      were dissolved in acid and the concentrations of the dye determined
      spectrophotometrically. The sequence of the microleakage values were: Dyract <
      OptiBond < AeliteBond < All-Bond 2 < ScotchBond. It is concluded that Dyract had
      the lowest microleakage at dentine/cementum interface, which may increase the
      longevity of the restorative in the clinical situation, with no, or less
      secondary caries.

PMID- 10887474
TI  - Patients' satisfaction with dental services provided by a university in Hong
      Kong.
AB  - This study was a consumer evaluation of the dental care services provided by a
      university dental clinic in Hong Kong which provides dental care to all
      university students and staff and their dependents. The objectives of this study
      were to study the consumers' satisfaction with the dental services; to identify
      their reasons for not using the dental services; and to compare the opinions of
      the students with those of the university staff and their spouses. A total of 140
      students and 180 staff and their spouses were randomly selected for this study.
      The response rates were 100 per cent for students and 77 per cent for staff and
      their spouses. Results showed that both groups of respondents were satisfied with
      the quality of dental services provided by the university dental clinic. However,
      they were not satisfied with the long waiting time for an appointment. Students
      who had not attended the university dental clinic commonly stated that they were
      busy and had no time for a dental visit. Conversely, many staff and their spouses
      did not seek care from the university dental clinic because they thought that the
      fees were high. Although the overall Dental Satisfaction Index (DSI) scores for
      the students (64.5) and staff and their spouses (65.1) were similar, there were
      differences in the aspects of the services with which the two group were
      satisfied or dissatisfied. Thus if the university dental clinic wants to
      implement changes so as to improve consumer satisfaction and utilisation, a
      careful analysis of the specific opinions of its various consumer groups is
      required.

PMID- 10887475
TI  - Cardiovascular responses in patients and dentists during dental treatment.
AB  - Changes in mean heart rate and in mean systolic and diastolic blood pressure are
      induced by both the patient's anticipation of scheduled treatment and the actual
      dental treatment. Most of these changes are within the normal physiological
      variations, but significant changes are observed before administration of a local
      anaesthetic, during subgingival debridement and during extractions. Individual
      changes in heart rate and blood pressure are affected by age, gender,
      hypertension and previous dental experience. Pain also plays an important role in
      the cardiovascular response during dental treatment, which stresses the need for
      adequate analgesia. For this purpose, local anaesthetics with low concentrations
      of epinephrine seem preferable. They induce less pronounced cardiovascular
      responses than local anaesthetics with higher concentrations of epinephrine or
      without epinephrine. The changes in heart rate and blood pressure that occur in
      the dentist during the treatment are also discussed.

PMID- 10887476
TI  - Experimental models of development, function, and neoplasia.

PMID- 10887477
TI  - The mammary gland: a unique organ for the study of development and tumorigenesis.
AB  - The microanatomy and development of the mammary gland are unique and a reflection
      of its function to synthesize and deliver milk to the newborn offspring. The
      uniqueness of the mammary gland resides in several factors. First, the mammary
      parenchyma undergoes the vast majority of its growth postpubertally, thus
      enabling experiments on development to be performed in the juvenile or adult and
      presenting opportunities for experimental manipulation of the gland not available
      with other organs. On the basis of this characteristic, the fat pad
      transplantation method was developed, which resulted in the elaboration of
      important concepts in senescence, immortalization, and preneoplasia. Second, the
      accessibility of the gland and the ductal organization allows delivery and
      localization of specific molecules to mammary parenchyma cells, the cells which
      are the site of origin of neoplastic development. Third, the organ is the target
      of viral, chemical, and physical carcinogens, allowing development of unique and
      complex models for neoplastic development. Finally, the complexity of hormone and
      growth factor regulation of mammary gland function allows a sophisticated
      approach to the study of hormone action. The purpose of this review is to
      illustrate some unique properties of the gland which provide the basis for
      specialized approaches to developmental, neoplastic, and functional problems.

PMID- 10887478
TI  - Role of mesenchymal-epithelial interactions in mammary gland development.
AB  - The mammary gland is a hormone-target organ derived from epidermis and develops
      as a result of reciprocal mesenchymal-epithelial interactions. The induction of
      mammary differentiation from indifferent epidermal cells by mammary mesenchyme
      implies induction of the complement of hormone receptors characteristic of normal
      mammary epithelium in cells of the epidermis. Considering the facts that mammary
      epithelial differentiation is induced by mammary mesenchyme and that certain
      aspects of hormone response (androgen-induced mammary regression) are
      inextricably linked to mesenchymal-epithelial interactions, it is evident that
      the biology of the mammary gland arises from and is maintained via cell-cell
      interactions. As a corollary, perturbation of stromal-epithelial interactions in
      adulthood may play a role in mammary carcinogenesis and in turn may provide
      opportunities for differentiation therapy.

PMID- 10887479
TI  - Mammary tumorigenesis and chemoprevention studies in carcinogen-treated rats.
AB  - The objectives of this review are to describe the induction of mammary gland
      tumors by chemical carcinogens and to discuss their application to mammary cancer
      chemoprevention research. Special emphasis will be placed on the
      dimethylbenz[a]anthracene (DMBA) and methylnitrosourea (MNU) models because of
      the extensive information available about the pathogenesis of tumor growth
      associated with these two compounds. Both models have been widely used in the
      investigation of novel cancer chemopreventive agents. The current status of a
      number of different approaches will be summarized briefly here to provide an
      overview of research opportunities. Despite the popularity of the DMBA and MNU
      models in laboratory studies of mammary cancer biology and prevention, neither of
      these carcinogens has ever been implicated in the etiology of human breast
      cancer. This shortcoming has prompted a growing interest in other relevant
      environmental chemicals which are capable of producing mammary tumors in
      experimental animals. The new models have yet to be fully characterized, but they
      may be more appropriate than the DMBA and MNU models as paradigms for assessing
      cancer risk in humans and for developing suitable cancer prevention strategies.

PMID- 10887480
TI  - Tumor viruses and endogenous retrotransposons in mammary tumorigenesis.
AB  - Much of our knowledge about the intricate pathways and molecular mechanisms
      involved in the conversion of a normal mammary epithelial cell to malignancy
      derives from studies on mammary tumorigenesis induced by the retrovirus mouse
      mammary tumor virus. In addition, three DNA tumor viruses, simian virus 40,
      polyomavirus, and human papillomavirus, have been instrumental in dissecting the
      series of steps comprising neoplastic progression of mammary epithelium,
      particularly with cultured human breast cells. Endogenous transposons are
      analogous bioagents receiving increased attention recently. At least 10% of the
      cell genome consists of transposable elements, a growing number of which have
      been implicated in mutagenizing DNA in a variety of human tissues and disorders.
      Research efforts have therefore intensified to determine if endogenous elements
      such as retrotransposons participate in the development of breast cancer in
      animals and humans.

PMID- 10887481
TI  - The biology of mammary transgenes: five rules.
AB  - The development of hyperplasias, dysplasias, and mammary tumors has been studied
      extensively in transgenic mice. It is now becoming clear that transgenes activate
      and participate in oncogenic pathways that govern the events surrounding
      neoplastic progression in transgenic mice. The oncogenic pathways control mammary
      growth, development, and neoplastic progression. Some of the key features of
      transgenic biology can be expressed in the following rules: (1) Mammary
      development is related to the type and amount of transgene expressed; (2)
      dysplasias and tumors develop from secondary mutations; (3) the transgenes
      determine tumor phenotype; (4) transgenes may activate dominant oncogenic
      pathways; and (5) the oncogenic pathway determines prognosis. The study of the
      comparative pathology of mammary tumorigenesis in many strains of transgenic mice
      provides examples of these principles.

PMID- 10887482
TI  - Genetic manipulation of mammary epithelium by transplantation.
AB  - Genes can be introduced into mammary epithelium in vivo by the 'tissue
      reconstitution' method. Primary cultures of mammary epithelial cells are
      prepared, a gene introduced using retrovirus vectors, and the cells transplanted
      into a mammary fat pad from which the normal epithelium has been removed. The
      cells reform an epithelium in which some cells express the introduced gene. The
      technique is reviewed and compared with the mammary-specific expression of genes
      in transgenic mice. To model the development of neoplasia, particularly the
      preneoplastic changes caused by a single oncogene alone, several oncogenes have
      been expressed this way--myc, Ha-ras, erbB, erbB2, Wnt-1, and hst/FGF-4. Each
      caused a different alteration to the growth pattern of the epithelium, such as
      altered branching, premature alveolus development, distorted duct structure, or
      altered hormone sensitivity. Insights into normal development have also been
      obtained by inappropriate expression of genes such as Wnt-4.

PMID- 10887483
TI  - Three-dimensional mammary primary culture model systems.
AB  - Model systems have been developed to investigate the complex and coordinated
      regulation of mammary gland development and transformation. Primary cultures,
      using newly isolated cells or tissue, are optimal for such studies since, in
      comparison to immortalized cell lines, the normal signal transduction pathways
      are presumed to be intact. Three such models are described, including whole organ
      culture, mammary epithelial cell (MEC) organoids, and MEC-stromal cocultures.
      Studies using whole-organ culture have the advantage that the normal glandular
      architecture remains intact, the MEC can undergo lobuloalveolar development and
      express milk proteins in a hormone dependent manner, and, following hormonal
      withdrawal, undergo involution. Moreover, transformation of the MEC is readily
      accomplished. Culture of isolated MEC organoids within an EHS-derived
      reconstituted basement membrane permits extensive proliferation, branching end
      bud and alveolar morphogenesis, and accumulation of milk protein and lipid in a
      physiologically relevant hormone- and growth factor-dependent manner. This model
      can thus be utilized to investigate the mechanism by which various modulators
      exert their direct effects on the epithelium. Finally, in view of compelling
      evidence for stromal-epithelial interactions during normal mammary gland
      development, and potentially also during the development of malignancy, models in
      which MEC can be cocultured with enriched populations of stroma offer
      considerable potential as a tool to understand the nature and mechanisms of the
      interactions that occur during the various developmental states, and how such
      interactions may go awry during carcinogenesis.

PMID- 10887484
TI  - Human breast cancer cell lines as models of growth regulation and disease
      progression.
AB  - The routine isolation and culture of human breast cancer cells from patient
      samples has been a goal of breast cancer cell biologists for over 30 years.
      Despite extensive work in this area and the development of many human breast
      cancer cell lines, the proportion of patient samples that give rise to
      immortalized breast cancer cell lines is still disappointingly low. The majority
      of human breast cancer cell lines that have been established were isolated many
      years ago and have been grown continuously under poorly defined culture
      conditions. These cell lines have been useful for studies of the estrogen
      receptor biology in human breast cancer cells, in identifying growth factors
      synthesized by breast cancer cells, and for the characterization of genetic
      alterations in oncogenes and tumor suppressor genes present in these cells. More
      recently, tissue culture methods have improved, resulting in the ability to
      culture routinely normal human mammary epithelial cells of specific lineages and
      this has resulted in the development of new human breast cancer cell lines. The
      ability to isolate and culture normal and neoplastic human mammary epithelial
      cells under similar culture conditions has improved these models dramatically and
      has resulted in the identification of altered cellular phenotypes of human breast
      cancer cells.

PMID- 10887485
TI  - Animal models for the study of milk secretion.
AB  - Milk secretion is regulated by a complex interaction of galactopoietic hormones
      which is not yet fully understood. Recent studies have demonstrated that this
      systemic control is modulated within the mammary gland by local mechanisms
      responsive to the frequency and completeness of milk removal. New insights into
      the endocrine and local (paracrine and autocrine) regulation of milk secretion
      have come from the adaptation of traditional endocrinological techniques to take
      advantage of new molecular tools, and from technical advances in other fields.
      This paper reviews recently developed animal models for the study of milk
      secretion and describes their application to provide new information into the
      roles of two key galactopoietic hormones, growth hormone and prolactin, and the
      modulation of their actions by local, intramammary mechanisms.

PMID- 10887486
TI  - Dedication: Clifford W. Welsch.

PMID- 10887487
TI  - Molecular aspects of breast cancer.

PMID- 10887489
TI  - Cyclins and breast cancer.
AB  - Recent advances in the understanding of cell cycle control by cyclins and cyclin
      dependent kinases provide a basis for delineating the molecular mechanisms of
      proliferation control by steroids and the development and progression of hormone
      dependent cancers. Cyclin D1 is necessary, rate-limiting and sufficient for G1
      progression in breast cancer cells and regulation of cyclin D1 expression or
      function is an early response to steroid and steroid antagonist regulation of
      proliferation. The cyclin D1 gene is amplified in approximately 15%, and its
      product overexpressed in 40-50%, of primary breast carcinomas. The strong
      evidence that cyclin D1 plays a major role in cell cycle control in breast
      epithelial cells suggests that its deregulated expression may have effects on
      disease progression and phenotype including sensitivity to endocrine therapies.

PMID- 10887488
TI  - Genetic analysis of breast cancer progression.
AB  - At the histological level, breast tumors display a variety of morphologic lesions
      which suggest the existence of an increasingly aberrant pathway of intermediate
      steps leading to the invasive primary tumor and its metastatic dissemination. In
      order to obtain direct evidence for this presumed progression, underlying genetic
      changes must be identified. Analyses of primary breast tumors have revealed a
      large number of dominant and recessive gene alterations encompassing several
      cellular attributes and activities. It is quite likely that some of these
      alterations are of a causal nature and thus enable the tumor to attain
      distinctive malignant phenotypes, such as, dysregulated proliferation, invasion,
      angiogenesis, and ability to metastasize. Considerable heterogeneity has been
      observed in the sequence of acquisition of these genetic changes, which is
      substantiated by recent comparative analyses between carefully microdissected
      preinvasive and invasive tumor. The data are evaluated here in the context of
      existing models of breast cancer progression. Implication and prospects for
      translational application to the clinic are also discussed.

PMID- 10887490
TI  - P53, apoptosis, and breast cancer.
AB  - Wild-type p53 is a tumor suppressor gene that plays a central role in maintaining
      the genetic integrity of the cell by preventing cells with damaged DNA from
      further proliferation. Mutation and deletion of p53 are the most common genetic
      defects seen in clinical cancer. About 40% of breast carcinomas show high levels
      of stabilized, often mutant, p53 protein in their cells as detected by
      immunohistochemistry. p53-related defects in tumor cells correlate with a poor
      prognosis and may also indicate a poor response to chemotherapy. In experimental
      systems, the p53 status of cells is important in determining their sensitivity to
      radiation and chemotherapeutic drugs. Cells with functional p53 die by apoptosis,
      whilst similar cells lacking p53 function continue to proliferate, perpetuating
      potentially oncogenic mutations. Not only may p53 status be a marker of the
      biological aggressiveness of individual tumors and of their likely response to
      therapy, but restoration of normal p53 function is itself already a goal of
      cancer therapy.

PMID- 10887491
TI  - Protein kinase C isozymes and substrates in mammary carcinogenesis.
AB  - Protein kinase C (PKC) comprises a family of ubiquitously expressed phospholipid
      dependent enzymes that regulate cell growth and differentiation. Several
      effectors that modify mammary cell biology work at least partially through PKC
      dependent pathways. Studies with mammary epithelial cells and tissues have
      demonstrated probable roles for the PKCs in processes associated with
      carcinogenesis including proliferation, estrogen sensitivity, and apoptosis. The
      involvement of PKCs in this wide variety of responses may in part be explained by
      the expression of multiple PKCs in breast tissue and the possibility that
      individual PKCs selectively phosphorylate different proteins and preferentially
      mediate different biological responses. Further understanding of the role of
      individual PKCs in mammary cell growth and tumor promotion/progression is likely
      to lead to new insights for breast cancer diagnosis and treatment.

PMID- 10887492
TI  - Growth factor and sex steroid interactions in breast cancer.
AB  - Mitogenic and inhibitory growth factors and steroid ovarian hormones play
      important roles as selective modulators of normal mammary development and in the
      onset and the progression of human breast cancer. The focus of this article is to
      review past and current research on the interactions of these two classes of
      effectors in mammary gland development and neoplasia. Steroid hormones regulate
      synthesis of growth stimulatory and inhibitory growth factors, growth factor
      receptors, and growth factor binding proteins. In turn, growth factor pathways
      may modulate phosphorylation and function of steroid receptors and potentiate or
      inhibit the mitogenic actions of steroids. Ultimately, during the progression of
      the malignant mammary epithelial cell to hormonal autonomy, overexpression,
      mutation, or disregulation of key elements of growth factor signal transduction
      pathways all may play critical roles.

PMID- 10887493
TI  - ErbB2 activation and signal transduction in normal and malignant mammary cells.
AB  - One of the first consistent genetic alterations found in human breast tumors was
      amplification of the erbB-2 gene leading to overexpression of the protein. ErbB2
      is a member of the ErbB/type I family of receptor tyrosine kinases which also
      includes epidermal growth factor receptor, ErbB3 and ErbB4. The role of ErbB2 in
      the biology of the mammary gland as well as in breast cancer development is under
      intense investigation. In clinical studies, the ErbB2 protein level has been
      examined for its utility in predicting patient prognosis and response to
      treatment. The ErbB2 receptor is also being tested as a target for tumor directed
      therapies.

PMID- 10887494
TI  - Cell adhesion molecules in the normal and cancerous mammary gland.
AB  - Loss of normal tissue morphology is one of the first changes seen in the
      development of solid malignant tumours, including breast cancers. Since cell
      adhesion molecules play a crucial role in maintaining normal tissue architecture,
      investigations into the molecular mechanisms involved in the morphological
      changes occurring in malignancy that focus on the expression and function of cell
      adhesion molecules in malignant progression are extremely relevant. This review
      discusses the cadherin and integrin families of adhesion molecules which have
      been shown to be extremely important in the cell-cell and cell-matrix
      interactions of epithelial cells. Immunohistochemical studies using tissue and
      tumour sections indicate that a reduction in levels of expression or function of
      both types of cell adhesion molecules is indeed observed in many breast cancers.
      A specific and crucial role for these molecules in the maintenance of normal
      morphological differentiation has been demonstrated in vitro, where the
      noninvasive differentiated phenotype correlates with the normal functioning of E
      Cadherin and alpha 2 beta 1 integrin. Further in vitro evidence suggests that in
      mammary epithelial cells, oncogenes may be upstream regulators of both the
      expression and function of E-Cadherin, the alpha 2 beta 1 integrin, and other
      epithelial specific molecules important for maintaining epithelial
      differentiation. In this way they could manifest their effects on the
      tumorigeneic potential of epithelial cells.

PMID- 10887495
TI  - The role of cadherin-mediated adhesion in breast cancer.
AB  - The cell adhesion molecule E-cadherin is expressed on the basolateral surfaces of
      normal mammary epithelial cells and is lost in a subset of breast cancers. Loss
      of E-cadherin expression has been postulated to facilitate tumor cell detachment
      from a primary tumor ultimately leading to metastasis. In this paper, I review
      the published in vitro data that initially supported this "invasion suppressor"
      role for E-cadherin as well as more recent in vitro and in vivo data showing that
      E-cadherin-positive tumor cells can metastasize. I examine other molecules
      required for E-cadherin function and discuss how defects in the expression or
      function of these molecules might alter E-cadherin function in E-cadherin
      positive tumor cells. For example, loss of expression or function of catenins,
      intracellular molecules that interact with E-cadherin, can result in the loss of
      E-cadherin-mediated adhesion and a more invasive phenotype. Altered
      phosphorylation of E-cadherin or catenins can also influence E-cadherin function.
      Finally, expression of other cell surface molecules such as mucins may interfere
      with E-cadherin function. The collective effect of these molecules on the
      adhesive phenotype of breast cancer cells may be one determinant of metastatic
      potential.

PMID- 10887497
TI  - Bioactive components of milk.

PMID- 10887496
TI  - Stromelysin-3 in the biology of the normal and neoplastic mammary gland.
AB  - Stromelysin-3 (ST3) is an extracellular proteinase predominantly expressed in
      fibroblasts. The particular structural features and in vitro functions of this
      molecule suggest it could be the first member of a new subgroup of the matrix
      metalloproteinase family. ST3 is transiently expressed during mammary gland post
      weaning involution, embryonic implantation, various organogeneses, and during
      amphibian metamorphosis. Moreover, ST3 is expressed in a panel of human invasive
      carcinomas including breast, colon, and head and neck carcinomas. Almost all ST3
      expressing tissues show intense extracellular matrix remodeling activities
      including the loss of basement membrane integrity. Thus, either directly, or
      indirectly in association with other proteinases, ST3 might be involved in tissue
      remodeling processes occurring in both physiological and pathological processes.
      In vitro and in vivo studies using malignant cells stably transfected in such a
      way as to modulate their ST3 expression levels indicate that ST3 modifies neither
      cell proliferation nor invasive properties, but rather favors tumor cell survival
      in host tissues. This hypothesis is consistent with clinical data showing that
      ST3 expression could be predictive of tumor progression leading to metastases.

PMID- 10887498
TI  - Antibodies in milk.
AB  - The immaturity of the infant's immune system and the rapid evolution of pathogens
      has created a demand for the mother to provide ready made specific defence
      factors to her offspring. This is achieved during the fetal period by
      transplacental transport of IgG antibodies, and after birth via IgA antibodies in
      the breast milk. The breast milk also contains a variety of nonspecific defence
      factors contributing to its antimicrobial effect. Breast feeding has been shown
      to decrease morbidity in gastroenteritis, septicemia, otitis media, urinary tract
      infection, encephalitis, pneumonia, and necrotizing enterocolitis. The antibody
      content in the mother's milk probably contributes not only to the immediate but
      also to the long term protection of the infant including both resistance to
      infection and development of immunological tolerance to harmless environmental
      antigens.

PMID- 10887499
TI  - Cytokines in human milk: properties and potential effects upon the mammary gland
      and the neonate.
AB  - Epidemiologic and immunologic studies of breastfed and nonbreastfed infants and
      investigations of certain biologic activities in human milk led to the
      identification of immunomodulating agents in human milk. Among them were the
      cytokines interleukin-1 beta (IL-1 beta); IL-6, IL-8, IL-10, granulocyte-colony
      stimulating factor, macrophage-colony stimulating factor (M-CSF), tumor necrosis
      factor-alpha, interferon-gamma, epithelial growth factor (EGF), transforming
      growth factor-alpha (TGF-alpha), and TGF-beta 2. Interferon-gamma may originate
      from T cells in milk; EGF, TGF-alpha, TGF-beta, M-CSF, IL-6, and IL-8 may be
      produced by mammary gland epithelium. Based upon their known functions, we
      hypothesize that cytokines influence the development and immunologic function of
      the mammary gland and the neonate. Those in vivo functions remain to be defined
      by future investigations.

PMID- 10887500
TI  - Milk-borne prolactin and neonatal development.
AB  - Milk is primarily regarded as a food furnishing essential nutrients for infant
      growth and development, but milk can also serve as a vehicle for mother to
      neonate transfer of molecules that regulate development. A wide array of
      biologically active compounds such as hormones, cytokines and enzymes are present
      in milk, especially early milk. The premise that prolactin (PRL) in milk is an
      important and possibly essential developmental factor for the newborn is
      explored. Both PRL and structurally modified isoforms are abundant in early milk
      and gradually diminish with the progression of lactation. Milk PRL is absorbed
      and biologically active in the neonate. Assays of PRL variants, experimental
      paradigms to test them as developmental regulators and the body of evidence
      supporting the hypothesis that milk PRL regulates differentiation and maturation
      of neonatal neuroendocrine, reproductive, and immune systems is presented.

PMID- 10887501
TI  - Oligosaccharides and glycoconjugates in human milk: their role in host defense.
AB  - Human milk contains an extremely high concentration of complex carbohydrates,
      especially oligosaccharides, the third most abundant solid constituent of human
      milk. The value of human milk nutrients to infants is now widely recognized, and
      a role for the secretory antibodies of human milk in the defense of the infant is
      generally accepted. However, a function for nonimmunoglobulin milk protective
      factors, many of them non-nutrients, in providing for the defense of the nursling
      is only now beginning to be appreciated. Prominent among postulated defense
      agents are the milk oligosaccharides and glycoconjugates. Their complex
      carbohydrate structures are thought to be assembled by the same enzymes, the
      glycosyltransferases, that synthesize the cell surface glycoconjugates often used
      as receptors by pathogens. Some milk oligosaccharides and glycoconjugates may
      protect the nursing infant by acting as receptor homologs, inhibiting the binding
      of enteropathogens to their host receptors. Ongoing research is linking specific
      carbohydrate structures with protection against specific pathogens. Current
      information regarding the composition, protective activities, and protective
      mechanisms of the milk glycolipids, glycoproteins, mucins, glycosaminoglycans,
      and oligosaccharides is reviewed.

PMID- 10887502
TI  - Structure and biological actions of lactoferrin.
AB  - Lactoferrin is an iron-binding glycoprotein of the transferrin family, first
      isolated from milk but also found in most exocrine secretions as well as in the
      secondary granules of neutrophils. The many reports on its antimicrobial and
      antiinflammatory activity in vitro identify lactoferrin as important in host
      defense against infection and excessive inflammation. Most if not all lactoferrin
      actions are mediated through iron sequestration and/or interaction with a large
      variety of ligands including microbial cell wall components and cellular
      receptors, through its highly positively charged N-terminus. Lactoferrin exerts
      its effects on glandular epithelia, secretions, mucosal surfaces as well as in
      the interstitium and vascular compartments where it has been postulated to
      participate in iron metabolism, disease defense, and modulation of inflammatory
      and immune responses. A need to understand the diverse biological actions of
      lactoferrin and the prospect of a wide variety of potential applications in human
      health care have stimulated studies of the relation between lactoferrin structure
      and function, the regulation of lactoferrin secretion and development of large
      scale production of recombinant human lactoferrin (hLf). This review provides a
      synthesis of our current understanding of lactoferrin. Space limitations have led
      us to refer to review articles whenever possible; the reader is advised to use
      these articles for access to the primary experimental literature.

PMID- 10887503
TI  - Insulin-like growth factors in milk and mammary gland.
AB  - Milk contains insulin-like growth factor I and II (IGF-I and IGF-II) and four IGF
      binding proteins (IGFBP). Their concentrations are highest prepartum and early
      postpartum, coinciding with maximal proliferation of mammary cells and the time
      when the infant gut is the least developed. This has lead to the suggestion that
      IGFs may be important for the growth and development of the mammary gland and
      that IGFs in milk play a role in promoting development of the gastrointestinal
      tract of the newborn. IGF-I and, to a lesser extent, IGF-II can stimulate milk
      yield and blood flow in goats when infused directly into the mammary gland,
      suggesting they may also be important in supporting established lactation. Thus
      IGFs may have a dual function in the mammary gland, establishing and maintaining
      the maternal mammary system and, once secreted into milk, supporting
      gastrointestinal development in the newborn.

PMID- 10887504
TI  - Feedback control of milk secretion from milk.
AB  - Extracellular storage allows biologically-active substances in milk to influence
      mammary function. Among these factors is one which regulates the rate of milk
      secretion acutely according to frequency or completeness of milk removal in each
      mammary gland. The active factor in goat's milk has been identified by screening
      milk constituents for their ability to inhibit milk constituent secretion in
      tissue and cell culture bioassays, and found to be a novel milk protein. The
      proteins identified by bioassy in vitro, also inhibited milk secretion in
      lactating goats in a reversible, concentration-dependent manner. This protein,
      termed FIL (feedback inhibitor of lactation), acts by reversible blockade of
      constitutive secretion in the mammary epithelial cell. As the inhibitor is
      synthesized in the same epithelial cells, feedback inhibition is, therefore, an
      autocrine mechanism. FIL's unusual mechanism of action also influences other
      aspects of mammary function. Acute disruption of mammary membrane trafficking is
      associated with downregulation of prolactin receptors and followed by a decrease
      in epithelial cell differentiation. Thus, in addition to acutely-regulating milk
      secretion, FIL may induce the adaptation in mammary cell differentiation which
      acts in vivo to sustain the secretory response to a sustained change in milk
      removal. In the long term, matching of milk output to demand is achieved by a
      change in mammary cell number. This developmental response is also local in
      nature. Whether it too is due to autocrine modulation by FIL of mechanisms
      influencing cell proliferation or survival, or elicited by another milk-borne
      factor, remains to be determined.

PMID- 10887505
TI  - The potential physiological significance of milk-borne hormonally active
      substances for the neonate.
AB  - This article reviews the presence and potential physiological significance of
      hormones and hormonally active substances (including growth factors) in human
      milk. Human milk has been found to contain several nonpeptide hormones and many
      peptide hormones and growth factors. In contrast to human breast milk, infant
      formulae lack some hormonally active peptides. There is little data concerning
      the effects of these agents on human neonates. Studies in immature experimental
      animals showing effects of orogastically administered hormones are summarized.
      The problems of supplementation of infant formula are discussed. Since hormones
      are present in the milk as a "cocktail" of potentially agonistic and antagonistic
      substances, one question is whether supplementation with a single agent would
      disturb this balance.

PMID- 10887506
TI  - TGF-beta in mammary development and neoplasia.

PMID- 10887507
TI  - The role of TGF-beta in patterning and growth of the mammary ductal tree.
AB  - Evidence that transforming growth factor beta (TGF-beta) influences pattern
      formation in the developing mammary gland and negatively regulates ductal growth
      is reviewed. In the mouse, overexpression of TGF-beta transgenes during puberty
      reduces the rate of growth of the ductal tree and simplifies the pattern of
      arborization, while expression during pregnancy also interferes with lactation.
      Expression studies in the normal mouse gland indicate that TGF-beta is
      synthesized in the mammary epithelium, with the three isoforms showing somewhat
      different spatial and temporal distributions. Exogenous TGF-beta applied directly
      to the gland in situ inhibits epithelial cell division within hours, and strongly
      stimulates extracellular matrix synthesis over a longer time course. Normal human
      breast cells as well as certain breast cancer cell lines also secrete TGF-beta
      and are themselves inhibited by it, suggesting an autoregulatory feedback
      circuit, that in some cases appears to be modulated by estradiol. Taken together,
      the evidence suggests a model in which growth and patterning of the mammary
      ductal tree are regulated, at least in part, by TGF-beta operating through an
      autocrine feedback mechanism and by paracrine circuits associated with epithelial
      stromal interactions.

PMID- 10887509
TI  - Latency and activation in the control of TGF-beta.
AB  - The biological activity of the transforming growth factor-beta's (TGF-beta) is
      tightly controlled by their persistance in the extracellular compartment as
      latent complexes. Each of the three mammalian isoform genes encodes a product
      that is cleaved intracellularly to form two polypeptides, each of which
      dimerizes. Mature TGF-beta, a 24 kD homodimer, is noncovalently associated with
      the 80 kD latency-associated peptide (LAP). LAP is a fundamental component of TGF
      beta that is required for its efficient secretion, prevents it from binding to
      ubiquitous cell surface receptors, and maintains its availability in a large
      extracellular reservoir that is readily accessed by activation. This latent TGF
      beta complex (LTGF-beta) is secreted by all cells and is abundant both in
      circulating forms and bound to the extracellular matrix. Activation describes the
      collective events leading to the release of TGF-beta. Despite the importance of
      TGF-beta regulation of growth and differentiation in physiological and malignant
      tissue processes, remarkably little is known about the mechanisms of activation
      in situ. Recent studies of irradiated mammary gland reveal certain features of
      TGF-beta 1 activation that may shed light on its regulation and potential roles
      in the normal and neoplastic mammary gland.

PMID- 10887508
TI  - TGF-beta and functional differentiation.
AB  - A review of the pertinent literature suggests that TGF-beta 1 may play a
      multifaceted role in functional differentiation of mammary epithelium. Evidence
      for the expression of TGF-beta 1 RNA and the presence of functional TGF-beta 1
      protein in differentiating mammary epithelial cells from a pregnant mouse has
      been recently reported. The specific role of mammary-epithelial-cell-produced TGF
      beta 1 in the differentiating mammary gland is presently unclear. However,
      several possible functions are suggested from the following observations. Milk
      protein production is negatively regulated by exogenous TGF-beta 1 during
      gestational development of the gland but not during lactation. Consistent with
      reports linking TGF-beta 1 gene expression with mammary gland involution
      following lactation, overexpression of TGF-beta 1 in the differentiating
      secretory epithelium leads to premature programmed cell death in the absence of a
      negative effect on secretory epithelial cell proliferation. A role for TGF-beta 1
      in cell cycle control and suppression of malignant progression independent from
      its inhibitory effect on epithelial cell growth has been demonstrated in
      keratinocytes. A similar function could provide protection against malignancy in
      proliferating mammary epithelium and account for TGF-beta 1 suppression of
      mammary tumorigenesis in transgenic mice overexpressing transforming growth
      factor alpha (TGF-alpha).

PMID- 10887510
TI  - Defects of TGF-beta receptor signaling in mammary cell tumorigenesis.
AB  - Transforming growth factor beta (TGF-beta) receptor expression and signal
      transduction in human breast cancer are reviewed as a function of estrogen
      receptor (ER) expression. ER+ breast cancer cells are generally resistant to the
      inhibitory effects of TGF-beta. The only known exception appears to be MCF-7
      early passage cells which are initially sensitive to TGF-beta, but gain
      resistance after long-term passage in tissue culture. A number of studies have
      shown that loss of sensitivity is due to inadequate TGF-beta type II (TGFRII)
      receptor expression. Stable transfection of TGFRII into ER+ breast cancer cell
      lines results in the acquisition of TGF-beta sensitivity and reversion of
      malignancy. Although there are exceptions, ER- breast cancer cells usually
      express TGFRII, but nevertheless show a low level of sensitivity to TGF-beta.
      Thus resistance in these cells implies a postreceptor mechanism. Given the
      frequency with which loss of TGF-beta sensitivity has been associated with loss
      of TGFRII, the ER- breast cancer cell lines may represent valuable models for
      identifying postreceptor mechanisms of resistance.

PMID- 10887511
TI  - Complex role of tumor cell transforming growth factor (TGF)-beta s on breast
      carcinoma progression.
AB  - Growth inhibition by the TGF-beta s has been extensively studied in both normal
      and transformed mammary epithelial cells. It has been proposed that loss of
      autocrine TGF-beta mediated growth regulation is a critical event in breast
      tumorigenesis and several lines of in vitro and in vivo data support this
      hypothesis. However, a positive association between the expression of TGF-beta s
      by tumor cells and the progression or maintenance of breast cancinoma cells has
      been observed in many studies in in vivo tumor models. Possible mechanisms for
      these growth enhancing effects of TGF-beta include immunosuppression mediated by
      tumor TGF-beta s, enhanced angiogenesis, increased peritumoral stroma formation,
      and cell adhesion. The net effect of tumor cell TGF-beta on the biology of breast
      carcinogenesis would depend on the balance between autocrine growth inhibition of
      mammary epithelial cells and these growth enhancing effects.

PMID- 10887512
TI  - Role of TGF beta in the anti-estrogen response/resistance of human breast cancer.
AB  - Transforming growth factor beta (TGF beta) has potent inhibitory effects upon
      epithelial proliferation and malignant progression may be associated with
      breakdown of the autocrine and paracrine inhibitory loops in which TGF beta
      participates. The therapeutic effecs of anti-estrogens may be partially
      attributable to boosting of local endogenous levels of TGF beta. This article
      reviews the evidence in support of TGF beta being a proximate effector in
      mediation of the anti-neoplastic effects of anti-estrogens. Both the conventional
      estrogen receptor (ER) dependent and ER independent mechanisms of action are
      likely to be involved. Evidence for preferential stromal induction of TGF beta by
      anti-estrogens is emphasized, together with the therapeutic potential of this
      strategy for improving outcome in early breast cancer irrespective of ER status.

PMID- 10887513
TI  - Therapeutic implications of the TGF-beta system.
AB  - This review considers the various roles of the TGF-beta system in mammary
      carcinogenesis, tumor progression, and cellular responses to therapeutic
      measures. The paradigm that has evolved from the work of many investigators
      suggests that loss of tumor cell responsiveness to the effects of TGF-beta can
      result in a crucial shift in the net effect of TGF-beta within the context of the
      tumor-host interaction. Principal elements of host-tumor interactions in which
      this shift may play out, including immune suppression, angiogenesis, and
      modification of the surrounding extracellular matrix by tumor cells, are
      potentially amenable to manipulation. Additional effects of TGF-beta, such as
      suggested by reports of its ability to alter the drug resistance of tumor cells
      and the drug sensitivity of normal tissues, suggest that appropriate molecular
      intervention designed to affect the TGF-beta system might constitute an effective
      therapeutic strategy.

PMID- 10887514
TI  - Prolactin, growth hormones, and placental lactogens: an historical perspective.

PMID- 10887515
TI  - The prolactin/growth hormone receptor family: structure/function relationships.
AB  - Prolactin (PRL) and growth hormone (GH) receptors are members of the cytokine
      receptor superfamily that are activated by ligand-induced homodimerization. On
      the basis of this mechanism of activation, hormone antagonists have been
      developed that block the receptors in an inactive conformation. PRL and GH
      receptors are non-kinase receptors whose activation of signaling pathways
      requires participation of receptor-associated kinases, such as Janus kinases or
      Src kinases. Signal transduction by these receptors mainly involves the JAK/Stat
      pathway. In this review, we discuss the mechanism of ligand binding and receptor
      homodimerization as well as the involvement of molecules transducing the hormonal
      signal. Whenever possible, we attempt to correlate cytoplasmic features of the
      receptors with association and/or activation of transducer molecules or with a
      given biological property.

PMID- 10887516
TI  - Prolactin mediated intracellular signaling in mammary epithelial cells.
AB  - Prolactin binds to a member of the cytokine receptor superfamily. The cytoplasmic
      domain of the prolactin receptor (PrlR) displays no enzymatic activity yet
      prolactin treatment leads to the induction of protein tyrosine phosphorylation.
      PrlR is associated with JAK2, a protein tyrosine kinase whose activity is
      stimulated following receptor dimerization. JAK2 subsequently phosphorylates PrlR
      and other cellular proteins which are recruited to the activated receptor
      complex. Among the JAK2 substrates is the transcription factor Stat5 whose
      phosphorylation mediates the transcriptional activation of beta-casein gene
      expression. In this review we discuss the prolactin induced signaling pathways
      which mediate differentiation of the mammary gland.

PMID- 10887517
TI  - Prolactin as a mitogen in mammary cells.
AB  - Prolactin (PRL) acts as both a mitogen and a differentiating agent in the breast.
      The decision to respond to PRL as a mitogen by breast cells depends on the
      hormonal milieu in which the epithelial cell resides. In addition, PRL's action
      on the breast is regulated (1) at the level of the hormone itself; (2) at the
      receptor level; (3) at the level of selection of signaling pathway; and, (4) by
      combinations of these aspects. The development of cell lines containing only one
      class of the PRL receptors and showing qualitative differences in response and
      signaling pathways will help in understanding the pleiotropic nature of PRL
      action.

PMID- 10887518
TI  - Interactions of prolactin and growth hormone (GH) in the regulation of mammary
      gland function and epithelial cell survival.
AB  - The relative importance of GH and prolactin in mammary gland function varies
      between species with prolactin playing a major role in rodents and GH taking lead
      role in ruminants. In rodents, however, GH appears to play a vital role in
      maintaining a high-fat/low volume milk in the absence of prolactin and a similar
      finding has been demonstrated in goats where prolactin deficiency causes a more
      modest (15%) decrease in milk yield. Surprisingly GH-deficiency in goats induced
      no further decline in milk yield whereas exogenous GH or prolactin both
      stimulated milk output considerably. Although direct effects of prolactin on
      mammary epithelial cells are well-documented effects of GH are believed to be
      mediated indirectly via IGF-1 production from the liver. We have been unable to
      confirm this hypothesis in rats and believe this to be because it is too
      simplistic. By considering prolactin and GH to be survival factors for the
      mammary gland we now propose a mechanism by which they interact through the IGF
      system. Involution of the mammary gland involves apoptosis and, in rats, it is
      induced by prolactin-deficiency or milk accumulation. Coincidentally with this
      process mammary epithelial cells synthesize and secrete and IGF binding protein,
      IGFBP-5. We hypothesize that GH stimulates IGF-1 production, possibly from the
      mammary parenchyma. IGF-1 then acts as a survival factor for the mammary gland.
      Prolactin plays an essential role since it suppresses the secretion of IGFBP-5
      which would otherwise inhibit IGF-1 action and lead to the induction of cell
      death.

PMID- 10887519
TI  - Early mammary development: growth hormone and IGF-1.
AB  - The first step in pubertal mammary development is the appearance of terminal end
      buds arising from pleuropotent stem cells present in the immature ductal tree of
      the prepubertal animal. Work from this laboratory indicates that growth hormone
      is the pituitary hormone responsible for terminal end bud development. Growth
      hormone likely acts through the production of IGF-1. This minireview focuses on
      the hormonal control of early mammary development with special emphasis on the
      roles of growth hormone and IGF-1.

PMID- 10887520
TI  - Prolactin as an autocrine/paracrine factor in breast tissue.
AB  - The neuroendocrine hormone prolactin (PRL) stimulates breast growth and
      differentiation during puberty, pregnancy, and lactation. Despite extensive and
      convincing data indicating that PRL significantly contributes to the pathogenesis
      and progression of rodent mammary carcinoma, parallel observations for human
      breast cancer have not been concordant. In particular, the therapeutic alteration
      of somatolactogenic hormone levels has not consistently altered the course of
      human breast cancer. Recent data, however, suggest that extra-pituitary tissues
      are capable of elaborating PRL; indeed, the observation of sustained serum levels
      of PRL in post-hypophysectomy patients supports this hypothesis. Proof of an
      autocrine/paracrine loop for PRL within normal and malignant human breast tissues
      requires that the following three criteria be met: (1) PRL must be synthesized
      and secreted within mammary tissues; (2) the receptor for PRL (PRLR) must be
      present within these tissues; and, (3) proliferative responses to
      autocrine/paracrine PRL must be demonstrated. These criteria have now been
      fulfilled in several laboratories. With the demonstration of a PRL
      autocrine/paracrine loop in mammary glands, the basis for the ineffective
      treatment of human breast cancer by prior endocrine-based anti-somatolactogenic
      therapies is evident. These findings provide the precedent for novel therapeutic
      strategies aimed at interrupting the stimulation of breast cancer growth by PRL
      at both endocrine and autocrine/paracrine levels.

PMID- 10887521
TI  - Recombinant analogues of prolactin, growth hormone, and placental lactogen:
      correlations between physical structure, binding characteristics, and activity.
AB  - The availability of recombinant growth hormones, prolactins, placental lactogens
      and a few soluble extracellular domains of their receptors have extended our
      ability to study the interaction of somatogenic and lactogenic hormones with
      their receptors. Modifications of their respective cDNAs have enabled the
      preparation of sufficient amounts of the corresponding proteins. The present
      review summarizes two aspects of these interactions: (a) the relationship between
      binding, the apparent ability to dimerize the receptors and biological activities
      in vitro and in vivo; and (b) the effect of mutations on selective changes in the
      ability of human growth hormone and bovine placental lactogen to interact with
      somatogenic and lactogenic receptors. In view of this summary, strategies for
      preparing a second generation of biologically relevant recombinant hormones are
      discussed.

PMID- 10887523
TI  - Dedication. Yale J. Topper (1916-1995).

PMID- 10887522
TI  - Cleavage of prolactin by its target organs and the possible significance of this
      process.
AB  - An enzymatically cleaved form of rat prolactin (rPRL) was first described in
      1980. This cleavage produces a molecule that consists of two chains of amino
      acids linked by a disulfide bond between two Cys residues. Reduction of that bond
      produces two fragments of 6 and 16 Kd. A considerable amount of information has
      accrued in recent years about the cleaved molecule and its 16-Kd fragment. The
      enzyme that cleaves the molecule is present in target tissues of PRL in rodents
      (e.g., mammary gland and ventral prostate), and the activity of the enzyme
      changes with the functional state of the mammary gland. Rat mammary PRL-cleaving
      activity is specific for rodent PRL, and the enzyme is localized in the stroma of
      that gland. The enzyme that cleaves rPRL is probably cathepsin D, and the sites
      of cleavage on the molecule have been identified. The cleaved form of rPRL has a
      high degree of activity in various assays, but it has reduced activity in
      radioimmunoassays. The 16-Kd fragment retains a significant degree of bioactivity
      in in vitro mitogenic assays, and specific binding sites for the fragment have
      been identified. Novel bioactivities for the cleaved form of rPRL and its 16-Kd
      fragment have been reported, and these molecules may account for the fact that
      bioassay estimates of PRL in rat serum are generally higher than are RIA
      measurements. Although the 16-Kd fragment has significant bioactivity, it
      contains only six of the fourteen residues that are thought to participate in the
      coupling of the intact hormone to its receptor. Cleaved rPRL is present in rat
      serum (but not in milk), but whether the 16-Kd fragment is formed in vivo has not
      yet been determined.

PMID- 10887525
TI  - The impact of new technology on infectious diseases.

PMID- 10887524
TI  - [The yin yang of inflammation: inducible and constitutive cyclooxygenase.
      Nimesulide and selective inhibitors of inducible cyclooxygenase].

PMID- 10887526
TI  - Who should be screened for hereditary breast cancer and what should be done with
      the information?

PMID- 10887527
TI  - [Chemoprevention of breast cancer. Impact of a new therapeutic strategy].

PMID- 10887528
TI  - Genetics in adult polycystic kidney disease: how far can we go?

PMID- 10887529
TI  - [What is new in medical imaging?].

PMID- 10887530
TI  - Apolipoprotein E genotyping for Alzheimer's disease: ethical concerns and
      implications for clinical practice.

PMID- 10887531
TI  - [New technologies and interventions in neonatology].

PMID- 10887532
TI  - The impact of new technologies on health. Saliva as a valuable diagnostic tool.
      Minireview.

PMID- 10887533
TI  - [Sudden death. Implantable defibrillators. Value of the technology and economic
      impact].

PMID- 10887534
TI  - The ethics of applying new technologies: lessons from minimally invasive surgery.

PMID- 10887535
TI  - Death of the stethoscope.

PMID- 10887536
TI  - [Multicenter study of children with terminal renal failure in Lebanon].
AB  - A retrospective study was conducted in June 1997 concerning all Lebanese children
      with end stage renal failure. This study was able to recognize 20 children and
      infants (age less than 15) dialysed regularly in 8 hemodialysis centers. The
      other 23 centers are not following children. Thirteen children are dialysed on
      bicarbonate and seven on acetate. Children receive erythropoietin occasionally;
      30% of them are polytransfused, 60% of them suffer from anemia. Four children
      have never received immunization against hepatitis B and three are seropositive
      for hepatitis C. None of these children has regular school attendance and
      psychological support for the child and his family do not exist. We conclude that
      the situation of children on hemodialysis in Lebanon is alarming. Solutions are
      possible and available; they need to be undertaken urgently.

PMID- 10887537
TI  - [Simultaneous bilateral spontaneous rupture of the quadriceps tendon. Apropos of
      a case of a hemodialysis patient with hyperparathyroidism and review of the
      literature].
AB  - The bilateral simultaneous spontaneous rupture of the quadriceps tendons is a
      rare condition. Of the pathologies associated with this condition, in the
      literature, chronic renal failure with hyperparathyroidism is of special
      interest. In this context, the frequency of this lesion is related to the
      chronicity of the renal disease. We report a case treated surgically with a good
      functional result in a patient under dialysis with hyperparathyroidism.

PMID- 10887538
TI  - Dilemma of oxalosis in end stage renal failure: isolated kidney allograft or
      hemodialysis.
AB  - We report the case of a 10-year-old girl who received a cadaveric kidney
      transplant for oxalosis after a period of 12 months on hemodialysis. The donor
      was a 6-year-old child. Cold ischemia was four hours. Diuresis occurred
      immediately in the operating room. Mean daily diuresis was maintained at 8
      liters: first by i.v. perfusion, then by nocturnal continuous nasogastric
      hydration. In addition to the usual immunosuppressive drugs, she received
      pyridoxine, sodium citrate, phosphate, hydrochlorothiazide and magnesium. Daily
      hemodialysis was performed from Day 1 to Day 9 and four additional sessions every
      other day. The postoperative course was satisfactory. Oxaluria was elevated
      initially at 1074 mg/24 h (normal < 50 mg/24 h). One year later, mean daily
      diuresis is still 8 liters, renal function is normal and oxaluria is at 296 mg/24
      h. Repeated graft sonography showed no nephrocalcinosis, but mild oxalate
      deposits are noted on renal biopsy. Isolated renal transplantation was successful
      in our patient. It allowed us to stop hemodialysis and to avoid extra-renal
      accumulation of oxalate. Despite this success, we are convinced that long term
      prognosis is uncertain and liver transplantation should be realized to correct
      definitely the biochemical defect.

PMID- 10887539
TI  - Intraabdominal panniculitis. Report of three cases and review of the literature.
AB  - Intraabdominal panniculitis is a rare, benign idiopathic disorder of the
      mesentery. Patients usually present with abdominal pain and a palpable mass. The
      cross-sectional imaging findings are characteristic and consist of a fibrofatty
      central mesenteric mass lesion encapsulating the mesenteric vessels with
      displacement of the bowel loops, that can suggest the diagnosis. Imaging is also
      important to establish a definitive diagnosis by an image-guided percutaneous
      biopsy, assess extent of the disease for selection of appropriate therapy,
      exclude associated abnormalities namely malignancies, and for follow-up.

PMID- 10887540
TI  - [Clinical research criteria for benign prostatic hyperplasia].

PMID- 10887541
TI  - [Epidemiology of benign prostatic hyperplasia. Definition of the condition].

PMID- 10887542
TI  - [Growth factors and benign prostatic hyperplasia].

PMID- 10887543
TI  - [Acute urine retention: a public health problem].

PMID- 10887544
TI  - [Benign prostatic hyperplasia: measurement of symptoms, IPSS and life quality
      assessment].

PMID- 10887545
TI  - [Cost-effectiveness of different diagnostic tests for the study of benign
      prostatic hyperplasia].

PMID- 10887546
TI  - [Benign prostatic hyperplasia: initial clinical evaluation WHO-98].

PMID- 10887547
TI  - [The clinical survey in benign prostatic hyperplasia. Where are we?].

PMID- 10887548
TI  - [Evidence based on drug therapy of benign prostatic hyperplasia].

PMID- 10887549
TI  - [Emergence of dengue hemorrhagic fever in the Americas. Reemergence of dengue].
AB  - Dengue is at present the most important human arbovirosis. It is the main cause
      of hospitalization and death among children from southeast Asia. Two fifth of the
      world population live in dengue risk areas. In 1997, over 100 countries reported
      epidemic and more than 50,000,000 cases and 25,000 deaths were estomated.
      Nowadays, the Americas is passing through the same situation Asia faced years
      ago. In 1997, 27 countries reported cases of dengue, and in 14 of them cases of
      dengue hemorrhagic fever were documented. In all, 387,459 cases of classic dengue
      and 11,645 of dengue hemorrhagic fever were registered. During the last 2 decades
      dengue has increased significantly in our region with ups and downs in the annual
      incidence since 1981. It should be remarked that every 3 or 4 years there is a
      cyclic decrease and a further increase of the incidence, though it trends to
      rise. As regards dengue hemorrhagic fever, the situation is not more favorable.
      The Cuban epidemic that appeared in 1981 was completely untimely in the region.
      In 1989, 8 years later, the second important dengue hemorrhagic fever epidemic
      emerged in Venezuela, and from that moment on there has been an increasing
      tendency of this clinical form of the disease. The factors of the emergence and
      reemergence are present and rise year after year. The neoliberal policies and the
      consequent privatization of the health services in most of the countries allow us
      to watch a gloomy future in relation to the development of dengue and its severe
      form, the dengue hemorrhagic fever/dengue shock syndrome.

PMID- 10887550
TI  - [Bacterial origin of acute diarrhea in Merida, Venezuela].
AB  - 464 stool specimens from children under 5 with acute diarrheal disease and other
      149 specimens from the control group were studied from July, 1993, to May, 1995.
      The specimens were collected at the Pediatric Emergency Department of the
      Autonomous Institute of the Teaching Hospital of Los Andes, Merida, Venezuela.
      The presence of the internationally recommended bacterial, parasitary and viral
      agents was investigated. The commonest bacteria isolated as unique pathogens
      were: Shigella (42.85%), Shigella sonnei, the most found, (66.67%), and the
      thermotolerant Campylobacter, Aeromonas sp. and enteropathogenous Escherichia
      coli, with 15; 15 and 13.5%, respectively. 6.5% of parasites and 24.12% of
      Rotavirus were also found. It was concluded that in the period of time under
      study the infectious and mainly, the bacterial origin is an important cause of
      acute diarrheal disease in Merida.

PMID- 10887551
TI  - [Specific humoral response in Balb/c mice inoculated with a genome library of
      expression of Trypanosoma cruzi].
AB  - A genomic expression library of Trypanosoma cruzi (T. cruzi) was made using
      plasmid pcDNA3 as a vector, with which male mice from the Balb/c isogenic line
      were intramuscullary inoculated. It was used a positive control group that was
      administered soluble antigens of T. cruzi. Other 2 groups received genomic and
      plasmid DNA, respectively. One group was not immunized. Weekly blood samples were
      obtained from all the animals until the fourth week and 2 weeks after
      reimmunization to study the response of specific antibodies against the
      microorganism antigens by an indirect immunoenzymatic assay (ELISA). It was
      observed a significant increase of specific antibodies in the animals reimmunized
      with 50 micrograms of the library, as well as in the group immunized with soluble
      antigens of T. cruzi.

PMID- 10887552
TI  - [Comparative analysis of resistance to insecticides in strains of Culex
      quinquefasciatus, from Camaguey].
AB  - The organophosphate, carbamate and pyrethroid resistance levels in 14 strains of
      Culex quinquefasciatus from Camaguey were studied by bioassays and biochemical
      tests in larvae with or without synergists. The use of electrophoresis in
      polyacrylamide gel (PAGE) allowed to identify 8 patterns of esterases, among
      which A3A6B6, BiB6 and B1A6B6 were the most frequent. It was observed that 6
      years after the suspension of malathion, there is still resistance to this
      product. There was also cross resistance to propoxur. Detoxification mechanisms
      for deltamethryn are being developed. The most important physiological mechanisms
      were: elevated esterases in the resistance to malathion, modified AchE for
      propoxur and oxidases of multiple function for deltamethryn. In relation to the
      genic frequencies, the modified AchE mechanisms was more extended than that of
      the elevated esterases in these populations of mosquitoes of the central region
      of Cuba.

PMID- 10887553
TI  - [Obtention of monoclonal antibodies against human secretory IgA].
AB  - In order to determine the IgA levels in secretions, the authors engaged
      themselves to obtain monoclonal antibodies against this immunoglobulin and to
      show their possible utilization in the development of quantitation methods. 6
      monoclonal antibodies were obtained: one against the secretory component (SC) and
      five against the heavy-chain (HC) of IgA. IgA purified from human colostrum was
      used as immunogen (HC). The immunoglobulin isotypes (IgG2a and IgG1) were
      determined in 2 monoclonal antibodies, one against SC and the other against HC.
      Polyacrylamide gel electrophoresis was performed in the presence of sodium
      dodecyl sulphate and b-mercapto-ethanol. Immunotransference was also carried out
      to determine their specificity. Secretory IgA was detected in saliva specimens.
      The anti-SC monoclonal antibody obtained in-the laboratory of the "Pedro Kouri"
      Institute of Tropical Medicine (IPK) was compared with a commercial one (Sigma
      Chemical Co.), and a similar behaviour was observed. The monoclonal antibody
      against SC (IPK) was used to detect IgA specific to LPS ogawa in persons
      vaccinated with an attenuated strain of Vibrio cholerae. Marked differences were
      found between the levels before and after immunization. The anti-HC monoclonal
      antibody was utilized to make an ELISA-like simulated system. The detection limit
      was 9.89 ng/mL.

PMID- 10887554
TI  - [VIGILA: a tool for the epidemiologic surveillance of transmissible diseases].
AB  - It is described an instrument for the epidemiological surveillance of
      communicable diseases (VIGILA) that is based on the generalization of a
      modification of the statistical model proposed by Serfling for the prognosis of
      the endemic levels of the rates of communicable diseases in a period of 52 weeks
      (1 year). The comparison made between the observed rates and the prognosticated
      rates allows to detect unusual patterns of this indicator. The observation of
      rates over the higher limit of the prognosis interval during successive periods
      is suggested as a signal of alert. The introduction of this method in a computer
      program allows its application in the epidemiological surveillance units at the
      different levels of the health system.

PMID- 10887555
TI  - [Immunogenicity of the Heberbiovac-HB vaccine in doses of 10.5 and 2.5 micrograms
      in 6-9-year-old students].
AB  - The Heberbiovac-HB recombinant hepatitis B vaccine was administered at dosages of
      10.5 and 2.5 micrograms in 3 groups of children aged 6-9 with a vaccination
      schedule at 0, 1 and 6 months of age. The immunogenecity attained between dosages
      was compared. The seroconversion with protective titres obtained at 2 months
      varied from 88.9% with 10 micrograms to 79.4% with 2.5 micrograms, whereas at 7
      months it was higher than 98% in the 3 groups. The geometrical mean with 10 mg
      was 136.63 and 2,356.8 UI/L-1; with 5 micrograms, 77.62 and 1,958.9 UI/L-1; and
      with 2.5 micrograms, 32.15 and 376.3 UI/UL-1, at 2 and 7 months, respectively. A
      high immunogenic power of the vaccine is observed at dosages of 10 and 5
      micrograms with similar results. In spite of the fact that the dosage of 2.5
      micrograms is immunogenic, the response is not desirable. These results state the
      possibility of using a lower dosage (5 micrograms) for a low risk infantile
      population, which favors the cost-benefit.

PMID- 10887556
TI  - Identification of Aeromonas strains of clinical origin with atypical phenotypical
      profiles.
AB  - A total of 47 strains of Aereomonas isolated from patients with gastroenteritis
      was analyzed for 40 phenotypical characters and for evaluating the numeric
      taxonomy based on 27 discriminatory tests. It was proved that the clinical
      isolates showed a relative phenotypical distance and the groups of strains that
      had atypical profiles were compared with the type species by the present
      identification schemes.

PMID- 10887557
TI  - [Evaluation of the pyrazinamidase test for the detection of susceptibility of
      Mycobacterium tuberculosis to pyrazinamide].
AB  - The pyrazinamidase test was used to determine susceptibility to pyrazinamide in
      55 strains of Mycobacterium tuberculosis received at the National Laboratory of
      Reference and Research of Tuberculosis and Mycobacteria of the "Pedro Kouri"
      Institute of Tropical Medicine during the first semester of 1997. On comparing
      the results obtained with the method of proportions, it was attained a
      correlation of 83.6% of sensitivity with 16.4% of false positives. It was proved
      that the pyrazinamidase test should not replace the method of proportions.

PMID- 10887558
TI  - [Determination of the minimum inhibitory concentration of fluconazole against
      Cryptococcus neoformans].
AB  - The minimum inhibitory concentration of fluconozole was determined in 36 strains
      of Cryptococcus neoformans var. neoformans by a casitone broth microdilution
      method, taking into account that it is one of the most used antifungal agents in
      our country for the treatment of cryptococcal meningitis, the second
      opportunistic mycosis in order of frequency and that with the highest lethality
      among AIDS patients. The minimum inhibitory concentration of the studied strains
      ranged 0.125 to more than 64 micrograms/mL for a geometrical mean of 2.38
      micrograms/mL. 50% of the strains were inhibited with 4 micrograms/mL and the
      least concentration that inhibited 90% was 16 micrograms/mL. It is stressed the
      importance of continuing this type of in vitro studies to detect the appearance
      of resistance of C. neoformans to antifungal agents.

PMID- 10887559
TI  - [Diagnosis of an acute respiratory infection outbreak in children under 3 years
      of age in Santiago de Cuba].
AB  - In November, 1996, there was an outbreak of acute respiratory infection in
      children under 3 in the province of Santiago de Cuba. 7 samples of nasopharyngeal
      exudates were received to determine the causal agent of the outbreak by indirect
      immunofluorescence technique (4 positive samples, 57.14%). They were inoculated
      in MDCK cells culture and those cases that presented positive hemadsorption (6
      isolates, 85.71%) were analyzed by indirect immunofluorescence techniques (6
      positive samples, 100%) and immunoperoxidase (5 positive samples, 83.3%). All the
      positive samples were classified as influenza A (subtype H3N2) which confirms
      what is reported in literature in relation to the circulation of this virus
      during that year at the national and international level. This paper allowed to
      know the causal agent of the studied outbreak of acute respiratory infection and
      to determine the circulation of the influenza A subtype H3N2 in that province.

PMID- 10887560
TI  - [Serologic diagnosis of human leptospirosis with 3 variants of the passive
      hemagglutination technique].
AB  - A serological study was conducted to evaluate 3 variants of the positive
      hemagglutination technique (HA) with the use of formalized erythrocytes of fresh
      lamb (HC) and of formalized Type O, Rh-negative human red blood cells (HH). No
      significant statistical difference were found between the results of HA and HC
      and between HC and HH. Unspecific reaction was only observed in 2 of the 200 sera
      studied by HH and HC. Heterophil antibodies were just observed in 2.5% of the
      sera studied by HH, and in 100% of the sera studied by HC. The qualitative
      parameters were determined for the variants used, and this way the repetition and
      reproducibility of the most useful variant was evaluated.

PMID- 10887561
TI  - [Evaluation of RPR-antigen developed by the Empresa de Productos Biologicos
      "Carlos J. Finlay"].

PMID- 10887562
TI  - [Leishmaniasis outbreak in Cancha Larga, Chaco, Argentina].
AB  - A leishmanioasis outbreak is reported among the inhabitants of an endemic area
      for this disease located in Cancha Larga, Chaco in Argentina. Frotis and biopsy
      confirmed that 11.8% of the whole population was affected. They were all treated
      with meglumine antimonate.

PMID- 10887563
TI  - [Hematophagic activity of and environmental effect on the main malaria vector in
      Cuba: Anopheles albimanus].
AB  - An ecological study of Anopheles (N) albimanus in a suburban population of
      Camaguey province was carried out using a human bait in two trap points (indoor
      and outdoor). A higher quantity of females in the rainy season was observed
      together with a marked exophagic trend with peak activity in the early hours of
      the evening outdoor and in the early hours of the morning indoor. The abiotic
      influence on the fluctuation of the anophele population in both trap station was
      proved.

PMID- 10887564
TI  - [Ecologic indexes in the surveillance system of Aedes aegypti (Diptera:
      Culicidae) in Cuba].
AB  - The ecological indexes called diversity (H') and equitability (J') of the
      mosquito species were determined in six of the most common reservoirs of the
      urban ecosystem in the Plaza de la Revolucion municipality, City of Havana. Data
      analysis showed that according to the values of these indexes, the most dangerous
      reservoirs were tyres, larvitraps and artificial reservoirs in general. Reference
      is also made on the use of larvitraps in the surveillance system of Aedes aegypti
      and the detection and stabilization of mosquitoes such as Aedes mediovittatus and
      Culex migripalpus in the urban ecosystem. The variety of species ranged from 2 to
      7 in the studied reservoirs which showed differences in the patterns of use of
      the resources in the urban ecosystem.

PMID- 10887565
TI  - [Levels of insecticide resistance and its mechanisms in a strain of Aedes aegypti
      of Santiago de Cuba].
AB  - As a result of the most recent dengue outbreak in Santiago de Cuba province, a
      strain of this vector was studied to determine the levels of sensitivity and/or
      resistance to organophosphate and pyrethoid insecticides. The results of
      bioassays showed low levels of resistance to fention, malathion and deltametrine,
      moderate levels of resistance to temephos, metyl-pirimifos and cipermetrine and
      high levels of resistance to chlorpirifios. According to the results obtained
      from the use of S.S.S. phosphotrithiate trybutil synergist, it was shown that
      esterases play an important role in resistance to temephos and chlorpirifos.
      Piperonyl butoxide synergist disclosed that multifunction oxidases were not
      involved in the resistance to any of the evaluated insecticides. Biochemical
      techniques were applied to detect esterase-, glutathione-S-transferase- and
      acetylcholineaterase-mediated resistance mechanisms of Aedes aegypti. In
      accordance with the high frequency values observed in each of the mechanisms, it
      was proved that esterases and glutathione-S-transferase were involved in the
      insecticide resistance but acetylcholinesterases were not. However,
      acetylcholinesterase gen was found in Aedes aegypti for the first time though at
      low frequency. The polyacrylamide-gel electrophoresis made it possible to observe
      a well-stained band with a relative mobility value of 0.779; this band was called
      A4 it was not observed in the reference strain and may be associated to
      organophosphate resistance which remains to be proved in future research.

PMID- 10887566
TI  - [Characterization of resistance to organophosphate insecticides, carbamates, and
      pyrethroids in Culex quinquefasciatus from the State of Miranda, Venezuela].
AB  - Resistance of Culex quinquefasciatus from Miranda, Venezuela to the
      organophosphate insecticides malathion and chlorpirifos was higher than 30x
      whereas resistance to pyrethroids metylpirimifos, fention, cipametrine,
      deltametrine, permetrine and lambdacyalotrine and to organochlorate DDT was lower
      than 4x. Resistance mechanisms were analyzed with piperonyl butoxide synergist
      (multifunction oxidases) and S.S.S. phosphotrithiate tributyl (DEF, esterase
      inhibitor). Multifunction oxidases did not play a significant role in resistance
      to organophosphate insecticides and carbamate; however, esterases were only
      mechanisms of resistance to malathion and chlorpirifos. The only insecticide
      affected by DEF and PB was cipermetrine. Biochemical tests revealed a very low
      frequency of the altered acetylcholinesterase mechanism (0.13). Esterase
      frequencies were high (1). Electrophoresis exposed the B1, A6 and B6 esterase
      phenotypes.

PMID- 10887567
TI  - [Assessment of the cellular immune response induced in Balb/C mice with dengue
      virus 2 envelope protein].
AB  - The cellular immune response to dengue type 2 virus envelope protein was studied.
      To this end, the lympho-proliferative capacity of T-lymphocytes obtained from
      splenocytes of animals immunized with the protein when they were stimulated by
      such protein and dengue 2 virus. It was realized that splenocytes proliferated
      significantly in response to both types of viral antigens and that the values of
      stimulation indexes were higher in response to the whole virus than to the
      protein alone. Based on the above-mentioned, it was concludes that purified
      dengue 2 virus envelope protein was capable of generating specific and memory
      responses of antigen T-cell to dengue 2 type virus.

PMID- 10887568
TI  - [Validation of an ELISA for the measurement of human IgG against serogroup B
      Neisseria meningitidis protein].
AB  - An indirect ELISA test was optimised in which B meningoccocus outer membrane
      proteins included in the Cuban Vaccine known as VA-MENGOC-BC were used as capture
      antigents. Specific antibodies in serum samples from vaccinated individuals were
      detected using a human anti-IgG conjugate, i.e. alklayne phosphatase, thus the
      reaction developed with a specific substrate called p-nitrophenilphophate.
      Standard serum was obtained from a reference standard, the gage curve range was
      625 to 20,000/mL. The control serum was selected from the most interesting areas
      for the samples, hence, assay characteristics were determined. Intra-assay, inter
      assay and total inaccuracies were lower than 10% in the most linear area of the
      curve. Detectability was 700/mL. Recovery, paralelism and linearity studies
      showed an under 10% inaccuracy.

PMID- 10887569
TI  - [Analysis of fatty acids from strains of Mycobacterium habana and Mycobacterium
      simiae].
AB  - A comparative analysis of mycobacterial fatty acid fractions of Mycobacteriun
      habana and Mycobacterium sineae strains was made. This study used the gas-liquid
      chromatography coupled with mass spectrometry. Chromatographic profiles obtained
      from this technique were exposed and compared. This technique proves to be
      valuable as an alternative element in mycobacterial characterization and makes it
      possible to analyze the possible differences that may exist among mycobacterial
      species and to identify the present fatty acid fractions. The outcome proved that
      the studied strains had quantifiable quantities of over 20 C atom chain fatty
      acids. There are small differences among the strains in terms of these organic
      components. It was confirmed that each of then describes a characteristic
      chromatographic pattern although the composition of present fatty acids is very
      similar in both studied species.

PMID- 10887570
TI  - [Antimicrobial susceptibility of Neisseria gonorrhoeae strains determined by disk
      diffusion].
AB  - The Gonoccocus Laboratory of "Pedro Kouri" Tropical Medicine Institute carried
      out a study of in vitro susceptibility of Neisseria gonorrhoeae to penicillin,
      tetracycline, cefuroxime ceftriaxone, cefotaxine and ciprofoxacin by means of a
      disk diffusion method with the culture medium agar base GC plus supplement. In
      the first phase, the method was standardized and the reference N. gonorrhoeae
      ATCC 49226 strain was used whereas in the second phase, 50 gonococcal strains
      isolated in 8 provinces during 1995 and 1996 were examined. The results of such
      standardization confirmed that the antimicrobial susceptibility values were
      within the allowable limits. 52 and 34% of strains were resistant to penicillin
      and tetracycline respectively and all of them showed susceptibility to the rest
      of evaluated antimicrobial drugs. We recommend the use of the disk diffusion
      method for surveillance of gonococci resistance to these drugs in our country.

PMID- 10887571
TI  - [Survey on risky sexual behavior and sexually transmitted diseases among
      adolescent students from Havana City, 1996].
AB  - The observed increase of sexually transmitted diseases (STD) in Cuba aroused the
      interest of carrying out a study aimed at exploring risky sexual behaviours and
      attitudes, and histories of STD. A crosswise descriptive study was undertaken
      using a randomized sample taken from the universe of adolescent students in the
      City of Havana during 1995-96 school year. The sample was made up by 2,793
      teenagers aged 11-19 years (1,370 females and 1,423 males). Previously trained
      experts linked to this field collected data by means of a structured interview
      which had been drawn up for this end. It was confirmed that more than half of
      adolescent students did not use condom in their sexual intercourse 57% had more
      than one sexual partner along the year, 40% believed it was difficult to keep
      only one partner whereas 35% had more than one sexual partner at the same time.
      Risk and protected sexual habits were noticed, with 39% for oral-genital and
      21.4% for genital-anal. 22% for the interviewed adolescent said they had
      histories of STD.

PMID- 10887572
TI  - [Report of a case of purulent rhinitis caused by Streptococcus pneumoniae in a
      patient with HIV/AIDS].
AB  - This paper reports a case of acute purulent rhinitis caused by Streptococcus
      pneumoniae in a HIV/AIDS patient seen at the Hospitalization Center of "Pedro
      Kouri" Tropical Medicine Institute. The clinical findings were fever, severe
      purulent rhinorrea and affected general condition. Streptococcus pneumoniae was
      isolated with standard and advanced diagnosis techniques. Antimicrobial
      sensitivity test revealed that it was sensitive to cefaloridien, ampicillin,
      penicillin G and oxacillin. The patient was treated with a dose of 2 g of
      ampicillin daily for 10 days. The clinical picture of the patient improved and
      there was a total remission of the symptoms.

PMID- 10887573
TI  - [Mycobacteriosis caused by Mycobacterium gordonae. First case reported in Cuba].
AB  - Since 1990, repeated samples of a positive HIV patient were studied, who had skin
      lesions with ulcers and scabs, dirty bottom and prominent edges; hyperergic
      Mantoux and very low CD levels. As a result, a slowly growing pigmented strain
      was isolated and classified as Mycobacterium gordonae by using standard as well
      as alternative bacteriological studies such as the mycobacterial mycolic acid
      analysis. The patient was treated with 4 antibacilar drugs and 6 weeks after the
      starting of the treatment, all reported skin lesions had disappeared.

PMID- 10887574
TI  - [Assessment of an ELISA for the detection of antibodies against HIV-1 protein
      p24].
AB  - DAVIH AC p24 kit for detecting anti p24 antibodies of HIV-1, worked out by the
      National Laboratory of Reference of AIDS (Labor-1, Cuba) is assessed and results
      are compared to those of the Western Blot technique (DAVIH-Blot, Labor-1, Cuba).
      191 samples from HIV positive patients at various stages of the disease were
      analyzed. 96% sensitivity; 100% specificity and 96.3% coincidence were found in
      both techniques. The anti p-24 ELISA-DAVIH system is a good alternative for the
      follow-up of HIV positive patients.

PMID- 10887575
TI  - [First report of Neisseria polysaccharea in Cuba].
AB  - The National Laboratory of Reference of Pathogenic Neisserias of "Pedro Kouri"
      Tropical Medicine Institute studied 58 strains which had been previously
      identified as Neisseria meningiditis and isolated from nasopharyngeal carriers
      from 1985-1998. They were applied the knapp detection scheme plus the
      glutamiltransferase production test. The latter and the polyscharide production
      based on 5% sacarose allowed to make a differential diagnosis between N.
      meningitidis and Neisseria polyccharea. It was possible to identify a N.
      polysaccharia strain, a species that is reported for the first time in Cuba.

PMID- 10887577
TI  - [Chorioretinitis caused by toxoplasma in children].
AB  - In a period of 5 years, 21 children with ocular lesions caused by toxoplasma
      (chorioretinitis due to toxoplasma) were seen at "Pedro Kouri" Tropical Medicine
      Institute. Of the 21 children, 5 (23.8%) had lesions in both eyes and 16 (76.1%)
      in one eye (9 in the left eye and 7 in the right one). 9 children (42.8%)
      initially had active lesions that responded satisfactorily to medical treatment
      whereas 12 (57.1%) came to the hospital with healed lesions that did not require
      any treatment. They were all followed up as outpatients with favorable evolution
      in all cases.

PMID- 10887576
TI  - [Knowledge, opinions, and practices regarding Aedes aegypti].
AB  - The active participation of the community is indispensable for reducing Aedes
      aegypti mosquito populations so causes leading to their growth, actions taken,
      effects on the health and the people in charge of controlling such mosquitoes are
      all dealt with in this paper. 210 persons were interviewed from June 25 to 27,
      1997. The causes of the growth of the mosquito population were: excessive garbage
      (59%), dirty waters (58%), open water reservoirs (50%) and lack of fumigation
      (21%). 40% of interviewed people did not know that these vectors can breed even
      in clean waters. They mentioned some effects on the health due to the mosquito
      bites. 51% said that mosquitoes should be jointly controlled by the State and the
      community but 35% believed that the State should be the sole responsible for this
      task. These opinions may determine that steps are not properly taken to avoid
      proliferation of vector and that the activities of the anti-vector program are
      not really understood since they do not meet the expectations.

PMID- 10887578
TI  - [Mouth colonization by Streptococcus pyogenes in patients with impetigo].
AB  - The faucial carrying of Streptococcus pyogenes in patients presenting impetigo
      was determined as a risk factor for non-suppurative complications (acute
      glomerulonephritis). The fauces cultures of these patients revealed a S. pyogenes
      colonization of 65% and all the isolates were penicillin-sensitive. It was
      concluded that the high percent of faucial colonization made a systemic
      antimicrobial treatment necessary.

PMID- 10887579
TI  - [Determination of verotoxins in strains of Escherichia coli O157:H7].
AB  - We performed an study to find out the main virulence factor in verotoxigenic
      Escherichia coli: the production of verotoxins in 50 non sorbitol-fermenting
      Escherichia coli strains (possible enterohemorrhage) which were isolated from
      children with acute diarrheas in the City of Havana and referred to the National
      Reference Laboratory for acute diarrheal diseases in "Pedro Kouri" Institute. By
      using the agglutination technique with latex particles of E. coli O157:H7, we
      determined whether the verotoxins belonged to this serotype, we also researched
      the production of verotoxins in Vero cell culture. Ninety-six percent of the
      total number of strains were positive in the qualitative determination of this
      factor which was more frequently observed after 24 hours.

PMID- 10887580
TI  - [Standardization and evaluation of the modified vibriocidal assay].
AB  - The vibriocidal antibody test is a reliable and well-documented method to
      determine bacterial antibodies to Vibrio cholerae 01 antigens. It consists of
      mixing serum dilutions and a steady quantity of bacteria and supplement to cause
      cell lysis. Titer is determined by visual observation. In this paper, we
      implemented a change in the presented method where a pH and glucose indicator was
      added to the culture medium used to stop the reaction, which allowed a quicker
      reading by any person who are not very familiar with the carrying out of this
      test since the colour change in the plaque is quite evident.

PMID- 10887581
TI  - [Production and partial purification of the main hemolysin (pneumolysin) of
      Streptococcus pneumoniae].
AB  - The capacity of 36 Cuban strains of Streptococcus pneumoniae to produce
      pneumolysin was studied, and 94.4% of them were determined to be producers of
      that enzyme. One of the best producers was cultured at a great scale and the
      pneumolysin found in the supernatan was partially purified through an ion
      exchange chromatography in mono-Q column. This method made it possible to recover
      the enzyme whose purity level increased by 4.39 with 100% output.

PMID- 10887582
TI  - [Evaluation of a new technology for the detection of enterovirus in sewage].
AB  - This paper reported the appraisal of a novel technology for the detection of
      enterovirus in sewage based on a viral recovery method using polyethylenglycol as
      a concentrating agent and on the combined use of viral isolation and polymerase
      chain reaction as viral detection and identification techniques. It was also
      confirmed that the viral recovery method is highly efficient since it allows to
      recover all viruses present in sewage and to preserve their infective capacity.
      It was proved that the polymerase chain reaction (PCR) is less sensitive than
      cell culture for detecting enteroviruses in sewage. It is also possible to use
      guadinine isothiocyanate, whose components can be prepared in the lab, as an
      alternative method for taking out and purifying nucleic acids instead of using
      the conventional TRIZOL method which is the one recommended in these cases by the
      World Health Organization.

PMID- 10887583
TI  - [Prevalence of antibodies against herpes simplex virus, Epstein-Barr virus and
      cytomegalovirus in a group of patients after hemodialysis].
AB  - Infections from herpes virus play a key role in post-transplantation pathology,
      so it is indispensable to characterize the group of would-be renal transplant
      recipients. IgG antibody titers were detected by indirect immunofluorescence to
      Herpes simplex virus, Epstein Barr virus (EBV) and cytomegalovirus (CMV) in 100
      patients treated with hemodialysis in the Nephrology Institute. The prevalence of
      antibodies to cytomegalovirus and to Herpes simplex and Epstein Barr viruses was
      100% and 95% respectively. Average geometric titers (AGT) of antibodies to CMV
      were significantly higher. There was no correlation between AGT and sex, age,
      time of disease remission, number of blood transfusions and number of
      transplants.

PMID- 10887584
TI  - [Study of various biological properties of 3 strains of dengue 2 with differences
      in their nucleotide sequences].
AB  - Some biological properties of Dengue-2 strains such as A-15 (isolated in Cuba in
      1981); Jamaica (isolated in Jamaica in 1981) and New Guinea "C" (NG"C") standard
      strain differing in their nucleotide sequences were studied. The results showed
      that the cytopathic effect in C6/36 HT cell line occurred earlier in A-15 strain
      and that fluorescence was first detected in Jamaica and A-15 strains. This seems
      to indicate that rapid detection of strains does not have any relation to neither
      their history of passage nor the original isolation system. A-15 and NG"C"
      strains exhibited an heterogeneous pattern formed by big and small plaques but
      average size of plaques in NG"C" was lower whereas Jamaica showed only small
      plaques. The most neurovirulent strain in mice was NG"G" followed by A-15 whereas
      Jamaica was not neurovirulent at all. These results indicate that A-15 has a
      different biological behaviour which is probably due to intrinsic differences. It
      should be taken into account that 7 amino acid changes were found in the envelope
      protein which may have affected the expression of some biological properties.

PMID- 10887585
TI  - [Proportional abundance of culicidae in the urban ecosystem of Havana City].
AB  - Proportional abundance of the four most common mosquito species was determined in
      six types of breeding places located in Plaza de la Revolucion municipality, City
      of Havana from 1993-1996. Culex quinquifasciatus exhibited values over 0.60
      except in tyres and larval traps in 1993 and 1994 whereas Aedes mediovittatus
      showed similar values in low tanks and artificial reservoirs in 1994 (0.43 and
      0.56 respectively). It was also observed that this species prefers larval traps.
      Aedes aegypti and Culex migripaplpus had the lowest abundance values (0.01).
      These results allowed us to state that there is a sort of shared use by these
      species of those reservoirs where they breed and that Culex quinquefasciatus is
      the predominant one.

PMID- 10887586
TI  - [Assessment of the impact of the biological rodenticide Biorat in populations of
      rodents settled in several crops of the Republic of Costa Rica].
AB  - The impact of biological rodenticide Biorat on populations of rodents settled in
      some crops was determined; these crops are highly infested with Sigmodon
      hispidus, a very common vector in various Central American countries. The
      trapping technique and the appraisal of damages allowed to calculate the index of
      infestation which ranged from 75 to 90 percent in three crops. Twenty for to 36
      kg of BIORAT were applied to 6 ha planted with Cucumis sativus (cucumber),
      Ipomoea batata (sweet potato) and Ananas comusus (pineapple). This action brought
      about that the rodent population in such crops reduced the potential damage and
      consequently, index of infestation was reduced by 94.6 to 98%; therefore, the
      residual population left amounted from 2 to 3.5%, meaning that damages were under
      the economic threshold. Generally speaking, the results were similar to those of
      other countries.

PMID- 10887587
TI  - [VA-MENGOC-BC vaccine: its impact on meningococcal disease in children 1-4 years
      old].
AB  - VA-MENGOC-BC vaccine has been administered to Cuban infants since 1991 through
      the National Immunization Program (NIP) so it was necessary to evaluate its
      effects on 1-4 years-old children included in the highest risk group. To this
      end, a descriptive study of the morbidity and mortality from meningococal disease
      was carried out taking the vaccine histories of 145 cases occurred from 1991 to
      1996 into account. The decreasing trend of the incidence density (ID) of
      meningococcal disease in all the age groups in the studied period was among the
      most important results, the highest decline was observed in one-year old infants
      with an ID of. 10.8 per 100,000 children/years at the end of the period. The
      percent distribution of occurrence showed a predominance of one-year old group at
      the beginning of the program. Implementation, and a change to 3-4 years old group
      at the end of the period. A high of percent of vaccinated sick children had been
      immunized against MD over one year ago (697.5 days as average). 35 children died
      during the period and the highest mortality density decline (1 per 100,000
      children a year) was observed as of 1993; 2 years-old children were at highest
      risk of death. Seventy three percent (73.1%) of those vaccinated had been
      immunized for over once year. The general lethality was 24.1%, the lowest was
      14.3% in one year old children. The changes occurred in meningococcal disease
      behaviour within this high risk group, which are attributed to the administration
      of vaccine as part of the NIP fully justifies the continuation of the application
      of this vaccine.

PMID- 10887588
TI  - [Adverse reaction surveillance system for vaccination in the Republic of Cuba].
AB  - We briefly sets forth the design of a surveillance system of adverse events as a
      part of the Vaccination Program in Cuba since it has had a world impact and thus,
      the real scope of such events can be known in the country. On the other hand,
      this system may be useful for Cuban vaccine-producing industries to prove
      innocousness of their products after these being licensed. Family physician and
      nurse program which covers 98% of the Cuban population will make the active
      passive surveillance of all those persons who had been vaccinated in a territory
      possible. This surveillance system will be able to measure risks of adverse
      events by vaccine, age, number of doses, province and municipalities and by batch
      and manufacturer so that the causes leading to those events can be known. For
      this reason, it will contribute to improve the quality of services, protect the
      vaccination quality and upgrade the Cuban surveillance system.

PMID- 10887589
TI  - [Cathepsin L-like activity in hemolymph of females crammed with Boophilus
      microplus].
AB  - The cysteine-proteinase activity present in the hemolymph of females crammed with
      Boophilus microplus at the second oviposition was proved. The enzyme assay was
      performed using the synthetic N-carbobenzoxi-phenilalanyl-arginil-4-metoxibetan++
      +-naphthylamide substrate, and hydrolysis in both raw ovarim extract and
      hemolymph were observed. The activity was 100% inhibited by trans-epoxisuscinyl-L
      leucidamide (4-guadinine) butane, an specific inhibitor for cysteine-proteinase.
      Polyacrylamide and gelatin-gel electrophoresis showed the existence of only one
      active band in both samples tested with the same electrophoretic sliding
      (approximately 38 kDa).

PMID- 10887590
TI  - [Circulating Haemophilus influenzae in Cuba. Characterization of strains isolated
      from meningitis].
AB  - Haemophilus influenzae B(Hib) is often associated with serious systemic
      infections in children under 5 years of age. Since 1993, it is the most frequent
      agent isolated in meningoencephalitis. All the strains isolated in the country
      have been characterized in the National Reference Laboratory at the "Pedro Kouri"
      Tropical Medicine Institute. Results revealed that 97% of strains isolated from
      bacterial meningoencephalitis in Cuba during the period 1993-1995 corresponded to
      serotype B, 0.6% to serotype A and 2.4 not belong to any serotype. The
      classification of serotype B-strains into biotypes proved that 76% was biotype I
      and 21% biotype II, 8 to biotype III and 1.2% was biotype V. This study found the
      following resistance to ampicillin 40%, to chloranphenicol 43.3%, sulpha
      metoxazol 36%, trimetroprim 37.3% and tetracycline 31%.

PMID- 10887591
TI  - [Infection/immunity by hepatitis B virus in an adult population of Havana City.
      Cuba 1995].
AB  - The results of a study of markers of infection/immunity by hepatitis B virus in a
      community of the health area in "Cristobal Labra" polyclinics, City of Habana in
      1995. The studied healthy adult population was not included in any vaccination
      strategy with hepatitis B vaccine. Two markers were studied: Hepatitis B surface
      antigen and its corresponding antibody (anti-HBs). HBsAg-positivity was 1.05% and
      anti-HBs positivity was 13.39%. Of anti-HBs-positive cases, 13.39% had titers
      from 10-50 UI/L and the rest (43.68%) had titers over 50 UI/L.

PMID- 10887592
TI  - [Chernobyl 13 years after: consequences for protection of populations].

PMID- 10887593
TI  - [Behavior disorders in dogs].

PMID- 10887594
TI  - [Physiopathology and etiology of epilepsy in children].
AB  - Epilepsy is an association of chronic disorders characterised by recurrence of
      paroxysmal manifestations related to synchronisation of brain neuron populations.
      The mechanism is still unknown and few clinical forms are reproduced by animal
      models. A causal cerebral lesion is identified in only one fourth of cases. The
      origin of epilepsy thus remains largely speculative, although natural and genetic
      factors, as well as lesions have been evidenced. Nevertheless, knowledge
      concerning the genes predisposing to epilepsy has opened the way to new
      treatments, and better identification of electroencephalographic changes that
      precede the onset of crises could allow surgery without resection, by
      neurophysiological treatment of epileptogenic foci.

PMID- 10887595
TI  - [Symptoms of epilepsy in the child].
AB  - Convulsions and epilepsy in the child include widely diverse disorders, ranging
      from simple and benign to complex and severe. Initially, the general practitioner
      must consider the various diagnoses in order to prescribe appropriate
      investigations and treatment (now complex and numerous), or to orient the
      diagnosis. In the case of paroxysm, the initial step is to affirm the diagnosis
      of epileptic seizure, especially on the basis of the descriptions made by the
      child and by witnesses, possibly with the aid of an EEG. The second step is to
      determine the etiology, differentiating isolated seizures occurring in a
      particular context (for example febrile convulsions) from epileptic seizures with
      no special context. The description of the seizure and the inter-critical EEG
      lead to classifying the seizure as partial or generalised and, if it is repeated,
      to consider it as composing one of the childhood epileptic syndromes.

PMID- 10887596
TI  - [Febrile convulsions and other occasional convulsions in children].
AB  - Febrile convulsions are the main etiology of the occasional convulsions. They
      occur between 6 months and 5 years. They are short, bilateral, clonic or tonico
      clonic. Febrile convulsions are classified in 2 groups: benign febrile
      convulsions and complicated febrile convulsions. When it exists, the genetic
      predisposition is a significant factor recurrent of febrile convulsions, but
      their prognosis remains good. Treatment depends on the diagnosis of simple or
      complicated febrile convulsions. The treatment of febrile convulsions is intra
      rectal diazepam (0.5 mg/kg). The risks of recurrence of convulsions are inversely
      proportional to the intensity and duration of the fever episode before the
      convulsion.

PMID- 10887597
TI  - [Idiopathic epilepsy in the child].
AB  - Study of idiopathic epilepsy in childhood can distinguish various syndromes on
      the basis of clinical and electroencephalographic criteria. There is much
      overlapping between the syndromes described. The aim of the classification is to
      define precisely the prognosis of each disorder and to approach treatment
      effectively and safely, avoiding aggravation of a condition by poorly adapted
      prescription. The main distinction is between partial seizures, among which the
      principal is centro-temporal with spikes, and generalised seizures of which the
      most common are absence epilepsy and juvenile myoclonic epilepsy. Since the
      phenotypes are well defined, molecular genetic studies should lead to better
      knowledge of the complex biochemical mechanisms of idiopathic epilepsy. Seizures
      that occur without lesions are well managed by treatment in most cases and have a
      good psychosocial prognosis. The possibility of acquiring autonomy, familial
      overprotection, restrictions and interdictions must all be kept in mind in the
      psychological, social and educational handling of persons with epilepsy, most of
      which are benign cases.

PMID- 10887598
TI  - [Symptomatic and cryptogenic epilepsies in the child].
AB  - Symptomatic and cryptogenic epilepsies are related to detected or suspected
      cerebral lesions. Early identification of defined epileptic syndromes and
      etiology is helpful to adapt treatment. Generalized epilepsies are severe, often
      refractory and generally associated with cognitive dysfunction or regression.
      Partial symptomatic or cryptogenic epilepsies represent about 40% of all
      epilepsies in childhood and diagnosis as well as therapeutic strategy can be
      difficult. Semiology of partial seizures is related to epileptogenic focus and
      discharge propagation. Causes are numerous and are to be always extensively
      searched.

PMID- 10887599
TI  - [Epileptic encephalopathies].
AB  - Epileptic encephalopathy, a major neurologic disorder, leads to upper motor
      involvement and epilepsy. Its clinical expression varies according to cerebral
      maturity and etiology. Epilepsy manifests by spasms, partial seizures or
      myoclonia in the newborn, essentially by spasms in the infant, but also by
      myoclonia or sometimes by multifocal partial seizures. In the child, epileptic
      seizures have a more varied expression: atypical loss of contact, tonic or tonic
      clonic seizures, myoclonia and sometimes status epilepticus. Inter-seizure
      electroencephalograms of patients of all ages show severe diffuse, constant
      anomalies. These epilepsies are associated with delayed development, mental
      retardation and behavioural disorders, requiring appropriate treatment as early
      as possible.

PMID- 10887600
TI  - [Treatment and followup of epilepsy in children].
AB  - The decision to treat and the choice of the right antiepileptic drug depend on
      frequency, severity, type of seizures, epileptic syndrome, familial and school
      life, impact of seizures. On the other hand it is important to know the pediatric
      characteristics of pharmacology, tolerance, possible side effects and efficacy of
      each antiepileptic drug. Some antiepileptic drugs could also worsen some types of
      seizures. Other therapies can be efficient in refractory epilepsies: steroids,
      vague nerve stimulation, ketogenic diet and surgery. Clinical informations are
      essential to appreciate drugs efficacy and safety. Physician could be very
      important for the social and school insertion of epileptic children.

PMID- 10887601
TI  - [Cognitive and socio-educational ramifications of epilepsy in the child].
AB  - Cognitive effects and psychosocial risks after childhood onset epilepsy are
      better known nowadays, as well as their dependency upon several causative
      factors. Remission of seizures does not ensure good psychosocial outcome. A
      specific prevention and evaluation work is always necessary, and is first a
      medical work. Information has a very important part. Restrictions have to be
      optimally adapted to seizure related risk, in order to obtain an improvement in
      quality of life. Neuropsychological assessments and psychopathological approach
      are both necessary. Neuropsychological assessment may show specific cognitive
      impairments related to epilepsy type and localisation or epileptic syndrome.
      Rehabilitation has to be suited to each child, taken into account his
      intellectual development as well as his behavior and relationships.
      Multidisciplinary teams working in coordination to teachers are an important
      need.

PMID- 10887602
TI  - [Fractures of the upper femur in adults. Etiology, mechanisms, diagnosis,
      outcome, treatment].

PMID- 10887603
TI  - [Functional intestinal disorders. Diagnosis and treatment].

PMID- 10887604
TI  - [Severe acute asthma. Prevention, diagnosis, and management of emergency
      situations with medication posology].

PMID- 10887605
TI  - [Headaches. Diagnostic approach].

PMID- 10887606
TI  - [Electrocardiographic semiology of atrial flutter, extrasystoles, ventricular
      tachycardia, auricular-ventricular block and bundle-branch block].

PMID- 10887607
TI  - [Bullous dermatosis in the adult. Diagnostic approach].

PMID- 10887608
TI  - [Anorexia nervosa and bulimia in adolescents. Diagnosis, principles of
      treatment].

PMID- 10887609
TI  - [Detection and diagnosis of anxiety].
AB  - Anxiety disorders are now defined by precise diagnostic criteria and their
      treatments are facilitated by the clinical and therapeutic studies undertaken
      during the past two decades with current classifications. However, their
      recognition in everyday clinical practice can be difficult because the patients
      do not always evoke their symptoms spontaneously, and the attention of the
      physician is generally attracted by other mental disorders, such as depressive
      syndromes. The high prevalence of anxiety disorders in the general population,
      and the handicap associated with severe forms, must incite to their systematic
      exploration, in order to propose specific therapeutic procedures to the patients.
      In addition to the clinical exploration of various anxiety syndromes, the
      clinician can be helped in this goal by assessment instruments, nowadays well
      validated and easily used, such as dimensional scales or structured diagnostic
      interviews.

PMID- 10887610
TI  - [From stressful life events to anxiety disorders].
AB  - Stress is usually defined on the basis of the consequences observed after a
      threatening environmental change. This type of definition is mainly attributable
      to Seyle who conceived stress reaction as a final pathway, related to numerous
      aggressions against physical or psychological integrity, and threatening
      homeostasis. On the other hand, different authors showed that aggression does not
      systematically leads to retroactive undoing, as some types of environmental
      modifications can provoke an increase of knowledge, enriching both coping style
      and adaptative processes. Life events can be considered as a neurohormonal
      activation following action, the activation process being strictly dependent on
      the suddenness and unexpectedness of the event. "Normal" (at times necessary)
      stress, allowing the adaptative and sometimes survival processes, has thus to be
      distinguished from pathological stress, which provokes suffering. Stressful life
      event is modifying the environment, and the subject has to mobilize all his
      capacity, specificity and defense style in order to cope with the new situation.
      In this view, stressful life events may provoke enrichment and reinforcement for
      some and severe anxious disorders for others. Numerous factors are involved in
      the deleterious effect of a stressful life event, explaining why the modalities
      of the answer are so dramatically variable between different subjects.

PMID- 10887611
TI  - [When and how to research anxiety disorders in children?].
AB  - From the epidemiological evidence, anxiety disorders appear frequent in childhood
      and adolescence. Because anxiety has normal adaptative forms through development,
      the identification of pathology may sometimes pose difficulty. Child and
      adolescent anxiety disorders are defined in modern classifications with
      diagnostic criteria nearby of those used for adulthood. Behavioural symptoms of
      anxiety often alert relatives or teachers of the children. This paper reviews the
      main behavioural signs found in anxiety disorders (shyness, school refusal, sleep
      disorders, somatic distress, slowness, domestic tyranny).

PMID- 10887612
TI  - [Anxiety disorders and somatic diseases].
AB  - Anxious disorders and general medical conditions are often associated both in
      general population and in primary care. Several etiopathological mechanisms may
      explain this association. Anxious disorders in medical patients are not enough
      recognized and treated. Treatment of both disorders should enable to relieve
      patient's distress, to improve his quality of life and prognosis of both
      disorders.

PMID- 10887613
TI  - [Diagnosis and management of anxiety in victims of psychological trauma].
AB  - Management of psychic injury has been developing in France recently. Community
      catastrophies like wars or natural events, individual's stress are more and more
      related. Physicians are qualified for the treatment of their psychic
      consequences. Family doctors know people and local geographic situations and are
      often the first medical managers on the scene of the disaster.

PMID- 10887614
TI  - [Anxiety medications: indications and limits].
AB  - Difficulties in anxiety treatment is emphasized by benzodiazepine misuse.
      Pathological anxiety threshold can be understood in a dimensional perspective or
      by large in philosophical considerations. Therapeutic guidelines can be defined
      on the length of disease or by a categorical and nosological approach. Actually,
      this one appear more efficient. Therapeutic choice is under other conditions such
      as length of prescription, severity of the disorder, comorbidity and individual
      features of the patient. These difficulties in anxiety disorders chemotherapy
      lead to reconsider properly the place of psychotherapy.

PMID- 10887615
TI  - [The mnemonic effects of benzodiazepines].
AB  - The amnesiac effects of benzodiazepines were used soon after their introduction
      by anaesthetists for premedication. The aim was to crase any unpleasant memories
      of surgical intervention or its preparation. Unfortunately, these amnesiac
      effects are particularly undesirable in everyday living when the subject has to
      use his memory. The widespread usage of benzodiazepine anxiolytics for neurotic
      patients or depressives treated as out-patients, or treating sleeping problems,
      has led to a real problem of public health. Therefore, it is important to carry
      out trials with a strict methodology to understand the cognitive effects of these
      drugs, based on the application of the concepts and methods of the cognitive
      sciences (a field of rapid development in recent years). Whereas the amnesiac
      effects of benzodiazepines were ignored by physicians for years, their
      consequences are possibly overestimated at present, sometimes leading to a
      caricatural attitude in the usage of these products.

PMID- 10887616
TI  - [When and how to stop anxiolytic drugs].
AB  - The anxiolytics withdrawal constitutes a frequently desirable therapeutic
      situation in which it is necessary to integrate clinical data related to the
      disorder for which they were prescribed as well as the pharmacological and
      psychological aspects. Personality features and emotional environment of the
      patient are to be considered. This withdrawal follows a first step in which the
      anxiolytics were initially prescribed. This situation happens in medicine in
      multiple clinical situations. However, because of the phenomena of tolerance and
      dependence but also according to the efficacy of the anti-depressants in most
      anxiety disorders, benzodiazepines are described in France as over-prescribed
      molecules. General rules of prescription are a prelude to a good withdrawal
      process. This last must always be prevented especially when the dosage is high
      occurring after a long duration treatment. A good guideline for the initial
      prescription is a good ticket to anticipate the withdrawal time.

PMID- 10887617
TI  - [Psychotherapy and education of anxious patients].
AB  - Psychotherapy and education are and main component of the management of anxious
      patient. Psychoanalysis and cognitive behaviour therapies are the most indicate
      in anxiety. Because of the formation and the time required by their practice,
      they are a specialist field. A formation may be an help for the practitioner in
      the daily practice. Psychological care of anxiety is an important objective of
      public health to reduce the medical and social cost of this affection.

PMID- 10887618
TI  - [Medico-socio-economic aspects of mental health: impact of anxiety disorders].
AB  - Budgetary control policies implemented in order to cope with the increase in
      health costs in industrialised countries, all along with the inbalance of the
      national health insurance accounts, give rise to the problem of preserving the
      quality of care and quality of life of the patients. This is particularly true
      for the treatment of psychiatric diseases, and especially anxiety. Early optimal
      treatment, of adequate duration, of the anxiety disorders might be the most
      economic attitude in the management of this pathology. On the other hand, the
      impact of the treatment of anxiety on the quality of life of the patient has a
      direct effect on costs if one considers the supplement to medical consumption and
      the social deficit induced by therapeutic failure in particular anxiety
      disorders. It remains that the evaluation of the health economics of anxiety is
      difficult, because of the complexity of the parameters involved.

PMID- 10887619
TI  - Macrolide treatment decreased the size of nasal polyps and IL-8 levels in nasal
      lavage.
AB  - Recently, epidemiologic and experimental studies have been reported that long
      term macrolides are effective for the treatment of chronic airway inflammatory
      diseases including diffuse panbronchiolitis, chronic rhinosinusitis, and cystic
      fibrosis (Jaffe A, Francis J, Rosenthal M, et al. Long-term azithromycin may
      improve lung function in children with cystic fibrosis. Lancet 351:420, 1998),
      and that macrolides can directly reduce the production of IL-8 by nasal
      epithelial cells (Suzuki H, Shimomura A, Ikeda K, et al. Inhibitory effect of
      macrolides on interleukin-8 secretion from cultured human nasal epithelial cells.
      Laryngoscope 107:1661-1666, 1997). In this study we administered macrolides with
      14-membered rings to patients with nasal polyps due to chronic rhinosinusitis for
      at least 3 months and measured the IL-8 level in nasal lavage from those
      patients. The IL-8 levels in nasal lavage from patients with nasal polyps were
      reduced during macrolide treatment. There was significant correlation between
      decreased IL-8 levels in nasal lavage and the clinical effect of macrolides on
      the size of the nasal polyps. In the group whose polyps were reduced in size, the
      IL-8 levels dramatically decreased from 231.2 pg/mL to 44.0 pg/mL (p < 0.05), and
      were significantly higher before macrolide treatment than those in the group
      whose polyps showed no change (p < 0.005). This reduction in IL-8 may be an
      important aspect of the effect of macrolide treatment on nasal polyps in chronic
      rhinosinusitis.

PMID- 10887620
TI  - Allergic fungal sinusitis: a four-year follow-up.
AB  - Allergic fungal sinusitis (AFS), first described over 18 years ago and
      subsequently identified using established criteria, remains a challenge to treat.
      Our protocol has included complete functional endoscopic sinus surgery to remove
      the fungal load and restore physiologic mucous clearance. The patient is treated
      with prednisone for several months and followed monthly with total serum IgE
      levels and an established endoscopic mucosal staging system. A group of 11
      patients first treated in 1994 and presented at the 1995 American Rhinology
      Society Spring meeting are being presented again to provide an update on their
      progress over the past four years. A great deal of experience has been gained
      from their treatment and has continued to modify our postoperative medical
      management. An overview of AFS, our evolving and current treatment protocol, and
      possible future trends are discussed in this paper.

PMID- 10887621
TI  - Nasal and sinus manifestations of sarcoidosis.
AB  - Nasal and sinus diseases are considered uncommon manifestations of sarcoidosis.
      We evaluated 159 consecutive patients with sarcoidosis for nasal symptoms. Sixty
      three patients (39%) denied any nasal symptoms. Thirty-six patients (23%) had
      intermittent symptoms that lasted less than three weeks and required continuous
      intervention with nasal steroids or normal saline. Sixty patients (38%) were
      treated with nasal steroids and antibiotics for symptoms that lasted more than
      three weeks. Thirty-three patients (21%) had resolution of their symptoms after
      treatment with nasal steroids and antibiotics. Twenty-seven patients (17%) had
      symptoms that were unresponsive to three weeks of oral antibiotics and nasal
      steroids, and underwent CT scan. Based on the CT results, five patients underwent
      biopsy, which confirmed sarcoidosis. An additional patient who had a normal CT
      scan underwent a biopsy that was consistent with sarcoidosis. A retrospective
      review of 733 sarcoidosis patients was then performed, and an additional 12
      patients were identified with biopsy-proven sarcoidosis. All of these patients
      required long-term therapy with prednisone (14 patients), methotrexate (13
      patients), and/or azathioprine (8 patients). Our clinical study reveals a higher
      incidence of nasal and sinus disease in patients with sarcoidosis than has
      previously been described, and the recalcitrance of sarcoidosis when there is
      sinus involvement.

PMID- 10887622
TI  - Expression of mucin genes in chronic ethmoiditis.
AB  - We have investigated the profiles of MUC genes expressed in chronic ethmoiditis
      mucosa and normal ethmoid mucosa using RT-PCR, and the morphology of chronic
      ethmoiditis by a combination of light and electron microscope was observed. In
      the light- and electron-microscopic studies, chronic ethmoiditis mucosa revealed
      increased numbers of goblet cells with higher production of mucus in comparison
      to normal ethmoid mucosa. RT-PCR of cDNAs from three normal ethmoid mucosa
      revealed the same pattern of mucin gene expression, such as MUC5AC and MUC8.
      However, RT-PCR of cDNAs from eight chronic ethmoiditis mucosa showed the
      expression of two MUC1, six MUC4, eight MUC5AC, five MUC5B, seven MUC7, and eight
      MUC8. MUC2 and MUC6 were not detected. These results suggest that MUC4, MUC5AC,
      MUC5B, MUC7, and MUC8 are major mucins in the ethmoid mucosa and are up-regulated
      by chronic inflammation.

PMID- 10887623
TI  - Nasal cycle in patients with septal deviation: evaluation by acoustic rhinometry.
AB  - The nasal cycle in patients with septal deviation was studied by acoustic
      rhinometric techniques. This study included 24 patients with anteriorly located
      septal deviations (mean age = 23.5), and 26 normal controls (mean age = 24.7).
      Data of MCA (minimum cross-sectional area) and NV (nasal volume), collected in 20
      minute intervals, were plotted for each subject during 8 hours. Twenty of 24
      patients (83%) with septal deviation and 20 of 26 normal subjects (77%) showed at
      least one complete cycle. Duration of the nasal cycle, which ranged from 100
      minutes to 400 minutes, had no statistical difference between the septal
      deviation group (mean duration of 216 minutes) and the normal control group (mean
      duration of 227 minutes). The degrees of variation of MCA and NV, defined as
      Degree of Variation of MCA (%) = 100 (MCAmax - MCAmin)/MCAmax, Degree of
      Variation of NV (%) = 100 (NVmax - NVmin)/NVmax, which represent the percent
      change of MCA and NV throughout the study, showed no difference between the wide
      side and the narrow side, or between the septal deviation group and the normal
      control group. These findings suggest that the nasal cycle is relatively
      independent of peripheral anatomic factors for its generation. However, the
      amplitude of changes of MCA was greater in the wide side, and the sum of both
      MCAs tended to fluctuate in accordance with the fluctuation of MCA of the wide
      side. Thus, the nasal cycle seemed to be affected by septal deviation.

PMID- 10887624
TI  - Septal deviation and chronic sinus disease.
AB  - The introduction of computerized tomography in the identification of sinonasal
      pathology and associated anatomic variants has contributed to a greater
      understanding of the factors leading to ostiomeatal complex (OMC) obstruction and
      chronic sinus disease. The OMC and paranasal sinus regions were prospectively
      evaluated in 150 consecutive patients as a function of the degree of nasal septal
      deviation and compared with matched controls. These data were correlated with
      paranasal sinus disease, lateral nasal wall findings, and middle turbinate
      abnormalities. An increased incidence and severity of bilateral chronic sinus
      disease was present with increasing septal deviations (p < 0.05). Similarly,
      patients with increasing nasal septum deviations were noted to have a higher
      incidence of OMC obstruction (p < 0.05). Ostiomeatal complex obstruction in the
      direction of septal angulation was associated with nasal septal deformity;
      however, contralateral OMC obstruction was associated with middle turbinate and
      lateral nasal wall abnormalities (p < 0.05). The evaluation of the degree of
      septal angulation has helped better understand the factors contributing to
      chronic sinus disease and OMC obstruction.

PMID- 10887625
TI  - Pneumatization of the sphenoid sinus in children evaluated by magnetic resonance
      imaging.
AB  - Previous studies concerned with the normal development of the sphenoid sinus have
      reported that the onset of initial pneumatization varies from 6 months to 4 years
      of life, and that the pneumatization is completed by 12 to 14 years of age. This
      study was designed to evaluate the age-related development of the sphenoid sinus
      pneumatization in children using magnetic resonance (MR) imaging technique. MR
      images of the sphenoid sinus in 152 children, ages 2 months to 163 months, were
      retrospectively reviewed. The degree of pneumatization was classified into four
      grades as 0, 1, 2, and 3 in axial images, and into five grades as 0, 1, 2, 3, and
      4 in sagittal images. The numbers of grades were age-matched in the studied
      children. The pneumatized sphenoid sinus was identifiable as early as 2 months of
      age on axial image, and 4 months on sagittal image. Pneumatized sphenoid sinuses
      were identified in 100% of the subjects studied at the age of 3 years on axial
      image, and 6 years on sagittal image. All the children over 9 years old showed
      pneumatization of grade 2 or more both on axial and sagittal images. The results
      of this study may indicate that the sphenoid sinus begins and completes
      pneumatization earlier than previously described.

PMID- 10887626
TI  - Endoscopic and electroporation therapy of paranasal sinus tumors.
AB  - The purpose of this article is to introduce the concept of endoscopic and
      electroporation therapy for the treatment of sinonasal carcinomas.
      Electroporation therapy is a technique that combines intralesional injection of
      bleomycin combined with application of high-voltage square wave electrical
      impulse into the tumor. A transient increase in cell membrane permeability allows
      intracellular entry of bleomycin, with subsequent cytotoxicity. Two cases of
      sinonasal cancer were treated with this technique. One patient had complete
      response and is free of disease at 20 months. The other had partial response with
      control of the disease up to a year. Endoscopic electroporation therapy is
      potentially a minimally invasive method for the treatment of sinonasal
      malignancies in an experimental setting where other treatment options do not
      exist. Phase II/III national clinical trials have been initiated to study the
      efficacy of electroporation therapy.

PMID- 10887627
TI  - Middle turbinate resection: issues and controversies.
AB  - Diversity of opinion continues to exist among otolaryngologists regarding the
      potential benefits of preservation or resection of the middle turbinate during
      endoscopic ethmoidectomy. Rhinologists in favor of middle turbinate preservation
      cite the potential loss of olfactory function as well as diminished
      humidification and filtration of inspired air following its resection. In
      addition, the middle turbinate remnant could lateralize, causing frontal recess
      obstruction and frontal sinusitis. In general, it is accepted that a diseased or
      flail middle turbinate should be resected during ethmoidectomy to create a
      marsupialized surgical bed. However, in the case of a structurally sound middle
      turbinate, indications for resection vary significantly. We are reporting on 100
      primary endoscopic ethmoidectomies for chronic rhinosinusitis followed for at
      least 2 years. Of these 100 sides, 50 included conservative partial middle
      turbinectomy and 50 were performed with middle turbinate preservation. The
      postoperative clinical and endoscopic findings revealed no difference in the
      incidence of frontal sinusitis or frontal recess stenosis between groups. We
      compared additional data and present our technique of conservative middle
      turbinate resection, which preserves a portion of this structure as an important
      anatomic landmark.

PMID- 10887628
TI  - Bivalved palatal transposition flaps for the correction of acquired
      nasopharyngeal stenosis.
AB  - Nasopharyngeal stenosis is almost universally an iatrogenic problem resulting
      from surgical trauma after adenotonsillectomy or uvulopalatopharyngoplasty
      (UPPP). In addition, laser-assisted uvulopalatopharyngoplasty for the treatment
      of snoring may lead to the development of cicatricial scarring and stenosis at
      the level of the velopharynx. The most common mechanisms implicated in the
      development of acquired nasopharyngeal stenosis are the overzealous removal of
      inferolateral adenoid tissue and excessive excision of the palatopharyngeal
      arches. Symptoms generally relate to a disturbance in respiration, olfaction,
      voice quality, and deglutition, and are often poorly tolerated. Surgical options
      for the correction of this challenging problem include steroid injections, scar
      lysis, skin grafts, Z-plasty repair, and the use of various local mucosal flaps.
      We report the successful use of bivalved palatal transposition flaps performed
      through the transoral route for the correction of severe acquired nasopharyngeal
      stenosis following UPPP in two patients. Both patients developed delayed
      nasopharyngeal stenosis following their initial surgery and subsequently failed
      several attempts at surgical correction of the stenosis, including laser lysis of
      the scarred soft palate. Using this technique of repair, both patients achieved
      satisfactory resolution of their symptoms, including comfortable nasal breathing
      and normal speech. We have found that this is a simple and effective technique
      for the correction of severe nasopharyngeal stenosis.

PMID- 10887629
TI  - Topical application of mitomycin-C in endoscopic dacryocystorhinostomy.
AB  - Endoscopic dacryocystorhinostomy (DCR) is a well-established alternative to
      external DCR for treatment of obstruction of the lacrimal pathway and has a
      success rate of up to 95% in primary cases. Despite the benefits of using an
      endoscopic approach, including enhanced intranasal access to the lacrimal
      drainage system, there still exists a significant failure rate, particularly in
      revision procedures. As these failures are mainly due to obstructive
      postoperative adhesions, intraoperative adjuncts that prevent or minimize
      scarring should enhance the success rate. Endoscopic DCR was performed with
      intraoperative topical application of mitomycin-C, an antimetabolite often used
      in ophthalmologic procedures to reduce scarring and formation of adhesions
      following surgery. The procedure was successful in 7 of 8 instances, with a
      follow-up of 3 to 27 months. In one procedure, obstruction recurred 10 weeks
      after surgery. We feel that the results of this small series are encouraging and
      that further studies are warranted to determine the effectiveness of mitomycin-C
      as an adjunct to endoscopic DCR.

PMID- 10887630
TI  - On newer treatments for lymphoma.

PMID- 10887631
TI  - Support for 'minority report' on mammography for women in their 40s.

PMID- 10887632
TI  - Oral therapy for colorectal cancer: how to choose.
AB  - Either alone or in combination with other antineoplastics, fluorouracil (5-FU)
      has been the mainstay of treatment of gastrointestinal, breast, and head and neck
      cancers for the past 40 years. Numerous active 5-FU schedules are in clinical
      use, but erratic oral bioavailability has historically mandated intravenous
      administration. Recently, two methods have been used to overcome the poor oral
      bioavailability of 5-FU. The first involves the use of prodrugs that are absorbed
      intact in the gastrointestinal tract and are ultimately converted to 5-FU in
      normal or tumor tissues. An alternate approach involves the inhibition of
      gastrointestinal degradation via coadministration of an inhibitor of
      dihydropyrimidine dehydrogenase, the rate-limiting enzyme in 5-FU catabolism. The
      oral fluoropyrimidines currently in development result in prolonged exposure to 5
      FU and, therefore, have the potential to achieve clinical benefits similar to
      those seen with protracted intravenous infusions of 5-FU, but without the cost,
      complications, and inconvenience of ambulatory infusion pumps. This review
      describes several oral fluoropyrimidine regimens with activity in colorectal
      cancer: capecitabine (Xeloda), tegafur, UFT, S-1, and eniluracil plus 5-FU. An
      understanding of the distinct mechanisms of action and toxicity patterns of each
      regimen may ultimately guide treatment selection when multiple choices become
      available.

PMID- 10887633
TI  - Leuprolide implant approved for once-yearly palliative treatment of advanced
      prostate cancer.

PMID- 10887634
TI  - Surgical treatment of metastatic pulmonary soft-tissue sarcoma.
AB  - The lung is the most frequent site of metastasis from soft-tissue sarcomas. Due
      to the relative resistance of sarcoma to either chemotherapy or radiotherapy,
      compared to other solid tumors, surgical management of pulmonary metastases has
      been a pivotal therapy in this disease. With decades of experience in numerous
      centers, criteria for patient selection have been ascertained and documented. We
      review the current literature on the use of pulmonary metastasectomy in patients
      with soft-tissue sarcoma, as well as survival data after such treatment.
      Osteogenic sarcoma is not included in this discussion.

PMID- 10887635
TI  - Clinical trials referral resource. Current clinical trials in endometrial cancer.

PMID- 10887636
TI  - AIDS-related Kaposi's sarcoma: current treatment options, future trends.
AB  - Kaposi's sarcoma (KS) is the most common malignancy associated with the acquired
      immunodeficiency syndrome (AIDS). Recent years have witnessed a decline in the
      overall incidence of AIDS-related KS, as well as a greater understanding of the
      pathogenesis of this disease. Despite these occurrences, AIDS-related KS remains
      an incurable disease that can create many psychosocial problems for patients and
      can adversely affect their quality of life. Clinical management of AIDS-related
      KS has proven to be challenging. Traditional treatment approaches for both local
      and visceral lesions have been palliative in intent. Clinical studies have shown
      alitretinoin gel (Panretin) to be a useful alternative or adjunct to other
      treatments for the management of cutaneous KS lesions. Other therapies, such as
      antiangiogenesis compounds and cytokine inhibitors, are under investigation in
      clinical trials, and pathogenesis-directed therapies, such as anti-human
      herpesvirus type 8 agents, show promise for the effective control of this
      disease. This review highlights the epidemiology and pathogenesis of AIDS-related
      KS, and describes various local and systemic therapies, with a focus on new and
      emerging treatments.

PMID- 10887637
TI  - Update on low malignant potential ovarian tumors.
AB  - Low malignant potential (LMP) ovarian tumors represent a small subset of
      epithelial ovarian cancers that were first identified 70 years ago but were
      recognized in a systematic way only within the last 30 years. These lesions
      afflict women at a much younger age than invasive ovarian cancer, behave in a
      more indolent manner, and have a much more favorable prognosis. The management of
      women with LMP tumors is primarily surgical; adjuvant therapy plays little role
      in early disease and its use in advanced disease is not well defined. Ongoing
      investigations are attempting to define prognostic factors that may assist
      clinicians in the appropriate application of postoperative therapy.

PMID- 10887638
TI  - Current status of voice restoration following total laryngectomy.
AB  - Total laryngectomy is the surgical procedure traditionally used to treat patients
      with advanced-stage cancer of the larynx. The impairments resulting from removal
      of such a small organ are, indeed, profound. They include loss of voice and
      speech; altered respiration, necessitating a permanent breathing opening in the
      neck; and diminished sense of smell and taste. When one considers these factors,
      successful treatment of laryngeal cancer cannot be measured by survival rate
      alone. Rapid, effective restoration of voice and speech is one of the primary
      focuses of rehabilitation and is pivotal to the prevention of the potential
      psychosocial and economic consequences of total laryngectomy. This article
      focuses on the methods of voice restoration currently being employed to
      reestablish the ability to speak.

PMID- 10887639
TI  - Purine nucleoside analogs in indolent non-Hodgkin's lymphoma.
AB  - This article details both the contribution of the purine nucleoside analogs to
      the current management of relapsed indolent non-Hodgkin's lymphoma (NHL) and the
      role of pentostatin (Nipent) in that management. Of the three purine nucleoside
      analogs, pentostatin has received the least attention with regard to the
      management of indolent NHL. Although data in the literature appear to indicate
      that fludarabine (Fludara) and 2-chlorodeoxyadenosine (cladribine [Leustatin])
      are more active in NHL, this conclusion could be flawed because many of the
      studies investigating pentostatin in indolent NHL have contained a large number
      of patients previously treated with the other purine analogs. As these agents are
      most likely cross-resistant, it is unfair to conclude that pentostatin is less
      active. Recently, there has been interest in using a new, more protracted
      schedule of 2 mg/m2/d of pentostatin for 5 days. Although the schedule used in
      the trials conducted in indolent NHL might not be optimal, pentostatin has
      nevertheless shown significant activity in these disorders.

PMID- 10887640
TI  - CD26 in T-cell lymphomas: a potential clinical role?
AB  - T-cell non-Hodgkin's lymphomas are a heterogeneous group of diseases that differ
      markedly in terms of their clinical behavior and prognosis. In recently developed
      classification systems, the sites of initial disease presentation assume a more
      prominent role in subgroup delineation. CD26, a structure with an integral role
      in human T-cell function that serves as the binding protein to adenosine
      deaminase, has been identified recently as a potential marker for certain
      aggressive T-cell lymphomas. To translate our knowledge of the basic biology of
      CD26/adenosine deaminase into clinical practice and to develop specific treatment
      for T-cell lymphomas based on CD26 expression, we, at M. D. Anderson Cancer
      Center, have initiated a phase II trial. This trial will evaluate the effect of
      pentostatin (Nipent), a potent adenosine deaminase inhibitor with known efficacy
      against T-cell malignancies, on relapsed/refractory T-cell lymphomas in relation
      to CD26 expression.

PMID- 10887641
TI  - Pentostatin and rituximab in the treatment of patients with B-cell malignancies.
AB  - Both pentostatin (Nipent) and rituximab (Rituxan) have single-agent activity in B
      cell malignancies, including indolent and intermediate-grade non-Hodgkin's
      lymphoma (NHL). Pentostatin is also active in pretreated patients with chronic
      lymphocytic leukemia (CLL). In spite of current treatment modalities, few
      patients with these diseases are cured. The combination of rituximab and
      pentostatin is an attractive treatment option because both drugs have a limited
      toxicity profile and can be delivered on an outpatient basis. We describe the
      design of a phase II multicenter study to evaluate the safety and efficacy of
      pentostatin in combination with rituximab in patients with previously treated and
      untreated low-grade NHL and CLL.

PMID- 10887642
TI  - Combination therapy with purine nucleoside analogs.
AB  - Pentostatin (Nipent) has demonstrated significant activity as a single agent in
      patients with low-grade B- and T-cell lymphomas, but thus far, clinical
      experience with combinations of pentostatin and other agents is limited. A study
      of alternating administration of pentostatin and high-dose interferon-alfa-2a
      (Roferon A) in cutaneous T-cell lymphoma patients has been undertaken and has
      demonstrated a 41% response rate, with tolerable toxicity. Studies combining
      pentostatin with alkylating agents, including chlorambucil (Leukeran) and
      cyclophosphamide (Cytoxan, Neosar) in patients with chronic lymphocytic leukemia
      (CLL) have reported significant immunosuppression and have required dose
      modifications of one or both agents. Recently, a clinical trial was initiated to
      evaluate the combination of pentostatin and cordycepin, a novel purine analog, in
      patients with terminal deoxynucleotidyl transferase-positive acute lymphocytic
      leukemia, based on in vitro data demonstrating the significant synergy of this
      combination.

PMID- 10887643
TI  - Pentostatin treatment of cutaneous T-cell lymphoma.
AB  - Mycosis fungoides is an indolent primary cutaneous T-cell lymphoma (CTCL) that
      usually progresses from localized skin lesions to systemic disease. Sezary
      syndrome is a distinct variant characterized by generalized erythroderma and
      circulating cerebriform cells in the peripheral blood. The malignant cell in both
      diseases is a mature T cell, usually with a CD4-positive, CD8-negative phenotype.
      Among the treatment modalities used in these diseases are skin-directed therapy,
      single-agent and combination systemic chemotherapy, and, more recently,
      bioimmunotherapy. Pentostatin (Nipent), a potent inhibitor of adenosine
      deaminase, has activity in a wide range of lymphoid malignancies. At The Royal
      Marsden Hospital, we treated 29 cutaneous T-cell lymphoma patients with
      pentostatin, including 16 with Sezary syndrome, 5 with mycosis fungoides, and 8
      with other cutaneous T-cell lymphomas. The median age of patients was 61 years
      (range, 26 to 87 years), with a male-female ratio of 2.5:1. The majority (N = 20)
      had received prior therapy. Pentostatin was administered at a dose of 4 mg/m2/wk
      for 4 weeks, and injections were continued every 1 to 2 weeks until maximum
      response. The overall response rate was 35%. However, only patients with Sezary
      syndrome achieved a good response, demonstrating an overall response rate of 62%
      (three complete responses plus seven partial responses). The median disease-free
      interval for responders was 9 months (range, 3 to 84 months). There was no
      significant treatment-related toxicity. We conclude that pentostatin is an
      effective single-agent therapy for patients with Sezary syndrome but not for
      those with other cutaneous T-cell lymphomas.

PMID- 10887645
TI  - Magnetic resonance imaging for intra-abdominal malignancy.

PMID- 10887644
TI  - Infectious complications of pentostatin therapy.
AB  - Managing the infectious complications associated with pentostatin (Nipent), used
      alone or in combination with other agents in patients with low-grade lymphomas,
      poses a significant problem for clinicians. Since there is limited experience
      with these therapies, definitive treatment recommendations concerning prophylaxis
      cannot be made. The panel members discussed the use of valacyclovir (Valtrex) to
      provide prophylaxis for herpes zoster, trimethoprim/sulfamethoxazole for
      Pneumocystis, and acyclovir (Zovirax) for varicella zoster. They also considered
      combinations of pentostatin with agents such as interferon, rituximab (Rituxan),
      and chlorambucil (Leukeran) and their effect on the immune system. The biology of
      B and T cells was discussed, with an emphasis on clinical application.

PMID- 10887646
TI  - Magnetic resonance imaging of the abdomen: applications in the oncology patient.
AB  - Cross-sectional imaging of the abdomen in oncology patients presents unique
      challenges and opportunities. A close working relationship between the oncologist
      and radiologist is essential for the exchange of the clinical and imaging
      information necessary for optimizing patient diagnosis and management. Compared
      to helical computed tomography (CT), magnetic resonance imaging (MRI) of the
      abdomen and pelvis offers important advantages, including superior soft-tissue
      contrast. The multiplanar capabilities of MRI allow for direct coronal or
      sagittal imaging, providing a truer anatomic presentation of abdominal and pelvic
      masses. Recent advances in MRI, including the use of intravenous (i.v.) and oral
      contrast agents, the development of high-performance imagers, and improved
      surface coil designs, facilitate more rapid abdominal imaging with superior image
      quality. All of these features combine to produce a versatile imaging examination
      with exquisite sensitivity for depicting abdominal and pelvic tumors. In this
      article, we will review the clinical applications for hepatic and extrahepatic
      abdominal MRI in the oncology patient. The MRI techniques and protocols described
      can be applied to most commercially available high-field magnetic resonance
      imagers.

PMID- 10887647
TI  - Diagnostic evaluation of hepatocellular carcinoma in a cirrhotic liver.
AB  - Hepatocellular carcinoma (HCC) is one of the world's most common cancers. It is
      closely associated with cirrhosis, especially that due to viral hepatitis. The
      incidences of viral hepatitis and HCC are rising steadily in the United States.
      When symptomatic, HCC is usually unresectable and associated with a median
      survival of less than 6 months. Nodular lesions of undetermined malignant
      potential are often found in cirrhotic, explanted livers. There appears to be a
      continuum of increasing malignant potential from regenerating nodules to
      dysplastic nodules and to HCC. Pathologic differentiation of high-grade
      dysplastic nodules from HCC is often difficult. Early diagnosis offers the best
      potential for curative intervention. Screening of high-risk patient populations
      using serum alpha-fetoprotein and ultrasound has been attempted but is hindered
      by low sensitivity and specificity. The multinodularity and vascular flow
      anomalies of the cirrhotic liver complicate imaging. However, recent advances in
      magnetic resonance imaging technology allow for more accurate examination of the
      liver. We review the current status of hepatic imaging techniques and the results
      of screening a high-risk population for HCC.

PMID- 10887648
TI  - Comparison studies of CT and MRI in patients with hepatic metastases.
AB  - The increasing use of systemic and directed liver therapy for patients with
      hepatic metastases has created a demand for improved accuracy of noninvasive
      imaging techniques. Computed tomography (CT) and magnetic resonance imaging (MRI)
      are the most common studies used for imaging the liver in oncology patients. Both
      modalities have undergone substantial technical improvement in the past decade,
      and it is often unclear which technique is better suited to specific clinical
      circumstances. This article will review the major recent developments in each
      modality, including dual-phase spiral CT, CT angiography, ultrafast MRI, and MRI
      enhanced with liver-specific contrast agents. Studies that directly compared
      state-of-the-art CT and MRI will be emphasized. This review will give the reader
      a better understanding of the capabilities and limitations of these techniques
      and will clarify which is best used for specific clinical situations.

PMID- 10887649
TI  - Hepatic imaging with iron oxide magnetic resonance imaging.
AB  - The management of hepatic tumors presents a challenging problem. The natural
      history of primary and metastatic liver lesions portends a poor prognosis.
      However, surgical resection and newer ablative techniques have had a great impact
      on cure rates. Unfortunately, the majority of newly diagnosed patients have
      surgically unresectable disease. Advances in hepatic imaging have improved the
      preoperative evaluation of malignant lesions and greatly assisted in selecting
      patients for surgical resection or other interventions. Currently, a number of
      modalities are available for the evaluation of hepatic tumors. This article
      provides an overview of some of the modalities currently in use, examines the
      role of iron oxide magnetic resonance imaging (MRI), and relates experience with
      its use at Baylor University Medical Center.

PMID- 10887650
TI  - Eovist Injection and Resovist Injection: two new liver-specific contrast agents
      for MRI.
AB  - Eovist Injection (gadolinium-EOB-DTPA) is selectively taken up by hepatocytes,
      which will increase the signal intensity of normal liver parenchyma on T1
      weighted images. This results in improved lesion-to-liver contrast because
      malignant tumors either do not contain hepatocytes or their functioning is
      hampered. Following intravenous (i.v.) bolus injection, Eovist Injection is
      excreted by both the renal and biliary routes. Clinical trials have evaluated the
      safety and efficacy of Eovist Injection up to a dose of 100 mumol/kg body weight.
      Resovist Injection (SHU-555A) contains iron-oxide nanoparticles coated with
      carboxydextran and is administered as an intravenous bolus injection at a fixed
      volume dose, dependent on body weight. The uptake of Resovist Injection in the
      reticuloendothelial (RES) cells results in a decrease of the signal intensity of
      normal liver parenchyma on both T2- and T1-weighted images. Due to the altered
      phagocytic distribution and activity, the signal intensity in most metastatic
      tumors is not affected, resulting in improved lesion-to-liver contrast. Both
      Resovist Injection and Eovist Injection have exhibited acceptable safety profiles
      in clinical trials, and have the potential to provide additional information
      regarding lesion detection, classification, and characterization.

PMID- 10887651
TI  - Environmental factors and the distribution of mansonelliases in southern
      Venezuela.
AB  - The distribution of mansonelliases and their relation to various quantitative
      criteria were determined through the study of 1,057 subjects in 17 localities in
      ten regions of Amazonas State and Bolivar State. The total prevalence among the
      blood samples, determined through the Knott technique, was 18.54%. 11.26% were
      parasited by Mansonella perstans, 9.93% by Mansonella ozzardi, and 2.63% by both
      species. The average of microfilaremia was 48.19 mf/mL of blood in M. perstans
      and 13.79 mf/mL in M. ozzardi. In the regions studied, M. ozzardi has a wider
      area of distribution than M. perstans. Prevalence, average number of parasites
      per host, and the infection index have a positive and statistically significant
      correlation with the total annual precipitation mean for each region for M.
      perstans; in the case of M. ozzardi the quantitative parameters are positively
      correlated with the altitude of each region, this correlation being statistically
      significant. With respect to type of vegetation, M. perstans had a higher
      infection index in Amazonian caatinga transition in pluvial lowland forest, and
      M. ozzardi in semideciduous forest of the alisio type. Therefore two types of
      transmission, M. ozzardi-Simulium and M. perstans-Culicoides are suggested.

PMID- 10887652
TI  - Inventory of wild rodents and lagomorphs as natural hosts of Fasciola hepatica on
      a farm located in a humid area in Loire Atlantique (France).
AB  - With the objective of studying the role of wild fauna in the epidemiology of
      fasciolosis disease, a definitive wild-host inventory was carried out in a french
      farm where infected domestic hosts (cows) cohabit with wild potential ones. Liver
      flukes, faecal eggs and antibodies were looked for in lagomorphs (Oryctolagus
      cuniculus) and rodents (Myocastor coypus, Ondatra zybethicus, Rattus norvegicus,
      Arvicola sapidus and micromammal species) trapped in the study area. Presence of
      Fasciola hepatica was detected in two species: O. cuniculus and M. coypus.
      Infection rates were respectively 34% (42/124) and 55% (106/193). Liver flukes
      were found in 78 M. coypus (n = 192) and 11 O. cuniculus (n = 35). No other
      species was infected by F. hepatica. The number of animals shedding fluke eggs
      was higher in M. coypus (49 out of 127 sampled; 38.6%) than in O. cuniculus (two
      out of 17 sampled; 11.7%). The results indicate that M. coypus may play a role in
      the maintenance and the dissemination of F. hepatica in various environments and
      open a discussion on the role of other natural wild hosts.

PMID- 10887653
TI  - Diagnosis of canine echinococcosis: comparison of coproantigen detection with
      necropsy in stray dogs and red foxes from northern Jordan.
AB  - The sandwich enzyme linked immunosorbent assay (ELISA) was used as a diagnostic
      test for Echinococcus granulosus infection by detecting coproantigens in 94 stray
      dogs Canis familiaris and eight red foxes (Vulpes vulpes) from northern Jordan.
      The results were analyzed in relation to actual helminth infection as revealed by
      necropsy. The infection rate of dogs with E. granulosus was 13.8% with a worm
      load ranging between 3-> 10,000 per infected dog. In contrast, eight of 13 E.
      granulosus infected dogs were coproantigen positive (overall sensitivity 61.5%).
      The sensitivity increased to 87.5% and 100% in dogs harboring > 20 and > 100
      worms/dog, respectively. The specificity of coproantigen-ELISA was 91%. The
      greatest cross-reactivity was found in dogs infected with Dipylidium caninum. The
      positive and negative predictive values for the coproantigen-ELISA test were 50%
      and 94.2%, respectively. Thus, a coproantigen negative dog is most probably truly
      negative for E. granulosus. In contrast, a coproantigen positive dog may not be
      truly positive for E. granulosus, except if it has a high worm burden of > 100
      worms/animal.

PMID- 10887654
TI  - Role of streptococcal infection in the acute pathology of lymphatic filariasis.
AB  - Growing evidence suggest that secondary bacterial, mainly streptococcal,
      infections contribute significantly to recurrent episodes of acute
      adenolymphangitis (ADL) of filarial origin. We examined the role of group A
      streptococci in the progression of lymphedema in Polynesian patients with
      filariasis-related ADL (22 cases) or chronic pathology (10 cases), or with
      erysipela (10 patients) and, as controls, in 20 healthy adults. Antistreptolysin
      O (ASLO) and anti-streptodornase B (ASDB) titers were systematically determined
      in parallel to parasitological and biochemical tests. ASLO and ASDB assays were
      positive in 100% of erysipela, 75% of filarial ADL as compared to 50% of chronic
      pathology and 39% of healthy controls. Interestingly, by opposition to ASLO
      titers which were not significantly different between the four groups, ASDB
      titers were higher in ADL (p = 0.019) and erysipela (p = 0.002) than in controls.
      These results support the hypothesis that recurrent streptococcal infections may
      have an important role in the pathogenesis of ADL in lymphatic filariasis.

PMID- 10887655
TI  - Involvement of the mitogen-activated protein (MAP) kinase signalling pathway in
      host cell invasion by Toxoplasma gondii.
AB  - Little is known about signalling in Toxoplasma gondii, but it is likely that
      protein kinases might play a key role in the parasite proliferation,
      differentiation and probably invasion. We previously characterized Mitogen
      Activated Protein (MAP) kinases in T. gondii lysates. In this study, cultured
      cells were tested for their susceptibility to Toxoplasma gondii infection after
      tachyzoite pretreatment with drugs interfering with MAP kinase activation
      pathways. Protein kinases inhibitors, i.e. genistein, RO31-8220 and PD098059,
      reduced tachyzoite infectivity by 38 +/- 4.5%, 85.5 +/- 9% and 56 +/- 10%,
      respectively. Conversely, protein kinases activators, i.e. bombesin and PMA,
      markedly increased infectivity (by 202 +/- 37% and 258 +/- 14%, respectively).
      These results suggest that signalling pathways involving PKC and MAP kinases play
      a role in host cell invasion by Toxoplasma.

PMID- 10887656
TI  - In vivo antileishmanial action of Ir-(COD)-pentamidine tetraphenylborate on
      Leishmania donovani and Leishmania major mouse models.
AB  - Ir-(COD)-pentamidine tetraphenylborate which has previously been studied on
      promastigote forms of Leishmania, was investigated for its antileishmanial
      properties compared with pentamidine used as reference compound. In vitro, the
      iridium complex had the same IC50 value on intracellular forms of Leishmania as
      pentamidine (15 microM). In vivo, the compound could not be injected
      intravenously due to the DMSO excipient so that the treatments were performed
      intraperitoneally or subcutaneously. On the L. donovani LV9/Balb/C mouse model,
      the iridium complex was not toxic after intraperitoneal treatment at 232
      mg/kg/day x 5 or 147 mumoles/kg/day x 5, whereas all the mice died within five
      days when treated at the same dose with pentamidine isethionate. However, only
      23% of parasite suppression was observed with the iridium complex. On a L. major
      MON 74/Balb/C mouse model, susceptible to intravenously administered pentamidine
      at 6.7 mumoles/kg/day x 5 (54% of parasite suppression), the iridium complex
      exhibited 32% of parasite suppression after a treatment at 76 mumoles/kg/day x 5
      administered subcutaneously. This slight activity is of interest since
      pentamidine isethionate is not active under these conditions. Transmission
      electron microscopy of amastigotes from infected and treated mice show
      aggregation of ribosomal material, distension of the nuclear membrane and kDNA
      depolymerization. The mechanism of action therefore involves several targets:
      membranes, ribosomes and kDNA. According to our results, the Iridium complex is a
      suitable candidate to be encapsulated in drug carriers such as liposomes or
      nanoparticles.

PMID- 10887657
TI  - Histological and histoquantitative study of the rat parotid gland after
      Trypanosoma cruzi infection.
AB  - The present study deals with the morphology of the rat parotid gland and its
      changes after Trypanosoma cruzi infection. The glands of control and infected
      animals were analyzed by histologic and histoquantitative methods. After 18 days
      of infection with T. cruzi, a significant reduction of the density of the volume
      of the acini and duct system, as well as a significant increase in the amount of
      connective tissue was noted. In addition, these animals displayed an increase in
      the number of cells undergoing mitosis. In the 45 day infected rats, there was
      return to the normal pattern. It is suggested that in the infected animals the
      decrease in body weight could be responsible for retarded sexual maturity,
      leading to the lower level of testosterone. It can be assumed that decreased
      levels of epidermal growth factor (EGF) and neural growth factor (NGF) caused by
      the lack of testosterone in infected animals also contribute to the atrophy of
      the parotid gland and to the proliferation of the connective tissue.

PMID- 10887658
TI  - Zoosporulation of a new Perkinsus species isolated from the gills of the
      softshell clam Mya arenaria.
AB  - A gill-associated Perkinsus sp. isolated from the softshell clam (Mya arenaria)
      is described as a new species, P. chesapeaki sp. nov. Examination of the parasite
      in seawater cultures revealed life cycle stages and zoosporulation processes
      similar to those described for other species of the genus Perkinsus.
      Prezoosporangia developed thickened cell walls upon contraction of the cytoplasm
      and development of a distinctive clear area between the cell wall and the
      protoplast. Successive bipartition of the protoplast led to the formation of
      hundred's of zoospores within mature sporangia. Zoospores were released into
      seawater through one or more discharge tubes. Ultrastructural studies revealed an
      oblong zoospore possessing two flagella that arose from a concave side located in
      the upper third of the zoospore body. The anterior flagellum possessed a
      unilateral array of hair-like structures. A large anterior vacuole and
      basolateral nucleus dominated the cytoplasm of the zoospore body. The presence of
      a rudimentary apical complex including an open-sided conoid, rhoptries,
      micronemes, and subpellicular microtubules were also discerned. Differences in
      zoospore morphology, and sequence analyses of two genes previously reported,
      support the designation of the gill-associated Perkinsus from the softshell clam
      as a new species.

PMID- 10887659
TI  - On Eimeria bragancaensis n. sp. (Apicomplexa: Eimeriidae) and tissue-cysts of an
      unidentified protozoan in the bat Peropteryx macrotis (Chiroptera:
      Emballonuridae) from Amazonian Brazil.
AB  - A description is given of the mature oocysts and endogenous stages of Eimeria
      bragancaensis n. sp., from the small intestine of the bat Peropteryx macrotis
      from north Brazil. Oocysts are spherical to subspherical, 15.9 x 14.6 microns
      (range 14-17 x 14-17.7). The wall is of two layers: an outer, thicker one which
      is of a brownish-yellow colour and striated (pitted), and an inner one which is
      thin and colourless. The outer layer is frequently lost. No micropyle or oocyst
      residuum present, but the oocyst usually contains one or two polar bodies.
      Sporocysts 8.4 x 5.3 microns (range 6.25-9 x 4-6) with inconspicuous Stieda and
      substiedal bodies. Endogenous stages are intracytoplasmic in the epithelial cells
      of the small intestine, above the host-cell nucleus. Stages of merogony and
      gametogony are described. Abundant tissue-cysts of an unidentified protozoan,
      containing from 1-4 zoites, were found in the parenchyma cells of the liver and,
      less frequently, in the lamina propria of the small intestine. Their possible
      nature is discussed.

PMID- 10887660
TI  - [Schilbetrematoides manizani n. sp. (Dactylogyridea) monogenean parasite of
      Schilbe mandibularis (Gunther, 1867) (Schilbeidae) in the Ivory Coast].
AB  - The authors describe a new species in the genus Schilbetrematoides Kritsky &
      Kulo, 1992 from the gills of Schilbe mandibularis (Gunther, 1867) (Schilbeidae)
      caught in the rivers Bia and Agneby in Ivory Coast. S. manizani n. sp. differs
      from S. pseudodactylogyrus Kritsky & Kulo, 1992, a parasite of Schilbe
      intermedius Ruppell, 1832 by having morphologically distinct gripi.

PMID- 10887661
TI  - [Phlebotomine sandflies (Diptera-Psychodidae) of the isle of Cyprus. I-
      Description of Phlebotomus (Transphlebotomus economidesi n. sp].
AB  - Description of a new palearctic species from Cyprus: Phlebotomus
      (Transphlebotomus) economidesi. The deposited holotype is a female because of the
      particularity of the streaked spermathecae and its non dilated ducts. Four to six
      spines are implanted on the style of the male, but its differential diagnosis
      with the closely related species P. mascittii and P. canaaniticus is difficult.
      The distributions of these Transphlebotomus species are mentioned.

PMID- 10887663
TI  - From holy war to opium war? A case study of the opium economy in north-eastern
      Afghanistan.
AB  - This paper examines the recent growth of the opium economy in north-eastern
      Afghanistan. A detailed analysis of one village in Badakshan Province reveals
      profound changes in the local economy and social institutions. The paper
      describes two major shifts in the local economy: first, the switch from wheat to
      poppy cultivation; and second, the shift from the livestock trade to the opium
      trade. It then examines the underlying causes and impacts of the opium economy on
      social relations in the village. Although a case study of a community living on
      the margins of the global economy, it is argued that these changes have important
      implications for international policymakers. The emergence of the opium economy
      in north-eastern Afghanistan is symptomatic of new and expanding forms of trans
      border trade associated with the restructuring of the global political economy.

PMID- 10887662
TI  - [Phlebotomine sandflies (Diptera-Psychodidae) of the isle of Cyprus. II-
      Isolation and typing of Leishmania (Leishmania infantum Nicolle, 1908 (zymodeme
      MON 1) from Phlebotomus (Larroussius) tobbi Adler and Theodor, 1930].
AB  - During two surveys conducted in Cyprus (August 1998 and September 1999), 2,910
      phlebotomine sandflies females were caught by CDC miniature light traps then
      dissected under binocular and examined on microscope. Eleven species were
      identified: Phlebotomus papatasi, P. sergenti, P. jacusieli, P. alexandri, P.
      tobbi, P. galilaeus, P. mascittii, P. economidesi, Sergentomyia fallax, S. minuta
      et S. azizi. The Larroussius species (P. galilaeus and P. tobbi) are the most
      abundant (more than 60% of our captures). Promastigotes were isolated from one
      specimen identified as P. tobbi. A Leishmania stock was successfully cultured and
      identified by isoenzyme characterisation as belonging to L. infantum zymodeme MON
      1. The same zymodeme was isolated and identified from four dogs too. Because of
      the absence of usual vectors of L. infantum in the eastern part of the
      Mediterranean basin (P. neglectus and P. syriacus), and according to its
      distribution in Cyprus, P. tobbi constitute certainly a good local vector. It
      seems to be not very anthropophilic, that could explain the very few human cases.

PMID- 10887664
TI  - Uncovering local perspectives on humanitarian assistance and its outcomes.
AB  - This paper draws on a study of Angolan refugees in Zambia to suggest ways that
      the perspectives and interests of the local population can be included in the
      assessment of relief interventions. Taking an actor-oriented approach, the paper
      suggests stepping back from the categorisation of the situation as an emergency
      and particular groups of people as the beneficiaries. Such categories are imposed
      from outside and may not reflect local people's outlook on the situation. In the
      case of Angolans in Zambia, the category of refugees had dissolved in the border
      villages to the extent that it was practically impossible to distinguish between
      refugees and hosts. This was in contrast to the official settlements where people
      were marked out as refugees and the label was maintained and reproduced over many
      years. Investigating outcomes in the border villagers in terms of refugees and
      the refugee problem would have been futile. The paper calls for evaluations of
      humanitarian assistance in complex emergencies to look beyond the 'beneficiaries'
      and to investigate the wider context of 'normality'. Neglecting the life and
      world of local people will make it impossible to understand the process by which
      external interventions are mediated at the local level to give particular
      outcomes, and valuable lessons which could help alleviate suffering will be lost.

PMID- 10887665
TI  - Coping strategies developed as a result of social structure and conflict: Kosovo
      in the 1990s.
AB  - The end of 1989 brought with it political and economic decisions which resulted
      in Kosovo being stripped of its autonomy and the Albanian population being
      expelled from their jobs. These facts combined with ethnic tensions created a
      decade of conflict and oppression affecting hundreds of thousands of innocent
      civilians. Thousands of Kosovars moved overseas to seek work to support families
      at home, altering the way of life of the population of Kosovo irredeemably. The
      loss of income had serious repercussions on food security throughout the 1990s;
      possibilities of purchasing food were diminished, control on goods in 1998
      reduced availability of foodstuffs, conflict affected accessibility to markets
      and shops and consequently food intake and nutritional status was compromised.
      The most vulnerable were those who had no family members overseas. Mass
      displacement of population due to ethnic cleansing during the war of spring 1999,
      further jeopardised food security status. Destruction at this time rendered large
      parts of Kosovo useless and resulted in a shift in the determinant of
      vulnerability in the post-war period: destruction of houses, land, livestock and
      agricultural products as well as loss of family members, became a far more
      pertinent indicator of food insecurity. The strong and clear links between
      conflict, socio-economic issues and food security are highlighted and discussed
      in this paper.

PMID- 10887666
TI  - Making exchange entitlements operational: the food economy approach to famine
      prediction and the RiskMap computer program.
AB  - The effect of production failure or some other shock on household income and food
      supply depends upon: (a) the pattern of household income, and (b) its ability to
      compensate for any deficit which may have occurred, for example, by the sale of
      assets or finding additional paid employment. The corollary is that the
      prediction of the likely effect of some event on the future state of the economy
      or food supply of a population of households requires an understanding of the
      economy of the households concerned and the economic context to which these
      relate. This paper describes an attempt to develop an approach to prediction
      using a dynamic model of economy based on quantitative descriptions of household
      economy obtained by systematic rapid field-work and summarises the experience of
      the use of this approach to date.

PMID- 10887667
TI  - How is household vulnerability gendered? Female-headed households in the
      collectives of Suleimaniyah, Iraqi Kurdistan.
AB  - This research tries to reach an understanding of the well-being of female-headed
      household members through a comparison to male-headed household members in the
      collectives of the Suleimaniyah governorate in Iraqi Kurdistan. Research was
      undertaken in five collectives in Suleimaniyah during the summer of 1998. The
      research contributes to the current gender and development debates which are
      concerned with improving the understanding of the specific gendered forms of
      disadvantage faced by female-headed households rather than assuming the universal
      poverty of this group. An understanding of well-being is approached through a
      broad conceptualisation of vulnerability in preference to a narrow poverty
      definition. That the findings of this research are complex attests to the multi
      dimensional and mutually constitutive gendered experiences of vulnerability. The
      definitive conclusion to emerge from this research is a refuting of the rhetoric
      fuelled stereotype that households headed by women are at a disadvantage in all
      the dimensions of vulnerability in comparison to households headed by men. The
      research also establishes the methodological necessity of examining intra
      household distributive mechanisms that determine individuals' well-being.

PMID- 10887668
TI  - Use of exfoliative cytology for diagnosis of transmissible venereal tumour and
      controlling the recovery period in the bitch.
AB  - Transmissible venereal tumour (TVT) is a rare vaginal tumour that can be treated
      surgically or cryosurgically as well as by radiotherapy or chemotherapy.
      Vincristine has been found to be very effective for treating TVT. Since vaginal
      secretion or discharge may contain neoplastic cells, the cytological
      identification of TVT cells is possible. The present study was carried out in 12
      bitches. Vaginal smears were obtained with cotton swab from the anterior vagina
      and TVT suspected structures. The smears were stained according to Papanicolaou
      and assessed by light microscopy. Additionally the general condition of the
      patients was evaluated by haematological and radiographic examinations. In
      bitches with TVT vincristine sulphate was administered intravenously at weekly
      intervals. The total treatment period was three to six weeks until no atypical
      cells were found in the smear. This was the case after an average of 3.2 +/- 1.3
      applications. Tumour masses became smaller and by this non-visible from the rima
      vulva after 4.2 +/- 0.7 applications. During the treatment, two of the 12 bitches
      (16.7%) suffered from vomiting and diarrhoea while three (25%) showed
      neutropenia. Twelve months after completion of treatment, the bitches were
      examined again and vaginal smears were taken in order to control the recovery
      process or a possible recurrence of TVT. No atypical cells were found in any
      vaginal smear. By this exfoliative cytology has proved to be a safe and easy
      method for TVT diagnosis and for observing the recovery process.

PMID- 10887669
TI  - [Reactions of dairy cows to ACTH administration and ingestion of liquid feed at
      different age points before and in the course of rearing with automatic milk
      feeding--plasma cortisol, saliva cortisol, hematologic, metabolic variables and
      heart rate].
AB  - On dairy calves (totally 35 animals; 14 male; 21 female) measurements of rectal
      temperature, heart rate and blood values (acid-base balance, Hb, Hk, MCHC, gas
      content and gas pressure, hemoglobin derivatives, cortisol, total protein,
      albumin, blood urea, creatinine, glucose, lactate, Ca, Mg, P, Fe) and of salivary
      cortisol were done before and after i.v. ACTH application and liquid feed intake
      at 5, 15, 40 and 60 days of life age. Mean values of P-cortisol, S-cortisol,
      heart rate and COHb were elevated and those of total protein, albumin, Mg, Hb,
      Hk, O2CAP were decreased after i.v. ACTH and feed intake. Mean glucose and P
      concentration changed differently in younger and older calves after ACTH and
      liquid feed intake. Changes of Ca and Fe concentration were not significant at
      all age points. Effects of gender could be found for cortisol, O2CONT, MCHC,
      total protein, creatinine, lactate, Mg, and Ca at some age points. Initial P
      cortisol levels were higher at 5 and 15 days than at 40 and 60 days of life, the
      levels after stimulation were higher at 5 days than at 15, 40 and 60 days.
      Initial levels of S-cortisol were significantly different between all age points,
      the levels after stimulation were not different. Female calves had significantly
      greater P-cortisol values at 40 and 60 days as male calves and at 40 days greater
      S-cortisol values too. Significant correlations between P-cortisol and S-cortisol
      could be found before stimulation (5 days: r = 0.626; 15 days: r = 0.366; 60
      days: r = 0.357) not thereafter. All measures except P-cortisol, S-cortisol,
      O2SAT, and HHb had significant correlations before and after ACTH and liquid feed
      intake indicating great interindividual variation and individual specificity of
      reaction within this growth period. Results were discussed under the viewpoint of
      reactivity of adrenocortex and steroid distribution concerning organ specific
      effects of steroids in calves.

PMID- 10887670
TI  - [Victor Hofmeister (1829-1994), Konigl. Dresden Veterinary School--contributions
      to digestive physiology and animal nutrition].
AB  - Victor Hofmeister (1829-1894), a chemist, was active between 1862-1894 at the
      Tierarztliche Hochschule Dresden. His common work with Haubner, Siedamgrotzky and
      especially Ellenberger supplied basis information on digestibility of feestuffs
      (sheep, horses) about various clinical-chemical or toxicological questions, but
      particularly about the digestive physiology in horses, pigs, dogs and ruminants.
      The main results of the research group in Dresden outlast the last 100 years and
      represent valuable aspects for present knowledge in this field.

PMID- 10887671
TI  - Virological and serological studies on the role of PI-3 virus, BRSV, BVDV and BHV
      1 on respiratory infections of cattle. I. The detection of etiological agents by
      direct immunofluorescence technique.
AB  - Nasal cells extracted from nasal swabs obtained from 95 cattle with signs of
      respiratory disease, out of eleven different herds, were tested for BHV-1, PI-3
      virus, BRSV and BVDV using direct immunofluorescence technique. Viral antigen
      positive samples were detected in seven out of eleven herds examined. Of the 95
      individual diseased cattle, 19 were found positive for at least one viral
      antigen. It was found that especially BHV-1 and PI-3 virus are important
      causative agents in cattle respiratory disease, both or in combination with other
      pathogenic agents. Multiple infection in virologically positive herds were
      observed in six (9.8%) of 61 animals tested. The findings reveal that single or
      multiple infections of selected viruses may be present in an important range in
      cattle and that direct immunofluorescence technique as a rapid method, based on
      the detection of viral antigen in nasal swab samples, is useful to establish the
      viral aetiology of acute bovine respiratory disease caused by these viruses,
      particularly in the diagnosis of mixed viral infections.

PMID- 10887672
TI  - Electron microscopic studies on conjunctiva associated lymphoid tissue (CALT) in
      Angora goats.
AB  - The purpose of this study was to investigate the electron microscopic structure
      of conjunctiva associated lymphoid tissue (CALT) and to determine the uptake of
      macromolecules from follicle associated epithelium (FAE) of Angora goats. The
      sample tissues taken from lower and upper eyelids of ten 5-6 month-old healthy
      Angora goats were used in this study. The conjunctiva associated lymphoid tissue
      of Angora goats was formed by solitary or aggregate lymphoid follicle and
      follicle associated epithelium which cover these follicle. FAE was formed by
      flattened epithelial cells, lymphocytes, monocytes and polymorph nuclear
      leukocytes but no goblet cells. Ferritin particles were seen on the apical
      surface, in the invaginations, vesicles, vacuoles of flattened epithelial cells.
      It was concluded that these epithelial cells were specialized to uptake
      macromolecules.

PMID- 10887673
TI  - The effects of food withdrawal and darkening on lipid peroxidation of laying hens
      in high ambient temperatures.
AB  - The aim of this study was to investigate the effects of feed withdrawal and
      darkening on the antioxidative status of laying hens in high ambient temperatures
      between 30-40 degrees C. We determined vitamins A and E, lipid peroxidation as
      thiobarbituric-acid reactive substances (TBARS), glutathione peroxidase (GSH-Px)
      and reduced glutathione (GSH) in the serum, liver and muscle. Sixteen week old
      hens (Ross Brown) were divided into 3 groups of 30 hens each. The first group was
      used as a control. Hens in the second (feed withdrawal) group were subjected to
      feed removal between 14-18 h during the summer. Hens in the third (darkening)
      group were subjected to darkening of the hens house with black curtains between
      14-18 h. At the end of 16 weeks, blood serum, liver and breast muscle samples
      were taken from all animals and analysed. Vitamins A and E levels in serum and
      liver were significantly (P < 0.05, P < 0.01) higher in feed withdrawal and
      darkened groups than in control group whereas the serum levels of the darkening
      group were highest. GSH-Px activity and GSH level in liver and muscle were also
      significantly (P < 0.05, P < 0.01) higher in feed withdrawal and the darkening
      group than in control. However, TBARS levels in liver and muscle were
      significantly (P < 0.05, P < 0.01) lower in feed withdrawal and darkening groups
      compared with control group, whereas the level of the darkening group was the
      lowest. In conclusion, we observed that feed withdrawal and darkening of hens in
      high temperatures during summertime resulted in an increase of antioxidant
      enzymes and vitamins levels and in a decrease of lipid peroxidation.

PMID- 10887675
TI  - [Analysis of a suppressor element of mouse Nodal gene in its 5' flanking
      sequences].
AB  - Nodal gene is a member of the TGF-beta superfamily. It is required for the
      formation of the primitive streak during mouse gastrulation. Mice without Nodal
      gene will die due to the lack of mesoderm formation. F9 cells were transiently
      transfected with a series of luciferase reporter constructs containing the
      subcones of Nodal 5' filanking sequences and their deletions. By analyzing the
      luciferase activity of these constructs, a suppressor element was determined at
      about 1 kb up stream the transcription initiation site, around an EcoR I site.
      Its central part was located at about 100 bp downstream of that EcoR I site. It
      could almost totally, suppress the Nodal gene promoter activity, though it had no
      effect on SV40 promoter. It behaved differently in different cell lines. In CHO
      cells, it had an activation activity.

PMID- 10887674
TI  - [Assessment of malaria DNA vaccines in mice and monkeys].
AB  - Cholera toxin B subunit is a good carrier protein and an effective adjuvant which
      can boost both cellular and humoral immunity. DNA fragments encoding B cell, Th
      cell and CTL epitopes of P. falciparum CS, MSA-1, MSA-2 and RESA antigens were
      cloned down-2 stream of cholera toxin B subunit gene in the same reading frame.
      High titer of anti-malaria epitopes antibodies and strong cellular immunogenicity
      were elicited after Balb/c mice were immunized three times with 100 micrograms
      recombinant plasmid DNA dissolved in 100 microliters PBS. A total of 120
      vaccinees were challenged with mouse Plasmodium yoelli to investigate if cross
      protection existed. The protective efficacy was about 60%-80%. Four rhesus
      monkeys were challenged with 10(8) of P. cynomalgi, better results were obtained
      in the groups immunized with mixed plasmids including NANP, AWTE.

PMID- 10887676
TI  - [The expression patterns of genes in different biotypes by genome addition].
AB  - The patterns of SOD, EST and haemoglobin genes expression among the different
      combinations conducted with genome addition were investigated. The erythrocyte
      expression of these isozymes and protein were visualized by histochemical
      staining after polyacrylamide gradient gel electrophoresis. The results of our
      electrophoresis analysis have revealed that biochemical polymorphism exists in
      the combinations, and these genetic variance have resulted from the contribution
      of different genomes. This study provides additional evidence that gene dosages
      can be interpreted from the enzyme patterns and electrophoretic staining
      intensities existed in different ploidies, which suggests that subunit
      interactions for SOD are co-operative and additive. This would indicate that each
      allele could be differentially regulated so that even one-third genome can be
      expressed in triploid individuals. These genetic data could be used to construct
      genome specific varieties, and would not only help to maximize efficiency in the
      use of different biotypes identification, but also help to maximize studying the
      relationship between gene dosage, expression and regulation.

PMID- 10887677
TI  - [The effect of B chromosome on the reproduction of Drosophila albomicans].
AB  - By using three strains with different number of B chromosome (1-2Bs, 0B, > 2Bs)
      on the same genetic background, the effect of B chromosome on the reproduction of
      Drosophila albomicans was studied. Comparison of net reproduction and sex ratio
      among three strains showed that Bs has significantly effect on flies' net
      reproduction. The net reproduction of flies with 1-2Bs, 0B, > 2Bs is 196, 157,
      147, respectively. Significant difference among three strains exists in the early
      stage of reproduction. The sex ratios of three strains are all close to 1:1, no
      significant difference was observed. The results indicated that lower dose of Bs
      enhances the flies' reproduction and fitness, while higher dose of Bs slightly
      reduces flies reproduction and fitness. These results lend the first strong
      support to the heterotic model.

PMID- 10887678
TI  - [The conservative region sequence analysis of PdSox9 in Paramisgurnus dabryanus].
AB  - Degenerate primers within HMG-box analyzed the Sox genes of P. dabryanus. Three
      amplification bands with the length 220, 550 and 1500 bp respectively were
      observed. A novel gene was obtained from the 550 bp band. The identity of
      possible amino acid sequence to Sox9 of human, mouse and chicken is 94%. The
      similarity to HSOX10, MSox10, HSRY, MSry is 87%, 55%, 40% and 47% respectively.
      So, it was named PdSox9. Northern blotting result showed that it overexposes in
      adult testis and brain.

PMID- 10887679
TI  - [Construction of silkworm RAPD molecular linkage map].
AB  - In this research, a RAPD linkage map of Bombyx mori was constructed with
      Dazao/C108 and their F2 generation. The map consists of 182 RAPD loci, of which
      103 loci come from Dazao and from the first 23 linkage groups and the other 79
      loci come from C108 and form the second 16 linkage groups. This map covered a
      total genetic distance of over 1,148.3 cM (centimorgan). It could be integrated
      with the SADF map of the same materials constructed in our laboratory and the
      corresponding RFLP linkage map.

PMID- 10887680
TI  - [Molecular tagging of a new recessive gene for late heading in a rice cultivar
      8987].
AB  - 8987 is a late flowering (lf) indica cultivar. In this study, genetic analysis
      for lf was carried out in the crosses between 8987 and four varieties with
      different heading time. Inheritance of lf in F1 plants and F2 populations clearly
      revealed that the lf of 8987 is controlled by one recessive gene. Bulked
      segregant method and cosegregation analysis in F2 population were used to screen
      molecular markers, which were linked with lf gene. The results showed that the lf
      gene was mapped between the two RFLP marker C213 and RG404 on chromosome 7. The
      tagged gene will be utilized in molecular marker assisted selection in the future
      rice breeding program for new varieties.

PMID- 10887681
TI  - [Screening and study of RAPD markers tightly linked to wheat powdery mildew
      resistance gene Pm2].
AB  - The random amplified polymorphic DNA (RAPD) analysis was made in Pm2 near
      isogenic lines (NILs) with 265 random primers. Seventeen out of the 256 tested
      primers amplified the polymorphic DNA in the NILs. Five of them showed the same
      discriminating results in more than four replications. The polymorphic bands were
      assigned to be OPM08(1600), OPI04(1700), OPH19(1100) and OPE09(900),
      respectively. Using these five polymorphic primers to detect 14 resistant
      materials with Pm2 and 9 susceptible materials without Pm2, only OPI04(1700) was
      amplified in 12 of the 14 resistant materials and absent in all of the 9
      susceptible materials. Further RAPD analysis of (Chancellor x Ulka/8*Cc) F2
      plants by primer OPI04 indicated that the genetic distance of OPI04(1700) to Pm2
      was 12.2 +/- 3.3 cM.

PMID- 10887682
TI  - [Inheritance of resistance to Heterodera glycines race 14 in Huibuzhi black
      bean].
AB  - Heterodera glycines is the most serious disease in the world soybean (Glycine
      max) production. Huibuzhi black bean from Xing County in Shanxi Province, China
      is one of the most important resistant resources. Using a set of host
      differentials for soybean cyst nematode and criterion of race classification as
      well as method of manual inoculation, race 14 was identified as a prevalent one
      in the soil population of the Experiment Station, Institute of Plant Protection,
      Chinese Academy of Agricultural Sciences, Beijing. A sensitive variety #7 Jidou
      as a female donor crossed with Huibuzhi black bean. Their offsprings were
      investigated for resistance to race 14. Two of F1 seedlings demonstrated their
      resistant. Two populations in F2 including 116 seedlings and 78 seedlings in each
      one appeared their own separate ratio that was in common: 43R:21S. A genetic
      hypothesis was proposed that resistance to SCN race 14 in Huibuzhi black bean was
      controlled by three gene pairs arose. Gene reciprocity existed among them: one
      recessive epistasis gene pair and two dominant complementary gene pairs. Random
      30 families in F3 including 10-15 tested seedlings in each family were screened
      for resistance to SCN race 14. The segregate ratio, 19R:38Seg.:7S, among F3
      families confirmed that the presented genetic hypothesis was correct.

PMID- 10887683
TI  - [Studies of molecular marker-assisted-selection for resistance to Fusarium wilt
      in watermelon (Citrullus lanatus) breeding].
AB  - The RAPD marker OPP01/700 proved to be linked to the Fusarium wilt resistant gene
      in watermelon wild germplasm PI296341 was cloned and sequenced, and transferred
      into a SCAR marker. The linked marker was tested to be one copy by Southern
      blotting. The technique of detection of the SCAR-amplified products was
      simplified. These techniques were applied in selecting resistant plants in F3 of
      the introgression of the disease resistant gene. It is the first report in this
      field of transfer ring a RAPD marker linked to disease resistance gene into SCAR
      marker, and establishing the technique of molecular marker-assisted-selection for
      breeding Fusarium wilt resistance cultivars.

PMID- 10887684
TI  - [Cloning and expression of trehalose synthase genes in Escherchia coli].
AB  - Escherichia coli trehalose synthase otsBA genes have been cloned by using
      transposon Mu in vivo. The cloning frequency was 1.45 x 10(-3)/Kanr transductant.
      Genetic complements, endonuclase digestion and partial nucleotide sequencing
      analysis of these clones indicated that otsBA gene was on plasmid Mud5005.
      Subcloning 2.87 kb DNA fragment onto expression plasmids with higher or lower
      copy number and transforming into E. coli recipient strain FF4050, which have
      otsBA genes deleted respectively, the transformed strains obtained ability of
      growth on medium containing 0.5 mol/L NaCl and increased trehalose synthesis
      under high osmotic pressure. Production and accumulation of trehalose may play an
      important role in crop breeding. These studies will lay an important foundation
      for constructing an expression vector with the otsBA genes and transformation to
      tobacco mediated by Agrobacterium, and obtaining ability for drought resistance
      and high osmotic pressure tolerance.

PMID- 10887685
TI  - [Alpha-acetolactate decarboxylase from B. licheniformis AS10106: cloning and
      expression gene in E. coli and S. cerevisiae].
AB  - A genomic library of B. licheniformis AS10106 that contained the alpha
      acetolactate decarboxylase gene(alpha-ALDC) was constructed with vector pUC19 and
      host E. coli JM109 strain. The inserted fragments of foreign DNA ranged from 4 to
      10 kb in the 4800 clones thus obtained. Six positive clones were detected after
      screening the plated library by the method of clony coloration. Subcloning of the
      DNA fragment containing the alpha-acetolactate decarboxylase gene showed that the
      alpha-acetolactate decarboxylase gene was on an 1.6 kb BamH I-EcoR I fragment.
      Preliminary analysis of the enzyme expressed from one recombinant plasmid pGEA
      showed that the properties of the recombinant enzyme, such as the optimal
      temperature and pH of reaction, were identical to those of the native enzyme.
      Using yeast-E. coli shuttle vector pYES2, an expression recombinant plasmid pYEA
      containing B. licheniformis AS10106 alpha-acetolactate decarboxylase gene was
      constructed. S. cerevisiae H158 transformed with pYEA had expressed alpha
      acetolactate decarboxylase activity and shown the ability to reduce the formation
      of diacetyl during beer fermentation.

PMID- 10887687
TI  - [Site-directed mutagenesis of melittin gene and its expression in Escherichia
      coli].
AB  - The cDNA encoding promelittin was obtained from the total RNA of bee poison gland
      by RT-PCR. Moreover, hydroxylamine clearage site was arranged before the melittin
      sequences by site-directed mutagenesis. The expression vector containing the
      mutagenic promelittin sequence with partial sequence of beta-galactosidase was
      constructed. The result of DNA sequence analysis demonstrated that the obtained
      cDNA sequence include the desired codon and the reading frame of fusion gene was
      correct. The induced protein was expressed in Escherichia coli.

PMID- 10887686
TI  - [Studies of gene regulation of de novo biosynthetic pathway of purine in
      Salmonella typhimurium. X. Isolation of purR(am) mutants and preliminary studies
      of amino acid substitution].
AB  - Starting from a super-repressed mutant of purR, 3-18, 439 independent candidates
      of purR- mutants were isolated by using NCE selecting plate with lactose as sole
      carbon source. Among these mutants. 11 amber mutants were detected by introducing
      a tRNA suppressor gene. Cotransduction analysis proved that the amber mutation
      sites of 11 amber mutants all located on purR. Amino acid substitution
      experiments were performed with three tRNA suppressors, supD, supE and supF, for
      each purR(am). The results showed that the same amino acid substitution occurred
      in different site of PurR protein could result in varied effects on purR
      function; different amino acid substitution occurred at the same position of PurR
      protein also could produced varied effects on purR function.

PMID- 10887688
TI  - [Expression and roles of hemoglobin gene in Bacillus subtilis].
AB  - Hemoglobin of the Gram-negative bacterium Vitreoscilla can bind oxygen strongly
      and reduce the oxygen requirement of the bacterium. A recombinant plasmid pAV was
      constructed by inserting the hemoglobin gene (Vgb) to the downstream of the
      promoter of beta-lactase gene of the B. subtilis plasmid pAK4. The plasmid pAV
      was transferred into strain DB104, G331 (a subtilisin-producing B. subtilis) and
      B53 (a xylanase-producing B. subtilis). The subclones and transfer of the Vgb
      gene into pAK4 were detected and confirmed by Dot blotting and electrophoresis
      analysis. The expression of homoglobin was measured by recording CO-difference
      spectra after bubbling CO into the sample cuvette. The production of subtilisin
      and xylanase was increased in the fermentation of the Vgb-expressing strains.
      These results provided a new way to reduce the oxygen requirement and to increase
      the biomass production in the fermentation industry.

PMID- 10887689
TI  - [Studies of the association of pathological myopia in Chinese patients with HLA
      alleles].
AB  - The second exons of the HLA-DQB1 genes in 55 patients with Pathological Myopia
      were amplified and then digested with ApaI, Bsp1286I, BsaHI, BssHII, HaeII,
      HaeIII, HpaII, RsaI to determinate the genotypes and the allele frequencies.
      Among the 16 alleles, HLA-DQB1*0201, *0301, *0303, *0401 alleles in PM patients
      differed significantly from that of the normal ones in the distribution of the
      alleles, and seemed to be the pathogenic genes (P < 0.05; AF = 0.1636, 0.1091,
      0.1636, 0.1091 vs. 0.0400, 0.0300, 0.0400, 0.0200; RR = 4.2886, 3.5350, 4.2890,
      5.0000); While the HLA-DQB1*0601, *0602 frequencies in PM patients were
      remarkably lower than that of the normal ones, which showed the property of
      protective genes (Pc = 0.0000, AF = 0.1182, 0.0818 vs. 0.4300, 0.3100).
      DQB1*05.32, *0504 and *0605 can not be detected. The association of PM with DQB1
      was found for the first time in the world, which has great significance both to
      theoretical study and to clinical diagnosis.

PMID- 10887690
TI  - [The expression of arrhythmic related genes on Xenopus oocytes for evaluation of
      class III antiarrhythmic drugs from ocean active material].
AB  - By techniques of gene clone, microinjection and patch-clamp, human arrhythmic
      related gene Kv1.5 and Kv4.2 are translated mRNA, and injected into Xenopus
      Oocytes, respectively. A pure and single K+ current of ultrarapid delayed
      rectifier K+ current (Ikur) or transient outward K+ current (Ito) is respectively
      expressed on Xenopus Oocytes. This is a modern pharmacological model for
      evaluation class III antiarrhythmic drugs, overcomes many defects such as lacking
      human fresh cardiac muscle cells as material and co-expression of many currents
      on cell membrane. A new compound A1998 from Ocean material is evaluated in this
      model for class III antiarrhythmic functions.

PMID- 10887691
TI  - [Analysis of an inhancer element of mouse Nodal gene in its 5' flanking
      sequence].
AB  - Nodal, a member of TGF-beta superfamily, plays a very important role in the
      mesoderm formation during mouse early development. Mice without the Nodal gene
      will die due to the lack of mesoderm. The flanking sequences of Nodal were
      dissected. By using lucifirase as reporter gene, F9 cells were transfected with a
      series of reporter constructs containing the subclones of the flanking sequences
      and their nested deletions. The effect of these subclones and deletions-2 kb up
      stream the Nodal gene and its cell type specificity was determined.

PMID- 10887692
TI  - [Phylogenetic study of Artemia from China using RAPD and AFLP markers].
AB  - We have applied the techniques of RAPD (random amplified polymorphic DNA) and
      AFLP (amplified fragment length polymorphism) to the analysis of the
      relationships among Artemia species and strains. RAPD markers were successfully
      employed to detect diversity and genetic differentiation among four species of
      brine shrimp: A. franciscana, A. urmiana, A. sinica, and A. parthenogenetica.
      Seventy, ten-base synthetic oligonucleotides were used to amplify a total of 458
      distinct fragments. DNA polymorphisms were found in all the species examined; The
      highest percentage of polymorphic bands found in A. parthenogenetica, was 28.8
      per cent. There are significant differences between bisexual sibling species and
      parthenogenetic populations. A. parthenogenetica provided 94 specific molecular
      markers, while bisexual sibling species gave 27 specific molecular markers. A.
      sinica is a species distinct from the other Old World bisexual species. AFLP were
      used to analyze 15 Artemia species and strains for genetic diversity. They are
      extremely sensitive to even a small sequence variation and more polymorphism than
      RAPD. Using only 10 pairs of primer combinations, we detected 580 AFLP bands of
      which were polymerphic. The RAPD and AFLP techniques are powerful DNA
      fingerprinting methods for classification of Artemia species and strains.

PMID- 10887693
TI  - [Phylogenetic relationships and evolution of yeast-like symbionts of the small
      brown planthoppers based on partial 18S rDNA sequences].
AB  - The yeast-like symbionts are isolated and purified from the small brown
      planthoppers collected from five areas in China. The 18S rDNA sequences of them
      are determined. Combined with the sequences of other fungi, we have constructed a
      comprehensive phylogenetic tree. The results suggested that the taxonomic
      positions of the YLS are in the class Pyrenomycetes in the subphylum Ascomycotina
      and the YLS have the closest relationship with H. chrysospermus. The YLS of
      different areas in China and Japan may belong to different geographical
      populations of one species. We could also draw a conclusion that there are
      independent acquisitions of various symbionts in differentiated hosts.

PMID- 10887694
TI  - [A study of the genetic diversity of common wild rice (O. rufipogon Griff.) and
      cultivated rice (O. sativa L.) by RFLP analysis].
AB  - The genetic diversity of cultivated rice and common wild rice from 10 countries
      in Asia were evaluated by RFLP analysis using 44 probes of single copy. We used
      the parameters such as proportion of polymorphic loci (P), average number of
      alleles per locus (A), average number genotype per locus (Ng), degree of
      heterozygate per locus (Ho) and average gene diversity (Hs) showing genetic
      diversity. It is indicated that the common wild rice from China has the largest
      genetic diversity in the 10 countries, and the secondary is the common wild rice
      from India. The results also showed that the genetic diversity in Chinese common
      wild rice is larger than the genetic diversity in common wild rice of South and
      Southeast Asia. The average gene diversity (Hs) of South Asian wild rice is
      higher than Southeast Asian wild rice, while the parameters value of proportion
      of polymorphic loci (P), average number of alleles per locus (A) and average
      number genotype per locus (Ng), Southeast Asian wild rice is higher than South
      Asian wild rice. It is found that the genetic diversity in cultivated rice is
      obviously lower than in common wild rice. In the detected 44 loci, the number of
      polymorphic loci on O. sativa is as the same as 3/4 in O. rufipogon, the number
      of alleles in O. sativa is as the same as 60% in O. rufipogon, the number of
      genotype in O. sativa is as same as 1/2 in O. rufipogon. In O. sativa, the
      genetic diversity of indica is larger than that of japonica. O. rufipogon from
      China have highest value in degree of hetrozygate per locus (Ho), and Ho of wild
      rice is as two times as cultivated rice. It is showed that in the proceeding of
      wild rice evolved into cultivated rice, Ho and number of alleles was reduced, and
      the genetic diversity was decreased.

PMID- 10887695
TI  - [Genetic studies of blast resistance of indica variety Zhefu 802].
AB  - One indica variety, Zhefu 802, was studied for its inheritance of blast
      resistance by inoculation of two strains Ken54-04 and 95-t2. The B1F1 and F2
      populations from cross of Zhefu 802(R) x Lijiangxintuanheigu (S) and related
      parents were inoculated by spray inoculation method with the two above mentioned
      strains to determine R:S ratio of segregating populations of this cross. The
      results indicated that Zhefu 802 has two dominant resistance genes to strain Ken
      54-04. One of the two genes showed resistant reaction and the other is
      susceptible to strain 95-t2. The allelism test indicated that one gene in Zhefu
      802, which showed resistant reaction to strain 95-t2, is allelic to Pi-i gene
      locus and non-allelic to loci of Pi-a, Pi-sh, Pi-k, Pi-z, Pi-ta, Pi-b, Pi-t. The
      other gene in this variety was also estimated to be different from all of the
      known genes. So it may be an unknown gene. But this point needs to be confirmed
      further.

PMID- 10887696
TI  - [Background analysis of chromosome controling genetic of water use efficiency of
      Triticum].
AB  - Water use efficiency (WUE) of flag leaf of different genetic material was
      measured by LCA-3 model photosynthesis apparatus. The results show as follows:
      The order of flag leaf WUE of different chromosome set is AA > BB > DD > RR.
      Among twenty Chinese Spring ditelosomic, the flag leaf WUE of A ditelosomic set
      is the highest, the high WUE genes locate on 1AL, 2AL, 2AS and 7AS chromosome
      arm. Among seven wheat-S. Cereals addition lines, the high WUE gene locates on 4R
      chromosome, the flag leaf WUE of 5R chromosome is the lowest. In the end of this
      paper, the research advance of stress resistance gene location on the fourth
      chromosome set of Triticum was discussed.

PMID- 10887697
TI  - [An ADAA model and its analysis method for agronomic traits based on the double
      cross mating design].
AB  - According to the double-cross mating design and using principles of Cockerham's
      general genetic model, a genetic model with additive, dominance and epistatic
      effects (ADAA model) was proposed for the analysis of agronomic traits.
      Components of genetic effects were derived for different generations. Monte Carlo
      simulation was conducted for analyzing the ADAA model and its reduced AD model by
      using different generations. It was indicated that genetic variance components
      could be estimated without bias by MINQUE(1) method and genetic effects could be
      predicted effectively by AUP method; at least three generations (including
      parent, F1 of single cross and F1 of double-cross) were necessary for analyzing
      the ADAA model and only two generations (including parent and F1 of double-cross)
      were enough for the reduced AD model. When epistatic effects were taken into
      account, a new approach for predicting the heterosis of agronomic traits of
      double-crosses was given on the basis of unbiased prediction of genotypic merits
      of parents and their crosses. In addition, genotype x environment interaction
      effects and interaction heterosis due to G x E interaction were discussed
      briefly.

PMID- 10887698
TI  - [Studies of the mixoploid variation in banana micropropagated plants].
AB  - A special type of variation--the mixoploid variation, which had a great effect on
      the variation in the production of banana vitroplants, was reported for the first
      time. By means of examining chromosome, isozymes (EST, MDH, POX) and endogenous
      hormones (iPAs, IAA), the varied characters of the mixoploid varianties during
      the propagation in vitro when cultured as explant were investigated. The rate of
      the chromosome aberration in cells was characterized by starting at a much higher
      level and rising more rapidly in the preceding 15 subcultures as compared with
      the control. The rate of the isozyme variation was higher obviously than that of
      the control. The plantlets cloned in vitro from the mixoploid variant were also
      studied. The experiment showed that both the variant rates of chromosome and
      phenotype rose obviously. The mixoploid variant can cause the rate of variation
      to rise during the micropropagation.

PMID- 10887699
TI  - [Expression of Bacillus thuringiensis (Bt) crystal toxin gene in the chloroplast
      of tobacco].
AB  - The 3.5 kb wild-type Bt Cry I A(c) gene and its 3' truncated forms (2.1 kb, 1.8
      kb) were placed under the control of plastid expression signals consisting of the
      strong light-induced psbA promoter and its 3' untranslated region with the aadA
      cassette (Prrn, aadA and psbA3') as a selectable marker. The resulting vectors
      pBT3, pBT8 and pBT22 also contain flanking tobacco plastid DNA homology regions
      to direct insertion of the Bt transgene into the tobacco plastid genome between
      psbA and trnK by homologous recombination. Transformed plastid genomes were
      selectively amplified by growing the cells on spectinomycin medium. Several
      independently transformed lines were obtained at last. The results of Southern
      and Western blot demonstrated that these three kinds of Bt genes had been
      introduced into tobacco plants, and their filial generations are resistant to
      spectinomycin. Insecticidal activity assay with transgenic tobacco leaves
      indicate that some plants have strong toxicity to cotton bollworm. This is the
      first report in China that Bt gene has been introduced and successfully expressed
      in the chloroplast of higher plants.

PMID- 10887700
TI  - [Bacterial genetic diversity in soils and their correlation with vegetation].
AB  - Soil is an important epicenter of biodiversity. Human activity has threatened
      such biodiversity through vegetation shift. As the major type of microbes,
      bacteria have played key roles in material cycling. Since simple morphological
      characters and the failure of the major portion of bacteria in surviving
      artificial cultivation have hindered bacterial diversity from analyses using
      traditional taxonomic approaches, bacterial diversity and its correlation with
      vegetation is less understood. In order to detour cultivation, tag serial
      sequencing strategy was developed in this study, in which a 26 base pair highly
      variable region has been chosen from 16S ribosomal RNA gene as variant
      representing tags, ligated into serials and sequenced. Molecular bacterial
      diversity in soils has been determined using tag types, tag frequencies and
      diversity index as parameters. The correlation of bacterial diversity with
      vegetation has been explored as well. Bacterial diversity and differentiation
      correlate highly with contents of organic matter and nitrogen of soils and
      further vegetation.

PMID- 10887701
TI  - Decisions about extremely low-birth-weight infants.

PMID- 10887702
TI  - Decisions about extremely low-birth-weight infants.

PMID- 10887703
TI  - No justified use of placebos for pain.

PMID- 10887704
TI  - No justified use of placebos for pain.

PMID- 10887705
TI  - No justified use of placebos for pain.

PMID- 10887706
TI  - No justified use of placebos for pain.

PMID- 10887707
TI  - No justified use of placebos for pain.

PMID- 10887708
TI  - No justified use of placebos for pain.

PMID- 10887709
TI  - Nursing knowledge for the 21st century: opportunities and challenges.

PMID- 10887710
TI  - Qualitative outcome analysis: evaluating nursing interventions for complex
      clinical phenomena.
AB  - PURPOSE: To describe a method that allows evaluating nursing interventions
      derived from a qualitative research project, and that shows appropriate
      interventions. ORGANIZING FRAMEWORK: Qualitative research has expanded over the
      last decade and has contributed significantly to understanding patients'
      experiences of health, illness, and injury. Yet the value of qualitative research
      in determining clinical interventions and subsequently evaluating the effects of
      these interventions on patients' outcomes has been limited. This method is used
      to confirm the efficacy of nursing interventions when experience changes over
      time, to extend the repertoire of intervention strategies, and to further
      clinicians' understanding of possible outcomes. DESIGN: From a completed study,
      Qualitative Outcome Analysis (QOA) enhances the identification of meaningful
      intervention strategies and plans for utilization. The researcher identifies the
      type of qualitative data that will enable the interpretation and evaluation of
      interventions, devises a means of data recording and analysis, and finally,
      disseminates the findings. CONCLUSIONS: QOA is a systematic means to confirm the
      applicability of clinical strategies developed from a single qualitative project,
      to extend the repertoire of clinical interventions, and to evaluate clinical
      outcomes.

PMID- 10887711
TI  - A continuity of care integrated literature review, Part 2: Methodological issues.
AB  - PURPOSE: In Part 2 of this two-part series, research designs, methods, and
      measurement of continuity of care are explored. DESIGN: Qualitative, integrated
      literature review of a sample of 38 continuity of care nursing research article
      published 1990-1995. METHODS: Ganong's (1987) stages of the integrative
      literature research review process were followed. A data collection tool was
      designed and pilot tested, and rules for data analysis and interpretation were
      established. Research articles were systematically analyzed and reported using
      descriptive analysis. FINDINGS: Results showed few nursing models, primarily
      convenience sampling and nonexperimental cross-sectional study designs, varied
      data collection methods, and inadequate instrumentation. Measurement criteria
      were diverse and influenced by the perspectives of the measurer. CONCLUSIONS:
      Continuity of patient care was identified as a construct comprised of many
      related and tangential concepts in need of more sophisticated review.
      Recommendations for researchers are discussed.

PMID- 10887712
TI  - Caring for dying patients who have air hunger.
AB  - PURPOSE: To understand nurses' experiences of caring for dying patients who have
      "air hunger." When air hunger occurs in people who are close to death, it often
      triggers increasing panic and breathlessness. Describing this phenomenon is an
      initial step toward a more informed and consistent response to air-hungry
      patients. DESIGN AND METHODS: Phenomenological study of 10 hospice, long-term
      care, oncology, or emergency medicine nurses who cared for air-hungry dying
      patients. Analysis was based on van Manen's guidelines for interpretive
      phenomenology. Interviews with two family members who witnessed their dying
      spouses suffer from air hunger were used to complement the nurses' accounts.
      FINDINGS: Themes of (a) the patient's look-panic beckons, (b) surrendering and
      sharing control, and (c) fine-tuning dying indicated ways nurses responded to
      relieve a patient's air hunger, including being prepared before air hunger
      occurs, calming patients and families, medicating patients, improvising care,
      attending to family members' needs, and drawing a distinction between palliating
      and killing. CONCLUSIONS: The three themes provide a framework for a new vision
      of "doing everything" for a dying person who suffers from air hunger. Care
      encompasses knowing what to do as well as how to stay present during suffering.

PMID- 10887713
TI  - Reducing negative thinking and depressive symptoms in college women.
AB  - PURPOSE: Although cognitive-behavioral interventions have been successful in
      treating depression, no studies were found that focused solely on reducing
      negative thinking via group intervention as a means of preventing depression in
      at-risk groups. The purpose of this randomized controlled trial was to test the
      effectiveness of a cognitive-behavioral group intervention in reducing depressive
      symptoms, decreasing negative thinking, and enhancing self-esteem in young women
      at risk for depression. DESIGN: A randomized controlled trial with 92 college
      women ages 18 to 24 who were at risk for depression was conducted. METHOD:
      Participants were randomly assigned to either the control or experimental group.
      The experimental group participated in a 6-week cognitive-behavioral group
      intervention. Data on self-esteem, depressive symptoms, and negative thinking
      were collected via self-report questionnaires from control and experimental
      groups at baseline, 1 month after the intervention, and at 6-month follow-up.
      Data were analyzed using mixed-model methodology and the Cochran-Mantel-Haenszel
      chi-square test. FINDINGS: Compared to those in the control group, women who
      received the intervention had a greater decrease in depressive symptoms and
      negative thinking and a greater increase in self-esteem, and these beneficial
      effects were maintained over 6-months. CONCLUSIONS: The findings document the
      effectiveness of this cognitive-behavioral group intervention and indicate
      empirical support for the beneficial effects of reducing negative thinking by the
      use of affirmations and thought-stopping techniques on women's mental health.

PMID- 10887714
TI  - A test of Braden's Self-Help Model in adults with chronic pain.
AB  - PURPOSE: To test hypothesized relationships in Braden's Self-Help Model in a
      sample of people with idiopathic chronic pain. Testing theoretical explanations
      and predictions with various clinical populations under different sociocultural,
      economic, climatic, and health system environments provides evidence about the
      applicability of the underlying theory among diverse populations. DESIGN: This
      study was part of a larger randomized, controlled trial of a community-based
      nursing psycho-educational intervention: the Chronic Pain Self-Management Program
      (CPSMP). Pretest and posttest data were collected in 1995-1996 in Newfoundland,
      Canada. METHODS: Participants completed a battery of valid and reliable self
      report instruments to measure pain, disability, uncertainty, resourcefulness,
      self-efficacy, adult role behaviors, and life satisfaction. Two tests of the self
      help model were performed, the first with pretest data (N = 110) and the second
      with 3-month posttest data (N = 102) after half the sample had participated in
      the CPSMP intervention. Causal modeling path analysis was done with the
      Statistical Package for the Social Sciences (SPSS) program and tests of goodness
      of-fit were conducted using EQS for Windows. RESULTS: Results supported the
      overall hypothesized pattern of relationships in the self-help model. Amounts of
      variance explained in the two major outcomes of the model (self-help: 42% to 53%
      and life quality: 45% to 47%) were consistent with results from other studies.
      Indices of goodness of fit showed an adequate fit of the model to the data,
      particularly the posttest data. CONCLUSIONS: Braden's Self-Help Model appears to
      be robust in a variety of clinical populations, among different settings and
      environmental conditions, and provides a useful framework to guide nursing psycho
      educational interventions in chronic illness.

PMID- 10887715
TI  - Opportunities and challenges in clinical nursing research.

PMID- 10887716
TI  - Important attributes of quality health care: consumer perspectives.
AB  - PURPOSE: Despite extensive research on defining and measuring health care
      quality, little attention has been given to consumers' perspectives of high
      quality health care. The purposes of this study were to (a) identify the
      importance to consumers of attributes of health care quality and nursing care
      quality, and (b) examine the relationship of consumer perspectives to health
      status and selected demographic variables. DESIGN: Exploratory. Consumers (N =
      239) were recruited from waiting rooms of clinics and in neighborhoods of a large
      metropolitan area in the Midwestern United States that included both urban and
      suburban populations. METHODS: Participants completed the Quality Health Care
      Questionnaire (QHCQ) and the SF-36 Health Survey. On the QHCQ, they rated the
      importance of 27 attributes of health care and nursing care quality. The SF-36 is
      a 36-item instrument for measuring health status in eight general areas.
      FINDINGS: The most important indicators of high-quality nursing care to consumers
      were: being cared for by nurses who are up-to-date and well informed; being able
      to communicate with the nurse; spending enough time with the nurse and not
      feeling rushed during the visit; having a nurse teach about the illness,
      medications, treatments, and staying healthy; and being able to call a nurse with
      questions. The lowest-rated item was having an opportunity to be cared for by
      nurse practitioners. Ratings differed by race, age, years of education, income,
      and health status. CONCLUSIONS: The importance that consumers place on teaching
      by the nurse was emphasized, particularly among people with less education, low
      income levels, and chronic illnesses.

PMID- 10887718
TI  - Children's rights in clinical research.
AB  - PURPOSE: To address the use of children and children's genetic information in
      research, analyze Icelandic laws as an example, review existing literature on
      children in clinical research, and describe nurses' actions as children's
      advocates. METHOD: An integrated literature review was conducted using
      theoretical and empirical literature on children as human subjects in clinical
      research. Five Icelandic laws were analyzed. FINDINGS: Legal protection of
      children as human subjects is an international issue and is lacking in Icelandic
      legislation. In spite of an identified need to protect children as human
      subjects, research on children's rights in clinical research is scarce. Nurses
      have not taken an active stance in protecting children as human subjects.
      CONCLUSIONS: The recently passed Bill on Health Sector Database in Iceland raises
      questions about protection of human subjects regardless of age and stature. The
      effects of this Icelandic case could have international implications regarding
      centralized health care databases, ownership of data, and related ethical and
      legal decisions.

PMID- 10887717
TI  - Health status of young offenders and their families.
AB  - PURPOSE: To describe the health status of youth committed and detained by the
      Maryland Department of Juvenile Justice. The problem of complex health needs of
      young offenders is gaining importance as the number of youth under the care of
      state juvenile justice systems steadily increases. METHODS: The health status of
      a random sample (N = 350) of male and female committed or detained young
      offenders was assessed utilizing a record review and a self-report health survey.
      RESULTS: Ninety-seven percent of the sample reported levels of physical
      discomfort and 92% reported emotional discomfort. Nearly half (45%) of the youth
      had some medical condition, 53% had been abused, 20% injured, 16% sustained a
      gunshot or stab wound. Of youth reporting physical injury, 12% did not receive
      treatment. Family members, including siblings experienced similar health
      problems. CONCLUSIONS: Patterns of physical and behavioral health problems were
      noted within these families, as were patterns of criminal behavior. Trans
      generational patterns of at-risk behaviors were evident. Most youth (86%)
      perceived themselves to be healthy. However, when specific health indicators were
      examined, discrepancies between health status and health perceptions were noted.

PMID- 10887719
TI  - Use of certificates of confidentiality in nursing research.
AB  - PURPOSE: To discuss the use of Certificates of Confidentiality in nursing
      research. ORGANIZING CONSTRUCT: In situations that are particularly complex,
      sensitive, and in which the participants are extremely vulnerable, a Certificate
      of Confidentiality issued by the U.S. Department of Health and Human Services
      (DHHS) may be useful to help ensure the privacy of research participants.
      SOURCES: Theoretical and research literature, DHHS documents, and research
      experience. FINDINGS AND CONCLUSIONS: Not all research with vulnerable
      populations requires the additional protection provided by Certificates of
      Confidentiality. However, certificates may be indicated in studies in which
      participants and researchers may be exposed to compelled legal disclosure of
      research data.

PMID- 10887720
TI  - Native American graduate nursing students' learning experiences.
AB  - PURPOSE: To identify learning experiences of Native American graduate nursing
      students in a university-based nurse practitioner program. DESIGN: The
      phenomenological approach of Heideggerian hermeneutics. METHOD: A purposive
      sample of 11 Native American graduate students in a nurse practitioner program
      were given the choice of participating in a focus group or completing an
      individual interview to elicit common meanings and shared experiences. FINDINGS:
      Four themes and two constitutive patterns: (a) Native American students'
      worldviews reflected unwritten knowledge that served as a background of common
      understanding, (b) academic environment as a rigid environment with only one way
      to learn and constant evaluation, (c) faculty-student relationship barriers to
      establishing a supportive learning environment, and (d) strategies to survive,
      including a commitment to succeed, conforming to unwritten rules, helping each
      other, and ultimately changing themselves. Constitutive patterns were: (a) value
      conflicts when students' values conflicted with academic behavioral values, and
      (b) on the fringe, when students felt isolation from the main student body, and
      open to attack (evaluation). Students struggled to be successful in their
      commitment to complete the degree, but often questioned the applicability of the
      program in their cultural setting. CONCLUSIONS: A more flexible supportive
      environment is needed to support students' goals to attain degrees, as well as to
      encourage dialogue on differing cultural values. Faculty who teach culturally
      diverse students may need to examine rigid behavioral standards that mandate an
      assertive practitioner persona and may be a barrier to attainment of goals.

PMID- 10887721
TI  - Nursing education at an art gallery.
AB  - PURPOSE: To introduce an experiential teaching-learning method in nursing
      education based on art gallery visits. Works of art communicate a broad spectrum
      of human experiences and thoughts, and can be useful when studying interpersonal
      relations. DESIGN: Theoretical framework on experiential learning was based on
      writings of Dewey and Burnard. Data were collected from nursing students (N =
      206) at a university college of health sciences in Sweden during a 3-year period,
      1995-1998. METHOD: The pedagogical approach was experiential and based on three
      phases: observation, conceptualisation, and reflection. When students visited the
      art gallery, they were encouraged to look for metaphoric expressions of
      interpersonal relations. Students were asked to interpret the art, report
      findings to fellow-students, and evaluate the program. FINDINGS: Studying works
      of art was a powerful teaching-learning method for understanding interpersonal
      relations. Students related interpretations of a work of art to interpersonal
      relations in nursing. CONCLUSIONS: Nursing students' observations and
      understanding of interpersonal relations were enhanced by the art gallery
      program.

PMID- 10887722
TI  - An instrument to measure professional nursing values.
AB  - PURPOSE: To describe the Nursing Professional Values Scale (NPVS), its
      development, reliability and validity, and its derivation from the Code of Ethics
      of the American Nurses Association. DESIGN: The NPVS was tested on 599 subjects,
      including baccalaureate and masters' students and practicing nurses. The students
      were enrolled in one of 25 programs selected at random from all NLN accredited
      programs in the United States. Practicing nurses were randomly selected from a
      State Board of Nursing list. METHOD: A 44-item, norm-referenced instrument with a
      Likert-scale format was tested. The responses of participants to this instrument
      were subjected to principal axis factor analysis with varimax rotation. FINDINGS:
      Eight factors were identified, accounting for 58% of the total variance. The two
      major factors were Caregiving and Activism. CONCLUSIONS: Initial results showed a
      high level of reliability and validity for the NPVS. The NPVS is a useful
      instrument for measuring professional nursing values and enhancing professional
      socialization.

PMID- 10887723
TI  - Community development and health in Canada.

PMID- 10887724
TI  - Nursing education and practice in Turkey.

PMID- 10887725
TI  - And what will we remember late in November?

PMID- 10887726
TI  - Sedation for delirium and other symptoms in terminally ill patients in Edmonton.
AB  - The use of sedation and the management of delirium and other difficult symptoms
      in terminally ill patients in Edmonton has been reported previously. The focus of
      this study was to assess the prevalence in the Edmonton region of difficult
      symptoms requiring sedation at the end of life. Data were collected for 50
      consecutive patients at each of (a) the tertiary palliative care unit, (b) the
      consulting palliative care program at the Royal Alexandra Hospital (acute care),
      and (c) three hospice inpatient units in the city. Patients on the tertiary
      palliative care unit were significantly younger. Assessments confirmed the more
      problematic physical and psychosocial issues of patients in the tertiary
      palliative care unit. These patients had more difficult pain syndromes and
      required significantly higher doses of daily opioids. Approximately 80% of
      patients in all three settings developed delirium prior to death. Pharmacological
      management of this problem was needed by 40% in the acute care setting, and by
      80% in the tertiary palliative care unit. The patients sedated varied from 4% in
      the hospice setting to 10% in the tertiary palliative care unit. Of the 150
      patients, nine were sedated for delirium, one for dyspnea. The prevalence of
      delirium and other symptoms requiring sedation in our area is relatively low
      compared to others reported in the literature. Demographic variability between
      the three Edmonton settings highlights the need for caution in comparing results
      of different palliative care groups. It is possible that some variability in the
      use of sedation internationally is due to cultural differences. The infrequent
      deliberate use of sedation in Edmonton suggests that improved management has
      resulted in fewer distressing symptoms at the end of life. This is of benefit to
      patients and to family members who are with them during this time.

PMID- 10887727
TI  - General practitioner training in palliative care: an experiential approach.
AB  - With the rising incidence of cancer and with more terminally ill patients wishing
      to be cared for at home, it is clear that there is a growing need for general
      practitioners (GPs) who are skilled in providing palliative care. In an attempt
      to improve the palliative care knowledge and skills of GPs in Western Australia
      and the quality of care they provide, a 14-week training program was developed by
      the Silver Chain Nursing Association and the Perth South Eastern Division of
      General Practice. The program used experiential learning techniques, such as a
      clinical attachment and mentoring. Research has shown that performance-based
      rather than cognitive education methods have a greater impact on practice
      outcomes. The program was evaluated by an external body and found to have
      achieved its objectives. The results of the evaluation are discussed, together
      with their implications for postgraduate education.

PMID- 10887728
TI  - Existential issues in palliative care--interviews with cancer patients.
AB  - A minority of terminally ill patients achieve a peaceful death. Many factors,
      including existential distress, contribute to the emotional disquiet of patients.
      This study focuses on the reactions of terminally ill cancer patients to
      questions concerning existential issues within the themes of meaning, relations,
      autonomy, guilt, dignity, and communication. The results of this study indicate
      that patients experience a number of problems dealing with existential issues,
      consider these questions important, and wish to be able to discuss these types of
      questions with someone.

PMID- 10887729
TI  - Transforming experience into wisdom: healing amidst suffering.

PMID- 10887730
TI  - Improve care and comfort: use the label "dying".

PMID- 10887731
TI  - Can the development of palliative care services meet the needs of people with
      HIV?

PMID- 10887732
TI  - Creativity and self-care for caregivers.

PMID- 10887733
TI  - Respiratory depression during methadone rotation in a patient with advanced
      cancer.

PMID- 10887734
TI  - Terminal illness and schizophrenia.

PMID- 10887735
TI  - Advancing motor neurone disease (MND)

PMID- 10887737
TI  - Submerging technology: hyperbaric medicine.

PMID- 10887736
TI  - Terminal cancer syndrome.

PMID- 10887738
TI  - Foundation is a 'lifesaver' to many uninsured. Physicians give free care to
      state's working poor.

PMID- 10887739
TI  - Iron overload and the heart.

PMID- 10887740
TI  - Preventing perinatal HIV: prenatal HIV testing and strategies to reduce the risk
      of maternal--fetal HIV transmission.

PMID- 10887741
TI  - Medical care for a major league baseball team: a team physician's perspective.

PMID- 10887742
TI  - Managing cerebral concussions: the Georgia Tech approach.

PMID- 10887743
TI  - Medical care of the Atlanta Hawks.
AB  - NBA players are among the best athletes in the world. Providing medical care for
      this elite group is a rewarding privilege. It requires a multidisciplinary
      approach emphasizing a carefully planned prevention program. When injuries occur,
      team physicians must provide an immediate accurate diagnosis and trainers must
      treat early and frequently to insure a rapid and successful return to sports.

PMID- 10887744
TI  - Sudden cardiac arrest in athletic medicine.

PMID- 10887745
TI  - The Georgia games--my experience.

PMID- 10887746
TI  - Medical care at the Super Bowl.
AB  - Although coordinating medical care at the Super Bowl is something that we look
      forward to and have a lot of fun doing, we take it very seriously and understand
      the importance of delivering medical care at what many people consider to be the
      greatest sporting event in the world. It is certainly one of the most watched and
      recognized events in the world and because of this, we attempt to set up a system
      that will allow for the best medical care available and standardization of this
      medical care through our experience within Medical Sports Group.

PMID- 10887747
TI  - Patella-femoral knee instability in a college basketball player.

PMID- 10887748
TI  - Medical aspects of professional hockey in Atlanta.

PMID- 10887749
TI  - We aren't Georgia or Georgia Tech yet, but watch out, we're growing!: the
      athletics program at Georgia State University.

PMID- 10887750
TI  - Plasma levels of cortisol, progesterone, oestradiol-17 beta and prostaglandin F2
      alpha metabolite after ACTH (Synacthen Depot) administration in ovariectomized
      gilts.
AB  - In order to elucidate the effect of stress on reproductive hormones, the present
      study was designed to investigate the effect of adrenocorticotropic hormone
      (ACTH) on the plasma levels of cortisol, progesterone, oestradiol-17 beta and
      prostaglandin F2 alpha metabolite in ovariectomized gilts. Ovariectomy and
      cannulation of the jugular vein were performed within 1 week of oestrous
      detection, under general anaesthesia. Approximately 1 week after surgery, two
      gilts were each administered ACTH (Synacthen Depot) intravenously, at a dose of
      0.01 mg/kg body weight, and one gilt was given saline solution (5 ml). The
      reverse was performed on the following day. The administration of ACTH was
      followed by a concomitant elevation of cortisol, progesterone and prostaglandin
      F2 alpha metabolite but not of oestradiol-17 beta. Peak cortisol, progesterone
      and prostaglandin F2 alpha metabolite levels were reached at 80 +/- 10.0, 80 +/-
      10.0 and 46.6 +/- 13.3 min after ACTH administration and the durations of the
      peaks were 181.8 +/- 19.8, 308.1 +/- 49.7 and 181.8 +/- 7.9 min, respectively.
      The total area under the curve for cortisol, progesterone and prostaglandin F2
      alpha metabolite was significantly higher in the ACTH than in the control group.
      The present results indicate that during stress, cortisol, progesterone and
      prostaglandin F2 alpha levels are elevated while the level of oestradiol-17 beta
      is less affected. It can be concluded that the administration of ACTH to
      ovariectomized gilts, results in the elevation of cortisol, progesterone and
      prostaglandin F2 alpha metabolite but not of oestradiol-17 beta.

PMID- 10887751
TI  - Effects of plant-induced hypervitaminosis D on cutaneous structure, cell
      differentiation and cell proliferation in cattle.
AB  - Solanum glaucophyllum (Sg) (synonym S. malacoxylon) is a plant toxic to cattle
      due to its high levels of 1,25-dihydroxyvitamin D3 as glycoside derivatives. Sg
      causes a disease characterized by wasting and calcification of soft tissues. The
      effects of vitamin D are not only important in calcium homeostasis, but also in
      immune regulation, cell growth and cell differentiation. Skin samples in Sg
      intoxicated and control heifers were studied histologically. Cellular
      differentiation and proliferation were analysed by immunohistochemical expression
      of cytokeratins, involucrin and proliferating cell nuclear antigen (PCNA). The
      results were obtained by image processing and analysis and were statistically
      evaluated. Sg-intoxicated cattle showed atrophy of epidermis and severe
      involution of hair follicles and of sebaceous and sweat glands. As judged by PCNA
      expression, cellular proliferation was reduced, even though the reduction was not
      statistically significant. The analysed markers of differentiation, e.g.
      involucrin and cytokeratins 10 and 11, changed in relation to Sg-poisoning. The
      possible pathogenesis of the skin lesions is discussed.

PMID- 10887752
TI  - Serum progesterone levels in post-partum dairy cows after repeated application of
      the prostaglandin F2 alpha analogue D (+) cloprostenol sodium.
AB  - Reproductive management programmes based on strategic use of prostaglandin F2
      alpha (PGF2 alpha) to induce and synchronize oestrus in post-partum dairy cows
      are widespread. Repeated shortening of the oestrous cycle during early lactation
      in high-yielding dairy cows, however, could impair corpus luteum function and
      thus decrease fertility. The objective of this study was to analyse the effect of
      repeated treatments with the prostaglandin F2 alpha analogue D (+) cloprostenol
      sodium on progesterone concentrations indicative of a functional corpus luteum in
      post-partum dairy cows. Furthermore, the influence of milk production, parity and
      endometritis on progesterone concentrations under these circumstances were
      studied. Eighty-four cows of a commercial dairy operation were treated three to
      four times with D (+) cloprostenol sodium (Preloban; Hoechst Roussel Vet,
      Wiesbaden, Germany) at 14-day intervals, starting 22-28 days post-partum. Blood
      samples were collected prior to treatment 1 (sample 1) and 14 days after
      treatments 1, 2 and 3 (samples 2-4) and serum progesterone (P4) levels were
      determined. The percentage of cows with P4 levels < 1 ng/ml decreased from 51% in
      sample 1 to 23% in samples 3 and 4. More primiparous cows had low P4 levels 14
      days after the second treatment than older cows (P < 0.05). Cows with low
      progesterone levels in sample 3 or 4 had lower protein contents in milk on the
      second milk test day post-partum and in their cumulative milk yield of the first
      100 days of lactation. Clinical endometritis at post-partum examination did not
      influence progesterone levels after treatment with PGF2 alpha. Repeated
      application of PGF2 alpha (more than twice) in the post-partum period does not
      influence serum progesterone levels 14 days after treatment. Failure to develop
      luteal tissue after treatment contributed to the conception failures after first
      service.

PMID- 10887753
TI  - Frequency of traumatic cow injuries in relation to housing systems in Swiss
      organic dairy herds.
AB  - A study was performed to estimate the extent of cow injuries as an indicator of
      animal welfare in organic dairy farms in Switzerland. The study was conducted
      during the winter feeding period of 1997/98 and was part of a larger project on
      animal health, nutrition and production in certified organic dairy herds in
      Switzerland. Potential predictors of injuries related to animal housing were
      quantified and relations between occurrence of injuries and nutritional status
      and production were evaluated. The investigation was designed as a cross
      sectional study and included a representative sample of 152 farms and 1856 cows.
      Every farm was visited once and each cow was scored for claw-, skin- and joint
      lesions and body condition. Statistical analyses were performed appropriate for a
      stratified and one-stage cluster sample weighted for the entire population of
      organic dairy farms in Switzerland. Possible individual and environmental
      predictors of cow injuries were analysed using multinomial logit models for
      ordinal outcomes. The overall frequencies of injuries were 10.4% for joint
      lesions, 12.8% for soft-tissue injuries and 3.6% for claw lesions. Most joint
      injuries (84.9%) were observed at the hock joint, 9.4% at the carpus and 3.1% at
      the knee joint. The analysis of the association between frequency of injuries and
      potential predictors revealed heterogeneous results and the risk profiles were
      different between the categories of injuries measured in the study. These
      observations support the assumption that variations in type and severity of
      injuries are due to specific differences of animal management, housing design and
      due to different characteristics of individual cows.

PMID- 10887754
TI  - The influence of restraint immobilization stress on the concentration qf
      bioamines and cortisol in plasma of Pietrain and Duroc pigs.
AB  - Forty-five Duroc (recognized as not susceptible to stress) and 34 Pietrain
      (susceptible to stress) pigs were subjected to immobilization stress in a prone
      position for 5, 15, 30 and 60 min. Plasma concentrations of epinephrine (E),
      norepinephrine (NE), dopamine (DA) and cortisol (C) were determined in response
      to restraint stress. The concentrations of E, NE and DA were different between
      the two strains of pigs (some significant interactions); the highest response was
      seen after 5 min of stress. The concentration of plasma C increased with duration
      of stress and there was a significant interaction between strain of animals and
      the time of stress. Our data substantiate the use of E, NE, DA and C as
      indicators of stress in swine as early as 5 min after exposure to the stressor.
      It is also shown that stress-susceptible Pietrain pigs had higher plasma
      concentrations of E, NE and DA than Duroc pigs.

PMID- 10887755
TI  - Disseminated mycoses in a dog by Paecilomyces sp.
AB  - We describe a case of canine mycoses initially diagnosed by clinical signs and
      enzyme-linked immunosorbent assay anti-fungal test, and later confirmed by the
      isolation of Paecilomyces sp. during the post-mortem examination. The fungus was
      isolated from lesions in the kidneys, mitral valve, abdominal aorta and vertebral
      discs. In this kind of process, it is important to identify the responsible agent
      early in order to make a study of anti-fungal susceptibility and establish
      effective treatment.

PMID- 10887756
TI  - Histamine in lambs with abomasal bloat, haemorrhage and ulcers.
AB  - The median concentration of histamine in abomasal fluid of lambs with abomasal
      haemorrhage and/or ulcers (group 2) was significantly (P < 0.05) higher than the
      concentrations in lambs presenting abomasal bloat (group 1) and in the healthy
      and the diseased controls. In group 2, there was also a strong correlation (R2 =
      0.81) between the histamine concentrations in abomasal tissue and abomasal fluid,
      although the median value of histamine in the abomasal tissue was not
      statistically higher in this group than in the others. The urine of lambs in
      group 2 also had numerically higher median concentration of histamine than the
      other groups. Five out of eight tested strains of Lactobacillus spp. and one out
      of two strains of Clostridium sordellii, isolated from abomasal contents of lambs
      with abomasal disease, were strong producers of histamine. Bacterial production
      is one possible source for the increased histamine concentrations in lambs
      suffering from abomasal haemorrhage and/or ulcers.

PMID- 10887757
TI  - Reactive and proactive aggression: evidence of a two-factor model.
AB  - This article examines the construct validity of reactive and proactive
      aggression, as assessed by the teacher-rating scale developed by K. A. Dodge and
      J. D. Coie (1987). In Study 1 (n = 149 boys), confirmatory factor analyses
      revealed that a 2-factor model, in which a substantial correlation was observed
      between the 2 latent factors, presented a better fit than a single-factor model.
      Study 2 (n = 193 boys) examined the relations presented by the 2 forms of
      aggression with peer status, leadership, social withdrawal, and victimization by
      peer. Reactive and proactive aggressive behaviors presented distinct patterns of
      relations consistent with the theoretical definitions. The results of these
      studies suggest that the questionnaire measures 2 forms of aggressive behavior
      that, although being substantially related, have a unique discriminant dimension.

PMID- 10887758
TI  - Development and validation of the Eating Disorder Diagnostic Scale: a brief self
      report measure of anorexia, bulimia, and binge-eating disorder.
AB  - This article describes the development and validation of a brief self-report
      scale for diagnosing anorexia nervosa, bulimia nervosa, and binge-eating
      disorder. Study 1 used a panel of eating-disorder experts and provided evidence
      for the content validity of this scale. Study 2 used data from female
      participants with and without eating disorders (N = 367) and suggested that the
      diagnoses from this scale possessed temporal reliability (mean kappa = .80) and
      criterion validity (with interview diagnoses; mean kappa = .83). In support of
      convergent validity, individuals with eating disorders identified by this scale
      showed elevations on validated measures of eating disturbances. The overall
      symptom composite also showed test-retest reliability (r = .87), internal
      consistency (mean alpha = .89), and convergent validity with extant eating
      pathology scales. Results implied that this scale was reliable and valid in this
      investigation and that it may be useful for clinical and research applications.

PMID- 10887759
TI  - Use of the Personality Assessment Inventory to assess psychopathy in offender
      populations.
AB  - The authors investigated the validity of the Antisocial Features (ANT) scale of
      the Personality Assessment Inventory (PAI; L. C. Morey, 1991) with respect to
      assessments of psychopathy in 2 offender samples. Study 1 included 46 forensic
      psychiatric inpatients who were administered the Screening Version of the Hare
      Psychopathy Checklist (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995). In
      Study 2, 55 sex offenders were administered the Hare Psychopathy Checklist-
      Revised (PCL-R; R. D. Hare, 1991). ANT scores correlated highly with the PCL:SV
      total score (r = .54) and moderately with the PCL-R total score (r = .40). ANT
      tapped primarily behavioral symptoms of psychopathy rather than interpersonal and
      affective symptoms. Also, ANT had low to moderate diagnostic efficiency regarding
      diagnoses of psychopathy, suggesting that it may be better used as a dimensional
      rather than categorical measure of this construct.

PMID- 10887761
TI  - Detection of coached general malingering on the MMPI-2.
AB  - The current study examined the effects of validity-scale coaching on one's
      ability to feign general psychopathology. College students were coached on
      malingering strategies and completed the MMPI-2. Their responses were compared
      with students asked to malinger psychopathology without validity-scale coaching
      and with psychiatric inpatients completing the MMPI-2 under standard
      instructions. In accordance with previous research (e.g., J. R. Graham, D. Watts,
      & R. E. Timbrook, 1991), uncoached malingerers were adequately discriminated from
      patients by using the Infrequency (F) scale. However, as suggested by previous
      research (R. Rogers, R. M. Bagby, & D. Chakraborty, 1993), the F scale was not as
      effective at classifying coached malingerers. It was found that other validity
      indicators, such as the Infrequency Psychopathology Scale were more accurate at
      discriminating between coached malingerers and hospitalized patients.

PMID- 10887760
TI  - Psychometric properties of the Hawaiian Culture Scale--Adolescent Version.
AB  - This article reports on the psychometric properties of a newly constructed
      Hawaiian Culture Scale--Adolescent Version. A total of 2,272 Native Hawaiian and
      1,170 non-Hawaiian adolescents were administered this 50-item inventory that
      measures the source of learning the Hawaiian way of life, how much Hawaiian
      beliefs are valued and important to maintain, how much non-Hawaiian beliefs are
      valued, Hawaiian blood quantum, and specific cultural traditions (seven subscales
      = Lifestyles, Customs. Activities, Folklore, Causes-Locations, Causes-Access, and
      Language Proficiency). The results strongly supported the internal consistency
      and validity of the measures for both the Hawaiian and non-Hawaiian groups. On
      the basis of the demographic data, partial support was offered for cross-cultural
      theories of ethnic identity. More consistent support was found for
      multiculturalism in Hawai'i's adolescents. Further research is needed to link
      these measures with indicators of psychological adjustment (e.g., depression,
      anxiety, substance use).

PMID- 10887762
TI  - A taxometric analysis of MMPI-2 Infrequency scales [F and F(p)] in clinical
      settings.
AB  - The typology of overreporting, which is a deliberate attempt to amplify symptoms,
      simulate psychopathology, or understate coping capacities, was examined using
      taxometric procedures with Minnesota Multiphasic Personality Inventory-2 (MMPI-2)
      Infrequency scales [F and F(p)] in psychiatric inpatient and Veterans Affairs
      (VA) medical center treatment settings. Overreporting was identified as a taxon
      using several taxometric procedures, and the multiple estimates of the taxon base
      rate were consistent within each sample. Mean base-rate estimates were .27 and
      .19 for the psychiatric inpatient and VA medical center settings, respectively.
      Overall classification rates ranged from .80 to .97 across the 2 settings, which
      supports the use of F and F(p) in the identification of overreporting on the MMPI
      2 in psychiatric inpatient and VA medical center settings.

PMID- 10887763
TI  - Structural differences in parent and child reports of children's symptoms of
      depression and anxiety.
AB  - Two cohorts of public elementary school children and their parents (assessed 3
      years apart) completed child and parent forms of the Children's Depression
      Inventory (CDI) and the Revised Children's Manifest Anxiety Scale (RCMAS).
      Assessments were conducted twice, once during the fall (N = 562) and again during
      the spring (N = 630) of the 6th grade. Factor analyses revealed 3 factors for
      each measure. Two of the 3 parent CDI factors manifested some degree of
      congruence with their counterparts from the child CDI. Similarly, 2 of the 3
      RCMAS factors were somewhat congruent across informant types. Differences between
      parent and child factor structures suggest that parents' and children's reports
      focus on somewhat different aspects of child psychopathology, and they can make
      qualitatively different contributions to the multiaxial assessment of children.

PMID- 10887765
TI  - Supplementary WMS-III tables for determining primary subtest strengths and
      weaknesses.
AB  - It is common practice to evaluate the age-adjusted subtest scores from the
      Wechsler intelligence scales to determine strengths and weaknesses within a
      profile. The Wechsler Memory Scale-III (WMS-III; D. Wechsler, 1997a) represents a
      significant improvement over its predecessors and, for the first time, provides
      age-adjusted subtest scores for interpretation, just as the Wechsler intelligence
      scales have done for 60 years. It is reasonable to assume that examiners will
      evaluate the WMS-III subtest profiles for strengths and weaknesses. However, the
      WMS-III Administration and Scoring Manual and the WAIS-III-WMS-III Technical
      Manual (The Psychological Corporation, 1997) provide no assistance for
      accomplishing this goal. Data from the WMS-III standardization sample, as
      described in the WAIS-III-WMS-III Technical Manual, were used to develop tables
      for determining both confidence levels and infrequency of differences between
      individual subtest scores and the means of 5 subtest combinations that may be
      clinically relevant for individual cases.

PMID- 10887764
TI  - Use of the AUDIT and the DAST-10 to identify alcohol and drug use disorders among
      adults with a severe and persistent mental illness.
AB  - State Psychiatric Hospital outpatients (93 men, 69 women) diagnosed with a
      serious persistent mental illness (SPMI) completed the Alcohol Use Disorders
      Identification Test (AUDIT) and Drug Abuse Screening Test (DAST-10) by interview
      as part of a general health/behavior screening instrument. Responses to the AUDIT
      and DAST-10 were compared with criteria of current diagnosis and occurrence of
      symptoms in the last year for both alcohol and drug use disorders, respectively.
      Results showed that for both diagnosis and symptoms, AUDIT cutpoints of 7 and 8
      had good sensitivity and specificity, and DAST-10 cutpoint of 2 was identified
      for both criteria. These and other findings suggest that both instruments have
      promising clinical utility when used with individuals diagnosed with an SPMI.

PMID- 10887766
TI  - Validation of a brief measure of posttraumatic stress disorder: the Distressing
      Event Questionnaire (DEQ).
AB  - The Distressing Event Questionnaire (DEQ) is a brief instrument for assessing
      posttraumatic stress disorder (PTSD) according to criteria provided in Diagnostic
      and Statistical Manual of Mental Disorders (4th ed.). The DEQ possesses high
      internal consistency and exhibited satisfactory short-term temporal stability in
      studies with Vietnam War combat veterans and battered women. In a sample of
      Vietnam War veterans and 4 separate samples of abused women (with histories of
      incest, rape, intimate partner abuse, or prostitution and abuse), the DEQ
      exhibited very good discriminative validity when judged against structured
      interview assessment of PTSD. The DEQ exhibited strong convergent validity with
      other PTSD measures and other indexes of adjustment and also exhibited strong
      convergent validity as a measure of PTSD across ethnic groups in both the veteran
      sample and the combined women's sample.

PMID- 10887767
TI  - Development and preliminary validation of a brief broad-spectrum measure of
      trauma exposure: the Traumatic Life Events Questionnaire.
AB  - This article describes the development and preliminary validation of a brief
      questionnaire that assesses exposure to a broad range of potentially traumatic
      events. Items were generated from multiple sources of information. Events were
      described in behaviorally descriptive terms, consistent with Diagnostic and
      Statistical Manual of Mental Disorders IV posttraumatic stress disorder stressor
      criterion A1. When events were endorsed, respondents were asked if they
      experienced intense fear, helplessness, or horror (stressor criterion A2). In
      separate studies with college students, Vietnam veterans, battered women, and
      residents of a substance abuse program, most items possessed adequate to
      excellent temporal stability. In a study comparing questionnaire and structured
      interview inquiries of trauma history, the 2 formats yielded similar rates of
      disclosure. Preliminary data on positive predictive power are also presented.

PMID- 10887768
TI  - [Olfaction dysfunction].
AB  - OBJECTIVE: To report of results obtained with the systematized boarding
      (physiopathology, diagnosis and treatment) to dysfunction of the smell that can
      affect the patient's life in significant form. MATERIAL AND METHOD: 58 patients
      were evaluated that went to the clinic with alterations in the olfaction or the
      pleasure, or both. The protocol includes a guided questionnaire, tests of
      identification of scent and threshold olfactory, rhinomanometry, nasal histogram,
      I simple study radiological of the roads breathing superiors and paranasals
      sinus, besides computer axial tomography and endoscopy. RESULTS: The most
      frequent cause in the olfactory dysfunction was the due mechanical obstruction to
      inflammatory processes, as chronic sinusitis and nasal polyposis, which obstruct
      the olfactory niche like complication; of the 58 patients, 48% belonged to this
      group. This inflammatory illness was divided, in turn, in allergy pure 25%,
      infectious 21% and pattern mixed 54%. The olfactory tests showed hyponia severe.
      In the general analysis the rest of the olfactory dysfunction was classified as
      postviral in 20%, posttraumatic in 12.1%, a group miscellaneous 8.6%, caused by
      toxins 6-9%, being a group of idiopathic cause in 3.4%.

PMID- 10887769
TI  - [Hereditary Osler angioedema (report of case)].
AB  - A case of Osler's hereditary angioedema, that show a halimark of aedema of
      facing, neck, hands and foots, respiratory difficulty, to feel sick, to vomit,
      diarrhoea and abdominal pain, from the seven years old.

PMID- 10887770
TI  - [Economic study on asthma in Mexico].
AB  - OBJECTIVE: The objective of this study is to establish to cost of bronchial
      asthma in the budget for a Clinic-Hospital with a closed population and to learn
      about our achievements in controlling that illness, as well as our weaknesses and
      areas of opportunity. Another objective is to compare our results with similar
      studies in other countries. METHOD: In 1998, the Clinic Nova of Monterrey had a
      fixed population of 28,394 persons who receive the complete range of medical
      services, including hospitalization and drugs from the pharmacy. The prevalence
      of asthma in our clinic is 2.6%, direct and indirect costs were obtained
      according to the Biostatistics Department, Operative Control and Emergencies.
      RESULTS: In 1998, the total cost of bronchial asthma was: 1,624,765.00 pesos. The
      direct cost of asthma was 1,582,735.00 pesos (97% of the total) and out of this,
      the cost of medications was 1,131,575.00 pesos (71% of the direct costs) and
      42,030.00 pesos in indirect costs only represented 3% of the total. CONCLUSION:
      Our results indicate that the greatest cost lies in the purchase of medication
      for ambulatory patients. The costs for hospitalization and visits to the
      emergency room only represented 10% of the total and, for that reason, our most
      important conclusion is that the physicians at Clinica Nova are using the
      preventive anti-inflammatory schemes recommended at present. This has helped to
      reduce the most important direct cost, hospitalization.

PMID- 10887771
TI  - [Degree of skin hypersensitivity as possible indicator of severity of asthma in
      the atopic subject].
AB  - AIMS: Many factors have been involved in the determination of bronchial asthma
      severity, among which are: Family history, atopic condition and environmental
      factors. OBJECTIVE: To evaluate if the degree of skin test reactivity is an
      useful indicator of bronchial asthma severity in atopic subjects. MATERIAL AND
      METHODS: In a prospective design, 140 patients with allergic bronchial asthma
      were included. The degree of skin reactivity was measured by intradermal reaction
      to 54 common allergens, it was classified in four groups according to the
      positive test percentage. The patients were followed during one year, and the
      frequency of symptoms and exacerbations, tolerance to exercise, nocturnal asthma,
      frequency and type of required medication were registered. The pulmonary function
      was evaluated by espirometry and plethysmography every 6 months. Asthma severity
      was classified according to the GINA criteria (Global Initiative for Asthma) and
      drugs requirements. The results were analyzed with descriptive statistics and
      Spearman correlation, stratification by age groups was carried out. RESULTS: Mean
      age was 25.57 +/- 12.12 years, 59% were female patients. Intermittent asthma was
      present in 42% of the subjects, mild persistent asthma in 31%, moderate
      persistent asthma in 18% and severe persistent asthma in 9%. The degree of skin
      test reactivity was < 25% in 26 patients, 25-50% in 60 patients, 51-75% in 36 and
      > 75% in 15. There was not correlation between skin test reactivity and asthma
      severity in the total population. In the stratified analysis there was
      significant correlation in the group of 5-15 years (p < 0.05) but with a low
      predictable value. CONCLUSIONS: The skin test reactivity degree was not an useful
      indicator of the asthma severity in this study.

PMID- 10887772
TI  - [Risk factors in child asthma].
AB  - OBJECTIVE: To evaluate six risk factors in a population of low economic level.
      MATERIAL AND METHOD: 40 asthmatic children were studied, 21 masculine and 19
      feminine, with a 9.3 years old half age +/- 3.22 years. A group control is
      included (22 children) without asthma and without allergic symptoms. RESULTS: I
      intragroup study. In the control group the tobacco atmosphere overcame the
      prospective frequency (p < 0.05), circumstance that didn't happen to the group of
      patient. Intragroup studies. There were not significant differences among the
      parameters studied in both groups, except for the frequency of family
      antecedents. CONCLUSIONS: The genetic factor is decisive for the initial asthma.
      The genotypic studies has found the chromosomic locus that regulate their
      expression. The environmental factors, particularly the tobacco pre and
      postnatal, they are decisive in the early precipitation of the beginning of the
      asthma.

PMID- 10887773
TI  - [Use of pentoxifylline in pediatric patients with grade IV (OMS) lupus
      nephropathy who have received multiple treatments].
AB  - AIMS: Systemic Lupus Eritematosus is an autoimmune disease, the incidence in
      pediatric poblation in about 5%, and until 90% develop nephropathy. MATERIAL AND
      METHOD: Included patients with lupic nephropathy grade IV (OMS) ages between 0
      and 16 years old, multitreated, who administrated PTX. We take samples before
      treatment, during, and 4 month after, evaluating renal function and hepatic
      function. RESULTS: For female, tow male, promedium age 14.1 years old. Poteinuria
      get a significative p = 0.0012; hematuria was lowering its levels, While immune
      circulating complex, get too a significative p = 0.0050. In creatinine inverse
      showed an important modification of its pending. CONCLUSIONS: This results
      demonstrates, that PTX in nephritis lupic patients, helps to brake the habitual
      deterioration in renal function. Includes more patients for a long time of
      treatment, we'll get better results than this.

PMID- 10887774
TI  - Progress towards poliomyelitis eradication, Myanmar, 1996-1999.

PMID- 10887775
TI  - Vibrio parahaemolyticus, Japan, 1996-1998.

PMID- 10887776
TI  - Acute viral hepatitis, Japan. April-December 1999.

PMID- 10887777
TI  - Forensics in NP practice.

PMID- 10887778
TI  - Should childless NPs cover?

PMID- 10887779
TI  - Understanding civil trials, Part 2.

PMID- 10887780
TI  - Ties that bind. Mothers, daughters and sons continue to feel effects of DES.

PMID- 10887781
TI  - Gender gap. Women and coronary heart disease.

PMID- 10887782
TI  - Pain management in HIV-positive patients.

PMID- 10887784
TI  - Patient information. Understanding vaginal infections.

PMID- 10887783
TI  - Reframing menarche education. A developmental perspective.

PMID- 10887785
TI  - The politics of prevention. Issues in emergency contraception.

PMID- 10887786
TI  - Somewhere in between. An overview of perimenopause.

PMID- 10887787
TI  - Achieving breastfeeding success. Simple solutions to common concerns.

PMID- 10887788
TI  - Empowering nurse practitioners. Through individual leadership.

PMID- 10887789
TI  - Under control. Managing asthma and diabetes in pregnancy.

PMID- 10887790
TI  - Behind closed doors. Detecting and responding to marital rape.

PMID- 10887791
TI  - A role beyond primary care.

PMID- 10887792
TI  - Ten resolutions for the New Year.

PMID- 10887793
TI  - Seniors sharing medication.

PMID- 10887794
TI  - Legislative roundup for 1999.

PMID- 10887795
TI  - Slow and steady wins the race. Arthritis and diabetes drugs made a difference in
      1999.

PMID- 10887797
TI  - Patient information. Handwashing guide.

PMID- 10887796
TI  - When personal turns political. This year's health headlines focused on topics
      traditionally taboo.

PMID- 10887798
TI  - Antiplatelet agents in acute coronary syndromes. Safety, patient selection are
      key concerns.

PMID- 10887799
TI  - The varicella vaccine. Inching toward universal use.

PMID- 10887800
TI  - The rewards of going solo.

PMID- 10887801
TI  - Competency-related pay: how will nurses be judged?

PMID- 10887802
TI  - Modernizing standards in mental health nursing.

PMID- 10887803
TI  - Professional misconduct case studies. Case 14: Breach of trust. Occupational
      health nurse who perverted the course of justice.

PMID- 10887804
TI  - A new standard for the nursing assessment of leg ulcers.
AB  - In the UK, the majority of patients with leg ulcers are treated by nurses in the
      community. Nurses are central to the diagnosis and management of these patients.
      Formal clinical assessments are not always conducted; where they are, there is
      not always compliance or access to Doppler ultrasound scanners, or training in
      the necessary skills and techniques. Assessment should be routine and systematic;
      an understanding of why each observation is required will aid compliance. This
      article includes a review of the current requirements for assessment and sets out
      a minimum standard. This has been devised with the practicalities of community
      nursing and of nurse accountability in mind.

PMID- 10887805
TI  - Breast screening and ethnic minority women: a literature review.
AB  - The incidence of breast cancer is reported to be low among ethnic minority women.
      However, the number of women diagnosed with breast cancer in this group is
      expected to rise over the next decade, as a result of changes in lifestyle and
      environmental factors. Despite the introduction of the NHS Breast Screening
      Programme in 1988, the uptake of breast cancer screening services remains low
      among minority women. The main reasons identified for this low uptake are a lack
      of knowledge among women from the ethnic communities about screening services and
      a lack of referral/recommendations by healthcare professionals and physicians.
      Future initiatives need to target appropriate education strategies for healthcare
      professionals on the needs of ethnic groups, as for many women this will be their
      first point of contact within the screening programme.

PMID- 10887806
TI  - Meningitis: causes, symptoms and signs and nursing management.
AB  - This article discusses the infectious disease meningitis--a notifiable disease
      since 1912 (Payling, 1994). The major concern is bacterial meningitis and in
      particular the meningococcal cause. Viral meningitis is also considered. Some 50%
      of cases of meningitis in the UK are of the viral kind, where the patient usually
      makes a full recovery and in some instances may not be aware of having contracted
      the disease (Payling, 1994). Cases of bacterial meningitis are few and if treated
      effectively and with urgency can result in full recovery; however, any delay may
      result in fatal sequelae. Bacterial meningitis occurs mainly as a result of
      meningococcal, pneumococcal or Haemophilus influenzae type B (Hib) infection. The
      latter has largely been eradicated in England and Wales as a result of effective
      immunization programmes. The nurse must develop an awareness of the disease, and
      diagnose it at an early stage. He/she should know the procedures for referring
      the patient to prevent an escalation of the infection and to reduce the severity
      of its effects.

PMID- 10887808
TI  - Radiation-induced skin reactions. 3: Evaluating the RISRAS.
AB  - This article, the last in a three-part series, reports the methods used to
      evaluate the Radiation-induced Skin Reaction Assessment Scale (RISRAS), along
      with the results. For a newly developed tool, the results of the elementary
      reliability and validity testing were satisfactory. The RISRAS could be used in
      clinical practice following revision and further development and its introduction
      into clinical oncology practice is recommended as it will improve the assessment
      process of radiation-induced skin reactions and lead to better care for those
      patients undergoing radiotherapy. In the first article in the series (Vol 8(17):
      1134-40), the extensive nature of radiotherapy-induced skin reactions were
      reported, along with their significance for the patient undergoing radiotherapy.
      Previously described assessment scales were examined in preparation for the
      development of the RISRAS. In the second article (Vol 8(18): 1208-11), the need
      for holistic yet specific assessment of these reactions was demonstrated and the
      methods used to develop the RISRAS were described.

PMID- 10887807
TI  - Family views of a paediatric outpatient nursing development unit.
AB  - This article reports on one aspect of the quinquennial evaluation of a King's
      Fund accredited nursing development unit (NDU) within a paediatric outpatient
      department of a large district general hospital during the period 1993-1998. The
      study draws upon descriptive data obtained through a parental satisfaction
      survey. Overall the results demonstrate a high degree of satisfaction with the
      outpatient visit family experience and suggest that the status of NDU has helped
      the children's outpatient department become more responsive to the needs of
      families.

PMID- 10887809
TI  - Legal aspects of NHS direct and walk-in clinics.
AB  - Two innovations in health care, NHS Direct and walk-in clinics, both designed to
      improve patient access, have been introduced by the Government. NHS Direct was
      one of the first NHS innovations introduced by the present Government and has
      been operating, on a restricted basis, for about 18 months. The Department of
      Health recently announced the setting up of more direct access clinics run by
      nurses, to which any person can go for assistance and advice on health care. This
      article considers the legal implications of these innovations.

PMID- 10887810
TI  - Innovations in bandage technology: SSL's non-fray Steripaste.
AB  - After centuries of use in wound management the healthcare industry continues to
      improve the medicated paste bandage. This article focuses on Steripaste, a well
      known medicated zinc paste bandage from SSL International, that has a new non
      fray edge to minimize the incidence of fibres being shed onto the wound.

PMID- 10887811
TI  - Confidentiality. 9: The law relating to whistle blowing.
AB  - Alex Black, a staff nurse on an intensive care unit, was extremely concerned
      about the lack of adequate staffing levels on the unit. He had put his concerns
      in writing to his manager, but no action appeared to have been taken. On one
      weekend there was such a lack of staff that it was impossible to ensure that one
      nurse was attending every patient on a ventilator at all times. A young girl,
      injured in a road accident, was brought into the unit following surgery, and was
      placed on a ventilator. Alex was asked to monitor her care as well as that of
      another patient being ventilated. The girl died and Alex considered that this
      might not have happened if there had been adequate staff levels. He knows that
      the family are ignorant of how low the standards of care were and is anxious that
      they should be notified. Would it be lawful for him to tell them?

PMID- 10887812
TI  - Preparing nurses to work effectively in the prison environment.
AB  - Nurses who go to work in prisons begin their new career without having had any
      specific preparation for this unique and diverse role. The demands placed upon
      nurses are unlike any they will have experienced in their previous clinical
      posts. The work of a nurse in prison contains elements of both mental health
      nursing and practice nursing. The context in which this nursing occurs means that
      the nurse is presented with complex clinical and professional dilemmas.
      Consequently, few nurses start to work within this specialty with all of the core
      competencies required to be clinically effective and confident in their role.
      This article describes how this unmet educational need was addressed by the
      development of a diploma level module.

PMID- 10887813
TI  - Nurses must educate the public about their work.

PMID- 10887814
TI  - Prison nurses need more educational support.

PMID- 10887815
TI  - Nurses must take the lead in critical care.

PMID- 10887816
TI  - Professional misconduct case studies. Case 15: Abuse of position. Borrowing money
      from a patient's relative and failing to repay it.

PMID- 10887817
TI  - The importance of wound documentation and classification.
AB  - Good wound documentation has become increasingly important over the last 10
      years. Wound assessment provides a baseline situation against which a patient's
      plan of care can be evaluated. A number of documents have been implemented
      including the 'Code of Professional Conduct for Nurses, Midwives and Health
      Visitors' (UKCC, 1992), the 'Post-registration Education Project' (UKCC, 1997),
      'Standards of Records and Record Keeping' (UKCC, 1998), and 'Keeping the Record
      Straight' (NHS Executive (NHS E), 1993). These documents require nurses to
      maintain their professional knowledge and competence, and to recognize any
      deficiency in their knowledge. Having recognized any deficiency they should read
      the relevant literature and/or attend a study day on wound care. Nursing records
      are the first source of evidence investigated when a complaint is made. Wound
      assessment is very complex and a standardized approach to evaluation needs to be
      adopted. Such evaluation should encompass colour classification, wound
      measurement, and classification of tissue type present in the wound. There are
      numerous methods of measuring wounds; these range from the simple, such as manual
      estimation by means of a ruler or wound tracing, to the more technical
      procedures, e.g. computer, image analysis, and colour imaging using hue
      saturation and intensity. Photography, in conjunction with nursing notes,
      provides a very good form of wound documentation and can provide clear evidence
      if required for legal cases.

PMID- 10887818
TI  - The benefits of non-invasive ventilation and CPAP therapy.
AB  - There is increasing recognition of the therapeutic benefits of applying non
      invasive ventilation in the treatment of acute and chronic respiratory failure.
      Continuous positive airway pressure (CPAP) therapy is now commonly used in the
      treatment of patients who have problems with oxygenation but not ventilation on
      acute respiratory wards. The focus of this article will be on the development of
      non-invasive ventilation techniques and CPAP therapy and the benefits and
      indications for its use in respiratory medicine. The suggestions for monitoring
      these patients will be examined and the potential hazards will be identified.
      This will be considered in relation to the evolution of non-invasive respiratory
      care units and the establishment of an acute respiratory care unit (ARCU).

PMID- 10887819
TI  - COPE: towards a comprehensive assessment of caregiver need.
AB  - Supporting family carers is a common policy objective across Europe. However, if
      appropriate help is to be provided there is a need for a sensitive assessment
      process. This article describes the COPE project, the purpose of which is to
      develop a first-stage assessment tool that can be used to identify carers
      requiring a further in-depth consideration of their support needs.

PMID- 10887820
TI  - Pulmonary embolism: an overview of treatment and nursing issues.
AB  - Pulmonary embolism presents with a vague clinical picture. Pathophysiological
      effects vary from small pulmonary infarcts to life-threatening cardiogenic shock.
      Therefore, radiological investigation to confirm the diagnosis is required to
      institute appropriate treatment. This ranges from heparin therapy to surgical
      embolectomy. Care of this patient group requires vigilant nursing, because of not
      only the risk of further embolic episodes, but also the potential serious
      complications of treatment. Prevention of venous thromboembolism can be
      pharmacological or mechanical. The proactive role that nurses take in prevention
      of this potentially fatal disease process is often overlooked by the medical
      literature.

PMID- 10887821
TI  - Job satisfaction and employment prospects for nurses.
AB  - A recent media campaign has emphasized the benefits to the NHS of attracting
      nurses back to work. In this article, the potential for success from such a
      recruitment drive is acknowledged but the balance of assessment is redressed, to
      reflect a broader economic perspective which takes into account resource
      limitations. The costs of these initiatives, as well as the benefits, are
      considered in terms of how else the resources involved could be used. A call is
      made for nurses, and other individual decision makers engaged in nurse
      recruitment, to consider benefits with all relevant costs systematically, even if
      reliable information is limited. That approach would be in the spirit of the
      changes to NHS governance that are currently being introduced and could help to
      ensure that the health of patients overall is served as well as possible by the
      contribution to it made by nurses.

PMID- 10887822
TI  - Reflective practice and guided discovery: clinical supervision.
AB  - This article explores the parallels between reflective practice as a model for
      clinical supervision, and guided discovery as a skill in cognitive psychotherapy.
      A description outlining the historical development of clinical supervision in
      relationship to positional papers and policies is followed by an expose of the
      difficulties in developing a clear, consistent model of clinical supervision with
      a coherent focus; reflective practice is proposed as a model of choice for
      clinical supervision in nursing. The article examines the parallels and processes
      of a model of reflection in an individual clinical supervision session, and the
      use of guided discovery through Socratic dialogue with a depressed patient in
      cognitive psychotherapy. Extracts from both sessions are used to illuminate the
      subsequent discussion.

PMID- 10887823
TI  - Confidentiality. 10: Child care and the duty of confidentiality.
AB  - Jane told Angela White, a paediatric staff nurse, that she was being abused by
      her father, but did not want anyone to be told. Jane was 14 years old,
      intelligent and mature for her age. What is the law?

PMID- 10887824
TI  - Clinical evaluation of an electronic pressure-relieving mattress.
AB  - A 12-month clinical evaluation of the Talley Quattro Deep Cell 2000 mattress
      manufactured by Talley Medical was undertaken on both a trauma and surgical ward
      at the Royal Devon and Exeter Hospital. An identified registered nurse
      coordinated the evaluation with support from tissue viability clinical nurse
      specialists. Data on patients, including diagnosis, Waterlow score, pressure area
      condition and general comments by nurses and patients, were collected. The
      evaluation involved 35 patients who were at high- to very-high risk of pressure
      sore formation. The results showed that 16 out of 40 sores healed during the
      evaluation period and 16 sores remained unchanged. Only one patient developed
      broken skin while nursed on the mattress. Seventeen patients maintained tissue
      integrity. Although the study was limited the results suggest that the Talley
      Quattro Deep Cell 2000 mattress is useful in preventing and managing pressure
      sores in high- to very high-risk patients.

PMID- 10887825
TI  - Nurses face the same problems worldwide.

PMID- 10887826
TI  - Nurses must not become substitute doctors.

PMID- 10887827
TI  - Mental health and cancer: is there a missing link?

PMID- 10887828
TI  - Professional misconduct case studies. Case 17: Respecting the dignity of
      patients. Nurse who showed a video film containing dubious material.

PMID- 10887829
TI  - A critical evaluation of the use of nutrition screening tools by nurses.
AB  - Malnutrition remains a problem in hospital and community patients, the
      consequences of which have deleterious effects on the sick individual and cost
      implications for healthcare providers. Provision of nutritional support has been
      shown to improve patient outcome in those at risk of malnutrition; therefore, the
      detection and treatment of malnutrition is paramount. Nurses have been identified
      as being in an ideal position to carry out routine nutritional screening to
      detect patients at risk of malnutrition and hence refer to the dietitian for
      detailed nutritional assessment and provision of nutritional support. Therefore,
      many nutritional screening tools have been developed to guide nurses in basic
      nutritional screening. However, for a tool to be effective certain criteria must
      be met including ease of use, cost-effectiveness, the presence of an action plan
      and prior testing for validity, reliability, sensitivity and specificity. Six
      such tools are critically evaluated in this article to establish whether they
      meet these criteria. Surprisingly, none of the screening tools demonstrated a
      beneficial effect on clinical outcome or met all of the above criteria. It is
      therefore essential that these tools are refined and retested before becoming
      part of established nursing practice.

PMID- 10887830
TI  - I.v. devices and related infections: causes and complications.
AB  - The use of intravenous devices has long been established as a life-saving and
      important part of total patient management. However, such devices are not without
      risk and their use is frequently complicated by local or systemic infections and
      complications. Twenty-five million patients are estimated to enter the NHS
      annually and receive some form of intravenous therapy by the peripheral route
      (Campbell, 1998). It behoves all staff who are involved in the management of
      intravenous devices to base their practice on what is agreed by consensus in the
      literature as being effective in reducing the risk of hospital-acquired
      infections. This article draws together such literature and presents
      recommendations for good practice for the management of intravenous-related
      devices.

PMID- 10887831
TI  - Autonomy and the developing role of the clinical nurse specialist.
AB  - The role of the clinical nurse specialist has developed in response to social,
      technological and political changes that have impacted upon the delivery of
      health care. Nursing has traditionally been associated with femininity and in a
      paternalistic health structure the concept of nursing care can be devalued
      because autonomous nurses may threaten the balance of power. Autonomy is a multi
      faceted concept and yet, if nurses have the courage to embrace both the
      traditional values of nursing and the expertise that their caring role brings to
      health care, they will be able to develop their own competence and autonomous
      practice. Nurses may not need autonomy in order to enhance their roles but they
      do need to concentrate on the concept of care as a team phenomenon. This notion
      is included in the UKCC's higher level of practice initiative which may direct
      specialist practice in the future. A negative element to nurse specialization is
      that nursing care can become fragmented, thus compromising the continuity and
      accountability of patient care.

PMID- 10887832
TI  - Implications of nursing role expansion for professional practice.
AB  - The topic of nursing role expansion has caused much heated debate in the nursing
      press in recent years. The contemporary relevance of the debate is heightened by
      the current recruitment and retention crisis in nursing, and continued pressures
      to reduce junior doctors' hours and workload. This article re-examines the
      'expanded role debate' by putting current concerns in an historical framework.
      The perceived benefits of role expansion are discussed, and balanced against
      continued concerns expressed by practitioners regarding possible detrimental
      effects on care delivery. The potential erosion of 'caring' as the heart of
      nursing practice is acknowledged, and challenges are made to the belief that
      nursing has the 'monopoly on caring'. The issue of 'nursing time', perhaps the
      major barrier to continued role expansion, is also explored. The future division
      of labour within healthcare delivery is seen as pivotal to this aspect of the
      debate, and a pragmatic vision for the future is offered. Finally, the issue of
      the paucity of the evidence base underpinning role expansion is considered and a
      plea is made for future developments to be soundly underpinned by research.

PMID- 10887833
TI  - Nurses' accountability in relation to nurse-led services.

PMID- 10887834
TI  - Migraine: helping clients choose treatment and identify triggers.
AB  - Migraine is a common complaint causing untold difficulties or aggravation for the
      sufferer. Clients with migraine can have very real fears of possible pathologies
      and the nurse is in a strong position to dispel these fears with information and
      reassurance. This article discusses information and knowledge which nurses can
      use to enable clients to take control over their migraine: from the range of
      choices about treatment to the identification of triggers that precipitate
      migraine or identification of factors to inhibit attacks. Treatments may be broad
      ranging from non-pharmacological to pharmacological approaches, which may be
      either symptomatic or prophylactic. Pharmacological treatments are presented in
      detail indicating the range of types from analgesia to antidepressants.

PMID- 10887835
TI  - Total bed management: the way forward in pressure sore prevention.
AB  - King's College Hospital, London, is the first trust to implement total bed
      management (TBM) to assist in the reduction and prevention of pressure sores. TBM
      is a new concept, whereby the tissue viability, manual handling and therapy needs
      of the trust are met at reduced costs through a partnership with a contractor.
      The introduction of a large number of electric bed frames and foam mattress
      replacements, with the availability of dynamic pressure-relieving equipment and a
      service agreement, has led to an expected trust saving of 86,000 Pounds in
      1998/1999 and 100,000 Pounds in 1999/2000 onwards. This article outlines the
      perceived benefits of this approach.

PMID- 10887836
TI  - Reflection demystified: answering some common questions.
AB  - There is a growing body of literature related to reflection. However, few authors
      address how to reflect at a practical level. This article aims to answer some of
      the more common questions about reflection: What is reflection about? What is its
      value for nursing practice? What skills are needed to be a reflective
      practitioner? Where to start? There are doubts concerning the effectiveness of
      reflection and there is little research evidence regarding its benefits. Despite
      this, it is argued that reflection has the potential to raise nurses' awareness
      of practice.

PMID- 10887837
TI  - Protecting patients by questioning doctors.

PMID- 10887838
TI  - Age discrimination should be outlawed in the NHS.

PMID- 10887839
TI  - Children need protecting in death as well as life.

PMID- 10887840
TI  - Professional misconduct case studies. Case 18: Sexual harassment. Nurse who
      sexually harassed staff during teaching sessions.

PMID- 10887841
TI  - Understanding physiology of wound healing and how dressings help.
AB  - One of the most fascinating features of the human body is its ability to repair
      damaged tissue. When the skin is injured a complex process occurs. The natural
      healing process can be divided into four distinct stages: inflammatory,
      granulation, epithelization and maturation. This process can take up to 2 years.
      Brunner and Suddarth (1992) classified wound healing into three stages: primary;
      secondary; and tertiary. Many factors affect how long a wound will take to heal,
      e.g. concurrent illnesses, nutritional status and the dressing used. A holistic
      approach to wound care is the key, and if all the factors are not addressed then
      wound healing will not prevail.

PMID- 10887842
TI  - Evaluation of an Australian miscarriage support programme.
AB  - Miscarriage is a frequent and distressing event for women who often require
      admission to a gynaecology unit for the evacuation of the products of conception.
      Most women are admitted for day surgery or an overnight stay. The short time
      frame limits the time nursing staff have to provide support and information for
      women who have experienced loss through miscarriage. This article presents the
      qualitative evaluation of a telephone follow-up service provided as part of the
      Miscarriage Support Programme of Care conducted by staff of the gynaecology
      inpatient services in an Australian public hospital. The data from this
      evaluation indicate that miscarriage does have a varying degree of impact on a
      woman's inpatient experience and emotional recovery. The primary themes of
      emotional recovery, support after discharge, inpatient experience of care, and
      usefulness of the literature given to women before discharge, will guide the
      ongoing development of support and discharge planning by staff of gynaecology
      inpatient services for women who have experienced miscarriage.

PMID- 10887843
TI  - Achievements in child health over the first half of the 20th century.
AB  - This article will reflect upon the gains made in the health and welfare of
      children in the UK over the first half of this century. It will discuss how
      government reforms covering health, welfare and education have improved all
      aspects of children's lives and the contribution made by the relatively new
      professions of nursing, midwifery and health visiting. Finally, it will show how
      changing attitudes towards children and the two World Wars culminated in
      international recognition of children's rights. A future article will highlight
      the increasing rate of change seen in the second half of this century.

PMID- 10887844
TI  - Integrated care pathways: an audit tool in paediatric oncology.
AB  - The families of children undergoing treatment for cancer encounter many
      professionals with varying levels of training, experience and competency. This
      can lead to variance in the care and advice they receive. The aim of the audit
      described in this article was to improve care for children with fever and
      neutropenia by introducing an integrated care pathway. Guidelines for neutropenia
      were examined and a retrospective analysis of notes undertaken to study what was
      happening before a pathway was introduced. From this, standards were set and a
      pathway developed which was introduced to all members of the oncology unit and
      implemented as part of the children's care. This article will also focus on the
      audit and evaluation of the pathway. Following this, the pathway has been changed
      to reflect care and can now be used to introduce new evidence or research in this
      field.

PMID- 10887845
TI  - Gerontological nursing. 1: Challenges nursing older people in acute care.
AB  - This article, the first in a series of five, will briefly trace the emergence of
      gerontological nursing and highlight some of the tensions that currently exist in
      the context of acute care environments. The next two articles will consider the
      prospects and challenges for nurses working with older people in community and
      nursing home environments, while the fourth article uses hearing impairment
      across a range of care contexts as a case study to summarize the ways in which
      the nursing contribution to the health needs of older people could be
      significantly improved. The series will conclude with an article drawing together
      the challenges that gerontological nursing faces in the new millennium.

PMID- 10887846
TI  - Universal precautions: improving the knowledge of trained nurses.
AB  - Universal precautions relate to the management of blood-borne viruses such as
      human immunodeficiency virus (HIV) and hepatitis B and C. Advice on the
      transmission of blood-borne viruses and the precautionary measures used to reduce
      or eliminate cross-infection have been addressed by national and professional
      bodies. There is a significant amount of research which assesses trained nurses'
      knowledge of universal precautions and includes understanding of the transmission
      routes of blood-borne viruses and the measures required to prevent cross
      infection. However, the majority of the literature indicates an incomplete
      knowledge among trained nurses of the principles and application of universal
      precautions. The ability of the trained nurse to fulfil his/her role as health
      educator, teacher and therefore effective infection control practitioner is
      questioned by the literature. This article discusses the role of education in
      improving the knowledge of trained nurses and considers the implementation of in
      service training and preregistration education.

PMID- 10887847
TI  - Healthcare practitioners' perceptions of clinical guidelines.
AB  - This article gives an update on developments in the field of clinical guidelines
      with particular reference to guidelines issued by the General Medical Council and
      the Clinical Negligence Scheme for Trusts. It also focuses on a recent academic
      study on healthcare professionals' perceptions of clinical guidelines (Cotton and
      Sullivan, 1999) and introduces the National Guideline Clearing House which is
      based in the USA.

PMID- 10887848
TI  - Confidentiality. 12: The problems posed by suicide and euthanasia.
AB  - Jenny White, a hospice nurse, is caring for Peggy who is in the terminal stages
      of motor neurone disease. Peggy lives at home and is cared for by her husband
      John with support from the community health team and social services. John
      confides to Jenny that he has promised his wife that when her suffering becomes
      unbearable he will help her to end her life. Afterwards, John says he will have
      no further desire to continue life alone. Should Jenny respect the confidential
      nature of this information?

PMID- 10887849
TI  - Medilan: a hypoallergenic lanolin for emollient therapy.
AB  - Lanolin has been used for thousands of years for its emollient properties. For
      the past two decades it has had an ill-deserved reputation as an important
      sensitizer. Medilan is an ultra-purified hypoallergenic medical grade lanolin
      that has been shown to cause almost zero sensitization. As well as its occlusive
      properties it has also been shown to penetrate the skin and help to store water
      in the stratum corneum. The hypoallergenic nature of Medilan combined with its
      soothing and hydrating properties make it a valuable ingredient in emollient
      preparations used to treat eczema and other dry skin conditions.

PMID- 10887850
TI  - Spirituality and being a 'friend of the patient'.

PMID- 10887851
TI  - Systematic review of ondansetron for the prevention and treatment of
      postoperative nausea and vomiting in adults.
AB  - OBJECTIVES: To determine the efficacy and safety of ondansetron for the
      prevention and treatment of postoperative nausea and vomiting (PONV) in adults.
      DESIGN: Systematic review of published double-blind randomised controlled trials.
      DATA SOURCES: Twenty seven trials from 1990 to July 1998 retrieved from a
      systematic literature search (Medline, Cinahl, Embase, Cochrane Library,
      reference lists, hand searching of anaesthetic journals, & provided manufacturer
      information); restricted to English language. MAIN OUTCOME MEASURES: Estimation
      of efficacy (incidence of complete absence of nausea or other outcome measure as
      defined by the authors) at 24 hours. RESULTS: Seven double-blind randomised
      controlled trials with 1,623 patients studied intravenous ondansetron 1 mg, 4 mg,
      or 8 mg for the treatment of postoperative nausea and vomiting (PONV). Four mg,
      compared with metoclopramide 10 mg, produced higher patient satisfaction scores
      and an increased incidence of freedom from nausea at 24 hours. Further studies
      are required to compare the safety, efficacy and dose response with other anti
      emetics at 24 hours. Twenty double-blind randomised controlled trials with 4,364
      patients studied intravenous and oral administration of ondansetron 1 mg, 4 mg,
      and 8 mg for the prevention of postoperative nausea and vomiting. There appears
      to be no significant difference between droperidol (0.625 mg, 1 mg or 1.25 mg)
      i.v. and ondansetron 4 mg in efficacy and incidence of side effects. Compared
      with metoclopramide, ondansetron produced less nausea but the incidence of
      vomiting was the same at 24 hours. CONCLUSIONS: Further PONV could be prevented
      with ondansetron 4 mg compared with placebo and metoclopramide 10 mg. Further
      studies are required to compare ondansetron with other anti-emetics for the
      treatment of PONV. For prophylaxis of PONV ondansetron 4 mg appears to be equal
      to low dose droperidol in efficacy and the incidence of side effects, and
      superior to metoclopramide. Ondansetron should perhaps be limited to second line
      treatment in view of patient satisfaction, efficacy and cost when compared with
      droperidol.

PMID- 10887852
TI  - Introduction of common pay terms and conditions for theatre staff.

PMID- 10887853
TI  - Organ donation. 2. Consent and patient rights.

PMID- 10887854
TI  - A common pay spine.

PMID- 10887855
TI  - Alison Bell Memorial Award 1999. Reflection on perioperative practice: when is it
      right to say no?

PMID- 10887856
TI  - The named nurse in the perioperative setting.

PMID- 10887857
TI  - Back to basics. Patient assessment in recovery.
AB  - The immediate post-anaesthetic period is a particularly vulnerable time for
      patients, fraught with risk from dangerous complications. Recovery staff play a
      vital role in the ongoing, continuous assessment of patients at this period in
      their operative experience, and must be skilled in detecting and preventing the
      onset of serious, sometimes life-threatening events. Vigilant recovery care can
      assist in ensuring ward staff receive an awake, stable and comfortable patient
      who has been cared for in an atmosphere where safety and comfort are of paramount
      concern.

PMID- 10887858
TI  - Learning to give and accept research critiques: some unique models.

PMID- 10887859
TI  - Parent satisfaction with education, support, and decision-making regarding their
      children's central venous access devices.
AB  - This descriptive, exploratory study assessed parents' satisfaction with the
      education and support they received before and after their children had central
      venous access devices (CVADs) inserted for cancer treatment. Decisions regarding
      the type of CVAD and parent satisfaction with that choice were also evaluated.
      Parents of children who experienced a CVAD during the six-year period 1992-1997
      participated. Data were collected through telephone interviews using a
      questionnaire specifically designed for the purposes of the study. Results
      suggest that parents were satisfied with the teaching and support received both
      prior to and following CVAD insertion. Other findings reveal that not all parents
      take part in decisions about the type of device used, and that if given a choice,
      based on their experience, they would likely choose implanted ports over Hickman
      catheters.

PMID- 10887860
TI  - Cancer treatment-induced menopause: meaning for breast and gynecological cancer
      survivors.
AB  - Many cancer survivors are faced with irreversible changes resulting from cancer
      treatment. One such change some women face after cancer is treatment-induced
      menopause. Eight women (four with breast and four with gynecological cancers)
      were interviewed to explore the impact of treatment-induced menopause on their
      lives. Results indicated that participants' understanding and coping with
      menopause occurred within the larger context of the total cancer experience. For
      some of the women, menopause was not a significant problem; for others, the
      symptoms caused major distress and were a continuing reminder of the losses
      suffered due to cancer. Important concerns for all participants were: taking and
      keeping control, the desire to return to "normal" after cancer, and maintaining a
      coherent sense of self. Strong statements were also made about the power of
      knowing and the power of support in coping with treatment-induced menopause.
      Findings are discussed with implications for nursing practice.

PMID- 10887861
TI  - Information needs in the early detection phase of colorectal cancer.

PMID- 10887862
TI  - A partnership to improve continuity of care for terminally ill persons in the
      community.

PMID- 10887863
TI  - Alternative therapies: a challenge for researchers.

PMID- 10887864
TI  - Behavioral responses of newborns of insulin-dependent and nondiabetic, healthy
      mothers.
AB  - The purpose of this study was to compare the behavioral responses of term
      newborns of insulin-dependent diabetic mothers (NDMs) with newborns of
      nondiabetic, healthy mothers. The research design involved matched controls with
      repeated measures. Participants included 40 NDMs matched with 40 newborns of
      nondiabetic, healthy mothers. The main outcome measures were the seven dimensions
      of the Neonatal Behavioral Assessment Scale (NBAS) and the modal response score.
      The results showed that NDMs performed significantly poorer than their matched
      controls on motor processes and reflex functioning. For all newborns, motor
      processes, autonomic stability, reflex functioning, and the modal performance
      score were better on Day 2 than Day 1. It was concluded that although NDMs'
      behavioral responses improved by Day 2, their overall pattern of responses could
      be described as listless or sluggish. Due to their poorer motor and reflex
      responses, NDMs may require increased efforts to facilitate sensitive maternal
      responding during their first days of life.

PMID- 10887865
TI  - The relationship between method of pain management during labor and birth
      outcomes.
AB  - This study examined the relationship between method of pain management during
      labor and birth outcomes. A retrospective comparative chart review of 233
      primiparous deliveries was conducted and group assignment was based on method of
      pain control (nonnarcotic, narcotic, or epidural). Epidural analgesia or
      anesthesia was associated with increased rates of instrumental and cesarean
      delivery. Augmentation of labor using a synthetic oxytocin was reported in more
      charts than expected, and the length of the second stage of labor was longer in
      those who received epidural analgesia or anesthesia. Apgar scores for those who
      received early epidural analgesia or anesthesia were lower than for those who
      received late or no epidural analgesia or anesthesia, although Apgar scores were
      satisfactory across all groups. Between-groups differences were unrelated to time
      of epidural placement or maternal temperature. Findings are relevant for maternal
      child nurses who serve as a resource for families wishing to make informed
      decisions about pain management in labor.

PMID- 10887866
TI  - A comparison of fatigue and energy levels at 6 weeks and 14 to 19 months
      postpartum.
AB  - It has been assumed that women recover from pregnancy and childbirth within 6
      weeks. Recent research shows that women's fatigue levels are the same, or higher,
      at 6 weeks postpartum as at the time of delivery. This study determined the
      differences in primiparous women's fatigue and energy levels at 6 weeks and 14 to
      19 months postpartum. Determinations of how some contributing factors and
      outcomes of postpartum fatigue relate to each other and to fatigue and energy at
      14 to 19 months postpartum were also made. Analyses revealed that women are more
      fatigued and less energetic at 14 to 19 months than they were at 6 weeks
      postpartum. Quality of sleep did not correlate with fatigue or energy. At 14 to
      19 months postpartum return to full functional status is almost complete, with
      household and infant care responsibilities being most complete. The women were
      experiencing mild life crises of various sorts, were somewhat depressed, and were
      gratified in the mothering role.

PMID- 10887867
TI  - Nurses' knowledge of pain assessment, pharmacologic and nonpharmacologic
      interventions.
AB  - This study compared differences in knowledge of pain assessment and pharmacologic
      and nonpharmacologic pain management strategies among 232 L.P.N.s and R.N.s from
      three hospitals. Twenty-three adult medical, surgical, and special care units
      were represented. The "Knowledge of Pain Management" tool measured knowledge of
      pain assessment, drug and nondrug strategies, and was based on AHCPR guidelines.
      Scores ranged from 24% to 92%. There were significant differences in scores
      across hospitals and between R.N.s and L.P.N.s. The mean score was 72% for
      L.P.N.s and 75% for R.N.s. There was a significant difference in pharmacologic
      scores between L.P.N.s versus A.D./A.A.-R.N.s, B.S.N-R.N.s, and M.S.N.-M.S.-R.N.s
      but not between L.P.N.s and diploma-R.N.s. There were significant differences in
      overall knowledge scores between L.P.N.s versus B.S.N.-R.N.s but not A.D./A.A.
      R.N.s, diploma-R.N.s, and M.S.N./M.S-R.N.s. Finding suggest the need for
      aggressive nursing education programs offered in academic and clinical settings
      to assist nurses in effectively managing the universal phenomenon of pain.

PMID- 10887869
TI  - The influence of background clinical data on infant pain assessments.
AB  - The purpose of this study was to determine the importance of knowledge of
      clinical background data on nursing assessments of infant pain. In a quasi
      experimental design, the infant pain assessments of two groups of pediatric
      nurses were compared. Both groups assessed the levels of pain of the same
      videotaped infants. One group also read clinical background data about each
      infant; the other group did not. The group who read clinical background data
      evidenced higher mean levels of assessed pain per videotaped infant than did the
      group who only viewed the videotapes. Findings underscore the importance of
      clinical data and clinical context in the process of assessing infant pain and
      the risk of underestimating pain when all factors are not considered.

PMID- 10887868
TI  - Impact of an instructional program on nurses' accuracy in capillary blood glucose
      monitoring.
AB  - This experiment examined the accuracy of capillary blood glucose monitoring using
      the visual glucose oxidase strip (Chemstrip) procedure. Also, the effects of a
      certification program for nurses on the accuracy of glucose oxidase strip
      monitoring by registered nurses were analyzed. Seventy nurses and 123 patients
      participated. Data were collected from nurses' recordings of visual Chemstrip
      procedure results and from the concurrent laboratory blood glucose determinations
      for 3 months. The data included 70 Chemstrip recordings and 70 concurrent
      laboratory blood glucose recordings in the experimental group and 68 Chemstrip
      and 68 concurrent laboratory glucose recordings in the control group. Data
      analysis revealed that the accuracy of the nurses' performance of the glucose
      oxidase strip procedure was inadequate. A certification program did, however,
      dramatically improve the accuracy of the procedure. Proximity of time between the
      certification program and the performance of the glucose oxidase strip procedure
      did not affect accuracy.

PMID- 10887870
TI  - Talk of the millennium.

PMID- 10887871
TI  - Measuring infant exposure to environmental tobacco smoke.
AB  - Methods to measure infant exposure to environmental tobacco smoke (ETS) are
      needed to identify infants at highest risk for ETS-related health problems. The
      purpose of this study was to validate measures sensitive to changes in levels of
      infant exposure to ETS and to develop a predictive model of infant exposure to
      ETS. Fifteen infants of smoking mothers were followed from birth to 6 weeks of
      age. Exposure to ETS was measured by using a smoking habits questionnaire,
      cigarette "butt" collection, infant urine nicotine and cotinine levels, and
      ambient nicotine (personal air monitors). The 24-hour cigarette butt collection
      was the best predictor of acute (adjusted r2 = .83) and chronic exposure
      (adjusted r2 = .47) measured by infant urinary nicotine and cotinine levels when
      the infants were 2 weeks of age. Including scores on the smoking habits
      questionnaire and ambient nicotine levels increased the adjusted r2 to .88 and
      .61, respectively.

PMID- 10887872
TI  - Skin protection and breakdown in the ELBW infant. A national survey.
AB  - The purpose of this study was to learn how neonatal intensive care unit (NICU)
      nurses describe the problem of skin breakdown in the extremely low birth weight
      (ELBW) infant, examine interventions currently used to prevent and treat ELBW
      infant skin breakdown, and to learn how nurses describe and measure skin
      breakdown. Questionnaires were sent to 482 NICUs in the United States, and a
      response was requested from a registered nurse with at least 2 years NICU
      experience currently employed in the NICU who regularly managed ELBW infants.
      Questionnaires were returned from 215 NICUs (45%). Analysis revealed that an
      average of 21% of ELBW infants suffered skin breakdown during the 1st week of
      life. Nurses who reported the least problems with ELBW infant skin breakdown
      followed skin-care protocols that limited use of tape and made liberal use of
      Aquaphor to protect fragile skin. Recommendations from this study include the
      development of an objective tool to rate skin breakdown and further study of
      product efficacy used in the treatment of skin breakdown.

PMID- 10887873
TI  - Changing clinical practice through research: the case of delirium.
AB  - Promoting application of study findings to the clinical setting is a constant
      challenge for nurse researchers. This project used change theory to include staff
      RNs in a research study on delirium and to use relevant findings. The research
      hypothesis was: Staff nurses who use a standardized protocol will have improved
      ability to identify delirium in elderly hospital patients. Staff nurses on the
      intervention unit used this protocol to screen for delirium on all consenting
      inpatients 75 years of age and over, and control unit nurses continued using
      their standard assessment practices. Intervention unit nurses demonstrated an
      improved ability to identify the presence and absence of delirium, and
      voluntarily requested to continue using the protocol after the study was
      terminated. Use of a theoretical model to include nurses in the study promoted
      the successful conduct of the research and subsequent use of findings.

PMID- 10887874
TI  - Falls in a community of older adults: putting research into practice.
AB  - This study described the incidences of falls and injuries related to those falls
      in a community of older adults. It used a convenience sample of 220 older adults
      in a continuing care retirement community. Over a 2-year period, all residents
      who had a witnessed or reported fall were evaluated by a nurse or nurse
      practitioner and completed a Falls Data form. There were 154 falls, most of which
      occurred between noon and midnight, within the residents' apartments, when
      walking (63%) or transferring (19%). Only 16 (10%) of the falls resulted in a
      fracture. The number of falls was the only variable associated with having an
      injurious fall. Individuals who had atrial fibrillation or neurological problems,
      were not married, and did not adhere to a regular exercise program were more
      likely to have multiple falls. The findings were used by the nurse practitioner
      to educate residents about falls in their community and to develop interventions
      to decrease the risk and incidences of falls.

PMID- 10887875
TI  - Pain, analgesic use, and morbidity in appendectomy patients.
AB  - Pain has immunosuppressive effects among the critically and chronically ill, and
      opioids may immunomodulate pain's deleterious effects. However, little is known
      about the relations between acute pain, acute illness, and morbidity among
      previously healthy surgical patients. This study retrospectively examined these
      relations in appendectomy patients (N = 61). Eleven patients (18%) had morbidity,
      with atelectasis (11.5%) the most frequent complication. There were no
      differences between those patients with and without morbidity and pain intensity,
      method of opioid administration, and total opioid dose. Patients who received
      nonopioid analgesics received fewer opioids, less preemptive analgesia, and had
      less morbidity, whereas patients whose appendixes perforated received higher
      opioid doses and received more preemptive analgesia. Although the relations
      between acute pain, opioid use, and morbidity among previously healthy surgical
      patients are unclear, findings infer that clinical practice does not follow
      guidelines advocated by analgesic experts.

PMID- 10887876
TI  - Patient-controlled analgesia: optimizing the experience.
AB  - A patient-controlled analgesia (PCA) program was established on a surgical unit
      with children age 7 years and older. The primary objectives for the PCA program
      were safety and efficacy. A retrospective evaluation of the first 30 patients
      enrolled in the program suggested in the program suggested that it was safe and
      adequately controlled pain for all but 4 patients. A chart review of these
      patients indicated that the relation between the number of failed administration
      attempts, the total hourly analgesic intake, and the pain intensity score was key
      to optimizing the use of PCA. Recommendations to strengthen the PCA program were
      implemented based on information gained from these 4 patients with poorly
      controlled pain.

PMID- 10887877
TI  - Paradoxes, puzzles and passing time.
AB  - Whilst technology and our understanding about the world has improved, I suspect
      that in many ways, the hopes, fears, worries, joy and love we feel are not so
      different from that of our ancestors of 500 or 700 years ago, though the social
      circumstances may have altered. We have beliefs and dreams and daily routines in
      our lives and many people hang onto age old superstitions without really knowing
      their origins, e.g. crossing our fingers for luck, touching wood, throwing salt
      over a shoulder or reading about star signs. The night sky also looks different
      to 1000 years ago. When we look up at the stars we see an image of the past in
      the present: the light we see set off from its origin long before the advent of
      antibiotics, the Russian Revolution or the first man on the moon. As we move
      forwards, the benefits of modern medicine and improvements in social and
      environmental issues (compared to just 100 years ago) have, paradoxically,
      provided us with a quality of life that allows us to live longer and gain a
      greater insight into the world around us. There is an opportunity to reflect and
      wonder at the healers of the early middle ages and of the way in which we wish
      medicine to develop. When reflecting about the past 1000 years, patterns begin to
      emerge of times past, epochs of healing and revolutions in the way we perceive
      myriad aspects of health and healing. I am sure there are ways of combining
      ancient ways with modern thinking, of blending art and science, of balancing
      logic and rationality with love, fun, humour and empathy. Of building on
      experience, so that caring is spiritually therapeutic, freeing our patients and
      ourselves as we move into the future and the new millennium.

PMID- 10887878
TI  - Government plans to regulate voluntary and private healthcare.
AB  - A recent Government consultation document has recommended proposals to
      dramatically extend protection for patients in the private sector. It has invited
      comments on whether these proposals should be extended to the complementary
      medicine sector. The provision include the creation of a new regulatory body,
      quality assurance mechanisms and a new complaints system. The lack of coherence
      within complementary medicine means that there has been very little consultation
      with therapists or their professional bodies. This article outlines the main
      proposals and calls for the creation of a pan-professional organization to assume
      trade union functions to ensure that in future complementary therapists gain a
      political voice over matters which directly affect their practice.

PMID- 10887879
TI  - Increasing diabetic self-care through guided imagery.
AB  - BACKGROUND: Findings from the literature and clinical practice describe the
      various strategies necessary on a regular basis to control blood sugar levels in
      people with diabetes and suggests that guided imagery techniques aid clients in
      adhering to the rigorous diabetic routine. METHODS AND RESULTS: An imagery script
      was developed and used to aid diabetic clients in maintaining their diabetic
      regimen. Participants in this cognitive experience indicated that the motivation
      script used with them by health-care practitioners was effective. The major
      treatment areas were blood testing, regular exercise, weight management, and
      consumption of a restricted lifetime diet. Several of these areas showed
      modification after the use of guided imagery.

PMID- 10887881
TI  - Report and reflection on the First Inter-continental Conference of Nurse Healers.

PMID- 10887880
TI  - The whole person in health care (with approaches from a perspective of mind-body
      medicine): a personal view.
AB  - This paper offers a brief mind-body view of: What the whole person is The four
      aspects of life: physical, emotional, mental, subtle energy states. The concept
      that health and wellbeing is analogous to developing musical harmony between the
      four aspects. Each aspect can be imagined as a musical note. When in balance the
      harmony between the notes is clear. When out of balance the effect is discordant.
      Ways that personal performance may be enhanced by the integration of these four
      aspects including self help approaches, mindful bodywork and energetic medicines.
      'When we are whole, we shall be healed...' (Caroline Stevensen).

PMID- 10887882
TI  - The relationship between health promotion and complementary therapies.
AB  - The underlying philosophies of health promotion and complementary therapies are
      very closely related and, consequently, share many similarities; yet such
      similarities that exist between these two disciplines are rarely expressed,
      acknowledged or explored. It would be almost impossible to practice complementary
      therapies without incorporating elements of health promotion within them, whether
      this is done so knowingly, or not, by the practitioner. This account sets out to
      establish the nature of such a relationship and highlights the common advantages
      and dilemmas in recognizing such a relationship. It seeks to determine the
      validity of closer collaboration (between the two disciplines) in order to
      provide a collective consensus for like-minded nurses to move towards a more
      holistic and empowering paradigm. It concludes by suggesting that, in order to
      move the shared aims of health promotion and complementary therapies forward,
      closer ties need to be established, between the disciplines, and built upon.

PMID- 10887883
TI  - Introduction to a therapy.
AB  - LCA is a remarkable educational tool to demonstrate to people the effects
      positive or negative that nutrition has on the body. They say that a picture is
      worth a thousand words and viewing your own blood on the TV monitor certainly
      gets one thinking. It can help motivate your patients to participate in healthier
      lifestyle choices that will dramatically affect their sense of well-being. I also
      tell my patients that anything they do now to positively affect their lives is
      like an investment in a retirement fund. As difficult as it may be to make those
      changes now, or to find the money to save now, the benefits will be reaped much
      later in life and appreciated more greatly. It is also clear that there is a need
      for greater research into this topic using RCT approaches and perhaps articles of
      this type will stimulate further enquiry.

PMID- 10887884
TI  - Age effects on long-term neuropsychological outcome in paediatric traumatic brain
      injury.
AB  - In order to investigate the relationship between age at injury and long-term
      neuropsychological impairment, 29 children and adolescents who sustained
      traumatic brain injury (TBI) were studied at least 6 years post-trauma. Tests of
      intellectual, memory, visuospatial and frontal lobe functions were administered
      to patients and 29 normal matched control subjects. Correlations between
      performance on neuropsychological tests and age showed the following direction:
      the younger the child when TBI was sustained, the worse the cognitive outcome.
      After controlling for injury severity, visuospatial functions remained related to
      age. Patients' performance differed significantly from that of controls in half
      of the neuropsychological variables analysed. To further investigate the effects
      of age at injury, the sample was divided in two groups (TBI before and after age
      of 8) and then compared with their respective controls. Patients damaged earlier
      presented impaired intellectual and visuospatial functions. The results suggest
      that neuropsychological sequelae remain after at least 6 years of evolution, and
      that there is an age at injury effect.

PMID- 10887885
TI  - Long-term mortality trends in patients with traumatic brain injury.
AB  - Comparison of long-term mortality rates between patients with traumatic brain
      injury (TBI) and the general population has not been adequately investigated.
      This project aimed to obtain information on the long-term mortality rate of
      patients with TBI. Using a rehabilitation database of a major teaching hospital,
      the search identified 476 patients, of whom 27 were deceased. This mortality rate
      (5.7%) was compared with the expected mortality rate for an equivalent population
      without TBI (1.5%) using Australian Life Table data. It was found that patients
      with TBI had a significantly higher mortality rate than the general population
      (chi2 = 12.2, p < 0.001). Possible reasons for this finding are discussed.

PMID- 10887886
TI  - Psychiatric treatment outcome following traumatic brain injury.
AB  - The relationship between self-reported history of traumatic brain injury (TBI)
      and psychiatric treatment outcome was investigated. TBI was hypothesized to be
      frequent, associated with cognitive deficits on neuropsychological testing, and
      less amenable to standard psychiatric treatment. Subjects were 42 psychiatric
      patients with a self-reported history of TBI and 25 psychiatric patients with no
      TBI history. Subjects received approximately 2 weeks of inpatient psychiatric
      treatment. Subjects received neuropsychological testing and completed the Brief
      Symptom Inventory weekly. TBI was frequent (66% of subjects); multiple injuries
      were common. Neuropsychological performance was generally average in both groups
      with few group differences. Subjects, on average, reported significantly
      decreased psychiatric symptoms on discharge. However, the TBI group appeared to
      improve less than the control group; group status was a significant predictor of
      treatment outcome. Implications of results for assessment and treatment of
      psychiatric disorders in patients with a history of TBI are discussed.

PMID- 10887887
TI  - The rehabilitation of attention in individuals with mild traumatic brain injury,
      using the APT-II programme.
AB  - Traumatic brain injury (TBI) is a prevalent cause of cognitive impairments and
      dysfunctions and affects over 2 million individuals each year. Mild traumatic
      brain injury (MTBI) is generally defined by a brief loss of consciousness, and
      post-traumatic amnesia that lasts for less than 24 hours. One region of the brain
      that is likely affected in patients with MTBI is the pre-frontal cortex. This
      region mediates several functions, including those required for adequate
      attention. Three individuals, diagnosed with MTBI and difficulties with
      attention, volunteered to participate in the study. Individuals were presented
      with 10 weeks of cognitive retraining with the Attention Process Training-II (APT
      II) programme, followed by 6 or 7 weeks of educational and applicational
      programmes. Cognitive tests were administered both pre- and post-training to
      assess the effectiveness of the programme. Analysis of the results showed that
      the APT-II programme improved attention and performance speed in each of the
      three individuals. In addition, any rehabilitated cognitive skills remained
      stable in each individual in the absence of the rehabilitation programme for at
      least 6 weeks.

PMID- 10887888
TI  - Awareness of deficits: emotional implications for persons with brain injury and
      their significant others.
AB  - The relationship between emotional distress and differing perceptions of the
      extent of deficits was investigated with fifty individuals with brain injury and
      their significant others. Participants completed questionnaires assessing their
      perceptions of the individual's deficits in various areas (Patient Competency
      Rating Scale, PCRS). Difference scores were used as markers for awareness of
      deficits. Emotional distress of the individuals with brain injury and their
      significant others was assessed with the Beck Depression Inventory (BDI) and the
      Beck Anxiety Inventory (BAI). Forty per cent of persons with brain injury and 34%
      of significant others reported symptoms suggestive of mild or greater depression,
      while 54% of persons with brain injury and 39% of significant others reported
      symptoms suggestive of experiencing mild or greater anxiety. Significant
      relationships were not found between the emotional distress of significant others
      and difference scores. Moderate-to-weak relationships were found between
      difference scores and the emotional distress of individuals with brain injury.
      The relationship between chronicity and awareness of deficits was in the opposite
      direction than predicted. The adjustment of significant others appears to be a
      function of the extent to which they perceive a resolution of deficits, time
      since injury, and other factors. Implications for rehabilitation and future
      research are discussed.

PMID- 10887889
TI  - Relationship between cognitive capabilities and social participation among people
      with traumatic brain injury.
AB  - This study attempts to determine the relationship between cognitive capabilities
      and social participation, over a 1-year period, among people who have experienced
      traumatic brain-injury (TBI). Using the Disability Creation Process as a basis
      for making hypotheses, three research questions were examined: (1) Do cognitive
      capabilities improve over time?; (2) Does social participation improve over
      time?; and (3) Are these two concepts related over time? The results and their
      clinical implications on rehabilitation are discussed, along with the limitations
      of this study.

PMID- 10887890
TI  - The effects of traumatic brain injury on reporting and responding to causal
      relations: an investigation of sensitivity to reinforcement contingencies.
AB  - Impairments in judging and responding to consequences that follow behaviour are
      often attributed to changes in various cognitive processes. An alternative
      conceptualization is that impairments may produce a reduction in sensitivity to
      reinforcement contingencies. The present investigation employed a methodology
      commonly used in research on judgements of causality to examine the effects of
      TBI on sensitivity to reinforcement contingencies. Participants were non-injured
      control subjects and adults with TBI. The experimental task required subjects to
      press a response key under a series of concurrent response-reinforcer
      contingencies that periodically delivered money for responding and not
      responding. Afterwards, subjects provided a judgement about each response
      reinforcer contingency by reporting the amount of money earned for responding and
      for not responding. Results suggest that TBI reduced the sensitivity of
      judgements and responding under select contingencies. These results lend some
      support to the view that TBI may reduce sensitivity to reinforcement
      contingencies. Furthermore, the investigation highlights the potential benefits
      of employing methods commonly used in human and animal operant research for the
      study of TBI.

PMID- 10887891
TI  - Multimodal early onset stimulation (MEOS) in rehabilitation after brain injury.
AB  - An early and consistent administration of the correct rehabilitation programme is
      of crucial importance for the restoration and improvement of cerebral function,
      as well as social reintegration. This has led to the development of a multimodal
      onset stimulation therapy (MEOS), which the neurosurgical intensive care unit
      administers during an early phase of rehabilitation to patients who have been in
      a coma for more than 48 hours after trauma. This study, which was carried out
      over a period of 2 years, focuses on 89 patients aged 16-65 years suffering from
      severe brain injury. Sixteen of these (age mean: 43.6 years) fulfil the criteria
      required to start the MEOS. The authors were able to identify significant changes
      in two of the patients' vegetative parameters (viz. heart and respiratory
      frequencies), even in cases of deep coma (GCS 3-4). The most significant changes
      were caused by tactile and acoustic stimulation. Standardized behavioural
      assessment turned out to be particularly advisable in cases of medium coma. Here,
      too, a stimulation of the tactile and acoustic senses resulted mainly in head and
      eye movements.

PMID- 10887892
TI  - Cardiac effects of contrast media in MR angiography: evaluation in an
      experimental model of myocardial ischemia.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the cardiac tolerability of
      paramagnetic contrast agents for magnetic resonance (MR) angiography in an in
      vitro model of ischemic rat heart. MATERIALS AND METHODS: The left anterior
      descending coronary artery was temporarily occluded in a perfused rat heart model
      to induce cardiac ischemia and reperfusion. A dose of 0.4 mL of gadobenate
      dimeglumine, of gadopentetate dimeglumine, or of D-mannitol was injected directly
      into the aorta both during the ischemia and during the reperfusion period. The
      left ventricular pressure and heart rate were recorded. RESULTS: Myocardial
      ischemia resulted in decreased cardiac activity, with a reduction in left
      ventricular pressure and heart rate. A further decrease in cardiac activity was
      temporarily induced by injection of contrast medium during both the ischemic and
      early reperfusion phases. Less marked responses were induced by a hyperosmolal
      solution of mannitol. CONCLUSION: These results suggest that the transient
      cardiac effects induced by bolus injection of paramagnetic contrast medium may be
      regarded as the combined effects of the osmotoxicity of the contrast medium
      solution and the chemotoxicity of the contrast medium molecule.

PMID- 10887893
TI  - Empiric assessment of parameters that affect the design of multireader receiver
      operating characteristic studies.
AB  - RATIONALE AND OBJECTIVES: The authors attempted to assess experimentally the
      magnitude of reader variability and the correlations and interactions among
      cases, readers, and modalities during observer performance studies and their
      possible effects on study design and sample size. MATERIALS AND METHODS:
      Published data from 32 selected receiver operating characteristic (ROC) studies
      were reviewed to compare the magnitude of the variance component from readers
      with the variance component from modality. Estimates of correlation and
      interactions among cases, readers, and modalities were also computed directly
      from ROC data ascertained during two large studies performed in our laboratory.
      Each of these two studies included 529 cases and six readers, but one study used
      eight modalities and the other nine. RESULTS: Published results indicate that
      reader variability is task dependent and larger (P < .05) than modality
      variability in detection of interstitial disease. Measured correlations between
      modalities for the same reader were task dependent and ranged from 0.35 to 0.59.
      Modality-by-reader and modality-by-case interactions often are not important
      factors. The random error term was greater than the modality-by-reader
      interaction in 11 of 20 comparisons and greater than the modality-by-case
      interaction in eight of 20 comparisons. CONCLUSION: Use of the same cases
      interpreted with different modes is justifiable in many situations because of the
      high variability from readers. This comprehensive review of existing ROC studies
      resulted in parameter assessments that can be used to better estimate sample-size
      requirements in multireader ROC studies.

PMID- 10887894
TI  - Transcatheter aspiration: the key to successful percutaneous treatment of deep
      venous thrombosis?
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to examine transcatheter
      aspiration as an adjunct to local thrombolysis in a porcine model of acute deep
      venous thrombosis (DVT). MATERIALS AND METHODS: DVT was induced in both hind
      limbs of five pigs. Thirty minutes later, bilateral thrombolysis was performed by
      using infusion guidewires placed coaxially through occlusion balloon catheters. A
      temporary venous filter was then placed in the inferior vena cava. The balloon
      catheters and infusion wire were removed, a 14-F sheath was placed on the right
      side, and aspiration of residual thrombi was attempted with 8- and 6-F catheters.
      At autopsy, the mass of any thrombus in the iliofemoral veins was measured, and
      residual thrombosis in the venous tributaries was graded at four sites.
      Thromboemboli in the inferior vena cava and the pulmonary circulation were also
      collected and weighed. RESULTS: With aspiration and lysis, the iliofemoral veins
      were cleared of thrombus in three of five limbs; from the remaining two, only
      0.09 and 0.15 g of thrombus were harvested. Except for the deep femoral vein in
      two legs, tributaries were free of thrombus. After thrombolysis alone, thrombi
      ranged in mass from 0.54 to 1.14 g (median, 0.70 g). Some thrombi were observed
      in most tributaries. One or two small emboli were found trapped by the caval
      filter and in the pulmonary circulation in four and three pigs, respectively.
      CONCLUSION: The primary axial veins and their tributaries can be rapidly cleared
      of thrombus by using thrombolysis with transcatheter aspiration, but this
      procedure is associated with the risk of pulmonary embolism.

PMID- 10887895
TI  - Pulmonary CT image classification with evolutionary programming.
AB  - RATIONALE AND OBJECTIVES: It is often difficult to classify information in
      medical images from derived features. The purpose of this research was to
      investigate the use of evolutionary programming as a tool for selecting important
      features and generating algorithms to classify computed tomographic (CT) images
      of the lung. MATERIALS AND METHODS: Training and test sets consisting of 11
      features derived from multiple lung CT images were generated, along with an
      indicator of the target area from which features originated. The images included
      five parameters based on histogram analysis, 11 parameters based on run length
      and co-occurrence matrix measures, and the fractal dimension. Two classification
      experiments were performed. In the first, the classification task was to
      distinguish between the subtle but known differences between anterior and
      posterior portions of transverse lung CT sections. The second classification task
      was to distinguish normal lung CT images from emphysematous images. The
      performance of the evolutionary programming approach was compared with that of
      three statistical classifiers that used the same training and test sets. RESULTS:
      Evolutionary programming produced solutions that compared favorably with those of
      the statistical classifiers. In separating the anterior from the posterior lung
      sections, the evolutionary programming results were better than two of the three
      statistical approaches. The evolutionary programming approach correctly
      identified all the normal and abnormal lung images and accomplished this by using
      less features than the best statistical method. CONCLUSION: The results of this
      study demonstrate the utility of evolutionary programming as a tool for
      developing classification algorithms.

PMID- 10887896
TI  - Quantitative analysis of breast parenchymal density: correlation with women's
      age.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the relationship between a
      woman's breast parenchymal density and her age by means of a quantitative method
      for measuring density from digitized mammograms. MATERIALS AND METHODS: The
      percentage of the breast considered to be dense was evaluated from mammograms of
      50 women stratified by age. Quantitative analysis based on the computer
      segmentation of tissue in digitized mammograms was performed by three expert
      mammographers. The results of this analysis were compared with results from a
      review of the film mammograms by three expert mammographers. RESULTS: A slight
      decrease in the percentage of breast considered to be dense with increased age
      was observed. The average difference in the percentage of dense breast tissue
      between the youngest and the oldest age groups was 6.4% based on the digital
      review and 14.6% based on the film review. Within each age group, the total
      variability was on the order of 75%. CONCLUSION: The difference in mean magnitude
      between the youngest and oldest age groups was small and may not be clinically
      important. The variability within an age group was large, which suggests that age
      is not a reliable indicator of percentage of dense breast tissue.

PMID- 10887897
TI  - Effectiveness of resident-prepared conferences in teaching imaging utilization
      guidelines to radiology residents.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the effectiveness of a resident
      prepared conference series for teaching imaging utilization guidelines to
      radiology residents. MATERIALS AND METHODS: Brown University radiology residents
      (n = 17) gave 61 presentations on imaging utilization to their colleagues during
      16 1-hour conferences. The residents were later examined on the topics presented
      and surveyed about their familiarity with the American College of Radiology
      appropriateness criteria, their exposure to issues of cost-effectiveness, and
      their degree of confidence in providing imaging consultation. The same
      examination and survey were administered to control residents from the University
      of Wisconsin (n = 14) and the Oregon Health Sciences University (n = 14). Scores
      were compared by using linear regression and Wilcoxon rank sum tests. RESULTS:
      Controlling for years in radiology residency, residents at Brown scored on
      average 16.0% (standard error = 2.2%) higher than residents at the other
      universities (P < .001). Controlling for institution, 3rd- and 4th-year residents
      scored on average 7.4% (standard error = 2.1%) higher than 1st- and 2nd-year
      residents (P = .001). Brown residents expressed more familiarity with American
      College of Radiology appropriateness criteria and appeared to have more exposure
      to cost-effectiveness issues in conferences than residents at Wisconsin or Oregon
      Health Sciences University (P < .005). Residents from the three universities did
      not differ in their level of confidence in providing imaging consultation.
      CONCLUSION: Resident-prepared conferences are an effective means of teaching
      imaging utilization guidelines to residents, but they do not affect the
      residents' perception of their ability to provide imaging consultation.

PMID- 10887898
TI  - Self-disturbance as a source of spatiotemporal heterogeneity: the case of the
      tallgrass prairie.
AB  - Tallgrass prairies are characterized by high levels of litter production, which
      has a profound effect on live biomass. Litter introduces a delayed inhibition of
      biomass growth, generating nonlinear dynamics and chaos. In this paper, we study
      a model of biomass-litter interaction, and focus on the litter persistence rate.
      The observed dynamics depends largely on this rate of year-to-year persistence.
      Different scenarios are explored and discussed. A spatially extended counterpart
      of such a model is later on introduced to account for the effects of space.
      Temporal chaos introduces spatial heterogeneity in terms of gaps where the
      current year biomass is almost zero. Such gaps can be colonized by fugitive
      species. The inhibitory effect of litter on biomass is thus an important source
      of intrinsic, small-scale heterogeneities that may promote diversity. On the
      other hand, the huge amounts of litter produced by the competitive dominants in
      tallgrass prairies enhance the probability of fires. Fires benefit, rather than
      depress, the superior competitive species. This fact explains why the
      intermediate disturbance hypothesis (IDH) stating that the highest diversity
      levels should be observed at intermediate disturbance frequencies, does not work
      in these communities. We define self-disturbances as small-scale disturbances
      affecting the growth and survival of the individuals that have generated them
      (e.g. due to the effects of the litter mass they produce). In the absence of
      other disturbances, self-disturbances can induce high heterogeneity and diversity
      levels in tallgrass prairies. We discuss the general implications of self
      generated disturbances for landscape heterogeneity and diversity of communities
      in which the main external perturbations benefit the dominant species.

PMID- 10887899
TI  - Simulation of regulated exocytosis of amylase from salivary parotid acinar cells
      by a consecutive reaction model comprising two sequential first-order reactions.
AB  - Amylase secretion from parotid acinar cells results from stimulus-regulated
      fusion of apical membrane and secretory granules that contain amylase. The time
      course of amylase secretion induced by various secretagogues has been reported.
      Calcium-mobilizing agonists such as carbamylcholine and substance P induce rapid
      and transient secretion while cAMP-mobilizing agonists such as isoproterenol
      cause long-term secretion. Combination of these two types of agonists results in
      a rapid and high rate of secretion. To explain the various time courses of these
      stimulations, it was assumed that amylase secretion is a consecutive reaction
      that consists of two first-order reactions. It was postulated that secretory
      granules were classified into three states: (A) pre-docked, (B) docked, and (C)
      fusion. The simple simulation could explain the time course of amylase secretion
      induced by various secretagogues by simply changing the rate constants for
      docking (reaction A to B) and fusion (reaction B to C) steps. It was also found
      that calcium mainly enhances the last fusion step and that cAMP activates the
      docking step. The amount of docked granules is estimated to be quite small, which
      accounts for why amylase secretion is regulated mainly by cAMP. The effects of
      the two types of secretagogues were synergistic, meaning that their intracellular
      signaling pathways are independent. At the same time, this also suggests that
      basal and enhanced secretion induced by two types of agonists have the same
      exocytotic process and that two stimuli independently activate the same machinery
      that mediates docking or fusion. This simulation is useful in analysis of the
      effects of secretion modulators and the molecular mechanism of amylase secretion.

PMID- 10887900
TI  - The basic reproductive ratio of a word, the maximum size of a lexicon.
AB  - Language is about words and rules. While there is some discussion to what extent
      rules are learned or innate, it is clear that words have to be learned. Here I
      construct a mathematical framework for the population dynamics of language
      evolution with particular emphasis on how words are propagated over generations.
      I define the basic reproductive ratio of word, R, and show that R > 1 is required
      for words to be maintained in the lexicon of a language. Assuming that the
      frequency distribution of words follow Zipf's law, an upper limit is obtained for
      the number of words in a language that relies exclusively on oral transmission.

PMID- 10887901
TI  - Evolutionarily stable strategy in a sex- and frequency-dependent selection model.
AB  - In this paper, a sex-dependent matrix game haploid model is investigated. For
      this model, since the phenotypes of female and male individuals are determined by
      alleles located at a single locus and are sex dependent, any given genotype
      corresponds to a strategy pair. Thus, a strategy pair is an ESS if and only if
      the allele corresponding to this strategy pair cannot be invaded by any mutant
      allele. We show that an ESS equilibrium must be locally asymptotically stable if
      it exists.

PMID- 10887902
TI  - Arithmetic or geometric normality of biological variation: an empirical test of
      theory.
AB  - Variation of biological populations is required for evolution by natural
      selection, and variance is a fundamental component in quantitative
      characterization of evolutionary differences and rates of change. Biological
      variation is widely understood to be normally distributed because of a general
      theoretical law of error. The law of error has two forms, and resulting normality
      may be arithmetic-where equivalent positive and negative deviations from
      expectation differ by equal amounts, or normality may be geometric-where
      equivalent deviations differ by equal proportions. Which law of error applies in
      biology can only be determined empirically, and this is surprisingly difficult. A
      new likelihood approach is developed here using data from anthropometric surveys
      of humans in two states in India: Maharashtra and Uttar Pradesh. Each state
      sample is large, but more importantly, each includes a large number of smaller
      subsamples. Likelihood support is additive, and subsamples are advantageous
      because (1) they are more homogeneous, (2) they yield probabilities and support
      scores in every case, and (3) significance can be evaluated first by tracing
      signs of the subsample support scores and then by comparing subsample support
      sums. Sign traces that fluctuate randomly show arithmetic and geometric normality
      to be indistinguishable. Two of 14 measurement variables studied here have
      subsample support sign traces differing from random, and one is significant in
      having a subsample support sum falling outside a 95% prediction interval for the
      12 fluctuating traces: geometric normality is favored by a factor of ca. 10(60).
      Six of 14 index variables have support sign traces differing from random, and all
      are significant in having subsample support sums falling outside a 95 %
      prediction interval for the 8 fluctuating traces: geometric normality is favored
      by factors of 10(8) or more. Arithmetic and geometric normality cannot be
      distinguished for 21 of 28 variables studied here, but whenever alternatives are
      distinguishable geometric normality is consistently and strongly favored. This
      means that the applicable law of errors is proportional. In practical terms,
      arithmetic measurements must be transformed using logarithms to represent both
      the geometric normality of biological variation and the relative functional
      significance of measurements appropriately.

PMID- 10887903
TI  - Gaseous templates in ant nests.
AB  - We apply a diffusion model to the atmosphere of ant nests. With particular
      reference to carbon dioxide (CO2), we explore analytically and numerically the
      spatial and temporal patterns of brood- or worker-produced gases in nests. The
      maximum concentration within a typical one-chamber ant nest with approximately
      200 ants can reach 12.5 times atmospheric concentration, reaching 95% of
      equilibrium concentrations within 15 min. Maximum concentration increases with
      increasing number of ants in the nest (or production rate of the gas), distance
      between the centre of the nest ants and the nest entrance, entrance length, wall
      thickness, and with decreasing entrance width, wall permeability and diffusion
      coefficient. The nest can be divided into three qualitatively distinct regions
      according to the shape of the gradient: a plateau of high concentration in the
      back half of the nest; an intermediate region of increasingly steep gradient
      towards the entrance; and a steep linear gradient in the entrance tunnel. These
      regions are robust to changes in gas concentrations, but vary with changes in
      nest architecture. The pattern of diffusing gases contains information about
      position and orientation relative to gas sources and sinks, and about colony
      state, including colony size, activity state and aspects of nest architecture. We
      discuss how this diffusion pattern may act as a "dynamic template", providing
      local cues which trigger behavioural acts appropriate to colony needs, which in
      turn may feed back to changes in the gas template. In particular, wall building
      occurs along lines of similar concentration for a variety of nest geometries;
      there is surprising convergence between the period of cycles of synchronously
      active ants and the time taken for CO2 levels to equilibrate; and the
      qualitatively distinct regions of the "dynamic template" correspond to regions
      occupied by different groups of ants.

PMID- 10887904
TI  - The kinetic basis of a general method for the investigation of active site
      content of enzymes and catalytic antibodies: first-order behaviour under single
      turnover and cycling conditions.
AB  - The theoretical foundation has been laid for the investigation of catalytic
      systems using first-order kinetics and for a general kinetic method of
      investigation of the active site content, E(a), of enzymes, catalytic antibodies,
      and other enzyme-like catalysts. The method involves a combination of steady
      state and single-turnover kinetics to provide Vmax and Km and k(lim)(obs) and
      K(app)(m), respectively. The validity of the method is shown to remain valid for
      two extensions of the simple two-step enzyme catalysis model (a) when the
      catalyst preparation contains molecules (Eb) that bind substrate but fail to
      catalyse product formation and (b) when the catalyst itself binds substrate non
      productively as well as productively. The former is a particularly serious
      complication for polyclonal catalytic antibodies and the latter a potential
      complication for all catalysts. For the simple model and for (b) Vmax/k(lim)(obs)
      provides the value of [Ea]T and for (a) its upper limit. This can be refined by
      consideration of the relative values of Km and the equilibrium dissociation
      constant of EbS. For the polyclonal catalytic antibody preparation investigated,
      the fact that K(app/m) > Km demonstrates for the first time the presence of a
      substrate-binding but non-catalytic component in a polyclonal preparation. First
      order behaviour in catalytic systems occurs not only with a large excess of
      catalyst over substrate but also with lower catalyst/substrate ratios, including
      the equimolar condition, when K(app)(m) >> [S]0, a phenomenon that is not widely
      appreciated.

PMID- 10887905
TI  - Mathematical modelling of nitric oxide activity in wound healing can explain
      keloid and hypertrophic scarring.
AB  - Keloid and hypertrophic lesions are both types of scarring pathologies which
      arise as a consequence of excess collagen deposition during the wound healing
      process. The exact mechanism by which this occurs is not understood and currently
      no effective treatment exists. In this paper, we study the possible role of
      nitric oxide in excess scar formation. In recent years, the physiological role of
      this free radical in mammalian tissue has been extensively studied; in particular
      numerous groups have studied its role in wound healing. We describe a
      mathematical model which offers a possible explanation for keloid scarring in
      terms of the presence of higher than normal nitric oxide concentrations related
      to the fact that nitric oxide stimulates synthesis of collagen by fibroblasts. As
      a consequence of this, we put forward a suggestion for a treatment strategy
      involving the surgical excision of the keloid lesion combined with the
      application of a low-dose nitric oxide inhibitor. In addition, we show that a
      quasi-steady-state analysis of our model reveals a possible approach to
      distinguishing between hypertrophic and keloid lesions, a task which has to date
      proven to be clinically difficult. We also present an extended model which
      confirms these results in the context of a more complicated and biologically more
      realistic system. The fuller model demonstrates additional features of keloid and
      hypertrophic scarring which we were not able to consider in the basic model, and
      as a consequence further supports our hypothesis that nitric oxide activity could
      play a key role in keloid scarring.

PMID- 10887906
TI  - Resource competition in stage-structured populations.
AB  - Two models are made to account for the dynamics of a consumer-resource system in
      which the consumers are divided into juveniles and adults. The resource grows
      logistically and a type II functional response is assumed for consumers. Resource
      levels determine fecundity and maturation rates in one model, and mortality rates
      in the other. The analysis of the models shows that the condition for
      establishment of consumers is that the product of per capita fecundity rate and
      maturation rates is higher than the product of juvenile and adult per capita
      decay rates at a resource level equal to its carrying capacity. This result
      imposes a minimal abundance of resource able to maintain the consumers. A second
      result shows an equilibrium stage structure, with a small instability when
      juveniles and adults mean saturation constants are different. The implications of
      these results for community dynamics are discussed.

PMID- 10887907
TI  - Environmental temperature and human growth in early life.
AB  - A link between adult human body size and environmental temperature, evolved
      through adaptation to heat stress, was first recognized a century ago and is now
      well accepted in human biology. Increasing heat stress favours smaller body size
      and an increased ratio of surface area to mass. However, possible effects of
      temperature on growth in early life have not been considered. Many developing
      country populations inhabit relatively hot environments compared to
      industrialized populations, but growth faltering in developing countries is
      invariably attributed to the combination of poor nutrition and infection. The aim
      of this study was to model the theoretical effect of growth faltering on cooling
      capacity in early life. Data on weight, length and total energy expenditure were
      selected from the literature. Three types of growth (normal growth, stunting and
      wasting) were considered, and the relationship between body size and heat
      production investigated. Relative to normal growth, stunting causes little
      increase in the area-to-mass ratio until 2 years of age, and results in little
      increase in cooling capacity during infancy. Wasting increases the area-to-mass
      ratio by > 15% in early infancy, and by 10% thereafter, equivalent to a similar
      increase in cooling capacity. These findings demonstrate theoretically that
      growth faltering can relieve heat stress in both infancy and childhood. The
      hypothesis that heat stress plays a role in human growth faltering in hot
      environments therefore merits empirical investigation.

PMID- 10887908
TI  - Inheritance in the conditional strategy revisited.

PMID- 10887909
TI  - Need for occlusal therapy and prosthodontic treatment in the management of
      temporomandibular disorders. Part I. Occlusal interferences and occlusal
      adjustment.
AB  - This review, divided into two parts, evaluates the literature on the relationship
      between dental occlusion and temporomandibular disorders (TMD) and the need for
      occlusal therapy in the management of TMD. The first part of the review focuses
      on the aetiological importance of occlusal interferences and the place of
      occlusal adjustment in the management and prevention of signs and symptoms of
      TMD. This has long been a controversial issue, which has not yet been resolved.
      The literature does not give strong support for the role of occlusion in the
      aetiology of TMD. Experienced clinicians also repudiate the need for occlusal
      adjustment in the management of TMD, whereas (less experienced) general dentists
      adhere to a concept focusing on the occlusion in diagnosis and treatment of TMD.
      There is a consensus that generalized prophylactic occlusal adjustment is not
      justified. There is an obvious need for research with evidence-based methods, to
      be able to answer the many remaining questions in this field.

PMID- 10887910
TI  - Impression pressures against teeth in a partially edentulous model with a mobile
      tooth: influence of impression tray design.
AB  - The purpose of the present study was to examine the effect of custom tray designs
      on local pressures against teeth during the impression procedure. In a previous
      study, a partially edentulous simulation model with a mobile tooth was used, and
      the effect of custom tray designs on the displacement of the mobile tooth was
      examined during the impression procedure. Based on that study's results, we have
      assumed that the differences in impression pressures between the labial and the
      lingual sides of a mobile tooth could either cause or affect displacement. The
      present study was undertaken to determine the local impression pressures against
      each side of three anterior teeth, including one mobile tooth, using the same
      simulation model and the same custom trays as in the previous study. It was found
      that the local pressures exerted against teeth during the impression procedure
      were affected by the custom tray designs and varied according to the coronal
      shape, axis inclination and location of the teeth.

PMID- 10887911
TI  - Photoelastic stress analysis in perforated (Rochette) resin bonded bridge design.
AB  - Rochette described the perforated cast metal bonded design for splinting
      periodontally compromised teeth. The design was later used for replacing missing
      teeth. The main causes of failure of the perforated (Rochette) type design were
      attributed to inappropriate case selection and erosion of the composite from
      perforations. The aim of this study was to analyse the effect of stress magnitude
      and direction on failure of perforated resin bonded bridges (RBBs). The objective
      was to compare stress magnitudes in this design with those reported on the non
      perforated RBBs. Photoelastic modelling materials were selected to represent the
      relative stiffnesses of a posterior mandibular and an anterior maxillary
      perforated (Rochette) type design. The sizes of the models were scaled to x 2.5
      in order to enhance visual analysis of the stress patterns. Stress magnitudes
      were quantified from isochromatic fringes and stress directions were evaluated
      from stress trajectories. These revealed a high-stress concentration around the
      perforations, particularly for those at the proximo-lingual/palatal (connector)
      areas. This experimental study revealed that the main reason for failure of
      Rochette designs is deformation at the perforations.

PMID- 10887912
TI  - EMG-force relationships are influenced by experimental jaw-muscle pain.
AB  - The bite force at different levels and the corresponding electromyographic (EMG)
      activity of the masseter and anterior temporalis muscles were recorded in 12
      healthy subjects in order to evaluate the modulation of EMG-force curves by a
      standardized painful stimulus. Hypertonic saline (5%) was infused into the right
      masseter muscle for up to 15 min to induce pain. The pain intensity was scored
      continuously by the subjects on a 10-cm visual analogue scale (VAS). Subjects
      were asked to bite on a force transducer at the maximum voluntary bite force
      (MVBF). They were then asked to bite at submaximum levels of 12, 25, 37, 50, 67,
      75 and 87% of MVBF. The biting was performed in three different positions (right
      first molar, left first molar and incisor) before, during and after infusion.
      Hypertonic saline caused moderate pain during infusion (mean VAS +/- s.e.m. =
      6.5+/-0.5 cm). Both the MVBF and the maximum EMG activity in the right masseter
      and the left anterior temporalis muscles were significantly decreased during
      muscle pain when the subjects bit on the painful side. The EMG-force curves could
      be fit by linear relationships. The slope of the curve became less steep in the
      right masseter muscle during and after painful biting in every position. The
      results suggest that tonic saline-induced jaw-muscle pain is able to modulate the
      motor unit recruitment pattern of the jaw-closing muscles on the painful side.
      The main effect of pain in this experiment was an inhibition of static EMG
      activity.

PMID- 10887913
TI  - The bond of two adhesive resins to alumina blasted and heat-treated gold alloy
      surfaces.
AB  - The purpose of this study was to test in shear mode the bond strengths of two BIS
      GMA resin cements bonded to alumina blasted and heat-treated gold alloy surfaces.
      This was carried out in order to investigate the manufacturer's claim of the
      superiority of Panavia 21 over Panavia Ex. Alumina blasted gold alloy surfaces
      were cemented in pairs with either Panavia Ex or Panavia 21 resin cements. Heat
      treated gold alloy surfaces were similarly paired. The luted pairs were stored in
      water at 37 degrees C for 48 h before bond was tested with shearing forces.
      Although the differences were not statistically significant, it was found that
      Panavia 21 formed stronger bonds on the alumina blasted surfaces than Panavia Ex.
      However, Panavia Ex exhibited higher mean strength values than Panavia 21 on the
      heat-treated surfaces. Not only was this difference statistically significant,
      but the bond strength values obtained for Panavia Ex on this surface were the
      highest in the data set. On the basis of bond testing in shear, it would appear
      that Panavia 21 is inferior to Panavia Ex on heat-treated gold alloy surfaces.

PMID- 10887914
TI  - Effects of timing and heat treatment of silanated porcelain on the bond strength.
AB  - This study examined the effects of postsilanization interval and heat treatment
      on shear bond strength of composite resin to porcelain. One hundred and eighty
      square-shaped specimens were fabricated and sanded flat sequentially. The
      specimens were then randomly placed into six groups and 18 subgroups of 10
      specimens each. An experimental and three commercially available silane systems,
      including two one-mix and one two-mix systems, were tested in this study. No
      silane treatment specimen was used as control. Specimens from the experimental
      and one of the Mirage groups were selected for heat treatment for 60 min at 60
      degrees C. Three post-silanization intervals were scheduled. After incubation, a
      dual cure composite resin (Mirage FLC) was placed on the silanated surfaces and
      light-cured. All specimens were stored in 37 degrees C, 2% saline solution for 1
      week and subjected to shear test using an Instron machine with cross-head speed
      of 5 mm/min. ANOVA and Scheffe tests were used to analyse data with confidence
      level at 95%. The mean values of the shear bond strengths ranged from 2.8 to 23.3
      MPa. All groups showed significantly higher bond strength than the control group
      at the 3 min, 24 h and 1 week post-silanization periods (P < 0.05). Heat
      treatment groups recorded an increase in the shear bond strength and maintained
      significantly higher bond strength values (P < 0.05). In conclusion, bond
      strength of composite resin to porcelain resulting from silanization of porcelain
      increased after heat treatment and during the post-silanization periods. The bond
      strength also varied for different silane coupling agents tested in this study
      especially in the one-mix system.

PMID- 10887915
TI  - The relationship between frontal facial morphology and occlusal force in
      orthodontic patients with temporomandibular disorder.
AB  - The aim of this study was to investigate the relation between frontal
      craniofacial morphology and the distribution of occlusal force in orthodontic
      patients with and without TMD. Experimental data were obtained from 45 female
      orthodontic patients (TMD-free group: 22 subjects; TMD group: 23 subjects) using
      the pressure-sensitive sheet. The following results were obtained: (1) There were
      significant differences in the gonial angle width and the mandibular deviation of
      the postero-anterior cephalogram between the two groups. (2) There were
      significant differences in occlusal force, occlusal contact area and average
      occlusal pressure between the two groups. (3) On the relation between the frontal
      craniofacial morphology and the occlusal data, the asymmetry indices of occlusal
      force and occlusal contact area showed significant positive correlations to the
      mandibular deviation and the ratios of maxillary and gonial angle widths in the
      TMD group. The TMD-free group showed the smaller mandibular deviation and the
      smaller asymmetry indices of occlusal force and occlusal contact area than those
      in the TMD group. It could be concluded that orthodontic patients with TMD may
      have not only the morphological disharmony but also the imbalance of occlusal
      force.

PMID- 10887916
TI  - Effects of aging on repair of resin-modified glass-ionomer cements.
AB  - The effects of aging on the repair bond strengths of resin-modified glass-ionomer
      cements after different methods of surface conditioning were studied. Surface
      conditioning methods included the following: maleic acid; maleic acid with resin
      application; polyacrylic acid; polyacrylic acid with resin application. Shear
      bond testing between the aged and new material was carried out with an Instron
      Universal testing machine. Surface conditioning with maleic acid and resin
      application gave the highest repair bond strengths at 3 and 6 months. There was,
      however, no statistically significant difference in bond strengths between the
      different treatment groups after both 3 and 6 months storage. Intergroup
      comparisons revealed no significant difference in failure modes after both
      storage periods. For all treatment groups, no significant difference in repair
      bond strengths was noted between storage after 1 week, 3 and 6 months. There
      appears to be a general decrease in repair bond strengths for all treatment
      groups after 3 months storage. The clinical repair of resin-modified glass
      ionomer cements after this period of time is therefore not recommended.

PMID- 10887917
TI  - Penetration of the pulp chamber by carbamide peroxide bleaching agents on teeth
      restored with a composite resin.
AB  - This in vitro study was performed to evaluate the effect of various
      concentrations of carbamide peroxide bleaching agents on the pulp chambers of
      teeth restored by a composite resin. Forty-nine human extracted anterior teeth
      were used. All the teeth were sectioned 3 mm apical of the cemento-enamel
      junction and the intracoronal tissue removed. The teeth were separated into the
      seven groups each containing seven teeth. Twenty-eight teeth were used as
      controls (groups I-IV), standardized cavities were prepared with the remaining 21
      teeth (groups V, VI, VII), and restored with a hybrid composite resin (XR
      Herculite). Acetate buffer was placed in the pulp chamber to absorb and stabilize
      any peroxide that might penetrate. Group I was exposed only to distilled water.
      Groups II and V were applied with 10% CP (Contrast PM), groups III and VI were
      applied with 15% CP (Contrast PM), groups IV and VII were applied with 35% CP
      (Quik Start) and left for 30 min at 37 degrees C. Then, the acetate buffer
      solution in the pulp chamber of each tooth was removed and the chamber was then
      rinsed twice with 100 ml of distilled water. The contents then had leucocryctal
      violet and enzyme horseradish peroxidase added. The optical density of the
      resulting blue solution was determined spectrophotometrically, and was converted
      into microgram equivalents of hydrogen peroxide. A higher level of bleaching
      agent penetrated into the pulp chamber in the restored teeth than in the sound
      teeth.

PMID- 10887918
TI  - A pooled-data analysis of three randomized, double-masked, six-month clinical
      studies comparing the intraocular pressure reducing effect of latanoprost and
      timolol.
AB  - PURPOSE: To compare the intraocular pressure (IOP) reduction by latanoprost and
      timolol, and to study factors of prognostic value for assessing this reduction.
      METHODS: We analyzed 829 patients included in three phase 111 studies comparing
      six months' treatment with 0.005% latanoprost once daily and 0.5% timolol twice
      daily in patients with open-angle glaucoma or ocular hypertension. Analysis of
      covariance controlled for differences in baseline IOP and sex was used to assess
      the IOP reduction. RESULTS: Latanoprost reduced diurnal IOP (average of morning,
      noon and afternoon assessments) by 7.7 mmHg (31%) and timolol by 6.5 mmHg (26%)
      after six months of treatment. Thus the diurnal IOP was reduced 1.2 mmHg (18%)
      more with latanoprost than with timolol (p<0.001). Latanoprost-treated patients
      showed a further decrease in morning IOP of 0.7 mmHg (9%, p<0.001) from the
      initial morning IOP reduction obtained at two weeks. No such further decrease in
      IOP was seen with timolol. Higher baseline diurnal IOP resulted in a larger
      diurnal reduction during treatment with both drugs (p<0.001). Diurnal IOP in
      women was reduced 0.7 mmHg (11%) less than males with both drugs (p<0.001).
      CONCLUSIONS: Latanoprost was more effective than timolol in reducing mean diurnal
      IOP. The effect after two weeks was maintained for timolol while with latanoprost
      there was a further, significant IOP reduction from two weeks to six months.
      Baseline IOP was the only factor of clinical importance found to be of prognostic
      value for assessing the IOP reduction.

PMID- 10887919
TI  - The effect of propofol and alfentanil on the increase in intraocular pressure due
      to succinylcholine and intubation.
AB  - PURPOSE: The aim of this study was to evaluate the effects of propofol and
      alfentanil on the increase in intraocular pressure (IOP) due to succinylcholine
      and intubation, in comparison with thiopental sodium and vecuronium bromide.
      METHODS: Forty patients aged 20-50 years, scheduled for elective surgery
      requiring endotracheal intubation, were assigned to four groups of ten. General
      anesthesia was induced with 2.5 mg/kg propofol in Group I, 2.5 mg/kg propofol and
      10 microg/kg alfentanil in Group II and 5 mg/kg thiopental in Groups III and IV;
      muscle relaxation was obtained with either 1.5 mg/kg succinylcholine (Group I, II
      and III) or 0.1 mg/kg vecuronium bromide (Group IV). In all patients mean
      arterial pressure, heart rate, oxygen saturation and IOP were recorded before
      (baseline) and after induction, after the muscle relaxant and after endotracheal
      intubation. RESULTS: Compared with their baseline values in Group I IOP decreased
      significantly after propofol (p<0.01) and increased significantly after
      intubation (p<0.01). In Group II IOP decreased significantly after propofol and
      alfentanyl (p<0.001), remained low after succinylcholine (p<0.01) and did not
      change after intubation. In Group III IOP decreased significantly after
      thiopental (p<0.001) and increased significantly after intubation (p<0.001). In
      Group IV it decreased significantly after thiopental (p<0.001), remained low
      after vecuronium (p<0.001) and increased significantly after intubation (p<0.05).
      CONCLUSIONS: In all Groups, IOP did not increase significantly after
      succinylcholine, but only anesthesia induced with propofol and alfentanil
      prevented the increase in IOP due to intubation.

PMID- 10887920
TI  - Effect of cytokines on regulation of the production of transforming growth factor
      beta-1 in cultured human Tenon's capsule fibroblasts.
AB  - PURPOSE: Transforming growth factor-beta1 (TGF-beta1) is thought to play a
      pivotal role in the regulation of the wound healing process after glaucoma
      filtering surgery. The aim of the present study was to investigate whether
      platelet-derived growth factor isoforms (PDGF-AA, PDGF-BB), basic fibroblast
      growth factor (bFGF), epidermal growth factor (EGF), interleukin-1beta (IL-1beta)
      and transforming growth factor-beta1 (TGF-beta1) modulate the production of
      latent and/or active TGF-beta1 by cultured human Tenon's capsule fibroblasts
      (HTF). METHODS: Human Tenon's capsule fibroblasts were seeded at two different
      densities (30 cells/mm2 and 150 cells/mm2) and stimulated for five days with PDGF
      AA, PDGF-BB, bFGF, EGF, IL-1beta and TGF-beta1. Control cells were treated with
      serum-free medium (WM/F12). The concentrations of latent and active TGF-beta1 in
      the medium were determined using an immunoassay before and after activation of
      TGF-beta1 by transient acidification. RESULTS: The concentration of latent TGF
      beta1 in conditioned media from HTF seeded at high density (150 cells/mm2)
      significantly increased after stimulation with 5 ng/ml TGF-beta1 (151.5 +/-41.7
      pg/ml) or 10 ng/ml IL-1beta (45.7+/-8.1 pg/ml). The concentration of active TGF
      beta1 in conditioned media also significantly increased after stimulation of HTF
      with 5 ng/ml TGF-beta1 (48.4+/-27.5 pg/ml). CONCLUSIONS: The present results
      indicate that TGF-beta1 is the most potent inducer of its own synthesis in HTF.
      Activation of an autocrine TGF-beta1 loop may play a role in the wound healing
      response after glaucoma filtering surgery.

PMID- 10887921
TI  - Short-wavelength automated perimetry and neuroretinal rim area.
AB  - PURPOSE: To determine the correlation between neuroretinal rim area and
      functional losses detected by short-wavelength automated perimetry (SWAP) in a
      population of patients with suspected glaucoma. METHODS: Forty-two eyes of 42
      ocular hypertensive subjects who met the selection criteria (intraocular pressure
      greater than 21 mm of Hg and normal conventional visual fields) were studied. A
      planimetric optic nerve head study was performed, determining the total and
      sectorized neuroretinal rim areas. SWAP was also done, with a modified Humphrey
      field analyzer. RESULTS: There were no significant correlations between the
      neuroretinal rim areas and the global perimetric parameters. However, the
      correlations between the inferotemporal neuroretinal rim area and some
      superonasal visual field regions (areas 3 and 4) were significant. CONCLUSIONS:
      There is a relation in the topography of some visual field areas assessed by SWAP
      and the inferotemporal neuroretinal rim area, which may play a role in the
      diagnosis and follow-up of suspected glaucoma.

PMID- 10887922
TI  - Evaluation of retinoic acid ophthalmic emulsion in dry eye.
AB  - PURPOSE: An oil in water emulsion of 0.01% all-trans-retinoic acid (tretinoin)
      was prepared and clinically evaluated in dry eye patients. METHODS: The
      ophthalmic emulsion consisted of 10% of arachis oil and 90% of the hydrogel of
      Carbopol 940. To evaluate retinoic acid emulsion clinically, a placebo
      controlled, open-labeled, randomized study was performed with 22 dry-eye
      patients. Symptoms were recorded before and after the treatments. The Schirmer I
      test, measurement of tear film break-up time (BUT), rose Bengal and fluorescein
      staining of cornea and conjunctiva, and mucus fern test were done. RESULTS:
      Retinoic acid did not improve the dryness, photophobia and foreign body sensation
      more than placebo. Schirmer test and BUT were significantly improved by retinoic
      acid treatment. Corneal and conjunctival epithelium maintained their
      characteristics during the use of retinoic acid, as indicated by rose Bengal and
      fluorescein staining. CONCLUSIONS: Ophthalmic emulsion of retinoic acid can be
      suggested as a promising approach for the treatment of dry eye.

PMID- 10887923
TI  - Dacryostenosis in newborns: probing, or syringing, or both?
AB  - PURPOSE: This prospective study was designed to establish whether it is more
      effective to treat symptomatic congenital nasolacrimal duct obstruction by
      probing, or high-pressure irrigation, or both. METHODS: During the period
      February 1991 to January 1999, 228 infants (300 nasolacrimal ducts) were examined
      (132 males, 96 females, age range 12-13 months). These patients were divided into
      three groups of 100 ducts each. The first group was probed only; in the second
      group the nasolacrimal ducts were irrigated under high pressure using methylene
      blue-stained saline, and the third group was probed and irrigated in the same
      setting. The procedures were done under light general anesthesia. RESULTS: Ninety
      one ducts in the first group improved after probing. In the second group 64 ducts
      improved after irrigation. In the third group 96 ducts improved after both
      probing and irrigation. CONCLUSIONS: To treat symptomatic congenital nasolacrimal
      duct obstruction, it is more effective to combine high-pressure irrigation and
      probing. This gives a better success rate, first in treatment and secondarily,
      permitting intraoperative verification of the patency of the excretory lacrimal
      system.

PMID- 10887924
TI  - Circulating antibodies to human and bovine cornea in human keratoplasty.
AB  - PURPOSE: To compare anti-human cornea and anti-bovine cornea serum reactivity in
      corneal transplantation and pathology. METHODS: We investigated the presence of
      IgG and IgM antibodies to bovine corneal extract (BCE) and human corneal extract
      (HCE) by ELISA in 48 healthy adults and in 30 corneal allograft recipients before
      and after grafting. Baseline levels of antibodies in healthy controls served to
      establish a positivity threshold. Anti-HLA antibodies were investigated in all
      patients. RESULTS: Preoperatively, five and one patient were positive
      respectively for IgG and IgM anti-BCE; one and ten patients were positive for IgG
      and IgM anti-HCE. The presence or absence of antibodies was not modified after
      grafting, and was not associated with rejection. Anti-HCE of the IgM class were
      more frequent in patients with keratoconus. Two patients had anti-HLA antibodies.
      CONCLUSIONS: Antibodies to non-HLA corneal antigens are detectable in corneal
      allograft recipients. Reactions against bovine and human substrates differ in
      frequency and class. This reactivity is not modified after grafting or rejection,
      but is increased in corneal disorders, including keratoconus.

PMID- 10887925
TI  - Retinal nerve fiber layer measurements using scanning laser polarimetry after
      photorefractive keratectomy.
AB  - PURPOSE: To assess the effects of corneal depth changes on retinal nerve fiber
      layer (RNFL) postoperative measurements in myopic patients who had undergone
      photorefractive keratectomy (PRK). METHODS: A total of 120 myopic patients
      underwent PRK for myopia (range -2 to -10 diopters) and were divided into three
      groups according to their myopic correction: lower than 3 diopters (low myopia
      group), between 3 and 6 diopters (medium myopia group), over 6 diopters (high
      myopia group). RNFL parameters were evaluated preoperatively and 5 days, 3 months
      and 6 months after surgery, using a GDx NFA II scanning laser ophthalmoscope.
      RESULTS: Significant changes were seen in the symmetry, superior maximum, and
      average thickness, comparing baseline with six-month measurements (p=0.008,
      0.027, 0.015 respectively). Dividing the sample according to attempted myopic
      correction, it was found that mean postoperative RNFL thickness was significantly
      lower after PRK only in the high myopia group. Mean RNFL thickness did not change
      with time (p=0.884). Ablation depth was correlated with a change in RNFL
      thickness by the sixth postoperative month for each group. These variables were
      significantly related only in the high myopia group (p=0.003). CONCLUSIONS: As
      polarised light penetrates the ablation area, morphological and functional
      changes might affect Gdx NFA II measurements. It must always be borne in mind
      that RNFL thickness can decrease either in cases of glaucoma or after PRK for
      high myopia, so close attention must be paid to interpreting these measurements
      in patients who have undergone PRK.

PMID- 10887926
TI  - The efficacy of 2.5% phenylephrine and flurbiprofen combined in inducing and
      maintaining pupillary dilatation during cataract surgery.
AB  - PURPOSE: To evaluate the effectiveness of phenylephrine 2.5% and flurbiprofen
      0.03% combined in inducing and maintaining mydriasis during extracapsular
      cataract extraction (ECCE). METHODS: One hundred patients undergoing ECCE +
      intraocular lens (IOL) implantation were randomly divided into four groups. The
      first group was given phenylphrine 10%, the second group phenylephrine 10% +
      flurbiprofen, the third group phenylephrine 2.5% and fourth group phenylephrine
      2.5% + flurbiprofen. Cyclopentolate 1% was used in all patients. Phenylephrine
      and cyclopentolate were instilled preoperatively four times during 1 hour and
      flurbiprofen was given four times the day before surgery and twice with an hour's
      interval before operation. Pre-operative and post-cortex aspiration horizontal
      pupil diameters were measured with callipers viewed through the operating
      microscope. RESULTS: Pupil diameters in pre-operative and post-cortex aspiration
      were no different in the 2.5% and 10% phenylephrine groups (p>0.05). Both
      diameters were larger and pupillary constriction was smaller in the flurbiprofen
      groups (p<0.05). CONCLUSIONS: 2.5% phenylephrine was as effective as 10%
      phenylephrine, with and without flurbiprofen, in inducing and maintaining pupil
      dilatation during ECCE surgery.

PMID- 10887927
TI  - Metachronous tumor development in unilateral retinoblastoma.
AB  - PURPOSE: A series of 205 retinoblastoma (RB) patients referred to the Department
      of Ophthalmology at the University of Siena (Italy) was evaluated in order to
      assess the proportion of unilateral cases later developing tumors in the
      companion eye ("metachronous" bilateral retinobastoma) (MBRB). METHODS: The total
      number of unilaterally affected patients developing tumors in the fellow eye was
      recorded and the risk factors assessed for the development of asynchronous
      bilateral retinoblastoma, i.e., family history, tumor multifocality and early age
      at diagnosis. RESULTS: Only two out of 133 (1.5%) unilateral retinoblastoma
      patients in our series could be considered affected by MBRB. CONCLUSIONS: The
      incidence of MBRB in our series was negligible (1.5% of all unilateral cases)
      compared to other reports. None of the reported risk factors for the development
      of tumors in the fellow eye was relevant in the present series. Although close
      follow-up of some unilateral cases is still recommended, thorough examination of
      the fellow eye, to search for lesions in the peripheral retina, is essential in
      all cases of unilateral RB. MBRB may be a distinctive clinical entity with
      specific clinical, genetic and prognostic features. However, all these aspects
      need to be better investigated in larger series.

PMID- 10887928
TI  - Factors influencing anatomic and visual results in primary scleral buckling.
AB  - PURPOSE: To identify the factors influencing anatomical and visual results in
      cases of rhegmatogenous retinal detachment undergoing primary scleral buckling.
      METHODS: A retrospective study of 233 eyes of 226 patients was done. The data
      were evaluated by univariate analysis and stepwise logistic regression analysis.
      RESULTS: Retinal reattachment was achieved with primary scleral buckling in 197
      eyes (84.5%). The extent of retinal detachment, preoperative proliferative
      vitreoretinopathy (PVR), preoperative visual acuity and relative afferent
      pupillary defects were identified as influencing anatomical results, by
      univariate analysis. The predictive roles of extent of retinal detachment
      (P<0.0001) and preoperative PVR (P=0.0085) were shown to be significant by step
      wise logistic regression. As well as the above factors, the patient's age, the
      duration of symptoms and the status of the macula were predictors of visual
      results, by univariate analysis. Stepwise logistic regression analysis confirmed
      the predictive roles of preoperative visual acuity (P<0.0001) and the extent of
      retinal detachment (P=0.0089). CONCLUSIONS: Cases with a larger extent of retinal
      detachment, more advanced preoperative PVR and poorer preoperative visual acuity
      have less favorable anatomical and functional results.

PMID- 10887929
TI  - Primary vitrectomy for rhegmatogenous retinal detachment: an analysis of failure.
AB  - PURPOSE: To find the cause of failure in primary vitrectomy for rhegmatogenous
      retinal detachment. METHODS: Retrospective review of 171 consecutive cases of RRD
      treated by primary pars plana vitrectomy (PPV) from a tertiary referral centre to
      identify the 25 cases in which surgery had failed. Detachments with giant or
      macula breaks at initial presentation, with proliferative diabetic retinopathy or
      with PVR greater than grade B were excluded. RESULTS: The failure rate after the
      first operation was 14.6% and the commonest cause of failure was missed retinal
      breaks, accounting for 64.3% of failures. CONCLUSION: Missed retinal breaks are
      the commonest cause of failure of primary PPV for RRD although proliferative
      vitreoretinopathy may contribute to surgical failure. This re-emphasises the
      importance of assiduous peroperative retinal examination.

PMID- 10887931
TI  - Merkel cell carcinoma of the eyelid: a case report.
AB  - A 22-year-old woman who presented with a tumour of the upper eyelid with
      clinical, histological, immunohistochemical and ultrastructural features of a
      Merkel cell carcinoma is reported. This is a unique case of Merkel cell carcinoma
      in such a young patient. This neuroendocrine tumour is typically found in the
      elderly. It can grow rapidly, has the potential for local recurrence and early
      metastatic spread. The authors recommend wide resection of the primary site,
      which proved effective in this case.

PMID- 10887930
TI  - Two nonsense mutations of PAX6 in two Japanese aniridia families: case report and
      review of the literature.
AB  - PURPOSE: To identify PAX6 mutations in patients from four Japanese families with
      aniridia. METHODS: Polymerase chain reaction (PCR)-single stand conformational
      polymorphism (SSCP) analysis (SSCA) was performed in probands of the families,
      and restriction analysis using MaeIII or AvaI was carried out in other affected
      family members. RESULTS: PCR-SSCA demonstrated in the proband from one family an
      extra-band in the PCR product for PAX6 exon 8. Base sequence analysis revealed
      that the patient is a heterozygote for a C to T transition mutation at codon 203.
      DNAs from the patient and another affected member in the same family were cut
      with MaeIII into two fragments, while non-affected members in the family showed
      only one MaeIII fragment, the result confirmed the mutation. In another family,
      PCR-SSCA revealed an extra-band in the PCR product for exon 9. Sequencing
      detected a C-->T substitution at codon 240 in the patient, the mutation resulted
      in loss of an AvaI site. AvaI cleavage analysis confirmed the mutation in the
      patient. The two transition mutations observed in the two families also predict
      the conversion of arginine to a stop codon (R203X and R240X, respectively) around
      the homeodomain (HD), leading to the truncation of the PAX6 protein within its
      glycine-rich region. No abnormal SSCP bands or abnormal restriction fragments
      were detected in patients from the other two families. CONCLUSIONS: The two
      mutations sites identified in the two families, one at codon 203 and the other at
      codon 240, are those most frequently observed among 118 previously reported PAX6
      mutations. This indicates that the two mutations are two hot-spots in the gene.

PMID- 10887932
TI  - Branch retinal vein occlusion associated with the 20210 G-to-A prothrombin
      variant.
AB  - PURPOSE: To describe a case of branch retinal vein occlusion (BRVO) in a patient
      who tested positive for the 20210 A allele of the prothrombin (PT) gene. METHODS:
      A 48-year-old man had visual loss in the right eye secondary to BRVO confirmed by
      ophthalmoscopy and fluorescein angiography. His medical history was not
      remarkable for common risk factors for retinal occlusive diseases. RESULTS:
      Laboratory tests for hypercoagulability were positive for PT 20210 A variant. The
      patient's family tested negative for the PT variant. CONCLUSIONS: Laboratory
      tests for coagulopathy, including the PT 20210 A variant, should be added to the
      examination of patients with central or BRVO, especially if most common risk
      factors for thrombosis have been excluded.

PMID- 10887933
TI  - Bilateral non-arteritic anterior ischemic optic neuropathy in a patient with
      autoimmune thrombocytopenia.
AB  - PURPOSE: To describe a patient with bilateral non-arteritic anterior ischemic
      optic neuropathy (NAION) and idiopathic autoimmune thrombocytopenia (ITP) with an
      extremely low platelet count. METHOD: Case report. RESULTS: Remarkably good
      recovery of visual acuity. CONCLUSIONS: Bilateral non-arteritic anterior ischemic
      optic neuropathy can develop in the presence of a very low platelet count.

PMID- 10887934
TI  - Orbital lipogranuloma after sinus surgery.
AB  - PURPOSE: To report the treatment and histopathological findings in two cases who
      developed eyelid swelling, proptosis and diplopia due to orbital and lid
      lipogranuloma after endoscopic surgery of the maxillary and ethmoidal sinuses.
      METHODS: To relieve the proptosis and diplopia, debulking surgery was done on the
      eyelids and orbit. The tissue removed was sent for histopathological examination.
      RESULTS: The two patients improved after surgery. The eyelid swelling, proptosis
      and diplopia subsided and ocular movements became normal. Histopathologic
      examination disclosed an extensive lipogranuloma. CONCLUSIONS: Extensive orbital
      and eyelid lipogranuloma causing proptosis and diplopia is a rare complication of
      endoscopic sinus surgery, and can be relieved by surgical debulking.

PMID- 10887935
TI  - Drug-induced torsade de pointes: from molecular biology to bedside.
AB  - A progressively increasing number of cardiac and noncardiac drugs prolong the
      ventricular action potential duration (QT interval of the electrocardiogram) and
      cause a distinctive polymorphic ventricular tachycardia termed torsades de
      pointes (TdP) that can degenerate into ventricular fibrillation and sudden
      cardiac death. Drugs prolong the QT interval and cause TdP by blocking cardiac K+
      channels in general and selectively blocking the rapidly activating delayed
      rectifier channel IKr. Coassembly of HERG (human-ether-a-go-go-related gene)
      alpha-subunits and MiRP1 (MinK-related peptide 1) beta-subunits recapitulate the
      behavior of native human IKr and mutations of HERG and MiRP1 decrease the
      repolarizing current, delay ventricular repolarization and prolong the QT. Thus,
      drug-induced QT prolongation and TdP might represent an iatrogenic reproduction
      of the congenital LQTS. In patients with silent forms of the congenital LQTS
      associated with mutations in IKr, arrhythmic symptoms developed almost
      exclusively after exposure to QT-prolonging drugs. This review centers on the
      possible cellular mechanisms underlying drug-induced QT prolongation and TdP, the
      description of specific drugs and risk factors facilitating the development of
      TdP, and the recommendations for preventing and treating this potentially fatal
      arrhythmia.

PMID- 10887936
TI  - Capsaicin receptor in the pain pathway.
AB  - Capsaicin, the main pungent ingredient in 'hot' chili peppers, elicits burning
      pain by activating specific (vanilloid) receptors on sensory nerve endings. The
      cloned capsaicin receptor (VR1) is a nonselective cation channel with six
      transmembrane domains that is structurally related to a member of the TRP
      (transient receptor potential) channel family. VR1 is activated not only by
      capsaicin but also by increases in temperature that reach the noxious range (>43
      degrees C). Protons potentiate the effects of capsaicin or heat on VR1 activity
      by markedly decreasing the capsaicin concentration or temperature at which the
      channel is activated. Furthermore, a significant increase in proton concentration
      (pH <5.9) can evoke channel activity at room temperature. The analysis of single
      channel currents in excised membrane patches suggests that capsaicin, heat or
      protons gate VR1 directly. VR1 can therefore be viewed as a molecular integrator
      of chemical and physical stimuli that elicit pain. VRL-1, a VR1 homologue, is not
      activated by vanilloids or protons, but can be activated by elevation in ambient
      temperature exceeding 52 degrees C. These findings indicate that related ion
      channels may account for thermal responsiveness over a range of noxious
      temperature.

PMID- 10887937
TI  - Paeoniflorin, a major constituent of peony root, reverses muscarinic M1-receptor
      antagonist-induced suppression of long-term potentiation in the rat hippocampal
      slice.
AB  - We previously reported that paeoniflorin but not albiflorin, components of peony
      root, produced ameliorative effects on scopolamine-induced spatial cognitive
      impairment in rats. In this study, we examined the effects of paeoniflorin and
      muscarinic receptor antagonists on long-term potentiation (LTP) of population
      spike recorded from the CA1 region of rat hippocampal slices. Bath applications
      of an M1- and M2-receptor antagonist scopolamine and a selective M1-receptor
      antagonist pirenzepine, at a concentration of 10 microM, significantly suppressed
      LTP, whereas AF-DX116, a selective M2-receptor antagonist, failed to affect it.
      Paeoniflorin (0.1-1 microM), which alone was ineffective on LTP induction,
      significantly reversed the suppressive effects of scopolamine and pirenzepine (10
      microM). In contrast, albiflorin (0.1- 1 microM) had no effect on the scopolamine
      induced LTP suppression. These results suggest that paeoniflorin reversal of the
      muscarinic M1-receptor-mediated inhibition of LTP may be implicated in the
      ameliorative effect of paeoniflorin on spatial cognitive impairment caused by
      cholinergic dysfunction.

PMID- 10887938
TI  - Effects of acute and chronic administration of MCI-225, a new selective
      noradrenaline reuptake inhibitor with 5-HT3 receptor blocking action, on
      extracellular noradrenaline levels in the hypothalamus of stressed rats.
AB  - In the present study, we investigated the effects of acute and chronic systemic
      administration of MCI-225 (4-(2-fluorophenyl)-6-methyl-2-(1
      piperazinyl)thieno[2,3-d]pyrimidine monohydrate hydrochloride), a newly-developed
      selective noradrenaline (NA) reuptake inhibitor with 5-HT3-receptor-blocking
      action, on extracellular NA levels in the hypothalamus of stressed and non
      stressed rats by utilizing intracerebral microdialysis. Acute administration of
      MCI-225 (3 and 10 mg/kg, p.o.) significantly and dose-dependently increased
      extracellular NA levels in the hypothalamus in non-stressed rats. Footshock for
      20 min also significantly increased NA levels in the hypothalamus of both groups
      of rats pretreated with vehicle and MCI-225. Although chronic administration of
      MCI-225 (3 or 10 mg/kg, p.o. for 14 days) did not alter the basal extracellular
      NA levels in the hypothalamus, the stress-induced increases in extracellular NA
      levels were significantly lower in rats chronically treated with MCI-225 (10
      mg/kg) than those of rats pretreated with vehicle for the same period. The
      increase in extracellular NA levels induced by MCI-225 challenge (3 or 10 mg/kg,
      p.o.) were not different between rats chronically treated with MCI-225 or
      vehicle. These results suggest that MCI-225 enhances extracellular NA levels in
      the hypothalamus in both non-stressed and stressed rats by inhibiting NA uptake
      and that chronic systemic administration of MCI-225 did not alter basal
      extracellular NA levels, but reduced the increase in NA release caused by
      footshock stress. These data suggest the possibility that MCI-225 might possess
      anxiolytic and/or antidepressant properties.

PMID- 10887939
TI  - New approach for measurement of sympathetic nervous abnormality in conscious,
      spontaneously hypertensive rats.
AB  - We previously reported a highly sensitive chemiluminescence high-performance
      liquid chromatographic method to determine catecholamines in plasma. In this
      study, we employed this method to measure the cardiac function and plasma
      norepinephrine (NE) concentration in conscious rats. Benidipine, 1,4
      dihydropyridine calcium antagonist (4 mg/kg), and beta-blocker (propranolol, 30
      mg/kg) were administered orally to conscious spontaneously hypertensive rats
      (SHRs) and Wistar-Kyoto (WKY) rats, and blood pressure, heart rate and plasma NE
      levels were measured. Plasma NE concentration was used as an index of sympathetic
      nervous system activity in conscious rats. The basal plasma NE levels were
      significantly higher in SHRs than in WKY rats (P<0.05), indicating the activity
      of the basal sympathetic nervous system in SHRs was elevated. The sensitivity of
      the baroreflex-mediated sympathetic nervous response was reduced in SHRs as
      compared to that in WKY rats. The concomitant administration of benidipine and a
      beta-blocker decreased heart rate without affecting the baroreflex-mediated
      sympathetic nervous response, indicating that propranolol might suppress mainly
      the cardiac beta-adrenoceptor. The present study suggested the high activity of
      the basal sympathetic nervous system and the reduced response of the baroreflex
      mediated sympathetic nervous system in SHRs compared to WKY rats in the conscious
      condition.

PMID- 10887940
TI  - Vascular endothelial growth factor promotes cell-cycle transition from G0 to G1
      phase in subcultured endothelial cells of diabetic rat thoracic aorta.
AB  - Vascular endothelial growth factor (VEGF) has been claimed to be a major positive
      regulator of angiogenesis in diabetic retinopathy and atherosclerosis. Diabetic
      state-induced alteration of the phenotypes and the influence of 12-h pretreatment
      with VEGF were examined after a further 12-h treatment with only 1% fetal bovine
      serum in subcultured endothelial cells (EC) derived from rat thoracic aorta. By
      flow cytometric cell cycle analysis, VEGF showed quite different transition
      patterns from those of platelet-derived growth factor (PDGF) in 5-day (at the
      progression phase) cultured normal rat EC even though VEGF belongs to the PDGF
      family. VEGF promoted cell cycle transition from the G0 to the G1 phase at 3
      ng/ml, but at 30 ng/ml, VEGF weakly inhibited it compared with the effect of
      PDGF. The streptozotocin-diabetic state promoted cell cycle transition of EC from
      the G0 to the G1 phase. The promotion by the low concentration of VEGF was
      observed even at the point of 35-day culture (angiogenic EC at the competence
      phase in normal state). The diabetic state enhanced EC proliferation rather than
      tube formation, and the tube formation was scarce. The promotion of cell cycle
      transition by VEGF may aggravate furthermore diabetic angiopathy due to the leaky
      constitution of blood vessels.

PMID- 10887941
TI  - Effects of angiotensin-converting enzyme inhibitors on spontaneous or stimulated
      generation of reactive oxygen species by bronchoalveolar lavage cells harvested
      from patients with or without chronic obstructive pulmonary disease.
AB  - We examined the effects of angiotensin-converting enzyme (ACE) inhibitors on
      spontaneous or stimulated generation of reactive oxygen species (ROS) by
      bronchoalveolar lavage (BAL) cells prepared from 6 patients with chronic
      obstructive pulmonary disease (COPD) and from age-matched control subjects
      without COPD. The ROS produced by BAL cells were measured by the lucigenin
      dependent chemiluminescence method. The application of ACE inhibitors into
      culture media containing BAL cells inhibited spontaneous and stimulated
      generation of ROS by BAL cells from COPD patients and control subjects in an
      ambroxol-concentration-dependent manner. Alacepril, an ACE inhibitor bearing SH
      group, inhibited the oxygen radical production and generation by BAL cells from
      COPD patients in a dose-dependent fashion. Approximately 0.6-0.7 mM of alacepril
      inhibited 50% of the ROS production by BAL cells from COPD patients, whereas a
      slightly higher concentration (3 mM) of lisinopril, an ACE inhibitor not bearing
      an SH-group, was necessary to inhibit the production of ROS. These results
      suggest that an ACE inhibitor may act as an pulmonary antioxidant in patients
      with COPD.

PMID- 10887942
TI  - In vivo pharmacologic profile of YM158, a new dual antagonist for leukotriene D4
      and thromboxane A2 receptors.
AB  - The antagonistic activity of oral YM158 (3-[(4-tert-butylthiazol-2-yl)methoxy]-5'
      [3-(4-chlorobenzenesu lfonyl)propyl]-2'-(1H-tetrazol-5-ylmethoxy)benzanilide
      monosodium salt monohydrate), a new dual antagonist for leukotriene (LT) D4 and
      thromboxane (TX) A2 receptors, was investigated. Oral YM158 caused dose-dependent
      inhibition of LTD4-induced increases in plasma leakage and LTD4- or U46619
      induced increases in airway resistance, with ED50 values of 6.6, 8.6 and 14
      mg/kg, respectively. The dose-range of YM158's inhibitions was almost the same
      for both LTD4 and TXA2 receptors, and repeated oral doses did not affect its
      efficacy. Furthermore, oral YM158 inhibited antigen-induced bronchoconstriction.
      Although the potency of pranlukast for LTD4 receptor antagonism (ED50 = 0.34
      mg/kg) is greater than that of YM158 (ED50 = 8.6 mg/kg), the doses of both
      pranlukast and YM158 for significant inhibition of the antigen-evoked airway
      response were the same, indicating that the TXA2 receptor antagonism of YM158
      plays an important role in its anti-asthmatic effects. In conclusion, YM158
      promises to be a novel agent for treating bronchial asthma.

PMID- 10887943
TI  - Protective effect of TA-993, a novel therapeutic agent for peripheral circulatory
      insufficiency, on skeletal muscle fatigue in a rat model of hindlimb ischemia.
AB  - TA-993 (cis-(-)-2-(4-methylphenyl)-3-acetoxy-2,3-dihydro-5-(2-dimethylaminoethy
      l)-8-methyl1,5-benzothiazepine-4(5H)-one maleate), a new 1,5-benzothiazepine
      derivative, has a selective increasing action on limb blood flow in addition to
      an antiplatelet action. In this report we studied the effect of TA-993 on a time
      dependent decrease in developed tension of electrically-induced contraction of
      tibialis anterior muscle in a rat model of peripheral circulatory insufficiency
      induced by occlusion of abdominal aorta. In our preparation, the developed
      tension decreased by 20-30% in a sham-operated group and 30-40% in an abdominal
      aorta-occluded group at the end of the experimental period of 60 min.
      Intraduodenal administration (i.d.) of TA-993 (10 mg/kg) to the abdominal aorta
      occluded rats ameliorated the decrease in developed tension to the level of the
      sham-operated group. Moreover, TA-993 at 10 mg/kg, i.d. significantly increased
      femoral arterial blood flow supplied through collateral circulation and decreased
      the whole blood viscosity in this model. These results suggest that TA-993
      improves dysfunction of skeletal muscle contraction due to peripheral circulating
      insufficiency through an increase in collateral blood flow and an improvement of
      red blood cell deformability.

PMID- 10887944
TI  - Decrease of sexual receptivity by prolylendopeptidase inhibitor in female rats.
AB  - The effects of a prolylendopeptidase inhibitor, 1-[3-(2-indanylanylacetyl)-L
      thioprolyl]pyrrolidine (Z-321), on lordosis behavior were investigated in
      estrogen and progesterone-treated ovariectomized rats. Females were orally
      administered 100, 200 or 300 mg/kg Z-321 or the vehicle (control). The mean
      lordosis quotient in the rats given 300 mg/kg Z-321 was lower than that in
      control group, but that in rats given 100 or 200 mg/kg Z-321 was not lower. Thus,
      Z-321 suppressed lordosis in estrogen and progesterone-treated ovariectomized
      rats. Peptide neurotransmitters, especially those containing proline, are thought
      to be involved in the inhibitory mechanisms for lordosis behavior.

PMID- 10887945
TI  - Effects of zaldaride maleate, an antidiarrheal compound, on intracellular Ca2+
      mediated short-circuit current response in the rat colonic mucosa.
AB  - The effect of zaldaride maleate (ZAL) on intracellular Ca2+-mediated short
      circuit current (Isc) response in rat colonic mucosa was investigated. The Isc
      response to acetylcholine was partially reduced by the neuronal blocker
      tetrodotoxin. The tetrodotoxin-sensitive Isc response to acetylcholine was
      inhibited by ZAL. The tetrodotoxin-insensitive effect, which indicates direct
      stimulation of acetylcholine in colonic mucosa, was not affected by ZAL. The Isc
      response to the Ca2+ ionophore A23187 was reduced by ZAL in the presence of
      tetrodotoxin. These results suggest that ZAL reduces colonic ion secretion by
      inhibiting a tetrodotoxin-sensitive neuronal pathway and an intracellular Ca2+
      pathway in epithelium.

PMID- 10887946
TI  - Protease-activated receptor (PAR), a novel family of G protein-coupled seven
      trans-membrane domain receptors: activation mechanisms and physiological roles.
AB  - The protease-activated receptor (PAR) belongs to the large superfamily of G
      protein-coupled seven trans-membrane domain receptors. The activation of PARs is
      achieved by proteolytic unmasking of the cryptic N-terminal receptor-activating
      sequence that binds to the body of the same receptor molecule. PARs-1, -3 and -4
      are activated by thrombin, while PAR-2 is activated by trypsin or mast cell
      tryptase, but not by thrombin. PARs are widely distributed to a variety of
      tissues and participate in a number of physiological or pathophysiological
      phenomena such as platelet aggregation, inflammation and cardiovascular,
      digestive or respiratory functions. Thus, PARs are of physiological importance
      and also of pharmacological interest as the novel target for drug development.

PMID- 10887947
TI  - Enkephalinergic neurons in the periaqueductal gray and morphine withdrawal.
AB  - The effects of opioid (e.g., morphine) withdrawal on levels of endogenous opioid
      peptides and their mRNA in the various brain regions have been studied. However,
      the role of this opioidergic mechanism in the mediation of opioid withdrawal is
      not fully understood. Preproenkephalin (PPE) mRNA in the caudal periaqueductal
      gray (cPAG), an important brain region in opioid withdrawal, is increased by both
      opioid antagonist (naloxone)-precipitated and spontaneous morphine withdrawal,
      but not by various other stresses in rats, indicating a role of endogenous
      enkephalins in the cPAG in morphine withdrawal. In addition, PPE mRNA levels in
      the cPAG increase in the course of the dissipation of morphine withdrawal, and
      they are returned to the control levels after disappearance of morphine
      withdrawal signs. Local administration of an enkephalin analog or peptidase
      inhibitors into the cPAG suppresses morphine withdrawal signs. These facts
      suggest that enkephalinergic neurons in the PAG may have a critical role in the
      recovery phase of morphine withdrawal. Recently, an involvement of transcription
      factors in morphine withdrawal has been suggested. Thus, the possible role of
      transcription factors in the regulation of PPE gene expression in the cPAG during
      morphine withdrawal is also discussed.

PMID- 10887948
TI  - Purinoceptor-mediated calcium mobilization and cellular proliferation in cultured
      bovine corneal endothelial cells.
AB  - In the present study, we investigated the effect of adenosine triphosphate (ATP)
      on cytosolic free calcium mobilization and mitogenic activity in cultured bovine
      corneal endothelial cells (BCEC). The [Ca2+]i was determined using a Ca2+
      sensitive indicator, Fura-2/AM, and cell proliferation was evaluated by counting
      the cell number. ATP, its metabolites and analogs caused transient increase in
      [Ca2+]i in a concentration-dependent manner (10(-7) M-10(-3) M) and the potency
      of agonists was ordered as follows: 2-methylthio-ATP > uridine triphosphate > ATP
      > adenosine diphosphate. Adenosine monophosphate and adenosine did not affect
      [Ca2+]i. ATP (10(-4) M) also promoted the accumulation of inositol trisphosphate
      (IP3). The ATP-induced transient [Ca2+]i increase and IP3 accumulation were
      attenuated by pretreatment with a phospholipase C inhibitor, U-73122 (5 microM),
      for 30 min. ATP (10(-5) M) significantly enhanced the proliferation of BCEC. ATP
      induced [Ca2+]i increase and cell proliferation were inhibited by a purinoceptor
      antagonist, suramin (10(-4) M). Thus, the present study indicates that BCEC
      contain P2 purinoceptors that regulate their proliferation.

PMID- 10887949
TI  - Antiplatelet and antithrombotic effects of a novel selective phosphodiesterase 3
      inhibitor, NSP-513, in mice and rats.
AB  - We investigated the effects of NSP-513, (R)-4,5-dihydro-5-methyl-6-[4-(2-propyl-3
      oxo-1-cyclohexenyl)amino] phenyl-3(2H)-pyridazinone, on phosphodiesterase (PDE)
      isozyme activities, in vitro platelet aggregation and in vivo thrombus formation.
      NSP-513 selectively inhibited human platelet PDE 3 isozyme with an IC50 value of
      0.039 microM. In an in vitro human platelet aggregation assay, the IC50 values
      (microM) of NSP-513 for platelet aggregation induced by collagen, U-46619,
      arachidonic acid, adenosine diphosphate (ADP), epinephrine and thrombin were
      0.31, 0.25, 0.082, 0.66, 0.23 and 0.73, respectively. In a mouse pulmonary
      thromboembolism model, orally administered NSP-513 showed in vivo antithrombotic
      effects that were 320 to 470 times more potent than those of cilostazol. In a rat
      carotid arterial thrombosis model, intraduodenally administered NSP-513 (0.1
      mg/kg), cilostazol (30 mg/kg) and aspirin (30 mg/kg) reduced thrombus formation
      by 75%, 66% and 48%, respectively. However, intravenously administered
      dipyridamole (10 mg/kg) did not significantly prevent thrombus formation. These
      results demonstrate that NSP-513 has the potential to prevent not only in vitro
      platelet aggregation but also in vivo thrombus formation and indicate that the
      highly selective PDE 3 inhibitory effect of NSP-513 may make this compound useful
      for assessing the physiological role of PDE 3.

PMID- 10887950
TI  - Protective effect of benidipine against the abnormal electrical activity in
      single ventricular myocytes of the guinea pig under simulated ischemic conditions
      and reperfusion.
AB  - Induction of electrical abnormalities (EAs) under simulated ischemic conditions
      and after reperfusion was measured from single cardiac myocytes isolated from
      guinea pig ventricle using whole-cell voltage or current clamp with perforated
      patch variation. Conditions of simulated ischemia were produced by the exchange
      of medium from the standard one oxygenated with 95% O2-5% CO2 gas (pH 7.4) to the
      modified one, which contained no glucose, 8 mM K+ and 30 mM sodium-D,L-lactate
      and was gassed with 90% argon-10% CO2 (pH 6.6). Under the simulated ischemia for
      20 min, EAs such as delayed afterdepolarization, early afterdepolarization,
      automatic activity or transient inward current were observed in about 37% of
      myocytes driven electrically at 1 Hz. Irreversible hypercontracture occurred in
      myocytes of 10% or less. Upon reperfusion with the standard solution, EAs and
      hypercontracture were observed in about 43% and 22% of cells, respectively.
      Glibenclamide-sensitive current was detected during ischemia, but tended to be
      enhanced during reperfusion. Amplitude of Ca2+ current and ATP-sensitive K+
      current after reperfusion varied widely with time and from cell to cell. When
      myocytes were pretreated for 10 min with 10 nM benidipine, a 1,4-dihydropyridine
      derivative Ca2+ blocker, the incidence of EAs and hypercontracture was markedly
      reduced, suggesting the protective effect of benidipine against cardiac cell
      injury during ischemia and reperfusion.

PMID- 10887951
TI  - Protein kinase C potentiates capacitative Ca2+ entry that links to
      steroidogenesis in bovine adrenocortical cells.
AB  - I investigated the role of protein kinase C (PKC) in regulation of the
      capacitative Ca2+ entry and steroidogenesis in bovine adrenocortical (BA) cells.
      Thapsigargin (TG)-treatment depleted intracellular Ca2+ stores followed by
      induction of Ca2+ influx from the extracellular pool and also increasing of Mn2+
      influx as an indicator of divalent cation influx in BA cells. Calphostin C, a PKC
      inhibitor, inhibited the TG-induced [Ca2+]i elevation dose-dependently (0.1-1
      microM) and attenuated Mn2+ entry. Phorbol 12-myristate 13-acetate (PMA), an
      activator of PKC, potentiated the elevation of [Ca2+]i and enhanced Mn2+ entry by
      TG treatment. These results suggest that PKC may modulate capacitative Ca2+ entry
      in BA cells. In the presence of extracellular Ca2+, TG enhanced cortisol
      production in BA cells. Calphostin C attenuated the TG-induced steroidogenesis
      dose-dependently (0.25-1 microM). PMA enhanced the steroidogenesis dose
      dependently (1-100 nM). These results suggested that PKC may have a modulatory
      effect on the capacitative Ca2+ entry that links to steroidogenesis in BA cells.

PMID- 10887952
TI  - Anti-ulcer effects of chitin and chitosan, healthy foods, in rats.
AB  - In this study, we compared the effects of low molecular weight (LMW) chitosan
      (MW: 25,000-50,000), high molecular weight (HMW) chitosan (MW: 500,000-1000,000)
      and chitin on ethanol-induced gastric mucosal injury and on the healing of acetic
      acid-induced gastric ulcers in rats. Oral administration of LMW chitosan (250,
      500 and 1000 mg/kg) dose-dependently prevented ethanol-induced gastric mucosal
      injury. Repeated oral administration of LMW chitosan (100, 200 and 400 mg/kg
      twice daily) also dose-dependently accelerated the gastric ulcer healing.
      However, the effects of HMW chitosan and chitin on the gastric mucosal injury
      formation and the gastric ulcer healing were less potent than those of LMW
      chitosan. LMW chitosan (250 and 500 mg/kg, orally) was ineffective in inhibiting
      gastric acid secretion in pylorus-ligated rats, although it had a weak acid
      neutralizing action. LMW-chitosan (250, 500 and 1000 mg/kg orally) dose
      dependently prevented the decrease in gastric mucus content induced by ethanol.
      These results indicate that of the three compounds, LMW chitosan has the most
      potent gastric cytoprotective and ulcer healing-promoting actions. In addition,
      gastric mucus-increasing action of LMW-chitosan may be, at least in part, related
      to the anti-ulcer effect of this compound.

PMID- 10887953
TI  - U-46619, a selective thromboxane A2 mimetic, inhibits the release of endogenous
      noradrenaline from the rat hippocampus in vitro.
AB  - Possible roles of thromboxane A2 (TXA2) in the release mechanism of hippocampal
      noradrenaline (NA) were examined in vitro. Slices or crude synaptosomes prepared
      from the rat hippocampus were superfused with modified Krebs-Ringer solution.
      Application of 20 mM KCl for 5 min increased the release of NA from the slices,
      and this release was consistently reproduced. Application of U-46619 (9,11
      dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F2alpha), a specific TXA2
      mimetic, just before the second KCl (20 mM) stimulation decreased the KCl-evoked
      NA release in a concentration-dependent manner (10-100 microM). This U-46619 (50
      microM)-induced inhibition of NA release was abolished by 10 microM SQ29548, a
      specific TXA2 receptor antagonist. In experiments with hippocampal crude
      synaptosomes, however, KCl (20 and 40 mM)-evoked release of NA was not attenuated
      by U-46619 (100 microM). Furthermore, the inhibitory effect of U-46619 (50
      microM) in the sliced preparations was not modified by 100 microM (-)
      bicuculline, a GABA(A)-receptor antagonist. The present results indicate that U
      46619 inhibits the release of NA from the rat hippocampus by activation of TXA2
      receptors. Activation of TXA2 receptors probably excites an unidentified but not
      GABAergic neuron system, thereby inhibiting the NA release from the rat
      hippocampus.

PMID- 10887954
TI  - Intestinal cytochrome P450 and response to rifampicin in rabbits.
AB  - Properties of cytochrome P450 (P450) in rabbit intestines have been investigated
      to assess the possibility of an experimental model for human intestinal oxidation
      of drugs. Significant amounts of P450 and cytochrome b5 and activities of NADPH
      cytochrome P450 reductase were detected in microsomes from rabbit duodenal,
      jejunal, ileac and colon mucosa. All the small intestinal fractions mediated
      phenytoin, dextromethorphan and testosterone oxidations. Several P450 forms
      belonging to the CYP1A, CYP2C, CYP2D and CYP3A, but not CYP2B and CYP2E,
      subfamilies were detected in these tissues by Western blotting. A good
      correlation was observed between immunodetectable levels of CYP3A and activities
      of testosterone 6beta-hydroxylation. Small intestine, but not colon, CYP3A levels
      were increased by the pretreatment of rabbits with rifampicin (50 mg/kg for 4
      days, p.o.). The extent of the increase was similar between duodena and livers.
      These properties of rabbit intestinal P450s were comparable to those of human
      intestine. These phenomena suggest the possibility that the rabbit is a
      beneficial in vivo model for the assessment of drug interaction occurring at the
      first pass of drugs ingested.

PMID- 10887955
TI  - Bone anabolic effects of PTH(1-34) and salmon calcitonin in ovariectomy- and
      ovariectomy-steroid-induced osteopenic rats: a histomorphometric and
      biomechanical study.
AB  - Using an experimental model of type 1 osteoporosis under the chronic therapy with
      an anti-inflammatory steroid, the bone anabolic effect of PTH(1-34) was evaluated
      by histomorphometrical and biomechanical analysis. Wistar female rats (12-week
      old) were ovariectomized and allowed to develop an osteopenic model in the
      presence or absence of methylprednisolone acetate (MPA: 0.1 mg/kg, s.c., 3-days-a
      week basis from the 5th week after ovariectomy (OVX)). The osteopenia that
      developed for the first 12 weeks after OVX was almost completely normalized by
      subsequent PTH pulsing (20 microg/kg, s.c., 5-days-a-week) for 8 weeks starting
      at the 13th week; the following characteristics were observed: 1) proximal tibial
      metaphysis: recovered bone volume, rather increased trabecular thickness and
      osteoid volume, and normalized eroded surface; 2) 5th lumbar vertebra (L-5):
      partially recovered trabecular connectivity; 3) femur and 4th lumbar vertebra (L
      4): recovered mechanical strength in maximum elastic load and maximum elastic
      energy. The anabolic effect of PTH(1-34) was not substantially modified by MPA.
      Salmon calcitonin (SCT: 10 U/kg per day, s.c., 5-days-a-week, for 8 weeks) was
      anabolic in limited parameters: decreased number of osteoclasts, recovered
      maximum elastic load in femur, and partially recovered maximum elastic load in L
      4. The results suggest that PTH(1-34) pulsing is able to recover OVX-induced
      osteopenia in the structure and mechanical strength not only of the cancellous
      bone but also of the cortical bone, and the anabolic effect can be clinically
      expected even under steroid medication.

PMID- 10887956
TI  - The Chinese herbal medicine Chai-Hu-Long-Ku-Mu-Li-Tan (TW-001) exerts
      anticonvulsant effects against different experimental models of seizure in rats.
AB  - We evaluated the anticonvulsant effect of Chai-Hu-Long-Ku-Mu-Li-Tan (TW-001), a
      Chinese herbal medicine, and its mechanisms in several standard rodent models of
      generalized seizure. TW-001 (4 g/kg, p.o.) significantly increased the threshold
      for tonic electroconvulsions and the threshold for tonic seizures in response to
      i.v. infusion of pentylenetetrazole (PTZ). In the s.c. PTZ seizure test, both the
      incidence and severity of seizures were decreased by TW-001. TW-001 (1-10 mg/ml)
      did not alter resting membrane potential or input resistance of the hippocampal
      CA1 neurons, but elicited a reversible suppression of stimulus-triggered
      epileptiform activity in area CA1 and spontaneously occuring epileptiform burst
      discharges in area CA3 elicited by picrotoxin. Both field excitatory postsynaptic
      potentials and population spikes were reversibly depressed by TW-001 (0.5-15
      mg/ml) in a concentration-dependent manner. The sensitivity of postsynaptic
      neurons to a glutamate-receptor agonist, alpha-amino-3-hydroxy-5-methylisoxazole
      4-propionic acid or N-methyl-D-aspartate, was not altered by TW-001 (10 mg/ml).
      However, TW-001 (5 mg/ml) clearly increased the magnitude of paired-pulse
      facilitation. TW-001 (5-10 mg/ml) reversibly limited the repetitive firing and
      reduced the maximal rate of rise of action potentials elicited by injection of
      depolarizing current pulses (0.4 nA, 200 ms) into the pyramidal cells. TW-001 (1
      10 mg/ml) exerted a concentration-dependent reduction of the tetrodotoxin
      sensitive sodium currents and high voltage-activated calcium currents. These
      results suggest that TW-001 is an interesting new anticonvulsant agent that
      exerts its anticonvulsant activity through inhibition of sodium and calcium
      channels, stabilizing neuronal membrane excitability and inhibiting glutamate
      release.

PMID- 10887957
TI  - Effects of nitric oxide scavenger, carboxy-PTIO on endotoxin-induced alterations
      in systemic hemodynamics in rats.
AB  - The present experiments were conducted to clarify the mode of cardiovascular
      action of carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy
      PTIO), a nitric oxide (NO) scavenger, during rat endotoxic shock by determining
      cardiac output and systemic arterial tone simultaneously. Lipopolysaccharide
      (LPS) (10 mg/kg, i.v.) decreased systemic blood pressure and cardiac output with
      transient increases in hematocrit and total vascular resistance. Administration
      of carboxy-PTIO (1.7 mg x kg(-1) x min(-1), i.v. for 60 min) at 90 min after LPS
      attenuated further decline in blood pressure and cardiac output without affecting
      changes in hematocrit or total vascular resistance. It is concluded that carboxy
      PTIO attenuates endotoxin-induced hypotension predominantly by maintaining
      cardiac output in rat experimental endotoxic shock.

PMID- 10887958
TI  - Reversal of multidrug resistance in human leukemia K562 by tamolarizine, a novel
      calcium antagonist.
AB  - A new type of organic Ca2+ channel blocker, tamolarizine, was examined for its
      reversing effect on multidrug-resistant tumor cells. Tamolarizine synergistically
      potentiated the cytotoxicity of doxorubicin for doxorubicin-resistant K562 cells
      (K562/DXR) at a concentration of 0.1-10 microM, but had hardly any synergistic
      effects in the parental cell line (K562) at the same concentration. Moreover,
      tamolarizine inhibits the P-glycoprotein pump-efflux activity in a dose-related
      manner and reduces the expression of the immunoreactive P-glycoprotein in
      K562/DXR cells as evaluated by cytofluorimetric assay. These results indicate
      that tamolarizine reverses the multidrug-resistance phenotype through direct
      interaction with P-glycoprotein.

PMID- 10887959
TI  - Inhibition of microtubule polymerization by SK&F 96365, a blocker of receptor
      linked Ca2+ entry.
AB  - SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl]-1H-imid
      azole hydrochloride) is widely used as an effective inhibitor of receptor-linked
      and capacitative Ca2+ entry. Since this inhibitor has additional effects such as
      inhibition of voltage-dependent Ca2+ channels, sarco- and endoplasmic reticula
      Ca2+ pumps and cell proliferation, its molecular mechanism of action remains to
      be solved. In the present study, we have investigated the effect of SK&F 96365 on
      microtubule protein isolated from bovine brain in vitro. SK&F 96365 depolymerized
      the polymerized microtubules in a concentration-dependent manner. This result
      suggests that SK&F 96365 directly depolymerizes microtubules, an effect that may
      contribute to the various actions of this compound.

PMID- 10887960
TI  - Localization of glucocorticoid hormone receptors in mitochondria of human cells.
AB  - Glucocorticoid hormones regulate the transcription of nuclear genes by way of
      their cognate receptors. In addition, these hormones also modulate mitochondrial
      gene transcription by mechanisms which are as yet poorly understood. Using
      immunofluorescence labeling and confocal laser scanning microscopy we show that
      the glucocorticoid receptor of HeLa and Hep-2 cells is specifically enriched at
      the sites of the mitochondria which were visualized by labeling with the vital
      dye CMX and antibodies against cytochrome oxidase subunit I. Immunogold electron
      microscopy demonstrated that the receptor was located within the inner space of
      the mitochondria. Immunoblotting experiments also revealed the presence of
      glucocorticoid receptor in mitochondria isolated from HeLa and Hep-2 cells.
      Finally, living HeLa cells expressing green fluorescent-glucocorticoid receptor
      fusion protein revealed a distinct mitochondrial GFP fluorescence. Our results
      support the concept of a receptor-mediated direct action of steroid hormones on
      mitochondrial gene transcription.

PMID- 10887961
TI  - Expression of Rab small GTPases in epithelial Caco-2 cells: Rab21 is an apically
      located GTP-binding protein in polarised intestinal epithelial cells.
AB  - Rab proteins belong to a subfamily of small GTP-binding protein genes of the Ras
      superfamily and play an important role in intracellular vesicular targeting. The
      presence of members of this protein family was examined in Caco-2 cells by a PCR
      based strategy. Twenty-five different partial cDNA sequences were isolated,
      including 18 Rab protein family members. Seven novel human sequences,
      representing Rab2B, Rab6A', Rab6B, Rab10, Rab19B, Rab21 and Rab22A, were
      identified. For one clone, encoding Rab21, full-length cDNA was isolated from a
      Caco-2 cDNA library. Northern blot analysis showed a ubiquitous expression
      pattern of Rab21. To study Rab21 protein expression in Caco-2 cells, polyclonal
      antibodies were raised against GST-Rab21 fusion protein and characterised. The
      antibodies recognised Rab21 as a protein of approximately 25 kDa. Interestingly,
      the protein shows a general ER-like staining in nonpolarised Caco-2 cells in
      contrast to an apically located vesicle-like staining in polarised Caco-2 cells.
      Furthermore, immunohistochemical staining on human jejunal tissue showed a
      predominant expression of Rab21 in the epithelial cell layer with high expression
      levels in the apical region, whereas stem cells in the crypts were negative. We
      therefore suggest an alternative role for Rab21 in the regulation of vesicular
      transport in polarised intestinal epithelial cells.

PMID- 10887962
TI  - Uniform apicobasal polarity of microtubules and apical location of gamma-tubulin
      in polarized intestinal epithelium in situ.
AB  - Polarized differentiation of the intestinal epithelium has been previously shown
      to depend on an intact microtubular system that is essential for vectorial
      delivery of apical membrane proteins to the apical cell surfaces. Uniform
      alignment and polarization of microtubules have been suggested to provide the
      ultrastructural basis for vectorial transport between the Golgi apparatus and the
      apical cell surface. In the present study we applied the hook decoration
      technique to analyse the polarity of microtubules in the rat jejunal epithelium.
      By immunocytochemistry we studied the subcellular location of gamma-tubulin, an
      essential component of microtubule-organizing centers. Microtubules were found to
      be mainly aligned parallel to the apicobasal axis of the cells and to extend from
      the subterminal space underneath the apical terminal web down to the cellular
      basis. We found that 98% out of 1122 decorated microtubules displayed uniform
      apicobasal polarity with the growing ends (plus ends) pointing basally and the
      non-growing ends (minus ends) pointing towards the cellular apex. No differences
      were observed with respect to microtubular polarity between the apical,
      perinuclear and infranuclear cellular portions. Immunostaining specific for gamma
      tubulin was restricted to the apical subterminal space underneath the rootlets of
      microvilli. These findings indicate that the apical subterminal space of
      enterocytes serves as the predominant if not exclusive microtubule-organizing
      compartment from which uniformly polarized microtubules grow out with their plus
      ends towards the cellular basis.

PMID- 10887963
TI  - Myelin basic protein component C1 in increasing concentrations can elicit fusion,
      aggregation, and fragmentation of myelin-like membranes.
AB  - Myelin basic protein (MBP) is considered to have a primary role in the formation
      and maintenance of the myelin sheath. Many studies using artificial vesicle
      systems of simple lipid composition, and generally small size, have shown that
      MBP can elicit vesicle fusion, aggregation, or even fragmentation under different
      conditions. Here, we have studied the effects of increasing concentrations of
      bovine MBP charge isomer C1 (MBP/C1) on large unilamellar vesicles (LUVs)
      composed of phosphatidylcholine and phosphatidylserine (92:8 molar ratio), or
      with a lipid composition similar to that of the myelin membrane in vivo (Cyt
      LUVs). Using absorbance spectrophotometry, fluorescence resonance energy
      transfer, dynamic light scattering and transmission electron microscopy, we have
      shown that vesicle aggregation and some vesicle fusion occurred upon addition of
      MBP/C1, and as the molar protein-lipid ratio increased. Fragmentation of Cyt-LUVs
      was observed at very high protein concentrations. These results showed that the
      phenomena of vesicle fusion, aggregation, and fragmentation can all be observed
      in one in vitro system, but were dependent on lipid composition and on the
      relative proportions of protein and lipid.

PMID- 10887964
TI  - Identification of the universal cofactor (auxilin 2) in clathrin coat
      dissociation.
AB  - Uncoating of clathrin-coated vesicles in neuronal cells requires hsc70 in concert
      with the cofactor auxilin which contains a J-domain as well as a domain with
      homology to dual specific phosphatases and tensin, known as PTEN. The question of
      whether an analogous factor operates in other cell types has until now remained
      unanswered. Here we show that it is the recently discovered and widely expressed
      cyclin G-associated protein kinase which fulfils the function of neuronal auxilin
      in hsc70-mediated clathrin coat dissociation. GAK possesses a J-domain, which
      stimulates the hsc70 ATPase, it competes with auxilin for clathrin binding and at
      sufficiently high concentrations acts as a clathrin assembly protein. Moreover,
      GAK binds to the gamma- and alpha-appendage domains of the adaptor proteins AP-1
      and AP-2 in vitro and phosphorylates their medium chains. Cells that transiently
      overexpress GAK are impaired in respect of receptor-mediated endocytosis. In
      transfected cells clathrin is dislodged from coated pits/vesicles and co
      localizes with GFP-GAK in the form of large aggregates. The cellular distribution
      of membrane-associated adaptors was unaffected by overexpression of GAK. Our
      results point to a hsc70/auxilin-based uncoating system as a ubiquitous feature
      of eukaryotic cells.

PMID- 10887965
TI  - Caveolin isoforms in resident and elicited rat peritoneal macrophages.
AB  - Caveolin--an integral membrane protein--is the principal component of caveolae
      membranes in vivo. Multiple forms of caveolin have been identified: caveolin
      1alpha, caveolin-1beta, caveolin-2 and caveolin-3. They differ in their specific
      properties and tissue distribution. When we studied the lysate of resident and
      elicited macrophages isolated from rat peritoneal cavity by Western blot
      analysis, we identified two different proteins (approximately 29 kDa and
      approximately 20 kDa) which were labelled with anti-caveolin antibodies. The
      approximately 20-kDa protein was labelled specifically only by anti
      VIP21/caveolin-1, while the approximately 29-kDa protein was labelled by anti
      VIP21/caveolin-1 and anti-caveolin-2. The presence of the approximately 29-kDa
      protein was characteristic of resident macrophages, and only a small amount of
      the approximately 20-kDa protein was detected in these cells. Elicitation
      resulted in a significant increase in the amount of the approximately 20-kDa
      protein labelled by anti-VIP21/caveolin-1 only. According to its molecular mass
      and antibody-specificity, this protein might be identical with the caveolin-1beta
      isoform. Our morphological (confocal and electron microscopical) studies have
      shown that in resident cells caveolin was present in the cytoplasm, in smaller
      vesicles and multivesicular bodies around the Golgi area. Only a very small
      amount of caveolae was found on the surface of these cells. In elicited
      macrophages, caveolae (labelled with the anti-VIP21/caveolin-1 antibody) appeared
      in large numbers on the cell surface, but caveolin detected by anti-caveolin-2
      was also found in small vesicles and multivesicular bodies in the cytoplasm.
      According to these results, the absence of caveolae in resident cells can be
      explained by the absence of caveolin-1. The expression of the approximately 29
      kDa (caveolin-related) protein in resident macrophages seems to be insufficient
      for caveolae formation. Elicitation significantly increased the expression of
      caveolin-1, and the increased amount of caveolin-1 resulted in caveolae formation
      on the cell surface.

PMID- 10887966
TI  - Cloning and characterization of beta-COP from Dictyostelium discoideum.
AB  - We have isolated a cDNA coding for beta-COP from Dictyostelium discoideum by
      polymerase chain reaction using degenerate primers derived from rat beta-COP. The
      complete cDNA clone has a size of 2.8 kb and codes for a protein with a
      calculated molecular mass of 102 kDa. Dictyostelium beta-COP exhibits highest
      homology to mammalian beta-COP, but it is considerably smaller due to a shortened
      variable region that is thought to form a linker between the highly conserved N-
      and C-terminal domains. Dictyostelium beta-COP is encoded by a single gene, which
      is transcribed at moderate levels into two RNAs that are present throughout
      development. To localize the protein, full-length beta-COP was fused to GFP and
      expressed in Dictyostelium cells. The fusion protein was detected on vesicles
      distributed all over the cells and was strongly enriched in the perinuclear
      region. Based on coimmunofluorescence studies with antibodies directed against
      the Golgi marker comitin, this compartment was identified as the Golgi apparatus.
      Beta-COP distribution in Dictyostelium was not brefeldin A sensitive being most
      likely due to the presence of a brefeldin A resistance gene. However, upon DMSO
      treatment we observed a reversible disassembly of the Golgi apparatus. In
      mammalian cells DMSO treatment had a similar effect on beta-COP distribution.

PMID- 10887967
TI  - Nuclear localization of procaspase-9 and processing by a caspase-3-like activity
      in mammary epithelial cells.
AB  - Caspases are aspartate-specific proteases that are specifically activated by
      numerous death stimuli. Caspase activation is thought to play a major role for
      the execution of apoptosis. Inactive caspase-9 zymogen is known to be localized
      within the mitochondrial intermembrane space where it is involved in monitoring
      mitochondrial damage-associated cytochrome c release and subsequent activation of
      procaspase-3. Here we show that in mammary epithelial cell lines a significant
      fraction of caspase-9 proform is associated with discrete structures in the
      nucleus. Stimulation of cells with chemotherapeutic agents leads to the
      processing of nuclear procaspase-9 and to the accumulation of nuclear and
      cytoplasmic caspase activity. Using cell-free extracts from caspase-3-deficient
      MCF-7 cells we show that caspase-8-mediated processing of nuclear procaspase-9
      requires caspase-3. In caspase-3-expressing breast cancer cells, cytochrome c
      induced processing of nuclear procaspase-9 is blocked by the caspase inhibitors z
      VAD and DEVD but not by YVAD. Purified active caspase-3 is sufficient to cleave
      nuclear caspase-9 zymogen. These results suggest that, in addition to the
      mitochondrial localization, caspase-9 proform is found within the nucleus and its
      processing can be regulated by caspase-3.

PMID- 10887968
TI  - Ultrastructure of nuclei of cisplatin-treated C6 glioma cells undergoing
      apoptosis.
AB  - C6 glioma cells, treated with a cytostatic dose of cisplatin (1.66 x 10(-5) M)
      ceased dividing by 24 h and, most of them had undergone apoptosis by 72-96 h. The
      reactive cells were classified into 5 types (T-I to V), according to the
      ultrastructure of nuclei. At 4 h, 20.4% of cells (T-I) showed minute condensation
      and margination of chromatin. The nuclear envelope (NE) formed slim and deep
      invaginations consisting of the inner or both membranes. The later kind of NE
      invaginations often extended to the enlarged nucleoli and contained nucleolus
      like material at its cytoplasmic side. Some nuclear pores were covered with a
      dome-shaped "cap" formed by fine filamentous material. The number of T-I cells
      increased to 53.3% by 72 h. In T-II cells, which appeared at 24 h, the chromatin
      was condensed into dense irregular masses separated from the NE by a lucent space
      with filamentous structures preventing complete margination of chromatin.
      Nucleoli of T-II cells were small and showed partial segregation of their
      components. The "capped" pores were absent in these apparently more damaged
      cells. From 24 h, cells with large and lobulated nuclei (T-III) started to
      increase in number and peaked at 72 h (6.6%). Except for some small lobules, the
      chromatin of T-III cells was moderately aggregated and the NE was well preserved.
      Typical apoptotic cells with highly condensed and marginated chromatin (T-IV)
      peaked at 48-72 h (2.4-4.8%). They appeared in 2 varieties, including cells with
      wrinkled nuclei with less condensed and incompletely marginated chromatin or more
      lobulated forms with highly condensed marginated chromatin suggesting their
      origin from T-II or T-III cells. T-IV cells, as well as their fragments,
      underwent phagocytosis and secondary necrosis (T-V cells, 48.6% at 96 h). Two
      alternative routes of nuclear changes leading to cisplatin-triggered apoptosis,
      as represented by the sequence T-I --> T-III --> T-IV/V or T-I --> T-II --> T
      IV/V, may explain the initially less or more damaged cells. These alternatives,
      together with progressive recruitment of reactive cells, suggest intrapopulation
      differences in the sensitivity of cells or in the cell cycle perturbations
      induced by cisplatin. Except for the T-IV and T-V cells, observed alterations of
      cytoplasmic organelles, including mitochondria, were fewer than reported in
      previous studies on cisplatin.

PMID- 10887969
TI  - Factors involved in the absence of sedative effects by the second-generation
      antihistamines.

PMID- 10887970
TI  - The clinical efficacy of antihistamines in the skin.

PMID- 10887971
TI  - The advantages for an H1 antihistamine of a low volume of distribution.

PMID- 10887973
TI  - Clinical use of antihistamines in infants and children at risk of asthma
      development.

PMID- 10887972
TI  - Evaluation of the cardiac safety of second-generation antihistamines.

PMID- 10887974
TI  - CNS effects in the correct perspective.

PMID- 10887975
TI  - Comparing the H1 profile of second-generation antihistamines.

PMID- 10887976
TI  - The metabolic profile of second-generation antihistamines.

PMID- 10887977
TI  - The clinical relevance of the anti-inflammatory properties of antihistamines.

PMID- 10887979
TI  - Opportunities and challenges in clinical research.

PMID- 10887978
TI  - Sex differences in schizophrenia, a review of the literature.
AB  - OBJECTIVE: To comprehensively and critically review the literature on gender
      differences in schizophrenia. METHOD: An initial search of MEDLINE abstracts
      (1966-1999) was conducted using the terms sex or gender and schizophrenia,
      followed by systematic search of all relevant articles. RESULTS: Males have
      consistently an earlier onset, poorer premorbid functioning and different
      premorbid behavioral predictors. Males show more negative symptoms and cognitive
      deficits, with greater structural brain and neurophysiological abnormalities.
      Females display more affective symptoms, auditory hallucinations and persecutory
      delusions with more rapid and greater responsivity to antipsychotics in the
      premenopausal period but increased side effects. Course of illness is more
      favorable in females in the short- and middle-term, with less smoking and
      substance abuse. Families of males are more critical, and expressed emotion has a
      greater negative impact on males. There are no clear sex differences in family
      history, obstetric complications, minor physical anomalies and neurological soft
      signs. CONCLUSION: This review supports the presence of significant differences
      between schizophrenic males and females arising from the interplay of sex
      hormones, neurodevelopmental and psychosocial sex differences.

PMID- 10887980
TI  - Assessment of the value of the vertebral heart scale in the radiographic
      diagnosis of cardiac disease in dogs.
AB  - In order to assess the influence of the vertebral heart scale (VHS) on the
      accuracy of the radiographic diagnosis of cardiac disease, thoracic radiographs
      of 50 dogs with proven cardiac disease, 26 with other thoracic diseases, and 50
      with no clinical signs of cardiovascular or respiratory disease were mixed and
      examined by three independent, blinded observers chosen to represent a range of
      radiographic abilities. They first examined all the radiographs without making
      measurements of VHS and made a diagnosis. They then re-examined the radiographs,
      and measured VHS on both lateral and dorsoventral or ventrodorsal radiographs
      before again recording a diagnosis without reference to their original diagnoses.
      For all the observers, the dogs with cardiac disease had a higher mean VHS than
      the normal dogs. A VHS over 10.7 on the lateral radiograph was a moderately
      accurate sign of cardiac disease. The observers' accuracy of diagnosis did not
      change significantly as a result of using VHS as an adjunct to a subjective
      assessment of the radiographs.

PMID- 10887981
TI  - Identification of morbilliviruses of probable cetacean origin in carcases of
      Mediterranean monk seals (Monachus monachus).
AB  - Two morbilliviruses were isolated from carcases of Mediterranean monk seals
      (Monachus monachus) which had died in coastal areas of Greece and Mauritania.
      They were characterised as being closely related to the previously identified
      dolphin and porpoise morbilliviruses on the basis of their serological cross
      reactivities in immunofluorescence assays, and sequence homologies in their N and
      P genes. The results suggest that morbilliviruses of aquatic mammals may cross
      barriers between species of different orders.

PMID- 10887982
TI  - Economic aspects of outbreaks of dermatophilosis in first-calving cows in nine
      herds of dairy cattle in Israel.
AB  - Outbreaks of dermatophilosis in nine herds of dairy cattle in Israel were studied
      retrospectively. The outbreaks might have been associated with the exposure of
      the animals to intense showering during the spring and summer months of May to
      October, in addition to calving and postcalving stress. The acute exudative form
      of dermatophilosis occurred in the first-calving cows during the six weeks after
      they calved. The morbidity rate ranged from 10.0 to 66.6 per cent and the period
      of morbidity ranged from eight to 19 days. Mortality or culling occurred in four
      of the herds and ranged from 1.6 to 17.1 per cent. The disease also resulted in a
      gradual loss of condition, a decrease in milk production and marked increases in
      the somatic cell counts in milk.

PMID- 10887983
TI  - Masticatory and skeletal muscle myositis in canine leishmaniasis (Leishmania
      infantum).
AB  - Twenty-four dogs with a parasitologically and serologically established diagnosis
      of leishmaniasis were studied to investigate the atrophy of the masticatory
      muscles which commonly occurs in this disease, and to compare the lesions in the
      masticatory muscles with those in the cranial tibial muscles. The 24 animals were
      divided into three groups of eight, group A dogs with no muscular atrophy, group
      B dogs with different degrees of atrophy in the masticatory and skeletal muscles,
      and group C dogs with similar degrees of atrophy in the masticatory and skeletal
      muscles. Increased activities of creatine phosphokinase and lactate dehydrogenase
      were recorded in only some of the dogs in groups B and C, but there were no
      significant differences between the mean activities in the three groups.
      Electromyographic changes indicating myopathy and involving both the temporalis
      and cranial tibial muscles, were observed in two of the dogs in group A, seven of
      those in group B, and in all the dogs in group C. Muscle histopathology revealed
      a variable degree of muscle fibre necrosis and atrophy, mononuclear infiltrates
      and neutrophilic vasculitis in all the dogs except two in group A. Leishmanial
      amastigotes were found within macrophages and myofibres in 16 of the dogs, some
      in each group. IgG immune complexes were detected in muscle samples, and
      circulating antibodies against myofibres were detected in serum samples from all
      the 24 dogs.

PMID- 10887984
TI  - Antimicrobial resistance in enteric porcine Escherichia coli strains in Spain.

PMID- 10887985
TI  - Naturally occurring bovine leukosis virus in water buffalo (Bubalus bubalis) in
      Brazil.

PMID- 10887986
TI  - Serum thyrotropin response to TRH administration in six healthy beagle dogs.

PMID- 10887987
TI  - TB and animal husbandry.

PMID- 10887988
TI  - Adder bites in dogs and cats.

PMID- 10887989
TI  - PCV-2-associated PDNS in Northern Ireland in 1990. Porcine dermatitis and
      nephropathy syndrome.

PMID- 10887990
TI  - Certificate in veterinary dermatology.

PMID- 10887991
TI  - Use of lignocaine.

PMID- 10887992
TI  - Antibiotic resistance: government accepts the recommendations from the ACMSF.
      Advisory Committee on the Microbiological Safety of Food.

PMID- 10887993
TI  - Potential benefits of canine genetic screening.

PMID- 10887994
TI  - New requirements in practice: matching services to changing demands.

PMID- 10887995
TI  - Parasite control methods used by horse owners: factors predisposing to the
      development of anthelmintic resistance in nematodes.
AB  - One hundred and fifty horse owners, primarily private owners and riding schools,
      replied to a questionnaire concerning the practices they used to control
      parasites. Twenty-seven had experienced a parasite problem. Faecal samples from
      188 horses selected at random showed that worm control practices were generally
      successful; however, many owners were not following recommendations for slowing
      the development of resistant parasites. In 1996, 86 per cent of the owners were
      using either three or two classes of anthelmintic a year, and they used a median
      of six doses with a range from one to 11. Approximately half the owners, more
      commonly owners of up to five horses, picked up their horses' faeces at least
      once a week, but these owners also used more doses of anthelmintic a year than
      owners who did not pick up faeces. One-third of the owners manually removed
      Gasterophilus species eggs from the horses' hairs, but 94 per cent of them also
      used ivermectin. Many owners treated specifically for Anoplocephala species,
      cyathostome larvae and Gasterophilus species, and these owners were the most
      likely to use three classes of anthelmintic a year. One-hundred-and-seven owners
      replied to a second questionnaire asking for information about the factors that
      influenced their anthelmintic control practices. Many owners, particularly
      private owners, were not influenced by the cost of the anthelmintic. For the
      timing and frequency of treatment, and the choice of drug, owners were most
      influenced by advertisements, magazine articles and veterinary surgeons. In two
      magazines aimed at horse owners, the brands of drugs most frequently advertised
      were the brands most commonly used by the owners, and articles in the magazines
      recommended the use of three classes of drug per year. These results are
      discussed in relation to their influence on the development of anthelmintic
      resistant nematodes.

PMID- 10887996
TI  - GM1 gangliosidosis in shiba dogs.
AB  - A six-month-old shiba dog with a one-month history of progressive motor
      dysfunction showed clinical signs of a cerebellar disorder, including ataxia,
      dysmetria and intention tremor of the head. Histopathological and ultrastructural
      studies revealed distended neurons packed with membranous cytoplasmic bodies
      throughout the central nervous system. The activities of lysosomal acid beta
      galactosidase in its leucocytes and liver were less than 2 per cent of the
      control levels, and the compound accumulated in the brain was identified as GM1
      ganglioside. A sibling which died immediately after birth was shown to have a
      beta-galactosidase deficiency in the brain and visceral organs. A family study
      revealed that the sire and dam of the probands were heterozygotes with
      approximately half of the normal level of beta-galactosidase activity, suggesting
      an autosomal recessive pattern of inheritance.

PMID- 10887998
TI  - Cardiomyopathy syndrome in farmed Scottish salmon.

PMID- 10887997
TI  - Diagnosis of Lyme disease in two cows by the detection of Borrelia burgdorferi
      DNA.
AB  - Two cows from different herds in a district of Switzerland known to harbour
      ixodid ticks had erythematous lesions on the hairless skin of the udder, were in
      poor general condition with a poor appetite and decreased milk production, and
      had a stiff gait and swollen joints. Borrelia burgdorferi sensu strictu DNA was
      detected in samples of synovial fluid and milk from one of the cows and Borrelia
      afzelii DNA was detected in synovial fluid from the other by means of a real-time
      PCR.

PMID- 10887999
TI  - MRI findings in a dog with otitis media and suspected otitis interna.

PMID- 10888000
TI  - Ornithobacterium rhinotracheale infection in Japan: preliminary investigations.

PMID- 10888001
TI  - Activity of closantel against adult triclabendazole-resistant Fasciola hepatica.

PMID- 10888002
TI  - Surveillance for scrapie.

PMID- 10888003
TI  - Surveillance for scrapie.

PMID- 10888004
TI  - Pet Travel Scheme.

PMID- 10888005
TI  - Pet Travel Scheme.

PMID- 10888006
TI  - Olympic Games 2000: certification regarding Borna disease in horses.

PMID- 10888007
TI  - Bovine TB.

PMID- 10888008
TI  - Costs of procedures.

PMID- 10888009
TI  - Hot off the press.

PMID- 10888010
TI  - The influence of natural products upon drug discovery.

PMID- 10888011
TI  - Marine polyether triterpenes.

PMID- 10888012
TI  - Beta-phenylethylamines and the isoquinoline alkaloids.

PMID- 10888013
TI  - The biosynthesis of shikimate metabolites.

PMID- 10888014
TI  - The structure elucidation and biological activities of high molecular weight
      algal toxins: maitotoxin, prymnesins and zooxanthellatoxins.

PMID- 10888015
TI  - Assessing the value of structured protocols for forensic interviews of alleged
      child abuse victims.
AB  - OBJECTIVE: To evaluate the effectiveness of a structured interview protocol
      (NICHD Investigative Interview Protocol) operationalizing universally recommended
      guidelines for forensic interviews. METHOD: The NICHD Investigative Protocol was
      designed to maximize the amount of information obtained using recall memory
      probes, which are likely to elicit more accurate information than recognition
      memory probes. Forensic investigators were trained to use the NICHD protocol
      while conducting feedback-monitored simulation interviews. The utility of the
      protocol was then evaluated by comparing 55 protocol interviews with 50 prior
      interviews by the same investigators, matched with respect to characteristics
      likely to affect the richness of the children's accounts. The comparison was
      based on an analysis of the investigators' utterance types, distribution, and
      timing, as well as quantitative and qualitative characteristics of the
      information produced. RESULTS: As predicted, protocol interviews contained more
      open-ended prompts overall as well as before the first option-posing utterance
      than non-protocol interviews did. More details were obtained using open-ended
      invitations and fewer were obtained using focused questions in protocol
      interviews than in non-protocol interviews, although the total number of details
      elicited did not differ significantly. In both conditions, older children
      provided more details than younger children did. CONCLUSION: The findings
      confirmed that implementation of professionally recommended practices affected
      the behavior of interviewers in both the pre-substantive and substantive phases
      of their interviews and enhanced the quality (i.e., likely accuracy) of
      information elicited from alleged victims.

PMID- 10888016
TI  - Counseling sexually abused girls: the impact of sex of counselor.
AB  - OBJECTIVE: The present study was conducted to assess the impact of sex of
      counselor on the therapeutic process for sexually abused girls in individual
      counseling. METHOD: Raters evaluated videotapes of counseling sessions recorded
      for 35 sexually abused girls who had been systematically assigned to brief-term
      psychoeducationally oriented treatment with either a male or female counselor.
      Clients' in-session behavior was rated using accepted therapeutic process
      measures, while statistically controlling for the effect of girls' pretreatment
      comfort level with male and female counselors. RESULTS: Overall, MANCOVA results
      revealed that girls' participation in counseling was not significantly related to
      session number, the child's age (i.e., preadolescent vs. adolescent), or the sex
      of counselor who provided treatment services. However, univariate results and
      graphic representations of girls' behavior suggest that adolescent clients, when
      compared with their preadolescent counterparts, seemed to be more reluctant to
      discuss certain child sexual abuse topics. CONCLUSIONS: The findings suggest that
      caution is warranted regarding categorical recommendations on the assignment of
      young female survivors to male counselors. Delimitations and limitations of the
      study and directions for future research are discussed.

PMID- 10888017
TI  - Linking childhood sexual abuse and abusive parenting: the mediating role of
      maternal anger.
AB  - OBJECTIVE: This study had two primary objectives: First, to examine the
      association between childhood sexual abuse (CSA) and later parenting
      characteristics, particularly physical abuse potential, and second, to explore
      maternal anger as a mediator of the relationship between CSA and adult physical
      abuse potential. METHOD: Utilized a community sample of low SES participants that
      included 138 mothers classified as having experienced CSA, and a comparison group
      of 152 non-sexually abused mothers. Parenting variables examined included the
      mothers' physical abuse potential, nurturance toward their children, unrealistic
      developmental expectations of children, as well as frequencies of spanking and
      general punishment. Data was collected via interview and other self-report
      measures. RESULTS: Even after controlling for mothers' childhood experience of
      Physical abuse, CSA significantly predicted adult risk of physically abusing
      one's own children. Further, maternal anger was confirmed as a mediator of the
      relationship between having been sexually abused as a child and the potential for
      physically abusing one's own children. CONCLUSIONS: CSA may be a risk factor for
      subsequent physically abusive parenting, while anger appears to play a
      significant role in mediating this relationship. Findings are discussed in the
      context of current knowledge concerning the impact of child sexual abuse and the
      processes contributing to abusive parenting.

PMID- 10888018
TI  - [Resilience factors in the victims of sexual abuse: state of affairs].
AB  - OBJECTIVE: The aim of this literature review is to examine factors leading to the
      recovery of child sexual abuse survivors. METHOD: This paper provides a
      definition of resilience and presents the individual and environmental protective
      factors. A methodological examination of the studies is carried through. RESULTS:
      Researchers have documented that 20% to 44% of adult who were sexually abused
      during their childhood show no apparent signs of negative outcome. However, very
      few studies as been interested in resilient women and their protective
      mechanisms. Recent research on protective factors reveal that searching for
      support, disclosing the abuse and giving a meaning to the abuse are all
      adaptative cognitive strategies. Furthermore, the perception of benefits and
      having an external attributional style are both related to less psychological
      distress. Social support, in general and after the revelation, also appears as a
      determinant of resilience. However, avoidance, even if victims find it very
      useful, proves to be a non-adaptative strategy, which may lead to be a catalyst
      to victims' symptomatology. Definitional problems and the lack of longitudinal
      studies limit the conclusions that can be drawn. CONCLUSION: The rare studies
      involving resilient victims show that social support as well as certain cognitive
      coping strategies may lead to recovery. However the extent of their contribution
      remains unknown.

PMID- 10888019
TI  - Physiological correlates of childhood abuse: chronic hyperarousal in PTSD,
      depression, and irritable bowel syndrome.
AB  - OBJECTIVE: During the past 10 years, researchers have documented how trauma-
      especially severe trauma--can alter the functioning of the brain. In some cases,
      these alterations create a state of chronic hyperarousal. The present review
      serves as an introduction to this research. FINDINGS: Persons who have
      experienced traumatic events are often "primed" to over-react to subsequent
      stressors, making them more vulnerable to these events. CONCLUSION: Chronic
      hyperarousal underlies three common and often co-occurring sequelae of childhood
      abuse: post-traumatic stress disorder (PTSD), depression, and irritable bowel
      syndrome. Knowledge of these physiological correlates can affect treatment
      decisions as well as our theories about the mechanisms underlying the development
      of symptoms.

PMID- 10888020
TI  - Using video vignettes to evaluate children's personal safety knowledge:
      methodological and ethical issues.
AB  - OBJECTIVE: The study aimed to assess children's personal safety knowledge by
      seeking their responses to video-delivered simulations of child maltreatment.
      METHOD: In seeking to do this, methodological and ethical difficulties were
      encountered. These arose during several phases of consultation, the refinement of
      an interview protocol to be used with the vignettes, and during discussions over
      the ethical integrity of the research. RESULTS: Using visually graphic vignettes
      to probe children's personal safety knowledge proved to be methodologically
      difficult and ethically problematic and controversial. The main objections to the
      approach were that it could harm participants, and that parents needed extensive
      information about the study to exercise "informed consent." CONCLUSIONS: The
      study demonstrated the nature and extent of negotiations that were needed to
      "push the boundaries" of evaluation research to develop more valid, authentic and
      complex ways of accessing children's thinking about personal safety concepts and
      strategies.

PMID- 10888021
TI  - Childhood sexual abuse history and role reversal in parenting.
AB  - OBJECTIVE: This study explored the main and interactive effects of sexual abuse
      history and relationship satisfaction on self-reported parenting, controlling for
      histories of physical abuse and parental alcoholism. METHOD: The community sample
      consisted of 90 mothers of 5- to 8-year-old children. The sample was limited to
      those mothers currently in an intimate relationship, 19 of whom reported a
      history of childhood sexual abuse. Participants completed the Child Behavior
      Checklist, the Parenting Stress Inventory, the Family Cohesion Index, and
      questions assessing parent-child role reversal, history of abuse and parental
      alcoholism, and current relationship satisfaction. RESULTS: Results of analyses
      and multivariate analyses of covariance suggested that sexual abuse survivors
      with an unsatisfactory intimate relationship were more likely than either sexual
      abuse survivors with a satisfactory relationship or nonabused women to endorse
      items on a questionnaire of role reversal (defined as emotional overdependence
      upon one's child). Role reversal was not significantly predicted by histories of
      physical abuse or parental alcoholism or child's gender. While parenting stress
      was inversely predicted by the significant main effect of relationship
      satisfaction, neither parenting stress nor child behavior problems were predicted
      by the main effect of sexual abuse history or by the interaction between sexual
      abuse history and relationship satisfaction. CONCLUSIONS: These results suggest
      the unique relevance of sexual abuse history and relationship satisfaction in the
      prediction of a specific type of parent-child role reversal--namely, a mother's
      emotional overdependence upon her child.

PMID- 10888022
TI  - Coping strategies and burnout among veteran child protection workers.
AB  - OBJECTIVES: First, to learn how veteran (2 years or more) child protective
      service (CPS) investigations workers cope with job stress; and secondly, to
      examine the relationship between coping strategies and levels of emotional
      exhaustion, depersonalization, and sense of reduced personal accomplishment
      (burnout syndrome). METHOD: Cross-sectional, self-report methodology was used to
      measure coping strategies and the burnout syndrome. The voluntary subjects were
      151 front-line CPS workers with at least 2 years experience in a southeastern
      Department of Social Services. They attended one of nine stress management
      workshops provided in various locations around the state. Quantitative analyses
      were run on the data. RESULTS: These workers perceived themselves to use Engaged
      (active) coping strategies more than Disengaged (avoidant) strategies. Sixty-two
      percent of participants scored in the high range on Emotional Exhaustion, the
      aspect some researchers consider to be the heart of Burnout. Those who used
      Engaged coping were less likely to feel depersonalized and more likely to feel a
      sense of personal accomplishment. Those who used Disengaged coping were more
      likely to feel emotionally exhausted, depersonalized, and to have a sense of
      reduced personal accomplishment. CONCLUSION: Neither the use of active nor
      avoidant coping strategies saved these workers from Emotional Exhaustion. The
      problem-focused strategies they are taught and use most do not help deal with the
      emotional content and context of their work, suggesting the use of emotion
      focused coping to prevent and remediate burnout.

PMID- 10888023
TI  - Revealing the existence of child abuse in the context of marital breakdown and
      custody and access disputes.
AB  - OBJECTIVE: Child abuse in the context of legal and de facto marital breakdown has
      received little attention internationally. Many believe it does not exist in this
      context and regard it as just a "gambit in the divorce wars." Recently, however,
      family courts in a number of countries have become concerned over the management
      of child abuse allegations in custody and access cases, known more commonly now
      as residence and contact cases. This article presents a unique research study,
      which investigated how the Family Court of Australia dealt with such cases. The
      study, covering all forms of child abuse, sought to discover who were the
      families bringing these problems to family courts, what precisely the abuse was
      and how the courts dealt with it. METHOD: The study reviewed court records of
      some 200 families where child abuse allegations had been made in custody and
      access disputes in jurisdictions in two states, observed court proceedings and
      interviewed court and related services' staff. RESULTS: The findings showed that
      these cases had become a core component of the court's workload without any
      public or professional awareness of this change, that the abuse was real, that it
      was severe and serious, and that the courts and child protection services did not
      provide appropriate services to the families. CONCLUSION: A new specialized
      intervention system was developed based on the research and it is now being
      trialed and evaluated. The new intervention system contains features derived from
      the research findings that may be suitable internationally for implementation.

PMID- 10888024
TI  - [Isolation of Gardnerella vaginalis in the diagnosis of sexual abuse in
      children].
AB  - INTRODUCTION: The study of sexual transmitted diseases is more and more frequent
      in patient with suspicion of sexual abuse, and this help to the final medical
      diagnosis. Organisms like Neisseria gonorrhoeae and Treponema indicate a sure
      sexual contact. However the role of the rest of organisms in the sexual abuse is
      more difficult of specifying. OBJECTIVE: To know the role of the Gardnerella
      vaginalis in the diagnosis of sexual abuse in patient with this possible
      diagnosis. METHODS: Retrospective study of 135 girls with suspicion of abuse,
      visited from May of 1997 to February of 1998. Vaginal swabs were taken from 45 of
      135 girls evaluated. RESULTS: In five patients the vaginal culture were positive
      to Gardnerella. The characteristics of these five patients are described (age,
      aggressor, type and duration of the abuse, physical exploration and final
      diagnosis). All our patients were the pubertal or prepubertal girls. In these
      patients the final diagnosis settled with the clinical history and the physical
      exploration, without keeping in mind the result of the culture. CONCLUSION: It is
      necessary to discard sexual abuse in all prepubertal girl with a positive culture
      with Gardnerella vaginalis, being difficult to specify the value of the
      Gardnerella in the adolescent patients.

PMID- 10888025
TI  - Child abuse in China: the views and experiences of child health professionals.

PMID- 10888026
TI  - Trauma: the impact of post-traumatic stress disorder.
AB  - Trauma has an enormous impact on both individuals and society as a whole.
      Recognition of the extent of this impact by the medical profession has been
      relatively slow but, with our growing appreciation of the prevalence of trauma
      exposure in civilian as well as combat populations, the true scale of trauma
      related psychiatric consequences is beginning to emerge. It has been reported
      that more than 60% of men and 51% of women experience at least one traumatic
      event in their lifetimes. Of these, 8% and 20%, respectively, fall victim to post
      traumatic stress disorder (PTSD) indicating that more women are at risk for
      developing PTSD. Individuals experience severe psychiatric stress that is
      compounded by significant comorbid illness. This impacts critically upon quality
      of life resulting in grave functional and emotional impairment. In addition,
      there is a detrimental cost to society with high financial and social
      consequences from the significantly elevated rates of hospitalization, suicide
      attempts and alcohol abuse.

PMID- 10888027
TI  - Fear: the impact and treatment of social phobia.
AB  - Social phobia is the most common anxiety disorder in the community with a
      prevalence rate in the range of 5-8%. The problem most often emerges in childhood
      or adolescence. Individuals with generalized social phobia are at risk of
      developing other psychiatric disorders such as major depression, alcohol abuse
      and other anxiety disorders. Sufferers of social phobia often do not seek
      treatment until they encounter difficulty with comorbid disorders. Recent
      research indicates that social anxiety disorder is associated with higher levels
      of disability and greater reductions in quality of life than previously
      understood, with difficulties encountered in social relationships, education and
      employment. In previous years, there has been little or no known available
      effective treatment, and the disorder frequently goes unrecognized in primary
      care. However, new pharmacological (selective serotonin reuptake inhibitors,
      SSRIs) and psychological treatments are emerging that are able to produce
      significant symptom reduction and improvements in functioning and quality of
      life. In recent years, the SSRIs have been the focus of considerable research and
      are becoming one of the first-line treatments for social phobia. Early
      intervention in social phobia may improve quality of life, reduce disability and
      reduce the development of comorbid disorders.

PMID- 10888028
TI  - Panic: course, complications and treatment of panic disorder.
AB  - Panic disorder is a chronic condition typically associated with significant
      distress and disability. In addition to the acute distress associated with the
      panic attack itself, the disorder often leads to distressing anticipatory anxiety
      and phobic avoidance. Affected individuals experience significant impairment in
      social and vocational functioning, high utilization of medical resources,
      constriction of function, premature mortality and diminution in overall quality
      of life. Panic disorder is frequently comorbid with other conditions,
      particularly depression, as well as alcohol and other substance abuse, and other
      anxiety disorders including social phobia, generalized anxiety disorder,
      obsessive-compulsive disorder and post-traumatic stress disorder. A number of
      pharmacological agents and cognitive-behavioural treatments have been shown to be
      effective in the treatment of panic disorder, with the selective serotonin
      reuptake inhibitors (SSRIs) becoming first-line pharmacotherapy for this
      condition. Among these, the SSRI sertraline appears effective not only in
      improving symptoms of panic, but also in reducing anticipatory anxiety and
      improving multiple aspects of quality of life. For patients who remain partly or
      fully symptomatic despite adequate first-line treatment, a variety of strategies
      are emerging for the management of refractory conditions. We provide an overview
      of the prevalence, presentation and associated complications of panic disorder,
      review the therapeutic options and discuss the management of refractory patients.

PMID- 10888029
TI  - Obsessions: the impact and treatment of obsessive-compulsive disorder in children
      and adolescents.
AB  - In the development of the majority of children, ritualistic behaviour may be seen
      as a normal phenomenon. In some children and adolescents, however, these rituals
      become time-consuming, interfering, irritating and annoying. The most common
      obsessions in both children and adults with obsessive-compulsive disorder (OCD)
      are related to a fear of dirt and contamination, fear of some terrible happening,
      and the fear of harming a loved one. The most common compulsions are washing
      fixations, checking behaviour and rituals (including mental rituals). Prevalence
      studies show that OCD in children and adolescents is far more common than
      previously thought. It is estimated that up to 2% of this population have
      symptoms fulfilling OCD criteria. The impact of early OCD onset can be profound,
      with long-term studies indicating that approximately 50% of these patients will
      also suffer from OCD in early adulthood. These patients tend to remain socially
      isolated, to have fewer relationships than their non-OCD peers, and have a
      tendency to remain within the family home during early adulthood. In addition,
      childhood OCD is associated with comorbid psychiatric disorders, in particular
      depression, anxiety and panic disorders, Tourette's syndrome and eating
      disorders. Treatment strategies for childhood OCD reflect those used in adult
      psychiatry. The most effective psychotherapeutic approach is based on cognitive
      behavioural therapy with exposure and prevention. In contrast to
      pharmacotherapeutic agents without serotonin activity, the serotonin-specific
      antidepressants appear to be effective and well-tolerated in the treatment of OCD
      in children.

PMID- 10888030
TI  - Impulsivity.
AB  - Disorders characterized by impulsivity include disorders of impulse control
      (intermittent explosive disorder, pyromania, kleptomania, pathological gambling
      and trichotillomania), paraphilias, sexual impulsions and sexual addictions and
      impulsive aggression personality disorders (borderline, antisocial, histrionic
      and narcissistic personality disorders). Impulsivity has a substantial impact on
      both individuals and society. Impulse control disorders may be conceptualized as
      a subset of the obsessive-compulsive spectrum. In this article, we examine the
      genetic and neurobiological aetiology of these disorders and possible treatment
      options. The link between serotonergic dysfunction and the pathophysiology of
      impulsivity is discussed, and studies that examine the efficacy of various
      selective serotonin reuptake inhibitors and other alternatives in the treatment
      of impulsive disorders such as pathological gambling, sexual addictions and
      borderline personality disorder are presented.

PMID- 10888031
TI  - Protein kinase antagonists: interim challenges and issues.

PMID- 10888032
TI  - Site-directed irreversible inhibitors of the erbB family of receptor tyrosine
      kinases as novel chemotherapeutic agents for cancer.
AB  - The erbB family of tyrosine kinases represents a versatile set of four plasma
      membrane receptors that possesses enormous diversity in signaling capability. The
      rationale to target this receptor system as an approach to cancer chemotherapy
      has continued to become more compelling with time. Both preclinical and clinical
      data strongly support the involvement of these receptors in the formation and
      progression of human cancers as well as establish a high correlation in cancer
      patients between receptor/ligand expression and poor prognosis. During the past 4
      years significant progress has been made in the area of epidermal growth factor
      receptor tyrosine kinase inhibitors and new structural classes have emerged that
      exhibit enormous improvements with regard to potency, specificity, and in vitro
      and in vivo efficacy. More recent advancements in this field have resulted in the
      discovery of very specific, irreversible inhibitors of the erbB family that
      provide unique pharmacological properties and exceptional efficacy. The in vivo
      performance of these modern kinase inhibitors has improved to the point where
      several compounds are either in clinical trials or very near to that point in
      their development. This article will provide a brief biological review of the
      erbB family and the justification for targeting this receptor family in cancer
      therapeutics, and then highlight some of the more promising kinase antagonists
      with emphasis on irreversible inhibitors.

PMID- 10888033
TI  - PKC412--a protein kinase inhibitor with a broad therapeutic potential.
AB  - The staurosporine derivative PKC412 was originally identified as an inhibitor of
      protein kinase C (PKC) and subsequently shown to inhibit other kinases including
      the kinase insert domain receptor (KDR) (vascular endothelial growth factor
      receptor, VEGF-R2), the receptor of platelet-derived growth factor, and the
      receptor for the stem cell factor, c-kit. PKC412 showed a broad antiproliferative
      activity against various tumor and normal cell lines in vitro, and was able to
      reverse the Pgp-mediated multidrug resistance of tumor cells in vitro. Exposure
      of cells to PKC412 resulted in a dose-dependent increase in the G2/M phase of the
      cell cycle concomitant with increased polyploidy, apoptosis and enhanced
      sensitivity to ionizing radiation. PKC412 displayed a potent antitumor activity
      as single agent and was able to potentiate the antitumor activity of some of the
      clinically used cytotoxins (Taxol and doxorubicin) in vivo. The combined
      treatment of PKC412 with loco-regional ionizing irradiation showed significant
      antitumor activity against tumors which are resistant to both ionizing radiation
      and chemotherapeutic agents (dysfunctional p53). The finding that PKC412 is an
      inhibitor of the VEGF-mediated cellular signaling via inhibition of KDR and PKC
      in vitro is consistent with the in vivo inhibition of VEGF-dependent angiogenesis
      in a growth factor implant model. Orally administered PKC412 also strongly
      inhibited retinal neovascularization as well as laser-induced choroidal
      neovascularization in murine models. In summary, PKC412 may suppress tumor growth
      by inhibiting tumor angiogenesis in addition to directly-inhibiting tumor cell
      proliferation via its effects on PKC and/or other protein kinases. PKC412 is
      currently in Phase I clinical trials for treatment of advanced cancer as well as
      for the treatment of ischemic retinopathy.

PMID- 10888034
TI  - Development of SU5416, a selective small molecule inhibitor of VEGF receptor
      tyrosine kinase activity, as an anti-angiogenesis agent.
AB  - Angiogenesis, or the sprouting of new blood vessels, is a central process in the
      growth of solid tumors. For many cancers, the extent of vascularization of a
      tumor is a negative prognostic indicator signifying aggressive disease and
      increased potential for metastasis. Recent efforts to understand the molecular
      basis of tumor-associated angiogenesis have identified several potential
      therapeutic targets, including the receptor tyrosine kinases for the angiogenic
      factor vascular endothelial growth factor (VEGF). Here we review the approach
      taken at SUGEN, Inc. to discover and develop small molecule inhibitors of
      receptor tyrosine kinases as anti-angiogenic agents. We focus on SU5416, a
      selective inhibitor of VEGF receptors that is currently in clinical development
      for the treatment of advanced malignancies. Its biochemical, biological and
      pharmacological properties are reviewed and clinical implications discussed.

PMID- 10888035
TI  - UCN-01 (7-hydroxystaurosporine) and other indolocarbazole compounds: a new
      generation of anti-cancer agents for the new century?
AB  - UCN-01 (7-hydroxystaurosporine) is a protein kinase inhibitor which is under
      development as an anti-cancer agent in the USA and Japan. Although UCN-01 was
      originally isolated from the culture broth of Streptomyces sp. as a protein
      kinase C-selective inhibitor, its ultimate target as an anti-cancer agent remains
      elusive. As a single agent, UCN-01 exhibits two key biochemical effects, namely
      accumulation of cells in the G1 phase of the cell cycle and induction of
      apoptosis. Both these effects may be important for its anti-cancer activity. As a
      modulator, UCN-01 enhances the cytotoxicity of other anti-cancer drugs such as
      DNA-damaging agents and anti-metabolite drugs through putative abrogation of G2
      and/or S phase accumulation induced by these anti-cancer agents. Currently, in
      addition to UCN-01, four other indolocarbazole anti-cancer drugs-two protein
      kinase inhibitors, CGP 41251, CEP-751, and two DNA-damaging agents, NB-506 and a
      Rebeccamycin analog-are undergoing clinical investigations in the USA, Europe or
      Japan. In this review, we would like to address the differences and similarities
      of these indolocarbazole compounds as anti-cancer agents with regard to their
      mechanism(s) of action, the effects on cell cycle progression, induction of
      apoptosis and modulation of drug sensitivity.

PMID- 10888036
TI  - Structure-based design modifications of the paullone molecular scaffold for
      cyclin-dependent kinase inhibition.
AB  - A congeneric series of paullones were characterized using a 3-D QSAR with cyclin
      dependent kinase 1 (CDK1) inhibition data. A homology model of CDK1-cyclin B was
      developed from the crystal structure of CDK2-cyclin A, which subsequently served
      as the basis for the structure-based design. Paullones were docked into the ATP
      binding site of the CDK1-cylin B models and were optimized with molecular
      mechanics. Hydropathic analyses of the paullone-CDK1 complexes were performed
      after the atom types were assigned based on each ligand's electronic properties
      calculated from quantum mechanics. Hydropathic descriptors formed a significant
      multiple regression equation that predicts paullone IC50 data. The results
      indicate that the combination of hydropathic descriptors with molecular mechanics
      geometries are sufficient to design overt steric and chemical complementarity of
      the ligands. However, the electronic properties derived from quantum mechanics
      helped direct synthetic chemistry efforts to produce ligands that promote better
      charge transfer and strengthen hydrogen bonding as facilitated by resonance
      stabilization. Compounds with low affinity for CDK1 were poor charge acceptors
      and made less than ideal hydrogen bonding arrangements with the receptor. These
      considerations led to the prediction that structures such as 9-cyanopaullone
      would be considerably more potent than the parent compound, a finding supported
      by enzyme inhibition data. Also, 9-nitropaullone emerged as a paullone which also
      had similar potency in enzyme inhibition as well as a favorable anti
      proliferative activity profile in living cells.

PMID- 10888037
TI  - Inhibition of N-linked glycosylation down-regulates insulin-like growth factor-1
      receptor at the cell surface and kills Ewing's sarcoma cells: therapeutic
      implications.
AB  - The insulin-like growth factor-1 receptor (IGF-1R) has been shown to be of
      critical importance for tumor development and tumor cell survival of various
      types of malignancies. We have previously demonstrated that an adequate N-linked
      glycosylation of IGF-1R is required for its translocation to the cell surface in
      melanoma cells. This raises the possibility of using glycosylation inhibitors as
      therapeutic agents against IGF-1R-dependent malignancies. In this study we show
      that inhibition of N-linked glycosylation using tunicamycin or the 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin resulted in
      down-regulation of IGF-1R at the cell surface in Ewing's sarcoma cell lines (RD
      ES and ES-1 cells). The down-regulation of plasma membrane-bound IGF-1R was
      correlated with a drastic decrease in IGF-1R autophosphorylation, suggesting
      biochemical inactivation of the receptor. Whereas RD-ES and ES-1 cells responded
      differently with regard to DNA synthesis, the decrease in IGF-1R expression was
      accompanied by a rapid and substantial decrease in survival of both cell lines.
      Our data suggest that relatively untoxic HMG-CoA reductase inhibitors (e.g.
      lovastatin) could have therapeutic significance in IGF-1R-dependent neoplasms
      like Ewing's sarcoma.

PMID- 10888038
TI  - A rational design of bioactive taxanes with side chains situated elsewhere than
      on C-13.
AB  - The structure of alphabeta-tubulin was refined and used in the docking study for
      taxuspine D, paclitaxel and their analogues. The conformational space in the
      binding site was explored by molecular dynamics. The interaction energy was
      calculated by minimization in the active site of beta-tubulin. The C-5 cinnamoyl
      side chain in taxuspine D is found to mimic the C-13 side chain of paclitaxel. A
      virtual taxane with a new C-5 side chain is predicted to be more active than
      taxuspine D. The C-13 side chain could be replaced with a novel C-5 side chain if
      the conformation of the core skeleton is modified.

PMID- 10888039
TI  - Treatment results of chemoradiation for T1 esophageal cancer with lymph node
      metastases.
AB  - PURPOSE: We clinically evaluated 12 patients with advanced superficial esophageal
      cancer who had undergone chemoradiotherapy. PATIENTS AND METHODS: A retrospective
      analysis was performed between October 1992 and December 1998 on 12 patients with
      M1 metastasis in lymph nodes or direct invasion of enlarged lymph nodes (A3) to
      adjacent structures. Combined treatment with radiotherapy and chemotherapy was
      applied to all patients. High-dose cisplatin (CDDP) and 5-fluorouracil (5-FU)
      were administered to five patients, low-dose CDDP and 5-FU to five patients, and
      others to two patients. Ten patients were treated by external irradiation alone,
      and two patients were treated by external and intracavitary irradiation. RESULTS:
      Of the 12 patients, the response of the primary tumor to this therapy resulted in
      11 CRs (91.6%) and one PR, while the response of the largest metastatic lesion in
      lymph nodes in each patient resulted in three CRs (25%), four PRs (33.3%), and
      five NCs (41.6%). The 2-year survival rate of all patients was 51.9%, and MST was
      28.9 months. The 2-year survival rates of the M1 and A3 patients were 60.0% and
      41.7%, respectively. CONCLUSION: This study revealed that the present
      chemotherapy regimen is ineffective in treating metastatic lymph node lesions.
      Therefore, it will be necessary to evaluate the effectiveness of
      chemoradiotherapeutic agents from the perspective of their effects on metastatic
      lymph nodes.

PMID- 10888040
TI  - Role of mitochondrial DNA in radiation exposure.
AB  - PURPOSE: To evaluate the role of mitochondrial DNA (mtDNA) following exposure to
      ionizing irradiation. MATERIALS AND METHODS: We examined two human osteosarcoma
      cell lines either lacking mtDNA (143B.rho(0)206; rho0 cells) or having normal
      mtDNA (143B.TK-; rho+ cells). Cell survival curves were generated by using colony
      formation and micronucleus assay. The delay in population doubling time after
      irradiation was evaluated with dye exclusion tests. RESULTS: No significant
      difference was seen between rho+ and rho0 cell lines in colony formation assay.
      In micronucleus assay, rho0 cells showed a significantly lower rate of
      micronucleus formation. The ratios of binucleated cells with micronuclei were
      0.49 for rho+ cells and 0.25 for rho0 cells (p=0.005). In the dye exclusion test,
      rho0 cells revealed a delay of about 1.6 times in population doubling time
      compared with the control after 5 Gy of irradiation, similar to the 1.7 times of
      rho+ cells. CONCLUSION: In the human osteosarcoma cell line 143B.TK-, mtDNA does
      not influence clonogenic survival and delay of population doubling time after
      irradiation. However, the difference in micronucleus formation shows that mtDNA
      influences DNA damage after radiation exposure.

PMID- 10888041
TI  - Split-course radiotherapy with or without concurrent or sequential chemotherapy
      in non-small cell lung cancer.
AB  - In our department we designed a three-armed study to compare the effects of
      sequential and concurrent chemoradiotherapy in locally advanced non-small cell
      lung cancer. Each treatment arm consisted of 15 patients with histologically
      confirmed stage III non-small cell lung cancer. In group 1, the main treatment
      approach was split-course radiotherapy alone. In group 2, 6 mg/m2 of cisplatin
      was applied daily and concurrently with split-course radiotherapy. In group 3,
      two cycles of etoposide, ifosfamide, and cisplatin chemotherapy, which ended
      three weeks before split-course radiotherapy, was applied. Overall response rates
      were 40%, 66%, and 53% in groups 1, 2, and 3, respectively. Median survival was
      10, 11, and 10 months for groups 1, 2, and 3 respectively. Results are discussed
      in the light of the literature.

PMID- 10888042
TI  - The value of fast and ultrafast T2-weighted MR imaging sequences in hepatic
      enhancement with ferumoxides: comparison with conventional spin-echo sequence.
AB  - PURPOSE: The efficacy of superparamagnetic iron oxide (SPIO) was evaluated with
      fast T2-weighted imaging sequences such as turbo spin-echo (TSE), half-Fourier
      single shot turbo spin echo (HASTE), and echo-planar imaging (EPI) in comparison
      with the conventional spin-echo (SE) sequence on a 1.5 Tesla MR unit. MATERIALS
      AND METHODS: In a phantom study, we prepared vials containing different
      concentrations of ferumoxides (0, 0.25, 0.5, 0.75, and 1 micromol Fe) in 2%
      agarose simulating the liver. In an animal study, contrast medium in doses of 10,
      20, and 30 micromol/kg of ferumoxides was injected into the ear vein of rabbits
      weighing 3.0-4.0 kg under general anesthesia. MR imaging of the phantom and liver
      of the rabbits was obtained with the T2-weighted SE sequence (TR/TE=2000/20, 80),
      TSE sequences (TR/effective TE=2000/90, echo train length=7), HASTE (effective
      TE=64, 90 msec), and EPI (effective TE=64, 90 msec). Three rabbits in each group
      were imaged before and 1 hour after ferumoxides administration for in-vivo study.
      The Signal intensity of pre- and postcontrast imaging of the phantom or rabbits'
      livers was measured with operator-defined regions of interest, and signal-to
      noise ratios (SNR) were obtained. Immediately after imaging, the rabbits were
      sacrificed and the livers were removed at autopsy, followed by ex-vivo study. In
      a clinical study, 10 micromol/kg of ferumoxides was given in 34 consecutive
      patients with 31 solid tumors. The liver SNR were evaluated for all 34 patients,
      and tumor to-liver contrast-to-noise ratios (CNR) were evaluated for all 31 solid
      lesions. The same series of imaging techniques as in the experimental studies was
      performed for quantitative and qualitative analyses. RESULTS: In both in-vitro
      and in-vivo studies, SNR of the phantom or rabbits' livers significantly
      decreased after ferumoxides administration. The decrease in SNR on excised
      rabbits' livers was 72% for EPI, 36% for HASTE, 61% for SE, and 51% for TSE at a
      dose of 10 micromol/kg of ferumoxides. In the clinical study, HASTE and TSE
      showed significant improvement in CNRs after ferumoxides administration (p<0.05).
      Visual analysis revealed improvement in tumor detection for all sequences. On
      EPI, although contrast was excellent, severe image distortion was seen. Although
      the signal decrease with HASTE and TSE was somewhat inferior to those with EPI
      and SE, respectively, the effect of contrast enhancement on HASTE and TSE was
      marked on visual analysis. CONCLUSION: Although TSE sequences and HASTE sequences
      are less susceptible to magnetic field inhomogeneities than SE and EPI sequences,
      the decrease in liver signal on HASTE and TSE sequences was comparable to that on
      EPI and SE sequences, respectively. These sequences are useful clinically for
      ferumoxides imaging, because they are less sensitive to motion artifacts.

PMID- 10888043
TI  - Quality assurance for an image-guided frameless radiosurgery system using
      radiochromic film.
AB  - PURPOSE: The CyberKnife, a new type of machine for stereotactic irradiation, is
      composed of a combination of a robot (manipulator) and a linear accelerator; We
      measured the total pointing error of the therapy beam, aiming at improvement in
      the accuracy of the CyberKnife. METHODS AND MATERIALS: The CyberKnife keeps a
      number of coordinate systems such as the patient's coordinates, robotic
      coordinates, and IPS (image processing system) coordinates. Precise irradiation
      is possible if these coordinate systems are matched accurately. We always
      calculate the overall irradiation error using GAF MD-55 radiochromic film before
      irradiation treatment of the patient, and we have attempted to improve the
      accuracy of irradiation with the CyberKnife by feeding back the errors. RESULTS:
      The median of the error immediately after introducing the CyberKnife was 1.2 mm,
      and as a result of correction, we succeeded in reducing the error to 0.7 mm
      (median). Total pointing error after correction was significantly lower than that
      before correction (p=0.0023). CONCLUSIONS: This approach allowed us to reduce
      errors and establish a method for providing patients with highly accurate
      stereotactic irradiation. We believe these results endorse the validity of the
      method presented in this paper.

PMID- 10888044
TI  - Oddi sphincter and common channel: evaluation with pharmacodynamic MR
      cholangiopancreatography using fatty meal and secretin stimulation.
AB  - PURPOSE: This study was performed to assess the usefulness of pharmacodynamic MR
      cholangiopancreatography (MRCP) in depicting the segment covered by the Oddi
      sphincter. MATERIALS AND METHODS: Twelve volunteers were studied by
      pharmacodynamic MRCP. After stimulation by the oral intake of a fatty meal and an
      intravenous injection of secretin, a single-shot rapid acquisition relaxation
      enhancement (RARE) sequence was used to obtain consecutive images of the segment
      covered by the Oddi sphincter. The contraction range of the Oddi sphincter and
      the lengths of the common channel were measured on the MR console by comparing
      the most contracted image of the sphincter with the most relaxed image. RESULTS:
      Pharmacodynamic MRCP showed periodic contraction of the Oddi sphincter in all
      cases. The range of sphincteric contraction over the biliary duct was 8-19 mm
      (11.8+/-3.2 mm, mean +/- standard deviation) and over the pancreatic duct 8-23 mm
      (10.0+/-1.5 mm). In 11 of the 12 cases, the common channel was depicted and its
      length ranged from 3-8 mm (5.2+/-1.3 mm). CONCLUSION: Pharmacodynamic MRCP
      clearly depicted the range of contraction of the Oddi sphincter and the common
      channel, which are not usually revealed by conventional MRCP.

PMID- 10888045
TI  - Comparison of MR imaging and urodynamic findings in benign prostatic hyperplasia.
AB  - OBJECTIVE: In benign prostatic hyperplasia (BPH), it is uncertain whether the
      size of the prostate is related to the degree of urodynamically demonstrated
      bladder outlet obstruction. We compared MR imaging findings and urodynamic data
      in patients with surgically confirmed BPH. MATERIALS AND METHODS: We
      prospectively studied 43 benign prostatic hyperplasia (BPH) patients in whom
      transurethral resection of the prostate (TURP) was planned. We obtained T1- and
      T2-weighted images in the transverse and sagittal planes with a 1.5 Tesla
      superconducting unit. The predicted volume of the inner gland and the peripheral
      zone were obtained on T2-weighted transverse images. Prostatic protrusion into
      the urinary bladder (IB protrusion) and the inner gland ratio (IG ratio: inner
      gland volume/total prostatic volume) were determined. RESULTS: IB protrusion and
      inner IG ratio were significantly greater in patients with severe stenosis than
      in those without. A surgical capsule (SC) was seen in 20 of 25 patients (80%)
      with severe stenosis and 8 of 18 (44%) of those without it. The accuracy of IB
      protrusion + IG ratio, IB protrusion + surgical capsule, and IB protrusion + IG
      ratio + surgical capsule was 89%, and that of IG ratio + surgical capsule was
      86%. CONCLUSION: The inner gland ratio, protrusion into the bladder, and presence
      of surgical capsule were the most important factors in bladder outlet
      obstruction. The probability of outlet stenosis increases in patients with more
      than two of these criteria.

PMID- 10888046
TI  - Macrodystrophia lipomatosa: CT and MR findings.
AB  - Macrodystrophia lipomatosa is a congenital macrodactyly characterized by
      proliferation of all mesenchymal components, particularly fibroadipose tissue. We
      report imaging features of two such patients. MR imaging and CT scanning
      demonstrated proliferation of fatty tissue in the territory of the median nerve
      in the hands and forearms, characteristic of macrodystrophia lipomatosa.

PMID- 10888047
TI  - Application of self-expanding metallic stents to malignant stricture following
      mechanically stapled esophagojejunostomy: report of two cases.
AB  - Several types of self-expanding metallic stents (SEMS) were placed in two
      patients suffering from severe malignant stricture at the site of a mechanically
      stapled esophagojejunostomy used for the treatment of recurrent gastric cancer.
      Following modified Gianturco stent placement with limited success in one of the
      patients, an additional Ultraflex stent (Boston Scientific Co., Boston, USA)
      failed to expand satisfactorily at the outlet of the second stent. In the other
      patient, since the proximal end of an additional covered Ultraflex stent (Boston
      Scientific Co.) inserted through the first one failed to expand satisfactorily at
      the level of severe stenosis because of the extreme rigidity caused by the
      mechanical staples, a spiral Z-stent was inserted to dilate it. The cases
      reported here raise some problems associated with the treatment of severely
      malignant stricture accompanied by extreme rigidity following mechanically
      stapled esophagojejunostomy with SEMS.

PMID- 10888048
TI  - Cystic hamartoma of the renal pelvis: imaging features.
AB  - We report a case of a 50-year-old woman with histologically proven cystic
      hamartoma of the renal pelvis, focusing on the imaging findings and pathologic
      features. A large multicystic tumor with solid components in the left kidney was
      enhanced on both contrast-enhanced CT and gadolinium-enhanced MR images.
      Angiographic images showed irregular tumor vessels with moderate tumor stain.

PMID- 10888049
TI  - MR sialographic evaluation of sialectasia of Stensen's duct: comparison with X
      ray sialography and ultrasonography.
AB  - We describe a patient with unilateral sialectasia of Stensen's duct. X-ray
      sialography, MR sialography, and ultrasonography showed multiple stenoses and
      rosary dilatation of Stensen's duct during stimulation of the parotid gland.
      Before stimulation, Stensen's duct showed focal dilatation as indicated by MR
      sialography and ultrasonography. The patient also had ipsilateral masseter
      hypertrophy (BMH), which may be a cause of sialectasia.

PMID- 10888050
TI  - Pancreatic pseudoaneurysm converted from pseudocyst: transcatheter embolization
      and serial CT assessment.
AB  - We present a case of pancreatic pseudoaneurysm converted from a pseudocyst.
      Contrast-enhanced CT disclosed a round enhancing lesion at the previously
      identified pseudocyst, and angiography confirmed the diagnosis of a
      pseudoaneurysm. The pseudoaneurysm was successfully treated by arterial
      embolization. We believe arterial embolization to be the treatment of choice for
      pseudoaneurysm as a complication of pancreatitis.

PMID- 10888051
TI  - The relationship between posttraumatic stress symptomatology and suicidal
      behavior in school-based adolescents.
AB  - This study investigated the relationship between posttraumatic stress disorder
      (PTSD) symptomatology and suicidal behavior, specifically suicidal ideation and
      suicide attempt history, while controlling for depression and gender in 106
      adolescents in an urban high school. Participants completed self-report measures
      of the Adolescent Psychopathology Scales-Posttraumatic Stress Disorder Subscale
      (APS-PTS), the APS-Suicide Attempt History (APS-SAH), the Suicidal Ideation
      Questionnaire-Junior (SIQ-JR), and the Reynolds Adolescent Depression Scale
      (RADS). Analyses were conducted using a hierarchical multiple regression design
      to account for the relationship between PTSD symptomatology and depression.
      Regression results showed that after controlling for depression and gender, PTSD
      symptomatology was significantly related to suicidal ideation and showed a trend
      toward suicide attempt history. In addition, adolescents with high levels of PTSD
      symptomatology were more likely than peers with "average" levels of PTSD
      symptomatology to be currently thinking about suicide and to have made a past
      suicide attempt. These findings show that PTSD symptomatology has a unique
      relationship to adolescent suicidal behavior that cannot be explained by
      depression or gender. The importance of these results and their implications for
      future research are discussed.

PMID- 10888052
TI  - Predictors and correlates of bereavement in suicide support group participants.
AB  - A sample of 210 survivors of suicide, all participants in suicide support groups,
      was studied. Associations between demographic factors, circumstances surrounding
      the suicide, and overall levels of grief (using the Grief Experience
      Questionnaire) were calculated. Results showed that seeing the body at the scene
      of the death was the most significant predictor of high levels of distress, and
      support from family and friends was the strongest protective factor. Time since
      the death (for women) and attendance at Alcoholics Anonymous meetings (for those
      participating in nonsuicide support groups) were also significantly related to
      level of grief. For men, a moderate level of participation in other support
      groups, as compared with none, was associated with higher levels of grief. All
      other variables were not significant. Results suggest that a model that combines
      posttraumatic reactions and grief is most appropriate for the aftermath of
      suicide.

PMID- 10888053
TI  - Acculturative stress, depression, and suicidal ideation among Central American
      immigrants.
AB  - No previous studies have examined suicide risk among Central American immigrants.
      The present study explored the relationship between acculturative stress,
      depression, and suicidal ideation among Central American immigrants. Also
      examined were variables that predict depression and suicidal ideation. Elevated
      levels of acculturative stress were significantly correlated with high levels of
      depression and suicidal ideation. Family dysfunction, ineffective social support,
      nonpositive expectations concerning the future, low levels of religiosity, low
      levels of education and income, and lack of agreement with the decision to
      immigrate were significantly associated with high levels of depression and
      suicidal ideation. The overall findings suggest that Central American immigrants
      who experience elevated levels of acculturative stress may be at risk for
      experiencing heightened levels of depression and suicidal ideation. The findings
      highlight the importance of using culturally relevant clinical methods when
      assessing and treating depressed and potentially suicidal acculturating
      individuals.

PMID- 10888054
TI  - Cognitive distortions in the poetry of Anne Sexton.
AB  - Cognitive therapists have described cognitive distortions that are frequently
      associated with depression. These distortions include arbitrary inference,
      selective abstraction, overgeneralization, magnification and minimization,
      personalization, and dichotomous thinking, which are often present in suicidal
      individuals. This article suggests it is useful to conceptualize cognitive
      distortions in literary terms and uses the professional oeuvre of confessional
      poet Anne Sexton to identify salient examples.

PMID- 10888055
TI  - Suicide: a 15-year review of the sociological literature. Part I: cultural and
      economic factors.
AB  - Cultural and economic patterns from 130 sociological works on suicide from 1981
      to 1995 are reviewed in this article. The traditional Durkheimian perspective on
      suicide was often questioned by research on the impact of the mass media,
      alcohol, class, modernization, religion, and politics. Major theoretical
      developments included the application of differential identification theory to
      Phillips's model of copycat suicide, the application of criminology's opportunity
      theory to suicide, and new explanations for the link between alcohol and the
      social suicide rate. Explanations are reviewed for the major new suicide trend:
      after half a century of convergence, male and female suicide rates are diverging.
      Finally, the review notes patterns of continued stability in suicide research
      findings in areas such as racial differences and economic strain.

PMID- 10888056
TI  - Suicide: a 15-year review of the sociological literature. Part II: modernization
      and social integration perspectives.
AB  - This article reviews the findings of 84 sociological studies published over a 15
      year period. These studies deal with tests of the modernization and/or social
      integration perspectives on suicide. Research on modernization, religious
      integration, and political integration often questioned or reformulated the
      traditional Durkheimian perspective. A major new theoretical development,
      Pescosolido's religious networks perspective, gained some empirical support in
      the 15-year period. The strongest support for social integration theory came from
      research on marital integration, wherein more than three quarters of the research
      found a significant relationship. Finally, further research on migration, a force
      lowering social integration, continued to tend to find a positive link to
      suicide.

PMID- 10888057
TI  - Suicidal ideation in the United States.

PMID- 10888058
TI  - Reasons for living versus reasons for dying.

PMID- 10888059
TI  - Reasons for living versus reasons for dying.

PMID- 10888060
TI  - The expression of an alcohol deprivation effect in the high-alcohol-drinking
      replicate rat lines is dependent on repeated deprivations.
AB  - BACKGROUND: The alcohol deprivation effect (ADE) is a temporary increase in the
      ratio of alcohol/total fluid intake and voluntary intake of ethanol (EtOH)
      solutions over baseline drinking conditions when EtOH access is reinstated after
      a period of alcohol deprivation. The ADE has been posited to be an animal model
      for alcohol craving. In the current study, we examined the effects of initial
      deprivation length and number of deprivation exposures on the ADE in the
      replicate lines of the high-alcohol-drinking (HAD) rats. METHODS: Adult male HAD
      1 and HAD-2 rats received 24 hr free-choice access to 10% (v/v) EtOH and water
      for 6 weeks. Rats were then assigned to groups deprived of EtOH for 0 (control),
      or 2 to 8 weeks. All deprived groups were then given 24 hr access to EtOH for 2
      weeks before being deprived of EtOH for another 2 weeks. This cycle of 2 weeks of
      access and 2 weeks of deprivation was carried out for a total of four
      deprivations. RESULTS: After the initial EtOH deprivation period, EtOH
      consumption in HAD-1 and HAD-2 rats returned to baseline levels but failed to
      exhibit either an early onset ADE (initial 2 hr) or prolonged ADE (24 hr). An ADE
      was observed in two of the four deprived groups for the HAD-1 rats (2 week and 6
      week groups) and in all deprived groups for the HAD-2 rats after a second
      deprivation, and in all deprived groups of both lines after a third deprivation.
      In the HAD-2 line, but not in the HAD-1 line, the duration of the ADE was
      prolonged into the second reinstatement day after the fourth deprivation.
      CONCLUSIONS: The expression of an ADE was observed only after repeated
      deprivation periods in the HAD lines. The duration of the ADE was prolonged in
      the HAD-2 line, but not in the HAD-1 line, with repeated deprivations, which
      suggests a dissociation between selection for alcohol preference and the effects
      of repeated deprivations on the duration of the ADE.

PMID- 10888061
TI  - Ethanol-induced up-regulation of candidate plasminogen receptor annexin II in
      cultured human endothelial cells.
AB  - INTRODUCTION: Epidemiological studies indicate that moderate alcohol consumption
      reduces the risk for coronary heart disease and that this cardioprotective
      benefit may be mediated, in part, by increased fibrinolysis. Endothelial cells
      (ECs) synthesize plasminogen activators, tissue-type plasminogen activator (t
      PA), urokinase-type plasminogen activator (u-PA), receptors for plasminogen
      activators, and a receptor for plasminogen, annexin II (Ann-II). These receptors
      localize and facilitate receptor-bound plasminogen activator-mediated conversion
      of receptor-bound plasminogen to receptor-bound plasmin on the EC surface, which
      results in the regulated expression of surface-localized EC fibrinolytic
      activity. Ethanol is a systemic factor that affects these components, which
      increases EC fibrinolysis and hence reduces the risk for thrombosis, coronary
      heart disease, and myocardial infarction (MI). METHODS: This study was carried
      out to determine whether low ethanol (0.1% v/v) increased plasminogen receptor,
      Ann-II antigen (western blot), messenger ribonucleic acid (mRNA) (reverse
      transcription polymerase chain reaction; RT-PCR) expression, activity (ligand
      binding/Scatchard analysis), and hence fibrinolysis (plasmin generation) in
      cultured human ECs. RESULTS: Plasminogen receptor activity increased
      approximately 2-fold (2.5 vs. 5.6 x 10(6) sites/cell), as evidenced by increased
      125I-labeled Glu-plasminogen ligand binding/Scatchard analysis. In addition,
      western blot analyses indicated an increase in Ann-II antigen, and mRNA levels
      increased approximately 2-fold (RT-PCR). This increase in Ann-II expression was
      concomitant with approximately 2- to 3-fold sustained increase (approximately 24
      hr) in surface-localized EC fibrinolytic activity. Nuclear transcription run-on
      assays showed an approximately 5- to 6-fold increase in new 32P-labeled Ann-II
      mRNA levels, compared with controls (no ethanol). CONCLUSIONS: These results
      demonstrated that low ethanol increased Ann-II antigen/mRNA levels and up
      regulated Ann-II gene expression at the transcriptional level. The results
      further identify and define the contribution and role of the plasminogen
      receptor, Ann-II, in the ethanol-induced mechanism of increased EC fibrinolysis
      that may underlie and contribute, in part, to the cardioprotective benefit
      associated with moderate alcohol consumption.

PMID- 10888062
TI  - An abundant proneurotensin polymorphism, 479A>G, and a test of its association
      with alcohol dependence in a Finnish population.
AB  - BACKGROUND: Neurotensin is a 13-amino acid neuropeptide that endogenously
      modulates dopamine release in the central nervous system. In substance
      dependence, the mesolimbic dopamine system has been postulated to be a central
      structure that mediates rewarding and reinforcing effects. Neurotensin receptors
      in the neurons of the ventral tegmental area facilitate dopamine release, making
      the neurotensin gene an excellent candidate gene for alcohol dependence and for
      other behaviors that involve reinforcement. METHODS: A total of 639
      psychiatrically interviewed Finns were genotyped for proneurotensin 479A>G
      polymorphism. We used the polymorphism as a marker to study the association
      between proneurotensin gene and alcohol dependence by comparing 229 unrelated
      Finnish healthy controls to 134 unrelated alcohol-dependent (DSM-III-R criteria)
      subjects who were also criminal offenders. In addition, 276 relatives of the
      alcohol-dependent and control subjects were genotyped. RESULTS: The frequencies
      of the genotypes in the whole sample (n = 639) were 0.84 for 479A/A, 0.16 for
      479A/G, and 0.003 for 479G/G. The frequency of the rarer 479G allele was 0.07 and
      0.06 in controls and alcohol-dependent subjects, respectively, and this
      difference was not statistically significant (chi2 = 0.264, df = 1, p = 0.61,
      controls vs. alcohol-dependent subjects). CONCLUSIONS: The results of the
      comparison between psychiatrically interviewed controls and alcoholics from a
      relatively well defined population indicate that the proneurotensin 479A>G
      polymorphism is not strongly associated with alcohol dependence. The results do
      not rule out a role for this gene in the pathogenesis of alcoholism or in
      differential vulnerability.

PMID- 10888063
TI  - A new assessment of the ability of oral ethanol to function as a reinforcing
      stimulus.
AB  - BACKGROUND: In animal studies, the ability of ethanol to function as a reinforcer
      has been described as weak to moderate. This is in contrast with the human
      condition, where the consumption of alcoholic beverages can result in a variety
      of unwanted drinking behaviors. However, when the ethanol self-administration
      pattern is examined, animal studies over the last several years indicate that the
      ability of ethanol presentation to maintain behavior may be greater than
      originally assumed. METHODS: We reevaluated the ability of ethanol to function as
      a reinforcing stimulus in two paradigms by using an analysis of drinking bout
      characteristics. Data from previous studies that employed two self-administration
      models were analyzed. With the "dipper" model, small amounts of ethanol are
      presented after each completion of a response requirement; with the "sipper"
      model, the animal is allowed access to a drinking tube that contains ethanol for
      an extended period after completing a single response requirement. For both
      models, the consumption pattern could be characterized as occurring in a bout.
      Each drinking bout was divided into runs within the bout, and run rates and size
      were analyzed. As well, in the sipper model, the data on response requirement
      size were reviewed to demonstrate the ability of ethanol presentation to maintain
      high levels of responding in this model. RESULTS: From this assessment, we
      suggest that ethanol presentation in non-food- or non-water-restricted rats is as
      reinforcing as many other stimuli generally considered to be strong reinforcers
      (i.e., food in food-restricted rats). Using run size, we demonstrated that intake
      control appears to be regulated by shifts in run size during the bout and not run
      rate. CONCLUSIONS: Assessment of the pattern of ethanol consummatory bouts and
      the behaviors that precede them is critical in understanding how ethanol
      functions as a reinforcer. By using a drinking pattern analysis, the shifts in
      the momentary salience of the ethanol stimulus can be evaluated in these animal
      models. In addition, the separation of responding required to gain access to
      ethanol from consumption of ethanol demonstrated that ethanol presentation in
      this procedure can be a strong reinforcer for rats.

PMID- 10888064
TI  - Season of birth and substance abuse: findings from a large national sample.
AB  - BACKGROUND: Season of birth is a putative etiological factor for several
      psychiatric illnesses. An excess of late winter and early spring births has been
      demonstrated repeatedly for schizophrenia, which has usually been interpreted as
      the result of prenatal or infant exposure to seasonally mediated "harmful
      effects," such as infectious diseases. This study determined whether the seasonal
      birth rates of substance abusers differed from those of unaffected control
      groups. METHODS: The 1992 National Longitudinal Alcohol Epidemiologic Survey, an
      interview-based study of 42,862 men and women, provided data to assess the
      association between quarter year of birth and lifetime diagnoses of substance
      abuse. RESULTS: Logistic regression revealed decreases in winter births in men
      with histories of alcohol dependence. The significant interaction of sex with
      season of birth reflected an excess of fall births among male but not female
      alcoholics. In contrast, there was no evidence of seasonality of birth among
      alcohol abusers. Men and women with histories of illicit drug use had excesses of
      fall birth. DISCUSSION: Birth rates of men with past or present alcohol
      dependence, and of men and women with histories of illicit drug use, implicated
      seasonal factors in the pathogenesis of substance abuse. The similar birth
      patterns of illicit drug users and male alcoholics suggest that they may share
      some common etiological factor, such as seasonal effects on environmental
      temperature, hormonal function, or susceptibility to viral infection during
      pregnancy or early infancy.

PMID- 10888065
TI  - Dissociation between the time course of ethanol and extracellular dopamine
      concentrations in the nucleus accumbens after a single intraperitoneal injection.
AB  - BACKGROUND: Dopamine release in the nucleus accumbens has been linked to the
      reinforcing effects of ethanol, but the time course or relationship of this
      response to ethanol concentrations in the brain has not been studied. METHODS:
      Various doses of ethanol (0-2.0 g/kg) were administered intraperitoneally to male
      Sprague Dawley rats, and dopamine and ethanol were simultaneously analyzed in
      dialysate samples from the nucleus accumbens. A separate study to compare the
      ethanol-induced dopamine response in male and female rats was carried out by
      using a 1 g/kg intraperitoneal dose of ethanol. RESULTS: In male rats, 1 and 2
      g/kg ethanol significantly increased dialysate dopamine by 40% over basal,
      whereas 0.25 and 0.5 g/kg ethanol produced a nonsignificant 20% increase.
      Dialysate ethanol concentrations exhibited a curvilinear decline after reaching
      peak levels for the lower doses but showed a linear decrease after 1 and 2 g/kg.
      There was a dissociation between the time courses of extracellular dopamine and
      ethanol after 1 and 2 g/kg ethanol treatment. The dopamine response returned to
      basal within 90 min, whereas the ethanol concentrations remained elevated. In a
      separate study that compared male and female rats, the ratio of the dopamine
      response over basal to the dialysate ethanol concentrations was significantly
      decreased at 60 min after an injection of 1 g/kg. However, there were no
      differences between males and females. CONCLUSIONS: The dissociation between
      dopamine and ethanol levels may reflect the development of acute tolerance to
      ethanol-induced dopamine release in the nucleus accumbens within the time course
      of a single acute injection. Given the strong links between dopamine and ethanol
      reinforcement, our findings may be relevant for understanding the time course of
      ethanol's reinforcing effects in vivo.

PMID- 10888066
TI  - Subjective and objective responses to ethanol in moderate/heavy and light social
      drinkers.
AB  - BACKGROUND: Individuals who drink heavily are at an increased risk for adverse
      consequences of drinking and progression of their drinking habits to abuse or
      dependence. Therefore, it is important to delineate factors associated with their
      heavy drinking. METHODS: We examined individual differences in subjective and
      objective responses to ethanol associated with level of consumption by
      reanalyzing data from the nine heaviest and nine lightest social drinkers from
      each of two independently collected subject samples: Holdstock and de Wit (1998)
      and King et al. (1997). The light drinkers in both samples consumed five or less
      alcoholic drinks per week, whereas the moderate/heavy drinkers consumed eight or
      more drinks per week with frequent binge episodes. Acute subjective and objective
      responses to ethanol (0.6 or 0.8 g/kg) or placebo were compared in the two groups
      at baseline and during rising and falling blood alcohol concentrations. RESULTS:
      Moderate/heavy drinkers reported greater stimulant-like and fewer sedative-like
      and aversive subjective effects after ethanol than did lighter drinkers. These
      differences occurred in the absence of any group differences in breath alcohol
      levels, performance effects, or neuroendocrine changes or in overall reports of
      feeling any drug effects. CONCLUSIONS: These data indicate that habitual
      moderate/heavy ethanol use was associated with greater stimulant-like effects
      after an acute dose of alcohol. This finding is consistent with the idea (Newlin
      and Thomson, 1990, 1999) that individuals who experience greater stimulant-like
      effects during the ascending limb and lesser sedative-like effects on the
      descending limb of the blood alcohol concentration curve may be at greater risk
      for developing ethanol use disorders. Although we cannot determine the causality
      of this association, sensitivity to the stimulant effects of ethanol may play an
      important role in the continuation of heavy ethanol use and the increased risk of
      negative consequences from this use.

PMID- 10888067
TI  - Reverse microdialysis of a dopamine uptake inhibitor in the nucleus accumbens of
      alcohol-preferring rats: effects on dialysate dopamine levels and ethanol intake.
AB  - BACKGROUND: The mesolimbic dopamine (DA) system has been implicated in mediating
      the reinforcing actions of ethanol (EtOH). This study examines the effects of
      local perfusion of the DA uptake inhibitor GBR12909 (GBR) on (1) DA levels in the
      nucleus accumbens (NAc) and (2) EtOH drinking in alcohol-preferring rats.
      METHODS: Stable drinking of a 15% (v/v) EtOH solution (minimum of 0.75 g/kg body
      weight) was established in daily 1 hr limited access sessions. Rats were then
      implanted with bilateral guide cannulae aimed 4 mm above the NAc. After recovery
      from surgery, concentric microdialysis probes (2 mm dialysis membrane surface)
      were inserted into the NAc. Most placements were in the shell or overlapping both
      shell and core. Two days later, the probes were perfused at 1.0 microl/min with
      artificial cerebral spinal fluid (aCSF) for at least a 90 min washout period
      followed by collection of five basal samples over 150 min. Rats were then
      perfused with either aCSF alone or 10, 25, 100, or 200 microM of GBR for 240 min
      on the first day of microdialysis. During the last 60 min of the drug treatment
      phase, rats were given their scheduled access to 15% EtOH. All rats were then
      perfused with aCSF for the last 90 min of the experiment. The following day, the
      procedure was repeated, but animals that received aCSF on the first day were
      given a dose of GBR and rats given GBR on the first day received only aCSF.
      RESULTS: GBR perfusion increased extracellular NAc DA levels dose dependently to
      more than 800% of basal levels at 100 to 200 microM but failed to alter EtOH
      intake (p > 0.05, paired t test) at any concentration tested. Moreover, after 100
      microM of GBR perfusion had terminated, the extracellular levels of DA in the NAc
      remained elevated for approximately 24 hr (790% of day 1 basal; p < 0.05). The
      increase in dialysate DA levels observed during GBR perfusion with 100 microM was
      significantly greater for EtOH-experienced rats than for EtOH-naive rats [F(7,59)
      = 14.85, p < 0.0001, analysis of variance, Student-Newman-Keuls post hoc test].
      CONCLUSIONS: The results suggest (1) that EtOH drinking experience induces
      neuroadaptations that increase DA release in the NAc, and (2) that additional
      elevation in synaptic levels of DA in the NAc does not influence the maintenance
      of ongoing alcohol drinking under scheduled access conditions in alcohol
      preferring animals.

PMID- 10888068
TI  - Ethanol-induced c-fos expression in catecholamine- and neuropeptide Y-producing
      neurons in rat brainstem.
AB  - BACKGROUND: Previous studies have used c-Fos-like immunoreactivity (cFLI) to
      examine the neuroanatomical location of cells that are activated in response to
      ethanol administration. However, the use of cFLI alone fails to reveal the
      phenotypical identity of cells. In the present study we used double-labeling
      procedures to identify the neurochemical phenotype of neurons that showed ethanol
      induced cFLI in the rat brainstem. METHODS: Individual groups of rats received
      intraperitoneal injection of ethanol (1.5 g/kg or 3.5 g/kg) or isotonic saline
      (23 ml/kg). To assess the specificity of cFLI induced by ethanol, we injected
      other rats with the drug lithium chloride (LiCl; 76 mg/kg). Two hours after
      injection, rats were killed and their brains were processed for
      immunohistochemistry. RESULTS: Both doses of ethanol promoted cFLI in several
      brainstem regions, including the nucleus of the solitary tract (NTS), the locus
      coeruleus (LC), and the ventrolateral medulla (VLM). Although LiCl caused
      significant cFLI in the NTS, this drug promoted only minimal cFLI in the VLM and
      no significant activation in the LC. We found that a significant proportion of
      tyrosine hydroxylase (TH)-positive neurons coexpressed ethanol-induced cFLI in
      the VLM (approximately 75-85%), the NTS (approximately 65-75%), and the LC
      (approximately 30-65%). Additionally, a significant proportion of neuropeptide Y
      (NPY)-producing neurons in the VLM coexpressed ethanol-induced cFLI
      (approximately 60-75%). On the other hand, LiCl promoted activation of TH
      positive neurons in the VLM and the NTS but failed to stimulate cFLI in TH
      producing neurons in the LC or in NPY-producing neurons of the VLM. CONCLUSIONS:
      Neurons in the rat brainstem that show ethanol-induced c-Fos expression produce
      catecholamines and NPY. This research demonstrates the usefulness of double
      labeling immunohistochemistry procedures for identifying the neurochemical
      identity of neurons that are activated after ethanol administration.

PMID- 10888069
TI  - Platelet adenylyl cyclase activity as a trait marker of alcohol dependence.
      WHO/ISBRA Collaborative Study Investigators. International Society for Biomedical
      Research on Alcoholism.
AB  - BACKGROUND: There is compelling evidence that genetic factors play a major role
      in the development of alcohol dependence. Platelet adenylyl cyclase (AC) activity
      has been proposed as a biochemical marker for differentiating alcohol-dependent
      and nondependent subjects, but the sensitivity and specificity of this marker
      have not been ascertained. The objective of this study was to determine the
      sensitivity and specificity of platelet AC activity in identifying alcohol
      dependent subjects and to ascertain the effect of medical/ psychiatric variables,
      drinking and smoking history, and age and body weight on AC activity. METHODS:
      The cross-sectional study was conducted from 1995 to 1998. Participants were 210
      Australian White men who were community volunteers and alcohol treatment
      inpatients in Sydney, Australia. There were 41 nondrinkers, 140 drinkers, and 29
      men who were entering alcohol treatment. The main outcome measure was platelet AC
      activity. Classification variables were plasma ethanol, gamma
      glutamyltransferase, aspartate aminotransferase, serum carbohydrate-deficient
      transferrin (CDT), and urinary 5-hydroxytryptophol/5-hydroxyindoleacetic acid (5
      HTOL/5-HIAA) levels, and World Health Organization/International Society for
      Biomedical Research on Alcoholism Interview Schedule variables, which included
      alcohol use and dependence criteria. RESULTS: Among subjects who reported
      abstinence for at least 4 days, both cesium fluoride (CsF)- and forskolin
      stimulated platelet AC activities were significantly lower in those with a
      lifetime history of alcohol dependence compared with those with no such history
      (p < 0.005 and p < 0.05, respectively). The sensitivity and specificity of CsF
      stimulated AC activity to discriminate individuals with a lifetime history of
      alcohol dependence were 75% and 79%, respectively. Similar values for sensitivity
      and specificity for CsF-stimulated AC activity were calculated when
      discriminating current alcohol dependence in the subjects in our sample.
      Irrespective of the history of alcohol dependence, persons who had consumed
      alcohol recently (within the last 3-4 days) showed significantly higher mean
      basal, CsF-stimulated, and forskolin-stimulated AC activity (p < 0.001), as did
      those who had elevated 5-HTOL/5-HIAA ratios or CDT levels, indicative of recent
      (heavy) drinking. The "normalization" of platelet AC activity to baseline levels
      after an individual stops drinking may be related to the generation of new
      platelets during the abstinence period. Conduct disorder and antisocial
      personality disorder were not associated with low AC activity, but low forskolin
      stimulated AC activity was associated with major depression. CONCLUSIONS: We
      found that CsF- and forskolin-stimulated platelet AC activity discriminates
      between subjects with and without alcohol dependence in a population of subjects
      who had not consumed significant quantities of ethanol recently. Recent alcohol
      consumption is a confounding variable that can alter the measured levels of AC
      activity. Forskolin-stimulated platelet AC activity also may be influenced by a
      history of major depression.

PMID- 10888070
TI  - Regional brain metabolism during alcohol intoxication.
AB  - BACKGROUND: Ethanol has a broad range of actions on many neurotransmitter
      systems. The depressant actions of ethanol in the brain are related in part to
      facilitation of gamma-aminobutyric acid (GABA) neurotransmission via its
      interaction with the benzodiazepine/GABA receptor complex. The purpose of this
      study was to evaluate the effects of ethanol on regional brain metabolism in 10
      healthy right-handed men. The results were compared with those we previously
      published in a different group of 16 normal male subjects who received
      intravenous lorazepam, a benzodiazepine drug that also enhances GABA
      neurotransmission. METHODS: The subjects were scanned with positron emission
      tomography and [F-18] fluorodeoxyglucose twice: 40 min after the end of placebo
      (diet soda) or ethanol (0.75 g/kg) oral administration. Image data sets were
      analyzed by using both the region of interest and the statistical parametric
      mapping (SPM) approach. SPM was used to generate a difference image between
      baseline and ethanol, which we compared to the difference image between baseline
      and lorazepam (30 microg/kg). RESULTS: Ethanol significantly increased self
      reports of "high" (p < or = 0.0001), dizziness (p < or = 0.004), and intoxication
      (p < or = 0.0001). Ethanol significantly decreased whole brain (-25 +/- 6%, p <
      or = 0.0001) and regional metabolism. Normalization of the regional measures by
      whole brain metabolism (relative measures) showed that ethanol decreased relative
      metabolic activity in occipital cortex (-4.9 +/- 4.1%, p < or = 0.006), whereas
      it increased relative metabolic act in left temporal cortex (+3.5 +/- 2.9%, p <
      or = 0.006) and left basal ganglia (+9 +/- 6.3%, p < or = 0.0009). SPM analyses
      revealed the same pattern of responses as the relative measures, showing
      decreases in occipital cortex and increases in left temporal cortex. Comparison
      of the relative measures and the SPM analyses obtained with lorazepam data
      revealed a similar pattern of effects, with relative decreases in occipital
      cortex (-7.8 +/- 4.8%) and relative increases in left temporal cortex (+3.8 +/-
      5.7%). Lorazepam, but not ethanol, also decreased thalamic metabolism (-11.2 +/-
      7.2%). CONCLUSIONS: These results support similar though not identical mechanisms
      for the effects of alcohol and benzodiazepines on brain glucose metabolism. The
      fact that lorazepam, but not alcohol, reduced thalamic metabolism, an effect
      associated with sleepiness, could explain the higher sedative effects of
      lorazepam than of alcohol.

PMID- 10888071
TI  - 4.0 T water proton T1 relaxation times in normal human brain and during acute
      ethanol intoxication.
AB  - BACKGROUND: It has been reported that acute ethanol intoxication decreases the
      brain water proton magnetic resonance T1 values, an effect that has been
      interpreted to indicate brain dehydration during this condition. Because water
      macromolecular interactions largely determine tissue water T1, another possible
      explanation for reduced brain water proton T1 values is that the interaction
      between water and brain macromolecules is altered by ethanol. METHODS: A 4.0 T
      magnetic resonance imaging (MRI) instrument was used to measure brain water
      proton T1 relaxation times before, during, and after ethanol intoxication (dose,
      0.75 mg/kg) in healthy controls. RESULTS: The T1 relaxation times as assessed
      with MRI were highly reproducible. The mean, paired ethanol-induced differences
      in T1 were -0.004 +/- 0.007 sec (mean +/- standard deviation) for white matter
      and 0.010 +/- 0.015 sec for internal gray matter structures, neither of which was
      significant. CONCLUSIONS: This reasonably sensitive measurement does not support
      the view that tissue water content or water macromolecule interactions are
      significantly altered in the brain during acute alcohol intoxication in otherwise
      healthy subjects.

PMID- 10888072
TI  - The modulation of B16BL6 melanoma metastasis is not directly mediated by
      cytolytic activity of natural killer cells in alcohol-consuming mice.
AB  - BACKGROUND: Previous studies in our laboratory indicate that alcohol consumption
      suppresses the metastasis of B16BL6 melanoma, whereas the cytolytic activity of
      natural killer (NK) cells is decreased in female C57BL/6 mice given 20% w/v
      alcohol in their drinking water. In the present study, we further evaluated the
      involvement of NK cells and alcohol consumption in the cytolytic activity of NK
      cells, the surface expression of NK phenotypic markers, and metastasis of B16BL6
      melanoma in C57BL/6 beige (bgJ/bgJ) mutant mice, which possess inherently low NK
      cell cytolytic activity. METHODS: Beige and control (bgJ/+) mice were given
      either water or 20% w/v of alcohol in drinking water for 6 1/2 to 7 weeks before
      assay for cytolytic activity, surface marker expression, and inoculation with
      B16BL6 melanoma intravenously or into the pinna of the ear. RESULTS: NK cytolytic
      activity was suppressed in beige mice, and alcohol consumption did not modulate
      further the cytolytic activity. Beige mice had a lower percentage of NK cells in
      the peripheral blood and spleen than control mice. Peripheral blood lymphocytes
      from beige mice also exhibited a reduced percentage of CD4+ T lymphocytes.
      Alcohol consumption similarly reduced the percentages of NK1.1- and LGL-1
      expressing lymphocytes in the peripheral blood and spleen and reduced the
      percentage of CD8+ T lymphocytes in the peripheral blood in both control and
      beige mice. Tumor lung colonization was increased in beige mice relative to
      control mice after intravenous inoculation of B16BL6 melanoma. The increase was
      more pronounced in water-drinking beige mice than in control mice irrespective of
      alcohol consumption. Tumor lung colonization was significantly decreased (p <
      0.05) by alcohol consumption in one experiment and partially decreased (p = 0.07)
      in the other. Mice that were inoculated into the pinna of the ear also exhibited
      a blunted antimetastatic response to alcohol consumption. CONCLUSIONS: These data
      suggest that the presence of the beige mutation diminishes the antimetastatic
      effect of alcohol consumption and that there is no interaction between alcohol
      consumption and NK-cell activity in the modulation of lung metastasis of B16BL6
      melanoma cells.

PMID- 10888073
TI  - Role of nitric oxide in endotoxin-induced hepatic microvascular dysfunction in
      rats chronically fed ethanol.
AB  - BACKGROUND: Nitric oxide (NO) appears to be involved in the pathogenesis of
      endotoxin-induced liver injury. However, little is known about how NO acts on the
      hepatic microcirculation, especially in alcohol-fed animals. We examined the
      roles of NO in endotoxin-induced hepatic microvascular dysfunction in control and
      ethanol-fed rats. METHODS: One lobe of the liver was observed with an intravital
      microscope. Flow velocity of fluorescein isothiocyanate-labeled erythrocytes in
      sinusoids was measured with an off-line velocimeter. Portal pressure and mean
      arterial pressure also were measured. RESULTS: After administration of endotoxin
      to control, the flow velocity decreased after 30 min. Portal pressure increased
      after 45 min. However, in ethanol-fed rats, both the flow velocity and portal
      pressure temporarily increased in the early phase. Thereafter, the flow velocity
      decreased and portal pressure increased. At 30 min after administration of the
      endotoxin, pretreatment with 10 mg/kg of an NO synthase inhibitor, NG-monomethyl
      L-arginine (L-NMMA), enhanced the endotoxin-induced decrease in the velocity of
      erythrocytes in the midzonal region of both control and ethanol-fed rats.
      Although 0.5 mg/kg of L-NMMA enhanced the endotoxin-induced reduction of
      erythrocyte velocity in the midzonal region of ethanol-fed rats, L-NMMA enhanced
      the endotoxin-induced reduction of erythrocyte velocity in the pericentral region
      of control rats. At 60 min after the endotoxin administration, L-NMMA did not
      affect the endotoxin-induced decrease of erythrocyte velocity in either control
      or ethanol-fed rats. Although 10 mg/kg of L-NMMA increased mean arterial pressure
      both in control and ethanol-fed rats, 0.5 mg/kg of L-NMMA did not change mean
      arterial pressure in either control or ethanol-fed rats. CONCLUSIONS: These
      results suggest that NO is involved in endotoxin-induced hepatic microvascular
      dysfunction, which may contribute to the sequential liver injury, especially in
      alcohol-fed animals.

PMID- 10888074
TI  - Effects of CH-100, a chinese herbal medicine, on acute concanavalin A-mediated
      hepatitis in control and alcohol-fed rats.
AB  - BACKGROUND: Administration of concanavalin A (Con A) leads to acute hepatitis
      that involves T-cell activation and inflammatory mediator production in mice and
      rats. We examined the role of CH-100, a Chinese herbal medicine previously
      trialed in human hepatitis C, in the prevention of Con A-related, T-cell
      mediated, acute liver injury in rats. METHODS: Female Wistar rats were fed 40%
      ethanol, 2% sucrose, or isocaloric sucrose for 8 weeks. At the same time, these
      animals were fed either the Chinese herbal medicine CH-100 (4 tablets/kg body
      weight/ day) or placebo in chow daily. Blood from the tail vein was collected for
      endotoxin (lipopolysaccharide) assay at 0, 4, and 8 weeks of ethanol consumption.
      Twenty-four hours after injection of Con A (20 mg/kg body weight) or phosphate
      buffered saline, blood from the tail vein was collected for alanine
      aminotransferase and tumor necrosis factor (TNF)-alpha assays. Liver-associated
      CD4+ T cells were isolated from liver perfusates and then cultured with Con A (5
      microg/ml) at 37 degrees C for 24 hr. Supernatants were harvested for TNF-alpha
      assay. The proportion of CD4+ T cells in blood and liver perfusates was measured.
      Liver samples were collected for histopathological analysis. RESULTS:
      Lipopolysaccharide levels were significantly reduced in CH-100-treated ethanol
      fed rats compared with placebo-treated rats. After Con A injection, alanine
      aminotransferase levels were lower at 12 and 24 hr in herb-treated rats compared
      with placebo-treated rats. Furthermore, serum TNF-alpha levels were lower in
      ethanol-fed rats on herbal treatment. A significant decrease in TNF-alpha
      production by liver-associated CD4+ T cells in culture was observed in CH-100
      treated ethanol-fed rats. CH-100 treatment was associated with a decreased
      percentage of CD4+ cells in both blood and liver perfusate in all groups. Herb
      treated rats displayed markedly less hepatic necrosis and a reduced CD4+ T-cell
      infiltrate in portal areas than did placebo-fed rats. CONCLUSIONS: The results
      demonstrate that CH-100 modified the T-cell response to Con A injection. The
      effect was more marked in ethanol-fed rats, which suggests a possible role for CH
      100 in treating alcoholic liver disease.

PMID- 10888075
TI  - Heart mitochondrial respiratory chain complexes are functionally unaffected in
      heavy ethanol drinkers without cardiomyopathy.
AB  - BACKGROUND: Harmful effects of chronic ethanol intake on liver mitochondria have
      been clearly demonstrated; however, mitochondria from skeletal muscle are
      preserved, and the effect of ethanol on heart mitochondria remains controversial.
      We assessed individual enzyme activity of mitochondrial respiratory chain (MRC)
      complexes and membrane oxidative damage of heart mitochondria in active ethanol
      drinkers before the development of dilated cardiomyopathy. PATIENTS AND METHODS:
      Heart samples were obtained from otherwise healthy organ donor individuals with a
      sudden death of traumatic or neurological cause in whom hearts could not be used
      because of absence of matched receptors or size inadequacy. Detailed history of
      alcohol intake was achieved from the relatives. Citrate synthase activity was
      spectrophotometrically assayed, as well as absolute (nmol x min(-1) x mg protein(
      1)) and relative (corrected by citrate synthase) activities of complex I, II,
      III, and IV of the MRC. Oxidative damage of myocardium membranes was assessed
      measuring the degree of lipid peroxidation by fluorescence using cis-parinaric
      acid as probe. RESULTS: We included 10 ethanol drinkers (age 53 +/- 13 years,
      100% males, mean lifetime intake of 15.6 +/- 7.9 kg ethanol kg body weight(-1))
      and 12 controls (age 60 +/- 10 years, 75% males). Mitochondrial content did not
      differ between the two groups. Absolute enzyme activities for ethanol drinkers
      and controls were, respectively, 145 +/- 75 and 130 +/- 50 for complex I (p =
      NS); 399 +/- 193 and 376 +/- 100 for complex II (p = NS); 719 +/- 288 and 714 +/-
      308 for complex III (p = NS); and 475 +/- 139 and 570 +/- 160 for complex IV (p =
      NS). After correcting such activities by citrate synthase activity, we failed
      again to demonstrate differences between ethanol drinkers and controls. Lipid
      peroxidation of myocardium membranes was similar in both groups. CONCLUSIONS:
      Chronic ethanol drinkers without cardiomyopathy exhibit normal MRC activity in
      the heart and do not show increased oxidative damage in myocardial membranes.

PMID- 10888076
TI  - Brain high energy phosphate responses to alcohol exposure in neonatal rats: an in
      vivo 31P-NMR study.
AB  - BACKGROUND: The mechanisms that mediate fetal brain injury which results from
      maternal alcohol consumption are not well understood. Although fetal hypoxia is a
      popularly proposed mechanism, it has been difficult to assess brain oxygenation
      in vivo. We measured intracellular high energy phosphate concentrations and
      estimated intracellular pH (pHi) in brains of unanesthetized neonatal rat pups by
      using in vivo 31P-NMR spectroscopy. We reasoned that decreases in brain
      oxygenation sufficient to result in brain injury would also reduce high energy
      phosphates and pHi. METHODS: On postnatal day 4, before alcohol administration,
      pups were placed into a 20 mm diameter NMR probe, their heads were positioned
      carefully in the center of the 31P detection coil, and spectra were collected
      over 20 min. Animals were then fed diet with or without 4.5 g/kg of ethanol in
      two (in succession) of 12 daily feedings via artificial rearing methods. A second
      spectrum was collected at 90 min after the beginning of the second alcohol
      feeding, at the time that coincided with the peak blood alcohol concentration
      (BAC). Identical feedings were performed daily until day 9, when pre- and
      postfeeding spectra were again obtained. Positive control groups were fed control
      diet and were studied in atmospheres of 5% oxygen, 95% nitrogen or 0% oxygen,
      100% nitrogen. RESULTS: Phosphocreatine (PCr), beta-adenosine triphosphate (ATP),
      and pHi decreased and inorganic phosphate (Pi) increased in day 4 animals
      subjected to 0% oxygen (20 min) compared with pretreatment and all other
      treatment groups. Day 9 animals did not tolerate these conditions. There were no
      significant changes in response to 5% oxygen on day 4, but Pi increased and beta
      ATP decreased compared with pretreatment values and compared with alcohol and
      control groups on day 9. There were no changes in PCr, beta-ATP, or pHi in
      response to alcohol treatment at either age. PCr was significantly increased in
      the alcohol and 5% oxygen groups and apparently increased in the control group on
      day 9 compared with day 4, most likely due to increases in cranial muscle mass
      within the NMR coil. CONCLUSIONS: We conclude that acute alcohol exposure that
      results in peak BACs of 315 mg/dl does not alter brain high energy phosphate
      concentrations or pHi in neonatal rat pups, although these BACs are known to
      result in significant brain injury. These findings do not support hypoxia as a
      mechanism of alcohol-mediated brain injury during the third trimester equivalent
      in the rat pup model.

PMID- 10888077
TI  - High salivary acetaldehyde after a moderate dose of alcohol in ALDH2-deficient
      subjects: strong evidence for the local carcinogenic action of acetaldehyde.
AB  - BACKGROUND: Due to a point mutation, aldehyde dehydrogenase-2 (ALDH2) isoenzyme
      is deficient in 30% to 50% of Asians. Among Asian ALDH2-deficient heavy drinkers,
      the risk for digestive tract cancers is markedly increased (odds ratio 3.4-54.2).
      The reason for this is unknown but could be due to the local carcinogenic action
      of acetaldehyde. METHODS: Salivary and blood acetaldehyde levels were determined
      in 20 healthy Asians after a moderate dose of alcohol (0.5 g/kg of body weight).
      Salivary acetaldehyde production capacity from ethanol in vitro was measured
      also. ALDH2 genotype of the Asians was determined from isolated leukocyte
      deoxyribonucleic acid by polymerase chain reaction/restriction fragment length
      polymorphism method. Acetaldehyde content of parotid gland saliva was measured in
      three ALDH2-deficient Asians and three White subjects with normal ALDH2 after the
      same dose of ethanol. RESULTS: Seven of the Asians were heterozygous for the
      mutant ALDH2*2 allele (flushers). They had two to three times higher salivary
      acetaldehyde levels than the Asians (n = 13) with normal ALDH2 throughout the
      follow-up period of 240 min (p < 0.001). Only in the flushers did the parotid
      gland contribute to salivary acetaldehyde production. The in vitro capacity of
      saliva to produce acetaldehyde from ethanol was equal in both groups. The
      flushers' blood acetaldehyde levels were only one ninth of the levels in saliva.
      CONCLUSIONS: By using this human "knockout model" for deficient acetaldehyde
      removal, we found that in addition to oral microflora, acetaldehyde in saliva may
      also originate from the oxidation of ethanol in the parotid gland. When combined
      with earlier epidemiological data, these results offer a strong evidence for the
      local carcinogenic action of acetaldehyde in humans.

PMID- 10888078
TI  - Integrating person-centered and variable-centered approaches in the study of
      developmental courses and transitions in alcohol use: introduction to the special
      section.
AB  - This special section consists of research from the symposium "Integrating Person
      Centered and Variable-Centered Approaches to the Study of Developmental Courses
      and Transitions in Alcohol Use," presented at the 1999 Annual Meeting of the
      Research Society on Alcoholism. The section focuses on ways to integrate variable
      centered and person-centered approaches to better understand longitudinal
      trajectories of alcohol use and associated problems. Our aim is to increase
      awareness and discussion of alternative conceptual and quantitative approaches
      that involve both a person-centered and a variable-centered component, and to
      make these methods more accessible to alcohol and other drug researchers. The
      first paper provides a general latent variable modeling framework within which to
      conceptualize developmental questions that involve the combination of continuous
      latent variables and categorical variables that represent classifications of
      individuals into meaningful subgroups. This is followed by three empirical papers
      that use integrative methods to examine early adult outcomes of adolescent binge
      drinking; potential mediators of familial alcoholism effects on alcohol and
      tobacco use disorder comorbidity; and the ability of psychopathology, substance
      use, and parental history of alcohol problems to predict individual differences
      in the likelihood of transitions in drinking behavior during adolescence. The
      section concludes with a discussion of the statistical basis for integrating
      person-centered and variable-centered methods, a comparison of study findings,
      and directions for future research.

PMID- 10888079
TI  - Integrating person-centered and variable-centered analyses: growth mixture
      modeling with latent trajectory classes.
AB  - BACKGROUND: Many alcohol research questions require methods that take a person
      centered approach because the interest is in finding heterogeneous groups of
      individuals, such as those who are susceptible to alcohol dependence and those
      who are not. A person-centered focus also is useful with longitudinal data to
      represent heterogeneity in developmental trajectories. In alcohol, drug, and
      mental health research the recognition of heterogeneity has led to theories of
      multiple developmental pathways. METHODS: This paper gives a brief overview of
      new methods that integrate variable- and person-centered analyses. Methods
      discussed include latent class analysis, latent transition analysis, latent class
      growth analysis, growth mixture modeling, and general growth mixture modeling.
      These methods are presented in a general latent variable modeling framework that
      expands traditional latent variable modeling by including not only continuous
      latent variables but also categorical latent variables. RESULTS: Four examples
      that use the National Longitudinal Survey of Youth (NLSY) data are presented to
      illustrate latent class analysis, latent class growth analysis, growth mixture
      modeling, and general growth mixture modeling. Latent class analysis of
      antisocial behavior found four classes. Four heavy drinking trajectory classes
      were found. The relationship between the latent classes and background variables
      and consequences was studied. CONCLUSIONS: Person-centered and variable-centered
      analyses typically have been seen as different activities that use different
      types of models and software. This paper gives a brief overview of new methods
      that integrate variable- and person-centered analyses. The general framework
      makes it possible to combine these models and to study new models serving as a
      stimulus for asking research questions that have both person- and variable
      centered aspects.

PMID- 10888080
TI  - Early adult outcomes of adolescent binge drinking: person- and variable-centered
      analyses of binge drinking trajectories.
AB  - BACKGROUND: Many studies of the consequences of binge drinking take a variable
      centered approach that may mask developmentally different trajectories. Recent
      studies have reported qualitatively different binge drinking trajectories in
      young adulthood. However, analyses of developmental trajectories of binge
      drinking have not been examined for an important period of drinking development:
      adolescence. The purpose of this study was to examine young adult outcomes of
      adolescent binge drinking using an approach that combines person-centered and
      variable-centered methods. METHODS: Data were from the Seattle Social Development
      Project, an ethnically diverse, gender balanced sample (n = 808) followed
      prospectively from age 10 to age 21. Semiparametric group-based modeling was used
      to determine groups of binge drinking trajectories in adolescence. Logistic
      regression was used to examine how well the trajectory groups predicted young
      adult outcomes after demographics, childhood measures, and adolescent drug use
      were considered. RESULTS: Four distinct trajectories of binge drinking during
      adolescence were identified: Early Highs, Increasers, Late Onsetters, and
      Nonbingers. These trajectories significantly predicted positive and negative
      outcomes in adulthood after controlling for demographic characteristics, early
      proxy measures of the outcome, and adolescent drug use. CONCLUSIONS: This
      integrated person- and variable-centered approach provides more information about
      the effects of specific patterns of binge drinking than studies that employ
      variable-centered methods alone.

PMID- 10888081
TI  - Trajectories of concurrent substance use disorders: a developmental, typological
      approach to comorbidity.
AB  - BACKGROUND: Although alcohol and tobacco use disorders are highly comorbid,
      little is known regarding the combined course of these disorders. METHODS: The
      current study utilized latent class analysis to examine longitudinal patterns of
      alcohol-tobacco use disorder comorbidity. Participants were 449 young adults
      (baseline age, 18.5 years; 48% male; 51% with paternal history of alcoholism)
      assessed five times over 7 years. RESULTS: Five longitudinal types of alcohol or
      tobacco use disorder over time were identified: nondiagnosing; developmentally
      limited alcohol use disorder; chronic alcohol use disorder; chronic tobacco use
      disorder; and comorbid alcohol and tobacco use disorder. These typologies were
      distinguishable on the basis of family history of alcoholism status and sex.
      Etiologically important third variables (alcohol expectancies, behavioral
      undercontrol, childhood stressors) mediated the relation between family history
      and the latent classes. CONCLUSIONS: Characterizations of alcohol use disorders
      typically fail to consider important sources of heterogeneity such as course or
      comorbidity. By simultaneously modeling developmental course and comorbidity with
      tobacco dependence, we were able to identify distinct trajectories of single and
      concurrent substance use disorders. Such multi-substance trajectories represent
      meaningful subtypes that, although sharing substantial common influences, have
      unique etiologic correlates. Additionally, these subtypes might represent
      distinct groups from the perspective of intervention strategies.

PMID- 10888082
TI  - Transitions in drinking in adolescent females: evidence from the Missouri
      adolescent female twin study.
AB  - BACKGROUND: Data from adult community samples indicate that alcohol dependence
      originates in late adolescence, thus marking that period as a fruitful one for
      the study of transitions in drinking. METHODS: Using retrospective data about the
      timing of alcohol symptom onset from 1799 female twins who participated in the
      Missouri Adolescent Female Twin Study (MOAFTS), we integrated person-centered
      (PC) and variable-centered (VC) analyses to study 1-year transitions in alcohol
      symptomatology. A person-year data set reflecting the onset of 15 alcohol
      dependence symptoms was constructed, with each year in the young woman's life
      from the year of her first drink to her current age counting as one observation.
      Latent class analysis--a PC technique--identified classes of alcohol
      symptomatology for each person-year, and a lag function was used to identify
      class membership 1 year earlier. One-year transitions in drinking--a VC analysis-
      were then studied. RESULTS: Smoking, marijuana use, and conduct problems were
      consistent promoters of transitions to more severe drinking classes, but
      depressed affect was not a significant predictor. Parental history of alcohol
      problems or excessive drinking, particularly maternal history, was a significant
      predictor of more serious transitions to moderate and dependent problem drinking.
      CONCLUSIONS: These data confirm that even over a 1-year time frame there was
      considerable change in drinking patterns in this adolescent sample. Smoking was
      as potent a risk factor as conduct problems in promoting the progression of
      alcohol symptomatology, and the role of familial factors was found to be
      influential in transitions at the more severe end of the drinking spectrum.

PMID- 10888083
TI  - Comments on integrating person-centered and variable-centered research on
      problems associated with the use of alcohol.
AB  - For any sample of m different variables obtained on a sample of n different
      persons, there is an identity transformation between classifications of persons
      (types) that are defined with person-centered methods and classifications of
      variables (factors) defined with variable-centered methods: types are manifested
      in factors and factors are expressed in types. Both kinds of methods analyze the
      variability-the same variability-in a persons-by-variables data matrix. Person
      centered types can be transformed into variable-centered factors. Thus, at a
      basic level there is a basis for integrating person-centered and variable
      centered research. But there are many different ways to implement person-centered
      methods, just as there are many different ways to resolve variables into factors,
      and generally any model for analysis directed at identifying types will not be
      the complement of a model selected for analysis leading to factors. Thus, while
      the results from the two kinds of analysis can be related to one another, the
      results they produce in applications can be quite different. Also, in practice,
      one method is used before the other. For example, person-centered methods might
      be used to form types, which are then studied with multiple-group, variable
      centered methods to test hypotheses specifying invariance or differences of
      relationships across types. There are good reasons to think in terms of types as
      one contemplates analysis in terms of variables. But the reverse also is true. In
      typological analysis, it must be assumed that types exist and that samples of
      subjects and indicator variables are drawn in ways that can reveal this.
      Different typologies indicated by person-centered research are most concretely
      compared if the different studies use comparable sets of persons, indicator
      variables, and other variables that can indicate correlates. Strictly speaking,
      none of these sets were comparable in the three substantive studies reviewed
      here. Nevertheless, at an abstract level it was possible to see that the results
      of the three studies agreed in indicating that there is a type of adolescent and
      young adult that, by and large, does not have-or at least does not report having
      problems associated with the use of alcohol. This type is in the majority,
      accounting for approximately 60% of the youth sampled in the reviewed studies.
      The studies agree also in suggesting that types may emerge along a continuum of
      maladjustment characterized by increasing use of alcohol and other drugs,
      failures in school, problems at home, interpersonal difficulties, delinquency,
      and legal problems. Variable-centered dynamic analyses might further describe
      phenomena of this kind.

PMID- 10888084
TI  - Impact of preoperative left ventricular ejection fraction on postoperative left
      ventricular remodeling after mitral valve repair for degenerative disease.
AB  - BACKGROUND AND AIM OF THE STUDY: Mitral valve repair has been associated with
      better preservation of left ventricular (LV) function, especially in the setting
      of degenerative regurgitation. The goal of this study was to evaluate the impact
      of mitral valve repair on postoperative LV ejection fraction (LVEF) and LV
      remodeling as determined by LV end-systolic and diastolic diameters. METHODS: A
      prospective echocardiographic and clinical evaluation of 91 patients undergoing
      mitral valve repair for degenerative regurgitation between 1993 and 1998 was
      performed. Patients with normal preoperative LVEF (> or = 50%; group 1, n = 71)
      were compared with patients with decreased preoperative LVEF (< 50%; group 2, n =
      20) one year after mitral valve repair. RESULTS: In group 1 patients, the LVEF
      was preserved at one year, while the LV end-systolic diameter was significantly
      reduced from 36 +/- 7 mm to 32 +/- 8 mm (p <0.05). There was a significant
      improvement in LVEF in group 2 patients (38 +/- 6% preoperative versus 50 +/- 12%
      at one year, p <0.05). The preoperative LV end-systolic diameter was
      significantly larger in group 2 patients (47 +/- 9 mm) than in group 1 patients
      (36 +/- 7 mm) (p <0.001), but decreased to normal values at one year after repair
      (38 +/- 7 mm, p <0.05). CONCLUSION: There was good preservation of LV function
      after mitral valve repair in group 1 patients. The LVEF significantly increased
      towards normal in patients with depressed LV function before repair. The LV
      systolic diameter was restored to normal within one year of repair, even in
      patients with poor LV function. Decreased preoperative LV function should not be
      a contraindication to mitral valve repair in patients with degenerative
      regurgitation.

PMID- 10888085
TI  - Mitral valve annuloplasty for degenerative disease: assessment of four different
      techniques.
AB  - BACKGROUND AND AIM OF THE STUDY: Mitral valve repair (MVR) is the treatment of
      choice in patients with degenerative valve disease. However, controversy persists
      as to whether mitral valve annuloplasty should always be included as part of the
      reconstructive procedure. METHODS: The records of 62 consecutive patients
      undergoing MVR for degenerative disease between January 1994 and December 1996
      were reviewed. Four different annuloplasty techniques were associated with
      various MVR procedures: local posterior annuloplasty (group 1, n = 10), rigid
      Carpentier ring (group 2, n = 20), Duran ring (group 3, n = 17), and posterior
      annular plication with autologous pericardium (group 4, n = 15). The four patient
      groups were similar in terms of preoperative clinical and echocardiographic
      characteristics. Serial clinical and echocardiographic follow up was performed to
      assess functional status and stability of repair. RESULTS: There were no early or
      late deaths. Mean follow up in the entire patient series was 31 +/- 12 months.
      One patient in group 2 required reoperation 14 months after MVR. In all groups
      there was a significant improvement in NYHA functional class (from 2.7 +/- 0.6 to
      0.9 +/- 0.5, p <0.001), with a reduction of left ventricular end-diastolic and
      end-systolic volumes (154 +/- 50 ml to 105 +/- 33 ml, p <0.001; and 64 +/- 23 ml
      to 52 +/- 22 ml, p <0.001). In patients of groups 2, 3 and 4, residual mitral
      incompetence at follow up (0.8 +/- 0.9 in group 2, 0.8 +/- 0.7 in group 3, and
      0.2 +/- 0.6 in group 4) was not significantly different from discharge. However,
      in group 1, a higher degree of residual mitral regurgitation was present at
      discharge (0.9 +/- 0.6) with a trend to progress at follow up (1.6 +/- 0.5).
      CONCLUSION: In patients with degenerative mitral valve disease, MVR provides
      clinical and functional improvement. Techniques of stabilization of the entire
      posterior mitral annulus achieve better early and medium-term results, and should
      be always considered as part of MVR. Autologous pericardium appears to be an
      excellent annuloplasty material, though its apparent superiority over synthetic
      rings must be confirmed at longer follow up.

PMID- 10888086
TI  - Surgical treatment of infective mitral valve endocarditis: predictors of early
      and late outcome.
AB  - BACKGROUND AND AIMS OF THE STUDY: The study aim was to review our experience in
      surgical treatment of infective mitral valve endocarditis, and to identify
      predictors of early and late outcome. METHODS: Ninety-one consecutive patients
      (52 males, 39 females, mean age 55.6 years) underwent surgery between 1973 and
      1997 for endocarditis of isolated mitral (n = 65, 71%), mitral and aortic (n =
      25, 28%) and mitral, aortic and tricuspid valves (n = 1, 1%). Native valve
      endocarditis (NVE) was present in 60 patients (66%) and prosthetic valve
      endocarditis (PVE) in 31 (34%). The main indications for surgery were heart
      failure in 32 patients, valve dysfunction in 23, vegetations in 21, and
      persistent sepsis in 11. Eighty-six patients (95%) were in NYHA classes III-IV,
      and 58 (64%) had active culture-positive endocarditis at surgery. Mechanical
      valves were implanted in 73 patients and bioprosthetic valves in 13; valves were
      repaired in five patients. The impact of 46 parameters on early and late outcome
      was defined by means of univariate and multivariate statistical analysis. Follow
      up was complete (mean 5.5 years; range: 0-23.1 years; total 507.3 patient-years).
      RESULTS: Operative mortality rate was 11% (n = 10). Recurrent infection was
      recorded in five patients (6%), and reoperation was required in eight (9%).
      Freedom from recurrent infection and reoperation at 10 years was 89.1% and 87.8%
      respectively. There were 22 late deaths, 15 from cardiac causes. Actuarial
      survival rates for all patients at 5, 10 and 15 years were 73.0%, 62.7% and 58.7%
      (for hospital survivors, the corresponding rates were 81.9%, 69.7% and 66.0%). On
      multiple logistic regression and Cox proportional hazards models, the following
      were independent predictors: preoperative pulmonary edema (p = 0.01) for
      operative mortality; PVE (p = 0.02) for recurrence; younger age (p = 0.02) and
      PVE (p = 0.02) for reoperation; male gender (p = 0.004) and longer ITU stay for
      survival (if all patients were included); male gender (p = 0.01) and myocardial
      invasion by infection (p = 0.02) for survival (if only the hospital survivors
      were analyzed). CONCLUSION: Surgery for infective mitral valve endocarditis
      carries a relatively high, though acceptable, risk but provides satisfactory
      freedom from recurrent infection, reoperation and improved long-term survival.
      Analysis of these data demonstrated that the preoperative hemodynamic status was
      the major predictor of in-hospital outcome, PVE increased the risk for recurrent
      infection and reoperation, whereas male gender and myocardial invasion by the
      infective process critically reduced the probability of long-term survival. The
      type of offending pathogen, the activity of infection and the involvement of more
      than one valve did not appear to influence early and/or late outcome.

PMID- 10888087
TI  - Mid-term follow up of mitral valve reconstruction due to active infective
      endocarditis.
AB  - BACKGROUND AND AIM OF THE STUDY: Mitral valve reconstruction in patients with
      acute endocarditis (AE) is a challenging operation which prompts the surgeon into
      immediate action. This report summarizes the mid-term results of 22 patients who
      required mitral valve reconstruction due to AE. METHODS: Mean patient age was 46
      years (range: 20-79 years); mean follow up was 46 months (range: 1-90 months).
      Preoperatively, >70% of patients had severe mitral regurgitation and were in NYHA
      functional class III. Surgical techniques used were annuloplasty (n = 16; 10 with
      Carpentier ring, five Wooler-Kay and one Frater); suture closure of the
      perforation (n = 1), patch closure of the perforation (n = 5), leaflet resection
      with primary closure (n = 2), leaflet resection with patch closure (n = 8), and
      chordal transfer (n = 3). Additional surgery included CABG (n = 3) and De Vega
      plasty (n = 4). Aortic valve replacement or reconstruction (n = 9) included one
      mechanical valve, one bioprosthesis, one reconstruction and six homografts.
      Patients were followed up annually in our outpatient department and/or by
      questionnaires. RESULTS: Two patients died perioperatively due to either low
      output syndrome or uncontrolled sepsis. There were three reoperations; two of
      these were successful, and one patient subsequently died. In addition, one
      patient died six years after operation due to prostatic cancer, and one seven
      years later due to progressive heart failure. At the last follow up, 15 patients
      were in NYHA class I (68%) and five in class II (23%); no or only mild mitral
      insufficiency was seen on transthoracic echocardiography (91%). The estimated
      survival rate at 60 months was 87 +/- 12.7%, and 12 patients were followed up for
      >60 months. No incidence of recurrent valve infection occurred. CONCLUSION:
      Mitral valve reconstruction in patients with AE shows a low incidence of valve
      related complications with promising postoperative functional results and mid
      term survival. On this basis, mitral valve reconstruction for mitral
      insufficiency secondary to AE may be recommended as a valve salvage treatment,
      when it is technically possible.

PMID- 10888088
TI  - Usefulness of three-dimensional echocardiography for the evaluation of mitral
      valve prolapse: an intraoperative study.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the feasibility of
      intraoperative three-dimensional (3D) transesophageal echocardiography (TEE) in
      patients referred for mitral valve prolapse (MVP) repair and to compare two
      dimensional (2D) TEE and 3D TEE and surgical findings. METHODS: Forty-six
      patients (mean age 67 +/- 11 years) underwent 3D TEE intraoperatively.
      Measurements were made of the posterior part of mitral annulus circumference
      (PMAC), and the width of mitral valve surgical resection on the mitral annulus
      (WMVR). Using 3D TEE, MVP topography was described, and PMAC in diastole and the
      width of implantation of MVP on the mitral annulus (WMVP) in systole were
      measured. RESULTS: 3D TEE was successful in 42 patients (91%). 2D and 3DTEE
      correctly predicted MVP localization in 38 (90%) and 36 (86%) patients,
      respectively (p = NS). 3D TEE and surgical PMAC were 89 +/- 13 and 93 +/- 21 mm,
      respectively (p = 0.01, R = 0.42). WMVR and WMVP were 28 +/- 11 mm and 26 +/- 11
      mm, respectively (p <0.0001, R = 0.82). WMVR/anatomic PMAC (0.29 +/- 0.11) and
      WMVP/3D echo PMAC (0.32 +/- 0.11) were correlated (p <0.0001, R= 0.69).
      CONCLUSION: Intraoperative 3D TEE evaluation of MVP is feasible. MVP width and
      its ratio to the mitral annulus were assessed, and found to correlate with
      surgical findings. These 3D data may be of value to the surgeon when performing
      mitral valve repair.

PMID- 10888089
TI  - Transfer of the posterior leaflet of the tricuspid valve to the mitral valve.
AB  - BACKGROUND AND AIM OF THE STUDY: Coverage of large commissural defects may
      present a surgical challenge in mitral valve repair, for which the transfer of
      posterior tricuspid valve leaflet tissue is an attractive approach. METHODS: Five
      patients aged between 35 and 55 years underwent this procedure. After wide
      excision of the diseased mitral commissures, the posterior leaflet of the
      tricuspid valve was carefully checked, removed with its subvalvular apparatus,
      and transferred to the commissural area of the mitral valve. The stress on the
      papillary muscle suture was relieved by reinforcement of the free edge of the
      transferred leaflet by natural or artificial chordae. The tricuspid valve was
      repaired using either a sliding plasty or an annuloplasty. RESULTS: One patient
      who had no reinforcement of the subvalvular apparatus had a papillary muscle
      rupture and required mitral valve replacement during the early postoperative
      period. The four remaining patients remained asymptomatic and had no or trivial
      mitral regurgitation after a median of 13 months (range: 3-18 months), with
      excellent result at transesophageal echocardiography. CONCLUSION: We conclude
      that transfer of the tricuspid valve leaflet allows coverage of large commissural
      defect, and deserves a place among the surgeon's arsenal of reconstructive
      techniques for mitral valve repair.

PMID- 10888090
TI  - Trivalvular/bivalvular heart: a philosophical, scientific and therapeutic
      concept.
AB  - BACKGROUND AND AIM OF THE STUDY: In 1967, following the replacement of infected
      tricuspid valves in drug addicts with incurable endocarditis, all patients died.
      The study aim was to determine if tricuspid valve removal, rather than
      replacement, might offer these patients an improved outcome. METHODS: Since July
      1970, we have operated on 55 patients with intractable right-sided endocarditis.
      Before surgery, all had a history of intravenous drug abuse (IVDA) (duration
      range: 2-20 years; 5 years in 38 cases). In 53 patients the tricuspid valve was
      excised without replacement; the pulmonary valve was also removed in two cases.
      RESULTS: Six (11%) patients died within six weeks of surgery, and 11 died between
      six months and 24.5 years. Ten of the late deaths were related to IVDA. Among 49
      patients who survived surgery for six months to 29 years, 24 (50%) returned to
      the use of illicit drugs. Only six patients eventually required insertion of a
      heart valve prosthesis; of these, four died, two due to repeat IVDA. Of 38 long
      term survivors (range: 9-29 years), two have a non-functioning bioprosthesis in
      the tricuspid position, 35 have a trivalvular heart, and one has a bivalvular
      heart. Only three patients required diuretics and digitalis. CONCLUSION: IVDA
      patients with intractable right-sided infective endocarditis have the best chance
      of cure and long-term survival by undergoing tricuspid or tricuspid and pulmonary
      valve excision(s), without prosthetic replacement. No published evidence or long
      term follow up data indicate better surgical treatment for this patient group. In
      this day and age of cost containment, these operations are economical. Operations
      that work well in non-addicted patients become costly and invariably are
      associated with a second endocarditis and death in inveterate IVDA cases.

PMID- 10888091
TI  - Pulmonary valve endocarditis: mid-term follow up of pulmonary valvectomies.
AB  - Four males aged 20-37 years (three drug addicts and one with a congenital mixed
      pulmonary valve lesion) were diagnosed in 1989, 1991 and 1993 with pulmonary
      valve endocarditis without tricuspid infection. Three patients were positive for
      hepatitis B, C or both, and one patient was HIV-positive. The predominant
      organism in blood cultures was Staphylococcus aureus. Antibiotic treatment of
      pulmonary valve endocarditis had failed; thus partial or total valvectomies were
      performed. Postoperatively, all patients were cured of infection and initial
      recovery was good. At mid-term follow up (5-10 years) there were no recurrences,
      and tolerance of the resultant pulmonary insufficiency was good. Slight to severe
      tricuspid valve insufficiency developed, together with right ventricular
      dilatation, in all cases. Hepatomegaly was apparent in two cases and peripheral
      edema in one. Despite treatment, the latter patient remained in moderate right
      ventricular failure, and may require homograft valve replacement. The other three
      patients remained in good clinical condition. Eradication of the infection was
      achieved in all patients. It is concluded that pulmonary valve resection is the
      treatment of choice for pulmonary valve endocarditis when antibiotic treatment
      has failed. Complete resection of all affected tissue should be performed in
      these cases. Analysis of preoperative data did not permit differentiation of
      those patients likely to develop right heart failure.

PMID- 10888092
TI  - Calcification and degeneration following mitral valve reconstruction in patients
      requiring chronic dialysis.
AB  - BACKGROUND AND AIM OF THE STUDY: Abnormal calcium homeostasis in patients with
      end-stage renal failure results in dystrophic calcification; this limits the use
      of heterograft tissue valve prostheses in patients on chronic dialysis. Mitral
      valve reconstruction offers advantages over mitral replacement in many patients
      without renal failure, and offers theoretical advantages in patients requiring
      dialysis. This study was performed to determine the outcome of mitral valve
      reconstruction in patients with renal failure requiring chronic dialysis.
      METHODS: Ten patients with end-stage renal failure and on chronic dialysis who
      underwent mitral valve repair were identified retrospectively and followed for
      clinical and echocardiographic outcome. All patients had good results immediately
      following surgical valve mitral repair, with no more than mild mitral
      regurgitation and low transmitral gradients on intraoperative transesophageal
      echocardiography. RESULTS: Clinical and echocardiographic follow up was available
      for eight patients at an average of 2.3 +/- 1.4 years after surgery. Despite
      there being no significant valve calcification at the time of surgery, visible
      mitral leaflet calcification was evident in seven of these patients, and the
      transmitral gradient for the group was significantly increased (from 4.8 +/- 1.7
      mmHg to 8.3 +/- 3.9 mmHg, p = 0.04). Two patients required reoperation for failed
      mitral repair; one at six months due to chordal rupture, and one at 15 months due
      to mitral calcification with stenosis. CONCLUSION: Despite good early surgical
      results, there was accelerated calcification of the repaired mitral valve, a
      rapid increase in postoperative mitral gradients, and a high incidence of failure
      of the reconstruction. Additional prospective studies are required to evaluate
      the optimal intervention for patients with end-stage renal failure who require
      mitral valve surgery.

PMID- 10888093
TI  - Aortic valve replacement with bioprostheses in liver transplant recipients.
AB  - Three cases of aortic valve replacement with porcine bioprostheses are reported
      in liver transplant recipients at two to six years after transplantation.
      Indications for aortic valve replacement (AVR) were aortic stenosis (n = 2) and
      aortic regurgitation (n = 1). The use of bioprostheses was recommended because of
      patient age, the need for multiple liver biopsies, and contraindication to the
      use of anticoagulation therapy. The patient who underwent AVR because of aortic
      regurgitation developed structural valve deterioration (SVD) during the next five
      years after surgery, and thus replacement of the bioprosthetic valve was
      required. Recipients of liver transplant who undergo valve replacement with
      tissue valves should be carefully followed up because of the risk of early SVD.
      AVR may be performed safely after liver transplantation.

PMID- 10888094
TI  - The use of transesophageal echocardiography guidance of thrombolytic therapy in
      prosthetic mitral valve thrombosis.
AB  - BACKGROUND AND AIM OF THE STUDY: The aim of the study was to assess the use of
      transesophageal echocardiography (TEE) to guide thrombolytic therapy in
      prosthetic mitral valve thrombosis. METHODS: Twenty-nine consecutive cases of
      prosthetic mitral valve thrombus diagnosed between January 1995 and May 1998 were
      managed according to data obtained by TEE. Three patients with pedunculated
      thrombus and five in NYHA functional classes I-II were referred for surgery.
      Patients who refused surgery or who were in NYHA classes III-IV and had
      unpedunculated thrombus were selected for thrombolytic therapy. Twenty-one
      patients (seven males, 14 females; mean age 47 +/- 8 years) received
      streptokinase for thrombolysis. RESULTS: The mean period from valve replacement
      surgery was 36 +/- 23 months, and mean time from onset of symptoms 9.2 +/- 14.3
      days. Anticoagulant use was inadequate in 18 (86%) patients. Fourteen cases (66%)
      were NYHA class IV, four (19%) in class III, and three (15%) in class II. Ten
      patients (48%) were in atrial fibrillation. During the first 24 h of thrombolytic
      therapy, mean mitral valve peak and mean gradients fell from 25.6 +/- 4 and 13.8
      +/- 2.5 mmHg to 11.7 +/- 5.3 and 7.1 +/- 3.1 mmHg respectively (p <0.0001). Five
      cases with inadequate response to thrombolysis were treated for an additional 24
      h. The mitral valve area increased from 1.0 +/- 0.1 cm2 to 2.3 +/- 0.7 cm2 after
      the first month (p <0.0001). Complete early success in thrombolysis was achieved
      in 17 (81%) cases, three cases (14%) had partial success, and one case (5%) was
      referred for surgery on the third day because of failed thrombolysis. Two minor
      skin bleedings (9%) not requiring transfusion were attributed to thrombolytic
      therapy. One case (5%) of successful thrombolysis had a non-fatal stroke after
      therapy and one (5%) was referred for surgery for recurrent prosthetic mitral
      valve thrombosis at six months' follow up. None of the surgically treated
      patients died. CONCLUSION: Guidance of thrombolysis by TEE may reduce, but not
      eliminate, the risk of thromboembolic complications. Response to thrombolysis
      became apparent within 24 h, but extending treatment beyond this time provided no
      additional short-term benefit.

PMID- 10888095
TI  - Ultrasonic determination of clot deposition rates in a milk-based, in-vitro
      procedure for thrombogenicity assessment.
AB  - BACKGROUND AND AIM OF THE STUDY: Thrombosis and thromboembolism remain the main
      problems associated with mechanical heart valves. We have devised a milk-based
      clotting technique to simulate in-vitro clinical incidence of thrombosis. Early
      results with the technique revealed good correlation between milk clot deposition
      and clinical thrombosis, but were limited in their ability to predict the course
      of clot deposition, as deposition could only be measured upon dismantling the
      apparatus. METHODS: Clot deposition was observed ultrasonically for both steady
      and pulsatile flows of a milk preparation through a cylindrical test chamber
      containing axisymmetric test bodies similar in shape to those used in earlier
      studies of thrombosis. Echo ultrasound images were recorded at regular time
      intervals, depicting the interface between clot deposits and flowing milk. From
      these images, the thickness of the clot deposit could be determined as a function
      of time. RESULTS: Milk clot deposition on the test bodies, while observed, could
      not be measured accurately due to faint reflections arising from significant
      differences between the angle of incidence and the angle of reflection of the
      ultrasound beam. However, measurement was possible at the wall of the test
      chamber where deposition rates revealed steady growth of clot, following an
      initial 'lag', with growth continuing until a maximum thickness is reached. In
      some experiments shedding of parts of the deposit was observed. In pulsatile
      flow, wall clot deposition rates and final clot thickness attained were
      significantly lower than in steady flow. CONCLUSION: Ultrasonic measurement of
      clot deposition rates is possible in our thrombogenicity assessment apparatus on
      surfaces perpendicular to the line of incidence of the ultrasound beam. With
      suitably designed viewing windows in an artificial heart, such measurements
      should enable the time course of clot deposition on artificial valves to be
      determined, with a view to identifying initial deposition sites and the dynamics
      of clot growth. Observations of the growth of clot on the test chamber wall in
      this study suggest that both the rate of deposition and nature of deposit formed
      are strongly influenced by fluid mechanical properties such as shear and mass
      transfer rates. In particular, our results appear to suggest a different
      structure of deposit, whose rate of deposition is relatively slow, under
      conditions of high shear.

PMID- 10888096
TI  - Mid-term results with 1,503 CarboMedics mechanical valve implants.
AB  - BACKGROUND AND AIM OF THE STUDY: The CarboMedics bileaflet prosthetic heart valve
      was introduced in 1986, and first implanted by the authors in March 1991. The aim
      of this study was to analyze the authors' clinical experience with this valve.
      METHODS: Between March 1991 and October 1998, 1,503 valves were implanted in
      1,350 patients (758 males, 592 female; mean age 62 +/- 13 years). Follow up was
      99% complete and totaled 4,342 patient-years (pt-yr). RESULTS: The hospital
      mortality rate was 4.3% (59/1,350). Preoperative NYHA class (p = 0.012),
      emergency surgery (p = 0.03) and cardiopulmonary bypass time (p = 0.01) were
      significantly associated with increased risk of operative death (multiple
      logistic regression). Mean (+/- SEM) survival rates at one and five years were
      92.0 +/- 0.7% (n = 1,109) and 80.0 +/- 1.3% (n = 335). Freedom from valve-related
      complications (linearized rate 5.6%/pt-yr) at one and five years was 89.5 +/-
      0.8% (n = 1,031) and 76.3 +/- 1.4% (n = 284). Linearized rates for bleeding
      events were 2.19%/pt-yr, thromboembolic events 2%/pt-yr, operated valvular
      endocarditis 0.18%/pt-yr, valve thrombosis 0.14%/pt-yr and non-structural
      dysfunction 1.22%/pt-yr. Freedom from reoperation at one and five years was 98.5
      +/- 0.3% (n = 1,107) and 97.3 +/- 0.5% (n = 334). CONCLUSION: Mid-term results
      demonstrate that the CarboMedics prosthetic heart valve exhibits a low incidence
      of valve-related complications.

PMID- 10888097
TI  - Mid-term clinical and echocardiographic follow up of patients with CarboMedics
      valves in the tricuspid position.
AB  - BACKGROUND AND AIM OF THE STUDY: Debate continues regarding tricuspid valve
      replacement (TVR) with a mechanical prosthesis. Experience with bileaflet
      prostheses is limited; hence the study aim was to explore early and mid-term
      outcome and hemodynamic data in patients with bileaflet CarboMedics prosthetic
      valves in the tricuspid position. METHODS: The study population included 25
      patients (21 females, four males; mean age 50.5 +/- 13.4 years) who underwent TVR
      with a CarboMedics valve over a six-year period. Routine clinical examinations
      and details of transthoracic echocardiography (TTE) were reviewed. Additional
      TTE, transesophageal echocardiography (TEE) and fluoroscopy were performed as
      indicated. The number of previous cardiac operations was zero, one and two in
      36%, 32% and 32% of patients, respectively. Previous tricuspid surgery was
      performed in eight cases (32%); concurrent mitral valve replacement was performed
      in 17 (68%). The hospital mortality rate was 24% and late mortality rate 12%.
      Seventeen early survivors (13 females, four males) were followed up for 46 +/- 28
      months (range: 4-96 months). RESULTS: Among early survivors, the mean and peak
      transvalvular gradients were 4.0 +/- 1.7 and 7.9 +/- 3.3 mmHg, respectively.
      Commonly observed INR levels were >2.5 in seven patients (41%), and >3.0 in only
      three (18%). Five patients (29% of mid-term survivors) experienced a total of 13
      episodes of obstructive valve thrombosis, mostly with inappropriate
      anticoagulation. One patient required emergency re-do surgery; the others
      responded initially to thrombolysis or intensified antithrombotic treatment, but
      experienced at least two additional relapses. Aside from thrombotic episodes, all
      patients but two were in NYHA functional class II-III, and all but four required
      diuretics. CONCLUSION: TVR with bileaflet mechanical valves carries a high
      perioperative mortality and mid-term morbidity. Among patients with poor or fair
      anticoagulation, these valves were associated with a high incidence of
      obstructive valve thrombosis. If poor patient compliance is anticipated,
      insertion of a bioprosthesis should be encouraged.

PMID- 10888098
TI  - Comparison of On-X and SJM HP bileaflet aortic valves.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the hemodynamic
      function after aortic valve replacement (AVR) using the On-X valve, in comparison
      with St. Jude Medical (SJM) HP bileaflet valves. METHODS: Patients received
      either the On-X (n = 20) or SJM HP prosthesis (n = 20) for AVR. The control (SJM
      HP) group was computer-matched with the On-X group for age, gender, aortic
      stenosis as underlying disease, body surface area, NYHA functional class, left
      ventricular size, mass and function, transvalvular pressure gradients and cardiac
      index. Mean implanted valve size was 23.5 mm (three 21 mm, ten 23 mm, six 25 mm,
      one 27 mm) in both groups. All patients underwent postoperative, and six- and 12
      month follow up echocardiography. RESULTS: The intra- and postoperative course
      was uneventful in all patients. There were no significant differences in cross
      clamp and cardiopulmonary bypass times, intensive care unit stay, in-hospital
      stay and postoperative NYHA functional class. Two patients (both On-X) had
      paravalvular leakage postoperatively and at follow up. Five patients in the
      control group had additional myocardial revascularization. Transvalvular flow
      velocities were 2.38 +/- 0.3 versus 2.38 +/- 0.4 m/s (p = NS) postoperatively,
      and 2.08 +/- 0.2 versus 2.22 +/- 0.3 m/s (p = NS) at one year follow up for On-X
      and SJM HP valves, respectively. Maximum pressure gradients were 16.9 +/- 6.0
      versus 18.5 +/- 8.0 mmHg (p = NS) postoperatively and 14.0 +/- 3.7 versus 16.5 +/
      5.7 mmHg (p = NS) at one year for the two valve types, respectively. A
      relatively pronounced transvalvular reflux was diagnosed for On-X valves.
      CONCLUSION: At one year after implantation, the On-X bileaflet prosthesis is
      equally suited for AVR in comparison with the 'standard' therapy (SJM HP). Exact
      sizing requires some experience. There were no significant differences between
      the two prostheses with regard to hemodynamic parameters either postoperatively
      or at one-year follow up. Long-term prospective randomized studies yet have to be
      carried out.

PMID- 10888099
TI  - ATS prosthetic valve motion: an in vitro analysis.
AB  - BACKGROUND AND AIM OF THE STUDY: We have reported clinical findings that normally
      functioning open pivot ATS valves did not open completely. In order to analyze
      features of the ATS valve motion more precisely, in vitro tests were conducted.
      METHODS: Opening angles and pressure gradients of the ATS valve were measured and
      compared with those of the St. Jude Medical (SJM) valve under steady flow, but
      with various outlet configurations. Second, opening angles of the two valves were
      measured under pulsatile conditions in two different outflow configurations: (i)
      a 'straight outlet' where the leaflets did not extend into the tapering outflow
      chamber, and (ii) an 'abrupt enlargement outlet' where the leaflets extended
      directly into the enlarged outflow space. Third, flow visualization studies were
      made under steady flow conditions in the straight and abrupt enlargement outlet
      conduits, respectively. RESULTS: Under steady flow conditions, opening of the ATS
      valve was restricted in most outflow configurations; only when the outlet angle
      was 0 degrees did the valve open fully. The SJM valve opened completely in all
      downstream configurations. Despite restricted opening in the ATS valve, the
      pressure gradient was similar in both valves. Under pulsatile conditions, both
      valves opened fully in the straight outlet; however, in the abrupt enlargement
      outlet the ATS valve opened incompletely and the SJM valve completely.
      Substantial turbulent flow was observed at the outside of the leaflet and corners
      of the conduit, notably with the ATS valve. CONCLUSION: This study showed that
      the ATS valve did not open fully except when the outflow was straight, and the
      leaflet did not extend into an enlarged downstream chamber. Structural features
      of the ATS, such as its axis being located close to the straight edge and its
      leaflets extending further downstream from the ring orifice, may cause this
      unique valve behavior.

PMID- 10888100
TI  - Fifteen years follow up with the St. Jude Medical Biocor porcine bioprosthesis.
AB  - BACKGROUND AND AIM OF STUDY: The study aim was to review the 15-year results of
      aortic (AVR) and mitral (MVR) valve replacement with the St. Jude Medical Biocor
      porcine prosthesis, in order to investigate long-term survival and valve-related
      complications. METHODS: Between January 1983 and January 1998, a total of 1,187
      patients underwent either AVR (n = 1,029; mean age 69 years) or MVR (n = 158;
      mean age 63 years). Follow up (99.7% complete) was monitored in 1998, and all
      data were analyzed with regard to actuarial valve failure rates. Long-term
      echocardiographic data were obtained. RESULTS: Cumulative follow up time was
      5,049 patient-years (pt-yr) for AVR patients, and 845 pt-yr for MVR patients.
      Actuarial survival rate at 15 years was 41 +/- 3%, and freedom from valve-related
      death was 94 +/- 1% for the AVR group; corresponding values for the MVR group
      were 25 +/- 11% and 84 +/- 6%. The occurrence of structural valve deterioration
      (SVD) varied with age; older patients were less affected. Freedom from SVD was 76
      +/- 7% and 92 +/- 4% for AVR and MVR patients, respectively. Thromboembolism (TE)
      occurred mainly among the oldest patients, and was most prevalent among those
      with MVR. Actuarial freedom from TE was 82 +/- 5% after AVR and 75 +/- 7% after
      MVR. Prosthetic valve endocarditis (PVE) was rare, but caused the only
      reoperative mortality. Freedom from PVE was 95 +/- 2% after AVR and 93 +/- 3%
      after MVR. CONCLUSION: Although the optimal valve substitute remains to be found,
      this long-term study of a third-generation bioprosthesis showed a low incidence
      of valve-related complications, especially of valve deterioration. This type of
      bioprosthesis appears to be more durable than valves of previous generations.

PMID- 10888101
TI  - Ten-years' clinical experience with the Sorin Pericarbon valve.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate 10 years' results
      obtained with the Pericarbon pericardial bioprosthesis. METHODS: Between
      September 1988 and December 1997, 277 patients (mean age 75.8 +/- 8.5 years)
      received a total of 287 Pericarbon pericardial valves. Of these patients, 224
      (80.8%) underwent single aortic valve replacement (AVR) and 39 single mitral
      valve replacement (MVR); one patient had a tricuspid valve replacement (TVR),
      three patients had a pulmonary valve replacement (PVR) and 10 had both aortic and
      mitral valve replacement (DVR). Associated cardiac procedures were performed in
      86 patients (31.0%), mainly coronary artery bypass graft (n = 71). Mean patient
      follow up was 4.9 +/- 2.6 years; total cumulative follow up was 1,221.4 patient
      years. RESULTS: The overall hospital mortality rate was 10.1%. There were 50 late
      deaths (20.1%), four (1.6%) being valve-related. The patient survival rate at
      10.8 years was 60.0 +/- 4.5% for AVR and 46.5 +/- 11.9% for MVR. Freedom from
      valve-related death at 10.8 years was 97.6 +/- 1.1% for AVR and 100% for MVR.
      Freedom from structural valve deterioration was 96.1 +/- 2.7% for AVR and 100%
      for MVR. Freedom from embolic events was 96.0 +/- 1.5% for AVR and 100% for MVR.
      In total, 16 patients needed reoperation, three for stenosis due to dystrophic
      calcification, six for endocarditis and seven for paravalvular leak. Freedom from
      reoperation was 89.9 +/- 4.2% for AVR and 80.6 +/- 7.3% for MVR. CONCLUSION:
      These results show that, over a period of up to 10 years, the Pericarbon
      pericardial bioprosthesis constitutes an excellent and safe replacement valve.

PMID- 10888102
TI  - Porcine versus pericardial bioprostheses: eleven-year follow up of a prospective
      randomized trial.
AB  - BACKGROUND AND AIM OF THE STUDY: There is renewed interest in the pericardial
      heart valve as an alternative to the porcine bioprosthesis. The long-term results
      of a randomized trial comparing a second-generation pericardial valve against a
      well-tested porcine bioprosthesis are presented. Seven-year follow up has been
      reported previously. Production of the Bioflo pericardial prosthesis used in this
      trial was discontinued due to fears related to bovine spongiform encephalopathy.
      METHODS: Between February 1987 and March 1990, 170 patients undergoing aortic
      (AVR) or mitral (MVR) valve replacement were assigned randomly to receive either
      the Bioflo pericardial bioprosthesis or the Carpentier-Edwards (CE) supra-annular
      porcine bioprosthesis. Eighty-five patients received 93 Bioflo valves (46 AVR, 31
      MVR, eight AVR+MVR), and the remaining 85 received 99 CE valves (48 AVR, 23 MVR,
      14 AVR+MVR). Mean patient age was 61.0 years (range: 38-77 years) for the Bioflo
      group and 62.1 years (range: 41-77 years) for the CE group. Current follow up is
      100% complete and totals 1,391 patient-years; mean +/- SD follow up was 8.2 +/-
      3.4 years (maximum 12.2 years). RESULTS: The operative mortality rate was 4.12%.
      There were 70 patients still at risk at 11 years (31 Bioflo, 39 CE); of these,
      91.4% were in NYHA classes I/II. No significant difference in survival or valve
      related complications was seen between the groups. Mean (+/- SEM) survival at 11
      years was 41.4 +/- 6.8% in the Bioflo group and 55.3 +/- 6.8% in the CE group (p
      = 0.15). There were 16 valve-related deaths (nine in the Bioflo group, seven in
      the CE group). At 11 years, freedom from valve-related mortality was 89.5 +/-
      3.9% for the Bioflo group and 91.0 +/- 3.5% for the CE group (p = 0.4). Valve
      position had no impact on survival. At 11 years, freedom from structural valve
      deterioration was 83.9 +/- 5.4% and 87.5 +/- 4.2% in the Bioflo and CE groups,
      respectively (p = 0.9). CONCLUSION: Over the 11-year period of follow up,
      clinical performance of the Bioflo pericardial valve was comparable with that of
      the Carpentier-Edwards supra-annular porcine bioprosthesis. No difference was
      apparent between the two valve types when implanted in either the aortic or the
      mitral position.

PMID- 10888103
TI  - A strategy for inducing immune tolerance to valve endothelial cells through gene
      transfer.
AB  - BACKGROUND AND AIM OF THE STUDY: We and others have demonstrated an immune
      response to homograft valve endothelial cells both in vivo and in vitro.
      Clinically, this is particularly manifest in children. In an attempt to address
      this problem we have explored a strategy of inducing specific immune tolerance by
      genetic manipulation of valve endothelial cells. FasL is an inducer of apoptosis;
      it binds Fas and results in programmed cell death (apoptosis) of Fas-bearing
      cells such as T lymphocytes. FasL has been shown to be important in the
      protection of tissue grafts (testis, cornea, kidney and pancreatic islet) from
      rejection. The ultimate aim of this work is to determine whether the transfection
      of FasL into human heart valve endothelial cells can hinder immune rejection by
      induction of apoptosis in T cells. METHODS: The full-length human FasL cDNA was
      cloned into a mammalian expression vector containing the neomycin resistance
      marker. The endothelial cell line HMEC-1 was transfected with the plasmid and
      selected with antibiotic G418. Cultures from positive clones were analyzed by
      semi-quantitative polymerase chain reaction (PCR) to determine approximate copy
      numbers of FasL. Reverse transcription (RT)-PCR was carried out to examine the
      production of mRNA from the construct. Western blot analysis was performed to
      detect the protein expression. Cytotoxic assays were subsequently performed to
      detect the FasL function in those transfected cells. RESULTS: High copy number
      transfected cell lines were produced, and mRNA and protein expression were
      confirmed. Preliminary results from cytotoxic assays show that transfected cells
      have enhanced cytotoxicity in comparison with their parent cell line. CONCLUSION:
      FasL can be overexpressed in endothelial cells and appears to modify the cells'
      immunological behavior. These findings could have important implications for
      enhancing homograft valve durability.

PMID- 10888104
TI  - Biaxial strain properties of elastase-digested porcine aortic valves.
AB  - BACKGROUND AND AIMS OF THE STUDY: Previous studies have suggested that elastin in
      porcine aortic valve cusps is responsible for restoring collagen fibers to their
      original configuration between loading-unloading cycles. METHODS: Biaxial loading
      tests were performed on intact aortic valves before and after elastase treatment
      to further investigate the role of elastin. RESULTS: Degradation of elastin
      caused an increase in the radial dimensions of the cusps (mean increase in gauge
      length, 29%), which corresponded to a significant decrease in radial
      extensibility (mean decrease, 61%) and a threefold increase in radial stiffness.
      Changes in circumferential extensibility and stiffness were smaller and, for most
      cusps, were not statistically significant. Control experiments, in which the
      valves were treated with buffer only, resulted in the opposite changes in radial
      dimensions and extensibility (7% decrease in gauge length and doubling of
      extensibility). CONCLUSION: Changes in the mechanical properties of the aortic
      valve cusps following incubation in elastase were due to elastin damage, and not
      incidental to soaking in buffer. As many explanted bioprosthetic valves have
      mechanical characteristics similar to those of the elastase-treated valves,
      elastin damage may be a factor in the progressive degeneration and ultimate
      failure of bioprosthetic heart valves.

PMID- 10888106
TI  - Molecular characterization of interstitial cells isolated from human heart
      valves.
AB  - BACKGROUND AND AIM OF THE STUDY: Myofibroblasts have been described as possessing
      certain characteristics of both fibroblasts and skeletal myocytes. These cells
      are of mesenchymal origin, were first described in wound healing, and have been
      found in many tissues. Myofibroblasts from other tissues have been shown to
      contract and to express sarcomeric (muscle) genes. In addition, these cells
      express certain regulatory (transcription factor) genes. The specific alignment
      of the cells may, at least in part, be governed by tissue polarity signals
      transmitted by members of the frizzled family of vertebrate tissue polarity
      genes. The aim of the present study was to characterize interstitial cells, with
      regard to the expression of myofibroblasts markers, isolated from the human heart
      valves. The expression of muscle structural, regulatory and tissue polarity genes
      has been undertaken with a view to understanding the development and contribution
      of interstitial cells to valve function and structure. METHODS: Interstitial
      cells were isolated and cultured from aortic, pulmonary, tricuspid and mitral
      valves of recipient hearts obtained during transplantation. Specific
      oligonucleotide primer pairs suitable for polymerase chain reaction (PCR) were
      designed for the genes of interest. Total RNA was extracted from the cultured
      cells and reverse transcriptase-PCR was used to determine gene expression.
      RESULTS: Cells from the four valve types were found to express various muscle
      structural genes. These include the thin filament sarcomeric genes for the
      cardiac isoforms of troponin T, I and C. Evidence was also found for expression
      of beta-myosin heavy chain (beta-MHC), alpha-MHC and cardiac myosin light chain 2
      (MLC2) in these cells. The tissue polarity genes frizzled 2 (fz2) were expressed
      in all four valve types analyzed. CONCLUSION: Interstitial cells express a number
      of genes whose products may have functional significance for heart valves. These
      include members of the contractile apparatus such as MHC and troponins. The
      presence of members of the frizzled family, which specify the orientation of cell
      polarization, in these cells could indicate that interstitial cells are not
      randomly arranged in the valve tissue. Therefore, interstitial cells isolated
      from the human heart valves express a number of functionally important genes,
      suggesting a role in their specialized function.

PMID- 10888105
TI  - Mitogenic and secretory responses of human valve interstitial cells to vasoactive
      agents.
AB  - BACKGROUND AND AIM OF THE STUDY: The vasoactive agent 5-hydroxytryptamine (5-HT)
      has been implicated in valve disease due to possible trophic effects on valve
      interstitial cells (IC). The present study was aimed at characterizing the
      responses of cultured human heart valve IC to 5-HT in terms of intracellular
      calcium concentration ([Ca2+]i), mitogenesis and collagen synthesis. The effects
      of angiotensin II (Ang II) were also studied in parallel. METHODS: IC were
      obtained by collagenase digestion of valve leaflets isolated from transplant
      recipient hearts. Changes in [Ca2+]i were measured from fluorescence of the
      ratiometric calcium dye, fura 2. Mitogenic and collagen synthetic responses of
      valve IC were measured by 3H-thymidine incorporation (DNA synthesis) and 3H
      proline incorporation assays respectively, in quiescent cells. RESULTS: Human
      valve IC responded to 5-HT and Ang II with mean maximal increases in [Ca2+]i of
      249 +/- 47 nM and 397 +/- 159 nM, respectively. 5-HT stimulated DNA synthesis in
      quiescent IC, although to varying degrees among different isolations, with a
      maximum 43.4 +/- 20.1% increase by 10(-7) M 5-HT (p <0.05). Ang II did not
      stimulate IC DNA synthesis. Valve IC also responded to 5-HT with a maximum
      increase in collagen synthesis of 15.7 +/- 2.0% by 10(-6) M 5-HT (p <0.05). Ang
      II provoked a more powerful collagen synthesis response (maximum 50.5 +/- 15.1%
      increase by 10(-5) M Ang II; p <0.05). CONCLUSION: We have shown that 5-HT and
      Ang II promote the prolonged processes of growth and collagen synthesis in
      cultured human valve IC. Thus, these vasoactive agents may play a role in the
      development of heart valve disease.

PMID- 10888107
TI  - Intermittent electromechanical dissociation due to mechanical prosthetic valve
      dysfunction.
AB  - We describe a patient who developed the rare hemodynamic phenomenon of
      intermittent electromechanical dissociation during normal sinus rhythm at about
      four months after mitral valve replacement with a Medtronic Hall prosthesis,
      along with resuspension of the papillary muscles using Gore-Tex sutures.
      Echocardiographic examination confirmed the presence of a filamentous structure
      that could be either suture material, tissue tag or thrombus, and was entangling
      intermittently in the prosthesis. The patient recovered spontaneously after a
      three-week symptomatic period, with no subsequent evidence of either
      electromechanical dissociation or the filamentous structure; normal prosthetic
      valve function was restored. During a subsequent three-month follow up period,
      the patient was asymptomatic, with normal prosthetic valve function. The
      diagnostic and hemodynamic aspects of this case are discussed.

PMID- 10888108
TI  - Atopic dermatitis as a risk factor for acute native valve endocarditis.
AB  - Colonization of Staphylococcus aureus is commonly observed in skin lesions of
      atopic dermatitis (AD) patients, and scratching of the pruritic lesions may lead
      to reiterative bacteremia. It is possible that acute native valve endocarditis
      may develop in a patient with uncontrolled AD; the latter condition may be a risk
      factor for the former. We report two cases of acute aortic and/or mitral valve
      endocarditis complicated with recurrent cutaneous infections caused by severe AD.
      The patients underwent successful surgical treatment of the heart lesions, plus
      intensive postoperative antibiotics and skin treatment for AD.

PMID- 10888109
TI  - Yukio Mitsui (1938-2000).

PMID- 10888110
TI  - Thrombopoietic activity of recombinant human interleukin-11 in nonhuman primates
      with ACNU-induced thrombocytopenia.
AB  - The effect of recombinant human interleukin-11 (rHuIL-11) on myelosuppressive
      nimustine (ACNU)-induced thrombocytopenia was assessed in nonhuman primates. A
      single intravenous (i.v.) injection of ACNU (15 mg/kg) was administered to
      cynomolgus monkeys on day 0. rHuIL-11 (100 microg/kg/day) or the vehicle was
      given subcutaneously (s.c.) from day 1 to day 21. In monkeys receiving ACNU, the
      circulating platelet count decreased to a low of 42 +/- 6 x 10(9)/L by day 21 but
      returned to pretreatment levels (375 +/- 48 x 10(9)/L) on day 30. Administration
      of rHuIL-11 prevented severe thrombocytopenia; the platelet count fell only to
      138 +/- 23 x 10(9)/L on day 18, and platelet recovery was faster (458 +/- 91 x
      10(9)/L by day 27) compared with that of the control animals. The size of bone
      marrow megakaryocytes from rHuIL-11-treated animals was larger than that of the
      controls, indicating that rHuIL-11 stimulated megakaryopoiesis in a
      myelosuppressive condition. Treatment with ACNU also caused leukopenia and
      moderate anemia. rHuIL-11 transiently and slightly decreased the white blood cell
      (WBC) and red blood cell (RBC) counts. Conversely, rHuIL-11 accelerated recovery
      of RBC count in the late administration period. These results support the
      assertion that rHuIL-11 may be an important therapeutic agent for reducing the
      severity and duration of thrombocytopenia following cancer chemotherapy.

PMID- 10888111
TI  - Altered cytokine production by specific human peripheral blood cell subsets
      immediately following space flight.
AB  - In this study, flow cytometry was used to positively identify the specific
      lymphocyte subsets exhibiting space flight-induced alterations in cytokine
      production. Whole blood samples were collected from 27 astronauts at three points
      (one preflight, two postflight) surrounding four space shuttle missions. Assays
      performed included serum/urine stress hormones, white blood cell (WBC)
      phenotyping, and intracellular cytokine production following mitogenic
      stimulation. Absolute levels of peripheral granulocytes were significantly
      elevated following space flight, but the levels of circulating lymphocytes and
      monocytes were unchanged. Lymphocyte subset analysis demonstrated a decreased
      percentage of T cells, whereas percentages of B cells and natural killer (NK)
      cells remained unchanged after flight. Nearly all the astronauts exhibited an
      increased CD4/CD8 T cell ratio. Assessment of naive (CD45RA+) vs. memory
      (CD45RO+) CD4+ T cell subsets was ambiguous, and subjects tended to group within
      specific missions. Although no significant trend was seen in absolute monocyte
      levels, a significant decrease in the percentage of the CD14+ CD16+ monocytes was
      seen following space flight in all subjects tested. T cell (CD3+) production of
      interleukin-2 (IL-2) was significantly decreased after space flight, as was IL-2
      production by both CD4+ and CD8+ T cell subsets. Production of interferon-gamma
      (IFN-gamma) was not altered by space flight for the CD8+ cell subset, but there
      was a significant decrease in IFN-gamma production for the CD4+ T cell subset.
      Serum and urine stress hormone analysis indicated significant physiologic
      stresses in astronauts following space flight. Altered peripheral leukocyte
      subsets, altered serum and urine stress hormone levels, and altered T cell
      cytokine secretion profiles were all observed postflight. In addition, there
      appeared to be differential susceptibility to space flight regarding cytokine
      secretion by T cell subsets. These alterations may be the result of either
      microgravity exposure or the physiologic stresses of landing and readaptation to
      unit gravity. Future studies, including in-flight analysis or sampling, will be
      necessary to determine the cause of these alterations.

PMID- 10888113
TI  - Differential nuclear localization of the IFNGR-1 and IFNGR-2 subunits of the IFN
      gamma receptor complex following activation by IFN-gamma.
AB  - We have recently identified a nuclear localization sequence (NLS) in the C
      terminus of murine type II interferon (IFN), IFN-gamma, that is responsible for
      the internalization and nuclear translocation of extracellularly added IFN-gamma.
      Because the uptake of IFN-gamma is a receptor-mediated endocytotic process, we
      examined in this study the fate of both the receptor subunits (IFNGR-1 and IFNGR
      2) of the heterodimeric IFN-gamma receptor complex. Human IFN-gamma (HuIFN-gamma)
      was also found to contain a polybasic NLS in a conserved C-terminal region
      capable of directing its nuclear translocation. Like the ligand, the IFNGR-1
      subunit of the receptor complex on WISH cells was found to be translocated to the
      nucleus on treatment with HuIFN-gamma. Using a combination of immunoprecipitation
      and immunofluorescence techniques, we found the nuclear accumulation of IFNGR-1
      to be ligand dependent, and it was evident within 10-20 min after ligand
      stimulation. IFNGR-1 was found to colocalize, in a time-dependent and dose
      dependent fashion, with the nuclear translocation of the transcription factor
      Stat1alpha, which is activated by this ligand-receptor system. In addition,
      Stat1alpha was found to be complexed with IFNGR-1 over the time period of its
      nuclear translocation. In marked contrast, IFNGR-2 was not transported to the
      nucleus. The surface immunofluorescence pattern of IFNGR-2 suggested that,
      following ligand stimulation, the majority of IFNGR-2 remains at the cell
      surface, whereas IFNGR-1 is endocytosed and targeted to the cell nucleus. These
      findings suggest that IFNGR-1 plays an active intracellular role in signal
      transduction events subsequent to the binding of ligand to the dimeric receptor
      complex. Furthermore, these studies provide the first example of the selective
      endocytosis and nuclear translocation of a subunit of a multimeric receptor
      complex.

PMID- 10888112
TI  - Ovine interleukin-12: analysis of biologic function and species comparison.
AB  - Interleukin-12 (IL-12) is a heterodimeric cytokine produced mainly by phagocytic
      and antigen-presenting cells (APC). The cDNA encoding the ovine IL-12 (OvIL-12)
      subunits, p40 and p35, were generated from concanavalin A (ConA)-stimulated
      peripheral blood mononuclear cells (PBMC). The ovine genes encoded proteins that
      had the highest amino acid identity to caprine p40 (99% amino acid identity) and
      p35 (97% amino acid identity) and also displayed a high degree of identity with
      human p40 (84%) and p35 (79%) homologs. To ensure the equal expression of both
      subunits, we used the self-cleaving properties of the 2A oligopeptide from foot
      and-mouth disease virus (FMDV) to express IL-12 as a single, long open reading
      frame (ORF) encoding p402Ap35. Using an in vitro transcription/translation
      system, we demonstrated that this 2A oligopeptide mediated cleavage of the
      p402Ap35 into p402A and p35, in a manner similar to the processing of the FMDV
      polypeptide. Moreover, when expressed in COSm6 cells, this self-processing
      polypeptide encoded a functional heterodimer, which elicited biologic activities
      associated with IL-12 in other species.

PMID- 10888114
TI  - Retroviral coexpression of IFN-alpha and IFN-gamma genes and inhibitory effects
      in chronic myeloid leukemia cells.
AB  - Interferon (IFN) is an effective treatment for chronic myeloid leukemia (CML) in
      chronic phases, and a number of in vitro antileukemic effects of IFN on CML cells
      have been reported. The transfer of cytokine genes into tumor cells is reportedly
      a valuable approach to improve the antitumor activity of cytokines in various
      models. We first investigated the possibility of transducing CML cells with the
      retroviral vectors LIalpha2SN and LIgammaSN, encoding the IFN-alpha2 and IFN
      gamma genes, respectively, and with the bicistronic vector LIalpha2IrIgammaSN
      coexpressing the IFN-alpha2 and IFN-gamma genes. We then analyzed the effects of
      IFN-alpha2 and IFN-gamma produced alone or simultaneously on the proliferation of
      CML cells. We optimized the transduction efficiency by using the CML-derived K562
      cell line. We then introduced IFN genes into CML CD34+ cells. Secretion of IFN
      alpha and IFN-gamma was demonstrated in K562 and CML CD34+ cells transduced with
      the different vectors. The MHC class I antigens were overexpressed in both K562
      and CML CD34+ transduced cells. Inhibition of the proliferation of
      LIalpha2IrIgammaSN-transduced CML cells was greater than with the LIalpha2SN and
      the LIgammaSN-transduced CML cells. We demonstrate an additive effect of IFN
      alpha and IFN-gamma on the inhibition of K562 and CML CD34+ cell proliferation.

PMID- 10888115
TI  - Dose-dependent and schedule-dependent effects of interleukin-12 on antigen
      specific CD8 responses.
AB  - Interleukin-12 (IL-12) has been shown to play a central role in the innate and
      acquired immune responses. Its activities include enhancement of natural killer
      (NK) and cytotoxic T lymphocyte (CTL) activity and promotion of CD4 Th1 cell
      development. It has also been shown to provide potent activity as a vaccine
      adjuvant in generating antibody and T cell responses. We have investigated the
      efficacy of IL-12 protein in promoting CD8 T cell responses when it is used as an
      adjuvant for immunization. Studies using, as antigen, cDNA from an autologous
      antigen (P1A) as well as studies of responses to vaccinia virus-delivered self
      (gp100) and non-self (beta-galactosidase) antigens show that the dose and
      schedule of IL-12 administration can significantly affect adjuvant activity,
      leading to enhancement or suppression of antigen-specific responses.

PMID- 10888116
TI  - Expression of chemokine receptors on CD4+ T cells in peripheral blood from HIV
      infected individuals in Uganda.
AB  - CXCR4, a coreceptor for T cell (T)-tropic HIV-1, is preferentially expressed on
      naive T cells, whereas CCR5, a coreceptor for macrophage (M)-tropic HIV-1, is
      preferentially expressed on previously activated memory T cells and the Th1
      subset of CD4+ T cells. CCR4 is preferentially expressed on the Th2 subset of
      CD4+ T cells. A cross-sectional flow cytometry study was conducted to evaluate
      the expression of CXCR4, CCR5, and CCR4 on the peripheral blood CD4+ T cells from
      African HIV-1-infected and uninfected Ugandan adults. The plasma viral load in
      HIV-1-infected individuals was also examined. Upregulation of CCR4 and CCR5
      expression but no decrease in CXCR4 expression on CD4+ T cells were obtained in
      peripheral blood from African adults with progression of the disease. Plasma HIV
      1 viremia significantly and inversely correlated with the peripheral CD4+ T cell
      count but did not correlate with the degree of CCR4 and CCR5 expression on the
      peripheral CD4+ T cells in HIV-1-infected individuals. Our present data suggest
      an increase in percentage of activated memory CD4+ T cells in the advanced stage
      of HIV-1 infection among African adults. There was no evidence of a Th1 to Th2
      shift in terms of chemokine receptor expression profile with advancing disease in
      the peripheral blood of these subjects.

PMID- 10888118
TI  - Three remarkable teachers.

PMID- 10888117
TI  - Rescue of human T cells by interleukin-9 (IL-9) from IL-2 deprivation-induced
      apoptosis: correlation with alpha subunit expression of the IL-9 receptor.
AB  - Interleukin-9 (IL-9) is a Th2-derived cytokine that uses the gamma-chain of the
      IL-2 receptor for signaling. Therefore, the responsiveness of human Th1 and Th2
      cell clones to IL-9 was measured by examining the ability of this cytokine to
      prevent apoptosis induced by IL-2 deprivation. A time course study demonstrated
      that both subsets of T cell clones underwent apoptosis with similar kinetics when
      deprived of IL-2 and that viability could be maintained by the addition of either
      IL-4 or IL-7. Interestingly, IL-9 prevented apoptosis in only 2 (Th2) of 14
      clones tested. Analysis of IL-9R alpha subunit expression on 18 T cell clones
      revealed that IL-9 responsiveness was directly proportional to the expression of
      the high-affinity receptor. IL-9 responsiveness was also dependent on long-term
      culturing because neither freshly isolated nor 3-day phytohemagglutinin (PHA)
      stimulated peripheral blood lymphocytes (PBL) expressed IL-9R alpha. In summary,
      the data showed that IL-9 can rescue only a small subset of Th2 cells from
      apoptosis induced by growth factor withdrawal and that expression of IL-9R alpha
      is required for the antiapoptotic signals mediated by this cytokine.

PMID- 10888119
TI  - Use of low-temperature field emission scanning electron microscopy to examine
      mites.
AB  - Partly because mites are microscopic in size and fragile in nature, acarologists
      estimate that less than five percent of extant species have been taxonomically
      described. Recently, data from conventional scanning electron microscopy (SEM)
      have been used to facilitate the descriptions and complement the information that
      has been historically obtained with the light microscope. However, the
      conventional preparation techniques associated with SEM frequently prevent or
      compromise the results. This study evaluated the use of low-temperature field
      emission SEM to image mites and their hosts. Results indicated that a modified
      cryofixation procedure, which was associated with this technique, retained the
      mites at their living/feeding sites in natural behavioral positions. Furthermore,
      the turgor of the specimens, even eggs and soft-bodied species, was also
      maintained. The structure and orientation of delicate structures such as setae,
      which would be subjected to mechanical damage during conventional chemical
      fixation, dehydration, and drying, were also preserved after cryofixation. Field
      emission SEM, which provided useful magnification beyond that attainable with a
      conventional SEM, also enabled resolution of ultrastructural features, such as
      tenent hairs on the empodium and pores on the dorsal surface that had not
      previously been observed. These advantages indicate that the low-temperature
      field emission SEM can provide important structural data that can be used to
      study the anatomy, morphology, and bioecology of mites.

PMID- 10888120
TI  - A dynamical Bragg equation for high-order Laue zone reflections
AB  - A dynamically corrected Bragg equation for high-order Laue zone (HOLZ)
      reflections is derived directly from the Bloch wave formalism instead of the
      geometric argument used to deduce the kinematical Bragg condition. It differs
      from the kinematical Bragg equation by replacing the plane wave vector in the
      kinematical equation with the Bloch wave vectors. This dynamical equation reduces
      to the kinematical equation when the crystal potential is zero. It also
      demonstrates the occurrence of dynamical shifts for the HOLZ reflections but
      their absence for the zero-order Laue zone (ZOLZ) reflections in the symmetrical
      Laue case.

PMID- 10888121
TI  - Determination of secondary electron spectra from insulators
AB  - A new technique for the determination of secondary electron (SE) spectra of
      insulators in a scanning electron microscope environment is presented. It is
      based on a capacitatively coupled charge measurement by subjecting the insulating
      film to a controlled pulsed electron beam. With the use of a planar grid analyzer
      configuration, an algorithm is used to estimate the SE spectrum based on
      normalized values of the S-curve obtained. Secondary electron spectra from
      several insulating materials employed in integrated circuit manufacturing,
      including silicon nitride (Si3N4), AZ 1350J photoresist, and pyralin polyimide,
      have been measured.

PMID- 10888122
TI  - Direct measurement of electron beam scattering in the environmental scanning
      electron microscope using phosphor imaging plates
AB  - Phosphor imaging plate technology has made it possible to directly image the
      distribution of primary beam electrons and scattered electrons in the
      environmental scanning electron microscope. The phosphor plate is exposed under
      electron scattering conditions in the microscope chamber. When processed, the
      electron intensity distribution is displayed as a digital image. The image is a
      visual representation of the electron probe and skirt and may provide the basis
      for a more accurate model.

PMID- 10888123
TI  - Lengths measurements in microvascular corrosion castings: two-dimensional versus
      three-dimensional morphometry.
AB  - In the present study we compared measurements of vessel lengths from (a) single
      digital scanning electron microscope (SEM) images of microvascular corrosion
      casts (VCCs) of gill filters of tadpoles of Xenopus laevis Daudin by two
      dimensional (2-D) morphometry (Optimas 6.5, Optimas Corp., Bothell, Wash., USA;
      planar measurements) and (b) digital stereopairs by three-dimensional (3-D)
      morphometry (3D-Morphometry, Minnich and Muska OEG, Salzburg). Depending on the
      spatial orientation of the vessels measured, we found a maximum difference of
      58.84% (100 [3-D]-41.16 [2-D]) in vessel lengths by 3-D morphometry versus 2-D
      morphometry, which, in multiple (segmental) lengths measurements or when
      determining space angles, might be even higher. Based on results we consider 3-D
      morphometry of VCCs to be the method of choice for lengths measurements.

PMID- 10888124
TI  - The reduction of the beam gas interactions in the variable pressure scanning
      electron microscope with the use of helium gas
AB  - This paper presents experimental observations on electron scattering by gases
      (helium and air) in the specimen chamber of a variable pressure scanning electron
      microscope. It shows an important reduction of the beam scattering with the use
      of helium gas, and the consequences for the x-ray microanalysis are discussed.

PMID- 10888125
TI  - Surface investigations on HgBr2 single crystals by using confocal scanning laser
      microscopy
AB  - A confocal scanning laser microscope operating at 514 and 488 nm has been used to
      obtain two-dimensional (2-D) images of the mercuric bromide (HgBr2) crystal
      surface by photoluminescence, reflection, and transmission phenomena. Our
      measurements indicate that regions showing a strong photoluminescence may appear
      on the surface. By processing the 2-D images. we obtained the three-dimensional
      images, which offer a better possibility for the investigation. The analysis of
      spectral lines may be correlated with the presence of the Hg impurities.

PMID- 10888126
TI  - "You can go forward, then...": General Stonewall Jackson and Dr. Hunter McGuire
      encounter the Federals at Chancellorsville, 1863.

PMID- 10888127
TI  - Pathologic and clinical features influencing outcome of thin cutaneous melanoma:
      correlation with newly proposed staging system.
AB  - The incidence of malignant melanoma is increasing. Because of increased
      awareness, early recognition of malignant melanoma has become more common. In
      1997, a new staging system for cutaneous melanoma was proposed, with
      reclassification of thin melanoma < 1 mm, with and without ulceration. This
      report evaluates the pathologic and clinical features of thin melanomas
      influencing recurrence and survival from a tertiary cancer center in an attempt
      to correlate findings with the proposed staging system. A review of the Roswell
      Park Cancer Institute tumor registry identified 352 patients with thin cutaneous
      melanomas (< 1.0 mm) seen during an 18-year period ending August 30, 1998.
      Overall survival was 93 and 87 per cent at 5 and 10 years, respectively. Disease
      free survival was 94 and 93 per cent at 5 and 10 years, respectively. Local
      recurrence occurred in 3 per cent of patients, regional recurrence in 3 per cent,
      and metastatic disease in 3 per cent, for an overall recurrence of 7 per cent,
      with a median follow-up of 118 months. Only the presence of ulceration was a
      significant prognostic factor for recurrence by both univariate and multivariate
      analysis. Failure rates (any recurrence) by Clark levels I, II, and III/IV were
      3, 5, and 10 per cent, respectively (P = 0.14). Failure rates by tumor thickness
      (mm), for 0.0-0.24, 0.25-0.49, 0.50-0.74, and 0.75-0.99 were 3, 4, 7, and 10 per
      cent, respectively (P = 0.49). Ten-year disease-free survival for ulceration
      versus no ulceration was 40 and 94 per cent, respectively (P < 0.0001). We
      conclude that thin cutaneous melanoma carries an excellent prognosis with
      appropriate treatment. Our findings support inclusion of ulceration in a new
      staging system. Lesions 0.76 to 0.99 mm and Clark level III and IV may warrant
      close observation as a separate subgroup.

PMID- 10888128
TI  - The effect of clinical pathway implementation on total hospital costs for
      thyroidectomy and parathyroidectomy patients.
AB  - Clinical pathways have long been used to guide the delivery of patient care in
      varied practice settings. There is little information in the literature to
      document the effectiveness of pathway implementation in general surgical
      populations. This study reports the effect of clinical pathway implementation in
      two general surgical patient groups, thyroidectomy and parathyroidectomy.
      Clinical pathways were implemented to serve patients undergoing thyroidectomy and
      parathyroidectomy surgery. The effects of both clinical pathways on total
      hospital costs, length of hospitalization, variances, and outcomes were collected
      and evaluated from July 1998 through July 1999. These data were compared to data
      from the previous year. The average length of stay for parathyroidectomy patients
      decreased from 2.4 to 1.5 days (P = 0.26) for pathway patients as compared to
      prepathway patients. The average cost per case decreased from $5071 to $4291 (P =
      0.50) for parathyroidectomy pathway versus prepathway patients. The average
      length of stay decrease for thyroidectomy patients was 1.4 to 1.2 (P = 0.16) for
      the pathway to prepathway comparison. The average cost per case decrease was
      minor at $4117 to $4111. Pharmacy costs and laboratory utilization were
      effectively reduced. Perioperative costs rose dramatically during this period,
      operating room/central sterile supply cost per case rose 12 per cent, anesthesia
      supply cost per case rose 15 per cent, and surgical pathology costs increased 110
      per cent overall for both patient groups. Clinical pathway implementation has
      allowed us to reduce or maintain total hospital costs in the face of rising
      perioperative costs. We conclude that implementation of these clinical pathways
      has allowed us to improve consistency with which we deliver care while
      maintaining the quality of patient outcomes and reducing the costs of care and
      length of hospital stay.

PMID- 10888129
TI  - Ileoanal pouch versus ileostomy: is there a difference in quality of life?
AB  - Ileoanal pouch (IAP) construction is arguably the procedure of choice to follow
      proctocolectomy for ulcerative colitis (UC) or familial adenomatous polyposis
      (FAP). Patients with UC or FAP at our institution choose their operation after
      counseling with the surgeon, with an enterostomal therapist, and with patients
      who have undergone IAP and proctocolectomy with ileostomy (IL). We studied these
      patients who chose IAP and IL, to determine differences in outcome and quality of
      life (QOL) between those two groups. We assessed outcomes by evaluating clinic
      and hospital records and surveyed patients' QOL via a standardized questionnaire.
      During a retrospective 10-year study period, 86 patients underwent evaluation for
      IAP construction for UC (64) and FAP (22). Fifty-five patients underwent IAP
      construction, and 31 underwent IL. There were no operative deaths. Thirty-four
      patients sustained 69 early and late complications (40%). The IAP group
      experienced a higher complication rate, 53 per cent, compared with the IL group,
      16 per cent. Forty-five patients (56%) have completed questionnaires. Eighty
      seven per cent of IAP patients and 93 per cent of IL patients responded that
      their overall QOL is "always" better since their operation (P = not significant).
      Both groups reported very favorable responses to questions regarding work, social
      life, family life, sleep, and relationships without statistically significant
      differences between the two groups. Despite a high complication rate, IAP is an
      excellent operation for many patients with UC or FAP, but patients who choose IL
      after preoperative counseling can be expected to have similar improvement in
      quality of life.

PMID- 10888130
TI  - Appendicitis: why so complicated? Analysis of 5755 consecutive appendectomies.
AB  - A perceived high rate of complicated (gangrenous or perforated) appendicitis,
      despite advances in laboratory and radiographic diagnostic modalities, prompted a
      review of our experience with appendicitis followed by a prospective analysis
      that examined the time course from presentation to definitive treatment in 218
      consecutive patients. In 5755 appendectomies, our overall rate of complicated
      appendicitis was 32 per cent; higher in males, in the young, and in the elderly;
      and relatively stable over each year reviewed. Prospectively, we determined that
      of the various time intervals, the time from the onset of symptoms to first
      seeking medical attention is the only significant predictor of complicated
      appendicitis (39.8 vs 16.5 hours for acute appendicitis). On the other hand, the
      time from surgical evaluation to operative intervention was significantly shorter
      for complicated appendicitis (3.8 vs 4.7 hours for acute appendicitis). The high
      rate of complicated appendicitis with its subsequent sequelae of increased
      morbidity and resource expenditure is primarily the direct result of patient
      delay in seeking medical attention and not the result of diagnostic dilemma or
      surgical delay. Public education, specifically targeting those groups at risk,
      may provide a substantial and significant solution to the complicated appendix.

PMID- 10888131
TI  - Appendicitis in pregnancy.
AB  - Appendicitis continues to be the most common nonobstetric surgical diagnosis in
      pregnancy. Historically, this diagnosis has been associated with an increased
      risk of fetal loss as well as maternal morbidity. The physiologic and anatomic
      changes in pregnancy have been thought to obscure and thus delay the diagnosis of
      acute appendicitis, contributing to its increased risk in pregnancy. Such
      increased risks have been well reported in literature. To further evaluate the
      overall incidence, to determine the factors contributing to delay in diagnosis,
      and to assess overall outcomes in appendicitis in pregnancy, we performed a
      retrospective contemporary evaluation of pregnant patients with the diagnosis of
      acute appendicitis during the period 1991-1998. Twenty-two patients had the
      combined admitting diagnoses of pregnancy and acute appendicitis among 44,845
      deliveries for the same time period (incidence, 0.05%). Gestational stage at
      diagnosis was the first trimester in 5 patients (22%), second trimester in 6
      patients (27%), and third trimester in 11 patients (50%). Nineteen patients (86%)
      had pathologically proven acute appendicitis. Sixteen patients (73%) presented
      with less than 24 hours of abdominal symptoms. Seventeen patients (77%) presented
      with findings of rebound and guarding on initial physical examination. Fifteen
      patients (68%) were taken to the operating room within 24 hours of presentation.
      Of these, 10 patients (68%) had acute perforated appendicitis. Overall, there
      were 12 cases of perforated appendicitis (55%), which is an incidence higher than
      what has been reported in literature. There were no instances of fetal mortality.
      Preterm labor occurred in 5 patients, all in their third trimester with
      perforated appendicitis. Our study found that our population paralleled the
      incidence of gestational appendicitis of 0.05-0.07 per cent; physical examination
      on presentation was the most reliable diagnostic tool for appendicitis; and there
      is a higher incidence of perforation with increased gestational age, which does
      not result in increased fetal mortality.

PMID- 10888132
TI  - Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for
      disseminated peritoneal cancer of gastrointestinal origin.
AB  - No standard effective treatment exists for peritoneal carcinomatosis of
      gastrointestinal origin. The pharmacokinetic advantage of intraperitoneal
      chemotherapy and the synergy of heat and certain anticancer agents have prompted
      researchers to investigate intraperitoneal hyperthermic chemotherapy in treating
      disseminated peritoneal cancers. We have conducted a large Phase II trial to
      determine the safety and efficacy of aggressive cytoreductive surgery and
      intraperitoneal hyperthermic chemotherapy (IPHC) in treating peritoneal
      carcinomatosis of gastrointestinal origin. Patients with disseminated peritoneal
      carcinomatosis of gastrointestinal origin with or without malignant ascites were
      eligible. After aggressive surgical debulking, patients were administered a 2
      hour heated (40.5 degrees C) intraperitoneal perfusion with mitomycin C. The
      major response variable monitored was overall survival. Patients were assessed
      for toxicity after IPHC administration using the National Cancer Institute Common
      Toxicity Criteria. Eighty-four patients with peritoneal carcinomatosis of
      gastrointestinal origin were evaluated for survival and toxicity (colon, n = 38;
      appendix, n = 22; stomach, n = 19; other gastrointestinal, n = 5). Thirty-nine
      (46%) patients had malignant ascites at the time of therapy. The operative
      mortality (30-day) was 6 per cent. Hematologic toxicity was the most common
      toxicity but was of mild to moderate severity (7 and 4% of patients had grade 3/4
      white blood cell or platelet toxicity, respectively). The overall median survival
      was 14.3 months. The median survival of patients with peritoneal carcinomatosis
      of appendiceal, colorectal, and gastric origins were 31.1+, 14.6, and 10.1
      months, respectively. Significant differences in median survival were seen in
      patients without and with malignant ascites (27.7 vs 7.6 months; P = 0.0004) and
      R0/R1 (complete gross tumor resection) versus R2 (gross residual tumor) surgical
      resection status (28.5+ vs 10.8 months, P = 0.0002). These data suggest that
      aggressive cytoreductive surgery with IPHC using mitomycin C is safe and
      effective in treating peritoneal carcinomatosis of gastrointestinal origin.
      Additional studies and broader applications of this treatment are encouraged.

PMID- 10888133
TI  - Video-assisted thoracoscopic surgery for children with stage II empyema.
AB  - Children with stage II empyema often fail traditional medical management,
      frequently succumbing to the effective albeit morbid clutches of thoracotomy.
      Video-assisted thoracoscopic surgery (VATS) has been recently introduced as a
      viable and potentially less morbid alternative to open thoracotomy. We review our
      VATS experience in children with empyema, assessing surgical outcome. Between
      August 1996 and March 1999, 13 patients at our institution with stage II empyema
      that did not respond to conventional medical management underwent a modified VATS
      with decortication. Data from retrospective chart review reflects intraoperative
      findings and postoperative course, including average time to defervescence,
      removal of thoracostomy tube, and hospital discharge. VATS was completed in all
      13 patients. All intraoperative cultures of pleural fluid and fibrinopurulent
      debris obtained at VATS showed no growth. The average time to defervescence was
      2.2 days (range, 0-4 days) and to removal of thoracostomy tube 3.6 days (range, 2
      5 days). Average total chest tube days in patients with pre-VATS thoracostomy (n
      = 6) was 14.5 days (range, 8-37 days) versus 3.1 days (range, 2-5 days) in
      patients (n = 7) who underwent primary VATS (t test, p < 0.05). The average time
      to surgical discharge after VATS was 5.8 days (range, 3 to 19 days). All patients
      were well on follow-up clinic visits without delayed complications. VATS can be
      performed safely and effectively in children with stage II empyema, thus avoiding
      the morbidity of open thoracotomy and decortication. Importantly, early
      application of VATS significantly relieves patients of unnecessary days of
      thoracostomy drainage.

PMID- 10888134
TI  - Do cytokeratin-positive-only sentinel lymph nodes warrant complete axillary lymph
      node dissection in patients with invasive breast cancer?
AB  - The small number of nodes harvested with lymphatic mapping and sentinel lymph
      node (SLN) biopsy has allowed a more detailed pathologic examination of those
      nodes. Immunohistochemical stains for cytokeratin (CK-IHC) have been used in an
      attempt to minimize the false negative rate for SLN mapping. This study examines
      the value of CK-IHC positivity in predicting further lymph node involvement in
      the axillary basin. From April 1998 through May 1999, 519 lymphatic mappings and
      SLN biopsies were performed for invasive breast cancer. SLNs were examined by
      imprint cytology, hematoxylin and eosin (H&E), and CK-IHC. Patients with evidence
      of metastatic disease by any of the above techniques were eligible for complete
      axillary node dissection (CAND). The frequency with which these modalities
      predicted further lymph node involvement in the axillary basin was compared. Of
      the 519 lymphatic mappings, 39 patients (7.5%) had a CK-IHC-positive-only SLN.
      Five (12.8%) of these 39 patients had at least 2 SLNs positive by CK-IHC. Twenty
      six of the CK-IHC-positive-only patients underwent CAND. Three of these 26
      patients (11.5%) had additional metastases identified after CAND. The sensitivity
      levels with which each modality detected further axillary lymph node involvement
      were as follows: CK-IHC, 98 per cent; H&E, 94 per cent; and imprint cytology, 87
      per cent. A logistic regression to compare the prognostic value of the three
      modalities was performed. All were significant, with odds ratios of 19.1 for CK
      IHC (P = 0.015), 5.3 for H&E (P = 0.033), and 3.86 for imprint cytology (P =
      0.0059). These data validate the enhanced detection of CK-IHC for the evaluation
      of SLNs. Detection of CK-IHC-positive SLNs appears to warrant CAND in patients
      with invasive breast cancer. However, the therapeutic value of CAND or adjuvant
      therapies based on CK-IHC-positive SLNs would be best answered by prospective
      randomized trials.

PMID- 10888135
TI  - Cost savings associated with changes in routine laboratory tests ordered for
      victims of trauma.
AB  - Not all trauma victims evaluated by the trauma service require a full complement
      of laboratory tests upon admission. This study set out to determine the cost
      savings and safety of limited laboratory testing of trauma victims. Before 1998,
      our admission trauma protocol included 11 laboratory tests for all trauma
      victims. In 1998, we created two categories: Trauma Blue--severe injury likely
      (Glasgow Coma Score <13; systolic blood pressure <100 mm Hg at any time;
      significant head, chest, abdominal, or proximal long bone injury; or clinical
      suspicion of need for operative or intensive care unit management) and Trauma
      Yellow--severe injury unlikely. The triage decision was made by the team leader
      or attending physician. Trauma Blue laboratory tests included an arterial blood
      gas, blood alcohol, type and screen or crossmatch, and urine dipstick. All
      patients who did not meet Trauma Blue criteria were entered in the Trauma Yellow
      group. There were only two tests for the Trauma Yellow group, a venous blood gas
      and blood alcohol. All arterial and venous blood gases measured pH, pO2, pCO2,
      HCO3, base deficit, hemoglobin, sodium, potassium, and ionized calcium. Other
      laboratory tests were done if requested by the trauma team leader or attending
      physician. All trauma admissions for a 3-month period were entered into this
      prospective study. The admitting trauma surgeon was surveyed after each admission
      to evaluate any problems in patient care. The test group was compared with a
      historical control of 100 consecutive patients under the original laboratory
      trauma protocol. One hundred and forty-eight (148) patients were entered into the
      study. Average laboratory cost per patient was $29.82 less with the study
      protocol. No patient care problem was identified. A cost savings of $29.82 per
      patient or $20,000.00 a year was realized for our institution, with no change in
      the quality of patient care. Trauma protocols designed to reflect a patient's
      potential for serious injury can result in a significant cost savings while
      preserving patient safety.

PMID- 10888136
TI  - A structured curriculum for improved resident education in statistics.
AB  - Many resident physicians do not receive sufficient education in statistical
      theory and study design to allow them to effectively interpret and apply the
      medical literature to patient care. A survey of 62 surgical residency programs
      identified that only 33 per cent include formal statistics teaching in their
      curricula. A structured curriculum was formulated to introduce surgical residents
      to basic statistical theory, common statistical tests, and study design. Lectures
      were integrated into an existing monthly journal club in which manuscripts
      reviewed were used to illustrate the statistical concepts taught. Knowledge
      improvement was determined using a multiple choice test given before and after
      completion of the curriculum. Mean test scores increased significantly as a
      result of the curriculum (P < 0.004). Formal statistics education using a
      structured curriculum significantly improves resident physician knowledge of
      statistical theory and study design. Such teaching can be easily integrated into
      a residency program's existing curriculum.

PMID- 10888137
TI  - Appendicitis due to bird shot ingestion: a case study.
AB  - Appendicitis due to foreign bodies is rare. Foreign bodies leading to
      appendicitis or perforation are usually sharp, pointed objects. Lead shot can
      become lodged in the appendix. Few prior cases have shown a causal relationship
      between the presence of pellets in the appendix and acute appendicitis. We
      present the case of a 9-year-old white boy who presented to the emergency room
      with a 36-hour history of right lower quadrant pain over McBurney's point
      accompanied by anorexia. The patient's history was significant for consumption of
      pheasant meat 4 days before onset of symptoms. The pheasant had been shot with a
      shotgun. X-ray of the child's abdomen revealed a metallic foreign body in the
      right lower quadrant. Appendectomy was performed. Bird shot was found obstructing
      the lumen of the grossly inflamed appendix. Pathology was consistent with acute
      appendicitis. This case is presented as an interesting consequence of bird shot
      ingestion.

PMID- 10888138
TI  - Is total colonic evaluation for anal cancer necessary?
AB  - The purpose of this study was to evaluate the necessity of total colonic
      evaluation in patients diagnosed with anal cancer. We reviewed the cases of 69
      patients treated for neoplasm of the anus from January 1973 through November
      1998. Patients underwent a barium enema, flexible sigmoidoscopy or colonoscopy;
      findings from these procedures were analyzed. Anal pathology included: squamous
      cell carcinoma, 48 patients (72%); adenocarcinoma, 6 patients (9%); and squamous
      cell carcinoma in situ, 10 patients (15%). Chemoradiation was completed in 41
      patients (61%), and 6 patients (9%) underwent abdominal perineal resection. Wide
      excision was the primary therapy in 15 patients (22%). Procedures included:
      colonoscopy, 31 patients (46%); flexible sigmoidoscopy only, 15 patients (22%);
      barium enema only, 3 patients (5%); and a combination of flexible sigmoidoscopy
      and barium enema, 18 patients (27%). Eighty-five per cent of patients had a
      normal colonic evaluation. Ten patients (15%) had single or multiple polyps
      identified. Six adenomatous polyps and two hyperplastic polyps were found. No
      synchronous colorectal malignancy was identified. We conclude that colonoscopy is
      an integral part of colonic surveillance in patients diagnosed with anal
      carcinoma, but our study fails to find evidence to support such intervention. The
      standard screening recommendation for colorectal cancer based on age and risk
      factors is appropriate intervention for patients diagnosed with anal cancer; anal
      cancer itself does not appear to be one of these risk factors.

PMID- 10888139
TI  - Intraoperative monitoring of recurrent laryngeal nerve function.
AB  - Intraoperative recurrent laryngeal nerve identification is sometimes difficult in
      reoperative cervical dissection or operation for inflammatory thyroid disorders.
      Three modalities have been described to intraoperatively assess nerve function:
      vocal cord visualization with fiberoptic bronchoscopy or direct laryngoscopy,
      electromyelographic surveillance of arytenoid muscle function, and cord function
      assessment with an electromyelogram-electrode endotracheal tube. Our study
      focused on patients requiring cervical dissection for thyroid or parathyroid
      disease in which intraoperative recurrent laryngeal nerve function was monitored
      by nerve stimulation with a concentric bipolar probe. Impulses were tracked via a
      specialized electrode-bearing endotracheal tube with signal transduction to a
      recording monitor. No operative nerve injuries occurred in the patients of our
      study group. This surveillance technique's several advantages include use of
      standard intubation techniques with no increase in operative time, nerve
      stimulation tracings that are quantifiable and reproducible with production of a
      permanent record, and less subjectivity due to observer variability. We believe
      these factors make the electromyelogram-electrode endotracheal tube approach to
      intraoperative recurrent laryngeal nerve assessment the optimal technique.

PMID- 10888140
TI  - Do patients with acute deep vein thrombosis have fever?
AB  - The purpose of this study was to determine whether those with lower extremity
      acute venous thrombosis have fever. During a recent 14.5-month period, 1847
      patients undergoing lower extremity venous duplex scanning also had their oral
      temperature measured using a digital thermometer at the time of duplex
      examination. Patients were 57.8 +/- 17.3 years of age (range, 14 to 99).
      Temperature was 98.5 +/- 1.1 degrees F. Twenty-three patients had acute inferior
      vena cava thrombosis, 60 had acute iliac vein thrombosis, 138 had acute femoral
      venous thrombosis, and 131 had acute popliteal venous thrombosis. Calf vein
      thromboses were present in 102 patients, and 43 patients had superficial venous
      thrombosis. A total of 228 patients had acute lower extremity venous thrombosis
      in one or more of these venous segments. Temperature with acute lower extremity
      venous thrombosis was 98.7 +/- 1.05 degrees F versus 98.5 +/- 1.10 degrees F in
      those with no acute thrombosis. Although small, this temperature difference was
      statistically significant (P < 0.02). Acute deep venous thrombosis (DVT) was
      defined as acute popliteal or more proximal femoral, iliac, or vena cava
      thrombosis. The temperature for the 175 patients with acute DVT was 98.7 +/- 1.10
      degrees F versus 98.5 +/- 1.10 degrees F for those without DVT (P < or = 0.035).
      There was no temperature that served to accurately differentiate those who did
      from those who did not have DVT. The frequency that patients with DVT had fever,
      defined as a temperature > or = 100 degrees F, was 9.1 per cent (16 of 175) with
      DVT versus 7.5 per cent (126 of 1678) without DVT (not significant). In the
      subgroup with a temperature > or = 101 degrees F, 4.6 per cent (8 of 175) with
      DVT had such a fever versus 3.4 per cent (57 of 1672) without DVT (not
      significant). Those undergoing venous duplex who were found to have acute lower
      extremity venous thrombosis, including acute DVT, had statistically higher
      temperatures, but such temperature differences were minimal. The incidence of
      fever, defined as a temperature > or = 100 degrees F or > or = 101 degrees F, was
      not different between those with and those without acute DVT. It appears that the
      presence of fever may not be a sensitive or specific indicator for the presence
      of underlying acute DVT.

PMID- 10888141
TI  - Herniation of the hepatic flexure through the foramen of Winslow: a case report.
AB  - Herniation through the foramen of Winslow is among the rarest of internal
      hernias. Predisposing factors include an enlarged epiploic foramen, a mobile
      cecum and ascending colon, and an abnormal length of small bowel mesentery.
      Obstruction, strangulation, and perforation with associated metabolic and septic
      sequelae are the major complications associated with this disease. We report a
      case of herniation through the foramen of Winslow in which the diagnosis was
      established preoperatively.

PMID- 10888142
TI  - A trauma systems assessment of boating safety: a comparison of commercial and
      recreational boating practices.
AB  - OBJECTIVE: With contemporary interest of Trauma Systems and injury prevention
      strategists focusing upon boating safety, a prospective study was designed to
      survey practices of commercial and recreational boaters' compliance with United
      States Coast Guard (USCG) regulations. Data were collected by interview survey.
      Information was obtained from 24 commercial and 57 recreational boaters.
      Prevalence rates were calculated for compliance with USCG regulations. An
      analysis for statistical difference was conducted using the Wilcoxon rank sum
      test. Data analysis revealed that commercial boaters statistically spend more
      days on the water per year and have more years of boating experience than do
      recreational boaters (P < 0.05). No statistical difference was demonstrated
      between commercial and recreational boaters for life jacket-to-crew member ratio,
      swimming competency, or compliance with USCG safety equipment, with exception to
      flotation suits. The prevalence of alcohol use by the operators of commercial and
      recreational boats was found to be 8 and 12 per cent (P < 0.60) respectively, and
      for crew members 8 and 35 per cent (P < 0.01), respectively. Boating practices in
      these sample populations conform to USCG regulations. Swimming competency
      exhibited by these boaters is complementary to safe boating behaviors. The
      consumption of alcohol while boating, although comparable to reported statistics,
      is still of concern to injury prevention strategists.

PMID- 10888143
TI  - Galen's life and contributions.

PMID- 10888144
TI  - To work: perchance to sleep.

PMID- 10888145
TI  - Treatment of trauma-associated hypothermia in children: evidence-based practice.
AB  - BACKGROUND: Hypothermia is a serious immediate consequence of traumatic injury in
      children. Although numerous studies have addressed the treatment of hypothermia
      in adults after trauma or surgery, few have examined this issue in injured
      children. OBJECTIVES: To evaluate the research literature on when and how to
      treat hypothermia during emergency care of children with trauma and to apply
      these findings to clinical nursing practice. METHODS: Electronic literature
      searches conducted periodically for 3 years yielded more than 50 publications on
      hypothermia and its treatment in trauma and surgical patients. Publications were
      grouped by cause of hypothermia and by warming methods. Single case reports and
      publications related to submersion injuries were excluded. RESULTS: Three
      clinical trials of patients with head injuries included adolescents aged 15 years
      and older. One study compared peripheral and core warming methods used during
      operative management of infants and young children. Only one study evaluated core
      warming in children with trauma. DISCUSSION: The treatments examined in the few
      research-based studies on the treatment of hypothermia during emergency care of
      children with trauma were given low recommendations. Although the warming methods
      were successful in selected surgical and adult patients, the methods cannot be
      recommended for treating children with trauma because of the lack of evidence
      based findings. CONCLUSIONS: Caution should be used when extrapolating published
      data on the treatment of hypothermia in injured adults to injured children.
      Ongoing clinical trials should evaluate in children with trauma those warming
      methods that have been used successfully in surgical patients.

PMID- 10888146
TI  - Differences between blacks and whites with coronary heart disease in initial
      symptoms and in delay in seeking care.
AB  - BACKGROUND: Mortality rates for coronary heart disease are higher in blacks than
      in whites. OBJECTIVES: To examine differences between blacks and whites in the
      manifestation of symptoms of coronary heart disease and in delay in seeking
      treatment. METHODS: Patients were directly observed as they came to an emergency
      department with symptoms suggestive of coronary heart disease. The sample
      included 40 blacks and 191 whites with a final diagnosis of angina or acute
      myocardial infarction. RESULTS: After controlling for pertinent demographic and
      clinical characteristics, logistic regression analysis revealed that blacks were
      more likely than whites to have shortness of breath (odds ratio = 3.16; 95% CI =
      1.49-6.71; P = .003) and left-sided chest pain (odds ratio = 2.55; 95% CI = 1.10
      5.91; P =.03). Blacks delayed a mean of 26.8 hours (SD = 30.3; median = 11
      hours), whereas whites delayed a mean of 24.4 hours (SD = 41.7; median = 5 hours)
      in seeking care. Mean delay time was not significantly different for blacks and
      whites; differences in median delay time were of borderline significance (P =
      .05). CONCLUSIONS: Blacks were more likely than whites to have shortness of
      breath and left-sided chest pain as the presenting symptoms of coronary heart
      disease. Differences in delay in seeking treatment were not significant, although
      blacks tended to delay longer than did whites. The relatively small number of
      blacks may account for the lack of observed racial differences in both initial
      symptoms and in delay in seeking treatment.

PMID- 10888147
TI  - Differences between men and women in anxiety early after acute myocardial
      infarction.
AB  - BACKGROUND: Anxiety after acute myocardial infarction influences both short- and
      long-term recovery. Therefore, determining specific subgroups of patients who
      have relatively higher anxiety levels is important. Published findings about
      gender differences in anxiety after acute myocardial infarction are conflicting.
      OBJECTIVES: To determine whether gender differences in anxiety after acute
      myocardial infarction exist and whether any of the sociodemographic and clinical
      variables that often differ between men and women with acute myocardial
      infarction interact with gender to influence anxiety. METHODS: A total of 424
      patients with confirmed acute myocardial infarction were enrolled in this
      multicenter prospective study. Patients' anxiety level was measured within 72
      hours of their arrival at the hospital by using the State Anxiety Inventory and
      the Brief Symptom Inventory. RESULTS: Women had significantly higher anxiety than
      did men according to both the State Anxiety Inventory (42 +/- 12.9 vs 37.7 +/-
      12.5; P = .001) and the Brief Symptom Inventory (0.83 +/- 0.97 vs 0.63 +/- 0.71;
      P = .02). Of the sociodemographic and clinical variables examined, only marital
      status and income significantly interacted with gender to influence anxiety.
      Married women had higher anxiety than did single and widowed women, and married
      men had lower anxiety than did single men. Women with lower income had higher
      anxiety than did women with higher income; income was not related to anxiety in
      men. CONCLUSION: Women report significantly greater anxiety early after acute
      myocardial infarction than men do. Women's greater anxiety may be partially
      explained by marital status and lower income at the time of the infarction.

PMID- 10888148
TI  - Temperature measurement in critically ill adults: a comparison of tympanic and
      oral methods.
AB  - BACKGROUND: Despite increasing use of tympanic thermometers in critically ill
      patients who do not have a pulmonary artery catheter in place, variations in
      measurements obtained with the thermometers are still a problem. OBJECTIVE: To
      compare the range of variability between tympanic and oral electronic
      thermometers. METHODS: Subjects were a convenience sample of 72 patients admitted
      to a 24-bed adult medical-surgical intensive care unit. For each patient,
      temperatures were measured concurrently (within a 1-minute period) with an oral
      (Sure Temp 678) thermometer, a pulmonary artery catheter (Baxter VIP Swan-Ganz
      Catheter), and 2 tympanic (FirstTemp Genius II and ThermoScan Ear Pro-1)
      thermometers. Each subject was used up to 3 times for data collection.
      Measurements obtained with the oral and tympanic thermometers were compared with
      those obtained with the pulmonary artery catheter. Nonparametric analysis of data
      was used. RESULTS: The magnitude of error for the ThermoScan tympanic thermometer
      differed significantly from that of the Genius II tympanic thermometer and the
      SureTemp oral thermometer (P < .001). Application of the Bland and Altman method
      to frame the data on the basis of an accuracy tolerance zone of +/-0.5 degrees C
      indicated variability with both the oral and tympanic methods. The overall degree
      of variability was lower for the oral thermometer. CONCLUSIONS: Oral thermometers
      provide less variable measurements than do tympanic thermometers. Use of oral
      thermometry is recommended as the best practice method for temperature evaluation
      in critical care patients when measurement of core temperature via a pulmonary
      artery catheter is not possible.

PMID- 10888150
TI  - Heparin-induced thrombocytopenia and thrombosis syndrome after cardiopulmonary
      bypass.

PMID- 10888149
TI  - Effect of the 30 degree lateral recumbent position on pulmonary artery and
      pulmonary artery wedge pressures in critically ill adult cardiac surgery
      patients.
AB  - BACKGROUND: Despite demonstrated benefits of lateral positioning, critically ill
      patients may require prolonged supine positioning to obtain reproducible
      hemodynamic measurements. OBJECTIVES: TO determine the effect of 30 degree right
      and left lateral positions on pulmonary artery and pulmonary artery wedge
      pressures after cardiac surgery in critically ill adult patients. METHODS: An
      experimental repeated-measures design was used to study 35 patients with stable
      hemodynamics after cardiac surgery. Subjects were randomly assigned to 1 of 2
      position sequences. Pulmonary artery and pulmonary artery wedge pressures were
      measured in each position. RESULTS: Measurements obtained from patients in the 30
      degree left lateral position differed significantly (all Ps < .05) from
      measurements obtained from patients in the supine position for pulmonary artery
      systolic, end-diastolic, and mean pressures. Pulmonary artery wedge pressures did
      not differ significantly; however, data were available from only 17 subjects. The
      largest mean difference in pressures between the 2 positions was 2.0 +/- 2.1 mm
      Hg for pulmonary artery systolic pressures, whereas maximum differences for end
      diastolic and pulmonary artery wedge pressures were 1.4 +/- 2.7 mm Hg and 1.6 +/-
      2.4 mm Hg, respectively. Clinically significant position-related changes in
      pressure occurred in 12 (2.1%) of 581 pressure pairs. Clinically significant
      changes occurred in end-diastolic pressure in 2 subjects and in pulmonary artery
      wedge pressure in 1 subject. CONCLUSIONS: In patients with stable hemodynamics
      during the first 12 to 24 hours after cardiac surgery, measurements of pulmonary
      artery and pulmonary artery wedge pressures obtained in the 30 degree lateral and
      supine positions are clinically interchangeable.

PMID- 10888151
TI  - Variables influencing patients' outcomes after elective aortic reconstruction
      surgery.
AB  - BACKGROUND: Aortic reconstruction surgery for aneurysmal and occlusive disease is
      associated with significant morbidity and mortality. OBJECTIVES: To determine
      what variables influence patients' outcomes after elective aortic reconstruction
      surgery so that an evidence-based best-practice initiative can be developed for
      these patients. METHODS: A descriptive, comparative study of all patients
      undergoing elective aortic reconstruction from October 1997 through December 1998
      was used. Retrospective chart review was used to collect demographic and clinical
      data on the first 48 subjects, who had been discharged from the hospital. Data on
      the other 63 subjects were collected prospectively. RESULTS: The typical subject
      was a 65-year-old man with a history of cardiovascular disease, hypertension, and
      smoking. Subjects were grouped by type of surgery and by outcome (survived
      without complications vs died or survived with major complications). Outcomes
      were not significantly different in patients undergoing different types of
      surgery. Variables associated with poor outcomes included history of
      cardiovascular disease, elevated preoperative levels of serum urea nitrogen and
      creatinine, high volumes of salvaged autologous blood administered
      intraoperatively, and early postoperative hypotension that required treatment.
      Pulmonary complications were the most common; next most common were cardiac
      complications. History of cardiovascular disease and hypotension were significant
      predictors of outcome. CONCLUSION: The variables associated with poor outcomes
      can be used to design a best-practice initiative for patients undergoing elective
      aortic reconstruction.

PMID- 10888152
TI  - A novel device in evaluating syncope.
AB  - Syncope may be a manifestation of many diseases. The etiology is often difficult
      to determine. Much effort, time, and expense have been required to determine a
      diagnosis. A thorough history and physical examination are essential (Table 3).
      Several clinical pearls may be of help in the diagnosis of syncope: (a) the most
      important elements in the evaluation of syncope are a detailed history and
      physical examination; (b) syncope is a common problem in young healthy adults and
      the elderly; (c) a heavy meal is a specific cause of syncopy in the elderly
      (postprandial), however this etiology often goes unrecognized; (d) syncope is
      caused by 1 of 3 mechanisms: decreased cardiac output, systemic vascular
      resistance, or cerebrovascular disease; (e) reflex-mediated syndromes (vasovagal)
      are common causes of syncope in young adults, and orthostatic hypotension is an
      important cause of syncope in the elderly; and (f) the 1-year mortality of
      cardiac syncope (18%-33%) is significantly higher than that from non-cardiac
      syncope (0%-12%). A proven and useful tool has recently been advanced to aid in
      the evaluation of syncope. The Reveal Plus insertable loop recorder has auto
      activation that allows automatic capture and recording of arrhythmic events.
      Patient activation is an option. The recorder lasts 12 to 14 months and has
      proven to be a valuable and reliable cost-effective asset in our quest to
      evaluate syncope.

PMID- 10888153
TI  - Reliability of pulmonary artery pressure (PAP) measurements.

PMID- 10888154
TI  - Young adults seriously injured in alcohol-related motor vehicle crashes.

PMID- 10888155
TI  - Prone positioning of patients with acute respiratory distress syndrome.

PMID- 10888156
TI  - Reimbursement for acute care nurse practitioner services.

PMID- 10888157
TI  - Pressure ulcers add to morbidity and human misery.

PMID- 10888158
TI  - Hemiarthroplasty for cuff tear arthropathy.
AB  - A retrospective review was conducted on 15 cases of shoulder hemiarthroplasty
      performed for cuff tear arthropathy. All cases had advanced glenohumeral
      arthritis with complete supraspinatus and infraspinatus rupture and substantial
      involvement of the teres minor and subscapularis. The mean patient age was 73
      years; the mean follow-up was 28.2 months. Range of motion, functional ability,
      pain relief, and overall patient satisfaction were assessed preoperatively and
      postoperatively. The average active forward elevation increased from 69 degrees
      to 86 degrees, and the average active external rotation increased from 15 degrees
      to 29 degrees. Thirteen patients had an increase in their ability to perform
      activities of daily living, 1 patient was unchanged, and 1 patient had a decrease
      in ability to perform activities of daily living. Pain relief was significantly
      improved in all but 1 patient. Eleven patients (13 of 15 shoulders, 87%)
      expressed an overall satisfaction with their surgery. Patients were assessed
      preoperatively and postoperatively through use of the UCLA Rating Scale; the
      average increase was 11 to 22 points. In addition, isokinetic strength testing
      was performed preoperatively and postoperatively on 6 of the 15 involved
      shoulders. An increase in peak torque in forward elevation, abduction, and
      external rotation was noted postoperatively. The findings of this study indicate
      that favorable clinical results can be obtained after hemiarthroplasty of the
      shoulder with associated massive rotator cuff deficiency.

PMID- 10888159
TI  - Shoulder pathology associated with symptomatic acromioclavicular joint
      degeneration.
AB  - We report the incidence and nature of shoulder disease found in association with
      symptomatic degenerative change in the acromioclavicular joint in 218 shoulders.
      Coexisting pathologic conditions were present in 213 shoulders: rotator cuff
      degeneration in 176 shoulders (79 with complete thickness tears), labral tears in
      72, glenohumeral degeneration in 31, and biceps tendon disease in 49. In 59
      shoulders findings were unexpected. We looked specifically at 2 age groups: <50
      years and > or =50 years. In the <50 years group labral tears were seen in 42%
      (30 of 71) and rotator cuff disease in 65% (46 of 71). Cuff tears tended to be
      incomplete. In the older age group only 14% (21 of 147) had an intact cuff, with
      72 shoulders having a full-thickness tear. Labral tears were seen in 29% (42 of
      147). We recommend that all patients undergo shoulder arthroscopy at the time of
      acromioclavicular surgery.

PMID- 10888160
TI  - Osteonecrosis of the humeral head: results of replacement.
AB  - One hundred twenty-seven shoulders treated with replacement arthroplasty for
      osteonecrosis of the humeral head were reviewed and assessed by mailed
      questionnaire for results, durability, and complications. These included 71
      humeral head replacements and 56 total shoulder replacements. Thirty-six
      shoulders were lost to follow-up because of death of the patient; an additional 3
      shoulders were locking survey follow-up. Thus current follow-up was available for
      88 shoulders. At an average follow-up of 8.9 years, subjective improvement was
      expressed for 70 (79.5%) of the shoulders and no to occasional moderate pain for
      68 (77.3%). The mean American Shoulder and Elbow Surgeon score was 63, and the
      median was 68. Inferior results in American Shoulder and Elbow Surgeon score and
      range of motion were noted in post-traumatic osteonecrosis, and superior results
      were noted in steroid-induced osteonecrosis. Little difference was found between
      humeral head replacement and total shoulder replacement. The most common
      postoperative complication was rotator cuff tearing, found in 23 (18.1%) of 127
      shoulders. This complication was more common in shoulders with a history of any
      surgery. The cause of osteonecrosis and previous treatment have important
      implications for the results of shoulder replacement for this disease.

PMID- 10888161
TI  - Subacromial space in the rheumatoid shoulder: a radiographic 15-year follow-up
      study of 148 shoulders.
AB  - A cohort of 74 patients with rheumatoid arthritis was monitored prospectively for
      15 years. At the end of the study 148 shoulders were radiographed with a standard
      method. The subacromial space was examined from the radiographs with a method
      where the acromiohumeral interval was measured from the dense cortical bone
      marking the inferior aspect of the acromion to a point directly above the head of
      the humerus. The smallest distance was recorded, and negative values were used
      when the original articular surface of the humerus exceeded the inferior surface
      of the acromion. Destruction of the glenohumeral (GH) joints was assessed by the
      Larsen method on a scale of 0 to 5. The relation of subacromial space measurement
      to the grade of destruction of GH joints was examined. The mean subacromial space
      was 6.7 (SD 4.4), range from -13 to 12 mm: 6.1 mm (SD 5.6) in men and 6.9 mm (SD
      4.0) in women. The mean of nonaffected (Larsen grade 0 or 1) shoulders (n = 77)
      was 8.6 mm (SD 1.5), and the corresponding mean of the affected (Larsen grade >
      or =2) shoulders (n = 71) was 4.6 mm (SD 5.5). Previously reported pathologic
      criterion (<6 mm) indicating rotator cuff involvement was fulfilled in 30 (20%)
      of 148 shoulders: in 8 (22%) of 36 shoulders in men and in 22 (20%) of 112
      shoulders in women. All the shoulders with severe rheumatoid destruction (Larsen
      grade 4 or 5) fulfilled the pathologic limit. The subacromial space had a
      significant negative correlation with the GH joint destruction (Larsen grade) in
      both sides: right r = -.63 (95% CI -.75 to -.47), left r = -.71 (95% CI -.81 to 
      .58). Progressive upward migration is an inevitable consequence of rheumatoid
      destruction in the GH joint. A significant step in this process occurred between
      the Larsen grades of 3 and 4, where the mean distance turned negative, indicating
      rotator cuff disease. A patient with rheumatoid arthritis and painful shoulder
      and upward migration of the humerus on the shoulder radiograph should be
      evaluated by an orthopaedic surgeon. In indistinct cases with subacromial space
      diminution, imaging techniques like ultrasonography or magnetic resonance imaging
      may be required to determine the exact pathologic condition of the rotator cuff
      and to select optimal treatment.

PMID- 10888162
TI  - Prediction of muscle force involved in shoulder internal rotation.
AB  - The estimation of shoulder muscle force is important to understand the mechanism
      of rotator cuff injury. In general, mean parameter values are used as input for
      computational models. However, anatomic and biomechanical parameters vary widely
      among people. The purpose of this study was to evaluate shoulder muscle forces
      predicted by an electromyography-driven muscle model given neuromuscular
      parameters generated by Monte Carlo simulation. Normal distributions were used to
      model muscle moment arms; electromyographic and muscle physiological cross
      sectional area data were modeled with log-normal distributions. Eight muscles
      were included in the model. Muscle force and joint moment were predicted on the
      basis of the simulated parameters. The results showed that the subscapularis and
      pectoralis major were substantial actuators for shoulder internal rotation.
      During maximum voluntary contraction the median of the muscle forces of the
      subscapularis and the pectoralis major were 1030 N and 462 N, respectively. This
      study demonstrated that the Monte Carlo method could be used for muscle force
      prediction by integrating population variability of physiological parameter into
      a biomechanical muscle model.

PMID- 10888163
TI  - Quantitative determination of articular pressure in the human shoulder joint.
AB  - The objective of this study was to determine experimentally the effect of
      individual variations in articular surface geometry on the shoulder joint
      pressure distribution in functionally important arm positions. The location and
      size of the load-bearing areas and maximal pressures of 10 cadaver shoulder
      joints were examined at 30 degrees, 90 degrees, and 150 degrees of abduction (+/
      90 degrees external rotation) and 120 degrees flexion with pressure-sensitive
      film. Only parts of the glenoid cavity were involved in the load transfer, some
      specimens showing central and other bicentric (superior-inferior) pressure maxima
      during abduction and flexion. The load-bearing areas were more central at
      external rotation, suggesting that the humeral head is not a perfect sphere. The
      maximal pressure was recorded at 90 degrees of abduction with 90 degrees external
      rotation, with 5.1 MPa for the elevation for single- and >10 MPa for double-arm
      weight. The study demonstrates that shoulder joint pressure cannot be calculated
      analytically but depends on subtle variations of joint incongruity.

PMID- 10888164
TI  - Fixation of proximal humeral prostheses and rotational micromotion.
AB  - Twenty pairs of cadaveric humeri were used to compare the rotational stability of
      proximal humeral prostheses fixed by proximal cementation with the stability
      offered by press fit or full cementation. For each proximally cemented specimen,
      only the upper portion of the prosthesis was coated with cement. For the fully
      cemented specimens, a cement restrictor was used just distal to the prosthesis,
      and a finger-packing technique was used to fill the proximal humeral medullary
      canal. Torque was applied to the Morse taper of the prostheses, and rotational
      micromotion was measured at the level of the osteotomy. In each of 11 pairs of
      cadaveric humeri, one side was press fit and the contralateral side was
      proximally cemented; in each of 9 pairs, proximal cementation was compared with
      full cementation. Proximally cemented prostheses' micromotion was significantly
      less than that of press-fit prostheses (P = .0016). There was no difference in
      micromotion between proximal cementation and full cementation (P = .82). Proximal
      cementation increased initial fixation over press fit. Full cementation did not
      increase rotational stability.

PMID- 10888165
TI  - Function of the rabbit supraspinatus muscle after large detachment of its tendon:
      6-week, 3-month, and 6-month observation.
AB  - Thirty rabbits were anesthetized, and the supraspinatus tendon was detached from
      the greater tuberosity and the infraspinatus and subscapularis tendons. After 6
      weeks (group A), 3 months (group B), and 6 months (group C), in vivo evaluation
      of twitch tension and fatigue index was done. Next, scapulas with muscles were
      examined with computed tomography. The most prominent decrease of twitch tension
      and fatigue index was noted during the first 6 weeks. The twitch tension and
      fatigue index after 2 and 4 minutes of the muscle operated on expressed as a
      percentage of the values developed by healthy contralateral nonoperated muscle
      were 58.2%, 34.5%, and 32.7% at the beginning of stimulation, 45.4%, 35.3%, and
      26.7% after 2 minutes, and 42.5%, 32.6%, and 18.5% after 4 minutes of
      stimulation, respectively, in groups A, B, and C. Computed tomography examination
      showed fatty degeneration of the supraspinatus averaging 1.85 (group A), 2.28
      (group B), and 2.43 (group C). Moderate infraspinatus fatty degeneration was
      noted in all groups. There was no significant fatty degeneration of subscapularis
      muscle.

PMID- 10888166
TI  - The developmental anatomy of the neonatal glenohumeral joint.
AB  - The embryologic development of the capsular ligaments, synovial lining, rotator
      cuff, and bony structures of the shoulder is incompletely understood. The purpose
      of this study is to report the gross and microscopic anatomy of the developing
      glenohumeral joint on the basis of dissections of fetal shoulder specimens. After
      Institutional Review Board approval from our hospital, 51 shoulders in 37 fetal
      specimens were obtained from cases of fetal demise. The gestation time of these
      specimens ranged from 9 to 40 weeks. The morphology of the capsule, labrum, and
      associated ligaments were studied by dissection under a dissecting microscope.
      High-resolution radiographs were made, and sections were processed for routine
      histology. There was noted to be minimal variation in the shape and slope of the
      acromion. The coracoid was much larger in relation to the shoulder than in the
      mature shoulder. The coracoacromial ligament was grossly evident at this stage of
      development, with distinct anterolateral and posteromedial bands in this
      ligament. The inferior glenohumeral ligament was seen as a prominent thickening
      in the capsule, whereas the middle and superior glenohumeral ligaments were
      thinner and more difficult to identify as distinct structures. Upon histologic
      examination, the inferior glenohumeral ligament was seen to consist of several
      layers of organized collagen fibers. The inferior glenohumeral ligament inserted
      into the labrum and margin of the glenoid. The capsule was much thinner in the
      region superior to the inferior glenohumeral ligament. A rotator interval
      capsular defect was often present, and the coracohumeral ligament was seen as a
      distinct structure as early as 15 weeks. A bare spot in the glenoid was not
      observed. This study indicates that some of the important functional elements of
      the structure of the mature human shoulder are present early in development,
      including the glenohumeral and coracohumeral ligaments. The coracoacromial
      ligament plays a significant role in the formation of the coracoacromial arch in
      the neonatal shoulder. The presence of a capsular rotator interval indicates that
      this aspect of capsular anatomy is congenital.

PMID- 10888167
TI  - Repair of distal biceps brachii tendon ruptures.
AB  - This study consisted of 26 male patients with distal biceps tendon ruptures, 2 of
      whom had bilateral injuries, making the total number of ruptures 28. The average
      age at injury was 45 years. The treatment groups were the following: 3 were
      treated without surgery, 4 were repaired with brachialis tenodesis, and 21 were
      reattached to the radial tuberosity by the 2-incision Boyd-Anderson approach.
      Patients underwent follow-up a minimum of 14 months after surgery, with the
      average being 43 months. Outcome was evaluated based on the physical examination,
      isokinetic testing of strength and endurance of flexion and supination, and
      radiographic analysis.

PMID- 10888168
TI  - A simplified method for repair of distal biceps tendon ruptures.
AB  - Repair of distal biceps brachii tendon ruptures is recommended for active
      individuals desiring maximum return of elbow supination and flexion strength. A 2
      incision method of repair has been most popular but carries a risk of radioulnar
      synostosis. In the past, repair through a single anterior incision required more
      dissection and risked injury to the posterior interosseous nerve. The authors
      present a simplified method for the repair of distal biceps tendon ruptures
      through a single anterior incision. The use of suture anchors provides secure
      fixation to the radius with minimal volar dissection. This method was used
      successfully in 16 patients, 8 acutely (<6 weeks) and 8 chronically, with
      excellent functional results. Patients who received acute repairs regained elbow
      strength and power; patients who received chronic repairs showed slight deficits
      of supination strength (16%) and flexion power (14%). Of 10 chronic ruptures
      treated, only 2 tendons could not be mobilized back to the radial tuberosity and
      had to be transferred to the brachialis. There were no failures and no
      complications of radioulnar synostosis or posterior interosseous nerve palsy. The
      single anterior incision approach in which suture anchors are used is recommended
      as an alternative to the traditional 2-incision method.

PMID- 10888169
TI  - Radial tuberosity exostosis as a cause of reduced forearm rotation.

PMID- 10888170
TI  - Suprascapular nerve injury at the spinoglenoid notch after glenoid neck fracture.

PMID- 10888171
TI  - Posterior dislocation of the shoulder with a large fracture segment: a case
      report.

PMID- 10888172
TI  - Hypoplasia of bilateral humeral trochlea associated with unilateral ulnar nerve
      palsy: a case report.

PMID- 10888173
TI  - The treatment of nonunion of the distal humerus by means of a transcondylar rod:
      a report of 3 cases.

PMID- 10888174
TI  - The management of significant glenoid deficiency in total shoulder arthroplasty.

PMID- 10888175
TI  - "Glenohumeral osteoarthrosis after Putti-Platt repair".

PMID- 10888176
TI  - 13 cases of aberrant muscle covering the subscapularis.

PMID- 10888177
TI  - Mandated outpatient treatment: a quick fix for random violence?--Not likely.

PMID- 10888178
TI  - Resource document on mandatory outpatient treatment.
AB  - Mandatory outpatient treatment, or outpatient commitment, refers to court-ordered
      treatment for patients who suffer from severe mental illness and who are unlikely
      to be compliant with such treatment without a court order. Many states already
      have commitment statutes that permit mandatory outpatient treatment, and others
      are considering enacting new legislation or amending existing statutes. This
      Resource Document was prepared under the auspices of the American Psychiatric
      Association's Council on Psychiatry and Law to provide information to those who
      are drafting mandatory outpatient treatment legislation. It begins with a review
      of the history of mandatory outpatient treatment and recent empirical findings,
      followed by a detailed discussion of the salient issues in mandatory outpatient
      treatment. The document concludes with a statement of recommendations concerning
      key provisions in statutory schemes of mandatory outpatient treatment programs.
      This Resource Document endorses the view that mandatory outpatient treatment can
      be a useful intervention for a small subset of noncompliant patients with severe
      and chronic mental illness who go in and out of psychiatric hospitals through the
      so-called "revolving door."

PMID- 10888179
TI  - Commentary: capacity-based involuntary outpatient treatment.

PMID- 10888180
TI  - Commentary: a major advance in the laws pertaining to community treatment for
      persons with severe mental illness.

PMID- 10888181
TI  - Commentary: the law of unintended consequences.

PMID- 10888182
TI  - Commentary: a "systems"-based alternative to mandatory outpatient treatment.

PMID- 10888183
TI  - The case against outpatient commitment.
AB  - Among individuals with severe mental illness, a small proportion commit violent
      acts. Since these individuals are often not engaged in ambulatory treatment,
      there has been a move in the states to legislate and implement outpatient
      commitment programs. The American Psychiatric Association Council on Psychiatry
      and Law has issued a Resource Document that supports the use of mandatory
      outpatient treatment. The purpose of this article is to challenge the logic and
      legitimacy of using the courts to force treatment compliance of individuals who
      are neither incompetent by legal standards nor at imminent risk of harming
      themselves or others.

PMID- 10888184
TI  - Terrorist on trial: the context of political crime.
AB  - When political terrorists stand trial for their violent acts, the political
      context inevitably plays a major role. This article describes the trial of an Abu
      Nidal terrorist tried in federal court for skyjacking an Egyptian airliner. The
      defense portrayed the traumas of the Palestinian people and of the defendant at
      the hands of the Israelis, offering a not guilty by reason of insanity defense on
      the basis of posttraumatic stress disorder. Making sense to the jury of how a
      sane individual could carry out a violent act in which more than 50 innocent men,
      women, and children died was the task of the author, who served as expert for the
      U.S. Department of Justice. The paper describes how the subject was socialized to
      violence in the refugee camps, where he was inspired to be a soldier in the
      revolution in order to reclaim his family lands. Nationalist-separatist terrorism
      is particularly intractable because of the generational transmission of hatred
      and revenge.

PMID- 10888185
TI  - Spousal homicide and suicide in Quebec.
AB  - Domestic violence is a cause for major concern in psychiatry today, yet little is
      known about the amplitude and dynamics of spousal homicide and extended suicide.
      Within the jurisdiction of the Quebec Coroner's Office, the investigation files
      on all consecutive cases of deceased victims of intrafamilial violence occurring
      between 1991 and 1998 were reviewed. Using a validated checklist, a variety of
      variables were systematically collected and reviewed for descriptive analysis.
      Three hundred eighty-eight cases of death were studied. Of this sample, 145 cases
      (37.4%) concerned victims of conjugal homicide. Fifty-eight cases (40.01%)
      concerned victims whose homicidal spouses subsequently killed themselves.
      Suicidal offenders were more likely to be men, to be estranged from their spouse
      through separation, and, most often, to have used a firearm in the commission of
      the extended homicide-suicide. The majority of offenders suffered from clinical
      symptoms of depression. This study emphasizes the need to develop a detailed tool
      to assist coroners in the field and police investigators with the gathering of
      specific information that will be of use to clinical researchers.

PMID- 10888186
TI  - Predictions of violent and total infractions among institutionalized male
      juvenile offenders.
AB  - Forensic practitioners in settings with institutionalized adolescent offenders
      are frequently responsible for the accurate classification of problematic and
      potentially violent youths. Methods of assessment often include traditional
      tests, such as the MMPI and MMPI-A, and interview-based determinations of
      psychopathy. In a study of residential male adolescent offenders, the MMPI-A and
      the Screening Version of the Psychopathy Checklist (PCL:SV) were used to predict
      total, violent, self-injurious, and nonviolent infractions in a treatment
      oriented facility for delinquents. In predicting the overall number of
      infractions, the MMPI-A was superior to the PCL:SV. Psychopaths manifested a
      significantly higher rate of violent infractions than nonpsychopaths. Finally,
      ethnic differences raise serious concerns about the generalizability of the
      PCL:SV; differences were found in the relationship between psychopathy and
      infractions based on ethnicity.

PMID- 10888187
TI  - Same-gender stalking.
AB  - Although stalkers most commonly target victims of the opposite gender, the
      results of larger and less selective studies suggest that same-gender stalking
      occurs with greater frequency than formerly thought. This study reviews the
      exiguous literature on same-gender stalking and presents the findings from a
      clinical study of 29 same-gender stalking cases that were referred to a forensic
      psychiatry center. The demographic characteristics, behavior, motivations, and
      psychopathology of same-gender stalkers are compared with a sample of 134
      opposite-gender stalkers. The two groups were similar in many respects, with some
      discrepancies evident in the prior relationship between victim and stalker,
      harassment methods, and stalking motives. The impact of same-gender stalking on
      its victims is examined, and the implications of these findings are discussed.

PMID- 10888188
TI  - Promoting research in forensic psychiatry.

PMID- 10888189
TI  - Transitioning individuals with mental retardation and developmental disability:
      The other sister.

PMID- 10888190
TI  - Canadian landmark case, Winko v. British Columbia: revisiting the conundrum of
      the mentally disordered accused.

PMID- 10888191
TI  - The Foreign Intelligence Surveillance Act: law enforcement's secret weapon.

PMID- 10888192
TI  - Insanity acquittees and rearrest: the past 24 years.

PMID- 10888193
TI  - Behind bars: personality disorders.
AB  - Individuals with severe, function-impairing personality disorders comprise a
      large proportion of the difficult-to-manage inmates. Personality disorders are
      reliably diagnosable using standardized criteria (DSM-IV), and treatment options
      are now available. Through careful assessment, differential diagnosis, and
      differential therapeutic selection, clinicians have the opportunity to help these
      individuals gain more control over unstable affect, impulsive/ irritable
      aggression, and paranoid perceptual distortions. Appropriate intervention holds
      the possibility, if not the promise, of reduced morbidity and recidivism, and may
      reasonably contribute to the public safety mission of corrections and to the
      primary mission of clinicians, which is improved health.

PMID- 10888194
TI  - Attorney's pressures on the expert witness.

PMID- 10888195
TI  - Assaultive eye injury and enucleation.

PMID- 10888196
TI  - Assaultive eye injury and enucleation.

PMID- 10888197
TI  - Studies on the conformational properties of CP-10(42-55), the hinge region of CP
      10, using circular dichroism and RP-HPLC.
AB  - The conformational properties of CP-10(42-55), a peptide corresponding to the
      hinge region of CP-10, were investigated using circular dichroism spectroscopy
      and reverse-phase high-performance liquid chromatography (RP-HPLC). The circular
      dichroism studies indicated that CP-10(42-55) formed considerable secondary
      structure in the presence of hydrophobic solution environments including 50%
      acetonitrile, 50% trifluoroethanol and 200 mM sodium dodecyl sulfate, which
      comprised a mixture of alpha-helix and beta-sheet. The effect of temperature on
      the conformation of CP-10(42-55) was investigated between 5 and 40 degrees C,
      with very small changes in the spectra being observed. RP-HPLC was then used to
      investigate the effect of temperature on the conformation of CP-10(42-55) in the
      presence of a hydrophobic surface. Using a C18-adsorbent, CP-10(42-55) exhibited
      a conformational transition at 25 degrees C, which was associated with an
      increase in the chromatographic contact area and the binding affinity of the
      peptide for the stationary phase. In addition, near-planar bandbroadening
      behaviour indicated that conformational species interconverted with rapid rate
      constants compared with the chromatographic time scale. These results indicated
      that the conformational change at 25 degrees C in the RP-HPLC system most likely
      corresponds to the unfolding of an alpha-helical and/or beta-sheet structure to
      an extended coil structure. Therefore, the strong chemotactic properties of this
      peptide may be attributed to its ability to form considerable secondary structure
      in the presence of a hydrophobic environment.

PMID- 10888198
TI  - Effect of maurotoxin, a four disulfide-bridged toxin from the chactoid scorpion
      Scorpio maurus, on Shaker K+ channels.
AB  - Maurotoxin is a 34-residue toxin isolated from the venom of the Tunisian chactoid
      scorpion Scorpio maurus palmatus and contains four disulfide bridges that are
      normally found in long-chain toxins of 60-70 amino acid residues, which affect
      voltage-gated sodium channels. However, despite the unconventional disulfide
      bridge pattern of maurotoxin, the conformation of this toxin remains similar to
      that of other toxins acting on potassium channels. Here, we analyzed the effects
      of synthetic maurotoxin on voltage-gated Shaker potassium channels (ShB)
      expressed in Xenopus oocytes. Maurotoxin produces a strong, but reversible,
      inhibition of the ShB K+ current with an IC50 of 2 nM. Increasing concentrations
      of the toxin induce a progressively higher block at saturating concentrations. At
      nonsaturating concentrations of the toxin (5-20 nM), the channel block appears
      slightly more pronounced at threshold potentials suggesting that the toxin may
      have a higher affinity for the closed state of the channel. At the single channel
      level, the toxin does not modify the unitary current amplitude, but decreases
      ensemble currents by increasing the number of depolarizing epochs that failed to
      elicit any opening. A point mutation of Lys23 to alanine in maurotoxin produces a
      1000-fold reduction in the IC50 of block by the toxin suggesting the importance
      of this charged residue for the interaction with the channel. Maurotoxin does not
      affect K+ currents carried by Kir2.3 channels in oocytes or Na+ currents carried
      by the alphaIIa channel expressed in CHO cells.

PMID- 10888199
TI  - Synthesis of different types of dipeptide building units containing N- or C
      terminal arginine for the assembly of backbone cyclic peptides.
AB  - Different types of dipeptide building units containing N- or C-terminal arginine
      were prepared for synthesis of the backbone cyclic analogues of the peptide
      hormone bradykinin (BK: Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg). For cyclization in
      the N-terminal sequence N-carboxyalkyl and N-aminoalkyl functionalized dipeptide
      building units were synthesized. In order to avoid lactam formation during the
      condensation of the N-terminal arginine to the N-alkylated amino acids at
      position 2, the guanidino function has to be deprotected. The best results were
      obtained by coupling Z-Arg(Z)2-OH with TFFH/collidine in DCM. Another dipeptide
      building unit with an acylated reduced peptide bond containing C-terminal
      arginine was prepared to synthesize BK-analogues with backbone cyclization in the
      C-terminus. To achieve complete condensation to the resin and to avoid side
      reactions during activation of the arginine residue, this dipeptide unit was
      formed on a hydroxycrotonic acid linker. HYCRAM technology was applied using the
      Boc-Arg(Alloc)2-OH derivative and the Fmoc group to protect the aminoalkyl
      function. The reduced peptide bond was prepared by reductive alkylation of the
      arginine derivative with the Boc-protected amino aldehyde, derived from Boc-Phe
      OH. The best results for condensation of the branching chain to the reduced
      peptide bond were obtained using mixed anhydrides. Both types of dipeptide
      building units can be used in solid-phase synthesis in the same manner as amino
      acid derivatives.

PMID- 10888200
TI  - Stereoselective deuterium labeling of proR beta-protons in the NMR structure
      determination of a helix-turn-helix turn peptide mimic.
AB  - The NMR structure of a small, side-chain-cyclized tripeptide mimic of the turn in
      the helix-turn-helix (HTH) motif was determined. The four beta-protons were
      stereospecifically assigned by stereoselective deuterium replacement of only the
      proR beta-protons. All 24 of 30 NOESY cross-peaks not involving chemically
      defined or freely rotating protons, and six of seven coupling constants from the
      P.COSY were used as distance and angle constraints in molecular modeling.
      MacroModel found 33/1000 structures in the NMR constrained search and 263/1000
      structures in the unconstrained search, indicating meaningful constraint by the
      NMR data. However, the 10 lowest-energy structures from the unconstrained and
      constrained searches are very similar, so modeling alone was able to find the
      experimentally determined structure.

PMID- 10888201
TI  - Synthesis and anti-aggregatory activity of linear retro-inverso RGD peptides.
AB  - Six retro-inverso tri- and tetrapeptide analogues of RGD were prepared and their
      anti-aggregatory activity was determined by platelet aggregation tests in
      comparison with the corresponding parent peptides. An efficient method for the
      introduction of a malonyl-aspartic residue into a peptide chain is described for
      the first time. A 2-3-fold decrease in potency or total loss of bioactivity was
      observed with the new peptides; structure-activity relationships are discussed.

PMID- 10888202
TI  - Structures of the intradiskal loops and amino terminus of the G-protein receptor,
      rhodopsin.
AB  - The intradiskal surface of the transmembrane protein, rhodopsin, consists of the
      amino terminal domain and three loops connecting six of the seven transmembrane
      helices. This surface corresponds to the extracellular surface of other G-protein
      receptors. Peptides that represent each of the extramembraneous domains on this
      surface (three loops and the amino terminus) were synthesized. These peptides
      also included residues which, based on a hydrophobic plot, could be expected to
      be part of the transmembrane helix. The structure of each of these peptides in
      solution was then determined using two-dimensional 1H nuclear magnetic resonance.
      All peptide domains showed ordered structures in solution. The structures of each
      of the peptides from intradiskal loops of rhodopsin exhibited a turn in the
      central region of the peptide. The ends of the peptides show an unwinding of the
      transmembrane helices to form this turn. The amino terminal domain peptide
      exhibited alpha-helical regions with breaks and bends at proline residues. This
      region forms a compact domain. Together, the structures for the loop and amino
      terminus domains indicate that the intradiskal surface of rhodopsin is ordered.
      These data further suggest a structural motif for short loops in transmembrane
      proteins. The ordered structures of these loops, in the absence of the
      transmembrane helices, indicate that the primary sequences of these loops are
      sufficient to code for the turn.

PMID- 10888203
TI  - Single nucleotide polymorphism to disclose severe side-effects or proper dosage
      for each patient.

PMID- 10888204
TI  - How do we treat patients with hepatitis C virus associated-glomerulonephritis?

PMID- 10888205
TI  - Vascular endothelial growth factor and platelets.

PMID- 10888206
TI  - Antiphospholipid syndrome in the elderly.

PMID- 10888207
TI  - Left ventricular aneurysm without coronary artery disease, incidence and clinical
      features: clinical analysis of 11 cases.
AB  - OBJECTIVE: To examine the incidence, underlying disease and clinical features of
      left ventricular aneurysm (LVA) not related to coronary artery occlusion.
      METHODS: Retrospective review of consecutive patients who underwent both left
      ventriculography and coronary angiography. PATIENTS: LVA was confirmed in 11 of
      2,348 consecutive patients (0.47%). RESULTS: The location of LVA was mainly in
      the apical region (81.8%). In five of the 11 patients (45.5%), the underlying
      heart disease was hypertrophic cardiomyopathy (HCM), including 4 patients of
      dilated phase and one patient of midventricular type. The serial ECG changes from
      left ventricular hypertrophy to abnormal Q wave and endomyocardial biopsy were
      useful for the differential diagnosis of these cases against myocardial
      infarction. The underlying disease of the remaining patients was: myocarditis (2
      patients), arrhythmogenic right ventricular dysplasia (1 patient), Chagas'
      disease (1 patient), glycogen storage disease (1 patient), and sarcoidosis (1
      patient). Ventricular tachycardia appeared in 9 of 11 cases (81.8%) including 2
      patients with sustained ventricular tachycardia. CONCLUSION: LVA formation
      without coronary artery disease was a rare phenomenon. The underlying disease was
      varied but the incidence of hypertrophic cardiomyopathy in the dilated phase was
      comparatively high. Ventricular tachycardia was a significant complication in
      these patients.

PMID- 10888208
TI  - Allele frequency of human endothelial nitric oxide synthase gene polymorphism in
      abdominal aortic aneurysm.
AB  - OBJECTIVE: This study was performed to examine the role of the endothelial
      constitutive NO synthase (ecNOS) gene in patients with abdominal aortic aneurysm
      (AAA). METHODS: We determined the distributions of polymorphism in intron 4 of
      the ecNOS (ecNOS4) gene, amplified by polymerase chain reaction, and compared the
      allele frequencies between subjects with abdominal aortic aneurysms (AAAs) and
      healthy individuals. PATIENTS: Fifty-eight patients with AAAs and 410 race
      matched healthy controls were studied. RESULTS: Two alleles of the ecNOS4 gene,
      containing 4 (a-allele) and 5 (b-allele) repeats, were identified. We found that
      the a-allele frequency of this gene was significantly higher in the surgical than
      in the non-surgical group. CONCLUSION: The results of this study suggest that the
      a-allele of the ecNOS4 gene is indicative of the need for surgery for AAA.
      Analysis of the alleles of the ecNOS4 gene polymorphism could provide useful
      information concerning the clinical course of AAA progression.

PMID- 10888209
TI  - Predictive value of remnant-like particle cholesterol as an indicator of coronary
      artery stenosis in patients with normal serum triglyceride levels.
AB  - OBJECTIVE: We designed the present study to evaluate the association of various
      lipid and fibrinolytic components with coronary artery stenosis with respect to
      the triglyceride (TG) level. METHODS: Levels of TG, remnant-like particle
      cholesterol (RLP-C), total cholesterol, high-density lipoprotein cholesterol (HDL
      C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-(a), uric acid,
      blood glucose, tissue plasminogen activator (t-PA), t-PA inhibitor type 1,
      antithrombin III, and protein C were measured in 208 patients who underwent
      diagnostic coronary angiograms. PATIENTS: Of these 208 patients, 59 were
      hypertriglyceridemic (150 mg/dl or higher) and 149 were normotriglyceridemic.
      RESULTS: Both LDL-C and HDL-C showed significant differences between patients
      with and those without coronary artery stenosis in both hypertriglyceridemic and
      normotriglyceridemic patient subgroups. However, RLP-C showed a significant
      difference in the normotriglyceridemic patient subgroup (p=0.012) but not in the
      hypertriglyceridemic patient subgroup (p=0.736). CONCLUSION: Our current
      retrospective study disclosed that RLP-C levels are closely associated with
      coronary artery stenosis in patients with normal TG levels.

PMID- 10888210
TI  - Eotaxin levels in pleural effusions: comparison with monocyte chemoattractant
      protein-1 and IL-8.
AB  - OBJECTIVE: In order to investigate the role of eotaxin in pleural diseases, we
      measured eotaxin in pleural effusions and studied the relationship between
      eotaxin levels and recruitment of inflammatory cells, particularly eosinophils.
      Interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) levels were
      also measured for comparison. METHODS: We evaluated 47 pleural effusion samples,
      7 transudates and 40 exudates. The exudates consisted of 19 malignant, 11
      tuberculous, and 5 parapneumonic effusions, and 5 effusions of other etiologies.
      Chemokine levels were measured by specific sandwich enzyme-linked immunosorbent
      assays. RESULTS: Eotaxin was detected in all samples examined, but the levels did
      not differ significantly among the exudates. There was no significant correlation
      between the levels of eotaxin and MCP-1 or IL-8. The level of eotaxin but not the
      others was significantly higher in eosinophilic effusions (>10% eosinophils among
      white blood cells in the fluid) than in non-eosinophilic fluids. The number of
      eosinophils in pleural effusions was significantly correlated with the eotaxin
      levels, but not with the levels of other chemokines. The number of neutrophils
      was significantly correlated with IL-8 but not with the others. CONCLUSIONS:
      Results suggest that eotaxin contributes to the migration of eosinophils in
      pleural inflammation. Taken together with the correlation between IL-8 and
      neutrophils, it appears that the predominant type of pleural inflammatory
      infiltrate is controlled, at least in part, by the subgroup of chemokines
      expressed in the pleural space.

PMID- 10888211
TI  - Type II citrullinemia in an elderly patient treated with living related partial
      liver transplantation.
AB  - A 60-year-old woman was admitted to our hospital for repeated consciousness
      disturbance. Blood examination showed hyperammonemia, and plasma amino acid
      analysis revealed a marked increase in the citrulline level. To establish a
      diagnosis, a percutaneous needle biopsy of the liver was performed. The
      determination of the urea cycle enzyme activities revealed a selective marked
      decrease in argininosuccinate synthetase activity, indicating the final diagnosis
      of type II citrullinemia. The mean survival period of this disease after the
      appearance of symptoms has been reported as 26.4 months, and most conservative
      treatments are not effective. We performed a living related partial liver
      transplantation. Over the subsequent 13-month follow-up, the patient's condition
      has remained fairly good.

PMID- 10888212
TI  - Cowden's disease diagnosed through mucocutaneous lesions and gastrointestinal
      polyposis with recurrent hematochezia, unrevealed by initial diagnosis.
AB  - A 51-year-old man was admitted to our hospital because of hematochezia and
      painful keratotic plaques involving both hands. He had gastrointestinal
      polyposis, and a history of liver hemangiomas and thyroid tumor. Numerous papules
      on the face and papillomatosis on the oral mucosa were present. A diagnosis was
      made as a typical case of Cowden's disease according to the criteria proposed by
      Salem and Steck (J Am Acad Dermatol 8: 686, 1983). The patient was not correctly
      diagnosed initially in spite of typical manifestations of Cowden's disease,
      mainly due to his concomitant manifestations which occurred chronologically.

PMID- 10888213
TI  - Cryofiltration and oral corticosteroids provide successful treatment for an
      elderly patient with cryoglobulinemic glomerulonephritis associated with
      hepatitis C virus infection.
AB  - A 75-year-old man was admitted due to nephrotic syndrome, purpura on the legs,
      which was associated with hepatitis C virus (HCV), and type II mixed
      cryoglobulinemia. Renal biopsy revealed features of cryoglobulinemic
      glomerulonephritis. Since the patient was elderly and the HCV genotype was Ib,
      interferon-alpha for reducing HCV was not indicated. Four sessions of
      cryofiltration and the administration of corticosteroids improved the proteinuria
      and renal function strikingly without adverse effects. This case demonstrates
      that an elderly patient who has nephrotic syndrome caused by cryoglobulinemic
      glomerulonephritis associated with HCV can be treated safely by cryofiltration
      with low doses of oral corticosteroids.

PMID- 10888214
TI  - High fever, renal failure, disseminated intravascular coagulation and
      myelodysplasia accompanied with enhanced angiogenesis possibly due to
      overexpression of vascular endothelial growth factor.
AB  - A 44-year-old woman suffered from recurrent fever, edema and fatigue. Laboratory
      data revealed renal dysfunction, low proteinemia, disseminated intravascular
      coagulation (DIC) and myelodysplasia. A renal and lymph node biopsy showed a
      marked angiogenesis. Serum levels of vascular endothelial growth factor (VEGF),
      and interleukin (IL)-6 were markedly increased, suggesting a pathogenesis related
      to VEGF-induced angiogenesis. The symptoms were remitted after treatment with
      cyclosporin A. No evidence of solid tumors, malignant lymphoma, Castleman's
      disease or POEMS (polyneuropathy, organomegaly, endocrine disorder, M-proteinemia
      and skin change) syndrome, reported to induce a high serum VEGF level, was
      obtained. This case may have involved an unknown mechanism which induced an
      overexpression of VEGF and IL-6.

PMID- 10888215
TI  - Extensively calcified hemangioma of the diaphragm with increased 99mTc
      hydroxymethylene diphosphonate uptake.
AB  - A 31-year-old woman visited an out-patient clinic, because of low-grade fever and
      general fatigue. She was referred to our hospital and admitted for examination of
      an abnormal shadow which had been found on the chest radiograph. She had
      experienced faint right lateral chest pain several times on the deep
      inspirations. Chest radiography showed a mass shadow with calcification in the
      right lower lung field on the mediastinal side. Chest radiographic computed
      tomography showed a 6x6 cm tumor in the right lung field. There were low-density
      areas with septae inside the tumor. Bone scintigraphy showed extremely high
      uptake of (99m)Tc-HMDP in the tumor. After surgical resection and pathological
      examination, we concluded that the tumor was an extensively calcified benign
      hemangioma of the diaphragm.

PMID- 10888216
TI  - Paragonimiasis miyazakii associated with bilateral pseudochylothorax.
AB  - A 37-year-old man who suffered from bilateral pleural effusions, subcutaneous
      abdominal induration and blood eosinophilia, was admitted to our hospital. He had
      ingested raw crabs at a pub-restaurant before the onset of his symptoms. His
      pleural effusions were chyliform containing cholesterol crystals, and a high
      level of immunoglobulin E (36,580 IU/ml) and anti-Paragonimus miyazakii antibody
      were detected. He was effectively treated with praziquantel. This case suggests
      that paragonimiasis should be strongly suspected if blood eosinophilia,
      pseudochylothorax, and a high level of immunoglobulin E in pleural effusion are
      detected.

PMID- 10888217
TI  - Superficial temporal artery dilatation in a patient with infectious temporal
      headache clinically mimicking temporal arteritis.
AB  - A 57-year-old woman noticed a pulsatile shooting headache in her right temporal
      region 3 days after extraction of a tooth from the right mandible. The following
      day, a localized headache over the right superficial temporal artery (STA), low
      grade fever, and jaw claudication appeared and progressed subacutely. Seven days
      after the onset, magnetic resonance imaging and angiography (MRI/MRA) disclosed
      inflammatory swelling of the right temporal muscle and dilatation of the right
      STA. All the symptoms disappeared following antibiotic treatment, and
      neuroimaging findings were improved. In conclusion, MRA is thought to be useful
      to non-invasively identify reversible inflammatory dilatation of extracranial
      vessels.

PMID- 10888218
TI  - Antiphospholipid syndrome with cortical blindness resulting from infarction
      around the posterior cerebral artery in an elderly woman.
AB  - An 87-year-old woman with antiphospholipid syndrome accompanied by cortical
      blindness and thalamic syndrome resulting from infarction of the posterior
      cerebral artery is reported. She was hospitalized because of laceration of the
      head. Two months later, she complained of loss of visual acuity, sharp pain and
      numbness involving the left half of the body except her face. New right posterior
      lobe infarction and the existence of old left infarctions were confirmed by
      serial CT scans. Helical CT scan revealed embolization of the posterior cerebral
      artery with atherosclerotic stenosis. Serological examination showed biologically
      false-positive and positive findings for lupus anticoagulant. She was treated
      with warfarin potassium and clonazepam.

PMID- 10888219
TI  - Influenza in three patients with human immunodeficiency virus infection.
AB  - Three Japanese outpatients with human immunodeficiency virus (HIV) infection on
      anti-retroviral therapy showed evidence of influenza in January 1999. CD4+ T cell
      counts of these patients prior to the diagnosis of influenza were 72, 248, and
      152/mm3, and HIV RNA levels were 19,953, 1,259, and 1,585 copies/ml,
      respectively. Fever continued 4 to 5 days with no severe complications. One
      patient showed post-influenzal bronchitis which was effectively treated by
      antibiotics. None of these patients showed increased serum HIV RNA levels during
      and after influenza, however, in one patient, a transient reduction of CD4+ and
      CD8+ cells was seen during the active phase of influenza. Although symptoms of
      influenza in HIV carriers are generally mild and similar to those in healthy
      adults, careful follow-up is needed as symptoms of influenza in some HIV-infected
      patients can be prolonged and serious.

PMID- 10888220
TI  - Regulation of phospholipase D from human hepatocarcinoma cell line by purine
      nucleotides and protein kinase A.
AB  - The regulation of phosphatidylcholine-specific phospholipase D by purine
      nucleotides and protein kinase A were studied in vitro using an enzyme
      preparation partially purified from the membranous fraction of 7721
      hepatocarcinoma cells. It was found that the enzyme activity was elevated by low
      concentrations of some purine nucleotides, but the activating effects were
      decreased when the concentrations of the nucleotides were higher. The optimal
      concentrations of GTP, GTPgamma[S], GDP and ATP for maximal activation were 0.1
      mM, 5 microM, 1 mM and 1 mM respectively. The activation caused by 1 mM ADP was
      lower. The enzyme was not activated by 1 mM AMP, but significant activation was
      observed by the addition of 1 mM cAMP. The latter was mediated by protein kinase
      A, as a specific inhibitor of protein kinase A abolished the activation. There
      were synergic effects between ATP and GTP, ATP and PIP2, but not between ATP and
      GTPgamma[S], or PIP2 and GTPgamma[S]. The activating effects of GTP and ATP were
      abolished by neomycin, a PIP2 scavenger. These results suggest that phospholipase
      D is regulated by GTP-binding protein and the presence of PIP2 is required for
      the activation induced by GTP. Protein kinase A may be another protein kinase in
      addition to protein kinase C and protein tyrosine kinase which regulate the
      activity of phospholipase D, when the intracellular concentration of cAMP is
      increased.

PMID- 10888221
TI  - Effects of atorvastatin treatment on the oxidatively modified low density
      lipoprotein in hyperlipidemic patients.
AB  - Atorvastatin is an established HMG-CoA reductase inhibitor which effectively
      reduces the plasma low density lipoprotein (LDL)-cholesterol level in
      hyperlipidemic patients. The present study was designed to investigate whether
      atorvastatin treatment can modify the biochemical content of oxidized LDL in
      hyperlipidemic patients and the ability of oxidized LDL to impair the endothelium
      dependent relaxation of blood vessels. With atorvastatin (10 mg/day) treatment
      for 4 weeks in 19 type IIa hyperlipidemic patients, total cholesterol level was
      lowered by 23%, LDL-cholesterol was lowered by 32% and triacylglycerol was
      lowered by 19% as compared with dietary therapy alone. High density lipoprotein
      levels increased by approximately 9%. The ability of oxidized LDL from
      hyperlipidemic patients after atorvastatin treatment to impair the endothelium
      dependent relaxation was significantly reduced as compared with dietary
      intervention alone. Analysis of the biochemical contents of oxidized LDL from
      this group revealed that there was an 11% reduction in lysophosphatidylcholine
      (LPC) as compared with the group that received only dietary counseling. A
      decrease in the C16:0 moiety with a corresponding increase in the C18:0 moiety of
      LPC in the oxidized LDL was also observed in the atorvastatin treated group. We
      propose that the observed reduction and the change in composition of acyl groups
      in LPC in the oxidized LDL of the atorvastatin-treated group results from a
      combination of the continued dietary treatment as well as drug therapy. In view
      of an observation that both C16:0 and C18:0 LPC species are equally potent in the
      impairment of endothelium-dependent relaxation of the aortic rings, we feel that
      the reduced level of LPC in the oxidized LDL produced by atorvastatin treatment
      is partially responsible for the improvement in endothelium control of vascular
      tone.

PMID- 10888222
TI  - Glycochenodeoxycholic acid (GCDC) induced hepatocyte apoptosis is associated with
      early modulation of intracellular PKC activity.
AB  - The effect of GCDC-induced apoptosis on PKC activity and PKC's role in GCDC
      induced hepatocyte apoptosis is unclear. The specific aims of this study were to
      determine if GCDC-induced apoptosis changed intracellular PKC activity and if
      modulation of PKC activity affected GCDC-induced hepatocyte apoptosis. Apoptosis
      was induced in isolated hepatocytes using GCDC. PKC activity was measured and
      specific PKC and calpain inhibitors were used to study the effects of PKC and
      calpain modulation on GCDC-induced apoptosis. After 4 h exposure, 50 microM GCDC
      induced apoptosis in 42% of hepatocytes. Intracellular PKC activity decreased to
      44% of controls 2 h after exposure of hepatocytes to GCDC (p < 0.001). Pre
      incubation of hepatocytes with the calpain protease inhibitor restored PKC
      activity in GCDC exposed hepatocytes to 91 +/- 5% of control cells. Pre
      incubation of hepatocytes with a calpain inhibitor decreased GCDC-induced
      apoptosis as did pre-incubation with the PKC activating phorbol ester, PMA. The
      combination of calpain inhibition and PMA further reduced GCDC-induced apoptosis
      but caused low level hepatic apoptosis. Inhibition of PKC with chelerythrine also
      substantially reduced GCDC-induced hepatocyte apoptosis. GCDC-induced apoptosis
      is associated with decreases in total cellular PKC activity, which appear to be
      dependent on intracellular calpain-like protease activity. The combination of
      protease inhibition and phorbol ester pretreatment preserved total cellular PKC
      activity and decreased GCDC-induced apoptosis but induced low level apoptosis in
      the absence of GCDC exposure. PKC inhibition also decreased GCDC-induced
      hepatocyte apoptosis highlighting the complex interactions of PKC and proteases
      during GCDC-induced apoptosis.

PMID- 10888223
TI  - Changes in ganglioside contents, plasma sialic acid and cAMP levels in
      experimental hepatoma in mice.
AB  - The present study was designed to assess whether changes in glycolipids and
      cyclic AMP contents might serve as markers for the diagnosis of malignancy in the
      liver. The experimental model was a transplantable murine hepatoma. Experimental
      mice were divided into three groups: (1) a therapeutic group, which had been
      transplanted with hepatoma and treated with the antimetabolism drug 5
      fluorouracil (0.2 mg/day i.p.), (2) a control group, which had been transplanted
      with hepatoma and treated with 0.2 ml 0.9% NaCl/day and (3) a normal group of
      mice. The ganglioside and cAMP contents in the hepatoma tissue, plasma cAMP,
      total- and lipid-bound sialic acid levels and red blood cell membrane sialic acid
      levels were determined. Results showed that the ganglioside content, total and
      lipid-bound sialic acid levels in the control group were significantly higher
      than those in the livers of normal mice (p < 0.01) while these respective values
      in the therapeutic group were significantly lower than those in the control group
      (p < 0.01). The cAMP levels of tumor tissues and plasma in the control group were
      lower than those in normal mice. No significant difference in red blood cell
      membrane sialic acid content was observed between the therapeutic and control
      groups though levels for both were higher than those in normal mice. These
      results indicate that ganglioside content and sialic acid levels in hepatoma
      tissues were significantly elevated, and cAMP levels in hepatoma tissues were
      significantly decreased during proliferation and abnormal differentiation.

PMID- 10888224
TI  - Effect of magnesium tanshinoate B on the production of nitric oxide in
      endothelial cells.
AB  - Nitric oxide (NO) is a potent vasodilator which plays an important role in
      regulating vascular tones. Danshen, a Chinese herbal medicine has been widely
      used for the treatment of cardiovascular diseases. The objective of this study
      was to investigate the effect of magnesium tanshinoate B (MTB), a compound
      purified from Danshen, on the production of NO in human endothelial cell line
      (ECV304). After cells were incubated with MTB (1-10 microM) for 1 or 4 h, amounts
      of NO metabolites released by cells were quantified and cellular NOS activities
      were determined following the conversion of [3H]arginine to [3H]citrulline. The
      NOS protein expression was determined by Western immunoblotting analysis. MTB (1
      10 microM) stimulated the release of NO and its metabolites from endothelial
      cells. Following MTB treatment, the cellular NOS activities were significantly
      enhanced with a concomitant increase in the levels of constitutive NOS (cNOS)
      protein mass (110-178%). Selective activation of cNOS by MTB may be employed
      therapeutically in modulating NO production in endothelial cells.

PMID- 10888225
TI  - Effect of Flos carthami on stress-activated protein kinase activity in the
      isolated reperfused rat heart.
AB  - The apoptotic death of cardiomyocytes due to ischemia/reperfusion is one of the
      major complications of heart disease. Ischemia/reperfusion has been shown to lead
      to the activation of the stress-activated protein (SAP) kinases and the
      p38/reactivating kinase (p38/RK). In this study, the direct effect of an aqueous
      Flos carthami (FC) extract on SAP kinases was investigated. When isolated rat
      hearts were perfused by Langendorff mode with media containing FC extract prior
      to the induction of global ischemia and the subsequent reperfusion, SAP kinase
      activity was inhibited 95%. Untreated ischemic/reperfused hearts showed a 57%
      elevation in the activity of SAP kinase. The in vitro effect of these FC extracts
      on SAP kinase was also tested. At a concentration of 10 microg/ml, the aqueous FC
      extract resulted in 50% inhibition of SAP kinase activity in ischemic heart
      tissue. Our results showed that FC affected both the interaction of SAP kinase
      with c-jun as well as the phosphotransferase reaction. These results clearly
      demonstrate that extracts from Flos carthami exerted inhibitory effects on SAP
      kinase. The administration of the FC extract may lead to a modulation of the
      apoptotic effect of SAP kinase activation induced during ischemia/reperfusion.

PMID- 10888226
TI  - Over expression of integrin alpha 5 beta 1 in human hepatocellular carcinoma cell
      line suppresses cell proliferation in vitro and tumorigenicity in nude mice.
AB  - Integrin alpha 5 beta 1 and alpha 2 beta 1 are the major integrin receptors in
      human hepatocytes. However, in human hepatocellular carcinoma cells it was found
      that the expression of integrin alpha 5 beta 1 was decreased and another integrin
      alpha 6 beta 1 increased. In this study, the SMMC7721 human hepatocellular
      carcinoma cells cotransfected or singly transfected with integrin alpha 5 and/or
      beta 1 cDNAs were established, and designated alpha 5 beta 1.6-7721, alpha 5.3
      7721, and beta 1.6-7721 cell lines, respectively. Transfection with cDNAs of
      integrin alpha 5 and beta 1 subunits resulted in the over expression of each
      integrin and modified biological properties, including a slowed growth rate,
      changes in the cell cycle from 15.5% of control cells in the G2/M phase to 12.1%,
      9.6% and 9.4% in alpha 5.3-7721, beta 1.6-7721, alpha 5 beta 1.6-7721,
      respectively, and a decrease in the Cell Mitosis Index from 1.6 in controls to
      0.96, 0.95, and 0.72, and 34%, 28% and 52% derived from colony forming ability,
      respectively. Tumorigenicity was also tested in nude mice with inoculation of
      cells subcutaneously. Tumor masses growing in nude mice following inoculation
      with beta 1.6-7721, and alpha 5 beta 1.6-7721 cells weighed only 52% or 31% those
      of control cells. These results indicated that deletion or low expression of
      integrin alpha 5 beta 1 may play an important role in the development of
      hepatocellular carcinoma. Therefore, induction of expression of the integrin
      alpha 5 beta 1 in malignant cells could be a potential means of treating
      hepatocellular carcinoma.

PMID- 10888227
TI  - Apolipoprotein C-III can specifically bind to hepatic plasma membranes.
AB  - Apo C-III plays an important role in the metabolism of plasma triglyceride, which
      can delay the catabolism of triglyceride-rich lipoproteins by interfering with
      apo E-mediated receptor clearance of remnant particles from plasma. The mechanism
      of the interference has not yet been defined. To further explore the role of apo
      C-III, we first injected mice with 125I-apo C-III. The measurement of
      radioactivity showed that liver took up 3.3-10 fold as much radioactivity as
      other organs such as heart, spleen, lung, kidney, stomach, large intestine, small
      intestine, and muscle. This was confirmed by incubating the tissue homogenates of
      the organs with 125I-apo C-III that the radiolabeled apo C-III specifically bound
      to only hepatic homogenate. To investigate which subcellular part or parts of
      hepatic cells play the role of binding to apo C-III, hepatic cell components of
      nucleus, mitochondria, microsomes and plasma membranes were then incubated with
      125I-apo C-III. The radiolabeled apo C-III could specifically bind to only
      hepatic plasma membranes. Finally hepatic plasma membranes were purified to study
      the characteristics of the specific binding with apo C-III. Addition of
      increasing concentration of 125I-apo C-III to human hepatic plasma membranes
      revealed saturable binding to membranes with a Kd of 0.31 +/- 0.07 micromol/l.
      The maximum specific binding capacity was 1.74 +/- 0.45 microg apo C-III/mg
      membrane protein. In competition studies using unlabeled apo C-III and isolated
      lipoproteins HDL, LDL and VLDL, only apo C-III and VLDL effectively competed with
      125I-apo C-III for membrane binding. The binding of 125I-apo C-III to human liver
      plasma membranes was Ca2+-independent, and was abolished when plasma membranes
      were treated with trypsin. The characteristics of 125I-apo C-III binding to mouse
      liver plasma membranes were similar to those of human liver plasma membranes with
      the exception of a binding maximum of 1.52 +/- 0.39 microg apo C-III/mg membrane
      protein. We conclude that apo C-III exhibits high-affinity binding to hepatic
      plasma membranes, which is saturable, reverse and specific.

PMID- 10888228
TI  - Acetylcholine-mediated relaxation in rat thoracic aorta is enhanced following
      acute exposure to physiological concentrations of 17beta-estradiol.
AB  - We investigated the effects of short-term exposure to low concentrations of
      17beta-estradiol on vasorelaxation using an in vitro rat thoracic aortic ring
      preparation. Supraphysiological levels of 17beta-estradiol directly relaxed
      phenylephrine-contracted rings. Although acute incubation (20 min) with 1-100 nM
      of the female sex hormone did not have any significant effect on phenylephrine
      contracted rings, relaxation evoked by acetylcholine was significantly
      potentiated. In contrast, calcium ionophore A23187-elicited endothelium-dependent
      relaxation as well as cromakalim- and sodium nitroprusside-mediated endothelium
      independent relaxation was unchanged following the same regime with 17beta
      estradiol. These results demonstrate that short-term treatment with
      physiologically relevant levels of 17beta-estradiol, which on their own have no
      effect, enhances endothelium-dependent relaxation by acetylcholine. The vascular
      effects observed herein may partly account for some of the improved acute
      vasodilatory responses reported with 17beta-estradiol on blood flow in humans.

PMID- 10888229
TI  - The effects of high-dose epinephrine combined with isoprenaline on isolated
      rabbit heart and cardiomyocytes after cardioversion of ventricular fibrillation.
AB  - The effects of high-dose epinephrine (HDE) combined with isoprenaline (Iso) on
      myocardial hemodynamics of isolated rabbit heart were studied. The
      electrophysiology and L-type Ca2+ channel of single ventricular myocyte after
      cardioversion of ventricular fibrillation were determined. The results suggest
      that parameters of hemodynamics were significantly enhanced by HDE+Iso than that
      of HDE (p < 0.01). The OS and Vmax of HDE+Iso increased 83.7 and 10.15%
      respectively compared to HDE alone. The APF of HDE+Iso is much more rapid than
      that of HDE (138.38 +/- 9.96 vs. 55.58 +/- 8.63 min(-1), p < 0.001). The APD50
      and APD90 of HDE+Iso were significantly decreased; HR was increased (134.16 +/-
      1.48 vs 62.20 +/- 6.25 min(-1)); and the amplitude current of through L-type Ca2+
      channel was reduced but was significantly higher than the control. We conclude
      that HDE+Iso can improve the hemodynamics and improve electrophysiology of
      cardiomyocytes after cardioversion of ventricular fibrillation which is likely
      interrelated with I(Ca). The combined use of epinephrine and isoprenaline for
      cardiopulmonary resuscitation of primary ventricular fibrillation may be
      beneficial when employed in clinical situations.

PMID- 10888230
TI  - Adriamycin-induced heart failure: mechanism and modulation.
AB  - Adriamycin (doxorubicin) is one of the most effective chemotherapeutic agents
      against a variety of cancers, but its usefulness is seriously curtailed by the
      risk of developing heart failure. Available laboratory evidence suggests that an
      increase in oxidative stress, brought about by increased free radical production
      and decreased myocardial endogenous antioxidants, plays an important role in the
      pathogenesis of heart failure. Adriamycin-induced apoptosis and hyperlipidemia
      may also be involved in the process. Probucol, a lipid-lowering drug and an
      antioxidant, completely prevents the occurrence of heart failure by reducing
      oxidative stress as well as by the modulation of apoptosis and high lipid
      concentrations. Thus, combined therapy with adriamycin and probucol has a high
      potential for optimizing the treatment of cancer patients.

PMID- 10888231
TI  - Modification of heart sarcolemmal Na+/K+-ATPase activity during development of
      the calcium paradox.
AB  - This study examined the status of sarcolemmal Na+/K+-ATPase activity in rat heart
      under conditions of Ca2+-paradox to explore the existence of a relationship
      between changes in Na+/K+-pump function and myocardial Na+ as well as K+ content.
      One min of reperfusion with Ca2+ after 5 min of Ca2+-free perfusion reduced
      Na+/K+-ATPase activity in the isolated heart by 53% while Mg2+-ATPase, another
      sarcolemmal bound enzyme, retained 74% of its control activity. These changes in
      sarcolemmal ATPase activities were dependent on the duration and Ca2+
      concentration of the initial perfusion and subsequent reperfusion periods;
      however, the Na+/K+-ATPase activity was consistently more depressed than Mg2+
      ATPase activity under all conditions. The depression in both enzyme activities
      was associated with a reduction in Vmax without any changes in Km values. Low Na+
      perfusion and hypothermia, which protect the isolated heart from the Ca2+
      paradox, also prevented reperfusion-induced enzyme alterations. A significant
      relationship emerged upon comparison of the changes in myocardial Na+ and K+
      content to Na+/K+-ATPase activity under identical conditions. At least 60% of the
      control enzyme activity was necessary to maintain normal cation gradients.
      Depression of the Na+/K+-ATPase activity by 60-65% resulted in a marked increase
      and decrease in intracellular Na+ and K+ content, respectively. These results
      suggest that changes in myocardial Na+ and K+ content during Ca2+-paradox are
      related to activity of the Na+/K+-pump; the impaired Na+/K+-ATPase activity may
      lead to augmentation of Ca2+-overload via an enhancement of the Na+/Ca2+-exchange
      system.

PMID- 10888232
TI  - Phosphatidylcholine metabolism in human endothelial cells: modulation by
      phosphocholine.
AB  - Phosphatidylcholine is the principal phospholipid in mammalian tissues, and a
      major source for the production of arachidonic acid. In this study, the effect of
      exogenous phosphocholine, a precursor of phosphatidylcholine biosynthesis, on the
      metabolism of phosphatidylcholine in human umbilical vein endothelial cells was
      investigated. Incubation of endothelial cells with exogenous phosphocholine at
      concentrations of 1 to 5 mM was found to inhibit choline uptake and its
      subsequent incorporation into phosphatidylcholine. Phosphocholine appeared to
      inhibit choline uptake in a competitive manner. Since phosphatidylcholine is
      metabolized mainly by the action of phospholipase A2, with the release of
      arachidonic acid and other fatty acids, the effect of phosphocholine on
      arachidonic acid release in endothelial cells was also examined. The induction of
      arachidonic acid release by ATP was enhanced in cells treated with 1 mM
      phosphocholine. In vitro assays of phospholipase A2 activity in cells incubated
      with phosphocholine, however, did not produced any significant change in the
      activity of this enzyme. The results of this study show that phosphocholine
      modulates the biosynthesis and catabolism of phosphatidylcholine in an indirect
      manner.

PMID- 10888233
TI  - The expression of insulin-like growth factor binding proteins in human
      hepatocellular carcinoma.
AB  - Insulin-like growth factors (IGF), IGF receptors and IGF binding proteins
      (IGFBPs) play an important role in cell growth and differentiation. The liver is
      the major source of IGF-1 and at least two IGFBPs (IGFBP-1 and IGFBP-3). IGFBPs
      most often serve to attenuate the effects of IGF at the receptor level and
      thereby limit IGF-induced cell growth and differentiation. Although changes in
      IGFBP expression have been described during controlled liver growth such as
      hepatic regeneration following partial hepatectomy, there is limited knowledge of
      IGFBPs gene expression in uncontrolled growth or hepatocellular carcinoma. In the
      present study, we employed Northern blotting techniques to document the
      expression of IGFBP-1, 3 and 4 in normal human livers, cirrhotic and
      hepatocellular carcinoma tissues. The results revealed no differences in IGFBP-1,
      3 and 4 mRNA levels between normal and cirrhotic tissues. However, the expression
      of all three IGFBPs mRNA were significantly down regulated in hepatocellular
      carcinoma tissues. These findings are in keeping with IGFBPs playing an important
      inhibitory role in the development and/or growth of hepatocellular carcinoma in
      humans.

PMID- 10888234
TI  - GABA and hepatocellular carcinoma.
AB  - Data derived from models of hepatic regeneration indicate that transient,
      reciprocal changes in polyamines, potent growth promoters, and gamma aminobutyric
      acid (GABA), an amino acid neurotransmitter with growth inhibitory properties,
      play important roles in enhancing and inhibiting respectively regulated
      hepatocyte proliferation. Based on these findings and supportive data derived
      from studies of human carcinoma tissues and malignant cell lines we propose that
      permanent increases in polyamine and decreases in GABAergic activity act in
      concert to contribute to the pathogenesis of hepatocellular carcinoma.

PMID- 10888235
TI  - The effects of acute ethanol exposure on inhibitors of hepatic regenerative
      activity in the rat.
AB  - The purpose of this study was to identify the mechanism(s) whereby acute ethanol
      exposure inhibits hepatic regenerative activity in the rat. Adult, male, Sprague
      Dawley rats (200-250 g) were randomized to receive either ethanol (1 g/kg i.p. q
      4 h) or an equal volume of saline (controls) for 24 h beginning 1 h prior to a
      70% partial hepatectomy (PHx). At 0, 3, 6, 12 and 24 h post-PHx, rats were
      sacrificed (N = 4-6/group), and the expression of the following genes associated
      with inhibition of hepatocyte proliferation were documented; p53, p21,
      transforming growth factor-beta1 (TGF-beta1) and gamma aminobutyric acid
      transport protein (GABA-TP). Inhibition of hepatic regenerative activity was
      confirmed by 3H-thymidine incorporation into hepatic DNA at 24 h post-PHx. The
      results of the study revealed that in ethanol-treated rats, DNA synthesis was
      inhibited by 37% when compared to saline-treated controls (p < 0.01). Regarding
      suppressor gene expression, both p21 and TGF-beta1 mRNA expression in ethanol
      treated rats were similar to those obtained in saline-treated controls. Although
      p53 mRNA expression differed in the two groups, in the ethanol-treated group, p53
      mRNA expression was decreased rather than increased (relative to controls) at 24
      h post-PHx, a finding not in keeping with inhibition of DNA synthesis. GABA-TP
      mRNA was strongly expressed prior to PHx in both ethanol- and saline-treated
      rats. Following PHx, GABA-TP mRNA expression decreased in both groups but
      remained low in the saline-treated group while returning to pre-PHx values in
      ethanol-treated rats. In summary, the results of this study indicate that the
      inhibitory effects of ethanol on hepatic regeneration are not associated with
      significant or the appropriate changes in mRNA expression of the p53, p21 or TGF
      beta1 suppressor genes. On the other hand, transcriptional changes in GABA-TP
      gene expression post-PHx are in keeping with an inhibitory effect of GABA on
      hepatic regeneration.

PMID- 10888236
TI  - Differential effects of chloroquine on cardiolipin biosynthesis in hepatocytes
      and H9c2 cardiac cells.
AB  - Chloroquine is a potent lysomotropic therapeutic agent used in the treatment of
      malaria. The mechanism of the chloroquine-mediated modulation of new cardiolipin
      biosynthesis in isolated rat liver hepatocytes and H9c2 cardiac myoblast cells
      was addressed in this study. Hepatocytes or H9c2 cells were incubated with [1,3
      (3)H]glycerol in the absence or presence of chloroquine and cardiolipin
      biosynthesis was examined. The presence of chloroquine in the incubation medium
      of hepatocytes resulted in a rapid accumulation of radioactivity in cardiolipin
      indicating an elevated de novo biosynthesis. In contrast, chloroquine caused a
      reduction in radioactivity incorporated into cardiolipin in H9c2 cells. The
      presence of brefeldin A, colchicine or 3-methyladenine did not effect
      radioactivity incorporated into cardiolipin nor the chloroquine-mediated
      stimulation of cardiolipin biosynthesis in hepatocytes indicating that vesicular
      transport, cytoskeletal elements or increased autophagy were not involved in de
      novo cardiolipin biosynthesis induced by chloroquine. The addition of chloroquine
      to isolated rat liver membrane fractions did not affect the activity of the
      enzymes of de novo cardiolipin biosynthesis but resulted in an inhibition of
      mitochondrial cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol hydrolase activity.
      The mechanism for the reduction in cardiolipin biosynthesis in H9c2 cells was a
      chloroquine-mediated inhibition of glycerol uptake and this did not involve
      impairment of lysosomal function. The kinetics of the chloroquine-mediated
      inhibition of glycerol uptake indicated the presence of a glycerol transporter in
      H9c2 cells. The results of this study clearly indicate that chloroquine has
      markedly different effects on glycerol uptake and cardiolipin biosynthesis in
      hepatocytes and H9c2 cardiac cells.

PMID- 10888237
TI  - The effect of fenofibrate treatment on endothelium-dependent relaxation induced
      by oxidative modified low density lipoprotein from hyperlipidemic patients.
AB  - The objective of the research project was to investigate whether fenofibrate
      treatment may alter the biochemical content of the oxidized LDL and consequently
      its ability to impair the endothelium-dependent relaxation in hyperlipidemic
      patients. We hypothesized that fenofibrate treatment of hyperlipidemic patients
      may attenuate the ability of their oxidized LDL to impair the endothelium
      dependent relaxation of the blood vessels as a consequence of fenofibrate-induced
      changes to the content and composition of lysoPC in the LDL molecule.
      Hyperlipidemic patients (Type IIb and Type IV) were recruited from the Lipid
      Clinic, HSC, Winnipeg, Canada, for this study. A blood sample was taken
      immediately after the recruitment, a second sample was taken after 6 weeks of
      dietary treatment, and a third sample was taken after 8 weeks of fenofibrate
      treatment. LDL was isolated from the plasma and oxidized by copper sulfate.
      Fenofibrate was shown to be highly effect in the reduction of total cholesterol,
      LDL cholesterol and triglycerides in these patients. Fenofibrate treatment also
      caused the attenuation of impairment of endothelium-dependent relaxation by the
      oxidized LDL from these patients. A slight reduction of lysophosphatidylcholine
      level was also found in the oxidized LDL of the fenofibrate treated patients,
      relative to LDL isolated after dietary treatment. In addition there were no
      changes in the fatty acid levels of the lysophosphatidylcholine isolated from
      LDL. Taken together, our results suggest that while the reduced
      lysophosphatidylcholine levels may contribute to the attenuated impairment of the
      endothelium-dependent relaxation of the aortic ring, other unidentified factors
      impacted by fenofibrate are likely to contribute to the attenuated effects.

PMID- 10888238
TI  - Oxidative modification of lipoproteins in hypertriglyceridemic patients and
      hypercholesterolemic rabbits in vivo.
AB  - Many lines of evidence suggest that LDL is oxidized in vivo and that Ox-LDL is
      present in the artery wall. But the oxidation of VLDL and HDL in vivo has not yet
      been reported. In this study, the oxidative modification of serum LDL, VLDL, and
      HDL in patients with endogenous hypertriglyceridemia (HTG) and in serum of
      rabbits fed on high cholesterol diet were made. The serum LDL, VLDL and HDL were
      isolated by the density gradient ultracentrifugation. The oxidative modification
      of LDL, VLDL and HDL were identified by agarose eletrophoresis, absorbance at 234
      nm and fluorescence of TBARS. The results showed that serum TC, TG and TBARS in
      the HTG group (n = 25) and in rabbits fed with a high fat diet (for 12 weeks, n =
      8) were significantly higher than those of the corresponding control groups
      (normal subjects, n = 25; rabbits fed with a normal diet, n = 8; p < 0.01). The
      electrophoretic mobilities of LDL, VLDL and HDL were increased when compared with
      the controls, and absorbance at 234 nm and TBARS of LDL, VLDL and HDL in the HTG
      group and in the high fat diet rabbits were significantly higher than those of
      the controls (p < 0.01). These results suggest that not only LDL but also VLDL
      and HDL were oxidatively modified in vivo in the patients with HTG and in the
      rabbits fed with a high cholesterol diet.

PMID- 10888239
TI  - Overexpression of SERCA2 Atpase in vascular smooth muscle cells treated with
      oxidized low density lipoprotein.
AB  - Oxidized low density lipoprotein (oxLDL) has been identified as a potentially
      important atherogenic factor. Atherosclerosis is characterized by the
      accumulation of lipid and calcium in the vascular wall. OxLDL plays a significant
      role in altering calcium homeostasis within different cell types. In our previous
      study, chronic treatment of vascular smooth muscle cells (VSMC) with oxLDL
      depressed Ca2+(i) homeostasis and altered two Ca2+ release mechanisms in these
      cells (IP3 and ryanodine sensitive channels). The purpose of the present study
      was to further define the effects of chronic treatment with oxLDL on the smooth
      muscle sarcoplasmic reticulum (SR) Ca2+ pump. One of the primary Ca2+ uptake
      mechanisms in VSMC is through the SERCA2 ATPase calcium pump in the sarcoplasmic
      reticulum. VSMC were chronically treated with 0.005-0.1 mg/ml oxLDL for up to 6
      days in culture. Cells treated with oxLDL showed a significant increase in the
      total SERCA2 ATPase content. These changes were observed on both Western blot and
      immunocytochemical analysis. This increase in SERCA2 ATPase is in striking
      contrast to a significant decrease in the density of IP3 and ryanodine receptors
      in VSMC as the result of chronic treatment with oxLDL. This response may suggest
      a specific adaptive mechanism that the pump undergoes to attempt to maintain Ca2+
      homeostasis in VSMC chronically exposed to atherogenic oxLDL.

PMID- 10888240
TI  - Atherosclerosis risk factors: the possible role of homocysteine.
AB  - Atherosclerosis is the leading cause of death in North America. It is
      characterized by thickening of the coronary artery wall by the formation of
      plaques, resulting in reduced blood flow. Plaque rupture and the consequent
      thrombosis may lead to sudden blockage of arteries and causing stroke and heart
      attack. In the last several decades, more than 250 factors associated with the
      development of coronary artery disease have been identified. Recently, a
      relationship between atherosclerosis and elevated homocysteine level in the blood
      has been established. The mechanism for the production of atherosclerosis by
      homocysteine has been investigated. When human hepatoma cells (HepG2) were
      incubated with 4 mM homocysteine, enhancements in the production of cholesterol
      and secretion of apolipoprotein B-100 were observed. The stimulatory effect on
      cholesterol synthesis was mediated via the enhancement of HMG-CoA reductase,
      which catalyzes the rate-limiting step in cholesterol biosynthesis. Cholesterol
      appears to play an important role in the regulation of apoB-100 secretion by
      hepatocytes. It is plausible that the increase in apoB secretion was caused by
      the elevated cholesterol level induced by homocysteine. The ability of
      homocysteine to produce a higher amount of cholesterol and promote the secretion
      of apoB would provide a plausible mechanism for the observed relationship between
      hyperhomocysteinemia and the development of atherogenesis and coronary artery
      disease.

PMID- 10888241
TI  - Evaluation of a new apolipoprotein(a) isoform-independent assay for serum
      Lipoprotein(a).
AB  - The risk factor, Lipoprotein(a), [(Lp(a)], has been measured in numerous clinical
      studies by a variety of immunochemical assay methods. It is becoming apparent
      that for many of these assays antibody specificity towards the apolipoprotein(a)
      [apo(a)] repetitive component [the kringle 4-type 2 repeats] and apo(a) size
      heterogeneity can significantly affect the accuracy of serum Lp(a) measurements.
      To address this issue, we investigated whether our current in house Lp(a)
      [Mercodia] assay showed such bias compared to a recently available assay [Apo
      Tek], claiming to possess superior capability for isoform-independent measurement
      of Lp(a). Levels of Lipoprotein(a) by both Apo-Tek and Mercodia assays correlated
      inversely with apo(a) isoform sizes. No significant differences were observed
      between assays in ranges of Lp(a) concentration within each isoform group. The
      Mercodia assay exhibited similar isoform-independent behaviour to that of Apo-Tek
      for the quantitation of serum Lipoprotein(a). Essentially identical results were
      obtained by the two methods, suggesting that Mercodia assay's capture monoclonal
      antibody also (as is the case for Apo-Tek) does not recognize the kringle 4-type
      2 repetitive domain of apo(a). Correlation of Lp(a) concentrations in patient
      specimens between Apo-Tek and Mercodia assays showed good agreement, although an
      overall higher degree of imprecision and non-linearity was noted for the Apo-Tek
      procedure. A change-over to the Apo-Tek assay would therefore not improve on our
      current assessment of risk contribution from Lp(a) for atherosclerotic vascular
      disease in individuals with measurable levels of circulating Lipoprotein(a).

PMID- 10888242
TI  - Induction of cardiac fibrosis by aldosterone.
AB  - An intracardiac aldosterone system which responds to short- and long-term
      physiological stimuli has been described. This cardiac generated aldosterone has
      possibly autocrine or paracrine actions. Normal cardiac tissue contains
      mineralocorticoid receptors (MR) and cardiac high affinity MR are localized in
      cardiac myocytes and endothelial cells. Data concerning the presence of MR in
      cardiac fibroblasts are, however, controversial. MR are not specific for
      aldosterone but they also bind glucocorticoids. Cardiac fibroblasts however
      contain the enzyme 11beta-hydroxy-steroid dehydrogenase II which converts these
      glucocorticoids to inactive metabolites. Discordant findings on the in vitro
      effect of aldosterone on the collagen synthesis in cardiac fibroblasts are
      reported and can at least partly attributed to the presence of various
      fibroblasts phenotypes. During chronic aldosterone infusion in uninephrectomized
      rats on a high-salt diet, a marked accumulation of interstitial and to a lesser
      extent perivascular collagen occurs in the heart in both ventricles. This cardiac
      fibrosis in this aldosteronism model is prevented by spironolactone. This effect
      of aldosterone is crucially dependent on the salt status of the rat. Indeed, rats
      on a restricted salt intake infused with aldosterone had no cardiac fibrosis
      above control levels. During the continuous infusion of aldosterone in the rat
      the appearance of fibrosis was delayed and starts 4 weeks after the beginning of
      the infusion which argues against a direct effect of aldosterone. The mechanism
      of aldosterone-salt induced cardiac fibrosis possibly involves angiotensin II
      acting through upregulated AT1 receptors and the cardiac AT1 receptor is the
      target for aldosterone. An accumulation of collagen in the heart has also been
      found in patients with adrenal adenomas and during chronic activation of the
      renin-angiotensin-aldosterone system such as in surgically induced unilateral
      renal ischemia, unilateral renal artery banding or renovascular hypertension.
      Spironolactone prevents aortic collagen accumulation in spontaneously
      hypertensive rats. In patients with stable chronic heart failure spironolactone
      treatment in addition to diuretics and angiotensin-converting enzyme (ACE)
      inhibition reduced circulating levels of procollagen type III N-terminal
      aminopeptide. Also, in the Randomized Aldactone Evaluation Study spironolactone
      coadministered with conventional therapy of ACE inhibitors, loop diuretics and
      digitalis in patients with symptomatic heart failure defined as NYHA classes III
      IV reduces total mortality by 30%.

PMID- 10888243
TI  - Apoptosis in rat cardiac myocytes induced by Fas ligand: priming for Fas-mediated
      apoptosis with doxorubicin.
AB  - Fas/Fas ligand (FasL) is well known for its role in delivering apoptotic signals;
      however, it is unclear whether FasL can mediate apoptosis in cardiomyocytes. We
      hypothesized that apoptosis via Fas/FasL system may be augmented in damaged
      cardiomyocytes. To determine whether FasL mediates cardiomyocyte apoptosis,
      recombinant FasL (rFasL) was added to the culture of neonatal rat ventricular
      myocytes pretreated with and without doxorubicin. Without doxorubicin, high dose
      of rFasL caused an increase in TUNEL-positive cardiomyocytes and a mild decrease
      in MTT activities. When cardiomyocytes were pretreated with doxorubicin (0.5
      microM), rFasL dramatically augmented TUNEL-positive cardiomyocytes in a
      concentration-dependent manner, which was accompanied with nuclear
      fragmentations. The rFasL also caused a concentration-dependent reduction in MTT
      activities in cardiomyocytes. The rFasL-induced caspase-8 activity was greatly
      facilitated by pretreatment of doxorubicin. TUNEL-positive nuclei with rFasL was
      inhibited by Fas-Fc, neutralizing agent of rFasL, and Z-IETD-FMK, caspase-8
      inhibitor. Fas mRNA transcript by RT-PCR was up-regulated in cardiomyocytes with
      doxorubicin. We conclude that FasL can induce cardiomyocyte apoptosis
      particularly when cardiomyocyte becomes susceptible for Fas-mediated apoptosis.

PMID- 10888244
TI  - Glycolysis supports calcium uptake by the sarcoplasmic reticulum in skinned
      ventricular fibres of mice deficient in mitochondrial and cytosolic creatine
      kinase.
AB  - Several works have shown the importance of the creatine kinase (CK) system for
      cardiac energetics and Ca2+ homeostasis. Nevertheless, CK-deficient mice have
      cardiac function close to normal, at least under conditions of low or moderate
      workload. To characterize possible adaptive changes of the sarcoplasmic reticulum
      (SR) and potential role of glycolytic support in cardiac contractility we used
      the skinned fibre technique to study properties of the SR and myofibrils, in
      control and muscle-type homodimer (MM-/mitochondrial-CK)-deficient mice. In
      control fibres, SR Ca2+ loading with ATP and phosphocreatine (solution PL) was
      significantly better than loading with ATP alone (solution AL), as determined by
      analysis of caffeine-induced tension transients. Loading in the presence of ATP
      and glycolytic intermediates (solution GL) was not significantly different from
      solution PL. These data indicate that Ca2+ uptake by the SR in situ depends on a
      local ATP:ADP ratio that is controlled by both CK and glycolytic enzymes. In CK
      deficient mice, Ca2+ loading was impaired in solution PL due to the absence of
      CK. In solution GL, loading was significantly increased, such that calculated
      Ca2+ release parameters were normalized to those in control fibres in solution
      PL. In CK-deficient mice, fibre kinetic parameters of tension recovery were
      impaired after quick stretch in solution PL and were not improved in solution GL.
      These results show that in CK-deficient mice, at least under basal conditions,
      glycolysis can replace the CK system in fueling the SR Ca2+ ATPase, but not the
      myosin ATPase, and may in part explain the limited phenotypic alterations seen in
      the hearts of these mice.

PMID- 10888245
TI  - Exercise training enhances glycolytic and oxidative enzymes in canine ventricular
      myocardium.
AB  - Aerobic exercise training evokes adaptations in the myocardial contractile
      machinery that enhance cardiac functional capacity; in comparison, the effects of
      training on the myocardium's energy generating pathways are less well
      characterized. This study tested the hypothesis that aerobic exercise training
      can increase the capacities of the major pathways of intermediary metabolism in
      canine myocardium. Mongrel dogs were conditioned by a 9-week treadmill running
      program or cage rested for 4 weeks. Exercise conditioning was evidenced by 26%
      and 22% decreases (P<0.05) in respective heart rates at rest and during
      submaximal exercise and by a 40% increase (P<0.05) in citrate synthase (CS)
      activity of the vastus lateralis. Glycolytic, TCA cycle, and beta-oxidative
      enzymes were assayed in myocardial extracts at 37 degrees C. Relative to
      sedentary controls, training increased glyceraldehyde 3-phosphate dehydrogenase
      (GAPDH) activity by 49% in left and 33% in right ventricle, and pyruvate kinase,
      CS, and 3-hydroxyacyl CoA dehydrogenase (HADH) activities by 74%, 91%, and 77%,
      respectively, in left ventricle (P<0.05). Immunoblotting further confirmed that
      training increased left ventricular contents of CS and GAPDH. Other measured
      enzymes (hexokinase, phosphofructokinase, lactate dehydrogenase, alpha
      ketoglutarate dehydrogenase, malate dehydrogenase) were not altered by training
      in either ventricle. Kinetic analyses revealed increased maximum rates but
      unaltered substrate affinities of GAPDH, CS and HADH following training. Thus,
      aerobic exercise training augments the intermediary metabolic capacity of canine
      myocardium by selectively increasing the concentrations of regulatory enzymes of
      glycolysis and oxidative metabolism.

PMID- 10888247
TI  - Calcium and osmotic regulation of the Na+/H+ exchanger in neonatal ventricular
      myocytes.
AB  - Intracellular pH regulation in primary cultures of neonatal cardiac myocytes has
      been characterized. Myocytes were exposed to hyperosmolar solutions to examine
      the effects on pH regulation by the Na+/H+ exchanger. Exposure to 100 mM NaCl,
      sorbitol, N-methyl-D-glucamine, or choline chloride all caused significant
      increases in steady state pHi in myocytes. Omission of extracellular calcium or
      administration of calmodulin antagonists reduced the osmotic activation of the
      exchanger. The myosin light-chain inhibitor ML-7 completely blocked osmotic
      activation of the exchanger suggesting that myosin light-chain kinase is involved
      in osmotic activation of the exchanger in the myocardium. The calmodulin
      dependent protein kinase II inhibitor KN-93 inhibited the rate of recovery from
      an acute acid load as did trifluoperazine (TFP) and the calmodulin blocker W7, [N
      (6-aminohexyl)-5-chloro-1-naphthalenesulfonamide]. Addition of the calcium
      ionophore ionomycin caused a large increase in resting pHi in isolated myocytes.
      However, this effect was largely resistant to HMA (5-(N,N-hexamethylene)
      amiloride) indicating that an alternative mechanism of pHi regulation is
      responsible. The results demonstrate that the Na+/H+ exchanger of the neonatal
      myocardium is responsive to calcium and osmotically responsive pathways and that
      myosin light-chain kinase is a key protein involved in mediating the osmotic
      response.

PMID- 10888248
TI  - Activation of TxA2/PGH2 receptors and protein kinase C contribute to coronary
      dysfunction in superoxide treated rat hearts.
AB  - We have previously shown that superoxide anion (O2-) stimulates the release of
      vasoconstrictor prostanoids and induces a prolonged rise in coronary perfusion
      pressure (CPP) that persists even after removal of O2-. In this study, we tested
      the hypothesis that the increased CPP is mediated by activation of TxA2/ PGH2
      (TP) receptors and protein kinase C (PKC)-dependent mechanisms. In Langendorff
      perfused rat hearts, O2- was applied for 15 min and then washed out over a period
      of 20 min. Application of O2- increased the release of vasoconstrictive (TxA2 and
      PGF2alpha) and decreased vasodilating (PGI2 and PGE2) prostanoids. Although
      indomethacin (10 microM), a cyclooxygenase inhibitor, attenuated the rise in CPP
      during O2- perfusion, the increase was not completely blocked. OKY 046Na (10
      microM), a thromboxane synthase inhibitor, had no effect on O2--induced increases
      in CPP, whereas ONO 3708 (10 microM), a TP receptor antagonist, suppressed this
      effect. PKC activity was also elevated by more than 50% by O2- perfusion. CPP
      typically increased throughout the O2- wash-out. This post-O2- vasoconstriction
      was not inhibited by indomethacin, nitroglycerin or nitrendipine. In contrast,
      ONO 3708 (10 microM) and two PKC inhibitors, staurosporine (10 nM) and calphostin
      C (100 nM), completely blocked the rise in CPP, and even elicited vasodilation.
      PDBu enhanced the post-O2- vasoconstriction. We conclude that O2--induced
      coronary vasoconstriction is initially mediated by TP receptors, but activation
      of PKC sustains the response.

PMID- 10888246
TI  - Modulation of neutrophil migration and superoxide anion release by metoprolol.
AB  - In addition to having anti-sympathotonic effects, beta-blockers are thought to
      have some adrenoceptor-independent properties. Such ancillary effects are
      described for carvedilol acting as oxygen radical scavenger and for propranolol
      which blocks protein kinase C and phosphatidate phosphohydrolase. The goal of our
      in vitro experiments was to identify ancillary effects of the widely used beta
      blockers metoprolol and atenolol in neutrophils. Neutrophil chemotaxis was tested
      using the leading front assay in a modified Boyden microchemotaxis chamber.
      Respiratory burst activity was detected fluorometrically. Inhibition of protein
      kinase C activity was tested with purified alpha-, beta- and gamma-isoenzyme
      preparation. Metoprolol dose-dependently inhibited formyl peptide-stimulated
      neutrophil chemotaxis and formylpeptide- and phorbol myristate acetate-triggered
      oxygen free radical production. These actions were not affected by the
      competitive presence of the beta-receptor agonist, orciprenaline. Effects of
      metoprolol, as well as of propranolol, and the signaling enzyme blockers were
      strongly time dependent. Propranolol mimicked effects of staurosporine on
      respiratory burst, whereas the effects of metoprolol were similar to
      bisindolylmaleimide, a specific protein kinase C blocker. Atenolol, a hydrophilic
      beta-blocker, neither affected neutrophil chemotaxis nor respiratory burst. In a
      cell-free system, metoprolol did not interfere with the activity of the purified
      protein kinase C alpha-, beta- and gamma-isoenzymes. Adrenoceptor-independent
      inhibition of neutrophil chemotaxis and free radical production is a novel mode
      of action of metoprolol that may be relevant for beneficial effects ot the beta
      blocker in heart failure and endothelial preconditioning.

PMID- 10888249
TI  - Requirement of activation of the extracellular signal-regulated kinase cascade in
      myocardial cell hypertrophy.
AB  - The signal transduction mechanisms mediating hypertrophic responses in myocardial
      cells (MCs) remain uncertain. We investigated the role of the extracellular
      signal-regulated kinase (ERK) cascade in myocardial cell hypertrophy by the
      strategy of using the adenovirus-mediated overexpression of mitogen-activated
      protein kinase (MAPK)/ERK kinase (MEK), which is the upstream activator of ERK.
      We generated recombinant adenoviruses expressing constitutively active MEK1 (MEK1
      EE) and dominant negative MEK1 (MEK1 DN). Overexpression of MEK1 EE in MCs
      activated ERK1/2 and subsequently induced atrial natriuretic peptide (ANP) mRNA
      expression. In addition, MEK1 EE overexpression resulted in an increase in cell
      size and sarcomeric reorganization. In contrast, overexpression of MEK1 DN in MCs
      inhibited endothelin-1 (ET-1)-, phenylephrine (PE)-, leukemia inhibitory factor
      (LIF)-, isoproterenol (ISP)-, and mechanical stretch-induced ERK activation and
      ANP mRNA expression. MEK1 DN overexpression inhibited ET-1-, PE-, LIF-, and ISP
      induced increases in cell size and sarcomeric reorganization. Consistent with the
      observed effects on cellular morphology, overexpression of MEK1 EE resulted in an
      increase in amino acid incorporation, while overexpression of MEK1 DN inhibited
      ET-1-, PE-, LIF-, ISP-, and mechanical stretch-induced increases in amino acid
      incorporation. These results indicate that the ERK cascade plays an important
      role in the signaling pathway leading to the development of myocardial cell
      hypertrophy.

PMID- 10888250
TI  - Ischemic preconditioning: a potential role for constitutive low molecular weight
      stress protein translocation and phosphorylation?
AB  - We have investigated whether translocation of constitutive low molecular weight
      stress proteins (alphaB-crystallin and HSP27) to the myofilament/cytoskeletal
      compartment occurs during ischemic preconditioning and assessed if this is
      causally associated with cardioprotection. Triton-insoluble preparations from
      fresh or aerobically perfused rat hearts (n=4/group) contained relatively little
      alphaB-crystallin (96 +/- 43 and 43 +/- 36 units respectively) or HSP27 (177 +/-
      32 and 101 +/- 26 units respectively). Three preconditioning cycles of (5 min
      ischemia + 5 min reperfusion) increased the Triton-insoluble crystallin to 864 +/
      61 units (P<0.05) and HSP27 to 1353 +/- 53 units (P<0.05). Two hours of aerobic
      perfusion following the preconditioning protocol resulted the return of alphaB
      crystallin and HSP27 to near control levels (189 +/- 14 units and 252 +/- 24
      units, respectively). Stress protein translocation, comparable to that achieved
      by the IPC protocol was induced by aerobic perfusion with hypercarbic (pH 6.8)
      perfusion. Thus, three cycles of 5 min hypercarbia + 5 min normocarbia increased
      alphaB-crystallin to 628 +/- 30 units (P<0.05) and HSP27 to 1353 +/- 53 units. In
      parallel functional studies, the recovery of LVDP after 35 min ischemia and 60
      min of reperfusion was 43 +/- 7% in the ischemic control group, 61 +/- 3%
      (P<0.05) in the preconditioned group and 42 +/- 6% in the hypercarbic group.
      Thus, translocation of alphaB-crystallin and/or is not of-itself sufficient to
      induce cardioprotection. Using a phospho-specific antibody, we have demonstrated
      that preconditioning not only translocates alphaB-crystallin but also increases
      its phosphorylation at Ser-59 by 9.7-fold compared to aerobic controls (1616 +/-
      402 v 166 +/- 28 units respectively). In contrast, hypercarbia while eliciting a
      comparable translocation, failed to alter the phosphorylation state of alphaB
      crystallin. Preconditioning-induced phosphorylation was significantly attenuated
      by 50 microM genistein (by 61%), 10 microM SB203580 (by 91%) and 10 microM
      bisindolylmaleimide (by 68%), but not by 10 microM PD98059 (by 4%). Our findings
      are consistent with the possibility that ischemic preconditioning may be mediated
      by phosphorylation and translocation of constitutive low molecular weight stress
      proteins, particularly alphaB-crystallin.

PMID- 10888251
TI  - L-type Ca2+ channel alpha 1c subunit isoform switching in failing human
      ventricular myocardium.
AB  - The objectives of this study were to determine the relative abundance of the L
      type Ca channel alpha 1c IVS3 isoforms that result from alternative splicing in
      normal human ventricular myocytes and to measure the changes in isoform
      expression in end stage heart failure. METHODS: mRNA was isolated from left
      ventricular tissue and myocytes from non-failing and failing human hearts. RT-PCR
      with isoform-specific primers was used to obtain cDNAs that were then mutated for
      use in competitive PCR reactions. An RNase protection assay was also used to
      confirm the presence of one of the novel isoforms. RESULTS: Four different alpha
      1c IVS3 isoforms were found in non-failing human ventricular myocytes using RT
      PCR. Two isoforms contained exon 31 (termed IVS3A isoforms) and two isoforms
      contained exon 32 (termed IVS3B isoforms). One of these isoforms has not been
      observed previously and contains exon 31 and all but the last six base pairs of
      exon 32. In non-failing human ventricular myocytes the IVS3A isoform is 2.5 times
      more abundant than the IVS3B isoform. There were significant changes in the
      relative abundance of these isoforms in failing hearts, with the IVS3B isoform
      being twice as abundant as the IVS3A isoform. All isoforms were confirmed by
      RNase protection analysis. CONCLUSIONS: These experiments show that there are at
      least four L-type Ca channel mRNA isoforms in the normal human heart and that the
      relative abundance of these isoforms changes significantly in heart failure.
      These alpha 1c isoform changes in heart failure are associated with dysfunctional
      electromechanical disturbances, but the specific physiological role of each L
      type Ca channel isoform in normal and failing hearts needs to be defined.

PMID- 10888252
TI  - Streptozotocin-induced changes in cardiac gene expression in the absence of
      severe contractile dysfunction.
AB  - Diabetes mellitus alters energy substrate metabolism and gene expression in the
      heart. It is not known whether the changes in gene expression are an adaptive or
      maladaptive process. To answer this question, we determined both the time-course
      and the extent of the alteration of gene expression induced by insulin-deficient
      diabetes. Transcript analysis with real-time quantitative polymerase chain
      reaction (PCR) was performed in rat hearts 1 week (acute group) or 6 months
      (chronic group) after administration of streptozotocin (55 mg/kg). In the acute
      group, insulin-dependent diabetes induced a 55-70% decrease of both glucose
      transporter 1 (GLUT1) and GLUT4 transcripts, a slight decrease of liver-specific
      carnitine palmitoyltransferase I (CPT I), and no change in muscle-specific CPT I.
      The uncoupling protein UCP-3 increased three-fold, with no change in UCP-2. These
      metabolic alterations were accompanied by an isoform switching from the normally
      expressed alpha myosin heavy chain (MHC) to the fetal isoform betaMHC mRNA, by a
      50% decrease of cardiac alpha-actin mRNA, a 30% decrease of the sarcoplasmic Ca++
      ATPase mRNA, and a 50% decrease of muscle creatine kinase (P<0.01 v controls).
      All genomic changes were also present in the chronic group. Genomic markers of
      ventricular dysfunction [tumor necrosis factor alpha (TNF-alpha), inducible
      nitric oxide synthase, cyclo-oxygenase-2] were not affected by chronic diabetes.
      In both groups, there were no changes in resting left ventricular function by
      echocardiography. CONCLUSION: The heart adapts to insulin-deficient diabetes by a
      rapid and simultaneous response of multiple genes involved in cardiac metabolism
      and function. This genomic adaptation resembles the adaptation of cardiac
      hypertrophy, remains stable over time, and does not lead to major contractile
      dysfunction.

PMID- 10888253
TI  - Altered balance between extracellular proteolysis and antiproteolysis is
      associated with adaptive coronary arteriogenesis.
AB  - To study the role of extracellular proteolysis and antiproteolysis during
      adaptive arteriogenesis (collateral vessel growth) we took 58 collaterals at
      various developmental stages from 14 dogs with chronic occlusion of the left
      circumflex coronary artery (LCx) by ameroid constrictor. Immunofluorescence and
      quantitative immunofluorescence with antibodies against alpha-smooth muscle
      actin, desmin, matrix metalloproteinases 2 (MMP-2), MMP-9, tissue inhibitor of
      metalloproteinases 1 (TIMP-1) and 2 (TIMP-2), urokinase-type plasminogen
      activator (u-PA) and its inhibitor-1 (PAI-1) were studied with confocal
      microscopy. Additionally, SDS-PAGE zymography was employed. We found that in
      normal coronary arteries, MMP-2, MMP-9 and PAI-1 were present in all layers of
      the wall in small amounts. TIMP-1 was found only in smooth muscle cells. In
      contrast, in growing collaterals, MMP-2 and MMP-9 were 3.4-fold and 4.1-fold
      higher in the neointima than in the media respectively. TIMP-1 was 4.4-fold
      higher in the media over the growing neointima. Zymography showed MMP-2 and MMP-9
      activated. PAI-1 was increased, especially in the growing neointima where it was
      1.4-fold higher. In mature collaterals, MMP-2 and MMP-9 were downregulated in the
      neointima, 1.4-fold and 1.3-fold higher over the media. TIMP-1 was 1.4-fold
      increased in the neointima but PAI-1 was downregulated. Desmin and alpha-smooth
      muscle actin were significantly increased in the neointima compared to growing
      vessels. U-PA was moderately increased in growing vessels. TIMP-2 was not
      detectable in collaterals. We conclude that expression of MMP-2 and 9, TIMP-1 and
      PAI-1 showed a spatial and temporal pattern which is closely associated with the
      development of collateral vessels. The shift of the balance between proteolysis
      and antiproteolysis is regulated not only by MMPs and TIMP-1, but also by the PA
      PAI system.

PMID- 10888254
TI  - Expression and activity of protein kinase D/protein kinase C mu in myocardium:
      evidence for alpha1-adrenergic receptor- and protein kinase C-mediated
      regulation.
AB  - Protein kinase D (PKD), which is also known as protein kinase C (PKC) mu, is a
      novel serine/threonine kinase that can be activated in parallel with or
      downstream of PKC in various cell types, but its expression and regulation in
      myocardium have not been characterized. In the present study, two proteins of 110
      and 115 kDa were detected in rat ventricular myocardium using antibodies directed
      at the extreme N- or C-terminus of PKD. Both proteins were highly expressed in
      the fetal heart but showed a developmental decline in abundance. Fractionation
      studies showed that PKD was distributed between myocyte and non-myocyte fractions
      in the neonatal heart, but was found predominantly in the non-myocyte fraction in
      the adult heart. In cultured neonatal rat ventricular myocytes, an in vitro
      kinase assay revealed increased autophosphorylation of PKD (EC50 2.8 nM) in
      response to phorbol-12-myristate-13-acetate (PMA). Exposure to norepinephrine
      also induced a dose-dependent increase in PKD autophosphorylation (EC50 0.6
      microM). Pretreatment with the alpha1-adrenergic receptor (AR) antagonist
      prazosin blocked norepinephrine-induced PKD autophosphorylation, while the beta1
      AR antagonist atenolol had no effect, indicating that activation of PKD by
      norepinephrine occurred via the alpha1-AR. Involvement of the alpha1-AR was
      confirmed by exposure of myocytes to the alpha1-AR agonist phenylephrine, which
      induced a similar profile of PKD autophosphorylation to norepinephrine (EC50 0.6
      microM). The effects of both alpha1-AR stimulation and PMA on PKD
      autophosphorylation were mediated by PKC, since these effects could be attenuated
      by pretreatment of myocytes with the PKC inhibitor bisindolylmaleimide. These
      data show that PKD is expressed in rat ventricular myocardium, where its
      expression is subject to developmental control, and that PKD activity in
      ventricular myocytes is regulated through alpha1-AR- and PKC-mediated pathways.

PMID- 10888255
TI  - SR calcium depletion following reversal of the Na+/Ca2+-exchanger in rat
      ventricular myocytes.
AB  - We previously reported that cytosolic calcium transiently increases after
      reversal of the sarcolemmal Na+/Ca2+-exchanger. Calcium released from
      sarcoplasmic reticulum (SR) constituted the major part of this cytosolic
      transient. The aim of this study was to test whether reversal of the Na+/Ca2+
      exchanger affects SR calcium content, and whether altered SR calcium content is
      associated with direct triggering of SR calcium release or calcium release
      secondary to SR calcium overload. To this purpose we studied the change of SR
      calcium content after reversal of the Na+/Ca2+-exchanger and the dependence on
      the magnitude of change of its free energy (delta Gexch) in isolated rat
      ventricular myocytes. The Na+/Ca2+-exchanger was reversed by abrupt reduction of
      extracellular sodium ([Na+]o). The magnitude of change of deltaGexch was varied
      with [Na+]o. Cytosolic free calcium ([Ca2+]i) was measured with indo-1 and SR
      calcium content was estimated from the increase of [Ca2+]i after rapid cooling
      (RC). SR function was manipulated either by blockade of the SR Ca2+-ATPase with
      thapsigargin or by blockade of SR calcium release channels with tetracaine.
      Reversal of the Na+/Ca2+-exchanger caused a transient increase of [Ca2+]i of
      about 180 s duration with a time to peak of about 30 s. During the first 30 s
      rapid small amplitude cytosolic calcium fluctuations were superimposed on this
      transient. The magnitude of the response of [Ca2+]i to RC, during the course of
      the cytosolic [Ca2+]i transient, also transiently increased from 174 in control
      myocytes to 480 nmol/l at the time of the peak value. After correction of [Ca2+]i
      data for the fraction of mitochondrially compartmentalized indo-1 and
      mitochondrial calcium, total calcium released from SR after RC was calculated
      with the use of literature data on cytosolic calcium buffer capacity. Contrary to
      the measured RC-dependent increase of measured [Ca2+]i, after reversal of the
      Na+/Ca2+-exchanger, calculated total calcium released from SR transiently
      decreased. The extent of SR calcium depletion after reversal of the Na+/Ca2+
      exchanger increased with the magnitude of change of deltaGexch. Restitution of
      [Na+]o 30 s after reversal of the Na+/Ca2+-exchanger, greatly accelerated both
      recovery of [Ca2+]i and SR calcium content. Pretreatment of myocytes with
      thapsigargin caused almost entire depletion of SR and substantial reduction of
      the cytosolic transient of [Ca2+]i following reversal of the Na+/Ca2+-exchanger.
      Application of tetracaine hardly affected SR calcium content, but caused an
      increase of the SR calcium content following reversal of the Na+/Ca2+-exchanger,
      while the cytosolic transient increase of [Ca2+]i was substantially reduced. We
      conclude that reversal of the Na+/Ca2+-exchanger directly triggers SR calcium
      release and decreases SR calcium content in a deltaGexch dependent manner.

PMID- 10888256
TI  - Expression of genes encoding vascular endothelial growth factor and its Flk-1
      receptor in the chick embryonic heart.
AB  - Vascular endothelial growth factor (VEGF) is known to play an essential role in
      embryonic vascular development. The heart is one of the main organs that produce
      VEGF, but it is still unknown how expression of VEGF gene is regulated in
      embryonic cardiac myocytes. Thus, we cloned cDNAs encoding VEGF and its receptor
      (a KDR/flk-1 or Quek1 homologue) from cultured 10-day-old chick embryonic
      ventricular myocytes (CEVM). Reverse transcription-polymerase chain reaction
      revealed that the chick VEGF mRNAs consisted of at least four different species
      corresponding to the isoforms of 190, 166, 146 and 122 amino acids. In the
      embryonic heart and CEVM, the isoforms of 166 and 122 amino acids were dominant.
      Northern blot analysis detected an abundance of VEGF mRNA in both the embryonic
      heart and CEVM, even at the basal state. The levels of VEGF mRNA in CEVM were
      significantly augmented by forskolin (100 microM), or phorbol 12-myristate, 13
      acetate (200 nM) in a time-dependent manner in CEVM. In contrast, the basal
      levels of VEGF mRNA were attenuated by genistein (100 microM), but not by H89
      (100 microM) or bisindolylmaleimide (75 microM). Northern blot analysis also
      detected the chick flk-1 mRNA in abundance in the embryonic heart, and to a much
      lesser extent in CEVM. The expression levels of VEGF and flk-1 mRNA species were
      continuously high in the 6, 8 and 10-day-old chick embryonic hearts. In the 10
      day-old embryonic hearts, in situ hybridization confirmed that mRNA encoding VEGF
      was mainly expressed in ventricular myocytes. In contrast, the flk-1 mRNA was
      detected in the microvascular endothelial cells, and to a lesser extent in the
      ventricular myocytes. These data suggest that VEGF is produced in embryonic
      ventricular myocytes, even at the basal state, and that the levels of VEGF mRNA
      may be differently regulated by various protein kinases. VEGF produced by the
      chick embryonic heart may play important roles in embryonic cardiovascular
      development by acting on surrounding endothelial cells and, possibly, on
      ventricular myocytes themselves.

PMID- 10888257
TI  - Increased 8-hydroxyguanine formation and endonuclease activity for its repair in
      ischemic-reperfused hearts of rats.
AB  - A type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua) formation, and the
      activity for its subsequent repair, 8-OH-Gua endonuclease activity, were examined
      in an ischemia-reperfusion model of isolated rat hearts. The level of 8-OH-Gua in
      myocardial DNA was measured by a high performance liquid chromatography (HPLC)
      equipped with an electrochemical detector, and the 8-OH-Gua endonuclease activity
      was analysed by the endonuclease nicking assay using a synthetic double-stranded
      oligonucleotide containing an 8-OH-Gua residue as a substrate. The Langendorff
      perfused rat hearts were subjected to 30 or 60 min of global ischemia, followed
      by reperfusion with an oxygenated or a nitrogenated Krebs-Henseleit solution. The
      8-OH-Gua content in the DNA of the ischemic hearts reperfused with an oxygenated
      solution was three to four times higher than that of the control hearts. The
      levels of 8-OH-Gua did not increase either in the ischemic hearts reperfused with
      a nitrogenated solution or in the ischemic-reperfused hearts treated with SOD,
      mannitol or allopurinol. When the myocardial extract was incubated with the 8-OH
      Gua-containing oligonucleotide substrate, a specific cleavage at the site of an 8
      OH-Gua residue was detected. The endonuclease activity responsible for this
      cleavage increased two-fold in the ischemic-reperfused hearts, compared to the
      control. This study demonstrates that the formation of 8-OH-Gua in DNA as well as
      the level of its repair process, 8-OH-Gua endonuclease activity, increase in the
      ischemic-reperfused rat hearts in response to oxidative stress due to higher
      levels of oxygen free radicals.

PMID- 10888258
TI  - Molecular defects in sarcolemmal glycerophospholipid subclasses in diabetic
      cardiomyopathy.
AB  - Although still scarcely studied, the phospholipid component of the cell membrane
      is of absolute importance for cell function. Experimental evidence indicates that
      individual molecular species of a given phospholipid can influence specific
      membrane functions. We have examined the changes in molecular species of diacyl
      and alkenylacyl choline/ethanolamine glycerophospholipid subclasses and those of
      phosphatidylserine in purified cardiac sarcolemma of healthy and streptozotocin
      induced insulin dependent diabetic rats without or with insulin treatment. The
      relative content of plasmalogens increased in all the phospholipid classes of
      diabetic sarcolemma under study. Phosphatidylcholine and phosphatidylethanolamine
      were mostly enriched with molecular species containing linoleic acid in sn-2
      position and deprived of the molecular species containing arachidonic acid. The
      molecular species of phosphatidylserine containing either arachidonic or
      docosahexaenoic acid were less abundant in membranes from diabetic rats than in
      membranes from controls. Insulin treatment of diabetic rats restored the species
      profile of phosphatidylethanolamine and overcorrected the changes in molecular
      species of phosphatidylcholine. The results suggest that the high sarcolemmal
      level of plasmalogens and the abnormal molecular species of glycerophospholipids
      may be critical for the membrane dysfunction and defective contractility of the
      diabetic heart.

PMID- 10888259
TI  - Phentolamine prevents the adverse effects of adenosine on glycolysis and
      mechanical function in isolated working rat hearts subjected to antecedent
      ischemia.
AB  - Adenosine inhibits glycolysis from exogenous glucose, reduces proton production
      and enhances post-ischemic left ventricular minute work (LV work) following
      ischemia in isolated working rat hearts perfused with glucose and fatty acids. In
      hearts partially depleted of glycogen by antecedent ischemic stress (AIS)--two
      cycles of ischemia (10 min) and reperfusion (5 min)--adenosine stimulates rather
      than inhibits glycolysis, increases proton production and worsens recovery of
      post-ischemic LV work. We determined if the switch in adenosine effect on
      glycolysis and recovery of LV work following ischemia in hearts subject to AIS
      was due to the reduction in glycogen content per se or because of alpha
      adrenoceptor stimulation. One series of hearts underwent a 35-min period of
      substrate-free Langendorff perfusion (substrate-free glycogen depletion; SFGD)
      and a second series of hearts was subjected to AIS. Both series of hearts had a
      similar glycogen content (approximately 70 micromol/g dry wt) prior to drug
      treatment. In SFGD hearts perfused aerobically, adenosine (500 microM) inhibited
      glycolysis from exogenous glucose and reduced proton production. In SFGD hearts
      reperfused after prolonged ischemia, adenosine exerted similar effects on glucose
      metabolism and enhanced recovery of post-ischemic LV work (87.2 +/- 2.2% of
      preischemic values) relative to untreated hearts (25.9 +/- 13.3% of preischemic
      values). In AIS hearts perfused aerobically or subject to ischemia and
      reperfusion, phentolamine (1 microM) given in combination with adenosine,
      prevented adenosine-induced stimulation of glycolysis from exogenous glucose and
      reduced calculated proton production from glucose. Recoveries of post-ischemic LV
      work in AIS hearts for untreated, adenosine, phentolamine and
      adenosine/phentolamine groups were 34.4 +/- 11.4%, 8.6 +/- 3.9%, 16.3 +/- 13.5%
      and 73.2 +/- 13.1% respectively, of preischemic values. Glycogen depletion in the
      absence of ischemia does not switch the effect of adenosine from inhibition to
      stimulation of glycolysis or alter the cardioprotective properties of adenosine
      in hearts subject to ischemia and reperfusion. The detrimental switch in the
      metabolic and cardioprotective effects of adenosine, in hearts subject to AIS,
      can be prevented by phentolamine, an alpha-adrenoceptor antagonist. These data
      support the concept that modulation of glucose metabolism is an important factor
      in the mechanical functional recovery of the post-ischemic heart.

PMID- 10888260
TI  - Expression of perlecan proteoglycan in the infarct zone of mouse myocardial
      infarction.
AB  - Perlecan, a basal lamina proteoglycan, has been shown to interact with other
      extracellular matrix (ECM) components, especially type IV collagen, and is thus
      involved in ECM formation. Perlecan has also been postulated to promote growth
      factor-receptor interactions, including the binding of basic fibroblast growth
      factor (bFGF) to its receptor, and to enhance mitogenesis and angiogenesis. To
      test our hypothesis that perlecan is increased in the myocardial infarct zone, we
      examined perlecan expression after experimentally induced myocardial infarction
      in BALb/c mice by the methods of in situ hybridization, Northern blotting, and
      immunohistochemistry. In situ hybridization revealed mRNA signals for perlecan in
      the infarct marginal zone on day 2 and in the infarct interior zone around
      infarct granulation tissue on day 7. On day 14 the signals were observed at the
      center point of the infarct. The signals were detected in spindle-shaped
      mesenchymal cells (fibroblasts and myofibroblasts). Some surviving myocytes in
      the infarct marginal zone also showed positive signals. The sequential changes in
      the perlecan mRNA signal distribution paralleled those for type IV collagen mRNA.
      Northern blotting demonstrated increased expression of perlecan consistent with
      the observations of in situ hybridization. Immunopositive staining for perlecan
      was observed in the infarct zone around granulation tissue on day 7 and in the
      entire infarct zone on days 14-28. Immunostaining for bFGF was localized
      surrounding the infarct granulation tissue on day 7 and overlapped with perlecan
      immunostaining. The present results demonstrated the expression of perlecan by
      spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts) and some
      surviving myocytes in the myocardial infarct, indicating the contribution of
      perlecan to the pathological course of myocardial infarction.

PMID- 10888261
TI  - Molecular basis of electrical remodeling in atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is often
      associated with other cardiovascular disorders and diseases. AF can lead to
      thromboembolism, reduced left ventricular function and stroke, and, importantly,
      it is independently associated with increased mortality. AF is a progressive
      disease; numerous lines of evidence suggest that disease progression results from
      cumulative electrophysiological and structural remodeling of the atria. There is
      considerable interest in delineating the molecular mechanisms involved in the
      remodeling that occurs in the atria of patients with AF. Cellular
      electrophysiological studies have revealed marked reductions in the densities of
      the L-type voltage-gated Ca2+ current, I(Ca,L), the transient outward K+ current,
      I(TO), and the ultrarapid delayed rectifier K+ current, I(Kur), in atrial
      myocytes from patients in chronic AF. Similar (but not identical) changes in
      currents are evident in myocytes isolated from a canine model of AF and, in this
      case, the changes in currents are correlated with reduced expression of the
      underlying channel forming subunits. In both human and canine AF, the reduction
      in I(Ca,L) appears to be sufficient to explain the observed decreases in action
      potential duration and effective refractory period that are characteristic
      features of the remodeled atria. In addition, expression of the sarcoplasmic
      reticulum Ca2+ ATPase is reduced, suggesting that calcium cycling is affected in
      AF. These recent studies suggest that calcium overload and perturbations in
      calcium handling play prominent roles in AF-induced atrial remodeling. Although
      considerable progress has been made, further studies focused on defining the
      detailed structural, cellular and molecular changes that accompany the different
      stages of AF in humans, as well as in animal models of AF, are clearly warranted.
      It is anticipated that molecular insights gleaned from these studies will
      facilitate the development of improved therapeutic approaches to treat AF and to
      prevent the progression of the arrhythmia.

PMID- 10888262
TI  - Endothelial dysfunction limits the antihypertrophic action of bradykinin in rat
      cardiomyocytes.
AB  - We have previously demonstrated that bradykinin blocks hypertrophy of isolated
      cardiomyocytes: this is dependent on the release of nitric oxide from endothelial
      cells. In the present study, we investigated the influence of endothelial
      dysfunction on the antihypertrophic action of bradykinin. Angiotensin II (1
      microM) induced a 34 +/- 2% increase in [3H]phenylalanine incorporation
      (P<0.001), an in vitro marker of hypertrophy, in adult rat cardiomyocytes co
      cultured with bovine aortic endothelial cells. This response was blocked by
      bradykinin (10 microM), but restored by the nitric oxide synthase inhibitor.
      N(omega)-monomethyl-L-arginine (100 microM). However, the antihypertrophic effect
      of bradykinin in co-culture was abolished by 24 h pretreatment of endothelial
      cells with high glucose (25 mM, to mimic hyperglycemia) and attenuated by
      hydrogen peroxide (100 microM, to mimic oxidative stress). Pretreatment with
      oxidized low-density lipoprotein (100 microg/ml for 24 h, to mimic
      hyperlipidemia) was without effect. The hypertrophic response to angiotensin II
      was not modified by endothelial cell pretreatment. Furthermore, the ability of
      bradykinin to elevate cGMP (a marker for nitric oxide) in cardiomyocytes co
      cultured with endothelial cells was attenuated by pretreatment with either high
      glucose or hydrogen peroxide. In conclusion, loss of the cardioprotective action
      of bradykinin against angiotensin II-induced hypertrophy was associated with
      impaired nitric oxide release from dysfunctional endothelial cells.

PMID- 10888263
TI  - A farnesyltransferase inhibitor attenuates cardiac myocyte hypertrophy and gene
      expression.
AB  - The overexpression of either oncogenic ras or calmodulin in cardiac myocytes can
      elicit a hypertrophic response, albeit their recruitment by physiologically
      relevant stimuli remains unresolved. The present study utilized a pharmacological
      approach to examine the role of ras and calmodulin in norepinephrine- and
      endothelin-1-stimulated hypertrophy of neonatal rat cardiac myocytes. The
      pretreatment of cardiac myocytes with the farnesyltransferase inhibitor BMS
      191563 (25 microM) increased the level of unfarnesylated ras in the cytosolic
      fraction, and caused a concomitant 42 +/- 2% decrease in immunodetectable
      farnesylated ras in the particulate fraction. In parallel, BMS-191563
      pretreatment inhibited norepinephrine-mediated 3H-leucine uptake (80 +/- 10%
      decrease: n = 6; P<0.01), whereas a significant but less pronounced effect on the
      endothelin-1 response (46 +/- 6% decrease: n = 6; P<0.05) was observed. The
      calmodulin inhibitor W7 caused a 50 +/- 10% decrease (n = 8; P<0.05) of
      norepinephrine stimulated protein synthesis, whereas the endothelin-1 response
      was unaffected. Consistent with the recruitment of ras, BMS-191563 pretreatment
      attenuated norepinephrine and endothelin-1-stimulated extracellular signal
      regulated kinase (ERK) activity. However, PD098059-mediated inhibition of MEK
      dependent stimulation of ERK did not alter the hypertrophic response of either
      agonist. At the molecular level, the pretreatment with either BMS-191563 or W7
      attenuated the norepinephrine-mediated increase of prepro-ANP and -BNP mRNA.
      Likewise, BMS-191563 caused a significant decrease of endothelin-1-mediated
      expression of the natriuretic peptide mRNAs, but to a lesser extent, as compared
      to norepinephrine. Thus, the present study has shown the treatment of neonatal
      rat cardiac myocytes with a farnesyltransferase inhibitor can attenuate the
      hypertrophic phenotype in response to physiologically relevant stimuli, thereby
      supporting a role of the small GTP-binding protein ras. Moreover, these data
      further suggest alternative ras-independent signaling pathways are also
      implicated in the hypertrophic response, albeit, there appears to exist a
      stimulus-specific heterogeneity in their recruitment.

PMID- 10888264
TI  - Yet unrevealed aspects of histamine: questions from outside--answers at inside?

PMID- 10888265
TI  - H2-antagonists in the treatment of colon and breast cancer.
AB  - Several clinical trials have now been carried out with histamine type 2 receptor
      antagonists in cancer patients often as an adjunct to surgical resection of the
      primary tumour While promising results have been obtained in some groups of
      patients with gastrointestinal cancer, with increased survival and evidence of
      increased immunological recognition of tumour, results are less encouraging for
      breast cancer. This may be due to differences in the levels of histamine or the
      role of histamine in growth of these different tumour types.

PMID- 10888266
TI  - Histamine in brain development and tumors.
AB  - Histamine is found in developing mammalian brain in both neurons and mast cells.
      Under normal conditions, histamine H1 and H2 receptors are found in neural, glial
      and endothelial cells, and H3 receptors at least on neurons. Experimental brain
      tumors display both H1 and H2 receptors, and histamine increases permeability in
      the tumors and in the neighboring areas. Many studies have addressed
      histaminergic signalling mechanisms in cell lines originating from brain tumors.
      However, the role of histamine in normal development of brain structures,
      proliferation and differentiation of neurons and glial cells, and growth of
      malignant tumors in situ is still poorly understood.

PMID- 10888267
TI  - Histamine as an autocrine growth factor: an unusual role for a widespread
      mediator.
AB  - The involvement of histamine in cancer growth represents an old controversy and
      direct experimental evidence proving this hypothesis is not still available. In
      this paper we review the most relevant mechanisms referring to the role of
      histamine receptors, histidine decarboxylase and histamine release in the onset
      of an autocrine loop, that enables histamine to act as an autocrine growth
      factor. We postulate that this autocrine loop, that has been studied in an
      experimental mammary carcinoma model induced in rats, may be present in different
      human neoplasias. Therefore, the better understanding of this novel regulatory
      pathway that is controlled by histamine may contribute to identifying new
      therapeutic targets.

PMID- 10888268
TI  - Biosynthesis of interleukin-6, an autocrine growth factor for melanoma, is
      regulated by melanoma-derived histamine.
AB  - Interleukin-6 is an autocrine growth factor in advanced stage melanoma and
      biosynthesis of IL-6 is increased by histamine in various cell lines. In our
      study we analysed the direct relation of histamine and IL-6 synthesis in human
      melanoma cell lines. All melanoma cells contained IL-6 mRNA, but only metastatic
      melanoma cells secreted the IL-6 protein. The H1 histamine receptor antagonist
      triprolidine decreased gene expression and biosynthesis of IL-6, while other
      histamine receptor antagonists had no effect. These data indicate that endogenous
      histamine has a definite role in the regulation of local IL-6, suggesting that
      histamine and IL-6 could be part of autocrine growth regulation of the tumor.

PMID- 10888269
TI  - Adjuvant histamine in cancer immunotherapy.
AB  - Interleukin-2 (IL-2) is an effective activator of lymphocytes with anti
      neoplastic properties such as T-cells or natural killer cells, and this property
      of IL-2 has formed the basis for its widespread used as an immunotherapeutic
      agent in human neoplastic disease. In recent years, IL-2 therapy for solid
      neoplastic diseases and hematopoietic cancers has been supplemented with
      histamine dihydrochloride with the aim of counteracting immunosuppressive signals
      from monocytes/macrophages. Here we review the preclinical basis for the use of
      histamine as an adjunct to IL-2 in cancer immunotherapy.

PMID- 10888270
TI  - H1 histamine receptor antagonist inhibits constitutive growth of Jurkat T cells
      and antigen-specific proliferation of ovalbumin-specific murine T cells.
AB  - Histamine is produced from histidine by histidine decarboxylase (HDC) in many
      cells including normal and malignant lymphocytes. We examined the expression of
      HDC and the effect of histamine receptor antagonists on the proliferation of a
      human T cell line, Jurkat and on antigen-driven proliferation of lymphocytes from
      ovalbumin-immunized mice. Our results demonstrate that HDC is inducible in Jurkat
      cells by anti-CD3. The H1 receptor antagonist triprolidine dose dependently
      inhibits proliferation of both Jurkat cells and ovalbumin-stimulated murine
      lymphocytes, while the H2 antagonist ranitidine was ineffective. Alpha-fluoro
      methyl-histidine blocking HDC activity did not inhibit the T cell proliferation,
      suggesting an existing pool of histamine in T cells.

PMID- 10888271
TI  - Interaction of histamine and other bioamines with cytochromes P450: implications
      for cell growth modulation and chemopotentiation by drugs.
AB  - We have characterized microsomal and nuclear histamine sites, designated H(IC),
      through which this amine acts as an intracellular mediator of platelet
      aggregation and lymphocyte mitogenesis. A major proportion, at least, of the
      microsomal H(IC) sites are on cytochromes P450, an important family of microsomal
      enzymes that are present in all cells, but most abundant in the liver. These
      enzymes are involved in the metabolism of xenobiotics and natural substrates,
      including lipid hormones that modulate gene function and cell growth. We have
      shown that polyamines, hormones (including estrogen, testosterone and
      progesterone), antihormones (including tamoxifen and flutamide) and various
      antidepressants and antihistamines, all inhibit histamine binding to P450; we
      have postulated that, through binding to the heme moiety, intracellular histamine
      regulates cell function by modulating the catalytic activity of P450 enzymes, an
      action that may be perturbed by endogenous and exogenous substances. We now
      demonstrate that, in addition to histamine, melatonin and the biogenic amines
      dopamine, serotonin and noradrenaline bind to P450 isozymes and to cytochrome C.
      Thus, heme enzymes in general may represent common targets where multiple
      bioamines, hormones and drugs interact to influence cell function and growth.

PMID- 10888272
TI  - Involvement of polyamines in apoptosis. Facts and controversies: effectors or
      protectors?
AB  - The natural polyamines (putrescine, spermidine and spermine) are ubiquitous low
      molecular aliphatic amines that play multifunctional roles in cell growth and
      differentiation. Recently, evidence has merging that polyamines are actively
      involved in cell death. Changes in polyamine homeostasis have been reported
      during cell death of nerve cells, in programmed cell death of embryonic cells and
      in various in vitro models of apoptosis. Polyamines and many of their structural
      analogs exert cytotoxic effects in vitro as well in vivo. Furthermore, polyamine
      analogs and inhibitors of the polyamine anabolic/catabolic pathways modulate
      processes of cell death in a cell-type specific way. Much ambiguity exists in the
      working mechanisms by which polyamines mediate apoptosis since they have been
      shown to act as promoting, modulating or protective agents in apoptosis.
      Nevertheless, from the studies reviewed here it can be concluded that polyamines
      are critically involved in cellular survival which makes them suitable targets
      for therapeutic intervention that is specifically directed to cell death
      pathways.

PMID- 10888273
TI  - Long-term survival estimates of cast gold inlays and onlays with their analysis
      of failures.
AB  - The aim of the present study was to assess the clinical behaviour of cast gold
      restorations with respect to define a gold control against current and future
      ceramic and composite restorations. The study sample included 50 patients with
      303 cast gold restorations. All restorations were cemented with a non-adhesive
      technique. A total of 303 restorations were evaluated clinically and
      radiographically using modified United States Public Health Service criteria.
      Restorations recorded as having an A- or a B-rating were defined as successful.
      Of the 303 restorations, 42 were judged as failures, which resulted in a failure
      rate of 13.8% for a mean observation time (+/- s.d.) of 18.7 ( +/- 9.5) years.
      The estimated Kaplan-Meier survival rates (s.e.) were 96.1% (+/- 1.1%) at 10
      years, 87.0% (+/- 2.2%) at 20 years and 73.5% (+/- 5.4%) at 30 years. In total,
      biological reasons were counted 25 times in comparison to 17 technical reasons
      for those 42 failed cast gold restorations, with 17 secondary caries (40%) as the
      most common biological reason and with 13 retention losses (31%) as the most
      common technical reason. The endodontically treated tooth was exclusively
      identified as a risk factor. The restoration type (inlay versus onlay) did not
      influence the survival rate.

PMID- 10888274
TI  - A clinical diagnosis of diurnal (non-sleep) bruxism in denture wearers.
AB  - The purpose of this study was to establish a clinical method for diagnosing
      diurnal bruxism in denture wearers by recording masseter and anterior temporal
      electromyograph (EMG) activity. Seven suspected bruxists and five normal patients
      who wore complete dentures and/or distal extension base removable partial
      dentures were selected for participation. EMG activity in both the masseter and
      the anterior temporal muscles was recorded bilaterally during silent reading (10
      min), maximal voluntary clenching (MVC), tapping in centric occlusion, lateral
      movements, chewing and swallowing. No significant differences of EMG activity
      were found between the groups during tapping, lateral movement, chewing and
      swallowing (P> 0.05). However, during 10 min of silent reading, a significant
      difference was found between the groups when comparing masseter muscle activity
      (P < 0.05). A threshold of 10% of MVC of at least 3-s duration was used to define
      an individual bruxism event. When the muscle activity recorded during silent
      reading was further analysed using these criteria, the control group displayed no
      bruxing activity while the suspected bruxist group displayed a mean frequency of
      six bruxism events (range 2-10). It was concluded that: (a) masseter muscle
      activity recorded during 10 min of silent reading showed significant difference
      between the groups; (b) the criteria selected in this study for the detection of
      sleep bruxism can also be used to assess diurnal bruxism; and (c) it is possible
      to diagnose diurnal bruxism in denture wearers by measuring the masseter EMG
      activity during 10 min of silent reading.

PMID- 10888275
TI  - Effect of prefabricated metal post-head design on the retention of various core
      materials.
AB  - Retention of various post heads to core restorative materials is an important
      factor in the selection of prefabricated post systems and restorative materials
      for the restoration of endodontically treated teeth. This study examines the
      retention of a post-core prefabricated system in relation to core material and
      post-head design. A total of 60 samples were prepared using two different post
      systems (ParaPost Plus (PP) and ParaPost Unity (PU), with amalgam, composite or
      glass-ionomer as one of the core materials. The samples were tested using the
      Instron testing machine. The PP was superior to the PU prefabricated post with
      respect to the retention of various core materials. Retention values in
      descending order of magnitude were found to be: composite, amalgam and glass
      ionomer (significantly lower). The rhomboid serrated design of PP was superior in
      retention to the rounded smooth UP system. Composite material proved to be
      superior in retention, closely followed by amalgam, with glass-ionomer
      significantly less retentive.

PMID- 10888276
TI  - Degree of conversion in denture base materials for varied polymerization
      techniques.
AB  - New processing techniques for denture base acrylic resins have been introduced
      which have not comparatively quantified the residual monomer content. While
      proper processing keeps the residual monomer in a tolerable range for most
      patients, tissue irritation and reaction due to potentially higher residual
      monomer in these alternative techniques could be a clinical concern. Decreased
      degree of conversion may influence physical properties as well as
      biocompatibility. This investigation evaluated the residual monomer content of
      acrylic resins cured by three different polymerization modes. Materials
      (polymerization system) evaluated were: Lucitone 199 (conventional process),
      Accelar 20 (rapid boil-out), and Acron MC (microwave). Fourier transform infrared
      spectrometry (FTIR) was employed to determine the degree of conversion. All
      curing methods produced similar results (Lucitone 199 = 92.7% (0.21), Acron MC =
      92.6% (0.57), Accelar 20 = 90.9% (0-73). Conversion for Accelar 20 (rapid boil
      out technique), though statistically different (P < 0.05, ANOVA) from the other
      two materials and polymerization techniques, was only slightly less. It is
      unlikely that the rapid boil-out technique would induce more adverse tissue
      responses than the other techniques included in this study.

PMID- 10888277
TI  - Kinematic and kinetic observations on ballistic depression and elevation of the
      human mandible.
AB  - To study mandibular motions with respect to time (kinematics) and the forces
      causing and resulting from these motions (kinetics), four subjects generated
      rapid depression and elevation of the mandible (displacement of 0.224 m; peak
      velocity of 0.237 m s(-1) during depression and 0.269 m s(-1) during elevation).
      The motion of depression (duration of 0.195 s; kinetic energy of 2.072 x 10(-3)
      J) could be divided into a phase of acceleration (2.742 m s(-2); +/- 0.28 gn) and
      a phase of deceleration (2.264 m s(-2); - 0.23 gn), and the terminal excess
      kinetic energy of depression was absorbed and dissipated by, primarily, the
      temporomandibular joint. Similarly, the ensuing motion of elevation (duration of
      0.182 s; kinetic energy of 2.948 x 10(-3) J) could be divided into a phase of
      acceleration (3.498 m s(-2); + 0.36 gn) and a phase of deceleration (2.931 m s(
      2); -0.30 gn), and the terminal excess kinetic energy of elevation was absorbed
      and dissipated by, primarily, the dentitions and, secondarily, by the
      temporomandibular joint. Rapid depression of the mandible appeared to be under
      the central control of a preprogrammed motor command, and ensuing rapid elevation
      of the mandible appeared to be under the peripheral control of a segmental and/or
      transcortical reflex. During rapid depression and elevation of the mandible, the
      anterior suprahyoid, anterior temporalis, and sternocleidomastoid muscles were
      myoelectrically active 56%, 73%, and 71% of the time, respectively, and
      myomechanically active 42%, 59%, and 57% of the time, respectively. Over a follow
      up period of 12 months, the studied mandibular motions did not cause injury to
      the dentitions and temporomandibular joint.

PMID- 10888278
TI  - Effect of dental metal ions on glutathione levels in THP-1 human monocytes.
AB  - The release of metal ions from dental restorations has been well established, but
      the sublethal effects of these ions on oral tissues remain undefined. Metal ions
      are a potential cause of sublethal oxidative stress in cells. Oxidative stress is
      known to alter cellular processes which are important in the inflammation of
      tissues. The presence of oxidative stress is commonly assessed by measuring the
      oxidized (GSSG) and reduced (GSH) forms of cellular glutathione. Normally, the
      majority of cellular glutathione exists as GSH and the GSH-GSSG ratio is high.
      Since monocytes often orchestrate inflammatory responses, oxidative stress in
      monocytes is important. Our hypothesis for the current work was that metal ions
      induce oxidative stress in monocytes which is manifested by a lower GSH-GSSG
      ratio. Human THP-1 monocytes were exposed for 24 h to sublethal concentrations of
      ions of Ag, Be, Co, Cu, Hg, Ni, Pd, and Zn--all known to be released from dental
      biomaterials. GSH and GSSG were measured using colorimetric assays. Cu lowered
      the GSH-GSSG ratio as hypothesized, but the ratio could not be determined for
      other metals because other metal ions interfered with the GSSG assay. However, a
      statistically significant (ANOVA/Tukey) increase in GSH per cell was observed
      upon exposure to Ag (50%), Co (100%), Hg (250%) and Zn (10%). This increase may
      be indicative of an oxidative stress in its own right. Alterations in GSH levels
      may be important to how released metal ions alter cytokine secretion from
      monocytes and other cells which play a role in the inflammatory response to
      dental biomaterials.

PMID- 10888279
TI  - Comparative study of the temporomandibular joint space in maximum intercuspation
      and canine edge-to-edge positions in deep bite and non-deep bite subjects.
AB  - In order to study the relationship between morphological properties of the TMJ
      and the mathematically predicted force distribution in the TMJ, the geometric
      distribution of the joint space on top of the condylar surfaces was evaluated.
      Seven deep bite subjects and seven non-deep bite subjects were used, and the
      joint space in the maximum intercuspation and canine edge-to-edge positions was
      analysed in each group. Standardized images of the TMJ were taken with computed
      tomography (CT) using a mandible positioner. The comparative ratio of joint space
      (CRJS) between the maximum intercuspation and the canine edge-to-edge positions
      was calculated and summarized on the map of the mean morphological outline of the
      condyle. On the balancing-side condyle, the CRJS of small value was distributed
      mainly on the anterior edge of the condyle in the non-deep bite group, whereas,
      in the deep bite group, it was distributed on the centre of the condyle. On the
      working-side condyle, the small CRJS was distributed around the lateral pole of
      the condyle in the non-deep bite group, whereas, in the deep bite group, it was
      found around the posterior part of the condyle. The distribution pattern of CRJS
      on the upper surface of the condyle in the non-deep bite group was consistent
      with the results of previous studies on mathematical simulation of TMJ loading.
      From the results of this study, it was suggested that the distribution of
      mechanical loading on the TMJ in the eccentric mandibular position would be
      highly affected by the comparative ratio of joint space. As the comparative ratio
      of joint space would be highly affected by the condylar position, the analysis of
      the morphology of the TMJ in relation to mechanical joint loading, in a future
      investigation, should be carried out on specific mandibular positions in relation
      to the function of the TMJ to be studied.

PMID- 10888280
TI  - Viscoelastic properties of denture base resins obtained by underwater test.
AB  - The viscoelastic properties of denture base polymers, such as
      poly(methylmethacrylate) (PMMA), polycarbonate (PC), polysulfone (PSF) and
      polyethersulfone (PES) which have been used in current clinical dentistry were
      investigated. In addition, water absorption, diffusion coefficient of water into
      material, cubical expansion, specific volume and residual monomer were also
      determined. From the results of this study, the viscoelastic behaviours of the
      denture base polymers in water have been discussed. The relaxation modulus
      (Er(5)) which was calculated using a stress at 5 s from the start of measurement
      for the specimen which reached an equilibrium moisture content (wet specimen),
      decreased from 23.1 to 25.5% compared with that of PMMA stored in a desiccator
      (37 degrees C) for 1 week (dry specimen). In contrast, this decreasing ratio was
      7.0 to 10.0% for PC, PSF and PES. It is suggested that this phenomenon is caused
      by the increase of specific volume (cm3/g) with water absorption in each
      material. The water absorption of the PMMA group was relatively large in
      comparison with other material and was 1.81-1.85%. This value was within the
      range from 0.38 to 1.74% for PC, PSF and PES. The diffusion coefficients of water
      for PC, PSF and PES increased by approximately 1.5-2.7 times that of PMMA.
      Furthermore, the coefficient of cubical expansion of the wet specimen was larger
      than that of the dry specimen. The increasing ratio was 1.03-1.10 times for the
      PMMA group and 1. 18-2.38 times for PC, PSF and PES. The variation of Er(5) of
      the PMMA group with temperature in water was larger than those of PC, PSF and
      PES.

PMID- 10888281
TI  - In vitro dentin demineralization inhibition effects of an experimental
      fluoridated HEMA and water wetting agent.
AB  - The ability of fluoride-releasing resins to inhibit dentin demineralization
      remains controversial. The purpose of this study was to evaluate the caries
      inhibition of resin composite restorations with an experimental fluoridated
      hydroxyethyl methyl methacrylate (HEMA) and water wetting agent. Standardized
      Class V preparations were placed in 40 molars, the gingival margin placed below
      the cementoenamel junction. Two dentin primers (sodium fluoride, HEMA and water;
      HEMA and water) were placed in equal numbers of 20 preparations, then One-Step
      Dental Adhesive (Bisco) was applied as recommended by the manufacturer, followed
      by the placement of a resin composite restoration. Amalgam restorations with no
      primer/adhesive were placed in 10 preparations and 10 preparations were restored
      by placing One-Step Dental Adhesive, then resin composite. All teeth were
      subjected to an artificial caries challenge (pH 4.4) for 5 days. Results
      demonstrated the mean areas (microm2 +/- s.d.) of demineralization 100 microm
      from the restoration/dentin margin to be: amalgam 5,570 +/- 873; One-Step 7,038
      +/- 2,099; HEMA and water 6,126 +/- 634; fluoridated HEMA and water 3,411 +/-593.
      ANOVA and Duncan's test (P < 0.05) demonstrated the fluoridated HEMA and water
      wetting agent to have significantly less adjacent dentin demineralization than
      the other three groups. Eighty percent of HEMA and water wetting agent, 80% of
      One-Step Dental Adhesive and 100% of amalgam restorations demonstrated wall
      lesions. One hundred percent of restorations with fluoridated HEMA and water
      wetting agent demonstrated inhibition zones in adjacent dentin.

PMID- 10888282
TI  - A natural tooth's stress distribution in occlusion with a dental implant.
AB  - The loss of one or more teeth is normally treated with conventional fixed or
      removable partial dentures or with implant supported fixed or removable dentures.
      This study investigated stresses formed around the implant and the antagonist
      natural tooth under occlusal force in the substitution of a missing lower first
      molar with a rigid or resilient IMZ (Intra Mobil Zylinder) implant, using the
      finite element stress analysis method. The results indicate that a bite force of
      143 N resulted in high compressive stresses around the roots of a natural tooth
      opposing a restoration supported by an IMZ implant with rigid type abutment. It
      is speculated that these high compressive stresses may contribute to intrusion of
      the tooth.

PMID- 10888283
TI  - Dental rehabilitation using endosseous implants and orthognathic surgery in
      patients with cleft lip and palate: report of two cases.
AB  - We describe the use of endosseous implants in the autogenous particulate
      cancellous bone and marrow grafted alveoli after orthognathic surgery for dental
      rehabilitation of patients with cleft lip and palate. This procedure has been
      applied to two patients and produced good results functionally and aesthetically.
      The results are encouraging and indicate that implant placement after
      orthognathic surgery is useful for patients both with congenital missing teeth
      and retrognathic maxillae.

PMID- 10888284
TI  - Connexin mutations associated with palmoplantar keratoderma and profound deafness
      in a single family.
AB  - Recently, mutations in two gap junction genes, GJB2 and GJB3 (encoding Connexin
      26 and Connexin 31, respectively), have been shown to underlie either inherited
      hearing loss and skin disease or both disorders. In this study, we have extended
      our analysis of a small family in which palmoplantar keratoderma and various
      forms of deafness is segregating. In addition to the previously described
      sequence variant M34T in GJB2, two other sequence variants were identified: D66H
      also in GJB2 and R32W in GJB3. As D66H segregated with the skin disease, it is
      likely to underlie the palmoplantar keratoderma. The other two gap junction
      variants identified may contribute to the type of hearing impairment and the
      variable severity of the skin disease in the family.

PMID- 10888285
TI  - Nutrient intakes and characteristics of normal weight, female military personnel
      consuming foods reduced in fat or energy content.
AB  - The nutritional implications of consuming reduced fat or reduced energy foods
      (RED) were examined in 50 women who were participating in a larger study of iron
      status while enrolled in the U.S. Army Medical Department Officer Basic Course.
      The subjects recorded their food intake for a 7-day period. Reduced fat or
      reduced energy foods were identified as foods labeled "reduced-calorie, reduced
      fat, diet, or low-calorie". The women were divided into two groups, those eating
      > 14 RED per week (N = 28) and those eating < or = 14 RED (N = 22). The > 14 RED
      group tended to be Caucasian, single, had a lower body mass index (21.2 vs.
      22.5), and exercised more. The mean daily intake of the > 14 RED group was
      significantly higher in carbohydrate, dietary fiber, thiamin, riboflavin, niacin,
      vitamin B6, folacin, calcium, phosphorus, magnesium, iron, zinc, potassium, and
      sodium, and significantly lower in cholesterol. The percentage of energy from fat
      was significantly lower in the > 14 RED group than the < or = 14 RED group (p <
      0.01). There was no significant difference in energy intake between the two
      groups. More women in the > 14 RED group used dietary supplements. The > 14 group
      consumed more dairy products and less sweetened beverages. These results
      demonstrate that the consumption of reduced fat or energy foods did not have a
      significant impact on total energy intake in these normal weight women.
      Individuals consuming these foods may subsequently consume less energy from fat
      and improve the nutrient composition of their diet by selecting healthier food
      choices.

PMID- 10888286
TI  - Dietary restraint and self-reported meal sizes: diary studies with differentially
      informed consent.
AB  - Psychometric methods were used to explore the reliability and criterion validity
      of self-reported food intake in studies of dietary restraint. In Study 1 the
      reliabilities over days of daily aggregate intakes and of intakes at meals at
      particular times of day were assessed in 7 day food diaries by 27 low-BMI
      females. The sizes of particular meals correlated poorly with each other and with
      the total of all other meals; daily aggregate intakes also had poor reliability
      (Cronbach's alpha). Individuals meal sizes were consistent from day to day, with
      high inter-correlations between meal sizes, high correlations between meals at
      particular times and the sum of the remainder and high reliabilities. Aggregate
      intake had moderate criterion validity. Of individual meals, only breakfast
      achieved criterion validity, but there was a significant cubic component in its
      relationship with restraint. In Study 2, young male and female participants with
      various BMIs, completed a food diary on a single day. Again, aggregate daily
      intake had low reliability. Total intake and breakfast both had criterion
      validity, dietary restraint correlating negatively with total intake and
      breakfast size in the whole sample and in females, but there were significant
      quadratic components in the relationships. In contrast, restraint correlated
      positively with lunch size in the whole sample and in males. The combination of
      low reliability of individual meals as estimates of total intake, and the low
      criterion validity of all meals except breakfast, suggests that it may be
      inappropriate to study dietary restraint using aggregate self-reported intake
      measures.

PMID- 10888287
TI  - Sweet taste of aspartame and sucrose: effects on diet-induced thermogenesis.
AB  - Among factors that affect diet-induced thermogenesis (DIT) are the sensory
      characteristics of food. The aim of this study was to test whether the sweet
      flavour obtained with a low-energy sweetener (aspartame) or with sucrose have a
      different effect on DIT. Following a standardized breakfast, 24 healthy male
      subjects were served three test lunches in a randomized fashion. Lunch contained
      soft white cheese added with maltodextrins and aspartame, or sucrose, or
      maltodextrins only (non-sweetened control) (each 900 kcal). Energy expenditure
      (indirect calorimetry) was monitored during the five postprandial hours. For the
      first two periods of measurement (30-60 and 90-120 min after meal ingestion),
      postprandial energy expenditure was significantly increased with sucrose compared
      to maltodextrins and maltodextrins plus aspartame, whereas no significant
      difference was found between maltodextrins and maltodextrins plus aspartame. No
      significant difference between lunches was observed for DIT expressed as
      incremental area above premeal baseline energy expenditure. Plasma glucose area
      under the curve was significantly lower for sucrose compared to maltodextrins
      plus aspartame. Plasma insulin area under the curve was significantly lower for
      sucrose compared to the other tests foods. IN CONCLUSION: (1) variation in sweet
      taste induced by aspartame or by sucrose does not seem to have a major effect on
      DIT in healthy humans; (2) differences in energy expenditure observed in the
      early postprandial period suggest a substrate effect.

PMID- 10888288
TI  - Short- and long-term effects of changes in pleasantness on food intake.
AB  - This study concerns the effects of pleasantness on ad libitum food intake, liking
      and appetite over 5 successive days. Pleasantness was manipulated by varying the
      salt level in bread. Thirty-five students consumed ad libitum sandwiches for
      lunch, made with bread individually perceived as low, medium or high in
      pleasantness, in a balanced cross-over design. Pleasantness and desire-to-eat the
      sandwich were rated at first bite, after the consumption of each sandwich and at
      the end of the lunch. Fullness was rated just before and at several intervals
      after lunch. On the first day, the students ate less of the least pleasant bread
      than of the medium and most pleasant bread. On the fifth day, however,
      consumption of all breads was similar. For the least pleasant bread, energy
      intake at lunch, desire-to-eat and fullness, all increased over days, whereas
      these variables remained constant for the medium and most pleasant bread. Mean
      pleasantness ratings for all breads remained unaltered across the days. We
      conclude that, with repeated exposure, the desire-to-eat, fullness and intake of
      a less preferred food can increase over time. Thus, the relationship between
      pleasantness and food intake changes over this period.

PMID- 10888289
TI  - Antecedents and effects of consumer involvement in fish as a product group.
AB  - The importance of the symbolic value and of the product utility for a consumer's
      involvement in fish products was determined by applying a model to data collected
      in Denmark in 1999. The relative importance of these two antecedents of product
      involvement differed between two segments of consumers important to marketing
      strategies. However, the potential effects of involvement did not differ between
      the segments. Rather, the customer's involvement ensures that sign value and
      utility have effects such as greater enjoyment of shopping and higher frequency
      of usage.

PMID- 10888290
TI  - Nutrition knowledge and food intake.
AB  - In many studies, correlations between nutrition knowledge and dietary behaviour
      have failed to reach statistical significance, leading researchers to question
      the relevance of nutrition knowledge to food choice, and the value of nutrition
      education campaigns. This study aimed to investigate the relationship between
      knowledge and intake of fat, fruit and vegetables using a well-validated measure
      of nutrition knowledge. The study was a postal survey, using 1040 adult
      participants selected at random from General Practitioners' lists in England.
      Nutrition knowledge and food intake followed the expected demographic patterns.
      Knowledge was significantly associated with healthy eating, and the effect
      persisted after controlling for demographic variables. Logistic regression showed
      that respondents in the highest quintile for knowledge were almost 25 times more
      likely to meet current recommendations for fruit, vegetable and fat intake than
      those in the lowest quintile. Nutrition knowledge was shown to be a partial
      mediator of the socio-demographic variation in intake, especially for fruit and
      vegetables. This demonstrates the value of using more sophisticated statistical
      techniques to investigate associations between knowledge and food intake and
      indicates that knowledge is an important factor in explaining variations in food
      choice. The results support the likely value of including nutrition knowledge as
      a target for health education campaigns aimed at promoting healthy eating.

PMID- 10888291
TI  - The role of meat in everyday food culture: an analysis of an interview study in
      Copenhagen.
AB  - Interviews undertaken in a study of consumers' views on food quality were re
      analysed with special reference to the narrative themes raised by consumers when
      describing their views on the quality of meat and meat products. Negative
      attitudes towards meat were frequently expressed, and with more emotion than
      comments about any other food. Being based on interviews made prior to the BSE
      crisis, the study gives evidence that the popularity of meat was in a process of
      decline already before this crisis. It was found that critical attitudes centred
      around the following four themes: the manner in which meat is produced and
      processed in modern agriculture and industry, the fact that meat derives from
      animals, the food culture associated with meat eating and the perceived
      unhealthiness of meat. In spite of their critical attitudes, the interviewees
      nevertheless consumed meat on a daily basis. This study suggests that negative
      attitudes towards meat are not necessarily associated with decreased meat
      consumption, but are associated with a tendency to re-structure meals with
      special reference to the role assigned to meat.

PMID- 10888292
TI  - Differences in use and impact of computer-tailored dietary fat-feedback according
      to stage of change and education.
AB  - Computer-tailored written nutrition education has been found to be more effective
      in motivating people to reduce their consumption of fat than traditional written
      information. The present study aimed to test whether this innovative nutrition
      education intervention is also suitable for people with low motivation to change
      and low education among a self-selected sample of 699 adults. Computer-tailored
      feedback proved to be more effective in motivating precontemplators to proceed
      towards fat reduction than general information. Higher appreciation and use of
      the computer-tailored fat-feedback was found among respondents in contemplation
      than in other stages. No difference in impact of computer-tailored fat-feedback
      on fat intake was found between educational groups. Respondents with low
      education were more positive about how interesting and how personally relevant
      the tailored letters were. It was concluded that printed computer-tailored fat
      feedback can be applied successfully to motivate precontemplators and people with
      low education to (consider to) reduce their fat intake.

PMID- 10888293
TI  - Food-conditioned odour rejection in the late stages of the meal, mediating learnt
      control of meal volume by aftereffects of food consumption.
AB  - In a two-bottle choice test, rats drank more of the fluid having a novel odour
      than that having an odour which had previously been presented in the later part
      of meals on concentrated maltodextrin solution. Rats are normally more averse to
      a novel odour than to a familiar odour; therefore, the conditioned reaction to
      the odour acquired in these circumstances is likely to be an ingestive aversion,
      rather than merely a lack of preference. Furthermore, this learnt odour rejection
      was seen only in the second half of the meal, indicating that it is dependent on
      an ingestion-induced state of repletion. Together then, these observations are
      evidence that the volume of meals rich in carbohydrate can be controlled by
      learnt rejection of particular food flavours in the presence of visceral cues
      specific to repletion (previously dubbed "conditioned satiety"), the only known
      mechanism by which aftereffects of ingested energy could reduce meal volume.

PMID- 10888294
TI  - Calcium-deprived rats sham-drink CaCl2 and NaCl.
AB  - Calcium-deprived rats are often thought to increase their calcium intake as a
      result of learning, but recent studies indicate that there is also an unlearned
      component to the appetite. They also ingest large amounts of some non-calcium
      minerals, including sodium. We examined the contribution of post-ingestive
      feedback to drinking using calcium-deprived and replete rats that could sham
      drink CaCl2 and NaCl. Rats fitted with gastric cannulae in order to allow
      ingested fluids to drain freely drank 0.3 M NaCl in six 1-h sessions with their
      cannulae open (sham), followed by two sessions with their cannulae closed. Their
      intake of 0.03 M CaCl2 was then measured in a similar series of tests (six with
      cannula open followed by two with it closed). Ingestion of both NaCl and CaCl2
      was significantly greater in calcium-deprived than in replete subjects under both
      open and closed conditions. These differences reached significance within 15 min
      after the onset of drinking during the first test with NaCl, and within 5 min in
      subsequent tests. The differences in CaCl2 intake generally reached significance
      within 5 min, including during the first test. Because there was minimal
      opportunity for post-ingestive NaCl or CaCl2 to mediate learning, the results
      provide additional support that the appetite for CaCl2 and NaCl in calcium
      deprived rats can be driven solely by orosensory factors.

PMID- 10888295
TI  - Effect of quipazine, a selective 5-HT3 agonist, on dietary self-selection of
      different macronutrient diets in male and female rats.
AB  - Macronutrient intakes, 2h and 12h, following administration of a selective 5-HT3
      agonist, quipazine, N methyl, dimaleate (QUIPAZINE; 2.5, 5.0 and 7.5 mg/kg, i.p.)
      at dark onset were examined in three groups of adult male and female Wistar rats
      fed different sources of the three macronutrients: Group 1 (casein, corn starch,
      safflower oil), Group 2 (egg protein, corn starch/sucrose, lard) and Group S
      (casein hydrolysate, maltose dextrin, butter). QUIPAZINE decreased total food
      intake only in female rats from Group 1 (2 h) at a dose of 7.5 mg/kg and Group 2
      (2h and 12h) with doses of 2.5 and 7.5 mg/kg. Intakes from corn starch and corn
      starch/sucrose diet (12h) were reduced in male and female rats, respectively,
      with doses of 2.5 and 7.5 mg/kg of QUIPAZINE. In conclusion, when provided with
      different sources of the three macronutrients, quipazine injection reduces
      specifically carbohydrate ingestion from corn starch-containing diets in male and
      female rats. Thus, the nature of the macronutrient source is of major importance
      to assess the effect of a drug on nutrient-specific selection.

PMID- 10888296
TI  - Social influences on the amount of food eaten by Norway rats.
AB  - A naive observer Norway rat offered a choice between two foods, after it
      interacts with a demonstrator rat fed one of those foods, increases its
      preference for whichever food the demonstrator rat ate. It is not known whether
      interaction with a demonstrator rat would also increase the amount that an
      observer rat would eat if it were given access only to the food the demonstrator
      had eaten. In this study, each observer rat interacted with a demonstrator rat
      fed a food, either familiar or unfamiliar to the observer, and the observer was
      then offered a weighed sample of the food that the demonstrator had eaten. It was
      found that, during the first hour of testing, observer rats that had interacted
      with demonstrators fed an unfamiliar food, increased their intake of that food
      roughly four-fold. Observer rats that interacted with demonstrator rats fed a
      familiar food however, did not increase their food intake. Socially enhanced
      intake of unfamiliar food was seen only during the first hour that observers had
      access to food and was compensated for during the next 23 h of feeding. This
      short-term increase in observer intake of unfamiliar foods appeared to result
      from socially-induced motivation to ingest unfamiliar foods rather than from
      socially-induced reduction in neophobia.

PMID- 10888297
TI  - Two eating disorders: binge eating disorder and the night eating syndrome.

PMID- 10888298
TI  - Food experience and willingness to try novel foods.

PMID- 10888299
TI  - Growth factor delivery for tissue engineering.
AB  - A tissue-engineered implant is a biologic-biomaterial combination in which some
      component of tissue has been combined with a biomaterial to create a device for
      the restoration or modification of tissue or organ function. Specific growth
      factors, released from a delivery device or from co-transplanted cells, would aid
      in the induction of host parenchymal cell infiltration and improve engraftment of
      co-delivered cells for more efficient tissue regeneration or ameliorate disease
      states. The characteristic properties of growth factors are described to provide
      a biological basis for their use in tissue engineered devices. The principles of
      polymeric device development for therapeutic growth factor delivery in the
      context of tissue engineering are outlined. A review of experimental evidence
      illustrates examples of growth factor delivery from devices such as
      microparticles, scaffolds, and encapsulated cells, for their use in the
      application areas of musculoskeletal tissue, neural tissue, and hepatic tissue.

PMID- 10888300
TI  - The influence of cytotoxicity of macromolecules and of VEGF gene modulated
      vascular permeability on the enhanced permeability and retention effect in
      resistant solid tumors.
AB  - PURPOSE: To study the influence of cytotoxicity of macromolecules, VEGF gene
      expression, and vascular permeability on the enhanced permeability and retention
      (EPR) effect. METHODS: Mice bearing xenografts of A2780 multidrug resistant human
      ovarian carcinoma were treated by free doxorubicin (DOX) and N-(2
      hydroxypropyl)methacrylamide (HPMA) copolymer-bound DOX (P(GFLG)-DOX), Texas Red
      (P-TR), and FITC (P-FITC). Antitumor activity, drug distribution in tumor,
      vascular permeability, VEGF gene expression, and DNA fragmentation were studied.
      RESULTS: The accumulation of free DOX led to the VEGF gene overexpression and
      increased the vascular permeability, which in turn enhanced the drug accumulation
      in the same location. This positive feedback loop led to a highly inhomogeneous
      distribution of the drug within the tumor. In contrast, P(GFLG)-DOX down
      regulated the VEGF gene and decreased vascular permeability. This negative
      feedback seemed to prevent additional drug accumulation in dead necrotic tissue,
      resulting in a more uniform drug distribution and enhanced the antitumor activity
      P(GFLG)-DOX. CONCLUSIONS: The EPR effect significantly differed for
      macromolecules containing DOX when compared to macromolecules without drug. The
      cytotoxicity of P(GFLG)-DOX amplified the EPR effect, led to a more homogenous
      distribution of the drug, increased the average drug concentration in tumor and
      augmented its efficacy.

PMID- 10888301
TI  - Induction of apoptosis in WEHI 231 cells by cationic liposomes.
AB  - PURPOSE: Liposomes are of considerable interest as drug carriers and
      immunoadjuvants. However, few investigators have studied the changes exerted by
      liposomes in the cells with which they interact. The purpose of this study was to
      investigate whether liposomes induce apoptosis in B cells. METHODS: The mouse
      immature B cell line WEHI 231 cells and mouse splenic B cells were treated with
      liposomes, and the induction of apoptosis was evaluated by monitoring changes in
      DNA content, DNA fragmentation and chromatin condensation by flow cytometry,
      agarose gel electrophoresis and by morphological investigation. RESULTS: Cationic
      liposomes induced apoptosis in WEHI 231 cells, but neutral and anionic liposomes
      did not. A contact time of 30 min between WEHI 231 cells and cationic liposomes
      was sufficient to induce apoptosis, and 80% of the cells showed hypodiploid DNA
      content. Apoptosis induced by cationic liposomes composed of stearylamine was
      inhibited by addition of the oxidant scavenger, N-acetyl-cysteine. CONCLUSIONS:
      Cationic liposomes induced apoptosis in WEHI 231 cells, and the production of
      reactive oxygen species is important in the regulation of apoptosis induced by
      cationic liposomes. It is well known that cationic liposomes show cytotoxicity,
      and apoptosis may be one of the causes of this toxicity.

PMID- 10888302
TI  - Oxygen radical-mediated pulmonary toxicity induced by some cationic liposomes.
AB  - PURPOSE: The objectives of this study are to investigate the toxicity associated
      with polycationic liposomes and to elucidate the underlying mechanism. We tested
      the hypothesis that the positive charge of liposomes is a key determinant of
      toxicity by testing differently charged liposomes in mice. METHODS: Differently
      charged liposomal systems including cationic liposomes, LipofectAMINE and DOTAP,
      and neutral and negative liposomes were evaluated for their toxicity after
      pulmonary administration in mice. LDH assay and differential cell counts were
      performed to measure toxicity and pulmonary inflammation, respectively. Reactive
      oxygen intermediates (ROI) were assessed by chemiluminescence. RESULTS:
      Instillation of cationic liposomes elicited dose-dependent toxicity and pulmonary
      inflammation. This effect was more pronounced with the multivalent cationic
      liposome LipofectAMINE as compared to the monovalent cationic DOTAP. Neutral and
      negative liposomes did not exhibit lung toxicity. Toxicity associated with
      cationic liposomes correlated with the oxidative burst induced by the liposomes.
      LipofectAMINE induced a dose-dependent increase in ROI generation. This effect
      was less pronounced with DOTAP and absent with neutral and negative liposomes.
      CONCLUSIONS: ROI play a key role in cationic lipid-mediated toxicity. Polyvalent
      cationic liposomes cause a release of ROI which are responsible for the pulmonary
      toxicity.

PMID- 10888303
TI  - Differential recognition of ACE inhibitors in Xenopus laevis oocytes expressing
      rat PEPT1 and PEPT2.
AB  - PURPOSE: To examine the mechanism of inhibition of glycylsarcosine (GlySar)
      transport by quinapril and enalapril, and whether or not angiotensin converting
      enzyme (ACE) inhibitors are transported by PEPT2 as well as by PEPT1. METHODS:
      Xenopus laevis oocytes were cRNA-injected with rat PEPT1 or PEPT2 and the
      transport kinetics of radiolabeled GlySar were studied in the absence and
      presence of quinapril and enalapril. The two-microelectrode voltage-clamp
      technique was also performed to probe the electrogenic uptake of captopril,
      quinapril and enalapril. RESULTS: Kinetic analyses demonstrated that quinapril
      inhibited the uptake of GlySar in a noncompetitive manner in Xenopus oocytes
      injected with PEPT1 or PEPT2 (Ki = 0.8 or 0.4 mM, respectively). In contrast, a
      competitive interaction was observed between GlySar and enalapril (Ki = 10.8 mM
      for PEPT1 or 4.3 mM for PEPT2). Most significantly, captopril and enalapril, but
      not quinapril, induced inwardly-directed currents in both PEPT1- and PEPT2
      expressed oocytes. CONCLUSIONS: These results are unique in providing direct
      evidence for the substrate recognition and transport of some ACE inhibitors by
      the high- and low-affinity oligopeptide transporters. Our findings point to
      differences between PEPT1 and PEPT2 in their affinity to, rather than in their
      specificity for, ACE inhibitors.

PMID- 10888304
TI  - Role of P-glycoprotein in restricting propranolol transport in cultured rabbit
      conjunctival epithelial cell layers.
AB  - PURPOSE: To determine the role of P-glycoprotein (P-gp) in propranolol transport
      in cultured rabbit conjunctival epithelial cell layers (RCEC). METHODS: The
      localization of P-gp in the cultured RCEC as well as in the excised conjunctiva
      was determined by immunofluorescence technique. The role of P-gp in
      transepithelial transport and uptake of propranolol in conjunctival epithelial
      cells cultured on Transwell filters was evaluated in the presence and absence of
      P-gp competing substrates, an anti-P-gp monoclonal antibody (4E3 mAb), or a
      metabolic inhibitor, 2,4-dinitrophenol (2,4-DNP). RESULTS: Immunofluorescence
      studies revealed positive staining in the apical membrane of cultured RCEC and in
      the apical surface of the superficial cell layers in the excised conjunctiva, but
      not the basolateral membrane of cultured RCEC. Transport of propranolol showed
      preference in the basolateral-to-apical direction. The net secretory flux was
      saturable with a Km of 71.5 +/- 24.0 nM and a Jmax of 1.45 +/- 0.17 pmol/cm2/hr.
      Cyclosporin A, progesterone, rhodamine 123, verapamil, 4E3 mAb and 2,4-DNP all
      increased apical 50 nM propranolol uptake by 43% to 66%. On the other hand,
      neither beta-blockers (atenolol, metoprolol, and alprenolol) nor organic cation
      transporter substrates (tetraethylammonium (TEA) and guanidine), affected apical
      50 nM propranolol uptake. CONCLUSIONS: The energy-dependent efflux pump P-gp
      appears to be predominantly located on the apical plasma membrane of the
      conjunctival epithelium. It may play an important role in restricting the
      conjunctival absorption of some lipophilic drugs.

PMID- 10888305
TI  - Transepithelial transport of diphenhydramine across monolayers of the human
      intestinal epithelial cell line Caco-2.
AB  - PURPOSE: The transepithelial transport characteristics of the antihistamine,
      diphenhydramine, were studied in human intestinal Caco-2 cell monolayers to
      elucidate the mechanisms of its intestinal absorption. METHODS: The
      transepithelial transport and the cellular accumulation of diphenhydramine were
      measured using Caco-2 cell monolayers grown in Transwell chambers. RESULTS: The
      transepithelial transport of diphenhydramine from the apical to basolateral side
      was saturable, and the flux and cellular accumulation of diphenhydramine were
      dependent on the apical extracellular pH (pH 7.4 > 6.5 > 5.5). Transport and
      accumulation of diphenhydramine from the apical side were inhibited by another
      antihistamine, chlorpheniramine, while typical substrates for the renal organic
      cation transport system such as tetraethylammonium, cimetidine and guanidine had
      no effect. The transepithelial transport and cellular accumulation of
      diphenhydramine from the basolateral side were also pH-dependent and inhibited by
      chlorpheniramine. In addition, intracellular diphenhydramine preloaded was
      preferentially effluxed to the apical side, suggesting the involvement of the
      secretory pathway in diphenhydramine transport. Furthermore, diphenhydramine
      uptake from both the apical and basolateral sides was stimulated by preloading
      monolayers with chlorpheniramine (trans-stimulation effect). CONCLUSIONS:
      Transepithelial transport of diphenhydramine across Caco-2 cells is mediated by
      pH-dependent, specific transport systems that exist in both the apical and
      basolateral membranes.

PMID- 10888306
TI  - Biliary excretion of 17beta-estradiol 17beta-D-glucuronide is predominantly
      mediated by cMOAT/MRP2.
AB  - PURPOSE: The mechanism for the biliary excretion of 17beta-estradiol 17beta-D
      glucuronide (E(2)17betaG), a cholestatic metabolite of estradiol, is still
      controversial. The purpose of the present study is to examine the transport of
      E(2)17betaG across the bile canalicular membrane. METHODS: We examined the uptake
      of [3H]E(2)17betaG by isolated canalicular membrane vesicles (CMVs) prepared from
      Sprague-Dawley (SD) rats and Eisai Hyperbilirubinemic rats (EHBR) whose
      canalicular multispecific organic anion transporter/multidrug resistance
      associated protein 2 (cMOAT/MRP2) function is hereditarily defective. Also, in
      vivo biliary excretion of intravenously administered [3H]E(2)17betaG was
      examined. RESULTS: In CMVs prepared from SD rats, but not from EHBR, a marked ATP
      dependent uptake of [3H]E(2)17betaG was observed. Moreover, E(2)17betaG
      competitively inhibited the ATP-dependent uptake of [3H]2,4-dinitrophenyl-S
      glutathione (DNP-SG). In addition, no significant inhibitory effect of verapamil
      (100 microM) and PSC-833 (5 microM) on the uptake of [3H]E(2)17betaG was
      observed. In vivo, the biliary excretion of intravenously administered
      [3H]E(2)17betaG was severely impaired in EHBR while the biliary excretion of
      [3H]E(2)17betaG in SD rats was reduced by administering a cholestatic dose (10
      micromol/kg) unlabeled E(2)17betaG, but not by PSC-833 (3 mg/kg). CONCLUSIONS:
      The transport of E(2)17betaG across the bile canalicular membrane is
      predominantly mediated by cMOAT/MRP2.

PMID- 10888307
TI  - Physiological modeling of altered pharmacokinetics of a novel anticancer drug,
      UCN-01 (7-hydroxystaurosporine), caused by slow dissociation of UCN-01 from human
      alpha1-acid glycoprotein.
AB  - PURPOSE: The extremely low clearance and small distribution volume of UCN-01 in
      humans could be partly due to the high degree of binding to hAGP. The
      quantitative effects of hAGP on the pharmacokinetics of UCN-01 at several levels
      of hAGP and UCN-01 were estimated in rats given an infusion of hAGP to mimic the
      clinical situation and a physiological model for analysis was developed. METHODS:
      The plasma concentrations of UCN-01 (72.5-7250 nmol/kg i.v.) in rats given an
      infusion of hAGP, 15 or 150 nmol/h/kg, were measured by HPLC. Pharmacokinetic
      analysis under conditions assuming rapid equilibrium of protein binding and
      incorporating the dissociation rate was conducted. RESULTS: The Vdss and CLtot of
      UCN-01 (725 nmol/kg i.v.) in rats given an infusion of hAGP, 150 nmol/h/kg, fell
      to about 1/250 and 1/ 700 that in control rats. The Vdss and CLtot following 72.5
      7250 nmol/kg UCN-01 to rats given 150 nmol/h/kg hAGP were 63.9-688 ml/kg and 3.18
      32.9 ml/h/kg, respectively, indicating non-linearity due to saturation of UCN-01
      binding. The CLtot estimated by the physiological model assuming rapid
      equilibrium of UCN-01 binding to hAGP, was six times higher than the observed
      value while the CLtot estimated by the model incorporating k(off), measured using
      DCC, was comparable with the observed value. CONCLUSIONS: These results suggest
      that the slow dissociation of UCN-01 from hAGP limits its disposition and
      elimination.

PMID- 10888308
TI  - Propiverine-induced Parkinsonism: a case report and a
      pharmacokinetic/pharmacodynamic study in mice.
AB  - PURPOSE: We present a case report of propiverine-induced Parkinsonism. We
      previously reported the induction of catalepsy by amiodarone, aprindine and
      procaine, which possess a diethylaminomethyl moiety and demonstrated selective
      blockade of dopamine D2 receptors by these drugs in mice. We hypothesized that
      drugs possessing a diethylaminomethyl structure may generally induce Parkinsonism
      and/or catalepsy. METHODS: Thus, we performed a study to examine whether
      oxybutynin, pentoxyverine and etafenone, as well as propiverine, induce catalepsy
      in mice. RESULTS: The intensity of drug-induced catalepsy was in the order:
      haloperidol > etafenone > pentoxyverine > propiverine > oxybutynin. In vivo
      occupancy of dopamine D1, D2 and mACh receptors in the striatum was also
      examined. The in vitro binding affinities to the D1, D2 and mACh receptors in the
      striatum synaptic membrane were within the ranges of 2.4-140 microM, 380-4,200
      nM, and 1.2-2,800 nM, respectively. CONCLUSIONS: These results support the idea
      that any drug possessing a diethylaminomethyl moiety may contribute to the
      induction of catalepsy, possibly by occupying dopamine receptors.

PMID- 10888309
TI  - Bioequivalence study of stressed and nonstressed hard gelatin capsules using
      amoxicillin as a drug marker and gamma scintigraphy to confirm time and GI
      location of in vivo capsule rupture.
AB  - PURPOSE: Evaluate if crosslinked hard gelatin capsules (HGCs) having different in
      vitro dissolution profiles changed in vivo release times or altered
      bioavailability of a drug marker; assess if a two-tier dissolution test (with and
      without enzyme) predicted in vivo performance. METHODS: Two classifications of
      stressed HGCs were artificially produced by exposure to formaldehyde (HCHO). HGCs
      were categorized as, a) pass/pass (p/p) which met in vitro dissolution criterion
      (75% drug dissolution at 45 min), b) moderately crosslinked fail/pass (f/p) which
      failed dissolution criterion in the absence of enzymes and passed in the presence
      of enzymes, and c) severely crosslinked fail/fail (f/f) which failed in vitro
      standards with or without enzymes. A six-way, single dose bioequivalence study (n
      = 10) administered the three HGCs under the fasted and fed condition. In vivo
      capsule rupture and GI transit were monitored via gamma scintigraphy, and blood
      samples were collected through six hours. RESULTS: Each crosslinked HGC was
      bioequivalent to the control p/p capsule when using AUC(0-infinity) and Cmax for
      comparison. Mean in vivo disintegration of the p/p capsule was 7 +/- 5 min for
      the fasted condition and 11 +/- 7 min for the fed condition. In vivo rupture for
      the f/p capsule was 22 +/- 12 min and 23 +/- 11 min for the fasted and fed
      studies, respectively, while the f/f HGC ruptured at 31 +/- 15 min and 71 +/- 19
      min under the fasted and fed condition, respectively. Onset of amoxicillin
      absorption was dependent on in vivo HGC rupture and subsequent entry of the
      released radioactive marker into the small intestine. Consequently, fasted Tmax
      values were significantly later for the f/p HGC (1.62 +/- 0.53 hr) and f/f HGC
      (1.85 +/- 0.58 hr) as compared to the p/p HGC (1.17 +/- 0.30 hr). Fed Tmax values
      were statistically different only for the f/f capsule (2.55 +/- 0.44 hr) where
      Tmax values for the p/p and f/p HGCs under the fed condition were 1.50 +/- 0.47
      hr and 1.60 +/- 0.46 hr, respectively. CONCLUSIONS: A two-tier dissolution
      procedure that retested a crosslinked hard gelatin capsule with addition of
      gastric or intestinal enzymes provided an adequate in vitro indicator of the
      formulation's in vivo performance. The observed delays in the onset of
      amoxicillin absorption and Tmax for the severely crosslinked f/f HGC was
      attributed to delayed in vivo capsule rupture, however, this delay did not
      adversely change AUC(0-infinity) nor Cmax.

PMID- 10888310
TI  - Sensitivity of empirical metrics of rate of absorption in bioequivalence studies.
AB  - PURPOSE: The sensitivity and effectiveness of indirect metrics proposed for the
      assessment of comparative absorption rates in bioequivalence studies [Cmax, Tmax,
      partial AUC (AUCp), feathered slope (SLf), intercept metric (I)] were originally
      tested by assuming first-order absorption. The present study re-evaluates their
      sensitivity performances using the more realistic inverse Gaussian (IG) model
      characterizing the input process for oral drug administration. METHODS:
      Simulations were performed for both the first-order or exponential model (EX)
      which is determined by only one parameter, the mean absorption time (MAT =
      1/k(a)), and the IG model, which additionally contains a shape parameter, the
      relative dispersion of absorption time distribution (CV2A). Kinetic sensitivities
      (KS) of the indirect metrics were evaluated from bioequivalence trials (error
      free data) generated with various ratios of the true parameters (MAT and CV2A) of
      the two formulations. RESULTS: The behavior of the metrics was similar with
      respect to changes in MAT ratios with both models: KS was low with Cmax, moderate
      with SLf and AUCp, and high with I and Tmax following correction for apparent lag
      time (Tlag). Changes of the shape parameter CV2A, however, were not detectable by
      Cmax, Tmax, SLf, and AUCp. Changes in both MAT and CV2A were well reflected by I
      with CV2A - ratio > 1. I exhibited approximately full KS also with CV2A - ratio <
      1 when a correction was first applied for the apparent lag time. CONCLUSIONS: The
      time profile of absorption rates is insufficiently characterized by only one
      parameter (MAT). Indirect metrics which are sensitive enough to detect changes in
      the scale and shape of the input profile could be useful for bioequivalence
      testing. Among the tested measures, I is particularly promising when a correction
      is applied for Tlag.

PMID- 10888311
TI  - Pharmacokinetic variability and therapeutic drug monitoring actions at steady
      state.
AB  - PURPOSE: To develop a mathematical model for therapeutic drug monitoring and to
      assess the kinetic relationships between the intensity of corrective action and
      the approach of drug concentrations to target values. METHODS: A mathematical
      model that succinctly accounts for the corrective actions and the variability
      inherent in the pharmacokinetics was used. RESULTS: The validity of the
      variability term was tested using experimental data for steady state
      concentrations of the drug procainamide. The approach of the monitored process to
      the target value followed exponential kinetics and an analytical expression for
      dependence the variance with time and various dosing parameters was derived. The
      variance of the drug concentration depends critically on a single non-dimensional
      parameter containing the rate constant for the therapeutic corrective actions and
      a coefficient describing the variance rate. When the rate constant for the
      therapeutic corrective actions was less than this critical value, the variance
      increased indefinitely. CONCLUSIONS: From a dosing standpoint, large variances in
      drug concentrations are undesirable because some patients will be overdosed or
      underdosed. Since deterministic models cannot provide analytical solutions for
      the moments of drug concentration distribution functions, stochastic models can
      be used to provide useful insights into the design of therapeutic regimens.

PMID- 10888312
TI  - Pharmacologic response of a controlled-release PLGA formulation for the alpha
      melanocyte stimulating hormone analog, Melanotan-I.
AB  - PURPOSE: The objective of this study was to evaluate in vitro and in vivo the
      melanogenic activity of one-month duration Melanotan-I (MT-I) implants prepared
      using poly (D,L lactide-co-glycolide) polymer. METHODS: The biological activity
      of the samples of MT-I released in vitro from the non-irradiated or gamma
      irradiated implants was measured using a frog skin bioassay. The effect of MT-I
      on skin pigmentation was measured using a Chroma meter (reflectometer) after
      subcutaneous administration of implants containing 4 mg MT-I to guinea pigs.
      Eumelanin, the black/brown melanin pigment, was quantified in skin biopsies as
      pyrrole-2, 3, 5-tricarboxylic acid using HPLC. RESULTS: The MT-I released in
      vitro from implants after 24 hours exhibited 100% melanotropic activity in frog
      skins compared to an identical concentration of a freshly prepared MT-I standard.
      The reflectance readings demonstrated a prolonged skin darkening for up to three
      months as evidenced by the decrease in the luminance values from 0 to -4.82. A
      2.5-fold increase in eumelanin levels was observed after one month and the
      increased pigmentation lasted for 3 months. CONCLUSIONS: The melanogenic response
      to MT-I implants persisted for three months and the increase in pigmentation,
      especially the increased eumelanin levels, could provide protection from
      ultraviolet radiation.

PMID- 10888313
TI  - Subcutaneous administration of superoxide dismutase entrapped in long circulating
      liposomes: in vivo fate and therapeutic activity in an inflammation model.
AB  - PURPOSE: We are exploring liposomal delivery with the aim to change the
      pharmacokinetics and biodistribution of SOD to increase its therapeutic activity.
      From a practical point of view, a convenient route of administration would be the
      subcutaneous (s.c.) route. Liposomal size has been shown to be the most important
      factor influencing the rate and extent of drainage of liposomes from the s.c.
      injection site. METHODS: To monitor the in vivo fate of the subcutaneous
      administered SOD-containing liposomes in rats with a chronic arthritis
      inflammation, the liposomes were labeled by the co-encapsulation of the 111In
      DTPA complex in the internal water space. RESULTS: Over the initial 10h
      observation period post-injection, the small-sized poly(ethyleneglycol)-liposomes
      (mean size about 110 nm) left the site of injection to a 2-fold higher extent
      (45% of the injected dose) as compared to large-sized poly(ethyleneglycol)
      liposomes (mean size about 450 nm). Small-sized liposomes gave a 17-fold higher
      uptake in the inflamed foot than the large-sized liposomes. Comparing the
      localization in the inflamed foot with the non-inflamed foot, uptake was more
      than 15-fold higher for the small-sized liposomes as compared to the large-sized
      liposomes. After s.c. administration, small-sized SOD-liposomes showed
      substantial higher activity than large-sized SOD-liposomes. S.C. administration
      of small-sized SOD-liposomes is equally effective as i.v. administration of the
      same liposomes. I.V. administration of the large-sized SOD-liposomes yielded a
      significantly higher activity as compared to s.c. administration. CONCLUSIONS:
      These results indicate that small-sized poly(ethyleneglycol)-liposomes can be
      used for the targeting of SOD to arthritic sites after subcutaneous
      administration.

PMID- 10888314
TI  - Methotrexate esters of poly(ethylene oxide)-block-poly(2-hydroxyethyl-L
      aspartamide). Part I: Effects of the level of methotrexate conjugation on the
      stability of micelles and on drug release.
AB  - PURPOSE: To study the effects of hydrophobicity of the micelle-forming block
      copolymeric drug conjugate, methotrexate (MTX) esters of poly(ethylene oxide)
      block-poly(2-hydroxyethyl-L-aspartamide) (MTX esters of PEO-b-PHEA), on the
      stability of micelles and on drug release. METHODS: MTX esters of PEO-b-PHEA with
      three levels of MTX conjugation were synthesized. Size distribution of the
      micelles was measured by dynamic light scattering (DLS). The critical micelle
      concentration (CMC) was determined by a light scattering study. Size exclusion
      high performance liquid chromatography (SEC-HPLC) was used to study the
      equilibrium between unimers and micelles, and release of MTX at pH 7.4. RESULTS:
      MTX esters of PEO-b-PHEA with MTX substitution of 7.4%, 22%, and 54% were
      prepared. The conjugates formed micelles based on DLS. The stability of the
      micelles correlated with the level of MTX conjugation. The conjugate with 54% MTX
      had a lower CMC (0.019 mg/mL) than the conjugates with 22% MTX (0.081 mg/mL) or
      7.4% MTX (0.14 mg/mL). Micelle dissociation was significantly slower for the
      conjugate with 54% MTX than that with 22% and 7.4% MTX. Slower release of MTX
      from the micelles was also observed for the conjugate with the higher MTX
      attachment. CONCLUSIONS: MTX esters of PEO-b-PHEA can be structurally modulated
      by varying the degree of MTX substitution, which in turn changes the
      hydrophobicity of the conjugate, thereby modifying micelle stability and
      controlling drug release.

PMID- 10888315
TI  - Mechanistic studies on surfactant-induced membrane permeability enhancement.
AB  - PURPOSE: To gain some mechanistic understanding of surfactant-induced membrane
      permeabilization and identify a surfactant physical property that can be used as
      a predictor for intestinal membrane permeability enhancement. METHODS: The
      maximum surface pressures (piCMC) of series of anionic and non-ionic surfactants
      as indicators of surface activity were determined using a bubble surface
      tensiometer, and related to in vivo intestinal membrane permeability and acute
      damage data of the same surfactants from a previous work. Phospholipid bilayers
      with constant surface pressures and monolayers with different surface pressures
      were used as model membranes to systematically study membrane permeability
      enhancement and membrane penetration of surfactants at different concentrations.
      RESULTS: Surfactants that did not permeabilize or acutely damage the intestinal
      wall generally exhibited a piCMC < 25 dyne/cm. Permeability enhancement and acute
      damage increased as piCMC increased beyond 25 dyne/cm. This critical threshold
      value at around 25 dynes/cm was also observed with in vitro experiments using
      phospholipid vesicles and monolayers. Data support the hypothesis that the
      threshold phenomenon originates from the interfacial tension at the
      membrane/water interface, which controls the surface adsorption process of
      surfactant molecules onto the membrane. CONCLUSIONS: For a surfactant to
      permeabilize and acutely damage the intestinal wall, it must exhibit a surface
      pressure of greater than 25 dynes/cm. This threshold value is related to an
      intrinsic property, surface pressure, of the phospholipid membranes. Since the
      surfactant surface pressure is a property of the surfactant monomer, partition of
      the surfactant monomer, not the micelle, into the membrane is an obligate step in
      membrane permeabilization. Above the surfactant critical micelle concentration,
      CMC, micelles may act as a depot to continuously replace aqueous surfactant
      monomers taken up by the membrane. For some surfactants above CMC, sufficient
      number of monomers can partition into the membrane to cause solubilization of
      membrane lipids in surfactant micelles.

PMID- 10888316
TI  - Nuclear magnetic resonance and infrared spectroscopic analysis of nedocromil
      hydrates.
AB  - PURPOSE: Nedocromil sodium (NS), which is used in the treatment of reversible
      obstructive airway diseases, such as asthma, has been found to exist in the
      following solid phases: the heptahemihydrate, the trihydrate, a monohydrate, an
      amorphous phase, which contains variable amounts of water, and a recently
      discovered methanol + water (MW) solvate. Our aim was to apply 13C solid-state
      nuclear magnetic resonance (NMR) spectroscopy and solid-state Fourier transform
      infrared (FTIR) spectroscopy to the study of specific interactions in the various
      solid forms of NS. METHODS: The 13C solid-state NMR and FTIR spectra of the
      various solid forms of NS were obtained and were related to the crystal
      structures of NS, the conformations of the nedocromil anion, and the interactions
      of the water molecules in these crystals. RESULTS: The 13C solid-state NMR
      spectrum is sensitive to the conformation of the nedocromil anion, while the
      solid-state FTIR spectrum is sensitive to interactions of water molecules in the
      solid state. In NS monohydrate, for which the crystal structure has not yet been
      solved, and in the amorphous phase, the information about the conformations of
      the nedocromil anion and the interactions of the water molecules are deduced from
      the 13C solid-state NMR spectra and solid-state FTIR spectra, respectively.
      CONCLUSIONS: 13C solid-state NMR spectroscopy and solid-state FTIR spectroscopy
      are shown to be powerful complementary tools for probing the chemical environment
      of molecules in the solid state, specifically the conformation of the nedocromil
      anion and the interactions of water-molecules, respectively.

PMID- 10888317
TI  - Assessment of polymer-polymer interactions in blends of HPMC and film forming
      polymers by modulated temperature differential scanning calorimetry.
AB  - PURPOSE: To assess the miscibility and phase behavior of binary blends of
      hydroxypropylmethyl cellulose (HPMC) with hydroxypropyl cellulose (HPC),
      methylcellulose (MC), and polyvinylpyrrolidone (PVP). METHODS: Polymer-polymer
      miscibility was assessed by measurement of the glass transition temperature (Tg)
      and the width of the glass transition temperature (W-Tg), using modulated
      temperature differential scanning calorimetry (MTDSC). RESULTS: HPMC K4M/PVP and
      HPMC E5/MC blends were miscible as evidenced by a single, composition dependent,
      Tg throughout the entire composition range. HPMC/HPC blends were immiscible at
      all compositions. For the miscible blends, the variation in Tg with blend
      composition was compared to the values predicted by the Fox and Couchman-Karasz
      equations. At intermediate blend compositions, HPMC K4M/PVP blends exhibited
      negative deviations from ideal behavior. The Tg of the HPMC E5/MC blends was
      found to follow the Fox equation. The W-Tg measurements of the miscible blends
      gave evidence of phase separation at certain compositions. CONCLUSIONS: MTDSC was
      shown to be a useful technique in characterizing the interactions between some
      commonly used pharmaceutical polymers.

PMID- 10888318
TI  - A rapid spectrofluorimetric technique for determining drug-serum protein binding
      suitable for high-throughput screening.
AB  - PURPOSE: To develop and validate a rapid method for determining the dissociation
      constants with which pharmaceutical candidates and drugs bind to serum albumin
      and to alpha1-acid glycoprotein with the goal of deducing the extent of binding.
      METHODS: The quenching of the intrinsic tryptophan fluorescence of serum albumin
      and alpha1-acid glycoprotein was monitored by spectrofluorimetry and the data
      were used to calculate the apparent dissociation constant. Sodium warfarin was
      used to probe the warfarin-binding site of serum albumin and diazepam was used to
      probe the benzodiazepine binding site. Additionally, the binding of sodium
      salicylate, phenylbutazone, sulfinpyrazone, iophenoxic acid, theophylline,
      chloramphenicol, acetaminophen, lithium chloride and ampicillin were also
      investigated. Chlorpromazine hydrochloride and imipramine hydrochloride were used
      as probes for alpha1-acid glycoprotein. The assays were also extended to the
      multiwell format. The quenching curves were fitted to the quadratic binding
      equation to determine the dissociation constants. RESULTS: Intrinsic fluorescence
      measurements are an excellent predictor of the drug binding to human serum
      albumin and to alpha1-acid glycoprotein. These measurements detect binding to the
      warfarin and benzodiazepine binding sites of human serum albumin. The
      dissociation constants estimated using the method compare favorably to the
      dissociation constants previously reported by Epps et al. using extrinsic
      fluorescence methodology, and the results correlate well with equilibrium
      dialysis using drug displacement endpoints. CONCLUSIONS: These measurements can
      be carried out with small samples and do not require separation of the bound and
      unbound species. Additionally, the proposed methods eliminate membrane
      separations, are not compound specific and do not require analytical
      chromatography or mass spectrometry for quantitation. Spectrofluorimetry may
      prove to be a useful method for rapidly determining the protein binding of
      combinatorial libraries.

PMID- 10888319
TI  - Antifungal rapamycin analogues with reduced immunosuppressive activity.
AB  - Several 1,2,3,4-tetrahydro- and 7-N-hydroxycarbamate derivatives of the natural
      product rapamycin were prepared and assayed for their immunosuppressive and
      antifungal profiles. Substitutions at the 7-position indicate the possibility of
      a differentiated immunosuppressive to antifungal profile, whereas 40-position
      variants of the tetrahydro-analogues did not show similar differentiated
      activity.

PMID- 10888320
TI  - Syntheses and antifilarial profile of 7-chloro-4-(substituted amino) quinolines:
      a new class of antifilarial agents.
AB  - The syntheses of 7-chloro-4-(substituted amino) quinolines (2-22) and their
      antifilarial activities are delineated. Some of the screened compounds have shown
      promising filarial response and sterilization effect on female Acanthocheilonema
      viteae in rodents.

PMID- 10888321
TI  - A new synthetic approach to 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
      (Tic) derivatives via a [2 + 2 + 2] cycloaddition reaction.
AB  - Tetrahydroisoquinoline-3-carboxylic acid derivatives are prepared via a [2 + 2 +
      2] cycloaddition reaction as a key step using Wilkinson's and CpCo(CO)2
      catalysts.

PMID- 10888322
TI  - Phe and Asn side chains in DNA double strands.
AB  - The contribution of amino acid side chains to the recognition of DNA by peptides
      or proteins is evaluated by substituting single nucleobases of a DNA double
      strand by amino acid side chains. C-nucleosides with the side chains of
      phenylalanine and asparagine were synthesized and incorporated in DNA. This
      modification should allow to keep the double strand conformation. Hydrogen bonds,
      pi-pi-interactions and solvation have an influence on the double strand
      stability.

PMID- 10888323
TI  - Synthesis and biological properties of new 1beta-methylcarbapenems having
      tetrazolothioether moiety.
AB  - The synthesis and biological activities of a series of new 1beta
      methylcarbapenems 1a-l having tetrazolothioether moiety at C-5 position of
      pyrrolidine were described. Among these compounds, 1c showed the most potent
      antibacterial activity and advanced pharmacokinetics compared with imipenem and
      meropenem.

PMID- 10888324
TI  - Discovery of an orally bioavailable alkyl oxadiazole beta3 adrenergic receptor
      agonist.
AB  - 5-n-Pentyl oxadiazole substituted benzenesulfonamide 8 is a potent and selective
      beta3 adrenergic receptor agonist (beta3 EC50 = 23 nM, beta1 IC50 = 3000 nM,
      beta2 IC50 = 3000 nM). The compound has high oral bioavailability in dogs (62%)
      and rats (36%) and is among the most orally bioavailable beta3 adrenergic
      receptor agonists reported to date.

PMID- 10888325
TI  - Synthesis and SAR of benzyl and phenoxymethylene oxadiazole benzenesulfonamides
      as selective beta3 adrenergic receptor agonist antiobesity agents.
AB  - Benzyl and phenoxymethylene substituted oxadiazoles are potent and orally
      bioavailable beta3 adrenergic receptor (AR) agonists. The 4-trifluormethoxy
      substituted 5-benzyl oxadiazole 5f has an EC50 of 8 nM in the beta3 AR agonist
      assay with 100-fold selectivity over beta1 and beta2 AR binding inhibition
      activity. Its oral bioavailability in dogs is 30 +/- 4%, with a half-life of 3.8
      +/- 0.4 h. In the anesthetized rhesus, 5f evoked a dose-dependent glycerolemia
      (ED50Gly = 0.15 mg/kg). Under these conditions a heart rate increase of 15% was
      observed at a dose level of 10 mg/kg.

PMID- 10888326
TI  - Synthesis of tetrakis(multifluoro-4-pyridyl)porphin derivatives as
      acetylcholinesterase inhibitors.
AB  - New tetrakis(multifluoro-4-pyridyl)porphin derivatives (2-4) and water soluble
      porphyrin (5) were synthesized to investigate their interactions with
      acetylcholinesterase from electric eel. These compounds have been found to be the
      potent reversible inhibitors of the enzyme with Ki values of microM range. In
      addition, porphyrin (5) showed broad spectrum of anticancer activities.

PMID- 10888327
TI  - Synthesis of feruloyl-myo-inositols and their inhibitory effects on superoxide
      generation.
AB  - Ester compounds consisting of ferulic acid and myo-inositol, obtained from rice
      bran, were synthesized. The inhibitory effects of these feruloyl-myo-inositols on
      12-O-tetradecanoylphorbol-13-acetate (TPA)-induced superoxide (O2-) generation
      were examined using differentiated HL-60 cells. Among the derivatives tested,
      only 3,4,5,6-tetra-O-acetyl-1,2-di-O-[3-(4'-acetoxy-3'-methoxyphenyl)-2-pr
      openoyl]-myo-inositol (3) showed a distinct inhibitory activity.

PMID- 10888328
TI  - An enantioselective synthesis and biobehavioral evaluation of 7-fluoro-3-(p
      fluorophenyl)-2-propyltropanes.
AB  - Optically pure 7-fluorotropanes 3a-c, were synthesized as structural probes of
      the dopamine transporter. The synthesis of these compounds was accomplished
      through the asymmetric 1,3-dipolar cycloaddition reaction of the oxidopyridinium
      betaine 4 with the chiral dipolarophile (R)-p-tolyl vinyl sulfoxide. In the
      preliminary analysis, tropane 3a was found to reduce the rewarding effects of
      cocaine in the brain stimulation reward paradigm.

PMID- 10888329
TI  - Synthesis, molecular modeling and preliminary biological evaluation of 1-amino-3
      phosphono-3-cyclopentene-1-carboxylic acid and 1-amino-3-phosphono-2-cyclopentene
      1-carboxylic acid, two novel agonists of metabotropic glutamate receptors of
      group III.
AB  - On the basis of a pharmacophore definition of mGlu4 agonists, the two novel semi
      rigid derivatives 12 and 13 were designed and synthesized. The preliminary
      biological evaluation demonstrated that both compounds interact with hmGlu4a,
      while ineffective at group II receptor subtypes. In particular, derivative 13 is
      a full hmGlu4a agonist with an EC50 = 17 microM.

PMID- 10888330
TI  - Novel nikkomycin analogues: inhibitors of the fungal cell wall biosynthesis
      enzyme chitin synthase.
AB  - A series of novel nikkomycin analogue inhibitors of the chitin synthase of fungal
      cell wall was synthesized and evaluated for their inhibitory activities. Among
      them, the compound having a phenanthrene group at the terminal amino acid was
      found to possess strong anti-chitin synthase activity.

PMID- 10888331
TI  - Natural and synthetic analogues of actinomycin D as Grb2-SH2 domain blockers.
AB  - Natural analogues (D, C2, and VII) of actinomycin inhibit Grb2 SH2 domain binding
      with phosphopeptide-derived from Shc in vitro and in intracellular system. To
      study structure-activity relationships, 13 actinomycin analogues were synthesized
      and we found that the inhibition activity depended on the substituents of cyclic
      peptide groups in actinomycin and two analogues with Tyr residue are the most
      potent inhibitors with IC50 value of 0.5 and 0.8 microM, respectively.

PMID- 10888332
TI  - Synthesis and structure-activity relationships of novel fungal chitin synthase
      inhibitors.
AB  - A novel Candida albicans chitin synthase 1 (CaChs1) inhibitor, RO-41-0986 (1) was
      discovered by random screening. Systematic modification led to the identification
      of a highly potent CaChs1 inhibitor, RO-09-3024 (2), having strong antifungal
      activity against Candida spp. in vitro.

PMID- 10888333
TI  - Purpurinimides as photosensitizers: effect of the presence and position of the
      substituents in the in vivo photodynamic efficacy.
AB  - This study presents a novel approach for the regioselective synthesis of a series
      of alkyl ether analogues of purpurin-18-N-alkylimide. In the purpurinimide
      series, this is the first example which demonstrates that the presence and
      position of the substituents in the macrocycle makes a remarkable difference in
      the in vivo PDT efficacy.

PMID- 10888334
TI  - N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl)-allyl]-N-methyl
      3,5-bis-trifluoromethyl-benzamide: an orally active neurokinin NK1/NK2
      antagonist.
AB  - The stereoselective synthesis of N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan
      3-ylcarbamoyl+ ++)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide (4) and its
      NK1 and NK2 receptor binding properties are reported. In addition the potent
      inhibitory effects in vivo on sar9-SP- and beta-Ala-NKA-induced airway
      bronchoconstriction in guinea pigs are demonstrated.

PMID- 10888335
TI  - Design, synthesis, and biological evaluation of fluoronitrophenyl substituted
      folate analogues as potential inhibitors of GAR transformylase and AICAR
      transformylase.
AB  - The examination results of a novel series of potential inhibitors of glycinamide
      ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide
      transformylase (AICAR Tfase) are reported. These agents incorporate an
      electrophilic fluoronitrophenyl group that can potentially react with an active
      site nucleophile or the substrate GAR/AICAR amine via nucleophilic aromatic
      substitution.

PMID- 10888336
TI  - Design and evaluation of dihydroisoquinolines as potent and orally bioavailable
      human cytomegalovirus inhibitors.
AB  - Following the identification of first pass metabolism issues with our recently
      described anti-HCMV compounds, the naphthyridines and isoquinolines, we have
      designed a class of novel metabolically stable and orally bioavailable anti-HCMV
      agents, the dihydroisoquinolines.

PMID- 10888337
TI  - Potent new leucine aminopeptidase inhibitor of novel structure synthesised by a
      modified Wadsworth-Emmons (Horner) Wittig procedure.
AB  - The use of a leucine-derived alpha-keto-beta-aldehyde (glyoxal) as a substrate in
      the Horner-Emmons (Wadsworth) Wittig reaction has enabled the synthesis of (Z)-7
      methyl-5(S)-amino-4-oxo-methyl-oct-2-eneoate. This novel compound is a potent
      inhibitor (Ki = 76 nM) of leucine aminopeptidase and provides an interesting new
      template for the development of metallopeptidase inhibitors.

PMID- 10888338
TI  - Synthesis of new (difluoromethylphosphono)azadisaccharides designed as
      bisubstrate analogue inhibitors for GlcNAc:beta-1,4 glycosyltransferases.
AB  - We report here the design, synthesis and antifungal evaluation of a new model of
      bisubstrate analogue inhibitor for glycosyltransferases. The synthetic strategy
      relies on the reductive amination between the aldehyde derived from an N
      allylphosphono-pyrrolidine and an aminosugar.

PMID- 10888339
TI  - 1,3-Disubstituted-2-carboxy quinolones: highly potent and selective endothelin A
      receptor antagonists.
AB  - The design, synthesis, and in vitro biological activity of a series of 2-carboxy
      quinolone antagonists selective for the endothelin A receptor are presented.
      Introduction of a second acid group in position 3 of the quinolone ring increases
      dramatically the selectivity for ET(A).

PMID- 10888340
TI  - Synthesis of N-diisopropyl phosphoryl benzyltetrahydroisoquinoline, a new class
      of mitochondrial complexes I and III inhibitors.
AB  - The synthesis of N-(O,O-diisopropylphosphoryl)-benzyltetrahydroisoquinoline (3)
      has been achieved in a 'one pot' procedure from imine (2) and diisopropyl
      phosphorochloridate (1) generated in situ (POCl3 + iPrOH). Compound 3 is the
      first benzyltetrahydroisoquinoline derivative found to be a potent inhibitor of
      mitochondrial complexes I and III, and therefore it opens a new perspective with
      this series of compounds as they can be considered as new class of antitumor
      agents.

PMID- 10888341
TI  - The neural bases of strategy and skill in sentence-picture verification.
AB  - This experiment used functional Magnetic Resonance Imaging to examine the
      relation between individual differences in cognitive skill and the amount of
      cortical activation engendered by two strategies (linguistic vs. visual-spatial)
      in a sentence-picture verification task. The verbal strategy produced more
      activation in language-related cortical regions (e.g., Broca's area), whereas the
      visual-spatial strategy produced more activation in regions that have been
      implicated in visual-spatial reasoning (e.g., parietal cortex). These relations
      were also modulated by individual differences in cognitive skill: Individuals
      with better verbal skills (as measured by the reading span test) had less
      activation in Broca's area when they used the verbal strategy. Similarly,
      individuals with better visual-spatial skills (as measured by the Vandenberg,
      1971, mental rotation test) had less activation in the left parietal cortex when
      they used the visual-spatial strategy. These results indicate that language and
      visual-spatial processing are supported by partially separable networks of
      cortical regions and suggests one basis for strategy selection: the minimization
      of cognitive workload.

PMID- 10888342
TI  - Effect of ambiguity and lexical availability on syntactic and lexical production.
AB  - Speakers only sometimes include the that in sentence complement structures like
      The coach knew (that) you missed practice. Six experiments tested the predictions
      concerning optional word mention of two general approaches to language
      production. One approach claims that language production processes choose
      syntactic structures that ease the task of creating sentences, so that words are
      spoken opportunistically, as they are selected for production. The second
      approach claims that a syntactic structure is chosen that is easiest to
      comprehend, so that optional words like that are used to avoid temporarily
      ambiguous, difficult-to-comprehend sentences. In all experiments, speakers did
      not consistently include optional words to circumvent a temporary ambiguity, but
      they did omit optional words (the complementizer that) when subsequent material
      was either repeated (within a sentence) or prompted with a recall cue. The
      results suggest that speakers choose syntactic structures to permit early mention
      of available material and not to circumvent disruptive temporary ambiguities.

PMID- 10888343
TI  - Retraining therapy for chronic tinnitus. A critical analysis of its status.
AB  - Tinnitus retraining therapy (TRT), as conceived of mainly by PJ Jastreboff, has
      recently received increasing attention in the media, as well as in seminars and
      congresses on treatment methods for chronic tinnitus. It is often claimed, though
      not explicitly in scientific publications, that TRT is currently the most
      efficacious therapy for tinnitus, obtaining improvement rates exceeding 80%. This
      assertion is highly significant in light of the most likely increasing prevalence
      of chronic tinnitus and ensuing urgent demand for effective therapies. Before
      examining the evidence regarding the effectiveness of TRT, Jastreboff's
      theoretical idea of tinnitus as a neurophysiological disorder is examined and
      evaluated. This idea is plausible and is supported by some evidence. The
      interaction between neuroacoustic and emotional processes emphasized by
      Jastreboff is, however, neither new nor sufficiently elaborated with respect to
      the underlying psychological factors. The TRT intervention technique and its main
      components 'directive counselling' and use of 'noise generators' are found to be
      theoretically well grounded. The lack of detailed information concerning TRT
      implementation and the potential consequence that differing interventions may be
      labelled TRT are criticized. Jastreboff's obvious opposition to psychologists'
      participation in TRT, despite the increase in efficacy they could affect through
      utilization of cognitive restructuring techniques and behaviour modification
      interventions, is also criticized. Finally, studies regarding the efficacy of TRT
      are reviewed and severe methodological shortcomings (e.g. lack of controlled
      randomized group studies) in TRT research are noted. Taking the current state of
      evidence into account, we conclude that there is no convincing empirical support
      for the assumption that TRT is superior to other treatments, since no comparative
      studies have been conducted. It is contended that there is more substantial
      empirical support for the efficacy of cognitive-behavioural interventions in
      reducing tinnitus annoyance and tinnitus-related suffering. The necessity for
      methodologically well-designed studies to pinpoint effect sizes of TRT and
      compare them with other techniques, especially cognitive-behavioural ones, is
      emphasized.

PMID- 10888344
TI  - Reference data for DPOAE in healthy newborns.
AB  - Distortion Product Otoacoustic Emissions (DPOAE) can be used as an alternative to
      Transient Evoked Otoacoustic Emissions (TEOAE). This study aims to establish
      normal values for DPOAE in healthy newborns. DPOAE were determined with the
      Madsen Celesta 503 at 0.5, 1, 2, 4 and 8 kHz with an unequal stimulus level of
      the primaries (L1 = 65 dB SPL, L2 = 50 dB SPL). DPOAE were present in 92.4% of
      the ears of the 185 babies tested at 4 days after birth. The 5% quantile and the
      median of the DPOAE of the right and left ears were calculated for the five
      frequencies tested. At 4 kHz there was a significant sex effect (mean amplitude
      of DPOAE was higher in female than in male babies) and at 2 kHz a significant
      interaction effect was found between sex and side. The calculated reference
      limits are open to comparison with data obtained using other commercial
      equipment.

PMID- 10888345
TI  - Paediatric hearing screening in the community: a comparison of outcomes from
      transient evoked and distortion product otoacoustic emission measures.
AB  - The present study aimed to compare TEOAE screening outcomes based on different
      pass/fail criteria and the outcomes from TEOAE and DPOAE measures in children.
      For the purpose of the study, the subjects were divided into two age groups:
      group 1 (n = 36; mean age 2.7 months, SD 1.2), and group 2 (n = 29; mean age 37.5
      months, SD 16.3). Results indicated that the agreement of screening outcomes
      between pass/fail criteria for the TEOAE measure and between TEOAE and DPOAE
      measures was significantly lower for the younger group than for the older group.
      The greater variability in the younger age group could be partly attributed to
      the higher physiological noise produced by young infants. Irrespective of the
      pass/fail criteria used, the findings of the present study suggest that the OAE
      outcomes for children with weak OAEs or OAEs obscured by excessive noise were
      most variable.

PMID- 10888346
TI  - Effects of sample size on the noise floor and distortion product otoacoustic
      emissions.
AB  - This study investigated the effects of sample size on the noise floor and
      distortion product otoacoustic emissions (DPOAEs) in 55 normal-hearing subjects
      as a function of intensity. More specifically, we investigated the effects of
      sample size (12-400 sweeps) as a function of intensity (L1 = L2 = 35, 45 and 55
      dB SPL), firstly, on the identifiability of DPOAEs (2F1-F2), secondly, on the
      noise floor adjacent to DPOAEs, and thirdly, on the magnitude of DPOAEs centred
      around geometric means of 531 Hz, 1,000 Hz, 2,000 Hz and 4,000 Hz. Testing was
      conducted with a commercially available system for measuring DPOAEs (Grason
      Stadler, GSI-60). A constant F2:F1 ratio of 1.21 was used. As sample size
      increased from 12 to 400 sweeps, the noise floors decreased by about 13 dB; this
      closely corresponds to the expected 15 dB reduction based on the square root rule
      of noise reduction. The highest noise floors were measured at 531 Hz and the
      lowest noise floors at 2,000 Hz and 4,000 Hz. Identifiability increased as
      intensity increased from 35 to 55 dB SPL and as sample size increased from 12 to
      400 sweeps for all stimulus conditions. Mean DPOAEs for all frequencies (531
      4,000 Hz) appeared to decrease as sample size increased, particularly at stimulus
      levels of 35 dB and 45 dB SPL. These results may be explained by a reduction in
      the noise levels within the bandwidth of the DPOAE bin. That is, the DPOAE bin is
      comprised of the DPOAE plus background noise and these two quantities are not
      separated within the measured bin. Because the magnitude of bin containing DPOAEs
      is critically dependent on sample size, clinicians should carefully document this
      variable when collecting normative data. Similarly, clinicians who compare the
      magnitude of their DPOAEs to published data should note the sample size employed.

PMID- 10888347
TI  - Transient evoked otoacoustic emissions in 6-year-old school children: a normative
      study.
AB  - Great potential has recently been demonstrated for the application of transient
      evoked otoacoustic emissions (TEOAEs) in screening the hearing of school-aged
      children. The present study aimed to describe the range of TEOAE values obtained
      from a large cohort of 6-year-old children in school settings. Results indicated
      significant sex and ear asymmetry effects on signal-to-noise ratio, response,
      whole wave reproducibility, band reproducibility and noise levels. A prior
      history of ear infections was also shown to influence response level, whole wave
      reproducibility and band reproducibility. The sex, ear and history specific
      normative data tables derived may contribute to future improvements in the
      accuracy of hearing screening for 6-year-old school children.

PMID- 10888348
TI  - Distortion product otoacoustic emmissions in Meniere's disease.
AB  - Distortion product otoacoustic emissions (DPOAEs) are an objective, non-invasive
      measure for evaluating outer hair cell (OHC) activity. In this study DPOAEs were
      measured in 70 patients affected by Meniere's disease (MD). In addition 58 out of
      70 patients performed both an audiometric threshold evaluation pre- and
      postglycerol administration (i.e. glycerol test) and DPOAEs pre- and post-osmotic
      drug assumption. The purpose of this combined form of testing was to explore the
      effects of glycerol on the active non-linear mechanisms of the cochlea. More than
      60% of the ears with MD emitted DPOAEs despite the presence of an average hearing
      threshold level above 40 dB (HTL). Changes in the DPOAE baseline measures were
      observed in 32.4% of cases after glycerol administration. Patients were divided
      in four groups according to the different pattern of DPOAEs shown after the
      glycerol test. In particular, three-quarters of cases showed a significant
      increase in DPOAE amplitude, one-quarter of patients, who initially did not
      express DPOAEs, eventually did after intake of the osmotic agent, while no
      decreased DPOAEs were observed in these series. The different expressions of
      DPOAEs should be associated with the evolutive phases of MD. In addiction,
      elucidation of the relationship between DPOAEs and the stages of MD was an
      outcome of this test.

PMID- 10888349
TI  - Evaluation of OAE-recording as a complementary test method for adults with
      moderate to profound mental retardation.
AB  - The recording of otoacoustic emissions (OAE) was evaluated as a complementary
      test method for adults with moderate to profound mental retardation (MR). A
      portable apparatus, ILO 288 Echoport linked to a Compaq LTE 5100 notebook with
      software ILO 88 V 4.2, was used. Otoscopy and tympanometry were also performed.
      Criteria for emissions were S/N 3 dB or more and reproducibility 60% or more for
      at least three frequency-bands. The criteria for partial emissions were the same,
      but for only one or two frequencies. Two examiners were needed: one to keep the
      tested person calm and quiet and the other to handle the keyboard. Thirty-eight
      people with different degrees of MR in connection with other disabilities were
      included. They had all exhibited incomplete results in a previous hearing
      screening of more than 1,000 adults with MR. Reproducible transiently evoked OAEs
      (TEOAE) were recorded from 11 ears (7 people), partial TEOAEs from 6 ears (4
      people) and no emissions from 15 ears (10 people). Registration from 24 ears (13
      people) could not be evaluated because of too much external and internal noise.
      Eight people rejected the examination. Only four people showed emissions in both
      ears. Accordingly, 34 people (89.5%) had to be re-tested or referred for further
      investigation, 21 of them (55%) because of noisy recordings or no co-operation.
      It is concluded that the TEOAE-test in its present form cannot fulfil the demands
      for a functioning test method for this population. In single cases, however,
      TEOAE-recording can complement other audiological tests.

PMID- 10888350
TI  - Protective effect of C-reactive protein against the lethality induced by Vibrio
      vulnificus lipopolysaccharide.
AB  - Vibrio vulnificus infection has attracted special interest because of its high
      mortality. A strong clinical association exists between hepatic dysfunction and
      increased morbidity and mortality from V. vulnificus infection. In this study,
      the effect of C-reactive protein (CRP), a typical hepatogenic acute phase
      protein, on the lethality induced by V. vulnificus lipopolysaccharide (LPS) was
      investigated in galactosamine-sensitized mice. The pretreatment of CRP, in a dose
      of at least 2 mg/kg, 2 hr before the challenge of LPS completely protected mice
      against the lethality by V. vulnificus LPS. The elevation of serum tumor necrosis
      factor-alpha (TNF-alpha) induced by LPS administration was not affected by CRP
      pretreatment. However, the LPS- or TNF-alpha-induced hepatotoxicity was
      completely prevented by CRP. These results indicate that CRP does not prevent the
      synthesis, but prevents the hepatotoxic action of TNF-alpha. The possibility that
      impaired production of acute phase proteins in patients with pre-existing hepatic
      dysfunction may predispose the higher risk of V. vulnificus infection needs to be
      evaluated further.

PMID- 10888351
TI  - Cloning, sequencing and expression of the gene encoding the extracellular
      metalloprotease of Aeromonas caviae.
AB  - A gene (apk) encoding the extracellular protease of Aeromonas caviae Ae6 has been
      cloned and sequenced. For cloning the gene, the DNA genomic library was screened
      using skim milk LB agar. One clone harboring plasmid pKK3 was selected for
      sequencing. Nucleotide sequencing of the 3.5 kb region of pKK3 revealed a single
      open reading frame (ORF) of 1,785 bp encoding 595 amino acids. The deduced
      polypeptide contained a putative 16-amino acid signal peptide followed by a large
      propeptide. The N-terminal amino acid sequence of purified recombinant protein
      (APK) was consistent with the DNA sequence. This result suggested a mature
      protein of 412 amino acids with a molecular mass of 44 kDa. However, the
      molecular mass of purified recombinant APK revealed 34 kDa by SDS-PAGE,
      suggesting that further processing at the C-terminal region took place. The 2
      motifs of zinc binding sites deduced are highly conserved in the APK as well as
      in other zinc metalloproteases including Vibrio proteolyticus neutral protease,
      Emp V from Vibrio vulnificus, HA/P from Vibrio cholerae, and Pseudomonas
      aeruginosa elastase. Proteolytic activity was inhibited by EDTA, Zincov, 1,10
      phenanthroline and tetraethylenepentamine while unaffected by the other
      inhibitors tested. The protease showed maximum activity at pH 7.0 and was
      inactivated by heating at 80 C for 15 min. These results together suggest that
      APK belongs to the thermolysin family of metalloendopeptidases.

PMID- 10888352
TI  - Cell surface-associated enolase in Actinobacillus actinomycetemcomitans.
AB  - Cell surface-associated materials of Actinobacillus actinomycetemcomitans were
      extracted by a short incubation of the cell suspension in a Tris-buffered saline
      in the presence and absence of a restriction enzyme, EcoRI. The supernatants
      (which we termed EcoRI extract and surface extract, respectively) contained a
      number of extracellularly released proteins. Of these proteins, four major
      proteins were identified by N-terminal sequencing to be the 34 and 39 kDa outer
      membrane proteins, the GroEL-like protein, and a 47 kDa protein homologous to
      Haemophilus influenzae enolase. Enolase activity was found in the extracts and
      its relative amount of activity in the EcoRI extract from a culture of the mid
      exponential growth phase was estimated as 5.7% of total enzyme activity. In
      contrast, the relative amount of activity of another cytosolic enzyme, lactate
      dehydrogenase, was extremely low in the extracts and also in the culture
      supernatant. These results suggest the external localization of enolase in this
      bacterium.

PMID- 10888353
TI  - Detection of hantaviral antibodies among patients with hepatitis of unknown
      etiology in Japan.
AB  - Hantaviral antibodies were detected in the sera from patients with hepatic
      disease of unknown etiology in Japan by several different serological diagnostic
      methods. A total of 105 sera from diseased patients which were negative to A-G
      hepatitis virus infections in the Tokyo area were tested. Among them, 3 out of 73
      sera from patients with chronic hepatic disease were positive to hantaviral
      antibody by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescent
      antibody assay (IFA) and Western blot analysis (WB). Neutralizing antibody titers
      of the 3 sera to Seoul virus (SEO) were 4 to 8 times higher than those to Hantaan
      virus (HTN). However, all of the 32 sera from patients with acute hepatitis were
      negative for hantaviral antibody. Among the 60 patients with chronic hepatitis in
      Hokkaido which were serologically negative to B and C hepatitis virus infection,
      one was positive for hantaviral antibody by ELISA and WB. In contrast, the sera
      from healthy adults in Japan, 550 from the Honshu and Kyushu regions, and 1,000
      from the Hokkaido region, were negative for hantavirus antibody. These results
      show that hantaviral antibodies are more frequently detected in patients with
      hepatic disease than in healthy adults. However, the observation that no positive
      sera were detected from patients with acute hepatitis implies that hantavirus
      might not be directly related to hepatitis.

PMID- 10888354
TI  - Protective immune responses induced by a non-pathogenic simian/human
      immunodeficiency virus (SHIV) against a challenge of a pathogenic SHIV in
      monkeys.
AB  - A simian/human immunodeficiency virus (SHIV)-NM3n containing the human nef, but
      not the monkey nef, and vpr genes of SIV was inoculated into two cynomolgus
      monkeys, resulting in systemic infection with a minimum level of transient virus
      load. In order to study the nature of immune responses associated with the
      prevention of a pathogenic SHIV, the SHIV-NM3n-inoculated monkeys and three naive
      monkeys were intravenously challenged with a pathogenic SHIV containing the
      envelope gene of HIV-1 89.6. After the heterologous virus challenge, all of the
      SHIV-NM3n-inoculated animals completely avoided the loss of CD4+ T lymphocytes in
      PBMC as well as lymphoid tissues compared to pathogenic SHIV-injected control
      animals. The inhibition of CD4+ cell depletion was associated with maintaining
      the proliferative response of helper T-cells against SIV p27 in the previously
      nonpathogenic virus-inoculated animals following the pathogenic virus challenge.
      Furthermore, the decline of CD28+ cells, the increase in CD95+ cells, and the
      enhancement of in vitro apoptosis in PBMC were inhibited in the non-pathogenic
      virus-inoculated animals. These results suggest that nonpathogenic SHIV-NM3n
      infection induces the protection of monkeys from heterologous pathogenic viruses
      that may be associated with blocking the change in immune responses and the cell
      loss induced by a pathogenic virus.

PMID- 10888355
TI  - Isolation and characterization of a major antigenic component of Malassezia
      globosa to IgE antibodies in sera of patients with atopic dermatitis.
AB  - Three major components of Malassezia globosa were isolated from 2-ME extracts of
      this fungus by ion-exchange column chromatography and are referred to as Malg46a,
      Malg46b and Malg67, respectively. IgE antibodies to these components in the sera
      of patients with AD were detected by immunoblots. In Western blot, IgE antibodies
      to Malg46b were most frequently detected in the sera of AD patients. Dot blot
      with the Malg46b-containing fraction immunologically reacted with 69% of the sera
      of the patients, and with 83% of the sera of the patients who were positive for
      IgE antibodies to the 2-ME extract of M. globosa in the Western blot. The
      intensities generated for each dot correlated well with the total intensities
      generated for the 2-ME extract of M. globosa in the Western blot (r=0.763). In
      the lectin blot, Con A reacted with both Malg46a and Malg46b but not with Malg67.
      The polyclonal antibody to Malg46b reacted strongly only with the 2-ME extract of
      M. globosa and reacted slightly with M. restricta. In conclusion, a glycoprotein,
      Malg46b of M. globosa, is dominantly expressed in this fungus and is a possible
      major antigen for IgE antibodies in patients with AD.

PMID- 10888356
TI  - Protection induced in mice vaccinated with recombinant collagen-binding protein
      (CnBP) and alpha-toxoid against intramammary infection with Staphylococcus
      aureus.
AB  - Mice vaccinated with a combination of two Staphylococcus aureus antigens
      consisting of a recombinant collagen-binding protein (CnBP) and alpha-toxoid
      (alpha-toxoid) were significantly protected from intramammary challenge infection
      with S. aureus. The average number of bacteria recovered from the glands of mice
      vaccinated with the combination of CnBP/alpha-toxoid was significantly lower
      compared to the average number of bacteria recovered from the glands of mice
      vaccinated with only CnBP or alpha-toxoid or controls (P< or =0.01).
      Histopathological examination of mammary glands of mice vaccinated with CnBP
      together with alpha-toxoid showed no pathological changes, whereas glands of mice
      vaccinated with CnBP or alpha-toxoid alone developed severe mastitis and showed
      both focal and disseminated necrosis.

PMID- 10888357
TI  - Helicobacter pylori may have only a transient presence in the oral cavity and on
      the surface of oral cancer.
AB  - We used the reverse transcription polymerase chain reaction (RT-PCR) and culture
      methods to study the presence of Helicobacter pylori in the gastric and oral
      samples from a total of 116 gastritis and peptic ulcer patients, including 58
      with oral cancer. Detection rates of H. pylori were 46.6% in stomach samples and
      12.1% in oral swab samples. All of the oral cancer surface swab samples were
      positive for H. pylori, as were their gastric samples suggesting that oral H.
      pylori derived from the stomach. The culture supernatants of Streptococcus mutans
      and Prevotella intermedia inhibited the growth of the H. pylori strain and caused
      the formation of the coccal form. In cases where H. pylori was detected in the
      oral cavity samples, including the oral cancer surface samples, it was believed
      that this species had colonized the stomach and were present in the oral cavity
      only as a transient organism.

PMID- 10888358
TI  - Sequence of the gene encoding an alkaline serine proteinase of Bacillus pumilus
      TYO-67.
AB  - The complete nucleotide sequence of the gene encoding an alkaline serine
      proteinase (aprP) of Bacillus pumilus TYO-67 was determined. The sequence
      analysis showed an open reading frame of 1,149 bp (383 amino acids) that encoded
      a signal peptide consisting of 29 residues and a propeptide of 79 residues. The
      deduced 3 amino acid residues, D32, H64, and S221, were identical with 3
      essential amino acids in the catalytic center of subtilases. The sequence around
      these residues revealed that APRP was a new member of the true subtilisin
      subgroup of the subtilisin family. The highest homology was found in subtilisin
      NAT at 64.4% in the DNA sequence. The residue S189 of APRP was different from
      those of other subtilases.

PMID- 10888359
TI  - Hexagonal assembly of the magnesium salt of an R-form lipopolysaccharide from
      Klebsiella pneumoniae: its lowered stability compared with original non
      electrodialyzed preparation.
AB  - The magnesium salt of R-form lipopolysaccharide (LPS) from Klebsiella pneumoniae
      strain LEN-111 (O3-:K1-) that was prepared after the removal of cationic
      materials by electrodialysis formed essentially the same ordered hexagonal
      lattice structure with a lattice constant of 14 to 15 nm as the original non
      electrodialyzed preparation of the R-form LPS. When the magnesium salt was
      suspended in 50 mM glycine buffer or Tris buffer at pH 1.4 to 9.5 and kept at 4 C
      for 24 hr, its content of Mg was markedly decreased, and its hexagonal lattice
      structure was changed to a swollen hexagonal lattice structure with extended
      lattice constants at pH 1.4 and to a loose mesh-like structure at pH 3.0 or
      higher. In the original non-electrodialyzed preparation of the R-form LPS, the
      release of Mg and disintegration of the hexagonal lattice structure did not occur
      by suspending in buffers at pH 1.4 to 8.5 at 4 C for 24 hr, but occurred only at
      pH 9.0 or higher. The results suggest that organic cations that can be removed by
      electrodialysis play some part in tight binding to Mg2+ and in stabilizing the
      ordered hexagonal assembly of the R-form LPS.

PMID- 10888360
TI  - Effect of the sialyl Lewis X (SLe(x)) moiety on splenic accumulation of SLe(x)
      carboxymethylpullulan conjugate.
AB  - Sialyl Lewis X (SLe(x)), an E-selectin ligand, was conjugated with
      carboxymethylpullulan (CMPul) and the disposition characteristics of this
      conjugate after intravenous administration were investigated using mice with ear
      edema. The concentration of 3H-labeled SLe(x)-CMPul in the spleen was
      significantly high. When CMPul was modified with a saccharide unable to bind to E
      selectin, this splenic accumulation was not observed. The uptake of radiolabeled
      SLe(x)-CMPul by the spleen was completely inhibited by a 100-fold molar of cold
      SLe(x)-CMPul but not by a sialyl N-acetyllactosamine-CMPul conjugate (SLN-CMPul).
      Microautoradiography analyses revealed that SLe(x)-CMPul accumulated in the
      marginal zone of the spleen.

PMID- 10888361
TI  - The IgM antibody level against ganglioside GM2 correlates to the disease status
      of HIV-1-infected patients.
AB  - HIV-1 infection induces the expression of high level of GM2 ganglioside on
      infected cells and IgM antibody (Ab) against GM2 can cause complement (C)
      mediated cytolysis of HIV-1-infected cells. Since GM2 is immunogenic in human, we
      proposed that an anti-GM2 IgM Ab may be produced by some HIV-1-infected patients
      and the titer of this Ab might provide some insight into the progress of the
      disease. On this premise, the amount of IgM Ab against GM2 was determined in 124
      HIV-1-infected patients and 111 seronegative donors. As expected, the anti-GM2
      IgM Ab titers of the patients was significantly higher than that of the
      seronegative donors while the total IgM levels remained unchanged. In addition,
      we determined the CD4+ cell count and the HIV-RNA load in the HIV-1-infected
      patients. The results showed a positive correlation between the anti-GM2 IgM Ab
      titer and CD4+ cell count but a negative correlation between the anti-GM2 IgM Ab
      titer and HIV-RNA load. These suggest that anti-GM2 IgM Ab induced and/or
      enhanced by HIV-1 infection causes C-mediated cytolysis of HIV-1-infected cells
      in vivo to a certain extent, and may help lower the plateau level of the HIV-RNA
      load. Therefore, the amount of IgM Ab against GM2 may be related to the prognosis
      of HIV-1 infected patients.

PMID- 10888362
TI  - Evaluation of nine sets of PCR primers in the RNA dependent RNA polymerase region
      for detection and differentiation of members of the family Caliciviridae, Norwalk
      virus and Sapporo virus.
AB  - Norwalk virus and Sapporo virus were approved as type species of the genus
      "Norwalk-like viruses" and the genus "Sapporo-like viruses," respectively, in the
      family Caliciviridae. A total of 116 stool specimens containing Norwalk virus
      (NV) or Sapporo virus (SV) were tested by RT-PCR and Southern hybridization to
      evaluate nine sets of PCR primers and seven internal oligonucleotide probes in
      the RNA dependent RNA polymerase region of NV and SV for detection and
      differentiation of viruses in the NV and SV. Fifty-five stool samples were
      collected from 11 outbreaks of NV and/or SV gastroenteritis in an infant home,
      where residents were infants under 2 years of age, in Sapporo, Japan. Sixty
      specimens were obtained in Sapporo from sporadic cases in children, mainly under
      6 years of age, of acute gastroenteritis due to small round structured viruses
      detected by EM. There is no single primer pair to detect all NV and SV, and at
      least three primer pairs, G1 set, G2 set and Sapp35/Sapp36, are required to
      detect viruses in the NV and SV clades. Many NV and SV strains were successfully
      classified into one of the NV/genogroup I, NV/genogroup II and SV by single-round
      RT-PCR and Southern hybridization. The new detection method for SV reported in
      this study combined with those for NV previously reported may elucidate the
      importance of Norwalk virus and Sapporo virus as a cause of viral gastroenteritis
      in all age groups in the world.

PMID- 10888363
TI  - Expression of the beta-chemokines RANTES and MIP-1 beta by human brain
      microvessel endothelial cells in primary culture.
AB  - The mechanisms that regulate inflammatory cell recruitment across the blood-brain
      barrier (BBB) during CNS inflammation have not been fully characterized. Likely
      players in this process include the chemokines, small secondary messengers of
      inflammation capable of subset-specific leukocyte activation and chemoattraction.
      Primary cultures of human brain microvessel endothelial cells (HBMEC) were
      examined for their in vitro expression of the beta chemokines RANTES and MIP
      1beta. Untreated HBMEC expressed low levels of RANTES and MIP-1beta RNA that were
      significantly upregulated following cytokine treatment. Parallel studies
      performed on human umbilical vein endothelial cells (HUVEC) showed induction of
      RANTES but not MIP-1beta RNA. Following stimulation with LPS, TNF-alpha, IFN
      gamma, and IL-1beta alone or in combination, HBMEC released significant amounts
      of RANTES and MIP-1beta into the culture supernatants. RANTES secretion by HUVEC
      could be induced only with TNF-alpha/IFN-gamma. Both RANTES and MIP-1beta were
      detected by immunocytochemistry on the apical and basal surfaces of HBMEC, as
      well as bound to basal lamina-like material under the basal cell surface.
      Cytokine stimulation induced significant increase of RANTES and MIP-1beta
      molecules associated with the EC surface and subendothelial matrix. The
      expression of RANTES and MIP-1beta by HBMEC suggests that these chemokines may
      play an important role in mediating inflammatory responses and leukocyte
      trafficking across the BBB.

PMID- 10888364
TI  - New insights into the metabolic consequences of large-scale mtDNA deletions: a
      quantitative analysis of biochemical, morphological, and genetic findings in
      human skeletal muscle.
AB  - In order to study putative genotype phenotype correlations in mitochondrial
      disorders due to large-scale mtDNA deletions we performed a quantitative analysis
      of biochemical, morphological, and genetic findings in 20 patients. The size of
      the mtDNA deletions varied from 2 to 7.5 kb with a degree of heteroplasmy ranging
      from 16% to 78%. Applying improved methods for measuring respiratory chain enzyme
      activities, we found highly significant inverse correlations between the
      percentage of cytochrome c oxidase (COX)- negative fibers and citrate synthase
      (CS) normalized COX ratios. Significant correlations were also established
      between CS normalized complex I and complex IV ratios as well as between the
      degree of heteroplasmy of mtDNA deletions and the percentage of ragged red
      fibers, COX-negative fibers, and CS normalized complex I and complex IV ratios.
      Our results indicate that the degree of heteroplasmy of mtDNA deletions is
      mirrored on the histological as well as the biochemical level. Furthermore, our
      findings suggest that single large-scale deletions equally influence the
      activities of all mitochondrially encoded respiratory chain enzymes. Even low
      degrees of heteroplasmy of mtDNA deletions were found to result in biochemical
      abnormalities indicating the absence of any well-defined mtDNA deletion threshold
      in skeletal muscle.

PMID- 10888365
TI  - Involvement of apolipoprotein E in multiple sclerosis: absence of remyelination
      associated with possession of the APOE epsilon2 allele.
AB  - Lipids are a major constituent of myelin and apolipoprotein E (apoE) plays a key
      role in lipid transport. We therefore hypothesized that apoE is involved in the
      processes of demyelination and remyelination. Furthermore as there is a
      biologically significant polymorphism in the APOE gene, the APOE genotype may
      influence the course of multiple sclerosis (MS). Specifically, as there is
      reduced affinity of the apoE E2 isoform for receptors on glial cells, we
      hypothesized that remyelination is impaired in individuals with the apoE epsilon2
      allele. We determined the apoE genotypes of 71 archival cases of multiple
      sclerosis and 41 controls, reviewed the neurohistology, and performed apoE
      immunohistochemistry. ApoE immunoreactivity was increased in demyelinated areas
      compared with control white matter. ApoE immunostaining was markedly increased in
      areas of active demyelination, specifically in macrophages and astrocytes. The
      APOE allele frequencies of the cases of MS (epsilon2 = 0.06, epsilon3 = 0.8,
      epsilon4 = 0.13) resembled those of controls. Evidence of remyelination was
      identified in 25/ 71 MS cases (35%): in 25/64 patients (39%) without an epsilon2
      allele and 0/7 (0%) patients with an epsilon2 allele (p < 0.05). In conclusion,
      we provide evidence that apoE is involved in the trafficking of lipid in MS and,
      although the number of cases with this allele was small, remyelination may be
      defective in patients with the APOE epsilon2 allele.

PMID- 10888366
TI  - Role of TNF-alpha in high-dose antigen therapy in experimental autoimmune
      neuritis: inhibition of TNF-alpha by neutralizing antibodies reduces T-cell
      apoptosis and prevents liver necrosis.
AB  - TNF-alpha has been implicated as a potentially detrimental cytokine in autoimmune
      disorders of the nervous system and has been reported to be elevated in antigen
      specific therapy of experimental autoimmune neuritis (EAN) in vivo. To
      investigate the role of TNF-alpha in EAN in rats that had been subjected to
      antigen-specific therapy with human P2 protein, animals were cotreated with an
      anti-TNF-alpha neutralizing antibody and the effects of the antibody on disease
      determined. Using this strategy in adoptive transfer (AT-) EAN, antigen-induced T
      cell apoptosis in inflamed sciatic nerve and in liver was reduced to levels
      observed in control animals indicating that TNF-alpha mediates antigen-induced
      apoptosis of inflammatory T-cells. Focal liver necrosis, which had been observed
      in earlier studies after antigen therapy in AT-EAN, was prevented by passive
      immunization with neutralizing anti-TNF-alpha antibody. Unexpectedly,
      neutralization of TNF-alpha only partly abolished the protective effect of
      antigen therapy on the overall disease course. This may indicate that inhibition
      of TNF-alpha exerts beneficial effects other than through T-cell apoptosis, or
      that some of the benefit of antigen therapy is mediated by other pathways. These
      results indicate that secretion of TNF-alpha during antigen therapy has the dual
      potential to mediate beneficial apoptosis of inflammatory T-cells in the
      inflammatory lesion and to induce liver damage as a severe side effect.

PMID- 10888367
TI  - Decreased serotonergic receptor binding in rhombic lip-derived regions of the
      medulla oblongata in the sudden infant death syndrome.
AB  - The sudden infant death syndrome (SIDS) is postulated to result from a failure of
      homeostatic responses to life-threatening challenges (e.g. asphyxia, hypercapnia)
      during sleep. The ventral medulla participates in sleep-related homeostatic
      responses, including chemoreception, arousal, airway reflex control,
      thermoregulation, respiratory drive, and blood pressure regulation, in part via
      serotonin and its receptors. The ventral medulla in humans contains the arcuate
      nucleus, in which we have shown isolated defects in muscarinic and kainate
      receptor binding in SIDS victims. We also have demonstrated that the arcuate
      nucleus is anatomically linked to the nucleus raphe obscurus, a medullary region
      with serotonergic neurons. We tested the hypothesis that serotonergic receptor
      binding is decreased in both the arcuate nucleus and nucleus raphe obscurus in
      SIDS victims. Using quantitative autoradiography, 3H-lysergic acid diethylamide
      (3H-LSD binding) to serotonergic receptors (5-HT1A-D and 5-HT2 subtypes) was
      measured blinded in 19 brainstem nuclei. Cases were classified as SIDS (n = 52),
      acute controls (infants who died suddenly and in whom a complete autopsy
      established a cause of death) (n = 15), or chronic cases with oxygenation
      disorders (n = 17). Serotonergic binding was significantly lowered in the SIDS
      victims compared with controls in the arcuate nucleus (SIDS, 6 +/- 1 fmol/mg
      tissue; acutes, 19 +/- 1; and chronics, 16 +/- 1; p = 0.0001) and n. raphe
      obscurus (SIDS, 28 +/- 3 fmol/mg tissue; acutes, 66 +/- 6; and chronics, 59 +/-
      1; p = 0.0001). Binding, however, was also significantly lower (p < 0.05) in 4
      other regions that are integral parts of the medullary raphe/serotonergic system,
      and/or are derived, like the arcuate nucleus and nucleus raphe obscurus, from the
      same embryonic anlage (rhombic lip). These data suggest that a larger neuronal
      network than the arcuate nucleus alone is involved in the pathogenesis of SIDS,
      that is, a network composed of inter-related serotonergic nuclei of the ventral
      medulla that are involved in homeostatic mechanisms, and/or are derived from a
      common embryonic anlage.

PMID- 10888368
TI  - Development of connections in the human visual system during fetal mid-gestation:
      a DiI-tracing study.
AB  - Animal studies have shown that connections between the retina, lateral geniculate
      nucleus (LGN), and visual cortex begin to develop prenatally. To study the
      development of these connections in humans, regions of fixed brain from fetuses
      of 20-22 gestational weeks (GW) were injected with the fluorescent tracer DiI.
      Placement of DiI in the optic nerve or tract labeled retinogeniculate
      projections. In the LGN, these projections were already segregated into eye
      specific layers by 20 GW. Retinogeniculate segregation thus preceded cellular
      lamination of the LGN, which did not commence until 22 GW. Thalamocortical axons,
      labeled from DiI injections into the optic radiations, densely innervated the
      subplate, but did not significantly innervate the cortical plate. This pattern
      was consistent with observations of a "waiting period" in animals, when
      thalamocortical axons synapse in the subplate for days or weeks before entering
      the cortical plate. Cortical efferent neurons (labeled retrogradely from the
      optic radiations) were located in the subplate and deep layers of the cortical
      plate. In summary, human visual connections are partially formed by mid
      gestation, and undergo further refinement during and after this period. The
      program for prenatal development of visual pathways appears remarkably similar
      between humans and other primates.

PMID- 10888369
TI  - Lipoperoxidation is selectively involved in progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a neurodegenerative disorder
      characterized by extensive neurofibrillary tangle (NFT) formation and neuronal
      loss in selective neuronal populations. Currently, no clues to the biological
      events underlying the pathological process have emerged. In Alzheimer disease
      (AD), which shares with PSP the occurrence of NFTs, advanced glycation end
      products (AGEs) as well as oxidation adducts have been found to be increased in
      association with neurofibrillary pathology. The presence and the amount of lipid
      and protein oxidation markers, as well as of pyrraline and pentosidine. 2 major
      AGEs, was assessed by biochemical, immunochemical, and immunocytochemical
      analysis in midbrain tissue from 5 PSP cases, 6 sporadic AD cases, and 6 age
      matched control cases. The levels of 4-hydroxynonenal (HNE) and thiobarbituric
      acid reactive substances (TBARS), 2 major products of lipid peroxidation, were
      significantly increased by 1.6-fold (p < 0.04) and 3.9-fold (p < 0.01),
      respectively, in PSP compared with control tissues, whereas in AD only TBARS were
      significantly increased. In PSP tissue the intensity of neuronal HNE
      immunoreactivity was proportional to the extent of abnormal aggregated tau
      protein. The amount of protein oxidation products and AGEs was instead similar in
      PSP and control tissues. In AD, a higher but not significant level of pyrraline
      and pentosidine was measured, whereas the level of carbonyl groups was doubled.
      These findings indicate that in PSP, unlike in AD, lipid peroxidation is
      selectively associated with NFT formation. The intraneuronal accumulation of
      toxic aldehydes may contribute to hamper tau degradation, leading to its
      aggregation in the PSP specific abnormal filaments.

PMID- 10888371
TI  - Alpha-synuclein inclusions in Alzheimer and Lewy body diseases.
AB  - Alpha-synuclein has assumed particular neuropathological interest in the light
      both of its identification as a non-beta-amyloid plaque constituent in Alzheimer
      disease (AD), and the recent association between dominant inheritance of
      Parkinson disease (PD) and 2 missense mutations at positions 30 and 53 of the
      synuclein protein. We report a systematic study of alpha-synuclein, tau, and
      ubiquitin immunoreactivity in representative neurodegenerative disorders of late
      life. The alpha-synuclein association with Lewy bodies is variable, peripheral,
      and is not stable with respect to proteases or acid treatment, whereas there is
      no association with Pick bodies. Stable patterns of immunoreactivity included
      neurites and a novel inclusion body. Although there is an overlap between the
      presence of Lewy bodies and stable alpha-synuclein immunoreactivity, this is seen
      only in the presence of concomitant neuropathological features of AD. The novel
      alpha-synuclein inclusion body identified in pyramidal cells of the medial
      temporal lobe in particular was found in AD and in the Lewy body variant of AD,
      and was associated neither with ubiquitin nor tau protein. The inclusion is
      therefore neither a Lewy body nor a PHF-core body, but may be confused with the
      Lewy body, particularly in the Lewy body variant of AD. Abnormal processing of
      alpha-synuclein leading to its deposition in the form of proteolytically stable
      deposits is a particular feature of the intermediate stages of AD.

PMID- 10888370
TI  - Ultrastructural analysis and TUNEL demonstrate motor neuron apoptosis in Werdnig
      Hoffmann disease.
AB  - Werdnig-Hoffmann disease (WHD) is the most severe clinical type of spinal
      muscular atrophy characterized by loss of lower motor neurons and paralysis. We
      examined the hypothesis that disease pathogenesis is based on an inappropriate
      persistence of normally occurring motor neuron programmed cell death. The
      diagnosis of WHD was made on the basis of clinical findings,
      electromyoneurography, and biopsy, and further confirmed by mutation analysis of
      the survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP)
      genes using PCR. We used ultrastructural analysis as well as TUNEL and ISEL
      methods to assess DNA fragmentation, and immunocytochemistry to identify
      expression of the apoptosis-related proteins bcl-2 and p53. A significant number
      of motor neurons in the spinal cord of children with WHD were shown to die by
      apoptosis. As revealed by TUNEL, dying neurons in WHD patients comprised 0.2%
      6.4% of the neuron numbers counted. This finding contradicts earlier studies that
      failed to find such evidence and suggests that early blockade of prolonged motor
      neuron apoptosis may be a potential therapeutic strategy for WHD.

PMID- 10888372
TI  - Report of the Joint Working Group on Image-guided Diagnosis and Treatment. April
      12-14, 1999. Washington, D.C.

PMID- 10888373
TI  - Biochemical diagnosis of aortic dissection: from bench to bedside.
AB  - Aortic dissection is an acute cardiovascular disease associated with high
      mortality and morbidity. Although uncommon, recent studies have shown that the
      incidence of this catastrophic disease is steadily increasing. Unfortunately, the
      disease is still not well recognized on clinical presentation due to lack of
      specific signs and symptoms. As early diagnosis and initial management are
      critical for survival, we focused on developing a biochemical diagnostic approach
      for this disease given its meritorious properties in use in the acute clinical
      situation and additional projected combined use with established imaging
      modalities. Studies using an assay developed against smooth muscle myosin heavy
      chain, a protein which is released from the aortic medial smooth muscle cells on
      insult to the aortic wall, showed promising results for use of this assay in the
      diagnosis of aortic dissection. The background of this pioneering assay in
      addition to its clinical use are discussed in this review.

PMID- 10888374
TI  - Early alteration of coronary hemodynamics in late restenosis after coronary
      angioplasty.
AB  - It is not known whether changes in coronary hemodynamics may antedate the
      development of restenosis after percutaneous coronary transluminal angioplasty
      (PTCA). The purpose of this study was to evaluate the early change in coronary
      microvascular function in patients with late restenosis after PTCA. Coronary
      hemodynamics were studied in series before, immediately after, 2 weeks and 3
      months after successful PTCA in 12 male patients with a single lesion of the left
      anterior descending coronary artery. In each patient, great cardiac venous flow
      (GCVF) and oxygen content were measured both at baseline and during hyperemia
      induced by adenosine infusion. The sequential changes of coronary hemodynamics
      were compared between patients with and without restenosis at 3 months after
      PTCA. Basic characteristics did not differ between the patients with (n = 6) and
      those without restenosis (n = 6). Luminal diameter stenosis (in percentage) was
      also similar between the two groups both before (79.2 +/- 18.4% vs 83.0 +/- 9.6%,
      p = NS) and up to 2 weeks after PTCA (25.8 +/- 10.9% vs 28.5 +/- 7.9%, p = NS).
      In patients without restenosis, basal and hyperemic GCVF was unchanged up to 2
      weeks after PTCA. There was a significant increase in CFR 3 months after PTCA. In
      patients with restenosis, basal GCVF was significantly increased and hyperemic
      GCVF was unchanged immediately after PTCA. However, 2 weeks after PTCA, basal
      GCVF was decreased while luminal diameter was still preserved. In comparison with
      those without restenosis, patients with restenosis had significantly lower CFR
      before (1.98 +/- 0.42 vs 2.69 +/- 0.46, p = 0.019), immediately after (1.47 +/-
      0.27 vs 2.24 +/- 0.47, p = 0.006) and 3 months after PTCA (1.51 +/- 0.32 vs 3.40
      +/- 0.54, p = 0.001). In patients without restenosis, the recovery of coronary
      microvascular function was delayed up to 3 months after PTCA. In patients with
      late restenosis, basal coronary microvascular tone was altered within 2 weeks
      after PTCA suggesting early deterioration of coronary microvascular function
      before the development of angiographic restenosis.

PMID- 10888375
TI  - Increased hyperkinesis in noninfarcted areas during short-term follow-up in
      patients with first anterior acute myocardial infarction treated by direct
      percutaneous transluminal coronary angioplasty.
AB  - The time course and clinical significance of hyperkinetic wall motion (HWM) in a
      noninfarcted area in direct percutaneous transluminal coronary angioplasty (PTCA)
      has not been clearly demonstrated in patients with acute myocardial infarction
      (AMI). The objectives of this study were to examine the change in HWM during one
      month follow-up after direct PTCA and determine its impact on the recovery of
      global left ventricular function. A total of 61 patients with first anteroseptal
      AMI and one vessel disease were evaluated. The paired left ventriculograms in the
      30 degrees right anterior oblique view taken both at baseline and follow-up were
      analyzed by the centerline and area length methods. The severity of hypokinesis
      was expressed by mean regional wall motion (standard deviation/chord) in most
      hypocontractile 50% of chords respondable to left anterior descending coronary
      artery area and HWM by mean regional wall motion in most hypercontractile 50% of
      chords of noninfarcted area. HWM increased from 0.18 +/- 1.07 to 0.48 +/- 1.30 (p
      = 0.0608). The delta global ejection fraction (global ejection fraction at follow
      up minus global ejection fraction at baseline) was correlated with both delta
      infarcted wall motion (infarcted wall motion at follow-up minus infarcted wall
      motion at baseline) and delta HWM (HWM at follow-up minus HWM at baseline) (r =
      0.576, p < 0.0001, r= 0.383, p = 0.0036, respectively) during follow-up. Further,
      the delta global ejection fraction showed better correlation with delta (HWM +
      infarcted wall motion) [(HWM plus infarcted wall motion at follow-up) minus (HWM
      plus infarcted wall motion at baseline)] (r= 0.593, p < 0.0001). Direct PTCA
      resulted in the enhancement of HWVM, which contributed to the increase in the
      global ejection fraction with the recovery of infarcted wall motion.

PMID- 10888376
TI  - A simple technique for anatomical slow pathway ablation in atrioventricular nodal
      reentrant tachycardia.
AB  - The slow pathway potential or the slow potential serves as a useful marker in
      catheter ablation of the slow pathway. However, an anatomical approach without
      recording of these potentials is also an effective way to cure atrioventricular
      nodal reentrant tachycardia (AVNRT). Moreover, the origin of these potentials is
      a matter of controversy. We compared 2 approaches to ascertain whether or not
      recording of these potentials is necessary in eliminating the slow pathway and to
      estimate the usefulness of the simple anatomical approach. The study population
      consisted of 24 patients with a conventional approach (Group P) and 19 patients
      with an anatomical approach (Group A). In group A, the ablation site was
      determined by fluoroscopy, which was the lowest one-third of the area between the
      His bundle electrogram recorded position and the coronary sinus orifice at the
      right anterior oblique view, and just in front of and above the coronary sinus
      orifice also posterior to the His catheter at the left anterior oblique view
      where the His catheter was seen tangentially. The slow pathway was successfully
      ablated in all patients without any complications, including more than first
      degree AV block. Although there were no significant differences in total energy
      or number of applications between the 2 groups, the procedure time was
      significantly shorter in group A (p < 0.01). In conclusion, recording of the slow
      pathway potential or the slow potential is not always necessary for slow pathway
      ablation in the treatment of AVNRT. Because our anatomical approach was performed
      simply, effectively and safely, it is recommended for the slow pathway ablation
      of AVNRT.

PMID- 10888377
TI  - Coronary flow reserve and ischemic-like electrocardiogram in patients with
      symptomatic mitral valve prolapse.
AB  - The purpose of the present study was to determine whether coronary microvascular
      function is impaired in patients with symptomatic mitral valve prolapse (MVP) and
      whether ischemia-like ECG, if present, is related to coronary microvascular
      dysfunction. Twenty chest pain patients with normal coronary angiograms and MVP
      proven by echocardiogram were included. Both treadmill exercise test (TET) and
      coronary hemodynamic study were done in each patient. Coronary flow reserve (CFR)
      was determined by measuring coronary sinus flow (CSF) or great cardiac venous
      flow (GCVF) both at baseline and after dipyridamole 0.56 mg/kg IV for 4 minutes
      (maximum). All patients were divided into 2 groups with either negative (TET-) or
      positive results of TET (TET+). Another 10 subjects with atypical chest pain,
      normal coronary angiograms, echocardiogram and TET were used as controls. There
      were no differences in GCVF, either at baseline or after dipyridamole infusion,
      among the 3 groups. Calculated CFR using GCVF was similar among the 3 groups.
      However, baseline CSF was higher in the TET+ group (TET- vs TET+ vs control: 77
      +/- 24 vs 96 +/- 31 vs 75 +/- 12 ml/min, p < 0.05) and maximum CSF was lower in
      the TET- group (TET- vs TET+ vs control: 167 +/- 25 vs 219 +/- 85 vs 238 +/- 80
      ml/min, p < 0.05). Calculated CFR using CSF was significantly reduced in both the
      TET- (2.26 +/- 0.4) and TET+ groups (2.31 +/- 0.7) as compared with the control
      subjects (3.18 +/- 0.95, p < 0.01). There were no differences in any of the
      hemodynamic parameters between the TET- and TET+ groups. Coronary microvascular
      function could be impaired in patients with symptomatic MVP. Such impairment,
      when presented, was probably regional and outside the territory of the left
      anterior descending coronary artery. However, it was irrelevant to the presence
      of ischemic-like ECG during exercise.

PMID- 10888378
TI  - Clinical analysis of hypertrophic cardiomyopathy which evolved into dilated phase
      during long-term follow-up.
AB  - The aim of the present study was to analyze the incidence, clinical features and
      prognosis of patients with hypertrophic cardiomyopathy (HCM) which evolved into
      dilated phase HCM. The medical records of 43 patients with HCM followed up for at
      least 10 years were analyzed retrospectively. The patients were divided into two
      groups: group A consisting of patients with dilated-phase HCM defined by a left
      ventricular end diastolic dimension (LVDD) of 55 mm or more and a left
      ventricular ejection fraction (LVEF) of less than 50% obtained by
      echocardiography, and group B, consisting of patients with HCM that did not
      evolve into dilated phase HCM. During the mean follow-up of 16.7 years, 10
      patients (23.3%) evolved into dilated phase HCM (group A) while the remaining 33
      patients (76.7%) did not (group B). Ventricular tachycardia (VT) occurred in 7 of
      the 10 patients (70.0%) in group A and in 5 of the 33 patients (15.2%) in group B
      (p < 0.001). An increase in LVDD and decreases in LVEF and SV1 + RV5 in the
      electrocardiogram were observed during the early phase of the follow-up period in
      group A, while these changes were gradual in group B. Cardiac death occurred in 5
      (50.0%) of the 10 patients in group A and in 2 (6.1%) of the 33 patients in group
      B (p < 0.001). In conclusion, dilated-phase HCM is characterized by decreases in
      LVEF and SV + RV5 and an increase in LVDD during the early phase of follow-up
      period, and is associated with an increased incidence of VT and a poor prognosis.

PMID- 10888379
TI  - Angiotensin-converting enzyme gene polymorphism and geometric patterns of
      hypertensive left ventricular hypertrophy.
AB  - Polymorphism in the angiotensin-converting enzyme (ACE) gene has been found to be
      associated with left ventricular hypertrophy (LVH) in patients with essential
      hypertension (EHT) in certain populations. We sought to evaluate, in a Japanese
      population, whether ACE genotype is related to left ventricular mass, or to the
      geometry of LVH in EHT. Eighty-seven patients with EHT were examined. Their
      relative wall thickness (RWT) and left ventricular mass index (LVMI), determined
      by echocardiogram, were used to divide them into 4 groups: normal (normal RWT and
      LVMI, n = 35); concentric remodeling (increased RWT but normal LVMI, n= 10);
      eccentric hypertrophy (increased LVMI but normal RWT, n = 20); and concentric
      hypertrophy (increased LVMI and RWT, n = 22). Genetic analysis for ACE genotypes
      was performed on peripheral leukocytes using PCR techniques. Interventricular
      septal thickness and RWT were significantly greater in the patients with the DD
      genotype than in those with the II genotype, but LVMI did not differ among the
      three ACE genotypes. The frequency of the DD genotype was higher in the
      concentric hypertrophy group than in each of the other groups, and the frequency
      of the II genotype was lower in the concentric hypertrophy group than in either
      the normal or eccentric hypertrophy group. The geometric pattern of hypertensive
      LVH was associated with ACE genotype in a Japanese population. The DD genotype
      may contribute to concentric hypertrophy, but not to eccentric hypertrophy.

PMID- 10888380
TI  - Evaluation of right atrial appendage blood flow by transesophageal
      echocardiography in subjects with a normal heart.
AB  - Right atrial appendage (RAA) blood flow pattern was analyzed in 42 normal
      subjects-without cardiovascular disease (aged 30 to 48 years, mean 40 +/- 6) who
      underwent transesophageal echocardiography. RAA flow pattern was demonstrated to
      be bi-, tri- or quadriphasic and heart rate dependent (p < 0.01) in this study.
      In 15 subjects (36%), a biphasic pattern was observed. A triphasic pattern was
      observed in 12 subjects (28%). Fifteen subjects (36%) had a quadriphasic pattern.
      In these subjects, we observed a pattern consisting of two diastolic forward flow
      waves, each followed by a backward flow wave. Mean heart rates among subjects
      with bi-, tri- and quadriphasic patterns were 110 +/- 6, 91 +/- 4 and 72 +/- 13
      beats/min, respectively. In the triphasic pattern, the onset of superior vena
      cava diastolic forward flow began 18 +/- 4 ms after the onset of tricuspid E
      wave, whereas the first diastolic forward flow wave in the RAA began 40 +/- 7 ms
      after onset of the tricuspid E wave. A similar relation was also noted in the
      quadriphasic pattern. This sequence was constant and independent of heart rate (p
      < 0.05), suggesting a temporal relation between right ventricular relaxation and
      the first diastolic forward flow wave in the RAA. In normal subjects, the RAA
      flow pattern is heart rate dependent and three distinct flow patterns can be
      differentiated. Right ventricular relaxation appears to induce both the superior
      vena cava diastolic forward flow wave and the first diastolic forward flow wave
      of the RAA. These results can be used for comparison with patterns found in
      disease states.

PMID- 10888381
TI  - Potassium channel openers antagonize the effects of class III antiarrhythmic
      agents in canine Purkinje fiber action potentials. Implications for prevention of
      proarrhythmia induced by class III agents.
AB  - We studied the effects of potassium channel openers (PCOs) on frequency dependent
      prolongations of action potential duration (APD), triggered activities and
      oscillatory action potentials (OSC) induced by E-4031 and dofetilide. The action
      potentials of canine Purkinje fibers were recorded by a glass microelectrode
      technique. The effects of E-4031 (10(-6)M) as well as that of additional
      nicorandil (2 x 10(-5) M) on the APD were examined. When abnormal automaticity
      was observed under perfusion of E-4031 (10(-5) M) or dofetilide (10(-5) M),
      action potentials were recorded continuously to estimate the sequential effects
      of additional perfusion of nicorandil (6 x 10(-5) M) or Y-26763 (10(-5) M) on
      triggered activities and OSC. APD prolongation by E-4031 at slower stimulation
      rates (cycle lengths > or = 1,000 msec) was suppressed by nicorandil in a dose
      dependent manner. Both nicorandil and Y-26763 abolished the train of early
      afterdepolarization (EAD) due to E-4031 or dofetilide with a shifting of the
      resting membrane potential to a more negative level. PCOs also normalized
      dofetilide induced abnormal automaticities (EAD, OSC). The antagonistic actions
      of PCOs on changes in action potential induced by class III antiarrhythmic agents
      may prevent the development of proarrhythmias produced by these agents.

PMID- 10888382
TI  - Direct effects of class I antiarrhythmic drugs on epicardial electrograms in
      dogs.
AB  - The effects of class I antiarrhythmic drugs on epicardial electrograms during
      regular atrial pacing were investigated in anesthetized, open-chest dogs.
      Lidocaine, flecainide or disopyramide was infused selectively into the distal
      site of the left-anterior descending artery. Lidocaine produced a dose-dependent
      elevation of ST segment without changing the amplitude of R wave. Flecainide
      produced a dose-dependent increase of R-wave amplitude accompanied by the
      augmentation of negative T. The ST segment was elevated at the high dose. The
      QRST area did not change at the low dose but significantly increased at the high
      dose, indicating that the ST-T change at the low dose was secondary to changes in
      ventricular depolarization. The effects of disopyramide on R wave and ST segment
      were between those of lidocaine and flecainide. The major action of lidocaine was
      the acceleration of ventricular repolarization while that of flecainide was the
      deceleration of ventricular conduction. Disopyramide had an action that was
      intermediate between the two drugs.

PMID- 10888383
TI  - Augmented basal nitric oxide production contributes to maintenance of coronary
      blood flow in dogs with pacing-induced heart failure.
AB  - It remains controversial whether basal nitric oxide (NO) production in coronary
      resistance vessels in heart failure is enhanced or not. A transonic Doppler flow
      probe was placed around the left anterior descending coronary artery, and
      complete atrioventricular block was produced in fifteen dogs. The coronary
      pressure-flow relationships during long diastole were analyzed without and with
      pacing-induced heart failure. Three weeks after pacing at 240/min, plasma
      norepinephrine and renin activity significantly rose. Right atrial pressure and
      left ventricular end-diastolic pressure increased, and cardiac output and
      coronary perfusion pressure decreased; however, mean coronary blood flow did not
      change after pacing (55 +/- 5 to 52 +/- 5 ml/min/100 g, mean +/- SEM). The slope
      of the diastolic coronary pressure-flow relationship became steeper (1.22 +/-
      0.13 to 1.62 +/- 0.09 ml/min/100 g/mmHg, p < 0.05) with a slight increase in the
      measured zero-flow pressure (29.5 +/- 1.1 to 32.8 +/- 1.5 mmHg, p < 0.05) after
      pacing. After pretreatment with indomethacin, administration of NG-nitro-L
      arginine methyl ester caused an equal increase in the zero-flow pressure before
      (31.4 +/- 1.7 to 39.2 +/- 2.2 mmHg, p < 0.05) and after heart failure (33.9 +/-
      2.5 to 41.6 +/- 2.2 mmHg, p < 0.05), and more decline of the slope of the
      coronary pressure-flow relationship in heart failure (1.86 +/- 0.22 to 1.20 +/-
      0.05 ml/min/100 g/mmHg, p < 0.05) than before heart failure (1.11 +/- 0.12 to
      1.05 +/- 0.11 ml/min/100 g/mmHg, N.S.). This indicates that in failing hearts the
      vasodilatory action of NO in small vessels predominates despite the presence of
      several vasoconstricting factors. These results suggest that coronary blood flow
      is maintained despite detrimental hemodynamic and activated neurohumoral factors
      in the initial stage of heart failure, and that increased basal NO production
      plays a central role in the maintenance of basal coronary blood flow.

PMID- 10888384
TI  - Protective action of angiotensin converting enzyme inhibitors on cardiac
      hypertrophy in the aortic-banded rat.
AB  - Imidapril, enalapril and quinapril were subcutaneously administered to aortic
      banded rats by osmotic minipumps to compare the suppressive actions of these
      angiotensin converting enzyme (ACE) inhibitors on pressure-induced cardiac
      hypertrophy. Among the three drugs tested, imidapril was most potent for the
      prevention of cardiac hypertrophy, although equipotent hypotensive doses were
      used. Imidapril reduced both serum and cardiac ACE activities, while enalapril
      reduced only the former. Quinapril also reduced both, however, it was less potent
      at reducing the former compared to imidapril. Moreover, only imidapril
      significantly decreased left ventricular end diastolic pressure, which tended to
      be increased by aortic-banding. The lipophilicity of ACE inhibitors could not
      explain the more potent suppressive action of imidapril on cardiac hypertrophy
      because the lipophilicity of imidaprilat, an active metabolite of imidapril, was
      as low as an active metabolite of enalapril; i.e., much lower than an active
      metabolite of quinapril. The efficacy of ACE inhibitors on pressure-induced
      cardiac hypertrophy depends not only on an inhibitory effect on cardiac ACE
      activity, but also on other actions such as their effect on left ventricular end
      diastolic pressure.

PMID- 10888385
TI  - Slow-fast form of atrioventricular nodal reentrant tachycardia with eccentric
      retrograde left-sided activation.
AB  - A case of atypical AV nodal reentrant tachycardia (AVNRT) with eccentric
      retrograde left-sided activation, masquerading as tachycardia using a left-sided
      accessory pathway, is reported. Initially, it appeared that the tachycardia was a
      typical slow-fast form of AVNRT. The earliest retrograde activation, however, was
      registered at a site approximately 3 cm from the coronary sinus orifice (left
      atrial free wall), indicating atypical AVNRT. Atrial tachycardia and orthodromic
      AV reciprocating tachycardia using an accessory AV pathway were excluded. Slow
      pathway ablation at the posteroseptal right atrium eliminated the tachycardia. It
      was suggested that the anterograde limb of the tachycardia circuit was a slow AV
      nodal pathway with typical posteroseptal location, whereas the retrograde limb
      was a long atrionodal pathway connecting the compact AV node and the left atrial
      free wall near the mid-coronary sinus.

PMID- 10888386
TI  - Both low and high energy cardioversion induced accelerated ventricular
      tachycardia in a patient treated with an implantable cardioverter defibrillator.
AB  - A 72-year old male with an old myocardial infarction who had drug-refractory
      ventricular tachyarrhythmias received an implantable cardioverter-defibrillator
      (ICD). The patient did not take his prescribed beta-blocking agent for two days,
      following which he experienced six discrete shocks for spontaneous VT while
      riding his bicycle. Both 5J and 30J cardioversions were ineffective at
      terminating the VT and accelerated VT developed following the shocks. After
      admission, an electrophysiological study was performed while he was taking the
      beta-blocking agent, both low and high energy cardioversions reproducibly
      terminated the clinical VT without showing any accelerated rhythm. These findings
      suggest that the increase in sympathetic discharge may enhance the proarrhythmic
      potential of ICDs.

PMID- 10888387
TI  - Successful radiofrequency catheter ablation of incessant ventricular tachycardia
      with a delta wave-like beginning of the QRS complex.
AB  - Ventricular tachycardia with a delta wave-like beginning of the QRS complex is
      considered to be refractory to endocardial catheter ablation because it
      originates from the epicardial region. A 45-year-old woman had incessant
      ventricular tachycardia with a delta wave-like beginning of the QRS complex which
      was resistant to several antiarrhythmic drugs. The origin of the arrhythmia was
      at the mitral annulus on the antero-lateral left ventricular wall. The earliest
      endocardial activation preceded the QRS complex by 18 msec. After 7 sec of
      endocardial radiofrequency application ventricular tachycardia was terminated.
      During a 2 year follow-up ventricular tachycardia did not recur and only small
      numbers of premature ventricular contractions (< 100/day) were noted. VT with
      delta wave-like QRS morphology which originates from the basal region of the
      ventricle may be treated successfully with radiofrequency catheter ablation using
      an endocardial approach.

PMID- 10888388
TI  - Brady-tachycardia syndrome after radiotherapy for lung cancer. Assessment by
      computed tomography and carbon-11 methionine positron emission tomography.
AB  - A 74-year-old male who had received radiotherapy (total 54 Gy) for right lung
      cancer 7 months earlier developed a symptomatic brady-tachycardia syndrome
      requiring the implantation of a permanent pacemaker. Chest CT showed a pulmonary
      tumor of 2-cm diameter in the right lower lobe with direct extension into the
      surrounding tissue, suggesting the possibility of cardiac invasion. Carbon-11
      methionine positron emission tomography (PET) indicated the absence of visible
      invasion of the heart with lung cancer. The bradytachycardia syndrome, therefore,
      was considered to be associated with sinus node injury due to radiation. Carbon
      11 methionine PET metabolic imaging might play an important role in evaluating
      noninvasively the cause of the arrhythmia in this patient.

PMID- 10888389
TI  - Effect of endothelial dysfunction on regional perfusion in myocardial territories
      supplied by normal and diseased vessels in patients with coronary artery disease.
AB  - BACKGROUND: Endothelium-dependent regulation of coronary tone affects both
      conduit and resistance coronary arteries. However, little is known about the
      usefulness of myocardial perfusion imaging in evaluating coronary endothelial
      function. We evaluated the relation between invasive angiographic measurements of
      coronary vasomotion in response to intracoronary acetylcholine and the presence
      of regional perfusion abnormalities assessed by technetium 99m sestamibi imaging.
      METHODS AND RESULTS: We studied 11 patients (9 men and 2 women) with suspected
      coronary artery disease (48 +/- 8 years, mean +/- standard deviation). We used
      quantitative coronary angiography to delineate the vasomotor response to
      increasing doses of acetylcholine given intracoronary. Regional myocardial
      perfusion was assessed by planar Tc-99m sestamibi imaging during and after the
      administration of acetylcholine. In the 11 patients, 23 coronary artery
      territories were analyzed: 13 were angiographically normal, and 10 showed varying
      degrees of luminal narrowing. Four (31%) of 13 angiographically normal coronary
      arteries had a positive vasomotor response to acetylcholine (> or =20% reduction
      in luminal diameter) that was associated with a regional perfusion defect.
      Acetylcholine induced a positive vasomotor response, which was also associated
      with a regional perfusion defect in 1 of 3 coronary arteries with stenoses of
      intermediate severity (50% to 69%). Likewise, acetylcholine induced a positive
      vasomotor response in 6 of 7 coronary arteries with significant luminal narrowing
      (> or =70%), 5 of which showed a corresponding regional perfusion defect.
      CONCLUSIONS: In patients with coronary artery disease, noninvasive measurements
      of regional myocardial perfusion by Tc-99m sestamibi correlate well with invasive
      measurements of coronary endothelial function. These findings may have
      implications for monitoring the effects of interventions designed to improve
      endothelial function and microvascular function in patients with coronary artery
      disease.

PMID- 10888390
TI  - Stress perfusion/metabolism imaging: a pilot study for a potential new approach
      to the diagnosis of coronary disease in women.
AB  - BACKGROUND: The diagnosis of coronary artery disease (CAD) in women continues to
      be a challenge. F-18 deoxyglucose (FDG) positron emission tomography (PET) has
      been used for detection of myocardial ischemia at rest. Little has been reported
      about FDG stress imaging. The aim of this pilot study was to assess stress FDG
      PET imaging for defining CAD in a group of women referred for chest pain.
      METHODS: Stress FDG imaging was performed in 19 women (mean age 59 +/- 10 years).
      All had abnormal stress testing before entering the study. FDG and 2-methoxy-2
      methylpropyl isonitrile were injected at peak stress (treadmill n = 8,
      dipyridamole n = 11) followed by PET and single photon emission computed
      tomography image acquisitions. Myocardial ischemia was defined by regions that
      demonstrated both a defect on perfusion imaging and increased FDG uptake relative
      to uptake in normal perfusion zones. Defect/normal zone FDG ratios were also
      determined. Coronary angiography was performed on all patients. RESULTS: Average,
      or mean, body mass index was high at 29.2 +/- 5 kg/m2. Nine of 19 patients had
      significant CAD. Eight of 9 with CAD had FDG-defined ischemia. Nine of the 10
      without CAD had negative FDG images (sensitivity 89%, specificity 90%). The
      average defect/normal zone FDG ratio was greater in patients with CAD than in
      those without (2.4 +/- 1.9 vs 0.9 +/- 0.4, P < .05). CONCLUSIONS: Regional FDG
      uptake in areas of perfusion defects with stress increased in this group with
      CAD. These pilot data suggest that stress FDG PET may be diagnostically helpful
      in obese female patients. This novel approach may complement current methods of
      CAD detection in women and warrants further study.

PMID- 10888391
TI  - Accuracy of dipyridamole SPECT imaging in identifying individual coronary
      stenoses and multivessel disease in women versus men.
AB  - BACKGROUND: Older women frequently undergo dipyridamole perfusion imaging and can
      have advanced coronary artery disease, but little data exist on the accuracy of
      perfusion imaging in detecting disease in individual vascular territories and
      multivessel disease in women, compared with men. METHODS AND RESULTS: From a
      database of patients undergoing myocardial single photon emission computed
      tomography (SPECT) perfusion imaging, 107 unselected sequential patients (58
      women, 49 men) who underwent sestamibi dipyridamole stress and cardiac
      catheterization within 6 months of each other were identified. Data were analyzed
      to compare sensitivities for detection of individual coronary stenoses and
      multivessel disease. The concordance between perfusion image results and cardiac
      catheterization for individual coronary territories for women was 75%, and for
      men, it was 65% (P = .09). In women, the presence of disease of the left anterior
      descending coronary artery was detected more frequently than it was in men, 84%
      versus 44% (P = .004). The detection of disease in the territories of the left
      circumflex and right coronary arteries was similar for both groups. For women,
      the accuracy of perfusion imaging in identifying the presence/absence of
      multivessel coronary disease was 64%, compared with 71 % for men (P = not
      significant). CONCLUSIONS: The accuracy of dipyridamole sestamibi SPECT imaging
      in detecting multivessel disease was similar for men and women. The sensitivity
      of dipyridamole sestamibi SPECT imaging in detecting disease of the left anterior
      descending artery was better in women.

PMID- 10888393
TI  - Regional myocardial oxygen consumption estimated by carbon-11 acetate and
      positron emission tomography before and after repetitive ischemia.
AB  - BACKGROUND: Preserved myocardial oxygen consumption estimated by carbon 11
      acetate and positron emission tomography (PET) in myocardial regions with chronic
      but reversibly depressed contractile function in patients with ischemic heart
      disease have been suggested to be caused by repeated short episodes of acute
      myocardial ischemia. To evaluate this hypothesis myocardial 11C-acetate PET
      imaging was performed before and after acute repetitive myocardial ischemia.
      METHODS AND RESULTS: In open chest dogs (n = 8), the left anterior descending
      coronary artery was occluded 4 times for 5 minutes alternating with 5 minutes of
      reperfusion. Before and after repetitive coronary occlusions, oxygen 15
      water/oxygen 15 carbon monoxide (blood flow), and 11C-acetate (oxygen
      consumption) PET imaging were performed. Left ventricular regional systolic wall
      thickening was measured with sonomicrometry. Forty-five minutes after the
      ischemic episodes, systolic ventricular wall thickening was decreased by 90%,
      whereas myocardial blood flow was reduced by 21% compared with baseline values (P
      < .05). Ninety minutes after the ischemic episodes, estimated oxygen consumption
      was unaltered compared with the baseline level despite a sustained 70% decrease
      in the regional contractile function (P < .05). CONCLUSIONS: Oxygen consumption
      estimated by 11C-acetate PET imaging is preserved after repeated episodes of
      acute myocardial ischemia despite a severe impairment of contractile function.

PMID- 10888392
TI  - Feasibility of planar myocardial carbon 11-acetate imaging.
AB  - BACKGROUND: Myocardial oxygen consumption can be determined by using carbon 11
      acetate (11C-acetate) and positron emission tomography (PET). The aim of this
      study was to validate planar 11C-acetate scintigraphy in healthy individuals by
      relating the myocardial clearance rate of dynamic 11C-acetate scintigraphy with
      the rate-pressure product, which is used as a measure of cardiac work. Also, the
      optimal curve-fitting procedure of the time-activity curve and the intraobserver
      and interobserver variation of determining the clearance rates were assessed.
      METHODS AND RESULTS: Six subjects were studied at rest, and seven subjects were
      studied during dobutamine stimulation. Imaging was performed with a planar camera
      equipped with high-energy collimators for 45 minutes after the injection of 185
      MBq of 11C-acetate. Myocardial time-activity curves were corrected for decay.
      During the study, heart rates and blood pressures were measured to calculate the
      rate-pressure product. Myocardial time-activity curves showed a clear biphasic
      pattern. Clearance rates were expressed in k values. The best fitting procedure,
      as assessed by means of the lowest error of k and the best correlation with the
      rate-pressure product, proved to be a monoexponential fit on the first part of
      the time-activity curve (kmono). Subjects studied during dobutamine infusion had
      significantly higher rate-pressure product (15.0 +/- 2.1*10(3) vs 8.6 +/-
      1.2*10(3), P < .001) and 11C-acetate clearance rates (kmono = 0.0657 +/- 0.0110
      vs 0.0313 +/- 0.0056, P < .0001) than subjects studied at rest. There was low
      intraobserver and interobserver variation in determining kmono values. A
      significant correlation between the rate-pressure product and the monoexponential
      clearance rate was found (kmono = 5.11*10(-6)*RPP-0.012; r = 0.94, P < .001).
      CONCLUSIONS: The estimation of myocardial oxygen consumption is feasible with
      planar 11C-acetate scintigraphy. Clearance rates and the relation with the rate
      pressure product are similar to those reported in PET studies. This technique may
      be used for the assessment and follow-up of global myocardial metabolic
      abnormalities, eg, in patients with hypertensive heart disease, cardiomyopathy,
      myocarditis, and valvular disease.

PMID- 10888394
TI  - Technetium 99m furifosmin regional myocardial uptake in patients with previous
      myocardial infarction: relation to thallium-201 activity and left ventricular
      function.
AB  - BACKGROUND: This study was designed to compare the results of rest-redistribution
      thallium-201 imaging with those of rest technetium 99m furifosmin single photon
      emission computed tomography in the same patients with chronic ischemic left
      ventricular (LV) dysfunction. METHODS: Twenty-one patients (mean age 62 +/- 9
      years) with chronic myocardial infarction and LV dysfunction (mean LV ejection
      fraction 34% +/- 8%) underwent rest-redistribution thallium imaging and resting
      furifosmin single photon emission computed tomography on the same day. In each
      patient, regional thallium and furifosmin activity was quantitatively measured in
      13 myocardial segments. Regional LV function was assessed in corresponding
      segments by echocardiography. RESULTS: At thallium imaging, 91 (33%) segments had
      normal uptake, 16 (6%) showed reversible defects, and the remaining 166 (61%)
      irreversible defects. Of these 166 irreversible defects, 74 (45%) had moderate (>
      or =58% of peak activity) and 92 (55%) severe (<58% of peak activity) reduction
      of thallium uptake. Regional furifosmin uptake was significantly related to both
      rest (r = 0.87, P < .0001) and redistribution (r = 0.90, P < .0001) thallium
      activity. Agreement in the evaluation of regional perfusion status between
      thallium and furifosmin imaging was observed in 70% of the 84 hypokinetic
      segments (kappa = 0.54) and in 76% of the 78 akinetic or dyskinetic segments
      (kappa = 0.60). Concordance in the detection of myocardial viability between
      thallium and furifosmin imaging was observed in 69 (82%) of hypokinetic regions
      (kappa = 0.60) and in 65 (83%) of akinetic or dyskinetic regions (kappa = 0.67).
      CONCLUSIONS: These results suggest that in patients with chronic coronary artery
      disease and LV dysfunction, quantitative rest-redistribution thallium
      scintigraphy and furifosmin tomography at rest provide similar results in the
      evaluation of perfusion status and in the detection of myocardial viability.

PMID- 10888396
TI  - Exercise equilibrium radionuclide angiography predicts long-term cardiac
      prognosis in patients with abdominal aortic aneurysm being considered for
      surgery.
AB  - BACKGROUND: Patients with an abdominal aortic aneurysm (AAA) have a high
      prevalence of coronary disease and are at risk for cardiac events. This may
      offset the prognostic benefit of surgical repair. We investigated whether
      preoperative exercise equilibrium radionuclide angiography (ERNA) could be used
      to identify patients at high risk for cardiac events after successful AAA repair.
      METHODS: Between 1990 and 1995, 173 patients with an AAA were referred for supine
      bicycle exercise ERNA preoperatively. Follow-up information was obtained from a
      questionnaire sent to each patient's family physician. Cardiac events were
      defined as cardiac death or nonfatal myocardial infarction. RESULTS: A total of
      139 patients were able to exercise and did not die or suffer myocardial
      infarction perioperatively. The median follow-up period was 3.8 years. Diabetes
      mellitus, an exercise ejection fraction (EF) below 0.50, and a fall in EF with
      exercise were univariable predictors of cardiac risk during the follow-up period
      (P < .05). On multivariable analysis, diabetes mellitus (risk ratio [RR], 6.9;
      95% CI 1.5 to 32.0) and an EF fall (RR, 4.1; 95% CI 1.5 to 11.4) emerged as the
      most important predictors. CONCLUSIONS: Exercise ERNA predicts long-term cardiac
      events in patients being considered for elective AAA repair. Such predictive
      information may influence the decision to operate, for example, on small
      unthreatening aneurysms, or lead to invasive cardiological management to minimize
      risk.

PMID- 10888395
TI  - Role of insulin resistance in heart and skeletal muscle F-18 fluorodeoxyglucose
      uptake in patients with non-insulin-dependent diabetes mellitus.
AB  - BACKGROUND: Altered heart and skeletal glucose usage has been reported in
      patients with non-insulin-dependent diabetes mellitus (NIDDM). Although
      elevations in plasma free fatty acid (FFA) concentrations have been implicated in
      reduced myocardial 18fluorine-fluoro-2-deoxy-D-glucose uptake (MFU), the specific
      role of whole-body insulin resistance in MFU in patients with NIDDM compared with
      skeletal muscle metabolism remains controversial. PURPOSE: MFU and skeletal
      muscle 18fluorine-fluoro-2-deoxy-D-glucose uptake (SMFU) were compared with
      positron emission tomography and the whole-body glucose disposal rate (GDR)
      during hyperinsulinemic euglycemic clamping in 26 normotensive asymptomatic
      patients with NIDDM who were not taking medication. These factors were also
      compared in 12 age-matched control subjects to increase the knowledge of the
      influence of whole-body insulin resistance on MFU. In addition, independent
      factors for both SMFU and MFU were investigated. RESULTS: GDR in control subjects
      (10.0 +/- 2.97 mg/min per kilogram) was significantly higher than in patients
      with NIDDM (4.05 +/- 2.37 mg/min per kilogram, P < .01). SMFU in patients with
      NIDDM (0.826 +/- 0.604 mg/min per 100 g) was significantly lower than that in
      control subjects (1.86 +/- 1.06 mg/min per 100 g, P < .01). MFU in patients with
      NIDDM (5.35 +/- 2.10 mg/min per 100 g) was also significantly lower than that of
      control subjects (7.05 +/- 1.66 mg/min per 100 g, P = .0182). SMFU significantly
      correlated with GDR (r = .727, P < .01) and FFA (r = -.52, P < .01) in patients
      with NIDDM. MFU also correlated with GDR (r = .778, P < .01) and FFA (r = -.72, P
      < .01) in patients with NIDDM. Multivariate stepwise regression analysis showed
      that GDR (F = 36.8) was independently related to MFU (r = .85, P < .01) whereas
      FFA was not (F = 1.763), where F is the value for statistical analysis of
      multivariate stepwise regression analysis. CONCLUSION: Insulin resistance is the
      most essential factor for both heart and skeletal muscle FDG uptake in patients
      with NIDDM.

PMID- 10888397
TI  - Experimental validation of a new coronary guide wire labeled with rubidium
      81/krypton 81m for continuous assessment of myocardial blood flow.
AB  - BACKGROUND: The rubidium 81/krypton 81m method was suggested for assessment of
      myocardial blood flow (MBF) three decades ago. This study investigates the novel
      concept of using 81Rb-/81mKr-labeled coronary guide wires with wire-attached 81Rb
      activity and diffusable 81mKr gas for assessment of lesion-specific impairment of
      MBF by evaluation of the 81Rb/81mKr activity ratio. The feasibility of wire
      production is tested, and application of the method is investigated in the canine
      model. METHODS AND RESULTS: Conventional coronary guide wires for angioplasty
      (0.014 in) were labeled with radioactive 81Rb/81mKr by ion bombardment of the
      wire tip. A total of 16 of the 18 wires labeled in series showed successful 81Rb
      fixation in combination with free 81mKr gas diffusability during quality control
      measurements. The suitability of the wires to assess MBF in combination with an
      external gamma ray detector was investigated in open-chested dogs.
      Electromagnetic measurement of coronary blood flow (CBF) was used as reference,
      providing a signal that is directly linked to volumetric MBF. The 81Rb/81mKr
      ratio tracked changes in CBF reliably in all 6 dogs. The found linear dependence
      of measured 81Rb/81mKr count rates on measured CBF supports the modeling
      assumptions made to apply the theoretic basis of the 81Rb/81mKr technique to 81Rb
      labeled coronary guide wires. CONCLUSION: 81Rb-/81mKr-labeled coronary guide
      wires provide a signal that indicates volumetric MBF directly. This unique
      capability may qualify the technique as a valuable tool for research purposes and
      as an attractive method for invasive cardiology at centers where the logistic
      arrangements for short-lived isotope supply are provided.

PMID- 10888398
TI  - Statistical analysis of medical data. Part II.

PMID- 10888400
TI  - Nuclear cardiology technology: historical perspectives and future directions.

PMID- 10888399
TI  - Cellular and molecular regulation of cardiac glucose transport.

PMID- 10888401
TI  - Nuclear imaging and endothelial dysfunction.

PMID- 10888402
TI  - Use of carbon 11-acetate for the measurement of myocardial oxygen consumption.

PMID- 10888403
TI  - Exercise-induced myocardial ischemia: can this be imaged with F-18
      fluorodeoxyglucose?

PMID- 10888404
TI  - Extracardiac localization of technetium 99m sestamibi.

PMID- 10888405
TI  - Nuclear cardiology in the literature.

PMID- 10888406
TI  - Changes of transmembrane Ca2+ gradient in the formation of macrophage-derived
      foam cells.
AB  - Macrophages from C57BL/6J mice, an animal susceptible to atherosclerosis, were
      chosen as target cells to study changes in the transmembrane Ca2+ gradient during
      the formation of macrophage-derived foam cells. The transmembrane Ca2+ gradients
      of single living cells were examined-using Fura-2/AM combined with Fluo-3/AM by
      laser scanning confocal microscopy. Exposure to Oxidized Low Density Lipoprotein,
      decreases the Ca2+ gradient across macrophage plasma membrane, but increases that
      across the nuclear membrane. The altered transmembrane Ca2+ gradients could
      induce the up-regulation of scavenger receptor in macrophages, resulting in the
      formation of foam cells.

PMID- 10888407
TI  - Chloramphenicol and ampicillin-induced changes in rat hepatic esterase and
      amidase activities.
AB  - The influence of ampicillin and chloramphenicol administered intraperitoneally
      singly or in combination on the protein content and the activities of hepatic
      esterase and amidase have been investigated in rats. The results have been
      compared to the effects of phenobarbitone (inducer) and p-nitrophenyl-phosphate
      (inhibitor) of hepatic hydrolases. Ampicillin pretreatment reduced protein level
      and amidase activity by 3.5% each but caused a significant increase (8.1%) in
      total esterase activity compared to controls. Chloramphenicol treatment caused an
      overall decrease in protein level, esterase and amidase activities respectively
      by 11%, 11%, and 35% over controls. Combined administration of both drugs
      resulted in a decrease in protein, esterase and amidase activities by 11.5%,
      12.5%, and 41.2% respectively, thus mimicking the effects obtained with
      chloramphenicol alone. The changes induced by administration of the drugs
      particularly in combination on the constituent enzymes of rat hepatic hydrolases
      may affect the ability of the body to deal with exposure to environmental
      chemicals if extrapolated to man.

PMID- 10888408
TI  - Fluorescent properties of firefly luciferases and their complexes with luciferin.
AB  - Fluorescence of luciferases from Luciola mingrelica (single tryptophan residue,
      Trp-419) and Photinus pyralis (two tryptophan residues, Trp-417, Trp-426) was
      studied. Analysis of quenching of tryptophan fluorescence showed that the
      tryptophan residue conserved in all luciferases is not accessible for charged
      quenchers, which is explained by the presence of positively and negatively
      charged amino acid residues in the close vicinity to it. An effective energy
      transfer from tryptophan to luciferin was observed during quenching of tryptophan
      fluorescence of both luciferases with luciferin. From the data on the energy
      transfer, the distance between the luciferin molecule and Trp-417 (419) in the
      luciferin luciferase complex was calculated: 11-15 A for P. pyralis and 12-17 A
      for L. mingrelica luciferases. The role of the conserved Trp residue in the
      catalysis is discussed.

PMID- 10888409
TI  - A study of membrane activity in rat prostate cancer cells: an evaluation of the
      FM1-43 dye technique.
AB  - A study was initiated to test whether the FM1-43 dye technique could be applied
      to the study of endocytic membrane activity in two rodent prostate cancer (MAT
      LyLu and AT-2) cell lines of markedly different metastatic ability. The
      lipophilic dye FM1-43, which has frequently been used to monitor endo/exocytic
      activity in excitable cells was employed. We found, as in excitable tissues, that
      both strongly metastatic (MAT-LyLu) and weakly metastatic (AT-2) cells in culture
      take up FM1-43 to give vesicular staining of a variable pattern, which appeared
      to differ between the two cell lines. However, unlike excitable tissues, neither
      cell line subsequently released the dye. Indeed, both cell lines retained the dye
      through several rounds of cell division suggesting that dye incorporated by cells
      does not enter the endo/exocytotic cycle. Uptake of dye was independent of
      temperature, Na+/K+ gradients, pH or metabolism. We suggest that passive
      accumulation of FM1-43 can occur in cancer cells and should not, automatically,
      be interpreted as evidence of endocytosis.

PMID- 10888410
TI  - Increased stability and catalytic efficiency of yeast hexokinase upon interaction
      with zwitterionic micelles. Kinetics and conformational studies.
AB  - The effect of ligands (glucose, ATP and Mg2+) and zwitterionic micelles of
      lysophosphatidylcholine (LPC) or N-hexadecyl-N,N-dimethyl-3-ammonium
      propanesulfonate (HPS) in the yeast hexokinase (HK) stability was studied at 35
      degrees C. The thermal inactivation kinetics followed one-exponential decay. The
      effect of ligands on protecting the enzyme against inactivation followed the
      order: glucose > glucose/Mg2+ >ATP/Mg2+ approximately or approximately equal to
      Mg2+l approximately or approximately equal to buffer only. Both LPC and HPS
      micelles increased the enzyme stability only when the incubation medium contained
      glucose or glucose/Mg2+, suggesting that the protein conformation is a key
      prerequisite for the enzyme-micelle interaction to take place. This enzyme
      micelle interaction resulted in an increased catalytic efficiency (with a
      decrease in Km for ATP and increase in Vmax as well as in changes on the tertiary
      (intrinsic fluorescence) structure of the yeast hexokinase.

PMID- 10888412
TI  - Strategies offering protection from the toxic effects of anticancer treatments
      with a focus on chemoprotective agents.
AB  - Side effects associated with chemotherapy and radiotherapy affect mainly a
      patient's quality of life. Means or agents designed to alleviate toxicities of
      anticancer treatments have been marketed or are under active investigation. In
      this paper, we review the reports published in this field in 1999.

PMID- 10888411
TI  - A new class of antiemetics: the NK-1 receptor antagonists.
AB  - Emesis is one of the most unpleasant and debilitating side effects of anticancer
      chemotherapy. In acute emesis (vomiting occurring 0-24 hours after chemotherapy
      administration), the 5-HT3 receptor antagonists and corticosteroids are highly
      effective, with few significant side effects, and can safely be combined. Delayed
      emesis (vomiting occurring >24 hours after chemotherapy administration), however,
      is both not well understood and less well controlled. Studies have yielded
      conflicting results concerning the use of 5-HT3 receptor antagonists alone in
      delayed emesis. The data of NK-1 receptor antagonists in the control of acute
      emesis, although promising, need confirmation in a properly designed study.

PMID- 10888413
TI  - Clinical benefit from erythropoietin.
AB  - Advances continue in erythropoietin biology, and additional data reviewed here
      have recently become available on complex feedback mechanisms describing the
      interrelations of hypoxia and its effects on anemia and tumor behavior (eg,
      apoptosis, angiogenesis). In addition to biology, other clinically relevant data
      in oncology are included and an attempt is made to identify patients who are most
      likely to benefit from treatment. The latter aspects will better define the
      profile of the target patient, probably prevent overtreatment, and improve cost
      benefit ratios. Interesting data on radiotherapy results improved by increasing
      tissue hemoglobin have been published but will need further confirmation.

PMID- 10888414
TI  - Indications and complications of intravenous devices for chemotherapy.
AB  - Vascular access devices (VADs) are frequently used in patients with cancer.
      Vascular access devices can be divided into external catheters and subcutaneous
      venous access ports. Each type of device has its advantages and disadvantages,
      but the indications and optimal use of specific VADs remain to be defined. There
      are multiple complications of VADs but, with the exception of catheter-related
      bloodstream infections and thrombosis, most complications are rare. The use of
      VADs impregnated with antibiotic reduces the rates of catheter colonization and
      catheter-related bloodstream infections as compared with the use of unimpregnated
      catheters for short-term use. Thrombosis remains a major complication of VADs,
      and prospective, controlled studies are needed to clearly define the risk
      factors, natural history, and optimal treatment of this complication.

PMID- 10888415
TI  - Opioid switch to oral methadone in cancer pain.
AB  - The occurrence of undesirable side effects due to opioids (delirium, confusion,
      myoclonus, nausea, emesis) is one of the major complications in the management of
      pain, especially in chronic cancer pain states. Methadone, as an alternative to
      morphine, has been proposed in the control of opioid-induced toxicity. Methadone
      is a synthetic opioid, with mu and delta receptor activity, associated with the
      capacity to inhibit N-methyl-D-aspartate receptors. Questions have arisen
      concerning its equianalgesic ratio since its rediscovery over the past few years
      and are certainly related to its receptor interactions. Aspects of its
      pharmacology, indications, and switching modalities are discussed here. Opioid
      rotation is a new tool in the management of cancer pain, deserving more
      attention.

PMID- 10888416
TI  - Cytogenetics and the biologic basis of sarcomas.
AB  - In this past year, a large number of reports have described cytogenetic and
      biologic studies of sarcomas. The cytogenetic studies provide further evidence
      that a growing number of sarcomas seem to be defined by consistent chromosomal
      abnormalities that can be detected using a variety of molecular genetic tests.
      However, in addition to these specific abnormalities, many sarcomas have other
      extremely complex genetic changes. This complexity has made it quite difficult to
      understand the importance of any single abnormality. Laboratory studies
      complementing these genetic studies have provided further understanding of
      sarcoma cellular and molecular biology. Importantly, both types of studies have
      had significant impact in the clinic in the form of more objective diagnostic
      tests, potential novel prognostic markers, and even new therapeutic strategies.
      Together, these papers highlight how genetic studies may offer tremendous insight
      into sarcoma biology. However, they also highlight some limitations of these
      approaches as well. Novel experimental approaches may be required to facilitate
      the continued progress in this field toward the development of better therapeutic
      strategies.

PMID- 10888417
TI  - Ewing sarcoma family of tumors.
AB  - The Ewing sarcoma family of tumors (ESFT) shares a common neural histogenesis,
      tumor genetics, and a fascinating biology, all of which hold the promise of
      identifying new therapeutic targets. The genetic hallmark of ESFT is the presence
      of the t(11;22)(q24;q12), which creates the EWS/FLI1 fusion gene and results in
      the expression of a chimeric protein. This article reviews much of the important
      work that has been reported over the past year regarding the biology and therapy
      of ESFT. Major studies include the observation that the early region (E1A) of
      human adenovirus type 5 is directly linked to and may initiate production of the
      EWS/FLI1 fusion transcript in normal human fibroblasts and keratinocytes. In
      addition, there is new information regarding the function of EWS/FLI1 and
      downstream signals by which it acts. New clinical information continues to
      support the addition of ifosfamide to standard chemotherapy regimens and help
      further refine prognostic features, including biologic features that may someday
      allow better risk stratification and therapy design.

PMID- 10888418
TI  - Osteosarcomas and other cancers of bone.
AB  - The results of several studies suggest that alterations in various cell cycle
      regulatory genes are involved in the pathogenesis of osteosarcomas. Experiments
      in animal models provide preliminary data on the feasibility of gene therapy in
      osteosarcoma and chondrosarcoma. Prediction of response to chemotherapy remains a
      major focus of imaging research. Several clinicopathologic studies have explored
      the mechanisms underlying multidrug resistance in osteosarcoma patients receiving
      neoadjuvant chemotherapy. HER2/erbB2 expression, linked to poor prognosis, has
      been proposed as a therapeutic target in osteosarcoma. In clinical studies of
      osteosarcoma, further data confirm the activity of ifosfamide and carboplatin but
      provide little support for the use of immunotherapy. A retrospective analysis
      showed no value for dose intensification of doxorubicin/cisplatin, but the
      results of a prospective trial should be more informative. Recent evidence
      confirms that secondary osteosarcomas and malignant fibrous histiocytomas of bone
      should be treated with aggressive chemotherapy regimens, similar to those used
      for osteosarcomas.

PMID- 10888419
TI  - Rhabdomyosarcoma and soft tissue sarcoma in childhood.
AB  - The past year has seen a greater understanding of the means by which the alveolar
      rhabdomyosarcoma gene fusions (PAX-FKHR) lead to the malignant phenotype. The
      treatment of the primary tumor in rhabdomyosarcoma has been reexamined, with the
      roles of surgery and radiation expanding in American studies and decreasing in
      European ones. "Megatherapy" approaches with stem cell or bone marrow autologous
      transplants still have not found a role in the treatment of metastatic
      rhabdomyosarcoma. Our understanding of the natural history of nonrhabdo soft
      tissue sarcomas in children has increased, and molecular diagnosis is becoming
      established. The role of chemotherapy in treatment remains controversial.

PMID- 10888420
TI  - Anal carcinoma: histology, staging, epidemiology, treatment.
AB  - Our understanding of the pathogenesis and management of squamous cell carcinoma
      of the anal canal has undergone profound change over the last 30 years.
      Epidemiologic studies have demonstrated that infection with human papillomavirus
      is most likely responsible for the majority of cases. Primary treatment with
      concomitant chemotherapy and radiation cures the majority of patients without the
      need for an abdominoperineal resection. Recent series have demonstrated that
      approximately one half of patients with a local recurrence after chemoradiation
      will be cured with salvage surgery. The incorporation of cisplatin into the
      primary chemoradiation treatment of patients with carcinoma of the anal canal is
      the focus of current studies.

PMID- 10888421
TI  - Surgical salvage therapy: abdominoperineal resection for recurrent anal
      carcinoma, metastasectomy of recurrent colorectal cancer, and esophagectomy after
      combined chemoradiation.
AB  - This review highlights the advances in the salvage surgical therapies for
      recurrent disease after definitive therapy of anal carcinoma, colorectal cancer,
      including liver metastasectomy, and esophageal carcinoma treated primarily with
      chemoradiation. New diagnostic modalities, advances in neoadjuvant therapies for
      unresectable liver metastases, and, in addition, the importance of adjuvant
      hepatic arterial chemotherapy after curative liver resections are reviewed.
      Although chemoradiation is not the standard of care for esophageal cancer,
      salvage esophagectomy after such treatment is discussed. Definitive
      chemoradiation for squamous cell carcinoma of the anus has altered the role of
      surgical intervention to a salvage option instead of primary treatment. Although
      this is not yet the case for esophageal carcinoma, recent improved chemoradiation
      regimens have been reported by the French and Japanese, who use surgery for
      nonresponders. For recurrent colorectal carcinoma, including liver-only
      metastases, patients can be rendered disease free after surgical extirpation with
      evidence of improved survival. Appropriate surveillance in these patients may
      identify subsets of patients with disease amenable to resection.

PMID- 10888422
TI  - Hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a disease that is extremely difficult to manage
      and is increasing markedly in incidence. This presents both an opportunity and a
      challenge. At-risk patients can be identified and early detection of HCC is
      feasible. New surgical techniques and postoperative therapies, including hepatic
      intra-arterial radiation, may improve the outlook for some patients with
      resectable cancer. Unfortunately, the vast majority of patients with HCC will
      have unresectable cancers. Regional treatments may shrink or necrose tumors, but
      no clear benefit to such therapies has been demonstrated. Recent evidence
      suggests combination chemotherapy may help some patients, although this needs
      validation. Perhaps the best hope is that the further elucidation of the genetic
      and molecular features of HCC will lend us insight into innovative strategies to
      manage this difficult cancer.

PMID- 10888423
TI  - Recent meta-analyses in colorectal cancer.
AB  - Meta-analyses play an important role in the current emergence of evidence-based
      medicine. This paper reviews the meta-analyses reported in the past 3 years in
      colorectal cancer, from a clinical as well as a statistical perspective. The
      usefulness of meta-analyses in our understanding and management of colorectal
      cancer is highlighted for screening, risk of colorectal cancer occurrence,
      outcome of colorectal cancer, adjuvant treatment, follow-up, and treatment of
      advanced disease.

PMID- 10888425
TI  - Bibliography. Current world literature. Supportive care.

PMID- 10888424
TI  - Carcinoid and pancreatic endocrine tumors: recent advances in molecular
      pathogenesis, localization, and treatment.
AB  - Neuroendocrine tumors include carcinoids and pancreatic endocrine tumors, which
      share a number of common features in their pathology, ability to cause clinical
      symptoms due to ectopic hormone and bioamine release, localization methods, and
      treatment. Although generally slow growing, a proportion demonstrate aggressive
      tumor growth. Therefore, in many cases treatment must be directed against both
      the tumor and the hormone-excess state. There have been significant recent
      advances into their molecular pathogenesis, natural history, and prognostic
      factors; clinical presentation defined by larger series analysis; localization
      methods; and the development of new treatments directed against the tumor and to
      control the hormone-excess state (including depot somatostatin analogues,
      interferon combinations, embolization, chemoembolization, radiotherapy with novel
      somatostatin analogues, and liver transplantation). Recent advances in each of
      these areas are briefly discussed.

PMID- 10888426
TI  - Bibliography. Current world literature. Sarcomas.

PMID- 10888427
TI  - Bibliography. Current world literature. Gastrointestinal tract.

PMID- 10888428
TI  - Spectral and thermal studies of thiobarbituric acid complexes.
AB  - The complexes of 2-thiobarbituric acid with Fe(II), Fe(III), Co(II), Cu(II),
      Zn(II) and Cd(II) have been isolated and characterized on the basis of elemental
      analyses, molar conductance, magnetic moment and spectral studies. The thermal
      decomposition of the metal complexes was studied by TG and DTA techniques. The
      kinetic parameters namely, activation energy, entropy of activation and the
      reaction orders were estimated.

PMID- 10888429
TI  - Correction for quenching in fluorimetric determinations using steady state
      fluorescence.
AB  - Quenching corrections in fluorimetric estimations are arrived at using time
      resolved fluorometry, where the reduction in the lifetimes of the fluorophore in
      the presence of quenchers is a measure of the correction. A novel procedure for
      the correction of quenching in fluorimetric determinations using steady state
      fluorescence spectroscopy is described here. The method is based on the variation
      in the slope of the fluorescence versus concentration plots, as the quencher
      concentration is changed. As a test case, the procedure for the determination of
      uranium has been demonstrated in the presence of a number of metal ion quenchers.

PMID- 10888430
TI  - Characterization of potassium and sodium-potassium alloy solutions containing
      metal anions and complexed cations by means of NMR and ESR techniques.
AB  - The influence of a complexing agent, kind of solvent and temperature on the
      stability and ionic composition of potassium and sodium-potassium alloy solutions
      containing metal anions and complexed cations as well as solvated electrons are
      discussed basing on the analysis of alkali metal NMR and ESR spectra.
      Surprisingly it seems that the stability of metal solutions in tetrahydrofuran at
      ambient temperature is inversely proportional to the durability of K+ complex in
      the case of five studied ligands. The most stable metal solutions were obtained
      using 15-crown-5. It was shown that the characteristic blue colour of metal
      solutions is not connected with the presence of solvated electrons but with metal
      anions.

PMID- 10888431
TI  - Fourier transform infrared spectra and normal mode analysis of 1-[(3
      methylphenyl)piperazin-1-yl]-3-[thio(4-acetamido-phenyl]pro pane: a potent 5-HT2
      and D2 receptor ligand.
AB  - 1-[(3-methylphenyl)piperazin-1-yl]-3-[thio(4-acetamidophenyl]propa ne and its
      analogs have shown good hypotensive activity and the title compound has shown a
      profile of centrally acting anti-hypertensive agent. It also binds with the 5-HT2
      receptors. The conformation of the title compound was determined by X-ray
      diffraction but this is not possible for its analogs because of the difficulty in
      preparing their single crystals. A novel and easy approach is envisaged to
      determine the conformation in such cases by the application of semi-empirical
      molecular orbital calculations, Fourier transform infra red (FTIR) spectroscopy
      and normal mode analysis. As a first step in this direction the FTIR spectrum of
      the title compound has been recorded and its normal mode analysis carried out.
      The assignments of the frequencies are based on the concept of group frequencies
      and band intensities. The spectrally observed frequencies have been tabulated
      along with the theoretically calculated ones and their assignments. Good
      agreement has been obtained between them and a set of 101 force field constants
      is established.

PMID- 10888432
TI  - Vibrational and 57Fe-Mossbauer spectra of FeTbGe2O7.
AB  - The infrared, Raman and 57Fe-Mossbauer spectra of FeTbGe2O7 were recorded and
      analyzed on the basis of its crystallographic data. For comparative purposes,
      similar measurements were also performed with FeYGe2O7 and with other
      isostructural compounds containing different lanthanide cations.

PMID- 10888433
TI  - Frequency of OH in solutions of n-butanol in carbon tetrachloride: effect of
      dilution.
AB  - It is noted that the 1 <-- 0 transition for nuOH shows a blue shift as the
      relative concentration of n-butanol in a CCl4-n-butanol is reduced. The magnitude
      of the shift decreases for the 2 <-- 0 transition and there is almost no shift
      for the 3 <-- 0 transition. These observations are consistent with the observed
      red shift [Y. Mizugai, F. Takimoto, M. Katayama, Chem. Phys. Lett. 76 (1980) 615]
      on dilution for the 5 <-- 0 transition in n-butanol. The observations have been
      interpreted on the basis of formation of O-H....Cl hydrogen bond.

PMID- 10888434
TI  - FT-IR spectroscopy of supersaturated aqueous solutions of magnesium borate.
AB  - FT-IR spectra of supersaturated aqueous solution of magnesium borate, its
      acidized solutions with azeotropic hydrochloric acid, and its diluted solutions
      with water have been recorded. The FT-IR spectra of borate in solution are
      obtained by difference, subtracting the FT-IR spectrum of water from that of the
      magnesium borate supersaturated aqueous solution. All of the results showed that
      various polyborate anions in the supersaturated aqueous solutions exist. The
      bands of symmetric pulse vibration of the corresponding polyborate anions were
      indicated and some assignments were tentatively given.

PMID- 10888435
TI  - Isotopic studies of the metal-ligand vibrations in histamine complexes with
      copper(II).
AB  - Two known copper complexes of the formulae Cu(hm)2(ClO4)2, Cu(hm)Cl2 and new,
      Cu(hm)Br2 (hm = histamine) have been investigated in the 600-50 cm(-1) far
      infrared region. Assignments of vibrations related to metal-ligand bonds have
      been made based on metal isotope substitution, partial deuteration and halogen
      sensitivity. Copper-hm stretching vibrations have been localised at 420, 417 and
      411 cm(-1) for modes involving amine nitrogen and at 282, 270, 259 cm(-1) for
      those of imidazole nitrogen. Vibrational coupling between some metal-ligand modes
      has been postulated.

PMID- 10888436
TI  - Vibrational study and spectra-structure correlations in ammonium saccharinate:
      comparison with the alkali saccharinates.
AB  - The FT IR spectra, at temperatures from liquid-nitrogen boiling (LNT) up to room
      temperature (RT), as well as the RT Raman solid-state spectra of protonated and
      deuterated ammonium saccharinate and of a series of alkali (Na, K, Rb, Cs)
      saccharinates are studied. The spectral assignments are aided with ab initio
      calculations on the free saccharinato anion at the HF/6-31 + + G(d,p) level.
      Attention is paid to the ND, CO and SO2 stretching regions. Correlation splitting
      is believed to be responsible for the presence of a v(CO) doublet. The averaged
      v(CO) frequency in (purely ionic) ammonium saccharinate is found to be the lowest
      in the so far studied saccharinates, along with the assumptions that the v(CO)
      frequency (or the corresponding averaged value) can have predictive value for the
      type of the metal-to-saccharinato ligand/ion bonding. The appreciably higher
      contribution of the dominating internal coordinate in the corresponding normal
      vibration in case of v(as)(SO2) than in v(s)(SO2) makes it suitable for spectra
      structure correlations. Contrary to RT, even though no phase transitions were
      observed in the studied temperature range, some polycentered character is
      prescribed to the hydrogen bonds in which the ammonium ions of effective symmetry
      C8 participate at LNT. Certain structural predictions about the saccharinates of
      K, Rb and Cs are made.

PMID- 10888437
TI  - The synthesis and application of 1-(o-nitrophenyl)-3-(2-thiazolyl)triazene for
      the determination of palladium(II) by the resonance enhanced Rayleigh light
      scattering technique.
AB  - The resonance Rayleigh light-scattering (RRLS) signal of a new triazene reagent;
      1-(o-nitrophenyl)-3-(2-thiazolyl)triazene (o-NPTT), was firstly synthesized and
      characterized in this paper at 500-600 nm wavelength range and can be enhanced
      remarkably by Pd2+. According to this phenomenon, a new method was developed for
      the determination of Pd2+ by the RRLS technique in the presence of Tween-80. The
      calibration graph showed good linearity over a concentration range of 5.0-700
      microg l(-1) with a detection limit of 1.0 microg l(-1). There are almost no
      foreign ions interfered in the determination at a more than fivefold
      concentration of Pd2+. The method is relatively sensitive, of good selectivity
      and has been successfully used for the determination of trace palladium in the
      slag of fertilizer factories and catalyst samples.

PMID- 10888438
TI  - The infrared fundamental intensities and polar tensor of CF4.
AB  - Atomic polar tensors of carbon tetrafluoride are calculated from experimental
      fundamental infrared intensities measured by several research groups. Quantum
      chemical calculations using a 6-311 + + G(3d, 3p) basis set at the Hartree-Fock,
      Moller-Plesset 2 and Density Functional Theory (B3LYP) levels are used to resolve
      the sign ambiguities of the dipole moment derivatives. The resulting carbon mean
      dipole moment derivative, pC = 2.051 e, is in excellent agreement with values
      estimated by a MP2/6-311 + + G(3d, 3p) theoretical calculation, 2.040 e, and by
      an empirical electronegativity model, 2.016 e. The pC value determined here is
      also in excellent agreement with the one obtained from the CF4 1s carbon
      ionization energy using a simple potential model, 2.059 e. Crawford's G intensity
      sum rule applied to the fundamental intensities of CH4, CH3F, CH2F2 and CHF3
      results in a prediction of a 1249 km mol(-1) intensity sum for CF4 in good
      agreement with the experimental values of 1328 +/- 37.9, 1208.0 +/- 54.4 and
      1194.8 +/- 7.4 km mol(-1) reported in the literature.

PMID- 10888439
TI  - Synergistic fluorescence enhancement of Tb with aromatic monocarboxylic acids and
      TOPO-Triton X-100: role of Triton X-100 in synergism.
AB  - Fluorescence enhancement of Tb3+ has been studied, using substituted benzoic
      acids as ligands. These ligands enhance the fluorescence of Tb3+ by about three
      orders of magnitude. The enhancement is observed due to ligand sensitized
      fluorescence. The fluorescence of Tb3+ in these complexes is synergistically
      enhanced by the addition of trioctylphosphine oxide (TOPO) in Triton X-100. The
      synergism displayed by TOPO was observed only when Triton X-100 micellar medium
      was used. TOPO dissolved in SDS/DTAB micellar medium did not result in
      synergistic fluorescence enhancement of Tb3+. These observations are discussed in
      detail and the synergism displayed by TOPO is rationalized on the basis of the
      structure of the surfactants.

PMID- 10888440
TI  - EPR and IR spectral studies of the sea water mussel Mytilus conradinus shells.
AB  - The electron paramagnetic resonance (EPR) and infrared (IR) spectral studies have
      been employed on the periostracum, the prismatic layer and the nacre of the shell
      of the marine bivalve molluscan Mytilus conradinus of the South Indian origin.
      All the layers of this shell show Fe3+ ion spin resonance signals in common. The
      inner layer namely nacre at room temperature shows EPR signals of Fe3+ ions and
      the heated one exhibits a sextet hyperfine pattern characteristic of Mn2+ ions.
      The prismatic layer of the shell also exhibits a similar spectrum, but of
      distinct pattern. The spin-Hamiltonian parameters have been evaluated for the
      prismatic and nacreous layers of this shell. Infrared spectra of the two main
      layers of the shell namely prismatic and the nacre exhibit the characteristic
      bands of CO3(2-) molecular ion in different symmetries of CaCO3.

PMID- 10888442
TI  - Diastereotopy in some 3,4-dihydroisocoumarins--effect of changing the
      substituents on the chiral centre.
AB  - Diastereotopy has been investigated in eight different derivatives of 3,4
      dihydroisocoumarins by changing the substituent on the pyran ring chiral centre,
      C-3. A diastereotopic NMR effect is observed for the prochiral methylene protons
      on the benzopyran ring and the effect is greatly influenced by the pi-electron
      system of the substituent. The effect is also observed for the substituents,
      however, the extent of diastereotopy depends upon their nature and the separation
      of methylene groups from the chiral centre.

PMID- 10888441
TI  - Electronic spectra of adenine and 2-aminopurine: an ab initio study of energy
      level diagrams of different tautomers in gas phase and aqueous solution.
AB  - Ground and lowest two singlet excited state geometries of four tautomeric forms
      (N9H, N7H, N3H and N1H) of each of adenine and 2-aminopurine (2AP) were optimized
      using an ab initio approach employing a mixed basis set (6-311 + G* on the
      nitrogen atom of the amino group and 4-31G basis set on the other atoms). Excited
      states were generated employing configuration interaction involving single
      electron excitations (CIS). Subsequently, the different species were solvated in
      water employing the self-consistent reaction field (SCRF) approach along with the
      corresponding gas phase optimized geometries. Thus the observed absorption and
      fluorescence spectra of adenine and 2AP have been explained successfully. It is
      concluded that both the N9H and N7H forms of 2AP would contribute to absorption
      and fluorescence spectra. Further, the fluorescence of 2AP would be absorbed by
      its cation in which both the N9 and N7 atoms are protonated, the fluorescence of
      which can have an anti-Stokes component. Among the different tautomers of
      adenine, the N9H form would be present dominantly in the ground state in aqueous
      solutions but the N7H form would be produced by energy transfer and subsequent
      fluorescence. The N3H form of adenine appears to be responsible for the observed
      absorption near 300 nm by its solutions intermittently exposed to ultraviolet
      radiation. The rings of the different species related to 2AP and adenine remain
      almost planar in the pi-pi* and n-pi* singlet excited states as in the ground
      state. The pyramidal character of the amino group is usually less in the pi-pi*
      excited states than that in the corresponding ground or n-pi* excited states.
      Molecular electrostatic potential (MEP) maps of the molecules provide useful
      clues regarding phototautomerism.

PMID- 10888443
TI  - Photophysical properties of sexi(3-methoxythiophene): evidence for energy
      migration in a conducting oligomer, based on fluorescence quenching.
AB  - The electronic absorption and fluorescence excitation and emission spectra of
      poly(3-methoxythiophene) (PMOT), a soluble, electroactive oligomer mainly
      constituted of hexamer, were investigated in dimethylsulfoxide at room
      temperature. The study of PMOT photophysical properties suggests the existence of
      important pi-electronic delocalization in the oxidized and reduced form of the
      oligomer. A significant fluorescence quenching of PMOT takes place in the
      presence of various quenchers such as dimethylterephthalate, potassium iodide and
      thallium acetate. Quenching mechanisms implying a quencher-induced intersystem
      crossing step are proposed. Modified Stern-Volmer relationships were obtained
      with large quenching bimolecular rate constants (2.7 x 10(9)-6.1 x 10(11) l mol(
      1) s(-1)), which suggests electronic energy migration throughout the repeat units
      of the PMOT hexamer.

PMID- 10888444
TI  - Spectral behavior and pH dependence of N-hexadecyl-5-iminomethyl-8
      hydroxyquinoline.
AB  - A new kind of amphiphile derived from 8-hydroxyquinoline, N-hexadecyl-5
      iminomethyl-8-hydroxyquinoline (HIHQ) was synthesized and characterized by
      different physical methods. The influence of pH value on UV-vis absorption,
      fluorescence spectra were investigated and the surface pressure area isotherms
      were recorded under different pH subphase. The linear response range between the
      emission intensity and the concentration of HIHQ was 1-4 x 10(-6) mol L(-1). The
      strongest emission of HIHQ about 460 nm was obtained at pH 8.2 and the acid-base
      equilibrium of HIHQ in monolayer and solution was also discussed.

PMID- 10888445
TI  - The evaluation of structural changes in wool fibre keratin treated with azo dyes
      by Fourier Transform Infrared Spectroscopy.
AB  - Fourier Transform Infrared Spectroscopy spectroscopy is a useful technique for
      the analysis of structural changes in wool fibres at the molecular and
      supermolecular levels. Ecological requirements the textile industry has to meet
      oblige manufacturers to use ecological dyes in the process of fibre dyeing. These
      dyes should not split into the forbidden, carcinogenic aromatic amines (e.g.
      benzidine) while used. Wool was dyed with an azo dye, then underwent a chemical
      reaction. Changes were observed in the region of Amide A, Amide B, Amide I and
      II, dipolar ions amino acids, and the fingerprint region.

PMID- 10888446
TI  - Electronic excitation as a mechanism of the ion selectivity filter.
AB  - A correlation between the character of pharmacological activity and the energies
      of electronic transitions in some biologically active molecules, affecting the
      nervous system, has been found. In order to explain the correlation, a new
      principle of the membrane ion selectivity filter has been suggested. The
      principle is based on the recombination process of a metal cation, passing
      through the filter, with an electron, when the energy quantum (equal to the metal
      ionization energy) is emitted. The amino acid residue group, performing the
      function of the channel filter, absorbs this quantum, transits itself into an
      electronically excited state, changes its conformation and lets, as a result, the
      cation pass. The process is possible only in that case when the amino acid
      residue group has a transition of the same energy, therefore not all of metals
      can pass through the filter. From the viewpoint of this conception, an active
      molecule acts because of its transition into an electronically excited state of
      the same energy and interfering, thereby, with the natural processes.

PMID- 10888447
TI  - Characterization of the fluorescence emission properties of prodan in different
      reverse micellar environments.
AB  - We have examined the steady state and time resolved fluorescence emission
      properties of the hydrophobic fluorescence probe, prodan, in three representative
      reverse micellar systems formed by the surfactants poly(oxyethylene)
      (tetramethylbutyl) phenylether (Triton X-100, neutral), cetyl trimethylammonium
      bromide (CTAB, cationic) and sodium bis-(2-ethylhexyl) sulfosuccinate (AOT,
      anionic) in organic solvent media containing different concentrations of water.
      The results obtained from the experiments indicate conspicuous dependence of the
      emission behaviour of prodan on the type of surfactant used and the
      water/surfactant molar ratio (w0). The nature of the emission profiles, along
      with relevant parameters namely emission maximum (lambda(em)max), anisotropy (r)
      and lifetime (tau) data are used to infer the distribution and microenvironments
      of the prodan molecules in the reverse micelles at different w0 values.
      Furthermore, quantitative estimates have been obtained for the polarities (in
      terms of the empirical polarity parameter E(T)(30)) of the sites of
      solubilization of the fluorophore in different reverse micellar systems.

PMID- 10888448
TI  - Early neonatal presentations to the pediatric emergency department.
AB  - As a result of shorter postpartum hospital stays, many medical concerns, which
      traditionally have been managed in newborn nurseries, are presenting to the
      pediatric emergency department (PED). We undertook a study to determine the
      profile of early neonatal visits to the PED. In addition, we examined the
      influence of maternal factors and length of postpartum hospital stay on PED
      visits. METHODS: We conducted a retrospective chart review of all neonates < or =
      8 days of age who presented to the PED between June 1990 and May 1995. Data
      gathered from neonatal and corresponding maternal charts included neonatal and
      maternal demographics, prenatal instruction, length of postpartum stay, source of
      referral, age at presentation, presenting complaint, diagnosis, disposition, and
      course in hospital, if admitted. RESULTS: A total of 559 neonatal visits were
      identified. Neonatal use of the PED increased 245% compared to an overall
      increase in PED use of 8.7% during the study period. Jaundice, difficulty
      breathing, feeding problems, and irritability were the most common presenting
      complaints while the most frequent diagnoses were normal physiology, jaundice,
      feeding problems, and query sepsis. Our overall admission rate was 33%. Self
      referred patients were at a significantly lower risk of serious illness (16%
      admitted vs 49 % of consult patients). The self-referral rate increased with
      maternal age less than 21, single marital status, no prenatal classes, and
      primiparity. The length of postpartum hospital stay was identified in 389
      neonates (55 early discharge (ED) and 334 non-early discharge (NED). The ED group
      had a significant increase in annual PED utilization compared to the NED group
      changing from 2% of the total population in study year 1 to over 31% in the final
      year. The ED and NED groups did not differ significantly with respect to the
      majority of chief complaints, frequency of PED diagnoses, admission rates, or
      maternal characteristics. CONCLUSIONS: Use of the PED by neonates < or = 8 days
      of age increased significantly over the study period. The majority of neonates
      presented by self-referral and were discharged with advice only. Mothers who were
      young, single, primiparous, or who had not attended prenatal classes presented
      with neonates who were less seriously ill. Although ED neonates represent an
      enlarging subset of PED visitors, they do not appear to differ significantly from
      NED neonates with respect to PED complaints, diagnoses, and disposition.

PMID- 10888449
TI  - Characteristics and outcome of children with carbon monoxide poisoning with and
      without smoke exposure referred for hyperbaric oxygen therapy.
AB  - OBJECTIVES: To describe the clinical characteristics and outcome of children with
      carbon monoxide (CO) poisoning with and without smoke exposure referred for
      hyperbaric oxygen therapy (HBOT), and to determine the association between any of
      these characteristics and death. SETTING: Regional hyperbaric referral center.
      PATIENTS: The medical records of 150 children with CO poisoning (COP) who were
      treated with HBOT between August 92 and September 95 were reviewed.
      MEASUREMENTS/MAIN RESULTS: COP was defined as a history of probable exposure to
      CO, with either a carboxyhemoglobin level (COHb) > 25, or COHb < 25 with
      neurological, respiratory, or cardiac compromise. Major cutaneous burns were
      described as second degree burns over greater than 20% of the patient's total
      body surface area (TBSA), or third degree burns over greater than 10% of the
      patient's TBSA. Children extracted from a closed-space fire who had airway soot,
      singed facial hair/facial burns, or respiratory distress were defined as having
      smoke inhalation and carbon monoxide poisoning (CO/SI). CO/SI occurred in 40.1%
      of patients. Compared to children with COP alone, those with CO/SI were
      significantly more likely to have a depressed mental status upon arrival to an ED
      (76.3 % vs 13.6 %, P < 0.001), lower mean initial GCS (6.7 vs 14.7, P < 0.001),
      lower mean initial pH (7.2 vs 7.4, P < 0.001), respiratory arrest at the scene
      (68.5% vs 0%, P < 0.001), and cardiac arrest at the scene (25.9% vs 0%, P <
      0.001). Children with CO/SI were significantly more likely to have a poor outcome
      (death) than children with COP alone (22.6% vs. 0%, P < 0.001). Comparing
      children with CO/SI who died versus survivors, there were significant differences
      in mean initial COHb (38.3 vs 24.3, P = 0.03), mean initial temperature upon
      arrival in an ED (94.9 degrees F vs 98.2 degrees, P < 0.006), respiratory arrest
      at the scene (92% vs 59.6%, P = 0.04), and cardiac arrest at the scene (66.7% vs
      13.5%, P < 0.001). Sixty percent of children died who had a combination of risk
      factors of smoke inhalation, low temperature, high COHb level, and respiratory
      and cardiac arrest in the field. CONCLUSIONS: These preliminary data suggest that
      children with COP alone who are treated with HBOT are at low risk for dying
      regardless of initial COHb level. Children with CO/SI have a significantly higher
      risk of dying than those children with COP alone. A combination of smoke
      inhalation, low temperature, high COHb level, respiratory arrest, and cardiac
      arrest is highly associated with death. Prospective studies are needed to confirm
      and further define these associations.

PMID- 10888450
TI  - Prenatal care and infant emergency department use.
AB  - OBJECTIVE: To determine the relationship between mothers' use of prenatal care
      and pediatric emergency department (ED) use by their infants in the first 3
      months of life. METHODS: This is a retrospective, cohort-control study of well,
      full-term infants who use a children's hospital ED. Using logistic regression,
      the likelihood of an emergency visit in the first 3 months of life was compared
      between infants of women with fewer than two prenatal visits and infants of women
      with two or more prenatal visits. Covariates were maternal age, race, substance
      abuse history, parity, infant birth weight, insurance status, and distance from
      the ED. RESULTS: The odds of an ED visit before age 3 months by infants of
      mothers with less than two prenatal visits was 29% lower than the comparison
      group. ED use was increased by proximity, Medicaid or no health insurance and
      younger maternal age. Seventy percent (70%) of visits by both cohorts were
      classified as unjustified. The odds of making an unjustified ED visit were
      increased by younger maternal age and proximity to the emergency department.
      CONCLUSIONS: Women with poor prenatal care are less likely to seek ED care for
      their young infants. Although suboptimal prenatal care is associated with
      negative health outcomes, it is not known whether fewer infant ED visits are
      similarly deleterious.

PMID- 10888451
TI  - Appendicitis in the young child: a continuing diagnostic challenge.
AB  - OBJECTIVE: The purpose of this review was to examine the presenting signs and
      symptoms of children 5 years of age or less who underwent operation for
      appendicitis. In addition, we sought to determine the rate of perforation of the
      appendix and the effect on outcome in this age group. METHODS: Medical records
      for the period September 1987 to September 1998 were reviewed for all children 5
      years of age or less who underwent appendectomy for appendicitis. Data gathered
      included age at operation, gender, care sought prior to admission for
      appendectomy, duration of symptoms, signs and symptoms at the time of admission,
      and length of postoperative hospital stay. Symptoms of diarrhea, emesis, fever,
      pain, and anorexia were recorded. Physical signs of an abdominal mass, guarding,
      rebound tenderness, rigidity, and diffuse or focal tenderness were recorded.
      Diagnostic information included white blood cell count with differential, and
      radiographic imaging, if obtained. The presence or absence of perforation of the
      appendix, and abscess formation were based on the intraoperative impression of
      the operating surgeon. RESULTS: For the 11-year period, 120 patients 5 years of
      age or less required an operation for appendicitis and had a complete medical
      database. The mean age was 3.6 +/- 1.3 years; 53% were male. Patients underwent a
      separate medical evaluation prior to arriving at a definitive diagnosis in 44.2 %
      cases. The most common presenting symptom was abdominal pain (94%); the most
      common sign was abdominal tenderness (95.8%). Tenderness was generally diffuse if
      perforation had occurred (62%) or focal in the nonperforated group (61%). The
      duration of symptoms in patients with perforation was more than double that of
      the nonperforated patients (4.7 vs 2.1 days, respectively). The mean white blood
      cell count (WBC) was 18.3 +/- 7.4 cells/mm3, and did not differ significantly
      between the perforated and nonperforated groups. A left shift detected in the WBC
      differential was present in 91%. An abdominal radiograph was obtained in 87%, and
      demonstrated a fecalith in 18%. A preoperative ultrasound was obtained in 38%, a
      computed tomographic scan in 7%. At the time of surgery, 74% were found to have
      evidence of perforation. An abscess was found at the initial surgery in 47% of
      patients with appendiceal perforation, but in no patient in whom perforation had
      not occurred. The rate of perforation increased as the age of the patient
      decreased (100% perforation for age 1 (n = 10) to 69% for age 5, (n = 35).
      Perforation was associated with a longer hospital length of stay as compared to
      the nonperforated appendix (median 9 days vs. 3 days, respectively, P < 0.001).
      There were no deaths in this series. CONCLUSION: Appendiceal perforation
      continues to be a common occurrence in the young child and increases in frequency
      as the age of the patient decreases and the duration of symptoms lengthens.
      Perforation results in a significant increase in hospital length of stay and rate
      of abscess formation.

PMID- 10888452
TI  - Metal detectors in the pediatric emergency department: patron attitudes and
      national prevalence.
AB  - OBJECTIVES: The purpose of this study was to investigate patron attitudes toward
      a walk through a metal detector that was used for universal weapon screening in a
      pediatric emergency department. Additionally, we conducted a telephone survey to
      determine the nationwide prevalence of metal detectors in pediatric emergency
      departments. METHODS: A convenience sample of family and acquaintances of
      patients seen in the pediatric emergency department was selected, and members
      were interviewed using scripted questions. Members of the National Association of
      Children's Hospitals and Related Institutions were interviewed for the nationwide
      survey. RESULTS: The vast majority of patrons responded favorably to the presence
      of the arch-style walk through a metal detector. The metal detector was felt to
      be appropriate in a pediatric emergency department by a large majority of patrons
      and was protective for both patrons and employees. Handbag searches were felt to
      be an invasion of privacy by 14%. Nationwide, the prevalence of arch-style metal
      detectors for security purposes in pediatric emergency departments was only 6%.
      CONCLUSIONS: The public has a strong perception that a metal detector protects
      both patrons and employees in a pediatric emergency department. Fear that patrons
      will be disturbed or that the presence of a metal detector will reflect
      negatively upon the institution appear to be unfounded. Nationwide use of metal
      detectors in pediatric emergency departments remains uncommon but is apparently
      increasing.

PMID- 10888453
TI  - Resident training in pediatric critical care transport medicine: a survey of
      pediatric residency programs.
AB  - OBJECTIVE: The Accreditation Council for Graduate Medical Education (ACGME)
      Program Requirement for Pediatrics includes specific objectives that pediatric
      residents participate in both the pre-hospital care of acutely ill or injured
      patients and the stabilization and transport of patients to critical care areas.
      Previously, residents were often included as the physician component for many
      pediatric critical care transport teams. Subsequent regionalization of transport
      services and development of nurse-only transport teams prompted us to determine
      the current level of resident participation in pediatric critical care transport
      as well as how individual residency programs were meeting the educational
      objectives. METHODS: A questionnaire was mailed to each pediatric residency
      program listed in the 1996-1997 GME Directory. Information was obtained regarding
      the size of the hospital and the residency program, the presence of a pediatric
      critical care transport team, the number of annual transports, and transport team
      leader. In addition, the use of pediatric residents for transports was
      ascertained, as well as their specific role, training requirements, and method of
      evaluation. RESULTS: Data were received from 138 programs for a return rate of
      65%. Eighty percent of programs offered a pediatric critical care transport
      service. Nurse-led teams were used for 51% of NICU and 44% of PICU transports. Of
      the 82 NICU and 84 PICU teams that used residents, the majority used them as team
      leaders (60% and 70%; respectively) with only the minority requiring that they be
      at the PL-3 year or greater. The training and/or certification required for
      resident participation in transports varied among programs, with 85% requiring
      completion of a NICU or PICU rotation, and 94% requiring NRP or PALS
      certification. Programs that did not allow resident participation provided
      exposure to Transport Medicine by various mechanisms, including lectures and
      emergency department (ED) rotations. CONCLUSION: Pediatric resident participation
      in critical care transport varies widely among pediatric critical care transport
      teams. The degree to which residents participate in the transport team would
      appear to have diminished in comparison to previous studies. Transport teams
      often use other resources, such as nurses, fellows, or attendings, to lead their
      transport teams. Pediatric resident exposure to and participation in Transport
      Medicine varies among programs, as do the methods used to prepare residents for
      their experience.

PMID- 10888454
TI  - Ovarian small cell carcinoma: a rare neoplasm in a 15-year-old female.
AB  - Abdominal masses in children are uncommon. Ovarian neoplasms are uncommon in
      young children and adolescents, and typically are benign. Small cell carcinoma of
      the ovary is an extremely rare condition, with a very poor prognosis. We report
      the case of a 15-year-old female who presented to the emergency department with
      abdominal distention, abnormal vaginal bleeding, and constipation secondary to a
      large intra-abdominal mass, ultimately diagnosed as ovarian small cell carcinoma.

PMID- 10888455
TI  - Diaper burn: accident, abuse, or neglect.
AB  - A 7-year-old, female with mental retardation and seizure disorder was admitted
      with burns. Reportedly, her brother who was 12 years old was cooking dinner for
      himself. A towel caught fire. He threw the towel over his head, and the patient's
      diaper ignited. She had partial thickness second-degree burns over her right
      elbow, upper abdomen, both inner thighs, and buttocks with multiple blistering,
      which was estimated to be 7% of the total body surface. The child abuse team took
      a diaper similar to the one the child was wearing at the time of injury and found
      that it easily ignited and melted in several seconds. This is the first medically
      reported burn case due to a disposable diaper.

PMID- 10888456
TI  - Abdominal compartment syndrome in a patient with congenital megacolon.
AB  - A 13-year-old male with a history of chronic congenital megacolon presented to
      the emergency department with a 1-day history of increasing abdominal pain,
      distension, and emesis. The patient was admitted for bowel disimpaction and
      irrigation. The patient rapidly developed an acute abdominal compartment syndrome
      because of his massive colonic dilation. Surgical decompression resulted in a
      reperfusion phenomenon and ultimately resulted in coagulopathy and patient
      demise. This case presents a unique cause of the abdominal compartment syndrome
      and discusses the implications to the emergency physician.

PMID- 10888457
TI  - Inguinoscrotal bruising: a sign of neonatal adrenal hemorrhage.
AB  - A 5-day-old baby presented with right inguinoscrotal bruising. The underlying
      testis and cord were normal on examination. Intra-abdominal bleeding was
      suspected. Abdominal ultrasound showed right adrenal hemorrhage. This was managed
      nonoperatively and with supportive therapy; the inguinoscrotal bruising resolved
      spontaneously.

PMID- 10888459
TI  - Plantar hidradenitis in children induced by exposure to wet footwear.
AB  - Painful erythematous papules and nodules involving either the palms of the hands,
      or, more commonly, the soles of the feet, characterize palmoplantar eccrine
      hidradenitis or palmoplantar hidradenitis (PH). The younger pediatric population
      is predominately affected. Histologically, the eccrine gland apparatus is the
      target of inflammatory neutrophilic infiltrates. This entity has been reported
      under a variety of names, including traumatic plantar urticaria, neutrophilic
      eccrine hidradenitis, plantar erythema nodosum, and idiopathic recurrent
      palmoplantar hidradenitis. All are essentially the same process, described in
      different forms. Despite the growing number of reported cases, the pathogenesis
      remains obscure. We present four children with PH of the soles of the feet, who
      shared a common recent history of exposure to cold, damp, footwear. The temporal
      relationship between exposure to dampness and cold and the appearance of the skin
      lesions suggest a possible pathogenetic mechanism.

PMID- 10888458
TI  - Traumatic avulsion of kidney into the chest through a ruptured diaphragm in a
      boy.
AB  - This report presents a case of a teenage patient who survived following severe
      blunt trauma with complete avulsion of the right kidney into the chest through a
      ruptured diaphragm. The combination of kidney avulsion into the chest is
      extremely rare. Only three similar cases have been reported in the English
      literature to date (1-3).

PMID- 10888460
TI  - Recognizing vertebral artery dissection in children: a case report.
AB  - Vertebral artery dissection is an unusual cause of stroke especially in children.
      The majority of dissections are thought to be caused by trauma although in many
      cases the trauma may be trivial. In other cases, certain underlying pathological
      processes are thought to be risk factors. We report a case of vertebral artery
      dissection in a 9-year-old child who presented with neurologic deficits
      suggestive of a posterior circulation stroke. The signs and symptoms of this
      unusual entity can be subtle and intermittent over a period of days to weeks;
      thus, making it very difficult to recognize. Therefore, it is important to
      consider the possibility of vertebral artery dissection in the differential
      diagnosis of neurologic deficits in children.

PMID- 10888461
TI  - Abdominal trauma in infants and children: prompt identification and early
      management of serious and life-threatening injuries. Part II: Specific injuries
      and ED management.
AB  - Evaluation of children with suspected abdominal trauma could be a difficult task.
      Unique anatomic and physiologic features render vital sign assessment and the
      physical examination less useful than in the adult population. Awareness of
      injury patterns and associations will improve the early diagnosis of abdominal
      trauma. Clinicians must have a complete understanding of common and atypical
      presentations of children with significant abdominal injuries. Knowledge of the
      utility and limitations of available laboratory and radiologic adjuncts will
      assist in accurately identifying abdominal injury. While other obvious injuries
      (eg, facial, cranial, and extremity trauma) can distract physicians from less
      obvious abdominal trauma, an algorithmic approach to evaluating and managing
      children with multisystem trauma will improve overall care and help to identify
      and treat abdominal injuries in a timely fashion. Finally, physicians must be
      aware of the capabilities of their own facility to handle pediatric trauma.
      Protocols must be in place for expediting the transfer of children who require a
      higher level of care. Knowledge of each of these areas will help to improve the
      overall care and outcome of children with abdominal trauma.

PMID- 10888462
TI  - Emergency department management of pediatric migraine.
AB  - Migraine is a common pediatric emergency department problem. Since its
      pathophysiology is unclear and possibly multifactorial, a single treatment
      strategy is unlikely to be successful for all patients. A specific treatment that
      has been successful for a particular patient should be strongly considered.
      Otherwise, it is best to start with simple therapies such as acetaminophen,
      aspirin, or an NSAID if not already tried at home. For patients requiring more
      specific therapy, reasonable choices would be dihydroergotamine or a dopamine
      antagonist such as prochlorperazine. There are several newer agents studied in
      adults with examples being sumatriptan and naratriptan. These probably have a
      role in the adolescent and should be considered in the younger age group when
      other therapies have failed. When the headache has been prolonged, dexamethasone
      may be useful in decreasing inflammation and relieving pain. As illustrated in
      many of the above studies, monotherapy is often inadequate in achieving complete
      relief of headache pain in all patients. Most of the drugs discussed here address
      only one of the three etiologies thought to be involved in migraine pathogenesis,
      namely; the dopaminergic system. the serotonin system or inflammation.
      Presumably, therapy directed toward more than one of these etiologies at the same
      time may be more effective (11).

PMID- 10888463
TI  - Pediatric emergency medicine: legal briefs.

PMID- 10888464
TI  - To go by the books.

PMID- 10888465
TI  - I stepped in a hole and can't walk.

PMID- 10888466
TI  - Sports-specific concerns in the young athlete: baseball.
AB  - The sport of baseball is played by millions of children across America and around
      the world. Although generally considered a safe activity, it is estimated that
      there are over 100,000 acute baseball injuries yearly in the 5- to 14-year age
      range in the United States, many of which present to the emergency department.
      Acute injuries often involve ball impact to the face and hands; baseball is the
      leading cause of sport-related eye injury. Ball impact particularly to the chest
      results in a small but steady number of fatalities each year, many of which are
      widely publicized events. In addition to acute injury, many young baseball
      players are affected by chronic and acute conditions of the elbow. In this
      article, we review the history, epidemiology, and common injury patterns that are
      specific to baseball. Case reports are included, as well as a section on the
      physical examination of the elbow.

PMID- 10888467
TI  - Hematuria as a complication of sudden decompression of chronically distended
      bladder in a child with neurogenic bladder dysfunction.

PMID- 10888468
TI  - Nitric oxide: a unique endogenous signaling molecule in vascular biology.
AB  - The properties of nitric oxide as an endogenous cell signaling molecule in
      vascular biology are described.

PMID- 10888469
TI  - The histidine decarboxylase (HDC) gene of Tetrahymena pyriformis is similar to
      the mammalian one. A study of HDC expression.
AB  - RNA was isolated from Tetrahymena pyriformis GL and using human histidine
      decarboxylase (HDC) gene primers, the RT-PCR product was sequenced. A fraction
      containing 207 base pairs was compared to the published sequences of prokaryotic
      and mammalian (rat, mouse and human) HDC cDNA (exons). The HDC-cDNA fraction of
      Tetrahymena was similar to the mammalian cDNA-s and it was completely different
      from the prokaryotic HDC-gene. The results indicate the presence of a mammalian
      like HDC-gene already in a unicellular eukaryote organism and demonstrates also
      that the divergence of the prokaryotic-eukaryotic common gene took place already
      at this low evolutionary level.

PMID- 10888470
TI  - Fluorimetric analysis of phospholipase activity in Tetrahymena pyriformis GL.
AB  - The unicellular Tetrahymena enzymatically split the synthetic phosphodiester, 4
      methylumbelliferyl phosphocholine substrate. The enzyme activity was completely
      blocked in vitro and drastically inhibited in vivo by G-protein activating
      fluorides (NaF; AIF4- and BeF3-). The phospholipase A2 inhibitor, quinacrine, and
      the protein phosphatase inhibitor, neomycin, inhibited the enzyme activity in
      vitro and activated it in vivo. Another phospholipase A2 inhibitor 4-bromo
      phenacyl bromide was ineffective in vivo and in vitro alike, as well as the
      cyclooxygenase inhibitor indomethacin. Results of these experiments indicate that
      some treatments could be specific for a well defined activity (e.g.,
      phospholipase A2, G-protein) but subject to influence by other enzymes (e.g.,
      phospholipase C, sphingomyelinase). The experiments call attention to the
      differences in the results of the in vivo and in vitro studies.

PMID- 10888471
TI  - Mitochondria present in excised patches from pancreatic B-cells may form
      microcompartments with ATP-dependent potassium channels.
AB  - Experiments with inside-out patches excised from pancreatic B-cells have yielded
      evidence that mitochondria are often contained in the cytoplasmic plug protruding
      into the tip of patch pipette. When intact B-cells were loaded with the
      fluorescent mitochondrial stain, rhodamine 123, and membrane patches excised from
      these cells, a green fluorescence could be observed in the lumen at the tip of
      the patch pipette. The same result was obtained with the mitochondrial stain,
      MitoTracker Green FM, which is only fluorescent in a membrane-bound state.
      Furthermore, the open probability of ATP-dependent potassium (K(ATP)) channels in
      inside-out patches was influenced by mitochondrial fuels and inhibitors.
      Respiratory substrates like tetramethyl phenylene diamine (2 mM) plus ascorbate
      (5 mM) or alpha-ketoisocaproic acid (10 mM) reduced the open probability of
      K(ATP) channels in inside-out patches significantly (down to 57% or 65% of
      control, respectively). This effect was antagonized by the inhibitor of
      cytochrome oxidase, sodium azide (5 mM). Likewise, the inhibitor of succinate
      dehydrogenase, malonate (5 mM), increased the open probability of K(ATP) channels
      in the presence of succinate (1 mM). However, oligomycin in combination with
      antimycin and rotenone did not increase open probability. Although it cannot be
      excluded that these effects result from a direct interaction with the K(ATP)
      channels, the presence of mitochondria in the close vicinity permits the
      hypothesis that changes in mitochondrial metabolism are involved, mitochondria
      and K(ATP) channels thus forming functional microcompartments.

PMID- 10888472
TI  - Inhibition of both Na/H and bicarbonate-dependent exchange is required to prevent
      recovery of intracellular pH in single cardiomyocytes exposed to metabolic
      stress.
AB  - Although tight regulation of intracellular pH (pHi) is critical for the survival
      under stress, paradoxically a slowed recovery of pHi under hypoxic injury may be
      cardioprotective. In this study, we investigated the recovery of pHi after
      hypoxia-induced intracellular acidosis in cardiomyocytes loaded with the H+
      sensitive dye SNARF-1. Exposure of single cardiomyocytes to 2,4-dinitrophenol
      (DNP), an inhibitor of mitochondrial oxidative phosphorylation, induced
      significant intracellular acidification. However, within 10-12 min upon removal
      of DNP, cardiomyocytes restituted their intracellular H+ concentration. The
      presence either of 5-N-ethyl-N-isopropylamiloride (EIPA) an inhibitor of Na/H
      antiporter, or 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), an
      inhibitor of bicarbonate-dependent exchange, did not modify the cellular response
      to DNP. But, combined use of EIPA and DIDS prevented the restitution of
      intracellular pH following removal of DNP. This study, thus, demonstrated, for
      the first time, that blockade of both Na/H and bicarbonate-dependent exchange is
      necessary and sufficient to maintain the hypoxia-induced intracellular
      acidification. Therefore, concomitant blockade of both pH-regulating mechanisms
      deserves to be further considered as a novel strategy against hypoxia
      reoxygenation injury in the heart.

PMID- 10888473
TI  - Phosphorylation of H,K-ATPase alpha-subunit in microsomes from rabbit gastric
      mucosa by cAMP-dependent protein kinase.
AB  - A 100-kDa protein that is a main component of the microsomal fraction from rabbit
      gastric mucosa is phosphorylated by cAMP-dependent protein kinase (PKA) in the
      presence of 0.2% Triton X-100. Microsomes from rabbit gastric mucosa possess
      activity of H,K-ATPase but not activity of Na,K-ATPase. Incubation of microsomes
      with 5 microM fluorescein 5'-isothiocyanate (FITC) results in both an inhibition
      of H,K-ATPase and labeling of a protein with an electrophoretic mobility
      corresponding to the mobility of the protein phosphorylated by PKA. The data
      suggest that the alpha-subunit of H,K-ATPase can be a potential target for PKA
      phosphorylation.

PMID- 10888474
TI  - One step isolation of bovine asialoglycoprotein receptor and its characterization
      by sequence analysis and MALDI mass spectrometry.
AB  - The asialoglycoprotein receptor (ASGP-R), which is responsible for the uptake of
      partially deglycosylated serum glycoproteins was isolated from bovine liver. The
      receptor was purified in one step from solubilized plasma membranes by affinity
      chromatography on 6-(beta-D-lactosyl)-n-hexylamine coupled to N
      hydroxysuccinimide activated Sepharose with a coupling degree of 7.6 micromol/ml
      gel. The preparation yielded two distinct polypeptides with apparent molecular
      weights of 48 and 43 kDa as determined by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis. A polyclonal antibody raised against the human ASGP-R
      recognized the bovine 43 kDa protein in Western blot analysis. The 48 and 43 kDa
      polypeptides were digested by trypsin and the digests were subsequently analyzed
      by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry. Sequence analysis of four tryptic fragments, two each of the 48 kDa
      and of the 43 kDa polypeptides revealed that these were highly homologous to ASGP
      R subunits from man, mouse and rat.

PMID- 10888475
TI  - Glycotargeting: influence of the sugar moiety on both the uptake and the
      intracellular trafficking of nucleic acid carried by glycosylated polymers.
AB  - Nucleic acids (plasmids as well as oligonucleotides) used to specifically express
      or modulate the expression of a gene, must reach the cytosol and/or the nucleus.
      Several systems have been developed to increase their uptake and their
      efficiency. Glycosylated polylysines have been shown to specifically help nucleic
      acids to be taken up in cells expressing a given cell surface membrane lectin.
      However, it appeared that the efficiency of the imported nucleic acid was not
      directly related to the extent of the uptake. Indeed, some glycosylated
      polylysines bearing sugar moities which are poor ligands of the cell surface
      lectins of a given cell were found to be more efficient than those bearing better
      sugar ligands. The interpretation of this paradoxal result is discussed with
      regards to the nature of the compartment allowing the nucleic acid to cross the
      membrane and to be delivered in the cytosol on the one hand, and to the presence
      of intracellular lectins on the other hand.

PMID- 10888476
TI  - Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective
      disorder.
AB  - Seasonal Affective Disorder (SAD) is prevalent when vitamin D stores are
      typically low. Broad-spectrum light therapy includes wavelengths between 280-320
      nm which allow the skin to produce vitamin D. This study was designed to test the
      hypothesis that vitamin D deficiency might play a role in SAD. A prospective,
      randomized controlled trial was conducted in a group of 15 subjects with SAD.
      Eight subjects received 100,000 I.U. of vitamin D and seven subjects received
      phototherapy. At the onset of treatment and after 1 month of therapy subjects
      were administered the Hamilton Depression scale, the SIGH-SAD, and the SAD-8
      depression scale. All subjects also had serum levels of 25-hydroxyvitamin D (25
      OH D) measured before and 1 week after intervention therapy. All subjects
      receiving vitamin D improved in all outcome measures. The phototherapy group
      showed no significant change in depression scale measures. Vitamin D status
      improved in both groups (74% vitamin D group, p < 0.005 and 36% phototherapy
      group, p < 0.01). Improvement in 25-OH D was significantly associated with
      improvement in depression scale scores (r2=0.26; p=0.05). Vitamin D may be an
      important treatment for SAD. Further studies will be necessary to confirm these
      findings.

PMID- 10888477
TI  - Does dietary iron intake influence the iron status in hospitalised elderly
      patients?
AB  - PURPOSE: To investigate whether there is a relationship between dietary iron
      intake and body iron store in hospitalised elderly. METHODS: During a three
      months period, 163 consecutive patients older than 70 years and irrespective of
      their medical diagnosis participated in this study. Eight patients were excluded
      because of a lack of co-operation or a too bad general condition. Total food
      intake data were collected at admission by using a 7 days food-intake and
      nutrient-supplement record. The average daily dietary intake of each of the
      nutrients (total energy intake and potential inhibiting or enhancing factors such
      as calcium, dietary fibres and vitamin C) were calculated. Serum levels of
      ferritin, iron, transferrin, haemoglobin and mean corpuscular volume were also
      measured in the 155 study patients. RESULTS: A depleted iron store, defined as a
      serum ferritin level < 50 microg/L, was found in 23 patients (15%) of whom 17
      were anaemic. The mean daily intake of iron (9.5 mg for the total group, 10 mg
      and 9.2 mg for men and women, respectively), vitamin C, calcium an dietary fibre
      was not significantly different between patients with depleted and adequate iron
      stores. The serum iron, transferrin, MCV, haemoglobin and ferritin levels were
      comparable between patients with a low (< 9 mg, n = 64) and normal (> or = 9 mg,
      n = 91) iron intake. We found no correlation between the dietary iron intake and
      the serum ferritin level (r = 0.06, p = 0.45), even not after exclusion of the
      patients with a serum ferritin level > 300 microg/L (r = 0.005, p = 0.95).
      CONCLUSION: We found no relationship between the dietary iron intake and
      biochemical indicators of the iron status in an elderly population. If no
      gastrointestinal or another organ-related cause might be found, iron deficiency
      can hardly be attributed to an impaired iron intake without a nutritional
      investigation. Other parameters may also play an important role in its
      multifactorial pathogenesis.

PMID- 10888478
TI  - CEBQ: Composite Eating Behavior Questionnaire--development and performance.
AB  - Poor eating behavior is an important nutritional risk factor among community
      dwelling elders, and precedes overt malnutrition in the majority of cases.
      Several tools were developed to assess nutritional risk through evaluating eating
      behavior. All containing elements shown to be related to nutritional decline.
      Given the diversity of the geriatric population each tool may apply to specific
      subsets of the population but not to all. The ideal tool may be a questionnaire
      tailored for the study population based on a pool of methods and questions. We
      describe the development and use of such a composite tool, and compares its
      performance to other questionnaires. Our results show that in community dwelling
      elders nutrition risk assessments such as the NRI or eating behavior score were
      not predictive of nutritional status measured by dietary intake, weight change or
      BMI. Subjective appetite assessment was the most predictive question for
      nutritional decline. We describe the questionnaire and its development and offer
      general advice to its future implementations.

PMID- 10888479
TI  - Modulation of renal xanthine oxidoreductase in aging: gene expression and
      reactive oxygen species generation.
AB  - Xanthine oxidoreductase (XD: xanthine dehydrogenase + xanthine oxidase) is a
      complex enzyme that catalyzes oxidation of hypoxathine to xanthine, subsequently
      producing uric acid. The enzyme complex exists in separate but interconvertible
      forms, xanthine dehydrogenase (XDH) and xanthine oxidase (XOD). XOD is one of the
      major cellular sources of superoxide production and is well known as a causative
      factor in ischemia/reperfusion damage. At present, almost no information on the
      conversion status is available with respect to aging. In the present study, we
      investigated the effect of age on the XOD/XDH status and gene expression in the
      kidney. In addition, we assessed XOD-induced reactive oxygen species (ROS) using
      the dichlorofluoroscein (DCF) method. Our results show that XD activity gradually
      up to 18 months of age and then a slight decrease at 24 months of age. XDH
      activity showed increases up to 18 months of age, then decreased at 24 months of
      age. The conversion of XDH to XOD, assessed by changes in the ratios of
      XOD/(XOD+XDH), showed an age-related increase, which peaked at 24 months. Levels
      of XD protein and its mRNA paralleled to overall XD activity. ROS generation has
      tendency to increase with age. Our results suggest that the increased conversion
      of XDH to XOD observed with age may be an important contributing factor to the
      increased renal oxidative stress during aging.

PMID- 10888480
TI  - A brief training program on resident assessment instrument improves motivation of
      nursing home staff.
AB  - The Resident Assessment Instrument (RAI) has been designed to improve the quality
      of assessment and care in nursing home patients through a better understanding of
      resident needs. We organized three short courses (two weeks) on RAI, involving
      sixty-six nursing home health professionals. The course provided students both a
      theoretical and practical knowledge of RAI. At the end of the program,
      participants were asked to answer to an anonymous questionnaire about the course
      itself and their future professional motivation. The participants showed
      increased motivation and attitudes toward the elderly care. The good results
      obtained indicates that RAI not only may improve quality of nursing home care,
      but it is also an useful tool in the training of geriatric professionals
      enhancing their motivation and job satisfaction.

PMID- 10888481
TI  - Effect of food intake pattern on all-cause mortality in the community elderly: a
      7-year longitudinal study.
AB  - The purpose of the present study was to examine the relationship of a food
      frequency pattern and survivorship in a cohort of community elderly residents
      (259 men, 445 women), aged 65 years old and over, based on a 7-year follow up
      study. Baseline survey was undertaken in July 1988 by door-to-door method. The
      cohort was followed up until August 1995, during which time survivorship of
      subjects was investigated periodically each year. Eighty-one men (31.3%) and 71
      women (19.1%) died during the follow-up period. The food frequency pattern was
      examined by factor analysis based on a food frequency questionnaire for 15 food
      groups at the baseline survey. Results obtained were as follows: 1)The first
      factor was expressive of frequent intake pattern of plant foods, the second
      factor was frequent intake pattern of meat, fat, and oil, the third factor was
      frequent intake pattern of bread and rice(negative), and the fourth factor was
      frequent intake pattern of salty pickled vegetables, fish, and shellfish. 2)The
      first factor as represented by frequent intake pattern of plant foods had
      significant negative effect on all-cause mortality for both the whole 7 years and
      the last 4 years surveys, adjusted for age, sex, education level, drinking habit,
      smoking habit, exercise habit, history of hypertension, and instrumental
      activities of daily living.

PMID- 10888482
TI  - Correlation of dietary food intakes and serum lipid fatty acids in urban senior
      citizens.
AB  - Fatty acid compositions of serum lipids from elderly people (65 to 79 years old)
      in Koganei City of Tokyo were determined, and their correlation with dietary food
      intakes were examined. Cholesterol esters, triglycerides and lecithin revealed
      characteristic fatty acid profiles, respectively. Lecithin contained large
      amounts of eicosapentanoic and docosahexanoic acids (EPA and DHA) which belong to
      n-3 fatty acids as compared to other lipids. Sex differences in the fatty acid
      composition were found only in lecithin among serum lipids. Percentages of n-3
      fatty acids were higher in males than in females, and were found to be positively
      correlated with the intake of fish. On the other hand, linoleic acid and n-6
      fatty acids were shown to have positive correlations with beans. Arachidonic acid
      among n-6 had weak but significant correlations with eggs and milk.

PMID- 10888483
TI  - Elderly men living alone: are they at high nutritional risk?
AB  - This review article investigates the influence of living arrangements on the
      dietary intake and nutritional status of elderly men. Elderly men living alone
      have been identified as a group particularly at risk of poor dietary habits,
      however available evidence is inconsistent. Data from the United States suggests
      that low income elderly men living alone are at high risk of an inadequate
      dietary intake, and that a low energy intake is the most important predictor of a
      poor quality diet in this group. In Australia, older men living with a spouse
      have a better quality diet (higher nutrient density) than those living alone or
      with a person or persons other than a spouse, particularly regarding fruit and
      vegetable intake; differences in nutrient intake are not explained by lower
      energy intakes. In contrast, older men in European countries who live alone
      appear to have a more favourable dietary intake as compared to their counterparts
      in other living arrangements. Information on the association between living
      arrangements and household food security in the elderly in developing countries
      is sparse, however single living among older men is rare and the ethos of the
      extended family appears to remain intact. The inconsistencies in the apparent
      level of nutritional risk associated with living alone in elderly men in
      different countries necessitates the development and validation of screening
      programmes and nutrition services which are country-specific.

PMID- 10888484
TI  - Masticatory ability in relation to oral status and general health on aging.
AB  - In recent years in the field of clinical dentistry, and particularly in
      gerodontics, there has been a growing awareness of the importance of nutrition.
      Because a lack of masticatory ability leads to an impaired nutritional status,
      the dentist must be abreast of current knowledge on masticatory ability. Although
      there are many approaches to the measurement of masticatory ability with natural
      or functional teeth, there is no ideal method for this measurement in the
      elderly. This is because the elderly are usually missing more than half of their
      teeth, and thus have various dentitions. For example, the dentition of 70-years
      old subjects varies from no missing teeth to no remaining teeth. Moreover, the
      prosthetic appliances used vary from partial dentures to complete dentures. The
      present study was performed to establish a method for the objective assessment of
      masticatory ability which could be applied to the elderly, with their various
      dentitions. We demonstrated a useful jelly of varying hardness (G-1 jelly) for
      this assessment. In addition, we examined the correlation between masticatory
      ability, oral status and general health of the elderly, using this new assessment
      method.

PMID- 10888485
TI  - The management of dehydration in the nursing home.

PMID- 10888486
TI  - Soy glycinin: influence of pH and ionic strength on solubility and molecular
      structure at ambient temperatures.
AB  - This study describes the relationship between the solubility of glycinin, a major
      soy protein, and its structural properties at a quaternary, tertiary, and
      secondary folding level under conditions representative for food products. When
      the ionic strength is lowered from 0.5 to 0.2 or 0.03, the basic polypeptides
      shift more to the exterior of the glycinin complex, as determined at pH 7.6 by
      labeling solvent-exposed lysines, supported by the study of the proteolytic
      action of clostripain on glycinin. This structural reorganization caused the pH
      of minimal solubility to shift to higher values. Ultracentrifugational analysis
      shows that at pH 7.6 and an ionic strength of 0.5 glycinin forms hexameric
      complexes (11S), whereas at pH 3.8 and at an ionic strength of 0.03 glycinin
      exists as trimers (7S). Intermediate situations are obtained by modulation of pH
      and ionic strength. The observed quaternary dissociation correlates with an
      increased amount of nonstructured protein at a secondary level and with changes
      in tertiary folding as determined using circular dichroism. Tryptophan
      fluorescence shows no significant structural changes for different ionic
      strengths but demonstrates a more tightly packed fluorophore environment when the
      pH is lowered from 7.6 to 3.8.

PMID- 10888487
TI  - Heat denaturation of soy glycinin: influence of pH and ionic strength on
      molecular structure.
AB  - The 7S/11S glycinin equilibrium as found in Lakemond et al. (J. Agric. Food Chem.
      2000, 48, xxxx-xxxx) at ambient temperatures influences heat denaturation. It is
      found that the 7S form of glycinin denatures at a lower temperature than the 11S
      form, as demonstrated by a combination of calorimetric (DSC) and circular
      dichroism (CD) experiments. At pH 7.6, at which glycinin is mainly present in the
      11S form, the disulfide bridge linking the acidic and the basic polypeptides is
      broken during heat denaturation. At pH 3.8, at which glycinin has dissociated
      partly into the 7S form, and at pH 5.2 this disruption does not take place, as
      demonstrated by solubility and gel electrophoretic experiments. A larger exposure
      of the acidic polypeptides (Lakemond et al., 2000) possibly correlates with a
      higher endothermic transition temperature and with the appearance of an
      exothermic transition as observed with DSC. Denaturation/aggregation (studied by
      DSC) and changes in secondary structure (studied by far-UV CD) take place
      simultaneously. Generally, changes in tertiary structure (studied by near-UV CD)
      occur at lower temperatures than changes in secondary structure.

PMID- 10888488
TI  - Contribution of proanthocyanidins to the peroxy radical scavenging capacity of
      some Italian red wines.
AB  - Highly reactive radicals, ROO(*), were generated from 2, 2'-azobis[2-(2
      imidazolin-2-yl)propane] and linoleic acid. The ROO(*) scavenging capacity of
      some Italian red wines was evaluated following the changes in oxygen consumption.
      Under the experimental conditions the time course of oxygen consumption shows two
      typical behaviors: trolox-like (class I) and gallic acid-like (class II). Usually
      the time course of wine was similar to that of gallic acid. The rate of oxygen
      consumption was found to decrease exponentially with the amount of wine or gallic
      acid added to the test solution. On this basis the capacity of red wines to
      scavenge peroxy radicals was expressed as content of gallic acid (S(GA)). The
      S(GA) values were found to be correlated to the amount of total proanthocyanidins
      and total polyphenols of some Italian red wines (p < 0.01). The proanthocyanidins
      extracted from seeds were shown to make a major contribution to the peroxy
      radical scavenging capacity of red wines, whereas, interestingly, the chemical
      class of the low molecular weight tannins reactive to vanillin did not correlate
      with the S(GA) values.

PMID- 10888489
TI  - Demonstration of pectic polysaccharides in cork cell wall from Quercus suber L.
AB  - Scanning electron microscopy (SEM) and chemical analysis were used to observe the
      cell wall changes that occur in cork with "mancha amarela", when compared to a
      standard cork. To mimic the microbial attack exhibited in cork with mancha
      amarela, the standard cork was treated enzymatically with commercial pectinase
      and hemicellulase preparations. The tissues treated with pectinase were
      comparable with those attacked with mancha amarela. Both were composed by
      deformed and wrinkly cells and exhibited cell wall separation at the middle
      lamella level, which suggests solubilization/removal of the pectic
      polysaccharides. The cork cell wall material, prepared as alcohol-insoluble
      residue, was fractionated by hot water (Pect(H)()2(O)) and hot dilute acid
      (Pect(acid)). The relatively large amount of hexuronic acid and the occurrence of
      Ara in the SPect(H)()2(O) and SPect(acid) allow to confirm, as far as we know,
      for the first time the presence of pectic polysaccharides in the cell walls of
      cork from Quercus suber L. They accounted for ca. 1.5% of the cork and may
      consist of polymers with long side chains of arabinosyl residues. These polymers
      have to be taken into account in any realistic model of the cork cell wall. Cork
      with mancha amarela contained a smaller amount of pectic polysaccharides (ca.
      0.5%), which confirms that the cellular separation observed by SEM is related to
      the degradation/removal of the middle lamella pectic polysaccharides.

PMID- 10888490
TI  - Antioxidant activity and total phenolics in selected cereal grains and their
      different morphological fractions.
AB  - The purpose of this study was to examine the antioxidant properties of water and
      80% methanolic extracts of cereal grains and their different morphological
      fractions. Wheat (Triticum aestivum L.) cv. Almari and cv. Henika, barley
      (Hordeum vulgare L.) cv. Gregor and cv. Mobek, rye (Secale cereale L.) cv.
      Dankowskie Zlote, oat (Avena sativa L.) cv. Slawko and buckwheat (Fagopyrum
      esculentum Moench) cv. Kora were used. PC (L-alpha-phosphatidylcholine) liposome
      system and spectrophotometric assay of total antioxidant activity (TAA) were used
      to evaluate the antioxidative activity of extracts. Among the water extracts,
      only the one prepared from buckwheat exhibited antioxidant activity at the
      concentration analyzed. The following hierarchy of antioxidant activity was
      provided for 80% methanolic extracts originated from whole grain: buckwheat >
      barley > oat > wheat congruent with rye. The antioxidant activity was observed in
      extract prepared from separated parts of buckwheat and barley. In respect to
      hulls, the antioxidant hierarchy was as follows: buckwheat > oat > barley. The
      correlation coefficient between total phenolic compounds and total antioxidative
      activity of the extracts was -0.35 for water extracts and 0.96, 0.99, 0.80, and
      0.99 for 80% methanolic extracts originated from whole grains, hulls, pericarb
      with testa fractions and endosperm with embryo fractions, respectively.

PMID- 10888491
TI  - Endoxylanases in durum wheat semolina processing: solubilization of
      arabinoxylans, action of endogenous inhibitors, and effects on rheological
      properties.
AB  - Endoxylanases seriously affect the rheological properties of durum wheat
      (Triticum durum Desf.) semolina spaghetti doughs prepared with, and as evaluated,
      by the farinograph. Under the experimental conditions, control doughs (34.9%
      moisture content) made from two semolinas (semA and semB) yielded a maximal
      consistency of 525 and 517 farinograph units (FU), with, respectively, 19.4 and
      16.4% of the total level of arabinoxylans (TOT-AX) being water-extractable (WE
      AX). When 75.4 Somogyi units/50 g of semolina of the endoxylanases from
      Trichoderma viride (XTV), rumen microorganisms (XRM), Bacillus subtilis (XBS),
      and Aspergillus niger (XAN) were used, the maximal consistencies at 34.9%
      moisture decreased for semA to 467, 436, 448, and 417 FU, respectively. This was
      accompanied by increased WE-AX contents of 60.8, 71.2, 70.7, and 73.0%,
      respectively. Similar results were observed for semB. By reducing the total water
      content of doughs, it was possible to recover the maximal consistency of the
      original doughs. Both the decrease in maximal consistency and the amount of water
      to be omitted were significantly related to the decrease in molecular weight (MW)
      of the WE-AX and the percentage of WE-AX solubilized as a result of the enzymic
      action. At the same time, it was clear that endogenous endoxylanase inhibitors
      were present in the durum wheat semolinas and that they inhibited the
      endoxylanases used to different degrees. Part of the differences in effects
      between the different endoxylanases (decrease in maximal consistency, amount of
      AX solubilized, MWs of the WE-AX, and amount of water that could be omitted)
      could be ascribed to the differences in inhibition of the endoxylanases by
      endogenous inhibitors.

PMID- 10888492
TI  - Physical properties of shark gelatin compared with pig gelatin.
AB  - Physical properties of shark gelatin were examined during gel formation and
      postgelation in comparison with pig gelatin. Samples with various concentrations
      and pH values were evaluated by breaking strength, dynamic viscoelasticity, and
      dynamic light scattering. Sol-gel and gel-sol transition temperatures for shark
      gelatin were remarkably lower than those for pig gelatin. Shark gelatin gel shows
      a narrower pH range to form a stable gel compared with pig gelatin. Melting
      enthalpy of shark gelatin gel was greater than that of pig gelatin gel, and G' of
      shark gelatin gel changed more extensively with rising temperature in comparison
      with pig gelatin gel. It is concluded that shark gelatin has different
      characteristics from pig gelatin not only for gel characteristics but also for
      the solution property.

PMID- 10888493
TI  - The physicochemical property of shark type I collagen gel and membrane.
AB  - The physicochemical properties of shark type I collagen gel and membrane were not
      same as those of pig type I collagen. The denaturation temperature of shark
      collagen gel was about 15 degrees C lower. According to scanning electronic
      micrography, the diameter of shark collagen fibril was relatively thin and more
      homogeneous. The breaking strength of shark collagen gel was greater, and shark
      collagen membrane had a greater mechanical strength and a higher water vapor
      sorption.

PMID- 10888494
TI  - Acid-catalyzed hydrolysis of alcohols and their beta-D-glucopyranosides.
AB  - The hydrolysis, in model wine at pH 3, of the allylic, homoallylic, and
      propargylic glycosides, geranyl-beta-D-glucopyranoside, [3'-(1' '-cyclohexenyl)
      1'-methyl-2'-propynyl]-beta-D-glucopyranoside, (3'RS, 9'SR)-(3'-hydroxy-5'
      megastigmen-7-yn-9-yl)-beta-D-glucopyra noside, (3',5',5'-trimethyl-3'
      cyclohexenyl)-beta-D-glucopyranoside, E-(7'-oxo-5',8'-megastigmadien-3'-yl)-beta
      D-glucopyranoside (3-hydroxy-beta-damascone-beta-D-glucopyranoside), and their
      corresponding aglycons has been studied. In general, aglycons were more rapidly
      converted to transformation products than were the corresponding glucosides.
      Glycoconjugation of geraniol in grapes is a process that reduces the flavor
      impact of this compound in wine, not only because geraniol is an important flavor
      component of some wines but also because the rate of formation of other flavor
      compounds from geraniol during bottle-aging is reduced. However, when flavor
      compounds such as beta-damascenone are formed in competition with flavorless
      byproducts, such as 3-hydroxy-beta-damascone, by acid-catalyzed hydrolytic
      reactions of polyols, then glycoconjugation is a process that could enhance as
      well as suppress the formation of flavor, depending on the position of
      glycosylation. (3'RS, 9'SR)-(3'-Hydroxy-5'-megastigmen-7'-yn-9'-yl)-beta-D
      glucopy ranoside hydrolyzed more slowly but gave a higher proportion of beta
      damascenone in the products than did the aglycon at 50 degrees C. Reaction
      temperature also effected the relative proportion of the hydrolysis products.
      Accelerated studies do not parallel natural processes precisely but only
      approximate them.

PMID- 10888495
TI  - Temperature-dependent autoxidation of conjugated trienols from apple peel yields
      6-methyl-5-hepten-2-one, a volatile implicated in induction of scald.
AB  - Conjugated triene (CT) oxidation products of alpha-farnesene have long been
      thought to be involved in development of superficial scald in apple fruit. Early
      studies found that CT hydroperoxides and the volatile 6-methyl-5-hepten-2-one
      (MHO) are major in vitro autoxidation products of alpha-farnesene. However, it
      was recently shown that > or =99% of the oxidation products of alpha-farnesene
      that accumulate in apple peel are conjugated trienols (CTols), isomers of 2,6,10
      trimethyldodeca-2,7,9,11-tetraene-6-ol. HPLC-purified CTols from fruit of two
      scald-susceptible cultivars, Granny Smith (GS) and Red Delicious (RD), were used
      to study autoxidation of these compounds in vitro. Incubation of CTols in sealed
      glass vials under air resulted in accumulation of MHO. Oxygen enrichment did not
      increase the amount of MHO produced. Regardless of which cultivar CTols were
      derived from, at 0 degrees C autoxidation yielding MHO was quite slow and linear,
      whereas at 20 degrees C MHO production was much more rapid, and after several
      hours the rate increased abruptly. However, CTols isolated from GS and RD fruit
      differed in the duration of the initial lag phase and the overall level of MHO
      generated at 20 degrees C. The sharp increase in MHO production occurred after 3
      h with GS CTols and at about 12 h with RD CTols. Also, the yield of MHO from GS
      CTols after 6 h at 20 degrees C was nearly 6-fold greater than that from RD CTols
      after 20 h at 20 degrees C. The antioxidants butylated hydroxytoluene and
      diphenyamine reduced the yield of MHO by about 97%. Recent work has shown that
      MHO can induce scald-like symptoms in apple peel and that tissue sensitivity
      increases with time in storage. This may explain the correlation between high
      CTol levels and scald development, and why symptoms rapidly intensify when fruits
      are removed from cold storage.

PMID- 10888496
TI  - Lysozyme-glucose stearic acid monoester conjugate formed through the Maillard
      reaction as an antibacterial emulsifier.
AB  - Lysozyme-glucose stearic acid monoester (HEL-GE) conjugate was prepared through
      the Maillard reaction as an antibacterial emulsifier. The molar ratio of GE to
      HEL was 1:1. The isoelectric point was 6-7, which is lower than that of native
      HEL. Spectroscopic studies indicated that the alpha-helix content was slightly
      lower but the conformation around Trp had not changed and that the surface of the
      conjugate was covered with the GE moiety. The conjugate maintained approximately
      53-57% of the enzymatic activity of native HEL at 40-60 degrees C and exhibited
      considerable resistance to proteolysis. The denaturation temperature of the
      conjugate was approximately 74 degrees C, somewhat higher than that of control
      HEL, whereas the enthalpy was about one-third of that of control HEL. The
      emulsifying activity of the conjugate and the emulsion stability were much
      enhanced compared to those of native HEL, and the conjugate maintained
      approximately 70% of the bactericidal activity.

PMID- 10888497
TI  - Functional changes in beta-lactoglobulin by conjugation with cationic
      saccharides.
AB  - Bovine beta-lactoglobulin (beta-LG) was conjugated to each of three cationic
      saccharides [glucosamine (GlcN), chitopentaose (CPO), and chitosan (CHS)] by
      means of a water-soluble carbodiimide or by the Maillard reaction in an effort to
      improve the functional properties of beta-LG. The molar ratios of beta-LG to the
      cationic saccharide in the beta-LG-GlcN, beta-LG-CPO, and beta-LG-CHS conjugates
      were 2:1, 2:5, and 2:1, respectively. Fluorescence studies indicated that the
      conformation around Trp had changed in each conjugate and that the surface of
      each of the conjugates was covered with a saccharide chain. Structural analysis
      using monoclonal antibodies indicated that the conformation around (15)Val
      (29)Ile (beta-sheet region) in beta-LG-GlcN and beta-LG-CPO had changed but that
      in beta-LG-CHS was maintained, whereas the conformation around (125)Thr-(135)Lys
      (alpha-helix region) in the conjugates had changed. The emulsifying activity of
      beta-LG was improved by conjugation with CPO or CHS, and aggregation of beta-LG
      was suppressed by conjugation with CHS. Reduction of the antigenicity and
      immunogenicity of beta-LG was achieved by conjugation with CHS.

PMID- 10888498
TI  - Ability of surfactant headgroup size to alter lipid and antioxidant oxidation in
      oil-in-water emulsions.
AB  - Oxidation of oil-in-water emulsion droplets is influenced by the properties of
      the interfacial membrane surrounding the lipid core. To evaluate how surfactant
      headgroup size influences lipid oxidation rates, emulsions were prepared with
      polyoxyethylene 10 stearyl ether (Brij 76) or polyoxyethylene 100 stearyl ether
      (Brij 700), which are structurally identical except for their hydrophilic
      headgroups, with Brij 700 containing 10 times more polyoxyethylene groups than
      Brij 76. Fe(2+)-promoted decomposition of cumene hydroperoxide was lower in Brij
      700-stabilized than in Brij 76-stabilized hexadecane emulsions. Fe(2+)-promoted
      alpha-tocopherol oxidation rates were similar in hexadecane emulsion regardless
      of surfactant type. Brij 700 decreased production of hexanal from methyl
      linoleate and the formation of lipid peroxides and propanal from salmon oil
      compared to emulsions stabilized by Brij 76. These results indicate that emulsion
      droplet interfacial thickness could be an important determinant in the oxidative
      stability of food emulsions.

PMID- 10888499
TI  - Chemical speciation influences comparative activity of selenium-enriched garlic
      and yeast in mammary cancer prevention.
AB  - A recent human intervention trial showed that daily supplementation with
      selenized yeast (Se-yeast) led to a decrease in the overall cancer morbidity and
      mortality by nearly 50%; past research has also demonstrated that selenized
      garlic (Se-garlic) is very effective in mammary cancer chemoprevention in the rat
      model. The goal of this study was to compare certain biological activities of Se
      garlic and Se-yeast and to elucidate the differences based on the chemical forms
      of selenium found in these two natural products. Characterization of organic
      selenium compounds in yeast (1922 microg/g Se) and garlic (296 microg/g Se) was
      carried out by high-performance liquid chromatography with inductively coupled
      plasma mass spectrometry or with electrospray mass spectrometry. Analytical
      speciation studies showed that the bulk of the selenium in Se-garlic and Se-yeast
      is in the form of gamma-glutamyl-Se-methylselenocysteine (73%) and
      selenomethionine (85%), respectively. The above methodology has the sensitivity
      and capability to account for >90% of total selenium. In the rat feeding studies,
      supplementation of Se-garlic in the diet at different levels consistently caused
      a lower total tissue selenium accumulation when compared to Se-yeast. On the
      other hand, Se-garlic was significantly more effective in suppressing the
      development of premalignant lesions and the formation of adenocarcinomas in the
      mammary gland of carcinogen-treated rats. Given the present finding on the
      identity of selenomethionine and gamma-glutamyl-Se-methylselenocysteine as the
      major form of selenium in Se-yeast and Se-garlic, respectively, the metabolism of
      these two compounds is discussed in an attempt to elucidate how their disposition
      in tissues might account for the differences in cancer chemopreventive activity.

PMID- 10888500
TI  - Kinetic study of oxalic acid inhibition on enzymatic browning.
AB  - Oxalic acid has a strong antibrowning activity. The inhibitory pattern on
      catechol-PPO model system appeared to be competitive, with a K(i) value of 2.0
      mM. When the PPO was incubated with oxalic acid, the activity was not recovered
      via dialysis, but the inactivated enzyme partially recovered its activity when
      cupric ion was added. Comparing the relative antibrowning effectiveness of oxalic
      acid with other common antibrowning agents, oxalic acid with I(50) value of 1.1
      mM is as effective as kojic acid and more potent than cysteine and glutathione.

PMID- 10888501
TI  - Change in carotenoids and antioxidant vitamins in tomato as a function of
      varietal and technological factors.
AB  - The change in the carotenoid and bioantioxidant content of tomato as a function
      of varietal and technological factors was investigated in the present work. No
      great differences were found between cultivars for fresh consumption (salad
      tomatoes) and those for processing in ascorbic acid content. The concentration of
      ascorbic acid ranged between 14.6 and 21.7 mg/100 g fresh weight of ripe tomato
      fruit. Processing cultivars contained higher amounts of tocopherols, particularly
      alpha-tocopherol than tomatoes for fresh consumption. Significant differences
      could be obtained between the examined varieties with regard to carotenoid
      concentration. The different tomatoes varied not only in the total carotenoid
      content but also in the qualitative distribution of some pigments such as
      lycopene, beta-carotene and lutein. During heat-based processing, ascorbic acid,
      tocopherols, and carotenoids showed different role and response. Ascorbic acid,
      alpha-tocopherol quinone, and beta-carotene were the most susceptible components
      toward thermal degradation.

PMID- 10888502
TI  - Effect of heat treatment on nutritional quality of germinated legume seeds.
AB  - The effect of heat treatment of germinated soybean, lupin, and black bean on
      chemical composition and protein utilization in rats was evaluated. Heat
      treatment caused complete inactivation of trypsin inhibitors whereas it did not
      affect phytic acid levels. Proximate components, minerals, and amino acids did
      not change, but low molecular weight sugars were affected by heat treatment
      differently for each germinated legume. The sugar digestibility ratio (total
      digestible sugars/total nondigestible sugars) in germinated black beans doubled
      after heat treatment. True protein digestibility (TD) increased with heat
      treatment only in germinated soybean. Net protein utilization was markedly
      improved (20%) with heat treatment in germinated soybean and lupin. Utilizable
      protein of heat-treated germinated legumes was 289, 236, and 132 g/kg of legume
      dry weight for soybean, lupin, and black bean, respectively. Supplementation with
      methionine did not alter TD but improved all other indices of protein utilization
      in the germinated legumes, particularly in black bean. All three germinated
      legumes become equivalent in protein quality when heating and supplementation
      with methionine are combined with germination. The use of germinated heat-treated
      soybean, lupin, and black bean on their own and/or as food ingredients is
      nutritionally advantageous due to the low content of nondigestible
      oligosaccharides and the high protein utilization.

PMID- 10888503
TI  - Polyclonal-antibody-based ELISA to detect milk alkaline phosphatase.
AB  - Polyclonal antibodies (PAb) prepared against bovine milk alkaline phosphatase
      (ALP) were used to develop a competitive indirect (CI) ELISA. Anti-ALP PAb were
      specific for milk ALP and did not react with ALP from E. coli or bovine and calf
      intestinal mucosa. Anti-ALP PAb were 20% cross-reactive with bovine placenta ALP.
      The anti-ALP antibodies also did not recognize bovine serum albumin, acid
      glycoprotein, ovalbumin, ferritin, and casein, although some cross-reactivity was
      observed with whey protein isolate. Anti-ALP PAbs reacted with deglycosylated
      native ALP, but did not recognize ALP denatured at 100 degrees C in 2% SDS or
      deglycosylated denatured ALP. When buffered solutions of milk ALP were heated at
      70 degrees C, ALP activity decreased at a faster rate than ALP content determined
      by CI-ELISA. The ELISA differentiated between native and heat denatured ALP.
      Further studies are warranted to determine if an ELISA can be used to verify
      pasteurization of fluid milk.

PMID- 10888504
TI  - Cloning and expression of a cDNA coding for catalase from zebrafish (Danio
      rerio).
AB  - A full-length complementary DNA (cDNA) clone encoding a catalase was amplified by
      the rapid amplication of cDNA ends-polymerase chain reaction (RACE-PCR) technique
      from zebrafish (Danio rerio) mRNA. Nucleotide sequence analysis of this cDNA
      clone revealed that it comprised a complete open reading frame coding for 526
      amino acid residues and that it had a molecular mass of 59 654 Da. The deduced
      amino acid sequence showed high similarity with the sequences of catalase from
      swine (86.9%), mouse (85.8%), rat (85%), human (83.7%), fruit fly (75.6%),
      nematode (71.1%), and yeast (58.6%). The amino acid residues for secondary
      structures are apparently conserved as they are present in other mammal species.
      Furthermore, the coding region of zebrafish catalase was introduced into an
      expression vector, pET-20b(+), and transformed into Escherichia coli expression
      host BL21(DE3)pLysS. A 60-kDa active catalase protein was expressed and detected
      by Coomassie blue staining as well as activity staining on polyacrylamide gel
      followed electrophoresis.

PMID- 10888505
TI  - Optimization of tannin extraction from infant foods.
AB  - The design of experiments (DOE) was used in the development of a laboratory
      procedure for the extraction of tannins from three infant food types comprising
      different ingredients of vegetable origin and meat. The diversity of vegetables
      included in the product formulas required the use of DOE to establish parameters
      that maximize the recovery of tannins using a central composite rotatable design.
      Once the experimental results from the DOE were obtained, response surface
      methodology was used to find the best analytical conditions for samples
      comprising different ingredients. Sample weight was found to be a critical factor
      in tannin extraction from foods. Different optimal conditions were obtained for
      samples including soya in the formula.

PMID- 10888506
TI  - Effect of pH on the stability of plant phenolic compounds.
AB  - It is not uncommon to treat plant-derived foods and feeds with alkali. Such
      exposure to high pH is being used to recover proteins from cereals and legumes,
      to induce the formation of fiber-forming meat analogue vegetable protein, for
      preparing peeled fruits and vegetables, and for destroying microorganisms. In
      addition to their profound effects on functional and nutritional properties in
      such foods, such treatments may also cause other side reactions, including the
      destruction of natural polyphenolic compounds. Because plants contain a large
      number of structurally different antioxidant, anticarcinogenic, and antimicrobial
      polyphenolic compounds, it is of interest to know whether such compounds are
      stable to heat and to high pH. In this model study, the stability of the
      following natural polyphenols to pH in the range 3-11 was studied with the aid of
      ultraviolet spectroscopy: caffeic acid, (-)-catechin, chlorogenic acid, ferulic
      acid, gallic acid, (-)-epigallocatechin, rutin, and the nonphenolic compound
      trans-cinnamic acid. This study demonstrates that caffeic, chlorogenic, and
      gallic acids are not stable to high pH and that the pH- and time-dependent
      spectral transformations are not reversible. By contrast, chlorogenic acid is
      stable to acid pH, to heat, and to storage when added to apple juice. (-)
      Catechin, (-)-epigallocatechin, ferulic acid, rutin, and trans-cinnamic acid
      resisted major pH-induced degradation. The results are rationalized in terms of
      relative resonance stabilization of phenoxide ions and quinone oxidation
      intermediates. The possible significance of these findings to food chemistry and
      microbiology is discussed.

PMID- 10888507
TI  - Formation of tetrahydro-beta-carbolines and beta-carbolines during the reaction
      of L-tryptophan with D-glucose.
AB  - The reaction of L-tryptophan (Trp) with D-glucose under conditions that can occur
      during food processing and preparation was studied by high-performance liquid
      chromatography with diode array detection (HPLC/DAD). Besides the well
      established glucose-tryptophan Amadori product (AP), (1R,3S)-1-(D-gluco-1,2,3,4,5
      pentahydroxypentyl)-1,2,3, 4-tetrahydro-beta-carboline-3-carboxylic acid (PHP
      THbetaC) was identified as an important product of this reaction. For
      preparation, PHP-THbetaC was obtained in high yields when Trp and D-glucose were
      reacted under strongly acidic conditions after heating in methanol. At elevated
      reaction temperatures (150 degrees C) 1-acetyl-beta-carboline (acetyl-betaC), was
      detected in significant concentrations. The mixtures were heated under variations
      of reaction time and temperature, and AP, PHP-THbetaC, and acetyl-betaC were
      quantified. In the presence of air oxygen or mild, food relevant oxidants, such
      as L-dehydroascorbic acid, PHP-THbetaC was readily oxidized to a product that was
      identified as the previously unknown 1-(D-gluco-1,2,3,4,5-pentahydroxypentyl)
      beta-carboline (PHP-betaC). Formation of PHP-THbetaC and PHP-betaC in foodstuffs
      would deserve particular interest because multiple physiological activity of
      THbetaC and betaC derivatives has been shown previously.

PMID- 10888508
TI  - Comparison of antioxidant enzyme activities between Solanum tuberosum L.
      Cultivars Danshaku and Kitaakari during low-temperature storage.
AB  - We compared the antioxidant enzyme activities between Solanum tuberosum L.
      cultivars Kitaakari and "Danshaku" during storage at 1 degrees C and 20 degrees
      C. The Kitaakari and Danshaku plants contained approximately 330 microM and 120
      microM ascorbic acid (AsA) immediately after the harvest, respectively. At 1
      degrees C, the activity of ascorbate peroxidase (APx) in the Kitaakari plants
      showed the tendency to increase, while in the Danshaku its activity increased
      temporally by 9 weeks and thereafter returned to basal levels. Superoxide
      dismutase (SOD) activity increased after 12 weeks in the case of the Kitaakari at
      1 degrees C. Catalase did not show any difference in both cultivars at each
      temperature. The contents of AsA, which was one of the substrates of APx,
      decreased more rapidly at 1 degrees C than at 20 degrees C in both cultivars.
      Particularly in the case of the Danshaku, AsA contents were already less than 30
      microM at 9 weeks, which confirmed that APx was inactivated.

PMID- 10888509
TI  - Phenolic acids and derivatives: studies on the relationship among structure,
      radical scavenging activity, and physicochemical parameters.
AB  - The antiradical activity of caffeic acid (1), dihydrocaffeic acid (5), and their
      corresponding n-alkyl esters was evaluated by using the 2,2-diphenyl-1
      picrylhydrazyl radical (DPPH(*)) method. Dihydrocaffeic acid (5) was the most
      potent compound, having an antiradical effect higher than that of (+/-)-alpha
      tocopherol, whereas caffeic acid (1) was less efficient. Esterification of the
      carboxyl group of dihydrocaffeic acid (5) had a dramatic effect on its
      antiradical potency, but similar effects were not observed for caffeic acid (1)
      derivatives. The n-alkyl esters of both phenolic series had similar potencies,
      and their antiradical activities were independent of the alkyl chain length. Dose
      dependent scavenger effects were found in both series. Acid-base properties of
      the compounds, evaluated by using potentiometry and spectrophotometry, showed
      that the catechol moiety had pK(a2) and pK(a3) values of 9. 24-9.02 and 11.38
      10.99 in the dihydrocaffeic series and 8.48-8.24 and 11.38-11.07 in the caffeic
      series, respectively. Antiradical activity and pK(a) values of the compounds were
      not related.

PMID- 10888510
TI  - Kinetics of oxidation of the lipids and proteins of cod sarcoplasmic reticulum.
AB  - Lipid and protein oxidation in an NADH-Fe enzymic and an ascorbate-Fe nonenzymic
      system were determined simultaneously. The nonenzymic iron-reducing system gave
      rapid oxidation of lipid that leveled off at values much lower than those
      achieved in the enzymic system, which showed a continuous increase over the 1 or
      2 h incubation times used. Protein sulfhydryl oxidation was more rapid in the
      nonenzymic system for total and accessible sulfhydryl groups, but the enzymic
      system oxidized the inaccessible sulfhydryl groups more rapidly. Both lipid and
      protein oxidations appeared to begin simultaneously. In the enzymic system, more
      lipid oxidation was achieved on a molar basis than oxidation of protein
      sulfhydryl groups, while in the nonenzymic system this was reversed. These data
      probably reflect the site specificity of the production of oxidizing elements in
      the two systems. The greater lipid oxidation in the enzymic system suggests that
      this may be the more important ferric iron-reducing system during storage of fish
      muscle.

PMID- 10888511
TI  - Effect of storage temperature and pyruvate on kinetics of anthocyanin
      degradation, vitisin A derivative formation, and color characteristics of model
      solutions.
AB  - The formation of vitisin A, an anthocyanin formed naturally in small quantities
      in maturing port wines, was studied in model wine solutions at several storage
      temperatures (10, 15, 20, and 32 degrees C). Vitisin A was formed through the
      interaction between malvidin 3-glucoside and pyruvic acid, Acylated forms of
      vitisin A, having the 6-position of the sugar acylated with acetic acid (3
      acetylvitisin A) and p-coumaric acid (3-p-coumarylvitisin A), were also formed
      through the interaction between pyruvic acid and malvidin 3-acetylglucoside and
      malvidin 3-p-coumarylglucoside, respectively. A maximum degradation of the
      anthocyanins was obtained at higher temperatures, and it followed a first-order
      kinetics both with and without pyruvic acid in the solution. Whereas at low
      temperatures (10 and 15 degrees C) the presence of pyruvic acid accelerated the
      kinetic reaction, at higher temperatures (20 and 32 degrees C) it decreased it.
      The activation energy values for the degradation of the three anthocyanins in
      model solutions without and with pyruvic acid were not significantly different
      from each other. At low temperatures the highest concentrations of vitisin A
      compounds were obtained. All solutions showed a decrease in L value, indicating
      that all solutions became darker. This change increased with increasing
      temperature. All model solutions increased in the hue angle, indicating that the
      solutions changed from a bluish-red to an orange-red or even brownish-red color.
      Samples without pyruvic acid remained lighter and became browner than those with
      pyruvic acid. A good correlation between the amount of vitisin A in the solution
      and hue angle was found, indicating that vitisin A may contribute the orange-red
      of solutions, compared to the browner control.

PMID- 10888512
TI  - Isolation and partial characterization of two types of muscle collagen in some
      cephalopods.
AB  - Collagen from muscle of volador (Illex coindetii), pota (Toradopsis eblanae), and
      white octopus (Eledone cirrhosa) was characterized in terms of anatomical
      location, sex, and maturity. Collagen content was higher in arms than in mantle
      in all three species; there were also significant differences in octopus
      depending on the age of the individual. Concerning sex, the largest differences
      in the amount of collagen were found in relation to total protein content. In
      volador and pota, collagen solubility was higher in the mantle than in the arms,
      and in the case of pota there were also sex-related differences. In octopus
      males, solubility was higher in the arms. Two types of collagen, I and V, were
      identified as the principal constituents in all three species and at both
      anatomical locations (mantle and arms). The electrophoretic mobility of the
      alpha2 chain differed in the two types of collagen, but the amino acid
      compositions of the collagen were similar in the mantle and arms in all three
      species examined.

PMID- 10888513
TI  - Enzymatic formation of ether linkage producing shoyuflavones from genistein and
      (+/-)-trans-epoxysuccinic acid.
AB  - The production mechanism of shoyuflavones, conjugated ethers of isoflavones with
      tartaric acid and isolated from fermented soy sauce, was studied. In the high
      molecular weight fraction of the culture extract of Aspergillus oryzae, genistein
      was transformed into shoyuflavone B in the presence of (+/-)-trans-epoxysuccinic
      acid but not in the low molecular one. Asp. sojae and Asp. tamarii showed high
      activity similar to Asp. oryzae but none of Asp. niger, Rhizopus oligosporus, and
      Mucor praini did. The contents of epoxysuccinic acids in the starting materials
      of soy sauce and the cultures of various Asp. fungi were determined as dimethyl 2
      chloro-3-hydroxysuccinate derivatives by GC-MS. Although epoxysuccinic acids were
      contained in Asp. oryzae, Asp. sojae, and Asp. tamarii cultures, they were not
      found in soybeans and wheat. A possible producing mechanism for shoyuflavones by
      enzymatically conjugating isoflavones to (+/-)-trans-epoxysuccinic acid with
      ether linkage was suggested.

PMID- 10888514
TI  - Phenolic compounds and browning in sherry wines subjected to oxidative and
      biological aging.
AB  - The composition in hydroxybenzoic and hydroxycinnamic acids, hydroxycinnamic
      esters, tyrosol, syringaldehyde, and flavan-3-ol derivatives of three different
      types of sherry wine obtained by aging of the same starting wine under different
      conditions was studied. So-called "fino" wine was obtained by biological aging
      under flor yeasts, "oloroso" wine by oxidative aging, and "amontillado" wine by a
      first stage of biological aging followed by a second oxidative step. On the basis
      of the results, the wines subjected to oxidative aging exhibited higher phenol
      contents, in addition to scarcely polar compounds absorbing at 420 nm that were
      absent in the wines obtained by biological aging. Taking into account that flavan
      3-ol derivatives play an important role in wine browning, a model catechin
      solution was inoculated with flor yeast which, contrary to the findings of other
      authors in the absence of yeasts, formed no colored compounds. This different
      behavior may account for the resistance to browning of pale sherry wines in the
      presence of flor yeasts.

PMID- 10888515
TI  - Acceleration of pH variation in cloudy apple juice using electrodialysis with
      bipolar membranes.
AB  - The purpose of this study was to accelerate pH variation in cloudy apple juice
      using electrodialysis (ED). The testing was conducted using two ED
      configurations. The bipolar and cationic membrane configuration showed that
      reducing the spacing from 8 to 0.75 mm had little effect on treatment time,
      whereas stacking eight bipolar membranes reduced acidification time by 30%,
      although the treatment still took too long (21 min). Furthermore, it was not
      possible to acidify apple juice to a pH of 2.0 to completely inhibit enzymatic
      browning. The bipolar and anionic membrane configuration helped to accelerate the
      acidification step by a factor of 3, increasing the yield from 3.3 to 10 L of
      juice/m(2) membrane/min. Moreover, treatment time was inversely proportional to
      the size of the membrane stack. The speed at which the pH of acidified juice
      returned to its initial value was, however, 4 times slower than the speed of
      acidification, giving a yield of 2.5 L of juice/m(2) membrane/min. By
      accelerating the acidification step, ED treatment with bipolar and anionic
      membranes results in more effective polyphenol oxidase activity and more rapid
      control of juice browning at pH 2.0. Also, the treatment has very little effect
      on the chemical composition and organoleptic quality of apple juice.

PMID- 10888516
TI  - Induction of the soybean phytoalexins coumestrol and glyceollin by Aspergillus.
AB  - Several isoflavonoid phytoalexins produced by soybeans are known to be
      estrogenic, with potential beneficial health effects in humans. Increased
      production of phytoalexins by the soybean plant will facilitate research efforts
      in this area. In this study, phytoalexin induction and accumulation in soybean
      cotyledon tissue was observed using four species of Aspergillus: A. sojae, A.
      oryzae, A. niger, and A. flavus. All four Aspergillus species tested elicited
      phytoalexin accumulation in living soybean cotyledons. Results from a time course
      study indicated that maximum concentrations of the phytoalexin glyceollin, 955
      microg/g fresh weight (fw), occurred at day 3 in soybean cotyledon tissue
      inoculated with A. sojae. Other Aspergillus species caused an accumulation of
      glyceollin at significantly lower levels. A maximum concentration of coumestrol
      of 27.2 microg/g fw was obtained from soybean cotyledons inoculated with A.
      niger. Soybean phytoalexins induced by food-grade A. sojae and A. oryzae allowed
      the collection of higher concentrations of phytoalexins for further examination
      in several in vitro and in vivo biological studies conducted to determine
      potential estrogenic activities.

PMID- 10888517
TI  - Stripped corn oil controls scald and maintains volatile production potential in
      golden supreme and delicious apples.
AB  - Effects of stripped (alpha-tocopherol < 5 mg L(-)(1)) corn oil on flesh firmness,
      skin color, acidity, soluble solids content (SSC), scald, and fruit volatiles
      during 6 months at 0 degrees C were studied using Golden Supreme and Delicious
      apples. Treatment with 10% oil emulsion reduced production of ethylene, alpha
      farnesene, and major volatile esters in the first 3 months of storage, but this
      trend reversed after 5 months. After 6 months at 0 degrees C plus 7 days at 20
      degrees C, oil-treated fruit were firmer and greener and had higher levels of
      titratable acidity than the controls. In addition, control fruit developed 27%
      and 42% scald in Golden Supreme and Delicious apples, respectively, whereas oil
      treated fruit were free from scald. Soluble solids content and ethanol production
      were unaffected by oil treatment.

PMID- 10888518
TI  - Extraction of tricyclazole from soil and sediment with subcritical water.
AB  - The use of subcritical water to extract tricyclazole from soils and sediments was
      examined. Extraction efficiency and kinetics were determined as a function of
      temperature, sample age, sample matrix, sample size, and flow rate. Extraction
      temperature was the most influential experimental factor affecting extraction
      efficiency and kinetics, with increasing temperature (up to 150 degrees C)
      yielding faster and higher efficiency extractions. Higher extraction temperatures
      were also important for quantitative recovery of tricyclazole from aged samples.
      Extraction at 50 degrees C yielded 97% recoveries from samples aged 1 day but
      only 30% recoveries for samples aged 202 days, whereas extraction at 150 degrees
      C yielded recoveries of 85-100% that were independent of incubation time and
      sample matrix, with the exception of one sediment that contained a large amount
      of organic matter. Sample extracts from subcritical water extraction were
      generally a pale yellow color, contrasted with a dark brown color from organic
      solvent extractions of the same matrixes. Less sample cleanup was therefore
      required prior to analysis, with the total time for the extraction and analysis
      of a single sample being approximately 2 h. Subcritical water extraction is an
      effective technique for the rapid and quantitative extraction of tricyclazole
      from soils and sediments.

PMID- 10888519
TI  - Use of restriction fragment length polymorphism to distinguish between salmon
      species.
AB  - Identification of 10 salmon species using DNA-based methodology was investigated.
      Amplification of DNA was carried out using a primer set which amplified a region
      of the mitochondrial cytochrome b gene. Sequences of PCR-amplified DNA from the
      salmon species were used to select six restriction enzymes allowing species to be
      uniquely classified. RFLP patterns generated following analysis with each enzyme
      were resolved using polyacrylamide gel electrophoresis and visualized by silver
      staining. Results indicate that it is possible to differentiate between all 10
      salmon species and that the technique could be easily adopted by the food
      industry for analysis of processed salmon products.

PMID- 10888520
TI  - Supercritical carbon dioxide extraction of turmeric (Curcuma longa).
AB  - Turmeric oil was extracted from turmeric (Curcuma longa) with supercritical
      carbon dioxide in a semicontinuous-flow extractor. Extraction rate was measured
      as a function of pressure, temperature, flow rate, and particle size. The
      extraction rate increased with an increase in CO(2) flow rate and with a
      reduction of particle size. The effect of pressure and temperature on turmeric
      extraction suggested the use of higher pressure and lower temperature at which
      solvent density is greater and thus the solubility of the oil in the solvent is
      greater in the range of 313-333 K and 20-40 MPa. The major components (
      approximately 60%) of the extracted oil were identified as turmerone and ar
      turmerone by GC-MS.

PMID- 10888521
TI  - Near-infrared spectroscopic technique for detection of beef hamburger
      adulteration.
AB  - A near-infrared spectroscopic technique was developed to detect beef hamburgers
      adulterated with 5-25% mutton, pork, skim milk powder, or wheat flour with an
      accuracy up to 92.7%. The accuracy of detection increased with the increase of
      adulteration level. When an adulterant was detected, the adulteration level was
      further predicted by calibration equations. The established calibration equations
      for predicting adulteration levels with mutton, pork, skim milk powder, and wheat
      flour had standard errors of cross-validation of 3.33, 2.99, 0.92, and 0.57% and
      coefficients of variance of 0.87, 0.89, 0.99, and 1.00, respectively. The results
      of this study indicate that near-infrared spectroscopy is potentially useful in
      detection of beef hamburger adulteration.

PMID- 10888522
TI  - Bulk analysis of tobacco and cigarettes by magnetic resonance imaging.
AB  - Proton magnetic resonance imaging of tobacco blends in cigarette rods was
      investigated to assess the feasibility of various imaging protocols to
      characterize and quantify the structure and composition of multiphase plant
      materials in situ. The protocols used to characterize the rigid molecular
      components (plant cell wall) included single-point imaging (SPI) and a variant
      experiment, single-point ramped imaging with T(1) enhancement (SPRITE). Both 1D
      profiles, radially averaged along the length of a cigarette, and 2D maps of
      proton spin density and relaxation (T(2)) were acquired. Mobile components
      (tobacco waxes and water) were examined via conventional spin-echo imaging
      techniques, with 1D, 2D, and 3D data being acquired. Spin-spin relaxation times
      (T(2)), apparent spin-spin relaxation (T(2)), and spin-lattice (T(1)) relaxation
      times were measured for selected samples.

PMID- 10888523
TI  - Supercritical fluid extraction of 2,4,6-trichloroanisole from cork stoppers.
AB  - 2,4,6-Trichloroanisole (TCA) is the compound most often associated with cork
      taint in wines and has been shown to have a very low sensory threshold (
      approximately 5 ng/L in wine). A supercritical fluid extraction (SFE) method for
      TCA in bark cork stoppers was developed with quantification via gas
      chromatography-mass spectrometry with selected ion monitoring. Supercritical
      carbon dioxide functioned as the extracting solvent, and temperature and pressure
      were optimized for the extraction. The method was validated using the stable
      isotope (2)H(5)-TCA as the internal standard. Recovery of TCA from spiked corks
      was found to be within 1-4% of the theoretical concentration with a coefficient
      of variation ranging from 2.6 to 9.7%. TCA levels in corks pulled from wines
      described as tainted by experienced judges ranged from 0.13 to 2.11 microg/g of
      cork. The SFE procedure offers a rapid, quantitative, nearly solvent-free, and
      automated method for the extraction of TCA from complex solid matrices such as
      cork.

PMID- 10888524
TI  - Determination of niclosamide residues in rainbow trout (Oncorhynchus mykiss) and
      channel catfish (Ictalurus punctatus) fillet tissue by high-performance liquid
      chromatography.
AB  - Bayluscide [the ethanolamine salt of niclosamide (NIC)] is a registered piscicide
      used in combination with 3-(trifluoromethyl)-4-nitrophenol (TFM) to control sea
      lamprey populations in streams tributary to the Great Lakes. A high-performance
      liquid chromatography (HPLC) method was developed for the determination of NIC
      residues in muscle fillet tissues of fish exposed to NIC and TFM during sea
      lamprey control treatments. NIC was extracted from fortified channel catfish and
      rainbow trout fillet tissue with a series of acetone extractions and cleaned up
      on C(18) solid-phase extraction cartridges. NIC concentrations were determined by
      HPLC with detection at 360 and 335 nm for rainbow trout and catfish,
      respectively. Recovery of NIC from rainbow trout (n = 7) fortified at 0.04
      microg/g was 77 +/- 6.5% and from channel catfish (n = 7) fortified at 0.02
      microg/g was 113 +/- 11%. NIC detection limit was 0.0107 microg/g for rainbow
      trout and 0.0063 microg/g for catfish. Percent recovery of incurred radioactive
      residues by this method from catfish exposed to [(14)C]NIC was 89.3 +/- 4.1%.
      Percent recoveries of NIC from fortified storage stability tissue samples for
      rainbow trout (n = 3) analyzed at 5 and 7.5 month periods were 78 +/- 5.1 and 68
      +/- 2.4%, respectively. Percent recoveries of NIC from fortified storage
      stability tissue samples for channel catfish (n = 3) analyzed at 5 and 7.5 month
      periods were 88 +/- 13 and 76 +/- 21%, respectively.

PMID- 10888525
TI  - Front-surface absorbance spectra of wheat flour: determination of carotenoids.
AB  - Front-surface absorbance spectra of wheat flours in the 250-650 nm region can be
      obtained by measuring reflectance spectra with a conventional spectrofluorometer
      suitably set to detect light scattered from powder samples. The spectra recorded
      on flour samples, obtained from seeds of four bread and five durum wheats, show
      high-intensity absorption bands due to aromatic amino acids of wheat proteins and
      low-intensity bands due to chromophores bound to low-molecular-weight compounds.
      The intensity of these last bands is proportional to the concentration of the
      corresponding chromophores present in the flour; thus, it can be used to measure
      the content of the compounds containing the chromophore(s). In particular, a
      quantitative determination of the carotenoids actually present in the flours is
      made, obtaining information on the original content of the seeds. This
      determination is important, as, for example, xanthophylls are well-known
      antioxidants and free-radical scavengers involved in aging processes of seeds.
      Reflectance measurements on powder samples are far more economic in terms of time
      and materials consumption than methods such as extraction and HPLC analysis of
      extracts and, in addition, give an evaluation of the overall content of
      carotenoids with absorption bands in the spectral range 450-500 nm. Application
      of the technique to other food powders with low-intensity absorption bands in the
      near-UV and vis region is possible.

PMID- 10888526
TI  - Evaluation of solid-phase microextraction for the isotopic analysis of volatile
      compounds produced during fermentation by lactic acid bacteria.
AB  - The use of solid-phase microextraction (SPME) coupled with isotope ratio mass
      spectrometry (IRMS) for the analysis of flavor compounds produced by lactic acid
      bacteria has been evaluated using both liquid and headspace sampling modes.
      Initially, it was necessary to optimize the conditions for the SPME extraction of
      flavors-diacetyl and acetoin-in standard aqueous solutions. The effects of salt,
      headspace versus liquid sampling, and coating phase were tested. Second, the
      suitability of the coupling of SPME and gas chromatography-combustion interface
      IRMS (GC-C-IRMS) for the determination of delta(13)C values was assessed. It is
      shown that neither the analyte concentration nor the period of fiber exposure has
      an effect on the delta(13)C values. Finally, having verified that there are no
      matrix effects from the fermentation medium, it is reported for the first time
      that flavor compounds can be extracted directly from culture supernatant by SPME
      and their delta(13)C values can be obtained by GC-C-IRMS.

PMID- 10888527
TI  - Use of phosphonic acid as a generic hapten in the production of broad specificity
      anti-organophosphate pesticide antibody.
AB  - Phosphonic acid (trans-4-phosphono-2-butenic acid; TPB) was used as a generic
      hapten in order to generate broad specificity antibodies against a group of
      organophosphorus pesticides. The polyclonal antiserum showed, in an indirect
      enzyme-linked immunosorbent assay (ELISA) format, preferential binding toward
      pesticides containing unsaturated diethyl-phosphate functionalities rather than
      the equivalent thiophosphate or dimethyl structures. The level of detection in
      the ELISA using a heterologous system was investigated and showed a 20-fold
      improvement when a conjugate for which the antibody had lower affinity was
      immobilized on the plate. Biosensor assays using parathion as a standard
      indicated that the antibody had a relatively high dissociation rate, and
      reproducible cycles of regeneration were achieved. The potential for using TPB as
      a generic hapten is discussed.

PMID- 10888528
TI  - Glucosinolates in members of the family brassicaceae: separation and
      identification by LC/ESI-MS-MS.
AB  - Seeds of 14 different members of the family Brassicaceae were investigated with
      regard to their content and composition of glucosinolates by HPLC-UV/ESI-MS-MS
      coupling. The seeds were extracted with hot methanol/water (70:30 v/v) and the
      desulfoglucosinolates isolated by anion-exchange chromatography with solid-phase
      extraction columns. The desulfoglucosinolates were detected by UV and identified
      by ESI-MS/MS with the neutral loss method. Nineteen different glucosinolates were
      detected in the seeds with a wide range of contents (10-200 micromol/g) and a
      great variation in the composition.

PMID- 10888529
TI  - Determination of whole-body rotenone residues in the brown tree snake (Boiga
      irregularis).
AB  - The brown tree snake (Boiga irregularis) is an introduced pest in Guam,
      responsible for extensive agricultural damage, the extinction of several bird
      species, and severe and frequent electrical power outages. Rotenone, a naturally
      occurring pesticide, has been investigated as a possible chemical control agent.
      An analytical method was developed to assess whole body rotenone residues ranging
      in concentration from 0.035 to 250 microg g(-)(1) in snakes. The method employed
      ethyl acetate extraction of 2 g samples of cryogenically frozen, pulverized
      snakes, followed by silica and Florisil solid-phase extraction cleanup. Extract
      analysis was performed using a high-performance liquid chromatography system
      employing a cyanopropyl analytical column. Tissues fortified to concentrations of
      0.035, 4.82, and 250 microg g(-)(1) yielded analyte recoveries of 85.1, 85.6, and
      83.5%, respectively. The linear response of rotenone standard solutions was
      assessed from 0. 025 to 0.25 microg mL(-)(1) (r(2) = 0.9968) and from 0.250 to
      125 microg mL(-)(1) (r(2) = 0.9999). The method was simple, rugged, and reliable.

PMID- 10888530
TI  - Determination of tetracycline antibiotics in beef and pork tissues using ion
      paired liquid chromatography.
AB  - A simplified procedure was developed for determination of tetracycline
      antibiotics in tissues which improved stability of these compounds in sample
      extracts and eliminated the need for troublesome cleanup procedures. Tissues were
      homogenized in water. Acetonitrile (16 mL) and then 1 mL of 0.1 M H(3)PO(4) were
      added to 4 mL of homogenate and the clear supernatant was filtered. The filtrate
      was mixed with hexane and dichloromethane and the resulting water layer was
      collected, evaporated to 1-2 mL, and filtered into autosampler vials. Ion-pairing
      liquid chromatography was used to separate tetracyclines from interferences in
      sample extracts, eliminating the need for further cleanup. Analysis was isocratic
      using a Phenomonex Prodigy ODS(3) column with a mobile phase of 4 mM oxalic acid,
      4 mM sodium oxalate, 10 mM sodium decanesulfonate-acetonitrile (70 + 30 for
      oxytetracycline and tetracycline; 66 + 34 for chlortetracycline). Recoveries were
      generally in the 90-100% range with limits of quantitation of 0. 05-0.1 ppm. The
      procedure was evaluated with beef and pork muscle, liver, and kidney.

PMID- 10888531
TI  - Reliability of analytical methods for determining anthocyanins in blood orange
      juices.
AB  - Quantitative analysis of anthocyanins was performed on a series of blood orange
      juices according to various spectrophotometric and HPLC methods, and the causes
      for different concentration resulting from the application of such procedures
      were investigated. Spectrophotometric methods utilizing aqueous ethanol as a
      solvent provided an anthocyanin content higher than that determined by HPLC.
      Discrepancies were ascribed to the use of impure standards and/or unsuitable
      calibration lines. The most consistent results with the HPLC findings were
      obtained by a method utilizing water as a solvent and cyanidin-3-glucoside as a
      standard. Actual concentration of anthocyanins in blood orange juice was
      remarkably lower than that currently determined by procedures used in the juice
      producing factories.

PMID- 10888532
TI  - Solid phase microextraction/gas chromatography of Salmonella-infected beef.
AB  - Eight strains of Salmonellae were incubated in TSB culture medium at 37 degrees C
      for 24 h. Volatile compounds derived from the bacteria were collected using solid
      phase microextraction fibers and then applied to gas chromatography (GC).
      Similarity analysis of the GC patterns thus obtained could separate these strains
      on principal component similarity (PCS) scattergrams. Five major food-related
      pathogenic bacteria and 10 other bacteria (including one Salmonella strain) were
      also classified by growing in the same medium. It is then proposed to utilize
      this approach to improve the GC/PCS method of Nakai et al. [Nakai, S.; Wang, Z.
      H.; Dou, J.; Nakamura, S.; Ogawa, M.; Nakai, E.; Vangerstoep, J. J. Agric. Food
      Chem. 1999, 47, 576-583] that has been developed for screening safe foods by
      detecting bacteria contaminated foods. Inoculating food samples pre-enriched
      through preliminary incubation into a culture medium and then subjecting to the
      GC/PCS method after secondary incubation enhances the detectability of pathogenic
      bacteria.

PMID- 10888533
TI  - Effect of water content on dielectric relaxation of gelatin in a glassy state.
AB  - The dielectric properties of gelatin in the glassy state were measured from 100
      Hz to 1 MHz over a temperature range of -20 to 60 degrees C. Samples with
      different water contents were prepared by varying the drying time for desalted
      gelatin solution; they were confirmed to be in the glassy state from DSC
      measurements. The dielectric relaxation (the decrease in dielectric constant,
      epsilon', and the maximum of the dielectric loss, epsilon' ') was observed for
      each sample; the relaxation time tau was evaluated from the peak of epsilon' '.
      The activation energy E obtained from an Arrhenius plot of tau decreased with
      increasing water content. On the basis of the order of magnitude of E, the
      dielectric relaxation observed was considered to be beta-relaxation reflecting
      the local motion of molecules. E and tau seem to describe the enhancement effect
      of water on the mobility of gelatin molecules in the glassy state; tau and E are
      considered to be suitable parameters for the characterization of the plasticizing
      effect of water on a glassy material.

PMID- 10888534
TI  - Individual and combined antioxidant effects of seven phenolic agents in human
      erythrocyte membrane ghosts and phosphatidylcholine liposome systems: importance
      of the partition coefficient.
AB  - Antioxidant activities of seven phenolic agents against Fe(2+)-induced lipid
      oxidation were compared with alpha-tocopherol, beta-carotene, and vitamin C in
      human erythrocyte membrane ghosts and liposome systems. The antioxidant activity
      of five test flavonoids followed the order catechin > epicatechin > rutin >
      quercetin > myricetin in both systems (p < 0.05), which was negatively correlated
      with their partition coefficients. The antioxidant interaction of these phenolic
      agents with alpha-tocopherol, beta-carotene, or vitamin C in inhibiting Fe(2+)
      induced lipid oxidation was examined. Synergistic effects were present in the
      combinations of alpha-tocopherol plus caffeic acid, catechin, or epicatechin as
      well as in all combinations of vitamin C plus phenolic antioxidants. On the basis
      of the stronger individual and combined effects present in caffeic acid,
      catechin, and epicatechin, the application of these three phenolic agents with or
      without alpha-tocopherol, beta-carotene, and vitamin C may provide stronger
      protective benefits against lipid oxidation, which may be helpful for oxidation
      related diseases prevention.

PMID- 10888535
TI  - Mutagenicity of heated sugar-casein systems: effect of the Maillard reaction.
AB  - The formation of mutagens after the heating of sugar-casein model systems at 120
      degrees C was examined by the Ames test, using Salmonella typhimurium strain
      TA100. Several sugars (glucose, fructose, galactose, tagatose, lactose, and
      lactulose) were compared in their mutagenicities. Mutagenicity could be fully
      ascribed to Maillard reaction products and strongly varied with the kind of
      sugar. The differences in mutagenicity among the sugar-casein systems were caused
      by a difference in reaction rate and a difference in reaction mechanism. Sugars
      with a comparable reaction mechanism (glucose and galactose) showed a higher
      mutagenic activity corresponding with a higher Maillard reactivity. Disaccharides
      showed no mutagenic activity (lactose) or a lower mutagenic activity (lactulose)
      than their corresponding monosaccharides. Ketose sugars (fructose and tagatose)
      showed a remarkably higher mutagenicity compared with their aldose isomers
      (glucose and galactose), which was due to a difference in reaction mechanism.

PMID- 10888536
TI  - Gallic acid metabolites are markers of black tea intake in humans.
AB  - Gallic acid is one of the main phenolic components of black tea. The objective of
      this study was to identify urinary gallic acid metabolites with potential for use
      as markers of black tea intake. In an initial study, nine compounds, assessed by
      using gas chromatography-mass spectrometry, were found to increase in
      concentration in urine after 3 cups of black tea over 3 h. A subsequent study
      employed a controlled crossover design in which 10 subjects consumed 5 cups per
      day of black tea or water for 4 weeks in random order. Twenty-four hour urine
      samples were collected at the end of each period. Of the 9 candidate compounds
      identified in the initial study, only 3 were present at higher concentrations in
      urine of all 10 subjects during tea-drinking in comparison to water-drinking
      periods. These compounds were identified as 4-O-methylgallic acid, 3-O
      methylgallic acid, and 3, 4-O-dimethylgallic acid, all methyl ether derivatives
      of gallic acid. It is suggested that these compounds have the potential to be
      used as markers of black tea intake.

PMID- 10888537
TI  - Strains of lactic acid bacteria isolated from sour doughs degrade phytic acid and
      improve calcium and magnesium solubility from whole wheat flour.
AB  - Five strains of lactic bacteria have been isolated from sour doughs and examined
      for their ability to degrade phytic acid. In white flour medium in which phytic
      acid was the only source of phosphorus, the disappearance of phytate and an
      elevation of inorganic phosphate were observed after only 2 h of incubation in
      all strains tested (-30 and +60%, respectively). Both phenomena correspond to
      phytate breakdown. No difference was observed in the levels of phytic acid
      hydrolysis among strains, suggesting that phytase enzymes are similar among these
      bacteria. Using whole wheat flour medium naturally rich in phytic acid in the
      presence of Leuconostoc mesenteroides strain 38, a 9 h fermentation established
      that the degradation of PA and the production of lactic acid lead to greater Ca
      and Mg solubility than in control medium.

PMID- 10888538
TI  - Nutritional assessment in vitro and in vivo of raw and extruded peas (Pisum
      sativum L.).
AB  - The effects of extrusion cooking on the nutritional properties of Pisum sativum
      L. have been evaluated in vitro and in vivo. The treatment greatly elevated
      protein and starch digestibility in vitro. Also, the amounts of intact starch
      diminished while total free sugars increased. In addition, the levels of
      antinutritional factors, such as protease inhibitors and lectins, were greatly
      decreased. Concentrations of methionine and cystine were low in raw peas and were
      further reduced by extrusion treatment. The nutritional performance of rats fed
      extruded pea diets for 15 days was no better than that of rats given raw pea
      diet. This was due to the overriding effects of amino acid deficiencies in the
      diets. Weight gains by rats fed extruded pea diets supplemented with amino acids
      were, however, much higher than those achieved by rats fed supplemented raw pea
      diets. Food transformation index and protein efficiency ratio values were also
      greatly improved. Extrusion treatment did therefore significantly improve the
      nutritional quality of peas.

PMID- 10888539
TI  - Waste water from citrus processing as a source of hesperidin by concentration on
      styrene-divinylbenzene resin.
AB  - This paper describes a procedure for recovering hesperidin from the waste water
      of orange juice processing, namely, yellow water, by concentration of diluted
      extracts on styrene-divinylbenzene resin. Turbid raw material flowing out from
      centrifuges of essential oil separation contains considerable amount of
      hesperidin ( approximately 1 g/L) mainly associated with solid particles. Yellow
      water was treated with calcium hydroxide until pH 12 to solubilize hesperidin,
      filtered, neutralized at pH 6, and loaded on resin up to saturation. Desorption
      with 10% ethanol aqueous solutions at different NaOH concentrations (0.23-0.92 M)
      assured high concentration of hesperidin in selected fractions (10-78 g/L), from
      which it precipitated in high yield and purity immediately after acidification at
      pH 5. Best results were obtained using 0.46 M NaOH as eluent: 71.5% of the
      adsorbed hesperidin was desorbed in 300 mL, with an overall 64% yield of isolated
      product at 95.4% purity (HPLC). These experiments can constitute a useful
      starting point for an industrial application.

PMID- 10888540
TI  - One- and two-dimensional gel electrophoresic identification of African yam bean
      seed proteins.
AB  - Seed proteins were extracted from the African yam bean (AYB; Sphenostylis
      stenocarpa), an underutilized West African food legume. One- and two-dimensional
      polyacrylamide gel electrophoresis was then used to analyze the albumin fraction,
      galactose-specific lectins purified on immobilized galactose-Sepharose 4B, and
      abundant non-lectin seed proteins left over following affinity chromatography. N
      terminal sequencing of prominently resolved polypetide bands led to
      identification of proteins having sequence homology with characterized legume
      seed proteins, namely, mung bean seed albumin, pea alpha-fucosidase, soybean
      Kunitz-type trypsin inhibitor, an endochitinase, pea pathogenesis-related
      protein, and/or cowpea seed storage proteins. Minor lectin-like proteins lacking
      hemagglutinating activity against rabbit and human erythrocytes were also
      identified. Because proteins such as protease inhibitors, chitinases,
      pathogenesis-related proteins, and lectins are known to have antimetabolic
      effects, the findings from this study may have relevance in the acceptability,
      adoption, and utilization of AYB as human food.

PMID- 10888541
TI  - Heavy metals in Egyptian spices and medicinal plants and the effect of processing
      on their levels.
AB  - To determine the contamination of Egyptian spices and medicinal plants with heavy
      metals, a total of 303 samples, which represent 20 different types of spices and
      medicinal plants that were collected from areas of exportation in Egypt, were
      analyzed for heavy metals. Some of them have different growing seasons, and each
      has its own agricultural practices and several shipments. The results revealed
      that heavy metal contents in spice and medicinal plants depend on the plant
      species. The maximum levels of heavy metals in the analyzed samples were 14.4,
      2.44, 33.75, 2.85, 0.10, 68.80, 343.0, 11.40, and 1046.25 microg/g for Pb, Cd,
      Cr, Ni, Sn, Zn, Mn, Cu, and Fe, respectively. Cobalt was not detected in any of
      the various samples under investigation. The levels of heavy metals determined in
      the analyzed samples were found to exceed the maximum allowable levels of
      Zentrale Erfassungs und Bewertungsstelle fur Umweltchemikalien. The investigated
      medicinal plants were also processed by two different methods to determine the
      behavior of their metal contents during processing. It has been found that
      boiling the plant in water leads to the extraction of higher amounts of the metal
      from the plant than immersing it in the hot water. The achieved results were
      tabulated.

PMID- 10888542
TI  - Glyphosate-tolerant corn: the composition and feeding value of grain from
      glyphosate-tolerant corn is equivalent to that of conventional corn (Zea mays
      L.).
AB  - Glyphosate-tolerant (Roundup Ready) corn line GA21 has been developed by genetic
      modification to tolerate glyphosate, the active ingredient in Roundup herbicide.
      The purpose of this study was to evaluate the compositional and nutritional
      safety of corn line GA21 compared to that of conventional corn. Compositional
      analyses were conducted to measure proximate, fiber, amino acid, fatty acid, and
      mineral contents of grain and proximate, fiber, and mineral contents of forage
      collected from 16 field sites over two growing seasons. The nutritional safety of
      corn line GA21 was evaluated in a poultry feeding study conducted with 2-day old,
      rapidly growing broiler chickens, at a dietary concentration of 50-60% w/w.
      Compositional analysis results showed that, except for a few minor differences
      that are unlikely to be of biological significance, the grain and forage of GA21
      corn were comparable in their composition to that of the control corn line and to
      conventional corn. Results from the poultry feeding study showed that there were
      no differences in growth, feed efficiency, adjusted feed efficiency, and fat pad
      weights between chickens fed with GA21 grain or with parental control grain.
      These data taken together demonstrate that Roundup Ready corn is as safe and
      nutritious as conventional corn for food and feed use.

PMID- 10888543
TI  - Triterpene alcohol and sterol ferulates from rice bran and their anti
      inflammatory effects.
AB  - Six novel feruloyl esters of triterpene alcohols and sterols, viz., two trans
      ferulates, cycloeucalenol and 24-methylenecholesterol trans-ferulates, and four
      cis-ferulates, cycloartenol, 24-methyelenecycloartanol, 24-methylcholesterol, and
      sitosterol cis-ferulates, besides five known trans-ferulates, cycloartenol (CAR),
      24-methylenecycloartanol (24-MCA), 24-methylcholesterol, sitosterol, and
      stigmastanol trans-ferulates, and one known cis-ferulate, stigmastanol cis
      ferulate, were isolated from the methanol extract of edible rice bran. These and
      eight other synthetic trans- and cis-ferulates of triterpene alcohols and
      sterols, along with the corresponding free alcohols, were evaluated with respect
      to their anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate
      (TPA)-induced inflammation (1 microg per ear) in mice. All of the ferulates
      showed marked inhibitory activity, and their 50% inhibitory dose (ID(50)) was 0.
      1-0.8 mg per ear. On the other hand, whereas two free triterpene alcohols, CAR
      and 24-MCA, showed strong inhibition (ID(50) 0.2-0.3 mg/ear), eight free sterols
      examined showed weaker activity (ID(50) 0.7-2.7 mg/ear) than their corresponding
      ferulates.

PMID- 10888544
TI  - Free radical scavenging activity and antiulcer activity of garcinol from Garcinia
      indica fruit rind.
AB  - Garcinol, a polyisoprenylated benzophenone derivative, was purified from Garcinia
      indica fruit rind, and its free radical scavenging activity was studied using
      electron spin resonance (ESR) spectrometry. In the hypoxanthine/xanthine oxidase
      system, emulsified garcinol suppressed superoxide anion to almost the same extent
      as DL-alpha-tocopherol by weight. In the Fenton reaction system, garcinol also
      suppressed hydroxyl radical more strongly than DL-alpha-tocopherol. In the
      H(2)O(2)/NaOH/DMSO system, garcinol suppressed superoxide anion, hydroxyl
      radical, and methyl radical. It was thus confirmed that this derivative is a
      potent free radical scavenger and able to scavenge both hydrophilic and
      hydrophobic ones including reactive oxygen species. Orally administered garcinol
      prevented acute ulceration in rats induced by indomethacin and water immersion
      stress caused by radical formation. These results suggested garcinol might have
      potential as a free radical scavenger and clinical application as an antiulcer
      drug.

PMID- 10888545
TI  - Lignin structure in a mutant pine deficient in cinnamyl alcohol dehydrogenase.
AB  - Cinnamyl alcohol dehydrogenase (CAD) activity is deficient in loblolly pine
      (Pinus taeda L.) harboring a mutated allele of the cad gene (cad-n1). We compared
      lignin structure of CAD-deficient and wild-type pines, both types segregating
      within full-sib families obtained by controlled crosses. The type and frequency
      of lignin building units and distribution of interunit bonds were determined from
      the GC-MS analysis of thioacidolysis monomers and dimers. While the lignin
      content was only slightly reduced, the lignin structure was dramatically modified
      by the mutation in both mature and juvenile trees. Lignins from CAD-deficient
      pine displayed unusually high levels of coniferaldehyde and dihydroconiferyl
      alcohol. In addition, biphenyl and biphenyl ether bonds were in large excess in
      these abnormal lignins. These results suggest that the CAD-deficient pines
      efficiently compensate for the shortage in normal lignin precursors by utilizing
      nontraditional wall phenolics to construct unusual lignins particularly enriched
      in resistant interunit bonds.

PMID- 10888546
TI  - Effects of pulsed electric fields on ovalbumin solutions and dialyzed egg white.
AB  - Ovalbumin solutions (2%, pH 7.0, 200 ohm.cm) and dialyzed fresh egg white (pH
      9.2, 200-250 ohm.cm) were subjected to 50-400 exponential decay pulses with an
      electric field strength of 27-33 kV/cm. The pulse width was ca. 0.3 micros (at a
      capacitance of 20 nF) or 0.9 micros (at 80 nF), and the corresponding dissipated
      energy was 0.7 or 2.3 J/(pulse.mL) of solution. The sample temperature was
      maintained below 29 degrees C. While the four sulfhydryl groups of native
      ovalbumin did not react with DTNB, they became reactive immediately after pulse
      processing, indicating either partial protein unfolding or enhanced SH
      ionization. The extent of SH reactivity increased with dissipated energy, 3.7 SH
      groups becoming reactive after 100 or 200 pulses at 31.5 kV/cm and 80 nF.
      However, SH reactivity was reversible, since only 0.79 or 0.2 SH group was found
      to remain reactive 30 min or 8 h after pulse processing. The fourth derivatives
      of UV spectra of ovalbumin were determined, before and 15-30 min after pulse
      processing, to assess possible polarity and conformation changes in the
      environment of tyrosine and tryptophan. No differences were observed. Thermal
      gels prepared from fresh or dialyzed egg white had markedly different mechanical
      and water retention characteristics. Pulse processing of dialyzed egg white (200
      pulses, 30 kV/cm, 80 nF) only slightly reduced its gelling properties. Thus
      electric pulses known to induce significant microbial inactivation did not cause
      notable changes in the proteins investigated.

PMID- 10888547
TI  - Influence of storage conditions on the formation of some volatile compounds in
      white fortified wines (Vins doux naturels) during the aging process.
AB  - Sweet fortified wines, traditionally aged under strong oxidation conditions, have
      a characteristic aroma. An experimental study investigated the aging of white
      sweet fortified wines under various conditions. The development of various
      molecules, previously identified as characteristic of the aroma of this type of
      wine, was monitored by analysis. The development of these compounds during
      accelerated aging was affected by oxidation and the color of the wine. Aging in
      oak containers, variable storage temperatures, and variable modes of oxidation
      affect the formation of many of the volatile compounds responsible for the aging
      aroma of vins doux naturels (fortified wines). Furfural (1), 5
      ethoxymethylfurfural (2), and sotolon (3) always reach concentrations above their
      perception thresholds in wood-aged wines, especially when new oak is used. The
      isomers of methyl-gamma-octalactone (4 and 5) are reliable indicators of aging in
      oak. Among the many identifiable volatile phenols, only the vanillin (7) content
      increases with aging, particularly if the container is made of wood and there is
      a high degree of oxidation. This molecule frequently reaches and even exceeds its
      perception threshold. We show here that vanillin and isomers of methyl-gamma
      octalactone have a major impact on the aromas of fortified wines.

PMID- 10888548
TI  - Properties of herbage in relation to equine dysautonomia: biochemical composition
      and antioxidant and prooxidant actions.
AB  - To investigate the etiology of equine dysautonomia (ED), a degenerative
      polyneuropathy affecting grazing horses, the biochemical composition and
      antioxidant/prooxidant activities of aqueous extracts of plants collected from ED
      pastures were determined. Plants collected immediately after an outbreak of ED
      had reduced antioxidant and weak prooxidant activities when compared with control
      plants (plants collected from ED pastures out of ED season and control plants
      from ED pastures that were grown under favorable conditions). ED plants also had
      significantly increased concentrations of fructose and low molecular weight
      phenolic compounds, significantly more of one amino acid zone (probably valine),
      significantly less tartaric acid, and a nonsignificant decrease in ascorbic acid
      content when compared with control plants from ED pastures that were grown under
      favorable conditions. These findings suggest that ED plants may be under
      oxidative stress, possibly due to chilling, drought, or fungal colonization.
      However, experimental drought and chilling of plants did not reproduce the
      biochemical alterations identified in ED plants. It is possible that the altered
      biochemical content of ingested plants may contribute, directly or indirectly, to
      the development of ED in grazing horses.

PMID- 10888549
TI  - Application of an electronic nose to predict total volatile bases in capelin
      (Mallotus villosus) for fishmeal production.
AB  - An electronic nose was used as a rapid technique to monitor changes in the
      headspace gas above capelin (Mallotus villosus) during storage at 0 and 5 degrees
      C. At both temperatures, refrigeration was compared with an ice/seawater cooling
      system. At 5 degrees C, the effect of added 0.2% acetic acid was also tested.
      Electronic nose measurements were compared to measurements of total volatile
      bases (TVB), gas chromatography of volatile compounds, and sensory analysis. TVB
      analysis indicated less spoilage in seawater/ice systems than in refrigeration,
      but the other measurements indicated more spoilage in the seawater system
      compared to refrigeration. The possibility of using only a few sensors in the
      electronic nose to predict TVB was studied using partial least squares regression
      and a saturated generalized linear model. The results reported herein indicate
      that rapid electronic nose measurements, which require no sample preparation, can
      be used to predict the TVB value of the raw material stored under different
      conditions.

PMID- 10888550
TI  - Headspace solid-phase microextraction use for the characterization of volatile
      compounds in vegetable oils of different sensory quality.
AB  - Headspace solid-phase microextraction (HS-SPME) was used to isolate the volatile
      compounds, which are formed during peroxidation of fatty acids in vegetable oils.
      Isolated compounds were characterized by GC-MS and quantified using GC with FID
      detection. Four fibers for HS-SPME method development were tested, and the
      divinylbenzene/carboxene/PDMS fiber was selected as providing the best detection
      of analyzed compounds. Extraction curves, limits of detection, repeatability, and
      linearity were investigated for 14 aldehydes, ketones, hydrocarbons, and alcohols
      being products of fatty acids autoxidation. Limits of detection for 11 of these
      were below 1 microg/L. For quantitative purposes, to minimize the influence of
      temperature on hydroperoxide formation and the changes in the volatiles profile
      of the extracts, sampling was performed at 20 degrees C. For compound
      characterization by GC-MS, sampling temperature of 50 degrees C was applied. The
      developed method was applied to the analysis of refined and cold-pressed rapeseed
      oil stored at 60 degrees C for 10 days, and for 10 different vegetable oils of
      various degree of peroxidation. All samples were subjected to sensory analysis.
      The results of PCA sensory analysis were related to the amount of volatile
      compounds isolated by SPME method. In cases where the amount of compounds was
      highest, the samples were perceived as the worst, whereas those with low levels
      of volatile compounds were the most desired ones according to sensory evaluation.
      The relation was observed for both total volatiles, quantified C5-C9 aldehydes,
      and 14 compounds selected in method development. SPME revealed to be a rapid and
      sensitive method for the extraction and quantitation of trace volatile compounds
      from plant oils even at ambient temperature.

PMID- 10888551
TI  - Effects of the sniffing port air makeup in gas chromatography-olfactometry.
AB  - A time-intensity gas chromatography-olfactometry (GCO) apparatus was developed to
      study some aerodynamic parameters that may influence odor detection and intensity
      measurements by the subjects. The addition of humidified air at the elution place
      of the compounds is generally recommended for several reasons (essentially to
      prevent nasal mucosa dehydration and to improve chromatographic effluent carriage
      out of the column), but clues about these effects are yet to be published. This
      question is studied through two complementary experiments using synthetic
      solutions of 3-methyl-1-butanethiol, hexan-2-one, octanal, nonanal, furfural,
      citronellal, benzaldehyde, octan-1-ol, 2-phenylethyl acetate, guaiacol, 2
      phenylethanol, and vanillin. This work demonstrates the need for an air makeup to
      increase odor detection frequency and intensity rating. With the conditions
      tested, a minimum makeup air flow rate of 50 L.min(-)(1) is necessary. On the
      contrary, humidification of the makeup is useless for the sniffers comfort and to
      improve the quantitative GCO results.

PMID- 10888552
TI  - Study of interaction phenomena between aroma compounds and carbohydrate matrixes
      by inverse gas chromatography.
AB  - Besides the conventional techniques used for the investigation of food-flavor
      interactions, inverse gas chromatography (IGC) may provide a useful tool for the
      direct assessment of the retention of aroma compounds in a matrix. IGC consists
      of single reference compound injections at a fixed temperature onto a column
      which stationary phase is the material of interest. We have applied this
      technique to high amylose corn starch, wheat starch, and beta-cyclodextrin
      matrixes, using aroma compounds presenting various functional groups. Low energy
      interactions were measured which may result from polar or hydrophobic binding.
      Starch behaved under these conditions as a polar chromatographic phase. We also
      focused on the influence of a physical modification of the starch on its
      retention properties toward 3,7-dimethyl-2,6-octadien-1-al. Retention was found
      to be greater after a specific thermal treatment. As checked by DSC (differential
      scanning calorimetry) and DMTA (dynamic mechanical and thermal analysis), the
      observed changes are believed to be related to the glass transition of the
      starch. For the time being, the dehydration of the matrix associated with the
      lack of control of the relative humidity within the column is the main
      restriction to this technique.

PMID- 10888553
TI  - Olfactory and quantitative analysis of aroma compounds in elder flower (Sambucus
      nigra L.) drink processed from five cultivars.
AB  - Fresh elder flowers (Sambucus nigra L.) were extracted with an aqueous solution
      containing sucrose, peeled lemon slices, tartaric acid, and sodium benzoate to
      make elder flower syrup. Aroma compounds emitted from the elder flower syrup were
      collected by the dynamic headspace technique and analyzed by GC-FID and GC-MS. A
      total of 59 compounds were identified, 18 of which have not previously been
      detected in elder flower products. The concentrations of the identified volatiles
      were measured in five elder cultivars, Allesoe, Donau, Sambu, Sampo, and Samyl,
      and significant differences were detected among cultivars in the concentration
      levels of 48 compounds. The odor of the volatiles was evaluated by the GC
      sniffing technique. cis-Rose oxide, nerol oxide, hotrienol, and nonanal
      contributed to the characteristic elder flower odor, whereas linalool, alpha
      terpineol, 4-methyl-3-penten-2-one, and (Z)-beta-ocimene contributed with floral
      notes. Fruity odors were associated with pentanal, heptanal, and beta
      damascenone. Fresh and grassy odors were primarily correlated with hexanal,
      hexanol, and (Z)-3-hexenol.

PMID- 10888554
TI  - Evidence of Strecker aldehyde excretion by yeast in cold contact fermentations.
AB  - A medium containing labeled leucine-d(10) has been used to show that
      Saccharomyces cerevisiae was able to produce deuterated 3-methylbutanal in a cold
      contact fermentation. Whereas residual unreduced Strecker aldehydes bound to
      polyphenols were considered until now as the main defect of alcohol-free beers,
      yeast emerges from this work as an additional source of worty flavor. When the
      same experiment was conducted without leucine, 3-methylbutanal excretion also
      occurred, indicating that valine could be used by yeast as precursor.

PMID- 10888555
TI  - Occurrence of 12-methyltridecanal in microorganisms and physiological samples
      isolated from beef.
AB  - 12-Methyltridecanal (MT) smelling tallowy, beef-like was formed from plasmalogens
      when beef was boiled. To clarify the origin of MT, its concentration was
      determined by a stable isotope dilution assay in bacteria and protozoa isolated
      from the rumen of bovine animals as well as in the plasma, erythrocytes, and
      other physiological samples. The highest amounts of MT were found in bacteria
      followed by protozoa. The MT content of the erythrocytes was small. The results
      support the hypothesis that microorganisms are the main source of MT of which a
      small amount is resorbed by the animal and transported to the muscular tissue
      where MT is incorporated into plasmalogens.

PMID- 10888556
TI  - Studies on the key odorants formed by roasting of wild mango seeds (Irvingia
      gabonensis).
AB  - Application of the aroma extract dilution analysis on a concentrate of volatiles
      obtained by solvent extraction and high vacuum distillation from roasted seeds
      (180 degrees C; 15 min) of wild mango (Irvingia gabonensis) revealed 32 odor
      active compounds with flavor dilution (FD) factors ranging from 8 (low odor
      activity) to 2048 (high odor activity). The identification experiments based on
      the use of reference odorants revealed methional (cooked potato-like) followed by
      2-acetyl-1-pyrroline (roasty, popcorn-like), butan-2,3-dione, pentan-2,3-dione, 2
      ethyl-3,5-dimethylpyrazine, and 2,3-diethyl-5-methylpyrazine as the key aroma
      compounds among the 27 odorants identified. All odorants are reported for the
      first time as components of roasted wild mango seeds.

PMID- 10888557
TI  - Influence of the simultaneous addition of the protease flavourzyme and the lipase
      novozym 677BG on dry fermented sausage compounds extracted by SDE and analyzed by
      GC-MS.
AB  - A dry fermented sausage (chorizo de Pamplona) was elaborated with the
      simultaneous addition of a lipase (Novozym 677BG) and a protease (Flavourzyme)
      and ripened during 21 days, in contrast to the control without enzymes and
      ripened during 35 days. Faster and more intense lipolytic and proteolytic
      activities were observed in the modified sausage, despite its shorter maturation
      time. At the end of the ripening, a determination of the profile of compounds
      extracted by simultaneous distillation-extraction with dichloromethane was
      carried out. The total amounts of extracted compounds (expressed in milligrams of
      dodecane per gram of dry matter) were 2.5 in the sausage with enzymes and 1.9 in
      the control. The chemical groups showing increments due to the use of enzymes
      were esters (103.5% increment) and acids (87% increment) in both cases due to the
      greater presence of long-chain fatty acid products. However, development of
      substances originated from further degradation process of amino acids and free
      fatty acids did not seem to have taken place.

PMID- 10888558
TI  - Effects of hexanal, trans-2-hexenal, and storage temperature on shelf life of
      fresh sliced apples.
AB  - In this paper, the effects of hexanal and trans-2-hexenal, which are both natural
      molecules characterizing apple aroma, on the microbial population and on color
      retention of fresh sliced apples were evaluated. In particular, a central
      composite design (CCD) was developed to assess the individual and interactive
      effects of the chosen volatile molecules and storage temperatures on (i) the
      growth of the naturally occurring microflora, (ii) the evolution over time of an
      inoculated spoilage yeast (Pichia subpelliculosa), and (iii) the enzymatic
      browning reaction in minimally processed apples. The inclusion of hexanal and
      trans-2-hexenal in the storage atmosphere of apple slices determined a
      significant extension of shelf life also when P. subpelliculosa was inoculated at
      levels of 10(3) colony-forming units/g and abusive storage temperatures were
      used. In fact, the presence of these molecules in the packaging atmospheres
      considerably prolonged the lag phases of the inoculated yeast and reduced the
      growth potential of naturally occurring bacteria. Moreover, the addition to the
      modified atmosphere of low levels of the hexanal increased the color stability of
      the products up to 16 days.

PMID- 10888559
TI  - Composition of essential oil of costmary [Balsamita major (L.) Desf. ] at
      different growth phases.
AB  - The essential oils from leaves and flowers of costmary, Balsamita major (L.)
      Desf. (syn. Chrysanthemum balsamita L.), were analyzed at various phases of plant
      growth. The highest contents of oil both in leaves and in flowers were determined
      before full blooming, 1.15 and 1.34% (w/w), respectively. Seventy-eight volatile
      compounds have been identified in the oils of Balsamita major, of which 58 (19
      tentatively, 39 positively) have not been reported in this plant previously.
      Carvone and alpha-thujone were found to be dominating compounds constituting from
      51.8 to 68.0% and from 9.0 to 16.1% in the total oil, respectively. Seasonal
      variations in the oil compositions were not considerable except for the starting
      phase (May 25, 1995), when the content of carvone was lower and the content of
      alpha-thujone and sesquiterpenes higher. The content of sesquiterpenes was
      approximately 2 times higher in flowers than in the leaves. Absolute amount of
      most components was highest at the bud formation period.

PMID- 10888560
TI  - Origin of carbohydrate degradation products in L-Alanine/D-[(13)C]glucose model
      systems.
AB  - Maillard model systems consisting of labeled D-[(13)C]glucoses and L
      [(13)C]alanines have been utilized to identify the origin of carbon atoms in
      glycolaldehyde, pyruvaldehyde, 1-hydroxy-2-propanone (acetol), 2,3-butanedione, 3
      hydroxy-2-butanone, 2,3-pentanedione, and compounds containing C(5) and C(6)
      intact glucose carbon chains. The origin of carbon atoms in glycolaldehyde and
      pyruvaldehyde was inferred from the analysis of label incorporation pattern of
      methyl and dimethylpyrazines. The origin of carbon atoms in the remaining
      compounds was determined by direct analysis. The data indicated that
      glycolaldehyde incorporated intact C5-C6 and C1-C2 carbon chains of glucose.
      Acetol and pyruvaldehyde incorporated intact C1-C2-C3 and C4-C5-C6 carbon chains
      of glucose. On the other hand, 2, 3-butanedione and 3-hydroxy-2-butanone
      incorporated intact C3-C4-C5-C6 carbon chain of glucose. In addition, analysis of
      compounds containing intact glucose C(5) carbon chains have indicated that
      glucose in the presence of L-alanine can lose either C-1 atom to produce a
      pentitol moiety responsible for the formation of furanmethanol or it can lose the
      C-6 atom to produce a pentose moiety responsible for the formation of furfural.
      Plausible mechanisms, consistent with the observed label incorporation, were
      proposed for the formation of sugar degradation products.

PMID- 10888561
TI  - Formation of 2-alkyl-(2H)-thiapyrans and 2-alkylthiophenes in cooked beef and
      lamb.
AB  - 2-Alkyl-(2H)-thiapyrans and 2-alkylthiophenes have been identified in the
      volatiles of cooked beef and lamb. The quantities of both groups of compounds
      were higher in the meat of animals fed lipid supplements high in n-3
      polyunsaturated fatty acids. 2-Alkyl-(2H)-thiapyrans were formed when (E,E)-2,4
      dienals (C(6)-C(11)) and hydrogen sulfide were heated at 140 degrees C for 30
      min. This confirmed their proposed route of formation in cooked meat from lipid
      derived aldehydes and hydrogen sulfide; the latter was produced from the
      degradation of cysteine, via the Maillard reaction. The mass spectra and NMR
      spectra of these thiapyrans are reported for the first time. Although 2-alkyl
      (2H)-thiapyrans were found to have only low odor potency, the reactions by which
      they are formed may have important implications for meat flavor. These reactions
      may remove potent aroma compounds and their intermediates from meat, thus
      modifying the overall aroma profile.

PMID- 10888562
TI  - Volatile constituents in fresh and processed juices from grapefruit and new
      grapefruit hybrids.
AB  - Forty-five volatile constituents of juices from grapefruit and grapefruit hybrids
      were quantified by headspace gas chromatography. The three types of grapefruit
      juice analyzed include pasteurized juice not from concentrate, reconstituted
      single strength juice from concentrate, and fresh, unpasteurized juice. Principal
      component and discriminant analyses were carried out using 48 grapefruit juice
      samples, and the samples were classified into the three types of juice based on
      degree of processing. Discriminant analysis was superior to principal component
      analysis for this purpose. Juices from two recently developed grapefruit hybrids
      were classified similarly to unpasteurized grapefruit juices from commercial
      cultivars.

PMID- 10888563
TI  - Solid-phase microextraction method development for headspace analysis of volatile
      flavor compounds.
AB  - Solid-phase microextraction (SPME) fibers were evaluated for their ability to
      adsorb volatile flavor compounds under various conditions with coffee and aqueous
      flavored solutions. Experiments comparing different fibers showed that
      poly(dimethylsiloxane)/divinylbenzene had the highest overall sensitivity.
      Carboxen/poly(dimethylsiloxane) was the most sensitive to small molecules and
      acids. As the concentrations of compounds increased, the quantitative linear
      range was exceeded as shown by competition effects with 2-isobutyl-3
      methoxypyrazine at concentrations above 1 ppm. A method based on a short-time
      sampling of the headspace (1 min) was shown to better represent the equilibrium
      headspace concentration. Analysis of coffee brew with a 1-min headspace
      adsorption time was verified to be within the linear range for most compounds and
      thus appropriate for relative headspace quantification. Absolute quantification
      of volatiles, using isotope dilution assays (IDA), is not subject to biases
      caused by excess compound concentrations or complex matrices. The degradation of
      coffee aroma volatiles during storage was followed by relative headspace
      measurements and absolute quantifications. Both methods gave similar values for 3
      methylbutanal, 4-ethylguaiacol, and 2,3-pentanedione. Acetic acid, however, gave
      higher values during storage upon relative headspace measurements due to
      concurrent pH decreases that were not seen with IDA.

PMID- 10888564
TI  - Volatile compounds produced from monosodium glutamate in common food cooking.
AB  - A mixture of soybean oil and/or water, sugar and/or monosodium glutamate (MSG)
      was water-boiled or oil-heated at 100, 120, 140, 160, or 170 degrees C,
      respectively, and volatile compounds produced were isolated by solid-phase
      microextraction and then identified by GC and GC/MS. Oxidative thermal
      degradation products of fatty acids (OTDPFA) were the major volatile compounds
      detected for all water-boiled samples. When MSG and sugar were heated together,
      2, 5-dimethyl pyrazine and methyl pyrazine were also detected at or after 160 min
      heating. Water added in soybean oil increased OTDPFA production. In oil-heated
      samples of soybean oil alone, soybean oil with MSG, and soybean oil with sugar,
      OTDPFA were also the major compounds found. The samples containing MSG also
      produced 2-pyrrolidone, and the samples containing sugar also produced furfural
      and 5-hydroxy methyl furfural. The samples containing soybean oil, sugar, and MSG
      produced 23 pyrazines, OTDPFA, and gamma-butyrolactone as the major volatile
      compounds. The contents of OTDPFA were lower in MSG plus sugar and MSG-added
      samples, and it is postulated that antioxidant activities were produced in
      cooking.

PMID- 10888565
TI  - Identification of peptides in aggregates formed during hydrolysis of beta
      lactoglobulin B with a Glu and Asp specific microbial protease.
AB  - The purpose of the present study was to identify the peptides responsible for
      aggregate formation during hydrolysis of beta-lactoglobulin by BLP at neutral pH.
      Hydrolysates taken at various stages of aggregate formation were separated into a
      precipitate and a soluble phase and each was analyzed by CE and mass
      spectrometry. The aggregates consisted of six to seven major peptides of which
      four were tentatively identified. The peptides were positively charged at neutral
      pH and had a high charge-to-mass ratio at low pH. The fragment f135-158 seemed to
      be the initiator of aggregation, since it was present at high concentration in
      the aggregates at all stages, and the concentration of this peptide remained low
      in the supernatant. F135-158 contains several basic and acid amino acids
      alternating with hydrophobic amino acids, which is in accordance with formation
      of noncovalently linked aggregates, as previously shown.

PMID- 10888566
TI  - Multiple compound quality index for cold-smoked salmon (Salmo salar) developed by
      multivariate regression of biogenic amines and pH.
AB  - Production of biogenic amines during chill storage of 12 lots of cold-smoked
      salmon was studied. These data allowed for a multiple compound quality index to
      be developed by multivariate regression (partial least square regression). The
      quality index was based on concentrations of cadaverine, histamine, putrescine,
      and tyramine and pH and showed good correlation with sensory assessments.
      Biogenic amines were indicators of spoilage rather than casual agents of spoilage
      off-flavors. Four different biogenic amine profiles were found at the time of
      spoilage in cold-smoked salmon. These were the results of differences in the
      spoilage microflora. Histamine was detected above regulatory limits but below
      toxic levels. Measurements of salt and dry matter for calculation of water phase
      salt could be substituted by rapid water activity measurements.

PMID- 10888567
TI  - Formation of volatile compounds during heating of spice paprika (Capsicum annuum)
      powder.
AB  - Spice paprika (red pepper; Capsicum annuum) is the most cultivated spice
      worldwide and is used mainly for its color and pungency. However, current
      research is also focusing on the flavor as an important parameter. This paper
      deals with the kinetics of the formation of those volatiles that indicate a
      decrease in spice paprika quality due to Maillard reaction, hydrolytic reactions,
      and oxidative degradation reactions of lipids such as fatty acids and
      carotenoids. Spice paprika volatiles were quantitatively analyzed by means of
      headspace gas chromatography (HS-GC) and solid-phase microextraction (SPME)
      followed by gas chromatography-mass spectrometry (GC-MS). The kinetics of their
      formation were investigated, and the respective activation energies determined.
      Strecker aldehyde, acetone, and methanol formation followed a pseudo-zero-order
      reaction kinetic, and formation of dimethyl sulfide (DMS) was characterized by a
      first-order kinetic. The activation energies determined were between 86.3 and
      101.8 for the Strecker aldehydes acetaldehyde (AA), 2-methylpropanal (2-MP), 3
      methylbutanal (3-MB), and 2-methylbutanal (2-MB), 130.7 for acetone, 114.2 for
      methanol, and 109.7 kJ/mol for DMS. The amounts of Strecker aldehydes formed were
      correlated to the concentrations of the corresponding free amino acids present in
      the samples. The formation of hexanal and 6-methyl-5-hepten-2-one in Capsicum
      annuum during processing was confirmed, and the formation of beta-ionone was
      probably described for the first time. During heating, the concentration of
      hexanal increased rapidly. The formation of 6-methyl-5-hepten-2-one confirms that
      Capsicum annuum fruits contain lycopene.

PMID- 10888568
TI  - Glass transition and water effects on sucrose inversion by invertase in a lactose
      sucrose system.
AB  - Enzymatic changes are often detrimental to quality of low-moisture foods. In the
      present study, effects of glass transition and water on sucrose inversion in a
      lactose-sucrose food model were investigated. Amorphous samples were produced by
      freeze-drying lactose-sucrose (2:1)-invertase (20 mg invertase/49.4 g of
      carbohydrate) dissolved in distilled water. Sorption isotherms were determined
      gravimetrically at 24 degrees C. Sucrose hydrolysis was determined by monitoring
      glucose content using a test kit and the amounts of fructose, glucose, and
      sucrose using HPLC. The glass transition temperatures, T(g), at various water
      contents were measured using differential scanning calorimetry (DSC). The BET and
      the GAB sorption models were fitted to experimental data up to a(w) 0.444 and
      0.538, respectively. Water sorption and DSC results suggested time-dependent
      crystallization of sugars at a(w) 0.444 and above. Significant sucrose hydrolysis
      occurred only above T(g), concomitantly with crystallization. Sucrose hydrolysis
      and crystallization were not likely in glassy materials.

PMID- 10888569
TI  - High-pressure effects on lysosome integrity and lysosomal enzyme activity in
      bovine muscle.
AB  - This study was conducted to determine whether the application of high hydrostatic
      pressure could modify the enzymatic activity and membrane integrity of lysosomes
      in muscle. Several combinations of pressure (0-600 MPa) and time (0-300 s) were
      applied to two types of samples: purified enzymes (cathepsin D and acid
      phosphatase) in buffer solution and intact muscle (biceps femoris). The enzymes
      studied showed varying degrees of susceptibility depending on the level of
      pressure, holding time, and environment. Acid phosphatase activity was minimally
      affected by pressure in buffer solution, whereas cathepsin D was modulated
      significantly by the pressure and time applied. The activities of the enzymes
      extracted from meat increased with pressure. The cytochemical observations showed
      the presence of primary and secondary lysosomes in muscles. After pressurization,
      the membrane integrity of the lysosomes was modified. A correlation could be
      established between lysosomal enzymatic activities and the lysosome membrane
      breakdown.

PMID- 10888570
TI  - High-performance liquid chromatographic determination of the glycoalkaloids alpha
      solanine and alpha-chaconine in 12 commercial varieties of Mexican potato.
AB  - The glycoalkaloid content in 12 commercial varieties of Mexican potatoes was
      measured by HPLC in both the peel and the flesh of the potato. The principal
      glycoalkaloids alpha-solanine and alpha-chaconine were present in higher
      concentration in the peel than in the flesh of all varieties. The main alkaloid
      in the peel of the potatoes was alpha-chaconine and comprised about 65-71% of the
      total glycoalkaloids. The high concentration of alpha-chaconine in peel, which is
      more toxic than alpha-solanine, gives more protection to the tuber against
      predators. The total alkaloids in the peel of Alpha, Juanita, Michoacan, Nortena,
      Rosita, and Tollocan varieties were higher than the limit recommended for food
      safety. However, the peel represents less than 10% of the total tuber in most of
      the varieties. The total alkaloids contained in the peel of Atzimba, Lopez,
      Marciana, Montsama, Murca, and Puebla was lower than the limits recommended for
      food safety. The glycoalkaloid content in the boiled peeled potatoes was less
      than 9 mg/100 g but in Alpha, Montsama, and Puebla varieties, both glycoalkaloids
      were absent. According to the results, the consumption of the 12 commercial
      varieties of Mexican potatoes does not represent any danger to human health.

PMID- 10888571
TI  - Influence of storage upon light-induced chlorogenic acid accumulation in potato
      tubers (Solanum tuberosum L.).
AB  - The influence of 2 weeks and 3 months of dark storage upon light-induced
      chlorogenic acid accumulation within tuber tissue of four potato cultivars and
      upon 5-, 4-, and 3-caffeoylquinic acid concentrations within cv. King Edward was
      determined. Storage period significantly affected (P < 0.05) the magnitude of the
      light-induced chlorogenic acid response with accumulation rates 3-4 times higher
      in tubers exposed to light after 2 weeks compared with those placed under light
      after 3 months. Comparison of chlorogenic acid concentrations in controls after 2
      and 3 months of dark storage indicated that tuber chlorogenic concentrations
      decline during prolonged cold store at 5 degrees C. Rates of accumulation in
      response to light were cultivar-dependent with cv. Fianna the most light
      sensitive and cv. Maris Piper relatively light-insensitive. In virtually all
      cases exposure to sodium and fluorescent light promoted higher rates of
      accumulation than did exposure to high-pressure mercury light sources.
      Chlorogenic acid values steadily increased over 15 days of illumination with, in
      the majority of cases, no indication of cessation. Light exposure increased 5-, 4
      , and 3-caffeoylquinic acid accumulation rates in cv. King Edward. Irrespective
      of storage period and light source, ratios of 5-:4-:3-caffeoylquinic acid were
      ca. 85:15:0 at day 0 and 52:42:6 by day 15.

PMID- 10888572
TI  - Co-occurrence of ochratoxin A and citrinin in cereals from Bulgarian villages
      with a history of Balkan endemic nephropathy.
AB  - Cereal samples were collected in 1998 from Bulgarian villages without [control
      village (C), n = 20] or with [endemic villages (E); E1, n = 21; E2, n = 30; E3, n
      = 23] a history of Balkan endemic nephropathy (BEN). Sampling included foods
      (wheat, corn) and feeds (barley, oats, wheat bran). Analysis of ochratoxin A and
      citrinin was done by enzyme immunoassays (EIA), with detection limits of 0.5 and
      5 ng/g, respectively. Ochratoxin A-positive results were confirmed by HPLC after
      immunoaffinity chromatography. Highest toxin levels were found in wheat, wheat
      bran, and oats. For ochratoxin A, the percentages of positives were 35% (C), 29%
      (E1), 30% (E2), and 47% (E3), the mean/median values of positives were 1.5/1.3
      ng/g (C), 11/1.6 ng/g (E1), 18/1.6 ng/g (E2), and 3.5/1.5 ng/g (E3). For
      citrinin, 5.0% (C), 14% (E1), 3.3% (E2), and 13% (E3) were positive, and the
      mean/median values were 6.1/6.1 ng/g (C), 180/83 ng/g (E1), 10/10 ng/g (E2), and
      84/20 ng/g (E3). Highest concentrations of ochratoxin (maximum = 140 ng/g) and
      citrinin (maximum = 420 ng/g) were found in samples from endemic villages. Co
      contamination with ochratoxin A and citrinin was found for one sample (14% of
      positives) from village C and for six samples (22% of positives) from villages E1
      E3. Citrinin levels in these samples were 2-200 times higher than those of
      ochratoxin A.

PMID- 10888573
TI  - Evaluation of gamma-irradiation in cocoa husk.
AB  - gamma-Irradiation was investigated as a technique to improve the hygienic quality
      of cocoa husk. Cocoa husk is a byproduct of cocoa bean processing industry. It
      contains approximately 57.5% (w/w) dietary fiber (nonstarch polysaccharides plus
      lignin), 15% (w/w) crude protein, 10.7% (w/w) mineral elements, 2.32% (w/w) cocoa
      butter, and 2.8% (w/w) carbohydrates (free sugars plus starch). The effect of
      irradiation on the growth rates of microorganisms are reported. Total counts,
      enterobacteriaceae, coliforms, Staphylococcus aureus, Streptococcus "D" of
      Lancefield, and yeast and mold counts before and after irradiation at 5, 8, and
      10 kGy were determined. Cocoa husk was irradiated in open containers. An
      irradiation dose of 5 kGy was already sufficient to decrease the microbial counts
      to a very low level. No alteration in dietary fiber was measured in the
      irradiated product and no significant differences were detected between
      irradiated and nonirradiated cocoa husk.

PMID- 10888574
TI  - Formation of N-(Nitrosomethyl)urea in stomachs of experimental pigs and human
      volunteers given fish sauce in vivo.
AB  - N-(Nitrosomethyl)urea (NMU) was characterized in carcinogenic nitrosated fish
      sauce recently (Deng et al. J. Agric. Food Chem. 1998, 46, 202-205; Biomed.
      Environ. Sci. 1999, 12, 54-61). To study the possibility of intragastric
      synthesis of NMU, experimental mini-pigs surgically fitted with a flexible
      stomach cannula and human volunteers were used. Fish sauce samples (20-30 mL) and
      nitrite were injected into the gastric lumen through the cannula for pigs or
      taken orally for human volunteers. Gastric juice samples were taken out 30 min
      later. Concentration of NMU in condensed extracts of these samples was analyzed
      with HPLC-photohydrolysis-pyrolysis-thermal energy analyzer. Results showed that
      there was formation of NMU in the gastric lumen of both models in vivo and that
      the formation of NMU was nitrite- and pH-dependent. NMU was also detectable in
      the condensed extract of 100 mL of a mixture of pooled fasting human gastric
      juice samples and fish sauce sample (9:1, v/v) after treatment with 500
      micromol/L of nitrite in vitro. In conclusion, there is intragastric formation of
      NMU, even at natural amounts of nitrite.

PMID- 10888575
TI  - Migration of organophosphorus insecticides cyanophos and prothiofos residues from
      impregnated paper bags to Japanese apple-pears (Pyrus pyrifolia nakai cv.
      Nijisseiki).
AB  - Bags impregnated with the organophosphorus pesticides prothiofos and cyanophos in
      three levels were used to cover Japanese apple-pears to protect them from
      insects. The amounts of prothiofos residue in the bags collected 4 months after
      application ranged from 0 to 34% of the amounts (81, 148, and 333 microg) found
      in the bags prior to a bagging. The amounts of cyanophos residue in bags
      collected 4 months after application ranged from 11 to 29% of the amounts (335,
      2860, and 3740 microg) present prior to a bagging. Amounts of prothiofos found in
      fruits after 4 months ranged from 0 to 0.076 ppm. Amounts of cyanophos found in
      fruits after 4 months ranged from 0 to 0.011 ppm. Results of the present study
      indicate that these two pesticides migrated from pesticide-impregnated bags to
      fruits during the growing season.

PMID- 10888576
TI  - Degradation of malathion and phenthoate by glutathione reductase in wheat germ.
AB  - Residual malathion in wheat was estimated at a lower value when analysis was
      performed by extraction with acetone after addition of water to swell the wheat,
      according to the Japanese Bulletin Method. The supernatant of the wheat
      homogenate showed degradation not only of malathion but also of phenthoate.
      Malathion and phenthoate were not degraded by the boiled supernatant of the wheat
      homogenate. It was presumed for this reason that glutathione reductase (GR; EC
      1.6. 4.2) in the wheat degraded malathion. The following results were obtained:
      (1) GR originating in wheat could degrade malathion and phenthoate. (2) The
      degradation of malathion by the GR was inhibited by excessive GSSG. (3) There was
      a high correlation between GR activity and malathion degradation activity of the
      supernatant of wheat homogenates. It is likely that GR acted on the specific
      structure of malathion and phenthoate, the S=P-S bond, and the blanch structure
      bonding with the sulfur atom. Following the above, extraction with acetone after
      addition of water (the Japanese Bulletin Method) should be replaced by extraction
      with pure organic solvent and without addition of water for swelling.

PMID- 10888577
TI  - Interaction of cyclohexanediones with acetyl coenzyme-A carboxylase and an
      artificial target-site antibody mimic: a comparative molecular field analysis.
AB  - Similarities and differences between steric and electrostatic potentials of a
      monoclonal-antibody-based surrogate of a herbicide target-site and its in vitro
      enzyme target were investigated using three-dimensional quantitative structure
      activity relationship comparative molecular field analysis (3D-QSAR CoMFA). Two
      separate, five-component, partial least squares CoMFA models were developed to
      compare the interaction of cyclohexanedione herbicides with their target site,
      acetyl coenzyme-A carboxylase (ACCase; EC 6.4.1.2) and a cyclohexanedione
      pharmacophore-specific monoclonal antibody (mAb A). On the basis of CoMFA models,
      similarities in steric and electrostatic requirements around position 2 of the
      binding site for the oxime functional group of the cyclohexanedione molecule
      appear to be crucial for interaction of the herbicide with both ACCase and mAb A.
      These similarities explain the observed quantitative relationship between binding
      of cyclohexandedione herbicides to ACCase mAb A. Furthermore, these results
      support the production and use of mAb-based surrogates of pesticide targets as
      screening tools in pesticide discovery programs.

PMID- 10888578
TI  - Search for a standard phytotoxic bioassay for allelochemicals. Selection of
      standard target species.
AB  - In the search for a standard bioassay of phytotoxicity for allelochemicals, 22
      commercial varieties of eight plant species [four dicotyledons: lettuce
      (Compositae), carrot (Umbelliferae), cress (Cruciferae), tomato (Solanaceae); and
      four monocotyledons: onion (Liliaceae), barley, wheat, and corn (Gramineae)]
      proposed as models for the most common weed families have been tested at
      different pH and solution volumes per set conditions. Nine commercial varieties
      selected as standard target species (STS) were tested with standard commercial
      herbicides to ensure their sensitivity to phytotoxic compounds. Results are
      discussed to establish the proper growth requirements, and sensitivity of
      commercial seeds of STS and to find the most suitable commercial herbicides that
      allow comparison with an internal standard to validate the response of potential
      allelochemicals.

PMID- 10888579
TI  - Field trials to determine residues of chlozolinate in table grapes.
AB  - Chlozolinate (Serinal) is a dicarboximide fungicide used in southern European
      countries principally on grapes. Maximum residue levels have not yet been set by
      FAO/WHO and are under evaluation in the EU. Field trials have been carried out in
      Greece on two varieties of table grapes (Cardinal and Victoria) during two
      consecutive years to assess residues remaining after application according to
      good agricultural practice. Analysis using a multiresidue method with gas
      chromatography (ECD) showed that the parent compound decays with a first-order
      rate constant of 0.057 +/- 0.011 day(-)(1) and that residues had fallen below the
      proposed MRL of 5 mg/kg in all samples by 21 days postapplication (the proposed
      PHI). The contribution of the main metabolite, S1, to the total residue is
      generally <20%. Washing removes a substantial amount (up to 80%) of chlozolinate,
      which appears to be nonsystemic on grapes, thus reducing real consumer exposure
      to this pesticide.

PMID- 10888580
TI  - Insecticidal and fumigant activities of Cinnamomum cassia bark-derived materials
      against Mechoris ursulus (Coleoptera: attelabidae).
AB  - The insecticidal and fumigant activities of Cinnamomum cassia (Blume) bark
      derived materials against the oak nut weevil (Mechoris ursulus Roelofs) were
      examined using filter paper diffusion and fumigation methods and compared to
      those of the commercially available Cinnamomum bark-derived compounds (eugenol,
      salicylaldehyde, trans-cinnamic acid, and cinnamyl alcohol). The biologically
      active constituent of the Cinnamomum bark was characterized as trans
      cinnamaldehyde by spectroscopic analysis. In a test with the filter paper
      diffusion method, trans-cinnamaldehyde showed 100 and 83.3% mortality at rates of
      2.5 and 1.0 mg/filter paper, respectively. At 2.5 mg/paper, strong insecticidal
      activity was produced from eugenol (90.0% mortality) and salicylaldehyde (88.
      9%), whereas trans-cinnamic acid revealed moderate activity (73.3%). At 5
      mg/paper, weak insecticidal activity (50.0%) was produced from cinnamyl alcohol.
      In a fumigation test, the Cinnamomum bark-derived compounds were much more
      effective against M. ursulus larvae in closed cups than in open ones. These
      results indicate that the insecticidal activity of test compounds was
      attributable to fumigant action, although there is also significant contact
      toxicity. As a naturally occurring insect-control agent, the Cinnamomum bark
      derived materials described could be useful as a new preventive agent against
      damage caused by M. ursulus.

PMID- 10888581
TI  - Nature of the residue of [(14)C]Cloransulam-methyl in lactating goats.
AB  - Two lactating goats were given a daily oral dose of either [UL-aniline-(14)C; AN]
      or [triazolopyrimidine-7,9-(14)C; TP]cloransulam-methyl for 5 consecutive days.
      Each animal received a dietary equivalent of approximately 10 mg/kg of test
      material, approximately 2225 times the realistic maximum dietary exposure for a
      dairy animal. Milk, urine, and feces samples were collected in the morning and
      afternoon for each animal. Each goat was sacrificed within 23 h of receiving the
      last dose, and the liver, kidneys, samples of blood, fat, muscle, and
      gastrointestinal tract contents, and urine from the bladder were collected. All
      of these samples were analyzed for (14)C content. Cloransulam-methyl (CM) was
      rapidly excreted by the animals, with 99.9% of the recovered radioactivity
      appearing in the urine and feces. Radiochemical analysis showed very low
      residues, with the highest being in the kidneys at 0.122 and 0. 128 mg equiv of
      CM/kg (AN and TP labeled compounds, respectively). Radioactive residues were
      extracted and fractionated from kidney, liver, and milk. Analysis showed
      approximately 0.066 mg/kg CM in the kidney but <0.003 mg/kg in the liver. Only
      one metabolite, cloransulam, was identified (in liver, 9.5% of total radioactive
      residue; 0.005 mg/kg). All other metabolites were present at lower levels.
      Sulfonanilide bridge cleavage was not a significant degradation route for
      cloransulam-methyl in ruminants. These data indicated a very low bioaccumulation
      potential for cloransulam-methyl and its metabolites in ruminants. For a ruminant
      exposed to anticipated levels of cloransulam-methyl in its diet, parent and
      metabolites, in total, would not be expected to exceed 50 ng/kg in the kidney and
      liver.

PMID- 10888582
TI  - Synthesis, fungicidal activity, and QSAR of a series of 2-dichlorophenyl-3
      triazolylpropyl ethers.
AB  - A series of new alkyl and arylalkyl ethers of 2-(2, 4-dichlorophenyl)-3-(1H-1,2,4
      triazol-1-yl)propanol, related to the fungicide tetraconazole, were synthesized
      and tested in vitro or in vivo against seven common pathogens in comparison with
      tetraconazole. In vitro, most of them exhibited a broad spectrum of activity and
      an efficacy of the same order of magnitude of the standard, but the activity was
      influenced by the nature of the substituents. A QSAR study showed that
      lipophilicity is a major positive parameter in affecting the activity; the second
      relevant parameter is mu, whereas geometrical descriptors indicate that linear
      and narrow substituents are more suitable than wide ones. In in vivo assays some
      compounds had good activity on bean rust, either protective or curative. Sterol
      analysis showed that the mechanism of action is due to inhibition of 14alpha
      demethylase.

PMID- 10888583
TI  - Simple method for large scale isolation of the cyclic arylhydroxamic acid DIMBOA
      from maize (Zea mays L.).
AB  - The 2-beta-O-D-glucoside of the cyclic arylhydroxamic acid 2, 4-dihydroxy-7
      methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) that occurs in large amounts in
      young maize shoots (Zea mays L.) is converted enzymatically to its aglycone upon
      tissue damage. The aglycone DIMBOA possesses strong biologically activity toward
      various organisms whereas the glucoside is almost biologically inactive. A simple
      procedure yielding DIMBOA in gram quantities, from 7-day-old maize seedlings, was
      developed by using solid-phase extraction.

PMID- 10888584
TI  - Synthesis and cytokinin activity of fluorescent 7-Phenylethynylimidazo[4,5
      b]pyridine and its riboside.
AB  - 7-Phenylethynylimidazo[4,5-b]pyridine and its riboside have been newly developed
      as fluorescent carbon-substituted cytokinin analogues. Palladium-catalyzed
      coupling of 7-iodo-3-(tri-O-acetyl-beta-D-ribofuranosyl)imidazo[4,5-b]pyridine
      with phenylacetylene followed by ammonolysis afforded the 7-phenylethynyl
      riboside via its tri-O-acetate. Acid hydrolysis of the riboside provided its free
      base, which showed a marked enhancement in fluorescence intensity in an aqueous
      alkaline solution. The free base and its riboside were more active than the
      corresponding 6-phenylethynylpurine and its riboside, respectively, in Amaranthus
      betacyanin and tobacco callus bioassays. Surprisingly, the imidazo[4,5-b]pyridine
      base exhibited strong cytokinin activity comparable to that of N(6)-benzyladenine
      in the tobacco callus bioassay. This compound would be useful for studying
      localization and transport of cytokinins in cells or tissues of plants.

PMID- 10888585
TI  - Degradation of primisulfuron by a combination of chemical and microbiological
      processes.
AB  - Microbial degradation of the herbicide primisulfuron was investigated using
      enrichment cultures from contaminated soils and 20 axenic cultures. At neutral
      pH, no disappearance of the herbicide was detected either in the enrichment
      cultures or in the growth media of the axenic microbial cultures. During the
      growth of some of the microbial strains, however, the pH of the medium dropped
      below 6, resulting in the hydrolysis of primisulfuron. The rate of primisulfuron
      hydrolysis was clearly pH dependent; primisulfuron was more persistent in neutral
      or weakly basic solutions than in acidic solutions. After hydrolysis of the
      herbicide, four products were observed. These were identified as methyl 2
      (aminosulfonyl)benzoate, 2-amino-4,6-(difluoromethoxy)pyrimidine, 2-N-[[[[[4, 6
      bis(difluoromethoxy)-2-pyrimidinyl]amino]carbonyl]amino]sulfonyl ]be nzoic acid,
      and 2-(aminosulfonyl)benzoic acid. After hydrolysis, it was found that the fungus
      Phanerochaete chrysosporium mineralized 27 and 24% of (14)C-phenyl- and (14)C
      pyrimidine-labeled products, respectively, after 24 days of incubation.
      Similarly, Trametes versicolor mineralized 13 and 11% of (14)C-phenyl- and (14)C
      pyrimidine-labeled hydrolysis products, respectively. In addition, primisulfuron
      in a hydrolytically stable solution, at pH 7. 0, was rapidly decomposed after
      ultraviolet irradiation, and two photolysis products were isolated
      [methylbenzoate and 4, 6-(difluoromethoxy)pyrimidin-2-ylurea]. When (14)C-phenyl
      labeled primisulfuron was exposed to photolysis for 24 h, 32% of the initial
      radioactivity was recovered as (14)CO(2), whereas no (14)CO(2) was detected if
      the herbicide was labeled at the (14)C-pyrimidine position. Mineralization of
      (14)C-pyrimidine-labeled products of photolyzed primisulfuron by P. chrysosporium
      was approximately 25% after 24 days. These results clearly indicate that
      hydrolysis and photolysis of primisulfuron facilitated microbial degradation.

PMID- 10888586
TI  - Study on the hydrolysis of 2-chlorobenzamide.
AB  - It is reported that 2-chlorobenzamide, one of the chief degradation products of
      CCU (1-(2-chlorobenzoyl)-3-(4-chlorophenyl) urea), a new insect growth regulator,
      is a potential carcinogen, but few studies about its environmental stability have
      been found. This paper is concerned with the hydrolysis of 2-chlorobenzamide as
      part of the environmental study of CCU. The results showed that 2-chlorobenzamide
      is relatively stable in solutions of pH = 6 and 8, for which the rate constants
      are 0.00286 h(-)(1) (R = 99.13%, SD = 0. 0095) and 0.00109 h(-)(1) (R = 96.70%,
      SD = 0.0072), respectively. Hydrolysis was more rapid in acidic (pH = 5),
      alkaline (pH = 10), and neutral (pH = 7) environments, with hydrolytic rate
      constants of 0.00417h(-)(1) (R = 95.76%, SD = 0.0390), 0.00411h(-)(1) (R =
      99.89%, SD = 0.0162) and 0.00408h(-)(1) (R = 98.29%, SD = 0.0237), respectively.
      The change of the rate of hydrolysis with pH showed two minima at 25 degrees C.
      Temperature has some impact on the hydrolysis, showing at higher temperature the
      larger rate of reaction.

PMID- 10888587
TI  - GC-MS analysis of essential oils from some Greek aromatic plants and their
      fungitoxicity on Penicillium digitatum.
AB  - The isolated essential oils from seven air-dried plant species were analyzed by
      gas chromatography-mass spectrometry (GC-MS). Thymus vulgaris (thyme), Origanum
      vulgare (oregano), and Origanumdictamus (dictamus) essential oils were found to
      be rich in phenolic compounds representing 65.8, 71.1, and 78.0% of the total
      oil, respectively. Origanum majorana (marjoram) oil was constituted of
      hydrocarbons (42.1%), alcohols (24.3%), and phenols (14.2%). The essential oil
      from Lavandula angustifolia Mill. (lavender) was characterized by the presence of
      alcohols (58.8%) and esters (32.7%). Ethers predominated in Rosmarinus
      officinalis (rosemary) and Salvia fruticosa (sage) essential oils, constituting
      88.9 and 78.0%, respectively. The radial growth, conidial germination, and
      production of Penicillium digitatum were inhibited completely by oregano, thyme,
      dictamus, and marjoram essential oils at relatively low concentrations (250-400
      microg/mL). Lavender, rosemary, and sage essential oils presented less inhibitory
      effect on the radial growth and conidial germination of P. digitatum. Conidial
      production of P. digitatum was not affected by the above oils at concentrations
      up to 1000 microg/mL. Apart from oregano oil, all essential oils were more
      effective in the inhibition of conidial germination than of radial growth. The
      monoterpene components, which participate in essential oils in different
      compositions, seem to have more than an additive effect in fungal inhibition.

PMID- 10888588
TI  - Hydrolysis kinetics of fenthion and its metabolites in buffered aqueous media.
AB  - This study investigates the hydrolysis kinetics of fenthion and its five
      oxidation metabolites in pH 7 and pH 9 buffered aqueous media at 25, 50, and 65
      degrees C. Five metabolites and three hydrolysis products were synthesized and
      purified. The reactant and the corresponding hydrolysis products were determined
      by HPLC. Rate constant and half-life studies revealed that fenthion and its
      metabolites were relatively stable in neutral media, and their stability
      decreased as pH increased. The half-lives at 25 degrees C ranged from 59.0 days
      for fenthion to 16.5 days for fenoxon sulfone at pH 7, and from 55.5 days for
      fenthion to 9.50 days for fenoxon sulfone at pH 9; half-lives were greatly
      reduced at elevated temperatures. The activation energy (E(a)) was found to range
      from 16.7 to 22.1 kcal/mol for the compounds investigated. The phenol hydrolysis
      product of fenthion and fenoxon, 3-methyl-4-methylthiophenol was not stable in pH
      7 and pH 9 buffered solutions at 50 degrees C, whereas 3-methyl-4
      methylsulfonylphenol and 3-methyl-4-methylsulfinylphenol were relatively stable
      under the same conditions. At pH 9, the primary hydrolysis mechanisms of fenthion
      and its oxidation metabolites were combination of hydroxide ion and neutral water
      molecule attacking on the P atom to form corresponding phenol derivatives. Under
      neutral conditions, the primary hydrolysis mechanisms of fenthion and its
      oxidation metabolites were assumed to be the combination of water molecule
      attacking on the P atom to form phenol derivatives and on the C atom to yield
      dealkylation products.

PMID- 10888589
TI  - Kombucha fermentation and its antimicrobial activity.
AB  - Kombucha was prepared in a tea broth (0.5% w/v) supplemented with sucrose (10%
      w/v) by using a commercially available starter culture. The pH decreased steadily
      from 5 to 2.5 during the fermentation while the weight of the "tea fungus" and
      the OD of the tea broth increased through 4 days of the fermentation and remained
      fairly constant thereafter. The counts of acetic acid-producing bacteria and
      yeasts in the broth increased up to 4 days of fermentation and decreased
      afterward. The antimicrobial activity of Kombucha was investigated against a
      number of pathogenic microorganisms. Staphylococcus aureus, Shigella sonnei,
      Escherichia coli, Aeromonas hydrophila, Yersinia enterolitica, Pseudomonas
      aeruginosa, Enterobacter cloacae, Staphylococcus epidermis, Campylobacter jejuni,
      Salmonella enteritidis, Salmonella typhimurium, Bacillus cereus,
      Helicobacterpylori, and Listeria monocytogenes were found to be sensitive to
      Kombucha. According to the literature on Kombucha, acetic acid is considered to
      be responsible for the inhibitory effect toward a number of microbes tested, and
      this is also valid in the present study. However, in this study, Kombucha proved
      to exert antimicrobial activities against E. coli, Sh. sonnei, Sal. typhimurium,
      Sal. enteritidis, and Cm. jejuni, even at neutral pH and after thermal
      denaturation. This finding suggests the presence of antimicrobial compounds other
      than acetic acid and large proteins in Kombucha.

PMID- 10888590
TI  - Effect of cationic membrane permselectivity on the efficiency of skim milk
      electroacidification.
AB  - Bipolar membrane electroacidification (BMEA) uses the property of bipolar
      membranes to split water and the demineralization action of cation-exchange
      membranes (CEM). As milk mineral salt content is very sensitive to ionic strength
      and pH changes, the aim of this study was to better understand the effect of
      changes in mineral content during pH decrease and demineralization of skim milk.
      The objectives were to investigate the effect of different cationic permselective
      membranes (CSV and CMX membranes) on skim milk cation migration and protein
      precipitation during BMEA. The permselectivity of both membranes tested does not
      influence the final efficiency of BMEA. The purity of the bovine milk casein
      isolates produced was similar to or higher (97-98% versus 93.4-96.7) than those
      of commercial isolates, due to a reduced ash content (1.2 versus 2.0-3. 8%)
      resulting from the CEM demineralizing phenomenon. For both membranes, the main
      ionic species to migrate was the potassium ions.

PMID- 10888591
TI  - Overexpression of the soluble form of chicken cystatin in Escherichia coli and
      its purification.
AB  - A cDNA encoding chicken cystatin was cloned into the pET-23a(+) expression vector
      and then transformed into Escherichia coli AD494(DE3)pLysS expression host. An
      active soluble form of cystatin was expressed in the cytoplasm of E. coli induced
      by isopropyl beta-D-thiogalactopyranoside. The recombinant chicken cystatin was
      purified to electrophoretic homogeneity by a simple and rapid method involving
      heat treatment and Sephacryl S-100 gel filtration chromatography. The recombinant
      cystatin behaved as a thermal-stable protein and exhibited papain-like protease
      inhibition activity comparable to the natural chicken cystatin.

PMID- 10888592
TI  - Molecular tools for the identification of Tuber melanosporum in agroindustry.
AB  - Tuber melanosporum Vitt., Tuber magnatum Pico, and Tuber uncinatum Chat. can be
      differentiated by their morphological characters. Fraud problems have arisen
      recently with the importation to Europe of truffles from China. T. melanosporum
      is morphologically very close, but distinct from the Chinese species [Tuber
      indicum (Cooke and Massee) and T. himalayense BC (Zhang and Winter)]. We have
      optimized molecular tools to unequivocally identify T. melanosporum. DNA
      extraction from ascocarps of black truffles is not straightforward. Problems to
      obtain pure DNA are due to high contents of phenolic compounds, melanine, and
      various polymers (proteins, polysaccharides, etc). These compounds coprecipitate
      with the DNA during extraction and strongly inhibit the PCR reaction. We have
      developed an efficient and reliable protocol for DNA extraction from truffle
      ascocarps. It was used successfully for DNA extraction from mycorrhizal root tips
      as well as from canned preparations of T. melanosporum. Several approaches to
      identify T. melanosporum by PCR were developed. Two specific primers for T.
      melanosporum were designed after comparison of the ITS region of this species
      with those of three Chinese fungi. They proved to be efficient to specifically
      detect the presence of T. melanosporum by PCR. The mycorrhizal status of trees
      inoculated with T. melanosporum but unable to produce truffles was confirmed in a
      single-step PCR reaction. A multiplex PCR approach was also developed with three
      sets of primers (including a specific one for Chinese truffles) to detect, in one
      PCR reaction, the presence of any other Tuber species mixed with T. melanosporum
      ascocarps. This optimized protocol, in association with the specific primers we
      designed, is applicable to quality control in the truffle industry from the
      production stages to final commercial products.

PMID- 10888593
TI  - Derivation and properties of recombinant Fab antibodies to coplanar
      polychlorinated biphenyls.
AB  - Recombinant Fab antibodies (rFabs) specific for coplanar polychlorinated
      biphenyls (PCBs) were derived from a hybridoma cell line (Chiu et al. Anal. Chem.
      1995, 67, 3829-3839). Immunoglobulin V(H)-C(H1) and V(L)-C(L) sequences from S2B1
      messenger RNA were amplified by PCR and cloned into the M13 phagemid vector
      pComb3H. Phage displaying rFab were enriched by panning on a PCB hapten conjugate
      and expressed as soluble rFabs in Escherichia coli XL-1 Blue. Two rFab clones
      competitively bound PCBs 77 and 126 with half-maximal inhibition (I(50)) of 10-13
      ppb in indirect and direct enzyme immunoassays (EIAs), with selectivity nearly
      identical to that of whole S2B1 IgG and its Fab fragments prepared by papain
      digestion. These results, and comparison of N-terminal amino acid sequences of
      MAb S2B1 and the rFab, indicated that rFab S2B1 is a functional copy of the MAb.
      The rFab S2B1 sequences have 75-89% sequence identity with antibodies that bind
      nitrophenyl haptens and are being used to construct a three-dimensional
      computational model of the PCB binding site.

PMID- 10888595
TI  - Effects of the sniffing port air makeup in gas chromatography-olfactometry

PMID- 10888594
TI  - Effective deacetylation of chitin under conditions of 15 psi/121 degrees C.
AB  - Deacetylation of chitin under autoclaving conditions (15 psi/121 degrees C) was
      evaluated for the preparation of chitosan under different NaOH concentrations and
      reaction times. Deacetylation was effectively achieved by treatment of chitin
      under elevated temperature and pressure with 45% NaOH for 30 min and a
      solids/solvent ratio of 1:15. Treated chitosan showed similar nitrogen content
      (7.42%), degree of deacetylation (90.4%), and molecular mass (1560 kDa) but
      significantly higher viscosity values (2025 cP) compared with those (7.40%,
      87.6%, 1304 kDa, and 143 cP, respectively) of a commercial chitosan. Reduction of
      the solids/solvent ratio from 1:15 to 1:10 did not affect degree of
      deacetylation, viscosity, and molecular mass of chitosan.

PMID- 10888596
TI  - Genome search for susceptibility loci of common idiopathic generalised
      epilepsies.
AB  - Genetic factors play a major role in the aetiology of idiopathic generalised
      epilepsies (IGEs). The present genome scan was designed to identify
      susceptibility loci that predispose to a spectrum of common IGE syndromes. Our
      collaborative study included 130 IGE-multiplex families ascertained through a
      proband with either an idiopathic absence epilepsy or juvenile myoclonic
      epilepsy, and one or more siblings affected by an IGE trait. In total, 413
      microsatellite polymorphisms were genotyped in 617 family members. Non-parametric
      multipoint linkage analysis, using the GeneHunter program, provided significant
      evidence for a novel IGE susceptibility locus on chromosome 3q26 (Z(NPL) = 4.19
      at D3S3725; P = 0.000017) and suggestive evidence for two IGE loci on chromosome
      14q23 (Z(NPL) = 3.28 at D14S63; P = 0.000566), and chromosome 2q36 (Z(NPL) = 2.98
      at D2S1371; P = 0.000535). The present linkage findings provide suggestive
      evidence that at least three genetic factors confer susceptibility to generalised
      seizures in a broad spectrum of IGE syndromes. The chromosomal segments
      identified harbour several genes involved in the regulation of neuronal ion
      influx which are plausible candidates for mutation screening.

PMID- 10888597
TI  - Increased levels of apoptosis in the prefusion neural folds underlie the
      craniofacial disorder, Treacher Collins syndrome.
AB  - Treacher Collins syndrome (TCS) is an autosomal dominant disorder of human
      craniofacial development that results from loss-of-function mutations in the gene
      TCOF1. Although this gene has been demonstrated to encode the nucleolar
      phosphoprotein treacle, the developmental mechanism underlying TCS remains
      elusive, particularly as expression studies have shown that the murine
      orthologue, Tcof1, is widely expressed. To investigate the molecular pathogenesis
      of TCS, we replaced exon 1 of Tcof1 with a neomycin-resistance cassette via
      homologous recombination in embryonic stem cells. Tcof1 heterozygous mice die
      perinatally as a result of severe craniofacial anomalies that include agenesis of
      the nasal passages, abnormal development of the maxilla, exencephaly and
      anophthalmia. These defects arise due to a massive increase in the levels of
      apoptosis in the prefusion neural folds, which are the site of the highest levels
      of Tcof1 expression. Our results demonstrate that TCS arises from
      haploinsufficiency of a protein that plays a crucial role in craniofacial
      development and indicate that correct dosage of treacle is essential for survival
      of cephalic neural crest cells.

PMID- 10888598
TI  - Restricted polymorphism of the mannose-binding lectin gene of indigenous
      Australians.
AB  - Mannose-binding lectin (MBL) is an important complement-activating protein of the
      human innate immune system. Deficiency of MBL is associated with an increased
      risk of various infections and arises from three structural gene mutations in
      exon 1 (variants B, C and D) and/or the presence of a low efficiency promoter.
      The C allele is found in sub-Saharan Africa whereas the B allele is found
      elsewhere, suggesting that these mutations occurred after the suggested hominid
      migration out of Africa [100-150 000 years before present (BP)]. Paradoxically,
      these alleles may have a selective advantage in protection against intracellular
      pathogens and occur at particularly high frequencies in sub-Saharan Africa (C
      variant) and South America (B variant). Since hominids reached Australia at least
      50 000 years ago, a study of MBL polymorphisms in the indigenous population was
      of interest. Using heteroduplex technology we found a paucity of MBL structural
      gene mutations in two population groups from geographically distinct regions. Of
      293 individuals tested, 289 were wild-type and four were heterozygous for either
      the B or D allele. In each individual with an MBL mutation the HLA haplotype
      profile suggested some Caucasian admixture. We also found a restricted range of
      MBL promoter haplotypes and the serum MBL levels were higher than those of any
      other ethnic group studied to date (median 3.07 microg/ml). Our data suggest that
      the B mutation probably arose between 50 000 and 20 000 BP. Its absence from the
      founder gene pool of indigenous Australians may also partly explain their
      vulnerability to intracellular infections such as tuberculosis.

PMID- 10888599
TI  - The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar
      targeting signal equivalent to the HIV-1 regulatory proteins.
AB  - Fragile X syndrome is caused by the absence of the fragile X mental-retardation
      protein (FMRP). FMRP and the fragile X-related proteins 1 and 2 (FXR1P and FXR2P)
      form a gene family with functional similarities, such as RNA binding,
      polyribosomal association and nucleocytoplasmic shuttling. In a previous study,
      we found that FMRP and FXR1P shuttle between cytoplasm and nucleoplasm, while
      FXR2P shuttles between cytoplasm and nucleolus. The nuclear and nucleolar
      targeting properties of these proteins were investigated further. Here, we show
      that FXR2P contains in its C-terminal part, a stretch of basic amino acids
      'RPQRRNRSRRRRFR' that resemble the nucleolar-targeting signal (NoS) of the viral
      protein Rev. This particular sequence is also present within exon 15 of the FXR1
      gene. This exon undergoes alternative splicing and is therefore only present in
      some of the FXR1P isoforms. We investigated the intracellular distribution of
      various FXR1P isoforms with (iso-e and iso-f) and without (iso-d) the potential
      NoS in transfected COS cells treated with the nuclear export inhibitor leptomycin
      B. Both iso-e and iso-f showed a nucleolar localization, as observed for FXR2P;
      iso-d was detected in the nucleo-plasm outside the nucleoli. Further, when a
      labelled 16-residue synthetic peptide corresponding to the NoS of FXR1P was added
      to human fibroblast cultures a clear nucleolar signal was observed. Based on
      these data we argue that the intranuclear distribution of FXR2P and FXR1P
      isoforms is very likely to be mediated by a similar NoS localized in their C
      terminal region. This domain is absent in some FXR1P isoforms as well as in all
      FMRP isoforms, suggesting functional differences for this family of proteins,
      possibly related to RNA metabolism in different tissues.

PMID- 10888600
TI  - Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early
      event in the pathogenesis of meningiomas.
AB  - Meningiomas are common nervous system tumors, whose molecular pathogenesis is
      poorly understood. To date, the most frequent genetic alteration detected in
      these tumors is loss of heterozygosity (LOH) on chromosome 22q. This finding led
      to the identification of the neurofibromatosis 2 (NF2) tumor suppressor gene on
      22q12, which is inactivated in 40% of sporadic meningiomas. The NF2 gene product,
      merlin (or schwannomin), is a member of the protein 4.1 family of membrane
      associated proteins, which also includes ezrin, radixin and moesin. Recently, we
      identified another protein 4.1 gene, DAL-1 (differentially expressed in
      adenocarcinoma of the lung) located on chromosome 18p11.3, which is lost in
      approximately 60% of non-small cell lung carcinomas, and exhibits growth
      suppressing properties in lung cancer cell lines. Given the homology between DAL
      1 and NF2 and the identification of significant LOH in the region of DAL-1 in
      lung, breast and brain tumors, we investigated the possibility that loss of
      expression of DAL-1 was important for meningioma development. In this report, we
      demonstrate DAL-1 loss in 60% of sporadic meningiomas using LOH, RT-PCR, western
      blot and immunohistochemistry analyses. Analogous to merlin, we show that DAL-1
      loss is an early event in meningioma tumorigenesis, suggesting that these two
      protein 4.1 family members are critical growth regulators in the pathogenesis of
      meningiomas. Furthermore, our work supports the emerging notion that membrane
      associated alterations are important in the early stages of neoplastic
      transformation and the study of such alterations may elucidate the mechanism of
      tumorigenesis shared by other tumor types.

PMID- 10888601
TI  - Human adenylosuccinate lyase (ADSL), cloning and characterization of full-length
      cDNA and its isoform, gene structure and molecular basis for ADSL deficiency in
      six patients.
AB  - Adenylosuccinate lyase (ADSL) is a bifunctional enzyme acting in de novo purine
      synthesis and purine nucleotide recycling. ADSL deficiency is a selectively
      neuronopathic disorder with psychomotor retardation and epilepsy as leading
      traits. Both dephosphorylated enzyme substrates, succinylaminoimidazole
      carboxamide riboside (SAICAr) and succinyladenosine (S-Ado), accumulate in the
      cerebrospinal fluid (CSF) of affected individuals with S-Ado/SAICAr concentration
      ratios proportional to the phenotype severity. We studied the disorder at various
      levels in a group of six patients with ADSL deficiency. We identified the
      complete ADSL cDNA and its alternatively spliced isoform resulting from exon 12
      skipping. Both mRNA isoforms were expressed in all the tissues studied with the
      non-spliced form 10-fold more abundant. Both cDNAs were expressed in Escherichia
      coli and functionally characterized at the protein level. The results showed only
      the unspliced ADSL to be active. The gene consists of 13 exons spanning 23 kb.
      The promotor region shows typical features of the housekeeping gene. Eight
      mutations were identified in a group of six patients. The expression studies of
      the mutant proteins carried out in an attempt to study genotype-phenotype
      correlation showed that the level of residual enzyme activity correlates with the
      severity of the clinical phenotype. All the mutant enzymes studied in vitro
      displayed a proportional decrease in activity against both of their substrates.
      However, this was not concordant with strikingly different concentration ratios
      in the CSF of individual patients. This suggests either different in vivo enzyme
      activities against each of the substrates and/or their different turnover across
      the CSF-blood barrier, which may be decisive in determining disease severity.

PMID- 10888602
TI  - A novel ryanodine receptor mutation and genotype-phenotype correlation in a large
      malignant hyperthermia New Zealand Maori pedigree.
AB  - Malignant hyperthermia (MH) is a pharmacogenetic disorder that predisposes to a
      sometimes fatal hypermetabolic reaction to halogenated anaesthetics. MH is
      considered to originate from abnormal regulation of skeletal muscle Ca(2+)
      release. Current diagnosis of MH susceptibility (MHS) relies on in vitro
      contracture testing (IVCT) of skeletal muscle. The ryanodine receptor (RYR1)
      encoding the major Ca(2+) release channel in the skeletal muscle sarcoplasmic
      reticulum has been shown to be mutated in a number of MH pedigrees. The large
      Maori pedigree reported here is the largest MHS pedigree investigated to date and
      comprises five probands who experienced clinical episodes of MH and 130 members
      diagnosed by the IVCT. Sequencing of the 15 117 bp RYR1 cDNA in a MHS individual
      from this pedigree identified a novel C14477T transition that results in a
      Thr4826 to Ile substitution in the C-terminal region/transmembrane loop of the
      skeletal muscle ryanodine receptor. This is the first mutation in the RyR1 C
      terminal region associated solely with MHS. Although linkage analysis showed
      strong linkage (max LOD, 11.103 at theta = 0.133) between the mutation and MHS in
      the pedigree using the standardized European IVCT phenotyping protocol, 22 MHS
      recombinants were observed. The relationship between the IVCT response and
      genotype was explored and showed that as IVCT diagnostic cut-off points were made
      increasingly stringent, the number of MHS discordants decreased with complete
      concordance between the presence or absence of the C14477T mutation and MHS and
      MH normal phenotypes, respectively, using a cut-off of 1.2 g tension at 2.0 mM
      caffeine and 1.8 g tension at 2.0% halothane. Many MHS pedigrees investigated
      have been excluded from linkage to the RYR1 gene on the basis of a small number
      of recombinants; however, the linkage analysis reported here suggests that other
      recombinant families excluded from linkage to the RYR1 gene may actually
      demonstrate linkage as the number of members tested within the pedigrees
      increases. The high number of discordants observed using the standardized
      diagnostic cut-off points is likely to reflect the presence of a second MHS
      susceptibility locus in the pedigree.

PMID- 10888603
TI  - The most frequent constitutional translocation in humans, the t(11;22)(q23;q11)
      is due to a highly specific alu-mediated recombination.
AB  - The t(11;22) is the most common recurrent non-Robertsonian constitutional
      translocation in humans, having been reported in more than 160 unrelated
      families. Balanced carriers are at risk of having offspring with the derivative
      22 syndrome owing to 3:1 meiotic non-disjunction event. Clinical features of the
      der(22) syndrome include mental retardation, craniofacial abnormalities and
      congenital heart defects. The breakpoints for the t(11;22) translocation have
      been mapped to specific Alu repeats on chromosomes 11 and 22, indicating that
      this event is due to an Alu-Alu recombination. Remarkably, in five samples
      derived from individuals with no apparent common ancestry the der(11) and der(22)
      breakpoints appear to be almost identical at the genomic sequence level. The
      small number of base differences between the samples indicates some variation in
      the position of the breakpoints, although this appears to be quite limited.
      Indeed, the der(11) breakpoints are all located within a region of just 32 bp and
      the der(22) breakpoints within 21 bp. If, as suggested by current data, the
      widespread occurrence of this translocation is due to multiple independent
      events, our results suggest that this particular Alu-Alu recombination is subject
      to an unprecedented degree of selection.

PMID- 10888604
TI  - A candidate gene for psoriasis near HLA-C, HCR (Pg8), is highly polymorphic with
      a disease-associated susceptibility allele.
AB  - A susceptibility gene for psoriasis, a chronic skin disorder, resides in
      chromosome 6p near the HLA-C locus. Sequencing of the region has allowed the
      identification of a new gene, HCR. We found that HCR is highly polymorphic with
      at least 12 coding variants. An association study of the new HCR polymorphisms
      and the previously suggested susceptibility alleles HLA-Cw*0602 and
      corneodesmosin allele 5 (CD*5) with psoriasis revealed a specific HCR variant
      associated with psoriasis susceptibility. However, the HLA-Cw*0602 allele was
      rarer in controls and associated with a stronger relative risk. Association
      analysis did not support CD*5 as a psoriasis susceptibility allele in our sample
      of patients (n = 100) and population-matched controls (n = 93) from an isolated
      population. We found HCR to be overexpressed in keratinocytes of psoriatic
      lesions compared with paired samples of healthy skin. Our results suggest a
      potential role for HCR in the pathogenesis of psoriasis.

PMID- 10888605
TI  - The SCA8 transcript is an antisense RNA to a brain-specific transcript encoding a
      novel actin-binding protein (KLHL1).
AB  - Spinocerebellar ataxia type 8 (SCA8) is a neurodegenerative disorder caused by
      the expansion of a CTG trinucleotide repeat that is transcribed as part of an
      untranslated RNA. As a step towards understanding the molecular pathology of
      SCA8, we have defined the genomic organization of the SCA8 RNA transcripts and
      assembled a 166 kb segment of genomic sequence containing the repeat. The most
      striking feature of the SCA8 transcripts is that the most 5' exon is transcribed
      through the first exon of another gene that is transcribed in the opposite
      orientation. This gene arrangement suggests that the SCA8 transcript is an
      endogenous antisense RNA that overlaps the transcription and translation start
      sites as well as the first splice donor sequence of the sense gene. The sense
      transcript encodes a 748 amino acid protein with a predicted domain structure
      typical of a family of actin-organizing proteins related to the Drosophila Kelch
      gene, and so has been given the name Kelch-like 1 (KLHL1). We have identified the
      full-length cDNA sequence for both the human and mouse KLHLI genes, and have
      elucidated the general genomic organization of the human gene. The predicted open
      reading frame and promoter region are highly conserved, and both genes are
      primarily expressed in specific brain tissues, including the cerebellum, the
      tissue most affected by SCA8. Transfection studies with epitope-tagged KLHL1
      demonstrate that the protein localizes to the cytoplasm, suggesting that it may
      play a role in organizing the actin cytoskeleton of the brain cells in which it
      is expressed.

PMID- 10888606
TI  - Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing
      mouse gonad prior to overt differentiation suggests a role in mammalian sexual
      development.
AB  - The mammalian sex-determining pathway is controlled by the presence or absence of
      SRY expression in the embryonic gonad. Expression of SRY in males is believed to
      initiate a pathway of gene expression resulting in testis development. In the
      absence of SRY, ovary development ensues. Several genes have now been placed in
      this pathway but our understanding of it is far from complete and several
      functional classes of protein appear to be absent. Sex-determining genes
      frequently exhibit sexually dimorphic patterns of expression in the developing
      gonad both before and after overt differentiation of the testis or ovary. In
      order to identify additional sex-determining or gonadal differentiation genes we
      have examined gene expression in the developing gonads of the mouse using cDNA
      microarrays constructed from a normalized urogenital ridge library. We screened
      for genes exhibiting sexually dimorphic patterns of expression in the gonad at
      12.5 and 13.5 days post-coitum, after overt gonad differentiation, by comparing
      complex cDNA probes derived from male and female gonadal tissue at these stages
      on micro-arrays. Using in situ hybridization analysis we show here that two genes
      identified by this screen, protease nexin-1 (Pn-1) and vanin-1 (Vnn1), exhibit
      male-specific expression prior to overt gonadal differentiation and are detected
      in the somatic portion of the developing gonad, suggesting a possible direct link
      to the testis-determining pathway for both genes.

PMID- 10888607
TI  - Rescue of very virulent and mosaic infectious bursal disease virus from cloned
      cDNA: VP2 is not the sole determinant of the very virulent phenotype.
AB  - Many recent outbreaks of infectious bursal disease in commercial chicken flocks
      worldwide are due to the spread of very virulent strains of infectious bursal
      disease virus (vvIBDV). The molecular determinants for the enhanced virulence of
      vvIBDV compared to classical IBDV are unknown. The lack of a reverse genetics
      system to rescue vvIBDV from its cloned cDNA hampers the identification and study
      of these determinants. In this report we describe, for the first time, the rescue
      of vvIBDV from its cloned cDNA. Two plasmids containing a T7 promoter and either
      the full-length A- or B-segment cDNA of vvIBDV (D6948) were cotransfected into
      QM5 cells expressing T7 polymerase. The presence of vvIBDV could be detected
      after passage of the transfection supernatant in either primary bursa cells (in
      vitro) or embryonated eggs (in vivo), but not QM5 cells. Rescued vvIBDV (rD6948)
      appeared to have the same virulence as the parental isolate, D6948. Segment
      reassorted IBDV, in which one of the two genomic segments originated from cDNA of
      classical attenuated IBDV CEF94 and the other from D6948, could also be rescued
      by using this system. Segment-reassorted virus containing the A segment of the
      classical attenuated isolate (CEF94) and the B segment of the very virulent
      isolate (D6948) is not released until 15 h after an in vitro infection. This
      indicates a slightly retarded replication, as the first release of CEF94 is
      already found at 10 h after infection. Next to segment reassortants, we generated
      and analyzed mosaic IBDVs (mIBDVs). In these mIBDVs we replaced the region of
      CEF94 encoding one of the viral proteins (pVP2, VP3, or VP4) by the corresponding
      region of D6948. Analysis of these mIBDV isolates showed that tropism for non-B
      lymphoid cells was exclusively determined by the viral capsid protein VP2.
      However, the very virulent phenotype was not solely determined by this protein,
      since mosaic virus containing VP2 of vvIBDV induced neither morbidity nor
      mortality in young chickens.

PMID- 10888608
TI  - Herpes simplex virus type 1 glycoprotein E domains involved in virus spread and
      disease.
AB  - Herpes simplex virus type 1 (HSV-1) glycoprotein E (gE) functions as an
      immunoglobulin G (IgG) Fc binding protein and is involved in virus spread.
      Previously we studied a gE mutant virus that was impaired for IgG Fc binding but
      intact for spread and another that was normal for both activities. To further
      evaluate the role of gE in spread, two additional mutant viruses were constructed
      by introducing linker insertion mutations either outside the IgG Fc binding
      domain at gE position 210 or within the IgG Fc binding domain at position 380.
      Both mutant viruses were impaired for spread in epidermal cells in vitro;
      however, the 380 mutant virus was significantly more impaired and was as
      defective as gE null virus. gE mutant viruses were inoculated into the murine
      flank to measure epidermal disease at the inoculation site, travel of virus to
      dorsal root ganglia, and spread of virus from ganglia back to skin to produce
      zosteriform lesions. Disease at the inoculation and zosteriform sites was reduced
      for both mutant viruses, but more so for the 380 mutant virus. Moreover, the 380
      mutant virus was highly impaired in its ability to reach the ganglia, as
      demonstrated by virus culture and real-time quantitative PCR. The results
      indicate that the domain surrounding amino acid 380 is important for both spread
      and IgG Fc binding and suggest that this domain is a potential target for
      antiviral therapy or vaccines.

PMID- 10888609
TI  - CD4-independent, CCR5-dependent simian immunodeficiency virus infection and
      chemotaxis of human cells.
AB  - Most simian immunodeficiency virus (SIV), human immunodeficiency virus type 2
      (HIV-2), and HIV-1 infection of host peripheral blood mononuclear cells (PBMCs)
      is CD4 dependent. In some cases, X4 HIV-1 chemotaxis is CD4 independent, and
      cross-species transmission might be facilitated by CD4-independent entry, which
      has been demonstrated for some SIV strains in CD4(-) non-T cells. As expected for
      CCR5-dependent virus, SIV required CD4 on rhesus and pigtail macaque PBMCs for
      infection and chemotaxis. However, SIV induced the chemotaxis of human PBMCs in a
      CD4-independent manner. Furthermore, in contrast to the results of studies using
      transfected human cell lines, SIV did not require CD4 binding to productively
      infect primary human PBMCs. CD4-independent lymphocyte and macrophage infection
      may facilitate cross-species transmission, while reacquisition of CD4 dependence
      may confer a selective advantage for the virus within new host species.

PMID- 10888610
TI  - Effects of palmitoylation of replicase protein nsP1 on alphavirus infection.
AB  - The membrane-associated alphavirus RNA replication complex contains four virus
      encoded subunits, the nonstructural proteins nsP1 to nsP4. Semliki Forest virus
      (SFV) nsP1 is hydrophobically modified by palmitoylation of cysteines 418 to 420.
      Here we show that Sindbis virus nsP1 is also palmitoylated on the same site
      (cysteine 420). When mutations preventing nsP1 palmitoylation were introduced
      into the genomes of these two alphaviruses, the mutant viruses remained viable
      and replicated to high titers, although their growth was slightly delayed. The
      subcellular distribution of palmitoylation-defective nsP1 was altered in the
      mutant: it no longer localized to filopodial extensions, and a fraction of it was
      soluble. The ultrastructure of the alphavirus replication sites appeared normal,
      and the localization of the other nonstructural proteins was unaltered in the
      mutants. In both wild-type- and mutant-virus-infected cells, SFV nsP3 and nsP4
      could be extracted from membranes only by alkaline solutions whereas the nsP2
      membrane association was looser. Thus, the membrane binding properties of the
      alphavirus RNA replication complex were not determined by the palmitoylation of
      nsP1. The nsP1 palmitoylation-defective alphaviruses produced normal plaques in
      several cell types, but failed to give rise to plaques in HeLa cells, although
      they induced normal apoptosis of these cells. The SFV mutant was apathogenic in
      mice: it caused blood viremia, but no infectious virus was detected in the brain.

PMID- 10888611
TI  - Human immunodeficiency virus type 1 virion density is not determined by
      nucleocapsid basic residues.
AB  - The human immunodeficiency virus type 1 (HIV-1) Gag polyprotein is sufficient for
      assembly and release of virion-like particles from the plasma membrane. To
      promote assembly, the Gag polyprotein must polymerize to form a shell that lines
      the inner membrane of nascent virions. Several techniques have been used to
      functionally map the domain required for Gag polymerization (the I domain). Among
      these methods, isopycnic centrifugation has been used under the assumption that
      changes in virion density reflect impairment in Gag-Gag interaction. If virion
      density is determined by efficient Gag-Gag interaction, then mutation of basic
      residues in the nucleocapsid (NC) domain should disrupt virion density, since
      these residues constitute the I domain. However, we have previously shown that
      simultaneous disruption of up to 10 HIV-1 NC basic residues has no obvious effect
      on virion density. To rule out the possibility that HIV-1 NC basic residues other
      than those previously mutated might be important for virion density, mutations
      were introduced at the remaining sites and the ability of these mutations to
      affect Gag-Gag interaction and virion density was analyzed. Included in our
      analysis is a mutant in which all NC basic residues are replaced with alanine.
      Our results show that disruption of HIV-1 NC basic residues has an enormous
      effect on Gag-Gag interaction but only a minimal effect on the density of those
      virions that are still produced. Therefore, the determinants of the I domain and
      of virion density are genetically distinguishable.

PMID- 10888612
TI  - Identification of a gammaherpesvirus selective chemokine binding protein that
      inhibits chemokine action.
AB  - Chemokines are involved in recruitment and activation of hematopoietic cells at
      sites of infection and inflammation. The M3 gene of gammaHV68, a gamma-2
      herpesvirus that infects and establishes a lifelong latent infection and chronic
      vasculitis in mice, encodes an abundant secreted protein during productive
      infection. The M3 gene is located in a region of the genome that is transcribed
      during latency. We report here that the M3 protein is a high-affinity broad
      spectrum chemokine scavenger. The M3 protein bound the CC chemokines human
      regulated upon activation of normal T-cell expressed and secreted (RANTES),
      murine macrophage inflammatory protein 1alpha (MIP-1alpha), and murine monocyte
      chemoattractant protein 1 (MCP-1), as well as the human CXC chemokine interleukin
      8, the murine C chemokine lymphotactin, and the murine CX(3)C chemokine
      fractalkine with high affinity (K(d) = 1. 6 to 18.7 nM). M3 protein chemokine
      binding was selective, since the protein did not bind seven other CXC chemokines
      (K(d) > 1 microM). Furthermore, the M3 protein abolished calcium signaling in
      response to murine MIP-1alpha and murine MCP-1 and not to murine KC or human
      stromal cell-derived factor 1 (SDF-1), consistent with the binding data. The M3
      protein was also capable of blocking the function of human CC and CXC chemokines,
      indicating the potential for therapeutic applications. Since the M3 protein lacks
      homology to known chemokines, chemokine receptors, or chemokine binding proteins,
      these studies suggest a novel herpesvirus mechanism of immune evasion.

PMID- 10888613
TI  - Type 2 cytokines predominate in the human CD4(+) T-lymphocyte response to Epstein
      Barr virus nuclear antigen 1.
AB  - Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that persistently
      infects 85% of the adult population worldwide. In this report, we examine the
      proliferative response and cytokine secretion profile of CD4(+) T lymphocytes
      from a panel of unrelated EBV-positive donors against two EBV latent antigens,
      EBNA1 and EBNA3C. Substantial proliferative responses by CD4(+) lymphocytes were
      demonstrated to both antigens in multiple, randomly selected donors.
      Surprisingly, we observed a striking and consistent difference in cytokine
      response to EBNA1 and EBNA3C. EBNA1-specific CD4(+) T lymphocytes from multiple
      unrelated donors preferentially produced type 2-like cytokines in response to
      antigenic stimulation, while the response to EBNA3C was a characteristic type 1
      response. The implications of these findings for EBV persistence and the
      development of EBV-associated malignancies are discussed.

PMID- 10888614
TI  - Pseudorabies virus glycoprotein M inhibits membrane fusion.
AB  - A transient transfection-fusion assay was established to investigate membrane
      fusion mediated by pseudorabies virus (PrV) glycoproteins. Plasmids expressing
      PrV glycoproteins under control of the immediate-early 1 promoter-enhancer of
      human cytomegalovirus were transfected into rabbit kidney cells, and the extent
      of cell fusion was quantitated 27 to 42 h after transfection. Cotransfection of
      plasmids encoding PrV glycoproteins B (gB), gD, gH, and gL resulted in formation
      of polykaryocytes, as has been shown for homologous proteins of herpes simplex
      virus type 1 (HSV-1) (A. Turner, B. Bruun, T. Minson, and H. Browne, J. Virol.
      72:873-875, 1998). However, in contrast to HSV-1, fusion was also observed when
      the gD-encoding plasmid was omitted, which indicates that PrV gB, gH, and gL are
      sufficient to mediate fusion. Fusogenic activity was enhanced when a carboxy
      terminally truncated version of gB (gB-008) lacking the C-terminal 29 amino acids
      was used instead of wild-type gB. With gB-008, only gH was required in addition
      for fusion. A very rapid and extended fusion was observed after cotransfection of
      plasmids encoding gB-008 and gDH, a hybrid protein consisting of the N-terminal
      271 amino acids of gD fused to the 590 C-terminal amino acids of gH. This protein
      has been shown to substitute for gH, gD, and gL function in the respective viral
      mutants (B. G. Klupp and T. C. Mettenleiter, J. Virol. 73:3014-3022, 1999).
      Cotransfection of plasmids encoding PrV gC, gE, gI, gK, and UL20 with gB-008 and
      gDH had no effect on fusion. However, inclusion of a gM-expressing plasmid
      strongly reduced the extent of fusion. An inhibitory effect was also observed
      after inclusion of plasmids encoding gM homologs of equine herpesvirus 1 or
      infectious laryngotracheitis virus but only in conjunction with expression of the
      gM complex partner, the gN homolog. Inhibition by PrV gM was not limited to PrV
      glycoprotein-mediated fusion but also affected fusion induced by the F protein of
      bovine respiratory syncytial virus, indicating a general mechanism of fusion
      inhibition by gM.

PMID- 10888615
TI  - V2 loop glycosylation of the human immunodeficiency virus type 1 SF162 envelope
      facilitates interaction of this protein with CD4 and CCR5 receptors and protects
      the virus from neutralization by anti-V3 loop and anti-CD4 binding site
      antibodies.
AB  - We examined the role of asparagine-linked glycosylation of the V2 loop of the
      human immunodeficiency virus (HIV) SF162 envelope on viral replication potential
      and neutralization susceptibility. We report that the asparagines located at the
      amino- and carboxy-terminal sites (at positions 154 and 195, respectively), as
      well as within the V2 loop of the SF162 envelope (at position 186), are
      glycosylated during in vitro replication of this virus in human peripheral blood
      mononuclear cells. Our studies indicate that glycosylation of the V2 loop, in
      particular at its base, facilitates the interaction of the HIV envelope with the
      CD4 and CCR5 receptor molecules present on the surface of target cells and
      affects viral replication kinetics in a cell type-dependent manner. In cells
      expressing high numbers of receptor molecules on their surfaces, the SF162
      derived V2 loop-deglycosylated mutant viruses replicate as efficiently as the
      parental SF162 virus, while in cells expressing small numbers of receptor
      molecules, the mutant viruses replicate with markedly reduced efficiency. In
      addition to expanding the viral tropism, V2 loop glycosylation at the three sites
      examined prevents neutralization by anti-CD4 binding site antibodies. In
      contrast, glycosylation at the amino- and carboxy-terminal sites of the V2 loop
      but not within the loop itself offers protection against anti-V3 loop antibodies.
      Thus, the epitopes masked by the sugar molecules present on the three
      glycosylation sites examined are not identical but overlap.

PMID- 10888616
TI  - Effective vaccine for lassa fever.
AB  - Lassa fever has been estimated to cause 5,000 deaths annually in West Africa.
      Recently, war in the zone where Lassa fever is hyperendemic has severely impeded
      control and treatment. Vaccination is the most viable control measure. There is
      no correlation between antibody levels and outcome in human patients, and
      inactivated vaccines produce high titers of antibodies to all viral proteins but
      do not prevent virus replication and death in nonhuman primates. Accordingly, we
      vaccinated 44 macaques with vaccinia virus-expressed Lassa virus structural
      proteins separately and in combination, with the object of inducing a
      predominantly TH1-type immune response. Following Lassa virus challenge, all
      unvaccinated animals died (0% survival). Nine of 10 animals vaccinated with all
      proteins survived (90% survival). Although no animals that received full-length
      glycoprotein alone had a high titer of antibody, 17 of 19 survived challenge
      (88%). In contrast, all animals vaccinated with nucleoprotein developed high
      titers of antibody but 12 of 15 died (20% survival). All animals vaccinated with
      single glycoproteins, G1 or G2, died, but all those that received both single
      glycoproteins (G1 plus G2) at separate sites survived, showing that both
      glycoproteins are independently important in protection. Neither group had
      demonstrable antibody levels prior to challenge. We demonstrate that in primates,
      immune responses to epitopes on both glycoproteins are required to protect
      against lethal challenge with Lassa virus without having untoward side effects
      and that this protection is likely to be primarily cell mediated. We show that an
      effective, safe vaccine against Lassa virus can and should be made and that its
      evaluation for human populations is a matter of humanitarian priority.

PMID- 10888617
TI  - Evidence for nucleic acid binding ability and nucleosome association of Bombyx
      mori nucleopolyhedrovirus BRO proteins.
AB  - The Bombyx mori nucleopolyhedrovirus (BmNPV) genome contains five related members
      of the bro gene family, all of which are actively expressed in infected BmN
      cells. Although their functions are unknown, their amino acid sequences contain a
      motif found in all known viral and prokaryotic single-stranded DNA binding
      proteins. To determine if they bind to nucleic acids, we fractionated the nuclei
      of BmNPV-infected BmN cells using a histone extraction protocol. We detected BRO
      A, BRO-C, and BRO-D in the histone H1 fraction using anti-BRO antibodies.
      Micrococcal nuclease treatment released these BRO proteins from the chromatin
      fraction, suggesting their involvement in nucleosome structures. Chromatographic
      fractionation showed that BRO-A and/or BRO-C interacted with core histones.
      Expression of partial sequences of BRO-A proved that the N-terminal 80 amino acid
      residues were required for DNA binding activity. We also demonstrated that BmNPV
      BRO proteins underwent phosphorylation and ubiquitination followed by proteasome
      degradation, which may explain their distribution in the cytoplasm as well as the
      nucleus. We propose that BRO-A and BRO-C may function as DNA binding proteins
      that influence host DNA replication and/or transcription.

PMID- 10888618
TI  - The human factors YY1 and LSF repress the human immunodeficiency virus type 1
      long terminal repeat via recruitment of histone deacetylase 1.
AB  - Enigmatic mechanisms restore the resting state in activated lymphocytes following
      human immunodeficiency virus type 1 (HIV-1) infection, rarely allowing persistent
      nonproductive infection. We detail a mechanism whereby cellular factors could
      establish virological latency. The transcription factors YY1 and LSF cooperate in
      repression of transcription from the HIV-1 long terminal repeat (LTR). LSF
      recruits YY1 to the LTR via the zinc fingers of YY1. The first two zinc fingers
      were observed to be sufficient for this interaction in vitro. A mutant of LSF
      incapable of binding DNA blocked repression. Like other transcriptional
      repressors, YY1 can function via recruitment of histone deacetylase (HDAC). We
      find that HDAC1 copurifies with the LTR-binding YY1-LSF repressor complex, the
      domain of YY1 that interacts with HDAC1 is required to repress the HIV-1
      promoter, expression of HDAC1 augments repression of the LTR by YY1, and the
      deacetylase inhibitor trichostatin A blocks repression mediated by YY1. This
      novel link between HDAC recruitment and inhibition of HIV-1 expression by YY1 and
      LSF, in the natural context of a viral promoter integrated into chromosomal DNA,
      is the first demonstration of a molecular mechanism of repression of HIV-1. YY1
      and LSF may establish transcriptional and virological latency of HIV, a state
      that has recently been recognized in vivo and has significant implications for
      the long-term treatment of AIDS.

PMID- 10888619
TI  - Antigenic drift in the influenza A virus (H3N2) nucleoprotein and escape from
      recognition by cytotoxic T lymphocytes.
AB  - Viruses exploit different strategies to escape immune surveillance, including the
      introduction of mutations in cytotoxic T-lymphocyte (CTL) epitopes. The sequence
      of these epitopes is critical for their binding to major histocompatibility
      complex (MHC) class I molecules and recognition by specific CTLs, both of which
      interactions may be lost by mutation. Sequence analysis of the nucleoprotein gene
      of influenza A viruses (H3N2) isolated in The Netherlands from 1989 to 1999
      revealed two independent amino acid mutations at the anchor residue of the HLA
      B27-specific CTL epitope SRYWAIRTR (383 to 391). A R384K mutation was found in
      influenza A viruses isolated during the influenza season 1989-1990 but not in
      subsequent seasons. In the influenza season 1993-1994, a novel mutation in the
      same CTL epitope at the same position was introduced. This R384G mutation proved
      to be conserved in all influenza A viruses isolated from 1993 onwards. Both
      mutations R384K and R384G abrogated MHC class I presentation and allowed escape
      from recognition by specific CTLs.

PMID- 10888620
TI  - Human cytomegalovirus infection of placental cytotrophoblasts in vitro and in
      utero: implications for transmission and pathogenesis.
AB  - Human cytomegalovirus (CMV) is the leading cause of prenatal viral infection.
      Affected infants may suffer intrauterine growth retardation and serious
      neurologic impairment. Analysis of spontaneously aborted conceptuses shows that
      CMV infects the placenta before the embryo or fetus. In the human hemochorial
      placenta, maternal blood directly contacts syncytiotrophoblasts that cover
      chorionic villi and cytotrophoblasts that invade uterine vessels, suggesting
      possible routes for CMV transmission. To test this hypothesis, we exposed first
      trimester chorionic villi and isolated cytotrophoblasts to CMV in vitro. In
      chorionic villi, syncytiotrophoblasts did not become infected, although clusters
      of underlying cytotrophoblasts expressed viral proteins. In chorionic villi that
      were infected with CMV in utero, syncytiotrophoblasts were often spared, whereas
      cytotrophoblasts and other cells of the villous core expressed viral proteins.
      Isolated cytotrophoblasts were also permissive for CMV replication in vitro;
      significantly, infection subsequently impaired the cytotrophoblasts' ability to
      differentiate and invade. These results suggest two possible routes of CMV
      transmission to the fetus: (i) across syncytiotrophoblasts with subsequent
      infection of the underlying cytotrophoblasts and (ii) via invasive
      cytotrophoblasts within the uterine wall. Furthermore, the observation that CMV
      infection impairs critical aspects of cytotrophoblast function offers testable
      hypotheses for explaining the deleterious effects of this virus on pregnancy
      outcome.

PMID- 10888621
TI  - Human parainfluenza virus type 3 (PIV3) expressing the hemagglutinin protein of
      measles virus provides a potential method for immunization against measles virus
      and PIV3 in early infancy.
AB  - Recombinant human parainfluenza virus type 3 (PIV3) was used as a vector to
      express the major protective antigen of measles virus, the hemagglutinin (HA)
      glycoprotein, in order to create a bivalent PIV3-measles virus that can be
      administered intranasally. The measles virus HA open reading frame (ORF) was
      inserted as an additional transcriptional unit into the N-P, P-M, or HA
      neuraminidase (HN)-L gene junction of wild-type PIV3 or into the N-P or P-M gene
      junction of an attenuated derivative of PIV3, termed rcp45L. The recombinant PIV3
      (rPIV3) viruses bearing the HA inserts replicated more slowly in vitro than their
      parental viruses but reached comparable peak titers of >/=10(7.5) 50% tissue
      culture infective doses per ml. Each of the wild-type or cold-passaged 45L
      (cp45L) PIV3(HA) chimeric viruses replicated 5- to 10-fold less well than its
      respective parent virus in the upper respiratory tract of hamsters. Thus,
      insertion of the approximately 2-kb ORF itself conferred attenuation, and this
      attenuation was additive to that conferred by the cp45L mutations. The attenuated
      cp45L PIV3(HA) recombinants induced a high level of resistance to replication of
      PIV3 challenge virus in hamsters and induced very high levels of measles virus
      neutralizing antibodies (>1:8,000) that are well in excess of those known to be
      protective in humans. rPIV3s expressing the HA gene in the N-P or P-M junction
      induced about 400-fold more measles virus-neutralizing antibody than did the
      rPIV3 with the HA gene in the HN-L junction, indicating that the N-P or P-M
      junction appears to be the preferred insertion site. Previous studies indicated
      that the PIV3 cp45 virus, a more attenuated version of rcp45L, replicates
      efficiently in the respiratory tract of monkeys and is immunogenic and protective
      even when administered in the presence of very high titers of passively
      transferred PIV3 antibodies (A. P. Durbin, C. J. Cho, W. R. Elkins, L. S. Wyatt,
      B. Moss, and B. R. Murphy, J. Infect. Dis. 179:1345-1351, 1999). This suggests
      that this intranasally administered PIV3(HA) chimeric virus can be used to
      immunize infants with maternally acquired measles virus antibodies in whom the
      current parenterally administered live measles virus vaccine is ineffective.

PMID- 10888622
TI  - Lymphomas and high-level expression of murine leukemia viruses in CFW mice.
AB  - Historically, Swiss Webster mice of the CFW subline, both inbred and random-bred
      stocks, have been considered to have a low spontaneous occurrence of
      hematopoietic system tumors, and previous reports of infectious expression of
      murine leukemia viruses (MuLVs) have been rare and unremarkable. In marked
      contrast, in the present study of CFW mice from one source observed by two
      laboratories over a 2-year period, nearly 60% developed tumors, 85% of which were
      lymphomas, the majority of B-cell origin. All tumors tested expressed ecotropic
      MuLVs, and most expressed mink cell focus-inducing (MCF) MuLVs. Among normal mice
      of weanling to advanced age, over one-half were positive for ecotropic virus in
      tail or lymphoid tissues, and MCF virus was frequently present in lymphoid
      tissue, less often in tail. Patterns of ecotropic proviral integration indicated
      that natural infection occurred by both genetic and exogenous routes. Lymphomas
      were induced in NIH Swiss mice infected as neonates with tissue culture
      propagated MuLVs isolated from normal and tumor tissue of CFW mice.

PMID- 10888623
TI  - Evidence for controlled incorporation of herpes simplex virus type 1 UL26
      protease into capsids.
AB  - Herpes simplex virus type 1 (HSV-1) capsids are initially assembled with an
      internal protein scaffold. The scaffold proteins, encoded by overlapping in-frame
      UL26 and UL26.5 transcripts, are essential for formation and efficient maturation
      of capsids. UL26 encodes an N-terminal protease domain, and its C-terminal
      oligomerization and capsid protein-binding domains are identical to those of
      UL26.5. The UL26 protease cleaves itself, releasing minor scaffold proteins VP24
      and VP21, and the more abundant UL26.5 protein, releasing the major scaffold
      protein VP22a. Unlike VP21 and VP22a, which are removed from capsids upon DNA
      packaging, we demonstrate that VP24 (containing the protease domain) is
      quantitatively retained. To investigate factors controlling UL26 capsid
      incorporation and retention, we used a mutant virus that fails to express UL26.5
      (DeltaICP35 virus). Purified DeltaICP35 B capsids showed altered sucrose gradient
      sedimentation and lacked the dense scaffold core seen in micrographs of wild-type
      B capsids but contained capsid shell proteins in wild-type amounts. Despite C
      terminal sequence identity between UL26 and UL26.5, DeltaICP35 capsids lacking
      UL26.5 products did not contain compensatory high levels of UL26 proteins.
      Therefore, HSV capsids can be maintained and/or assembled on a minimal scaffold
      containing only wild-type levels of UL26 proteins. In contrast to UL26.5,
      increased expression of UL26 did not compensate for the DeltaICP35 growth defect.
      While indirect, these findings are consistent with the view that UL26 products
      are restricted from occupying abundant UL26.5 binding sites within the capsid and
      that this restriction is not controlled by the level of UL26 protein expression.
      Additionally, DeltaICP35 capsids contained an altered complement of DNA cleavage
      and packaging proteins, suggesting a previously unrecognized role for the
      scaffold in this process.

PMID- 10888624
TI  - Cathepsin G, a neutrophil-derived serine protease, increases susceptibility of
      macrophages to acute human immunodeficiency virus type 1 infection.
AB  - Neutrophils dominate acute inflammatory responses that generally evolve into
      chronic inflammatory reactions mediated by monocyte/macrophages and lymphocytes.
      The latter cell types also serve as major targets for human immunodeficiency
      virus type 1 (HIV-1). In this study we have investigated the role of neutrophil
      products, particularly cathepsin G, in HIV infection. Cathepsin G induced
      chemotaxis and production of proinflammatory cytokines by macrophages but not
      CD4(+) T cells. Pretreatment with cathepsin G markedly increased susceptibility
      of macrophages but not CD4(+) T cells to acute HIV-1 infection. When macrophages
      were exposed to pertussis toxin prior to cathepsin G treatment, the cathepsin G
      mediated effect was almost abrogated, suggesting that enhancement of HIV-1
      replication by cathepsin G requires Gi protein-mediated signal transduction.
      Although prolonged exposure to cathepsin G suppressed HIV infection of
      macrophages, serine protease inhibitors, which are exuded from the bloodstream
      later during inflammatory processes, neutralized the inhibitory effect.
      Neutrophil extracts or supernatants from neutrophil cultures, which contain
      cathepsin G, had effects similar to purified cathepsin G. Thus, cathepsin G, and
      possibly other neutrophil-derived serine proteases, may have multiple activities
      in HIV-1 infection of macrophages, including chemoattraction of
      monocyte/macrophages (HIV-1 targets) to inflamed tissue, activation of target
      cells, and increase in their susceptibility to acute HIV-1 infection.

PMID- 10888625
TI  - Sequences of Citrus tristeza virus separated in time and space are essentially
      identical.
AB  - The first Citrus tristeza virus (CTV) genomes completely sequenced (19.3-kb
      positive-sense RNA), from four biologically distinct isolates, are unexpectedly
      divergent in nucleotide sequence (up to 60% divergence). Understanding of whether
      these large sequence differences resulted from recent evolution is important for
      the design of disease management strategies, particularly the use of genetically
      engineered mild (essentially symptomless)-strain cross protection and RNA
      mediated transgenic resistance. The complete sequence of a mild isolate (T30)
      which has been endemic in Florida for about a century was found to be nearly
      identical to the genomic sequence of a mild isolate (T385) from Spain. Moreover,
      samples of sequences of other isolates from distinct geographic locations,
      maintained in different citrus hosts and also separated in time (B252 from
      Taiwan, B272 from Colombia, and B354 from California), were nearly identical to
      the T30 sequence. The sequence differences between these isolates were within or
      near the range of variability of the T30 population. A possible explanation for
      these results is that the parents of isolates T30, T385, B252, B272, and B354
      have a common origin, probably Asia, and have changed little since they were
      dispersed throughout the world by the movement of citrus. Considering that the
      nucleotide divergence among the other known CTV genomes is much greater than
      those expected for strains of the same virus, the remarkable similarity of these
      five isolates indicates a high degree of evolutionary stasis in some CTV
      populations.

PMID- 10888626
TI  - Differences in the ability of human T-cell lymphotropic virus type 1 (HTLV-1) and
      HTLV-2 tax to inhibit p53 function.
AB  - We have analyzed the functional activity of the p53 tumor suppressor in human T
      cell lymphotropic virus type 2 (HTLV-2)-transformed cells. Abundant levels of the
      p53 protein were detected in both HTLV-2A and -2B virus-infected cell lines. The
      p53 was functionally inactive, however, both in transient-transfection assays
      using a p53 reporter plasmid and in induction of p53-responsive genes in response
      to gamma irradiation. We further investigated HTLV-2A Tax and HTLV-2B Tax effects
      on p53 activity. Interestingly, although Tax-2A and -2B inactivate p53, the Tax
      2A protein appears to inhibit p53 function less efficiently than either Tax-1 or
      Tax-2B. In transient-cotransfection assays, Tax-1 and Tax-2B inactivated p53 by
      80%, while Tax2A reduced p53 activity by 20%. In addition, Tax-2A does not
      increase the steady-state level of cellular p53 as well as Tax-1 or -2B does in
      the same assays. Cotransfection assays demonstrated that Tax-2A could efficiently
      transactivate CREB-responsive promoters to the same level as Tax-1 and Tax-2B,
      indicating that the protein was functional. This report provides evidence of the
      first functional difference between the HTLV-2A and -2B subtypes. This comparison
      of the action of HTLV-1 and HTLV-2 Tax proteins on p53 function will provide
      important insights into the mechanism of HTLV transformation.

PMID- 10888627
TI  - Ectodomain of coxsackievirus and adenovirus receptor genetically fused to
      epidermal growth factor mediates adenovirus targeting to epidermal growth factor
      receptor-positive cells.
AB  - Human adenovirus (Ad) is extensively used for a variety of gene therapy
      applications. However, the utility of Ad vectors is limited due to the low
      efficiency of Ad-mediated gene transfer to target cells expressing marginal
      levels of the Ad fiber receptor. Therefore, the present generation of Ad vectors
      could potentially be improved by modification of Ad tropism to target the virus
      to specific organs and tissues. The fact that coxsackievirus and adenovirus
      receptor (CAR) does not play any role in virus internalization, but functions
      merely as the virus attachment site, suggests that the extracellular part of CAR
      might be utilized to block the receptor recognition site on the Ad fiber knob
      domain. We proposed to design bispecific fusion proteins formed by a recombinant
      soluble form of truncated CAR (sCAR) and a targeting ligand. In this study, we
      derived sCAR genetically fused with human epidermal growth factor (EGF) and
      investigated its ability to target Ad infection to the EGF receptor (EGFR)
      overexpressed on cancer cell lines. We have demonstrated that sCAR-EGF protein is
      capable of binding to Ad virions and directing them to EGFR, thereby achieving
      targeted delivery of reporter gene. These results show that sCAR-EGF protein
      possesses the ability to effectively retarget Ad via a non-CAR pathway, with
      enhancement of gene transfer efficiency.

PMID- 10888628
TI  - Evaluation of hepatitis C virus glycoprotein E2 for vaccine design: an
      endoplasmic reticulum-retained recombinant protein is superior to secreted
      recombinant protein and DNA-based vaccine candidates.
AB  - Hepatitis C virus (HCV) is the leading causative agent of blood-borne chronic
      hepatitis and is the target of intensive vaccine research. The virus genome
      encodes a number of structural and nonstructural antigens which could be used in
      a subunit vaccine. The HCV envelope glycoprotein E2 has recently been shown to
      bind CD81 on human cells and therefore is a prime candidate for inclusion in any
      such vaccine. The experiments presented here assessed the optimal form of HCV E2
      antigen from the perspective of antibody generation. The quality of recombinant
      E2 protein was evaluated by both the capacity to bind its putative receptor CD81
      on human cells and the ability to elicit antibodies that inhibited this binding
      (NOB antibodies). We show that truncated E2 proteins expressed in mammalian cells
      bind with high efficiency to human cells and elicit NOB antibodies in guinea pigs
      only when purified from the core-glycosylated intracellular fraction, whereas the
      complex-glycosylated secreted fraction does not bind and elicits no NOB
      antibodies. We also show that carbohydrate moieties are not necessary for E2
      binding to human cells and that only the monomeric nonaggregated fraction can
      bind to CD81. Moreover, comparing recombinant intracellular E2 protein to several
      E2-encoding DNA vaccines in mice, we found that protein immunization is superior
      to DNA in both the quantity and quality of the antibody response elicited.
      Together, our data suggest that to elicit antibodies aimed at blocking HCV
      binding to CD81 on human cells, the antigen of choice is a mammalian cell
      expressed, monomeric E2 protein purified from the intracellular fraction.

PMID- 10888630
TI  - Characterization of an essential RNA secondary structure in the 3' untranslated
      region of the murine coronavirus genome.
AB  - We have previously identified a functionally essential bulged stem-loop in the 3'
      untranslated region of the positive-stranded RNA genome of mouse hepatitis virus.
      This 68-nucleotide structure is composed of six stem segments interrupted by five
      bulges, and its structure, but not its primary sequence, is entirely conserved in
      the related bovine coronavirus. The functional importance of individual stem
      segments of this stem-loop was characterized by genetic analysis using targeted
      RNA recombination. We also examined the effects of stem segment mutations on the
      replication of mouse hepatitis virus defective interfering RNAs. These studies
      were complemented by enzymatic and chemical probing of the stem-loop. Taken
      together, our results confirmed most of the previously proposed structure, but
      they revealed that the terminal loop and an internal loop are larger than
      originally thought. Three of the stem segments were found to be essential for
      viral replication. Further, our results suggest that the stem segment at the base
      of the stem-loop is an alternative base-pairing structure for part of a
      downstream, and partially overlapping, RNA pseudoknot that has recently been
      shown to be necessary for bovine coronavirus replication.

PMID- 10888629
TI  - Use of inhibitors to evaluate coreceptor usage by simian and simian/human
      immunodeficiency viruses and human immunodeficiency virus type 2 in primary
      cells.
AB  - We have used coreceptor-targeted inhibitors to investigate which coreceptors are
      used by human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency
      viruses (SIV), and human immunodeficiency virus type 2 (HIV-2) to enter
      peripheral blood mononuclear cells (PBMC). The inhibitors are TAK-779, which is
      specific for CCR5 and CCR2, aminooxypentane-RANTES, which blocks entry via CCR5
      and CCR3, and AMD3100, which targets CXCR4. We found that for all the HIV-1
      isolates and all but one of the HIV-2 isolates tested, the only relevant
      coreceptors were CCR5 and CXCR4. However, one HIV-2 isolate replicated in human
      PBMC even in the presence of TAK-779 and AMD3100, suggesting that it might use an
      undefined, alternative coreceptor that is expressed in the cells of some
      individuals. SIV(mac)239 and SIV(mac)251 (from macaques) were also able to use an
      alternative coreceptor to enter PBMC from some, but not all, human and macaque
      donors. The replication in human PBMC of SIV(rcm) (from a red-capped mangabey), a
      virus which uses CCR2 but not CCR5 for entry, was blocked by TAK-779, suggesting
      that CCR2 is indeed the paramount coreceptor for this virus in primary cells.

PMID- 10888631
TI  - Quantitation of CD8(+) T-lymphocyte responses to multiple epitopes from simian
      virus 40 (SV40) large T antigen in C57BL/6 mice immunized with SV40, SV40 T
      antigen-transformed cells, or vaccinia virus recombinants expressing full-length
      T antigen or epitope minigenes.
AB  - The cytotoxic T-lymphocyte response to wild-type simian virus 40 large tumor
      antigen (Tag) in C57BL/6 (H2(b)) mice is directed against three H2-D(b)
      restricted epitopes, I, II/III, and V, and one H2-K(b)-restricted epitope, IV.
      Epitopes I, II/III, and IV are immunodominant, while epitope V is
      immunorecessive. We investigated whether this hierarchical response was
      established in vivo or was due to differential expansion in vitro by using direct
      enumeration of CD8(+) T lymphocytes with Tag epitope/major histocompatibility
      complex class I tetramers and intracellular gamma interferon staining. The
      results demonstrate that epitope IV-specific CD8(+) T cells dominated the Tag
      specific response in vivo following immunization with full-length Tag while
      CD8(+) T cells specific for epitopes I and II/III were detected at less than one
      third of this level. The immunorecessive nature of epitope V was apparent in
      vivo, since epitope V-specific CD8(+) T cells were undetectable following
      immunization with full-length Tag. In contrast, high levels of epitope V-specific
      CD8(+) T lymphocytes were recruited in vivo following immunization and boosting
      with a Tag variant in which epitopes I, II/III, and IV had been inactivated. In
      addition, analysis of the T-cell receptor beta (TCRbeta) repertoire of Tag
      epitope-specific CD8(+) cells revealed that multiple TCRbeta variable regions
      were utilized for each epitope except Tag epitope II/III, which was limited to
      TCRbeta10 usage. These results indicate that the hierarchy of Tag epitope
      specific CD8(+) T-cell responses is established in vivo.

PMID- 10888632
TI  - Short- and long-term clinical outcomes in rhesus monkeys inoculated with a highly
      pathogenic chimeric simian/human immunodeficiency virus.
AB  - A highly pathogenic simian/human immunodeficiency virus (SHIV), SHIV(DH12R),
      isolated from a rhesus macaque that had been treated with anti-human CD8
      monoclonal antibody at the time of primary infection with the nonpathogenic,
      molecularly cloned SHIV(DH12), induced marked and rapid CD4(+) T cell loss in all
      rhesus macaques intravenously inoculated with 1.0 50% tissue culture infective
      dose (TCID(50)) to 4.1 x 10(5) TCID(50)s of virus. Animals inoculated with 650
      TCID(50)s of SHIV(DH12R) or more experienced irreversible CD4(+) T lymphocyte
      depletion and developed clinical disease requiring euthanasia between weeks 12
      and 23 postinfection. In contrast, the CD4(+) T-cell numbers in four of five
      monkeys receiving 25 TCID(50)s of SHIV(DH12R) or less stabilized at low levels,
      and these surviving animals produced antibodies capable of neutralizing
      SHIV(DH12R). In the fifth monkey, no recovery from the CD4(+) T cell decline
      occurred, and the animal had to be euthanized. Viral RNA levels, subsequent to
      the initial peak of infection but not at peak viremia, correlated with the virus
      inoculum size and the eventual clinical course. Both initial infection rate
      constants, k, and decay constants, d, were determined, but only the latter were
      statistically correlated to clinical outcome. The attenuating effects of reduced
      inoculum size were also observed when virus was inoculated by the mucosal route.
      Because the uncloned SHIV(DH12R) stock possessed the genetic properties of a
      lentivirus quasispecies, we were able to assess the evolution of the input virus
      swarm in animals surviving the acute infection by monitoring the emergence of
      neutralization escape viral variants.

PMID- 10888633
TI  - CCR8 on human thymocytes functions as a human immunodeficiency virus type 1
      coreceptor.
AB  - To determine whether human immunodeficiency virus type 1 (HIV-1) coreceptors
      besides CXCR4 and CCR5 are involved in HIV-1 infection of the thymus, we focused
      on CCR8, a receptor for the chemokine I-309, because of its high expression in
      the thymus. Similar levels of CCR8 mRNA were detected in immature and mature
      primary human thymocytes. Consistent with this, [(125)I]I-309 was shown to bind
      specifically and with similar affinity to the surface of immature and mature
      human thymocytes. Fusion of human thymocytes with cells expressing HIV-1 X4 or
      X4R5 envelope glycoprotein was inhibited by I-309 in a dose-dependent manner. In
      addition, I-309 partially inhibited productive infection of human thymocytes by
      X4, R5, and X4R5 HIV-1 strains. Our data provide the first evidence that CCR8
      functions as an HIV-1 coreceptor on primary human cells and suggest that CCR8 may
      contribute to HIV-1-induced thymic pathogenesis.

PMID- 10888634
TI  - Effect of the murine leukemia virus extended packaging signal on the rates and
      locations of retroviral recombination.
AB  - Reverse transcriptase (RT) switches templates frequently during DNA synthesis;
      the acceptor template can be the same RNA (intramolecular) or the copackaged RNA
      (intermolecular). Previous results indicated that intramolecular template
      switching occurred far more frequently than intermolecular template switching. We
      hypothesized that intermolecular template-switching events (recombination)
      occurred at a lower efficiency because the copackaged RNA was not accessible to
      the RT. To test our hypothesis, the murine leukemia virus (MLV) extended
      packaging signal (Psi(+)) containing a dimer linkage structure (DLS) was
      relocated from the 5' untranslated region (UTR) to between selectable markers,
      allowing the two viral RNAs to interact closely in this region. It was found that
      the overall maximum recombination rates of vectors with Psi(+) in the 5' UTR or
      Psi(+) between selectable markers were not drastically different. However,
      vectors with Psi(+) located between selectable markers reached a plateau of
      recombination rate at a shorter distance. This suggested a limited enhancement of
      recombination by Psi(+). The locations of the recombination events were also
      examined by using restriction enzyme markers. Recombination occurred in all four
      regions between the selectable markers; the region containing 5' Psi(+) including
      DLS did not undergo more recombination than expected from the size of the region.
      These experiments indicated that although the accessibility of the copackaged RNA
      was important in recombination, other factors existed to limit the number of
      viruses that were capable of undergoing intermolecular template switching. In
      addition, recombinants with multiple template switches were observed at a
      frequency much higher than expected, indicating the presence of high negative
      interference in the MLV-based system. This extends our observation with the
      spleen necrosis virus system and suggests that high negative interference may be
      a common phenomenon in retroviral recombination.

PMID- 10888635
TI  - Cloning and mutagenesis of the murine gammaherpesvirus 68 genome as an infectious
      bacterial artificial chromosome.
AB  - Gammaherpesviruses cause important infections of humans, in particular in
      immunocompromised patients. Recently, murine gammaherpesvirus 68 (MHV-68)
      infection of mice has been developed as a small animal model of gammaherpesvirus
      pathogenesis. Efficient generation of mutants of MHV-68 would significantly
      contribute to the understanding of viral gene functions in virus-host
      interaction, thereby further enhancing the potential of this model. To this end,
      we cloned the MHV-68 genome as a bacterial artificial chromosome (BAC) in
      Escherichia coli. During propagation in E. coli, spontaneous recombination events
      within the internal and terminal repeats of the cloned MHV-68 genome, affecting
      the copy number of the repeats, were occasionally observed. The gene for the
      green fluorescent protein was incorporated into the cloned BAC for identification
      of infected cells. BAC vector sequences were flanked by loxP sites to allow the
      excision of these sequences using recombinase Cre and to allow the generation of
      recombinant viruses with wild-type genome properties. Infectious virus was
      reconstituted from the BAC-cloned MHV-68. Growth of the BAC-derived virus in cell
      culture was indistinguishable from that of wild-type MHV-68. To assess the
      feasibility of mutagenesis of the cloned MHV-68 genome, a mutant virus with a
      deletion of open reading frame 4 was generated. Genetically modified MHV-68 can
      now be analyzed in functionally modified mouse strains to assess the role of
      gammaherpesvirus genes in virus-host interaction and pathogenesis.

PMID- 10888636
TI  - Systemic polyomavirus genome increase and dissemination of capsid-defective
      genomes in mammary gland tumor-bearing mice.
AB  - BALB/c mice that developed tumors 7 to 8 months following neonatal infection by
      polyomavirus (PYV) wild-type strain A2 were characterized with respect to the
      abundance and integrity of the viral genome in the tumors and in 12 nontumorous
      organs. These patterns were compared to those found in tumor-free mice infected
      in parallel. Six mice were analyzed in detail including four sibling females with
      mammary gland tumors. In four of five mammary gland tumors, the viral genome had
      undergone a unique deletion and/or rearrangement. Three tumor-resident genomes
      with an apparently intact large T coding region were present in abundant levels
      in an unintegrated state. Two of these had undergone deletions and rearrangements
      involving the capsid genes and therefore lacked the capacity to produce live
      virus. In the comparative organ survey, the tumors harboring replication
      competent genomes contained by far the highest levels of genomes of any tissue.
      However, the levels of PYV genomes in other organs were elevated by up to 1 to 2
      orders of magnitude compared to those detected in the same organs of tumor-free
      mice. The genomes found in the nontumorous organs had the same rearrangements as
      the genomes residing in the tumors. The original wild-type genome was detected at
      low levels in a few organs, particularly in the kidneys. The data indicate that a
      systemic increase in the level of viral genomes occurred in conjunction with the
      induction of tumors by PYV. The results suggest two novel hypotheses: (i) that
      genomes may spread from the tumors to the usual PYV target tissues and (ii) that
      this dissemination may take place in the absence of capsids, providing an
      important path for a virus to escape from the immune response. This situation may
      offer a useful model for the spread of HPV accompanying HPV-induced oncogenesis.

PMID- 10888637
TI  - Early therapy of vertical human immunodeficiency virus type 1 (HIV-1) infection:
      control of viral replication and absence of persistent HIV-1-specific immune
      responses.
AB  - Studies of potent antiretroviral combination regimens were undertaken in young
      infants to evaluate the potential for long-term suppression of viral replication
      and to evaluate the immune consequences of such therapies. Early combination
      antiretroviral therapy led to a loss of plasma viremia, cultivable virus, and
      labile extrachromosomal replication intermediates. Despite preservation of immune
      function, persistent human immunodeficiency type 1 (HIV-1)-specific immune
      responses were not detected in most infants. The absence of detectable,
      persisting immune responses in most HIV-1-infected infants treated early
      contrasts with what is typically seen in adults who are treated early. These
      results are consistent with the notion that early combination antiretroviral
      therapy of HIV-1-infected infants allows the long-term suppression of viral
      replication.

PMID- 10888638
TI  - Genetic diversity among Lassa virus strains.
AB  - The arenavirus Lassa virus causes Lassa fever, a viral hemorrhagic fever that is
      endemic in the countries of Nigeria, Sierra Leone, Liberia, and Guinea and
      perhaps elsewhere in West Africa. To determine the degree of genetic diversity
      among Lassa virus strains, partial nucleoprotein (NP) gene sequences were
      obtained from 54 strains and analyzed. Phylogenetic analyses showed that Lassa
      viruses comprise four lineages, three of which are found in Nigeria and the
      fourth in Guinea, Liberia, and Sierra Leone. Overall strain variation in the
      partial NP gene sequence was found to be as high as 27% at the nucleotide level
      and 15% at the amino acid level. Genetic distance among Lassa strains was found
      to correlate with geographic distance rather than time, and no evidence of a
      "molecular clock" was found. A method for amplifying and cloning full-length
      arenavirus S RNAs was developed and used to obtain the complete NP and
      glycoprotein gene (GP1 and GP2) sequences for two representative Nigerian strains
      of Lassa virus. Comparison of full-length gene sequences for four Lassa virus
      strains representing the four lineages showed that the NP gene (up to 23.8%
      nucleotide difference and 12.0% amino acid difference) is more variable than the
      glycoprotein genes. Although the evolutionary order of descent within Lassa virus
      strains was not completely resolved, the phylogenetic analyses of full-length NP,
      GP1, and GP2 gene sequences suggested that Nigerian strains of Lassa virus were
      ancestral to strains from Guinea, Liberia, and Sierra Leone. Compared to the New
      World arenaviruses, Lassa and the other Old World arenaviruses have either
      undergone a shorter period of diverisification or are evolving at a slower rate.
      This study represents the first large-scale examination of Lassa virus genetic
      variation.

PMID- 10888639
TI  - Cooperation of multiple CCR5 coreceptors is required for infections by human
      immunodeficiency virus type 1.
AB  - In addition to the primary cell surface receptor CD4, CCR5 or another coreceptor
      is necessary for infections by human immunodeficiency virus type 1 (HIV-1), yet
      the mechanisms of coreceptor function and their stoichiometries in the infection
      pathway remain substantially unknown. To address these issues, we studied the
      effects of CCR5 concentrations on HIV-1 infections using wild-type CCR5 and two
      attenuated mutant CCR5s, one with the mutation Y14N at a critical tyrosine
      sulfation site in the amino terminus and one with the mutation G163R in
      extracellular loop 2. The Y14N mutation converted a YYT sequence at positions 14
      to 16 to an NYT consensus site for N-linked glycosylation, and the mutant protein
      was shown to be glycosylated at that position. The relationships between HIV-1
      infectivity values and CCR5 concentrations took the form of sigmoidal (S-shaped)
      curves, which were dramatically altered in different ways by these mutations.
      Both mutations shifted the curves by factors of approximately 30- to 150-fold
      along the CCR5 concentration axis, consistent with evidence that they reduce
      affinities of virus for the coreceptor. In addition, the Y14N mutation
      specifically reduced the maximum efficiencies of infection that could be obtained
      at saturating CCR5 concentrations. The sigmoidal curves for all R5 HIV-1 isolates
      were quantitatively consistent with a simple mathematical model, implying that
      CCR5s reversibly associate with cell surface HIV-1 in a concentration-dependent
      manner, that approximately four to six CCR5s assemble around the virus to form a
      complex needed for infection, and that both mutations inhibit assembly of this
      complex but only the Y14N mutation also significantly reduces its ability to
      successfully mediate HIV-1 infections. Although several alternative models would
      be compatible with our data, a common feature of these alternatives is the
      cooperation of multiple CCR5s in the HIV-1 infection pathway. This cooperativity
      will need to be considered in future studies to address in detail the mechanism
      of CCR5-mediated HIV-1 membrane fusion.

PMID- 10888640
TI  - Murine gammaherpesvirus 68 cyclin D homologue is required for efficient
      reactivation from latency.
AB  - Murine gammaherpesvirus 68 (MHV68) is a gammaherpesvirus that was first isolated
      from murid rodents. MHV68 establishes a latent infection in the spleen and other
      lymphoid organs. Several gammaherpesviruses, including herpesvirus saimiri, human
      herpesvirus 8, and MHV68, encode proteins with extensive homology to the D-type
      cyclins. To study the function of the cyclin homologue, a recombinant MHV68 has
      been constructed that lacks the cyclin homologue and expresses beta-galactosidase
      as a marker (MHV68(cy-)). MHV68(cy-) grows in vitro with kinetics and to titers
      similar to those of the wild type. BALB/c mice infected with mixtures of
      equivalent amounts of the wild type and MHV68(cy-) show deficient growth of the
      MHV68(cy-) in an acute infection. Infection of SCID mice with virus mixtures also
      showed decreased MHV68(cy-) virus growth, indicating that the deficiency is not
      mediated by T or B cells. Although mice infected with mixtures containing 100
      times as much MHV68(cy-) had greater splenic titers of the mutant virus than wild
      type virus in acute infection, at 28 days postinfection splenocytes from these
      mice reactivated primarily wild-type virus. Quantitative PCR data indicate that
      equivalent genomes were present in the latent state. Reinsertion of the cyclin
      homologue into the cyclin-deleted virus restored the wild-type phenotype. These
      results indicate that the MHV68 cyclin D homologue mediates important functions
      in the acute infection and is required for efficient reactivation from latency.

PMID- 10888641
TI  - Cell type-specific enhancement of hepatitis C virus internal ribosome entry site
      directed translation due to 5' nontranslated region substitutions selected during
      passage of virus in lymphoblastoid cells.
AB  - Low-level replication of hepatitis C virus (HCV) in cultured lymphoblastoid cells
      inoculated with H77 serum inoculum led to the appearance of new virus variants
      containing identical substitutions at three sites within the viral 5'
      nontranslated RNA (5'NTR): G(107)-->A, C(204)-->A, and G(243)-->A (N. Nakajima,
      M. Hijikata, H. Yoshikura, and Y. K. Shimizu, J. Virol. 70:3325-3329, 1996).
      These results suggest that virus with this 5'NTR sequence may have a greater
      capacity for replication in such cells, possibly due to more efficient cap
      independent translation, since these nucleotide substitutions reside within the
      viral internal ribosome entry site (IRES). To test this hypothesis, we examined
      the translation of dicistronic RNAs containing upstream and downstream reporter
      sequences (Renilla and firefly luciferases, respectively) separated by IRES
      sequences containing different combinations of these substitutions. The activity
      of the IRES was assessed by determining the relative firefly and Renilla
      luciferase activities expressed in transfected cells. Compared with the IRES
      present in the dominant H77 quasispecies, an IRES containing all three nucleotide
      substitutions had significantly greater translational activity in three of five
      human lymphoblastoid cell lines (Raji, Bjab, and Molt4 but not Jurkat or HPBMa10
      2 cells). In contrast, these substitutions did not enhance IRES activity in cell
      lines derived from monocytes or granulocytes (HL-60, KG-1, or THP-1) or
      hepatocytes (Huh-7) or in cell-free translation assays carried out with rabbit
      reticulocyte lysates. Each of the three substitutions was required for maximally
      increased translational activity in the lymphoblastoid cells. The 2- to 2.5-fold
      increase in translation observed with the modified IRES sequence may facilitate
      the replication of HCV, possibly accounting for differences in quasispecies
      variants recovered from liver tissue and peripheral blood mononuclear cells of
      the same patient.

PMID- 10888642
TI  - The virus-specific and allospecific cytotoxic T-lymphocyte response to
      lymphocytic choriomeningitis virus is modified in a subpopulation of CD8(+) T
      cells coexpressing the inhibitory major histocompatibility complex class I
      receptor Ly49G2.
AB  - The role of negatively signaling NK cell receptors of the Ly49 family on the
      specificity of the acute CD8(+) cytotoxic T-lymphocyte (CTL) response was
      investigated in lymphocytic choriomeningitis virus (LCMV)-infected C57BL/6 mice.
      Activated CD8(+) T cells coexpressing Ly49G2 expanded during LCMV infection, and
      T-cell receptor analyses by flow cytometry and CDR3 spectratyping revealed a
      unique polyclonal T-cell population in the Ly49G2(+) fraction. These cells lysed
      syngeneic targets infected with LCMV or coated with two of three LCMV
      immunodominant peptides examined. Transfection of these sensitive targets with
      H2D(d), a ligand for Ly49G2, inhibited lysis. This was reversed by antibody to
      Ly49G2, indicating effective negative signaling. LCMV characteristically induces
      an anti-H2(d) allospecific T-cell response that includes T-cell clones cross
      reactive between allogeneic and LCMV-infected syngeneic targets. The CD8(+)
      Ly49G2(+) population mediated no allospecific killing, nor was any NK-like
      killing observed against YAC-1 cells. This study shows that CD8(+) Ly49G2(+)
      cells participate in the virus-induced CTL response but lyse a more restricted
      range of targets than the rest of the virus-induced CTL population.

PMID- 10888643
TI  - The interaction of vpr with uracil DNA glycosylase modulates the human
      immunodeficiency virus type 1 In vivo mutation rate.
AB  - The Vpr protein of human immunodeficiency virus type 1 (HIV-1) influences the in
      vivo mutation rate of the virus. Since Vpr interacts with a cellular protein
      implicated in the DNA repair process, uracil DNA glycosylase (UNG), we have
      explored the contribution of this interaction to the mutation rate of HIV-1.
      Single-amino-acid variants of Vpr were characterized for their differential UNG
      binding properties and used to trans complement vpr null mutant HIV-1. A striking
      correlation was established between the abilities of Vpr to interact with UNG and
      to influence the HIV-1 mutation rate. We demonstrate that Vpr incorporation into
      virus particles is required to influence the in vivo mutation rate and to mediate
      virion packaging of the nuclear form of UNG. The recruitment of UNG into virions
      indicates a mechanism for how Vpr can influence reverse transcription accuracy.
      Our data suggest that distinct mechanisms evolved in primate and nonprimate
      lentiviruses to reconcile uracil misincorporation into lentiviral DNA.

PMID- 10888644
TI  - DNA vaccines encoding viral glycoproteins induce nonspecific immunity and Mx
      protein synthesis in fish.
AB  - Protective immunity by vaccination with plasmid DNA encoding a viral glycoprotein
      (G) has long been assumed to result from the induction of a specific immune
      response. We report here that the initial protection may be due to the induction
      of alpha/beta interferon, with long-term protection due to a specific response to
      the encoded viral G. DNA vaccines encoding the Gs of three serologically
      unrelated fish rhabdoviruses were used to vaccinate rainbow trout against a
      lethal challenge with infectious hematopoietic necrosis virus (IHNV). All three
      vaccines, each encoding the G gene of either IHNV (IHNV-G), snakehead rhabdovirus
      (SHRV) (SHRV-G), or spring viremia of carp virus (SVCV) (SVCV-G), elicited
      protective immunity against IHNV. Vaccinated fish were challenged at 30 or 70
      days postvaccination with lethal doses of IHNV. At 30 days postvaccination, only
      5% of fish that had received any of the G vaccines died, whereas more than 50% of
      the control fish succumbed to virus challenge. When fish were vaccinated and
      challenged at 70 days postvaccination, only 12% of the IHNV-G-vaccinated fish
      died compared to 68% for the SHRV-G- and 76% for the SVCV-G-vaccinated fish.
      Assays for trout Mx protein, an indicator of alpha/beta interferon induction,
      showed that only fish vaccinated with a G-containing plasmid produced high levels
      of Mx protein in the kidneys and liver. Interestingly, at day 7 after virus
      challenge, all of the fish vaccinated with the IHNV-G plasmid were negative for
      Mx, but the SHRV-G- and SVCV-G-vaccinated fish still showed detectable levels of
      Mx. These results suggest that DNA vaccines in fish induce an early, nonspecific
      antiviral protection mediated by an alpha/beta interferon and, later, a specific
      immune response.

PMID- 10888645
TI  - Synthesis of virus-specific high-mobility DNA after temperature upshift of SC-1
      cells chronically infected with moloney murine leukemia virus mutant ts1.
AB  - Premature termination products of reverse transcription that consist physically
      of viral minus-sense single-stranded DNA that is shorter than one long terminal
      repeat and partial DNA duplexes are dramatically increased in the central nervous
      system (CNS) of FVB/N mice that are infected by ts1, a temperature-sensitive
      mutant of Moloney murine leukemia virus. Due to their migration in agarose gels,
      these incomplete physical forms of DNA have been designated high-mobility (HM)
      DNA. In non-CNS tissues, the level of HM DNA is either low or not detectable. In
      order to determine the conditions that are necessary for the synthesis of HM DNA
      in vivo, we have characterized the physical forms of HM DNA that were synthesized
      in vitro in chronically infected SC-1 cells after temperature upshift. At the
      permissive temperature of 34 degrees C, the chronically infected SC-1 cells did
      not synthesize HM DNA. After temperature upshift of the cultured cells from 34 to
      37 degrees C, the chronically infected SC-1 cells developed extremely high levels
      of HM DNA. Following temperature downshift of the cultured cells from 37 to 34
      degrees C, a decrease in the level of HM DNA and an increase in the level of
      unintegrated linear proviral DNA occurred simultaneously. These results suggested
      that the accumulation of HM DNA both in vitro and in vivo may be the result of
      superinfection.

PMID- 10888646
TI  - Efficient translation of rotavirus mRNA requires simultaneous interaction of NSP3
      with the eukaryotic translation initiation factor eIF4G and the mRNA 3' end.
AB  - In contrast to the vast majority of cellular proteins, rotavirus proteins are
      translated from capped but nonpolyadenylated mRNAs. The viral nonstructural
      protein NSP3 specifically binds the 3'-end consensus sequence of viral mRNAs and
      interacts with the eukaryotic translation initiation factor eIF4G. Here we show
      that expression of NSP3 in mammalian cells allows the efficient translation of
      virus-like mRNA. A synergistic effect between the cap structure and the 3' end of
      rotavirus mRNA was observed in NSP3-expressing cells. The enhancement of viral
      mRNA translation by NSP3 was also observed in a rabbit reticulocyte lysate
      translation system supplemented with recombinant NSP3. The use of NSP3 mutants
      indicates that its RNA- and eIF4G-binding domains are both required to enhance
      the translation of viral mRNA. The results reported here show that NSP3 forms a
      link between viral mRNA and the cellular translation machinery and hence is a
      functional analogue of cellular poly(A)-binding protein.

PMID- 10888647
TI  - The chicken anemia virus-derived protein apoptin requires activation of caspases
      for induction of apoptosis in human tumor cells.
AB  - The chicken anemia virus protein Apoptin has been shown to induce apoptosis in a
      large number of transformed and tumor cell lines, but not in primary cells.
      Whereas many other apoptotic stimuli (e.g., many chemotherapeutic agents and
      radiation) require functional p53 and are inhibited by Bcl-2, Apoptin acts
      independently of p53, and its activity is enhanced by Bcl-2. Here we study the
      involvement of caspases, an important component of the apoptotic machinery
      present in mammalian cells. Using a specific antibody, active caspase-3 was
      detected in cells expressing Apoptin and undergoing apoptosis. Although Apoptin
      activity was not affected by CrmA, p35 did inhibit Apoptin-induced apoptosis, as
      determined by nuclear morphology. Cells expressing both Apoptin and p35 showed
      only a slight change in nuclear morphology. However, in most of these cells,
      cytochrome c is still released and the mitochondria are not stained by CMX-Ros,
      indicating a drop in mitochondrial membrane potential. These results imply that
      although the final apoptotic events are blocked by p35, parts of the upstream
      apoptotic pathway that affect mitochondria are already activated by Apoptin.
      Taken together, these data show that the viral protein Apoptin employs cellular
      apoptotic factors for induction of apoptosis. Although activation of upstream
      caspases is not required, activation of caspase-3 and possibly also other
      downstream caspases is essential for rapid Apoptin-induced apoptosis.

PMID- 10888648
TI  - A hypothesis for DNA viruses as the origin of eukaryotic replication proteins.
AB  - The eukaryotic replicative DNA polymerases are similar to those of large DNA
      viruses of eukaryotic and bacterial T4 phages but not to those of eubacteria. We
      develop and examine the hypothesis that DNA virus replication proteins gave rise
      to those of eukaryotes during evolution. We chose the DNA polymerase from
      phycodnavirus (which infects microalgae) as the basis of this analysis, as it
      represents a virus of a primitive eukaryote. We show that it has significant
      similarity with replicative DNA polymerases of eukaryotes and certain of their
      large DNA viruses. Sequence alignment confirms this similarity and establishes
      the presence of highly conserved domains in the polymerase amino terminus.
      Subsequent reconstruction of a phylogenetic tree indicates that these algal viral
      DNA polymerases are near the root of the clade containing all eukaryotic DNA
      polymerase delta members but that this clade does not contain the polymerases of
      other DNA viruses. We consider arguments for the polarity of this relationship
      and present the hypothesis that the replication genes of DNA viruses gave rise to
      those of eukaryotes and not the reverse direction.

PMID- 10888649
TI  - The first step of adenovirus type 2 disassembly occurs at the cell surface,
      independently of endocytosis and escape to the cytosol.
AB  - Disassembly is a key event of virus entry into cells. Here, we have investigated
      cellular requirements for the first step of adenovirus type 2 (Ad2) disassembly,
      the release of the fibers. Although fiber release coincides temporally with virus
      uptake, fiber release is not required for Ad2 endocytosis. It is, however,
      inhibited by actin-disrupting agents or soluble RGD peptides, which interfere
      with integrin-dependent endocytosis of Ad2. Fiber release occurs at the cell
      surface. Actin stabilization with jasplakinolide blocks Ad2 entry at extended
      cell surface invaginations and efficiently promotes fiber release, indicating
      that fiber release and virus endocytosis are independent events. Fiber release is
      not sufficient for Ad2 escape from endosomes, since inhibition of protein kinase
      C (PKC) prevents Ad2 escape from endosomes but does not affect virus
      internalization or fiber release. PKC-inhibited cells accumulate Ad2 in small
      vesicles near the cell periphery, indicating that PKC is also required for
      membrane trafficking of virus. Taken together, our data show that fiber release
      from incoming Ad2 requires integrins and filamentous actin. Together with correct
      subcellular transport of Ad2-containing endosomes, fiber release is essential for
      efficient delivery of virus to the cytosol. We speculate that fiber release at
      the surface might extend the host range of Ad2 since it is associated with the
      separation of a small fraction of incoming virus from the target cells.

PMID- 10888650
TI  - Conserved and exposed epitopes on intact, native, primary human immunodeficiency
      virus type 1 virions of group M.
AB  - We have examined the exposure and conservation of antigenic epitopes on the
      surface envelope glycoproteins (gp120 and gp41) of 26 intact, native, primary
      human immunodeficiency virus type 1 (HIV-1) group M virions of clades A to H. For
      this, 47 monoclonal antibodies (MAbs) derived from HIV-1-infected patients were
      used which were directed at epitopes of gp120 (specifically V2, C2, V3, the CD4
      binding domain [CD4bd], and C5) and epitopes of gp41 (clusters I and II). Of the
      five regions within gp120 examined, MAbs bound best to epitopes in the V3 and C5
      regions. Only moderate to weak binding was observed by most MAbs to epitopes in
      the V2, C2, and CD4bd regions. Two anti-gp41 cluster I MAbs targeted to a region
      near the tip of the hydrophilic immunodominant domain bound strongly to >90% of
      isolates tested. On the other hand, binding of anti-gp41 cluster II MAbs was poor
      to moderate at best. Binding was dependent on conformational as well as linear
      structures on the envelope proteins of the virions. Further studies of
      neutralization demonstrated that MAbs that bound to virions did not always
      neutralize but all MAbs that neutralized bound to the homologous virus. This
      study demonstrates that epitopes in the V3 and C5 regions of gp120 and in the
      cluster I region of gp41 are well exposed on the surface of intact, native,
      primary HIV-1 isolates and that cross-reactive epitopes in these regions are
      shared by many viruses from clades A to H. However, only a limited number of MAbs
      to these epitopes on the surface of HIV-1 isolates can neutralize primary
      isolates.

PMID- 10888651
TI  - The human cytomegalovirus IE86 protein can block cell cycle progression after
      inducing transition into the S phase of permissive cells.
AB  - Human cytomegalovirus (HCMV) infection of permissive cells has been reported to
      induce a cell cycle halt. One or more viral proteins may be involved in halting
      progression at different stages of the cell cycle. We investigated how HCMV
      infection, and specifically IE86 protein expression, affects the cell cycles of
      permissive and nonpermissive cells. We used a recombinant virus that expresses
      the green fluorescent protein (GFP) to determine the effects of HCMV on the cell
      cycle of permissive cells. Fluorescence by GFP allowed us to select for only
      productively infected cells. Replication-defective adenovirus vectors expressing
      the IE72 or IE86 protein were also used to efficiently transduce 95% or more of
      the cells. The adenovirus-expressed IE86 protein was determined to be functional
      by demonstrating negative autoregulation of the major immediate-early promoter
      and activation of an early viral promoter in the context of the viral genome. To
      eliminate adenovirus protein effects, plasmids expressing GFP for fluorescent
      selection of only transfected cells and wild-type IE86 protein or a mutant IE86
      protein were tested in permissive and nonpermissive cells. HCMV infection induced
      the entry of U373 cells into the S phase. All permissive cells infected with HCMV
      were blocked in cell cycle progression and could not divide. After either
      transduction or transfection and IE86 protein expression, the number of all
      permissive or nonpermissive cell types in the S phase increased significantly,
      but the cells could no longer divide. The IE72 protein did not have a significant
      effect on the S phase. Since IE86 protein inhibits cell cycle progression, the
      IE2 gene in a human fibroblast IE86 protein-expressing cell line was sequenced.
      The IE86 protein in these retrovirus-transduced cells has mutations in a critical
      region of the viral protein. The locations of the mutations and the function of
      the IE86 protein in controlling cell cycle progression are discussed.

PMID- 10888652
TI  - The karyophilic properties of human immunodeficiency virus type 1 integrase are
      not required for nuclear import of proviral DNA.
AB  - Integrase (IN) is a key component of the preintegration nucleoprotein complex
      (PIC), which transports the retroviral genome from the cytoplasm to the nucleus
      of newly infected cells. Retroviral IN proteins have intrinsic karyophilic
      properties, which for human immunodeficiency virus type 1 (HIV-1) are currently
      attributed to regions that display sequence homology to previously characterized
      nuclear localization signals. We asked here whether the karyophilic properties of
      HIV-1 IN are involved in the nuclear import of PIC. We mutated three conserved
      basic regions in the C-terminal domain of IN and analyzed the effects of
      mutations on subcellular localization of the protein, viral particle composition,
      IN dimerization within virions, and infectivity. Alteration of two sequences
      caused the loss of nuclear accumulation of IN and drastically reduced the
      capacity of the protein to multimerize. Mutation of the most C-terminal sequence
      had no effect on the subcellular localization and dimerization of IN.
      Nevertheless, conservation of all three sequences was required for viral
      infectivity. Despite the perturbation of IN subcellular localization, all mutant
      viruses displayed normal reverse transcription and nuclear transport of PICs in
      newly infected cells. The replicative defect was instead at the level of
      integration, for which all mutants were markedly affected in vivo. Besides
      reinforcing the association between dimerization of IN and nuclear accumulation
      of the enzyme, our data demonstrate that subcellular localization of IN alone
      cannot predict the fate of the PICs.

PMID- 10888653
TI  - Mature dendritic cells infected with herpes simplex virus type 1 exhibit
      inhibited T-cell stimulatory capacity.
AB  - Mature dendritic cells (DC) are the most potent antigen-presenting cells within
      the entire immune system. Interference with the function of these cells therefore
      constitutes a very powerful mechanism for viruses to escape immune responses.
      Several members of the Herpesviridae family have provided examples of such escape
      strategies, including interference with antigen presentation and production of
      homologous cytokines. In this study we investigated the infection of mature DC
      with herpes simplex virus type 1 (HSV-1) and the way in which infection alters
      the phenotype and function of mature DC. Interestingly, the T-cell-stimulatory
      capacity of these DC was strongly impaired. Furthermore, we demonstrated that HSV
      1 leads to the specific degradation of CD83, a cell surface molecule which is
      specifically upregulated during DC maturation. These data indicate that HSV-1 has
      developed yet another novel mechanism to escape immune responses.

PMID- 10888654
TI  - Effects of truncation of the carboxy terminus of pseudorabies virus glycoprotein
      B on infectivity.
AB  - Glycoproteins homologous to the type I membrane glycoprotein B (gB) of herpes
      simplex virus 1 (HSV-1) are the most highly conserved glycoproteins within the
      family Herpesviridae and are present in members of each herpesvirus subfamily. In
      the alphaherpesvirus pseudorabies virus (PrV), gB is required for entry into
      target cells and for direct viral cell-to-cell spread. These processes, though
      related, appear to be distinct, and thus it was interesting to analyze whether
      they require different functions of gB. To this end, we established cell lines
      stably expressing different carboxy-terminally truncated versions of PrV gB by
      deleting either (i) one predicted intracytoplasmic alpha-helical domain
      encompassing putative YQRL and dileucine internalization signals, (ii) two
      predicted intracytoplasmic alpha-helical domains, (iii) the complete
      intracytoplasmic domain, or (iv) the intracytoplasmic domain and the
      transmembrane anchor region. Confocal laser scanning microscopy showed that gB
      derivatives lacking at least the last 29 amino acids (aa) localize close to the
      plasma membrane, while the full-length protein accumulates in intracellular
      aggregations. Trans-complementation studies with a gB-deleted PrV (PrV-gB(-))
      demonstrated that the 29-aa truncated form lacking the putative internalization
      signals and the C-terminal alpha-helical domain (gB-008) was efficiently
      incorporated into PrV-gB(-) virions and efficiently complemented infectivity and
      cell-to-cell spread. Moreover, gB-008 exhibited an enhanced fusogenic activity.
      In contrast, gB proteins lacking both alpha-helical domains (gB-007), the
      complete intracytoplasmic domain, or the intracytoplasmic domain and
      transmembrane anchor were only inefficiently or not at all incorporated into PrV
      gB(-) virions and did not complement infectivity. However, gB-007 was able to
      mediate cell-to-cell spread of PrV-gB(-). Similar phenotypes were observed when
      virus recombinants expressing gB-008 or gB-007, respectively, instead of wild
      type gB were isolated and analyzed. Thus, our data show that internalization of
      gB is not required for gB incorporation into virions nor for its function in
      either entry or cell-to-cell spread. Moreover, they indicate different
      requirements for gB in these membrane fusion processes.

PMID- 10888655
TI  - Release of vasoactive cytokines by antibody-enhanced dengue virus infection of a
      human mast cell/basophil line.
AB  - We report here the first demonstration of dengue virus infection and vasoactive
      cytokine response of a cell of the mast cell/basophil lineage. Infection of KU812
      cells was dependent on dengue-specific antibody and gave rise to infectious
      virions. This antibody-enhanced dengue virus infection triggered a four- to
      fivefold increase in the release of interleukin-1beta (IL-1beta) and a modest
      increase for IL-6 but not for an alternate cytokine, granulocyte-macrophage
      colony-stimulating factor. The results suggest a potential role for mast
      cells/basophils in the pathogenesis of dengue virus-induced disease.

PMID- 10888656
TI  - Effect of coexpression of interleukin-2 by recombinant respiratory syncytial
      virus on virus replication, immunogenicity, and production of other cytokines.
AB  - We constructed rRSV/mIL-2, a recombinant respiratory syncytial virus (rRSV)
      containing the coding sequence of murine interleukin-2 (mIL-2) in a transcription
      cassette inserted into the G-F intergenic region. The recovered virus (rRSV/mIL
      2) expressed high levels (up to 2.8 microg/ml) of mIL-2 in cell culture.
      Replication of rRSV/mIL-2 in vitro was reduced up to 13.6-fold from that of wild
      type (wt) rRSV, an effect that was due to the presence of the foreign insert but
      was not specific to mIL-2. Replication of the rRSV/mIL-2 virus in the upper and
      lower respiratory tracts of BALB/c mice was reduced up to 6.3-fold, an effect
      that was specific to mIL-2. The antibody response, including the levels of RSV
      specific serum immunoglobulin G1 (IgG1), IgG2a, IgA, and total IgG, and the level
      of protective efficacy against wt RSV challenge were not significantly different
      from those of wt rRSV. Analysis of total pulmonary cytokine mRNA isolated 1 and 4
      days following infection with rRSV/mIL-2 revealed elevated levels of mRNA for IL
      2, gamma interferon (IFN-gamma), IL-4, IL-5, IL-6, IL-10, IL-13, and IL-12 p40
      compared to those for wt rRSV. Flow cytometry of total pulmonary mononuclear
      cells isolated 10 days following infection with rRSV/mIL-2 revealed increased
      levels of CD4(+) T lymphocytes expressing either IFN-gamma or IL-4 compared to
      those of wt rRSV. These elevations in cytokine mRNA or cytokine-expressing CD4(+)
      cells relative to those of wt rRSV-primed animals were not observed following
      challenge with wt RSV on day 28. Thus, the expression of mIL-2 by rRSV was
      associated with a modest attenuation of virus growth in vivo, induction of serum
      antibodies at levels comparable to that of wt rRSV, and transient increases in
      both the Th1 and Th2 CD4(+) lymphocytes and cytokine mRNAs compared to those of
      wt rRSV.

PMID- 10888657
TI  - Characterization of a macaque recombinant monoclonal antibody that binds to a CD4
      induced epitope and neutralizes simian immunodeficiency virus.
AB  - A potent neutralizing Fab fragment from a long-term survivor of simian
      immunodeficiency virus (SIVsm) infection was used to construct a recombinant
      macaque immunoglobulin G1kappa (IgG1kappa) molecule, designated IgG1-201. A
      Chinese hamster ovary cell line expressing IgG1-201 was derived by stable
      transfection and optimized for antibody secretion by methotrexate selection and
      dihydrofolate reductase gene amplification. IgG1-201 effectively neutralized the
      homologous, molecularly cloned SIVsmH4 virus but had no activity against the
      heterologous SIVmac251/BK28 virus. The previously characterized, neutralization
      resistant SIVsmE543-3 virus was also not neutralized by IgG1-201. Binding to
      SIVsmH4 gp120 was enhanced in the presence of recombinant soluble CD4, suggesting
      that IgG1-201 bound a CD4-induced epitope. IgG1-201 immunoprecipitated the
      SIVsmH4 but not the SIVsmE543-3 envelope despite a close relationship between
      these two clones. Immunoprecipitation of a panel of SIVsmH4/SIVsmE543-3 chimeric
      viruses tentatively assigned the neutralization epitope to the third constant
      domain, immediately C terminal to the V3 loop. These findings suggest the
      presence of at least one CD4-induced neutralization epitope on SIV, as is the
      case with human immunodeficiency virus type 1.

PMID- 10888658
TI  - Evidence for the packaging of multiple copies of Tf1 mRNA into particles and the
      trans priming of reverse transcription.
AB  - Long terminal repeat (LTR)-containing retrotransposons and retroviruses are close
      relatives that possess similar mechanisms of reverse transcription. The particles
      of retroviruses package two copies of viral mRNA that both function as templates
      for the reverse transcription of the element. We studied the LTR-retrotransposon
      Tf1 of Schizosaccharomyces pombe to test whether multiple copies of transposon
      mRNA participate in the production of cDNA. Using the unique self-priming
      property of Tf1, we obtained evidence that multiple copies of Tf1 mRNA were
      packaged into virus-like particles. By coexpressing two distinct versions of Tf1,
      we found that the bulk of reverse transcription that was initiated on one mRNA
      template was subsequently transferred to others. In addition, the first 11
      nucleotides of one mRNA were able to prime, in trans, the reverse transcription
      of another mRNA.

PMID- 10888659
TI  - Structural determinants of murine leukemia virus reverse transcriptase that
      affect the frequency of template switching.
AB  - Retroviral reverse transcriptases (RTs) frequently switch templates within the
      same RNA or between copackaged viral RNAs to generate mutations and
      recombination. To identify structural elements of murine leukemia virus RT
      important for template switching, we developed an in vivo assay in which RT
      template switching within direct repeats functionally reconstituted the green
      fluorescent protein gene. We quantified the effect of mutations in the YXDD
      motif, the deoxynucleoside triphosphate binding site, the thumb domain, and the
      RNase H domain of RT and hydroxyurea treatment on the frequencies of template
      switching. Hydroxyurea treatment and some mutations in RT increased the frequency
      of RT template switching up to fivefold, while all of the mutations tested in the
      RNase H domain decreased the frequency of template switching by twofold. Based on
      these results, we propose a dynamic copy choice model in which both the rate of
      DNA polymerization and the rate of RNA degradation influence the frequency of RT
      template switching.

PMID- 10888660
TI  - Two putative alpha-helical domains of human immunodeficiency virus type 1 Vpr
      mediate nuclear localization by at least two mechanisms.
AB  - To identify the domains of Vpr that are involved nuclear localization, we
      transfected HeLa cells with a panel of expression vectors that encode mutant Vpr
      protein with deletions or substitutions within putative domains.
      Immunofluorescence staining of transfected cells revealed that wild-type Vpr was
      localized predominantly in the nucleus and the nuclear envelope and certainly in
      the cytoplasm. Introduction of substitutions or deletions within alphaH1 or
      alphaH2 resulted, by contrast, in diffuse expression over the entire cell. In
      addition, double mutations within both of these alpha-helical domains led to the
      complete absence of Vpr from nuclei. Next, we prepared HeLa cells that express
      chimeric proteins which consist of the alphaH1 and alphaH2 domains fused
      individually with green fluorescent protein (GFP) and a Flag tag and extracted
      them with digitonin and Triton X-100 prior to fixation. Flag-alphaH1-GFP was
      detected in the nucleus but not in the cytoplasm, while Flag-alphaH2-GFP was
      retained predominantly in the nucleus and in a small amount in the cytoplasm. The
      immunostaining patterns were almost eliminated by substitutions in each chimeric
      protein. Thus, it appeared that the two alpha-helical domains might be involved
      in nuclear import by binding to certain cellular factors. Taken together, our
      data suggest that the two putative alpha-helical domains mediate the nuclear
      localization of Vpr by at least two mechanisms.

PMID- 10888661
TI  - Murine guanylate-binding protein: incomplete geranylgeranyl isoprenoid
      modification of an interferon-gamma-inducible guanosine triphosphate-binding
      protein.
AB  - Farnesylation of Ras proteins is necessary for transforming activity. Although
      farnesyl transferase inhibitors show promise as anticancer agents, prenylation of
      the most commonly mutated Ras isoform, K-Ras4B, is difficult to prevent because K
      Ras4B can be alternatively modified with geranylgeranyl (C20). Little is known of
      the mechanisms that produce incomplete or inappropriate prenylation. Among non
      Ras proteins with CaaX motifs, murine guanylate-binding protein (mGBP1) was
      conspicuous for its unusually low incorporation of [(3)H]mevalonate. Possible
      problems in cellular isoprenoid metabolism or prenyl transferase activity were
      investigated, but none that caused this defect was identified, implying that the
      poor labeling actually represented incomplete prenylation of mGBP1 itself.
      Mutagenesis indicated that the last 18 residues of mGBP1 severely limited C20
      incorporation but, surprisingly, were compatible with farnesyl modification.
      Features leading to the expression of mutant GBPs with partial isoprenoid
      modification were identified. The results demonstrate that it is possible to
      alter a protein's prenylation state in a living cell so that graded effects of
      isoprenoid on function can be studied. The C20-selective impairment in
      prenylation also identifies mGBP1 as an important model for the study of
      substrate/geranylgeranyl transferase I interactions.

PMID- 10888662
TI  - Accumulation of rab4GTP in the cytoplasm and association with the peptidyl-prolyl
      isomerase pin1 during mitosis.
AB  - Transport through the endocytic pathway is inhibited during mitosis. The
      mechanism responsible for this inhibition is not understood. Rab4 might be one of
      the proteins involved as it regulates transport through early endosomes, is
      phosphorylated by p34(cdc2) kinase, and is translocated from early endosomes to
      the cytoplasm during mitosis. We investigated the perturbation of the rab4 GTPase
      cycle during mitosis. Newly synthesized rab4 was less efficiently targeted to
      membranes during mitosis. By subcellular fractionation of mitotic cells, we found
      a large increase of cytosolic rab4 in the active GTP-form, an increase not
      associated with the cytosolic rabGDP chaperone GDI. Instead, phosphorylated rab4
      is in a complex with the peptidyl-prolyl isomerase Pin1 during mitosis, but not
      during interphase. Our results show that less efficient recruitment of rab4 to
      membranes and a bypass of the normal GDI-mediated retrieval of rab4GDP from early
      endosomes reduce the amount of rab4GTP on membranes during mitosis. We propose
      that phosphorylation of rab4 inhibits both the recruitment of rab4 effector
      proteins to early endosomes and the docking of rab4-containing transport
      vesicles. This mechanism might contribute to the inhibition of endocytic membrane
      transport during mitosis.

PMID- 10888663
TI  - Reversible block of the calcium release channel/ryanodine receptor by protamine,
      a heparin antidote.
AB  - Channel activity of the calcium release channel from skeletal muscle, ryanodine
      receptor type 1, was measured in the presence and absence of protamine sulfate on
      the cytoplasmic side of the channel. Single-channel activity was measured after
      incorporating channels into planar lipid bilayers. Optimally and suboptimally
      calcium-activated calcium release channels were inactivated by the application of
      protamine to the cytoplasmic side of the channel. Recovery of channel activity
      was not observed while protamine was present. The addition of protamine bound to
      agarose beads did not change channel activity, implying that the mechanism of
      action involves an interaction with the ryanodine receptor rather than changes in
      the bulk calcium concentration of the medium. The block of channel activity by
      protamine could be reversed either by removal by perfusion with buffer or by the
      addition of heparin to the cytoplasmic side of the channel. Microinjection of
      protamine into differentiated C(2)C(12) mouse muscle cells prevented caffeine
      induced intracellular calcium release. The results suggest that protamine acts on
      the ryanodine receptor in a similar but opposite manner from heparin and that
      protamine can be used as a potent, reversible inhibitor of ryanodine receptor
      activity.

PMID- 10888664
TI  - Exo1 roles for repair of DNA double-strand breaks and meiotic crossing over in
      Saccharomyces cerevisiae.
AB  - The MRE11, RAD50, and XRS2 genes of Saccharomyces cerevisiae are involved in the
      repair of DNA double-strand breaks (DSBs) produced by ionizing radiation and by
      radiomimetic chemicals such as methyl methanesulfonate (MMS). In these mutants,
      single-strand DNA degradation in a 5' to 3' direction from DSB ends is reduced.
      Multiple copies of the EXO1 gene, encoding a 5' to 3' double-strand DNA
      exonuclease, were found to suppress the high MMS sensitivity of these mutants.
      The exo1 single mutant shows weak MMS sensitivity. When an exo1 mutation is
      combined with an mre11 mutation, both repair of MMS-induced damage and processing
      of DSBs are more severely reduced than in either single mutant, suggesting that
      Exo1 and Mre11 function independently in DSB processing. During meiosis,
      transcription of the EXO1 gene is highly induced. In meiotic cells, the exo1
      mutation reduces the processing of DSBs and the frequency of crossing over, but
      not the frequency of gene conversion. These results suggest that Exo1 functions
      in the processing of DSB ends and in meiotic crossing over.

PMID- 10888665
TI  - Differential role of beta(1C) and beta(1A) integrin cytoplasmic variants in
      modulating focal adhesion kinase, protein kinase B/AKT, and Ras/Mitogen-activated
      protein kinase pathways.
AB  - The integrin cytoplasmic domain modulates cell proliferation, adhesion,
      migration, and intracellular signaling. The beta(1) integrin subunits, beta(1C)
      and beta(1A), that contain variant cytoplasmic domains differentially affect cell
      proliferation; beta(1C) inhibits proliferation, whereas beta(1A) promotes it. We
      investigated the ability of beta(1C) and beta(1A) to modulate integrin-mediated
      signaling events that affect cell proliferation and survival in Chinese hamster
      ovary stable cell lines expressing either human beta(1C) or human beta(1A). The
      different cytodomains of either beta(1C) or beta(1A) did not affect either
      association with the endogenous alpha(2), alpha(V), and alpha(5) subunits or cell
      adhesion to fibronectin or TS2/16, a mAb to human beta(1). Upon engagement of
      endogenous and exogenous integrins by fibronectin, cells expressing beta(1C)
      showed significantly inhibited extracellular signal-regulated kinase (ERK) 2
      activation compared with beta(1A) stable cell lines. In contrast, focal adhesion
      kinase phosphorylation and Protein Kinase B/AKT activity were not affected.
      Selective engagement of the exogenously expressed beta(1C) by TS2/16 led to
      stimulation of Protein Kinase B/AKT phosphorylation but not of ERK2 activation;
      in contrast, beta(1A) engagement induced activation of both proteins. We show
      that Ras activation was strongly reduced in beta(1C) stable cell lines in
      response to fibronectin adhesion and that expression of constitutively active
      Ras, Ras 61 (L), rescued beta(1C)-mediated down-regulation of ERK2 activation.
      Inhibition of cell proliferation in beta(1C) stable cell lines was attributable
      to an inhibitory effect of beta(1C) on the Ras/MAP kinase pathway because
      expression of activated MAPK kinase rescued beta(1C) antiproliferative effect.
      These findings show that the beta(1C) variant, by means of a unique signaling
      mechanism, selectively inhibits the MAP kinase pathway by preventing Ras
      activation without affecting either survival signals stimulated by integrins or
      cellular interactions with the extracellular matrix. These findings highlight a
      role for beta(1)-specific cytodomain sequences in maintaining an intracellular
      balance of proliferation and survival signals.

PMID- 10888666
TI  - AtVPS45 complex formation at the trans-Golgi network.
AB  - The Sec1p family of proteins are thought to be involved in the regulation of
      vesicle fusion reactions through interaction with t-SNAREs (target soluble N
      ethylmaleimide-sensitive factor attachment protein receptors) at the target
      membrane. AtVPS45 is a member of this family from Arabidopsis thaliana that we
      now demonstrate to be present on the trans-Golgi network (TGN), where it
      colocalizes with the vacuolar cargo receptor AtELP. Unlike yeast Vps45p, AtVPS45
      does not interact with, or colocalize with, the prevacuolar t-SNARE AtPEP12.
      Instead, AtVPS45 interacts with two t-SNAREs, AtTLG2a and AtTLG2b, that show
      similarity to the yeast t-SNARE Tlg2p. AtTLG2a and -b each colocalize with
      AtVPS45 at the TGN; however, AtTLG2a is in a different region of the TGN than
      AtTLG2b by immunogold electron microscopy. Therefore, we propose that complexes
      containing AtVPS45 and either AtTLG2a or -b define functional subdomains of the
      TGN and may be required for different trafficking events. Among other Arabidopsis
      SNAREs, AtVPS45 antibodies preferentially coprecipitate AtVTI1b over the closely
      related isoform AtVTI1a, implying that AtVTI1a and AtVTI1b also have distinct
      functions within the cell. These data point to a functional complexity within the
      plant secretory pathway, where proteins encoded by gene families have specialized
      functions, rather than functional redundancy.

PMID- 10888667
TI  - Inositol phosphorylceramide synthase is located in the Golgi apparatus of
      Saccharomyces cerevisiae.
AB  - The plasma membrane of eukaryotic cells differs in lipid composition from most of
      the internal organelles, presumably reflecting differences in many of its
      functions. In particular, the plasma membrane is rich in sphingolipids and
      sterols, one property of which is to decrease the permeability and increase the
      thickness of lipid bilayers. In this paper, we examine the length of
      transmembrane domains throughout the yeast secretory pathway. Although the
      transmembrane domains of cis and medial Golgi residents are similar to those of
      endoplasmic reticulum proteins, these domains lengthen substantially beyond the
      medial Golgi, suggesting a thickening of the bilayer. Yeast sphingolipids have
      particularly long acyl chains, and Aur1p, the inositol phosphorylceramide
      synthase that initiates yeast sphingolipid synthesis, was found to be located in
      the Golgi apparatus by both immunofluorescence and membrane fractionation, with
      its active site apparently in the Golgi lumen. Thus, it appears that sphingolipid
      synthesis in yeast takes place in the Golgi, separated from glycerophospholipid
      synthesis in the endoplasmic reticulum. A similar separation has been found in
      mammalian cells, and this conservation suggests that such an arrangement of
      enzymes within the secretory pathway could be important for the creation of
      bilayers of different thickness within the cell.

PMID- 10888668
TI  - Progesterone synthesized by Schwann cells during myelin formation regulates
      neuronal gene expression.
AB  - Previously, progesterone was found to regulate the initiation and biosynthetic
      rate of myelin synthesis in Schwann cell/neuronal cocultures. The mRNA for
      cytochrome P450scc (converts cholesterol to pregnenolone), 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD, converts pregnenolone to progesterone), and the
      progesterone receptor were found to be markedly induced during active myelin
      synthesis. However, the cells in the cocultures responsible for these changes
      were not identified. In this study, in situ hybridization was used to determine
      the localization of the enzymes responsible for steroid biosynthesis. The mRNA
      for cytochrome P450scc and 3beta-HSD were detected only in actively myelinating
      cocultures and were localized exclusively in the Schwann cells. Using
      immunocytochemistry, with minimal staining of the Schwann cells, we found the
      progesterone receptor in the dorsal root ganglia (DRG) neurons. The progesterone
      receptor in the neurons translocated into the nuclei of these cells when
      progesterone was added to neuronal cultures or during myelin synthesis in the
      cocultures. Additionally, a marked induction of the progesterone receptor was
      found in neuronal cultures after the addition of progesterone. The induction of
      various genes in the neurons was also investigated using mRNA differential
      display PCR in an attempt to elucidate the mechanism of steroid action on myelin
      synthesis. Two novel genes were induced in neuronal cultures by progesterone.
      These genes, along with the progesterone receptor, were also induced in
      cocultures during myelin synthesis, and their induction was blocked by RU-486 (a
      progesterone receptor antagonist). These genes were not induced in Schwann cells
      cultured alone after the addition of progesterone. These results suggest that
      progesterone is synthesized in Schwann cells and that it can indirectly regulate
      myelin formation by activating transcription via the classical steroid receptor
      in the DRG neurons.

PMID- 10888669
TI  - Insights into the structural organization of the I1 inner arm dynein from a
      domain analysis of the 1beta dynein heavy chain.
AB  - To identify domains in the dynein heavy chain (Dhc) required for the assembly of
      an inner arm dynein, we characterized a new motility mutant (ida2-6) obtained by
      insertional mutagenesis. ida2-6 axonemes lack the polypeptides associated with
      the I1 inner arm complex. Recovery of genomic DNA flanking the mutation indicates
      that the defects are caused by plasmid insertion into the Dhc10 transcription
      unit, which encodes the 1beta Dhc of the I1 complex. Transformation with Dhc10
      constructs encoding <20% of the Dhc can partially rescue the motility defects by
      reassembly of an I1 complex containing an N-terminal 1beta Dhc fragment and a
      full-length 1alpha Dhc. Electron microscopic analysis reveals the location of the
      missing 1beta Dhc motor domain within the axoneme structure. These observations,
      together with recent studies on the 1alpha Dhc, identify a Dhc domain required
      for complex assembly and further demonstrate that the intermediate and light
      chains are associated with the stem regions of the Dhcs in a distinct structural
      location. The positioning of these subunits within the I1 structure has
      significant implications for the pathways that target the assembly of the I1
      complex into the axoneme and modify the activity of the I1 dynein during
      flagellar motility.

PMID- 10888670
TI  - The APC11 RING-H2 finger mediates E2-dependent ubiquitination.
AB  - Polyubiquitination marks proteins for degradation by the 26S proteasome and is
      carried out by a cascade of enzymes that includes ubiquitin-activating enzymes
      (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). The
      anaphase-promoting complex or cyclosome (APC/C) comprises a multisubunit
      ubiquitin ligase that mediates mitotic progression. Here, we provide evidence
      that the Saccharomyces cerevisiae RING-H2 finger protein Apc11 defines the
      minimal ubiquitin ligase activity of the APC. We found that the integrity of the
      Apc11p RING-H2 finger was essential for budding yeast cell viability, Using
      purified, recombinant proteins we showed that Apc11p interacted directly with the
      Ubc4 ubiquitin conjugating enzyme (E2). Furthermore, purified Apc11p was capable
      of mediating E1- and E2-dependent ubiquitination of protein substrates, including
      Clb2p, in vitro. The ability of Apc11p to act as an E3 was dependent on the
      integrity of the RING-H2 finger, but did not require the presence of the cullin
      like APC subunit Apc2p. We suggest that Apc11p is responsible for recruiting E2s
      to the APC and for mediating the subsequent transfer of ubiquitin to APC
      substrates in vivo.

PMID- 10888671
TI  - Syntaxin 7 and VAMP-7 are soluble N-ethylmaleimide-sensitive factor attachment
      protein receptors required for late endosome-lysosome and homotypic lysosome
      fusion in alveolar macrophages.
AB  - Endocytosis in alveolar macrophages can be reversibly inhibited, permitting the
      isolation of endocytic vesicles at defined stages of maturation. Using an in
      vitro fusion assay, we determined that each isolated endosome population was
      capable of homotypic fusion. All vesicle populations were also capable of
      heterotypic fusion in a temporally specific manner; early endosomes, isolated 4
      min after internalization, could fuse with endosomes isolated 8 min after
      internalization but not with 12-min endosomes or lysosomes. Lysosomes fuse with
      12-min endosomes but not with earlier endosomes. Using homogenous populations of
      endosomes, we have identified Syntaxin 7 as a soluble N-ethylmaleimide-sensitive
      factor attachment protein receptor (SNARE) required for late endosome-lysosome
      and homotypic lysosome fusion in vitro. A bacterially expressed human Syntaxin 7
      lacking the transmembrane domain inhibited homotypic late endosome and lysosome
      fusion as well as heterotypic late endosome-lysosome fusion. Affinity-purified
      antibodies directed against Syntaxin 7 also inhibited lysosome fusion in vitro
      but had no affect on homotypic early endosome fusion. Previous work suggested
      that human VAMP-7 (vesicle-associated membrane protein-7) was a SNARE required
      for late endosome-lysosome fusion. A bacterially expressed human VAMP-7 lacking
      the transmembrane domain inhibited both late endosome-lysosome fusion and
      homotypic lysosome fusion in vitro. These studies indicate that: 1) fusion along
      the endocytic pathway is a highly regulated process, and 2) two SNARE molecules,
      Syntaxin 7 and human VAMP-7, are involved in fusion of vesicles in the late
      endocytic pathway in alveolar macrophages.

PMID- 10888673
TI  - Maintenance of human rearranged mitochondrial DNAs in long-term cultured
      transmitochondrial cell lines.
AB  - Large-scale rearrangements of mitochondrial DNA (mtDNA; i.e., partial
      duplications [dup-mtDNAs] and deletions [Delta-mtDNAs]) coexist in tissues in a
      subset of patients with sporadic mitochondrial disorders. In order to study the
      dynamic relationship among rearranged and wild-type mtDNA (wt-mtDNA) species, we
      created transmitochondrial cell lines harboring various proportions of wt-, Delta
      , and dup-mtDNAs from two patients. After prolonged culture in nonselective
      media, cells that contained initially 100% dup-mtDNAs became heteroplasmic,
      containing both wild-type and rearranged mtDNAs, likely generated via
      intramolecular recombination events. However, in cells that contained initially a
      mixture of both wt- and Delta-mtDNAs, we did not observe any dup-mtDNAs or other
      new forms of rearranged mtDNAs, perhaps because the two species were physically
      separated and were therefore unable to recombine. The ratio of wt-mtDNA to Delta
      mtDNAs remained stable in all cells examined, suggesting that there was no
      replicative advantage for the smaller deleted molecules. Finally, in cells
      containing a mixture of monomeric and dimeric forms of a specific Delta-mtDNA, we
      found that the mtDNA population shifted towards homoplasmic dimers, suggesting
      that there may be circumstances under which the cells favor molecules with
      multiple replication origins, independent of the size of the molecule.

PMID- 10888672
TI  - The Skn7 response regulator of Saccharomyces cerevisiae interacts with Hsf1 in
      vivo and is required for the induction of heat shock genes by oxidative stress.
AB  - The Skn7 response regulator has previously been shown to play a role in the
      induction of stress-responsive genes in yeast, e.g., in the induction of the
      thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor,
      Hsf1, is central to the induction of another set of stress-inducible genes,
      namely the heat shock genes. These two regulatory trans-activators, Hsf1 and
      Skn7, share certain structural homologies, particularly in their DNA-binding
      domains and the presence of adjacent regions of coiled-coil structure, which are
      known to mediate protein-protein interactions. Here, we provide evidence that
      Hsf1 and Skn7 interact in vitro and in vivo and we show that Skn7 can bind to the
      same regulatory sequences as Hsf1, namely heat shock elements. Furthermore, we
      demonstrate that a strain deleted for the SKN7 gene and containing a temperature
      sensitive mutation in Hsf1 is hypersensitive to oxidative stress. Our data
      suggest that Skn7 and Hsf1 cooperate to achieve maximal induction of heat shock
      genes in response specifically to oxidative stress. We further show that, like
      Hsf1, Skn7 can interact with itself and is localized to the nucleus under normal
      growth conditions as well as during oxidative stress.

PMID- 10888674
TI  - Reversible merger of membranes at the early stage of influenza hemagglutinin
      mediated fusion.
AB  - Fusion mediated by influenza hemagglutinin (HA), a prototype fusion protein, is
      commonly detected as lipid and content mixing between fusing cells. Decreasing
      the surface density of fusion-competent HA inhibited these advanced fusion
      phenotypes and allowed us to identify an early stage of fusion at physiological
      temperature. Although lipid flow between membranes was restricted, the contacting
      membrane monolayers were apparently transiently connected, as detected by the
      transformation of this fusion intermediate into complete fusion after treatments
      known to destabilize hemifusion diaphragms. These reversible connections
      disappeared within 10-20 min after application of low pH, indicating that after
      the energy released by HA refolding dissipated, the final low pH conformation of
      HA did not support membrane merger. Although the dynamic character and the lack
      of lipid mixing at 37 degrees C distinguish the newly identified fusion
      intermediate from the intermediate arrested at 4 degrees C described previously,
      both intermediates apparently belong to the same family of restricted hemifusion
      (RH) structures. Because the formation of transient RH structures at
      physiological temperatures was as fast as fusion pore opening and required less
      HA, we hypothesize that fusion starts with the formation of multiple RH sites,
      only a few of which then evolve to become expanding fusion pores.

PMID- 10888675
TI  - The Kar3p kinesin-related protein forms a novel heterodimeric structure with its
      associated protein Cik1p.
AB  - Proteins that physically associate with members of the kinesin superfamily are
      critical for the functional diversity observed for these microtubule motor
      proteins. However, quaternary structures of complexes between kinesins and
      kinesin-associated proteins are poorly defined. We have analyzed the nature of
      the interaction between the Kar3 motor protein, a minus-end-directed kinesin from
      yeast, and its associated protein Cik1. Extraction experiments demonstrate that
      Kar3p and Cik1p are tightly associated. Mapping of the interaction domains of the
      two proteins by two-hybrid analyses indicates that Kar3p and Cik1p associate in a
      highly specific manner along the lengths of their respective coiled-coil domains.
      Sucrose gradient velocity centrifugation and gel filtration experiments were used
      to determine the size of the Kar3-Cik1 complex from both mating pheromone-treated
      cells and vegetatively growing cells. These experiments predict a size for this
      complex that is consistent with that of a heterodimer containing one Kar3p
      subunit and one Cik1p subunit. Finally, immunoprecipitation of epitope-tagged and
      untagged proteins confirms that only one subunit of Kar3p and Cik1p are present
      in the Kar3-Cik1 complex. These findings demonstrate that the Kar3-Cik1 complex
      has a novel heterodimeric structure not observed previously for kinesin
      complexes.

PMID- 10888676
TI  - Regulation of membrane type-1 matrix metalloproteinase activation by proprotein
      convertases.
AB  - Membrane type-1 matrix metalloproteinase (MT1-MMP) is the prototypical member of
      a subgroup of membrane-anchored proteinases that belong to the matrix
      metalloproteinase family. Although synthesized as a zymogen, MT1-MMP plays an
      essential role in extracellular matrix remodeling after an undefined process that
      unmasks its catalytic domain. We now report the existence of a proprotein
      convertase-MT1-MMP axis that regulates the processing and functional activity of
      the metalloproteinase. Two sets of basic motifs in the propeptide region of MT1
      MMP are identified that potentially can be recognized by the proprotein
      convertase family of subtilisin-like proteases. Processing of proMT1-MMP as well
      as the expression of its proteolytic activity were blocked by mutating these
      recognition motifs or by inhibiting the proprotein convertases furin and PC6 with
      the serpin-based inhibitor alpha(1) antitrypsin Portland. Furthermore, both furin
      dependent and furin-independent MT1-MMP processing pathways are identified that
      require tethering of the metalloproteinase to the cell surface. These findings
      demonstrate the existence of a proprotein convertase-MT1-MMP axis that can
      regulate extracellular matrix remodeling.

PMID- 10888677
TI  - VAMP2, but not VAMP3/cellubrevin, mediates insulin-dependent incorporation of
      GLUT4 into the plasma membrane of L6 myoblasts.
AB  - Like neuronal synaptic vesicles, intracellular GLUT4-containing vesicles must
      dock and fuse with the plasma membrane, thereby facilitating insulin-regulated
      glucose uptake into muscle and fat cells. GLUT4 colocalizes in part with the
      vesicle SNAREs VAMP2 and VAMP3. In this study, we used a single-cell fluorescence
      based assay to compare the functional involvement of VAMP2 and VAMP3 in GLUT4
      translocation. Transient transfection of proteolytically active tetanus toxin
      light chain cleaved both VAMP2 and VAMP3 proteins in L6 myoblasts stably
      expressing exofacially myc-tagged GLUT4 protein and inhibited insulin-stimulated
      GLUT4 translocation. Tetanus toxin also caused accumulation of the remaining C
      terminal VAMP2 and VAMP3 portions in Golgi elements. This behavior was exclusive
      to these proteins, because the localization of intracellular myc-tagged GLUT4
      protein was not affected by the toxin. Upon cotransfection of tetanus toxin with
      individual vesicle SNARE constructs, only toxin-resistant VAMP2 rescued the
      inhibition of insulin-dependent GLUT4 translocation by tetanus toxin. Moreover,
      insulin caused a cortical actin filament reorganization in which GLUT4 and VAMP2,
      but not VAMP3, were clustered. We propose that VAMP2 is a resident protein of the
      insulin-sensitive GLUT4 compartment and that the integrity of this protein is
      required for GLUT4 vesicle incorporation into the cell surface in response to
      insulin.

PMID- 10888678
TI  - Transient nucleolar localization Of U6 small nuclear RNA in Xenopus Laevis
      oocytes.
AB  - Recent studies on the 2'-O-methylation and pseudouridylation of U6 small nuclear
      RNA (snRNA) hypothesize that these posttranscriptional modifications might occur
      in the nucleolus. In this report, we present direct evidence for the nucleolar
      localization of U6 snRNA and analyze the kinetics of U6 nucleolar localization
      after injection of in vitro transcribed fluorescein-labeled transcripts into
      Xenopus laevis oocytes. In contrast to U3 small nucleolar RNA (snoRNA) which
      developed strong nucleolar labeling over 4 h and maintained strong nucleolar
      signals through 24 h, U6 snRNA localized to nucleoli immediately after injection,
      but nucleolar staining decreased after 4 h. By 24 h after injection of U6 snRNA,
      only weak nucleolar signals were observed. Unlike the time-dependent profile of
      strong nucleolar localization of U6 snRNA or U3 snoRNA, injection of fluorescein
      labeled U2 snRNA gave weak nucleolar staining at all times throughout a 24-h
      period; U2 snRNA modifications are believed to occur outside of the nucleolus.
      The notion that the decrease of U6 signals over time was due to its trafficking
      out of nucleoli and not to transcript degradation was supported by the
      demonstration of U6 snRNA stability over time. Therefore, in contrast to snoRNAs
      like U3, U6 snRNA transiently passes through nucleoli.

PMID- 10888679
TI  - Luv1p/Rki1p/Tcs3p/Vps54p, a yeast protein that localizes to the late Golgi and
      early endosome, is required for normal vacuolar morphology.
AB  - We have characterized LUV1/RKI1/TCS3/VPS54, a novel yeast gene required to
      maintain normal vacuolar morphology. The luv1 mutant was identified in a genetic
      screen for mutants requiring the phosphatase calcineurin for vegetative growth.
      luv1 mutants lack a morphologically intact vacuole and instead accumulate small
      vesicles that are acidified and contain the vacuolar proteins alkaline
      phosphatase and carboxypeptidase Y and the vacuolar membrane H(+)-ATPase.
      Endocytosis appears qualitatively normal in luv1 mutants, but some portion (28%)
      of carboxypeptidase Y is secreted. luv1 mutants are sensitive to several ions
      (Zn(2+), Mn(2+), and Cd(2+)) and to pH extremes. These mutants are also sensitive
      to hygromycin B, caffeine, and FK506, a specific inhibitor of calcineurin. Some
      vacuolar protein-sorting mutants display similar drug and ion sensitivities,
      including sensitivity to FK506. Luv1p sediments at 100,000 x g and can be
      solubilized by salt or carbonate, indicating that it is a peripheral membrane
      protein. A Green Fluorescent Protein-Luv1 fusion protein colocalizes with the dye
      FM 4-64 at the endosome, and hemagglutinin-tagged Luv1p colocalizes with the
      trans-Golgi network/endosomal protease Kex2p. Computer analysis predicts a short
      coiled-coil domain in Luv1p. We propose that this protein maintains traffic
      through or the integrity of the early endosome and that this function is required
      for proper vacuolar morphology.

PMID- 10888680
TI  - Nucleus-vacuole junctions in Saccharomyces cerevisiae are formed through the
      direct interaction of Vac8p with Nvj1p.
AB  - Vac8p is a vacuolar membrane protein that is required for efficient vacuole
      inheritance and fusion, cytosol-to-vacuole targeting, and sporulation. By analogy
      to other armadillo domain proteins, including beta-catenin and importin alpha, we
      hypothesize that Vac8p docks various factors at the vacuole membrane. Two-hybrid
      and copurfication assays demonstrated that Vac8p does form complexes with
      multiple binding partners, including Apg13p, Vab2p, and Nvj1p. Here we describe
      the surprising role of Vac8p-Nvj1p complexes in the formation of nucleus-vacuole
      (NV) junctions. Nvj1p is an integral membrane protein of the nuclear envelope and
      interacts with Vac8p in the cytosol through its C-terminal 40-60 amino acids
      (aa). Nvj1p green fluorescent protein (GFP) concentrated in small patches or
      rafts at sites of close contact between the nucleus and one or more vacuoles.
      Previously, we showed that Vac8p-GFP concentrated in intervacuole rafts, where is
      it likely to facilitate vacuole-vacuole fusion, and in "orphan" rafts at the
      edges of vacuole clusters. Orphan rafts of Vac8p red-sifted GFP (YFP) colocalize
      at sites of NV junctions with Nvj1p blue-sifted GFP (CFP). GFP-tagged nuclear
      pore complexes (NPCs) were excluded from NV junctions. In vac8-Delta cells, Nvj1p
      GFP generally failed to concentrate into rafts and, instead, encircled the
      nucleus. NV junctions were absent in both nvj1-Delta and vac8-Delta cells.
      Overexpression of Nvj1p caused the profound proliferation of NV junctions. We
      conclude that Vac8p and Nvj1p are necessary components of a novel interorganelle
      junction apparatus.

PMID- 10888681
TI  - Two Drosophila innexins are expressed in overlapping domains and cooperate to
      form gap-junction channels.
AB  - Members of the innexin protein family are structural components of invertebrate
      gap junctions and are analogous to vertebrate connexins. Here we investigate two
      Drosophila innexin genes, Dm-inx2 and Dm-inx3 and show that they are expressed in
      overlapping domains throughout embryogenesis, most notably in epidermal cells
      bordering each segment. We also explore the gap-junction-forming capabilities of
      the encoded proteins. In paired Xenopus oocytes, the injection of Dm-inx2 mRNA
      results in the formation of voltage-sensitive channels in only approximately 40%
      of cell pairs. In contrast, Dm-Inx3 never forms channels. Crucially, when both
      mRNAs are coexpressed, functional channels are formed reliably, and the
      electrophysiological properties of these channels distinguish them from those
      formed by Dm-Inx2 alone. We relate these in vitro data to in vivo studies.
      Ectopic expression of Dm-inx2 in vivo has limited effects on the viability of
      Drosophila, and animals ectopically expressing Dm-inx3 are unaffected. However,
      ectopic expression of both transcripts together severely reduces viability,
      presumably because of the formation of inappropriate gap junctions. We conclude
      that Dm-Inx2 and Dm-Inx3, which are expressed in overlapping domains during
      embryogenesis, can form oligomeric gap-junction channels.

PMID- 10888682
TI  - Feedback interactions between cell-cell adherens junctions and cytoskeletal
      dynamics in newt lung epithelial cells.
AB  - To test how cell-cell contacts regulate microtubule (MT) and actin cytoskeletal
      dynamics, we examined dynamics in cells that were contacted on all sides with
      neighboring cells in an epithelial cell sheet that was undergoing migration as a
      wound-healing response. Dynamics were recorded using time-lapse digital
      fluorescence microscopy of microinjected, labeled tubulin and actin. In fully
      contacted cells, most MT plus ends were quiescent; exhibiting only brief
      excursions of growth and shortening and spending 87.4% of their time in pause.
      This contrasts MTs in the lamella of migrating cells at the noncontacted leading
      edge of the sheet in which MTs exhibit dynamic instability. In the contacted rear
      and side edges of these migrating cells, a majority of MTs were also quiescent,
      indicating that cell-cell contacts may locally regulate MT dynamics. Using
      photoactivation of fluorescence techniques to mark MTs, we found that MTs in
      fully contacted cells did not undergo retrograde flow toward the cell center,
      such as occurs at the leading edge of motile cells. Time-lapse fluorescent
      speckle microscopy of fluorescently labeled actin in fully contacted cells
      revealed that actin did not flow rearward as occurs in the leading edge lamella
      of migrating cells. To determine if MTs were required for the maintenance of cell
      cell contacts, cells were treated with nocodazole to inhibit MTs. After 1-2 h in
      either 10 microM or 100 nM nocodazole, breakage of cell-cell contacts occurred,
      indicating that MT growth is required for maintenance of cell-cell contacts.
      Analysis of fixed cells indicated that during nocodazole treatment, actin became
      reduced in adherens junctions, and junction proteins alpha- and beta-catenin were
      lost from adherens junctions as cell-cell contacts were broken. These results
      indicate that a MT plus end capping protein is regulated by cell-cell contact,
      and in turn, that MT growth regulates the maintenance of adherens junctions
      contacts in epithelia.

PMID- 10888685
TI  - Ambulatory pediatric association policy statement children and the environment

PMID- 10888683
TI  - Integrin alpha5/beta1 mediates fibronectin-dependent epithelial cell
      proliferation through epidermal growth factor receptor activation.
AB  - Human integrin alpha5 was transfected into the integrin alpha5/beta1-negative
      intestinal epithelial cell line Caco-2 to study EGF receptor (EGFR) and integrin
      alpha5/beta1 signaling interactions involved in epithelial cell proliferation. On
      uncoated or fibronectin-coated plastic, the integrin alpha5 and control (vector
      only) transfectants grew at similar rates. In the presence of the EGFR
      antagonistic mAb 225, the integrin alpha5 transfectants and controls were
      significantly growth inhibited on plastic. However, when cultured on fibronectin,
      the integrin alpha5 transfectants were not growth inhibited by mAb 225. The
      reversal of mAb 225-mediated growth inhibition on fibronectin for the integrin
      alpha5 transfectants correlated with activation of the EGFR, activation of MAPK,
      and expression of proliferating cell nuclear antigen. EGFR kinase activity was
      necessary for both MAPK activation and integrin alpha5/beta1-mediated cell
      proliferation. Although EGFR activation occurred when either the integrin alpha5
      transfected or control cells were cultured on fibronectin, coprecipitation of the
      EGFR with SHC could be demonstrated only in the integrin alpha5-transfected
      cells. These results suggest that integrin alpha5/beta1 mediates fibronectin
      induced epithelial cell proliferation through activation of the EGFR.

PMID- 10888686
TI  - From the presidents of the ambulatory pediatric association and the editor-in
      chief of ambulatory pediatrics

PMID- 10888687
TI  - Assessing immunization rates: the importance of denominators.

PMID- 10888684
TI  - Entry of the two infectious forms of vaccinia virus at the plasma membane is
      signaling-dependent for the IMV but not the EEV.
AB  - The simpler of the two infectious forms of vaccinia virus, the intracellular
      mature virus (IMV) is known to infect cells less efficiently than the
      extracellular enveloped virus (EEV), which is surrounded by an additional, TGN
      derived membrane. We show here that when the IMV binds HeLa cells, it activates a
      signaling cascade that is regulated by the GTPase rac1 and rhoA, ezrin, and both
      tyrosine and protein kinase C phosphorylation. These cascades are linked to the
      formation of actin and ezrin containing protrusions at the plasma membrane that
      seem to be essential for the entry of IMV cores. The identical cores of the EEV
      also appear to enter at the cell surface, but surprisingly, without the need for
      signaling and actin/membrane rearrangements. Thus, in addition to its known role
      in wrapping the IMV and the formation of intracellular actin comets, the membrane
      of the EEV seems to have evolved the capacity to enter cells silently, without a
      need for signaling.

PMID- 10888688
TI  - Effect of method of defining the active patient population on measured
      immunization rates in predominantly Medicaid and non-Medicaid practices.
AB  - OBJECTIVE: To examine the effect of patient selection criteria on immunization
      practice assessment outcomes. METHODS: In 3 high- (50%-85%) and 7 low- (<25%)
      Medicaid pediatric practices in urban eastern Virginia, we assessed immunization
      rates of children 12 and 24 months old comparing the standard criteria (charts in
      the active files excluding those that documented the child moved or went
      elsewhere) with 3 alternative criteria for selecting active patients: 1) follow
      up: the chart contained a complete immunization record or the patient was found
      to be active in the practice through follow-up contact by phone or mail; 2) seen
      in the past year: the chart indicated that the patient was seen in the practice
      in the past year; 3) consecutive: patients that were seen consecutively for any
      reason. RESULTS: Of the 1823 charts assessed in the high- and low-Medicaid
      practices, follow-up identified 61% and 83% as active patients; 78% and 95% were
      ever seen in the past year. At 24 months, mean practice immunization rates were
      lower for standard (70%) than all 3 alternative criteria (78%-86%). Immunization
      rate differences between standard and alternative criteria were greater in high-
      (17%-23%) than low-Medicaid practices (5%-13%). CONCLUSION: The standard for
      practice assessment should be based on a consistent definition of active patients
      as the immunization rate denominator.

PMID- 10888689
TI  - Cost-effectiveness of childhood immunization reminder/recall systems in urban
      private practices.
AB  - OBJECTIVE: To assess cost and cost-effectiveness of immunization reminder/recall
      systems in the private sector. METHODS: A manual postcard system (mail) was
      compared with a computer-based telephone system (autodialer) and control. Costs
      included time costs and the cost of equipment and supplies. The cost per child
      and the incremental cost of the intervention relative to control were computed.
      Cost-effectiveness ratios were computed for return visits and for immunizations
      delivered. RESULTS: The average cost per child was $2.28 for the mail group and
      $1.47 for the autodialer group. The incremental visit cost relative to the
      control was higher for the mail group ($9.52) than for the autodialer group
      ($3.48). The autodialer was more cost-effective in delivering immunizations: $4.
      06 per extra immunization (autodialer) versus $12.82 (mail). CONCLUSIONS:
      Excluding start-up costs, the autodialer system was most cost-effective.
      Including autodialer equipment costs, the autodialer system is more cost
      effective only for larger practices.

PMID- 10888690
TI  - A systematic review of treatments for infant colic.
AB  - OBJECTIVE: To conduct a systematic review of rigorously evaluated treatments for
      infant colic. METHODS: Online bibliographic databases were searched for the term
      "colic" in articles classified as clinical trials or randomized controlled trials
      and conducted in infants. Reference lists from review articles, meta-analyses,
      and the selected articles were also reviewed for potential studies. The abstracts
      or full-text articles of 57 relevant studies were examined, of which 22 met the
      selection criteria. The methodology and findings of all retrieved articles were
      critically evaluated. Data were extracted from each article regarding study
      methods, intervention studied, outcomes measured, and results. RESULTS: Four of
      the interventions studied had data of adequate quality and statistically
      significant numbers needed to treat (NNT): hypoallergenic diet (NNT = 6), soy
      formula (NNT = 2), reduced stimulation (NNT = 2), and herbal tea (NNT = 3).
      CONCLUSIONS: There are some effective therapies for infant colic, but additional
      rigorous studies of existing and alternative therapies are needed.

PMID- 10888691
TI  - Child development services in Medicaid managed care organizations: what does it
      take?
AB  - OBJECTIVE: We sought to understand why certain Medicaid managed care
      organizations (MMCOs) implemented child development services or programs and how
      they had done so. We also sought to identify barriers and facilitators to
      successful initiation and implementation of child development programs. METHODS:
      We conducted 9 key informant interviews and 4 site visits, and performed
      qualitative analyses to identify major themes across responses. RESULTS: We
      identified a small number of MMCOs with child development services. High-level
      support was crucial for program initiation; physician buy-in, staff support, and
      strong working relationships with outside health professionals or agencies were
      principal factors in successful program implementation. CONCLUSIONS: MMCOs that
      were committed to implementing child development services were successful in
      doing so, without external funding or regulatory mandate. The results provide
      valuable strategies for MMCOs interested in developing programs and for
      researchers and advocates interested in promoting child development services for
      low-income children.

PMID- 10888692
TI  - Exploring barriers to utilization of poison centers: a qualitative study of
      mothers attending an urban Women, Infants, and Children (WIC) Clinic.
AB  - OBJECTIVE: Prior research regarding poison center utilization identified risk
      factors for underutilization including race/ethnicity and acculturation. The
      purpose of this study was to understand factors contributing to underutilization
      of poison centers by low-income and minority mothers. METHODS: Focus groups were
      conducted with women attending an urban Women, Infants and Children clinic.
      Transcripts were analyzed for themes and key points. RESULTS: Twenty-two English
      speaking mothers and 21 Spanish-speaking mothers participated in 7 groups.
      Participants viewed poisoning as a serious problem to which all children are
      susceptible. English-speaking mothers had heard of the poison center but were
      unaware of services provided. They preferred to use the 911 system, which was
      viewed as immediate medical assistance and was an easy number to remember. Women
      questioned the credentials of the poison center staff. Spanish-speaking mothers
      had limited knowledge of poison centers and were concerned about language
      barriers. CONCLUSIONS: To increase utilization of poison centers, educational
      interventions must address these specific needs and misconceptions and should be
      produced in Spanish and English versions.

PMID- 10888693
TI  - Pediatric deaths attributable to complex chronic conditions: a population-based
      study of Washington State, 1980-1997.
AB  - OBJECTIVES: Advances in medical technology and public health are changing the
      causes and patterns of pediatric mortality. To better inform health care planning
      for dying children, we sought to determine if an increasing proportion of
      pediatric deaths were attributable to an underlying complex chronic condition
      (CCC), what the typical age of CCC-associated deaths was, and whether this age
      was increasing. DESIGN: Population-based retrospective cohort from 1980 to 1997,
      compiled from Washington State annual censuses and death certificates of children
      0 to 18 years old. MAIN OUTCOME MEASURES: For each of 9 categories of CCCs, the
      counts of death, mortality rates, and ages of death. RESULTS: Nearly one-quarter
      of the 21 617 child deaths during this period were attributable to a CCC. Death
      rates for the sudden infant death syndrome (SIDS), CCCs, and all other causes
      each declined, but less so for CCCs. Among infants who died because of causes
      other than injury or SIDS, 31% of the remaining deaths were attributable to a CCC
      in 1980 and 41% by 1997; for deaths in children 1 year of age and older, CCCs
      were cited in 53% in 1980, versus 58% in 1997. The median age of death for all
      CCCs was 4 months 9 days, with substantial differences among CCCs. No overall
      change in the age of death between 1980 to 1997 was found (nonparametric trend
      test). CONCLUSIONS: CCCs account for an increasing proportion of child deaths.
      The majority of these deaths occur during infancy, but the typical age varies by
      cause. These findings should help shape the design of support care services
      offered to children dying with chronic conditions and their families.

PMID- 10888694
TI  - An evaluation of an innovative multimedia educational software program for asthma
      management: report of a randomized, controlled trial.
AB  - BACKGROUND: Asthma continues to be a substantial cause of morbidity in pediatric
      populations. New strategies are needed to provide cost-effective educational
      interventions for children with asthma, particularly those in the inner city.
      OBJECTIVE: To assess the effectiveness of a multimedia educational software
      program about asthma. SETTING: A hospital-based primary care clinic and an
      affiliated neighborhood health center. DESIGN: Randomized, controlled trial.
      POPULATION: Children 3 to 12 years old with physician-diagnosed asthma.
      INTERVENTION: An interactive educational computer program, Asthma Control,
      designed to teach children about asthma and its management. Using a graphic
      display of a child going through simulated daily events, the game emphasizes: 1)
      monitoring; 2) allergen identification; 3) use of medications; 4) use of health
      services; and 5) maintenance of normal activity. Control group participants
      reviewed printed educational materials with a research assistant. OUTCOMES: Acute
      health care use (emergency department and outpatient) was the primary outcome.
      Secondary outcome measures included maternal report of asthma symptom severity,
      child functional status and school absences, satisfaction with care, and parental
      and child knowledge of asthma. RESULTS: A total of 137 families were enrolled in
      the study (76 intervention, 61 control). Both intervention and control groups
      showed substantial improvement in all outcomes during the 12-month follow-up
      period. Aside from improvement in knowledge after use of the computer program, no
      differences were demonstrated between the 2 groups in primary or secondary
      outcome measures. Children reported enjoyment of program use. CONCLUSIONS: This
      trial of an educational software program found that it did not produce greater
      improvement than occurred with review of traditional written materials. Because
      both groups showed substantial improvement over baseline, computer-based
      education may be more cost-effective. Alternatively, improvements in illness
      severity over time may overshadow the effects of such interventions. Rigorous
      comprehensive evaluations such as this are necessary to assess new interventions
      intended to improve management and outcomes of asthma.

PMID- 10888695
TI  - A national general pediatric clerkship curriculum: the process of development and
      implementation.
AB  - OBJECTIVE: To describe a new national general pediatrics clerkship curriculum,
      the development process that built national support for its use, and current
      progress in implementing the curriculum in pediatric clerkships at US allopathic
      medical schools. CURRICULUM DEVELOPMENT: A curriculum project team of pediatric
      clerkship directors and an advisory committee representing professional
      organizations invested in pediatric student education developed the format and
      content in collaboration with pediatric educators from the Council on Medical
      Student Education in Pediatrics (COMSEP) and the Ambulatory Pediatric Association
      (APA). An iterative process or review by clerkship directors, pediatric
      departmental chairs, and students finalized the content and built support for the
      final product. The national dissemination process resulted in consensus among
      pediatric educators that this curriculum should be used as the national
      curricular guideline for clerkships. MONITORING IMPLEMENTATION: Surveys were
      mailed to all pediatric clerkship directors before dissemination (November 1994),
      and in the first and third academic years after national dissemination (March
      1996 and September 1997). The 3 surveys assessed schools' implementation of
      specific components of the curriculum. The final survey also assessed ways the
      curriculum was used and barriers to implementation. OUTCOMES: The final
      curriculum provided objectives and competencies for attitudes, skills, and 18
      knowledge areas of general pediatrics. A total of 216 short clinical cases were
      also provided as an alternative learning method. An accompanying resource manual
      provided suggested strategies for implementation, teaching, and evaluation. A
      total of 103 schools responded to survey 1; 84 schools to survey 2; and 85
      schools responded to survey 3 from the 125 medical schools surveyed. Before
      dissemination, 16% of schools were already using the clinical cases. In the 1995
      1996 academic year, 70% of schools were using some or all of the curricular
      objectives/competencies, and 45% were using the clinical cases. Two years later,
      90% of schools surveyed were using the curricular objectives, 88% were using the
      competencies, 66% were using the clinical cases. The extent of curriculum use
      also increased. Schools using 11 or more of the 18 curriculum's knowledge areas
      increased from 50% (1995-1996) to 73% (1996-1997). CONCLUSION: This new national
      general pediatric clerkship curriculum developed broad support during its
      development and has been implemented very rapidly nationwide. During this period
      the COMSEP and the APA have strongly supported its implementation with a variety
      of activities. This development and implementation process can be a model for
      other national curricula.

PMID- 10888696
TI  - Let's go shopping: a tool for pediatric resident education.

PMID- 10888697
TI  - Reducing after-hours referrals by an after-hours call center with second-level
      physician triage.
AB  - OBJECTIVES: One-third of practices signing-out to The Children's Hospital Call
      Center in Denver, Colorado, choose to do second-level physician (SLP) triage for
      calls judged by the Center to require after-hours referral (AHR). We examined: 1)
      the effect of SLP triage on the rate of AHRs and 2) reasons for physicians'
      decisions. DESIGN: From January 1998 to August 1998 all calls from patients using
      a 5-member suburban pediatric practice judged by the Call Center to require AHR
      were referred to the practice's on-call physician who did SLP triage and
      completed a questionnaire. RESULTS: There were 955 eligible calls, 22% (N = 216)
      of which were initially given an urgent disposition by Call Center nurses.
      Physician questionnaires were completed for 97% (N = 209). Of patients initially
      triaged for AHR, 49% (N = 103) were subsequently given an AHR, 17% (N = 35) a
      next day office referral, and 34% (N = 71) home care and advice. Reasons for not
      urgently referring included the following: 1) medical problem didn't require
      urgent evaluation (95%, N = 99); 2) change in the patient's condition; (40% N =
      43); 3) prior knowledge of family's ability to evaluate and care for the patient
      (40%, N = 43); and 4) knowledge of the patient's medical history (18%, N = 19).
      After SLP triage the overall urgent referral rate was 11%. CONCLUSIONS: Signing
      out to a Call Center decreased physicians' after-hours calls by 77% and SLP
      triage halved the number of urgent after-hours referrals.

PMID- 10888698
TI  - A comparison of suburban and urban daytime telephone triage calls.
AB  - OBJECTIVE: To compare daytime nurse telephone triage calls received by a suburban
      practice with those received by a hospital-based, inner-city pediatric practice.
      METHODS: A research assistant, listening simultaneously with triage personnel,
      prospectively coded all calls received by the nurse triage telephone offices in 2
      pediatric practices. Calls were coded the first full, nonholiday week of 3
      consecutive summer and 3 consecutive winter months, alternating morning and
      afternoon sessions. One practice was suburban and had almost all commercially
      insured patients; the other was hospital-based, in an inner-city, and consisted
      mostly of patients with Medicaid coverage or no health insurance. RESULTS: A
      total of 901 calls were triaged in the suburban practice (SP) and 768 in the
      urban practice (UP). The chief complaints of calls regarding medical problems
      were similar at both sites. Difficulties with language were noted less often in
      SP compared with UP (1% vs 17%). The reason for the calls differed by site:
      medical problem relating to illness or injury (SP 55% vs UP 40%); social issue
      (SP 1% vs UP 9%); documentation request (SP 2% vs UP 7%); request for laboratory
      work (SP.3% vs UP 4%); and well child advice (SP 9% vs UP 5%). The disposition of
      calls also differed by site: telephone advice was offered significantly more in
      SP than in UP (32% vs 20%); fewer calls required the need for the medical record
      in SP than in UP (2% vs 12%). CONCLUSIONS: Calls received by a daytime nurse
      telephone triage office in an affluent SP and a UP are similar in regard to
      medical problems. Training programs can feasibly prepare physicians and nurses
      for both kinds of practice settings. The urban site received more calls affected
      by language and social issues. This could have administrative implications for
      staffing ratios, language skills of staff and knowledge of available support
      services.

PMID- 10888699
TI  - Improving adolescent rheumatology services in the UK.

PMID- 10888700
TI  - Impact of rheumatoid arthritis on physical function during the first five years.
      No longer a question mark?

PMID- 10888701
TI  - Antinuclear antibodies: cause of disease or caused by disease?

PMID- 10888702
TI  - Evidence-based treatment of systemic vasculitis.

PMID- 10888703
TI  - Audit of rheumatology services for adolescents and young adults in the UK.
      British Paediatric Rheumatology Group.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) is associated with significant
      morbidity in adulthood with at least one third of children continuing to have
      active inflammatory disease into their adult years and up to 60% of all patients
      continuing to have some limitation of their activities of daily living. A survey
      of service provision for these young people in the transition from paediatric to
      adult rheumatology care was therefore undertaken. METHODS: A postal questionnaire
      was sent to all 92 members of the British Paediatric Rheumatology Group,
      representing 61 units providing a paediatric rheumatology service in the UK and
      Eire. RESULTS: Fifty-five replies were received representing a 60% completion
      rate of doctors and 84% of units on the mailing list. The majority of respondents
      were adult rheumatologists (n = 36, 65%) with 42% of respondents based in
      teaching hospitals. A median of 24 patients (new and follow-up, range 1-225) were
      seen in a median of two paediatric rheumatology clinics (range 0-15) per month.
      Eighteen per cent of units had a dedicated adolescent clinic (n = 9) with a
      median of one clinic per month and a median number of new patients per month of
      two (range 0-24) and 10 review patients (4-32). All the adolescent clinics
      involved an adult rheumatologist with five having a paediatrician in clinic and
      four having access to a paediatrician. The majority of clinics involved a
      specialist registrar (n = 6), a nurse specialist (n = 6), an occupational
      therapist (n = 6) and a physiotherapist (n = 5). The majority of clinics had
      flexible entry and exit criteria. In seven clinics there was a standardized
      process of transfer, first discussed at a median age of 13 yr (range 12-16) but
      no unit provided literature or organized pre-visits for this process. A demand
      for patient information resources (e.g. disease and drug information, careers)
      specifically aimed at adolescents with rheumatic diseases was identified. Generic
      health issues were only addressed by two clinics. Obstacles to current service
      provision and ideas for future developments were identified. CONCLUSIONS: This
      survey identifies a heterogeneity of provision of healthcare for adolescents with
      rheumatic disease and highlights the potential for further research and
      development.

PMID- 10888704
TI  - How does functional disability in early rheumatoid arthritis (RA) affect patients
      and their lives? Results of 5 years of follow-up in 732 patients from the Early
      RA Study (ERAS)
AB  - OBJECTIVES: To assess the impact of rheumatoid arthritis (RA) on function and how
      this affects major aspects of patients' lives. METHODS: The inception cohort of
      RA patients was recruited from rheumatology out-patient departments in nine
      National Health Service (NHS) hospital trusts in England. All consecutive
      patients with RA of less than 2 yr duration, prior to any second-line (disease
      modifying) drug treatment were recruited and followed-up for 5 yr. Standard
      clinical, laboratory and radiological assessments, and all hospital-based
      interventions were recorded prospectively at presentation and yearly. The outcome
      measures were clinical remission and extra-articular features, functional ability
      [functional grades I-IV and Health Assessment Questionnaire (HAQ)], use of aids,
      appliances and home adaptations, orthopaedic interventions, and loss of paid
      work. RESULTS: A total of 732 patients completed 5 yr of follow-up, of whom 84%
      received second-line drugs. Sixty-nine (9.4%) had marked functional loss at
      presentation, compared with normal function in 243 (33%), and by 5 yr these
      numbers had increased in each group, respectively, to 113 (16%) and 296 (40%).
      Home adaptations and/or wheelchair use by 5 yr were seen in 74 (10%). Work
      disability was seen in 27% of those in paid employment at onset. One hundred and
      seventeen (17%) patients underwent orthopaedic surgery for RA, 55 (8%) for major
      joint replacements. Marked functional loss at 5 yr was more likely in women [odds
      ratio (OR) 1.63, 95% confidence interval (CI) 1.04-2.5], patients older than 60
      yr (OR 1.94, 95% CI 1.3-2.9), and with HAQ > 1.0 at presentation (OR 4.4, 95% CI
      2.8-7.0). CONCLUSIONS: Clinical profiles of RA patients treated with conventional
      drug therapy over 5 yr showed that a small proportion of patients (around 16%) do
      badly functionally and in terms of life events, whereas around 40% do relatively
      well. The details and exact figures of cumulative disability are likely to be
      useful to clinicians, health professionals and patients. The rate of progression
      and outcome in these patients can be compared against future therapies with any
      disease-modifying claims.

PMID- 10888705
TI  - End-stage coxarthrosis and gonarthrosis. Aetiology, clinical patterns and
      radiological features of idiopathic osteoarthritis.
AB  - OBJECTIVES: To determine and compare the aetiological background, clinical
      patterns and radiological features of idiopathic osteoarthritis (OA) of the hip
      and the knee warranting arthroplasty. METHODS: A total of 402 Caucasians
      consecutively undergoing total hip replacement (THR) or total knee replacement
      (TKR) for idiopathic OA at a major centre was surveyed. RESULTS: Previous joint
      injury was more common in the TKR group (P < 0.0001). However, both groups
      manifested a mixed occupational background, body mass indices similar to the
      general population and a predominance of females (F:M = 1.3-1.4:1). The TKR group
      had a significantly younger age of symptom onset (56 yr) than the THR group (61
      yr) but both groups had a tendency to bilateral arthroplasty (33%), nodal
      involvement (54-59%), a significant excess of right-sided replacements (1.8:1,
      THR; 2.2:1, TKR) and similar levels of pre-operative pain and disability. Up to
      40% of hips manifested acetabular dysplasia and 10% possible previous slipped
      upper femoral epiphyses. Eighty-five per cent with end-stage coxarthrosis or
      gonarthrosis had an identical pattern of radiographic disease contralaterally.
      CONCLUSIONS: Our data suggest the importance of a constitutional tendency to
      idiopathic, end-stage OA, a disorder traditionally associated with environmental
      factors leading to 'wear and tear'.

PMID- 10888706
TI  - Lupus patients with fatigue-is there a link with fibromyalgia syndrome?
AB  - OBJECTIVE: To determine whether fibromyalgia syndrome (FMS) was more common in
      patients with lupus who were complaining of fatigue. METHODS: We interviewed 216
      patients attending two lupus clinics, all of whom fulfilled the revised American
      College of Rheumatology (ACR) criteria for lupus. The patients completed a
      questionnaire and were examined to determine the presence of fatigue and whether
      they fulfilled the ACR criteria for FMS. Disease activity was measured using the
      British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus
      International Collaborating Clinics (SLICC)/ACR damage score. Measurements of
      erythrocyte sedimentation rate, complement C3, lymphocyte count and DNA titre
      were also performed. RESULTS: Fifty per cent of our patients complained of
      fatigue, but only 10% of these patients fulfilled criteria for FMS. FMS did not
      correlate with any measure of disease activity although patients with FMS had
      lower mean DNA antibody titres and mean SLICC/ACR damage scores. CONCLUSION: A
      minority of lupus patients with fatigue fulfil the ACR criteria for FMS. Other
      possible factors leading to fatigue should be considered.

PMID- 10888708
TI  - Serum KL-6 in adult patients with polymyositis and dermatomyositis.
AB  - OBJECTIVE: To determine the serum levels of KL-6, a mucin-like high-molecular
      weight glycoprotein, in polymyositis/dermatomyositis (PM/DM) patients. METHODS:
      Serum samples from 42 adult PM/DM patients and 38 healthy control subjects were
      examined using specific enzyme-linked immunosorbent assay (ELISA) systems.
      RESULTS: The serum levels of KL-6 in the PM/DM patients were significantly higher
      than those of the healthy controls. The elevated serum KL-6 levels correlated
      with the presence of interstitial lung disease (ILD) and decreased percentage
      diffusing capacity of carbon monoxide (%DLco) in the PM/DM patients. The serum KL
      6 levels inversely correlated with %DLco and percentage vital capacity.
      Additionally, the serum KL-6 levels were elevated in five of the seven DM
      patients with malignant neoplasia. CONCLUSIONS: These results suggest that the
      serum KL-6 level might be a useful serum marker for ILD and internal malignancy
      in PM/DM.

PMID- 10888707
TI  - The adrenal steroid status in relation to inflammatory cytokines (interleukin-6
      and tumour necrosis factor) in polymyalgia rheumatica.
AB  - OBJECTIVES: To determine the correlation between inflammatory cytokines and
      adrenal hormones in patients with polymyalgia rheumatica (PMR) and to compare the
      ratio of serum cortisol and androstenedione (ASD) or dehydroepiandrosterone
      sulphate (DHEAS) in normal subjects with PMR patients. METHODS: In 102 patients
      with PMR (32 beginning and 70 chronic disease) and 31 age-matched and sex-matched
      healthy subjects, ASD, cortisol, DHEAS, interleukin-6 (IL-6), and tumour necrosis
      factor (TNF) were measured by immunometric assays. RESULTS: Serum levels of IL-6
      were elevated in patients with PMR as compared with normal subjects (10.0 +/- 1.6
      vs 2.1 +/- 0.1 pg/ml, P = 0.01), which was not found for TNF. In PMR patients,
      serum levels of IL-6 were positively correlated with serum levels of ASD (P <
      0.001), cortisol (P < 0.001), and DHEAS (P = 0. 038) irrespective of
      corticosteroid treatment. Serum levels of cortisol in relation to IL-6 were
      significantly lower in patients with chronic disease and long-standing
      corticosteroid administration as compared with patients with recent onset of the
      disease and without corticosteroid therapy (P < 0.01). CONCLUSIONS: In PMR, as
      expected, there was an increase in IL-6 serum levels that was associated with
      elevated serum levels of ASD, DHEAS, and cortisol which was more marked in
      patients with recent-onset disease and without corticosteroids. However, serum
      levels of cortisol in patients with and without corticosteroids were lower than
      expected by considering the inflammatory status (increased IL-6). This may
      indicate a change in the hypothalamic-pituitary-adrenal (HPA) axis responsiveness
      to inflammatory stimuli such as IL-6 during chronic disease. Furthermore, there
      seems to be a shift of biosynthesis to cortisol in relation to DHEAS or ASD in
      chronic disease.

PMID- 10888709
TI  - Enhanced production of tissue inhibitor of metalloproteinases by peripheral blood
      mononuclear cells of rheumatoid arthritis patients responding to methotrexate
      treatment.
AB  - OBJECTIVE: To determine the effects of methotrexate (MTX) treatment of rheumatoid
      arthritis (RA) patients (a) on the circulating levels and (b) on the ex vivo
      production of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of
      metalloproteinases-1 (TIMP-1) by peripheral blood mononuclear cells (PBMNC).
      METHODS: Circulating levels, spontaneous ex vivo and in vitro production of MMP
      1, TIMP-1 and interleukin-6 (IL-6) were assessed by immunoassays in sera and
      culture supernatants of PBMNC derived from 27 patients with active RA before and
      3 months after beginning MTX treatment and from seven healthy subjects. The
      production and serum levels of MMP-1, TIMP-1 and IL-6 were correlated to the
      clinical response. RESULTS: PBMNC of RA patients showing >/= 20% improvement of
      the Paulus index after 3 months of MTX treatment (responders; n = 16) exhibited a
      significantly enhanced production of spontaneous TIMP-1 ex vivo which was
      associated with the enhanced synthesis of IL-6. In contrast, PBMNC of 11 patients
      with <20% improvement and/or progression of disease showed a marked reduction of
      TIMP-1 and IL-6 secretion. Circulating levels of TIMP-1 remained unchanged in
      both groups whereas serum IL-6 levels declined in the responder group. MMP-1 was
      detectable only in very few culture supernatants and RA sera. Moreover, PBMNC of
      healthy donors revealed that MTX also stimulated TIMP-1 and IL-6 release in
      vitro, IL-6 being partially responsible for the induction of TIMP-1 production.
      CONCLUSIONS: Both ex vivo and in vitro, the enhanced TIMP-1 production by PBMNC
      of RA patients and healthy individuals upon MTX treatment is associated with
      simultaneously enhanced IL-6 release, and enhanced ex vivo production of both is
      clearly associated with short-term clinical efficacy. This may reflect disease
      remission and favourable effects on host defence mechanisms against aberrant
      inflammation and extracellular matrix turnover in RA patients undergoing MTX
      treatment.

PMID- 10888710
TI  - The effect of lactation in the post-partum arthritis of MRL-lpr/fasmice.
AB  - OBJECTIVE: To investigate the effects of lactation on the post-partum arthritic
      flare in MRL-lpr/fas mice. METHODS: Three groups of mice were investigated. Group
      1: females whose litters were weaned at termination of the experiment; group 2:
      females whose litters were weaned at parturition; group 3: females who were not
      bred. Clinical evaluation was carried out at 5-day intervals following
      parturition. Blood samples were also collected during the course of the
      experiment and assayed for corticosterone and prolactin. Histological evaluation
      of the joints was assessed at day 30. RESULTS: The incidence of swelling and
      erythema, the bimalleolar ankle width and the histopathology were significantly
      reduced by removal of the litters at parturition. This correlated well with a
      decrease seen in prolactin levels in these females. Corticosterone, an
      immunomodulatory glucocorticoid, did not play a significant role in the arthritic
      flare. CONCLUSION: Our findings suggest that prolactin levels contribute to the
      inflammation seen in MRL-lpr/fas mice following parturition.

PMID- 10888711
TI  - Preliminary investigation of debridement of plantar callosities in rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine the effect of expert debridement of foot callosities on
      forefoot pain and plantar pressure distribution in rheumatoid arthritis (RA).
      METHODS: Plantar callosities on 14 feet of eight RA patients were debrided by a
      single podiatrist. Measurements of subjective pain severity in the forefoot and
      global arthritis pain were undertaken using a visual analogue scale, repeated at
      7-day intervals to the next treatment (28 days). Plantar pressures were recorded
      at the lesion sites using an in-shoe flexible transducer insole before and after
      lesion debridement. RESULTS: Following debridement, all patients reported
      symptomatic relief with an average change in pain score of 48% (P = 0.01) but the
      treatment effect was lost by 7 days. Immediately following scalpel debridement,
      peak pressures were elevated in 10 of 14 feet, whilst contact time was reduced
      and peak force increased. None, however, reached statistical significance.
      CONCLUSION: Scalpel debridement of forefoot plantar callosities reduces forefoot
      pain for about 7 days, but pressure distribution is not significantly altered.

PMID- 10888712
TI  - A comparison of the efficacy and safety of leflunomide and methotrexate for the
      treatment of rheumatoid arthritis.
AB  - OBJECTIVE: To compare the clinical efficacy and safety of leflunomide and
      methotrexate for the treatment of rheumatoid arthritis (RA). METHODS: In this
      multicentre, double-blind trial, 999 subjects with active RA were randomized to
      leflunomide (n = 501; loading dose 100 mg/day for 3 days, maintenance dose 20
      mg/day) or methotrexate (n = 498; 10-15 mg/week) for 52 weeks. After 1 yr the
      subjects could choose to stay for a second year of double-blind treatment. The
      primary end-points were tender and swollen joint counts and overall physician and
      patient assessments. Analyses were of the intent-to-treat group. RESULTS: After 1
      yr, the mean changes in the leflunomide and methotrexate groups, respectively,
      were -8.3 and -9.7 for tender joint count; -6.8 and -9.0 for swollen joint count;
      -0.9 and -1.2 for physician global assessment; -0.9 and -1.2 for patient global
      assessment; -14.4 and -28.2 for erythrocyte sedimentation rate. Improvements seen
      with methotrexate were significantly greater than those with leflunomide. No
      further improvement occurred after the second year of treatment and the
      distinction between the two treatments in terms of tender joint count and patient
      global assessment was lost. During the first year of treatment, a small and
      equivalent degree of radiographically assessed disease progression was seen with
      both drugs. After 2 yr, disease progression was significantly less with
      methotrexate. The most common treatment-related adverse events in both groups
      were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver
      enzyme levels. Over 2 yr, 21 subjects receiving methotrexate were withdrawn due
      to elevated plasma liver enzymes vs eight subjects taking leflunomide. Two drug
      related deaths from pulmonary causes were recorded with methotrexate vs no drug
      related deaths among the subjects receiving leflunomide. CONCLUSIONS: Both
      leflunomide and methotrexate are efficacious for prolonged treatment of RA. At
      the doses used, some clinical benefit of methotrexate over leflunomide was
      observed in the first year of treatment. This benefit must be weighed against the
      potential toxicity of this drug when used without folate supplementation.

PMID- 10888713
TI  - CD1 expression in psoriatic and rheumatoid arthritis.
AB  - OBJECTIVE: CD1 is a novel class of molecules which present non-protein antigens
      to T cells. The objective of this study was to evaluate the expression of CD1 in
      the skin and synovium of patients with psoriatic arthritis (PsA) in comparison
      with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Paired lesional
      skin (SK) and synovial membrane (SM) from four PsA patients, paired SK and SM
      from four RA patients, SM from eight RA and eight OA patients, and normal SK from
      four volunteers were studied using standard immunohistochemistry. RESULTS: In all
      PsA and RA skin samples CD1-positive cells were abundantly detected both in the
      dermis and in the epidermis. However, in the 24 SM examined CD1-positive cells
      were rarely found. In one patient only with RA, a few CD1a-positive cells were
      found in the SM. CD1b was scarcely expressed in the lining layer (LL) of five SM
      and in very few cells in the sublining layer (SL) of 11 SM. CD1c was rarely
      expressed in the LL of six SM and in very few cells in the SL of 13 SM.
      CONCLUSION: The paucity of CD1 in the PsA and RA synovium suggests that different
      subsets of antigen-presenting cells are involved in the pathogenesis of
      dermatitis and synovitis, respectively.

PMID- 10888714
TI  - The possible role of myocardial biopsy in systemic sclerosis.
AB  - The histopathological features of heart involvement in systemic sclerosis (SSc)
      are not widely known. In internal and transplantation medicine, myocardial
      biopsies are increasingly used to diagnose cardiomyopathies including
      myocarditis. In two SSc patients presenting with dyspnoea with no evidence of
      pulmonary involvement, the cause of the compromised heart function was sought by
      myocardial biopsy. Immunohistological analysis revealed an increased number of
      CD3+ + T cells indicating myocarditis in one, and increased amounts of
      fibroblasts in both SSc patients. The authors think that myocardial involvement
      in SSc should be differentially evaluated and they propose the use of myocardial
      biopsies as a tool to distinguish between inflammatory and fibrotic forms of
      heart involvement in SSc patients.

PMID- 10888715
TI  - Risk taking in patients with rheumatoid arthritis.

PMID- 10888716
TI  - Risk taking in patients with rheumatoid arthritis: are the risks of haemopoietic
      stem cell transplantation acceptable?

PMID- 10888717
TI  - Reply

PMID- 10888718
TI  - Systemic scleroderma associated with bilateral ulnar nerve entrapment at the
      elbow.

PMID- 10888719
TI  - Acute sarcoidosis: a difficult diagnosis.

PMID- 10888721
TI  - Robin goodfellow

PMID- 10888720
TI  - Oral methotrexate: hazard of different tablet strengths.

PMID- 10888722
TI  - Forthcoming events

PMID- 10888724
TI  - The CAG News Page.

PMID- 10888723
TI  - Announcements

PMID- 10888725
TI  - A causal role for Mycobacterium avium subspecies paratuberculosis in Crohn's
      disease?

PMID- 10888726
TI  - Practice guidelines for liver biopsy. Canadian Association of Gastroenterology.

PMID- 10888727
TI  - An analysis of an inflammatory bowel disease practice in an urban community
      hospital.
AB  - OBJECTIVES: To review an individual community gastroenterologist's experience
      with inflammatory bowel disease (IBD). The aspects studied were distribution of
      disease, need for hospital admission, immunosuppressants, systemic steroids, and
      surgery and its indications. The incidence of cancer was also reviewed. PATIENTS
      AND METHODS: The charts of all IBD patients (n=373) seen between 1993 and 1996 by
      an individual gastroenterologist in an urban community hospital were reviewed for
      the aforementioned information. Patients seen during this period may have been
      diagnosed with IBD before or during the period of 1993 to 1996. RESULTS: Of the
      373 patients, 219 had Crohn's disease (CD) and 154 had ulcerative colitis (UC).
      The most common age of onset for both groups was 20 to 29 years. Distal UC and
      distal Crohn's colitis patients rarely required surgery, hospitalization,
      systemic steroids or immunosuppressants. Eighty per cent of patients with small
      bowel CD and 51% of those with ileocolonic CD required at least one operation. Of
      the UC patients, 10.4% required surgery. Of the UC patients undergoing
      surveillance for cancer, none developed cancer but one developed significant
      dysplasia. CONCLUSIONS: In both CD and UC the site of the inflammation plays a
      major role in determining the need for hospitalization, surgery, systemic
      steroids and immunosuppressants. Distal UC, the most common form of UC in this
      group of patients, is a very benign disease. Of all forms of IBD, small bowel CD
      had the greatest need for hospitalization, surgery and systemic steroids.

PMID- 10888728
TI  - Results of screening first-degree relatives of patients with colorectal cancer: a
      community practice perspective.
AB  - Targeted screening by colonoscopy of asymptomatic first-degree relatives of
      patients with colorectal cancer (CRC) is promoted as a preventive health
      activity. This retrospective case control series details the results of this
      activity in a community-based referral gastroenterology practice. One advanced
      carcinoma and 22 adenomas in 15 patients were found in 118 individuals screened.
      Six per cent of those screened had advanced lesions (carcinoma, tubulovillous
      adenomas or adenomas larger than 1 cm). Colonoscopic screening of asymptomatic
      first-degree relatives of patients with CRC yields a limited number of clinically
      significant colonic neoplasms in this practice setting. Further cost-benefit data
      are needed.

PMID- 10888729
TI  - Effects of sodium fluoride on water and acid secretion, soluble mucus and
      adherent mucus of the rat stomach.
AB  - Chronic and acute ingestion of fluoride may lead to both structural and
      functional alterations of the gastric mucosa. The aim of this study was to
      investigate the effects of sodium fluoride on gastric secretion and mucosal
      barrier. Filling the rat stomach for 1 h with sodium fluoride (5 and 20 mmol/L)
      induced an increase in fluid, fucose and galactose output. This effect was
      accompanied by a marked pH-dependent reduction of titratable acidity of the
      lumen. The amount of Alcian blue bound to adherent mucus was reduced in a pH
      independent manner by sodium fluoride. The absence of a correlation between
      soluble glycoproteins and adherent mucus suggests that sodium fluoride does not
      stimulate mucus secretion, but rather acts as a barrier-breaking agent by its
      accumulation, together with acid, into the mucosa.

PMID- 10888730
TI  - Protective effect of vitamin E on gastric mucosal injury in rats with biliary
      obstruction.
AB  - Patients with liver disease display increased susceptibility to gastric mucosal
      damage. A role of free radicals has been suggested in the development of gastric
      mucosal damage in normal subjects. The effects of antioxidant vitamin E treatment
      on the liver and stomach in cirrhotic rats were examined. Fifty rats were divided
      into three groups. Cirrhosis was induced by bile duct ligation in 40 of 50 rats.
      Controls underwent a sham operation. Gastric mucosal lesions were produced by
      intragastric administration of 1 mL of 95% ethanol in all three groups. Twenty
      bile duct-ligated rats were injected intramuscularly with vitamin E (100
      mg/kg/day). Liver and stomach histology, and stomach malondialdehyde and
      glutathione levels were determined. Portal hypertension was measured. Macroscopic
      and microscopic gastric mucosal injury were significantly greater in the control
      and common bile duct-ligated groups than in the vitamin E-pretreated group
      (P<0.05). The tissue malondialdehyde and glutathione levels were significantly
      decreased in the vitamin E-administrated group compared with the common bile duct
      ligated group (P<0.001). Vitamin E administration may be cytoprotective for both
      the liver and gastric mucosa in bile duct-ligated rats.

PMID- 10888731
TI  - A critical approach to clinical practice guidelines.
AB  - The rate of publication of clinical practice guidelines for the management of
      common medical illnesses continues to accelerate. The appropriate dissemination
      and uptake of high quality practice guidelines can synthesize evidence, improve
      patient outcomes and enhance the efficiency of health care delivery. However, the
      methodological rigour and relevance of the growing number of publications
      labelled 'clinical practice guidelines' vary widely. Health care payers,
      providers and advocates must learn to appraise and interpret guideline
      recommendations critically. A simple and practical nine-question approach to
      evaluating the quality, relevance and effectiveness of clinical practice
      guidelines is presented.

PMID- 10888732
TI  - Consensus guidelines: agreement and debate surrounding the optimal management of
      Helicobacter pylori infection.
AB  - Helicobacter pylori is a recognized cause of a variety of gastroduodenal
      pathology. The high prevalence of both H pylori infection and related diseases
      within the community warrants its consideration as a public health care issue.
      The availability of reliable and safe noninvasive diagnostic techniques coupled
      with the development of effective and tolerable treatments has enabled primary
      health care personnel to manage this infection actively. The role of the primary
      care physician in the future management of H pylori infection is thus of central
      importance. The wealth of evidence produced by over 15 years of research into H
      pylori has expanded the list of disease associations and treatment benefits as
      well as elucidated the pathophysiological mechanisms involved. As a result, there
      has been a growing need to harmonize this information with clinical practice and
      to provide direction for the appropriate management by both specialists and
      general practitioners. Several national guidelines have been produced. The areas
      relating to H pylori infection that they considered and their recommendations
      vary. In 1994, the National Institutes of Health produced globally accepted
      recommendations for the management of H pylori-related peptic ulceration. The
      broader role of H pylori as a gastroduodenal pathogen and a public health care
      issue was not addressed. Recently, European and Canadian consensus guidelines
      have been published that identified overall management issues, including the role
      of primary and specialist care, and considered the appropriateness of employing
      eradication therapy for the spectrum of conditions in which H pylori has a direct
      or indirect association based on the available information. These guidelines,
      while in agreement regarding many issues, differ considerably in their
      recommendations for primary health care and regarding central issues such as the
      management of dyspepsia and gastric cancer. Some variations may reflect differing
      health care structures as well as the prevalence of both infection and associated
      diseases. However, the interpretation of evidence produced by recent research
      contributes to their conflicting statements.

PMID- 10888733
TI  - Causation of Crohn's disease by Mycobacterium avium subspecies paratuberculosis.
AB  - Mycobacterium avium subspecies paratuberculosis (MAP) is a member of the M avium
      complex (MAC). It differs genetically from other MAC in having 14 to 18 copies of
      IS900 and a single cassette of DNA involved in the biosynthesis of surface
      carbohydrate. Unlike other MAC, MAP is a specific cause of chronic inflammation
      of the intestine in many animal species, including primates. The disease ranges
      from pluribacillary to paucimicrobial, with chronic granulomatous inflammation
      like leprosy in humans. MAP infection can persist for years without causing
      clinical disease. The herd prevalence of MAP infection in Western Europe and
      North America is reported in the range 21% to 54%. These subclinically infected
      animals shed MAP in their milk and onto pastures. MAP is more robust than
      tuberculosis, and the risk that is conveyed to human populations in retail milk
      and in domestic water supplies is high. MAP is harboured in the ileocolonic
      mucosa of a proportion of normal people and can be detected in a high proportion
      of full thickness samples of inflamed Crohn's disease gut by improved culture
      systems and IS900 polymerase chain reaction if the correct methods are used. MAP
      in Crohn's disease is present in a protease-resistant nonbacillary form, can
      evade immune recognition and probably causes an immune dysregulation. As with
      other MAC, MAP is resistant to most standard antituberculous drugs. Treatment of
      Crohn's disease with combinations of drugs more active against MAC such as
      rifabutin and clarithromycin can bring about a profound improvement and, in a few
      cases, apparent disease eradication. New drugs as well as effective MAP vaccines
      for animals and humans are needed. The problems caused by MAP constitute a public
      health issue of tragic proportions for which a range of remedial measures are
      urgently needed.

PMID- 10888734
TI  - Appropriateness of liver biopsy.
AB  - This review aims to discuss the appropriateness of liver biopsy in two frequent
      liver diseases, hepatitis C and alcoholic liver disease. The medical literature,
      published between 1965 and 1999, was reviewed by using MEDLINE. Only 0.1% of the
      publications were devoted specifically to the appropriateness of liver biopsy.
      Not all studies observed a significant agreement among doctors on the decision to
      use liver biopsy. Therefore, there is a possibility that hepatologists have
      significant, heterogeneous opinions concerning the appropriateness of liver
      biopsy. Appropriateness should be evaluated for different techniques such as
      percutaneous liver biopsy, guided or not by ultrasonography, and the types of
      needles, automatic or not. The present paper reviews the evaluation of liver
      biopsy appropriateness in the real world, the adverse events and mortality of
      liver biopsy, and the appropriateness of liver biopsy in alcoholic liver disease
      and chronic hepatitis C. The authors conclude that liver biopsy is used
      extensively, but its appropriateness has not been evaluated perfectly. Therefore,
      further evaluation of the appropriateness of liver biopsy in the practical
      algorithm of such diseases is needed.

PMID- 10888735
TI  - Immunocytochemical analysis of the mouse retina.
AB  - Transgenic mice provide a new approach for studying the structure and function of
      the mammalian retina. In the past, the cellular organization of the mammalian
      retina was investigated preferentially in primates, cats, and rats but rarely in
      mice. In the current study, the authors applied 42 different immunocytochemical
      markers to sections of the mouse retina and studied their cellular and synaptic
      localization by using confocal microscopy. The markers applied were from three
      major groups: 1) antibodies against calcium-binding proteins, such as calbindin,
      parvalbumin, recoverin, or caldendrin; 2) antibodies that recognize specific
      transmitter systems, such as glycine, gamma-aminobutyric acid, or acetylcholine;
      and 3) antibodies that recognize transmitter receptors and show their aggregation
      at specific synapses. Only a few markers labeled only one cell type: Most
      antibodies recognized specific groups of neurons. These were analyzed in more
      detail in double-labeling experiments with different combinations of the
      antibodies. In light of their results, the authors offer a list of
      immunocytochemical markers that can be used to detect possible changes in the
      retinal organization of mutant mice.

PMID- 10888736
TI  - Morphologic features and electrical membrane properties of projection neurons in
      the marginal layer of the medullary dorsal horn of the rat.
AB  - Possible correspondence between morphologic features and electrical membrane
      properties of projection neurons in lamina I [the marginal zone (MZ)] of the
      caudal subnucleus of the spinal trigeminal nucleus [the medullary dorsal horn
      (MDH)] was examined by using intracellular recordings and biocytin-injections
      combined with histochemical and immunohistochemical staining techniques. The
      experiments were done in horizontal slice preparations of the rat brain. Thirteen
      MZ neurons were recorded stably and stained successfully. These neurons were
      confirmed to send their axons to the brain regions outside the MDH by camera
      lucida reconstruction. They were divided into two types on the basis of branching
      patterns of their axons within the MDH: Type I projection (P-I) neurons (n = 7
      neurons) had main axons that rarely emitted axon collaterals within the MDH,
      whereas type II projection (P-II) neurons (n = 6 neurons) had main axons that
      emitted many axon collaterals within laminae I, II (substantia gelatinosa), and
      III (magnocellular part) of the MDH and also to the spinal tract of the
      trigeminal nerve; these axon collaterals usually constituted a dense mesh of
      axonal processes within laminae I and II of the MDH, especially in lamina II.
      About half of the neurons of each type showed immunoreactivity for the neurokinin
      1 receptor. Resting membrane potentials were significantly more positive in P-I
      neurons than in P-II neurons. The P-II neurons had higher input resistance, a
      longer membrane time constant, and a higher threshold for spike than P-I neurons.
      In response to weak, long depolarizing current pulses, P-II neurons often showed
      slow ramp depolarization; the same neurons exhibited delayed repolarization to
      the resting potential (slow after depolarization) after the offset of the long
      depolarizing current pulses. Neither the slow-ramp depolarization nor the slow
      after depolarization was observed in P-I neurons. Slow return to resting membrane
      potential after offset of hyperpolarizing current pulses also was observed
      frequently in P-II neurons but not in P-I neurons. The results indicate that P-II
      neurons differ in their membrane properties compared with P-I neurons, and P-II
      neurons may be involved in the local circuit mechanism within the MDH more deeply
      than P-I neurons.

PMID- 10888737
TI  - Morphological and physiological comparisons of two types of allatostatin in the
      brain and retrocerebral complex of the tomato moth, Lacanobia oleracea
      (Lepidoptera: Noctuidae).
AB  - The cellular localisation of two types of allatostatin in the brain and
      retrocerebral complex has been studied in larvae of Lacanobia oleracea
      (Noctuidae) using antisera against Manduca sexta allatostatin (Mas-AS) and two
      members of the Y/FXFGL-NH(2) allatostatin family. The axons of two groups of Mas
      AS-immunoreactive neurosecretory cells in the pars lateralis form part of the
      nervi corporis cardiaci (NCC 1). They exit the brain as the combined NCC 1 and
      NCC 2 and pass through the corpora cardiaca (CC), where they divide to innervate
      the corpora allata (CA) and the mandibular (salivary) gland. The presence of Mas
      AS immunoreactivity in the CA is consistent with the inhibitory action of this
      peptide on juvenile hormone (JH) biosynthesis in L. oleracea. Immunoreactivity in
      the mandibular gland nerve suggests an additional, as yet unidentified role for
      this peptide. Cells of the pars intermedialis, the main contributors to NCC 2, do
      not show Mas-AS immunoreactivity. The distribution of Y/FXFGL-NH(2)
      immunoreactivity is different from that of Mas-AS. Although there are fewer cells
      in the pars lateralis, immunoreactivity is observed in certain neurones of the
      pars intermedialis and the tritocerebrum. Axons of these latter neurones
      contribute to NCC 2 and NCC 3, respectively, and, combined with those from NCC 1,
      result in the prominent occurrence of Y/FXFGL-NH(2) immunoreactivity in the CC,
      particularly in the storage lobe. The CA has far less Y/FXFGL-NH(2)
      immunoreactivity compared with Mas-AS. In bioassays, the Y/FXFGL-NH(2)
      allatostatins did not inhibit JH synthesis by CA of L. oleracea.

PMID- 10888738
TI  - Glial-defined rhombomere boundaries in developing Xenopus hindbrain.
AB  - The vertebrate central nervous system is characterized by regional
      specialization, which arises during early development and contributes to
      patterning the emerging central nervous system (CNS). In the hindbrain,
      rhombomeres demarcate nonoverlapping regions of the CNS that give rise to
      distinct neural structures. The cellular structures that define boundaries
      between adjacent rhombomeres are as yet unclear. However, in certain species the
      boundary regions between discrete CNS regions appear to be defined by specialized
      glial cells. Here, we show that in developing Xenopus, DM gamma, a membrane
      protein of the proteolipid protein family, is expressed in a subset of radial
      glia. During development, DM gamma transcripts are first expressed in presumptive
      glial cells throughout the hindbrain, but later become confined to the
      ventricular zone at rhombomere centers, whereas the protein is exclusively
      expressed in radial glial cell processes that occupy the rhombomere boundary
      regions. Likewise, early in development vimentin and glial fibrillary acidic
      protein are extensively coexpressed in hindbrain radial glia but subsequently
      define distinct rhombomere domains: vimentin remains localized in radial glia at
      the rhombomere boundary regions, whereas expression of glial fibrillary acidic
      protein becomes restricted to the centers. Moreover, radial glial processes at
      the boundary region are distinguishable from those at the center region; the
      processes of the boundary region radial glia extend upward in a fan-shaped
      arrangement and are encircled by the processes from the center glia. These data
      suggest that an early event in determining rhombomere topology is the
      specification of both morphologically and biochemically distinct subsets of
      radial glia.

PMID- 10888739
TI  - Thermotaxis and thermosensory neurons in infective larvae of Haemonchus
      contortus, a passively ingested nematode parasite.
AB  - As a basis for studies of thermal behavior of infective larvae (L3) of Haemonchus
      contortus resulting from ablation of amphidial neurons, the locations of the
      amphidial cell bodies in the hatchling larva (L1) were compared with their
      locations in the L3. We sought to verify that killing each targeted cell body in
      L1 destroys the putative corresponding dendrite of the L3. These comparisons
      confirmed the predicted cell body-to-dendrite connections, as well as
      similarities in the general amphidial structure of the two stages. We then
      conducted a series of studies using laser microbeam ablation of amphidial cell
      bodies in the L1 to determine the role of specific neurons in the thermal
      behavior of the L3. In a thermal gradient, normal L3 of H. contortus migrate to
      the temperature at which they were cultured and/or maintained. Larvae grown at 16
      degrees or 26 degrees C migrate appropriately to either of these temperatures.
      Larvae grown to the L3 stage at 16 degrees C and then moved to 26 degrees C
      become acclimated to this temperature and thereafter migrate to it. However, when
      the putative thermosensory neurons, the finger cell neurons (AFD), were ablated
      in hatchling larvae with a laser microbeam, and these were grown to the L3 stage
      and tested on a radial thermal gradient, they failed to migrate to their culture
      temperature. Instead, they moved actively and continuously over much of the assay
      plate surface, with no obviously oriented cryo- or thermotactic movement.
      Ablation-control larvae, those in which putatively chemosensory neuron classes
      ASE or AWC were killed, migrated normally to their culture temperature. When the
      RIA interneurons (identified by positional homology with those of Caenorhabditis
      elegans) were ablated, the operated larvae moved actively, but circled near the
      initial placement point; control larvae, in which other nonamphidial neurons were
      killed, migrated normally. These results indicate that the finger cell neurons
      (AFD) are the primary thermosensory class in H. contortus. The RIA-class neurons
      integrate thermal responses in H. contortus, as do their putative structural
      homologs in C. elegans, but the behavior of H. contortus subsequent to RIA
      ablation is strikingly different.

PMID- 10888740
TI  - Expression of the IgLON cell adhesion molecules Kilon and OBCAM in hypothalamic
      magnocellular neurons.
AB  - The vasopressin (AVP) and oxytocin (OXT) magnocellular neurons in the
      hypothalamic supraoptic (SON) and paraventricular nuclei (PVN) display reversible
      structural plasticity of neurons and glial cells under different conditions of
      neuropeptide secretion. In the present study, we investigated the expression of
      two immunoglobulin superfamily (IgSF) proteins, Kilon and OBCAM, in the
      magnocellular neurons by using monoclonal antibodies. Anti-Kilon antibody reacted
      specifically with the bacterially expressed recombinant Kilon but not with the
      recombinant OBCAM, and similarly anti-OBCAM antibody specifically recognized the
      recombinant OBCAM. Western blotting analysis revealed the specific expression of
      Kilon and OBCAM in the SON homogenates. Although Kilon and OBCAM of the SON
      homogenates were present as the insoluble form, most Kilon was present in the
      Triton-insoluble fraction, and OBCAM was localized mainly in the Triton-soluble
      fraction. Immunocytochemistry revealed Kilon and OBCAM immunoreactivity in the
      magnocellular neurons of the SON and PVN of the rat hypothalamus compared with
      outside of the SON and PVN in the hypothalamus. The double-labeling study with
      confocal microscopy further demonstrated that Kilon immunoreactivity was observed
      mainly in the dendrites of AVP-secreting neurons and also occasionally OXT
      secreting neurons. However, OBCAM immunoreactivity was exclusively seen in the
      dendrites of AVP-secreting magnocellular neurons. Chronic physiological
      stimulation by 2% NaCl had no effect on the expression levels of either IgLON
      protein in the SON. Our study thus demonstrated specific expression of Kilon and
      OBCAM in the hypothalamic magnocellular neurons, particularly in dendrites,
      suggesting that they confer on magnocellular neurons the ability to rearrange
      dendritic connectivity.

PMID- 10888741
TI  - The role of Clock in the developmental expression of neuropeptides in the
      suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus (SCN) is the dominant circadian pacemaker in mammals.
      To understand better the ontogeny of mouse SCN and the role of the pacemaker in
      peptide expression, the authors examined the distribution of cells that were
      immunoreactive for vasopressin (AVP) or vasoactive intestinal polypeptide (VIP)
      in wild type and Clock mutant mice at two developmental stages. Clock homozygous
      mice failed to show the dramatic increase in the number of VIP-immunoreactive
      (VIP-ir) neurons from postnatal day 6 (P6) to P30 that was found in the SCN of
      wild type mice. The number of AVP-ir neurons was relatively constant in the
      postnatal SCN but was significantly reduced in Clock/Clock mice. The effects of
      the Clock mutation varied with position in the SCN for both peptides.
      Densitometry of immunolabeled brains indicated that the Clock mutation reduced
      AVP expression specifically in the SCN and not in other brain areas. The SCN did
      not significantly change shape or size with age or Clock genotype. Taken
      together, these results indicate that the neonatal mouse SCN has its full
      complement of cells, some of which are not yet mature in their neuropeptide
      content. Furthermore, the observation that the Clock mutation appears to act on a
      subset of AVP and VIP cells suggests heterogeneity within these cell classes in
      the SCN.

PMID- 10888742
TI  - Levels of nerve growth factor and neurotrophin-3 are affected differentially by
      the presence of p75 in sympathetic neurons in vivo.
AB  - The development and survival of sympathetic neurons is critically dependent on
      the related neurotrophic factors nerve growth factor (NGF) and neurotrophin-3
      (NT3), the actions of which must be executed appropriately despite spatial and
      temporal overlaps in their activities. The tyrosine receptor kinases, trkA and
      trkC, are the cognate receptors for NGF and NT3, respectively. The p75
      neurotrophin receptor has been implicated in neurotrophin binding and signaling
      for both NGF and NT3. In this study, the authors used mice that overexpressed NGF
      (NGF-OE) or NT3 (NT3-OE) in skin and mice that lacked p75 (p75(-/-)) to
      understand the dynamics of sympathetic neuron response to each neurotrophin and
      to address the role of p75. NGF and NT3 were measured in sympathetic ganglia and
      skin (a major target of sympathetic neurons) by using the enzyme-linked
      immunosorbent assay (ELISA) technique. A three- to four-fold increase in skin NT3
      was seen in both NT3-OE and p75(-/-) mice. Moreover, both mouse lines exhibited a
      three-fold increase in ganglionic NT3. However, the increase in ganglionic NT3
      was accompanied by a decrease in ganglionic NGF in p75(-/-) mice but not in NT3
      OE mice. This indicated that p75 plays an important role in determining the level
      of NGF within sympathetic neurons. In NGF-OE mice, the overexpression of NGF was
      correlated with increased ganglionic NGF and increased ganglionic expression of
      p75 mRNA. In addition, in NGF-OE mice, ganglionic trkC expression was decreased,
      as was the amount of NT3 present within sympathetic ganglia. These results
      indicate that the level of p75 is integral in determining the level of
      sympathetic NGF and that NGF competes with NT3 by increasing the expression of
      p75 and decreasing the expression of trkC.

PMID- 10888743
TI  - Periaqueductal gray matter projections to midline and intralaminar thalamic
      nuclei of the rat.
AB  - The periaqueductal gray matter (PAG) projections to the intralaminar and midline
      thalamic nuclei were examined in rats. Phaseolus vulgaris-leucoagglutinin (PHA-L)
      was injected in discrete regions of the PAG, and axonal labeling was examined in
      the thalamus. PHA-L was also placed into the dorsal raphe nuclei or nucleus of
      Darkschewitsch and interstitial nucleus of Cajal as controls. In a separate group
      of rats, the retrograde tracer cholera toxin beta-subunit (CTb) was injected into
      one of the intralaminar thalamic nuclei-lateral parafascicular, medial
      parafascicular, central lateral (CL), paracentral (PC), or central medial nucleus
      or one of the midline thalamic nuclei-paraventricular (PVT), intermediodorsal
      (IMD), mediodorsal, paratenial, rhomboid (Rh), reuniens (Re), or caudal ventral
      medial (VMc) nucleus. The distribution of CTb labeled neurons in the PAG was then
      mapped. All PAG regions (the four columns of the caudal two-thirds of the PAG
      plus rostral PAG) and the precommissural nucleus projected to the rostral PVT,
      IMD, and CL. The ventrolateral, lateral, and rostral PAG provided additional
      inputs to most of the other intralaminar and midline thalamic nuclei. PAG inputs
      to the VMc originated from the rostral and ventrolateral PAG areas. In addition,
      the lateral and rostral PAG projected to the zona incerta. No evidence was found
      for a PAG input to the ventroposterior lateral parvicellular, ventroposterior
      medial parvicellular, caudal PC, oval paracentral, and reticular thalamic nuclei.
      PAG --> thalamic circuits may modulate autonomic-, nociceptive-, and behavior
      related forebrain circuits associated with defense and emotional responses.

PMID- 10888744
TI  - Axonal branching pattern of neurons of the subthalamic nucleus in primates.
AB  - Axonal projections arising from the subthalamic nucleus (STN) in cynomolgus
      monkeys (Macaca fascicularis) were traced after labeling small pools (5-15 cells)
      of neurons with biotinylated dextran amine. Seventy-five single axons were
      reconstructed from serial sagittal sections with a camera lucida. Most of the STN
      labeled cells displayed five to eight long, sparsely spined dendrites that
      arborized mostly along the main axis of the nucleus. Based on their axonal
      targets, five distinct types of STN projection neurons have been identified: 1)
      neurons projecting to the substantia nigra pars reticulata (SNr), the internal
      (GPi) and external (GPe) segments of the globus pallidus (21.3%); 2) neurons
      targeting SNr and GPe (2. 7%); 3) neurons projecting to GPi and GPe (48%); 4)
      neurons targeting GPe only (10.7 %); and 5) neurons with axons that coursed
      toward the sriatum, but whose terminal arborization could not be visualized in
      detail (17.3%). Axons of the first two types bifurcated into rostral
      subthalamopallidal and caudal pallidonigral branches. However, the majority of
      STN axons had only a single branch that coursed rostrally toward the pallidum and
      striatum. These results reveal that, in contrast to current beliefs, the primate
      STN is not a monolithic entity. This nucleus harbors several subtypes of
      projection neurons, each endowed with a highly patterned set of collaterals. This
      organization allows STN neurons to exert a multifarious effect not only on the
      GPe, with which the STN is reciprocally connected, but also on the two major
      output structures of the basal ganglia, the SNr and the GPi.

PMID- 10888745
TI  - Distribution of the integrin beta 1 subunit on radial cells in the embryonic and
      adult avian retina.
AB  - The distribution of the beta1 integrin subunit was investigated in the developing
      and adult chick retina at the light and electron microscopic levels, using two
      different monoclonal antibodies. Western blotting revealed a single band with a
      molecular weight of approximately 130 kDa in the retina and in a number of other
      tissues, indicating the specificity of the antibodies. In the retina,
      immunoreactivity was detected on radial cells spanning the entire width between
      the pigment epithelium and the vitreal border. These cells were undifferentiated
      neuroepithelial cells at early stages and radial Muller glial cells at later
      stages of development. At all stages, the beta1 subunit was concentrated at the
      vitreal border of the retina around the inner limiting membrane. Mechanical
      isolation of the inner limiting membrane, as well as immunoelectron microscopy,
      demonstrated that this immunoreactivity was due to a concentration of the beta1
      subunit in the endfeet of neuroepithelial and Muller glial cells. Injection of
      collagenase into the vitreous of live embryos, a procedure that selectively
      removes the inner limiting membrane, but does not proteolytically degrade the
      integrin protein, resulted in a redistribution of the integrin immunoreactivity,
      demonstrating that the integrity of the basal lamina is required for the
      maintenance of the concentration of the beta1 subunit in the endfeet. These
      results suggest a role for the beta1 subunit-containing integrin heterodimers in
      the adhesion of neuroepithelial and Muller glial cells to extracellular matrix
      components of the inner limiting membrane, possibly stabilizing the radial
      morphology of these cells.

PMID- 10888746
TI  - Altered development of visual subcortical projections following neonatal thalamic
      ablation in the hamster.
AB  - Previous research has demonstrated that precise patterns of axonal connectivity
      often develop during a series of stages characterized by pathfinding, target
      recognition, and address selection. This last stage involves the focusing of
      projections to a precisely defined region within the target. Because thalamic
      projections begin to innervate cortex before the latter stages are reached, these
      projections may be important in the establishment of adult-like patterns of
      cortical connectivity. To address this issue, we examined the mature
      corticopontine and corticospinal projections of visual cortex deprived of early
      thalamic input by visual thalamic ablation. Although ablations on the day of
      birth in hamsters did not disrupt the targeting of appropriate subcortical
      structures by visual cortical axons, they did alter the organization of
      projections within the basilar pons and spinal cord. The density and spread of
      visual corticopontine connections in lesioned animals was greatly increased
      relative to unlesioned animals, suggesting that thalamic afferents are required
      during address selection, when the topographic specificity of projections is
      established. To determine whether early visual thalamic ablation increases
      connectivity by stabilizing an exuberant developmental projection, we examined
      the normal development of visual corticopontine connections in hamsters ages
      postnatal days 1-17 (P1-P17). From the earliest ages, visual cortical axons
      innervate the pontine nucleus in regions specific to their adult projection zones
      and show progressive growth within these zones. At no time during development do
      projections exist that are equivalent to the projections found after thalamic
      ablation, suggesting that removal of thalamic input does not simply stabilize a
      developmental projection.

PMID- 10888747
TI  - Parallel organization in honey bee mushroom bodies by peptidergic Kenyon cells.
AB  - Antisera against the neuromodulatory peptides, Phe-Met-Arg-Phe-NH(2)-amide
      (FMRFamide) and gastrin cholecystokinin, demonstrate that the mushroom bodies of
      honey bees are subdivided longitudinally into strata. Three-dimensional
      reconstructions demonstrate that these strata project in parallel through the
      entire pedunculus and through the medial and vertical lobes. Immunostaining
      reveals clusters of immunoreactive cell bodies within the calyx cups and
      immunoreactive bundles of axons that line the inside of the calyx cup and lead to
      strata. Together, these features reveal that immunoreactive strata are composed
      of Kenyon cell axons rather than extrinsic elements, as suggested previously by
      some authors. Sorting amongst Kenyon cell axons into their appropriate strata
      already begins in the calyx before these axons enter the pedunculus. The three
      main concentric divisions of each calyx (the lip, collar, and basal ring) are
      divided further into immunoreactive and immunonegative zones. The lip neuropil is
      divided into two discrete zones, the collar neuropil is divided into five zones,
      and the basal ring neuropil is divided into four zones. Earlier studies proposed
      that the lip, collar, and basal ring are represented by three broad bands in the
      lobes: axons from adjacent Kenyon cell dendrites in the calyces are adjacent in
      the lobes even after their polar arrangements in the calyces have been
      transformed to rectilinear arrangements in the lobes. The universality of this
      arrangement is not supported by the present results. Although immunoreactive
      zones are found in all three calycal regions, immunoreactive strata in the lobes
      occur mainly in the two bands that were ascribed previously to the collar and the
      basal ring. In the lobes, immunoreactive strata are visited by the dendrites of
      efferent neurons that carry information from the mushroom bodies to other parts
      of the brain. Morphologically and chemically distinct subdivisions through the
      pedunculus and lobes of honey bees are comparable to longitudinal subdivisions
      demonstrated in the mushroom bodies of other insects, such as the cockroach
      Periplaneta americana. The functional and evolutionary significance of the
      results is discussed.

PMID- 10888748
TI  - Intercellular adhesion molecule expression in ductal carcinoma of the breast:
      correlation of immunohistochemical staining with cytologic smear pattern.
AB  - Recent studies suggest that altered expression of intercellular adhesion
      molecules (ICAM) in ductal carcinoma of the breast is associated with a higher
      incidence of metastases and decreased patient survival. In addition, the presence
      of significant cellular dyscohesion in cytologic smear preparations has been
      found to correlate with the presence of regional and distant metastases in a
      subset of patients. In this study, we correlate the smear pattern in preparations
      taken directly from surgically excised breast tumors with their
      immunohistochemical staining pattern, using antibodies directed against a panel
      of ICAM. We found excellent correlation, as all three tumors with an extremely
      high degree of tumor cell cohesion showed strong staining with all ICAM
      antibodies in the vast majority (>/=90%) of tumor cells in corresponding tissue
      sections. In contrast, five tumors displaying a largely dyscohesive smear pattern
      demonstrated decreased staining (</=70% of tumor cells) with at least one of the
      ICAM antibodies used. Tumors with intermediate degrees of cellular cohesion in
      smear preparations showed varied patterns of ICAM staining. These findings
      support the theory that loss of ICAM expression represents the physiologic basis
      for patterns observed in cytologic smears of ductal carcinoma of the breast.

PMID- 10888749
TI  - Cyclin-dependent kinase inhibitor p27(Kip1) expression in thyroid cells obtained
      by fine-needle aspiration biopsy: a preliminary report.
AB  - Recent studies on paraffin-embedded tissue have shown that the cyclin-dependent
      kinase inhibitor p27(Kip1) is expressed in normal thyroid cells, whereas it is
      downregulated in neoplastic cells. This prospective study was undertaken to
      assess whether p27(Kip1) staining may also be applied to fine-needle aspiration
      biopsy (FNAB) samples of the thyroid. We present here our preliminary results on
      100 FNABs examined for p27(Kip1) expression. p27(Kip1) expression was assessed by
      immunocytochemistry; the technique was optimized on smears prepared from a normal
      thyreocyte cell line (TL5), which conspicuously expresses p27(Kip1), and then
      applied to FNAB samples prospectively collected from 80 cases of nodular goiter
      and 20 cases of thyroid neoplasms (10 papillary carcinomas and 10 follicular
      neoplasms). The TL5 cell culture smears showed that methanol fixation, followed
      by heat-induced antigen retrieval, is the most suitable technique for p27(Kip1)
      staining on cytological samples. The FNAB smears similarly treated showed high
      p27(Kip1) expression (75%) in goiter and a significantly lower expression (35%)
      in neoplasms (P < 0.0001). Our preliminary results show that: 1) p27(Kip1)
      protein expression can be reliably assessed on cytological samples; and 2)
      p27(Kip1) stains nonneoplastic and neoplastic samples in a different fashion, and
      thus is a useful tool in thyroid cytology.

PMID- 10888750
TI  - Analysis of three-dimensional architecture in Feulgen-stained fine-needle liver
      aspirates, using confocal scanning laser microscopy.
AB  - Early and accurate diagnosis of hepatocellular carcinoma in liver nodules using
      fine-needle aspiration biopsy can still pose difficulties, particularly in
      cirrhotic nodules containing dysplastic hepatocytes. Loss of architectural clues,
      which may aid diagnosis, can be overcome by using confocal scanning laser
      microscopic examination of tissue fragments in smears without the need for
      further processing of slides. The basic fuchsin of the Feulgen method resulted in
      excellent confocal images without the need for further processing of the smears.
      Clear morphological differences in three-dimensional reconstructions of optically
      sectioned tissue fragments were demonstrated in normal, hyperplastic, and
      malignant smears as an aid to diagnosis.

PMID- 10888751
TI  - Role of fine-needle aspiration cytology in nonpalpable mammary lesions: a
      comparative cytohistologic study based on 308 cases.
AB  - We retrospectively evaluated the accuracy of fine-needle aspiration cytology
      (FNAC) in nonpalpable breast lesions detected by imaging techniques between 1995
      1997. A total number of 308 lesions was investigated: 273 had been studied by
      means of either FNAC obtained under ultrasound (175 cases) or stereotactic
      guidance (98 cases). The overall sensitivity rate was 87.8%; specificity was
      95.3%; the positive predictive value was 76.6%; the negative predictive value was
      97.8%. Our results confirm that FNAC is quite effective in the approach to
      patients with nonpalpable breast lesions. It is particularly accurate in
      diagnosing malignancy, although a lower yield may be encountered in tumor types
      producing a desmoplastic stroma (tubular carcinoma, infiltrating lobular
      carcinoma) or in noncomedonic in situ ductal carcinoma. Discrepancy between a
      suspicious cytology and a negative histology is more frequent with benign lesions
      usually because of sampling mistake or technically inadequate smears. In
      particular, when smears are adequate, FNAC safely assists in ruling out the
      malignant lesions.

PMID- 10888752
TI  - Cytomorphology of high-grade neuroendocrine carcinoma of the urinary tract.
AB  - High-grade neuroendocrine carcinoma of the bladder is a rare malignant tumor with
      poor prognosis. We present the cytomorphologic features of six retrospectively
      identified cases which displayed high-grade tumors with neuroendocrine
      differentiation in bladder washings. Cytology specimens showed small-to-medium
      sized tumor cells with powdery chromatin, inconspicuous nucleoli, and ill-defined
      nuclear membranes. Tumor fragments showed prominent nuclear molding and single
      cell necrosis. All cases also revealed a varying proportion of tumor cells
      resembling the usual transitional-cell carcinoma. Biopsy specimens from five
      cases demonstrated high-grade transitional-cell carcinoma with areas resembling
      small-cell carcinoma. In one case the entire tumor consisted of classic small
      cell carcinoma and failed to show any areas of transitional-cell differentiation.
      All cases were positive for neuroendocrine markers. Neuroendocrine carcinomas of
      the urinary bladder are rare, with cytological features similar to high-grade
      neuroendocrine carcinomas seen in other organs. They can be accurately diagnosed
      cytologically, and an awareness of the cytomorphologic features is important.

PMID- 10888753
TI  - Rhinocerebral mucormycosis diagnosis by aspiration cytology.
AB  - Rhinocerebral mucormycosis is a rapidly progressing, often fatal fungal infection
      that occurs commonly in diabetics and immunocompromised individuals. We present 2
      cases of rhinocerebral mucormycosis with a paranasal mass. One patient had an
      intracranial extension. Nasal scrapings and fine-needle aspiration cytology
      (FNAC) of the paranasal masses showed fungal hyphae morphologically resembling
      Mucor. Surgical material showed features of mucormycosis. FNAC and scrape smears
      can give a conclusive diagnosis of mucormycosis, and the patient can be treated
      with appropriate antifungal therapy and surgical debridement. Preoperative
      cytology is an effective technique to establish a diagnosis of mucormycosis and
      obviates the need for a preoperative biopsy.

PMID- 10888754
TI  - Aspiration and imprint cytopathology of thyroid carcinoma associated with
      familial adenomatous polyposis.
AB  - Thyroid carcinomas occur in association with familial adenomatous polyposis
      (FAP), and some are the first symptom of FAP. Although several histological
      features have been reported, the cytopathology of FAP-associated thyroid
      carcinoma has not yet been described. We report on two cases of FAP-associated
      thyroid carcinomas diagnosed by fine-needle aspiration biopsy and one case
      imprinted after resection. All 3 patients belonged to the same family, and
      thyroid carcinoma was the first symptom of the proband. Cytological features
      include fascicular or whorl formation of spindle cells with papillary,
      follicular, and/or solid architectures, in addition to the typical features of
      papillary carcinoma. The cytological features of FAP-associated thyroid
      carcinomas are characteristic and may suggest FAP.

PMID- 10888755
TI  - Fine-needle aspiration cytology of acne rosacea.
AB  - Acne rosacea is a common dermatologic condition which is usually diagnosed by its
      clinical presentation. This article describes an unusual presentation of acne
      rosacea and the diagnosis of this condition using fine-needle aspiration biopsy.
      To our knowledge, the fine-needle aspiration findings of acne rosacea have not
      been previously described and illustrated in the cytology literature.

PMID- 10888756
TI  - Diagnosis of recurrent uterine carcinosarcoma by fine-needle aspiration cytology:
      report of a case.
AB  - Uterine carcinosarcomas are uncommon, aggressive neoplasms usually afflicting
      postmenopausal women. Histologically, they are characterized by the presence of
      both malignant epithelial and stromal cells. The latter may be either homologous
      or heterologous in nature. The cytologic diagnosis of carcinosarcoma via fine
      needle aspiration (FNA) was previously described for primary tumors arising in
      the parotid gland, breast, lung, and ovary. Although the diagnosis of uterine
      carcinosarcoma via cervicovaginal, endometrial, and peritoneal fluid cytology has
      been described, the FNA cytology diagnosis of recurrent uterine carcinosarcoma
      has only been rarely described. We present a case of recurrent uterine
      carcinosarcoma in a 59-yr-old woman, diagnosed by ultrasound-guided FNA cytology.
      Cytologic smears showed a biphasic neoplasm consisting of both malignant columnar
      epithelial and spindle cells, in a background of tumor diathesis. This case
      illustrates the diagnostic utility of aspiration cytology in the investigation of
      recurrent carcinosarcoma in clinically suspicious lesions arising postsurgery.

PMID- 10888757
TI  - Desmoplastic ameloblastoma: a case report with fine-needle aspiration cytologic
      findings.
AB  - A case of desmoplastic ameloblastoma of the maxilla in a 25-yr-old woman is
      presented. Smears prepared from fine-needle aspiration cytology showed two
      populations of cellular elements: cohesive epithelial clusters with basaloid
      morphology present, mostly in bidimensional, irregularly outlined clusters with
      ill-formed palisading of nuclei at the periphery in some, and a mesenchymal
      component represented by 1) a sparse chunk of moderate-sized tissue fragments
      made up of spindle- or ovoid-shaped nuclei entrapped in mesenchymal matrix, and
      2) many dissociated naked oval-to-spindle-shaped nuclei. The presence of
      epithelial and mesenchymal components and their benign nature lead us to consider
      the possibility of benign odontogenic tumors 1) of epithelial origin, such as
      ameloblastma with a stromal component, e.g., desmoplastic ameloblastoma; 2) of
      mesenchymal origin, such as odontogenic fibroma; and 3) of mixed epithelial and
      mesenchymal origin, such as ameloblastic fibroma. Excision and histopathological
      examination of this lesion confirmed the diagnosis of desmoplastic ameloblastoma.
      In the given clinical setting and radiological examination, the above cytological
      features suggest a benign odontogenic tumor, rather than precisely diagnosing any
      of the entities mentioned above. However, it is important to distinguish between
      these, since the treatment varies accordingly. The differential diagnosis is
      discussed.

PMID- 10888758
TI  - Small-cell variant of synovial sarcoma: fine-needle aspiration with ancillary
      features and potential diagnostic pitfalls.
AB  - We report a small-cell variant of synovial sarcoma examined by fine-needle
      aspiration (FNA) biopsy. The patient is a 23-yr-old female who had a synovial
      sarcoma involving the left infratemporal region, diagnosed at 7 yr of age,
      followed by a metastatic lesion involving the lung and chest wall 16 yr later.
      The chest wall metastases was sampled by FNA biopsy. The aspirate consisted of
      numerous, small, round cells with very high nuclear-to-cytoplasmic ratios. The
      cytomorphologic features could potentially be confused with other pediatric small
      round cell tumors. Ancillary studies demonstrated positive staining of the
      neoplastic cells for cytokeratin, epithelial membrane antigen (EMA), and CD99.
      The differential diagnosis of other small round cell tumors that may be mistaken
      for the small-cell variant of synovial sarcoma are presented. We believe that
      this is the first FNA report detailing the cytologic and ancillary features of
      the small-cell variant of synovial sarcoma.

PMID- 10888759
TI  - Aspiration cytology of mesoblastic nephroma in an adult: diagnostic dilemma.
AB  - A case of adult mesoblastic nephroma (MN) was erroneously interpreted as a benign
      mesenchymal tumor on fine-needle aspiration (FNA) cytology. MN is a rare tumor in
      infants and is extremely uncommon in adults. A 50-yr-old female presented with a
      renal lump with the clinicoradiological possibility of renal-cell carcinoma.
      Giemsa-stained smears were highly cellular and showed cohesive interlacing
      fragments of spindle cells embedded in abundant pink fibrillary stromal matrix.
      Epithelial component was seen in the form of tubules. Pleomorphism, mitosis, and
      necrosis were absent. Cytologic features in both adult and infantile MN are
      similar, but in an adult can be mistaken for benign or malignant mesenchymal
      tumor and the sarcomatoid variant of renal-cell carcinoma. FNA in such a rare yet
      cytomorphologically characteristic lesion can be helpful in guiding the
      management. Awareness on the part of both the clinician and the cytopathologist
      is necessary to resolve the diagnostic dilemma.

PMID- 10888760
TI  - Can glandular lesions be diagnosed in pap smear cytology?
AB  - Many reports have been published on the accuracy of the cervical vaginal smear
      for squamous lesions, and the literature contains fewer reports on the accuracy
      of the cervical vaginal smear for glandular lesions. The sensitivity of glandular
      lesion diagnosis depends on the subtype of lesion. The diagnostic sensitivity is
      highest for invasive endocervical adenocarcinoma and lowest for endometrial
      adenocarcinoma. The ability of some of the Bethesda system categories for
      glandular lesions to describe what they purport to describe is questionable. The
      Bethesda system categories of adenocarcinoma accurately classify adenocarcinomas.
      The Bethesda System category of atypical glandular cells of undetermined
      significance (AGUS) is a misnomer. Although many cases of adenocarcinoma in-situ
      are placed in this category, follow-up of patients with AGUS show that the
      majority of patients with clinically significant lesions have squamous
      dysplasias. Other categories of AGUS, such as AGUS favor endometrial origin, are
      more appropriately named and encompass endometrial lesions which are either
      neoplastic or non-neoplastic.

PMID- 10888761
TI  - Intraoperative scrape cytology: comparison with frozen sections, using receiver
      operating characteristic (ROC) curve.
AB  - The diagnostic role of intraoperative cytology (IC) has been demonstrated by many
      comparative studies. These studies have used sensitivity and specificity as
      statistical tools, based on binary principles. Statistical methods based on
      binary principles appear to be inappropriate for comparing anatomic pathology
      studies which involve significant human judgment with a range of subjective
      nonbinary result patterns. In this study, we applied the receiver operating
      characteristic (ROC) curve, which is based on probabilistic principles for the
      comparison of diagnostic accuracy with IC and frozen sections (FS). Seven
      observers studied a variable number of IC alone, FS alone, and IC/FS together
      from a pool of 446 specimens. The results were analyzed by ROC curve, using the
      MEDCALC software program (MedCalc Software, Mariakerke, Belgium). The accuracy
      with IC alone and FS alone was comparable. IC alone was diagnostic for many
      lesions, offering the choice of not freezing the tissue, and thus avoiding the
      introduction of artifacts. This strongly favors the routine practice of preparing
      IC during intraoperative consultation.

PMID- 10888762
TI  - Lymphocytic mastopathy in a patient with previous breast cancer diagnosed by fine
      needle aspirate.

PMID- 10888763
TI  - Fine-needle aspiration biopsy cytology of angiosarcoma.

PMID- 10888764
TI  - Cytopathology in Israel.

PMID- 10888765
TI  - Use of immunohistochemistry to search for Helicobacter pylori within the
      appendix.

PMID- 10888766
TI  - Clinician interpretation of pathology reports: confusion or comprehension?

PMID- 10888767
TI  - The total test approach to standardization of immunohistochemistry.

PMID- 10888768
TI  - Designing tumor marker studies: will the results provide clinically useful
      information.

PMID- 10888769
TI  - Baron Guillaume Dupuytren.

PMID- 10888771
TI  - College of American Pathologists Conference XXXV: solid tumor prognostic factors
      which, how and so what? Summary document and recommendations for implementation.
      Cancer Committee and Conference Participants.
AB  - The College of American Pathologists convened a prognostic factor conference in
      June 1999 to consider prognostic and predictive factors in breast, colon, and
      prostate cancer, and to stratify these factors into categories reflecting the
      strength of published evidence. Because so little progress in prognostic factor
      clinical utility has been made in the last 5 years, the conference participants
      focused their attention on decreasing variation in methods, interpretation, and
      reporting of these factors so that greater clarity of value could be achieved.
      The conference was organized to promote discussion, broad input, and future
      planning. An initial plenary session provided an overview of the status of tumor
      marker research, the impact of variation in medicine and pathology, and
      statistical issues related to prognostic factor research. In working group
      sessions for each cancer type, participants interactively evaluated and refined
      the documents created by the expert panels. A second plenary session dealt with
      issues common to all 3 groups, including the problem of micrometastases in lymph
      nodes in these sites; statistical issues that arose during the breakout
      discussions; and issues of variation in methods, interpretation, and reporting of
      immunohistochemical assays. A faculty session brainstormed strategies that could
      be used to implement the changes recommended. This session included invited
      representatives of the Food and Drug Administration, Health Care Financing
      Administration, Centers for Disease Control and Prevention, National Cancer
      Institute, American Joint Committee on Cancer, and International Union Against
      Cancer. Cancer site and general recommendations were presented and discussed
      during a final session to achieve consensus of the conference participants and to
      address feasibility of implementation of these recommendations. A final
      discussion focused on future initiatives that might lead to implementation of the
      changes proposed in the conference by the various organizations represented. This
      report summarizes the general conference recommendations, cancer working group
      recommendations, and plans for implementation of the recommendations.

PMID- 10888772
TI  - Prognostic factors in breast cancer. College of American Pathologists Consensus
      Statement 1999.
AB  - BACKGROUND: Under the auspices of the College of American Pathologists, a
      multidisciplinary group of clinicians, pathologists, and statisticians considered
      prognostic and predictive factors in breast cancer and stratified them into
      categories reflecting the strength of published evidence. MATERIALS AND METHODS:
      Factors were ranked according to previously established College of American
      Pathologists categorical rankings: category I, factors proven to be of prognostic
      import and useful in clinical patient management; category II, factors that had
      been extensively studied biologically and clinically, but whose import remains to
      be validated in statistically robust studies; and category III, all other factors
      not sufficiently studied to demonstrate their prognostic value. Factors in
      categories I and II were considered with respect to variations in methods of
      analysis, interpretation of findings, reporting of data, and statistical
      evaluation. For each factor, detailed recommendations for improvement were made.
      Recommendations were based on the following aims: (1) increasing uniformity and
      completeness of pathologic evaluation of tumor specimens, (2) enhancing the
      quality of data collected about existing prognostic factors, and (3) improving
      patient care. RESULTS AND CONCLUSIONS: Factors ranked in category I included TNM
      staging information, histologic grade, histologic type, mitotic figure counts,
      and hormone receptor status. Category II factors included c-erbB-2 (Her2-neu),
      proliferation markers, lymphatic and vascular channel invasion, and p53. Factors
      in category III included DNA ploidy analysis, microvessel density, epidermal
      growth factor receptor, transforming growth factor-alpha, bcl-2, pS2, and
      cathepsin D. This report constitutes a detailed outline of the findings and
      recommendations of the consensus conference group, organized according to
      structural guidelines as defined.

PMID- 10888773
TI  - Prognostic factors in colorectal cancer. College of American Pathologists
      Consensus Statement 1999.
AB  - BACKGROUND: Under the auspices of the College of American Pathologists, the
      current state of knowledge regarding pathologic prognostic factors (factors
      linked to outcome) and predictive factors (factors predicting response to
      therapy) in colorectal carcinoma was evaluated. A multidisciplinary group of
      clinical (including the disciplines of medical oncology, surgical oncology, and
      radiation oncology), pathologic, and statistical experts in colorectal cancer
      reviewed all relevant medical literature and stratified the reported prognostic
      factors into categories that reflected the strength of the published evidence
      demonstrating their prognostic value. Accordingly, the following categories of
      prognostic factors were defined. Category I includes factors definitively proven
      to be of prognostic import based on evidence from multiple statistically robust
      published trials and generally used in patient management. Category IIA includes
      factors extensively studied biologically and/or clinically and repeatedly shown
      to have prognostic value for outcome and/or predictive value for therapy that is
      of sufficient import to be included in the pathology report but that remains to
      be validated in statistically robust studies. Category IIB includes factors shown
      to be promising in multiple studies but lacking sufficient data for inclusion in
      category I or IIA. Category III includes factors not yet sufficiently studied to
      determine their prognostic value. Category IV includes factors well studied and
      shown to have no prognostic significance. MATERIALS AND METHODS: The medical
      literature was critically reviewed, and the analysis revealed specific points of
      variability in approach that prevented direct comparisons among published studies
      and compromised the quality of the collective data. Categories of variability
      recognized included the following: (1) methods of analysis, (2) interpretation of
      findings, (3) reporting of data, and (4) statistical evaluation. Additional
      points of variability within these categories were defined from the collective
      experience of the group. Reasons for the assignment of an individual prognostic
      factor to category I, II, III, or IV (categories defined by the level of
      scientific validation) were outlined with reference to the specific types of
      variability associated with the supportive data. For each factor and category of
      variability related to that factor, detailed recommendations for improvement were
      made. The recommendations were based on the following aims: (1) to increase the
      uniformity and completeness of pathologic evaluation of tumor specimens, (2) to
      enhance the quality of the data needed for definitive evaluation of the
      prognostic value of individual prognostic factors, and (3) ultimately, to improve
      patient care. RESULTS AND CONCLUSIONS: Factors that were determined to merit
      inclusion in category I were as follows: the local extent of tumor assessed
      pathologically (the pT category of the TNM staging system of the American Joint
      Committee on Cancer and the Union Internationale Contre le Cancer [AJCC/UICC]);
      regional lymph node metastasis (the pN category of the TNM staging system); blood
      or lymphatic vessel invasion; residual tumor following surgery with curative
      intent (the R classification of the AJCC/UICC staging system), especially as it
      relates to positive surgical margins; and preoperative elevation of
      carcinoembryonic antigen elevation (a factor established by laboratory medicine
      methods rather than anatomic pathology). Factors in category IIA included the
      following: tumor grade, radial margin status (for resection specimens with
      nonperitonealized surfaces), and residual tumor in the resection specimen
      following neoadjuvant therapy (the ypTNM category of the TNM staging system of
      the AJCC/UICC). (ABSTRACT TRUNCATED)

PMID- 10888774
TI  - Prognostic factors in prostate cancer. College of American Pathologists Consensus
      Statement 1999.
AB  - BACKGROUND: Under the auspices of the College of American Pathologists, a
      multidisciplinary group of clinicians, pathologists, and statisticians considered
      prognostic and predictive factors in prostate cancer and stratified them into
      categories reflecting the strength of published evidence and taking into account
      the expert opinions of the Prostate Working Group members. MATERIALS AND METHODS:
      Factors were ranked according to the previous College of American Pathologists
      categorical rankings: category I, factors proven to be of prognostic importance
      and useful in clinical patient management; category II, factors that have been
      extensively studied biologically and clinically but whose importance remains to
      be validated in statistically robust studies; and category III, all other factors
      not sufficiently studied to demonstrate their prognostic value. Factors in
      categories I and II were considered with respect to variations in methods of
      analysis, interpretation of findings, reporting of data, and statistical
      evaluation. For each factor, detailed recommendations for improvement were made.
      Recommendations were based on the following aims: (1) increasing uniformity and
      completeness of pathologic evaluation of tumor specimens, (2) enhancing the
      quality of data collected pertaining to existing prognostic factors, and (3)
      improving patient care. RESULTS AND CONCLUSIONS: Factors ranked in category I
      included preoperative serum prostate-specific antigen level, TNM stage grouping,
      histologic grade as Gleason score, and surgical margin status. Category II
      factors included tumor volume, histologic type, and DNA ploidy. Factors in
      category III included perineural invasion, neuroendocrine differentiation,
      microvessel density, nuclear roundness, chromatin texture, other karyometric
      factors, proliferation markers, prostate-specific antigen derivatives, and other
      factors (oncogenes, tumor suppressor genes, apoptosis genes, etc).

PMID- 10888775
TI  - The challenge of variation in medical practice.
AB  - Medicine has been identified as a profession for almost 3000 years based on a
      core premise that physicians have the right to evaluate their own quality.
      Because medicine is a profession and because of the special privileges granted to
      physicians by society, quality-based principles that evolved in the manufacturing
      business have been difficult to adapt to medical practice. Physicians learn from
      other physicians and medical literature. This leads to wide variation in what is
      considered best practice. Variation has complex association, including the
      variation in expert opinion, the complexity of medical knowledge, the variation
      in physician decision-making potential, and human error. Guidelines or algorithms
      are a strategy that are finding favor as a solution. The control of variation
      through guideline development, iterative refinement of guidelines, and feedback
      to physicians will improve medical practice. By removing variation, physicians
      can honor the fiduciary trust that they have made to patients, make reasoned
      decisions, improve outcomes, and focus attention on making medical improvements.

PMID- 10888776
TI  - The oncologic pathology report. Quality by design.
AB  - OBJECTIVE: To review tenets of basic quality assurance and identify opportunities
      for quality improvement in the laboratory assessment of prognostic factors.
      DESIGN: College of American Pathologists Q-Probes data obtained from hundreds of
      American laboratories throughout the 1990s are used to illustrate laboratory
      performance and practice opportunities in the preanalytic, analytic, and
      postanalytic phases of the total testing process. RESULTS: A wide range of
      performance deficiencies are documented, most in the preanalytic and postanalytic
      phases, and contributed by individuals outside and not under the control of the
      laboratory. In the analytic phase, the effectiveness of checklists on the content
      and completeness of reported diagnostic and prognostic data for breast and colon
      cancers is proven. CONCLUSIONS: In the preanalytic phase, marked enhancements in
      quality would result from improvements in (1) patient and specimen
      identification, (2) adherence to patient-sampling and specimen-handling
      requirements, and (3) communication to the laboratory of the pertinent clinical
      context of the individual test. Once basic analytic quality control and
      laboratory quality assurance issues are resolved, a focus on standardization and
      enhancement of preanalytic and postanalytic communications and satisfaction of
      clinical expectations becomes the source of improved laboratory performance.

PMID- 10888777
TI  - Statistical issues in tumor marker studies.
AB  - CONTEXT: Inferences from tumor marker studies are complicated by a variety of
      statistical concerns, which can make proper interpretation of results difficult.
      This article focuses on important issues that should be addressed when designing,
      conducting, and analyzing tumor marker studies. OBJECTIVE: To highlight the
      importance of considering statistical significance, risk ratios, statistical
      power, reproducibility, multiple testing, confirmatory studies, and missing data
      in the design of marker studies used for prognosis. RESULTS: Suggestions are
      provided for more effectively conducting marker studies. These include more
      careful attention to adequacy of the number of subjects for a marker study and
      improved documentation and standardization of assay methods. The importance of
      complete reporting of study results and description of the statistical analysis
      methods used is also emphasized. CONCLUSION: Cooperation among clinicians,
      laboratory scientists, and statisticians will be required to conduct
      statistically sound tumor marker studies and to facilitate prioritizing markers
      for new and confirmatory studies in an environment of limited patient and
      specimen resources.

PMID- 10888778
TI  - Updated protocol for the examination of specimens from patients with carcinomas
      of the colon and rectum, excluding carcinoid tumors, lymphomas, sarcomas, and
      tumors of the vermiform appendix: a basis for checklists. Cancer Committee.

PMID- 10888779
TI  - Updated protocol for the examination of specimens from patients with carcinomas
      of the breast. Cancer Committee.

PMID- 10888780
TI  - Updated protocol for the examination of specimens from patients with carcinomas
      of the prostate gland: a basis for checklists. Cancer Committee.

PMID- 10888781
TI  - Clinicians are from Mars and pathologists are from Venus.
AB  - CONTEXT: Text reports convey critical medical information from pathologists,
      radiologists, and subspecialty consultants. These reports must be clear and
      comprehensible to avoid medical errors. Pathologists have paid much attention to
      report completeness but have ignored the corresponding issue of report
      comprehension. This situation presents an increasingly serious potential problem.
      As laboratories are consolidated and as reports are disseminated in new ways (eg,
      via the World Wide Web), the target audience becomes more diverse and less likely
      to have any contact with pathologists beyond the written reports themselves.
      OBJECTIVE: To compare clinician comprehension with pathologist intent in written
      pathology reports. METHODS: Typical surgical pathology reports relevant to
      surgeons and covering a range of specimen complexity were taken from our hospital
      files. Questionnaires based on these cases were administered open-book
      examination style to surgical attending physicians and trainees during surgical
      conferences at an academic medical center. MAIN OUTCOME MEASURES: Scores from
      questionnaires. RESULTS: Surgeons misunderstood pathologists' reports 30% of the
      time. Surgical experience reduced but did not eliminate the problem. Streamlined
      report formatting exacerbated the problem. CONCLUSIONS: A communication gap
      exists between pathologists and surgeons. Familiarity with report format and
      clinical experience help reduce this gap. Paradoxically, stylistic improvements
      to report formatting can interfere with comprehension and increase the number of
      misunderstandings. Further investigation is required to reduce the number of
      misunderstandings and, thus, medical errors.

PMID- 10888782
TI  - Urinary cytologic findings in patients with benign and malignant adenomatous
      polyps of the prostatic urethra.
AB  - CONTEXT: Urethral adenomatous polyps with prostatic epithelium (also known as
      benign prostatic epithelial polyps [BPEPs]) are a documented cause of hematuria,
      dysuria, and hematospermia, conditions that may prompt cytologic evaluation of
      urine. DESIGN: The urine cytologic test findings in 5 cases of biopsy-proven
      BPEPs and in 1 case of prostatic ductal adenocarcinoma (PDA) that presented as a
      urethral polyp were retrospectively evaluated. Immunocytochemical stain for
      prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and high
      molecular-weight cytokeratin (34betaE12) were used in evaluation of the lesions.
      RESULTS: In 4 of 5 cases of BPEPs, clusters of bland columnar cells with uniform,
      oval nuclei were seen. Positive immunostaining for PSA and PAP confirmed the
      prostatic origin of the clusters in 2 cases. One urine sample contained abundant
      goblet cells and extracellular mucin, consistent with intestinal metaplasia
      coexisting in the bladder biopsy specimen. The urine sample in the fifth case of
      BPEPs contained no columnar cells. The last case had multiple urine cytologic
      evaluations that demonstrated PSA-positive, malignant-appearing clusters of
      columnar cells. A biopsy specimen of the polyps was described as a high-grade
      prostatic intraepithelial neoplasm in adenomatous polyp. However, in this
      patient, PDA was diagnosed on transurethral resection of the prostate specimen 4
      years after the initial urine cytologic test. CONCLUSION: Benign prostatic
      epithelial polyps should be considered in the differential diagnosis of clusters
      of columnar cells in urine cytologic testing. Cells with malignant nuclear
      features should instigate a careful search for a (prostatic) neoplasm, which may
      present as urethral polyps (e.g., PDA). Stains for PSA or PAP are useful adjuncts
      in differential diagnosis of this condition.

PMID- 10888783
TI  - Breast carcinoma presenting during or shortly after pregnancy and lactation.
AB  - CONTEXT: Much has been written about the clinical management and prognosis of
      breast carcinomas presenting during pregnancy and lactation, yet little is known
      about the detailed histopathology of these tumors. OBJECTIVE: To determine
      whether these carcinomas have any specific diagnostic features. DESIGN: A
      detailed histologic and immunohistochemical study of 14 cases of breast carcinoma
      presenting during or shortly after pregnancy or lactation was conducted. The
      findings were compared with a control group of 13 tumors developing in age
      matched women with no recent history of pregnancy or lactation. SETTING: The
      histopathology department of a tertiary referral teaching hospital. RESULTS:
      Tumors in the pregnancy/lactation group had a significantly higher incidence of
      cancerization of lobules (79% vs 15%) and of grade III invasive ductal carcinomas
      (80% vs 33%). Tumors occurring during lactation were either totally or partly
      mucinous and were MUC2 positive. Tumors occurring during pregnancy, but not
      during lactation, were mostly estrogen and progesterone receptor negative (4/5
      and 5/5, respectively). All tumors occurring during pregnancy and lactation that
      were tested for c-erbB-2 overexpression were negative, whereas all 4 tumors
      tested that occurred shortly after delivery or cessation of lactation were
      positive for c-erbB-2 overexpression. The incidence of axillary lymph node
      metastasis was high in both the study and control groups, although it was
      slightly higher in the control group (78% and 90%, respectively). CONCLUSIONS:
      Although breast carcinomas diagnosed during or shortly after pregnancy and
      lactation have features in common with those developing in women of similar ages,
      particularly with respect to a high incidence of lymph node metastasis, the
      findings of this study suggest that they may also have distinct morphologic and
      immunohistochemical features of their own. Such features may vary according to
      whether the patient was pregnant, lactating, or had recently terminated her
      pregnancy or lactation at the time of surgical excision. Examination of more
      cases would help confirm these findings.

PMID- 10888784
TI  - Increased expression of vascular endothelial growth factor and angiogenesis in
      the early stage of multistep hepatocarcinogenesis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is known to receive its blood supply
      principally from the hepatic arteries. Recent studies have reported differences
      in the vascular supply, especially arterial supply among low- and high-grade
      dysplastic nodules (DNs) (also referred to as adenomatous hyperplasia and
      macroregenerative nodules) and HCCs. Increased expression of vascular endothelial
      growth factor (VEGF) has been reported in HCC. In addition, VEGF may play an
      important role in the early phases of hepatocarcinogenesis. METHODS: We
      immunohistochemically stained 7 low-grade DNs, 8 high-grade DNs, 11 early HCCs,
      17 small HCCs, and 21 advanced HCCs with antibodies against VEGF, alpha-smooth
      muscle actin (to identify unpaired arteries, ie, arteries not accompanied by bile
      ducts, indicative of angiogenesis), CD34 (as a marker of sinusoidal
      capillarization), and proliferation cell nuclear antigen. RESULTS: Expression of
      VEGF was found in the hepatocytes and HCC cells. The degree of VEGF expression
      increased gradually according to the stepwise development of
      hepatocarcinogenesis. It was higher in high-grade DNs and early HCCs than in low
      grade DNs. The hepatocytes and HCC cells adjacent to peliosis and fibrous septa
      showed stronger VEGF expression. Angiogenesis, unpaired arteries, and sinusoidal
      capillarization developed from low-grade DNs and gradually increased. It was
      highest in HCCs. The proliferation cell nuclear antigen labeling indexes of
      hepatocytes and HCC cells also increased gradually as hepatocarcinogenesis
      progressed. Small HCCs showed a higher status of neoangiogenesis and cell
      proliferation activity than advanced HCCs. The degree of VEGF expression was
      correlated with angiogenesis and cell proliferation activity. CONCLUSION: We
      conclude that VEGF plays a significant role in angiogenesis, growth, and
      development of HCC.

PMID- 10888785
TI  - Improvement in physician's office laboratory practices, 1989-1994.
AB  - BACKGROUND: In 1986 and 1989, the Centers for Disease Control and Prevention
      sponsored institutes on Critical Issues in Health Laboratory Practice. It was
      noted during the institutes that physician's office laboratories were a rapidly
      emerging site for clinical laboratory testing, yet no comprehensive data were
      available regarding the practice of clinical laboratory medicine in physician's
      office laboratories. As a mechanism to begin addressing this void, the Centers
      for Disease Control and Prevention added questions on clinical laboratory
      practice to the National Ambulatory Medical Care Survey, a national probability
      sample of ambulatory care provided by office-based physicians. Data were
      collected for survey years 1989, 1991, 1993, and 1994. METHODS: Each survey was
      conducted among a nationally representative, random sample of office-based
      physicians who provide ambulatory patient care. Sample physicians were enlisted
      using both mail and telephone contacts. Clinical laboratory data were obtained
      via telephone by trained field representatives. Weighted univariate and
      multivariate analyses were performed on responses from each of the 4 survey
      years. Analyses were repeated after combining survey responses from years 1989
      and 1991 and 1993 and 1994 as representative of physician's office laboratory
      practices before and after implementation of the Clinical Laboratory Improvement
      Amendments of 1988 (CLIA '88) final rule in 1992. RESULTS: Quality laboratory
      practice indicators showed significant increases during the study interval, with
      implementation of the CLIA '88 final rule in 1992 playing a pivotal role.
      Relative to 1992, enrollment in proficiency testing programs increased from 32.4%
      to 52.7% (P<.001), use of daily quality control samples increased from 79.2% to
      89.0% (P<.001), and use of daily quality control with written instructions for
      action following a questionable quality control result (quality control with
      action step documentation) increased from 62.6% to 77.2% (P<.001). The presence
      of a medical technologist or technician in the office laboratory was also
      significantly and independently associated with each of the quality indicators.
      Although the percentage of physician's offices performing on-site testing
      decreased from 56% to 45% during the survey interval, overall testing volume
      appeared unchanged. CONCLUSIONS: The quality of clinical laboratory practice in
      physician's office laboratories improved during the study interval (1989-1994) as
      measured by the quality indicators used in the study. The association of this
      improvement with implementation of the CLIA '88 final rule and the presence of a
      trained laboratory professional in the testing site indicate the importance of
      minimum practice standards and professional expertise in ensuring use of quality
      laboratory practices. Overall test volume appeared to be stable despite a
      decreased proportion of physician's offices at which on-site testing was
      performed.

PMID- 10888786
TI  - Recurrent prostate carcinoma presenting as omental large cell carcinoma with
      neuroendocrine differentiation and resulting in bowel obstruction.
AB  - Neuroendocrine differentiation in the neoplastic prostate varies from foci of
      adenocarcinoma showing immunoreactivity to the pure small cell carcinoma, which
      correlates with poor prognosis. Widely metastatic disease in unusual sites is
      reported for small cell carcinoma, and rarely is the serum prostate-specific
      antigen level elevated. We report a case of recurrent prostate adenocarcinoma
      presenting as bowel obstruction due to widespread metastatic disease in the
      omentum and peritoneum. The histopathology of the omental metastasis was that of
      a large cell neuroendocrine carcinoma, without evidence of an adenocarcinoma. The
      absence of a clinically evident second primary tumor, the concomitant elevated
      serum prostate-specific antigen level, and the positive tissue immunoreactivities
      to prostatic markers all supported the prostatic origin of the omental tumor.
      Review of the importance of prostatic neuroendocrine differentiation and its
      unusual metastatic patterns is presented.

PMID- 10888787
TI  - Malignant mesothelioma with CD30-positivity. A case report and review of the
      literature.
AB  - The activation marker CD3O is useful in the diagnosis of Hodgkin and non-Hodgkin
      lymphomas. It has also been described in nonhematopoietic tumors, including
      pancreatic carcinomas, salivary gland tumors, and embryonal carcinomas. We report
      a case of malignant mesothelioma with intense CD30 positivity. This finding has
      not previously been described and is important in broadening the differential
      diagnosis of a CD30(+) cohesive large cell malignancy.

PMID- 10888788
TI  - Identification of female cells in postcoital penile swabs using fluorescence in
      situ hybridization.
AB  - Traditionally, the finding of semen, that is, spermatozoa and acid phosphatase,
      in cervicovaginal specimens has been considered the laboratory evidence needed to
      prove recent sexual contact. Recent research with fluorescence in situ
      hybridization (FISH) has shown that in the absence of semen, male epithelial and
      inflammatory cells can be found within the female genital tract. A striking
      paucity of literature exists pertaining to the examination of the penis of an
      alleged assailant for potential evidence indicative of sexual assault. The
      current study uses FISH to analyzepostcoital swabs of the penis for such
      laboratory evidence. A male and female volunteer couple consented to participate
      in this study. Following coitus, the male partner presented to one of the
      investigators for penile swabbing. Swabs were taken at varying postcoital
      intervals (1-24 hours) subsequent to 10 coital episodes. The male participant was
      instructed not to shower following coitus, but to otherwise go about daily
      activities until specimen collection. To obtain each sample, 4 sterile cotton
      tipped applicators were slightly moistened in sterile saline and swabbed along
      the length of the penile shaft and around the base of the penis. From the swabs,
      3 air-dried slides were prepared, coded, and blinded. As controls, swabs were
      taken from the buccal surfaces of both volunteers. Multicolor FISH was performed
      using dual X- and Y-chromosome probes, and slides were counterstained with 4'-6
      diamidino-2-phenylindole (DAPI). Cells were easily visualized under a fluorescent
      microscope, but only cells with 2 nonoverlapping fluorescent signals were
      counted. Fluorescence in situ hybridization is highly sensitive and specific, and
      the dual probes easily distinguished between male and female cells. Female cells
      were identified on smears from every penile swab over the entire 1- to 24-hour
      postcoital interval. The FISH technique, previously successful in identifying
      male cells within the female genital tract, may also be employed on penile swabs.
      Once the presence of female cells is confirmed by FISH, the identity of the
      female can be confirmed by DNA analysis. Potentially, with such current molecular
      analyses, both the assailant and the victim can be positively identified.

PMID- 10888789
TI  - Isolation and identification of male and female DNA on a postcoital condom.
AB  - BACKGROUND: Identification of male perpetrators of sexual assault may be made
      from cells and fluids recovered from postcoital condoms. To date, the focus has
      been on identifying the person who had worn the condom. OBJECTIVE: To describe a
      method for scientifically identifying both the male and female participants in a
      sex act by employing polymerase chain reaction-based technology on swabs taken
      from the internal and external surfaces of a condom. Fluorescence in situ
      hybridization may be used to screen for the presence of female cells on a condom.
      METHODS: Swabs were taken from the internal and external surfaces of a condom 8
      hours postcoitus. DNA was isolated from each swab through standard organic
      extraction. Extracted DNA was amplified for 8 different genetic loci using the
      Promega PowerPlex kit and the sex identification amelogenin marker. Amplified
      samples were electrophoresed on precast sequencing gels and analyzed
      fluorescently using a Hitachi FMBIO 2 fluorescent scanner and software. Each DNA
      sample obtained from the condom was compared with male and female buccal
      controls. At the time of collection, air-dried slides were prepared from the
      swabs for subsequent multicolor fluorescence in situ hybridization using dual X-
      and Y-chromosome probes with 4'-6-diamidino-2-phenylindole (DAPI)
      counterstaining. RESULTS: A pure sample of female DNA was isolated from the
      external surface of the condom as determined by exclusive amplification of the X
      chromosome-specific 212-base pair amelogenin marker. Swabs taken from the
      internal surface yielded DNA originating from the male participant.
      Identification was conclusive at 8 of 8 genetic loci. Fluorescence in situ
      hybridization identified pure populations of male epithelial cells from the
      internal surface of the condom and female cells from the external surface.
      CONCLUSIONS: Cells shed from a female during sexual intercourse can be retrieved
      from the external surface of a condom following sexual intercourse. Fluorescence
      in situ hybridization can be used to screen for the presence of female cells, and
      positive identification of the female sexual partner can then be made using
      polymerase chain reaction-based methods. We suggest that swabs taken from both
      surfaces of a condom used during sexual assault may be used to provide
      information that will definitively link the victim to the suspect.

PMID- 10888790
TI  - Pathologic quiz case: recurrent hypercalcemia.

PMID- 10888791
TI  - Pathologic quiz case: abdominal pain.

PMID- 10888792
TI  - Getting it together.

PMID- 10888793
TI  - What price e.commerce?

PMID- 10888794
TI  - The promise and perils of criminal DNA databanking.

PMID- 10888795
TI  - The precautionary principle.

PMID- 10888798
TI  - First Finnish biotech IPO.

PMID- 10888796
TI  - The precautionary principle.

PMID- 10888800
TI  - GMO roundup.

PMID- 10888799
TI  - Pioneer settles for $100 M.

PMID- 10888801
TI  - British Biotech downsizes.

PMID- 10888803
TI  - Xenotransplantation regs.

PMID- 10888802
TI  - DeveloGen/HepaVec deal.

PMID- 10888805
TI  - Non-GM futures.

PMID- 10888804
TI  - CuraGen launches subsid.

PMID- 10888807
TI  - Research collaborations.

PMID- 10888806
TI  - UPenn ends IHGT trials.

PMID- 10888808
TI  - Gene therapy proposals.

PMID- 10888810
TI  - From skin to bone.

PMID- 10888809
TI  - Swallowtails unaffected by Bt toxin.

PMID- 10888812
TI  - Arabidopsis database.

PMID- 10888811
TI  - Cells repair spinal cord.

PMID- 10888814
TI  - Pathway shuffling.

PMID- 10888813
TI  - Biocatalytic success.

PMID- 10888815
TI  - Getting down to the essentials.

PMID- 10888816
TI  - Homing in on homeogenes.

PMID- 10888817
TI  - The importance of being three-dimensional.

PMID- 10888818
TI  - A paper boon?

PMID- 10888819
TI  - Engineering toxin-gobbling bacterium.

PMID- 10888820
TI  - Modeling cell death.

PMID- 10888821
TI  - Boosting plant immunity.

PMID- 10888823
TI  - Directed evolution for T-cell receptor stability.

PMID- 10888825
TI  - Single-cell nanoprobes.

PMID- 10888824
TI  - Review.

PMID- 10888826
TI  - EC struggles to unravel regulations.

PMID- 10888827
TI  - Physician proposals could cost biotechs thousands.

PMID- 10888828
TI  - China's efforts to lure biotechs to bio-island criticized.

PMID- 10888830
TI  - Human Research Protections Office created.

PMID- 10888829
TI  - US plans to protect clinical research participants.

PMID- 10888831
TI  - Hatch-waxman changes debated.

PMID- 10888832
TI  - Guilford acquires Gliatech in strategic deal.

PMID- 10888833
TI  - Haplotyping by force.

PMID- 10888834
TI  - A tissue of T cells.

PMID- 10888835
TI  - Aneuploidy--it's more common than you think.

PMID- 10888836
TI  - Death by numbers.

PMID- 10888837
TI  - Deals that make sense.

PMID- 10888838
TI  - Replicative adenoviruses for cancer therapy.
AB  - Rapid advances are being made in the engineering of replication-competent viruses
      to treat cancer. Adenovirus is a mildly pathogenic human virus that propagates
      prolifically in epithelial cells, the origin of most human cancers. While
      virologists have revealed many details about its molecular interactions with the
      cell, applied scientists have developed powerful technologies to genetically
      modify or regulate every viral protein. In tandem, the limited success of
      nonreplicative adenoviral vectors in cancer gene therapy has brought the old
      concept of adenovirus oncolysis back into the spotlight. Major efforts have been
      directed toward achieving selective replication by the deletion of viral
      functions dispensable in tumor cells or by the regulation of viral genes with
      tumor-specific promoters. However, the predicted replication selectivity has not
      been realized because of incomplete knowledge of the complex virus-cell
      interactions and the leakiness of cellular promoters in the viral genome. Capsid
      modifications are being developed to achieve tumor targeting and enhance
      infectivity. Cellular and viral functions that confer greater oncolytic potency
      are also being elucidated. Ultimately, the interplay of the virus with the immune
      system will likely dictate the success of this approach as a cancer therapy.

PMID- 10888839
TI  - Efficient generation of human T cells from a tissue-engineered thymic organoid.
AB  - Biocompatible inorganic matrices have been used to enhance bone repair by
      integrating with endogenous bone architecture. Hypothesizing that a three
      dimensional framework might support reconstruction of other tissues as well, we
      assessed the capacity of a tantalum-coated carbon matrix to support
      reconstitution of functioning thymic tissue. We engineered a thymic organoid by
      seeding matrices with murine thymic stroma. Co-culture of human bone marrow
      derived hematopoietic progenitor cells within this xenogeneic environment
      generated mature functional T cells within 14 days. The proportionate T-cell
      yield from this system was highly reproducible, generating over 70% CD3+ T cells
      from either AC133+ or CD34+ progenitor cells. Cultured T cells expressed a high
      level of T-cell receptor excision circles (TREC), demonstrating de novo T
      lymphopoiesis, and function of fully mature T cells. This system not only
      facilitates analysis of the T-lymphopoietic potential of progenitor cell
      populations; it also permits ex vivo genesis of T cells for possible applications
      in treatment of immunodeficiency.

PMID- 10888841
TI  - TnAraOut, a transposon-based approach to identify and characterize essential
      bacterial genes.
AB  - Identification of genes that encode essential products provides a promising
      approach to validation of new antibacterial drug targets. We have developed a
      mariner-based transposon, TnAraOut, that allows efficient identification and
      characterization of essential genes by transcriptionally fusing them to an
      outward-facing, arabinose-inducible promoter, PBAD, located at one end of the
      transposon. In the absence of arabinose, such TnAraOut fusion strains display
      pronounced growth defects. Of a total of 16 arabinose-dependent TnAraOut mutants
      characterized in Vibrio cholerae, four were found to carry insertions upstream of
      known essential genes (gyrB, proRS, ileRS, and aspRS) whereas the other strains
      carried insertions upstream of known and hypothetical genes not previously shown
      to encode essential gene products. One of the essential genes identified by this
      analysis appears to be unique to V. cholerae and thus may represent an example of
      a species-specific drug target.

PMID- 10888840
TI  - Prevention of systemic lupus erythematosus in MRL/lpr mice by administration of
      an immunoglobulin-binding peptide.
AB  - Systemic lupus erythematosus (SLE) is a multisystem chronic inflammatory disease
      of unknown etiology that affects many organs, including the kidney. The presence
      of multiple autoantibodies and other immunological abnormalities point to basic
      defects in immunoregulatory controls that normally maintain self-tolerance. The
      deposition on kidney tissue of autoantibodies as immune complexes (ICs) through
      the interaction with Fc-receptor gamma-chains is thought to trigger an
      inflammatory response typical of SLE, leading to glomerulonephritis. Using
      combinatorial chemistry approaches, we have identified a peptide able to bind to
      immunoglobulins and to interfere with Fcgamma-receptor recognition.
      Administration of this peptide to MRL/lpr mice, an animal model used to study
      SLE, resulted in a remarkable enhancement of the survival rate (80%) compared to
      placebo-treated animals (10%). Consistent with this was a significant reduction
      of proteinuria, a clinical sign of SLE. Kidney histological examination of
      treated animals confirmed the preservation of tissue integrity and a remarkable
      reduction in IC deposition. These results support the role of Fcgamma receptors
      in SLE pathogenesis and open new avenues for the development of drugs to treat
      autoimmune disorders.

PMID- 10888842
TI  - An induction gene trap for identifying a homeoprotein-regulated locus.
AB  - An important issue in developmental biology is the identification of homeoprotein
      target genes. We have developed a strategy based on the internalization and
      nuclear addressing of exogenous homeodomains, using an engrailed homeodomain
      (EnHD) to screen an embryonic stem (ES) cell gene trap library. Eight integrated
      gene trap loci responded to EnHD. One is within the bullous pemphigoid antigen 1
      (BPAG1) locus, in a region that interrupts two neural isoforms. By combining in
      vivo electroporation with organotypic cultures, we show that an already
      identified BPAG1 enhancer/promoter is differentially regulated by homeoproteins
      Hoxc-8 and Engrailed in the embryonic spinal cord and mesencephalon. This
      strategy can therefore be used for identifying and mutating homeoprotein targets.
      Because homeodomain third helices can internalize proteins, peptides,
      phosphopeptides, and antisense oligonucleotides, this strategy should be
      applicable to other intracellular targets for characterizing genetic networks
      involved in a large number of physiopathological states.

PMID- 10888843
TI  - Molecular breeding of carotenoid biosynthetic pathways.
AB  - The burgeoning demand for complex, biologically active molecules for medicine,
      materials science, consumer products, and agrochemicals is driving efforts to
      engineer new biosynthetic pathways into microorganisms and plants. We have
      applied principles of breeding, including mixing genes and modifying catalytic
      functions by in vitro evolution, to create new metabolic pathways for
      biosynthesis of natural products in Escherichia coli. We expressed shuffled
      phytoene desaturases in the context of a carotenoid biosynthetic pathway
      assembled from different bacterial species and screened the resulting library for
      novel carotenoids. One desaturase chimera efficiently introduced six rather than
      four double bonds into phytoene, to favor production of the fully conjugated
      carotenoid, 3, 4,3',4'-tetradehydrolycopene. This new pathway was extended with a
      second library of shuffled lycopene cyclases to produce a variety of colored
      products. One of the new pathways generates the cyclic carotenoid torulene, for
      the first time, in E. coli. This combined approach of rational pathway assembly
      and molecular breeding may allow the discovery and production, in simple
      laboratory organisms, of new compounds that are essentially inaccessible from
      natural sources or by synthetic chemistry.

PMID- 10888844
TI  - Directed evolution of a stable scaffold for T-cell receptor engineering.
AB  - Here we have constructed a single-chain T-cell receptor (scTCR) scaffold with
      high stability and soluble expression efficiency by directed evolution and yeast
      surface display. We evolved scTCRs in parallel for either enhanced resistance to
      thermal denaturation at 46 degrees C, or improved intracellular processing at 37
      degrees C, with essentially equivalent results. This indicates that the
      efficiency of the consecutive kinetic processes of membrane translocation,
      protein folding, quality control, and vesicular transport can be well predicted
      by the single thermodynamic parameter of thermal stability. Selected mutations
      were recombined to create an scTCR scaffold that was stable for over an hour at
      65 degrees C, had solubility of over 4 mg ml(-1), and shake-flask expression
      levels of 7.5 mg l(-1), while retaining specific ligand binding to peptide-major
      histocompatibility complexes (pMHCs) and bacterial superantigen. These properties
      are comparable to those for stable single-chain antibodies, but are markedly
      improved over existing scTCR constructs. Availability of this scaffold allows
      engineering of high-affinity soluble scTCRs as antigen-specific antagonists of
      cell-mediated immunity. Moreover, yeast displaying the scTCR formed specific
      conjugates with antigen-presenting cells (APCs), which could allow development of
      novel cell-to-cell selection strategies for evolving scTCRs with improved binding
      to various pMHC ligands in situ.

PMID- 10888845
TI  - Direct haplotyping of kilobase-size DNA using carbon nanotube probes.
AB  - We have implemented a method for multiplexed detection of polymorphic sites and
      direct determination of haplotypes in 10-kilobase-size DNA fragments using single
      walled carbon nanotube (SWNT) atomic force microscopy (AFM) probes. Labeled
      oligonucleotides are hybridized specifically to complementary target sequences in
      template DNA, and the positions of the tagged sequences are detected by direct
      SWNT tip imaging. We demonstrated this concept by detecting streptavidin and
      IRD800 labels at two different sequences in M13mp18. Our approach also permits
      haplotype determination from simple visual inspection of AFM images of individual
      DNA molecules, which we have done on UGT1A7, a gene under study as a cancer risk
      factor. The haplotypes of individuals heterozygous at two critical loci, which
      together influence cancer risk, can be easily and directly distinguished from AFM
      images. The application of this technique to haplotyping in population-based
      genetic disease studies and other genomic screening problems is discussed.

PMID- 10888846
TI  - Antibody-based nanoprobe for measurement of a fluorescent analyte in a single
      cell.
AB  - We report here the application of an antibody-based nanoprobe for in situ
      measurements of a single cell. The nanoprobe employs antibody-based receptors
      targeted to a fluorescent analyte, benzopyrene tetrol (BPT), a metabolite of the
      carcinogen benzo[a]pyrene (BaP) and of the BaP-DNA adduct. Detection of BPT is of
      great biomedical interest, since this species can serve as a biomarker for
      monitoring DNA damage due to BaP exposure and for possible precancer diagnosis.
      The measurements were performed on the rat liver epithelial clone 9 cell line,
      which was used as the model cell system. Before making measurements, the cells
      were treated with BPT. Nanoprobes were inserted into individual cells, incubated
      5 min to allow antigen-antibody binding, and then removed for fluorescence
      detection. We determined a concentration of 9.6+/-0.2x10(-11) M for BPT in the
      individual cells investigated. The results demonstrate the possibility of in situ
      measurements inside a single cell using an antibody-based nanoprobe.

PMID- 10888847
TI  - A mathematical model of caspase function in apoptosis.
AB  - Caspases (cysteine-containing aspartate-specific proteases) are at the core of
      the cell's suicide machinery. These enzymes, once activated, dismantle the cell
      by selectively cleaving key proteins after aspartate residues. The events
      culminating in caspase activation are the subject of intense study because of
      their role in cancer, and neurodegenerative and autoimmune disorders. Here we
      present a mechanistic mathematical model, formulated on the basis of newly
      emerging information, describing key elements of receptor-mediated and stress
      induced caspase activation. We have used mass-conservation principles in
      conjunction with kinetic rate laws to formulate ordinary differential equations
      that describe the temporal evolution of caspase activation. Qualitative
      strategies for the prevention of caspase activation are simulated and compared
      with experimental data. We show that model predictions are consistent with
      available information. Thus, the model could aid in better understanding caspase
      activation and identifying therapeutic approaches promoting or retarding
      apoptotic cell death.

PMID- 10888848
TI  - Aerobic degradation of tetrachloroethylene by toluene-o-xylene monooxygenase of
      Pseudomonas stutzeri OX1.
AB  - Tetrachloroethylene (PCE) is thought to have no natural source, so it is one of
      the most difficult contaminants to degrade biologically. This common groundwater
      pollutant was thought completely nonbiodegradable in the presence of oxygen. Here
      we report that the wastewater bacterium Pseudomonas stutzeri OX1 degrades
      aerobically 0. 56 micromol of 2.0 micromol PCE in 21 h (Vmax approximately 2.5
      nmol min(-1) mg(-1) protein and KM approximately 34 microM). These results were
      corroborated by the generation of 0.48 micromol of the degradation product,
      chloride ions. This degradation was confirmed to be a result of expression of
      toluene-o-xylene monooxygenase (ToMO) by P. stutzeri OX1, since cloning and
      expressing this enzyme in Escherichia coli led to the aerobic degradation of 0.19
      micromol of 2.0 micromol PCE and the generation of stoichiometric amounts of
      chloride. In addition, PCE induces formation of ToMO, which leads to its own
      degradation in P. stutzeri OX1. Degradation intermediates reduce the growth rate
      of this strain by 27%.

PMID- 10888849
TI  - Overproduction of salicylic acid in plants by bacterial transgenes enhances
      pathogen resistance.
AB  - After a hypersensitive response to invading pathogens, plants show elevated
      accumulation of salicylic acid (SA), induced expression of plant defense genes,
      and systemic acquired resistance (SAR) to further infection by a broad range of
      pathogens. There is compelling evidence that SA plays a crucial role in
      triggering SAR. We have transformed tobacco with two bacterial genes coding for
      enzymes that convert chorismate into SA by a two-step process. When the two
      enzymes were targeted to the chloroplasts, the transgenic (CSA, constitutive SA
      biosynthesis) plants showed a 500- to 1,000-fold increased accumulation of SA and
      SA glucoside compared to control plants. Defense genes, particularly those
      encoding acidic pathogenesis-related (PR) proteins, were constitutively expressed
      in CSA plants. This expression did not affect the plant phenotype, but the CSA
      plants showed a resistance to viral and fungal infection resembling SAR in
      nontransgenic plants.

PMID- 10888850
TI  - Increased gibberellin biosynthesis in transgenic trees promotes growth, biomass
      production and xylem fiber length.
AB  - In most tree-breeding programs worldwide, increasing the trees' growth rates and
      stem volumes and shortening their rotation times are important aims. Such trees
      would yield more biomass per unit area. Here we show that overexpressing a key
      regulatory gene in the biosynthesis of the plant hormone gibberellin (GA) in
      hybrid aspen (Populus tremula x P. tremuloides) improves growth rate and biomass.
      In addition, these transgenic trees have more numerous and longer xylem fibers
      than unmodified wild-type (wt) plants. Long fibers are desirable in the
      production of strong paper, but it has not as yet proved possible to influence
      this trait by traditional breeding techniques. We also show that GA has an
      antagonistic effect on root initiation, as the transgenic lines showed poorer
      rooting than the control plants when potted in soil. However, the negative effect
      on rooting efficiencies in the initial establishment of young plantlets in the
      growth chamber did not significantly affect root growth at later stages.

PMID- 10888851
TI  - Seamless gene engineering using RNA- and DNA-overhang cloning.
AB  - Here we describe two methods for generating DNA fragments with single-stranded
      overhangs, like those generated by the activity of many restriction enzymes, by
      simple methods that do not involve DNA digestion. The methods, RNA-overhang
      cloning (ROC) and DNA-overhang cloning (DOC), generate polymerase chain reaction
      (PCR) products composed of double-stranded (ds) DNA flanked by single-stranded
      (ss) RNA or DNA overhangs. The overhangs can be used to recombine DNA fragments
      at any sequence location, creating "perfect" chimeric genes composed of DNA
      fragments that have been joined without the insertion, deletion, or alteration of
      even a single base pair. The ROC method entails using PCR primers that contain
      regions of RNA sequence that cannot be copied by certain thermostable DNA
      polymerases. Using such a chimeric primer in PCR would yield a product with a 5'
      overhang identical to the sequence of the RNA component of the primer, which can
      be used for directional ligation of the amplified product to other preselected
      DNA molecules. This method provides complete control over both the length and
      sequence of the overhangs, and eliminates the need for restriction enzymes as
      tools for gene engineering.

PMID- 10888852
TI  - Enhanced detection and distinction of RNA by enzymatic probe ligation.
AB  - It is important that RNA molecules representing members of gene families are
      distinguished in expression analyses, and even greater resolving power may be
      required to identify allelic variants of transcripts in order to investigate
      imprinting or to study the distribution of mutant genes in tissues. Ligase
      mediated gene detection allows precise distinction of DNA sequence variants, but
      it is not known if ligases can also be used to distinguish variants of RNA
      sequences. Here we present conditions for efficient ligation of pairs of DNA
      oligonucleotides hybridizing next to one another on RNA strands, permitting
      discrimination of any single nucleotide probe-target mismatch by a factor of
      between 20- and 200-fold. The mechanism allows padlock probes to be used to
      distinguish single-nucleotide variants in RNA. Ligase-mediated gene detection
      could therefore provide highly sensitive and accurate ligase-mediated detection
      and distinction of RNA sequence variants in solution, on DNA microarrays, and in
      situ.

PMID- 10888853
TI  - Will publication of patent applications really affect biotechnology?

PMID- 10888854
TI  - Recent patents in high-throughput screening.

PMID- 10888856
TI  - Discovering the original tech stocks.

PMID- 10888855
TI  - Get on the bus.

PMID- 10888859
TI  - A focus on function.

PMID- 10888860
TI  - Restoration of compact discs.

PMID- 10888861
TI  - A look at linkage disequilibrium.

PMID- 10888862
TI  - Meiotic machinations.

PMID- 10888863
TI  - The labyrinthine placenta.

PMID- 10888864
TI  - Touching base

PMID- 10888865
TI  - Eugenics-evolutionary nonsense?

PMID- 10888866
TI  - Hepatocyte migration during liver development requires Prox1.
AB  - Several genes are required during the early phases of liver specification,
      proliferation and differentiation. Here we report that Prox1 is required for
      hepatocyte migration. Loss of Prox1 leads to formation of a smaller liver with a
      reduced population of clustered hepatocytes surrounded by a laminin-rich basal
      membrane.

PMID- 10888867
TI  - Mitochondrial DNA heteroplasmy in cloned cattle produced by fetal and adult cell
      cloning.
AB  - Mammals have been cloned from adult donor cells. Here we report the first cases
      of mitochondrial DNA (mtDNA) heteroplasmy in adult mammalian clones generated
      from fetal and adult donor cells. The heteroplasmic clones included a healthy
      cattle equivalent of the sheep Dolly, for which a lack of heteroplasmy was
      reported.

PMID- 10888868
TI  - ABCR expression in foveal cone photoreceptors and its role in Stargardt macular
      dystrophy.
AB  - Mutations in the gene encoding ABCR are responsible for Stargardt macular
      dystrophy. Here we show by immunofluorescence microscopy and western-blot
      analysis that ABCR is present in foveal and peripheral cone, as well as rod,
      photoreceptors. Our results suggest that the loss in central vision experienced
      by Stargardt patients arises directly from ABCR-mediated foveal cone
      degeneration.

PMID- 10888869
TI  - Genetic testing and quality control in diagnostic laboratories.
AB  - To evaluate the quality of genetic testing for cystic fibrosis, 136, 145 and 159
      laboratories participated in a European study in 1996, 1997 and 1998,
      respectively. We sent six purified DNA samples carrying the more common CFTR
      mutations with the request to test them using routine protocols. A panel of
      experts reviewed the results together with the raw data.

PMID- 10888870
TI  - DNA property rites

PMID- 10888871
TI  - Mitotic replication initiation proteins are not required for pre-meiotic S phase.
AB  - Initiation of mitotic DNA replication in eukaryotes requires conserved factors,
      including Cdc18/CDC6 and minichromosome maintenance (MCM) proteins. We show here
      that these proteins are not essential for meiotic DNA replication or subsequent
      meiotic divisions in fission yeast. In addition, vegetative replication
      checkpoint genes are not required for the arrest of meiotic divisions in response
      to pre-meiotic S-phase delays. Genes essential for other aspects of vegetative
      DNA replication, however, including polymerases and DNA ligase, are also required
      for pre-meiotic DNA synthesis. Our results indicate that the process of
      replication initiation and checkpoint control may be fundamentally different in
      mitotic and meiotic cells.

PMID- 10888872
TI  - DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication
      foci.
AB  - DNA methylation can contribute to transcriptional silencing through several
      transcriptionally repressive complexes, which include methyl-CpG binding domain
      proteins (MBDs) and histone deacetylases (HDACs). We show here that the chief
      enzyme that maintains mammalian DNA methylation, DNMT1, can also establish a
      repressive transcription complex. The non-catalytic amino terminus of DNMT1 binds
      to HDAC2 and a new protein, DMAP1 (for DNMT1 associated protein), and can mediate
      transcriptional repression. DMAP1 has intrinsic transcription repressive
      activity, and binds to the transcriptional co-repressor TSG101. DMAP1 is targeted
      to replication foci through interaction with the far N terminus of DNMT1
      throughout S phase, whereas HDAC2 joins DNMT1 and DMAP1 only during late S phase,
      providing a platform for how histones may become deacetylated in heterochromatin
      following replication. Thus, DNMT1 not only maintains DNA methylation, but also
      may directly target, in a heritable manner, transcriptionally repressive
      chromatin to the genome during DNA replication.

PMID- 10888873
TI  - Mutations in an oocyte-derived growth factor gene (BMP15) cause increased
      ovulation rate and infertility in a dosage-sensitive manner.
AB  - Multiple ovulations are uncommon in humans, cattle and many breeds of sheep.
      Pituitary gonadotrophins and as yet unidentified ovarian factors precisely
      regulate follicular development so that, normally, only one follicle is selected
      to ovulate. The Inverdale (FecXI) sheep, however, carries a naturally occurring X
      linked mutation that causes increased ovulation rate and twin and triplet births
      in heterozygotes (FecXI/FecX+; ref. 1), but primary ovarian failure in
      homozygotes (FecXI/FecXI; ref. 2). Germ-cell development, formation of the
      follicle and the earliest stages of follicular growth are normal in FecXI/FecXI
      sheep, but follicular development beyond the primary stage is impaired. A second
      family unrelated to the Inverdale sheep also has the same X-linked phenotype
      (Hanna, FecXH). Crossing FecXI with FecXH animals produces FecXI/FecXH infertile
      females phenotypically indistinguishable from FecXI/FecXI females. We report here
      that the FecXI locus maps to an orthologous chromosomal region syntenic to human
      Xp11.2-11.4, which contains BMP15, encoding bone morphogenetic protein 15 (also
      known as growth differentiation factor 9B (GDF9B)). Whereas BMP15 is a member of
      the transforming growth factor beta (TGFbeta) superfamily and is specifically
      expressed in oocytes, its function is unknown. We show that independent germline
      point mutations exist in FecXI and FecXH carriers. These findings establish that
      BMP15 is essential for female fertility and that natural mutations in an ovary
      derived factor can cause both increased ovulation rate and infertility phenotypes
      in a dosage-sensitive manner.

PMID- 10888874
TI  - Social amnesia in mice lacking the oxytocin gene.
AB  - The development of social familiarity in rodents depends predominantly on
      olfactory cues and can critically influence reproductive success. Researchers
      have operationally defined this memory by a reliable decrease in olfactory
      investigation in repeated or prolonged encounters with a conspecific. Brain
      oxytocin (OT) and vasopressin (AVP) seem to modulate a range of social behaviour
      from parental care to mate guarding. Pharmacological studies indicate that AVP
      administration may enhance social memory, whereas OT administration may either
      inhibit or facilitate social memory depending on dose, route or paradigm. We
      found that male mice mutant for the oxytocin gene (Oxt-/-) failed to develop
      social memory, whereas wild-type (Oxt+/+) mice showed intact social memory.
      Measurement of both olfactory foraging and olfactory habituation tasks indicated
      that olfactory detection of non-social stimuli is intact in Oxt-/- mice. Spatial
      memory and behavioural inhibition measured in a Morris water-maze, Y-maze, or
      habituation of an acoustic startle also seemed intact. Treatment with OT but not
      AVP rescued social memory in Oxt-/- mice, and treatment with an OT antagonist
      produced a social amnesia-like effect in Oxt+/+ mice. Our data indicate that OT
      is necessary for the normal development of social memory in mice and support the
      hypothesis that social memory has a neural basis distinct from other forms of
      memory.

PMID- 10888875
TI  - Genetic basis of total colourblindness among the Pingelapese islanders.
AB  - Complete achromatopsia is a rare, autosomal recessive disorder characterized by
      photophobia, low visual acuity, nystagmus and a total inability to distinguish
      colours. In this disease, cone photoreceptors, the retinal sensory neurons
      mediating colour vision, seem viable but fail to generate an electrical response
      to light. Achromatopsia, or rod monochromatism, was first mapped to 2p11-2q12
      (MIM 216900; ref. 3), where it is associated with missense mutations in CNGA3
      (ref. 4). CNGA3 encodes the alpha-subunit of the cone cyclic nucleotide-gated
      cation channel, which generates the light-evoked electrical responses of cone
      photoreceptors. A second locus at 8q21-q22 has been identified among the
      Pingelapese islanders of Micronesia, who have a high incidence of recessive
      achromatopsia (MIM 262300). Here we narrow the achromatopsia locus to 1.4 cM and
      show that Pingelapese achromatopsia segregates with a missense mutation at a
      highly conserved site in CNGB3, a new gene that encodes the beta-subunit of the
      cone cyclic nucleotide-gated cation channel. Two independent frameshift deletions
      establish that achromatopsia is the null phenotype of CNGB3. Combined with
      earlier findings, our results demonstrate that both alpha- and beta-subunits of
      the cGMP-gated channel are essential for phototransduction in all three classes
      of cones.

PMID- 10888876
TI  - Gene-expression profile of the ageing brain in mice.
AB  - Ageing of the brain leads to impairments in cognitive and motor skills, and is
      the major risk factor for several common neurological disorders such as Alzheimer
      disease (AD) and Parkinson disease (PD). Recent studies suggest that normal brain
      ageing is associated with subtle morphological and functional alterations in
      specific neuronal circuits, as opposed to large-scale neuronal loss. In fact,
      ageing of the central nervous system in diverse mammalian species shares many
      features, such as atrophy of pyramidal neurons, synaptic atrophy, decrease of
      striatal dopamine receptors, accumulation of fluorescent pigments, cytoskeletal
      abnormalities, and reactive astrocytes and microglia. To provide the first global
      analysis of brain ageing at the molecular level, we used oligonucleotide arrays
      representing 6,347 genes to determine the gene-expression profile of the ageing
      neocortex and cerebellum in mice. Ageing resulted in a gene-expression profile
      indicative of an inflammatory response, oxidative stress and reduced neurotrophic
      support in both brain regions. At the transcriptional level, brain ageing in mice
      displays parallels with human neurodegenerative disorders. Caloric restriction,
      which retards the ageing process in mammals, selectively attenuated the age
      associated induction of genes encoding inflammatory and stress responses.

PMID- 10888877
TI  - Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism.
AB  - Mulibrey nanism (for muscle-liver-brain-eye nanism, MUL; MIM 253250) is an
      autosomal recessive disorder that involves several tissues of mesodermal origin,
      implying a defect in a highly pleiotropic gene. Characteristic features include
      severe growth failure of prenatal onset and constrictive pericardium with
      consequent hepatomegaly. In addition, muscle hypotonia, J-shaped sella turcica,
      yellowish dots in the ocular fundi, typical dysmorphic features and hypoplasia of
      various endocrine glands causing hormonal deficiency are common. About 4% of MUL
      patients develop Wilms' tumour. MUL is enriched in the Finnish population, but is
      rare elsewhere. We previously assigned MUL to chromosome 17q22-q23 and
      constructed a physical contig over the critical MUL region. The region has now
      been further refined by haplotype analysis and new positional candidate genes
      have been localized. We identified a gene with four independent MUL-associated
      mutations that all cause a frameshift and predict a truncated protein. MUL is
      ubiquitously expressed and encodes a new member of the RING-B-box-Coiled-coil
      (RBCC) family of zinc-finger proteins, whose members are involved in diverse
      cellular functions such as developmental patterning and oncogenesis.

PMID- 10888878
TI  - Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase.
AB  - Autosomal recessive juvenile parkinsonism (AR-JP), one of the most common
      familial forms of Parkinson disease, is characterized by selective dopaminergic
      neural cell death and the absence of the Lewy body, a cytoplasmic inclusion body
      consisting of aggregates of abnormally accumulated proteins. We previously cloned
      PARK2, mutations of which cause AR-JP (ref. 2), but the function of the gene
      product, parkin, remains unknown. We report here that parkin is involved in
      protein degradation as a ubiquitin-protein ligase collaborating with the
      ubiquitin-conjugating enzyme UbcH7, and that mutant parkins from AR-JP patients
      show loss of the ubiquitin-protein ligase activity. Our findings indicate that
      accumulation of proteins that have yet to be identified causes a selective neural
      cell death without formation of Lewy bodies. Our findings should enhance the
      exploration of the molecular mechanisms of neurodegeneration in Parkinson disease
      as well as in other neurodegenerative diseases that are characterized by
      involvement of abnormal protein ubiquitination, including Alzheimer disease,
      other tauopathies, CAG triplet repeat disorders and amyotrophic lateral
      sclerosis.

PMID- 10888879
TI  - Restoration of photoreceptor ultrastructure and function in retinal degeneration
      slow mice by gene therapy.
AB  - The gene Prph2 encodes a photoreceptor-specific membrane glycoprotein, peripherin
      2 (also known as peripherin/rds), which is inserted into the rims of
      photoreceptor outer segment discs in a complex with rom-1 (ref. 2). The complex
      is necessary for the stabilization of the discs, which are renewed constantly
      throughout life, and which contain the visual pigments necessary for photon
      capture. Mutations in Prph2 have been shown to result in a variety of
      photoreceptor dystrophies, including autosomal dominant retinitis pigmentosa and
      macular dystrophy. A common feature of these diseases is the loss of
      photoreceptor function, also seen in the retinal degeneration slow (rds or Prph2
      Rd2/Rd2) mouse, which is homozygous for a null mutation in Prph2. It is
      characterized by a complete failure to develop photoreceptor discs and outer
      segments, downregulation of rhodopsin and apoptotic loss of photoreceptor cells.
      The electroretinograms (ERGs) of Prph2Rd2/Rd2 mice have greatly diminished a-wave
      and b-wave amplitudes, which decline to virtually undetectable concentrations by
      two months. Subretinal injection of recombinant adeno-associated virus (AAV)
      encoding a Prph2 transgene results in stable generation of outer segment
      structures and formation of new stacks of discs containing both perpherin-2 and
      rhodopsin, which in many cases are morphologically similar to normal outer
      segments. Moreover, the re-establishment of the structural integrity of the
      photoreceptor layer also results in electrophysiological correction. These
      studies demonstrate for the first time that a complex ultrastructural cell defect
      can be corrected both morphologically and functionally by in vivo gene transfer.

PMID- 10888880
TI  - The glial cells missing-1 protein is essential for branching morphogenesis in the
      chorioallantoic placenta.
AB  - Trophoblast cells of the placenta are established at the blastocyst stage and
      differentiate into specialized subtypes after implantation. In mice, the outer
      layer of the placenta consists of trophoblast giant cells that invade the uterus
      and promote maternal blood flow to the implantation site by producing cytokines
      with angiogenic and vasodilatory actions. The innermost layer, called the
      labyrinth, consists of branched villi that provide a large surface area for
      nutrient transport and are composed of trophoblast cells and underlying
      mesodermal cells derived from the allantois. The chorioallantoic villi develop
      after embryonic day (E) 8.5 through extensive folding and branching of an
      initially flat sheet of trophoblast cells, the chorionic plate, in response to
      contact with the allantois. We show here that Gcm1, encoding the transcription
      factor glial cells missing-1 (Gcm1), is expressed in small clusters of chorionic
      trophoblast cells at the flat chorionic plate stage and at sites of
      chorioallantoic folding and extension when morphogenesis begins. Mutation of Gcm1
      in mice causes a complete block to branching of the chorioallantoic interface,
      resulting in embryonic mortality by E10 due to the absence of the placental
      labyrinth. In addition, chorionic trophoblast cells in Gcm1-deficient placentas
      do not fuse to form syncytiotrophoblast. Abnormal development of placental villi
      is frequently associated with fetal death and intrauterine growth restriction in
      humans, and our studies provide the earliest molecular insight into this aspect
      of placental development.

PMID- 10888881
TI  - Epigenetic inactivation of a RAS association domain family protein from the lung
      tumour suppressor locus 3p21.3.
AB  - Allelic loss at the short arm of chromosome 3 is one of the most common and
      earliest events in the pathogenesis of lung cancer, and is observed in more than
      90% of small-cell lung cancers (SCLCs) and in 50-80% of non-small-cell lung
      cancers (NSCLCs). Frequent and early loss of heterozygosity and the presence of
      homozygous deletions suggested a critical role of the region 3p21.3 in
      tumorigenesis and a region of common homozygous deletion in 3p21.3 was narrowed
      to 120 kb (ref. 5). Several putative tumour-suppressor genes located at 3p21 have
      been characterized, but none of these genes appear to be altered in lung cancer.
      Here we describe the cloning and characterization of a human RAS effector
      homologue (RASSF1) located in the 120-kb region of minimal homozygous deletion.
      We identified three transcripts, A, B and C, derived from alternative splicing
      and promoter usage. The major transcripts A and C were expressed in all normal
      tissues. Transcript A was missing in all SCLC cell lines analysed and in several
      other cancer cell lines. Loss of expression was correlated with methylation of
      the CpG-island promoter sequence of RASSF1A. The promoter was highly methylated
      in 24 of 60 (40%) primary lung tumours, and 4 of 41 tumours analysed carried
      missense mutations. Re-expression of transcript A in lung carcinoma cells reduced
      colony formation, suppressed anchorage-independent growth and inhibited tumour
      formation in nude mice. These characteristics indicate a potential role for
      RASSF1A as a lung tumour suppressor gene.

PMID- 10888882
TI  - The genetically isolated populations of Finland and sardinia may not be a panacea
      for linkage disequilibrium mapping of common disease genes.
AB  - The choice of which population to study in the mapping of common disease genes
      may be critical. Isolated founder populations, such as that found in Finland,
      have already proved extremely useful for mapping the genes for specific rare
      monogenic disorders and are being used in attempts to map the genes underlying
      common, complex diseases. But simulation results suggest that, under the common
      disease-common variant hypothesis, most isolated populations will prove no more
      useful for linkage disequilibrium (LD) mapping of common disease genes than large
      outbred populations. There is very little empirical data to either support or
      refute this conclusion at present. Therefore, we evaluated LD between 21 common
      microsatellite polymorphisms on chromosome 18q21 in 2 genetic isolates (Finland
      and Sardinia) and compared the results with those observed in two mixed
      populations (United Kingdom and United States of America). Mean levels of LD were
      similar across all four populations. Our results provide empirical support for
      the expectation that genetic isolates like Finland and Sardinia will not prove
      significantly more valuable than general populations for LD mapping of common
      variants underlying complex disease.

PMID- 10888883
TI  - Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25
      and Xq28.
AB  - Linkage disequilibrium (LD), or the non-random association of alleles, is poorly
      understood in the human genome. Population genetic theory suggests that LD is
      determined by the age of the markers, population history, recombination rate,
      selection and genetic drift. Despite the uncertainties in determining the
      relative contributions of these factors, some groups have argued that LD is a
      simple function of distance between markers. Disease-gene mapping studies and a
      simulation study gave differing predictions on the degree of LD in isolated and
      general populations. In view of the discrepancies between theory and experimental
      observations, we constructed a high-density SNP map of the Xq25-Xq28 region and
      analysed the male genotypes and haplotypes across this region for LD in three
      populations. The populations included an outbred European sample (CEPH males) and
      isolated population samples from Finland and Sardinia. We found two extended
      regions of strong LD bracketed by regions with no evidence for LD in all three
      samples. Haplotype analysis showed a paucity of haplotypes in regions of strong
      LD. Our results suggest that, in this region of the X chromosome, LD is not a
      monotonic function of the distance between markers, but is more a property of the
      particular location in the human genome.

PMID- 10888884
TI  - Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice.
AB  - Syndecan-1 is a cell-surface, heparan-sulphate proteoglycan (HSPG) predominantly
      expressed by epithelial cells. It binds specifically to many proteins, including
      oncoproteins. For example, it induces the assembly of a signalling complex
      between FGF ligands and their cognate receptors. But so far there has been no
      direct evidence that this proteoglycan contributes to tumorigenesis. Here we have
      examined the role of syndecan-1 (encoded by Sdc1) during mammary tumour formation
      in response to the ectopic expression of the proto-oncogene Wnt1. We crossed
      syndecan-1-deficient mice with transgenic mice that express Wnt1 in mammary gland
      (TgN(Wnt-1)1Hev; ref. 2). Ectopic Wnt-1 expression induces generalized mammary
      hyperplasia, followed by the development of solitary tumours (median time 22
      weeks). We show that in Sdc1-/- mice, Wnt-1-induced hyperplasia in virgin mammary
      gland was reduced by 70%, indicating that the Wnt-1 signalling pathway was
      inhibited. Of the 39 tumours that developed in a test cohort of mice, only 1
      evolved in the Sdc1-/- background. In addition, we show that soluble syndecan-1
      ectodomain purified from mouse mammary epithelial cells stimulates the activity
      of a Wnt-1 homologue in a tissue culture assay. Our results provide both genetic
      and biochemical evidence that syndecan-1 can modulate Wnt signalling, and is
      critical for Wnt-1-induced tumorigenesis of the mouse mammary gland.

PMID- 10888885
TI  - Widespread aneuploidy revealed by DNA microarray expression profiling.
AB  - Expression profiling using DNA microarrays holds great promise for a variety of
      research applications, including the systematic characterization of genes
      discovered by sequencing projects. To demonstrate the general usefulness of this
      approach, we recently obtained expression profiles for nearly 300 Saccharomyces
      cerevisiae deletion mutants. Approximately 8% of the mutants profiled exhibited
      chromosome-wide expression biases, leading to spurious correlations among
      profiles. Competitive hybridization of genomic DNA from the mutant strains and
      their isogenic parental wild-type strains showed they were aneuploid for whole
      chromosomes or chromosomal segments. Expression profile data published by several
      other laboratories also suggest the use of aneuploid strains. In five separate
      cases, the extra chromosome harboured a close homologue of the deleted gene; in
      two cases, a clear growth advantage for cells acquiring the extra chromosome was
      demonstrated. Our results have implications for interpreting whole-genome
      expression data, particularly from cells known to suffer genomic instability,
      such as malignant or immortalized cells.

PMID- 10888886
TI  - DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from
      E2F-responsive promoters.
AB  - Methylation of CpG islands is associated with transcriptional silencing and the
      formation of nuclease-resistant chromatin structures enriched in hypoacetylated
      histones. Methyl-CpG-binding proteins, such as MeCP2, provide a link between
      methylated DNA and hypoacetylated histones by recruiting histone deacetylase, but
      the mechanisms establishing the methylation patterns themselves are unknown.
      Whether DNA methylation is always causal for the assembly of repressive chromatin
      or whether features of transcriptionally silent chromatin might target
      methyltransferase remains unresolved. Mammalian DNA methyltransferases show
      little sequence specificity in vitro, yet methylation can be targeted in vivo
      within chromosomes to repetitive elements, centromeres and imprinted loci. This
      targeting is frequently disrupted in tumour cells, resulting in the improper
      silencing of tumour-suppressor genes associated with CpG islands. Here we show
      that the predominant mammalian DNA methyltransferase, DNMT1, co-purifies with the
      retinoblastoma (Rb) tumour suppressor gene product, E2F1, and HDAC1 and that
      DNMT1 cooperates with Rb to repress transcription from promoters containing E2F
      binding sites. These results establish a link between DNA methylation, histone
      deacetylase and sequence-specific DNA binding activity, as well as a growth
      regulatory pathway that is disrupted in nearly all cancer cells.

PMID- 10888887
TI  - Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a
      subset of human autosomal recessive osteopetrosis.
AB  - Osteopetrosis includes a group of inherited diseases in which inadequate bone
      resorption is caused by osteoclast dysfunction. Although molecular defects have
      been described for many animal models of osteopetrosis, the gene responsible for
      most cases of the severe human form of the disease (infantile malignant
      osteopetrosis) is unknown. Infantile malignant autosomal recessive osteopetrosis
      (MIM 259700) is a severe bone disease with a fatal outcome, generally within the
      first decade of life. Osteoclasts are present in normal or elevated numbers in
      individuals affected by autosomal recessive osteopetrosis, suggesting that the
      defect is not in osteoclast differentiation, but in a gene involved in the
      functional capacity of mature osteoclasts. Some of the mouse mutants have a
      decreased number of osteoclasts, which suggests that the defect directly
      interferes with osteoclast differentiation. In other mutants, it is the function
      of the osteoclast that seems to be affected, as they show normal or elevated
      numbers of non-functioning osteoclasts. Here we show that TCIRG1, encoding the
      osteoclast-specific 116-kD subunit of the vacuolar proton pump, is mutated in
      five of nine patients with a diagnosis of infantile malignant osteopetrosis. Our
      data indicate that mutations in TCIRG1 are a frequent cause of autosomal
      recessive osteopetrosis in humans.

PMID- 10888888
TI  - Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human
      telomeres.
AB  - Telomeres allow cells to distinguish natural chromosome ends from damaged DNA and
      protect the ends from degradation and fusion. In human cells, telomere protection
      depends on the TTAGGG repeat binding factor, TRF2 (refs 1-4), which has been
      proposed to remodel telomeres into large duplex loops (t-loops). Here we show by
      nanoelectrospray tandem mass spectrometry that RAD50 protein is present in TRF2
      immunocomplexes. Protein blotting showed that a small fraction of RAD50, MRE11
      and the third component of the MRE11 double-strand break (DSB) repair complex,
      the Nijmegen breakage syndrome protein (NBS1), is associated with TRF2. Indirect
      immunofluorescence demonstrated the presence of RAD50 and MRE11 at interphase
      telomeres. NBS1 was associated with TRF2 and telomeres in S phase, but not in G1
      or G2. Although the MRE11 complex accumulated in irradiation-induced foci (IRIFs)
      in response to gamma-irradiation, TRF2 did not relocate to IRIFs and irradiation
      did not affect the association of TRF2 with the MRE11 complex, arguing against a
      role for TRF2 in DSB repair. Instead, we propose that the MRE11 complex functions
      at telomeres, possibly by modulating t-loop formation.

PMID- 10888889
TI  - A syndrome of tricuspid atresia in mice with a targeted mutation of the gene
      encoding Fog-2.
AB  - Tricuspid atresia (TA) is a common form of congenital heart disease, accounting
      for 1-3% of congenital cardiac disorders. TA is characterized by the congenital
      agenesis of the tricuspid valve connecting the right atrium to the right
      ventricle and both an atrial septal defect (ASD) and a ventricular septal defect
      (VSD). Some patients also have pulmonic stenosis, persistence of a left-sided
      superior vena cava or transposition of the great arteries. Most cases of TA are
      sporadic, but familial occurrences with disease in multiple siblings have been
      reported. Gata4 is a zinc-finger transcription factor with a role in early
      cardiac development. Gata4-deficient mice fail to form a ventral heart tube and
      die of circulatory failure at embryonic day (E) 8.5 (refs 6,7). Zfpm2 (also known
      as Fog-2) is a multi-zinc-finger protein that is co-expressed with Gata4 in the
      developing heart beginning at E8.5 (refs 8-10). Zfpm2 interacts specifically with
      the N-terminal zinc finger of Gata4 and represses Gata4-dependent transcription.
      Here we use targeted mutagenesis to explore the role of Zfpm2 in normal cardiac
      development. Zfpm2-deficient mice died of congestive heart failure at E13 with a
      syndrome of tricuspid atresia that includes an absent tricuspid valve, a large
      ASD, a VSD, an elongated left ventricular outflow tract, rightward displacement
      of the aortic valve and pulmonic stenosis. These mice also display hypoplasia of
      the compact zone of the left ventricle. Our findings indicate the importance of
      Zfpm2 in the normal looping and septation of the heart and suggest a genetic
      basis for the syndrome of tricuspid atresia.

PMID- 10888890
TI  - Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with
      bone cysts.
AB  - Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy
      (PLOSL; MIM 221770), also known as Nasu-Hakola disease, is a recessively
      inherited disease characterized by a combination of psychotic symptoms rapidly
      progressing to presenile dementia and bone cysts restricted to wrists and ankles.
      PLOSL has a global distribution, although most of the patients have been
      diagnosed in Finland and Japan, with an estimated population prevalence of 2x10-6
      (ref. 2) in the Finns. We have previously identified a shared 153-kb ancestor
      haplotype in all Finnish disease alleles between markers D19S1175 and D19S608 on
      chromosome 19q13.1 (refs 5,6). Here we characterize the molecular defect in PLOSL
      by identifying one large deletion in all Finnish PLOSL alleles and another
      mutation in a Japanese patient, both representing loss-of-function mutations, in
      the gene encoding TYRO protein tyrosine kinase binding protein (TYROBP; formerly
      DAP12). TYROBP is a transmembrane protein that has been recognized as a key
      activating signal transduction element in natural killer (NK) cells. On the
      plasma membrane of NK cells, TYROBP associates with activating receptors
      recognizing major histocompatibility complex (MHC) class I molecules. No
      abnormalities in NK cell function were detected in PLOSL patients homozygous for
      a null allele of TYROBP.

PMID- 10888891
TI  - Gene therapy: cautious optimism.

PMID- 10888892
TI  - Clearance of amyloid beta-peptide from brain: transport or metabolism?

PMID- 10888893
TI  - Clearance of amyloid beta-peptide from brain: transport or metabolism?

PMID- 10888894
TI  - Temporary inactivation of follicular dendritic cells delays neuroinvasion of
      scrapie.

PMID- 10888895
TI  - Special focus on malaria

PMID- 10888896
TI  - For sale: The Framingham Heart Study.

PMID- 10888897
TI  - US gene therapists rally at annual meeting.

PMID- 10888898
TI  - New data show life is longer, better, but more expensive.

PMID- 10888899
TI  - Industry outlines its perspective on new third-world vaccine development.

PMID- 10888900
TI  - Angiogenesis team sued by pharmaceutical company.

PMID- 10888901
TI  - Troubled academic medical school escapes censure.

PMID- 10888902
TI  - Ogilvie warns australia to heed UK university demise.

PMID- 10888903
TI  - UK MRC neglects researchers.

PMID- 10888904
TI  - JDF expands research effort.

PMID- 10888905
TI  - Beanie Baby profits support AIDS foundation.

PMID- 10888906
TI  - South Africa signs MoU with US.

PMID- 10888907
TI  - WHO under attack on HIV drug policy.

PMID- 10888908
TI  - Seymour S. Kety 1915-2000

PMID- 10888910
TI  - Stress, coping, and depression

PMID- 10888909
TI  - Balancing risks on the backs of the poor.

PMID- 10888911
TI  - Taking aim at HIV replication.

PMID- 10888912
TI  - HIV-1 rebound after anti-retroviral therapy.

PMID- 10888913
TI  - Do 'demyelinating' diseases involve more than myelin?

PMID- 10888914
TI  - Activin to the rescue for overexcited neurons.

PMID- 10888915
TI  - Dangerous signals from E. coli toxin.

PMID- 10888916
TI  - Transcriptional regulation of cellular transformation.

PMID- 10888917
TI  - Measles vaccines--a positive step toward eradicating a negative strand.

PMID- 10888918
TI  - The vision of typhoon lengkieki.

PMID- 10888919
TI  - Mammalian deconstruction for stem cell reconstruction.

PMID- 10888920
TI  - Dengue virus and dendritic cells.

PMID- 10888921
TI  - Research news

PMID- 10888922
TI  - Transmissible spongiform encephalopathies, amyloidoses and yeast prions: common
      threads?

PMID- 10888923
TI  - Relationship between pre-existing viral reservoirs and the re-emergence of plasma
      viremia after discontinuation of highly active anti-retroviral therapy.
AB  - We examined the pathogenic significance of the latent viral reservoir in the
      resting CD4+ T cell compartment of HIV-1-infected individuals as well as its
      involvement in the rebound of plasma viremia after discontinuation of highly
      active anti-retroviral therapy (HAART). Using heteroduplex mobility and tracking
      assays, we show that the detectable pool of latently infected, resting CD4+ T
      cells does not account entirely for the early rebounding plasma HIV in infected
      individuals in whom HAART has been discontinued. In the majority of patients
      examined, the rebounding plasma virus was genetically distinct from both the cell
      associated HIV RNA and the replication-competent virus within the detectable pool
      of latently infected, resting CD4 + T cells. These results indicate the existence
      of other persistent HIV reservoirs that could prompt rapid emergence of plasma
      viremia after cessation of HAART and underscore the necessity to develop
      therapies directed toward such populations of infected cells.

PMID- 10888924
TI  - Effects of mycophenolic acid on human immunodeficiency virus infection in vitro
      and in vivo.
AB  - Mycophenolic acid, a selective inhibitor of the de novo synthesis of guanosine
      nucleotides in T and B lymphocytes, has been proposed to inhibit human
      immunodeficiency virus (HIV) replication in vitro by depleting the substrate
      (guanosine nucleotides) for reverse transcriptase. Here we show that mycophenolic
      acid induced apoptosis and cell death in a large proportion of activated CD4+ T
      cells, thus indicating that it may inhibit HIV infection in vitro by both
      virological mechanisms and immunological mechanisms (depletion of the pool of
      activated CD4+ T lymphocytes). Administration of mycophenolate mophetil, the
      ester derivate of mycophenolic acid, to HIV-infected subjects treated with anti
      retroviral therapy and with undetectable viremia resulted in the reduction of the
      number of dividing CD4 + and CD8+ T cells and in the inhibition of virus
      isolation from purified CD4+ T-cell populations. Based on these results, the
      potential use of mycophenolate mophetil in the treatment of HIV infection
      deserves further investigation in controlled clinical trials.

PMID- 10888925
TI  - Transfer of the chemokine receptor CCR5 between cells by membrane-derived
      microparticles: a mechanism for cellular human immunodeficiency virus 1
      infection.
AB  - The release of microparticles from eukaryotic cells is a well-recognized
      phenomenon. We demonstrate here that the chemokine receptor CCR5, the principal
      co-receptor for macrophage-tropic human immunodeficiency virus (HIV)-1, can be
      released through microparticles from the surface of CCR5+ Chinese hamster ovary
      cells and peripheral blood mononuclear cells. Microparticles containing CCR5 can
      transfer the receptor to CCR5- cells and render them CCR5+. The CCR5 transfer to
      CCR5-deficient peripheral blood mononuclear cells homozygous for a 32-base-pair
      deletion in the CCR5 gene enabled infection of these cells with macrophage-tropic
      HIV-1. In monocytes, the transfer of CCR5 could be inhibited by cytochalasin D,
      and transferred CCR5 could be downmodulated by chemokines. A transfer of CCR5
      from peripheral blood mononuclear cells to endothelial cells during
      transendothelial migration could be demonstrated. Thus, the transfer of CCR5 may
      lead to infection of tissues without endogenous CCR5 expression. Moreover, the
      intercellular transfer of membrane proteins by microparticles might have broader
      consequences for intercellular communication beyond the effects seen for HIV-1.

PMID- 10888926
TI  - Successful DNA immunization against measles: neutralizing antibody against either
      the hemagglutinin or fusion glycoprotein protects rhesus macaques without
      evidence of atypical measles.
AB  - Measles remains a principal cause of worldwide mortality, in part because young
      infants cannot be immunized effectively. Development of new vaccines has been
      hindered by previous experience with a formalin-inactivated vaccine that
      predisposed to a severe form of disease (atypical measles). Here we have
      developed and tested potential DNA vaccines for immunogenicity, efficacy and
      safety in a rhesus macaque model of measles. DNA protected from challenge with
      wild-type measles virus. Protection correlated with levels of neutralizing
      antibody and not with cytotoxic T lymphocyte activity. There was no evidence in
      any group, including those receiving hemagglutinin-encoding DNA alone, of
      'priming' for atypical measles.

PMID- 10888927
TI  - Identification of a previously unknown antigen-specific regulatory T cell and its
      mechanism of suppression.
AB  - Despite increasing evidence for the existence of antigen-specific regulatory T
      cells, the mechanisms underlying suppression remain unclear. In this study we
      have identified and cloned a novel subset of antigen-specific regulatory T cells
      and demonstrated that these T cells possess a unique combination of cell surface
      markers and array of cytokines. The regulatory T cells are able to inhibit the
      function of T cells carrying the same T-cell receptor specificity and prevent
      skin allograft rejection in an antigen-specific, dose-dependent manner. The
      regulatory T cells are able to acquire alloantigen from antigen-presenting cells,
      present the alloantigen to activated syngeneic CD8+ T cells and then send death
      signals to CD8+ T cells. These findings provide a novel mechanism of regulatory T
      cell-mediated, antigen-specific suppression.

PMID- 10888928
TI  - Fas/FADD-mediated activation of a specific program of inflammatory gene
      expression in vascular smooth muscle cells.
AB  - Apoptosis of smooth muscle cells is a common feature of vascular lesions but its
      pathophysiological significance is not known. We demonstrate that signals
      initiated by regulated Fas-associated death domain protein overexpression in rat
      vascular smooth muscle cells in the carotid artery induce expression of monocyte
      chemoattractant protein-1 and interleukin-8, and cause massive immigration of
      macrophages in vivo. These chemokines, and a specific set of other pro
      inflammatory genes, are also upregulated in human vascular smooth muscle cells
      during Fas-induced apoptosis, in part through a process that requires interleukin
      1alpha activation. Induction of a pro-inflammatory program by apoptotic vascular
      smooth muscle cells may thus contribute to the pathogenesis of vascular disease.

PMID- 10888929
TI  - Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a
      transgenic mouse model of Huntington disease.
AB  - Huntington disease is an autosomal dominant neurodegenerative disease with no
      effective treatment. Minocycline is a tetracycline derivative with proven safety.
      After ischemia, minocycline inhibits caspase-1 and inducible nitric oxide
      synthetase upregulation, and reduces infarction. As caspase-1 and nitric oxide
      seem to play a role in Huntington disease, we evaluated the therapeutic efficacy
      of minocycline in the R6/2 mouse model of Huntington disease. We report that
      minocycline delays disease progression, inhibits caspase-1 and caspase-3 mRNA
      upregulation, and decreases inducible nitric oxide synthetase activity. In
      addition, effective pharmacotherapy in R6/2 mice requires caspase-1 and caspase-3
      inhibition. This is the first demonstration of caspase-1 and caspase-3
      transcriptional regulation in a Huntington disease model.

PMID- 10888930
TI  - The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter
      involved in the regulation of food intake.
AB  - The dorsomedial hypothalamic nucleus harbors leptin sensitive neurons and is
      intrinsically connected to hypothalamic nuclei involved in feeding behavior.
      However, it also receives ascending input from the visceroceptive neurons of the
      brainstem. We have identified a unique glucagon-like-peptide-2 containing
      neuronal pathway connecting the nucleus of the solitary tract with the
      dorsomedial hypothalamic nucleus. A glucagon-like-peptide-2 fiber plexus targets
      neurons expressing its receptor within the dorsomedial hypothalamic nucleus.
      Pharmacological and behavioral studies confirmed that glucagon-like-peptide-2
      signaling is a specific transmitter inhibiting rodent feeding behavior and with
      potential long-term effects on body weight homeostasis. The glucagon-like-peptide
      1 receptor antagonist, Exendin (9-39) is also a functional antagonist of
      centrally applied glucagon-like-peptide-2.

PMID- 10888931
TI  - An endogenous pentapeptide acting as a sodium channel blocker in inflammatory
      autoimmune disorders of the central nervous system.
AB  - Reversible blockade of sodium channels by endogenous substances has been claimed
      to account for the fast exacerbations and relapses commonly seen in demyelinating
      autoimmune diseases. Evidence has been provided that in the cerebrospinal fluid
      of patients with multiple sclerosis or Guillain-Barre syndrome, a sodium-channel
      blocking factor exists that has properties of local anesthetic agents. This
      factor could contribute to the nerve conduction block and paresis seen in these
      disorders. We describe here a previously unknown endogenous substance in human
      cerebrospinal fluid with distinct channel-blocking properties even at very low
      (0.00001 M) concentrations. The pentapeptide with the sequence Gln-Tyr-Asn-Ala
      Asp exerted its blocking action by shifting the steady-state inactivation curve
      of the sodium channels to more-negative potentials, as most local anesthetics do.
      In the cerebrospinal fluid of healthy individuals, its concentration was about 3
      microM, whereas in patients with multiple sclerosis and Guillain-Barre syndrome,
      it increased 300-1,400%. At these concentrations, the peptide's blocking efficacy
      was higher than that of 50 microM lidocaine. At a concentration of 10 microM,
      lidocaine is able to 'unmask' subclinical lesions in multiple sclerosis; thus,
      the endogenous pentapeptide may well contribute to the fast changes of symptoms.
      Furthermore, it may become valuable as a marker of disease activity.

PMID- 10888932
TI  - Induction of activin A is essential for the neuroprotective action of basic
      fibroblast growth factor in vivo.
AB  - Exogenous application of neurotrophic growth factors has emerged as a new and
      particularly promising approach not only to promote functional recovery after
      acute brain injury but also to protect neurons against the immediate effect of
      the injury. Among the various growth factors and cytokines studied so far, the
      neuroprotective and neurotrophic profile of basic fibroblast growth factor (bFGF)
      is the best documented. Using an animal model of acute excitotoxic brain injury,
      we report here that the neuroprotective action of bFGF, which is now being tested
      in stroke patients, depends on the induction of activin A, a member of the
      transforming growth factor-beta superfamily. Our evidence for this previously
      unknown mechanism of action of bFGF is that bFGF strongly enhanced lesion
      associated induction of activin A; in the presence of the activin-neutralizing
      protein follistatin, bFGF was no longer capable of rescuing neurons from
      excitotoxic death; and recombinant activin A exerted a neuroprotective effect by
      itself. Our data indicate that the development of substances influencing activin
      expression or receptor binding should offer new ways to fight neuronal loss in
      ischemic and traumatic brain injury.

PMID- 10888933
TI  - Human skin Langerhans cells are targets of dengue virus infection.
AB  - Dengue virus (DV), an arthropod-borne flavivirus, causes a febrile illness for
      which there is no antiviral treatment and no vaccine. Macrophages are important
      in dengue pathogenesis; however, the initial target cell for DV infection remains
      unknown. As DV is introduced into human skin by mosquitoes of the genus Aedes, we
      undertook experiments to determine whether human dendritic cells (DCs) were
      permissive for the growth of DV. Initial experiments demonstrated that blood
      derived DCs were 10-fold more permissive for DV infection than were monocytes or
      macrophages. We confirmed this with human skin DCs (Langerhans cells and
      dermal/interstitial DCs). Using cadaveric human skin explants, we exposed skin
      DCs to DV ex vivo. Of the human leukocyte antigen DR-positive DCs that migrated
      from the skin, emigrants from both dermis and epidermis, 60-80% expressed DV
      antigens. These observations were supported by histologic findings from the skin
      rash of a human subject who received an attenuated tetravalent dengue vaccine.
      Immunohistochemistry of the skin showed CD1a-positive DCs double-labeled with an
      antibody against DV envelope glycoprotein. These data demonstrate that human skin
      DCs are permissive for DV infection, and provide a potential mechanism for the
      transmission of DV into human skin.

PMID- 10888934
TI  - Exploiting tumor-specific defects in the interferon pathway with a previously
      unknown oncolytic virus.
AB  - Interferons are circulating factors that bind to cell surface receptors,
      activating a signaling cascade, ultimately leading to both an antiviral response
      and an induction of growth inhibitory and/or apoptotic signals in normal and
      tumor cells. Attempts to exploit the ability of interferons to limit the growth
      of tumors in patients has met with limited results because of cancer-specific
      mutations of gene products in the interferon pathway. Although interferon-non
      responsive cancer cells may have acquired a growth/survival advantage over their
      normal counterparts, they may have simultaneously compromised their antiviral
      response. To test this, we used vesicular stomatitis virus (VSV), an enveloped,
      negative-sense RNA virus exquisitely sensitive to treatment with interferon. VSV
      rapidly replicated in and selectively killed a variety of human tumor cell lines
      even in the presence of doses of interferon that completely protected normal
      human primary cell cultures. A single intratumoral injection of VSV was effective
      in reducing the tumor burden of nude mice bearing subcutaneous human melanoma
      xenografts. Our results support the use of VSV as a replication-competent
      oncolytic virus and demonstrate a new strategy for the treatment of interferon
      non-responsive tumors.

PMID- 10888935
TI  - The neuronal repressor REST/NRSF is an essential regulator in medulloblastoma
      cells.
AB  - Medulloblastoma is the most malignant pediatric brain tumor. It is believed to
      originate from the undifferentiated external granule layer cells in the
      cerebellum, but the mechanism of tumorigenesis remains unknown. Here we studied
      three types of human medulloblastoma cells that express markers corresponding to
      different levels of neuronal differentiation. They expressed the neuronal
      repressor element 1 (RE1) silencing transcription factor/neuron-restrictive
      silencer factor (REST/NRSF; refs. 7-10) at very high levels compared with either
      neuronal progenitor NTera2 (NT2) cells or fully differentiated human neuron
      teratocarcinoma (hNT cells). To counter the effect of REST/NRSF, we used a
      recombinant transcription factor, REST-VP16, constructed by replacing repressor
      domains of REST/NRSF with the activation domain of viral protein (VP16).
      Transient expression of REST-VP16 in medulloblastoma cells was able to compete
      with the endogenous REST/NRSF for DNA binding and stimulate neuronal promoters.
      High-efficiency expression of REST-VP16 mediated by adenovirus vectors (Ad.REST
      VP16) in medulloblastoma cells was able to counter REST/NRSF-mediated repression
      of neuronal promoters, stimulate expression of endogenous neuronal genes and
      trigger apoptosis through the activation of caspase cascades. Furthermore,
      intratumoral injection of Ad.REST-VP16 in established medulloblastoma tumors in
      nude mice inhibited their growth. Therefore, REST/NRSF may serve as a new target
      for therapeutic interventions for medulloblastoma through agents such as REST
      VP16.

PMID- 10888937
TI  - On the market

PMID- 10888936
TI  - Flow cytometry counting of CD34+ cells in whole blood.

PMID- 10888938
TI  - Correction

PMID- 10888940
TI  - Results of a longer than 10-year follow-Up of patients with rheumatoid arthritis
      treated by occipitocervical fusion.
AB  - STUDY DESIGN: Evaluation of results a longer than 10-year follow-up of patients
      with upper cervical lesions due to rheumatoid arthritis who underwent
      occipitocervical fusion. OBJECTIVE: To determine the final outcome of patients
      with upper cervical lesions due to rheumatoid arthritis treated by
      occipitocervical fusion. SUMMARY OF BACKGROUND DATA: There are few studies
      reporting the final outcome of patients with rheumatoid arthritis treated by
      occipitocervical fusion and observed for longer than 10 years. METHODS: The
      subjects were 16 patients with rheumatoid arthritis with myelopathy who underwent
      occipitocervical fusion with a rectangular rod more than 10 years ago. All 16
      patients had irreducible atlantoaxial dislocation, and 11 also had vertical
      dislocation of the axis. All patients had preoperative nuchal pain, and were
      classified into Class II (two patients), Class IIIA (nine patients), and class
      IIIB (five patients) according to Ranawat's preoperative neurologic
      classification. RESULTS: The atlas-dens interval remained the same as immediately
      after surgery. Vertical dislocation returned to the preoperative condition,
      despite successful surgical correction. Preoperative occipital pain disappeared
      or was reduced in all cases. Myelopathy improved in 12 of the 16 patients (75%)
      by more than one class in the Ranawat preoperative neurologic classification.
      Survival rate at 10 years after surgery was 38%; mean age at death was 70.7
      years. The postoperative periods during which patients could walk by themselves
      ranged from 6 months to 13 years (mean, 7.5 years). CONCLUSIONS: Occipitocervical
      fusion for patients with rheumatoid arthritis is useful for decreasing nuchal
      pain, reducing myelopathy, and improving prognosis.

PMID- 10888941
TI  - Minimum 10-year outcome of decompressive laminectomy for degenerative lumbar
      spinal stenosis.
AB  - STUDY DESIGN: A retrospective follow-up study was conducted in patients who
      underwent decompressive laminectomy for degenerative lumbar spinal stenosis.
      OBJECTIVES: To describe the long-term outcome of decompressive laminectomy
      performed for degenerative lumbar spinal stenosis, and to investigate
      preoperative factors that influenced outcomes, especially risk factors
      predisposing patients to poor results. SUMMARY OF BACKGROUND DATA: The success
      rate of surgical treatment of decompressive laminectomy for lumbar spinal
      stenosis varies. Long-term follow-up investigations have indicated deterioration
      of outcome; however, the causes of deterioration have not been fully
      investigated, and there have been no reports with a minimum 10-year follow-up.
      METHODS: Of 151 patients who underwent decompressive laminectomy from 1980
      through 1989, 37 were followed up for a minimum of 10 years. The mean age at
      surgery was 60.9 +/- 8. 2 years (range, 43-76), and the average follow-up period
      was 13.1 +/- 2.1 years (range, 10.1-17.4). The results were evaluated by the
      criteria of the Japanese Orthopedic Association Lumbar Score, and the outcome was
      classified as excellent at more than 75% improved score; good, 50-75%; fair, 25
      49%; and poor, 0-24% or less. Information about impairment of activities of daily
      living was also obtained at follow-up. Associations between preoperative clinical
      and radiographic variables and clinical outcome were evaluated statistically.
      RESULTS: In all patients, the average score improvement of 55.2 +/- 31.6% was
      regarded as acceptable. The postoperative score and percentage of improvement of
      low back pain were lower than those of leg pain and walking ability. No
      impairment in activities of daily living was found in 62.2% of the patients. Rate
      of improvement was evaluated as excellent in 13 (35.1%), good in 8 (21.6%), fair
      in 8, and poor in 8 patients. Three patients required additional surgery because
      of disc herniation at the laminectomied segments. The patients with multiple
      laminectomy (P = 0.034) and more than 10 degrees preoperative sagittal rotation
      angle (P = 0.018) showed a significantly poorer outcome than the remainder of the
      patients. CONCLUSIONS: Long-term follow-up showed that even without spinal
      fusion, more than half the patients were evaluated as excellent or good. Patients
      with more than a 10 degrees sagittalrotation angle who need multiple laminectomy,
      should be given information about the possibility of earlier deterioration of the
      outcome, and alternative or additional treatment such as concomitant spinal
      fusion with decompression may be considered.

PMID- 10888942
TI  - Accuracy of atlantoaxial transarticular screw insertion.
AB  - STUDY DESIGN: The accuracy and safety of atlantoaxial transarticular screw
      insertion were evaluated in clinical cases. OBJECTIVES: To evaluate the accuracy
      and safety of atlantoaxial transarticular screw insertion under lateral
      fluoroscopic monitoring without opening the joint. SUMMARY OF BACKGROUND DATA:
      Atlantoaxial transarticular screw fixation has been reported to be
      biomechanically superior to posterior atlantoaxial wiring techniques. Several
      clinical series have been reported in the literature. In some reports, the risk
      of screw insertion in this technique has been pointed out. MATERIALS AND METHODS:
      Fifty-six consecutive patients with atlantoaxial instability were treated by
      transarticular screw fixation. One hundred twelve screw insertions in these 56
      patients were assessed by surgical record and computed tomographic examination.
      One screw could not be inserted because of the difficulty of adequate placement
      during operation; 111 screws were therefore inserted. Adequate position was
      defined as when the screw perforated the lateral atlantoaxial joint. RESULTS: In
      this series, neither vertebral artery injury nor spinal cord injury was
      experienced clinically. One guide wire was broken during drilling with a
      cannulated drill. Computed tomographic examination demonstrated that 106 screws
      perforated the atlantoaxial joint. Therefore, 95.5% of screws were adequately
      positioned. There were two screws positioned lateral to the joint, two medially,
      and one anteroinferiorly to the joint. CONCLUSIONS: Atlantoaxial transarticular
      screw insertion using image intensifier without opening the lateral joint was
      performed safely, but not accurately, in all cases.

PMID- 10888943
TI  - Selective developmental regulation of gene expression for insulin-like growth
      factor-binding proteins in mouse spinal cord.
AB  - STUDY DESIGN: Prospective, randomized experimental study in mice. STUDY
      OBJECTIVE: To determine whether insulin-like growth factor binding proteins
      (IGFBPs) are present in mouse spinal cord and, if so, what role they play in its
      development. SUMMARY OF BACKGROUND DATA: Insulin-like growth factors are well
      recognized hormonal effectors of growth hormone and are expressed in the
      mammalian spinal cord. The IGFBPs are a group of six genetically distinct
      proteins that bind IGFs and modulate their bioactivity. They appear in the brain
      during development, localize to the neuromuscular junction, and promote motor
      neuron survival. The benefit of IGF-I in amyotrophic lateral sclerosis ALS and
      its potential use in preventing motor neuron apoptosis in spinal cord injury
      dictates that studies of the presence and response of IGFBPs in that tissue be
      performed. METHODS: The IGFBPs in mouse spinal cord were analyzed by Western
      ligand blot, Western immunoblot, and reverse transcription-polymerase chain
      reaction at various time points from embryonic day 14 to postnatal day 30.
      RESULTS: Three IGFBPs with molecular masses of 24, 28, and 32 kDa were found, the
      latter two being the most prominent. The data indicate that these are IGFBP-4, 
      5, and -2. CONCLUSION: Both IGFBP-2 and BP-5 are developmentally regulated in
      mouse spinal cord, with higher levels of those at early embryonic stages
      indicating their potential role in development of the mouse spinal cord.

PMID- 10888944
TI  - Prediction of peripheral tears in the anulus of the intervertebral disc.
AB  - STUDY DESIGN: The mechanical behavior of age-related degeneration in the anulus
      of lumbar spine segments was investigated under extension with compressive
      preload by the finite-element method. OBJECTIVE: To investigate why peripheral
      tears are initiated in the anterior outer anulus in the early stage of life.
      SUMMARY OF BACKGROUND DATA: Age-related changes in the geometry, loading
      conditions, and material-mechanical properties of lumbar spine would change
      mechanical behavior of the anulus. METHODS: Two finite element models of the
      human lumbar segments (L3-L4), a young spine model for young adults and an old
      spine model for elder adults, were constructed. The anulus was modeled as
      laminate composite elements with 16 layers and six materials. The microfailure
      modes such as fiber breakage, fiber folding, layer (ply) failure, layer folding,
      and interlaminar delamination were predicted by principal strain of the anulus
      layer. RESULTS: Excessively high tensile principal strain in the transverse
      direction of the anulus layer, indicating layer failure, was predicted in the
      anterior outer anulus. The strain level was much higher in the young model than
      in the old model. Compressive principal strain in the transverse direction of the
      anulus layer, predicting layer folding, was found in the posterior and
      posterolateral anulus. CONCLUSIONS: Layer failure in the anterior outer anulus
      could occur in the early stage of life during extension with preload. This could
      then progress to formation of peripheral tears oriented at right angles to the
      fiber's direction.

PMID- 10888945
TI  - Postfracture instability of vertebrae with simulated defects can be predicted
      from computed tomography data.
AB  - STUDY DESIGN: Structural properties of vertebrae with simulated defects were
      measured from computed tomography data. Relations between structural properties
      and postfracture stability were tested using linear regressions. OBJECTIVES: To
      determine whether the postfracture stability of lumbar and thoracic vertebrae can
      be predicted from noninvasive, prefracture measurements of structural properties.
      SUMMARY OF BACKGROUND DATA: Sensitive and specific guidelines are needed that can
      predict fracture risk and spinal stability after pathologic fractures. Such
      guidelines may help determine whether treatment is needed to prevent neurologic
      complications. Simple measurements made from computed tomography data can predict
      the load-bearing capacity of intact vertebrae and vertebrae with simulated and
      actual metastatic defects. It is not known whether these same measurements can
      also predict postfracture stability. METHOD: Simulated metastatic defects were
      created in human three-vertebrae segments from the lumbar and thoracic spine.
      Axial rigidity was calculated from quantitative computed tomography data, and
      failure load and postfracture stability were measured. RESULTS: Postfracture
      stability was linearly correlated with both failure load (r2 = 0.3-0.6) and axial
      rigidity (r2 = 0.3-0.6). CONCLUSIONS: The postfracture stability of three
      vertebrae segments with simulated defects was modestly related to noninvasively
      measured, prefracture structural properties.

PMID- 10888946
TI  - Early intervention in whiplash-associated disorders: a comparison of two
      treatment protocols.
AB  - STUDY DESIGN: A prospective randomized trial in 97 patients with a whiplash
      injury caused by a motor vehicle collision. OBJECTIVES: The study evaluates early
      active mobilization versus a standard treatment protocol and the importance of
      early versus delayed onset of treatment. SUMMARY OF BACKGROUND DATA: There is no
      compelling evidence to date on the management of acute whiplash-associated
      disorders. The few studies describing treatment, however, provide evidence to
      support the recommendation that an active treatment in the acute stage is
      preferable to rest and a soft collar in most patients. METHODS: Patients were
      randomized to four groups. Active versus standard treatment and early (within 96
      hours) versus delayed (after 2 weeks) treatment. Measures of range of motion and
      pain were registered initially and at 6 months. RESULTS: Eighty-eight patients
      (91%) could be followed up at 6 months. Active treatment reduced pain more than
      standard treatment (P < 0.001). When type and onset of treatment were analyzed, a
      combined effect was seen. When active treatment was provided, it was better when
      administered early, and if standard treatment was provided, it was better when
      administered late for reduction of pain (P = 0.04) and increasing cervical
      flexion (P = 0.01). CONCLUSIONS: In patients with whiplash-associated disorders
      caused by a motor vehicle collision treatment with frequently repeated active
      submaximal movements combined with mechanical diagnosis and therapy is more
      effective in reducing pain than a standard program of initial rest, recommended
      use of a soft collar, and gradual self-mobilization. This therapy could be
      performed as home exercises initiated and supported by a physiotherapist.

PMID- 10888947
TI  - T-Saw laminoplasty for the management of cervical spondylotic myelopathy:
      clinical and radiographic outcome.
AB  - STUDY DESIGN: Independent evaluation of 18 patients with multilevel cervical
      spondylotic myelopathy who underwent threadwire T-saw laminoplasty. OBJECTIVES:
      Assess the efficacy of midline T-saw laminoplasty in non-Japanese patients based
      on clinical and radiographic criteria. SUMMARY OF BACKGROUND DATA: Spinous
      process-splitting laminoplasty has been well accepted in Japan. The results in
      non-Japanese patients are unknown. METHODS: A single physician performed
      independent clinical and radiographic evaluations at latest follow-up (mean, 24
      months). In addition to a patient self-assessment questionnaire, objective
      measures included physical examination, Pavlov's ratio, sagittal canal diameter
      (by computed tomography), cord compression index, cervical lordosis, range of
      motion, and complications. RESULTS: Progression of myelopathy was arrested in all
      patients. Patients reported improvement in strength (78%), dexterity (67%),
      numbness (83%), pain (83%), and gait (67%). Bowel and bladder compromise resolved
      in five of six patients. The mean Nurick score improved from 2.7 to 0.9 (P <
      0.001), and the mean Robinson pain score improved from 2.0 to 0.89 (P = 0.002).
      No patient required narcotic analgesics at latest follow-up compared with eight
      before laminoplasty. Objectively, 68% of patients with motor weakness regained
      normal strength (P = 0.001), whereas 50% regained normal sensation (P = 0.003).
      Radiographic canal expansion was verified by a statistically significant increase
      in the mean Pavlov ratio and osseous sagittal computed tomographic measurements.
      The mean cord compression index improved from 0.49 to 0.61 (P = 0.01). There was
      no significant change in mean cervical lordosis. Graft dislodgment or segmental
      instability did not occur. Complications included: infection (n = 1) and
      persistent postoperative motor root lesion at C5 (n = 1). CONCLUSIONS: T-saw
      laminoplasty appears to be a safe and effective method of arresting the
      progression of myelopathy and allowing marked functional improvement in most
      patients with multilevel cervical spondylotic myelopathy. [Key Words: cervical
      spine, decompression, laminoplasty, myelopathy, spondylosis]

PMID- 10888948
TI  - Do radiographic parameters correlate with clinical outcomes in adolescent
      idiopathic scoliosis?
AB  - STUDY DESIGN: A radiographic assessment has been developed to include coronal,
      sagittal, and axial parameters. OBJECTIVE: To determine the correlation of
      postoperative radiographic results and percentage postoperative radiographic
      improvement with patient clinical self-assessment. SUMMARY OF BACKGROUND DATA:
      With the increasing interest in outcome studies, the authors wanted to determine
      whether Scoliosis Research Society clinical questionnaire results would correlate
      with objective radiographic improvement. METHODS:  INCLUSION CRITERIA: adolescent
      idiopathic scoliosis treated with anterior or posterior instrumentation, a solid
      fusion, minimum 2-year follow-up, and a completed postoperative Scoliosis
      Research Society questionnaire. Seventy-eight patients met the criteria.
      Measurements included in the radiographic score: Cobb angles of the coronal
      curve, C7 to the center sacral vertical line, apical translation, apical
      vertebral rotation, T1 rib angle, end-instrumented vertebrae angulation,
      angulation of the disc below the end-instrumented vertebra, and curve type.
      Sagittal measurements included T2-T12, T5-T12, T2-T5, T12-L2, and L1-S1. RESULTS:
      The preoperative radiographic score of these 78 patients was mean 60.1 +/- 9.7
      (range 41-88, maximum radiographic score, 100). The 2-year postoperative
      radiographic score was mean 83.8 +/- 8.8 (range, 65-100). The median Scoliosis
      Research Society questionnaire score was 98 +/- 12.3 (range, 58-116, maximum
      score, 125, showing that the patient is highly satisfied and asymptomatic). The
      postoperative radiographic score versus the questionnaire score showed a Spearman
      rank correlation of 0.04 (P = 0.68, little or no correlation throughout).
      Percentage improvement of the radiographic score versus the questionnaire score
      showed a Spearman rank correlation of 0.1 (P = 0.38, little or no correlation
      throughout). CONCLUSION: In this initial group of patients, the radiographic
      assessment shows a significant improvement between preoperative and 2-year
      postoperative scores. However, little correlation between the radiographic
      assessment and the questionnaire scores was found in this adolescent population,
      suggesting that separate analyses of radiographic and clinical outcome data are
      required when evaluating results of postoperative scoliosis surgery.

PMID- 10888949
TI  - Can discography cause long-term back symptoms in previously asymptomatic
      subjects?
AB  - STUDY DESIGN: A prospective controlled study of patients without low back pain
      observed after experimental lumbar discography. OBJECTIVES: To determine whether
      discography may cause long-term low back symptoms in selected patients.
      BACKGROUND: Lumbar discography is generally considered safe, although
      controversial, with few complications. There is little information on long-term
      follow-up of asymptomatic patients after experimental discography. METHODS:
      Twenty-six patients without pre-existing low back pain were observed for 1 year
      after lumbar discography to determine the effects of lumbar discography in three
      experimental groups: 10 patients who had remote cervical spine surgery with
      excellent results (pain-free group); 10 patients who had the same surgery with
      poor results (chronic pain group); and 6 patients who had primary somatization
      disorders. Two control groups were also observed: a group of patients with
      somatization disorder who were similarly evaluated but without discography, a
      group of patients with low back pain observed for 1 year after discography
      without surgery. RESULTS: In the three experimental groups (no back pain before
      discography) no subject with normal psychometric testing had persistent pain
      after discography (0/11), whereas 6 (40%) of 15 with abnormal psychometric test
      results reported significant new low back pain. None of the pain-free group
      (0/10), 20% of the chronic neck pain group (2/10), and 66% of the somatization
      group (4/6) continued to have significant back pain 1 year after injection.
      Psychological testing and occupational disability strongly predicted continued
      pain after discography. The control groups had no significant change in low back
      symptomatology during the year of observation. CONCLUSION: Discography in a
      subject group without low back pain but with significant emotional and chronic
      pain problems may result in reports of significant back pain for at least 1 year
      after injection. Subjects with normal psychometric test results had no reports of
      significant long-term back pain after discography.

PMID- 10888950
TI  - The role of physical exercise and inactivity in pain recurrence and absenteeism
      from work after active outpatient rehabilitation for recurrent or chronic low
      back pain: a follow-up study.
AB  - STUDY DESIGN: An observational follow-up. OBJECTIVES: To analyze the role of
      physical exercise and inactivity on the long-term outcome after active outpatient
      low back rehabilitation. SUMMARY OF BACKGROUND DATA: There is considerable
      evidence documenting the efficacy of exercise in the conservative treatment of
      chronic low back pain, but the role of exercises after the guided treatment
      period on the long-term success and maintenance of the results is not known.
      METHODS: One hundred twenty-five patients with low back pain, who had
      participated in a 12-week active low back rehabilitation program, were asked
      about subjective pain and disability on the average of 14 months after the
      treatment. The outcomes were defined as a recurrence of persistent pain and work
      absenteeism, and a survival or failure analysis was performed between those who
      had continued exercising and who had been physically inactive. RESULTS:
      Recurrences of persistent pain during the follow-up period were fewer (P = 0.03)
      among those who had maintained regular exercise habits after the treatment than
      among those who had been physically inactive. Similarly, work absenteeism was
      less (P < 0.01) among physically active than among physically inactive persons.
      However, patients with good outcome in pain reduction after low back pain
      rehabilitation were more likely to participate in physical exercise. CONCLUSIONS:
      Exercises are beneficial after guided treatment in the maintenance of the results
      of active treatment for recurrent chronic low back pain in the long term, but
      those with less favorable outcome in rehabilitation are less likely to
      participate in exercises afterward. In active treatment programs, it is
      recommended that exercises be incorporated after the guided treatment.

PMID- 10888951
TI  - Relationship between functional evaluation measures and self-assessment in
      nonacute low back pain.
AB  - STUDY DESIGN: The correlations between objective biomechanical indicators of
      function and self-assessment scores were examined retrospectively for 91 subjects
      with nonacute low back pain. OBJECTIVES: To examine the correlation between self
      assessment, trunk range of motion (ROM), velocity, and complex mechanical
      coordination patterns of the spine in nonacute low back pain. SUMMARY OF
      BACKGROUND DATA: In low back pain, there is often little concordance between
      pain, physical impairment, and disability. Use of range of motion and velocity to
      enhance objectivity in impairment evaluations has been ineffectual. In this
      study, two hypotheses were examined: range of motion and velocity are
      controllable and inherently correlated with self-assessment; complex spinal
      coordination patterns such as range of lordosis cannot be controlled and are
      independent of self-assessment. METHODS: Self-assessment questionnaires were
      administered, and indexes of spinal motion and coordination were measured through
      skin marker kinematics. The correlation between self-assessments and
      biomechanical measures was determined. RESULTS: Self-assessments of function were
      significantly correlated with parameters prone to regulation: range of motion,
      velocity, and load lifted. In contrast, little correlation was found with
      measures of complex spinal coordination less susceptible to conscious or
      affective regulation, namely, range of lordosis and estimated segmental mobility.
      This effect was magnified with increased load. Self-assessment scores were
      significantly poorer among insurance referrals, regardless of functional status.
      CONCLUSIONS: Simple parameters of the functional examination, such as range of
      motion and velocity, are strongly correlated with cognitive state, and thus the
      information they supply is less than ideal. Complex spinal coordination is a
      better indicator of the degree of spinal dysfunction and enhances the process of
      differentiating between pain, disability, and functional impairment.

PMID- 10888952
TI  - Deep vein thrombosis after major spinal surgery: incidence in an East Asian
      population.
AB  - STUDY DESIGN: A prospective study of 313 patients who underwent major spinal
      surgery. OBJECTIVES: To determine the incidence of deep vein thrombosis after
      major spinal surgery in an east Asian population without antithrombotic
      prophylaxis. SUMMARY OF BACKGROUND DATA: Spinal surgery has been associated with
      few thrombotic complications (2-14%) compared with other reconstructive surgeries
      (20-70%). It has also been well documented that the incidence of deep vein
      thrombosis in east Asians (10%) is lower than in westerners (20-70%) in total
      joint replacements. There has been no previous report on the incidence of deep
      vein thrombosis after reconstructive spinal surgery in east Asians. METHODS:
      Three hundred thirteen patients who underwent major spinal surgery were evaluated
      prospectively. All patients were examined with duplex ultrasonography assessments
      of both lower extremities. No specific antithrombotic prophylaxis were used in
      any patients before or after surgery. RESULTS: There were four patients with
      positive findings of deep vein thrombosis on duplex ultrasonography, and there
      was only one with clinically symptomatic deep vein thrombosis. The overall
      incidence of thrombotic complications was 1.3%, and the incidence of symptomatic
      deep vein thrombosis was 0.3%. CONCLUSION: Considering the low rate of deep vein
      thrombosis, routine screening and prophylaxis for deep vein thrombosis appears
      unwarranted in east Asians before or after major spinal surgery.

PMID- 10888953
TI  - Appropriateness of surgery for sciatica: reliability of guidelines from expert
      panels.
AB  - STUDY DESIGN: Reliability study of guidelines development. OBJECTIVE: To compare
      criteria for low back surgery between two expert panels. BACKGROUND: Reliability
      of expert panels for determining appropriateness of indications for surgical
      procedures has heretofore received little attention. METHODS: Two
      multidisciplinary expert panels of similar composition were convened, in the
      United States and in Switzerland, to evaluate the appropriateness of 720 distinct
      clinical scenarios involving sciatica. Each indication was assigned to a category
      of appropriate, uncertain, and inappropriate. The appropriateness of the 720
      theoretical scenarios were compared between the two panels, and both sets of
      criteria were applied to two series of actual cases. RESULTS: Seventy-nine
      percent (n = 566) of the 720 theoretical indications were assigned to identical
      categories of appropriateness by both panels (kappa = 0.63; P < 0.001). Only 2 of
      the 720 scenarios elicited frank disagreement. The percentage of the 720
      indications that were considered appropriate differed between the two panels
      (U.S.: 3%; Swiss: 11%, P < 0.001), as did the percentage of intrapanel agreement
      for indications (U.S.: 51%, Swiss: 64%, P < 0.001). When the same theoretical
      scenarios were matched with two series of actual cases (n = 181 and 149)
      agreement was moderate (kappa = 0.46) to fair (kappa = 0.30). CONCLUSION: There
      was substantial agreement on the appropriateness of surgery for theoretical cases
      of sciatica between independent expert panels from two countries. A better
      understanding of discordant ratings, especially for actual cases, should precede
      attempts at transposing recommendations emanating from a panel in one country to
      another.

PMID- 10888954
TI  - Outcome of one-level posterior lumbar interbody fusion for spondylolisthesis and
      postoperative intervertebral disc degeneration adjacent to the fusion.
AB  - STUDY DESIGN: Review of the clinical and radiologic records of patients who
      underwent one-level posterior lumbar interbody fusion (PLIF) at L4-L5. OBJECTIVE:
      To determine whether adjacent intervertebral disc degeneration after PLIF affects
      the clinical results, and whether preoperative caudal disc (L5-S1) degeneration
      affects postoperative clinical results. SUMMARY OF BACKGROUND DATA: There is
      little reliable information in the literature regarding clinical results and
      adjacent disc degeneration after PLIF. METHODS: Forty-five patients who underwent
      L4-L5 PLIF for spondylolisthesis with more than 5 years of postoperative
      observation were included in this study. PLIF was performed in conjunction with
      posterior instrumentation. The posterior lumbar intervertebral grafting was
      performed using both autograft and a ceramic spacer. Intervertebral disc heights
      at L2-L3, L3-L4, and L5-S1 were measured before and after surgery. The patients
      were divided into two groups based on the presence or absence of the preoperative
      L5-S1 narrowing. Correlation between clinical status evaluated by the recovery
      rate of the Japanese Orthopedic Association (JOA) score and disc heights were
      determined. RESULTS: All intervertebral disc heights adjacent to the fusion
      decreased after surgery (P < 0.05). However, no significant correlation was seen
      between clinical results estimated by the recovery rate and postoperative disc
      narrowing. There was also no significant difference in clinical results between
      patients with or without preoperative L5-S1 narrowing. CONCLUSIONS: There is no
      evidence from the results that postoperative narrowing of the adjacent disc and
      preoperative narrowing of the L5-S1 disc affects the clinical outcome of L4-L5
      PLIF.

PMID- 10888955
TI  - Unilateral versus bilateral pedicle screw fixation in lumbar spinal fusion.
AB  - STUDY DESIGN: A prospective study of 87 patients who underwent unilateral or
      bilateral pedicle screw fixation. OBJECTIVES: To determine whether unilateral
      pedicle screw fixation is comparable with bilateral fixation in one- or two
      segment lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: Clinical results for
      unilateral variable screw placement instrumentation in isolated L4-L5 fusion have
      been reported to be as good as those for bilateral instrumentation. However,
      unilateral instrumentation may not be recommended for multilevel fusion. METHODS:
      Eighty-seven patients were assigned to either unilateral (n = 47) or bilateral (n
      = 40) pedicle screw instrumentation groups. Two kinds of pedicle screw system
      (Moss Miami, DePuy, Warsaw, IN, and Steffee VSP, AcroMed, Cleveland, OH) were
      used. Operating time, blood loss, duration of hospital stay, clinical outcomes,
      fusion rates, complication rates, and medical expenses were studied and tested
      with independent sample t test and chi2 test. RESULTS: There were no significant
      differences between the two groups in blood loss, clinically satisfactory
      results, fusion rate, and complication rate. There were significant differences
      in duration of operating time, duration of hospital stay, and medical expenses.
      The number of fusion segments or kinds of instrumentation did not affect the
      fusion rate or clinical outcomes. CONCLUSIONS: Unilateral pedicle screw fixation
      was as effective as bilateral pedicle screw fixation in lumbar spinal fusion
      independent of the number of fusion segments (one or two segments) or pedicle
      screw systems. Based on the results of this study, unilateral fixation could be
      used in two-segment lumbar spinal fusion.

PMID- 10888956
TI  - Pseudoaneurysm of the deep circumflex iliac artery: a rare complication at an
      anterior iliac bone graft donor site.
AB  - STUDY DESIGN: The formation of a pseudoaneurysm of the deep circumflex iliac
      artery after the harvesting of an anterior iliac bone graft for spinal fusion is
      reported. OBJECTIVE: To describe a rare complication at an iliac bone graft donor
      site. SUMMARY OF BACKGROUND DATA: The iliac bone is a common site for harvesting
      bone for spinal surgery. Although many complications have been reported, vascular
      injuries associated with this procedure are rare. To the authors' knowledge, deep
      circumflex iliac artery injury has not been reported as a complication. METHODS:
      A 70-year-old man with cervical myelopathy underwent anterior cervical
      decompression and fusion with an anterior iliac bone graft. Fracture displacement
      of the anterior superior iliac spine at the donor site was noted 1 week after a
      second operation, which was performed to reduce the displaced grafted bone. Five
      months after the second operation, he reported pain and swelling at the donor
      site. Removal of a hematoma was attempted, which led to massive bleeding that was
      difficult to control. RESULTS: Angiography demonstrated a pseudoaneurysm of the
      deep circumflex iliac artery. Selective embolization of the artery was performed,
      and the bleeding was arrested. CONCLUSIONS: Vascular injury after anterior iliac
      bone harvesting is rare but can occur. Selective arterial embolization was an
      effective solution.

PMID- 10888957
TI  - Lumbar paraspinal myonecrosis after abdominal vascular surgery: a case report.
AB  - STUDY DESIGN: Case report. OBJECTIVES: Lumbar paraspinal myonecrosis after
      abdominal vascular surgery. SUMMARY OF BACKGROUND DATA: Lumbar paraspinal
      myonecrosis does not appear to have been reported previously. METHODS: A patient
      who had severe back pain after abdominal vascular surgery was observed with
      computed tomographic scans and histologic examination of a specimen obtained in
      open biopsy. RESULTS: Computed tomographic scans of the lumbar region
      demonstrated muscle swelling of the unilateral paraspinal compartment. Histologic
      examinations of affected muscle revealed fresh ischemic necrosis. A compartmental
      syndrome was considered from the patient's clinical presentation and radiographic
      and histologic features. An accompanying secondary infection led to an extensive
      abscess in the paraspinal compartment. The patient resumed active daily life
      after aggressive debridements of infected and necrotic muscles. CONCLUSIONS: A
      compartmental syndrome in the paraspinal muscle should be kept in mind as a
      potential cause of acute back pain especially after abdominal vascular surgery.

PMID- 10888958
TI  - Endoscopic approaches to metastatic thoracic disease.
AB  - Traditional approaches to thoracic metastases and spinal cord compression have
      been well worked out and validated in the literature. Anterior decompression is
      clearly superior to laminectomy; vertebrectomy and reconstruction are indicated
      for sagittal collapse, instability, and pain; and surgical decompression is
      necessary in cases of bony impingement. The role of endoscopic and minimally
      invasive techniques in treatment of metastatic disease is evolving. Dr. Lieberman
      advocates the use of thoracoscopic anterior approaches as the principal
      application in these patients, whereas Dr. McLain has found that endoscopic
      assistance has vastly improved his results with posterolateral decompression. The
      two authors weigh the relative advantages and disadvantages of these approaches
      for the selected patient with metastatic thoracic disease.

PMID- 10888959
TI  - Controversy: endoscopic approaches to metastatic thoracic disease
AB  - Traditional approaches to thoracic metastases and spinal cord compression have
      been well worked out and validated in the literature. Anterior decompression is
      clearly superior to laminectomy; vertebrectomy and reconstruction are indicated
      for sagittal collapse, instability, and pain; and surgical decompression is
      necessary in cases of bony impingement. The role of endoscopic and minimally
      invasive techniques in treatment of metastatic disease is evolving. Dr. Lieberman
      advocates the use of thoracoscopic anterior approaches as the principal
      application in these patients, whereas Dr. McLain has found that endoscopic
      assistance has vastly improved his results with posterolateral decompression. The
      two authors weigh the relative advantages and disadvantages of these approaches
      for the selected patient with metastatic thoracic disease.

PMID- 10888960
TI  - Advances in secondary spinal cord injury: role of apoptosis.
AB  - The outcome of spinal cord injury depends on the extent of secondary damage
      produced by a series of cellular and molecular events initiated by the primary
      trauma. This article reviews the evidence that secondary spinal cord injury
      involves the apoptotic as well as necrotic death of neurons and glial cells. Also
      discussed are the major factors that can contribute to cell death, such as
      glutamatergic excitotoxicity, free radical damage, cytokines, and inflammation.
      The development of innovative therapeutic strategies to reduce secondary spinal
      cord injury depends on an increased understanding of secondary injury mechanisms
      at the molecular and biochemical level. Such therapeutic interventions may
      include the use of antiapoptotic drugs, free radical scavengers, and anti
      inflammatory agents. These could be targeted to block key reactions on cellular
      and molecular injury cascades, thus reducing secondary tissue damage, minimizing
      side effects, and improving functional recovery.

PMID- 10888962
TI  - Imagery

PMID- 10888961
TI  - Re: The ligaments and annulus fibrosus of human adult cervical intervertebral
      discs (Spine 1999;24;619-28)

PMID- 10888963
TI  - Case of the month. The autopsy and new technology: all that glitters is not a
      gold standard.

PMID- 10888964
TI  - The trouble with triglycerides.

PMID- 10888965
TI  - Angiotensin II receptor blockers: equal or preferred substitutes for ACE
      inhibitors?

PMID- 10888966
TI  - The influence of anxiety and depression on outcomes of patients with coronary
      artery disease.

PMID- 10888967
TI  - Ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia is a common complication in intensive care units,
      occurring in 9% to 24% of patients intubated for longer than 48 hours. Because of
      this large disease burden and the resultant attributable morbidity and mortality,
      there is great interest in accurately diagnosing, treating, and preventing this
      complication. More severely ill patients tend to develop ventilator-associated
      pneumonia, and identified risk factors include prolonged mechanical ventilation,
      reintubation after failed extubation, and a few other clinical variables. The
      efficacy of diagnostic and preventive strategies is somewhat controversial.
      Diagnosis by invasive methods requires a considerable commitment of resources but
      can potentially reduce cost of care; however, mortality benefit from this
      approach has not been demonstrated. As such, in most institutions, ventilator
      associated pneumonia is best diagnosed using traditional clinical criteria.
      Prompt administration of appropriate antibiotics seems to be the only
      intervention that alters outcome once the diagnosis is established. Several
      strategies seem to reduce pneumonia incidence; however, mortality and cost
      benefits have yet to be convincingly shown.

PMID- 10888968
TI  - Do triglycerides provide meaningful information about heart disease risk?
AB  - BACKGROUND: Prior research suggests that adding triglyceride determinations to
      measurements of total cholesterol and cholesterol subfractions may improve the
      prediction of coronary heart disease (CHD). OBJECTIVE: To determine the
      additional value of measuring triglyceride levels, in addition to cholesterol
      levels and subfractions, for predicting CHD. STUDY DESIGN: A set of secondary
      analyses of previously reported studies. METHODS: We performed secondary analyses
      of data from the Multiple Risk Factor Intervention Trial, the Lipid Research
      Clinics Coronary Primary Prevention Trial, and the Lipid Research Clinics
      Prevalence and Mortality Follow-Up Study. Predictor variables included the levels
      of fasting triglycerides, total cholesterol, low-density lipoprotein cholesterol,
      high-density lipoprotein cholesterol, and fasting blood glucose; age; blood
      pressure; cigarette smoking; body mass index; and postmenopausal estrogen use.
      Analytic methods included Cox proportional hazards models, calculation of
      stratified crude incidence rates, and measurement of the area under the receiver
      operating characteristic curve. MAIN OUTCOME MEASURES: Outcome variables were
      fatal and nonfatal myocardial infarctions. RESULTS: With few exceptions, no
      significant interactions between cholesterol subfractions and triglyceride levels
      were found and receiver operating characteristic curve analyses revealed that
      triglyceride measurements did not improve discrimination between those subjects
      who did and did not suffer CHD events. In men, categorical analyses employing
      both triglyceride and cholesterol levels were similar to those using cholesterol
      categories alone. In the one study of women, those subjects with both a high-risk
      cholesterol profile and high triglyceride levels were more likely to have a CHD
      event, though this finding was based on fewer subjects and CHD events.
      CONCLUSION: These data suggest that, in men, measurement of serum triglyceride
      levels does not provide clinically meaningful information about CHD risk beyond
      that obtainable by measurement of serum cholesterol subfractions alone.

PMID- 10888969
TI  - Exercise and weight loss reduce blood pressure in men and women with mild
      hypertension: effects on cardiovascular, metabolic, and hemodynamic functioning.
AB  - BACKGROUND: Lifestyle modifications have been recommended as the initial
      treatment strategy for lowering high blood pressure (BP). However, evidence for
      the efficacy of exercise and weight loss in the management of high BP remains
      controversial. METHODS: One hundred thirty-three sedentary, overweight men and
      women with unmedicated high normal BP or stage 1 to 2 hypertension were randomly
      assigned to aerobic exercise only; a behavioral weight management program,
      including exercise; or a waiting list control group. Before and following
      treatment, systolic and diastolic BPs were measured in the clinic, during daily
      life, and during exercise and mental stress testing. Hemodynamic measures and
      metabolic functioning also were assessed. RESULTS: Although participants in both
      active treatment groups exhibited significant reductions in BP relative to
      controls, those in the weight management group generally had larger reductions.
      Weight management was associated with a 7-mm Hg systolic and a 5-mm Hg diastolic
      clinic BP reduction, compared with a 4-mm Hg systolic and diastolic BP reduction
      associated with aerobic exercise; the BP for controls did not change.
      Participants in both treatment groups also displayed reduced peripheral
      resistance and increased cardiac output compared with controls, with the greatest
      reductions in peripheral resistance in those in the weight management group.
      Weight management participants also exhibited significantly lower fasting and
      postprandial glucose and insulin levels than participants in the other groups.
      CONCLUSIONS: Although exercise alone was effective in reducing BP, the addition
      of a behavioral weight loss program enhanced this effect. Aerobic exercise
      combined with weight loss is recommended for the management of elevated BP in
      sedentary, overweight individuals.

PMID- 10888970
TI  - Impact of Helicobacter pylori infection on gastric cancer incidence in a general
      Japanese population: the Hisayama study.
AB  - BACKGROUND: Several nested case-control studies have reported the potentially
      causal relationship between Helicobacter pylori infection and the development of
      gastric cancer. However, there has been no prospective study evaluating this
      issue. The purpose of this study is to examine the impact of H pylori infection
      on gastric cancer occurrence in a general Japanese population (Hisayama, Japan)
      stratified according to sex, using a prospective study design. METHODS: A total
      of 2602 subjects aged 40 years or older (1070 men; mean age, 57 years; 1532
      women; mean age, 59 years) without a history of gastrectomy or gastric cancer
      were classified according to the status of the serum IgG antibodies to H pylori
      and observed prospectively for 9 years from 1988. RESULTS: Infection of H pylori
      was more common in men (71.5%) than in women (62.5%; P<.001). The age-adjusted
      incidence of gastric cancer for men (5.3 per 1000 person-years) was 4-fold higher
      than that for women (1.3; P<.001). In men, the age-adjusted incidence of gastric
      cancer was significantly higher in the subjects with H pylori infection than in
      those without it (6.2 vs 2.5; relative risk, 2.59 [95% confidence interval, 1.03
      6.50]), whereas no significant difference was observed in women (1.2 vs 1.1;
      relative risk, 0.99 [95% confidence interval, 0.36-2.68]). These results were
      similar even after controlling for other risk factors in multivariate analysis.
      It was estimated that 40.1% of gastric cancers for men in this cohort were
      attributable to H pylori infection. CONCLUSION: A significant relationship exists
      between infection with H pylori and subsequent occurrence of gastric cancer for
      men but not for women in this Japanese population.

PMID- 10888971
TI  - Short- and long-term survival after cardiopulmonary resuscitation.
AB  - BACKGROUND: The objective was to evaluate the effect of patient characteristics
      and other factors on cardiopulmonary resuscitation (CPR) survival, hospital
      discharge survival and function, and long-term survival. METHODS: All patients 18
      years and older experiencing in-hospital CPR from December 1983 through November
      1991 at Marshfield Medical Center (Marshfield Clinic and adjoining St Joseph's
      Hospital), Marshfield, Wis, were selected. We performed a retrospective medical
      record review and augmented these data with updated vital status information.
      MAIN OUTCOME MEASURES: Cardiopulmonary resuscitation survival, hospital discharge
      survival and function, and long-term survival. RESULTS: Of 948 admissions during
      which CPR was performed, 61.2% of patients survived the arrest and 32.2% survived
      to hospital discharge. Mechanism of arrest was the most important variable
      associated with hospital discharge. Patients with pulseless electrical activity
      had the worst chance of hospital discharge, followed by those with asystole and
      bradycardia. Follow-up information was available for 298 patients who survived to
      discharge. One year after hospital discharge, 24.5% of patients, regardless of
      age, had died. Survival was 18.5% at 7 years in those 70 years or older, compared
      with 45.4% in those aged 18 to 69 years. Heart rhythm at the time of arrest
      strongly influenced long-term survival. Bradyarrhythmias produced a nearly 2-fold
      increased mortality risk compared with normal sinus rhythm. CONCLUSIONS: Survival
      until hospital discharge after CPR at our institution during an 8-year period was
      higher than previously reported for other institutions. Long-term survival after
      discharge was equal to or higher than reported estimates from other institutions.
      Hospital admission practices and selection of patients receiving CPR may account
      for these findings.

PMID- 10888972
TI  - Screening for alcohol problems in primary care: a systematic review.
AB  - BACKGROUND: Primary care physicians can play a unique role in recognizing and
      treating patients with alcohol problems. OBJECTIVE: To evaluate the accuracy of
      screening methods for alcohol problems in primary care. METHODS: We performed a
      search of MEDLINE for years 1966 through 1998. We included studies that were in
      English, were performed in primary care, and reported the performance
      characteristics of screening methods for alcohol problems against a criterion
      standard. Two reviewers appraised all articles for methodological content and
      results. RESULTS: Thirty-eight studies were identified. Eleven screened for at
      risk, hazardous, or harmful drinking; 27 screened for alcohol abuse and
      dependence. A variety of screening methods were evaluated. The Alcohol Use
      Disorders Identification Test (AUDIT) was most effective in identifying subjects
      with at-risk, hazardous, or harmful drinking (sensitivity, 51%-97%; specificity,
      78%-96%), while the CAGE questions proved superior for detecting alcohol abuse
      and dependence (sensitivity, 43%-94%; specificity, 70%-97%). These 2 formal
      screening instruments consistently performed better than other methods, including
      quantity-frequency questions. The studies inconsistently adhered to
      methodological standards for diagnostic test research: 3 (8%) provided a full
      description of patient spectrum (demographics and comorbidity), 30 (79%) avoided
      workup bias, 12 (of 34 studies [35%]) avoided review bias, and 21 (55%) performed
      an analysis in pertinent clinical subgroups. CONCLUSIONS: Despite methodological
      limitations, the literature supports the use of formal screening instruments over
      other clinical measures to increase the recognition of alcohol problems in
      primary care. Future research in this field will benefit from increased adherence
      to methodological standards for diagnostic tests.

PMID- 10888973
TI  - Excess triiodothyronine as a risk factor of coronary events.
AB  - BACKGROUND: Abnormalities in cardiac function, eg, arrhythmias and congestive
      heart failure, often accompany thyrotoxicosis. A relationship between thyroid
      hormone excess and the cardiac complications of angina pectoris and myocardial
      infarction (MI) remains largely speculative. METHODS: The results of thyroid
      function studies on blood samples drawn from a total of 1049 patients (aged 40
      years or older) immediately on emergency medical admission were related to
      frequencies of angina pectoris and myocardial infarction as determined according
      to current diagnostic algorithms. After 3 years, those patients who had initially
      presented with angina pectoris or acute MI were observed for subsequent coronary
      events; of these (n=185), 98% of the subjects (n=181) could be reevaluated.
      RESULTS: On hospital admission, the relative rate of angina pectoris and MI was
      markedly high (odds ratio, 2.6; 95% confidence interval, 1.3-5.2; P=.007) in
      patients with elevated serum free and total triiodothyronine (T(3)) levels. An
      initially elevated free T(3) level was a risk factor for subsequent coronary
      events during the 3-year follow-up (adjusted odds ratio, 4.8; 95% confidence
      interval, 1.3-17.4; P=.02). CONCLUSIONS: An elevation of serum free T(3) levels
      at hospital admission is associated with a 2.6-fold greater likelihood of the
      presence of a coronary event. Moreover, an initially elevated T(3) level is
      associated with a 3-fold higher risk of developing a subsequent coronary event
      during the next 3 years. Excess T(3) seemed to be a factor associated with the
      development and progression of acute myocardial ischemia.

PMID- 10888974
TI  - Wound myiasis in urban and suburban United States.
AB  - BACKGROUND: The epidemiologic characteristics of human myiasis in the United
      States remain undefined. OBJECTIVE: To describe the most common clinical
      conditions associated with human myiasis and the causative maggot species.
      METHODS: Multicenter, prospective observational study of urban and suburban
      patients who were infested with maggots. RESULTS: Forty-two cases of US-acquired
      myiasis were collected from 20 participating centers. Most infestations occurred
      within preexisting wounds. No cases of tissue invasion were recorded. Host age
      averaged 60 years, with a male-female ratio of 5.5:1. Homelessness, alcoholism,
      and peripheral vascular disease were frequent cofactors. Two patients (5%) were
      hospitalized at the time of their infestation. The most common species was
      Phaenicia sericata (green blowfly; family: Calliphoridae). Other blowflies, flesh
      flies (Sarcophagidae), and humpbacked flies (Phoridae) also were identified. In 6
      cases, 2 coinfesting species were identified. CONCLUSIONS: Results of this
      prospective study of myiasis differ significantly from those of our analysis of
      previously published reports and suggest that most cases of human myiasis are
      caused by noninvasive blowflies laying eggs in preexisting wounds. Five percent
      of infestations were nosocomially acquired and not necessarily associated with
      patient neglect.

PMID- 10888975
TI  - Immune function and vaccine responses in healthy advanced elderly patients.
AB  - BACKGROUND: Decline in immune function has been reported to predictably accompany
      advancing age. However, to our knowledge, few studies have specifically
      characterized the rapidly expanding advanced elderly population or controlled
      adequately for concurrent diseases. OBJECTIVE: To assess whether successfully
      reaching an advanced age in good health is associated with preserved immune
      function. METHODS: We prospectively compared in vivo with in vitro variables of
      immune function in 29 healthy, independently living elderly subjects (mean age,
      80 years; age range, 75-103 years) and in 21 healthy young control subjects (mean
      age, 29 years; age range, 25-35 years) in a Veterans Affairs Medical Center.
      RESULTS: In vivo, among elderly and young subjects, numbers of total white blood
      cells, monocytes, lymphocytes, and lymphocyte subsets (CD4(+) and CD8(+) T
      lymphocytes and CD20(+) B cells) were similar, as were levels of total serum IgG
      and IgM. Only levels of serum IgA were higher in the elderly subjects (3.0 vs 1.7
      g/L; P=.001). Functionally, both groups showed vigorous responses to protein
      (tetanus and diphtheria toxoids) and polysaccharide (23-valent pneumococcal)
      vaccines. Although levels varied, the fold increases in vaccine antigen-specific
      IgG were not significantly different in young and elderly subjects, and the
      avidities of IgG to pneumococcal polysaccharides 14 and 19F were similar before
      and after vaccination. In vitro, proliferative responses of blood mononuclear
      cells to T-lymphocyte and B-cell mitogens (pokeweed mitogen, Staphylococcus
      aureus Cowan strain I, and S aureus Cowan strain I plus interleukin 2), and
      lipopolysaccharide-induced production of tumor necrosis factor alpha, were
      comparable in elderly vs young subjects. CONCLUSION: Successful aging, defined by
      reaching an advanced age with one's overall health intact, may be associated with
      preserved immune function and adequate responses to vaccines.

PMID- 10888976
TI  - A prospective study of cytomegalovirus, herpes simplex virus 1, and coronary
      heart disease: the atherosclerosis risk in communities (ARIC) study.
AB  - BACKGROUND: Conflicting evidence exists implicating infectious disease in the
      pathological processes leading to coronary heart disease (CHD). The objective of
      this article is to describe the relationship of previous infection with
      cytomegalovirus (CMV) and herpes simplex virus 1 to incident CHD in a population
      based cohort study. METHODS: Using a nested case-cohort design from the
      Atherosclerosis Risk in Communities Study, antibody levels to CMV and herpes
      simplex virus 1 were determined in serum samples that had been frozen at the
      baseline examination in participants free of CHD. Determinations were made in
      those who developed incident CHD (n=221) during follow-up of up to 5 years from
      baseline and in a stratified random sample of all participants (n=515). RESULTS:
      The population with the highest antibody levels of CMV (approximately the upper
      20%) showed an increased relative risk (RR) of CHD of 1.76 (95% confidence
      interval, 1.00-3.11), adjusting for age, sex, and race. After adjustment for
      additional covariates of hypertension, diabetes, years of education, cigarette
      smoking, low-density lipoprotein and high-density lipoprotein cholesterol levels,
      and fibrinogen level, the RR increased slightly. Based on a priori hypotheses,
      the RR of CHD at the highest antibody levels in individuals with diabetes was
      particularly large but with wide confidence intervals (RR, 9.2; 95% confidence
      interval, 1.8-47.0), and the interaction between high levels of antibody to CMV
      and diabetes was statistically significant (P=.05). There was no association of
      CHD with the highest herpes simplex virus 1 antibody levels (adjusted RR, 0.77;
      95% confidence interval, 0.36-1.62). CONCLUSIONS: High levels of CMV antibodies
      are significantly associated with incident CHD. Infection with CMV, particularly
      in more susceptible disease states such as diabetes, may be an important risk
      factor for CHD.

PMID- 10888977
TI  - A population-based study of the effectiveness of inferior vena cava filter use
      among patients with venous thromboembolism.
AB  - BACKGROUND: There are few population-based data regarding the effectiveness of
      inferior vena cava filter use in the prevention of symptomatic pulmonary
      embolism. OBJECTIVE: To determine the 1-year cumulative incidence of
      rehospitalization for venous thrombosis or pulmonary embolism among patients with
      thromboembolism treated with a vena cava filter compared with the incidence in a
      control population with thromboembolism. PATIENTS AND METHODS: Population-based
      retrospective analysis of linked hospital discharge abstracts in California. From
      January 1, 1991, through December 30, 1995, 3632 patients were treated with a
      filter and 64,333 controls were admitted with a principal diagnosis of venous
      thromboembolism. RESULTS: Filter-treated patients had significantly greater
      comorbidity, with a higher frequency of previous pulmonary embolism, recent major
      bleeding, malignant neoplasm, and stroke. Patients who initially manifested
      pulmonary embolism were significantly more likely to be rehospitalized for
      pulmonary embolism than patients with an initial diagnosis of venous thrombosis
      alone, among filter-treated patients (relative risk, 6.72; 95% confidence
      interval, 3.61-12.49) and controls (relative risk, 5.30; 95% confidence interval,
      4.61-6.10). Risk-adjusted proportional hazards modeling showed no significant
      difference between filter-treated patients and controls in the relative hazard of
      rehospitalization for pulmonary embolism. However, filter placement was
      associated with a significantly higher relative hazard of rehospitalization for
      venous thrombosis among patients who initially manifested pulmonary embolism
      (relative hazard, 2.62; 95% confidence interval, 2.09-3.29), but not among those
      who presented with venous thrombosis (relative hazard, 1.14; 95% confidence
      interval, 0.92-1.43). CONCLUSIONS: Insertion of a vena cava filter was not
      associated with a significant reduction in the 1-year incidence of
      rehospitalization for pulmonary embolism. Use of a filter was associated with a
      higher incidence of rehospitalization for venous thrombosis, but only among
      patients who initially manifested pulmonary embolism. A prospective clinical
      study is needed to determine the efficacy of filter use among patients with
      pulmonary embolism who do not meet strict guidelines for insertion of a vena cava
      filter.

PMID- 10888978
TI  - Prophylactic antithrombotic therapy for patients with systemic lupus
      erythematosus with or without antiphospholipid antibodies: do the benefits
      outweigh the risks? A decision analysis.
AB  - BACKGROUND: A high incidence of both arterial and venous thromboembolic events
      has been reported in patients with systemic lupus erythematosus (SLE), but the
      risks and benefits of primary prophylactic antithrombotic therapy have not been
      assessed. We measured the clinical benefit of 3 antithrombotic regimens in
      patients with SLE without antiphospholipid antibodies, with anticardiolipin
      antibodies, or with lupus anticoagulant. METHODS: A Markov decision analysis was
      used to evaluate prophylactic aspirin therapy, prophylactic oral anticoagulant
      therapy, and observation. Input data were obtained by literature review. Clinical
      practice was simulated in a hypothetical cohort of patients with SLE who had not
      experienced any previous episode of arterial or venous thromboembolic events. For
      each strategy, we measured numbers of thromboembolic events prevented and major
      bleeding episodes induced, and quality-adjusted survival years. RESULTS:
      Prophylactic aspirin therapy was the preferred strategy in all settings, the
      number of prevented thrombotic events exceeding that of induced bleeding
      episodes. In the baseline analysis (40-year-old patients with SLE), the gain in
      quality-adjusted survival years achieved by prophylactic aspirin compared with
      observation ranged from 3 months in patients without antiphospholipid antibodies
      to 11 months in patients with anticardiolipin antibodies or lupus anticoagulant.
      Prophylactic oral anticoagulant therapy provided better results than prophylactic
      aspirin only in patients with lupus anticoagulant and an estimated bleeding risk
      of 1% per year or less. CONCLUSIONS: Prophylactic aspirin should be given to all
      patients with SLE to prevent both arterial and venous thrombotic manifestations,
      especially in patients with antiphospholipid antibodies. In selected patients
      with lupus anticoagulant and a low bleeding risk, prophylactic oral anticoagulant
      therapy may provide a higher utility.

PMID- 10888979
TI  - Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and
      lipodystrophy: a 5-year cohort study.
AB  - BACKGROUND: Although human immunodeficiency virus (HIV)-related morbidity and
      mortality rates in patients with advanced HIV infection who are treated with
      combination antiretroviral drugs have declined, significant metabolic adverse
      effects associated with these regimens have been increasingly recognized.
      However, since data from patients studied before and after initiation of protease
      inhibitor (PI) therapy are scant, the true effect of PIs on these metabolic
      changes remains unknown. OBJECTIVES: To examine temporal trends in serum glucose
      and lipid levels after initiation of PI therapy, to assess whether changes are
      independent of virological response and improvement in disease severity, and to
      determine risk factors associated with the development of hyperglycemia,
      hyperlipidemia, and lipodystrophy. METHODS: A 5-year historical cohort analysis
      in a population of 221 HIV-infected patients observed in the Infectious Diseases
      Clinic of a tertiary care center from October 1, 1993, through July 31, 1998.
      Clinical and laboratory data were retrieved from medical records and a
      computerized database. The main outcome measure was the incidence of
      hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and lipodystrophy.
      Adjusted incidence rate ratios (IRRs) were estimated by means of Poisson
      regression. In addition, mixed regression analyses were performed to examine
      effects of PIs on serum lipid and glucose levels, modeled as continuous outcomes.
      RESULTS: The cumulative incidence of new-onset hyperglycemia,
      hypercholesterolemia, hypertriglyceridemia, and lipodystrophy was 5%, 24%, 19%,
      and 13%, respectively. Most of these events occurred after initiation of PI
      therapy. Protease inhibitors were independently associated with hyperglycemia
      (adjusted IRR, 5.0; 95% confidence interval [CI], 1. 3-19.4),
      hypercholesterolemia (adjusted IRR, 2.8; 95% CI, 1.5-5.2), hypertriglyceridemia
      (adjusted IRR, 6.1; 95% CI, 3.1-11.7), and lipodystrophy (adjusted IRR, 5.1; 95%
      CI, 1.9-13.9). Anabolic steroids and psychotropic medications were also
      associated with lipodystrophy. Inclusion of potential intermediate variables (eg,
      virological suppression and increase in body weight) did not reduce the magnitude
      of the association with PIs. The association between hypertriglyceridemia and
      ritonavir was stronger than for other PIs (Wald test, P=.02). In contrast, the
      incidence of hyperglycemia, hypercholesterolemia, and lipodystrophy did not vary
      significantly across different PIs. Longitudinal mixed models confirmed that
      serum lipid levels were more substantially affected by antiretroviral therapy,
      particularly PIs, than serum glucose levels. Similarly, controlling for surrogate
      markers did not abolish the strong association between PIs and increase in serum
      lipid levels. CONCLUSION: We found an independent association between PI use and
      hyperglycemia, hyperlipidemia, and lipodystrophy that is not explained by the
      antiviral and therapeutic effect of PIs.

PMID- 10888980
TI  - Cocaine and Buerger disease: is there a pathogenetic association?
AB  - A patient with a diagnosis of Buerger disease is described with peripheral limb
      ischemia and toe amputations, 2 recent small myocardial infarctions, and a long
      history of cigarette use. Peripheral angiography findings were incompatible with
      the clinical impression, and further workup revealed heavy recreational use of
      cocaine. A literature review of the clinical and pathologic manifestations of
      Buerger disease and of cocaine exposure shows them to have remarkable
      similarities. Based on our case observation and suggestive evidence from the
      literature, we propose that cocaine exposure may masquerade as Buerger disease,
      and further, that unrecognized cocaine exposure may underlie such cases, even
      including those originally described by Buerger in 1908.

PMID- 10888981
TI  - Food cobalamin malabsorption: a usual cause of vitamin B12 deficiency.

PMID- 10888983
TI  - Continued dependence on nicotine replacement therapy should be reported and
      discussed in smoking cessation trials.

PMID- 10888985
TI  - The need for improving information systems on drug interactions in Japan.

PMID- 10888987
TI  - Testosterone and cardiovascular risk factors.

PMID- 10888989
TI  - Is there enough evidence that low-molecular-weight heparin is superior to
      unfractionated heparin in pulmonary embolism?

PMID- 10888991
TI  - Interleukin 6 may be an important mediator of trimethoprim-induced systemic
      adverse reaction resembling aseptic meningitis.

PMID- 10888993
TI  - Gastropharyngeal and gastroesophageal reflux in globus and hoarseness.
AB  - BACKGROUND: The role of gastropharyngeal reflux in patients with globus
      pharyngeus and hoarseness remains unclear. OBJECTIVE: To evaluate patients with
      complaints of globus, hoarseness, or globus and hoarseness combined for the
      presence of gastropharyngeal and gastroesophageal reflux. DESIGN: Prospective
      clinical cohort study of 3 groups of patients undergoing ambulatory 24-hour
      double-probe pH monitoring. In patients with pathologic gastroesophageal reflux,
      an upper gastrointestinal endoscopy was also performed. SETTING: Tertiary care,
      outpatient clinic. PATIENTS: Twenty-seven patients with globus alone, 20 patients
      with hoarseness alone, and 25 patients with globus and hoarseness combined.
      RESULTS: Patients with well-defined pathologic reflux (ie, gastroesophageal
      reflux with or without gastropharyngeal reflux) were present mainly in the group
      of patients with globus combined with hoarseness: 18 (72%) of 25 patients,
      compared with 7 (35%) of 20 patients with hoarseness alone and 8 (30%) of 27 with
      globus alone. Seven (10%) of all 72 patients had prolonged acid exposure at the
      laryngopharyngeal junction in the presence of a normal gastroesophageal pH
      registration. Abnormal findings in the esophagus were found at endoscopy in 17
      (65%) of 26 patients with pathologic gastroesophageal reflux (with or without
      gastropharyngeal reflux). CONCLUSIONS: We found a high prevalence of pathologic
      reflux in patients with both globus and hoarseness. Based on these findings, we
      strongly advise upper gastrointestinal endoscopy for symptomatic
      otolaryngological patients with pathologic gastroesophageal reflux.

PMID- 10888994
TI  - Gastroesophageal reflux contributing to chronic sinus disease in children: a
      prospective analysis.
AB  - OBJECTIVE: To explore the possible role of gastroesophageal reflux (GER) in
      children with chronic sinus disease (CSD). DESIGN: A descriptive prevalence study
      of the frequency of GER and nasopharyngeal reflux in children with CSD. SETTING:
      Pediatric otolaryngology and gastroenterology outpatient clinics of a regional
      medical center. PATIENTS AND OTHER PARTICIPANTS: Consecutive children aged 2 to
      18 years referred for evaluation of CSD from December 1, 1996, through April 30,
      1998. INTERVENTIONS: Participants underwent 24-hour monitoring with dual pH
      probes, and participants (or their parents) completed questionnaires before
      treatment and at specific intervals after treatment. MAIN OUTCOME MEASURES:
      Prevalence of GER and nasopharyngeal reflux in children with CSD, and the
      response of sinusitis to treatment in those diagnosed with GER. RESULTS: Nineteen
      (63%) of 30 patients demonstrated esophageal reflux, which is well above the
      expected prevalence of GER in the healthy general population. Six (32%) of these
      19 patients demonstrated nasopharyngeal reflux. Fifteen (79%) of 19 patients
      improved after treatment for GER. CONCLUSIONS: The children in this population
      had a prevalence of GER that was significantly higher than expected. Furthermore,
      most children with GER demonstrated improvement of sinus disease after treatment
      of GER. We recommend that children with CSD refractory to aggressive medical
      management be evaluated for GER and, if GER is present, be treated accordingly,
      before sinus surgery is considered.

PMID- 10888995
TI  - Postoperative tonsillectomy pain in pediatric patients: electrocautery (hot) vs
      cold dissection and snare tonsillectomy--a randomized trial.
AB  - OBJECTIVE: To determine the effect of the method of tonsillectomy on
      postoperative pain in pediatric patients. DESIGN: Prospective, randomized, single
      blind, controlled clinical trial. SETTING: A university pediatric hospital in
      Aberdeen, Scotland. PATIENTS: A volunteer sample of 54 children, aged 3 to 12
      years, with recurrent tonsillitis or symptomatic adenotonsillar hypertrophy. Two
      patients withdrew consent. INTERVENTIONS: Twenty-six children underwent a
      nonelectrical (ie, cold) dissection tonsillectomy with cold steel instruments, 5
      of whom also had adenoidectomy by curettage. Monopolar diathermy forceps were
      used for tonsillar bed hemostasis. Twenty-four children had electrocautery (ie,
      hot) dissection tonsillectomy, 7 of whom underwent adenoidectomy by curettage
      without a suction coagulator. MAIN OUTCOME MEASURES: Postoperative analgesic
      consumption, time to regain normal diet and activity levels, and complications.
      RESULTS: Patients who underwent hot dissection tonsillectomy showed no difference
      in time to first drink or analgesic use within the first 24 postoperative hours
      compared with children undergoing cold nonelectrical dissection tonsillectomy.
      The hot dissection tonsillectomy group took 7.5 (95% confidence interval [CI], 1
      14.1) more doses of analgesics than the cold dissection group over the next 12
      days (P<.05). The hot dissection tonsillectomy group took 2.5 more days than the
      cold dissection tonsillectomy group to regain normal diet (P<.05). Thirteen
      children (54%; 95% CI, 34-74) in the hot dissection tonsillectomy group and 6
      (23%; 95% CI, 7-39) in the cold dissection tonsillectomy group sought outpatient
      care for throat pain, otalgia, poor diet, pyrexia, and/or bleeding (P<.05).
      Throat pain delayed in onset or of prolonged duration affected 9 children (38%;
      95% CI, 19-57) in the hot dissection tonsillectomy group as opposed to 3 children
      (12%; 95% CI, 0-24) in the cold dissection tonsillectomy group (P<.05).
      CONCLUSION: Hot dissection tonsillectomy increases morbidity in pediatric
      patients in the recovery period following hospital discharge.

PMID- 10888997
TI  - Age-related changes in muscle fiber regeneration in the human thyroarytenoid
      muscle.
AB  - BACKGROUND: Muscle fiber regeneration is essential to maintain normal muscle
      fiber populations and muscle mass by continuous replacement of fibers lost to
      acute muscle injury or overuse. However, the extent of ongoing muscle fiber
      regeneration in the laryngeal muscles is unknown. OBJECTIVE: The present study
      provides statistically unbiased, quantitative estimates of the content of
      regenerating fibers in the human thyroarytenoid muscle over the adult lifespan.
      DESIGN: In the adult, only regenerating muscle fibers express the developmental
      myosin isoform. Therefore, regenerating fibers were identified using
      immunohistochemical techniques. The content of regenerating muscle fibers in the
      entire muscle volume was then estimated using stereological techniques. Through
      the use of a computer-automated sampling protocol, stereological data were
      collected from sets of isotropic uniform random cryostat sections. Overprojection
      error was minimized by using a confocal laser-scanning microscope to image thin
      optical sections for use as sample fields. SUBJECTS: Eight autopsy cases,
      subjects ranging in age from 19 to 81 years. RESULTS: The summed length of fibers
      expressing developmental myosin increased significantly (P=.02) with age when
      compared with the overall muscle fiber length. CONCLUSIONS: This finding
      indicates that muscle fibers maintain the capability for spontaneous
      regeneration, and that the proportion of regenerating fibers increases as the
      thyroarytenoid muscle ages. This increase is possibly a compensatory response to
      an age-related increase in muscle fiber injury or death.

PMID- 10888996
TI  - Comparison of power-assisted adenoidectomy vs adenoid curette adenoidectomy.
AB  - OBJECTIVE: To compare the safety and efficacy of power-assisted adenoidectomy
      (PAA) vs adenoid curette adenoidectomy (ACA). DESIGN: A prospective randomized
      study. SETTING: Children's hospital of a tertiary care medical center. PATIENTS:
      Ninety patients (aged 1-13 years) underwent PAA, and 87 patients (aged 1-12
      years) underwent ACA. MAIN OUTCOME MEASURES: The parameters evaluated were
      operative time, blood loss, completeness and depth of resection, injuries to
      surrounding structures, short- and long-term complications, surgeon satisfaction
      with the procedure, and parents' assessment of the patient's postoperative
      recovery period. RESULTS: The PAA was 20% faster (P<.001) and had 27% less blood
      loss (P<.001) than the ACA. It provided a more complete resection(P<.001) and
      better control of the depth of resection (P<.05). Surgeon satisfaction was
      greater with PAA (P<.001). There was no difference in the recovery period or
      parent satisfaction. One patient in the PAA group returned to the operating room
      for control of postoperative bleeding, and 1 child in the ACA group returned to
      the hospital for postoperative dehydration. CONCLUSION: The PAA provides a
      faster, dryer, more complete, and more surgically satisfying resection than the
      ACA.

PMID- 10888998
TI  - New perspectives about human laryngeal muscle: single-fiber analyses and
      interspecies comparisons.
AB  - BACKGROUND: In companion studies on canine and rodent laryngeal muscle, we
      observed that (1) muscle fibers in both the canine and rodent posterior
      cricoarytenoid (PCA) muscles have a slower myosin heavy-chain (MyHC) isoform
      profile than those in the thyroarytenoid (TA) muscle; (2) the muscle fiber
      composition of PCA and TA muscles in canines and rodents is complex given the
      presence of so-called hybrid fibers (fibers coexpressing various combinations of
      MyHC isoforms); (3) the types and proportions of hybrid fibers are both muscle
      specific and, in some cases, region specific; and (4) the MyHC isoform profile of
      canine laryngeal muscle appears to be slower than that of rodent laryngeal
      muscle, suggesting the possibility that larger mammals have a slower MyHC isoform
      profile. OBJECTIVES: Given the findings of these companion studies and the fact
      that very little is known about the MyHC isoform composition of laryngeal muscle
      fibers, the primary objectives of this study were to determine (1) the types of
      MyHC isoforms found in the human PCA and TA muscles, (2) if there were regional
      differences in MyHC isoform composition, (3) if hybrid fibers commonly occur in
      human laryngeal muscle, and (4) if the MyHC isoform profile of human laryngeal
      muscle is slower than that of canine and rodent laryngeal muscle. RESULTS AND
      CONCLUSIONS: The findings of this study clearly demonstrate that both the PCA and
      TA muscles in humans express 3 types of MyHC isoforms (ie, slow type I, fast type
      IIA, and fast type IIX MyHC isoforms). At the single-fiber level, there were
      distinct regional differences and hybrid fibers were a common occurrence.
      Finally, the data demonstrate that the PCA and TA muscles of humans have a slower
      MyHC profile than that found in either canine or rodent laryngeal muscle.

PMID- 10888999
TI  - Are hybrid fibers a common motif of canine laryngeal muscles? Single-fiber
      analyses of myosin heavy-chain isoform composition.
AB  - BACKGROUND: The canine lateral cricoarytenoid muscle contains a large proportion
      of muscle fibers that coexpress various combinations of myosin heavy-chain
      isoforms (ie, so-called hybrid fibers). OBJECTIVE: To test the hypothesis that
      hybrid fibers are a common motif throughout laryngeal muscles. DESIGN: The
      posterior cricoarytenoid, canine cricothyroid, and thyroarytenoid muscles were
      removed from 5 beagle dogs. The posterior cricoarytenoid and canine cricothyroid
      muscles were each dissected into horizontal, oblique, and rectus regions. The
      thyroarytenoid was separated into medial and lateral regions. Approximately 40
      single fibers were microdissected from each region ( approximately 1800 total
      fibers were sampled) and placed into a denaturing sample buffer. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis was then used to separate the
      individual myosin heavy-chain isoforms. RESULTS: Each laryngeal muscle contained
      hybrid fibers; however, the types and proportions of hybrid fibers were clearly
      muscle specific. Within a given muscle, there were relatively minor regional
      differences in the types and proportions of hybrid fibers. CONCLUSION: If the
      myosin heavy-chain isoform composition of a single fiber can be used as a
      "physiological marker," then the extent of hybridism may reveal the diversity of
      activity required of a given laryngeal muscle.

PMID- 10889000
TI  - Single-fiber myosin heavy-chain isoform composition of rodent laryngeal muscle:
      modulation by thyroid hormone.
AB  - BACKGROUND: Studies have shown that canine laryngeal muscle contains a large
      number of muscle fibers that coexpress varying combinations of myosin heavy-chain
      (MyHC) isoforms. Currently, it is not clear whether this phenomenon is unique to
      canine laryngeal muscle or occurs in all mammals. OBJECTIVES: To examine the
      single-fiber MyHC isoform composition of rodent laryngeal muscle and to examine
      the plasticity of single-fiber MyHC isoform composition via manipulation of
      thyroid state. RESULTS: (1) Findings of single-fiber electrophoretic analyses
      clearly demonstrate that most fibers in both the posterior cricoarytenoid and
      thyroarytenoid muscles exhibit MyHC polymorphism. However, the proportions and
      patterns of polymorphism appear to be muscle specific. (2) Although the fast type
      IIL isoform was observed in fibers from both muscles, it was always coexpressed
      in combination with other MyHC isoforms (ie, no pure type IIL fibers were found),
      and always represented a minor proportion of the total MyHC pool. (3) Altering
      the thyroid state proved a useful tool for exploring the scope of MyHC isoform
      expression in these muscles. While the posterior cricoarytenoid muscle seemed
      more sensitive to the thyroid state, transitions in both muscles were primarily
      confined to the fast type IIX and IIB MyHC isoforms. CONCLUSION: The findings of
      this study support the concept that single-fiber MyHC polymorphism occurs
      commonly in mammalian laryngeal muscle.

PMID- 10889001
TI  - Development of the vestibular disorders activities of daily living scale.
AB  - BACKGROUND: Existing scales of self-perceived disablement in patients with
      vestibular impairment either are too broad to detect the subtle deficits in this
      population or omit some important daily life tasks. OBJECTIVES: To develop a
      scale to assess self-perceived disablement in patients with vestibular impairment
      and to describe the development and initial testing of this new assessment tool.
      DESIGN: A list of items was developed, sent to a panel of expert therapists for
      review, and then revised to yield the preliminary 31-item, 10-point scale that
      was administered to subjects. The scale was revised again, yielding the final 28
      item scale, which was administered to a new group of subjects. SETTING: Data were
      collected from patients in an outpatient clinic of a tertiary care center.
      PARTICIPANTS: Patients diagnosed as having benign paroxysmal positional vertigo
      and patients diagnosed as having chronic vestibulopathy, excluding Meniere
      disease, postsurgical vertigo, and postconcussion vertigo. RESULTS: The final
      scale has 3 subscales: functional, ambulation, and instrumental. It has good face
      validity, high internal consistency (alpha> or =.90), and high test-retest
      reliability (r(c)> or =0.87). Scale ratings ranged from 1 (independent) to 10
      (ceasing to participate in the activity), but median scores for most subjects
      were 4 or less. From 41% (39/94) to 44% (41/94) of subjects considered themselves
      to be independent on those tasks. CONCLUSIONS: This scale has good face validity,
      high internal consistency, and high test-retest reliability. It may be useful for
      evaluating functional limitation and perceived handicap or disability before and
      after intervention and for helping patients become more realistic in
      understanding their own capabilities.

PMID- 10889002
TI  - Management of auricular hematoma using a thermoplastic splint.
AB  - Several methods have been described in the literature for the management of acute
      auricular hematoma. Herein, we review the pathogenesis of auricular hematoma,
      describe the various treatment modalities, and report a case in which a
      thermoplastic splint was used to prevent recurrence of hematoma in a patient with
      immune thrombocytopenic purpura.

PMID- 10889003
TI  - Audiovestibular phenotype associated with a COL11A1 mutation in Marshall
      syndrome.
AB  - BACKGROUND: Marshall syndrome is a dominant disorder characterized by
      craniofacial and skeletal abnormalities, sensorineural hearing loss, myopia, and
      cataracts, and is associated with splicing mutations in COL11A1. OBJECTIVE: To
      determine the auditory and vestibular phenotypes associated with a COL11A1
      splicing. DESIGN: Clinical otolaryngologic, audiologic, vestibular, and
      radiologic evaluations of the auditory and vestibular systems. SUBJECTS: Three
      affected individuals from a family cosegregating Marshall syndrome and a COL11A1
      splice site mutation. RESULTS: The study subjects have progressive sensorineural
      hearing loss that is predominantly cochlear in origin and asymptomatic
      dysfunction of the central and peripheral vestibular systems. Computed tomography
      detected no malformations of temporal bone structures. CONCLUSIONS: The observed
      auditory and vestibular abnormalities are not caused by defective morphogenesis
      of the osseous labyrinth, but by more direct effects of the COL11A1 mutation on
      the membranous labyrinth and the central nervous system. The onset and degree of
      hearing loss associated with COL11A1 mutations are useful clinical features to
      differentiate Marshall syndrome from the phenotypically similar Stickler
      syndrome.

PMID- 10889004
TI  - Osteoma of the internal auditory canal.
AB  - OBJECTIVE: To review presenting symptoms and illustrate management options for
      this uncommon lesion. DESIGN: Case series and literature review. SETTING:
      Tertiary referral center. PATIENTS: Three cases of osteoma of the internal
      auditory canal are presented. Additional cases from the literature, diagnosed by
      radiographic appearance or gross description, are included for comparison. MAIN
      OUTCOME MEASURE: Response of clinical symptoms. RESULTS: Presenting symptoms are
      highly variable. Available reports do not adequately define the natural history
      of the lesion. CONCLUSION: The lack of a consistent presentation despite a
      similar radiographic appearance suggests that the osteoma is often an incidental
      finding.

PMID- 10889005
TI  - Pathology forum: quiz case 1. Diagnosis: inflammatory myofibroblastic tumor
      (IMT).

PMID- 10889006
TI  - Pathology forum: quiz case 2. Diagnosis: fibromatosis.

PMID- 10889007
TI  - Pathology forum: quiz case 3. Diagnosis: cavernous hemangioma of the nasal bones.

PMID- 10889008
TI  - Pathology forum: quiz case 4. Diagnosis: synovial chondromatosis of the TMJ.

PMID- 10889009
TI  - Reconstruction of soft tissue defects in the oral cavity and oropharynx.

PMID- 10889010
TI  - Changing concepts in soft tissue repair of oral and oropharyngeal defects.

PMID- 10889011
TI  - All patients should be considered possible candidates for reconstruction with
      free flaps.

PMID- 10889012
TI  - Welcome to ARCHIVES CME

PMID- 10889013
TI  - Blocking lupus autoantibodies.

PMID- 10889014
TI  - Haplotyping by atomic force microscopy.

PMID- 10889015
TI  - Technical Reports.

PMID- 10889016
TI  - Contribution of enzyme-phosphoribosyl contacts to catalysis by orotidine 5'
      phosphate decarboxylase.
AB  - The crystal structure of the complex formed between recombinant yeast orotidine
      5'-phosphate decarboxylase and the competitive inhibitor 6-hydroxyuridine 5'
      phosphate reveals the presence of four hydrogen bonds between active site
      residues Tyr-217 and Arg-235 and the phosphoryl group of this inhibitor. When Tyr
      217 and Arg-235 are individually mutated to alanine, values of k(cat)/K(m) are
      reduced by factors of 3000- and 7300-fold, respectively. In the Y217A/R235A
      double mutant, activity is reduced more than 10(7)-fold. Experiments with highly
      enriched [(14)C]orotic acid show that when ribose 5'-phosphate is deleted from
      substrate orotidine 5'-phosphate, k(cat)/K(m) is reduced by more than 12 orders
      of magnitude, from 6.3 x 10(7) M(-1) s(-1) for OMP to less than 2.5 x 10(-5) M(
      1) s(-1) for orotic acid. Activity toward orotate is not "rescued" by 1 M
      inorganic phosphate. The K(i) value of ribose 5'-phosphate, representing the part
      of the natural substrate that is absent in orotic acid, is 8.1 x 10(-5) M. Thus,
      the effective concentration of the 5'-phosphoribosyl group, in stabilizing the
      transition state for enzymatic decarboxylation of OMP, is estimated to be >2 x
      10(8) M, representing one of the largest connectivity effects that has been
      reported for an enzyme reaction.

PMID- 10889017
TI  - Chemical activity of cholesterol in membranes.
AB  - Measurements are reported for the rate constants for the release of cholesterol
      (and dihydrocholesterol) to beta-cyclodextrin from mixtures with phospholipids in
      homogeneous monolayers at constant pressure at the air-water interface. In each
      mixture, it is found that the release rate shows a sharp decrease as the
      cholesterol concentration in the monolayer decreases through a composition
      corresponding to the stoichiometry of a cholesterol-phospholipid complex. The
      stoichiometry of the complex was established previously by the position of a
      sharp cusp in the thermodynamic phase diagram of each mixture and also by a
      minimum in average molecular area versus composition measurements. A theoretical
      model used earlier to account for the phase diagrams predicts the chemical
      potential and chemical activity of cholesterol in these mixtures. The calculated
      chemical activity also shows a sharp change at the complex stoichiometry in
      homogeneous monolayers. The similarities in change of observed release rate and
      calculated chemical activity are expected from reaction rate theory where the
      release rate is proportional to the cholesterol chemical activity. The chemical
      activity of cholesterol as determined by complex formation between some
      phospholipids and cholesterol in the plasma membrane of cells may serve a
      regulatory function with respect to intracellular cholesterol transport and
      biosynthesis.

PMID- 10889018
TI  - Copper(2+) binding to the surface residue cysteine 111 of His46Arg human copper
      zinc superoxide dismutase, a familial amyotrophic lateral sclerosis mutant.
AB  - Mutations in copper-zinc superoxide dismutase (CuZnSOD) cause 25% of familial
      amyotrophic lateral sclerosis (FALS) cases. This paper examines one such mutant,
      H46R, which has no superoxide dismutase activity yet presumably retains the gain
      of-function activity that leads to disease. We demonstrate that Cu(2+) does not
      bind to the copper-specific catalytic site of H46R CuZnSOD and that Cu(2+)
      competes with other metals for the zinc binding site. Most importantly, Cu(2+)
      was found to bind strongly to a surface residue near the dimer interface of H46R
      CuZnSOD. Cysteine was identified as the new binding site on the basis of multiple
      criteria including UV-vis spectroscopy, RR spectroscopy, and chemical
      derivatization. Cysteine 111 was pinpointed as the position of the reactive
      ligand by tryptic digestion of the modified protein and by mutational analysis.
      This solvent-exposed residue may play a role in the toxicity of this and other
      FALS CuZnSOD mutations. Furthermore, we propose that the two cysteine 111
      residues, found on opposing subunits of the same dimeric enzyme, may provide a
      docking location for initial metal insertion during biosynthesis of wild-type
      CuZnSOD in vivo.

PMID- 10889019
TI  - Multiple interactions of the Asp(2.61(98)) side chain of the gonadotropin
      releasing hormone receptor contribute differentially to ligand interaction.
AB  - Mutation of Asp(2.61(98)) at the extracellular boundary of transmembrane helix 2
      of the gonadotropin-releasing hormone (GnRH) receptor decreased the affinity for
      GnRH. Using site-directed mutagenesis, ligand modification, and computational
      modeling, different side chain interactions of Asp(2.61(98)) that contribute to
      high-affinity binding were investigated. The conservative Asp(2. 61(98))Glu
      mutation markedly decreased the affinity for a series of GnRH analogues
      containing the native His(2) residue. This mutant showed smaller decreases in
      affinity for His(2)-substituted ligands. The loss of preference for His(2)
      containing ligands in the mutant receptor shows that Asp(2.61(98)) determines the
      specificity for His(2). Analysis of the affinities of a series of position 2
      substituted ligands suggests that a hydrogen bond forms between Asp(2.61(98)) and
      the delta NH group of His(2) and that Asp(2. 61(98)) forms a second hydrogen bond
      with the ligand. Substitution of Asp(2.61(98)) with an uncharged residue further
      decreased the affinity for all ligands and also decreased receptor expression.
      Computational modeling indicates an intramolecular ionic interaction of
      Asp(2.61(98)) with Lys(3.32(121)) in transmembrane helix 3. The uncharged,
      Lys(3.32(121))Gln mutation also markedly decreased agonist affinity. The modeling
      and the similar phenotypes of mutants with uncharged substitutions for
      Asp(2.61(98)) or Lys(3.32(121)) are consistent with the presence of this helix 2
      helix 3 interaction. These studies support a dual role for Asp(2.61(98)):
      formation of an interhelical interaction with Lys(3.32(121)) that contributes to
      the structure of the agonist binding pocket and an interaction with His(2) of
      GnRH that helps stabilize agonist complexing.

PMID- 10889020
TI  - Mapping the bimolecular interface of the parathyroid hormone (PTH)-PTH1 receptor
      complex: spatial proximity between Lys(27) (of the hormone principal binding
      domain) and leu(261) (of the first extracellular loop) of the human PTH1
      receptor.
AB  - In an effort to characterize the bimolecular interface between parathyroid
      hormone (PTH) and its human receptor PTH1-Rc (hPTH1-Rc), we previously identified
      two contact sites in the receptor: one for position 1 and another for position 13
      (located at the ends of the principal activation domain) in PTH(1-34). The
      present study reports a third, novel "contact site" between hPTH1-Rc and Lys(27)
      of PTH(1-34). Lys(27) is located in the principal binding domain of the hormone
      (residues 25-34). The photoreactive PTH(1-34) analogue K27 contains a
      benzophenone (BP) moiety on Lys(27). The analogue binds to stably transfected HEK
      293/C-21 cells (which express a high level of recombinant hPTH1-Rc) and
      stimulates adenylyl cyclase activity with a potency similar to PTH(1-34). In
      addition, (125)I-K27 cross-links effectively and specifically to the hPTH1-Rc.
      Enzymatic (Glu-C and Lys-C) and chemical (CNBr and BNPS-skatole) digestions of
      the photoconjugate between (125)I-K27 and hPTH1-Rc were performed. In addition,
      photoconjugates involving the bioactive mutants [L261M]- and [R262K]-hPTH1-Rc,
      transiently expressed in COS-7 cells, were also digested. The data obtained
      clearly identify L(261) or R(262) of the first extracellular loop of hPTH1-Rc as
      the contact site for Lys(27) in the hormone. On the basis of (i) the similarity
      in molecular mass between the CNBr digest of the (125)I-K27-[L261M]hPTH1-Rc
      conjugate and free (125)I-K27 and (ii) the failure to cross-link (125)I-K27 to a
      bioactive mutant receptor [L261A]hPTH1-Rc, we conclude that L(261) is the cross
      linking site. These results provide the first demonstration of an interaction
      between the principal binding domain of PTH and the first extracellular loop of
      hPTH1-Rc. Revealing proximity of Lys(27) (in PTH) to L(261) (in hPTH1-Rc)
      provides additional insight into the nature of the ligand-receptor bimolecular
      interface and clearly illustrates that the extracellular loops of the receptor
      contribute to the specificity of the PTH-PTH1-Rc interaction. Taken together with
      previous studies, the new findings add important constraints on the possible
      positioning of the C-terminal helix of PTH (which contains the principal binding
      domain) relative to the first extracellular loop and the distal C-terminal helix
      of the large extracellular amino terminal domain of the PTH1-Rc.

PMID- 10889021
TI  - Characterization of parathyroid hormone/receptor interactions: structure of the
      first extracellular loop.
AB  - The structural features of the first extracellular loop (ECL1) of the parathyroid
      hormone receptor (PTH1R) in the presence of dodecylphosphocholine micelles have
      been determined using high-resolution NMR techniques. The structure of the
      receptor fragment, PTH1R(241-285), includes three alpha-helices for residues 241
      244, 256-264, and 275-284. The first and third correspond to the end and the
      beginning of transmembrane helices 2 and 3, respectively. Centrally located in
      the second helix is L(261), found to cross-link to Lys(27) of parathyroid
      hormone, PTH(1-34) [Greenberg, Z., Bisello, A., Mierke, D. F., Rosenblatt, M.,
      and Chorev, M. (2000) Biochemistry 39, 8142-8152]. On the basis of nitroxide
      radical-induced relaxation studies, the central helix is found to associate with
      the surface of the membrane mimetic. These data, in conjunction with previous
      results indicating a preference of PTH for the lipid surface, suggest a membrane
      associated pathway for the initial recognition and binding of PTH to its G
      protein-coupled receptor. Using the structural features of ECL1 as determined
      here, along with the structure of the PTH(1-34), the intermolecular interactions
      consistent with the contact point between L(261)(receptor)-Lys(27)(ligand) are
      identified.

PMID- 10889022
TI  - KcsA crystal structure as framework for a molecular model of the Na(+) channel
      pore.
AB  - The crystal structure of the pore-forming part of the KcsA bacterial K(+)
      selective channel suggests a possible motif for related voltage-gated channels.
      We examined the hypothesis that the spacial orientation of the KcsA M1 and M2
      alpha-helices also predicts the backbone location of S5 and S6 helices of the
      voltage-gated Na(+) channel. That channel's P region structure is expected to be
      different because selectivity is determined by side-chain interactions rather
      than by main-chain carbonyls, and its outer vestibule accommodates relatively
      large toxin molecules, tetrodotoxin (TTX) and saxitoxin (STX), which interact
      with selectivity ring residues. The Na(+) channel P loop was well-modeled by the
      alpha-helix-turn-beta-strand motif, which preserves the relationships for toxin
      interaction with the Na(+) channel found experimentally. This outer vestibule was
      docked into the extracellular part of the inverted teepee structure formed by the
      S5 and S6 helices that were spacially located by coordinates of the KcsA M1 and
      M2 helix main chains [Doyle et al. (1998) Science 280, 69-74], but populated with
      side chains of the respective S5 and S6 structures. van der Waals contacts were
      optimized with minimal adjustment of the S5, S6, and P loop structures, forming a
      densely packed pore structure. Nonregular external S5-P and P-S6 segments were
      not modeled here, except the P-S6 segment of domain II. The resulting selectivity
      region structure is consistent with Na(+) channel permeation properties, offering
      suggestions for the molecular processes involved in selectivity. The ability to
      construct a Na(+) channel pore model consistent with most of the available
      biophysical and mutational information suggests that the KcsA structural
      framework may be conserved in voltage-gated channels.

PMID- 10889023
TI  - Structural basis of plasticity in protein tyrosine phosphatase 1B substrate
      recognition.
AB  - Protein tyrosine phosphatase 1B (PTP1B) displays a preference for peptides
      containing acidic as well as aromatic/aliphatic residues immediately NH(2)
      terminal to phosphotyrosine. The structure of PTP1B bound with DADEpYL-NH(2)
      (EGFR(988)(-)(993)) offers a structural explanation for PTP1B's preference for
      acidic residues [Jia, Z., Barford, D., Flint, A. J., and Tonks, N. K. (1995)
      Science 268, 1754-1758]. We report here the crystal structures of PTP1B in
      complex with Ac-ELEFpYMDYE-NH(2) (PTP1B.Con) and Ac-DAD(Bpa)pYLIPQQG (PTP1B.Bpa)
      determined to 1.8 and 1.9 A resolution, respectively. A structural analysis of
      PTP1B.Con and PTP1B.Bpa shows how aromatic/aliphatic residues at the -1 and -3
      positions of peptide substrates are accommodated by PTP1B. A comparison of the
      structures of PTP1B.Con and PTP1B.Bpa with that of PTP1B.EGFR(988)(-)(993)
      reveals the structural basis for the plasticity of PTP1B substrate recognition.
      PTP1B is able to bind phosphopeptides by utilizing common interactions involving
      the aromatic ring and phosphate moiety of phosphotyrosine itself, two conserved
      hydrogen bonds between the Asp48 carboxylate side chain and the main chain
      nitrogens of the pTyr and residue 1, and a third between the main chain nitrogen
      of Arg47 and the main chain carbonyl of residue -2. The ability of PTP1B to
      accommodate both acidic and hydrophobic residues immediately NH(2)-terminal to
      pTyr appears to be conferred upon PTP1B by a single residue, Arg47. Depending on
      the nature of the NH(2)-terminal amino acids, the side chain of Arg47 can adopt
      one of two different conformations, generating two sets of distinct peptide
      binding surfaces. When an acidic residue is positioned at position -1, a
      preference for a second acidic residue is also observed at position -2. However,
      when a large hydrophobic group occupies position -1, Arg47 adopts a new
      conformation so that it can participate in hydrophobic interactions with both
      positions -1 and -3.

PMID- 10889024
TI  - Errors from selective disruption of the editing center in a tRNA synthetase.
AB  - Some aminoacyl-tRNA synthetases have two catalytic centers that together achieve
      fine-structure discrimination of closely similar amino acids. The role of tRNA is
      to stimulate translocation of a misactivated amino acid from the active site to
      the editing site where the misactivated substrate is eliminated by hydrolysis.
      Using isoleucyl-tRNA synthetase as an example, we placed mutations in the
      catalytic center for editing at residues strongly conserved from bacteria to
      humans. A particular single substitution and one double substitution resulted in
      production of mischarged tRNA, by interfering specifically with the chemical step
      of hydrolytic editing. The substitutions affected neither amino acid activation
      nor aminoacylation, with the cognate amino acid. Thus, because of the
      demonstrated functional independence of the two catalytic sites, errors of
      aminoacylation can be generated by selective mutations in the center for editing.

PMID- 10889025
TI  - Exploring the role of glutamine 50 in the homeodomain-DNA interface: crystal
      structure of engrailed (Gln50 --> ala) complex at 2.0 A.
AB  - We have determined the crystal structure of a complex containing the engrailed
      homeodomain Gln50 --> Ala variant (QA50) bound to the wild-type optimal DNA site
      (TAATTA) at 2.0 A resolution. Biochemical and genetic studies by other groups
      have suggested that residue 50 is an important determinant of differential DNA
      binding specificity among homeodomains (distinguishing among various sites of the
      general form TAATNN). However, biochemical studies of the QA50 variant had
      revealed that it binds almost as tightly as the wild-type protein and with only
      modest changes in specificity. We have now determined the crystal structure of
      the QA50 variant to help understand the role of residue 50 in site-specific
      recognition. Our cocrystal structure shows some interesting changes in the water
      structure at the site of the substitution and shows some changes in the
      conformations of neighboring side chains. However, the structure, like the QA50
      biochemical data, suggests that Gln50 plays a relatively modest role in
      determining the affinity and specificity of the engrailed homeodomain.

PMID- 10889026
TI  - Metal interactions with a GAAA RNA tetraloop characterized by (31)P NMR and
      phosphorothioate substitutions.
AB  - A metal site in a 5'-GAAA-3' tetraloop, a stabilizing and phylogenetically
      conserved RNA motif, is explored using (31)P NMR spectroscopy and
      phosphorothioate modifications. Similar to previous reports [Legault, P., and
      Pardi, A. (1994) J. Magn. Reson., Ser. B 103, 82-86], the (31)P NMR spectrum of a
      12-nucleotide stem-loop sequence 5'-GGCCGAAAGGCC-3' exhibits resolved features
      from each of the phosphodiester linkages. Titration with Mg(2+) results in
      distinct shifts of a subset of these (31)P features, which are assigned to
      phosphodiesters 5' to A6, A7, and G5. Titration with Co(NH(3))(6)(3+) causes only
      a slight upfield shift in the A6 feature, suggesting that changes caused by
      Mg(2+) are due to inner-sphere metal-phosphate coordination. R(p)
      Phosphorothioate substitutions introduced enzymatically 5' to each of the three A
      residues of the tetraloop provide well-resolved (31)P NMR features that are
      observed to shift in the presence of Cd(2+) but not Mg(2+), again consistent with
      a metal-phosphate site. Analysis of (31)P NMR spectra using the sequence 5'
      GGGCGAAAGUCC-3' with single phosphorothioate substitutions in the loop region,
      separated into R(p) and S(p) diastereomers, provides evidence for an inner-sphere
      interaction with the phosphate 5' to A7 but outer-sphere or structural effects
      that cause perturbations 5' to A6. Introduction of an R(p)-phosphorothioate 5' to
      A7 results in a distinct (31)P NMR spectrum, consistent with thermodynamic
      studies reported in the accompanying paper that indicate a unique structure
      caused by this substitution. On the basis of these results and existing
      structural information, a metal site in the 5'-GAAA-3' tetraloop is modeled using
      restrained molecular dynamics simulations.

PMID- 10889027
TI  - Impact of phosphorothioate substitutions on the thermodynamic stability of an RNA
      GAAA tetraloop: an unexpected stabilization.
AB  - This study analyzes the impact of phosphorothioate substitutions on the
      thermodynamic stability of a 12-nt RNA hairpin containing a (5')GAAA(3')
      tetraloop. The thermodynamic consequences of stereospecific phosphorothioate
      substitutions 5' to each adenosine in the loop region are measured using optical
      melting and calorimetry experiments. Surprisingly, a single stereospecific
      phosphorothioate substitution 5' to the second adenosine of the tetraloop, R(p)
      A7, results in a stabilization corresponding to a Delta(DeltaG(37)(degrees)(C))
      of approximately -2.9 kcal mol(-1) (0.1 M NaCl) when compared with that of an
      unmodified sample. Five other phosphorothioate-substituted samples did not show
      significant thermodynamic differences in comparison with the unsubstituted
      samples. Addition of Mg(2+) to all of the hairpins studied results in increased
      t(m's) that are fit with a general electrostatic model to a dissociation constant
      of K(d)(Mg(2+)) approximately 2-3 mM (0.1 M NaCl). The R(p)-A7 phosphorothioate
      substituted hairpin showed an unusual decrease in t(m) and apparent increase in
      enthalpy of unfolding upon addition of Cd(2+). These results may impact the
      interpretation of interference mapping experiments that use phosphorothioate
      substitutions to characterize RNAs in solution.

PMID- 10889028
TI  - Recognition of alpha-amino acids bearing various C=NOH functions by nitric oxide
      synthase and arginase involves very different structural determinants.
AB  - Several alpha-amino acids bearing a C=NOH function separated from the Calpha
      carbon by two to five atoms have been synthesized and tested as substrates or
      inhibitors of recombinant nitric oxide synthases (NOS) I and II and as inhibitors
      of rat liver arginase (RLA). These include four N-hydroxyguanidines, N(omega)
      hydroxy-L-arginine (NOHA) and its analogues homo-NOHA, nor-NOHA, and dinor-NOHA,
      two amidoximes bearing the -NH-C(CH(3))=NOH group, and two amidoximes bearing the
      -CH(2)-C(NH(2))=NOH group. Their behavior toward NOS and RLA was compared to that
      of the corresponding compounds bearing a C=NH function instead of the C=NOH
      function. The results obtained clearly show that efficient recognition of these
      alpha-amino acids by NOS and RLA involves very different structural determinants.
      NOS favors molecules bearing a -NH-C(R)=NH motif separated from Calpha by three
      or four CH(2) groups, such as arginine itself, with the necessary presence of
      delta-NH and omega-NH groups and a more variable R substituent. The corresponding
      molecules with a C=NOH function exhibit a much lower affinity for NOS. On the
      contrary, RLA best recognizes molecules bearing a C=NOH function separated from
      Calpha by three or four atoms, the highest affinity being observed in the case of
      three atoms. The presence of two omega-nitrogen atoms is important for efficient
      recognition, as in the two best RLA inhibitors, N(omega)-hydroxynorarginine and
      N(omega)-hydroxynorindospicine, which exhibit IC(50) values at the micromolar
      level. However, contrary to what was observed in the case of NOS, the presence of
      a delta-NH group is not important. These different structural requirements of NOS
      and RLA may be directly linked to the position of crucial residues that have been
      identified from crystallographic data in the active sites of both enzymes. Thus,
      binding of arginine analogues to NOS particularly relies on strong interactions
      of their delta-NH and omega-NH(2) groups with glutamate 371 (of NOS II), whereas
      binding of C=NOH molecules to RLA is mainly based on interactions of their
      terminal OH group with the binuclear Mn(II).Mn(II) cluster of the enzyme and on
      possible additional bonds between their omega-NH(2) group with histidine 141,
      glutamate 277, and one Mn(II) ion. The different modes of interaction displayed
      by both enzymes depend on their different catalytic functions and give
      interesting opportunities to design useful molecules to selectively regulate NOS
      and arginase.

PMID- 10889029
TI  - Structure, dynamics, and insertion of a chloroplast targeting peptide in mixed
      micelles.
AB  - Nuclear-encoded, chloroplast-destined proteins are synthesized with transit
      sequences that contain all information to get them inside the organelle.
      Different proteins are imported via a general protein import machinery, but their
      transit sequences do not share amino acid homology. It has been suggested that
      interactions between transit sequence and chloroplast envelope membrane lipids
      give rise to recognizable, structural motifs. In this study a detailed
      investigation of the structural, dynamical, and topological features of an
      isolated transit peptide associated with mixed micelles is described. The
      structure of the preferredoxin transit peptide in these micelles was studied by
      circular dichroism (CD) and multidimensional NMR techniques. CD experiments
      indicated that the peptide, which is unstructured in aqueous solution, obtained
      helical structure in the presence of the micelles. By NMR it is shown that the
      micelles introduced ill-defined helical structures in the transit peptide.
      Heteronuclear relaxation experiments showed that the whole peptide backbone is
      very flexible. The least dynamic segments are two N- and C-terminal helical
      regions flanking an unstructured proline-rich amino acid stretch. Finally, the
      insertion of the peptide backbone in the hydrophobic interior of the micelle was
      investigated by use of hydrophobic spin-labels. The combined data result in a
      model of the transit peptide structure, backbone dynamics, and insertion upon its
      interaction with mixed micelles.

PMID- 10889030
TI  - Proton transfer limits protein translocation rate by the thylakoid DeltapH/Tat
      machinery.
AB  - The thylakoid transmembrane DeltapH is the sole energy source driving
      translocation of precursor proteins by the DeltapH/Tat machinery. Consequently,
      proton translocation must be coupled to precursor translocation. For the
      precursor of the 17 kDa protein of the oxygen-evolving complex (pOE17), the
      protein translocation process is characterized by a steep drop in efficiency at
      an external pH below 7.0 and above 8.7. As the membrane DeltapH is virtually
      unaffected from pH 6.5 to 9.2, the loss in import efficiency is a consequence of
      the titration of multiple residues within the translocation machinery. Transport
      is retarded by a factor of 2-3 in deuterium oxide (D(2)O) relative to water,
      strongly suggesting that proton-transfer reactions limit translocation rate. The
      solvent isotope effect manifests itself after the precursor binds to the
      membrane, indicating that the rate-limiting step is a later event in the
      transport process.

PMID- 10889031
TI  - Effect of pH on axial ligand coordination of cytochrome c" from Methylophilus
      methylotrophus and horse heart cytochrome c.
AB  - The effect of protons on the axial ligand coordination and on structural aspects
      of the protein moiety of cytochrome c' ' from Methylophilus methylotrophus, an
      obligate methylotroph, has been investigated down to very low pH (i.e., 0.3). The
      unusual resistance of this cytochrome to very low pH values has been exploited to
      carry out this study in comparison with horse heart cytochrome c. The experiments
      were undertaken at a constant phosphate concentration to minimize the variation
      of ionic strength with pH. The pH-linked effects have been monitored at 23
      degrees C in the oxidized forms of both cytochromes by following the variations
      in the electronic absorption, circular dichroism and resonance Raman spectra.
      This approach has enabled the conformational changes of the heme surroundings to
      be monitored and compared with the concomitant overall structural rearrangements
      of the molecule. The results indicate that horse heart cytochrome c undergoes a
      first conformational change at around pH 2.0. This event is possibly related to
      the cleavage of the Fe-Met80 bond and a likely coordination of a H(2)O molecule
      as a sixth axial ligand. Conversely, in cytochrome c" from M. methylotrophus, a
      variation of the axial ligand coordination occurs at a pH that is about 1 unit
      lower. Further, it appears that a concerted cleavage of both His ligands takes
      place, suggesting indeed that the different axial ligands present in horse heart
      cytochrome c (Met/His) and in cytochrome c" from M. methylotrophus (His/His)
      affect the heme conformational changes.

PMID- 10889032
TI  - Only a small fraction of purified hepatitis C RNA-dependent RNA polymerase is
      catalytically competent: implications for viral replication and in vitro assays.
AB  - The enzymatic activity of a C-terminally truncated form of the RNA-dependent RNA
      polymerase, termed NS5B(Delta21), of the hepatitis C virus (strain BK) has been
      investigated using both homopolymeric and heteropolymeric RNA templates.
      Incorporation of nucleotides into a heteropolymeric RNA template as catalyzed by
      NS5B(Delta21) is characterized by biphasic reaction time courses. At high
      concentrations of nucleoside triphosphate in reactions allowing a preincubation
      of NS5B(Delta21) and RNA template, an initial rapid phase of the reaction is
      followed by a slower linear phase. The amplitude of the first phase of the
      reaction varies directly with the concentration of the enzyme in the reaction. It
      is shown here that full-length copies of the template are produced during the
      first phase of the reaction. Our results reveal that NS5B(Delta21) is processive
      but only a small fraction, less than 1%, of the purified enzyme present
      participates productively in the reaction. Most importantly, the turnover number
      for the hepatitis C NS5B(Delta21) is comparable to those observed for other
      polymerases such as the HIV-1 reverse transcriptase. The combined results
      reconcile in part the apparent discrepancy of the low, observed specific activity
      of the purified enzyme and the rapid generation of HCV in vivo.

PMID- 10889033
TI  - Mapping contacts between Escherichia coli alanyl tRNA synthetase and 2' hydroxyls
      using a complete tRNA molecule.
AB  - A dual-specific derivative of yeast tRNA(Phe) is described whose features
      facilitate structure-function studies of tRNAs. This tRNA has been made in three
      different bimolecular forms that allow modifications to be easily introduced into
      any position within the molecule. A set of deoxynucleotide substituted versions
      of this tRNA has been created and used to examine contacts between tRNA and
      Escherichia coli alanyl-tRNA synthetase, an enzyme previously shown to interact
      with 2'-hydroxyls in the acceptor stem of the tRNA. Because the present
      experiments used a full-length tRNA, several contacts were identified that had
      not been previously found using microhelix substrates. Contacts at similar sites
      in the T-loop are seen in the cocrystal structure of tRNA(Ser) and Thermus
      thermophilus seryl-tRNA synthetase.

PMID- 10889034
TI  - Enhanced binding of the TATA-binding protein to TATA boxes containing flanking
      cisplatin 1,2-cross-links.
AB  - The TATA-binding protein (TBP) is essential for transcription initiation in
      eukaryotes. TBP recognizes and binds to the minor groove of a consensus sequence,
      TATAAA, known as the TATA box or TATA element. DNA binding is affected largely by
      hydrophobic contacts and through the intercalation of two sets of adjacent
      phenylalanine residues. The resultant duplex is sharply kinked, bending toward
      the major groove. Inspired by prior structural information showing intercalation
      of a phenylalanine side chain of a high mobility group (HMG) domain into the site
      of a cisplatin 1, 2-intrastrand d(GpG) cross-link, a series of DNA probes was
      prepared with one or two such adducts flanking the TATA box positions at or near
      the sites of TBP intercalation. The platinum adducts bend the DNA toward the
      major groove and result in as much as a 175-fold increase in binding affinity of
      the TBP over the unmodified target sequence. Kinetic studies indicate that the
      enhanced binding to the modified TATA box is predominantly a consequence of a >30
      fold slower dissociation rate of the protein-platinated DNA complex. This work
      demonstrates that it is feasible to design rationally and to synthesize an
      enhanced affinity-binding site for a sequence-specific DNA-binding protein by
      appropriate chemical modification of flanking sequences. It also has implications
      for the mechanism of action of cisplatin.

PMID- 10889036
TI  - Human apolipoprotein C-II forms twisted amyloid ribbons and closed loops.
AB  - Human apolipoprotein C-II (apoC-II) self-associates in solution to form
      aggregates with the characteristics of amyloid including red-green birefringence
      in the presence of Congo Red under cross-polarized light, increased fluorescence
      in the presence of thioflavin T, and a fibrous structure when examined by
      electron microscopy. ApoC-II was expressed and purified from Escherichia coli and
      rapidly exchanged from 5 M guanidine hydrochloride into 100 mM sodium phosphate,
      pH 7.4, to a final concentration of 0.3 mg/mL. This apoC-II was initially
      soluble, eluting as low molecular weight species in gel filtration experiments
      using Sephadex G-50. Circular dichroism (CD) spectroscopy indicated predominantly
      unordered structure. Upon incubation for 24 h, apoC-II self-associated into high
      molecular weight aggregates as indicated by elution in the void volume of a
      Sephadex G-50 column, by rapid sedimentation in an analytical ultracentrifuge,
      and by increased light scattering. CD spectroscopy indicated an increase in beta
      sheet content, while fluorescence emission spectroscopy of the single tryptophan
      revealed a blue shift and an increase in maximum intensity, suggesting
      repositioning of the tryptophan into a less polar environment. Electron
      microscopy of apoC-II aggregates revealed a novel looped-ribbon morphology (width
      12 nm) and several isolated closed loops. Like all of the conserved plasma
      apolipoproteins, apoC-II contains amphipathic helical regions that account for
      the increase in alpha-helix content on lipid binding. The increase in beta
      structure accompanying apoC-II fibril formation points to an alternative folding
      pathway and an in vitro system to explore the general tendency of apolipoproteins
      to form amyloid in vivo.

PMID- 10889035
TI  - Functional comparison of the NAD binding cleft of ADP-ribosylating toxins.
AB  - Although a common core structure forms the active site of ADP-ribosylating
      (ADPRT) toxins, the limited-sequence homology within this region suggests that
      different mechanisms are being used by toxins to perform their shared function.
      To explain differences in their mechanisms of NAD binding and hydrolysis, the
      functional interrelationship of residues predicted to perform similar functions
      in the beta3-strand of the NAD binding cleft of different ADPRT toxins was
      compared. Replacing Tyr54 in the A-subunit of diphtheria toxin (DTA) with a
      serine, its functional homologue in cholera toxin (CT), resulted in the loss of
      catalytic function but not NAD binding. The catalytic role of the aromatic
      portion of Tyr54 in the ADPRT reaction was confirmed by the ability of a Tyr54-to
      phenylalanine DTA mutant to retain ADPRT activity. In reciprocal studies,
      positioning a tyrosine in the beta3-strand of the A1-subunit of CT (CTA1) caused
      both loss of function and altered structure. The restricted flexibility of the
      CTA1 active site relative to function became evident upon the loss of ADPRT
      activity when a conservative Val60-to-leucine mutation was performed. We conclude
      from our studies that DT and CT maintain a similar mechanism of NAD binding but
      differ in their mechanisms of NAD hydrolysis. The aromatic moiety at position 54
      in DT is integral to NAD hydrolysis, while NAD hydrolysis in CT appears highly
      dependent on the precise positioning of specific residues within the beta3-strand
      of the active-site cleft.

PMID- 10889037
TI  - Altering the specificity of CooA, the carbon monoxide-sensing transcriptional
      activator: characterization of CooA variants that bind cyanide in the Fe(II) form
      with high affinity.
AB  - CooA is a carbon monoxide- (CO-) sensing homodimeric heme protein that activates
      the transcription of genes required for the anaerobic oxidation of CO to CO(2) in
      the phototrophic bacterium Rhodospirillum rubrum. In this study, we demonstrate
      that mutational alteration of the histidine residue (His(77)) that serves as a
      heme ligand in the Fe(II) form of CooA allows high-affinity binding of cyanide
      (K(d) approximately 0.4 mM) to the heme. In contrast, neither these same variants
      in the Fe(III) form nor wild-type CooA in either oxidation state was able to bind
      cyanide even at high concentrations (50 mM). Examination of the pH dependence of
      spectral changes upon addition of cyanide suggested that the cyanide anion
      coordinated the heme iron. In addition, the UV-visible absorption spectrum of
      H77Y Fe(II) CooA without added effectors is also pH-dependent, suggesting that an
      ionizable amino acid has become solvent-accessible in the absence of His(77).
      Finally, we demonstrate that the transcriptional activity of H77Y CooA shows a
      small (1.4-fold) increase in the presence of cyanide, suggesting that the binding
      of cyanide to this variant promotes the active conformation of H77Y CooA.

PMID- 10889038
TI  - Tropomyosin 3 increases striated muscle isoform diversity.
AB  - Tropomyosin (TM), a component of the thin filament of the sarcomere, is encoded
      by a four-member multigene family: alpha-TM, beta-TM, TPM 3, and TPM 4. The alpha
      TM, beta-TM, and TPM 3 genes each utilize an alternative splicing mechanism to
      encode a striated muscle isoform. Although the alpha-TM and beta-TM striated
      muscle isoforms are well characterized, relatively little is known about the TPM
      3 isoform. We cloned and sequenced the murine TPM 3 cDNA and found that it
      exhibits a 93% nucleotide homology and 99% amino acid homology to the human
      sequence. Results show that, unlike humans, TPM 3 is not expressed in any
      developmental stage of murine hearts. TPM 3 message is expressed in slow-twitch
      skeletal muscle but is not found in representative fast-twitch musculature. The
      soleus, a representative slow-twitch muscle, expresses transcript levels of 65%
      beta-TM, 15% alpha-TM, and 20% TPM 3, but the TPM 3 protein accounts for
      approximately 31% of the total striated tropomyosin in slow-twitch muscle. In
      fast-twitch muscle, alpha-TM comprises 71% of the total striated muscle TM
      protein, and beta-TM comprises 29%. The results demonstrate that a translational
      mechanism regulates the production of the TM proteins, with beta-TM message not
      being efficiently translated. The unique distribution pattern of TPM 3 adds to
      the diversity of the tropomyosin family and strongly suggests functional
      significance for the different striated muscle TM isoforms.

PMID- 10889039
TI  - Mutational and biochemical analysis of plasma membrane targeting mediated by the
      farnesylated, polybasic carboxy terminus of K-ras4B.
AB  - Mutational analysis and in vitro assays of membrane association have been
      combined to investigate the mechanism of plasma membrane targeting mediated by
      the farnesylated, polybasic carboxy-terminal sequence of K-ras4B in mammalian
      cells. Fluorescence-microscopic localization of chimeric proteins linking the
      enhanced green fluorescent protein (EGFP) to the K-ras4B carboxy-terminal
      sequence, or to variant forms of this sequence, reveals that the normal structure
      of this targeting motif can be greatly altered without compromising plasma
      membrane-targeting activity so long as an overall strongly polybasic/amphiphilic
      character is retained. An EGFP/K-ras4B(171-188) chimeric protein was readily
      abstracted from isolated cell membranes by negatively charged lipid vesicles, and
      this abstraction was markedly enhanced by the anionic lipid-binding agent
      neomycin. Our results strongly favor a mechanism in which at the plasma membrane
      the carboxy-terminal sequence of K-ras4B associates not with a classical specific
      proteinaceous receptor but rather with nonspecific but highly anionic 'sites'
      formed at least in part by the membrane lipid bilayer. Our findings also suggest
      that the recently demonstrated prenylation-dependent trafficking of immature
      forms of K-ras4B through the endoplasmic reticulum [Choy et al. (1999) Cell 98,
      69-80], while required for maturation of the protein, beyond this stage may not
      be essential to allow the ultimate delivery of the mature protein to the plasma
      membrane.

PMID- 10889040
TI  - Evidence for partial secondary structure formation in the transition state for
      arc repressor refolding and dimerization.
AB  - Structure formation and dimerization are concerted processes in the refolding of
      Arc repressor. The integrity of secondary structure in the transition state of
      Arc refolding has been investigated here by determining the changes in
      equilibrium stability and refolding/unfolding kinetics for a set of Ala --> Gly
      mutations at residues that are solvent-exposed in the native Arc dimer. At some
      sites, reduced stability was caused primarily by faster unfolding, indicating
      that secondary structure at these positions is largely absent in the transition
      state. However, most of the Ala --> Gly substitutions in the alpha-helices of Arc
      and a triple mutant in the beta-sheet also resulted in decreased refolding rates,
      in some cases, accounting for the major fraction of thermodynamic
      destabilization. Overall, these results suggest that some regions of native
      secondary structure are present but incompletely formed in the transition state
      of Arc refolding and dimerization. Consolidation of this secondary structure,
      like close packing of the hydrophobic core, seems to occur later in the folding
      process. On average, Phi(F) values for the Ala --> Gly mutations were
      significantly larger than Phi(F) values previously determined for alanine
      substitution mutants, suggesting that backbone interactions in the transition
      state may be stronger than side chain interactions. Mutations causing significant
      reductions in the Arc refolding rate were found to cluster in the central turn of
      alpha-helix A and in the first two turns of alpha-helix B. In the Arc dimer,
      these elements pack together in a compact structure, which might serve as nucleus
      for further folding.

PMID- 10889041
TI  - MDP-1: A novel eukaryotic magnesium-dependent phosphatase.
AB  - We report here the purification, cloning, expression, and characterization of a
      novel phosphatase, MDP-1. In the course of investigating the reported acid
      phosphatase activity of carbonic anhydrase III preparations, several discrete
      phosphatases were discerned. One of these, a magnesium-dependent species of 18.6
      kDa, was purified to homogeneity and yielded several peptide sequences from which
      the parent gene was identified by database searching. Although orthologous genes
      were identified in fungi and plants as well as mammalian species, there was no
      apparent homology to any known family of phosphatases. The enzyme was expressed
      in Escherichia coli with a fusion tag and purified by affinity methods. The
      recombinant enzyme showed magnesium-dependent acid phosphatase activity
      comparable to the originally isolated rabbit protein. The enzyme catalyzes the
      rapid hydrolysis of p-nitrophenyl phosphate, ribose-5-phosphate, and
      phosphotyrosine. The selectivity for phosphotyrosine over phosphoserine or
      phosphothreonine is considerable, but the enzyme did not show activity toward
      five phosphotyrosine-containing peptides. None of the various substrates assayed
      (including various nucleotide, sugar, amino acid and peptide phosphates,
      phosphoinositides, and phosphodiesters) exhibited K(M) values lower than 1 mM,
      and many showed negligible rates of hydrolysis. The enzyme is inhibited by
      vanadate and fluoride but not by azide, cyanide, calcium, lithium, or tartaric
      acid. Chemical labeling, refolding, dialysis, and mutagenesis experiments suggest
      that the enzymatic mechanism is not dependent on cysteine, histidine, or
      nonmagnesium metal ions. In recognition of these observations, the enzyme has
      been given the name magnesium-dependent phosphatase-1 (MDP-1).

PMID- 10889042
TI  - Serine-53 at the tip of the glycine-rich loop of cAMP-dependent protein kinase:
      role in catalysis, P-site specificity, and interaction with inhibitors.
AB  - The glycine-rich loop, one of the most important motifs in the conserved protein
      kinase catalytic core, embraces the entire nucleotide, is very mobile, and is
      exquisitely sensitive to what occupies the active site cleft. Of the three
      conserved glycines [G(50)TG(52)SFG(55) in cAMP-dependent protein kinase (cAPK)],
      Gly(52) is the most important for catalysis because it allows the backbone amide
      of Ser(53) at the tip of the loop to hydrogen bond to the gamma-phosphate of ATP
      [Grant, B. D. et al. (1998) Biochemistry 37, 7708]. The structural model of the
      catalytic subunit:ATP:PKI((5)(-)(24)) (heat-stable protein kinase inhibitor)
      ternary complex in the closed conformation suggests that Ser(53) also might be
      essential for stabilization of the peptide substrate-enzyme complex via a
      hydrogen bond between the P-site carbonyl in PKI and the Ser(53) side-chain
      hydroxyl [Bossemeyer, D. et al. (1993) EMBO J. 12, 849]. To address the
      importance of the Ser(53) side chain in catalysis, inhibition, and P-site
      specificity, Ser(53) was replaced with threonine, glycine, and proline. Removal
      of the side chain (i.e., mutation to glycine) had no effect on the steady-state
      phosphorylation of a peptide substrate (LRRASLG) or on the interaction with
      physiological inhibitors, including the type-I and -II regulatory subunits and
      PKI. However, this mutation did affect the P-site specificity; the glycine mutant
      can more readily phosphorylate a P-site threonine in a peptide substrate (5-6
      fold better than wild-type). The proline mutant is compromised catalytically with
      altered k(cat) and K(m) for both peptide and ATP and with altered sensitivity to
      both regulatory subunits and PKI. Steric constraints as well as restricted
      flexibility could account for these effects. These combined results demonstrate
      that while the backbone amide of Ser(53) may be required for efficient catalysis,
      the side chain is not.

PMID- 10889043
TI  - Differential in vivo modifications of the HMGI(Y) nonhistone chromatin proteins
      modulate nucleosome and DNA interactions.
AB  - The HMGI(Y) family of "high mobility group" nonhistone proteins are architectural
      transcription factors whose overexpression is highly correlated with both
      cancerous transformation and increased malignancy and metastatic potential of
      tumors in vivo. Here we report on the types of posttranslational modifications
      found in vivo on the HMG-I and HMG-Y proteins isolated from two human breast
      epithelial cell lines, MCF-7 and MCF-7/PKC-alpha, that represent different stages
      of neoplastic progression. The MCF-7 cell line exhibits many characteristics of
      normal breast epithelial cells and does not form tumors when injected into nude
      mice, whereas the MCF-7/PKC-alpha cell line, a derivative of MCF-7 that expresses
      a transgene coding for the enzyme protein kinase C-alpha (PKC-alpha), is both
      malignant and highly metastatic. Using MALDI mass spectrometry, we show that the
      HMG-Y protein is more highly modified than the HMG-I protein in both the MCF-7
      and the MCF-7/PKC-alpha cells. Significantly, the HMG-Y protein isolated from the
      highly metastatic MCF-7/PKC-alpha cells possesses a unique constellation of
      phosphorylations, methylations, and acetylations not found on the HMG-I protein
      isolated from either the MCF-7 or MCF-7/PKC-alpha cells. We further demonstrate
      that some of the same amino acid residues phosphorylated on recombinant HMGI(Y)
      proteins by purified PKC in vitro are also phosphorylated on the HMG-I(Y)
      proteins isolated from MCF-7/PKC-alpha cells, suggesting that PKC phosphorylates
      these proteins in vivo. Quantitative substrate binding analyses indicate that the
      biochemical modifications present on the HMG-I and HMG-Y proteins differentially
      influence the ability of these proteins to interact with both A.T-rich DNA
      substrates and nucleosome core particles in vitro, suggesting a similar
      modulation of such binding affinities in vivo. To our knowledge, this is the
      first demonstration of differences in the types of in vivo biochemical
      modifications found on the HMG-I and HMG-Y proteins in cells and also the first
      experimental evidence suggesting a possible linkage between such
      posttranslational modifications and the neoplastic potential of cells.

PMID- 10889044
TI  - Chromosome 7q: where autism meets language disorder?

PMID- 10889045
TI  - Repeat polymorphisms within gene regions: phenotypic and evolutionary
      implications.
AB  - We have developed an algorithm that predicted 11,265 potentially polymorphic
      tandem repeats within transcribed sequences. We estimate that 22% (2,207/9,717)
      of the annotated clusters within UniGene contain at least one potentially
      polymorphic locus. Our predictions were tested by allelotyping a panel of
      approximately 30 individuals for 5% of these regions, confirming polymorphism for
      more than half the loci tested. Our study indicates that tandem-repeat
      polymorphisms in genes are more common than is generally believed. Approximately
      8% of these loci are within coding sequences and, if polymorphic, would result in
      frameshifts. Our catalogue of putative polymorphic repeats within transcribed
      sequences comprises a large set of potentially phenotypic or disease-causing
      loci. In addition, from the anomalous character of the repetitive sequences
      within unannotated clusters, we also conclude that the UniGene cluster count
      substantially overestimates the number of genes in the human genome. We
      hypothesize that polymorphisms in repeated sequences occur with some baseline
      distribution, on the basis of repeat homogeneity, size, and sequence composition,
      and that deviations from that distribution are indicative of the nature of
      selection pressure at that locus. We find evidence of selective maintenance of
      the ability of some genes to respond very rapidly, perhaps even on
      intragenerational timescales, to fluctuating selective pressures.

PMID- 10889046
TI  - Autozygosity mapping of a seckel syndrome locus to chromosome 3q22. 1-q24.
AB  - Seckel syndrome (MIM 210600) is an autosomal recessive disorder of low birth
      weight, severe microcephaly, and dysmorphic facial appearance with receding
      forehead, prominent nose, and micrognathia. We have performed a genomic screen in
      two consanguineous families of Pakistani origin and found that the disorder
      segregates with markers between loci D3S1316 and D3S3710, which map to chromosome
      3q22.1-q24. Analysis using HOMOZ/MAPMAKER gave a maximum LOD score of 8.72. All
      five affected individuals were homozygous for the same allele, for two adjacent
      polymorphic markers within the region segregating with the disease, narrowing the
      region to 12 cM.

PMID- 10889049
TI  - Another look back.

PMID- 10889047
TI  - Identification of a novel gene on chromosome 7q31 that is interrupted by a
      translocation breakpoint in an autistic individual.
AB  - The results of genetic linkage studies for autism have suggested that a
      susceptibility locus for the disease is located on the long arm of chromosome 7
      (7q). An autistic individual carrying a translocation, t(7;13)(q31.3;q21), with
      the chromosome 7 breakpoint located in the region of 7q implicated by genetic
      studies was identified. A novel gene known as "RAY1" (or "FAM4A1") was found to
      be directly interrupted by the translocation breakpoint. The gene, which was
      found to be encoded by 16 exons with evidence of alternative splicing, spanned >
      or =220 kb of DNA at 7q31.3. Mutation screening of the entire coding region in a
      set of 27 unrelated autistic individuals failed to identify phenotype-specific
      variants, suggesting that coding region mutations are unlikely to be involved in
      the etiology of autism. Apparent homologues of RAY1 have also been identified in
      mouse, rat, pig, chicken, fruit fly, and nematode. The human and mouse genes
      share similar splicing patterns, and their predicted protein products are 98%
      identical.

PMID- 10889050
TI  - Age and origin of the PRNP E200K mutation causing familial Creutzfeldt-Jacob
      disease in Libyan Jews.

PMID- 10889051
TI  - The disequilibrium maximum-likelihood-binomial test does not replace the
      transmission/disequilibrium test.

PMID- 10889053
TI  - Pseudoautosomal linkage of Hodgkin disease.

PMID- 10889055
TI  - Evolution of nematode development.
AB  - Multiple evolutionary variations occur in the cellular and genetic programming of
      nematode development. Many changes involve alterations of inductive interactions.
      Surprisingly, inductive processes vary during evolution, irrespective of changes
      in the final cell lineages and morphological structures. Genetic studies in some
      nematodes also shed light on the underlying mechanisms of evolutionary change.

PMID- 10889056
TI  - Axial patterning in leaves and other lateral organs.
AB  - The establishment of abaxial-adaxial polarity in lateral organs involves factors
      intrinsic to the primordia and interactions with the apical meristem from which
      they are derived. Recent molecular genetic studies have identified some of the
      genes that promote either adaxial or abaxial cell fates, with many of the genes
      encoding spatially localized transcription factors.

PMID- 10889058
TI  - Drawing lines in the Drosophila wing: initiation of wing vein development.
AB  - It has been proposed that wing veins in Drosophila form at boundaries between
      discrete sectors of cells that subdivide the anterior-posterior axis of the
      developing wing primordium. Recently, analysis of events underlying initiation of
      vein formation suggests that there is a general developmental mechanism for
      drawing lines between adjacent domains of cells, which is referred to as 'for
      export-only-signaling'. In this model, cells in one domain produce a short range
      signal to which they cannot respond. As a consequence of this constraint, cells
      lying in a narrow line immediately outside the signal-producing domain are the
      only cells that can respond to the signal by activating expression of vein
      promoting genes.

PMID- 10889057
TI  - Body-plan evolution in the Bilateria: early antero-posterior patterning and the
      deuterostome-protostome dichotomy.
AB  - Recent molecular analyses reveal common themes in early antero-posterior
      patterning in the four major groups of invertebrate deuterostomes and vertebrates
      in spite of large differences in the mode of gastrulation. Comparisons with
      Drosophila and Cnidarians suggest a scheme for evolution of the Bilaterian body
      plan and emphasize the pressing need for similar studies in a wider variety of
      organisms, especially more basal protostomes.

PMID- 10889059
TI  - Control of developmental timing in Caenorhabditis elegans.
AB  - Studies of the nematode Caenorhabditis elegans have identified genetic and
      molecular mechanisms controlling temporal patterns of developmental events.
      Mutations in genes of the C. elegans heterochronic pathway cause altered temporal
      patterns of larval development, in which cells at certain larval stages execute
      cell division patterns or differentiation programs normally specific for other
      stages. The products of the heterochronic genes include transcriptional and
      translational regulators and two different cases of novel small translational
      regulatory RNAs. Other genes of the pathway encode evolutionarily conserved
      proteins, including a homolog of the Drosophila Period circadian timing
      regulator, and a member of the nuclear receptor family of proteins. These
      regulators interact with each other to elaborate stage-specific regulatory
      switches and act through downstream effectors to control the timing of cell-type
      specific developmental events.

PMID- 10889060
TI  - Constructive antagonism in limb development.
AB  - Several advances have been made in our understanding of the control of the growth
      and patterning of embryonic limbs. Development of the vertebrate limb is
      dependent on reciprocal interactions between the ectoderm and mesoderm that
      regulate the structure and function of the apical ectodermal ridge. One key
      component of this regulatory program appears to be the precise control of
      signaling by members of the bone morphogenetic protein family via multiple
      antagonistic interactions.

PMID- 10889061
TI  - Notch signal transduction: a real rip and more.
AB  - The Notch signaling pathway functions in a wide variety of processes that
      regulate tissue patterning and morphogenesis in developing vertebrates and
      invertebrates. Research on the mechanism of ligand-induced Notch signal
      transduction has revealed a novel and essential element in the signal cascade.
      Some recent findings support a model in which sequential proteolytic cleavage
      serves to regulate Notch signal transduction.

PMID- 10889062
TI  - Vertebrate mesendoderm induction and patterning.
AB  - Many of the key molecular events underlying the induction and patterning of the
      vertebrate mesoderm and endoderm have recently been elucidated. T-box
      transcription factors and TGF-beta and Wnt signaling pathways play crucial roles
      in the initial induction of the mesendoderm and the subdivision of the posterior
      mesoderm into rostral and caudal domains.

PMID- 10889063
TI  - Cytoplasmic flow and the establishment of polarity in C. elegans 1-cell embryos.
AB  - Early Caenorhabditis elegans embryos provide an excellent model for the study of
      developmental processes. Development can be studied by direct observation under
      the light microscope and can be perturbed using laser manipulations, drug
      inhibitor treatments, and genetic mutants. The first division of the C. elegans
      embryo is asymmetric, generating two daughter cells unequal in size and
      developmental fate. These distinct fates are generated by the partitioning of
      cytoplasmic determinants during the first mitotic cell cycle. Partitioning of
      these determinants is thought to be driven by cytoplasmic flow. Recent studies in
      C. elegans in the past year have identified a number of components necessary for
      this flow, giving us a clearer picture of the molecular mechanisms underlying
      developmental asymmetry.

PMID- 10889064
TI  - Retinoid signalling and hindbrain patterning.
AB  - Retinoid signalling has been implicated in regulating a wide variety of processes
      in vertebrate development. Recent advances from analyses on the synthesis,
      degradation and distribution of retinoids in combination with functional analysis
      of signalling components have provided important insights into the regulation of
      patterning the nervous system and the hindbrain in particular.

PMID- 10889065
TI  - Development of the root pole and cell patterning in Arabidopsis roots.
AB  - The root forms at the basal end of an axis that is set up early in embryogenesis,
      and recent genetic analysis has indicated that auxin transport is required for
      the formation of the root pole. Drug studies show that auxin transport is also
      required for the maintenance of the tissue organisation in the seedling root.
      These studies support existing models for tissue patterning that involve
      canalised auxin flow. Molecular insights into the mechanism of cell-type
      specification and patterning has come from the epidermis where positionally
      controlled cell specification is regulated by a cascade of transcription factors.

PMID- 10889066
TI  - Dictyostelium: a model for regulated cell movement during morphogenesis.
AB  - Dictyostelium has played an important role in unraveling the pathways that
      control cell movement and chemotaxis. Recent studies have started to elucidate
      the pathways that control cell sorting, morphogenesis, and the establishment of
      spatial patterning in this system. In doing so, they provide new insights into
      how cell movements within a multicellular organism are regulated and the
      importance of pathways that are similar to those that regulate chemotaxis of
      cells on two-dimensional surfaces during aggregation.

PMID- 10889067
TI  - Germ cells.
AB  - Recently, cell signaling has been shown to be required for the formation of germ
      cells in the mouse embryo, direct observation of germ cell migration in living
      mouse embryos has been achieved, novel genes that control germ-cell migration
      have been identified in Drosophila, and the roles of many components of germ
      plasm in several species have become clearer.

PMID- 10889068
TI  - Stepwise specification of lymphocyte developmental lineages.
AB  - B and T lymphocytes differentiate from multipotent precursors through distinct
      specification and commitment steps. New findings on the unique role of Pax5 in B
      lineage commitment, dichotomous action of Notch signaling in B versus T cell
      development, and the gene expression changes comprising T-lineage specification
      and commitment now illuminate this process.

PMID- 10889070
TI  - Author's reply

PMID- 10889069
TI  - Neural induction.
AB  - Development of neural fates from ectoderm is accompanied by the blockage of BMP
      signals at both protein and mRNA levels. Recent work has employed zebrafish,
      chick and mouse in addition to amphibians as models. Genetics has supplemented
      experimental embryology in enriching the understanding of the mechanism of neural
      induction and in posing new questions.

PMID- 10889071
TI  - Application of a new technique to a subtle diagnostic problem.

PMID- 10889072
TI  - Hot spots in age-related macular degeneration.

PMID- 10889073
TI  - High-altitude illness.

PMID- 10889074
TI  - Author's reply

PMID- 10889076
TI  - Author's reply

PMID- 10889075
TI  - Increased vertical fusional amplitudes.

PMID- 10889077
TI  - Increased vertical fusional amplitudes.

PMID- 10889078
TI  - Author's reply

PMID- 10889079
TI  - Pediatric photoscreening.

PMID- 10889080
TI  - Author's reply

PMID- 10889081
TI  - Determinants of optic disc characteristics.

PMID- 10889082
TI  - Author's reply

PMID- 10889084
TI  - Author's reply

PMID- 10889083
TI  - Screening of patients taking vigabatrin.

PMID- 10889085
TI  - Malignant glaucoma (aqueous misdirection) after pars plana vitrectomy.

PMID- 10889086
TI  - Our apologies

PMID- 10889087
TI  - Author's reply

PMID- 10889088
TI  - Cautions regarding measurements of the posterior corneal curvature.

PMID- 10889089
TI  - Topically applied nonsteroidal anti-inflammatory drugs and corneal problems: an
      interim review and comment.

PMID- 10889091
TI  - Discussion by edward J. Holland, MD

PMID- 10889090
TI  - Diffuse lamellar keratitis related to endotoxins released from sterilizer
      reservoir biofilms.
AB  - OBJECTIVE: To investigate the risk factors and control mechanisms used to control
      the outbreak of diffuse lamellar keratitis (DLK) associated with laser in situ
      keratomileusis (LASIK) and examine the relationship between DLK and endotoxins
      released from sterilizer biofilm reservoirs. DESIGN: Clinic-based cohort and
      laboratory study. PARTICIPANTS: All patients undergoing LASIK at our clinic from
      October 7, 1998 through August 31, 1999. The case definition was a diffuse
      infiltrate in the interface developing within the first week after surgery.
      INTERVENTIONS: Biofilm control in the sterilizer, changes in sterilizer,
      distilled water, instruments, and irrigating fluids. MAIN OUTCOME MEASURES: The
      incidence of DLK after LASIK surgery. RESULTS: There were 983 evaluable patients,
      with three whose DLK status was not recorded. There were 52 cases of DLK.
      Burkholderia pickettii was isolated from the sterilizer reservoir. Potential risk
      factors and associations, for which there was no significant difference, included
      age and sex of the patients, surgeon, operating suite temperature or humidity,
      drapes used, saline solutions used, time of day the surgery was performed, and
      microkeratome use. Sterilizers 1 and 2, before biofilm control, were compared
      with sterilizer 3, after control. The relative risk was 9.4 (confidence limits
      [CL], 7.5-11.8) for sterilizer 1 versus 3 and 18. 7 (CL, 11-32) for sterilizer 2
      versus 3. Three cases occurred after biofilm control, but were sporadic in nature
      and associated with epithelial defects. CONCLUSIONS: Clusters of DLK may be
      related to endotoxins released from gram-negative biofilms in sterilizer
      reservoirs. We experienced an outbreak of DLK affecting 52 patients and isolated
      B. pickettii from the sterilizer reservoir. Epidemiologic investigation showed
      that biofilm control in the sterilizer reservoirs was associated with a
      significant reduction in the development of DLK. We encourage any clinics that
      experience a cluster of DLK to consider microbiologic and epidemiologic
      investigation for the effectiveness of sterilizer biofilm control.

PMID- 10889092
TI  - Stromal wound healing explains refractive instability and haze development after
      photorefractive keratectomy: a 1-year confocal microscopic study.
AB  - PURPOSE: To evaluate the mechanism(s) producing refractive instability and
      corneal haze development after photorefractive keratectomy (PRK). DESIGN:
      Prospective, nonrandomized, comparative case series, self-controlled.
      PARTICIPANTS: Seventeen eyes of 17 patients with low- to moderate-grade myopia (
      2.88 to -9.13 diopters [D]) were included. METHODS: Surgical intervention was a
      standardized, 6-mm diameter PRK procedure using the Meditec MEL 60 excimer laser
      (Aesculap-Meditec, Heroldsberg, Germany). The photoablation center was evaluated
      before surgery and at 1, 3, 6, 9, and 12 months after PRK using rapid, continuous
      z-scans of confocal images, termed confocal microscopy through focusing (CMTF).
      MAIN OUTCOME MEASURES: Simultaneous epithelial and stromal thickness analysis and
      objective assessment of corneal light backscattering were obtained from digital
      image analysis of the CMTF scans. Corneal reinnervation and anterior stromal
      keratocyte density and wound healing morphologic features were evaluated on high
      resolution, in vivo confocal images. Manifest refraction was measured and corneal
      clarity was graded by slit-lamp biomicroscopy. RESULTS: Epithelial thickness
      averaged 45+/-10 microm at 1 month, 50+/-8 microm at 3 months, and 52+/-6 microm
      at 12 months after PRK, as compared with 51+/-4 microm before surgery,
      demonstrating complete restoration of the preoperative thickness without
      compensatory hyperplasia. Interestingly, epithelial rethickening had no
      significant correlation with refractive regression. By contrast, stromal regrowth
      (from 1-12 months) averaged 6+/-12 microm (range, 27 microm thinning-22 microm
      rethickening) and correlated closely (r = 0.84, P<0.001) with changes in
      refraction that averaged 0.84+/-1.23 D, ranging from -1.63 D (hyperopic shift) to
      +3.38 D (myopic regression). Stromal rethickening increased proportionally with
      the actual photoablation depth (r = 0.63, P<0.01); linear regression analysis
      suggested an average regrowth rate of 8% per year for the entire study group.
      Stromal rethickening was not associated with CMTF haze development over time,
      suggesting that haze and regression were caused by two independent wound healing
      mechanisms. In agreement with these findings, all "hazy" corneas showed increased
      numbers of anterior stromal wound healing keratocytes with increased reflectivity
      of both nuclei and cell bodies, suggesting that cellular-based reflections, as
      opposed to extracellular matrix deposition, are the major origin of increased
      corneal light scattering after PRK. CONCLUSIONS: Taken together, these data
      indicate that keratocyte-mediated regrowth of the photoablated stroma appears to
      be the main cause of myopic regression in humans treated with a 6-mm diameter
      PRK, whereas hyperopic shifts appear to be a direct consequence of stromal
      thinning. By contrast, the corneal epithelium appeared to restore its
      preoperative thickness without contributing significantly to the refractive
      changes after PRK. Finally, this study also provides strong evidence that the
      development of haze after PRK is directly associated with increased cellular
      reflectivity from high numbers of wound healing keratocytes.

PMID- 10889093
TI  - Shaken baby syndrome.
AB  - PURPOSE: To examine the comprehensive ophthalmologic experience with the shaken
      baby syndrome at one medical center, including clinical findings, autopsy
      findings, and the outcome of survivors. DESIGN: Retrospective, noncomparative
      case series. PARTICIPANTS: One hundred twenty-three children admitted from
      January 1987 through December 1998 for subdural hematomas of the brain secondary
      to abuse were included. METHODS: Clinical features of eye examinations of the
      patients during their admission and after discharge and histopathologic
      observations for patients who died were retrieved from medical records and
      statistically analyzed. MAIN OUTCOME MEASURES: Visual response and pupillary
      response on initial examination, fundus findings, final vision, neurologic
      outcome of survivors, and death. RESULTS: Ninety percent of the patients had
      ophthalmologic assessments. Retinal hemorrhages were detected in 83% of the
      examined children. The retinal hemorrhages were bilateral in 85% of affected
      children and varied in type and location. Nonophthalmologists missed the
      hemorrhages in 29% of affected patients. Poor visual response, poor pupillary
      response, and retinal hemorrhage correlated strongly with the demise of the
      child. One child who died had pigmented retinal scars from previous abuse, a
      condition not previously observed histopathologically to our knowledge. One fifth
      of the survivors had poor vision, largely the result of cerebral visual
      impairment. Severe neurologic impairment correlated highly with loss of vision.
      CONCLUSIONS: Shaken baby syndrome causes devastating injury to the brain and thus
      to vision. Retinal hemorrhages are extremely common, but vision loss is most
      often the result of brain injury. The patient's visual reaction and pupillary
      response on presentation showed a high correlation with survival. Good initial
      visual reaction was highly correlated with good final vision and neurologic
      outcome. According to the literature, when retinal hemorrhages are found in young
      children, the likelihood that abuse occurred is very high. Nonophthalmologists'
      difficulty in detecting retinal hemorrhages may be an important limiting factor
      in identifying shaken babies so they can be protected from further abuse.

PMID- 10889094
TI  - Cataract surgery in children with chronic uveitis.
AB  - OBJECTIVE: To evaluate the visual outcome of cataract surgery in children's eyes
      with chronic uveitis and the feasibility of intraocular lens (IOL) implantation
      in these cases. DESIGN: Retrospective noncomparative case series. PARTICIPANTS:
      Seventeen children (20 eyes) with chronic uveitis, dense cataract, and a
      preoperative visual acuity of 6/120 or less with follow-up of 5 years after the
      initial cataract surgery. METHODS: In 10 eyes of 10 children (five with juvenile
      rheumatoid arthritis [JRA] and five with non-JRA-associated uveitis) with
      uniocular or markedly unequal binocular disease, surgery was carried out through
      the limbus and a posterior chamber IOL was implanted. In seven children (10
      eyes), three with JRA and four with non-JRA-associated disease, a pars plana
      approach was used, and contact lenses or glasses (for the bilateral cases) were
      prescribed. RESULTS: The postoperative course and immediate restored visual
      acuities were similar whether an IOL was implanted or not. One month after the
      surgery, visual acuity improved in all operated eyes. After monocular surgery, in
      the younger children, contact lenses were poorly tolerated and their use
      discontinued. These aphakic eyes remained with low vision, developing strabismus
      on longer follow-up. Children with JRA-associated uveitis were younger,
      demonstrated an active intraocular inflammation for an extended period after
      surgery, and tended to have secondary membranes develop, necessitating a second
      surgical intervention. Five years after the initial surgery, only two of nine
      eyes (22%) in the JRA group (one aphakic of a bilaterally affected child and one
      pseudophakic in a child undergoing cataract surgery in one eye) retained a visual
      acuity of 6/9 and 6/6, respectively. In the other seven eyes, the visual acuity
      was 6/60 in one pseudophakic eye and 6/240 or less in six eyes (three aphakic and
      three pseudophakic). In children with non-JRA-associated uveitis, 6 (four aphakic
      in two patients bilaterally affected and two pseudophakic) of 11 eyes (54.5%)
      retained a vision of 6/12 or better. CONCLUSIONS: Cataract surgery in children's
      eyes with uveitis may be beneficial. IOL implantation seems preferable to
      correction with contact lenses in young children needing surgery in one eye. In
      children with JRA-associated uveitis, the final visual results remain guarded
      because of irreversible amblyopia and a more complicated postoperative course.
      For these cases, a modified management approach and a better surgical technique
      are needed.

PMID- 10889095
TI  - Bilateral intraocular lens implantation in the pediatric population.
AB  - PURPOSE: To evaluate bilateral intraocular lens (IOL) implantation in children.
      DESIGN: Retrospective, noncomparative case series PARTICIPANTS: Thirty pediatric
      patients with bilateral IOL implants at one institution with more than 6 months
      of followup. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES:
      Complications, visual acuity, axial length, and refractive changes were recorded.
      RESULTS: Thirty patients (60 eyes) had an average followup of 31 months (range, 7
      69 months). Average age at implantation was 73 months (range, 12 days-13 years).
      At last followup, 91% of eyes had vision better than or equal to 20/40. Patients
      in the youngest age group (<2 years) demonstrated the most rapid refractive and
      axial length changes, and there were progressively smaller changes in older age
      groups. Only four patients had acuity differences between eyes of more than one
      line. CONCLUSIONS: Bilateral IOLs are safe and effective in pediatric aphakia.

PMID- 10889096
TI  - Incidence and progression of lens opacities in the Barbados Eye Studies.
AB  - OBJECTIVE: To provide 4-year cumulative incidence and progression rates of age
      related lens opacities in a population > or =40 years of age, which is mainly of
      African origin. DESIGN: Cohort study that reexamined surviving members of the
      population-based Barbados Eye Study 4 years after baseline. PARTICIPANTS: Three
      thousand four hundred twenty-seven members of the Barbados Eye Study cohort (85%
      of those eligible). MAIN OUTCOME MEASURES: The Lens Opacities Classification
      System II (LOCS II) was used at the slit lamp. Cumulative incidence was defined
      as the development of any nuclear, cortical or posterior subcapsular (PSC)
      opacities (LOCS II scores > or =2) among persons without that opacity type at
      baseline. Cumulative progression was defined by at least two-step increases in
      scores among persons with preexisting lens opacities. RESULTS: The incidence of
      cortical opacities was about five times greater in black than white participants
      (age-gender adjusted relative risk = 4.7; 95% confidence interval: 1.9-11.4). In
      the black population, the 4-year incidence rates were 22.2% (20.4%-24.0%) for any
      cortical, 9.2% (8.2%-10.4%) for any nuclear, and 3.3% (2.7%-4.0%) for any PSC
      opacities; rates increased greatly with age. Four-year progression rates were
      12.5% for cortical, 3.6% for nuclear, and 23.0% for PSC opacities, without
      consistent pattern by age. Women had a greater risk of cortical and nuclear
      opacities (P<0.05) than men and greater progression of nuclear opacities. The
      presence of PSC opacities at baseline seemed to at least double the incidence and
      progression rates of other opacities. In persons initially opacity free, single
      cortical opacities were the predominant type to develop at followup. Visual
      acuity loss frequently accompanied incident opacities. CONCLUSIONS: This
      longitudinal study provides new population-based data on the natural history of
      lens opacities. Incidence and progression of opacities, especially of cortical
      opacities, were high. After 4 years of followup, 1 in 4 to 5 participants
      developed cortical opacities, 1 in 11 developed nuclear opacities, and 1 in 30
      developed PSC opacities. The information obtained attests to the public health
      impact of age-related cataract, as well as its extent, in this and similar black
      populations.

PMID- 10889098
TI  - Postoperative Mycobacterium chelonae endophthalmitis after extracapsular cataract
      extraction and posterior chamber intraocular lens implantation.
AB  - OBJECTIVE: To describe a case of postoperative endophthalmitis caused by
      Mycobacterium chelonae after extracapsular cataract extraction with posterior
      chamber intraocular lens implantation. DESIGN: Interventional case report.
      METHODS: The history and clinical presentation of a 66-year-old female patient,
      in whom a low-grade delayed-onset endophthalmitis and keratitis developed after
      extracapsular cataract extraction with posterior chamber intraocular lens
      implantation, is described. Microbiologic investigations of the scrapings of
      corneal infiltrate at the cataract incision site, aqueous humor and eviscerated
      material, and histopathologic study of eviscerated material and an enlarged
      cervical lymph node were performed. MAIN OUTCOME MEASURES: The clinical,
      histopathologic, and microbiologic findings in a case of low-grade delayed-onset
      endophthalmitis. RESULTS: Analysis of the direct smear of both the corneal
      infiltrate as well as the eviscerated material revealed acid-fast bacilli. M.
      chelonae was isolated from these specimens. Direct smear and culture of the
      aqueous humor were negative for bacteria (including mycobacteria) and fungus.
      Histopathologic examination of the eviscerated material showed a dense
      infiltration of polymorphonuclear leukocytes in the uveal tissue, extensive
      necrosis and hemorrhage, and exudates with hemorrhage in the vitreous cavity.
      Histopathologic examination of the lymph node revealed granulomatous inflammation
      with caseation necrosis, but did not reveal acid-fast bacilli. CONCLUSIONS: M.
      chelonae, although infrequent, should be considered an etiologic agent of delayed
      onset, postoperative endophthalmitis and early bacterial diagnosis should help in
      institution of appropriate therapy.

PMID- 10889097
TI  - Characteristics after cataract extraction or secondary lens implantation among
      patients screened for the Endophthalmitis Vitrectomy Study.
AB  - PURPOSE: This report describes the presenting clinical ophthalmic features and
      historical findings in patients with a clinical diagnosis of endophthalmitis
      after cataract extraction or secondary lens implant surgery screened for
      enrollment in the Endophthalmitis Vitrectomy Study (EVS). DESIGN: Clinic-based,
      cross-sectional study. PARTICIPANTS: Eight hundred fifty-four patients suspected
      to have endophthalmitis after cataract extraction or secondary lens implantation.
      METHODS: As part of the screening process for the study, an eye examination, a
      medical history, and demographic data were recorded in standardized form for all
      patients with endophthalmitis after cataract extraction or secondary lens implant
      surgery referred to the clinical centers, regardless of whether the patient met
      entry criteria. MAIN OUTCOME MEASURES: Demographics, presenting signs, and
      symptoms. RESULTS: The median age of individuals presenting with suspected
      bacterial endophthalmitis was 75 years (range, 9-100 years). Most of those
      screened (57.7%) were women. Seventy-nine percent of patients sought treatment
      within 6 weeks of surgery. Blurred vision, conjunctival injection, pain, and lid
      swelling were the predominant presenting symptoms in order of prevalence. Ocular
      pain and hypopyon, widely regarded as diagnostic of endophthalmitis, were each
      absent in 25% of patients. The median hypopyon height, when present, was 1.5 mm.
      CONCLUSIONS: The classic presentation of postoperative endophthalmitis includes
      reduced vision, conjunctival hyperemia, pain, hypopyon, and lid swelling within
      days after cataract surgery or secondary lens implantation. These were the
      prominent clinical findings in the EVS as well. Because pain and hypopyon,
      although common, were not always present, clinicians must be vigilant in
      postsurgical monitoring of patients.

PMID- 10889099
TI  - Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study.
AB  - OBJECTIVE: To assess the impact of vascular risk factors on the prevalence of
      primary open angle glaucoma. DESIGN: Population-based cross-sectional study.
      PARTICIPANTS: Four thousand two hundred ninety-seven patients more than 40 years
      of age underwent a complete ocular examination in the context of the Egna
      Neumarkt Glaucoma Study. INTERVENTION: Ocular examinations were performed by
      trained, quality-controlled ophthalmologists according to a predefined
      standardized protocol including medical interview, blood pressure reading,
      applanation tonometry, computerized perimetry, and optic nerve head examination.
      MAIN OUTCOME MEASURES: Prevalences of ocular hypertension, primary open-angle
      glaucoma, normal-tension glaucoma, and other types of glaucoma were determined.
      Correlation coefficients were calculated for the association between systemic
      blood pressure and age-adjusted intraocular pressure (IOP) and between age and
      both intraocular and systemic blood pressures. Odds ratios were computed to
      assess the risk of primary open-angle glaucoma and normal-tension glaucoma in
      relation to systemic hypertension or antihypertensive medication, blood pressure
      levels, diastolic perfusion pressure, and a number of other cardiovascular risk
      factors. RESULTS: A positive correlation was found between systemic blood
      pressure and IOP, and an association was found between diagnosis of primary open
      angle glaucoma and systemic hypertension. Lower diastolic perfusion pressure is
      associated with a marked, progressive increase in the frequency of hypertensive
      glaucoma. No relationship was found between systemic diseases of vascular origin
      and glaucoma. CONCLUSIONS: Our data are in line with those reported in other
      recent epidemiologic studies and show that reduced diastolic perfusion pressure
      is an important risk factor for primary open-angle glaucoma.

PMID- 10889100
TI  - Screening relatives of patients with familial chronic open angle glaucoma.
AB  - PURPOSE: To describe the value and the results of screening of family members of
      individuals with familial chronic open-angle glaucoma (COAG) for the disease.
      DESIGN: Cross-sectional study of families with COAG. PARTICIPANTS: Eighty-six
      individuals from 15 families with COAG. TESTING: Complete ophthalmologic
      examinations, automated perimetry, and optic nerve photography. MAIN OUTCOME
      MEASURES: Disease status as glaucoma patient (at least two of three parameters
      abnormal: intraocular pressure, visual field, or disc appearance), glaucoma
      suspect (one of three parameters abnormal), or normal. RESULTS: Twenty-six
      relatives were diagnosed with COAG. The diagnosis was most frequently made on the
      basis of intraocular pressure readings and automated perimetry. Twenty-three
      relatives were classified as glaucoma suspects; automated perimetry was the most
      useful modality for the detection of abnormalities in these individuals. Siblings
      of COAG patients had the highest risk of COAG developing (64.7%) compared with
      children (13.2%) or other blood relatives (22.2%). CONCLUSIONS: When COAG is
      present in more than one family member, immediate and other relatives should be
      evaluated for glaucoma by means of clinical examination and automated perimetry.

PMID- 10889101
TI  - Trabeculectomy for acute primary angle closure.
AB  - OBJECTIVE: To analyze the results of trabeculectomy performed for all cases of
      acute primary angle closure (APAC). DESIGN: Retrospective, noncomparative case
      series PARTICIPANTS: Fifty-six consecutive patients who underwent trabeculectomy
      for APAC at two Singapore centers from 1993 through 1995. METHODS: The
      conventional treatment for APAC is to lower intraocular pressure (IOP) medically,
      after which laser peripheral iridotomy (PI) is performed. However, in Asian eyes,
      the acute attack is often refractory to standard treatment. Trabeculectomy is
      occasionally performed on eyes that do not respond to medical therapy, as well as
      eyes with APAC that respond to medical therapy but are assessed as having
      underlying chronic angle-closure glaucoma. In such cases, laser PI is not
      performed before trabeculectomy. MAIN OUTCOME MEASURES: The surgical outcome was
      assessed in terms of final IOP and the incidence of complications. Success was
      defined as final IOP less than 21 mmHg without medication, and qualified success
      was defined as final IOP less than 21 mmHg with medication. Patients whose IOP
      was more than 21 mmHg, required further glaucoma surgery, lost light perception,
      or whose eye became phthisical were classified as failures. RESULTS: The mean
      follow up was 22 months (range, 6-42 months). In group A, the medical failure
      group (n = 32), success in IOP control was obtained in 18 patients (56.2%),
      qualified success was achieved in 3 patients (9.4%), and failure resulted in 11
      patients (34.4%). Ten patients (31.3%) encountered early postoperative
      complications such as shallow anterior chamber. In group B, the medical success
      group (n = 24), success in IOP control was achieved in 21 patients (87.5%),
      qualified success was achieved in 3 patients (12.5%), and there were no cases of
      failure. The incidence of postoperative complications was low (4 eyes [16.7%]).
      In terms of IOP outcome, trabeculectomy outcome was significantly worse in group
      A (P<0.001, Fisher's exact test). CONCLUSIONS: Because there is a high risk of
      surgical failure and complications, trabeculectomy may not be the procedure of
      choice in medically unresponsive cases of APAC.

PMID- 10889102
TI  - Sensitivity of Swedish interactive threshold algorithm compared with standard
      full threshold algorithm in Humphrey visual field testing.
AB  - OBJECTIVE: To compare the sensitivity of Swedish interactive threshold algorithm
      (SITA) strategies with the standard full threshold algorithm in the Humphrey
      Field Analyzer. DESIGN: Observational case series. PARTICIPANTS: Forty-eight
      glaucoma patients who were experienced in automated perimetry. TESTING: Central
      field testing was performed with the 30-2 program using standard full threshold
      (SFT), SITA standard (SS), and SITA fast (SF) strategies. All three tests were
      carried out on each of four different days in a span of 4 weeks. MAIN OUTCOME
      MEASURES: Sensitivity, repeatability, time saved, and the extent of defect in the
      SITA strategies were compared with those of the SFT. RESULTS: The sensitivity of
      SS and SF were 95.12% and 92.68%, respectively. The time saved in SS and SF was
      53.12+/-9.51% and 70.69+/-8.81%, respectively. The repeatability as assessed by
      intraclass correlation showed excellent repeatability for the SFT and SS
      strategies and excellent to poor repeatability with the SF strategy. With
      increasing mean deviation, the defects (significant at P<0.5%) in the pattern
      deviation plots tended to be more in the SITA strategies as compared with SFT.
      CONCLUSIONS: Swedish interactive threshold algorithm strategies have good
      sensitivity and are significantly faster as compared with the standard threshold
      algorithm. The repeatability of the SFT and SS strategies are excellent, whereas
      that of the SF strategy is variable.

PMID- 10889103
TI  - Discussion by gordon R. Douglas, MD

PMID- 10889104
TI  - A comparison of optical coherence tomography and retinal nerve fiber layer
      photography for detection of nerve fiber layer damage in glaucoma.
AB  - PURPOSE: To compare optical coherence tomography (OCT) retinal nerve fiber layer
      (RNFL) thickness measurements with established methods for assessment of
      glaucomatous damage using RNFL photography and visual field testing. DESIGN:
      Cross-sectional study. PARTICIPANTS: Fifty-eight eyes of 58 healthy volunteer
      ocular hypertensive patients, glaucoma suspect patients, and glaucoma patients
      were included. METHODS: Optical coherence tomography 3.4-mm diameter circular
      scans were obtained within 3 months of RNFL photography and standard achromatic
      visual field testing. Three independent observers graded RNFL photographs using
      two standardized protocols. For each method, superior and inferior arcuate
      bundles were scored separately, and interobserver and intraobserver variation was
      measured. Standard achromatic visual field mean deviation in the superior and
      inferior hemifields was compared with RNFL damage as assessed by photography and
      OCT RNFL thickness measurements. MAIN OUTCOME MEASURES: Visual field mean
      deviation and severity of glaucomatous RNFL damage as assessed by photography.
      RESULTS: Optical coherence tomography RNFL thickness decreased with increasing
      RNFL damage as assessed by photography using both methods of photographic
      assessment. Standard achromatic perimetry mean deviation was significantly
      associated with OCT RNFL thickness (R(2) = 35%-43%) and RNFL photography severity
      score (R(2) = 18%-29%). CONCLUSIONS: These results suggest that the OCT shows
      promise for providing quantitative measures of RNFL thickness for diagnosing and
      monitoring glaucoma.

PMID- 10889105
TI  - Computerized stereochronoscopy and alternation flicker to detect optic nerve head
      contour change.
AB  - PURPOSE/BACKGROUND: Stereochronoscopy, a technique previously explored but
      abandoned for glaucoma diagnosis, viewed optic nerve images acquired at separate
      points in time as if a stereo pair. Prior efforts to exploit this technique were
      impaired by a lack of superimposability for sequential optic nerve images. We
      investigated computerized registration techniques for aligning sequential,
      monoscopic optic disc images to facilitate sensitive detection of optic nerve
      head contour changes in glaucoma. DESIGN: Algorithm and software development.
      Comparisons with standard techniques. MATERIALS: Existing patient records from
      the Glaucoma Service, Scheie Eye Institute, University of Pennsylvania. METHODS:
      Two sets of optic disc photographs, separated in time by 1 to 18 years, of 25
      eyes with and without glaucomatous optic disc progression were digitized. We
      developed custom software for accurate image alignment. Change in disc morphology
      was then judged by digital stereochronoscopy and user-controlled alternation
      flicker of superimposed, time-separated images on a computer monitor. Comparisons
      were made with standard stereoscopic comparison. MAIN OUTCOME MEASURE:
      Identification of change or no change in optic nerve head contour for images
      acquired at separate points in time. RESULTS: Image processing and registration
      permits accurate alignment of optic disc photographs. Alternation flicker of
      superimposed, sequential images facilitates image comparison and detection of
      change as indicated by change in vessel position, color, and other cues for
      contour change. A high concordance was found between standard stereoscopic
      comparison and alternation flicker. In several cases, reinspection of stereo
      comparison led to a revised judgment on the basis of disc changes rendered more
      obvious with alternation flicker. Digital stereochronoscopy was less concordant
      with standard techniques. CONCLUSIONS: Digital image processing techniques and
      alternation flicker provide a simple, sensitive, software-based method for
      detecting glaucomatous optic disc change.

PMID- 10889106
TI  - Thickness of the peripapillary retina in healthy subjects with different degrees
      of ametropia.
AB  - PURPOSE: To evaluate the thickness of the peripapillary retina in healthy
      subjects with different degrees of ametropia. DESIGN: Cross-sectional study.
      PARTICIPANTS: Forty-three healthy normal subjects, ages 15 to 64 years (38+/-15
      years) were recruited. METHODS: The method of retinal thickness mapping was
      applied to generate serial optical section images in the temporal peripapillary
      retinal area. The digitized images were analyzed to detect the separation between
      the vitreoretinal and chorioretinal interfaces. The separation was converted to
      absolute thickness by taking into account the magnification of the optical system
      and the optical dimensions of the eyes. MAIN OUTCOME MEASURES: The refractive
      error of the eyes ranged from +8.25 to -12.75 diopters (spherical equivalent).
      The axial length of the eyes ranged from 19.3 to 27.35 mm. The retinal thickness
      in a 2- x 2-mm temporal peripapillary retinal area was determined. RESULTS: The
      separation between the retinal interfaces decreased with increasing axial length
      (P<0.001). The thickness in the temporal peripapillary retinal area was not
      significantly correlated with the axial length of the eye (P = 0.3). A lack of
      statistically significant difference between the average thickness in the
      hyperopic, emmetropic, and myopic eyes (P> or =0.06) was found. CONCLUSIONS: The
      average thickness in the temporal peripapillary retinal area was not influenced
      by the axial length of the eye, when the magnification of the optical system and
      the optical dimension of the eyes were taken into consideration.

PMID- 10889107
TI  - Changes in anterior and posterior corneal curvatures in keratoconus.
AB  - OBJECTIVE: To quantitatively evaluate the changes in anterior and posterior
      corneal curvatures of eyes with keratoconus. DESIGN: Case-control retrospective
      and observational study. PARTICIPANTS: Thirty-one patients who were clinically
      diagnosed to have unilateral or bilateral keratoconus and 18 normal subjects.
      INTERVENTION: The anterior and posterior topographies were obtained using
      scanning-slit videokeratography and assessed by Fourier series harmonic analysis.
      MAIN OUTCOME MEASURES: Quantitative descriptors of the topography data, spherical
      power, regular astigmatism, and irregular astigmatism (asymmetry and higher order
      irregularity) components were compared between the anterior and posterior
      surfaces and among groups of clinically diagnosed keratoconus (33 eyes),
      keratoconus suspect (13 eyes), and normal subjects (36 eyes). RESULTS: Spherical
      power (P = 0.0003, Mann-Whitney U test with Bonferroni's correction of P values),
      regular astigmatism (P = 0.0166), and asymmetry (P = 0.0031) of the anterior
      surface were significantly greater in the keratoconus eyes than in the normal
      controls. For the posterior surface, spherical power (P<0.0001), regular
      astigmatism (P = 0.0143), asymmetry (P< 0.0001), and higher order irregularity (P
      = 0.0032) of the keratoconus group were significantly greater than those of the
      control group. The keratoconus suspect eyes, when compared with the normal
      controls, showed a significantly greater amount of spherical power (P = 0. 0166)
      and asymmetry (P<0.0001) in the anterior surface and spherical power (P <0.0001),
      regular astigmatism (P = 0.0244), asymmetry (P<0.0001), and higher order
      irregularity (P = 0.0276) in the posterior surface. All refractive components
      demonstrated statistically significant correlations between the anterior and
      posterior surfaces (P<0.0001, Spearman's rank correlation). CONCLUSIONS: Not only
      the anterior but also the posterior corneal curvature is affected in keratoconus.
      These changes are observed from the early stage of this disorder.

PMID- 10889108
TI  - A standardized visual scale for evaluation of tear fluorescein clearance.
AB  - OBJECTIVE: To evaluate the correlation and the agreement between a validated
      fluorometric technique (fluorescein clearance test) and a newly developed,
      clinically practical standardized visual scale to evaluate tear fluorescein
      clearance. Also, the ability of this new method to distinguish healthy persons
      from patients reporting ocular irritation associated with meibomian gland disease
      (MGD), aqueous tear deficiency (ATD), or both was tested. DESIGN: Case-controlled
      study. PARTICIPANTS: Healthy persons (n = 32), patients with MGD associated with
      rosacea (n = 30), patients with noninflammatory atrophic MGD (n = 24), and
      patients with ATD (n = 39) were evaluated. There was a similar age and gender
      distribution in each group. METHODS: Each subject completed a symptom
      questionnaire and had the following tests performed: fluorescein clearance test
      (FCT), standardized visual scale test (SVST), corneal fluorescein staining,
      Schirmer 1 test, corneal and conjunctiva sensitivity, and eyelid margin and
      meibomian gland examination. MAIN OUTCOME MEASURES: The FCT was performed with a
      CytoFluor II fluorophotometer by measuring the fluorescein concentration in
      minimally stimulated tear samples collected from the inferior tear meniscus 15
      minutes after instillation of 5 microl of 2% sodium fluorescein. The SVST score,
      ranging from 0 to 6, was obtained by comparing the colors of the standardized
      visual scale with the color of the lateral inferior tear meniscus immediately
      before tear collection for the FCT. Severity of ocular irritation was assessed
      with a symptom questionnaire. Schirmer 1 test (without anesthesia),
      biomicroscopic meibomian gland evaluation, and corneal fluorescein staining were
      performed. Corneal and conjunctival sensitivity scores were assessed with the
      Cochet-Bonnet aesthesiometer. The correlation and the agreement between FCT, FCT
      corrected for Schirmer test (corrected FCT), SVST, and SVST corrected for
      Schirmer test (corrected SVST) in separating healthy persons from patients with
      ATD, MGD, or both were studied. Furthermore, the correlations of FCT, corrected
      FCT, SVST and corrected SVST, corneal fluorescein staining score, corneal and
      conjunctiva sensitivity, meibomian gland and eyelid evaluation, and questionnaire
      score were studied. RESULTS: The FCT, the corrected FCT, the SVST, and the
      corrected SVST all showed strong correlation with irritation symptoms, corneal
      fluorescein staining, Schirmer 1 test score, cornea and conjunctiva sensitivity,
      and meibomian gland and eyelid pathologic characteristics. The FCT, the corrected
      FCT, the SVST, and the corrected SVST had a sensitivity in diagnosing MGD,
      respectively, of 67%, 72%, 69%, and 76%, and of 95%, 97%, 97%, and 97% in
      diagnosing ATD. The specificity was, respectively, 97%, 96%, 97%, and 94%.
      CONCLUSIONS: The new standardized visual scale test was equivalent to
      fluorometric assessment of tear clearance in its correlation with irritation
      symptoms, ocular surface and eyelid disease, and ocular surface sensitivity. Its
      ability to separate healthy persons from patients with MGD and ATD was improved
      by applying a correction factor based on Schirmer test score. The new
      standardized visual scale test is an accurate and practical method for clinical
      assessment of fluorescein tear clearance.

PMID- 10889109
TI  - Hypopyon after repeated transplantation of human amniotic membrane onto the
      corneal surface.
AB  - OBJECTIVE: The authors describe a localized probable immunoreaction after
      repeated transplantation of amniotic membrane (AM) onto the corneal surface.
      DESIGN: Interventional case report. INTERVENTION: Amniotic membrane was
      transplanted onto the corneal surface of a 78-year-old female with a deep trophic
      corneal ulcer resulting in temporary epithelial closure. A second and finally
      third amniotic membrane transplantation (AMT) was performed because of recurrent
      ulcerations. All three AMs were obtained from the same donor. RESULTS: The first
      transplantation of the AM was without complication. However, a hypopyon developed
      2 days after the second and 2 days after the third AMT, but the patient responded
      immediately to topical and systemic corticosteroids. CONCLUSIONS: Immunologic,
      toxic, and hypersensitivity effects could have contributed to the hypopyon iritis
      that appeared after the second and third AMT, but not after the initial
      transplantation. In case of a repeated AMT, the use of AM from different donors
      may help to minimize the risk of an immediate postoperative intraocular
      inflammation.

PMID- 10889111
TI  - Discussion by jules L. Baum, MD

PMID- 10889110
TI  - Topical treatment with nerve growth factor for neurotrophic keratitis.
AB  - OBJECTIVE: To evaluate the efficacy of nerve growth factor (NGF) in patients with
      neurotrophic keratitis. DESIGN: Prospective, noncomparative, interventional case
      series. PARTICIPANTS: Forty-five eyes of 43 consecutive patients with moderate
      (stage 2, n = 17) to severe (stage 3, n = 28) neurotrophic keratitis unresponsive
      to other nonsurgical therapies. METHODS: After a 10-day washout with preservative
      free artificial tears, 45 eyes with neurotrophic keratitis received murine NGF
      (200 microg/ml) every 2 hours for 2 days followed by one drop six times daily
      until the ulcer healed. A maintenance dose of one drop NGF (100 microg/ml) was
      administered four times daily for the 2 weeks subsequent to ulcer healing. MAIN
      OUTCOME MEASURES: Size and depth of the ulcer or the epithelial defect, corneal
      sensitivity, best corrected visual acuity, side effects, and relapse of the
      disease in the follow-up period. RESULTS: All patients had a complete resolution
      of the persistent epithelial defect (with or without an ulcer) after 12 days to 6
      weeks of treatment with NGF. Patients affected by both stages of the disease
      demonstrated both improved corneal sensitivity and visual acuity (P<0.001). No
      significant differences were observed in the time to complete corneal healing
      between stage 2 and stage 3 patients. Hyperemia and ocular and periocular pain
      were side effects reported during the first days of treatment. No relapse of the
      disease was observed during the follow-up period, with the exception of three
      patients with trigeminal nerve resection, who required a single retreatment.
      CONCLUSIONS: Nerve growth factor eye drops improved corneal sensitivity and
      promoted corneal epithelial healing in both moderate and severe neurotrophic
      keratitis. Although performed in an uncontrolled and nonrandomized series of
      patients, this therapy shows promise for the restoration of ocular surface
      integrity and visual function in neurotrophic corneal disease.

PMID- 10889112
TI  - Clinical, histologic, and ultrastructural features of the corneal dystrophy
      caused by the R124L mutation of the BIGH3 gene.
AB  - OBJECTIVE: This study was designed to describe the clinical, histologic, and
      ultrastructural features of the corneal dystrophy associated with the R124L
      mutation of the BIGH3 gene. DESIGN: Retrospective clinical and histologic review
      of a new genetic mutation. PARTICIPANTS: Thirty-four patients from five unrelated
      French families with corneal dystrophy caused by the R124L mutation of the BIGH3
      gene were studied at the clinical, histologic, and ultrastructural levels.
      Records of patients carrying this mutation were compared with those from three
      unrelated patients with corneal dystrophy of Bowman's layer (CDB) type 2 (R555Q
      mutation) and from three unrelated patients with classic corneal granular
      dystrophy (R555W mutation). INTERVENTION: The mutational genetic status of the
      BIGH3 gene was determined for each patient, and the histologic and
      ultrastructural data available after corneal graft were analyzed. MAIN OUTCOMES
      MEASURES: Genomic DNA was extracted from peripheral blood leukocytes. Exons 4 and
      12 of the BIGH3 gene were amplified by the polymerase chain reaction (PCR), and
      the PCR products were directly sequenced. RESULTS: All 34 patients with the R124L
      mutation displayed the clinical, histologic, and electron microscopic features of
      the dystrophy previously described as a superficial variant of corneal granular
      dystrophy. Combining molecular genetics with clinical and histologic findings
      established a clear distinction between the R555Q and R555W dystrophies.
      CONCLUSIONS: The R124L mutation of the BIGH3 gene is associated with specific
      clinical and morphologic criteria. This indicates that molecular studies are
      needed for an adequate classification of corneal dystrophies. All criteria are
      presently available to segregate the dystrophy caused by the R124L mutation
      (known as CDB1) from the dystrophy caused by the R555Q mutation (known as CDB2).

PMID- 10889113
TI  - Morphologic characteristics of disciform scarring after radiation treatment for
      age-related macular degeneration.
AB  - OBJECTIVE: To investigate the influence of radiation therapy on the development
      of disciform lesions in patients with age-related macular degeneration (AMD).
      DESIGN: A prospective, nonrandomized, comparative trial (patient self
      controlled). PARTICIPANTS: Forty eyes with exudative AMD involving the central
      fovea in 40 consecutive patients were enrolled in this study. INTERVENTION:
      Radiation was administered to the posterior pole with an 8-mV photon beam from a
      linear accelerator. A dose of 14.4 Gy, 1.8 Gy per day, five fractions per week
      was delivered through a single port. MAIN OUTCOME MEASURES: The visual acuity and
      the morphologic characteristics, demonstrated by fundus photography, fluorescein,
      and indocyanine green angiography, were investigated before treatment and every 3
      months after treatment over a period of 24 months. In 10 patients with bilateral
      disease the disciform lesions were compared. RESULTS: Twenty five patients could
      be followed regularly over the period of 24 months. The disciform lesions
      occurring after radiation were classified in three types. Type I (10 patients)
      was characterized by being smaller than 2 DD in size, with little fibrotic tissue
      underneath the retina, but pronounced retinal pigment epithelial changes. Type II
      (seven patients) showed extensive growth of the choroidal neovascularization
      (CNV) extending to and beyond the arcades with angiographically active loops in
      the peripheral parts. Eight patients had type III lesions develop characterized
      by a size greater than 2 DD but fewer than 6 DD and by a different amount of
      fibrotic tissue, hemorrhage, and lipid. Type I scarring was significantly
      associated with occult CNV without pigment epithelial detachments, whereas type
      II scarring was associated with classic CNV at the initial presentation (P<0.05).
      CONCLUSIONS: Although no severe side effects have been reported after radiation
      therapy for AMD, a subgroup of patients may experience extensive growth of CNV
      after radiation, causing greater functional damage than occurs spontaneously.

PMID- 10889114
TI  - The possibility of gene therapy for the treatment of choroidal
      neovascularization.
AB  - PURPOSE: Choroidal neovascularization (CNV) is responsible for most cases of
      severe visual loss in age-related macular degeneration. Recently, the possibility
      of gene therapy has been proposed for the treatment of CNV. The purpose of this
      study was to examine the feasibility of ex vivo and in situ gene therapy
      approaches for CNV. DESIGN: Experimental study. METHODS: Human retinal pigment
      epithelial (RPE) cells were transduced with a retroviral vector coding for beta
      galactosidase. Transduced cells were grown on type II collagen sheets and
      transplanted under the retina of 20 rabbits. Animals were observed for 3 to 56
      days, and transplanted cells were examined histologically and with X-gal
      staining. Bovine choroidal endothelial cells (CEC) were transduced with
      retroviral vectors coding for tissue inhibitor of metalloproteinase-2 (TIMP-2) or
      control vector. Production of TIMP-2 by transduced cells was determined by
      immunohistochemical analysis and enzyme-linked immunosorbent assay. Effect of
      transduction on in vitro proliferation, migration, and tube formation was
      examined in response to vascular endothelial growth factor (VEGF). Four CNV
      lesions were induced in one cynomolgus monkey by laser photocoagulation. Two days
      later, retroviral vector coding for TIMP-2 or control vector was injected into
      the subretinal space overlying the CNV lesions. The monkey was observed for 12
      weeks using fluorescein angiography. RESULTS: Transplantation of transduced RPE
      cells was technically achieved in 10 of 20 animals. In these animals, RPE cells
      at the site of transplantation formed a monolayer and expressed beta
      galactosidase for 14 days. beta-Galactosidase-positive cells were not identified
      at 56 days. Choroidal endothelial cells transduced with TIMP-2 secrete TIMP-2
      into the media and show decreased migration and tube formation in vitro. In the
      in vivo monkey model, the control CNV lesions (n = 2) showed prominent leakage,
      whereas the experimental lesions (n = 2) showed minimal hyperfluorescence.
      CONCLUSIONS: Retrovirally transduced RPE cells survive in the subretinal space
      for at least 14 days and continue to express the gene product coded for by the
      vector. Choroidal endothelial cells retrovirally transduced for TIMP-2 produce
      TIMP-2 in vitro and show decreased angiogenic responses in vitro in response to
      VEGF. A preliminary study attempting in situ delivery of TIMP-2 vector to CNV
      lesions in a monkey eye supports the feasibility of this approach and encourages
      further study.

PMID- 10889115
TI  - Incremental cost effectiveness of laser photocoagulation for subfoveal choroidal
      neovascularization.
AB  - OBJECTIVE: To perform a patient preference-based, incremental cost-effectiveness
      analysis for laser treatment of subfoveal choroidal neovascularization. DESIGN:
      Computer-based econometric modeling. METHODS: The cost effectiveness of laser
      photocoagulation therapy was compared with the natural course of subfoveal
      choroidal neovascularization. The model applied long-term visual data from
      previous clinical trials, utility analysis (which reflects patient perceptions of
      quality of life associated with a health state), decision analysis with Markov
      modeling, and the economic principles of present value analysis with discounting
      to account for the time value of money. DATABASE: Data from patients eligible for
      treatment of subfoveal choroidal neovascularization obtained by researchers in
      the Macular Photocoagulation Study were used for the analysis. INTERVENTION:
      Modeled laser therapy for subfoveal choroidal neovasacularization in patients
      with age-related macular degeneration. MAIN OUTCOME MEASURE: Cost per quality
      adjusted life-year ($/QALY gained) associated with laser therapy. RESULTS: Laser
      photocoagulation therapy for subfoveal choroidal neovascularization, as compared
      with no treatment, resulted in a mean gain of 0.257 QALYs per treated patient.
      Using a yearly discount rate of 3% to account for the time value of money and
      inflation, the resultant $/QALY gained was $5629. Sensitivity analysis used in
      the cost-effectiveness analysis resulted in a $/QALY gained of $4974 with no
      gained discount rate and $11,633 with a yearly discount rate of 10%. CONCLUSIONS:
      The incremental expense of laser therapy for the treatment of subfoveal choroidal
      neovascularization appears to be highly cost effective. The result, which takes
      into account patient preference-based utility data, compares quite favorably with
      other interventional therapies across different medical specialties.

PMID- 10889116
TI  - Stereotactic radiosurgery of large uveal melanomas with the gamma-knife.
AB  - OBJECTIVE: To present our experience with the Gamma-knife in treating large uveal
      melanomas with stereotactic radiosurgery. DESIGN: Prospective, noncomparative,
      interventional case series. PARTICIPANTS: Fifty-eight patients with unilateral
      uveal melanomas were treated from 1996 through 1999 with stereotactic
      radiosurgery using the Gamma-knife. From these we report the results of 35
      patients who had a follow-up of more than 1 year after irradiation. INTERVENTION:
      Stereotactic radiosurgery with the Gamma-knife. MAIN OUTCOME MEASURES: Tumor
      control, maximum apical tumor height, eye retention rate, and visual acuity.
      RESULTS: In 34 eyes (97%), local tumor control was achieved. The maximum apical
      tumor height decreased from a median of 9.1 mm (95% confidence interval [CI], 3.2
      13.9 mm) before treatment to 6.2 mm (95% CI, 2.1-11.9 mm) at 1 year after
      treatment (P<0.001, paired t test). The tumor volume decreased from a median of
      0.8 cm(3) before treatment to 0.5 cm(3) 1 year after treatment (P<0.001, paired t
      test). Two eyes required enucleation (one radiation failure, one secondary
      glaucoma). The median visual acuity decreased from 20/60 (95% CI, hand movement
      [HM] to 20/20) before treatment to 20/200 (95% CI, HM to 20/30) at 1 year after
      treatment (P = 0.001, paired t test). CONCLUSIONS: Stereotactic radiosurgery
      using the Gamma-knife is an alternative to enucleation in treating large uveal
      melanomas. The visual function may be preserved in selected cases.

PMID- 10889117
TI  - Discussion by evangelos S. Gragoudas, MD

PMID- 10889118
TI  - Comparison of erbium:yttrium-aluminum-garnet-laser vitrectomy and mechanical
      vitrectomy: a clinical study.
AB  - OBJECTIVE: To evaluate the clinical usefulness of the erbium:YAG (yttrium
      aluminum-garnet) laser for vitrectomy and to compare it with a conventional
      mechanical vitrectomy system regarding the intraoperative parameters. DESIGN:
      Prospective, randomized, clinical trial. PARTICIPANTS: Thirty eyes of 30 patients
      underwent vitrectomy, 15 eyes in each group. METHODS: For mechanical vitrectomy,
      a commercially available vitrectomy unit was used. The operating parameters,
      cutting rate (7 Hz = 420 cpm), maximal suction force (300 mmHg), and aspiration
      flow (20 ml/min), were held constant. A newly developed erbium (Er):YAG laser
      unit and handpiece was used for laser vitrectomy with predetermined parameters
      for cutting rate (70 Hz = 4200 cpm), maximal suction force (50 mmHg), and
      aspiration flow (20 ml/min). Surgery parameters were recorded in real time and
      the operation was video recorded. The clinical follow-up time was a minimum of 3
      months (average, 6.2 months; range, 3-9 months). MAIN OUTCOME MEASUREMENTS: The
      surgery time was comparable in both groups. During Er:YAG laser vitrectomy, the
      average suction force was significantly reduced (P< 0.001) compared with that
      during mechanical vitrectomy. The mean-square variation in suction as a measure
      to quantify the forces acting on intraocular structures during surgery was
      significantly smaller in the Er:YAG laser vitrectomy group (P << 0.001).
      CONCLUSIONS: Erbium:YAG laser vitrectomy may provide a semicontinuous procedure.
      This technique minimizes periodical intraoperative forces and movements of
      intraocular structures and may provide, therefore, a safer vitrectomy.

PMID- 10889119
TI  - Nasolacrimal duct obstruction and dacryocystocele associated with a concha
      bullosa mucocele.
AB  - PURPOSE: To describe the rare occurrence of a concha bullosa mucocele producing
      secondary nasolacrimal duct obstruction and dacryocystocele. DESIGN: Case report.
      PARTICIPANT: Forty-two-year-old man with 6-month history of left medial canthal
      mass. INTERVENTION: Clinical evaluation with lacrimal testing, computed
      tomography and surgical exploration, including biopsy, dacryocystorhinostomy, and
      excision/marsupialization of the middle turbinate concha bullosa mucocele were
      performed. RESULTS: The medial canthal mass was confirmed to be a dacryocystocele
      associated with nasolacrimal duct obstruction and bone destruction caused by
      concha bullosa mucocele. CONCLUSIONS: Concha bullosa mucoceles are uncommon and
      even more rarely can produce secondary nasolacrimal duct obstruction and
      dacryocystocele formation. The clinical and radiologic features may mimic a
      lacrimal sac malignancy.

PMID- 10889121
TI  - July 11, 2000

PMID- 10889120
TI  - Ocular histopathologic study of a patient with the T 8993-G point mutation in
      Leigh's syndrome.
AB  - OBJECTIVE: To report the histopathologic findings of eyes from a patient with
      Leigh's syndrome associated with the T 8993-G point mutation in mitochondrial DNA
      (mtDNA). DESIGN: Case report. INTERVENTION: A child with hypotonia, developmental
      delay, persistent lactic acidosis, seizures, and ataxia died of aspiration
      pneumonia at 15 months of age. Analysis of DNA isolated from blood was positive
      for the T to G point mutation at position 8993 in mtDNA, and the proportion of
      mutant genomes was estimated at approximately 95%. The type and distribution of
      abnormalities seen in the brain at autopsy were consistent with those in patients
      with Leigh's syndrome. MAIN OUTCOME MEASURES: The left eye was examined by light
      microscopy, and segments of the right eye were examined by transmission electron
      microscopy. Genetic analysis on DNA isolated from blood was performed. RESULTS:
      Thinning of the nerve fiber and ganglion cell layers was present in the nasal
      aspect of the macula, and mild atrophy of the temporal aspect of the optic nerve
      head and optic nerve was present. Electron microscopic study disclosed numerous
      distended mitochondria in all cells, but particularly in the retinal pigment
      epithelium, nonpigmented ciliary epithelium, and corneal endothelium. CONCLUSION:
      This is a report of the ocular histopathologic findings in Leigh's syndrome with
      the T 8993-G point mutation. The light microscopic findings were similar to those
      of patients with similar features reported previously. In addition,
      ultrastructural abnormalities of mitochondria were present.

PMID- 10889122
TI  - Postscripts from the Post-Coronary Artery Bypass Graft trial: the sustained
      benefit of more aggressive cholesterol lowering and the enigma of low-dose
      anticoagulation.

PMID- 10889123
TI  - Acute and delayed benefits of beta-blockers during coronary intervention: true,
      true and unrelated.

PMID- 10889124
TI  - Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable
      coronary syndromes (OPUS-TIMI 16) trial.
AB  - BACKGROUND: Although intravenous glycoprotein IIb/IIIa inhibitors are beneficial
      in patients with acute coronary syndromes, prolonged oral IIb/IIIa inhibition
      might provide an additional reduction in recurrent events. METHODS AND RESULTS:
      Investigators at 888 hospitals in 29 countries enrolled 10 288 patients with
      acute coronary syndromes, which was defined as ischemic pain at rest within 72
      hours of randomization, associated with positive cardiac markers,
      electrocardiographic changes, or prior cardiovascular disease. Patients received
      aspirin and were randomized to receive, for the duration of the trial, (1) 50 mg
      of orbofiban twice daily (50/50 group), (2) 50 mg of orbofiban twice daily for 30
      days followed by 30 mg of orbofiban twice daily (50/30 group), or (3) a placebo.
      The primary composite end point was death, myocardial infarction, recurrent
      ischemia requiring rehospitalization, urgent revascularization, or stroke. The
      trial was terminated prematurely because of an unexpected increase in 30-day
      mortality in the 50/30 orbofiban group. Mortality through 10 months was 3.7% for
      the placebo group versus 5.1% in the 50/30 group (P=0.008) and 4.5% in the 50/50
      group (P=0.11). There were no differences in the primary end point (22.9%, 23.1%,
      and 22.8%, for the placebo, 50/30, and 50/50 groups, respectively). Major or
      severe bleeding (but not intracranial hemorrhage) was higher with orbofiban; it
      occurred in 2. 0%, 3.7% (P=0.0004), and 4.5% (P<0.0001) of patients,
      respectively. Exploratory subgroup analyses found that patients who underwent
      percutaneous coronary intervention had a lower mortality and a significant
      reduction in the composite end point (P=0.001) with orbofiban. CONCLUSIONS: 
      Fixed-dose orbofiban failed to reduce major cardiovascular events and was
      associated with increased mortality in this broad population of patients with
      acute coronary syndromes; however, a benefit was observed among patients who
      underwent percutaneous coronary intervention.

PMID- 10889125
TI  - Long-term effects on clinical outcomes of aggressive lowering of low-density
      lipoprotein cholesterol levels and low-dose anticoagulation in the post coronary
      artery bypass graft trial. Post CABG Investigators.
AB  - BACKGROUND: The Post Coronary Artery Bypass Graft Trial, designed to compare the
      effects of 2 lipid-lowering regimens and low-dose anticoagulation versus placebo
      on progression of atherosclerosis in saphenous vein grafts of patients who had
      had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol (LDL
      C) levels to <100 mg/dL compared with a moderate reduction to 132 to 136 mg/dL
      decreased the progression of atherosclerosis in grafts. Low-dose anticoagulation
      did not significantly affect progression. METHODS AND RESULTS: Approximately 3
      years after the last trial visit, Clinical Center Coordinators contacted each
      patient by telephone to ascertain the occurrence of cardiovascular events and
      procedures. The National Death Index was used to ascertain vital status for
      patients who could not be contacted. Vital status was established for all but 3
      of 1351 patients. Information on nonfatal events was available for 95% of
      surviving patients. A 30% reduction in revascularization procedures and 24%
      reduction in a composite clinical end point were observed in patients assigned to
      aggressive strategy compared with patients assigned to moderate strategy during
      7.5 years of follow-up, P=0. 0006 and 0.001, respectively. Reductions of 35% in
      deaths and 31% in deaths or myocardial infarctions with low-dose anticoagulation
      compared with placebo were also observed, P=0.008 and 0.003, respectively.
      CONCLUSIONS: -The long-term clinical benefit observed during extended follow-up
      in patients assigned to the aggressive strategy is consistent with the
      angiographic findings of delayed atherosclerosis progression in grafts observed
      during the trial. The apparent long-term benefit of low-dose warfarin remains
      unexplained.

PMID- 10889126
TI  - Cardioprotective effect of prior beta-blocker therapy in reducing creatine kinase
      MB elevation after coronary intervention: benefit is extended to improvement in
      intermediate-term survival.
AB  - BACKGROUND: Both retrospective studies and prospective randomized trials have
      shown that beta-blockers improve survival and reduce the risk of reinfarction in
      patients with myocardial infarction. To evaluate whether beta-blockers exert
      similar protective benefits during and after coronary intervention, we studied
      the incidence of postprocedure creatine kinase (CK)-MB elevation in patients with
      or without prior beta-blocker therapy and its effect on intermediate-term (
      approximately 1 year) survival. METHODS AND RESULTS: We prospectively analyzed
      1675 consecutive patients undergoing coronary intervention; of these patients,
      643 (38.4%) were on beta-blocker therapy before the intervention. The incidence
      of CK-MB elevation after coronary intervention was 13.2% in patients on beta
      blocker therapy before intervention and 22.1% in patients who were not on beta
      blockers (P<0.001). Patients with prior beta-blocker therapy had lower
      persistent/recurrent postprocedure chest pain and lower preprocedure and
      postprocedure heart rates and mean blood pressures compared with patients who
      were not on beta-blockers (P<0.001). Multiple linear regression analysis revealed
      prior beta-blocker therapy as the sole independent factor for lower CK-MB release
      after coronary intervention. During intermediate-term follow-up at 15+/-3 months,
      patients on beta-blocker therapy before intervention had lower mortality rates
      compared with those not on beta-blockers (0.78% versus 1.96%; P=0. 04), although
      the benefit was independent of the reduction in CK-MB release. CONCLUSIONS: Our
      nonrandomized, prospective analysis suggests that prior beta-blocker therapy has
      a cardioprotective effect in limiting CK-MB release after coronary intervention
      and that it is associated with a lower mortality at intermediate-term follow-up.

PMID- 10889127
TI  - Demographic, belief, and situational factors influencing the decision to utilize
      emergency medical services among chest pain patients. Rapid Early Action for
      Coronary Treatment (REACT) study.
AB  - BACKGROUND: Empirical evidence suggests that people value emergency medical
      services (EMS) but that they may not use the service when experiencing chest
      pain. This study evaluates this phenomenon and the factors associated with the
      failure to use EMS during a potential cardiac event. METHODS AND RESULTS:
      Baseline data were gathered from a randomized, controlled community trial (REACT)
      that was conducted in 20 US communities. A random-digit-dial survey documented
      bystander intentions to use EMS for cardiac symptoms in each community. An
      emergency department surveillance system documented the mode of transport among
      chest pain patients in each community and collected ancillary data, including
      situational factors surrounding the chest pain event. Logistic regression
      identified factors associated with failure to use EMS. A total of 962 community
      members responded to the phone survey, and data were collected on 875 chest pain
      emergency department arrivals. The mean proportion of community members intending
      to use EMS during a witnessed cardiac event was 89%; the mean proportion of
      patients observed using the service was 23%, with significant geographic
      differences (range, 10% to 48% use). After controlling for covariates, non-EMS
      users were more likely to try antacids/aspirin and call a doctor and were less
      likely to subscribe to (or participate in) an EMS prepayment plan. CONCLUSIONS:
      The results of this study indicate that indecision, self-treatment, physician
      contact, and financial concerns may undermine a chest pain patient's intention to
      use EMS.

PMID- 10889128
TI  - Hypertriglyceridemic waist: A marker of the atherogenic metabolic triad
      (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men?
AB  - BACKGROUND: The present study tested the hypothesis that simple variables, such
      as waist circumference and fasting plasma triglyceride (TG) concentrations, could
      be used as screening tools for the identification of men characterized by a
      metabolic triad of nontraditional risk factors (elevated insulin and
      apolipoprotein [apo] B and small, dense LDL particles). METHODS AND RESULTS:
      Results of the metabolic study (study 1) conducted on 185 healthy men indicate
      that a large proportion (>80%) of men with waist circumference values >/=90 cm
      and with elevated TG levels (>/=2.0 mmol/L) were characterized by the atherogenic
      metabolic triad. Validation of the model in an angiographic study (study 2) on a
      sample of 287 men with and without coronary artery disease (CAD) revealed that
      only men with both elevated waist and TG levels were at increased risk of CAD
      (odds ratio of 3.6, P<0.03) compared with men with low waist and TG levels.
      CONCLUSIONS: It is suggested that the simultaneous measurement and interpretation
      of waist circumference and fasting TG could be used as inexpensive screening
      tools to identify men characterized by the atherogenic metabolic triad
      (hyperinsulinemia, elevated apo B, small, dense LDL) and at high risk for CAD.

PMID- 10889129
TI  - Vascular endothelial growth factor-A-induced chemotaxis of monocytes is
      attenuated in patients with diabetes mellitus: A potential predictor for the
      individual capacity to develop collaterals.
AB  - BACKGROUND: Vascular endothelial growth factor-A (VEGF-A) acts on endothelial
      cells and monocytes, 2 cell types that participate in the angiogenic and
      arteriogenic process in vivo. Thus far, it has not been possible to identify
      differences in individual responses to VEGF-A stimulation because of the lack of
      an ex vivo assay. METHODS AND RESULTS: We report a chemotaxis assay using
      isolated monocytes from individual diabetic patients and from healthy, age
      matched volunteers. The chemotactic response of individual monocyte preparations
      to VEGF-A, as mediated via Flt-1, was quantitatively assessed using a modified
      Boyden chamber. Although the migration of monocytes from healthy volunteers could
      be stimulated with VEGF-A (1 ng/mL) to a median of 148.4% of the control value
      (25th and 75th percentiles, 136% and 170%), monocytes from diabetic patients
      could not be stimulated with VEGF-A (median, 91.1% of unstimulated controls; 25th
      and 75th percentiles, 83% and 98%; P<0.0001). In contrast, the response of
      monocytes to the chemoattractant formylMetLeuPhe remained intact in diabetic
      patients. The VEGF-A-inducible kinase activity of Flt-1, as assessed by in vitro
      kinase assays, remained intact in monocytes from diabetic patients. Moreover, the
      serum level of VEGF-A, as assessed by immunoradiometric assay, was significantly
      elevated in diabetic patients. CONCLUSIONS: The cellular response of monocytes to
      VEGF-A is attenuated in diabetic patients because of a downstream signal
      transduction defect. These data suggest that monocytes are important in
      arteriogenesis and that their ability to migrate might be critical to the
      arteriogenic response. Thus, we resolved a fundamental mechanism involved in the
      problem of impaired collateral formation in diabetic patients.

PMID- 10889130
TI  - Low-density lipoprotein postsecretory modification, monocyte function, and
      circulating adhesion molecules in type 2 diabetic patients with and without
      macrovascular complications: the effect of alpha-tocopherol supplementation.
AB  - BACKGROUND: Although diabetes confers an increased propensity toward accelerated
      atherogenesis, data are lacking on monocyte activity in type 2 diabetic patients
      with (DM2-MV) and without (DM2) macrovascular disease compared with control
      subjects. Thus, we tested whether (1) postsecretory modifications of LDL
      (glycation and oxidation), monocyte proatherogenic activity, and circulating
      levels of soluble cell adhesion molecules (sCAMs) are more pronounced in DM2-MV
      than in DM2 and control subjects and (2) RRR-alpha-tocopherol (AT) therapy, 1200
      IU/d for 3 months, has a similar effect in the 3 groups (n=25 per group). METHODS
      AND RESULTS: Although LDL glycation was increased in both diabetic groups
      compared with control subjects, AT therapy had no significant effect on
      glycation. AT therapy significantly decreased LDL oxidizability in all 3 groups.
      Diabetic monocytes released significantly more superoxide anion (O(2)(-)) and
      interleukin-1beta (IL-1beta) and exhibited greater adhesion to endothelium than
      control subjects. AT therapy significantly decreased the release of O(2)(-), IL
      1beta, tumor necrosis factor-alpha, and monocyte-endothelium adhesion in all 3
      groups. There was no significant difference between the 2 diabetic groups for any
      of the above parameters. sICAM levels were significantly elevated in both
      diabetic groups compared with controls. AT therapy resulted in a significant
      decrease in sCAMs. CONCLUSIONS: This is the first demonstration of increased IL
      1beta secretion and increased adhesion of monocytes to endothelium from
      normotriglyceridemic diabetic subjects and of decreased monocyte activity and
      sCAMs with AT therapy in diabetic subjects with and without macrovasculopathy.

PMID- 10889131
TI  - Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene is
      not associated with restenosis after coronary stent placement.
AB  - BACKGROUND: The renin-angiotensin system is thought to play a role in coronary
      thrombosis and restenosis. Plasma angiotensin I-converting enzyme (ACE) activity
      is associated with an insertion/deletion polymorphism in the gene coding for ACE.
      The objective of this study was to test the hypothesis that the D allele of the
      ACE gene is associated with a higher risk for restenosis after coronary stent
      placement. METHODS AND RESULTS: This prospective study included 1850 consecutive
      patients with coronary artery disease who underwent intracoronary stent
      implantation. The adverse clinical events recorded were death, myocardial
      infarction, and target vessel revascularization. The primary end point of the
      study was restenosis (>/=50% diameter stenosis at follow-up angiography performed
      in 84% of the patients). The secondary end point was clinical outcome 1 year
      after the procedure. The restenosis rate at the 6-month angiographic follow-up
      was 32.8% in patients with the II genotype, 34.0% for patients with the ID
      genotype, and 31.2% for patients with the DD genotype (P=0.62). One-year event
      free survival was 77.7% in patients with genotype II, 75.2% in patients with
      genotype ID, and 75.5% in patients with genotype DD (P=0.54). The lack of
      association was also present in the subgroup of patients with a low risk for
      restenosis: the restenosis rate was 21.7% in II carriers, 23.4% in ID carriers,
      and 19.7% in DD carriers (P=0.83). CONCLUSIONS: The ACE DD genotype or D allele
      does not influence the 1-year clinical and angiographic outcome of patients
      undergoing coronary stent placement. These data suggest that routine
      determination of the ACE genotype may not help identify patients who are at a
      higher risk of thrombotic and restenotic events after coronary stent placement.

PMID- 10889132
TI  - Renal function, neurohormonal activation, and survival in patients with chronic
      heart failure.
AB  - BACKGROUND: Because renal function is affected by chronic heart failure (CHF) and
      it relates to both cardiovascular and hemodynamic properties, it should have
      additional prognostic value. We studied whether renal function is a predictor for
      mortality in advanced CHF, and we assessed its relative contribution compared
      with other established risk factors. In addition, we studied the relation between
      renal function and neurohormonal activation. METHODS AND RESULTS: The study
      population consisted of 1906 patients with CHF who were enrolled in a recent
      survival trial (Second Prospective Randomized study of Ibopamine on Mortality and
      Efficacy). In a subgroup of 372 patients, plasma neurohormones were determined.
      The baseline glomerular filtration rate (GFR(c)) was calculated using the
      Cockroft Gault equation. GFR(c) was the most powerful predictor of mortality; it
      was followed by New York Heart Association functional class and the use of
      angiotensin-converting enzyme inhibitors. Patients in the lowest quartile of
      GFR(c) values (<44 mL/min) had almost 3 times the risk of mortality (relative
      risk, 2. 85; P<0.001) of patients in the highest quartile (>76 mL/min). Impaired
      left ventricular ejection fraction (LVEF) was only modestly predictive (P=0.053).
      GFR(c) was inversely related with N-terminal atrial natriuretic peptide (ANP; r=
      0.53) and, to a lesser extent, with ANP itself (r=-0.35; both P<0.001).
      CONCLUSIONS: Impaired renal function (GFR(c)) is a stronger predictor of
      mortality than impaired cardiac function (LVEF and New York Heart Association
      class) in advanced CHF, and it is associated with increased levels of N-terminal
      ANP. Moreover, impaired renal function was not related to LVEF, which suggests
      that factors other than reduced cardiac output are causally involved.

PMID- 10889133
TI  - Independent prognostic value of cardiac troponin T in patients with confirmed
      pulmonary embolism.
AB  - BACKGROUND: Cardiac troponin T (cTnT) is a sensitive and specific marker,
      allowing the detection of even minor myocardial cell injury. In patients with
      severe pulmonary embolism (PE), myocardial ischemia may lead to progressive right
      ventricular dysfunction. It was therefore the purpose of this study to test the
      presence of cTnT and its prognostic implications in patients with confirmed PE.
      METHODS AND RESULTS: Fifty-six consecutive patients with confirmed PE were
      enrolled in this prospective study. PE was confirmed by pulmonary angiography,
      lung scan, or echocardiography and subsidiary analyses. Severity of PE was
      assessed by a clinical scoring system, and cTnT was measured within 12 hours
      after admission. cTnT was elevated (>/=0.1 microg/L) in 18 (32%) patients with
      massive and moderate PE but not in patients with small PE. In-hospital death
      (odds ratio 29. 6, 95% CI 3.3 to 265.3), prolonged hypotension and cardiogenic
      shock (odds ratio 11.4, 95% CI 2.1 to 63.4), and need for resuscitation (odds
      ratio 18.0, 95% CI 2.6 to 124.3) were more prevalent in patients with elevated
      cTnT. cTnT-positive patients more often needed inotropic support (odds ratio
      37.6, 95% CI 5.8 to 245.6) and mechanical ventilation (odds ratio 78.8, 95% CI
      9.5 to 653.2). After adjustment, cTnT remained an independent predictor of 30-day
      mortality (odds ratio 15.2, 95% CI 1.22 to 190.4). CONCLUSIONS: cTnT may improve
      risk stratification in patients with PE and may aid in the identification of
      patients in whom a more aggressive therapy may be warranted.

PMID- 10889134
TI  - Diastolic biomechanics in normal infants utilizing MRI tissue tagging.
AB  - BACKGROUND: Most of what is known about diastolic function in normal infants is
      derived from flow and pressure measurements. Little is known about regional
      diastolic strain and wall motion. METHODS AND RESULTS: Magnetic resonance tissue
      tagging was performed in 11 normal infants to determine regional diastolic strain
      and wall motion. Tracking diastolic motion of the intersection points and finite
      strain analysis yielded regional rotation, radial displacement, and E(1) and E(2)
      strains at 3 short-axis levels (significance was defined as P<0.05). E(2)
      "circumferential lengthening" strains were significantly greater at the lateral
      wall, regardless of short-axis level, whereas E(1) "radial thinning" strains were
      similar in all wall regions at all short-axis levels. In general, no differences
      were noted in strain dispersion within a wall region or in endocardial/epicardial
      strain at all short-axis levels. At all short-axis levels, septal radial motion
      was significantly less than in other wall regions. No significant differences in
      radial wall motion between short-axis levels were noted. Rotation was
      significantly greater at the apical short-axis level in all wall regions than in
      other short-axis levels, and it was clockwise. At the atrioventricular valve,
      septal and anterior walls rotated slightly clockwise, whereas the lateral and
      inferior walls rotated counterclockwise. CONCLUSIONS: Diastolic biomechanics in
      infants are not homogeneous. The lateral walls are affected most by strain, and
      the septal walls undergo the least radial wall motion. Apical walls undergo the
      most rotation. These normal data may help in the understanding of diastolic
      dysfunction in infants with congenital heart disease.

PMID- 10889135
TI  - Shear stress downregulation of platelet-derived growth factor receptor-beta and
      matrix metalloprotease-2 is associated with inhibition of smooth muscle cell
      invasion and migration.
AB  - BACKGROUND: After endovascular injury, smooth muscle cells (SMCs) may be exposed
      to hemodynamic shear stress (SS), and these forces modulate neointima
      accumulation. The effect of SS on SMC migration and invasion is unknown, and it
      was examined in the present study. METHODS AND RESULTS: Bovine aortic SMCs were
      exposed to laminar SS of 12 dyne/cm(2) for 3 (SS3) or 15 (SS15) hours; control
      (C3 and C15) SMCs were kept under static conditions. Platelet-derived growth
      factor (PDGF)-BB-directed SMC migration and invasion were evaluated by a modified
      Boyden chamber assay with filters coated with either gelatin or reconstituted
      basement membrane proteins (Matrigel), respectively. SS15 inhibited both SMC
      migration and invasion (P<0.0001). There was no significant difference between
      SS3 and C3 cells. Media conditioned with SS15 cells exhibited a reduction in
      matrix metalloprotease-2 (MMP-2) by zymography and Western analysis. Northern
      blot analysis revealed no effect of SS15 on MMP-2 mRNA. In contrast, SS15
      decreased MMP-2 activator and membrane-type MMP (MT-MMP or MMP-14) mRNA and
      protein. Furthermore, SS15 decreased PDGF receptor-beta (PDGF-Rbeta) mRNA and
      protein (P<0.05), and the SS-dependent decrease in PDGF-BB-directed cell
      migration was rescued by overexpressing PDGF-Rbeta. CONCLUSIONS: SS inhibits SMC
      migration and invasion via diminished PDGF-Rbeta expression. This effect of SS is
      associated with decreased MMP-2 secretion and MT-MMP downregulation.

PMID- 10889136
TI  - Selective targeting of gene transfer to vascular endothelial cells by use of
      peptides isolated by phage display.
AB  - BACKGROUND: Gene transfer to vascular cells is a highly inefficient and
      nonselective process, defined by the lack of specific cell-surface receptors for
      both nonviral and viral gene delivery vectors. METHODS AND RESULTS: We used
      filamentous phage display to isolate a panel of peptides that have the ability to
      bind selectively and efficiently to quiescent human umbilical vein endothelial
      cells (HUVECs) with reduced or negligible binding to nonendothelial cells,
      including vascular smooth muscle cells and hepatocytes. By direct biopanning on
      HUVECs and a second approach involving preclearing steps before panning on
      HUVECs, we isolated and sequenced 140 individual phages and identified 59
      peptides. We selected 7 candidates for further investigation by secondary
      screening of homogeneous phages on a panel of cell types. Using adenovirus
      mediated gene transfer as a model gene delivery system, we cloned the peptide
      SIGYPLP and the positive control peptide KKKKKKK upstream of the S11e single
      chain Fv ("adenobody") directed against the knob domain of the adenovirus to
      create fusion proteins. Adenovirus-mediated gene transfer via fiber-dependent
      infection was blocked with S11e, whereas inclusion of the KKKKKKK peptide
      retargeted gene transfer. The peptide SIGYPLP, however, retargeted gene delivery
      specifically to endothelial cells with a significantly enhanced efficiency over
      nontargeted adenovirus and without transduction of nontarget cells. CONCLUSIONS:
      Our study demonstrates the feasibility of using small, novel peptides isolated
      via phage display to target gene delivery specifically and efficiently to HUVECs
      and highlights their use for retargeting both viral and nonviral gene transfer to
      vascular endothelial cells for future clinical applications.

PMID- 10889137
TI  - Ultrasound imaging-guided noninvasive ultrasound thrombolysis: preclinical
      results.
AB  - BACKGROUND: Catheter-based therapeutic ultrasound thrombolysis was recently shown
      to be effective and safe. The purpose of this work was to study the safety and
      efficacy of external high-intensity focused ultrasound thrombolysis guided by
      ultrasound imaging in experimental settings. METHODS AND RESULTS: A therapeutic
      transducer was constructed from an acoustic lens and integrated with an
      ultrasound imaging transducer. In vitro clots were inserted into bovine arterial
      segments and sonicated under real-time ultrasound imaging guidance in a water
      tank. With pulsed-wave (PW) ultrasound, the total sonication time correlated with
      thrombolysis efficiency (r(2)=0.7666). A thrombolysis efficiency of 91% was
      achieved with optimal PW parameters (1:25 duty cycle, 200-micros pulse length) at
      an intensity (I(spta)) of >35+/-5 W/cm(2). Ultrasound imaging during sonication
      showed the cavitation field as a spherical cloud of echo-dense material. Within
      <2 minutes, the vessel lumen evidenced neither residual clot nor damage to the
      arterial wall. On serial filtration, 93+/-1% of the lysed clot became
      subcapillary in size (<8 microm). In vitro safety studies, however, showed
      arterial damage when an I(spta) of 45 W/cm(2) was used for periods of >/=300
      seconds. CONCLUSIONS: External high-intensity focused ultrasound thrombolysis
      using optimal PW parameters for periods of </=300 seconds appears to be a safe
      and effective method to induce thrombolysis. The procedure can be guided by
      ultrasound imaging, thereby allowing the monitoring of therapy.

PMID- 10889138
TI  - Potential contribution of a novel antifibrotic factor, hepatocyte growth factor,
      to prevention of myocardial fibrosis by angiotensin II blockade in
      cardiomyopathic hamsters.
AB  - BACKGROUND: Because hepatocyte growth factor (HGF) prevented and/or regressed
      fibrosis in liver and pulmonary injury models, HGF may play an important role in
      the pathogenesis of fibrotic cardiovascular disease. Because angiotensin (Ang) II
      significantly decreased local HGF production, we performed (1) in vitro
      experiments using fibroblasts and (2) administration of an ACE inhibitor
      (temocapril) and an Ang II type 1 receptor antagonist (CS-866) to cardiomyopathic
      hamsters. METHODS AND RESULTS: In human fibroblasts, HGF significantly increased
      the production of matrix metalloprotease-1 (MMP-1) and urokinase plasminogen
      activator, whereas HGF also significantly attenuated the reduction of MMP-1
      activity induced by Ang II. In contrast, HGF significantly decreased transforming
      growth factor (TGF)-beta mRNA stimulated by Ang II, whereas HGF also decreased
      basal TGF-beta protein level without affecting growth. Similarly, in rat cardiac
      fibroblasts, HGF inhibited the expression and production of TGF-beta, whereas HGF
      upregulated its specific receptor, c-met. Conversely, in vivo experiments
      revealed that administration of temocapril and CS-866 to cardiomyopathic hamsters
      resulted in a significant decrease in fibrotic area and increase in cardiac HGF
      concentration and mRNA (P<0.01), whereas cardiac concentration and mRNA of HGF
      were significantly decreased in cardiomyopathic hamsters. In contrast, mRNA
      expression of collagen III was markedly decreased by treatment with temocapril
      and CS-866. CONCLUSIONS: Here, we demonstrated that Ang II blockade prevented
      myocardial fibrosis in the cardiomyopathic hamster, accompanied by a significant
      increase in cardiac HGF. Overall, increase in local HGF expression may
      participate in the prevention of myocardial injury by Ang II blockade through its
      antifibrotic action.

PMID- 10889139
TI  - Reverse remodeling of cardiac myocyte hypertrophy in hypertension and failure by
      targeting of the renin-angiotensin system.
AB  - BACKGROUND: ACE inhibitors (ACEIs) and angiotensin II type 1 (AT(1)) receptor
      blockers are effective in reducing left ventricular mass in hypertension and
      heart failure. However, the ability of these drugs to reverse excessive myocyte
      lengthening and transverse growth in heart failure is unknown. METHODS AND
      RESULTS: L-158,809 (an AT(1) blocker; AT(1)), enalapril (an ACEI), and
      hydralazine (a vasodilator) were administered to spontaneously hypertensive heart
      failure rats between 6 and 10 months of age (early treatment) and between 18 and
      22 months of age (late treatment). After 4 months of treatment, hemodynamics and
      chamber dimensions were collected before left ventricular myocyte isolation and
      subsequent analysis of myocyte shape. Each drug reduced systolic blood pressures
      to normal values. In the early and late studies, the ACEI reduced myocyte volume.
      Myocyte length was also reduced in the late study. However, the AT(1) was most
      effective in reversing myocyte dimensions to near-normal values in both studies.
      Hydralazine was ineffective in reducing cell size but arrested progression of
      myocyte lengthening in the late study. Changes in myocyte shape reflected
      alterations in chamber dimensions and wall thickness. CONCLUSIONS: Reversal of
      myocyte hypertrophy was produced in hypertensive/heart failure rats with an
      AT(1). The ACEI was effective but to a lesser extent. Results indicate that it is
      possible to significantly reverse myocyte remodeling pharmacologically even if
      therapy is initiated near the onset of failure. Further work is needed to
      determine whether similar results can be obtained in humans.

PMID- 10889140
TI  - Widening of the excitable gap during pharmacological cardioversion of atrial
      fibrillation in the goat: effects of cibenzoline, hydroquinidine, flecainide, and
      d-sotalol.
AB  - BACKGROUND: Previous studies suggest that the antifibrillatory action of class I
      and III drugs is due to prolongation of the atrial wavelength. The aim of the
      present study was to directly evaluate the electrophysiological action of
      antifibrillatory drugs in a goat model of chronic atrial fibrillation (AF).
      METHODS AND RESULTS: Six goats were instrumented with multiple atrial electrodes,
      and sustained AF was induced by electrical remodeling. During sustained AF, the
      effects of intravenous infusion of cibenzoline, hydroquinidine, flecainide, and d
      sotalol on AF cycle length (AFCL), refractory period (RP(AF)), conduction
      velocity (CV(AF)), pathlength (PL(AF)), wavelength (WL(AF)), temporal (AFCL
      RP(AF)), and spatial (PL(AF)-WL(AF)) excitable gap were studied. The RP(AF) was
      measured by determining the earliest moment at which single stimuli could capture
      the fibrillating atria. CV(AF) was measured during regional entrainment of AF.
      Contrary to our expectation, cardioversion of AF could not be attributed to
      prolongation of WL(AF). Hydroquinidine and d-sotalol did not affect WL(AF)
      significantly, whereas cibenzoline and flecainide even shortened WL(AF) by 18%
      and 36%, respectively. PL(AF) was increased by hydroquinidine and d-sotalol by
      30%, whereas cibenzoline and flecainide did not prolong PL(AF). The only
      parameter that correlated consistently with cardioversion of AF was a widening of
      the temporal excitable gap (cibenzoline 176%, hydroquinidine 105%, flecainide
      86%, d-sotalol 88%). CONCLUSIONS: Pharmacological cardioversion of AF cannot be
      explained by prolongation of WL(AF). An alternative explanation for the
      antifibrillatory effect of class I and III drugs may be a widening of the
      temporal excitable gap.

PMID- 10889141
TI  - Percutaneous embolization of thoracic duct injury.

PMID- 10889142
TI  - Right ventricular myxoma obstructing the right ventricular outflow tract.

PMID- 10889143
TI  - Effects of walking on coronary heart disease in elderly men.

PMID- 10889144
TI  - Risk of cocaine-induced myocardial infarction during sport.

PMID- 10889145
TI  - Late results of percutaneous balloon mitral valvuloplasty: the Chinese
      experience.

PMID- 10889146
TI  - Is the corrected TIMI frame count an independent predictor of adverse outcome?

PMID- 10889147
TI  - Coronary calcium does not accurately predict near-term future coronary events in
      high-risk adults.

PMID- 10889148
TI  - David and Goliath: discovery in the industrial age of science.

PMID- 10889149
TI  - Atrophy and intestinal metaplasia one year after cure of H. pylori infection: a
      prospective, randomized study.
AB  - BACKGROUND & AIMS: Helicobacter pylori-infected gastric mucosa evolves through
      stages of chronic gastritis, intestinal metaplasia (IM), glandular atrophy (GA),
      and dysplasia before carcinoma develops. We studied if H. pylori eradication
      would alter the course of premalignant histologic changes in the stomach.
      METHODS: Volunteers from the Yantai County in China underwent upper endoscopy
      with biopsy specimens obtained from the antrum and corpus. H. pylori-infected
      subjects were randomized to receive either a 1-week course of omeprazole,
      amoxicillin, and clarithromycin (OAC) or placebo. At 1 year, endoscopies with
      biopsies were repeated. RESULTS: A total of 587 H. pylori-infected subjects were
      randomized to OAC (n = 295) and placebo (n = 292). At 1 year, H. pylori was
      eradicated in 226 subjects assigned to OAC. In the placebo group, 245 patients
      remained H. pylori infected. Analysis of paired samples obtained from the same
      patients showed that acute and chronic gastritis decreased in both the antrum and
      corpus after H. pylori eradication (P<0.001) and activity of IM decreased in
      antrum (P = 0.014). In the H. pylori-infected group, antral biopsy specimens had
      more pronounced acute gastritis (P = 0.01), whereas corpus specimens showed
      increased acute and chronic gastritis (P<0.001) and a marginal increase in GA (P
      = 0.052). When histologic changes were compared between the 2 groups, decrease in
      acute and chronic gastritis was more frequent after H. pylori eradication
      (P<0.001) but changes in IM were similar. In the H. pylori-infected group,
      increase in GA was seen in the corpus (P = 0.01). CONCLUSIONS: At 1 year, H.
      pylori eradication is beneficial in preventing progression of pathologic changes
      of the gastric mucosa.

PMID- 10889150
TI  - Surrogate markers of intestinal inflammation are predictive of relapse in
      patients with inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Prediction of relapse of inflammatory bowel disease has
      important implications for therapeutic strategies. We assessed whether
      measurement of intestinal permeability and inflammation could predict relapse of
      inflammatory bowel disease (IBD). METHODS: Forty-three patients with Crohn's
      disease (CD) and 37 with ulcerative colitis (UC) in clinical remission provided a
      stool sample to be assayed for calprotectin (a neutrophil-specific marker), and
      patients with CD additionally underwent a small intestinal permeability test.
      Relapse was defined using clinical disease activity indices. RESULTS: Twenty-five
      (58%) patients with CD and 19 (51%) with UC had a relapse over the 12-month
      period. Median calprotectin levels in the relapse groups (122 mg/L for CD, 123
      mg/L for UC; normal <10 mg/L) differed significantly (P<0.0001) from those of the
      nonrelapse groups (41.5 mg/L for CD, 29.0 mg/L for UC). At 50 mg/L, the
      sensitivity and specificity of calprotectin for predicting relapse in all
      patients with IBD were 90% and 83%, respectively. Permeability in the CD patients
      who relapsed (median, 0.075; normal <0.04) differed significantly (P = 0. 004)
      from that in the nonrelapse group (median, 0.038). At the level of 0.05, the
      sensitivity and specificity of permeability in predicting relapse were 84% and
      61%, respectively. CONCLUSIONS: Fecal calprotectin predicts clinical relapse of
      disease activity in patients with CD and UC, whereas small intestinal
      permeability is a useful predictor of relapse in patients with small intestinal
      CD.

PMID- 10889151
TI  - Identification of a novel bacterial sequence associated with Crohn's disease.
AB  - BACKGROUND & AIMS: Enteric microorganisms are implicated in the pathogenesis of
      Crohn's disease (CD), but no clear bacterial or viral species has been
      identified. In this study, representational difference analysis (RDA) was used to
      isolate DNA segments preferentially abundant in lamina propria mononuclear cells
      of lesional mucosa vs. adjacent uninvolved mucosa. METHODS: Two RDA-derived
      microbial sequences were isolated (I1 and I2) and identified as novel homologues
      of the ptxR and tetR bacterial transcription-factor families. RESULTS:
      Quantitative competitive polymerase chain reaction of paraffin-embedded
      intestinal specimens from 212 patients showed that I2 DNA was present in many CD
      colonic lesions (43%), but was infrequent in other colonic specimens (9% of
      ulcerative colitis lesions and 5% of non-inflammatory bowel disease diseases;
      P<0.0001). I2 was prevalent in ileal specimens, regardless of disease status (43%
      54%). Enzyme-linked immunosorbent assay analysis of 150 individuals with an I2
      glutathione-S-transferase fusion protein showed frequent immunoglobulin A
      seroreactivity in CD (54% of patients), but infrequent seroreactivity in patients
      with ulcerative colitis, other inflammatory enteric diseases, or normals (10%,
      19%, and 4%, respectively; P<0.001 to 0.00001). CONCLUSIONS: These findings
      relate CD to a novel lesion-localized and immunologically associated bacterial
      sequence, suggesting that the microorganism expressing the I2 gene product may be
      related to CD pathogenesis.

PMID- 10889152
TI  - Residual chloride secretion in intestinal tissue of deltaF508 homozygous twins
      and siblings with cystic fibrosis. The European CF Twin and Sibling Study
      Consortium.
AB  - BACKGROUND & AIMS: Cholinergic stimulation of chloride secretion is impaired in
      the intestines of patients with cystic fibrosis (CF). However, intestinal
      chloride secretion has been observed in patients with mild CF mutations. The aim
      of this study was to investigate residual Cl(-) secretion in the intestine of
      DeltaF508 homozygous CF patients, and examine the contribution of cystic fibrosis
      transmembrane conductance regulator (CFTR) and alternative Cl(-) conductances.
      Twins and siblings with identical CFTR genotypes were investigated to determine
      the impact of factors other than CFTR on chloride secretion. METHODS: Chloride
      secretion in rectal tissue was investigated by applying Ca(2+) and adenosine
      3',5'-cyclic monophosphate (cAMP)-linked agonists before and after the inhibition
      of alternative Cl(-) conductances with 4,4'-diisothiocyanostilbene-2, 2'
      disulfonic acid (DIDS). RESULTS: cAMP-mediated Cl(-) secretion was observed in
      73% of patients, and 20% showed DIDS-sensitive Ca(2+)-activated Cl(-) secretion.
      This DIDS-sensitive alternative chloride conductance was seen only in CF patients
      who also responded to cAMP agonists. Chloride secretion was more concordant
      within monozygous twins than within dizygous pairs. CONCLUSIONS: These results
      suggest the presence of CFTR-mediated Cl(-) secretion in a subgroup of patients,
      implying that a portion of deltaF508 CFTR can be processed in vivo and function
      as a chloride channel in the apical membrane of intestinal cells. Moreover, a
      considerable number of deltaF508 homozygous patients express chloride
      conductances other than CFTR in their intestinal epithelia.

PMID- 10889153
TI  - Recombinant human neurotrophic factors accelerate colonic transit and relieve
      constipation in humans.
AB  - BACKGROUND & AIMS: The aim of this study was to assess the effects of recombinant
      human brain-derived neurotrophic factor (r-metHuBDNF) and recombinant human
      neurotrophic factor 3 (r-metHuNT-3) on gastrointestinal motor functions in
      healthy people and in patients with constipation. METHODS: Gastrointestinal and
      colonic transit was measured by scintigraphy before and after 2 weeks of
      treatment. Daily diaries documented symptoms over 6 weeks before, during, and
      after treatment. In a randomized study of healthy subjects, 40 received 100
      microg/kg r-metHuBDNF or placebo subcutaneously (SC) daily. In a separate study,
      8 healthy subjects and 8 patients with constipation received 300 microg/kg r
      metHuNT-3 SC thrice weekly. RESULTS: r-met-HuBDNF accelerated overall and
      proximal colonic emptying (P<0.05) in health. r-metHuNT-3 accelerated overall
      colonic transit in health and constipation (all P<0.05) and gastric and small
      bowel transit (both P<0.05) in health. r-metHuBDNF tended to increase stool
      frequency compared with placebo in health (P = 0.09). r-metHuNT-3 increased stool
      frequency (P = 0.05) and facilitated passage of stool (P < 0.01) in constipated
      patients. The effects on stool frequency started within 3 days of the beginning
      of neurotrophin administrations and lasted up to 5 days after treatment ended. r
      metHu neurotrophic factors were well tolerated, although half of the participants
      in the 2 studies developed injection site reactions or paresthesiae. CONCLUSIONS:
      Exogenous neurotrophic factors stimulate human gut motility in health and
      constipation.

PMID- 10889154
TI  - Gq-linked NK(2) receptors mediate neurally induced contraction of human sigmoid
      circular smooth muscle.
AB  - BACKGROUND & AIMS: Because tachykinins have been identified as neurotransmitters
      in the guinea pig colon and human ileum, we examined a possible role of
      tachykinin receptors and neurokinin (NK) A in neurally induced contraction of
      human sigmoid colon circular muscle. METHODS: Muscle strips were stimulated
      electrically for 10 seconds. Single cells were isolated by enzymatic digestion
      and permeabilized by saponin. [(35)S]GTPgammaS binding was assayed with or
      without NKA for 5 minutes. Intracellular Ca(2+) was measured using Fura 2.
      RESULTS: In the presence of 100 micromol/L L-NNA, 100 micromol/L atropine did not
      affect electrical field stimulation (EFS)-induced contraction. A peptide NK(2)
      receptor antagonist (NK-2ra) but not an NK(1) antagonist FK888 (1 micromol/L)
      eliminated EFS-induced contraction. NKA-induced contraction in muscle strips and
      single cells was virtually abolished by NK-2ra, but not by FK888. In
      permeabilized cells, contraction was blocked by Gq-protein antibodies, but not by
      other G-protein antibodies, suggesting that NKA activates Gq, which was confirmed
      by a [(35)S]GTPgammaS binding assay. NKA-induced contraction and increase in
      cytosolic Ca(2+) were abolished by depletion of intracellular Ca(2+) stores.
      CONCLUSIONS: Tachykinins may be the main excitatory neurotransmitters in human
      sigmoid circular muscle. NKA activates Gq-linked NK(2) receptors, which cause
      Ca(2+) release, followed by contraction.

PMID- 10889155
TI  - Impaired activation of cytosolic phospolipase A(2) in inflamed canine colonic
      circular muscle.
AB  - BACKGROUND & AIMS: Arachidonic acid (AA) is a critical second messenger in
      several cell types. We examined whether cholinergic AA acts as a second messenger
      in contraction of colonic circular muscle cells and if this role is altered by
      inflammation. METHODS: The experiments were performed on single dispersed cells.
      AA release was measured by high-performance liquid chromatography. Escherichia
      coli membranes labeled with (3)H-AA were used as a substrate for determining
      phospholipase A(2) (PLA(2)) activity, and Western immunoblotting for protein
      expression. RESULTS: Acetylcholine and the PLA(2) activator melittin induced cell
      contractions and AA release. Both effects were inhibited by the PLA(2) inhibitor
      ONO-RS-082. Cytosolic and membrane PLA(2) activities increased in response to
      acetylcholine. These were blocked by ONO-RS-082 and cytosolic PLA(2) 100
      kilodalton antibody, but not by dithiothreitol, a secretory PLA(2) inhibitor.
      Acetylcholine- and melittin-stimulated release of AA and their contractile
      response were attenuated in inflamed cells. Immunoblotting indicated that the
      protein expression of cPLA(2) was suppressed during inflammation. CONCLUSIONS: AA
      acts as a second messenger in muscarinic receptor-activated contractions of
      colonic circular muscle cells. cPLA(2) is the primary enzyme that releases AA in
      these cells; its expression as well as activation are significantly attenuated by
      inflammation. The attenuated release of AA may partly account for the inhibition
      of colonic circular muscle tone and phasic contractions observed during
      inflammation.

PMID- 10889156
TI  - Orphanin FQ, but not dynorphin A, accelerates colonic transit in rats.
AB  - BACKGROUND & AIMS: The endogenous opiate receptor-like 1 ligand, orphanin FQ
      (OFQ), which structurally resembles dynorphin A, has been identified. We
      investigated the mechanism of action of OFQ in the colon and compared it with
      that of dynorphin A in vivo. METHODS: Colonic contractions were recorded via
      miniature force transducers implanted on the serosal surface of the rat colon.
      RESULTS: Intravenous administration of OFQ (0.01-3 nmol/kg) induced contractions
      in the rat colon in a dose-dependent manner. Colonic contractions induced by OFQ
      were not affected by extrinsic denervation but abolished by tetrodotoxin.
      Continuous infusion of OFQ (1 nmol x kg(-1) x min(-1)) and dynorphin A (100 nmol
      x kg(-1) x min(-1)) induced similar phasic contractions in the proximal colon.
      However, the contractile activity induced by the 2 peptides differed
      significantly in the mid and distal colon. Giant contractions induced by OFQ
      infusion migrated from the mid to distal colon. In contrast, dynorphin A evoked
      simultaneous contractions throughout the entire colon, which did not migrate
      aborally. Subcutaneous administration of OFQ (1-3 nmol/kg) accelerated colonic
      transit, whereas dynorphin A (30-100 nmol/kg) delayed colonic transit.
      CONCLUSIONS: The results show that OFQ accelerates colonic transit by promoting
      migrating colonic contractions in rats.

PMID- 10889157
TI  - Regulation of guinea pig intestinal peristalsis by endogenous endothelin acting
      at ET(B) receptors.
AB  - BACKGROUND & AIMS: Endothelins are expressed in many enteric neurons of the gut.
      Because activation of endothelin ET(A) and ET(B) receptors is known to alter
      intestinal muscle activity, the effect of ET(A) and ET(B) receptor agonists and
      antagonists on propulsive peristalsis was examined. METHODS: Repetitive
      peristalsis in fluid-perfused segments of the guinea pig isolated small intestine
      was elicited by a rise of the intraluminal pressure and recorded via the pressure
      changes generated by the peristaltic waves. RESULTS: Endothelin 1 (0.3-10 nmol/L
      added to the organ bath) stimulated peristalsis as shown by a decrease in the
      pressure threshold at which peristaltic waves were triggered, whereas the
      endothelin analog sarafotoxin 6c (0.3-10 nmol/L) inhibited peristalsis as
      reflected by an increase in the pressure threshold. The ET(A) receptor antagonist
      BQ-123 (3 micromol/L) converted the properistaltic action of endothelin 1 to an
      antiperistaltic action, whereas the ET(B) receptor antagonist BQ-788 (3
      micromol/L) prevented the antiperistaltic action of sarafotoxin 6c. BQ-788, but
      not BQ-123, facilitated peristalsis on its own. Additional experiments indicated
      that the properistaltic action of endothelin 1 is mediated by enteric neurons,
      whereas the peristaltic motor effects of sarafotoxin 6c and BQ-788 are caused by
      a direct action on the muscle. CONCLUSIONS: ET(A) receptor activation stimulates,
      whereas ET(B) receptor activation inhibits, intestinal peristalsis. The ability
      of BQ-788 to facilitate peristalsis per se points to a physiologic role of ET(B)
      receptors in peristaltic motor regulation.

PMID- 10889158
TI  - Intestine-specific activity of the human guanylyl cyclase C promoter is regulated
      by Cdx2.
AB  - BACKGROUND & AIMS: The heat-stable enterotoxin receptor, guanylyl cyclase C,
      exhibits an intestine-specific pattern of expression. The aim of this study was
      to identify the transcriptional activator that mediates intestine-specific
      expression of guanylyl cyclase C. METHODS: Fragments of the promoter were assayed
      to isolate regions directing intestine-specific gene activation.
      Deoxyribonuclease I footprinting was used to identify a site of intestine
      specific protection. Electrophoretic mobility shift assays (EMSAs) and supershift
      analyses were used to characterize the protein that bound to the protected site.
      The protected site was mutated to analyze its role in promoter activity. RESULTS:
      Reporter gene assays revealed that intestine-specific expression of guanylyl
      cyclase C is directed by the proximal promoter. Deoxyribonuclease I footprinting
      identified a specific site in the proximal promoter that exhibited intestine
      specific protection. EMSAs and supershift analyses revealed that the
      transcription factor Cdx2 bound to an intestine-specific site of protection.
      Mutation of the Cdx2-protected site of the promoter eliminated binding of Cdx2
      and reduced reporter gene activity to the level of extraintestinal cells.
      CONCLUSIONS: These data show that Cdx2 and its consensus-binding site in the
      promoter are required for intestine-specific expression of the guanylyl cyclase C
      gene.

PMID- 10889159
TI  - H. pylori activates NF-kappaB through a signaling pathway involving IkappaB
      kinases, NF-kappaB-inducing kinase, TRAF2, and TRAF6 in gastric cancer cells.
AB  - BACKGROUND & AIMS: H. pylori infection on gastric epithelial cells has been shown
      to induce NF-kappaB activation, but the mechanism of intracellular signal
      conduction that leads to NF-kappaB activation is not clear. The aim of this study
      was to analyze the molecular mechanism responsible for H. pylori-mediated NF
      kappaB activation on gastric cancer cells. METHODS: NF-kappaB activation by H.
      pylori was tested by using luciferase reporter assay. IkappaBalpha degradation by
      H. pylori infection was assessed by immunoblotting. IKKalpha and IKKbeta
      activation was analyzed by kinase assay. In transfection experiments, effects of
      dominant negative IkappaBalpha, IKKalpha, IKKbeta, NF-kappaB-inducing kinase
      (NIK), TRAF2, and TRAF6 mutants were investigated. The effects of an IKKbeta
      specific inhibitor, aspirin, on NF-kappaB activation and IL-8 secretion were also
      analyzed. RESULTS: H. pylori promotes degradation of IkappaBalpha, a cytoplasmic
      inhibitor of NF-kappaB. In kinase assay, H. pylori induced IKKalpha and IKKbeta
      catalytic activity in gastric cancer cells. Transfection of kinase-deficient
      mutant of either IKK inhibited H. pylori-mediated NF-kappaB activation dose
      dependently. Aspirin inhibited both NF-kappaB activation and IL-8 secretion
      induced by H. pylori. NF-kappaB activation was also inhibited by transfection of
      kinase-deficient NIK or a dominant negative mutant of upstream adapter protein
      TRAF2 or TRAF6. CONCLUSIONS: H. pylori induces NF-kappaB activation through an
      intracellular signaling pathway that involves IKKalpha, IKKbeta, NIK, TRAF2, and
      TRAF6.

PMID- 10889160
TI  - Gastric mucosal alpha(4)beta(7)-integrin-positive CD4 T lymphocytes and immune
      protection against helicobacter infection in mice.
AB  - BACKGROUND & AIMS: The integrin alpha(4)beta(7) mediates homing of
      effector/memory lymphocytes to the intestine and the mucosa-associated lymphoid
      tissue. This study examined the ability of alpha(4)beta(7)(hi) CD4(+) T
      lymphocytes to home to the stomach and their role in immunization-mediated
      protection against Helicobacter felis infection. METHODS: Gastric lamina propria
      and circulating mononucleated cells of naive, infected, and immunized Swiss
      Webster mice were isolated, and alpha(4)beta(7)-integrin expression was
      quantified by flow cytometry on CD4(+) T lymphocytes. Anti-alpha(4)beta(7)
      integrin antibody was used to block alpha(4)beta(7) function in vivo. RESULTS: In
      naive mice, alpha(4)beta(7)(hi) CD4(+) T cells were enriched approximately 10
      fold in the gastric mucosa compared with peripheral blood (P<0.0001). Chronic H.
      felis infection did not alter these proportions, but oral immunization with H.
      felis sonicate plus cholera toxin (CT) or with CT alone markedly increased
      gastric alpha(4)beta(7)(hi) CD4(+) T cells compared with naive and infected
      controls (P = 0.0008 and P = 0.002 for H. felis sonicate and CT, respectively).
      Anti-alpha(4)beta(7)-integrin antibody blocked the protection induced by oral
      immunization with H. felis sonicate and CT. CONCLUSIONS: The integrin
      alpha(4)beta(7) participates in the homing of CD4(+) T lymphocytes to the stomach
      and in the protection of the gastric mucosa against H. felis infection.

PMID- 10889161
TI  - Activation of natural killer T cells by alpha-galactosylceramide in the presence
      of CD1d provides protection against colitis in mice.
AB  - BACKGROUND & AIMS: CD1d is a major histocompatibility complex class I-like
      molecule that presents glycolipid antigens to a subset of natural killer
      (NK)1.1(+) T cells. These NK T cells exhibit important immunoregulatory functions
      in several autoimmune disease models. METHODS: To investigate whether CD1d and NK
      T cells have a similar role in intestinal inflammation, the effects of the
      glycolipid, alpha-galactosylceramide (alpha-GalCer), on dextran sodium sulfate
      (DSS)-induced colitis were examined. Wild-type (WT), CD1d(-/-), and RAG(-/-) mice
      were examined for their response to either alpha-GalCer or the control analogue,
      alpha-mannosylceramide (alpha-ManCer). RESULTS: WT mice, but not CD1d(-/-) and
      RAG(-/-) mice, receiving alpha-GalCer had a significant improvement in DSS
      induced colitis based on body weight, bleeding, diarrhea, and survival when
      compared with those receiving alpha-ManCer. Elimination of NK T cells through
      antibody-mediated depletion resulted in a reduction of the effect of alpha
      GalCer. Furthermore, adoptive transfer of NK T cells preactivated by alpha
      GalCer, but not alpha-ManCer, resulted in diminished colitis. Using a fluorescent
      labeled analogue of alpha-GalCer, confocal microscopy localized alpha-GalCer to
      the colonic surface epithelium of WT but not CD1d(-/-) mice, indicating alpha
      GalCer binds CD1d in the intestinal epithelium and may be functionally active at
      this site. CONCLUSIONS: These results show an important functional role for NK T
      cells, activated by alpha-GalCer in a CD1d-restricted manner, in regulating
      intestinal inflammation.

PMID- 10889162
TI  - Interferon gamma induction during oral tolerance reduces T-cell migration to
      sites of inflammation.
AB  - BACKGROUND & AIMS: Previous data suggest that oral antigen induces interferon
      (IFN)-gamma production in intestinal T cells. However, oral tolerance is
      associated with decreased production of IFN-gamma by T cells after antigen
      sensitization. The aim of this study was to examine the role of IFN-gamma in oral
      tolerance. METHODS: Oral tolerance was examined in BALB/c mice after the adoptive
      transfer of T cells from chicken ovalbumin (OVA(323-339))-specific, DO11.10 x RAG
      1(-/-) T-cell receptor transgenic mice. RESULTS: OVA feeding induced systemic
      tolerance of delayed-type hypersensitivity (DTH) and antibody responses. OVA
      feeding up-regulated IFN-gamma production by transgenic T cells in Peyer's patch
      and mesenteric lymph node but not splenic tissues. Treatment of OVA-fed mice with
      neutralizing monoclonal antibody to IFN-gamma prevented tolerance of DTH
      responses. Analysis of transgenic T-cell numbers in DTH sites by
      immunohistochemical staining suggested that induction of IFN-gamma by oral
      antigen decreased accumulation of transgenic T cells in cutaneous sites of
      antigen injection. IFN-gamma-deficient or wild-type DO11.10 and BALB/c mice were
      used to show that IFN-gamma production by donor transgenic T cells was critical
      for oral tolerance. CONCLUSIONS: These data suggest that the induction of IFN
      gamma by oral antigen contributes to systemic tolerance by decreasing migration
      of T cells to peripheral sites of inflammation.

PMID- 10889163
TI  - Clostridium difficile toxin A causes early damage to mitochondria in cultured
      cells.
AB  - BACKGROUND & AIMS: The mechanism by which Clostridium difficile toxin A causes
      actin depolymerization and cell rounding involves toxin internalization and
      subsequent monoglucosylation of the Rho family of proteins. This study explored
      toxin internalization and effects on mitochondrial function before cell rounding.
      METHODS: Chinese hamster ovary (CHO) cells were exposed to toxin A, and
      mitochondrial localization was assayed by confocal microscopy. Mitochondrial
      function was measured by adenosine triphosphate (ATP) concentration,
      mitochondrial permeability, and leakage of cytochrome c. RESULTS: Confocal
      microscopy showed toxin A colocalization with the mitochondrial protein GRP 75 at
      5 minutes after toxin exposure. Between 5 and 15 minutes, toxin A caused an 80%
      diminution in cellular ATP levels; cell rounding and Rho glucosylation commenced
      between 15 and 30 minutes. Toxin A also resulted in reduction of mitochondrial
      membrane potential and a 2-3-fold increase in reactive oxygen radicals.
      Preincubation of CHO cells with the antioxidants butylated hydroxyanisole or
      butylated hydroxytoluene blocked the toxin A-induced increase in oxygen radicals
      and diminished cell rounding. Western blot analysis of toxin A-exposed isolated
      mitochondria showed a direct effect of toxin A on leakage of cytochrome c.
      CONCLUSIONS: The results show that extensive mitochondrial damage occurs within
      15 minutes in CHO cells exposed to toxin A. Diminished ATP concentrations and
      increased oxygen radicals are likely to contribute to cytotoxicity from this
      bacterial toxin.

PMID- 10889164
TI  - Effects of dietary folate on DNA strand breaks within mutation-prone exons of the
      p53 gene in rat colon.
AB  - BACKGROUND & AIMS: Diminished folate status has been observed to increase
      colorectal cancer risk. Folate plays an important role in DNA synthesis and
      repair. This study investigated the effects of dietary folate on DNA strand
      breaks in the p53 and Apc genes, and how these changes are related to steady
      state levels of the corresponding transcripts. METHODS: Three groups of rats were
      fed diets containing 0, 2 (basal requirement), or 8 mg folate/kg for 5 weeks. At
      each weekly time point, plasma and colonic mucosal folate concentrations were
      determined. Site-specific DNA strand breaks were assessed by semiquantitative
      PCR. Steady-state levels of messenger RNA were measured by semiquantitative RT
      PCR. RESULTS: Dietary folate deficiency produced progressive DNA strand breaks
      within exons 5-8 of the p53 gene in rat colon (P<0.02). Accumulation of strand
      breaks was not observed in other exons of the p53 gene, in the Apc and beta-actin
      genes, or at the genomic level. Folate supplementation at 4 times the basal
      requirement significantly increased p53 integrity compared with the basal and
      deficient diets (P<0.05). p53 integrity in exons 5-8 was significantly correlated
      with folate status (P<0.03). Dietary folate deprivation progressively decreased,
      whereas supplementation increased, steady-state levels of p53 transcript over 5
      weeks (P<0.05). No such changes were observed for the Apc gene. Steady-state
      levels of p53 transcript were significantly correlated with folate status and p53
      integrity in exons 5-8 (P<0.002). CONCLUSIONS: These data provide a plausible
      mechanism by which folate deficiency promotes, and folate supplementation
      suppresses, colorectal carcinogenesis.

PMID- 10889165
TI  - Progastrin expression predisposes mice to colon carcinomas and adenomas in
      response to a chemical carcinogen.
AB  - BACKGROUND & AIMS: Processing intermediates of preprogastrin (gly-gastrin and
      progastrin), termed nonamidated gastrins, are mitogenic for several cell types
      including colonic epithelial cells. However, presently it is not known if
      nonamidated gastrins play a role in colon carcinogenesis and if the effects are
      similar to those of amidated gastrins. METHODS: Colon carcinogenesis in response
      to azoxymethane (AOM) was examined in transgenic mice overexpressing either
      progastrin (hGAS) or amidated gastrin (INS-GAS), compared with that in wild-type
      (WT) mice. RESULTS: In AOM-treated groups, the total number of tumors per colon
      was significantly higher in hGAS (4.8+/-0.34) than INS-GAS (3.0+/-0.16) and WT
      (2.7+/-0.35) mice. Total numbers of adenocarcinomas and adenomas per animal colon
      were also significantly higher in hGAS than INS-GAS and WT mice. The size of the
      tumors was greater in hGAS mice, resulting in a significantly higher tumor burden
      per mouse in the hGAS mice than INS-GAS and WT mice. Although >90% of the tumors
      were located in the distal half of the colon in INS-GAS and WT mice, a
      significant number (42%) were present at the proximal end of the colon in hGAS
      mice. CONCLUSIONS: The results suggest that the risk for developing colon
      carcinomas and adenomas in response to AOM is significantly increased in mice
      expressing high levels of progastrin, but not amidated gastrins.

PMID- 10889166
TI  - Effects of extended lamivudine therapy in Asian patients with chronic hepatitis
      B. Asia Hepatitis Lamivudine Study Group.
AB  - BACKGROUND & AIMS: One-year lamivudine therapy significantly suppressed hepatitis
      B virus (HBV) replication, improved hepatic necroinflammatory activity, and
      prevented progression of fibrosis. However, the effects of prolonged therapy are
      unknown. METHODS: A total of 334 Asian patients with chronic hepatitis B from a
      previously reported 1-year study were randomized to receive either lamivudine
      (100 or 25 mg) or placebo for another year. The effects of treatment on serum HBV
      DNA suppression, alanine transaminase (ALT) normalization, and hepatitis B e
      antigen (HBeAg) seroconversion were measured. The presence of YMDD variant HBV
      and its effect were also determined. RESULTS: A significantly greater proportion
      of patients achieved sustained HBV-DNA suppression and ALT normalization with 100
      mg lamivudine daily for 2 years compared with lamivudine for 1 year followed by
      placebo for the second year (P<0.001). Daily lamivudine therapy for 2 years was
      safe and resulted in incremental HBeAg seroconversion from 17% at week 52 to 27%
      at week 104. HBeAg seroconversion during continued lamivudine therapy increased
      linearly with increasing pretherapy ALT levels (P< 0.001). Despite the emergence
      of YMDD mutant in 38% of the patients, they continued to clear serum HBeAg and
      maintain lower median serum HBV-DNA and ALT levels than baseline values. In
      contrast, ALT levels increased 8-12 weeks after switching from lamivudine to
      placebo, but returned to normal once lamivudine treatment was resumed.
      CONCLUSIONS: Treatment with lamivudine for 2 years is both well tolerated and
      efficacious in patients with chronic hepatitis B.

PMID- 10889167
TI  - Natural history of portal hypertensive gastropathy in patients with liver
      cirrhosis. The New Italian Endoscopic Club for the study and treatment of
      esophageal varices (NIEC).
AB  - BACKGROUND & AIMS: The clinical importance of portal hypertensive gastropathy
      (PHG) as a source of gastrointestinal bleeding in patients with cirrhosis is
      poorly defined. We investigated the natural history of this condition in a large
      series of patients. METHODS: All patients with cirrhosis seen at 7 hospitals
      during June and July 1992 were followed up with clinical and endoscopic
      examinations every 6 months for up to 3 years. Gastropathy was classified
      according to the classification of the New Italian Endoscopic Club. RESULTS: The
      prevalence of gastropathy was 80% and was correlated with the duration of
      disease, presence and size of esophagogastric varices, and a previous history of
      endoscopic variceal sclerotherapy. During 18+/-8 months of follow-up, gastropathy
      was stable in 29% of patients, deteriorated in 23%, improved in 23%, and
      fluctuated with time in 25%. The evolution of gastropathy with time was identical
      in patients with and without previous or current sclerotherapy. Acute bleeding
      from gastropathy occurred in 8 of 315 patients (2.5%). The bleeding-related
      mortality rate was 12.5%. Chronic bleeding occurred in 34 patients (10.8%).
      CONCLUSIONS: PHG is common in patients with cirrhosis, and its prevalence
      parallels the severity of portal hypertension. Gastropathy can progress from mild
      to severe and vice versa or even disappear completely. Bleeding from this lesion
      is relatively uncommon and rarely severe. Sclerotherapy of esophageal varices
      does not seem to influence the natural history of this condition.

PMID- 10889168
TI  - Abnormal hepatic sinusoidal bile acid transport in an Amish kindred is not linked
      to FIC1 and is improved by ursodiol.
AB  - BACKGROUND & AIMS: The mechanism for abnormal hepatic bile acid transport was
      investigated in an 18-month-old Amish boy who presented with pruritus, poor
      growth, and severe bleeding episodes. Serum bilirubin, gamma
      glutamyltranspeptidase, and cholesterol levels were normal, but prothrombin time
      and partial thromboplastin time were prolonged and bone alkaline phosphatase
      level was elevated. METHODS AND RESULTS: Cholic acid plus chenodeoxycholic acid
      levels measured by capillary gas-chromatography were 32 times higher than control
      in serum (34.7 vs. 1.1+/-0.4 microg/dL) but were not detected in liver and were
      reduced in gallbladder bile. Treatment with ursodiol, a more hydrophilic bile
      acid, improved pruritus, produced 37% weight gain, and after 2 years reduced
      serum primary bile acid concentrations about 85%, while accounting for 71% of
      serum and 24% of biliary bile acid conjugates. On ursodiol therapy, hepatic bile
      acid synthesis was enhanced 2-fold compared with controls, and microscopy
      revealed chronic hepatitis without cholestasis. Three younger sisters with
      elevated serum bile acids responded positively to ursodiol. Microsatellite
      markers for the FIC1 (gene for Byler's disease) region in these 4 children were
      inconsistent with linkage to FIC1. CONCLUSIONS: Conjugated cholic acid and
      chenodeoxycholic acid were synthesized in the liver and secreted into bile but
      could not reenter the liver from portal blood and accumulated in serum. In
      contrast, unconjugated ursodiol entered the liver and was conjugated and secreted
      into bile. Thus, the enterohepatic circulation of all conjugated bile acids was
      interrupted at the hepatic sinusoidal basolateral membrane. Unconjugated ursodiol
      bypassed the hepatic uptake block to enlarge the biliary and intestinal bile acid
      pools. A mutation in FIC1 recognized among the Amish and linkage of the disorder
      to FIC1 were excluded.

PMID- 10889170
TI  - Changes in protein kinase C isoforms in association with vascular hyporeactivity
      in cirrhotic rat aortas.
AB  - BACKGROUND & AIMS: Although protein kinase C (PKC) alterations may play a role in
      the abnormal reactivity of cirrhotic rat aortas, its isoforms and cellular
      distribution are unknown. We therefore studied the protein expression and
      cellular distribution of PKC isoforms and their activation in cirrhotic rat
      aortas. METHODS: Endothelium-denuded aortas from control and cirrhotic rats were
      examined. Immunoblots were performed with PKC isoform-specific antibodies. Aortic
      reactivity was determined for phorbol myristate acetate and phenylephrine after
      PKC down-regulation. RESULTS: PKC-alpha expression was reduced in both the
      cytosolic and membrane fractions in cirrhotic aortas. Trace amounts of PKC-beta
      were detected in cirrhotic aortas. PKC-delta was detected in the cytosolic
      fraction of control and cirrhotic aortas. PKC-zeta was detected in the membrane
      fraction in control aortas and in the cytosolic fraction in cirrhotic aortas.
      Phorbol myristate acetate and phenylephrine triggered translocation of PKC-alpha
      and PKC-delta isoforms from the cytosol to the membrane in control aortas; in
      cirrhotic aortas, only PKC-alpha was translocated. Aortic reactivities were
      reduced after PKC down-regulation. PKC-alpha and -delta activities were reduced
      in cirrhotic aortas. CONCLUSIONS: These results suggest that a change in PKC
      isoforms may be responsible in part for the abnormal reactivity and intracellular
      transduction through the PKC pathway in cirrhotic rat aortas.

PMID- 10889169
TI  - Role of aortic nitric oxide synthase 3 (eNOS) in the systemic vasodilation of
      portal hypertension.
AB  - BACKGROUND & AIMS: In portal hypertension, the mechanisms responsible for nitric
      oxide (NO) overproduction and vasodilation have not yet been clearly identified.
      One hypothesis is that NO synthase (NOS) 3 is overactivated because of shear
      stress in endothelial cells caused by hyperkinetic circulation. The aim of this
      study was to evaluate aortic NOS3 after a reduction of blood flow by long-time
      beta-adrenoceptor antagonist administration. METHODS: Propranolol or atenolol was
      administered by gavage in portal vein-stenosed and sham-operated rats. The
      vascular reactivity of thoracic aortic rings to phenylephrine, total aortic NOS
      activity, and aortic NOS3 messenger RNA and protein expressions were studied.
      RESULTS: After propranolol or atenolol administration, the aortic hyporesponse
      returned to normal in portal vein-stenosed rats. Total aortic NOS activity was
      higher in portal vein-stenosed aortas and significantly decreased after beta
      blocker administration. Aortic NOS3 expressions were more marked in portal vein
      stenosed aortas than in controls, but NOS3 expressions were reduced after
      propranolol administration. CONCLUSIONS: In portal hypertension, aortic NOS3
      activity and expressions are enhanced but return to normal after beta-blocker
      administration. These results suggest that in portal hypertension, increased
      shear stress, related to high blood flow, induces enhanced aortic NOS3.

PMID- 10889171
TI  - Cytokine regulation of chemokine (IL-8, MCP-1, and RANTES) gene expression in
      human pancreatic periacinar myofibroblasts.
AB  - BACKGROUND & AIMS: We have previously isolated and characterized human pancreatic
      periacinar myofibroblasts. In this study, to define the role of these cells in
      the pathogenesis of acute pancreatitis, we investigated chemokine expression in
      them. METHODS: Secretion of chemokines (interleukin [IL]-8, monocyte
      chemoattractant protein [MCP]-1, RANTES, and MIP [macrophage inflammatory
      protein]-1alpha) was evaluated by ELISA, Northern blotting, and nuclear run-on
      assays. The activation of NF-kappaB and NF-IL6 was assessed by an electrophoretic
      gel mobility shift assay. RESULTS: IL-8 and MCP-1 secretion was rapidly induced
      by both IL-1beta and tumor necrosis factor (TNF)-alpha. RANTES secretion was
      induced more slowly and was induced mainly by TNF-alpha. However, MIP-1alpha
      secretion was not induced by any stimuli. These responses were also observed at
      the messenger RNA level, and they were accompanied by an increase in
      transcriptional rate. The increase in transcriptional activation of chemokine
      genes correlated with the NF-kappaB and NF-IL6 activation. Furthermore, a
      blockade of NF-kappaB activation by PDTC and TPCK markedly reduced the IL-1beta-
      or TNF-alpha-induced chemokine gene expression. CONCLUSIONS: Chemokine secretion
      is differentially regulated in pancreatic periacinar myofibroblasts, suggesting a
      role for these cells in mediating the infiltration and accumulation of
      inflammatory cells in the pancreas.

PMID- 10889172
TI  - Water immersion stress induces heat shock protein 60 expression and protects
      against pancreatitis in rats.
AB  - BACKGROUND & AIMS: Heat shock proteins (Hsps), induced by cell stress, are known
      to protect against cellular injury. Recent studies have indicated that Hsp60
      expression, induced by exposure to water immersion stress, protects against
      pancreatitis induced by administration of supramaximal doses of cerulein in rats.
      However, the mechanisms responsible for this protection are not known. METHODS:
      Rats were water-immersed for 3-12 hours. Pancreatitis was induced by cerulein
      administration. RESULTS: The results confirm that prior induction of Hsp60
      expression by water-immersion stress significantly ameliorates the severity of
      cerulein-induced pancreatitis as judged by the markedly reduced degree of
      hyperamylasemia, pancreatic edema, and acinar cell necrosis. Water immersion also
      prevents the subcellular redistribution of cathepsin B from a lysosome-enriched
      fraction to a heavier, zymogen granule-enriched fraction that is known to occur
      in this model of pancreatitis. Intra-acinar cell activation of trypsinogen that
      occurs shortly after exposure to a supramaximally stimulating dose of cerulein
      both in vivo and in vitro is prevented by prior water-immersion stress and Hsp60
      expression. The protection against pancreatitis that follows water-immersion
      stress is not caused by alterations of cholecystokinin receptors, because water
      immersion does not alter the typical biphasic amylase secretory response to
      stimulation with cerulein. CONCLUSIONS: Water-immersion stress induces Hsp60
      expression, ameliorates cerulein-induced pancreatitis, and prevents intra-acinar
      cell activation of trypsinogen. We suggest that Hsp60 protects against cerulein
      induced pancreatitis by preventing trypsinogen activation within acinar cells.

PMID- 10889173
TI  - Acute pancreatitis attributed to the use of interferon alfa-2b.
AB  - Two patients experienced episodes of acute pancreatitis shortly after starting
      treatment with interferon alfa-2b (IFN-alpha) for a chronic hepatitis C
      infection. The first patient was a 40-year-old man who developed acute
      pancreatitis after 15 weeks of treatment with 3 MU IFN-alpha subcutaneously (SC)
      3 times weekly and 1200 mg ribavirin. After disappearance of symptoms and
      normalization of laboratory values, oral intake of solid foods and IFN-alpha
      therapy were restarted. Within hours, a relapse of acute pancreatitis occurred. A
      rechallenge with IFN-alpha 4 days later was followed by a prompt increase in
      serum lipase level, and IFN-alpha therapy was discontinued. The second patient
      was a 38-year-old man who developed acute pancreatitis 2 hours after SC
      administration of 5 MU IFN-alpha. Ultrasound endoscopy showed sludge in the
      gallbladder. The patient was rechallenged 5 weeks later with 3 MU IFN-alpha SC.
      Although serum amylase and lipase levels increased after readministration of IFN
      alpha, treatment was continued. The patient was readmitted 2 weeks later with
      severe abdominal pain, and IFN-alpha administration was discontinued. Considering
      the temporal relationship between the start of IFN-alpha treatment and
      development of acute pancreatitis, the absence of other clear etiologic factors
      for acute pancreatitis, disappearance of symptoms after discontinuation of IFN
      alpha, and positive reactions to rechallenge, IFN-alpha is the most probable
      cause for development of acute pancreatitis in these patients.

PMID- 10889174
TI  - Current concepts of celiac disease pathogenesis.
AB  - Our knowledge of celiac disease pathogenesis has recently made rapid progress.
      The disorder is now considered the result of a complex interplay of intrinsic
      (genetic) and variable extrinsic (environmental) factors that explain the wide
      spectrum of clinical manifestations ranging from asymptomatic to severe
      malabsorption. Gluten peptides are efficiently presented by celiac disease
      specific HLA-DQ2- and HLA-DQ8-positive antigen-presenting cells, and thus drive
      the immune response, predominantly in the connective tissue of the lamina
      propria. Tissue transglutaminase, which has been identified as the highly
      specific endomysial autoantigen, is released from cells during inflammation. It
      may potentiate antigen presentation by HLA-DQ2 and HLA-DQ8 by deamidating or
      cross-linking gluten peptides. The result is lamina propria T-cell activation and
      mucosal transformation by activated intestinal fibroblasts. In the future,
      manipulation of the gut-associated lymphoid tissue may allow reduced sensitivity
      or even generate oral tolerance to gluten. Long-standing untreated celiac
      disease, even if clinically silent, predisposes for other autoimmune diseases.
      Therefore, population screening for immunoglobulin A antibodies to tissue
      transglutaminase seems justified.

PMID- 10889175
TI  - Refractory celiac disease.
AB  - Celiac disease is a gluten-sensitive enteropathy, characterized by villous
      atrophy, which is reversed by gluten withdrawal. A minority of patients with
      celiac-like enteropathy are resistant to gluten-free diet, so-called refractory
      sprue, or unclassified sprue. Refractory sprue is a diagnosis of exclusion; all
      other causes of a celiac-like enteropathy must be eliminated before a diagnosis
      of refractory sprue can be made. Recent evidence suggests that refractory sprue
      comprises a heterogenous group of patients with diverse underlying causes. A
      small proportion of these patients seem to have an adult form of autoimmune
      enteropathy, characterized by the presence of antienterocyte antibodies. However,
      a larger group of patients with refractory sprue now seem to have a cryptic
      intestinal T-cell lymphoma, characterized by the presence of phenotypically
      abnormal, monoclonal intraepithelial lymphocytes, despite benign cytology.
      Current therapeutic options include nutritional support and immunosuppressive
      therapy, but response is variable. The prognosis of refractory sprue may be poor;
      patients may die of severe malabsorption, or through synchronous or metachronous
      development of an enteropathy-associated T-cell lymphoma. Based on this recent
      evidence, patients with refractory sprue should be screened for antienterocyte
      antibodies and have T-cell receptor and monoclonal antibody studies performed;
      this could facilitate identification of cases of adult-onset autoimmune
      enteropathy and those of cryptic T-cell lymphoma. Moreover, early recognition of
      the malignant nature of the intestinal infiltrate in some cases of refractory
      sprue could permit the development of novel chemotherapeutic regimens for this
      condition.

PMID- 10889176
TI  - A year in the life of the gastric mucosa.

PMID- 10889177
TI  - Commensal bacteria as targets in Crohn's disease.

PMID- 10889178
TI  - Neuropeptides and colonic motility: it's all in the little brain.

PMID- 10889179
TI  - New insights into oral tolerance.

PMID- 10889180
TI  - Lamivudine therapy for chronic hepatitis B: is longer duration of treatment
      better?

PMID- 10889181
TI  - Prevention of colorectal cancer: tumor progression, chemoprevention, and COX-2
      inhibition.

PMID- 10889182
TI  - A CF modifier means meconium in mouse and man.

PMID- 10889183
TI  - Gene therapy for food allergy.

PMID- 10889185
TI  - Pediatric gastrointestinal disease: pathophysiology, diagnosis and management

PMID- 10889184
TI  - 5-HT(3) antagonist therapy of bulimia nervosa: a peripherally active agent for a
      central nervous system eating disorder?

PMID- 10889186
TI  - Molecular cloning and characterization of another leukotriene B4 receptor.
AB  - Leukotriene B(4) is a potent lipid mediator known to be implicated mainly in
      inflammatory actions. Previous pharmacological studies indicated the existence of
      only one class of G protein-coupled receptor for leukotriene B(4), for which a
      candidate gene, namely BLT, had been identified. Here we report the isolation of
      another gene encoding a functional G protein-coupled receptor for leukotriene
      B(4), named JULF2. JULF2 is a novel G protein-coupled receptor of 358 amino acids
      that shares 36.6% amino acid identity with human BLT. According to genomic
      information, the JULF2 gene is located on the chromosome 14, about 4 kilobases
      upstream of the BLT gene. During screening of endogenous ligands for JULF2, we
      found that leukotriene B(4) induced inhibition of forskolin-stimulated cAMP
      accumulation in Chinese hamster ovary cells, stably expressing JULF2.
      Additionally, Chinese hamster ovary cells expressing exogenous JULF2 showed
      chemotactic responses with leukotriene B(4) in a pertussis toxin-sensitive
      manner. A large amount of JULF2 mRNA was detected in the human spleen and the
      peripheral blood leukocytes. Furthermore, JULF2 mRNA was expressed in mononuclear
      lymphocytes, in which BLT mRNA was barely detected. The discovery of this second
      leukotriene B(4) receptor will eventually lead to a better understanding of the
      classification of leukotriene B(4) receptors and reconsideration of the
      pathophysiological role of leukotriene B(4).

PMID- 10889187
TI  - Human plasmin enzymatic activity is inhibited by chemically modified dextrans.
AB  - Some synthetic dextran derivatives that mimic the action of heparin/heparan
      sulfate were shown to promote in vivo tissue repair when added alone to wounds.
      These biofunctional mimetics were therefore designated as "regenerating agents"
      in regard to their in vivo properties. In vitro, these biopolymers were able to
      protect various heparin-binding growth factors against proteolytic degradation as
      well as to inhibit the enzymatic activity of neutrophil elastase. In the present
      work, different dextran derivatives were tested for their capacity to inhibit the
      enzymatic activity of human plasmin. We show that dextran containing
      carboxymethyl, sulfate as well as benzylamide groups (RG1192 compound), was the
      most efficient inhibitor of plasmin amidolytic activity. The inhibition of
      plasmin by RG1192 can be classified as tight binding hyperbolic noncompetitive.
      One molecule of RG1192 bound 20 molecules of plasmin with a K(i) of 2.8 x 10(-8)
      m. Analysis with an optical biosensor confirmed the high affinity of RG1192 for
      plasmin and revealed that this polymer equally binds plasminogen with a similar
      affinity (K(d) = 3 x 10(-8) m). Competitive experiments carried out with 6
      aminohexanoic acid and kringle proteolytic fragments identified the lysine
      binding site domains of plasmin as the RG1192 binding sites. In addition, RG1192
      blocked the generation of plasmin from Glu-plasminogen and inhibited the plasmin
      mediated proteolysis of fibronectin and laminin. Data from the present in vitro
      investigation thus indicated that specific dextran derivatives can contribute to
      the regulation of plasmin activity by impeding the plasmin generation, as a
      result of their binding to plasminogen and also by directly affecting the
      catalytic activity of the enzyme.

PMID- 10889188
TI  - Epidermal growth factor-mediated caveolin recruitment to early endosomes and MAPK
      activation. Role of cholesterol and actin cytoskeleton.
AB  - The endocytic compartment of eukaryotic cells is a complex intracellular
      structure involved in sorting, processing, and degradation of a great variety of
      internalized molecules. Recently, the uptake through caveolae has emerged as an
      alternative internalization pathway, which seems to be directly related with some
      signal transduction pathways. However, the mechanisms, molecules, and structures
      regulating the transport of caveolin from the cell surface into the endocytic
      compartment are largely unknown. In this study, normal quiescent fibroblasts
      (normal rat kidney (NRK)) were used to demonstrate that epidermal growth factor
      causes partial redistribution of caveolin from the cell surface into a
      cellubrevin early endocytic compartment. Treatment of NRK cells with cytochalasin
      D or latrunculin A inhibits this pathway and the concomitant activation of Mek
      and mitotic-activated protein (MAP) kinase; however, if cells were pre-treated
      with filipin, cytochalasin D does not inhibit the phosphorylation of MAP kinase
      induced by epidermal growth factor. From these results we conclude that in NRK
      cells the intact actin cytoskeleton is necessary for the EGF-mediated transport
      of caveolin from the cell surface into the early endocytic compartment and the
      activation of MAP kinase pathway.

PMID- 10889189
TI  - RalGEF2, a pleckstrin homology domain containing guanine nucleotide exchange
      factor for Ral.
AB  - Ral is a ubiquitously expressed Ras-like small GTPase. Several guanine nucleotide
      exchange factors for Ral have been identified, including members of the RalGDS
      family, which exhibit a Ras binding domain and are regulated by binding to
      RasGTP. Here we describe a novel type of RalGEF, RalGEF2. This guanine nucleotide
      exchange factor has a characteristic Cdc25-like catalytic domain at the N
      terminus and a pleckstrin homology (PH) domain at the C terminus. RalGEF2 is able
      to activate Ral both in vivo and in vitro. Deletion of the PH domain results in
      an increased cytoplasmic localization of the protein and a corresponding
      reduction in activity in vivo, suggesting that the PH domain functions as a
      membrane anchor necessary for optimal activity in vivo.

PMID- 10889190
TI  - Gene activation by Varicella-zoster virus IE4 protein requires its dimerization
      and involves both the arginine-rich sequence, the central part, and the carboxyl
      terminal cysteine-rich region.
AB  - Varicella-zoster virus (VZV) open reading frame 4-encoded protein (IE4) possesses
      transactivating properties for VZV genes as well as for those of heterologous
      viruses. Since most transcription factors act as dimers, IE4 dimerization was
      studied using the mammalian two-hybrid system. Introduction of mutations in the
      IE4 open reading frame demonstrated that both the central region and the carboxyl
      terminal cysteine-rich domain were important for efficient dimerization. Within
      the carboxyl-terminal domain, substitution of amino acids encompassing residues
      443-447 totally abolished dimerization. Gene activation by IE4 was studied by
      transient transfection with an IE4 expression plasmid and a reporter gene under
      the control of either the human immunodeficiency virus, type 1, long terminal
      repeat or the VZV thymidine kinase promoter. Regions of IE4 important for
      dimerization were also shown to be crucial for transactivation. In addition, the
      arginine-rich domains Rb and Rc of the amino-terminal region were also
      demonstrated to be important for transactivation, whereas the Ra domain as well
      as an acidic and bZIP-containing regions were shown to be dispensable for gene
      transactivation. A nucleocytoplasmic shuttling of IE4 has also been
      characterized, involving a nuclear localization signal identified within the Rb
      domain and a nuclear export mechanism partially depending on Crm-1.

PMID- 10889191
TI  - The propeptide domain of membrane type 1-matrix metalloproteinase acts as an
      intramolecular chaperone when expressed in trans with the mature sequence in COS
      1 cells.
AB  - It has been assumed that cleavage of the N-terminal propeptide domain of membrane
      type-1 matrix metalloproteinase (MT1-MMP) is required for enzyme function. We
      recently demonstrated that the propeptide domain of MT1-MMP is not cleaved and
      actually is required for function of the membrane-bound enzyme in transfected COS
      1 cells (Cao, J., Drews, M., Lee, H. M., Conner, C., Bahou, W. F., and Zucker, S.
      (1998) J. Biol. Chem. 273, 34745-34752). In this report, we have inserted the
      cDNA encoding the signal and propeptide sequences of MT1-MMP (MT(1-109)) and the
      cDNA encoding propeptide-deleted mature MT1-MMP (MT delta pro) in expression
      vectors that were then transfected into matrix metalloproteinase-deficient COS-1
      cells. Co-expression of both the mature sequence and the prosequence of MT1-MMP
      as independent polypeptides (in trans) in COS-1 cells resulted in reconstitution
      of MT1-MMP function in terms of facilitating (125)I-labeled tissue inhibitor of
      metalloproteinase 2 binding to transfected cells and subsequent activation of
      progelatinase A. Transfection of cells with either cDNA alone resulted in non
      functional cells. These results are consistent with the propeptide sequence of
      MT1-MMP functioning as an intramolecular chaperone involved in protein folding
      and trafficking to the cell surface.

PMID- 10889192
TI  - Binding of the NG2 proteoglycan to kringle domains modulates the functional
      properties of angiostatin and plasmin(ogen).
AB  - Interactions of the developmentally regulated chondroitin sulfate proteoglycan
      NG2 with human plasminogen and kringle domain-containing plasminogen fragments
      have been analyzed by solid-phase immunoassays and by surface plasmon resonance.
      In immunoassays, the core protein of NG2 binds specifically and saturably to
      plasminogen, which consists of five kringle domains and a serine protease domain,
      and to angiostatin, which contains plasminogen kringle domains 1-3. Apparent
      dissociation constants for these interactions range from 12 to 75 nm. Additional
      evidence for NG2 interaction with kringle domains comes from its binding to
      plasminogen kringle domain 4 and to miniplasminogen (kringle domain 5 plus the
      protease domain) with apparent dissociation constants in the 18-71 nm range.
      Inhibition of plasminogen and angiostatin binding to NG2 by 6-aminohexanoic acid
      suggests that lysine binding sites are involved in kringle interaction with NG2.
      The interaction of NG2 with plasminogen and angiostatin has very interesting
      functional consequences. 1) Soluble NG2 significantly enhances the activation of
      plasminogen by urokinase type plasminogen activator. 2) The antagonistic effect
      of angiostatin on endothelial cell proliferation is inhibited by soluble NG2.
      Both of these effects of NG2 should make the proteoglycan a positive regulator of
      the cell migration and proliferation required for angiogenesis.

PMID- 10889193
TI  - Thyrotropin-releasing hormone and epidermal growth factor regulate iron
      regulatory protein binding in pituitary cells via protein kinase C-dependent and 
      independent signaling pathways.
AB  - Intracellular iron homeostasis is regulated, in part, by interactions between
      iron-regulatory proteins (IRP1 and IRP2) and iron-responsive elements (IREs) in
      ferritin and transferrin receptor mRNAs. In addition to iron, cellular oxidative
      stress induced by H(2)O(2), nitric oxide, and hypoxia, and hormonal activation by
      thyroid hormone and erythropoeitin have each been shown to regulate IRP binding
      to IREs. Hormonal signals, in particular mediated through protein kinase C (PKC),
      play a central role in the modulation of IRP/IRE interactions since phorbol
      esters were shown to activate IRP binding (Eisenstein, R. S., Tuazon, P. T.,
      Schalinske, K. L., Anderson, S. A., and Traugh, J. A. (1993) J. Biol. Chem. 268,
      27363-27370). In pituitary thyrotrophs (TtT97), we found that thyrotropin
      releasing hormone (TRH) and epidermal growth factor (EGF) increased IRP binding
      to a ferritin IRE, dependent on PKC and mitogen-activated protein kinase (MAPK)
      activity. In contrast, TRH and EGF decreased IRP binding in pituitary lactotrophs
      (GH3), despite activation of PKC and MAPK. IRP1 and IRP2 levels remained constant
      and IRP2 binding was predominant throughout. TRH and EGF markedly decreased IRP
      binding in MAPK kinase inhibitor-treated GH3 cells, whereas, they increased IRP
      binding in phosphatase inhibitor-treated GH3 cells. IRE-dependent CAT reporter
      translational expression closely reflected IRP binding to the ferritin IRE in
      both GH3 and TtT97 cells. Interestingly, ferritin protein levels were regulated
      similarly by TRH in both cell lines. These data link two different cell receptor
      systems to common signaling pathways that regulate IRP binding and ferritin
      expression. Remarkably, for TRH and EGF, these effects may be PKC-dependent or 
      independent determined by the cell type.

PMID- 10889194
TI  - Understanding glucose transport by the bacterial phosphoenolpyruvate:glycose
      phosphotransferase system on the basis of kinetic measurements in vitro.
AB  - The kinetic parameters in vitro of the components of the
      phosphoenolpyruvate:glycose phosphotransferase system (PTS) in enteric bacteria
      were collected. To address the issue of whether the behavior in vivo of the PTS
      can be understood in terms of these enzyme kinetics, a detailed kinetic model was
      constructed. Each overall phosphotransfer reaction was separated into two
      elementary reactions, the first entailing association of the phosphoryl donor and
      acceptor into a complex and the second entailing dissociation of the complex into
      dephosphorylated donor and phosphorylated acceptor. Literature data on the K(m)
      values and association constants of PTS proteins for their substrates, as well as
      equilibrium and rate constants for the overall phosphotransfer reactions, were
      related to the rate constants of the elementary steps in a set of equations; the
      rate constants could be calculated by solving these equations simultaneously. No
      kinetic parameters were fitted. As calculated by the model, the kinetic parameter
      values in vitro could describe experimental results in vivo when varying each of
      the PTS protein concentrations individually while keeping the other protein
      concentrations constant. Using the same kinetic constants, but adjusting the
      protein concentrations in the model to those present in cell-free extracts, the
      model could reproduce experiments in vitro analyzing the dependence of the flux
      on the total PTS protein concentration. For modeling conditions in vivo it was
      crucial that the PTS protein concentrations be implemented at their high in vivo
      values. The model suggests a new interpretation of results hitherto not
      understood; in vivo, the major fraction of the PTS proteins may exist as
      complexes with other PTS proteins or boundary metabolites, whereas in vitro, the
      fraction of complexed proteins is much smaller.

PMID- 10889195
TI  - Localization of the N-terminal domain of the low density lipoprotein receptor.
AB  - The low density lipoprotein (LDL) receptor is a transmembrane glycoprotein
      performing "receptor-mediated endocytosis" of cholesterol-rich lipoproteins. At
      the N terminus, the LDL receptor has modular cysteine-rich repeats in both the
      ligand binding domain and the epidermal growth factor (EGF) precursor homology
      domain. Each repeat contains six disulfide-bonded cysteine residues, and this
      structural motif has also been found in many other proteins. The bovine LDL
      receptor has been purified and reconstituted into egg yolk phosphatidylcholine
      vesicle bilayers. Using gel electrophoresis and cryoelectron microscopy (cryoEM),
      the ability of the reconstituted LDL receptor to bind its ligand LDL has been
      demonstrated. After reduction of the disulfide-bonds in the N-terminal domain of
      the receptor, the reduced LDL receptor was visualized using cryoEM; reduced LDL
      receptors showed images with a diffuse density region at the distal end of the
      extracellular domain. Gold labeling of the reduced cysteine residues was achieved
      with monomaleimido-Nanogold, and the bound Nanogold was visualized in cryoEM
      images of the reduced, gold-labeled receptor. Multiple gold particles were
      observed in the diffuse density region at the distal end of the receptor. Thus,
      the location of the ligand binding domain of the LDL receptor has been
      determined, and a model is suggested for the arrangement of the seven cysteine
      rich repeats of the ligand binding domain and two EGF-like cysteine-rich repeats
      of the EGF precursor homology domain.

PMID- 10889196
TI  - Vesicle-reconstituted low density lipoprotein receptor. Visualization by
      cryoelectron microscopy.
AB  - The low density lipoprotein (LDL) receptor is a key protein for maintaining
      cellular cholesterol homeostasis by binding cholesterol-rich lipoproteins through
      their apoB and apoE apoproteins. The LDL receptor is a transmembrane glycoprotein
      of M(r) approximately 115 kDa; based on its primary sequence, five distinct
      structural domains have been identified (Yamamoto, T., Davis, C. G., Brown, M.
      S., Schneider, W. J., Casey, M. L., Goldstein, J. L., and Russell, D. W. (1984)
      Cell 39, 27-38). As a first step toward providing a structural description of the
      intact LDL receptor, the receptor has been purified from bovine adrenal cortices,
      reconstituted into unilamellar egg yolk phosphatidylcholine vesicles, and imaged
      using cryoelectron microscopy (cryoEM). CryoEM has the advantage of providing
      images of the reconstituted LDL receptor in its frozen, fully hydrated state. LDL
      receptor molecules were visualized as elongated, stick-like projections from the
      vesicle surface with maximum dimensions approximately 120-A length by
      approximately 45-A width. In some of the images, a short arm (or arms) was
      visible at the distal end of the stick-like projections. The LDL receptor was
      labeled via accessible free cysteine residues, probably including that
      corresponding to Cys-431 of the known full-length sequence of the human LDL
      receptor. The accessible cysteine was demonstrated using a maleimide
      biotin.streptavidin conjugate and confirmed by labeling with monomaleimido
      Nanogold. Images obtained by cryoEM showed that the extracellular stick-like
      domain of the reconstituted LDL receptor was labeled by Nanogold. This combined
      cryoEM-Nanogold labeling study has provided the first low resolution structural
      images of the reconstituted, full-length bovine LDL receptor.

PMID- 10889197
TI  - Early endosomal localization of hrs requires a sequence within the proline- and
      glutamine-rich region but not the FYVE finger.
AB  - Hrs is an early endosomal protein that is tyrosine-phosphorylated in cells
      stimulated with growth factors. Hrs is thought to play a regulatory role in
      endocytosis of growth factor-receptor complexes through early endosomes. Early
      endosomal localization of Hrs seems to be essential for Hrs to exert its function
      in the endocytosis. Hrs has a FYVE finger domain that binds specifically to
      phosphatidylinositol 3-phosphate in vitro. The FYVE finger is a likely domain
      that mediates membrane association of endosomal proteins. In this study, we
      examined whether the FYVE finger participates in early endosomal targeting of
      Hrs. Hrs with a zinc binding-defective FYVE finger was still localized to early
      endosomes. In addition, the N-terminal FYVE finger-containing fragment of Hrs
      showed a cytosolic distribution in mammalian cells. These results indicate that
      the FYVE finger is not required for the localization of Hrs to early endosomes.
      Furthermore, by analyzing a series of deletion mutants of Hrs, we identified a
      sequence of about 100 amino acids within the C-terminal proline- and glutamine
      rich region as a domain essential for the targeting of Hrs to early endosomes.

PMID- 10889198
TI  - Cell swelling-induced translocation of rat liver Na(+)/taurocholate cotransport
      polypeptide is mediated via the phosphoinositide 3-kinase signaling pathway.
AB  - Cell swelling stimulates phosphoinositide 3-kinase (PI3K) and mitogen-activated
      protein kinase (MAPK) in hepatocytes, and the PI3K signaling pathway is involved
      in cAMP-mediated translocation of sinusoidal Na(+)/taurocholate (TC)
      cotransporter (Ntcp) to the plasma membrane. We determined whether cell swelling
      also stimulates TC uptake and Ntcp translocation via the PI3K and/or MAPK
      signaling pathway. All studies were conducted in isolated rat hepatocytes.
      Hepatocyte swelling induced by hypotonic media resulted in: 1) time- and medium
      osmolarity-dependent increases in TC uptake, 2) an increase in the V(max) of
      Na(+)/TC cotransport, and 3) wortmannin-sensitive increases in TC uptake and
      plasma membrane Ntcp mass. Hepatocyte swelling also induced wortmannin-sensitive
      activation of PI3K, protein kinase B, and p70(S6K). Rapamycin, an inhibitor of
      p70(S6K), inhibited cell swelling-induced activation of p70(S6K) but failed to
      inhibit cell swelling-induced stimulation of TC uptake. Because PD98095, an
      inhibitor of MAPK, did not inhibit cell swelling-induced increases in TC uptake,
      it is unlikely that the effect of cell swelling on TC uptake is mediated via the
      MAPK signaling pathway. Taken together, these results indicate that 1) cell
      swelling stimulates TC uptake by translocating Ntcp to the plasma membrane, 2)
      this effect is mediated via the PI3K, but not MAPK, signaling pathway, and 3)
      protein kinase B, but not p70(S6K), is a likely downstream effector of PI3K.

PMID- 10889199
TI  - Retrovirally mediated transfer of a G protein-coupled receptor kinase (GRK)
      dominant-negative mutant enhances endogenous calcitonin receptor signaling in
      Chinese hamster ovary cells. GRK inhibition enhances expression of receptors and
      receptor mRNA.
AB  - G protein-coupled receptor kinases (GRKs) initiate pathways leading to agonist
      dependent phosphorylation and desensitization of G protein-coupled receptors.
      However, the role of GRKs in modulation of signaling properties of native
      receptors has not been clearly defined. Here we addressed this question by
      generating Chinese hamster ovary (CHO) cells stably expressing a dominant
      negative mutant of GRK2 (DN-GRK2), K220R, using retrovirally mediated gene
      transfer, and we assessed function of the endogenously expressed calcitonin (CT)
      receptors. We found that CT-mediated responses were prominently enhanced in CHO
      cells expressing DN-GRK2 compared with mock-infected control CHO cells with
      approximately 3-fold increases in CT-promoted cAMP production in whole cells and
      adenylyl cyclase activity in membrane fractions. CT-promoted phosphoinositide
      hydrolysis was also enhanced in DN-GRK2 cells. The number of CT receptors was
      increased approximately 3-fold in DN-GRK2 cells, as assessed by (125)I-salmon CT
      specific binding, and this was associated with increased CT receptor mRNA levels.
      These results indicate that DN-GRK2 has multiple consequences for CT receptor
      signaling, but a primary effect is an increase in CT receptor mRNA and receptor
      number and, in turn, enhanced CT receptor signaling. As such, our findings
      provide a mechanistic basis for previous observations regarding agonist-promoted
      down-regulation of CT receptors and for resistance and escape from response to CT
      in vitro and in vivo. Moreover, the data suggest that blunting of receptor
      desensitization by DN-GRK2 blocks a GRK-mediated tonic inhibition of CT receptor
      expression and response. We speculate that GRKs play a similar role for other G
      protein-coupled receptors as well.

PMID- 10889200
TI  - Internalization and sequestration of the human prostacyclin receptor.
AB  - Prostacyclin (PGI(2)), the major product of cyclooxygenase in macrovascular
      endothelium, mediates its biological effects through its cell surface G protein
      coupled receptor, the IP. PKC-mediated phosphorylation of human (h) IP is a
      critical determinant of agonist-induced desensitization (Smyth, E. M., Hong Li,
      W., and FitzGerald, G. A. (1998) J. Biol. Chem. 273, 23258-23266). The regulatory
      events that follow desensitization are unclear. We have examined agonist-induced
      sequestration of hIP. Human IP, tagged at the N terminus with hemagglutinin (HA)
      and fused at the C terminus to the green fluorescent protein (GFP), was coupled
      to increased cAMP (EC(50) = 0.39 +/- 0.09 nm) and inositol phosphate (EC(50) =
      86. 6 +/- 18.3 nm) generation when overexpressed in HEK 293 cells. Iloprost
      induced sequestration of HAhIP-GFP, followed in real time by confocal microscopy,
      was partially colocalized to clathrin-coated vesicles. Iloprost induced a time-
      and concentration-dependent loss of cell surface HA, indicating receptor
      internalization, which was prevented by inhibitors of clathrin-mediated
      trafficking and partially reduced by cotransfection of cells with a dynamin
      dominant negative mutant. Sequestration (EC(50) = 27.6 +/- 5.7 nm) was evident at
      those concentrations of iloprost that induce PKC-dependent desensitization.
      Neither the PKC inhibitor GF109203X nor mutation of Ser-328, the site for PKC
      phosphorylation, altered receptor sequestration indicating that, unlike
      desensitization, internalization is PKC-independent. Deletion of the C terminus
      prevented iloprost-induced internalization, demonstrating the critical nature of
      this region for sequestration. Internalization was unaltered by cotransfection of
      cells with G protein-coupled receptor kinases (GRK)-2, -3, -5, -6, arrestin-2, or
      an arrestin-2 dominant negative mutant, indicating that GRKs and arrestins do not
      play a role in hIP trafficking. The hIP is sequestered in response to agonist
      activation via a PKC-independent pathway that is distinct from desensitization.
      Trafficking is dependent on determinants located in the C terminus, is
      GRK/arrestin-independent, and proceeds in part via a dynamin-dependent clathrin
      coated vesicular endocytotic pathway although other dynamin-independent pathways
      may also be involved.

PMID- 10889201
TI  - Three classes of ubiquinone analogs regulate the mitochondrial permeability
      transition pore through a common site.
AB  - To identify the structural features required for regulation of the mitochondrial
      permeability transition pore (PTP) by ubiquinone analogs (Fontaine, E., Ichas,
      F., and Bernardi, P. (1998) J. Biol. Chem. 40, 25734-25740), we have carried out
      an analysis with quinone structural variants. We show that three functional
      classes can be defined: (i) PTP inhibitors (ubiquinone 0, decylubiquinone,
      ubiquinone 10, 2,3-dimethyl-6-decyl-1,4-benzoquinone, and 2,3,5-trimethyl-6
      geranyl-1,4-benzoquinone); (ii) PTP inducers (2,3-dimethoxy-5-methyl-6-(10
      hydroxydecyl)-1,4-benzoquinone and 2,5-dihydroxy-6-undecyl-1,4-benzoquinone); and
      (iii) PTP-inactive quinones that counteract the effects of both inhibitors and
      inducers (ubiquinone 5 and 2,3,5-trimethyl-6-(3-hydroxyisoamyl)-1,4-benzoquinone)
      . The structure-function correlation indicates that minor modifications in the
      isoprenoid side chain can turn an inhibitor into an activator, and that the
      methoxy groups are not essential for the effects of quinones on the PTP. Since
      the ubiquinone analogs used in this study have a similar midpoint potential and
      decrease mitochondrial production of reactive oxygen species to the same extent,
      these results support the hypothesis that quinones modulate the PTP through a
      common binding site rather than through oxidation-reduction reactions. Occupancy
      of this site can modulate the PTP open-closed transitions, possibly through
      secondary changes of the PTP Ca(2+) binding affinity.

PMID- 10889202
TI  - Characterization of peroxisomal Pex5p from rat liver. Pex5p in the Pex5p-Pex14p
      membrane complex is a transmembrane protein.
AB  - Pex5p is the receptor for the vast majority of peroxisomal matrix proteins. Here,
      we show that about 15% of rat liver Pex5p is found in the peroxisomal fraction
      representing 0.06% of total peroxisomal protein. This population of Pex5p
      displays all the characteristics of an intrinsic membrane protein. Protease
      protection assays indicate that this pool of Pex5p has domains exposed on both
      sides of the peroxisomal membrane. The strong interaction of Pex5p with the
      membrane of the organelle is not affected by mild protease treatment of intact
      organelles, conditions that result in the partial degradation of Pex13p.
      Cytosolic Pex5p is a monomeric protein. In contrast, virtually all peroxisomal
      Pex5p was found to be part of a stable 250-kDa protein assembly. This complex was
      isolated and shown to comprise just two subunits, Pex5p and Pex14p.

PMID- 10889203
TI  - Unconventional myosin VIIA is a novel A-kinase-anchoring protein.
AB  - To gain an insight into the cellular function of the unconventional myosin VIIA,
      we sought proteins interacting with its tail region, using the yeast two-hybrid
      system. Here we report on one of the five candidate interactors we identified,
      namely the type I alpha regulatory subunit (RI alpha) of protein kinase A. The
      interaction of RI alpha with myosin VIIA tail was demonstrated by
      coimmunoprecipitation from transfected HEK293 cells. Analysis of deleted
      constructs in the yeast two-hybrid system showed that the interaction of myosin
      VIIA with RI alpha involves the dimerization domain of RI alpha. In vitro binding
      assays identified the C-terminal "4.1, ezrin, radixin, moesin" (FERM)-like domain
      of myosin VIIA as the interacting domain. In humans and mice, mutations in the
      myosin VIIA gene underlie hereditary hearing loss, which may or may not be
      associated with visual deficiency. Immunohistofluorescence revealed that myosin
      VIIA and RI alpha are coexpressed in the outer hair cells of the cochlea and rod
      photoreceptor cells of the retina. Our results strongly suggest that myosin VIIA
      is a novel protein kinase A-anchoring protein that targets protein kinase A to
      definite subcellular sites of these sensory cells.

PMID- 10889204
TI  - The carboxyl-terminal region of the retinoblastoma protein binds non
      competitively to protein phosphatase type 1alpha and inhibits catalytic activity.
AB  - pRB, a negative-growth regulatory protein, is a demonstrated substrate for type 1
      serine/threonine protein phosphatases (PP1). In a recent report from this
      laboratory, we demonstrated that select forms of phosphorylated as well as
      hypophosphorylated pRB can be found complexed with the alpha-isotype of PP1
      (PP1alpha). This complex can also be observed when PP1 is rendered catalytically
      dead by toxin inhibition. These data suggested to us that pRB may bind to PP1 at
      one or more sites other than the catalytically active one on the enzyme and that
      such binding may play a role other than bringing the substrate into contact with
      the enzyme to facilitate catalysis. To address this possibility we utilized a
      series of pRB deletion mutants and coprecipitation studies to map the pRB domain
      involved in binding to PP1. Together with competition assays using in vivo
      expression of SV40 T-antigen, we show here that the carboxyl-terminal region of
      pRB is both necessary and sufficient for physical interaction with PP1.
      Subsequent biochemical analyses demonstrated inhibition of PP1 catalytic activity
      toward the standard substrate phosphorylase a when this enzyme is bound to pRB
      containing this region. K(m) and V(max) calculations revealed that pRB binds to
      PP1 in a non-competitive manner. These data support the notion that pRB, in
      addition to being a substrate for PP1, also functions as a PP1 inhibitor. The
      significance of this finding with respect to the functional importance of this
      interaction is discussed.

PMID- 10889205
TI  - Mechanism of electrogenic cation transport by the cloned organic cation
      transporter 2 from rat.
AB  - The organic cation transporter 2 (OCT2) is expressed in plasma membranes of
      kidney and brain. Its transport mechanism and substrates are debated. We studied
      substrate-induced changes of electrical current with the patch clamp technique
      after expression of rat OCT2 in oocytes. Activation of current, corresponding to
      efflux, was observed for small organic cations, e.g. choline. In contrast, the
      bigger cations quinine and tetrabutylammonium elicited no change in current.
      However, transport of choline could be inhibited by applying quinine or
      tetrabutylammonium to the cytoplasmic side. Inhibition of organic cation efflux
      by quinine was competitive with substrates. Quinine at the inside also inhibited
      substrate influx from the outside. Current-voltage analysis showed that both
      maximal turnover and apparent affinity to substrates are voltage-dependent.
      Substrate-induced currents with organic cations on both membrane sides reversed
      as predicted from the Nernst potential. Our results clearly identify the
      electrochemical potential as driving force for transport at neutral pH and
      exclude an electroneutral H(+)/organic cation(+) exchange. We suggest the
      existence of an electroneutral organic cation(+) exchange and propose a model for
      a carrier-type transport mechanism.

PMID- 10889206
TI  - Phosphatidylinositol is an essential phospholipid of mycobacteria.
AB  - Phosphatidylinositol (PI) and metabolically derived products such as the
      phosphatidylinositol mannosides and linear and mature branched lipomannan and
      lipoarabinomannan are prominent phospholipids/lipoglycans of Mycobacterium sp.
      believed to play important roles in the structure and physiology of the bacterium
      as well as during host infection. To determine if PI is an essential phospholipid
      of mycobacteria, we identified the pgsA gene of Mycobacterium tuberculosis
      encoding the phosphatidylinositol synthase enzyme and constructed a pgsA
      conditional mutant of Mycobacterium smegmatis. The ability of this mutant to
      synthesize phosphatidylinositol synthase and subsequently PI was dependent on the
      presence of a functional copy of the pgsA gene carried on a thermosensitive
      plasmid. The mutant grew like the control strain under permissive conditions (30
      degrees C), but ceased growing when placed at 42 degrees C, a temperature at
      which the rescue plasmid is lost. Loss of cell viability at 42 degrees C was
      observed when PI and phosphatidylinositol dimannoside contents dropped to
      approximately 30 and 50% of the wild-type levels, respectively. This work
      provides the first evidence of the essentiality of PI to the survival of
      mycobacteria. PI synthase is thus an essential enzyme of Mycobacterium that shows
      promise as a drug target for anti-tuberculosis therapy.

PMID- 10889207
TI  - The mechanism of ran import into the nucleus by nuclear transport factor 2.
AB  - The small GTPase Ran is essential for virtually all nucleocytoplasmic transport
      events. It is hypothesized that Ran drives vectorial transport of macromolecules
      into and out of the nucleus via the establishment of a Ran gradient between the
      cytoplasm and nucleoplasm. Although Ran shuttles between the nucleus and
      cytoplasm, it is concentrated in the nucleus at steady state. We show that
      nuclear transport factor 2 (NTF2) is required to concentrate Ran in the nucleus
      in the budding yeast, Saccharomyces cerevisiae. To analyze the mechanism of Ran
      import into the nucleus by NTF2, we use mutants in a variety of nuclear transport
      factors along with biochemical analyses of NTF2 complexes. We find that Ran
      remains concentrated in the nucleus when importin-mediated protein import is
      disrupted and demonstrate that NTF2 does not form a stable complex with the
      transport receptor, importin-beta. Consistent with a critical role for NTF2 in
      establishing and maintaining the Ran gradient, we show that NTF2 is required for
      early embryogenesis in Caenorhabditis elegans. Our data distinguish between two
      possible mechanisms for Ran import by NTF2 and demonstrate that Ran import is
      independent from importin-beta-mediated protein import.

PMID- 10889208
TI  - Exosite interactions determine the affinity of factor X for the extrinsic Xase
      complex.
AB  - The initiation of coagulation results from the activation of factor X by an
      enzyme complex (Xase) composed of the trypsin-like serine proteinase, factor
      VIIa, bound to tissue factor (TF) on phospholipid membranes. We have investigated
      the basis for the protein substrate specificity of Xase using TF reconstituted
      into vesicles of phosphatidylcholine, phosphatidylserine, or pure
      phosphatidylcholine. We show that occupation of the active site of VIIa within
      Xase by a reversible inhibitor or an alternate peptidyl substrate is sufficient
      to exclude substrate interactions at the active site but does not alter the
      affinity of Xase for factor X. This is evident as classical competitive
      inhibition of peptidyl substrate cleavage but as classical noncompetitive
      inhibition of factor X activation by active site-directed ligands. This implies
      that the productive recognition of factor X by Xase arises from a multistep
      reaction requiring an initial interaction at sites on the enzyme complex distinct
      from the active site (exosites), followed by active site interactions and bond
      cleavage. Exosite interactions determine protein substrate affinity, whereas the
      second binding step influences the maximum catalytic rate for the reaction. We
      also show that competitive inhibition can be achieved by interfering with exosite
      binding using factor X derivatives that are expected to have limited or abrogated
      interactions with the active site of VIIa within Xase. Thus, substrate
      interactions at exosites, sites removed from the active site of VIIa within the
      enzyme complex, determine affinity and binding specificity in the productive
      recognition of factor X by the VIIa-TF complex. This may represent a prevalent
      strategy through which distinctive protein substrate specificities are achieved
      by the homologous enzymes of coagulation.

PMID- 10889209
TI  - Glycosylation of GIRK1 at Asn119 and ROMK1 at Asn117 has different consequences
      in potassium channel function.
AB  - GIRK (G protein-gated inward rectifier K(+) channel) proteins play critical
      functional roles in heart and brain physiology. Using antibodies directed to
      either GIRK1 or GIRK4, site-directed mutagenesis, and specific glycosidases, we
      have investigated the effects of glycosylation in the biosynthesis and
      heteromerization of these proteins expressed in oocytes. Both GIRK1 and GIRK4
      have one extracellular consensus N-glycosylation site. Using chimeras between
      GIRK1 and GIRK4 as well as a GIRK1 N-glycosylation mutant, we report that GIRK1
      was glycosylated at Asn(119), whereas GIRK4 was not glycosylated at Asn(132).
      GIRK1 membrane-spanning domain 1 was required for optimal glycosylation at
      Asn(119) because a chimera that contained GIRK4 membrane-spanning domain 1
      significantly reduced the addition of a carbohydrate structure at this site. This
      finding may partly account for the reason that GIRK4 is not glycosylated at
      Asn(132), either as a homomer or when coexpressed with GIRK1. When the
      GIRK1(N119Q) mutant was coexpressed with GIRK4, the biophysical properties of the
      heteromeric channel and the magnitude of the agonist-induced currents were
      similar to those of controls. Thus, N-glycosylation of GIRK1 at Asn(119) does not
      appear to affect its physical association with GIRK4, the routing of the
      heteromer to the cell surface, or heteromeric channel function, unlike the
      dramatic functional effects of N-glycosylation of ROMK1 at Asn(117) (Schwalbe, R.
      A., Wang, Z., Wible, B. A., and Brown, A. M. (1995) J. Biol. Chem. 270, 15336
      15340).

PMID- 10889210
TI  - Activation of the luteinizing hormone receptor following substitution of Ser-277
      with selective hydrophobic residues in the ectodomain hinge region.
AB  - Glycoprotein hormone receptors are G protein-coupled receptors with ligand
      binding ectodomains consisting of leucine-rich repeats. The ectodomain is
      connected by a conserved cysteine-rich hinge region to the seven transmembrane
      (TM) region. Gain-of-function mutants of luteinizing hormone (LH) and thyroid
      stimulating hormone receptors found in patients allowed identification of
      residues important for receptor activation. Based on constitutively active
      mutations at Ser-281 in the hinge region of the thyroid-stimulating hormone
      receptor, we mutated the conserved serine in the LH (S277I) and follicle
      stimulating hormone receptors (S273I) and observed increased basal cAMP
      production and ligand affinity by mutant receptors. For the LH receptor,
      conversion of Ser-277 to all natural amino acids led to varying degrees of
      receptor activation. Hydropathy index analysis indicated that substitution of
      neutral serine with selective nonpolar hydrophobic residues (Leu>Val>Met>Ile)
      confers constitutive receptor activation whereas serine deletion or substitution
      with charged Arg, Lys, or Asp led to defective receptor expression. Furthermore,
      mutation of the angular proline near Ser-273 to flexible Gly also led to receptor
      activation. The findings suggest the ectodomain of glycoprotein hormone receptors
      constrain the TM region. Point mutations in the hinge region of these proteins,
      or ligand binding to these receptors, could cause conformational changes in the
      TM region that result in G(s) activation.

PMID- 10889211
TI  - Localization of the outer membrane subunit OprM of resistance-nodulation-cell
      division family multicomponent efflux pump in Pseudomonas aeruginosa.
AB  - The outer membrane subunit OprM of the multicomponent efflux pump of Pseudomonas
      aeruginosa has been assumed to form a transmembrane xenobiotic exit channel
      across the outer membrane. We challenged this hypothesis to clarify the
      underlying ambiguity by manipulating the amino-terminal signal sequence of the
      OprM protein of the MexAB-OprM efflux pump in P. aeruginosa. [(3)H]Palmitate
      uptake experiments revealed that OprM is a lipoprotein. The following lines of
      evidence unequivocally established that the OprM protein functioned at the
      periplasmic space. (i) The OprM protein, in which a signal sequence including Cys
      18 was replaced with that of periplasmic azurin, appeared in the periplasmic
      space but not in the outer membrane fraction, and the protein fully functioned as
      the pump subunit. (ii) The hybrid OprM containing the N-terminal transmembrane
      segment of the inner membrane protein, MexF, appeared exclusively in the inner
      membrane fraction. The hybrid protein containing 186 or 331 amino acid residues
      of MexF was fully active for the antibiotic extrusion, but a 42-residue protein
      was totally inactive. (iii) The mutant OprM, in which the N-terminal cysteine
      residue was replaced with another amino acid, appeared unmodified with fatty acid
      and was fractionated in both the periplasmic space and the inner membrane
      fraction but not in the outer membrane fraction. The Cys-18-modified OprM
      functioned for the antibiotic extrusion indistinguishably from that in the wild
      type strain. We concluded, based on these results, that the OprM protein was
      anchored in the outer membrane via fatty acid(s) attached to the N-terminal
      cysteine residue and that the entire polypeptide moiety was exposed to the
      periplasmic space.

PMID- 10889213
TI  - Removal of microsatellite interruptions by DNA replication slippage: phylogenetic
      evidence from Drosophila.
AB  - Microsatellites are tandem repetitions of short (1-6 bp) motifs. It is widely
      assumed that microsatellites degenerate through the accumulation of base
      substitutions in the repeat array. Using a phylogenetic framework, we studied the
      evolutionary dynamics of interruptions in three Drosophila microsatellite loci.
      For all three loci, we show that the interruptions in a microsatellite can be
      lost, resulting in a longer uninterrupted microsatellite stretch. These results
      indicate that mutations in the microsatellite array do not necessarily lead to
      decay but may represent only a transition state during the evolution of a
      microsatellite. Most likely, this purification of interrupted microsatellites is
      caused by DNA replication slippage.

PMID- 10889212
TI  - Enolase from Trypanosoma brucei, from the amitochondriate protist Mastigamoeba
      balamuthi, and from the chloroplast and cytosol of Euglena gracilis: pieces in
      the evolutionary puzzle of the eukaryotic glycolytic pathway.
AB  - Genomic or cDNA clones for the glycolytic enzyme enolase were isolated from the
      amitochondriate pelobiont Mastigamoeba balamuthi, from the kinetoplastid
      Trypanosoma brucei, and from the euglenid Euglena gracilis. Clones for the
      cytosolic enzyme were found in all three organisms, whereas Euglena was found to
      also express mRNA for a second isoenzyme that possesses a putative N-terminal
      plastid-targeting peptide and is probably targeted to the chloroplast. Database
      searching revealed that Arabidopsis also possesses a second enolase gene that
      encodes an N-terminal extension and is likely targeted to the chloroplast. A
      phylogeny of enolase amino acid sequences from 6 archaebacteria, 24 eubacteria,
      and 32 eukaryotes showed that the Mastigamoeba enolase tended to branch with its
      homologs from Trypanosoma and from the amitochondriate protist Entamoeba
      histolytica. The compartment-specific isoenzymes in Euglena arose through a gene
      duplication independent of that which gave rise to the compartment-specific
      isoenzymes in Arabidopsis, as evidenced by the finding that the Euglena enolases
      are more similar to the homolog from the eubacterium Treponema pallidum than they
      are to homologs from any other organism sampled. In marked contrast to all other
      glycolytic enzymes studied to date, enolases from all eukaryotes surveyed here
      (except Euglena) are not markedly more similar to eubacterial than to
      archaebacterial homologs. An intriguing indel shared by enolase from eukaryotes,
      from the archaebacterium Methanococcus jannaschii, and from the eubacterium
      Campylobacter jejuni maps to the surface of the three-dimensional structure of
      the enzyme and appears to have occurred at the same position in parallel in
      independent lineages.

PMID- 10889214
TI  - Structure and phylogeny of the venom group I phospholipase A(2) gene.
AB  - Phospholipases A(2) (PLA(2)s) catalyzing the hydrolysis of phospholipids form a
      family of proteins with diverse physiological and pharmacological properties.
      While there have been several reports on the cloning of PLA(2) cDNAs, very few
      studies have been carried out on the PLA(2) genes and, most importantly, no
      information has been available on the gene structure and function of group I
      venom PLA(2). This study, on the PLA(2) gene from a spitting cobra, besides being
      the very first report on any venom group I PLA(2) gene, constitutes the missing
      link in the biology and evolution of phospholipases. The 4-kb gene consists of
      four exons and three introns and resembles the human pancreatic PLA(2) gene.
      However, the size of intron 3 in particular is much smaller than that in the
      pancreatic gene. Interestingly, the information for the toxic and most of the
      pharmacological properties of the venom PLA(2) can be attributed to the end of
      exon 3 and the whole of exon 4 of the gene. This functional delineation fits in
      well with the theory of adaptive evolution exhibited by the venom PLA(2)s. We
      also show that the mammalian pancreatic and elapid PLA(2)s have similar paths of
      evolution (probably following gene duplication) from a common ancestral gene.
      Venom group II phospholipases, although evolved from the same ancestor, diverged
      early in evolution from the group I PLA(2) genes. Intriguingly, CAT reporter gene
      assays and DNase 1 footprinting studies on the promoter and its deletion
      constructs using CHO and HepG2 cell lines identified the possible involvement of
      cis elements such as Sp1, AP2, gamma-IRE, and (TG)(12) repeats in the expression
      of the gene in a tissue-specific manner.

PMID- 10889215
TI  - Lineage-specific evolutionary rate in mammalian mtDNA.
AB  - The existence of a lineage-specific nucleotide substitution rate in mammalian
      mtDNA has been investigated by analyzing the mtDNA of all available species, that
      is, 35 complete mitochondrial genomes from 14 mammalian orders. A detailed study
      of their evolutionary dynamics has been carried out on both ribosomal RNA and
      first and second codon positions (P12) of H-strand protein-coding genes by using
      two different types of relative-rate tests. Results are quite congruent between
      ribosomal and P12 sites. Significant rate variations have been observed among
      orders and among species of the same order. However, rate variation does not
      exceed 1.8-fold between the fastest (Proboscidea and Primates) and the slowest
      (Perissodactyla) evolving orders. Thus, the observed mitochondrial rate
      variations among taxa do not invalidate the suitability of mtDNA for drawing
      mammalian phylogeny. Dependence of evolutionary rate differences on variations in
      mutation and/or fixation rates was examined. Body size, generation time, and
      metabolic rate were tested, and no significant correlation was observed between
      them and the taxon-specific evolutionary rates, most likely because the latter
      might be influenced by multiple overlapping variable constraints.

PMID- 10889216
TI  - Elongation factor 1-alpha sequences do not support an early divergence of the
      Acoela.
AB  - The phylogenetic position of the Acoela is a key problem in the understanding of
      metazoan evolution. Recent studies based on 18S ribosomal DNA (rDNA) sequences
      have placed the Acoela in an extremely basal position as the sister group to all
      other extant triploblastic animals, suggesting that the phylum Platyhelminthes is
      polyphyletic. In order to test the results obtained with 18S rDNA, we sequenced
      elongation factor 1-alpha (EF1a) for the acoel Convoluta roscoffensis and five
      species of Turbellaria (two polyclads, Leptoplana tremellaris, and Prostheceraeus
      vittatus, and three triclads, Crenobia alpina, Schmidtea polychroa, and Girardia
      tigrina). Phylogenetic analyses of EF1a sequences show that the acoel sequences
      branch within the Platyhelminthes, in opposition to the 18S rDNA data. Moreover,
      comparison of the central variable region of EF1a shows similar sequence
      signatures between C. roscoffensis and the three triclad species. Although EF1a
      sequences fail to prove the monophyly of the phylum Platyhelminthes, they do not
      confirm the early divergence of the Acoela.

PMID- 10889217
TI  - Ty3/Gypsy retrotransposons: description of new Arabidopsis thaliana elements and
      evolutionary perspectives derived from comparative genomic data.
AB  - We performed a comprehensive analysis of the evolution of the Ty3/GYPSY: group of
      long-terminal-repeat retrotransposons (also known as METAVIRIDAE:). Exhaustive
      database searches allowed us to detect novel elements of this group. In
      particular, the Arabidopsis thaliana and Drosophila melanogaster genome
      sequencing projects have recently disclosed a large number of new Ty3/GYPSY:
      sequences. So far, elements of three different Ty3/GYPSY: lineages had been
      described for A. thaliana. Here, we describe six new lineages, which we have
      called Tit-for-tat1, Tit-for-tat2, Gimli, Gloin, Legolas, and Little Athila. We
      confirm that plant Ty3/GYPSY: elements form two main monophyletic groups.
      Moreover, our results suggest that at least four independent ancestral lineages
      existed before the monocot-dicot split, about 200 MYA. Twelve sequences from D.
      melanogaster that may correspond to new elements are also described. Some of
      these sequences are similar to those of OSVALDO: and Ulysses, two elements of the
      OSVALDO: clade that had never before been described for D. melanogaster.
      Comparative analyses of multiple organisms, some of them with completely
      sequenced genomes, show that the number of lineages of Ty3/GYPSY: elements is
      very variable. Thus, while only 1 lineage is present in Saccharomyces cerevisiae,
      at least 6 exist in Caenorhabditis elegans, at least 9 are present in the A.
      thaliana, and perhaps 20 are present in D. melanogaster. Finally, we suggest that
      the presence of a chromodomain-containing integrase, a feature of some closely
      related Ty3/GYPSY: elements of fungi, plants, and animals, may be used to define
      a new METAVIRIDAE: genus.

PMID- 10889218
TI  - Replicability and recurrence in the experimental evolution of a group I ribozyme.
AB  - In order to explore the variety of possible responses available to a ribozyme
      population evolving a novel phenotype, five Tetrahymena thermophila group I
      intron ribozyme pools were evolved in parallel for cleavage of a DNA
      oligonucleotide. These ribozyme populations were propagated under identical
      conditions and characterized when they reached apparent phenotypic plateaus; the
      populations that reached the highest plateau showed a near 100-fold improvement
      in DNA cleavage activity. A detailed characterization of the evolved response in
      these populations reveals at least two distinct phenotypic trajectories emerging
      as a result of the imposed selection. Not only do these distinct solutions
      exhibit differential DNA cleavage activity, but they also exhibit a very
      different correlation with a related, but unselected, phenotype: RNA cleavage
      activity. In turn, each of these trajectories is underwritten by differing
      genotypic profiles. This study underscores the complex network of possible
      trajectories through sequence space available to an evolving population and
      uncovers the diversity of solutions that result when the process of experimental
      evolution is repeated multiple times in a simple, engineered system.

PMID- 10889219
TI  - Evolution of cyclin-dependent kinases (CDKs) and CDK-activating kinases (CAKs):
      differential conservation of CAKs in yeast and metazoa.
AB  - Cyclin-dependent kinases (CDKs) function as central regulators of both the cell
      cycle and transcription. CDK activation depends on phosphorylation by a CDK
      activating kinase (CAK). Different CAKs have been identified in budding yeast,
      fission yeast, and metazoans. All known CAKs belong to the extended CDK family.
      The sole budding yeast CAK, CAK1, and one of the two CAKs in fission yeast, csk1,
      have diverged considerably from other CDKs. Cell cycle regulatory components have
      been largely conserved in eukaryotes; however, orthologs of neither CAK1 nor csk1
      have been identified in other species to date. To determine the evolutionary
      relationships of yeast and metazoan CAKs, we performed a phylogenetic analysis of
      the extended CDK family in budding yeast, fission yeast, humans, the fruit fly
      Drosophila melanogaster, and the nematode Caenorhabditis elegans. We observed
      that there were 10 clades for CDK-related genes, of which seven appeared
      ancestral, containing both yeast and metazoan genes. The four clades that contain
      CDKs that regulate transcription by phosphorylating the carboxyl-terminal domain
      (CTD) of RNA Polymerase II generally have only a single orthologous gene in each
      species of yeast and metazoans. In contrast, the ancestral cell cycle CDK
      (analogous to budding yeast CDC28) gave rise to a number of genes in metazoans,
      as did the ancestor of budding yeast PHO85. One ancestral clade is unique in that
      there are fission yeast and metazoan members, but there is no budding yeast
      ortholog, suggesting that it was lost subsequent to evolutionary divergence.
      Interestingly, CAK1 and csk1 branch together with high bootstrap support values.
      We used both the relative apparent synapomorphy analysis (RASA) method in
      combination with the S-F method of sampling reduced character sets and gamma
      corrected distance methods to confirm that the CAK1/csk1 association was not an
      artifact of long-branch attraction. This result suggests that CAK1 and csk1 are
      orthologs and that a central aspect of CAK regulation has been conserved in
      budding and fission yeast. Although there are metazoan CDK-family members for
      which we could not define ancestral lineage, our analysis failed to identify
      metazoan CAK1/csk1 orthologs, suggesting that if the CAK1/csk1 gene existed in
      the metazoan ancestor, it has not been conserved.

PMID- 10889221
TI  - Estimation of primate speciation dates using local molecular clocks.
AB  - Protein-coding genes of the mitochondrial genomes from 31 mammalian species were
      analyzed to estimate the speciation dates within primates and also between rats
      and mice. Three calibration points were used based on paleontological data: one
      at 20-25 MYA for the hominoid/cercopithecoid divergence, one at 53-57 MYA for the
      cetacean/artiodactyl divergence, and the third at 110-130 MYA for the
      metatherian/eutherian divergence. Both the nucleotide and the amino acid
      sequences were analyzed, producing conflicting results. The global molecular
      clock was clearly violated for both the nucleotide and the amino acid data.
      Models of local clocks were implemented using maximum likelihood, allowing
      different evolutionary rates for some lineages while assuming rate constancy in
      others. Surprisingly, the highly divergent third codon positions appeared to
      contain phylogenetic information and produced more sensible estimates of primate
      divergence dates than did the amino acid sequences. Estimated dates varied
      considerably depending on the data type, the calibration point, and the
      substitution model but differed little among the four tree topologies used. We
      conclude that the calibration derived from the primate fossil record is too
      recent to be reliable; we also point out a number of problems in date estimation
      when the molecular clock does not hold. Despite these obstacles, we derived
      estimates of primate divergence dates that were well supported by the data and
      were generally consistent with the paleontological record. Estimation of the
      mouse-rat divergence date, however, was problematic.

PMID- 10889220
TI  - Multiple nuclear insertions of mitochondrial cytochrome b sequences in
      callitrichine primates.
AB  - We report the presence of four nuclear paralogs of a 380-bp segment of cytochrome
      b in callitrichine primates (marmosets and tamarins). The mitochondrial
      cytochrome b sequence and each nuclear paralog were obtained from several
      species, allowing multiple comparisons of rates and patterns of substitution both
      between mitochondrial and nuclear sequences and among nuclear sequences. The
      mitochondrial DNA had high overall rates of molecular evolution and a strong bias
      toward substitutions at third codon positions. Rates of molecular evolution among
      the nuclear sequences were low and constant, and there were small differences in
      substitution patterns among the nuclear clades which were probably attributable
      to the small number of sites involved. A novel method of phylogenetic
      reconstruction based on the large difference in rates of evolution at different
      codon positions among mitochondrial and nuclear clades was used to determine
      whether different nuclear paralogs represent independent transposition events or
      duplications following a single insertion. This method is generally applicable in
      cases where differences in pattern of molecular evolution are known, and it
      showed that at least three of the four nuclear clades represent independent
      transposition events. The insertion events giving rise to two of the nuclear
      clades predate the divergence of the callitrichines, whereas those leading to the
      other two nuclear clades may have occurred in the common ancestor of marmosets.

PMID- 10889222
TI  - Mitochondrial sequence evolution in spiders: intraspecific variation in tRNAs
      lacking the TPsiC Arm.
AB  - Analyses of mitochondrial DNA sequences from three species of Habronattus jumping
      spiders (Chelicerata: Arachnida: Araneae) reveal unusual inferred tRNA secondary
      structures and gene arrangements, providing new information on tRNA evolution
      within chelicerate arthropods. Sequences from the protein-coding genes NADH
      dehydrogenase subunit 1 (ND1), cytochrome oxidase subunit I (COI), and subunit II
      (COII) were obtained, along with tRNA, tRNA, and large-subunit ribosomal RNA
      (16S) sequences; these revealed several peculiar features. First, inferred
      secondary structures of tRNA and, likely, tRNA, lack the TPsiC arm and the
      variable arm and therefore do not form standard cloverleaf structures. In place
      of these arms is a 5-6-nt T arm-variable loop (TV) replacement loop such as that
      originally described from nematode mitochondrial tRNAs. Intraspecific variation
      occurs in the acceptor stem sequences in both tRNAs. Second, while the proposed
      secondary structure of the 3' end of 16S is similar to that reported for insects,
      the sequence at the 5' end is extremely divergent, and the entire gene is
      truncated about 300 nt with respect to Drosophila yakuba. Third, initiation
      codons appear to consist of ATY (ATT and ATC) and TTG for ND1 and COII,
      respectively. Finally, Habronattus shares the same ND1-tRNA-16S gene arrangement
      as insects and crustaceans, thus illustrating variation in a tRNA gene
      arrangement previously proposed as a character distinguishing chelicerates from
      insects and crustaceans.

PMID- 10889223
TI  - Comparative evolution of the mitochondrial cytochrome b gene and nuclear beta
      fibrinogen intron 7 in woodpeckers.
AB  - Most molecular phylogenetic studies of vertebrates have been based on DNA
      sequences of mitochondrial-encoded genes. MtDNA evolves rapidly and is thus
      particularly useful for resolving relationships among recently evolved groups.
      However, it has the disadvantage that all of the mitochondrial genes are
      inherited as a single linkage group so that only one independent gene tree can be
      inferred regardless of the number of genes sequenced. Introns of nuclear genes
      are attractive candidates for independent sources of rapidly evolving DNA: they
      are pervasive, most of their nucleotides appear to be unconstrained by selection,
      and PCR primers can be designed for sequences in adjacent exons where nucleotide
      sequences are conserved. We sequenced intron 7 of the beta-fibrinogen gene (beta
      fibint7) for a diversity of woodpeckers and compared the phylogenetic signal and
      nucleotide substitution properties of this DNA sequence with that of
      mitochondrial-encoded cytochrome b (cyt b) from a previous study. A few indels
      (insertions and deletions) were found in the beta-fibint7 sequences, but
      alignment was not difficult, and the indels were phylogentically informative. The
      beta-fibint7 and cyt b gene trees were nearly identical to each other but
      differed in significant ways from the traditional woodpecker classification. Cyt
      b evolves 2.8 times as fast as beta-fibint7 (14. 0 times as fast at third codon
      positions). Despite its relatively slow substitution rate, the phylogenetic
      signal in beta-fibint7 is comparable to that in cyt b for woodpeckers, because
      beta-fibint7 has less base composition bias and more uniform nucleotide
      substitution probabilities. As a consequence, compared with cyt b, beta-fibint7
      nucleotide sites are expected to enter more distinct character states over the
      course of evolution and have fewer multiple substitutions and lower levels of
      homoplasy. Moreover, in contrast to cyt b, in which nearly two thirds of
      nucleotide sites rarely vary among closely related taxa, virtually all beta
      fibint7 nucleotide sites appear free of selective constraints, which increases
      informative sites per unit sequenced. However, the estimated gamma distribution
      used to model rate variation among sites suggests constraints on some beta
      fibint7 sites. This study suggests that introns will be useful for phylogenetic
      studies of recently evolved groups.

PMID- 10889224
TI  - Molecular evolution and phylogeny of the buzzatii complex (Drosophila repleta
      group): a maximum-likelihood approach.
AB  - The buzzatii complex of the mulleri subgroup (Drosophila repleta group) consists
      of three clusters of species whose evolutionary relationships are poorly known.
      We analyzed 2,085 coding nucleotides from the xanthine dehydrogenase (XDH:) gene
      in the 10 available species of the complex and Drosophila mulleri and Drosophila
      hydei. We adopted a statistical model-fitting approach within the maximum
      likelihood (ML) framework of phylogenetic inference. We first modeled the process
      of nucleotide substitution using a tree topology which was reasonably accurate.
      Then we used the most satisfactory description so attained to reconstruct the
      evolutionary relationships in the buzzatii complex. We found that a minimally
      realistic description of the substitution process of XDH: should allow six
      substitution types and different substitution rates for codon positions. Using
      this description we obtained a strongly supported, fully resolved tree which is
      congruent with the already-known (yet few) relationships. We also analyzed
      published data from three mitochondrial cytochrome oxidases (CO I, II, and III).
      In our analyses, these relatively short DNA sequences failed to discriminate
      statistically among alternative phylogenies. When the data of these three gene
      regions are combined with the XDH: sequences, the phylogenetic signal emerging
      from XDH: becomes reinforced. All four of the gene regions evolve faster in the
      buzzatii and martensis clusters than in the stalkeri cluster, paralleling the
      amount of chromosomal evolution.

PMID- 10889225
TI  - Phylogenies inferred from mitochondrial gene orders-a cautionary tale from the
      parasitic flatworms.

PMID- 10889226
TI  - When one is not enough: introgression of mitochondrial DNA in Drosophila.

PMID- 10889227
TI  - Impact factors and citation rates in plant physiology.

PMID- 10889228
TI  - Positional cloning in Arabidopsis. Why it feels good to have a genome initiative
      working for you.
AB  - Positional (or map-based) cloning techniques are widely used to identify the
      protein products of genes defined by mutation. In Arabidopsis the information
      generated by the Genome Initiative is giving this approach a decisive boost. A
      wealth of sequence polymorphisms and molecular markers is now available and can
      be exploited for fine mapping with technically simple and robust polymerase chain
      reaction-based methods. As a result it has become possible to complete positional
      cloning projects in a short time and with relatively little effort.

PMID- 10889229
TI  - Mass spectrometry. An essential tool in proteome analysis.

PMID- 10889230
TI  - How do plant mitochondria avoid importing chloroplast proteins? Components of the
      import apparatus Tom20 and Tom22 from Arabidopsis differ from their fungal
      counterparts.

PMID- 10889231
TI  - Enzyme redundancy and the importance of 2-oxoglutarate in higher plant ammonium
      assimilation.

PMID- 10889232
TI  - Phytochelatins and their roles in heavy metal detoxification.

PMID- 10889233
TI  - Blue light activates potassium-efflux channels in flexor cells from Samanea saman
      motor organs via two mechanisms.
AB  - Light-induced leaflet movement of Samanea saman depends on the regulation of
      membrane transporters in motor cells. Blue light (BL) stimulates leaflet opening
      by inducing K(+) release from the flexor motor cells. To elucidate the mechanism
      of K(+)-efflux (K(D))-channel regulation by light, flexor motor cell protoplasts
      were patch-clamped in a cell-attached configuration during varying illumination.
      Depolarization elicited outward currents through single open K(D) channels.
      Changes in cell membrane potential (E(M)) were estimated by applying voltage
      ramps and tracking the change of the apparent reversal potential of K(D)-channel
      current. BL shifted E(M) in a positive direction (i.e. depolarized the cell) by
      about 10 mV. Subsequent red light pulse followed by darkness shifted E(M)
      oppositely (i.e. hyperpolarized the cell). The BL-induced shifts of E(M) were not
      observed in cells pretreated with a hydrogen-pump inhibitor, suggesting a
      contribution by hydrogen-pump to the shift. BL also increased K(D)-channel
      activity in a voltage-independent manner as reflected in the increase of the mean
      net steady-state patch conductance at a depolarization of 40 mV relative to the
      apparent reversal potential (G(@40)). G(@40) increased by approximately 12 pS
      without a change of the single-channel conductance, possibly by increasing the
      probability of channel opening. Subsequent red-light and darkness reversed the
      change in G(@40). Thus, K(+) efflux, a determining factor for the cell-volume
      decrease of flexor cells, is regulated by BL in a dual manner via membrane
      potential and by an independent signaling pathway.

PMID- 10889234
TI  - Mtsym6, a gene conditioning Sinorhizobium strain-specific nitrogen fixation in
      Medicago truncatula.
AB  - The availability of a wide range of independent lines for the annual medic
      Medicago truncatula led us to search for natural variants in the symbiotic
      association with Sinorhizobium meliloti. Two homozygous lines, Jemalong 6 and
      DZA315.16, originating from an Australian cultivar and a natural Algerian
      population, respectively, were inoculated with two wild-type strains of S.
      meliloti, RCR2011 and A145. Both plant lines formed nitrogen-fixing (effective)
      nodules with the RCR2011 strain. However, the A145 strain revealed a nitrogen
      fixation polymorphism, establishing an effective symbiosis (Nod(+)Fix(+)) with
      DZA315.16, whereas only small, white, non-nitrogen fixing nodules (Nod(+)Fix(-))
      were elicited on Jemalong 6. Cytological studies demonstrated that these non
      fixing nodules are encircled by an endodermis at late stages of development, with
      no visible meristem, and contain hypertrophied and autofluorescent infection
      threads, suggesting the induction of plant defense reactions. The non-fixing
      phenotype is independent of growth conditions and determined by a single
      recessive allele (Mtsym6), which is located on linkage group 8.

PMID- 10889235
TI  - Cell-specific and conditional expression of caffeoyl-coenzyme A-3-O
      methyltransferase in poplar.
AB  - Caffeoyl coenzyme A-3-O-methyltransferase (CCoAOMT) plays an important role in
      lignin biosynthesis and is encoded by two genes in poplar (Populus trichocarpa).
      Here, we describe the expression pattern conferred by the two CCoAOMT promoters
      when fused to the gus-coding sequence in transgenic poplar (Populus tremula x
      Populus alba). Both genes were expressed similarly in xylem and differentially in
      phloem. In xylem, expression was preferentially observed in vessels and contact
      rays, whereas expression was barely detectable in storage rays and fibers,
      suggesting different routes to monolignol biosynthesis in the different xylem
      types. Furthermore, after wounding, fungal infection, and bending, the expression
      of both genes was induced concomitantly with de novo lignin deposition.
      Importantly, upon bending and leaning of the stem, the cell-specific expression
      pattern was lost, and both genes were expressed in all cell types of the xylem.
      CCoAOMT promoter activity correlated well with the presence of the CCoAOMT
      protein, as shown by immunolocalization. These expression data may explain, at
      least in part, the heterogeneity in lignin composition that is observed between
      cell types and upon different environmental conditions.

PMID- 10889236
TI  - Analysis of gene promoters for two tomato polygalacturonases expressed in
      abscission zones and the stigma.
AB  - The tomato (Lycopersicon esculentum cv Ailsa Craig) polygalacturonase genes TAPG1
      (LYCes;Pga1;2) and TAPG4 (LYCes;Pga1;5) are abundantly expressed in both
      abscission zones and the pistils of mature flowers. To further investigate the
      spatial and temporal expression patterns for these genes, the TAPG gene promoters
      were ligated to beta-glucuronidase (GUS) reporter genes and transformed into
      tomato. GUS expression with both constructs was similar and entirely consistent
      with the expression patterns of the native gene transcripts. GUS activity was
      observed in the weakening abscission zones of the leaf petiole, flower and fruit
      pedicel, flower corolla, and fruit calyx. In leaf petiole and flower pedicel
      zones this activity was enhanced by ethylene and inhibited by indole-3-acetic
      acid. On induction of abscission with ethylene, GUS accumulation was much earlier
      in TAPG4:GUS than in TAPG1:GUS transformants. Moreover, TAPG4:GUS staining
      appeared to predominate in the vascular bundles relative to surrounding cortex
      cells whereas TAPG1:GUS was more evenly distributed across the separation layer.
      Like the native genes, GUS was also expressed in the stigma. Activity was not
      apparent in pistils until the flowers had opened and was confined to the stigma
      and style immediately proximal to it. A minimal promoter construct consisting of
      a 247-bp 5'-upstream element from TAPG1 was found to be sufficient to direct GUS
      expression in both abscission zones and the stigma.

PMID- 10889237
TI  - Complementary expression of two plastid-localized sigma-like factors in maize.
AB  - The eubacterial-like RNA polymerase of plastids is composed of organelle-encoded
      core subunits and nuclear-encoded sigma-factors. Families of sigma-like factors
      (SLFs) have been identified in several plants, including maize (Zea mays) and
      Arabidopsis. In vitro import assays determined that at least two of the maize
      sigma-like proteins have functional chloroplast transit peptides and thus are
      likely candidates for chloroplast transcriptional regulators. However, the roles
      of individual SLFs in chloroplast transcription remain to be determined. We have
      raised antibodies against the unique amino-terminal domains of two maize SLFs,
      ZmSig1 and ZmSig3, and have used these specific probes to examine the
      accumulation of each protein in different maize tissues and during chloroplast
      development. The expression of ZmSig1 is tissue specific and parallels the light
      activated chloroplast development program in maize seedling leaves. Its
      accumulation in mature chloroplasts however, is not affected by subsequent
      changes in the light regime. It is interesting that the expression profile of
      ZmSig3 is complementary to that of ZmSig1. It accumulates in non-green tissues,
      including roots, etiolated seedling leaves, and the basal region of greening
      seedling leaves. The nonoverlapping expression patterns of these two plastid
      localized SLFs suggest that they may direct differential expression of plastid
      genes during chloroplast development.

PMID- 10889238
TI  - Female reproductive tissues are the primary target of Agrobacterium-mediated
      transformation by the Arabidopsis floral-dip method.
AB  - The floral-dip method for Agrobacterium-mediated transformation of Arabidopsis
      allows efficient plant transformation without need for tissue culture. To
      facilitate use with other plant species, we investigated the mechanisms that
      underlie this method. In manual outcrossing experiments, application of
      Agrobacterium tumefaciens to pollen donor plants did not produce any transformed
      progeny, whereas application of Agrobacterium to pollen recipient plants yielded
      transformants at a rate of 0.48%. Agrobacterium strains with T-DNA carrying gusA
      (encoding beta-glucuronidase [GUS]) under the control of 35S, LAT52, or ACT11
      promoters revealed delivery of GUS activity to developing ovules, whereas no GUS
      staining of pollen or pollen tubes was observed. Transformants derived from the
      same seed pod contained independent T-DNA integration events. In Arabidopsis
      flowers, the gynoecium develops as an open, vase-like structure that fuses to
      form closed locules roughly 3 d prior to anthesis. In correlation with this fact,
      we found that the timing of Agrobacterium infection was critical. Transformants
      were obtained and GUS staining of ovules and embryo sacs was observed only if the
      Agrobacterium were applied 5 d or more prior to anthesis. A 6-fold higher rate of
      transformation was obtained with a CRABS-CLAW mutant that maintains an open
      gynoecium. Our results suggest that ovules are the site of productive
      transformation in the floral-dip method, and further suggest that Agrobacterium
      must be delivered to the interior of the developing gynoecium prior to locule
      closure if efficient transformation is to be achieved.

PMID- 10889239
TI  - CHRK1, a chitinase-related receptor-like kinase in tobacco.
AB  - A cDNA encoding a chitinase-related receptor-like kinase, designated CHRK1, was
      isolated from tobacco (Nicotiana tabacum). The C-terminal kinase domain (KD) of
      CHRK1 contained all of the conserved amino acids of serine/threonine protein
      kinases. The putative extracellular domain was closely related to the class V
      chitinase of tobacco and to microbial chitinases. CHRK1 mRNA accumulation was
      strongly stimulated by infection with fungal pathogen and tobacco mosaic virus.
      Amino acid-sequence analysis revealed that the chitinase-like domain of CHRK1
      lacked the essential glutamic acid residue required for chitinase activity. The
      recombinant chitinase-like domain did not show any catalytic activity for either
      oligomeric or polymeric chitin substrates. The recombinant KD of CHRK1 exhibited
      autophosphorylation, but the mutant KD with a mutation in the essential ATP
      binding site did not, suggesting that CHRK1 encoded a functional kinase. CHRK1
      was detected in membrane fractions of tobacco BY2 cells. Furthermore, CHRK1-GFP
      fusion protein was localized in plasma membranes when it was expressed in animal
      cells. This is the first report of a new type of receptor-like kinase containing
      a chitinase-like sequence in the putative extracellular domain.

PMID- 10889240
TI  - A matrix metalloproteinase gene is expressed at the boundary of senescence and
      programmed cell death in cucumber.
AB  - Cell-cell and extracellular cell matrix (ECM) interactions provide cells with
      information essential for controlling morphogenesis, cell-fate specification, and
      cell death. In animals, one of the major groups of enzymes that degrade the ECM
      is the matrix metalloproteinases (MMPs). Here, we report the characterization of
      the cucumber (Cucumis sativus L. cv Marketmore) Cs1-MMP gene encoding such an
      enzyme likely to play a role in plant ECM degradation. Cs1-MMP has all the
      hallmark motif characteristics of animal MMPs and is a pre-pro-enzyme having a
      signal peptide, propeptide, and zinc-binding catalytic domains. Cs1-MMP also
      displays functional similarities with animal MMPs. For example, it has a
      collagenase-like activity that can cleave synthetic peptides and type-I collagen,
      a major component of animal ECM. Cs1-MMP activity is completely inhibited by a
      hydroxamate-based inhibitor that binds at the active site of MMPs in a
      stereospecific manner. The Cs1-MMP gene is expressed de novo at the end stage of
      developmental senescence, prior to the appearance of DNA laddering in cucumber
      cotyledons leaf discs and male flowers. As the steady-state level of Cs1-MMP mRNA
      peaks late in senescence and the pro-enzyme must undergo maturation and
      activation, the protease is probably not involved in nutrient remobilization
      during senescence but may have another function. The physiological substrates for
      Cs1-MMP remain to be determined, but the enzyme represents a good candidate for
      plant ECM degradation and may be involved in programmed cell death (PCD). Our
      results suggest that PCD occurs only at the culmination of the senescence program
      or that the processes are distinct with PCD being triggered at the end of
      senescence.

PMID- 10889241
TI  - Identification of phloem involved in assimilate loading in leaves by the activity
      of the galactinol synthase promoter.
AB  - The definition of "minor" veins in leaves is arbitrary and of uncertain
      biological significance. Generally, the term refers to the smallest vein classes
      in the leaf, believed to function in phloem loading. We found that a galactinol
      synthase promoter, cloned from melon (Cucumis melo), directs expression of the
      gusA gene to the smallest veins of mature Arabidopsis and cultivated tobacco
      (Nicotiana tabacum) leaves. This expression pattern is consistent with the role
      of galactinol synthase in sugar synthesis and phloem loading in cucurbits. The
      expression pattern in tobacco is especially noteworthy since galactinol is not
      synthesized in the leaves of this plant. Also, we unexpectedly found that
      expression in tobacco is limited to two of three companion cells in class-V
      veins, which are the most extensive in the leaf. Thus, the "minor" vein system is
      defined and regulated at the genetic level, and there is heterogeneity of
      response to this system by different companion cells of the same vein.

PMID- 10889242
TI  - Glucose and disaccharide-sensing mechanisms modulate the expression of alpha
      amylase in barley embryos.
AB  - The aim of this study was to investigate the sugar-sensing processes modulating
      the expression of alpha-amylase in barley (Hordeum vulgaris L. var Himalaya)
      embryos. The results highlight the existence of independent glucose (Glc) and
      disaccharides sensing. Glc treatment destabilizes the alpha-amylase mRNA. Non
      metabolizable disaccharides repress alpha-amylase induction, but have no effects
      on transcript stability. Structure-function analysis indicates that a fructose
      (Fru) moiety is needed for disaccharide sensing. Lactulose (beta-galactose
      [Gal][1-->4]Fru), palatinose (Glc[1-->6]Fru), and turanose (Glc[1-->3]Fru) are
      not metabolized but repress alpha-amylase. Disrupting the fructosyl moiety of
      lactulose and palatinose, or replacing the Fru moiety of beta-Gal[1-->4]Fru with
      Glc or Gal results in molecules unable to repress alpha-amylase. Comparison of
      the molecular requirements for sucrose transport with those for disaccharide
      sensing suggests that these sugars are perceived possibly at the plasma membrane
      level independently from sucrose transport.

PMID- 10889243
TI  - A glucosinolate mutant of Arabidopsis is thermosensitive and defective in
      cytosolic Hsp90 expression after heat stress.
AB  - The TU8 mutant of Arabidopsis previously described to be deficient in
      glucosinolate metabolism and pathogen-induced auxin accumulation was found to be
      remarkably less tolerant upon exposure to elevated temperatures than wild-type
      plants. Although moderately increased temperature only affected shoot growth,
      exposure to severe heat stress led to a dramatic decay of mutant plants. By
      contrast, wild-type seedlings showed little or no damage under the same
      conditions. Analysis of different heat stress proteins (Hsps) in TU8 seedlings
      revealed that only expression of cytoplasmic Hsp90 was affected in these plants.
      Although Hsp90 was present under control conditions, its level declined in mutant
      plants at elevated temperatures. Northern-blot analysis indicated that the
      decrease in Hsp90 protein was accompanied with a reduction of hsp90 transcript
      levels. Transient expression of Hsp90 in mutant protoplasts increased their
      survival rate at higher temperatures to near equivalent that of wild-type
      protoplasts. These data suggest that the reduced level of Hsp90 in TU8 mutants
      may be the primary cause for the observed reduction in thermostability.

PMID- 10889244
TI  - Compression wood-responsive proteins in developing xylem of maritime pine (Pinus
      pinaster ait.).
AB  - When a conifer shoot is displaced from its vertical position, compression wood
      (CW) is formed on the under side and can eventually return the shoot to its
      original position. Changes in cell wall structure and chemistry associated with
      CW are likely to result from differential gene/protein expression. Two
      dimensional polyacrylamide gel electrophoresis of differentiating xylem proteins
      was combined with the physical characterization of wooden samples to identify and
      characterize CW-responsive proteins. Differentiating xylem was harvested from a
      22-year-old crooked maritime pine (Pinus pinaster Ait.) tree. Protein extracted
      from different samples were revealed by high-resolution silver stained two
      dimensional polyacrylamide gel electrophoresis and analyzed with a computer
      assisted system for single spot quantification. Growth strain (GS) measurements
      allowed xylem samples to be classified quantitatively from normal wood to CW.
      Regression of lignin and cellulose content on GS showed that an increase in the
      percentage of lignin and a decrease of the percentage of cellulose corresponded
      to increasing GS values, i.e. CW. Of the 137 studied spots, 19% were
      significantly associated with GS effect. Up-regulated proteins included 1
      aminocyclopropane-1-carboxylate oxidase (an ethylene forming enzyme), a putative
      transcription factor, two lignification genes (caffeic O-methyltransferase and
      caffeoyl CoA-O-methyltransferase), members of the S-adenosyl-L-methionine
      synthase gene family, and enzymes involved in nitrogen and carbon assimilation
      (glutamine synthetase and fructokinase). A clustered correlation analysis was
      performed to study simultaneously protein expression along a gradient of
      gravistimulated stressed xylem tissue. Proteins were found to form "expression
      clusters" that could identify: (a) Gene product under similar control mechanisms,
      (b) partner proteins, or (c) functional groups corresponding to specialized
      pathways. The possibility of obtaining regulatory correlations and
      anticorrelations between proteins provide us with a new category of homology
      (regulatory homology) in tracing functional relationships.

PMID- 10889245
TI  - Regulation of ethylene biosynthesis in response to pollination in tomato flowers.
AB  - Pollination of many flowers leads to an increase in ethylene synthesis and flower
      senescence. We have investigated the regulation of pollination-induced ethylene
      synthesis in tomato (Lycopersicon esculentum) using flowers of the dialytic (dl)
      mutant, in which pollination can be manipulated experimentally, with the aim of
      developing a model system to study tomato flower senescence. Ethylene synthesis
      increased rapidly in dl pistils following pollination, leading to accelerated
      petal senescence, and was delayed in ethylene-insensitive Never-ripe (Nr)
      pistils. However, Nr pistils eventually produced more ethylene than dl pistils,
      suggesting the presence of negative feedback regulation of ethylene synthesis
      following pollination. LEACS1A expression correlated well with increased ethylene
      production in pollinated dl pistils, and expression in Nr revealed that
      regulation is via an ethylene-independent mechanism. In contrast, the induction
      of the 1-aminocyclopropane-1-carboxylic acid oxidases, LEACO1 and LEACO3,
      following pollination is ethylene dependent. In addition, the expression profiles
      of ACS and ACO genes were determined during petal senescence and a hypothesis
      proposed that translocated 1-aminocyclopropane-1-carboxylic acid from the pistil
      may be important for regulating the initial burst of ethylene production during
      petal senescence. These results are discussed and differences between tomato and
      the ornamental species previously studied are highlighted.

PMID- 10889246
TI  - The regulation of 1-aminocyclopropane-1-carboxylic acid synthase gene expression
      during the transition from system-1 to system-2 ethylene synthesis in tomato.
AB  - 1-Aminocyclopropane-1-carboxylic acid synthase (ACS) is one of the key regulatory
      enzymes involved in the synthesis of the hormone ethylene and is encoded by a
      multigene family containing at least eight members in tomato (Lycopersicon
      esculentum). Increased ethylene production accompanies ripening in tomato, and
      this coincides with a change in the regulation of ethylene synthesis from auto
      inhibitory to autostimulatory. The signaling pathways that operate to bring about
      this transition from so-called system-1 to system-2 ethylene production are
      unknown, and we have begun to address these by investigating the regulation of
      ACS expression during ripening. Transcripts corresponding to four ACS genes,
      LEACS1A, LEACS2, LEACS4, and LEACS6, were detected in tomato fruit, and
      expression analysis using the ripening inhibitor (rin) mutant in combination with
      ethylene treatments and the Never-ripe (Nr) mutant has demonstrated that each is
      regulated in a unique way. A proposed model suggests that system-1 ethylene is
      regulated by the expression of LEACS1A and LEACS6. In fruit a transition period
      occurs in which the RIN gene plays a pivotal role leading to increased expression
      of LEACS1A and induction of LEACS4. System-2 ethylene synthesis is subsequently
      initiated and maintained by ethylene-dependent induction of LEACS2.

PMID- 10889247
TI  - Direct measurement of aluminum uptake and distribution in single cells of Chara
      corallina.
AB  - Quantitative information on the uptake and distribution of Al at the cellular
      level is required to understand mechanisms of Al toxicity, but direct measurement
      of uptake across the plasma membrane has remained elusive. We measured rates of
      Al transport across membranes in single cells of Chara corallina using the rare
      (26)Al isotope, an emerging technology (accelerator mass spectrometry), and a
      surgical technique for isolating subcellular compartments. Accumulation of Al in
      the cell wall dominated total uptake (71-318 microgram m(-2) min(-1)), although
      transport across the plasma membrane was detectable (71-540 ng m(-2) min(-1))
      within 30 min of exposure. Transport across the tonoplast was initially
      negligible, but accelerated to rates approximating uptake across the plasma
      membrane. The avacuolate protoplasm showed signs of saturation after 60 min, but
      continued movement across the plasma membrane was supported by sequestration in
      the vacuole. Saturation of all compartments was observed after 12 to 24 h.
      Accumulation of Al in the cell wall reflected variation in [Al(3+)] induced by
      changes in Al supply or complexing ligands, but was unaffected by pH. In
      contrast, transport across the plasma membrane peaked at pH 4.3 and increased
      when [Al(3+)] was reduced by complexing ligands. Cold temperature (4 degrees C)
      reduced accumulation in the cell wall and protoplasm, whereas 2,4-dinitrophenol
      and m-chlorocarbonylcyanidephenyl hydrazone increased membrane transport by 12-
      to 13-fold. Our data suggest that the cell wall is the major site of Al
      accumulation. Nonetheless, membrane transport occurs within minutes of exposure
      and is supported by subsequent sequestration in the vacuole. The rapid delivery
      of Al to the protoplasm suggests that intracellular lesions may be possible.

PMID- 10889248
TI  - Involvement of brassinosteroids in the gravitropic response of primary root of
      maize.
AB  - Exogenously applied brassinolide (BL, 10(-9)-10(-5) M) increased gravitropic
      curvature in maize (Zea mays) primary roots. The BL-enhanced gravitropic
      curvature was clearly promoted in the presence of indole-3-acetic acid (IAA, 10(
      10)-10(-8) M), indicating that BL is interactive with IAA during the gravitropic
      response. The interactive effect between BL and IAA was completely diminished by
      treatment of p-chlorophenoxy isobutric acid, an auxin action antagonist. The
      activation of the gravitropic response by BL in the absence and in the presence
      of IAA was nullified by application of 2, 3,5-triiodobenzoic acid, a polar auxin
      transport inhibitor. The data indicate that brassinosteroids (BRs) might be
      involved in auxin-mediated processes for the gravitropic response. Gas
      chromotography-selected ion-monitoring analysis revealed that maize primary roots
      contained approximately 0.3 ng g(-1) fresh weight castasterone as an endogenous
      BR. Exogenously applied castasterone also increased the gravitropic response of
      maize roots in an IAA-dependent manner. This study provides the first evidence,
      to our knowledge, for occurrence and gravitropic activity of BRs in plant roots.

PMID- 10889249
TI  - Tissue-preferential expression of a rice alpha-tubulin gene, OsTubA1, mediated by
      the first intron.
AB  - The genomic clone encoding an alpha-tubulin, OsTubA1, has been isolated from rice
      (Oryza sativa L.). The gene consists of four exons and three introns. RNA-blot
      analysis showed that the gene is strongly expressed in actively dividing tissues,
      including root tips, young leaves, and young flowers. Analysis of chimeric
      fusions between OsTubA1 and beta-glucuronidase (GUS) revealed that the intron 1
      was required for high-level GUS expression in actively dividing tissues,
      corresponding with normal expression pattern of OsTubA1. Fusion constructs
      lacking the intron 1 showed more GUS staining in mature tissues rather than young
      tissues. When the intron 1 was placed at the distal region from 5'-upstream
      region or at the 3'-untranslated region, no enhancement of GUS expression was
      observed. Sequential deletions of the OsTubA1 intron 1 brought about a gradual
      reduction of GUS activity in calli. These results suggest that tissue
      preferential expression of the OsTubA1 gene is mediated by the intron 1 and that
      it may be involved in a mechanism for an efficient RNA splicing that is position
      dependent.

PMID- 10889250
TI  - Bordered pit structure and vessel wall surface properties. Implications for
      embolism repair.
AB  - The idea that embolized xylem vessels can be refilled while adjacent vessels
      remain under tension is difficult to accept if the cavitated vessels remain
      hydraulically connected to vessels under tension. A mechanism by which embolized
      conduits could be hydraulically isolated from adjacent conduits requires the
      existence of a non-zero contact angle and a flared opening into the bordered pit
      chamber such that a convex air-water interface forms at the entrance into the pit
      chamber. We measured the contact angle and pit chamber geometry for six species.
      The contact angle measured in the vessel lumen ranged between 42 degrees to 55
      degrees, whereas the opening into the pit chamber ranged between 144 degrees and
      157 degrees. If the surface properties within the pit chamber are similar to
      those in the lumen, a convex meniscus will form at the flared opening into the
      pit chamber. The maximum pressure difference between water in the lumen and gas
      in the pit chamber that could be stabilized by this interface was calculated to
      be within the range of 0.07 to 0.30 MPa.

PMID- 10889251
TI  - Increases in water potential gradient reduce xylem conductivity in whole plants.
      Evidence from a low-pressure conductivity method.
AB  - A new method using hydrostatic suctions (less than 0.02 MPa) was used to measure
      whole-root conductivity (K(r)) in saplings of two angiosperm pioneer trees
      (Eucalyptus regnans and Toona australis) and two rainforest conifers (Dacrycarpus
      dacrydioides and Nageia fleurii). The resultant K(r) was combined with
      measurements of stem and leaf hydraulic conductivity to calculate whole-plant
      conductivity and to predict leaf water potential (Psi(l)) during transpiration.
      At normal soil temperatures there was good agreement between measured and
      predicted Psi(l) during transpiration in all species. Changes in the soil-to-leaf
      water potential gradient were produced by root chilling, and in three of the four
      species, changes in Psi(l) corresponded to those expected by the effect of
      increased water viscosity on K(r). In one species, however, root chilling
      produced severe plant wilting and a decline in Psi(l) significantly below the
      predicted value. In this species Psi(l) decreased to a value close to, or below,
      the Psi(l) at 50% xylem cavitation. It is concluded that decreased whole-plant
      conductivity in T. australis resulted from a decrease in xylem conductivity due
      to stress-induced cavitation.

PMID- 10889252
TI  - Azuki bean cells are hypersensitive to cadmium and do not synthesize
      phytochelatins.
AB  - Suspension-cultured cells of azuki bean (Vigna angularis) as well as the original
      root tissues were hypersensitive to Cd (<10 microM). Repeated subculturings with
      a sublethal level of Cd (1-10 microM) did not affect the subsequent response of
      cells to inhibitory levels of Cd (10-100 microM). The azuki bean cells challenged
      to Cd did not contain phytochelatin (PC) peptides, unlike tomato (Lycopersicon
      esculentum) cells that have a substantial tolerance to Cd (>100 microM). Both of
      the cell suspensions contained a similar level of reduced glutathione (GSH) when
      grown in the absence of Cd. Externally applied GSH to azuki bean cells recovered
      neither Cd tolerance nor PC synthesis of the cells. Furthermore, enzyme assays in
      vitro revealed that the protein extracts of azuki bean cells had no activity
      converting GSH to PCs, unlike tomato. These results suggest that azuki bean cells
      are lacking in the PC synthase activity per se, hence being Cd hypersensitive. We
      concluded that the PC synthase has an important role in Cd tolerance of
      suspension-cultured cells.

PMID- 10889253
TI  - Differential interaction of maize root ferredoxin:NADP(+) oxidoreductase with
      photosynthetic and non-photosynthetic ferredoxin isoproteins.
AB  - In higher plants ferredoxin (Fd):NADP(+) oxidoreductase (FNR) and Fd are each
      distributed in photosynthetic and non-photosynthetic organs as distinct
      isoproteins. We have cloned cDNAs for leaf FNR (L-FNR I and L-FNR II) and root
      FNR (R-FNR) from maize (Zea mays L.), and produced recombinant L-FNR I and R-FNR
      to study their enzymatic functions through kinetic and Fd-binding analyses. The
      K(m) value obtained by assay for a diaphorase activity indicated that R-FNR had a
      10-fold higher affinity for NADPH than L-FNR I. When we assayed for NADPH
      cytochrome c reductase activity using maize photosynthetic Fd (Fd I) and non
      photosynthetic Fd (Fd III), the R-FNR showed a marked difference in affinity
      between these two Fd isoproteins; the K(m) for Fd III was 3.0 microM and that for
      Fd I was 29 microM. Consistent with this, the dissociation constant for the R
      FNR:Fd III complex was 10-fold smaller than that of the R-FNR:Fd I complex. This
      differential binding capacity was confirmed by an affinity chromatography of R
      FNR on Fd-sepharose with stronger binding to Fd III. L-FNR I showed no such
      differential interaction with Fd I and Fd III. These data demonstrated that R-FNR
      has the ability to discriminate between these two types of Fds. We propose that
      the stronger interaction of R-FNR with Fd III is crucial for an efficient
      electron flux of NADPH-FNR-Fd cascade, thus supporting Fd-dependent metabolism in
      non-photosynthetic organs.

PMID- 10889254
TI  - Ionic and osmotic effects of NaCl-induced inactivation of photosystems I and II
      in Synechococcus sp.
AB  - We report here that osmotic effects and ionic effects are both involved in the
      NaCl-induced inactivation of the photosynthetic machinery in the cyanobacterium
      Synechococcus sp. PCC 7942. Incubation of the cyanobacterial cells in 0.5 M NaCl
      induced a rapid and reversible decline and subsequent slow and irreversible loss
      of the oxygen-evolving activity of photosystem (PS) II and the electron transport
      activity of PSI. An Na(+)-channel blocker protected both PSII and PSI against the
      slow, but not the rapid, inactivation. The rapid decline resembled the effect of
      1.0 M sorbitol. The presence of both an Na(+)-channel blocker and a water-channel
      blocker protected PSI and PSII against the short- and long-term effects of NaCl.
      Salt stress also decreased cytoplasmic volume and this effect was enhanced by the
      Na(+)-channel blocker. Our observations suggested that NaCl had both osmotic and
      ionic effects. The osmotic effect decreased the amount of water in the cytosol,
      rapidly increasing the intracellular concentration of salts. The ionic effect was
      caused by an influx of Na(+) ions through potassium/Na(+) channels that also
      increased concentrations of salts in the cytosol and irreversibly inactivated PSI
      and PSII.

PMID- 10889255
TI  - Purification and characterization of a membrane-associated 48-kilodalton
      phospholipase A(2) in leaves of broad bean.
AB  - Several lines of evidence indicate that phospholipase A(2) (PLA(2)) plays a
      crucial role in plant cellular responses through production of linolenic acid,
      the precursor of jasmonic acid, from membrane phospholipids. Here we report the
      purification and characterization of a 48-kD PLA(2) from the membrane fractions
      of leaves of broad bean (Vicia faba). The plant PLA(2) was purified to near
      homogeneity by sequential column chromatographies from the membrane extracts. The
      purified 48-kD protein migrated as a single band on a SDS-PAGE gel and its
      density correlated with the PLA(2) activity. It was further confirmed that this
      48-kD protein is the PLA(2) enzyme based on immunoprecipitating the activity with
      a monoclonal antibody against it and purifying the enzyme to homogeneity with the
      antibody affinity column. The purified plant PLA(2) preferred 2-linolenoyl-sn
      glycerol-3-phosphocholine (GPC) to 2-linoleoyl-GPC, 2-palmitoyl-GPC and 2
      arachidonyl-GPC as substrates with a pH optimum at pH 7.0 to 8.0. The plant
      PLA(2) was activated by calmodulin and inhibited by pretreatment of 5,8,11, 14
      eicosatetraynoic acid known as an inhibitor of mammalian PLA(2)s. The enzyme was
      characterized as a Ca(2+)-independent PLA(2) different from mammalian PLA(2)s.
      This membrane-associated and Ca(2+)-independent PLA(2) is suggested to play an
      important role in the release of linolenic acid, the precursor of jasmonic acid,
      through a signal transduction pathway.

PMID- 10889256
TI  - Increasing tryptophan synthesis in a forage legume Astragalus sinicus by
      expressing the tobacco feedback-insensitive anthranilate synthase (ASA2) gene.
AB  - A cDNA clone that encodes a feedback-insensitive anthranilate synthase (AS),
      ASA2, isolated from a 5-methyl-tryptophan (Trp) (5MT)-resistant tobacco cell line
      under the control of the constitutive cauliflower mosaic virus 35S promoter, was
      introduced into the forage legume Astragalus sinicus by Agrobacterium rhizogenes
      with kanamycin selection. The 35S-ASA2 gene was expressed constitutively as
      demonstrated by northern-blot hybridization analyses and the presence of feedback
      insensitive AS. Hairy root lines transformed with 35S-ASA2 grew in concentrations
      of up to 100 microM 5MT, whereas the controls were completely inhibited by 15
      microM 5MT. Expression of the feedback-insensitive ASA2 resulted in a 1.3- to 5.5
      fold increase in free Trp. Kinetic studies of the AS activity demonstrate the Trp
      feedback alterations and indicate that the ASA2 alpha-subunit can interact with
      the native A. sinicus beta-subunit to form an active enzyme. The ASA2 transcript
      and high free Trp were also detected in the leaves, stems, and roots of plants
      regenerated from the transformed hairy roots. Thus, we show for the first time
      that ASA2 can be used to transform plants of a different species to increase the
      levels of the essential amino acid Trp and impart 5MT resistance.

PMID- 10889257
TI  - Alteration of the adenine nucleotide response and increased Rubisco activation
      activity of Arabidopsis rubisco activase by site-directed mutagenesis.
AB  - Arabidopsis Rubisco was activated in vitro at rates 2- to 3-fold greater by
      recombinant Arabidopsis 43-kD Rubisco activase with the amino acid replacements
      Q111E and Q111D in a phosphate-binding loop, G-G-K-G-Q-G-K-S. However, these two
      mutant enzymes had only slightly greater rates of ATP hydrolysis. Activities of
      the Q111D enzyme were much less sensitive and those of Q111E were somewhat less
      sensitive to inhibition by ADP. Both mutant enzymes exhibited higher Rubisco
      activation activities over the physiological range of ADP to ATP ratios. Enzymes
      with non-polar, polar, and basic residues substituted at position Gln-111
      exhibited rates of Rubisco activation less than the wild-type enzyme. Estimates
      of the relative affinity of the wild type and the Q111D, Q111E, and Q111S enzymes
      for adenosine nucleotides by a variety of methods revealed that the nucleotide
      affinities were the most diminished in the Q111D enzyme. The temperature
      stability of the Q111D and Q111E enzymes did not differ markedly from that of the
      43-kD recombinant wild-type enzyme, which is somewhat thermolabile. The Q111D and
      Q111E enzymes, expressed in planta, may provide a means to better define the role
      of the ADP to ATP ratio in the regulation of Rubisco activation and
      photosynthesis rate.

PMID- 10889258
TI  - Characterization of sulfate assimilation in marine algae focusing on the enzyme
      5'-adenylylsulfate reductase.
AB  - 5'-Adenylylsulfate (APS) reductase was characterized in diverse marine algae. A
      cDNA encoding APS reductase from Enteromorpha intestinalis (EAPR) was cloned by
      functional complementation of an Escherichia coli cysH mutant. The deduced amino
      acid sequence shows high homology with APS reductase (APR) from flowering plants.
      Based on the probable transit peptide cleavage site the mature protein is 45.7
      kD. EAPR expressed as a His-tagged recombinant protein catalyzes reduced
      glutathione-dependent reduction of APS to sulfite, exhibiting a specific activity
      of approximately 40 micromol min(-1) mg protein(-1) and Michealis-Menten kinetic
      constants of approximately 1.4 mM for reduced glutathione and approximately 6.5
      microM for APS. APR activity and expression were studied in relation to the
      production of 3-dimethylsulfoniopropionate (DMSP), a sulfonium compound produced
      by many marine algae. A diverse group of DMSP-producing species showed extremely
      high enzyme activity (up to 400 times that found in flowering plants). Antibodies
      raised against a conserved peptide of APR strongly cross-reacted with a protein
      of 45 kD in several chlorophytes but insignificantly with chromophytes. In the
      chlorophyte Tetraselmis sp., APR activity varies significantly during the culture
      cycle and does not follow the changes in cellular DMSP content. However, a
      positive correlation was found between cell-based APR activity and specific
      growth rate.

PMID- 10889259
TI  - Isolation and characterization of plant N-acetyl glucosaminyltransferase I (GntI)
      cDNA sequences. Functional analyses in the Arabidopsis cgl mutant and in
      antisense plants.
AB  - We report on the isolation and characterization of full-length cDNA sequences
      coding for N-acetylglucosaminyltransferase I (GnTI) from potato (Solanum
      tuberosum L.), tobacco (Nicotiana tabacum L.), and Arabidopsis. The deduced
      polypeptide sequences show highest homology among the solanaceous species (93%
      identity between potato and tobacco compared with about 75% with Arabidopsis) but
      share only weak homology with human GnTI (35% identity). In contrast to the
      corresponding enzymes from animals, all plant GnTI sequences identified are
      characterized by a much shorter hydrophobic membrane anchor and contain one
      putative N-glycosylation site that is conserved in potato and tobacco, but
      differs in Arabidopsis. Southern-blot analyses revealed that GntI behaves as a
      single-copy gene. Northern-blot analyses showed that GntI-mRNA expression is
      largely constitutive. Arabidopsis cgl mutants deficient in GnTI activity also
      possess GntI mRNA, indicating that they result from point mutations. GntI
      expression constructs were tested for the ability to relieve the GnTI block in
      protoplasts of the Arabidopsis cgl mutant and used to obtain transgenic potato
      and tobacco plants that display a substantial reduction of complex glycan
      patterns. The latter observation indicates that production of heterologous
      glycoproteins with little or no antigenic glycans can be achieved in whole
      plants, and not in just Arabidopsis, using antisense technology.

PMID- 10889260
TI  - Auxin biosynthesis in maize kernels.
AB  - Auxin biosynthesis was analyzed in a maize (Zea mays) kernel culture system in
      which the seeds develop under physiological conditions similar to the in vivo
      situation. This system was modified for precursor feeding experiments. Tryptophan
      (Trp) is efficiently incorporated into indole-3-acetic acid (IAA) with retention
      of the 3, 3' bond. Conversion of Trp to IAA is not competed by indole. Labeling
      with the general precursors [U-(13)C(6)]glucose and [1, 2-(13)C(2)]acetate
      followed by retrobiosynthetic analysis strongly suggest that Trp-dependent IAA
      synthesis is the predominant route for auxin biosynthesis in the maize kernel.
      The synthesis of IAA from indole glycerol phosphate and IAA formation via
      condensation of indole with an acetyl-coenzyme A or phosphoenolpyruvate derived
      metabolite can be excluded.

PMID- 10889261
TI  - Acquired thermotolerance and expression of the HSP100/ClpB genes of lima bean.
AB  - Acquired thermotolerance (AT) is the ability of cells to survive a normally
      lethal temperature treatment as a consequence of pretreatment at an elevated but
      sublethal temperature. In yeast and cyanobacteria, the expression of the
      HSP100/ClpB protein is required for the AT response. To determine whether the
      HSP100/ClpB protein is associated with this response in lima bean (Phaseolus
      lunatus), we have cloned an HSP100/ClpB homolog and assessed expression of the
      two gene copies under heat stress conditions, which induce AT. Transcription of
      the cytoplasmically localized HSP100/ClpB protein genes is stringently controlled
      by heat stress in both of the laboratory and field heat stress conditions. From a
      heat-induced cDNA library, we identified a clone of a putative chloroplast
      targeted (cp) HSP100/ClpB protein gene sequence. The cp HSP100/ClpB protein genes
      are constitutively expressed, but transcript levels increase post-heat stress in
      laboratory heat stress experiments. In field conditions the genes for the cp
      HSP100/ClpB are constitutively expressed. Although we were unable to correlate
      differences in the timing of AT response with the expression or genetic structure
      of the HSP100/ClpB genes in heat-tolerant or -sensitive varieties of lima bean,
      we clearly demonstrate the association of expression of HSP100/ClpB proteins with
      heat response in this species.

PMID- 10889262
TI  - Identification of natural rubber and characterization of rubber biosynthetic
      activity in fig tree.
AB  - Natural rubber was extracted from the fig tree (Ficus carica) cultivated in Korea
      as part of a survey of rubber producing plants. Fourier transform infrared and
      (13)C nuclear magnetic resonance analysis of samples prepared by successive
      extraction with acetone and benzene confirmed that the benzene-soluble residues
      are natural rubber, cis-1,4-polyisoprene. The rubber content in the latex of fig
      tree was about 4%, whereas the rubber content in the bark, leaf, and fruit was
      0.3%, 0.1%, and 0.1%, respectively. Gel-permeation chromatography revealed that
      the molecular size of the natural rubber from fig tree is about 190 kD. Similar
      to rubber tree (Hevea brasiliensis) and guayule (Parthenium argentatum Gray),
      rubber biosynthesis in fig tree is tightly associated with rubber particles. The
      rubber transferase in rubber particles exhibited a higher affinity for farnesyl
      pyrophosphate than for isopentenyl pyrophosphate, with apparent K(m) values of
      2.8 and 228 microM, respectively. Examination of latex serum from fig tree by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed major proteins
      of 25 and 48 kD in size, and several proteins with molecular mass below 20 and
      above 100 kD. Partial N-terminal amino acid sequencing and immunochemical
      analyses revealed that the 25- and 48-kD proteins were novel and not related to
      any other suggested rubber transferases. The effect of EDTA and Mg(2+) ion on in
      vitro rubber biosynthesis in fig tree and rubber tree suggested that divalent
      metal ion present in the latex serum is an important factor in determining the
      different rubber biosynthetic activities in fig tree and rubber tree.

PMID- 10889263
TI  - Elevated CO(2) induces biochemical and ultrastructural changes in leaves of the
      C(4) cereal sorghum.
AB  - We analyzed the impact of growth at either 350 (ambient) or 700 (elevated) microL
      L(-1) CO(2) on key elements of the C(4) pathway (photosynthesis, carbon isotope
      discrimination, and leaf anatomy) using the C(4) cereal sorghum (Sorghum bicolor
      L. Moench.). Gas-exchange analysis of the CO(2) response of photosynthesis
      indicated that both carboxylation efficiency and the CO(2) saturated rate of
      photosynthesis were lower in plants grown at elevated relative to ambient CO(2).
      This was accompanied by a 49% reduction in the phosphoenolpyruvate carboxylase
      content of leaves (area basis) in the elevated CO(2)-grown plants, but no change
      in Rubisco content. Despite the lower phosphoenolpyruvate carboxylase content,
      there was a 3-fold increase in C isotope discrimination in leaves of plants grown
      at elevated CO(2) and bundle sheath leakiness was estimated to be 24% and 33%,
      respectively, for the ambient and elevated CO(2)-grown plants. However, we could
      detect no difference in quantum yield. The ratio of quantum yield of CO(2)
      fixation to PSII efficiency was lower in plants grown at elevated CO(2), but only
      when leaf internal was below 50 microL L(-1). This suggests a reduction in the
      efficiency of the C(4) cycle when [CO(2)] is low, and also implies increased
      electron transport to acceptors other than CO(2). Analysis of leaf sections using
      a transmission electron microscope indicated a 2-fold decrease in the thickness
      of the bundle sheath cell walls in plants grown at elevated relative to ambient
      CO(2). These results suggest that significant acclimation to increased CO(2)
      concentrations occurs in sorghum.

PMID- 10889264
TI  - Biochemical evidence for two novel enzymes in the biosynthesis of 3
      dimethylsulfoniopropionate in Spartina alterniflora.
AB  - 3-Dimethylsulfoniopropionate (DMSP) is an osmoprotectant accumulated by the
      cordgrass Spartina alterniflora and other salt-tolerant plants. Previous in vivo
      isotope tracer and metabolic modeling studies demonstrated that S. alterniflora
      synthesizes DMSP via the route S-methyl-Met --> 3-dimethylsulfoniopropylamine
      (DMSP-amine) --> 3-dimethylsulfoniopropionaldehyde --> DMSP and indicated that
      the first reaction requires a far higher substrate concentration than the second
      to attain one-half-maximal rate. As neither of these reactions is known from
      other organisms, two novel enzymes are predicted. Two corresponding activities
      were identified in S. alterniflora leaf extracts using specific radioassays. The
      first, S-methyl-Met decarboxylase (SDC), strongly prefers the L-enantiomer of S
      methyl-Met, is pyridoxal 5'-phosphate-dependent, generates equimolar amounts of
      CO(2) and DMSP-amine, and has a high apparent K(m) (approximately 18 mM) for its
      substrate. The second enzyme, DMSP-amine oxidase (DOX), requires O(2) for
      activity, shows an apparent K(m) for DMSP-amine of 1.8 mM, and is not accompanied
      by DMSP-amine dehydrogenase or transaminase activity. Very little SDC or DOX
      activity was found in grasses lacking DMSP. These data indicate that SDC and DOX
      are the predicted novel enzymes of DMSP synthesis.

PMID- 10889265
TI  - beta-Cyanoalanine synthase is a mitochondrial cysteine synthase-like protein in
      spinach and Arabidopsis.
AB  - beta-Cyano-alanine synthase (CAS; EC 4.4.1.9) plays an important role in cyanide
      metabolism in plants. Although the enzymatic activity of beta-cyano-Ala synthase
      has been detected in a variety of plants, no cDNA or gene has been identified so
      far. We hypothesized that the mitochondrial cysteine synthase (CS; EC 4.2.99. 8)
      isoform, Bsas3, could actually be identical to CAS in spinach (Spinacia oleracea)
      and Arabidopsis. An Arabidopsis expressed sequence tag database was searched for
      putative Bsas3 homologs and four new CS-like isoforms, ARAth;Bsas1;1,
      ARAth;Bsas3;1, ARAth;Bsas4;1, and ARAth;Bsas4;2, were identified in the process.
      ARAth;Bsas3;1 protein was homologous to the mitochondrial SPIol;Bsas3;1 isoform
      from spinach, whereas ARAth;Bsas4;1 and ARAth;Bsas4;2 proteins defined a new
      class within the CS-like proteins family. In contrast to spinach SPIol;Bsas1;1
      and SPIol;Bsas2;1 recombinant proteins, spinach SPIol;Bsas3;1 and Arabidopsis
      ARAth;Bsas3;1 recombinant proteins exhibited preferred substrate specificities
      for the CAS reaction rather than for the CS reaction, which identified these
      Bsas3 isoforms as CAS. Immunoblot studies supported this conclusion. This is the
      first report of the identification of CAS synthase-encoding cDNAs in a living
      organism. A new nomenclature for CS-like proteins in plants is also proposed.

PMID- 10889267
TI  - Exploiting secondary growth in Arabidopsis. Construction of xylem and bark cDNA
      libraries and cloning of three xylem endopeptidases.
AB  - The root-hypocotyl of Arabidopsis produces a relatively large amount of secondary
      vascular tissue when senescence is delayed by the removal of inflorescences, and
      plants are grown at low population density. Peptidase zymograms prepared from
      isolated xylem and phloem revealed the existence of distinct proteolytic enzyme
      profiles within these tissues. cDNA libraries were constructed from isolated
      xylem and bark of the root-hypocotyl and screened for cDNAs coding for cysteine,
      serine, and aspartic peptidases. Three cDNAs, two putative papain-type cysteine
      peptidases (XCP1 and XCP2) and one putative subtilisin-type serine peptidase
      (XSP1), were identified from the xylem library for further analysis. Using RNA
      gel blots it was determined that these peptidases were expressed in the xylem and
      not in the bark. Quantitative reverse transcriptase-polymerase chain reaction
      confirmed the RNA gel-blot results and revealed high levels of XCP1 and XCP2 mRNA
      in stems and flowers of the infloresence. A poly-histidine-tagged version of XCP1
      was purified from Escherichia coli by denaturing metal-chelate chromatography.
      Following renaturation, the 40-kD recombinant XCP1 was not proteolytically
      active. Activation was achieved by incubation of recombinant XCP1 at pH 5.5 and
      was dependent on proteolytic processing of the 40-kD inactive polypeptide to a 26
      kD active peptidase.

PMID- 10889266
TI  - A family of at least seven beta-galactosidase genes is expressed during tomato
      fruit development.
AB  - During our search for a cDNA encoding beta-galactosidase II, a beta
      galactosidase/exogalactanase (EC 3.2.1.23) present during tomato (Lycopersicon
      esculentum Mill.) fruit ripening, a family of seven tomato beta-galactosidase
      (TBG) cDNAs was identified. The shared amino acid sequence identity among the
      seven TBG clones ranged from 33% to 79%. All contained the putative active site
      containing consensus sequence pattern G-G-P-[LIVM]-x-Q-x-E-N-E-[FY] belonging to
      glycosyl hydrolase family 35. Six of the seven single-copy genes were mapped
      using restriction fragment length polymorphisms of recombinant inbred lines. RNA
      gel-blot analysis was used to evaluate TBG mRNA levels throughout fruit
      development, in different fruit tissues, and in various plant tissues. RNA gel
      blot analysis was also used to reveal TBG mRNA levels in fruit of the rin, nor,
      and Nr tomato mutants. The TBG4-encoded protein, known to correspond to beta
      galactosidase II, was expressed in yeast and exo-galactanase activity was
      confirmed via a quantified release of galactosyl residues from cell wall
      fractions containing beta(1-->4)-D-galactan purified from tomato fruit.

PMID- 10889268
TI  - Radiotherapy-Associated Anemia: The Scope of the Problem.
AB  - The impact of anemia on cancer patients undergoing chemotherapy is well
      established, but only recently has the prevalence of anemia in patients receiving
      radiotherapy received much attention. Many cancer patients present with anemia
      prior to radiotherapy, and even more experience anemia or a worsening of anemia
      at some point during treatment. However, the problem of anemia is often ignored
      because patients may experience only functional anemia, defined as a hemoglobin
      level less than 12 g/dl. Unless physiologic anemia (hemoglobin = 8 g/dl) is
      discovered, efforts to correct anemia are often not made. Because hemoglobin
      levels <12 g/dl seem to be associated with tumor hypoxia and poorer outcomes of
      radiotherapy in a number of patient populations, ignoring even modest anemia can
      result in decreased locoregional control, overall survival, and quality of life
      (QOL). Because increasing hemoglobin levels 1-2 g/dl is usually easily
      accomplished, there exists the potential for improving outcomes by paying greater
      attention to this problem. This article focuses on the prevalence of anemia,
      particularly functional anemia, and discusses the impact of anemia on
      locoregional control, overall survival, and QOL.

PMID- 10889269
TI  - The Impact of Fatigue on Patients with Cancer: Overview of FATIGUE 1 and 2.
AB  - Fatigue is a complex, multifactorial disorder with physical, mental, and
      psychological dimensions that has been associated with diminished quality of life
      (QOL) in patients with cancer. The prevalence and severity of fatigue, however,
      has only recently been studied systematically. Two national surveys commissioned
      by The Fatigue Coalition, a multidisciplinary group of medical practitioners,
      researchers, and patient advocates, whose mission is to study the importance of
      fatigue for patients with cancer and their caregivers, have assessed the
      prevalence, severity, and QOL consequences of fatigue in patients with cancer.
      The most recent survey, initiated in 1998, sought to confirm and extend
      observations on the prevalence and impact of fatigue in patients with cancer as
      part of an initiative to develop guidelines for the differential diagnosis and
      treatment of fatigue. The FATIGUE 2 study probed the emotional, social, physical,
      and economic impact of fatigue on patients with cancer and their caregivers.
      Patient perceptions of the professional response to cancer-related fatigue were
      also assessed. The key findings of these surveys are reviewed. 2000;5(suppl 2): 9
      12

PMID- 10889270
TI  - Impact of Anemia in Patients With Head and Neck Cancer.
AB  - Head and neck squamous cell carcinoma, which is comprised of a heterogeneous
      group of tumors arising from the epithelial lining of the oral cavity, pharynx,
      and larynx, is a locoregional disease. Tumor hypoxia and anemia are known to
      adversely effect the efficacy of radiation therapy, a local treatment modality.
      Therefore, head and neck cancers represent an ideal model for assessing the
      impact of anemia following treatment with radiation therapy. Various treatment
      strategies aimed at increasing tumor oxygenation in head and neck cancer patients
      (including hyperbaric oxygen and hypoxic cell radiosensitizers) have been
      studied. These studies have been fueled by evidence that hypoxia adversely
      effects the radiosensitivity of cells. Although the exact mechanism of action of
      the oxygen effect is not known, in vitro studies with conventional photon
      radiation therapy under normoxic conditions have shown an effectiveness of 2.5
      3.0 times greater than that achieved under anoxic conditions. Recent studies,
      including large retrospective analyses, have demonstrated the dramatic adverse
      impact of anemia upon locoregional tumor control and survival. These studies,
      which have revealed hemoglobin levels as a powerful prognostic factor, provide
      compelling evidence for the value of reversing anemia and hence tumor hypoxia in
      head and neck cancer patients.

PMID- 10889271
TI  - The Relationship between Anemia and Quality of Life in Cancer Patients.
AB  - Anemia is a common occurrence in patients with cancer, and especially in those
      who undergo chemotherapy. Traditionally, significantly decreased hemoglobin
      levels have been considered to be </= 8 g/dl and have been associated with
      physiologic manifestations. More recent data have shown that milder anemia
      (hemoglobin levels 10-12 g/dl) has functional consequences as well. This article
      reviews several communitybased studies that have analyzed changes in hemoglobin
      concentrations, transfusion requirements, and QOL parameters in anemic patients
      with cancer before and after treatment with epoetin alfa. The results of these
      studies have been consistent and show an increase in hemoglobin and a reduction
      in transfusion requirements when compared with baseline. Furthermore, a
      relationship between increasing hemoglobin levels and an improvement in QOL is
      suggested that is independent of tumor response. Additional studies are
      evaluating the optimal hemoglobin levels for the greatest incremental improvement
      in QOL.

PMID- 10889273
TI  - Fractionation of cells and subcellular particles with Percoll.
AB  - At present, centrifugation is the most common method for separation and isolation
      of cells and subcellular particles. The technique can be used for a wide range of
      applications. During latter years it has become obvious what a powerful method
      density gradient centrifugation is, especially when used in conjunction with
      sensitive assays or clinical treatments. The most active areas for use of density
      gradient centrifugation include purification for in vitro fertilization of sperm
      of both human and bovine origin, isolation of cells for cell therapy of patients
      receiving chemo- and radiation therapy and basic research both on cellular and
      subcellular levels. These treatments and investigations require homogeneous
      populations of cells and cell organelles, which are undamaged after the
      separation procedure. Percoll, once introduced to reduce convection during
      centrifugation, has proved to be the density gradient medium of choice since it
      fulfills almost all criteria of an ideal density gradient medium. Recently good
      results have also been obtained after silanization of colloidal silica particles,
      e.g. BactXtractor. The latter medium has proved to be useful in recovery of
      microorganisms from food samples free of inhibitors to the Polymer Chain Reaction
      (PCR). The separation procedures described for Percoll in this review seem to be
      applicable to any cells or organelles in suspension for which differences in size
      or bouyant density exist. Furthermore, since Percoll media are inert, they are
      well suited for the separation of fragile elements like enveloped viruses.

PMID- 10889272
TI  - A brief review of retinitis pigmentosa and the identified retinitis pigmentosa
      genes.
AB  - The family of inherited ocular diseases that is collectively known as retinitis
      pigmentosa is a major cause of progressive retinal disease worldwide. As such,
      this family of diseases has been the object of much scientific scrutiny, both
      clinical and basic. The recent application of molecular genetic analyses has
      heralded the rapid elucidation of the underlying gene defects in many cases. In
      this article, the fundamental clinical and electroretinographic characteristics
      of retinitis pigmentosa will be recalled. Additionally, the current understanding
      of the genetic causes of retinitis pigmentosa will be reviewed, and the
      identified causative genes will be classified into groups related by function.

PMID- 10889274
TI  - Analysis of radiation damage of DNA by atomic force microscopy in comparison with
      agarose gel electrophoresis studies.
AB  - DNA damage induced with ionizing radiation is considered one of the main causes
      of cell inactivation. Several methods including gel electrophoresis, pulsed-field
      gel electrophoresis, neutral filter elution method, neutral sedimentation and
      electron microscopy have been applied to analyze this type of DNA damage. A new
      method employing an atomic force microscope (AFM) for nanometer-level-structure
      analysis of DNA damage induced with gamma-irradiation is introduced in this
      report. Structural changes of plasmid DNA on a molecular size scale of about 3
      kbp were visually analyzed by AFM after irradiation with 60Co gamma-rays at doses
      of 1.9, 5.6, and 8.3 kGy. Three forms of plasmid DNA, closed circular (intact
      DNA), open circular (DNA with a single strand break) and linear form (DNA with a
      double strand break) were visualized by dynamic force mode AFM after gamma
      irradiation. The torsional feature of the plasmid DNA was visualized better with
      AFM than with a transmission electron microscope (TEM). All three forms of
      plasmid DNA were observed in the sample irradiated with gamma-rays at the dose of
      1.9 kGy. Open circular and linear forms were observed in the samples irradiated
      with gamma-rays at doses of 5.6 and 8.3 kGy, though no closed circular form was
      observed. A shortening of the length of a linear form of DNA irradiated with 5.6
      and 8.3 kGy gamma-rays was observed by AFM. Structural changes of DNA after gamma
      irradiation were visualized by AFM at nanometer level resolution. In addition,
      shortening of the length of the linear form of DNA after radiation exposure was
      observed by AFM.

PMID- 10889275
TI  - Interaction between hammerhead ribozyme and RNA substrates measured by a surface
      plasmon resonance biosensor.
AB  - Dynamic interactions between hammerhead ribozymes and RNA substrates were
      measured using the surface plasmon resonance (SPR) technology. Two in vitro
      transcribed substrates (non-cleavable and cleavable) were immobilised on
      streptavidin-coated dextran matrices and subsequently challenged with non-related
      yeast tRNA or two hammerhead ribozymes, both of which had previously been shown
      to exhibit functional binding and cleavage of complementary target RNAs. The
      target-binding domain of one of the ribozymes was fully complementary to a 16
      ribonucleotide stretch on the immobilised substrates, while the other ribozyme
      had a nine-ribonucleotide complementarity. The two ribozymes could readily be
      differentiated with regard to affinity. Cleavage could be measured, using the
      ribozyme with full target complementarity to the cleavable substrate. In
      contrast, the ribozyme with lower affinity lacked cleavage activity. We suggest
      that SPR will be useful for investigations of ribozyme-substrate interactions.

PMID- 10889276
TI  - Quantitative microscopy after fluorescence in situ hybridization - a comparison
      between repeat-depleted and non-depleted DNA probes.
AB  - Complex probes used in fluorescence in situ hybridization (FISH) usually contain
      repetitive DNA sequences. For chromosome painting, in situ suppression of these
      repetitive DNA sequences has been well established. Standard painting protocols
      require large amounts of an unlabeled 'blocking agent', for instance Cot-1 DNA.
      Recently, it has become possible to remove repetitive DNA sequences from library
      probes by means of magnetic purification and affinity PCR. Such a 'repeat
      depleted library probe' was hybridized to the q-arm of chromosome 15 of human
      metaphase spreads and interphase cell nuclei without any preannealing by Cot-1
      DNA. Apart from this, 'standard' FISH conditions were used. After in situ
      hybridization, microscope images were obtained comparable to those achieved with
      the #15q library probe prior to depletion. The images were recorded by a true
      color CCD camera. By digital image analysis using 'line scan' and 'area scan'
      procedures, the painting efficiency expressed in terms of relative fluorescence
      signal intensity was quantitatively evaluated. The painting efficiency using the
      repeat depleted probe of chromosome 15q was compared to the painting efficiency
      after standard FISH. The results indicate that both types of probes are
      compatible to a high FISH efficiency. Using equivalent probe concentrations, no
      significant differences were found for FISH with standard painting probes and
      repeat depleted painting probes.

PMID- 10889277
TI  - A safer and relatively shorter method for Southern blot hybridization analysis.
AB  - The study presented here describes a Southern blot hybridization technique which
      is performed in a shorter time and safer than the classical one. In this study
      DNA was isolated from a small amount of blood sample and the probe for
      hybridization was prepared with (35)S by polymerase chain reaction.

PMID- 10889278
TI  - Discrete analysis of plasma oxalate with alkylamine glass bound sorghum oxalate
      oxidase and horseradish peroxidase.
AB  - We have reported a simple method of determination of plasma oxalate using a Cl(-)
      and NO(3)(-) insensitive oxalate oxidase purified from grain sorghum leaf and
      commercially available peroxidase from horseradish [Pundir et al., Ind. J.
      Biochem. Biophys., 35 (1998) 120-122]. The present report describes the
      immobilization of both the enzymes onto alkylamine glass, their kinetic
      properties and application for discrete analysis of plasma oxalate. In the
      analytic method, H(2)O(2) generated from plasma oxalate by immobilized oxalate
      oxidase is measured colorimetrically at 520 nm by oxidative coupling with 4
      aminophenazone, and phenol catalyzed by immobilized peroxidase. The minimum
      detection limit of the method is 2.5 micromol/l. Analytic recovery of added
      oxalate in plasma was 89. 5+/-4.1% (mean+/-S.D.). The within and between day CV
      for plasma oxalate measurement were <9.37 and <11.0%, respectively. The normal
      range of plasma oxalate as measured by the present method was 3.6 to 5.7
      micromol/l. The method is not only free from interference by plasma Cl(-) and
      NO(3)(-) but also provides the reuse of glass beads and thus reduces the cost of
      analysis for routine.

PMID- 10889279
TI  - An enzymatic assay for myo-inositol in tissue samples.
AB  - An enzymatic assay for myo-inositol (MI) was modified. The method is based on the
      oxidation of MI by NAD(+)-dependent MI dehydrogenase, coupled to reoxidation of
      NADH by iodonitrotetrazolium chloride and diaphorase. The resultant formazan is
      measured spectrophotometrically. In order to remove interference by glucose,
      preliminary phosphorylation of glucose by hexokinase was employed before the
      above reaction. The assay is quantitative for MI in amounts ranging from 1 to 20
      nmol. This method gives a negligible blank, even in the measurement of rat serum.
      The reduced MI content in the sciatic nerve and lens of streptozotocin-induced
      diabetic rats recovered in a dose-dependent manner by treatment with a novel
      potent aldose reductase inhibitor, GP-1447 ?3-[(4,5, 7-trifluorobenzothiazol-2
      yl)methyl]-5-methylphenylacetic acid?.

PMID- 10889280
TI  - Fast, isotope-free methods for the assay of thiamine-binding proteins and for the
      determination of their affinities to thiamine-related compounds.
AB  - A fast, isotope-free method for the determination of parameters for the
      interactions of proteins with thiamine and related compounds was developed. The
      free and bound forms of a ligand (thiamine or a fluorogenic analogue) were
      separated by ultrafiltration using commercially available centrifugal protein
      microconcentrators (Nanosep, Pall Filtron). The free thiamine concentration in
      the filtrate was analysed by (i) a pre-column derivatisation of thiamine to
      thiochrome with the use of alkaline potassium hexacyanoferrate(III) followed by
      reverse-phase HPLC (isocratic, analytical ODS column, 10 mM potassium phosphate,
      pH 7.8, 5% tetrahydrofuran) with fluorometric detection (excitation at 365 nm,
      emission at 430 nm), or (ii) an ion-pair reverse-phase HPLC (isocratic, ODS
      column, 0.08% trifluoroacetic acid-0.08% sodium octanesulfonate-25%
      tetrahydrofuran) with post-column derivatisation and fluorometric detection. The
      'saturation-binding' version (single ligand added in increasing doses to the
      protein samples) of this method allowed the determination of low micromolar
      concentrations of thiamine-binding proteins and of the dissociation constants of
      their complexes with thiamine or fluorogenic thiamine analogues in the range of
      0.3-10 microM. Using the other, 'competitive displacement' version (constant
      amount of thiamine plus increasing doses of a competing ligand), dissociation
      constants at least one order of magnitude higher could successfully be
      determined.

PMID- 10889281
TI  - Isolation of lectins from hemolymph of decapod crustaceans by adsorption on
      formalinized erythrocytes.
AB  - Hemolymph of decapod crustaceans contains lectins of important specificity. An
      isolation procedure, based on adsorption of hemolymph lectins on red blood cells
      (RBC) fixed with formaldehyde, is described. Hemolymph is let to clot for 3 h at
      22-28 degrees C (RT) and for 24 h at 5 degrees C; centrifuged at 13000 g for 30
      min; filtered through 5-microm filters; diluted with an equal volume of 50 mM
      NaCl, 100 mM CaCl(2); supplemented with protease as well as phenoloxidase
      inhibitors; centrifuged at 13000 g for 20 min. Formalinized RBC (FRBC) are mixed
      with diluted hemolymph to a suspension of about 20% v/v FRBC. After incubation
      for 30 min at RT, FRBC are washed five times with 150 mM NaCl, 10 mM CaCl(2). The
      lectins adsorbed on FRBC are desorbed using either 100-500 mM of carbohydrate
      solutions in 0.9% NaCl or 50 mM Tris-HCl buffer, pH 8.0 containing 100 mM NaCl
      and 20 mM entylenediaminetetraacetate (EDTA). The procedure is efficient in
      isolating the hemolymph lectins of the decapods Liocarcinus depurator and Potamon
      potamios.

PMID- 10889282
TI  - The use of magnetite-doped polymeric microspheres in calibrating cell tracking
      velocimetry.
AB  - Continuous magnetic separation, in which there is no accumulation of mass in the
      system, is an inherently dynamic process, requiring advanced knowledge of the
      separable species for optimal instrument operation. By determining cell
      magnetization in a well-defined field, we may predict the cell trajectory
      behavior in the well-characterized field environments of our continuous
      separators. Magnetization is determined by tracking the migration of particles
      with a technique known as cell tracking velocimetry (CTV). The validation of CTV
      requires calibration against an external standard. Furthermore, such a standard,
      devoid of the variations and instabilities of biological systems, is needed to
      reference the method against day-to-day shifts or trends. To this end, a method
      of synthesizing monodisperse, magnetite-doped polymeric microspheres has been
      developed. Five sets of microspheres differing in their content of magnetite, and
      each of approximately 2.7 microm diameter, are investigated. An average gradient
      of 0.18 T/mm induces magnetic microsphere velocities ranging from 0.45 to 420
      microns/s in the CTV device. The velocities enable calculation of the microsphere
      magnetization. Magnetometer measurements permit the determination of
      magnetization at a flux density comparable to that of the CTV magnet's analysis
      region, 1.57 T. A comparison of the results of the CTV and magnetometer
      measurements shows good agreement.

PMID- 10889283
TI  - Do selective serotonin re-uptake inhibitors enhance the efficacy of very brief
      cognitive behavioral therapy for panic disorder? A pilot study.
AB  - Selective serotonin re-uptake inhibitors (SSRIs) and cognitive behavioral
      therapies (CBTs) are both considered as first-line treatments for panic disorder,
      but the advantages of a combined therapy have yet to be definitively
      demonstrated. We evaluated in this pilot study the effects of combining SSRIs
      (vs. a placebo) with a very brief form of cognitive-behavioral therapy provided
      to all participants. Thirty-three subjects with DSM-IV panic disorder, with or
      without agoraphobia, were randomized to receive either paroxetine or a placebo
      with flexible dosing (10-50 mg/day). Medication visits were brief (15 min),
      infrequent (6 in total) and non-directive. An expert cognitive-behavior therapist
      administered one initial 45-min session and one subsequent 30-min session of very
      brief CBT (vbCBT) at weeks 5 and 7, respectively. Sessions were supplemented with
      educational and directive reading materials. Patients in both groups (i.e.
      vbCBT+paroxetine; vbCBT+placebo) improved similarly and substantially on most
      measures during the 10 weeks of acute treatment. At week 10, the proportion of
      panic-free patients was significantly higher in the paroxetine-treated group than
      in the placebo group (80 vs. 25%; P<0.007), as was the proportion of subjects who
      rated themselves as 'very much improved' at week 10 (60 vs. 13%; P<0.017). These
      findings point to the need for additional studies to confirm the effectiveness of
      very brief forms of CBT, and to document the circumstances in which combined
      treatment with an SSRI would be warranted.

PMID- 10889284
TI  - Estrogen affects cognition in women with psychosis.
AB  - Estrogen has been reported to affect aspects of cognition and psychopathology in
      women, both normal and with psychosis. This study aimed to replicate and extend
      this research by investigating the effect of estrogen on cognition over the
      menstrual cycle in a group of normal women and women with psychosis. The sample
      consisted of 31 premenstrual normal control subjects, and 29 women with
      psychosis. Subjects were tested twice, 2 weeks apart on a number of cognitive
      tests. There was no difference in Positive and Negative Symptom Scale scores
      between the follicular and luteal phases of the menstrual cycle. Both groups of
      women performed better on the Revised Mental Rotation Test and Trails A during
      the follicular phase when estrogen levels were low. Contrary to expectation,
      during the luteal phase, when estrogen was high, the control subjects showed no
      significant improvement in performance on verbal articulatory-motor tasks, and
      the women with psychosis performed significantly worse on the Purdue Pegboard.
      The unexpected adverse effect of high levels of estrogen on motor performance in
      the psychotic women was hypothesized to be related to their disease process.

PMID- 10889285
TI  - Clinical utility of the premenstrual assessment form as an instrument auxiliary
      to the diagnosis of premenstrual dysphoric disorder.
AB  - The Premenstrual Assessment Form (PAF) is a retrospective self-report
      questionnaire, yielding classification into syndromal categories and severity
      assessment (unipolar summary scales) of behavioral, psychological and physical
      premenstrual changes. However, the PAF has been criticized due to an overlap of
      its syndromal categories and the unipolar summary scores from symptomatic and
      asymptomatic women. PAF data from women seeking treatment for premenstrual
      symptoms and meeting a provisional diagnosis of premenstrual dysphoric disorder
      (PMDD; n=30) were compared to a control group (n=16). Results showed that 97% of
      the symptomatic group met the PAF depressive premenstrual syndrome criteria vs.
      only 12% of the control subjects (chi(2)=29.9, P<0.001). The symptomatic group
      also reported more severe premenstrual symptoms in all unipolar scales than the
      control subjects. Sixteen symptomatic women completed two menstrual cycles of
      prospective daily ratings, and half of them had their provisional diagnosis of
      PMDD confirmed. There were no significant differences in the scores of the PAF
      unipolar summary scales between the subgroups with or without the diagnosis
      confirmation. Most of the PAF scales displayed high sensitivity, but low
      specificity. These findings suggest that the PAF can be useful to differentiate
      clinical population and control samples, but it does not provide information to
      make a more definite diagnosis of PMDD.

PMID- 10889286
TI  - Evaluation of expressed emotion (EE) status in mood disorders in japan: inter
      rater reliability and characteristics of EE.
AB  - The reliability of expressed emotion (EE) ratings by the Camberwell Family
      Interview (CFI) and characteristics of EE were evaluated in families of patients
      with mood disorders in Japan. The subjects were 27 patients with mood disorders
      and 31 members of their families. The CFI was carried out with the family
      members. EE was rated by two raters independently, and the inter-rater
      reliability was evaluated according to Spearman's correlation coefficient by
      ranks and the kappa-value. The distribution of subscales of EE in these subjects
      was compared with that in families of patients with schizophrenia in Japan and
      families of patients with mood disorders abroad. Concerning critical comments
      (CC), hostility (H), and emotional over-involvement (EOI), which are important
      for EE rating, Spearman's correlation coefficient and the kappa-values were 0.4
      0.8, and the reliability of EE ratings in mood disorders was not high. The
      proportion of positive agreement was particularly low in H and EOI. CCs were
      fewer in families of Japanese patients with mood disorders than in those with
      schizophrenia or families of American or European patients with mood disorders.
      Re-evaluation of the inter-rater reliability of EE ratings in mood disorders is
      needed. Expressed emotion was more suppressed in families of patients with mood
      disorders than in those of patients with schizophrenia. Expressed emotion was
      also more reserved in the Japanese subjects than in their Western counterparts.

PMID- 10889287
TI  - The low prevalence of high levels of expressed emotion in Bali.
AB  - The present study contrasts the expressed emotion (EE) status in family members
      of schizophrenic patients between Bali (Indonesia) and Tokyo (Japan), the former
      being a non-industrialized society and the latter an industrialized society in
      Asia. The EE ratings of each key relative for 62 consecutively hospitalized
      schizophrenic patients at the Bangli State Mental Hospital (Bali) and 33
      consecutively admitted schizophrenics at Komagino Hospital (Tokyo) were obtained
      using the Five Minute Speech Sample (FMSS) method. A significantly lower
      prevalence of high EE (12.9%) was observed in Bali compared with Tokyo (36.4%)
      (P<0.01). This result may explain the better social adjustment of schizophrenics
      in Bali. In addition, in Bali, to clarify the EE effect in this non
      industrialized society, we examined the relationship between each key relative's
      EE and the patient's psychotic symptoms at admission, as assessed by the Brief
      Psychiatric Rating Scale (BPRS) and the Scales for the Assessment of Negative
      Symptoms (SANS). Moreover, the association between each family member's EE and a
      patient's rate of re-admission over the 1-year period following discharge was
      evaluated. The EE value was significantly related to the anxious-depression
      factor score in the BPRS, but not to either of the other factor scores in the
      BPRS or SANS subscales. Furthermore, EE status was not a reliable predictor of
      patient re-admission over the 1-year period following discharge in Bali.

PMID- 10889288
TI  - Multi-impulsivity of Japanese patients with eating disorders: primary and
      secondary impulsivity.
AB  - Several studies have noted that multi-impulsive bulimia nervosa tends to be
      refractory to treatment. However, it is not known whether these impulsivities are
      an expression of more fundamental psychopathology or simply the consequence of
      chaotic eating behaviors. Studies of the temporal relationship between the onset
      of eating disorder and the occurrence of impulsive behaviors will facilitate a
      better understanding of these issues. Subjects consisted of 60 patients with
      anorexia nervosa restricting type (AN-R), 62 patients with anorexia nervosa binge
      eating/purging type (AN-BP), 114 patients with bulimia nervosa purging type (BN)
      and 66 control subjects. Impulsive behaviors and childhood traumatic experiences
      were assessed by self-report questionnaire. Multi-impulsivity (defined by at
      least three of the following: heavy regular alcohol drinking; suicide attempt;
      self-mutilation; repeated shoplifting of items other than food; sexual
      relationships with persons not well known to the subject) was found in 2% of AN
      R, 11% of AN-BP, 18% of BN and 2% of control subjects. Eighty percent of BN
      patients with multi-impulsivity had a history of suicide attempts or self
      mutilation history prior to the onset of bulimia nervosa. In BN patients, there
      tended to be a relationship between childhood parental loss or borderline
      personality disorder and multi-impulsivity. In conclusion, primary impulsivity
      (chronological prior occurrence of impulsive behaviors) does exist even in a very
      different culture, although the number of patients of this type is very limited.

PMID- 10889289
TI  - Mood effects of repetitive transcranial magnetic stimulation of left prefrontal
      cortex in healthy volunteers.
AB  - This study investigated the effect of high-frequency repetitive transcranial
      magnetic stimulation (HF-rTMS) of the left prefrontal cortex (LPFC) on mood in a
      sham-controlled crossover design. Twenty-five healthy male subjects received HF
      rTMS of the LPFC in real and sham conditions. Forty trains (frequency 20 Hz,
      stimulation intensity 100% of individual motor threshold, train duration 2 s,
      intertrain interval 28 s) were applied in each session. Mood change from baseline
      was measured with five visual analog scales (VAS) for sadness, anxiety,
      happiness, tiredness and pain/discomfort. We were unable to demonstrate
      significant mood changes from baseline on visual analog scales after either sham
      or real stimulation of LPFC. There is insufficient evidence to support the
      general conclusion that HF-rTMS of LPFC has mood effects in healthy volunteers.
      Future studies should be sham-controlled, have larger sample sizes, and strictly
      stimulate one single region per session in order to exclude interaction effects
      with the previous stimulation.

PMID- 10889290
TI  - A CAG trinucleotide repeat expansion and familial schizophrenia.
AB  - Studies which showed anticipation in families with schizophrenia suggested that a
      trinucleotide repeat expansion mechanism may be involved in the pathogenesis of
      familial schizophrenia. Furthermore, some studies involving the repeat expansion
      detection (RED) method showed the median length of CAG repeats to be longer in
      probands with schizophrenia than that in control subjects. We screened for a
      possible expanded CAG repeat by means of the direct identification of repeat
      expansion and cloning technique in 23 subjects (affected, 14; unaffected, 9) from
      six families with schizophrenia which showed anticipation. The polymorphism of a
      long and unstable CAG/CTG trinucleotide repeat, Dir1, was studied by PCR. No
      unusual expanded CAG/CTG trinucleotide repeat was detected in the subjects with
      familial schizophrenia. There was no significant difference between the affected
      and unaffected subjects in the allele frequency of Dir1. Our results suggest that
      a CAG expansion is not the mechanism underlying familial schizophrenia.

PMID- 10889291
TI  - No effect of light on basal glucagon levels in winter seasonal depressives and
      comparison subjects.
AB  - We explored the effect of light therapy upon basal fasting plasma glucagon in 15
      patients with winter depression vs. 15 comparison subjects before and after at
      least 1 week of light treatment. No differences were seen between groups or
      conditions. There was no correlation between glucagon change and antidepressant
      response.

PMID- 10889292
TI  - Decreases in dilated pupil size in depressed patients with age may reflect
      adrenergic changes.
AB  - Some studies have suggested that noradrenergic activity may decrease with age in
      depressed patients. Pupil size is regulated by a balance between norepinephrine
      and acetylcholine. The present study compares pupil size in 10 unmedicated
      patients with unipolar depression (296. 3) and in 16 normal controls. Pupil size
      after dilation with tropicamide, a cholinergic antagonist, was inversely related
      to age in the patients (r=-0.87), but did not diminish with age in controls. The
      results suggest that pupil size may provide an index of diminished noradrenergic
      function with age in patients with major depression.

PMID- 10889293
TI  - Distribution of platelet 5-HT(2A) receptor densities in suicidal and non-suicidal
      depressives and control subjects.
AB  - The frequency distribution of platelet 5-HT(2A) receptor densities (measured as
      [3H]LSD B(max)) was analysed in 60 patients with major depression and 40 matched
      control subjects to determine whether the observed receptor densities come from a
      single distribution or whether there are more distributions that are represented
      differently in control subjects and in diagnostic subgroups of non-suicidal and
      suicidal patients. The distribution of B(max) values in all subjects was tested
      by using the NOCOM program. The analysis has shown a best fit for a trimodal
      distribution of values (low, intermediate and high binding). There were
      significant differences in average probabilities of control subjects and patients
      from the two diagnostic subgroups belonging to any of the three distributions. In
      the control and non-suicidal groups, a significantly higher (P=0.003) proportion
      of individuals had a probability of belonging to a low binding distribution. In
      contrast, the probability of belonging to the high distribution was significantly
      greater (P=0.007) in the suicidal group of patients than in the non-suicidal
      group or in control subjects. In all three groups, the proportion of cases in
      each distribution fit those expected under the Hardy-Weinberg equilibrium. The
      results support the notion that high 5-HT(2A) receptor density is a marker of
      suicidality, possibly genetically determined.

PMID- 10889294
TI  - Prolonged QT interval in acute psychotic patients.
AB  - Some recent clinical studies indicate that hypokalemia is characteristic for
      acute psychotic patients at the time of emergency admission. As hypokalemia is
      one of the major causes for prolonged QT interval, it was hypothesized that acute
      psychotic patients could show prolonged QT interval. Sixty-seven drug-free, acute
      psychotic patients were evaluated for corrected QT (QTc) interval, as well as
      demographic and clinical characteristics at the time of emergency admission. The
      mean QTc interval of psychiatric emergency patients was prolonged, and the mean
      QTc interval of psychiatric emergency patients was longer than that of
      psychiatric outpatients (t=5.20, P<0.0001). Age- or gender-related difference,
      circadian fluctuation of QT interval, medication, concomitant disease, obesity,
      and serum electrolytes except potassium were not major causes. There was a
      significant negative correlation as evidenced by a coefficient of correlation of 
      0.28 (P<0.05). As psychiatric emergency patients often receive parenteral
      antipsychotics, which may have adverse effects on prolonged QT interval, paying
      attention to QT interval might have some clinical significance on emergency
      admission.

PMID- 10889295
TI  - Detection of protein binding to a glucocorticoid response element-like sequence
      in a chicken major histocompatibility complex class II promoter.
AB  - The glucocorticoid response element in gene promoters mediates regulation of gene
      expression by glucocorticoids. The major histocompatibility (MHC) class II genes,
      crucial for immunoresponsiveness, are among those modulated by glucocorticoids. A
      GRE-like sequence has been located in the promoter of a chicken MHC class II
      promoter. DNase footprinting revealed protein binding by the GRE-like sequence
      when nuclear extract from chicken T or B cell lines were used. Gel shift assays
      detected multiple binding activities in the lymphocyte cell lines, but little
      binding in the macrophage cell line. Relative band intensity differed among the
      lymphocyte cell lines. By using a mutant GRE oligonucleotide, most of the binding
      activities were demonstrated to be specific to the GRE. This study suggests a
      role of the GRE-like sequence in regulating chicken MHC class II genes and
      provides further evidence for the previously reported influence of
      glucocorticoids on chicken MHC class II expression which may be the molecular
      basis of glucocorticoid immunomodulation.

PMID- 10889296
TI  - Immunological and inflammatory characterisation of three canine cell lines: K1,
      K6 and DH82.
AB  - Three canine cell lines, K1, K6 and DH82, derived from canine malignant
      neoplasms, were characterised. They were examined for expression of surface
      antigens, cytokines, neuropeptide receptors, matrix metalloproteinases (MMPs) and
      tissue inhibitors of metalloproteinases (TIMPs). The growth characteristics of
      the cell lines were established and bioassays used to detect production of TNF
      alpha, IL-1 and IL-6. In the DH82 cell line, production of TNF-alpha and IL-6 was
      readily detected. Neither K1 or K6 cell lines produced any measurable amounts of
      TNF-alpha, IL-1 or IL-6. At a molecular level, using reverse transcription
      polymerase chain reaction (RT-PCR) to detect specific mRNA, the DH82 cell line
      expressed TNF-alpha, IL-1 and IL-6, whereas the K1 and K6 cell lines expressed
      TNF-alpha. Canine IL-5, IL-8 and IL-10 mRNA were detected in the DH82 cell line
      but only IL-5 and IL-8 mRNA were detected in the K1 and K6 cell lines. Gelatin
      zymography was used for the detection of MMP-2 and MMP-9 and all three cell lines
      produced MMP-2 but only the DH82 cell line produced MMP-9. Reverse zymography was
      used to detect TIMP-1 and TIMP-2 and all three cell lines produced both proteins.
      The presence of these MMPs and TIMPs was confirmed at a molecular level using RT
      PCR. Canine MMP-14 mRNA was detected in all three cell lines. For this
      investigation several genes for canine inflammatory molecules were cloned and
      sequenced for molecular detection; these included IL-1, IL-6, IL-8, TNF-alpha,
      MMP-9, MMP-14, TIMP-1, TIMP-2 and beta-actin. Of all the cell surface antigens
      tested, only CD14 was expressed on the DH82 cell line although CD5 and CD45 was
      partially expressed. The K1 and K6 cell lines were negative for all of the CD
      markers tested. K1 and K6 were negative for Neurokinin 1 receptor (NK1-R) but
      positive for Calcitonin gene related peptide receptor type 1 (CGRP-1R) and
      Calcitonin gene related peptide receptor component protein (CGRP-RCP). The DH82
      cell line expressed neither NK1-R or CGRP-1R; however, it did express CGRP-RCP.
      Generally the DH82 cell line exhibited considerable similarity to canine
      monocytes, but all three cell lines will be useful as standards and for the
      purification of various immunological and inflammatory mediators in the dog.

PMID- 10889297
TI  - Characterization of the diffuse mucosal associated lymphoid tissue of feline
      small intestine.
AB  - Characterization of the feline intestinal mucosal associated lymphoid tissue
      (MALT) will facilitate investigation of intestinal disease in the cat and promote
      the cat as an animal model for a range of human diseases which involve the
      intestinal lymphoid tissue. This includes inflammatory bowel disease, viral and
      non-viral associated intestinal lymphomas and immunodeficiency associated
      syndromes. Morphologic and phenotypic characterization of the normal small
      intestinal diffuse MALT in 22 SPF cats was performed using flow cytometry and
      cytology on isolated intestinal leukocytes from the intra-epithelial and lamina
      proprial compartments, as well as immunohistology on tissues from the feline
      duodenum, jejunum and ileum. The intra-epithelial compartment (IEC) was dominated
      by lymphocytes (>85%) which frequently contained intracytoplasmic granules. The
      most striking findings in the IEC were the elevated percentages of CD8 alpha+
      lymphocytes (40%), presumed to express CD8 alpha alpha chains, and CD4-/CD8-
      (double negative) lymphocytes (44%), and the consistent presence of a minor
      subpopulation of CD3+/CD11d+ IELs (6%). Small percentages of CD4+ lymphocytes
      (10%) were observed such that the IEL CD4:CD8 ratio (0.25) was low. The LPC also
      contained a majority of T cells and few plasma cells. However, this compartment
      had reduced percentages of CD8 alpha+ lymphocytes (28%) and increased percentages
      of CD4+ lymphocytes (27%) relative to the IEC. However, the LPL CD4:CD8 ratio
      (1.0) remained low compared with the ratio in peripheral blood. In feline MALT,
      MHC class II expression was lower than in other peripheral lymphoid compartments.
      The results of this study provide important reference values for future
      investigations involving feline intestinal lymphocytes and demonstrates that the
      leukocyte distribution and phenotypic characteristics of the feline diffuse MALT
      appear largely similar to the murine, rat and human counterparts.

PMID- 10889298
TI  - Cyclic CD8+ lymphopenia in dogs experimentally infected with Bartonella vinsonii
      subsp. berkhoffii.
AB  - Until recently, it was presumed that Bartonella vinsonii only infected voles, a
      species of North American rodents. In April of 1993, however, our laboratory
      isolated a novel subspecies of B. vinsonii (B. vinsonii subsp. berkhoffii) from
      the blood of a dog diagnosed with vegetative valvular endocarditis. Subsequently,
      based on a seroepidemiologic survey of dogs from North Carolina and Virginia
      presenting for a variety of medical problems, we found evidence supporting a
      potentially important association between B. vinsonii and Ehrlichia canis co
      infection in dogs. In the following study, eight dogs were infected with B.
      vinsonii: four specific pathogen free dogs and four dogs that had previously been
      infected with E. canis. Flow cytometric analysis of peripheral blood lymphocytes
      revealed a cyclic elevation of the CD4/CD8 T-cell ratio that correlated with
      cyclic CD8+ lymphopenia in all dogs infected with B. vinsonii, regardless of
      prior exposure to E. canis.

PMID- 10889299
TI  - Partial sequences of feline and caprine immunoglobulin epsilon heavy chain cDNA
      and comparative binding studies of recombinant IgE fragment-specific antibodies
      across different species.
AB  - Parts of the feline and caprine IgE epsilon heavy chain cDNA (third and fourth
      constant domains, IgEf3/4) were cloned, sequenced, and expressed to raise
      antibodies (Abs). The DNA and derived protein sequences of the feline recombinant
      IgEf (rIgEf) shared high homology with the analogous canine parts (81% at the
      nucleotide and 71% at the protein levels) and the caprine with the ovine ones
      (95%/84%), respectively. The polyclonal Abs raised in chickens against the feline
      and caprine rIgEf3/4 were subjected to a comparative binding study utilizing an
      ELISA including rIgEf and specific Abs to these rIgEf from dog and horse (rIgEf2
      and rIgEf3/4) and sheep (rIgEf3/4). All but the ovine-specific rIgEf3/4 Ab were
      polyclonal, which had been raised in chickens, and bound to most applied rIgEf;
      the ovine-specific monoclonal mouse Ab recognized only in addition to ovine
      rIgEf3/4 the closely related caprine rIgEf3/4. Significant, positive correlations
      were detected between binding reactions of the polyclonal Abs in ELISA and
      percentage protein sequence homology (p<0.01). Thus, the newly described feline
      and caprine IgE nucleotide sequences and corresponding Abs represent useful tools
      for further species-specific and comparative allergy and disease-associated
      research.

PMID- 10889300
TI  - Equid herpesvirus 1: platelets and alveolar macrophages are potential sources of
      activated TGF-B1 in the horse.
AB  - Cell mediated responses to Equid herpesvirus 1 (EHV-1) are of short duration in
      vivo and require considerable expansion to be detected in vitro. Raised serum
      levels of active transforming growth factor B (TGF-B1) have been shown to depress
      proliferative T cell responses in experimental infections with EHV-1 in ponies.
      The present work indicates that latent transforming growth factor B (TGF-B1) is
      present in circulating platelets, lymph node, bronchial epithelium and alveolar
      macrophages. Activation of platelets in vitro by thrombin resulted in the release
      of latent TGF-B1 from platelets, with a pg level of conversion to active TGF-B1,
      but virus alone did not activate TGF-B1. Exposure of circulating leucocytes to
      EHV-1 in vivo or in vitro does not result in detection of active TGF-B1 above
      residual levels that could be attributed to activation of platelets by
      manipulation. However, alveolar macrophages obtained by lavage at autopsy yield
      both latent and active TGF-B1 in ng quantities. Bronchial epithelium, and
      mesenteric lymph node leucocytes had equivalent levels of latent TGF-B1, but
      horses varied as to whether these tissues were a source of activated TGF-B1 and
      as to whether EHV-1 activated TGF-B1.

PMID- 10889301
TI  - Non-specific responses of turbot (Scophthalmus maximus L.) adherent cells to
      microsporidian spores.
AB  - We investigated non-specific responses of turbot spleen- and pronephros-resident
      adherent cells to spores of fish microsporidians, and the effects of the
      glucocorticoid dexamethasone (DX) on these responses. On average, 65% of adherent
      cells from the spleen and pronephros showed esterase activity (as characteristic
      of macrophages); 32% showed peroxidase activity (as characteristic of
      neutrophils), and 19% of peroxidase-positive cells were capable of phagocytosing
      microsporidian spores. A significantly higher proportion of adherent cells showed
      phagocytic activity when viable spores were the target than when non-viable
      spores were the target. Microsporidian spores stimulated adherent cells to
      produce reactive oxygen and nitrogen intermediates (ROIs and RNIs), though less
      effectively than the other stimulants tested. Adherent cells exposed to viable
      spores produced significantly less intracellular superoxide than adherent cells
      exposed to non-viable spores. Daily injection of fish with DX over 6 days
      significantly inhibited both phagocytosis of microsporidian spores and spore
      induced ROI production, and similar effects were observed when adherent cells
      were exposed to DX in vitro.

PMID- 10889302
TI  - Stem cell factor enhances IgE-mediated histamine and TNF-alpha release from
      dispersed canine cutaneous mast cells.
AB  - Stem cell factor (SCF), the c-kit receptor ligand, plays a critical role in mast
      cell (MC) development and differentiation. In addition, SCF has recently been
      found to both modulate and induce MC activation. To investigate the effect of SCF
      on canine cutaneous MC function, we have characterized the ability of SCF to
      modulate the release by mature canine MC of preformed (histamine) and newly
      generated (TNF-alpha) mediators. Mature MC were isolated from skin and cultured
      in the absence or presence of exogenous SCF (6 ng/ml) for up to 5 days and then
      challenged with anti-IgE (1 microg/ml) alone for 30 min or with a combination of
      SCF (50 ng/ml) and anti-IgE. SCF alone failed to trigger either histamine or TNF
      alpha release at any time. However, we observed that SCF used as a co-stimulus
      significantly potentiated histamine and TNF-alpha release in canine MC activated
      through Fc epsilon RI regardless of whether or not SCF was added to the medium
      during culturing. Thus, the mean histamine release (%) and TNF-alpha production
      (pg/ml) were found to be significantly higher if cells were maintained in culture
      in SCF-supplemented medium compared with cells cultured in the absence of
      exogenous SCF. We also observed that MC responsiveness to immunological
      stimulation increased with culture time, the percentage of histamine released
      being higher in cells cultured for at least 3 days when compared to freshly
      isolated MC. Taken together these findings suggest that canine skin MC
      releasability can be enhanced independently either through prolonged incubation
      with SCF and/or through anti-IgE and SCF co-stimulation.

PMID- 10889303
TI  - Cellular profiles in the abomasal mucosa and lymph node during primary infection
      with Haemonchus contortus in sheep.
AB  - Cellular changes in the abomasal tissue and draining abomasal lymph nodes were
      examined after primary infection of lambs with Haemonchus contortus for 3, 5 or
      27-36 days. Infection with H. contortus larvae resulted in a rapid and selective
      increase in the percentage of CD4(+) T-cells in the abomasal lymph node at 3 days
      post-infection (PI). By 5 days PI, the lymph node weight had increased two-fold;
      however, the percentage of lymphocyte populations in the abomasal lymph node
      resembled that seen in uninfected sheep. Lymph node weights remained at increased
      levels in the adult nematode infected sheep and down-regulation of B-cell surface
      markers (sIg and MHC Class II) was apparent in this group. Significant increases
      in the percentage of CD4(+) T-cells co-expressing MHC Class II, but not CD25,
      were observed in the larval infected groups except in adult nematode infected
      sheep. Increased numbers of eosinophils, CD4(+), gamma delta(+) T-cells and B
      cells were found in the abomasal tissue by 5 days PI, but no further increases in
      these cell populations were observed in the adult nematode infected group. In
      contrast, the level of both lamina propria and intraepithelial mast cells
      observed in the abomasal mucosa was highest in the sheep carrying an adult
      nematode burden. These findings indicate that sheep are able to generate an early
      immune response to infection with H. contortus larvae, characterised by the
      activation of CD4 T-cells and B-cells in the draining lymph nodes and recruitment
      of eosinophils, CD4(+) and gamma delta-TCR,WC1(+) T-cells and B-cells in larval
      infected tissues. However, these changes do not seem to be maintained during
      infection with the adult parasite where increases in mast cell numbers dominate
      the local response, indicating that different parasite stages may induce distinct
      and possibly counteractive immune responses.

PMID- 10889304
TI  - B-cell function in canine X-linked severe combined immunodeficiency.
AB  - Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in
      the common gamma (gammac) subunit of the IL-2, IL-4, IL-7, IL-9 and IL-15
      receptors and has a similar clinical phenotype to human XSCID. We have previously
      shown that the block in T-cell development is more profound in XSCID dogs than in
      genetically engineered gamma c-deficient mice. In this study we evaluated the B
      cell function in XSCID dogs. In contrast to the marked decrease in peripheral B
      cells in gamma c-deficient mice, XSCID dogs have increased proportions and
      numbers of peripheral B-cells as observed in XSCID boys. Canine XSCID B-cells do
      not proliferate following stimulation with the T-cell-dependent B-cell mitogen,
      pokeweed mitogen (PWM); however, they proliferate normally in response to the T
      cell-independent B-cell mitogen, formalin-fixed, heat-killed Staphylococcus
      aureus. Canine XSCID B-cells are capable of producing IgM but are incapable of
      normal class-switching to IgG antibody production as demonstrated by in vitro
      stimulation with PWM and immunization with the T-cell-dependent antigen,
      bacteriophage PhiX174. Similar results have been reported for XSCID boys. Thus,
      it appears that gamma c-dependent cytokines have differing roles in human and
      canine B-cell development than in the mouse making the XSCID dog a valuable model
      for studying the role of these cytokines in B-cell development and function.

PMID- 10889305
TI  - In vitro IgE but not IgG production of canine peripheral blood B cells is
      inhibited by CD40 ligation.
AB  - The aim of this study was to investigate in vitro IgE induction in peripheral
      canine B cells. CD21(+) B cells were purified from the peripheral blood of beagle
      dogs by positive selection via magnetic separation to a purity of >/=95%.
      Subsequently, proliferation, and IgG and IgE production of canine B cells were
      investigated after stimulation with human recombinant Interleukin-4 (hrIL-4) and
      human recombinant Interleukin-2 (hrIL-2) in the presence or absence of CD40L-CD8
      fusion protein (CD40L) of mouse origin. We could demonstrate that canine B cells
      react on hrIL-2 alone by proliferation and IgG production but not by IgE
      secretion, whereas activation with hrIL-4 induced proliferation and mainly IgE
      production. Together, both cytokines synergistically increased B cell
      proliferation as well as IgG and IgE production. We could also show that mouse
      CD40L induces proliferation of dog B cells, which is further enhanced by addition
      of hrIL-4. Unexpectedly, CD40L led to a dramatic decrease in the IL-4 mediated
      IgE secretion (82% inhibition on an average). In contrast, IgG production was not
      affected significantly by CD40L. The same effects of CD40L were observed when B
      cells were stimulated by a combination of IL-2 and IL-4 and this inhibition could
      not be abrogated by increasing the amounts of IL-4. In summary, activation of
      canine B cells from peripheral blood by hrIL-4 in the presence or absence of hrIL
      2 led to marked IgE production that is strongly and in a dose-dependent manner
      inhibited by CD40L. Stimulation of IgG production is not influenced by CD40L.

PMID- 10889307
TI  - Corrigendum to "A DNA vaccine coding for glycoprotein B of pseudorabies virus
      induces cell-mediated immunity in pigs and reduces virus excretion early after
      infection"

PMID- 10889306
TI  - Molecular cloning and identification of full-length cDNA encoding high affinity
      Fc receptor for bovine IgG (Fc gamma RI).
AB  - The receptor I for the Fc region of immunoglobulin G (Fc gamma RI) is a member of
      the Ig superfamily with a high affinity, and it mediates antibody-dependent
      cellular cytotoxicity and immune complex clearance. In this study, a cDNA
      encoding the bovine Fc gamma RI was cloned. The full-length cDNA sequence is 1050
      bp long with a short 5'- and long 3'-untranslated end regions, which codes for
      349 amino acids and contains a signal peptide, an extracellular region with three
      Ig-like domains, and transmembrane and intracytoplasmic domains. Five potential N
      linked glycosylation sites are recognized in this sequence. Compared with the
      sequences of human and mouse Fc gamma RI, the homologies of nucleotide sequences
      are 80 and 69% and homologies of deduced amino acid sequences are 66 and 55%,
      respectively. It is shown that the sequences of the monomeric IgG binding domain
      in these three species of Fc gamma RI are highly conserved.

PMID- 10889308
TI  - Rapid detection of low levels of Listeria in foods and next-day confirmation of
      L. monocytogenes.
AB  - Outbreaks of foodborne listeriosis caused by Listeria monocytogenes in recent
      years, and the high mortality rate associated with listeriosis, have raised the
      need for reliable and rapid detection of the pathogen. A simple, automated method
      was developed for the detection of Listeria organisms in foods. It consists of a
      6-h pre-enrichment step followed by overnight incubation in selective broth at 35
      degrees C. Changes in light transmittance in the selective broth are registered
      continuously by an optical sensor of the BioSys instrument (MicroSys, Ann Arbor,
      MI), and recorded in the computer. Esculin hydrolysis by listeriae results in
      black coloration of the media that causes a sharp drop in light transmittance,
      whereas negative samples remain colorless. Confirmation of L. monocytogenes is
      carried out only on esculin-positive samples and is completed within 6 h.
      Detection of 10-50 cells of Listeria inoculated into 25 g of food was confirmed
      in shell eggs, milk and ground beef. Naturally contaminated raw and ready-to-eat
      foods were further screened to validate the procedure.

PMID- 10889309
TI  - Direct identification of pure Penicillium species using image analysis.
AB  - This paper presents a method for direct identification of fungal species solely
      by means of digital image analysis of colonies as seen after growth on a standard
      medium. The method described is completely automated and hence objective once
      digital images of the reference fungi have been established. Using a digital
      image it is possible to extract precise information from the surface of the
      fungal colony. This includes color distribution, colony dimensions and texture
      measurements. For fungal identification, this is normally done by visual
      observation that often results in a very subjective data recording. Isolates of
      nine different species of the genus Penicillium have been selected for the
      purpose. After incubation for 7 days, the fungal colonies are digitized using a
      very accurate digital camera. Prior to the image analysis each image is corrected
      for self-illumination, thereby gaining a set of directly corresponding images
      with respect to illumination. A Windows application has been developed to locate
      the position and size of up to three colonies in the digitized image. Using the
      estimated positions and sizes of the colonies, a number of relevant features can
      be extracted for further analysis. The method used to determine the position of
      the colonies will be covered as well as the feature selection. The texture
      measurements of colonies of the nine species were analyzed and a clustering of
      the data into the correct species was confirmed. This indicates that it is indeed
      possible to identify a given colony merely by macromorphological features. A
      classifier (in the normal distribution) based on measurements of 151 colonies
      incubated on yeast extract sucrose agar (YES) was used to discriminate between
      the species. This resulted in a correct classification rate of 100% when used on
      the training set and 96% using cross-validation. The same methods applied to 194
      colonies incubated on Czapek yeast extract agar (CYA) resulted in a correct
      classification rate of 98% on the training set and 71% using cross-validation.

PMID- 10889310
TI  - Microanalysis of antimicrobial properties of human fluids.
AB  - Host defense responses of animals and plants to pathogenic microbes are mediated
      in part by the release of antimicrobial substances into tissue fluids.
      Exploration of the antimicrobial properties of tissue fluids is often limited by
      their small quantity. We have developed assays of antimicrobial activity that
      require only 1 microl of fluid. Using normal nasal secretions as a model mucosal
      fluid we demonstrated that the kinetics of the 1 microl colony-forming unit (CFU)
      assays were equivalent to the larger CFU assays. The handling of viscous mucin
      containing fluids was facilitated by pretreatment with N-acetylcysteine (NAC), a
      treatment that did not alter the performance of the assay. This low-volume assay
      will facilitate studies of the antimicrobial properties of scarce biological
      fluids.

PMID- 10889311
TI  - A colony lift immunoassay for the specific identification and quantification of
      Listeria monocytogenes.
AB  - A colony lift immunoassay (CLI) has been developed to detect Listeria
      monocytogenes after the organisms have been cultured on filter membranes or agar
      plates. Polyvinylidene fluoride membranes (PVDF) (Millipore, Bedford, MA), used
      in the CLI, were prewet with methanol and used to imprint colonies that were
      grown on the filter or agar plates. A positive control was applied to the edge of
      each membrane. The imprinted membranes were subsequently air dried, peroxidase
      neutralized, blocked, and reacted for 20 min with a 2-microg/ml unconjugated Mab
      EM-7G1 solution. The membranes were washed briefly and reacted for 30 min with a
      1:2000 dilution of a commercially prepared peroxidase-labeled goat anti-mouse
      secondary antibody (Kirkegaard and Perry Laboratories (KPL), Gaithersburg, MD).
      After a second wash step, the membranes were exposed to a 3,3',5, 5'
      tetramethylbenzidine membrane substrate (KPL), rinsed in deionized water, and
      allowed to dry. Colonies of L. monocytogenes were identified by a blue color
      reaction on the membrane, which could be used to reference the colonies either on
      the filter membranes or agar plates. The CLI was tested against a wide range of
      Listeria species as well as several non-Listeria species and was shown to have a
      high degree of sensitivity (96%) and specificity (90%). We have shown that it is
      useful as a simple and rapid method to detect and identify L. monocytogenes.

PMID- 10889312
TI  - Heteroduplex mobility assay as a tool for predicting phylogenetic affiliation of
      environmental ribosomal RNA clones.
AB  - Heteroduplex mobility assay (HMA) of partial 16S rRNA gene fragments was tested
      as a tool for predicting bacterial phylogenetic relationships. Approximately 400
      bp fragments were amplified from a selection of cloned environmental DNAs
      representing a range of sequence identities and phylogenetic relationships.
      Heteroduplexes between pairs of sequences were formed by mixing equal amounts of
      PCR products, denaturing and annealing. Annealed mixes were separated on 8%
      polyacrylamide gels and silver stained. Heteroduplexes were readily distinguished
      from reannealed homoduplex and unannealed fragments in all sequences where
      percentage identity was less than 95%. The heteroduplexes showed retarded
      electrophoretic migration with respect to homoduplexes. The relative retardation
      was strongly correlated to the percentage sequence identity between the two
      strands. The HMA is a useful tool for screening environmental clone libraries to
      systematically select clones representative of the phylogenetic diversity within
      the sample, or to selectively retrieve members of a particular phylogenetic group
      for more detailed study.

PMID- 10889313
TI  - Silver stained polyacrylamide gels and fluorescence-based automated capillary
      electrophoresis for detection of amplified fragment length polymorphism patterns
      obtained from white-rot fungi in the genus Trametes.
AB  - Silver stained denaturing polyacrylamide gels (PAGEs) and fluorescent denaturing
      automated capillary electrophoresis (CE) were used to detect amplified fragment
      length polymorphism (AFLP) patterns obtained from white-rot fungi belonging to
      the genus Trametes. AFLP fingerprinting detected by the fluorescence-based method
      as well as by silver staining showed a high discriminatory power in
      differentiating nine strains of Trametes ochracea, nine strains of Trametes
      hirsuta and ten isolates of Trametes versicolor. UPGMA dendrograms derived from
      fluorescently labelled and silver stained AFLP patterns were similar, but a few
      differences were detected especially in the clustering of T. ochracea and T.
      hirsuta strains. Compared to silver-stained AFLP, detection of fluorescent AFLP
      was fast, reliable and easy to perform and it facilitated surveying with a
      computerized analysis system. Fluorescent CE seems to be well suited for studying
      similarity between Trametes species.

PMID- 10889314
TI  - Methods to evaluate nodulation competitiveness between Sinorhizobium meliloti
      strains using melanin production as a marker.
AB  - Three methods to evaluate the relative ability of different strains of
      Sinorhizobium meliloti to occupy nodules formed on alfalfa after co-inoculation
      were compare in this study. Results obtained using the three methods of
      evaluation together, provided insight into the relative nodulation
      competitiveness between two given sinorhizobial strains. A simple visual
      phenotypic marker, i.e., melanin production was used to distinguish individual
      strains in a given assay. As such, melanin producing strains were compared with
      melanin non-producing strains throughout this study. Method 1 required the use of
      an ELISA plate, took 35 min for the analysis of 40 nodules, and allowed strain
      identification by melanin production 2 days after nodule harvest. Method 2
      required 3 h for the analysis of 40 nodules, used an ELISA plate, growth of
      bacteria on Petri dishes, and melanin production was analysed after 48 h of cell
      culture. Finally, method 3 involved the whole nodulated plant root, required less
      material than the above methods, and results were obtained after 24 h. Only
      method 2 was useful in determining if both a melanin producing strain and a
      melanin non-producing strain had occupied an individual nodule. Each of the three
      methods represented a rapid way of studying strain competition for field studies,
      using a natural trait as a marker.

PMID- 10889315
TI  - NO-Donors, part 3: nitrooxyacylated thiosalicylates and salicylates - synthesis
      and biological activities(#).
AB  - Organic nitrates release nitric oxide when incubated with thiosalicylic acid. S
      Nitrooxyacylated esters and amides of thiosalicylic acid, together with the
      corresponding salicylates, were synthesized in order to perform a first in vitro
      evaluation of these new nitrate-thiol-hybrid prodrugs. These prodrugs might
      release NO in vivo after biotransformation without the use of endogenous
      reductives. None of these prodrugs released NO spontaneously when dissolved in
      buffer solution, but they did activate soluble guanylyl cyclase and induced
      vasodilatation of phenylephrine-pretreated male Wistar rat aorta in a potency
      range between that of isosorbiddinitrate and glycerole trinitrate.

PMID- 10889316
TI  - Synthesis of oxypropanolamine derivatives of 3,4-dihydro-2H-1,4-benzoxazine, beta
      adrenergic affinity, inotropic, chronotropic and coronary vasodilating
      activities.
AB  - Aseries of oxypropanolamine derivatives of 3,4-dihydro-2H-1,4-benzoxazine were
      synthesized and evaluated for inotropic, chronotropic and coronary vasodilating
      activities in the canine heart, affinity to beta(1)-adrenergic receptor in turkey
      erythrocytes and affinity to the beta(2)-adrenergic receptor in the rat lung.
      Among these compounds, 4-acetyl-6-(3-tert-butylamino-2-hydroxy)propoxy-3,4
      dihydro-2H-1,4-benzoxazine showed 2.1-fold more potent affinity to the beta(1)
      receptor than propranolol and 7-(3-tert-butylamino-2-hydroxy)propoxy-N-butyryl
      3,4-dihydro-2H-1,4-benzoxazine showed 2.5-fold more potent affinity to the
      beta(2) receptor and furthermore 4386-fold more potent selectivity to the beta(2)
      receptor than propranolol. In addition, 4-acetyl-6-[3-(3,4-dimethoxybenzyl)amino
      2-hydroxy]propoxy-3,4-dihydro-2H-1,4-benzoxazine showed 1.1-fold more potent
      affinity to the beta(1) receptor than propranolol and also 1147-fold more potent
      selectivity to the beta(1) receptor. With a few exceptions, negative inotropic
      and chronotropic actions of these compounds were dependent on the size of the 4
      substituent obeying the order: unsubstituted < acetyl < propanoyl < butanoyl,
      while the benzoyl substituent conferred even stronger negative actions in the 6
      oxypropanolamine derivatives. Neither negative inotropic and chronotropic actions
      related with affinity to beta(1)-adrenoceptor nor coronary vasodilator action
      related with affinity to beta(2)-adrenoceptor were observed. 4-acetyl-7-[3-(3,4
      dimethoxybenzyl)amino-2-hydroxy]propoxy-3,4-dihydro-2H-1,4-benzoxazine exerted
      potent positive inotropic, chronotropic and coronary vasodilating actions. The
      inotropic and chronotropic actions of the latter compound may be attributed to
      the release of intrinsic catecholamines, as concluded by the absence of beta(1)
      adrenoceptor affinity and disappearance of activity in the presence of a beta
      blocker.

PMID- 10889317
TI  - beta(1)- and beta(2)-Adrenoceptor antagonist activity of a series of para
      substituted N-isopropylphenoxypropanolamines.
AB  - To further explore the structure-activity relationships of beta-adrenoceptor
      (beta-AR) antagonists, a series of 25 para-substituted N-isopropylphenoxy
      propanolamines were synthesised, nine of which are new compounds. All have been
      examined for their ability to antagonise beta(1)-ARs in rat atria and beta(2)-ARs
      in rat trachea. Substitution in the para-position of the phenyl ring is thought
      to confer beta(3)-specificity and the selectivity of these compounds for the
      beta(1)-AR ranges from 1.5-234. None of the compounds tested were selective for
      the beta(2)-AR. Of the 25 compounds studied, 22 had reasonable (pA(2) > 7)
      potencies for the rat beta(1)-AR. Only compound 1 displayed reasonable (pA(2) >
      7) potency for the rat beta(2)-AR. Twenty two compounds were used as the training
      set for comparative molecular field analysis (CoMFA) of antagonist potency
      (pA(2)) at the rat beta(1)- and beta(2)-ARs. The inclusion of a number of
      additional physical characteristics improved the QSAR analysis over models
      derived solely using the CoMFA electrostatic and steric fields. The final models
      predicted the beta(1)- and beta(2)-AR potency of the compounds in the training
      set with high accuracy (r(2) = 0.93 and 0.86 respectively). The final beta(1)-AR
      model predicted the beta(1)-potencies of two out of the three test compounds, not
      included in the training set, with residual pA(2) values < -0.14, whereas the
      test compounds were not as well predicted by our final beta(2)-AR model (residual
      pA(2) values < -0.38).

PMID- 10889318
TI  - Protease inhibitors - Part 3. Synthesis of non-basic thrombin inhibitors
      incorporating pyridinium-sulfanilylguanidine moieties at the P1 site.
AB  - Using benzamidine and sulfaguanidine as lead molecules, three series of
      derivatives have been prepared by reaction of sulfaguanidine with pyrylium salts,
      with the pyridinium derivatives of glycine and with the pyridinium derivatives of
      beta-alanine, respectively. The new compounds were assayed as inhibitors of two
      serine proteases, thrombin and trypsin. The study showed that in contrast to the
      leads, possessing K(I)'s around 100-300 nM against thrombin, and 1200-1500 nM
      against trypsin, respectively, the new derivatives showed inhibition constants in
      the range of 15-50 nM against thrombin, whereas their affinity for trypsin
      remained relatively low. Derivatives of beta-alanine were more active than the
      corresponding Gly derivatives, which in turn were more inhibitory than the
      pyridinium derivatives of sulfaguanidine possessing the same substitution pattern
      at the pyridinium ring. Thus, the present study proposes two novel approaches for
      the preparation of high affinity, specific thrombin inhibitors: a novel S1
      anchoring moiety in the already large family of arginine/amidine-based
      inhibitors, i.e., the SO(2)N=C(NH(2))(2) group, and novel non-peptidomimetic
      scaffolds obtained by incorporating alkyl-/aryl-substituted-pyridinium moieties
      in the hydrophobic binding site(s). The first one is important for obtaining
      bioavailable thrombin inhibitors, devoid of the high basicity of the commonly
      used arginine/amidine-based inhibitors, whereas the second one may lead to
      improved water solubility of such compounds due to facilitated salt formation as
      well as increased stability at hydrolysis (in vivo).

PMID- 10889319
TI  - Synthesis and antispasmodic activity of analogues of natural pterosins.
AB  - The synthesis of an extensive range of analogues of natural pterosins using
      modified Heck coupling is reported. The smooth muscle relaxant activity of these
      compounds has been examimed. Several compounds with significant smooth muscle
      relaxant activity have been identified.

PMID- 10889320
TI  - 3-Pyrazolone analogues of the 3-isoxazolol metabotropic excitatory amino acid
      receptor agonist homo-AMPA. Synthesis and pharmacological testing.
AB  - We have previously shown that the higher homologue of (S)-glutamic acid [(S)
      Glu], (S)-alpha-aminoadipic acid [(S)-alpha-AA] is selectively recognized by the
      mGlu(2) and mGlu(6) subtypes of the family of metabotropic glutamic acid (mGlu)
      receptors. Furthermore, a number of analogues of (S)-alpha-AA, in which the
      terminal carboxyl group has been replaced by various bioisosteric groups, such as
      phosphonic acid or 3-isoxazolol groups, have been shown to interact selectively
      with different subtypes of mGlu receptors. In this paper we report the synthesis
      of the 3-pyrazolone bioisosteres of alpha-AA, compounds (RS)-2-amino-4-(1,2
      dihydro-5-methyl-3-oxo-3H-pyrazol-4-yl)butyric acid (1) and (RS)-2-amino-4-(1,2
      dihydro-1,5-dimethyl-3-oxo-3H-pyrazol-4-yl)butyric acid (2). At a number of steps
      in the reaction sequences used, the reactions took unexpected courses and
      provided products which could not be transformed into the target compounds, and
      attempts to synthesize the 2,5-dimethyl isomer of 2, compound 3, failed. An X-ray
      crystallographic analysis of the intermediate 1,2-dihydro-4-(2-hydroxyethyl)-2,5
      dimethyl-3H-pyrazol-3-one (5b) confirmed the expected regioselectivity of the
      reaction between methylhydrazine and alpha-acetylbutyrolactone (4). Neither 1 nor
      2 showed significant effects at the different types of ionotropic glutamic acid
      receptors or at mGlu(1a) (group I), mGlu(2) (group II), and mGlu(4a) and mGlu(6)
      (group III) receptors, representing the three indicated groups of mGlu receptors.

PMID- 10889321
TI  - Synthesis and pharmacological evaluation of carboxamide derivatives as selective
      serotoninergic 5-HT(4) receptor agonists.
AB  - A number of new carboxamide derivatives were synthesized. The affinity of these
      compounds for the serotoninergic 5-HT(4) receptor was evaluated by use of
      radioligand-binding techniques. The agonistic activity was evaluated as the
      contractile effect of the ascending colon isolated from guinea-pigs. Among these
      compounds, 4-amino-5-chloro-2-methoxy-N-[1-[2-[(methylsulfonyl)amino]ethly]-4
      piperidinylmethyl]benzamide (24) showed a high affinity for the 5-HT(4) receptor
      (Ki = 9.6 nM). Compound 24 displayed a higher affinity for 5-HT(4) receptors than
      the other receptors, including, 5-HT(3) and dopamine D(2) receptors. In addition,
      compound 24 was confirmed to be a potent 5-HT(4) receptor agonist (ED(50) = 7.0
      nM). An interaction model between compound 24 and 5-HT(4) receptor was proposed.

PMID- 10889322
TI  - Synthesis and antioxidant activity of new tetraarylpyrroles.
AB  - The synthesis and in vitro antioxidant activity of 17 new tetraarylpyrroles are
      investigated by 2 tests highly documented in the literature: capability to
      prevent Fe(2+)-induced lipid peroxidation on microsomes, which is a membrane
      preparation rich in polyunsaturated fatty acids, and direct scavenging effect on
      a stable free radical, 1,l-diphenyl-2-picryl-hydrazyl (DPPH). For the Fe(2+)
      induced microsomal lipid peroxidation system, the results show that molecules
      which possess 2-pyrazinyl or 2-pyridyl in the 3- and 4-positions on the pyrrole
      ring are the most efficient. Introduction of methoxy groups on the phenyl ring in
      the 2- and 5-positions increases the effects but the higher activity is obtained
      with 2-furyl or 2-thienyl. The only compounds which possess a direct scavenger
      effect on trapping the stable free radical DPPH are those which have 2-pyridyl in
      the 3- and 4-positions and 2-furyl or 2-thienyl in the 2- and 5-positions.

PMID- 10889323
TI  - Synthesis and anti-inflammatory activity of N-substituted 2-oxo-2H-1-benzopyran-3
      carboxamides and their 2-iminoanalogues.
AB  - Aseries of N-arylsubstituted 2-imino-2H-1-benzopyran-3-carboxamides 3a and b and
      2-oxo-2H-1-benzopyran-3-carboxamides 4a-h were synthesized and evaluated for
      their anti-inflammatory activity in carrageenan-induced rat paw oedema assays and
      in acetic acid-induced peritonitis tests in albino rats. The resulting products
      were found to be active anti-inflammatory agents and their effects were
      comparable to that of piroxicam as the reference compound. In the consideration
      of the efficacy of the compounds in these assays, 2-imino/oxo-2H-1-benzopyran-3
      carboxamides 3a and b and 4a-h were further studied at graded doses for their
      acute toxicity (ALD(50)) in albino mice and were essentially non-toxic at the
      highest dose tested.

PMID- 10889324
TI  - Research on heterocyclic compounds, XLI. 2-Phenylimidazo
AB  - The synthesis of a group of 2-phenylimidazo[1,2-b]pyridazine-3-acetic esters and
      acids is described. The structures of the new compounds are supported by 1H-NMR
      spectra. These compounds were tested in vivo for their anti-inflammatory,
      analgesic and ulcerogenic activity. All new compounds showed remarkable anti
      inflammatory action in the carrageenan rat paw oedema (one third of that for
      indomethacin) but no significant analgesic activity in the acetic acid writhing
      test together with negligible ulcerogenic action, and were also found to be
      lacking inhibitory activity on cyclooxygenase in vitro.

PMID- 10889325
TI  - 2-Substituted indazoles. Synthesis and antimicrobial activity.
AB  - 2-Isothiocarbamoyl substituted fused pyrazolines and their S-alkyl derivatives
      were prepared as potentially antimicrobial agents. Conventional methods were used
      to synthesize the novel derivatives starting from cyclic unsaturated ketones and
      thiosemicarbazide under acidic catalyst. These cyclizations yielded only one
      diastereoisomer of 3-H, 3a-H cis. The alkylations were performed applying alkyl
      halides. The structures of the new compounds, including configurations and
      conformations, were elucidated by NMR spectroscopy, also making use of 2D-HSC,
      DEPT and DNOE measurements. The S-alkyl derivatives were evaluated for activity
      against Gram-negative and Gram-positive bacteria and their in vitro toxicity was
      determined on HeLa cells. The structure-activity relationship was also studied.

PMID- 10889326
TI  - Phosphodiesterase 4 inhibitors, structurally unrelated to rolipram, as promising
      agents for the treatment of asthma and other pathologies.
AB  - An increase of cyclic adenosine and guanosine monophosphate (cAMP and cGMP) level
      can be achieved by inhibition of phosphodiesterases (PDEs), which are the enzymes
      responsible for the conversion of these second messengers into the corresponding
      5-monophosphate inactive counterparts. The high heterogeneity in PDE families and
      in their tissue distribution, as well as their different functional role, make
      these enzymes very attractive targets for medicinal chemists. The PDE 4 family is
      particularly abundant in immunocompetent cells, where an increase of cAMP leads
      to the inhibition of the synthesis and release of pro-inflammatory mediators,
      cytokines and active oxygen species. Moreover PDE 4 inhibitors are able to reduce
      bronchial smooth muscle tone in vitro and show bronchodilatory effects in vivo.
      Thus, the current therapy for asthma, which is based on a combination of beta(2)
      agonists and corticosteroids, could be replaced by treatment with PDE 4
      inhibitors. This review mainly covers PDE 4 inhibitors structurally related to
      xanthines and Nitraquazone, which appear to be very attractive models for the
      synthesis of novel PDE 4 inhibitors potentially useful for the treatment of
      asthma, chronic pulmonary obstructive disease and some autoimmune diseases. These
      compounds could be devoid of the central side-effects (nausea, vomiting,
      headache) of the archetypal Rolipram, which hampered its development as a drug.
      The review also highlights the novel structural classes of PDE 4 inhibitors
      recently reported in the literature.

PMID- 10889327
TI  - Palladium(II) complexes of NS donor ligandsderived from S-methyl-dithiocarbazate,
      S-benzyldithiocarbazateand thiosemicarbazide as antiamoebic agents.
AB  - Synthesis of palladium(II) complexes of the type [PdLCl(2)] (where L = Schiff
      bases derived from 2-acetylpyridine and S-methyldithiocarbazate, S
      benzyldithiocarbazate or thiosemicarbazide) have been isolated by the reaction of
      [Pd(DMSO)(2)C1(2)] and respective ligands. The complexes have been characterized
      by elemental analyses, IR, 1H-NMR, electronic spectra and thermogravimetric
      analysis. It is concluded that the thionic sulphur and the azomethine nitrogen
      atoms of the ligands are bonded to the metal ion. Assessment of antiamoebic
      activity against Entamoeba histolytica (strain HK-9) was done by using a
      microdilution method. [Pd(2-Acpy-SMDT)C1(2)] and Pd(2-Acpy-SBDT)C1(2)] have shown
      greater activity, whereas [Pd(2-Acpy-TSC)C1(2)] showed similar activity as
      metronidazole in vitro.

PMID- 10889328
TI  - Growth hormone secretagogues derived from NN703 with hydrazidesas c-terminal.
AB  - A series of GH secretagogues based on modifications in the C-terminal of NN703 is
      reported. The C-terminal N-methyl amide of NN703 has been replaced with alkylated
      hydrazides in order to decrease the volume of distribution and identify GH
      secretagogues with shorter duration of action. Most of the prepared compounds
      show high potency in a rat pituitary assay. Subsequent to an initial in vivo
      screening in dogs, four compounds were selected for further pharmacological and
      pharmacokinetic evaluation. The four compounds showed oral bioavailability around
      35% and equipotency in vitro compared to NN703. The relationship between
      lipophilicity and volume of distribution is discussed and it is speculated
      whether the lower volume of distribution is attributed to the observed higher in
      vivo potency and shorter plasma elimination half-life.

PMID- 10889329
TI  - The pyrrole moiety as a template for COX-1/COX-2 inhibitors.
AB  - Aroyl- and thiophene-substituted pyrrole derivatives have been synthesized as a
      new class of COX-1/COX-2 inhibitors. The inhibition of COX-1 was evaluated in a
      biological system using bovine PMNLs as the enzyme source, whereas LPS-stimulated
      human monocytes served as the enzyme source for inducible COX-2. The
      determination of the concentration of arachidonic acid metabolites was performed
      by HPLC for COX-1 and RIA for COX-2. Variation of the substitution pattern led to
      a series of active compounds which showed inhibition for COX-1 and COX-2.
      Structural requirements for the development of COX-1/COX-2 inhibitors are
      discussed.

PMID- 10889330
TI  - Spirostanols obtained by cyclization of pseudosaponin derivatives and comparison
      of anti-platelet agglutination activities of spirostanol glycosides.
AB  - Naturally occurring saponins 3 and 4 have a normal type F ring and alpha-arranged
      CH(3)-21 group. Treatments of pseudosaponin peracetates 18 and 19 derived from 3
      and 4, respectively, with alcoholic KOH, followed by acidification with acetic
      acid, gave spirostanols 20 and 22 having iso type F rings as major products.
      Structural analyses of sapogenins and saponins derived from pseudo derivatives
      11, 12, 18 and 19 were performed by comparisons of their 1H-NMR spectral data and
      the X-ray analytical data of 3-O-p-bromobenzoyl sarsasapogenin 7, 3-O-acetyl
      diosgenin 13 and saponin 20. The mechanisms of ring-closure reaction of the side
      chain at C-22 of pseudosapogenins and pseudosaponins were deduced using
      stereomodels of the spirostanols derived from 11 under various reaction
      conditions. Inhibitory activities of saponin diglycosides 3, 4, 20, 21 and 25 on
      human platelet agglutinations induced by ADP and ristocetin were compared.

PMID- 10889331
TI  - New gamma-fluoromethotrexates modified in the pteridine ring: synthesis and in
      vitro immunosuppressive activity.
AB  - Our continuing program to develop new antifolate drugs useful against rheumatoid
      arthritis led us to modify the pteridine ring of gamma-fluoromethotrexate.
      Pyrrolopyrimidine derivatives 1e and 1t were found to exhibit potent suppressive
      effects on the responses of both T and B cells to mitogens, although
      tetrahydropyridopyrimidine derivatives 2e and 2t and quinazoline derivatives 3e,
      3t and 4e showed very weak suppressive activities. Thus, conversion of the
      pteridine ring of gamma-fluoromethotrexate to a pyrrolopyrimidine ring led to a
      new potential antirheumatic compound.

PMID- 10889332
TI  - Synthesis and antitubercular activity of 3-aryl substituted-2-[1H(2H)benzotriazol
      1(2)-yl]acrylonitriles.
AB  - A series of 22 3-aryl substituted-2-(1H(2H)-benzotriazol-1(2)-yl)acrylonitriles
      was synthesized for a preliminary in vitro evaluation of antitubercular activity
      according to an international program with the Tuberculosis Antimicrobial
      Acquisition & Coordinating Facility (TAACF). This work reports the synthetic
      approach and analytical and spectroscopic characterization (UV, IR, 1H- and 13C
      NMR) of all compounds synthesized. Several compounds showed an interesting
      activity in the preliminary screening with a percent growth inhibition of the
      virulent Mycobacterium tuberculosis between 40 and 99% at the concentration of
      12.5 microg/mL. The most effective derivatives E-5a and E-5e were also tested
      against M. avium in vitro.

PMID- 10889333
TI  - Synthesis and antitumour activity of 4-hydroxy-2-pyridone derivatives.
AB  - 4-hydroxy-2-pyridone derivatives 2 were prepared by reaction of 3-amino-3
      dialkylaminopropenoates with bis(2,4, 6-trichlorophenyl)malonate. These compounds
      were further reacted with a set of aldehydes to give bis(pyridyl)methanes 3 and
      4. The newly synthesized compounds 2, 3 and 4 were evaluated in vitro as
      antitumour agents against 60 human tumour cell lines. Some derivatives exhibit
      tumour growth inhibition activity. In particular, derivative 4g, the most active
      of the series, possesses significant activity on all cell lines at concentrations
      ranging from 1 x 10(-6) to 1 x 10(-5) M.

PMID- 10889334
TI  - Apoptotic cell death of cerebellar granule neurons in genetically ataxia (ax)
      mice.
AB  - An autosomal recessive neurological mutant, ataxia (ax) mouse, was investigated
      to determine whether neuronal cell death occurs in the brain. The brains of
      homozygotes (ax(J)/ax(J)) and phenotypically normal littermates (ax(J)/+ or +/+)
      aged at 23-38 days were examined by the terminal dUTP nick-end-labeling (TUNEL)
      method. A few TUNEL-positive cells were observed in the granule cell layer of the
      cerebellum, the dentate gyrus, and the olfactory bulb of normal mice. In the
      affected mice, the number of TUNEL-positive cells was significantly increased in
      the cerebellum, particularly in the granule cell layer, compared to normal
      littermates. The findings suggest that ax mice will be useful as a model for
      studies on the genetic basis of apoptotic neuronal cell death.

PMID- 10889335
TI  - Intracortical excitatory and inhibitory phenomena to paired transcranial magnetic
      stimulation in healthy human subjects: differences between the right and left
      hemisphere.
AB  - Intracortical inhibition (ICI) and facilitation (ICF) to paired magnetic stimuli
      reflect the activation of interneuronal circuits within the motor cortex.
      Intersubjects physiological variability of these phenomena, partly limits the
      usefulness of such method. Therefore, interhemispheric ICI/ICF differences might
      represent a more sensitive and less variable neurophysiological parameter to test
      the motor cortex excitability. Motor evoked potentials from the hand muscles were
      recorded in ten healthy subjects in a paired-pulse paradigm. Interstimulus
      intervals (ISIs) from 1 to 50 ms were used. The time course of ICI and ICF in the
      two hemispheres is consistent with minimal interhemispheric asymmetries. The
      interhemispheric differences of ICI and ICF could be a valuable
      neurophysiological marker for the diagnosis, prognosis and follow-up of
      neurological diseases characterized by monohemispheric damage and lateralized
      motor deficits.

PMID- 10889336
TI  - Presence of gamma-aminobutyric acid transporter mRNA in interneurons and
      principal cells of rat hippocampus.
AB  - After release, neurotransmitters are removed from the extracellular space by high
      affinity uptake. Specific sodium-dependent transporters serve this function for
      the inhibitory transmitter gamma-aminobutyric acid (GABA). However, it is largely
      unknown to which proportion GABA is taken up by GABAergic interneurons, glia
      cells or principal neurons. We analyzed the distribution of mRNA for the main
      GABA-transporter subtype in the hippocampus, GAT-1, in adult rats. Most
      interneurons were strongly stained for GAT-1 mRNA, indicating re-uptake by the
      GABA-releasing cells. Surprisingly, prominent signals for GAT-1 were also found
      throughout the principal cell layers (granule and pyramidal cells). These data
      indicate that GABA transporters may be present in non-GABAergic projection cells
      of the rat hippocampus which contribute to the clearance of GABA from the
      extracellular space.

PMID- 10889337
TI  - Analyses of Gerstmann-Straussler syndrome with 102Leu219Lys using monoclonal
      antibodies that specifically detect human prion protein with 219Glu.
AB  - Two monoclonal antibodies that specifically detect human prion protein (PrP) were
      developed. The epitope of both antibodies was mapped using fusion proteins of
      glutathione-S-transferase and PrP peptides to the C-terminal region encompassing
      the polymorphic 219 residue. The antibodies recognized human PrP with 219Glu but
      not that with 219Lys. The unique property of the antibodies was utilized to
      determine the allelic origin of abnormal PrP deposited in the brain of a patient
      with Gerstmann-Straussler syndrome (GSS) with 102Leu/219Lys encoded by the same
      allele. Abnormal PrP was exclusively of mutant allelic origin, suggesting that
      219Lys may be permissive to the formation of abnormal PrP in GSS. The antibodies
      may help to explore the relationship of 219Glu/Lys polymorphism to the
      pathogenesis of human prion diseases.

PMID- 10889338
TI  - The medullary cerebrovascular vasodilator area mediates cerebrovascular
      vasodilation and electroencephalogram synchronization elicited from cerebellar
      fastigial nucleus in Sprague-Dawley rats.
AB  - We investigated whether the medullary cerebrovasodilator area (MCVA), a region of
      ventral medulla mediating elevations of regional cerebral blood flow (rCBF) and
      electroencephalogram (EEG) synchronization elicited in cerebral cortex from
      stimulation of reticulospinal neurons of rostral ventrolateral medulla (RVLM),
      also mediates comparable responses from the cerebellar fastigial nucleus (FN). In
      spinalized rats, electrical stimulation of MCVA, RVLM or FN elevated rCBF and
      synchronized the EEG. The FN-evoked responses were significantly attenuated or
      blocked by bilateral lesions of MCVA. The MCVA is a novel region of medullary
      reticular formation mediating actions of medullary and cerebellar centers on rCBF
      and EEG to link visceral centers of brainstem and cerebral cortex.

PMID- 10889339
TI  - gamma-aminobutyric acid- and glycine-immunoreactive neurons postsynaptic to
      substance P-immunoreactive axon terminals in the superficial layers of the rat
      medullary dorsal horn.
AB  - gamma-Aminobutyric acid (GABA)ergic and glycinergic neurons were examined light-
      and electron-microscopically in laminae I and II of the medullary dorsal horn
      (MDH, i.e. spinal trigeminal nucleus caudalis in the rat). The majority of GABA-
      and glycine (Gly)-immunoreactive (-ir) neurons showed both GABA- and Gly
      immunoreactivities (-IRs). Noxious stimulation (subcutaneous injection of
      formalin into perioral regions) induced Fos-IR in some of GABA- and Gly-ir
      neurons. GABA- and Gly-ir neuronal profiles were postsynaptic to substance P-ir
      axon terminals. These results suggest that nociceptive information being carried
      by primary afferent SP-fibers may be relayed directly to GABAergic and
      glycinergic neurons in laminae I and II of the MDH.

PMID- 10889340
TI  - Inhibition of vitamin B12 metabolism by OH-cobalamin c-lactam in rat
      oligodendrocytes in culture: a model for studying neuropathy due to vitamin B12
      deficiency.
AB  - Vitamin B12 is implicated in methylation processes. Myelin basic protein is
      methylated on one arginine group. A defect in methylation could produce an
      unstable protein, leading to neurological disorders. In order to study myelin
      basic protein, we have developed the cultures of newborn rat oligodendrocytes in
      vitamin B12-depleted medium. As these cells do not grow without serum, vitamin
      B12 is always present. We overcame this problem by using OH-cobalamin c-lactam,
      an antagonist of B12. To ensure that the system was vitamin B12 deficient, we
      measured the concentrations of homocysteine and methylmalonic acid whose
      accumulations reflect a vitamin B12 deficiency. Methylmalonic acid was measured
      by mass spectrometry and homocysteine by HPLC. We obtained a powerful model for
      studying the influence of B12 deficiency on the synthesis of myelin compounds.

PMID- 10889341
TI  - Age-related changes of neuronal counts in the human pedunculopontine nucleus.
AB  - Cholinergic neurons in the basal forebrain and the upper brainstem undergo
      changes during aging and in dementia of the Alzheimer type, Parkinson's disease
      and progressive supranuclear palsy. Little is known about the effect of age on
      neurons in the tegmental pedunculopontine nucleus. Cholinergic neurons revealed
      by choline acetyltransferase immunohistochemistry were quantified in the brains
      of 20 subjects who died without neurological disorder between 28 and 101 years of
      age. A U-shaped relationship between cell counts and age was found, namely, a
      decrease in counts between 28 and 70, a minimum between 80 and 91 years of age,
      and, in four subjects aged 98-101 years counts comparable to those of subjects
      having died between 28 and 65 years. The findings suggest that the loss of
      cholinergic pedunculopontine nucleus neurons is not linear. In centenarians age
      related neuronal decrease in pedunculopontine nucleus neurons may be slower or
      the stock of pedunculopontine nucleus neurons greater than in subjects dying
      earlier.

PMID- 10889342
TI  - Loose ligation of the rat sciatic nerve is accompanied by changes in the
      subcellular content of protein kinase C beta II and gamma in the spinal dorsal
      horn.
AB  - This study examined whether loose ligation of the sciatic nerve was accompanied
      by specific changes in protein kinase C (PKC) betaII and gamma isozymes in the
      spinal dorsal horn. The isozyme staining pattern was visualized with
      immunocytochemistry. Their content in subcellular fractions was estimated from
      Western immunoblots. In control animals, PKC betaII immunoreactivity extended
      from lamina I into lamina III, while PKC gamma immunoreactivity was concentrated
      within laminae II and III. In ligated animals exhibiting thermal hyperalgesia,
      the content of both PKC betaII and gamma in the synaptosomal membrane fraction,
      but not crude cytosolic fraction, was significantly greater by an average of 40%
      from their respective controls. These data support suggestions that peripheral
      nerve injury engenders plastic changes in the dorsal horn to contribute to the
      development of persistent pain.

PMID- 10889343
TI  - Effects of sodium azide on the secretion of soluble amyloid-beta precursor
      protein and the accumulation of beta-amyloid(1-40) in cultured chick neurons.
AB  - Sodium azide has been reported in the literature to reduce the release of
      secreted amyloid beta-precursor protein (AbetaPPs) and to produce a large
      increase in the cellular level of an 11.5 kDa C-terminal AbetaPP derivative
      containing the beta-amyloid (Abeta) sequence. Here we report that 1 mM of sodium
      azide, reduced the constitutive AbetaPPs secretion from cultured embryonic chick
      neurons after 12 h of incubation. After 24 h of incubation there was a modest
      increase in lactate dehydrogenase (LDH) release and no change in MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction, suggesting that
      the reduced AbetaPPs secretion was not due to the cell toxic effects of NaN(3).
      However, NaN(3) reduced the accumulation of Abeta(1-40) in the cell lysates and
      decreased the acetylcholine esterase activity both in cell culture media and in
      cell lysates. It is concluded that the effect of NaN(3) upon AbetaPP metabolism
      in the chick cultured neurons may be a rather non-specific effect.

PMID- 10889344
TI  - Characterization of ZFOR1, a putative delta-opioid receptor from the teleost
      zebrafish (Danio rerio).
AB  - ZFOR1 is a putative opioid receptor from zebrafish brain which has 66% homology
      with the mammalian delta-opioid receptor. When expressed in HEK293 cells ZFOR1
      bound the non-selective opioid antagonist [(3)H]diprenorphine with high affinity.
      However, the binding of this ligand was not readily displaced by opioids
      selective for mu, delta or kappa opioid receptors (affinities>1000 nM). Rather
      non-selective ligands showed good affinity, as did the non-peptide delta-ligand
      BW373U86 (Ki 69 nM), the delta-antagonist naltrindole (Ki 28 nM) and the peptide
      beta-endorphin (Ki 37 nM). Agonist binding to the receptor encoded by ZFOR1
      receptor stimulated the binding of [(35)S]GTPgammaS confirming coupling to G
      proteins. Study of the receptor should contribute to understanding of the
      evolution of the opioid system.

PMID- 10889345
TI  - Phospholipase A2 activity is decreased selectively in the hippocampus of aged
      apolipoprotein E deficient mice.
AB  - Because apolipoprotein E (ApoE) deficient mice have cognitive deficits (Neurosci.
      Lett., 199 (1995) 1-4; Neuroscience, 92 (1999) 1273-1286; Brain Res., 752 (1997)
      189-196) that may involve decreased phospholipase A(2) (PLA(2)) activity
      (Neuroscience, 92 (1999) 1273-1286), striatal, hippocampal, and parieto-temporal
      PLA(2) activity was measured in cytosol from 3 and 20-month-old ApoE deficient
      and control mice. Samples were homogenized and cytosol prepared by
      ultracentrifugation. PLA(2) activity in each cytosolic fraction was measured in
      triplicate using a continuous fluorometric assay (J. Neurosci. Methods (2000) in
      press). In 3-month-old animals, there was a trend for decreased hippocampal
      PLA(2) activity between groups. In 20-month-old animals, hippocampal PLA(2)
      activity was significantly (P=0.0304) decreased nearly 20% in ApoE deficient mice
      as compared to age-matched control mice. No differences were found in other brain
      regions, although activity in the striatal samples were nearly 65% less than in
      the other two regions.

PMID- 10889346
TI  - Resection of sciatic nerve re-triggers central sprouting of A-fibre primary
      afferents in the rat.
AB  - We have investigated whether nerve injury or target deprivation is responsible
      for the injury induced central sprouting of A-fibres. Cholera toxin B subunit
      conjugated horseradish peroxidase was used to trace the termination of A-fibre
      primary afferents. Transection of the sciatic nerve induces central sprouting of
      sciatic myelinated A-fibre primary afferents into the spinal dorsal horn lamina
      II, which normally is the termination site of unmyelinated C-fibre primary
      afferents. The sprouting A-fibre terminals withdrew from lamina II after six to
      eight months. A second cut to the previously sectioned and ligated sciatic nerve
      re-triggered the central sprouting of A-fibre primary afferents into the spinal
      dorsal horn lamina II, suggesting that nerve injury per se rather than the
      deprivation of target tissues is the cause of central sprouting of A-fibre
      primary afferents.

PMID- 10889347
TI  - Morphological distinction between vasodilator and secretomotor neurons in the
      pterygopalatine ganglion of the cat.
AB  - We investigated whether vasodilator and secretomotor ganglion neurons are
      morphologically distinguishable from each other in the parasympathetic ganglion
      of the cat. When Cholera toxin B subunit, a retrograde tracer, was injected into
      the palatine gland, both large and small ganglion neurons were retrogradely
      labeled in the pterygopalatine ganglion. On the other hand, when the tracer was
      injected into gland-free areas (the upper gingiva or epidural space), all neurons
      labeled in the ganglion were small in size. Thus, it was assumed that small and
      large neurons labeled in the ganglion represented, respectively, vasomotor and
      secretomotor and neurons [corrected].

PMID- 10889348
TI  - Developmental increase in (3)H-muscimol binding to the gamma-aminobutyric acid(A)
      receptor in hypothalamic and limbic areas of the rat: why is the ventromedial
      nucleus of the hypothalamus an exception?
AB  - Using in vitro autoradiography to measure binding of the gamma-aminobutyric
      acid(A) (GABA(A)) receptor agonist, muscimol, we examined male and female rats on
      postnatal days 1, 5, 10, and 20. There were no sex differences in muscimol
      binding in any hypothalamic or limbic regions examined. However, all regions
      exhibited a developmental increase in the density of binding, except the
      ventromedial nucleus (VMN) of the hypothalamus. We have previously shown that the
      adult VMN is the only hypothalamic nucleus containing an abundance of the alpha2
      subunit of the GABA(A) receptor and lack of the alpha1 subunit. We hypothesize
      that the lack of alpha1 may be causally related to the lack of increase in
      muscimol binding.

PMID- 10889349
TI  - Lipopolysaccharide increases arginine-vasopressin release from rat
      suprachiasmatic nucleus slice cultures.
AB  - The aim of this study was to determine whether Escherichia coli
      lipopolysaccharide at the doses of 25, 50 and 100 microM influences arginine
      vasopressin (AVP) secretion in young rat suprachiasmatic nucleus (SCN) neurons.
      Lipopolysaccharide administered in the medium for 3 h increased significantly the
      arginine-vasopressin release lasting up to 6 h after treatment. These results
      provide the first evidence that lipopolysaccharide influences AVP secretion in
      SCN neurons. Moreover, these findings may explain some central effects observed
      in vivo after lipopolysaccharide administration.

PMID- 10889350
TI  - Guanethidine evokes vasodilatation in guinea pig mesenteric artery by acting on
      sensory nerves.
AB  - In precontracted, endothelium-free guinea pig mesenteric artery rings, in which
      adrenergic vasoconstrictor responses had been eliminated, guanethidine (1-30
      microM) produced a vasodilatation of 69.3+/-4.4%. The vasodilatation was reduced
      89% by capsaicin (10 microM) or 55% by tetrodotoxin (10 microM), indicating
      mediation of this effect by primary sensory nerves. The nitric oxide synthase
      inhibitor N(omega)-nitro-L-arginine (100 microM, 30 min) but not its stereoisomer
      reduced the guanethidine vasodilatation by 70%. Blockade of monoamine uptake with
      ouabain (25 microM, 15 min) or cocaine (5 microM, 5 min) reduced the guanethidine
      induced vasodilatation by 85 and 67%, respectively. These results suggest that
      guanethidine produced vasodilatation by being transported into capsaicin
      sensitive primary sensory nerves where it functioned as a substrate for nitric
      oxide synthase to generate a vasodilatory substance.

PMID- 10889351
TI  - Clozapine downregulates 5-hydroxytryptamine6 (5-HT6) and upregulates 5-HT7
      receptors in HeLa cells.
AB  - Clozapine is an atypical antipsychotic with high affinity for several serotonin
      receptors. This drug causes paradoxical downregulation of 5-hydroxytryptamine(2A)
      (5-HT)(2A) receptors, but its modulation of other serotonin receptors has not
      been studied. We examined the effects of clozapine and several other drugs on the
      regulation of rat 5-HT(6) and 5-HT(7) receptors individually expressed in
      transfected HeLa cells. Both 5-HT(6) and 5-HT(7) receptor densities (B(max)) were
      reduced by 5-carboxamidotryptamine, an agonist, and methiothepin, an inverse
      agonist. Clozapine reduced 5-HT(6) B(max). This suggests that 5-HT(6) receptors
      are also paradoxically downregulated by the antagonist clozapine. 5
      Hydroxytryptamine(7) receptor B(max), on the other hand, was increased by
      clozapine. Clozapine's modulation of the 5-HT(6) and 5-HT(7) receptor levels may
      be important in the action of this atypical antipsychotic.

PMID- 10889352
TI  - Nuclear factor-kappa B activation in permanent intraluminal focal cerebral
      ischemia in the rat.
AB  - Nuclear factor-kappa B (NF-kappa B) is an oxidative stress responsive
      transcription factor known to be activated in response to transient middle
      cerebral artery intraluminal occlusion. Since oxidative stress activation may
      largely occur during reperfusion, the aim of this study was to determine if
      permanent middle cerebral artery intraluminal occlusion without reperfusion
      induces NF-kappa B activation and the relationship of NF-kappa B activation to
      HSP70 expression and neuronal cell death. Our results suggest that permanent
      intraluminal occlusion is sufficient to induce NF-kappa B activation 7 h after
      the onset of occlusion. Interestingly, this activation seems to occur
      specifically in dying neurons of the penumbra area devoid of any HSP70 neuronal
      immunoreactivity. These findings are consistent with the suggested protective
      role of HSP70 expression and suggest that NF-kappa B activation observed in the
      penumbra area has a role in neuronal cell death after permanent intraluminal
      cerebral ischemia.

PMID- 10889353
TI  - Hippocampal and striatal [(3)H]5-HT reuptake under acute stressors in two rat
      strains differing for their emotivity.
AB  - Spontaneously hypertensive rats and Lewis rats differ in their anxiety levels and
      in their serotonergic and corticotropic responses to stress. Since the 5-HT
      transporter plays a key role in 5-HT neurotransmission, we have analyzed whether
      hippocampal and/or striatal [(3)H]5-HT reuptake kinetics are altered by stress in
      a strain-dependent manner. It was found that forced swimming, treadmill running,
      or restraint for 30 min affected neither hippocampal nor striatal [(3)H]5-HT
      reuptake K(m) and V(max) values in the two rat strains. This study, which is the
      first to examine the impact of acute stress on [(3)H]5-HT reuptake with respect
      to the nature of the stressor, the brain region analyzed, and the rat strain,
      could reinforce the hypothesis that extracellular 5-HT levels during stress are
      representative of 5-HT release.

PMID- 10889354
TI  - Immunohistochemical study of the cyst of Besnoitia besnoiti.
AB  - The present study has been undertaken in order to provide information on the
      molecular structure of the cysts of Besnoitia besnoiti. To that end,
      immunohistochemical techniques have been used to investigate the expression of
      several enzymes and proteins implicated in the cellular membrane permeability of
      bradyzoites. Paraffin and frozen sections, which were obtained from subcutaneous
      tissue samples taken from naturally infected cattle (coming from northeast
      Spain), were treated with a panel of antibodies. These were specific for Na(+),
      K(+)-ATPase, alkaline phosphatase, calmodulin, S100 protein, heat shock proteins,
      hsp60, and hsp70. Positive-cysts for the said antibodies were found in 23.3% of
      the cows studied. Bradyzoites showed a positive immunoreaction in every positive
      cyst with respect to all these antibodies. In addition to the low percentage of
      positive animals, it is worth noting that positive and unstained cysts were
      observed in the same tissue section. These results suggest that bradyzoites may
      pass through both active and dormant metabolic phases.

PMID- 10889355
TI  - Prevalence and strain differentiation of Giardia intestinalis in calves in the
      Manawatu and Waikato regions of North Island, New Zealand.
AB  - Giardia intestinalis has been reported in newborn calves world-wide; however,
      information on the extent of G. intestinalis in New Zealand calves has to date
      been very limited. The current study attempted to establish the prevalence rate
      of G. intestinalis in calves up to 8 weeks old in New Zealand. More than 700 calf
      fecal specimens were collected during the spring calving seasons of 1998 and 1999
      from two regions in North Island, New Zealand (Manawatu and Waikato) and tested
      for the presence of G. intestinalis. In addition to determining the presence of
      G. intestinalis in newborn calves, sequence analysis was performed using specific
      amplification primers developed to target a section of the ribosomal DNA (rDNA).
      This locus is considered to be rapidly evolving, and therefore, suitable for use
      in the elucidation of phylogenetic relationships between G. intestinalis
      isolates. Sequencing was performed using G. intestinalis DNA extracted from cysts
      collected directly from the calf fecal matter. There was no culturing of the G.
      intestinalis isolates either in vivo or in vitro. Over 40% of all collected calf
      fecal specimens contained G. intestinalis cysts and rDNA sequence analysis
      revealed two different sequences among calf isolates. These sequence differences
      were not found to correspond to a particular season, geographical region or
      farming practice. Preliminary phylogenetic analysis suggests that these two rDNA
      sequence types are indicative of calf hosts.

PMID- 10889356
TI  - Neosporosis in water buffalo (Bubalus bubalis) in Southern Italy.
AB  - A study was carried on 1377 water buffalo serum samples from 50 farms in southern
      Italy to test the presence of Neospora caninum antibodies by indirect
      fluorescence antibody test (IFAT). Rabbit anti-buffalo immunoglobulins conjugated
      to fluorescein were used in the test. Fluorescence in sera dilutions above 1:200
      was considered as indicative of the presence of N. caninum antibodies. The
      overall prevalence of infection in the animals was 34.6%. The prevalence
      increased in relation to the age of subjects and most of the herds examined (82%)
      were found infected. In two farms abortions and neurological signs were reported.
      No suppurative inflammatory lesions were seen, but few protozoan-like cysts were
      observed on foetal tissues by histology.

PMID- 10889357
TI  - The prevalence and avidity of Toxoplasma gondii IgG antibodies in pigs from
      Brazil and Peru.
AB  - Raw or inadequately cooked pork is an important source of Toxoplasma gondii
      infection, and the infection rate in animals used as human food, is an important
      risk predictor. The prevalence of this infection was estimated in 396 sera from 5
      month old pigs obtained at abattoirs in Sao Paulo, Brazil (300) and Lima, Peru
      (96). The seroprevalence was higher in pigs from Peru (32.3%) as compared to
      Brazil (9.6%), as detected by ELISA and Western blot. Hemagglutination gave poor
      resolution which was not useful for the diagnosis of T. gondii infection.
      Specific antibody avidity is correlated with infection time, as shown in
      experimentally infected piglets. Using an arbitrary cut-off of 50% avidity index,
      Brazilian pigs were found to be more recently infected than Peruvian pigs. Pork
      should be considered a significant source of human T. gondii infection both in
      Brazil and Peru. Avidity assays could help in the detection of the time of T.
      gondii infection in pigs, allowing preventive management.

PMID- 10889358
TI  - Vaccination of mice against schistosoma bovis with a recombinant fatty acid
      binding protein from Fasciola hepatica.
AB  - Two strains of mice (NMRI and C57/BL) were each immunized with a 15kDa
      recombinant Fasciola hepatica fatty acid binding protein (FABP) (Fh15) and
      challenged percutaneously with Schistosoma bovis cercariae. C57/BL mice immunized
      with Fh15 had significant reductions in S. bovis worm burden recoveries (72%
      reductions over controls). When using NMRI mice, Fh15 in Freund's adjuvant failed
      to induce significant protection against S. bovis. In C57/BL mice, only
      antibodies to the IgG2a isotype increased after the second immunization and
      remained high through 8 weeks of S. bovis infection. This is the first time that
      a heterologous recombinant molecule from F. hepatica has been used in vaccination
      against S. bovis, obtaining a significant reduction in the number of worms in
      C57/BL mice.

PMID- 10889359
TI  - Can an increased intake of metabolizable protein affect the periparturient
      relaxation in immunity against teladorsagia circumcincta in sheep?
AB  - Within the overall hypothesis that the periparturient relaxation of immunity
      (PPRI) to gastrointestinal parasites has a nutritional basis, we studied whether
      an increased intake of metabolizable protein (MP) could affect the expression of
      immunity to Teladorsagia (Ostertagia) circumcincta of twin-bearing and -rearing
      Greyface ewes. Two sets of iso-energetic diets were formulated to provide either
      85% (L-) or 130% (H-) of the MP requirements during the last 6 weeks of pregnancy
      (-P) and the first 6 weeks of lactation (-L). Thirty ewes were allocated to LP or
      HP. Six ewes of each group were slaughtered after lambing (S(0)); the remaining
      24 ewes of each group were allocated to either LL or HL, thus creating four
      treatment combinations during lactation (LP/LL, LP/HL, HP/LL and HP/HL; n=12).
      Six ewes of each treatment combination were slaughtered at Week 3 (S(3)) or at
      Week 6 (S(6)) in lactation. The HP ewes were heavier at lambing, produced heavier
      lambs, had lower faecal egg counts (FECs), a lower concentration of plasma
      pepsinogen, a higher concentration of plasma albumin during late pregnancy and
      more abomasal globule leukocytes (GLs) but similar worm burdens at S(0) compared
      to the LP ewes. The LP/HL and HP/HL ewes had a higher calculated milk production
      than the LP/LL and HP/LL ewes. FECs increased for each treatment combination
      during the first 3 weeks of lactation. This increase concurred with fewer
      abomasal GLs at S(3) compared to S(0). The LP/HL and HP/HL ewes had a higher
      proportion of immature worms and more abomasal GLs than the LP/LL and HP/LL ewes
      at S(6). The FECs continued to increase during the second 3 weeks of lactation
      for the LP/LL ewes only, which concurred with an elevated plasma pepsinogen
      concentration and an absence of abomasal GLs at S(6). The plasma pepsinogen
      concentration decreased rapidly for the LP/HL ewes during lactation. We conclude
      that an increased intake of MP could enhance the expression of immunity to T.
      circumcincta of twin-bearing and -rearing Greyface ewes.

PMID- 10889360
TI  - Use of a 14.2 kDa recombinant Cooperia oncophora protein in an ELISA for herd
      health monitoring of nematode infections in first grazing season calves.
AB  - An ELISA using a recombinant 14.2kDa excretory/secretory Cooperia oncophora
      protein (CoES14.2 ELISA) was evaluated for estimating level of cumulative
      exposure to infective Cooperia larvae in first grazing season calves. Data from
      one experiment were used to obtain a quantitative relationship between IgG levels
      and cumulative exposure. That relationship was validated against data from
      another experimental study and from natural field studies. The latter included
      different pasture management strategies with or without an anthelmintic
      treatment. Validation involved 'predicting' cumulative exposure for the groups of
      calves in the latter two datasets based on observed IgG levels measured with the
      CoES14.2 ELISA, and subsequently comparing those 'predictions' with observed
      cumulative exposures. Generally, 'predicted' cumulative exposures correlated well
      to observed exposures (r values of 0.7-0.9). However, 'predicted' cumulative
      exposures underestimated observed exposures in the natural field studies.
      Anthelmintic treatments in some of the groups of the natural field studies
      reduced the 'prediction' accuracy of the CoES14.2 ELISA. This suggests that
      cumulative exposure in relation to IgG levels is more accurately defined by the
      total amount of host-parasite contact than by the cumulative number of larvae
      ingested. It is concluded that IgG levels measured with the CoES14.2 ELISA allow
      evaluating how much exposure to infection calves have experienced in the first
      grazing season.

PMID- 10889361
TI  - Clinical features of experimental trichinellosis in the raccoon dog (Nyctereutes
      procyonoides).
AB  - Three groups of six raccoon dogs (Nyctereutes procyonoides) were provided for the
      experiment: the first group was infected with pig-origin Trichinella spiralis,
      the second with raccoon dog-origin Trichinella nativa, and the third served as
      controls. Infection dose for both parasite species was 1000 larvae/kg of body
      weight, which led to intense final infection. Clinical signs, haematology and
      serum biochemistry with repeated blood samples were monitored up to 12 weeks post
      infection. The most significant findings were a short-term eosinophilia in
      peripheral blood from the end of the first week post-infection until the end of
      the third week, loss of weight, and mild anaemia. In the early phase of the
      infection, the animals had gastrointestinal signs, loss of appetite and
      diarrhoea. No specific differences in clinical findings could be noticed between
      the groups infected with T. nativa and T. spiralis. In contrast to the symptoms
      reported in human outbreaks, fever was not observed in any of the infected
      animals and serum levels of muscle-specific enzymes did not change. No acute
      phase response was observed in the enteral or parental phase of the infection.
      These findings indicate that because Trichinella spp. are very well adapted to
      the raccoon dog, it thus, could serve as the most crucial reservoir animal for
      sylvatic trichinellosis in Finland.

PMID- 10889362
TI  - Factors affecting the larvipositional activity of Oestrus ovis gravid females
      (Diptera: oestridae).
AB  - Observations of fly strikes or larvipositions (n=68 in 21 days of observation)
      were carried out in a herd of goats during the spring in Baja California Sur,
      Mexico in order to identify the climatic conditions favoring larviposition
      activity of gravid Oestrus ovis L. flies, as well as to investigate whether a
      mixture of some potentially useful compounds was involved in this behavior. Hand
      caught, tethered flies (n=43) were either exposed or unexposed to a combination
      of carbon dioxide, humidity, 1-octen-3-ol, butyric, propionic, acetic acid and
      acetone released from movable sheep and goat dummies under open field and cage
      conditions. Fly strikes occurred at temperatures greater than 20 degrees C, but
      mainly between 25 and 28 degrees C and from 116 to 838W m(-2) of solar
      irradiance. Few or no strikes were seen under moderate or strong wind, but did
      occur in a wide range of relative humidity. The chemicals applied did not improve
      the capacity of animal dummies to induce the flies to larviposit, but very
      irregular behavior was observed. Fourteen larvipositions were made on the dummies
      lacking chemical stimuli, so visual ability and movement by the dummies was very
      important in stimulation of the flies. Temperature appeared to be the main factor
      determining fly activity, but wind and solar irradiance also played important
      roles. Characteristics of O. ovis larviposition are discussed.

PMID- 10889363
TI  - Effects of psoroptes ovis infection and its control with an ivermectin controlled
      release capsule on growing sheep. 1. Evaluation of weight gain, feed consumption
      and carcass value.
AB  - To evaluate the prophylactic and therapeutic effects of an ivermectin controlled
      release capsule (IVM-CRC) on the productivity of growing sheep infested with
      Psoroptes ovis 24 male and 24 female Merino landrace lambs, 5-6 months old and
      weighing 21.2-35.0 kg, were used. Sixteen replicates of three animals were formed
      based on sex and Day 0 body weight. Within each replicate animals were randomly
      allocated to one of three groups: untreated control; IVM-CRC on Day 0; IVM-CRC on
      Day 84. For treatment an IVM-CRC for sheep weighing 20-45 kg was used which is
      designed to deliver ivermectin at a minimum dose of 20 microg/kg per day for 100
      days. The lambs were infested with 50-60 P. ovis mites each on Days 14 and 21.
      Mites in skin scrapings were counted on Days 70, 84, 98, 112 and 126. Body weight
      and feed consumption were measured every 2 weeks from Day 0 to 126. The animals
      were slaughtered on Day 127 and their carcasses evaluated. The IVM-CRC treatment
      on Day 0 prevented the establishment of P. ovis. All untreated lambs became
      infested. The lambs treated with an IVM-CRC on Day 84 became mite-free from Day
      112 onwards. The lambs treated on Day 0 had significantly (p<0.05) greater body
      weight gain from Day 0 to 84 (13.9 kg) and Day 0 to 126 (20.9 kg) than the
      untreated controls (9.6 and 12.8 kg, respectively) and the sheep treated on Day
      84 (8.4 and 14.9 kg, respectively). Feed consumption (Days 0-126) for sheep
      treated with the IVM-CRC on Day 0 was higher than for sheep treated on Day 84
      (p<0.05) and for the untreated controls (p<0.1). The carcasses of sheep treated
      with the IVM-CRC on Day 0 had significantly (p<0.05) higher warm and cold
      weights, carcass yield, rib eye area and back fat thickness than the untreated
      control group and the sheep treated with the IVM-CRC on Day 84. The sheep treated
      with the ivermectin CRC on either Day 0 or 84 had significantly (p<0.05) better
      muscle scores and lower muscle pH 1h post-slaughter than the untreated controls.
      There was no significant (p>0.1) difference between warm and cold carcass
      weights, carcass yield and rib eye area between sheep treated on Day 84 and
      untreated controls.

PMID- 10889364
TI  - Effects of Psoroptes ovis infection and its control with an ivermectin controlled
      release capsule on growing sheep. 2. Evaluation of wool production and leather
      value.
AB  - To evaluate the prophylactic and therapeutic effects of an ivermectin controlled
      release capsule (IVM-CRC) on the productivity of growing sheep infested with
      Psoroptes ovis 24 male and 24 female Merino landrace lambs, 5-6 months old and
      weighing 21.2-35.0 kg, were used. Sixteen replicates of three animals were formed
      based on sex and Day 0 body weight. Within each replicate animals were randomly
      allocated to one of three groups: untreated control; IVM-CRC on Day 0; IVM-CRC on
      Day 84. For treatment an IVM-CRC for sheep weighing 20-45 kg was used which is
      designed to deliver ivermectin at a minimum dose of 20 microg/kg/day for 100
      days. The lambs were infested with 50-60 P. ovis mites each on days 14 and 21.
      The animals were shorn on Day 126. After slaughter on Day 127 the quality of the
      leather produced from their skins was evaluated. The IVM-CRC treatment on Day 0
      prevented the establishment of P. ovis. All untreated lambs became infested. The
      lambs treated with an IVM-CRC on Day 84 became mite-free from Day 112 onwards.
      The lambs which were treated on Day 0 had significantly (p<0.05) greater clean
      fleece weight (1.5 kg) and fleece yield (52.1%) than the untreated controls (0.9
      kg and 34.1%, respectively) or than lambs treated on Day 84 (1.0 kg and 47.8%,
      respectively). Clean fleece weight and fleece yield were in the tendency
      (p=0.055) or significantly (p<0. 001) greater, respectively, for lambs treated on
      Day 84 than for the untreated controls. The chrome tanned dried crust leather of
      all untreated controls and six of the 16 lambs treated on Day 84 showed grain
      surface defects such as discolourations, indurations and coarse, pitted grain.
      The useful (defect-free) leather size was significantly (p<0.01) higher for the
      lambs treated on Day 0 (100%) than for the lambs treated on Day 84 (82.7%) and
      the untreated controls (7.8%). The physical testing revealed that the leather of
      sheep treated on Day 0 had significantly (p<0.05) higher thickness, elongation
      break and tear resistance than the leather of both untreated controls and sheep
      treated on Day 84. There were no significant differences in the physical
      characteristics of the leather of the untreated controls and the sheep treated on
      Day 84.

PMID- 10889365
TI  - In vitro effect of some anthelmintics on lactate dehydrogenase activity of
      Cotylophoron cotylophorum (Digenea: paramphistomidae).
AB  - Effects of praziquantel (PZQ), levamisole (LEV), mebendazole (MBZ), fenbendazole
      (FBZ) and albendazole (ABZ) on the lactate dehydrogenase (LDH) activity of
      Cotylophoron cotylophorum were studied in vitro. Maximum levels of inhibition of
      LDH catalysing both oxidation and reduction reactions were observed in PZQ- and
      LEV-treated worms. Similarly, benzimidazoles - MBZ, FBZ and ABZ - have also
      significantly inhibited the activity of LDH catalysing the oxidation of lactate;
      whereas the activity of LDH catalysing the reduction of pyruvate was accelerated.
      This affects the mitochondrial energy generating process which ultimately proves
      fatal to the parasite. Therefore, the mode of action of benzimidazoles is
      primarily on the activation of LDH catalysing the conversion of pyruvate to
      lactate.

PMID- 10889366
TI  - Use of a migration assay for the separation of adult pyrantel-susceptible and 
      resistant oesophagostomum dentatum.
AB  - A migration assay was used to separate a pyrantel-susceptible and -resistant
      isolate of the pig nematode, Oesophagostomum dentatum. The experiment had three
      steps. In the first step, LD(50) values for pyrantel of the two isolates in the
      assay were established. In the second step, susceptible and resistant worms were
      mixed in various proportions prior to exposure to a fixed concentration of
      pyrantel and thereafter assayed. The inhibition of migration showed to be
      linearly correlated with the proportion of resistant worms in a sample. In step
      three, this line was used as a standard curve to predict the number of resistant
      worms in samples from pigs infected with mixed samples of susceptible and
      resistant larvae.

PMID- 10889367
TI  - Evaluation of insecticide ear tags containing ethion for control of pyrethroid
      resistant Haematobia irritans (L.) on dairy cattle.
AB  - A field study was conducted in central Argentina to evaluate the efficacy of ear
      tags containing 36% ethion against pyrethroid resistant populations of Haematobia
      irritans on grazing dairy cattle. The treated group consisted of 45 milking
      Holstein cows which received two tags per head and the control consisted of 22
      dry cows from the same cohort. Treated and control groups were grazed on similar
      lucerne pastures separated for a minimum distance of 800 m but they were not
      isolated from other cattle herds on the same or contiguous properties. In both
      groups, horn fly estimation were made weekly by examining cattle in the pastures
      with the aid of binoculars. The percentage reduction of fly numbers on treated
      cows was considered as efficacy of control provided by the tags. The ethion ear
      tags provided a range of 85-99% reduction in horn fly numbers for 16 weeks.
      During this period, the weekly mean number of H. irritans on the tagged cows
      ranged between 0.44 and 28.26 compared with 143.5 and 239.1 in control animals.
      The ethion ear tags could be a useful tool for the control of H. irritans mainly
      in areas where populations of this insect have developed resistance to pyrethroid
      insecticides.

PMID- 10889368
TI  - Resistance of Fasciola hepatica against triclabendazole in cattle and sheep in
      The netherlands.
AB  - In the winter of 1998/1999, sheep on a farm in the province of North Holland, The
      Netherlands, died from subacute and chronic liver fluke disease despite four
      previous treatments with triclabendazole (TCBZ). Faecal examinations of sheep and
      cattle on the farm showed high number of liver fluke eggs. In a randomised
      clinical trial, the fluke egg output was monitored weekly for 3 weeks in sheep
      which were treated with TCBZ or with closantel; in dairy cows treated with TCBZ
      or with clorsulon; and in heifers treated with TCBZ or clorsulon. The results
      showed a significant reduction of 99.7, 98.1 and 99.2%, respectively, in fluke
      egg output at 21 days in all non-TCBZ treated animals. TCBZ treatment produced
      percentage decreases of 15.3, 4.3 and 36.6%, respectively. These results are
      highly indicative of the presence of TCBZ-resistant Fasciola hepatica in sheep
      and cattle on this farm.

PMID- 10889369
TI  - Cyclin D1 expression and early breast cancer recurrence following lumpectomy and
      radiation.
AB  - PURPOSE: The purpose of this study was to determine the prognostic significance
      of cyclin D1 (cycD1) levels in ipsilateral breast tumor recurrence (IBTR)
      following lumpectomy and radiation therapy. METHODS AND MATERIALS: A total of 98
      patients (49 patients with IBTR and 49 matched cases without IBTR) selected from
      our conservatively treated breast cancer population served as the patient
      population for the current study. All patients were treated with lumpectomy
      followed by radiation therapy to the intact breast to a total median dose of 64
      Gy. The patients were followed in our clinic with a median follow-up of 13 years.
      Immunohistochemical analysis of cycD1 in these 98 early-stage breast cancer
      patients was performed using a polyclonal antibody generated against the human
      cycD1 protein. All clinical, pathologic, and molecular variables were entered
      into a computerized data base for statistical analysis. RESULTS: Low levels of
      immunohistochemically detected cycD1 protein correlated with IBTR (p = 0.001),
      but there was no association between cycD1 protein levels and metastatic disease,
      axillary lymph node involvement, distant disease-free survival (DDFS), and
      overall survival (OS). Subgroup analysis revealed that for early breast tumor
      relapses (within 4 years of initial breast tumor diagnosis), low levels of cycD1
      were associated with IBTR (p = 0.004), but cycD1 expression was not prognostic
      for IBTR from breast cancer patients with late relapses (p = NS). CONCLUSION:
      These studies provide in vivo evidence for the prognostic and biologic
      significance of cycD1 expression in determining response to radiation therapy in
      breast cancer patients.

PMID- 10889370
TI  - Accuracy of the extent of axillary nodal positivity related to primary tumor
      size, number of involved nodes, and number of nodes examined.
AB  - PURPOSE: While a number of studies have evaluated the minimum number of axillary
      nodes that need to be examined to accurately determine nodal positivity or
      negativity, there is little information on the number of nodes which must be
      examined to determine the extent of nodal positivity. This study attempts to
      determine for patients with 1-3 positive nodes the probability that the number of
      positive nodes reported is the true number of positive nodes as well as the
      probability that 4 or more nodes could be positive based on primary tumor size
      and number of nodes examined. MATERIALS AND METHODS: From 1979 to 1998, 1652
      women with Stages I-II invasive breast cancer underwent an axillary dissection as
      part of their breast conservation therapy and had more than 10 lymph nodes
      examined. The mean and median number of nodes identified in the dissection was 19
      and 17 (range, 11-75). The median age was 55 years. A total of 1155 women had T1
      tumors and 497 had T2 tumors. Of the 459 node-positive women, 72% had 1-3
      positive nodes, 18% had 4-9 positive nodes, and 10% had 10 or more positive
      nodes. A mathematical model based on tumor size and number of nodes examined was
      created using the hypergeometric distribution and Bayes Theorem. The resulting
      model was used to estimate the accuracy of the reported number of positive nodes
      and the probability of 4 or more positive nodes based on various observed
      sampling combinations. RESULTS: For patients with T1 tumors and 1, 2, or 3
      positive nodes, the minimum number of nodes examined needed for a 90% probability
      of accuracy is 19, 20, and 20. For T2 tumors and 1, 2, or 3 positive nodes, a
      minimum of 20 nodes is required. The probability of 4 or more positive nodes
      increases as tumor size and the number of reported positive nodes increase and as
      the number of examined nodes decreases. For a 10% or less probability of 4 or
      more positive nodes, a patient with a T1 tumor and 1, 2, or 3 observed positive
      nodes would require a minimum of 8, 15, and 20 nodes removed. For a T2 tumor and
      1, 2, or 3 observed positive nodes, the corresponding numbers are 10, 16, and 20.
      CONCLUSION: The accuracy of the extent of axillary nodal positivity is influenced
      by the number of observed positive nodes, tumor size, and the number of nodes
      examined. Underestimation of the number of positive nodes will result in errors
      in the assessment of an individual's risk for locoregional recurrence, distant
      disease, and breast cancer death and will adversely impact on treatment
      recommendations. This model provides the clinician with a means for assessing the
      accuracy of the number of positive nodes reported in patients with 1-3 positive
      nodes.

PMID- 10889371
TI  - The acute effects of postoperative radiation therapy on the transverse rectus
      abdominis myocutaneous flap used in immediate breast reconstruction.
AB  - PURPOSE: To analyze the acute effects of postoperative radiation therapy on the
      transverse rectus abdominis myocutaneous (TRAM) flap reconstruction following
      modified radical mastectomy for breast cancer. METHODS AND MATERIALS: Twenty-five
      consecutive patients were treated with postoperative radiation therapy after TRAM
      flap reconstruction between 1985 and 1999. The radiation records for these
      patients were retrospectively reviewed. Information regarding treatment
      techniques, timing, and dose was obtained and correlated with the extent of
      erythema, desquamation, and the need for treatment break. RESULTS: The median age
      was 48 years. The median dose of chest wall radiation was 5040 cGy. Additional
      boost doses were delivered in 13 patients. Twelve patients (48%) developed mild
      erythema in the treatment field during the course of treatment and 13 patients
      (52%) developed moderate (40%) or brisk (12%) erythema. Only 10 patients (40%)
      developed any kind of desquamation; 5 patients (20%) developed dry desquamation
      and another 5 patients (20%) developed moist desquamation. No patients required a
      break in the course of treatment because of acute side effects. None of the
      parameters evaluated (the use of chemotherapy prior to radiation, the interval
      between surgery and radiation, smoking, prior incidence of fat necrosis, the use
      of bolus during radiation, and the use of a boost) were predictive of an
      increased incidence of either the extent of erythema or the development of
      desquamation in the treatment field. CONCLUSION: Postmastectomy radiation for
      TRAM flap reconstruction is well tolerated and is not associated with an
      increased incidence of acute side effects. Radiation technique and the use of
      preradiation chemotherapy do not appear to be correlated with an increased
      incidence of acute side effects.

PMID- 10889372
TI  - Locoregional irradiation for inflammatory breast cancer: effectiveness of dose
      escalation in decreasing recurrence.
AB  - PURPOSE: To evaluate the effect of radiation dose escalation on locoregional
      control, overall survival, and long-term complication in patients with
      inflammatory breast cancer. PATIENTS AND METHODS: From September 1977 to December
      1993, 115 patients with nonmetastatic inflammatory breast cancer were treated
      with curative intent at The University of Texas M. D. Anderson Cancer Center. The
      usual sequence of multimodal treatment consisted of induction FAC or FACVP
      chemotherapy, mastectomy (if the tumor was operable), further chemotherapy, and
      radiation therapy to the chest wall and draining lymphatics. Sixty-one patients
      treated from September 1977 to September 1985 received a maximal radiation dose
      of 60 Gy to the chest wall and 45-50 Gy to the regional lymph nodes, 22 treated
      once a day at 2 Gy per fraction, and 35 were treated b.i.d. (32 after mastectomy
      and all chemotherapy was completed, and 2 immediately after mastectomy; one
      patient had distant metastases discovered during b.i.d. irradiation, and
      treatment was stopped). Four additional patients received preoperative radiation
      with standard fractionation. Based on the analysis of the failure patterns of the
      patients, the dose was increased for the b.i.d. patients in the new series, with
      51 Gy delivered to the chest wall and regional nodes, followed by a 15-Gy boost
      to the chest wall with electrons. From January 1986 to December 1993, 39 patients
      were treated b.i.d. to this higher dose after mastectomy and all the chemotherapy
      was completed; and 8 additional patients received preoperative irradiation with
      b.i.d. fractionation to 51 Gy. During this period, another 7 patients were
      treated using standard daily doses of 2 Gy per fraction to a total of 60 Gy,
      either because they had a complete response or minimal residual disease at
      mastectomy or because their work schedule did not permit the b.i.d. regimen.
      Comparison was made between the groups for locoregional control, disease-free and
      overall survival, and complication rates. RESULTS: The median follow-up time was
      5.7 years (range, 1.8-17.6 years). For the entire patient group, the 5- and 10
      year local control rates were 73.2% and 67.1%, respectively. The 5- and 10-year
      disease-free survival rates were 32.0% and 28.8%, respectively, and the overall
      survival rates for the entire group were 40.5% and 31.3%, respectively. To
      evaluate the effectiveness of dose escalation, a specific comparison of patients
      who received b.i.d. radiation after mastectomy and completion of adjuvant
      chemotherapy was performed. There were 32 patients treated b.i.d. to 60 Gy in the
      old series versus 39 patients treated b.i.d. to 66 Gy in the new series. There
      was an significant improvement in the rate of locoregional control for the b.i.d.
      patients for the old vs. new series, from 57.8% to 84.3% and from 57.8% to 77.0%
      (p = 0.028) at 5 and 10 years, respectively. Chemotherapy regimens did not change
      significantly during this time period.Long-term complications of radiation, such
      as arm edema more than 3 cm (7 patients), rib fracture (10 patients), severe
      chest wall fibrosis (4 patients), and symptomatic pneumonitis (5 patients), were
      comparable in the two groups, indicating that the dose escalation did not result
      in increased morbidity. Significant differences in the rates of locoregional
      control (p = 0.03) and overall survival (p = 0.03), and a trend of better disease
      free survival (p = 0.06) were also observed that favored the recently treated
      patients receiving the higher doses of irradiation. CONCLUSION: Twice-daily
      postmastectomy radiation to a total of 66 Gy for patients with inflammatory
      breast cancer resulted in improved locoregional control, disease free survival,
      and overall survival, and was well tolerated.

PMID- 10889373
TI  - Changes in local pulmonary injury up to 48 months after irradiation for lymphoma
      and breast cancer.
AB  - PURPOSE: To assess the recovery from early local pulmonary injury after
      irradiation and to determine whether regional differences exist. METHODS: For 110
      patients treated for breast cancer or malignant lymphoma, single photon emission
      computed tomography (SPECT) perfusion and ventilation scans and CT scans were
      made before, 3, 18, and 48 months after radiotherapy. Dose-effect relations for
      changes in local perfusion, ventilation, and density were determined for each
      individual patient using spatially correlated SPECT and CT data sets, for each
      follow-up period. Average dose-effect relations for both subgroups were
      determined, as well as dose-effect relations for different regions. RESULTS: In
      general, partial improvement of local pulmonary injury was observed between 3 and
      18 months for each of the three endpoints. After 18 months, no further
      improvement was seen. Patients with breast cancer and malignant lymphoma showed a
      similar improvement (except for the perfusion parameter), which was attributed to
      a recovery from the early radiation response and could not be explained by
      contraction effects of fibrosis of lung parenchyma. No regional differences in
      radiosensitivity 18 months after treatment were observed, except for the dorsal
      versus ventral region. This difference was attributed to a gravity-related effect
      in the measuring procedure. CONCLUSION: For all patients, a partial recovery from
      early local perfusion, ventilation, and density changes, was seen between 3 and
      18 months after radiotherapy. After 18 months, local lung function did not
      further improve (lymphoma patients).

PMID- 10889374
TI  - Measuring radiation fibrosis: the interobserver reliability of two methods of
      determining the degree of radiation fibrosis.
AB  - PURPOSE: To compare the interobserver reliability of the palpation method with
      the method of measuring tissue compliance with a tissue compliance meter (TCM) on
      women who underwent breast-conserving surgery and radiotherapy for breast cancer.
      METHODS AND MATERIALS: Thirty-eight patients and 30 controls were measured with
      the palpation method by two radiation oncologists and with the TCM by two
      physiotherapists. Measurements were taken on four locations of the breasts of all
      68 women. Reliability coefficients were computed for both methods. A weighted
      kappa score was computed for the palpation method and this was compared with the
      intraclass correlation coefficient (ICC) computed for the TCM method. The
      conditions for direct comparison of these scores were met in this study. RESULTS:
      A weighted kappa of 0.65 was computed for the palpation method and an ICC of 0.91
      was computed for the TCM method. These scores differ significantly from each
      other (p < 0.01). CONCLUSION: The interobserver reliability of the TCM method is
      superior to that of the palpation method. However, at locations where the TCM is
      not applicable, palpation is a good alternative.

PMID- 10889375
TI  - A shorter fractionation schedule for postlumpectomy breast cancer patients.
AB  - PURPOSE: The purpose of this retrospective review was to determine the
      effectiveness of 40 Gy in 16 daily fractions in preventing local recurrence in
      postlumpectomy invasive breast cancer patients whose margins of resection were
      clear of tumor by at least 2 mm. METHODS: Between September 1989 and December
      1993, 294 breasts were treated with this regimen. The entire breast was treated,
      using a tangential parallel pair, with wedges as necessary, to a dose of 40 Gy in
      16 daily fractions. No additional boost was given. The median duration of follow
      up of surviving patients is 5.5 years. Recently, the patients' assessment of the
      cosmetic outcome of their treatment was obtained, using a mailed questionnaire.
      RESULTS: The 5-year actuarial breast-relapse rate was 3.5%, with an overall 5
      year survival and disease-specific survival of 87.8% and 92.1%, respectively. In
      response to the cosmesis questionnaire, 77% of patients stated they were either
      extremely or very satisfied with the overall appearance of the breast, 19.5%
      moderately satisfied, and 3.5% either slightly or not at all satisfied. The
      corresponding responses for overall level of comfort of the breast were 79%,
      16.5%, and 4.5% respectively. CONCLUSION: This regimen is very effective at
      preventing recurrent breast cancer in this group of patients, and it provides a
      high level of patient satisfaction with cosmetic outcome. Its short duration
      offers the added advantage of a more efficient use of resources and greater
      patient convenience.

PMID- 10889376
TI  - Progesterone receptor is a favorable prognostic factor of radiation therapy for
      adenocarcinoma of the uterine cervix.
AB  - PURPOSE: The prognostic significance of the expression of estrogen receptors (ER)
      and progesterone receptors (PgR) in adenocarcinoma of the uterine cervix has been
      controversial. Hence, the relationship between the expression of the hormone
      receptors and clinical outcome was evaluated for patients with adenocarcinoma
      treated with radiation therapy alone. MATERIALS AND METHODS: This study involved
      66 patients with cervical adenocarcinoma consisting of 44 adenocarcinomas and 22
      adeno-squamous cell carcinomas. They received radiation therapy at the National
      Institute of Radiological Sciences Hospital between 1962 and 1993. The mean age
      of the patients was 62. 0 +/- 12.0 years (range, 36-82 years). The numbers of
      patients with Stage I, II, III, and IV diseases were 7, 17, 27, and 15,
      respectively. Their ER and PgR statuses were investigated immunohistochemically
      using biopsy specimens excised from the cervical tumors before radiation therapy.
      RESULTS: ER staining was positive in 12 patients (19%). ER status did not
      correlate with the 5-year cause-specific, local-control, and disease-free
      survivals. PgR staining was positive in 12 patients (19%). The disease-free
      survival rate of PgR-positive patients was significantly higher than that of PgR
      negative patients (p = 0.044). Although PgR status did not reach statistical
      significance in relation to the 5-year cause-specific survival and local-control
      survival, the better survival was due to less local recurrence rather than to
      less distant metastasis. CONCLUSION: The present study suggested that PgR status
      was associated with prognosis after radiation therapy for adenocarcinoma of the
      uterine cervix.

PMID- 10889377
TI  - Chemoradiation as primary or adjuvant treatment for locally advanced carcinoma of
      the vulva.
AB  - PURPOSE: To determine the impact of primary or adjuvant chemotherapy and
      radiation (CRT) on the survival rates of patients with locally advanced vulvar
      carcinoma. METHODS AND MATERIALS: Between 1973 and 1998, 54 patients with vulvar
      cancer were treated with radiation therapy, among which 20 received CRT, while 34
      patients received radiation therapy (RT) alone. Of the 20 patients, 14 were
      treated for primary or recurrent disease (pCRT), and 6 after radical vulvectomy
      for high-risk disease (aCRT). Of the 34 patients, 12 were treated primarily (pRT)
      and 22 received adjuvant treatment (aRT). Chemotherapy consisted of 2 courses of
      5-fluorouracil (5-FU) and mitomycin C administered during RT. Six patients
      received cisplatin in place of mitomycin C. In CRT groups, radiation was
      administered to the vulva, pelvic, and inguinal lymph nodes to a median dose of
      45 Gy with additional 6-17 Gy to gross disease. In RT groups, the median dose to
      the microscopic diseases was 45 Gy. Nine patients received external beam boost
      and 16 patients received supplementary brachytherapy in the forms of (226)Ra or
      (241)Am plaques to sites of macroscopic disease. RESULTS: Overall survival was
      superior in the patients treated with pCRT versus pRT with statistical
      significance (p = 0.04). There was also a statistically significant improvement
      in disease-specific (p = 0.03) and relapse-free survival (p = 0.01) favoring
      pCRT. No statistically significant trends of improved survival rates favoring
      aCRT over aRT were observed. CONCLUSION: Concurrent radiation therapy and
      chemotherapy decreases local relapse rate, improves disease-specific and overall
      survival over RT alone as primary treatment for locally advanced vulvar cancer.

PMID- 10889378
TI  - Analysis of biopsy outcome after three-dimensional conformal radiation therapy of
      prostate cancer using dose-distribution variables and tumor control probability
      models.
AB  - PURPOSE: To investigate tumor control following three-dimensional conformal
      radiation therapy (3D-CRT) of prostate cancer and to identify dose-distribution
      variables that correlate with local control assessed through posttreatment
      prostate biopsies. METHODS AND MATERIAL: Data from 132 patients, treated at
      Memorial Sloan-Kettering Cancer Center (MSKCC), who had a prostate biopsy 2.5
      years or more after 3D-CRT for T1c-T3 prostate cancer with prescription doses of
      64.8-81 Gy were analyzed. Variables derived from the dose distribution in the PTV
      included: minimum dose (Dmin), maximum dose (Dmax), mean dose (Dmean), dose to n%
      of the PTV (Dn), where n = 1%,...,99%. The concept of the equivalent uniform dose
      (EUD) was evaluated for different values of the surviving fraction at 2 Gy
      (SF(2)). Four tumor control probability (TCP) models (one phenomenologic model
      using a logistic function and three Poisson cell kill models) were investigated
      using two sets of input parameters, one for low and one for high T-stage tumors.
      Application of both sets to all patients was also investigated. In addition,
      several tumor-related prognostic variables were examined (including T-stage,
      Gleason score). Univariate and multivariate logistic regression analyses were
      performed. The ability of the logistic regression models (univariate and
      multivariate) to predict the biopsy result correctly was tested by performing
      cross-validation analyses and evaluating the results in terms of receiver
      operating characteristic (ROC) curves. RESULTS: In univariate analysis,
      prescription dose (Dprescr), Dmax, Dmean, dose to n% of the PTV with n of 70% or
      less correlate with outcome (p < 0.01). The area under the ROC curve for Dmean is
      0.64. In contrast, Dmin (p = 0.6), D98 (p = 0.2) or D95 (p = 0.1) are not
      significantly correlated with outcome. The results for EUD depend on the input
      parameter SF(2): EUD correlates significantly with outcome for SF(2) of 0.4 or
      more, but not for lower SF(2) values. Using either of the two input parameters
      sets, all TCP models correlate with outcome (p < 0.05; ROC areas 0.60-0.62).
      Using T-stage dependent input parameters, the correlation is improved (logistic
      function: p < 0.01, ROC area 0.67, Poisson models: p < 0.01, ROC areas 0.64
      0.66). In comparison, the ROC area is 0.68 for the combination of Dmean and T
      stage. After multivariate analysis, a model based on TCP, D20 and Gleason score
      is the best overall model (ROC area 0.73). However, an alternative model based on
      Dmean, Gleason score, and T-stage is competitive (ROC area 0.70). CONCLUSION:
      Biopsy outcome after 3D-CRT of prostate cancer at MSKCC is not correlated with
      Dmin in the PTV and appears to be insensitive to cold spots in the dose
      distribution. This observation likely reflects the fact that much of the PTV,
      especially at the periphery, may not contain viable tumor cells and that the
      treatment margins were sufficiently large. Therefore, the predictive power of all
      variables which are sensitive to cold spots, like TCPs with Poisson models and
      EUD for low SF(2), is limited because the low dose region may not coincide with
      the tumor location. Instead, for MSKCC prostate cancer patients with their
      standardized CTV definition, substantial target motion and small dose
      inhomogeneities, Dmean (or any variable that downplays the effect of cold spots)
      is a very good predictor of biopsy outcome. While our findings may indicate a
      general problem in the application of current TCP models to clinical data, these
      conclusions should not be extrapolated to other disease sites without careful
      analysis.

PMID- 10889379
TI  - Five-year biochemical outcome and toxicity with transperineal CT-planned
      permanent I-125 prostate implantation for patients with localized prostate
      cancer.
AB  - PURPOSE: To report the 5-year prostate-specific antigen (PSA) relapse-free
      survival outcome and incidence of long-term morbidity for patients with localized
      prostate cancer treated with CT-planned permanent I-125 prostate implantation
      using a transperineal technique (TPI). METHODS AND MATERIALS: Between 1989-1996,
      248 patients with clinically localized prostate cancer were treated with TPI. The
      median age was 65 years (range: 45-80 years). The clinical stage was T1c in 143
      patients (58%), Stage T2a in 102 (41%), and T2b in 3 (1%). Thirty patients (12%)
      had Gleason scores <6, 158 patients (64%) had Gleason scores of 6, and 60 (24%)
      had scores >or =7. The median pretreatment PSA was 7 ng/mL (range: 1-58 ng/mL).
      The median prescribed implant dose was 150 Gy. Patients were characterized as
      having favorable risk disease if their pretreatment PSA level was < or =10.0
      ng/mL and Gleason score < or = 6; those with one and two adverse prognostic
      features (PSA > 10 ng/mL and Gleason score >6) were classified as having
      intermediate and unfavorable risk disease, respectively. PSA relapse was defined
      according to the American Society of Therapeutic Radiation Oncology Consensus
      Statement, and toxicity was scored according to the Radiation Therapy Oncology
      Group morbidity scoring scale. The median follow-up was 48 months (range: 12-126
      months). RESULTS: Thirty-eight patients (15%) developed a PSA relapse, and the
      overall 5-year PSA relapse-free survival (PRFS) rate was 71%. The 5-year PRFS
      rates for favorable-risk (n = 146), intermediate-risk (n = 85), and unfavorable
      risk (n = 17) patients were 88%, 77%, and 38%, respectively (p < 0.0001). The 5
      year PRFS rates among patients treated with a 2-month course of neoadjuvant
      androgen deprivation (NAAD) prior to TPI compared to patients treated with TPI
      only were 100% and 77%, respectively (p = 0.03). Multivariate analysis identified
      pretreatment PSA > 10 ng/mL and Gleason score >6 as independent predictors for
      biochemical relapse after TPI. The 5-year actuarial likelihood of late Grade 2
      urinary toxicity was 41%. The 5-year likelihood of urethral stricture development
      was 10%, and the median time to stricture development was 18 months. One patient
      (0. 4%) in the early phase of this clinical experience developed a Grade 4
      urethral complication. The actuarial incidence of late Grade 2 rectal bleeding
      was 9%. One patient (0.4%) developed a Grade 4 rectal complication. CONCLUSIONS:
      Especially for favorable risk disease, the 5-year biochemical outcome with this
      approach was excellent and appears to be comparable to other therapeutic
      interventions. Grade 2 urinary symptoms were common in these patients but
      gradually resolved in most. Improved treatment planning approaches that further
      constrain the urethral dose without compromising the target volume dose will
      likely decrease the incidence of Grade 2 and 3 urinary symptoms after TPI.

PMID- 10889380
TI  - Long-term results with radiation therapy for pediatric desmoid tumors.
AB  - PURPOSE: To retrospectively review the treatment and outcome of pediatric
      patients with desmoid tumor who received radiation therapy at a single
      institution. MATERIALS AND METHODS: Thirteen pediatric patients received
      radiation therapy for desmoid tumor at St. Jude Children's Research Hospital
      between 1962 and 1998. Only 2 of the patients reviewed received treatment prior
      to 1976. The median dose of external beam irradiation was 50 Gy. RESULTS: At the
      time of this report, 10 of 13 patients have had tumors that recurred after
      radiation therapy and 3 have died from their disease. One additional patient was
      harboring a recurrence, and 1 had not been followed long enough to suggest that
      the patient had achieved disease control. One patient remained locally controlled
      after radiation therapy with long-term follow-up (196 months). The median time to
      recurrence following radiation therapy was 19 months (range, 3-135 months). Eight
      of the 13 patients suffered substantial tumor and treatment-related morbidity.
      CONCLUSIONS: Desmoid tumors in pediatric patients are locally aggressive tumors
      that are likely to recur after radiation therapy. Alternatives to radiation
      therapy should be sought for the treatment of these tumors, and efforts should
      focus on low-morbidity therapies aimed at inhibiting the growth of these unique
      tumors.

PMID- 10889381
TI  - Morbidity of adjuvant brachytherapy in soft tissue sarcoma of the extremity and
      superficial trunk.
AB  - PURPOSE: We have previously shown that adjuvant brachytherapy (BRT) improves
      local control in soft tissue sarcoma (STS) of the extremity and superficial
      trunk. A detailed assessment of the morbidity of this approach has not been
      examined. The purpose of this study was to evaluate the toxicity associated with
      adjuvant BRT in terms of wound complications, bone fracture, and peripheral nerve
      damage. METHODS AND MATERIALS: Between July 1982 and June 1992, 164 adult
      patients with STS of the extremity or superficial trunk were randomized
      intraoperatively to receive or not to receive BRT after complete resection. BRT
      was delivered with (192)Ir to a total dose of 42-45 Gy. The BRT and no-BRT arms
      were balanced with regard to age, sex, presentation (primary vs. recurrent),
      site, grade, size, and depth. Morbidity was assessed in terms of significant
      wound complication, bone fracture, and peripheral nerve damage (grade > or = 3).
      The significant wound complications were defined as those wound problems
      requiring operative revision for coverage or threatened limb loss, persistent
      seroma requiring repeated aspirations and/or drainage, wound separation > 2 cm,
      hematoma > 25 ml, and/or purulent wound discharge. The median follow-up was 100
      months. RESULTS: The significant wound complication rate was 24% in the BRT group
      and 14% in the no-BRT group, (p = 0.13). The rate of wound reoperation, however,
      was significantly higher in the BRT arm (10% vs. 0%; p = 0. 006). Examination of
      other covariables that may have contributed to wound reoperation revealed the
      width of the excised skin (WES) to be a significant factor [1% (WES < or = 4 cm)
      vs. 10% (WES > 4 cm), p = 0. 02]. Bone fracture only occurred in patients
      receiving BRT (n = 3, 4%), although this was not statistically significant (p =
      0.2). The rate of peripheral nerve damage, however, was similar in both arms (7%
      vs. 7%). CONCLUSION: The overall morbidity associated with adjuvant BRT was not
      significantly higher than that with surgery alone. However, BRT and WES > 4 cm
      were associated with significantly higher wound reoperation rate. This has
      significant implications for strategies designed to maximize wound coverage in
      patients who receive BRT.

PMID- 10889382
TI  - The outcome of combined-modality treatments for stage I and II primary large B
      cell lymphoma of the mediastinum.
AB  - PURPOSE: Primary mediastinal large B-cell lymphoma (PML) has clinicopathologic
      features distinct from those of other diffuse large-cell lymphomas. However, the
      optimal treatment for this tumor is evolving, and in particular, the role of
      radiation therapy remains undefined. We conducted a retrospective review to
      evaluate the role of radiation therapy in this disease. METHODS AND MATERIALS:
      The medical records of 40 consecutive patients with Ann Arbor Stage I or II PML
      treated at our institution from January 1980 to December 1995 were reviewed.
      There were 18 patients with Stage I disease and 22 patients with Stage II
      disease; 62.5% were women and 37.5% were men. The median age was 32.4 years
      (range, 17-74 years). The tumor scores were 0 in 1 patient, I in 5 patients, II
      in 13 patients, III in 7 patients, IV in 4 patients, and unknown in 10 patients.
      The International Prognostic Index (IPI) was 0 in 10 patients, I in 26 patients,
      II in 2 patients, and unknown in 2 patients. All patients were treated with
      doxorubicin-based chemotherapy, and 35 patients received radiation therapy. For
      most patients who received radiation therapy, an involved field or a modified
      mantle field was used, and a dose of 40 Gy in 20 fractions or 39.6 Gy in 22
      fractions was administered. Univariate analysis was performed to identify
      prognostic factors. RESULTS: The median follow-up in surviving patients was 56
      months (range, 19-194 months). The actuarial 5-year relapse-free survival (RFS)
      rate and overall survival (OS) rate for all patients were 67% and 72%,
      respectively. Thirty-five patients achieved a complete response; 32 of these
      patients received radiation therapy. The patterns of failure for the complete
      responders were as follows: locoregional failure alone for 1 patient (at the
      margin of the radiation field); distant failure alone for 5 patients; and both
      locoregional (in-field) and distant failure for 1 patient. There were no failures
      after 2.5 years. None of the 5 patients who never achieved a complete response
      had local control, and all died with disease. Only 2 of the 5 completed the
      planned course of radiation therapy; both had massive mediastinal disease. There
      was no treatment-related death from the initial chemotherapy or radiation
      therapy. One patient developed a second malignancy (sarcoma) within the radiation
      field after 13 years. The tumor score was a significant predictor of RFS (p =
      0.016) and OS (p = 0.006), but the IPI did not prove to be a significant
      predictor. CONCLUSION: We recommend consolidative radiation therapy in view of
      the excellent local control and the lack of significant toxicity. Modified mantle
      or involved field appears to be an adequate volume, and 39.6-40 Gy appears to be
      an adequate dose. The tumor score is a significant prognostic factor.

PMID- 10889383
TI  - The influence of the radicality of resection and dose of postoperative radiation
      therapy on local control and survival in carcinomas of the upper aerodigestive
      tract.
AB  - PURPOSE: To evaluate dose concepts in postoperative irradiation of carcinomas of
      the upper aerodigestive tract according to the radicality of resection. PATIENTS
      AND METHODS: In a retrospective analysis, the charts of 257 patients with
      histologically-proven carcinoma of the upper aerodigestive tract (40 T1, 80 T2,
      53 T3, 84 T4 tumors, with nodal involvement in 181 cases) were reviewed according
      to the radicality of resection and dose of irradiation administered. Sixty-four
      patients had tumor-free resection margins (> 3 mm), 66 patients had close
      resection margins (< 3 mm), and 101 patients had R1 resections, and 26 patients
      had R2 resections. A median dose of 56 Gy was applied to the primary tumor bed
      and the cervical lymphatics (2 Gy/fraction, 5 fractions/week). In cases of R1 or
      R2 resection, or of close margins (< 3 mm), the tumor bed or, respectively, tumor
      residuals were boosted with doses up to a median of 66 Gy. Locoregional tumor
      control and survival was investigated by uni- and multivariate analyses according
      to T-, N-stage, grade of resection, total dose of radiation, and presence or
      absence of extracapsular tumor spread and lymphangiosis carcinomatosa. RESULTS:
      An overall 3- and 5-year survival rate of 60% and 45%, respectively, was
      achieved. Rates for freedom from locoregional recurrence were 77% and 72% at 3
      and 5 years, respectively. The survival rates according to the grade of resection
      at 5 years were 67% for patients resected with tumor-free margins, 59% for
      patients resected with close margins, 26% for patients with R1 resection, and 27%
      for patients with R2 resection. Within a median follow-up period of 4.7 years for
      living patients, a total of 67 recurrences (26%) were observed (in 9% of patients
      resected with tumor-free margins, in 27% with close margins, in 37% of R1
      resected, and in 19% of R2 resected patients). Freedom from locoregional
      recurrence at 3 years was achieved in 100% of the patients resected with tumor
      free margins, in 92% of patients resected with close surgical margins, in 87% of
      R1 and 69% of R2 resected patients. In multivariate Cox-regression analysis, the
      variables grade of resection (p = 0.00031) and total dose of irradiation (p =
      0.0046) were found as factors influencing locoregional control. Variables
      influencing survival according to multivariate analysis are T-stage (p = 0.0057),
      N-stage (p = 0.024), grade of resection (p = 0.000015), total dose of irradiation
      (p < 0. 000000). Extracapsular tumor spread and lymphangiosis carcinomatosa are
      factors of borderline significance (p = 0.055, p = 0.066). CONCLUSION: In
      postoperative radiotherapy of head and neck carcinomas, doses adapted to the risk
      of locoregional recurrent disease should be applied. Patients with R1 and R2
      resections should be treated with doses of more than 68 Gy (2 Gy/fraction, 5
      fractions/week) (with close margins [< 3 mm] more than 66 Gy) to achieve an
      improvement in locoregional control and survival.

PMID- 10889384
TI  - Beam intensity modulation using tissue compensators or dynamic multileaf
      collimation in three-dimensional conformal radiotherapy of primary cancers of the
      oropharynx and larynx, including the elective neck.
AB  - INTRODUCTION: The treatment of midline tumors in the head and neck by
      conventional radiotherapy almost invariably results in xerostomia. This study
      analyzes whether a simple three-dimensional conformal radiotherapy (3D-CRT)
      technique with beam intensity modulation (BIM) (using a 10-MV beam of the MM50
      Racetrack Microtron) can spare parotid and submandibular glands without
      compromising the dose distribution in the planning target volume (PTV). METHODS:
      For 15 T2 tumors of the tonsillar fossa with extension into the soft palate (To)
      and 15 T3 tumors of the supraglottic larynx (SgL), conventional treatment plans,
      consisting of lateral parallel opposed beams, were used for irradiation of both
      the primary tumor (70 Gy) and the elective neck regions (46 Gy). Separately, for
      each tumor a 3-D conformal treatment plan was developed using the 3-D computer
      planning system, CadPlan, and Optimize, a noncommercial program to compute
      optimal beam profiles. Beam angles were selected with the intention of optimal
      sparing of the salivary glands. The intensity of the beams was then modulated to
      achieve a homogeneous dose distribution in the target for the given 3D-CRT
      techniques. The dose distributions, dose-volume histograms (DVHs) of target and
      salivary glands, tumor control probabilities (TCPs), salivary gland volumes
      absorbing a biologically equivalent dose of greater than 40 or 50 Gy, and normal
      tissue complication probabilities (NTCPs) of each treatment plan were computed.
      The parameters of the 3D-CRT plans were compared with those of the conventional
      plans. RESULTS: In comparison with the conventional technique, the dose
      homogeneity in the target volume was improved by the conformal technique for both
      tumor sites. In addition, for the SgL conformal technique, the average volumes of
      the parotid glands absorbing a BED of greater than 40 Gy (V40) decreased by 23%,
      and of the submandibular glands by 7% (V40) and 6% (V50). Consequently, the
      average NTCPs for the parotid and submandibular glands were reduced by 7% and 6%,
      respectively. For the To conformal techniques, the V40 of the parotid glands was
      decreased on average by 31%, resulting in an average reduction of the NTCP by
      49%. Both the average V50 and the NTCP of the submandibular glands were decreased
      by 7%. CONCLUSION: For primary tumors of the oropharynx, the parotid glands could
      be spared to a considerable degree with the 3D-CRT technique. However,
      particularly the ipsilateral submandibular gland could not be spared. For primary
      tumors of the larynx, the 3D-CRT technique allows sparing of all salivary glands
      to a considerable and probably clinically relevant degree. Moreover, the
      conformal techniques resulted in an increased dose homogeneity in the PTV of both
      tumor sites.

PMID- 10889385
TI  - Brachytherapy for primary and recurrent nasopharyngeal carcinoma: 20 years'
      experience at Long Beach Memorial.
AB  - PURPOSE: We evaluated treatment outcomes of patients with mostly locally advanced
      primary and recurrent cancer of the nasopharynx managed with interstitial and
      intraluminal brachytherapy. METHODS AND MATERIALS: This is a retrospective
      analysis of 56 patients with cancer arising from the nasopharynx treated with
      interstitial and intracavitary afterloading brachytherapy from 1978 to 1997.
      Patients were divided into three treatment groups: 15 patients with primary
      cancer (Group 1), 34 patients with recurrent or persistent disease (Group 2), and
      7 patients with cancer in the nasopharynx who had history of previous definitive
      radiation therapy to the nasopharynx for head and neck cancer (Group 3). Fifty
      three percent of patients in Group 1 had 1992 AJCC Stage IV disease, and 49% of
      patients in Groups 2 and 3 had extensive disease (defined as T3, T4, or
      parapharyngeal extension). Group 1 received megavoltage radiation to 50-60 Gy
      followed by a boost to the primary site and neck (in cases of persistent neck
      disease) with a combination of interstitial and intracavitary brachytherapy (mean
      dose 33-37 Gy). Five patients received chemotherapy, and 6 patients received
      hyperthermia. Groups 2 and 3 patients were treated with brachytherapy implants
      (mean dose 50-58 Gy) without external beam radiation. Twenty-five patients
      received chemotherapy either before or during radiation, and 21 patients received
      hyperthermia. RESULTS: The overall survival at 2, 5, and 10 years for patients in
      Group 1 was 79%, 61%, and 61%, respectively, and for patients in Groups 2 and 3
      combined was 48%, 30%, and 20%, respectively. Cause-specific survival at 2, 5,
      and 10 years was 87%, 74%, and 74%, respectively, for patients in Group 1; and
      82%, 60%, and 60%, respectively, for patients in Groups 2 and 3. Local control at
      2, 5, and 10 years was 93%, 93%, and 77%, respectively, for patients in Group 1;
      and 81%, 59%, and 49%, respectively, for patients in Groups 2 and 3. Control in
      the neck at 2, 5, and 10 years was achieved in 93%, 93%, and 93% of patients,
      respectively, in Group 1; and 88%, 81%, and 81%, respectively, for patients in
      Groups 2 and 3. Disease-free survival was 87%, 74%, and 62%, respectively, for
      patients in Group 1, and 56%, 41%, and 34%, respectively, for patients in Groups
      2 and 3. There were 4 peri-operative deaths. One death (2%) was attributable to
      the development of late complications. Forty-five percent of patients experienced
      some form of late complications. CONCLUSION: Interstitial afterloading
      brachytherapy can provide effective treatment for nasopharyngeal cancers,
      especially for locally persistent/recurrent and locally extensive lesions.

PMID- 10889386
TI  - Reconstruction and navigation system for intraoperative brachytherapy using the
      flab technique for colorectal tumor bed irradiation.
AB  - PURPOSE: To present the development of a new navigation and reconstruction system
      based on an electromagnetic free-hand tracker and on CT imaging for treatment
      planning of intraoperative high-dose-rate brachytherapy (IORT-HDRB) in the sacral
      region. Our aim is to improve accuracy and to enable individualized treatment
      planning and dose documentation to be performed for IORT-HDRB using a flab
      technique. METHODS AND MATERIALS: The material consists of an electromagnetic 3D
      tracker system, a PC workstation with Microsoft Windows NT 4.0 operating system,
      and a recognition program for continuous speech. In addition, we designed an
      external reference system constructed of titanium and Perspex, which is
      positioned in the pelvis, and a special digitizer pen for reconstruction of the
      flab geometry. The flab design incorporates a series of silicon 10-mm-diameter
      spherical pellets. Measurements were made with a pelvic phantom in order to study
      the accuracy of the system. The reconstruction results are stored and can be
      exported via network or floppy to our different treatment planning systems.
      RESULTS: Our results for the reconstruction of a flab with six catheters and a
      total of 100 spherical pellets give mean errors in the range (2.5 +/- 0.6) mm to
      (3.5 +/- 0.8) mm depending on the positions of the pelvic phantom and transmitter
      relative to the operation table. These errors are calculated by comparing the
      reconstruction results of our system with those using a CT-based reconstruction
      of the flab geometry. For the accuracy of the navigation system for the pelvic
      phantom, we obtained mean errors in the range (2.2 +/- 0.7) mm to (3. 1 +/- 1.0)
      mm. CONCLUSIONS: The new system we have developed enables navigation and
      reconstruction within the surgical environment with a clinically acceptable level
      of accuracy. It offers the possibility of individualized treatment planning and
      effective documentation of the 3D dose distribution in IORT-HDRB using a flab
      technique.

PMID- 10889387
TI  - Local radiotherapy for unresectable hepatocellular carcinoma patients who failed
      with transcatheter arterial chemoembolization.
AB  - PURPOSE: The purpose of this study was to investigate the efficacy of local
      radiotherapy (RT) as a salvage treatment for unresectable hepatocellular
      carcinoma (HCC) patients who failed with transcatheter arterial chemoembolization
      (TACE). METHODS AND MATERIALS: Patients with unresectable HCC who had been
      treated with and eventually failed with TACE were eligible. The judgment of TACE
      failure was based on incomplete tumor filling of lipiodol-adriamycin mixture on
      either angiography or computed tomography (CT) scan. From January 1993 to
      December 1997, 27 patients were entered into this study. They had UICC Stage III
      (17) or IVA (10) disease, with a mean tumor size of 7.2 +/- 2.9 cm. Local RT was
      done, with a mean tumor dose of 51.8 +/- 7.9 Gy, in daily 1.8-Gy fractions using
      a 10- or 6-MV linear accelerator. Survival was calculated from both the diagnosis
      and the start of RT using the Kaplan-Meier method. RESULTS: An objective response
      was observed in 16 of 24 patients (66.7%) including 1 CR. Intrahepatic metastasis
      was noted outside the RT field in 10 patients (37.0%). Extrahepatic distant
      metastasis occurred in 4 patients. Survival rates at 1, 2, and 3 years were 85.
      2%, 58.1%, and 33.2%, respectively, from the diagnosis and 55.9%, 35. 7%, and
      21.4%, respectively, from the start of RT. The median survivals were 26 months
      from the diagnosis and 14 months from the start of RT. Acute toxicity involved
      alteration in liver function test (13 patients) and thrombocytopenia (2
      patients). Subacute and chronic toxicity involved gastroduodenal ulcer (3
      patients) and duodenitis (2 patients). There was no treatment-related death.
      CONCLUSION: In unresectable HCC patients who failed with TACE, local RT induced a
      substantial tumor response of 66.7%, with a 3-year survival rate of 21.4% and a
      median survival time of 14 months. Toxicity was significant but manageable.
      Although we do not know if there is survival benefit through this treatment,
      local RT in these patients seems to be valuable as a salvage for TACE-failed HCC.

PMID- 10889388
TI  - The efficacy of conventional radiation therapy in the management of pituitary
      adenoma.
AB  - PURPOSE: To evaluate the efficacy of conventional radiotherapy for reducing tumor
      size and endocrine hypersecretion of pituitary adenomas. METHODS AND MATERIALS:
      We reviewed the records of 91 patients with pituitary adenoma, who were first
      treated between 1969 and 1994 and had been followed for more than 2 years
      (median, 8.2 years.) Of these patients, 86 had received postoperative
      radiotherapy, and 5 had received radiotherapy alone. The median total dose was 51
      Gy. Clinical symptoms related to mass effects or endocrine hypersecretion were
      assessed. The efficacy of radiotherapy was evaluated before treatment and during
      the follow-up period (1-14 years; median, 3 years) by estimating tumor size on
      computed tomography or magnetic resonance imaging in 56 patients, as well as by
      endocrine testing in the 22 patients who had secreting adenomas. Local control
      rate, prognostic factors, and side effects were analyzed. RESULTS: Mass-effect
      symptoms improved in 72% and 79% of patients who had such symptoms due to
      nonsecreting adenomas and secreting adenomas, respectively. Symptoms of endocrine
      hypersecretion abated in 67% of patients who had such symptoms. Excessive hormone
      levels normalized in 74% of patients who showed endocrine hypersecretions. The
      greatest size reduction was seen 3 years after the completion of radiotherapy
      (24% CR, 62% PR, 12% NC, and 3% PD in nonsecreting adenomas, and 32% CR, 36% PR,
      27% NC, and 5% PD in secreting adenomas). Three patients with secreting adenomas
      (2 with prolactinoma and 1 with Cushing's disease) showed a mismatch between
      reduction in tumor size and normalization of endocrine hypersecretion. The 10
      year local control rates were 98%, 85%, 83%, and 67% for nonsecreting adenoma,
      growth-hormone-secreting adenoma, prolactinoma, and Cushing's disease,
      respectively. Univariate analyses showed that disease type and radiation field
      size were significant prognostic factors. Brain necrosis occurred in 1 patient
      who received a 60-Gy dose of irradiation. CONCLUSION: We conclude that
      conventional external radiotherapy with 50 Gy is safe and sufficient to control
      pituitary adenoma. Careful observation is required in the management of secreting
      adenomas because the effects on tumor size and endocrine hypersecretion may be
      mismatched in some secreting adenomas.

PMID- 10889389
TI  - A prospective evaluation of the timing of postoperative radiotherapy for
      preventing heterotopic ossification following traumatic acetabular fractures.
AB  - PURPOSE: Preoperative and immediate postoperative irradiation of traumatic
      acetabular fractures (TAF), although known to reduce heterotopic ossification
      (HO), can cause significant organizational and logistic difficulties. We sought
      to determine an acceptable time interval between surgery and radiation without
      compromising control, as well as to update our large experience and to further
      validate our treatment philosophy. METHODS AND MATERIALS: Beginning in June 1995,
      we began a prospective study, irradiating 152 patients on postoperative days 1,
      2, or 3. There were also 17 patients delayed further secondary to medical
      difficulties. RESULTS: All patients treated since June 1995 received 700 cGy/1
      fx. Fifty-eight patients received radiation within 24 hours of surgery, 41 within
      2 days, 53 within 3 days, 13 within 4 days, and 4 were delayed further. Delaying
      irradiation for up to 4 days postoperatively caused no statistical increase in HO
      (p = 0.625). Of 263 patients in our retrospective cohort, HO occurred in 5.3% of
      patients who received irradiation versus 60% of patients who did not. CONCLUSION:
      In our prospective study, we noted no perceptible increase in HO with up to a 3
      day interval between surgery and radiotherapy. This allows a more structured
      treatment schedule and allows the patient more time to heal and recover. Updated
      results from our overall series continue to demonstrate that adjuvant radiation
      decreases the incidence and severity of HO after TAF.

PMID- 10889390
TI  - Low-dose radiotherapy in 179 patients with Peyronie's disease: treatment outcome
      and current sexual functioning.
AB  - PURPOSE: To analyse retrospectively treatment outcome in patients irradiated for
      Peyronie's disease. METHODS AND MATERIALS: The records of 179 patients, median
      age 52 years, that received radiotherapy (RT) between 1982 and 1997 were
      reviewed. 78% presented with painful erections and 89% with penile deformity. The
      symptoms were present for a median duration of 6 months (range, 1-72 months). The
      RT schedule consisted of 13.5 Gy (9 x 1.5 Gy, 3 fractions per week) using
      orthovoltage X-rays in 123 patients or 12 Gy (6 x 2 Gy, daily fractions) using
      electrons in 56 patients. A questionnaire regarding current sexual functioning
      was mailed to 130 patients whose addresses could be traced; 106 (82%) responded.
      RESULTS: At mean follow-up period of 3 months, 83% reported that pain was
      diminished or had disappeared after RT. Twenty-three percent of patients reported
      a decrease in penile deformity. Following RT, surgical correction of penile
      curvature was performed in 29% of patients. No RT-related complications occurred
      except transient dysuria in 1 patient. Questionnaire data: 72% of patients were
      currently sexually active, 48% had erectile dysfunction, and 49% expressed
      dissatisfaction with their current sexual functioning. CONCLUSION: Low-dose
      external RT (12-13.5 Gy) results in relief of pain in the majority of patients
      with Peyronie's disease. Improvement in penile deformity was observed, avoiding
      surgery in a number of patients. No significant RT-associated morbidity was
      encountered. It is disappointing that almost 50% of patients complain of sexual
      functioning, but this is presumably not related to radiotherapy.

PMID- 10889391
TI  - The Harvard Joint Center for Radiation Therapy, 1968-1999: a unique concept and
      its relationship to the prevailing times in academic medicine.
AB  - PURPOSE: Institutional structure, function, and philosophy reflect the
      organizational needs, and tend to mirror societal values of the times. For many
      years, the field of radiation oncology had among its major academic centers, an
      organization that served as a model for collaboration among health care
      institutions in an effort to serve the common good of its patients, hospitals,
      professional colleagues, and community. For over three decades, the Joint Center
      for Radiation Therapy (JCRT) was a leader in developing new organizational
      approaches for academic and clinical radiation oncology through the philosophy of
      collaboration in patient care, education, and research. METHODS AND RESULTS: In
      tracing the development and changes in organizational philosophy and structure of
      the JCRT, one can see the impact on academic oncology and cancer care through the
      emergence of both radiation and medical oncology as independent subspecialties,
      the importance of the National Cancer Act of 1971 accompanied by the growth of
      the NIH research and training programs and, more recently, the effect of the
      changing attitudes and approaches of hospitals, academicians, practitioners, and
      policy makers to health care delivery, structures, and cooperation. CONCLUSION:
      Lessons learned from the 31-year history of the JCRT may help provide
      organizational insight useful in guiding academic oncology and academic medical
      centers through periods of change.

PMID- 10889392
TI  - Dimethyl sulfoxide protects against thermal and epithermal neutron-induced cell
      death and mutagenesis of Chinese hamster ovary (CHO) cells.
AB  - PURPOSE: To investigate the protective effects of dimethyl sulfoxide (DMSO) on
      cell killing and mutagenicity at the HPRT locus in Chinese hamster ovary (CHO)
      cells against thermal and epithermal neutrons produced at the Kyoto University
      Research (KUR) reactor. METHODS AND MATERIALS: DMSO was added to cells 15 min
      before irradiation and removed 15 min after irradiation. Cells were irradiated by
      thermal and epithermal neutrons with or without boron at 10 ppm. The biological
      endpoint of cell survival was measured by colony formation assay. The
      mutagenicity was measured by the mutant frequency in the HPRT locus. A total of
      378 independent neutron-induced mutant clones were isolated in separate
      experiments. The molecular structure of HPRT mutations was determined by analysis
      by multiplex polymerase chain reaction of all nine exons. RESULTS: The D(0)
      values of epithermal and thermal neutrons in three different modes, i.e.,
      thermal, epithermal, and mixtures of thermal and epithermal, were 0.8-1.2 Gy.
      When cells were treated with DMSO, the D(0) values increased to 1.0-2.3,
      especially in the absence of boron. DMSO showed a protective effect against
      mutagenesis of the HPRT locus induced by epithermal and thermal neutron
      irradiation. After DMSO treatment, the mutagenicity was decreased, especially
      when the cells were irradiated in epithermal neutron mode. Molecular structure
      analysis indicated that total and partial deletions were dominant and the
      incidence of total deletions was increased in the presence of boron in the
      thermal neutron and mixed modes. In the epithermal neutron mode, more than half
      of the mutations were total deletions. When cells were treated with DMSO, the
      incidence of total deletions by thermal neutron irradiation with boron and
      epithermal irradiation decreased. CONCLUSIONS: Our results suggest that DMSO has
      various protective effects against cytotoxic and mutagenic effects of thermal and
      epithermal neutrons, and that the extent of protection is reflected by the
      percentage of absorbed dose distribution for each neutron irradiation mode.

PMID- 10889393
TI  - Biological equivalent dose assessment of the consequences of hypofractionated
      radiotherapy.
AB  - PURPOSE: To investigate the changes in biological effective dose (BED) that occur
      in high-dose regions within a target volume when radiotherapy is
      hypofractionated. METHODS AND MATERIALS: By comparing a standard prescription of
      2 Gy per fraction that is matched to give the same BED as a hypofractionated
      schedule at a standard intersectional prescription point, the BED increments for
      late-tissue effects at a higher dose region within the planning target volume
      (PTV) are compared. The alternative approach of BED matching between a
      conventional and hypofractionated schedule at the high-dose region is also
      considered. The results are presented as a sequence of calculations that can be
      understood by practicing radiation oncologists and in graphical form. RESULTS:
      The BED increment at the high-dose region is marginally increased by
      hypofractionation, although the latter effect is relatively small: up to 5%
      additional BED due to hypofractionation for a 20% increase in physical dose when
      the prescribed fraction size is 6-7 Gy. BED matching for late effects between a
      conventional and hypofractionated schedule at the high-dose region produces lower
      BED values throughout the remaining PTV, but at the expense of a reduced tumor
      control BED. CONCLUSION: Clinical trials that use BED isoeffect matching for late
      reacting tissue effects to design a hypofractioned test schedule should include
      comprehensive calculations of the likely BED in high-dose regions.

PMID- 10889394
TI  - Treatment-plan optimization for soft-tissue sarcoma brachytherapy using a genetic
      algorithm.
AB  - PURPOSE: To describe a treatment-plan optimization system for temporary implant
      of soft-tissue sarcomas using a genetic algorithm, and evaluate its potential
      advantages over manual planning. METHODS AND MATERIALS: A planning system that
      optimizes the distribution of radioactive seeds needed for adequate coverage of
      the target in the treatment of soft-tissue sarcomas has been designed and
      implemented. The treatment-planning procedures include simulation, film
      digitization, target-volume definition, optimized planning, and plan evaluation.
      The input to the optimization program consists of seed coordinates reconstructed
      from isocentric films, prescription points, and a list of available seed
      activities. The optimization is performed using a genetic algorithm. RESULTS:
      Case studies are presented, which compare plans generated by computer
      optimization or by trial and error (manually). As expected, computer-optimized
      plans are often (but not always) superior to manual plans. This is particularly
      evident for situations where (unavoidably) catheters are far apart or irregularly
      spaced, in which case the advantages of optimized planning in terms of tumor
      coverage can be quite dramatic. When the target volume is well contained, the
      optimized plan minimizes the dose to normal tissue. Computer-based optimization
      has the additional advantage of being much faster than manual planning; this is
      valuable because it often reduces the total time the patient will spend in the
      hospital before implantation. CONCLUSION: Optimized planning with a genetic
      algorithm and seeds of different activities significantly improves planning
      efficiency and generally results in improved plan quality. The utility of this
      optimization system is not limited to sarcoma implants.

PMID- 10889395
TI  - A new power law for determination of total (125)I seed activity for ultrasound
      guided prostate implants: clinical evaluations.
AB  - PURPOSE: The intraoperative planning with peripheral loading approach is an
      important technique for ultrasound-guided transperineal prostate implant. In this
      paper a sphero-cylindrical dose model is described to generate a new power law or
      a look-up table for determination of the total (125)I activity required to
      deliver a prescription dose to a given prostate volume. METHODS AND MATERIALS:
      Dose calculations were based on the new standards for (125)I seeds (model 6711)
      implemented by the National Institute of Standards and Technology (NIST) in 1999.
      Using the sphero-cylindrical dose model with peripheral loading approach, a new
      power law for calculating total activity of radioactive iodine required to
      deliver a prescribed dose for the target volume was developed. Accounting for
      random variation of the seed positioning in the prostate and the current air
      kerma strength standard of (125)I seeds, this new power law is formulated as
      follows: A (mCi) = 2.15 d (cm)(2.00) where A is apparent activity in mCi, or A
      (U) = 1. 69 d (cm)(2.00) where A is air-kerma strength in U, required to deliver
      a cumulative dose of 145 Gy to a prostate gland with an average dimension, d, in
      centimeters. RESULTS: The efficacy of using the new power law in prostate
      implants was demonstrated. For clinical evaluations of this new power law, 40
      patients were chosen in 1998. The average D(90) of these 40 patients was 172.0 Gy
      (SD +/- 29 Gy). This means that on the average, 90% of the target volume received
      was 172.0 Gy. The average coverage index (CI) in this study was 94.7 (SD +/-
      4.7). As a result, 94.7% of the target volume received the prescription dose. The
      dose homogeneity index (HI) which measured the degree of the dose inhomogeneity
      was 0.38 (SD +/- 0.21). CONCLUSION: This new and simple power law or a new mCi
      volume look-up table for (125)I seed prostate implantation has been developed and
      formulated for clinical use. Clinical evaluations expressed in quantitative
      parameters such as D(90), CI, and HI in prostate implants have been thoroughly
      analyzed and clearly demonstrated the efficacy of this approach.

PMID- 10889396
TI  - Dosimetric effects of edema in permanent prostate seed implants: a rigorous
      solution.
AB  - PURPOSE: To derive a rigorous analytic solution to the dosimetric effects of
      prostate edema so that its impact on the conventional pre-implant and post
      implant dosimetry can be studied for any given radioactive isotope and edema
      characteristics. METHODS AND MATERIALS: The edema characteristics observed by
      Waterman et al (Int. J. Rad. Onc. Biol. Phys, 41:1069-1077; 1998) was used to
      model the time evolution of the prostate and the seed locations. The total dose
      to any part of prostate tissue from a seed implant was calculated analytically by
      parameterizing the dose fall-off from a radioactive seed as a single inverse
      power function of distance, with proper account of the edema-induced time
      evolution. The dosimetric impact of prostate edema was determined by comparing
      the dose calculated with full consideration of prostate edema to that calculated
      with the conventional dosimetry approach where the seed locations and the target
      volume are assumed to be stationary. RESULTS: A rigorous analytic solution on the
      relative dosimetric effects of prostate edema was obtained. This solution proved
      explicitly that the relative dosimetric effects of edema, as found in the
      previous numerical studies by Yue et. al. (Int. J. Radiat. Oncol. Biol. Phys. 43,
      447-454, 1999), are independent of the size and the shape of the implant target
      volume and are independent of the number and the locations of the seeds
      implanted. It also showed that the magnitude of relative dosimetric effects is
      independent of the location of dose evaluation point within the edematous target
      volume. It implies that the relative dosimetric effects of prostate edema are
      universal with respect to a given isotope and edema characteristic. A set of
      master tables for the relative dosimetric effects of edema were obtained for a
      wide range of edema characteristics for both (125)I and (103)Pd prostate seed
      implants. CONCLUSIONS: A rigorous analytic solution of the relative dosimetric
      effects of prostate edema has been derived for a class of edema characterized by
      Waterman et al. The solution proved that the dosimetric effects caused by the
      edema are universal functions of edema characteristics for a given isotope. It
      provides an efficient tool to examine the relative dosimetric effects of edema
      for any given edema characteristics and for any isotopes that may be considered
      for prostate implants.

PMID- 10889397
TI  - An improved technique for breast cancer irradiation including the locoregional
      lymph nodes.
AB  - PURPOSE: To find an irradiation technique for locoregional irradiation of breast
      cancer patients which, compared with a standard technique, improves the dose
      distribution to the internal mammary-medial supraclavicular (IM-MS) lymph nodes.
      The improved technique is intended to minimize the lung dose and reduce the dose
      to the heart. METHODS AND MATERIALS: The standard technique consists of an
      anterior mixed electron/photon IM-MS field. In the improved technique, an oblique
      electron and an oblique asymmetric photon field are combined to irradiate the IM
      lymph nodes. To irradiate the MS lymph nodes, a combination of an anterior
      electron and an anterior asymmetric photon field is used. For both the standard
      and the improved technique, tangential photon fields are used to irradiate the
      breast. Three-dimensional (3D) treatment planning was performed for 8 patients
      with various breast sizes for these two techniques. Dose-volume histograms (DVHs)
      and normal tissue complication probabilities (NTCPs) were compared for both
      techniques. The field dimensions and energy of the standard technique were
      determined at simulation, whereas for the improved technique the fields were
      designed by CT-based treatment planning. RESULTS: The dose in the breast planning
      target volume was essentially the same for both techniques. For the improved
      technique, combined with 3D localization information, an improvement in the IM-MS
      planning target coverage is seen. The volume within the 95% isodose surface was
      on average 25% (range, 0-64%) and 74% (range, 43-90%) for the standard and
      improved technique, respectively. The heart generally receives less dose with the
      improved technique. However, sometimes a small but acceptable increase in lung
      dose is found. CONCLUSION: The improved technique, combined with localization
      information of the IM-MS lymph nodes, greatly improves the dose distribution in
      the planning target volume for a large group of patients without significantly
      increasing the dose to organs at risk.

PMID- 10889398
TI  - Analysis of dose distribution in gamma knife radiosurgery for multiple targets.
AB  - PURPOSE: The aim of this study is to evaluate the actual effect of irradiation
      for other targets in dose planning for the treatment of multiple metastases with
      Gamma Knife. METHODS AND MATERIALS: We analyzed dose distributions for 51 targets
      in 10 patients with metastatic brain tumors who underwent radiosurgery with Gamma
      Knife for the treatment of more than one target in one session. We made dose
      plans with every attempt to include as many targets as possible and calculate
      dose distributions separately for each dose matrix. We also calculated the
      composite dose distribution by including the effect of all shots used. We
      compared these noncomposite and composite dose distributions. RESULTS: The
      differences in the mean target dose between the noncomposite dose distribution
      and the composite one ranged from 0.0 to 4.5 Gy with a mean of 1.5 Gy and was
      more than 2 Gy in 12 (24%) targets. The difference tended to be larger when
      targets were small in volume and/or the number of targets was large. CONCLUSIONS:
      The effect of irradiation from the shots for other targets was not negligible in
      some cases. This difference of dose distribution should be considered in the
      analysis of clinical outcomes of cases with multiple targets treated in one
      session.

PMID- 10889399
TI  - Detection of fiducial gold markers for automatic on-line megavoltage position
      verification using a marker extraction kernel (MEK).
AB  - PURPOSE: In this study automatic detection of implanted gold markers in
      megavoltage portal images for on-line position verification was investigated.
      METHODS AND MATERIALS: A detection method for fiducial gold markers, consisting
      of a marker extraction kernel (MEK), was developed. The detection success rate
      was determined for different markers using this MEK. The localization accuracy
      was investigated by measuring distances between markers, which were fixed on a
      perspex template. In order to generate images comparable to images of patients
      with implanted markers, this template was placed on the skin of patients before
      the start of the treatment. Portal images were taken of lateral prostate fields
      at 18 MV within 1-2 monitor units (MU). RESULTS: The detection success rates for
      markers of 5 mm length and 1.2 and 1.4 mm diameter were 0.95 and 0.99
      respectively when placed at the beam entry and 0.39 and 0.86 when placed at the
      beam exit. The localization accuracy appears to be better than 0.6 mm for all
      markers. CONCLUSION: Automatic marker detection with an acceptable accuracy at
      the start of a radiotherapy fraction is feasible. Further minimization of marker
      diameters may be achieved with the help of an a-Si flat panel imager and may
      increase the clinical acceptance of this technique.

PMID- 10889400
TI  - Cost-minimization analysis: radiation treatment with and without a multi-leaf
      collimator.
AB  - PURPOSE: To compare the costs of radiation treatment on a linear accelerator with
      a multileaf collimator (MLC) versus treatment on a linear accelerator without an
      MLC. The study was designed to determine whether the increased throughput of
      fields and decreased block cutting made the MLC cost effective from an
      institutional perspective. METHODS AND MATERIALS: The number of fields, basic
      treatment equivalent, equivalent simple treatment visits, and blocks were
      prospectively collected for the four linear accelerators. Building, equipment,
      staffing, and service costs were all obtained in 1999 Australian dollars from the
      manufacturers and hospital department heads. The Joint Radiation Oncology Centre
      at Westmead and Nepean Hospitals, which are Australian public hospitals, runs as
      one unit, with the same staff, and currently operates five linear accelerators.
      Currently, four of the linear accelerators are used for general radiotherapy,
      operating for exactly the same hours; the final machine operates more limited
      hours and is used for specialized radiotherapy techniques and emergency cases.
      RESULTS: The two machines with MLCs, on average, treated 5,169 fields each, while
      the two machines without MLCs treated 4,543 fields in a 3-month period, a 12%
      increase in throughput. The two non-MLC machines required 155 premounted trays
      (PMTs) in total, while the MLC machines required 17 PMTs. Linear accelerators
      with MLCs were demonstrably more efficient, and while their capital costs were
      higher, the reduction in labor costs associated with block cutting and,
      particularly the increased throughput, more than offset these initial costs. The
      total cost of a radiation field with an MLC was found to be $A101.69 compared to
      $A106.98 without an MLC. A multiway sensitivity analysis showed the results to be
      robust. The worst-case scenario was a departmental savings of $A168,000 per year;
      the best-case scenario was a savings of $A680,000 per year. CONCLUSION: Under the
      conditions pertaining to the radiation oncology department in this group of
      hospitals, and in similar departments, the use of an MLC can be justified.

PMID- 10889401
TI  - The exchange of radiotherapy data as part of an electronic patient-referral
      system.
AB  - PURPOSE: To describe the implementation and use of an electronic patient-referral
      system as an aid to the efficient referral of patients to a remote and
      specialized treatment center. METHODS AND MATERIALS: A system for the exchange of
      radiotherapy data between different commercial planning systems and a specially
      developed planning system for proton therapy has been developed through the use
      of the PAPYRUS diagnostic image standard as an intermediate format. To ensure the
      cooperation of the different TPS manufacturers, the number of data sets defined
      for transfer has been restricted to the three core data sets of CT, VOIs, and
      three-dimensional dose distributions. As a complement to the exchange of data,
      network-wide application-sharing (video-conferencing) technologies have been
      adopted to provide methods for the interactive discussion and assessment of
      treatments plans with one or more partner clinics. RESULTS: Through the use of
      evaluation plans based on the exchanged data, referring clinics can accurately
      assess the advantages offered by proton therapy on a patient-by-patient basis,
      while the practicality or otherwise of the proposed treatments can simultaneously
      be assessed by the proton therapy center. Such a system, along with the
      interactive capabilities provided by video-conferencing methods, has been found
      to be an efficient solution to the problem of patient assessment and selection at
      a specialized treatment center, and is a necessary first step toward the full
      electronic integration of such centers with their remotely situated referral
      centers.

PMID- 10889402
TI  - Chlamydia and Chlamydiales: more than meets the eye.
AB  - This review summarizes the dramatic changes that have occurred in the taxonomy of
      bacteria known as Chlamydia. Best known for the diseases they cause in humans,
      these intracellular bacteria also comprise many species that are responsible for
      a wide variety of clinically and economically important diseases in livestock and
      companion animals. The old taxonomy grouped most of these species into C.
      psittaci because systematic methods for routinely distinguishing them were not
      available. DNA-based testing methods are now available that distinguish different
      chlamydial families, genera, and species. This summary reviews these tests and a
      number of oligonucleotide primers that distinguish these groups using PCR and PCR
      RFLP. DNA-based methods are also being used to discover new families of chlamydia
      like bacteria, at least one of which is responsible for abortion in cattle
      (Waddlia chondrophila). This review summarizes the pathogenic roles of the
      Chlamydiaceae, new families, and individual species within the order
      Chlamydiales. These discoveries create opportunities for veterinarians to carry
      out epidemiological studies of chlamydiae that previously were not possible.

PMID- 10889403
TI  - Molecular characterization of canine parvovirus in Brazil by polymerase chain
      reaction assay.
AB  - Canine parvovirus (CPV) was first isolated in 1978 in the USA. Analysis of CPV
      isolates by monoclonal antibodies and restriction enzymes have shown that after
      the first emergence of CPV (CPV-2) it evolved to give rise to new antigenic
      types, which were designated CPV type 2a and type 2b. These new types have
      replaced the original CPV type 2, although the proportions of each of the new
      antigenic types vary in different countries. In Brazil, CPV-like infections were
      first observed in 1979, however, there has been no information concerning the
      antigenic types of CPV prevailing in South America. In this study, we designed a
      PCR assay to type canine parvovirus strains in fecal samples collected from
      symptomatic dogs during 1980 through 1986 and 1990 through 1995. Our data showed
      that the CPV epizootic in Brazil followed the same pattern observed in the USA of
      emergence of CPV-2 followed by replacement by the variants CPV-2a and 2b. The
      predominant strain found during 1980 was CPV-2a, which was substantially replaced
      by CPV-2b from 1990 to 1995.

PMID- 10889404
TI  - Social isolation may influence responsiveness to infection with bovine
      herpesvirus 1 in veal calves.
AB  - An experiment was performed to develop a model to study the impact of stress on
      responsiveness to infection with bovine herpesvirus 1 (BHV1) in veal calves.
      Social isolation after previous group-housing was used as a putatively stressful
      treatment. Group-housed specific pathogen-free veal calves (n=8) were
      experimentally infected with BHV1 at the age of 12 weeks. Half of the calves were
      socially isolated at the time of infection. Clinical, virological and serological
      responses to BHV1, and adreno-cortical reactivity to exogenous ACTH were
      examined. In comparison with group-housed calves, calves socially isolated at the
      time of infection showed a diminished clinical and fever response, and delayed
      viral excretion after primary infection with BHV1. Four weeks after social
      isolation, basal cortisol levels before, and the integrated cortisol response
      after administration of a low dose of ACTH, were significantly depressed in
      socially isolated calves. The results suggest that social isolation in veal
      calves influences the response to an experimental BHV1 infection. A possible
      mechanism is discussed.

PMID- 10889405
TI  - A rapid and sensitive PCR-based diagnostic assay to detect bovine herpesvirus 1
      in routine diagnostic submissions.
AB  - We describe a rapid, sensitive and specific polymerase chain reaction (PCR) assay
      for the detection of BHV1 DNA in a range of routine diagnostic submissions
      without the need for prior virus isolation. The assay, which is based on the
      selected amplification of a portion of the viral tk gene, detected both BHV1.1
      and BHV1.2 subtypes in a panel of 15 characterised field isolates, and its
      sensitivity was estimated to be <0.125 TCID(50). BHV2, alcephaline herpesvirus,
      BHV4, equine herpesvirus 1 (EHV1), EHV4 and pseudorabies virus were not detected
      confirming the specificity of the assay. One hundred and five diagnostic
      submissions, including tissues, nasal secretions and nasal swabs were taken from
      cattle with respiratory disease and tested using the routine methods of virus
      isolation (VI) and the fluorescent antibody test (FAT), and the results were
      compared with those obtained by PCR. The PCR assay detected BHV1 DNA in all
      samples that were positive by VI. BHV1 DNA was also detectable by PCR in raw and
      extended semen samples at a sensitivity of 1 TCID(50) per 50microl. The assay
      also detected BHV5, permitting differentiation between it and BHV1 by virtue of
      the size of the amplified PCR product. The PCR assay is more sensitive and
      independent of sample quality than either virus isolation or FAT, and it is
      faster than virus isolation. The sample preparation method is simple with few
      steps involved. There are no extra post-amplification blotting/hybridisation
      steps and the assay is not based on a nested PCR strategy that might otherwise
      exacerbate the problem of oversensitivity/contamination in the routine use of
      such a test in a diagnostic laboratory. This assay would permit discrimination
      between those animals naturally infected with wild type BHV1 and those vaccinated
      with tk-BHV1 strains.

PMID- 10889406
TI  - Genotypic characterisation by PFGE of Salmonella enterica serotype Enteritidis
      phage types 1, 4, 6, and 8 isolated from animal and human sources in three
      European countries.
AB  - A total of 101 strains of Salmonella Enteritidis phage types (PT) 1, 4, 6, and 8
      from Denmark, England and Spain were studied by PFGE to elucidate genetic
      relationships among strains isolated from animal, human and environmental sources
      between 1983 and 1997. Analysis with Xba I, Bln I and Spe I enzymes showed that
      the power of discrimination of this method was increased by the combination of
      the three enzymes (D=0.802), subdividing the strains into 28 genomic groups or
      genotypes. Many of the PT1, PT4, and PT6 strains from the three countries shared
      the same PFGE combination profile A1-A1-A1, confirming the close relationship
      among these phage types and the protracted spread of a single clone over a large
      geographical area. In general, strains from Denmark showed more variation in
      their PFGE profiles than those from England and Spain. PT4 strains exhibited
      genetic homogeneity in the three countries independently of their sources and
      period of isolation. Spe I gave the highest index of discrimination among PT6
      strains as evidenced by a variety of PFGE profiles. The data clearly confirmed
      that PT8 strains isolated in the three countries were of a unique clonal origin,
      and the PFGE combination profile A10-A10-A1 was predominant and specific for this
      phage type. It is concluded that PFGE, in combination with phage typing,
      represents a suitable tool for the epidemiological typing of Salmonella
      Enteritidis strains which could be used for investigations or surveillance of the
      international spread of these clones.

PMID- 10889407
TI  - A comparison of four serological tests for the diagnosis of caseous lymphadenitis
      in sheep and goats.
AB  - A double antibody sandwich ELISA (ELISA A) developed for the detection of
      Corynebacterium pseudotuberculosis infection in sheep and goats was modified to
      improve its sensitivity. To establish the sensitivity and specificity of this
      modified ELISA (ELISA B), sera from 183 sheep and 186 goats were tested using
      ELISAs A and B. Comparison was also made with two further ELISAs (C and D)
      developed in Australia that, respectively, detect antibodies to cell wall
      antigens or toxin.ELISA B had the best performance of the four tests. Its
      specificity was 98+/-1% for goats and 99+/-1% sheep. Its sensitivity was 94+/-3%
      for goats and 79+/-5% for sheep. ELISA B will now be tested for use in caseous
      lymphadenitis eradication and control programmes in The Netherlands. It will also
      be used in experimental studies of CL in Scotland.

PMID- 10889408
TI  - IgG isotype antibody responses to epitopes of the Mycobacterium bovis protein
      MPB70 in immunised and in tuberculin skin test-reactor cattle.
AB  - Serological assays may have merit in identifying animals in advanced stages of
      bovine tuberculosis, but most tests have had sub-optimal sensitivities and
      specificities. The Mycobacterium bovis protein MPB70 has been identified as a B
      cell target with diagnostic potential in measurement of pre- and post-skin-test
      antibody responses. One observation, which has potential practical application,
      has been that skin testing with tuberculin boosts IgG(1) anti-MPB70 antibody
      responses in cattle with tuberculous lesions. However, serological cross
      reactivities with bacteria, such as Nocardia asteroides, have been described for
      this protein. With the aim of identifying candidate reagents for improved
      diagnostic tests, this study investigated IgG isotype antibody responses to MPB70
      at the epitope level and, because of the previous findings, focused on IgG(1)
      responses following skin testing. Screening of a panel of overlapping synthetic
      peptides using sera from cattle immunised with MPB70 and cattle infected with M.
      bovis showed that two regions of the protein (residues 21-70 and 101-120) contain
      dominant B-cell epitopes. No individual epitope appeared to be selectively
      recognised by one isotype of IgG antibody. Investigation of IgG(1) responses
      showed that recognition of the epitope within residues 51-70 was boosted strongly
      by tuberculin injections in skin-test positive cattle and that this memory
      response was generally a feature of cattle which were found to have macroscopic,
      tuberculous lesions.

PMID- 10889409
TI  - Identification of porcine intestinal spirochetes by PCR-restriction fragment
      length polymorphism analysis of ribosomal DNA encoding 23S rRNA.
AB  - The Brachyspira (formerly Serpulina) species rrl gene encoding 23S ribosomal RNA
      (rRNA) was used as a target for amplification of a 517bp DNA fragment by
      polymerase chain reaction (PCR). The primers for PCR amplification had sequences
      that were conserved among Brachyspira 23S rRNA gene and were designed from
      nucleotide sequences of Brachyspira hyodysenteriae, Serpulina intermedia,
      Brachyspira innocens and Brachyspira pilosicoli available from the GenBank
      database. Digestion of PCR-generated products from reference and field isolates
      of swine intestinal spirochetes with restriction enzymes Taq I and Alu I revealed
      five restriction fragment length polymorphism (RFLP) patterns. Each RFLP pattern
      corresponded to previously established genetic groups including B. hyodysenteriae
      (I), S. intermedia/B. innocens (II), Brachyspira murdochii (III), B. pilosicoli
      (IV) and B. alvinipulli (V). The 23S rRNA PCR/RFLP provided a relatively simple
      genotypic method for identification of porcine pathogenic B. hyodysenteriae and
      B. pilosicoli.

PMID- 10889410
TI  - Cloning and kinetics of expression of Brucella abortus heat shock proteins by
      baculovirus recombinants.
AB  - In an effort to develop genetically engineered Brucella abortus (BA) vaccines,
      the genes encoding heat shock proteins (HSPs) GroEL, GroES, and HtrA were cloned
      and expressed in the BAC-TO-BAC Baculovirus System, and the kinetics of protein
      expression were analyzed using various insect cell lines in suspension cultures,
      different cell densities in suspension cultures, multiplicities of infection and
      recombinant virus replication times. Trichoplusia ni cells expressed only BA
      HtrA, but Spodoptera frugiperda (Sf9) cells expressed all three recombinant
      proteins. The best GroEL expression was achieved by infecting 2x10(6) Sf9
      cells/ml with an MOI 10 of recombinant virus and harvesting the cells after 96h
      of virus replication. GroES and HtrA were best expressed when infecting 2x10(6)
      Sf9 cells/ml with an MOI 1 of recombinant viruses and harvesting the cells after
      120h of virus replications. Under these conditions BA recombinant HSPs were
      expressed as follows: GroEL at 16% of the total cellular proteins (105microg/ml
      concentration); GroES 2% (15.25microg/ml); and HtrA 8% (84.48microg/ml). This is
      the first report of cloning and expression of BA genes in the baculovirus system.

PMID- 10889411
TI  - Opposite clear corneal incisions.

PMID- 10889413
TI  - Refractive surgical problem

PMID- 10889412
TI  - Consultation section: refractive surgical problem.

PMID- 10889414
TI  - Refractive surgical problem: reply

PMID- 10889416
TI  - Refractive surgical problem: reply

PMID- 10889415
TI  - Refractive surgical problem: reply

PMID- 10889418
TI  - Refractive surgical problem: reply

PMID- 10889417
TI  - Refractive surgical problem: reply

PMID- 10889419
TI  - Refractive surgical problem: reply

PMID- 10889420
TI  - Refractive surgical problem: reply

PMID- 10889421
TI  - Refractive surgical problem: reply

PMID- 10889422
TI  - Opposite clear corneal incisions to correct pre-existing astigmatism in cataract
      surgery.
AB  - In cataract surgery, the clear corneal incision (CCI) has a small flattening
      effect on corneal curvature, which can be used to reduce pre-existing astigmatism
      (PEA). Adding an identical, penetrating CCI opposite the first one can enhance
      the flattening effect. The paired opposite CCIs (OCCIs) are placed on the
      steepest meridian axis to flatten it. One CCI is used to perform cataract
      surgery, and the opposite CCI is made to enhance the flattening effect on the
      cornea to modulate PEA. During the past 12 months, we have used 2.8 to 3.5 mm
      OCCIs in 33 eyes with PEA greater than 2.00 diopters (D) having cataract surgery.
      The mean astigmatism correction achieved with this technique was 2.06 D. This
      technique is simple and effective and yields stable results that rival those of
      arcuate keratotomy. The OCCI technique has a potential application for the
      correction of astigmatism in general refractive surgery. Opposite clear corneal
      incision nomograms with variables such as width, length, and distance from the
      limbus will be needed for future applications.

PMID- 10889423
TI  - Contrast sensitivity assessment using the visual performance tester.
AB  - The visual performance tester (VPT), a device that uses patient response time as
      a variable to assess visual power, is described. Results in 126 emmetropic eyes
      that had not had surgery are presented. The VPT provides more complete and
      accurate information about visual performance than the standard visual acuity
      examination because the device considers all variables involved in visual
      function results.

PMID- 10889424
TI  - Dysphotopsia in phakic and pseudophakic patients: incidence and relation to
      intraocular lens type(2).
AB  - PURPOSE: To determine the relationship between various intraocular lens (IOL)
      types and the incidence of unwanted light images. SETTING: The Moran Eye Center,
      University of Utah, Salt Lake City, Utah, USA. METHODS: A telephone questionnaire
      was administered to 302 postoperative patients who had received 1 of 6 commonly
      used IOLs between January and September 1998. Patients were included only if they
      had uneventful cataract surgery, no additional ocular pathology, and a
      postoperative best corrected visual acuity of 20/25 or better. A control group of
      50 patients with the diagnosis of presbyopia only also participated in the
      questionnaire. Patients reported on incidence of glare, light sensitivity, and
      unwanted images. The data were analyzed for statistically significant
      relationships between incidence of photopsias and IOL type. RESULTS: The AcrySof
      5.5 mm, AcrySof 6.0 mm, and SI-40 groups reported significantly more unwanted
      images than the control group (P =.0014). The 2 AcrySof groups also reported a
      greater incidence of light to the side causing a central flash, and the SI-40
      group, a higher incidence of glare. The control group was more likely to
      experience symptoms of glare than any pseudophakic group. Overall, a mean of 49%
      of patients reported some light-related phenomenon postoperatively. The majority
      in all groups reported being satisfied with their eyesight despite the light
      related problems. CONCLUSIONS: A significant number of pseudophakic patients
      reported symptoms of dysphotopsia. Patients who received an acrylic IOL with
      flattened edges were at increased risk of experiencing images associated with
      edge reflections. The SI-40 lens group, although less than the AcrySof groups,
      reported a higher incidence of glare than the non-AcrySof groups; however, it
      also had the highest number of patients still driving at night. The phakic
      population commonly experienced glare reported as more severe than several of the
      IOL groups.

PMID- 10889425
TI  - Evaluation of giant-cell deposits on foldable intraocular lenses after combined
      cataract and glaucoma surgery.
AB  - PURPOSE: To compare the incidence of inflammatory giant-cell deposits (IGCDs) on
      various foldable intraocular lenses (IOLs) after combined cataract and glaucoma
      surgery. SETTING: The Phillips Eye Institute, Minneapolis, Minnesota, USA.
      METHODS: In this prospective randomized clinical trial, 128 patients were
      randomized to receive a single-piece, first-generation silicone lens (n = 36); a
      3-piece acrylic lens (n = 40); or 3-piece, second-generation silicone lens (n =
      52). All patients had combined phacoemulsification and trabeculectomy with
      mitomycin-C by 1 surgeon using a standardized technique. Dilated biomicroscopy
      was used to identify and quantitate IGCDs on the surface of the IOLs using a 6
      point grading scale. RESULTS: Inflammatory giant-cell deposits were identified on
      21 of 128 IOLs. Lens design was the most significant risk factor for deposit
      formation (P =.004). Inflammatory giant-cell deposits were most common in the
      first-generation silicone plate lens group (33%), less common in the acrylic lens
      group (15%), and least common in the 3-piece, second-generation silicone group
      (5.8%). Density of the deposits was significantly greater on the plate lens than
      the acrylic or the 3-piece silicone lenses (P <.0001). Although IOL design was
      the most significant risk factor for IGCD formation, other significant risk
      factors included intraoperative pupil stretch (P =.02) and preoperative miotic
      use (P =.04). CONCLUSION: Inflammatory giant-cell deposit formation was
      significantly greater on first-generation silicone plate IOLs than on acrylic or
      second-generation silicone IOLs. The deposits were somewhat more common on
      acrylic IOLs than on second-generation silicone IOLs. However, this difference
      was not clinically or statistically significant.

PMID- 10889426
TI  - Role of optic capture in congenital cataract and intraocular lens surgery in
      children.
AB  - PURPOSE: To evaluate the role of optic capture in eyes having cataract
      extraction, anterior vitrectomy, and intraocular lens (IOL) implantation for
      congenital cataract. SETTING: Iladevi Cataract & IOL Research Centre, Ahmedabad,
      India. METHODS: This prospective study comprised 40 eyes of 28 children, whose
      mean age was 26.08 months (range 4 to 55 months). Primary posterior continuous
      curvilinear capsulorhexis, anterior vitrectomy, and IOL implantation were
      performed in all eyes. Eyes were randomly assigned to 1 of 2 groups of 20 each:
      in 1 group, optic capture would be used and in the other, the noncapture
      technique. Permanent optic capture was achieved in 14 eyes, and 26 eyes had no
      optic capture. Mean follow-up was 16.53 months (range 5 to 24 months). A Student
      t test and chi-square test were used for statistical analyses. RESULTS: All eyes
      in both groups maintained a clear visual axis. One eye in the optic-capture group
      developed a membrane in front of the IOL that required a secondary procedure.
      Posterior synechia formation was significantly greater in the optic-capture group
      (P =.04), as were deposits on the IOL optic (P =.0086). Although all eyes in both
      groups maintained a clinically centered IOL, geometric decentration was more
      common in the no-capture group (P =.0000). CONCLUSION: Optic capture resulted in
      better IOL centration but predisposed the eye to an increased uveal inflammatory
      response.

PMID- 10889427
TI  - Vitrectomy and lensectomy in the management of posterior dislocation of lens
      fragments.
AB  - PURPOSE: To study the visual results and complications in patients treated by
      vitrectomy and lensectomy for posterior dislocation of lens fragments during
      phacoemulsification. SETTING: University Hospital of Wales, Cardiff, United
      Kingdom. METHODS: This retrospective study was carried out between 1995 and 1998.
      Eighteen patients had a vitrectomy and lensectomy for posterior dislocation of
      lens fragments. The referral patterns, the presenting features, and the
      complications were recorded. The patients were invited for a final review to
      assess and record the final visual outcome and for a detailed ocular examination.
      RESULTS: The median age of the patients was 76 years. The youngest patient was 62
      years and the oldest, 87 years. The median time of referral was 1 day (range 0 to
      67 days). The median timing of the surgery was 6 days (range 2 to 77 days);
      however, 5 patients had a vitrectomy-lensectomy performed at the time of cataract
      surgery (day 0). Uveitis was present in 100% of patients, corneal edema in 76.0%,
      and ocular hypertension in 38.4%. Median follow-up was 12 months (range 6 to 34
      months). Visual acuity was 6/12 or better in 83.3% of patients. Two patients were
      treated for retinal tears, 2 had postoperative uveitis, 2 had macular pucker, and
      2 had ocular hypertension. There was no statistically significant association
      between final visual outcome and grade of the surgeon performing the cataract
      operation, the presence of an intraocular lens at the time of cataract surgery,
      the timing of the vitrectomy-lensectomy, or the presence of previtrectomy uveitis
      or high intraocular pressure (IOP). CONCLUSIONS: Early recognition of dislocated
      lens fragments and prompt assessment for vitrectomy-lensectomy produced excellent
      visual results and few complications. The corneal edema, uveitis, and high IOP
      resolved with the vitrectomy-lensectomy.

PMID- 10889428
TI  - Hardness and ultrasonic characteristics of the human crystalline lens.
AB  - PURPOSE: To evaluate the relationship between hardness of the human crystalline
      lens and its acoustic characteristics. SETTING: St. George's Hospital Medical
      School, University of London, London, United Kingdom. METHODS: Cataractous lenses
      from patients who had extracapsular cataract surgery were studied for hardness
      and ultrasonic characteristics. Lens hardness was assessed with an automated
      guillotine. Ultrasound velocity and attenuation were measured with a scanning
      acoustic macroscope using the pulse transmission reflection method. RESULTS:
      Thirty-seven lenses from 37 patients (mean age 75.5 years) were evaluated. Lens
      hardness was associated with ultrasound attenuation (r = 0.65, P <.0001) and
      attenuation frequency gradient (r = 0.67, P <.0001). The correlation of hardness
      with mean ultrasound velocity was not significant (r = 0.22, P =.2). CONCLUSIONS:
      The attenuation of ultrasound waves by the human crystalline lens correlated with
      its hardness. Ultrasonography can be used to evaluate lens hardness.

PMID- 10889429
TI  - Subjective visual experience during phacoemulsification and intraocular lens
      implantation using retrobulbar anesthesia.
AB  - PURPOSE: To investigate the subjective visual experience of patients during
      phacoemulsification and intraocular lens (IOL) implantation using retrobulbar
      anesthesia. SETTING: Department of Ophthalmology, Tan Tock Seng Hospital,
      Singapore. METHODS: Seventy cataract patients who had routine phacoemulsification
      and posterior chamber IOL implantation under retrobulbar anesthesia were
      interviewed on the day of their surgery regarding their visual experience in the
      operated eye during surgery. Thirty-nine men (55.7%) and 31 women (44.3%) were
      included in the study. Their mean age was 65.1 years (range 37 to 87 years).
      Preoperative best corrected visual acuity ranged from 6/12 to counting fingers.
      Sixty eyes (85.7%) had no ocular pathology other than cataract. Eleven patients
      (15.7%) reported no light perception during the surgery. The rest reported they
      could see light (59 patients, 84.3%), 1 or more colors (39 patients, 55.7%),
      flashes (35 patients, 50.0%), movements (34 patients, 48.6%), instruments (12
      patients, 17.1%), and the surgeon's fingers or hands (11 patients, 15.7%). The
      colors seen included red (23 patients, 32.9%), blue (17 patients, 24.3%), yellow
      (12 patients, 17.1%), green (7 patients, 10. 0%), and orange (1 patient, 1.4%).
      Eight patients (11.4%) saw a spectrum of colors similar to a rainbow. Thirty-one
      patients (44.3%) reported that the brightness of light changed during surgery.
      Five patients (7.1%) found their visual experience frightening. Patients who
      reported seeing colors (P =.048, Fisher exact test) and flashes of light (P
      =.027, Fisher exact test) were more likely to find the experience frightening.
      There was no statistically significant correlation between those who found the
      experience frightening and patient sex or age, length of surgery, or history of
      cataract surgery in the fellow eye. CONCLUSIONS: Many patients having
      phacoemulsification and IOL implantation under retrobulbar anesthesia experienced
      a variety of visual sensations that were frightening in a small proportion of
      cases.

PMID- 10889430
TI  - Contrast sensitivity measured by 2 methods after photorefractive keratectomy.
AB  - PURPOSE: To study contrast sensitivity in eyes that had flying-spot excimer laser
      photorefractive keratectomy (PRK) and to compare a subjective method (Vision
      Contrast Test System [VCTS] 6500) and an objective method (visual evoked
      potential [VEP]) of measuring contrast sensitivity. SETTING: Istituto Clinica
      Oculistica, Universita degli Studi, Bari, Italy. METHODS: Contrast sensitivity
      changes over time were evaluated in 26 eyes. The baseline values were compared
      with measurements 3, 6, and 12 months after PRK using the VCTS 6500 and VEP.
      Contrast threshold and VEP amplitude were classified by myopic correction.
      RESULTS: Contrast threshold values changed significantly over time (P <.001).
      Significant differences were found between mean contrast threshold preoperatively
      and 12 months postoperatively (P <.001) at all spatial frequencies. A significant
      relationship was established between baseline and 12 month measurements at 18
      cycles per degree. Mean VEP amplitude measurements also changed significantly
      over time (P <.001) and showed a significant relationship between baseline and 12
      month measurements (P <.001). A significant relationship was also established
      between baseline and 12 month VEP amplitude values at 100% of grating contrast.
      Patients with high myopia complained significantly more at a lower contrast
      threshold and at lower VEP amplitude values than patients with low myopia.
      CONCLUSIONS: Three months after PRK, contrast threshold and VEP amplitude values
      were reduced. Partial recovery was established at 6 months, although patients
      reported permanent impairment under low-contrast conditions, especially if the
      myopia correction was more than 6.0 diopters.

PMID- 10889431
TI  - Natural history of central islands after laser in situ keratomileusis.
AB  - PURPOSE: To assess the incidence and natural history of central islands following
      laser in situ keratomileusis (LASIK) and evaluate the association of central
      island characteristics with visual acuity. SETTING: Department of Ophthalmology,
      China Medical College Hospital, Taichung, Taiwan. METHODS: A consecutive series
      of 406 eyes of 212 patients who had LASIK was retrospectively evaluated.
      Uncorrected visual acuity (UCVA) was measured and corneal topography performed
      preoperatively and 1 week and 1, 3, 6, and 9 months postoperatively. Best
      spectacle-corrected visual acuity (BSCVA) was evaluated preoperatively and 1, 3,
      and 6 months postoperatively. RESULTS: The topographic images obtained at 1 week
      demonstrated central islands in 23 eyes of 20 patients (5.7%). No new cases of
      central island formation were identified after 1 week. Of the 23 eyes with
      central islands, the 6 month post-LASIK maps were available in 20 eyes of 18
      patients. There was a significant difference in the size and power of the central
      islands between 1 week and 6 months. However, the power and size decreased
      slowly. Within 6 months, only 5 of 20 central islands (25.0%) had resolved. Eight
      eyes were undercorrected, and 1 eye lost 2 lines of BSCVA. Central islands larger
      than 1.8 mm or 3.0 diopters (D) were significantly correlated with lower UCVA.
      CONCLUSION: Most central islands that occur with LASIK persist more than 6
      months. Large central islands (>/=1.8 mm or >/=3.0 D) are risk factors for lower
      UCVA. Preventive measures are necessary.

PMID- 10889432
TI  - Scotopic measurement of normal pupils: Colvard versus Video Vision Analyzer
      infrared pupillometer.
AB  - PURPOSE: To prospectively measure the scotopic pupil diameter in a normal
      population and to compare 2 infrared pupillometers for these measurements.
      SETTING: Johann Wolfgang Goethe-University, Department of Ophthalmology,
      Frankfurt am Main, Germany. METHODS: The Colvard infrared pupillometer was
      compared to the Video Vision Analyzer (VIVA) infrared pupillometer under scotopic
      light conditions in 33 participants (aged 19 to 55 years). Reliability was
      assessed by 2 independent examiners (E1, E2). Statistical analysis was performed
      using a comparison method by Bland and Altman. RESULTS: Mean pupil diameter was
      6.16 mm +/- 1.20 (SD) (range 3.20 to 9.00 mm) with all measurements taken under
      scotopic illumination. The mean scotopic pupil diameter was 6.08 +/- 1.16 mm
      (range 3.2 to 8.4 mm) with the Colvard pupillometer and 6.24 +/- 1.28 mm (3.5 to
      9.0 mm) with the VIVA pupillometer. The mean differences between the Colvard and
      VIVA were -0.27 mm (E1) and -0.05 mm (E2). Limits of agreement ranged from 1.4
      (Colvard) to 2.4 (VIVA). The coefficients of repeatability ranged from 0.7
      (Colvard) to 1.1 (VIVA). CONCLUSIONS: A mean scotopic pupil diameter of 6.15 mm
      with a maximal pupil size of 9.00 mm can be expected in a normal population; this
      should be considered in refractive corneal and refractive lens surgery.
      Measurements with the Colvard pupillometer were more reliable and precise than
      those with the VIVA pupillometer.

PMID- 10889433
TI  - Influence of excimer laser photorefractive keratectomy on the posterior corneal
      surface.
AB  - PURPOSE: To investigate the influence of excimer laser photorefractive
      keratectomy on the refraction and geometry of the posterior corneal surface.
      SETTING: Miyata Eye Hospital, Miyazaki, Japan. METHODS: Thirty-seven eyes of 21
      patients with refractive errors of -2.00 to -9.75 diopters (D) were treated with
      the VISX Twenty-Twenty excimer laser system. The refractive and anteroposterior
      changes in the posterior corneal surface were measured using scanning-slit
      corneal topography (Orbscan, Orbtek, Inc.) preoperatively and 1 week and 1 and 3
      months postoperatively. RESULTS: Mean posterior corneal refraction was -6.51 D +/
      0. 29 (SD) preoperatively; it decreased to -7.00 +/- 0.49 D, -7.00 +/- 0.55 D,
      and -6.92 +/- 0.42 D at 1 week, 1 month, and 3 months, respectively (P <.001,
      Tukey multiple comparison). Mean forward shift of the posterior corneal surface
      was 29.5 +/- 1.9 microm, 34.4 +/- 3.4 microm, and 54.3 +/- 4.0 microm at 1 week,
      1 month, and 3 months, respectively. The amount of posterior corneal refractive
      change correlated with the degree of forward shift (r= -0.691, P <. 001). The
      residual corneal thickness correlated with the refractive change (r = 0.524, P
      <.001) and the forward shift (r = -0.851, P <. 001) of the posterior corneal
      surface. CONCLUSION: Photorefractive keratectomy induced significant refractive
      changes in the posterior corneal surface and forward shift of the cornea, both of
      which correlated with the thinness of the residual cornea.

PMID- 10889434
TI  - Changes in posterior corneal curvature after photorefractive keratectomy.
AB  - PURPOSE: To determine whether myopic ablation by excimer laser photorefractive
      keratectomy (PRK) affects only the anterior curvature of the cornea or whether
      changes also occur in the posterior corneal curvature. SETTING: Department of
      Optometry and Neuroscience, UMIST, and Optimax Laser Eye Clinic, Manchester,
      United Kingdom. METHODS: Sixteen patients who presented for correction of myopia
      in 1 eye by excimer laser PRK were followed for 3 months. Only newly presenting
      patients were recruited, and the untreated eyes were used as controls. The
      patients were examined at the initial visit (0 week) and 6 and 12 weeks post-PRK.
      Measurements included Orbscan topography and pachymetry, autokeratometry, and
      ultrasound pachymetry. RESULTS: The mean patient age of the 8 men and 8 women was
      29.6 years +/- 8.6 (SD) (range 20 to 47 years). The attempted mean spherical
      equivalent correction was between -1.73 and -6.43 diopters. Anterior corneal
      curvature and corneal thickness in the treated eyes changed systematically in
      relation to the amount of ablation. Posterior corneal curvature steepened in
      relation to the dioptric power treated. There were systematic differences between
      the pachymetry values obtained with the Orbscan and the ultrasound pachymeter.
      CONCLUSIONS: The results suggest that after myopic PRK, the thinner, ablated
      cornea may bulge forward slightly to steepen both anterior and posterior
      curvatures. This may account for the regression toward myopia that is typically
      found in the first few days posttreatment. The forward bulging is similar to the
      corneal relaxation effects observed after radial keratotomy.

PMID- 10889435
TI  - Surgical results of photorefractive keratectomy with different operative modes.
AB  - PURPOSE: To compare the predictability, efficacy, and safety of photorefractive
      keratectomy (PRK) using different operative modes. SETTING: National Taiwan
      University Hospital, Taipei, Taiwan. METHODS: One hundred fifty-three eyes of 80
      patients who had PRK for myopia with a follow-up of at least 6 months were
      studied. All patients were sequentially assigned to 1 of the following surgical
      modes: mode 1: PRK with the Summit OmniMed excimer laser; mode 2: PRK with the
      Summit Apex Plus laser; mode 3: PRK with the Summit Apex Plus laser with anti
      central-island pretreatment. RESULTS: Six months after treatment, a homogeneous
      topographic pattern was seen in 76% of mode 1 eyes, 70% of mode 2 eyes, and 88%
      of mode 3 eyes. In the low myopia group (< or =-6.0 diopters [D]), the mean
      residual refractive error was -0.79 D +/- 0.59 (SD) in mode 1, -0.94 +/- 1.02 D
      in mode 2, and -0.31 +/- 0.42 D in mode 3. In the high myopia group (>-6.0 D), it
      was -1.93 +/- 1.51 D, -1.54 +/- 0.88 D, and -0.70 +/- 0.81 D, respectively.
      Uncorrected visual acuity of 20/25 or better was achieved in 81% of mode 1 eyes,
      56% of mode 2 eyes, and 89% of mode 3 eyes in the low myopia group, and in 48%,
      28%, and 72%, respectively, in the high myopia group. CONCLUSIONS:
      Photorefractive keratectomy appears to be a predictable and effective procedure.
      The best results were achieved with the Summit Apex Plus laser with anti-central
      island pretreatment, followed by the Summit OmniMed laser. The Summit Apex Plus
      laser without anti-central-island pretreatment produced less satisfactory
      results.

PMID- 10889436
TI  - Adenovirus-mediated gene transfer to human lens epithelial cells in organ
      culture.
AB  - PURPOSE: To assess the feasibility of using recombinant adenovirus vectors to
      transduce the human lens epithelial cells (LECs) involved in posterior capsule
      opacification (PCO). SETTING: Department of Ophthalmology and Molecular Medicine
      Unit, University of Manchester, Manchester, United Kingdom. METHODS: Seventeen
      human lens capsules were maintained in organ culture to allow LECs to proliferate
      onto the posterior capsule. Partly covered and completely covered capsules were
      infected with a recombinant adenovirus vector RAd35, encoding for the marker gene
      beta-galactosidase at plaque-forming units per milliliter (pfu/mL) ranging from
      10(7) to 10(10) for up to 48 hours. Assessment of infection and transduction of
      the marker gene were achieved by calculating the percentage of cells exhibiting X
      gal staining both macroscopically and microscopically. RESULTS: Staining appeared
      to be dependent on virus dose, with most intense staining at doses of 10(8) and
      10(9) pfu/mL with decreased staining at higher and lower viral doses. Microscopic
      assessment demonstrated that all cells expressed beta-galactosidase when infected
      with 10(9) pfu, 84% at 10(8) pfu, and 45% at 10(7) pfu. At 10(10) pfu, some
      cytotoxicity was observed. CONCLUSIONS: These results indicate that recombinant
      adenoviruses can be used to transfer genes to the LECs involved in PCO. The
      transfer of cytotoxic genes after cataract surgery may be considered a preventive
      measure for PCO.

PMID- 10889437
TI  - Effect of topical anti-inflammatory drugs on corneal and limbal wound healing.
AB  - PURPOSE: To examine the effect of topical treatment with either steroidal or
      nonsteroidal anti-inflammatory drugs (NSAIDs) on the wound healing of corneal and
      limbal incisions using histologic criteria. SETTING: Loyola University Medical
      Center, Maywood, Illinois, USA. METHODS: Eighteen eyes of 9 cats were used for
      the study. All right eyes received a temporal limbal incision and the left eyes,
      a clear corneal incision. All eyes were treated with ofloxacin 0.3%
      postoperatively for 3 days. The animals were equally divided among 3 groups.
      Group 1 received topical steroid drops (prednisolone acetate 1%) for 7 days
      maximum; Group 2 received topical NSAID drops (ketorolac tromethamine 0.5%) for 7
      days maximum; Group 3 received no additional treatment. One animal from each
      group was killed and the eye enucleated 3, 7, or 28 days postoperatively. The
      eyes were processed for staining with hematoxylin-eosin and smooth muscle actin,
      and corneal sections were evaluated in a blind fashion by an ophthalmic
      pathologist. RESULTS: Three and 7 days after surgery (1) the limbal incision
      exhibited more prominent wound healing than the similarly treated clear corneal
      incision, and (2) the steroid-treated corneas had less wound healing than
      untreated or NSAID-treated corneas. At 28 days, the wounds in all eyes were
      almost completely healed. CONCLUSIONS: Limbal incisions heal faster than clear
      corneal incisions. Steroids, but not NSAIDs, inhibit wound healing. Cataract
      surgery using limbal incisions and postoperative topical NSAIDs may result in
      faster wound healing and provide a reduced risk of related postoperative
      complications.

PMID- 10889438
TI  - The capsular tension ring: designs, applications, and techniques.
AB  - Originally, the open poly(methyl methacrylate) (PMMA) capsular tension ring (CTR)
      was designed to compensate for zonular defects or to stretch the posterior
      capsule in highly myopic eyes not receiving an intraocular lens (IOL). We address
      the variety of subsequent designs, applications, and techniques that have
      evolved. With pre-existing or intraoperative zonular defects, a standard CTR may
      be inserted before or at any time during cataract removal to maintain or re
      establish an extended capsular diaphragm. For profound zonular dialysis or
      weakness, a CTR was designed for scleral fixation. Capsular tension rings with
      integrated tinted sector shields have been developed to compensate for sector
      iris colobomas or aniridia. The CTR has also been used as a measuring gauge for
      in vivo quantification of capsule dimensions and postoperative capsular
      shrinkage. The CTR has improved control during primary posterior capsulorhexis
      and prevented oval distortion along the lens axis postoperatively. During
      combined cataract and vitreous surgery, a CTR prevents capsule damage and
      provides undisturbed peripheral visualization before IOL implantation. Capsular
      tension rings may also influence capsule opacification formation. A special band
      shaped CTR with sharp edges was developed to inhibit lens epithelial cell
      migration and avoid capsulorhexis-optic contact.

PMID- 10889439
TI  - Practice styles and preferences of ASCRS members--1999 survey.
AB  - A survey of the practice styles and preferences of members of the American
      Society of Cataract and Refractive Surgery with United States ZIP codes was
      performed in September 1999. Approximately 27% (1342) of 4932 questionnaires
      mailed were returned before the November cutoff. Three profile questions were
      used to cross-tabulate: age of the opthalmologist, geographic location, and
      volume of cataract surgery per month. Current data were compared with data of
      previous surveys.

PMID- 10889440
TI  - Macular hemorrhage after laser in situ keratomileusis for high myopia.
AB  - We describe 2 women with high myopia of -12.0 and -18.0 diopters who presented
      with myopic macular hemorrhages 1 and 4 days, respectively, after being treated
      by laser in situ keratomileusis (LASIK). One hemorrhage was related to a pre
      existing choroidal neovascularization and the other to the presence of lacquer
      cracks. The hemorrhages resolved but resulted in a permanent decrease in vision.
      A careful fundus examination should be conducted before performing LASIK in
      highly myopic patients. In cases of similar macular pathology, fluorescein
      angiography should be done before LASIK.

PMID- 10889441
TI  - Delayed keratitis after laser in situ keratomileusis.
AB  - We report 2 cases of delayed keratitis that occurred after uneventful laser in
      situ keratomileusis (LASIK). The first patient presented with a peripheral
      corneal infiltrate 3 months after a LASIK enhancement procedure. The infiltrate
      progressed despite treatment with topical combination tobramycin-dexamethasone.
      The flap was then lifted and the interface was irrigated with fortified
      antibiotics. The keratitis promptly resolved, and the patient recovered a best
      corrected visual acuity (BCVA) of 20/20. The second patient presented with
      decreased vision, inflammation, and a sublamellar infiltrate 1 month after
      primary LASIK. The flap was promptly lifted and irrigated with antibiotics.
      Cultures were positive for Staphylococcus epidermidis. One week later, the
      infiltrate had resolved and BCVA had returned to 20/20. Delayed bacterial
      keratitis has been described as a rare occurrence after incisional refractive
      surgery. To the best of our knowledge, it has not yet been reported after LASIK.
      It is important to consider infectious keratitis in the differential diagnosis of
      a patient who presents with corneal inflammation, even months after having LASIK.

PMID- 10889442
TI  - Central and peripheral pressure measurements with the Goldmann tonometer and Tono
      Pen after photorefractive keratectomy for myopia.
AB  - To compare the accuracy of Goldmann tonometry with that of the Tono-Pen(R) in
      measuring intraocular pressure (IOP) after photorefractive keratectomy (PRK). Eye
      Clinic, Cantonal Hospital, Lucerne, Switzerland.Thirty-five eyes (25 patients)
      had PRK for a mean myopia of -6.2 diopters +/- 2.6 (SD). Intraocular pressure
      (IOP) measurements were performed first with the Goldmann tonometer and then with
      the Tono-Pen in 2 corneal locations: centrally in the usual manner and
      temporally. For the temporal measurements, the patient was directed to gaze
      nasally as the tonometer was placed perpendicular to the temporal portion of the
      cornea and with the rim of the tonometer positioned just inside the limbus of the
      cornea. Subsequently, similar measurements were made with the Tono-Pen.
      Measurements were performed before and 1 and 3 months after PRK. Preoperative
      IOPs measured centrally and temporally were similar. After PRK, the central
      pressure readings with the Goldmann tonometer and the Tono-Pen were between 1.8
      and 2.3 mm Hg lower than those measured temporally. The differences were
      statistically significant (P <.0001). Central corneal pressure readings obtained
      with either the Goldmann tonometer or the Tono-Pen after myopic PRK are
      inaccurate. Measurements over the temporal part of the cornea are likely more
      reliable.

PMID- 10889443
TI  - Acute suprachoroidal hemorrhage during phacoemulsification.
AB  - We present a case of acute suprachoroidal hemorrhage that developed during
      routine phacoemulsification in an 85-year-old patient after uneventful
      administration of periocular anesthesia. Pre-existing risk factors included
      advanced age, glaucoma, myopia, and hypertension. The scleral tunnel prevented
      major expulsion of intraocular contents; however, raised intraocular pressure
      prevented intraocular lens implantation. The rarity of this condition raises
      questions regarding the further management and precautions related to it.

PMID- 10889444
TI  - Complications of endocapsular tension ring implantation in a child with Marfan's
      syndrome.
AB  - A 4-year-old boy with Marfan's syndrome had severe visual impairment after
      subluxation of the crystalline lens with bisection of the pupil. In the first
      eye, a capsular tension ring and an intraocular lens (IOL) were uneventfully
      placed in the capsular bag after phacoemulsification. During implantation of the
      endocapsular tension ring in the second eye, an inadvertent tear of the anterior
      capsule occurred, and the posterior chamber IOL was placed in the sulcus. In both
      eyes, severe lens epithelial proliferation with secondary IOL decentration
      developed postoperatively. Several surgical revisions were necessary to keep the
      IOL within the optical axis. In the eye with the sulcus-implanted IOL, the
      endocapsular tension ring was markedly decentered.

PMID- 10889445
TI  - Glial cell type-specific responses to menadione-induced oxidative stress.
AB  - Glial cell types in the central nervous system are continuously exposed to
      reactive oxygen species (ROS) due to their high oxygen metabolism and demonstrate
      differential susceptibility to certain pathological conditions believed to
      involve oxidative stress. The purpose of the current studies was to test the
      hypothesis that mtDNA damage could contribute to the differential susceptibility
      of glial cell types to apoptosis induced by oxidative stress. Primary cultures of
      rat astrocytes, oligodendrocytes, and microglia were utilized, and menadione was
      used to produce the oxidative stress. Apoptosis was detected and quantitated in
      menadione-treated oligodendrocytes and microglia (but not astrocytes) using
      either positive annexin-V staining or positive staining for 3'-OH groups in DNA.
      The apoptotic pathway that was activated involved the release of cytochrome c
      from the intermitochondrial space and activation of caspase 9. Caspase 8 was not
      activated after exposure to menadione in any of the cells. Using equimolar
      concentrations of menadione, more initial damage was observed in mtDNA from
      oligodendrocytes and microglia. Additionally, using concentrations of menadione
      that resulted in comparable initial mtDNA damage, more efficient repair was
      observed in astrocytes compared to either oligodendrocytes or microglia. The
      differential susceptibility of glial cell types to oxidative damage and apoptosis
      did not appear related to cellular antioxidant capacity, because under the
      current culture conditions astrocytes had lower total glutathione content and
      superoxide dismutase activity than oligodendrocytes and microglia. These results
      show that the differential susceptibility of glial cell types to menadione
      induced oxidative stress and apoptosis appears to correlate with increased
      oxidative mtDNA damage and support the hypothesis that mtDNA damage could
      participate in the initiation of apoptosis through the enhanced release of
      cytochrome c and the activation of caspase 9.

PMID- 10889447
TI  - Hydrogen-peroxide-mediated catalase gene expression in response to wounding.
AB  - The effect of wounding on catalase expression was examined in embryos and leaves
      of maize. All three Cat genes are upregulated in response to wounding in immature
      embryos. Cat expression also increased in response to jasmonic acid (JA), raising
      the possibility that JA and wounding may share a common signal transduction
      pathway in upregulating Cat mRNA in immature embryos. In young leaves, only Cat1
      and Cat3 transcripts increase in response to wounding, but JA does not play a
      role. Cat1 and Cat3 transcript accumulation also increases in response to
      wounding in both wild-type and mutant leaves deficient in abscisic acid (ABA),
      implying that Cat1 and Cat3 induction in response to wounding is not mediated by
      ABA in leaves. Transient assays using the Cat1 promoter fused with the reporter
      gene Gus, showed that the DNA sequence motif responsible for Cat1 upregulation by
      wounding overlaps with the ABA-responsive element (ABRE, G-box) in the Cat1
      promoter. The exact nature of the signals triggering the Cat responses to
      wounding is not clear at this point, but some evidence indicates that reactive
      oxygen species (ROS) play a role in this response. In fact, we have found that
      endogenous H(2)O(2) levels increase in wounded leaves. Thus, wounding may
      indirectly induce the production of H(2)O(2) in leaves, triggering the
      antioxidant response.

PMID- 10889446
TI  - Acidic pH amplifies iron-mediated lipid peroxidation in cells.
AB  - The goal of our study was to investigate the mechanism by which changes in
      extracellular pH influence lipid peroxidation processes. Ferrous iron can react
      with hydroperoxides, via a Fenton-type reaction, to initiate free radical chain
      processes. Iron is more soluble at lower pH values, therefore we hypothesized
      that decreasing the environmental pH would lead to increased iron-mediated lipid
      peroxidation. We used Photofrin, a photosensitizer that produces singlet oxygen,
      to introduce lipid hydroperoxides into leukemia cells (HL-60, K-562, and L1210).
      Singlet oxygen reacts with the PUFA of cells producing lipid hydroperoxides.
      Using EPR spin trapping with POBN, free radical formation from HL-60 cells was
      only detected when Photofrin, light, and ferrous iron were present. Free radical
      formation increased with increasing iron concentration; in the absence of
      extracellular iron, radical formation was below the limit of detection and lipid
      hydroperoxides accumulated in the membrane. In the presence of iron, lipid
      derived radical formation in cells is pH dependent; the lower the extracellular
      pH (7.5-5.5), the higher the free radical flux; the lower the pH, the greater the
      membrane permeability induced in K-562 cells, as determined by trypan blue dye
      exclusion. These data demonstrate that lipid peroxidation processes, mediated by
      iron, are enhanced with decreasing extracellular pH. Thus, acidic pH not only
      releases iron from "safe" sites, but this iron will also be more damaging.

PMID- 10889448
TI  - Heme oxygenase activity causes transient hypersensitivity to oxidative
      ultraviolet A radiation that depends on release of iron from heme.
AB  - Heme oxygenase (HO) breaks down heme to iron, biliverdin, and carbon monoxide,
      and activity of this enzyme increases in many tissues and cell types after
      exposure to oxidative stress. There is evidence that increased HO activity is
      involved in long-term protective mechanisms against oxidative stress. We studied
      the effect of artificially overexpressed HO activity on the cytotoxicity of
      oxidative ultraviolet A (UVA) radiation after loading human cells with the HO
      substrate ferric heme (hemin). In contrast to the reported long-term protection
      attributed to HO activity, cells overexpressing HO activity were hypersensitive
      to UVA radiation shortly after heme treatment when compared with control cells.
      Cells overexpressing HO activity showed an increased rate of heme consumption and
      a higher level of accumulated free chelatable iron when compared with control
      cells. The hypersensitivity of cells overexpressing HO to UVA radiation after
      heme treatment was apparently caused by the increased accumulation of chelatable
      iron, because the iron chelator desferrioxamine strongly reduced the
      hypersensitivity. One day after the heme treatment, cells overexpressing HO
      activity were no longer hypersensitive to UVA radiation. We conclude that
      increased HO activity can temporarily increase the sensitivity of cells to
      oxidative stress by releasing iron from heme.

PMID- 10889449
TI  - Oxygen free radicals mediate the induction of manganese superoxide dismutase gene
      expression by TNF-alpha.
AB  - In this study, the hypothesis that oxygen free radicals act as intracellular
      messengers is examined. Treatment of human oral carcinoma SCC-25 cells with 200
      ng/ml human TNF-alpha for 6 h greatly increased manganese superoxide dismutase
      (MnSOD) gene expression as detected by western blotting, RT-PCR, and nuclear run
      on experiments. In the presence of the oxygen free radical spin trapping reagent,
      5,5-dimethyl pyrroline-N-oxide (DMPO), the induction of MnSOD gene expression by
      TNF-alpha was significantly reduced. Electron paramagnetic resonance experiments
      showed that the production of oxygen free radicals was enhanced in TNF-alpha
      treated cells. Taken together, these observations suggest that the induction of
      MnSOD expression by TNF-alpha is at least partially mediated by intracellular
      formation of oxygen free radicals, and that superoxide is most likely the
      initiating species involved in the mediation of MnSOD gene expression by TNF
      alpha.

PMID- 10889450
TI  - Indirect inhibition of mitochondrial dihydroorotate dehydrogenase activity by
      nitric oxide.
AB  - Dihydroorotate dehydrogenase (DHODH) catalyzes the oxidation of dihydroorotate to
      orotate in the pyrimidine biosynthesis pathway. It is functionally connected to
      the respiratory chain, delivering electrons to ubiquinone. We report here that
      inhibition of cytochrome c oxidase by nitric oxide (NO) indirectly inhibits DHODH
      activity. In digitonin-permeabilized cells, DEA/NO, a chemical NO donor, induced
      a dramatic decrease in DHO-dependent O(2) consumption. The inhibition was
      reversible and more pronounced at low O(2) concentration; it was correlated with
      a decrease in orotate synthesis. Since orotate is the precursor of all pyrimidine
      nucleotides, indirect inhibition of DHODH by NO may significantly contribute to
      NO-dependent cytotoxicity.

PMID- 10889451
TI  - Distribution of hydroxynonenal-modified proteins in the kainate-lesioned rat
      hippocampus: evidence that hydroxynonenal formation precedes neuronal cell death.
AB  - Decomposition of lipid peroxides gives rise to a wide range of aldehydes. 4
      Hydroxyalkenals and in particular 4-hydroxynonenal (HNE) are often the most toxic
      products. Frequently, it is unclear at which stage in the tissue injury process
      HNE is formed, i.e., is it a late stage or an early stage in which HNE
      contributes to subsequent cell death? The present study was carried out using an
      antibody to HNE-modified proteins to elucidate the time course and distribution
      of HNE in the lesioned hippocampus after kainate injections. HNE was absent from
      normal neurons, but dense staining to HNE was observed in degenerating neurons
      after kainate injection. The increase in HNE staining occurred as early as 1 d
      postinjection, at a time when there was no histological evidence of cell death.
      HNE immunoreactivity was observed in the degenerating CA1 and CA3 fields at 3 d
      and 1 week postinjection, but was confined to a cluster of neurons at the edge of
      the degenerating CA fields, at 2 and 3 weeks postinjection. These observations
      suggest that HNE formation is an early event after this tissue injury, and may
      contribute to later cell death.

PMID- 10889452
TI  - Mechanisms of hydrogen peroxide-induced calcium dysregulation in PC12 cells.
AB  - The mechanisms of H(2)O(2)-induced elevated calcium baselines in PC12 cells were
      investigated in the present study by using fura-2-fluorescent image analysis. The
      results showed that the calcium comes from both intracellular and extracellular
      sources. Although the major intracellular source was mitochondria, only the
      extracellular calcium influx was responsible for the sustained post-H(2)O(2)
      exposure increases. This calcium influx was partially blocked by calcium channel
      antagonists [verapamil (L-type) or mibefradil (nonselective)] and was more
      effectively blocked by the sodium channel antagonist, tetrodotoxin (TTX).
      Membrane depolarization following H(2)O(2) exposure contributed to the opening of
      the ion channels. The H(2)O(2)-induced calcium influx was blocked by TTX even in
      a sodium-free buffer, indicating that calcium directly fluxed through sodium
      channels. Sodium-calcium exchangers (NCX) on the plasma membrane did not play a
      role, because use of a specific reverse mode NCX inhibitor, No. 7943, was
      ineffective in blocking the influx. The H(2)O(2)-induced calcium influx was
      mimicked by using a thiol-selective oxidizing reagent, 2', 2'-dithiodipyridine,
      and in both situations, the calcium levels were completely reversed by a thiol
      selective reducing reagent, dithiothreitol. Our results indicated that mechanisms
      of oxidant-induced elevated calcium baselines in PC12 cells involved calcium
      influx through sodium and calcium channels that may be directly or indirectly
      attributed to thiol oxidation.

PMID- 10889453
TI  - Vascular oxidant stress early after balloon injury: evidence for increased
      NAD(P)H oxidoreductase activity.
AB  - Available evidence for oxidative stress after angioplasty is indirect or
      ambiguous. We sought to characterize the pattern, time course, and possible
      sources of free radical generation early after arterial balloon injury. Ex vivo
      injury performed in arterial rings in buffer with lucigenin yielded a massive
      oxygen-dependent peak of luminescence that decayed exponentially and was
      proportional to the degree of injury. Signals for injured vs. control arteries
      were 207. 1 +/- 17.9 (n = 13) vs 4.1 +/- 0.7 (n = 22) cpm x 10(3)/mg/min (p <.
      001). Data obtained with 0.25 mmol/l lucigenin were validated with 0. 005-0.05
      mmol/l lucigenin or the novel superoxide-sensitive probe coelenterazine (5
      micromol/l). Gentle removal of endothelium prior to injury scarcely affected the
      amount of luminescence. Lucigenin signals were amplified 5- to 20-fold by
      exogenous NAD(P)H, and were >85% inhibited by diphenyliodonium (DPI, a
      flavoenzyme inhibitor). Antagonists of several other potential free radical
      sources, including xanthine oxidase, nitric oxide synthase, and mitochondrial
      electron transport, were without effect. Overdistension of intact rabbit iliac
      arteries in vivo (n = 7) induced 72% fall in intracellular reduced glutathione
      and 68% increase in oxidized glutathione, so that GSH/GSSG ratio changed from
      7.93 +/- 2.14 to 0. 81 +/- 0.16 (p <.005). There was also 28.7% loss of the
      glutathione pool. Further studies were performed with electron paramagnetic
      resonance spectroscopy. Rabbit aortas submitted to ex vivo overdistension in the
      presence of the spin trap DEPMPO (5-diethoxy-phosphoryl-5-methyl-1-pyrroline-N
      oxide, 100 mmol/l, n = 5) showed formation of radical adduct spectra, abolished
      by DPI or superoxide dismutase. Computer simulation indicated a mixture of
      hydroxyl and carbon-centered radical adducts, likely due to decay of superoxide
      adduct. Electrical mobility shift assays for NF-kappaB activation were performed
      in nuclear protein extracts from intact or previously injured rabbit aortas.
      Balloon injury induced early NF-kappaB activation, which was decreased by DPI. In
      conclusion, our data show unambiguously that arterial injury induces an immediate
      profound vascular oxidative stress. Such redox imbalance is likely accounted for
      by activation of vessel wall NAD(P)H oxidoreductase(s), generating radical
      species potentially involved in tissue repair.

PMID- 10889454
TI  - Plasma antioxidants and longevity: a study on healthy centenarians.
AB  - A large body of experimental research indicates that oxidative stress contributes
      to the processes related to aging and to the pathogenesis of several age-related
      diseases. Vitamins and antioxidant enzymes have a fundamental role in defending
      the organism from oxidative stress. To better understand the role of antioxidants
      in human aging, we measured plasma levels of vitamin C (ascorbic acid), uric
      acid, vitamin E (alpha-tocopherol), vitamin A (retinol), carotenoids, total thiol
      groups, and the activity of plasma superoxide dismutase (SOD) and glutathione
      peroxidase (GPX) as well as the activity of red blood cell (RBC) SOD in 32
      healthy centenarians-17 elderly subjects aged 80-99 years, 34 elderly subjects
      aged 60-79 years, and 24 adults aged less than 60 years. Considering the
      "noncentenarians" only, we observed a consistent behavior in the antioxidant
      pattern, with a decrease of the nonenzymatic antioxidants and an increase of the
      enzymatic antioxidant activities relative to age. Remarkably, centenarians were
      characterized as having the highest levels of vitamins A and E, whereas the
      activities of both plasma and RBC SOD, which increase with age, decreased in
      centenarians. From these results, it is evident that healthy centenarians show a
      particular profile in which high levels of vitamin A and vitamin E seem to be
      important in guaranteeing their extreme longevity.

PMID- 10889455
TI  - Ferulic acid excretion as a marker of consumption of a French maritime pine
      (Pinus maritima) bark extract.
AB  - French maritime pine (Pinus maritima) bark extract (PBE) is a polyphenol-rich
      food supplement patented under the name of Pycnogenol and known to have strong
      antioxidant activity and different beneficial effects on human health. Although
      its biological properties have begun to be extensively studied both in vitro, in
      laboratory animals and more recently in humans, little is known about its
      bioavailability. The present study investigated the urinary excretion of free and
      conjugated ferulic acid, present in quantitatively detectable amounts in PBE,
      after oral PBE administration to human subjects. Eleven healthy adult subjects (4
      women and 7men) consumed either a single dose (200 mg PBE) or two doses of PBE
      (100 and 200 mg, respectively) within a 48-h interval. Two days before the oral
      administration of PBE and during the urine sample collection period volunteers
      adhered to a diet low in polyphenols. Aliquots of all urine production were
      collected over 24 h. Free and conjugated ferulic acid was assessed in urine by
      HPLC using diode array detection. A close association between the dietary intake
      of PBE and the urinary excretion of ferulic acid was detected. Moreover, the
      results indicate that a considerable proportion of ferulic acid is excreted as
      glucuronide or sulfate after PBE consumption, varying over the range 2 to 20%
      between individuals. The kinetics of excretion associated with the administration
      of 100 mg PBE was quite similar to that obtained after 200 mg PBE. A a biphasic
      trend was evident in a number of subjects. All subjects studied here displayed a
      significant, although variable level of excretion of ferulic acid after
      supplementation with PBE, Thus, the data provide evidence that at least a part of
      the phenolic components of PBE are absorbed, metabolized, and eliminated by
      humans.

PMID- 10889456
TI  - The effects of nitroxide radicals on oxidative DNA damage.
AB  - The indolinonic and quinolinic aromatic nitroxides synthesized by us are a novel
      class of biological antioxidants, which afford a good degree of protection
      against free radical-induced oxidation in different lipid and protein systems. To
      further our understanding of their antioxidant behavior, we thought it essential
      to have more information on their effects on DNA exposed to free radicals. Here,
      we report on the results obtained after exposure of plasmid DNA and calf thymus
      DNA to peroxyl radicals generated by the water-soluble radical initiator, 2,2'
      azobis(2-amidinopropane)dihydrochloride (AAPH), and the protective effects of the
      aromatic nitroxides and their hydroxylamines, using a simple in vitro assay for
      DNA damage. In addition, we also tested for the potential of these nitroxides to
      inhibit hydroxyl radical-mediated DNA damage inflicted by Fenton-type reactions
      using copper and iron ions. The commercial aliphatic nitroxides 2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPO), 4-hydroxy-2,2,6,6-tetramethylpiperidine-1
      oxyl (TEMPOL), and bis(2,2, 6,6-tetramethyl-1-oxyl-piperidin-4-yl)sebacate
      (TINUVIN 770) were included for comparison. The results show that the majority of
      compounds tested protect: (i) both plasmid DNA and calf thymus DNA against AAPH
      mediated oxidative damage in a concentration-dependent fashion (1-0.1 mM), (ii)
      both Fe(II) and Cu(I) induced DNA oxidative damage. However, all compounds failed
      to protect DNA against damage inflicted by the presence of the transition metals
      in combination with H(2)O(2). The differences in protection between the compounds
      are discussed in relation to their molecular structure and chemical reactivity.

PMID- 10889457
TI  - Redox-dependent trafficking of 2,3,4,5, 6-pentafluorodihydrotetramethylrosamine,
      a novel fluorogenic indicator of cellular oxidative activity.
AB  - The trafficking of 2,3,4,5,6-pentafluorodihydrotetramethylrosamine (PF-H(2)TMRos,
      also known as RedoxSensor Red), a new fluorogenic indicator for oxidative
      activity, was evaluated in a contact-inhibited cell line, normal rat kidney
      fibroblast (NRK-49F), using quantitative fluorescence microscopy. After cells
      were incubated with 1-5 microM dye at 37 degrees C for 10 to 30 min, fluorescent
      staining of its oxidized product (PF-TMRos) distributed in mitochondria and/or
      lysosomes. This distribution pattern varied depending on the proliferation state
      of cells. In proliferating cells, PF-H(2)TMRos was internalized through a
      nonendocytic pathway, then oxidized in the cytosol, followed by immediate
      targeting to active mitochondria, resulting in fluorescent staining in this
      organelle. Photo-oxidation experiments demonstrated that PF-H(2)TMRos is not
      directly transported to mitochondria. On the contrary, in contact-inhibited cells
      whose proliferation is inhibited, PF-H(2)TMRos enters cells and is transported to
      lysosomes before it is oxidized. This results in lysosomal rather than
      mitochondrial staining. In both proliferating and quiescent cell states,
      subcellular distribution of the oxidized dye PF-TMRos can be altered by treatment
      with an oxidant (hydrogen peroxide) or an antioxidant (N-acetyl-L-cysteine),
      indicating a regulatory relationship between cell proliferation and oxidative
      activity. In solution assay, this probe can be oxidized by a broad spectrum of
      oxidizing species including horseradish peroxidase, hydrogen peroxide and
      horseradish peroxidase, cytochrome c, cytochrome c and hydrogen peroxide,
      superoxide and hydrogen peroxide, nitric oxide (or nitrite), peroxynitrite, and
      lipid hydroperoxide. Based on its subcellular distribution and its oxidation by a
      broad range of oxidizing species, PF-H(2)TMRos is demonstrated to be a novel
      indicator for cellular oxidative stresses.

PMID- 10889458
TI  - Effect of long-term cold exposure on antioxidant enzyme activities in a small
      mammal.
AB  - Aerobic organisms continually face exposure to reactive oxygen species (ROS) and
      many have evolved sophisticated antioxidant systems to effectively remove them.
      Any increase in ROS production or weakening in this defense system may ultimately
      lead to oxidative stress and cellular damage. We investigated whether long-term
      cold exposure, which is known to lead to an elevation in metabolic rate,
      increased the activities of the ROS-scavenging enzymes, catalase (CAT), selenium
      dependent glutathione peroxidase (GPx), and total superoxide dismutase (Total
      SOD) in liver, cardiac muscle, kidney, skeletal muscle (vastus lateralis), and
      duodenum of short-tailed field voles (Microtus agrestis), born and maintained at
      either 8 +/- 3 degrees C or 22 +/- 3 degrees C. CAT, GPx, and Total-SOD
      activities were determined at age 61 +/- 1.9 days. An increase in CAT activity in
      voles maintained at 8 +/- 3 degrees C was observed in skeletal muscle (71%) and
      kidney (20%), with both CAT and GPx activities significantly elevated (by 40 and
      43%, respectively) in cardiac muscle, when compared to voles at 22 +/- 3 degrees
      C. Total-SOD activity and protein content did not differ significantly between
      groups in any tissue. We suggest that the compensatory increases in CAT (skeletal
      muscle, cardiac muscle, kidney) and GPx (cardiac muscle), but not Total-SOD
      activities, resulting from long-term cold exposure may reflect the elevated
      metabolic rate, and possibly also increased ROS production, at this time.

PMID- 10889459
TI  - H(2)O(2) and PARS mediate lung P-selectin upregulation in acute pancreatitis.
AB  - P-selectin and circulating xanthine oxidase are involved in the process of
      neutrophil infiltration into the lung associated with acute pancreatitis. This
      study investigated the mediators that trigger the upregulation of P-selectin in
      this process. Pancreatitis was induced in rats by intraductal administration of
      5% sodium taurocholate. P-selectin expression was measured using radiolabeled
      antibodies. Neutrophil infiltration and PAF levels were also evaluated. The role
      of superoxide radical, H(2)O(2), or the enzyme poly (ADP-ribose) synthetase
      (PARS) on these processes was determined in groups of animals treated with the
      corresponding inhibitors. Pancreatitis was associated with an increase in P
      selectin expression in the lung. Inhibition of PARS or H(2)O(2) abrogated P
      selectin upregulation, PAF generation, and neutrophil recruitment. Superoxide
      dismutation prevented neutrophil recruitment and PAF generation, but had no
      effect on P-selectin expression. We conclude that during acute pancreatitis,
      upregulation of P-selectin in the pulmonary endothelium is triggered by H(2)O(2)
      and PARS activity.

PMID- 10889460
TI  - Asbestos and cigarette smoke cause increased DNA strand breaks and necrosis in
      bronchiolar epithelial cells in vivo.
AB  - Coexposures to asbestos and cigarette smoke cause increased risks of lung cancer
      in asbestos workers. Although these carcinogens cause DNA damage to epithelial
      cells in vitro via generation of reactive oxygen species (ROS), it is unclear
      whether they cause injury to bronchiolar epithelial cells (i.e., the target cells
      of lung cancers in vivo). We exposed rats to amosite asbestos, cigarette smoke,
      and the two agents in combination for 1, 2, and 14 d. Numbers of cells exhibiting
      DNA strand breaks in comparison to sham rats were then evaluated in lungs using
      the terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-biotin nick end
      labeling (TUNEL) method and by transmission electron microscopy (TEM). Increases
      in TUNEL-positive, necrotic epithelial cells occurred after exposure to asbestos
      alone and in an additive fashion after smoke and asbestos in combination. These
      results indicate that DNA strand breakage and necrosis are prominent mechanisms
      of injury by asbestos fibers and cigarette smoke in vivo to epithelial cells of
      the respiratory tract, thus validating in vitro observations from a number of
      laboratories.

PMID- 10889461
TI  - NMDA receptor activation: critical role in oxidant tissue injury.
AB  - The excitatory amino acid glutamate serves important neurologic functions, but
      overactivation of its N-methyl-D-aspartate (NMDA) receptor is toxic to neurons
      (excitotoxicity). We report that NMDA receptor blocker MK-801 (dizocilpine
      maleate) attenuated oxidant injury induced by paraquat or by xanthine oxidase. We
      conclude that excitotoxicity may be a key factor in oxidant tissue injury.

PMID- 10889462
TI  - Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1
      and protects endothelial cells against oxidative stress.
AB  - Curcumin, a widely used spice and coloring agent in food, has been shown to
      possess potent antioxidant, antitumor promoting and anti-inflammatory properties
      in vitro and in vivo. The mechanism(s) of such pleiotropic action by this yellow
      pigment is unknown; whether induction of distinct antioxidant genes contributes
      to the beneficial activities mediated by curcumin remains to be investigated. In
      the present study we examined the effect of curcumin on endothelial heme
      oxygenase-1 (HO-1 or HSP32), an inducible stress protein that degrades heme to
      the vasoactive molecule carbon monoxide and the antioxidant biliverdin. Exposure
      of bovine aortic endothelial cells to curcumin (5-15 microM) resulted in both a
      concentration- and time-dependent increase in HO-1 mRNA, protein expression and
      heme oxygenase activity. Hypoxia (18 h) also caused a significant (P < 0.05)
      increase in heme oxygenase activity which was markedly potentiated by the
      presence of low concentrations of curcumin (5 microM). Interestingly, prolonged
      incubation (18 h) with curcumin in normoxic or hypoxic conditions resulted in
      enhanced cellular resistance to oxidative damage; this cytoprotective effect was
      considerably attenuated by tin protoporphyrin IX, an inhibitor of heme oxygenase
      activity. In contrast, exposure of cells to curcumin for a period of time
      insufficient to up-regulate HO-1 (1.5 h) did not prevent oxidant-mediated injury.
      These data indicate that curcumin is a potent inducer of HO-1 in vascular
      endothelial cells and that increased heme oxygenase activity is an important
      component in curcumin-mediated cytoprotection against oxidative stress.

PMID- 10889463
TI  - Advances in signalling by extracellular nucleotides. the role and transduction
      mechanisms of P2Y receptors.
AB  - Nucleotides are ubiquitous intercellular messengers whose actions are mediated by
      specific receptors. Since the first clonings in 1993, it is known that nucleotide
      receptors belong to two families: the ionotropic P2X receptors and the
      metabotropic P2Y receptors. Five human P2Y receptor subtypes have been cloned so
      far and a sixth one must still be isolated. In this review we will show that they
      differ by their preference for adenine versus uracil nucleotides and triphospho
      versus diphospho nucleotides, as well as by their transduction mechanisms and
      cell expression.

PMID- 10889464
TI  - Cellular "sensing" of extracellular calcium (Ca(2+)(o)): emerging roles in
      regulating diverse physiological functions.
AB  - The extracellular Ca(2+) (Ca(2+)(o))-sensing receptor (CaR) critically influences
      Ca(2+)(o) homeostasis by regulating parathyroid hormone (PTH) secretion and renal
      Ca(2+) handling. Moreover, its expression in intestinal and bone cells suggests
      roles in all of the organs involved in maintaining systemic Ca(2+)(o)
      homeostasis. This G-protein coupled receptor is also expressed in a wide variety
      of additional cells throughout the body. While our understanding of its role(s)
      outside of the system governing Ca(2+)(o) metabolism remains rudimentary, the CaR
      will probably emerge as a versatile regulator of diverse cellular functions,
      including proliferation, differentiation, apoptosis, gene expression and
      maintenance of membrane potential. Finally, the recently developed,
      "calcimimetic" CaR activators, exemplified by a NPS R-467 and NPS R-568, provide
      novel approaches to treating diseases that previously had no effective medical
      therapies: topic likewise covered in this review.

PMID- 10889465
TI  - Activation of the interleukin 2 receptor: a possible role for tyrosine
      phosphatases.
AB  - Engagement of interleukin-2 (IL-2) mediates the heterodimeridation of the common
      beta chain (beta(c)) and common gamma chain (gamma(c)) of the IL-2 receptor (IL
      2R). This is sufficient and necessary for receptor activation and signal
      transduction. It is generally held that the IL-2R is activated by the trans
      activity of the protein tyrosine kinases (PTKs) Jak1 and Jak3 associated with
      beta(c) and gamma(c) respectively. Transduction of proliferative signals requires
      Jak3 activity. A Jak3 independent signalling pathway involving p56(lck),
      generating anti-apoptotic signals, can be observed and requires the PROX domain
      of gamma(c). p56(lck) can be activated by dephosphorylation of an inhibitory
      carboxyl terminal phosphorylated tyrosine residue (Y505). We propose that this is
      mediated by a PROX domain associated protein tyrosine phosphatase (PTP).
      Activation of p56(lck) alone is insufficient for transduction of proliferative
      signals and thus works in concert with Jak3 mediated receptor activation. This
      indicates that both gamma(c) domains are vital for signal transduction.

PMID- 10889466
TI  - Endothelin-1 induces vascular endothelial growth factor synthesis in osteoblasts:
      involvement of p38 mitogen-activated protein kinase.
AB  - We previously reported that endothelin-1 (ET-1) stimulates p44/p42 mitogen
      activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1
      cells. In the present study, we investigated the effect of ET-1 on the synthesis
      of vascular endothelial growth factor (VEGF) in these cells. ET-1 significantly
      stimulated VEGF secretion time-dependently 18 hours after the stimulation. The
      stimulatory effect was dose-dependent in the range between 0.1 nM and 0.1
      micro;M. BQ123, an antagonist of endothelin(A) (ET(A)) receptor, inhibited the ET
      1-induced VEGF secretion. The ET-1-induced VEGF secretion was suppressed by
      SB203580 and PD169316, inhibitors of p38 MAP kinase, but not PD98059, an
      inhibitor of the upstream kinase that activates p44/p42 MAP kinase. 12-O
      Tetradecanoylphorbol-13-acetate (TPA), a protein kinase C (PKC)-activating
      phorbol ester, stimulated VEGF secretion. Calphostin C, a specific PKC inhibitor,
      suppressed the VEGF secretion by ET-1. TPA-induced VEGF secretion was suppressed
      by SB203580. Taken together, our results strongly suggest that ET-1 stimulates
      VEGF synthesis via ET(A) receptor in osteoblasts and that p38 MAP kinase is
      involved at a point downstream from PKC in the VEGF synthesis.

PMID- 10889467
TI  - Mkp1 of Pneumocystis carinii associates with the yeast transcription factor Rlm1
      via a mechanism independent of the activation state.
AB  - The mitogen-activated protein (MAP) kinase Mkp1 of the fungal pathogen
      Pneumocystis carinii is a functional MAP kinase that complements the loss of
      Slt2p, the MAP kinase component of the cell integrity pathway of Saccharomyces
      cerevisiae, and is activated within P. carinii in response to oxidative stress.
      Mkp1 displays an unusual feature in that it contains a phosphorylation motif
      repeat (TEYMTEY) within the activation loop not present in any other fungal MAPK
      identified to date. Mutagenesis of the T186,Y188 phosphorylation motif within the
      activation domain of Mkp1 results in the loss of detectable kinase activity but
      still retains partial complementation function. In addition to the ability of
      Mkp1 to restore partial activity to the cell integrity pathway in the absence of
      phosphorylatable residues within the activation loop, the association of Mkp1
      with a substrate of Slt2p, the transcription factor Rlm1p, can also occur in the
      absence of MAP kinase activation. The results of this study suggest that the
      presence of phosphorylatable residues within the activation loop of Mkp1 is not
      absolutely required for functional (complementation) activity or for the
      association of Mkp1 with the transcription factor Rlm1p. In contrast, the
      catalytic lysine of the ATP-binding domain of Mkp1 is necessary for both
      complementation function and interaction with Rlm1p.

PMID- 10889468
TI  - Studies on fMLP-receptor interaction and signal transduction pathway by means of
      fMLP-OMe selective analogues.
AB  - For-Thp-Leu-Ain-OMe ([Thp(1), Ain(3)] fMLP-OMe) (2), for-Met-delta(z)Leu-Phe-OMe
      ([delta(z)Leu(2)] fMLP-OMe) (3), for-Thp-Leu-Phe-OMe ([Thp(1)] fMLP-OMe) (4), and
      for-Met-Leu-Ain-OMe ([Ain(3)] fMLP-OMe) (5) are for-Met-Leu-Phe-OMe (fMLP-OMe)
      (1) analogues which discriminate between different responses of human
      neutrophils. Peptides 3 and 5, similar to fMLP-OMe, enhance neutrophil cyclic AMP
      (cAMP) as well as calcium levels, while analogues 2 and 4, which evoke only
      chemotaxis, do not alter the concentration of these intracellular messengers.
      When we tested the peptides' ability to displace [3H]-fMLP from its binding
      sites, the following order of potency was observed: analogue 1 > 3 > 5 > 2 > 4. A
      particularly low activity at the receptor level characterized analogues 2 and 4.
      Their low effectiveness was not improved by the addition of cytochalasin B, by
      different incubation temperatures, or by the absence of endogenous guanine
      nucleotides, conditions known to influence fMLP receptor fate and functionality.
      We speculate that, in certain conditions, the fMLP receptor may undergo
      conformational changes that impede the binding of pure chemoattractants.

PMID- 10889469
TI  - Different regulation of phospholipase D activity in glioma C6 cells by
      sphingosine, propranolol, imipramine and phorbol ester.
AB  - In has been found that sphingosine, propranolol, imipramine and phorbol ester (12
      O-tetradecanoylphorbol-13-acetate, TPA) have a stimulatory effect on
      phospholipase D activity in glioma C6 cells. The cells were prelabelled with [1
      (14)C]palmitic acid and phospholipase D-mediated synthesis of
      [(14)C]phosphatidylethanol was measured. The enhancing effect of TPA was almost
      completely blocked by a specific protein kinase C inhibitor, GF 109203X. In
      contrast, GF 109203X failed to inhibit the sphingosine, imipramine and
      propranolol stimulatory effects, indicating that their stimulation was
      independent of protein kinase C. The effect of TPA on phospholipase D was also
      blocked by imipramine and propranolol, whereas sphingosine additively potentiated
      TPA-mediated phospholipase D activity, both at shorter and longer (2-60 min)
      times of incubation. These results suggest that in glioma C6 cells, sphingosine
      is not only involved in a different phospholipase D activation than the TPA
      regulatory system, but also that it operates in a different compartment of the
      cell.

PMID- 10889470
TI  - The permissive effect of p21(Waf1/Cip1) on DNA synthesis is dependent on cell
      type: effect is absent in p53-inactive cells.
AB  - The cyclin-dependent kinase inhibitors (CKI) interact with cyclin-cdk complexes
      to arrest mitogen-stimulated transit through the cell cycle, but we and others
      have recently shown that these molecules can exert permissive effects on cell
      cycle transit as well. The p53 protein induces transcription of the
      p21(Waf1/Cip1) gene, but whether p53 has any effect on the stimulatory versus
      inhibitory state of p21(Waf1/Cip1) toward cell growth is not known. The focus of
      the current study was to examine the effect of p21(Waf1/Cip1) inhibition on
      growth in cells which possess an inactive p53 protein. We found that there was
      significant and specific inhibition of p21(Waf1/Cip1) protein transcription in
      human squamous carcinoma A431 cells after transfection of an antisense
      p21(Waf1/Cip1) oligodeoxynucleotide, yet there was no significant growth
      inhibition in these cells after stimulation with 10% serum or with PDGF-BB, in
      contrast to what was observed in vascular smooth muscle (VSM) cells. Furthermore,
      there was no attenuation of either cyclinD/cdk4 association or of Rb
      hyperphosphorylation after antisense p21(Waf1/Cip1) oligodeoxynucleotide
      transfection, suggesting that an alternate pathway exists to allow association
      and phosphorylation of these cell cycle components in the absence (or with lower
      levels) of p21(Waf1/Cip1). Thus, the permissive effect of p21(Waf1/Cip1) toward
      growth is dependent on cell type, and active p53 is likely required for this
      effect.

PMID- 10889471
TI  - The carcinogen Cd(2+) activates InsP(3)-mediated Ca(2+) release through a
      specific metal ion receptor in Xenopus oocyte.
AB  - The effects of the carcinogen Cd(2+) on Xenopus oocyte were evaluated by Inositol
      (1,4,5)-trisphosphate (InsP(3)) assays and electrophysiological experiments. The
      stimulation of the Ca(2+)-dependent Cl(-) current by Cd(2+) is clearly linked to
      InsP(3) formation since the effects of the metal are antagonized by neomycin,
      heparin and caffeine. A similar inhibition of the Cd(2+) effects is observed when
      the oocytes are pretreated with thapsigargin. Moreover, the use of sulfhydryl
      groups reductors such as 2-mercaptoethanol or N-ethylmaleimide strongly suggests
      that the Cd(2+) response is mediated by an extracellular receptor. Finally,
      measurements of InsP(3) production demonstrate that Cd(2+) superfusion actually
      leads to a PIP(2) breakdown. We conclude that extracellular Cd(2+) evokes an
      increase in [Ca(2+)](i) by stimulating the emptying of the InsP(3)-sensitive
      Ca(2+) stores, and that it may do so by interacting with a specific cell-surface
      ion receptor. This putative ion receptor may be important in allowing oocytes to
      respond to heavy metals.

PMID- 10889472
TI  - First place--resident basic science award 1999. Effects of leukotriene and cyclo
      oxygenase inhibition on adaptive bone remodeling in the middle ear.
AB  - Abnormal bone remodeling is associated with important otolaryngologic diseases.
      In such diseases, the mechanisms of osteoclastic control underlie the pathologic
      processes. It is known that strain applied to auditory bullae induces bone
      resorption-an effect mediated by prostaglandins and blocked by cyclo-oxygenase
      inhibitors. It is also known that cyclo-oxygenase inhibition shunts arachidonic
      acid into alternate metabolic pathways, mainly the lipoxygenase pathway with
      leukotriene production. The role of these metabolites in adaptive bone remodeling
      is unknown. Using the gerbilline bulla as a model, we infused BW755c (dual
      lipoxygenase/cyclo-oxygenase inhibitor) and L-663,536 (5-lipoxygenase inhibitor)
      into animals undergoing middle ear pressurization. After 7 days, the bulla bones
      were harvested, and osteoclasts were quantified histomorphometrically. The
      results showed that neither treatment altered pressure-induced resorption.
      However, BW755c significantly increased resorption in unpressurized bone when
      compared with control values. Because BW775c blocks both lipoxygenase and cyclo
      oxygenase pathways, the results suggest an alternate pathway in middle ear bone
      resorption.

PMID- 10889473
TI  - First place--resident clinical science award 1999. Quality of life for children
      with obstructive sleep apnea.
AB  - The caregivers of 61 eligible children (6 months to 12 years old) completed a 20
      item (OSA-20) health-related quality-of-life survey after polysomnography was
      performed to psychometrically validate the OSA-20. Excellent test-retest
      reliability was obtained for the individual survey items (R>0.74). Construct
      validity was shown by significant correlation of the mean survey score with the
      respiratory distress index (R = 0.43) and adenoid size (R = 0.43). Two items with
      poor validity were dropped, reducing the survey to 18 items (OSA-18). The
      relationship between the OSA-18 summary score and respiratory distress index
      remained significant when adjusted for tonsil size, adenoid size, body mass
      index, and child age. On the basis of the total survey score, the impact of OSAS
      on quality of life was small for 20 children (33%), moderate for 19 (31%), and
      large for 22 (36%). The OSA-18 is a practical means of office-based determination
      of quality-of-life impact for obstructive sleep apnea syndrome in children.

PMID- 10889474
TI  - Tympanic membrane perforation repair using AlloDerm.
AB  - BACKGROUND: Some patients lack quality autologous tissue for tympanic membrane
      (TM) grafting. AlloDerm (LifeCell Corp, The Woodlands, TX) is a preserved
      allograft that has been effective in nonotologic applications. OBJECTIVE: The
      goal of this study was to investigate AlloDerm in the repair of chronic TM
      perforations. METHODS: Ten adult chinchillas underwent a controlled, 2-stage
      procedure for creation and repair of bilateral TM perforations. Myringoplasties
      were performed. The control side (left) was repaired with autologous fascia;
      AlloDerm was used in all right ears. Grafts were assessed at 3 to 8 weeks.
      RESULTS: Complete TM perforation closure was noted in 9 of 10 (90%) control ears
      and 8 of 10 (80%) AlloDerm-treated ears. Fascia and AlloDerm integrated
      consistently with host tissues. No variables demonstrated statistical
      significance. CONCLUSIONS: AlloDerm appeared to be an ideal substitute for
      grafting of the TM. It was equally effective as fascia. Clinical trials in human
      beings appear warranted. Potential health care savings are discussed.

PMID- 10889475
TI  - Effects of vestibular and cerebellar deficits on gaze and torso stability during
      ambulation.
AB  - We measured gaze, head, and torso stability during ambulation to determine how
      vestibulo-ocular reflex dysfunction caused by unilateral vestibulopathy,
      bilateral vestibulopathy, and cerebellar dysfunction might affect image
      stabilization on the retina. Subjects were tested during standing, walking, and
      running on a treadmill. Gaze velocity, vestibulo-ocular reflex gain, and head
      velocities were calculated from angular positions of the eye and head, as well as
      linear positions of the head and trunk. Mean gaze velocity with a visible,
      distant target was below 4 degrees /second for all measurement conditions in
      control and vestibulopathic subjects. The performance of unilaterally
      vestibulopathic subjects was indistinguishable from that of control subjects
      except that the former had less vertical translation during walking. Bilaterally
      vestibulopathic subjects demonstrated less head translation than control subjects
      but had higher gaze velocity. In subjects with cerebellar dysfunction, gaze
      velocity was elevated by pathologic nystagmus, but head movements were similar to
      those of control subjects.

PMID- 10889476
TI  - Otolaryngology-Head and Neck Surgery moving into the millennium: The changing of
      the guard.

PMID- 10889477
TI  - Ossiculoplasty in canal wall down mastoidectomy.
AB  - OBJECTIVE: The aim of this study was to evaluate the initial and longer term
      success of closing the air-bone gap (ABG) to 20 dB in ossiculoplasty with canal
      wall down mastoidectomy. METHODS: This study was conducted at a private otologic
      practice. Patients included those who underwent ossiculoplasty from 1989 to 1996
      with canal wall down mastoidectomy, whether primary or revision (33 from a total
      of 387 tympanomastoidectomies). Outcome measures included ABG closure, long-term
      hearing stability, mastoid appearance, extrusion, and sensorineural hearing loss.
      RESULTS: Almost 64% of ABGs were closed to within 20 dB. The mean pure-tone
      average improvement was 12.3 dB. The mean PTA hearing decline in the years after
      surgery was slightly less than 1 dB/year. CONCLUSION: Hearing improvement with a
      stable long-term hearing result is possible with canal wall down mastoidectomy.
      The potential for hearing gain is greatest for patients having larger
      preoperative ABGs.

PMID- 10889478
TI  - Endoscopic optic nerve decompression for traumatic blindness.
AB  - OBJECTIVES: The goal of this study was to compare the outcome of patients with
      traumatic optic neuropathy (TON) treated with high-dose steroids with the outcome
      of patients with TON treated with endoscopic optic nerve decompression (EOND)
      after failing high-dose steroid treatment. METHODS: During this retrospective
      review of patients with TON seen from 1994 to 1998, all patients were first
      treated with megadose methylprednisolone for 48 hours. Patients with no
      improvement or with worsening visual acuity were offered EOND. RESULTS: Eleven of
      34 (32%) patients treated with high-dose steroids showed improvement, and 23
      (68%) did not. Seventeen of the 23 patients without improvement after high-dose
      steroid treatment underwent EOND. Fourteen of 17 (82%) surgically treated
      patients had improved visual acuity, and 3 (18%) did not, with an overall
      improvement in 25 of 34 (74%) patients (chi(2) = 11. 338, P = 0.0007).
      CONCLUSION: EOND is an appropriate treatment technique for patients with TON in
      whom high-dose steroid treatment has failed.

PMID- 10889479
TI  - Videostroboscopy of the pharyngoesophageal segment in laryngectomy patients
      treated with botulinum toxin.
AB  - OBJECTIVES: The purpose of this investigation was to use videostroboscopy to
      study the physiologic and biomechanical effects of botulinum toxin (Botox)
      injection on the pharyngoesophageal segment (PES) in total laryngectomy patients
      with poor-quality tracheoesophageal puncture (TEP) voice caused by PES spasm.
      METHODS: The following was a prospective study. Videostroboscopy of the PES and
      videotaped recordings of patients performing TEP voice tasks were conducted
      before and after Botox injection of the PES. Ratings of videostroboscopic and
      speech samples were performed by 3 blinded judges with extensive experience with
      this patient population. RESULTS: Perceptually, TEP voice was more fluent and
      less strained after injection. Videostroboscopically, patients demonstrated
      improved PES volitional control and mucosal wave characteristics after Botox
      injection. CONCLUSION: Botox injection in total laryngectomy patients with poor
      quality TEP voice caused by PES spasm provides improved physiologic and
      biomechanical function of the PES, as demonstrated for the first time
      videostroboscopically. These findings help explain the perceptual ratings of TEP
      voice improvement noted after Botox injection. Videostroboscopy can be used to
      provide diagnostic information to help confirm the clinical impression of PES
      spasm, as well as to document the effects of Botox injection on PES function.

PMID- 10889480
TI  - Quantification of rebound edema after steroid treatment.
AB  - OBJECTIVE: Return of edema after abrupt discontinuation of steroid treatment has
      never been studied or quantified. The purpose of this study was to measure the
      effect of abrupt cessation and tapering doses of steroids on tissue water content
      (TWC) in a rat skin flap model. DESIGN: A randomized controlled animal trial was
      designed to study the effects of discontinuation of steroid on skin flap edema.
      The animals were assigned to a control group (C), a steroid group (S), an abrupt
      steroid cessation (SC) group, or a tapering steroid (ST) group. MAIN OUTCOME
      MEASURES: In each group the skin flaps were biopsied at 30 and 36 hours. TWC was
      determined by a biopsy-drying technique. RESULTS: A significant difference (P =
      0.05) was found between the C and S groups and between the SC and S groups at
      both 30 and 36 hours, with the C group having the highest TWC. No significant
      difference was noted between the SC and C groups. The ST group had significantly
      less edema than the C group and similar TWC to that of the S group. CONCLUSION:
      Edema rebounded in the skin flaps after abrupt cessation of steroids (SC was not
      different from C), presumably because of destabilization of inflammatory
      mediators. The rebound effect was not observed in the ST group. The control of
      rebound edema by a tapering steroid protocol may be important in skin flap
      survival and may have implications for the management of airway edema.

PMID- 10889481
TI  - Treatment of delayed food allergy based on specific immunoglobulin G RAST
      testing.
AB  - This preliminary, descriptive study after extensive clinical experience
      demonstrates specific IgG food RASTs done in 114 consecutive patients with strong
      positive histories for delayed food allergy. Elimination of the positive foods
      was the sole means of treatment. The symptoms leading to the test are detailed,
      and the method of workup is reviewed. The overall results demonstrated a 71%
      success rate for all symptoms achieving at least a 75% improvement level. Of
      particular interest was the group of patients with chronic, disabling symptoms,
      unresponsive to other intensive treatments. Whereas 70% obtained 75% or more
      improvement, 20% of these patients obtained 100% relief.

PMID- 10889482
TI  - Cautery-assisted palatal stiffening operation for the treatment of obstructive
      sleep apnea syndrome.
AB  - Cautery-assisted palatal stiffening operation (CAPSO) is a recently developed
      single office-based procedure performed with local anesthesia for the treatment
      of palatal snoring. A midline strip of soft palate mucosa is removed, and the
      wound is allowed to heal by secondary intention. The flaccid palate is stiffened,
      and palatal snoring ceases. This prospective study evaluated the ability of CAPSO
      to treat obstructive sleep apnea syndrome (OSAS). Twenty-five consecutive
      patients with OSAS underwent CAPSO. Responders were defined as patients who had a
      reduction in apnea-hypopnea index (AHI) of 50% or more and an AHI of 10 or less
      after surgery. By these strict criteria, 40% of patients were considered to have
      responded to CAPSO. Mean AHI improved from 25.1+/-12.9 to 16.6+/-15.0 (P =
      0.010). The Epworth Sleepiness Scale, a subjective measure of daytime sleepiness,
      improved from 12.7+/-5.6 to 8.8+/-4.6 (P<0.001). These results indicate that
      CAPSO is as effective as other palatal surgeries in the management of OSAS.

PMID- 10889483
TI  - Acoustic rhinometry and computed tomography scans for the diagnosis of nasal
      septal deviation, with clinical correlation.
AB  - OBJECTIVE: The aim in this study was to analyze the efficiency and reliability of
      acoustic rhinometry (AR) readings in recognition of nasal septal deviation.
      METHOD: We compared 24 patients' AR readings with their sinus CT scans. The
      patient data were analyzed by comparison with normative data, area, and
      percentage differences between the two sides. Additionally, the data further
      analyzed by receiver operating characteristic curve and Spearman correlation of
      CT and AR in determining nasal septal deviation. RESULTS: The sensitivity of AR
      in detecting anterior septal deviations was found to be 54%, with a specificity
      of 70%. A very highly significant correlation (P < or = 0.001) was found between
      minimal cross-sectional area (CSA) 1 values and CT results. DISCUSSION: In the
      interpretation of AR readings, comparison of each CSA value should be included,
      in addition to use of the total absolute CSA values. CONCLUSION: According to our
      findings the diagnosis of nasal septal deviation can be supported by AR readings.

PMID- 10889484
TI  - Prevalence of allergy in Meniere's disease.
AB  - OBJECTIVES: The goal of this study was to determine the prevalence of allergy in
      a population of patients with Meniere's disease. METHODS: A survey was mailed to
      all patients with Meniere's disease seen at our institution from 1994 to July
      1998 (n = 1490). As a control group, 172 patients with otologic problems other
      than Meniere's disease completed the same survey. RESULTS: Of 734 respondents
      with Meniere's disease, 59.2% reported possible airborne allergy, 40.3% had or
      suspected food allergies, and 37% had had confirmatory skin or in vitro tests for
      allergy. These prevalence rates were significantly higher than those found in the
      control group, of which 42.7% reported having or suspecting airborne allergies
      and 25% had or suspected food allergies (differences all significant at P< or
      =0.005). CONCLUSION: The prevalence of allergy appears to be much higher in
      patients with Meniere's disease than in the general population or the population
      of patients visiting an otologic clinic for other symptoms.

PMID- 10889485
TI  - Middle turbinate medialization and preservation in endoscopic sinus surgery.
AB  - OBJECTIVE/HYPOTHESIS: Lateral synechia formation between the middle turbinate
      (MT) and the lateral nasal wall is the most common complication of endoscopic
      sinus surgery. In an attempt to prevent this complication, a simple technique to
      preserve and medialize the MT was studied. METHODS: Five hundred patients
      underwent endoscopic sinus surgery with MT medialization and preservation. The
      caudal end of the MT and the opposing septal mucosa were abraded with a
      microdebrider for controlled synechia formation in an attempt to avoid
      lateralization of the MT. Follow-up ranged from 6 to 18 months, with a mean
      follow-up of 10 months. RESULTS: Ninety-three percent of the patients had
      successful MT medialization with a well-defined synechia between the septum and
      the MT. CONCLUSIONS: MT medialization with a microdebrider is simple, is
      reliable, and should be considered an alternative to turbinate resection or to
      other turbinate medialization techniques.

PMID- 10889486
TI  - Does the severity of sinus computed tomography findings predict outcome in
      chronic sinusitis?
AB  - OBJECTIVES: We studied the association between the severity of pretreatment CT
      scan findings and the improvement in symptoms of chronic sinusitis after
      treatment. METHODS: We analyzed data from an ongoing prospective, nonrandomized
      clinical outcomes study of patients treated for chronic sinusitis at a tertiary
      care academic medical center (n = 57, mean age 46.8 years). Disease-specific
      symptom severity was measured with a validated health status instrument, and CT
      stage was quantified with the Harvard CT staging system. RESULTS: In a
      multivariate analysis, symptom severity based on CT findings emerged as a strong
      predictor of both improvement in symptom score outcome (beta = 0.47, P = 0.01)
      and absolute symptom level after treatment (beta = -0.58, P = 0.001).
      CONCLUSIONS: Severity as assessed by a pretreatment CT scan is a strong predictor
      of outcome. Patients with higher symptom severity based on CT scans showed
      significantly larger improvement and lower absolute levels of symptom severity
      after treatment. This study links CT scan findings and subjective patient-based
      outcomes (symptom scores) using a validated outcomes instrument.

PMID- 10889487
TI  - Growth-related oncogene-alpha expression in human nasal polyps.
AB  - The cytokine growth-related oncogene-alpha (GRO-alpha) is a potent mediator of
      leukocyte recruitment and proliferation in inflammatory diseases. We hypothesized
      that GRO-alpha is produced in the inflammatory nasal polyp microenvironment.
      Evaluation of nasal polyps from 27 patients for distribution and content of GRO
      alpha antigen, by use of immunohistochemical techniques and ELISA, revealed its
      presence in all 27 tissue samples. It was found predominantly within the
      eosinophils and neutrophils, with tissue levels ranging from 34 pg/mg total
      protein (TP) to 1746 pg/mg TP, with a mean value of 631 +/-98 pg/mg TP. Control
      tissues contained between 82 pg/mg TP and 316 pg/mg TP (mean 176+/-38 pg/mg TP).
      These results were statistically significant (P<0.03). Clinical correlations and
      statistical comparisons were calculated. These data suggest that GRO-alpha may be
      an important factor in the recruitment and activation of leukocytes in nasal
      polyposis, making it a potential target for therapeutic intervention.

PMID- 10889488
TI  - Round window membrane permeability to transforming growth factor-alpha: an in
      vitro study.
AB  - OBJECTIVE: Recent studies have identified the capacity of transforming growth
      factor-alpha (TGF-alpha) to stimulate mammalian labyrinthine hair cell
      regeneration after acute ototoxic damage. Augmenting hair cell regeneration with
      such growth factors may have a role in potentiation of recovery of cochlear
      function after hair cell injury. Transtympanic application of aqueous solutions
      to the round window membrane (RWM) has proved successful as a drug delivery
      route. The purpose of this study was to test the permeability of the mammalian
      RWM to TGF-alpha in an inexpensive and reliable in vitro model. METHODS: Guinea
      pig RWM niches were harvested and transferred to a 2-chamber apparatus, and TGF
      alpha was applied to the middle-ear side of the chamber. ELISAs of TGF-alpha were
      measured at intervals during a 96-hour period. RESULTS: Aliquots taken during a
      96-hour interval demonstrated passage of TGF-alpha in concentrations sufficient
      to stimulate hair cell regrowth. CONCLUSIONS: The apparatus allows study of RWM
      permeability to other substances and provides a basic model for study of RWM
      physiology. TGF-alpha is able to pass through a mammalian RWM.

PMID- 10889489
TI  - Measurement of peripheral vestibular blood flow in a gerbil model of
      endolymphatic hydrops.
AB  - Presently, many investigators believe that the dysfunction of microcirculatory
      mechanisms may be responsible for vestibular symptoms in Meniere's disease. This
      study, using intravital microscopy (IVM), a technique that provides in vivo
      microcirculatory measures, was designed to determine whether impaired vestibular
      blood flow exists in endolymphatic hydrops. Hydrops was induced in the gerbil
      model by obliteration of the vestibular aqueduct and was confirmed histologically
      after IVM. Posthydrops gerbil subjects at 8 weeks as well as control animals were
      prepared for IVM. With a customized intravital microscope, red blood cell
      velocity and vessel diameter measurements were calculated for individual
      arterioles and capillaries from the microvascular bed at the horizontal ampulla.
      Mean arteriole diameter was significantly larger in the control group than in the
      hydrops group, whereas mean capillary diameters were similar for both groups. No
      significant difference was observed for mean red blood cell velocity in
      capillaries or arterioles between control and hydrops animals.

PMID- 10889490
TI  - Use of the laryngeal mask airway for laser treatment of the subglottis.
AB  - A technique for treating subglottic lesions with the intubating laryngeal mask
      airway is described. It provides unhampered exposure of the subglottis and upper
      trachea, excellent airway control, and a means of access for ablation with
      flexible laser bronchoscopy.

PMID- 10889491
TI  - New unidirectional airflow ball tracheostomy speaking valve.

PMID- 10889492
TI  - Platinum ribbon-Teflon piston reduces device failure after stapes surgery.

PMID- 10889493
TI  - Role of the new imaging modalities in the investigation of Meniere's disease.
AB  - The incidence of nonvisualization of the vestibular aqueduct and the
      endolymphatic duct-endolymphatic sac (ED-ES) complex as well as the type of
      periaqueductal pneumatization were evaluated in 23 patients with definite
      Meniere's disease (MD) by high-resolution CT and by MRI. Fifty subjects with no
      previous history of any ear disease were used as a control group. High-resolution
      CT results disclosed that in the control group the percentage of nonvisualized
      vestibular aqueduct (3.4%) was statistically significantly lower than in the MD
      group, when either the diseased ear (27.8%) or the nondiseased ear of the same
      group (22.2%) was examined. In addition, no differences were observed between the
      diseased and nondiseased ears of the patients with MD. The periaqueductal
      pneumatization was also found to be statistically significantly lower in the MD
      group. As regards the MRI examination, the results of the analysis showed that
      the ED-ES complex was visualized more frequently in the ears of the control
      subjects (64.1%) than in the diseased ears of the patients with Meniere's disease
      (39.1%). This difference had a marginal statistical significance (P approximately
      0.05). We discussed the results in relation to possible underlying
      pathophysiologic mechanisms involving the flow of endolymph toward the ES during
      the different stages of the disease.

PMID- 10889494
TI  - Active ion secretion and permeability of rabbit maxillary sinus epithelium,
      impact of staphylococcal enterotoxin B.
AB  - The aim of this study was to investigate the impact of staphylococcal enterotoxin
      B (SEB), a model superantigen, on the physiologic functions of rabbit maxillary
      sinus epithelium. Rabbit sinus mucosae were separated under a surgical microscope
      and mounted in Ussing chambers to record short-circuit current, conductance, and
      permeability to horseradish peroxidase. The results showed that SEB evoked
      increases in sinus epithelial cell baseline short-circuit current, conductance,
      and permeability to horseradish peroxidase. When tumor necrosis factor-alpha (TNF
      alpha) was added to the Ussing chambers, we got results similar to those obtained
      by SEB stimulation in vitro; the effects of SEB on sinus epithelial cells could
      be blocked by pretreatment with anti-TNF-alpha antibody. These results
      demonstrate that SEB is able to alter the function of sinus epithelial cells and
      to affect the capability of the epithelial defensive barrier, which may be
      mediated by TNF-alpha.

PMID- 10889495
TI  - Endoscopic CO2 laser excision for tis, T1, and T2 glottic carcinomas: cure rate
      and prognostic factors.
AB  - We present the results of a retrospective study based on a cohort of 140 patients
      who underwent endoscopic CO(2) laser excision for previously untreated early
      glottic cancer (21 Tis, 96 T1, and 23 T2). This study used univariate analysis to
      review the impact on disease-free survival of 15 factors related to the host, the
      tumor, and the treatment. Recurrent cancer developed in 28 patients with an
      average interval to recurrence of 37.5 months. Retreatment consisted of different
      procedures, including laser excision, partial or total laryngectomy, and/or
      radiotherapy. The larynx was definitively preserved in 96% of patients. By the
      end of the study, 14 patients had died, but only 2 of them had died of the
      disease. Five-year overall survival and determinate survival were 93% and 98%,
      respectively. Ultimate local control at 5 years with CO(2) laser excision alone
      was 95% for Tis, 87% for T1, and 91% for T2 lesions. Only involvement of the
      anterior third of the vocal cord (P = 0.02), involvement of the false vocal cord
      (P = 0.02), and infiltration of the vocalis muscle (P = 0.004) showed a
      significant negative impact on disease-free survival.

PMID- 10889496
TI  - Immunomodulating effects of surgical intervention in tumors of the head and neck.
AB  - The immunomodulating effect of primary surgical intervention in 33 patients with
      squamous cell carcinoma of the oral cavity, pharynx, and larynx was analyzed
      prospectively. An operation time of longer than 7 hours was significantly
      associated with a decrease of total lymphocyte counts, CD4(+) T lymphocytes, and
      CD8(+) T lymphocytes. The CD4/CD8 ratio as a marker for the downregulation of the
      cellular immune response was slightly decreased but still in the normal range.
      CD4(+) lymphocyte counts increased within 7 days, and CD8(+) lymphocytes
      increased 4 weeks after the operation. The in vitro stimulation of the
      lymphocytes was impaired for 1 to 4 weeks. Release of interleukins, interferon
      gamma, and tumor necrosis factor-alpha remained low despite the surgical trauma.
      The decreased lymphocyte counts, especially CD4(+) and CD8(+) lymphocytes, were
      significantly associated with duration of operation and volume of blood loss.
      Extension of trauma, age, type of anesthesia, and type of intensive care
      intervention were not associated with specific immunomodulating effects. However,
      these factors might be responsible for suppression of the immune system, which is
      expressed by lymphocyte depletion, lymphocyte dysfunction, and impaired
      upregulation of cytokine secretion.

PMID- 10889498
TI  - Pleomorphic adenoma of the trachea.

PMID- 10889497
TI  - Histologic evaluation of retrieved craniofacial implants.
AB  - A retrieval study was performed on implants placed extraorally in the
      craniofacial region. The study included 19 implants retrieved from 16 patients.
      The implants were all stable at the time of removal. For various reasons, 5 of
      the implants were never loaded, whereas 14 of the implants had a known loading
      period of 3 months to 7 years 7 months. The reasons for removal varied but
      included the following: death in 1 case; poor results of the bone-anchored
      hearing aid in 7 cases; host-related reasons, varying from soft tissue irritation
      to infection or pain, in 6 cases; change of treatment plan in 1 case; and
      scheduled direct removal at the time of insertion in 1 case. The results of the
      histologic evaluation were similar to those reported in retrieval studies of a
      corresponding design used intraorally.

PMID- 10889499
TI  - Huge congenital cholesteatoma simulating an intracranial abscess.

PMID- 10889500
TI  - Postcricoid sarcoid mimicking a malignancy: a lesson to remember.

PMID- 10889501
TI  - Kaposi's sarcoma of the tongue.

PMID- 10889502
TI  - Practical approach to digital photography and its applications.

PMID- 10889503
TI  - Two or three (thousands) things to do before dying.

PMID- 10889504
TI  - Life and death decisions: regulation of apoptosis by proteolysis of signaling
      molecules.
AB  - Caspases are the major executioners of cell death, serving as molecular
      guillotines to behead many proteins required for maintenance of cellular
      homeostasis. Identification of caspase substrates has taken on increasing
      importance as we attempt to better understand the molecular mechanisms involved
      in regulating the struggle between life and death. Many caspase substrates have
      been described and include RNA binding proteins such as La and U1-70 kD,
      structural proteins such as keratin and nuclear lamins, and transcription factors
      or their regulatory proteins that include IkappaB, SP1, and SREBP. Kinases and
      other signaling proteins are perfectly suited to regulate life and death
      decisions in response to cellular stressors and have only recently been
      identified as important caspase substrates. Here we review the current status of
      signaling pathways that are activated, inactivated or dysregulated by proteases
      such as caspases and calpain to control entry into apoptosis. The emerging
      concept that some caspase pathways may be inhibited by cellular and viral
      apoptosis inhibitory proteins while other caspase pathways are preserved suggests
      that a subset of these kinases may exist as cleaved 'isoforms' in cells that are
      not destined to perish. By acting as executioners and as important 'molecular
      sensors' of the degree of cellular injury, the signaling proteins described in
      this review are strong candidates to mediate downstream events, both in condemned
      and in viable cells.

PMID- 10889505
TI  - Translation initiation factor modifications and the regulation of protein
      synthesis in apoptotic cells.
AB  - The rate of protein synthesis is rapidly down-regulated in mammalian cells
      following the induction of apoptosis. Inhibition occurs at the level of
      polypeptide chain initiation and is accompanied by the phosphorylation of the
      alpha subunit of initiation factor eIF2 and the caspase-dependent cleavage of
      initiation factors eIF4G, eIF4B, eIF2alpha and the p35 subunit of eIF3.
      Proteolytic cleavage of these proteins yields characteristic products which may
      exert regulatory effects on the translational machinery. Inhibition of caspase
      activity protects protein synthesis from long-term inhibition in cells treated
      with some, but not all, inducers of apoptosis. This review describes the
      initiation factor modifications and the possible signalling pathways by which
      translation may be regulated during apoptosis. We discuss the significance of the
      initiation factor cleavages and other changes for protein synthesis, and the
      implications of these events for our understanding of the cellular changes
      associated with apoptosis.

PMID- 10889506
TI  - Caspase-dependent cleavage of nucleic acids.
AB  - Autoimmune diseases are frequently characterized by the presence of
      autoantibodies directed against nucleic acid-protein complexes present in the
      nucleus of the cell. The mechanisms by which these autoantigenic molecules escape
      immunological tolerance are largely unknown, although a number of recent
      observations suggest that modified self-proteins generated during apoptosis may
      play an important role in the development of autoimmunity. It has been
      hypothesized that the recognition of these modified self-proteins by the immune
      system may promote autoantibody production. While apoptosis is specifically
      characterized by posttranslational modification of proteins, recent findings also
      show that nucleic acids are modified. This review summarizes the specific
      cleavages of some of these key nucleic acids, i.e. chromosomal DNA, ribosomal RNA
      and small structural RNAs (U1 snRNA, Y RNA), in apoptotic cells.

PMID- 10889507
TI  - Cleavage of polypeptide chain initiation factor eIF4GI during apoptosis in
      lymphoma cells: characterisation of an internal fragment generated by caspase-3
      mediated cleavage.
AB  - Polypeptide chain initiation factor eIF4GI undergoes caspase-mediated degradation
      during apoptosis to give characteristic fragments. The most prominent of these
      has an estimated mass of approximately 76 kDa (Middle-Fragment of Apoptotic
      cleavage of eIF4G; M-FAG). Subcellular fractionation of the BJAB lymphoma cell
      line after induction of apoptosis indicates that M-FAG occurs in both ribosome
      bound and soluble forms. Affinity chromatography on m7GTP-Sepharose shows that M
      FAG retains the ability of eIF4GI to associate with both the mRNA cap-binding
      protein eIF4E and initiation factor eIF4A and that the ribosome-bound form of M
      FAG is also present as a complex with eIF4E and eIF4A. These data suggest that
      the binding sites for eIF4E, eIF4A and eIF3 on eIF4GI are retained in the caspase
      generated fragment. M-FAG is also a substrate for cleavage by the Foot-and-Mouth
      Disease Virus-encoded L protease. These properties, together with the pattern of
      recognition by a panel of antibodies, define the origin of the apoptotic cleavage
      fragment. N-terminal sequencing of the products of caspase-3-mediated eIF4GI
      cleavage has identified the major cleavage sites. The pattern of eIF4GI
      degradation and the possible roles of the individual cleavage products in cells
      undergoing apoptosis are discussed.

PMID- 10889508
TI  - Expression of TRAIL receptors in human autoreactive and foreign antigen-specific
      T cells.
AB  - Deletion of T cells due to apoptosis induction is a regulatory mechanism in the
      human immune system that may be impaired in autoimmune diseases such as multiple
      sclerosis (MS). Involvement of the apoptosis-mediating CD95/CD95 ligand system in
      MS has been demonstrated. Here, we report that (auto)antigen-specific human T
      cells are not killed in vitro by soluble TNF-related apoptosis-inducing ligand
      (TRAIL) although expressing death-inducing receptors, TRAIL receptor 1 (TRAIL-R1)
      and TRAIL-R2. Apoptosis was assessed by caspase activation and DNA fragmentation,
      receptor expression was detected by RT - PCR and flow cytometry. The
      (auto)antigen-specific T cells were also resistant to specific TRAIL-R1/TRAIL-R2
      directed induction of apoptosis, indicating that coexpression of the truncated
      TRAIL-R3 and TRAIL-R4 in these T cells is not responsible for the observed
      resistance. Upon stimulation, levels of death-inducing TRAIL receptors decreased
      whereas TRAIL was up-regulated on the cell surface. In contrast to CD95, the role
      of TRAIL receptors in MS might not involve regulation of T cell vulnerability.

PMID- 10889509
TI  - Surface expression of phosphatidylserine on macrophages is required for
      phagocytosis of apoptotic thymocytes.
AB  - Cells generally maintain an asymmetric distribution of phospholipids across the
      plasma membrane bilayer, restricting the phospholipid, phosphatidylserine (PS),
      to the inner leaflet of the plasma membrane. When cells undergo apoptosis, this
      asymmetric transbilayer distribution is lost, bringing PS to the surface where it
      acts as a signal for engulfment by phagocytes. The fluorescent dye merocyanine
      540 specifically stains the plasma membrane of apoptotic cells which have lost
      their asymmetric distribution of phospholipids. However, it also stains non
      apoptotic macrophages, suggesting that phospholipid asymmetry may not be
      maintained in these cells, and thus that they may express PS on their surface.
      Here, the PS-binding protein, annexin V, was used to show that in fact normal
      macrophages do express PS on their surface. Furthermore, pre-treating macrophages
      with annexin V was found to inhibit phagocytosis of apoptotic thymocytes and
      thymocytes on which PS expression was artificially induced, but did not inhibit
      phagocytosis of latex beads or Fc receptor-mediated phagocytosis of opsonized
      erythrocytes. These results indicate that PS is constitutively expressed on the
      surface of macrophages and is functionally significant for the phagocytosis of PS
      expressing target cells.

PMID- 10889510
TI  - IGF-I receptor activation and BCL-2 overexpression prevent early apoptotic events
      in human neuroblastoma.
AB  - The type I insulin-like growth factor receptor (IGF-IR) is important for
      mitogenesis, transformation, and survival of tumor cells. The current study
      examines the effect of IGF-IR expression and activation on apoptosis in SHEP
      human neuroblastoma cells. SHEP cells undergo apoptosis which is prevented by IGF
      I addition or overexpression of the IGF-IR (SHEP/IGF-IR cells). High mannitol
      treatment activates caspase-3 by 1 h in SHEP cells while caspase-3 activation is
      delayed by 3 h in SHEP/IGF-IR cells. Transfection with Bcl-2 (SHEP/Bcl-2 cells)
      prevents serum withdrawal and mannitol induced apoptosis and caspase-3
      activation. Mannitol induces mitochondrial membrane depolarization in both SHEP
      and SHEP/IGF-IR cells. IGF-IR activation or overexpression of Bcl-2 in SHEP cells
      prevents mitochondrial membrane depolarization. Collectively, these results
      suggest that IGF-IR or Bcl-2 overexpression in neuroblastoma cells promotes cell
      survival by preventing mitochondrial membrane depolarization and caspase-3
      activation, ultimately leading to increased tumor growth.

PMID- 10889511
TI  - Selective localization of Bcl-2 to the inner mitochondrial and smooth endoplasmic
      reticulum membranes in mammalian cells.
AB  - Bcl-2, an anti-apoptotic protein, is believed to be localized in the outer
      mitochondrial membrane, endoplasmic reticulum, and nuclear envelope. However, Bcl
      2 has also been suggested as playing a role in the maintenance of mitochondrial
      membrane potential, indicating its possible association with the inner
      mitochondrial membrane. We therefore further examined the exact localization of
      Bcl-2 in mitochondria purified from wild-type and bcl-2-transfected PC12 cells
      and pre- and postnatal rat brains. Double immunostaining demonstrated that Bcl-2
      was co-localized with subunit beta of F1F0ATPase in the inner mitochondrial
      membrane. Biochemical analysis of isolated mitochondria using digitonin and
      trypsin suggests an association of Bcl-2 with the inner mitochondrial membrane.
      More interestingly, the majority of Bcl-2 disappeared from the inner membrane of
      mitochondria when cultured under serum deprivation. These results suggest that
      Bcl-2 acts as an anti-apoptotic regulator by localizing mainly to the inner
      mitochondrial and smooth ER membranes.

PMID- 10889512
TI  - p53 accumulation due to down-regulation of ubiquitin: relevance for neuronal
      apoptosis.
AB  - The p53 tumor suppressor protein is a major regulator of cell growth arrest and
      apoptosis in response to DNA damage. Both p53 function and stability are tightly
      controlled by Mdm2, which binds to the p53 N-terminus and targets p53 for
      ubiquitin-mediated proteolysis. Previous studies suggest that adrenalectomy
      induced neuronal apoptosis is p53-dependent. Here we demonstrate both nuclear
      accumulation and functional activation of p53 protein in apoptotic hippocampal
      neurons from adrenalectomized rats. Increased p53 expression occurred despite the
      accumulation of its negative regulator, Mdm2, and the formation of p53-Mdm2
      complexes. The persistence of p53 expression was explained by a striking decrease
      in free ubiquitin in p53-positive neurons. The addition of exogenous ubiquitin to
      p53-Mdm2 complexes from apoptotic neurons restored p53 degradation. These
      findings demonstrate a novel mechanism of p53 stabilization mediated by decreased
      ubiquitin levels. Regulation of free ubiquitin may therefore be an effective way
      to modulate p53-dependent apoptosis in certain cell types.

PMID- 10889513
TI  - Toxic oil syndrome (TOS). Foreword.

PMID- 10889514
TI  - Short-term adverse effects in humans of ingested mineral oils, their additives
      and possible contaminants--a review.
AB  - The toxicological databases for petroleum refinery products such as mineral oils,
      as well as for their potential contaminants and additives, were reviewed for
      human cases of poisoning by the oral route. The aim was to determine whether any
      overlooked adulterant in the oil implicated as the cause of the 1981 outbreak of
      Toxic Oil Syndrome (TOS) in Spain, may have been responsible for the unusual
      symptomatology characterizing this disease. The essential features of TOS were
      peripheral eosinophilia, pulmonary oedema and endothelial damage in the acute
      phase; myalgia, sensory neuropathy, hepatic injury, skin oedema and sicca in the
      intermediate phase; and peripheral neuropathy, muscle wasting, scleroderma and
      hepatopathy in the chronic phase. Of the more than 70 chemical entities and
      mixtures reviewed here, none had been reported as producing adverse toxic effects
      upon ingestion resembling the specific set of symptoms and progression that
      characterized TOS. Because of their viscosity, the most commonly recorded disease
      process associated with oral ingestion of petroleum refinery products was lipid
      pneumonia, implicating lung exposure via aspiration. The mineral oil additives
      and contaminants comprised a highly diverse range of chemical entities, producing
      a variety of symptoms in instances of poisoning. Specifically, no chemical entity
      amongst the refinery products, additives or contaminants was described as
      inducing a syndrome involving vasculitis accompanied by thrombotic events, along
      with immunological consequences (such as T-lymphocyte activation and cytokine
      release), as is considered to be the cellular basis of TOS.

PMID- 10889515
TI  - Cholinesterase activities determination in frozen blood samples: an improvement
      to the occupational monitoring in developing countries.
AB  - 1. Studies were carried out on rural workers in Brazil to determine the decrease
      in the activity of plasma butyrylcholinesterase (BChE), erythrocyte
      cholinesterase (AChE) associated with exposure to organophosphorus pesticides
      (OP). The goal of this work is to help prevent injury to these workers. 2. In
      developing countries the distance between area of pesticide use and reference
      laboratories is a drawback for analytical techniques, since cholinesterase
      activity determinations require fresh blood samples. Field methodologies can be a
      useful alternative to laboratory tests, however they are not as sensitive as
      those found in laboratories. 3. The modification of Ellman's Method presented in
      this paper allows blood samples to be frozen and maintain enzymatic stability: 7
      days for AChE and 3 days for BChE. The proposed method is also more sensitive
      than Ellman's Method Modified by Magnotti (EMMM). 4. The results suggest that the
      Ellman Method Modified by Oliveira-Silva (EMMOS) is valid for monitoring
      procedures. This method represents an important contribution to the process of
      monitoring OP exposures, since the evaluations no longer have to be conducted
      near the site of OP use.

PMID- 10889516
TI  - In vitro metabolism and interaction of cilostazol with human hepatic cytochrome
      P450 isoforms.
AB  - 1. Cilostazol (OPC-13013) undergoes extensive hepatic metabolism. The
      hydroxylation of the quinone moiety of cilostazol to OPC-13326 was the
      predominant route in all the liver preparations studies. The hydroxylation of the
      hexane moiety to OPC-13217 was the second most predominant route in vitro. 2.
      Ketoconazole (1 microM) was the most potent inhibitor of both quinone and hexane
      hydroxylation. Both the CYP2D6 inhibitor quinidine (0.1 microM) and the CYP2C19
      inhibitor omeprazole (10 microM) failed to consistently inhibit metabolism of
      cilostazol via either of these two predominant routes. 3. Data obtained from a
      bank of pre-characterized human liver microsomes demonstrated a stronger
      correlation (r2=0.68, P < 0.01) between metabolism of cilostazol to OPC-13326 and
      metabolism of felodipine, a CYP3A probe, that with probes for any other isoform.
      Cimetidine demonstrated concentration-dependent competitive inhibition of the
      metabolism of cilostazol by both routes. 4. Kinetic data demonstrated a Km value
      of 101 microM for cilostazol, suggesting a relatively low affinity of cilostazol
      for CYP3A. While recombinant CYP1A2, CYP2D6 and CYP2C19 were also able to
      catalyze formation of specific cilostazol metabolites, they did not appear to
      contribute significantly to cilostazol metabolism in whole human liver
      microsomes.

PMID- 10889517
TI  - Comparison of the acute hematotoxicity of 2-butoxyethanol in male and female F344
      rats.
AB  - Administration of 2-butoxyethanol (BE) to rodents causes acute hemolytic anemia,
      and metabolic activation of BE to butoxyacetic acid (BAA) is required for the
      development of this effect. Recent studies have shown that female rats treated
      with BE exhibit a variety of histopathologic lesions that are absent in males and
      many of these lesions are attributed to the hemolytic effects of BE. Current
      studies were designed to compare the acute hematotoxicity of BE in male and
      female F344 rats. Rats were treated with 250 mg BE/kg body weight or water
      (control; 5 ml/kg) by gavage. At 4, 8, or 24 h after dosing, rats were
      anesthetized, blood was collected by cardiac puncture, and various blood
      parameters were measured. BE resulted in a time-dependent swelling of
      erythrocytes as evidenced by an early increase in hematocrit (Hct) and mean cell
      volume (MCV) in male rats. In contrast, increased Hct in female rats did not
      accompany an increase in MCV. It is likely that hemolysis was so severe at 4 h
      that Hct exhibited a decline in female rats at that time point. Subsequently, red
      blood cell (RBCs), hemoglobin concentration (Hgb), and Hct declined as hemolysis
      progressed. However, the onset of BE-induced hemolysis was faster in female
      compared to male rats. These effects were also associated with a significant
      increase in the spleen weight to body weight ratio. Blood smears were also
      prepared and morphological changes evaluated by light microscopy included
      stomatocytosis, spherocytosis, and schistocytosis. Furthermore, aggregation of
      RBCs in female rats as evidenced by increased formation of rouleaux was observed
      at 24 h after BE administration. These effects were observed earlier and more
      frequently in female rats. No differences in the sensitivity of RBCs obtained
      from male and female rats and exposed to butoxyacetic acid (BAA) in vitro was
      observed as determined by measuring the packed cell volume. In conclusion, these
      data suggest that female rats are more sensitive to hemolysis and morphological
      alterations of erythrocytes induced by BE during the first 24 h after exposure
      compared to males. It is likely that the greater sensitivity of female rats to BE
      effects on RBCs may account for the reported development of thrombosis and tissue
      infarction in female rats.

PMID- 10889519
TI  - Dopamine D3 receptor gene expression in the shell of nucleus accumbens is
      increased by chronic antidepressant treatment.

PMID- 10889518
TI  - Peroxisome proliferators induce apoptosis and decrease DNA synthesis in hepatoma
      cell lines.
AB  - We examined the effects of various peroxisome proliferators (PPs) such as the
      hypolipidaemic agents clofibric acid (CLO), bezafibrate (BEZA), ciprofibrate
      (CIPRO) and nafenopin (NAFE) and the plasticizer di-(2-ethylhexyl)phthalate
      (DEHP) on peroxisomal enzyme activities, apoptosis and DNA synthesis in rat FaO
      and human HepG2 hepatoma cell lines. Both growing and confluent cultures were
      treated with PPs (250 microM) for 48 or 72 h. In accordance with our previous
      observations in PP-treated primary hepatocyte cultures of rat and human origin,
      the various PPs increased peroxisomal enzyme activities in rat FaO cells but not
      in human HepG2 cells. PPs strongly induced apoptosis in FaO cells. They did not
      affect TGFbeta-induced apoptosis, with the exception of DEHP and NAFE,
      respectively blocking and increasing induced apoptosis in confluent cultures.
      Moreover, PPs produced a minor, but significant, decrease in DNA synthesis in FaO
      cells. PPs also decreased DNA synthesis in growing HepG2 cells, and CLO, CIPRO
      and NAFE induced apoptosis in confluent HepG2 cultures. This is in opposition
      with the effects of PPs on primary hepatocyte cultures, i.e. inhibition of both
      spontaneous and TGFbeta-induced apoptosis and increases in DNA synthesis in rat
      hepatocytes, and unchanged mitosis-apoptosis balance in human hepatocytes.

PMID- 10889520
TI  - Astrocyte failure as a cause of CNS dysfunction.

PMID- 10889521
TI  - Serotonin transporter linked polymorphic region in anorexia nervosa and bulimia
      nervosa.

PMID- 10889522
TI  - Polyglutamine-containing proteins in schizophrenia: an effect of lymphoblastoid
      cells?

PMID- 10889523
TI  - Polyglutamine tracts in schizophrenia: gaining new insights.

PMID- 10889524
TI  - Lack of association between schizophrenia and a CAG repeat polymorphism of the
      hSKCa3 gene in a north eastern US sample.

PMID- 10889525
TI  - The CCK-A receptor gene possibly associated with positive symptoms of
      schizophrenia.

PMID- 10889526
TI  - Interaction of two genes possibly involved in the regulation of the amyloid
      precursor protein (APP) processing.

PMID- 10889527
TI  - Dysthymia: a review of pharmacological and behavioral factors.
AB  - Although dysthymia, a chronic, low-grade form of depression, has a morbidity rate
      as high as that of major depression, and increases the risk for major depressive
      disorder, limited information is available concerning the etiology of this
      illness. In the present report we review literature concerning the biological and
      characterological features of dysthymia, the effectiveness of antidepressant
      treatments, the influence of stressors in the precipitation and maintenance of
      the disorder, and both quality of life and psychosocial correlates of the
      illness. We also provisionally suggest that dysthymia may stem from disturbances
      of neuroendocrine and neurotransmitter functioning (eg, corticotropin releasing
      hormone and arginine vasopressin within the hypothalamus, or alternatively
      monoamine variations within several extrahypothalamic sites), and may also
      involve cytokine activation. The central disturbances may reflect phenotypic
      variations of neuroendocrine processes or sensitization of such mechanisms. It is
      suggested that chronic stressor experiences or stressors encountered early in
      life lead to the phenotypic neurochemical alterations, which then favor the
      development of the dysthymic state. Owing to the persistence of the neurochemical
      disturbances, vulnerability to double depression is increased, and in this
      instance treatment with antidepressants may attenuate the symptoms of major
      depression but not those of the basal dysthymic state. Moreover, the residual
      features of depression following treatment may be indicative of underlying
      neurochemical disturbances, and may also serve to increase the probability of
      illness recurrence or relapse.

PMID- 10889528
TI  - Adult brain neurogenesis and psychiatry: a novel theory of depression.
AB  - Neurogenesis (the birth of new neurons) continues postnatally and into adulthood
      in the brains of many animal species, including humans. This is particularly
      prominent in the dentate gyrus of the hippocampal formation. One of the factors
      that potently suppresses adult neurogenesis is stress, probably due to increased
      glucocorticoid release. Complementing this, we have recently found that
      increasing brain levels of serotonin enhance the basal rate of dentate gyrus
      neurogenesis. These and other data have led us to propose the following theory
      regarding clinical depression. Stress-induced decreases in dentate gyrus
      neurogenesis are an important causal factor in precipitating episodes of
      depression. Reciprocally, therapeutic interventions for depression that increase
      serotonergic neurotransmission act at least in part by augmenting dentate gyrus
      neurogenesis and thereby promoting recovery from depression. Thus, we hypothesize
      that the waning and waxing of neurogenesis in the hippocampal formation are
      important causal factors, respectively, in the precipitation of, and recovery
      from, episodes of clinical depression.

PMID- 10889529
TI  - Dopamine receptor D2 Ser/Cys 311 variant is associated with delusion and
      disorganization symptomatology in major psychoses.
AB  - The D2 receptor (DRD2) is a binding site of many psychoactive drugs and it has
      been proposed as a genetic risk factor for psychiatric disorders. The aim of this
      investigation was to study the DRD2 S311C variant in major psychoses. We studied
      1182 inpatients with diagnoses of bipolar disorder (n = 480), major depressive
      disorder (n = 269), schizophrenia (n = 366), delusional disorder (n = 44),
      psychotic disorder not otherwise specified (n = 23) and 267 healthy controls.
      Eight hundred and eighty-seven subjects were also scored for their lifetime
      symptomatology using the the Operational Criteria checklist for psychotic illness
      (OPCRIT). DRD2 variants were not associated with affected subjects even when
      possible confounders like gender and onset were considered. When we considered
      the 887 subjects with the symptomatologic analysis, we observed a significant
      association of the DRD2 S311C variant with both delusion and disorganization
      features. The association was present independently from diagnoses. Our results
      do not show that coding variants of the DRD2 S311C play a major role in
      conferring susceptibility to major psychoses, but they may be connected with
      disorganized and delusional symptomatology independently from diagnoses.

PMID- 10889530
TI  - Systematic screening for DNA sequence variation in the coding region of the human
      dopamine transporter gene (DAT1).
AB  - The dopamine transporter (DAT) plays a central role in dopaminergic
      neurotransmission in the human brain. Genetic association studies have used a
      variable number of tandem repeat (VNTR) polymorphism in the 3'-flanking region of
      the dopamine transporter gene (DAT1) to implicate the DAT in the development of
      various neuropsychiatric disorders. In this study, we have examined the
      possibility that a mutation exists in the coding region of the DAT1 gene which
      through linkage disequilibrium accounts for the observed associations. The
      complete coding region, as well as exon-intron boundaries, was screened in 91
      unrelated individuals including 45 patients with bipolar affective disorder and
      46 healthy control individuals by the means of single strand conformation
      analysis. Our findings suggest that the DAT1 gene is highly conserved since we
      detected only two rare missense substitutions (Ala559Val, Glu602Gly) and three
      silent mutations (242C/T, 1342A/G, and 1859C/T) in the whole coding region. Five
      sequence variants were observed in intronic sequences but none affects known
      splice sites. The lack of frequent variants of possible functional relevance
      indicates that genetic variation in the coding region of the DAT1 gene is not
      responsible for the previously observed associations with neuropsychiatric
      disorders. The two rare missense substitutions were found in single bipolar
      patients but not in controls. Investigation of the patients' families revealed
      independent segregation between the Ala559Val variant and affective disorder. The
      Glu602Gly variant was inherited by the proband from an affected father. It
      therefore remains possible that Glu602Gly may be a rare cause of bipolar
      affective disorder.

PMID- 10889531
TI  - Human dopamine transporter gene: coding region conservation among normal,
      Tourette's disorder, alcohol dependence and attention-deficit hyperactivity
      disorder populations.
AB  - The dopamine transporter (DAT) provides major regulation of the synaptic levels
      of dopamine and is a principal target of psychostimulant drugs. Associations
      between DAT gene polymorphisms and human disorders with possible links to
      dopaminergic neurotransmission, including attention-deficit/hyperactivity
      disorder (ADHD) and consequences of cocaine and alcohol administration, have been
      reported. We now report approximately 60000 bp of genomic sequence containing the
      entire DAT gene. This sequence was used to amplify each of the 15 DAT gene exons
      and several introns and analyze these amplification products by single-stranded
      sequence conformation (SSCP) and/or direct sequencing. These results define
      silent allelic single nucleotide sequence variants in DAT gene exons 2, 6, 9 and
      15. Rare conservative mutations are identified in amino acids encoded by DAT
      exons 2 and 8. Analyses of the common nucleotide variants and the previously
      reported VNTR in the non-coding region of exon 15 define the pattern of linkage
      disequilibrium across the DAT locus. These comprehensive analyses, however, fail
      to identify any common protein coding DAT sequence variant in more than 150
      unrelated individuals free of neuropsychiatric disease, 109 individuals meeting
      City of Hope criteria for Tourette's syndrome, 64 individuals with DSM-IV
      diagnoses of ethanol dependence, or 15 individuals with ADHD. These data are
      consistent with substantial evolutionary conservation of the DAT protein
      sequence. They suggest that gene variants that alter levels of DAT expression
      provide the best current candidate mechanism for reported associations between
      DAT gene markers, ADHD and other more tentatively associated neuropsychiatric
      disorders.

PMID- 10889532
TI  - Abnormal expression of brain-derived neurotrophic factor and its receptor in the
      corticolimbic system of schizophrenic patients.
AB  - Previous neuropathological studies have revealed that the corticolimbic system of
      schizophrenic patients expresses abnormal levels of various synaptic molecules,
      which are known to be influenced by the neuronal differentiation factors,
      neurotrophins. Therefore, we determined levels of neurotrophins and their
      receptors in the postmortem brains of schizophrenic patients and control subjects
      in relation to molecular impairments in schizophrenia. Among the neurotrophins
      examined, levels of brain-derived neurotrophic factor (BDNF) were elevated
      specifically in the anterior cingulate cortex and hippocampus of schizophrenic
      patients, but levels of nerve growth factors and neurotrophin-3 showed no change
      in any of the regions examined. In parallel, the expressions of TrkB receptor and
      calbindin-D, which are both influenced by BDNF, were reduced significantly in the
      hippocampus or the prefrontal cortex. However, neuroleptic treatment did not
      appear to mimic the neurotrophic change. Neither withdrawal of drug treatment in
      patients nor chronic administration of haloperidol to rats altered levels of
      BDNF. These findings suggest that neurotrophic abnormality is associated with the
      corticolimbic structures of schizophrenic patients and might provide the
      molecular substrate for pathological manifestations of the illness.

PMID- 10889533
TI  - Association analysis of the GABA(A) receptor subunit genes cluster on 5q33-34 and
      alcohol dependence in a Japanese population.
AB  - Recent investigations suggest that genetic susceptibility to alcohol dependence
      may be conferred by GABA(A) receptor subunit genes. In this study, three RFLPs at
      the GABA(A)beta2, GABAAalpha6, GABA(A)alpha1 and two at the GABA(A)gamma2
      receptor subunit genes, were examined for association with alcohol dependence in
      189 subjects meeting DSM-III-R criteria for this disorder and 152 unrelated
      controls from a Japanese population. The results demonstrated no association
      between the AlwNI RFLP at the GABA(A)alpha6 receptor subunit gene and alcohol
      dependence (P = 0.059). However, the NciI RFLP at the GABA(A)gamma2 receptor
      subunit gene was associated with alcohol dependence comorbid with antisocial
      personality disorder (P = 0.021). This supports a recent finding reporting an
      association between the GABA(A)gamma2 receptor subunit gene and alcohol
      dependence with criminal record in a Finnish population. Taking into account the
      effects of multiple comparisons, this result should be interpreted with caution
      pending replication.

PMID- 10889534
TI  - mu-opioid receptor and alpha2-adrenoceptor agonist stimulation of [35S]GTPgammaS
      binding to G-proteins in postmortem brains of opioid addicts.
AB  - Repeated opioid administration has been associated in human brain with unaltered
      density of mu-opioid receptors (agonist radioligand binding sites and
      immunodetected receptor protein). These receptors are coupled to Gi/Go-proteins,
      which are increased in brain of heroin addicts. To assess the activity of G
      proteins and their coupling to receptors after chronic opioid abuse,
      [35S]GTPgammaS binding was quantified in postmortem prefrontal cortices of 15
      opioid-dependent subjects and 15 matched controls. The stimulation of
      [35S]GTPgammaS binding by the mu-opioid receptor agonist DAMGO or the alpha2
      adrenoceptor agonist UK14304 was used as a functional measure of the status of
      the receptor-G-protein coupling. [35S]GTPgammaS binding basal values were similar
      in opioid addicts (819+/-83 fmol mg-1 of protein) and controls (918+/-106 fmol
      mg(-1) of protein). In opioid addicts, [35S]GTPgammaS binding stimulation by
      DAMGO showed a maximal effect (62+/-8%) and a potency (EC50 = 1.09+/-0.26 microM)
      that did not differ from the maximal effect (60+/-12%) and potency (EC50 = 2.01+/
      0.58 microM) in controls. In opioid addicts, [35S]GTPgammaS binding stimulation
      by UK14304 was not different in maximal effect (28+/-3%) from controls (32+/-8%),
      but the potency of the agonist was decreased (EC50 = 4.36+/-1.81 microM) when
      compared with controls (EC50 = 0.41+/-0.15 microM). The results provide a direct
      evidence of an apparent normal functional activity of brain mu-opioid receptors
      (Gi/Go-protein coupling) during the opioid dependence process in humans. The data
      also demonstrate a functional uncoupling of alpha2-adrenoceptors from G-proteins,
      which indicates a heterologous desensitization of these receptors. This finding
      could represent an adaptive mechanism against the decreased noradrenergic
      activity induced by the chronic presence of opioid drugs.

PMID- 10889535
TI  - Identification of a naturally occurring Pro385-Ser385 substitution in the GABA(A)
      receptor alpha6 subunit gene in alcoholics and healthy volunteers.
AB  - In the rat, variation in alcohol and benzodiazepine sensitivity has been
      correlated with an inherited variant of the GABA(A)alpha6 receptor. Our goal was
      to identify polymorphisms in the human GABA(A)alpha6 receptor gene and determine
      whether a variant of the receptor is associated with alcoholism. The
      GABA(A)alpha6 receptor gene coding region was screened in 80 unrelated patients
      with alcoholism using single strand conformational polymorphism analysis. For
      rapid genotyping, a Polymerase Chain Reaction-Restriction Fragment Length
      Polymorphism (PCR-RFLP) assay was developed. A relatively abundant amino acid
      substitution and three synonymous DNA substitutions were detected. The synonymous
      variants, 35A>G, 665A>G, and 1031G>C had rare-allele frequencies of 0.25, 0.02,
      and 0.47, respectively. The Pro385Ser substitution is located in the second
      intracellular domain of the receptor adjacent to a putative phosphorylation site.
      Pro385Ser has rarer allele frequencies of 3.3% and 4.8% in 196 Finnish alcoholic
      patients and 189 controls, respectively (P = NS). A naturally occurring non
      conservative Pro385Ser was detected in the GABA(A)alpha6 receptor. The variant is
      not associated with alcoholism.

PMID- 10889536
TI  - Analysis of autism susceptibility gene loci on chromosomes 1p, 4p, 6q, 7q, 13q,
      15q, 16p, 17q, 19q and 22q in Finnish multiplex families.
AB  - The role of genetic factors in the etiology of the autistic spectrum of disorders
      has clearly been demonstrated. Ten chromosomal regions, on chromosomes 1p, 4p,
      6q, 7q, 13q, 15q, 16p, 17q, 19q and 22q have potentially been linked to autism.1
      8 We have analyzed these chromosomal regions in a total of 17 multiplex families
      with autism originating from the isolated Finnish population by pairwise linkage
      analysis and sib-pair analysis. Mild evidence for putative contribution was found
      only with the 1p chromosomal region in the susceptibility to autism. Our data
      suggest that additional gene loci exist for autism which will be detectable in
      and even restricted to the isolated Finnish population.

PMID- 10889537
TI  - Association between the methylenetetrahydrofolate reductase 677C-->T missense
      mutation and schizophrenia.
AB  - The schizophrenia phenotype is heterogeneous with respect to clinical
      presentation, long-term response to medication, and outcome, possibly reflecting
      genetic heterogeneity and/or the presence of modifier genes. Compared to non
      responders, schizophrenic patients who are responders to neuroleptic medications
      are characterized by a high female/male ratio, a better long-term outcome and
      more frequently disturbed dopamine neurotransmission. In this study, we compared
      two groups of schizophrenic patients selected on the basis of their long-term
      response to neuroleptics (excellent responders and non-responders) and a group of
      healthy volunteers, with regard to a missense mutation (677C-->T) in the
      methylenetetrahydrofolate reductase (MTHFR) gene. This polymorphism was chosen
      because it is functional and was previously associated with schizophrenia. The
      present study revealed a significant association between schizophrenia and allele
      T of this gene. This association was entirely due to an over-representation of
      allele T in responder patients compared to controls; nonresponder patients did
      not differ from controls. Genotype TT was more frequent in responder patients
      compared to controls, thus replicating the findings of Arinami et al. These
      results strongly suggest that the MTHFR gene is involved in the pathogenesis of
      schizophrenia characterized by a rapid and sustained therapeutic response to
      typical neuroleptics and/or a good long-term prognosis/favorable therapeutic
      outcome.

PMID- 10889538
TI  - Comparative sequencing and association studies of aromatic L-amino acid
      decarboxylase in schizophrenia and bipolar disorder.
AB  - Aromatic L-amino acid decarboxylase (AADC) is a relatively non specific enzyme
      involved in the biosynthesis of several classical neurotransmitters including
      dopamine and 5-hydroxytryptamine (5HT; serotonin). AADC does not catalyse the
      rate limiting step in either pathway, but is rate limiting in the synthesis of 2
      phenylethylamine (2PE) which is a positive modulator of dopaminergic transmission
      and a candidate natural psychotogenic compound.1 We and others have proposed that
      polymorphism in AADC resulting in altered 2PE activity might contribute to the
      pathogenesis of psychosis. In order to test this hypothesis, we have used
      denaturing high performance liquid chromatography (DHPLC)3 to screen 3943 bases
      of the AADC gene and its promoter regions for variants that might affect protein
      structure or expression in 15 unrelated people with schizophrenia, and 15
      unrelated people with bipolar disorder. Three polymorphisms were identified by
      DHPLC: a insertion/deletion polymorphism in the 5' UTR of the neuronal specific
      mRNA (g.-33-30delAGAG, bases 586-589 of GenBank M77828), a T>A variant in the non
      neuronal exon 1 (g. -67T>A, GenBank M88070), and a G>A polymorphism within intron
      8 (g. IVS8 +75G>A, GenBank M84598). Case-control analysis did not suggest that
      genetic polymorphism in the AADC gene is associated with liability for developing
      schizophrenia or bipolar disorder.

PMID- 10889539
TI  - Glucocorticoid modulation of dopamine mediated effects on hypothalamic atrial
      natriuretic factor neurons.
AB  - Dopamine (DA) plays an important role in cognition, neuroendocrine functions and
      psychosis.1,2 Whilst stress adversely affects some of these functions, its
      neurobiological basis remains unclear.3 In the rat hypothalamus, a concurrent
      activation of D5and D2 receptors by dopamine produces a biphasic effect on the
      function of atrial natriuretic factor (ANF) neurons.4 Whereas low doses (10-8 and
      10-7 M) of DA suppress the release and pro-ANF mRNA expression, high doses (10-6
      and 10-5 M) of the amine produce an opposite effect through the interaction of D5
      and D2 receptors. We report here that the augmenting effect of DA on the
      hypothalamic neurons is inhibited by a synthetic glucocorticoid, dexamethasone
      (DM), in both time-dependent and dose-related manner with an EC50 of 0.1 nM.
      Furthermore, the inhibition is blocked by 100 nM of RU38486 (P<0.01), a
      glucocorticoid receptor antagonist, but not by an equivalent dose of RU28318, a
      mineralocorticoid receptor antagonist. In contrast, DM failed to modulate low
      doses (10(-8) to 10(-7) M) of DA-induced suppression of ir-ANF release and pro
      ANF mRNA expression that was mediated primarily through D2 receptors. We conclude
      that glucocorticoids markedly alter DA-induced biphasic effects by down
      regulating D5, but not D2, receptor-mediated neurobiological events. Hence, in
      severe stress, high levels of circulating glucocorticoids may render dopamine to
      act as a potent suppressor of neurons that possess both D5 and D2 receptors. The
      possibility that this novel mechanism of stress hormone or glucocorticoids may,
      in part, undermine DA-mediated neurophysiology in critical regions of the brain,
      which links to psychosis now needs to be considered.

PMID- 10889540
TI  - Complexin I and II mRNAs in the human hippocampus.

PMID- 10889541
TI  - Psychiatric epigenetics: a new focus for the new century.

PMID- 10889542
TI  - CYP2A6 genotype and smoking.

PMID- 10889543
TI  - Analysis of the serotonin transporter polymorphism (5-HTTLPR) in Brazilian
      patients affected by dysthymia, major depression and bipolar disorder.

PMID- 10889544
TI  - Time-dependent sensitization: the odyssey of a scientific heresy from the
      laboratory to the door of the clinic.
AB  - This review provides both a biological and clinical perspective on Time-Dependent
      Sensitization (TDS), an ancient amplified memory response to threat manifest in
      the ability of both drugs and nondrug stressors to induce neuronal and behavioral
      effects which strengthen entirely as a function of the passage of time following
      even a single or acute exposure. Evidence is presented to show that TDS may be
      involved in the development of a spectrum of diseases and how drug regimens based
      on the principles of TDS could provide a novel and revolutionary means of
      treating psychiatric and other illnesses.

PMID- 10889545
TI  - Neurotransmitter transporters: fruitful targets for CNS drug discovery.
AB  - More than 20 members have been identified in the neurotransmitter transporter
      family. These include the cell surface re-uptake mechanisms for monoamine and
      amino acid neurotransmitters and vesicular transporter mechanisms involved in
      neurotransmitter storage. The norepinephrine and serotonin re-uptake transporters
      are key targets for antidepressant drugs. Clinically effective antidepressants
      include those with selectivity for either NE or serotonin uptake, and compounds
      with mixed actions. The dopamine transporter plays a key role in mediating the
      actions of cocaine and the amphetamines and in conferring selectivity on dopamine
      neurotoxins. The only clinically used compound to come so far from research on
      amino acid transporters is the antiepileptic drug tiagabine, a GABA uptake
      inhibitor.

PMID- 10889546
TI  - Apolipoprotein E is a genetic risk factor for fetal iodine deficiency disorder in
      China.
AB  - Fetal iodine deficiency disorder (FIDD) is the principal form of endemic
      cretinism, and the most common cause of preventable mental deficiency in the
      world. However not everyone at risk develops FIDD and familial aggregation is
      common. This suggests that genetic factors may also be involved. The
      Apolipoprotein E (APOE) gene encodes for a lipoprotein that possesses a thyroid
      hormone binding domain, and APOE genotype may affect the efficiency with which
      thyroid hormone influences neuronal cell growth during the first and second
      trimesters of fetal development. We have compared ApoE genotypes in 91 FIDD cases
      with 154 local control subjects, recruited from three iodine deficiency areas in
      central China. We have also genotyped 42 FIDD family cases and 158 normal
      individuals from the families of local controls, and 375 population controls from
      Shanghai. APOE epsilon4 genotypes were significantly enriched in FIDD probands
      from each of the three iodine deficiency areas; the epsilon4 allele frequency was
      16% vs 6% in controls. The same effect was also observed when we compared FIDD
      family cases with controls and control families. Our data suggest that in iodine
      deficient areas, the APOE epsilon4 allele is a genetic risk factor for FIDD. The
      phenomenon may affect population selection and contribute to the low frequency of
      the epsilon4 allele in Chinese compared to Caucasian populations.

PMID- 10889547
TI  - A genetic screen for novel behavioral mutations in mice.
AB  - A genetic screen using mice was performed to identify dominant loci affecting
      behavior. Mice were mutagenized with ENU, then bred to examine their G1 offspring
      for behavioral abnormalities. Potentially mutant G1 pups were screened through a
      variety of behavioral assays, including tests of learning and memory,
      sensorimotor gating, fear and anxiety, nociception (pain perception) and
      locomotor activity. Mice falling outside the normal performance distribution in
      these tests were considered potential behavioral mutants and were bred for
      further analysis. Outliers included both animals with very discrete defects and
      animals with abnormal performance across a range of tests. To date, we have
      identified two confirmed mutants affecting sensorimotor gating. These results
      provide further impetus for the use of random mutagenesis screens as a tool for
      dissecting the genetic basis of brain and behavior.

PMID- 10889548
TI  - Selective increase of dopamine D3 receptor gene expression as a common effect of
      chronic antidepressant treatments.
AB  - The mesolimbic dopaminergic system is a neuroanatomical key structure for reward
      and motivation upon which previous studies indicated that antidepressant drugs
      exert a stimulatory influence, via still unknown neurobiological mechanisms. Here
      we examined the effects of chronic administration of antidepressants of several
      classes (amitriptyline, desipramine, imipramine, fluoxetine and tranylcypromine)
      and repeated electroconvulsive shock treatments (ECT) on dopamine D3 receptor
      expression in the shell of the nucleus accumbens, a major projection area of the
      mesolimbic dopaminergic system. Short-term drug treatments had variable effects
      on D3 receptor mRNA expression. In contrast, treatments for 21 days (with all
      drugs except fluoxetine) significantly increased D3 receptor mRNA expression in
      the shell of nucleus accumbens; D3 receptor binding was also significantly
      increased by amitriptyline or fluoxetine after a 42-day treatment. ECT for 10
      days increased D3 receptor mRNA and binding in the shell of nucleus accumbens. D1
      receptor and D2 receptor mRNAs were increased by imipramine and amitriptyline,
      but not by the other treatments. The time-course of altered D3 receptor
      expression, in line with the delayed clinical efficiency of antidepressant
      treatment, and the fact that various antidepressant drugs and ECT treatments
      eventually produced the same effects, suggest that increased expression of the D3
      receptor in the shell of nucleus accumbens is a common neurobiological mechanism
      of antidepressant treatments, resulting in enhanced responsiveness to the
      mesolimbic dopaminergic system.

PMID- 10889549
TI  - Identification of candidate genes for psychiatric disorders on 18p11.
AB  - Linkage studies have suggested a locus for bipolar disorder as well as
      schizophrenia in the pericentric region of chromosome 18. Several candidate genes
      have been identified in the region including ACTH, IMP, and G(olf), however no
      reports of mutations in families showing linkage to the 18p11 locus have been
      reported. Recently, mild linkage disequilibrium has been observed with a
      polymorphic marker that maps within the G(olf) gene and schizophrenia in families
      from Germany and Israel, suggesting that a gene mapping near G(olf) may be
      involved in psychiatric disorders. A BAC and cosmid contig around the G(olf)
      locus has been generated and BAC clones were used for cDNA selection experiments.
      Several novel genes have been identified which are expressed in the brain. These
      genes may be possible candidate genes for psychiatric illness.

PMID- 10889550
TI  - Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity
      disorder (ADHD) in a sample of Turkish children.
AB  - The search for genetic factors predisposing to Attention Deficit Hyperactivity
      Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as
      dopamine receptors and enzymes that regulate levels of dopamine in the synapse.
      There have been several reports of association between ADHD and polymorphic
      variants within or near DRD4, DRD5, DAT1, DBH and COMT. In this study we set out
      to investigate specific alleles of DRD4 and DRD5, previously reported to be
      associated with ADHD, in a sample of Turkish children with DSM-IV ADHD children,
      as well as their relation to methylphenidate response and dimensional measures of
      symptom domains. One hundred and four independent trios and seven dyads were
      analysed using the transmission disequilibrium test (TDT). We found increased
      transmission of the DRD4 7-repeat allele (DRD4*7) (TDT chi2 = 2.79, P = 0.047).
      Given that we were testing specific a priori hypotheses regarding the associated
      alleles, we have used one-tailed P-values throughout. There was evidence of an
      interaction with methlyphenidate (MPH) response and analysis of the sample
      excluding non-responders revealed more significant evidence for the association
      (TDT chi2 = 4.48, P = 0.017). We also detected a trend for linkage and
      association in the DRD5 polymorphism (TDT chi2 = 2. 38, P = 0.06). Similar
      findings were obtained in relation to MPH response as analysis of MPH responders
      alone gave rise to a more significant association than that of the group as a
      whole (TDT chi2 = 4.9, P = 0.013). t-Test and logistic regression TDT analyses of
      DRD4*7 transmission with respect to dimensional rating scales of hyperactivity
      and impulsivity showed an inverse relation suggesting that in this sample DRD4*7
      is associated with a lower level of ADHD symptomatology. While this may be due to
      stratification along a dimension of severity such that severe cases belong to a
      more extreme group with other specific genetic and environmental causes, similar
      to the model for low cognitive ability, it is more likely the result of a chance
      selection bias in this sample.

PMID- 10889551
TI  - Identification of DNA variants in the SNAP-25 gene and linkage study of these
      polymorphisms and attention-deficit hyperactivity disorder.
AB  - The gene for the synaptic vesicle docking fusion protein, synaptosomal-associated
      protein of 25 kDa (SNAP-25), has been implicated in the etiology of attention
      deficit hyperactivity disorder (ADHD) based on the mouse mutant strain coloboma.
      This neutron-irradiation induced mouse strain is hemizygous for the deletion of
      the SNAP-25 gene and displays spontaneous hyperactivity that is responsive to
      dextroamphetamine. Because of these characteristics, this strain has been
      suggested to be a mouse model for ADHD. We identified using single stranded
      conformational polymorphism analysis (SSCP) four DNA sequence variants in the 3'
      untranslated region of the human SNAP-25 gene. We searched for polymorphisms in
      the 3' untranslated region because the intron/exon structure of this gene has not
      yet been determined. We tested for linkage of this gene and ADHD using two of the
      identified polymorphisms that change a restriction enzyme recognition site. We
      examined the transmission of the alleles of each of these polymorphisms and the
      haplotypes of both polymorphisms using the transmission disequilibrium test in a
      sample of 97 small nuclear families consisting of a proband with ADHD, their
      parents, and affected siblings. We observed biased transmission of the haplotypes
      of the alleles of these two polymorphisms. Our findings are suggestive of a role
      of this gene in ADHD.

PMID- 10889552
TI  - A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association
      with tardive dyskinesia in schizophrenia.
AB  - Tardive dyskinesia (TD) is a common and potentially irreversible side effect
      associated with long-term treatment with typical antipsychotics. Approximately,
      80% or more of patients with schizophrenia are smokers. Smoking is a potent
      inducer of the CYP1A2 enzyme, and is known to cause a significant decrease in
      plasma concentrations of some antipsychotics. Therefore, person-to-person
      differences in the extent of CYP1A2 induction by smoking may contribute to risk
      for the development of TD. Recently, a (C-->A) genetic polymorphism in the first
      intron of the CYP1A2 gene was found to be associated with variation in CYP1A2
      inducibility in healthy volunteer smokers. The aim of this study was to test the
      clinical importance of the (C-->A) polymorphism in CYP1A2 in relation to TD
      severity. A total of 85 patients with schizophrenia were assessed for TD severity
      using the Abnormal Involuntary Movement Scale (AIMS), and were subsequently
      genotyped for the (C-->A) polymorphism in CYP1A2. The mean AIMS score in patients
      with the (C/C) genotype (associated with reduced CYP1A2 inducibility) was 2.7-
      and 3.4-fold greater than in those with the (A/C) or (A/A) genotype, respectively
      (F[2,82] = 7.4, P = 0.0007). Further, a subanalysis in the 44 known smokers in
      our sample, revealed a more pronounced effect. The means AIMS score in smokers
      was 5.4- and 4. 7-fold greater in (C/C) homozygotes when compared to
      heterozygotes and (A/A) homozygotes, respectively (F[2,41] = 3.7, P = 0.008).
      These data suggest that the (C-->A) genetic polymorphism in the CYP1A2 gene may
      serve as a genetic risk factor for the development of TD in patients with
      schizophrenia. Further studies in independent samples are warranted to evaluate
      the applicability of our findings to the general patient population receiving
      antipsychotic medications.

PMID- 10889553
TI  - Dopamine D4 receptor 48-bp repeat polymorphism: no association with response to
      antipsychotic treatment, but association with catatonic schizophrenia.
AB  - The dopamine D4 receptor (DRD4) may play a role in the pathogenesis of
      neuropsychiatric disease and in the action of dopaminergic drugs. The 48-bp
      repeat polymorphism (48-bp VNTR) coding for a 16-amino acid segment in the third
      cytoplasmatic loop of the DRD4 was studied as a predictor of the therapeutic
      response to antipsychotics and as susceptibility factor for schizophrenia. We
      included 638 in-patients with acute schizophrenic, schizoaffective (mainly
      schizophrenic), and other nonaffective psychoses, as well as two reference
      groups: one with 278 in-patients with non-psychiatric diseases, and one with 474
      healthy volunteers. Catatonic patients (DSM-IV 295.2) more frequently carried the
      DRD4 D4.2 and D4.3 allele than did all other schizophrenic cases (P < 0.001; OR:
      2.7; CI: 1.5-4.9) and controls (P < 0.004; OR: 2.3; CI: 1.3-4.2). We found no
      significant difference in the DRD4 allele or in genotype frequencies in our
      comparison of all schizophrenic patients and controls. The subgroups with
      affected family members, and the subgroups with early or late onset of disease,
      also did not differ from the controls in DRD4 allele frequencies. The 48-bp VNTR
      was not a predictor for therapeutic outcome measured by the positive and negative
      symptoms scale. A total of 1390 subjects showed between 1 and 10 repeats (D4. 1
      and D4.10), with 25 different genotypes. These data exclude a major role of DRD4
      48-bp VNTR in response to antipsychotic therapy and as susceptibility factor for
      schizophrenia, but catatonic schizophrenia may be associated with the D4.2 and
      D4.3 alleles.

PMID- 10889554
TI  - Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major
      depression: a study of complexin mRNAs.
AB  - Complexin (cx) I and cx II are synaptic proteins preferentially expressed by
      inhibitory and excitatory hippocampal neurons respectively. We previously
      reported decreased hippocampal formation cx mRNA and protein expression in
      schizophrenia, with a greater loss of cx II than cx I. The present in situ
      hybridization study was both an attempt at replication, and an extension to
      include bipolar and unipolar mood disorders, using sections from the Stanley
      Foundation brain series. In schizophrenia, both mRNAs were decreased in some
      hippocampal subfields, especially CA4, but were preserved in subiculum. The cx
      II/cx I mRNA ratio was unchanged. In bipolar disorder, the mRNAs were reduced in
      CA4, subiculum and parahippocampal gyrus, with the deficit in subiculum being
      diagnostically specific. No alterations in cx mRNAs were found in major
      depression. Treatment of rats with antipsychotics (haloperidol or chlorpromazine)
      for 2 weeks had no effect on hippocampal cx mRNAs. These data replicate the
      finding of decreased cx I and cx II expression in the hippocampus in
      schizophrenia and show a similar or greater abnormality in bipolar disorder. Non
      replication of the cx II > cx I mRNA loss in schizophrenia means that the
      hypothesis of a preferential involvement of excitatory connections was not
      supported. The results extend the emerging evidence that altered circuitry may be
      a component of the neuroanatomy of both schizophrenia and bipolar mood disorder.

PMID- 10889555
TI  - Mutation and association analysis of the 5' region of the dopamine D3 receptor
      gene in schizophrenia patients: identification of the Ala38Thr polymorphism and
      suggested association between DRD3 haplotypes and schizophrenia.
AB  - Although the association between the Ser9Gly polymorphism of the dopamine D3
      receptor gene (DRD3) and schizophrenia has been investigated by many research
      groups, it is not known whether the Ser9Gly polymorphism alone or a variation in
      linkage disequilibrium may effect susceptibility to schizophrenia. We searched
      the 5' region of the DRD3 gene and found three novel polymorphisms: -712G/C, 
      205A/G, and Ala38Thr. The Ala38Thr polymorphism is located in the first
      transmembrane region and is conserved in the monkey, mouse, and rat. Case-control
      comparisons in 153 Japanese schizophrenia patients and 122 Japanese controls did
      not suggest an association between Ala38Thr and schizophrenia. However, there was
      a marginally significant association between the Ser9 allele of the Ser9Gly
      polymorphisms and schizophrenia (P = 0.02). Furthermore, there was a highly
      significant association between haplotypes of the -712G/C, -205A/G, and Ser9Gly
      polymorphisms and schizophrenia (P = 0.0007, corrected P = 0.007). These positive
      findings were replicated in an additional 99 Japanese schizophrenia patients and
      132 controls (P = 0.04 and 0.0004, respectively). The most allelic differences of
      the Ser9Gly polymorphism between patient and control groups arose from the
      chromosome carrying specific alleles of the other three polymorphisms. This study
      indicates unknown variant(s) in linkage disequilibrium with the DRD3 haplotypes
      associated with schizophrenia.

PMID- 10889556
TI  - Allelic distribution of CTG18.1 in Caucasian populations: association studies in
      bipolar disorder, schizophrenia, and ataxia.
AB  - CTG18.1 is a highly polymorphic and unstable CTG repeat within an intron of the
      SEF2-1 gene. We tested the CTG18.1 repeat length in affective disorder,
      schizophrenia, and nonspecific ataxia; these diseases all have shown clinical
      evidence for anticipation. There was no difference in the allele frequencies
      comparing the controls and disease groups. The most common allele contains 11
      CAGs (35%) followed by alleles with 14-17 CAGs (35%). There was no difference in
      the distribution of the alleles in the cases vs controls for ataxia (P = 0.11),
      affective disorders (P = 0.21), or schizophrenia (P = 0.26). The frequency of
      unstable CTG18.1 alleles was approximately 3% in a population of N. European
      descent and is not related to the phenotypes tested.

PMID- 10889557
TI  - Function of the C-36 to T polymorphism in the human cholecystokinin gene
      promoter.
AB  - Cholecystokinin (CCK) is the most abundant neuropeptide in the mammalian brain,
      and in man significant quantities are expressed in all regions of the brain.1,2
      Therefore, CCK has been implicated in a variety of CNS functions-such as feeding
      behavior, anxiety, analgesia and memory functions as well as psychiatric disease
      like panic disorder and schizophrenia (for review, see2,3). Recently, a number of
      studies have indicated that a C-36 to T transition in the CCK gene promoter Sp1
      element4 (Figure 1) is associated with alcoholism and withdrawal symptoms as well
      as panic disorder.5-7 Moreover, it has been proposed that the polymorphism plays
      a direct role in the pathogenesis of the disorders by decreasing the expression
      and synthesis of CCK peptides. The significance of these findings is still
      unclear and other studies have failed to demonstrate linkage between the
      polymorphism and alcoholism.8 In this study we examined the function of the C-36
      to T transition in transcription of the human CCK gene. We demonstrate that
      substitution of the C-36 residue causes a slight reduction of Sp1 and Sp3
      binding, but this has no effect on transcription in vivo. Moreover, no difference
      in the response to physiological stimuli was observed. Taken together the results
      show that the C to T polymorphism does not play a direct role in the pathogenesis
      of either alcoholism or panic disorder and that a putative association to these
      disorders is likely to be the result of co-segregation with a linked mutation.

PMID- 10889558
TI  - The first, second, third and fourth order Markov chain analysis on the amino-acid
      sequence of human dopamine beta-hydroxylase.
AB  - The repeated amino-acid sequences in human dopamine beta-hydroxylase (DBH) may be
      indispensable for DBH activity, because such repetitions cannot be simply
      attributed to random chance. The amino acid sequence of human DBH was analysed
      according to two-, three-, four- and five-amino-acid sequences and their
      probabilities in human DBH were calculated. The first, second, third and fourth
      order Markov chain was used to calculate the transition probability for two-,
      three-, four- and five-amino-acid sequences. The longest repeated sequence is
      glycine-isoleucine-leucine-glutamic acid-glutamic acid, which appears twice in
      DBH. The results suggest that the amino acids with a high Markov transition
      probability may serve as the potential targets of new drugs, because they are
      unlikely to change into other amino acids.

PMID- 10889560
TI  - Family-based linkage disequilibrium mapping using SNP marker haplotypes:
      application to a potential locus for schizophrenia at chromosome 22q11
AB  - Mol Psychiatry 2000; 5: 77-84

PMID- 10889559
TI  - Association between variants at the GABAAbeta2, GABAAalpha6 and GABAAgamma2 gene
      cluster and alcohol dependence in a scottish population
AB  - Mol Psychiatry 1999; 4: 539-544

PMID- 10889561
TI  - Megacolon in patients with chronic spinal cord injury.
AB  - PURPOSE: To investigate the clinical and functional correlates of megacolon in
      individuals with chronic spinal cord injury (SCI). PATIENTS AND METHODS: This is
      a cross-sectional study of 128 patients consecutively admitted to a SCI in
      patient service in a US Veterans Administration Medical Centre (mean age 57+/-15
      years, mean years since injury 20+/-13, 97% male) who underwent plain abdominal
      radiography for study purposes. Participants were characterised by radiological
      findings. 'Megacolon' was defined as colonic dilatation of >6 cms in one or more
      colonic segment(s). Clinical, functional, and medication data were abstracted
      from the medical and nursing records. Individual interviews were conducted with
      study participants regarding bowel-related symptoms and treatment over the
      previous 1-month period. RESULTS: Seventy-three per cent of subjects (n=94) had
      megacolon, and 52% of these individuals had associated radiological constipation.
      Subjects with megacolon were compared with those without colonic dilatation
      (n=34). Factors significantly associated with megacolon were older age, longer
      duration of injury, symptom of abdominal distension, radiological constipation,
      urinary outlet surgery, laxative use at least once weekly, use of anticholinergic
      drugs, and use of calcium-containing antacids. These factors were simultaneously
      included in a multiple logistic regression model. Independent correlates of
      megacolon were more than 10 years elapsed since acute injury, age over 50 years,
      and use of >/=4 laxative doses per month. CONCLUSION: Megacolon is a highly
      prevalent disorder in individuals with chronic spinal cord injury. Our findings
      suggest that the presence of megacolon may be predicted in older individuals, and
      in those who are more than 10 years post-SCI. We also found that clinical
      constipation was frequently present in individuals with megacolon, despite their
      significantly greater use of laxatives. SPONSORSHIP: This work was supported by a
      grant from the Claude D Pepper Geriatric Research and Training Center from the
      National Institute of Ageing-AG08812-05, and a grant from the Education and
      Training Foundation of the Paralyzed Veterans Association in the USA. Dr Harari
      is currently recipient of a grant from Action Research (UK). Spinal Cord (2000)
      38, 331 - 339.

PMID- 10889562
TI  - Peak and kinetic cardiorespiratory responses during arm and leg exercise in
      patients with spinal cord injury.
AB  - STUDY DESIGN: A paired comparison of the peak and submaximal responses of oxygen
      uptake and heart rate in patients with spinal cord injury (SCI) performing
      voluntary arm cycle exercise and functional electrical stimulation (FES) leg
      cycling exercise. OBJECTIVES: To test if the blunted heart rate response and
      slower rate of adjustment of oxygen uptake seen in patients with SCI performing
      FES leg cycle exercise are also characteristic of arm exercise in these patients.
      METHODS: Eight paraplegics performed incremental and constant work rate (CWR)
      exercise with the legs and arms. Mean response times (MRT) for Vo2 during
      exercise (on) and in recovery (off) were calculated from the breath-by-breath Vo2
      profile. RESULTS: Peak heart rate was higher during incremental arm exercise, and
      uncorrelated with that observed during incremental FES leg cycling. For the same
      increase in Vo2, constant work rate arm exercise was associated with faster (and
      normal) Vo2 kinetics, greater increase in heart rate, and lower end-exercise
      blood lactate, compared to FES leg cycling. CONCLUSIONS: The consistently higher
      peak heart rate and Vo2, and faster Vo2 kinetics, for voluntary arm compared to
      FES leg cycle exercise suggest no intrinsic dysfunction of heart rate control in
      these paraplegics. Rather, these data suggest that during FES leg cycling the
      changes seen are due to some characteristic specific to the injury, such as
      reduced muscle mass and/or deconditioning of the remaining muscle. SPONSORSHIP:
      This research was supported by The Department of Veterans Affairs, Rehabilitation
      Research and Development Project #B603-RA. Spinal Cord (2000) 38, 340 - 345.

PMID- 10889563
TI  - Current trend and risk factors for kidney stones in persons with spinal cord
      injury: a longitudinal study.
AB  - STUDY DESIGN: A multi-center longitudinal study. OBJECTIVES: To estimate the
      current trend in the incidence of first kidney stone among persons with spinal
      cord injury (SCI) and to delineate the potential contributing factors. SETTING:
      Twenty-one Model SCI Care Systems throughout the United States. METHODS: A
      longitudinal cohort of 8314 subjects enrolled in the National SCI Database
      between 1986 and 1999 was used to estimate and compare the incidence of first
      kidney stone with a previous report of 5850 SCI patients injured between 1973 and
      1982. A Cox regression analysis was performed to identify risk factors for
      stones, including age, race, gender, severity of injury, and method of urinary
      drainage. These variables have been routinely collected, on a yearly basis, by
      the collaborating SCI centers. RESULTS: During the 12 years, 6 months of case
      ascertainment, 286 incident stone cases were documented. The risk was greatest
      during the first 3 months after injury (31 cases per 1000 person-years), quickly
      decreasing and leveling off later (eight cases per 1000 person-years). It was
      estimated that within 10 years after injury, 7% of persons with SCI would develop
      their first kidney stone. There was no evidence that the risk has changed over
      the past 25 years (P=0.96). During the first year post injury only, a
      significantly increased risk of stones was observed in Caucasians and persons
      aged 45 years or older. A positive association of the severity of injury and
      requiring instrumentation for bladder emptying with kidney stones was found after
      the first year post injury. The type of urinary drainage, including indwelling,
      intermittent, and condom catheterization, had no significant differential effect
      on stone formation at either risk period. CONCLUSIONS: The highest risk of kidney
      stones is within the first few months post injury. Little progress has been made
      in reducing this risk. Although inability to control bladder function is an
      important risk factor after the first year post injury, for those who need
      bladder management, the type of urinary drainage does not appear to be an
      important factor in determining risk. Spinal Cord (2000) 38, 346 - 353.

PMID- 10889564
TI  - Kinematics of prehension and pointing movements in C6 quadriplegic patients.
AB  - AIMS: C6 quadriplegic patients lack voluntary control of their triceps muscle but
      can still perform reaching movements to grasp objects or point to targets. The
      present study documents the kinematic properties of reaching in these patients.
      MATERIALS AND METHODS: We investigated the kinematics of prehension and pointing
      movements in four quadriplegic patients and five control subjects. Prehension and
      pointing movements were recorded for each subject using various object positions
      (ie different directions and distances from the subject). The 3D motion was
      analyzed with Fastrack Polhemus sensors. RESULTS: During prehension tasks the
      velocity profile of control subjects showed two peaks (go and return); the first
      velocity peak was scaled to the distance of the object. In quadriplegic patients
      there was a third intermediary peak corresponding to the grasping of the object.
      The amplitude of the first peak was slightly smaller than in control subjects.
      Velocity was scaled to the distance of the object, but with a greater dispersion
      than in control subjects. Total movement time was longer in quadriplegics because
      of the prolonged grasping phase. There were few differences in the pointing
      movements of normal and quadriplegic subjects. The scapula contributed more to
      the reaching phase of both movements in quadriplegic patients. CONCLUSION: In
      spite of some quantitative differences, the kinematics of the hand during
      reaching and pointing in quadriplegic patients are surprisingly similar to those
      of control subjects. Spinal Cord (2000) 38, 354 - 362.

PMID- 10889565
TI  - Quality of life in patients with spinal cord injury receiving Viagra (sildenafil
      citrate) for the treatment of erectile dysfunction.
AB  - STUDY DESIGN: A multicenter, randomized, double-blind, placebo-controlled,
      flexible-dose, two-way crossover study conducted June 1996 through January 1997.
      OBJECTIVES: To evaluate the effect of sildenafil citrate (VIAGRA(R)) on the
      quality of life (QoL) of men with erectile dysfunction (ED) caused by spinal cord
      injury (SCI). SETTING: Study centers in Australia, Belgium, France, Germany,
      Norway, Sweden and the United Kingdom. METHODS: Questions 13 and 14 of the 15
      item International Index of Erectile Function (IIEF) addressed QoL issues
      directly related to ED in 178 men with SCI. A 5-item questionnaire addressing
      concerns that men had about their erection problems was also used to evaluate the
      impact of ED on QoL. Several commonly used psychometric instruments, including
      the Medical Outcomes Survey (MOS) Short Form-12, Psychological General Well-Being
      Index, and MOS Family Survey, assessed general QoL issues. RESULTS: Significant
      improvements were seen for overall satisfaction with sex life (IIEF Q13), sexual
      relationship with partner (IIEF Q14), and concerns about erectile problems
      (P<0.0001). Improvements were reported in scores for the generic QoL parameters
      of mental health, well-being, depression, and anxiety (P<0.05 sildenafil versus
      placebo). CONCLUSION: Treatment with sildenafil can significantly improve key QoL
      parameters in men with ED caused by SCI. SPONSORSHIP: This study was funded by
      Pfizer Inc. Spinal Cord (2000) 38, 363 - 370.

PMID- 10889566
TI  - Hospital readmissions in people with chronic spinal cord injury.
AB  - STUDY DESIGN: Longitudinal observational. OBJECTIVES: To examine frequency and
      duration of hospital readmissions in a population based sample of people with
      chronic spinal cord injury (SCI) and to look at medical reasons necessitating
      readmissions and factors influencing them. SETTING: National Spinal Injuries
      Centre, Stoke Mandeville Hospital, Aylesbury, UK and Regional Spinal Injuries
      Centre, District General Hospital, Southport, UK. METHODS: One-hundred-and-ninety
      eight SCI patients, all injured more than 20 years ago, were interviewed on three
      occasions and their medical records reviewed for the period 1990 - 1996. RESULTS:
      Between 1990 and 1996, 127 patients (64% of the sample) required hospital
      treatment for late medical complications, with 481 readmissions between them and
      the mean length of stay of 12.03 days per readmission. Only 58% of all
      readmissions were into specialised spinal injuries centres. Averaged over the
      entire sample, the readmission rate was 0.4 readmissions per person at risk per
      year, and the occupancy rate was 4.9 bed-days per person at risk per year. The
      most frequent reason for readmissions were urinary tract complications (40.5% of
      all readmissions) and the highest bed occupancy was for skin problems (32.2% of
      all bed-days). When compared with the non-hospitalised group (36% of the sample),
      the readmitted patients had longer duration of paralysis and lower disability and
      handicap scores as measured by Functional Independence Measure (FIM) and Craig
      Handicap Assessment & Reporting Technique (CHART). The subgroups did not differ
      significantly by neurological grouping or age. CONCLUSIONS: Urinary and skin
      complications are the two main reasons for hospital readmissions in people with
      chronic SCI. Risk of readmissions increases with time since injury and with
      disability and handicap severity. Hospital bed requirements for people with
      chronic SCI are greater than the amount of clinical provision currently available
      in specialised spinal centres. In order to meet the needs of the growing SCI
      population, more specialised spinal injuries care beds will be needed. Spinal
      Cord (2000) 38, 371 - 377.

PMID- 10889567
TI  - Secretory immunoglobulin A in the vesical urothelium of patients with neuropathic
      bladder--an immunohistochemical study.
AB  - STUDY DESIGN: A pilot study was carried out on archival material of bladder
      biopsies taken during 1994 and 1995 from patients with neuropathic bladder.
      OBJECTIVES: To compare the pattern of immunostaining for sIgA in the urothelium
      of biopsies taken from neuropathic bladder with the biopsies obtained from
      patients with non-neuropathic bladders. SETTING: Regional Spinal Injuries Centre,
      Southport and Department of Pathology, Royal Liverpool University Hospital,
      Liverpool. METHODS: Formalin-fixed, paraffin-embedded biopsies of bladder mucosa
      taken from patients with neuropathic urinary bladder (n=43) during 1994 and 1995
      were processed for immunostaining with rabbit polyclonal antibody for secretory
      component of IgA. Archival specimens of bladder biopsies from non-neuropathic
      bladder were stained as controls. All sections were stained contemporaneously.
      RESULTS: In all the control biopsies, strong immunostaining for sIgA was observed
      in the superficial cells of transitional epithelium. In the biopsies taken from
      patients with neuropathic bladder, immunostaining in the transitional epithelium
      was variable: strong in 14 cases; moderate in four; faint in 16; and absent in
      three. Immunostaining for sIgA was absent in all the five biopsies in which the
      urothelium had undergone squamous metaplasia. One biopsy showed intestinal
      metaplasia; immunostaining for sIgA was seen in the basal cells. CONCLUSION:
      Strong immunostaining for sIgA was observed in the urothelium of all biopsies
      taken from non-neuropathic bladder. In contrast to this, only 18 of 37 biopsies
      obtained from neuropathic bladder showed strong or moderate immunostaining for
      sIgA in the transitional epithelium. Spinal Cord (2000) 38, 378 - 381.

PMID- 10889568
TI  - Total en-bloc spondylectomy for correcting congenital kyphosis.
AB  - STUDY DESIGN: A case report of congenital kyphosis corrected using a total en
      bloc spondylectomy. OBJECTIVES: To report a new surgical technique for the
      treatment of congenital kyphosis with myelopathy. SETTING: Department of
      Orthopedic Surgery, Akita University School of Medicine, Akita, Japan. METHODS: A
      16-year-old boy who showed a 61 degrees angular kyphosis and a 32 degrees
      scoliosis from T6 to T9 due to the failure of the vertebral bodies formation in
      T7 and T8 was treated with a total en-bloc spondylectomy. RESULTS: The kyphosis
      was corrected to 26 degrees (57.3%) and the scoliosis was corrected to 5 degrees
      (84.4%) postoperatively. Three years postoperatively, no loss of correction has
      occurred and the patient has no complaints. CONCLUSIONS: Total en-bloc
      spondylectomy is one of the useful surgical procedures for correction of
      congenital kyphosis Type I, with a high correction rate. Spinal Cord (2000) 38,
      382 - 385.

PMID- 10889569
TI  - Vitiligo management update.
AB  - Vitiligo is an acquired skin disorder caused by the disappearance of pigment
      cells from the epidermis, and results in well defined white patches that are
      often symmetrically distributed. The lack of melanin pigment makes the lesional
      skin more sensitive to sunburn. Vitiligo can be cosmetically disfiguring and is a
      stigmatizing condition, leading to serious psychological problems in daily life.
      It occurs worldwide in about 1% of the population, mostly between the ages of 10
      30 years, and as often in males as in females. The cause is unknown, but might
      involve genetic factors, autoimmunity, toxic metabolites, and/or a higher
      vulnerability of melanocytes. Some new treatments for this condition include
      corticosteroid + UVA treatment, UVB narrow wave band (311 nm) irradiation, and
      transplantation of autologous pigment cells. In widespread vitiligo, residual
      pigment can be removed by depigmentation agents. Sunscreens, camouflage products
      and good guidance may help the patient to better cope with this disease.

PMID- 10889570
TI  - Current therapy in Behcet's disease.
AB  - Behcet's disease is an inflammatory disorder of unknown cause. There is often
      involvement of the gastrointestinal system, the central nervous system and large
      vessels, which can be life-threatening. As well, ocular lesions can cause
      blindness. Mucocutaneous symptoms are self-limiting but more frequent. Almost all
      the patients have recurrent oral aphthous ulcers, and more than 70% of the
      patients have genital ulcers and skin symptoms, which include erythema nodosum,
      pseudofolliculitis, papulopustular lesions, acneiform nodules and a positive
      pathergy test. The pathergy test is felt to reflect cutaneous hypersensitivity.
      In general, topical treatment using corticosteroids is satisfactory for these
      mucocutaneous lesions unless eye and vital organs are involved.

PMID- 10889571
TI  - A piece of my mind: I held him in my arms and wept.

PMID- 10889572
TI  - JAMA 100 years ago: DISSEMINATION OF BACTERIA FROM THE MOUTH DURING SPEAKING,
      COUGHING, AND OTHERWISE

PMID- 10889573
TI  - AIDS in South Africa takes center stage.

PMID- 10889576
TI  - The world in medicine: HIV drug resistance

PMID- 10889574
TI  - Rural HIV/AIDS in the United States: studies suggest presence, no rampant spread.

PMID- 10889577
TI  - The world in medicine: breathing easier

PMID- 10889578
TI  - The world in medicine: blood flow during REM

PMID- 10889579
TI  - The world in medicine: public health meets the streets

PMID- 10889580
TI  - Exercise regimens for men with HIV.

PMID- 10889581
TI  - Exercise regimens for men with HIV

PMID- 10889582
TI  - Resistance exercise and oxandrolone for men with HIV-related weight loss.

PMID- 10889584
TI  - Resistance exercise and oxandrolone for men with HIV-related weight loss

PMID- 10889583
TI  - Resistance exercise and oxandrolone for men with HIV-related weight loss.

PMID- 10889585
TI  - Plaque morphology as a risk factor for stroke.

PMID- 10889586
TI  - Plaque morphology as a risk factor for stroke

PMID- 10889587
TI  - Quality of life in maintenance vs prolonged induction therapy for HIV.

PMID- 10889588
TI  - Directly observed therapy to treat HIV infection in prisoners.

PMID- 10889589
TI  - Lead exposure from candles.

PMID- 10889590
TI  - Supplemental oxygen and mountaineer death rates on Everest and K2.

PMID- 10889591
TI  - Immunologic and virologic effects of subcutaneous interleukin 2 in combination
      with antiretroviral therapy: A randomized controlled trial.
AB  - CONTEXT: While interleukin 2 (IL-2) is capable of inducing a marked expansion of
      the CD4 T-lymphocyte pool, limited data exist on whether IL-2 treatment can add
      significantly to the immunologic and virologic effects of potent antiretroviral
      therapy (ART). OBJECTIVE: To determine the rate and magnitude of CD4 cell
      recovery and viral suppression when using a combination therapy of IL-2 and ART
      compared with ART alone. DESIGN AND SETTING: Randomized, controlled multicenter
      trial conducted from April 1996 through April 1998 at 8 clinical sites in the
      United States. PATIENTS: Eighty-two adult outpatients who were infected with
      human immunodeficiency virus (HIV) and had baseline CD4 cell counts of 200 x
      10(6)/L to 500 x 10(6)/L and baseline RNA levels of fewer than 10,000 copies/mL
      were randomized; 78 completed the study. INTERVENTIONS: Thirty-nine patients were
      randomly assigned to receive a combination therapy of subcutaneous IL-2
      (administered in 5-day courses every 8 weeks at a starting dosage of 7.5 mIU
      twice per day) and ART; 43 were to receive ART therapy alone. MAIN OUTCOME
      MEASURES: Interleukin 2 safety and differential effects on CD4 cell counts, CD4
      cell percentages, and plasma HIV RNA levels. RESULTS: The mean (SD) percentage
      increase in CD4 cell counts at 1 year for patients who received IL-2 was 112%
      (113%) compared with 18% (35%) in recipients of ART alone (P<.001). Both groups
      had mean (SD) increases in CD4 cell percentage: from 20.4% (6.3%) to 32.3%
      (12.4%) for the combination therapy group compared with 20.4% (5.1%) to 23.0%
      (7.2%) for recipients of ART alone (P<.001). Using a sensitive viral RNA assay,
      mean viral load changes were -0.28 and 0.09 log(10) copies for IL-2 recipients
      and control patients, respectively (P=.03). Twenty (67%) of 30 evaluable patients
      receiving IL-2 achieved final viral loads of fewer than 50 copies/mL compared
      with 13 (36%) of 36 control patients (P=.02). Toxic effects were common among
      patients who received IL-2 and were managed with antipyretics, hydration, rest,
      and dosage reduction as needed. CONCLUSIONS: Intermittent therapy with IL-2 and
      ART produced a substantially greater increase in CD4 cells and was associated
      with a larger decrease in viral load than ART alone. Clinical end-point trials
      will be necessary to determine whether the enhanced viral suppression and CD4
      cell increases associated with IL-2 therapy will translate into improved clinical
      outcomes. JAMA. 2000;284:183-189

PMID- 10889592
TI  - Reduction in mortality with availability of antiretroviral therapy for children
      with perinatal HIV-1 infection. Italian Register for HIV Infection in Children
      and the Italian National AIDS Registry.
AB  - CONTEXT: Since the introduction of combined antiretroviral therapy, mortality
      rates in adults with human immunodeficiency virus type 1 (HIV-1) infection have
      decreased. However, little information is available outside the setting of
      controlled trials on survival of perinatally HIV-infected children treated with
      antiretroviral therapy. OBJECTIVE: To assess effect of availability of
      antiretroviral therapy on decreasing mortality in perinatally HIV-infected
      children. DESIGN: Population-based, multicenter longitudinal study involving data
      collected by the Italian Register for HIV Infection in Children. SETTING: A
      network of 106 pediatric clinical centers. SUBJECTS: A total of 1142 children
      born between November 1980 and December 1997 with perinatally acquired HIV
      infection with a median follow-up of 5.9 years. MAIN OUTCOME MEASURE: Time to HIV
      related death calculated for birth cohort and calendar period and grouped by
      distribution of predominant type of antiretroviral therapy administered over
      time. RESULTS: Survival was longer in the 1996-1997 birth cohort (crude relative
      hazard [RH] of death, 0.39; 95% confidence interval [CI], 0.15-0.96) and 1996
      1998 calendar period (crude RH of death, 0.65; 95% CI, 0.45-0.95) than in birth
      cohort and calendar period 1980-1995, but not when adjusted for maternal
      antiretroviral treatment during pregnancy and clinical condition at time of
      delivery, gestational age, and birth weight (adjusted RH of death, 0.55; 95% CI,
      0.20-1.50, for birth cohort; and adjusted RH of death, 0.71, 95% CI, 0.43-1.16,
      for calendar period). In a multivariate model with 1980-1995 as comparison, the
      1996-1997 birth cohort had an RH of 0.57 (95% CI, 0.22-1.47; P=.27) but RH for
      calendar period 1996-1998 was 0.63 (95% CI, 0.47-0.85; P<. 01). When the effects
      of birth cohort, calendar period, and type of antiretroviral therapy were
      evaluated simultaneously in the same model, the RH of death was not significantly
      different from 1.0 for the 1996-1997 birth cohort (P=.19) and calendar period
      1996-1998 (P=. 83) suggesting a causal relationship between decreased risk of
      death and use of combination therapy. The RH of death in children receiving
      monotherapy or double or triple combination therapy was 0. 77 (95% CI, 0.55
      1.08), 0.70 (95% CI, 0.42-1.17), and 0.29 (95% CI, 0.13-0.67), respectively, vs
      no antiretroviral therapy. CONCLUSION: Survival of perinatally HIV-infected
      children improved in 1996-1998 as a result of the introduction of combined
      antiretroviral therapies. JAMA. 2000;284:190-197

PMID- 10889593
TI  - HIV prevalence and associated risks in young men who have sex with men. Young
      Men's Survey Study Group.
AB  - CONTEXT: Studies conducted in the late 1980s on human immunodeficiency virus
      (HIV) infection among older men who have sex with men (MSM) suggested the
      epidemic had peaked; however, more recent studies in younger MSM have suggested
      continued high HIV incidence. OBJECTIVE: To investigate the current state of the
      HIV epidemic among adolescent and young adult MSM in the United States by
      assessing the prevalence of HIV infection and associated risks in this population
      in metropolitan areas. DESIGN: The Young Men's Survey, a cross-sectional,
      multisite, venue-based survey conducted from 1994 through 1998. SETTING: One
      hundred ninety-four public venues frequented by young MSM in Baltimore, Md;
      Dallas, Tex; Los Angeles, Calif; Miami, Fla; New York, NY; the San Francisco
      (Calif) Bay Area; and Seattle, Wash. SUBJECTS: A total of 3492 15- to 22-year-old
      MSM who consented to an interview and HIV testing. MAIN OUTCOME MEASURES:
      Prevalence of HIV infection and associated characteristics and risk behaviors.
      RESULTS: Prevalence of HIV infection was high (overall, 7.2%; range for the 7
      areas, 2.2%-12. 1%) and increased with age, from 0% among 15-year-olds to 9.7%
      among 22-year-olds. Multivariate-adjusted HIV infection prevalence was higher
      among blacks (odds ratio [OR], 6.3; 95% confidence interval [CI], 4.1-9.8), young
      men of mixed or other race (OR, 4.8; 95% CI, 3. 0-7.6), and Hispanics (OR, 2.3;
      95% CI, 1.5-3.4), compared with whites (referent) and Asian Americans and Pacific
      Islanders (OR, 1. 1; 95% CI, 0.5-2.8). Factors most strongly associated with HIV
      infection were being black, mixed, or other race; having ever had anal sex with a
      man (OR, 5.0; 95% CI, 1.8-13.8); or having had sex with 20 or more men (OR, 3.0;
      95% CI, 2.0-4.7). Only 46 (18%) of the 249 HIV-positive men knew they were
      infected before this testing; 37 (15%) were receiving medical care for HIV, and
      19 (8%) were receiving medical drug therapy for HIV. Prevalence of unprotected
      anal sex during the past 6 months was high (overall, 41%; range, 33%-49%).
      CONCLUSIONS: Among these young MSM, HIV prevalence was high, underscoring the
      need to evaluate and intensify prevention efforts for young MSM, particularly
      blacks, men of mixed race or ethnicity, Hispanics, and adolescents. JAMA.
      2000;284:198-204

PMID- 10889594
TI  - Risk of cancer in children with AIDS. AIDS-Cancer Match Registry Study Group.
AB  - CONTEXT: Population-based data on cancers associated with acquired
      immunodeficiency syndrome (AIDS) in children are lacking. OBJECTIVE: To determine
      risk of pediatric AIDS-associated cancers. DESIGN, SETTING, AND PARTICIPANTS:
      Using records from 11 locations in the United States for varying periods between
      1978 and 1996, we linked data for children aged 14 years and younger at AIDS
      diagnosis to local cancer registry data. MAIN OUTCOME MEASURES: Cancer frequency
      and, in the 2-year post-AIDS onset period, cancer incidence and relative risk
      (RR; measured as standardized incidence ratio), by cancer type. RESULTS: Among
      4954 children with AIDS, 124 (2.5%) were identified as having cancer before, at,
      or after AIDS onset, including 100 cases of non-Hodgkin lymphoma (NHL), 8 of
      Kaposi sarcoma (KS), 4 of leiomyosarcoma, and 2 of Hodgkin disease; there were 10
      other or unspecified cancers. Expected numbers for all cancers identified in the
      study sample, based on population rates (using area-specific registry data), were
      less than 1. In the first 2 years after AIDS diagnosis (5485 person-years), NHL
      incidence was 510 per 100,000 person-years (RR, 651; 95% confidence interval
      [CI], 432-941). Median time for developing NHL after AIDS diagnosis was 14 months
      (range, 3-107 months). The most common type of NHL was Burkitt lymphoma. However,
      the risk of primary brain lymphoma (91 per 100,000 person-years) was especially
      high (RR, 7143; 95% CI, 2321-16,692), and 4 cases were diagnosed more than 2
      years (range, 37-98 months) after AIDS onset. Leiomyosarcomas also tended to
      occur several years after AIDS onset, with 3 of the 4 cases occurring 33 to 76
      months after AIDS diagnosis, whereas KS was reported only at or within 2 years of
      AIDS diagnosis. Hodgkin disease risk was also significantly increased (RR, 62;
      95% CI, 2-342). CONCLUSIONS: The spectrum of AIDS-associated pediatric cancers
      resembled that seen in adults, with the addition of leiomyosarcoma. Both primary
      brain lymphomas and leiomyosarcomas tended to occur in children surviving several
      years after AIDS onset. Because the expected numbers of these cancers in this
      population were less than 1 and because of the small numbers of some types of
      observed cancers, the RR estimates are imprecise and caution is warranted in
      their interpretation. JAMA. 2000;284:205-209

PMID- 10889595
TI  - Failure of routine HIV-1 tests in a case involving transmission with
      preseroconversion blood components during the infectious window period.
AB  - CONTEXT: Current screening practices for blood donations have been successful in
      reducing human immunodeficiency virus (HIV) transmission through receipt of
      contaminated blood products. However, HIV-infected blood donations made prior to
      seroconversion and before high levels of viral replication occur could test
      negative using both serologic antigen and antibody tests. Testing based on
      nucleic acid amplification (NAT) is being implemented to screen for HIV-infected
      blood donated during this period, yet the issue of single vs minipool donation
      screening remains unresolved. OBJECTIVES: To determine HIV-1 genetic linkage
      between virus in 2 HIV-1-infected recipients of blood components and virus in the
      donor, who was HIV antigen and antibody negative at the time of donation; to
      screen the blood donor's plasma with HIV NAT assays, including those currently
      proposed for use in US blood donation screening. DESIGN AND SETTING: Case study
      conducted in October 1997 involving the Communicable Disease Centre, Singapore
      General Hospital, and the Singapore Blood Transfusion Service, Singapore.
      SUBJECTS: The blood donor and the 2 recipients of donor platelets and red blood
      cells. MAIN OUTCOME MEASURES: Genetic analysis of the HIV-1 p17 coding region of
      gag and the C2V5 region of env to determine the genetic relatedness of virus from
      the donor and recipients; reactivity in quantitative and qualitative assays, and
      reactivity in donor screening HIV NAT assays in single donation and minipool
      screening contexts. RESULTS: Direct DNA sequencing demonstrated identical HIV-1
      subtype E viral sequences in the donor and recipients. Based on comparisons of a
      qualitative and quantitative assay for HIV-1 RNA levels, a low level of viremia
      (range, 5-39 copies/mL in plasma) was estimated to be in the donor's undiluted
      blood at the time of donation. Additional testing using donor-screening NAT
      assays showed consistent detection of HIV RNA in the undiluted donor plasma
      whereas detection was inconsistent at the 1:16 and 1:24 dilution levels currently
      used in minipool screening of blood donations in the United States. CONCLUSIONS:
      Transmission of HIV from a blood donor to a platelet recipient and a red blood
      cell recipient occurred in the preseroconversion infectious window period. The
      viral load in the implicated donation was estimated to be less than 40 copies/mL
      of plasma. Current US minipool HIV NAT screening protocols may not be
      sufficiently sensitive to detect all infectious window-period donations. JAMA.
      2000;284:210-214

PMID- 10889596
TI  - Current evidence and future directions for targeting HIV entry: therapeutic and
      prophylactic strategies.
AB  - Great strides have been made in developing potent antiretroviral regimens that
      block human immunodeficiency virus (HIV) transcription and assembly. Despite
      these therapeutic advances, problems of drug resistance, latent viral reservoirs,
      and drug-induced toxic effects that compromise effective viral control point to
      the need for new classes of anti-HIV drugs with different modes of action. One
      promising approach involves blocking HIV entry into human cells, a complex
      process that involves multiple protein interactions. The process of HIV entry
      begins with binding of the viral envelope glycoprotein to both the CD4 receptor
      and one of several chemokine receptors and ends with fusion of viral and cell
      membranes. Conceptually, there are 3 steps in the HIV entry process that could
      serve as therapeutic targets: binding of the viral envelope glycoprotein with the
      CD4 receptor, binding of the envelope-CD4 complex to chemokine receptors, and
      fusion of the viral and cell membranes. Preclinical and clinical assessment of
      these entry inhibitors is ongoing and will determine if they possess properties
      required for drug licensure. Moreover, the worldwide epidemic is largely
      occurring in developing countries that cannot afford these drugs: a prophylactic
      vaccine is necessary and urgent. New knowledge of the HIV-envelope glycoprotein
      has also provided insight into possibilities for the design of novel HIV
      vaccines. JAMA. 2000;284:215-222

PMID- 10889597
TI  - Immune restoration with antiretroviral therapies: implications for clinical
      management.
AB  - Recent dramatic decreases in acquired immunodeficiency syndrome-related mortality
      are largely due to the introduction of highly active antiretroviral therapy
      (HAART). Although immune restoration due to suppression of human immunodeficiency
      virus (HIV) replication is a critical determinant of these trends, the magnitude
      of immune restoration seen after treatment with HAART varies substantially among
      treated persons and is generally incomplete. Nonetheless, even partial immune
      restoration is sufficient to provide protection from most major opportunistic
      infections; these risks can be largely predicted by the number of circulating CD4
      cells. Limited data suggest that treatment earlier during the course of HIV
      infection may result in greater preservation of immune function, though this has
      not been studied in great detail. Preliminary studies performed among persons
      with multidrug-resistant virus whose treatment regimens are failing suggest that
      there is likely a benefit to continuation of therapy that may be related to
      diminished pathogenicity of drug-resistant virus. As deaths related to
      opportunistic infections diminish, the spectrum of causes of mortality in HIV
      infection is changing. Except for Kaposi sarcoma, there is insufficient
      information to conclude that the risks of non-Hodgkin lymphoma and other
      malignancies are diminishing among persons with HIV infection. How much immune
      restoration will be enough to ensure long-term survival in persons with HIV
      infection remains an open question. JAMA. 2000;284:223-228

PMID- 10889598
TI  - Trends in incidence and prevalence of major transfusion-transmissible viral
      infections in US blood donors, 1991 to 1996. Retrovirus Epidemiology Donor Study
      (REDS)
AB  - CONTEXT: Evaluating trends in blood donor infectious disease rates is essential
      for monitoring blood supply safety and donor screening effectiveness. OBJECTIVE:
      To determine changes over time in blood donor population infection rates of human
      immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis C
      virus (HCV), and hepatitis B virus (HBV). DESIGN: Cross-sectional survey data
      from the National Heart, Lung, and Blood Institute-sponsored Retrovirus
      Epidemiology Donor Study. SETTING: Five blood centers in different regions of the
      United States. PARTICIPANTS: A total of 1.9 million volunteer blood donors with 1
      or more nonautologous donations from January 1991 to December 1996. MAIN OUTCOME
      MEASURES: Changes in rates of HIV, HTLV, HCV, and HBV infections were evaluated
      by comparing yearly prevalence estimates (per 100,000 donations) for first-time
      allogeneic donors and period-specific incidence rates (IRs) (per 100,000 person
      years) for repeat allogeneic donors between 1991 and 1996 (for HCV, from about
      March 1992 to June 1996). RESULTS: Prevalence of HIV decreased in first-time
      donors from 0.030% to 0.015% (P=.006) and HCV prevalence decreased from 0.63% to
      0.40% (P<.001). Trends were not statistically significant for the proportion of
      first-time donors with hepatitis B surface antigen (HBsAg) or HTLV. For repeat
      donors, IRs did not change significantly, indicating a stable but low level of
      seroconversion. The overall IRs (95% confidence intervals) per 100,000 person
      years were 2.92 (2.26-3.70) for HIV, 1.59 (1.12-2.19) for HTLV, 3.25 (2.36-4.36)
      for HCV, and an estimated 10.43 (7.99-13. 37) for HBV (based on an HBsAg rate of
      2.66 [2.04-3.41] with presumed false-positive results considered negative). The
      HBV IR estimate with presumed false-positive results considered positive (for
      comparability to previous analyses) was 17.83 (14.60-21.56). CONCLUSION: The
      decrease in HIV and HCV prevalence rates, combined with the previously documented
      lower rates of infection in first-time donors compared with the general
      population, suggests the continued benefit of behavioral risk factor screening.
      JAMA. 2000;284:229-235

PMID- 10889599
TI  - Interleukin 2 treatment for HIV infection.

PMID- 10889600
TI  - Will blood transfusion ever be safe enough?

PMID- 10889601
TI  - Diabetes insipidus: a current perspective.

PMID- 10889602
TI  - Thyrotoxic hypokalemic paralysis: a case study.

PMID- 10889603
TI  - Using a portable ultrasound bladder scanner in the cardiac care unit.

PMID- 10889604
TI  - Early enteral feeding of patients with multiple trauma.
AB  - The case study illustrates the recovery of a patient with multiple trauma who was
      fed a peptide-based formula via the enteral route soon after the trauma. Although
      the clinical course might have been worse if D.H. had not received this
      treatment, his generally excellent recovery might be partly attributable to this
      therapy. Although stress hypermetabolism occurs in most patients with multiple
      trauma within 48 hours after injury, no known treatment can arrest or reverse
      this problem. However, the lethal catabolic and septic effects of stress
      hypermetabolism can be at least partly thwarted through delivery of enteral
      nutrients within 72 hours after trauma.

PMID- 10889605
TI  - Continuous arteriovenous rewarming: a bedside technique.

PMID- 10889606
TI  - Caring for critically ill infants: strategies to promote physiological stability
      and improve developmental outcomes.
AB  - Promoting organization and delivering developmentally supportive care leads to
      improved outcomes for infants and their families. Critical care nurses must
      function as catalysts to expand the thinking of caregivers from a dimension
      consisting primarily of physiology to one that embraces the emotional and
      cognitive growth and well-being of the patient, the patient's family, and staff
      members. For critically ill infants, developmentally supportive care that is
      relationship based and that promotes the balance of organized neurobehavioral and
      physiological function is an avenue to achieve that end. Beneficial or adverse
      outcomes of nursing care used during this critical period can persist long after
      an infant is discharged from the intensive care setting.

PMID- 10889607
TI  - Alcohol-related thiamine deficiency and malnutrition.

PMID- 10889608
TI  - The Synergy Model in practice. Being a good dance partner.

PMID- 10889609
TI  - Monitoring pulmonary artery pressure.

PMID- 10889610
TI  - What is the recommended external reference point for zeroing an intracranial
      pressure monitoring system at the foramen of Monro?

PMID- 10889611
TI  - Family presence protocol can be a powerful healing force.

PMID- 10889612
TI  - [How well do patients' relatives evaluate and understand information provided by
      the intensive care unit?].
AB  - A study was made of the process of providing information to the relatives of
      critical patients admitted to a polyvalent ICU. Work was carried out by a group
      of nurses not usually responsible for informing patients or their relatives,
      which usually is the task of attending physicians. In intensive care, nurses
      should become more involved in the information process because they are in close
      contact with patients and their families. The specific objectives of the study
      were: 1. To study relatives' reaction to and acceptance of the information
      process. 2. To evaluate their perception of the quality of care. 3. To collect
      information for developing an information protocol that would assist nurses in
      communicating with relatives and informing them of the care and needs of the
      patient. An analysis was made of responses to an opinion survey obtained from the
      relatives of 180 patients who received medical information daily. The sample
      consisted of patients admitted on even numbered days. Results were favorable with
      regard to the level of satisfaction and understanding of the information given to
      relatives. However, they noted that the lack of privacy and courtesy worsened the
      perceived quality of care.

PMID- 10889614
TI  - [Care of a patient with leptospirosis icterohemorrhagica].
AB  - Leptospirosis is an acute generalized infectious disease caused by a spirochete
      of the genus Leptospira. Humans become infected by direct contact with the animal
      reservoir or indirectly through standing water or contaminated wet areas; once
      the leptospira has entered the body through the mucosa or eroded skin, it is
      spread by blood circulation. It can cause hepatic, renal and muscular disorders,
      as well as meningeal inflammation. We report the case of a patient admitted to
      the ICU for an infectious process produced by leptospira. Complications are
      described and identified as nursing problems and/or diagnoses. Following the
      NANDA nomenclature, the diagnoses were: Tissue-perfusion disturbance.
      Deterioration of gas exchange. Deterioration of verbal communication. Nutritional
      disorder. These categories enabled specific nursing interventions to be planned
      for the patient's care. The patient died of multiple organ failure in spite of
      conventional care and treatment.

PMID- 10889613
TI  - [Patients' sleep in intensive care units and sleep-modifying factors].
AB  - Patients admitted to intensive care units sleep poorly, generally because of the
      environmental conditions of these units. Sleep deprivation in critical patients
      has severe consequences and can contribute to deterioration of their condition.
      The quality of sleep of the patients in our unit was evaluated to identify
      factors that they considered disruptive of sleep. The study included 33 patients
      who were admitted between April 1998 and January 1999 and had remained conscious
      and oriented for at least 5 days before being included in the study. We asked
      them to evaluate how well they had slept during their stay in the unit and to
      score specific factors that could disrupt sleep (environment, admission to the
      unit, techniques and procedures) on a scale of 0 to 10. Most patients (63.6%)
      claimed that they "always" or "usually" slept well. The most disruptive
      environmental factor was the sound of alarms, pain bothered patients more than
      fear or anxiety, and endotracheal intubation and mechanical ventilation were the
      techniques that most interfered with sleep. The quality of sleep of patients in
      the unit was apparently uninfluenced by pre-admission sleep problems, the
      severity of the process, or the type of analgesia-sedation administered. The
      largest percentage of patients who slept poorly had been admitted to one of the
      wings of the unit, which should be studied specifically.

PMID- 10889615
TI  - The Robert Tiffany Annual Nursing Lecture 14 June 1999: moving oncology nursing
      forward, an agenda for the 21st century.

PMID- 10889616
TI  - Diagnostic delays in head and neck cancers.
AB  - Head and neck cancers are a significant and worsening health problem in the UK.
      In the absence of screening, minimising diagnostic delay after the onset of
      symptoms improves prognosis. Delay, from the patient's initial experience of
      symptoms to the ultimate diagnosis, consists of two elements--the delay prior to
      presenting to a clinician plus that due to the health professional consulted.
      This study aimed to establish the period of delay between recognition of the
      initial tumour symptoms and the formal diagnosis among a sample of patients
      recently diagnosed with head and neck cancer. Using a semistructured
      questionnaire, 133 men and 55 women were interviewed by a research nurse, and the
      results were related to the clinical findings. Tumour size at diagnosis was
      classified according to T1 (22%), T2 (29%), T3 (27%) and T4 (22%). Of the 186
      patients with complete hospital records, 48 (26%) were diagnosed with cancer of
      the lip and oral cavity (CLOC). From the onset of symptoms to the patients'
      initial decision to seek professional advice, the median period was 4 weeks among
      those with CLOC and 3 weeks for those with other head and neck cancers (OHNC).
      The distribution was highly skewed with delays beyond 6 months occurring among 9%
      of the OHNC group, compared with 3% of CLOC. From the onset of symptoms to a
      consultant appointment, the median delay was 8 weeks for OHNC, but 12 weeks for
      CLOC, with delays beyond 6 months of 13% in each group, respectively. First
      symptoms included 'change in voice' (26%), 'pain' (27%), 'lump' or 'growth' (12%)
      as well as dysphagia, 'infection', 'sore throat', 'ulcers' or 'abscess'. No
      significant association was found between the nature of the first symptoms and
      the urgency with which patients interpreted their symptoms, nor was this related
      to diagnostic delay, sex, age or social class. It is concluded that there is
      substantial variation in time to clinical presentation, particularly for OHNC,
      although professional delay for the majority of these cases was minimal. For
      patients with CLOC there was less variation in patient delay, but clinician delay
      was relatively longer.

PMID- 10889617
TI  - Cancer patients' experiences of nurses' behaviour and health promotion
      activities: a critical incident analysis.
AB  - Patients with head and neck cancer report several disease- and health-related
      problems before, during and a long time after completed treatment. Nurses have an
      important role in educating/supporting these patients about/through the disease
      and treatment so that they can attain well-being. This study describes the cancer
      patients' experiences of nurses' behaviour in terms of critical incidents after
      nurses had given them care to promote health. The study had a qualitative,
      descriptive design and the method used was the critical incident technique.
      Twenty-one informants from the Nordic countries diagnosed with head and neck
      cancer were strategically selected. It was explained to the informants what a
      critical incident implies before the interviews took place; this was defined as a
      major event of great importance, an incident, which the informants still
      remember, due to its great importance for the outcome of their health and well
      being. The nurses' behaviour was examined, and critical incidents were involved
      in 208 cases-150 positive and 58 negative ones-the number of incidents varying
      between three and 20 per informant. The nurses' health promotion activities or
      lack of such activities based on the patients' disease, treatment and symptoms,
      consisted of informing and instructing the patients as well as enabling their
      participation. Personal consideration and the nurses' cognisance, knowledge,
      competence, solicitude, demeanour and statements of understanding were found to
      be important. Continuous health promotion nursing interventions were of
      considerable value for the majority of this group of cancer patients. Oncology
      nurses could reconfirm and update the care of head and neck cancer patients by
      including health promotion activities in individual care plans. By more frequent
      use of health promotion models, such as the empowerment model, the nurses could
      identify and focus on those individuals who needed to alter their life-style as
      well as tailor their approach towards these patient by setting goals for well
      being and a healthy life-style.

PMID- 10889618
TI  - Patients' and nurses' assessment of cancer pain.
AB  - The purpose of this study was to examine hospitalised cancer patients' and
      nurses' assessment of patients' cancer pain and to compare them. The data were
      collected from 51 patient-nurse pairs in two hospitals from oncological and
      medical clinics. Each nurse and patient took part in the study no more than once.
      The data were collected with a structured interview and the questionnaire. The
      intensity of pain was measured with a visual analogue scale (VAS) and the Finnish
      version of the McGill Pain Questionnaire (FPQ). The results showed that the
      differences between patients' and nurses' assessments were statistically
      significant for most intensive pain and for acceptable pain. In both cases
      nurses' assessments of the intensity of pain were lower than patients'
      assessments. The nurses identified 40 words in the verbal FPQ that the patients
      used in describing their experiences of pain. The words used most often by
      patients were agonizing, tender, wave-like and radiant. The word that the nurses
      used most often was that of intense. Nurses' knowledge about pain medication in
      general and morphine in particular was clearly associated with the differences
      observed in estimates of the intensity of pain. Nurses with poor knowledge
      underestimated the patients' most intensive experiences of pain. The difference
      was statistically significant.

PMID- 10889619
TI  - Assessing depression in palliative care patients using the visual analogue scale:
      a pilot study.
AB  - It is widely recognised that depression is not detected and therefore not treated
      in patients who are terminally ill. It is difficult to distinguish depression
      from sadness at the end of life and many of the criteria for diagnosing
      depression are not appropriate in the terminally ill patient. There has been
      considerable interest in using screening tools at the time of referral or
      admission to a hospice, but to date none of these have been validated for use in
      palliative care patients. This pilot study of 25 patients admitted to a hospice
      found that a 100-mm linear visual analogue scale (VAS) correlated well with both
      the depression sub scale and total score of the Hospital Anxiety and Depression
      Scale (HADS) and was found to be quick and easy to complete by most patients. The
      finding suggest that the VAS may be useful as a screening tool for depression in
      patients with advanced metastatic disease and that larger studies comparing VAS
      to clinical psychiatric interviews should be undertaken.

PMID- 10889620
TI  - A qualitative study to explore the experience of fatigue in cancer patients.
AB  - Fatigue--which is a complex, multicausal, and multidimensional subjective
      experience--is today the most frequently reported symptom from patients with
      cancer. The aim of this study was to explore the experience of fatigue in cancer
      patients and to describe the categories and dimensions of the symptoms. A
      qualitative method--grounded theory--was used. Unstructured, tape-recorded
      interviews with 15 cancer patients were used for data collection. The categories
      found in this study illustrate fatigue as a process. Three major categories were
      found: (1) experiences (of loss, need, malaise, psychological stress, emotional
      affection, abnormal weakness, difficulties in taking the initiative); (2)
      consequences (social limitation, affected self-esteem, affected quality of life);
      and (3) actions (coping). The categories were constructed on the basis of
      dimensions with subordinated qualities. Knowledge concerning the different
      expressions of fatigue is important in caring for patients with cancer. The
      results from this study may contribute to a better understanding of how a cancer
      patient can experience and express fatigue and how the symptoms may affect the
      patient.

PMID- 10889621
TI  - Dealing with the uncertainty of developing a cancer.
AB  - Based on a personal experience in a genetic counselling consultation, this
      article proposes a personal reflection about the different ways in which
      individuals from high-risk families are living and dealing with the uncertainty
      of one day developing a cancer. The psychological reactions of the individuals
      concerned are described before exploring actual issues of genetic testing--such
      as the reasons for testing--but also technical and familial limits. This paper
      also presents the limits existing in follow-up and prevention for the carriers of
      susceptibility genes and insists on the importance of counselling before genetic
      testing and the necessity of further multidisciplinary research in this field.
      The original text was presented in French during the Eleventh MASCC International
      Symposium on Supportive Care in Cancer, at Nice, in February 1999.

PMID- 10889622
TI  - Relating information needs to the cancer experience: 1. Information as a key
      coping strategy.
AB  - Information-seeking behaviour is a strategy that many people use as a means of
      coping with, and reducing stress, throughout their cancer experience. The
      importance of providing information to people with cancer and many of the
      problems encountered with its provision have been well documented. Individuals
      frequently express dissatisfaction with the information given to them and
      experience difficulty in retaining and processing information. Lack of
      information may well lead to increased problems with anxiety and coping. This
      paper reviews and explores the literature associated with the information needs
      of people with cancer and the use of information as a coping strategy. The review
      forms part of a phenomenological study, conducted to explore the important issues
      for people with cancer that arose out of their cancer experience. Much of the
      literature discusses information-giving from the viewpoint of healthcare
      professionals rather than from the viewpoint of users and concentrates solely on
      information needs relating to the disease and its medical treatment. There is
      scant reference to the need for information on other issues such as available
      financial and community resources, or coping strategies.

PMID- 10889623
TI  - Loss adaptation.

PMID- 10889624
TI  - Cancer in the elderly: the forgotten priority.
AB  - In 1992, the American Oncology Nursing Society produced a state-of-the-art
      document, recognizing the fact that cancer is primarily a disease of ageing and
      addressing the specific needs of elderly cancer patients. As 1993 has been dubbed
      the 'Year of the Elderly', European oncology nurses should also be establishing a
      framework to meet the cancer-specific needs of the elderly.

PMID- 10889625
TI  - Post-basic cancer nursing education in Belgium: an innovative collaboration
      between a nursing school, a comprehensive cancer centre and the Oncology Nursing
      Society.
AB  - Since 1989, the Nursing School attached to the Free University, Brussels, has
      organized post-basic courses in cancer nursing, with the collaboration of the
      Belgian Oncology Nursing Society (French speaking) (SIO) and a comprehensive
      cancer centre, the Jules Bordet Institute. The 1-day-a-week course evolves over
      30 weeks and is open to registered nurses. Its structure and its content respect
      the recommendations of the Core Curriculum for a Post-Basic Course in Cancer
      Nursing (EONS, 1989). However, there are some differences related to the entry
      requirements, the clinical experience, and the evaluation of both the course and
      the students' performance. So far, 72 nurses from different cancer units from the
      southern part of Belgium have obtained the certificate at the end of this course.
      In parallel with the 1-day-a-week course, seven modular courses were set up
      during the first semester of 1992, with the financial support of the 'Europe
      against Cancer' Programme. Each module tackles a specific theme: Basic Principles
      in Oncology Nursing; Training the Trainers; Prevention and Early Screening;
      Rehabilitation--Palliative Care--Psycho-oncology (one short and one long module);
      Radiotherapy; and Chemotherapy.

PMID- 10889626
TI  - Building a framework for nursing research in cancer care.
AB  - This paper describes a framework for nursing research in cancer care, developed
      by a group of British nurses who met under the auspices of the Cancer Research
      Campaign, a British charity, in May 1992. In developing the framework the great
      potential for nursing research to contribute to cancer care was recognized, but
      was felt to be under-exploited because of the constraints that exist for nurses
      wishing to undertake research. The framework identifies the characteristic
      features of nursing research; highlights key areas for focus for such research;
      suggests mechanisms for building programmes of research; and strategies for
      creating milieux conducive to the development of cancer nursing research and
      nurse researchers.

PMID- 10889627
TI  - Constraints for nursing in developing a framework for cancer care research.
AB  - Oncology nursing has become an important and popular specialist area of care.
      Evidence indicates that there is a disappointingly low level of funded research.
      This paper seeks to identify some of the key constraints which have inhibited the
      development of cancer nursing research. It is proposed that there are two
      priorities to promoting research. First, there is a need to produce the next
      generation of research trained cancer nurses. Secondly, the need for a
      coordinated programme of basic and applied cancer nursing research. This paper
      discusses the difficulties of obtaining research funding and adequate supervision
      for higher degrees. In addition, key constraints in clinical nursing and nurse
      education are identified. In conclusion, it is proposed that there is an urgent
      need for specific cancer-care research funded studentships and the establishment
      of a coordinated programme of research.

PMID- 10889628
TI  - Appetite and appetite stimulants.
AB  - Poor appetite is a common symptom among cancer patients. It can lead to
      inadequate food intake, weight loss, physical debilitation and reduced tolerance
      to anti-neoplastic treatment. Although cancer-induced anorexia is not fully
      understood, there are some theories relating to its development. Interventions
      may be aimed at improving nutritional intake to prevent excessive weight loss
      when poor appetite exists, or it may concentrate on improving appetite by
      pharmacological means. Appetite should be considered alongside other aspects of
      symptom control and tackled aggressively when it is contributing to a poor
      quality of life.

PMID- 10889629
TI  - Patients' perceptions of breast-cancer-related lymphoedema.
AB  - This article describes a study which was designed to explore patients'
      perceptions of breast-cancer-related arm lymphoedema and the factors that may be
      associated with these perceptions. The findings of the study suggest that
      lymphoedema is a unique and complex experience for the patient which influences
      many spheres of life. Adjustment to the condition is impeded by higher limb
      volume and facilitated by appropriate treatment to reduce limb volume.

PMID- 10889630
TI  - A study of the role of the rehabilitation team.
AB  - The aim of this study has been to explore the concept of rehabilitation as a team
      activity in the oncology setting. The researcher has interviewed 15 members of
      the rehabilitation team in a specialist oncology rehabilitation centre in the
      United Kingdom and observed the day-to-day activity in the centre. The grounded
      theory approach has been taken to data collection and analysis. Interviews were
      semistructured and tape-recorded, observations were recorded in the form of field
      notes; these and the tapes were used as working documents in the development of
      theory and transcribed for full analysis. Theories of team work and
      rehabilitation were developed, and subjected to further scrutiny and confirmation
      by participants. Staff recognized the existence of a team and sub-teams, which
      interacted in networks of care, communication and patient referral. Teams were
      seen as fluid, with merging and changing borders. Specialists remained
      individuals within the teams. The essence of rehabilitation was seen as the
      facilitation of the patient to become self-caring and to attain an optimal
      quality of life.

PMID- 10889631
TI  - The implementation of the EC post-basic curriculum in cancer nursing in Greece.

PMID- 10889632
TI  - The development of a European common core educational programme for therapeutic
      radiographers/technicians/nurses.

PMID- 10889633
TI  - Health promotion behaviors of Jordanian women.
AB  - Many developing countries are undergoing industrialization and modernization,
      which has produced both positive and negative implications for health. This study
      was designed to adapt a well-known health measure to an Arab-Muslim population
      and to derive health promotion data for primary health care program planning for
      women in Jordan. A convenience sample of 512 literate females in Jordan was
      recruited from community settings such as secondary schools (teachers), primary
      health care centers (nursing staff and patients), universities (faculty and
      staff), colleges, and office worksites using an Arabic translated version of the
      Health Promoting Lifestyle Profile (HPLP) instrument. Subjects scored highest on
      self-actualization, interpersonal support, and nutrition but scored lower on the
      exercise and health responsibility domains. Unmarried women, however, scored
      higher on exercise and stress management. These findings support the development
      of educational efforts to increase women's awareness of relationships between
      lifestyle and health for both themselves and for their families.

PMID- 10889634
TI  - Coping with the stress of premature labor.
AB  - Premature birth, the leading cause of perinatal morbidity and mortality in the
      United States affects between 8% and 12% of all live births. Approximately 80% of
      premature births are proceeded by premature labor. Significant progress has been
      made in the physical treatment of premature labor; however, the psychological
      cost to women being treated needs further study. My purpose in conducting this
      study was to assess the stress experienced by women treated at home for premature
      labor and to examine methods used by the women to cope. The theoretical framework
      was provided by Lazarus's model of Stress, Coping, and Emotion. A total of 50
      women participated. Twenty responded to a questionnaire that included the
      Perceived Stress Scale (PSS) and the Ways of Coping Questionnaire only, 10 were
      interviewed only, and 20 completed the questionnaire and the interview. RESULTS:
      The women reported experiencing a moderate amount of stress. Their mean stress
      score was 26.75, just below the mean for the instrument (M = 28) and slightly
      less than the stress score of 27.52 reported by women experiencing a "normal"
      pregnancy. Appraisal was assessed by analyzing the data from the interviews. The
      women appraised their situation as both threatening and challenging. They
      described their emotional response most frequently as frustration because of fear
      concerning the pregnancy outcome, loss of control over their life, and inability
      to perform their usual roles of mother, wife, and worker. The women reported on
      the Ways of Coping Questionnaire that they used strategies from three subscales
      to cope with the premature labor. Those subscales were Seeking Social Support,
      Planful Problem-Solving, and Positive Reappraisal.

PMID- 10889635
TI  - Health care participation of perinatal women with HIV: what helps and what gets
      in the way?
AB  - Dealing with the reality of the human immunodeficiency virus (HIV) is a life
      changing challenge to perinatal women as they try to care for themselves and
      their children in environments that often include stigma, uncertainty, and
      limited access to information and health care. Our purpose for this interpretive
      hermeneutic study was to identify factors that women with HIV saw as helping or
      impeding their participation in their health care. We analyzed the qualitative
      data from open-ended interviews conducted with 18 women. We identified the
      facilitating themes of "Staying Healthy for Kids," "God Has His Reasons," and "My
      Family's There for Me." Barriers were "It Hurts to Know," "Health Care System
      Struggles," and "Kids and Buses and Taxies." We found that the women identified
      "Health Care Providers' Behaviors" as both an enhancing and an impeding factor to
      their health care participation. These findings can guide providers to offer more
      "user-friendly" support systems for women with HIV and their children.

PMID- 10889636
TI  - Perceived HIV-related sexual risks and prevention practices of African American
      women in the southeastern United States.
AB  - African American women in the southeastern United States constitute the fastest
      growing segment of those infected with the human immunodeficiency virus (HIV).
      Little data exist about the relationships between HIV infection risks and
      preventive practices. In this article, we describe a focus group investigation of
      how HIV-related sexual risks are perceived by 19 heterosexual African American
      women, ages 18 to 44. Data were analyzed and interpreted using content analysis,
      where key ideas, words, and phrases were grouped based on their relation to the
      purpose of the study. Four themes were revealed: "a man will be a man,"
      inconsistent and/or no condom use, safe relationships, and racism and
      discrimination. Perceived safety within relationships mediated both perceptions
      of HIV-related risks and sexual practices. In light of beliefs about the
      riskiness of sex with high-risk partners, fear of HIV, and the importance of self
      love in minimizing HIV infection risks, the women continued to practice unsafe
      sexual behaviors. Results indicate that women perceive themselves as victims in
      society and that this perception limits their propensity to take action to
      protect themselves from HIV. Successful HIV infection prevention interventions
      need to address negative social and economic factors that define the context of
      many women's lives.

PMID- 10889637
TI  - The Nuer Nutrition Education Program: breaking down cultural barriers.
AB  - Very little is known about the Nuer culture, partly because of its widely
      misunderstood language and because of the mixture of its people with the other
      tribes in Africa, according to Evans-Pritchard). However, it is known that the
      Nuer women's roles in the family seem to be centered around cooking duties. In
      the Nuer culture, no work is considered degrading, and the women know and accept
      their domestic duties. During the summer of 1996, a pilot project was conducted
      as an attempt to help Nuer refugee women of Des Moines, Iowa, incorporate
      nutritional concepts and American food preparation techniques into their existing
      methods of food preparation. The barriers faced involved the Nuer women's
      unfamiliarity with American foods and household items and their inability to read
      and understand English. Cultural issues and barriers were overcome when the
      health educator was willing to take the time to gain the trust and respect of the
      Nuer people. Structured interviews indicated an increase in knowledge of American
      foods and cooking skills. This education program in no way meant to replace
      traditional Nuer cooking methods; rather, it acted as a way to adjust to life in
      the United States.

PMID- 10889638
TI  - The lived experience of Korean immigrant women acculturating into the United
      States.
AB  - Immigration to a different country and a new way of life affects immigrants in
      many different ways. The changes that occur can influence the way they live and
      think as well as their personal health. This is especially true with Korean
      women. However, we still do not have sufficient knowledge about how these women
      adjust to their new environments. The rate of Korean immigration to the United
      States has gradually increased since 1965. According to Bouvier and Arnold, the
      Korean immigrant population is estimated to reach 1.3 million in the year 2000.
      Korea ranks fourth in number of emigrants, closely following the Philippines,
      China, and Vietnam. Research reveals that approximately 45% of recent emigrants
      are women, and this percentage is rapidly increasing. Research concerning this
      population's lives, their process of acculturation, and, above all, their health
      and well-being is lacking greatly in quantity and quality. This study
      demonstrates that the change of women's roles, due to their process of
      acculturation, cannot be considered separate from their well-being. For this
      study, 6 Korean women immigrants living in New York were chosen to provide
      information. The participants volunteered under the condition that their privacy
      and confidentiality would be protected. A pattern of acculturation experience was
      revealed in four successive, principal stages: dreams, conflicts, renunciation,
      and remorse. Hopefully, the following descriptive data will provide knowledge for
      implementing qualitative care requirements for Korean women immigrants in the
      United States.

PMID- 10889639
TI  - Hormone replacement therapy and Alzheimer's disease: an update on the issues.
AB  - Alzheimer's disease (AD) is a significant personal, family, social, and public
      health problem. Currently there is no way to prevent or cure AD. The latest
      opinions on the possibility of hormone replacement therapy (HRT)/estrogen
      replacement therapy (ERT) as a means to prevent and treat AD are reviewed.
      Although prevention and treatment of AD cannot yet be added to the list of
      HRT/ERT's benefits, research in the area is promising. The potential benefits and
      problems of HRT for the woman with or at risk for AD are examined. The potential
      benefits include improved interest and compliance with HRT, improved quality of
      life, and cost savings. The problems include difficulties in monitoring and
      managing clients with AD, assuring compliance with the therapeutic regimen, and
      deciding when to withdraw therapy. Clinical trials have not yet been able to
      determine the appropriate dosages, to standardize or predict the magnitude of the
      therapeutic effect, or to determine the safety of ERT/HRT as a long-term therapy,
      particularly when continued in the elderly years. Implications for practitioners
      are addressed.

PMID- 10889640
TI  - Jackie Nichols.

PMID- 10889641
TI  - ANA 2000: make our house your home.

PMID- 10889642
TI  - Needlestick legislation bill requires safer needle devices.

PMID- 10889643
TI  - Volunteering 101: a short course for the nurse philanthropist.

PMID- 10889644
TI  - Turning tragedy into advocacy. A mother's story.

PMID- 10889645
TI  - Transcultural nursing: an imperative for nursing practice.

PMID- 10889646
TI  - Cultural competence for the Latino population.

PMID- 10889647
TI  - Culturally competent care for traditional Appalachians.

PMID- 10889648
TI  - A calm in the storm. Using visualization to create a sense of peace.

PMID- 10889649
TI  - The ABPN surf is up!

PMID- 10889650
TI  - Conceptualisation of diarrhoea in Nepal.
AB  - Nepal has a small and isolated population, but one which has received
      considerable aid in relation to health. Infant mortality rates are high. One of
      the main causes of infant death is diarrhoeal disease. Mothers can distinguish
      different types of diarrhoea and effect different treatments.

PMID- 10889651
TI  - Nut allergy: symptom and severity reporting.
AB  - Nut allergy, in particular peanut allergy, is becoming more common in children.
      Immune sensitisation to nuts appears to be occurring earlier in life. High
      incidence of other allergic diseases in children with nut allergy. Onset of
      anaphylactic symptoms is quick but symptoms last for a short time. Necessity for
      hospital admission due to severity of allergic reaction is low.

PMID- 10889652
TI  - Preceptorship: the progression from student to staff nurse.
AB  - Preceptorship assists the development from learner to accountable staff nurse.
      Time has to be available for preceptorship to be successful. The learning
      objectives need to be relevant for the individual preceptee. Preceptors require
      considerable support for their role. Preceptees had difficulty adjusting to being
      staff nurses and experienced high levels of stress. Most progress was observed
      after a three month period, when ability and confidence levels had increased and
      stress levels decreased.

PMID- 10889653
TI  - Pain management: a nursing priority?
AB  - Literature suggests that nurses do not prioritize pain management. This study
      aimed to determine the importance paediatric nurses give to pain management and
      whether they report a need for further training. Paediatric nurses completed a
      training needs analysis questionnaire. Analysis demonstrates that nurses do not
      give pain management as high a priority as many of the other aspects of their
      role. Educational deficits about some areas of pain management were identified.
      Educational provision about pain needs re-evaluating at both the pre- and post
      registration level.

PMID- 10889654
TI  - Substance use: whose problem is it?
AB  - Research evidence demonstrates that more young people in the UK are using illegal
      substances. Every child health professional has a central role to play in the
      area of substance use. The HAS Report (1996) advocates a 4 tiered approach
      identifying primary health care staff to providing services for adolescents who
      use substances. Assessment of a young person's health needs is crucial. Nurses
      are ideally placed to have an impact of health issues affecting young people and
      substance use cannot be ignored or treated separately. Child health professionals
      are ideally placed to provide meaningful education and information to young
      people at risk.

PMID- 10889655
TI  - FAS/FAE: impact on children.
AB  - Alcohol is a teratogen and it can cause lasting birth defects called Fetal
      Alcohol Syndrome (FAS)/Fetal Alcohol Effects (FAE). FAS is one of the leading
      causes of mental retardation. FAS/FAE can result in a myriad of behavioral,
      learning and developmental problems. There are estimates of 12,000 new cases of
      FAS yearly. The school nurse plays an important advocacy and educational role in
      helping the child with FAS. Family involvement is important for the child with
      FAS.

PMID- 10889656
TI  - The acquisition of speech and language.
AB  - There are many theories behind speech and language acquisition. The role of
      parents in social interaction with their infant to facilitate speech and language
      acquisition is of paramount importance. Several pathological influences may
      hinder speech and language acquisition. Children's nurses need knowledge and
      understanding of how speech and language are acquired.

PMID- 10889657
TI  - Every child deserves a perfect childhood.

PMID- 10889658
TI  - Post-renal transplant compliance.
AB  - A selective review was undertaken to identify factors which may affect a child's
      compliance with immunosuppressive therapies, post-renal transplant. Studies were
      categorised as either examining compliance from an experiential or selective
      attribution approach. There are multiple reasons for non-compliance. Children and
      families require much more support than previously recognised.

PMID- 10889659
TI  - Urinary tract infection in babies and pre-school children.

PMID- 10889660
TI  - Nursing the preterm surgical neonate.
AB  - The preterm neonate's response to surgery manifests in all body systems.
      Necrotising Enterocolitis (NEC) is an acute gastro-intestinal emergency requiring
      surgical intervention. Severe NEC may require the removal of infarcted bowel.
      Examining the response to surgery in the preterm neonate with NEC offers nurses a
      rationale for their post-operative care. Both physiological and psychological
      responses need to be understood in the light of family centred care.

PMID- 10889661
TI  - Clinical competency: the right assessment tools?
AB  - Effective assessment of competency of student nurses in clinical practice is
      vital. Use of simulation rather than real life settings can be used to assess
      competency. Development of information technology and its use in teaching
      clinical skills offers opportunities for assessment. Clinical governance
      increases the need to scrutinize the assessment of practice. Ongoing assessment
      of clinical competency for qualified nurses is also important.

PMID- 10889662
TI  - Maternal identity in preterm birth.
AB  - The development of maternal identity appears to be considerably delayed in the
      event of preterm birth. Women with high risk pregnancies may be afforded some
      protection by means of adaptation prior to birth. Tactile contact appears to make
      the experience more real for women who are attempting to make the transition to
      motherhood. Even in a group of moderate risk preterm infants, the psychological
      challenges facing mothers experiencing neonatal intensive care are considerable.
      Conflicting responsibilities and time pressures contribute significantly to the
      stressful experience of mothers in NICU.

PMID- 10889663
TI  - Clinical supervision: users' perspectives.
AB  - The clinical supervision relationship is valuable for the development of good
      practice. The necessary ingredients of clinical supervision are safety,
      impartiality, support, trust and respect. Reflection of thoughts, feelings and
      actions allows debriefing, challenge and understanding. The perceived outcomes of
      clinical supervision are personal, professional and clinical skills development.
      Aligning clinical supervision with PREP may provide motivation for Nurses and
      Trusts.

PMID- 10889664
TI  - A tripartite approach to assessing practice.
AB  - Assessment of clinical practice is at least as important as assessment of theory.
      To date the assessment of clinical competence at differing levels has been
      neglected. When assessing clinical practice it is vital to utilise multiple
      sources of evidence. A tripartite relationship of practitioner or student,
      supervising practitioner, and lecturer is a versatile arrangement for evaluating
      evidence of achievement.

PMID- 10889665
TI  - Envisioning health care using a StoryTech process with continuing education
      participants.
AB  - BACKGROUND: Participants representing rural and regional health care providers,
      employees, and consumers were involved in a continuing education (CE) conference
      focused on envisioning tomorrow's health. The 1993 attendees were taught a
      process of envisioning health care 5 years into the future. The 1993 projected
      outcomes were reviewed with 1998 realities. METHOD: Continuing education
      participants (N = 417) generated their design for a healthy future by responding
      to six story scenarios. Stories (2,502) related to quality of health care were
      analyzed in a three-step process. RESULTS: Findings from the concept analysis of
      stories obtained at the 1993 CE conference revealed a conceptual model for a
      desired health future for 1998, with four major concepts, five goals, and five
      guiding principles. CONCLUSIONS: Visioning in a CE environment creates valuable
      direction for an improved health care future. A CE conference provides the seeds
      and opportunities for dialogue and partnership by people responsible for
      implementing action plans that potentially would create a healthy community.

PMID- 10889666
TI  - Competency-based education: maximize the performance of your unlicensed assistive
      personnel.
AB  - BACKGROUND: Providing patient care by using the most cost effective means has
      compelled skill mix changes in many hospitals. The need for educational programs
      are crucial to prepare unlicensed assistive personnel (UAP) for their new roles.
      METHOD: Using a competency-based approach, an educational program was designed to
      develop specific technical skills to target complex competencies and to improve
      the participants' knowledge and skill performance. The educational program met
      the five program objectives. RESULTS: Unlicensed assistive personnel gained
      knowledge and competency in new skills, as assessed in the education program and
      when applied in the clinical units. The most important outcome was the
      participants' expressed eagerness to learn more and their desire to work as
      contributing members of the health care team. CONCLUSION: The educational program
      adequately trained UAP and created a foundation of relationships and teamwork
      that enhanced the patient care delivery with cost efficiency.

PMID- 10889667
TI  - Transcultural reflection on clinical teaching using an experiential teaching
      learning model.
AB  - BACKGROUND: A 6-day professional development workshop was designed and
      implemented in China as part of a project funded by the Canadian International
      Development Association through the Canada-China University linkage program.
      METHOD: Kolb's experiential learning model was used as a framework to help
      Chinese nurse educators reflect on their practice as clinical teachers. RESULTS:
      The workshop resulted in the generation of new insights by participants into
      their role as clinical teachers. Chinese educators wanted to increase their links
      between the teaching of theory at the college and the instruction of students in
      the practice setting. CONCLUSION: The use of a similar approach in future
      professional development workshops allows presenters to identify nurses' learning
      needs regarding specific areas of nursing practice and education.

PMID- 10889668
TI  - The integration of research by nurse educators: advancing practice through
      professional development programs.
AB  - BACKGROUND: This article describes how nurse educators at The Hospital for Sick
      Children, Toronto, have used Benner's findings as a framework to direct the
      advancement of professional development programs, specifically preceptorship,
      orientation, and central education programs. METHOD: Narrative methodology was
      introduced as a key educational strategy to capture the complexity of pediatric
      clinical practice and enhance learning experiences. RESULTS: The shift in content
      and structure of the education programs from a structured behavioral teaching
      learning framework to the use of narrative methodology has enhanced learning,
      professional development and clinical practice. CONCLUSION: Participant
      evaluations of these programs suggest a high level of satisfaction with the use
      of narrative methodology. Evaluative measures focusing on the relationship
      between narrative methodology, professional development, and client outcomes is
      needed. This evaluative approach that measures outcomes is imperative to future
      directions in program planning.

PMID- 10889669
TI  - Computer conferencing in graduate nursing education: perceptions of students and
      faculty.
AB  - The authors report the perceptions of students and faculty who participated in a
      computer conferenced (CC) graduate course in nursing. Ten graduate students and
      three faculty members completed a course evaluation form, which included items
      about learning, interaction, environment, technical support, and satisfaction
      with CC. Responses indicated the CC medium offered a creative and flexible
      alternative for learning. Course participants perceived benefits such as enriched
      learning, meaningful interactions, opportunities for reflection, satisfaction
      with the technology, and the convenience of learning from a distance. These
      results have implications for facilitating continuing education.

PMID- 10889670
TI  - Using facilitators in mock codes: recasting the parts for success.
AB  - BACKGROUND: Members of the CHRISTUS Santa Rosa Children's Hospital staff
      development committee identified a need for a mock code program which would
      address a range of learning needs for nurses and other caregivers with varying
      levels of knowledge, skills, and experience. METHOD: We implemented a mock code
      program using experienced caregivers, usually emergency room and pediatric
      intensive care RNs and respiratory therapists to serve as facilitators to code
      participants during the mock code drills. Facilitators have dual roles of
      teaching and guiding the code participant as well as evaluating performance.
      RESULTS: Code participants and facilitators benefit from the design of this
      program. Debriefing session input and written program evaluations show that code
      participants value the opportunity to practice their skills in a nonthreatening
      situation in which they receive immediate feedback as needed. Facilitators learn
      to teach and coach and strengthen their own code knowledge and skills at the same
      time. CONCLUSION: This mock code program serves as a unique way to include novice
      and experienced nurses in mock codes together. The knowledge, skills, and
      confidence of the code participants and the facilitators have matured. The design
      of the program allows for immediate teaching/learning where needed, as well as
      appropriate evaluation. This program develops stronger, calmer, more efficient,
      and more confident nurses during codes. Practice and equipment changes can be
      based on findings from the mock codes. The program is invaluable to patients,
      staff, and hospital.

PMID- 10889671
TI  - Thoughts about the millennium: the importance of children and parenting.

PMID- 10889672
TI  - Identification and management of urinary tract infection in the preschool child.
AB  - Urinary tract infections commonly occur in preschool children and can be
      associated with significant morbidity if they are not identified quickly and
      treated appropriately. Vesicoureteral reflux is found in a larger proportion of
      these patients. Recognizing and treating risk factors such as dysfunctional
      voiding may aid in the resolution of vesicoureteral reflux and reduce the
      recurrence of urinary tract infections.

PMID- 10889673
TI  - Empowering adolescents with asthma to take control through adaptation.
AB  - Clinical nurse specialists, family nurse practitioners, pediatric nurse
      practitioners, and pediatric nurses in schools, primary practice settings, and
      the emergency department are at the front line of caring for adolescents with
      asthma. By empowering adolescents, these health care professionals can reduce the
      cost of health care and morbidity for these patients. The purposes of this
      article are (a) to discuss adolescence and powerlessness and (b) to identify
      nursing interventions that can empower adolescents to adapt behaviors that will
      enhance the prevention of acute attacks and encourage preventive management of
      the disease process. The article will also discuss current nursing strategies
      used with adolescents to promote feelings of power and control of medications and
      treatment based on current national guidelines and the Roy adaptation model.

PMID- 10889674
TI  - Nursery privileging for pediatric nurse practitioners.
AB  - Developing a nursery privileging policy for pediatric nurse practitioners (PNPs)
      in a hospital that has not previously used PNPs in this capacity requires a clear
      understanding of the issues, a well-thought-out plan, and a win-win approach.
      Current trends in privileging of PNPs are summarized. The credentialing and
      privileging processes are defined, and the relationships that PNPs must establish
      with medical and administrative staff are explored. Five steps PNPs should take
      before requesting nursery privileges along with approaches to managing conflict
      are suggested. A case example involving the creation of a nursery privileging
      policy is included.

PMID- 10889675
TI  - A guide to the pediatric patient with "difficult" asthma.
AB  - Patients whose asthma symptoms are poorly controlled with the therapies usually
      recommended for this disease are considered to have "difficult" asthma. Although
      such patients represent a small proportion of patients with asthma, children who
      have difficult asthma are at increased risk for morbidity and mortality. Once the
      diagnosis of asthma is established, caregivers must appropriately categorize and
      treat the asthma according to the patient's level of symptom severity. The
      purpose of this article is to present an approach to the management of patients
      with difficult asthma by (a) searching for alternative diagnoses or conditions
      that are often associated with asthma, (b) investigating environmental issues,
      (c) reviewing inhalation techniques, and (d) determining the patient's level of
      compliance with the prescribed treatment plan and simplifying it whenever
      possible.

PMID- 10889676
TI  - Pediatric home care: reimbursement and cost benefit analysis.
AB  - Home care has been described as the fastest growing component of personal health
      care spending, and pediatric home care as the fastest growing segment of the home
      care field. Because of the continued progress in pediatric medicine and advances
      in technology, a growing population of children with complex chronic and terminal
      conditions can be cared for at home. A growing subspecialty in pediatric health
      care is delivering services for infants and children with HIV infection or AIDS
      and those born to mothers addicted to drugs or alcohol. This article describes
      the reimbursement and cost-benefit issues surrounding pediatric home health care,
      with particular attention to the HIV/AIDS pediatric population.

PMID- 10889677
TI  - Child's drawing: Steve's family.

PMID- 10889678
TI  - Treatment of neonatal abstinence syndrome.

PMID- 10889679
TI  - Red, edematous toes in two infants.

PMID- 10889680
TI  - Medicare billing numbers: a necessity for PNPs.

PMID- 10889681
TI  - Every ride a safe ride.

PMID- 10889683
TI  - Health promotion: a golden opportunity for school nurses.

PMID- 10889682
TI  - Polio immunization: dealing with new recommendations and helping parents
      understand the changes.
AB  - After remaining unaltered for almost 3 decades, the guidelines for polio
      immunization have recently undergone some major changes. A shift away from use of
      the live oral poliovirus vaccine has occurred, and an increasing preference is
      being shown for the killed injectable poliovirus vaccine for at least the first 2
      doses. The purposes of this article are to review the history of polio and polio
      vaccines; compare the risks, benefits, and indications of the 2 available
      vaccines; discuss the rationale for changes in recommendations; and help nurse
      practitioners guide parents in making decisions about vaccines.

PMID- 10889684
TI  - Factors contributing to the overuse of chemical pesticides in children with
      persistent head lice.
AB  - A growing number of head lice cases, for reasons that are not entirely clear, are
      repetitive or enduring. Despite the emerging phenomena, there has been little in
      the literature to guide school nurses in their day-to-day struggle with families
      experiencing head lice infestations that persist despite repeated treatment
      attempts. Children with persistent head lice are at increased risk of
      overexposure to chemical pesticides from multiple-treatment sources. In addition,
      school absences for persistent head lice infestations place children at risk
      educationally.

PMID- 10889685
TI  - Opportunities for pregnant and parenting teenagers: a school-based and school
      linked intervention program.
AB  - Three hundred and ninety (390) pregnant and parenting teens participated in a
      school-based and school-linked federally funded program at 10 high-risk schools.
      The program was designed to (1) increase the use of referred services and
      attendance at these services without students' missing school, (2) increase
      academic skills, and (3) increase health and well-being of the students and their
      infants. The program provided 18 services coordinated at the school or provided
      on site. The end-of-year evaluations indicated 88% to 95% of teens attended
      services that were recommended, and 69% did not miss school to receive these
      services. The teens' rate of passing their grade level increased at the end of
      the program year. Additionally, 78% used birth control, and over 90% of the
      infants received timely health care. The qualitative data provided by students
      indicated pregnant and parenting teens wanted to remain in school despite the
      struggles they encountered. The process evaluation provided by the coordinators
      at each school indicated that communication and cooperation between program staff
      and school nurses were the key elements in enabling teens to receive the targeted
      services.

PMID- 10889687
TI  - Create a virtual community: start an Internet discussion list.
AB  - Internet discussion lists are valuable tools for sharing resources, creating
      professional relationships, and remaining current in a specialty. Despite the
      proliferation of health-related lists, there are still school nurse
      subspecialties and associations that would benefit from professional mailing
      lists. The process of starting a list is simple and quick. The effort required to
      manage a list is well worth the benefits of creating a virtual professional
      school nurse community.

PMID- 10889686
TI  - Assessment of potential inhalant use by students.
AB  - Inhalant use is a significant health risk for today's youth, so school nurses
      need to be aware of its prevalence and life-threatening consequences. Numerous,
      readily available, inexpensive substances are being inhaled by a growing number
      of students. The effects of inhaling such substances can be devastating.

PMID- 10889688
TI  - Creating a living document: developing the National Association of School Nurses
      Mission Statement for the new millennium.
AB  - The second in a series of three articles devoted to the development, maintenance,
      and implementation of the National Association of School Nurses 1998-2001
      Strategic Plan and how it relates to the practice of school nurses. Information
      about the development of a mission/vision statement for the organization is given
      along with strategies for developing a local school district school health
      program strategic plan. A previous Nursing Practice Management section article
      discussed the development of the Association's strategic plan considering the
      changing health care climate, the shifting needs of school children, and the
      economic climate for school funding. A future Nursing Practice Management section
      article will discuss the implementation of the seven goal areas in the National
      Association of School Nurses 1998-2001 Strategic Plan.

PMID- 10889689
TI  - Introducing a new section--legal and ethical issues.

PMID- 10889690
TI  - A successful strategy. Garnering community support for contraceptives services to
      be provided in a school-based health center.
AB  - The original planning group for a school-based health center sensed controversy
      in the community over the provision of contraceptive services at the high school.
      They initially made the decision to exclude contraceptive services; however, the
      planning group provided a stipulation in their package that an assessment of the
      community regarding contraceptive services be conducted after the clinic had been
      open for one year. This article describes the strategies and activities of the
      clinic staff at the one-year point to assess community values and support
      comprehensive services to adolescent students. We began with fact gathering, then
      planned a parent survey and faculty survey, followed by faculty focus groups,
      meetings with clergy and a second survey that included all parents in the school,
      as well as parents of incoming students. Community forums were held to obtain
      feedback and provide information. Our efforts culminated in a school board vote
      of six to one to allow us to provide contraceptive services.

PMID- 10889691
TI  - Immunization rates: a community assessment approach for diagnosis.
AB  - Concerned about low immunization rates, school nurses, nursing school faculty,
      and public health nursing graduate students formed a partnership to identify the
      problems underlying the low rate of immunizations. Utilizing a representative
      school district within a large metropolitan area, the process was expedited by an
      assessment of the community, including a windshield survey, resource survey,
      collection of demographic data, and generation of mapping software to highlight
      relationships within census tracts. These relationships emphasized immunization
      rates within census tracts by concentrations of single-parent families,
      residential mobility, or foreign nationality. In addition, interviews were held
      with key informants in the community and with parents. In this instance,
      communication with the parents was a critical factor in determining that the
      problems were neither access issues nor parental lack of concern but instead
      communication problems. A simplified communication strategy to parents that is
      well timed can be a low-cost solution to the concern over low immunization rates.

PMID- 10889692
TI  - Ethics in transplantation: perspectives for the next millennium.

PMID- 10889693
TI  - The "noncompliant" transplant patient: a persistent ethical dilemma.
AB  - The term noncompliant patient may evoke the image of a difficult, demanding, and
      troublesome patient. In the transplant environment, patients who are unable or
      unwilling to adhere to a prescribed plan of treatment raise a number of medical,
      ethical, and other concerns with respect to individual patient care. Their
      behavior also raises questions of justice and fairness, especially in light of
      the limited numbers of transplantable organs available and the very large number
      of people who are waiting for a transplant. Patients who are unable to do what is
      necessary to maintain a transplanted organ may create a moral dilemma for the
      healthcare providers who treat them. This article will (1) attempt to develop a
      more complete understanding of "patient noncompliance," (2) address concerns that
      arise both before and after the transplant, and (3) suggest strategies for
      dealing with noncompliant patients.

PMID- 10889694
TI  - Ethical assessments of brain death and organ procurement policies: a survey of
      transplant personnel in the United States.
AB  - The Questionnaire on Prolonging and Shortening Life was developed to assess the
      views of medical personnel regarding brain death, organ procurement policies, and
      related issues. The questionnaire was completed by 189 transplant physicians, 197
      clinical coordinators, 150 medical students, and 70 nursing students. Ninety-five
      percent supported the so-called dead donor rule. What this rule means in practice
      appeared unclear among the population. More than 60% supported procuring organs
      from anencephalic and "higher brain-dead" patients, although patients in both
      groups are not dead by current legal standards. Performance on items relating to
      so-called non-heart-beating organ donation suggested that 75% of the group do not
      support non-heart-beating organ donation without assurance that the donors are
      brain-dead before procurement begins. Given that current recommendations to
      increase organ donation look to non-heart-beating organ donation rather than to
      anencephalic patients and those in a persistent vegetative state, these findings
      suggest that further ethical discussion and analysis are urgently needed.

PMID- 10889695
TI  - Clinical decision making and ethics in communications between donor families and
      recipients: how much should they know?
AB  - Advances in organ recovery and transplantation have provided us with the skills
      and opportunity to save, extend, and improve the quality of life for many. But
      with these opportunities have come challenges to redefine our practice and
      relationships with donor and recipient families. Although most donor families and
      transplant recipients receive some information about each other, many still do
      not. In the past, communication between donor families and recipients has been
      anonymous and highly controlled, with much inconsistency among and within the
      transplant community, leaving many involved in the process confused and
      frustrated. Transplant professionals may wish to consider critically the common
      ethical values of autonomy, beneficence, salience and benefit of choice in making
      decisions about information shared with and contact between donor families and
      recipients.

PMID- 10889696
TI  - Ethical dilemmas in living donor organ transplantation.
AB  - Living related donors are an increasing source of organs for transplantation.
      Although the use of this type of donation is widespread in the United States, the
      practice of placing donors at risk for injury or illness without physical benefit
      can create ethical dilemmas for health professionals dedicated to healing and
      avoiding harm. It is important for transplantation professionals to be familiar
      with the risks and benefits associated with living donation within their own
      specialty area. Placing living donation within an ethical framework can allow for
      careful consideration and guide decision making in each individual case. Drawing
      upon the literature for examples from several of the transplantation specialty
      areas, this article reviews some of the risks and benefits associated with living
      donation and identifies the limits of the utilitarian and casuistic ethical
      framework in guiding decision making in living donation. An ethical framework of
      virtue-principlism is offered as one which is grounded in an understanding of
      what it is to be human and in the nature of the health professional-patient
      relationship.

PMID- 10889697
TI  - Ethical analysis of organ recovery denials by medical examiners, coroners, and
      justices of the peace.
AB  - CONTEXT: Despite its pivotal nature, until the early 1990s the role of medical
      examiners, coroners, and justices of the peace was largely ignored in discussions
      of the critical shortage of organs for transplantation in the United States.
      These officials have the right to determine, from a medico-legal perspective,
      whether a deceased person can be an organ donor. Thus, they play an important
      role in the donation process. Using a principles-based ethical framework, this
      article examines the problem of nonrecovery of life-saving organs for
      transplantation in the United States because a medical examiner or other official
      denies recovery. OBJECTIVE: The goals of organ donation and the collection of
      forensic evidence are not mutually exclusive. An analysis of the ethical
      principles and obligations of beneficence, respect for autonomy, and justice
      reveals that medical examiners and other officials could probably, after
      appropriate review, release all cases under their jurisdiction for organ
      donation. CONCLUSION: Medical examiners, coroners, and justices of the peace
      could assume a leadership role, working together on public policy with medical,
      social, and legal groups, spearheading efforts to stop the loss of organs due to
      official denials, up to and including state and federal regulation and
      legislation. Beyond their professional obligations, as agents of a social
      institution, medical examiners and other officials have the more general ethical
      responsibility of promoting the public health and welfare and of reinforcing
      societal consensus that transplantation is a social good which should be
      optimized through formal and informal activities.

PMID- 10889698
TI  - Financial incentives: alternatives to the altruistic model of organ donation.
AB  - Improvements in transplantation techniques have resulted in a demand for
      transplantable organs that far outpaces supply. Present efforts to secure organs
      use an altruistic system designed to appeal to a public that will donate organs
      because they are needed. Efforts to secure organs under this system have not been
      as successful as hoped. Many refinements to the altruistic model have been or are
      currently being proposed, such as "required request," "mandated choice," "routine
      notification," and "presumed consent." Recent calls for market approaches to
      organ procurement reflect growing doubts about the efficacy of these refinements.
      Market approaches generally use a "futures market," with benefits payable either
      periodically or when or if organs are procured. Lump-sum arrangements could
      include donations to surviving family or contributions to charities or to funeral
      costs. Possibilities for a periodic system of payments include reduced premiums
      for health or life insurance, or a reciprocity system whereby individuals who
      periodically reaffirm their willingness to donate are given preference if they
      require a transplant. Market approaches do raise serious ethical issues,
      including potential exploitation of the poor. Such approaches may also be
      effectively proscribed by the 1984 National Organ Transplant Act.

PMID- 10889699
TI  - Xenotransplantation.
AB  - Xenotransplantation is a potentially promising but exceedingly complex issue. It
      is critical that this subject be discussed within and outside the transplant
      community. The need for an expanded organ supply is urgent, but the scientific
      and ethical positions are complex. This article reviews the current status of
      xenotransplantation, including the potential benefits and risks; discusses
      multiple ethical issues; and makes recommendations for the transplant
      coordinator.

PMID- 10889700
TI  - Ethical challenges in infant heart transplantation: a clinical case presentation.
AB  - Although heart transplantation has become recognized as a viable option for the
      treatment of incorrectable heart disease in infants and children, its application
      becomes less clear in infants with potentially serious neurologic impairment. The
      following case study illustrates one transplant team's approach to decision
      making in the case of an infant born with a chromosomal deletion syndrome.

PMID- 10889701
TI  - No simple answers: ethical conflicts in pediatric heart transplantation.
AB  - Ethical issues in pediatric heart transplantation are encountered daily in the
      work of the transplant coordinator. Issues such as use of resources in a just
      world, less-than-ideal candidates, and informed consent are challenges to the
      transplant professional. This article explores those issues using the language of
      ethics to analyze the conflicts they present. Resolutions will not necessarily be
      offered, as there are no simple answers.

PMID- 10889702
TI  - Ethics resources of US organ procurement organizations and transplant centers.
AB  - The medical disciplines of organ and tissue donation and transplantation present
      many life-enriching benefits but are often fraught with ethical ramifications.
      This article examines the current and potential ethics resources of US organ
      procurement organizations (OPOs) and transplant centers (TCs). The organizations
      were surveyed regarding established ethical guidelines and the frequency with
      which ethical issues in need of resolution were encountered. All OPOs and 76% of
      TCs reported confronting ethical issues in the workplace. A majority of those
      surveyed in TCs and OPOs felt adequately prepared to face the ethical challenges
      of their jobs. More than half the surveyed personnel had some type of ethics
      training, but only 25% of the TC staffs and 16% of the OPO staffs' training was
      during the survey year. The potential for ethics-related interactions for TC and
      OPO staff must be recognized and adequate preparatory measures provided.

PMID- 10889703
TI  - The dilemma of too few hearts.
AB  - The number of patients being listed for heart transplantation continues to
      escalate. Despite a variety of attempts to increase organ donation, the number of
      available donor hearts remains unchanged. This imbalance of supply and demand
      creates medical rationing of donor organs. When the success of heart
      transplantation became apparent, selection criteria was relaxed, further
      increasing the disparity between the numbers of donor hearts and potential
      recipients. Decreasing the demand by tightening the selection criteria is the
      most reasonable solution at this time.

PMID- 10889704
TI  - Radiopharmaceuticals and their use in the current practice of nuclear medicine.

PMID- 10889705
TI  - Thyroid imaging.
AB  - Four modalities are being used to image the thyroid gland: (1) scintigraphy
      ("scanning"), employing one of several currently available radiopharmaceuticals,
      (2) ultrasound (US), (3) computed tomography (CT, "CAT" scan), and (4) magnetic
      resonance imaging (MRI). The first method, scintigraphy, provides an image of the
      spatial distribution of thyroid functional attributes, the nature of which are
      dependent on the interaction between the particular radiopharmaceutical employed
      and the tissue in question, whereas the latter three modalities provide an image
      of the spatial distribution of structural attributes such as the varying degrees
      of echogenicity of the tissues examined or the differential tissue attenuation of
      an x-ray beam, which permits visualization of the structures. A fifth modality,
      fluorescent thyroid scanning, in which fluorescence of the iodide within the
      thyroid gland is induced by low-dose external radiation and which gives an image
      of iodine distribution, is generally unavailable and only rarely used. For most
      patients, the combination of careful history, skilled physical examination, tests
      of thyroid function (and serum thyroglobulin and calcitonin for cancer
      evaluation), fine needle aspiration biopsy, and scintigraphy provide the most
      cost-effective means of evaluating the thyroid gland and its diseases. Of the
      four modalities currently used to image the thyroid gland--scintigraphy,
      ultrasound, computerized tomography, and magnetic resonance imaging--only
      scintigraphy has the widest application. It is employed to determine gland size,
      locate thyroid tissue, evaluate nodules and masses, determine the cause of a
      painful tender gland, differentiate various forms of goiter, detect
      differentiated thyroid carcinoma and gland remnants, assess suppressibility or
      stimulatability of the gland, and identify nonfunctioning cancers.
      Ultrasonography, computed tomography, and magnetic resonance imaging are not
      useful in differentiating between benign and malignant nodules, and their
      sensitivity in detecting impalpable nodules is not clinically useful, because
      nodules less than 1 to 1.5 cm in diameter are only rarely clinically significant.
      These modalities have limited utility in the evaluation of the thyroid gland:
      they are useful in sizing known lesions and for the detection of cervical
      lymphadenopathy in thyroid cancer cases.

PMID- 10889706
TI  - PET in clinical practice.
AB  - Positron emission tomography (PET) is a nuclear medicine imaging tool that has
      expanded from its vital role in basic research into clinical medicine. This
      noninvasive diagnostic modality is used in cardiac perfusion and viability; in
      neurologic conditions such as epilepsy, dementia, and tumor; and in a wide range
      of common cancers to diagnose, stage, and monitor therapy. The importance of PET
      in clinical practice is growing rapidly, and the number of PET centers across the
      country is increasing. It is imperative, therefore, that physicians are familiar
      with PET, and know where this tool can be the most useful and cost-effective
      modality for patient management.

PMID- 10889707
TI  - Case studies in PET.
AB  - In recent years primary care providers have been increasingly called on to
      broaden their management of patients, particularly in their role as gatekeepers
      to reduce healthcare costs. Obviously a wide spectrum of specialty involvement
      exists, ranging from the classic family practitioner managing all of the common
      diseases and referring challenging cases to specialists, to the internist with a
      background and interest geared toward handling more specialized neurologic,
      cardiac, or oncologic diseases. Whatever the case, primary care providers can
      have a great impact on diagnosis and management of illness by consulting with the
      radiologist about the use of the emerging technology of positron emission
      tomography (PET).

PMID- 10889708
TI  - What is a PET scan?

PMID- 10889709
TI  - Radioactive iodine administration for outpatients.

PMID- 10889710
TI  - A case of mistaken hepatic lesion.

PMID- 10889711
TI  - The power of focus. Who are we?

PMID- 10889712
TI  - The trend toward paralegal training for LNCs--your professional choice.

PMID- 10889713
TI  - Taking a leap of faith.

PMID- 10889714
TI  - Fulfilling your vision of success.

PMID- 10889715
TI  - Almost doesn't count.

PMID- 10889716
TI  - Learning to rise to the challenge.

PMID- 10889717
TI  - Putting myself on the fast track.

PMID- 10889718
TI  - A LNC's first test.

PMID- 10889719
TI  - Setting an ambitious goal.

PMID- 10889720
TI  - Angel voices everywhere.

PMID- 10889721
TI  - Finding a dream job where you least expect it.

PMID- 10889722
TI  - Follow through on your commitment.

PMID- 10889723
TI  - Do something you love.

PMID- 10889724
TI  - The big squeeze.

PMID- 10889725
TI  - Killer in the house.

PMID- 10889726
TI  - Enough is enough.

PMID- 10889727
TI  - Visiting team.

PMID- 10889728
TI  - Undervalued, unashamed.

PMID- 10889729
TI  - Labouring under an illusion.

PMID- 10889730
TI  - The low-down on pay and conditions.

PMID- 10889731
TI  - Do your homework.

PMID- 10889732
TI  - Unit-linked excellence.

PMID- 10889733
TI  - Back to basics continence.

PMID- 10889734
TI  - Morsel things.

PMID- 10889735
TI  - Female catheterisation.

PMID- 10889736
TI  - No such thing as a typical day.

PMID- 10889737
TI  - Heliox in upper airway obstruction.
AB  - The use of a helium-oxygen (heliox) mixture in patients with airway obstruction
      was used as early as the 1930s. Although heliox does not resolve airway
      obstruction, it decreases airway resistance providing time to allow other
      treatments to become therapeutic, and thus, possibly preventing the need for
      intubation and mechanical ventilation. Despite new and advanced treatment options
      in airway obstruction, heliox continues to be a choice for treatment. It is
      important for critical care nurses to understand the rationale for the use of
      heliox, the mechanism of action and administration of heliox. Through a case
      study, the authors discuss the physical properties of helium and its use in
      airway obstruction. Nursing management of patients receiving heliox is also
      reviewed.

PMID- 10889738
TI  - Accuracy of leveling hemodynamic transducer systems.
AB  - Critically ill patients frequently have invasive catheters placed to monitor
      hemodynamic pressures and to calculate hemodynamic indices. Correct leveling to
      the appropriate anatomical structure is critical as the pressure readings guide
      management of fluids, drug administration, and other interventions. The authors
      of this study investigated the accuracy with which registered nurses and
      respiratory technologists were able to level hemodynamic transducers to the
      phlebostatic axis using visual checks, a carpenter's level, and a laser leveling
      device. The results indicate that both groups were unable to accurately level
      transducers with visual checks alone. Use of a leveling tool improved accuracy.
      The laser level was superior for accuracy and speed and preferred for dexterity
      required, ease of use and patient safety. The data supports the need for a tool
      to accurately level hemodynamic transducer systems and suggests that the laser
      leveling device is the tool of choice.

PMID- 10889739
TI  - Holistic care in the critical care setting: application of a concept through
      Watson's and Orem's theories of nursing.
AB  - For the critical care nurse, two concerns increase the complexity of competent
      nursing care. First, the intrusion of technology into the critical care
      environment is more conducive to the use of the medical model than to a nursing
      theoretical framework. Technology has quantified body functions that were once
      elusive to man, enabling practitioners to treat dysfunction and disease.
      Technology, which has provided health care equipment that can maintain breathing,
      circulation and other important quantifiers of life, is welcomed by a society
      that fears finality. Second, the critical care nurse must remain cognizant that
      technology cannot care for the whole being who is in a health care crisis.
      Holistic caring, the being-with, the empathy, the interconnected experience of
      need and response within a nursing theoretical framework is the nurse's art. It
      is this art of caring that is the qualifier of life. It is the balance of
      technological competency with the art of nursing that promotes adaptations in
      health crises. Application of holistic caring through established nursing
      theories such as Watson's theory of nursing and Orem's theory of nursing enable
      the critical care nurse to acquire an expert level of nursing care.

PMID- 10889740
TI  - Innovation fund report: guidelines for withdrawal of life support.

PMID- 10889741
TI  - How to promote physical activity in a community: research experiences from the US
      highlighting different community approaches.
AB  - Much of the research investigating methods for promoting physical activity has
      occurred on an individual or group level of analysis. Yet, the substantial
      prevalence of physical inactivity in most developed countries coupled with the
      public health significance of becoming more regularly active provides a
      compelling rationale for expanding interventions to higher levels of impact. By
      targeting the community, the possibility of reaching a greater percentage of the
      underactive population with potentially lower costs per person becomes more
      likely. When the target of intervention becomes the community, as opposed to the
      individual, a shift in the methods by which the physical inactivity problem is
      both conceptualized and addressed is required. Successful intervention strategies
      that have occurred at each level of impact (i.e. personal/interpersonal,
      institutional, environmental, legislative/policy-level) are highlighted.
      Suggested future directions are summarized.

PMID- 10889742
TI  - How to promote physical activity through individual counseling--a proposal for a
      practical model of counseling on health-related physical activity.
AB  - A model was developed to aid practical decision making in the counseling of
      health-related physical activity. The development was based on the following
      concepts and theories: (1) A wide concept of physical activity; (2) A logical
      sequence of the practitioner's work steps; (3) Personal aspect of the client; (4)
      The client's stages of adoption; (5) Determinants of physical activity; (6)
      Selected educational concepts; (7) Selected strategies of planned maintenance.
      The model provides the practitioner the main work steps of counseling to follow
      and detailed lists of potential factors in each step to be taken into account for
      effective counseling on health-related physical activity. An illustrative case
      history is given on the model's application. The model is shown to incorporate
      central behavioral strategies shown useful in promoting adherence to physical
      activity.

PMID- 10889743
TI  - How to understand a community--community assessment for the promotion of health
      related physical activity.
AB  - A definition of the concept of community is given and the principles and the
      major components of community assessment for health-related physical activity are
      presented. Definitions of community can include a focus on geographic, social or
      cultural elements. Basically community assessment deals with a process having two
      main aspects. The first, quantitative and descriptive aspect consists of a
      community profile, a wellness profile, a behavioural profile and a service
      profile. The second, qualitative and analytical aspect deals with organizational
      capabilities and the community's readiness for change. This information can be
      used for programme planning, implementation, and evaluation in the process of
      community development.

PMID- 10889744
TI  - The versatile nature of physical activity--on the psychological, behavioural and
      contextual characteristics of health-related physical activity.
AB  - This paper presents a comprehensive characterisation of physical activity based
      on psychological, behavioural and contextual aspects. Based on the
      characterisation it suggests a promotional classification of physical activity
      into five categories. The categories are: 1, Occupational activity; 2, Lifestyle
      activity; 3, Recreation activity; 4, Fitness activity; and 5, Sport activity.
      Examples are given of activities in each category and of the related emotional
      aspects, outcome expectations, degree of personal choice and health benefits. The
      importance of the emotional component and the relevance of the outcome
      expectations are discussed and contextual considerations are presented on the
      basis of the promotional classification. The implications of the classification
      for the practice of health-enhancing physical activity promotion are discussed.

PMID- 10889745
TI  - How to develop one's counseling--demonstration of the use of single-case studies
      as a practical tool for evaluating the outcomes of counseling.
AB  - The physical activity patterns of eight single cases of back patients are
      described across a series of counseling sessions and a 12-month follow-up. The
      cases demonstrate the variability of physical activity during the counseling
      period due to random influences in the patient's life and the possibility of
      total relapse of more complicated activity types after counseling. The simple
      behaviors like proper sitting, standing or lifting are shown to be better
      maintained in spite of the random influences in the patient's life. The single
      case study method is demonstrated to serve as a practical tool for evaluating
      one's counseling in the promotion of health-related physical activity.

PMID- 10889746
TI  - How can physical activity be changed--basic concepts and general principles in
      the promotion of health-related physical activity.
AB  - Basic concepts and general principles in the promotion of health-related physical
      activity are presented based on selected behavioral science theories, research
      findings and conceptual analysis. The concepts and principles selected include
      (1) a realistic and flexible concept of physical activity, (2) a pragmatic use of
      the determinants of physical activity, (3) targeting promotion to specific stages
      of adoption at a time, (4) a systematic facilitation of the change process by
      health communications and environmental changes, and (5) a stepwise organization
      of the promotional activities while respecting the target people's freedom of
      choice.

PMID- 10889747
TI  - What is counseling all about--basics in the counseling of health-related physical
      activity.
AB  - Counseling is presented as a professional approach in health care to promote
      physical activity in personal contacts. General principles of counseling are
      introduced with emphasis on client-centeredness, cooperative role relations,
      unconstrained interaction, and goal-oriented proceeding. The contacts with the
      clients or the patients are divided into three categories with different
      preconditions for the extent to which counseling methods can be applied and
      demands placed on the practitioner's counseling skills: 1, On the spot
      information and advice within a single contact; 2, Preplanned way of proceeding
      within a few repeated contacts touching the same topic; 3, Planned period of
      proper counseling sessions. Implications for counseling in physical activity are
      given.

PMID- 10889748
TI  - How to lead a group--practical principles and experiences of conducting a
      promotional group in health-related physical activity.
AB  - In this article the different roles and styles of instruction for the leader of a
      promotional group in physical activity are described. The promotional group is
      defined as one in which group dynamics is used to its maximum in order to
      facilitate permanent change in the members' health-related physical activities.
      Thus e.g., the group forms its own goals on the basis of its members' individual
      needs and aspirations and the group members provide feedback, behavioural models
      and encouragement to each other in their pursuit of change. The leader-instructor
      works in a stepwise fashion from assessment to evaluation to reformulation of
      plans made and monitors closely the stages of adoption of physical activity in
      his or her group. As the group advances the instructor should be ready to
      transfer more and more responsibility to the members.

PMID- 10889749
TI  - How to develop a group curriculum: developing an exercise programme for
      overweight adults.
AB  - This paper reports on work to develop introductory exercise courses for
      sedentary, moderately overweight adults. The aim is to offer a safe and
      motivating programme of physical exercise and, through experiential learning, to
      encourage and facilitate increased physical activity. The core of the programme
      is a course of 10-20 weekly exercise classes. The classes include a variety of
      physical exercises adapted to the special needs of overweight adults (BMI 28-34
      kg/m2) and a number of health-related fitness tests. We outline the underlying
      principles of the exercise courses, their structure and contents, the guidelines
      of instruction, and the use of formative evaluation. In addition, we report on
      the implementation of five weight-reduction courses and six exercise courses
      involving a total of 209 participants. A fairly high level of programme
      acceptability (in terms of attendance rates and personal commitment) and
      programme feasibility (in terms of acceptability, changes in personal orientation
      towards health and weight reduction, and satisfaction among participants) was
      achieved.

PMID- 10889750
TI  - Daily walking and cycling to work: their utility as health-enhancing physical
      activity.
AB  - The substantial health-enhancing potential of physical activity can be realised
      on population level best if people can incorporate physical activity into their
      daily life routines. Physically active commuting to and from work provides a
      promising mode for such activity. In a series of three studies we explored more
      specifically the population prevalence, the physiological effectiveness, and the
      promotional possibilities of commuting to work by walking and cycling in a mid
      size Finnish town. The results of the questionnaire survey indicated that while
      about one-third of the working-age sample commuted by walking or cycling an
      additional one-quarter were in a position to either begin or increase physically
      active commuting. The controlled intervention study showed that this kind of
      moderate-intensity, high-frequency activity improved the health-related fitness
      and selected indices of metabolic health. The promotion project in a large
      industrial plant demonstrated that walking and cycling during work trips can be
      successfully promoted by relatively low cost measures. These experiences suggest
      that physically active commuting to work offers substantial potential as a health
      enhancing measure for working-age population.

PMID- 10889751
TI  - Does physical activity enhance health?
AB  - This paper provides the justification of physical activity promotion for health
      by critically reviewing the recent US Surgeon General's Report. Evidence is
      summarized of the effects of physical activity on physiological responses,
      overall mortality, a number of diseases and disabilities, overall functional
      capacity, and mental health and quality of life. Cumulating evidence suggests
      that the effects be applicable to both genders and to a wide age range. The
      adverse effects of physical activity on health are shown to be small and mostly
      preventable. It is emphasized that substantial health effects can be gained by
      moderate daily physical activity which does not require high skill level nor
      specialized equipment or facilities. It is concluded that the health potential of
      physical activity is substantial due to the high prevalence of inactive lifestyle
      in the populations, the great number of health conditions being affected by
      physical activity, and the feasibility and safety of physical activity as a
      health measure.

PMID- 10889752
TI  - What are groups all about?--basic principles of group work for health-related
      physical activity.
AB  - The basic group processes such as norms, roles, social support, and the
      developmental phases of a group are defined and applied to physical activity
      groups. Three kinds of groups are differentiated for the promotion of health
      related physical activity: on-the-spot information in groups, traditional
      physical activity groups, and interactive promotional groups. The case is
      forwarded that in the promotion of physical activity group work is most
      effective, if it is based on mutual interaction between the group members and
      utilizes group processes. Arguments are presented for the advantage of
      interactive promotional groups to help people adopt health-related physical
      activities.

PMID- 10889753
TI  - How to develop local physical activity promotion programmes with national
      support: the Finnish experience.
AB  - Stimulated by recent research findings regarding the health effects of physical
      activity, an extensive policy development for sports and for health took place in
      Finland in the early 1990s resulting in two national programmes. The 'Finland on
      the Move' programme's aim was to stimulate new local projects by financial
      support, training and consultation services, and media promotion. The evaluation
      of the programme listed several general characteristics of successful local
      projects. The ongoing 'Fit for Life' programme is based on the experience gained
      from the previous programme, but is focused mostly on the 40-60-year-olds as a
      target group, and utilises a more intensive mass media approach. It is concluded
      that the two programmes have been successful in creating plenty of new local
      initiatives and increasing population participation related to physical activity.
      The Finnish experience demonstrates that deliberate efforts to communicate
      scientific knowledge can lead to a better acceptance of physical activity on the
      national level and that well-planned and sensitive state-level support of
      grassroots activities can succeed.

PMID- 10889754
TI  - [Delphi technique: identifying the generic competence required for doctors and
      nurses working in a primary health care].
AB  - This study aims to identify the generic competence required of doctors and nurses
      working in a primary health care. It was based on a series of 3 round of the
      Delphi technique which identified 8 generic competencies: ability to communicate,
      ability to be community oriented, ability in teamwork, management skills,
      educational skills, ability to problem solving, professional skills, ability to
      make-decision. Only the competence management skills there was not consensus by
      doctors. They disagree that this competence is required by them working in
      primary health care.

PMID- 10889755
TI  - [Students' background in the profession and duties in assistant nursing at the
      time of entering the course].
AB  - This descriptive and exploratory study focused on verifying how knowledgeable the
      students of the Auxiliary Nursing Course are regarding their profession and the
      attributes thereof. Results were that, as far as the students are concerned,
      being and attendant involves interpersonal relationship, responsibility, theorist
      scientific know-how and competence.

PMID- 10889756
TI  - [Ethical and legal aspects of the nursing records of organ donors for
      transplant].
AB  - The objective of this study was to verify the ethical and legal aspects
      concerning the documentation of nursing practice in the organ donor's records.
      The records of the 12 organ donors admitted in a Brazilian University Hospital,
      from January/1992 to august/1996 were analysed. The donor consent was reported by
      nurses in 16.7% of the records. Defects that preclude legal value for the
      charting such as missing date or signature, erasure were found in 91.7% of the
      records.

PMID- 10889757
TI  - [Perception of the meaning of the caretaker's function for a group of nurses and
      caretakers: convergences and divergences].
AB  - This study review the of role the caretaker at the pediatric unit while the child
      is in hospital. The opinions of caretaker and nurses were surveyed as for the
      role that the participating family member would have during their stay along with
      the child in hospital. Data were gathered between April and June 1997 in units
      allowing for children to stay together with caretaker, at state hospitals. The
      interviews with the groups were separated by meas of the stafement analysis,
      based on the studies by COSTA (1992), and FRIEDMAN (1986), which allowed us to
      determine six categories: Security & Protection, Caretaking, Recovery, Knowledge,
      Supervision and Guidance, which in turn allowed us to study, although in a modest
      fashion, the agreements and disagreements regarding how our interviews perceive
      the role of the caretaker.

PMID- 10889758
TI  - [Using tools for pain perception assessment in hospitalized pre-school children
      undergoing painful procedures].
AB  - The aim of this study was evaluate the utilization of tools for pain perception
      assessment in 41 hospitalized pre-school children submitted to painful
      procedures: care of wounds or blood extraction. The utilized tools were the faces
      scale, behavioral indicators and words which describe the pain. Most of the pre
      schoolers understood and correctly answered to the faces scale, which can be
      noticed by the crescent movement 0 (no pain) 4 (maximum pain) during the choice
      of faces before and after the painful procedure. Crying, immortality and forehead
      wrinkling were the predominant behavioral indicators, intensified during the
      procedure. Pre-schoolers verbalizations about their pain showed up to be concrete
      terms or evaluative-indicative nature, resulting in variable or weakly precise
      concepts.

PMID- 10889760
TI  - [Hoping for the future child: the father's experience in the intensive care
      unit].
AB  - This study was intended to analyse the experience of the father who have a child
      in an Intensive Care Unit, by applying the qualitative research under the
      phenomenological perspective of Martin Heidegger, it was to identify three themes
      which figured that experience: Transforming the fear into hope, Perceiving
      himself as the person who decides and Acting for his child benefit. These themes
      unveiled the phenomenon SEARCHING A CHANCE FOR THE CHILD TO BECOME, who reveals
      that submits his child to risks and to essential treatments while continuously
      unchanging overcomes his own feelings in order to offer to his child an
      opportunity of full living.

PMID- 10889759
TI  - [Working conditions of traditional birth attendants: some characteristics of
      rural home situations].
AB  - This is a study of qualitative and dialectical approach, which subject is to
      analyze the working conditions of the traditional birth attendants, in a
      reproductive perspective of work, and for this reason, economically undervalued.
      The analysis has been constructed having as central category the work, under
      marxist and feminist premises. Obtained results permit us to state these
      traditional birth attendants do their work in material and financial poor
      conditions, related to transportation, access, and still, working environment.
      The analysis of this practice has given us a possibility to present a discussion
      on some traits of the traditional birth attendant's work, which is characterized
      as a reproductive work, economically undervalued, autonomous and eminently
      feminine. It still configures as a social practice of popular health, legitimated
      by the community. In the rural domestic obstetrics practice, unequal relations
      were in evidence since men and women play different roles in the same occupation,
      being women's responsability the reproduction of the feminine role.

PMID- 10889761
TI  - [Analysis of the method used in the nursing staff performance evaluation at the
      USP University Hospital].
AB  - The aim of this study was to check if the evaluators and evaluated follow the
      operational criterion that direct the nursing staffs evaluation of HU; to the
      identify the graduation conferred to obrigatory and optional forecasters by
      evaluators and evaluated; to identify the optional forecaster chosen by
      evaluators and evaluated and prepare the researches to a change at the process of
      nursing staff's evaluation of HU. The results showed that different functional
      categories had similar points of view; there were high level of agreement between
      them; both values attribution as optional forecaster selection. It's demonstrated
      that there's coherence at the process of nursing staff's performance evaluation,
      the evaluators shaves with evaluated the same pre-supposition about the purpose
      and importance of the forecasters insert in the instrument of performance
      evaluation.

PMID- 10889762
TI  - [Risk factors for pressure ulcer: suggestions for prevention].
AB  - Pressure ulcers is one of the most severe complication in the spinal cord injured
      patients begin the prevention aspects and the early identification of the risk
      factors are imperative action for the nursing assistance of these patients. This
      study evaluated the nursing care plans for these patients that at the time of the
      study were already included in the rehabilitation program in order to identify
      the risk factors for the pressure ulcer development by analysing the nursing
      documentation adapting the Taxonomy of NANDA. Evaluate the nursing procedures
      proposed to the diagnosis risk for impaired skin integrity. The identified risk
      factors are referred to the physical alterations determinate by the neurologic
      lesion, wound's history and initial lesions. The proposed nursing procedures were
      sixteen (16) that emphasized patient and family's instructions on body cleaning,
      position on bed and wheel chair based on the diagnosis established.

PMID- 10889763
TI  - [Follow-up of nurses graduated from the University of Sao Paulo: their
      integration into intensive care units].
AB  - The purposes of this research was to identify the activities developed by the
      nurses after undergraduation course at the School of Nursing of the University of
      Sao Paulo and to characterize their insertion in Intensive Care Units (ICUs), in
      relation to have been or not their first area of job, their previous experience
      in ICU, the specific initial training and difficulties faced to take on the ICU
      activities. The population was composed by nurses graduated between 1991 and
      1995. A rol of names, addresses and telephone numbers was obtained at the school
      office. Two hundred and thirty five questionnaires were sent by mail and 117
      (49.8%) were returned. The majority of the respondents (90.5%) were working as
      nurses, mainly in hospitals, which was the most indicated area of work (76.2%).
      Almost half of the informants (47.0%) said they worked or were working in ICUs
      and for 54.5% of them, this was their first job; 52.8% had no previous experience
      in ICU. Although 64.1% of these nurses had received a specific initial training,
      some difficulties to take on the ICU activities were faced: lack of knowledge and
      psychomotor skills (45.4%), handling equipments (25.8%) and relationship with the
      multiprofessional and the nursing team (8.2%).

PMID- 10889764
TI  - [Problems and solutions for patients with hypertension].
AB  - This study aims to identify difficulties and facilities of the patients in
      following the treatment of the arterial hypertension; and, to verify differences
      that exist between those difficulties and facilities in two moments of the
      trajectory--in the ambulatorial treatment and in the hospital stay. For this
      quantitative, descriptive study, 34 patients with medical diagnosis of arterial
      hypertension or its complications were interviewed, being 17 registered in the
      ambulatorial unit and 17 hospitalized in the nephrology unit. The results of the
      study revealed that, in general, there were no differences among the difficulties
      and the facilities referred by the patients for the following of the treatment in
      the two studied moments. The difficulties and facilities pointed out by the
      patients refer to the financing of the treatment (medication purchase and
      expenses with transport); accessibility to the service (easiness in marking
      medical consultation and distance of the service of health); change of alimentary
      habit (hipossodic diet), and the importance of the family support in this
      trajectory.

PMID- 10889765
TI  - [AIDS information systems: limits and possibilities].
AB  - The article makes an analysis of the current System of Information (SI) in AIDS,
      aiming the difficulties with that was confronted when looking for to characterize
      the way as it happened and it developed in 1995 the epidemic of the AIDS in the
      Regional Administration of Health of Pirituba-Perus (ARS-8) of the municipal
      district of Sao Paulo. Some are enumerated critics that the Epidemic Surveillance
      and the SI they come suffering in the last years, such as the centralization and
      the disaggregation of the information; the data that contemplate aspects
      eminently biological, the use of complex forms. These subjects, added to the
      difficulties that were imposed to the he/she/it to look for to characterize the
      epidemic in the area, he/she revealed that the system, just as her found
      structured, it hindered the characterization of the epidemic and the systematic
      accompaniment for the local levels of health. He/she gets himself the attention
      for the need of revision of the purpose of the SI in AIDS, of the nature and of
      the quality of the collected data. It is reiterated the importance of the
      integration of the several databases partner-demographics of the focus
      microlocalizado of SI for the District of Health.

PMID- 10889766
TI  - [Head injury victims and their return to work after 6 months to 1 year].
AB  - A prospective and longitudinal study about head injury victims was carried out in
      order to identify their return to productivity after 6 months and 1 year post
      trauma and to analyze the relationship between their return to work and their
      educational level as well as to determine the relationship between their return
      to work and their type of job before the onset of the injury. Of the 72 patients
      who were students or employees pre-injury, or housewives at the time of injury,
      the majority (73.6%) had returned to productivity 6 months after onset of injury.
      Of the victims who had returned to productivity, 25.0% had changed their original
      occupations or reported significant problems when returning to productivity.
      Baseline return was achieved in 48.6% of the victims at 6 months. Return to
      productivity was higher at 1 year after injury than at 6 months. When the
      relationship between return to work and educational level and job type was
      analyzed, return to work was not related to educational level or job type.

PMID- 10889767
TI  - Insights into the management of erectile dysfunction: Part I.
AB  - It is estimated that as many as 30 million men in the United States suffer from
      erectile dysfunction (ED). Because ED is so widespread, especially among the
      older population, it is imperative that this disorder be recognized as an
      important and manageable health problem.

PMID- 10889768
TI  - Relationship between health promotion lifestyle profiles and patient outcomes of
      biofeedback therapy for urinary incontinence.
AB  - Computerized EMG biofeedback therapy is a conservative treatment option for
      patients with urge incontinence, frequency, and certain types of stress urinary
      incontinence. Patient motivation to follow through with treatment and home
      exercise program is an important factor for successful therapy. The Health
      Promotion Lifestyle Profile (HPLP) II measures the frequency of health-promoting
      behaviors. A preliminary study of 45 patients suggested the HPLP II is a valid
      and reliable predictor of patient motivation. Further research is needed to
      ascertain if the tool may serve to predict patients' commitment to biofeedback
      and subsequent success with therapy. Effective screening of patients can also
      reduce overuse of services and ensure appropriate use of percapitated dollars.

PMID- 10889769
TI  - Urologic applications of the holmium laser.
AB  - The holmium laser has various urologic applications. It is important for urologic
      nurses and associates to be familiar with the laser physics and safety
      recommendations of the holmium laser, as well as to understand the applications
      and surgical techniques associated with this therapy.

PMID- 10889770
TI  - Development and testing of a scale to measure self-efficacy for pelvic muscle
      exercises in women with urinary incontinence.
AB  - Previous research has demonstrated that pelvic muscles exercises can reduce or
      eliminate incontinence. Active patient participation is a key component; thus, a
      person's self-efficacy is important to successful outcomes. This methodologic
      study resulted in a 23-item scale incorporating ideas from self-efficacy theory.
      Psychometric analysis of reliability and validity were satisfactory.

PMID- 10889771
TI  - Getting ready for certification: staging genitourinary malignancies.

PMID- 10889772
TI  - Template for a good regional programme of basic surgical training.

PMID- 10889773
TI  - Everything you have ever wanted to know about flexible training and more....

PMID- 10889774
TI  - NCCGs.

PMID- 10889775
TI  - Skills courses in the Raven Department of Education.

PMID- 10889776
TI  - A comparison of reports from referees chosen by authors or journal editors in the
      peer review process.
AB  - The aim was to analyse the peer review process by comparing reports produced by
      referees selected by journal editors, with those of referees selected by the
      authors of a scientific manuscript. Some 104 consecutive papers from the UK
      submitted to the British Journal of Surgery (BJS) were included. Of these, 102
      were reviewed blind both by referees chosen by the journal editors, and referees
      chosen by the paper's principal author. Manuscripts were marked using a standard
      sheet for four basic aspects: originality, clinical/scientific importance,
      clarity and analysis; a final overall recommendation about possible publication
      was given. The time taken and the number of completed referee reports were
      similar in each group. Referees chosen by the BJS editors were more critical
      (scored higher) of the submitted articles. Mean scores for all domains were
      higher than for authors' referees, significantly for scientific importance (p =
      0.009) and decision to publish (p = 0.029). In conclusion, reports produced by
      referees selected by BJS editors were more critical than those chosen by authors
      of the papers. Authors might argue that this reduced their chance of publication
      but constructive criticism might improve the final article and assist editors to
      make decisions about acceptance or rejection.

PMID- 10889777
TI  - What's in a name?

PMID- 10889778
TI  - Sub-specialty training in general surgery: are we producing what the hospitals
      need?

PMID- 10889779
TI  - Can changes to junior surgical jobs improve training and make a career in surgery
      more attractive?
AB  - Surgical training has been extensively revised in recent years and new challenges
      are emerging due to a shorter length of training with fewer opportunities for
      hands-on experience. Junior doctors' hours are likely to be reduced further, some
      even advocate shift systems. How do junior surgical jobs affect the desire of
      young doctors to become surgeons? How can further improvements be made to make
      surgical training more attractive and effective? This study aims to answer these
      questions by asking the junior doctors concerned.

PMID- 10889780
TI  - The potential and costs of videoconferencing in dental education, dental
      vocational training and MFDS preparation.
AB  - This paper considers the potential role of videoconferencing technology for
      postgraduate dental and medical education. Drawing on work from the University of
      Bristol Dental School, it presents an analysis of the potential cost savings
      achievable by using videoconferencing compared to traditional face-to-face
      teaching across a range of scenarios. A summary of the feedback from trainees is
      also provided.

PMID- 10889781
TI  - The Association of Surgeons of Great Britain and Ireland.

PMID- 10889782
TI  - Launching a new continuing professional development programme from the Raven
      Department of Education.
AB  - In recent years the quality agenda has taken centre stage in the medical arena.
      Coupled with this, the present era of rapid scientific and technological advance
      means that all professionals are engaged in a continuing process of life-long
      learning. With the pace of change increasing all the time, new thinking
      challenges conventional wisdom and traditional methods are constantly being
      superseded. Continuing professional development is the only way for surgeons to
      stay at the leading edge in such as challenging environment at every stage in
      their career, to progress--to be participants in these changes rather than merely
      observers.

PMID- 10889783
TI  - The 'morbidity and mortality' meeting--no longer defensible as surgical audit.

PMID- 10889784
TI  - Low standard of hospital records.

PMID- 10889785
TI  - Obesity, insulin resistance and diabetes--a worldwide epidemic.
AB  - Obesity is now commonly defined in adults as a BMI > 30 kg/m2. The prevalence of
      obesity in established market economies (Europe, USA, Canada, Australia, etc.)
      varies greatly, but a weighed estimate suggests an average prevalence in the
      order of 15-20%. The prevalence in these countries generally shows increasing
      trends over time. Obesity is also relatively common in Latin America, but much
      less so in sub-Saharan Africa and Asia where the majority of the world population
      lives. Nevertheless obesity rates are increasing there as well and, more
      importantly, rates of diabetes are increasing even more quickly, particularly in
      Asian countries. The risks of type 2 diabetes mellitus in these countries tend to
      increase sharply at levels of BMI generally classified as acceptable in European
      and North American white people. There have been suggestions to adopt specific
      classifications of obesity in Asians (e.g. BMI 23 for overweight and 25 or 27
      kg/m2 for obesity) and this will greatly affect the prevalence estimates of
      obesity worldwide (currently at about 250 million people). Particularly for
      health promotion purposes BMI may be replaced by a classification based on waist
      circumference, but also specific classifications for different ethnic groups may
      be necessary. The number of diabetics has been projected to increase from 135
      million in 1995 to 300 million in 2025. Much of this increase will be seen in
      Asia. In summary, both obesity and type 2 diabetes are common consequences of
      changing lifestyles (increased sedentary lifestyles and increased energy density
      of diets). Both are potentially preventable through lifestyle modification on a
      population level, but this requires a coherent and multifaceted strategy. Such
      strategies are not developed or implemented. These developments point toward the
      great urgency to develop global and national plans for adequate prevention and
      management of obesity and type 2 diabetes mellitus.

PMID- 10889786
TI  - Obesity--a genetic disease of adipose tissue?
AB  - Although the rapid increase in the prevalence of obesity in many countries
      suggests that environmental factors (mainly overeating and physical inactivity)
      play the most important role in the development of overweight, it is very likely
      that genetic factors also contribute. It appears that one major gene in
      combination with one or several minor genes constitute the genetic components
      behind excess accumulation of body fat in most obese individuals. However,
      monogenic obesity has been described in a few families due to changes in leptin,
      leptin receptor, prohormone convertase, pro-opiomelanocortin or melanocortin-4
      receptor. None of the monogenic variants is of great importance for common human
      obesity; the latter genes are unknown so far. Results from genomic scans suggest
      that major obesity genes are located on chromosomes 2, 10, 11 and 20. Studies of
      candidate genes indicate that the minor obesity genes control important functions
      of adipose tissue, and that structural variance in these genes may alter adipose
      tissue function in a way that promotes obesity. Such genes are beta 2- and beta 3
      adrenoceptors, hormone-sensitive lipase, tumour necrosis factor alpha, uncoupling
      protein-1, low-density lipoprotein receptor, and peroxisome proliferator
      activator receptor gamma-2. Some of these genes may promote obesity by gene-gene
      interactions (for example beta 3-adrenoceptors and uncoupling protein-1) or gene
      environment interactions (for example beta 2-adrenoceptors and physical
      activity). Some are important for obesity only among women (for example beta 2-
      and beta 3-adrenoceptors, low-density lipoprotein receptor and tumour necrosis
      factor alpha). Few 'non-adipose' genes have so far shown a firm association to
      common human obesity, which could suggest that the important genes for the
      development of excess body fat also control adipose tissue function.

PMID- 10889787
TI  - Energy balance and weight regulation: genetics versus environment.
AB  - The prevalence of obesity is reaching epidemic proportions in many industrialized
      countries. There is growing evidence that, even if the trigger of this epidemic
      is found in changes in the environment, genes are interacting with the
      environment to cause weight gain. Studies of twins reared apart indicate that
      approximately two-thirds of the variability in BMI is attributed to genetic
      factors. From prospective studies in Pima Indians we can ascribe 12% of the
      variability in BMI to metabolic rate, 5% to fat oxidation, and another probable
      10% to the level of spontaneous physical activity. These data indicate that at
      least 40% of the variability in BMI is related to genetic factors involved in the
      regulation of food intake and/or volitional activity. This indicates that the
      most likely successful therapy for obesity may target pathways of the regulation
      of food intake. Similarly, an environment favouring engagement in physical
      activity should be promoted.

PMID- 10889788
TI  - Population studies of diet and obesity.
AB  - Population-based research on diet, obesity and the metabolic syndrome is faced
      with accumulating evidence of biases that may profoundly affect results. One
      potential source of bias, which is often neglected in nutritional epidemiology,
      arises from self-selected study populations. Subjects who agree to participate in
      surveys may be at less risk of metabolic syndrome than those who refuse.
      Analogous to observations in adult populations, studies of schoolchildren have
      also yielded clear evidence of self-selection. Whether such selection patterns
      influence analytical results depends on how the biases relate to the dependent
      and independent variables being studied. Systematic dietary reporting error is
      another source of bias in studies of nutritional risk factors for disease. While
      obesity-related under-reporting bias is now well documented, less is known about
      whether specific foods and nutrients are disproportionately affected. However,
      two studies employing biomarkers for protein have suggested that obese subjects
      under-reported the proportion of energy from fat plus carbohydrate. This should
      alert epidemiologists to the possibility that a dual reporting bias may be
      present in studies of diet and disease: general under-reporting among obese
      subjects compounded by food-specific errors. In summary, biases due to self
      selection and selective dietary under-reporting may produce consequences in
      epidemiological studies that are both unpredictable and complex. We conclude this
      review with recent findings involving dietary fat intake and regional adiposity
      in a population-based study of women. These preliminary results may have
      etiological relevance to the development of metabolic syndrome, but multiple
      biases of the type described previously may also be operating.

PMID- 10889789
TI  - The role of dietary fat in body fatness: evidence from a preliminary meta
      analysis of ad libitum low-fat dietary intervention studies.
AB  - The role of high-fat diets in weight gain and obesity has been questioned because
      of inconsistent reports in the literature concerning the efficacy of ad libitum
      low-fat diets to reduce body weight. We conducted a meta-analysis of weight loss
      occurring on ad libitum low-fat diets in intervention trials, and analysed the
      relationship between initial body weight and weight loss. We selected controlled
      trials lasting more than 2 months comparing ad libitum low-fat diets with a
      control group consuming their habitual diet or a medium-fat diet ad libitum
      published from 1966 to 1998. Data were included from 16 trials with a duration of
      2-12 months, involving 1728 individuals. No trials on obese subjects fulfilled
      the inclusion criteria. The weighted difference in weight loss between
      intervention and control groups was 2.55 kg (95% CI, 1.5-3.5; P < 0.0001). Weight
      loss was positively and independently related to pre-treatment body weight (r =
      0.52, P < 0.05) and to reduction in the percentage of energy as fat (0.37 kg/%, P
      < 0.005) in unweighted analysis. Extrapolated to a BMI of about 30 kg/m2 and
      assuming a 10% reduction in dietary fat, the predicted weight loss would be 4.4
      kg (95% CI, 2.0 to -6.8 kg). Because weight loss was not the primary aim in 12 of
      the 16 studies, it is unlikely that voluntary energy restriction contributed to
      the weight loss. Although there is no evidence that a high intake of simple
      sugars contributes to passive overconsumption, carbohydrate foods with a low
      glycaemic index may be more satiating and exert more beneficial effects on
      insulin resistance and cardiovascular risk factors. Moreover, an increase in
      protein content up to 25% of total energy may also contribute to reducing total
      energy intake. In conclusion, a low-fat diet, high in protein and fibre-rich
      carbohydrates, mainly from different vegetables, fruits and whole grains, is
      highly satiating for fewer calories than fatty foods. This diet composition
      provides good sources of vitamins, minerals, trace elements and fibre, and may
      have the most beneficial effect on blood lipids and blood-pressure levels. A
      reduction in dietary fat without restriction of total energy intake prevents
      weight gain in subjects of normal weight and produces a weight loss in overweight
      subjects, which is highly relevant for public health.

PMID- 10889790
TI  - Routes to obesity: phenotypes, food choices and activity.
AB  - Gain in body weight over a number of years could be achieved through cumulative
      positive energy balances. These positive balances could come about through
      adjustments in the various components of energy expenditure or fuel utilization,
      together with shifts in food selection or eating patterns leading to adjustments
      in macronutrient intake. This means that many combinations of intake and
      expenditure could lead to a positive energy balance; these combinations can be
      called routes to body weight gain. However, these routes are difficult to trace
      by studying random samples of individuals. Previous investigations have found a
      clear association between high fat consumption and the occurrence of obesity, and
      although a high fat intake is a strong behavioural risk factor for weight gain,
      the relationship does not constitute a biological inevitability. Some normal
      weight and lean individuals appear to eat a high-fat diet. To investigate reasons
      for this we have studied individuals initially defined by particular clusters of
      dietary characteristics related to fat and carbohydrate consumption. Habitual
      high-fat (HF) and low-fat (LF) consumers have been termed phenotypes. Various
      aspects of energy expenditure (physiological and behavioural) and energy intake
      were measured in these individuals with contrasting profiles. HF phenotypes had
      high intakes of fatty foods and an overall higher energy intake than LF. However,
      these groups of young adult males had similar BMIs and percentage body fat. The
      HF had a significantly higher resting metabolic rate (RMR) and a lower RQ,
      together with high plasma fasting leptin levels, and a higher sleeping heart
      rate. In HF individuals the physical activity level was somewhat lower and they
      had significantly more periods of sedentary behaviour than LF subjects. Although
      HF individuals appear to be more vulnerable to developing obesity, both
      phenotypes carry particular risk factors and protective factors for weight gain.
      The use of phenotypes has allowed the identification of different potential
      routes to weight gain. Different strategies are required to prevent age-related
      increase in body weight in these quite different individuals.

PMID- 10889791
TI  - Genetics of the metabolic syndrome.
AB  - The clustering of cardiovascular risk factors such as abdominal obesity,
      hypertension, dyslipidaemia and glucose intolerance in the same persons has been
      called the metabolic or insulin-resistance syndrome. In 1998 WHO proposed a
      unifying definition for the syndrome and chose to call it the metabolic syndrome
      rather than the insulin-resistance syndrome. Although insulin resistance has been
      considered as a common denominator for the different components of the syndrome,
      there is still debate as to whether it is pathogenically involved in all of the
      different components of the syndrome. Clustering of the syndrome in families
      suggests a genetic component. It is plausible that so-called thrifty genes, which
      have ensured optimal storage of energy during periods of fasting, could
      contribute to the phenotype of the metabolic syndrome. Common variants in a
      number of candidate genes influencing fat and glucose metabolism can probably,
      together with environmental triggers, increase susceptibility to the syndrome.
      Among these, the genes for beta 3-adrenergic receptor, hormone-sensitive lipase,
      lipoprotein lipase, IRS-1, PC-1, skeletal muscle glycogen synthase, etc. appear
      to increase the risk of the metabolic syndrome. In addition, novel genes may be
      identified by genome-wide searches.

PMID- 10889792
TI  - The metabolic syndrome--a neuroendocrine disorder?
AB  - Central obesity is a powerful predictor for disease. By utilizing salivary
      cortisol measurements throughout the day, it has now been possible to show on a
      population basis that perceived stress-related cortisol secretion frequently is
      elevated in this condition. This is followed by insulin resistance, central
      accumulation of body fat, dyslipidaemia and hypertension (the metabolic
      syndrome). Socio-economic and psychosocial handicaps are probably central
      inducers of hyperactivity of the hypothalamic-pituitary adrenal (HPA) axis.
      Alcohol, smoking and traits of psychiatric disease are also involved. In a minor
      part of the population a dysregulated, depressed function of the HPA axis is
      present, associated with low secretion of sex steroid and growth hormones, and
      increased activity of the sympathetic nervous system. This condition is followed
      by consistent abnormalities indicating the metabolic syndrome. Such 'burned-out'
      function of the HPA axis has previously been seen in subjects exposed to
      environmental stress of long duration. The feedback control of the HPA axis by
      central glucocorticoid receptors (GR) seems inefficient, associated with a
      polymorphism in the 5' end of the GR gene locus. Homozygotes constitute about 14%
      of Swedish men (women to be examined). Such men have a poorly controlled cortisol
      secretion, abdominal obesity, insulin resistance and hypertension. Furthermore,
      polymorphisms have been identified in the regulatory domain of the GR gene that
      are associated with elevated cortisol secretion; polymorphisms in dopamine and
      leptin receptor genes are associated with sympathetic nervous system activity,
      with elevated and low blood pressure, respectively. These results suggest a
      complex neuroendocrine background to the metabolic syndrome, where the kinetics
      of the regulation of the HPA axis play a central role.

PMID- 10889793
TI  - Polyunsaturated fatty acid regulation of gene transcription: a mechanism to
      improve energy balance and insulin resistance.
AB  - This review addresses the hypothesis that polyunsaturated fatty acids (PUFA),
      particularly those of the n-3 family, play essential roles in the maintenance of
      energy balance and glucose metabolism. The data discussed indicate that dietary
      PUFA function as fuel partitioners in that they direct glucose toward glycogen
      storage, and direct fatty acids away from triglyceride synthesis and assimilation
      and toward fatty acid oxidation. In addition, the n-3 family of PUFA appear to
      have the unique ability to enhance thermogenesis and thereby reduce the
      efficiency of body fat deposition. PUFA exert their effects on lipid metabolism
      and thermogenesis by upregulating the transcription of the mitochondrial
      uncoupling protein-3, and inducing genes encoding proteins involved in fatty acid
      oxidation (e.g. carnitine palmitoyltransferase and acyl-CoA oxidase) while
      simultaneously down-regulating the transcription of genes encoding proteins
      involved in lipid synthesis (e.g. fatty acid synthase). The potential
      transcriptional mechanism and the transcription factors affected by PUFA are
      discussed. Moreover, the data are interpreted in the context of the role that
      PUFA may play as dietary factors in the development of obesity and insulin
      resistance. Collectively the results of these studies suggest that the metabolic
      functions governed by PUFA should be considered as part of the criteria utilized
      in defining the dietary needs for n-6 and n-3 PUFA, and in establishing the
      optimum dietary ratio for n-6:n-3 fatty acids.

PMID- 10889794
TI  - Obesity and the metabolic syndrome: the San Antonio Heart Study.
AB  - Obesity, especially visceral adiposity, is a major determinant of the development
      of type 2 diabetes. Both visceral adiposity and insulin resistance are strongly
      related to cardiovascular risk factors in diabetic and non-diabetic subjects. One
      of the areas where the correlation between visceral fat (upper body adiposity)
      and cardiovascular risk is most apparent is the prediabetic state. We have
      recently shown that only prediabetic subjects (those who later develop type 2
      diabetes) who are insulin resistant and with upper body adiposity have increased
      triglycerides, decreased HDL cholesterol and high blood pressure.

PMID- 10889795
TI  - Visceral fat and insulin resistance--causative or correlative?
AB  - The association between abdominal fat accumulation and risk of chronic diseases,
      including type II diabetes and coronary heart disease, has long been recognized.
      Insulin resistance may be a key factor in this link. Many studies have pointed to
      an association between insulin resistance and intra-abdominal fat accumulation
      (visceral obesity). However there is no clear proof of a causal link between
      visceral fat accumulation and insulin resistance. In assessing the probability of
      a causal link, it is useful to consider potential mechanisms. One such potential
      causal link is the release of non-esterified fatty acids from visceral fat into
      the portal vein, so that they have direct effects on hepatic metabolism. Visceral
      fat has been shown in many studies to exhibit a high rate of lipolysis compared
      with subcutaneous fat depots. However, if the idea that visceral fat releases
      fatty acids into the portal vein at a high rate is examined critically, a number
      of difficulties appear. Not least of these is the fact that continued high rates
      of lipolysis should lead to the disappearance of the visceral fat depot, unless
      these high rates of fat mobilization are matched by high rates of fat deposition.
      There is far less evidence for high rates of fat deposition in visceral adipose
      tissue, and some contrary evidence. Evidence for high rates of visceral lipolysis
      in vivo from studies involving catheterization of the portal vein is not strong.
      If this potential link is discounted, then other reasons for the relationship
      between visceral fat and insulin resistance must be considered. One is that there
      is no direct causal link, but both co-correlate with some other variable. A
      possibility is that this other variable is subcutaneous abdominal fat, which
      usually outweighs intra-abdominal fat several-fold. Subcutaneous fat probably
      plays the major role in determining systemic plasma non-esterified fatty acid
      concentrations, which are relevant in determining insulin resistance. In
      conclusion, there is at present no proof of a causal link between visceral fat
      accumulation and insulin resistance, or the associated metabolic syndrome. The
      possibility of co-correlation with some other factor, such as subcutaneous
      abdominal fat accumulation, must not be forgotten.

PMID- 10889796
TI  - Fatty acids and insulin secretion.
AB  - It has long been recognized that acute elevation of non-esterified fatty acids
      (NEFA) stimulates insulin secretion to a moderate extent both in vitro and in
      vivo. The effects of longer-term exposure to elevated fatty acids have, however,
      been investigated only recently. Our own studies in the rat have documented the
      time dependence of NEFA effects, with inhibition of glucose-induced insulin
      secretion being apparent after 6-24 h in vivo exposure to Intralipid or in vitro
      exposure to palmitate, oleate and octanoate. Evidence indicates that the
      inhibitory effects are coupled to fatty acid oxidation in B-cells, with ensuing
      reduction in glucose oxidation, in parallel with diminished activity of the
      pyruvate dehydrogenase enzyme. These findings were essentially confirmed in human
      pancreatic islets. In the db/db mouse, a model of type 2 diabetes with obesity,
      evidence was obtained for elevated NEFA playing a significant role in decreased
      glucose-induced insulin secretion. Evidence also indicates that elevated NEFA
      inhibit insulin biosynthesis and increase the proinsulin:insulin ratio of
      secretion. Results on experimentally induced elevations of NEFA in non-diabetic
      and diabetic humans are thus far inconclusive. Further studies are needed to
      ascertain the impact of elevated NEFA on insulin secretion in clinical settings.

PMID- 10889797
TI  - Diet composition and insulin action in animal models.
AB  - Critical insights into the etiology of insulin resistance have been gained by the
      use of animal models where insulin action has been modulated by strictly
      controlled dietary interventions not possible in human studies. Overall, the
      literature has moved from a focus on macronutrient proportions to understanding
      the unique effects of individual subtypes of fats, carbohydrates and proteins.
      Substantial evidence has now accumulated for a major role of dietary fat subtypes
      in insulin action. Intake of saturated fats is strongly linked to development of
      obesity and insulin resistance, while that of polyunsaturated fats (PUFAs) is
      not. This is consistent with observations that saturated fats are poorly oxidized
      for energy and thus readily stored, are poorly mobilized by lipolytic stimuli,
      impair membrane function, and increase the expression of genes associated with
      adipocyte profileration (making their own home). PUFAs have contrasting effects
      in each instance. It is therefore not surprising that increased PUFA intake in
      animal models is associated with improved insulin action and reduced adiposity.
      Less information is available for carbohydrate subtypes. Early work clearly
      demonstrated that diets high in simple sugars (in particular fructose) led to
      insulin resistance. However, again attention has rightly shifted to the very
      interesting issue of subtypes of complex carbohydrates. While no differences in
      insulin action have yet been shown, differences in substrate flux suggest there
      could be long-term beneficial effects on the fat balance of diets enhanced in
      slowly digested/resistant starches. A new area of major interest is in protein
      subtypes. Recent results have shown that rats fed high-fat diets where the
      protein component was from casein or soy were insulin-resistant, but when the
      protein source was from cod they were not. These are exciting times in our
      growing understanding of dietary factors and insulin action. While it has been
      clear for some time that 'oils ain't oils', the same is now proving true for
      carbohydrates and proteins.

PMID- 10889798
TI  - Dietary fat and insulin action in humans.
AB  - A high intake of fat may increase the risk of obesity. Obesity, especially
      abdominal obesity, is an important determinant of the risk of developing insulin
      resistance and non-insulin-dependent diabetes mellitus. It is suggested that a
      high proportion of fat in the diet is associated with impaired insulin
      sensitivity and an increased risk of developing diabetes, independent of obesity
      and body fat localization, and that this risk may be influenced by the type of
      fatty acids in the diet. Cross-sectional studies show significant relationships
      between the serum lipid fatty acid composition, which at least partly mirrors the
      quality of the fatty acids in the diet, and insulin sensitivity. Insulin
      resistance, and disorders characterized by insulin resistance, are associated
      with a specific fatty acid pattern of the serum lipids with increased proportions
      of palmitic (16:0) and palmitoleic acids (16:1 n-7) and reduced levels of
      linoleic acid (18:2 n-6). The metabolism of linoleic acid seems to be disturbed
      with increased proportions of dihomo-gamma linolenic acid (20:3 n-6) and a
      reduced activity of the delta 5 desaturase, while the activities of the delta 9
      and delta 6 desaturases appear to be increased. The skeletal muscle is the main
      determinant of insulin sensitivity. Several studies have shown that the fatty
      acid composition of the phosholipids of the skeletal muscle cell membranes is
      closely related to insulin sensitivity. An increased saturation of the membrane
      fatty acids and a reduced activity of delta 5 desaturase have been associated
      with insulin resistance. There are several possible mechanisms which could
      explain this relationship. The fatty acid composition of the lipids in serum and
      muscle is influenced by diet, but also by the degree of physical activity,
      genetic disposition, and possibly fetal undernutrition. However, controlled
      dietary intervention studies in humans investigating the effects of different
      types of fatty acids on insulin sensitivity have so far been negative.

PMID- 10889799
TI  - Dietary carbohydrates and insulin action in humans.
AB  - The metabolic syndrome represents a vicious cycle whereby insulin resistance
      leads to compensatory hyperinsulinaemia, which maintains normal plasma glucose
      but may exacerbate insulin resistance. Excess insulin secretion may eventually
      reduce beta-cell function due to amyloid deposition, leading to raised blood
      glucose and further deterioration of beta-cell function and insulin sensitivity
      via glucose toxicity. Reducing postprandial glucose and insulin responses may be
      a way to interrupt this process, but there is disagreement about the dietary
      approach to achieve this. Glucose and insulin responses are determined primarily
      by the amount of carbohydrate consumed and its rate of absorption. Slowly
      absorbed, low glycaemic-index (GI) foods are associated with increased HDL
      cholesterol and reduced risk of type 2 diabetes. There is some evidence that low
      GI foods improve insulin sensitivity in humans, although studies using
      established techniques (glucose clamp or frequently sampled intravenous glucose
      tolerance test) have not been done. Low carbohydrate diets have been suggested to
      be beneficial in the treatment of the metabolic syndrome because of reduced
      postprandial insulin. However, they may increase fasting glucose and impair oral
      glucose tolerance--effects which define carbohydrate intolerance. The effects of
      low carbohydrate diets on insulin sensitivity depend on what is used to replace
      the dietary carbohydrate, and the nature of the subjects studied. Dietary
      carbohydrates may affect insulin action, at least in part, via alterations in
      plasma free fatty acids. In normal subjects a high-carbohydrate/low-GI breakfast
      meal reduced free fatty acids by reducing the undershoot of plasma glucose,
      whereas low-carbohydrate breakfasts increased postprandial free fatty acids. It
      is unknown if these effects occur in insulin-resistant or diabetic subjects. Thus
      further work needs to be done before a firm conclusion can be drawn as to the
      optimal amount and type of dietary carbohydrate for the treatment of the
      metabolic syndrome.

PMID- 10889800
TI  - Is long-term weight loss possible?
AB  - Any intervention which causes negative energy balance is guaranteed to be
      efficacious in producing weight loss, which will continue while there is negative
      energy balance or be maintained as long as the new energy balance is maintained.
      In clinical practice compliance is rarely 100% so the efficiency of even the most
      efficacious treatment is usually low. However, recent evidence-based guidelines
      have recognized the clinical benefits of moderate (5-10%) weight loss, which is
      achievable using a variety of interventions. Long-term studies of 'weight loss'
      are, in reality, combinations of weight loss (usually completed in 1-6 months)
      followed by variable weight maintenance, set in the context of progressive adult
      weight gain in an obesogenic environment. Few studies have adopted specific and
      separate strategies for weight loss and weight maintenance. Meta-analyses
      conducted by non-expert methodologists have failed to recognize these
      distinctions, and have criticized the available research without understanding
      the different needs of studies with weight change as the outcome variable, which
      require randomized controlled trials (RCT), and those with weight loss as the
      treatment, intended to improve metabolic or biomedical outcome measures. An RCT
      design is inapplicable to studies of biomedical end points (e.g. cardiac risk
      factors) when weight loss is the treatment. Because fixed weight loss cannot be
      prescribed there is always a range of weight changes in any study, and single
      sample studies with regression analysis provide the best design. An RCT study
      design does not give useful information about clinical value as the control group
      is always 'treated' to some extent. Placebo- (or control)-subtracted differences
      are misleading because in an RCT all subjects recruited to active treatment,
      including non-responders, are continued on treatment for the full duration of the
      study. In routine clinical practice, treatments are changed in the light of early
      experience as a therapeutic trial to optimize the results for each individual,
      and audit is required to evaluate 'long term weight loss'.

PMID- 10889801
TI  - Diet, blood pressure and hypertension.
AB  - Prevention of hypertension, and control of blood pressure in patients with
      hypertension, are necessary for the reduction of cardiovascular morbidity and
      mortality. Lifestyle modifications are one of the most important tools for
      effective lowering of blood pressure. Most randomized controlled studies have
      shown that even a modest weight loss of 3-9% is associated with a significant
      reduction in systolic and diastolic blood pressure of roughly 3 mm Hg in
      overweight people. Limitation of sodium chloride in food has historically been
      considered the critical change for reducing blood pressure. Changes in sodium
      intake do affect blood pressure in older persons and in patients with
      hypertension and diabetes, whereas its role in population blood pressure has
      proven controversial. Recent meta-analyses indicate that adequate intake of
      minerals, e.g. potassium and probably calcium, rather than restriction of sodium,
      should be the focus of dietary recommendations. Although epidemiological data
      point to a direct relation between the intake of saturated fat, starch and
      alcohol, as well as an inverse relationship to the intake of omega-3 fatty acids
      and protein, our knowledge about macronutrients and blood pressure is scanty. It
      may well prove more productive to look at food instead of placing emphasis on
      single nutrients. Thus the Dietary Approaches to Stop Hypertension (DASH)
      demonstrates that a diet rich in fruits, vegetables, low-fat dairy products,
      fibre and minerals (calcium, potassium and magnesium) produces a potent
      antihypertensive effect. Such a diet is not very restrictive and should not
      produce compliance problems. Further high-quality research on the influence of
      macronutrients and food will yield data for updated recommendations, enabling
      better prevention and control of the blood pressure problem.

PMID- 10889802
TI  - Dietary treatment of thrombogenic disorders related to the metabolic syndrome.
AB  - The increased risk of coronary heart disease associated with the metabolic
      syndrome may be partially explained by prothrombotic deviations of the
      haemostatic system. Individuals with insulin resistance, dyslipidaemia and
      obesity are characterized by elevated plasma fibrinogen and factor VII coagulant
      activity levels and raised concentrations of plasminogen-activator inhibitor, the
      main inhibitor of endogenous fibrinolysis. These haemostatic abnormalities may be
      corrected with dietary treatment of the underlying clinical disorder. Dietary
      trials of diseased and healthy volunteers suggest that the optimal antithrombotic
      diet is a low-fat diet with a high content of foods rich in complex carbohydrates
      and dietary fibre. The dietary fatty acid composition has a profound effect on
      blood lipids, but seems of minor importance for the haemostatic system.

PMID- 10889803
TI  - Genetic determinants of plasma lipid response to dietary intervention: the role
      of the APOA1/C3/A4 gene cluster and the APOE gene.
AB  - Polymorphisms at the APOA1/C3/A4 gene cluster and the APOE gene have been
      extensively studied in order to examine their potential association with plasma
      lipid levels, coronary heart disease risk and more recently with inter-individual
      variability in response to dietary therapies. Although the results have not been
      uniform across studies, the current research supports the concept that variation
      at these genes explains a significant, but still rather small, proportion of the
      variability in fasting and postprandial plasma lipid responses to dietary
      interventions. This information constitutes the initial frame to develop panels
      of genetic markers that could be used to predict individual responsiveness to
      dietary therapy for the prevention of coronary heart disease. Future progress in
      this complex area will come from experiments carried out using animal models, and
      from carefully controlled dietary protocols in humans that should include the
      assessment of several other candidate gene loci coding for products that play a
      relevant role in lipoprotein metabolism (i.e. APOB, CETP, LPL, FABP2, SRBI, ABC1
      and CYP7).

PMID- 10889804
TI  - The Finnish Diabetes Prevention Study.
AB  - The aim of the Finnish Diabetes Prevention Study is to assess the efficacy of an
      intensive diet-exercise programme in preventing or delaying type 2 diabetes in
      individuals with impaired glucose tolerance (IGT) and to evaluate the effect of
      the programme on the risk factors of atherosclerotic vascular diseases and the
      incidence of cardiovascular events. In this ongoing study, a total of 523
      overweight subjects with IGT based on two oral glucose tolerance tests were
      randomized to either an intervention group or a control group. The main measure
      in the intervention group is individual dietary advice aimed at reducing weight
      and intake of saturated fat and increasing intake of dietary fibre. The
      intervention subjects are individually guided to increase their level of physical
      activity. The control group receives general information about the benefits of
      weight reduction, physical activity and healthy diet in the prevention of
      diabetes. A pilot study began in 1993, and recruitment ended in 1998. By the end
      of April 1999 there were 65 new cases of diabetes, 34 drop-outs and one death.
      The weight reduction was greater (-4.6 kg) at 1 year in the intervention group (n
      = 152) than in the control group (n = 143, -0.9 kg, P < 0.0001), and this
      difference was sustained in the second year of follow-up. At 1 year 43.4% and at
      2 years 41.8% of the intervention subjects had achieved a weight reduction of at
      least 5 kg, while the corresponding figures for the control subjects were 14.0
      and 12.0% (P < 0.001 between the groups). At 1 year the intervention group showed
      significantly greater reductions in 2 h glucose, fasting and 2 h insulin,
      systolic and diastolic blood pressure, and serum triglycerides. Most of the
      beneficial changes in cardiovascular risk factors were sustained for 2 years.
      These interim results of the ongoing Finnish Diabetes Prevention Study
      demonstrate the efficacy and feasibility of the lifestyle intervention programme.

PMID- 10889805
TI  - Dietary treatment of the metabolic syndrome--the optimal diet.
AB  - The treatment of the metabolic syndrome aims to improve insulin sensitivity and
      correct/prevent the associated metabolic and cardiovascular abnormalities. Since
      many individuals with the metabolic syndrome are overweight, dietary treatment
      should be primarily focused on weight reduction. This approach can improve
      insulin sensitivity and exert beneficial effects on all the other abnormalities
      clustering in the syndrome. Insulin sensitivity can also be influenced by diet
      composition. In this respect, the specific effects of the quality of dietary fat
      are of great interest, given the considerable evidence in experimental animals
      that saturated fat in the diet may lead to insulin resistance. In man, there is
      indirect evidence that a higher saturated fat intake is associated with impaired
      insulin action. Human studies have also attempted to evaluate the relationship
      between total fat intake and insulin sensitivity. They are consistent in showing
      that fat intake is correlated with both plasma insulin values (positively) and
      insulin sensitivity (negatively). However, these correlations are largely
      mediated by body weight. Conversely, intervention studies are consistent in
      showing that when total fat intake is moderately increased (from 20 to 40%), no
      major effect is observed on insulin sensitivity. We have recently undertaken a
      large, multicentre intervention study in 162 healthy individuals given either a
      high-saturated-fat or a high-monounsaturated-fat diet for 3 months. It shows that
      a high-monounsaturated-fat diet significantly improves insulin sensitivity
      compared to a high-saturated-fat diet. However, this beneficial effect of
      monounsaturated fat disappears when total fat intake exceeds 38% of total energy.
      Independently of its effects on insulin sensitivity, diet composition can
      influence the factors clustering in the metabolic syndrome. Dietary carbohydrate
      increases blood glucose levels, particularly in the postprandial period, and
      consequently also insulin levels and plasma triglycerides. The detrimental
      effects of a high-carbohydrate diet on plasma glucose/insulin, triglyceride/HDL
      or fibrinolysis occur only when carbohydrate foods with a high glycaemic index
      are consumed, while they are abolished if the diet is based largely on fibre
      rich, low-glycaemic-index foods. In conclusion, weight reduction is a powerful
      measure for the treatment of metabolic syndrome. Moreover, the diet for the
      treatment of the metabolic syndrome should be limited in the intake of saturated
      fat, while high fibre/low-glycaemic-index foods should be used without specific
      limitations. Moderate amounts of monounsaturated fat could be permitted as they
      do not induce detrimental metabolic effects.

PMID- 10889806
TI  - Low glycaemic-index foods.
AB  - Accumulating data indicate that a diet characterized by low glycaemic-index (GI)
      foods not only improves certain metabolic ramifications of insulin resistance,
      but also reduces insulin resistance per se. Epidemiological data also suggest a
      protective role against development of non-insulin-dependent diabetes mellitus
      and cardiovascular disease. A major disadvantage in this connection is the
      shortage of low-GI foods, and many common starchy staple foods, such as bread
      products, breakfast cereals and potato products, have a high GI. Studies in our
      laboratory show that it is possible to significantly lower the GI of starchy
      foods, for example by choice of raw material and/or by optimizing the processing
      conditions. Such low-GI foods may or may not influence glucose tolerance at a
      subsequent meal. Consequently, certain low-GI breakfasts capable of maintaining a
      net increment in blood glucose and insulin at the time of the next meal
      significantly reduced post-prandial glycaemia and insulinaemia following a
      standardized lunch meal, whereas others had no 'second-meal' impact. These
      results imply that certain low-GI foods may be more efficient in modulating
      metabolism in the long term. Although the literature supports a linear
      correlation between the GI and insulinaemic index (II) of foods, this is not
      always the case. Consequently, milk products elicited elevated IIs,
      indistinguishable from a white bread reference meal, despite GIs in the lower
      range. This inconsistent behaviour of milk products has not been acknowledged,
      and potential metabolic consequences remain to be elucidated.

PMID- 10889807
TI  - Dietary fibre, lente carbohydrates and the insulin-resistant diseases.
AB  - Several epidemiological studies link consumption of fibre-rich foods to a reduced
      risk of type 2 diabetes and CHD. The 'fibre hypothesis' suggested that this was a
      direct effect of fibre. However, fibre-rich foods contain different types of
      fibre as well as other potentially beneficial compounds, and many foods naturally
      high in fibre have low glycaemic and insulinaemic indices, possibly due to food
      form. The question therefore emerges as to the effect of isolated fibre per se on
      insulin sensitivity, lipids and other risk factors associated with the metabolic
      syndrome. Many beneficial effects are seen with pharmacological doses of isolated
      viscous soluble fibre, including improved insulin sensitivity, decreased LDL
      cholesterol levels and decreased clotting factors. Similar effects are seen with
      low glycaemic-index foods. In contrast, insoluble non-viscous cereal fibre is not
      seen to act directly on risk factors when taken in refined foods such as in
      milled flour. Since cereal fibre, the major type of fibre in western diets, does
      not directly act on the risk factors for the metabolic syndrome, the question
      remains as to possible mechanisms. Until now, fibre and the nature and processing
      of the starch and particle size have been seen as the main determinants of the
      metabolic response to starchy foods. However, fibre-rich foods also have an
      increased protein-to-carbohydrate ratio. Hence we suggest that the protective
      effect of fibre may also be due to increased vegetable protein content, which may
      act directly to reduce clotting factors and oxidized LDL-cholesterol levels.

PMID- 10889808
TI  - How to implement dietary changes to prevent the development of metabolic
      syndrome.
AB  - Changing dietary intake is a major challenge to individuals, households and the
      general public. Promoting the consumption of diets that are low in fat and high
      in fruits, vegetables and starchy carbohydrate, and managing overweight and
      central obesity, are important dietary strategies for the prevention of metabolic
      syndrome. Educational, behavioural and motivational tactics are required to help
      people achieve overall dietary change. These strategies might usefully be based
      on intervention models which incorporate behavioural theories and goals through
      personal, multiple contact with individuals or in small groups, using active
      involvement and specific behaviour-change strategies. Two particular aspects,
      namely the impact of computer-generated, personalized nutrition education and
      social support networks (e.g. family, health centre and community) provide useful
      adjuncts to traditional dietary counselling and might usefully be incorporated
      into diet- and lifestyle-change programmes for community-based and individualized
      approaches for disease prevention. The use of moderate energy-deficit diets,
      modest targets for weight loss (and maintenance) which can be sustained over the
      long term, and increased physical activity probably offers the most feasible
      approach for intervention aimed at reducing overall body weight.

PMID- 10889809
TI  - Can dietary intervention produce long-term reduction in insulin resistance?
AB  - Insulin sensitivity is potentially enhanced by a range of diet-related changes
      including reduction of visceral adiposity, a reduction in saturated fatty acids,
      and possibly a redistribution of the proportions of various unsaturated fatty
      acids. While there is evidence to suggest that lifestyle changes can reduce the
      risk of progression of impaired glucose tolerance to type 2 diabetes, there are
      no clinical trials which have conclusively demonstrated that any measure can
      reduce insulin resistance in the long term to an extent that can prevent the
      development of type 2 diabetes and other clinical complications. Evidence
      concerning the possibilities for reducing visceral adiposity and altering the
      nature of dietary fat are therefore considered. Attempts to achieve prolonged and
      substantial weight reduction in adults have not been encouraging, and it may be
      that preventing further weight gain is the most realistic target in this age
      group. In childhood the attempts have been more successful. The development of
      new approaches to achieving behavioural change and an environment which
      facilitates physical activity and appropriate food choices will be essential for
      more successful individual and population attempts to facilitate reduction in
      insulin resistance by weight loss. Changes in the nature of dietary fat appear to
      be more easily achieved. This is already a component of dietary advice aimed at
      cardiovascular risk reduction, and should be reinforced now with a view to also
      achieving a reduction in insulin resistance.

PMID- 10889810
TI  - What can industry do to facilitate dietary and behavioural changes?
AB  - The food industry has five important roles in facilitating needed dietary and
      behavioural changes. Two of these roles are direct ones. Industry can increase
      the availability of a wide variety of basic commodities and new foods that help
      consumers meet dietary recommendations. It is also responsible for developing and
      formulating appealing, healthy and effective food products that decrease risks of
      chronic degenerative disease. Industry also plays an indirect role in
      facilitating dietary change by motivating consumers to select and prepare foods
      that will result in healthy dietary patterns. It can also participate in
      coalitions to facilitate other behaviours that decrease risks. Finally, it can
      collaborate actively in applied and fundamental research to further our
      understanding of the associations between food and health.

PMID- 10889811
TI  - Strategies to prevent the metabolic syndrome at the population level: role of
      authorities and non-governmental bodies.
AB  - The remarkable increase over the past 40 years in some chronic diseases,
      including the metabolic syndrome, has increased the demand for government and
      international policies to encourage various approaches to decrease the risk of
      these disease. There are some prerequisites for working out successful national
      food and nutrition policies. Firstly, it is necessary to have a clear picture of
      the dietary pattern in a country and its associated public health problems. Based
      on these data, nutrient recommendations and goals are formulated by international
      or national scientific committees. Governments should translate these nutrient
      goals into food goals and eventually into national dietary guidelines. The means
      by which the national authorities can implement a nutrition policy include
      fortification and supplementation. Equally important are educational and
      informative tools, such as labelling on the packed food products including
      information about ingredients and nutrient content. With respect to the metabolic
      syndrome, this implies nutrient recommendations regarding the intake of fat and
      carbohydrates (energy per cent) and dietary fibre; dietary guidelines regarding
      balance between energy intake and expenditure; decreased consumption of products
      rich in fat and increased consumption of cereals and other products rich in
      dietary fibre, etc.; recommendations from the authorities regarding nutrient
      labelling (content of fat and dietary fibre) on relevant products; and nutrient
      and health claims and other aids (symbols) as tools to make it easier for
      consumers to select the appropriate food products.

PMID- 10889812
TI  - Recent advances in immunohistochemistry in the diagnosis of ovarian neoplasms.
AB  - This leader reviews recent advances in immunohistochemistry that are useful in
      the diagnosis of ovarian neoplasms. These include the value of different
      anticytokeratin antibodies in the distinction between a primary ovarian
      adenocarcinoma and a metastatic adenocarcinoma, especially of colorectal origin.
      These antibodies have also helped to clarify the origin of the peritoneal disease
      in most cases of pseudomyxoma peritonei. The value of antibodies against so
      called tumour specific antigens, such as CA125 and HAM56, in determining the
      ovarian origin of an adenocarcinoma is also reviewed. In recent years, several
      studies have investigated the value of a variety of monoclonal antibodies in the
      diagnosis of ovarian sex cord stromal tumours and in the distinction between
      these neoplasms and their histological mimics. These antibodies include those
      directed against inhibin, CD99, Mullerian inhibiting substance, relaxin like
      factor, melan A, and calretinin. Of these, anti-alpha inhibin appears to be of
      most diagnostic value. It is stressed that these antibodies should always be used
      as part of a larger panel and not in isolation.

PMID- 10889813
TI  - Glycated haemoglobin in the year 2000.

PMID- 10889814
TI  - When should a coroner's inquest be held? The Manchester guidelines for
      pathologists.

PMID- 10889815
TI  - ACP Best practice no 159. Examination of large intestine resection specimens.
AB  - Macroscopic examination of large intestinal resection specimens by the surgical
      pathologist provides important diagnostic and prognostic information. This review
      summarises current recommended protocols and evidence based guidelines for gross
      description, dissection, and histological block selection in both neoplastic and
      non-neoplastic colorectal disease. Specific lesions discussed include colorectal
      cancer, polypectomies and polyposis syndromes, and inflammatory bowel disease.
      Microscopic examination is briefly described, with emphasis on certain pitfalls
      that might be encountered in routine practice. A section covering special
      techniques for the investigation of occult bleeding is included.

PMID- 10889816
TI  - Evaluation of a new amplified enzyme immunoassay (EIA) for the detection of
      Chlamydia trachomatis in male urine, female endocervical swab, and patient
      obtained vaginal swab specimens.
AB  - AIMS: To compare the performance of a new generation dual amplified enzyme
      immunoassay (EIA) with a molecular method for the diagnosis of Chlamydia
      trachomatis, using a range of urogenital samples, and to assess the reliability
      of testing self collected vaginal specimens compared with clinician collected
      vaginal specimens. METHODS: Two population groups were tested. For the first
      population group, first void urine samples were collected from 193 male patients
      with urethritis, and endocervical swabs were collected from 187 high risk
      commercial sex workers. All urine and endocervical specimens were tested by a
      conventional assay (IDEIA chlamydia), a new generation amplified immunoassay
      (IDEIA PCE chlamydia), and the Amplicor polymerase chain reaction (PCR).
      Discrepant results obtained among the three sample types were confirmed using a
      nested PCR test with a different plasmid target region. For the second population
      group, four swab specimens, including one patient obtained vaginal swab, two
      clinician obtained endocervical swabs, and one clinician obtained vaginal swab,
      were collected from 91 high risk sex workers. Self collected and clinician
      collected vaginal swabs were tested by IDEIA PCE chlamydia. Clinician obtained
      endocervical swabs were assayed by IDEIA PCE chlamydia and Amplicor PCR. RESULTS:
      The performance of the IDEIA PCE chlamydia test was comparable to that of the
      Amplicor PCR test when male urine and female endocervical swab specimens were
      analysed. The relative sensitivities of IDEIA, IDEIA PCE, and Amplicor PCR on
      male first void urine specimens were 79.3%, 91.4%, and 100%, respectively. The
      relative sensitivities of the three tests on female endocervical specimens were
      85.0%, 95.0%, and 100%, respectively. The positivity rates for patient collected
      vaginal specimens and clinician collected vaginal specimens by IDEIA PCE were
      25.2% and 23.1%, respectively, whereas those for clinician collected endocervical
      swabs by PCR and IDEIA PCE were both 27.5%. CONCLUSIONS: IDEIA PCE chlamydia is a
      lower cost but sensitive alternative test to PCR for testing male urine samples
      and female endocervical swabs. In addition, self collected or clinician collected
      vaginal specimens tested by IDEIA PCE chlamydia are a reliable alternative to
      analysing endocervical specimens.

PMID- 10889817
TI  - Comparison of in house polymerase chain reaction with conventional techniques for
      the detection of Mycobacterium tuberculosis DNA in granulomatous lymphadenopathy.
AB  - AIMS: To evaluate the usefulness of the devR based polymerase chain reaction
      (PCR) in the detection of Mycobacterium tuberculosis in lymph node aspirates and
      tissues of lymphadenitis and to compare PCR with conventional diagnostic
      techniques. SUBJECTS AND METHODS: Coded specimens of fine needle aspirates and
      biopsies from 22 patients with tuberculous lymphadenitis, 14 patients with non
      tubercular lymphadenitis, and nine patients with granulomatous lymphadenitis were
      processed and subjected to analysis by PCR, smear microscopy, M tuberculosis
      culture, histology, and cytology. RESULTS: Tuberculous lymphadenitis was
      correctly diagnosed by PCR in 18 patients, by culture in five patients, by
      histology in 13 patients, and by cytology in seven patients. PCR gave two false
      positive results in 14 patients with non-tubercular lymphadenitis. The
      sensitivity of the conventional techniques was significantly higher with biopsies
      (17 of 22 specimens; 77%) than with fine needle aspirates (nine of 22 specimens;
      41%). However, the sensitivity of PCR was not significantly higher with biopsies
      (68%) in comparison with fine needle aspirates (55%). The sensitivity of either
      biopsy PCR or fine needle aspirate PCR was not significantly different from that
      of either histology combined with culture or cytology combined with culture. The
      overall combined specificity of PCR was 86%. Mycobacterium tuberculosis DNA was
      detected in six of nine patients with granulomatous lymphadenitis. CONCLUSION:
      PCR is the most sensitive single technique available to date for the
      demonstration of M tuberculosis in specimens derived from patients with a
      clinical suspicion of tuberculous lymphadenitis. The value of PCR lies in its use
      as an adjunct test in the diagnosis of tuberculous lymphadenitis, particularly in
      those patients where conventional methods fail. Because fine needle aspiration is
      not an invasive procedure, it is the procedure of choice, and PCR should be
      performed initially on these samples. Excisional biopsy histology and PCR should
      be recommended only for patients in whom fine needle aspirate PCR is negative or
      when there is discrepancy with the clinical impression.

PMID- 10889818
TI  - Aspergillus antigen testing in bone marrow transplant recipients.
AB  - AIMS: To assess the clinical usefulness of a commercial aspergillus antigen
      enzyme linked immunosorbent assay (ELISA) in the diagnosis of invasive
      aspergillosis (IA) in bone marrow transplant recipients, and to compare it with a
      commercial latex agglutination (LA) test. METHODS: In total, 2026 serum samples
      from 104 bone marrow transplant recipients were tested. These comprised 67 sera
      from seven patients who had died with confirmed IA, 268 sera from nine patients
      who had died with suspected IA, and 1691 sera from 88 patients with no clinical,
      radiological, or microbiological signs of IA. RESULTS: The ELISA was more
      sensitive than the LA test. All patients who were ELISA positive were also LA
      positive, and a positive LA result never preceded a positive ELISA. Twelve of 16
      patients with confirmed or suspected IA were ELISA positive on two or more
      occasions, compared with 10 of 15 who were LA positive. ELISA was positive before
      LA in five patients (range, 2-14 days), and became positive on the same day in
      the remainder. Aspergillus antigen was detected by ELISA a median of 15 days
      before death (range, 4-233). Clinical and/or radiological evidence of IA was
      noted in all patients, and a positive ELISA was never the sole criterion for
      introduction of antifungal treatment. Two samples (one from each of two patients
      without IA) gave false positive results. CONCLUSIONS: The aspergillus ELISA is a
      specific indicator of invasive aspergillosis if the criterion of two positive
      samples is required to confirm the diagnosis. However, the test is insufficiently
      sensitive to diagnose aspergillosis before other symptoms or signs are apparent,
      and hence is unlikely to lead to earlier initiation of antifungal treatment. It
      is therefore unsuitable for screening of asymptomatic patients at risk of
      invasive aspergillosis, but does have a useful role in confirming the diagnosis
      in symptomatic patients.

PMID- 10889819
TI  - What is a natural cause of death? A survey of how coroners in England and Wales
      approach borderline cases.
AB  - AIM: Many deaths fall in the "grey" area between those that are clearly natural
      and those that are unnatural. There are no guidelines to help doctors in dealing
      with such cases and death certification is often arbitrary and inconsistent. In
      an attempt to initiate debate on these difficult areas, and with the ultimate aim
      of achieving national consensus, the views of coroners in England and Wales were
      sought. METHODS: Sixteen clinical scenarios, with causes of death, were
      circulated to all coroners in England and Wales. For each case they were asked to
      provide a verdict, with explanation. The deaths fell into three groups: (1)
      postoperative, (2) a combination of trauma and natural disease, and (3)
      infectious disease. RESULTS: Sixty four questionnaires were returned. There was
      near consensus (> 80% concordance) in only two of the 16 cases. In five, there
      was no significant agreement between coroners in the verdicts returned ("natural
      causes" versus "misadventure/accidental"). These included all three cases in
      which death resulted from a combination of trauma and natural disease (a fall
      after a grand mal fit; falls resulting in fractures of bones affected by
      metastatic carcinoma and osteoporosis), bronchopneumonia after hip replacement
      for osteoarthritis, and new variant Creutzfeldt-Jakob disease. The comments made
      for each case indicate that the variation between coroners in whether or not to
      hold an inquest, and the verdict arrived at, reflect the lack of a definition for
      natural causes, together with differences in the personal attitudes of each
      coroner. CONCLUSIONS: There is considerable variation in the way in which
      coroners approach these borderline cases, many of which are common in clinical
      practice. This study indicates a need for discussion, working towards a national
      consensus on such issues. It highlights the importance of good communication
      between coroners and medical staff at a local level.

PMID- 10889820
TI  - Laboratory assessment of the status of Her-2/neu protein and oncogene in breast
      cancer specimens: comparison of immunohistochemistry assay with fluorescence in
      situ hybridisation assays.
AB  - AIM: To evaluate the clinical usefulness of three commercially available assays
      for Her-2/neu oncogene and protein measurements. The Her-2/neu protein is
      overexpressed, mostly as a result of gene amplification, in 20-30% of human
      breast cancers, and has been shown to have prognostic and predictive value for
      treatment with chemotherapy or the new monoclonal antibody, Herceptin. METHODS:
      An immunohistochemistry (IHC) assay using the Dako polyclonal antibody A0485,
      which measures the Her-2/neu protein, was compared with two new Food and Drug
      Administration (FDA) approved fluorescence in situ hybridisation (FISH) assays-
      INFORM and PathVysion, in a cohort of 52 formalin fixed, paraffin wax embedded
      breast tissues. These tissues were selected randomly from 84 consecutive
      infiltrating breast cancer specimens, which were first stratified according to
      the Her-2/neu protein levels as measured by IHC. RESULTS: The two FISH assays
      achieved a 98% concordance rate: 14 specimens (27%) showed Her-2/neu gene
      amplification and 37 specimens (71%) showed no Her-2/neu gene amplification. The
      PathVysion assay had certain advantages over the INFORM assay. In contrast, the
      IHC assay detected Her-2/neu overexpression in a high percentage of cases,
      including 13 high positive specimens (25%) and 13 medium positive specimens
      (25%). Although 10 of these 13 IHC high positive specimens showed gene
      amplification by FISH, nine of 13 IHC medium positive specimens showed no gene
      amplification. Statistical analyses showed that the differences between IHC and
      FISH assays were primarily in the specimens with medium positive IHC, but
      negative FISH results. CONCLUSIONS: Because of the increasing importance of the
      Her-2/neu oncogene and oncoprotein in the clinical management of patients with
      breast cancer, the accurate and consistent evaluation of Her-2/neu status is
      crucial. This study suggests that the best approach is to combine both IHC and
      FISH assays; that is, to use the IHC assay as a triage step, followed by the
      PathVysion FISH assay to analyse the IHC medium and high positive cases.

PMID- 10889822
TI  - The importance of IL-6 protein expression in primary human renal cell carcinoma:
      an immunohistochemical study.
AB  - AIMS: Interleukin 6 (IL-6) is produced by some renal carcinoma cell lines in
      vitro. This might be biologically important because IL-6 is a cytokine of
      particular interest, owing to its involvement in the growth of renal cell
      carcinoma. In this study, the expression of IL-6 protein in tissue samples from
      primary renal cell carcinoma was analysed, and then its clinical importance was
      examined. METHODS: The distribution of IL-6 in renal cell carcinoma was examined
      by means of an immunohistochemical method in 47 untreated primary renal cell
      carcinoma samples. The search for a significant difference between histological
      patterns, Furhman's grading system, TNM classification, and IL-6 protein
      expression was carried out. RESULTS: Immunohistochemistry demonstrated that IL-6
      is expressed in 70% of primary tumours. There was no significant difference in
      the tumour size and grade between renal cell carcinomas with or without IL-6
      expression. However, a relatively large number of high grade tumours expressed IL
      6. CONCLUSION: The importance of IL-6 expression with regard to tumour size/local
      growth is questionable because IL-6 has been correlated with the development of
      metastatic disease. These data suggest that the production of IL-6 could exert a
      growth inhibitory effect on primary renal cell carcinoma.

PMID- 10889821
TI  - No detection of enteroviral genome in the myocardium of patients with
      arrhythmogenic right ventricular cardiomyopathy.
AB  - AIMS: Despite the evidence of familial occurrence, chromosomal gene mapping, and
      apoptosis as a mechanism of myocyte death, the aetiopathogenesis of
      arrhythmogenic right ventricular cardiomyopathy (ARVC) remains speculative.
      Because of the frequent histological finding of focal inflammatory infiltrates,
      the hypothesis of an infective myocarditis aetiology has been put forward. The
      aim of this investigation was to test this hypothesis. The presence of
      enteroviruses was investigated by a highly sensitive and specific molecular
      technique. METHODS: Endomyocardial tissue samples from 20 patients with ARVC (11
      male, nine female; mean age, 40 years; SD, 16) and 20 control subjects with other
      cardiac diseases were analysed using reverse transcription and nested polymerase
      chain reaction (PCR). Myocardial samples obtained from four patients with
      enteroviral myocarditis and coxsackie B3 virus infected cells were used as
      positive controls. RESULTS: Endomyocardial biopsy was diagnostic for ARVC in all
      patients: myocardial atrophy was seen, with less than 45% residual myocytes. Foci
      of inflammatory infiltrates were seen in four biopsies, and the cells were
      identified by immunohistochemistry as mainly T cells. All samples, from both
      patients with ARVC and subjects with other cardiac diseases, were negative for
      enteroviral genome by means of nested PCR. CONCLUSION: These findings indicate
      that enteroviruses are not involved in the aetio-pathogenesis of ARVC. Future
      molecular studies should investigate the presence of other infective agents, as
      well as their possible role in triggering apoptosis.

PMID- 10889823
TI  - Histopathological changes associated with high intensity focused ultrasound
      (HIFU) treatment for localised adenocarcinoma of the prostate.
AB  - AIMS: Investigation of the histopathological changes in prostatectomy specimens
      of patients with prostate cancer after high intensity focused ultrasound (HIFU)
      and identification of immunohistochemical markers for tissue damage after HIFU
      treatment. METHODS: Nine patients diagnosed with adenocarcinoma of the prostate
      underwent unilateral HIFU treatment seven to 12 days before radical
      prostatectomy. The prostatectomy specimens were analysed histologically.
      Immunohistochemical staining and electron microscopy were performed to
      characterise more subtle phenotypic changes. RESULTS: All prostatectomy specimens
      revealed well circumscribed HIFU lesions at the dorsal side of the prostate lobe
      treated. Most epithelial glands in the centre of the HIFU lesions revealed signs
      of necrosis. Glands without apparently necrotic features were also situated in
      the HIFU lesions, raising the question of whether lethal destruction had
      occurred. This epithelium reacted with antibodies to pancytokeratin, prostate
      specific antigen (PSA), and Ki67, but did not express cytokeratin 8, which is
      indicative of severe cellular damage. Ultrastructural examination revealed
      disintegration of cellular membranes and cytoplasmic organelles consistent with
      cell necrosis. HIFU treatment was incomplete at the ventral, lateral, and dorsal
      sides of the prostate lobe treated. CONCLUSIONS: HIFU treatment induces a
      spectrum of morphological changes ranging from apparent light microscopic
      necrosis to more subtle ultrastructural cell damage. All HIFU lesions are marked
      by loss of cytokeratin 8. HIFU does not affect the whole area treated, leaving
      vital tissue at the ventral, lateral, and dorsal sides of the prostate.

PMID- 10889824
TI  - Immunohistochemical analysis of human CD5 positive B cells: mantle cells and
      mantle cell lymphoma are not equivalent in terms of CD5 expression.
AB  - CD5 is expressed by most T cells and a subset of B cells. Human CD5 positive B
      cells are present in fetal lymphoid tissue, their frequency decreasing with fetal
      age. In adult human tissues, CD5 positive B cells have been reported to be
      present in the germinal centre and mantle zone. Malignancies of CD5 positive B
      cells include mantle cell lymphoma and chronic lymphocytic leukemia. This report
      describes an immunohistochemical staining technique used to visualise the
      expression of CD5 by B cells in human fetal intestine, tonsil, and mantle cell
      lymphoma. B cells in fetal intestine, tonsillar epithelium, and mantle cell
      lymphoma all had a similar high intensity of CD5 expression. In contrast, CD5 B
      cells in the mantle and germinal centre expressed very small amounts of CD5,
      below the threshold of the technique. Therefore, mantle cells and mantle cell
      lymphoma are not equivalent in terms of CD5 expression.

PMID- 10889825
TI  - Myelomatous involvement of the dura mater: a rare complication of multiple
      myeloma.
AB  - A case of myelomatous involvement of the dura mater is reported. The patient
      presented with blurring of vision in the right visual field and left sided facial
      numbness. A magnetic resonance imaging scan of the head revealed extensive
      infiltration of the dura mater. Cerebrospinal fluid (CSF) analysis showed no
      plasmacytosis and although there was a raised CSF protein concentration, no
      paraprotein band was detected, despite the presence of serum paraprotein. The
      infiltration of the dura mater is likely to have arisen by spread from contiguous
      bone lesions, contrasting with the pattern of spread seen in myelomatous
      involvement of the leptomeninges, which probably occurs through haematogenous
      seeding of the meninges. Leptomeningeal involvement is associated with a very
      poor prognosis; however, this patient had a favourable response to combined
      chemotherapy and cranial radiotherapy, suggesting that myelomatous involvement of
      the dura mater should be considered as a distinct complication of myeloma.

PMID- 10889826
TI  - A technique for the evaluation of failed fallopian tube ligation with metal
      clips.
AB  - The evaluation of fallopian tubes after failed tubal ligation can be difficult
      because conventional histopathological techniques are unable to section the metal
      clips when in situ. Once the clips have been removed, any evidence of tube
      patency is lost. This report describes a technique of embedding and sectioning
      that enables sections to be made while the metal clips are still in situ. This is
      a modification of a method first described to embed mineralised bone and involves
      the use of plastic embedding and a diamond saw. Using this technique, a permanent
      record is made of the tube location and patency.

PMID- 10889827
TI  - Development of a competency based training programme to support multidisciplinary
      working in a combined biochemistry/haematology laboratory.
AB  - The aim of this study was to develop a competency based training programme to
      support multidisciplinary working in a combined biochemistry and haematology
      laboratory. The training programme was developed to document that staff were
      trained in the full range of laboratory tests that they were expected to perform.
      This programme subsequently formed the basis for the annual performance review of
      all staff. All staff successfully completed the first phase of the programme.
      This allowed laboratory staff to work unsupervised at night as part of a partial
      shift system. All staff are now working towards achieving a level of competence
      equivalent to the training level required for state registration by the Council
      for Professions Supplementary to Medicine. External evaluation of the training
      programme has included accreditation by the Council for Professions Supplementary
      to Medicine and reinspection by Clinical Pathology Accreditation (UK) Ltd. The
      development of a competency based training system has facilitated the
      introduction of multidisciplinary working in the laboratory. In addition, it
      enables the documentation of all staff to ensure that they are fully trained and
      are keeping up to date, because the continuing professional development programme
      in use in our laboratory has been linked to this training scheme. This approach
      to documentation of training facilitated a recent reinspection by Clinical
      Pathology Accreditation (UK) Ltd.

PMID- 10889828
TI  - Prevalence of HIV and hepatitis C markers among a cadaveric population in Milan.

PMID- 10889829
TI  - Providing progesterone for pregnancy: control of cholesterol flux to the side
      chain cleavage system.
AB  - Progesterone, which is required to support human gestation, is derived initially
      from the corpus luteum and subsequently from the placenta. The rate-limiting step
      in progesterone synthesis is the delivery of cholesterol to the mitochondrial
      cholesterol side-chain cleavage system. The steroidogenic acute regulatory
      protein (StAR) mediates this process in the corpus luteum, whereas in the
      placenta, which does not express StAR, a StAR homologue, MLN64, may accomplish
      this function. StAR expression is regulated in the ovary at the transcriptional
      level by a cAMP-activated signal transduction system and StAR activity is also
      increased acutely by protein kinase A-mediated phosphorylation. These long-term
      (transcriptional) and short-term (post-translational, that is, phosphorylation)
      mechanisms govern luteal steroidogenic activity. The StAR protein has two key
      functional domains. The StAR C-terminal domain increases cholesterol movement to
      cytochrome P450scc by promoting sterol desorption from the sterol-rich outer
      mitochondrial membrane, driving it to the relatively sterol-poor inner membrane.
      The N-terminal domain mitochondrial targeting sequence directs the StAR protein
      to the mitochondria.

PMID- 10889830
TI  - Endocrine and paracrine-autocrine regulation of the human corpus luteum during
      the mid-luteal phase.
AB  - Human corpora lutea undergo an extremely rapid period of growth, development and
      regression during the course of non-fertile cycles. The tissue consists of
      steroidogenic (parenchymal) and non-steroidogenic (stromal) cells. In women and
      other primates, steroid hormone production by corpora lutea depends on the
      presence of pituitary-derived LH. Nevertheless, there is also intra-luteal
      regulation of steroid synthesis. Steroidogenic luteal cells and non-steroidogenic
      cells interact via endocrine and paracrine pathways, and by contact-dependent
      pathways (gap junctions). Thus, hormones and locally produced factors including
      steroids, growth factors, cytokines, reactive oxygen species and nitric oxide may
      modulate luteal lifespan. The factors regulating regression and rescue of the
      corpus luteum are not understood completely. This review describes the expression
      of two representative intragonadal peptides that may influence luteal regression
      (interleukin 1 beta) and luteal rescue (steroidogenic acute regulatory protein).

PMID- 10889831
TI  - The plasma membrane transformation of uterine epithelial cells during pregnancy.
AB  - This review discusses the diversity of placentation mechanisms and examines the
      extensive alterations that occur in the plasma membrane of uterine epithelial
      cells during early pregnancy in many species. Ultrastructural, biochemical and
      morphological studies reveal that similar membrane alterations occur in many
      species, despite the diversity in the type of placenta that is formed ultimately.
      As these morphological and molecular alterations in the plasma membrane occur
      across species and are found basolaterally as well as apically, the term 'plasma
      membrane transformation' is proposed, which also emphasizes that alterations in
      this membrane during early pregnancy are not just an occurrence at attachment,
      but are an ongoing process during much of early pregnancy.

PMID- 10889832
TI  - Cytokines in implantation.
AB  - Implantation is a process that involves development, attachment and invasion of
      the blastocyst into the endometrium. Successful implantation requires appropriate
      communication between the embryo and maternal endometrium. There is evidence to
      suggest that cytokines produced by the maternal endometrium and the developing
      embryo play a crucial role in this signalling process. Although numerous cytokine
      receptor pairs are expressed by the maternal endometrium and the embryo during
      implantation, functional knowledge of these cytokines is limited. Compelling data
      demonstrating a functional role for cytokines in implantation comes from studies
      using specific cytokine and cytokine receptor knockout mice. There are limited
      similar data for human implantation, but clinical correlative data and studies
      using in vitro models indicate that cytokines may have an important functional
      role in this process. Cytokines that appear to have a functional role in
      mammalian implantation include leukaemia inhibitory factor, interleukin 1,
      hepatocyte growth factor, stem cell factor, macrophage colony-stimulating factor
      and insulin-like growth factors. As implantation failure is a significant cause
      of natural and in vitro fertilization pregnancy failure, a better understanding
      of the functional role of these cytokine-receptor pairs is important for
      improving the diagnosis and treatment of infertility.

PMID- 10889833
TI  - Embryonic regulation of endometrial molecules in human implantation.
AB  - Embryonic implantation requires co-ordinated development of the blastocyst and
      the maternal endometrium. Considerable advances have been made in understanding
      the cell biology of these partner tissues separately. Nevertheless, communication
      between these tissues and the reciprocal effects of these tissues on each other
      constitutes an exciting and as yet unsolved paradigm in reproductive medicine.
      Crosstalk between the embryo, endometrium and the corpus luteum is known to occur
      in ruminants and primates, and, more specifically, endometrial-embryonic
      interactions are reported in rodents and primates. In this review, an in vitro
      model for analysing the interactions between human endometrial epithelium and
      blastocyst in the adhesion phase of embryonic implantation is presented. The
      results of investigations of embryonic regulation of endometrial epithelial
      molecules such as adhesion molecules, mucins, chemokines and cytoskeleton
      proteins are also presented.

PMID- 10889834
TI  - Tissue interactions in the control of trophoblast invasion.
AB  - On the basis of observations made in an explant model of anchoring villus
      development, it is proposed that two discrete types of signal are required to
      trigger the entry of cytotrophoblast into the migratory extravillous lineage. The
      first is mediated by contact of the tip of the first trimester mesenchymal villus
      with decidual extracellular matrix, in response to which stem villous
      cytotrophoblast undergoes a proliferative burst and differentiates into cells of
      the cytotrophoblast column, anchoring peripheral villi to the uterus. Column
      stability is dependent on the interaction between extracellular fibronectin and
      integrin alpha 5 beta 1 expressed at the cell surface, both of which are
      upregulated in this pathway. Subsequently, cells detach in large numbers from the
      periphery of the column and become migratory infiltrative cells. This step is
      dependent on paracrine signalling from the mesenchymal cells that lie directly
      beneath the villous basement membrane. As the signal decreases with increasing
      distance from the placental anchoring villus, this mechanism might account for
      the fact that trophoblast invasion progresses no deeper than the inner
      myometrium.

PMID- 10889835
TI  - Mechanisms of endometrial control of trophoblast invasion.
AB  - Tumour invasion and trophoblastic invasion share the same biochemical mediators:
      the matrix metalloproteinases (MMPs) and their inhibitors. MMPs are a family of
      enzymes capable of digesting the extracellular matrices of the host tissues.
      Human cytotrophoblastic cells are constitutively invasive and produce MMPs.
      Tissue inhibitors of metalloproteinases inhibit cytotrophoblastic invasion in
      vitro, indicating that MMPs are causally related to trophoblast invasion in the
      endometrium. In contrast to tumour invasion of a host tissue, trophoblastic
      invasion during implantation and placentation is controlled stringently in both
      space and time. The factors responsible for these important regulatory processes
      are unknown but studies in vitro indicate that endometrial cytokines and growth
      factors are possible candidates. Insulin-like growth factor binding protein 1,
      the major secretory product of the decidua, interleukin 1, interleukin 6, leptin
      and tumour necrosis factor alpha, all of endometrial origin, are stimulators of
      MMPs, whereas transforming growth factor beta inhibits the proteolytic activity
      of cytotrophoblastic cells. Unfortunately, the ways in which these individual
      factors interact to regulate trophoblast invasion are far from being understood.

PMID- 10889836
TI  - Upregulation of human cytotrophoblast invasion by hepatocyte growth factor.
AB  - Mesenchymal-epithelial interactions exert powerful influences on tissue
      architecture. At the molecular level, hepatocyte growth factor (HGF; produced by
      mesenchyme) and its c-met tyrosine kinase receptor (expressed on epithelial
      cells) participate in this paracrine dialogue. In the present study, anti-HGF
      immunoreactivity was usually detected in association with the mesenchymal cores
      of chorionic villi in situ, whereas cytotrophoblasts (CTBs) stained for c-met. In
      pre-eclampsia, mesenchymal HGF staining was either very low or was not observed,
      whereas CTB c-met expression was unchanged compared with control samples. These
      findings suggest that faulty signals emanating from the villus mesenchyme may
      contribute to the failure of CTB invasion that is associated with pre-eclampsia.
      In the present study, this hypothesis was tested and it was found that HGF
      treatment stimulates CTB invasion in vitro by four times. These
      immunolocalization and functional data indicate that HGF-c-met interactions play
      a key role in regulating the depth of CTB invasion in normal pregnancy and pre
      eclampsia.

PMID- 10889837
TI  - Immunological aspects of human implantation.
AB  - The immunological relationship between the mammalian fetus and its mother during
      pregnancy has been considered similar to that between a transplanted allograft
      and its recipient. Hence, it has been assumed that implantation of the fetal
      placenta in the uterus would be controlled in a similar way by a maternal immune
      response mediated by T cells recognizing paternally derived alloantigens
      expressed by the placenta. However, recent evidence indicates that implantation
      might involve predominantly a novel allogeneic recognition system based on
      natural killer cells rather than T cells. The cellular and molecular basis of
      this local immune interaction between the fetal placenta and maternal uterus is
      the focus of intense research interest. As aberrant implantation can cause a
      variety of clinical problems including miscarriage, intrauterine growth
      retardation and pre-eclampsia, an understanding of the immunological mechanism by
      which this process is controlled could lead to the development of regimens to
      improve fetal growth and development.

PMID- 10889838
TI  - Maternal immunological aspects of pregnancy success and failure.
AB  - Historically, auto- and alloimmune maternal immunological abnormalities have been
      proposed to account for pregnancy loss. However, most of these immunological
      theories have not fulfilled the criteria for causality. Autoimmunity involving
      antibodies to cardiolipin and possibly phosphatidylserine is the immunological
      factor best associated with recurrent abortion in a condition known as the
      antiphospholipid syndrome, which occurs in < 5% of women undergoing recurrent
      pregnancy losses. Dichotomous T helper cell 1 (Th1) and Th2 cytokine/growth
      factor responses to trophoblast or other antigens are proposed to be involved in
      pregnancy loss and success, respectively. According to this alloimmune theory,
      decidual immune and inflammatory cells secrete predominantly either Th1 or Th2
      cell cytokines in response to the conceptus or other antigens. The Th1 cytokines
      tumour necrosis factor (TNF) and gamma-interferon are reported to affect many
      reproductive processes adversely, and the Th1 initiating cytokine interleukin 12
      has been found in the decidua of aborting women with Th1 immunity to trophoblast.
      TNF polymorphisms or genes in linkage disequilibrium with TNF have also been
      associated with recurrent abortion in women with Th1 immunity to trophoblast.
      Further investigations are needed to define further the immunological mechanisms
      involved in pregnancy loss, so that effective therapies can be designed and
      properly studied.

PMID- 10889839
TI  - Impact of ovarian hyperstimulation on the luteal phase.
AB  - The contemporary approach to ovarian stimulation in IVF treatment results in
      supraphysiological concentrations of progesterone and oestrogen in the luteal
      phase. These sex steroids act directly and indirectly to mature the endometrium,
      thus influencing its receptivity to implantation. The development of endometrial
      receptivity is a complex process that may be altered by inappropriate exposure to
      sex steroids. Alterations in the oestrogen to progesterone ratio, growth factor
      concentrations and cell adhesion molecule profiles may occur after ovarian
      stimulation, potentially affecting the receptivity of the endometrium. Recent
      clinical IVF studies have shown that implantation rates and corpus luteum
      function are influenced by oestrogen concentrations during the early luteal
      phase. Few comparative studies have been performed, but after ovarian stimulation
      there is a reduced implantation rate and a higher pregnancy loss rate before
      pregnancies can be detected clinically compared with natural cycle conceptions.
      Novel approaches to ovarian stimulation aimed at achieving a more physiological
      luteal phase endocrinology are now being developed. Data from a recent pilot
      study by our laboratory, involving minimal ovarian hyperstimulation and no luteal
      phase support, are discussed.

PMID- 10889840
TI  - The pathophysiology of endometriosis-associated infertility: follicular
      environment and embryo quality.
AB  - Several retrospective analyses of IVF and oocyte donation programmes, performed
      to gain clinical knowledge of the factors implicated in the aetiology of
      endometriosis-associated infertility, have demonstrated that the quality of the
      embryo is affected in patients with endometriosis. To understand the mechanisms
      of this alteration, the endocrine, paracrine and autocrine conditions induced
      during folliculogenesis in women with and without endometriosis were
      investigated. The first approach was to study ovarian steroid secretion in women
      undergoing IVF. Progesterone concentrations in follicular fluid increased with
      the severity of the disease and an increase in progesterone accumulation in vitro
      was observed in basal and hCG-stimulated granulosa cell cultures. It is proposed
      that the pattern of progesterone secretion may be related to changes in the
      release of cytokines by ovarian and white blood cells. Hence, a second trial
      measured interleukin 1 (IL-1), IL-6 and vascular endothelial growth factor (VEGF)
      concentrations in serum, follicular fluid and granulosa cell cultures. IL-6
      concentrations in serum were higher in the natural cycles of women with
      endometriosis than in women in the control group, and were modulated by ovarian
      stimulation, decreasing significantly in serum from stimulated cycles. In
      addition, IL-6 concentrations were higher in the follicular fluid of women with
      endometriosis than in those in the control group and IL-6 was released in higher
      amounts by granulosa luteal cells of patients with endometriosis. VEGF was
      accumulated in lower concentrations in the follicular fluid of patients with
      endometriosis. These observations indicate that infertility in patients with
      endometriosis may be related to alterations within the follicle which, in turn,
      result in oocytes and embryos of lower quality, as demonstrated in the IVF
      programme. In addition, these embryos have a reduced ability to implant, as
      observed in the oocyte donation model. These alterations may be induced by
      functional changes in the process of folliculogenesis that affect steroid
      synthesis, as well as by cytokine release by ovarian and blood cells.

PMID- 10889841
TI  - Implantation defect in endometriosis: endometrium or peritoneal fluid.
AB  - Clinical observations indicate that an implantation defect occurs in women with
      endometriosis. Despite intense research, the role of alterations in endometrial
      receptivity and the peritoneal fluid microenvironment in the derangement of
      implantation in endometriosis remains controversial. In this review, the evidence
      for the altered endometrial receptivity and peritoneal environment are
      summarized, and their effects on the implantation defect in women with
      endometriosis are discussed. Recent studies on cell adhesion molecules and their
      ligands, apoptosis, homeobox genes and the direct action of gonadotrophin
      releasing hormone analogues are reviewed with respect to their contribution to
      endometrial receptivity in endometriosis. The possible mechanisms by which an
      altered peritoneal environment of endometriosis may affect implantation,
      including cytokine concentrations, iron metabolism, biochemical factors and
      embryotoxicity are discussed.

PMID- 10889842
TI  - Peri-implantation embryopathy induced by maternal diabetes.
AB  - Almost 10 years ago, it was proposed that the packaging of all devices and
      supplies used by diabetic patients for routine care should carry this warning
      label: 'Poor control of diabetes may cause birth defects. See your physician
      before becoming pregnant'. The present article reviews the evidence supporting
      the hypothesis that in mouse and rat experimental models, maternal pre
      conceptional diabetes induces severe developmental alterations in embryos before
      and at implantation. The review (i) summarizes observations on embryos exposed to
      maternal diabetes in utero, (ii) summarizes data obtained by culturing embryos in
      vitro in the presence of high concentrations of D-glucose, (iii) discusses the
      possibility that alterations in the release of cytokines and growth factors by
      uterine cells contribute to early embryopathy and (iv) summarizes the evidence
      that apoptosis, a process of normal embryonic development, may be disrupted in
      blastocysts exposed to diabetic conditions in vivo and in vitro.

PMID- 10889843
TI  - Is there a place for preimplantation genetic diagnosis screening in recurrent
      miscarriage patients?
AB  - Chromosomal abnormalities are one of the factors known to interfere with normal
      embryo development; thus preimplantation genetic diagnosis (PGD) for chromosome
      anomalies may be a new tool for improving the pregnancy rate in selected groups
      of patients. Embryos from three groups of patients (control, aged and recurrent
      miscarriage patients) were screened by PGD using specific DNA probes for
      chromosomes 13, 16, 18, 21, 22, X and Y. The control and aged groups were
      included in the PGD study because the women carried sex-linked genetic disease.
      The frequencies of chromosome anomalies observed in older women (46.3%) and in
      recurrent miscarriage patients (53%) were significantly higher (P < 0.05) than
      the frequency in the control group (19.3%). After PGD screening and transfer of
      normal embryos, pregnancies were obtained in women who had undergone repeated
      abortions (approximate 25% pregnancy rate per transfer) but not in older women.
      On the basis of these data, it seems that PGD screening of embryos can help some
      women undergoing repeated abortions, as these techniques allow successful
      pregnancies to be obtained or, if no pregnancy can be obtained, the results may
      help the couple to decide whether to enter an embryo or gamete donation
      programme.

PMID- 10889844
TI  - Is there a place for biochemical embryonic preimplantational screening?
AB  - The advent of assisted reproductive techniques such as intracytoplasmic sperm
      injection has markedly reduced the problem of unsuccessful fertilization in
      modern IVF. However, pregnancy rates and 'take-home-baby' rates remain
      unsatisfactorily low. Attempts to overcome low pregnancy rates by transferring a
      larger number of embryos to the mother often result in multiple pregnancies. The
      preimplantation embryo synthesizes several proteins that may signal its presence
      to the maternal system, and the interaction between the embryo and the
      endometrium is controlled, at least in part, by cytokines and growth factors.
      However, little is known about the interactions between the embryonic and
      maternal proteins. A better understanding of normal preimplantation embryo
      development may lead to improved in vitro culture conditions and higher pregnancy
      rates. This review gives an overview of the current knowledge of the embryonic
      factors produced during the preimplantation period. The development of the
      interleukin 1 system for screening human preimplantation embryos is also
      discussed. Current biochemical embryonic screening procedures are highly
      experimental, but increasing knowledge of the physiology of embryonic development
      might enable these screening procedures to be used to identify embryos that are
      capable of successful implantation.

PMID- 10889845
TI  - Genes run in the family.

PMID- 10889846
TI  - Home visits.

PMID- 10889847
TI  - Misconceptions about PWCs.

PMID- 10889848
TI  - Does risk of miscarriage increase?

PMID- 10889849
TI  - Comparing oral analgesia.

PMID- 10889850
TI  - Leaves a bad taste.

PMID- 10889851
TI  - Is testing always necessary?

PMID- 10889852
TI  - Solutions needed to control environmental illness.

PMID- 10889853
TI  - Occupational exposure to mercury. What is a safe level?
AB  - QUESTION: One of my pregnant patients, a dental hygienist, uses mercury in her
      workplace, but appears to have no symptoms of mercury toxicity. She has heard
      that mercury might affect her fetus. What should I recommend to her? What is a
      safe level of mercury in the air for pregnant women? ANSWER: Testing for levels
      of mercury in whole blood and, preferably, urine is useful for confirming
      exposure. Currently, mercury vapour concentrations greater than 0.01 mg/m3 are
      considered unsafe. Also, women of childbearing age should avoid contact with
      mercury salts in the workplace.

PMID- 10889854
TI  - Ophthaproblem. Retinal arterial macroaneurysm.

PMID- 10889855
TI  - Radiology rounds. Molar pregnancy (hydatidiform mole; gestational trophoblastic
      disease).

PMID- 10889856
TI  - Dermacase. Livedo reticularis secondary to lupus erythematosus.

PMID- 10889857
TI  - Helicobacter pylori infection in children.

PMID- 10889858
TI  - Should family physicians be teaching and encouraging women to perform regular
      breast self-examination?

PMID- 10889859
TI  - False-positive results in breast cancer screening.

PMID- 10889860
TI  - Procedural skills training. Canadian family practice residency programs.
AB  - OBJECTIVE: To survey Canadian family practice residency programs to discover
      which procedural skills residents are expected to learn. DESIGN: Cross-sectional
      eight-item questionnaire. SETTING AND PARTICIPANTS: The survey was sent to all 92
      program directors and site or unit directors of family practice residency
      programs across Canada. MAIN OUTCOME MEASURES: Information on procedural skills
      lists was solicited. We sought date of creation, date of most recent revision,
      and who was involved in creating the list. A copy of the most recent list
      available was requested. RESULTS: We received 65 responses, for a 71% return
      rate. Surveys were received from all provinces and from all Canadian universities
      offering family practice residency programs. We received 24 unique lists of
      procedural skills: the shortest listed only 10 procedural skills; the longest, 75
      skills; and the average, 36 skills. Only five procedural skills were found on
      more than 80% of the lists; 30 skills were listed on half or more of the lists.
      CONCLUSIONS: Canadian family practice residency programs have widely varying
      expectations of procedural skills for their residents. This survey is a first
      step in examining the whole issue of procedural skills training in Canadian
      family medicine programs.

PMID- 10889861
TI  - Postgraduate training positions. Follow-up survey of third-year residents in
      family medicine.
AB  - OBJECTIVE: To survey all family medicine programs in Canada to determine how many
      positions for third-year training were available. DESIGN: The survey instrument
      contained questions to determine how many second-year positions and how many
      third-year positions each program had. Descriptions of third-year positions were
      requested. One survey question asked about the percentage of people with third
      year training who initially went into rural or small-town practice. Last, each
      program director was asked for an opinion on how many third-year positions should
      be available for further training. SETTING: The survey was administered to the
      program directors of all 16 family medicine programs in Canada. PARTICIPANTS:
      Program directors of departments of family medicine. RESULTS: The survey
      indicated that the number of third-year positions was 18% of the number of second
      year positions currently available (an increase over the 10% determined in
      Busing's study in 1989). The largest proportion of third-year training was in
      emergency medicine, and approximately 30% of third-year positions were primarily
      reserved for physicians intending to go into rural practice. Academic family
      physicians and residents are in fairly close agreement that third-year positions
      should represent 40% of second-year positions. CONCLUSION: A survey of Canadian
      family medicine programs during the 1996-1997 academic years indicated that third
      year positions available for family medicine residents have almost doubled since
      Busing's original survey in 1989.

PMID- 10889862
TI  - Perceived role of primary care physicians in Nova Scotia's reformed health care
      system. Qualitative study.
AB  - OBJECTIVE: To determine primary care physicians' perceptions of their role in a
      reformed health system. DESIGN: Qualitative study using in-depth interviews.
      SETTING: Province of Nova Scotia. PARTICIPANTS: Purposefully selected sample of
      14 practising primary care physicians. MAIN OUTCOME FINDINGS: Participants
      identified seven aspects of their role: primarily, diagnosis and treatment of
      patient's medical problems; then coordination, counseling, education, advocacy,
      disease prevention, and gatekeeping. The range of activities and degree of
      responsibility assumed by participants, however, varied. Factors affecting role
      perception fell into three categories: philosophical view of health and medicine,
      willingness to collaborate, and practical realities. Participants differed in
      their understanding of primary health care and their overall vision of the health
      system. Remuneration policies and concerns about sharing accountability were
      factors preventing an integrated, collaborative approach to care. Personal,
      patient, and structural realities also limited physicians' roles. CONCLUSIONS:
      This sample of primary care physicians had diverse perceptions of their role.
      Results of this study could provide information for identifying issues that need
      to be addressed to facilitate changes taking place in the health care system.

PMID- 10889863
TI  - Hereditary breast cancer. Risk assessment of patients with a family history of
      breast cancer.
AB  - OBJECTIVES: To assist family physicians in stratifying women with a family
      history of breast cancer as being at low, moderate, or high risk of hereditary
      breast cancer (HBC). To present guidelines for managing each of these risk
      groups. QUALITY OF EVIDENCE: A MEDLINE search was conducted from January 1976 to
      December 1997 using key words related to breast cancer risk factors, risk
      assessment, prevention, and screening. Risk stratification criteria were derived
      empirically and assessed using retrospective chart review. MAIN FINDINGS:
      Although up to 20% of women in the general population have a family history of
      breast cancer, less than 5% are at high risk for HBC. Certain features in a
      family history suggest increased risk. Women with none of these features are at
      low risk for HBC and should have annual clinical breast examinations and
      mammography at least every 2 years starting at age 50. Women with one or more
      features of increased risk who do not meet criteria for referral to a familial
      cancer clinic are at moderate risk for HBC and should begin annual mammography
      and clinical breast examination at age 40. Women who meet referral criteria are
      at high risk for HBC and should be counseled regarding referral to a familial
      cancer clinic for more detailed risk assessment and consideration for genetic
      testing. All women should be taught proper breast self-examination technique and
      encouraged but not pressured to practise it monthly for life. CONCLUSION: A
      simple algorithm can assist physicians in stratifying women into low, moderate,
      and high HBC risk groups. Management strategies for each group are given in this
      article and the two following (Heisey et al page 114 and Carroll et al page 126).

PMID- 10889864
TI  - Hereditary breast cancer. Identifying and managing BRCA1 and BRCA2 carriers.
AB  - OBJECTIVES: To present a strategy for identifying candidates for consideration of
      BRCA1 and BRCA2 mutation testing. To discuss the implications of identifying
      patients as BRCA1 or BRCA2 mutation carriers, and to provide recommendations for
      managing them. QUALITY OF EVIDENCE: A MEDLINE search from January 1990 to May
      1998 was performed using the terms genetic breast screening, BRCA1, and BRCA2.
      The bibliographies of articles found were searched for further relevant titles.
      There are no published, randomized controlled clinical trials of management
      strategies for known BRCA carriers. Many recommendations for management are based
      on expert opinion only. MAIN FINDINGS: About 5% of women with breast cancer are
      carriers of genetic mutations. An accurate and detailed family history is the
      most important tool for identifying potential BRCA1 and BRCA2 mutation carriers.
      Women identified as carriers have a substantially increased risk of breast and
      ovarian cancer. Male carriers have a moderately increased risk of prostate
      cancer. Management strategies for carriers are not well studied but include
      increased surveillance, preventive surgery, chemoprevention, and lifestyle
      modification. CONCLUSION: Family physicians must be able to identify people at
      risk, to discuss management strategies, and when appropriate, to offer referral
      for consideration of genetic testing. There is an urgent need for research to
      determine the effectiveness of surveillance strategies, preventive surgery,
      chemoprevention, and lifestyle modification for BRCA1 and BRCA2 mutation
      carriers.

PMID- 10889866
TI  - Reflecting the extraordinary pace of change. Canadian Immunization Guide.
      Laboratory Centre for Disease Control, Health Protection Branch, Health Canada.

PMID- 10889865
TI  - Hereditary breast cancer. Psychosocial issues and family physicians' role.
AB  - OBJECTIVES: To outline the psychosocial issues in hereditary breast cancer (HBC)
      assessment and discuss the role of family physicians. QUALITY OF EVIDENCE: A
      literature search using MEDLINE, CINAHL, CancerLit, and HealthStar databases was
      conducted from January 1990 to April 1998, using the key words breast cancer or
      neoplasm and familial or hereditary, genetic testing or screening, primary care
      or family physician or counseling, genetic counseling, psychosocial or
      psychological. We found only a few studies focusing on a small number of well
      studied "research families." MAIN FINDINGS: Women with a family history of breast
      cancer were likely to be highly interested in genetic testing for cancer risk.
      The benefit of testing for those with negative results is reassurance. Those
      found to be carriers of genetic mutations might benefit from increased
      surveillance and prophylactic therapy. Risks of testing include anxiety,
      depression, guilt, altered self-image, and insurance and employment
      discrimination. A family physician's role is to assess risk, to provide
      information and support so women can make informed choices about referral to
      familial cancer clinics, to offer cancer surveillance, and to provide support
      once genetic test results are available. CONCLUSION: Genetic testing is rapidly
      moving from research to clinical applications. Family physicians play an integral
      role in educating and managing women at risk for HBC. Physicians must prepare
      themselves with knowledge and counseling skills to meet the challenges of this
      new technology.

PMID- 10889867
TI  - The best way to pay for your children's education. Part 2: Different trust plans.

PMID- 10889868
TI  - The specialty of family medicine.

PMID- 10889869
TI  - Physiology of the endocrine pancreas.
AB  - The endocrine pancreas is composed of nests of cells called the islets of
      Langerhans, which comprise only about 20% of pancreatic cell mass and secrete
      insulin, glucagon, somatostatin, and pancreatic polypeptide. Insulin is anabolic,
      increasing storage of glucose, fatty acids and amino acids, while glucagon namely
      stimulates hepatic glycogenolysis, gluconeogenesis, and ketogenesis. Somatostatin
      acts as a paracrine agent to inhibit both insulin and glucagon release, and,
      therefore, to modulate their output. This article explores factors controlling
      release of these hormones, as well as the way in which they affect fuel
      metabolism in the whole animal.

PMID- 10889870
TI  - Biochemical and physiological manifestations of acute insulin withdrawal.
AB  - When insulin is withdrawn acutely from a severely diabetic patient, a sequence of
      intricately interconnected events begins which, without intervention, can result
      in coma and death. These events involve not only carbohydrate metabolism, but
      protein and lipid metabolism, electrolyte and fluid balance as well. Acute
      insulin withdrawal permits the unopposed action of the counter-regulatory
      hormones (which are attempting to elevate the plasma glucose concentration),
      namely glucagon, cortisol, growth hormone, and epinephrine. This article details
      interrelationships existing between the many biochemical and physiological events
      that are occurring more or less simultaneously in the animal following acute
      insulin withdrawal.

PMID- 10889871
TI  - Currently available insulin preparations for use in the dog and cat.
AB  - Many insulin preparations are available for use in the diabetic dog or cat.
      Appropriate selection of an insulin preparation must take into account several
      factors. These include species of patient, type of diabetes, duration of action
      of insulin, client preferences, and, sometimes, species of origin of the insulin
      preparation.

PMID- 10889872
TI  - Diabetic ketoacidosis.
AB  - Diabetic ketoacidosis (DKA) is a complex and potentially fatal metabolic disorder
      in patients with diabetes mellitus. An understanding of the pathophysiology of
      DKA is essential in order to optimize patient management. A combination of
      insulin deficiency, increased stress hormone levels, and volume depletion account
      for the laboratory abnormalities and clinical signs observed in these patients.
      Successful therapy depends upon correction of hyperglycemia, dehydration, and
      electrolyte and blood gas abnormalities.

PMID- 10889873
TI  - Management of the uncomplicated canine diabetic.
AB  - Managing the uncomplicated canine diabetic may still be a challenging endeavor.
      Client education is the most important treatment to provide. The client must
      understand the technique of drug handling and administration, the importance of
      diet in treating the animal, how to handle an emergency situation, and, most
      importantly, the disease itself. The clinician must realize that although "tight"
      glycemic control is the optimal goal; the reality is often a compromise of mild
      hyperglycemia with resolution of clinical signs. When regulation cannot be
      maintained it is necessary to investigate the causes of insulin resistance.

PMID- 10889874
TI  - Oral hypoglycemic agents for noninsulin-dependent diabetes mellitus in the cat.
AB  - The use of oral hypoglycemic agents for the treatment of noninsulin-dependent
      diabetes mellitus (NIDDM) is still in its infancy. The purpose of this article is
      to summarize the current knowledge regarding the use of oral hypoglycemic agents
      in cats. Oral hypoglycemic therapy is more successful when the veterinarian is
      aware of the mechanism of action of the drug, as well as its dosage, side
      effects, and drug interactions. A short section on combining insulin with oral
      hypoglycemics and monitoring therapy with oral hypoglycemic agents is also
      included.

PMID- 10889875
TI  - Complications and concurrent disease associated with diabetes mellitus.
AB  - Many animals with diabetes mellitus are severely ill on clinical presentation.
      The spectrum of disease is quite variable and includes diabetic ketoacidosis
      (DKA), ketosis without acidosis, hyperosmolar nonketotic syndrome (HNKS), and
      other nonketotic variants (negative urine ketones, serum osmolality < 340 mOsm/kg
      with or without acidosis). These more severe forms of diabetes are often
      precipitated by concurrent diseases such as pyelonephritis, pancreatitis,
      pyometra, hyperadrenocorticism, renal failure, and heart failure. To make matters
      worse, in-hospital treatment of diabetic dogs and cats is commonly associated
      with serious complications, including hypoglycemia, hypokalemia, and
      hypophosphatemia.

PMID- 10889876
TI  - Transplantation for the treatment of diabetes mellitus.
AB  - Pancreas and pancreatic islet cell transplantation have been investigated as
      potential methods of treatment for diabetes mellitus in both man and animals.
      Successful transplantation could ultimately provide a cure for insulin-dependent
      diabetes mellitus. Not only would it greatly improve the quality of life of the
      diabetic patient, but also prevent the multitude of potential complications of
      poor glycemic control. Whole pancreas transplantation has been successful as a
      means of treating diabetes mellitus, however, complications make this treatment
      less than ideal. The focus of diabetes research in many centers worldwide has
      been on successful transplantation of the purified endocrine portion of the
      pancreas. Despite the many years of dedicated research, there remain several
      important obstacles to successful islet cell transplantation in both human and
      veterinary medicine. Currently progress is being made to make islet cell
      transplantation a reality.

PMID- 10889878
TI  - Stereotactic radiosurgery XI. Acoustic neuroma therapy and radiation oncogenesis.

PMID- 10889877
TI  - Diagnosis and treatment of gastrinoma.

PMID- 10889879
TI  - Stereotactic radiosurgery and the risk of haemorrhage from cavernous
      malformations.
AB  - Eighteen patients with cerebral cavernous malformations were treated with single
      dose of cobalt 60 source stereotactic radiosurgery. All had suffered at least one
      haemorrhage prior to treatment with six suffering 2, four suffering 3 and one
      suffering 4. Mean follow-up was 4.5 years. A total of 36 pretreatment
      haemorrhages occurred in 139 patient years. The first haemorrhage each patient
      suffered was taken as the start of observation and not included in the
      rehaemorrhage rate calculation. Three posttreatment haemorrhages occurred in 81
      patient years of observation. The annual haemorrhage rate thus fell from 13%
      before to 3.7% after treatment. The odds ratio was thus 0.29 with a 95%
      confidence interval of (0.08-0.97), but this must be interpreted with caution
      because of the prereferral selection of this group of patients. Three patients
      developed complications of radiosurgery, two of them recovered fully.

PMID- 10889880
TI  - Clinical presentation of a group of NF2 patients to a tertiary referral skull
      base unit.
AB  - The objective of the investigation was to document the clinical presentations of
      a group of patients with neurofibromatosis type two syndrome (NF2), and took the
      form of a retrospective case note review. The investigation took place in the
      tertiary referral skull base unit. The dominant presentation of patients with NF2
      is with auditory/vestibular symptoms (56%), with a smaller proportion of
      presentations being due to non-acoustic intracranial and spinal tumours (44%). At
      the time of presentation the majority of clinically significant tumours could be
      demonstrated in each patient with MRI of the head and spine, with few new tumours
      arising during the subsequent follow-up period. The range of presentation of
      patients with NF2 results in their management being fragmented into a variety of
      clinical setting, diluting the experience amassed in any one centre.

PMID- 10889881
TI  - Outcome from poor grade aneurysmal subarachnoid haemorrhage--which poor grade
      subarachnoid haemorrhage patients benefit from aneurysm clipping?
AB  - Patients with poor grade aneurysmal subarachnoid haemorrhage (SAH) are associated
      with high mortality and morbidity, and hence are often treated conservatively.
      This study has set out to determine the outcome for all poor grade subarachnoid
      haemorrhage patients, and attempts to identify a subgroup with a more favourable
      prognosis. During a prospective audit of patients with aneurysmal SAH, patients
      of poor grade [World Federation of Neurological Surgeons (WFNS) IV (and not
      obeying commands) and V] were sedated, paralysed and ventilated for transfer to
      the Regional Neurosurgical Unit. Any intraventricular blood and/or hydrocephalus
      was treated by external ventricular drainage. Following a 24-h period for active
      blood gas, fluid and electrolyte resuscitation, patients were assessed after
      reversal of sedation. Selection for angiography and potential aneurysm surgery
      was restricted to those who showed a purposeful response to painful stimulation.
      Patients who could readily obey commands were not considered 'true' poor grade
      and were excluded from analysis. In 102 patients with 'true' poor grade SAH
      admitted between 1991 and 1997, the overall management outcome at 6 months was
      poor (favourable outcome 25%, mortality 67%). Following reversal of sedation, 55
      patients demonstrated a purposeful response and proceeded to angiography, of whom
      37 underwent clipping and three coiling of aneurysm. The outcome in this aneurysm
      treated subgroup was favourable in 53% (mortality 28%). If patients over the age
      of 65 years are excluded, the management outcome was favourable in 35% (mortality
      58%), with those patients proceeding to clipping or coiling of aneurysms having a
      favourable outcome in 57% (mortality 27%). Patients over the age of 65 years with
      poor grade SAH had a favourable outcome in only 6% (mortality 85%). The mortality
      for poor grade SAH patients remains high. However, following resuscitation and
      correction of any acute hydrocephalus, a patient subgroup identified on simple
      clinical criteria can be identified who can expect a better outcome.

PMID- 10889883
TI  - A bedside method for investigating the integrity and critical thresholds of
      cerebral pressure autoregulation in severe traumatic brain injury patients.
AB  - To avoid ischaemic secondary insults after severe head injury (SHI) it would be
      helpful to know the relationship between cerebral perfusion pressure (CPP) and
      intracranial pressure (ICP). Static cerebrovascular autoregulation (AR) was
      tested in 14 patients after SHI. Mean arterial pressure (MAP) was varied to
      detect changes in intracranial pressure (ICP) indicative of intact AR. Three
      types of responses were observed: (1) MAP elevation causes an increase in ICP;
      (2) MAP elevation has no or very little effect on ICP; (3) MAP elevation lowers
      ICP; Changes between types 1/2 and type 3 suggests AR breakpoints. Varying
      response types and breakpoints were observed between and within patients. Lower
      AR breakpoints were seen from 60 to 80 mmHg CPP, upper breakpoints were as high
      as 112. CPP monitoring achieves a twofold utility in targeted therapy: (1)
      defining the range of intact AR; and (2) lower AR breakpoint assessment to avoid
      secondary insults. Although the precise relationship between pAR breakpoints and
      the adequacy of cerebral perfusion to meet metabolic needs remains unclear, a
      technique such as described here is simple and has much to offer in targeting
      therapy toward specific pathophysiological processes in traumatic brain injury.

PMID- 10889882
TI  - CT prognostic factors in acute subdural haematomas: the value of the 'worst' CT
      scan.
AB  - The relationship between radiological findings and outcome in patients with acute
      posttraumatic subdural haematomas (SDH) has been based on CT obtained upon
      hospital admission. This study was undertaken to investigate the effects on
      prognosis of SDH patients of lesions not present on admission, but detected by
      subsequent CT. We have also studied those findings present on admission CT that
      could predict worsening of the associated lesions. From 1 May 1989 to 30 April
      1996, we admitted 206 patients harbouring acute SDH of thickness 5 mm or more.
      The admission GCS score ranged from 3 to 15. Each patient underwent CT on
      admission (always within 3 h from injury). Follow-up CT was performed within 12
      24 h after injury and in the following days (an average of 4.3 examinations for
      each patient). These examinations were reviewed by a neuroradiologist and the
      'worst' CT was determined. We defined the 'worst' examination as that showing the
      largest haematoma thickness/midline shift and/or with the most extensive degree
      of parenchymal damage. Clinical factors related to prognosis in this series are
      age, hypoxia/hypotension, GCS motor score and pupillary abnormalities. Time from
      injury to treatment was found relevant only in patients with isolated SDH. CT
      findings on admission that correlated with outcome were haematoma thickness,
      midline shift and status of the basal cisterns. Prognosis was also worsened by
      the presence of associated lesions; SAH alone or associated with brain
      contusions. The last of these was the single most powerful predictor of worse
      outcomes (Odds ratio 0.37, p < 0.004). Whereas the first CT showed parenchymal
      associated damage in 56 patients, the 'worst CT' showed such damage in 105
      patients. Presence of SAH on admission was found significant (p < 0.02) in
      predicting evolving parenchymal damage. Haematoma thickness, midline shift,
      status of the basal cisterns and presence of SAH are related to outcome when
      identified on the initial (early) CT examination. However, early (within 3 h from
      injury) CT under-estimates the ultimate size of parenchymal contusions. Patients
      with SAH on early CT are those at highest risk for associated evolving
      contusions. The use of sequential CT should be included in the routine management
      of head-injured patients.

PMID- 10889884
TI  - Association between arterial and intracranial pressures.
AB  - Fluctuations of arterial blood pressure (ABP) almost always produce a response in
      intracranial pressure (ICP). However, the time-relationship between the ABP and
      ICP waveforms is complex and involves a variety of mechanisms, including those
      responsible for regulation of cerebrovascular tone and venous blood outflow
      through collapsible cortical and bridging veins.

PMID- 10889885
TI  - Neuroendoscopy combined with frameless neuronavigation.
AB  - Minimal invasive neurosurgery is becoming more and more standard in neurosurgical
      procedures. Several types of lesions are now approached endoscopically. The
      surgical planning and intraoperative orientation during endoscopic surgical
      procedures are sometimes difficult. To solve this problem, a combination of the
      endoscopic procedure with a frameless, armless neuronavigation system is used in
      our service. The combination of the endoscope and the frameless navigation system
      was used in tumour surgery, ventriculostomies and arachnoid cyst operations. All
      procedures were performed successfully. The combination of both systems has
      proved to be advantageous because of safe surgical planning using the frameless
      stereotactic technique and the possibility of real time orientation of the
      endoscope. This technique is very useful in removing intraventricular and large
      brain mass lesions.

PMID- 10889886
TI  - A simple technique for neurovascular decompression of the cranial nerves.
AB  - Various synthetic materials and plastic adhesives are used for neurovascular
      decompression, but they may have some adverse effects on nervous tissue. We used
      fibrin glue alone for neurovascular decompression and obtained excellent results
      without complications or recurrence, compared with the previous technique with a
      prosthesis or plastic adhesive.

PMID- 10889887
TI  - Neurocysticercosis: migration and proliferation of cysticercus in a CSF valve.
AB  - A case of colonization of a CSF shunt device by racemous cysts during a long
      lasting course of neurocysticercosis is reported.

PMID- 10889888
TI  - Intracavitary administration of amphotericin B in the treatment of cerebral
      aspergillosis in a non immune-compromised patient: case report and review of the
      literature.
AB  - A 24-year-old man presented with cerebral aspergillus fungal granuloma involving
      the left frontal region secondary to pulmonary aspergillosis. He was otherwise
      healthy with no evidence of immune-suppression. Because of poor penetration of
      amphotericin B into the brain and cerebrospinal fluid (CSF), this patient was
      treated by a combination of systemic and local therapy in addition to surgical
      excision resulting in a cure with follow up for more than three years. This form
      of treatment produced no untoward long-term side effects or neurological sequel.
      On review of the literature on aspergillosis of the central nervous system (CNS),
      we found that six patients, including the present case, have been reported who
      survived longer than 1 year; their treatment included local administration of
      antifungal agent in the abscess cavity or into cerebral ventricles in order to
      control this devastating, treatment-resistant pathological fungal infection.

PMID- 10889889
TI  - Non-convulsive status epilepticus: a treatable cause of confusion in pituitary
      apoplexy.
AB  - Confusion occurring in pituitary apoplexy is well described. We describe a case
      of pituitary apoplexy associated with confusion, occurring as a result of non
      convulsive status epilepticus. Electroencephalography should be performed in
      pituitary apoplexy associated with confusion if this treatable and potentially
      serious complication is not to be missed.

PMID- 10889890
TI  - Primary petrous bone Ewing's sarcoma.
AB  - A case of primary Ewing's sarcoma involving a large portion of the petrous
      temporal bone in an eighteen month old child is reported. The lesion was treated
      by radical surgery and adjuvant chemotherapy and radiotherapy. An extremely rare
      age of presentation, an unusual location and an excellent response to treatment
      are the highlights of this case.

PMID- 10889891
TI  - Disappearance of a basilar tip aneurysm after wrapping.
AB  - A young woman underwent craniotomy and wrapping of a ruptured basilar tip
      aneurysm on day 6 following a subarachnoid hemorrhage. An angiogram 3 years later
      showed that the aneurysm had disappeared. We suggest the possible reasons.

PMID- 10889893
TI  - Extradural haematoma following temporomandibular joint arthrocentesis and lavage.
AB  - We describe a case of a 59-year-old woman who remained drowsy and developed a
      left hemiparesis following right temporomandibular joint (TMJ) arthrocentesis and
      lavage for TMJ dysfunction. CT demonstrated an extradural haematoma. This is the
      first reported case of an extradural haematoma following TMJ arthrocentesis.

PMID- 10889892
TI  - Cavernous malformation of the pineal region: short report and review of the
      literature.
AB  - A case of a cavernous malformation of the pineal region is reported. Unique
      magnetic resonance images of a histologically-verified cavernous malformation of
      the pineal region are presented and the relevant literature on the subject is
      reviewed.

PMID- 10889894
TI  - Symptomatic intraspinal air entrapment.
AB  - A 59-year-old man who had undergone the removal of a lipoma of the thoracic spine
      presented with progressive weakness of the lower limbs when lumbar puncture
      followed drainage of a subcutaneous collection of cerebrospinal fluid. Computed
      tomography showed entrapped intraspinal air which compressed the spinal cord.
      This rare, but serious complication can occur in a patient with altered
      intrathecal pressure following spinal surgery.

PMID- 10889895
TI  - Pituitary metastasis from uterine cervical carcinoma: a case presenting as
      diabetes insipidus.
AB  - The authors report a case of symptomatic pituitary metastasis from an
      adenocarcinoma of the uterine cervix. Only two cases of intrasellar metastasis
      from an adenocarcinoma of the uterine cervix have been previously reported; both
      were identified at autopsy. Our patient presented with clinical features of
      diabetes insipidus and a right sixth nerve palsy. Trans-sphenoidal surgery was
      performed and partial removal of the tumour was achieved. The tumour was an
      epidermoidal carcinoma of the uterine cervix located primarily in the posterior
      lobe of the pituitary. The patient's neurological symptoms were relieved
      following surgery. The possibility of a secondary location must always be
      considered in a differential diagnosis when treating an intrasellar lesion in a
      patient with a documented primary malignancy.

PMID- 10889896
TI  - Transnasal penetrating brain injury with a ball-pen.
AB  - We report a case of a 44-year-old man with 1 day's history of epistaxis. He was
      an in-patient in a psychiatric ward with a history of depression. He had CSF
      rhinorrhoea, was confused and had no focal neurological deficits. A full length
      pencil was removed from his left nostril in the emergency department. CT of the
      brain revealed a tract, but also suggested another foreign body in the inter
      hemispheric space. He had a para-sagittal craniotomy and a 14 cm ball-point pen
      was found lying between the two cerebral hemispheres. This was removed and the
      patient made an uneventful recovery. This is the first report of an attempted
      suicide by transnasal insertion of a ballpoint pen intracranially.

PMID- 10889897
TI  - Window on the ear: Barbara Hepworth and the fenestration series of drawings.
AB  - In November 1943, one of Barbara Hepworth's daughters (Sarah, one of triplets)
      developed osteomyelitis of the thigh. This necessitated operation and subsequent
      treatment at the Princess Elizabeth Orthopaedic Centre in Exeter by Mr. Norman
      Capener. Artist and surgeon subsequently became friends and she encouraged his
      activities as a 'weekend sculptor'. At his invitation she came to the hospital in
      November 1947 watching him in out-patients but more particularly in the operating
      theatre; other visits to London and Exeter followed. These studies of orthopaedic
      procedures form the great majority of Hepworth's sixty-plus hospital
      drawings/paintings but there is also a small group of six paintings involving an
      operation on the ear made in April and May 1948. The link between these two and
      the introduction to the ear surgeon, Mr Garnett Passe, is unclear. Five of the
      paintings of the ear operation are still in circulation but there is also a
      sketchbook containing no fewer than 28 drawings. A selection of the sketches
      together with the fenestration series of paintings will be discussed and also the
      relationship with the surgeon, Mr Garnett Passe.

PMID- 10889898
TI  - The effects of retention intervals on self- and proxy reports of purchases.
AB  - Two studies explored underlying differences between self- and proxy reports and
      determining whether proxy reporters process and retrieve information the same way
      self-reporters do. In both studies, participants recorded their own and a target
      person's incidental purchases for two weeks and then returned, either immediately
      or one-week after the diary-keeping period, for two recall tests. These tests
      pertained to self- and proxy purchases. The reported items were scored against
      the recorded ones. In Study 1, the data indicate that proxies tend to recall more
      typical events than do self-reporters immediately following the diary-keeping
      period. However, after a delay of one week, both proxy and self-reporters tended
      to report typical items. These findings suggest that, at least initially, self-
      and proxy reporters process the information differently but that after one week
      they process it similarly. Study 2 employed a method that was identical to that
      of Study 1 except that participants were given a recognition test. The verbal
      protocols from the recognition test indicate that participants used different
      strategies to determine who made the purchase. Whereas participants focused on
      perceptual details surrounding the event when identifying their own purchases,
      proxies engaged in various strategies to identify their spouses' purchases.

PMID- 10889899
TI  - Phonological similarity and the irrelevant speech effect: implications for models
      of short-term verbal memory.
AB  - Three experiments studied the interaction between irrelevant speech and
      phonological similarity within both the remembered and the irrelevant auditory
      material. Phonological similarity within the remembered list impaired performance
      in both baseline and irrelevant speech conditions, whereas phonological
      similarity between the remembered and ignored irrelevant items did not influence
      performance. Although there was a tendency for similarity within the irrelevant
      items to reduce interference, this proved to be a less robust finding.
      Implications for the theoretical interpretation of the irrelevant speech effect
      are discussed.

PMID- 10889900
TI  - Sharing memories and telling stories: American and Chinese mothers and their 3
      year-olds.
AB  - American and Chinese mothers were asked to talk with their 3-year-old children at
      home about two shared past events and a story (41 mother-child dyads). Results
      revealed between-culture variation in the content and style of mother-child
      conversations when sharing memories and telling stories. American mothers and
      children showed a high-elaborative, independently oriented conversational style
      in which they co-constructed their memories and stories by elaborating on each
      other's responses and focusing on the child's personal predilections and
      opinions. In contrast, Chinese Mother-child dyads employed a low-elaborative,
      interdependently oriented conversational style where mothers frequently posed and
      repeated factual questions and showed great concern with moral rules and
      behavioural standards with their children. Findings suggest that children's early
      social-linguistic environments shape autobiographical remembering and contribute
      to cultural differences in the age and content of earliest childhood memories.

PMID- 10889901
TI  - Working memory: a developmental study of phonological recoding.
AB  - A cross-sectional study using children aged 3 to 7 years and a cross-sequential
      study using children aged between 5 and 8 years showed that the development of
      phonological recoding in working memory was more complex than the simple
      dichotomous picture portrayed in the current literature. It appears that
      initially children use no strategy in recall, which is proposed to represent the
      level of automatic activation of representations in long-term memory and the
      storage capacity of the central executive. This is followed by a period in which
      a visual strategy prevails, followed by a period of dual visual-verbal coding
      before the adult-like strategy of verbal coding finally emerges. The results are
      discussed in terms of three working memory models (Baddeley, 1990; Engle, 1996;
      Logie, 1996) where strategy use is seen as the development of attentional
      processes and phonological recoding as the development of inhibitory mechanisms
      in the central executive to suppress the habitual response set of visual coding.

PMID- 10889902
TI  - Recency and suffix effects with immediate recall of olfactory stimuli.
AB  - In contrast to our understanding of the immediate recall of auditory and visual
      material, little is known about the corresponding characteristics of short-term
      olfactory memory. The current study investigated the pattern of immediate serial
      recall and the associated suffix effect using olfactory stimuli. Subjects were
      trained initially to identify and name correctly nine different odours.
      Experiment 1 established an immediate correct recall span of approximately six
      items. In Experiment 2 participants recalled serially span equivalent lists which
      were followed by a visual, auditory, or olfactory suffix. Primacy was evident in
      the recall curves for all three suffix conditions. Recency, in contrast, was
      evident in the auditory and visual suffix conditions only; there was a strong
      suffix effect in the olfactory suffix condition. Experiment 3 replicated this
      pattern of effects using seven-item lists, and demonstrated that the magnitude of
      the recency and suffix effects obtained in the olfactory modality can equate to
      that obtained in the auditory modality. It is concluded that the pattern of
      recency and suffix effects in the olfactory modality is reliable, and poses
      difficulties for those theories that rely on the presence of a primary linguistic
      code, sound, or changing state as determinants of these effects in serial recall.

PMID- 10889903
TI  - Apoptosis.
AB  - Apoptosis is the genetically regulated form of cell death that permits the safe
      disposal of cells at the point in time when they have fulfilled their intended
      biological function. Examples of apoptosis can be cited throughout the whole of
      the animal and plant kingdoms. It is a vitally important process during normal
      development and the adult life of many living organisms. In humans, dysregulation
      of apoptosis can result in inflammatory, malignant, autoimmune, and
      neurodegenerative diseases. In addition, infectious agents, including viruses,
      exploit cellular apoptosis in the host to evade the immune system. This review
      gives a brief historical perspective of some of the landmark discoveries in
      apoptosis research. The morphological and biochemical stages of apoptosis are
      then covered, followed by an overview of how it can be studied in the laboratory.
      Finally, the implications for therapeutic intervention in disease treatment are
      discussed.

PMID- 10889904
TI  - Laser capture microscopy.
AB  - Human tissues are composed of complex admixtures of different cell types and
      their biologically meaningful analysis necessitates the procurement of pure
      samples of the cells of interest. Many approaches have been used in attempts to
      overcome this difficulty, including a variety of microdissection methods. This
      review concerns a recent advance in microdissection techniques, namely laser
      capture microdissection (LCM). The principle underlying this technique is
      outlined, and practical issues pertaining to LCM are considered. In addition, the
      literature relating to LCM is reviewed, with examples of research applications of
      this technique being outlined.

PMID- 10889905
TI  - Cellular localisation of HHV-8 in Castleman's disease: is there a link with lymph
      node vascularity?
AB  - AIMS: Human herpesvirus 8 (HHV-8) has been identified in multicentric Castleman's
      disease and in angioimmunoblastic lymphadenopathies. However, the presence of the
      virus does not necessarily indicate an aetiological role in these conditions.
      This study investigates the cell types infected by HHV-8 in Castleman's disease
      and examines the correlation between HHV-8 and Castleman's disease lymph node
      angiogenesis. METHODS: Sixteen formalin fixed, paraffin wax embedded samples from
      patients with Castleman's disease (six multicentric, 10 solitary) were examined
      for the presence of HHV-8 using the polymerase chain reaction (PCR), non-isotopic
      in situ hybridisation, PCR in situ hybridisation (PCR-ISH), and real time
      quantitative TaqMan PCR to HHV-8 open reading frame 26 (ORF-26), and viral (v)
      cyclin encoding regions. Vascularity was assessed using CD34, CD31, and factor
      VIII immunocytochemistry, and lymph nodes were scored as "low" or "high".
      RESULTS: Five multicentric Castleman's disease and two solitary Castleman's
      disease biopsies were positive for HHV-8. HHV-8 was identified in approximately
      10% of intranodal B lymphocytes, in endothelial cells, and in subcapsular spindle
      cell proliferations. The copy number of HHV-8 was low at 10-50 copies/1000 cells.
      The highest copy number was in subcapsular spindle cells. There was no
      correlation between vascularity score and HHV-8 status. CONCLUSION: The
      preferential localisation of HHV-8 in subcapsular spindle cell proliferations
      (where early intranodal Kaposi's sarcoma initiates) and endothelial cells in
      Castleman's disease might finally explain the link between intranodal Kaposi's
      sarcoma and Castleman's disease.

PMID- 10889906
TI  - Characterisation of a mouse monoclonal anti-idiotype reactive with a V region
      sequence commonly used by human immunoglobulins.
AB  - BACKGROUND: A mouse monoclonal antibody (2C7/IgG2b kappa) has been described
      recently, which is directed against the major house dust mite allergen Der p 1,
      and whose epitope specificity is representative of a major component of the human
      IgE anti-Der p 1 response. AIMS: To characterise an anti-idiotypic antibody
      (2G10/IgG1 kappa) raised against monoclonal antibody 2C7 as surrogate human IgE
      anti-Der p 1. METHODS: The specificity of the anti-idiotype antibody 2G10 was
      determined by competitive inhibition experiments using human and mouse
      immunoglobulins of known VH gene families. The epitope recognised by monoclonal
      antibody 2G10 was located on the molecular model of the Fv (fragment variable)
      region of monoclonal antibody 2C7. RESULTS: The data suggest that monoclonal
      antibody 2G10 is directed against a crossreactive idiotype on human IgE that is
      shared by polyclonal IgG. Competitive inhibition studies against human
      immunoglobulins, representative of VH2, VH3, and VH4 gene families, showed that
      monoclonal antibody 2G10 is mostly likely to be directed against sequences
      encoded by either VH3 or VH4 genes. The fact that monoclonal antibody 2G10 binds
      to the humanized (complementarity determining region (CDR) grafted) CAMPATH-1H
      antibody, but not to the original rat CAMPATH-1 YTH34.5.6 antibody, indicates
      that it is directed against a framework region rather than the CDRs. Analysis of
      amino acids in the VH region for charge, hydrophobicity, and accessibility
      suggests that reactivity with monoclonal antibody 2G10 is defined by a
      hexapeptide spanning residues 74-79 within framework region 3. CONCLUSION: The
      anti-idiotype monoclonal antibody 2G10 could potentially be used as a probe for
      determining the contribution of the VH3 and VH4 gene segments to antigenic
      specificity.

PMID- 10889907
TI  - Acute lymphoblastic leukaemia: correlation between
      morphological/immunohistochemical and molecular biological findings in bone
      marrow biopsy specimens.
AB  - BACKGROUND: Although numerous antibodies suitable for use on paraffin wax
      embedded sections are available for the subtyping of acute leukaemia (acute
      myelogenous leukaemia (AML) and acute lymphoblastic leukaemia (ALL)) in bone
      marrow biopsy sections, unequivocal identification of the cell line involved is
      sometimes impossible. METHODS: Forty eight formalin fixed, paraffin wax embedded
      bone marrow biopsy specimens that had been decalcified in EDTA were investigated,
      including 42 thought to exhibit ALL on the basis of bone marrow smears. Five
      specimens exhibited AML and one biphenotypic leukaemia, as diagnosed
      immunohistochemically in bone marrow biopsies. Immunostaining was performed with
      antibodies against relatively specific B and T cell antigens. The blasts were
      investigated for rearrangements of the immunoglobulin heavy chain (IgH) and the T
      cell antigen receptor (TCR) genes. RESULTS: Amplifiable DNA was obtained from all
      48 specimens. An IgH gene rearrangement was detected in 20 of 23 c-ALL specimens.
      Four of seven T cell ALL (T-ALL) specimens had a TCR-gamma gene rearrangement,
      and the one B cell ALL (B-ALL) specimen exhibited a clonal IgH gene. Three of
      four cases of unclassifiable ALL could be assigned to the B cell lineage on the
      basis of gene rearrangement analysis. Seven cases originally diagnosed in smears
      as ALL were rediagnosed as AML (n = 5) or biphenotypic leukaemia (n = 2) because
      of immunohistochemical reactivity for myeloperoxidase or lysozyme. Two of these
      AML cases and two of three cases of biphenotypic leukaemia exhibited a monoclonal
      IgH gene rearrangement. CONCLUSIONS: Acute leukaemia can be subtyped in bone
      marrow sections with a limited panel of antibodies suitable for use on paraffin
      wax embedded sections (against CD3, CD10, CD20, CD79a, myeloperoxidase, and
      lysozyme). In patients with ALL and a diagnostically equivocal immunophenotype,
      gene rearrangement analysis might indicate whether the B or T cell lineage is
      involved.

PMID- 10889908
TI  - Genetic polymorphisms of cytochrome p4502E1 and susceptibility to alcoholic liver
      disease and hepatocellular carcinoma in a white population: a study and
      literature review, including meta-analysis.
AB  - AIMS: To investigate the associations between the Rsa I, Dra I, and Taq I genetic
      polymorphisms of cytochrome p4502E1 and susceptibility to alcoholic liver disease
      or to hepatocellular carcinoma. METHODS: DNA samples isolated from 61 patients
      with alcoholic liver disease, 46 patients with hepatocellular carcinoma, and 375
      healthy controls were subjected to polymerase chain reaction amplification
      followed by digestion with the endonucleases Rsa I, Dra I, or Taq I. Meta
      analysis was performed using data from previous studies of Rsa I polymorphism and
      the risk of alcoholic liver disease. RESULTS: No association was found between
      any of the three polymorphisms and susceptibility to hepatocellular carcinoma.
      The distributions of Rsa I and Dra I alleles among the patients with alcoholic
      liver disease were not significantly different from those among the control
      group. Meta-analysis of this data and previous data concerning Rsa I polymorphism
      and alcoholic liver disease risk failed to demonstrate any significant
      association between the two. However, the alcoholic liver disease group in this
      study showed a significantly lower frequency of the less common Taq I allele
      compared with the healthy control group (odds ratio, 0.33; 95% confidence
      interval, 0.12 to 0.78). CONCLUSIONS: Possession of the less common Taq I
      cytochrome p4502E1 allele is associated with reduced susceptibility to alcoholic
      liver disease. There is no existing evidence that the Taq I polymorphism is
      directly associated with altered alcohol metabolism, but it might be in linkage
      disequilibrium with as yet unidentified protective factors.

PMID- 10889909
TI  - Identification of different Borrelia burgdorferi genomic groups from Scottish
      ticks.
AB  - AIM: To characterise 12 Borrelia burgdorferi sensu lato isolates cultured from
      ticks collected in the Highlands of Scotland. METHODS: Three molecular methods
      were used: an outer surface membrane protein A (OSP A) gene polymerase chain
      reaction (PCR) designed to give different molecular weight products with
      different genomic groups, randomly amplified polymorphic DNA (RAPD) analysis, and
      ribosomal RNA (rRNA) gene PCRs using genomic group specific primers. RESULTS: All
      of the molecular methods used were quick and easy to perform and capable of
      differentiating between the different genomic groups of B burgdorferi sensu lato.
      All 12 tick isolates were characterised successfully with each method: five were
      characterised as B afzelii and seven were characterised as B burgdorferi sensu
      stricto. RAPD also identified differences within these genomic groups.
      CONCLUSIONS: From this study, it is now known that at least two different B
      burgdorferi sensu lato genomic groups are present in the Highlands of Scotland: B
      afzelii and B burgdorferi sensu stricto. This information can now be used to
      develop appropriate serological tests, which should improve the diagnosis and
      management of patients with Lyme disease in Scotland. The molecular methods
      chosen were found to be useful typing tools and will allow rapid identification
      of any future isolates.

PMID- 10889910
TI  - Proteolysis in human breast cancer.
AB  - BACKGROUND: The process of proteolysis is important at several stages of the
      metastatic cascade. A balance between the expression of the genes encoding
      endogenous proteinases and inhibitors exists and when the production of
      proteinases exceeds that of inhibitors proteolysis occurs. AIMS: To determine
      whether differences in the profile and activity of proteinases and inhibitors
      exist within breast tumour tissue (n = 51), surrounding background breast tissue
      (n = 43), normal breast tissue from breast reduction mammoplasty operations (n =
      10), and cells of the breast cancer cell line, MCF-7. METHODS: Proteinase (matrix
      metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-9, urokinase-type plasminogen
      activator (uPA), and tissue-type PA (tPA)) and inhibitor (tissue inhibitor of
      metalloproteinases; TIMP-1 and TIMP-2) expression and proteinase activity were
      compared using substrate zymography, western blotting, immunohistochemistry, and
      quenched fluorescent substrate hydrolysis. RESULTS: The presence of all
      proteinases and inhibitors was greater in breast tumour tissue when compared with
      all other types of breast tissue (p < 0.05). The activity of total MMPs as
      determined by quenched fluorescent substrate hydrolysis was also greater in
      breast tumours (p < 0.05). CONCLUSIONS: There is increased proteolysis in human
      breast tumours when compared with other breast tissues.

PMID- 10889911
TI  - Detection of SYT-SSX fusion transcripts in both epithelial and spindle cell areas
      of biphasic synovial sarcoma using laser capture microdissection.
AB  - To investigate the distribution of tumour cells expressing the SYT-SSX fusion
      gene in biphasic synovial sarcoma, modified reverse transcription polymerase
      chain reaction (RT-PCR) analysis was performed using microdissected specimens
      from haematoxylin and eosin stained sections of archival paraffin wax embedded
      tissues. This modified RT-PCR included a stage with degenerate oligonucleotide
      primed (DOP) PCR, which randomly amplified cDNA after reverse transcription. SYT
      SSX fusion transcripts were detected in both epithelial and spindle cell areas of
      all three biphasic synovial sarcomas examined. Subsequent sequence analysis
      confirmed that the detected messages were derived from the SYT-SSX1 fusion gene
      in two cases and from SYT-SSX2 in one. These results indicate that SYT-SSX fusion
      transcripts are found in both epithelial and spindle cell areas of biphasic
      synovial sarcoma, and RT-DOP-PCR-PCR analysis is a useful method for detection of
      extremely small amounts of mRNA in microdissected samples from archival formalin
      fixed, paraffin wax embedded tumour tissues.

PMID- 10889912
TI  - Oral cancer research in the new millennium.

PMID- 10889913
TI  - Genome-wide analysis of oral cancer--early results from the Cancer Genome Anatomy
      Project.
AB  - The Cancer Genome Anatomy Project (CGAP) is a large cooperative effort sponsored
      by the US National Institutes of Health designed to find, catalog and annotate
      genes that are expressed during cancer development. In the past 2 years, the CGAP
      has sequenced over 700,000 clones from approximately 140 cDNA libraries,
      resulting in the identification of over 30,000 new human genes. As a first step
      in applying this project to oral cancer we entered four cell lines--two from oral
      cancer, one from primary oral keratinocytes, and one from oral keratinocytes
      which had been immortalized by human papillomavirus. Libraries of cDNA were made
      and sequenced and the data were deposited in GenBank. The expressed genes were
      then identified where possible. The cell lines, and the total number of expressed
      genes that were cloned from each were: HN3 (oral cancer), 263 genes; HN4 (oral
      cancer), 550 genes; HN5 (primary keratinocytes), 237 genes; HN6 (immortalized
      keratinocytes), 408 genes. The total number of different genes that were found
      was 1160. A total of 38 new genes, of unknown function, were discovered. The data
      presented here represent a beginning of the application of the CGAP technology to
      oral cancer. Even though the data are still quite incomplete, they already
      represent a large quantity of new information and clones of potential utility to
      the oral cancer community, and provide a glimpse of the data sets to be
      forthcoming from the Project. It must therefore be expected that there will soon
      be a large expansion in the volume of data regarding the genetics of oral cancer.
      Those who study this disease must be prepared to develop new methods of analysis
      and storage for handling the oncoming volumes of information.

PMID- 10889914
TI  - Calcifying epithelial odontogenic tumour: biological profile based on 181 cases
      from the literature.
AB  - The present profile of the calcifying epithelial odontogenic tumour (CEOT) is
      based on a literature survey of 181 published tumour cases. The CEOT is a benign,
      though occasional locally invasive, slow-growing neoplasm occurring as
      intraosseous (94%) and extraosseous (6%) variants. The intraosseous type appears
      radiographically as an irregular, uni- or multilocular radiolucent area
      containing radiopaque masses which increases in size and opacity with time. Some
      60% of intraosseous CEOT are associated with an unerupted tooth (or odontoma).
      CEOT shows a relative frequency of 1-2%. The extraosseous variant is diagnosed
      slightly earlier (mean age 34.4 years) than the intraosseous type (mean age 38.9
      years). Both variants have an almost 1:1 gender ratio. The intraosseous CEOT
      shows a maxilla:mandible site ratio of 1:2 and are mainly located in the
      premolar/molar region. The present authors present evidence that the CEOT
      originates from the complex system of dental laminae or remnants thereof.
      Histologically, the CEOT is characterized by the occurrence of sheets, nests and
      masses of polyhedral, eosinophilic epithelial cells which may show cellular
      abnormalities including giant cell formation and nuclear pleomorphism. Some cells
      increase in size and produce a homogeneous, eosinophilic, 'amyloid-like'
      substance which may become calcified and which may be liberated as the cells
      break down. The true nature of the amyloid-like material is still unresolved.
      Histological variants including CEOT with cementum-like components, clear-cell
      CEOT (15 cases reported so far), CEOT-containing Langerhans' cells, combined
      epithelial odontogenic tumour (CEOT/AOT) and CEOT with myoepithelial cells are
      discussed in detail. In view of the relatively indolent biological behaviour of
      the CEOT, mutilating procedures, such as wide resection or hemisection of the
      mandible, seem unwarranted. Enucleation with a margin of macroscopically normal
      tissue is, therefore, the recommended treatment for CEOT involving the mandible.
      Maxillary CEOT should, however, be treated more aggressively, as they tend to
      grow more rapidly and do not usually remain well confined. Generally, recurrences
      are rare. Five years is considered the absolute minimum follow-up period. The
      survey has revealed only one well-documented case of a mandibular CEOT in a 75
      year-old man showing features of malignancy.

PMID- 10889915
TI  - Craniofacial osseous and chondromatous sarcomas in British Columbia--a review of
      34 cases.
AB  - Head and neck sarcomas are very rare diseases. The aim of this study was to
      assess the prevalence and presentation of hard tissue sarcomas in the head and
      neck and jaws. A search of the British Columbia Tumor Registry identified 34
      craniofacial hard tissue sarcomas (11 chondrosarcomas, 23 osteosarcomas) over a
      period of 29 years. A male predominance (1.8:1) and a mean age of 40.4 years at
      diagnosis were seen. Of the 23 patients with osteosarcoma, one-third survived for
      5 years and 12 (52%) died within a mean of 20 months. Of the 11 patients with
      chondrosarcoma, 45% survived for 5 years and two (18%) of the patients died
      within a mean of 6 months. In nine of the osteosarcoma patients (39%) the jaws
      were involved, and in six of those cases (67%) there was mandibular involvement.
      Swelling was the first sign in all jaw patients, with a mean age of 41.1 years at
      diagnosis and a male predominance with a ratio of 8:1. Three of the eight male
      patients with osteosarcoma of the jaw (38%) died within a mean of less than 1
      year. Improved prognosis is related to early recognition and diagnosis to allow
      for adequate surgical resection. The benefit of a combination of surgery with
      irradiation or chemotherapy continues to be investigated.

PMID- 10889916
TI  - Inhibition of microflora associated with oral malignancy.
AB  - Changes in the microflora on oral carcinoma surfaces may lead to both local and
      systemic infections, which may complicate the morbidity of the patient suffering
      from oral malignant neoplasms. Thus, anticancer therapy, irradiation,
      chemotherapy or surgery impairs the defence mechanism of the oral mucosa and is
      accompanied by proliferation of the mucosal biofilm with overgrowth of yeast and
      bacteria. This study investigates the inhibition of the biofilm present on the
      surface of oral squamous cell carcinomas. Biofilm samples were obtained from the
      central surface (1 cm2) of each lesion in 10 patients (eight male, two female;
      mean age: 47.6 years; SD +/- 7.6) before any antibiotherapy or tumour treatment.
      Patients were randomly divided into two groups and were rinsed with Meridol
      mouthrinse (amine fluoride) or placebo (saline solution) for 7 days. Samples were
      repeatedly taken from the same site after rinsing. Samples were transported in
      pre-reduced brain heart infusion broth and cultured within 1 h of removal, using
      aerobic and anaerobic complete and selective media. Total aerobic and anaerobic
      counts were determined and isolated bacteria were identified. The median counts
      of colony forming units (CFU/ml) after rinsing with Meridol were significantly
      lower for both aerobes and anaerobes than before rinsing with Meridol. (For
      aerobes before rinsing: 1.35 x 10(6), after rinsing: 7.55 x 10(5); p = 0.025; for
      anaerobes before rinsing: 1.39 x 10(6), after rinsing: 7.15 x 10(5); p = 0.011.
      Rinsing with placebo: no significant difference was found. Aerobe median counts
      before rinsing: 1.17 x 10(6), after rinsing: 1.03 x 10(5), and for anaerobes:
      before rinsing 1.75 x 10(6), after rinsing: 1.51 x 10(6); p > 0.05 [Wilcoxon
      test].) It was concluded that 7-days (three times a day) Meridol rinsing
      significantly reduced the surface biofilm of oral carcinoma compared to rinsing
      with placebo. Clinical examination indicated no irritation of the mucosa. The
      mouthrinse was well tolerated by the patients, who commented on a reduction in
      burning sensation and bad breath. Besides routine oral hygiene, rinsing itself
      could reduce patient morbidity. The findings of the present study indicate that
      in addition to any other oral focus, the lesion itself, when ulcerated, should
      receive direct antimicrobial treatment so as to reduce patient morbidity and
      enhance quality of life.

PMID- 10889917
TI  - Response of human oral epithelial cells to oxidative damage and the effect of
      vitamin E.
AB  - Smoking and periodontal inflammation are various conditions with the potential to
      induce oxidative stress and thus DNA damage in the oral cavity. In cellular
      defense systems, vitamin E is considered the most powerful lipid-soluble
      antioxidant. To investigate whether oxygen-free radicals alter normal progression
      of the cell cycle and whether vitamin E prevents this damage, we exposed cultured
      normal human oral epithelial cells to hydrogen peroxide (H2O2) in the presence or
      absence of vitamin E. Two primary cell lines were analyzed for the presence of
      hydroxyl radical, cell cycle distribution and morphology. Each cell line received
      five treatments: control, ethanol only, vitamin E only, H2O2 only or vitamin E
      followed by H2O2. Degradation of hydroxyl radicals was detected by electron
      paramagnetic resonance analysis, cell cycle by flow cytometry and morphology by
      organotypic technique. Hydroxyl radicals were generated in H2O2-treated cells at
      an initial concentration, which decreased over a period of time. Cell cycle
      analysis showed that H2O2-treated cells differed from normal cells in that the
      percentage of cells in the G1 phase decreased markedly (34.3 vs. 61.2% in
      control) and the S phase increased (35.5 vs. 15.6% in control). Organotypic
      cultures treated with H2O2 demonstrated nuclear hyperchromatism, loss of
      maturation and prominent nucleoli, features consistent with premalignant
      epithelial transformation. In conclusion, our data suggest that H2O2 produced
      hydroxyl radicals and altered the cell cycle. Also, vitamin E may have the
      potential to reduce oxidative damage caused by hydroxyl radicals.

PMID- 10889918
TI  - Aldehyde dehydrogenase 2 and glutathione S-transferase M 1 polymorphisms in
      relation to the risk for oral cancer in Japanese drinkers.
AB  - We investigated 191 patients with oral cancer (121 males and 70 females) and 121
      non oral cancer patients (69 males and 52 females), both groups with a history of
      alcohol use. Blood was analyzed with aldehyde dehydrogenase 2 (ALDH 2) and
      glutathione S-transferase M 1 (GSTM 1) genotyping. ALDH 2 genotyping was
      performed by polymerase chain reaction (PCR)-Restriction fragment length
      polymorphism (RFLP) method and GSTM 1 genotyping was amplified with PCR using
      GSTM 1 specific primers. In the oral cancer group, the alcohol-drinking rate
      (59.7%) was significantly higher than in the non cancer group (alcohol-drinking
      rate 27.3%, p < 0.01). The incidence of inactive ALDH 2 and GSTM 1 in the cancer
      group with an alcohol-drinking habit was 34.2 and 67.5% and was higher than in
      the non cancer group with an alcohol-drinking habit (15.1, 45.5%).

PMID- 10889919
TI  - Tomatoes, tomato-rich foods, lycopene and cancer of the upper aerodigestive
      tract: a case-control in Uruguay.
AB  - In order to study the relationship between tomatoes, tomato products, lycopene
      and cancers of the upper aerodigestive tract (UADC; oral cavity, pharynx, larynx,
      esophagus) a case-control study was carried out in Uruguay, in the time period
      1996-98. Two-hundred and thirty eight cases and 491 hospitalized controls were
      frequency matched on age, sex, residence and urban/rural status. Both series were
      submitted to a detailed questionnaire, including tobacco smoking, alcohol
      drinking and queries on 64 food items. These data were analyzed by unconditional
      logistic regression, after adjusting by total energy intake. Tomato intake was
      associated with a reduction in risk of 0.30 (95% confidence interval [CI], 0.18
      0.51), whereas tomato sauce-rich foods displayed a protective effect of 0.57 (95%
      CI, 0.33-0.96 for the highest quartile of intake). The food group composed of raw
      tomato and tomato-rich foods showed a strong inverse association with UADC (odds
      ratio [OR], 0.23; 95% CI, 0.13-0.39 for the highest quartile of intake). Lycopene
      was also strongly associated with a reduced risk of 0.22 (95% CI, 0.13-0.37).
      Adjustment of tomato intake for several phytochemicals explained almost
      completely its protective effect, which disappears in this model. Finally, the
      joint effect of lycopene and total phytosterols was associated with a significant
      reduction in risk (OR, 0.11; 95% CI, 0.05-0.23).

PMID- 10889920
TI  - Influence of p53 and bcl-2 on proliferative activity and treatment outcome in
      head and neck cancer patients.
AB  - Knowledge about the influence of biomarkers on cell proliferative activity might
      explain differences in radiosensitivity between head and neck tumors and might
      improve patient selection for the most optimal treatment strategy. p53 and bcl-2
      protein expression were determined immunohistochemically in 56 head and neck
      cancer patients, treated by surgery only in five cases and by radiotherapy, with
      or without surgery, in 51 cases. Relationships with various cell proliferation
      markers, determined by flow-cytometry (G1-phase fraction, S-phase fraction,
      BrdUrd-labeling index, duration of S-phase and potential doubling time) were
      investigated. Associations between these cell proliferation parameters, on the
      one hand, and both p53 and bcl-2, on the other, were not found. Furthermore, p53
      and bcl-2 expression were both not related to clinicopathological parameters (T-
      and N-stage, site, grade) and did not affect loco-regional recurrence-free
      survival and/or disease-free survival. We could not find a prognostic value for
      both p53 and bcl-2 protein expression to differentiate radiosensitive from
      radioresistant head and neck tumors.

PMID- 10889921
TI  - Head and neck squamous cell carcinoma lines produce biologically active
      angiogenic factors.
AB  - Angiogenesis is the formation of capillaries from pre-existing blood vessels.
      Angiogenesis occurs in many developmental, physiologic, and pathologic processes
      including tumor growth. Previous studies have shown that angiogenesis is required
      for growth and metastasis of solid tumors. Fibroblast growth factors (FGF-1, -2)
      and vascular endothelial growth factor (VEGF) are extremely potent angiogenesis
      inducers by stimulating the proliferation and migration of capillary endothelial
      cells. Expression of these factors is upregulated in many solid tumors and
      correlates with high vascularity, lymph node metastasis, and poor clinical
      prognosis. Few studies have examined whether established head and neck squamous
      cell carcinoma (SCC) lines produce biologically active angiogenic factors. By
      immunoprecipitation, we detected FGF and VEGF proteins in cellular lysates of SCC
      lines. We also detected FGF-1 and -2 proteins in serum-free-conditioned medium
      from these lines. Conditioned medium from SCC lines significantly increased
      proliferation of human umbilical vein endothelial cells (HUVEC). This increased
      proliferation was abrogated by pre-incubation of conditioned medium with
      neutralizing antibodies to FGFs and VEGF. Conditioned medium from SCC lines also
      significantly stimulated HUVEC invasion across a reconstituted basement membrane.
      We concluded that head and neck SCC lines secrete biologically active angiogenic
      factors.

PMID- 10889922
TI  - Immunohistochemical Mdm2 expression in minor salivary gland tumours and its
      relationship to p53 gene status.
AB  - Mdm2 protein is a cellular regulator of p53 protein activity. Minor salivary
      gland tumours were investigated for immunohistochemical expression of Mdm2
      protein and for p53 gene status. Formalin-fixed sections were submitted to
      monoclonal antibody anti-Mdm2 through use of the streptavidin-biotin method.
      Nuclear immunoreactivity was scored 1 (0-25% nuclei positive), 2 (26-50%), 3 (51
      75%) and 4 (> 75%). The scores found were: PLGA = 1-4; ACC = 3 and 4; ACA = 2 and
      4; PA = 3. Genomic DNA of p53 gene exons 5-8 was examined by polymerase chain
      reaction and no alterations were detected. The strong immunohistochemical Mdm2
      expression may represent an alternative mechanism to the development of salivary
      gland tumours.

PMID- 10889923
TI  - Isolation and characterisation of adenoid squamous carcinoma cells highly
      producing SCC antigen and CEA from carcinoma of the maxillary sinus.
AB  - A serially transplantable adenoid squamous carcinoma tumour line (SCCMM) derived
      from carcinoma of the maxillary sinus of a 56-year-old male with high serum
      levels of SCC antigen (SCC-Ag) and carcinoembryonic antigen (CEA) was established
      in athymic nude mice. Nude mouse tumours produced by transplantation of operated
      material showed similar histological features to those of the original tumour and
      expression of SCC-Ag and CEA immunohistochemically. In addition, SCC-Ag and CEA
      in sera of tumour-bearing nude mice were detected at high levels in proportion to
      the relative tumour weight. The primary cultured tumour cells demonstrated the
      expression of SCC-Ag and CEA and the production of these antigens into culture
      medium. The serum levels of these tumour antigens were decreased concomitant with
      tumour regression by antitumour drug administration. Therefore, this tumour line
      and its cultured cells could provide a useful model for investigation of the
      relationship between tumour growth and expression of these tumour antigens.

PMID- 10889924
TI  - ras gene mutations in oral cancer in eastern India.
AB  - Oral tumor specimens (n = 50) from eastern Indian population were studied for the
      presence of mutations in the H-, K- and N-ras genes using selective
      oligodeoxynucleotide hybridization and restriction fragment length polymorphism
      analysis of polymerase chain reaction-amplified products. Mutations in H- and K
      ras genes were observed at a frequency of 28 and 33%, respectively, whereas no N
      ras mutation was noticed.

PMID- 10889925
TI  - Human oral squamous cell carcinoma cell lines promote angiogenesis via expression
      of vascular endothelial growth factor and upregulation of KDR/flk-1 expression in
      endothelial cells.
AB  - Angiogenesis is an important phenomenon for the growth and metastasis of solid
      tumors. The present study examined the characterization of angiogenic factors
      produced by human oral squamous cell carcinoma (oral SCC) cell lines established
      from lymph node metastatic tumors and primary tumor in different patients. The
      conditioned medium of HSC3 with the strongest metastatic ability among the
      examined lines enhanced a tube-forming activity of bovine carotid artery
      endothelial (BAE) cells in collagen gel cultures. The treatment of HSC3 with anti
      vascular endothelial growth factor (VEGF) antibody or anti-basic fibroblast
      growth factor (bFGF) antibody, either alone or in combination, attenuated the
      activity of urokinase-type plasminogen activator (uPA) in the endothelial cells
      stimulated by the conditioned medium of HSC3. In contrast, neither anti
      interleukin-8 (IL-8) antibody nor anti-hepatocyte growth factor (HGF beta)
      antibody affected uPA activity in the endothelial cells. Among these HSC cell
      lines, HSC3 secreted VEGF with the highest (1.92 +/- 0.24 ng/10(6) cells/24 h)
      level and bFGF. The level of bFGF secreted by HSC3 was lower than that secreted
      by BAE cells. Other oral SCC cell lines secreted lower levels of VEGF and
      undetectable levels of bFGF. By reverse transcriptase-polymerase chain reaction
      analysis of mRNA the production of VEGF121, VEGF145, VEGF165, VEGF189, and
      VEGF206 in these cell lines was able to be detected. Moreover, the conditioned
      medium of HSC3 enhanced the tyrosine phosphorylation and expression of kinase
      insert domain-containing receptor (KDR/flk-1) in the endothelial cells. These
      results suggest that oral SCC promotes angiogenesis via expression of VEGF and
      upregulation of their receptor KDR/flk-1 expression in endothelial cells.

PMID- 10889926
TI  - c-Abl expression in oral squamous cell carcinomas.
AB  - c-Abl is proto-oncogene product. c-Abl has roles in signal transduction, cell
      cycle regulation, and inhibition of apoptosis. There are many reports about c-Abl
      function in hematopoietic cells, but few are concerned with solid tumors. In the
      present study, biopsy specimens from 44 patients with oral squamous cell
      carcinomas were subjected to immunohistochemistry, and the expression levels of c
      Abl were correlated with clinicopathological features. Statistical analyses
      revealed that c-Abl expression was significantly associated with T-category (p =
      0.011), sex (p = 0.014), and differentiation (p = 0.007), but no significant
      difference was observed with N-category, age, primary tumor region, or the other
      histological gradings. The low c-Abl expression group included more T4, male, and
      poorly differentiated cases. There was a trend towards longer tendency survival
      in the high expression group, but the difference was not significant. We conclude
      that c-Abl is a good candidate for a tumor-expansion marker.

PMID- 10889927
TI  - Homozygous deletion of the PTEN tumor-suppressor gene is not a feature in oral
      squamous cell carcinoma.
AB  - A recently identified putative tumor-suppressor gene, PTEN, at 10q23 has been
      described as mutated or homozygously deleted in many different human tumors. To
      determine the role of the homozygous deletion of this PTEN gene in oral squamous
      cell carcinoma (OSCC), we screened two cell lines derived from the latter tissue
      and 28 tumor samples from patients with OSCC, using a differential display
      polymerase chain reaction (PCR) system and, direct DNA sequencing methods. All of
      the nine exons of the PTEN could be successfully amplified using DNA from tumor
      tissues and the cell lines using this system. DNA sequencing confirmed the
      accuracy of the PCR procedures. However, none of the samples, either from the
      cancer tissues or from the cell lines, showed homozygous deletion of PTEN. These
      data suggest that homozygous deletion of the PTEN gene is unlikely to be a
      feature of OSCCs.

PMID- 10889928
TI  - Clinical relevance of erbB-1 and -2 oncogenes in oral carcinomas.
AB  - To gain a better understanding of molecular changes in oral squamous cell
      carcinomas, we tested fresh tumour specimens from 110 patients for erbB-1 and -2
      oncogene aberrations using the competitive differential polymerase chain
      reaction. The significance of established tumour characteristics such as TNM
      stage, differentiation and oncogene aberrations for tumour progression were
      analyzed. ErbB-2 amplification with a gene copy number > 1.6 in tumour tissue and
      erbB-1 deletion with a gene copy number < 0.4 in tumour-surrounding mucosa are of
      clinical relevance and indicate an early tumour recurrence or metastasis (p <
      0.05). In T1/T2 tumours an erbB-2 gene dosage study allows differentiation
      between tumours with high or low risk for early progression. In a multivariate
      statistical analysis T stage (p < 0.01) and erbB-2 amplification in tumour
      material (p < 0.05) were independent prognostic variables.

PMID- 10889929
TI  - Comparison of cancers of the oral cavity and pharynx worldwide: etiological
      clues.
AB  - We assessed separate and combined sex-specific incidence rates of oral and
      pharyngeal cancer for 1988-92 and oral/pharyngeal ratios from 49 different cancer
      registries in five continents. Incidence trends over a period of approximately 30
      years were evaluated in 16 long active registries for men and four for women.
      Cancers of the lip, salivary glands, and nasopharynx were excluded. The incidence
      of both oral and pharyngeal cancer among men is highest in northern France,
      southern India, a few areas of central and eastern Europe, and Latin America.
      Among women, the highest incidence is observed in India. Oral/pharyngeal ratio is
      everywhere systematically lower in men compared to women. Recent trends for oral
      cancer are more favourable than those for pharyngeal cancer in developing
      countries. In developed countries, trends in oral cancer appears to be more
      closely correlated to changes in alcohol consumption than those of pharyngeal
      cancer.

PMID- 10889931
TI  - Post-traumatic spindle cell nodule misdiagnosed as a herniation of the buccal fat
      pad.
AB  - We studied a quasi-neoplastic lesion that developed in the oral mucosa
      secondarily to trauma. The female patient, 2 years of age, presented with a
      rapidly growing nodule and the lesion was diagnosed as a herniation of the buccal
      fat pad. Following partial resection, no recurrence was seen. The ulcerated
      polypoid mass was composed of compact spindle-cell proliferation with invasion of
      underlying muscle and fat. Atypical stromal cells were present in the myxoid
      areas. The surface edematous stroma contained abundant granulation tissue-type
      vascularity and a mixed population of chronic inflammatory cells. On
      immunohistochemical study, the spindle cells were consistent with myofibroblasts.
      The morphologic features, proliferating cell type, and benign clinical course are
      identical to the post-operative spindle cell nodules that occur in the
      genitourinary tract.

PMID- 10889930
TI  - Clinical and histopathological evaluation of sucralfate in prevention of oral
      mucositis induced by radiation therapy in patients with head and neck
      malignancies.
AB  - Forty-four patients with head and neck malignancies were included in a
      prospective, randomized, double-blind, placebo-controlled study for evaluation of
      sucralfate in prevention of oral mucositis induced by radiation therapy. Patients
      were randomized to receive oral suspensions of either sucralfate (n = 23) or
      placebo (n = 21) in six daily doses of 1 g. The primary tumors were treated with
      portals covering at least one-third of the oral mucosa to a minimum dose of 60
      Gy. Drug therapy was not associated with significant adverse effects and
      compliance was satisfactory. Daily inspection of the oral mucosa and
      questionnaires for oral mucositis-related items demonstrated reduction in oral
      mucositis scores and oral pain scores and biopsies obtained from the buccal
      mucosa demonstrated reduction in evidence of altered vascular calibration,
      altered vascular permeability and leukocyte emigration with sucralfate. Clinical
      and histopathological demonstration of reduction in oral mucositis with
      sucralfate suggests that sucralfate might be recommended in the prevention of
      oral mucositis induced by radiation therapy in patients with head and neck
      malignancies.

PMID- 10889932
TI  - Pulmonary lymphangitic carcinomatosis from an oropharyngeal squamous cell
      carcinoma: a case report.
AB  - Pulmonary lymphangitic carcinomatosis (PLC), a form of lymphatic spread of cancer
      cells, from head and neck cancers is extremely rare. We report here a case of PLC
      from an oropharyngeal squamous cell carcinoma in a 68-year-old man. The patient
      underwent inductive chemoradioimmunotherapy which resulted in complete tumor
      remission. The tumor, however, recurred 6 months later and was resected. Late
      metastasis occurred in the ipsilateral cervical lymph nodes 13 months post
      surgery and these lymph nodes were dissected. Three months later, the patient
      suffered from a fever, cough and dyspnea and a chest radiograph revealed an
      interstitial linear pattern from the right hilum to the right upper lung field.
      Without diagnosis of the pulmonary lesion, swelling of the bilateral lymph nodes
      followed after a few months and dyspnea worsened with spread of the reticular
      shadow and appearance of Kerley's B line on the roentgenogram, suggesting PLC.
      The patient gradually became more distressed and finally died 6 months after the
      onset of dyspnea. The microscopy of the autopsied pulmonary tissue revealed tumor
      cell nests in the lymph vessels in the septa and the pulmonary lesion was
      histopathologically diagnosed as PLC. The present case indicates that we should
      consider PLC when cough and dyspnea with reticular shadows and Kerley's B line
      are observed in patients with head and neck carcinoma.

PMID- 10889933
TI  - Aggressive cemento-ossifying fibroma of the jaws.
AB  - The cemento-ossifying fibroma is probably the most frequent fibro-osseous lesion
      seen by oral pathologists. Occasionally, reports of lesions behaving in an
      aggressive fashion appear in the literature. At the present time, the
      relationship if these "aggressive" lesions to the "usual" fibromas is unclear.
      Two cases of "aggressive" cemento-ossifying fibroma are reported. Certainly,
      clinical, radiological, and histological characteristics of aggressive and usual
      fibromas do coincide. There are, however, diverging features warranting
      separation of different forms. These mild differences may be detected during
      preoperative assessment of the lesion, allowing a diagnosis of aggressive form to
      be made.

PMID- 10889934
TI  - Dentinogenic ghost cell tumor: histologic aspects, immunohistochemistry, lectin
      binding profiles, and biophysical studies.
AB  - Dentinogenic ghost cell tumor accompanied with calcifying odontogenic cyst (COC)
      was described in terms of its clinical, histological, immunohistochemical, lectin
      binding and biophysical properties. The case was a 38-year-old Japanese female,
      in whom the tumor had arisen in the right mandibular premolar and molar region.
      Material obtained by partial mandibulectomy was used. Decalcified paraffin
      sections were used to detect keratins, involucrin, and lectin binding; and non
      decalcified thin sections were used for biophysical analysis. The lesion
      comprising dentinogenic ghost cell tumor and COC contained odontogenic epithelium
      with ghost cells, eosinophilic amorphous materials and osteodentin. Some of the
      eosinophilic material had undergone transformation into osteodentin. Keratins in
      odontogenic epithelia showed positive PKK1 staining in peripheral tumor cells,
      and stainings with KL1 and involucrin were positive in centrally located cells.
      Lectin binding in the amorphous materials was comparatively strong for PNA, and
      SBA, moderate for WGA, RCA-1, and UEA-1, and slight for DBA and ConA. Lectin
      binding affinities were higher in the amorphous materials than in the
      osteodentin. Elemental analysis with an electron probe X-ray microanalysis of the
      amorphous materials and osteodentin showed a pattern similar to that found in the
      normal dentin. The biologic properties of the eosinophilic amorphous materials
      suggested the material to be poorly calcified osteodentin, which gradually
      transformed into the well-calcified type.

PMID- 10889935
TI  - Myofibroma/myofibromatosis is the most common fibrous proliferation of infancy
      and childhood.

PMID- 10889936
TI  - An upright man.

PMID- 10889937
TI  - Visually directed walking to briefly glimpsed targets is not biased toward
      fixation location.
AB  - When observers indicate the magnitude of a previously viewed spatial extent by
      walking without vision to each endpoint, there is little evidence of the
      perceptual collapse in depth associated with some other methods (e.g. visual
      matching). One explanation is that both walking and matching are perceptually
      mediated, but that the perceived layout is task-dependent. In this view,
      perceived depth beyond 2-3 m is typically distorted by an equidistance effect,
      whereby the egocentric distances of nonfixated portions of the depth interval are
      perceptually pulled toward the fixated point. Action-based responses, however,
      recruit processes that enhance perceptual accuracy as the stimulus configuration
      is inspected. This predicts that walked indications of egocentric distance
      performed without vision should exhibit equidistance effects at short exposure
      durations, but become more accurate at longer exposures. In this paper, two
      experiments demonstrate that in a well-lit environment there is substantial
      perceptual anisotropy at near distances (3-5 m), but that walked indications of
      egocentric distance are quite accurate after brief glimpses (150 ms), even when
      the walking target is not directly fixated. Longer exposures do not increase
      accuracy. The results are clearly inconsistent with the task-dependent
      information processing explanation, but do not rule out others in which
      perception mediates both walking and visual matches.

PMID- 10889939
TI  - Category effects on the processing of plane-rotated objects.
AB  - We examined the effects of plane rotations on the identification of exemplars of
      three semantic categories. In the first two experiments line drawings belonging
      to three categories (animals, inanimate objects, and vegetables) were presented
      at four orientations (0 degree, 60 degrees, 120 degrees, and 180 degrees of
      clockwise rotation). The response time was found to depend on stimulus category.
      In particular, whereas rotation effects were shown for animals, no effect at all
      was found for vegetables and only partial effects were found for inanimate
      objects. The unclear pattern found for inanimate objects was further examined in
      experiment 3 where the orientation effects on the identification of two subsets
      of the inanimate category were studied. The hypothesis of view-observation
      frequency was confirmed. In experiment 4, line drawings of objects at different
      orientations were presented in physically degraded versions. The minimum amount
      of visual information necessary to identify rotated stimuli was found to vary as
      a function of stimulus category as well. Results are discussed, combining current
      research on both viewpoint-dependence/independence and neural systems involved in
      category processing.

PMID- 10889938
TI  - The role of iconic memory in change-detection tasks.
AB  - In three experiments, subjects attempted to detect the change of a single item in
      a visually presented array of items. Subjects' ability to detect a change was
      greatly reduced if a blank interstimulus interval (ISI) was inserted between the
      original array and an array in which one item had changed ('change blindness').
      However, change detection improved when the location of the change was cued
      during the blank ISI. This suggests that people represent more information of a
      scene than change blindness might suggest. We test two possible hypotheses why,
      in the absence of a cue, this representation fails to produce good change
      detection. The first claims that the intervening events employed to create change
      blindness result in multiple neural transients which co-occur with the to-be
      detected change. Poor detection rates occur because a serial search of all the
      transient locations is required to detect the change, during which time the
      representation of the original scene fades. The second claims that the occurrence
      of the second frame overwrites the representation of the first frame, unless that
      information is insulated against overwriting by attention. The results support
      the second hypothesis. We conclude that people may have a fairly rich visual
      representation of a scene while the scene is present, but fail to detect changes
      because they lack the ability to simultaneously represent two complete visual
      representations.

PMID- 10889940
TI  - The generic-viewpoint assumption and illusory contours.
AB  - Visual images are ambiguous. Any image, or collection of images, is consistent
      with an infinite number of possible scenes in the world. Yet we are generally
      unaware of this ambiguity. During ordinary perception we are generally aware of
      only one, or perhaps a few of these possibilities. Human vision evidently
      exploits certain constraints--assumptions about the world and images formed of it
      -in order to generate its perceptions. One constraint that has been widely
      studied by researchers in human and machine vision is the generic-viewpoint
      assumption. We show that this assumption can help to explain the widely discussed
      fact that outlines of blobs are ineffective inducers of illusory contours. We
      also present a number of novel effects and report an experiment suggesting that
      the generic-viewpoint assumption strongly influences illusory-contour perception.

PMID- 10889941
TI  - Slope and the Zollner illusion.
AB  - Informal observation suggests that the magnitude of the Zollner illusion is
      reduced when the figure is viewed on a sloping plane. The hypothesis that this
      effect derives from the enlargement of the acute angle of intersection between
      the obliques and the verticals in the figure when it is viewed on a sloping plane
      is here investigated. The magnitude of the Zollner illusion was measured with the
      use of a visual analogue scale. The results show that the change in the magnitude
      of the Zollner effect as a function of the slope of the figure is different from
      that for corresponding figures, with enlarged angles of intersection between the
      obliques and the verticals, presented vertically. It is concluded that the
      enlargement of the angles of intersection can only partly account for the
      reduction of the Zollner effect when the figure is viewed under slope, and that
      some other factor must be involved. An alternative hypothesis is evaluated
      whereby the effects result from the diminution in the contrast of the obliques
      when the figure is viewed under slope. Data are also presented to show that
      observers are able to perceive the enlarged or foreshortened angles of
      intersection veridically.

PMID- 10889942
TI  - Perceptual dimorphism in visual motion from stationary patterns.
AB  - Fraser and Wilcox [1979 Nature (London) 281 565-566] devised a series of complex
      stationary patterns that provoked episodes of compelling illusory motion, but
      only in about two-thirds of people tested. Using simplified versions of their
      stimuli, we have confirmed their claim of perceptual dimorphism. We show that the
      strength of the illusory motion depends upon stimulus duration, eccentricity, and
      contrast. The illusory motion does not require fluctuations in accommodation, as
      has been suggested for some other forms of illusory motion. Finally, we consider
      the relation of Fraser-type motion to other forms of illusory motion.

PMID- 10889943
TI  - Word centre is misperceived.
AB  - Normal readers were asked to mark the middle of visually presented words. They
      made systematic errors toward the left, indicating an overestimation of the
      length of the beginning of a word. The number of characters determines the size
      of this error. The bias extended to pseudowords, letter strings, and symbols, but
      not to blocks, dashes, and lines. Finally, the bias was sensitive to
      typographical errors but not to colour cuing. These findings suggest that special
      cognitive operations determine the perceived spatial extent of words.
      Implications for our understanding of perceptual and cognitive processes in
      reading are discussed.

PMID- 10889944
TI  - Configural processing at birth: evidence for perceptual organisation.
AB  - We report a series of ten experiments aimed to investigate the newborn's ability
      to discriminate the components of a visual pattern and to process the visual
      information that specifies the global configuration of a stimulus. The results
      reveal that: (i) newborn babies are able to distinguish individual elements of a
      stimulus (experiments 1A, 1B, 1C, and 1D); (ii) they can group individual
      elements into a holistic percept on the basis of Gestalt principles (experiments
      2A and 3A); (iii) their spontaneous preferences cannot be easily modified by
      habituation (experiments 2B and 3B); and (iv) when horizontal stimuli are paired
      with vertical stimuli, they prefer the horizontal ones (experiments 4A and 4B).

PMID- 10889945
TI  - In vitro manipulation of nonhuman primate gametes for embryo production and
      embryo transfer.
AB  - Since nonhuman primates are closely related to humans and share many physical
      similarities, they are important for use in research areas such as human
      infectious diseases, reproduction, physiology, endocrinology, metabolism,
      neurology and longevity. To develop and maintain these animals, we must establish
      techniques for in vitro manipulation of spermatozoa and eggs. For a decade my
      research group has been conducting basic research to establish embryo
      manipulation techniques and to clarify the reproductive phenomena in nonhuman
      primates. This article summarizes the past research on in vitro manipulation of
      nonhuman primate gametes, from collection of reproductive cells and in vitro
      fertilization to the birth of offspring after embryo transfer, as well as the
      current status of these research areas. The studies summarized here will directly
      lead to the development of standard techniques for practical and comprehensive
      use in nonhuman primates.

PMID- 10889946
TI  - Characterization of hyperinsulinemic recombinant inbred (RI) strains (SMXA-5 and
      SMXA-9) derived from normoinsulinemic SM/J and A/J mice.
AB  - We discovered two mouse strains (SMXA-5 and SMXA-9) with hyperinsulinemia among
      the substrains and progenitor strains (SM/J and A/J) of the SMXA recombinant
      inbred (RI) strains, and characterized the two strains at 20 weeks of age. SMXA-5
      (mean +/- S.E.M: 9.6 +/- 1.7 ng/ml) and SMXA-9 (7.7 +/- 1.3 ng/ml) males had
      higher serum immunoreactive insulin levels than SM/J (1.4 +/- 0.3 ng/ml) and A/J
      (1.1 +/- 0.1 ng/ml) males in the nonfasting condition. The hypoglycemic response
      to insulin at 30 min after injection was significantly less in SMXA-5 males than
      in SM/J mice. Glucose tolerance test revealed that the incidence of impaired
      glucose tolerant males was 58% (11/19) in SMXA-5 and 42% (10/24) in SMXA-9
      strains, but none in SM/J and A/J strains. SMXA-5 (209 +/- 29 mg/dl) and SMXA-9
      (235 +/- 31 mg/dl) had higher serum triglyceride levels than SM/J (126 +/- 14
      mg/dl) and A/J (89 +/- 5 mg/dl) males in the nonfasting condition. Histologic
      examination revealed enlarged islets in the pancreas of hyperinsulinemic SMXA-5
      male mice. Moreover, SMXA-5 and SMXA-9 mice exhibited mild obesity. SMXA-5 and
      SMXA-9 males were therefore characterized by hyperinsulinemia, impaired glucose
      tolerance, hypertriglyceridemia and mild obesity which resembled some of the
      phenotypes of human Syndrome X, although both progenitor strains were normal so
      far as we examined. Since the RI strains are a powerful tool to facilitate
      polygenic-trait analysis, SMXA-5 and SMXA-9 mice will be useful materials to
      investigate the genetic basis of complex diseases, and are possible new metabolic
      models in relation to hyperinsulinemia.

PMID- 10889947
TI  - Partial hepatectomy of marmoset: clinical and pathological effects and utility in
      microsomal enzyme analysis.
AB  - Liver biopsy based on a partial hepatectomy technique (shearing) was performed in
      10 common marmosets (Callithrix jacchus). This is a preliminary study to evaluate
      the effects of drugs on hepatic microsomal enzymes: cytochrome P-450 and T4
      uridine diphosphate glucuronyl transferase (T4-UDPGT), by comparing post
      treatment values with pre-treatment values individually with a limited number of
      animals. The effects of the biopsy on clinical findings and liver pathology were
      evaluated during the first 5 post-surgical weeks. Although the plasma aspartate
      aminotransferase (AST) activities tended to decrease from 1 to 4 weeks post
      surgery, no abnormality was noted in clinical sign, body weight, the hematocrit
      value or other blood chemical values. At necropsy, adhesion of the sheared site
      of the liver to the parietal peritoneum or the small intestine was evident in 2
      of the 4 marmosets. Microscopic examination revealed focal fibrosis in the liver,
      but it was localized around the sheared site. Based on the above results, it was
      concluded that liver biopsy must be performed more than one month before
      administration of the drug to be tested. The biopsy samples and the whole liver
      samples obtained at autopsy were subjected to analysis of microsomal protein
      content, cytochrome P-450 content and T4-UDPGT activity. In comparison with the
      values from the whole liver samples, those from the biopsy samples showed no
      significant difference. Furthermore, there was a significant correlation rather
      than difference between matched values. This suggested that partial hepatectomy
      is a useful method for obtaining pretreatment values in liver biochemistry to
      evaluate the effects of drug-treatment in individual animals.

PMID- 10889948
TI  - Upgrading of flow cytometric analysis for absolute counts, cytokines and other
      antigenic molecules of cynomolgus monkeys (Macaca fascicularis) by using anti
      human cross-reactive antibodies.
AB  - In order to effectively use cynomolgus monkeys as animal models for human
      diseases, more than 300 anti-human monoclonal antibodies (mAbs) were studied as
      to their cross-reaction with various antigens from cynomolgus monkeys (Macaca
      fascicularis). Two hundred twenty-nine of 339 (67.55%) anti-human mAbs that react
      with human antigens of CD-defined molecules, chemokine receptors, and T cell
      receptors were cross-reactive with the monkey antigens. Using the cross-reactive
      antibodies and the fluorescenced beads for calibration, the procedure for the
      absolute count of monkey lymphocyte subsets was developed and the mean values for
      CD4+ and CD8+ lymphocyte subsets in peripheral blood were 718 and 573/mm3,
      respectively. Moreover, intracellular cytokines, IL-2, IL-4 and IFN gamma, and
      intracellular apoptosis-related proteins, Bcl-2, FADD and active form of caspase
      3 could be detected in peripheral blood mononuclear cells as well as various
      tissue cells. It is therefore practicable to detail the phenotype of leukocytes,
      assess the production of intracellular cytokines and enumerate T-lymphocyte
      subsets by using the cross-reactive human antibodies with respective antigens of
      cynomolgus monkeys.

PMID- 10889950
TI  - An integrated rat genome map based on genetic and cytogenetic data.
AB  - In this study we combined three major rat genome maps, by adding 66 markers to
      the Kyoto Laboratory Animal Science map (KLAS map), and constructed an integrated
      map. The resultant integrated map consists of 5,682 redundant markers, spanning a
      genetic length of 2,028 cM. Eighty genetic markers were anchored to the
      cytogenetic map, fixing all the genetic maps in the physically correct
      orientation. This map encapsulates the progress in rat mapping studies in past
      years and offers useful information for QTL analysis. The map figures are
      available at http:/(/)www.anim.med.kyoto-u.ac.jp/.

PMID- 10889949
TI  - Time-dependent change in baroreflex control capacity of arterial pressure by
      pentobarbital anesthesia in rabbits.
AB  - The present study is designed to investigate the time-dependent effect of
      pentobarbital anesthesia on the baroreflex arterial pressure (AP) control system
      in rabbits. The overall AP control capacity of the baroreflex system was assessed
      with mean arterial pressure (MAP) responses to the rapid mild hemorrhage (2 ml/kg
      body weight) and an overall open-loop gain (G) of the system. The G value was
      determined by means of the following formula: G = delta API/delta APS-1, where
      delta APl is an immediate MAP fall and delta APS a steady-state fall after the
      rapid hemorrhage. Prior to the experiment, two catheters for AP measurement and
      hemorrhage were chronically in-dwelt in the aortic arch via the left subclavian
      and left common carotid arteries, respectively. Control mean arterial pressure
      averaged for 30 sec before the rapid hemorrhage (CMAP), delta API and delta APS
      significantly increased and reached the maximal value at 14 min (CAMP: p < 0.01)
      and 28 min (delta API: p < 0.01 and delta APS: p < 0.01) after the intravenous
      injection of sodium pentobarbital in a 25.0 mg/kg dose, respectively. These
      values gradually decreased in the course of time and tended to recover to near
      the preanesthetic level at 77-98 min after the anesthesia. The G value
      significantly decreased from 7.3 in the conscious state to 1.5 at 28 min after
      the anesthesia (p < 0.001), gradually increased with lapse of time and recovered
      to near the preanesthetic level at 77-98 min after the anesthesia. No significant
      difference in G was observed between in the conscious and anesthetized states
      beyond 70 min after the anesthesia (p > 0.05). These findings suggest that
      pentobarbital sodium exerts a time-dependent inhibitory effect on the baroreflex
      system but does not significantly affect the overall AP control capacity of the
      baroreflex system itself at least 70 min after the intravenous administration at
      a dose of 25.0 mg/kg.

PMID- 10889951
TI  - Cutaneous mastocytomas in Djungarian hamsters.
AB  - Spontaneous cutaneous mastocytomas in Djungarian hamsters (D-hamster) were
      pathologically studied and compared with those in canine and feline cases. Eight
      (9.3%) of 86 cutaneous biopsy cases in D-hamsters were diagnosed as mastocytomas,
      being slightly higher in incidence than in canine and feline species. In 4 of 8 D
      hamster cases, the tumor lesions were in the head and neck in contrast to most
      canine lesions in the extremities. The histopathology of the D-hamster
      mastocytoma was characterized by diffuse or massive proliferation of well
      differentiated tumor cells with severe degeneration of collagen fibers and slight
      eosinophil infiltration in most cases.

PMID- 10889952
TI  - Tss (Tail-short Shionogi), a new short tail mutation found in the BALB/cMs
      strain, maps quite closely to the Tail-short (Ts) locus on mouse chromosome 11.
AB  - A spontaneous morphological mutation characterized by a short and kinky tail
      (Tail-short Shionogi: Tss) was observed in a BALB/cMs mouse breeding colony. The
      inheritance mode of the Tss mutation is semi-dominant, and homozygotes (Tss/Tss)
      are probably embryonic lethal. The viability of the Tss/+ heterozygotes appear to
      be influenced by the mating partner: 47.1% of the (BALB/cMs-Tss/+ x C57BL/6J)F1
      embryos were the mutant phenotype, whereas there were no (BALB/cMs-Tss/+ x A/J)F1
      embryos with the mutant phenotype. The Tss locus was mapped by linkage analysis
      between microsatellite markers D11Mit128 and D11Mit256 on mouse Chromosome 11.
      These results suggest that the Tss mutation is a new allele on the Tail-short
      (Ts) locus.

PMID- 10889953
TI  - Locus of dominant hairless gene (Ht) causing abnormal hair and keratinization
      maps to rat chromosome 10.
AB  - The rat dominant hairless gene (Ht) of the WBN/Ila-Ht rat causes atrichosis in
      Ht/Ht and hypotrichosis in Ht/+. Furthermore the Ht/Ht shows signs of abnormal
      keratinization and almost all of the Ht/Ht die in an immature stage before
      weaning in the conventional environment. Ht/+ was affected by dermatitis caused
      by Staphylococcus aureus, suggesting that the gene Ht might involve defense
      mechanisms against infection. In this study, we performed the linkage analysis of
      the gene Ht by outcross with the Brown Norway rat in the SPF environment. Ninety
      six backcross progeny of (BN x WBN/Ila-Ht/Ht) F1 x WBN/Ila-Ht/Ht were typed with
      microsatellite markers and the gene Ht was mapped on chromosome 10 between Asgr1
      and Nos2 within the map distance of 6.2 cM.

PMID- 10889954
TI  - Differences in survivability among F344 rats.
AB  - Important parameters to identify and develop appropriate animal models for
      longevity science include survivability, age-related disorders, and easy handling
      of aged individuals. It is found that F334/Du and F344/N have distinctive strain
      difference in these parameters. The finding suggests F334/Du and F344/N, even
      though they are historically siblings, need clearly separate identification when
      used as animal models for aging science, in particular, longevity science.

PMID- 10889955
TI  - Comparison of age-related peripheral nerve changes in mice housed in either
      plastic cages with sawdust-covered solid flooring or wire-mesh-floor cages.
AB  - A comparative histologic survey was conducted on the dorsal root, sciatic, tibial
      and medial plantar nerves of 90- and 110-week-old B6C3F1 female mice reared in
      either solid-floor cages covered in sawdust or wire-mesh-floor cages. Age-related
      peripheral nerve lesions, characterized by axonal degeneration and remyelination,
      were present in all nerves surveyed, and were especially prominent in the sciatic
      and medial plantar nerves at 110 weeks of age but, there were no differences
      associated with the type of cage floor in clinical signs, grasping power of the
      fore- and hind-limbs, motor nerve conduction velocity or histopathologic findings
      at these ages.

PMID- 10889956
TI  - Sketch for a metapsychology of affect.
AB  - The author argues that analysing affect, a concept lying on the frontier between
      the mental and the somatic (Freud, 1915a) has to be an embodied pursuit. This
      line of argument finds support in Freud's second hypothesis in 'An Outline of
      Psychoanalysis' (1940), where he writes that psychology should look to the
      somatic processes to see the true essence of what is psychical and in the first
      instance disregard the quality of consciousness. From this baseline the concepts
      of feeling, emotion and affect are differentiated and defined. Feelings and
      emotions are seen as two psychically perceived expressions of affective
      processes. The concept of affect is then defined as an affective matrix linked to
      a predisposition of the bodily systems to react in a certain way to internal or
      external stimuli. The affective matrix can find expression either in psychically
      perceived affects--feelings and emotions--or in physically perceived 'affect
      equivalents'--psychosomatic symptoms and somatic illnesses. It is finally argued
      that this hypothesis finds support in the evolutionary perspective delineated by
      Freud in 'Inhibitions, Symptoms and Anxiety' (1926), where he claims that affects
      are reproductions of very early, perhaps even pre-individual, experiences of
      vital importance.

PMID- 10889957
TI  - Mental pain and the cultural ointment of poetry.
AB  - The author argues that mental pain consists of a wordless sense of self-rupture,
      longing and psychic helplessness that is vague and difficult to convey to others.
      It usually follows the loss of a significant object or its abrupt refusal to meet
      one's anaclitic needs. This results in the laceration of an unconscious, fused
      self-object core of the self. Abruptly precipitated discrepancies between the
      actual and wished-for self-states add to the genesis of mental pain. Issues of
      hatred, guilt, moral masochism as well as fantasies of being beaten can also be
      folded into the experience of mental pain. The feeling is highly disturbing and
      is warded off by psychic retreat, manic defence, induction of pain into others
      and changing the form and function of pain. Each of these can have a pathological
      or healthy outcome depending upon the intrapsychic and social context and upon
      whether they ultimately permit mourning to take place or not. Poetry serves to
      render mental pain bearable by enhancing empathy with one's own repudiated parts.
      With the help of two clinical vignettes, the multi-faceted (defensive, formal and
      content-based) role of poetry in reducing mental pain, enhancing mentalisation of
      its sources and facilitating mourning is discussed. It is suggested that through
      poetry, culture and affect meet and, in this encounter, both are enriched.

PMID- 10889958
TI  - Containment, enactment and communication.
AB  - Two patients are described in whom ordinary means of communication were disrupted
      by the deployment of primitive defensive mechanisms that prevented the author
      from integrating affect, context and counter transference to provide meaningful
      communication of a straight-forward kind. In the first, thinking was fragmented
      and projections into the analyst were difficult to tolerate; in the second, a
      dissociation appeared between affect and language. The author describes how with
      both patients he was led to behave as if he could put right the deficit he
      encountered in their means of communication and how at times he could recognise
      what was happening and interpret the state that the patient was evading, but at
      others was led into enactments that interfered with containment and
      understanding. Nevertheless, these allowed an examination of the type of object
      relations that the patients demanded and believed they needed. The author
      considers that the state of mind this produced in him was partly an evacuation of
      states that the patients could not cope with, but also represented a means of
      enlisting him to carry out functions that they could not or would not tolerate.
      Both patients used the sessions to create a manageable situation that functioned
      as a psychic retreat that he was instrumental in sustaining and that helped them
      avoid contact with reality, impeding their development. However, recognising the
      role he enacted also advanced the understanding of the nature of the retreat and
      of the underlying pathological organisation of the personality.

PMID- 10889959
TI  - Affect, language and communication. 41st IPA Congress plenary session.
AB  - The author discusses Hernandez's enriching and clarifying paper, which directs us
      to the limitations of language with regard to affective movements that barely
      attain the condition of thinkability and thereby to the important and confusing
      topic of enactments, which are the lingua franca for the communication of
      dangerous and repudiated affects. Enactments bridge the interface between what is
      expressible, and inexpressible, between what is forgotten and what is pressing
      for revival, between reality and fantasy and also between one-person and two
      person psychologies. Conceptually the term enactment facilitates the integration
      of the concepts of fantasy, projective identification and countertransference.
      Steiner's richly detailed and moving clinical report demonstrated the value of
      the concept of projective identification for understanding his patient's
      communication of affects. The concept has been neglected until recently by many
      US analysts; one source of confusion has been the assumed reliability of the
      analyst's emotional reactions as an indicator of what the patient is feeling. The
      author asks whether Steiner is speaking loosely or literally when he says that
      his patients put their feelings into him, citing examples to demonstrate that the
      value of the concept of projective identification would be enhanced by a
      clarification of this question.

PMID- 10889960
TI  - Blood and love.
AB  - In this clinical presentation both transgenerationally transmitted and directly
      inflicted trauma are examined as constituents in the psychic life of a gifted
      little girl called Natalia. Her attempts to eroticise and thus modulate those
      aspects of her experience which have deformed her play processes are described
      and the ways in which the analysis served to help her both recognise and regulate
      this material is detailed. The paper is organised around material from the
      opening phase of the work, the play which characterised the middle of the
      analysis and the examination of an essay which the patient wrote in the closing
      phase. The central role of affect for each participant in the analytic work is
      stressed as a pivotal component of the play process.

PMID- 10889961
TI  - Psychoanalytic supervision: the intersubjective development.
AB  - The author argues that an intersubjective perspective on the analytic process
      makes the notion of purely didactic supervision, avoiding countertransference
      issues, untenable and that countertransference is both a clue to the analysand's
      psychic reality and a factor in its evolution. Supervision is seen as a highly
      personal learning process for both supervisor and supervisee and its emotional
      climate as a crucial factor in its evolution into a transitional space,
      generating new meanings. Supervision is portrayed as the crossroads of a matrix
      of object relations of three persons, of a complex network of
      transference/countertransference patterns. The avoidance or denial of the
      supervisor's subjective role in it, maintaining 'a myth of the supervisory
      situation', may make supervision stilted or even oppressive and stand in the way
      of resolving supervisory crises and stalemates. It is argued that several factors
      contribute to the conflictuality of supervision for all partners (often including
      the analysand): the continuous process of mutual evaluation, the reciprocal fears
      of exposing one's weaknesses, the impact of the institute as a setting and the
      transferences it arouses and the inherent conflicts of loyalty for each
      participant in the analytic/supervisory triad. The resulting dynamics and
      relational patterns could become a legitimate and freeing topic in supervisory
      discourse.

PMID- 10889962
TI  - Glycaemic dysregulation and relational/affective dysregulation in a patient with
      diabetes mellitus.
AB  - Recent psychoanalytically inspired psychosomatics conceptualises somatic
      disorders as disorders in the internalised relationship with a regulating object,
      causing physiological/affective dysregulation. In diabetes mellitus, measurements
      of blood glucose allow close monitoring of a form of somatic regulation. Several
      authors have reported parallels between glycaemic oscillations and relational
      vicissitudes, in both experimental and clinical settings. Mothers of diabetic
      patients report a history of misattunement in feeding patterns, while similar
      difficulties, on the symbolic level of accepting mutual communication, are found
      in the analysis of adult patients. More or less conscious opposition to glycaemic
      regulation appears to be linked with problems in distance regulation with the
      object. The author reports a clinical case that gives evidence of this
      parallelism; the patient presents a marked non-integration and dysregulation of
      relational and separateness needs, which both emerge, with respect to the analyst
      and to other objects, in a quickly alternating, violent, juxtaposed fashion
      reminiscent of descriptions of disorganised attachment or of borderline patients.
      These oscillations are closely paralleled by oscillations in glycaemic control,
      where violent withdrawal from relationships corresponds to physiological and
      behavioural disruption of glycaemic regulation patterns. Improved mentalisation
      and integration of the different tendencies in the course of analysis brings to
      both the possibility of stable affective involvement and improvement in diabetic
      control.

PMID- 10889963
TI  - Towards an international dialogue. North American reflections on the Santiago
      Congress.
AB  - In this brief reflection on the Santiago Congress, an attempt is made to clarify
      some of our difficulties in international dialogue. The fantasy persists that
      there is only one psychoanalytic mother tongue; alongside is the wish that
      European, Latin American and North American approaches might be integrated. Is
      such integration possible or desirable? In making clinical observations are we
      all looking at the same phenomena and putting them into different words, or are
      our observations irreconcilable? It is suggested that common ground might exist
      more readily on some levels of abstraction than on others and that North American
      conceptualisations might coexist with European and Latin American
      conceptualisations on separate levels of abstraction. An argument is made for a
      reconsideration of quantitative and energic factors, especially in the realm of
      affect and representation, and a reintegration of such notions into structural
      theory. Because the tight linkage we habitually draw between theory and practice
      may not accurately reflect the analyst's mind at work, we cannot study too
      frequently the details of the clinical hour, including what we observe ourselves
      thinking and doing.

PMID- 10889965
TI  - Affect regulation.

PMID- 10889964
TI  - Affect and development.

PMID- 10889966
TI  - Affect, language and communication: loose ends.

PMID- 10889967
TI  - The search for meaning in the affective expressions of the adolescent patient.

PMID- 10889968
TI  - Darwin revisited: the phylogeny of emotions.

PMID- 10889969
TI  - The countertransference: a Latin American view.

PMID- 10889970
TI  - 'Countertransference: a review of the concept'.

PMID- 10889971
TI  - Memory and therapeutic action.

PMID- 10889972
TI  - Recovery of memories and therapeutic change.

PMID- 10889973
TI  - '"A cure with a defect": a previously unpublished letter by Freud concerning
      "Anna O."'.

PMID- 10889974
TI  - In response to Otto F. Kernberg's 'Psychoanalysis, psychoanalytic psychotherapy
      and supportive psychotherapy: contemporary controversies'.

PMID- 10889975
TI  - 'Psychoanalysis, psychoanalytic psychotherapy and supportive psychotherapy:
      contemporary controversies' by Otto F. Kernberg

PMID- 10889976
TI  - Probing RNA structure and RNA-ligand complexes with chemical probes.

PMID- 10889977
TI  - Methylene blue-mediated cross-linking of proteins to double-stranded RNA.

PMID- 10889979
TI  - Applications of uranyl cleavage mapping of RNA structure.

PMID- 10889978
TI  - Structure and distance determination in RNA with copper phenanthroline probing.

PMID- 10889980
TI  - Identification of messenger RNAs that contain inosine.

PMID- 10889981
TI  - Site-specific 4-thiouridine incorporation into RNA molecules.

PMID- 10889982
TI  - Nucleoprotein photo-cross-linking using halopyrimidine-substituted RNAs.

PMID- 10889983
TI  - Structure determination by directed photo-cross-linking in large RNA molecules
      with site-specific psoralen.

PMID- 10889984
TI  - Photolabile derivatives of oligonucleotides as probes of ribosomal structure.

PMID- 10889985
TI  - Photoaffinity cross-linking and RNA structure analysis.

PMID- 10889986
TI  - Cleavage of RNA with synthetic ribonuclease mimics.

PMID- 10889987
TI  - Site-specific sulfhydryl groups for study of RNA conformation via disulfide cross
      linking.

PMID- 10889988
TI  - Directed hydroxyl radical probing using iron(II) tethered to RNA.

PMID- 10889989
TI  - In vitro selection of RNA aptamers.

PMID- 10889990
TI  - In vitro selection and characterization of RNAs with high affinity to
      antibiotics.

PMID- 10889991
TI  - Selection for RNA: peptide recognition through sulfur alkylation chemistry.

PMID- 10889992
TI  - In vitro selection of RNA substrates for ribonuclease P and its catalytic RNA.

PMID- 10889993
TI  - RNA-protein interactions in ribosomes: in vitro selection from randomly
      fragmented rRNA.

PMID- 10889994
TI  - Optimized synthesis of RNA-protein fusions for in vitro protein selection.

PMID- 10889995
TI  - Screening RNA-binding libraries by transcriptional antitermination in bacteria.

PMID- 10889996
TI  - Rapid genetic analysis of RNA-protein interactions by translational repression in
      Escherichia coli.

PMID- 10889997
TI  - RNA challenge phages as genetic tools for study of RNA-ligand interactions.

PMID- 10889998
TI  - Screening RNA-binding libraries using Tat-fusion system in mammalian cells.

PMID- 10889999
TI  - Frameshifting assay to characterize RNA-protein interactions in eukaryotic cells.

PMID- 10890000
TI  - Translational repression assay procedure: a method to study RNA-protein
      interactions in yeast.

PMID- 10890001
TI  - Analysis of low-abundance ribonucleoprotein particles from yeast by affinity
      chromatography and mass spectrometry microsequencing.

PMID- 10890002
TI  - Yeast three-hybrid system to detect and analyze RNA-protein interactions.

PMID- 10890003
TI  - Using peptides as models of RNA-protein interactions.

PMID- 10890004
TI  - Analysis of RNA-protein cross-link sites by matrix-assisted laser
      desorption/ionization mass spectrometry and N-terminal microsequencing.

PMID- 10890005
TI  - In vitro reconstitution of 30S ribosomal subunits using complete set of
      recombinant proteins.
AB  - This system allows convenient purification of large quantities of all of the
      small subunit ribosomal proteins by overexpression from cloned genes. This not
      only allows large-scale reconstitution of 30S subunits from individual proteins,
      but also facilitates protein purification greatly. These proteins can be
      reconstituted into functional 30S subunits using an ordered assembly protocol
      based on the in vitro 30S assembly map. Reconstitution of 30S subunits using this
      system enables mutant or modified proteins, such as Fe(II)-BABE-derivatized
      proteins, to be incorporated into subunits for studying ribosome structure and
      function.

PMID- 10890006
TI  - Directed hydroxyl radical probing of RNA from iron(II) tethered to proteins in
      ribonucleoprotein complexes.

PMID- 10890007
TI  - Use of dimethyl sulfate to probe RNA structure in vivo.

PMID- 10890008
TI  - Sensitive and high-resolution detection of RNA in situ.

PMID- 10890009
TI  - Assessment of ribozyme cleavage efficiency using reverse transcriptase real-time
      PCR.
AB  - Real-time PCR is a novel technology recently described to perform quantitative
      analysis of amplified products. Unlike classical quantitative PCR, this method is
      easy to standardize, does not required extensive manipulation, and is not reagent
      intensive, so that the risk of contamination is minimized. Therefore, we have
      chosen reverse transcriptase real-time PCR to quantitate CD95 (Fas) transcripts
      to test the cleavage efficiency of anti-Fas ribozymes in the mouse insulinoma
      cell line beta TC-3. Based on the melting-curve analysis of the amplified
      products, we determined the temperature at which to collect the fluorescent data
      used for quantification. After constructing a standard curve by plotting the log
      of the standards' copy number versus their fractional cycle number, the copy
      numbers of the unknown samples were automatically determined by interpolation of
      this curve. As we illustrate in this study, it is important, particularly while
      setting up the technique, to validate the melting-curve profile with standard gel
      electrophoresis analysis, achieved by matching melting temperature and size of
      the amplified product. The method is fast and reproducible: Excluding the
      isolation of RNA and synthesis of cDNA, the results can be obtained in less than
      1 hr. The coefficient of variance is 15% in the range of 10(4)-10(6) gene copies.
      Accordingly, reverse transcriptase (RT) real-time PCR is a technique suitable for
      screening a large number of ribozymes.

PMID- 10890010
TI  - A flow cytometric protocol for titering recombinant adenoviral vectors containing
      the green fluorescent protein.
AB  - As the use of adenoviral vectors in gene therapy protocols increases, there is a
      corresponding need for rapid, accurate, and reproducible titer methods. Multiple
      methods currently exist for determining titers of recombinant adenoviral vector,
      including optical absorbance, electron microscopy, fluorescent focus assay, and
      the "gold standard" plaque assay. This paper introduces a novel flow cytometric
      method for direct titer determination that relies on the expression of the green
      fluorescent protein (GFP), a tracking marker incorporated into several adenoviral
      vectors. This approach was compared to the plaque assay using 10(-4)- to 10(-6)
      fold dilutions of a cesium-chloride-purified, GFP expressing adenovirus (AdEasy +
      GFP + GAL). The two approaches yielded similar titers: 3.25 +/- 1.85 x 10(9)
      PFU/mL versus 3.46 +/- 0.76 x 10(9) green fluorescent units/(gfu/mL). The flow
      cytometric method is complete within 24 h in contrast to the 7 x 10 days required
      by the plaque assay. These results indicate that the GFU/mL is an alternative
      functional titer method for fluorescent-tagged adenoviral vectors.

PMID- 10890011
TI  - Comparison of competitive and positive control-based PCR quantitative procedures
      coupled with end point detection.
AB  - Two PCR methods using internal standards, coupled with our sandwich nonisotopic
      enzyme-linked oligosorbent assay (ELOSA) in microtiter plate format, were
      developed for quantitation of human immunodeficiency virus type 1 (HIV-1)
      provirus. We present an overview of both methodologies focusing on two major
      features, i.e., the conditions of equivalency of replication efficiency and the
      definition of criteria of acceptance validating a result. Quantitative
      competitive PCR (QC-PCR) was based on the coamplification of the HIV-1 nef gene
      with different amounts of a pNEFmut plasmid that contains the nef gene with
      different amounts of a pNEFmut plasmid that contains the nef region but with
      mutations in the capture probe recognition region. The NEF wild-type (NEF) and
      the NEF mimic (NEFmut) amplification products were differentiated in ELOSA.
      NEFmut OD to NEF OD ratios were plotted against the number of mimic copies, and
      the deduced linear curve permitted quantitation of HIV-1 copy number. Internally
      controlled PCR (IC-PCR) was based on coamplification of the HIV-1 nef gene with
      an internal endogenous standard, the ras gene, as a positive control of
      amplification. HIV-1 copy number was determined using external standard of known
      amounts of HIV-1 DNA. We address the advantages as well as the limitations of
      individuals protocols and discuss future improvements of quantitative
      amplification process.

PMID- 10890012
TI  - The use of somatic embryogenesis for plant propagation in cassava.
AB  - In cassava, somatic embryogenesis starts with the culture of leaf explants on
      solid Murashige and Skoog-based medium supplemented with auxins. Mature somatic
      embryos are formed within 6 wk. The cotyledons of the primary somatic embryos are
      used as explants for a new cycle of somatic embryogenesis. The cotyledons undergo
      secondary somatic embryogenesis on both liquid and solid Murashige and Skoog
      based medium supplemented with auxins. Depending on the auxin, new somatic
      embryos are formed after 14-30 d after which they can be used for a new cycle of
      somatic embryogenesis. In liquid medium, more than 20 secondary somatic embryos
      are formed per initial cultured embryo. In both primary and secondary somatic
      embryogenesis, the somatic embryos originate directly from the explants. Transfer
      of clumps of somatic embryos to a Gresshoff and Doy-based medium supplemented
      with auxins results in indirect somatic embryogenesis. The direct form of somatic
      embryogenesis has a high potential for use in plant propagation, whereas the
      indirect has a high potential for use in genetic modification of cassava. Mature
      somatic embryos germinate into plants after desiccation and culture on a
      Murashige and Skoog-based medium supplemented with benzylaminopurine (BA).
      Depending on the used BA concentration, plants can either be transferred either
      directly to the greenhouse or after using standard multiplication protocols.

PMID- 10890013
TI  - Fluorescent oligonucleotide ligation technology for identification of ras
      oncogene mutations.
AB  - A mutation detection strategy based on multiplex PCR followed by multiplex allele
      specific oligonucleotide probe ligation was developed to detect single nucleotide
      substitutions in ras oncogenes, a common genetic abnormality in many human
      cancers. Mutation-specific probes are synthesized for each possible single-base,
      nonsilent mutation in codons 12, 13, and 61 of H-, K-, and N-ras oncogenes.
      Mutations are identified by competitive oligonucleotide probe ligation to detect
      normal and/or mutant genotypes in one reaction. Three probes (one common and two
      allelic probes) are needed for analysis of each mutation. Probes hybridized to
      target ras oncogene DNA are joined by a thermostable ligase if there are no
      mismatches at their junctions; temperature cycling results in a linear increase
      in product. Common probes are labeled with fluorochromes, and allelic probes each
      have different lengths. Ligation products are analyzed by denaturing
      polyacrylamide gel electrophoresis on a fluorescent DNA sequencer. We have
      applied this technology to identify ras mutations in pancreatic cancers and lung
      cancers and in patients with myelodysplastic syndromes and leukemias.

PMID- 10890014
TI  - Analysis of genetically modified plant gene expression using GUS fluorimetry.
AB  - A fluorimetric assay method for the analysis of beta-glucuronidase (GUS) reporter
      gene expression in genetically modified plants is described. Optimization of this
      method for woody plants and a statistical approach suitable for comparisons of
      gene expression in different transformants or tissues of the same plant is
      described. Example data from elm (Ulmus procera) SR4 regenerant plants, shown to
      be genetically modified by PCR and DNA-DNA hybridizations, in which higher GUS
      expression levels are found in stems than in leaves demonstrates the utility of
      this approach.

PMID- 10890015
TI  - Analysis of glycoprotein heterogeneity by capillary electrophoresis and mass
      spectrometry.
AB  - Glycosylation is a complex posttranslational modification that can result in
      extensive heterogeneity for recombinant glycoproteins produced by eukaryotic
      systems. The carbohydrate moiety of a recombinant glycoprotein may affect the
      immunogenicity, half-life, bioactivity, and stability of a potential therapeutic
      product. Regulatory authorities such as the US Food and Drug Administration
      demand increasingly sophisticated carbohydrate analysis to ensure product
      characterization, batch-to-batch consistency, and stability. The advent of new
      technologies for analysis of biopolymers by capillary electrophoresis and mass
      spectrometry has revolutionized strategies for recombinant protein
      characterization. In particular, recent advances in matrix-assisted laser
      desorption/ionization and electrospray ionization mass spectrometry now permit
      relatively rapid and detailed assessment of glycoprotein and oligosaccharide
      structure. In this article, we describe some applications of capillary
      electrophoresis and mass spectrometry to monitor the glycosylation associated
      with a model recombinant glycoprotein, human interferon-gamma.

PMID- 10890016
TI  - Detection of autoantibodies to cytokines.
AB  - Autoantibodies to various cytokines have been reported in normal individuals and
      in patients with various infectious and immunoinflammatory disorders, and similar
      antibodies (Ab) may be induced in patients receiving human recombinant cytokines.
      The clinical relevance of these Ab is often difficult to evaluate. Not only are
      in vitro neutralizing cytokine Ab not necessarily neutralizing in vivo, but
      assays for binding and neutralizing Ab to cytokines are often difficult to
      interpret. For example, denaturation of immobilized cytokines in immunoblotting
      techniques and immunometric assays may leave Ab to the native forms of the
      mediators unrecognized. On the other hand, Ab may bind nonspecifically and/or
      with biologically irrelevant low affinities, leading to erroneous
      interpretations. This article describes in detail the use of radioimmunoassays
      that we have optimized and used successfully for the detection of high-affinity
      (auto) Ab to IL-1 alpha, IL-6, GM-CSF, and IFN alpha.

PMID- 10890017
TI  - [Psychotropic agents may induce de novo nonconvulsive status epilepticus].
AB  - Nonconvulsive status epilepticus (NCSE) shows a prolonged state of confusion and
      psychosis accompanied by many different kinds of continuous epileptic discharges.
      NCSE may occur not only in epileptic patients but also in adults with no previous
      history of epilepsy. Some de novo NCSE may be caused by the administration of
      psychotropic agents such as antidepressants and neuroleptics and withdrawal from
      benzodiazepines. However, little attention has been paid to such de novo NCSE in
      Japan. Previous reports with respect to psychotropic drug-related NCSE were
      reviewed.

PMID- 10890018
TI  - [Antinociceptive effects of the enantiomorphs and its main metabolite in
      streptozotocin-induced diabetic mice].
AB  - The antinociceptive effects of the enantiomorphs of mexiletine (2-(2, 6
      dimethylphenoxy)-1-methylethylamine monohydrochloride) and its main metabolite
      ((+/-)2-(2-hydroxymethyl-6-methylphenoxy)-1-methylethylamine oxalate: KOE2259)
      were studied in streptozotocin-induced diabetic mice using the tail-pinch and
      tail-flick test. Both (+)mexiletine and (-)mexiletine, at doses of 10 and 30 mg
      given i.p., produced dose-dependent inhibition of the tail-pinch response in
      diabetic, but not non-diabetic mice. On the other hand, KOE2259 had no
      significant effect on the tail-pinch response in both non-diabetic and diabetic
      mice. (+/-) Mexiletine given po also produced marked inhibition of the tail-pinch
      and tail-flick responses in both non-diabetic and diabetic mice. However,
      lidocaine, given either i.p. or po, had no significant effect on the tail-pinch
      response in both non-diabetic and diabetic mice. Intraperitoneal administration
      of mexiletine (30 mg/kg) significantly increased the serum beta-endorphin level
      in diabetic mice, but not in non-diabetic mice. These results indicate that both
      enantiomorphs of mexiletine produced an antinociceptive effect in diabetic mice.
      Furthermore, it is possible that the activation of the endogenous beta
      endorphinergic system may be, at least in part, involved in the antinociceptive
      effect of mexiletine.

PMID- 10890019
TI  - Serial position effect and selective amnesia induced by scopolamine in mice.
AB  - Mice were trained to run through a maze with six gates, each consisting of three
      doors--two locked and one unlocked. They learned to choose a correct (unlocked)
      door at the gates close to the beginning and end better than in the middle,
      showing the primacy and recency effects of serial learning. A low dose of
      scopolamine unexpectedly enhanced the primacy effect, while a high dose impaired
      learning in general. The enhancement of the primacy effect can be explained in
      terms of reduction of retroactive interference.

PMID- 10890020
TI  - [Neural stem cells: the basic biology and prospects for brain repair].
AB  - Neural stem cells (NSCs) are multipotential progenitor cells that have self
      renewal activities. A single NSC is capable of generating various kinds of cells
      within the CNS, including neurons, astrocytes, and oligodendrocytes. Because of
      these characteristics, there is an increasing interest in NSCs and neural
      progenitor cells from the aspects of both basic developmental biology and
      therapeutic applications for damaged brain. By understanding the nature of NSCs
      present in the CNS, extracellular factors and signal transduction cascades
      involved in the differentiation and maintenance of NSCs, population dynamics and
      localization of NSCs in embryonic and adult brains, prospective identification
      and isolation of NSCs, and induction of NSCs into particular neuronal phenotypes,
      it would be possible to develop a feasible strategy to manipulate cells in situ
      to treat damaged brain.

PMID- 10890021
TI  - [Molecular genetics of satori, a Drosophila mutant with altered sexual
      orientation].
AB  - satori (sat) is a Drosophila mutant in which male sexual orientation changes from
      heterosexual to homosexual. Another phenotype of the satori mutant is the absence
      of the male-specific muscle of Lawrence (MOL). The formation of MOL is repressed
      in females by the action of a female-determinant protein. Transformer (Tra),
      while a Tra-target doublesex (dsx) has no role in the MOL formation. Molecular
      cloning of the fruitless (fru) gene responsible for the sat mutation revealed
      that it encodes a putative transcription factor with a BTB domain and Zn finger
      motifs, and that the second exon of this gene contains three repeats of the Tra
      binding consensus sequence. These observations suggest that fru is a novel target
      of Tra in the sex determination cascade of Drosophila. MOL formation is known to
      occur when the sex of the innervating motoneuron is male regardless of the sex of
      the MOL itself. Taking into account the fact that Fru is preferentially expressed
      in the nervous system, Fru is likely involved in neuronal sex determination. We
      hypothesize that the sat mutation feminizes a class of neurons which otherwise
      promote heterosexual courtship and the formation of the MOL in males.

PMID- 10890022
TI  - [Endogenous D-serine in mammalian brains].
AB  - It is well established that, like glycine and D-alanine, D-serine potentiates
      glutamate neurotransmission via the N-methyl-D-aspartate (NMDA) receptor by
      selective stimulation of its strychnine-insensitive glycine site and acts as a co
      agonist of the glutamate receptor. D-Serine has been found to modify behavioral
      changes associated with higher brain functions such as memory, convulsion,
      anxiety, psychotomimetic-induced abnormal behavior and cerebellar ataxia.
      Interestingly, a substantial amount of free D-serine has been demonstrated in
      mammalian brains, although it has long been presumed that D-amino acids are
      uncommon in mammals. Free D-serine is predominantly concentrated in the brain
      with a persistent high content throughout life. The patterns of the regional
      variations and the postnatal changes in brain D-serine are closely correlated
      with those of the R2B subunit of the N-methyl-D-aspartate (NMDA) type excitatory
      amino acid receptor. Moreover, D-serine is released to the extracellular space
      and taken up into the brain homogenates, C6 glioma cells and primary culture of
      astrocytes of the rat cerebral cortex. Recently, the conversion of L-serine to
      its D-form by serine racemase has been suggested by in vivo and in vitro
      experiments. These data are consistent with the view that D-serine might be an
      intrinsic positive modulator of the brain NMDA receptor containing the R2B
      subunit and play a pivotal role in controlling behavioral expression in mammals.

PMID- 10890023
TI  - Are dietary fiber-induced alterations in colonic epithelial cell proliferation
      predictive of fiber's effect on colon cancer?
AB  - Alterations in cell proliferation of the colon have been observed as a result of
      changes in amount and type of dietary fiber and in relation to risk of developing
      colon cancer. Although some human observational and intervention studies
      contribute to the database, most information results from experiments on rodents.
      Because of numerous contradictory reports linking dietary fiber, cell
      proliferation, and colon cancer, we undertook a critical review of existing
      methods in an attempt to explain the inconsistencies. Although there may be some
      individual types of dietary fiber that protect against chemically induced colon
      cancer, dietary fiber as a single entity does not appear to afford any consistent
      protection. Because of significant differences in experimental protocols among
      laboratories, it is not yet possible to state with certainty that increases in
      cell proliferation, induced by fiber consumption, are predictive of increased
      tumorigenesis. Much of what has been observed and interpreted as elevation of
      risk may simply be normal homeostatic changes in cell proliferation. Even though
      fermentation to short-chain fatty acids is a mechanistically attractive
      hypothesis to explain why fiber modulates cytokinetics, data do not consistently
      support short-chain fatty acids as biological intermediates in risk of colon
      cancer. The state of the art in this field has not yet progressed to the point
      where a clear effect of dietary fiber on cytokinetics and colon carcinogenesis
      can be assessed with any degree of certainty. Additional markers of apoptosis,
      differentiation, and cell-cell communication may be required for a more accurate
      analysis of the relation among fiber, cytokinetics, and colon cancer.

PMID- 10890024
TI  - Role of thiamin (vitamin B-1) and transketolase in tumor cell proliferation.
AB  - Metabolic control analysis predicts that stimulators of transketolase enzyme
      synthesis such as thiamin (vitamin B-1) support a high rate of nucleic acid
      ribose synthesis necessary for tumor cell survival, chemotherapy resistance, and
      proliferation. Metabolic control analysis also predicts that transketolase
      inhibitor drugs will have the opposite effect on tumor cells. This may have
      important implications in the nutrition and future treatment of patients with
      cancer.

PMID- 10890025
TI  - Fat intake and risk of squamous cell carcinoma of the skin.
AB  - The varied effects of different classes of dietary fatty acids on carcinogenesis
      suggest that fatty acid composition is an important determining factor in tumor
      development. In the present study, we investigated the association between
      dietary n-3 and n-6 fatty acid intake and risk of squamous cell carcinoma of the
      skin (SCC). Data were taken from a population-based case-control study of skin
      SCC in Southeastern Arizona. Our data show a consistent tendency for a lower risk
      of SCC with higher intakes of n-3 fatty acids [p (for trend) = 0.055]. The
      adjusted odds ratios for increasing levels of n-3 fatty acids were 0.85 [95%
      confidence interval (CI) = 0.56-1.27] and 0.71 (95% CI = 0.49-1.00) compared with
      the lower level as the referent. For the ratio of n-3 to n-6 fatty acids, the
      odds ratios in successively higher levels were 0.88 (95% CI = 0.59-1.32) and 0.74
      (95% CI = 0.51-1.05), suggesting a tendency toward decreased risk of SCC with
      increased intake of diets with high ratio of n-3 to n-6 fatty acid. More studies
      are clearly needed to elucidate the function of dietary fatty acids so that
      recommendations can be made to alter the human diet for cancer prevention,
      particularly in light of the increasing incidence of SCC of the skin.

PMID- 10890026
TI  - Correlates of serum lycopene in older women.
AB  - Experimental and epidemiological evidence suggests that lycopene, a predominant
      carotenoid found in human serum, may reduce the risk of certain cancers. We
      examined the association of dietary, physiological, and other factors with serum
      lycopene concentrations in a subsample of 946 postmenopausal women participating
      in the Women's Health Initiative. Pearson partial correlation coefficients and
      linear regression coefficients were calculated after adjustment for age,
      ethnicity, and serum low-density-lipoprotein (LDL) cholesterol. Serum lycopene
      was correlated with serum LDL cholesterol (r = 0.23) and dietary lycopene (r =
      0.17, both p < 0.001). Individual food items found to be correlated with serum
      lycopene after adjustment included fresh tomatoes or tomato juice (r = 0.11),
      cooked tomatoes, tomato sauce, or salsa (r = 0.17), and spaghetti with meat sauce
      (r = 0.19, all p < 0.01). Age and body mass index were negatively associated with
      serum lycopene levels (both p < 0.001). Serum lycopene levels were highest in the
      summer and highest for those living in the northeastern United States. If we
      postulate that high serum lycopene levels reduce cancer risk, it becomes apparent
      that we have limited ability to detect this association from studies of lycopene
      intake. An understanding of factors associated with serum lycopene levels can be
      useful for the interpretation of studies of dietary lycopene and disease risk.

PMID- 10890027
TI  - Eating frequency and risk of colorectal cancer.
AB  - Case-control studies have found elevated risk of colorectal cancer with higher
      eating frequency. The present analyses, the first to examine this association
      using prospectively collected information, utilized nationally representative
      data from the Epidemiologic Follow-Up Study of the First National Health and
      Nutrition Examination Survey (NHEFS). The study population included 9,978
      subjects followed from 1982-84 to 1992. Colorectal cancer cases (n = 141) were
      identified by self-report, hospital records, and death certificates. Interviews
      conducted in 1982-84 provided information on meal and snack frequencies and
      covariates of interest. Relative risk (RR) of colorectal cancer and 95%
      confidence intervals (CI) were estimated using Cox proportional hazards models
      adjusted for age, gender, and race and energy, alcohol, total fat, and fiber
      intake. Compared with those eating < 3 times/day, those eating 3-4 times/day had
      an RR of 0.66 (95% CI = 0.42-1.03) and those eating > 4 times/day had an RR of
      0.74 (95% CI = 0.41-1.32). The association was due to decreased risk with more
      meals rather than more snacks per day. Given limitations of previous studies as
      well as the possibility of a protective effect of higher eating frequency through
      improved glycemic control, the present findings suggest that the influence of
      eating frequency on colorectal cancer risk is more complex than has been
      previously supposed and merits additional study.

PMID- 10890028
TI  - Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic
      cancer.
AB  - Eicosapentaenoic acid (EPA) has been shown to modulate aspects of the
      inflammatory response that may contribute to weight loss in cancer. This study
      aimed to evaluate the acceptability and effects of oral supplementation with high
      purity EPA in weight-losing patients with advanced pancreatic cancer. Twenty-six
      patients were entered into the study. EPA (95% pure) was administered as free
      acid starting at 1 g/day; the dose was increased to 6 g/day over four weeks, and
      then a maintenance dose of 6 g/day was administered. Patients were assessed
      before EPA and at 4, 8, and 12 weeks while receiving EPA, for weight, body
      composition, hematologic and clinical chemistry variables, acute-phase protein
      response, and performance status. Overall survival was noted. Supplementation was
      well tolerated, with only five patients experiencing side effects possibly
      attributable to the EPA. Before starting EPA, all patients had been losing weight
      at a median rate of 2 kg/mo. In general, after EPA supplementation, weight was
      stable. After four weeks of EPA supplementation, patients had a median weight
      gain of 0.5 kg (p = 0.0009 vs. rate of weight loss at baseline), and this
      stabilization of weight persisted over the 12-week study period. Total body water
      as a percentage of body weight remained stable, as did the proportion of patients
      with an acute-phase protein response, patients' nutritional intake, and
      performance status. Overall median survival from diagnosis in this study was 203
      days. This study suggests that EPA is well tolerated, may stabilize weight in
      cachectic pancreatic cancer patients, and should be tested as an anticachectic
      agent in controlled trials.

PMID- 10890029
TI  - beta-Carotene stability and uptake by prostate cancer cells are dependent on
      delivery vehicle.
AB  - Cell culture systems provide an opportunity to evaluate the effects of
      carotenoids on molecular and cellular processes involved in proliferation and
      differentiation of prostate cancer cells. The stability and cellular uptake of
      beta-carotene (BC) by prostate cancer cells were investigated in vitro by use of
      various delivery methods and three human prostate adenocarcinoma cell lines: PC
      3, DU 145, and LNCaP. Recovery of BC from the media (prepared from water
      dispersible BC beadlets) significantly (p < 0.05) decreased after 12 hours in
      culture and continued to significantly decrease (p < 0.05) after 24, 48, 72, and
      96 hours, an observation primarily attributed to BC degradation rather than
      isomerization, metabolism, or cellular uptake. The uptake of BC by prostate
      cancer cells was compared when delivered by tetrahydrofuran, BC-enriched bovine
      serum, water-dispersible BC beadlets, and artificial liposomes. Recovery of BC
      after three days in culture from enriched bovine serum medium was significantly
      (p < 0.05) greater than recovery from medium prepared by beadlets,
      tetrahydrofuran, or artificial liposomes. We conclude that BC is relatively
      unstable in vitro and that degradation products may contribute to biological
      responses. Furthermore, our studies indicate that enriched bovine serum provides
      a stable and physiological approach to carotenoid treatment of cells in culture.

PMID- 10890030
TI  - In vitro absorption and metabolism of a citrus chemopreventive agent, auraptene,
      and its modifying effects on xenobiotic enzyme activities in mouse livers.
AB  - We previously reported that auraptene (7-geranyloxycoumarin, AUR), widely
      occurring in citrus fruit, is a structurally novel type of effective cancer
      preventive agent, as manifested in several rodent models. However, its bio
      availability and metabolism in biological systems have yet to be investigated. In
      the present study, we examined the chemical stability of AUR at pH 1.57 and 37
      degrees C (as a stomach digestion model) and observed its stoichiometric
      conversion to umbelliferone [7-hydroxycoumarin, UMB; half-life (t1/2) = 15 h; 7
      ethoxycoumarin (ETC) was stable for 24 h]. Differentiated Caco-2 cells, a human
      colorectal adenocarcinoma cell line, were used as a small intestine model. ETC
      permeated the basolateral (portal vein) side of Caco-2 cells in a time-dependent
      manner; AUR slightly permeated the cells, but with an intracellular accumulation.
      Epoxyauraptene and UMB were detected when AUR was treated with the rat liver S-9
      mixture. ETC was also converted to UMB, but its t1/2 of two hours was much
      shorter than that of AUR (> 24 h). This suggests that AUR, bearing a geranyloxyl
      side chain, is a relatively metabolism-resistant substrate for cytochrome P-450
      enzymes and, thus, is stable in the liver compared with ETC. Oral administration
      of AUR by gavage at 50-200 mg/kg body wt dose dependently induced glutathione S
      transferase (GST) activity in mouse livers without affecting cytochrome P-450
      activity. Using 10 coumarin-related compounds, we found that only those coumarins
      having a 7-alkyloxyl group induced GST, but not cytochrome P-450, activity. The
      present study presumes that AUR accumulates in the epithelial cells of the small
      intestine and then gradually permeates into the portal vein. Stable
      localizability of AUR in the colon and liver may be associated with the induction
      of GST activity, which is important as the action mechanism for suppression of
      rodent chemical carcinogenesis.

PMID- 10890031
TI  - Use of arginine to reduce the severity of retinoid-induced hypertriglyceridemia.
AB  - Previous research with an animal model of retinoid-induced hypertriglyceridemia,
      rats fed a 13-cis retinoic acid-containing diet in which casein was the dietary
      protein, has demonstrated that replacement of dietary casein with soy protein
      isolate can reduce the severity of this condition. A depressant action of soy
      protein vs. that of casein on serum triglyceride concentration has also been
      demonstrated in rats fed purified diets without supplemental retinoid. Because
      this action of soy protein appears to be due to its having a higher arginine-to
      lysine ratio than casein, a study was done to determine how feeding a casein
      containing diet supplemented with sufficient arginine, to give a dietary arginine
      to-lysine ratio equivalent to that of soy protein, would affect the development
      of retinoid-induced hypertriglyceridemia. Groups of five-week-old male Fischer
      344 rats (n = 7/group) were fed a control diet containing casein or one of three
      13-cis retinoic acid-containing diets in which dietary nitrogen was provided as
      casein, casein + arginine, or soy protein. Incorporation of dietary 13-cis
      retinoic acid resulted in hypertriglyceridemia, with serum triglyceride
      concentrations of 2.00 and 7.23 mmol/l, or 177 and 640 mg/dl, for groups fed the
      control and casein + 13-cis retinoic acid diets, respectively. For animals fed
      the 13-cis retinoic acid-containing diets, serum triglyceride levels for the
      casein + arginine and soy protein diet groups (4.75 and 2.92 mmol/l, or 421 and
      258 mg/dl, respectively) were significantly lower than for the casein group (p <
      0.05); however, the value was significantly lower for the group fed the soy
      protein diet than for the group fed the casein + arginine diet. Serum and dietary
      arginine-to-lysine ratios were highly correlated (r = 0.93, p < 0.0001). Thus,
      supplementing dietary casein with arginine reduced the severity of retinoid
      induced hypertriglyceridemia, but not as effectively as replacing casein with soy
      protein.

PMID- 10890032
TI  - Hydroxymatairesinol, a novel enterolactone precursor with antitumor properties
      from coniferous tree (Picea abies).
AB  - The potential for the extraction of the plant lignan hydroxymatairesinol (HMR) in
      large scale from Norway spruce (Picea abies) has given us the opportunity to
      study the metabolism and biological actions of HMR in animals. HMR, the most
      abundant single component of spruce lignans, was metabolized to enterolactone
      (ENL) as the major metabolite in rats after oral administration. The amounts of
      urinary ENL increased with the dose of HMR (from 3 to 50 mg/kg), and only minor
      amounts of unmetabolized HMR isomers and other lignans were found in urine. HMR
      (15 mg/kg body wt po) given for 51 days decreased the number of growing tumors
      and increased the proportion of regressing and stabilized tumors in the rat
      dimethylbenz[a]anthracene-induced mammary tumor model. HMR (50 mg/kg body wt) did
      not exert estrogenic or antiestrogenic activity in the uterine growth test in
      immature rats. HMR also showed no antiandrogenic responses in the growth of
      accessory sex glands in adult male rats. Neither ENL nor enterodiol showed
      estrogenic or antiestrogenic activity via a classical alpha- or beta-type
      estrogen receptor-mediated pathway in vitro at < 1.0 microM. HMR was an effective
      antioxidant in vitro.

PMID- 10890033
TI  - Dietary butyrate inhibits NMU-induced mammary cancer in rats.
AB  - Butyrate has been proposed as an antineoplastic agent, leading to the inhibition
      of tumorigenesis. The purpose of this study was to examine butyrate, supplied as
      tributyrin (Tbn) or as a natural component of anhydrous milk fat (AMF), on the
      development of nitrosomethylurea-induced mammary tumors in female Sprague-Dawley
      rats. Diets were 1) semipurified rodent diet (AIN-93) with high fat [20%
      sunflower seed oil (SSO), control], 2) SSO diet with Tbn added at 1%, 3) SSO diet
      with Tbn added at 3%, and 4) 19% AMF with 1% SSO diet, which contained butyrate
      equivalent to the 1% Tbn diet. These diets were fed ad libitum from weaning at 21
      days of age, and at 24 days of age each rat was injected with nitrosomethylurea
      (50 mg/kg body wt i.p.). At any one period, there was a relative risk increase of
      88% (p < 0.05) that rats in the SSO diet group would develop a mammary tumor
      compared with those in the AMF diet group. The addition of 1% and 3% Tbn to SSO
      diets reduced the tumor incidence by 20% and 52%, respectively, in comparison to
      SSO alone (p < 0.05). There was a linear inverse relationship between Tbn
      concentration and rats developing a tumor. From 89 days to the end of the
      experiment, rats fed the diet containing 3% Tbn showed a significantly lower
      multiplicity of palpable tumors (50% less at Day 118, p < 0.05) than SSO-fed
      rats. These results indicate that although the AMF diet was effective,
      particularly early in reducing mammary tumorigenesis, the 3% Tbn diet produced a
      sustained reduction of tumor multiplicity relative to the control (SSO) group. An
      inhibitory influence of butyrate on mammary tumorigenesis against a background of
      high polyunsaturated fat diet has been demonstrated in this animal model of
      breast cancer.

PMID- 10890034
TI  - Inhibition of azoxymethane-induced colon cancer by orange juice.
AB  - Previous research has shown that hesperidin, a flavanone glycoside in orange
      juice, inhibits colon carcinogenesis and that feeding double-strength orange
      juice delays the onset of chemically induced mammary cancer in rats. This study
      determined whether feeding single-strength, pasteurized orange juice would
      inhibit azoxymethane (AOM)-induced colon cancer in male Fischer 344 rats. Colon
      cancer was initiated by injecting AOM (15 mg/kg body wt) at 22 and 29 days of
      age. One week after the second AOM injection, orange juice replaced drinking
      water for the experimental group (n = 30). The rats were killed 28 weeks later,
      and tumors were removed for histological analysis. Feeding orange juice reduced
      tumor incidence by 22% (p < 0.05). Tumor reduction was associated with a
      decreased labeling index and proliferation zone in the colonic mucosa.
      Hesperidin, other flavonoids, limonin 17-beta-D-glucopyranoside, and other
      limonoid glucosides are potential chemopreventive agents in orange juice that
      could account for the decreased colon tumorigenesis associated with feeding
      orange juice.

PMID- 10890035
TI  - Comparative effects of three resistant starch preparations on transit time and
      short-chain fatty acid production in rats.
AB  - A high-fiber diet may protect against colon cancer because of the butyrate
      generated in the colon by bacterial fermentation of nonstarch polysaccharides.
      Butryrate can reverse neoplastic changes, at least in vitro, and resistant starch
      (RS) represents a source of butyrate in vivo. We examined the effects of
      replacing normal maize starch in the diet of rats with three preparations of RS
      on the amounts of starch, butyrate, and other short-chain fatty acids in the
      cecum. We examined the effects on fecal bulking and transit time, which have been
      suggested to protect against colon cancer. The RS preparations that we tested
      were potato starch, high-amylose maize starch, and an alpha-amylase-treated high
      amylose maize starch. All had major effects on fecal weight and on the weight of
      the cecum but only slightly shortened transit times. All increased the amount of
      starch reaching the cecum and increased short-chain fatty acid production in the
      cecum; potato starch had the greatest effect and high-amylose maize starch the
      least. Potato starch, unlike high-amylose maize starch, enhanced the proportion
      of butyrate. Thus there were marked differences among sources of RS, even though
      these were all classified as RS2. The significance for colon cancer is discussed.

PMID- 10890036
TI  - Peanuts as a source of beta-sitosterol, a sterol with anticancer properties.
AB  - Work from our laboratory, as well as others, suggests a protective role of
      phytosterols (PS), especially beta-sitosterol, from colon, prostate, and breast
      cancer. Asians and vegetarians consume higher amounts of PS than Western
      societies. The latter societies have a higher incidence of these cancers than
      Asians and vegetarians. The aim of this study was to evaluate peanuts and its
      products as sources of PS in the American diet. Roasted peanuts contain 61-114 mg
      PS/100 g depending on the peanut variety, 78-83% of which is in the form of beta
      sitosterol. Unrefined peanut oil contains 207 mg PS/100 g, which is similar to
      that of the US Department of Agriculture Nutrient Database. This value is higher
      than that of unrefined olive oil. Refining these oils results in reduction in PS
      concentration in the oil. This loss is greater in the case of olive oil than
      peanut oil. Further refining, such as deodorization, results in significant loss
      in PS, but hydrogenation after refining has a minimal effect on PS loss. Peanut
      butter, which represents 50% of the peanuts consumed in the United States,
      contains 144-157 mg PS/100 g. Peanut flour, which results from partial removal of
      oil from peanuts, contains 55-60 mg PS/100 g. The data suggest that peanuts and
      its products, such as peanut oil, peanut butter, and peanut flour, are good
      sources of PS.

PMID- 10890037
TI  - [The anatomy and function of the pelvic floor].
AB  - PELVIC FLOOR: Anatomy of the pelvic floor seemed to be clearly. In opposite the
      physiology of the Levator ani and the endopelvic fascia is not yet fully
      understood. Especially the anatomic form of the levator plate does not conform
      with physiologic concepts. PELVIC STRUCTURES: Pelvic structures can be divided in
      three groups: the hollow organs, the endopelvic fascia and the muscles. The M.
      levator ani is the muscle of the pelvic diaphragm. Its parts were given different
      names (Fig. 1, 4) depending on their function or localization. In anatomic
      studies the pelvic floor is described as basin-shaped. In contrast to the
      anatomic results based upon the evaluation of cadavers, dynamic MRI gave
      different concepts: at rest the levator ani probably has the shape of a dome and
      differ when contract. The urogenital diaphragm is mostly a fascia and contains
      only fair muscular components. Therefore, many authors do not accept the term
      "diaphragm" and the physiologic function is still a matter of discussion. The
      endopelvic fascia has to fix the organs in the pelvis and forms "streets" for
      vascular and nervous supply. CONCLUSION: Describing anatomic structures in the
      common planes (transversal, sagittal, frontal) will help to understand CT- and
      MRI-imaging.

PMID- 10890038
TI  - [Morphological and functional pelvic floor disorders from the gynecological
      viewpoint].
AB  - PURPOSE: The following article is designed to describe the diagnostics and
      therapy of morphological and functional defects in the female pelvic floor from a
      gynaecological point of view. Assessment of the relevance of imaging techniques
      is of particular importance. MATERIAL AND METHODS: The main diagnoses are: in the
      anterior compartment of the pelvic floor, urethro- cystocele; in the middle
      compartment, uterine descent/prolapse or enterocele; and in the posterior
      compartment, rectocele. They are clinically examined by means of a standardised
      gynaecological examination and classified according to recommendations from the
      International Continence Society (ICS) in order to obtain internationally
      comparable results. Comparison with the usual imaging procedures (introitus- and
      perineal sonography, colpocystorectography/defaecography and functional MRI of
      the pelvic floor) are described and critically discussed. The most important
      functions affected are storage and evacuation of the bladder and rectum. They are
      clinically examined by means of stress test and padweigh test and technically
      examined using urodynamics, sphincter-rectum manometry and EMG. Imaging
      procedures play a very important role here also. RESULTS: Comparison of clinical
      and imaging procedures shows that the two methods are at present limited in
      comparability, mainly because different points of reference are used to quantify
      results. The line of the hymen is a good point of reference in grading descent
      and prolapse. During the gynaecological examination, the three compartments can
      readily be assessed separately by use of split gynaecological specula. This is
      presently practically impossible using imaging procedures. The pubococcygeal line
      is generally used to describe findings. DISCUSSION: Scientific progress can only
      be expected if and when these problems are studied as a whole. Imaging procedures
      have securely established themselves in the diagnostic repertoire, but do not as
      yet influence therapy decisions. The indication and choice of operation depend on
      the severity of the patient's symptoms the clinical findings and the results of
      urodynamic investigations. Dynamic CTG is presently the most reliable method of
      showing all three compartments at rest and during function. It has largely
      replaced colpocystorectography. Sonography is found to be varied in ist results
      at the moment.

PMID- 10890039
TI  - [Coloproctological diseases of the pelvic floor].
AB  - PURPOSE: The aim of this review is to describe the most frequent and important
      coloproctologic pelvic floor disorders. Relevant diagnostic procedures of the
      pelvic floor will be presented. MATERIAL AND METHODS: A host of diagnoses and
      symptoms such as the descending perineum syndrome, rectocele, cystocele,
      enterocele, uterine and vaginal descensus, anal and rectal prolapse, outlet
      obstruction, anismus, inertia recti and intussusception are included under the
      heading "pelvic floor disorders". Although symptoms are often varied, problems
      concerning urinary and/or faecal continence commonly lead to primary consultation
      of a physician. RESULTS: Quite often, apparently divergent symptoms such as
      constipation and incontinence are simultaneously mentioned. A clear gender
      disposition is observed with female patients inflicted nine-fold in comparison to
      male patients. The primary consultant may belong to a variety of specialities
      such as urology, proctology, gynaecology or dermatology, depending upon the
      predominant symptom. A feeling of trust is essential for the treatment of a
      disorder involving highly intimate regions of the body. DISCUSSION: An exact
      medical history and standardized proctologic evaluation consisting of inspection,
      palpation, rectoscopy and proctoscopy may be augmented by investigations such as
      anorectal manometry or endosonography. Conventional defecography has been
      replaced more and more by dynamic MRI of the pelvic floor in specialized
      institutions, enabling additional gynaecologic and urologic investigations
      avoiding ionizing radiation.

PMID- 10890040
TI  - [Functional MRI of the pelvic floor: its normal anatomy and pathological
      findings].
AB  - PURPOSE: Functional MRI of the pelvic floor allows mapping and definition of
      different forms of pelvic floor dysfunction. METHODS: We performed functional MRT
      of the pelvic floor in 39 healthy nulliparas and 324 patients. The diagnosis of a
      pathological organ descent was made if certain landmarks of the pelvic floor
      compartments descended below the pubococcygeal reference-line (PC-line). RESULTS:
      If there was no organ descent below the PC-line on straining and if the pelvic
      floor muscles hardly changed position, a normal finding was diagnosed. 70% of
      organ prolapses came in the combined form. The generally gradual development of
      an organ descent led to a change of the main finding in 21.6%. The masking of a
      cystocele (48.6%) or of an enterocele (34.3%) by a rectocele was most frequent in
      these cases. DISCUSSION: The use of functional MRI of the pelvic floor appears to
      be especially useful in young patients, in cases of divergent clinical and
      sonographic or radiological findings and if the presence of a predominant hernial
      sac with or without enterocele/rectocele is supposed.

PMID- 10890041
TI  - [Functional MRI of the pelvic floor. The methods and reference values].
AB  - PURPOSE: Functional cine MRI of the pelvic floor is a yet another modality in
      addition to various radiological fluoroscopic techniques. This article describes
      our own method in view of the recent literature and provides morphometric
      reference values. MATERIAL AND METHOD: We examined 20 nulliparous women (range of
      age: 25-51 years) with normal findings in the gynecological and urodynamic
      examination. Functional cine MRI was performed on a 1.5 Tesla equipment after
      opacification of the vagina and rectum. We used a T2-weighted gradient-echo
      sequence (Ture-FISP) to determine the position of the reference organs at rest
      and during straining/defecation. Two different reference lines were used. In
      addition 29 morphometric and functional parameters were measured, all of them
      being observer independent. RESULTS: Functional cine MRI was able to show the
      extent and interaction of the pelvic floor organs in all cases with the reference
      organs always remaining above the pubococcygeal reference line. The depth of the
      rectocele was 2 cm. With the exception of the diameter of urogenital hiatus the
      different parts of the levator ani muscle could not be determined. DISCUSSION:
      Functional cine MRI using an appropriate organ opacification and slice
      positioning is an objective, unifying diagnostic approach of the pelvic floor.
      The reference data given can be of help to distinguish normal from abnormal
      findings.

PMID- 10890042
TI  - [Endoanal magnetic resonance tomography in fecal incontinence].
AB  - PURPOSE: Within the recent years several studies have been performed to determine
      the value of endoanal magnetic resonance imaging (MRI) in faecal incontinence.
      METHODS: MRI is performed using a 0.5-1.5 T unit. A surface coil with a maximum
      diameter of 19 mm is placed in the anal canal. T2* 3D gradient-echo-sequences and
      T2-weighted turbo-spin-echo sequences in coronal, axial und sagittal orientation
      are acquired. RESULTS: Compared to endoanal ultrasound (EUS), which is the gold
      standard for diagnosis in faecal incontinence, endoanal MRI is better in
      visualization of the external sphincter. The accurate delineation of the external
      sphincter has led to the possibility to evaluate sphincter atrophy. Preliminary
      results have shown, that endoanal MRI has an accuracy of 90-95% in the
      demonstration of lesions in the external sphincter. In detection of lesions of
      the internal sphincter EUS is still superior to endoanal MRI. CONCLUSION: EUS and
      endoanal MRI are currently the optimal imaging techniques for faecal
      incontinence, with the advantage of detecting external sphincter atrophy with
      endoanal MRI.

PMID- 10890043
TI  - [The nutritive vascular canals. The magnetic resonance differential diagnosis of
      carpal cystic lesions?].
AB  - PURPOSE: To find and describe potential MRI criteria of nutrient vessel canals of
      carpal bones. METHODS AND MATERIAL: 16 wrists of 13 patients with pain and
      radiographic depiction of cystic changes within the lunate were examined. The MRI
      protocol included coronal and sagittal T1- and T2-weighted SE sequences (4 mm
      slices, 120 FOV, 256 x 256 matrix) as well as coronal STIR images. Final
      diagnosis was confirmed by surgery (n = 5) and follow up. 10 cadaveric ossa
      lunata were studied to describe size, number, location and shape of nutrient
      vessel canals. RESULTS: Ganglion cysts (n = 6) showed characteristic signs. In
      ulnar impaction syndrome (n = 1) small cystic lesions in the lunate were
      surrounded by a sclerotic rim and located near the proximal ulnar surface. In
      Kienbock's disease (n = 3) cystic components were irregular and surrounded by
      bone marrow edema. Nutrient vessel canals (n = 7) imaged as 1 to 3 small cystic
      lesions within the palmar or dorsal subchondral region. CONCLUSION: MRI can aid
      in differential diagnosis of cystic carpal lesions. Nutrient vessel canals may
      not be mistaken for pathologic cystic lesions. Carpal ganglion cysts show
      distinct diagnostic pattern.

PMID- 10890044
TI  - [The incidental sonographic finding of an unclear intraperitoneal space-occupying
      lesion].

PMID- 10890045
TI  - [Radiology of the esophagus. Basic knowledge].

PMID- 10890046
TI  - FMRFamide- and neurotensin-immunoreactive elements in the intestine of some
      polyclad and triclad flatworms (Turbellaria).
AB  - By means of immunohistochemistry with antisera to tetrapeptide FMRFamide and
      regulatory peptides neurotensin and calcitonin intestines of marine turbellarians
      Notoplana atomata, N. humilis (Polycladida) and Procerodes littoralis
      (Tricladida) were investigated. In all flatworms polymorphous cells and processes
      reacting with antibodies to FMRFamide and neurotensin but not with calcitonin
      were revealed. These cell elements are localized both in the epithelium and
      beneath it. FMRFamide-immunoreactive cells and processes of investigated
      turbellarians and neurotensin-immunoreactive elements in P. littoralis obviously
      belong to the nervous system, while intraepithelial neurotensin-immunoreactive
      cells of polyclads share some morphological features with endocrine-like cells.

PMID- 10890047
TI  - ["Nuclear secretion" in giant muscle cells of acanthocephala Filicollis anatis].
AB  - We have described the morphology of giant muscle cells, which are located in the
      praesoma root of young acanthocephala Filicollis anatis and are apparently
      similar with retinacular cells. The latter cells display signs which allow to
      suggest a nuclear secretion in them. The secreted material is supposed to
      participate in the formation of contractile elements.

PMID- 10890048
TI  - [The lack of G1/S arrest of teratocarcinoma F9 cells is determinated by
      degradation of cyclin-dependent kinases inhibitor p21waf1/cip1].
AB  - We have studied the ability of F9 teratocarcinoma cells to arrest in G1/S and
      G2/M checkpoints following gamma-irradiation. Wild-type p53 protein is rapidly
      accumulated in F9 cells after gamma-irradiation, however this is not followed by
      G1/S arrest; there is just a reversible delay of the cell cycle in G2/M. In order
      to elucidate the reasons of the lack of G1/S arrest in F9 cells we investigated
      the levels of regulatory cell cycle proteins: G1-cyclins, cyclin dependent
      kinases and kinase inhibitor p21WAF1/CIP1. We have shown that in spite of p53
      dependent activation of p21WAF1/CIP1 promoter, p21WAF1/CIP1 protein is not
      revealed by different polyclonal and monoclonal antibodies, either by
      immunoblotting or by immunofluorescent staining. However, when cells are treated
      with specific proteasome inhibitor lactacystin, p21WAF1/CIP1 protein is revealed.
      We therefore suggest that p21WAF1/CIP1 protein is subjected to proteasome
      degradation in F9 cells and probably the lack of G1/S arrest after gamma
      irradiation is due to this degradation. Thus, it is the combination of
      functionally active p53 with low level expression of p21WAF1/CIP1 that causes a
      short delay of the cell cycle progression in G2/M, rather than the G1-arrest
      after gamma-irradiation of F9 cells.

PMID- 10890049
TI  - [Cellular content of mixed saliva sediment in patients with chronic mucosal
      inflammation].
AB  - A comparative analysis was made of the saliva sediment cell composition in
      healthy patients and patients with chronic mucosal inflammation. Migration of
      leucocytes to the oral cavity was registered in patients with chronic
      inflammatory processes. A reliable increase in the number of epithelial cells
      with high degree of destruction was determined in saliva in addition to the
      appearance of cubic epithelial cells. These results indicate certain violation of
      epithelial reparation. It is proposed to use a quantitative analysis of saliva
      sediment for estimating functional conditions of mucosa.

PMID- 10890050
TI  - [Caldesmon inhibits formation of strongly bound myosin cross-bridges and
      activates an ability of weakly bound cross-bridges to transform actin monomers to
      the off-conformation].
AB  - The effect of caldesmon and its actin-binding C-terminal 35 kDa fragment on
      conformational alterations of actin in a muscle fiber at relaxation, rigor and at
      simulation of strong and weak binding of myosin heads to actin was studied by
      polarizational fluorimetry technique. The strong and weak binding forms were
      mimicked during binding of F-actin of ghost muscle fibers to myosin subfragment-1
      modified with NEM (NEM-S1) or pPDM (pPDM-S1), respectively. As a test for
      alterations in actin conformation, changes in orientation and mobility of a
      fluorescent probe, TRITC-phalloidin, bound specifically to F-actin were used. The
      results obtained have shown that during transition of the muscle fiber from the
      relaxed state into the rigor and during binding of actin filaments to NEM-S1,
      changes of polarization parameters take place, which are characteristic of
      formation between actin and myosin of the strong binding and of transformation of
      actin subunits from the "turned-off" (inactive) to the "turned-on" (active)
      conformation. Binding of pPDM-S1 to actin and relaxation of the muscle fiber are
      accompanied, on the contrary, by the changes of orientation and of the
      fluorescent probe mobility, which are typical of formation of the weak ("non
      force-producing") form of actin-myosin binding and of transformation of actin
      subunits from the active conformation into the inactive one. Caldesmon and its C
      terminal fragment markedly inhibit formation of the strong binding at rigor and
      activate transition of actin monomers to the switched off conformation at
      relaxation of muscle fiber. In parallel experiments, these regulatory proteins
      have been shown to inhibit an active force developed at the transition of a
      muscle fiber from relaxation to rigor. Besides, caldesmon and its fragment
      decrease the rate of actin filament sliding over myosin in an in vitro motility
      assay. Caldesmon is suggested to regulate the smooth muscle contraction in an
      allosterical manner. The alterations in actin conformation inhibit formation of
      strong binding of myosin cross bridges to actin and activate the ability of
      weakly bound cross bridges to switch actin monomers from the "on" to the "off"
      conformation.

PMID- 10890051
TI  - [Maintenance of torsional tension in DNA of transactivated genes during the cell
      cycle].
AB  - Changes in DNA topology during the cell cycle of murine fibroblasts in vitro were
      studied by microfluorometric method. At interphase stage, 21% of DNA were found
      to be torsionally stressed and hypersensitive to the relaxing activity of DNAase
      I. This DNA is presumably transcriptionally active. At metaphase stage, about 75%
      of DNA are under torsional stress with low sensitivity to DNAase I. After
      cytokinesis, one half of the stressed DNA relaxes, the other half of DNA remains
      under the stress. Later, one hour after cytokinesis, the stressed DNA attains
      hypersensitivity to DNAase I and remains hypersensitive during interphase. Taking
      into account that the cells in vitro steady maintain some domains of torsionally
      stressed DNA during the whole cell cycle, we suppose that these DNA domains
      contain genes, activated to transcription after mitosis. This may mean that the
      torsional stress preserved after mitosis is necessary for activation of the
      genes, which were active at the previous interphase stage.

PMID- 10890052
TI  - [Activation of nucleolar DNA and ribosome biosynthesis in hepatocytes under the
      effect of glucocorticoids and high density lipoproteins].
AB  - The structural bases of cooperative effect of glucocorticoids and HDL brings
      about the activation of protein biosynthesis in hepatocytes. Using surviving rat
      liver it was shown that these two compounds together activate the gene expression
      which was indicated by increased 3H-uridine incorporation into the total RNA
      pool. The enhanced incorporation of 14C-leucine into proteins in these
      experiments confirms protein biosynthesis acceleration. With the use of liver
      perfusion technique it was morphologically demonstrated that the earliest changes
      in hepatocyte genome take place in nucleoli. The increase of nucleolar dimensions
      and granular component reflects the activation of ribosomal precursors synthesis.
      Considerable number of ribosomes in the hepatocyte perinuclear space indicates
      their active transport across the numerous nuclear membrane pores into the
      cytoplasm. In the first place and more prominently in hepatocytes the protein
      synthesis "for export" is stimulated, which was proved by the dynamics of
      ribosome accumulation on the membranes of endoplasmic reticulum according the
      perfusion duration. The kupffer cells play a significant role in HDL transcytosis
      and in the realization of their cooperative effect with glucocorticoids.

PMID- 10890054
TI  - [The study of chromatin and chromosome structure on preparations of interphase
      nucleus derivatives resulting from nuclear wall removal.III Structural
      heterogeneity of chromatin and argyrophilic zone of the nucleolus in stretched
      membrane-free nuclei and chromatin bodies from human peripheral lymphocytes].
AB  - Viewed by light microscopy, the majority of lymphocytes in smears of human
      peripheral blood display a deep staining (with any chromatin- or DNA-specific
      dye) of the nucleus consisting of densely aggregated chromatin in addition to one
      or several small nucleoli with a dot- or spot-like argyrophilic zone.
      Amembraneous nuclei and "free chromatin" structures were isolated from intact
      lymphocytes gently treated with Triton X-100. Surface stretching of both these
      nuclei and structures, shortly fixed in methanol--glacial acetic acid (3:1),
      resulted in spatial separation of thin and thick chromatin or argyrophilic
      fibres, nucleoli, intranuclear bodies, polymorphous aggregations of chromatin or
      argyrophilic fibres and incidentally observed splitted or beaded thick chromatin
      fibres and the chromocenter. The light microscopic pattern of chromatin fibres of
      stretched amembraneous nuclei, isolated from peripheral lymphocytes, well
      compares with that of deconvolved images of intact lymphocyte nucleus obtained
      with optical tomography.

PMID- 10890053
TI  - [Reciprocal modulation of regulatory action of prolactin and somatotropin on DNA
      synthesis in granulosa cells of cows].
AB  - A comparative analysis of the individual and joint influence of bovine prolactin
      (BPRL) and bovine somatotropin (BST) on DNA synthesis in cultured bovine
      granulosa cells from follicles of 3-5 mm in diameter was conducted, and a
      possibility for regulation of BPRL binding to receptors on the cells by BST was
      examined. Despite a unidirectional growth-promoting action of BPRL and BST on
      granulosa cells, their joint mitogenic effect on the cells was not additive at
      low concentrations of BPRL. The addition of BST to the culture medium did not
      alter the biphasic character of dependence of DNA synthesis in the cells on BPRL
      concentration, but increased the maximum effective concentration of the latter.
      When culturing granulosa cells with BST, the absence of its influence on the
      level of BPRL specific binding to the cells was shown. This fact suggests that
      BST modulating action on the mitogenic effect of BPRL is not a result of a change
      in the number of free receptors for PRL on granulosa cells. The results obtained
      are discussed in relation to the notion of similarity of receptor functional
      properties and intracellular signal ways for PRL and ST.

PMID- 10890055
TI  - [The study of chromatin and chromosome structure on preparations of interphase
      nucleus derivatives resulting from nuclear wall removal. IV. Structural
      heterogeneity of stretched chromatin in membrane-free cell nuclei from human
      peripheral lymphocytes].
AB  - Densely aggregated chromatin of mature human or animal peripheral lymphocytes is
      inaccessible for structural investigation on preparations of both intact cell and
      conventionally spread chromatin. Giemsa- and DAPI-positive "free chromatin"
      structures, in addition to amembraneous nuclei, were isolated from intact
      lymphocytes gently treated with Triton-X-100. Surface stretching of both these
      nuclei and structures, shortly fixed in methanol-glacial acetic acid (3:1),
      revealed three main types of these "free chromatin" structures: dense chromatin
      structures (DCS), loose chromatin structures (LCS) and nuclear spreads (NS). The
      share of each nuclear derivative may be shifted by changing either detergent
      concentration and(or) the time of incubation in detergent solution. Each DSC
      consists of condensed "residual" nucleus, similar in from and size with an intact
      lymphocyte nucleus, and involves 1-15 uni- or olygonemic chromatin sprouts of
      different length. LSC contain heterogeneously loosened spindle-shape or drop-like
      nuclei, being several times longer and wider than DCS-nuclei, and 1-3 long uni-
      or olygonemic chromatin tail-pieces and incidentally observed lateral chromatin
      sprouts. The majority of LCS contain either a chromocenter of different number of
      end-to-end associated spindle-shape domains of condensed chromatin. The latter
      reached 2-5 x 1.5 microns being cross-striated or spiral in structure. NS
      represent spread chromatin fibrillar structures varying from 150 to 500 microns
      in length and from 1.5 to almost 50 microns in width. NS consist of 0.3-0.4
      micron smooth and 0.4-0.8 micron beaded chromatin fibres. Thin fibres produce web
      like domains of NS. and thick fibres form olygonemic bundles or end-to-end
      association of unit chromatin fibres within NS. Some portion of thick unit fibres
      of NS gave rise to local splitting into two thin fibres with a similar bead
      patterns. Thick argyrophilic fibers of the nucleolus also displayed a beaded
      structure and commonly spread hand-in-hand with the basic chromatin fibre
      aggregations.

PMID- 10890056
TI  - [The specific blocks of heterochromatin on metaphase chromosomes of horse and
      Prjewalski horse detected by in situ digestion with restriction endonucleases].
AB  - Restriction endonuclease in situ digestion of metaphase chromosomes gives an
      opportunity to reveal strips with different structure within GC-rich pericentric
      heterochromatin of the domestic horse and the wild Przewalski horse. Blocks of
      heterochromatin, which are insensitive to HaeIII and brightly stained with
      chromomycin A3 after restriction enzyme digestion, are localized on the border
      with euchromatin in the majority of chromosomes of Equus caballus and E.
      przewalskii. In contrast to chromosome 5 of E. caballus, acrocentric chromosomes
      of E. prezewalskii which are homologous to this chromosome have RE-CMA-blocks. We
      discuss a possible nature of the specific heterochromatin, which is insensitive
      to restriction enzyme digestion, and its role in the karyotype evolution.

PMID- 10890057
TI  - [The reaction of endoplasmic reticulum of Mauthner cells of Xenopus laevis
      tadpoles in response to the partial denervation].
AB  - The structure of the Mauthner cells in Xenopus laevis tadpole was investigated by
      light- and electron microscopy in norm and after early unilateral enucleation. It
      was found that enucleation at early stages caused a delay in morphological
      development of the contralateral neurons during embryogenesis. We observed a
      decrease in size of the soma and nucleus and in the number of dendrites, a marked
      structural underdevelopment of the majority of cell organoids, as well as
      proliferation and hypertrophy of transversal cisternae in the contralateral
      Mauthner cells. The ipsilateral neurostructure remained normal in embryogenesis.
      The data obtained suggest the availability of some unknown powerful afferent
      contralateral input to Mauthner cells from the optical analyzer.

PMID- 10890058
TI  - [Aleksandr Nikolaevich Berkutov (1906-1992)].

PMID- 10890059
TI  - [The flowmetric assessment of the adequacy of carotid endarterectomy].
AB  - The authors made an analysis of ultrasonic flowmetry in 36 operations of carotid
      endarterectomy in 22 patients with stenosis of brachiocephalic arteries. After
      removal of atherosclerotic plaques the volumetric blood flow in carotid arteries
      increased from 65-260 ml/min up to 210-400 ml/min. No substantial difference was
      noted between the increase of blood flow after classical endarterectomy and after
      the formation of a new carotid bifurcation. Flowmetry allows the estimation of
      adequacy of vascular reconstruction and the choice of correct management of the
      patients at the postoperative period.

PMID- 10890060
TI  - [A 2-stage method for the surgical correction of calcified aortic stenosis in
      patients with an extreme degree of risk for an operation].
AB  - During the period of 1992-1998 the authors dealt with treatment of 32 patients
      with aortic stenosis under extreme risk of operation. All the patients were
      considered to be inoperable because of the severity of their state. At the first
      stage of operation the catheter balloon valvuloplasty (CBV) was performed for
      decompression of the left ventricle since it was the only possible variant at
      this stage of surgical treatment. Good results of CBV were obtained in 22
      patients which led to the possibility to perform the prosthetizing of the aortic
      valve in 13 patients within two months at an average. There were no lethal
      outcomes. Long-term results followed-up during 6 years were estimated as
      satisfactory.

PMID- 10890061
TI  - [The dislocation of the omentum into the right pleural cavity].
AB  - The author presents results of a topographo-anatomical investigation aimed at
      studying and proving the optimum way of dislocation of a greater omentum flap
      into the pleural cavity in order to improve processes of regeneration of the
      bronchus stump. A flap of the omentum with the saved right gastro-omental artery
      was used. The esophageal foramen of the diaphragm, right sternocostal triangle
      were considered as possible ways of dislocation as well as the artificially made
      foramina in the tendinous center of the right half of the diaphragm.

PMID- 10890062
TI  - [Gastric motility based on gastric impedance measurement data after truncal and
      combined vagotomies in duodenal ulcer].
AB  - The motor function of the stomach was investigated by the gastroimpedansometric
      method in 73 patients: 32 of them with ulcer of the duodenum before operation, 17
      -after truncal vagotomy and 13 after combined (anterior selective proximal and
      posterior truncal) vagotomy with Finney's pyloroplasty within the period from 4
      to 10 years. Motor activity in the cardial and antral parts and the stomach body
      was evaluated using the computer medical complex "Gastrolog" by the indicator of
      local motility and contraction rate. The indicator of local motility was reliably
      higher in patients with ulcer of the duodenum than in healthy subjects. At later
      terms after truncal vagotomy a normokinetic type of motor activity was noted in
      all parts of the stomach, the level of motility of the antral part being reliably
      higher after combined vagotomy with saved anterior Latarget's nerve (p < 0.01).

PMID- 10890063
TI  - [The possibilities for improving the surgical procedure in hemorrhaging
      gastroduodenal ulcer].
AB  - The article describes an original variant of treatment of patients with bleeding
      ulcer of the stomach or duodenum. A classification of surgical interventions is
      proposed depending on the time of performing the operation. Verification of
      unstable hemostasis with the help of a computer expert program in patients with
      arrested bleeding and performing preventive emergency operation led to less
      postoperative lethality.

PMID- 10890064
TI  - [The treatment in ulcerative hemorrhages in patients with liver cirrhosis and
      portal hypertension].
AB  - Treatment of 34 patients with bleedings from chronic gastroduodenal ulcers
      associated with cirrhosis of the liver and portal hypertension was analysed.
      Overall lethality was 41.2%, postoperative lethality was 41.7%. Temporary
      hemostasis due to a solution of Caprofen used during fibrogastroduodenoscopy
      allows the operation to be delayed and complex intensive therapy can be performed
      in patients with hepatic insufficiency. Control medical endoscopic investigations
      should be performed 4 and 12 hours after admission to the hospital of patients
      with sub- and decompensated cirrhosis of the liver with portal hypertension and
      symptoms of unstable hemostasis. The emergency and delayed operative treatment of
      patients with subcompensated hepatic insufficiency should include organ-saving
      operations such as vagotomy with pyloroplasty and/or dissection of the ulcer.
      Operation is indicated to patients with cirrhosis of the liver at the stage of
      decompensation but if they have evident reappearance of bleeding and in minimal
      volume. The attainment of final endoscopic hemostasis will allow to avoid
      surgical interventions intolerable for this category of patients.

PMID- 10890065
TI  - [An analysis of the immunity indices of patients with indurative diseases of the
      head of the pancreas].
AB  - Based on an analysis of dynamics of immunity indices the authors have revealed
      differences in the character of their changes in nontumoral and tumoral diseases
      and in relation to the stage of the malignant process. The optimal minimum of
      indices of the immunity status in indurative diseases of the pancreas head is
      proposed which is of significance for differential diagnosis and determination of
      resectability of the tumor.

PMID- 10890066
TI  - [Biotransplants from the dura mater in the reconstruction of the aorta and
      arteries].
AB  - The authors have analyzed results of using dura mater as a plastic material in
      1078 patients with occluding diseases of the aorta and major arteries. Immediate
      positive results were noted in 93.4% of the patients. Long-term results from 12
      months to 19 years were studied in 683 patients.

PMID- 10890067
TI  - [The causes of complications and mortality in acute diseases of the abdominal
      organs].
AB  - A retrospective analysis of 854 case histories of patients who died in surgical
      hospitals of Orenburg Province from 1996 till 1998 has shown that 67% of the
      patients had infectious complications including 32.5% of suppurations of the
      postoperative wounds. Other causes of complications and lethality were
      established. Main ways to reduce their amount are determined.

PMID- 10890068
TI  - [Sodium hypochlorite in the treatment of the suppurative-septic complications in
      patients with strangulated hernias].
AB  - The article presents an analysis of surgical treatment of 2155 patients with
      incarcerated hernias of the anterior abdominal wall. Pyo-septic complications
      took place in 24.3%. A comparison of results of treatment by traditional methods
      with those using solution of sodium hypochlorite (indirect electrochemical
      oxidation of blood) has shown that in the group of patient treated with sodium
      hypochlorite lethality was reduced from (18.8 +/- 0.2)% to (11.2 +/- 0.2)%, the
      amount of suppuration of the operative wound was 1.8 times less and the average
      number of bed-days was (4.5 +/- 0.2) less.

PMID- 10890069
TI  - [A method for the surgical treatment of patients with chronic postoperative
      osteomyelitis of the sternum].
AB  - The authors share their experiences with diagnosing and surgical treatment of
      chronic postoperative osteomyelitis of sternum developed in 36 patients after
      operations on the heart, lungs and organs of mediastinum. The purulent process
      can be liquidated in all the patients due to performing saving resection of the
      sternum and plasty of the bone defect with local tissues, application of a gauze
      cotton roll pressing the subcutaneous fat into the bone defects formed after
      treatment of the affected portions of the sternum, administration of antibiotics
      according to sensitivity of the microflora.

PMID- 10890070
TI  - [The use of late temporary bronchial occlusion in the combined treatment of
      patients with acute suppurative lung abscesses].
AB  - The article presents results of late temporary occlusion of bronchi for
      prevention of chronicalization of the inflammatory process in 34 patients with
      acute purulent abscesses of the lungs. Formation of the dry residual cavity with
      the diameter of 2 cm and more was taken as an indication for such intervention.
      As a result of the treatment complete recovery was noted in 18 patients (52.9%),
      the state of 13 patients (38.2%) was improved, 3 patients (8.8%) had no effect.
      It was found that late temporary occlusion of the bronchi in combination with
      transdrainage vacuum aspiration made the effectiveness of conservative therapy
      for lung abscesses higher and reliably increased the amount of completely
      recovered patients.

PMID- 10890071
TI  - [The immune status and hemorheological indices in patients with an amebic liver
      abscess].
AB  - The immune status and hemorheological indices were studied in 95 patients with
      amebic abscess of the liver. Changes in the immune status and hemorheological
      indices were detected according to the clinical course of the disease. In cases
      of complications appearing during the disease the patients needed
      immunostimulating therapy and administration of desaggregants. Drainage of the
      thoracic lymphatic duct is thought by the authors to be a necessary component of
      treatment while performing massive infusion therapy and adequate recovery of the
      loss of blood proteins.

PMID- 10890072
TI  - [Programmed irrigation and drainage in the treatment of patients with a local
      soft-tissue suppurative infection].
AB  - Treatment of 92 patients aged from 18 to 69 years with abscesses and phlegmons of
      soft tissues included programmed irrigation and drainage. Apparatuses with two
      level programs were used. It was shown that programmed irrigation and drainage
      allowed microbial dissemination by wash liquid to be decreased to 10 colony
      forming units per 1 ml during 3 days. This term can be shortened to 1 day when
      using the program of intensive irrigation and drainage (more than 200 cycles
      during the first days after operation) and when intraoperative treatment with a
      beating jet of liquid is used in combination with curettage and vacuuming.

PMID- 10890073
TI  - [The effect of different methods of photohemotherapy on the rheological
      properties of the blood in patients with ischemic heart disease].
AB  - The authors made an analysis of results of examination of 41 patients with
      ischemic heart disease treated by the standard medicamentous therapy and when
      using different methods of photohemotherapy against its background. It was
      established that medicamentous therapy during 2 weeks failed to result in a
      substantial improvement of rheological properties of blood, while its combination
      with photohemotherapy could give a considerable positive effect coinciding with
      clinical improvement of the patient's state. Shorter terms are required to
      correct hemorheological indices when autotransfusions of photomodified blood are
      used.

PMID- 10890074
TI  - [Catheterization of the subclavian vein in patients with combined trauma in
      emergency situations].
AB  - The authors describe a simplified method of catheterization of the subclavian
      vein available in all medical institutions and in any situation.

PMID- 10890075
TI  - [The use of adaptive-repositioning apparatus for the closing of granulating soft
      tissue wounds].
AB  - The authors propose a new method of closing granulating wounds by attaching its
      edges with the help of an adaptation-reposition apparatus. This method was used
      in treatment of 53 patients with granulating wounds of different localization.
      Good results were noted in 88.7% and satisfactory ones in 11.3%. The method was
      shown to be highly efficient as compared with the control group.

PMID- 10890076
TI  - [The fixed omentum syndrome].
AB  - Ten cases of the fixed omentum syndrome which appeared in women operated on
      organs of the small pelvis are discussed. The cause of adhesions of the greater
      omentum and the parietal peritoneum and internal organs was the operative trauma
      in combination with inflammatory alterations of the peritoneum. The surgical
      treatment consisted in the division of adhesions of the greater omentum,
      resection of the omentum portion being fulfilled in cases of its cicatricial
      alterations. Complete healing was noted in all the patients.

PMID- 10890077
TI  - [The possibilities for preventing adhesive disease after appendectomy].
AB  - The authors have developed a method for influencing the altered peritoneum in the
      area of the inflammation focus by insufflation of medical aerosol at the
      postoperative period for quicker reestablishment of integrity and physiological
      function of its mesothelium and fibrinolytic activity which allows the
      probability of forming commissures in patients after appendectomy to be reduced.
      Long-term follow-up (up to 3 years) of 61 patients operated upon by the proposed
      method showed that in 59 of then the results were excellent and good.

PMID- 10890078
TI  - [The initial trial of the clinical use of FK-1 glue in surgical interventions].
AB  - The article presents results of a comparative clinical trial of the preparation
      "fibrinous glue" (FK-1) and "Beriplast" in operations on the lungs for
      hermetization of the wound and the lung as well as in reconstructive plastic
      gynecological operations. Intraoperative hermetization in operations on the lungs
      was obtained in 67% of the cases when using "FK-1" and in 64% with "Beriplast".
      In all the cases the lung was spread during 12 hours after operation. The visual
      intraoperative assessment of using "FK-1" and control laparoscopy on the 4th-5th
      days after operation showed its good effect in gynecological procedures. Clinical
      trials of the new domestic fibrinous glue "FK-1" in surgical and gynecological
      clinics confirmed its high medical effectiveness.

PMID- 10890079
TI  - [Metachronous tumors of the parathyroid and thymus glands in a young female
      patient].

PMID- 10890080
TI  - [Carcinoids of the small intestine].

PMID- 10890081
TI  - [The ultrasonic diagnosis of biliary ileus].

PMID- 10890083
TI  - [The basic principles of treating patients with chronic osteomyelitis of the long
      bones].
AB  - Experiences with surgical treatment of 269 patients with chronic osteomyelitis of
      long bones based on the principles of active surgical treatment of purulent
      wounds were summarized. Certain aspects of surgical treatment of patients with
      chronic osteomyelitis were revised and supplemented. Different variants of
      surgical treatment of the osteomyelitis focus were shown depending on the volume
      and character of the injury and the methods of plastic substitution of defects of
      the bones and soft tissues. Main principles of antibacterial therapy for chronic
      osteomyelitis are described.

PMID- 10890082
TI  - [The successful elimination of complications in the late postoperative period
      after an aortic-bifemoral bypass].

PMID- 10890084
TI  - [The objective assessment of the activities of the hospital surgeon].

PMID- 10890085
TI  - [German Fedorovich Tseidler (1861-1940)].

PMID- 10890086
TI  - [Vil'gel'm Adol'fovich Shaak (1886-1957)].

PMID- 10890087
TI  - [Valentin Mikhailovich Sitenko (1911-1996)].

PMID- 10890088
TI  - [The diagnosis and treatment of ventilator-associated pneumonias].

PMID- 10890089
TI  - [Destructive pancreatitis: the current state of the problem].

PMID- 10890090
TI  - [Transplantation of the pancreas].

PMID- 10890091
TI  - [Sergei Romanovich Mirotvortsev (1878-1949)].

PMID- 10890092
TI  - [Internal biliary fistulas of cholelithic origin].
AB  - The investigations performed have established that the cause of formation of
      internal biliary fistulas in 162 patents was cholelithiasis in combination with
      obstruction of the bile tracts, purulent cholelithiasis, cholangiolitic abscesses
      of the liver, pancreatitis and cholelithic ileus. The operation of choice is
      thought to be cholecystectomy, removal of the stones from the bile ducts,
      reestablishment of the major bile outflow, liquidation of the pathological
      anastomosis and suturing the hollow organ defect. Fibrogastroduodenoscopy,
      retrograde cholangiopancreatography and percutaneous transhepatic cholangiography
      are the most informative methods of diagnosing the internal biliary fistulas. The
      postoperative lethality was 17.2%.

PMID- 10890093
TI  - [Immune and nonimmune variants of acute pancreatitis].
AB  - The article gives an analysis of humoral immunity to structural and secretory
      components of the pancreas in acute pancreatitis. Based on the distinctions
      revealed the authors determined two variants of the disease--the immune and
      nonimmune variants which is of great significance in diagnostics and treatment of
      acute pancreatitis, for the administration of immunocorrecting medicines in
      particular.

PMID- 10890094
TI  - [Effects of hemosplenic perfusion on the state of humoral immunity in suppurative
      septic complications in emergency abdominal surgery].
AB  - Hemosplenoperfusion (HSP) through the donor porcine spleen was used in complex
      treatment of 75 patients aged from 16 to 75 with pyo-septic complications of
      diseases and traumas of the abdominal cavity. The influence of HSP on the state
      of humoral immunity was estimated by the level of antibacterial antibodies to the
      antigens of E. coli, Ps. aeruginosa, Pr. mirabilis, St. aureus, Bact. fragilis,
      Bact. bifidum and antiendotoxin antibodies to glycolipid S. Minnesota RE 595,
      general cortical part of the lipopolysaccharide of Gram-negative bacteria. The
      use of HPS promoted the resolving of endogenous intoxication, elevation of the
      strain of humoral antibacterial immunity and is characterized by a reliable
      increase of the level of antibacterial antibodies in the dynamics of treatment.

PMID- 10890095
TI  - [New approach to the classification of traumatic amputation of hand fragments].
AB  - It was shown that of the greatest significance for early results of microsurgical
      digit and hand segment replantations were the completeness, mechanism and the
      level of the amputation. The criteria used for the classification of traumas are
      described in detail. Results of treatment of 154 patients operated upon for
      replantation of 184 segments of the hand (217 radiuses of the hand) are
      presented.

PMID- 10890096
TI  - [Use of gas-current coagulation in the local treatment of gunshot wounds].
AB  - The article is devoted to the using of gas-current coagulation for treatment of
      gunshot wounds in experiment. A new technology of physical action on biological
      tissues allows the simultaneous performing of hemostasis, sterilization of the
      wound surface, dissection and evaporation of the tissue. The isolation of the
      wound surface from unfavorable aggressive factors of the environment due to the
      layer of thermal necrosis results in shortening the 1 phase of the wound process
      and in earlier development of its second phase. Healing proceeds by the type of
      productive inflammation. The use of the gas-current coagulation during the
      performing of the primary surgical treatment of gunshot wounds allowed to
      considerably reduce its time, improve its quality, substantially lessen the
      amount of infectious complications, considerably improve the indices of the wound
      process and results of treatment.

PMID- 10890097
TI  - [Causes of complications and fatal outcome after combat gunshot wounds of the
      internal organs].
AB  - Under examination there were 110 wounded with battle gunshot injuries of organs
      of the abdominal cavity. Among them there were 14 patients with thoracoabdominal
      wounds. Injuries of the internal and other organs were diagnosed in 39 wounded.
      Ten patients had injuries of the internal organs and upper extremity, 11 patients
      had injuries of the lower extremity, 4 patients had wounds in the pelvic area, 7-
      of the trunk, 2--of the skull and face, 5--of the chest. Postoperative
      complications developed in 28%. Relaparotomy was performed in 13.6% of the
      patients. Postoperative lethality was 15.3%.

PMID- 10890098
TI  - [Neoplasms of the genitalia in young girls].
AB  - The results of an analysis of 197 clinical examinations of young girls aged from
      8 to 19 years with neoplasms of the genitals have shown that ovarian tumors made
      98.5% of the cases. The benign forms prevailed over malignant ones. The
      distribution of the ovarian tumors in the girls by the histotype considerably
      differs from that in adult women with the same tumors. Only 24.7% of the true
      ovarian tumors had the epithelial forms, while 75.3% were nonepithelial and 80%
      of them represented germinal tumors. An analysis of literature data and personal
      observations prove high sensitivity of malignant tumors of the genitals in
      puberty girls to chemotherapy which allows the organ-saving operations to be
      performed. The timely diagnosis of genital tumors in girls based on the well
      organized children and adolescent gynecological service can promise the
      optimistic prognosis.

PMID- 10890099
TI  - [Reconstructive jejunogastroplasty].
AB  - A method of reduodenization providing the formation of the invagination-valvular
      jejunoduodenal and sphinctero-valvular esophagojejunoanastomoses has been
      developed for treatment of patients with postgastroresectional disorders. The
      method allows the duodenum to be included in the process of digestion by means of
      creation of the small intestine transplant from the efferent intestinal loop. For
      prevention of regurgitation at the remote postoperative period the invagination
      valvular jejunoduodenal anastomosis was formed by the authors method. Observation
      of the patients during 5 years following the operation showed good functional
      results of the operation proposed.

PMID- 10890100
TI  - [Causes of unsuccessful attempts of laparoscopic cholecystectomy].
AB  - Based on an analysis of personal observations and literature data the authors
      made an analysis of the frequency and causes of unsuccessful laparoscopic
      cholecystectomy (LChE) resulting in laparotomy (conversion). LChE was successful
      in 217 of 233 operations. In 16 patients (6.9%) conversion was performed.
      According to the summary data of the literature on 150,000 cases of LChE the
      frequency of conversion was from 0.9 to 18%. The frequency of conversions was
      found to depend on the strategy of determining the indications for LChE and on
      the level of technological maintenance of operations. Three groups of the causes
      of conversion were set up on the basis of an analysis of publications about 498
      cases of unsuccessful attempts of LChE and 16 personal observations:
      pathomorphological (393--78.9%; 7--43.8%); iatrogenic (99--19.9%; 7--43.8%) and
      technico-instrumental (6--1.2%; 2--12.4%). The pathomorphological causes lead to
      noncomplicated conversion and indicate to the limited use of LChE for the
      concrete patients. The iatrogenic and technico-instrumental causes appear all of
      a sudden and require emergent laparotomy. So the total frequency of conversion
      can not be a criterion for the assessment of complications after LChE. It is
      expedient to make a special analysis of the causes of transition to laparotomy
      and to distinguish the complicated and not complicated conversion.

PMID- 10890101
TI  - [Complications of implantation of the cava filter "Reptela"].
AB  - The article describes a complication resulting from the implantation of a cava
      filter for roentgen endovascular prophylactics of thromboembolism of the
      pulmonary artery (REPTEPA) to a 68 years old woman with recurring thromboembolism
      of the pulmonary artery, floating thrombus of the right iliac vein. An attempt to
      disconnect the cava-filter from the applicator after implantation proved to be
      unsuccessful which was followed by urgent operation: marginal resection of the
      vena cava inferior with the cava-filter, suture of the vein, cava plication. The
      nearest postoperative period was complicated by thrombosis of the plication zone.
      The examination in 6 months has shown the formation of the syndrome of the vena
      cava inferior.

PMID- 10890102
TI  - [Mechanisms of the optimization of oxygen metabolism under the effects of mafusol
      and mildronate during emergency implantation of hip prosthesis].
AB  - The results of using antihypoxants Mafusol and Mildronate in the course of
      emergency endoprosthesis of the hip joint were analyzed in 41 patients at the age
      of (80.5 +/- 5.6) years with fractures of the proximal part of the femoral bone.
      The authors noted optimization of the organism oxygen budget under the influence
      of the drugs, its physiological mechanisms being deciphered. The protective
      properties of these drugs manifested themselves in lower consumption of oxygen by
      the tissues with greater possibilities of its release by oxyhemoglobin as well as
      in the lessening of intrapulmonary shunting and prevention of the development of
      metabolic acidosis.

PMID- 10890104
TI  - [Removable draining aponeurotic and muscular-aponeurotic sutures in the
      prevention of suppuration of laparotomy wounds].
AB  - Clinico-instrumental investigations and experimental studying of the regeneration
      of laparotomy wounds sutured by removable draining aponeurotic and muscular
      aponeurotic sutures have shown less pronounced course of aseptic inflammation in
      the wounds. It has been established that the removable aponeurotic sutures
      substantially decrease the frequency of postoperative suppurations of laparotomy
      wounds in patients operated on the colon mainly for colorectal carcinoma. The
      original authors' sutures provide the formation of a cicatrix of the laparotomy
      wound by the 20th day of the postoperative period and completely prevent the
      appearance of ligature fistulas.

PMID- 10890103
TI  - [Endoscopic intubation of the trachea in emergencies].
AB  - The article presents the results of performing endoscopic intubation of the
      trachea under emergency situations in patients and victims of traumatic and pyo
      inflammatory alterations of organs and tissue of the neck. The technique of the
      trachea intubation is described. It was noted that in such patients there appear
      serious problems during the intubation of the trachea by the method of direct
      laryngoscopy which are due to considerable disturbances of the anatomo
      topographic interrelations of the organs, marked edema of the tissues and by the
      presence of the pathological content in the lumen of the oro- and laryngopharynx.
      The trachea intubation performed under the control of vision with the help of a
      bronchofibroscope allows to avoid additional traumatization of the tissue of the
      oro- and laryngopharynx, to rapidly introduce the endotracheal tube into the
      trachea without hypoxia, to perform sanitation of the oral cavity, pharynx and
      the tracheobronchial tree.

PMID- 10890105
TI  - [Possibilities of prognostication of suppurative-inflammatory complications of
      surgical treatment of patients with nonrecurrent postoperative ventral hernia].
AB  - On the basis of the data of a retrospective investigation of 541 patients with
      nonrecurrent noncomplicated postoperative ventral hernia the criteria of
      prognosis of pyo-inflammatory complications in the operative wound after
      liquidation of the abdominal wall defect became more exact and quantitated. It
      was established that 18 criteria can be used for prognosis, 14 of them--before
      operation. During the operative procedure it can be possible to make the
      prognosis more exact with the intraoperative findings taken into account. Among
      them of special significance are 4 prognostic criteria: multichamber hernial sac,
      commissural process in the abdominal cavity, the fact of separation of the
      commissures and possible perforation of the hollow organ. The efficiency of the
      program was 80%. The approbation of the program has shown that prognosis of the
      development of pyo-inflammatory complications must be made on the basis of both
      the preoperative and intraoperative criteria. It allows to reliably reduce the
      amount of postoperative pyo-inflammatory complications from 8.6% (retrospective
      data) to 5.2% (prospective data).

PMID- 10890106
TI  - [Use of neural network computer technology in the determination of therapeutic
      strategy in patients with stomach and duodenal ulcer].
AB  - The authors present the expert neural network programmed complex "Axon" allowing
      the prognosis of the course of ulcer disease of the stomach and duodenum to be
      made. On the basis of the prognosis obtained certain medical strategy can be
      recommended. The neural network in which the data of treatment of 909 patients
      with ulcer disease of the stomach and duodenum had been introduced was taken as a
      basis of the complex. The program is registered in the Russian copyright agency
      for PC programs, data base and topologies of integrated circuits. The authors
      consider that the approach proposed will allow the correct medical policy to be
      chosen which can lead to better results of treatment of patients with ulcer
      disease and thus the 100 years long contradictions between different specialists
      in determining medical policy for such category of patients will be overcome.

PMID- 10890107
TI  - [Surgical treatment of post-infarction aneurysms using the tunneling method].
AB  - The work is devoted to the development of new methods of surgical treatment of
      postinfarction aneurysms. An experience with performing 25 operations of
      tunneling the myocardium of the left ventricle and aneurysmoplasty has shown the
      possibility of performing such operations in patients when it is impossible to
      perform the direct aortocoronary shunting and aneurysmectomy under conditions of
      extracorporeal circulation.

PMID- 10890108
TI  - [Bronchoscopy in complex examination and treatment of patients with lung
      abscess].
AB  - Lung abscess was diagnosed during a complex examination in 115 patients. All the
      patients had local treatment through the bronchoscope. Cleansing of the abscess
      cavity takes place 1,3 times quicker in the patients who were given laser
      irradiation in addition to sanitation bronchoscopy or to whom immunomodulators
      and antibiotics were introduced lymphotropically intrabronchially, than in those
      with usual sanitation. The administration of 20 ml of glycerol in the abscess
      cavity allowed cleansing of the cavity to be 2-3 times quicker.

PMID- 10890109
TI  - [Transillumination hemodynamic and motility monitoring of patients with stomach
      ulcer].
AB  - The transillumination hemomotordynamic monitoring of patients with ulcer disease
      of the stomach has been developed. Hemomotordynamics in the zone of the suture
      stria, ulcerogenic zone and pyloro-antral portion of the stomach were
      investigated during operation for prevention of ischemic and motor complications
      as well as for determination of the resection borders. In the postoperative
      period the transillumination hemomotordynamic monitoring allows determination of
      the time of recovery of the operated stomach motility for the following
      transmission of the patient to enteral feeding and prevention of motor and
      hemodynamic complications using pharmacological correction.

PMID- 10890110
TI  - [Perspectives of using radiofrequency surgery in operations on the major duodenal
      papilla].
AB  - The article presents the results of an experimental study of the possibility of
      using radiofrequency surgery for performing papillosphincterotomy. A generator of
      radiowaves of a high frequency range was used for the generation of the
      electromagnetic field, which when acting upon the living tissues makes a cut and
      destruction of the tissue. The experiment was made in 20 dogs divided into two
      groups for acute and chronic experiments. In the group of chronic experiments the
      dogs were exterminated on the 7, 14, 21 and 35th days after operations. The area
      of the influence in all the periods of the experiment was investigated
      histologically. Significant advantages of the given method as compared with the
      traditional ones were revealed.

PMID- 10890111
TI  - [Foreign bodies of the rectum].
AB  - During the 22 years period there were 26 patients (23 men and 3 women) aged from
      18 to 71 with foreign bodies in the rectum introduced through the anal canal. The
      main causes of the appearance of foreign bodies in the rectum were anal
      masturbation (in 12 patients) and forced introduction of the objects by other
      people (in 10 patients). Among the foreign bodies prevailing were plastic and
      glass bottles, cucumbers and carrots, wooden and rubber objects in the from of
      the phallus. Typical were large sizes of the most objects introduced (the
      diametrical size more than 6 cm and the length more than 15 cm) which was
      responsible for the development of complications and made the removal difficult.
      The symptoms of the presence of foreign bodies in the rectum were determined as
      well as the optimum methods of diagnosis. A classification of rectal foreign
      bodies is proposed for the solution of medico-tactical tasks. The transcanal
      removal of the foreign bodies was fulfilled in 23 patients. The standardized
      technique of the transcanal removal of the objects is thought by the authors to
      include 10 principal propositions. Open operative interventions (removal of the
      foreign body, suturing the rupture, drainage of the abdominal cavity or of the
      perirectal space, sigmostomy) were performed in 4 patients with penetrating
      injuries of the rectum wall. The results of the treatment including removal of
      all foreign bodies were good, without lethal outcomes.

PMID- 10890112
TI  - [Atypical cases of gastric bleeding].

PMID- 10890113
TI  - [Alveolar Echinococcus (alveococcus) of the kidney].

PMID- 10890114
TI  - [A rare case of severe generalized myasthenia against a background of pregnancy].

PMID- 10890115
TI  - [Nodulation of Meckel's diverticulum].

PMID- 10890116
TI  - [Results of the use of a new vascular prosthesis "Vitaflon" in patients with
      critical ischemia of the lower limbs].
AB  - A new Russian vascular artificial prosthesis from porous PTFE ("Vitaflon") was
      used in 39 cases of different obliterative arteriopathy in the critical ischemia
      phase, moreover in 12 cases with foot gangrene. The diagnoses for all the
      patients (35 men, 4 women, average age 57.8 years) were made in accordance with
      the clinical data, arteriography and ultra-sound imaging. In 15 cases the cause
      of ischemia was thrombo-obliteration of the aorto-femoral and in 24 cases of the
      femoro-popliteal segments. The following bypass operations were made: aorto
      femoral graft implantation in 3 cases, ilio-femoral in 7 and ilio-popliteal in 2
      cases, extra-anatomical femoro-femoral bypass graft in 4 cases and axillo
      bifemoral in 1 case, femoro-popliteal above the knee bypass in 17 cases, in 2
      cases explant-profundi femoral, in 1 case popliteal-peroneal prosthesis and in 2
      cases profundoplasty. The postoperative period showed 1 graft thrombosis with a
      successful thrombectomy. In one case an infection of the femoro-femoral
      prosthesis was registered which was removed. In the long-term period up to 4
      years thrombosis was registered in 6 cases with femoro-popliteal and in 2 cases
      with ilio-popliteal and ilio-femoral bypass grafts. High limb amputation had to
      be done in 5 cases. During this period 8 patients died from the causes other than
      operation. 28 cases with working grafts were followed-up, they underwent duplex
      doppler investigation and in 4 cases arteriography. The first results showed
      excellent qualities of the new prosthesis which can be compared with those of the
      best similar models.

PMID- 10890117
TI  - [Gastroduodenal ulcer bleeding in patients with severe concomitant diseases].

PMID- 10890118
TI  - [Concerning the article by B.I. Miroshnikov i N.S. Chechurin, "Gastroduodenal
      ulcer bleeding in patients with severe concomitant diseases"].

PMID- 10890119
TI  - [Myocardial revascularization on a beating heart].

PMID- 10890120
TI  - [Stimulated angiogenesis: a new trend in the treatment of ischemic conditions].

PMID- 10890121
TI  - [Cochlear implants in children and adults].

PMID- 10890122
TI  - [Rehabilitation of hearing-impaired patients with cochlear implants: a review].
AB  - The aim of this paper is to provide an overview of the cochlear implant. The
      history of this entity is traced from the early development of implants,
      involving the stimulation of the hearing nerve, up to the currently available
      standard multichannel implants. The physiological background is also elucidated.
      A cochlear implant consists of an implantable portion which lies within the ear,
      and of parts that are worn externally on the body. Differences between the first
      implants and those now in use are as follows: transcutaneous information and
      energy transmission, the position of the electrode in the ear, and the
      configuration of the electrode. Differences between the currently available
      implants mainly concern the number of electrodes, speech coding strategies and
      the mode of electrode stimulation. Almost all of the most recent implants are
      equipped with electrodes that are implanted in the tympanic scale of the cochlea.

PMID- 10890123
TI  - [Cochlear implantation--the Viennese surgical technique].
AB  - The aim of the study was to report the current surgical procedure that has been
      established on the basis of about 200 implantations with the Combi 40/40+ implant
      system. The outstanding features of this procedure are the skin incision and the
      fact that the electrode can be inserted up to a depth of 34 mm into the cochlea.
      In order to provide better magnetic positioning of the external parts, a flap
      reducing technique may be required. For insertion we used a soft surgery method
      to preserve structures within the cochlea. In some cases we were able to inspect
      the cochlea with microendoscopes, which helped to prevent electrode kinking,
      since fibrous obliterations were found before the insertion. For electrode
      fixation in the mastoid cavity we used bone pate.

PMID- 10890124
TI  - [Intracochlear position of cochlear implant electrodes].
AB  - The insertion of cochlear implant electrodes in human temporal bones may be
      associated with the destruction of structures within the cochlea. The aim of this
      study was to measure such insertional trauma by means of histologic processing of
      implanted human temporal bones following implantation of a Combi 40/40+ electrode
      array (Med-El, Innsbruck). We implanted 6 human temporal bones with original
      electrodes (3 with Combi 40 and 3 with Combi 40+). In 4 bones Healon was used for
      electrode insertion. The histological investigation was performed after
      radiographic evaluation of the position of the electrode. For the histological
      procedure we used a technique which keeps the electrodes in position within the
      cochlea. In these slides we could clearly identify the electrodes in the tympanic
      scale. When inserted properly (point of first resistance) no trauma occurred in
      the basal portion of the cochlea and minimal trauma in the middle portion of the
      cochlea.

PMID- 10890125
TI  - [Preoperative imaging of the inner ear prior to the implantation of a
      multichannel cochlear implant using computed and MR technology].
AB  - CT and MRT are now standard examinations prior to insertion of a cochlear
      implant. Both methods have advantages and disadvantages in terms of discovering
      potentially pathological structures in the inner ear. The aim of this study was
      to evaluate the pros and cons of using CT and MRT before cochlear implantation.
      CT is usually performed using axial planigraphic planes. Like MRT, bone-specific
      CT is helpful in the diagnosis of congenital and acquired changes within the
      inner ear. Congenital defects in the meatus acusticus internus, the endolymphatic
      duct and sac, the cochlea and the vestibulum can be diagnosed and also
      quantified. Infectious morphologic changes can be seen on CT images in their
      terminal residual state (sclerotic tissue). However, acute inflammation and
      fibrotic tissue is not visible on CT. T2-specific MRT images are very fluid
      sensitive and play a major role in preoperative cochlear implant diagnosis. This
      examination demonstrates fluid within the peri- and enolymphatic cave and permits
      the diagnostician to determine whether congenital or acquired diseases have
      destroyed such fluid-filled cavities. In order to demonstrate pathological
      changes in the temporal bone and neural structures in the inner ear, MRT is the
      preferred method. Displaying the modiolus and the cochlear nerve is extremely
      important because, in their absence, a cochlear implantation may be contra
      indicated. MRT also demonstrates other neural structures such as the facial
      nerve. This information may be important for the surgeon, e.g. the state of the
      pneumatic system in the mastoid cavity (which is best visualised by bone-specific
      CT).

PMID- 10890126
TI  - [Speech discrimination in post-lingually deaf patients with cochlear implants].
AB  - The aim of this study was to measure the speech discrimination performance of
      postlingually deaf patients using the Combi 40/40+ cochlear implant (Med-El,
      Innsbruck). The speech perception performance of 37 adults was tested over a time
      span of three years. We used a standardised test battery comprising number,
      monosyllable, sentence, consonant and vowel discrimination tests. Testing was
      performed immediately after initial fitting and 1, 3, 5, 12, 24, and 36 months
      thereafter. The average correct answers for all tests were as follows: right
      after the implantation 29.1%, after 1 month 46.7%, after 3 months 53.9% after 1
      year 63.5% and after 3 years 68.5%. Some patients reached a number discrimination
      rate of 100%. The discrimination for monosyllables averaged 41.1% two years after
      implantation. The results demonstrated continuous improvement of speech
      perception, even after three years following implantation.

PMID- 10890127
TI  - [Hearing and speech discrimination scores of prelingually deaf children with
      cochlear implants].
AB  - The goal of this study is to report mean values of speech perception performance
      in prelingually deaf children who received a Combi 40/40+ cochlear implant.
      Thirty-one patients were included in the study. The time span ranged over 3
      years, during which time the Evaluation of Auditory Responses to Speech (EARS)
      test battery was used in the children. The EARS battery contains 4 measures of
      closed-set speech perception and 3 open-set tests. The mean test results
      exhibited steady improvement in all parts of the EARS test battery, even up to 3
      years post-implantation. The mean preoperative scores were 0.3%, increasing to
      92.3% at 36 months post-implantation for the best children. Results for the
      closed-set testing measures were most encouraging, with some children reaching
      fairly high levels of speech perception and achieving scores as high as 98.7% at
      the 36-month evaluation. The congenitally and prelingually deaf children in our
      study showed continuous improvement in both closed and open set speech perception
      following cochlear implantation, although individual variations in performance
      were noted.

PMID- 10890128
TI  - [Speech discrimination in noise for patients with cochlear implants].
AB  - The aim of the study was to evaluate the speech discrimination ability of
      postlingually deaf adults implanted with the Combi 40 cochlear implant in noise
      and to compare the results with the speech discrimination ability of patients
      provided with hearing aids. The 12-month postoperative hearing performance of 12
      consecutive patients was tested using a sentence discrimination test in quiet and
      noise. The results of the present study demonstrate that all patients obtained
      substantial benefit from their implants even in situations coupled with noise.
      The speech understanding of cochlea-implanted patients appears to be better than
      that of patients provided with hearing aids. Very high scores (mean, 40.2%) were
      achieved at a signal-noise ratio of 15 dB.

PMID- 10890129
TI  - [Preoperative diagnostic procedures before cochlear implantation].
AB  - About 200 patients are considered each year for cochlear implant recipiency. Only
      1/4 of these candidates actually receive an implant. The aim of the study is to
      discuss the preoperative procedure we use, which is aimed to exclude patients who
      would not benefit from an implant. A cochlear implant is an example of very
      expensive high-profile medical therapy, a single implant costing about 280,000
      Austrian schillings. The aim of the preoperative diagnostic procedure is to
      select the right patients, with a view to providing the best audiologic outcome.
      During the past 20 years, important parameters have been identified to determine
      suitable patients. Candidates for a cochlear implant are infants and children
      (independent of the etiology of deafness or high-grade hearing loss), as well as
      postlingual deaf adults. Congenitally deaf adults or teenagers are considered
      unsuitable to receive an implant.

PMID- 10890130
TI  - [Postoperative imaging and evaluation of the electrode position and depth of
      insertion of multichannel cochlear implants by means of high-resolution computed
      tomography and conventional X-rays].
AB  - Following cochlear implantation, postoperative imaging of the electrode is very
      important in order to measure the depth of insertion and the position of the
      electrode, so that kinking and incorrect electrode placement can be clearly
      identified. The aim of this study was to outline the diagnostic value of CT and
      conventional X-ray for these parameters. For this purpose we obtained radiographs
      of patients who had received a cochlear implant. Computed tomography was
      performed by obtaining axial sections. For conventional X-ray we used digital
      imaging, utilising a modified Chausse III projection. The images were then rated
      according to electrode position, insertion depth and possible complications. We
      also measured the radiation dose using a dummy and evaluated the cost of each
      examination. Both examinations permit excellent identification of electrode
      position and insertion depth. However, the depth of insertion can be measured
      much more accurately by means of digital X-ray. The radiation dose of CT was 230
      times higher than that of conventional X-ray and the cost of CT 5 times that of
      digital X-ray.

PMID- 10890131
TI  - [Clinical utilization of magnetic resonance imaging for patients with cochlear
      implants].
AB  - To date, MR imaging is absolutely contraindicated in cochlear-implanted patients.
      The aim of this study is to document the potential value of MR imaging in such
      patients, without injurious or side effects and without technical device failure.
      After in vitro experimental testing, 25 cochlear implanted patients underwent
      MRI. Radiological evaluation was also possible. The use of 1-Tesla fast spin echo
      sequences minimised artifacts. All cochlear implants are still in working order;
      no changes in fitting data or a reduction in speech understanding were observed.
      MR helped to avoid other invasive medical procedures.

PMID- 10890132
TI  - [Cochlear implantation and auditory feedback].
AB  - The aim of the present study was to evaluate the short term effect of cochlear
      implantation on the fundamental frequency and the articulation of 13 patients.
      This investigation objectives for the first time the changes of fundamental
      frequency and articulation in cochlear implant patients. All postlingual deaf
      patients were provided with a Combi 40+ cochlear implant. Voice recording was
      performed pre- and three months post-implantation. The voice data was analyzed
      using the "X-Tool" software. The results show that 38% of the patients had a
      significant (p < 0.05) decrease of F0 mean three months after implantation. A
      postoperative decrease of F0 towards the normal range was observed generally in
      all patients. Spectographs pre- and post-implantation showed that the
      articulation improved already 3 months after partial restoration of auditory
      feedback. A large variability of F0 was noticed among the deaf subjects, but no
      correlation to the duration of deafness could be established.

PMID- 10890133
TI  - Malaria in Central Europe: fears and facts.

PMID- 10890134
TI  - [Noncompliance in organ transplantation: a review].
AB  - The effectiveness of medical treatment depends not only on the appropriateness of
      the treatment modality but also on the patient's compliance with the intended
      regimen. The consequences of failing to comply can be damaging and devastating
      for the individual patient and his/her family. Noncompliance also leads to waste
      in two areas: first, a reduction of the potential benefits of therapy, and
      second, the additional cost of treating the avoidable consequent morbidity. A
      dramatic example of the consequences of noncompliance with the treatment regimen
      concerns patients who have had organ transplants: life-long immunosuppression is
      a pre-requisite for good graft function, and noncompliance is often associated
      with the occurrence of late acute rejection episodes, graft loss, and death. Here
      it might be assumed that these patients constitute a highly motivated group, and
      that compliance would be high. Unfortunately, this is not the case: overall
      noncompliance rates vary from 20 to 50%. There is no systematic and comprehensive
      review of the literature on noncompliance and its consequences in organ
      transplant patients to date. This overview includes literature on heart, liver
      and kidney transplants in adult and paediatric transplant patients and addresses
      the following issues: preoperative behaviour patterns as predictors of
      postoperative compliance problems, compliance behaviour after transplantation,
      noncompliance and its relationship to organ loss and death, retransplantation
      outcome after graft loss due to noncompliance, reasons for postoperative
      noncompliance, and ways to promote compliance.

PMID- 10890135
TI  - Mefloquine concentration profiles during prophylactic dose regimens.
AB  - A pharmacokinetic study with (malaria) prophylactic doses of mefloquine
      hydrochloride was conducted in 12 healthy adult subjects (Caucasians), 6 females
      and 6 males, mean age 29.2 +/- 6.4 years, mean weight 70.6 +/- 13.4 kg. Doses of
      250 mg mefloquine were administered on days 0, 1, 7, 14, 21 and 28. Six subjects
      received a further 5 weekly doses of 250 mg mefloquine, the others 5 further
      weekly doses of 125 mg. After the third dose the protective threshold mefloquine
      concentration in blood plasma was achieved in all subjects. In female subjects,
      mean Cmin ss, Cmax ss and AUCd 0-35 were significantly higher than in males.
      After the fifth dose, mean Cmax in females reached 1692 ng/ml (4.48 mumol/l),
      equivalent to a high therapeutic concentration. This is apparently due to a
      generally lower body weight and a narrower volume of distribution in women.
      Adverse reactions were significantly more frequent in women than in men.
      Headache, anorexia, insomnia and vertigo were the most common side effects. The
      lesser tolerability of mefloquine in females may be due to the higher drug
      concentrations in this group. This may indicate the need for appropriate
      adjustment of the prophylactic dose regimen of mefloquine in females.

PMID- 10890136
TI  - A blinded, controlled trial of an ultrasound device as mosquito repellent.
AB  - Ultrasound emitting devices are used to repel mosquitoes. We tested the repelling
      properties of a commercially available ultrasound device in a domestic setting in
      Gabon. Devices emitting three different block frequencies ranging from 3 to 11
      kHz were tested in a paired, cross-over blinded and placebo controlled trial
      during eighteen nights in nine pairs of houses. A total of 7485 mosquitoes (10%
      Anopheles, 62% Culex, 27% Mansonia and 1% Aedes) were caught, 23 per house per
      night. There was no significant difference in landing rate between the houses
      with ultrasound device and the houses with placebo for any species of mosquito.
      Thus the ultrasound device used was not effective against mosquitoes in this
      strictly controlled trial.

PMID- 10890137
TI  - Effect of alcohol on growth of Plasmodium falciparum.
AB  - The effect of ethanol on the in vitro growth of the malaria parasite Plasmodium
      falciparum was investigated. 17 mM (0.08%) and 85 mM (0.39%) ethanol were added
      to parasite cultures and growth was determined for six days. A significant growth
      inhibition for both ethanol concentrations was observed on each day. It reached
      65% for 85 mM ethanol after six days of incubation. Malarial parasites are
      strongly inhibited by ethanol concentrations which are attainable by extensive
      alcohol consumption.

PMID- 10890138
TI  - Imported malaria: six cases of severe Plasmodium falciparum infection in
      Innsbruck, Austria, within a period of five weeks (February/March 1999)
AB  - Six patients (age, 30-76; 3 male, 3 female) with severe malaria tropica were
      admitted to the Department of Internal Medicine of the Innsbruck University
      Hospital within a time period of five weeks. All patients had recently visited
      classical malaria regions some days before admission: five patients the sub
      Saharan Africa and one patient Thailand and Vietnam. All six patients had to be
      treated in the Intensive Care Unit. Three patients developed an acute respiratory
      distress syndrome. Two patients died of multi-organ failure. All six patients
      were treated with quinine and doxycycline intravenously. In one case, exchange
      transfusion was performed. Only two of six patients had taken prophylactic
      medication: one patient chloroquine and proguanil and the other mefloquine (she
      suffered from a severe gastroenteritis during the journey).

PMID- 10890139
TI  - [Congenital malaria due to Plasmodium falciparum and Plasmodium malariae].
AB  - Increasing tourism and growing numbers of immigrants from malaria-endemic
      countries are leading to a higher importation rate of rare tropical disorders in
      European countries. We describe, to the best of our knowledge, the first case of
      connatal malaria in Austria. The patient is the first child of a 24 year old
      mother who was born in Ghana and immigrated to Austria one and a half years
      before delivery. She did not stay in an endemic region during this period and did
      not show fever or any other signs of malaria. The boy was healthy for the first
      six weeks of his life. In the 8th week of life he was admitted to our hospital
      due to persistent fever of unknown origin. On physical examination he showed only
      mild splenomegaly. Routine laboratory testing revealed mild hemolytic anemia with
      a hemoglobin value of 8.3 g/l. In the blood smear Plasmodium falciparum and
      Plasmodium malariae were detected. Oral therapy with quinine hydrochloride was
      successful and blood smears became negative for Plasmodia within 6 days. This
      case shows that congenital malaria can occur in children of clinically healthy
      women who were born in malaria-endemic areas even one and a half year after they
      have immigrated to non-endemic regions.

PMID- 10890140
TI  - Cloning genes for non-syndromal hearing impairment.
AB  - Over 45 genes that cause autosomal non-syndromic hearing impairment (NSHI) have
      been localized and many more are predicted to exist. To clone these genes, a
      number of different strategies can be used. This paper focuses on four general
      approaches: functional cloning, positional cloning, position-dependent candidate
      gene cloning, and position-independent candidate gene cloning.

PMID- 10890141
TI  - ENU mutagenesis and the search for deafness genes.
AB  - The availability of mouse mutant models for known human deafness loci is limited.
      Moreover, it is unlikely that the current mouse archives hold mutants for the
      full panoply of genes involved in auditory system development and transduction. A
      large-scale ENU mutagenesis is currently underway to increase significantly the
      number of mouse deafness mutants available, employing specific screens for both
      deafness and balance defects. In the MRC Harwell screen, 13 mice have been
      identified so far with deafness, a balance defect or both. Mutagenized mice from
      the programme are also being used to search for modifiers of a known deafness
      gene, myosin VIIA (mutated in the Shaker 1 mutant mouse). The progress and
      encouraging results of the programme indicate that the combination of ENU
      mutagenesis and effective phenotype screens will lead to a significant
      contribution to the understanding of the genes and mechanisms involved in
      hereditary deafness.

PMID- 10890142
TI  - The DFNA2 locus for hearing impairment: two genes regulating K+ ion recycling in
      the inner ear.
AB  - DFNA2 is a locus for autosomal dominant non-syndromal hearing impairment (ADNSHI)
      located on chromosome 1p34 and six linked families have been identified. An
      audiometric study of these families showed that despite small differences in the
      phenotype all families suffer from progressive hearing impairment starting in the
      high frequencies. A detailed genetic analysis revealed that this deafness locus
      contains more than one gene responsible for hearing impairment. Thus far, two
      genes on chromosome 1p34 have been implicated in ADNSHI. The first, connexin 31
      (GJB3), is a member of the connexin gene family. Connexins form gap junctions.
      These are connections between neighbouring cells that allow transport of small
      molecules. GJB3 mutations were found in two small Chinese families with ADNSHI.
      The second is KCNQ4, a voltage-gated K+ channel. Mutations in KCNQ4 were first
      found in a small French family, later in five of the six linked DFNA2 families.
      No GJB3 or KCNQ4 mutations were detected in patients of an extended Indonesian
      DFNA2 family. Two pathways have been proposed for the recycling of K+ from the
      hair cells back to the endolymph. These pathways involve the use of gap
      junctions, K+ pumps and K+ channels. The expression of GJB3 and KCNQ4 in the
      inner ear and their functions suggest that both DFNA2 genes may play a role in K+
      homeostasis.

PMID- 10890143
TI  - Molecular genetics applied to clinical practice: the Cx26 hearing impairment.
AB  - Mutations in the Cx26/GJB2 gene account for a large proportion of pre-lingual
      hearing impairment with a prevalence up to 50% in autosomal recessive cases and a
      still undefined prevalence in sporadic cases. Ninety-four subjects affected by
      non-syndromal sensorineural hearing impairment (NSHI) were enrolled in the study.
      The patients had either a family history of childhood hearing deficit or
      represented sporadic cases. The risk of an acquired cause of the deficit has been
      carefully excluded. Audiological characteristics were investigated. Cx26
      mutations were found in 50% of subjects. Seventy-three per cent of mutations in
      this gene were 35delG, with significant geographical variations. In 7% of the
      putative Cx26 alleles no mutations were detected either in the coding region or
      in the non-coding exon 1. Cx26 hearing impairment involves all frequencies, is of
      variable severity, and is very rarely progressive and most frequently symmetrical
      between the two ears. The high occurrence of this type of pre-lingual hearing
      impairment argues for modification of the protocols used to investigate the
      aetiology of childhood hearing impairment. Early screening for Cx26 mutations in
      all patients with non-syndromal familial and sporadic permanent childhood hearing
      impairment seems justified.

PMID- 10890144
TI  - The COCH gene: a frequent cause of hearing impairment and vestibular dysfunction?
AB  - The identification of genes leading to hereditary hearing impairment is one of
      the ways to elucidate the functioning of the inner ear. Over the past few years,
      several genes responsible for non-syndromal hereditary hearing impairment have
      been identified. One of these genes, named COCH, is responsible for autosomal
      dominant progressive sensorineural hearing loss associated with vestibular
      impairment (DFNA9). Histopathological analysis in patients with a COCH mutation
      revealed the presence of an acidophylic mucopolysaccharide deposit in the inner
      ear. An overview of the clinical, pathological and genetic studies on COCH is
      given, and the possible role of COCH in the pathology of DFNA9 is discussed.

PMID- 10890146
TI  - Diagnosis and management strategies in congenital atresia of the external
      auditory canal. Study Group on Otological Malformations and Hearing Impairment.
AB  - This consensus report represents a distillation of current opinion regarding
      diagnosis and management of congenital aural atresia. It also takes into account
      the philosophical differences which exist in Europe. Congenital aural atresia
      requires prompt diagnosis, genetic counselling and an early assessment of
      hearing. In bilateral atresia, early amplification with a bone conduction hearing
      aid is essential for proper speech development. Further rehabilitation in
      bilateral cases is managed with surgical reconstruction in selected patients or
      by implantation of a bone-anchored hearing aid. Atresia repair surgery is
      worthwhile if proper patient selection is made by use of stringent audiological
      and radiological criteria and state of the art surgery is performed. The
      divergent views concerning indications, ideal age for surgery and surgical
      approach to achieve better hearing are discussed. Review of the literature
      demonstrated that even in the hands of the best surgeons a mean hearing gain of
      only 20-25 dB is achieved in atresia Type II, with 30-35 dB in Type I. Therefore,
      surgical reconstruction should only be done in the more favourable cases where
      post-operative hearing of <25-30 dB is attainable. Less favoured patients should
      be helped with bone-anchored hearing aids, as this type of surgery does not
      interfere with the future use of new techniques.

PMID- 10890145
TI  - Clinical and radiological evaluation in children with microtia.
AB  - The management of a child with congenital ear malformation, in particular if the
      external ear is severely involved, is difficult because of the complexity of the
      therapeutic problem, and that of parental anxiety. It is very important to plan a
      complete therapeutic/habilitative programme as soon as possible, even if surgical
      procedures are delayed. Diagnostic imaging plays an important role in the global
      assessment of a child with microtia, in order to diagnose possible associated
      external auditory canal, middle and inner ear malformations. For these reasons
      our diagnostic protocol for children with microtia includes otological and
      audiological evaluation, clinical genetics and radiological imaging, from the
      neonatal period. Here, data are reported on 27 children with microtia who
      completed the diagnostic protocol. In eight of 27 cases microtia was bilateral:
      in unilateral cases the right side was affected more frequently. Other congenital
      malformations were diagnosed in 41% of cases. A high correlation between the
      degree of microtia and the frequency of external and middle ear dysplasias was
      found, in accordance with larger studies of the literature. Inner ear
      malformations were found less frequently, but without apparent correlation with
      the degree of microtia. The fact that children with microtia may also have severe
      inner ear malformations is emphasized.

PMID- 10890147
TI  - Audiological findings in patients with microdeletion 22q11 (di
      George/velocardiofacial syndrome).
AB  - Microdeletion 22q11 (del22q11) is one of the most frequent causes of genetic
      syndromes. The majority of cases of di George and velocardiofacial syndromes are
      due to del22q11. These conditions are considered to be developmentally related to
      neural crest anomalies influencing the differentiation of the branchial arches,
      including the percursor tissue of the ear. In addition, the UFDIL gene, an
      ubiquination gene being expressed during embryogenesis in the inner ear
      primordia, has been identified in the 22q11 critical region. The aim of this
      study was to evaluate the prevalence of hearing impairment in del22q11 syndrome.
      Admittance audiometry, behavioural pure tone audiometry and auditory brainstem
      response (ABR) were performed in 27 children studied at our hospital between 1997
      and 1998. Results were related to clinical history, frequency otitis media and
      immune status. Sensorineural hearing loss was found in 4/27 (15%) patients
      (severe in three cases, mild in one), conductive hearing impairment in 12/27
      (45%) (moderate in four cases, mild in eight) and normal hearing in 11/27 (40%).
      Interestingly, three of the patients with sensorineural hearing loss had cerebral
      lesions due to neonatal distress, to hydrocephalus and to post-surgical ischaemia
      each in one. The prevalence of speech delay, otitis media and low CD3 values was
      higher among patients with conductive hearing impairment in comparison with those
      with normal hearing. In conclusion, hearing impairment was documented in 60% of
      the patients and must be included among the clinical features of del22q11
      syndrome. Audiological evaluation is recommended in patients with del22q11 in
      order to reduce the risk of speech deficit.

PMID- 10890148
TI  - Non-syndromal autosomal dominant hearing impairment: ongoing phenotypical
      characterization of genotypes.
AB  - This review is concerned with the present state of phenotypical characterization
      of known genotypes of non-syndromal autosomal dominant hearing impairment. A
      brief outline of history and context of phenotyping and genotyping of hearing
      impairment is given with particular reference to the most recent developments in
      this field, followed by descriptions of DFNA1, DFNA2, DFNA5, DFNA6/14, DFNA8/12,
      DFNA9, DFNA 13, DFNA17 and DFNA21. Phenotyping those known genotypes may support
      the ongoing search for mutations in the corresponding gene and enhance genetic
      counselling. It is recommended that sufficient attention is given to a detailed
      description of the phenotype in each (newly) described hereditary hearing
      impairment disorder.

PMID- 10890149
TI  - BSA recommended procedure.

PMID- 10890150
TI  - Irrigation temperatures.

PMID- 10890151
TI  - Evidence-based audiology.

PMID- 10890152
TI  - sp2-bridged diaryl retinoids: effects of bridge-region substitution on retinoid X
      receptor (RXR) selectivity.
AB  - RXR class selectivity and RXR transcriptional activation activity compared to
      those for the retinoic acid receptor subtypes were enhanced on the 4-(5,6,7,8
      tetrahydro-5,5,8,8-tetramethyl-2-naphthalenylethenyl)be nzoic acid scaffold and
      its 3-methyl analogue by replacing their 1,1-ethenyl bridge by a 1,1-(2
      methylpropenyl) or cyclopropylidenylmethylene group.

PMID- 10890153
TI  - 4-[3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)phenyl]benzoic acid
      and heterocyclic-bridged analogues are novel retinoic acid receptor subtype and
      retinoid X receptor alpha agonists.
AB  - Aromatic retinoids having a meta-substituted aromatic ring bridge, such as 4-[3
      (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)phenyl]benzo ic acid and
      its 3,5-diaryl-substituted 4,5-dihydroisoxazole analogue, function as retinoid
      receptor panagonists by activating both retinoic acid and retinoid X receptors to
      induce gene transcription, and thereby provide novel scaffolds for retinoid drug
      development. Both classes of these ligand-inducible transcription factors are
      involved in mediating the inhibitory effects of retinoids on cancer cell growth.

PMID- 10890154
TI  - Synthetic conversion of ACAT inhibitor to acetylcholinesterase inhibitor.
AB  - Natural product acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor
      pyripyropene A was synthetically converted to acetylcholinesterase (AChE)
      inhibitor via heterolitic cleavage of the 2-pyrone ring, followed by gamma
      acylation/cyclization with several aroyl chlorides. The 4-pyridyl analogue
      selectively showed AChE inhibitory activity (IC50 7.9 microM) and no ACAT
      inhibitory activity IC50 = >1000 microM.

PMID- 10890155
TI  - Synthesis and bioactivities of novel piperidylpyrimidine derivatives: inhibitors
      of tumor necrosis factor-alpha production.
AB  - New piperidylpyrimidine derivatives, including quinazolines, were prepared, and
      their abilities to inhibit TNF-alpha production evaluated. Some compounds showed
      potent inhibitory activity in mouse macrophages stimulated with LPS. The
      synthesis and structure activity relationships of these compounds are described.

PMID- 10890156
TI  - DNA-cleavage studies on N-substituted monocyclic enediynes: enhancement of
      potency by incorporation of intercalating or electron poor aromatic ring and
      subsequent design of a novel phototriggerable acyclic enediyne.
AB  - A number of novel N-substituted enediynes (azaenediynes) 1-4 were synthesized as
      DNA cleaving agents. Enhancement of DNA cleavage potency was observed with those
      compounds which could interact with DNA through intercalation of the extended
      aromatic ring or through electrostatic attraction with electron poor aromatic
      ring. An acyclic enediyne 5 with a novel phototriggerable device was also
      synthesized and its DNA-cleaving activity was established.

PMID- 10890158
TI  - A model for ZnII-containing-beta-lactamase: synthesis, X-ray crystal structure of
      a zinc(II) complex bearing thiol group and hydrolysis of phosphate diester.
AB  - A novel N3S1 typed tripodal ligand bearing an SH group, N-(mercaptoethyl)-di(2
      pyridylmethyl)amine, DPASH, was prepared and its zinc(II) complex,
      [ZnII(DPAS)Cl], was structurally characterized by X-ray crystallography.
      [ZnII(DPAS)Cl] promoted hydrolysis of sodium bis(p
      nitrophenyl)hydrogenphosphate), BNP-.

PMID- 10890157
TI  - Structure-activity relationships study at the 3'-N position of paclitaxel. Part
      2: synthesis and biological evaluation of 3'-N-thiourea- and 3'-N-thiocarbamate
      bearing paclitaxel analogues.
AB  - The syntheses and preliminary biological evaluation of 3'-N-thiocarbamate- and 3'
      N-thiourea-bearing paclitaxel analogues, 4a-f and 5a-e, are described. 3'-N
      thiocarbamates 4a-e were found to be more potent than paclitaxel in both the
      tubulin polymerization assay and the in vitro cytotoxicity assay. Several
      derivatives of this class such as 4c, 4d, and 4e also exhibited some in vivo
      activity.

PMID- 10890159
TI  - Thiosugars. Part 5: synthesis and biological activity of 1-(4-thio-L
      arabinofuranosyl)-5-halopyrimidine nucleosides.
AB  - 1-O-Acetyl-2,3,5-tri-O-benzyl-4-thio-L-arabinofuranoside (6) was transformed in
      two steps into the 1-(4-thio-L-arabinofuranosyl)-5-halopyrimidine nucleosides 10,
      11 and 12, obtained as anomeric mixtures which were separable in the case of 10
      and 11. No in vitro antiviral activity against HIV-1 and HIV-2. TK+ and TK- VZV
      and CMV has been found for 10, 11 and 12.

PMID- 10890160
TI  - Prenylated xanthones as potential P-glycoprotein modulators.
AB  - Dimethylallyl (DMA) derivatives of a naturally occurring xanthone (decussatin 1)
      were prepared. Their activity as potential P-glycoprotein inhibitors was
      monitored by affinity of direct binding and compared to that of corresponding DMA
      flavones. Both classes of compounds exhibited the same structure-activity
      relationships. Decreasing polarity enhanced the binding affinity for the P
      glycoprotein C-terminal cytosolic domain since DMA derivatives were more active,
      but unsubstituted hydroxyl group close to the carbonyl was required for efficient
      activity.

PMID- 10890161
TI  - Synthesis and uptake of nitric oxide-releasing drugs by the P2 nucleoside
      transporter in Trypanosoma equiperdum.
AB  - A series of S-nitrosothiols, structurally related to the NO*-donor S-nitroso-N
      acetylpenicillamine, and of organic nitrate esters that contain amidine groups
      which specify a recognition via the trypanosomal purine transporter P2, were
      synthesized and tested for their ability to inhibit the uptake of [2
      (3)H]adenosine on Trypanosoma equiperdum.

PMID- 10890162
TI  - Nonpeptide endothelin antagonists: from lower affinity pyrazol-5-ols to higher
      affinity pyrazole-5-carboxylic acids.
AB  - Random screening of compounds in endothelin receptor (ET(A) and ET(B)) binding
      assays led to the discovery of a new class of pyrazol-5-ol ligands.
      Characterization of structural features crucial for binding activities of these
      pyrazol-5-ols, by structure activity-relationship (SAR) studies, allowed us to
      design a novel class of pyrazole-5-carboxylic acids as more potent ET
      antagonists.

PMID- 10890163
TI  - Convergent synthesis of ribonuclease L-active 2',5'-oligoadenylate-peptide
      nucleic acids.
AB  - 2-5A was conjugated to N-(2-aminoethyl)-glycyl PNA by periodate oxidization,
      followed by coupling with amino-derivatized PNA and final cyanoborohydride
      reduction. An adduct of 2-5A pentamer with tetrameric thymine PNA activated RNase
      L with the same potency as earlier versions of 2-5A-PNA or 2-5A-DNA.

PMID- 10890164
TI  - Solid-phase synthesis of muramyl dipeptide (MDP) derivatives using a multipin
      method.
AB  - Solid-phase synthetic method of muramyl dipeptide derivatives is reported. A
      diverse library of muramyl dipeptides could be potentially synthesized by
      acylation, reductive alkylation, sulfonamide formation, urea formation, N
      alkylation, amine addition, or component Ugi reactions based on this method for
      drug screening.

PMID- 10890165
TI  - Synthesis of simplified herboxidiene aromatic hybrids.
AB  - The syntheses of simplified aromatic hybrids of the novel polyketide herboxidiene
      (1) are described. One of the hybrids prepared showed significant herbicidal
      activity against broad-leaved weeds in post-emergent application.

PMID- 10890166
TI  - Synthesis and binding to plant lectins of sulfur-containing analogues of
      betaGal1,3 alphaGalNAc (T-antigen).
AB  - Analogues of the tumor-associated T-antigen (betaGal1,3 alphaGalNAc) containing
      4,6-epidithio and 4,6-thietan modifications were synthesized from the alpha-allyl
      glycoside of betaGal alpha1,3GlcNAc via suitable thiocyanate derivatives. Binding
      to three leguminous lectins as model systems was investigated in an enzyme-linked
      lectin assay (ELLA) and IC50 values comparable to the corresponding natural
      disaccharides T-antigen, lactose and N-acetyllactosamine were found.

PMID- 10890167
TI  - Synthesis and cytotoxic activity of acetogenin analogues.
AB  - A set of 16 new simplified analogues of acetogenins has been designed based on:
      (i) the replacement of the bis THF moiety of these natural products by an
      ethylene glycol bis ether unit; (ii) the introduction of different lipophilic
      side chains (alkyl, aryl, dialkylamino, O-cholesteryl); (iii) the presence of the
      same terminal isolactone. In vitro cytotoxic activity against L1210 leukemia is
      reported.

PMID- 10890168
TI  - Synthesis and resolution of racemic eliprodil and evaluation of the enantiomers
      of eliprodil as NMDA receptor antagonists.
AB  - A short synthesis of the NMDA receptor antagonist (rac)-Eliprodil (9) and its
      resolution into the enantiomers by chiral HPLC is described. The enantiomers (R)
      9 and (S)-9 were found to exhibit markedly different affinities for NR2B subunit
      containing NMDA receptors.

PMID- 10890169
TI  - N-(indol-3-ylglyoxylyl)piperidines: high affinity agonists of human GABA-A
      receptors containing the alpha1 subunit.
AB  - A new class of N-(indol-3-ylglyoxylyl)piperidines are high affinity agonists at
      the benzodiazepine binding site of human GABA-A receptor ion-channels, with
      modest selectivity for receptors containing the alpha1 subunit over alpha2 and
      alpha3. All three receptor subtypes discriminate substantially between the two
      enantiomers of the chiral ligand 10.

PMID- 10890170
TI  - Synthesis of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine as
      potential prodrug of L-dopa.
AB  - The synthesis and in vitro chemical and enzymatic stability of L-(+)-3-(3-hydroxy
      4-pivaloyloxybenzyl)-2,5-diketomorpholine (9) as L-Dopa prodrug are described.
      Prodrug 9 possesses a good lipophilicity (log P = 2.153 +/- 0.017), is stable in
      aqueous buffer solutions (pH 1.3 and 7.4), and in 80% rat and human plasma it is
      turned into L-Dopa.

PMID- 10890171
TI  - Synthesis and biological activities of an alpha-methyl and a beta-methyl
      carbapenem and the corresponding unsubstituted compound.
AB  - The carbapenem potassium salts 4, 7 and 8 were prepared. Their rates of beta
      lactam hydrolysis and their biological activities, particularly their beta
      lactamase inhibiting properties, were examined and explained on the basis of
      their different substitution and pyramidality.

PMID- 10890172
TI  - Synthesis and biological properties of new glycosidic cationic lipids for DNA
      delivery.
AB  - Lipidic glycosides with amino alkyl pendent groups were synthesized and evaluated
      for in vitro DNA transfection activity. The first representative of this new
      class of cationic lipids showed good gene delivery and low toxicity to HeLa and
      3T3 cells.

PMID- 10890173
TI  - Synthesis of hybrid distamycin-cysteine labeled with 99mTc: a model for a novel
      class of cancer imaging agents.
AB  - The synthesis of a hybrid constituted by distamycin A and cysteine labeled with
      the gamma-emitting radionuclide 99mTc to afford the conjugate complex 5 is
      reported. This new radiopharmaceutical is of potential interest as tumor imaging
      agent in diagnostic nuclear medicine. The preparation of the hybrid distamycin A
      cysteine 4 has been achieved by coupling deformyldistamycin A and Boc-Dmt-OH.
      Compound 4 was then successfully labeled with 99mTc by reaction with the novel,
      high-electrophilic, metal-containing fragment [99mTc(N)(PP)]2+ (PP = diphosphine
      ligand) yielding the 1:1 complex 5.

PMID- 10890174
TI  - Structure and properties of members of the hGH family: a review.
AB  - This review will summarize the properties of five variant forms of human growth
      hormone: a disulfide dimer, a glycosylated form, 20 kD-hGH, and two peptides made
      up of portions of 22 kD-hGH. The two pituitary peptides (hGH(1-43) and hGH(44
      191)) have, respectively, insulin-potentiating and anti-insulin properties. Both
      have been detected in serum. The shorter peptide may prove to be useful in
      decreasing the amount of exogenous insulin required by diabetics. The larger,
      strongly anti-insulin peptide, may be involved in diabetic retinopathy. We
      believe that this peptide is the long sought after diabetogenic substance of the
      pituitary gland.

PMID- 10890175
TI  - GH and bone--experimental and clinical studies.
AB  - GH increases bone formation both via a direct interaction with GH receptors on
      osteoblasts and via locally produced IGF-I (autocrine/paracrine action). GH
      deficiency results in decreased bone mass in both man and laboratory animals and
      treatment of GHD patients with GH for several months results in increased bone
      mass. GH treatment also increases bone mass and the total mechanical strength of
      bones in rats with normal GH secretion. Because of the short duration of GH
      treatment in man with normal GH secretion, the effect on bone mass is still
      inconclusive. The action of GH on bone metabolism in GHD adults is twofold: It
      stimulates both bone resorption and bone formation. A "Biphasic model" of GH
      action in bone remodeling has recently been proposed [1] (Fig. 2). According to
      this model the net effect of GH first results in a loss of bone mass, followed by
      a net increase in bone mass. The transition point occurs when bone formation
      proceeds at a higher rate than bone resorption. Taking all clinical studies of GH
      treatment of GHD adults into account, it appears that the "transition point"
      occurs after approximately six months and that a net increase in bone mass
      usually is seen after 12-18 months of GH treatment. It should be emphasized that
      the "Biphasic model" of GH action in bone remodeling is proposed based on
      findings in GHD adults, and it remains to be clarified whether or not it is valid
      for subjects with normal GH secretion.

PMID- 10890176
TI  - Serum concentrations of 20K human growth hormone in normal adults and patients
      with various endocrine disorders. Study Group of 20K hGH.
AB  - The 20K hGH isoform is produced by alternative splicing of GH mRNA, and comprises
      approximately 10% of all GH in the pituitary. The physiological role of 20K hGH
      remains to be determined partly because of the lack of a simple and specific
      assay. We have established sensitive enzyme-linked immunoadsorbent assays
      (ELISAs) specific to 20K and 22K hGH. The serum levels of 20K hGH after overnight
      fasting was 118 +/- 178 pg/mL (N=282) in normal women, significantly higher than
      in normal men (64 +/- 170 pg/mL, N=226). However, there was no difference in the
      proportion of 20K hGH to 20K plus 22K hGH between men (6.3 +/- 2.6%, N=176) and
      women (6.3 +/- 2.1%, N = 263). No correlation was detected between the ratio of
      20K hGH and age, body height, body weight or body fat mass in normal subjects.
      The proportion of 20K hGH was significantly (P < 0.001) higher in patients with
      active acromegaly (9.2 +/- 2.2%, N=33) and in patients with anorexia nervosa (9.0
      +/- 1.9, N=8), both of which are characterized by chronic elevation of
      circulating GH levels. The proportion of the 20K hGH in successfully treated
      acromegalic patients did not differ from that in normal subjects, suggesting that
      GH-producing pituitary tumors secrete a higher proportion of 20K hGH, or chronic
      excess of 22K hGH altering the metabolic clearance rate of 20K hGH. The values in
      patients with adult growth hormone deficiency (GHD), hyperthyroidism, primary
      hypothyroidism, or GH-independent short stature did not differ from those in
      normal subjects. The 20K ratio did not change after acute GH provocative tests
      such as insulin tolerance test and GRH test. These results suggest that secretion
      of 20K hGH from the pituitary is under the same control as that of 22K hGH.

PMID- 10890177
TI  - The mechanism of arginine- and insulin-induced GH release in humans.

PMID- 10890178
TI  - Growth hormone increases the CD4/CD8 ratio in splenic lymphocytes in
      glucocorticoid-treated rats.

PMID- 10890179
TI  - Recurrence of sellar and suprasellar tumors in children treated with hGH-
      relation to immunohistochemical study on GH receptor.
AB  - PURPOSE: GH replacement therapy is required in the majority of children with GH
      deficiency after treatment of sellar and suprasellar tumors. Owing to the high
      cell proliferative ability of human GH (hGH), its influence on tumor recurrence
      has been debated. We retrospectively studied the immunohistochemical expression
      of the GH receptor in various tumor tissues, in order to investigate the relation
      between tumor recurrence and hGH replacement. METHODS: GH replacement therapy was
      performed in 25 patients (8 boys and 17 girls) after the treatment. Tumor
      recurrence was noted in 4 patients (craniopharyngioma: 2 patients, pilocytic
      astrocytoma and germinoma: 1 each). Immunohistochemical study of GH receptor in
      tumor tissue was carried out in those recurrent and recurrence-free cases, by
      using MAb 263 as a primary antibody. RESULTS: Two patients with recurrent
      craniopharyngioma were positive for MAb 263, but 1 recurrence-free patient was
      negative. Patients with pilocytic astrocytoma (recurrent and recurrence-free: 1
      each) were all positive. Five patients with germinoma (1 with recurrence and 4
      without recurrence) were all negative. CONCLUSION: In the patients with
      craniopharyngioma treated with GH, a positive immunohistochemical expression of
      GH receptor in tumor tissue may indicate a high probability of recurrence. In our
      cases, GH receptor was positive in astrocytomas and negative in germinomas, with
      or without recurrence. It is therefore speculated that each brain tumor may have
      its specificity in GH receptor expression.

PMID- 10890180
TI  - 20 kDa human growth hormone (20K hGH) stimulates insulin-like growth factor-I
      (IGF-I) gene expression at lower concentrations than 22K hGH in hGH receptor
      expressing Ba/F3 cells.
AB  - Growth hormone (GH) secreted from the pituitary is essential for postnatal growth
      in animals. GH exerts its actions by a direct effect on target organs and by
      stimulating insulin-like growth factor I (IGF-I) production. In the human
      pituitary, there is a naturally occurring variant protein which has a molecular
      mass of 20 kDa (20K hGH) besides the major 22 kDa hGH (22K hGH), but the
      physiological actions of 20K hGH are still poorly understood. In this study we
      have examined its effects on the IGF-I mRNA expression in the pro B-cell line
      Ba/F3 cells stably expressing hGH receptor (Ba/F3-hGHR). Ba/F3-hGHR cells were
      incubated for 2 h with a series of various concentrations (10 pM to approximately
      10 nM) of 20K or 22K hGH. The IGF-I mRNA expression in the Ba/F3-hGHR cells was
      detected by the RT-PCR method. IGF-I gene expression was increased by 20K and 22K
      hGH stimulation, but not by PRL or IL-3 in the Ba/F3-hGHR. And this effect was
      not observed in parental Ba/F3 cells. Lower concentrations of 20K hGH more
      strongly induced IGF-I gene expression than 22K-hGH. These results suggest that
      20K and 22K hGH stimulate the IGF-I gene expression in the Ba/F3-hGHR through hGH
      receptors, and that the stronger effect of 20K hGH than that of 22K hGH in
      enhancing the IGF-I gene expression may be correlated with a 20K hGH specific
      receptor dimerization mechanism.

PMID- 10890181
TI  - Insulin-like growth factor-I (IGF-I)/IGF-I receptor axis and increased invasion
      activity of fibroblasts in keloid.
AB  - Activation of signals for insulin-like growth factor-I receptor (IGF-IR) is
      thought to be closely linked to abnormal cell proliferation and differentiation
      in various diseases. The keloid in which fibroblasts invade beyond the margins of
      the original wound, is a dermal fibroproliferative tissue of unknown etiology.
      Clinically, keloids are most commonly observed in subjects at ages between 10 and
      30 years. Interestingly, plasma levels of growth hormone and IGF-I are also high
      during the same period, suggesting that IGF-I might be involved in the patho
      physiology of keloid fibroblasts. We therefore first examined the expression
      level of IGF-IR in normal and keloid tissues. Immunohistochemical analysis
      confirmed increased expression of IGF-IR in keloid fibroblasts, but not in normal
      fibroblasts. On the other hand, the staining intensity of IGF-IR in the epidermis
      of normal tissues was almost equal to that in keloids. Next, to study the
      functional properties of the IGF-I/IGF-IR axis in both normal and keloid
      fibroblasts, we investigated invasion activities. The invasive activity of IGF-IR
      overexpressing keloid fibroblasts was greatly increased in the presence of IGF-I,
      and inhibited by a neutralizing antibody to IGF-I. In contrast, its activity of
      IGF-IR weak-expressing normal fibroblasts was not changed. Our results indicate
      the involvement of the activated IGF-I/IGF-IR axis in the pathogenesis of the
      invasive activity of fibroblasts.

PMID- 10890182
TI  - Recovery of normal growth in spontaneous dwarf rats (dr) by targeted expression
      of the human GH transgene to the pituitary gland.

PMID- 10890183
TI  - Subcutaneously administered prolactin and 20K hGH, but not rGH or 22K hGH,
      prevent restraint stress-induced gastric ulcers in rats.
AB  - Stress causes gastric ulcer in vertebrates. In humans, growth hormone (hGH) and
      prolactin (hRPL) are promptly released into the circulation under the stress
      conditions, while in rats exposed to stress, the circulating levels of GH (rGH)
      are decreased and the circulating PRL (rPRL) levels are rapidly increased as in
      humans during stress. However, the roles of the circulating rGH and rPRL during
      stress are still unclear. Here we analyzed whether 22K hGH, 20K hGH or rGH, when
      compared to rPRL, can affect restraint stress in water (RSW)-induced gastric
      ulcers. Pretreatments of rats with subcutaneously (s.c.) administered rPRL or 20K
      hGH clearly prevented the development of the gastric injuries in rats subjected
      to 7 h RSW. The s.c. pretreatment with 22K hGH resulted in little cytoprotection
      in the rats exposed to RSW, while s.c. pretreatment with rGH showed no such
      protective effect against RSW-induced gastric injuries. Results suggested that
      rPRL and 20K hGH were acting on PRL receptor, but not on GH receptor, to prevent
      RSW-induced gastric injuries.

PMID- 10890184
TI  - Regulation of pituitary growth hormone-secretagogue and growth hormone-releasing
      hormone receptor RNA expression in young Dwarf rats.
AB  - Growth hormone-secretagogue receptor (GHSR) RNA is known to be expressed in the
      hypothalamus and pituitary. Since endogenous GH secretagogue (GHS) is still
      unknown, the physiological role of GHS and GHSR in growth is not well understood.
      In this study, we have determined the effects of growth hormone in GH-releasing
      hormone receptor (GHRHR) and GHSR RNA expression in spontaneous Dwarf rats (SDRs)
      which are deficient in GH secretion, with or without GH replacement. Twenty-five
      day-old SDRs received daily s.c. injection of human GH (40 microg/kg BW x 2/day)
      or control solution for two weeks. On day 40, the rats were sacrificed by
      decapitation and the pituitaries were immediately removed and quickly frozen.
      Total RNA was extracted from the pituitary, and mRNA coding GHSR was detected and
      semi-quantitated by competitive RT-PCR. Pituitaries from control SDRs showed
      strong GHSR RNA expression and the expression level was 5 to 10 times higher in
      females than in males. When GH was replaced, GHSR RNA expression greatly
      decreased. Pituitary GHRHR RNA expression, determined by RNase Protection Assay,
      was similar in male and female control animals; and was also greatly reduced in
      rats treated with GH when compared to the control. These results suggest that the
      expression of both GHSR and GHRHR is regulated by growth hormone, presumably via
      changes in hypothalamic GHRH and/or endogenous GHS. The apparent sexual
      dimorphism in GHSR indicates different regulatory effects of sex steroid in young
      growing SDRs.

PMID- 10890185
TI  - Incidence of malignant tumors in patients with acromegaly.
AB  - Neoplasms may be one of the systemic complications to which we attribute high
      mortality in acromegaly. The present study was designed to investigate the
      incidence of malignant tumors in patients with acromegaly in the Japanese
      population. In this report, 44 patients (25 men and 19 women) with biochemically
      proven acromegaly were studied retrospectively and had a total 670 patient years
      of the duration of acromegaly. We investigated the incidence of malignant tumors.
      There were 5 patients with malignant tumors (5 in men) in this study (11%). Male
      patients with acromegaly had nearly a 3.5 times higher ratio of malignancy than
      expected and this increased cancer incidence was considered significant (P=0.01).
      There was no significant increase in cancer incidence of either the total patient
      population or female patients. The malignant tumors were two thyroid cancers and
      one colon, one gastric and one bladder cancer. It is of note that the colon
      cancer of one patient was diagnosed 2 years after transsphenoidal surgery even
      though the levels of serum GH and insulin-like growth factor (IGF-1) were reduced
      to normal after operation. This preliminary study has suggested that male
      patients with acromegaly might have a high risk of malignancy and that careful
      screening for tumors is needed both before and after surgical and medical
      treatment, even in patients with normalized serum GH and IGF-1 levels.

PMID- 10890186
TI  - Pre-and post-operative respiratory assessment of acromegalics with sleep apnea-
      bedside oximetric study for transsphenoidal approach.
AB  - PURPOSE: Although routine mechanical nasal packing after transsphenoidal surgery
      (TS) is thought to increase respiratory disorders during sleep, there has been
      little in the literature about the pre- and post-operative airway assessment of
      acromegalics with sleep apnea (SA). We describe 4 acromegalic patients with SA,
      who underwent transsphenoidal surgery. METHODS AND CASES: The patients were all
      men, aged from 47 to 59 years. The pre- and post-operative sleep study consisted
      with a computer calculated oximetry parameter of oxygen desaturation index (ODI),
      which was defined as the number/hour of oxygen desaturation episodes exceeding 4%
      from the base line (normal range < 15). The postoperative (postop.) sleep study
      was carried out from the 1st postop. day to the 8th day, for 1 to 8 days, varying
      for each patient. RESULTS: Only the worst postop. result is shown. Patient 1 had
      2 operations, 2 years apart. ODI was 39.6 before the 1st operation and 45.9
      postop.. In the second operation ODI was 21.8 preoperatively (preop.) and 57.9
      postop.. Preop. and postop. ODI was 18.1 and 22.2 in patient 2, 21.6 and 22.5 in
      patient 3 and 45.5 and 18.9 in patient 4, respectively. ODI of patient 4 was
      39.6, 3 weeks later. CONCLUSION: Our data showed that the postop. oxymetric study
      commonly showed worse results in acromegalics with nasal packing. The better
      result of patient 4 was probably due to a postop. sleepless state. REM sleep
      usually increases in the first several postop. days, when cardiopulmonary
      complications are more likely to occur. Since acromegalics with severe SA and
      postop. nasal packing may more readily suffer from cardiopulmonary complications,
      postoperative meticulous respiratory monitoring and care should be mandatory.

PMID- 10890187
TI  - Bone CT evaluation of nasal cavity of acromegalics--its morphological and
      surgical implication in comparison to non-acromegalics.
AB  - PURPOSE: In order to numerically compare the morphological differences of the
      nasal cavity and nasal sinus between acromegalics and non-acromegalics, bone
      window CT scans sliced parallel to the transsphenoidal surgical route were
      performed. MATERIAL AND CASES: Acromegalic patients had small or large
      macroadenomas and were 13 (7 men and 6 women) in number, aged 53.2 +/- 16.1
      years. Non-acromegalic patients had pituitary tumors and were 44 (21 men and 23
      women) in number, aged 52.1 +/- 12.5 years. RESULTS: The results of acromegalics
      are described in comparison to non-acromegalics in parentheses. a) The width of
      the surgical corridor: piriform aperture, 27.6 +/- 2.7 (25.9 +/- 2.6) mm; origin
      of inferior nasal concha, 29.4 +/- 9.4 (26.6 +/- 4.0) mm; and origin of middle
      nasal concha, 29.8 +/- 3.2 (26.2 +/- 4.2) mm. b) The depth of the surgical
      corridor: the upper lip thickness, 18.1 +/- 2.7 (13.3 +/- 1.4) mm; the distances
      between piriform aperture and sphenoid wall, 52.9 +/- 4.6 (49 +/- 4.2) mm;
      sphenoid wall and sellar floor, 17.3 +/- 4.1 (18.7 +/- 4.1) mm; and sellar floor
      to dorsum sellae, 17.6 +/- 3.4 (15.6 +/- 4.0) mm. c) Marked carotid prominence:
      7/13=53.4% (8/44=18.25%). d) Sinusitis: 8/13=61.5% (12/44=27.3%). DISCUSSION &
      CONCLUSION: The data presented above show that morphological differences in bony
      nasal cavity and soft tissue may be responsible for a deeper and narrower
      surgical field for acromegalics. Acromegalics had a marked carotid prominence
      more frequently, which needs special attention to avoid carotid injury, when
      enlarging the surgical field. Knowing these morphological differences will
      provide useful information for peri- and intra-operative care.

PMID- 10890188
TI  - Glucocorticoid-dependency on GH secretion and tumor growth in a GH-producing
      pituitary adenoma with Cushing's syndrome.
AB  - We report a rare case of a 40-year-old woman with Cushing's syndrome and
      Acromegaly. At the age of 28 she was diagnosed with Cushing's syndrome due to a
      left adrenal tumor concomitant with a GH-producing pituitary tumor. Before
      adrenal surgery her basal GH levels were extremely high and CT scanning revealed
      a high-density mass in the sella turcica. A 28 g left adrenocortical adenoma was
      removed by adrenalectomy. During the four months after the adrenalectomy, basal
      GH levels dramatically decreased and the high-density mass detected by CT
      scanning had disappeared but the basal GH levels and IGF-1 had not been
      normalized. She gradually became acromegalic in the twelve years after the
      adrenalectomy. At the age of 40 CT scanning showed reappearance of the pituitary
      tumor. In order to examine the glucocorticoid dependency on GH secretion, we
      compared the GH secretion in a series of endocrinological tests before and after
      oral 8 mg dexamethasone administration for 7 days. There was no difference
      between before and after dexamethasone administration in the GH secreting
      pattern, but basal GH levels were apparently increased after dexamethasone
      treatment. Transsphenoidal surgery was done and pathological examination showed a
      GH-producing pituitary adenoma. In vitro, dexamethasone increased GH secretion
      from the cultured GH-producing adenoma cells in a dose-dependent manner. In this
      case, both GH secretion and pituitary tumor growth seemed to be dependent on
      glucocorticoid.

PMID- 10890189
TI  - Octreotide improved ventricular arrhythmia in an acromegalic patient.
AB  - We saw a remarkable effect of octreotide, the long-acting somatostatin analogue,
      in reducing the number of ventricular premature complexes (VPCs) in a 59-year-old
      woman with acromegaly. Her basal GH and IGF-1 levels were up to 22.9 ng/ml and
      934.9 ng/ml respectively. MRI revealed a 14 x 12 x 10 mm mass lesion in the
      pituitary gland. She had hypertension and echocardiography showed an increase in
      left ventricular wall thickness. Electric cardiography showed the presence of
      frequent VPCs and 24-h Holter monitoring revealed 24,277 beats of multifocal
      VPCs/24 h. She was treated with 300 microg/day of octreotide for four weeks
      before transsphenoidal surgery. After octreotide treatment, GH and IGF-1 were
      suppressed to 1.8 ng/ml and 145.3 ng/ml respectively, and the tumor size was
      remarkably reduced. Furthermore, the number of VPCs was also dramatically reduced
      to 2062 VPCs/24-h (8.5% of pretreatment) with 24-h Holter monitoring. This case
      shows that VPCs of acromegalic patients can be controlled by suppressing GH and
      IGF-1 with octreotide, and this agent is useful for reducing both tumor size and
      frequency of VPCs prior to surgery.

PMID- 10890190
TI  - Cavernous sinus invasion and tumor proliferative potential of growth hormone
      producing pituitary tumors.
AB  - PURPOSE: Surgical removal of growth hormone-producing pituitary adenomas (GHomas)
      becomes difficult when they invade the cavernous sinus (CS). We investigated the
      relation among tumor proliferative potential, tumor volume and invasion of GHomas
      to CS. MATERIALS & METHODS: 15 patients with GHoma aged 20-59 years were
      enrolled. The volumes of the adenomas were calculated from MR images and the
      extension to CS was classified into 5 grades according to Knosp's grading system.
      The immuno-histochemical staining for anti-Ki-67 monoclonal antibody (MIB-1) was
      performed and the proliferative potential of GHomas was determined as the
      percentage of MIB-1 labeled nuclei (MIB-1 index). The volume, MIB-1 index and pre
      operative growth hormone (GH) level were compared with CS invasion by single and
      multiple regression analyses. RESULTS: With single regression analyses, CS
      invasion was significantly correlated with both the volume (r=0.69, p<0.01) and
      MIB-1 index (r=0.73, p<0.01), but not with the GH level (r=0.42, p=0.12). The
      volume and MIB-1 index showed a weak correlation but it was not significant
      (r=0.52, p=0.06). With multiple regression analysis, CS invasion was well
      explained by the volume and MIB-1 index of GHomas (r=0.82, p<0.01). About 66% of
      CS invasion was explained by these two factors. CONCLUSIONS: In view of these
      results, not only the volume but also the speed of growth are important for
      GHomas to invade CS. GHomas with a high MIB-1 index may, even if they are small,
      more readily invade CS and need closer post-operative hormonal and neuroimaging
      studies.

PMID- 10890191
TI  - Determination of serum 20-kilodalton human GH (20K hGH) levels in healthy adult
      females.

PMID- 10890192
TI  - Functional significance of prop-1 gene expression in pituitary adenomas.
AB  - Prophet of Pit-1 (Prop-1), which is a paired-like homeodomain transcription
      factor, is capable of binding to sites in an early enhancer of the Pit-1 gene and
      regulating its expression. As human Pit-1 is expressed considerably in pituitary
      adenomas, we studied human Prop-1 gene expression in pituitary adenomas. We also
      sequenced the Prop-1 cDNAs in pituitary adenomas. Human Prop-1 transcript was
      detected in all pituitary adenomas examined by RT-PCR analysis. The expression of
      human Prop-1 in pituitary adenomas was confirmed by in situ hybridization in one
      of the GH-producing adenomas. The sequence analysis of human Prop-1 cDNAs in
      these pituitary adenomas revealed that there were no mutations except 5 silent
      nucleic acid substitutions, suggesting that mutations of Prop-1 gene do not
      represent a frequent mechanism of human pituitary tumorigenesis.

PMID- 10890193
TI  - A role of free insulin-like growth factor-I in dawn phenomenon in children and
      adolescents with type 1 diabetes mellitus.
AB  - It has been hypothesized that a decreased amount of the free form of insulin-like
      growth factor-I (fIGF-I) results in morning hyperglycemia in patients with type 1
      diabetes mellitus. In this study, we attempted to clarify the role of fIGF-I in
      relation to total IGF-I (tIGF-I) and its related peptides or proteins in type 1
      diabetes. Forty-seven patients with type 1 diabetes, mean age 13.7 years, were
      evaluated. Blood samples were obtained for the measurement of BG at 0200, 0400
      and 0700, and of insulin, total IGF-I (tIGF-I), fIGF-I, IGFBP-1 and IGFBP-3 at
      0700. The SD scores (SDS) were determined for the levels of tIGF-I, flGF-I, IGFBP
      1 and IGFBP-3 by using Japanese reference data. The morning increase in BG
      (deltaBG(4-7)) correlated significantly with fIGF-I SDS (r=-0.352, p=0.0152) and
      IGFBP-1 SDS (r=0.438, p=0.0021), but did not correlate significantly with the
      fIGF-I level itself or the ratio of fIGF-I to tIGF-I (f/t IGF-I ratio). Hereupon,
      the f/t IGF-I ratio correlated positively with fIGF-I SDS (r=0.541, p=0.0003).
      The mean+/-SD in the f/t IGF-I ratio was 0.94+/-0.43%, and that in fIGF-I SDS was
      -0.50+/-1.32. The level of IGFBP-I SDS correlated negatively with fIGF-I SDS (r=
      0.472, p=0.0008) and insulin (r=-0.365, p=0.0116). We suggest that the morning
      level of fIGF-I SDS, rather than the fIGF-I level itself, may be a useful marker
      of decreased insulin-like bioactivity in the dawn phenomenon in type 1 diabetes
      mellitus.

PMID- 10890194
TI  - Pediatric pituitary adenoma.

PMID- 10890195
TI  - A boy with normal growth in spite of growth hormone deficiency after resection of
      a suprasellar teratoma.
AB  - We reported a boy with panhypopituitarism after removal of a suprasellar teratoma
      and pituitary stalk transection at the age of 3 months. His growth was
      accelerated after 5 years of age without growth hormone (GH) therapy, although he
      had poor height growth until age 4 under treatment with hydrocortisone,
      levothyroxine sodium, and desamino-D-arginine vasopressin (DDAVP). Hyperphagia
      and obesity developed after surgery. Endocrinological examination revealed no GH
      response to glucagon, low serum levels of insulin-like growth factor (IGF)-1 and
      IGF binding protein-3 (IGFBP-3). Serum prolactin was normal, but serum insulin
      was high. Some patients who received an operation for craniopharyngioma were
      reported to achieve normal growth without GH secretion, but the mechanism is
      still unknown. High serum levels of prolactin or insulin can be associated with
      normal IGF in GH deficient patients. This patient had obesity and high serum
      insulin, which may be related to growth without GH secretion.

PMID- 10890196
TI  - Detection of a silent pituitary somatotroph adenoma in a patient with amenorrhea
      and/or galactorrhea: paradoxical response of GH in TRH or GnRH provocation test.

PMID- 10890197
TI  - Acid-labile subunit (ALS) measurements in children.
AB  - Almost all of the serum IGFs are found in a ternary complex composed of IGF,
      IGFBP-3 and acid-labile subunit (ALS). It was reported that ALS levels were age-
      and sex-dependent. In the present study we measured serum ALS levels in 264
      normal children (145 boys and 119 girls) aged from 5 days to 16 years, and 15
      patients with growth hormone deficiency (GHD) aged from 11 months to 13 years.
      Serum ALS levels increased during childhood, and reached peak values in mid to
      late puberty. ALS levels reached their highest levels 2 years earlier in girls
      than in boys. Serum ALS levels were significantly correlated with serum IGF-I
      levels and IGFBP-3 levels. Serum ALS levels were below -2SD in 6 out of 7
      children with complete GHD (CGHD), while serum ALS levels were below -2SD in 1
      out of 8 patients with partial GHD (PGHD). These results indicate that serum ALS
      levels are regulated by GH, and that the measurement of ALS is useful for the
      diagnosis of CGHD in children.

PMID- 10890198
TI  - Bone mineral density in Turner syndrome: relation to GH treatment and estrogen
      treatment.
AB  - The bone mineral density (BMD) of the second metacarpal bone of the left hand was
      measured in 57 patients with Turner syndrome by the digital image processing
      (DIP) method to study the relations between the treatment regimen and their bone
      mineral density. BMD SD score in the patients who had started the GH treatment
      before 10 years old was within +/-2SD of the standard before 14 years, but the
      score decreased to below -2SD after 14 years. In the patients who had started GH
      treatment after 10 years old, BMD score were significantly lower than -2SD,
      although there was tendency to increased. In the patients who had estrogen after
      15 years old, BMD did not increase with GH alone and slowly increased after
      estrogen replacement. In the other two patients who had started sex steroid
      hormone replacement treatment before 15 years old, BMD maintained +/-2SD. In
      patients who received combined GH and LH-RH analog treatment, their BMD score did
      not increase during LH-RH analog treatment. It slowly increased but was still
      below -3SD after stop of LH-RH analog and start of estrogen treatment. In Turner
      syndrome, GH may play a role in maintaining prepubertal BMD levels [4], and
      estrogen plays an important role in pubertal BMD increment. It is recommended
      that estrogen treatment is started before 15 years of age for maintenance of
      normal BMD level.

PMID- 10890199
TI  - Analysis of the FGFR3 gene in Japanese patients with achondroplasia and
      hypochondroplasia.
AB  - It has been reported that mutations in the FGFR3 gene cause autosomal dominant
      forms of dwarfism, achondroplasia (ACH) and hypochondroplasia (HCH). In the
      present study, we analyzed the FGFR3 gene in 26 Japanese patients with ACH and 14
      with HCH. Genomic DNAs of the patients were isolated from whole blood. For the
      ACH patients, a 164-bp fragment of the FGFR3 gene that spans the entire
      transmembrane domain was amplified by polymerase chain reaction (PCR), and the
      PCR products were analyzed by direct sequencing of the PCR products and by
      digestion of the PCR products with restriction enzymes. For the HCH patients, a
      206-bp fragment of the FGFR3 gene which encodes a part of the TK1 domain was
      amplified, and the PCR products were directly sequenced. The heterozygous G380R
      mutations were identified in all of the 26 ACH patients, whereas the heterozygous
      N540K mutations were identified in 8 out of 14 HCH patients. These results were
      consistent with previous reports from abroad.

PMID- 10890200
TI  - A patient of short stature with normal GH secretion, but a low serum IGF-I level.
AB  - We report the case of a 7-year-old patient of short stature who had normal GH
      secretion, but a very low serum IGF-I level. On admittance, his height and weight
      were 102.2 cm (-3.8S.D.) and 15.7 kg (-1.8S.D.), respectively. His bone age was 2
      years and 8 months. The serum GH responses to insulin, glucagon and L-dopa were
      all normal. GH secretion during sleep was also normal, but the serum IGF-I level
      was very low (29 ng/ml). The serum IGF-I level was greatly increased by the
      administration of GH. No mutation was detected in the GH-1 gene. His height
      velocity was noticeably improved by GH treatment.

PMID- 10890201
TI  - Gonadotropin-releasing hormone analog therapy failed to improve predicted final
      height in two children with central precocious puberty and microcephalus.
AB  - Long-acting gonadotropin-releasing hormone (GnRH) analog treatment for central
      precocious puberty (CPP) suppresses excessive bone maturation by inhibiting the
      pituitary-gonadal axis, and usually assures favorable results for growth
      potential. Recently, we encountered two children with CPP and microcephalus in
      whom GnRH analog therapy arrested pubertal development, but could not suppress
      bone age maturation effectively. Eventually, their final height deteriorated
      rather than improved. The reason why these two cases did not respond to GnRH
      analog therapy remains unknown. However, microcephalus and minor cerebral
      anomalies may have some links to deterioration of final height. Our cases suggest
      that careful evaluation will be required especially for CPP with microcephalus
      throughout treatment with GnRH analog.

PMID- 10890202
TI  - Maternal hypothyroidism in autoimmune thyroiditis and the prognosis of infants.
AB  - We evaluated the developmental prognosis of 31 infants born to mothers with
      autoimmune thyroiditis. Four of the babies developed transient neonatal
      hypothyroidism. Their mothers all had low thyroid hormone concentrations during
      pregnancy. Neonatal thyroid function tended to correlate with maternal thyroid
      function at delivery in babies born to mothers with Graves'disease who were
      taking antithyroid drugs. Since severe fetal hypothyroidism sometimes results in
      neurological damage, it is important to maintain normal maternal thyroid function
      during pregnancy.

PMID- 10890203
TI  - Growth and metabolic disturbances in a patient with total parenteral nutrition: a
      case of hypercalciuric hypercalcemia.
AB  - Hypercalciuria is a common side effect during total parenteral nutrition (TPN).
      We report a patient with long-term TPN, who demonstrated hypercalciuria,
      hypercalcemia and growth retardation. The patient is a six-year-old Japanese girl
      with Hirschsprung disease (jejunal agangliosis). Jejunostomy was performed at one
      month old and since then her nutrition has depended mostly on TPN. When she was 3
      years old, continuous TPN was switched to cyclic TPN (on TPN for 11 hrs and off
      TPN for 13 hrs). The urinary calcium level has been elevated (Ca/Cre ratio, 1.0)
      since 3 months of age, whereas serum calcium levels stayed within normal range
      for a while. The serum calcium levels started to elevate to 12 to approximately
      13 mg/dl when she was 3 years and 8 months old. She showed growth retardation
      (height SD score was -4.2SD when she was 5 years and 8 months old) and
      deteriorated renal tubular function with renal glycosuria, elevated beta 2
      microglobulin (beta2-MG) and N-acetyl-beta-D-glucosaminidase. She was referred to
      our division for the investigation and treatment of growth disturbance and Ca
      metabolism. Her bone age was delayed (BA/CA 0.62) and serum IGF-I level was
      decreased but her GH response to provocation test was normal. Bilateral
      nephrocalcinosis was revealed by renal echogram and CT scan. By reducing calcium
      content in TPN solution, the serum and urinary calcium levels could be maintained
      within normal range and her renal function and growth velocity was improved.

PMID- 10890204
TI  - Markers for bone metabolism in a long-lived case of thanatophoric dysplasia.
AB  - We report a male patient with type 1 thanatophoric dysplasia, now eight years
      old, having a mutation in the FGFR3 gene. Radiological examination at birth
      revealed that the ribs and the bones of the extremities were very short and
      vertebral bodies were greatly reduced in height with wide intervertebral spaces.
      The femurs were shaped like French telephone receivers. Because of respiratory
      insufficiency due to the narrow thorax, the patient has been intubated and
      supported by continuous mechanical ventilation since the day after birth. Since 5
      years of age, despite sufficient caloric intake, his body weight never increased
      above 4700 g, body height 49.0 cm, head circumference 46.1 cm, and chest
      circumference 35.8 cm. Acanthosis nigricance and huge bilateral coral-like
      urolithiases has been present. His mental development was severely retarded but
      he was able to make emotional expressions. Although developments in motor
      functions could not be assessed, his neurodevelopmental milestones in social
      relationships and language perception seemed to be at the level of a 10 to 12
      month old. His bone maturation was also severely retarded. All of the assays of
      his serum and urinary bone formation- or resorption-related substances were
      within normal limits for age. Therefore, bone formation as well as bone
      resorption activities seemed normal and not responsible for his growth
      retardation.

PMID- 10890205
TI  - Influence of stocking density, artificial dusk and group size on the perching
      behaviour of broilers.
AB  - 1. Perching behaviour of Ross broiler chickens was studied in order to increase
      the available space at the floor level. Pens (36 m2) were equipped with wooden
      perches mounted 20 and 33 cm above the litter (5 cm perch length per bird). 2.
      The influences of stocking density (22 vs 11 birds/m2, experiment 1) and of a 10
      min artificial dusk (17 birds/m2, experiment 2) were tested in a 2x2 factorial
      design (n=4 by treatment) including control pens without perches. In experiment
      3, perching behaviour between 2 different group sizes (1020 vs 4590 birds, 17
      birds/m2, no replicates) was compared. 3. The percentage of perching birds (PPB)
      was assessed by scan sampling observations during the 20 to 22 h light period (8
      observations per d, 5 d a week, from week 3). In experiment 2, infra-red video
      recording was performed at the time lights were dimmed and during the dark
      period. In experiment 1, carcase lesions were noted. In experiment 2, tibia
      breaking strength of frequently perching birds was compared with controls. Birds
      were weighed before slaughter and food conversion was calculated. 4. PPB
      increased with age and density (P<0.01) and was highest at the 22 birds/m2
      density during week 6 (mean=10.6%, maximum=13.5%). PPB was not influenced by a 10
      min artificial dusk. In experiment 3, PPB was slightly lower during weeks 5 and 6
      in the large group size compared to the small group size (6.8% vs 7.9%
      respectively in week 6). 5. Prevalence of carcase lesions and tibia breaking
      strengths were unrelated to perch usage. Final body-weights were not influenced
      by the presence of perches except at the 22 birds/m2 density where males were
      slightly heavier in the control pens compared with males in pens equipped with
      perches (2096 g vs 2051 g, P=0.015). Food conversion was independent of the
      presence of perches.

PMID- 10890206
TI  - Ultraviolet radiation and laying pullets.
AB  - 1. Responses to ultraviolet (UV) radiation were studied in two trials. In one
      trial, sexually mature pullets, that had been maintained on an 8L:16D regimen
      from 2 d of age, were exposed sequentially, for periods of 9 to 12 d, to a
      further 8 h of very dim visible light (VDV), to 8 h of UV radiation and, finally,
      to an extra 8 h of normal light (conventional 16L:8D). Individual ovipositions
      were recorded during the last 48 h of each treatment. In the second trial,
      sexually mature pullets which had been allowed to 'free-run' for 14 d under
      continuous normal illumination (LL), were given, in addition to the normal light,
      a 12-h period of UV radiation commencing at midday or midnight for a further 15
      d. During the final 48 h oviposition times were recorded and 4 food intakes for
      each 12-h period were determined. 2. In trial 1, mean oviposition time under VDV
      and UV supplementation was not significantly different from that under the 8L:16D
      regimen. Transfer to a 16L:8D regimen altered mean time of oviposition by about 4
      h. In trial 2, eggs continued to be laid almost at random in all groups. 3. Food
      intake was suppressed during the 12-h period of UV supplementation compared with
      that when the birds were not receiving UV. 4. It is concluded that the addition
      of 8 h of UV radiation (at the intensity used in these studies) to 8 h of normal
      light does not cause a phase shift in the timing of the 'open-period' for pre
      ovulatory luteinising hormone release which determines the time of oviposition.
      Furthermore, the insertion of 12-h periods of UV into continuous illumination
      does not entrain egg laying. 5. The suppressing effect of UV on food intake but
      lack of influence on the timing of the ovulatory cycle suggests that UV (at the
      intensity used in this study) acts principally at the retinal level and, as a
      result, stimulates only behavioural responses in laying birds.

PMID- 10890207
TI  - Mixture experiments: a severe test of the ability of a broiler chicken to make
      the right choice.
AB  - 1. A mixture experiment was used to measure the biological performance (weight
      gain and food conversion efficiency) of broilers from 7 to 21 d of age when Fed 1
      of 13 combinations of 3 protein sources. The objective was to determine the
      combination of ingredients that would maximise biological performance. 2. The
      experiment consisted of 2 diet series: in the 1st series, the 3 protein sources
      used were fishmeal, sunflower oilcake meal and soyabean oilcake meal, and in the
      2nd, the soyabean oilcake meal was supplemented with DL-methionine. The
      combinations of 2 and 3-component mixtures that maximised performance in the 2
      series were then compared with the selections made by chickens offered a choice
      of 2 or 3 components separately. 3. In all cases, the choices made by the
      broilers coincided with those mixtures that maximised performance. 4. It is clear
      from this experiment that broiler chickens will attempt to maximise performance
      by choosing the best possible combination of protein sources when given the
      opportunity to do so.

PMID- 10890208
TI  - Skeletal development in the meat-type chicken.
AB  - 1. This study ascertained how bone of modern meat-type chickens develops under
      typical commercial conditions and compares development with that in genetic
      precursor stock. 2. A modern fast-growing selected strain and a slower-growing
      control strain were used. Birds were weighed weekly. A random sample was taken
      from each population at a range of ages up to 39 d. 3. A tibiotarsus from each
      bird was X-rayed and its dimensions and estimated resistance to bending were
      determined. Cortical bone samples were ashed to measure total mineral, calcium
      and phosphorus content. Cortical samples were also taken for porosity assessment.
      4. As expected, the selected strain grew faster and heavier than the control
      strain. Despite this, both strains demonstrated similar periods of rapid bone
      formation (days 4 to 18) and mineralisation (days 4 to 11), and achieved similar
      estimates of resistance to bending. 5. However, cortical bone of the selected
      strain was less well mineralised and more porous than that of the control strain
      and showed a significant increase in the molar Ca:P ratios above the expected
      range of values during the first 2 to 3 weeks of life. 6. Despite production of
      bones with the correct dimensions for load support, the relatively poor density
      and mineral content of bone in the selected strain is likely to reduce effective
      breaking strength of the tibiotarsus. Possible reasons may be either inadequate
      dietary supply of Ca and P or impaired utilisation of the minerals due to a rapid
      growth rate or genetic factors.

PMID- 10890209
TI  - Long-term egg production and heterosis in quail lines after within-line or
      reciprocal recurrent selection for high early egg production.
AB  - 1. Four Japanese quail lines were developed using 13 generations of reciprocal
      recurrent (lines AA and BB) or within-line selection (lines DD and EE) for high
      egg number until 98 d of age. In these lines and their reciprocal crosses, egg
      production, egg weight and mortality were monitored for up to 21 months to
      evaluate the impact of selection method and line origin on long-term production
      and heterosis. 2. Both hen-housed total egg number (EN) and hen-day egg laying
      rate (ELR) were consistently lower in recurrent lines than in lines under within
      line selection: after 13 months of test, the difference was -47.1 eggs for EN and
      -20% for ELR%, whereas mortality was similar at around 20%. 3. Line EE was the
      best pure line for early egg production (55.2 eggs at 98 d of age) and also gave
      eggs which were consistently about 2 g larger than those from line DD but it had
      the highest overall mortality (78.5%) of all lines. On average, line DD laid 399
      eggs (EN) over the whole experiment, 84 more than Line EE. 4. Crossbreds from the
      2 types of pure lines and line DD had similar patterns and rates of egg
      production during the whole experiment, as indicated by the similarity of the
      curves adjusted for those lines by using the monomolecular model for EN and the
      modified compartmental model for ELR. 5. However, heterosis was higher from
      recurrent selection lines and it increased more with time than did heterosis from
      within-line selection lines.

PMID- 10890210
TI  - Microbial cross-contamination during air chilling of poultry.
AB  - 1. Cross-contamination during air chilling of poultry carcases was investigated
      using a nalidixic acid-resistant strain of Escherichia coli K12 as a marker
      organism. 2. Experiments were carried out on 2 types of commercial chiller, with
      and without the use of water sprays (evaporative cooling), and a pilot-scale
      chiller in which conditions could be varied as required. 3. In the commercial
      chillers, the marker was dispersed in all directions from a single inoculated
      carcase and transmission was increased by the use of chlorinated water sprays. 4.
      Similar results were obtained with the pilot-scale chiller, where the marker was
      recovered from 45/54 uninoculated carcases; cross-contamination was not prevented
      by spraying carcases with water containing 50 mg/l of free available chlorine. 5.
      Despite the ease of microbial transmission from inoculated carcases, cross
      contamination during air chilling is likely to be less than that occurring at
      earlier stages of poultry processing, when carcases are more heavily
      contaminated.

PMID- 10890211
TI  - Effect of dietary iron and copper on performance and oxidative stability in
      broiler leg meat.
AB  - 1. An experiment was carried out to determine the effect of removal of
      supplemental iron and copper from broiler diets during the last 3 weeks before
      slaughter on broiler performance, tissue vitamin E concentrations and oxidation
      values in raw; cooked and stored broiler leg meat. 2. Removal of supplemental
      iron and copper from the diet slightly decreased food efficiency; the differences
      were significant only when both minerals were removed simultaneously 3. Effect of
      iron withdrawal on iron concentration in tissue was low. However, total copper
      concentration in tissue was reduced in animals deprived of iron or both minerals
      simultaneously. 4. Removal of dietary iron and copper did not affect vitamin E
      concentration in raw and cooked meat, while stored meat showed lower
      concentrations in animals deprived of iron and copper simultaneously. 5. The
      removal of iron and copper from the diet reduced oxidation values in cooked
      broiler leg meat as measured by the thiobarbituric acid-reacting substances
      method (TBARS).

PMID- 10890212
TI  - The effect of changing the excreta moisture of caged laying hens on the excreta
      and microbial contamination of their egg shells.
AB  - 1. An experiment that included 1440 caged laying hens in 24 experimental units
      was conducted to determine the effect of differences in excreta moisture on the
      proportion of dirty eggs and the microbial contamination of eggs that were
      ostensibly uncontaminated by excreta. Excreta moisture contents were changed by
      giving the hens diets that contained 4 different concentrations of sodium. 2.
      Diets containing 1.6, 5, 10 or 15 g/kg dietary sodium were fed ad libitum to 1140
      laying hens for a 12-week feeding period. A sample of excreta was collected from
      each experimental unit each week and its moisture content determined. All eggs
      produced were classified as clean or dirty according to the European Community
      Egg Marketing Regulations. A sample of eggs were collected from each experimental
      unit on 4 separate occasions in the last 4 weeks of the feeding period and the
      total bacterial numbers on ostensibly clean egg shells were determined. 3.
      Increasing dietary sodium concentration gave linear (P<0.01) increases in excreta
      moisture. Each 100 g/kg increase in excreta moisture increased (P<0.001) dirty
      egg numbers by 0.52% of the total eggs produced. Increasing excreta moisture gave
      a linear increase (P<0.001) in the (log-transformed) numbers of microorganisms
      that contaminated ostensibly clean egg shells.

PMID- 10890213
TI  - Food safety implication: certain antibiotics may rapidly contaminate egg albumen
      during the process of its formation.
AB  - 1. Egg white formation occurs in 3 phases: synthesis and storage of albumen
      proteins prior to ovulation, secretion of proteins during passage of the ovum
      down the reproductive tract (preplumping) and addition of water (plumping phase).
      2. This study was to determine if oxytetracycline would transfer into egg albumen
      during the latter 2 phases of albumen formation. 3. In 2 experiments 48 hens were
      injected with either 400 mg/kg oxytetracycline or physiological saline. Hens were
      dosed at 0.5 h (preplumping phase) or 5.5 h (plumping phase) after oviposition.
      4. Five hours following injections, hens were euthanised and albumen was
      collected from the reproductive tract. 5. Oxytetracycline transferred into
      albumen during both phases of albumen formation. Concentrations (ppm) were
      greater in the preplump vs plump phase (3.2 vs 1.8 in experiment 1; or 2.8 vs 1.6
      in experiment 2. However, when differences in albumen weights were accounted for,
      total microg transfer did not differ between the 2 phases. 6. Drugs may transfer
      into egg whites during the latter phases of formation prior to oviposition.
      Therefore, poultry producers or veterinary practitioners dosing laying hens must
      consider that egg whites contained in the 1st egg laid after dosing may contain
      drug residues.

PMID- 10890214
TI  - Methods to improve the hatchability of checked chicken eggs.
AB  - 1. The hatchability of checked Leghorn and broiler parent hatching eggs was
      significantly improved by shell treatment: smearing with synthetic adhesive resin
      (Fevicol), or pasting cellophane tape or insulation tape over the checked portion
      of the shell. 2. Shell damage reduced hatchability by increasing evaporative
      loss, leading to embryonic dehydration. 3. Relative chick weight, expressed as a
      percentage of egg weight was lower in untreated checked eggs but comparable
      between intact and shell-treated hatching eggs. 4. The cost of chick production
      can be reduced by shell treatment of checked hatching eggs, especially in broiler
      parent eggs.

PMID- 10890215
TI  - Nutritional evaluation of sunflower seed and products derived from them. Effect
      of oil extraction.
AB  - 1. Apparent MEn and oil digestibility of hulled sunflower seed (SFS) and the
      products derived from the oil extraction process: press extracted SFS (PESFS),
      sunflower seed meal (SFSM), and press and solvent oils (PO and SO) were
      determined with 198 cockerels. Recombined products (mix of meal and oil) were
      also evaluated to study the effect of the 2 consecutive oil extraction steps.
      Each foodstuff was included in a basal diet, according to the proportions
      resulting from processing, at 100, 200, and 300 g SFS/kg. 2. Dietary energy value
      and digestible fat content were linearly related to rate of inclusion of test
      ingredients. Extrapolation values for AMEn (MJ/kg DM) were: SFS, 16.20; PESFS,
      9.46; SFSM, 7.62. A decreasing quadratic trend was also found in the AMEn of
      PESFS, with interpolation values ranging from 11.77 to 9.33 MJ/kg DM between 70
      and 210 g/kg DM of inclusion. No differences were observed between PO and SO. The
      AMEn of of sunflower oil, calculated from its digestibility, was 33.70 MJ/kg DM.
      3. The oil extraction process affected the nutritional value of sunflower
      products. Recombined materials showed greater values than original foodstuffs: R
      SFS, 17.47; R-PESFS, 11.49 MJ/kg DM. The increase in oil digestibility (from
      0.814 to 0.862 g/kg DM in SFS; from 0.778 to 0.892 in PESFS) accounted for most
      of the increase observed in AMEn values. 4. As the form in which oil is
      incorporated in diets (released or within SFS or PESFS) affects the utilisation
      of sunflower products, their nutritional value is less than maximal and should
      not be calculated from their ingredients. Solvent oil seems to be the less
      available fraction of sunflower oil within SFS as the effect of the 2nd
      extraction proved to be greater than that of the previous press extraction.

PMID- 10890216
TI  - Response of broiler chickens to microbial phytase supplementation as influenced
      by dietary phytic acid and non-phytate phosphorous levels. II. Effects on
      apparent metabolisable energy, nutrient digestibility and nutrient retention.
AB  - 1. Male broilers (n=900) were fed on wheat-sorghum-soyabean meal based diets
      containing 3 concentrations of phytic acid (10.4, 13.2 and 15.7 g/kg; equivalent
      to 2.9, 3.7 and 4.4 g/kg phytate P), 2 concentrations of non-phytate (or
      available) phosphorus (2.3 and 4.5 g/kg) and 3 concentrations of microbial
      phytase (0, 400 and 800 FTU/kg) from day 7 to 25 post-hatch. The dietary
      concentrations of phytic acid were manipulated by the inclusion of rice pollards.
      All diets contained celite (20 g/kg) as a source of acid-insoluble ash. 2. The
      apparent metabolisable energy (AME) concentrations of the diets were determined
      using a classical total collection procedure during the 3rd week of the trial. On
      d 25, digesta from the terminal ileum were collected and analysed for phosphorus,
      nitrogen and amino acids. Nutrient digestibilities were calculated using acid
      insoluble ash as the indigestible marker. 2. Ileal digestibilities of nitrogen
      and essential amino acids were negatively influenced by increasing dietary levels
      of phytic acid but these negative effects were overcome by the addition of
      phytase. 3. Supplemental phytase increased AME, ileal digestibilities of
      phosphorus, nitrogen and amino acids and the retention of dry matter, phosphorus
      and nitrogen in broilers. There were no differences in the phytase responses
      between additions of 400 and 800 FTU/kg. 4. The responses in all variables,
      except AME, were greater in low non-phytate phosphorus diets. 5. In the case of
      AME, the response to added phytase was greater in adequate non-phytate phosphorus
      diets. Supplemental phytase increased AME values from 13.36 to 13.54 MJ/kg dry
      matter in low non-phytate phosphorus diets and from 12.66 to 13.38 MJ/kg dry
      matter in adequate non-phytate phosphorus diets.

PMID- 10890217
TI  - The true metabolisable energy content of canola oilcake meal and full-fat canola
      seed for ostriches (Struthio camelus).
AB  - 1. The true metabolisable energy (TME) of canola oilcake and full-fat canola seed
      was determined for ostriches to broaden our knowledge of canola as a potential
      protein and energy source for ostriches. 2. Both test materials were diluted with
      a basal diet, fed to ostriches and TME-values estimated by multiple regression
      analysis. 3. The TME values for canola oilcake meal and full-fat canola seed for
      ostriches were respectively 13.76 MJ kg(-1) and 22.5 MJ kg(-1). 4. The TME values
      obtained for these 2 important protein sources will assist in the more accurate
      formulation of diets for ostriches.

PMID- 10890218
TI  - Protein and body weight accretion of chicks on diets with widely varying contents
      of soyabean meal supplemented or unsupplemented with its limiting amino acids.
AB  - 1. Two studies were conducted to evaluate the effects of relative deficiencies of
      methionine and threonine on the growth performance of 8- to 21-d-old chicks fed
      on isoenergetic diets containing a wide range of crude protein (CP)
      concentrations from dehulled soyabean meal (SBM). 2. Chicks fed on graded levels
      of SBM containing supplemental methionine and threonine (BAL) accreted whole-body
      protein more efficiently (P < 0.05) than those receiving graded levels of
      unsupplemented SBM (DEF), and superior (P < 0.05) growth performance was also
      obtained at lower CP levels when chicks were fed on the BAL diets. 3. Voluntary
      food intake increased between 30 and 220 g CP/kg in chicks fed on DEF diets,
      whereas food intake of chicks fed on BAL diets increased only between 30 and 100
      g CP/kg, after which it decreased between 100 and 220 g CP/kg. 4. Protein
      efficiency ratio (g gain per g protein intake) decreased with each incremental
      increase in CP between 30 and 260 g CP/kg, regardless of whether diets were BAL
      or DEE 5. These data indicate that maintaining a balanced ratio of amino acids is
      a preferable approach when poultry producers are interested in employing low CP
      diets for economic, physiological or environmental reasons.

PMID- 10890219
TI  - The effects of dietary protein independent of essential amino acids on growth and
      body composition in genetically lean and fat chickens.
AB  - 1. Growth performance between 28 and 49 d of age and carcase composition at 49 d
      in genetically lean (LL) and fat (FL) broilers fed on diets varying in non
      essential amino acid (NEAA) concentrations were compared in 2 experiments. In
      experiment 1, 3 crude protein (CP) contents (133, 155, and 178 g/kg) were
      compared. In experiment 2, 4 CP levels (131, 150, 170 and 189 g/kg) were
      compared. All diets were supplemented with synthetic amino acids to cover the EAA
      requirement of the LL birds. 2. Weight gains of FL chickens were not affected by
      dietary treatments, while those of LL increased when CP level increased. 3.
      Reducing CP content always increased body lipids, abdominal fat and food
      conversion ratio in both lines in both experiments; however, the effect on
      abdominal fat was more pronounced in the FL birds. 4. Reducing CP concentration
      always decreased breast muscle proportion in both lines in both experiments, even
      when growth rate was not affected by CP. 5. It is concluded that LL chickens
      require diets more concentrated in NEAA than fat chickens and that there seems to
      be an effect of NEAA on breast muscle development.

PMID- 10890220
TI  - Influence of the method of calcium provision on Marek's disease losses in
      compound and choice fed layers.
AB  - 1. Two strains of layers were fed compound or choice forms of a standard diet and
      given calcium as either ground limestone or coarse limestone grit daily or every
      2nd day. Mortality caused by Marek's disease was monitored during the rearing and
      laying phases. 2. A dramatic difference in Marek's disease mortality was found
      between the strains. Heavy Marek's disease mortality in the imported strain A in
      the rearing phase was not markedly affected by dietary or calcium treatment. 3.
      Method of feeding and calcium provision interacted to influence significantly the
      risk of death due to Marek's disease in the laying phase in layer strain A. 4.
      Choice feeding may adversely influence Marek's disease losses in layers.

PMID- 10890221
TI  - Different responses of protein synthesis to refeeding in various muscles of
      fasted chicks.
AB  - 1. The change in the rate of protein synthesis of different muscles,
      concentrations of plasma insulin, plasma insulin-like growth factor-I (IGF-I) and
      other plasma components were investigated after refeeding in fasted chicks. 5.2 g
      of the complete diet was refed. This was the maximum that could be force-fed with
      water. 2. The fractional synthesis rates (FSR) of breast (M. pectoralis major)
      and leg (M. gastrocnemius) muscles were measured after injection of L-[2, 6
      (3)H]phenylalanine. Plasma insulin and IGF-I concentration were determined by
      radioimmunoassay. 3. In the breast muscle, FSR was significantly reduced by 2-d
      fasting. The FSR had recovered completely after 1 h of refeeding and was
      maintained until 6 h. The change in FSR after refeeding was associated with the
      change in ribosomal efficiency (K(RNA); absolute synthesis rate per unit RNA),
      while no change in ribosomal capacity (C(S); RNA: protein ratio) was observed. 4.
      In the leg muscle, FSR was decreased by 2-d fasting and increased gradually
      toward 6 h after refeeding but did not reach the level of the fed control. In
      contrast to the breast muscle, no significant changes in Cs and K(RNA) in the leg
      muscle were observed. 5. Plasma glucose concentration increased significantly at
      1 h after refeeding but returned to the fasted level after 24 h. Plasma insulin
      concentration in chicks refed for 1 h was higher than in the fasted group. There
      was no significant change in plasma IGF-I concentration. 6. These results suggest
      that the FSR of breast muscle was more sensitive to refeeding than that of leg
      muscle which may be explained, in part, by differences in sensitivity to the
      change in circulating plasma insulin concentration after refeeding.

PMID- 10890222
TI  - Ovarian follicular dynamics in selected and control (relaxed selection) male- and
      female-lines of broiler breeders fed ad libitum or on restricted allocations of
      food.
AB  - 1. The reproductive structures of 4 broiler breeder lines fed ad libitum or
      restricted were compared at 1st egg. The lines were contemporary male- and female
      lines and their respective progenitor lines maintained without selection for 20
      years. 2. The selected lines were larger and had more hierarchical yellow
      follicles than the relaxed lines. The numbers of positions in the hierarchy were
      greater in the selected lines. The number of atretic follicles and the proportion
      of multiple follicles were relatively high in the selected male-line. 3. There
      were more white follicles in the range 1.8 to 5.0 mm diameter in the selected
      male-line than in the relaxed line, whereas selection did not change white
      follicle numbers in the female-line. 4. Food restriction decreased the numbers of
      normal and atretic yellow follicles and the proportion of multiples but had no
      effect on the number of positions in the hierarchy. Restricted feeding decreased
      the number of white follicles 1.4 to 2.4 mm and increased follicles 2.4 to 5.0 mm
      diameter. 5. There was little change in age at 1st egg among lines fed ad
      libitum. Restricted feeding increased age at 1st egg and the difference was
      greater in female- than in male-lines and in relaxed compared with selected
      birds. 6. Abdominal fatness was similar among the lines fed ad libitum and was
      decreased by restricted feeding. 7. Oviduct weights were greater in selected than
      in relaxed lines and were decreased by restricted feeding only in the selected
      male-line. 8. The weight of the largest follicle was higher in the selected lines
      and in restricted compared with ad libitum-fed birds. Plasma triglyceride
      concentrations were lower in restricted birds from the selected and relaxed
      female-lines compared with the other groups. Differences in plasma oestrogen
      concentrations could not be detected.

PMID- 10890223
TI  - Effect of selenium and vitamin E content of the maternal diet on the antioxidant
      system of the yolk and the developing chick.
AB  - 1. The effects of selenium and vitamin E supplementation of the maternal diet on
      their transfer to the egg yolk and tissues of the newly hatched chick and on the
      development of the antioxidant system in the chick liver in early postnatal life
      were investigated. 2. One hundred Cobb broiler breeder hens were divided into 10
      equal groups and housed in pens at 25 weeks of age. Each hen received 1 of the
      treatment diets which included 0.2 or 0.4 mg/kg selenium, 40, 100, 200 mg/kg
      vitamin E or their combination. After 6 weeks, the hens were artificially
      inseminated once per week. From week 8, eggs were collected and placed in an
      incubator. After hatching, chicks from each group were reared (under standard
      commercial conditions) to 10 d of age. The chicks were fed on a standard starter
      commercial broiler diet. At the time of hatching, and at 5 and 10 days old, 4
      chicks from each group were sacrificed and blood, liver and brain were collected
      for the subsequent biochemical analyses. 3. The inclusion of organic selenium or
      vitamin E in the commercial diet significantly increased their concentration in
      the egg and in the liver of 1-d-old chicks obtained from the eggs enriched with
      these substances. A positive effect of such dietary supplementation was seen at d
      5 and d 10 of postnatal development. 4. There was a positive effect of selenium
      supplementation of the maternal diet on glutathione concentration in the liver of
      1-d-old and 5-d-old chicks. A combination of a dietary selenium supplementation
      with high vitamin E doses further increased glutathione concentration in the
      liver. Dietary selenium supplementation significantly increased selenium
      dependent glutathione peroxidase (Se-GSH-Px) activity in the liver of the 1-d-old
      and 5-d-old chicks and decreased liver susceptibility to peroxidation. 6. It is
      concluded that the nutritional status of the laying hen determines the efficiency
      of the antioxidant system throughout embryonic and early postnatal development of
      the offspring.

PMID- 10890224
TI  - Carbonic anhydrase in the utero-vaginal junction of immature and mature
      ostriches.
AB  - 1. Sperm storage tubules in the ostrich start to develop at an early stage of
      oviductal growth. Concurrently, membrane-bound carbonic anhydrase was found in
      the cells of the storage tubules. 2. In mature ostriches the utero-vaginal
      junction averaged 11.5+/-2.1 cm in length and primary mucosal folds were
      extremely long and slender. Membrane-bound carbonic anhydrase was present in the
      cells of the sperm storage tubules. In the non-ciliated cells of the surface
      epithelium both membrane-bound and cytoplasmic activity was detected. 3. The
      possible role of carbonic anhydrase in the stimulation/inhibition of sperm
      motility by altering the pH was discussed.

PMID- 10890225
TI  - Development of a consensus-assisted protocol--a new approach to improve study
      design.

PMID- 10890226
TI  - Mediastinitis after cardiac surgery--epidemiology and current treatment.
AB  - Mediastinal infection is a feared complication observed after 0.4%-5% of cardiac
      operations. Even today the mortality remains as high as 20%-40%. We discuss the
      aetiology, mechanisms, prevention, diagnosis, and medical management. The staging
      system for mediastinal wound infections developed at a joint conference of German
      cardiac surgical centres is presented. The use of parenteral polyvalent
      immunoglobulins is also discussed.

PMID- 10890227
TI  - Efficacy and potential clinical applications of Pentaglobin, an IgM-enriched
      immunoglobulin concentrate suitable for intravenous infusion.
AB  - OBJECTIVE: Characterisation of the antibodies against important human pathogens
      in two immunoglobulin preparations: Intraglobin F and IgM-enriched Pentaglobin.
      DESIGN: In vitro assay of antibody titre using bacterial outer-membrane proteins,
      lipopolysaccharides (LPS), and exotoxins of clinically relevant bacteria.
      METHODS: Antibody reactivities measured by ELISA and immunoblot techniques
      against antigens from bacteria that cause sepsis, antibiotic-resistant nosocomial
      pathogens, and enteric pathogens. RESULTS: IgG anti-LPS reactivity was present in
      both study drugs. Specific IgM antibodies against LPS of gram-negative bacteria
      that cause sepsis were also detected in the IgM-enriched Pentaglobin. IgG
      reactivity against gram-positive multiresistant strains of Staphylococcus aureus
      (S. aureus) were detectable in both preparations. IgG and IgM antibodies present
      against Yersinia outer proteins and Campylobacter jejuni (C. jejuni) outer
      membrane proteins were detected in Pentaglobin. Both preparations reacted against
      alpha toxin of S. aureus and streptolysin of Streptococcus pyogenes. Pentaglobin
      showed a strong IgM-reactivity against alpha-haemolysin. CONCLUSION: Our data
      suggest that infusion of well characterised immunoglobulin preparations might be
      beneficial for patients with severe infections. This is highly relevant in view
      of the high pathogenicity of bacteria that cause infections in patients in
      hospital and the continually increasing antibiotic resistance (particularly
      methicillin-resistant S. aureus).

PMID- 10890228
TI  - A multicentre randomised placebo-controlled double-blind study on adjuvant
      treatment of mediastinitis with immunoglobulins (Pentaglobin) after cardiac
      surgery (ATMI): outline and preliminary study protocol for discussion. The ATMI
      Study Group.
AB  - We present the second draft of a consensus-assisted protocol on the adjuvant
      treatment after cardiac surgery with immunoglobulins of mediastinitis. CLINICAL
      PHASE: Phase III. OBJECTIVE OF THE STUDY: Placebo-controlled investigation of the
      clinical efficacy of Pentaglobin (Biotest, Germany) as an added treatment in
      patients with mediastinitis. MEDICATION: Group A, active Pentaglobin; Group B,
      placebo: 5% glucose solution with 1% human albumin. DOSAGE: 5 ml/kg body weight
      Pentaglobulin or placebo intravenously each day for 5 days. STUDY DESIGN:
      Prospective, placebo-controlled, double blind, randomised, multicentre. SAMPLE
      SIZE: n = 100; 50 patients with Pentaglobin (active), 50 patients with placebo.
      PRIMARY OUTCOME MEASURE: Cumulative therapeutic intervention scoring system (TISS
      28) during hospital stay.

PMID- 10890229
TI  - The overall concept: immunoglobulins as adjuvants for mediastinitis--does it make
      sense?
AB  - Supportive intravenous immunoglobulin (ivIg) treatment may reduce the incidence
      and severity of infections in a well-defined group of patients in intensive care,
      including those who have had cardiac surgery. Sternal wound infections and
      mediastinitis after cardiac surgery are to be investigated in the ATMI study with
      Pentaglobin. In this article I focus on optimising ivIg dosage, on likely
      mechanisms, on reasons why ivIg might improve a primarily gram-positive
      infection, and on the use of serial scoring as an endpoint in a trial of
      immunoglobulin.

PMID- 10890230
TI  - Comments on the study protocol: adjuvant treatment of mediastinitis with
      immunoglobulins (Pentaglobin) after cardiac surgery (ATMI).

PMID- 10890231
TI  - Microbiology and antibiotic treatment--discussion forum on a study protocol on
      adjuvant treatment of mediastinitis with immunoglobulins (Pentaglobin) after
      cardiac surgery (ATMI).

PMID- 10890232
TI  - Thoracic transposition of the greater omentum as an adjunct in the treatment of
      mediastinitis--pros and cons within the context of a randomised study.
AB  - Mediastinitis after cardiac surgery is a rare but life-threatening complication.
      The omentum is particularly well-suited for the treatment of severe sternal wound
      infections, because it contains large numbers of immunologically active cells
      that seem to be responsible for the high anti-infective activity of the omentum.
      The additional transposition of parts of the greater omentum into the thorax was
      discussed in the development of a protocol for the planned ATMI study, which will
      investigate the effectiveness of immunoglobulins in the treatment of severe
      sternal wound infections that require reoperation. We present two different
      points of view about whether omentopexy should be allowed within the study
      design.

PMID- 10890233
TI  - Outcome assessment--the pros and cons of TISS as the primary objective.

PMID- 10890234
TI  - Outcome assessment--TISS as a tool to evaluate cost-effectiveness of
      immunological treatment.
AB  - Nursing costs more than any other element of intensive care. Nurses are allocated
      exclusively to the ICU, and their use can therefore be accurately monitored. The
      amount of nursing work in the ICU is intimately associated with the severity of
      illness of the patients. Consequently, the density of nursing staff in the ICU
      can be used as a measure of cost, and the Therapeutic Intervention Scoring System
      (TISS) is a reliable tool for measuring their workload. TISS is therefore often
      used to compare the costs of alternative courses of care; it covers direct costs
      of care, but it should not be used as a proxy for total costs in the ICU. The
      users of TISS should consider the limitations of the scoring system in some
      aspects of its development, as well as the general nature of the definitions of
      the items included. The careful enunciation of the more generally defined items
      has therefore to be considered when it is used in a research project that
      compares small samples.

PMID- 10890235
TI  - Biostatistical aspects of outcome evaluation using TISS-28.
AB  - Quantification of therapeutic activities using the Therapeutic Intervention
      Scoring System (TISS) is an alternative approach to evaluate outcome of patients
      in intensive care. The reason for using cumulative TISS points is to integrate
      various adverse events (except mortality) according to the amount of therapeutic
      effort that they require. The reduced version of TISS with 28 items (TISS-28)
      allows a reliable assessment of therapeutic activities with limited observer
      variation, provided that an exact description of all items is given. Measurements
      can be validated by correlations with established severity of -disease
      classification systems such as APACHE II. Cumulative TISS-28 values correlate
      well with length of ICU stay (r = 0.98). On average, 27.2 points/day can be
      expected in an unselected mixed surgical ICU. Those who die can be included in
      non-parametric analyses of cumulative TISS values by allocation of arbitrary high
      values. Quantification of therapeutic interventions is a sensitive measure of
      outcome in patients who require intensive care but have a low risk of mortality.
      The usefulness of economic analysis further supports its clinical application.

PMID- 10890237
TI  - Considerations on the statistical design of the ATMI study.
AB  - The ATMI study of prevention of mediastinitis after cardiac surgery uses the
      total amount of therapeutic interventions measured by the TISS-28 score as the
      primary endpoint. The study is designed as an adaptive group-sequential plan with
      three sequences, as experiences with the TISS-28 in cardiac intensive care units
      are scarce. According to the Bauer-Kohne method the sample sizes of the second
      and third sequences can be calculated in a data-driven manner after the results
      of the previous interim analyses are available. Thus the first trial phase can be
      considered as an internal pilot study.

PMID- 10890236
TI  - Organ dysfunction as an outcome measure in clinical trials.
AB  - Serious infection is responsible for both morbidity and mortality. The morbidity
      of life-threatening infection is reflected in the development of the multiple
      organ dysfunction syndrome (MODS), so the availability of reliable and valid
      tools to quantify MODS is an important prerequisite for the evaluation of
      treatment of patients with infection. In general terms, outcome measures in
      clinical trials are used to answer one of two questions--does the intervention
      work (is a biological effect evident?) and does the intervention help? (is there
      evidence of clinical benefit?) The requirements for measures differ. Measures of
      biological effect should be sensitive, continuous variables, while those of
      clinical benefit should be robust and unequivocally relevant. We describe a
      model, based on our previously published MOD score (a measure of biological
      effect) that permits evaluation of both biological effect and clinical benefit,
      using readily available and commonly measured variables. Such a measure is
      potentially useful in evaluating the effects of new treatments, and in
      understanding the interactions of the biological process of MODS and its familiar
      clinical signs.

PMID- 10890238
TI  - Immunological monitoring of the inflammatory process: Which variables? When to
      assess?
AB  - Monitoring the immune responses in critically ill patients helps us to understand
      pathophysiological aspects of inflammation, immune deficiency, and infection, and
      to assess objective measures of therapeutic success. Monitoring should be adapted
      to the individual therapeutic approach. We recommend the measurement of
      substances in plasma that indicate systemic inflammatory processes, such as
      tumour necrosis factor (TNF), interleukin (IL)-6, and C-reactive protein (CRP),
      and invasive infection or endotoxaemia, such as procalcitonin (PCT). Moreover, it
      is important to evaluate the functional activity of the immune system, which can
      fail like other organs in the process of multiple organ failure. The resulting
      immunodeficiency results in failure to eliminate invading pathogens. Plasma
      concentration of IL-10 and of monocytic function and phenotype (HLA-DR+, CD14+
      monocytes, ex vivo TNF secretion capacity) are the most valuable measurements for
      this purpose.

PMID- 10890239
TI  - Relation of the bi-allelic NcoI restriction fragment length polymorphism within
      the tumour necrosis factor B gene to the development of mediastinitis.
AB  - During recent years the dual role of endogenous inflammatory mediators such as
      tumour necrosis factor (TNF) has become evident. While TNF has been recognised to
      possess a great detrimental potential, for example in the case of sepsis, it is
      on the other hand an integral component of an adequate immune response to
      bacterial invasion. These different properties of TNF and others seem to be
      dependent mainly on the quantitative extent of their formation. Some recent
      findings indicate that this extent may in part be determined genetically. The
      classification of patients according to polymorphic cytokine genes might,
      therefore, predict some of their reactions to septic challenges.

PMID- 10890240
TI  - Concept of and preliminary trial protocol for adjuvant treatment of mediastinitis
      with immunoglobulins after cardiac surgery (ATMI): response to comments and
      criticism.
AB  - During the consensus-based process of protocol development external experts were
      invited to comment on a proposal for a trial protocol on adjuvant immunotreatment
      of patients with wound infection after median sternotomy (ATMI). Controversies
      and arguments can be divided into five main areas: 1) rationale and objectives;
      2) criteria for patient selection; 3) adjuvant treatment; 4) measures of
      efficacy; and 5) course and timetable of the study. We present and summarise the
      experts comments and criticism as well as the result of the final discussion of
      the study group with respect to these areas.

PMID- 10890241
TI  - Adjuvant treatment of mediastinitis with immunoglobins (Pentaglobin) after
      cardiac surgery (ATMI): study protocol.

PMID- 10890242
TI  - The social development of children with severe learning difficulties: a case
      study of an inclusive education initiative between two primary schools in
      Oxfordshire, UK.
AB  - This case study of primary age children in two linked Oxfordshire schools
      investigated the contribution of staff attitudes and practices to inequalities in
      education, and contrasted the socialisation of children with similar learning
      difficulties in different educational placements. Participant observation of a
      group of children and carers in a special school suggested areas of more rigorous
      inquiry. Structured observations compared this group with a matched sample of
      children with similar learning difficulties in a mainstream setting. Staff on
      both sites were invited to comment on findings arising from analysed data in
      order to identify attitudes and policies which might account for the observed
      differences in practice. The study was engendered by experience of differences
      arising from educational placement. The theoretical stance arose through
      reviewing previous work, predominantly the debate on inclusive education, and the
      wider issues of human rights and equal opportunities embedded in the social
      development of people with disabilities. The theoretical framework underpinning
      this study is established in some depth. The project was designed to investigate
      issues of the wider social perspective, by conducting a micro-study of one model
      of educational inclusion whose outcomes have direct relevance to those issues.

PMID- 10890243
TI  - Observational learning in children with Down syndrome and developmental delays:
      the effect of presentation speed in videotaped modelling.
AB  - Children with severe developmental delays (three with Down syndrome and three
      with autism as the primary diagnosis) observed a videotaped model performing two
      basic dressing skills without prompting, verbal or otherwise, or explanation by
      an instructor. In a within-subjects design, dressing skills that were presented
      at a relatively slow presentation speed through videotaped modelling were
      eventually performed better than those presented at a relatively fast speed.
      These data in combination with evidence from this laboratory that passive
      modelling of basic skills is more effective than interactive modelling (e.g.,
      Biederman, Fairhall, Raven, & Davey, 1998; Biederman, Davey, Ryder, & Franchi,
      1994; Biederman, Ryder, Davey, & Gibson, 1991) suggest that standard
      instructional techniques warrant reexamination both from the basis of
      instructional effectiveness and the efficient use of the allotment of teacher
      time.

PMID- 10890244
TI  - John Langdon Down: the man and the message.
AB  - John Langdon Down was the son of a village grocer. Born in Torpoint, Cornwall, in
      1828, he was the 6th child of religious parents. He worked in the family business
      until he was 18 years old and he then qualified as a pharmacist before ultimately
      entering medical school at the London Hospital. He won numerous medals and prizes
      and immediately after taking his medical degree he was appointed medical
      superintendent of the Royal Earlswood Asylum for Idiots in Surrey. He reformed
      the institution and his efforts at classification resulted in his description of
      what he called Mongolian idiocy. His findings were based on measurements of the
      diameters of the head and of the palate and on his series of clinical
      photographs. He was a pioneer of the use of photography in hospitals. Mongolian
      idiocy became a widely used term but in 1961 a group of genetic experts wrote to
      the Lancet suggesting four alternatives. The editor chose Down's syndrome. WHO
      endorsed this later. Langdon Down was a supporter of liberal causes. He made
      important contributions to medical science, developed a large practice and he
      died a wealthy man in 1896. Normansfield, his private training and educational
      centre, had an international reputation. Only recently has his place in medical
      history been recognized.

PMID- 10890245
TI  - Down syndrome and thyroid disorders: a review.
AB  - Thyroid disorders are common in the Down syndrome population but many specific
      areas of importance remain to be resolved. A detailed review of previously
      published case reports and research studies highlighting the clinical association
      between Down syndrome and thyroid disorders was undertaken. Historical,
      epidemiological, immunological, diagnostic and treatment issues are addressed.
      Recommendations for future management and research are considered.

PMID- 10890246
TI  - The World Association movement for Down syndrome.

PMID- 10890247
TI  - Editorial: physicians as historians.

PMID- 10890248
TI  - Flow cytometry DNA applications in pediatric tumor pathology.

PMID- 10890249
TI  - Absence of lamellar bodies with accumulation of dense bodies characterizes a
      novel form of congenital surfactant defect.
AB  - Two female sibling full-term newborns developed respiratory distress shortly
      after birth, which progressed to respiratory failure. Tracheal lavage
      demonstrated presence of surfactant protein A (SP-A), but little surfactant
      protein B (SP-B), without aberrant surfactant protein C (SP-C). On a lung biopsy
      performed in both infants, prominent type II pneumocyte hyperplasia was evident.
      Through ultrastructural examination an absence of normally formed lamellar bodies
      was determined, with numerous irregular electron dense bodies within the type II
      pneumocytes. These electron dense bodies could also be identified in the alveolar
      spaces and alveolar macrophages. No alveolar tubular myelin was present.
      Abnormally high immunoreactivity for surfactant proteins SP-A, proSP-B, SP-B, and
      proSP-C was demonstrated by light microscopy. Presence of incompletely processed
      immunopositive proSP-B, but not proSP-C was observed in the alveolar lumina. No
      mutations in either the SP-B or SP-C gene were identified by sequence analysis of
      amplified cDNA. We conclude that these siblings exhibit an inherited surfactant
      deficiency characterized by abnormal accumulations of surfactant proteins within
      the pneumocytes. This abnormal accumulation may be due to a primary secretory
      defect, a defect in surfactant phospholipids, or an abnormal interaction between
      the phospholipids and surfactant proteins.

PMID- 10890250
TI  - Pediatric neuroblastic brain tumors containing abundant neuropil and true
      rosettes.
AB  - We have encountered a series of seven unusual neuroblastic pediatric central
      nervous system (CNS) neoplasms with a unique constellation of histologic,
      immunohistochemical, and ultrastructural features. The tumors presented in five
      girls and two boys, ages 1 to 3 years. In six cases the lesions involved the
      frontoparietal region, in one case the tectal plate. The tumors consisted of
      small to medium-sized, round to oval, hyperchromatic cells with poorly defined
      cytoplasmic borders. Cells were found in clusters and cords set in a
      paucicellular fibrillar neuropil matrix. Distinctive, virtually anuclear regions
      of neuropil were scattered throughout the lesions. True rosettes with well-formed
      central lumens often filled with granular debris were present, along with
      perivascular pseudorosettes and occasional Homer-Wright rosettes. Mitoses and
      apoptosis were frequent, but large regions of confluent necrosis were absent.
      Immunohistochemically, the neuropil-like areas as well as the perinuclear
      cytoplasm of many embryonal tumor cells were positive for synaptophysin and
      neurofilament protein. Ultrastructurally, the tumor cells showed microtubule
      containing neuronal processes, some with neurosecretory granules. While the
      lesions were largely glial fibrillary acidic protein (GFAP) negative, there was
      focal GFAP positivity consistent with divergent differentiation in one case. The
      clinical outcome was poor, with five patients dead from their disease 5 to 14
      months after initial presentation and one patient with recurrent disease 7 months
      after resection and chemotherapy. The final patient is alive without recurrent
      disease 30 months after initial presentation. These lesions present distinctive
      histological features within the group of primitive neuroectodermal tumors.

PMID- 10890251
TI  - Absent pulmonary valve with tricuspid atresia or severe tricuspid stenosis:
      report of three cases and review of the literature.
AB  - Absence of the pulmonary valve occurs usually in association with tetralogy of
      Fallot and occasionally with an atrial septal defect or as an isolated lesion.
      Very rarely it occurs with tricuspid atresia, intact ventricular septum, and
      dysplasia of the right ventricular free wall and of the ventricular septum. We
      present the clinical, anatomic, and histologic findings of a new case, and for
      the first time, the data from two patients with absent pulmonary valve and severe
      tricuspid stenosis, who exhibited similar histologic findings. We also reviewed
      the clinical and anatomic data of 24 previously published cases and compared them
      with the new cases. In all three new cases, the myocardium of the right ventricle
      was very abnormal. In the two cases with tricuspid stenosis, large segments of
      myocardium were replaced with sinusoids and fibrous tissue. In the case with
      tricuspid atresia, the right ventricular free wall contained only fibroelastic
      tissue. The ventricular septum in all three patients showed asymmetric
      hypertrophy and in two of the three patients, multiple sinusoids had replaced
      large segments of myocardial cells. The left ventricular free wall myocardium and
      the walls of the great arteries were unremarkable. Our data indicate that
      myocardial depletion involving the right ventricular free wall and the
      ventricular septum and its replacement by sinusoids and fibroelastic tissue occur
      not only in cases of absent pulmonary valve with tricuspid atresia but also in
      cases of absent pulmonary valve with tricuspid stenosis. The degree of myocardial
      depletion varies and is more severe when the tricuspid valve is atretic.

PMID- 10890252
TI  - Cytomegalovirus and human herpesvirus 6, but not human papillomavirus, are
      present in neonatal giant cell hepatitis and extrahepatic biliary atresia.
AB  - The purpose of our study was to confirm reports of an association of human
      papillomavirus (HPV) with neonatal giant cell hepatitis (GCH) and biliary atresia
      (BA), and to expand these studies to include cytomegalovirus (CMV), Epstein-Barr
      virus (EBV), human herpesvirus 6 (HHV6), and parvovirus B19 (PVB19). Frozen
      hepatic tissue was available for polymerase chain reaction (PCR) analysis in 19
      cases of GCH or BA and 8 controls. Nested PCR to detect HPV types 6, 16, 18, and
      33 was followed by 32P hybridization with generic probes. PCR followed by
      hybridization with a digoxigenin-labeled probe was used for all other viruses.
      HPV, EBV, and PVB19 were not detected in cases or controls. Two cases of GCH and
      1 case of BA were PCR positive for CMV; controls were negative. HHV6 was detected
      in 6 cases: 2 GCH, 2 BA, and 2 controls. We conclude that HPV is not associated
      with GCH or BA. Detection of CMV in BA and GCH confirms other reports of this
      association. HHV6 requires further study to determine the significance of a
      positive PCR test in the livers of infants.

PMID- 10890253
TI  - Work-up and diagnosis of pediatric non-Hodgkin's lymphomas.
AB  - Non-Hodgkin's lymphomas (NHL) in children and adolescents represent about 10% of
      childhood cancers. Although the types of NHL commonly seen in this population are
      relatively limited to lymphoblastic lymphomas, Burkitt's and Burkitt-like
      lymphomas, and large cell lymphomas, correct diagnosis and classification are
      essential for optimal therapy. Careful handling of pathologic specimens, along
      with collection of proper materials for ancillary studies such as
      immunophenotyping, cytogenetics, or molecular studies, will aid the pathologist
      in reaching a correct diagnosis. Specific morphologic, immunophenotypic, and
      genetic features of the commonly seen types of pediatric NHL are described.

PMID- 10890254
TI  - Persistent interstitial pulmonary emphysema-like cyst associated with metastatic
      synovial sarcoma.
AB  - Interstitial pulmonary emphysema is characterized by the presence of gas
      dissecting the interstitial tissues of the lung. Clinically, it may be acute or
      persistent, and the latter can be further categorized as localized or diffuse.
      Usually, it appears in preterm neonates with a history of assisted ventilation or
      respiratory distress. Although far from frequent, the localized variety of
      persistent interstitial pulmonary emphysema (PIPE) can develop spontaneously in
      full-term babies or infants without any obvious underlying pulmonary disease.
      Histologically, PIPE is characterized by the presence of uni- and multinucleated
      histiocytes lining the inner surface of the cysts. In this report, we describe a
      15-year-old male with synovial sarcoma (SS) of the right ankle diagnosed 4 years
      previously who developed pulmonary metastasis, one of which presented cystic
      changes with features of PIPE.

PMID- 10890255
TI  - Rizatriptan in the treatment of migraine.
AB  - Rizatriptan is a selective 5-hydroxytriptamine1B/1D receptor agonist that was
      launched in 1998 for the acute treatment of migraine in adults. Based on data
      from 6 large clinical trials in patients > or =18 years of age in whom migraine
      was diagnosed according to International Headache Society criteria, the marketed
      10-mg and 5-mg oral doses of rizatriptan are effective in relieving headache pain
      and associated migraine symptoms. The 10-mg dose is more effective than the 5-mg
      dose. At 2 hours after dosing, up to 77% of patients taking rizatriptan 10 mg had
      pain relief compared with 37% of those taking placebo, up to 44% were completely
      pain free compared with 7% of those taking placebo, and up to 77% were free of
      nausea compared with 58% of those taking placebo (P < 0.05 for all 3
      comparisons). Both doses of rizatriptan are generally well tolerated. In placebo
      controlled studies involving treatment of a single migraine attack, the most
      common side effects (incidence > or =2%) occurred in <10% of patients, typically
      were transitory (2 to 3 hours), and were mild or moderate. Rizatriptan is an
      effective and well-tolerated acute treatment for migraine.

PMID- 10890256
TI  - Leflunomide, a novel immunomodulator for the treatment of active rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic disease affecting 0.8% of the population.
      Nonsteroidal anti-inflammatory drugs reduce the pain and inflammation of RA and
      improve mobility but do not slow the progression of joint damage. Disease
      modifying antirheumatic drugs (DMARDs), which limit potentially irreversible
      joint damage, may influence the course of disease progression. This review
      describes the recently approved DMARD leflunomide, an isoxazole-based
      immunomodulator. Unlike other DMARDs, leflunomide arrests the growth of activated
      lymphocytes by inhibiting the enzyme dihydroorotate dehydrogenase, a critical
      link in the production of uridine monophosphate. Leflunomide is rapidly
      metabolized to the active major metabolite A77 1726, which is responsible for the
      drug's pharmacologic activity. Leflunomide has exerted inhibitory activity in
      animal models of RA. Its clinical efficacy has been demonstrated in a number of
      controlled trials. In two multinational 52-week studies and two 24-week studies,
      all leflunomide-treated patients received an initial loading dose of 100 mg for 3
      days, followed by 20 mg/d. The effects on the signs and symptoms of RA were
      evaluated using the American College of Rheumatology (ACR) 20 responder index,
      tender and swollen joint counts and scores, patients' and physician's global
      assessments, and pain intensity index. Erosions and joint-space narrowing were
      assessed by radiography. Compared with placebo, leflunomide significantly
      improved the signs and symptoms of RA (41%-64% improvement) by ACR 20 responder
      criteria (P < 0.001). Leflunomide, methotrexate, and sulfasalazine were equally
      effective in terms of symptom outcomes. In terms of retarding the progression of
      disease, leflunomide was significantly superior to placebo, with no consistent
      difference from methotrexate or sulfasalazine. In a trial using a combination of
      leflunomide and methotrexate therapy, 53% of patients were responders by ACR 20
      criteria. Adverse effects in RA patients receiving leflunomide included diarrhea,
      elevated liver enzymes, alopecia, and rash. Additional adverse events occurring
      with a frequency >5% included allergic reaction, asthenia, abdominal pain, back
      pain, and hypertension, among others. Thus leflunomide may be used in selected RA
      patients (ie, those starting RA therapy for the first time or failing earlier
      DMARD therapy). However, the product labeling requires monthly monitoring of
      liver enzymes until stable concentrations are reached. Other labeled warnings
      include a risk of immunosuppression and an increased risk of fetal death or
      teratogenic effects in pregnant women. Methotrexate, which is also hepatotoxic,
      is usually the initial DMARD recommended for use in patients with aggressive RA.

PMID- 10890257
TI  - The safety profile and antiviral activity of the combination of stavudine,
      didanosine, and nelfinavir in patients with HIV infection.
AB  - We assessed the safety profile, tolerability, and antiviral effect of 12 weeks of
      triple combination therapy with stavudine (d4T), didanosine (ddI), and nelfinavir
      in patients who had not previously received therapy with d4T, ddI, or a protease
      inhibitor. We also assessed the effect of the buffered tablet formulation of ddI
      on the pharmacokinetics of nelfinavir. The study had a single-arm, open-label
      design and enrolled patients aged > or =18 years who had HIV infection and > or
      =10,000 plasma HIV RNA copies/mL. Patients received the full recommended doses of
      oral d4T, ddI, and nelfinavir. Efficacy was assessed in terms of change from
      baseline in plasma HIV RNA and CD4+ cell counts, as well as in terms of the
      proportion of patients achieving HIV RNA levels <400 copies/mL. The first 10
      patients enrolled in the study were included in a substudy to determine the
      effects of the buffered tablet formulation of ddI on the pharmacokinetic profile
      of nelfinavir. A dose of ddI was given 1 hour before nelfinavir, after which the
      maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the
      concentration-time curve (AUC) of nelfinavir were determined. A total of 22
      patients entered the trial, of whom 1 (5%) had AIDS, 12 (55%) had symptomatic HIV
      infection, and 9 (41%) were asymptomatic. The median baseline CD4+ cell count was
      315 cells/microL (range, 70-709 cells/microL), and the median plasma viral load
      was 4.8 log10 copies/mL (range, 4.0-5.6 log10 copies/mL). ddI had no clinically
      significant effects on the plasma pharmacokinetics of nelfinavir. At the end of
      12 weeks of treatment, the mean (+/- SE) decrease in plasma viral load was 1.36+/
      0.24 log10 copies/mL, and 8 of 16 patients (50%) achieved plasma HIV RNA levels
      <400 copies/mL; the mean (+/- SE) increase in CD4+ cell count was 111.4+/-31.7
      cells/microL. Patients who were judged to be compliant with antiretroviral
      therapy (ie, who missed <7 days of all 3 study drugs during 12 weeks of
      treatment) experienced mean decreases in viral load exceeding 2.0 log10
      copies/mL, and 6 of 7 patients achieved HIV RNA levels <400 copies/mL after 12
      weeks of therapy. Although 95% of patients reported an adverse event of grade 1
      or higher, only 1 patient experienced a grade 3 or 4 adverse event (maculopapular
      rash) related to nelfinavir. As reflected in the Cmax, Tmax, and AUC,
      administration of ddI 1 hour before nelfinavir did not influence the
      pharmacokinetic profile of the protease inhibitor. Triple drug therapy with d4T,
      ddI, and nelfinavir was well tolerated and associated with few clinically
      significant toxicities. This treatment resulted in substantial reductions in
      viral load and improvements in CD4+ cell count over 12 weeks.

PMID- 10890258
TI  - Comparison of single-dose fosfomycin and a 7-day course of nitrofurantoin in
      female patients with uncomplicated urinary tract infection.
AB  - This multicenter clinical trial compared single-dose fosfomycin tromethamine with
      a 7-day course of nitrofurantoin for the treatment of acute uncomplicated lower
      urinary tract infection (UTI) in female patients. Healthy females with symptoms
      of acute uncomplicated UTI were enrolled in a double-masked, randomized clinical
      trial. Assessable patients had >10(5) colony-forming units per milliliter of a
      uropathogen in a clean-voided midstream urine sample. Patients received a single
      3-g dose of fosfomycin tromethamine plus 7 days of placebo capsules or a single 3
      g dose of placebo plus 7 days of nitrofurantoin monohydrate/macrocrystal 100-mg
      capsules. Treatment efficacy was assessed by both bacteriologic and clinical
      response 5 to 11 days after the initial treatment dose (visit 2) and 5 to 11 days
      (visit 3) and 4 to 6 weeks (visit 4) after the last day of medication. Of the 749
      patients initially enrolled in the study, 375 received fosfomycin and 374
      received nitrofurantoin. There were no clinical differences in patient
      characteristics between the 2 groups at study entry. Overall, 94% of pretreatment
      isolates were susceptible to fosfomycin and 83% were susceptible to
      nitrofurantoin. Bacteriologic cure rates at the first follow-up visit (5 to 11
      days after initiation of treatment) were 78% and 86% for fosfomycin and
      nitrofurantoin, respectively (P = 0.02). At visit 3 (1 week posttreatment), they
      were 87% and 81% for fosfomycin and nitrofurantoin, respectively (P = 0.17). Both
      treatment groups had an 80% overall clinical success rate (cure and improvement).
      Twenty patients (5.3%) who received fosfomycin and 21 patients (5.6%) who
      received nitrofurantoin reported an adverse effect related to study medication.
      The most common side effects related to fosfomycin treatment were diarrhea
      (2.4%), vaginitis (1.8%), and nausea (0.8%). Both bacteriologic and clinical cure
      rates observed with a single 3-g dose of fosfomycin were comparable to those
      achieved with a 7-day course of nitrofurantoin in female patients with acute
      uncomplicated UTI.

PMID- 10890259
TI  - Comparison of cefdinir and penicillin for the treatment of streptococcal
      pharyngitis. Cefdinir Pharyngitis Study Group.
AB  - Cefdinir, an oral cephalosporin active against Streptococcus pyogenes (group A
      beta-hemolytic streptococci [GABHS]), is also resistant to degradation by most
      oropharyngeal beta-lactamases. This multicenter, randomized, controlled, double
      masked study assessed the tolerability and efficacy of 2 dosing regimens of
      cefdinir in the treatment of pharyngitis due to GABHS. Adults and adolescents
      with pharyngitis due to GABHS received cefdinir 600 mg QD, cefdinir 300 mg BID,
      or penicillin V 250 mg QID each for 10 days. A throat culture and clinical
      assessment were obtained 4 to 9 days after completion of therapy. Of 919 patients
      enrolled, 644 (70.1%) were microbiologically assessable. The eradication rates 4
      to 9 days after completion of therapy were 91.4% in the cefdinir QD group, 91.7%
      in the cefdinir BID group, and 83.4% in the penicillin group (P = 0.02 for
      cefdinir QD vs penicillin, P = 0.01 for cefdinir BID vs penicillin, P = 0.95 for
      cefdinir QD vs cefdinir BID). Clinical cure rates were also superior with
      cefdinir QD (94.8%, P = 0.02) and cefdinir BID (96.3%, P < 0.01) compared with
      penicillin (88.9%). Diarrhea was more common in the cefdinir groups (P < 0.001).
      Seventeen cefdinir patients and 4 penicillin patients discontinued therapy
      because of adverse reaction (P = 0.13). Ten days of treatment for streptococcal
      pharyngitis with cefdinir QD or BID is superior to treatment with penicillin V
      for the eradication of GABHS from the pharynx, although it is associated with a
      higher rate of adverse reactions.

PMID- 10890260
TI  - Pharmacokinetics and pharmacodynamics of aztreonam administered by continuous
      intravenous infusion.
AB  - The pharmacodynamic parameter that appears to correlate best with a successful
      therapeutic outcome with beta-lactam antibiotics is the length of time the serum
      antibiotic concentration remains above the minimum inhibitory concentration (MIC)
      for the infecting pathogen. By maximizing this parameter, continuous
      administration of beta-lactam and related antibiotics by intravenous infusion
      could represent the optimal mode of drug administration. The pharmacokinetic and
      pharmacodynamic properties of ceftazidime administered by continuous intravenous
      infusion have been evaluated previously. Aztreonam is a monobactam antibiotic
      with similar pharmacokinetic and microbiologic activity to that of ceftazidime.
      This study evaluated the pharmacokinetic and pharmacodynamic characteristics of
      aztreonam administered as a continuous intravenous infusion in healthy volunteers
      against multiple clinical isolates. Five men and 3 women received 6 g of
      aztreonam administered by continuous intravenous infusion over 24 hours. Blood
      samples were collected before the infusion and at 0.5, 1 through 8, 12, 18, and
      24 hours after the start of the infusion. Pharmacokinetic parameters were
      determined by standard equations. In vitro susceptibility testing was performed
      using National Committee for Clinical Laboratory Standards guidelines for 4
      clinical isolates of gram-negative bacteria (2 each of Escherichia coli and
      Pseudomonas aeruginosa). Serum inhibitory titers (SITs) were determined in
      duplicate for each clinical isolate at 0 and 24 hours. The subjects' mean (+/-
      SD) age was 29.3+/-4.4 years; mean weight, 74.6+/-14.0 kg; and calculated mean
      creatinine clearance, 107+/-13 mL/min. For the pharmacokinetic parameters, mean
      (+/- SD) values were as follows: steady-state serum concentration, 40.9+/-8.8
      microg/L; half-life, 1.5+/-0.4 hours; elimination rate constant, 0.50+/-0.13
      hours(-1); steady-state volume of distribution, 0.18+/-0.04 L/kg; and total body
      clearance, 6.1+/-1.2 L/h. The MICs were 0.0625 and 0.125 microg/mL against the 2
      E coli isolates and 4 microg/mL against both P aeruginosa isolates. The median
      SITs against the E. coli isolates were 1:256 and 1:512, and against the P.
      aeruginosa isolates were 1:8 and 1:16. At steady state, II subjects had serum
      concentrations of aztreonam > or =4 times the MIC for each organism. These
      findings suggest that further clinical study of the administration of aztreonam
      by continuous intravenous infusion is warranted.

PMID- 10890261
TI  - The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo
      study.
AB  - Grapefruit juice is an inhibitor of cytochrome P-450 3A4 (CYP3A4). This study was
      designed to assess the in vitro and in vivo effects of grapefruit juice on
      sertraline metabolism. The in vitro assay involved analysis of sertraline
      metabolism by CYP3A4 using CYP3A4-expressed human beta-lymphoblast microsomes.
      The in vivo study involved high-performance liquid chromatographic analysis of
      serum trough levels of sertraline and desmethylsertraline in 5 patients who had
      been taking their usual dose of sertraline for > or =6 weeks, followed by
      concurrent use of sertraline with grapefruit juice for 1 week. The in vitro assay
      demonstrated that grapefruit juice inhibited the formation of desmethylsertraline
      in a dose-dependent manner. In the in vivo study, mean serum sertraline levels
      were determined in 5 patients with a history of depression (4 males and 1
      female). The mean age of the patients was 68.6 years, their mean weight was 69.6
      kg, and their mean sertraline dosage was 55 mg/d. The results of the in vivo
      study appeared to be consistent with the in vitro findings, in that mean (+/- SD)
      serum sertraline trough levels increased significantly from 13.7+/-4.9 microg/L
      before to 20.2+/-4.4 microg/L (P = 0.047) after administration of grapefruit
      juice. Thus the in vitro study demonstrated that grapefruit juice can inhibit the
      metabolism of sertraline. A larger study is warranted to substantiate the
      clinical significance of the in vivo findings.

PMID- 10890262
TI  - Comparison of topical nedocromil sodium and oral terfenadine for the treatment of
      seasonal allergic conjunctivitis.
AB  - This double-masked, comparative, multicenter study was conducted to assess the
      onset of action and tolerability of nedocromil sodium 2% ophthalmic solution BID,
      60-mg terfenadine tablets BID, and placebo in the treatment of seasonal allergic
      conjunctivitis. Two hundred sixty-eight patients in whom seasonal allergic
      conjunctivitis was diagnosed were assigned to 1 of 3 groups and administered
      study medication for 4 weeks. Patients' mean age was 33 years (range, 12 to 68
      years); 57.8% (155 of 268) were female. Demographic characteristics were similar
      in all 3 groups. Although all 3 groups showed improvement in ocular symptoms,
      nedocromil sodium was associated with a statistically significantly faster onset
      of action than was terfenadine or placebo (P = 0.038). During the study, 29
      nedocromil sodium-treated patients (36.7%) achieved control of symptoms in < or
      =2 minutes, and 61 (77.2%) achieved control in < or =15 minutes. The
      corresponding numbers were 21 (24.7%) and 50 (58.8%) in the terfenadine group and
      25 (29.1%) and 48 (55.8%) in the placebo group. The frequency of adverse events
      was low and similar between groups (nedocromil sodium, 26; terfenadine, 32;
      placebo, 32). No severe treatment-related adverse events were reported. In
      conclusion, nedocromil sodium had a significantly faster onset of action than did
      terfenadine or placebo.

PMID- 10890263
TI  - Testing patients' lungs: spirometry as part of the physical examination.
AB  - Spirometric measurements of lung function are vital signs that unfortunately are
      not as widely used as blood pressure or cholesterol testing. Spirometry is an
      uncomplicated procedure that can easily be incorporated by primary care
      physicians into routine physical examinations, especially now that simple
      handheld spirometers suitable for all offices are available. Abnormal spirometric
      patterns can alert physicians to patients' additional risk of developing chronic
      lung disease and to the need for interventions that prevent or forestall
      morbidity and mortality. Spirometry also is an important tool for monitoring
      patients' response to therapy in a number of disorders (eg, asthma). Spirometric
      testing in adults should begin at age 40 for smokers and patients with
      unexplained dyspnea, cough, wheezing, or excessive mucus. Children with asthma
      and cystic fibrosis should be identified and followed with spirometry.

PMID- 10890264
TI  - Which statin is most efficient for the treatment of hypercholesterolemia? A cost
      effectiveness analysis.
AB  - A review of the cost-effectiveness literature indicated that the
      hydroxymethylglutaryl coenzyme A-reductase inhibitor fluvastatin is more cost
      effective for achieving minor-to-moderate reductions in low-density lipoprotein
      cholesterol (LDL-C) levels than 3 other statins: lovastatin, pravastatin, and
      simvastatin. The main goal of this study was to verify the applicability of these
      conclusions to Spanish health care costs and patterns of resource consumption
      related to the treatment of hypercholesterolemia. A stochastic simulation model
      was used to predict both the costs and effects of treating high-risk
      hypercholesterolemic patients with fluvastatin, lovastatin, pravastatin, or
      simvastatin. Epidemiologic data were used to find a suitable theoretic
      probability distribution model for baseline LDL-C values in high-risk
      hypercholesterolemic patients. The model was then used to generate 10,000 random
      observations of baseline LDL-C values; the corresponding LDL-C values after a 2
      year treatment period were predicted as a function of the baseline value and the
      percentage reduction expected with a particular statin and dose, according to the
      results obtained in 2 meta-analyses. The probability of treatment discontinuation
      was also taken into account using estimates obtained in usual practice. The
      effects of treatment were expressed as the rate of success in achieving the goal
      level of LDL-C, as defined in the current Spanish recommendations for the
      treatment of hypercholesterolemia. The average costs of treatment were computed
      from both the social and public-financing perspectives, including the cost of
      lipid-lowering drugs, physician visits, laboratory tests, and days off work, as
      appropriate. The occurrence of nonscheduled visits and workdays lost because of
      side effects were taken into account to compute indirect costs relevant to the
      social perspective. The potential costs of treating side effects were ignored. A
      cost-effectiveness analysis was performed to compare the cost-effectiveness
      ratios obtained with each of the 4 statins considered in this study. Model-based
      predictions of the effects, total costs, and cost-effectiveness ratios were made.
      Cost-effectiveness ratios were interpreted as the cost per patient meeting the
      goal of therapy, according to current Spanish recommendations. The data showed
      that fluvastatin had the lowest cost-effectiveness ratios when LDL-C levels
      required reduction to < or =25% of baseline levels. In this situation,
      fluvastatin was more cost-effective than lovastatin, pravastatin, or simvastatin
      from public-financing and social perspectives.

PMID- 10890265
TI  - Suboptimal use of antidepressants in the elderly: a population-based study in
      Nova Scotia.
AB  - This descriptive, retrospective, population-based study assessed patterns of
      antidepressant medication use in elderly patients in Nova Scotia during fiscal
      years 1993 through 1996. Individuals > or =65 years of age who were registered
      with Nova Scotia's Seniors Pharmacare program and filled a prescription for an
      antidepressant medication during the specified period were included in the study.
      We determined the number of individuals who filled > or =1 prescription for an
      antidepressant, the number whose prescription for an antidepressant could be
      matched with a diagnosis of depression in the physician's billing database, the
      number who used antidepressants that were judged inappropriate based on published
      criteria for medication prescribing in the elderly, the number who used a
      therapeutic antidepressant dose based on published dosing guidelines for the
      elderly, and the number who used antidepressants for > or =6 months. A total of
      12,048, 12,317, and 13,419 individuals filled prescriptions for antidepressants
      during the 1993 to 1994, 1994 to 1995, and 1995 to 1996 fiscal years,
      respectively. In each fiscal year, approximately 70% had received a diagnosis of
      depression based on the International Classification of Diseases, Ninth Revision,
      Clinical Modification, making it likely that 70% of antidepressant users were
      receiving these drugs for a primary diagnosis of depression. The number of
      antidepressant prescriptions that were classified as inappropriate for use in the
      elderly was 67% in 1993 to 1994, 61% in 1994 to 1995, and 55% in 1995 to 1996.
      These decreases over time were statistically significant (P < 0.001). Among those
      using serotonin reuptake inhibitors, secondary tricyclic antidepressants, or
      tertiary tricyclic antidepressants, 79%, 45%, and 31%, respectively, appeared to
      be using therapeutic doses. Of 23,553 antidepressant treatment courses, 11,028
      (47%) were for < or =180 days. During the study, a significant number of elderly
      individuals were prescribed antidepressant medications that are judged by expert
      consensus to be inappropriate for use in this population because of an
      unfavorable toxicity profile, although the number declined significantly from
      year to year (P < 0.001 for year-to-year comparisons). Many individuals also
      appeared to be using antidepressant doses that are probably subtherapeutic, but
      this finding seemed heavily dependent on the class of antidepressant used. Nearly
      half of the individuals studied appeared to be treated for inadequately short
      periods.

PMID- 10890266
TI  - Drug utilization reviews of oral quinolone, cephalosporin, and macrolide use in
      nonacute care: a systematic review.
AB  - Drug utilization review (DUR) is a tool for monitoring the appropriateness of
      physicians' prescribing patterns. The present systematic overview was undertaken
      to determine the extent of appropriate use of oral quinolones, cephalosporins,
      and macrolides in nonacute-care settings in North America reported in published
      DUR studies. Potentially relevant DURs conducted since 1987 were retrieved from
      an electronic search of 6 databases (augmented by manual searches of
      bibliographies of appropriate articles) and from personal communications with
      local experts. Independent reviewers applied objective criteria to select the
      DURs for inclusion. Quality assessments were performed by 4 independent reviewers
      using the Edmonton Quality Assessment Tool for Drug Utilization Reviews, an
      instrument developed to assess the potential for systematic bias in a DUR. Data
      from the studies included were abstracted independently by 2 reviewers using a
      standard data-collection form. Twelve of 587 (2.0%) articles met the inclusion
      criteria. Eight studies targeted the appropriateness of prescriptions for
      ciprofloxacin (appropriateness range, 5% to 95%), 3 included cephalosporins
      (range, 0% to 100%), and 2 examined erythromycin (40%). There were 2 primary
      reasons for a rating of inappropriate: (1) the prescription was not first-line
      therapy, or (2) there was insufficient documentation in the patient record. The
      designation inappropriate did not mean that the drug did not benefit the patient.
      Of the 4 intervention-based DURs, 1 study showed a significant improvement in
      appropriate use. Because of heterogeneity in study design, delivery of
      interventions, and outcome assessment, a pooled estimate of effect was not
      derived. Four studies estimated the cost of inappropriate prescribing to the
      institutional study site, which ranged from $20,500 to $173,359 annually;
      however, these estimates cannot be generalized because of various limitations.
      When the 12 studies were assessed for methodologic quality, 1 study was rated as
      high, 7 as moderate, and 4 as low. Levels of prescribing appropriateness reported
      in the DUR literature should be interpreted cautiously. The DUR studies included
      in this review varied greatly in the methodologic rigor applied to sample
      selection, standardized data collection, application of standardized screening
      criteria, and validated data analysis.

PMID- 10890267
TI  - Effectiveness of antihyperlipidemic drug management in clinical practice.
AB  - Although randomized clinical trials have convincingly shown the efficacy of
      antihyperlipidemic drugs, both discontinuation of antihyperlipidemic drugs and
      failure to achieve goal lipid levels would be expected to attenuate the effect of
      these drugs on reducing the rates of hospitalization for coronary events. This
      study compares the rates of hospitalization and low-density lipoprotein
      cholesterol (LDL-C) levels during and after discontinuation of antihyperlipidemic
      drug therapy. A retrospective cohort study was conducted among 2369 patients at 2
      health maintenance organizations (HMOs) during the period 1988 to 1994. Rates of
      coronary heart disease (CHD)-related hospitalization and non-CHD-related
      hospitalization and the LDL-C levels between 14 and 180 days after the initiation
      or discontinuation of drug therapy were compared for periods of
      antihyperlipidemic drug use and nonuse. The rate ratio for CHD hospitalization
      during periods of antihyperlipidemic drug use compared with periods of nonuse was
      1.02 (95% CI, 0.74 to 1.40), excluding the first 6 months after initiation or
      discontinuation and controlling for patient sex, age, history of CHD,
      hypertension, diabetes, and HMO site. By contrast, the adjusted rate ratio was
      0.70 (95% CI, 0.61 to 0.80) for non-CHD hospitalization. The percentage of
      patients with a history of CHD who achieved LDL-C levels <130 mg/dL was 27% < or
      =6 months after initiation of antihyperlipidemic drug therapy compared with 18%
      during gaps in drug therapy (P = 0.04). This study failed to demonstrate the
      effectiveness of lipid-lowering therapy in reducing CHD hospitalizations in
      community settings, apparently because most recipients either discontinued
      therapy or failed to achieve the desired LDL-C reduction while receiving therapy.
      These results indicate the need for interventions to improve patient compliance
      and management of lipid disorders.

PMID- 10890268
TI  - The impact of race and fractures on mortality in a postmenopausal Medicaid
      population.
AB  - The purpose of this study was to model fractures and survival by age and race in
      a large postmenopausal Medicaid population. All Georgia Medicaid claims were
      abstracted for the years 1992, 1993, and 1994. Claims for postmenopausal women (>
      or =50 years of age) were retained, and patients with fractures were identified
      by International Classification of Diseases, Ninth Revision codes for fracture. A
      survival analysis was conducted using Kaplan-Meier estimators to evaluate the
      effect of fracture, age, and race on 3-year survival. A total of 159,400 white
      and black postmenopausal women were identified. The cohort with fracture totaled
      5933 patients, with femoral fractures constituting 46% of all fractures.
      Discounting those with fracture before the study, the fracture incidence was
      approximately 1.2% in this postmenopausal female cohort. The survival analysis
      suggested that after age was accounted for, black postmenopausal women had a 42%
      increased risk of death within 3 years of fracture, compared with 13% for white
      women. However, postmenopausal black women were approximately 50% less likely to
      experience a fracture, and postmenopausal black women without fracture had better
      survival rates than comparable white women. Mortality crossover and the
      diminished likelihood of fracture mask the true nature of fracture survival in
      postmenopausal black women. Postmenopausal black women with fracture are at
      greater risk of dying than their white counterparts.

PMID- 10890269
TI  - Outpatient costs of osteoporosis in a national health insurance population.
AB  - There are few valid data on the outpatient diagnosis and treatment of
      osteoporosis in Germany, despite the high prevalence of this disease and the high
      costs associated with its complications. We therefore conducted a retrospective
      cohort study to investigate the prevalence of documented osteoporosis and the use
      of health care resources in its outpatient treatment in a representative random
      sample of 7490 patients from the Dresden area who were insured under the national
      health insurance program for a 1-year period from the 3rd quarter of 1993 to the
      2nd quarter of 1994. Documented cases of osteoporosis were identified by
      International Statistical Classification of Diseases, 10th Revision diagnostic
      codes M80 to M82, and the costs of diagnostic services for osteoporosis were
      calculated using a uniform fee schedule. Specific and nonspecific osteoporosis
      medications were classified using a published anatomic-therapeutic-chemical code,
      and their costs were calculated on the basis of pharmacy sales prices. Three age-
      and sex-matched controls without documented osteoporosis (n = 705) were assigned
      for each case patient in estimating the net use of resources. Data for the
      region, as well as age-standardized information for the overall German national
      health insurance system, were calculated. The 1-year prevalence of documented
      osteoporosis in the region was 3.14% (5.20% in women, 0.89% in men), and the age
      standardized prevalence in the German national health insurance system was 2.25%.
      During the study period, 51.1% of the cases and 2.1% of the controls were
      examined by osteodensitometry. Patients received 106 defined daily doses of
      osteoporosis medications during the year; 37.0% of the prescribed daily doses
      were for sodium fluorophosphate/calcium combinations, 4.3% were for sodium
      fluoride, and 7.7% were for calcium alone. Sex hormones and calcitonin each
      accounted for 7.7% of the prescribed daily doses. Only a fraction of
      epidemiologically expected cases of osteoporosis have been identified and
      documented in the outpatient sector. Only approximately 50% of these receive
      osteoporosis-specific therapy, and compliance with therapy is low. To reduce
      osteoporosis-associated fracture rates, which are extremely cost intensive and
      greatly impair patients' quality of life, more consistent treatment is needed.

PMID- 10890270
TI  - Medical Outcomes Study Short Form 36: a possible source of utilities?
AB  - General health-status questionnaires such as the Medical Outcomes Study 36-Item
      Short Form Health Survey (SF-36) are frequently used to measure health-related
      quality of life. The SF-36, in its current form, cannot be used to measure
      individuals' utilities or preferences for their health state. Recently, several
      investigators have explored the possibility of obtaining utilities from the SF
      36. This article reviews the SF-36 survey, selected measures of utility, and the
      differences between health-status and utility measures, with an emphasis on use
      of SF-36 results to derive utility scores. We searched the literature from
      January 1966 to July 1999 using MEDLINE and HEALTHSTAR. The terms SF-36, health
      status instruments, utilities, and preferences were searched to identify studies
      that had used both the SF-36 and a utility-based instrument. We first discuss
      studies that were specifically designed to find a predictive equation to obtain
      utilities from SF-36 scores. We then discuss studies that examined the
      correlation between the SF-36 and a utility-based instrument but that were not
      intended to develop a predictive equation as their primary objective. The studies
      that have tried to derive utilities from the SF-36 using a predictive equation
      have used different methodologies; to date, no reliable method has been
      appropriately validated. The poor correlation reported in most of the studies
      attests to the complex relationship between utility-based instruments and the SF
      36. More work is needed to elucidate if utilities can be obtained from the SF-36.

PMID- 10890271
TI  - Assessment of the impact of fibrates and diet on survival and their cost
      effectiveness: evidence from randomized, controlled trials in coronary heart
      disease and health economic evaluations.
AB  - The fibrates are one of several classes of lipid-reducing agents commonly
      prescribed to reduce hypercholesterolemia and prevent coronary heart disease. In
      today's evidence-based, cost-conscious health care environment, interventions
      promoted by policymakers must provide clear clinical benefits and economic value.
      We assessed the evidence regarding the impact of fibrates and diet on survival
      and the cost-effectiveness of these interventions. A literature search was
      conducted for randomized, controlled trials of diet, fibrates, and heart disease
      that were published after 1971; both primary and secondary prevention clinical
      trials were reviewed, and recent literature reviews and meta-analyses were
      searched. The evidence that diet alone improves survival is poor, although
      specifically increasing intake of polyunsaturated fatty acid (including n-3 fatty
      acids) relative to saturated fatty acid intake may provide some clinical benefit
      in the secondary prevention of coronary heart disease. The cost-effectiveness of
      dietary intervention is also questionable because compliance is extremely poor.
      There is no consistent evidence from primary or secondary prevention trials that
      fibrates improve survival; in fact, fibrates may increase the risk of death from
      noncoronary causes. No consistent data suggest that fibrates are a cost-effective
      therapy. Because diet and fibrates do not appear to improve survival or provide
      value, policymakers should promote the use of alternative drug interventions that
      have consistently been proved to reduce mortality and are cost-effective.

PMID- 10890272
TI  - The solvent-free thermal dehydration of tetritols on zeolites.
AB  - A new alditol dehydration method at high temperatures, in the presence of
      molecular sieves without solvent in an argon atmosphere, is described.
      Investigations on tetritols have been carried out. Products arising after the
      intramolecular and intermolecular elimination of water, with retention or
      inversion of the configuration of asymmetric carbon atoms, were observed.
      Complete analytical separation of reaction products was achieved by means of GLC.
      The chemical structures of the compounds obtained were assigned using co
      injection with standards, GLC-CIMS and GLC-EIMS analyses. Two intermolecular
      dehydration products of tetritols were isolated by HPLC and identified by 1H and
      13C NMR spectroscopy.

PMID- 10890273
TI  - Synthesis of 4-deoxy-4-fluoro analogues of 2-acetamido-2-deoxy-D-glucose and 2
      acetamido-2-deoxy-D-galactose and their effects on cellular glycosaminoglycan
      biosynthesis.
AB  - 4-Deoxy-4-fluoro analogues of 2-acetamido-2-deoxy-D-glucose and 2-acetamido-2
      deoxy-D-galactose were synthesized and evaluated as inhibitors of hepatic
      glycosaminoglycan biosynthesis. 2-Acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4
      fluoro-D-glucopyranose (16) exhibited a reduction of [3H]GlcN and [35S]SO4
      incorporation into hepatocyte cellular glycosaminoglycans to 12 and 18%,
      respectively, of the control cells, at 1.0 mM. Similarly, 2-acetamido-1,3,6-tri-O
      acetyl-2,4-dideoxy-4-fluoro-D-galactopyranose (31) exhibited a reduction of
      [3H]GlcN and [35S]SO4 incorporation to 1 and 9%, respectively, of the control
      cells, at 1.0 mM. Unlike 16, 31 exhibited a reduction of [14C]Leu incorporation
      into cellular protein to 57% of control cells, at 1.0 mM.

PMID- 10890274
TI  - Hydrolysis of low-molecular-weight oligosaccharides and oligosaccharide alditols
      by pig intestinal sucrase/isomaltase and glucosidase/maltase.
AB  - The ability of purified pig intestinal sucrase/isomaltase (SI; EC 3.2.1.10/48)
      and glucosidase/maltase (GM; EC 3.2.1.20) to hydrolyze di- and oligosaccharides
      consisting of D-glucose and D-fructose residues and the corresponding alditols
      was studied. The products, after incubation, reflect different binding patterns
      at both catalytic sites of SI. The active site of the sucrase subunit cleaves
      alpha,beta-(1-->2) glycosidic bonds, and only two monomer units of the substrates
      bind with favorable affinity. Oligosaccharides and reduced oligosaccharides
      containing alpha-(1--6) and alpha-(1-->1) glycosidic bonds are hydrolyzed by
      isomaltase, and for the active site of this subunit more than two subsites were
      postulated. Moreover, different binding sites for various aglycons seem to exist
      for isomaltase. Oligosaccharide alcohols are cleaved at lower rates if the
      reduced sugar residue occupies the aglycon binding site. GM also hydrolyzes alpha
      (1-->1) linkages, but at a lower rate. The enzyme has the ability to bind
      compounds containing residues other than D-glucose. There are indications for
      similarities between GM and the isomaltase subunit of SI in the binding mode of
      oligosaccharides.

PMID- 10890275
TI  - Structural characterization of the pectic polysaccharide rhamnogalacturonan II:
      evidence for the backbone location of the aceric acid-containing oligoglycosyl
      side chain.
AB  - Monomeric rhamnogalacturonan II (mRG-II) was isolated from red wine and the
      reducing-end galacturonic acid of the backbone converted to L-galactonic acid by
      treatment with NaBH4. The resulting product (mRG-II'ol) was treated with a cell
      free extract from Penicillium daleae, a fungus that has been shown to produce RG
      II-fragmenting glycanases. The enzymatically generated products were fractionated
      by size-exclusion and anion-exchange chromatographies and the quantitatively
      major oligosaccharide fraction isolated. This fraction contained structurally
      related oligosaccharides that differed only in the presence or absence of a
      single Kdo residue. The Kdo residue was removed by acid hydrolysis and the
      resulting oligosaccharide then characterized by 1- and 2D 1H NMR spectroscopy,
      ESMS, and by glycosyl-residue and glycosyl-linkage composition analyses. The
      results of these analyses provide evidence for the presence of at least two
      structurally related oligosaccharides in the ratio approximately 6:1. The
      backbone of these oligosaccharides is composed of five (1-->4)-linked alpha-D
      GalpA residues and a (1-->3)-linked L-galactonate. The (1-->4)-linked GalpA
      residue adjacent to the terminal non-reducing GalpA residue of the backbone is
      substituted at O-2 with an apiosyl-containing side chain. Beta3-L-Araf-(1-->5)
      beta-D-DhapA is likely to be linked to O-3 of the GalpA residue at the non
      reducing end of the backbone in the quantitatively major oligosaccharide and to O
      3 of a (1-->4)-linked GalpA residue in the backbone of the minor oligosaccharide.
      Furthermore, the results of our studies have shown that the enzymically generated
      aceryl acid-containing oligosaccharide contains an alpha-linked aceryl acid
      residue and a beta-linked galactosyl residue. Thus, the anomeric linkages of
      these residues in RG-II should be revised.

PMID- 10890276
TI  - Physicochemical behaviour of chitin gels.
AB  - Syneresis of chitin gels formed in the course of N-acetylation of chitosan in
      hydroalcoholic media has been studied. A critical cross-linking density related
      to a critical acetylation degree for which the gel undergoes weak syneresis and
      swells in water was shown (degree of acetylation (DA) 88%). Above this value, the
      weight loss during syneresis increases with DA. Conversely, syneresis decreases
      on increasing the polymer concentration, but disappears at a macroscopic level
      for a polymer concentration close to the critical concentration of entanglement
      in the initial solution. An increase in temperature favours the formation of
      hydrophobic interactions and new inter- and intramolecular hydrogen bondings. Due
      to the weak polyelectrolyte character of chitin, the weight of the gel depends on
      the pH and ionic strength of the media. Swelling-deswelling experiments show that
      the swelling of the gel is not fully reversible in relation with the formation of
      new cross-links during the depletion of the network. Our results reveals that the
      balance between segment-segment and segment-solvent interactions as well as the
      molecular mobility play the major role.

PMID- 10890277
TI  - A QM/MM analysis of the conformations of crystalline sucrose moieties.
AB  - Both ab initio quantum mechanics (QM) and molecular mechanics (MM) were used to
      produce a hybrid energy surface for sucrose that simultaneously provides low
      energies for conformations that are observed in crystal structures and high
      energies for most unobserved structures. HF/6-31G* QM energies were calculated
      for an analogue based on tetrahydropyran (THP) and tetrahydrofuran (THF).
      Remaining contributions to the potential energy of sucrose were calculated with
      MM. To do this, the MM surface for the analogue was subtracted from the MM
      surface for the disaccharide, and the QM surface for the analogue was added.
      Prediction of the distribution of observable geometries was enhanced by reducing
      the strength of the hydrogen bonding. Reduced hydrogen-bonding strength is
      probably useful because many crystalline sucrose moieties do not have
      intramolecular hydrogen bonds between the fructose and glucose residues.
      Therefore, hydrogen bonding does not play a large role in determining the
      molecular conformation. On the hybrid energy surface that was constructed with a
      dielectric constant of 3.5, the average potential energy of 23 sucrose moieties
      from crystal structures is 1.16 kcal/mol, and the population of observed
      structures drops off exponentially as the energy increases.

PMID- 10890278
TI  - Synthesis of 5-thio-L-altrose.
AB  - Treatment of 1,2,3-tri-O-acetyl-5,6-anhydro-D-galactofuranose with thiourea gave
      1,2,3-tri-O-acetyl-5,6-dideoxy-5,6-epithio-L-altrofuranose, acetolysis of which
      gave 1,2,3,6-tetra-O-acetyl-5-S-acetyl-5-thio-L-altrofuranose. Deacetylation of
      the latter gave 5-thio-L-altrose.

PMID- 10890279
TI  - Survival of patients with blood-borne AIDS in Italy.
AB  - BACKGROUND: AIDS represents an important public health problem in Italy. Long
      term health care policy planning requires knowledge about the variability of the
      risk of mortality. The AIDS Surveillance Registry (RAIDS), maintained by the AIDS
      Operational Centre (COA) of the National Health Institute of Italy, provides
      valuable information to study the determinants of survival after diagnosis with
      AIDS. This study aimed to estimate the trends among people infected by the human
      immunodeficiency virus (HIV) through blood-related products. METHODS: Study
      subjects were 595 persons with AIDS whose sole ascertained risk factors were
      either blood transfusions or plasma-concentrate infusions, diagnosed from the
      beginning of the epidemic in 1985 through June 1995 and reported to RAIDS by the
      end of June 1996. The Kaplan-Meier technique was used to estimate the survival
      distribution; log-rank and Wilcoxon tests were both performed to assess the
      effects of demographic and clinical factors. Cox proportional hazards models were
      used to identify those factors independently and significantly associated with
      death: model building and fitting were performed in a stepwise fashion, by using
      the score and martingale residuals, based on a new class of graphical and
      numerical methods developed recently for checking the assumptions underlying the
      model. RESULTS AND CONCLUSIONS: In Italy the median survival time for AIDS
      patients infected by contaminated blood, was estimated to be 12.7 months. In
      univariate analyses it was found that women, younger patients (age < 35) and
      those diagnosed more recently with a higher value of CD4 cell counts (>37 cells
      m(-3)) have better survival. Patients diagnosed with AIDS-associated neurological
      disease (neuro-AIDS), or lymphoma, had a median survival significantly shorter.
      Patients diagnosed in the south of Italy tend to have a survival time shorter
      than patients diagnosed in the north. In a multivariate time-dependent regression
      analysis, only type of AIDS indicator disease, age and calendar time of diagnosis
      proved to be significant prognostic factors. It was not possible to estimate the
      effect of risk category (haemophiliacs versus transfused) due to the lack of
      proportionality in the estimated hazard. In conclusion, survival time is found to
      improve over time, indicating a likely positive effect of better care in treating
      HIV and AIDS patients.

PMID- 10890280
TI  - Estimating birth prevalence of Down's syndrome.
AB  - BACKGROUND: Estimates of maternal age-specific prevalence of Down's syndrome are
      needed for the assessment of environmental factors, for counselling and
      monitoring screening programmes. The estimates should relate to populations of
      women who have not received prenatal screening. This is normally achieved by
      using data collected before the widespread use of screening. The problem of under
      ascertainment in some data-sets has been recognised in the literature, but has
      not been dealt with satisfactorily in the statistical models used to estimate
      live-birth prevalence. METHODS: In this paper we develop a model that takes
      explicit account of under-ascertainment and apply this model to data from nine
      published studies. The primary aim of our analysis is to provide an improved
      model for live-birth prevalence. A secondary aim is to examine the ascertainment
      rates in the nine studies. RESULTS: The proposed model provides a good fit to all
      but one of the nine studies, although exclusion of this study does not affect the
      estimated risks. The estimate of risk weighted across the maternal age
      distribution is 1.41 in 1000 live-births [90% confidence interval (CI) 1.37
      1.49]. DISCUSSION: Comparing this figure with those obtained from published rate
      schedules suggests that the proposed model predicts rates that are some 10%
      higher than those obtained when ascertainment is assumed to be complete in all
      studies. The predicted rates are similar to those calculated when only those
      studies known to have high levels of acertainment are included.

PMID- 10890281
TI  - Cancer registration in Germany: current status, perspectives and trends in cancer
      incidence 1973-93.
AB  - BACKGROUND: A federal law effective in 1995 makes it mandatory for all German
      States to build up population-based cancer registries. Although the law provides
      a model of cancer registration, each State may modify this by State-specific
      regulations, as long as they ensure data exchange between the registries and
      between registries and scientific institutions. The 'Network of German Population
      Based Cancer Registries' constitutes the basis for cooperation among the German
      cancer registries. In order to improve the cooperation between physicians and
      epidemiologists, and to demonstrate the benefits of cancer registration, the
      network published a booklet containing facts on time-trends in cancer incidence
      during the last two decades. METHODS: Information on cancer incidence and
      mortality was derived from the population-based cancer registries of Saarland,
      the former German Democratic Republic (until 1989), the City of Hamburg and the
      region of Munster. Altogether these registries cover a population of about 23
      million. Sixteen types of cancer were selected for the analyses. RESULTS: Major
      increases in cancer incidence were observed for female lung cancer, testicular
      cancer, cancer of the oral cavity, malignant melanoma of the skin and non
      Hodgkin's lymphoma. Incidence rates also increased for cancer of the female
      breast, prostate cancer and colorectal cancer. A decrease was observed for
      stomach and cervical cancer. DISCUSSION: In 1998, only a small fraction of all
      German adults were monitored by a population-based cancer registry, making it
      impossible to work out accurate incidence rates for the whole of Germany. Several
      new cancer registries have been built up recently. Data summaries of existing
      German population-based cancer registries assist in enhancing the completeness of
      new cancer registries.

PMID- 10890282
TI  - Validation of a food-frequency questionnaire using multiple-day records and
      biochemical markers: application of the triads method.
AB  - BACKGROUND: A food-frequency questionnaire (FFQ) used to assess usual food intake
      in Southern France has been validated by the classical means of multiple-day food
      records. To minimise over-estimation of the correlation between the dietary
      assessments by the FFQ and the reference method, which occurs if the random
      errors of questionnaire and reference measurement are positively correlated, a
      triangular comparison, the method of triads, was used. METHODS: We applied the
      triads model by comparing the FFQ with two multiple-day food records and three
      biomarkers. Only 87 subjects were included and completed the protocol. One
      biomarker (beta-carotene) was used for the 87 subjects and two biomarkers
      (urinary nitrogen and potassium) were measured in only 40 subjects. RESULTS: For
      beta-carotene intake assessment, the triad model, including the weighed multiple
      records (PETRA), was the best with estimates of validity coefficient of 0.39
      [confidence interval (CI) 0.18-0.60] for the FFQ, 0.52 (CI 0.24-0.86), for PETRA
      and 0.85 (CI 0.43-1) for plasma levels of the nutrient. For protein and potassium
      intake assessment, the triad model including the estimated multiple records was
      the best only for the estimates of FFQ validity coefficient (0.61; CI 0.28-0.96
      and 0.31; CI 0.09-0.66 respectively). CONCLUSION: Accuracy of the dietary
      assessment methods permitted a satisfactory estimation of the validity
      coefficient for beta-carotene intake by the FFQ, despite a small sample. However,
      the validity coefficients for protein and potassium showed wide CI values,
      indicating that a sample size < 50 subjects appears unsatisfactory for
      validation.

PMID- 10890283
TI  - Unrepresentative, invalid and misleading: are waiting times for elective
      admission wrongly calculated?
AB  - THESIS: The UK Government Statistical Service reports the percentage of elective
      'admissions' that took place in England within 3 months of a patient being added
      to NHS waiting lists. This percentage is calculated from cross-sectional data
      using the total number of elective episodes within a specified calendar period as
      denominator and the number of these enrolled on the waiting list less than 3
      months previously as numerator. This approach assumes that NHS waiting lists are
      closed and stationary populations, and has been widely used by government and non
      government researchers in the UK and elsewhere. ANTITHESIS: Little attention has
      been given to the bias introduced when waiting lists are neither stationary nor
      closed. This paper identifies four groups of patients which are excluded from the
      denominator used by the Government Statistical Service and criticises the
      established method of ignoring left and right censored observations. SYNTHESIS:
      We describe two alternative formulae that would give the same results as the
      Government Statistical Service method if waiting lists were closed and
      stationary, but that also give unbiased results when waiting lists are open and
      non-stationary. They require a limited amount of additional cross-sectional data
      to produce upper and lower estimates of the cumulative likelihood of admission
      among those listed. We recommend the production of unbiased estimates by applying
      period life-table techniques to a complete and consistent set of 'times since
      enrolment'.

PMID- 10890284
TI  - Potential gain in precision and power by matching on strong risk factors in case
      control studies: the example of laryngeal cancer.
AB  - BACKGROUND: To increase the precision and power of case-control studies, controls
      are often matched on age and sex, but rarely on other known risk factors.
      Expensive tests of genetic susceptibility in a case-control study of laryngeal
      cancer made us examine the effect of matching for smoking and alcohol consumption
      on the power and potential size reduction of the required control sample.
      METHODS: According to published smoking and alcohol consumption distributions in
      laryngeal cancer cases and population controls, we simulated 10000 frequency
      matched and unmatched studies. The exposure of interest was distributed according
      to different scenarios concerning its relation with the disease and with smoking
      and alcohol consumption. Studies were analysed with multivariable logistic
      regression. RESULTS: Matching increased the precision and power in all scenarios.
      The gain was most pronounced in scenarios assuming moderate confounding by
      smoking and alcohol consumption. In such scenarios, equivalent precision or power
      was only obtained with three times as many unmatched as matched controls.
      CONCLUSIONS: Matching on strong risk factors may increase the precision and power
      of case-control studies considerably. In studies employing expensive biologic
      testing, matching on known strong risk factors may be cost-effective more often
      than previously thought.

PMID- 10890285
TI  - Comparison of alternative survey methods for sensitive self-reported behaviours
      in a follow-up study of isotretinoin.
AB  - BACKGROUND: Responses to questions on sensitive behaviours can be affected by
      when and how questions are asked. METHODS: Using data from an ongoing survey of
      women taking isotretinoin (a teratogenic drug used to treat acne), we compared
      answers to questions on contraceptive use during therapy among 126966 women who
      had begun treatment in 1990-93. 20503 were randomly assigned to a group which was
      surveyed by telephone at the start of treatment, during treatment and 6 months
      after treatment ended (DAT group). 106463 received a mail survey 6 months after
      treatment ended (AT group). Women who could not be contacted during treatment,
      along with the non-respondents in the AT group, received follow-up surveys by US
      mail, air courier and, if necessary, were called by telephone. RESULTS: The
      response rate was higher in the DAT group (96.4%) than in the AT group (84.8%).
      Among respondents, the odds of reported contraceptive use in the AT group
      compared with the DAT group (asked at 6 months after treatment) was 1.41 [95%
      confidence interval (CI): 1.36-1.46]. However, rates of oral contraceptive (OC)
      use were virtually identical in the two groups. In both groups, women surveyed by
      telephone reported lower rates of contraceptive use than women surveyed by mail.
      In the AT group, a late response was associated with a significantly lower rate
      of contraceptive use. CONCLUSIONS: Both mode of data collection (phone versus
      mail) and time to response affected reported rates of contraceptive use.
      Reasonable assumptions about the effect of non-response could not account for the
      difference between the AT and DAT groups. We found that contacting women during
      their treatment did not increase their reported use of contraceptives.

PMID- 10890286
TI  - Over the counter non-steroidal anti-inflammatory drugs and risk of
      gastrointestinal bleeding.
AB  - BACKGROUND: Independent analyses of data from a case-control study conducted by
      the American College of Gastroenterology (ACG) were performed to evaluate and
      quantify potential risks of gastrointestinal (GI) bleeding associated with use of
      analgesics at over the counter (OTC) doses. METHODS: Information on recent
      (within the past week) use of multiple analgesics, plus data on tobacco, alcohol
      and other factors, were obtained from 627 patients enrolled in the ACG GI
      bleeding registry and from 590 procedure-matched controls. Odds ratios (OR) were
      calculated as the measure of association between GI bleeding and the exposures of
      interest. RESULTS: Risk of GI bleeding was increased 2-3 fold among recent users
      of aspirin, ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) at
      OTC doses, with risk increasing in a dose-related manner. In contrast, no excess
      was found among acetaminophen (paracetamol) users. Alcohol consumption was also a
      risk factor, with doubled risks of GI bleeding among drinkers. DISCUSSION: While
      these study results are not definitive, the findings are consistent with limited
      other data also reviewed, and suggest the need for further epidemiologic research
      to clarify the association between use of NSAIDs at OTC levels and risk of GI
      bleeding, and to determine whether NSAIDs and alcohol may interactively combine
      to enhance risk.

PMID- 10890287
TI  - Attitudes toward marijuana use and drug-free experience: relationships with
      behavior.
AB  - Attitude toward drug-free experience is conceptualized as a psychological context
      for drug use that influences the evaluation of perceived consequences of
      marijuana use. Two studies examined the moderating effect of attitude toward drug
      free experience on relationships between attitudes toward marijuana and drug use.
      In Study 1 (N = 316), attitude toward drug-free experience emerged as a
      significant moderator. Participants with positive attitudes toward marijuana use
      and relatively low attitudes toward drug-free experience used marijuana at the
      highest rates. Study 2 (N = 308) provided a partial replication and extension. In
      a second sample, a quadratic relationship emerged between drug-free experience
      and marijuana use. The interaction between the two attitudes approached
      significance. Among the 47 participants who had used marijuana more than 100
      times in their lifetime, attitude toward drug-free experience moderated the
      relationship between attitude toward marijuana and marijuana-related problems.

PMID- 10890288
TI  - Cognitive behavioral therapy delays relapse in female socially phobic alcoholics.
AB  - The present study was conducted to test the hypothesis that socially phobic
      alcoholics treated with Cognitive Behavioral therapy (CBT) will have better
      drinking outcomes than those treated with Twelve-Step Facilitation therapy (TSF).
      Three hundred ninety-seven treatment-seeking alcoholics with concurrent social
      phobia were compared retrospectively to a matched sample of 397 alcoholics
      without social phobia. Treatment was delivered in an outpatient setting, and
      patients were randomized to either CBT, TSF, or Motivational Enhancement therapy
      (MET). The groups were compared on self-reported drinking measures (e.g.,
      quantity and frequency of drinking, and time-to-event measures) during treatment
      period and monthly for 1 year following treatment. Survival analyses revealed
      that female outpatients with social phobia showed delayed relapse to drinking
      when treated with CBT rather than TSF; the reverse was true for female
      outpatients without social phobia. Survival analyses in male outpatients with and
      without social phobia revealed an opposite trend, though it was not statistically
      significant. These data suggest that Cognitive Behavioral therapy is superior to
      Twelve-Step Facilitation therapy for the treatment of alcohol problems in
      specific populations. namely socially phobic women seeking outpatient treatment.

PMID- 10890289
TI  - Gender and smoking behavior in a worksite smoking cessation program.
AB  - Gender-specific patterns in smoking behavior among 844 men and women who
      participated in a worksite smoking cessation program were explored. Although
      gender did not predict outcome, men and women did differ on a number of smoking
      behaviors and smoking history variables. Male participants smoked cigarettes with
      a higher nicotine content and smoked a greater number of cigarettes per day.
      Females reported having made more previous attempts to quit, less confidence
      about quitting, greater effort to quit, greater worry about smoking-related
      illness, and that they would be less likely to quit on their own if this program
      were not offered. Females did tend to report receiving higher levels of general
      social support, as well as partner support for quitting smoking; however, greater
      support did not lead to higher quit rates. At the 2-year assessment, 14.3% of
      female participants (n = 532) reported abstinence, while 13.5% of male
      participants (n = 312) reported abstinence, when missing data were recoded as
      smoking.

PMID- 10890290
TI  - A comparative analysis of perceived risks and substance abuse among ethnic
      groups.
AB  - This study examined perceived risks and prevalence of alcohol, tobacco, and
      illicit drug use among ethnic groups of Whites, Blacks, and Hispanics; compared
      the extent to which drug use varied among different ethnic groups; explored
      whether or not there were any age and gender differences in drug use among the
      ethnic groups; and made implications of the findings. Comparative analyses were
      conducted by using chi2 to determine the association of independent variables
      (ethnicity, age, and gender) with the dependent variables (alcohol, tobacco, and
      illicit drug use) during lifetime, past year, and past month. Data were derived
      from the 1997 and 1996 National Household Survey on Drug Abuse. Our findings
      indicated that there are differences in perceived risks and reported use among
      ethnic groups, as well as in preferences for particular drugs. Whites are the
      least likely to perceive risks for substance abuse, however, they have the
      highest prevalence of lifetime drug use of most types of drugs (with the
      exception of crack cocaine and heroin), as compared with Blacks and Hispanics.
      The examination of past month categories of drug use shows that Whites had the
      highest prevalence rates of alcohol and smokeless tobacco use. Hispanics were
      more likely to binge, and reported higher prevalence of heavy alcohol use. Blacks
      were more likely than Whites or Hispanics to use crack and heroin in their
      lifetime. Implications were made for future research and drug prevention in
      ethnic populations.

PMID- 10890291
TI  - Clusters of precontemplating smokers defined by the perception of the pros, cons,
      and self-efficacy.
AB  - Western smoker populations contain high percentages of smokers who are not
      motivated to quit. In order to develop self-help smoking cessation interventions
      for these smokers, it is of importance to know whether there are subtypes among
      this group. In the present study, cluster analysis was used to search for
      clusters of precontemplating smokers. The clusters were described by three
      cognitive clustering variables: the pros of quitting, the cons of quitting, and
      self-efficacy expectations. On the basis of earlier studies, three cluster
      solutions were tested: the 3-, 4-, and 5-cluster solutions. To cross-validate the
      findings, data from two independently recruited samples of precontemplating
      smokers were used. Three clusters, which were found in earlier studies in the
      United States, were replicated. In the present study these were called
      Unmotivated Pessimists, Motivated Pessimists, and Disengaged. Two additional
      clusters were identified, which might be typical for the tolerant Dutch smoking
      culture: Unmotivated Optimists and Motivated Optimists. It is argued that the
      replicated types are more nicotine-dependent and resistant to change, and
      represent the hard core smoker population, and that both optimistic types are
      less dependent, less resistant smokers who will quit with increasing societal
      anti-smoking pressure. Longitudinal analyses showed that cluster membership was
      predictive of increases in intention to quit and quitting activity.

PMID- 10890292
TI  - Preventing substance use among Native American youth: three-year results.
AB  - This study developed and tested skills- and community-based approaches to prevent
      substance abuse among Native American youth. After completing pretest
      measurements, 1,396 third- through fifth-grade Native American students from 27
      elementary schools in five states were divided randomly by school into two
      intervention arms and one control arm. Following intervention delivery, youths in
      all arms completed posttest measurements and three annual follow-up measurements.
      Youths in schools assigned to the intervention arms learned cognitive and
      behavioral skills for substance abuse prevention. One intervention arm
      additionally engaged local community residents in efforts to prevent substance
      use among Native American youth. Outcome assessment batteries measured youths'
      reported use of smoked and smokeless tobacco, alcohol, and marijuana. Over the
      course of the 3.5-year study, increased rates of tobacco, alcohol, and marijuana
      use were reported by youths across the three arms of the study. Though cigarette
      use was unaffected by intervention, follow up rates of smokeless tobacco,
      alcohol, and marijuana use were lower for youths who received skills intervention
      than for youths in the control arm. Community intervention components appeared to
      exert no added beneficial influence on youths' substance use, beyond the impact
      of skills intervention components alone. Finally, gender differences were
      apparent across substances, measurements, and study arms, with girls smoking more
      cigarettes and boys using more smokeless tobacco, alcohol, and marijuana.

PMID- 10890293
TI  - Occupational attainment, smoking, alcohol intake, and marijuana use: ethnic
      gender differences in the CARDIA study.
AB  - OBJECTIVES: To evaluate the prospective interrelationship of smoking, alcohol
      intake, marijuana use, and educational and occupational attainment of Black and
      White young adults. METHODS: Logistic or mixed model linear regression were used
      to evaluate relationships between self-reported substance use, ethnicity, gender,
      college graduation, and four measures of occupational attainment. RESULTS:
      College graduation in the next 10 years was negatively associated with smoking
      and marijuana use, but not daily alcohol consumption in all ethnic and gender
      groups. In Whites, marijuana use was associated with less prestigious occupations
      and lower family income, while smoking was unrelated and moderate daily drinking
      was positively associated. In Blacks, marijuana use was generally unrelated to
      occupational measures, while smoking and daily alcohol consumption were
      negatively associated. CONCLUSIONS: Relationships between smoking, marijuana use,
      daily drinking, and occupational attainment were not universally negative in this
      age group. Substance use, particularly smoking, is associated with reduced
      occupational attainment in Blacks compared with Whites after considering
      sociodemographic factors potentially limiting educational progression and
      occupational attainment.

PMID- 10890294
TI  - The predictive utility of drinking refusal self-efficacy and alcohol expectancy:
      a diary-based study of tension reduction.
AB  - The potential tension reduction effects of alcohol may be most appropriately
      tested by examining the role of alcohol related beliefs regarding alcohol's
      anxiolytic properties. The relationship between affective change drinking refusal
      self-efficacy, tension reduction alcohol expectancies, and ongoing drinking
      behavior was examined amongst 57 regular drinkers. Alcohol consumption,
      antecedent, and consequent mood states were monitored prospectively by diary,
      Social learning theory hypothesizes that low drinking refusal self-efficacy when
      experiencing a negative mood state should be associated with more frequent
      drinking when tense. Strong alcohol expectancies of tension reduction were
      hypothesized to predict subsequent tension reduction. Contrary to this
      hypothesis, the present study found that alcohol expectancies were more strongly
      related to antecedent mood states. Only a weak relationship between drinking
      refusal self-efficacy and predrinking tension, and between alcohol expectancy and
      subsequent tension reduction, was evident.

PMID- 10890295
TI  - A latent variable analysis of coexisting emotional deficits in substance abusers:
      alexithymia, hostility, and PTSD.
AB  - The emotional disturbance of substance abusers is often described as an inability
      to identify and express feelings coupled with an excess vulnerability to
      experience negative affect. However, there is only limited empirical support for
      this perspective. To validate this description, we first defined components of
      alexithymia, hostility, and posttraumatic stress disorder (PTSD) derived from
      established measures of each by conducting confirmatory factor analyses based on
      a self-report data set from a clinical sample of 253 alcoholics and drug addicts.
      We then fashioned and tested overarching latent variables representing the three
      aspects of emotional dysfunction (i.e., alexithymia, hostility, and PTSD) and
      finally tested the correlations among these overarching variables. We found a
      strong association between a factor labeled Bottled-Up Emotions and another
      labeled Neurotic Hostility (r = .62) as well as an association between PTSD and
      Bottled-Up Emotions (r = .66). The structure, magnitude, and intercorrelation of
      the latent variables did not depend on the type of psychoactive substance abused.
      These results support the view that features of alexithymia and hostility coexist
      in substance abusers and that this joint deficit is part of a broad disturbance
      across multiple psychological domains including pathological response to
      traumatic stress.

PMID- 10890296
TI  - Validation of the modified Fagerstrom tolerance questionnaire with salivary
      cotinine among adolescents.
AB  - This study was conducted to gain evidence of validity for a nicotine dependence
      measure for adolescent smokers. We hypothesized that the individual item
      responses and the total Fagerstrom Tolerance Questionnaire (FTQ) score would be
      positively correlated with cotinine values. We examined the relationship between
      a seven-item modified FTQ and saliva continine among 131 adolescent volunteers in
      a smoking cessation program. As anticipated, the total FTQ score was related to
      saliva cotinine (r = .40, p < .01), as were six of the seven individual FTQ items
      (p < .05). Our findings provide preliminary evidence that the modified FTQ scale
      is valid and applicable to adolescent smokers.

PMID- 10890297
TI  - Alcohol use and intimate relationships in adolescence: when love comes to town.
AB  - The associations between alcohol consumption and intimate relationships in
      adolescence were examined. Data from a longitudinal study of 1,063 adolescents
      were used to investigate whether (a) alcohol use was a precursor of partnership
      and (b) adolescents tended to change their drinking habits once they became
      involved in a steady relationship. Youngsters who consumed alcohol at the ages of
      14 and 15 were more likely to be involved in an intimate relationship 3 years
      later. Drinking in social settings particularly increased the likelihood of
      having a partner 3 years later. In addition, for males, partnership was
      associated with a smaller increase in alcohol consumption in public drinking
      places compared to the other categories (i.e., adolescents who never had a
      partner vs. adolescents who had no partner at the time of measurement). In
      contrast, the increase in consumption at home was the strongest for young men
      involved in a steady relationship. For females, the differences in changes in
      consumption between the partnership categories were in most cases not
      significant.

PMID- 10890298
TI  - Substance dependence and the use of pro re nata anxiolytic/hypnotic drugs in a
      hospital setting.
AB  - Patients hospitalized for treatment of psychiatric illness commonly receive pro
      re nata (p.r.n.) anti-anxiety and hypnotic agents. The relationship between
      illicit drug use and p.r.n. anti-anxiety/hypnotic drug use in hospitalized
      psychiatric patients has not been extensively examined. The purpose of the
      present study was to examine this relationship. A retrospective review of 99
      randomly selected hospitalized patients abstracted information regarding the
      utilization of p.r.n. anxiolytic and hypnotic medications. Seventy percent of the
      patients surveyed evidenced substance dependence. The substance users utilized
      p.r.n. anxiolytics (t = 2.29, df = 81, p < .05) and bedtime hypnotics (t = 4.23,
      df = 90, p < .0001) more frequently than the nonusers. Hospitalized substance
      abusers appear to continue their substance abuse in the hospital, substituting
      prescription preparations for illicit drugs. Nevertheless, cumulative literature
      now suggests that p.r.n. anxiolytic and hypnotic agents play a critical role in
      the management of aggressive behavior and insomnia in patients hospitalized with
      psychiatric illness.

PMID- 10890299
TI  - Testing the causal role of expectancies in smoking motivation and behavior.
AB  - The causal role of outcome expectancies in smoking motivation and behavior was
      tested in a laboratory experiment. Two expectancy manipulations-Health
      Consequences Expectancy Increase (HC) and Mood Management Expectancy Challenge
      (MM)-were crossed in a 2 x 2 factorial design. One hundred twenty-three heavy
      smokers were randomly assigned to the conditions and shown videotaped interviews
      of smokers and exsmokers followed by an interview that personalized the
      information. Both manipulations produced changes in targeted expectancies on at
      least one of two expectancy instruments. As predicted, only the HC manipulation
      produced increases in motivation to quit smoking and a reduction in smoking 3
      months later. This study provides initial evidence that smoking expectancies play
      a causal role in smoking motivation, consistent with previous research with
      alcohol.

PMID- 10890300
TI  - Utility of thin layer chromatography for detection of opioids and benzodiazepines
      in a clinical setting.
AB  - This study examined the utility of thin layer chromatography (TLC) for detection
      of recent use of opioids and benzodiazepines among drug addicts seeking treatment
      at the Drug Dependence Treatment Centre of All India Institute of Medical
      Sciences, New Delhi, India. Over a period of 5 years (1991-1995), 6,055 urine
      samples were analyzed for opioids (morphine, codeine, buprenorphine,
      dextropropoxyphene, pentazocine) and benzodiazepines (diazepam, nitrazepam) by
      TLC. Out of all the drug tests (n = 9,922) carried out, 24% of the drugs had been
      used during the past 72 hr. Averaged across all drugs, the detection rates
      corresponding to 24, 48, and 72 hr by TLC were 37%, 36%, and 31%, respectively. A
      high percentage of negative TLC results was observed in these samples. Moderate
      sensitivity of the TLC assay procedure, low consumption of drug, short time
      between drug use and urine collection, overreporting by the subjects, and drug
      use history of the subject obtained from multiple sources led to high negative
      results. These findings suggest that all the TLC negative results also need
      further confirmation by an alternative, more sensitive technique in a clinical
      setting. This will make the drug abuse testing program more meaningful.

PMID- 10890301
TI  - Drug use and drinking among students in 36 countries.
AB  - This article summarizes data on alcohol and drug use from studies of high school
      students in 36 countries. Drug use levels varied greatly among countries, but
      alcohol and cannabis were used most often, followed by amphetamines, ecstasy, and
      cocaine. In countries having high levels of cannabis use, the use of other drugs
      was also more common but there were no consistent differences for alcohol. Use of
      various drugs was correlated except for alcohol use, which was related to
      cannabis use only when some countries with low alcohol use levels were removed.
      In general, the studies show that drug use priorities for studies are mainly the
      same in the countries studied.

PMID- 10890302
TI  - Recent important substance-related losses predict readiness to change scores
      among people with co-occurring psychiatric disorders.
AB  - The transtheoretical model posits that contemplating change in substance abuse
      involves weighing the costs of substance use against the benefits. One of the
      common aversive consequences of substance misuse is personal loss. Indeed, higher
      total number of losses of unspecified recency and importance have predicted
      greater motivation to change substance use patterns. A sample of 110 participants
      with co-occurring Axis I psychiatric and substance use disorders completed a
      questionnaire measuring recent important substance-related losses (LOSS-QR) and
      the Brief Readiness to Change questionnaire (RTC). The LOSS-QR yielded scores for
      frequency, importance, and association of substance misuse with recent losses.
      Total recent important substance-related loss scores were positively and
      significantly correlated with total RTC. Hierarchical regression analyses found
      that identifying losses as substance related and important accounted for
      significant amounts of variance in total RTC, and identifying losses as substance
      related predicted precontemplation and contemplation scores. As hypothesized by
      the transtheoretical model, awareness of substance-related losses seems to be
      important for people with comorbid psychiatric disorders contemplating behavior
      change.

PMID- 10890303
TI  - Evaluating two self-help interventions for smokeless tobacco cessation.
AB  - The need for effective, low-cost self-help treatment methods for smokeless
      tobacco (ST) addiction becomes more evident as rates of product use and
      associated morbidities increase. This study evaluated two self-help methods for
      ST cessation. One hundred ninety-eight ST users were randomized into two
      conditions: half received the LifeSign, a credit card-sized computer designed for
      gradual ST cessation, and half received the Enough Snuff self-help manual and a
      video. Subjects in both conditions received telephone support for their quit
      effort. The study was conducted entirely through phone and mail, allowing
      delivery of the intervention to both rural and urban users. Self-reported rates
      of sustained abstinence (no tobacco use at two months and six months) were 24.5%
      for the manual/video condition, and 18.4%, for the LifeSign condition.

PMID- 10890304
TI  - Brief interventions for risk consumption of alcohol at an emergency surgical
      ward.
AB  - Patients admitted to an emergency surgical ward were screened for alcohol
      problems and randomized between an extensive alcohol counseling and a brief
      assessment followed by feedback of risky alcohol consumption. Some 165 patients
      were assessed for risk consumption and followed up 6 to 12 months, and it was
      found that patients in both interventions significantly reduced the amount they
      drank per occasion although they drank as often as before. The patients had also
      moved to a stage more ready to change. No differences in effect were found
      between the interventions. A brief assessment with feedback about risk
      consumption can be done on an emergency surgical ward by the surgical staff with
      a few hours of training and may reduce risky alcohol consumption significantly.

PMID- 10890305
TI  - Addiction as a function of action system properties.
AB  - Generalising from some previous analyses of addiction and introducing the concept
      of an action system which governs all actions which are focused on what Brown
      (1988) calls "hedonic management," we argue that addictions of every kind involve
      an action system that displays high salience, low variety, and low vicariance.
      Addictions also involve what Apter (1982) calls the "paratelic state." A study
      was carried out comparing 31 drug addicts with 29 control subjects in terms of
      action system variables. To measure these variables, we constructed a new
      instrument, the Activity-System Drawing Test, and also used the Telic Dominance
      Scale to measure frequency of paratelic states. Dysphoria was measured by means
      of the BATE (anxiety), IDA-13 (depression), SEI (self-esteem), and TAS-20
      (alexithymia) instruments. Strong significant differences were found between
      groups for both action system variables and dysphoria. This supports the idea
      that addictions emerge from systemic properties of the action system.

PMID- 10890306
TI  - Regulation of serotonin release by GABA and excitatory amino acids.
AB  - Regulation of serotonin release by gamma-aminobutyric acid (GABA) and glutamate
      was examined by microdialysis in unanaesthetized rats. The GABA(A) receptor
      agonist muscimol, or the glutamate receptor agonists kainate, alpha-amino-3
      hydroxy-5-methyl-4-isoxazolaproprionate or N-methyl-D-aspartate were infused into
      the dorsal raphe nucleus (DRN) while extracellular serotonin was measured in the
      DRN and nucleus accumbens. Muscimol produced decreases, and the glutamate
      receptor agonists produced increases in serotonin. To determine if these
      receptors have a tonic influence on serotonergic neurons, glutamate or GABA(A)
      receptor antagonists were infused into the DRN. Kynurenate, a nonselective
      glutamate receptor blocker, produced a small, 30% decrease in serotonin. A
      similar decrease was obtained with combined infusion of AP-5 and DNQX into the
      DRN. The GABAA receptor blocker bicuculline produced an approximately three-fold
      increase in DRN serotonin. In conclusion, glutamate neurotransmitters have a weak
      tonic excitatory influence on serotonergic neurons in the rat DRN. However, the
      predominate influence is mediated by GABA(A) receptors.

PMID- 10890307
TI  - Reciprocal autoreceptor and heteroreceptor control of serotonergic, dopaminergic
      and noradrenergic transmission in the frontal cortex: relevance to the actions of
      antidepressant agents.
AB  - The frontal cortex (FCX) plays a key role in processes that control mood,
      cognition and motor behaviour, functions which are compromised in depression,
      schizophrenia and other psychiatric disorders. In this regard, there is
      considerable evidence that a perturbation of monoaminergic input to the FCX is
      involved in the pathogenesis of these states. Correspondingly, the modulation of
      monoaminergic transmission in the FCX and other corticolimbic structures plays an
      important role in the actions of antipsychotic and antidepressant agents. In
      order to further understand the significance of monoaminergic systems in
      psychiatric disorders and their treatment, it is essential to characterize
      mechanisms underlying their modulation. Within this framework, the present
      commentary focuses on our electrophysiological and dialysis analyses of the
      complex and reciprocal pattern of auto- and heteroreceptor mediated control of
      dopaminergic, noradrenergic and serotonergic transmission in the FCX. The
      delineation of such interactions provides a framework for an interpretation of
      the influence of diverse classes of antidepressant agent upon extracellular
      levels of dopamine, noradrenaline and serotonin in FCX. Moreover, it also
      generates important insights into strategies for the potential improvement in the
      therapeutic profiles of antidepressant agents.

PMID- 10890308
TI  - Serotonin, stress and corticoids.
AB  - There is evidence for stressor- and brain region-specific selectivity in
      serotonergic transmission responses to aversive stimuli. The aim of the present
      review is to provide an overview of the effects of different acute and
      repeated/chronic stressors on serotonin (5-HT) release and reuptake,
      extracellular 5-HT levels, and 5-HT pre- and postsynaptic receptors in areas
      tightly linked to the control of fear and anxiety, namely the dorsal and median
      raphe nuclei, the frontal cortex, the amygdala and the hippocampus. In addition,
      our knowledge of the impacts of corticoids on serotonergic systems in these brain
      areas is also briefly provided to examine whether the hypothalamo-pituitary
      adrenal axis may play a role in stress-induced alterations in 5-HT
      neurotransmission. Taken together, the data presented reinforce the hypothesis
      that stress affects such a transmission, partly through the actions of
      corticoids. However, we are still left with unanswered, albeit crucial questions.
      First, the question of the specificity of the serotonergic responses to stress,
      with regard to the site of action and the nature of the stressor still remains
      open due to the heterogeneity of the results obtained so far. This could indicate
      that environmental factors, other than the stressor itself, may have enduring
      consequences on 5-HT sensitivity to stress. Second, the question regarding the
      role of stress-elicited changes in 5-HT transmission within coping processes
      finds in most cases no clearcut answer. In keeping with human symptomatology, the
      need to consider the environment (including the early one) and the genetic status
      when assessing the effects of stress on 5-HT neurotransmission is underlined.
      Such a consideration could help to answer the questions raised.

PMID- 10890309
TI  - Dopaminergic sensitivity and prediction of antidepressant response.
AB  - This study was designed to examine neuroendocrine predictors of antidepressant
      response to the selective serotonin reuptake inhibitor (SSRI) paroxetine. We
      assessed the prognostic utility of the apomorphine stimulation test by examining
      the relationship between pretreatment change in growth hormone (GH) following
      apomorphine and acute response to paroxetine treatment. We hypothesized that
      those subjects with most marked pretreatment dopaminergic supersensitivity, as
      manifested by greatest change in GH, would be most likely to show an early
      antidepressant response and would also be more likely to develop manic or
      hypomanic symptoms on paroxetine. Contrary to our hypothesis, greater dopamine
      postsynaptic sensitivity was associated with greater resistance to paroxetine
      treatment. In our sample of 13 subjects with a major depressive episode,
      pretreatment GH response to apomorphine per unit weight was inversely correlated
      with change in Hamilton depression rating scale following 6 weeks of paroxetine.
      Within the group of subjects who showed mood elevation on paroxetine, there was a
      trend towards greater GH response being associated with slower antidepressant
      response. With regard to the development of manic or hypomanic symptoms on
      paroxetine, change in GH per unit weight not did distinguish the two subjects who
      subsequently developed paroxetine-induced hypomania from other subjects. The
      seven subjects with previous antidepressant-induced hypomania did not differ from
      the other subjects in change in GH response per unit weight. The finding that
      subjects who had low dopamine receptor responsivity pretreatment were more likely
      to have an antidepressant response with paroxetine is consistent with recent
      suggestions that the therapeutic effect of SSRIs may be mediated through
      increased dopamine receptor sensitivity in the mesolimbic system. Further work
      assessing pretreatment and post-treatment GH response to apomorphine will help to
      test the hypothesis that low dopamine receptor responsivity predicts
      antidepressant response to SSRIs.

PMID- 10890310
TI  - Behavioural effects of acute tryptophan depletion in healthy male volunteers.
AB  - Acute tryptophan depletion (ATD) studies have been used to assess the role of the
      serotonergic system in various aspects of human behaviour. Changes in mood have
      already been described in selected groups of individuals submitted to ATD. The
      present study was a randomized, double-blind, cross-over trial designed to
      evaluate the effects of ATD on mood, memory, attention and induced anxiety in
      normal male volunteers. Twelve healthy male volunteers were submitted to two
      separate sessions of ATD, 1 week apart. Drinks containing either a balanced
      mixture of amino acids (B) or a similar mixture devoid of tryptophan (T-) were
      administered in each session. Mood was assessed using self-rating scales.
      Attention and memory were assessed using a battery of psychological tests.
      Anxiety induction was carried out using a simulation of public speaking. Blood
      levels of tryptophan were assessed before and after the B and T- drinks. Results
      showed that ATD markedly decreased plasma tryptophan (p < 0.0001). Mood ratings,
      memory and attention were not changed by the T- drink. There was no difference
      among the anxiety levels measured under T- or B mixtures. These data supports the
      notion that ATD does not change mood and cognitive function in healthy subjects.

PMID- 10890311
TI  - The acute effects of amisulpride (50 mg and 200 mg) and haloperidol (2 mg) on
      cognitive function in healthy elderly volunteers.
AB  - In this double-blind, placebo controlled, four-way cross-over trial in 16 healthy
      elderly volunteers, the acute effects of haloperidol 2 mg, amisulpride 50 mg and
      200 mg, were assessed on a range of tests of cognitive function. On each study
      day, cognitive performance was assessed prior to dosing and at 2, 4, 6, 9, 12 and
      24 h after dosing with the following tests from the Cognitive Drug Research
      computerized assessment system: simple reaction time, digit vigilance task,
      choice reaction time, visual tracking, Critical Flicker Fusion, body sway,
      numeric working memory, immediate and delayed word recall, word recognition and
      self-ratings of mood and alertness. Haloperidol showed a general tendency to
      impair performance, and although this did not reach significance compared to
      placebo, for two tasks there were significant impairments with haloperidol
      compared to amisulpride. Amisulpride 50 mg and 200 mg, was not associated with
      impairment. In fact, there was some suggestion of improvement over placebo on
      three measures. The timings of assessment were appropriate for the study
      compounds. Furthermore, in a recent study in which a smaller number of elderly
      volunteers was tested on the same cognitive assessment system, a clear profile of
      acute impairments of haloperidol 3 mg, was identified. This indicates that
      haloperidol 2 mg, is not a sufficient dose to affect cognitive function in the
      elderly, supporting the general absence of effects with this dose in the young.
      Thus, the general absence of cognitive impairments with amisulpride at the doses
      used in this study suggests that this compound does not impair cognitive function
      in the elderly.

PMID- 10890312
TI  - Pharmacokinetics of mirtazapine and lithium in healthy male subjects.
AB  - A substantial proportion of patients diagnosed with depression and treated with
      antidepressants show no or insufficient response. In such patients, lithium is
      often added to the antidepressant for augmentation. The present study
      investigated the possible drug-drug interaction between mirtazapine and lithium
      in 12 healthy male subjects in a randomized, double-blind, placebo-controlled two
      period cross-over design. Subjects meeting the inclusion and exclusion criteria
      were randomly assigned to one of two groups. After an overnight fast, they
      received either a single oral dose of 600 mg lithium carbonate (16 meq Li+) for
      10 days at 08.00 h and a single oral dose of 30 mg mirtazapine at 21.00 h on day
      9 or the same number (n = 4) of placebo capsules and and a single oral dose of 30
      mg mirtazapine at 21.00 h on day 9. At pre-defined times, blood samples were
      drawn for the measurement of mirtazapine plasma concentrations and lithium serum
      concentrations. In addition, psychometric tests were performed and the safety and
      tolerability of the drugs were assessed. The results indicate that mirtazapine
      does not alter the pharmacokinetics of lithium and vice versa. In addition, the
      combination of mirtazapine and lithium appeared to be safe and well-tolerated.
      Extensive psychometric testing after the administration of mirtazapine did not
      reveal any differences on any tests in subjects on lithium and placebo,
      respectively.

PMID- 10890313
TI  - Serotonin autoreceptor function and antidepressant drug action.
AB  - This article briefly summarizes, within the context of a brief review of the
      relevant literature, the outcome of our recent rat microdialysis studies on (1)
      the relative importance of serotonin (5-HT)1A versus 5-HT1B autoreceptors in the
      mechanism of action of 5-HT reuptake blocking agents, including putative regional
      differences in this regard, and (2) autoreceptor responsiveness following chronic
      SSRI administration. First, our data are consistent with the primacy of 5-HT1A
      autoreceptors in restraining the elevation of 5-HT levels induced by SSRIs,
      whereas nerve terminal 5-HT1B autoreceptors appear to have an accessory role in
      this regard. Second, there is an important interplay between cell body and nerve
      terminal 5-HT autoreceptors, and recent findings suggest that this interplay may
      potentially be exploited to obtain regionally preferential effects on 5-HT
      neurotransmission in the central nervous system, even upon systemic drug
      administration. In particular, emerging data suggest that somatodendritic 5-HT1A
      autoreceptor- and nerve terminal 5-HT1B autoreceptor-mediated feedback may be
      relatively more important in the control of 5-HT output in dorsal raphe-frontal
      cortex and median raphe-dorsal hippocampus systems, respectively. Third, 5-HT
      autoreceptors evidently retain the capability to limit the 5-HT transmission
      promoting effect of SSRIs after chronic treatment. Thus, although the
      responsiveness of these sites is probably somewhat reduced, residual autoreceptor
      capacity still remains an effective restraint on large increases in extracellular
      5-HT, even after prolonged treatment. If a further increase in extracellular 5-HT
      is crucial to the remission of depression in patients responding only partially
      to prolonged administration of antidepressants, then sustained adjunctive
      treatment with autoreceptor-blocking drugs may consequently prove useful in the
      long term.

PMID- 10890314
TI  - Postoperative delirium indicating an adverse drug interaction involving the
      selective serotonin reuptake inhibitor, paroxetine?

PMID- 10890315
TI  - What is the clinical significance of the discontinuation syndrome seen with
      clozapine?

PMID- 10890316
TI  - HCV: epidemiology, modes of transmission and prevention of spread.
AB  - Approximately 3% of the world's population has been infected with the hepatitis C
      virus (HCV), which represents about 170 million chronic carriers at risk of
      developing serious complications. Following the introduction of screening of
      blood donors for infection the risk of transmitting HCV by blood products is
      presently at 1/200,000 units distributed. Intravenous (i.v.) drug users are
      currently the main risk group with a prevalence rate of about 80% and a yearly
      incidence varying between 4 and 6%. Vertical and sexual transmissions have also
      been implicated but data are limited and sometimes controversial. The source of
      infection for the 30% of cases without an identifiable risk factor remains to be
      clarified. Prevention of spread includes detailed information of persons at risk
      of being infected, screening of high-risk populations, strengthening of syringe
      exchanges among i.v. drug users and strict application of disinfection procedures
      for all invasive medical equipment.

PMID- 10890317
TI  - Natural history of HCV infection.
AB  - Chronic hepatitis C virus (HCV) infection affects 170 million individuals
      worldwide. These individuals are at risk of developing both hepatological and non
      hepatological manifestations. HCV is usually only fatal when it leads to
      cirrhosis, the final stage of liver fibrosis. Therefore, an estimate of fibrosis
      progression represents an important surrogate end-point for the evaluation of the
      vulnerability of an individual patient. In untreated patients, the median
      expected time to cirrhosis is 30 years; 33% of patients have an expected median
      time to cirrhosis of less than 20 years and 31% will only progress to cirrhosis
      after more than 50 years, if ever. Several factors are associated with fibrosis
      progression rate: duration of infection, age, male gender, consumption of
      alcohol, HIV co-infection and low CD4 count. Non-hepatological manifestations are
      frequent with more than 70% of HCV patients experiencing fatigue or at least one
      extrahepatic clinical manifestation involving primarily the joints, skin and
      muscles. Several immunological abnormalities are frequently observed, including
      cryoglobulins (40%),anti-nuclear antibodies (10%) and anti-smooth muscle
      antibodies (7%). In contrast severe extrahepatic manifestations are rare, with 1%
      for systemic vasculitis.

PMID- 10890318
TI  - HCV genotypes--role in pathogenesis of disease and response to therapy.
AB  - Hepatitis C virus (HCV) shows considerable variation in its genomic structure,
      allowing classification into six main genotypes. Epidemiological studies have
      shown marked differences in genotype distribution by geographical region, and
      between patient groups. Improved understanding of the rate of nucleotide sequence
      mutation in HCV has allowed the approximate time of divergence of major genotypes
      to be estimated, and the origin and spread of the present epidemic of hepatitis C
      to be better defined. Improved methods of genotype definition over the last few
      years have enabled the importance of genotype in the progression of HCV-related
      disease and response to anti-viral therapy to be studied. Present data strongly
      indicates that HCV genotype is an important determinant of response to treatment,
      but the effect of genotype on disease progression has been harder to clarify.
      This is largely due to the absence of model systems of HCV infection, the
      epidemiological differences in patient groups infected with the different
      genotypes, and the lack of good prospective longitudinal clinical data. As a
      result of advances in methodology, and recent results of large clinical trials of
      combination therapy, a knowledge of HCV genotype is now central to the clinician
      in the management of patients with chronic hepatitis C.

PMID- 10890319
TI  - Replication of the hepatitis C virus.
AB  - Infection with the hepatitis C virus (HCV) is a major cause of chronic liver
      disease. HCV is an enveloped plus-strand RNA virus closely related to flavi- and
      pestiviruses. The first cloning of the HCV genome, about 10 years ago, initiated
      research efforts leading to the elucidation of the genomic organization and the
      definition of the functions of most viral proteins. Despite this progress the
      lack of convenient animal models and appropriate in vitro propagation systems
      have hampered a full understanding of the way the virus multiplies. This review
      summarizes our current knowledge about HCV replication and describes attempts
      pursued in the last few years to establish efficient and reliable cell culture
      systems.

PMID- 10890320
TI  - Therapeutic options for HCV--management of the infected individual.
AB  - Patients with chronic hepatitis C infection should be assessed by liver biopsy
      prior to consideration of anti-viral therapy. Patients with histologically mild
      disease should be observed at regular intervals and assessed with a repeat liver
      biopsy after an interval of 3-4 years. Those with severe disease should receive
      early treatment with interferon-alpha and ribavirin. The duration of therapy is
      determined by the genotype of the infecting virus-viral genotypes 2 and 3 require
      only 6 months of treatment but other genotypes should be treated for 12 months.
      Approximately 35-40% of treated patients will respond to therapy with a permanent
      cessation of viral replication and improvement in liver histology. New therapies
      including polyethylene glycol, PEGylated, interferons and combination regimes
      involving amantadine are currently under evaluation and it is hoped that improved
      regimes will be developed in the near future.

PMID- 10890321
TI  - Hepatitis C virus infection: co-infection with HIV and HBV.
AB  - Hepatitis C shares common routes of infection with hepatitis B (HBV) and the
      human immunodeficiency virus (HIV). It is, therefore, not surprising to find that
      some patients with HCV are co-infected with either HIV and/or HBV. Until
      recently, the effects of HIV on HCV infection have not been investigated--sadly
      patients with HIV died long before their liver disease became problematic.
      However, the development of successful therapies for HIV have led to dramatic
      improvements in life expectancy for patients infected with this virus and in
      these patients, with well controlled HIV, it is becoming clear that hepatitis C
      may lead to the early onset of advanced liver disease. The optimal treatment for
      these patients is unknown but it seems likely that combination antiviral therapy
      will be required. The effects of HBV on HCV are also beginning to be investigated
      and, again, it is clear that co-infection leads to more aggressive liver disease
      with the two viruses interacting in poorly defined ways to increase the rate of
      hepatic fibrosis. Management of combined HCV/HBV infection is still under
      investigation and will probably involve combination therapy.

PMID- 10890322
TI  - Complex management issues: management of HCV in the atypical patient.
AB  - Some patients with chronic hepatitis C virus (HCV) infection demonstrate atypical
      features of presentation and clinical course. These features may be due to direct
      or indirect effects of the underlying HCV infection or may be part of a separate
      clinical syndrome. Patients that can be categorized as 'atypical' include
      immunosuppressed individuals (hypogammaglobulinaemic, co-infected with human
      immunodeficiency virus, recipients of solid organ or haematopoietic cell
      transplants, those with associated disease requiring chronic immunosuppressive
      therapy and patients with chronic renal failure on haemodialysis) as well as
      patients with various extra-hepatic (HCV-associated mixed cryoglobulinaemia,
      membranoproliferative glomerulonephritis etc) or autoimmune manifestations. Since
      many of these patients have been excluded from the large trials evaluating the
      efficacy of interferon-alpha alone or in combination with ribavirin, data
      regarding management are limited. In this chapter, the available information
      regarding the treatment of these patients is reviewed and the frequently
      encountered therapeutic dilemmas discussed. Finally, some reasonable therapeutic
      approaches are suggested while the need for controlled studies for these groups
      of patients is emphasized.

PMID- 10890323
TI  - New drugs for hepatitis C virus (HCV).
AB  - Lack of efficacy and significant side effects have severely limited the use of
      interferon-alpha (IFN-alpha) as the standard therapy for non-A non-B hepatitis
      (NANBH) caused by hepatitis C virus (HCV) and alternative, improved therapies are
      urgently sought. Attempts have been made to improve the potency and tolerability
      of IFN-alpha by adjusting dosing regimens, methods of delivery and length of
      treatment. Furthermore, a number of different agents have been used in
      combination wit IFN-alpha and, from these studies, therapeutic options have been
      galvanized by the synergistic effects of IFN-alpha and ribavirin. Nevertheless,
      the majority of patients with HCV still do not sustain lasting therapeutic
      benefit from this combination and continuing research is required to identify new
      therapeutic candidates that will have more potent antiviral activity and less
      severe side effects. This review focuses on the progress that has been made in
      this area and the prospects for new effective therapies in the near future.

PMID- 10890324
TI  - Liver transplantation for hepatitis C virus related cirrhosis.
AB  - Hepatitis C virus (HCV) related chronic liver disease is now the leading cause
      for liver transplantation in many centres. Virological recurrence is inevitable
      following liver transplantation. Excellent patient and graft survival are seen in
      the short-term, equivalent to that in patients transplanted for other causes of
      liver disease. However, histological evidence of disease recurrence or hepatitis
      is present in over half the patients within a year of transplantation, although a
      small percentage develop progressive cholestatic hepatitis with graft loss within
      a year. Cirrhosis can develop in the first year after transplantation and 28% of
      patients have evidence of cirrhosis by 5 years. There is little agreement over
      the factors that predict the recurrence of disease, development of cirrhosis
      within the graft and graft or patient survival. Graft loss due to HCV occurs in
      up to 9% at 5 years and the long-term prognosis may not be comparable to groups
      transplanted for other diseases. Patients with hepatocellular carcinoma may
      benefit from liver transplantation if the tumour is small and without vascular
      invasion. There are, as yet, no clear guidelines regarding the best combination
      of immunosuppressants in patients with HCV but viral clearance has been achieved
      with the use of interferon and ribavirin therapy post-operatively.

PMID- 10890325
TI  - Hepatocellular carcinoma in patients with HCV.
AB  - In most Western countries hepatitis C virus (HCV) is a common risk factor for
      hepatocellular carcinoma (HCC). Many HCCs are multifocal in origin, but HCC may
      also grow as a single hepatic nodule for years before generating satellite or
      distant tumours. HCV may promote cancer through cirrhosis, which is often
      associated with HCV-related HCC, but it might also have oncogenic properties by
      interacting with cellular genes that regulate cell growth and differentiation.
      Treatment of patients with chronic hepatitis C using interferon might attenuate
      HCC risk, particularly in those who respond to therapy. Many patients whose
      cancer is detected early have been successfully treated by liver transplantation
      and have shown significantly prolonged survival. This is less often achieved with
      hepatic resection or regional therapies, which may indeed destroy small tumours,
      without affecting the complications of portal hypertension. Screening remains the
      only realistic approach for improving the treatment of HCC patients, but its cost
      effectiveness is uncertain.

PMID- 10890326
TI  - Treatment of chronic hepatitis C virus infection in children.
AB  - Hepatitis C virus (HCV) infection may occur in infants and children, although it
      is much less common than it is in adults. The main transmission routes include
      mother-to-infant transmission, use of HCV infected blood products, unsterile
      needles or syringes and other invasive procedures. The natural course of HCV
      infection in children is variable: some (20-40%) develop an acute resolving
      infection and spontaneous regression occurs in approximately one-third of infants
      of HCV infected mothers before 2 years of age. Approximately 60-80% of HCV
      infected children develop a chronic infection with varying degrees of activity
      and fibrosis, mostly mild during childhood. However, the potential risks of liver
      cirrhosis and hepatoma during later life are obvious. Interferon is the main
      agent used to treat HCV infection in children. The response to interferon at the
      end of 4-12 months of therapy ranges from 25-90%. A sustained response was found
      in 36-56% of children 6-36 months after the end of therapy. The duration of
      therapy is recommended to be 12 months. At the end of 3 months, an evaluation of
      the response is indicated in the majority of children, except those with
      thalassemia, in whom evaluation of response should be conducted at the end of 6
      months of therapy. The benefit of other therapies, such as combination therapy
      with interferon and ribavirin in children with hepatitis C is currently under
      investigation.

PMID- 10890327
TI  - Conference on complementary medicine.

PMID- 10890328
TI  - The homeopathy debate.

PMID- 10890329
TI  - Massage therapy.

PMID- 10890330
TI  - An examination of the efficacy of Ginkgo biloba extract EGb761 on the
      neuropsychologic functioning of cognitively intact older adults.
AB  - OBJECTIVES: Few investigations have examined the effectiveness of Ginkgo biloba
      extract for enhancing cognitive abilities in individuals with no history of
      significant neurocognitive dysfunction. The purpose of this research was to
      examine the relatively short-term (i.e., 6 weeks) efficacy of Ginkgo biloba
      extract EGb 761 on the cognitive functioning of cognitively intact persons over
      the age of 55 years via a diverse battery of neuropsychologic tests and measures.
      PARTICIPANTS: From the 48 cognitively intact participants between the ages of 55
      and 86 years who initially enrolled in this study, 21 males and 19 females
      successfully completed the study's protocol and provided valid data sets. DESIGN:
      A 6-week, double-blind, fixed-dose, placebo-controlled, parallel-group
      experimental design was utilized. Participants were randomly assigned to either a
      Ginkgo biloba extract EGb 761 (180 mg/d) or placebo control group. To evaluate
      participants' cognitive and behavioral functioning, series of neuropsychological
      tests were administered to them prior to the initiation of the Ginkgo biloba
      extract/placebo therapy (i.e., pretreatment baseline) and again, just prior to
      the termination of the treatment regimen (i.e., after 6 weeks). RESULTS:
      Participants who received 180 mg of Ginkgo biloba extract EGb 761 daily for 6
      weeks exhibited significantly more improvement on a task assessing speed of
      processing abilities (i.e., Stroop Color and Word Test color-naming task) by the
      end of treatment as compared to participants who received placebo. Trends
      favoring improved performances in the Ginkgo biloba group were also demonstrated
      in three of the four remaining tasks that involved a timed, speed of processing
      component, although they did not reach statistical significance. Furthermore, a
      significant relationship was found between the type of treatment (Ginkgo biloba
      extract or placebo) and participants' ratings of their overall abilities to
      remember. Specifically, more participants in the Ginkgo biloba extract group
      rated their overall abilities to remember by the end of treatment as "improved,"
      as compared to the placebo group. In contrast, no significant differences were
      found between the Ginkgo biloba and placebo groups by treatment end on any of the
      four objective memory measures. CONCLUSIONS: Taken together, the findings from
      standardized neuropsychologic assessment and a subjective, self-report
      questionnaire suggested that relatively short-term (i.e., 6 weeks) utilization of
      Ginkgo biloba extract EGb 761 may prove efficacious in enhancing certain
      neurocognitive functions/processes of cognitively intact older adults.

PMID- 10890331
TI  - Medical student interest in alternative medicine.
AB  - BACKGROUND OBJECTIVES: An increasing sector of the American population is seeking
      health services from alternative practitioners and using alternative therapies.
      This study investigated whether medical students perceived that information on
      alternative therapies would be useful to them as future practicing physicians.
      METHODS: A one-page anonymous questionnaire was distributed to the entire first
      year medical class of a large, public, Midwestern medical school during their
      first semester. They responded to a series of five statements concerning
      alternative medicine and medical school coverage of this topic. RESULTS: The
      majority (84%) of students reported that knowledge about alternative medical
      therapies would be important to them as future physicians. The respondents wanted
      to learn about alternative therapies while in medical school (72%), but very few
      thought they would receive adequate exposure to this topic (6%). The majority
      also reported that direct observation of alternative practitioners would be the
      best method of instruction in this area (58%). CONCLUSIONS: The results suggest
      that medical students are interested in learning about alternative medical
      therapies and they perceive this knowledge will be important to them as
      physicians. As medical schools undertake various curriculum reforms they should
      be aware of rising student interest in alternative medical therapies.

PMID- 10890332
TI  - Improvement of C-reactive protein levels and body temperature of an elderly
      patient infected with Pseudomonas aeruginosa on treatment with Mao-bushi-saishin
      to.
AB  - OBJECTIVE: To examine the effectiveness of Mao-bushi-saishin-to (Ma-Huang-Fu-Zi
      Xi-Xin-Tang in Chinese medicine) (Tochimototenkaido Co. Ltd., Osaka, Japan), one
      of the traditional herbal medicines, against resistant bacterial infection.
      SETTING: The Nursing Center Himawari, Izumo, Japan DESIGN, PATIENT, AND
      PREPARATION: Half of the standard dose of Mao-bushi-saishin-to was prescribed for
      7 days to one elderly patient with fever and positive C-reactive protein (CRP)
      levels suffering from drug resistant Pseudomonas aeruginosa. The daily standard
      dose of Mao-bushi-saishin-to is prepared from 1200 mg of dried extract obtained
      from three crude drugs, Ephedrae Herba (4 g), Asiasari Radix (3 g), and Aconiti
      Tuber (1 g). It is certified by the Japanese Ministry of Health and Welfare.
      RESULTS: The patient's fever and CRP level returned to normal levels.
      CONCLUSIONS: In cases in which the fever does not fall in response to antibiotics
      for at least 3 days, half of the standard dose of Mao-bushi-saishin-to for 7 days
      might be worth trying to induce remission, especially for elder patients.

PMID- 10890333
TI  - Can scientific medicine incorporate alternative medicine?
AB  - The authors examine the problem of defining alternative medicine, and after a
      brief analysis conclude that a satisfactory unifying definition of the different
      practices is not possible. Scientific knowledge is a function of scientific
      method. In turn the principle of falsifiability proposed by Karl Popper is used
      as a demarcation line between science and pseudoscience. They assert that the
      various alternative modalities do not represent authentic scientific disciplines,
      as they lack many of the minimum requirements of scientific discourse and, above
      all, because they violate the principle of falsifiability. Until they overcome
      these methodological shortcomings, alternative medical practices cannot become
      authentic scientific disciplines.

PMID- 10890334
TI  - Guidelines for clinical research in complementary medicine.
AB  - There are several stages in preparing clinical research studies. Stage 1 includes
      identifying the purpose of the inquiry and finding the essential financial
      resources. Careful thinking about the clinical practice to be investigated and
      the allocation of time for research is also necessary. Stage 2 involves assessing
      the feasibility of the study. Statistical decisions are best made before data are
      collected, and this means consultation with a statistician or methodologist.
      There has to be ethical approval from the cooperating institution. A thorough
      search of the literature is fundamental. In Stage 3, the final trial is designed,
      ethical approval obtained, and the proposal is submitted for funding. In the
      final stage, Stage 4, the trial is carried out, analyzed, and prepared for
      publication.

PMID- 10890335
TI  - How to evaluate the effectiveness of complementary therapies.
AB  - The most important question about any treatment is whether it is effective. This
      article summarizes basic theoretic and practical aspects that are relevant to the
      evaluation of the effectiveness of a treatment. The factors that can explain why
      patients improve over time and the ways to separate these factors are outlined.
      It is explained why, theoretically, randomized clinical trials are the best
      method to answer questions about effectiveness. Reasons that such trials
      sometimes fail in practice to provide valid answers are listed. It is argued why
      evidence from randomized trials must be "complemented" by a variety of different
      research methods and quality assurance projects.

PMID- 10890336
TI  - Subjective scales for the evaluation of therapeutic effects and their use in
      complementary medicine.
AB  - Using existing systems for appraising the efficacy of various therapies,
      regardless of their typology, the authors considered approximately 10 methods
      commonly used to evaluate quality of life. They provide guidelines on how to
      build another index for judging quality of life, taking into account the
      patient's conditions of life. These indexes share similar problems in finding
      objective measures for assessing personal situations without regard to patients'
      or observers' subjective impressions. Nevertheless, the authors demonstrate that
      for randomized controlled clinical trials and for meta-analyses this deficiency
      is also a problem, at least qualitatively, for scientific methods that are
      considered quite objective. Therefore, according to the methodological manifesto
      of the World Health Organization, the authors conclude by suggesting the
      simultaneous adoption, for complementary medicine studies, of some methods
      already known for their use in conventional medicine, despite general limited
      validity.

PMID- 10890337
TI  - Access to databases in complementary medicine.
AB  - Access to medical databases is a keystone for obtaining up-to-date and complete
      information for physicians. In the last few years, the rapid growth of the World
      Wide Web has given rise to an information revolution, enabling health care
      providers to gain access (often free) to an expanding volume of information that
      was previously inaccessible. Search engines and online databases assist the
      search for health information. In this article we examine the biomedical
      databases of primary interest in the field of alternative and complementary
      medicine, dividing them into Web accessible and nonaccessible databases and
      emphasizing the freely available ones. A further classification is major
      biomedical bibliographic databases specific to complementary medicine, and
      dedicated therapy or modality-specific databases.

PMID- 10890338
TI  - Variables of stimulation and placebo in acupuncture reflexotherapy.
AB  - Placebo can be defined as "the idea of recovery." It represents the natural
      impulse toward recovery that is catalyzed by treatment or even simply by the idea
      of treatment. Therefore, placebo is not an "active" treatment; it is used in
      scientific research to discriminate between the actual effect of a drug or
      therapeutic technique and the result of chance or the will to recover. Even
      though it is only an idea, placebo can cause improvement and recovery in
      approximately 30% of the subjects treated with any therapeutic program and for
      very different pathologies. Acute pathologies are more sensitive to placebo than
      chronic ones; functional disorders respond better than organic alterations, and
      so on. The main controversial issues in the methodology of acupuncture research
      are: placebo, double-blinding, and the intensity of stimulation of needles. The
      most used placebo method is sham acupuncture, which is the insertion of the
      needles outside acupuncture points. It is argued that this methodologically
      incorrect choice leads to studying the importance of the acupuncture point,
      rather than that of acupuncture as a transdermic stimulation technique.

PMID- 10890339
TI  - International research project to devise a protocol to test the effectiveness of
      acupuncture on painful shoulder.
AB  - OBJECTIVES: To describe in detail the questions and deliberations leading to the
      development of a methodologically rigorous protocol to test the effectiveness of
      acupuncture on painful shoulder. DESIGN: Randomized controlled trial using three
      groups, including one control group. SETTINGS/LOCATION: A hospital in the north
      of Italy treating at least 8-10 painful shoulders a day, with
      physician/acupuncturists, physiotherapists, and assessors available to
      participate in the study. SUBJECTS: Sixty patients with monolateral painful
      shoulder. A list of exclusion criteria is given. INTERVENTIONS: Acupuncture +
      mobilization; mobilization alone (control); ear acupuncture + mobilization.
      OUTCOME MEASURES: Severity of pain, scored on a visual analogue scale (VAS) and
      on the McGill Pain Questionnaire and restriction of range of motion (ROM) of the
      shoulder joint. Voluntary use of pain medication, Tenoxicam 20 mg, was added to
      the protocol. RESULTS: The research team developed a protocol and methodology
      that avoids the common flaws and difficulties of previous clinical trials on
      acupuncture. CONCLUSIONS: Physicians and acupuncture specialists will benefit
      from the advice and support of a project group consisting of experienced
      clinicians, researchers, and statisticians when designing and preparing clinical
      trials on acupuncture and other complementary and alternative therapies.

PMID- 10890340
TI  - Childhood risk factors for criminal justice involvement in a sample of homeless
      people with serious mental illness.
AB  - It has been suggested that criminal justice involvement among the homeless,
      particularly those with mental illness, is largely situational. The objective of
      this study was to assess, in a sample of homeless seriously mentally ill people,
      the prevalence of childhood conduct disorder behaviors as a risk factor for adult
      criminal activity as well as the extent and types of adult criminal justice
      contact. Data were taken from the national ACCESS program, which conducted
      extensive baseline interviews with 7,222 homeless seriously mentally ill adults.
      The interview assessed demographics, childhood risk factors for criminal activity
      such as conduct disorder behaviors, foster care, and parental abuse, as well as
      current illness severity and recent criminal justice contact. The 2-month arrest
      rate in this sample was much higher than national rates (11% compared with 1%
      annually in the general population). Although most arrests were for minor crimes
      (10.8%), there were also substantial rates of arrest for major (2.7%) and
      substance-related charges (2.0%). The prevalence of a history of conduct disorder
      behavior was also substantial (55% in male subjects, 40% in female subjects), and
      conduct disorder was a strong predictor of recent criminal justice involvement,
      even after controlling for other predictors of arrest (odds ratio = 1.76 for
      major crimes, 1.49 for minor crimes, and 1.98 for substance-related crimes).
      Recent literature has criticized a trend to criminalize homeless mentally ill
      persons for attempting to get needed food, shelter, or medical attention.
      However, these data indicate that at least some proportion of arrests in this
      population are of people who have been exhibiting antisocial behavior since early
      adolescence, and that early antisocial behavior is a strong predictor of all
      types of recent arrests in this population.

PMID- 10890341
TI  - Individual predictors of traumatic reactions in firefighters.
AB  - Increasingly, theorists and researchers in the area of trauma are pointing to the
      importance of individual differences in resilience and vulnerability as key
      determinants of the intensity and duration of trauma-related symptoms.
      Determining the relative influence of individual predictors is important for the
      further development of theoretical models for understanding trauma responses and
      for the subsequent development of intervention strategies that are sensitive to
      individual differences. This study explores the influence of individual factors
      and social support on traumatic reactions in firefighters exposed to tragic
      events in the line of duty. A total of 164 Australian firefighters completed
      questionnaires targeting locus of control, self-efficacy, patterns of
      interpersonal relating, social support and level of emotional distress. Results
      indicate that individuals with feelings of insecurity, lack of personal control,
      and alienation from others were more likely to experience higher levels of
      depression and posttraumatic stress symptoms subsequent to exposure to traumatic
      events on the job.

PMID- 10890342
TI  - The place of confusional arousals in sleep and mental disorders: findings in a
      general population sample of 13,057 subjects.
AB  - Confusional arousals, or sleep drunkenness, occur upon awakening and remain
      unstudied in the general population. We selected a representative sample from the
      United Kingdom, Germany, and Italy (N = 13,057) and conducted telephone
      interviews. Confusional arousals were reported by 2.9% of the sample: 1% (95%
      confidence interval: .8 to 1.2%) of the sample also presented with memory
      deficits (53.9%), disorientation in time and/or space (71%), or slow mentation
      and speech (54.4%), and 1.9% (1.7% to 2.1%) reported confusional arousals without
      associated features. Younger subjects (< 35 years) and shift or night workers
      were at higher risk of reporting confusional arousals. These arousals were
      strongly associated with the presence of a mental disorder with odds ratios
      ranging from 2.4 to 13.5. Bipolar and anxiety disorders were the most frequently
      associated mental disorders. Furthermore, subjects with Obstructive Sleep Apnea
      Syndrome (OSAS), hypnagogic or hypnopompic hallucinations, violent or injurious
      behaviors, insomnia, and hypersomnia are more likely to suffer from confusional
      arousals. Confusional arousals appears to occur quite frequently in the general
      population, affecting mostly younger subjects regardless of their gender.
      Physicians should be aware of the frequent associations between confusional
      arousals, mental disorders, and OSAS. Furthermore, the high occurrence of
      confusional arousals in shift or night workers may increase the likelihood of
      inappropriate response by employees sleeping at work.

PMID- 10890343
TI  - Gender differences in the associations between posttraumatic stress symptoms and
      problematic substance use in psychiatric inpatient adolescents.
AB  - This study examined gender differences in the associations between posttraumatic
      stress symptoms and problematic substance use in psychiatrically hospitalized
      adolescents. Ninety-five adolescent inpatients (38 boys, 57 girls) were
      systematically evaluated with a battery of psychometrically well-established self
      report measures to assess trauma exposure, posttraumatic stress symptoms,
      problematic alcohol and drug use, and internalizing and externalizing
      psychopathology. Twenty-three percent (N = 22) of patients met DSM-IV-based
      symptom criteria for PTSD, and 37% (N = 35) and 34% (N = 32) of patients endorsed
      problematic levels of drug and alcohol use, respectively. Posttraumatic stress
      symptoms were significantly associated with problematic drug and alcohol use in
      girls but not in boys. There were no significant gender differences in
      posttraumatic stress symptoms and/or problematic substance use, to account for
      the gender differences in the association between PTSD and substance use. Our
      findings suggest that the link between substance abuse and PTSD may be especially
      salient for female adolescents.

PMID- 10890344
TI  - Impact of ethnicity, violence and acculturation on displaced migrants:
      psychological distress and psychosomatic complaints among refugees in Sweden.
AB  - This study uses data collected in 1996 by the Swedish National Board of Health
      and Welfare. By means of interviews with 1980 foreign-born immigrants, an attempt
      was made to determine the impact of a) migration status (country of
      birth/ethnicity), b) exposure to violence, c) Antonovsky's sense of coherence, d)
      acculturation status (knowledge of Swedish), e) sense of control over one's life,
      f) economic difficulties, and g) education, both on psychological distress (using
      General Health Questionnaire 12) and psychosomatic complaints (daytime fatigue,
      sleeping difficulties, and headache/migraine). Iranians and Chileans (age
      adjusted) were at great risk for psychological distress as compared with Poles,
      whereas Turks and Kurds exhibited no such risk. When the independent factors were
      included in the model, the migration status effect decreased to insignificance
      (with the exception of Iranian men). A low sense of coherence, poor acculturation
      (men only), poor sense of control, and economic difficulties were strongly
      associated with the outcomes, generally accounting for a convincing link between
      migration status and psychological distress. Furthermore, a low sense of
      coherence, poor acculturation (men only), poor sense of control, and economic
      difficulties in exile seemed to be stronger risk factors for psychological
      distress in this group than exposure to violence before migration.

PMID- 10890345
TI  - Associations between staff feelings toward patients and treatment outcome at
      psychiatric treatment homes.
AB  - This paper presents, as part of a national Swedish research project, a study of
      associations between staff feelings toward patients and treatment outcome at 23
      small psychiatric inpatient units. The outcome was measured with a composite
      scale based on structured interviews. Staff feelings were reported on a feeling
      checklist. Few and scattered correlations were found between staff feelings and
      treatment outcome when the whole group of patients was analyzed together. More
      meaningful patterns were found when data for psychotic and borderline patients
      were analyzed separately. For psychotic patients, positive outcome was associated
      with low levels of negative feelings throughout treatment. For borderline
      patients, positive outcome was associated with negative feelings at the beginning
      of treatment, followed by strong positive feelings in the later part. Staff
      feelings were more strongly associated with outcome for borderline patients than
      for psychotic patients. Patients with different structural diagnoses need
      different kinds of staff "feeling milieus."

PMID- 10890346
TI  - Incomplete recovery among endogenously depressed patients: an ethological
      analysis.
AB  - The paper reports on an ethological study comparing the behavior of hospitalized
      endogenously depressed (N = 11) and nonpsychiatrically ill control (N = 11)
      subjects hospitalized for somatic illnesses. All subjects participating in the
      study signed the Helsinki Declaration of 1964 for protection of human research
      subjects. Findings include: a) for the first hospital week behavioral differences
      between the two subject groups were highly significant with the most robust
      finding being the reduced frequency of social interaction among depressed
      subjects, b) an increase in communication among depressed subjects over the
      course of hospitalization but a decline of communication and an increase of self
      activity among controls, and c) significant behavior profile differences between
      the two subject groups at the time of hospital discharge. The findings suggest
      that clinically remitted depressives are not fully recovered and socially capable
      when discharged from the hospital.

PMID- 10890347
TI  - Schizophrenic, depressed, and nonpsychiatric medical patients: an ethologically
      based comparison.
AB  - This paper reports on an ethologically based comparison of the behavior of 11
      schizophrenic subjects with the behavior of 11 matched control subjects and 11
      matched endogenously depressed subjects. All subjects were studied while they
      were in inpatient hospital wards. Findings include: a) The behavior pattern of
      schizophrenic subjects deviates significantly from that of control subjects in
      seven behavior parameters; b) the behavior pattern of schizophrenic subjects
      deviates from that of depressed subjects in one behavior parameter; c) one
      specific behavior, talk-to-himself/herself, discriminates schizophrenic subjects
      from depressed and control subjects.

PMID- 10890348
TI  - Neuroanatomic differences among cognitive and symptom subtypes of schizophrenia.

PMID- 10890349
TI  - Medically self-harming behavior and its relationship to borderline personality
      among psychiatric inpatients.

PMID- 10890350
TI  - Borderline personality disorder exists in India.

PMID- 10890351
TI  - Microsporidia and Cyclospora: epidemiology and assessment of risk from the
      environment.
AB  - Two classes of parasites with an environmental stage in their lifestyle have
      recently emerged as significant gastrointestinal pathogens for humans.
      Microsporidia represent a group that contains a number of genera related to the
      genus Cryptosporidium. They are generally transmitted via direct human to human
      contact, but can survive in water and food, and recently have been found in
      surface water used as drinking source water. Their most common host range is in
      patients with clinical AIDS. Limited work to date suggests the group is
      susceptible to chlorine achievable CxT (concentration x time) values and is
      coagulated by filtration. Cyclospora cayetanensis is a species of parasite that
      has caused outbreaks from contaminated food. Its major risk is from the use of
      inadequately treated water used for irrigation. Cyclospora can infect normal and
      immunosuppressed hosts. Current information regarding the lifestyle,
      transmission, and control of both groups of parasites are discussed, with a
      health risk assessment analysis.

PMID- 10890352
TI  - Surface characteristics of Azospirillum brasilense in relation to cell
      aggregation and attachment to plant roots.
AB  - The free-living bacteria of the genus Azospirillum live in close association with
      plant roots and represent one of the best-characterized plant growth promoting
      rhizobacteria (PGPR). The attachment of Azospirillum to the roots is essential
      for the establishment of an efficient association with the host plant.
      Azospirillum cells are able to aggregate under certain environmental conditions,
      leading to the formation of bacterial flocs. The bacterial surface plays an
      important role in the establishment of the bacteria-plant association as well as
      in the bacterial aggregation and data suggesting the involvement of extracellular
      polysaccharides and proteins in these phenomena have been published. This review
      summarizes the current knowledge on the involvement of surface components in the
      adhesion processes of Azospirillum. Emphasis is placed on A. brasilense, the
      species that has been the subject of most studies in the Azospirillum genus.

PMID- 10890353
TI  - The natural evolutionary relationships among prokaryotes.
AB  - Two contrasting and very different proposals have been put forward to account for
      the evolutionary relationships among prokaryotes. The currently widely accepted
      three domain proposal by Woese et al. (Proc. Natl. Acad. Sci. USA (1990) 87: 4576
      4579) calls for the division of prokaryotes into two primary groups or domains,
      termed archaebacteria (Archaea) and eubacteria (Bacteria), both of which are
      suggested to have originated independently from a universal ancestor. However,
      this proposal, which is based primarily on genes involved in the information
      transfer processes, is inconsistent with the ultrastructural characteristics of
      prokaryotes as well as with many gene phylogenies and provides no explanation as
      to how the structural and molecular differences seen between these groups arose
      and how other prokaryotic taxa are related or evolved from the common ancestor.
      It also postulates that the last common ancestor of all organisms was a
      hypothetical entity lacking a cell membrane, which is contrary to the basic
      requirement of a cell membrane to define and separate all forms of life from the
      surrounding environment. A second alternate proposal for the evolutionary
      relationships among prokaryotes has emerged from extensive analyses of numerous
      conserved inserts and deletions found in various proteins (Gupta, R. S.,
      Microbiol. Mol. Biol. Rev. (1998)62: 1435-1491; FEMS Microbiol. Rev. (2000) 24:
      in press. This proposal points to a specific relationship between archaebacteria
      and gram-positive bacteria, both of which are prokaryotes bounded by a single
      cell membrane (monoderm prokaryotes). Gram-negative bacteria, which are bounded
      by two different membranes (diderm prokaryotes), are indicated to comprise a
      structurally and phylogenetically distinct taxa originating from gram-positive
      bacteria. This proposal postulates that the earliest prokaryote was a gram
      positive bacteria from which both archaebacteria and diderm prokaryotes evolved
      by normal evolutionary mechanisms in response to the strong selection pressure
      exerted by antibiotics produced by certain groups of gram-positive bacteria. This
      proposal accounts for both the molecular as well structural differences seen
      among the main groups of prokaryotes by known evolutionary mechanisms without
      invoking any hypothetical process or entity and thus is a closer representation
      of the natural relationships among prokaryotes than the proposal for two distinct
      domains. Based on this new proposal, it is now possible to logically deduce the
      branching order of different prokaryotic taxa from the common ancestor, which is
      as follows: Gram-positive bacteria (Low G + C) (<=> Archaebacteria) => Gram
      positive bacteria (High G + C) (<=> Archaebacteria)=> Deinococcus-Thermus =>
      Green nonsulfur bacteria => Cyanobacteria => Spirochetes => Chlamydia- Cytophaga
      Green sulfur bacteria => Proteobacteria-1 (epsilon, delta)=> Proteobacteria-2
      (alpha) => Proteobacteria-3 (beta) => Proteobacteria-4 (gamma). A surprising but
      very important aspect of the relationship deduced here is that the main
      eubacterial phyla are related to each other linearly rather than in a tree-like
      manner, suggesting that the major evolutionary changes within prokaryotes
      (bacteria) have occurred in a directional manner.

PMID- 10890354
TI  - Establishment of a CCR5-expressing T-lymphoblastoid cell line highly susceptible
      to R5 HIV type 1.
AB  - The beta-chemokine receptor CCR5 is considered to be an attractive target for
      inhibition of CCR5-using (R5 or macrophage-tropic) HIV-1. However, R5 HIV-1
      cannot replicate in CD4+ T cell or monocyte lines because of the lack of CCR5
      expression on their surface, which apparently hampers discovery and development
      of effective CCR5 antagonists against HIV-1 replication. In this study, we have
      established the CCR5-expressing T cell line MOLT-4/CCR5, highly permissive to the
      replication of R5 HIV-1. The cells express a considerable amount of CCR5 on their
      surface. When the cells were infected with the R5 HIV-1 strains Ba-L and JR-FL,
      the virus-induced cytopathic effect (syncytium formation) was observed, and the
      cells produced large amounts of HIV-1 p24 antigen in the culture supernatants.
      The analyses of progeny viruses for their coreceptor use and gp120 V3 nucleotide
      sequence revealed that they were R5 HIV-1. The parental cell line MOLT-4 was much
      less susceptible to Ba-L and totally insusceptible to JR-FL. Furthermore, MOLT
      4/CCR5 cells could support the replication of an R5 clinical isolate, but MOLT-4
      cells could not. When TAK-779, a novel small-molecule nonpeptide CCR5 antagonist,
      was examined for its inhibitory effect on R5 HIV-1 replication in MOLT-4/CCR5
      cells, the compound displayed potent antiviral activity, as demonstrated in
      peripheral blood mononuclear cells. These results indicate that the established
      cell line will be an extremely useful tool for experiments with R5 HIV-1.

PMID- 10890355
TI  - Prolonged infection of peripheral blood lymphocytes by Vif-negative HIV type 1
      induces resistance to productive HIV type 1 infection through soluble factors.
AB  - The auxiliary protein Vif is essential for productive HIV-1 infection of primary
      lymphocytes and macrophages. Vif is required for the synthesis of infectious
      progeny virus and infection of peripheral blood lymphocytes (PBLs) by Vif
      negative HIV-1 was thought to be confined to a single cycle. Here we define
      conditions for the maintenance of Vif-negative HIV-1 in PBLs during multiple
      rounds of viral infection. PBLs were infected with Vif-negative HIV-1 and then
      were serially cocultivated with uninfected PBLs. As determined by measurement of
      viral DNA, viral burdens declined but then rebounded and reached 1 copy per 30
      cells after 7 weeks of culture. Viral core antigen p24 levels dropped and
      remained below detection limits after three cocultivations with no observed
      cytotoxicity. Viral RNA was also undetectable in cocultivated cells. The
      incapacitating deletion in vif was maintained during cocultivation as shown by
      the size of the vif amplicon. The presence of viral DNA in the absence of viral
      p24 RNA or protein suggested that the cells were capable of control of HIV-1
      expression. This regulatory capacity was confirmed by the demonstration of
      resistance of PBLs or isolated CD4-positive cells to expression of exogenous wild
      type R5 or X4 HIV-1. Resistant PBLs were susceptible to fusion with HIV-1
      envelope-expressing cells and to reverse transcription of incoming viral DNA,
      indicating that the block to replication of exogenous virus was imposed after
      viral entry and DNA synthesis. Using a dual-chamber apparatus, we demonstrated
      that resistant Vif-negative HIV-1-infected PBLs secrete soluble factors that
      confer resistance on naive cells. These findings indicate that Vif-negative HIV-1
      infection of primary CD4-positive lymphocytes results in maintenance of
      unexpressed virus and induces the production of soluble factors conferring
      resistance to wild-type HIV-1 replication on uninfected cells.

PMID- 10890356
TI  - HIV disease progression and V3 serotypes in Brazil: is B different from B-Br?
AB  - HIV-1 serotype B-Br (GWGR) is rare in the United States but predominates in
      Brazil. Differences in prognosis for patients infected with serotype B-Br or
      serotype B (GPGR) have not been addressed previously. In this prospective cohort
      study, we compared the rate of disease progression between patients infected with
      the HIV-1 V3 serotype B or B-Br in Brazil. Progression to AIDS or death was
      studied by the Kaplan-Meier and Cox proportional hazard methods. Among 445 HIV
      infected patients who were tested with a specific enzyme immune assay, 204 (46%)
      had serotype B-Br infection and 127 (28%) had serotype B infection. Both groups
      were similar with regard to baseline CD4+ cell count, serum HIV RNA viral load,
      initial clinical stage, and the proportions who were treated with antiretroviral
      drugs. Patients with serotype B infection were significantly younger (p = 0.005)
      and tended to report homosexual behavior more frequently (p = 0.08). Mean follow
      up was 30 +/- 13.5 months. During the study period, 41 (32%) patients infected
      with serotype B and 44 (22%) infected with serotype B-Br developed AIDS (p =
      0.03). In a regression model adjusted for age and risk factor for HIV infection,
      progression to AIDS was faster in patients infected with serotype B (hazard ratio
      [HR] 1.59; 95% CI, 1.03-2.43; p = 0.03). A similar trend was observed in a model
      that considered AIDS or death as the outcome (HR, 1.43; 95% CI, 0.95-2.0; p =
      0.09). These results suggest that patients infected with closely related HIV-1
      serotypes may differ in the rate of progression to AIDS and indicate that
      serotype should be taken into account in HIV vaccine studies in Brazil.

PMID- 10890357
TI  - Relationship of CD4+ T cell counts and HIV type 1 viral loads in untreated,
      infected adolescents. Adolescent Medicine HIV/AIDS Research Network.
AB  - The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the
      Adolescent Medicine HIV/AIDS Research Network was designed as a study of an
      adolescent cohort composed of HIV-1-infected and -uninfected subjects. The goal
      of the analysis presented was to examine the relationship of CD4+ T cell counts
      and HIV-1 plasma viral loads in adolescents. The CD4+ T cell counts of 84 HIV+
      subjects who were 13 to 19 years of age were measured at the clinical sites,
      using ACTG standardized techniques. HIV-1 viral loads in frozen plasma were
      determined by the NASBA/NucliSens assay at a central laboratory. Past and current
      treatment with antiretroviral drugs was determined by medical record abstraction
      and interview data. The slope of the line generated by regressing log10 HIV-1 RNA
      (copies/ml) versus CD4+ T cell counts of REACH subjects who are antiretroviral
      drug naive was negative and significantly different than zero. A negative
      association has also been reported for antiretroviral drug-naive, adult males in
      the Pittsburgh Men's Study, a component of MACS (Pitt-MACS) (Mellors J, et al.:
      Science 1996;272:1167). These data show that in adolescents, as in adults, HIV-1
      RNA concentrations are correlated with corresponding absolute CD4+ T cell count.
      The slopes of the lines generated with data from each cohort were different (p =
      0.003). In addition to age, there are sex and racial differences in the makeup of
      the two cohorts. Any or all of these differences may affect the slopes of the
      lines.

PMID- 10890358
TI  - Tissue inhibitor of metalloproteinase 3, matrix metalloproteinase 9, and
      neopterin in the cerebrospinal fluid: preferential presence in HTLV type I
      infected neurologic patients versus healthy virus carriers.
AB  - The human retrovirus HTLV-I is responsible for the chronic progressive
      myelopathy, TSP/HAM, characterized by the presence of infiltrated T lymphocytes,
      cytokines, and matrix metalloproteinases (MMPs) within spinal cord lesions. MMPs
      have been associated with several neurological diseases, and we previously
      reported the specific presence of the extracellular matrix-degrading protease,
      MMP-9, in the cerebrospinal fluid of TSP/HAM patients. Nevertheless, previous
      studies have not yet shown whether the expression of MMP-9 is associated with
      HTLV-I infection per se, or with neurological symptoms following infection. In
      the present work, the presence of tissue inhibitors of metalloproteinases 1 and 3
      (TIMP-1 and TIMP-3) and of MMP-9 in the CSF of HTLV-I-infected individuals was
      compared in TSP/HAM patients versus HTLV-I carriers without neurological
      symptoms. TIMP-3, a regulator of MMP activity and cell survival, was detected
      with a significantly higher frequency in the TSP/HAM group and paralleled the
      increased levels of MMP-9 and neopterin, a sensitive indicator of cellular immune
      activation. These data may reflect the intense cell remodeling that occurs
      intrathecally in inflamed tissue. Changes in MMP, TIMP, and neopterin expression
      were not related to age at onset of disease, grade of motor disability,
      progressor status, or duration of disease, presumably indicating that TSP/HAM
      patients are continuously subjected to viral and immunological pressure. All
      these observations suggest that TIMPs and MMPs may contribute to the pathogenesis
      of TSP/HAM, and hence a new therapeutic strategy targeting the MMP/TIMP balance
      is needed. These observations also suggest that MMP-9 and TIMP-3 in CSF may be
      useful markers in the follow-up of the efficacy of therapeutic trials in TSP/HAM
      patients.

PMID- 10890359
TI  - HIV type 1 envelope subtype C sequences from recent seroconverters in Zimbabwe.
AB  - HIV-1 envelope sequence patterns have implications for virus cell tropism and for
      the development of an effective vaccine. To identify the sequence characteristics
      of recently transmitted HIV-1 isolates in southern Africa, we sequenced the V3-V5
      envelope regions of 24 male seroconverters in Harare, Zimbabwe. Each of the
      sequences clustered with previously reported subtype C isolates and there was a
      mean 17% intersequence pairwise genetic distance between the Zimbabwean isolates.
      Three isolates were syncytium inducing (SI). One of the SI isolates had an
      unusual GIGK crown and a deletion at codon 23; one had the codon 23 deletion
      alone; and one had a high net positive charge in the V3 loop. The extensive
      genetic diversity within the envelope of subtype C HIV-1 isolates must be
      considered in vaccine development. Further analysis of subtype C SI isolates and
      site-directed mutagenesis experiments are required to determine the molecular
      basis of SI activity in global HIV-1 isolates.

PMID- 10890360
TI  - Generation and structural analysis of soluble oligomeric gp140 envelope proteins
      derived from neutralization-resistant and neutralization-susceptible primary HIV
      type 1 isolates.
AB  - We generated DNA constructs expressing soluble truncated forms of the envelope of
      SF162, a neutralization-resistant primary human immunodeficiency virus type 1
      isolate, and SF162AV2, a neutralization-susceptible virus derived from SF162
      after the deletion of 30 amino acids from the V2 loop. The constructs express the
      entire gp120 subunit and the extracellular region of the gp41 subunit, with
      either the presence ("cleaved" forms, designated gp140C) or the absence ("fused"
      forms, designated gp140F) of the gp120-gp41 cleavage site. Both gp140 forms
      derived from SF162 and SF162deltaV2 are secreted in the cell medium and are
      recognized by the oligomer-specific anti-gp41 MAb T4. As is the case for the
      corresponding virion-associated envelope molecules, the CD4-binding region is
      occluded within both gp140F and gp140C forms. However, structural differences
      exist between these two forms. The gp140F proteins are less efficiently
      recognized than the gp140C proteins by antibodies present in the sera of HIV
      infected patients with neutralizing activities against SF162 and SF162AV2. Also,
      the V3 loop is more exposed on gp140F than gp140C. As is the case for intact
      virions, on CD4 binding both the gp140F and gp140C proteins undergo
      conformational changes that result in the exposure of the epitope recognized by
      MAb 17b, which has been implicated in coreceptor binding. In contrast, during
      these structural changes the exposure of specific V3 loop epitopes is not
      increased on either gp140C or gp140F. Taken together, our data indicate that
      although these gp140 forms differ structurally from the native envelope, their
      similarities, in particular that of gp140C, outweigh their differences.

PMID- 10890361
TI  - Identification and characterization of differentially expressed mRNAs in HIV type
      1-infected human T cells.
AB  - We used a novel differential display (DD) technique to identify host factors
      involved in virus replication, pathogenesis, and host response in HIV-1-infected
      T cells. Thirteen cDNA fragments differentially expressed in HIV-1NL4-3-infected
      MT-4 cells prior to the occurrence of specific apoptotic cell death were
      sequenced and identified. Two of seven elevated genes were identical to HIV-1
      sequences and the other five were MIP-1alpha, ACTE-III, CD11c, arginase I, and
      CCR5. The six downregulated genes included prothymosin-a, Jaw-1, proteasome
      subunit XAPC7, splicing factor 9G8, GA17 protein, and an unknown mRNA. Northern
      blot and RT-PCR analyses confirmed the altered gene expressions in MT-4 cells as
      well as in another T cell line, MOLT-4. We also revealed that the amount of MIP
      1alpha in culture supernatant of HIV-1-infected cells was increased by more than
      15-fold relative to control cells, and the expression of its receptor CCR5 was
      cooperatively upregulated on the surface of these cells. Furthermore, the
      upregulation of CD11c after HIV-1 infection was slightly inhibited by blocking
      the MIP-1alpha-mediated signal transduction. These results indicate that genes
      altered on HIV-1 infection may be mutually organized and play an important role
      in HIV-1-induced pathogenesis.

PMID- 10890362
TI  - Evidence of a high frequency of HIV-1 subtype F infections in a heterosexual
      population in Buenos Aires, Argentina.
AB  - We analyzed HIV-1 genetic variability, phylogenetic relationships, and
      association with transmission modes among 58 HIV-1-infected patients from Buenos
      Aires City, Argentina. The 58 strains were classified as env(gp41) HIV-1 group M
      subtype B (n = 34) and subgroup F1 of subtype F (n = 24). Potential recombinants
      combining parts of viral regions from different subtypes, B(prot)/F(env) and
      F(prot)/B(env), were found in two patients, and a dual infection with HIV-1 prot
      subtypes B and F was identified in one individual. Epidemiologic analysis of
      behavioral risks revealed that the frequency of infection with subtype F viruses
      was significantly higher (p < 0.0001) among heterosexual patients (71%) compared
      with homosexual patients (11%). The spread of non-B subtypes into heterosexual
      populations may be more common than previously thought. Our findings provide
      important information for monitoring the transmission of HIV-1 strains among
      different risk groups in Argentina as well as for vaccine development.

PMID- 10890363
TI  - HIV type 1 A/J recombinant with a pronounced pol gene mosaicism.
AB  - A nearly full-length genome sequence of a novel HIV-1 A/J recombinant with a
      complex structure of the pol gene has been analyzed. This virus was isolated in
      1998 from a 35-year-old female from Botswana. The virus demonstrated a dual
      pattern for CXCR4/CCR5 coreceptor utilization. Using short-term enrichment of the
      donor's PBMCs, the 98BW21 isolate was long-range amplified, cloned, and
      sequenced. The sequence of the clone 98BW21.17 spanned 9103 bp from the PBS site
      to the U5 region of the 3' LTR. The phylogenetic relationship of the 98BW21.17
      clone to HIV-1 sequences represented by M, N, and O groups and A-K subtypes of
      the M group was examined across the entire viral genome. The 98BW21.17 clone
      demonstrated a unique phylogenetic topology clustering within subtype A or
      subtype J reference sequences. However, the subtype origin of two regions within
      the pol gene (p51 RT and integrase) could not be identified. Recombination
      patterns of the 98BW21.17 clone were different from known AGJ/AGIJ-type viruses
      such as isolates BFP90 and 95ML84. This study demonstrated the existence and
      replication competence of a new dual-tropic X4/R5 recombinant form of HIV-1 on
      the subtype J backbone. The nucleotide sequence of the 98BW21.17 clone was
      submitted to GenBank under accession number AF192135.

PMID- 10890364
TI  - Computer based generation of reaction mechanisms for gas-phase oxidation
AB  - This paper describes EXGAS, an advanced software for the automatic generation of
      reaction mechanisms. It has been developed to model the gas-phase oxidation of
      some components of gasoline, alkanes and ethers. The chemistry involved in these
      validated mechanisms relies both on a reaction base for some particular species
      and for the largest part on generic elementary reactions, which are well known
      for the oxidation of hydrocarbons. The programming of this system is mainly based
      on a referenced canonical treelike description of molecules and free radicals and
      can handle both acyclic and cyclic compounds. Mechanisms are generated in a way
      to ensure their comprehensiveness. Chemical models, which can directly be used by
      codes of simulations, are obtained as a result.

PMID- 10890365
TI  - Step by step filter based program for calculations of highly informative
      derivative curves
AB  - We have developed a microcomputer program, based on a recently described approach
      called step by step filter (SBSF), for calculation of derivative curves directly
      from spectra recorded as a function of wavelength. This program avoids the long
      wavelength attenuation featured at conventional method for derivative curves
      calculation, and in this extent could be very helpful for daily spectroscopy
      practice. The features of the SBSF program include: easy treatment of data
      through a windowed environment, calculating of both conventional and step by step
      filter derivatives, possibilities for selection of the mathematical conditions
      for smoothing and differentiation simultaneous plotting of the original curve and
      its derivative and a mouse pointer. Several examples from different branches of
      the molecular spectroscopy (absorption UV-VIS, CD and fluorescence) are provided
      and discussed in the terms of advantages of SBSF.

PMID- 10890366
TI  - Maximum topological distances based indices as molecular descriptors for QSPR: 2-
      application to aromatic hydrocarbons
AB  - Several standard topological indices based upon two different distance matrix
      definitions are employed to analyse their use to predict normal boiling points of
      a representative set of aromatic hydrocarbons. Results are quite satisfactory and
      they reveal the suitability of resorting to the maximum distance concept to
      compute the molecular indices, being in complete agreement with our previous
      findings on this issue.

PMID- 10890367
TI  - A generalization of Numerov's method for the numerical solution of the
      Schrodinger equation in two dimensions
AB  - In this paper generalizations of the well known Numerov's method are obtained.
      The local truncation errors of the new methods are presented and the result of
      the application of the new methods to a two-dimensional Schrodinger equation in
      an equal space discretization is presented. Numerical illustrations show the
      efficiency of the new methods compared with the known five-point formula in two
      coulombic potentials.

PMID- 10890368
TI  - Dehydrogenation processes and molecular clusters in mass spectra of
      organometallic and coordination compounds
AB  - A method for the calculation of components from the complex molecular pattern is
      proposed. The modelling of molecular ion region in mass spectrum is applied to
      cases where for detection of the dehydrogenation processes effects such as losses
      of protons, hydrogen radicals or hydrogen molecules may occur. The parts of (M-H)
      and (M-2H) bands are determined as components of the picture observed in the
      molecular ion range of mass spectrum. Positive results of the modelling show, the
      hydrogen losses should be considered in resulted spectrum interpretation. The
      components contributions were computed by the least squares method, in which
      optimisation is based on Hooke Jeeves procedure. Such an approach resulted in
      model fits within 1% precision for the cluster containing five or more peaks.
      Applications of the method are presented for 2-methyl-selenolo[2.3-b]-pyridine
      C8H7NSe, ethyl-digermane C2H10Ge2 and methyl-mercuric-dicyandiamide C3H10HgN4.

PMID- 10890369
TI  - On extensions of approaches for heat recovery calculations in integrated chemical
      process systems
AB  - This paper deals with heat recovery calculations in integrated chemical process
      systems. A level of heat recovery in a heat exchanger network (HEN) determines
      the cost of heat energy consumed in a total system and influences environmental
      pollution. Even though well established approaches to the problem of calculating
      minimum cost of utilities in a HEN are available at present, they do not fully
      account for complex industrial scenarios. The aim of methods developed in this
      work is to extend applications for the following cases: 1. multiple utilities of
      great temperature spans (so called non-point utilities), and 2. disturbances of
      flow-rates of heat exchanging streams. To solve the problems, methods have been
      developed based on optimisation models. The models are linear though one of them
      involves mixed-integer variables. Linearity ensures the possibility of solving
      the models to global optimum, even for large-scale industrial problems. The
      description of solution methods and examples of applications are presented in
      this paper.

PMID- 10890370
TI  - Structure refinement of quaternary spinel oxides experiments and modelling
AB  - Comprehensive studies have been undertaken, inclusive of experimental and
      computational techniques, on the structure and cation distribution of spinel
      solid solutions formed between the normal spinel LiMn2O4 and inverse LiFe5O8.
      Series of solid solutions of a composition (1 - x)LiMn2O4 x xLi0.5Fe2.5O4 are
      single phase products with spinel structure in the whole range of x, displaying a
      cubic structure. With increasing Fe3+ content, the tendency of ordering by
      lithium ions in octahedral spinel sites and a strongly marked preference of Li+
      cations to occupy the octahedral positions is apparent. Modelling and refinement
      of crystal structure of such spinel solid solution series have been undertaken by
      the energy minimisation procedure, together with the interatomic potentials
      calculation, explaining some divergences of the experimental data.

PMID- 10890371
TI  - Relationship of crystal structure to interionic interactions in the lithium
      manganese spinel oxides
AB  - Lithium manganese oxides in the form of cubic spinel phases (space group Fd3m)
      are formed in a LixMn3-xO4 system for rather limited values of x. Structural
      investigations by X-ray powder diffraction, applied to the Li-Mn-O compounds,
      indicate the formation of a second crystalline phase, Li2MnO3 (space group C2/m),
      with the increasing lithium content. Total Li+ content per unit cell and the
      cation distribution over a spinel lattice in LixMn3-xO4 have been studied by
      measurements of integrated intensities of X-ray reflections, and by structure
      refinement using Rietveld profile analysis. In an attempt to understand the
      factors affecting cation distribution in the spinel lattice, we applied the
      computer modelling techniques and investigated the Li+, Mn3+ and Mn4+ ion
      distribution by calculating the lattice energy, combined with energy minimisation
      procedures, using the General Utility Lattice Program (GULP), a program designed
      for simulation of ionic and semi-ionic solids, based on interatomic potential
      models.

PMID- 10890372
TI  - The comparative molecular surface analysis (COMSA): a novel tool for molecular
      design.
AB  - A new method allowing for 3-D QSAR analysis and the prediction of biological
      activity is presented. Unlike comparative molecular field analysis (CoMFA)-like
      techniques, it is based not on a comparison of the properties characterizing a
      discrete set of points but on the mean electrostatic potential (MEP) calculated
      and labeling specific areas defined on the molecular surface. A Kohonen self
      organizing neural network and partial least square (PLS) analysis have been used
      for performing such an operation. The series of steroids complexing the
      corticosteroid (CBG) and testosterone (TBG) globulins, which forms a benchmark
      measuring the performance of the methods in molecular design, and a series of
      benzoic acids described by the Hammett sigma constants is used for testing the
      method. It is demonstrated that a method can be used efficiently to evaluate the
      responses determined both by the combination of electrostatic and steric effects
      or by electrostatic effects alone, therefore, two different schemes were
      developed. The first one, which involves PLS analysis of the full comparative
      networks, covers both steric and electrostatic effects. This scheme works well
      for both the CBG and TBG data. The second scheme takes into account only the
      properties (MEP) of these regions within molecules that can be superimposed with
      the template molecule. This scheme provides the best predictive power for the
      benzoic acids series. Comparison of the results from a CoMFA analysis proves that
      method is at least as effective for the responses limited by electrostatic
      effects, although it significantly outperforms CoMFA for CBG affinity which is
      dominated by steric effects.

PMID- 10890373
TI  - Animal models of uveal melanoma.
AB  - Many attempts have been made to develop a suitable animal model to study more
      effectively the aetiology, pathogenesis, diagnosis and therapy of intraocular
      (uveal) melanoma. Uveal melanoma may spontaneously occur in some animals,
      including dogs, cats, horses, rats, mice, birds and fish. The histological
      features, metastatic behaviour and unpredictable nature of occurrence of these
      uncommon spontaneous tumours detract from their suitability as a model. Several
      methods have been developed to induce intraocular melanoma chemically or by
      radiation in laboratory animals. Some of these induced tumours resemble human
      uveal melanoma, although the majority originate from the retinal pigment
      epithelium. Uveal proliferations have been biologically induced by feline
      leukaemia/sarcoma virus and simian virus 40, although the presence of virus in
      tumour cells and extraocular tumours resulting from shed virus detract from the
      utility of this model. Inoculation of tissue culture hamster, murine or human
      melanoma cells into animal eyes has the advantage that the inoculation site and
      size of inoculum can be controlled. Disadvantages include the immune suppression
      necessary for tumour growth in some models as well as the fact that many of the
      melanoma cell lines are of cutaneous origin. Transgenic murine models have been
      developed using the promoter region of the tyrosinase gene to target expression
      of oncogenes in melanin-producing cells. Spontaneous intraocular pigmented
      tumours and distant metastases may occur, although many, if not all, of the
      intraocular tumours arise in the retinal pigment epithelium.

PMID- 10890374
TI  - Quantitative analysis of tyrosinase and tyrosinase-related protein-2 mRNA from
      melanoma cells in blood by real-time polymerase chain reaction.
AB  - Several studies have evaluated the use of polymerase chain reaction (PCR)
      amplification of tyrosinase mRNA to detect melanoma cells in blood. However,
      contradictory results have been obtained from different groups. We therefore have
      developed and validated a quantitative PCR method for tyrosinase and tyrosinase
      related protein-2 (TRP-2) mRNA. An important methodological finding was that high
      concentrations of reverse transcriptase or RNA sample inhibited the following
      PCR. This could be abolished by dilution of the cDNA sample before the PCR.
      Standard curves with a linear range over at least five logs were obtained with
      dilutions of melanoma cell cDNA. Controls (RNA and cDNA) consisting of melanoma
      cells (1000/ml) added to blood were analysed repeatedly over 3 months, resulting
      in means between 880 and 1074 AU/ml. The RNA controls were stable, whereas the
      cDNA controls, as well as the calibrators, showed a tendency to change over time.
      The variation in the RNA controls was 25% for tyrosinase and 22% for TRP-2. Seven
      stage III-IV melanoma patients were tested for tyrosinase and TRP-2 transcripts
      in blood drawn from a peripheral vein and from a Port-a-cath. Tyrosinase mRNA was
      found in three patients (0.8-12.4 AU/ml). For TRP-2, the same amount was found in
      the patients as in healthy donors. No differences were seen between blood from a
      peripheral vein and from the Port-a-cath. We here present fast and sensitive
      methods for the quantification of tyrosinase and TRP-2 mRNA in blood.

PMID- 10890375
TI  - Sequential chemoimmunotherapy with cisplatin, interferon-beta and interleukin-2
      inhibits the growth of B16-F1 melanoma in syngeneic mice.
AB  - Sequential combinations of chemotherapy with biological response modifiers has
      recently been evaluated as systemic treatment for patients with advanced
      melanoma. The response rates of the chemoimmunotherapy were reported to be higher
      than conventional treatment using chemotherapy or biological agents alone. To
      investigate the effectiveness of such chemoimmunotherapy, we evaluated the
      antitumour effect of sequential chemoimmunotherapy in vivo using a B16 mouse
      melanoma system. In this sequential regimen, administration of cisplatin (CDDP)
      was followed by interferon-beta (IFNbeta) and interleukin-2 (IL-2). This
      combination therapy synergistically inhibited the growth of B16-F1 melanoma and
      prolonged the survival of mice bearing B16-F1. In contrast, this therapy did not
      show any antitumour effect on B16-F10 melanoma. The exact mechanism of the
      antitumour effect is not clear, but the following results were noted: no
      synergistic effect of this therapy was detected in nude mice, neutralizing anti
      IFNgamma antibody significantly blocked the antitumour effect of this therapy,
      and the number of apoptotic melanoma cells was significantly increased in
      melanoma tissues removed from mice treated with this therapy. These results
      demonstrated the potent immunological antitumour effect of this sequential
      chemoimmunotherapy.

PMID- 10890376
TI  - Large deletions of chromosome 9p in cutaneous malignant melanoma identify
      patients with a high risk of developing metastases. Hospital Clinic Malignant
      Melanoma Group, University of Barcelona.
AB  - Cutaneous malignant melanoma (CMM) is an aggressive tumour with a high metastatic
      potential. Deletions of chromosome 9p have been detected in CMM, some of which
      involve the CDKN2A/p14ARF genes. Loss of heterozygosity (LOH) of 16
      microsatellite markers on 9p and mutations in the CDKN2A/p14ARF genes had been
      previously studied in 32 melanoma patients by our group. 9p deletions were
      detected in 15 primary tumours (45.5%) and are here correlated with the clinical
      outcome over 5 years and compared with classical prognostic factors. Eight of the
      32 patients developed metastases (25%). The metastases were all detected within
      768 days of the initial diagnosis. The patients without metastases were last
      monitored at least 1621 days after diagnosis. None of the 21 patients with more
      than eight microsatellites conserved developed metastases, whereas all of the
      eight patients who developed metastases had eight or more markers deleted. The
      sensitivity of this analysis to predict metastases was 100% (specificity 84%),
      whereas the sensitivity for the same sample using a Breslow thickness > 3 mm was
      62.5% (specificity 68%). LOH of eight or more of the 9p microsatellite markers is
      therefore a useful prognostic factor to predict the development of metastases in
      the first 4.4-6.3 years (1621-2294 days).

PMID- 10890377
TI  - The value of serum S-100beta and interleukins as tumour markers in advanced
      melanoma.
AB  - Recently serum S-100beta has shown promise as a tumour marker in melanoma;
      however, its use as a prognostic marker in the advanced stage needs to be
      confirmed. Interleukins (ILs) may mediate regression or progression of cancer. In
      order to study their relation to the metastatic profile and survival, we
      evaluated the association between pretreatment serum levels of S-100beta, IL-6,
      IL-10 and IL-12 and metastatic site and survival in 50 patients with advanced
      melanoma who were to receive chemoimmunotherapy. Patients with liver and/or bone
      metastases had significantly higher median concentrations of S-100beta, IL-6 and
      IL-10 than those with only skin, nodal and/or lung involvement. The differences
      in IL-12 levels were unremarkable. Using univariate analysis, the S-100beta level
      and metastatic profile were found to be statistically significant prognostic
      factors for survival. Using multivariate analysis the S-100beta level was the
      most powerful prognostic indicator, while the metastatic profile was found to be
      significant after exclusion of S-100beta. The findings suggest that elevated
      serum levels of S-100beta, IL-6 and IL-10 reflect concurrent liver or bone
      metastases in melanoma. S-100beta is also an independent prognostic marker.
      Pretreatment IL levels were not associated with outcome.

PMID- 10890378
TI  - Prognostic value of beta1 integrin expression in metastatic melanoma.
AB  - The expression of integrin-type cell adhesion receptors is frequently changed in
      malignant transformation. Despite their important role in cancer cell behaviour,
      the value of integrins as prognostic markers is mostly unknown. We have examined
      the expression of beta1 integrins in 38 metastatic melanomas obtained from 27
      patients treated with combined chemoimmunotherapy. On the basis of beta1 integrin
      expression, the melanoma samples were divided into two groups: beta1-negative
      tumours (<10% beta1 integrin immunostained cells) and beta1-positive tumours
      (with > or = 10% positive cells). Patients with beta1-positive tumours (n = 15)
      had significantly longer disease-free survival (median 38 versus 7 months, P <
      0.0001) and overall survival (median 70 versus 23 months, P = 0.0001) evaluated
      after the diagnosis of primary disease compared with patients with beta1-negative
      metastases (n = 11). Moreover, the survival of the patients with beta1-positive
      tumours after the initiation of chemoimmunotherapy was significantly prolonged
      (median 18 versus 9 months, P = 0.017). The independent nature of beta1 integrin
      expression as a significant prognostic factor for survival after therapy was
      confirmed using Cox's multivariate analysis (P = 0.014). Our results indicate
      that the expression of beta1 integrins might have some major tumour growth
      regulatory role and can be used as a predictor for prognosis in patients with
      metastatic melanoma.

PMID- 10890380
TI  - MAGE-12 and MAGE-6 are frequently expressed in malignant melanoma.
AB  - MAGE proteins have been identified as potential specific targets for cancer
      vaccination. Although MAGE-6 and MAGE-12 were originally identified in malignant
      melanoma there are no studies reporting the frequency of expression of these
      antigens in this malignancy. These are of relevance particularly for MAGE-6 as
      recent studies have identified CTL activity against several epitopes. We have
      studied MAGE-1, -2, -3, -4, -6 and -12 gene expression using reverse
      transcription-polymerase chain reaction in 47 melanoma samples and 11 melanoma
      cell lines established from these tumours. The tumour samples expressed MAGE-12
      (74%) and MAGE-6 (64%) mRNA at much higher frequencies than the other MAGE genes.
      MAGE-12 and MAGE-6 were expressed at the highest frequencies, relative to the
      other MAGE antigens, in early stage lesions. The frequency of expression of all
      the MAGE genes was found to be higher in samples from metastatic deposits
      compared to those from locoregional disease. The cell lines all expressed the
      same or more MAGE antigens than the tumours from which they were derived. In only
      one cell line was expression of a MAGE antigen lost. Certain recurring patterns
      of MAGE expression were observed in the tumour samples. MAGE-6 and/or -12
      expression were detected in all of those 26 tumour samples that were positive for
      one or more of MAGE-1, -2, -3 and -4. Twenty of these 26 samples expressed both
      antigens. These findings suggest that protocols targeting MAGE-12 and -6 would
      permit many more patients to be included into clinical cancer vaccination trials.

PMID- 10890379
TI  - Serum values of tumour necrosis factor-alpha and of soluble tumour necrosis
      factor-R55 in melanoma patients.
AB  - Tumour necrosis factor-alpha (TNFalpha) is a cytokine with a variety of
      biological activities, including an effect on tumour growth. The soluble TNF
      receptor TNF-R55 (sTNF-R55) inhibits TNFalpha functioning. Serum values of
      TNFalpha and TNF-R55 have been observed in patients with different cancers. To
      determine the serum values of TNFalpha and its soluble receptors and to
      investigate the prognostic value of sTNF-R55, we studied the sera of 68 patients
      with metastatic melanoma, 109 patients with no recurrent disease after surgical
      removal of melanoma, and 69 healthy controls. At least four different monoclonal
      antibodies against human TNFalpha and human TNF-R55, respectively, were prepared
      to obtain sensitive and reliable sandwich enzyme-linked immunosorbent assays. We
      found that in patients with metastatic melanoma the serum values of sTNF-R55 were
      significantly higher (2.41 ng/ml; range 0.02 23.0 ng/ml; P < 0.05) than in the
      melanoma patients without recurrence (0.54 ng/ml; range 0.02-6.25 ng/ml) and
      healthy controls (0.5 ng/ml; range 0.02 5.0 ng/ml). The sTNF-R55 concentrations
      increased as the disease progressed. Patients with metastatic melanoma also had
      significantly higher concentrations of TNFalpha (3.34 ng/ml; range 0.03-30.0
      ng/ml; P<0.05) than patients without recurrence (1.24 ng/ml; range 0.02 23.0
      ng/ml). Patients with metastatic melanoma, a high sTNF-R55 concentration, a low
      TNFalpha concentration and a low TNF:sTNF-R55 ratio had the worst prognosis. Low
      values of sTNF-R55 (<0.6 ng/ml) were associated with favourable response to
      chemotherapy (P = 0.007). According to our findings, patients with metastatic
      melanoma have higher values of sTNF-R55 than the controls and melanoma patients
      without recurrence. sTNF-R55 values higher than 0.6 ng/ml and a TNF:sTNF-R55
      ratio lower than 1.5 are unfavourable prognostic factors for response to
      chemotherapy.

PMID- 10890381
TI  - Improving screening for melanoma by measuring similarity to pre-classified
      images.
AB  - A new method that can dramatically improve the sensitivity and especially the
      specificity of skin naevi screening for melanoma by physicians is introduced. The
      method is based on measuring the similarity to previously classified naevi
      images. As more naevi are being classified, the power of the method is enhanced.
      Thus physicians can benefit from experience accumulated by others and the
      screening can be performed effectively by physicians with less experience.

PMID- 10890382
TI  - Epiluminescence microscopy features of cutaneous malignant melanoma metastases.
AB  - Especially small and/or initial cutaneous malignant melanoma metastases (CMMMs)
      are tumours with inconspicuous clinical and sometimes histological features which
      may be difficult to differentiate from benign melanocytic lesions or angiomas.
      Thus it would be very valuable to have additional criteria for the differential
      diagnosis of such lesions. Thirty histologically verified CMMMs were examined
      using epiluminescence microscopy (ELM) in order to visualize a large number of
      morphological features permitting the recognition of malignancy. One hundred
      primary cutaneous malignant melanomas (PCMMs), 50 dysplastic naevi, 50 common
      naevi, 30 blue naevi and 20 haemangiomas served as the control group; these were
      randomly selected from a large data base and were all reviewed for histological
      diagnosis. Four of the 24 features studied were shown to differ significantly
      between CMMMs and the control group. Two features of the malignant tumour group
      (CMMM and PCMM) differed significantly from the benign tumour group. A
      polymorphic angiectatic base pattern and/or vascular aneurysms, peripheral
      erythema, brown-grey coloration as a negative criterion (i.e. its absence is
      indicative of CMMM) and a light brown halo had a specificity of 86.7-96.0% for
      CMMM. Areas of polymorphic and/or horizontally dilated capillaries and a saccular
      pattern had a specificity of 97.3-99.2% for the malignant group (CMMM and PCMM).
      Three features - peripheral greyish patches, lesions surrounded by grey streaks
      (melanoma cell infarcts of the vessels) and microscopic ovoid blood lakes
      (spontaneous microhaemorrhages)--were absent in the benign group. The prevalence
      of distinct ELM criteria in CMMM represents a useful enhancement for the
      diagnosis of malignancy in melanocytic skin lesions.

PMID- 10890383
TI  - Radioimmunoconjugates for targeted alpha therapy of malignant melanoma.
AB  - Effective targeted cancer therapy requires high selectivity and cytotoxicity. To
      this end we have prepared and tested a new alpha-emitting radioimmunoconjugate
      (RIC) against malignant melanoma. The melanoma antibody 9.2.27 is specific for
      most melanoma cell lines. This antibody was labelled with an a emitter, bismuth
      213 (213Bi), and a positron emitter, terbium-152 (152Tb), which is an analogue of
      the alpha-emitting radioisotope terbium-149. The chelators cDTPAa (a cyclic
      anhydride of diethylenetriamine pentacetic acid) and CHX-A" (a 2-(p-SCN-Bz)
      cyclohexyl-DTPA ligand) were used in order to obtain high labelling yields for
      both isotopes with either chelator. The labelling efficiency with 213Bi was found
      to be 96% and 92% with cDTPAa and CHX-A", respectively. With 152Tb it was 93% and
      89%, respectively. Serum stability studies showed 20% leaching with 213Bi over a
      period of 2.5 half-lives. For 152Tb the leaching was 13%. There was no difference
      in the melanoma cell binding of the labelled and unlabelled antibodies. DNA
      synthesis data were compared for both isotopes with either chelator. Based on
      these results, the therapeutic activity ratio for 213Bi a particles and 152Tb
      positrons for the same endpoint was calculated to be 120. The stability of the
      bismuth and terbium RICs, together with the outstanding cytotoxicity of the alpha
      emitter, provides the basis for a new approach to the potential control of
      micrometastatic melanoma.

PMID- 10890384
TI  - Interleukin-2 plus chemotherapy for patients with metastatic melanoma.
AB  - We studied the activity of recombinant interleukin-2 (IL2) in combination with
      multiagent chemotherapy in the treatment of patients with disseminated malignant
      melanoma. Patients were randomized to receive the same dose of lymphokine by
      constant 24 h intravenous infusion (CI) or by subcutaneous bolus (SB) injection.
      Twenty-two patients, 18 males and four females with a median age of 44 years
      (range 32-73 years) were randomized to receive IL2 5 million units/m2 once daily
      by SB injection or by CI, 5 days/week for 2 weeks. All patients received a
      chemotherapy regimen consisting of lomustine (CCNU) 75 mg/m2 on day 14, bleomycin
      10 units/day by CI for 5 days (days 14-19) and cisplatin 75 mg/m2 on day 19.
      Patients were retreated after a 3 week interval. There were four complete
      responses and one partial response in the CI arm and two partial responses in the
      SB arm. The median duration of response was 38 weeks (range 26-107 weeks). The
      median duration of survival was 6.7 months in non-responders and 11.1 months in
      responders. The overall response rate was 32%. Since responses were brief and all
      the responding patients progressed after a median of 38 weeks, the study was
      terminated before accrual goals were met.

PMID- 10890385
TI  - Selective uptake of para-boronophenylalanine increases in amelanotic melanoma
      cells transfected by the tyrosinase gene.
AB  - To investigate the mechanism of uptake of para-boronophenylalanine (p-BPA), a
      capture agent for boron neutron capture therapy (BNCT) of melanoma and brain
      tumour, into melanoma cells, we studied the relationship between melanin
      synthesis and the concentration of boron using tyrosinase-deficient mouse
      amelanotic melanoma cells (A1059) and melanotic melanoma cells (TA1059). A1059
      was established from mouse B16F10 cells, and TA1059 was constructed by
      transfecting human tyrosinase cDNA into A1059. The melanin content of TA1059 was
      1.5-fold higher than that of B16F10, and was undetectable in A1059. The order of
      p-BPA uptake was TA1059 > B16F10 > A1059 at the time points examined, and the
      boron content of TA1059 was approximately 1.5-fold higher than that of B16F10.
      Our experimental findings indicated that melanin synthesis is a very important
      factor for characterizing the increase in accumulation of p-BPA in melanoma
      cells. A significant difference in boron uptake into TA1059 was observed between
      p-BPA and meta-BPA (m-BPA), but there were no apparent differences in the case of
      A1059. The difference in accumulation of p-BPA and m-BPA could be due to
      differences in the properties of p-BPA as a tyrosine analogue needed for melanin
      synthesis.

PMID- 10890386
TI  - Probabilistic and statistical properties of words: an overview.
AB  - In the following, an overview is given on statistical and probabilistic
      properties of words, as occurring in the analysis of biological sequences. Counts
      of occurrence, counts of clumps, and renewal counts are distinguished, and exact
      distributions as well as normal approximations, Poisson process approximations,
      and compound Poisson approximations are derived. Here, a sequence is modelled as
      a stationary ergodic Markov chain; a test for determining the appropriate order
      of the Markov chain is described. The convergence results take the error made by
      estimating the Markovian transition probabilities into account. The main tools
      involved are moment generating functions, martingales, Stein's method, and the
      Chen-Stein method. Similar results are given for occurrences of multiple
      patterns, and, as an example, the problem of unique recoverability of a sequence
      from SBH chip data is discussed. Special emphasis lies on disentangling the
      complicated dependence structure between word occurrences, due to self-overlap as
      well as due to overlap between words. The results can be used to derive
      approximate, and conservative, confidence intervals for tests.

PMID- 10890387
TI  - The effect of nonhomogeneous clone length distribution on the progress of an STS
      mapping project.
AB  - We provide both theoretical and simulation results on the progress of an STS
      mapping project in the presence of clone length inhomogeneity. For an example in
      which the genome comprises alternating regions of clones with short and long
      average length, the main conclusion is that the efficiency of the project is
      clearly decreased in the presence of such inhomogeneity. The case of
      deterministic clone length gives the worst progress. The general simulation
      algorithm we propose shows that strategies that space the anchors as regularly as
      possible do best: fewer contigs of larger average length are expected. The
      simulation algorithm can be used to study many statistical properties of the
      progress of any anchoring project.

PMID- 10890388
TI  - Ligand-receptor pairing via tree comparison.
AB  - This paper introduces a novel class of tree comparison problems strongly
      motivated by an important and cost intensive step in drug discovery pipeline
      viz., mapping cell bound receptors to the ligands they bind to and vice versa.
      Tree comparison studies motivated by problems such as virus-host tree comparison,
      gene-species tree comparison and consensus tree problem have been reported. None
      of these studies are applicable in our context because in all these problems,
      there is a well-defined mapping of the nodes the trees are built on across the
      set of trees being compared. A new class of tree comparison problems arises in
      cases where finding the correspondence among the nodes of the trees being
      compared is itself the problem. The problem arises while trying to find the
      interclass correspondence between the members of a pair of coevolving classes,
      e.g., cell bound receptors and their ligands. Given the evolution of the two
      classes, the combinatorial problem is to find a mapping among the leaves of the
      two trees that optimizes a given cost function. In this work we formulate various
      combinatorial optimization problems motivated by the aforementioned biological
      problem for the first time. We present hardness results, give an efficient
      algorithm for a restriction of the problem and demonstrate its applicability.

PMID- 10890389
TI  - Efficient detection of unusual words.
AB  - Words that are, by some measure, over- or underrepresented in the context of
      larger sequences have been variously implicated in biological functions and
      mechanisms. In most approaches to such anomaly detections, the words (up to a
      certain length) are enumerated more or less exhaustively and are individually
      checked in terms of observed and expected frequencies, variances, and scores of
      discrepancy and significance thereof. Here we take the global approach of
      annotating the suffix tree of a sequence with some such values and scores, having
      in mind to use it as a collective detector of all unexpected behaviors, or
      perhaps just as a preliminary filter for words suspicious enough to undergo a
      more accurate scrutiny. We consider in depth the simple probabilistic model in
      which sequences are produced by a random source emitting symbols from a known
      alphabet independently and according to a given distribution. Our main result
      consists of showing that, within this model, full tree annotations can be carried
      out in a time-and-space optimal fashion for the mean, variance and some of the
      adopted measures of significance. This result is achieved by an ad hoc embedding
      in statistical expressions of the combinatorial structure of the periods of a
      string. Specifically, we show that the expected value and variance of all
      substrings in a given sequence of n symbols can be computed and stored in
      (optimal) O(n2) overall worst-case, O (n log n) expected time and space. The O
      (n2) time bound constitutes an improvement by a linear factor over direct
      methods. Moreover, we show that under several accepted measures of deviation from
      expected frequency, the candidates over- or underrepresented words are restricted
      to the O(n) words that end at internal nodes of a compact suffix tree, as opposed
      to the theta(n2) possible substrings. This surprising fact is a consequence of
      properties in the form that if a word that ends in the middle of an arc is, say,
      overrepresented, then its extension to the nearest node of the tree is even more
      so. Based on this, we design global detectors of favored and unfavored words for
      our probabilistic framework in overall linear time and space, discuss related
      software implementations and display the results of preliminary experiments.

PMID- 10890390
TI  - A discriminative framework for detecting remote protein homologies.
AB  - A new method for detecting remote protein homologies is introduced and shown to
      perform well in classifying protein domains by SCOP superfamily. The method is a
      variant of support vector machines using a new kernel function. The kernel
      function is derived from a generative statistical model for a protein family, in
      this case a hidden Markov model. This general approach of combining generative
      models like HMMs with discriminative methods such as support vector machines may
      have applications in other areas of biosequence analysis as well.

PMID- 10890391
TI  - Scaling laws and similarity detection in sequence alignment with gaps.
AB  - We study the problem of similarity detection by sequence alignment with gaps,
      using a recently established theoretical framework based on the morphology of
      alignment paths. Alignments of sequences without mutual correlations are found to
      have scale-invariant statistics. This is the basis for a scaling theory of
      alignments of correlated sequences. Using a simple Markov model of evolution, we
      generate sequences with well-defined mutual correlations and quantify the
      fidelity of an alignment in an unambiguous way. The scaling theory predicts the
      dependence of the fidelity on the alignment parameters and on the statistical
      evolution parameters characterizing the sequence correlations. Specific criteria
      for the optimal choice of alignment parameters emerge from this theory. The
      results are verified by extensive numerical simulations.

PMID- 10890392
TI  - Estimation of the mutation rate during error-prone polymerase chain reaction.
AB  - Error-prone polymerase chain reaction (PCR) is widely used to introduce point
      mutations during in vitro evolution experiments. Accurate estimation of the
      mutation rate during error-prone PCR is important in studying the diversity of
      error-prone PCR product. Although many methods for estimating the mutation rate
      during PCR are available, all the existing methods depend on the assumption that
      the mutation rate is low and mutations occur at different places whenever they
      occur. The available methods may not be applicable to estimate the mutation rate
      during error-prone PCR. We develop a mathematical model for error-prone PCR and
      present methods to estimate the mutation rate during error-prone PCR without
      assuming low mutation rate. We also develop a computer program to simulate error
      prone PCR. Using the program, we compare the newly developed methods with two
      other methods. We show that when the mutation rate is relatively low (< 10(-3)
      per base per PCR cycle), the newly developed methods give roughly the same
      results as previous methods. When the mutation rate is relatively high (> 5 x 10(
      3) per base per PCR cycle, the mutation rate for most error-prone PCR
      experiments), the previous methods underestimate the mutation rate and the newly
      developed methods approximate the true mutation rate.

PMID- 10890393
TI  - A Bayesian model for detecting past recombination events in DNA multiple
      alignments.
AB  - Most phylogenetic tree estimation methods assume that there is a single set of
      hierarchical relationships among sequences in a data set for all sites along an
      alignment. Mosaic sequences produced by past recombination events will violate
      this assumption and may lead to misleading results from a phylogenetic analysis
      due to the imposition of a single tree along the entire alignment. Therefore, the
      detection of past recombination is an important first step in an analysis. A
      Bayesian model for the changes in topology caused by recombination events is
      described here. This model relaxes the assumption of one topology for all sites
      in an alignment and uses the theory of Hidden Markov models to facilitate
      calculations, the hidden states being the underlying topologies at each site in
      the data set. Changes in topology along the multiple sequence alignment are
      estimated by means of the maximum a posteriori (MAP) estimate. The performance of
      the MAP estimate is assessed by application of the model to data sets of four
      sequences, both simulated and real.

PMID- 10890394
TI  - Prediction of RNA base pairing probabilities on massively parallel computers.
AB  - We present an implementation of McCaskill's algorithm for computing the base pair
      probabilities of an RNA molecule for massively parallel message passing
      architectures. The program can be used to routinely fold RNA sequences of more
      than 10,000 nucleotides. Applications to complete viral genomes are discussed.

PMID- 10890395
TI  - Hierarchy of regions of amino acid sequence with respect to their role in the
      protein spatial structure.
AB  - The method of the representation of amino acid sequence by graph of the
      interactions energy between parts of spatial structure has been elaborated. Our
      method provides the possibility to establish the compatibility between each point
      of a polypeptide chain and the Van der Waals interactions energy of regions of a
      native globule adjacent to this amino acid residue. We have undertaken an
      exhaustive analysis of a set of proteins. Boundaries of domain and module
      structures have been found. Nonequivalence of different parts of sequences in
      respect to their contribution to stabilization of the spatial structure of the
      protein macromolecules has been revealed. On the basis of the number of energetic
      levels which are necessary to identify all independent parts of the globule, the
      contribution from each part of the sequence to stabilization of the spatial
      structure of the globule is defined. Thus, it has been found that the sequence of
      amino acid residues coincides with the sequence of the numerical values which can
      be used in turn in formal procedures, such as an alignment, a search of
      consensus, the recognition of composition peculiarities, etc. An example of the
      comparison of proteins with various sequence identities is considered to
      demonstrate the scheme of an alignment procedure.

PMID- 10890396
TI  - An overview on the distribution of word counts in Markov chains.
AB  - In this paper, we give an overview about the different results existing on the
      statistical distribution of word counts in a Markovian sequence of letters.
      Results concerning the number of overlapping occurrences, the number of renewals
      and the number of clumps will be presented. Counts of single words and also
      multiple words are considered. Most of the results are approximations as the
      length of the sequence tends to infinity. We will see that Gaussian
      approximations switch to (compound) Poisson approximations for rare words.
      Modeling DNA sequences or proteins by stationary Markov chains, these results can
      be used to study the statistical frequency of motifs in a given sequence.

PMID- 10890397
TI  - A greedy algorithm for aligning DNA sequences.
AB  - For aligning DNA sequences that differ only by sequencing errors, or by
      equivalent errors from other sources, a greedy algorithm can be much faster than
      traditional dynamic programming approaches and yet produce an alignment that is
      guaranteed to be theoretically optimal. We introduce a new greedy alignment
      algorithm with particularly good performance and show that it computes the same
      alignment as does a certain dynamic programming algorithm, while executing over
      10 times faster on appropriate data. An implementation of this algorithm is
      currently used in a program that assembles the UniGene database at the National
      Center for Biotechnology Information.

PMID- 10890399
TI  - Bayesian segmentation of protein secondary structure.
AB  - We present a novel method for predicting the secondary structure of a protein
      from its amino acid sequence. Most existing methods predict each position in turn
      based on a local window of residues, sliding this window along the length of the
      sequence. In contrast, we develop a probabilistic model of protein
      sequence/structure relationships in terms of structural segments, and formulate
      secondary structure prediction as a general Bayesian inference problem. A
      distinctive feature of our approach is the ability to develop explicit
      probabilistic models for alpha-helices, beta-strands, and other classes of
      secondary structure, incorporating experimentally and empirically observed
      aspects of protein structure such as helical capping signals, side chain
      correlations, and segment length distributions. Our model is Markovian in the
      segments, permitting efficient exact calculation of the posterior probability
      distribution over all possible segmentations of the sequence using dynamic
      programming. The optimal segmentation is computed and compared to a predictor
      based on marginal posterior modes, and the latter is shown to provide significant
      improvement in predictive accuracy. The marginalization procedure provides exact
      secondary structure probabilities at each sequence position, which are shown to
      be reliable estimates of prediction uncertainty. We apply this model to a
      database of 452 nonhomologous structures, achieving accuracies as high as the
      best currently available methods. We conclude by discussing an extension of this
      framework to model nonlocal interactions in protein structures, providing a
      possible direction for future improvements in secondary structure prediction
      accuracy.

PMID- 10890398
TI  - DNA segmentation through the Bayesian approach.
AB  - We present a new approach to DNA segmentation into compositionally homogeneous
      blocks. The Bayesian estimator, which is applicable for both short and long
      segments, is used to obtain the measure of homogeneity. An exact optimal
      segmentation is found via the dynamic programming technique. After completion of
      the segmentation procedure, the sequence composition on different scales can be
      analyzed with filtration of boundaries via the partition function approach.

PMID- 10890400
TI  - Translation conditional models for protein coding sequences.
AB  - A coding sequence is defined as a DNA sequence coding the primary structure of a
      protein (a polypeptide). Such a sequence must satisfy a specific constraint,
      which consists in coding a functional protein. As the genetic code is
      degenerated, there exists, for a given polypeptide, a set of synonymous sequences
      which would code the same polypeptide. Translation conditional models are being
      defined on such sets. The aim of this paper is to give a common formalism.
      Besides the codon bias model, a few other conditional models will be defined.
      Statistical estimators and comparison methods will be briefly presented. These
      models can be used for gene classification, or to find out, in a real sequence,
      remarkable features. An example will be presented on Escherichia coli genes.

PMID- 10890401
TI  - Evaluation measures of multiple sequence alignments.
AB  - Multiple sequence alignments (MSAs) are frequently used in the study of families
      of protein sequences or DNA/RNA sequences. They are a fundamental tool for the
      understanding of the structure, functionality and, ultimately, the evolution of
      proteins. A new algorithm, the Circular Sum (CS) method, is presented for
      formally evaluating the quality of an MSA. It is based on the use of a solution
      to the Traveling Salesman Problem, which identifies a circular tour through an
      evolutionary tree connecting the sequences in a protein family. With this
      approach, the calculation of an evolutionary tree and the errors that it would
      introduce can be avoided altogether. The algorithm gives an upper bound, the best
      score that can possibly be achieved by any MSA for a given set of protein
      sequences. Alternatively, if presented with a specific MSA, the algorithm
      provides a formal score for the MSA, which serves as an absolute measure of the
      quality of the MSA. The CS measure yields a direct connection between an MSA and
      the associated evolutionary tree. The measure can be used as a tool for
      evaluating different methods for producing MSAs. A brief example of the last
      application is provided. Because it weights all evolutionary events on a tree
      identically, but does not require the reconstruction of a tree, the CS algorithm
      has advantages over the frequently used sum-of-pairs measures for scoring MSAs,
      which weight some evolutionary events more strongly than others. Compared to
      other weighted sum-of-pairs measures, it has the advantage that no evolutionary
      tree must be constructed, because we can find a circular tour without knowing the
      tree.

PMID- 10890402
TI  - Metrics on RNA secondary structures.
AB  - Many different programs have been developed for the prediction of the secondary
      structure of an RNA sequence. Some of these programs generate an ensemble of
      structures, all of which have free energy close to that of the optimal structure,
      making it important to be able to quantify how similar these different structures
      are. To deal with this problem, we define a new class of metrics, the mountain
      metrics, on the set of RNA secondary structures of a fixed length. We compare
      properties of these metrics with other well known metrics on RNA secondary
      structures. We also study some global and local properties of these metrics.

PMID- 10890403
TI  - Winnowing sequences from a database search.
AB  - In database searches for sequence similarity, matches to a distinct sequence
      region (e.g., protein domain) are frequently obscured by numerous matches to
      another region of the same sequence. In order to cope with this problem,
      algorithms are developed to discard redundant matches. One model for this problem
      begins with a list of intervals, each with an associated score; each interval
      gives the range of positions in the query sequence that align to a database
      sequence, and the score is that of the alignment. If interval I is contained in
      interval J, and I's score is less than J's, then I is said to be dominated by J.
      The problem is then to identify each interval that is dominated by at least K
      other intervals, where K is a given level of "tolerable redundancy." An algorithm
      is developed to solve the problem in O(N log N) time and O(N*) space, where N is
      the number of intervals and N* is a precisely defined value that never exceeds N
      and is frequently much smaller. This criterion for discarding database hits has
      been implemented in the Blast program, as illustrated herein with examples.
      Several variations and extensions of this approach are also described.

PMID- 10890404
TI  - Algorithms for optical mapping.
AB  - Optical mapping is a novel technique for determining the restriction sites on a
      DNA molecule by directly observing a number of partially digested copies of the
      molecule under a light microscope. The problem is complicated by uncertainty as
      to the orientation of the molecules and by erroneous detection of cuts. In this
      paper we study the problem of constructing a restriction map based on optical
      mapping data. We give several variants of a polynomial reconstruction algorithm,
      as well as an algorithm that is exponential in the number of cut sites, and hence
      is appropriate only for small number of cut sites. We give a simple probabilistic
      model for data generation and for the errors and prove probabilistic upper and
      lower bounds on the number of molecules needed by each algorithm in order to
      obtain a correct map, expressed as a function of the number of cut sites and the
      error parameters. To the best of our knowledge, this is the first probabilistic
      analysis of algorithms for the problem. We also provide experimental results
      confirming that our algorithms are highly effective on simulated data.

PMID- 10890406
TI  - Human genome projects: work in progress.

PMID- 10890405
TI  - Detection of protein coding sequences using a mixture model for local protein
      amino acid sequence.
AB  - Locating protein coding regions in genomic DNA is a critical step in accessing
      the information generated by large scale sequencing projects. Current methods for
      gene detection depend on statistical measures of content differences between
      coding and noncoding DNA in addition to the recognition of promoters, splice
      sites, and other regulatory sites. Here we explore the potential value of
      recurrent amino acid sequence patterns 3-19 amino acids in length as a content
      statistic for use in gene finding approaches. A finite mixture model
      incorporating these patterns can partially discriminate protein sequences which
      have no (detectable) known homologs from randomized versions of these sequences,
      and from short (< or = 50 amino acids) non-coding segments extracted from the S.
      cerevisiea genome. The mixture model derived scores for a collection of human
      exons were not correlated with the GENSCAN scores, suggesting that the addition
      of our protein pattern recognition module to current gene recognition programs
      may improve their performance.

PMID- 10890407
TI  - Bad clinical practices.

PMID- 10890408
TI  - World leaders heap praise on human genome landmark.

PMID- 10890409
TI  - Draft data leave geneticists with a mountain still to climb.

PMID- 10890411
TI  - 'Dolly' team wins further patents.

PMID- 10890410
TI  - Call for monitoring plan on German GM crops.

PMID- 10890413
TI  - Astronomers fume over night light

PMID- 10890412
TI  - Martian gullies tempt NASA to look for water.

PMID- 10890414
TI  - Educated US public get more wary of genetic engineering.

PMID- 10890415
TI  - Call for more accelerator research

PMID- 10890416
TI  - Patent suit on Alzheimer's mouse rejected...but controversy over rights lingers
      on.

PMID- 10890418
TI  - Pasteur Institute to abandon departmental structure?

PMID- 10890417
TI  - UK studies ways of paying to join Chile observatory

PMID- 10890419
TI  - Feathers fly in Beijing.

PMID- 10890420
TI  - Africa needs locally trained soil specialists to improve land use.

PMID- 10890421
TI  - Did Greeks beat Chinese on blood circulation...

PMID- 10890422
TI  - Or was 'blood as the river of life' just poetic?

PMID- 10890423
TI  - The microscope's coat of arms...or, the sting of the bee and the moons of
      Jupiter.

PMID- 10890424
TI  - Tuberculosis bacteria join UN

PMID- 10890425
TI  - Critical time for fluid dynamos

PMID- 10890427
TI  - Condensed-matter physics. Misbehaviour in metals

PMID- 10890426
TI  - Genetics. Targeting sheep.

PMID- 10890428
TI  - Linguistics. Talking trees tell tales.

PMID- 10890429
TI  - The cosmic origin of deuterium.

PMID- 10890430
TI  - Neurobiology. Translating activity into plasticity.

PMID- 10890431
TI  - Conditioning and opiate withdrawal.

PMID- 10890432
TI  - Enzymatic production of biohydrogen.

PMID- 10890433
TI  - Malaria susceptibility and CD36 mutation.

PMID- 10890434
TI  - Species status of hybridizing oaks.

PMID- 10890435
TI  - Effect of aquaculture on world fish supplies.
AB  - Global production of farmed fish and shellfish has more than doubled in the past
      15 years. Many people believe that such growth relieves pressure on ocean
      fisheries, but the opposite is true for some types of aquaculture. Farming
      carnivorous species requires large inputs of wild fish for feed. Some aquaculture
      systems also reduce wild fish supplies through habitat modification, wild
      seedstock collection and other ecological impacts. On balance, global aquaculture
      production still adds to world fish supplies; however, if the growing aquaculture
      industry is to sustain its contribution to world fish supplies, it must reduce
      wild fish inputs in feed and adopt more ecologically sound management practices.

PMID- 10890436
TI  - Deuterium in the Galactic Centre as a result of recent infall of low-metallicity
      gas.
AB  - The Galactic Centre is the most active and heavily processed region of the Milky
      Way, so it can be used as a stringent test for the abundance of deuterium (a
      sensitive indicator of conditions in the first 1,000 seconds in the life of the
      Universe). As deuterium is destroyed in stellar interiors, chemical evolution
      models predict that its Galactic Centre abundance relative to hydrogen is D/H = 5
      x 10(-12), unless there is a continuous source of deuterium from relatively
      primordial (low-metallicity) gas. Here we report the detection of deuterium (in
      the molecule DCN) in a molecular cloud only 10 parsecs from the Galactic Centre.
      Our data, when combined with a model of molecular abundances, indicate that D/H =
      (1.7 +/- 0.3) x 10(-6), five orders of magnitude larger than the predictions of
      evolutionary models with no continuous source of deuterium. The most probable
      explanation is recent infall of relatively unprocessed metal-poor gas into the
      Galactic Centre (at the rate inferred by Wakker). Our measured D/H is nine times
      less than the local interstellar value, and the lowest D/H observed in the
      Galaxy. We conclude that the observed Galactic Centre deuterium is cosmological,
      with an abundance reduced by stellar processing and mixing, and that there is no
      significant Galactic source of deuterium.

PMID- 10890437
TI  - The mean free path for electron conduction in metallic fullerenes
AB  - The electrical resistivity, p, of a metal is usually interpreted in terms of the
      mean free path (the average distance, l, an electron travels before it is
      scattered). As the temperature is raised, the resistivity increases and the
      apparent mean free path is correspondingly reduced. In this semi-classical
      picture, the mean free path cannot be much shorter than the distance, d, between
      two atoms. This has been confirmed for many systems and was considered to be a
      universal behaviour. Recently, some apparent exceptions were found, including
      alkali-doped fullerenes and high-temperature superconductors. However, there
      remains the possibility that these systems are in exotic states, with only a
      small fraction of the conduction electrons contributing to the conductivity; the
      mean free path would then have to be correspondingly larger to explain the
      observed resistivity. Here we report a model calculation of electron conduction
      in alkali-doped fullerenes, in which the electrons are scattered by
      intramolecular vibrations. The resistivity at large temperatures implies l << d,
      demonstrating that there is no fundamental principle requiring l > or = d. At
      high temperatures, the semi-classical picture breaks down, and the electrons
      cannot be described as quasiparticles.

PMID- 10890438
TI  - Collapse of stiff conjugated polymers with chemical defects into ordered,
      cylindrical conformations
AB  - The optical, electronic and mechanical properties of synthetic and biological
      materials consisting of polymer chains depend sensitively on the conformation
      adopted by these chains. The range of conformations available to such systems has
      accordingly been of intense fundamental as well as practical interest, and
      distinct conformational classes have been predicted, depending on the stiffness
      of the polymer chains and the strength of attractive interactions between
      segments within a chain. For example, flexible polymers should adopt highly
      disordered conformations resembling either a random coil or, in the presence of
      strong intrachain attractions, a so-called 'molten globule'. Stiff polymers with
      strong intrachain interactions, in contrast, are expected to collapse into
      conformations with long-range order, in the shape of toroids or rod-like
      structures. Here we use computer simulations to show that the anisotropy
      distribution obtained from polarization spectroscopy measurements on individual
      poly[2-methoxy-5-(2'-ethylhexyl)oxy-1,4-phenylenevinylene] polymer molecules is
      consistent with this prototypical stiff conjugated polymer adopting a highly
      ordered, collapsed conformation that cannot be correlated with ideal toroid or
      rod structures. We find that the presence of so-called 'tetrahedral chemical
      defects', where conjugated carbon-carbon links are replaced by tetrahedral links,
      divides the polymer chain into structurally identifiable quasi-straight segments
      that allow the molecule to adopt cylindrical conformations. Indeed, highly
      ordered, cylindrical conformations may be a critical factor in dictating the
      extraordinary photophysical properties of conjugated polymers, including highly
      efficient intramolecular energy transfer and significant local optical anisotropy
      in thin films.

PMID- 10890439
TI  - Dynamic self-assembly of magnetized, millimetre-sized objects rotating at a
      liquid-air interface
AB  - Spontaneous pattern formation by self-assembly is of long-standing and continuing
      interest not only for its aesthetic appeal, but also for its fundamental and
      technological relevance. So far, the study of self-organization processes has
      mainly focused on static structures, but dynamic systems--those that develop
      order only when dissipating energy--are of particular interest for studying
      complex behaviour. Here we describe the formation of dynamic patterns of
      millimetre-sized magnetic disks at a liquid-air interface, subject to a magnetic
      field produced by a rotating permanent magnet. The disks spin around their axes
      with angular frequency equal to that of the magnet, and are attracted towards its
      axis of rotation while repelling each other. This repulsive hydrodynamic
      interaction is due to fluid motion associated with spinning; the interplay
      between attractive and repulsive interactions leads to the formation of patterns
      exhibiting various types of ordering, some of which are entirely new. This
      versatile system should lead to a better understanding of dynamic self-assembly,
      while providing a test-bed for stability theories of interacting point vortices
      and vortex patches.

PMID- 10890440
TI  - Structural basis for the fracture toughness of the shell of the conch Strombus
      gigas.
AB  - Natural composite materials are renowned for their mechanical strength and
      toughness: despite being highly mineralized, with the organic component
      constituting not more than a few per cent of the composite material, the fracture
      toughness exceeds that of single crystals of the pure mineral by two to three
      orders of magnitude. The judicious placement of the organic matrix, relative to
      the mineral phase, and the hierarchical structural architecture extending over
      several distinct length scales both play crucial roles in the mechanical response
      of natural composites to external loads. Here we use transmission electron
      microscopy studies and beam bending experiments to show that the resistance of
      the shell of the conch Strombus gigas to catastrophic fracture can be understood
      quantitatively by invoking two energy-dissipating mechanisms: multiple
      microcracking in the outer layers at low mechanical loads, and crack bridging in
      the shell's tougher middle layers at higher loads. Both mechanisms are intimately
      associated with the so-called crossed lamellar microarchitecture of the shell,
      which provides for 'channel' cracking in the outer layers and uncracked
      structural features that bridge crack surfaces, thereby significantly increasing
      the work of fracture, and hence the toughness, of the material. Despite a high
      mineral content of about 99% (by volume) of aragonite, the shell of Strombus
      gigas can thus be considered a 'ceramic plywood' and can guide the biomimetic
      design of tough, lightweight structures.

PMID- 10890441
TI  - Palaeotemperature reconstruction from noble gases in ground water taking into
      account equilibration with entrapped air
AB  - Noble-gas concentrations in ground water have been used as a proxy for past air
      temperatures, but the accuracy of this approach has been limited by the existence
      of a temperature-independent component of the noble gases in ground water, termed
      'excess air' whose origin and composition is poorly understood. In particular,
      the evidence from noble gases in a Brazilian aquifer for a cooling of more than 5
      C in tropical America during the Last Glacial Maximum has been called into
      question. Here we propose a model for dissolved gases in ground water, which
      describes the formation of excess air by equilibration of ground water with
      entrapped air in quasi-saturated soils. Our model predicts previously unexplained
      noble-gas data sets, including the concentration of atmospheric helium, and
      yields consistent results for the non-atmospheric helium isotopes that are used
      for dating ground water. Using this model of excess air, we re-evaluate the use
      of noble gases from ground water for reconstructing past temperatures. Our
      results corroborate the inferred cooling in Brazil during the Last Glacial
      Maximum, and indicate that even larger cooling took place at mid-latitudes.

PMID- 10890442
TI  - The plastic deformation of iron at pressures of the Earth's inner core
AB  - Soon after the discovery of seismic anisotropy in the Earth's inner core, it was
      suggested that crystal alignment attained during deformation might be
      responsible. Since then, several other mechanisms have been proposed to account
      for the observed anisotropy, but the lack of deformation experiments performed at
      the extreme pressure conditions corresponding to the solid inner core has limited
      our ability to determine which deformation mechanism applies to this region of
      the Earth. Here we determine directly the elastic and plastic deformation
      mechanism of iron at pressures of the Earth's core, from synchrotron X-ray
      diffraction measurements of iron, under imposed axial stress, in diamond-anvil
      cells. The epsilon-iron (hexagonally close packed) crystals display strong
      preferred orientation, with c-axes parallel to the axis of the diamond-anvil
      cell. Polycrystal plasticity theory predicts an alignment of c-axes parallel to
      the compression direction as a result of basal slip, if basal slip is either the
      primary or a secondary slip system. The experiments provide direct observations
      of deformation mechanisms that occur in the Earth's inner core, and introduce a
      method for investigating, within the laboratory, the rheology of materials at
      extreme pressures.

PMID- 10890443
TI  - Ecosystem size determines food-chain length in lakes.
AB  - Food-chain length is an important characteristic of ecological communities: it
      influences community structure, ecosystem functions and contaminant
      concentrations in top predators. Since Elton first noted that food-chain length
      was variable among natural systems, ecologists have considered many explanatory
      hypotheses, but few are supported by empirical evidence. Here we test three
      hypotheses that predict food-chain length to be determined by productivity alone
      (productivity hypothesis), ecosystem size alone (ecosystem-size hypothesis) or a
      combination of productivity and ecosystem size (productive-space hypothesis). The
      productivity and productive-space hypotheses propose that food-chain length
      should increase with increasing resource availability; however, the productivity
      hypothesis does not include ecosystem size as a determinant of resource
      availability. The ecosystem-size hypothesis is based on the relationship between
      ecosystem size and species diversity, habitat availability and habitat
      heterogeneity. We find that food-chain length increases with ecosystem size, but
      that the length of the food chain is not related to productivity. Our results
      support the hypothesis that ecosystem size, and not resource availability,
      determines food-chain length in these natural ecosystems.

PMID- 10890444
TI  - Cryptophyte algae are robbed of their organelles by the marine ciliate Mesodinium
      rubrum.
AB  - Mesodinium rubrum (Lohmann 1908) Jankowski 1976 (= Myrionecta rubra) is a common
      photosynthetic marine planktonic ciliate which can form coastal red-tides. It may
      represent a 'species complex' and since Darwin's voyage on the Beagle, it has
      been of great cytological, physiological and evolutionary interest. It is
      considered to be functionally a phytoplankter because it was thought to have lost
      the capacity to feed and possesses a highly modified algal endosymbiont. Whether
      M. rubrum is the result of a permanent endosymbiosis or a transient association
      between a ciliate and an alga is controversial. We conducted 'feeding'
      experiments to determine how exposure to a cryptophyte alga affects M. rubrum.
      Here we show that although M. rubrum lacks a cytostome (oral cavity), it ingests
      cryptophytes and steals their organelles, and may not maintain a permanent
      endosymbiont. M. rubrum does not fall into recognized cellular or functional
      categories, but may be a chimaera partially supported by organelle robbery.

PMID- 10890445
TI  - Language trees support the express-train sequence of Austronesian expansion.
AB  - Languages, like molecules, document evolutionary history. Darwin observed that
      evolutionary change in languages greatly resembled the processes of biological
      evolution: inheritance from a common ancestor and convergent evolution operate in
      both. Despite many suggestions, few attempts have been made to apply the
      phylogenetic methods used in biology to linguistic data. Here we report a
      parsimony analysis of a large language data set. We use this analysis to test
      competing hypotheses--the "express-train" and the "entangled-bank" models--for
      the colonization of the Pacific by Austronesian-speaking peoples. The parsimony
      analysis of a matrix of 77 Austronesian languages with 5,185 lexical items
      produced a single most-parsimonious tree. The express-train model was converted
      into an ordered geographical character and mapped onto the language tree. We
      found that the topology of the language tree was highly compatible with the
      express-train model.

PMID- 10890446
TI  - Mosaic evolution of brain structure in mammals.
AB  - The mammalian brain comprises a number of functionally distinct systems. It might
      therefore be expected that natural selection on particular behavioural capacities
      would have caused size changes selectively, in the systems mediating those
      capacities. It has been claimed, however, that developmental constraints limited
      such mosaic evolution, causing co-ordinated size change among individual brain
      components. Here we analyse comparative data to demonstrate that mosaic change
      has been an important factor in brain structure evolution. First, the neocortex
      shows about a fivefold difference in volume between primates and insectivores
      even after accounting for its scaling relationship with the rest of the brain.
      Second, brain structures with major anatomical and functional links evolved
      together independently of evolutionary change in other structures. This is true
      at the level of both basic brain subdivisions and more fine-grained functional
      systems. Hence, brain evolution in these groups involved complex relationships
      among individual brain components.

PMID- 10890447
TI  - The temporal response of the brain after eating revealed by functional MRI.
AB  - After eating, the human brain senses a biochemical change and then signals
      satiation, but precisely when this occurs is unknown. Even for well-established
      physiological systems like glucose-insulin regulation, the timing of interaction
      between hormonal processes and neural events is inferred mostly from blood
      sampling. Recently, neuroimaging studies have provided in vivo information about
      the neuroanatomical correlates of the regulation of energy intake. Temporal
      orchestration of such systems, however, is crucial to the integration of neuronal
      and hormonal signals that control eating behaviour. The challenge of this
      functional magnetic resonance imaging study is to map not only where but also
      when the brain will respond after food ingestion. Here we use a temporal
      clustering analysis technique to demonstrate that eating-related neural activity
      peaks at two different times with distinct localization. Importantly, the
      differentiated responses are interacting with an internal signal, the plasma
      insulin. These results support the concept of temporal parcellation of brain
      activity, which reflects the different natures of stimuli and responses.
      Moreover, this study provides a neuroimaging basis for detecting dynamic
      processes without prior knowledge of their timing, such as the acute effects of
      medication and nutrition in the brain.

PMID- 10890448
TI  - Postsynaptic translation affects the efficacy and morphology of neuromuscular
      junctions.
AB  - Long-term synaptic plasticity may be associated with structural rearrangements
      within the neuronal circuitry. Although the molecular mechanisms governing such
      activity-controlled morphological alterations are mostly elusive, polysomal
      accumulations at the base of developing dendritic spines and the activity-induced
      synthesis of synaptic components suggest that localized translation is involved
      during synaptic plasticity. Here we show that large aggregates of translational
      components as well as messenger RNA of the postsynaptic glutamate receptor
      subunit DGluR-IIA are localized within subsynaptic compartments of larval
      neuromuscular junctions of Drosophila melanogaster. Genetic models of junctional
      plasticity and genetic manipulations using the translation initiation factors
      eIF4E and poly(A)-binding protein showed an increased occurrence of subsynaptic
      translation aggregates. This was associated with a significant increase in the
      postsynaptic DGluR-IIA protein levels and a reduction in the junctional
      expression of the cell-adhesion molecule Fasciclin II. In addition, the efficacy
      of junctional neurotransmission and the size of larval neuromuscular junctions
      were significantly increased. Our results therefore provide evidence for a
      postsynaptic translational control of long-term junctional plasticity.

PMID- 10890449
TI  - Production of gene-targeted sheep by nuclear transfer from cultured somatic
      cells.
AB  - It is over a decade since the first demonstration that mouse embryonic stem cells
      could be used to transfer a predetermined genetic modification to a whole animal.
      The extension of this technique to other mammalian species, particularly
      livestock, might bring numerous biomedical benefits, for example, ablation of
      xenoreactive transplantation antigens, inactivation of genes responsible for
      neuropathogenic disease and precise placement of transgenes designed to produce
      proteins for human therapy. Gene targeting has not yet been achieved in mammals
      other than mice, however, because functional embryonic stem cells have not been
      derived. Nuclear transfer from cultured somatic cells provides an alternative
      means of cell-mediated transgenesis. Here we describe efficient and reproducible
      gene targeting in fetal fibroblasts to place a therapeutic transgene at the ovine
      alpha1(I) procollagen (COL1A1) locus and the production of live sheep by nuclear
      transfer.

PMID- 10890450
TI  - Gigantism in mice lacking suppressor of cytokine signalling-2.
AB  - Suppressor of cytokine signalling-2 (SOCS-2) is a member of the suppressor of
      cytokine signalling family, a group of related proteins implicated in the
      negative regulation of cytokine action through inhibition of the Janus kinase
      (JAK) signal transducers and activators of transcription (STAT) signal
      transduction pathway. Here we use mice unable to express SOCS-2 to examine its
      function in vivo. SOCS-2(-/-) mice grew significantly larger than their wild-type
      littermates. Increased body weight became evident after weaning and was
      associated with significantly increased long bone lengths and the proportionate
      enlargement of most organs. Characteristics of deregulated growth hormone and
      insulin-like growth factor-I (IGF-I) signalling, including decreased production
      of major urinary protein, increased local IGF-I production, and collagen
      accumulation in the dermis, were observed in SOCS-2-deficient mice, indicating
      that SOCS-2 may have an essential negative regulatory role in the growth
      hormone/IGF-I pathway.

PMID- 10890451
TI  - Crystal structure of enteropathogenic Escherichia coli intimin-receptor complex.
AB  - Intimin and its translocated intimin receptor (Tir) are bacterial proteins that
      mediate adhesion between mammalian cells and attaching and effacing (A/E)
      pathogens. Enteropathogenic Escherichia coli (EPEC) causes significant paediatric
      morbidity and mortality world-wide. A related A/E pathogen, enterohaemorrhagic E.
      coli (EHEC; O157:H7) is one of the most important food-borne pathogens in North
      America, Europe and Japan. A unique and essential feature of A/E bacterial
      pathogens is the formation of actin-rich pedestals beneath the intimately
      adherent bacteria and localized destruction of the intestinal brush border. The
      bacterial outer membrane adhesin, intimin, is necessary for the production of the
      A/E lesion and diarrhoea. The A/E bacteria translocate their own receptor for
      intimin, Tir, into the membrane of mammalian cells using the type III secretion
      system. The translocated Tir triggers additional host signalling events and actin
      nucleation, which are essential for lesion formation. Here we describe the the
      crystal structures of an EPEC intimin carboxy-terminal fragment alone and in
      complex with the EPEC Tir intimin-binding domain, giving insight into the
      molecular mechanisms of adhesion of A/E pathogens.

PMID- 10890452
TI  - Solid-state NMR determination of the secondary structure of Samia cynthia ricini
      silk.
AB  - Silks are fibrous proteins that form heterogeneous, semi-crystalline solids. Silk
      proteins have a variety of physical properties reflecting their range of
      functions. Spider dragline silk, for example, has high tensile strength and
      elasticity, whereas other silks are better suited to making housing, egg sacs or
      the capture spiral of spiders' webs. The differing physical properties arise from
      variation in the protein's primary and secondary structure, and their packing in
      the solid phase. The high mechanical performance of spider dragline silk, for
      example, is probably due to a beta-sheet conformation of poly-alanine domains,
      embedded as small crystallites within the fibre. Only limited structural
      information can be obtained from diffraction of silks, so further
      characterization requires spectroscopic studies such as NMR. However, the
      classical approach to NMR structure determination fails because the high
      molecular weight, repetitive primary structure and structural heterogeneity of
      solid silk means that signals from individual amino-acid residues cannot be
      resolved. Here we adapt a recently developed solid-state NMR technique to
      determine torsion angle pairs (phi, psi) in the protein backbone, and we study
      the distribution of conformations in silk from the Eri silkworm, Samia cynthia
      ricini. Although the most probable conformation in native fibres is an anti
      parallel beta-sheet, film produced from liquid directly extracted from the silk
      glands appears to be primarily alpha-helical.

PMID- 10890453
TI  - Plasmid effects on Escherichia coli metabolism.
AB  - The idea that plasmids replicate within hosts at the expense of cell metabolic
      energy and preformed cellular blocks depicts plasmids as a kind of molecular
      parasites that, even when they may eventually provide plasmid-carrying strains
      with growth advantages over plasmid-free strains, doom hosts to bear an
      unavoidable metabolic burden. Due to the consistency with experimental data, this
      idea was rapidly adopted and used as a basis of different hypotheses to explain
      plasmid-host interactions. In this article we critically discuss current ideas
      about plasmid effects on host metabolism, and present evidence suggesting that
      the complex interaction between plasmids and hosts is related to the alteration
      of the cellular regulatory status.

PMID- 10890455
TI  - The learning laboratory.

PMID- 10890454
TI  - Membrane processing of fruit juices and beverages: a review.
AB  - Membrane technology for the processing of fruit juices and beverages has been
      applied mainly for clarification using ultrafiltration and microfiltration, and
      for concentration using reverse osmosis. The effects of product preparation,
      membrane selection, and operating parameters are important factors influencing
      filtration rate and product quality. Technological advances related to the
      development of new membranes, improvement in process engineering, and better
      understanding of fruit beverage constituents have expanded the range of membrane
      separation processes. Developments in novel membrane processes, including
      electrodialysis and pervaporation, increased the array of applications in
      combination with other technologies for alternate uses in fruit juices and
      beverages.

PMID- 10890456
TI  - Internal impingement in the shoulder of the overhand athlete: pathophysiology,
      diagnosis, and treatment.
AB  - The etiology of rotator cuff disease is multifactorial in nature. The process by
      which the articular surface of the rotator cuff can become diseased secondary to
      direct abutment against the glenoid rim and labrum has been termed internal
      impingement. Damage to the undersurface of the rotator cuff can occur from
      contact at the extremes of shoulder motion and can increase secondary to adaptive
      changes in bone and soft tissue. Diagnosis is achieved in most instances by a
      thorough physical examination. Adjunctive tests, particularly magnetic resonance
      imaging, can increase the accuracy of the diagnosis. If this disease is
      recognized early, nonoperative intervention may be successful. When nonoperative
      treatment fails, the use of arthroscopy for the treatment of torn rotator cuff
      and labral tissue and capsular laxity may be indicated to resolve symptoms and
      restore the premorbid level of function.

PMID- 10890457
TI  - Bupivacaine for postoperative pain relief at the iliac crest bone graft harvest
      site.
AB  - An inevitable side effect of iliac crest bone graft harvesting is postoperative
      pain at the donor site. Bupivacaine hydrochloride is a long-acting local
      anesthetic that is clinically effective for approximately 8 hours. The present
      study was undertaken to assess postoperative pain relief with locally injected
      bupivacaine at the iliac crest bone graft harvest site. Pain relief with locally
      injected bupivacaine or saline at the iliac bone harvest site using an indwelling
      catheter was studied in 13 patients in a prospective, double-blind, crossover
      study. Twelve patients had cervical diskectomy and arthrodesis with autograft and
      one patient had a triple arthrodesis of the foot. There were no statistically
      significant differences between patients given bupivacaine and patients given
      saline with respect to pain relief ratings and hip-pain ratings at rest and
      motion during the first 24-hour postoperative period and the second 24-hour
      postoperative period (Mann-Whitney test). The single diabetic patient who had a
      triple arthrodesis developed a wound infection at the catheter placement site.
      The number of patients was too small to draw conclusions about the differences in
      pain-medication requirements between patients undergoing single versus multiple
      diskectomies and fusions. In view of the lack of improvement in pain relief and
      the risk of infection, local administration of bupivacaine at the iliac bone
      harvest site is not recommended in its present form for postoperative analgesia.

PMID- 10890458
TI  - Persistent postoperative pain after the Chrisman-Snook ankle reconstruction.
AB  - One complication of the Chrisman-Snook ankle reconstruction is persistent
      postoperative pain. The incidence of this complication ranges from 7% to 60%. We
      report 10 cases of surgical exploration for persistent pain after Chrisman-Snook
      reconstructions. In 6 of the 10 cases a surgically correctable cause was found
      for the pain. The identified pathologic lesions in these 6 patients could have
      been prevented by careful attention to detail in the index operation. Surgical
      exploration should be considered for any of the following findings: persistent
      point tenderness (especially at the graft tunnel sites), localized swelling, a
      painful mass, recurrent instability/laxity, a symptomatic neuroma, or painful
      inversion and dorsiflexion. To prevent the complication of persistent
      postoperative pain after the Chrisman-Snook ankle reconstruction, we recommend
      the following: 1) avoid forced eversion when tensioning the graft, excessive
      posterior placement of the calcaneal tunnel, casting in eversion, and the use of
      nonabsorbable suture; 2) resect the distal muscle belly of the peroneus brevis
      muscle distal to the superior peroneal retinaculum; 3) check for tears in the
      peroneus brevis; 4) respect the sural nerve; and 5) obtain a watertight closure
      of the joint capsule. Although the Chrisman-Snook ankle reconstruction is an
      excellent technique, numerous pitfalls in surgical technique must be avoided.

PMID- 10890459
TI  - Location of the vertebral artery in the cervicothoracic junction.
AB  - Eight sectioned specimens and 8 cadavers were used to evaluate the location of
      the vertebral artery in the cervicothoracic junction. The results of the
      measurements showed that there was no significant difference between either sides
      at the C7-T1 junction in terms of all distances taken. The mean width of the
      vertebral artery was 2.9 mm at the levels of the C-7 and T-1. The sagittal
      distance between the vertebral artery and the posterior cortex was 16.8+/-3.0 mm
      at the C7 and 21.7+/-2.8 mm at T-1. The coronal distance between the vertebral
      artery and the midline of the vertebra was 17.5+/-1.8 mm at the C7 and 22.3+/-2.9
      mm at the T-1. The mean angle between the line connecting the lateral border of
      the vertebral artery with the posterior midway of the lateral mass and the
      parasagittal line at C-7 was 14.1+/-6.1 degrees. The mean angle of the vertebral
      artery with respect to the midline was 22.8+/-6.4 degrees. This study suggests
      that the vertebral artery has closer anatomic relationship to the C-7 lateral
      mass. Care should be taken to avoid injury to the vertebral artery if lateral
      mass screw fixation at the C-7 is intended.

PMID- 10890460
TI  - Adhesive capsulitis of the hip after bilateral adhesive capsulitis of the
      shoulder.
AB  - Adhesive capsulitis of the hip is a not a common clinical presentation. We report
      a case of adhesive capsulitis of the hip in a patient with hypothyroidism and
      previous adhesive capsulitis of the shoulder who was receiving thyroid-hormone
      replacement. The adhesive capsulitis of both hip and shoulder were treated
      successfully with physical therapy. Orthopedic surgeons should be aware of this
      diagnosis and its association with shoulder adhesive capsulitis and thyroid
      dysfunction, to allow them to recognize it and intervene early.

PMID- 10890461
TI  - Ulnar translocation instability of the carpus after a dorsal radiocarpal
      dislocation: a case report.
AB  - An unusual case of ulnar translocation of the carpus after a radiocarpal
      dislocation is described. Persistent instability was noted despite attempted
      reattachment of the avulsed palmar capsuloligamentous structures. A successful
      outcome occurred after radiolunate arthrodesis and external fixation of the
      wrist.

PMID- 10890462
TI  - Fibroma of tendon sheath involving the patellar tendon.
AB  - Fibroma of tendon sheath is a benign soft-tissue tumor that usually arises in
      association with tendons or ligamentous structures. We describe, what is, to the
      best of our knowledge, the first reported case of fibroma of tendon sheath
      involving the patellar tendon.

PMID- 10890463
TI  - Anterior cruciate ligament reconstruction: socioeconomic issues and cost
      effectiveness.
AB  - Anterior cruciate ligament ruptures continue to occur in increasing numbers.
      These injuries and their treatment create significant social and economic
      problems for patients, their physicians, and for society. By critically
      evaluating the trade-off between the costs and benefits of various treatment
      options, one can define a cost-effective approach to the management of this
      problem. Limited available data suggest that anterior cruciate ligament
      reconstruction is a highly cost-effective method of treatment for active young
      adults. The cost per additional quality-adjusted life year provided by surgery
      compares favorably with figures associated with other highly utilized health care
      interventions. Such data may prove invaluable within the context of health care
      reform.

PMID- 10890464
TI  - Hyphenated history: Knight-Taylor spinal orthosis.
AB  - This paper offers some interesting biographic information on the two men from
      whom the Knight-Taylor spinal orthosis takes its name. James Knight and Charles
      Taylor were two orthopedists from New York City who were interested in spinal
      care. They prescribed and fashioned their distinctive braces, aspects of which
      were combined by others, thus linking these two men in orthopedic hyphenated
      history.

PMID- 10890465
TI  - Discoid meniscus with degenerative tear.

PMID- 10890466
TI  - Risk management in major surgery III: myocardial injury following cardiac
      surgery.

PMID- 10890467
TI  - Overview of myocardial outcome: the interrelationships among coagulation,
      inflammation, and endothelium.

PMID- 10890468
TI  - Mechanisms of myocardial injury after cardiac surgery.

PMID- 10890469
TI  - Myocardial injury in cardiac surgery: the role of transfusion.
AB  - The approach to minimizing transfusion therapy in the cardiac surgical patient
      entails an understanding of the unique physiology of CPB. A comprehensive blood
      conservation program will promote autologous reinfusion techniques and
      pharmacologic agents that preserve hemostasis. The institution of therapy
      directed algorithms using appropriately selected tests will ultimately reduce
      empiric transfusions and will improve specificity of transfusion therapy. The use
      of technologies and drugs that attenuate inflammation will reduce consumption and
      the activation of leukocytes and platelets. This approach should be a
      multifaceted one that will ultimately lead to better preservation of end-organ
      function after cardiac surgery.

PMID- 10890470
TI  - Hemostatic product transfusions and adverse outcomes: focus on point-of-care
      testing to reduce transfusion need.

PMID- 10890471
TI  - Preservation and protection of myocardial function.

PMID- 10890472
TI  - Unfractionated heparin for cardiopulmonary bypass: an unnatural act?

PMID- 10890473
TI  - Recombinant hirudin as an alternative for anticoagulation during cardiopulmonary
      bypass in patients with heparin-induced thrombocytopenia type II: a 1-year
      experience in 57 patients.
AB  - OBJECTIVE: To explore the possible use of recombinant hirudin (r-hirudin) as an
      alternative to heparin for anticoagulation during cardiovascular surgery. DESIGN:
      Retrospective analysis. SETTING: Two university hospitals. PARTICIPANTS: Fifty
      seven patients with heparin-induced thrombocytopenia type II (HIT II) in whom r
      hirudin was used during cardiovascular surgery with cardiopulmonary bypass (CPB).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The r-hirudin concentration
      was monitored on-line, at the point of the patient's care using the ecarin
      clotting time and maintained in the range of 3 to 4 microg/mL. The r-hirudin
      elimination at the conclusion of CPB was augmented through modified zero-balanced
      ultrafiltration and forced diuresis. The duration of CPB was 63 to 246 minutes.
      The r-hirudin requirement per minute of CPB was 0.016 to 0.035 microg/kg/min, and
      the 24-hour blood drainage was 50 to 2,200 mL. Of the 57 patients, 54 fully
      recovered, including 9 patients who did not require any allogenic products. Four
      patients, all with impaired renal function, showed prolonged r-hirudin
      elimination and excessive bleeding and required surgical reexploration. Three
      patients died as a result of complications unrelated to the perioperative
      management. CONCLUSION: This study provides evidence that r-hirudin can be used
      safely and effectively for routine anticoagulation during CPB in patients
      diagnosed with HIT II. Almost 95% of the patients in whom it was used were
      discharged uneventfully. Patients with perioperative renal failure, however,
      showed increased bleeding.

PMID- 10890474
TI  - Hirudin monitoring using the TAS ecarin clotting time in patients with heparin
      induced thrombocytopenia type II.
AB  - OBJECTIVE: To assess the reliability of the TAS/ecarin clotting time (ECT) for on
      line monitoring of r-hirudin in cardiovascular surgery with and without
      cardiopulmonary bypass (CPB). DESIGN: Samples were spiked with r-hirudin (0 to 5
      microg/mL) and calibration curves constructed. Reproducibility was evaluated by
      measurement of the sample five times at each concentration. The influence of
      variations in hematocrit, plasma factors, and platelet count on the test results
      was examined. Samples were obtained from patients during cardiovascular surgery
      with CPB (n = 8), without CPB (n = 3), and from volunteers (n = 5) and compared
      with the laboratory reference tests. All tests were performed in duplicate.
      SETTING: Deutsches Herzzentrum Berlin. PARTICIPANTS: Five healthy volunteers and
      11 patients undergoing cardiovascular surgery. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: The TAS/ECT showed linearity and reliability to an r-hirudin
      concentration of 5 microg/mL and was not influenced (p < 0.005) by the varying
      conditions of the in vitro setup. The correlation to the laboratory method was
      0.74 for the CPB group and 0.87 for the non-CPB group. CONCLUSIONS: The TAS/ECT
      is a reliable assay for monitoring r-hirudin at the point of care. With this
      information, the use of r-hirudin during surgery or angioplasty should become
      more effective and safer.

PMID- 10890475
TI  - Effects of hemofiltration on serum aprotinin levels in patients undergoing
      cardiopulmonary bypass.
AB  - OBJECTIVE: To determine the effects of hemofiltration on serum aprotinin levels
      during cardiopulmonary bypass (CPB) surgery. DESIGN: Prospective, randomized
      study. SETTING: University of Washington Medical Center, single institution.
      PARTICIPANTS: Patients undergoing cardiac surgery without contraindications to
      aprotinin administration. INTERVENTIONS: Patients were randomized to full
      Hammersmith and half-Hammersmith dosing regimens of aprotinin and were further
      randomized to hemofiltration or no hemofiltration. MEASUREMENTS AND MAIN RESULTS:
      Serum aprotinin levels were studied before CPB, 60 and 120 minutes into CPB, and
      at the end of CPB before protamine administration. Each group experienced a
      decrease in serum aprotinin levels with the institution of CPB, attributable to
      hemodilution and redistribution of aprotinin outside of the vascular compartment.
      During CPB, aprotinin levels declined further, but no significant difference was
      observed between patients who received hemofiltration and those who did not.
      Hematocrit values were significantly higher at the end of CPB in the
      hemofiltration groups. Patients receiving half-Hammersmith dosing regimens
      maintained aprotinin levels throughout CPB, which have been shown to inhibit
      plasmin but were lower than levels previously shown to inhibit kallikrein.
      CONCLUSIONS: Hemofiltration during CPB did not significantly alter serum
      aprotinin levels in patients receiving half-Hammersmith and full-Hammersmith
      dosing regimens of aprotinin.

PMID- 10890476
TI  - Synthetic antifibrinolytics are not associated with an increased incidence of
      baffle fenestration closure after the modified Fontan procedure.
AB  - OBJECTIVE: To determine if the lysine analog antifibrinolytic agents, epsilon
      aminocaproic acid and tranexamic acid, are associated with early closure of the
      baffle fenestration after the modified Fontan procedure. DESIGN: Retrospective
      chart review. SETTING: University hospital. PARTICIPANTS: Seventy-four successive
      patients underwent the modified Fontan procedure. Three patients received
      aprotinin and were excluded. A total of 71 patients were analyzed. INTERVENTIONS:
      Charts were examined for variables known to be associated with baffle
      fenestration closure in the modified Fontan procedure. MEASUREMENTS AND MAIN
      RESULTS: Occurrence of baffle fenestration closure, oxygen saturation, central
      venous pressure, left atrial pressure, transpulmonary gradient, chest tube
      drainage volume, chest tube drainage duration, intensive care unit (ICU)
      duration, and total inpatient duration were compared between the 33 patients who
      received antifibrinolytics and the 38 patients who did not. One patient of 71 had
      baffle fenestration closure in the first 48 hours after surgery. Oxygen
      saturation, central venous pressure, left atrial pressure, transpulmonary
      gradient, chest tube drainage volume, chest tube drainage duration, days in ICU,
      and total inpatient duration were not significantly different between the two
      groups. CONCLUSIONS: Use of epsilon-aminocaproic acid and tranexamic acid is not
      associated with early baffle fenestration closure after the modified Fontan
      procedure. It is concluded that these agents can be used without increasing the
      risk of spontaneous baffle fenestration closure.

PMID- 10890477
TI  - The effect of heparin-coated pulmonary artery catheters on activated coagulation
      time in cardiac surgical patients.
AB  - OBJECTIVE: To investigate the effect of heparin-coated pulmonary artery catheters
      (HPACs) on activated coagulation time (ACT) drawn through a non-heparin-coated
      introducer sheath. DESIGN: A prospective, observational study. SETTING:
      University teaching hospital. PARTICIPANTS: Patients scheduled for surgical
      procedures requiring cardiopulmonary bypass. INTERVENTIONS: With institutional
      review board approval, 63 patients without prior coagulopathy undergoing
      procedures requiring cardiopulmonary bypass were studied. Jugular venous and
      radial arterial ACTs were measured before and immediately after insertion of an
      HPAC. Additional measurements were obtained 1 hour later and 4 minutes after
      completion of protamine infusion. MEASUREMENTS AND MAIN RESULTS: The ACT drawn
      from the introducer after placement of an HPAC was 48 seconds greater than the
      ACT drawn before the HPAC was placed (p < 0.0001). This difference was still
      present 1 hour later but not after the administration of protamine or in blood
      drawn at any time from another site. Baseline ACTs drawn from radial arterial
      catheters, kept patent using a heparin flush system, resulted in elevated
      measurements, despite withdrawing seven times the deadspace before taking a
      sample. CONCLUSIONS: Blood obtained from an introducer with an HPAC in situ
      provides a spuriously high ACT. ACTs drawn from catheters kept patent using
      heparin flush also result in prolonged measurements. Baseline ACT measurement
      from an introducer should be obtained before placement of the HPAC.

PMID- 10890478
TI  - Volume therapy with a new hydroxyethyl starch solution in cardiac surgical
      patients before cardiopulmonary bypass.
AB  - OBJECTIVE: To compare the hemodynamic efficacy of a new hydroxyethyl starch (HES)
      preparation (130/0.4) with an HES 200/0.5 solution. DESIGN: Prospective,
      randomized, double-blind, phase II study. SETTING: An urban, university
      affiliated hospital. PARTICIPANTS: Twenty patients undergoing elective first-time
      cardiac surgery. INTERVENTIONS: After induction of anesthesia and before the
      start of surgery, a new HES 130/0.4 (molecular weight, 130,000 d; degree of
      substitution, 0.4) (n = 10) or HES 200/0.5 (molecular weight, 200,000 d; degree
      of substitution, 0.5) (n = 10) was infused (10 mL/kg) within 30 minutes when
      pulmonary capillary wedge pressure was less than 10 mmHg. MEASUREMENTS AND MAIN
      RESULTS: Extensive hemodynamic monitoring was performed 30 and 60 minutes after
      the end of infusion. Then surgery was started. Standard laboratory parameters
      were measured before surgery and on the 1st postoperative day. A similar amount
      of HES was given in both groups (HES 130, 795+/-75 mL; HES 200, 820+/-90 mL).
      Filling pressures (central venous pressure, pulmonary capillary wedge pressure)
      and cardiac index increased similarly in both groups and remained significantly
      elevated 60 minutes after the end of infusion. All other hemodynamic parameters
      were similar between the two volume groups. Renal (creatinine) and hepatic
      function (aspartate aminotransferase, alanine aminotransferase) and hemostasis
      (platelet count, activated partial thromboplastin time, blood loss) were without
      group differences until the morning of the 1st postoperative day. CONCLUSIONS:
      The new 6% HES 130/0.4 was as effective as a 6% HES 200/0.5 preparation in regard
      to hemodynamic efficacy. No negative side effects on organ function were seen.
      The 6% HES 130/0.4 solution may become an alternative strategy for volume therapy
      in cardiac surgery.

PMID- 10890479
TI  - Perioperative blood pressure control: a prospective survey of patient management
      in cardiac surgery.
AB  - OBJECTIVE: To conduct a survey of current cardiac anesthetic practice in Europe
      and the United States, as a first step toward establishing guidelines for the
      management of perioperative hypertension. DESIGN: Prospective, multicenter study.
      SETTING: University hospitals. PARTICIPANTS: Unselected patients (n = 1,930)
      requiring cardiac surgery. INTERVENTIONS: Data extending from the preoperative
      evaluation to 120 hours or more after surgery were collected from all patients.
      MEASUREMENTS AND MAIN RESULTS: Only the data from patients undergoing coronary
      artery bypass surgery, valve surgery, or combined procedures were analyzed,
      leaving a final total of 1,660 patients from the original 1,930. Of these, 88%
      were treated at least once perioperatively to lower arterial blood pressure.
      Deepening of anesthesia was the most commonly used antihypertensive measure
      (68%), regardless of the ongoing anesthetic regimen, and was usually combined
      with vasodilator therapy, most frequently nitroglycerin (53%) or sodium
      nitroprusside (28%). Reported perioperative mean arterial pressure (MAP) was 15
      to 20 mmHg lower than MAP before anesthesia induction, regardless of the use of
      antihypertensive therapy. The MAP at which antihypertensive treatment was
      initiated varied markedly among the various phases of surgery and showed no clear
      correlation with preoperative MAP. CONCLUSIONS: The results of this survey show
      that current anesthetic practice tries to prevent perioperative hypertension
      wherever possible during cardiac surgery. Blood pressure measurements taken
      before surgery have little influence on the development of hypertension
      intraoperatively, and the main determinants of perioperative blood pressure
      control and the need for therapeutic intervention are factors arising from the
      surgical procedure itself, such as aortic cross-clamping and activation of
      adrenergic mechanisms.

PMID- 10890480
TI  - Femoral artery pressures are more reliable than radial artery pressures on
      initiation of cardiopulmonary bypass.
AB  - OBJECTIVE: To compare radial and femoral artery perfusion pressure during
      initiation and various stages of cardiopulmonary bypass (CPB). DESIGN:
      Prospective study. SETTING: The cardiac center of a tertiary referral teaching
      institute. PARTICIPANTS: Sixty consecutive patients of all ages undergoing a
      variety of cardiac operations. INTERVENTIONS: Radial and femoral arterial
      pressures were measured in all patients on the same transducer, from the
      beginning to end of CPB. MEASUREMENTS AND MAIN RESULTS: Mean perfusion pressures
      on CPB measured at the femoral artery at 1, 5, 10, and 15 minutes of CPB were
      38.4+/-3.6, 46.2+/-3.1, 49.7+/-3.9, and 52.8+/-4.1 mmHg and were significantly
      greater than the corresponding radial artery pressures (29.9+/-4.1, 35.3+/-6.1,
      40.9+/-4.8, and 41.8+/-5.3 mmHg) (p < 0.001). At 30 minutes and 60 minutes of
      CPB, femoral artery pressures are higher (60.3+/-8.8 mmHg and 66.4+/-8.2 mmHg)
      compared with radial artery pressures (54.7+/-6.9 mmHg and 59.6+/-6.1 mmHg), but
      the difference is less significant (p < 0.05). On conclusion of CPB, mean femoral
      artery pressures (70.9+/-6.7 mmHg) are greater than mean radial artery pressures
      (67.6+/-8.1 mmHg) (NS). CONCLUSIONS: Although radial artery pressures are more
      commonly monitored during cardiac surgery, femoral artery perfusion pressures are
      more reliable during the initial part of CPB, and routine monitoring of femoral
      artery pressures may prevent vasoconstrictor use on initiation of CPB.

PMID- 10890481
TI  - Transesophageal atrial pacing reduces phenylephrine needed for blood pressure
      support during carotid endarterectomy.
AB  - OBJECTIVE: To determine whether transesophageal atrial pacing reduces
      phenylephrine requirement for blood pressure support during general anesthesia
      for carotid endarterectomy. DESIGN: Prospective randomized clinical study.
      SETTING: University hospital. PARTICIPANTS: Thirty-six patients undergoing
      elective carotid endarterectomy under general anesthesia. INTERVENTIONS: Adults
      of either sex (n = 36) received general anesthesia using a standardized
      anesthetic regimen for elective carotid endarterectomy. Phenylephrine
      requirements were measured in patients having carotid endarterectomy and
      randomized to phenylephrine infusion (group 1, 19 patients) or phenylephrine
      infusion plus transesophageal atrial pacing (group 2, 17 patients) to maintain
      systolic blood pressure within +/-20% of baseline systolic blood pressure.
      MEASUREMENTS AND MAIN RESULTS: Measurements included (1) the amount of
      phenylephrine required in each group, (2) the variance of systolic blood pressure
      outside the desired range, and (3) the occurrence of postoperative
      electrocardiogram or myocardial enzyme changes suggesting myocardial ischemia.
      The average requirement for phenylephrine was less for group 2 (0.28+/-0.16
      microg/kg/min) than for group 1 patients (0.46+/-0.23 microg/kg/min) (p = 0.02 by
      t-test). CONCLUSIONS: Under controlled conditions of general anesthesia for
      carotid endarterectomy, transesophageal atrial pacing reduced by 40% the amount
      of phenylephrine needed for blood pressure support and helped in the treatment of
      disadvantageous sinus bradycardia.

PMID- 10890482
TI  - Influence of dopexamine on hemodynamics, intramucosal pH, and regulators of the
      macrocirculation and microcirculation in patients undergoing abdominal aortic
      surgery.
AB  - OBJECTIVE: To investigate whether dopexamine hydrochloride beneficially
      influences splanchnic perfusion and regulators of the macrocirculation and
      microcirculation in patients undergoing surgery of the abdominal aorta. DESIGN:
      Prospective, blinded, and randomized study. SETTING: University-affiliated
      hospital. PARTICIPANTS: Twenty patients undergoing elective abdominal aortic
      surgery. INTERVENTIONS: The patients were randomized to one of two groups. In the
      dopexamine group (DOP, n = 10), dopexamine, 1 microg/kg/min, was started before
      surgery and continued for 24 hours. In the control group (COG, n = 10), patients
      received saline solution as placebo. Extensive hemodynamic monitoring was carried
      out using a pulmonary artery catheter, and intramucosal pH was measured using a
      gastric tonometer. From arterial blood samples, important regulators of the
      circulation were measured before dopexamine was administered (T0), before aortic
      clamping (T1), 20 minutes after aortic clamping (T2), after declamping the first
      leg (T3), at the end of surgery (T4), 1 hour postoperatively (T5), and 24 hours
      postoperatively (T6). MEASUREMENTS AND MAIN RESULTS: Heart rate increased
      significantly in DOP (63+/-16 to 84+/-18 beats/min). At T5, mean pulmonary artery
      pressure was significantly lower in DOP (15+/-6 mmHg) than in COG (22+/-6 mmHg).
      During aortic clamping, pulmonary capillary wedge pressure increased
      significantly in both groups. Cardiac index increased significantly from baseline
      only in the dopexamine patients. No significant differences between the groups
      were seen with regard to oxygenation parameters and intramucosal pH. Renin plasma
      levels increased significantly only in COG (46+/-32 to 99+/-55 microU/mL).
      Endothelin and atrial natriuretic peptide plasma levels showed no significant
      differences between the two groups. Atrial natriuretic peptide increased
      significantly only in DOP (366+/-171 pg/mL; COG, 159+/-71 pg/mL). Antidiuretic
      hormone, norepinephrine, and epinephrine plasma levels increased significantly
      from baseline in both groups, without showing significant differences between the
      groups. CONCLUSIONS: In patients undergoing abdominal aortic surgery,
      prophylactic perioperative administration of dopexamine hydrochloride produced
      effects on hemodynamics but without improving oxygenation and intramucosal pH.
      From the measured regulators of the circulation, only renin was beneficially
      affected.

PMID- 10890483
TI  - The use of the 5-HT3-receptor antagonist ondansetron for the treatment of
      postcardiotomy delirium.
AB  - OBJECTIVE: To evaluate the effect of the 5-HT3-receptor antagonist ondansetron in
      patients with postcardiotomy delirium. DESIGN: Prospective study. SETTING:
      University hospital. PARTICIPANTS: Thirty-five patients who had undergone
      coronary artery bypass graft surgery. INTERVENTIONS: Thirty-five patients, 23 men
      and 12 women, who developed delirium in the intensive care unit after coronary
      artery bypass graft surgery were included. Mean patient age was 51.3 years
      (range, 36 to 79 years). A mental status scoring scale was developed, and
      patients were scored 0 to 4 according to their delirium status after confirming
      that there were no correctable metabolic abnormalities as an underlying cause for
      delirium. Normal behavior was scored as 0, and severe verbal and physical
      agitation was scored as 4. Patients received a single dose of ondansetron, 8 mg,
      intravenously and were reevaluated 10 minutes later. MEASUREMENTS AND MAIN
      RESULTS: Before the treatment, 7 patients had a score of 2 (20%); 10 patients
      (28.6%), 3; and 18 patients (51.4%), 4. After the treatment, 28 patients (80%)
      dropped their score to 0; 6 patients (17.1%) dropped to a score of 1, and 1
      patient (2.9%) remained at a score of 4. The mean score dropped from 3.20 + 1.01
      to 0.29 + 0.75 after treatment. Wilcoxon signed ranks test was used for
      statistical evaluation, and the fall in delirium score after ondansetron
      treatment was found to be statistically significant (p < 0.001). CONCLUSIONS: The
      use of ondansetron was effective and safe and without important side effects.
      This positive effect of the 5-HT3-receptor antagonist ondansetron led to
      speculation that impaired serotonin metabolism may play a role in postcardiotomy
      delirium.

PMID- 10890484
TI  - Pathogenesis, risk factors, and incidence of upper gastrointestinal bleeding
      after cardiac surgery: is specific prophylaxis in routine bypass procedures
      needed?
AB  - OBJECTIVES: (1) To obtain a literature review concerning pathogenesis and
      incidence of stress ulceration (SU) in patients undergoing cardiac surgery. (2)
      To determine which methods are useful in the prevention of SU and to analyze
      whether SU prophylaxis by acid reduction is effective in patients undergoing
      cardiac surgery. DESIGN: Literature review from Medline and reference list of
      identified articles until 1999. MEASUREMENTS AND MAIN RESULTS: SU and upper
      gastrointestinal bleeding (UGIB) in patients after cardiac surgery have been
      reported since 1957. All articles were retrospective reports. Definitions of SU
      and UGIB were variable. Ischemia, reperfusion injury, and endotoxemia were the
      main pathogenetic mechanisms in SU formation. Valve replacement, aortic cross
      clamping and bypass time, nonpulsatile flow during bypass, reoperation, and
      inflammatory state were risk factors for UGIB. Randomized, controlled clinical
      trials concerning SU prophylaxis have not been performed. The overall incidence
      of UGIB was 0.45% (638 bleeds in 141,887 patients). In patients with known use of
      SU prophylaxis with histamine2-receptor antagonists or antacids, the incidence of
      UGIB was 0.35%, and in patients without these medications, the incidence of UGIB
      was 0.45% (p = 0.16). CONCLUSIONS: Pathogenesis and risk factors for SU and UGIB
      are summarized. A review of the literature showed that the incidence of UGIB in
      patients after cardiac surgery was low. A randomized, controlled trial concerning
      pharmacologic stress ulcer prophylaxis has not been performed. The available
      retrospective reports concerning pharmacologic stress ulcer prophylaxis do not
      support the routine use of histamine2-receptor antagonists.

PMID- 10890485
TI  - Acute heparin-induced thrombocytopenia type II during cardiopulmonary bypass.

PMID- 10890486
TI  - Management of urgent high-risk cardiopulmonary bypass in patients with heparin
      induced thrombocytopenia type II and coexisting disorders of renal function: use
      of heparin and epoprostenol combined with on-line monitoring of platelet
      function.

PMID- 10890488
TI  - Spontaneous coronary artery dissection in a healthy 24-year-old woman.

PMID- 10890487
TI  - Uncomplicated heparinization for cardiopulmonary bypass in a patient with
      antiheparin antibodies.

PMID- 10890489
TI  - Hemodynamic deterioration after cardiopulmonary bypass during pregnancy:
      resuscitation by postoperative emergency Cesarean section.

PMID- 10890490
TI  - Anesthesia for left ventricular assist device placement.
AB  - Appropriate anesthesia for LVAD placement needs to incorporate an understanding
      of the surgical procedure and LVAD physiology, the altered physiology and
      pharmacology of the cardiac failure patient, and a knowledge of the interaction
      of anesthesia with the potent cardiac drugs used in end-stage heart failure
      therapy. The anesthesiologist is faced with a critically ill decompensated
      patient, often with altered renal and hepatic function, but must ensure adequate
      anesthesia to avoid intraoperative awareness. Intelligent use of TEE can assist
      the surgeon to pinpoint potential pitfalls of LVAD placement and can have a
      significant effect on improving outcome in these challenging patients.

PMID- 10890491
TI  - Case 3--2000. Improper administration of protamine during cardiopulmonary bypass.

PMID- 10890492
TI  - Case 4--2000. A systematic approach to intraoperative transesophageal
      echocardiographic evaluation of the mitral valve apparatus with anatomic
      correlation.

PMID- 10890493
TI  - Pro: Magnesium should be administered to all coronary artery bypass graft surgery
      patients undergoing cardiopulmonary bypass.

PMID- 10890494
TI  - Con: Magnesium should not be administered to all coronary artery bypass graft
      surgery patients undergoing cardiopulmonary bypass.

PMID- 10890495
TI  - An unexpected flow abnormality.

PMID- 10890496
TI  - Free-floating density.

PMID- 10890497
TI  - Intrathecal morphine for coronary artery bypass graft surgery revisited.

PMID- 10890498
TI  - Thoracic epidural anesthesia as an adjunct to general anesthesia for cardiac
      surgery: effects on ventilation-perfusion relationships.

PMID- 10890499
TI  - Coronary revascularization with the use of an axial flow pump and high-dose
      esmolol.

PMID- 10890500
TI  - Is an axial flow pump necessary during beating heart surgery?

PMID- 10890501
TI  - Interpretation of eustachian valve motion.

PMID- 10890502
TI  - Prediction of toxicity from chemical structure.
AB  - The basis for the prediction of toxicity from chemical structure is that the
      properties of a chemical are implicit in its molecular structure. Biological
      activity can be expressed as a function of partition and reactivity, that is, for
      a chemical to be able to express its toxicity, it must be transported from its
      site of administration to its site of action and then it must bind to or react
      with its receptor or target. This process may also involve metabolic
      transformation of the chemical. The application of these principles to the
      prediction of the toxicity of new or untested chemicals has been achieved in a
      number of different ways covering a wide range of complexity, from computer
      systems containing databases of hundreds of chemicals, to simple "reading across"
      between chemicals with similar chemical/toxicological functionality. The common
      feature of the approaches described in this article is that their starting point
      is a mechanistic hypothesis linking chemical structure and/or functionality with
      the toxicological endpoint of interest. The prediction of toxicity from chemical
      structure can make a valuable contribution to the reduction of animal usage in
      the screening out of potentially toxic chemicals at an early stage and in
      providing data for making positive classifications of toxicity.

PMID- 10890503
TI  - Effects of parasitism and pesticide exposure on characteristics and functions of
      hemocyte populations in the freshwater snail Lymnaea palustris (Gastropoda,
      Pulmonata).
AB  - Morphological characteristics and functions of hemocytes were used to compare the
      immunological effects of biological and chemical stress in the freshwater snail
      Lymnaea palustris. Animals were either infected by a trematode parasite
      (Metaleptocephalus sp.), or exposed to environmental contaminants, namely
      atrazine and hexachlorobenzene (HCB). Three populations of circulating hemocytes,
      morphologically and cytochemically distinct (round cells, hyalinocytes,
      granulocytes), were identified in both control and parasitized or pesticide
      exposed snails. After 6 h of exposure, HCB and atrazine resulted in 8-fold
      increases in the mean total number of hemocytes, whereas only a 2.2-fold increase
      was observed 6 h after cercaria emission in parasitized snails. The impact of HCB
      was limited to the first 24 h of exposure, whereas long-lasting effects of
      atrazine were observed. Hyalinocytes and, to a lesser extent, round cells
      contributed most to the increases in hemocyte density in pesticide-exposed
      snails. Parasitism and atrazine treatment resulted in significant increases of
      lectin-stained hemocytes, whereas exposure to HCB did not affect the percentages
      of stained and unstained cells. Hemocyte phagocytic activity increased in HCB
      exposed snails but with no concomitant change of the oxidative burst. Opposite
      results were obtained in atrazine-treated snail hemocytes, with unchanged
      phagocytosis and decreased phorbol 12-myristate 13-acetate-stimulated production
      of reactive oxygen intermediates. No increase in phagocytosis, or in the
      production of reactive oxygen intermediates, was observed in hemocytes from
      parasitized snails. Infection with the immunologically compatible trematode
      parasite Metaleptocephalus sp. and exposure to atrazine generated similar
      reactions from circulating hemocytes, whereas a different response pattern was
      observed in HCB-exposed snails.

PMID- 10890504
TI  - Toxicity of the heterocyclic amine batracylin: investigation of rodent N
      acetyltransferase activity and potential contribution of cytochrome P450 3A.
AB  - The heterocyclic amine, batracylin (BAT), is genotoxic and several lines of
      evidence suggest that acetylation is one step in the formation of a DNA-damaging
      product. The variation in susceptibility to BAT toxicity observed between rats
      and mice has also been linked to the acetylated product. BAT N-acetyltransferase
      (NAT) activity was determined in rat and mouse hepatic cytosols. Formation of
      acetylbatracylin (ABAT) was 6 times greater in F-344 hepatic samples compared to
      either mouse strain, while hepatic BAT NAT activities were similar in C57B1/6 and
      A/J mice. No deacetylation of ABAT was detected. In contrast, 2-aminofluorene NAT
      activity in C57B1/6 hepatic cytosol was twice that of the A/J strain and
      activities in both strains of mice were greater than in rat. Deacetylation of 2
      acetylaminofluorene was detected in both species with enzyme activities in
      C57B1/6>A/J>F-344. Hepatocytes from the F-344 rats, the species most sensitive to
      BAT toxicity, were used to investigate the contribution of other
      biotransformation reactions to BAT cytotoxicity. Leakage of cellular lactate
      dehydrogenase was greater in hepatocytes from male rats than from females,
      increased on in vivo exposure to dexamethasone, and decreased in the presence of
      troleandomycin, suggesting that CYP3A-mediated biotransformation of BAT is
      involved in the formation of a cytotoxic product. When phenol red, a substrate
      for UDP-glucuronsyltransferase (UDPGT), was absent from the medium, BAT
      cytotoxicity was reduced. These data are consistent with a role for NAT, CYP, and
      UDPGT in the biotransformation of BAT.

PMID- 10890505
TI  - Hydroquinone inhibits PMA-induced activation of NFkappaB in primary human CD19+ B
      lymphocytes.
AB  - Hydroquinone (HQ), a reactive metabolite of benzene, is known to inhibit mitogen
      stimulated activation of both T and B lymphocytes. Despite extensive study, the
      underlying mechanism for the immunotoxicity of the HQ is not clear. We have
      previously demonstrated that 1 micromol/L HQ inhibits TNF-induced activation of
      NFkappaB in CD4+ T cells, resulting in decreased IL-2 production. NFkappaB, known
      to be important in T lymphocytes, also plays a critical role in normal B cell
      development and activation. We therefore hypothesized that alterations in
      NFkappaB might be involved in HQ-induced B cell immunosuppression as well. In
      this study, we demonstrate that 1-10 micromol/L HQ inhibits PMA/ionomycin-induced
      activation of NFkappaB in primary human CD19+ B cells. Inhibition of NFkappaB is
      accompanied by a dose-dependent decrease in PMA-stimulated production of TNF with
      no corresponding loss in viability or increased apoptosis. HQ also does not
      appear to alter NFkappaB directly, as preincubation of B cell nuclear extracts
      with HQ does not diminish DNA binding activity of this protein. In contrast to T
      cells, inhibition of NFkappaB by HQ in B cells is not reversible after 72 h in
      culture, suggesting a long-term functional suppression. These data support our
      original findings in T cells and indicate that NFkappaB is particularly
      susceptible to inhibition by HQ. We further hypothesize that inhibition of
      NFkappaB in lymphocytes, and perhaps other cell types as well, may play a
      significant role in the observed toxicity of HQ.

PMID- 10890506
TI  - Apoptosis evaluation in epithelial cells exposed to different chemicals:
      relevance of floating cells.
AB  - The recent increase in understanding of cell death has promoted new approaches in
      toxicological studies, mainly those dealing with in vitro systems where the
      evaluation of cell death has been the most widely adopted end-point in measuring
      the effects of chemical toxicants. The aim of this study was to investigate the
      possibility of improving the traditional cytotoxicity test protocols in order to
      produce more specific information on the type of cell death induced by exposure
      to toxicants. In particular, we characterized the mode of cell death in an
      established epithelial cell line, HEp-2 cells, which is frequently used in
      cytotoxicity testing owing to its easy handling and standardization of culture
      conditions. Reference chemicals for apoptosis and necrosis were selected as
      controls, together with other molecules that have been shown, in preliminary
      studies, to induce various morphological and structural modifications in relation
      to cell death. The results obtained show that: (a) the floating fraction of
      treated cells gives the clearest picture of the necrotic/apoptotic distribution;
      (b) morphological analysis is crucial for characterization of apoptosis; (c) more
      than one cytotoxic end-point is necessary to clearly identify the type of cell
      death.

PMID- 10890507
TI  - Establishment and characterization of equine autonomic ganglion cell lines to
      enable direct testing of candidate toxins involved in equine dysautonomia (grass
      sickness).
AB  - To enable direct testing of a range of potential toxins or pathogens that might
      be involved in grass sickness, equine thoracic sympathetic chain ganglion cell
      lines were established from primary cell cultures by retroviral-mediated
      transduction of the temperature-sensitive mutant of the establishment oncogene
      encoding SV40 large T antigen. Morphological and behavioral features, temperature
      dependence, and immunocytochemical characteristics of the cell lines were
      investigated. The majority of cells were noradrenergic neurons in which dopamine
      beta-hydroxylase, the enzyme that catalyzes norepinephrine synthesis, and
      neuropeptide Y coexisted. Cells treated with plasma from grass sickness cases
      that had previously been shown to induce autonomic nervous system damage when
      injected into normal horses showed significantly decreased mitochondrial function
      after 1 day. After 3 days exposure most cells showed severe degeneration in
      contrast to those treated with normal plasma. Liver and lung cell lines were also
      susceptible to plasma, suggesting that the toxin is not specifically neurotoxic.

PMID- 10890508
TI  - Sample preparation for the analysis of flavors and off-flavors in foods.
AB  - Off-flavors in foods may originate from environmental pollutants, the growth of
      microorganisms, oxidation of lipids, or endogenous enzymatic decomposition in the
      foods. The chromatographic analysis of flavors and off-flavors in foods usually
      requires that the samples first be processed to remove as many interfering
      compounds as possible. For analysis of foods by gas chromatography (GC), sample
      preparation may include mincing, homogenation, centrifugation, distillation,
      simple solvent extraction, supercritical fluid extraction, pressurized-fluid
      extraction, microwave-assisted extraction, Soxhlet extraction, or methylation.
      For high-performance liquid chromatography of amines in fish, cheese, sausage and
      olive oil or aldehydes in fruit juice, sample preparation may include solvent
      extraction and derivatization. Headspace GC analysis of orange juice, fish,
      dehydrated potatoes, and milk requires almost no sample preparation. Purge-and
      trap GC analysis of dairy products, seafoods, and garlic may require heating,
      microwave-mediated distillation, purging the sample with inert gases and trapping
      the analytes with Tenax or C18, thermal desorption, cryofocusing, or elution with
      ethyl acetate. Solid-phase microextraction GC analysis of spices, milk and fish
      can involve microwave-mediated distillation, and usually requires adsorption on
      poly(dimethyl)siloxane or electrodeposition on fibers followed by thermal
      desorption. For short-path thermal desorption GC analysis of spices, herbs,
      coffee, peanuts, candy, mushrooms, beverages, olive oil, honey, and milk, samples
      are placed in a glass-lined stainless steel thermal desorption tube, which is
      purged with helium and then heated gradually to desorb the volatiles for
      analysis. Few of the methods that are available for analysis of food flavors and
      off-flavors can be described simultaneously as cheap, easy and good.

PMID- 10890509
TI  - Applications of solid-phase microextraction in food analysis.
AB  - Food analysis is important for the evaluation of the nutritional value and
      quality of fresh and processed products, and for monitoring food additives and
      other toxic contaminants. Sample preparation, such as extraction, concentration
      and isolation of analytes, greatly influences the reliable and accurate analysis
      of food. Solid-phase microextraction (SPME) is a new sample preparation technique
      using a fused-silica fiber that is coated on the outside with an appropriate
      stationary phase. Analyte in the sample is directly extracted to the fiber
      coating. The SPME technique can be used routinely in combination with gas
      chromatography (GC), GC-mass spectrometry (GC-MS), high-performance liquid
      chromatography (HPLC) or LC-MS. Furthermore, another SPME technique known as in
      tube SPME has also been developed for combination with LC or LC-MS using an open
      tubular fused-silica capillary column as an SPME device instead of SPME fiber.
      These methods using SPME techniques save preparation time, solvent purchase and
      disposal costs, and can improve the detection limits. This review summarizes the
      SPME techniques for coupling with various analytical instruments and the
      applications of these techniques to food analysis.

PMID- 10890510
TI  - Applications of matrix solid-phase dispersion in food analysis.
AB  - Matrix solid-phase dispersion (MSPD), a patented process for the simultaneous
      disruption and extraction of solid and semi-solid samples, was first reported in
      1989. Since that time, MSPD has found application in numerous fields, but has
      proven to be particularly applicable for the analysis of drugs, pollutants,
      pesticides and other components in foods. The present article provides a review
      of these and related applications and discusses both the practical and
      theoretical aspects for the use of MSPD in sample processing.

PMID- 10890511
TI  - Beta2-agonist extraction procedures for chromatographic analysis.
AB  - Normally, different procedures were necessary to prepare sample matrices for
      chromatographic determination of beta2-agonists. The present review includes
      sampling, pre-treatment and extraction/purification for urine, plasma, liver,
      meat, feeds, hair and milk powder, as previous steps for chromatographic analysis
      of beta2-agonists. Six methodologies were especially revised for
      extraction/purification namely, liquid-liquid extraction, solid-phase extraction
      (SPE), matrix solid-phase dispersion, immunoaffinity chromatography, dialysis and
      supercritical fluid extraction. SPE was discussed in detail and five mechanisms
      were described: adsorption, apolar, polar, ion-exchange and mixed phase. A brief
      conclusion in this field was also outlined.

PMID- 10890512
TI  - Application of ion-exchange cartridge clean-up in food analysis III.
      Determination of benzylpenicillin, phenoxymethyl-penicillin, oxacillin,
      cloxacillin, nafcillin and dicloxacillin in bovine liver and kidney by liquid
      chromatography with ultraviolet detection.
AB  - A multiresidue analytical method was developed for the simultaneous determination
      of benzylpenicillin (PCG), phenoxymethylpenicillin (PCV), oxacillin (MPIPC),
      cloxacillin (MCIPC), nafcillin (NFPC) and dicloxacillin (MDIPC) in bovine liver
      and kidney. The method involves the use of an ion-exchange cartridge for sample
      clean-up followed by ion-pair high-performance liquid chromatography with
      ultraviolet detection. The recoveries of PCG, PCV, MPIPC, MCIPC, NFPC and MDIPC
      from bovine liver spiked at levels of 0.5 mg/kg and 0.1 mg/kg were in the range
      of 73-91% and 83-96% with coefficients of variation of 1.4-4.2% and 3.4-8.7%,
      respectively. For bovine kidney spiked at levels of 0.5 mg/kg and 0.1 mg/kg, the
      recoveries of these compounds were 79-92% and 82-92% with RSDs of 1.8-5.9% and
      2.7-7.8%, respectively. The detection limits for the six penicillins were 0.02
      0.05 mg/kg in bovine liver and kidney.

PMID- 10890513
TI  - Headspace solid-phase microextraction method for determining 3-alkyl-2
      methoxypyrazines in musts by means of polydimethylsiloxane-divinylbenzene fibres.
AB  - A method for determining 2-methoxypyrazine, 3-methyl-, 3-ethyl-, 3-isopropyl-, 3
      sec.-butyl- and 3-isobutyl-2-methoxypyrazine in musts is described. It involves
      headspace solid-phase microextraction (SPME) and determination by capillary gas
      chromatography using nitrogen-phosphorous detection. Pyrazines were
      satisfactorily separated under isothermal conditions, and quantification was
      carried out using 3-isopropyl-2-ethoxypyrazine as the internal standard. Ionic
      strength, time and temperature were studied in order to make SPME as efficient as
      possible. The developed method enabled detection limits at the 0.1 ng(-1) levels
      for some of the analytes. The method was successfully applied to identify and
      quantify different 3-alkyl-2-methoxypyrazines in experimental musts of Cabernet
      Sauvignon and Merlot. Their evolution during the ripening was also monitored.

PMID- 10890514
TI  - Comparison of different commercial solid-phase extraction cartridges used to
      extract heterocyclic amines from a lyophilised meat extract.
AB  - Heterocyclic amines are a group of potent mutagenic compounds which are generated
      when muscle meat is cooked. Since they are possible human carcinogens, these
      mutagens have received considerable attention in recent years, and several
      analytical techniques have been developed for their quantification. Although the
      purification step is one of the most important, there are a great number of
      variables influencing the recovery of the amines, especially when real samples
      are analysed. In this work we studied the influence of sample spiking mode on the
      recoveries. Furthermore, on the basis of a previously developed clean-up method,
      the effect of changing commercial source and structure of the sorbents used in
      two solid-phase extraction steps was examined. This purification method was
      applied to the quantification of the heterocyclic aromatic amines present in a
      lyophilised meat extract by means of liquid chromatography-mass spectrometry.

PMID- 10890515
TI  - Determination of 1-nitropyrene in herbs after selective enrichment by a sol-gel
      generated immunoaffinity column.
AB  - Using the determination of 1-nitropyrene as an example the paper demonstrates the
      advantages of including a highly selective sol-gel-generated immunoaffinity
      column in the sequence of clean-up steps necessary to determine haptens in
      complex matrices. The sol-gel method to immobilise antibodies enlarges the
      variety of immunoaffinity columns available and leads to mechanically stable
      columns with constant retention characteristics. The sample preparation scheme
      proposed combines acetonitrile extraction, size-exclusion and immunoaffinity
      chromatography. 1-Nitropyrene is then separated by reversed-phase HPLC from
      interfering compounds and determined after catalytic on-line reduction to the
      corresponding amine by spectrofluorimetry. Concentrations in the range from 0.1
      to 1.4 microg/kg 1-nitropyrene were detected in herbs.

PMID- 10890516
TI  - Determination of fenpyroximate in apples by supercritical fluid extraction and
      packed capillary liquid chromatography with UV detection.
AB  - A method using off-line supercritical fluid extraction (SFE) and micro liquid
      chromatography (microLC) with UV detection at 260 nm, was developed for selective
      determination of fenpyroximate in apple samples. The packed capillary liquid
      chromatography method utilises 20 microl injection volumes with on-column
      focusing. A 350x0.32 mm capillary column packed with Kromasil 100-C18 of 5 microm
      particle size was used with a mobile phase of acetonitrile-10 mM ammonium acetate
      (85:15, v/v) at a flow of 5 microl/min. A two-step SFE procedure was used to
      extract fenpyroximate selectively in 2 g apple samples, with Hydromatrix (HMX)
      added as a water absorbent at a 1:1 (w:w) ratio. Fenpyroximate was extracted at
      200 bar and 90 degrees C for 15 min using carbon dioxide at a flow of 2 ml/min,
      and solvent trapping collection in 10 ml acetonitrile. The volume of the
      acetonitrile extract was reduced by evaporation and water was added to a final
      composition of acetonitrile-water (40:60, v/v). The resulting 2.0 ml solution was
      filtered using a 0.45 microm poly(vinylidene difluoride) syringe filter before
      microLC analysis. Validation of the method was accomplished with apple samples
      spiked with fenpyroximate, covering the range of 0.1 to 1.0 microg/kg. The within
      day and between-day repeatabilities were in the range 4-18% relative standard
      deviation. Accuracy, measured as recovery, was found to be approximately 60%.
      Apple samples from a field treated with fenpyroximate were analysed. None of the
      samples contained fenpyroximate above the quantification level.

PMID- 10890517
TI  - Thin-layer chromatography in food and agricultural analysis.
AB  - The TLC analysis of agricultural products, foods, beverages, and plant
      constituents is reviewed for the period from mid-1995 to mid-1999. Techniques and
      applications for a wide range of analyte and sample matrix types are covered,
      with specification of the particular layers, mobile phases, detection methods,
      and quantification conditions in many cases.

PMID- 10890518
TI  - Direct analysis of food samples by high-performance liquid chromatography.
AB  - A short review on the sample analysis of food samples by high-performance liquid
      chromatography is presented. The paper is focused on direct injection of liquid
      samples, automated solid-phase extraction and column switching techniques, on
      line dialysis and application of restricted-access media.

PMID- 10890519
TI  - Perfusion chromatography: an emergent technique for the analysis of food
      proteins.
AB  - Perfusion chromatography is a technique arised to overcome the problem associated
      with mass transfer in the separation of large molecules such as proteins by high
      performance liquid chromatography (HPLC). Perfusion media are constituted by two
      set of pores: throughpores (6000-8000 A) and diffusive pores (800-1500 A) which
      enable better access of macromolecules to the inner of the particle by the
      combination of convective and diffusive flow. As a consequence, times required
      for a chromatographic separation are reduced. Perfusion media are available in
      different chromatographic modes: reversed-phase, ion-exchange, hydrophobic
      interaction, and affinity. From the theoretical models developed to explain the
      dynamic of retention of solutes in perfusive supports, it was derived that
      efficiency of a separation was independent of the flow-rate and only depended
      slightly on the particle diameter. Furthermore, loading capacity was also
      independent of the superficial velocity. All these advantages have promoted the
      use of this chromatographic technique for the separation of biomolecules both in
      analytical and preparative chromatography. Characteristics of perfusion
      chromatography make this technique very interesting for the analysis of food
      proteins. Perfusion chromatography enables the assessment of protein composition
      of a foodstuff at sufficient speed and low cost to be suitable in routine
      analysis.

PMID- 10890520
TI  - C30 stationary phases for the analysis of food by liquid chromatography.
AB  - The introduction of a polymeric C30 liquid chromatographic column by Sander et
      al. [Anal. Chem., 66 (1994) 1667] designed for the separation of carotenoid
      isomers, has led to the development of improved analytical methods for these
      compounds. Subsequent commercial availability of polymerically bonded C30 columns
      has facilitated these advances, and applications to a wide variety of separation
      problems with biological samples have been described. This report provides a
      comprehensive review of applications of polymeric C30 columns, utilized in the
      determination of carotenoids, retinoids, and other nutrients and related
      compounds in complex, natural-matrix samples.

PMID- 10890521
TI  - On-line identification of phytochemical constituents in botanical extracts by
      combined high-performance liquid chromatographic-diode array detection-mass
      spectrometric techniques.
AB  - It is necessary to determine all of the phytochemical constituents of botanical
      extracts in order to ensure the reliability and repeatability of pharmacological
      and clinical research, to understand their bioactivities and possible side
      effects of active compounds and to enhance product quality control. HPLC
      chromatographic fingerprints can be applied for this kind of documentation.
      Combined HPLC-diode array detection-MS techniques can provide on-line UV and MS
      information for each peak in a chromatogram. In most cases, direct identification
      of the peaks is possible, based on comparison with published data or with
      standard compounds. This review will primarily focus on electrospray and
      thermospray ionization MS and their applications for the qualitative analyses of
      phenolic compounds, saponins, alkaloids and other classes of natural products in
      botanical extracts. Twenty-one of the most commonly used herbal examples, their
      phytochemical analyses and characteristics of their mass spectra are described.

PMID- 10890522
TI  - Determination of aldehydes in food by high-performance liquid chromatography with
      biosensor coupling and micromembrane suppressors.
AB  - A high-performance liquid chromatography system for the determination of
      aldehydes in food was developed incorporating an Cation MicroMembrane Suppressor
      (CMMS) and enzyme reactors packed with VA-Epoxy on which aldehyde dehydrogenase
      from bakers yeast and NADH oxidase from Bacillus licheniformis were immobilized.
      The method was based on the principle that the separation efficiency of HPLC is
      combined with the sensitivity of electrochemical detection and the specificity of
      enzymes. Main attention was directed to the determination of 5-hydroxymethyl-2
      furaldehyde and 2-furaldehyde, the occurrence of which is an indication of
      quality deterioration in several food products. The efficiency of the method has
      been shown by the analysis of honey, coffee and related beverages, refreshments,
      sherry, port, dry fruits and breakfast cereals.

PMID- 10890523
TI  - Electrophoretic methods in the analysis of beverages.
AB  - A review of the applications of electrophoresis to the determination of various
      compounds in beverage samples, namely beer, hard drinks, juice, milk, soft
      drinks, tea and wine, is presented.

PMID- 10890524
TI  - Herbicide and plant growth regulator analysis by capillary electrophoresis.
AB  - Capillary electrophoresis (CE) is a relatively new analytical technique that is
      just beginning to be employed in the area of pesticide residue analysis. With the
      development of more sensitive detectors and in conjunction with CE separation
      powers, it should be a well accepted technique for pesticide residue analysis in
      the future. This review describes CE methods that have been developed to analyze
      herbicides and grow regulators in water, soil and food.

PMID- 10890525
TI  - Applications of in-capillary reaction micellar electrokinetic chromatography in
      the food industry.
AB  - This review describes the quantitative analysis of in-capillary reactions by
      using capillary electrophoresis (CE) in the food industry. An electrophoretic
      analysis of products of an enzyme reaction of a substrate by in-capillary
      reaction was useful for the activity measurement of glucoamylase in sake rice
      koji. p-Nitrophenyl-beta-D-maltoside was employed as a substrate and p
      nitrophenyl-beta-D-glucopyranoside was the product of the enzyme reaction. The
      glucoamylase activity of sake rice koji samples gave a good linear relationship
      with the peak area observed in the in-capillary enzyme reaction method. Also, in
      capillary micellar electrokinetic chromatography (MEKC) was used for analyzing
      the Monascus pigment-mediated degradation of mutagenic 3-hydroxyamino-1-methyl-5H
      pyrido[4,3-b]indole. During the electrophoresis, the mutagen and the pigment, due
      to their different migration velocities, mix for a certain period of time to
      interact, and then they are separated and quantitated. The in-capillary reaction
      MEKC method can be applied to the routine quality control of enzyme activities in
      the food industry and the evaluation of mutagenic compounds in food materials.

PMID- 10890526
TI  - Substitution of fish species detected by thin-layer isoelectric focusing and a
      computer-assisted method for the evaluation of gels.
AB  - Fourteen fish species susceptible to substitution were analysed by the thin-layer
      isoelectric focusing technique on polyacrylamide gels of pH 3.5-9.5. Four fish
      per species were run on the same gel to verify the possibility to differentiate
      them according to their protein banding patterns. The occurrence of intraspecific
      differences due either to electrophoretic variations or to protein polymorphism
      was also observed. In fact, some of them showed few dissimilarities among their
      protein profiles. However, the differentiation was possible for all species, even
      for those belonging to the same order, family and genus. Computer-based tools
      combined with statistical analysis were implemented and usefully applied to avoid
      a subjective evaluation of the isoelectric focusing gels, and to verify the
      reliability of the preliminary visual comparison of protein patterns.

PMID- 10890527
TI  - Analysis of natural food pigments by capillary electrophoresis.
AB  - Lac, cochineal, safflower, gardenia, Monascus and elderberry pigments are used as
      food color additives in Japan. These natural pigments can be analyzed by
      capillary electrophoresis (CE). CE has several advantages over thin layer
      chromatography, gas chromatography and high-performance liquid chromatography,
      such as low capillary cost, reduced operating costs, small sample amounts, low
      production of waste materials and short analysis time. CE is shown to be a useful
      technique for the analysis of these natural food pigments and the pigments
      extracted from commercial food samples by solid-phase extraction method.

PMID- 10890528
TI  - MAP kinase pathways: molecular plug-and-play chips for the cell.
AB  - Mitogen-activated protein kinase (MAPK) pathways transduce a large variety of
      external signals in mammals, unicellular eukaryotes, and plants. In recent years,
      plant MAPK pathways have attracted increasing interest resulting in the isolation
      of a large number of different components. Studies on the function of these
      components have revealed that MAPKs play important roles in the response to a
      broad variety of stresses, but also in the signaling of plant hormones and the
      cell cycle. Besides giving an update on recent results, the success and logic of
      MAPK-based signal transduction cascades is discussed.

PMID- 10890529
TI  - A rapid induction by elicitors of the mRNA encoding CCD-1, a 14kDa Ca2+ -binding
      protein in wheat cultured cells.
AB  - Intracellular Ca(2+) has been implicated in the signal transduction processes
      during the development of the plant defense system against fungal pathogens. From
      wheat cultured cells that had been treated with the elicitor derived from Typhula
      ishikariensis, the ccd-1 gene encoding a 14 kDa Ca(2+)-binding protein with an
      acidic amphiphilic feature was isolated. The ccd-1-encoded protein (CCD-1) shares
      homology to the C-terminal half domain of centrin, a Ca(2+)-binding protein
      conserved in eukaryotes. Unlike typical eukaryotic centrins, CCD-1 contains only
      one Ca(2+)-binding loop, which corresponds to the one in the fourth EF-hand from
      the N-terminus of centrin. The recombinant CCD protein expressed in Escherichia
      coli bound to a phenyl-Sepharose column in the presence of Ca(2+) and was eluted
      out by EGTA. It also showed a Ca(2+)-dependent electrophoretic mobility shift on
      the non-denaturing polyacrylamide gel. The ccd-1 mRNA expression was rapidly
      induced by treatment with fungal and chitosan oligosaccharide elicitors, implying
      that it might have a role in transducing Ca(2+) signals provoked by the
      elicitors. The expression of the ccd-1 mRNA was induced by treatment with A23187,
      and the induction was suppressed by La(3+) or 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA). This study suggests the involvement of
      intracellular Ca(2+) in the elicitor-induced mRNA expression of a novel class of
      Ca(2+)-binding proteins conserved in higher plants.

PMID- 10890530
TI  - pGreen: a versatile and flexible binary Ti vector for Agrobacterium-mediated
      plant transformation.
AB  - Binary Ti vectors are the plasmid vectors of choice in Agrobacterium-mediated
      plant transformation protocols. The pGreen series of binary Ti vectors are
      configured for ease-of-use and to meet the demands of a wide range of
      transformation procedures for many plant species. This plasmid system allows any
      arrangement of selectable marker and reporter gene at the right and left T-DNA
      borders without compromising the choice of restriction sites for cloning, since
      the pGreen cloning sites are based on the well-known pBluescript general vector
      plasmids. Its size and copy number in Escherichia coli offers increased
      efficiencies in routine in vitro recombination procedures. pGreen can replicate
      in Agrobacterium only if another plasmid, pSoup, is co-resident in the same
      strain. pSoup provides replication functions in trans for pGreen. The removal of
      RepA and Mob functions has enabled the size of pGreen to be kept to a minimum.
      Versions of pGreen have been used to transform several plant species with the
      same efficiencies as other binary Ti vectors. Information on the pGreen plasmid
      system is supplemented by an Internet site (http://www.pgreen.ac.uk) through
      which comprehensive information, protocols, order forms and lists of different
      pGreen marker gene permutations can be found.

PMID- 10890531
TI  - Abscisic acid biosynthesis in tomato: regulation of zeaxanthin epoxidase and 9
      cis-epoxycarotenoid dioxygenase mRNAs by light/dark cycles, water stress and
      abscisic acid.
AB  - Two genes encoding enzymes in the abscisic acid (ABA) biosynthesis pathway,
      zeaxanthin epoxidase (ZEP) and 9-cis-epoxycarotenoid dioxygenase (NCED), have
      previously been cloned by transposon tagging in Nicotiana plumbaginifolia and
      maize respectively. We demonstrate that antisense down-regulation of the tomato
      gene LeZEP1 causes accumulation of zeaxanthin in leaves, suggesting that this
      gene also encodes ZEP. LeNCED1 is known to encode NCED from characterization of a
      null mutation (notabilis) in tomato. We have used LeZEP1 and LeNCED1 as probes to
      study gene expression in leaves and roots of whole plants given drought
      treatments, during light/dark cycles, and during dehydration of detached leaves.
      During drought stress, NCED mRNA increased in both leaves and roots, whereas ZEP
      mRNA increased in roots but not leaves. When detached leaves were dehydrated,
      NCED mRNA responded rapidly to small reductions in water content. Using a
      detached leaf system with ABA-deficient mutants and ABA feeding, we investigated
      the possibility that NCED mRNA is regulated by the end product of the pathway,
      ABA, but found no evidence that this is the case. We also describe strong diurnal
      expression patterns for both ZEP and NCED, with the two genes displaying
      distinctly different patterns. ZEP mRNA oscillated with a phase very similar to
      light-harvesting complex II (LHCII) mRNA, and oscillations continued in a 48 h
      dark period. NCED mRNA oscillated with a different phase and remained low during
      a 48 h dark period. Implications for regulation of water stress-induced ABA
      biosynthesis are discussed.

PMID- 10890532
TI  - Effect of pollination and exogenous ethylene on accumulation of ETR1 homologue
      transcripts during flower petal abscission in geranium (Pelargonium x hortorum
      L.H. Bailey).
AB  - We have isolated two cDNAs from geranium, PhETR1 and PhETR2. The deduced amino
      acid sequences of PhETR1 anti PhETR2 share 78% and 79% identity with ETR1 from
      Arabidopsis thaliana respectively. These genes are members of a multigene family
      and are expressed at moderate levels in leaves, pedicels, sepals, pistils and
      petals, and at very low levels in roots. PhETR1 and PhETR2 mRNAs are expressed in
      geranium florets long before they are receptive to pollination and transcript
      levels remain constant throughout floral development. Message levels of PhETR1
      and PhETR2 in pistils and receptacles are unaffected by self-pollination or
      treatment with 1 micro/l ethylene that induces petal abscission. Our results
      indicate that the amount of PhETR1 and PHETR2 mRNA is not indicative of the level
      of sensitivity of geranium florets to ethylene.

PMID- 10890533
TI  - Isolation of genes predominantly expressed in guard cells and epidermal cells of
      Nicotiana glauca.
AB  - Guard cells are specialized and metabolically active cells which arise during the
      differentiation of the epidermis. Using Nicotiana glauca epidermal peels as a
      source of purified guard cells, we have constructed a cDNA library from guard
      cell RNA. In order to isolate genes that are predominantly expressed in guard
      cells, we performed a differential screen of this library, comparing the
      hybridization of a radiolabeled cDNA probe synthesized from guard cell RNA to
      that from a mesophyll cell cDNA probe. Sixteen clones were isolated based on
      their greater level of hybridization with the guard cell probe. Of these, eight
      had high homology to lipid transfer protein (LTP), two were similar to glycine
      rich protein (GRP), and one displayed high homology to proline-rich proteins from
      Arabidopsis thaliana (AtPRP2, AtPRP4) and from potato guard cells (GPP). Northern
      analysis confirmed that one or more NgLTP genes, NgGRP1, and NgGPP1 are all
      differentially expressed, with highest levels in guard cells, and low or
      undetectable levels in mesophyll cells and in roots. In addition, all are induced
      to some degree in drought-stressed guard cells. NgLTP and NgGRP1 expression was
      localized by in situ hybridization to the guard cells and pavement cells in the
      epidermis. NgGRP1 expression was also detected in cells of the vasculature.
      Genomic Southern analysis indicated that LTP is encoded by a family of highly
      similar genes in N. glauca. This work has identified members of a subset of
      epidermis- and guard cell-predominant genes, whose protein products are likely to
      contribute to the unique properties acquired by guard cells and pavement cells
      during differentiation.

PMID- 10890535
TI  - Flower-predominant expression of a gene encoding a novel class I chitinase in
      rice (Oryza sativa L.).
AB  - A flower-predominant cDNA for a gene, termed OsChia 1;175, was isolated from a
      cDNA library of rice pistils. Northern blot and RT-PCR analyses revealed that the
      OsChia 1;175 gene is highly expressed in floral organs (pistils, stamens and
      lodicules at the heading stage) but not or at an extremely low level in
      vegetative organs. OsChia 1;175 encodes a protein that consists of 340 amino acid
      residues, and the putative mature protein shows 52% to 63% amino acid identity to
      class I chitinases of rice or other plants. The phylogenetic tree shows that the
      OsChia 1;175 protein is a new type of plant class I chitinase in rice. The
      expression of OsChia 1;175 in vegetative organs is not induced by several
      chemicals, UV, and wounding. The soluble putative mature OsChia 1;175 protein
      expressed in Escherichia coli exhibited chitinase activity in the assay with
      colloidal chitin as a substrate. Genomic Southern analysis revealed that the
      OsChia 1;175 gene was organized as a low-copy gene family. The rice genomic
      library was screened and a genome clone corresponding to OsChia 1;175 was
      isolated. The transcription start sites of the OsChia 1;175 gene were mapped by
      primer extension analysis. The 1.2 kb putative promoter region of the OsChia
      1;175 gene was fused to the GUS (beta-glucuronidase) gene, and this chimeric gene
      was introduced to rice by Agrobacterium-mediated transformation. The flower
      predominant gene expression was identified also in the transgenic rice plants.
      The high promoter activity was detected in the stigmas, styles, stamens and
      lodicules in transgenic plants. The possible functions of OsChia 1;175 are
      discussed.

PMID- 10890534
TI  - Direct evidence for ribonucleolytic activity of a PR-10-like protein from white
      lupin roots.
AB  - An abundant 17 kDa protein which was isolated and characterized from 10-day old
      healthy root tissue of white lupin (Lupinus albus) proved to have a high sequence
      similarity to pathogenesis-related proteins found in other species. Subsequently,
      a corresponding clone (LaPR-10) was identified in a cDNA library prepared from
      the same tissue that exhibited a high amino acid sequence similarity to a number
      of the PR-10 family proteins. The clone contains an open reading frame encoding a
      polypeptide of 158 amino acids, with a predicted molecular mass of 16,905 Da and
      an isoelectric point of 4.66. Southern blot analysis indicates that LaPR-10 is
      likely a single-copy gene, or a member of a small gene family. The clone was
      expressed in Escherichia coli, and its protein product was purified to near
      homogeneity. Both the native and the recombinant proteins were immunorecognized
      by antibodies raised against pea PR-10 proteins, and exhibited a ribonucleolytic
      activity against several RNA preparations, including lupin root total RNA.
      Characterization of its enzymatic properties indicates that the LaPR-10 protein
      belongs to the class II ribonucleases. We present evidence that the white lupin
      17 kDa protein is constitutively expressed during all stages of root development
      and, to a lesser extent, in other plant parts. In addition, we demonstrate the
      presence, in the LaPR-10 amino acid sequence, of a number of motifs that are
      common to most PR-10 proteins, as well as a RGD motif that is shared only with
      the alfalfa SRG1 sequence.

PMID- 10890536
TI  - Cloning, mapping and expression analysis of barley MADS-box genes.
AB  - Six MADS-box cDNA clones were isolated by heterologous screening from a barley
      inflorescence cDNA library. Based on sequence comparison to known MADS-box genes,
      the barley MADS-box (BM) genes were grouped into three distinct phylogenetic
      subclasses of the MADS-box gene family. The three MADS-box genes BM3, BM5 and BM8
      share similarities with genes of the SQUAMOSA (SQUA) subgroup, while BM7 and BM9
      belong to the AGAMOUS-LIKE 2 (AGL2) subgroup. BM1 resembles MADS-box genes
      described as solitary sequences or orphan genes. Expression analysis of the
      barley MADS-box genes revealed expression patterns that are not characteristic of
      the barley MADS-box genes of the SQUA subgroup. while expression of BM7 and BM9
      was largely as expected for the AGL2 subgroup. BM1 is mainly expressed in
      vegetative tissues and its primary transcript undergoes alternative splicing such
      that the corresponding mRNAs differ by two codons. The genes BM1, BM3 and BM8
      were mapped by analysis of single-nucleotide polymorphisms onto barley
      chromosomes 4, 2 and 7, respectively.

PMID- 10890537
TI  - Heterotrimeric G-protein beta-subunit is localized in the plasma membrane and
      nuclei of tobacco leaves.
AB  - Heterotrimeric G-proteins are involved in a variety of cellular responses, but
      relatively little is known about their function and biochemistry in plants.
      Antibodies raised against the tobacco heterotrimeric G-protein beta-subunit
      (Gbeta) were used to analyse its distribution in tobacco leaves. In young tissue
      the protein level was relatively high, while it declined substantially during
      later stages of leaf development. Cell fractionation revealed that Gbeta is
      tightly associated with plasma membrane, but can also be detected in purified
      nuclei.

PMID- 10890538
TI  - Characterization of a small GTP-binding protein of the rab 5 family in
      Mesembryanthemum crystallinum with increased level of expression during early
      salt stress.
AB  - A cDNA encoding a member of the Ypt/Rab family of small GTP-binding proteins was
      cloned from the facultative CAM plant Mesembryanthemum crystallinum. Mcrab5b
      includes an open reading frame of 201 amino acids. The deduced amino acid
      sequence shows 91% similarity to LjRAB5b isolated from Lotus japonicus. The amino
      acid sequence of McRAB5b provides interesting features suggesting that McRAB5b
      and its homologue from Lotus japonicus represent a new subclass of Ypt/Rab
      proteins. The fact that proteins like McRAB5b and LjRAB5b were only found in
      plants and not in yeast or vertebrates suggests that they have plant-specific
      functions. The expression of Mcrab5b as investigated by northern blot
      hybridization and RT-PCR was stimulated under salt stress. After heterologous
      expression in Escherichia coli an antibody was raised against recombinant McRABSb
      protein. Western blot analysis revealed that McRAB5b was bound to membranes. It
      is present in a monomeric and a dimeric form in vitro and in vivo. In vitro only
      the monomeric protein exhibits a binding capacity for radiolabelled GTP, while
      the dimer is unable to do so, indicating that the activity may be regulated by
      monomer/dimer transition.

PMID- 10890539
TI  - Angiogenesis and surgery: from mice to man.

PMID- 10890540
TI  - Long term response to gallstone treatment--problems and surprises.
AB  - OBJECTIVE: To re-evaluate after 5 years the results of a randomised trial of
      cholecystectomy and lithotripsy for the treatment of symptomatic gallstones.
      DESIGN: Late follow-up of a randomised controlled trial. SETTING: Teaching
      hospital, UK. SUBJECTS: 144 of the 179 patients originally randomised.
      INTERVENTIONS: Either elective open cholecystectomy under general anaesthesia or
      a maximum of 4 sessions of lithotripsy (up to 3000 shocks/session) on consecutive
      days with no anaesthesia or analgesia. RESULTS: Of the original 87 patients
      randomised to be treated by lithotripsy, 39 (45%) subsequently underwent
      cholecystectomy, most of them within 32 months of treatment ("crossover" group).
      Patients in both main groups had a pronounced reduction in the number of episodes
      of pain at 5 years and significant reductions in the mean severity scores both on
      VAS and the McGill rating. Those in the crossover group had the worst scores.
      Gastrointestinal symptoms improved in the two main groups, but again the
      crossover group did least well. Quality of life improved significantly over
      baseline in the two main groups, but was much poorer in the crossover group.
      CONCLUSIONS: Patients who had primary cholecystectomy were more likely to be free
      of pain than those treated by lithotripsy. Lithotripsy gave good symptomatic
      results in 55% of patients, and this was not dependent on clearance of stones.
      Patients who had a cholecystectomy after lithotripsy had the worst symptomatic
      results. It is difficult to identify patients who will not benefit from
      lithotripsy, but the presence of many coexisting symptoms may be an important
      predictor.

PMID- 10890541
TI  - Painless lithotripsy by flashlamp-excited dye laser for impacted biliary stones:
      an experimental and clinical study.
AB  - OBJECTIVE: To find out the appropriate dye laser output and frequency for each
      kind of stone experimentally, and to use flashlamp-excited dye laser for impacted
      biliary stones. DESIGN: Prospective study. SETTING: University hospital, Japan.
      SUBJECTS: 12 patients undergoing lithotripsy for both intrahepatic and
      extrahepatic impacted biliary stones. MAIN OUTCOME MEASURES: Appropriate dye
      laser output and frequency, histological changes in the bile duct wall, and
      outcome. RESULTS: Stones were pulverised, and required a median 155 pulses (range
      80-205) at 40 mJ for bilirubin stones and 355 pulses (range 205-405) at 50 mJ for
      cholesterol stones. At the standard energies used, the laser caused only
      superficial damage to the serosa of the common bile duct. It was successful in
      fragmenting 133/135 stones (99%), and in addition pulverised 125/135 stones
      (93%). No patients complained of pain during laser lithotripsy even under local
      anaesthesia. All patients were discharged from the hospital after an uneventful
      recovery, and no recurrent stones have been found at outpatient follow-up ranging
      between 2 and 85 months. CONCLUSION: Flashlamp-excited dye laser with a small
      choledochoscope seems to be safe and painless way of treating biliary stones,
      even if they are impacted in the peripheral biliary tree and patients are at high
      risk.

PMID- 10890542
TI  - Endotoxin and antiendotoxin antibodies in patients with acute pancreatitis.
AB  - OBJECTIVE: To elucidate the time course of endotoxaemia and antiendotoxin
      antibodies in patients with acute pancreatitis. DESIGN: Prospective clinical
      study. SETTING: University hospital, Germany. SUBJECTS: 25 patients with
      oedematous (n = 9) or necrotising (n = 16) pancreatitis, and 20 healthy controls.
      MAIN OUTCOME MEASURES: Concentrations of endotoxin and immunoglobulins (classes
      G, M, and A) directed at two lipid A molecules, four lipopolysaccharides, and
      alpha-haemolysin of Staphylococcus aureus measurements in plasma during a 12 day
      period. RESULTS: There were no differences in the degree of endotoxaemia between
      patients with oedematous and necrotising pancreatitis on admission. However, from
      the day after admission and throughout the observation period patients with
      necrotising pancreatitis had significantly higher concentrations of endotoxin
      than those with oedematous pancreatitis. Concentrations of IgM specific for
      endotoxin peaked at day 4, and then decreased in patients with oedematous
      pancreatitis while remaining high for those with necrotising pancreatitis. There
      was only a slight increase in IgA specific for endotoxin, and IgG and
      immunoglobulins to gamma-haemolysin remained steady throughout the observation
      period. There was strong cross-reactivity (r > 0.7) between IgM specific for
      endotoxin (70%), but this was less with IgA (52%), and IgG (20%). CONCLUSIONS:
      Necrotising pancreatitis is accompanied by persistent endotoxaemia with an
      extended rise in antiendotoxin antibodies. Patients with oedematous pancreatitis
      have a transient endotoxaemia with a temporary increase of Ig specific for
      endotoxin. Endotoxin stimulates the synthesis of specific antibodies (IgM)
      despite general immunosuppression.

PMID- 10890543
TI  - Systemic stress responses after laparoscopic or open hernia repair.
AB  - OBJECTIVE: To compare systemic stress responses after laparoscopic and open
      hernia repair to find out if the laparoscopic approach caused less stress than an
      open operation. DESIGN: Prospective randomised trial. SETTING: Teaching hospital,
      Sanliurfa, Turkey. SUBJECTS: 50 patients who required preperitoneal hernia repair
      were randomised to be treated by either the open or laparoscopic approach (n = 25
      in each). INTERVENTIONS: Samples of venous blood were taken before operation and
      at 2, 24, and 48 hours afterwards for measurement of the concentrations of:
      glucose, cortisol, malonyldialdehyde (MDA), C-reactive protein (CRP), creatine
      phosphokinase (CPK), caeruloplasmin, transferrin, fibrinogen, and albumin, and
      counts of leucocytes, neutrophils, and lymphocytes. MAIN OUTCOME MEASURES:
      Changes in these indicators of a stress response. RESULTS: Concentrations of
      glucose, cortisol, CRP, MDA, and CPK, and counts of leucocytes and neutrophils
      increased significantly, and the concentration of albumin decreased
      significantly, in both groups postoperatively. Lymphocyte counts were lower
      postoperatively but not significantly so. Concentrations of CRP, MDA, and CPK,
      and leucocyte counts were significantly lower in the laparoscopic group.
      CONCLUSION: These findings suggest that there is less systemic stress response
      after laparoscopic than after open hernia repair.

PMID- 10890544
TI  - Survival after operations for colorectal cancer in patients aged 75 years or
      over.
AB  - OBJECTIVE: To define factors that predict mortality and survival in patients with
      colorectal cancer who are aged 75 or over. DESIGN: Retrospective study. SETTING:
      University hospital, Finland. SUBJECTS: 231 patients aged 75 or over who were
      admitted to hospital with colorectal cancer during the 14-year period 1980-93.
      MAIN OUTCOME MEASURES: Morbidity, mortality, recurrence, and survival. RESULTS:
      In-hospital mortality after any kind of operation was 8/211 (4%), and 8/175 (5%)
      of those who had their tumours resected. Morbidity was 35/175 (20%). Factors
      associated with mortality were weight loss, Dukes'stage, extent of resection, and
      type of operation. Overall 5-year survival was 28%, overall 10-year survival was
      4%, and median survival was 33 months (range 0-150). Survival was most closely
      related to Duke's stage, extent of resection, and recurrent disease on univariate
      analysis, but multivariate analysis identified only mode of recurrence (p <
      0.0001), recurrent disease (p < 0.004), and extent of resection (p < 0.009) as
      independent predictors of survival. The recurrence rate after radical resection
      was 49/141 (35%) and the median disease-free interval was 10 months (range 4-64).
      Mortality after resection for recurrent cancer was 3/17 (18%) and morbidity 5/17
      (29%). CONCLUSION: Age alone is not a risk factor for postoperative mortality or
      a predictor of long-term survival. Low mortality and acceptable long-term
      survival can be achieved in patients aged 75 or over if those with extensive
      distant metastases, and those whose general condition is too poor to stand a
      major operation, are treated conservatively.

PMID- 10890545
TI  - Functional results after treatment of hip fracture: a multicentre, prospective
      study in 215 patients.
AB  - OBJECTIVE: To find out which factors influence outcome after a fractured hip, so
      that the optimum treatment may be chosen for each patient. DESIGN: Prospective
      cohort study. SETTING: 3 teaching and 2 rural hospitals, The Netherlands.
      SUBJECTS: 215 patients aged 55-102 years (median 82) who presented with a
      fractured hip during 1994. INTERVENTIONS: Interviews shortly after the injury and
      4 and 12 months later, study of radiographs, and evaluation of casenotes. MAIN
      OUTCOME MEASURES: Mobility and functional recovery. RESULTS: 38 patients had died
      by the 4-month follow up, at which time 64/177 (36%) had regained the level of
      mobility that they had before the injury. At 12 months the figure was 58/148
      (39%). The corresponding figures for functional recovery were 52/177 (29%) and
      36/148 (24%). Factors that militated against recovery were increasing age,
      coexisting diseases, general complications and local complications. CONCLUSIONS:
      The chance of a patient with a hip fracture making any further recovery after 4
      months is minimal. Local complications are the most important risk factor.

PMID- 10890546
TI  - Healing of porcine donor sites covered with silver-coated dressings.
AB  - OBJECTIVE: To compare rates of healing of donor sites in pigs between those
      dressed with silver-coated dressings and those dressed with petrolatum
      impregnated absorbent gauze. DESIGN: Open study with each animal acting as its
      own control. SETTING: University research facility, Canada. ANIMALS: 6 young
      specific-pathogen-free domestic pigs. INTERVENTIONS: A total of 72 wounds about 1
      cm x 2 cm x 0.4 mm were made in rows of eight on each pig with a dermatome. They
      were divided into three groups of 24, and dressed with petrolatum gauze, or
      silver-coated dressings moistened with sterile water either once only or daily
      for 10 days. All dressings were secured in place with an elastic bandage. MAIN
      OUTCOME MEASURES: Erythema, infection, epidermal migration, and healing. RESULTS:
      Wounds dressed with moistened silver-coated dressings re-epithelialised
      significantly more quickly. This resulted in complete re-epithelialisation within
      70% of the time taken by those wounds dressed with petrolatum gauze. CONCLUSION:
      Silver-coated dressings provide a moist environment for the healing wound
      combined with an effective antimicrobial agent, and this significantly
      accelerates healing compared with wounds dressed with traditional petrolatum
      gauze dressings.

PMID- 10890547
TI  - An experimental study of the adhesive potential of different meshes.
AB  - OBJECTIVE: To assess the adhesive potential and incidence of incisional hernia
      with three meshes. DESIGN: Open experimental study. SETTING: Surgical Research
      Laboratory, Turkey. ANIMALS: 75 Wistar albino rats INTERVENTIONS: Abdominal walls
      were excised, and defects closed primarily or with polyglactin 910,
      polypropylene, or dura mater. Adhesions were graded and hydroxyproline
      concentrations measured on days 14 and 180. On day 180, the incidence of
      incisional hernia, and the grades of inflammation and fibrosis were also
      recorded. RESULTS: The polyglactin 910 group had a higher adhesion grading than
      the control and dura mater groups on day 14, whereas the polypropylene group had
      higher adhesion grading than controls. Both polypropylene and polyglactin 910
      groups had significantly higher concentration of hydroxyproline than the control
      and dura mater groups. On day 180, the polypropylene group had a higher adhesion
      grading than the controls. There were no differences in hydroxyproline
      concentrations, incidence of hernias, or grading of fibrosis levels among the
      groups. CONCLUSION: Polyglactin 910 induced more fibrotic adhesions in the early
      postoperative period whereas polypropylene did in both the early and late
      postoperative periods.

PMID- 10890548
TI  - Hepatic vascular exclusion without cross-clamping the inferior vena cava for
      liver resections.

PMID- 10890549
TI  - Tricks in the technique of lateral pancreaticojejunostomy.

PMID- 10890550
TI  - Full thickness chest wall resection for solitary sternal metastasis in breast
      carcinoma.

PMID- 10890551
TI  - Duodenal duplication cyst communicating with the bile duct with a long common
      biliary-pancreatic channel.

PMID- 10890552
TI  - Horseshoe shaped ectopic cervical thymus extending into the anterior mediastinum.

PMID- 10890553
TI  - Raised tissue copper levels in oral submucous fibrosis.
AB  - Oral submucous fibrosis (OSF) is a well-recognised-potentially malignant
      condition of the oral cavity associated with areca nut chewing. Areca nut has
      been shown to have a high copper content compared to other commonly eaten nuts,
      and chewing areca nut for 5-30 min significantly increases soluble copper in
      whole mouth fluids. Our aims were to determine if tissue and serum concentrations
      of copper were raised in patients with OSF as a result of chewing areca nut. A
      panel of buccal mucosal biopsies from patients with OSF from Nagpur, India, was
      used to measure the tissue concentrations of copper by mass absorption
      spectrometry (MAS). By MAS, the mean tissue copper level was 5.5+/-2.9 microg/g
      in the OSF specimens (n=11) compared with 4+/-1.9 microg/g in the non-areca
      chewing controls (n=7) (P=0.2). Energy dispersive x-ray microanalysis (EDX) was
      used to identify the presence and distribution of the metal element. EDX showed
      distinct peaks corresponding to copper (Kalpha 8.04 keV; Kbeta, 8.91 keV) in the
      epithelium (21/23) and in the connective tissue (17/23) of the OSF specimens
      compared to spectra obtained from control oral biopsies from non-areca chewing
      subjects (n=7). These findings were confirmed by secondary ion mass spectrometry
      (SIMS) analysis in a small number of samples. Serum copper (17.23+/-1.80 pmol/l),
      caeruloplasmin (0.32+/-0.04 g/l) levels and urinary copper (0.52+/-0.26
      micromol/l) in OSF patients (n=14) were within the laboratory reference ranges.
      The finding of copper in OSF tissue supports the hypothesis of copper as an
      initiating factor in OSF, playing a role in stimulating fibrogenesis by the
      upregulation of lysyl oxidase activity.

PMID- 10890555
TI  - Hepatitis C virus infection and oral lichen planus: a report from The
      Netherlands.
AB  - The reported frequency of anti-hepatitis C virus (HCV) antibodies in groups of
      cutaneous lichen planus (CLP) and/or oral lichen planus (OLP) patients varies
      from about 4% to 65%. Most of these studies have been performed in countries with
      a high overall prevalence of HCV infection in the general population, such as the
      southern European countries and Japan. Limited data are available from areas with
      a low prevalence of HCV infection. Therefore, we investigated the prevalence of
      HCV infection in a series of 55 patients with OLP in the Netherlands, which
      apparently has a low prevalence of HCV infection. None of the 55 patients
      revealed serological evidence of antibodies to HCV. The present data suggest that
      HCV infection in OLP patients in the Netherlands is probably not very common. A
      larger study group with a sex- and age-matched control group is required to
      advise against routine serological examination for HCV infection in Dutch OLP
      patients.

PMID- 10890554
TI  - A study to assess inducible nitric oxide synthase expression in oral lichen
      planus.
AB  - Nitric oxide (NO) has been implicated in a variety of diseases but has not been
      previously studied in oral lichen planus (OLP). Since OLP has a complex
      immunogenesis with abundant macrophage infiltration, this study determined by
      immunohistochemistry whether or not the expression of the inducible form of
      nitric oxide synthase (iNOS) was increased in this condition relative to normal
      mucosa. Thirty cases of OLP and 10 normal buccal mucosa biopsies were studied
      utilising primary antibodies to iNOS and CD68, a myelomonocytic marker. iNOS
      activity was additionally assessed using a [(14-)C]-labelled arginine to
      citrulline assay. CD68 expression was significantly increased in the cellular
      infiltrate of all 30 cases of OLP compared with normal mucosa (P<0.009). Although
      iNOS staining was seen in a minority of cells in nine cases, this was not
      statistically significant when compared with the absent staining in normal oral
      mucosa (P=0.26). Furthermore, the minimal iNOS activity found in OLP was similar
      to that in normal mucosa. We conclude that expression of iNOS by macrophages is
      downregulated in OLP and discuss the possible reasons for this finding.

PMID- 10890556
TI  - Detection of hepatitis C virus RNA in oral lichen planus and oral cancer tissues.
AB  - Hepatitis C virus (HCV) infection not only causes chronic liver diseases but
      shows extrahepatic manifestations as oral lichen planus (OLP) and oral cancer. To
      elucidate the direct relationships among these diseases and HCV infection, we
      investigated the detection of positive- and negative-strand HCV-RNA from serum,
      OLP (n=19), and oral cancer (n=17) tissues. We used a sensitive reverse
      transcription to polymerase chain reaction (RT-PCR) method, and analyzed
      sequences from the HCV El/E2 region of the genome from serum and tissue. Positive
      and negative HCV-RNA strands were observed in 13 (92.9%) and 3 (21.4%) OLP
      tissues, respectively. In oral cancer tissues, positive HCV-RNA strands were
      detected in all tissues from anti-HCV positive patients. Negative HCV-RNA strands
      were observed in 5 of 7 (71.4%) patient's tissues. Furthermore, it was confirmed
      that the sequence from one of each OLP and oral cancer patient differed between
      serum and tissue HCV-RNA. These results may indicate that HCV persists and
      replicates in these lesions, suggesting a pathological role for HCV, although the
      mechanisms are unclear.

PMID- 10890557
TI  - Salivary oncofoetal fibronectin and oral squamous cell carcinoma.
AB  - Fibronectin (FN) is a multifunctional adhesive glycoprotein that exists in the
      extracellular matrix and body fluids. As a result of alternative splicing, extra
      segments (ED-A and ED-B) may be included in the fibronectin molecule. These
      isoforms of FN, together with FN that has an extra glycosylation (OFFN), are
      strongly associated with a number of tumours, including oral squamous cell
      carcinoma (SCC). In view of the likely exfoliation of these cells into the oral
      cavity from tumours, OFFN might be present in saliva. As such, the presence of
      OFFN in saliva may be an indicator of oral SCC. The saliva of 12 patients with
      oral squamous carcinoma and 8 disease-free individuals was measured for OFFN
      using an enzyme-linked immunoassay. Salivary OFFN levels were similar for
      patients both with oral SCC and those without, suggesting that this would not be
      a useful test for the detection of oral SCC.

PMID- 10890558
TI  - Fas expression and Fas monoclonal antibody-induced apoptosis in a human squamous
      cell carcinoma cell line, SCC-25.
AB  - Fas antigen is a cell surface protein that mediates apoptosis via signal
      transduction from the plasma membrane. Using reverse transcriptase-polymerase
      chain reaction (RT-PCR), messenger RNA for Fas antigen was detected in the human
      oral squamous cell carcinoma cell line, SCC-25. In serum-free medium, a
      monoclonal anti-Fas antibody (CH-11) induced Fas antigen expression in SCC-25
      cells, as determined by immunocytochemistry and Western blotting, using an anti
      Fas polyclonal antibody (Fas D) as primary antibody. Fas antigen was localized to
      the cytoplasm and the cell membrane. The molecular weight of the protein
      recognized by Western blot analysis was 35,000, consistent with the value
      reported for the Fas antigen. The CH-11 antibody did not induce Fas antigen
      expression in serum-containing medium. To determine whether CH-11 could induce
      apoptosis in oral squamous cell carcinoma, we examined its effects on the
      survival of cultured SCC-25 cells. Anti-Fas monoclonal antibody in serum-free
      medium induced cytotoxicity in SCC-25 cells in a time-dependent manner up to 8 h,
      as determined by phase-contrast microscopy and WST-1 assay. Marked nuclear
      condensation and fragmentation of chromatin were observed in the CH-11-treated
      cells using Hoechst 33342 staining. This anti-Fas monoclonal antibody also
      induced DNA ladder formation in SCC-25 cells in a time-dependent manner. The
      present results indicate that the anti-Fas monoclonal antibody (CH-11) may
      mediate apoptosis by binding to the Fas antigen expressed in SCC-25 cells.

PMID- 10890559
TI  - Are myoepithelial cells responsible for the widespread expression of inducible
      nitric oxide synthase in pleomorphic adenoma? An immunohistochemical study.
AB  - Many of the actions of nitric oxide (NO) are still poorly understood. Recently,
      it has been shown that the inducible isoform of the enzyme nitric oxide synthase,
      iNOS, is expressed in both salivary ducts and pleomorphic adenoma. The current
      immunohistochemistry study determined whether or not this distribution correlated
      with smooth muscle actin (SMA) expression, thereby suggesting the expression by
      myoepithelial cells in both sites. Twenty cases of histologically confirmed
      pleomorphic adenoma, the sections of which contained adjacent normal salivary
      gland tissue, were stained for iNOS and smooth muscle actin (clone 1A4). The
      salivary ducts of all cases were stained intensely by both antibodies, with
      smooth muscle actin staining also being noted around acini in the normal gland
      parenchyma. Moderate or heavy staining for iNOS was found in all specimens of
      pleomorphic adenoma, with smooth muscle actin being distributed in a similar
      manner in 19 cases. Smooth muscle actin, but not iNOS, was also noted in blood
      vessels of both normal glands and tumours. The correlation between iNOS and SMA
      in pleomorphic adenoma was significant (P<0.001). The presence of iNOS in normal
      salivary ducts and pleomorphic adenoma is most likely due to expression by
      myoepithelial cells.

PMID- 10890560
TI  - Cellular heterogeneity of granular cell tumours: a clue to their nature?
AB  - Most granular cell tumours (GCTs) are benign proliferations of purported
      Schwannian derivation, showing immunoreactivity for Schwann cell-related
      antigens. Due to incomplete agreement on the precise nature of GCTs (reactive vs
      neoplastic), we performed an immunohistochemical study with the alkaline
      phosphatase/anti-alkaline phosphatase (APAAP) technique on 30 GCTs. The aim was
      to evaluate their growth patterns and the possible relationships of granular
      cells with other nerve sheath-related cell types (i.e., Schwann and perineurial
      cells, and dendritic cells displaying CD34/vimentin immunoreactivity). An
      expansive growth pattern was detected in five cases, a pseudoinfiltrative growth
      pattern in nine cases and a mixture of the above in the remaining 16 cases.
      Besides immunoreactivity for S-100 protein, neuron-specific enolase, vimentin,
      CD57, CD68, MAC 387, alpha-1-antitrypsin and alpha-1-antichymotrypsin in granular
      cells, we documented intimate architectural relationships between granular cells,
      Schwann and perineurial cells, and a third type of CD34/vimentin-positive nerve
      sheath-related cell in most GCTs. These results suggest that GCTs are
      heterogeneous lesions. Some of them show a pseudoinfiltrative growth pattern and
      retain close relationships with the normal components of the nerve sheath. In
      other lesions, granular cells grow in an expansive fashion and constitute the
      predominant cell component of the tumour. These architectural and
      immunophenotypic differences may reflect a different nature of GCTs: they may
      initially represent reactive or hamartomatous lesions that subsequently acquire
      truly neoplastic potential.

PMID- 10890561
TI  - Mammalian mesotocin: cDNA sequence and expression of an oxytocin-like gene in a
      macropodid marsupial, the tammar wallaby.
AB  - The oxytocin (OT)-like peptide of most Australian marsupials is mesotocin (MT),
      which differs from OT by substitution of isoleucine for leucine at position 8. To
      date, the only information on the evolution of the OT peptide in marsupials is
      based on the sequence of the 9-amino acid peptide itself. The main objective of
      this study was to obtain the nucleotide and derived amino acid sequences of a
      marsupial MT precursor for comparison with known OT and MT precursors of
      eutherians and nonmammalian vertebrates. The structural organization and sequence
      of the MT gene and its specific transcript were established in a macropodid
      marsupial, the tammar wallaby, using PCR strategies with a combination of genomic
      DNA and reverse-transcribed hypothalamic RNA. A consensus genomic sequence of
      1221 bp was produced which, by comparison with the expressed cDNA sequence,
      included two intron sequences of 480 and 188 bp. The tammar MT precursor molecule
      consists of a 32-amino acid signal peptide, followed by the MT-encoding region
      and the Gly-Lys-Arg carboxy-terminal cleavage and amidation signal which
      separates the nonapeptide from the 92-amino acid neurophysin. At the amino acid
      level, the MT precursor is more similar to eutherian OT precursors than to
      nonmammalian MT, isotocin, or vasotocin precursors. Northern analysis
      demonstrated a single transcript of approximately 0.6 kB in the hypothalamus.
      Mesotocin mRNA is also present in several tissues of the reproductive tract,
      including the corpus luteum, follicle, uterus, and placenta. Within the ovary, MT
      transcripts are localized predominantly in the granulosa cells of antral
      follicles with some positive hybridization signals in cells of the theca interna.
      This pattern of MT gene expression in marsupials is very similar to that of OT in
      eutherians and suggests a conserved physiology in the mammalian ovary.

PMID- 10890562
TI  - Changes in protein kinase C during vitellogenesis in the crayfish Cherax
      quadricarinatus--possible activation by methyl farnesoate.
AB  - During ovarian maturation in the crayfish Cherax quadricarinatus, changes in
      ovarian protein kinase C (PKC) isoenzymes take place in parallel to yolk
      accumulation (as shown by immunoblot analysis). Significant changes were recorded
      in the amounts of specific isoenzymes and in their distribution between the
      cytosol and the membranes. Ovarian maturation was accompanied by the appearance
      of high- and low-molecular-weight immunoreactive PKC isoenzyme species. Among the
      isoenzymes tested, PKC alpha was the most clearly activated during ovarian
      maturation, as shown by significant translocation from the cytosol to the
      particulate fraction and the appearance of high-molecular-weight species.
      Moreover, a similar picture was obtained in the ovaries of intersex individuals
      upon induction of secondary vitellogenesis by androgenic gland ablation.
      Immunohistological staining showed PKC alpha to be localized mainly in the
      cytosol of premature oocytes, whereas in later maturation stages, it was
      concentrated around the nucleus in a vesicular structure and in the oocyte
      membrane. In secondary vitellogenic stages, PKC was localized in the plasma
      membrane and apparently in follicular cells. In addition, its activity was
      demonstrated by in vitro phosphorylation assays of a crayfish ovarian homogenate.
      Activation of total PKC phosphorylation of histone, an external substrate, was
      induced by phosphatidylserine plus 12-O-tetradecanoylphorbol-13-acetate (TPA) or
      methyl farnesoate. Both TPA and methyl farnesoate stimulated activation of PKC
      alpha in organ culture, causing its translocation from the cytosol to the
      membranes and inducing autophosphorylation of threonine residues. The changes in
      PKC isoenzymes during ovarian maturation in the crayfish suggest their
      involvement in this process as well as a possible regulatory role for methyl
      farnesoate through a direct effect on some PKC isoenzymes.

PMID- 10890563
TI  - Annual cycles of steroid hormone production, gonad development, and reproductive
      behavior in the Atlantic stingray.
AB  - The mating season of the Atlantic stingray (Dasyatis sabina), which begins in
      August and continues through April, is the longest documented for any
      elasmobranch fish. Despite this protracted mating period, female stingrays
      ovulate synchronously at the end of the mating season and there is no evidence
      for sperm storage by females. Thus, the proximate causal factors and ultimate
      function of this extended preovulatory mating are unknown. Annual cycles of the
      gonadal steroids testosterone (T), dihydrotestosterone (DHT), 17beta-estradiol
      (E2), and progesterone (P4) were measured for 26 months in a wild estuarine
      population of Atlantic stingrays to test for associations with their reproductive
      biology, gametogenesis, and sexual behavior. Serum androgen levels in males
      showed four phases within an annual cycle: (1) androgen suppression between
      reproductive seasons (April-July), (2) primary androgen increase during the onset
      of spermatocyte development (August-October), (3) androgen decrease following
      maximum testis growth and spermatocyte development (November-December), and (4)
      secondary androgen increase during the peak of sperm maturation (January-March).
      Increases in male E2 and P4 were correlated with spermatocyte/spermatocyst
      formation, maximum testis weight, and the primary (but not secondary) androgen
      surge. We propose that the production of male androgens across the full seven
      month preovulatory mating period promotes their aggressive reproductive behavior
      and drives the protracted mating season of this species. In females, serum T and
      DHT showed relatively brief increases near ovulation, whereas E2 and P4 showed
      brief increases near both ovulation and parturition. The increase in female
      androgens near ovulation may increase female aggression when they are impregnable
      by courting males and enhance their choice of mates. This estuary sample
      population shows higher absolute steroid levels and distinct differences in
      temporal cycles compared to another Florida fresh water lake population, but the
      cause and significance of these differences are unknown. Experiments are needed
      to confirm that the aggressive and protracted mating behavior is the result of
      prolonged male androgen production and to determine whether the sustained
      preovulatory mating serves some function related to female reproduction.

PMID- 10890564
TI  - Differential distribution of gonadotropin-releasing hormone-immunoreactive
      neurons in the stingray brain: functional and evolutionary considerations.
AB  - Gonadotropin-releasing hormone (GnRH) is a neuropeptide that occurs in multiple
      structural forms among vertebrate species. Bony fishes, amphibians, reptiles,
      birds, and mammals express different forms of GnRH in the forebrain and endocrine
      regions of the hypothalamus which regulate the release of reproductive
      gonadotropins from the pituitary. In contrast, previous studies on bony fishes
      and tetrapods have localized the chicken GnRH-II (cGnRH-II) nucleus in the
      midbrain tegmentum and, combined with cladistic analyses, indicate that cGnRH-II
      is the most conserved form throughout vertebrate evolution. However, in
      elasmobranch fishes, the neuroanatomical distribution of cGnRH-II and dogfish
      GnRH (dfGnRH) cells and their relative projections in the brain are unknown. We
      used high-performance liquid chromatography and radioimmunoassay to test for
      differential distributions of various GnRH forms in tissues from the terminal
      nerve (TN) ganglia, preoptic area, and midbrain of the Atlantic stingray,
      Dasyatis sabina. These experiments identified major peaks that coelute with cGnRH
      II and dfGnRH, minor peaks that coelute with lamprey GnRH-III (lGnRH-III), and
      unknown forms. Immunocytochemistry experiments on brain sections show that dfGnRH
      immunoreactive (-ir) cell bodies are localized in the TN ganglia, the caudal
      ventral telencephalon, and the preoptic area. Axons of these cells project to
      regions of the hypothalamus and pituitary, diencephalic centers of sensory and
      behavioral integration, and the midbrain. A large, discrete, bilateral column of
      cGnRH-II-ir neurons in the midbrain tegmentum has sparse axonal projections to
      the hypothalamus and regions of the pituitary but numerous projections to sensory
      processing centers in the, midbrain and hindbrain. Immunocytochemical and
      chromatographic data are consistent with the presence of lGnRH-III and other GnRH
      forms in the TN that differ from dfGnRH and cGnRH-II. This is the first study
      that shows differential distribution of cGnRH-II and dfGnRH in the elasmobranch
      brain and supports the hypothesis of divergent function of GnRH variants related
      to gonadotropin control and neuromodulation of sensory function.

PMID- 10890565
TI  - Bovine adrenal cells secrete interleukin-6 and tumor necrosis factor in vitro.
AB  - Interleukin-6 (IL-6) and tumor necrosis factor (TNF) are secreted and/or
      synthesized by the rat and human adrenal cortex. In this study, the release of IL
      6 and TNF from bovine adrenal cells was determined. Bovine adrenal glands were
      collected from an abattoir and dissected into the zona glomerulosa (ZG), zona
      fasciculata (ZF), zona reticularis (ZR), and medulla. The tissues were
      enzymatically dispersed to single cells and cultured for 4-6 days. The cells were
      then exposed (4 h) to angiotensin II (AII), adrenocorticotrophic hormone (ACTH),
      phorbol dibutyrate (PDB), interleukin-1beta (IL-1beta), interleukin-1alpha (IL
      1alpha), and endotoxin (LPS). The IL-6 and TNF content of the incubation medium
      was determined by bioassays. The release of IL-6 and TNF from the ZG, ZF, ZR, and
      medulla was increased by PDB, IL-1alpha, IL-1beta, and LPS. In contrast, ACTH and
      AII increased IL-6 release from the ZG, ZF, and ZR but had no effect on IL-6
      release from the medulla. ACTH decreased TNF release from all adrenal cortical
      zones but had no effect on TNF release from the medulla. Immunohistochemistry
      utilizing antibodies against TNFalpha demonstrated TNFalpha-containing cells
      throughout the adrenal gland. The majority of the cells of the ZG, ZF, and ZR
      contained TNFalpha. However, the cells of the ZG contained more TNFalpha than the
      cells of the ZR or ZF. Small patches of TNFalpha-containing cells were also found
      in the adrenal medulla and capsule. These findings support the hypothesis that IL
      6 and TNF may have autocrine/paracrine effects on the adrenal gland.

PMID- 10890566
TI  - Seasonal relationships between plasma and fecal testosterone in response to GnRH
      in domestic ganders.
AB  - In two groups (eight individuals each) of socially acquainted, outdoor-kept,
      domestic ganders (male Hungarian white: Anser domesticus), basal and GnRH
      stimulated plasma testosterone (T) concentrations were compared with fecal
      testosterone metabolites (TM) in and between three seasons, spring peak of
      reproductive activity, summer photorefractoriness, and fall sexual reactivation.
      Plasma was sampled 90 min following the challenge and T was analyzed by
      radioimmunoassay following the GnRH challenge. Fecal TM were measured by enzyme
      immunoassay using two group-specific antibodies against 17beta-OH-androgens or a
      novel antibody against 17-oxo groups, which was found to react with major
      testosterone metabolites without prior hydrolytic deconjugation. Baseline plasma
      T and systemic levels were high in spring and fall but low in summer. Plasma T
      increases in response to GnRH were followed by significantly elevated fecal TM
      levels 2 to 6 h following the challenge in spring and fall. In fall, at high
      plasma T levels, fecal TM levels were disproportionally lower than in spring.
      Variability of TM levels was two to five times higher in feces than in plasma,
      which explains why correlations between individual plasma T and fecal TM levels
      generally remained nonsignificant. This points to a low-level short-term
      relationship between the excreted TM and the plasma T levels. However, the
      reliability of the method was demonstrated by standard inter- and intraassay
      variabilities and by a high correspondence between results obtained by the two
      assays. It is suggested that, with appropriate sample size, fecal TM reflects
      plasma T increase. However, fecal TM was more variable than the plasma T, and
      fecal TM responses to GnRH did not always parallel the plasma T response. In
      addition, seasonal changes in androgen excretion regimes must be taken into
      account.

PMID- 10890567
TI  - The role of steroid hormones in protogynous sex change in the Blackeye goby,
      Coryphopterus nicholsii (Teleostei: Gobiidae).
AB  - To detect and describe correlations between steroid concentrations and sexual
      function in the protogynous Coryphopterus nicholsii, we examined whole-body
      concentrations of the gonadal steroids testosterone (T), 11-ketotestosterone (11
      KT), and 17beta-estradiol (17beta-E2). Our results show that T, 11-KT, and 17beta
      E2 are naturally occurring steroids in both female and male C. nicholsii.
      Further, mean whole-body concentrations of T and 11-KT in males were
      approximately twice those in females, whereas mean whole-body concentration of
      17beta-E2 in females was almost twice that in males. Second, we tested hypotheses
      on the causation of sex change arising from these correlations between steroid
      concentrations and sexual function. We examined the effects of administration of
      11-KT, 11-KA, 17alpha-methyltestosterone, and an aromatase inhibitor (Fadrozole)
      on gonadal structures of mature females. Complete sex change was induced by 11
      KT, 11-KA, and Fadrozole. Our results strongly suggest that an increase in 11-KT
      concentration and perhaps also a decrease in 17beta-E2 concentration are involved
      in mediating natural sex change in C. nicholsii.

PMID- 10890568
TI  - Distinct specificity for corticosteroid binding sites in amphibian cytosol,
      neuronal membranes, and plasma.
AB  - To address mechanisms of corticosteroid action, one needs tools for
      distinguishing between the major classes of corticosteroid binding sites:
      neuronal membrane-associated receptors, intracellular ligand-activated
      transcription factors, and corticosteroid binding globulins (CBG) in plasma. We
      characterized the binding parameters for three classes of binding sites in an
      amphibian, Ambystoma tigrinum, and found that each class had a distinct
      pharmacological specificity. Equilibrium saturation and kinetic experiments
      indicated that [3H]corticosterone binds to neuronal membranes with high affinity
      (Kd approximately 0.37 nM). Aldosterone and two synthetic ligands for mammalian
      intracellular receptors, dexamethasone and RU486, displayed low affinity for
      brain membrane sites. In cytosol prepared from brain and liver,
      [3H]corticosterone bound to a single class of receptors with high affinity (Kd
      approximately 0.75 and 4.69 nM, respectively) and the rank order potencies for
      steroid inhibition of [3H]corticosterone binding was RU486 > dexamethasone
      approximately = corticosterone > aldosterone. In kidney and skin cytosol,
      [3H]corticosterone binding was best fit with a model having a high-affinity and a
      lower-affinity site; these sites are not consistent with the pharmacology of
      mammalian Type I (MR) and Type II (GR) receptors. [3H]Corticosterone also bound
      to presumed CBG in plasma with high affinity (Kd approximately 2.7 nM), but
      dexamethasone and androgens bound to plasma CBG with equivalently high affinity.
      These data demonstrate that pharmacological specificity can be a useful tool for
      distinguishing corticosteroid binding to different classes of binding sites.
      These data also indicate that there may be marked species differences in the
      specificity of corticosteroid binding sites.

PMID- 10890569
TI  - Recombinant prolactin receptor extracellular domain of rainbow trout
      (Oncorhynchus mykiss): subcloning, preparation, and characterization.
AB  - The cDNA of the extracellular domain of rainbow trout (Oncorhynchus mykiss)
      prolactin receptor (trPRLR-ECD) was cloned in the prokaryotic expression vector
      pMON to enable its expression in Escherichia coli after induction with nalidixic
      acid. The bacterially expressed trPRLR-ECD protein, contained within the
      refractile body pellet, was solubilized in 4.5 M urea, refolded, and purified on
      a Q-Sepharose column, pH 8, by stepwise elution with NaCl. The bioactive
      monomeric 26-kDa fraction was eluted in 0.2 M NaCl, yielding 20 mg/2.5 L of
      induced culture. The purified protein was over 98% homogeneous, as shown by SDS
      PAGE in the presence or absence of reducing agent and by chromatography on a
      Superdex column. Binding experiments using [125I]ovine placental lactogen (oPL)
      as a ligand revealed that human growth hormone (hGH), oPL, and ovine prolactin
      (oPRL) were the most effective competitors, with respective IC50 values of 1.32,
      2.27, and 2.70 nM. Chicken (ch) PRL did not compete at all, and homologous trPRL
      was much less effective, with a corresponding IC50 value of 1826 nM. Gel
      filtration was used to determine the stoichiometry of trPRLR-ECD's interaction
      with oPL, hGH, and oPRL. Only oPL yielded a 2:1 complex, whereas hGH and oPRL
      formed only 1:1 complexes, with excess trPRLR-ECD being seen at the initial 2:1
      trPRLR-ECD:hGH or trPRLR-ECD:oPRL ratios. No studies were performed with chPRL
      because of its inability to compete with [125I]oPL or with trPRL because of its
      low affinity toward trPRLR-ECD. The present results agree with previous findings
      indicating, as in mammals, that homologous PRL interacts transiently with its
      receptor and suggest that transient homologous PRL-induced homodimerization of
      the receptor is sufficient to initiate a biological signal, despite the fact
      that, in classical binding experiments, only low specific binding can be
      detected.

PMID- 10890570
TI  - Sex-related differences in the effects of late winter pairing activity and
      seasonal influences on neuroendocrinology and gonadal development of mallards.
AB  - The importance of late winter pairing activity on the neuroendocrinology of wild
      waterfowl is unknown. In this study, we examined the sex-related differences in
      the roles of late winter pairing activity and seasonal influences on
      neuroendocrine and reproductive physiology in both male and female mallards. Our
      main goals were to determine (1) which physiological responses were influenced by
      pairing status or by seasonal changes and (2) whether responses differed between
      the sexes. Thus, physiological responses of mallards in different pairing status
      categories were assessed at two times: January 28 to February 5 and February 24
      to March 3. Ducks were assigned to one of the following pairing status
      categories: strong pairs, temporary pairs, unpaired or lone birds within the
      flock, or birds isolated in same-sex groups. Seasonal changes correlated with
      increases in both gonadal mass and hypothalamic content of vasoactive intestinal
      peptide in both sexes, whereas only pairing status correlated with changes in
      body mass in both sexes. The main sex-related differences were the following: (1)
      Seasonal decreases in hypothalamic gonadotrophin releasing hormone II content
      occurred only in females. (2) Seasonal increases in serum prolactin occurred only
      in males, whereas levels in females were low throughout the study. (3) Both male
      and female gonadal masses increased seasonally, but male gonadal mass was
      initially twice that of females. (4) Body mass of both sexes was influenced by
      pairing status correlations (i.e., all paired or lone birds were heavier than
      isolated birds), but body mass in males decreased seasonally. No sex-related
      differences occurred in hypothalamic gonadotrophin releasing hormone I content or
      circulating serum luteinizing hormone. Taken together, these results indicate
      that seasonal reproduction in mallards is regulated not only by seasonal but also
      by social cues, and differences occur between the sexes, months in advance of
      actual breeding.

PMID- 10890572
TI  - Gonadal source of testosterone metabolites in urine of male cotton-top tamarin
      monkeys (Saguinus oedipus).
AB  - Examining gonadal function in the small excitable cotton-top tamarin monkey
      (Saguinus oedipus) requires noninvasive sampling techniques. Two studies were
      performed to identify the quantifiable urinary metabolites of testosterone in
      cotton-top tamarins and which of the measurable metabolites would best reflect a
      gonadal source of testosterone secretion. In the first study, we injected
      unlabeled testosterone i.m. in males at either 500-ng or 1-microg levels. Urine
      samples were analyzed for androgens and estrogens. Testosterone and
      dihydrotestosterone (DHT) increased significantly following the injections in
      test males but not in control males. No significant increases in androstenedione
      occurred. Mean levels of estradiol and estrone did not consistently increase
      during the 5 days following injection. In the second study, a gonadotropin
      releasing hormone antagonist, Antide, was used to block LH stimulation of gonadal
      steroidogenesis. Males given Antide at either a 6 mg/kg dose or an 18 mg/kg dose
      showed significantly lower levels of urinary LH than controls. At the higher
      Antide dose, testosterone levels were significantly reduced during weeks 1 and 2
      posttreatment, whereas DHT levels significantly declined during the 2nd week
      posttreatment. Estradiol levels were highly variable prior to treatment but
      decreased significantly following treatment, whereas estrone levels remained
      variable throughout. These results indicate that measurement of urinary
      testosterone and possibly DHT reflect gonadal function in male cotton-top
      tamarins. Other sources of urinary estrogens may occur for the male cotton-top
      tamarin, but these data suggest that a substantial part of urinary estradiol is
      from gonadal sources, whereas urinary estrone appears to be mainly from
      extragonadal sources.

PMID- 10890571
TI  - Sex steroid levels across the reproductive cycle of female leopard geckos,
      Eublepharis macularius, from different incubation temperatures.
AB  - Incubation temperature during embryonic development determines gonadal sex in
      many reptiles, including the leopard gecko (Eublepharis macularius). In this
      study, we examined the hormonal and behavioral changes that occur during the
      reproductive cycle of female leopard geckos from four (i.e., 26, 30, 32.5, and 34
      degrees C) incubation temperatures. Controlling for reproductive status, plasma
      levels of dihydrotestosterone (DHT), testosterone (T), and progesterone (P)
      varied with incubation temperature but estradiol 17-beta (E2) levels did not.
      Controlling for the effects of incubation temperature, DHT and T levels were low
      when females were previtellogenic, increased slightly during early
      vitellogenesis, increased dramatically during late vitellogenesis (i.e., prior to
      ovulation), and then decreased to previtellogenic levels after ovulation. In
      contrast, E2 levels increased gradually from the previtellogenic stage to the
      early vitellogenic stage, peaked during late vitellogenesis, and decreased to
      previtellogenic levels after ovulation. Levels of P increased from the
      previtellogenic stage to the early vitellogenic stage, remained elevated during
      late vitellogenesis, and then decreased after ovulation. Moreover, we determined
      that females were not sexually receptive when previtellogenic, were somewhat
      receptive during early vitellogenesis (approximately 20% receptive), were most
      receptive during late vitellogenesis (approximately 80% receptive), and were
      again unreceptive after ovulation. Incubation temperature did not influence
      receptivity. Overall, these data show that hormone levels and behavior change
      coordinately during the reproductive cycle. Although incubation temperature has
      persistent effects on endocrine physiology in adult female leopard geckos, these
      effects are modest compared to hormonal changes across the reproductive cycle.

PMID- 10890573
TI  - Effects of melatonin on liver estrogen receptor and vitellogenin expression in
      rainbow trout: an in vitro and in vivo study.
AB  - Although melatonin is believed to mediate many seasonal and circadian effects of
      photoperiod on reproduction in salmonids, the precise mechanisms underlying such
      effects are still largely unknown. Recent data of the literature indicate a
      relationship between melatonin and expression of estrogen receptors (ER) in
      various tissues. In this study, the effects of melatonin on estrogen receptor
      and/or vitellogenin expression were studied by a combination of in vivo and in
      vitro experiments. In yeast stably expressing ER and transfected with an estrogen
      responsive element-beta-galactosidase reporter gene, melatonin had no effect on
      basal or E2-stimulated ER expression. Incubation of hepatocyte aggregates with
      melatonin (10(-8) to 10(-4)) for 16 or 48 h did not modify the E2-stimulated ER
      and vitellogenin mRNA, as measured by dot blots. Finally, neither pinealectomy
      nor melatonin implants caused any effect on basal or E2-stimulated ER and
      vitellogenin mRNA contents in the liver. Altogether, these results suggest that,
      although we cannot exclude potential effects at the brain or pituitary levels,
      melatonin has no or little effects on estrogen receptor in the liver.

PMID- 10890574
TI  - Widespread expression of the mRNA encoding a novel vitamin D/thyroxine dual
      binding protein in the turtle Trachemys scripta.
AB  - Vitamin D-binding protein (DBP) is the major transport protein for the vitamin D
      sterols in a variety of mammalian and avian species. The DBP found in the emydid
      family of turtles is unique in that it exhibits high-affinity binding of both
      vitamin D and thyroxine (D/TBP). Sequence analysis has revealed that the emydid
      D/TBP is homologous to mammalian DBP and shares no homology with mammalian
      thyroxine-binding globulins. Northern blot analysis was used to examine the
      spatial profile of D/TBP transcription in the turtle Trachemys scripta. In both
      adults and hatchlings, two transcripts--the expected 1.5-kb full-length
      transcript and a second 0.8-kb transcript--were present in nearly all of the
      tissues examined. In adults, highest expression of the 1.5-kb transcript was seen
      in the kidney, gonad, and spleen, with lower levels in the liver and lung and no
      transcripts in skeletal muscle. In hatchlings, the full-length transcript was
      detected in a variety of tissues at similar levels. Injection of hatchlings with
      thyroxine increased levels of circulating D/TBP and transcript levels. These data
      are in marked contrast to observations in mammals in which transcription of DBP
      is confined predominantly to the liver. Further, the increase in circulating
      D/TBP associated with increased thyroidal activity may result from a direct or
      indirect activation of D/TBP transcription by thyroxine.

PMID- 10890575
TI  - Selective estrogen receptor modulators in reproductive medicine and biology.
AB  - Estrogen replacement therapy has significant potential benefits for
      postmenopausal women, such as improvement of menopausal symptoms and protection
      from osteoporosis, but it may also increase a woman's risk of breast cancer.
      Also, some women do not take hormone replacement therapy because of such
      undesirable side effects as breast tenderness and uterine bleeding. Therefore,
      there is much interest in the development of compounds that provide the benefits
      of estrogen replacement therapy without the risks and side effects. The selective
      estrogen receptor modulators make up one class of compounds with both estrogen
      agonist and antagonist activity. This review discusses the clinical indications,
      risks, benefits, and mechanisms of action of selective estrogen receptor
      modulators and related compounds.

PMID- 10890576
TI  - Pharmacotherapy of nicotine dependence.
AB  - Withdrawal treatment of cigarette smokers is a task of the utmost urgency in view
      of the consequences for national health programs and legislative policies of the
      high morbidity and mortality rates caused by smoking. Smokers need medical
      consultation in addition to drug-based treatment, but this results in self-willed
      quitting of the smoking habit in a limited number of smokers only. From the point
      of view of the criteria of "evidence-based medicine", non-drug methods such as
      hypnosis therapy and acupuncture are not effective (odds ratio = 1.22). Among the
      drug-based methods, treatment with nicotine substitution preparations has shown
      confirmed efficacy in numerous studies (odds ratio 1.63 to 2.67, depending on the
      application form used) and results in successful withdrawal from the smoking
      habit in 30-40% of cases. A decisive problem in the initial therapeutic phase
      appears to be the amount of the applied nicotine dose, but beyond that can be
      mastered above all by combining 2 or 3 application forms (patchs, chewing gum,
      nasal spray). Treatment is then continued for 4-12 weeks, depending on the degree
      of dependence, with successively reduced nicotine dosage. Two controlled studies
      with disparate designs have been done on bupropion (odds ratio 2.3/3.0). However,
      further studies are desirable due to concern about undesirable effects of
      bupropion described recently. Other substances subjected to trials in years past,
      such as clonidine, lobeline, mecamylamine and antidepressants including buspirone
      cannot be recommended on the basis of current data for treatment of smokers
      seeking a withdrawal cure.

PMID- 10890578
TI  - Pharmacokinetics of cerivastatin when administered under fasted and fed
      conditions in the morning or evening.
AB  - OBJECTIVE: The influence of food and time of drug dosing on the pharmacokinetics
      of cerivastatin, a potent HMG-CoA reductase inhibitor, was evaluated in 24
      healthy male subjects between 21 and 44 years of age. METHODS: A single-dose,
      four-way crossover design was employed, with each subject receiving cerivastatin
      0.8 mg at weekly intervals under each of four conditions: 8 a.m. dosing after an
      overnight fast (reference), 8 a.m. dosing with a high-fat breakfast (test), 6
      p.m. dosing with the evening meal (low-fat; test), and 10 p.m. dosing 4 h after
      dinner (reference). Plasma concentrations of the parent compound and its active
      metabolites were measured by high performance liquid chromatography with
      fluorescence detection subsequent to post-column derivatization. RESULTS: The
      calculated 90% confidence intervals for cerivastatin AUC and Cmax were completely
      contained within the range 0.8 to 1.25. Thus, no relevant influence of food could
      be detected, although the presence of food increased the Cmax of cerivastatin on
      average by 12% (90% confidence interval: 1.04 - 1.21) under morning, but not
      evening dosing. With respect to the effect of daytime on cerivastatin
      pharmacokinetics, AUCs were bioequivalent for all treatment conditions, with Cmax
      values slightly lower (8 - 19%) following evening dosing, irrespective of food
      intake. Cerivastatin was well tolerated by the subjects in the study. CONCLUSION:
      Food effect bioequivalence according to current guidelines could be demonstrated.
      Cerivastatin can be administered independent of meal intake at dinner or at
      bedtime, the preferred time of dosing for statins because the rate of hepatic
      cholesterol synthesis is greatest at night.

PMID- 10890577
TI  - Population pharmacokinetics of digoxin in Korean patients.
AB  - AIM: Digoxin possesses a narrow therapeutic index and shows a large inter-patient
      pharmacokinetic variability. The purpose of this study was to develop a
      population model for the pharmacokinetics of digoxin in Korean patients. METHODS:
      Plasma concentrations of digoxin after multiple administration at varying dosing
      schedules in Korean patients were used for population modeling. Data analysis was
      performed with the P-Pharm software. The data were best fitted by a one
      compartment model. The effect of demographic and clinical factors like sex, age,
      weight, disease state, and renal function on the pharmacokinetic parameters of
      digoxin was investigated. RESULTS: The study indicated that the clearance of
      digoxin was influenced by creatinine clearance, while body weight and creatinine
      clearance were the covariates for its volume of distribution. The population mean
      estimates for CL and V were 4.4 l/h and 535 l, respectively. Absorption rate
      constant was lower in females and in the presence of concomitant drug treatment.
      CONCLUSION: A population pharmacokinetic model for the digoxin pharmacokinetics
      in a section of Korean patients was developed. The relationships between the
      pharmacokinetic parameters and the demographic data and the patient-specific
      covariates were established.

PMID- 10890579
TI  - Natriuretic effect of barnidipine, a long-acting dihydropyridine calcium channel
      blocker, in patients with essential hypertension.
AB  - OBJECTIVE: To evaluate the effect of barnidipine hydrochloride, a long-acting
      dihydropyridine calcium channel blocker on urinary sodium excretion in patients
      with essential hypertension. PATIENTS: Twelve patients (2 males, 10 females) with
      mild to moderate essential hypertension. METHODS: A single-blinded study. After
      the control (placebo) period, 10 to 15 mg barnidipine hydrochloride was
      administered for 7 days, followed by a post-treatment (placebo) period. Daily
      changes in blood pressure, urinary volume, and urinary electrolyte excretions
      were evaluated. Plasma levels of atrial natriuretic peptide (ANP) and aldosterone
      were also determined in each period. Daily sodium intake was kept at 120 mEq.
      RESULTS: Blood pressure decreased from 161 +/- 4/92 +/- 2 mmHg to 146 +/- 4/85 +/
      2 mmHg (p<0.05) after 7-day-treatment with barnidipine. Barnidipine
      significantly increased urinary sodium excretion; the change was evident on the
      first day of administration (control period 41 +/- 3 mEq/day, and first day 59 +/
      3 mEq/day, p < 0.05). Drug discontinuation transiently decreased sodium
      excretion to 35 +/- 3 mEq/day. Cumulative sodium balance after 7-day-treatment
      reached 47 +/- 19 mEq. Urine volume, potassium excretion, and creatinine
      excretion did not change during the treatment period. The plasma levels of ANP
      tended to increase, but those of aldosterone did not change with barnidipine.
      CONCLUSION: Barnidipine administration for a week decreased the blood pressure
      and made the sodium balance negative by increasing the urinary sodium excretion
      in patients with essential hypertension. The natriuretic effect of this drug
      could contribute at least in part to its antihypertensive effect.

PMID- 10890580
TI  - Relative bioavailability study of two nifedipine tablet formulations in healthy
      male volunteers.
AB  - OBJECTIVE: To assess the bioequivalence of two oral formulations containing 10 mg
      of nifedipine. The test preparation were Macorel tablets, the reference
      preparation were Adalat tablets. SUBJECTS, MATERIAL AND METHODS: The study was
      designed as a single-dose, three-period crossover randomized design to 18 non
      smoker, healthy male volunteers under fasting conditions. Seventeen volunteers
      completed the study. Plasma samples were analyzed for nifedipine by HPLC after
      solid-phase extraction. The pharmacokinetic parameters used to assess the
      bioequivalence of the two formulations were AUC(0-infinite) and AUC(0-t) for the
      extent of absorption and Cmax and Tmax for the rate of absorption. Statistical
      comparisons of AUC(0-infinite) AUC(0-t), and Cmax data were evaluated after
      logarithmic transformation by two-way analysis of variance (ANOVA), and
      differences of Tmax were tested non-parametricaly. RESULTS: Point estimates (90%
      confidence intervals) of the test/reference ratios were 97.4% (87.6%-108.3%) for
      AUC(0-infinite) 97.0% (85.6%-110.1%) for AUC0-t, and 107.7% (89.1%-130.7%) for
      Cmax. No statistically significant difference was found for Tmax and elimination
      half-life values. CONCLUSION: Therefore, in accordance with the European Union
      bioequivalence requirements, the test and reference nifedipine preparations are
      bioequivalent for both the extent and the rate of absorption.

PMID- 10890581
TI  - Aspirin esterases in North-West Indians: the influence of age and nutrition.
AB  - OBJECTIVE: To determine the activity of aspirin esterases in North-West Indian
      population and to find the effect of age and nutrition on it. SUBJECTS, MATERIAL
      AND METHODS: The serum albumin, plasma cholinesterase (PChE), aspirin esterase
      (ASPES) and phenyl acetate esterase (PAE) were determined in 175 subjects: young
      (< 40 years) and healthy (BMI > 19) = 74; elderly (> 50 years) and healthy (BMI >
      19) = 32; young (< 40 years) and emaciated (BMI < 19) = 44; elderly (> 50 years)
      and emaciated (BMI < 19) = 25). RESULTS: The serum albumin levels significantly
      decreased with increase in age (r = -0.384, p < 0.01) and with decrease in body
      mass index (r = 0.457, p < 0.01). When the activity of esterases in four groups
      was compared, the PAE activity was not found to be affected by age or nutrition
      and the ASPES and PChE activity were significantly lower only in elderly
      emaciated (p < 0.01). CONCLUSION: As elderly emaciated have decreased serum
      albumin, ASPES and PChE activity, they may need a lower dose of aspirin to
      achieve the desired antiplatelet and analgesic effect. The young emaciated
      subjects, in spite of their lower serum albumin levels, may not require a lower
      dose of aspirin.

PMID- 10890582
TI  - Effect of three different diets on the bioavailability of a sustained release
      lithium carbonate matrix tablet.
AB  - BACKGROUND: Food-induced changes on the bioavailability of a sustained release
      lithium carbonate matrix tablet, which uses an acrylic matrix of Eudragit RSPM as
      sustaining agent, have been studied in healthy male volunteers. The tablet was
      developed in our laboratory using conventional technology. SUBJECTS, MATERIALS
      AND METHODS: The study design was a 4 x 4 Latin square involving 12 subjects who
      received a single dose of the tablet while fasting or with a standardized normal,
      high fat or high fat/high protein meal. RESULTS: The results showed no
      differences in half-lifebeta, renal clearance, Vdbeta, AUC, tmax, Xinfinite(u),
      fraction absorbed and MRT. Higher Cmax (mg/l) were obtained when the tablet was
      administered with any kind of meal: 2.09 +/- 0.47 (fast), 2.95 +/- 1.04 (normal
      diet), 2.64 +/- 0.54 (high fat diet) and 2.87 +/- 0.67 (high fat/high protein
      diet). The analysis of the ratio Cmax/AUC indicated that changes in Cmax were
      more probably due to changes in the rate of absorption. To evaluate if the
      magnitude of the change could be clinically relevant, Cmax and C at 12 hours
      (dosing interval) were treated by the superposition method in order to establish
      maximum and minimum concentrations at steady-state. For all the experimental
      conditions both concentrations would remain in the therapeutic range (4.2 10 mg/l
      or 0.6 - 1.4 mEq/l). CONCLUSION: The behavior of the formulation is appropriate
      for a sustained release tablet and fasting or non-fasting state seems not to be a
      major consideration for bioavailability when deciding on the regimen
      administration.

PMID- 10890583
TI  - Cognitive style: problem solving by rhesus macaques (Macaca mulatta) reared with
      living or inanimate substitute mothers.
AB  - Cognitive style, reflected in the generation of novel solutions and the use of
      identifiable response strategies in problem-solving situations, was contrasted in
      rhesus monkeys (Macaca mulatta) reared individually with either canine companions
      or inanimate surrogate mothers. Four experiments were conducted over a 5-year
      period, examining problem solving in relatively unstructured as well as more
      formal situations. Results indicated that whereas the 2 rearing groups did not
      differ on most measures of performance, consistent response strategies were
      identified for the dog-raised monkeys. The results were compared with previously
      published data from the same monkeys demonstrating rearing group differences in
      abilities to engage in complex social interaction. The animate nature of the
      early rearing environment may facilitate-the development of a cognitive style
      that influences problem-solving abilities in both the social and nonsocial
      realms.

PMID- 10890584
TI  - Chimpanzee (Pan troglodytes) handedness: variability across multiple measures of
      hand use.
AB  - This study examined intertask consistency in handedness across multiple measures
      of hand use in a sample of 187 chimpanzees (Pan troglodytes). Hand preferences
      for 2 to 6 measures were collected from the sample, and hand preference scores
      were derived on the basis of the individual hand preferences for each measure.
      Seven of 15 possible intratask correlations were significant, with some degree of
      clustering depending on the motor demands of the tasks. Two overall measures of
      handedness revealed population-level right-handedness in the chimpanzees,
      although the degree of bias was reduced for chimpanzees tested on more than 3
      measures of hand use. The results are interpreted in the context of several
      recent studies that proposed theoretical models of handedness in nonhuman
      primates.

PMID- 10890585
TI  - Estimating and operating on discrete quantities in orangutans (Pongo pygmaeus).
AB  - This study investigated the ability of 3 male orangutans (Pongo pygmaeus; 1
      subadult, 2 adults) to estimate, compare, and operate on 2 sets of small
      quantities (1-6 cereal bits). Experiment 1 investigated the orangutans' ability
      to choose the larger of 2 quantities when they were presented successively as
      opposed to simultaneously, thus being perceptually unavailable at the time of
      choice. Experiment 2 investigated the orangutans' ability to select the larger
      quantity after the original quantities were augmented or reduced. Orangutans were
      capable of selecting the larger of 2 quantities in Experiment 1. There was also
      some evidence from Experiment 2, albeit weaker, that orangutans may mentally
      combine quantities (but not dissociate) to obtain the larger of 2 quantities.
      This study suggests that orangutans use a representational mechanism (especially
      when comparing quantities) to select the larger of 2 sets of items.

PMID- 10890586
TI  - Development of object permanence in food-storing magpies (Pica pica).
AB  - The development of object permanence was investigated in black-billed magpies
      (Pica pica), a food-storing passerine bird. The authors tested the hypothesis
      that food-storing development should be correlated with object-permanence
      development and that specific stages of object permanence should be achieved
      before magpies become independent. As predicted, Piagetian Stages 4 and 5 were
      reached before independence was achieved, and the ability to represent a fully
      hidden object (Piagetian Stage 4) emerged by the age when magpies begin to
      retrieve food. Contrary to psittacine birds and humans, but as in dogs and cats,
      no "A-not-B error" occurred. Although magpies also mastered 5 of 6 invisible
      displacement tasks, evidence of Piagetian Stage 6 competence was ambiguous.

PMID- 10890587
TI  - Summation of symbols by pigeons (Columba livia): the importance of number and
      mass of reward items.
AB  - In each of 3 experiments, different sets of 4 pigeons (Columba livia) were
      trained to discriminate between 2 visual symbols that covered wells containing
      food items that varied in number, mass, or both. In Experiment 1, the symbols
      were associated with 0, 1, 3, 5, 7, or 9 pieces of grain reward. The pigeons
      learned to choose the symbol corresponding to the larger reward, and on summation
      tests, they chose the pair of symbols that summed to the larger total reward.
      When number of food pellets was varied but mass of reward was held constant in
      Experiment 2, preference for the larger number symbols failed to appear. When
      number was held constant and mass was varied in Experiment 3, the pigeons showed
      a clear preference for the larger mass symbols on single-symbol and summation
      tests. These findings show that pigeons summate the value of symbols and are more
      likely to represent symbols by mass of food reward than by number of food items.

PMID- 10890588
TI  - Perception of mistuned harmonics in complex sounds by the bullfrog (Rana
      catesbeiana).
AB  - The ability of 73 male bullfrogs (Rana catesbeiana) to detect single mistuned
      harmonics in an otherwise periodic signal was studied. Bullfrogs in their natural
      environment were presented with playbacks of synthetic signals, resembling their
      species advertisement calls, that differed in the frequency of 1 harmonic
      component (out of 22). There were significant differences in the number and
      latency of the males' evoked vocal responses to these stimuli, suggesting that
      males were sensitive to the differences between the sounds. Differences in
      envelope shape (rate and depth of amplitude modulation) produced by the harmonic
      mistunings may underlie the differences in response. Frogs, like birds and
      humans, can discriminate sounds on the basis of harmonic structure, indicating
      that this is a general perceptual trait shared among vertebrates.

PMID- 10890589
TI  - Auditory scene analysis in estrildid finches (Taeniopygia guttata and Lonchura
      striata domestica): a species advantage for detection of conspecific song.
AB  - Operant-conditioning techniques were used to investigate the ability of zebra
      finches (Taeniopygia guttata) and Bengalese finches (Lonchura striata domestica)
      to detect a zebra finch or a Bengalese finch target song intermixed with other
      birdsongs. Sixteen birds were trained to respond to the presence of a particular
      target song, either of their own species (n = 8) or of another species (n = 8).
      The birds were able to learn a discrimination between song mixtures that
      contained a target song and song mixtures that did not, and they were able to
      maintain their response to the target song when it was mixed with novel songs.
      Zebra finches, but not Bengalese finches, learned the discrimination with a
      conspecific target more quickly and were worse at detecting a Bengalese finch in
      the presence of a conspecific song. The results indicate that selective attention
      to birdsongs within an auditory scene is related to their biological relevance.

PMID- 10890590
TI  - Maternal behavior, paternal behavior, and pup survival in CD-1 albino mice (Mus
      musculus) in three different housing conditions.
AB  - Parental behavior, food consumption, and pup development in litters of CD-1
      albino mice (Mus musculus) with single mothers or paired mothers in 3 different
      housing conditions were compared. Fewer pups survived when parents were required
      to run in a wheel to obtain food, and these pups had lower weights than pups in
      the wheel-noncontingent and no-wheel groups. The presence of the male facilitated
      pup survival in the wheel-contingent group but had no effect on pup growth. Mice
      in the wheel-contingent group ran more revolutions than those in the wheel
      noncontingent group and spent less time in parental care. In the wheel-contingent
      group, males spent more time running and ate less food than females, suggesting
      that males may indirectly facilitate pup development by providing food for the
      mother. The results suggest that the presence of the male increases pup care and
      may facilitate maternal behavior under appropriate environmental conditions.

PMID- 10890591
TI  - Pain sensitivity and individual differences in self-reported sexual behavior.
AB  - The relationship between sexual behavior and pain sensitivity was assessed in 27
      heterosexual men and 20 heterosexual women. Sexual behavior measures included
      sexual motivation and ratings of subjective sexual arousal to and enjoyment of an
      auditory stimulus. Pain sensitivity measures were pain threshold and pain
      tolerance in a cold pressor task. Participants were tested after exposure to a
      neutral or a sexual audio stimulus. Exposure to the sexual stimulus increased
      pain sensitivity in women but not in men. However, sexual behavior measures were
      correlated with pain threshold for both men and women. Specifically, higher pain
      thresholds were associated with weaker sexual motivation, lower enjoyment
      potential for sexual interaction, and increased inhibition during intercourse.
      These results are consistent with findings in laboratory animals, suggesting that
      differences in sexual behavior may reflect differences in responsiveness to a
      variety of stimuli.

PMID- 10890592
TI  - Learning and limits of use of eye gaze by capuchin monkeys (Cebus apella) in an
      object-choice task.
AB  - The ability of 3 capuchin monkeys (Cebus apella) to use experimenter-given cues
      to solve an object-choice task was assessed. The monkeys learned to use explicit
      gestural and postural cues and then progressed to using eye-gaze-only cues to
      solve the task, that is, to choose the baited 1 of 2 objects and thus obtain a
      food reward. Increasing cue-stimulus distance and introducing movement of the
      eyes impeded the establishment of effective eye-gaze reading. One monkey showed
      positive but imperfect transfer of use of eye gaze when a novel experimenter
      presented the cue. When head and eye orientation cues were presented
      simultaneously and in conflict, the monkeys showed greater responsiveness to head
      orientation cues. The results show that capuchin monkeys can learn to use eye
      gaze as a discriminative cue, but there was no-evidence for any underlying
      awareness of eye gaze as a cue to direction of attention.

PMID- 10890593
TI  - The relationship between prosthetics and orthotics services and community-based
      rehabilitation. A joint ISPO/WHO statement October 1999.

PMID- 10890594
TI  - Factors affecting wound healing after major amputation for vascular disease: a
      review.

PMID- 10890595
TI  - Relative mortality and long term survival for the non-diabetic lower limb amputee
      with vascular insufficiency.
AB  - On a well defined non-diabetic amputation group with vascular insufficiency
      consisting of 10,191 amputations during the period 1982 to 1992 the Standard
      Mortality Rate (SMR) and the long term survival (Kaplan-Meyer) were analysed. The
      SMR for the total group was 8.6 (8.4-8.9) times the expected mortality the first
      year after amputation, decreasing to 3.2 (3.3-3.4) the second year. SMR in
      relation to age, gender and level of amputation was analysed. In the long term
      survival studies the median survival time (50% survival) for the total group was
      1.8 years. Significant relation was found between the long term survival and
      gender, age and level of amputation.

PMID- 10890596
TI  - Prevalence and causal conditions for amputation surgery in the third world: ten
      years experience at Dodoma Regional Hospital, Tanzania.
AB  - This is a partly retrospective study of 252 major limb amputations carried out in
      regional hospital in Tanzania over a period of ten years mostly by the authors.
      The paper reports on the aetiology and levels of amputation and identifies
      prevalence and sex of the amputees. The causes of amputation classified under
      tumours, vascular diseases, trauma, infections, burns, animal bites, iatrogenic
      causes, maduromycosis and miscellanea--are discussed with particular reference to
      the influence of the environment, cultural habits and local customs.

PMID- 10890597
TI  - A new alignment jig for quantification and prescription of three-dimensional
      alignment for the patellar-tendon-bearing trans-tibial prosthesis.
AB  - Clinically, it is hard to achieve and reproduce prosthesis alignment at will
      during daily prosthesis fitting. A new alignment jig was designed and developed
      to facilitate quantification and prescription of prosthesis alignment for
      patellar-tendon-bearing (PTB) trans-tibial prostheses. The alignment jig provided
      instantaneous readings of the three-dimensional orientation and position of the
      socket relative to the prosthetic foot in standardised units. The inter- and
      intra-tester errors of the alignment jig in measuring prosthesis alignment were
      evaluated and demonstrated to have good reliability. The alignment jig was
      recommended to be used clinically after the conventional dynamic alignment
      procedure to document the prosthesis alignment. Further application of the
      alignment jig for systematic evaluation of the effects of prosthesis alignment on
      gait for trans-tibial amputees is suggested.

PMID- 10890598
TI  - Effects of sagittal plane prosthetic alignment on standing trans-tibial amputee
      knee loads.
AB  - The influence of sagittal plane prosthetic alignment changes on loads applied to
      the ispilateral knee was investigated using 5 transtibial amputee subjects. The
      goal was to determine which prosthetic alignment results in the most energy
      efficient standing and also minimises stresses on knee structures during
      standing. The electromyogram, the external mechanical loading of the prosthetic
      leg and the amputees' posture were recorded for a wide range of prosthetic
      alignments. The EMG of the vastus lateralis and biceps femoris muscles was
      measured bilaterally; the EMG of the gastrocnemius muscle was measured only on
      the contralateral side. The distance between the anatomical knee centre and each
      individual's load line, as determined by the Otto Bock "L.A.S.A.R. Posture"
      alignment system, was used as a measure of the mechanical load applied to the
      knee joint. Prosthetic alignment has almost no influence on muscle activity of
      the contralateral lower limb during static standing. On the other hand,
      prosthetic alignment has a significant influence on the load applied to the
      amputee's ipsilateral knee joint. The external knee moments applied to the knee
      ligaments and knee muscles on the amputated side change systematically in
      response to different plantar flexion or dorsiflexion angles of the prosthetic
      ankle-foot. During standing the extensor muscles stabilise the limb by
      contracting if the load line is located less than 15 mm anterior to the
      anatomical knee centre. The biceps femoris muscle appears to have little or no
      protective function against hyperextension during standing even if large external
      knee extension moments are caused by excessive plantar flexion. Such extreme
      alignments significantly increase the stresses on knee ligaments and the
      posterior knee capsule. When prosthetic sagittal plane alignment is altered, the
      trans-tibial amputee compensates by balancing the upper part of the body over the
      centre of pressure of the prosthetic foot. Biomechanically optimal alignment of
      the trans-tibial prosthesis occurs when the individual load line is approximately
      15 mm anterior to the anatomical knee centre, permitting a comfortable, energy
      efficient standing and minimising the mechanical loading on the knee structures.

PMID- 10890599
TI  - A survey of function in children with lower limb deficiencies.
AB  - Function and prosthesis technical problems were surveyed in 258 experienced
      paediatric lower-limb prosthesis wearers. The two-part survey form consisted of
      the modified Prosthesis Evaluation Scale and the core module of the American
      Academy of Orthopaedic Surgeons/Council of Musculoskeletal Specialty Societies
      (AAOS/COMSS) Lower Limb Outcomes instrument. Eighty-eight percent (88%) of these
      paediatric subjects were able to wear their prosthesis more than 9 hours/day;
      only 3 subjects (1%) were not able to wear their limb at all. The average
      distance walked per day was reported to be 5.24 kilometres. Sixteen percent (16%)
      reported pain as "moderate" or worse. A majority reported not having a problem
      with perspiration, however, 20% had problems serious enough to limit prosthesis
      wearing time significantly. The most common reasons for temporary loss of limb
      use were pain (62 responses) and prosthesis failure (59 responses), followed by
      tissue breakdown (42 responses) and perspiration (30 responses). In general, the
      paediatric population achieves full use at a high rate, is much more active than
      the adult population, and experiences less limb pain.

PMID- 10890600
TI  - Preliminary experiences with modified SACH feet manufactured and used in a
      tropical developing world setting.
AB  - In a prospective study of polypropylene (PP) prostheses for trans-tibial amputees
      four different modified SACH feet were used. These are identified as: 1. BAVI
      from the national manufacturer of componentry in BaVi; 2. HCMC a design initiated
      by the International Committee of the Red Cross (ICRC) together with the Army
      Factory in Ho Chi Minh City; 3. HI from Handicap International; 4. VI from
      Veterans International, Cambodia. Four (4) from 5 BAVI feet, 7 from 9 HCMC feet
      and 4 from 10 HI feet failed after about a year on average, whereas none of 10 VI
      feet had failed after 19 months. Dimensional differences in the ankle part and in
      the height of the foot in the different designs made interchangeability
      impossible.

PMID- 10890601
TI  - Evaluation of use and durability of polypropylene trans-tibial prostheses.
AB  - Forty-three (43) trans-tibial prostheses with a mean period of use of 33 months
      were evaluated in terms of utilisation and durability. The majority of the
      prostheses (80%) were worn by amputees with demanding occupations, such as
      farmers, fishermen and tradesmen. The prostheses were in use approximately 9
      hours per day. No major or frequent breakdowns of the polypropylene prosthetic
      components were found. The suspension belts were the parts most frequently
      affected; a total of 32 needed replacement after an average 11 months of use.
      Eleven (11) prostheses were completely replaced, more than half at least partly
      because of socket-fitting problems. In all, socket-fitting problems were found in
      15 prostheses, causing pain and consequently limitation of use. While the
      prosthetic polypropylene components were satisfactory, the rubber foot was a
      major cause of early breakdown. A total of 40 feet were replaced; their mean
      period of use before breakdown was 9 months. In practice, parts were frequently
      replaced at a later stage than desirable, meaning that there was frequent
      "overuse" of prostheses with worn parts. Measures were taken to increase the life
      span of the prosthesis: change in the design of the foot; issuing a spare foot
      with the prosthesis; strengthening the suspension belt. Additional evaluations
      are necessary to confirm the degree to which the findings are representative.

PMID- 10890602
TI  - The use of the shuttle lock system for problem trans-femoral suspension.

PMID- 10890603
TI  - Reduction of skin problems at the Alpha socket/skin interface.
AB  - Two cases are presented in whom the provision of an Alpha Liner relieved the
      patients' stump discomfort but developed a skin eruption at the top of the liner.
      This was resolved satisfactorily by cutting scallops into the top of the liner.

PMID- 10890604
TI  - Comparative trials on hybrid walking systems for people with paraplegia: an
      analysis of study methodology.
AB  - A new orthosis (SEPRIX) which combines user friendliness with low energy cost of
      walking has been developed and will be subject to a clinical comparison with
      conventional hip-knee-ankle-foot orthoses. In designing such comparative trials
      it was considered it may be worthwhile to use previous clinical studies as
      practical examples. A literature search was conducted in order to select all
      comparative trials which have studied two walking systems (hip-knee-ankle-foot
      orthoses) for patients with a complete thoracic lesion. Study population,
      intervention, study design, outcome measurement and statistical analyses were
      examined. Statistical power was calculated where possible. Of 12 selected
      studies, 7 were simple A-B comparisons, 2 A-B comparisons with a replication, 2
      cross-over trials and 1 nonrandomised parallel group design, the last of which
      was considered internally invalid due to severe confounding by indication. All A
      B comparisons were considered internally invalid as well, since they have not
      taken into account that a comparison of two orthoses requires a control for
      aspecific effects (like test effects) which may cause a difference. Statistical
      power could only be examined in 4 studies and the highest statistical power
      achieved in one study was 47%. It is concluded that statistical power was too low
      to be able to detect differences. Even analysis through interval estimation
      showed that the estimation of the difference was too imprecise to be useful.
      Since the majority of the surveyed papers have reported small studies (of only 4
      6 patients), it is assumed that lack of statistical power is a more general
      problem. Three possibilities are discussed in order to enhance statistical power
      in comparative trials, i.e. multicentre studies, statistical pooling of results
      and improving the efficiency of study design by means of interrupted time series
      designs.

PMID- 10890605
TI  - Mechanical efficacy of the mobilising cervical support device (Mbrace).
AB  - This study evaluated the mechanical efficacy of a new "mobilising" cervical
      support device. This device has been developed in response to the requirements of
      whiplash patients to overcome the problems of heat and immobilisation which can
      occur in patients wearing conventional wrap-around cervical collars. All planes
      of cervical range of motion of 21 volunteer subjects without current or past
      cervical dysfunction were measured actively and passively under two conditions
      (no support and with cervical support) using the cervical range of motion (CROM)
      instrument. The results show that the mobilising cervical support device
      restricts hyperextension effectively while allowing substantial movement in other
      planes of motion (flexion, rotation and lateral bending). This potential mobility
      keeps nearly all muscles in the neck fit and problems of muscle atrophy, weakness
      and contraction, which can occur in patients using conventional cervical wrap
      around collars, can be avoided. Regarding mechanical efficacy, the mobilising
      cervical support device can be useful in the (early) mobilisation phase in
      patients needing gentle neck support after a soft tissue hyperextension or
      whiplash injury.

PMID- 10890606
TI  - Role of CuZn superoxide dismutase in regulating lymphocyte apoptosis during
      sepsis.
AB  - OBJECTIVE: The lymphocyte is a principal mediator of the inflammatory response,
      and lymphocyte depletion via apoptosis may be an important mechanism of
      modulating inflammation. Increased oxygen consumption occurs during sepsis and
      results in the generation of reactive oxygen species. Although reactive oxygen
      species initiate apoptosis in many biological systems, their role in controlling
      lymphocyte apoptosis during sepsis is unclear. The objective of this study was to
      better characterize the role of oxidative stress in precipitating lymphocyte
      apoptosis during sepsis and to specifically define the role of the CuZn
      superoxide dismutase (SOD) enzyme complex, a major antioxidant defense, in
      modulating this process. DESIGN: Prospective, randomized, controlled study.
      SETTING: Research laboratory at an academic medical center. SUBJECTS: Mice that
      were either genetically normal or that were deficient in or overexpressed the
      enzyme CuZn SOD. INTERVENTIONS: Mice from each genetic group were randomized to
      no manipulation (control), sham surgery, or cecal ligation and puncture. Mice
      were killed 18-24 hrs after study entry, and the thymi and spleen were removed
      for analysis of apoptosis. MEASUREMENTS AND MAIN RESULTS: Lymphocyte apoptosis
      was assessed by three independent methods: light microscopy, fluorescent terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labeling, and DNA gel electrophoresis. Comparisons were performed using standard
      parametric statistical tests. Lymphocyte apoptosis was present in mice after CLP
      but not in control mice or in mice after sham surgery (p < .05). Mice completely
      lacking CuZn SOD developed significantly more lymphocyte apoptosis than did
      either partially CuZn SOD-deficient or genetically normal mice (p < .05). This
      apoptosis was more pronounced in the thymus than the spleen and, within the
      thymus, more prominent in the cortex than medulla (p < .05 for all). In contrast,
      mice that overexpressed CuZn SOD did not differ in the amount of apoptosis after
      CLP compared with genetically normal mice (p = NS for all). CONCLUSIONS:
      Oxidative stress occurs in sepsis and appears to be one stimulus for the
      development of lymphocyte apoptosis, a process that is partly regulated by CuZn
      SOD. However, we were unable to demonstrate that overexpression of this enzyme
      suppressed lymphocyte apoptosis, suggesting that either other antioxidant
      defenses or other pathways independent of oxidative stress may mediate lymphocyte
      elimination in this syndrome.

PMID- 10890607
TI  - Observations of withdrawal of life-sustaining treatment from patients who became
      non-heart-beating organ donors.
AB  - OBJECTIVE: Non-heart-beating organ donation for transplantation is increasing
      despite the concern whether all the donors are dead. This concern is based on the
      adequacy of documentation of death and the appropriate duration that circulation
      and respiration should be absent before death certification. No studies have
      examined the documentation and deaths of patients who became non-heart-beating
      organ donors. DESIGN: Retrospective study of observational data. PATIENTS: All
      non-brain-dead patients who became non-heart-beating organ donors at the
      University of Pittsburgh Medical Center from January 1, 1993, to June 30, 1998,
      were identified. Records for 15 of 16 patients were available for review.
      MEASUREMENTS AND MAIN RESULTS: Adequacy of documentation, extubation time, onset
      of severe hypotension, duration of absent circulation before death was certified,
      and the time of incision for organ procurement were ascertained. Twelve of 15
      records had all required clinical documentation. The mean age of patients was
      46.5 +/- 5.7 yrs. All 15 patients were extubated before death and had femoral
      arterial catheters; one had a biventricular assist device discontinued. The time
      of hypotension and pulselessness was not documented for one and three patients,
      respectively. All 12 patients with documentation had > or =2 mins of absent
      circulation. Time from certification to incision for procurement was 1.1 +/- 2.3
      mins. CONCLUSIONS: In a small study of non-heart-beating organ donation,
      circulation never resumed after >1 min of absent circulation, suggesting that 2
      mins of absent circulation is sufficient to certify death. Three of 15 patients
      had inadequate documentation. Gaps and inconsistencies in documentation may raise
      concern about the potential for abuse.

PMID- 10890608
TI  - Shortening of cardiac action potentials in endotoxic shock in guinea pigs is
      caused by an increase in nitric oxide activity and activation of the adenosine
      triphosphate-sensitive potassium channel.
AB  - OBJECTIVE: To investigate the roles of nitric oxide and adenosine triphosphate
      (ATP)-sensitive potassium channels (KATP) in the shortening of cardiac action
      potential in endotoxic shock. DESIGN: Prospective animal study with concurrent
      controls. SETTING: University animal research laboratory. SUBJECTS: Adult Hartley
      guinea pigs, weighing 300-400 g. INTERVENTIONS: Guinea pigs were anesthetized and
      mechanically ventilated for 6 hrs. Lipopolysaccharide (LPS) or saline (sham
      group) were given intravenously. Drug effects were examined at the end of 6 hrs.
      MEASUREMENTS AND MAIN RESULTS: Plasma nitrate concentration was measured hourly,
      while guanosine 3',5'-cyclic monophosphate (cGMP) content and action potential
      duration at 90% of repolarization (APD90) of papillary muscle were examined every
      2 hrs in the 6-hr endotoxemia in both the sham and the LPS-treated groups. The
      basal levels of these three variables showed no difference in the two groups. In
      the sham group, these variables did not change significantly (n = 14 for plasma
      nitrate determination; n = 5 for cGMP content measurement; n = 5-14 for APD90
      measurement; all p > .05). But in the LPS-treated group, both plasma nitrate
      concentration and cGMP content of papillary muscle showed time-dependent
      increases and they were significantly higher than those in the sham group (at the
      6th hr, plasma nitrate: 42.6 +/- 7.7 vs. 21.8 +/- 3.1 micromol/L, both n = 14, p
      < .01; cGMP: 1.52 +/- 0.15 vs. 0.73 +/- 0.08 pmol/mg protein, both n = 5, p <
      .01). In contrast, APD90 revealed a time-dependent decrease compared with that in
      the sham group (at the 6th hr, 137.1 +/- 52 vs. 188.2 +/- 4.8 msecs, both n = 14,
      p < .001). In the following 60-min in vitro recording of action potentials after
      the end of 6-hr endotoxemia, the shortened APD90 in the LPS-treated group did not
      recover and remained shorter compared with that in the sham group, in which the
      APD90 showed no significant changes (at the 60th min, 165.1 +/- 5.7 vs. 200.2 +/-
      3.8 msecs, each n = 14, p < .01). However, in the presence of glibenclamide, a
      specific KATP blocker (100 micromol/L; n = 10), the APD90 could be reversed
      almost completely to the same value as that in the sham group (n = 14) (196.6 +/-
      3.5 vs. 200.2 +/- 3.8 msecs; p > .05), despite glibenclamide having no effect on
      the APD90 in the sham group. In the LPS-treated group, NG-nitro-L-arginine methyl
      ester (1 mmol/L; n = 4), methylene blue (10 micromol/L; n = 5), and
      aminoguanidine (100 micromol/L; n = 4) significantly prolonged the shortened
      APD90 (192.5 +/- 3.1, 195.0 +/- 3.3, and 176.5 +/- 3.3 msecs, respectively; p <
      .01, p < .01, and p < .05, respectively, compared with that without these agents,
      165.1 +/- 5.7 msecs, n = 14). These agents had negligible effects on the APD90 in
      the sham group (all p > .05). Furthermore, 8-bromoguanosine-3',5'-cyclic
      monophosphate (500 micromol/L; n = 5) decreased APD in intact papillary muscle
      (mean reduction of APD90, 13.5 +/- 3.5%, n = 5; p < .05), an effect abolished by
      pretreatment with glibenclamide (100 micromol/L; n = 5) that did not have an
      effect by itself. CONCLUSIONS: In this experimental model, we provide reasonably
      convincing evidence to suggest that in endotoxic shock, an increase in nitric
      oxide activity may activate KATP, which plays a major role in the shortening of
      APD, presumably through a cGMP-dependent pathway.

PMID- 10890609
TI  - Cardiopulmonary bypass decreases cytokine production in lipopolysaccharide
      stimulated whole blood cells: roles of interleukin-10 and the extracorporeal
      circuit.
AB  - OBJECTIVE: To determine whether cardiopulmonary bypass (CPB) alters the ex vivo
      cytokine production of whole blood cells stimulated by lipopolysaccharide (LPS)
      and to assess the roles of interleukin (IL)-10 and an extracorporeal circuit
      (ECC) in the alteration. DESIGN: Prospective, controlled study. SETTING:
      Biochemistry laboratory and surgical intensive care unit in a university
      hospital. PATIENTS: Seventeen consecutive adult patients undergoing coronary
      artery bypass grafting or valve surgery with normothermic CPB and eight healthy
      volunteers. INTERVENTIONS: Blood samples for cytokine measurement were drawn from
      patients before and during (at 60, 90, 120, 180 and 360 mins) CPB and were
      cultured with and without LPS and with and without anti-IL-10 antibodies. Blood
      was also drawn from healthy subjects and sampled for cytokine analysis before and
      during circulation in an isolated ECC. MEASUREMENTS AND MAIN RESULTS: The
      concentrations of ex vivo tumor necrosis factor (TNF)-alpha, IL-6, IL-8, and IL
      10, measured by enzyme-linked immunosorbent assay, were reduced in both
      experimental settings. In patients on CPB, LPS hyporesponsiveness was detected at
      60 mins after the onset of CPB and was maximal at 120 mins (78% to 86% decreases
      from pre-CPB levels) but was transient, except for TNF-alpha. The plasma
      concentration of IL-10 peaked at 90 mins after the start of CPB, but the role of
      IL-10 in LPS hyporesponsiveness appears limited because anti-IL-10 antibodies
      significantly increased ex vivo production of IL-6 but not TNF-alpha or IL-8. In
      the isolated ECC study, no IL-10 was detected in plasma, yet the ex vivo
      production of the cytokines (except IL-8) was decreased (by 66% to 95%).
      CONCLUSION: Our results demonstrate the following: a) CPB induces an early and
      transient LPS hyporesponsiveness of whole blood as measured by cytokine
      production; b) IL-10 seems only partly involved in this process, and its role is
      restricted to an in vivo situation; and c) contact of blood with an ECC is
      sufficient to induce LPS hyporesponsiveness.

PMID- 10890610
TI  - Systemic hemodynamics, gastric intramucosal PCO2 changes, and outcome in
      critically ill burn patients.
AB  - OBJECTIVES: To define the hemodynamic and gastric intramucosal PCO2 (PiCO2)
      changes during the first 48 hrs after burn trauma and to analyze their
      relationship with outcome. DESIGN: Prospective, observational study in a cohort
      of consecutively admitted critically ill burn patients. SETTING: Intensive care
      burn unit in a university hospital. PATIENTS: Forty-two patients with burns
      covering >20% of body surface area or inhalation injury. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Patients were monitored with an oximetric
      pulmonary arterial catheter and a gastric tonometer to measure PiCO2. The
      difference between arterial and gastric mucosal PCO2 (P[i-a]CO2) was considered
      indicative of gastric mucosal hypoxia. Hemodynamic and PiCO2 measurements were
      performed during the first 48 hrs after admission. Patients suffered burns
      covering 36.1% +/- 14.3% (mean +/- SD) and 45.3% +/- 21.9% of body surface area
      (survivors and nonsurvivors, respectively). All patients were successfully
      resuscitated by conventional standards. Nonsurvivors (n = 16) died a median of 17
      days after admission. In univariate analysis, the presence of shock during the
      resuscitation phase, age, mixed venous pH, P[i-a]CO2, right atrial pressure,
      pulmonary arterial pressure, pulmonary arterial occlusion pressure, cardiac
      index, systemic and pulmonary vascular resistance, left ventricular stroke work
      index, mixed venous oxygen saturation, and systemic oxygen delivery, consumption,
      and extraction ratio, measured over the first 12 hrs after admission, were
      significantly (p < .05) different between survivors and nonsurvivors. These
      differences disappeared after 12 hrs after admission. Multivariate analysis
      identified age, percentage body surface area burned, and oxygen delivery index (6
      hrs after admission) as factors independently associated with a poor outcome. P[i
      a]CO2 (12 hrs after admission) was significantly greater in patients with than in
      those without inhalation injury (17 +/- 13 torr [2.26 +/- 1.73 kPa] vs. 6 +/- 10
      torr [0.79 +/- 1.33 kPa]; p = .005). Patients with a P[i-a]CO2 difference (6 hrs
      after admission) > or =10 torr (1.33 kPa) had a mortality rate of 56% vs. 25% of
      those patients with <10 torr (p = .044). CONCLUSIONS: Our data indicate that
      there are hemodynamic and biochemical changes that occur early after burn trauma
      that are associated with prognosis after an apparently successful resuscitation.
      Particularly, a hemodynamic profile characterized by systemic acidosis, low
      systemic blood flow, and systemic and pulmonary vasoconstriction early after
      trauma is associated with a poor outcome. Additionally, intestinal mucosal
      acidosis occurs after burn trauma, is influenced by inhalation injury, and is a
      variable related to outcome.

PMID- 10890611
TI  - Effect of inhaled nitric oxide on key mediators of the inflammatory response in
      patients with acute lung injury.
AB  - OBJECTIVE: Inhaled nitric oxide is used to treat hypoxia associated with acute
      lung injury. Endogenous nitric oxide regulates inflammatory responses, but the
      effect of inhaled nitric oxide therapy is unknown. We hypothesized that inhaled
      nitric oxide may alter inflammatory responses and endogenous nitric oxide
      synthase activity. DESIGN: A randomized, prospective interventional study.
      SETTING: A university hospital's general intensive care unit. PATIENTS: Thirty
      two patients with acute lung injury. INTERVENTIONS: Patients who responded to
      test doses of nitric oxide were randomized to ventilator therapy with and without
      inhaled nitric oxide. The inhaled concentration of nitric oxide was determined by
      dose titration at 0, 2, 10, and 40 ppm and the minimum concentration used, which
      resulted in an increase in the PaO2/FIO2 ratio of at least 25%. MEASUREMENTS AND
      MAIN RESULTS: Patients were followed up for 30 days or until death, and
      bronchoalveolar lavage (BAL) was performed at 0, 24, and 72 hrs. Nitric oxide
      synthase activity was measured spectrophotometrically, and myeloperoxidase,
      elastase, interleukin-8, and leukotrienes were measured in BAL fluid by enzyme
      immunoassay. Total nitrite and lipid peroxides in serum were measured
      colorimetrically. Nitric oxide synthase activity decreased (p = .01) and total
      nitrite increased (p = .02) in patients receiving inhaled nitric oxide. Other
      markers of inflammation in BAL fluid did not change. Lipid peroxide
      concentrations also did not alter. CONCLUSIONS: The decrease in activity of
      nitric oxide synthase in patients receiving nitric oxide is likely to be the
      result of feedback inhibition of the enzyme. This study shows that inhaled nitric
      oxide has no effect on several markers of the inflammatory response system and
      does not lead to increased oxidant stress.

PMID- 10890612
TI  - The incidence of ventilator-associated pneumonia and success in nutrient delivery
      with gastric versus small intestinal feeding: a randomized clinical trial.
AB  - BACKGROUND: Enteral feeding provides nutrients for patients who require
      endotracheal tubes and mechanical ventilation. There is a presumed increase in
      the risk of ventilator-associated pneumonia (VAP) with tube feeding. This has
      stimulated the development of procedures for duodenal intubation and small
      intestinal (SI) feeding as primary prophylaxes to prevent VAP. OBJECTIVE: To
      investigate the rate of VAP and adequacy of nutrient delivery with gastric (G)
      vs. SI feeding. DESIGN: A prospective, randomized, controlled trial. SETTING: A
      medical intensive care unit of a county hospital. PATIENTS: A total of 44
      endotracheally intubated, mechanically ventilated patients requiring enteral
      nutrition. INTERVENTION: Subjects were randomized to receive enteral nutrition
      via G or SI feeding. Protocols directed the placement of the feeding tube and the
      infusion of enteral nutrition and defined the radiographic and clinical criteria
      for a diagnosis of VAP. MEASUREMENTS AND OUTCOMES: The incidence of VAP and the
      adequacy of nutritional supplementation were prospectively followed. The relative
      risk of VAP with SI was 1.1 (95% confidence interval 0.96-2.44) compared with G.
      The SI group received a greater percentage of their caloric requirements (SI 69
      +/- 7% vs. G 47 +/- 7%, mean +/- SEM, p < .05). Mortality did not differ between
      G (26 +/- 9%) and SI (24 +/- 10, p = .86). CONCLUSIONS: There is no clear
      difference in the incidence of VAP in SI compared with G enteral nutrition.
      Patients given feeding into the SI do receive higher calorie and protein intakes.

PMID- 10890613
TI  - Incidence and clinical pattern of the abdominal compartment syndrome after
      "damage-control" laparotomy in 311 patients with severe abdominal and/or pelvic
      trauma.
AB  - OBJECTIVE: To investigate the incidence, main physiologic effects, and
      therapeutic management of the abdominal compartment syndrome (ACS) after severe
      abdominal and/or pelvic trauma. DESIGN: Retrospective analysis from January 1991
      to December 1996; prospective study from January 1997 to August 1998. SETTING:
      Level I trauma center, intensive care unit. PATIENTS: A total of 311 patients
      with severe abdominal and/or pelvic trauma and "damage-control" laparotomy on day
      of admission. INTERVENTIONS: The ACS was defined as the development of
      significant respiratory compromise, including elevated inspiratory pressure of
      >35 mbar, a decreased Horowitz quotient (<150 torr [<20 kPa]), renal dysfunction
      (urine output, <30 mL/hr), hemodynamic instability necessitating catecholamines,
      and a rigid or tense abdomen. Beginning with January 1997, urinary bladder
      pressure as an additional variable for the diagnosis of ACS was continuously
      measured in patients (n = 12) at risk. Bladder pressures of >25 mm Hg indicated
      ACS. MEASUREMENTS AND MAIN RESULTS: Seventeen patients (5.5%) developed ACS
      because of persistent intra-abdominal/retroperitoneal bleeding (n = 12; 70.6%) or
      visceral edema (n = 5; 29.4%). All patients with ACS underwent primary fascial
      closure. In eight of these patients (47%), abdominal and/or pelvic packing for
      hemostasis was performed. All patients with ACS required decompressive emergency
      laparotomies because of physiologic derangements. The time between primary
      laparotomy and decompressive laparotomy was 12.9 +/- 2.0 hrs. Emergency
      decompression of the abdomen resulted in a significant increase in the cardiac
      index (+146%), tidal volume (+133%), Horowitz quotient (+156%), and urine output
      (+1557%), whereas bladder pressure (-63%), heart rate (-19%), central venous
      pressure (-30%), pulmonary artery occlusion pressure (-43%), peak airway pressure
      (-31%), partial pressure arterial carbon dioxide (-30%), and lactate (-40%)
      markedly (p < .05) decreased. In two multiply injured patients with additional
      head trauma, ACS caused a critical increase of the intracranial pressure, which
      markedly dropped after the release of abdominal tension. CONCLUSIONS: Risk
      factors for the occurrence of ACS are severe abdominal and/or pelvic trauma,
      which require laparotomy and packing for the control of hemorrhage. The ACS
      occurs within hours and causes life-threatening physiologic derangements and a
      critical rise in intracranial pressure in patients with combined abdominal/pelvic
      and head trauma. Decompressive laparotomy immediately restores impaired organ
      functions. In patients at risk, the continuous measurement of urinary bladder
      pressure as a simple, noninvasive, and less expensive diagnostic tool for early
      detection of elevated intra-abdominal pressure is mandatory.

PMID- 10890614
TI  - Surgery and intensive care procedures affect the target site distribution of
      piperacillin.
AB  - OBJECTIVE: Therapeutic failure of antibiotic therapy has been ascribed to
      pharmacokinetic alterations in compromised patient populations. The present
      study, therefore, aimed at examining the influences of cardiac surgery and
      intensive care procedures on the postoperative target site distribution of
      piperacillin. For this purpose, the penetration of piperacillin to the
      interstitial space fluid, the relevant target site for most bacterial infections,
      was compared between patients after aortic valve replacement and healthy
      volunteers. DESIGN: Comparative study in two study populations. SETTING: The
      intensive care unit and research ward of a university hospital. PATIENTS: The
      study population included six otherwise healthy patients scheduled to undergo
      aortic valve replacement and a control group of six healthy male volunteers.
      INTERVENTIONS: After the administration of a single i.v. infusion of 4.0 g
      piperacillin, free piperacillin concentrations were measured in the interstitium
      of skeletal muscle and subcutaneous tissue by in vivo microdialysis and in venous
      serum. Piperacillin concentrations were assayed with reversed phase high
      performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: Interstitial
      piperacillin concentrations in muscle and subcutaneous adipose tissue were
      significantly lower in patients compared with volunteers with the area under the
      curve for the interstitium/area under the curve for serum concentration ratios
      ranging from 0.25 to 0.27 and from 0.43 to 1.22 in patients and volunteers,
      respectively (p < .05 between groups). The terminal elimination half-life was
      markedly prolonged in patients, leading to a concomitant increase in t > minimal
      inhibitory concentration (MIC) values, the relevant surrogate for therapeutic
      success of therapy with beta-lactam antibiotics, for strains with MIC50 <4
      microg/mL. For strains with MIC50 >20 microl/mL, however, inadequate target site
      concentrations were attained in the patient population. CONCLUSIONS: During the
      postoperative and intensive care periods, target site concentrations of
      piperacillin are markedly altered and decreased. This may also be true for other
      antibiotic agents and may have clinical implications in that current dosing
      guidelines may result in inadequate target site concentrations for high-MIC
      strains. Conceivably, this could lead to therapeutic failure in some patients.

PMID- 10890615
TI  - Effects of positive end-expiratory pressure on hemodynamics and indocyanine green
      kinetics in patients after orthotopic liver transplantation.
AB  - OBJECTIVE: To determine the impact of positive end-expiratory pressure (PEEP)
      ventilation on hemodynamics and a clinical test for assessment of dynamic liver
      performance in patients undergoing orthotopic liver transplantation (OLT).
      DESIGN: Prospective, descriptive patient study. SETTING: University hospital
      intensive care unit. PATIENTS: A total of 25 patients after OLT. INTERVENTIONS:
      All patients were intubated and mechanically ventilated with biphasic positive
      airway pressure. The effects of three different randomly chosen levels of PEEP (0
      cm H2O, 5 cm H2O, and 10 cm H2O) were studied in the immediate postoperative
      period. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, arterial and venous
      blood gas analyses, and plasma disappearance rate of indocyanine green
      (ICG(PDR)), using the transpulmonary indicator dilution technique, were obtained
      simultaneously. For data evaluation, patients were grouped retrospectively
      according to their hemodynamic response to PEEP (Group A and Group B). In Group A
      (n = 13), PEEP did not alter cardiac index. In Group B (n = 11), PEEP levels of 5
      cm H2O and 10 cm H2O significantly reduced cardiac index and oxygen delivery.
      ICG(PDR) remained statistically unchanged in both groups. CONCLUSIONS: Short-term
      pressure-controlled ventilation with PEEP levels of up to 10 cm H2O does not
      exert detrimental effects on systemic hemodynamics in OLT patients and does not
      interfere with ICG(PDR). However, it remains to be determined whether these
      findings could be confirmed under the application of higher PEEP levels over a
      longer period of time and whether they could be of clinical relevance for the use
      of indocyanine green as a dynamic liver function test.

PMID- 10890616
TI  - Factors influencing changes in surgical intensive care unit utilization.
AB  - OBJECTIVES: To determine the factors that cause changes in surgical intensive
      care unit (ICU) utilization. The aim was to uncover the causes of these changes
      and examine whether any could have been predicted statistically. DESIGN:
      Retrospective analysis of prospectively collected representative data. SETTING:
      University hospital adult surgical ICU. PATIENTS: A total of 6,571 consecutive
      patients admitted over 8 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Changes in annual admission rates and lengths of stay were examined to determine
      their causes, whether they were because of structural changes caused by
      alterations of physical facilities, functional changes caused by changes in
      personnel or policies, or clinical changes caused by alterations in clinical
      practice. The medical literature was examined to determine whether these changes
      reflected medical trends. During the 8 yrs there was a steady increase in the
      number of admissions and a steady reduction in the length of stay. These changes
      in unit utilization were often not predictable statistically and were
      attributable to a combination of clinical, structural, and functional factors.
      CONCLUSIONS: Surgical ICU utilization was notable for continual, and not
      predictable, changes. Clinical issues included new surgical techniques and
      anesthetic practices; structural causes included changes in bed capacity and
      opening an intermediate care unit; and functional factors involved changes in
      surgical personnel, policy revisions, and pressures to reduce ICU length of stay.
      This was further complicated by the observation that changes in the number of
      admissions were often not paralleled by similar changes in the number of patient
      days. This complex situation demonstrated the problems of basing predictions of
      future utilization on previous experiences.

PMID- 10890617
TI  - Ornithine alpha-ketoglutarate improves wound healing in severe burn patients: a
      prospective randomized double-blind trial versus isonitrogenous controls.
AB  - OBJECTIVE: To compare the effectiveness on wound healing time in severe burn
      patients of ornithine alpha-ketoglutarate supplementation of enteral feeding vs.
      an isonitrogenous control. Previous clinical and experimental studies suggest a
      beneficial effect of enterally administered ornithine alpha-ketoglutarate
      supplementation on protein metabolism in burn patients, but few data deal with
      clinical outcome. DESIGN: Prospective double-blind randomized trial. SETTING:
      Burn treatment center of an army hospital. PATIENTS: Forty-seven severe burn
      patients with total burned body surface areas of 25% to 95% and presence of full
      thickness burn who were prescribed early exclusive enteral nutrition. Either
      ornithine alpha-ketoglutarate or isonitrogenous control (soy protein mixture,
      Protil-1) were administered twice a day as a bolus (2 x 10 g) at 9 am and 9 pm
      for 3 wks. The patients were evaluated for wound healing time (primary end
      point), antibiotic use, tolerance, duration of enteral nutrition, and nutritional
      status. INTERVENTIONS: Serial blood samples were collected in each patient for
      determination of serum transthyretin and plasma phenylalanine, and urine sampling
      was performed for determination of 3-methylhistidine excretion at day 4 and day
      21 after burn injury. MEASUREMENTS AND MAIN RESULTS: Wound healing times in
      patients receiving ornithine alpha-ketoglutarate or Protil-1 were 60 +/- 7 and 90
      +/- 12 days, respectively (p < .05) for similar grafted surfaces. Based on
      increased serum transthyretin concentrations, both groups showed an improvement
      of nutritional status at day 21 after burn. Taking a cut-off value of 110 unit
      burn standard for severity of injury, plasma phenylalanine concentrations, and
      urinary 3-methylhistidine/creatinine ratio were significantly reduced (p < .05)
      in the less severe burn patients (<110 unit burn standard) supplemented with
      ornithine alpha-ketoglutarate. CONCLUSIONS: Ornithine alpha-ketoglutarate
      supplementation of enteral feeding significantly shortens wound healing time in
      severe burn patients. In addition, ornithine alpha-ketoglutarate administration
      was safe and well tolerated and decreased protein hypercatabolism in the less
      severe burn patients.

PMID- 10890618
TI  - Screening tests of disseminated intravascular coagulation: guidelines for rapid
      and specific laboratory diagnosis.
AB  - OBJECTIVE: To study the clinician's ordering pattern in the diagnosis of
      disseminated intravascular coagulation (DIC) and to analyze the utility of
      selected tests by assessing their sensitivity, specificity, and overall
      efficiency. DESIGN: Retrospective, nonrandomized, clinical study. SETTING:
      University hospital intensive care units. PATIENTS: A total of 82 inpatients
      treated in our intensive care units were identified from the hospital computer
      system as having been tested for DIC in a 3-month period. INTERVENTION: Screening
      tests for DIC were ordered for the suspected patients. MEASUREMENTS AND MAIN
      RESULTS: Prothrombin time (PT), partial thromboplastin time (PTT),
      fibrinogen/fibrin degradation products (FDP), and fibrinogen were used most
      frequently as DIC diagnostic tests. The FDP and D-dimer combination (n = 39) had
      the highest diagnostic efficiency of 95%, with sensitivity being 91% and
      specificity 94%. This is followed by FDP (n = 71), efficiency 87%, sensitivity
      100%, and specificity 67%; PT/PTT and FDP combination (n = 71), efficiency 86%,
      sensitivity 91%, and specificity 71%; and D-dimer (n = 44), efficiency 80%,
      sensitivity 91%, and specificity 68%. The rest of the commonly used tests, such
      as PT, PTT, thrombin time, platelet count, fibrinogen, and the presence of
      schistocytes (n = 80), had individually either low specificity or low sensitivity
      and, therefore, low efficiency scores (57%, 57%, 70%, 67%, 65%, and 51%,
      respectively). CONCLUSIONS: The D-dimer and FDP tests offered the best test panel
      in the diagnosis of DIC. We propose the use of D-dimer, FDP, and antithrombin as
      the DIC diagnostic test panel, with D-dimer and FDP providing a rapid and
      specific diagnosis, antithrombin providing insight to the severity and prognosis,
      and FDP (rapid and less expensive than D-dimer) to follow-up the progress of the
      condition once the diagnosis is established.

PMID- 10890619
TI  - Refractory delirium tremens treated with propofol: a case series.
AB  - Delirium tremens, the most serious manifestation of alcohol withdrawal, occurs in
      approximately 5% of hospitalized alcoholics and has a mortality rate approaching
      15%. Patients with delirium tremens are usually treated in an intensive care unit
      in which benzodiazepines form the cornerstone of therapy. In this report, we
      describe four patients who proved refractory to high doses of benzodiazepines and
      were successfully treated with a propofol infusion.

PMID- 10890620
TI  - Physiologic evaluation of noninvasive mechanical ventilation delivered with three
      types of masks in patients with chronic hypercapnic respiratory failure.
AB  - OBJECTIVE: The efficacy of noninvasive mechanical ventilation (NIMV) in improving
      breathing pattern and arterial blood gases (ABG) in hypercapnic patients has been
      well documented; however, little attention has been given to the choice of the
      interface and the ventilatory mode. We evaluated the effects of three types of
      masks and two modes of ventilation on patients' ABG, breathing pattern, and
      tolerance to ventilation. DESIGN: Prospective randomized study. SETTING: Two
      respiratory weaning centers. PATIENTS: A total of 26 stable hypercapnic patients
      (pH, 7.38 +/- 0.04; PaCO2, 59.2. +/- 10.9 torr) had not received NIMV and were
      affected by restrictive thoracic disease or obstructive pulmonary disease.
      INTERVENTIONS: Three 30-min runs of NIMV, delivered using volume-assisted (n =
      13) or pressure-assisted modes of partial mechanical support (n = 13), were
      performed in random order with a full-face mask, a nasal mask, and nasal plugs.
      MEASUREMENTS: ABG, breathing pattern, and patients' tolerance to ventilation.
      MAIN RESULTS: Compared with spontaneous breathing, the application of NIMV
      significantly improved ABG and minute ventilation, irrespective of the
      ventilatory mode, the underlying pathology or the type of mask. Overall, a nasal
      mask was better tolerated than the other two interfaces (p < .005 vs. nasal plugs
      and full-face mask). PaCO2 was significantly lower (p < .01) with a full-face
      mask or nasal plugs than with a nasal mask (49.5 +/- 9.4 torr, 49.7 +/- 8 torr,
      and 52.4 +/- 11 torr, respectively). Minute ventilation was significantly higher
      with a full-face mask than with a nasal mask because of an increase in tidal
      volume. No differences were observed in tolerance to ventilation, ABG, or
      breathing pattern, using assist control or pressure-assisted modes. CONCLUSIONS:
      In this physiologic study, we have shown that in patients with hypercapnic
      respiratory failure, irrespective of the underlying pathology, the type of
      interface affects the NIMV outcome more than the ventilatory mode.

PMID- 10890621
TI  - Physiologic effects of early administered mask proportional assist ventilation in
      patients with chronic obstructive pulmonary disease and acute respiratory
      failure.
AB  - OBJECTIVE: To evaluate the physiologic short-term effects of noninvasive
      proportional assist ventilation (PAV) in patients with acute exacerbation of
      chronic obstructive pulmonary disease (COPD). DESIGN: Prospective, physiologic
      study. SETTING: Respiratory intermediate intensive care unit. PATIENTS: Seven
      patients with acute respiratory failure requiring noninvasive mechanical
      ventilation because of exacerbation of COPD. INTERVENTIONS: PAV was administered
      by nasal mask as first ventilatory intervention. The setting of PAV involved a
      procedure to adjust volume assist and flow assist to levels corresponding to
      patient comfort. Volume assist was also set by means of the "run-away" procedure.
      Continuous positive airway pressure (CPAP) amounting to 2 cm H2O was always set
      by the ventilator. This setting of assistance (PAV) was applied for 45 mins.
      Thereafter, CPAP was increased to 5 cm H2O (PAV + CPAP-5) without any change in
      the PAV setting and was administered for 20 mins. Oxygen was delivered through a
      port of the mask in the attempt to maintain a target SaO2 >90%. MEASUREMENTS AND
      MAIN RESULTS: Arterial blood gases, breathing pattern, and inspiratory effort
      were measured during unsupported breathing and at the end of PAV, and breathing
      pattern and inspiratory effort were measured after 20 mins of PAV + CPAP-5. PAV
      determined a significant increase in tidal volume and minute ventilation (+64%
      and +25% on average, respectively) with unchanged breathing frequency and a
      significant improvement in arterial blood gases (PaO2 with the same oxygen
      supply, from 65 +/- 15 torr to 97 +/- 36 torr; PaCO2, from 80 +/- 11 torr to 76
      +/- 13 torr; pH, from 7.30 +/- 0.02 to 7.32 +/- 0.03). The pressure-time product
      calculated over a period of 1 min (from 318 +/- 87 to 205 +/- 145 cm H2O x sec x
      min(-1)) was significantly reduced. PAV + CPAP-5 resulted in a further although
      not significant decrease in the pressure-time product calculated over a period of
      1 min (to 183 +/- 110 cm H2O x sec x min(-1)), without additional changes in the
      breathing pattern. CONCLUSIONS: Noninvasive PAV is able to improve arterial blood
      gases while unloading inspiratory muscles in patients with acute exacerbation of
      COPD.

PMID- 10890622
TI  - Simultaneous comparison of thoracic bioimpedance and arterial pulse waveform
      derived cardiac output with thermodilution measurement.
AB  - OBJECTIVE: To compare the accuracy and reliability of thoracic electrical
      bioimpedance (TEB) and the arterial pulse waveform analysis with simultaneous
      measurement of thermodilution cardiac output (TD-CO) in critically ill patients.
      DESIGN: Prospective data collection. SETTING: Emergency department and critical
      care unit in a 2,000-bed inner-city hospital. PATIENTS: A total of 29 critically
      ill patients requiring invasive hemodynamic monitoring for clinical management
      were prospectively studied. INTERVENTIONS: Noninvasive cardiac output was
      simultaneously measured by a TEB device and by analysis of the arterial pulse
      waveform derived from the finger artery. Invasive cardiac output was determined
      by the thermodilution technique. MEASUREMENTS AND MAIN RESULTS: A total of 175
      corresponding TD-CO and noninvasive hemodynamic measurements were collected in 30
      min intervals. They revealed an overall bias of 0.34 L/min/m2 (95% confidence
      interval, 0.24-0.44 L/min/m2; p < .001) for the arterial pulse waveform analysis
      and of 0.61 L/min/m2 (95% confidence interval, 0.50-0.72 L/min/m2; p < .001) for
      the TEB. In 39.4% (n = 69) of all measurements, the discrepancy between arterial
      pulse waveform analysis and TD-CO was >0.50 L/min/m2. The discrepancies of the
      arterial pulse waveform analysis correlated positively with the magnitude of the
      cardiac index (r2 = 0.29; p < .001). In 56.6% (n = 99) of all measurements, the
      discrepancy between TEB and TD-CO was >0.50 L/min/m2. The magnitude of the
      discrepancies of the TEB was significantly correlated with age (r2 = 0.17; p =
      .02). Measurements were in phase in 93.2% of all arterial pulse waveform analysis
      and in 84.9% of all TEB readings (p < .001). CONCLUSIONS: The arterial pulse
      waveform analysis exhibits a greater accuracy and reliability as compared with
      the TEB with regard to overall bias, number of inaccurate readings, and phase
      lags. The arterial pulse waveform analysis may be useful for the monitoring of
      hemodynamic changes. However, both methods fail to be a substitute for the TD-CO
      because of a substantial percentage of inaccurate readings.

PMID- 10890623
TI  - Pyroglutamic acidemia: a cause of high anion gap metabolic acidosis.
AB  - OBJECTIVE: To report four cases of pyroglutamic acidemia in adults causing
      clinically significant acidosis. DATA SOURCES: Patients admitted to the intensive
      care units of the Alfred Hospital (a quaternary referral center) and Geelong
      Hospital (a major regional center) with an unexplained high anion gap acidosis.
      CONCLUSIONS: Pyroglutamic acidemia (5-oxoprolinemia) is a rare cause of high
      anion gap metabolic acidosis that should be suspected in patients presenting with
      sepsis, hepatic, and/or renal dysfunction who are receiving drugs such as
      acetaminophen, flucloxacillin, and vigabatrin after the more common causes of a
      high anion gap acidosis have been excluded. Should pyroglutamic aciduria be
      present, known precipitants should be ceased, infection should be managed
      aggressively, and supportive management should be instituted.

PMID- 10890624
TI  - Early natural course of transient encephalopathy after coronary artery bypass
      grafting.
AB  - OBJECTIVE: A decline of neuropsychological performance is an unwanted side effect
      of coronary artery bypass grafting (CABG) with extracorporeal circulation. There
      is little data on the neuropsychological changes during the first 2 wks after
      CABG. DESIGN, SETTING, PATIENTS: In this prospective observational study at our
      university medical center, a group of 67 patients who underwent routine CABG was
      selected for absence of comorbidity (such as carotid stenosis, previous stroke,
      dementia, and advanced general medical disorders) and examined. In this selected
      group of patients, no focal deficit was seen throughout the study. A total of 20
      hospitalized patients with different types of peripheral neuropathy and free from
      drugs interfering with cognition served as a control group for the practice
      effects of the neuropsychological testing. MEASUREMENTS AND MAIN RESULTS: Seven
      standard tests covering different neuropsychological domains were used as a
      composite battery. Examinations took place before surgery and serially at days 3,
      6, and 9 after CABG; general neurologic examination was done every day, including
      the first postoperative day. We observed a definite decline in all tests at day 3
      (p < .01) and progressive recovery thereafter up to or even beyond preoperative
      values within 9 days (p < .01). Transient depression as indicated by self-rated
      scores occurred in some patients. CONCLUSION: We observed a uniform, but
      transient, deterioration in performance on a battery of frequently repeated
      standardized neuropsychological tests early after CABG. Our data on the early
      natural course may help to better evaluate treatment efforts aimed at preventing
      or reducing after-surgery neuropsychological alterations.

PMID- 10890625
TI  - Plasma redox status relates to severity in critically ill patients.
AB  - OBJECTIVE: To determine the relation between plasma redox status and severity of
      illness for patients admitted to an intensive care unit (ICU). DESIGN: A
      prospective cohort study. SETTING: A mixed medical and surgical adult ICU with 12
      beds. PATIENTS: A total of 73 consecutive patients admitted to the ICU.
      INTERVENTIONS: Venous blood samples were routinely obtained within 24 hrs of
      admission. MEASUREMENTS AND MAIN RESULTS: Plasma total antioxidant capacity and
      lipoperoxides were measured by spectrophotometric technique at admission to the
      ICU. The plasma ratio total antioxidant capacity (mM)/lipoperoxides (microM) was
      used as an index of plasma redox status. Plasma concentration of the markers of
      leukocyte activation myeloperoxidase (enzyme-linked immunosorbent assay) and
      polymorphonuclear-elastase (immunoactivation assay) were also measured at
      admission to the ICU. Analysis of correlation between plasma ratio total
      antioxidant capacity/lipoperoxides and APACHE III score showed a negative
      association (p < .001, Spearman correlation test). Myeloperoxidase and
      polymorphonuclear-elastase correlated positively with Acute Physiology and
      Chronic Health Evaluation III scores (r2 = 0.58; p < .001; and r2 = 0.05; p =
      .035; respectively). CONCLUSIONS: Plasma redox status relates to severity in
      critically ill patients. We propose that it would be reasonable to provide
      antioxidant therapy as part of routine management of patients admitted to a mixed
      ICU, regardless of the specific reason for ICU admission. Plasma redox status
      might become useful to evaluate the risk in critically ill patients.

PMID- 10890626
TI  - Endotracheal versus intravenous epinephrine and atropine in out-of-hospital
      "primary" and postcountershock asystole.
AB  - STUDY OBJECTIVE: Pulmonary blood flow during cardiac arrest and cardiopulmonary
      resuscitation (CPR) is <20% of normal, and transalveolar drug absorption is
      likely to be minimal. Animal and clinical CPR studies have not addressed the use
      of endotracheal (ET) epinephrine in doses currently recommended for adults (twice
      the intravenous dose). The purpose of this study was to compare the effects of ET
      and intravenous drugs on cardiac rhythm in the prehospital setting. DESIGN: A 3
      yr (1995-1997) retrospective review of all cardiac arrests transported to a
      single, municipal teaching institution was performed. PATIENTS: Patients >18 yrs
      in atraumatic cardiac arrest whose first documented field rhythm was asystole
      with time-to-definitive care of < or =10 mins (primary asystole) and patients
      found in ventricular fibrillation who developed postcountershock asystole
      (secondary asystole) were included. Patients were grouped according to route of
      drug administration (i.v., ET, or no drug therapy) as well as rhythm (primary or
      secondary asystole). A positive response to drug therapy was defined as any
      subsequent rhythm other than asystole during continued prehospital resuscitation.
      MEASUREMENTS AND MAIN RESULTS: A total of 136 patients met inclusion criteria.
      The following groups were defined: group 1, primary asystole/i.v. drugs (n = 39);
      group 2, postcountershock asystole/i.v. drugs (n = 39); group 3, primary
      asystole/ET drugs (n = 25); group 4, postcountershock asystole/ET drugs (n = 18);
      and group 5, primary or secondary asystole/no drug therapy (n = 15). Significant
      differences were not observed between groups with respect to age, gender,
      witnessed arrest, frequency of bystander CPR, or time-to-definitive care. The
      positive rhythm response rate was significantly greater in group 1 (64%) and
      group 2 (69%) (both p < .01) than in Group 3 (12%) or group 4 (11%). The response
      rate in the control group was 20% and not significantly different from either ET
      group. The intravenous groups also had a significantly greater rate of return of
      spontaneous circulation (17%) when compared with the ET groups (0%) (p = .005).
      CONCLUSION: We conclude that the currently recommended doses of epinephrine and
      atropine administered endotracheally are rarely effective in the setting of
      cardiac arrest and CPR.

PMID- 10890627
TI  - Assessment of the performance of five intensive care scoring models within a
      large Scottish database.
AB  - OBJECTIVE: To assess and compare the performance of five severity of illness
      scoring systems used commonly for intensive care unit (ICU) patients in the
      United Kingdom. The five models analyzed were versions II and III of the Acute
      Physiology and Chronic Health Evaluation (APACHE) system, a version of APACHE II
      using United Kingdom (UK)-derived coefficients (UK APACHE II), version II of the
      Simplified Acute Physiology Score (SAPS), and version II of the Mortality
      Probability Model, computed at admission (MPM0) and after 24 hrs in the ICU
      (MPM24). DESIGN: A 2-yr prospective cohort study of consecutive admissions to
      intensive care units. SETTING: A total of 22 general ICUs in Scotland PATIENTS: A
      total of 13,291 admissions to the study, which after prospectively agreed
      exclusions left a total of 10,393 patients for the analysis. OUTCOME MEASURES:
      Death or survival at hospital discharge. MEASUREMENTS AND MAIN RESULTS: All the
      models showed reasonable discrimination using the area under the receiver
      operating characteristic curve (APACHE III, 0.845; APACHE II, 0.805; UKAPACHE II,
      0.809; SAPS II, 0.843; MPM0, 0.785; MPM24, 0.799). The levels of observed
      mortality were significantly different than that predicted by all models, using
      the Hosmer-Lemeshow goodness-of-fit C test (p < .001), with the results of the
      test being confirmed by calibration curves. When excluding patients discharged in
      the first 24 hrs to allow for comparisons using the same patient group, APACHE
      III, MPM24, and SAPS II (APACHE III, 0.795; MPM24, 0.791; SAPS II, 0.784) showed
      significantly better discrimination than APACHE II, UK APACHE II, and MPM0
      (APACHE II, 0.763; UK APACHE II, 0.756; MPM0, 0.741). However, calibration
      changed little for all models with observed mortality still significantly
      different from that predicted by the scoring systems (p < .001). For equivalent
      data sets, APACHE II demonstrated superior calibration to all the models using
      the chi-squared value from the Hosmer-Lemeshow test for both populations (APACHE
      III, 366; APACHE II, 67; UKAPACHE II, 237; SAPS II, 142; MPM0, 452; MPM24, 101).
      CONCLUSIONS: SAPS II demonstrated the best overall performance, but the superior
      calibration of APACHE II makes it the most appropriate model for comparisons of
      mortality rates in different ICUs. The significance of the Hosmer-Lemeshow C test
      in all the models suggest that new logistic regression coefficients should be
      generated and the systems retested before they could be used with confidence in
      Scottish ICUs.

PMID- 10890628
TI  - Serum procalcitonin levels in bacterial and abacterial meningitis.
AB  - OBJECTIVES: To test the hypothesis that serum procalcitonin (PCT) levels are
      elevated in patients with bacterial meningitis and remain within normal limits in
      patients with abacterial meningitis. DESIGN: Prospective case series. SETTING:
      Tertiary care center. PATIENTS: A total of 30 patients (13 men and 17 women) with
      a mean age of 52 yrs, having acute bacterial (n = 16) or abacterial (n = 14)
      meningitis. INTERVENTIONS: Blood and cerebrospinal fluid samples. MEASUREMENTS
      AND MAIN RESULTS: Patients with abacterial meningitis were younger and had a
      shorter hospital stay. Of 16 patients with bacterial meningitis, 14 were in a
      septic condition at admission, but only 5 of 14 patients with abacterial
      meningitis were in a septic condition at admission. At discharge, 12 patients
      were without symptoms, 9 patients were moderately disabled, and 9 were severely
      disabled. No patient died. At admission, PCT, C-reactive protein, white blood
      cell and cerebrospinal fluid leukocyte counts, and cerebrospinal fluid protein
      and lactate levels were higher and the serum/cerebrospinal fluid glucose quotient
      was lower in patients with bacterial meningitis as compared with those with
      abacterial meningitis (p < .001). PCT was the variable with the highest
      specificity for bacterial infections (100%), but there were false-negative
      findings in five patients with bacterial meningitis (a sensitivity of 69%).
      Persistently elevated or increasing PCT levels after 2 days were associated with
      an unfavorable clinical course. CONCLUSIONS: Our results indicate that PCT is a
      useful additional variable for distinguishing bacterial from abacterial
      meningitis. In patients with abacterial meningitis, PCT levels do not increase
      even in cases of viral sepsis. Elevated PCT levels indicate a bacterial origin
      with high specificity, but false-negative results can occur.

PMID- 10890629
TI  - The pathophysiologic and prognostic significance of acidosis in severe adult
      malaria.
AB  - OBJECTIVE: To investigate the pathophysiology and prognostic significance of
      acidosis in severe adult malaria. DESIGN: Cohort study. SETTING: The intensive
      care unit of an infectious diseases hospital in southern Vietnam. PATIENTS: Three
      hundred forty-six consecutive adult patients with severe falciparum malaria.
      INTERVENTIONS: Measurements of baseline venous lactate and pyruvate
      concentrations and an extensive range of clinical and laboratory variables were
      made, and patients were followed up carefully until death or discharge from the
      hospital. Admission arterial blood pH and gas tensions were recorded in 296
      patients, and hepatic venous sampling was done in 12 patients. MEASUREMENTS AND
      MAIN RESULTS: Overall, 198 (67%) patients were acidotic (standard base deficit
      [SBD], >3.3 mmol/L [n = 196], or arterial Pco2, >45 torr [6 kPa] [n = 3]).
      Hyperlactatemia (plasma lactate, >4 mmol/L) occurred in 120 (35%) of the 346
      patients and was associated significantly with acidosis (p < .0001). The
      hepatosplanchnic lactate extraction ratio was negatively correlated with mixed
      venous plasma lactate (r2 = .50; p = .006). Hyperlactatemia, metabolic acidosis
      (SBD, >3.3), and acidemia (pH <7.35) were strongly positively associated with a
      fatal outcome (relative risks [95% confidence interval], 4.3 [range, 1.8-10.6],
      5.0 [range, 3.0-8.1], and 2.7 [range, 1.8-4.1], respectively). The SBD was the
      single best clinical or laboratory predictor of fatal outcome. The overall median
      lactate/pyruvate ratio was raised at 30.6 (range, 20.6-62.3; normal range, <15),
      suggesting hypoxia and anaerobic glycolysis, and was significantly higher in
      fatal cases (p < .0001). In an additive multivariate model, the two main
      independent contributors to metabolic acidosis were plasma creatinine, as a
      measure of renal dysfunction, and venous plasma lactate, together accounting for
      63% of the variance in SBD. In univariate analyses, they contributed 29% and 38%,
      respectively. CONCLUSIONS: These results confirm the importance of acidosis in
      the pathophysiology of severe adult malaria and suggest a multifactorial origin
      involving tissue hypoxia, liver dysfunction, and impaired renal handling of
      bicarbonate.

PMID- 10890630
TI  - Detection of false lumen perfusion at the beginning of cardiopulmonary bypass in
      patients undergoing repair of aortic dissection.
AB  - OBJECTIVE: In patients undergoing surgical repair of aortic dissection, false
      lumen perfusion during cardiopulmonary bypass may produce central nervous system
      damage, myocardial ischemia, aortic rupture, and death. We describe a method to
      detect false lumen perfusion at the beginning of retrograde aortic perfusion that
      may prevent these complications. DESIGN: Sonicated albumin microbubbles (8 mL)
      were injected through a side branch of the extracorporeal circulation line to
      detect true lumen and/or false lumen perfusion of the thoracic aorta at the
      beginning of cardiopulmonary bypass. Transesophageal echocardiography was used to
      image aortic perfusion. SETTING: The study was performed in a cardiac surgery
      theater. PATIENTS: A total of 27 consecutive patients undergoing operation for
      Type I aortic dissection were studied. INTERVENTIONS: All patients underwent
      surgical repair of aortic dissection and retrograde aortic perfusion through one
      femoral artery. MEASUREMENTS AND MAIN RESULTS: Patients were divided into three
      groups: Group I, those having adequate true lumen perfusion: brisk appearance and
      washout of contrast in the true lumen with no, poor, or delayed opacification of
      the false lumen; Group II, those having mixed true lumen and false lumen
      perfusion: simultaneous opacification of both lumens; Group III, those having
      inappropriate false lumen perfusion: same criteria as for adequate true lumen
      perfusion applied to the false lumen. The true lumen was perfused in 13 patients,
      both lumens in 11 patients, and false lumen alone in three patients. In these
      three patients, cannulation was repeated through the contralateral femoral artery
      with restoration of true lumen perfusion; the first patient died of diffuse
      cerebral ischemic damage and renal failure, another one experienced temporary
      postoperative monoparesis, and the last had no neurologic sequelae. CONCLUSIONS:
      Contrast echocardiography allows immediate detection of retrograde aortic
      perfusion during cardiopulmonary bypass and may help prevent neurologic
      complications and death in patients with Type I dissection.

PMID- 10890631
TI  - Whole blood tumor necrosis factor-alpha production and its relation to systemic
      concentrations of interleukin 4, interleukin 10, and transforming growth factor
      beta1 in multiply injured blunt trauma victims.
AB  - OBJECTIVE: To study the relation of whole blood endotoxin responsiveness to
      inhibitory mediators systemically released after severe blunt trauma. DESIGN:
      Prospective, observational study. SETTING: University trauma center. PATIENTS:
      Thirty-two patients with blunt trauma (mean injury severity score, 33 points).
      INTERVENTIONS: Standard emergency department, surgical care, and postoperative
      intensive care unit treatment. MEASUREMENTS AND MAIN RESULTS: Whole blood and
      serum were obtained immediately after admission to the emergency department (<8
      hrs after trauma, denoted day 0) and on days 1, 2, 4, 6, 8, and 14 after trauma.
      Whole blood specimens were assayed for endotoxin-induced tumor necrosis factor
      (TNF)-alpha synthesis ex vivo and serum specimen were assayed for interleukin
      (IL)-4, IL-10, and transforming growth factor (TGF)-beta1 concentrations.
      Moreover, the TNF-alpha inhibitory capacity of recombinant human (rh) IL-4, rhIL
      10, and TGF-beta1 as well as the inhibitory capacity of patients' serum from days
      0, 1, 2, 4, 6, 8, and 14 were tested on uninjured donors' whole blood. Cytokines
      were determined by ELISA. Whole blood endotoxin responsiveness in multiply
      injured patients was significantly reduced during the observation period and was
      found to be significantly related to the total inhibitory activity detected in
      the corresponding sera. Exchange of patients' serum for uninjured donors' or
      recovered patients' serum restored TNF-alpha production of peripheral blood
      mononuclear cells from multiply injured patients. Serum levels of IL-4 and IL-10
      were not related to trauma patients' whole blood TNF-alpha production upon
      endotoxin stimulation, whereas TGF-beta1 concentrations were positively related.
      Compared with the apparent half-maximal inhibition concentrations determined,
      serum levels of TGF-beta1, IL-10, and IL-4 were 20- to 20,000-fold below the
      quantities required to explain the inhibitory serum activity in multiply injured
      patients on day 0. CONCLUSIONS: Whole blood hyporesponsiveness to endotoxin in
      multiply injured patients is caused by soluble serum factors systemically
      released after trauma, whereas the intrinsic leukocyte function appears
      unaffected. Inhibitory mediators other than IL-4, IL-10, or TGF-beta1 are
      supposed to be of major biological relevance for the posttraumatic regulation of
      leukocyte function. Characterization of the causative suppressive mediators is
      supposed as a prerequisite for the development of immunologically based
      therapeutic approaches in critically ill patients.

PMID- 10890632
TI  - Endothelin in septic patients: effects on cardiovascular and renal function and
      its relationship to proinflammatory cytokines.
AB  - OBJECTIVE: To determine the time course of big-endothelin (big-ET) and its
      relationship to proinflammatory cytokines and organ function in sepsis. DESIGN:
      Prospective analysis in patients meeting criteria of severe sepsis as part of a
      multicenter study (RAMSES) with an anti-tumor necrosis factor monoclonal antibody
      F(ab')2 fragment (afelimomab). SETTING: University hospital intensive care unit.
      PATIENTS: A total of 23 nontrauma patients with severe sepsis or septic shock and
      ten multiple trauma patients. Septic patients were randomized for additional
      experimental treatment when initial interleukin (IL)-6 serum level was above 1000
      pg/mL. INTERVENTIONS: Randomized patients received 1.0 mg/kg afelimomab or
      placebo three times daily over 3 days in addition to standard treatment. In each
      patient, serial blood samples for plasma big-ET and cytokine determination as
      well as clinical data were collected over 28 days. MEASUREMENTS AND MAIN RESULTS:
      Significantly increased concentrations of circulating big-ET were found in
      patients with severe sepsis as compared with healthy subjects. In septic
      patients, big-ET plasma levels were higher than in multiple trauma patients, and
      were more elevated in randomized than in nonrandomized patients. At study entry
      (day 0), big-ET reached a peak concentration and significantly correlated with IL
      6 (r2 = .43) and IL-8 (r2 = .44) in patients with severe sepsis. Moreover, big-ET
      levels in septic patients, pooled over all observation days, correlated
      positively with pressure-adjusted heart rate, central venous pressure, pulmonary
      artery pressure, and pulmonary vascular resistance and correlated inversely with
      creatinine clearance (r2 = .54, .54, .59, .40, and .51, respectively, p = .0001).
      In all randomized septic patients, pressure-adjusted heart rate decreased from
      day 0 to day 2 in parallel with big-ET; however, a significant decrease in big-ET
      (day 0 to day 2) was only found in patients additionally treated with afelimomab.
      CONCLUSIONS: In patients with severe sepsis, big-ET plasma levels are markedly
      increased, even above those of multiple trauma patients, in close relationship to
      IL-6 and IL-8, and with significant correlation to renal function and pulmonary
      vascular tone.

PMID- 10890633
TI  - Increased circulating soluble intercellular adhesion molecule-1 in acute
      myocardial infarction: a possible predictor of reperfusion ventricular
      arrhythmias.
AB  - OBJECTIVES: Myocardial ischemia/reperfusion induces ventricular reperfusion
      arrhythmias (RAs). Significant parts of RAs are considered to be evoked by oxygen
      free radicals. Inasmuch as activated leukocytes release oxygen free radicals, and
      as the intercellular adhesion molecule-1 (ICAM-1) plays a major role in leukocyte
      infiltration, we examined whether there may be a relationship between plasma
      levels of soluble ICAM-1 (sICAM-1) and frequency of RAs in patients with acute
      myocardial infarction (AMI). DESIGN: Prospective study comparing the two AMI
      patient groups with or without RAs. SETTING: Coronary care unit and cardiac
      catheterization laboratories in a general hospital. PATIENTS: Twenty-three AMI
      patients (eight women and 15 men, aged 32 to 79 yrs). INTERVENTIONS: All patients
      received percutaneous balloon angioplasty with or without previous intracoronary
      thrombolysis. Significant RAs were defined as at least one of nonsustained
      ventricular tachycardia, multifocal premature ventricular contraction, and
      frequent premature ventricular contraction occurring >15 times/min, which were
      not observed before reperfusion. MEASUREMENTS AND MAIN RESULTS: Plasma sICAM-1
      levels were measured using an enzyme-linked immunosorbent assay. The plasma sICAM
      1 levels at admission were significantly greater in RA(+) (243 +/- 60 ng/mL) than
      RA(-) group (192 +/- 44 ng/mL) (p < .05). We followed plasma sICAM-1 levels up to
      3 wks, and found that sICAM-1 levels were consistently higher in the RA(+) than
      the RA(-) group. Simple regression analysis showed no significant relationship
      between plasma sICAM-1 levels and age, systolic and diastolic blood pressures, or
      serum creatine kinase activity. The two AMI groups showed no differences in age,
      gender, events of major coronary risk factors, preinfarction angina, and
      medication. CONCLUSIONS: The increase in the plasma levels of sICAM-1 was
      observed in patients manifesting ventricular RAs. This increase in sICAM-1 levels
      was observed as early as at admission. The increased plasma sICAM-1 levels may be
      a useful biochemical marker for predicting myocardial reperfusion injury such as
      RAs in AMI.

PMID- 10890634
TI  - Endotoxin promotes adhesion of human erythrocytes to human vascular endothelial
      cells under conditions of flow.
AB  - OBJECTIVE: To investigate the effects of endotoxin on adhesion of human red blood
      cells to human vascular endothelial cells under conditions of flow. DESIGN:
      Prospective, randomized, controlled in vitro study. SETTINGS: University
      affiliated cell biology laboratory. SUBJECTS: Human erythrocytes and human
      vascular endothelial cells. INTERVENTIONS: Fresh human erythrocytes and human
      vascular endothelial cells grown as monolayers were incubated with either saline
      or endotoxin. After incubation, endothelial monolayers were superfused with
      erythrocytes, and the number of erythrocytes adhering to the endothelial
      monolayer was quantified. MEASUREMENTS AND MAIN RESULTS: Adhesion of erythrocytes
      to vascular endothelium was measured under conditions of continuous flow in
      different settings: a) exposure of both endothelial cells and erythrocytes to
      saline; b) incubation of both erythrocytes and endothelial cells with endotoxin;
      c) exposure of erythrocytes only to endotoxin; d) incubation of endothelial cells
      only to endotoxin; and e) both the endothelial cells and erythrocytes incubated
      with different concentrations of endotoxin. Erythrocyte adhesion in the saline
      control group was 71 +/- 8 cells/mm2. Incubation of both components with
      endotoxin increased the number of adhesive erythrocytes to 172 +/- 9 cells/mm2 (p
      < .05). When only the endothelial cells were treated with endotoxin, 142 +/- 8
      cells/mm2 adhered to the endothelial monolayer, whereas the incubation of the
      erythrocytes only to endotoxin resulted in adhesion of 102 +/- 3 cells/mm2.
      Decreasing concentrations of endotoxin reduced adhesion from 172 +/- 9 cells/mm2
      (endotoxin, 75 microg/mL) to 165 +/- 9 cells/mm2 (endotoxin, 25 microg/mL), 153
      +/- 4 cells/mm2 (endotoxin, 1 microg/mL), and 146 +/- 6.1 cells/mm2 (endotoxin, 5
      ng/mL). CONCLUSIONS: Exposure of human erythrocytes and human venous vascular
      endothelial cells to an inflammatory stimulus such as endotoxin promotes a dose
      dependent adhesion of erythrocytes to endothelium in a dynamic environment. These
      adhesive erythrocyte-endothelium interactions can be produced by exposure of
      either red blood cells or endothelial cells to endotoxin, with a higher degree of
      adhesion after activation of the endothelial cell component.

PMID- 10890635
TI  - Thrombocytopenia and prognosis in intensive care.
AB  - OBJECTIVE: To study the incidence and prognosis of thrombocytopenia in adult
      intensive care unit (ICU) patients. DESIGN: Prospective observational cohort
      study. SETTING: The medical ICU of a university hospital and the combined medical
      surgical ICU of a regional hospital. PATIENTS: All patients consecutively
      admitted during a 5-month period. INTERVENTIONS: Patient surveillance and data
      collection. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was ICU
      mortality. Data of 329 patients were analyzed. Overall ICU mortality rate was
      19.5%. A total of 136 patients (41.3%) had at least one platelet count <150 x
      10(9)/L. These patients had higher Multiple Organ Dysfunction Score (MODS),
      Simplified Acute Physiology Score (SAPS) II, and Acute Physiology and Chronic
      Health Evaluation (APACHE) II scores at admission, longer ICU stay (8 [4-16] days
      vs. 5 [2-9] days) (median [interquartile range]), and higher ICU mortality (crude
      odds ratio [OR], 5.0; 95% confidence interval [CI], 2.7-9.1) and hospital
      mortality than patients with daily platelet counts >150 x 10(9)/L (p < .0005 for
      all comparisons). Bleeding incidence rose from 4.1% in nonthrombocytopenic
      patients to 21.4% in patients with minimal platelet counts between 101 x 10(9)/L
      and 149 x 10(9)/L (p = .0002) and to 52.6% in patients with minimal platelet
      counts <100 x 10(9)/L (p < .0001). In all quartiles of admission APACHE II and
      SAPS II scores, a nadir platelet count <150 x 10(9)/L was related with a
      substantially poorer vital prognosis. Similarly, a drop in platelet count to < or
      =50% of admission was associated with higher death rates (OR, 6.0; 95% CI, 3.0
      12.0; p < .0001). In a logistic regression analysis with ICU mortality as the
      dependent variable, the occurrence of thrombocytopenia had more explanatory power
      than admission variables, including APACHE II, SAPS II, and MODS scores (adjusted
      OR, 4.2; 95% CI, 1.8-10.2). CONCLUSIONS: Thrombocytopenia is common in ICUs and
      constitutes a simple and readily available risk marker for mortality, independent
      of and complementary to established severity of disease indices. Both a low nadir
      platelet count and a large fall of platelet count predict a poor vital outcome in
      adult ICU patients.

PMID- 10890636
TI  - Correlating the severity of paraquat poisoning with specific hemodynamic and
      oxygen metabolism variables.
AB  - OBJECTIVE: To investigate the hemodynamics and oxygen metabolism of patients with
      varying degrees of severity of paraquat poisoning. DESIGN: Prospective,
      observational, clinical study. SETTING: Intensive care unit in a university
      hospital. PATIENTS: Forty-three consecutive patients with paraquat and/or diquat
      poisoning were classified into three groups by the severity index of paraquat
      poisoning (SIPP; hr/mg/L). INTERVENTIONS: Standard treatments included specific
      respiratory management, fluid resuscitation, and aggressive circulatory support.
      MEASUREMENTS AND MAIN RESULTS: Serum paraquat and diquat levels were measured at
      arrival, and SIPP was calculated. The cardiac index (CI), left ventricular stroke
      work index (LVSWI), systemic vascular resistance index (SVRI), oxygen delivery
      index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER)
      were measured at 6, 12, 24, 36, 48, 72, and 96 hrs postadmission. A significant
      inverse correlation between SIPP and survival time was found in 31 fatal cases (r
      = .85; p < .001). In the SIPP 10-50 group, CI, DO2I, VO2I, and O2ER were
      maintained at higher levels than in the SIPP group of <10 (p < .05), whereas SVRI
      decreased significantly (p < .05). In the SIPP group of >50, CI, LVSWI, SVRI,
      DO2I, and VO2I decreased, whereas O2ER had a tendency to increase progressively.
      There was a significant correlation between SVRI and SIPP, O2ER and SIPP, and
      O2ER and SVRI 24 hrs after admission, respectively (p < .001). CONCLUSIONS:
      Paraquat poisoning is characterized by high oxygen consumption with high oxygen
      extraction, with the degree of derangement based on the severity index. The
      development of a marked imbalance between increased oxygen demand and decreased
      oxygen supply because of myocardial depression might be a possible cause of death
      in circulatory failure.

PMID- 10890637
TI  - Cellular signaling by the potent bronchoconstrictor endothelin-1 in airway smooth
      muscle.
AB  - OBJECTIVE: The objective of this study was to determine whether the potent
      bronchoconstrictor endothelin-1 was coupled to the activation of the inositol
      phosphate and/or inhibition of the cyclic adenine monophosphate second messenger
      pathways in porcine airway smooth muscle. DESIGN: Prospective, controlled, in
      vitro, nonblinded study. SETTING: University biochemical and molecular biological
      research laboratory. SUBJECTS: Pigs of both genders. INTERVENTIONS: Airway smooth
      muscle was dissected from the trachea of pigs exsanguinated under anesthesia.
      Airway smooth muscle from six animals preloaded with 3H-myoinositol was exposed
      to endothelin-1, carbachol (positive control) or vehicle for 30 mins. Some
      tissues were pretreated with antagonists selective for the ET(A) (BQ-485) and
      ET(B) (BQ-788) endothelin receptor subtypes. Newly synthesized 3H-inositol
      phosphates were recovered by column chromatography. Airway smooth muscle from an
      additional 7 pigs was homogenized and incubated in the presence of 32P-alpha
      adenosine triphosphate, guanosine triphosphate (GTP) and either carbachol or
      endothelin to measure the inhibitory influence of carbachol (positive control) or
      endothelin on GTP-stimulated adenylyl cyclase activity. Newly synthesized 32P
      cyclic adenosine monophosphate was isolated by sequential column chromatography
      over Dowex and alumina. MEASUREMENTS AND MAIN RESULTS: Total inositol phosphates
      increased in porcine airway smooth muscle in response to either carbachol or
      endothelin. The endothelin receptor antagonist BQ-485 (ET(A) selective) but not
      BQ-788 (ET(B) selective) dose-dependently inhibited endothelin-1 induced inositol
      phosphate accumulation. In adenylyl cyclase assays, carbachol (positive control),
      but not endothelin-1, significantly inhibited GTP-stimulated adenylyl cyclase
      activity. CONCLUSION: Endothelin-1 couples to the activation of the inositol
      phosphate pathway via the ET(A) receptor subtype but does not couple to
      inhibition of the adenylyl cyclase pathway in porcine airway smooth muscle. The
      potent bronchoconstrictive effects of endothelin likely involve the acute
      activation of the inositol phosphate pathway in airway smooth muscle.

PMID- 10890638
TI  - Diaspirin-crosslinked hemoglobin reduces mortality of severe hemorrhagic shock in
      pigs with critical coronary stenosis.
AB  - OBJECTIVE: To evaluate the effects of resuscitation with a 10% diaspirin
      crosslinked hemoglobin (DCLHb) solution on global hemodynamic variables, systemic
      and myocardial oxygen transport and tissue oxygenation, and contractile function
      of the left ventricle in an experimental model of severe hemorrhagic shock and
      critical stenosis of the left anterior descending coronary artery (LAD). DESIGN:
      Prospective, placebo-controlled, randomized study. SETTING: Experimental animal
      laboratory. SUBJECTS: A total of 20 anesthetized pigs. INTERVENTIONS: After
      implementation of a permanent critical LAD stenosis (ie, maintenance of basal
      blood flow but absence of reactive hyperemia after a 10-sec complete vessel
      occlusion), hemorrhagic shock (target mean aortic pressure, 45 mm Hg) was induced
      within 15 mins by programmed withdrawal of blood and maintained for 60 mins.
      Subsequently, the volume of plasma lost during hemorrhage was replaced by either
      a balanced electrolyte solution containing 10 g/dL DCLHb (DCLHb group; n = 10) or
      an 8 g/dL human albumin solution (HSA) oncotically matched to DCLHb (HSA group; n
      = 10). Data were collected immediately after the infusion of the different
      solutions and again after 60 mins had elapsed. MEASUREMENTS AND MAIN RESULTS:
      Although five of ten HSA-treated animals died of acute left ventricular failure
      within the first 20 mins after complete fluid resuscitation, all of the DCLHb
      treated animals survived the 60-min observation period after resuscitation (p <
      .05). This significant difference in mortality is explained by higher coronary
      perfusion pressure in DCLHb-treated animals (75 +/- 17 vs. 27 +/- 17 torr DCLHb
      vs. HSA group; p < .05) and persistence of subendocardial ischemia and hypoxia
      (radioactive microspheres method) in HSA-treated animals on resuscitation
      particularly affecting the LAD-supported myocardium (subendocardial oxygen
      delivery: 20 +/- 11 vs. 3 +/- 1 mL oxygen x g(-1) x min(-1), DCLHb vs. HSA group;
      p < .05). Except for enhanced myocardial contractility immediately on infusion of
      DCLHb (maximal left ventricular pressure increase: 2373 +/- 782 vs. 1730 +/- 543
      torr x sec(-1) DCLHb vs. HSA group; p < .05), no differences were detected
      between groups concerning the variables of systemic oxygen transport, tissue
      oxygenation, and regional contractile function of the myocardium (determined with
      microsonometry). CONCLUSIONS: Fluid resuscitation with 10% DCLHb solution
      completely reverses hemorrhagic shock-induced subendocardial ischemia and hypoxia
      in the presence of compromised coronary circulation and thereby prevents early
      death after resuscitation.

PMID- 10890639
TI  - Pentobarbital inhibits apoptosis in neuronal cells.
AB  - OBJECTIVE: Previous reports have demonstrated that barbiturates have a protective
      effect against cerebral ischemia, although the mechanisms are incompletely
      understood. Recently, it has been suggested that apoptosis is involved in
      ischemic neuronal death. This study examined the effect of pentobarbital on
      neuronal apoptosis. DESIGN: Randomized, controlled, prospective study. SETTING:
      University research laboratory. SUBJECTS: PC12 cells derived from rat
      pheochromocytoma as a model of neuronal tissue. INTERVENTIONS: Apoptosis was
      induced by depriving serum from the cell culture medium. Effect of pentobarbital
      (0.5, 5, 50 microg/mL) was evaluated. MEASUREMENTS AND MAIN RESULTS: First,
      electrophoresis of DNA and fluorescence microscopic examination were performed to
      ascertain whether apoptosis was really induced after serum deprivation in our
      cells. Second, the effect of pentobarbital on cytotoxicity (evaluated by a
      leakage assay of lactic dehydrogenase) was evaluated. Third, the percentage of
      apoptotic cells was calculated by measuring cellular DNA content with flow
      cytometry. Calculation of the percentage of apoptotic cells was based on
      cumulative frequency curves of the appropriate DNA histograms. DNA
      electrophoresis exhibited a typical ladder pattern from the first day after the
      induction of apoptosis. The cells with chromatin condensation and/or
      fragmentation increased day by day after depriving serum in fluorescence
      microscopic examination. Four days after the induction of apoptosis, cytotoxicity
      without pentobarbital was 53.9 +/- 24.3% (mean +/- SD). Pentobarbital
      significantly inhibited cell death in a dose-dependent fashion. The percentage of
      apoptotic cells without pentobarbital was 94.9 +/- 6.3% 4 days after the
      induction of apoptosis. The treatment with 50 microg/mL pentobarbital
      significantly decreased the percentage of apoptotic cells to 61.8 +/- 21.3%.
      CONCLUSIONS: Our data indicate that pentobarbital inhibits apoptosis induced by
      serum deprivation in PC12 cells.

PMID- 10890640
TI  - Treatment of acute hyponatremia: ensuring the excretion of a predictable amount
      of electrolyte-free water.
AB  - BACKGROUND: Hypertonic saline is the recommended therapy to shrink swollen brain
      cells in patients with acute hyponatremia accompanied by seizures. OBJECTIVES: In
      the absence of hypertonic saline, hypertonic mannitol will shrink the cell
      volume. Because mannitol is excreted rapidly, our aim was to ensure that it would
      be excreted with electrolyte-free water (EFW) and to evaluate the renal
      mechanisms responsible for EFW excretion. DESIGN: A randomized, prospective,
      placebo-controlled study in rats was carried out in a research laboratory.
      SUBJECTS: Adult male Wistar rats. INTERVENTIONS: The control group of rats (n =
      6) was administered hypotonic saline, a loop diuretic, vasopressin, and glucose
      by the intraperitoneal route; in the experimental group (n = 6), glucose was
      replaced with mannitol. Plasma electrolytes were measured at 0 and 210 mins, and
      balances for water, sodium, and potassium were obtained from 0 to 90 mins and
      from 90 to 210 mins. MEASUREMENTS AND MAIN RESULTS: Virtually 100% of the
      administered mannitol was excreted within 210 mins, and half was excreted in the
      first 90 mins. The urine contained EFW only in the mannitol group because of a
      larger volume in the first 90 mins (EFW, 3.7 mL) and to a lower excretion of NaCl
      in the next 120 mins (EFW, 3.5 mL). CONCLUSIONS: The combined use of mannitol and
      a loop diuretic caused the excretion of a predictable volume of EFW because the
      urine was iso-osmotic to plasma and contained all the administered mannitol. The
      calculated decrease in intracellular fluid volume was equivalent when mannitol
      was retained or excreted.

PMID- 10890641
TI  - Effect of lung water content, manipulated by intratracheal furosemide,
      surfactant, or a mixture of both, on compliance and viscoelastic tissue forces in
      lung-lavaged newborn piglets.
AB  - OBJECTIVE: To study the impact of lung water content and its reduction by a
      topically applied diuretic on respiratory and lung tissue mechanics in comparison
      with surfactant administration in surfactant-deficient newborn piglets with
      lavage-induced lung injury. DESIGN: Controlled, randomized study. SETTING: Animal
      research facility. SUBJECTS: Newborn piglets. TREATMENT Piglets were surfactant
      depleted by lung lavage and, after a pretreatment period, randomly treated with
      intratracheal furosemide, furosemide and surfactant, or with surfactant alone.
      MEASUREMENTS AND MAIN RESULTS: Dynamic compliance (C(DYN)), static compliance
      (C(ST)), stress-adaptation pressures (P(DIFF)) and post mortem lung water content
      were determined. Static compliance in the furosemide-surfactant group was not
      significantly higher than in the surfactant group. At the end of the study, C(ST)
      did not differ between the three groups because C(ST) in the furosemide group had
      increased to values similar to those of the surfactant-containing treatment
      groups: C(ST) F+S: 0.73 +/- 0.2 mL/cm H2O/kg body weight (BW); C(ST) S: 0.61 +/-
      0.11 mL/cm H2O/kg BW; and C(ST) F: 0.60 +/- 0.19 mL/cm H2O/kg BW). Compliance was
      inversely and P(DIFF) was directly correlated to lung water (LW) content (C(ST)
      vs. LW: r2 = .59, p = .001; C(DYN) vs. LW: r2 = .49, p = .006; P(DIFF) vs. LW: r2
      = .37, p = .059), independent of the type of treatment. Changes in C(ST) and
      C(DYN) were inversely related to changes in P(DIFF). Intrapulmonary furosemide
      was more rapidly absorbed when administered to the surfactant-depleted lung alone
      compared with the mixture with surfactant, and intrapulmonary furosemide had a
      rapid systemic effect. CONCLUSION: Although the combination of surfactant with a
      diuretic failed to increase respiratory compliance to a significantly larger
      extent than surfactant alone, furosemide at the end of the study increased
      respiratory compliance to a level similar to surfactant-containing treatments.
      Lung water content and, to a lesser extent, the absence or presence of surfactant
      appeared to determine lung mechanics, and its impact on lung mechanics was
      similar to surfactant administration.

PMID- 10890642
TI  - Oxygen-carrying capacity during 10 hours of hypercapnia in ventilated dogs.
AB  - OBJECTIVE: To test if a relatively long-term exogenous hypercapnia, equivalent to
      those maintained during permissive hypercapnia, can persistently increase oxygen
      carrying capacity in ventilated dogs. DESIGN: Prospective study. SETTING:
      Research laboratory in a hospital. SUBJECTS: Six mongrel dogs (3 males; 3
      females). INTERVENTIONS: The dogs were anesthetized (30 mg/kg pentobarbital,
      i.v.), intubated, and cannulated in one femoral artery, one femoral vein, and the
      right jugular vein. The mean arterial blood pressure, heart rate, and mean
      pulmonary artery pressure were continuously recorded. Anesthesia, fluid balance,
      and normothermia were maintained. Arterial hypercapnia was generated by the
      addition of 60 torr dry CO2 (8 kPa) to the inspired air for 10 hrs, continuously.
      All subjects were paralyzed (vecuronium bromide) and ventilated with room air,
      while the ventilator settings were kept constant. MEASUREMENTS AND MAIN RESULTS:
      Arterial and venous gas exchange profiles, hemoglobin concentration, oxygen
      saturation, oxygen content, cardiac output, and oxygen consumption were
      determined, before, during, and after 10 hrs of hypercapnia, periodically. Both
      hemoglobin concentration and oxygen content were gradually increased during
      hypercapnia and reached significant levels at 8 and 10 hrs of hypercapnia,
      respectively. These increases continued up to 2 hrs after termination of
      hypercapnia. The PaO2/FIO2, as an index of arterial oxygenation, was
      significantly increased during the first 3 hrs of hypercapnia and then remained
      at the normoxic level up to 10 hrs of hypercapnia. No significant changes
      occurred in the mean arterial blood pressure and oxygen consumption. The heart
      rate and cardiac output were significantly reduced at 4 and 8 hrs of hypercapnia,
      respectively. The mean pulmonary artery pressure was increased throughout the
      hypercapnic trial. CONCLUSIONS: A relatively long-term exogenous hypercapnia can
      significantly increase oxygen-carrying capacity in normal ventilated dogs.
      Whether this effect can occur during permissive hypercapnia because of controlled
      ventilation in patients warrants investigation.

PMID- 10890643
TI  - Liposome-encapsulated hemoglobin does not exacerbate endotoxin-induced lung
      injury.
AB  - OBJECTIVE: To test the hypothesis that liposome encapsulated hemoglobin (LEH), an
      experimental oxygen-carrying fluid, exacerbates endotoxin-induced lung injury in
      the rat. DESIGN: Prospective, randomized animal study. SETTING: University animal
      laboratory. METHODS: Anesthetized Sprague-Dawley rats (n = 8-13) were infused
      with LEH (10% of estimated total blood volume) or vehicle (0.9% NaCl). Thirty
      minutes later, Escherichia coli endotoxin (3.6 mg/kg, i.v.) or vehicle (0.9%
      NaCl) was administered, and skeletal muscle oxygen tension as well as lung injury
      were assessed at 2, 4, and 8 hrs. Oxygen tension was measured using a
      miniaturized thin film oxygen sensor placed in the rectus abdominis muscle, and
      lung injury was evaluated by determining lung weights, lung myeloperoxidase
      activity, lung tissue tumor necrosis factor-alpha level, and protein
      concentration in bronchoalveolar lavage fluid. RESULTS: The intravenous bolus
      injection of E. coli endotoxin elevated lung water content (33% +/- 5%; p < .01
      vs. sham controls), myeloperoxidase activity (56% +/- 6%; p < .01), and tumor
      necrosis factor-alpha production (1320 +/- 154 pg/g lung tissue; p < .05 vs.
      undetected levels in sham controls), as well as induced protein accumulation in
      bronchoalveolar lavage fluid (258% +/- 38%; p < .01) and skeletal muscle hypoxia
      (52 +/- 8 mm Hg; p < .05). Pretreatment with LEH, which when infused alone did
      not induce lung injury, had no effect on these responses. CONCLUSION: In this
      specific model of endotoxin-induced lung injury, LEH does not exacerbate
      microvascular leakage and leukosequestration, the hallmarks of adult respiratory
      distress syndrome.

PMID- 10890644
TI  - Adenosine and nitric oxide regulate regional vascular resistance via
      interdependent and independent mechanisms during sepsis.
AB  - OBJECTIVE: Adenosine receptor blockade increases regional resting vascular
      resistance during sepsis. In healthy subjects, part of adenosine's actions are
      mediated via stimulation of nitric oxide synthase. Because nitric oxide synthase
      activity is thought to be a major contributor to altered vascular tone in sepsis,
      we tested the hypothesis that some of the nitric oxide-mediated resting regional
      resistance during sepsis is secondary to endogenous adenosine stimulation of
      nitric oxide synthase. DESIGN: Prospective, randomized, controlled experiment.
      SETTING: Shock-trauma and basic science laboratory. SUBJECTS: Male Sprague-Dawley
      rats. INTERVENTIONS: Twenty-four hours after sepsis or sham induction, rats were
      separated into two groups (n = 6 to 10 in each group). Group 1 received a 10-min
      infusion of the adenosine antagonist 8-sulfophenyltheophylline (0.9 mg/kg x min)
      followed by a 10-min infusion of L-nitro-arginine-methyl ester (0.5 mg/kg x min).
      Group 2 similarly received L-nitro-arginine-methyl ester followed by 8
      sulfophenyltheophylline in the presence of L-nitro-arginine-methyl ester.
      MEASUREMENTS AND MAIN RESULTS: Hemodynamic and blood flow measurements
      (microspheres) were made before infusions, 10 mins after the administration of
      each single-agent infusion, and 10 mins after combined-agent infusions were
      administered. No significant resistance alterations were observed in nonseptic
      rats. In septic rats, adenosine receptor blockade alone increased
      hepatosplanchnic and skeletal muscle vascular resistance, but no further
      increases were seen when L-nitro-arginine-methyl ester was added. Nitric oxide
      synthase inhibition alone increased hepatosplanchnic and skeletal muscle vascular
      resistances. When 8-sulfophenyltheophylline was added to the infusion, skeletal
      muscle vascular resistance increased significantly more than with L-nitro
      arginine-methyl ester alone, but there were no further increases in
      hepatosplanchnic resistance. Renal and adipose vascular resistances increased
      with L-nitro-arginine-methyl ester infusions, and 8-sulfophenyltheophylline
      produced no effect. CONCLUSIONS: During sepsis, nitric oxide caused resting
      vasodilation independent of adenosine in the renal and adipose vasculature. In
      the hepatosplanchnic circulation, there is reciprocal adenosine-nitric oxide
      interaction in maintaining resting regional resistance. Skeletal muscle displayed
      a dual adenosine-mediated (nitric oxide-independent) and nitric oxide-mediated
      (adenosine receptors required) interaction to regulate resting resistance during
      sepsis. These data indicate that in the hepatosplanchnic and skeletal muscle
      vasculature, all of the resting nitric oxide-mediated vasodilation is secondary
      to endogenous adenosine action, but in adipose and renal vasculature, resting
      nitric oxide mediated vasodilation is independent of adenosine. Endogenous
      adenosine also appears to play a significant role in determining resting skeletal
      muscle resistance that is independent of nitric oxide synthase during sepsis.

PMID- 10890645
TI  - Respiratory comfort and breathing pattern during volume proportional assist
      ventilation and pressure support ventilation: a study on volunteers with
      artificially reduced compliance.
AB  - OBJECTIVE: To assess respiratory comfort and associated breathing pattern during
      volume assist (VA) as a component of proportional assist ventilation and during
      pressure support ventilation (PSV). DESIGN: Prospective, double-blind,
      interventional study. SETTING: Laboratory. SUBJECTS: A total of 15 healthy
      volunteers (11 females, 4 males) aged 21-31 yrs. INTERVENTIONS: Decreased
      respiratory system compliance was simulated by banding of the thorax and abdomen.
      Volunteers breathed via a mouthpiece with VA and PSV each applied at two levels
      (VA, 8 cm H2O/L and 12 cm H2O/L; PSV, 10 cm H2O and 15 cm H2O) using a positive
      end-expiratory pressure of 5 cm H2O throughout. The study was subdivided into two
      parts. In Part 1, volunteers breathed three times with each of the four settings
      for 2 mins in random order. In Part 2, the first breath effects of multiple,
      randomly applied mode, and level shifts were studied. MEASUREMENTS AND MAIN
      RESULTS: In Part 1, the volunteers were asked to estimate respiratory comfort in
      comparison with normal breathing using a visual analog scale. In Part 2, they
      were asked to estimate the change of respiratory comfort as increased, decreased,
      or unchanged immediately after a mode shift. Concomitantly, the respiratory
      pattern (change) was characterized with continuously measured tidal volume,
      respiratory rate, pressure, and gas flow. Respiratory comfort during VA was
      higher than during PSV. The higher support level was less important during VA but
      had a major negative influence on comfort during PSV. Both modes differed with
      respect to the associated breathing pattern. Variability of breathing was higher
      during VA than during PSV (Part 1). Changes in respiratory variables were
      associated with changes in respiratory comfort (Part 2). CONCLUSIONS: For
      volunteers breathing with artificially reduced respiratory system compliance,
      respiratory comfort is higher with VA than with PSV. This is probably caused by a
      better adaptation of the ventilatory support to the volunteer's need with VA.

PMID- 10890646
TI  - An improved clinically relevant sepsis model in the conscious rat.
AB  - OBJECTIVE: To develop an improved small animal experimental paradigm that more
      closely mimics human sepsis. DESIGN: Prospective, randomized, controlled animal
      study. SETTING: Medical school research laboratory. SUBJECTS: Male Sprague-Dawley
      rats (280-320 g). INTERVENTIONS: We monitored the hemodynamic, hematologic, and
      biochemical consequences of abdominal sepsis produced by intraperitoneal
      implantation of a fibrin clot containing Escherichia coli in conscious,
      antibiotic-treated, rats. MEASUREMENTS AND MAIN RESULTS: Similar to human sepsis,
      the implanted, infected clot (LD50 = 5-7 x 10(8) colony forming units/mL, n = 6)
      elevated cardiac index (>7% vs. sterile clot, p < .05, at 4 hrs), whereas mean
      arterial pressure and heart rate remained unaffected. The total peripheral
      resistance index and stroke volume index tended to decrease and increase,
      respectively. In contrast, an intravenous bolus injection of endotoxin (LD50 of
      E. coli lipopolysaccharide = 5.6 mg/kg, n = 7), the most commonly used sepsis
      model, induced profound hypodynamic responses manifested by a 27% decrease (vs.
      endotoxin vehicle, p < .01) in cardiac index, a 28% increase in the total
      peripheral resistance index (p < .01), and a 33% decrease in the stroke volume
      index (P < .01). The infectious peritonitis model also displayed dose-dependent
      thrombocytopenia (<61%, p < .05), leukopenia (<60%, p < .05), and mortality rate
      (50% at 5-7 x 10(8) colony forming units/mL, p < .05) with a minimally elevated
      serum tumor necrosis factor-alpha level (145 vs. 12 +/- 6 pg/mL in controls, p <
      .05). CONCLUSION: This rodent model of antibiotic-treated, intra-abdominal
      infection features key characteristics of clinical sepsis. Although the
      hyperdynamic response observed in septic patients undergoing resuscitation was
      not clearly elicited, this paradigm better mimics clinical sepsis compared with
      the commonly used endotoxin model. Thus, utilization of this paradigm may provide
      additional opportunities to explore mechanisms of sepsis and to examine novel
      therapeutics.

PMID- 10890647
TI  - Membrane-permeable radical scavenger, tempol, reduces multiple organ injury in a
      rodent model of gram-positive shock.
AB  - OBJECTIVE: An enhanced formation of reactive oxygen species contributes to the
      multiple organ dysfunction syndrome (MODS) caused by endotoxin. We have recently
      discovered that two cell wall components, namely lipoteichoic acid (LTA) and
      peptidoglycan (PepG) of the gram-positive bacterium, Staphylococcus aureus,
      synergize to cause shock and MODS in the rat. Here, we investigate the effects of
      a membrane-permeable radical scavenger (tempol) on the circulatory failure and
      MODS (kidney, liver, lung) caused by coadministration of LTA (3 mg/kg i.v.) and
      PepG (10 mg/kg i.v.) in the anesthetized rat. DESIGN: Prospective, randomized
      study. SETTING: University-based research laboratory. SUBJECTS: Thirty-four
      anesthetized, male Wistar rats. INTERVENTIONS: After surgical preparation,
      anesthetized rats were observed for 6 hrs. Control rats were given vehicle
      (control plus saline, 2 mL/kg bolus injection, followed by an infusion of 1.5
      mL/kg i.v., n = 6) or tempol (control plus tempol, 100 mg/kg i.v. bolus
      injection, followed by an infusion of 30 mg/kg i.v., n = 6). Gram-positive septic
      shock was induced by coadministration of LTA (3 mg/kg i.v.) and PepG (10 mg/kg
      i.v.) (LTA/PepG plus saline, n = 12). Another group of rats was pretreated with
      tempol before shock was induced (LTA/PepG plus tempol, 100 mg/kg i.v. bolus
      injection, 15 mins before LTA/PepG administration, followed by an infusion of 30
      mg/kg i.v., n = 10). MEASUREMENTS AND MAIN RESULTS: Within 6 hrs, administration
      of LTA/PepG resulted in hypotension, acute renal dysfunction, hepatocellular
      injury, pancreatic injury, and increased plasma concentrations of
      nitrite/nitrate. Pretreatment of rats with tempol augmented the hypotension but
      attenuated the renal dysfunction and the hepatocellular injury/dysfunction caused
      by LTA/PepG. Tempol did not affect the increase in nitrite/nitrate caused by
      LTA/PepG. CONCLUSIONS: These results imply that an enhanced formation of reactive
      oxygen species (including superoxide anions) contributes to the kidney and liver
      injury and dysfunction caused by LTA/PepG in the anesthetized rat.

PMID- 10890649
TI  - Intravenous crocetinate prolongs survival in a rat model of lethal hypoxemia.
AB  - OBJECTIVE: To examine whether a carotenoid, trans-sodium crocetinate, has
      beneficial effects on hemodynamic status and short-term outcome in a rat model of
      lethal hypoxemia. DESIGN: Randomized, placebo-controlled study. SETTING: Medical
      school laboratory. SUBJECTS: Eighteen spontaneously breathing, anesthetized
      Sprague-Dawley rats (six per group). INTERVENTIONS: Rats underwent
      instrumentation to measure blood pressure, aortic and renal blood flow, arterial
      blood gases, bladder epithelial oxygen tension (by an intraluminal Clark
      electrode), and hepatic microvascular oxygen tension (measured by porphyrin
      phosphorescence). After stabilization, the rats were subjected to breathing 10%
      inspired oxygen concentration. After 10 mins, they were administered 1.25 mL/kg
      intravenous boluses of either isotonic saline (control), normal strength
      crocetinate (40 microg/mL), or a concentrated crocetinate solution (60
      microg/mL). These boluses were repeated at 30-min intervals until either death or
      3 hrs had elapsed. MEASUREMENTS AND MAIN RESULTS: With the onset of hypoxemia, we
      observed a rapid reduction in blood pressure and renal blood flow, maintenance of
      aortic blood flow, an increase in arterial base deficit, and falls in oxygen
      tensions in arterial blood, bladder epithelium, and hepatic microvasculature. A
      progressive deterioration in the control rats was noted, with only two of the six
      animals surviving for 3 hrs. However, all 12 rats in the two crocetinate groups
      survived for 3 hrs, with hemodynamic stability until 150 mins and a slow decline
      thereafter. CONCLUSIONS: Trans-sodium crocetinate improved hemodynamic status and
      prolonged survival in this model of severe acute hypoxic hypoxia. To our
      knowledge, this is the first demonstration of an intravenous agent having such an
      effect.

PMID- 10890648
TI  - The role of tumor necrosis factor in the development of multiple organ failure in
      a murine model.
AB  - OBJECTIVE: To elucidate the role of tumor necrosis factor (TNF) in the
      development of multiple organ dysfunction syndrome (MODS) after zymosan-induced
      peritonitis in mice. DESIGN: Prospective controlled laboratory study on zymosan
      induced generalized inflammation in mice. Over < or =28 days, a single
      intraperitoneal administration of zymosan induced a three-phase illness in C57BL
      mice, rendering them very ill with MODS-like symptoms from day 7 onward.
      Additionally, the same experiment was performed on C57BL/6 TNF-Rc-p55 knockout
      mice to elucidate the role of TNF and its receptor p55. SETTING: Animal research
      laboratory. SUBJECTS: Inbred C57BL mice and C57BL p55-/- mice received a single
      sterile intraperitoneal injection of zymosan suspended in paraffin oil (0.75 mg/g
      of body weight). MEASUREMENTS AND MAIN RESULTS: The animals were monitored for
      survival, condition, and body weight for < or =28 days. At 3, 7, 14, and 28 days
      after zymosan administration, bronchoalveolar lavage was performed and lungs and
      livers were extracted for isolation of RNA and histopathologic evaluation.
      Reverse-transcriptase-polymerase chain reaction was performed to quantify TNF
      alpha messenger RNA (mRNA) in the respective organs. Both animal strains went
      through initial shock with a high mortality rate during the first 3 days. The
      C57BL mice developed MODS with typical symptoms and histopathologic results
      correlating with excessive TNF-alpha mRNA expression from day 7 onward. In
      contrast, no disease, histopathologic changes, nor TNF-alpha mRNA expression in
      liver or lung was found within the TNF-Rc-p55-/- mice. CONCLUSION: Organ-derived
      TNF-alpha plays a crucial role in the development of MODS in this murine model.

PMID- 10890650
TI  - Attenuation of hyperoxia-induced diaphragmatic dysfunction with lidocaine in
      hamsters.
AB  - OBJECTIVE: Toxic free radicals cause dysfunction of respiratory muscles, probably
      leading to respiratory distress. Exposure to high concentrations of oxygen
      generates plenty of free radicals. Lidocaine scavenges the reactive molecules.
      The purposes of the current study were first to examine whether hyperoxia impairs
      diaphragmatic function, and second, to assess the effects of lidocaine on
      hyperoxia-induced diaphragmatic dysfunction, if developed. DESIGN: Prospective,
      randomized animal study. SETTING: University research laboratory. SUBJECTS: Forty
      and 48 adult male Golden-Syrian hamsters (110-150 g) in parts I and II studies,
      respectively. INTERVENTION: In the part I study, hyperoxia for 5 and 6 days
      reduced diaphragmatic contractility and enhanced fatigue. In the part II study,
      hamsters were randomly allocated to one of six groups (n = 8 each): exposure to
      air for 6 days with saline (group A-S) or lidocaine infusion (group A-L),
      exposure to 100% oxygen for 5 days with saline (group 05-S) or lidocaine (group
      05-L), and exposure to 100% oxygen for 6 days with saline (group 06-S) or
      lidocaine (group 06-L). Saline or lidocaine (2 mg/kg/hr) was subcutaneously given
      immediately before exposure to air or oxygen. Diaphragmatic contractility and
      fatigability were assessed in vitro using muscle strips excised from the costal
      diaphragms. Diaphragmatic levels of malondialdehyde (MDA), an index of free
      radical-mediated lipid peroxidation, were measured. These variables were compared
      between groups. MEASUREMENTS AND MAIN RESULTS: Twitch and tetanic tensions in
      groups 05-S and 06-S were reduced compared with group A-S. Tensions generated
      during fatigue trials were also decreased in groups 05-S and 06-S. MDA levels
      were elevated in diaphragms from these groups. In groups 05-L and 06-L,
      contractile dysfunction, deterioration of fatigability, and MDA formation in the
      diaphragm were attenuated. CONCLUSIONS: Lidocaine attenuated hyperoxia-induced
      diaphragmatic dysfunction assessed by contractile profiles and fatigability in
      hamsters. This beneficial effect may be attributable, in part, to inhibition of
      lipid peroxidation.

PMID- 10890651
TI  - Effect of dopexamine on intestinal tissue concentrations of high-energy
      phosphates and intestinal release of purine compounds in endotoxemic rats.
AB  - OBJECTIVES: To determine the effect of dopexamine, a synthetic catecholamine
      ligand for dopaminergic and beta2-adrenergic receptors, on intestinal release of
      adenosine 5'-triphosphate (ATP) degradation products and on intestinal tissue
      concentrations of high-energy phosphates during endotoxemia. DESIGN: Randomized,
      controlled trial. SETTING: Experimental laboratory. SUBJECTS: Twenty-one male
      Wistar rats. INTERVENTIONS: Rats given endotoxin (Escherichia coli
      lipopolysaccharide [LPS]; 1.5 mg/kg i.v. over 60 mins) were treated with a
      continuous infusion of dopexamine (DPX; 2.5 microg/kg/min, n = 7, group LPS +
      DPX) or 0.9% saline (n = 7, group LPS) during a study period of 120 mins. Animals
      in the control group (n = 7) received a volume-equivalent infusion of 0.9% saline
      without endotoxin. MEASUREMENTS AND MAIN RESULTS: In all groups, arterial and
      portal venous concentrations of adenosine, hypoxanthine, and uric acid were
      measured at baseline and at 60 and 120 mins after the endotoxin challenge, and we
      calculated the portal venous/arterial concentration differences as an indicator
      of the intestinal release of the purine compounds. Furthermore, at the end of the
      study, the intestinal tissue concentrations of the high-energy phosphates ATP,
      adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), creatine
      phosphate, and adenosine were determined, and we calculated the adenine
      nucleotide pool, the ATP/ADP and AMP/adenosine ratios, and the adenylate energy
      charge of the intestinal tissue. Endotoxemia decreases intestinal tissue ATP,
      ADP, AMP, and creatine phosphate concentrations, increases tissue adenosine
      content, and increases the release of hypoxanthine and uric acid from the
      intestinal tract. Dopexamine attenuates the endotoxin-induced decrease of the
      intestinal tissue adenine nucleotide pool, the AMP/adenosine ratio, and the
      release of the ATP-degradation products hypoxanthine and uric acid from the
      intestinal tract. CONCLUSIONS: Normotensive endotoxemia is associated with a
      deterioration of the intestinal energy balance and an increased release of ATP
      degradation products, indicating intestinal tissue ischemia. Furthermore, these
      results suggest the beneficial effects of dopexamine on pathophysiologic
      alterations of the intestinal energy metabolism during endotoxemia.

PMID- 10890652
TI  - A comparison of bolus versus continuous cardiac output in an experimental model
      of heart failure.
AB  - OBJECTIVE: The majority of studies examining cardiac output measurement have been
      done in physiologically stable models with low thermal background noise. Research
      comparing continuous cardiac output (CCO) with bolus thermodilution cardiac
      output (COTD) measures in human and animal models have reported high
      correlations, negligible bias, but large limits of agreement. The purpose of this
      project was to compare CCO with COTD measures in an experimental model of heart
      failure where the cardiac output values were low and the range was narrow.
      DESIGN: A one-group experimental design with preintervention control measures and
      repeated CCO and COTD measures across nine time points. SETTING: Cardiovascular
      research laboratory. SUBJECTS: Thirty dogs. MEASURES AND MAIN RESULTS: Univariate
      and multivariate versions of repeated-measures analysis were used to assess the
      influences of temperature, weight, and stage of the experimental protocol on CCO,
      COTD, and the differences between them. The two measures CCO and COTD were
      assessed for agreement by using methods proposed by Bland and Altman. Two hundred
      and fifty pairs of measurements were obtained during sinus rhythm. The range for
      COTD measures was 0.5-4.67 L/min and for CCO measures 1.0-5.40 L/min. Of the 250
      cardiac outputs estimated by the continuous method, 73.4% of the values were
      within +/-15% of that estimated by the repetitive, single thermodilution method.
      The mean bias for the entire protocol was 0.01 (SD = 0.51) with a range of 4.33
      L/min. CONCLUSION: Agreement between the two measures may be the function of
      biological variability, responses to anesthesia, and technique. Bland and Altman
      evaluation demonstrated low bias and precision and similar levels of agreement
      when compared with previous studies in an experimental model where the cardiac
      output was low and the range was narrow.

PMID- 10890653
TI  - The effect of mild endotoxemia during low arginine plasma levels on organ blood
      flow in rats.
AB  - OBJECTIVE: Arginine is the sole precursor in the generation of the vasodilating
      agent nitric oxide. Arginine plasma levels are low in situations associated with
      endotoxemia such as major trauma, sepsis, and experimental obstructive jaundice.
      The aim of the study was to evaluate hemodynamics at low arginine plasma levels
      during a low-grade endotoxemia. DESIGN: Randomized, placebo-controlled animal
      laboratory investigation. SUBJECTS: Male Wistar rats (n = 29), anesthetized.
      INTERVENTIONS: Rats were randomly assigned to receive (at t = 0 mins) an
      intravenous infusion of 1.5 mL of 0.9% NaCl (SAL, n = 12) or 1.5 mL of an
      arginase (3200 IU) solution (ASE, n = 17) over a 20-min period. After the SAL or
      ASE infusion, rats were randomly assigned to receive an intravenous endotoxin
      (lipopolysaccharide [LPS], 150 microg/kg in 1.0 mL of 0.9% NaCl; ASE/LPS, n = 10
      and SAL/LPS, n = 6) challenge or a control infusion (1.0 mL of 0.9% NaCl;
      ASE/SAL, n = 7 and SAL/SAL, n = 6) at t = 30 mins. MEASUREMENTS AND MAIN RESULTS:
      Organ blood flow was measured at t = 270 mins, using radiolabeled microspheres.
      At this time point, arginine plasma levels were lower in the ASE-treated rats
      (ASE/SAL vs. SAL/SAL and ASE/LPS vs. SAL/LPS, both p < .005, respectively).
      Cardiac output, mean arterial pressure, and therefore total peripheral resistance
      were similar for all groups. In the LPS-treated animals (SAL/LPS and ASE/LPS),
      cardiac output was maintained by a higher heart rate compensating the lower
      stroke volume. Organ blood flow to the small intestine and splanchnic blood flow
      was lower in the ASE/LPS-treated rats (both p < .05 when compared with other
      groups). Total liver blood flow was similar for all groups; the lower splanchnic
      blood flow was compensated for by a higher hepatic arterial blood flow.
      CONCLUSION: The present study shows that low arginine plasma levels do not
      influence organ blood flow, whereas, during a low-grade endotoxemia, low arginine
      plasma levels result in reduced blood flow to the small intestine.

PMID- 10890654
TI  - Relationship between arterial, mixed venous, and internal jugular
      carboxyhemoglobin concentrations at low, medium, and high concentrations in a
      piglet model of carbon monoxide toxicity.
AB  - OBJECTIVE: This study tested the hypothesis that mixed venous carboxyhemoglobin
      concentrations (V-COHb) and internal jugular carboxyhemoglobin concentrations (I
      COHb) accurately predict arterial carboxyhemoglobin concentrations (A-COHb). In
      addition, this study tested the hypothesis that there is a high correlation at
      low (COHb, 0% to 10%), moderate (COHb, >10% to 40%), and high (COHb, >40%)
      concentrations between V-COHb, I-COHb, and A-COHb. DESIGN: The study was a
      prospective comparison of A-COHb, V-COHb, and I-COHb concentrations in piglets
      exposed to increasing concentrations of carbon monoxide over 6 hrs to achieve a
      concentration of > or =60% COHb. Carboxyhemoglobin measurements were evaluated by
      analysis of variance and correlation analysis. Agreement between V-COHb and A
      COHb concentrations was examined by using a plot of arteriovenous differences
      against the mean of the two measurements. INTERVENTION: We simultaneously sampled
      arterial, mixed venous, and internal jugular blood every 30 mins over the 6-hr
      study period. RESULTS: Two hundred fifty arterial and mixed venous COHb
      concentrations were obtained, and 214 internal jugular COHb concentrations were
      obtained. One hundred additional arterial, mixed venous, internal jugular, and
      peripheral COHb concentrations were obtained. Correlation between samples at each
      concentration revealed r2 > = .94. CONCLUSION: Venous COHb concentrations predict
      arterial COHb concentrations with a high degree of accuracy and are correlated at
      low, moderate, and high concentrations of carbon monoxide exposure. Arterial or
      venous samples can be used to accurately measure COHb concentrations.

PMID- 10890655
TI  - Depletion of liver glutathione potentiates the oxidative stress and decreases
      nitric oxide synthesis in a rat endotoxin shock model.
AB  - OBJECTIVE: To verify the effects of liver glutathione depletion on redox status
      and nitric oxide system in a rat endotoxic shock model. DESIGN: Prospective,
      randomized, controlled study on rats. SETTING: A cardiocirculatory research
      laboratory. SUBJECTS: A total of 28 Sprague-Dawley male rats (200-250 g body
      weight) were divided into four experimental groups. INTERVENTIONS: Arterial
      blood, liver, and lung samples were taken from each animal under sodium
      pentobarbital (40 mg/kg i.p.) anesthesia 4 hrs after lipopolysaccharide (LPS
      group: 5 mg/kg i.p.; n = 7) or vehicle (control group: isotonic NaCl sterile
      solution i.p.; n = 7) treatments. Phorone (250 mg/kg i.p.) was injected to
      deplete glutathione in another two experimental groups of rats 30 mins before LPS
      (phorone+LPS group; n = 7) or vehicle (phorone group; n = 7) treatments, and 4
      hrs later the same samples as in LPS and control groups were taken under
      anesthesia. MEASUREMENTS AND MAIN RESULTS: Compared with the control group, the
      LPS group presented higher plasma concentration of end products of nitric oxide
      metabolism nitrites/nitrates, higher lung activity of inducible nitric oxide
      synthase, and oxidative stress defined by increased plasma concentration of the
      lipid peroxides malonaldehyde and 4-hydroxynonenal, and decreased plasma total
      antioxidant capacity. Treatment with phorone depleted liver glutathione (80% to
      90%). In the liver glutathione-depleted animals, the oxidative stress induced by
      LPS was potentiated and blunted the increases in inducible nitric oxide synthase
      and plasma nitrites/nitrates. CONCLUSION: These results show that depletion of
      the liver glutathione increases the oxidative stress and decreases nitric oxide
      synthesis of LPS-induced shock in rats.

PMID- 10890656
TI  - Norepinephrine and N(G)-monomethyl-L-arginine in hyperdynamic septic shock in
      pigs: effects on intestinal oxygen exchange and energy balance.
AB  - OBJECTIVES: To compare the effects of norepinephrine (NOR) and the nonselective
      nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), on
      intestinal blood flow, oxygen exchange, and energy metabolism over 24 hrs of
      hyperdynamic, normotensive porcine endotoxic shock. DESIGN: Prospective,
      randomized, experimental study with repeated measures. SETTING: Investigational
      animal laboratory. SUBJECTS: Twenty-seven pigs were divided into three groups:
      seven animals received no vasopressor therapy (ETX) during endotoxic shock; ten
      animals were treated with NOR; and ten animals were treated with L-NMMA.
      INTERVENTIONS: Pigs were anesthetized, mechanically ventilated, and instrumented.
      Eight hours later, endotoxic shock was initiated by an infusion of Escherichia
      coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to
      maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60
      mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was
      administered for 12 hrs in the treatment groups to maintain a MAP at preshock
      levels. MEASUREMENTS AND MAIN RESULTS: ETX caused a continuous fall in MAP,
      despite a sustained increase in the cardiac output achieved by fluid
      resuscitation. NOR maintained MAP at preshock levels because of a further rise in
      cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from
      systemic vasoconstriction. NOR increased portal venous blood flow concomitant
      with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither
      portal venous blood flow nor intestinal oxygen extraction. Mean capillary
      hemoglobin oxygen saturation of the ileal mucosa as well as the frequency
      distributions reflecting microcirculatory oxygen availability remained unchanged
      as well. Nevertheless, portal venous pH similarly decreased and portal venous
      lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal
      PCO2 gap progressively increased in the ETX and L-NMMA groups, whereas NOR
      blunted this response. CONCLUSIONS: Neither treatment could reverse the ETX
      induced derangements of cellular energy metabolism as reflected by the increased
      portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal
      mucosal acidosis was possibly caused by a different pattern of blood flow
      redistribution compared with L-NMMA.

PMID- 10890657
TI  - Pretreatment with tumor necrosis factor-alpha attenuates arterial hypotension and
      mortality induced by endotoxin in pigs.
AB  - OBJECTIVE: Tumor necrosis factor (TNF)-alpha administration in large amounts can
      induce a state of shock similar to that seen during severe sepsis. The objective
      of this study was to determine whether small doses of TNF-alpha might decrease
      the disposition for the development of shock induced by a subsequent infusion of
      endotoxin and to determine whether the mechanism of this protective effect of TNF
      alpha pretreatment could be associated with up-regulation of the anti
      inflammatory cytokine interleukin (IL)-10. DESIGN: Prospective, randomized,
      experimental study. SETTING: Investigative intensive care unit at an academic
      medical center. SUBJECTS: A total of 14 female Yorkshire pigs, weighing 20-25 kg.
      INTERVENTIONS: We studied two groups of animals-pigs treated with 500 ng/kg
      recombinant porcine TNF-alpha (n = 7) and pigs given diluent alone (n = 7). At 24
      hrs after treatment, both groups of pigs were subjected to a 24-hr continuous
      infusion of lipopolysaccharide (LPS) at a rate of 80 ng/kg/min. MEASUREMENTS AND
      MAIN RESULTS: The mortality rate was determined in both groups. Hemodynamic
      indices, oxygen transport variables, total and differential white cell counts,
      and serum concentrations of TNF and IL-10 were determined at frequent intervals
      before and after TNF-alpha administration and during the LPS infusion.
      Additionally, peripheral blood mononuclear cells were collected for determination
      of messenger ribonucleic acid expression of IL-10 by reverse transcription
      polymerase chain reaction. The administration of TNF-alpha at the dose used in
      this study did not have any profound effect. No pig treated with TNF-alpha died
      in response to the LPS infusion. In contrast, three of seven control pigs died
      during the LPS infusion. Lipopolysaccharide-induced arterial hypotension and
      arterial hypoxemia were attenuated in the TNF-alpha-treated group. Both groups
      had significant increases in serum concentrations of TNF-alpha in response to
      LPS, with no significant difference in peak serum TNF-alpha between groups.
      Neither serum concentrations of IL-10 nor expression of IL-10 messenger
      ribonucleic acid in circulating mononuclear cells differed between groups.
      CONCLUSIONS: The administration of TNF-alpha attenuated the severity of
      hyperdynamic shock induced by a subsequent infusion of endotoxin. This effect
      could not be associated with increased expression or elaboration of the anti
      inflammatory cytokine IL-10.

PMID- 10890658
TI  - Hypomagnesemia and hypophosphatemia at admission in patients with severe head
      injury.
AB  - OBJECTIVE: Low serum levels of electrolytes such as magnesium (Mg), potassium
      (K), calcium (Ca), and phosphate (P) can lead to a number of clinical problems in
      intensive care unit (ICU) patients, including hypertension, coronary
      vasoconstriction, disturbances in heart rhythm, and muscle weakness. Loss of
      these electrolytes can be caused, among other things, by increased urinary
      excretion. Cerebral injury can lead to polyuresis through a variety of
      mechanisms. We hypothesized that patients with cranial trauma might be at risk
      for electrolyte loss through increased diuresis. The objective of this study was
      to assess levels of Mg, P, and K at admission in patients with severe head
      injury. DESIGN: We measured plasma levels of Mg, P, K, Ca, and sodium at
      admission in 18 consecutive patients with severe head injury admitted to our ICU
      (group 1). As controls, we used 19 trauma patients with two or more bone
      fractures but no significant cranial trauma (group 2). SETTING: University
      teaching hospital. PATIENTS: Eighteen patients with severe head injury admitted
      to our surgical ICU (group 1) and 19 controls (trauma patients with no
      significant cranial trauma; group 2). MAIN RESULTS: Electrolyte levels at
      admission (group 1 vs. group 2; mean +/- SD, units: mmol/L) were as follows. Mg,
      0.57 +/- 0.17 (range, 0.24-0.85) vs. 0.88 +/- 0.21 (range, 0.66-1.42 mmol/L; p <
      .01). P, 0.56 +/- 0.15 (range, 0.20-0.92) vs. 1.11 +/- 0.15 (range, 0.88-1.44
      mmol/L; p < .01). K, 3.54 +/- 0.59 (range, 2.4-4.8) vs. 4.07 +/- 0.45 (range, 3.6
      4.8 mmol/L; p < .02). Ca, 2.02 +/- 0.24 (range, 1.45-2.51) vs. 2.14 +/- 0.20
      (range, 1.88-2.46; p = NS). In group 1, 12/18 patients had Mg levels <0.70 mmol/L
      vs. 2/19 patients in group 2 (p < .01); in group 1, 11/18 patients had P levels
      below 0.60 mmol vs. 0/19 patients in group 2 (p < .01). Moderate hypokalemia (K
      levels, <3.6 mmol/L) was present in 8/18 patients in group 1 vs. 1/19 patients in
      group 2 (p < .01). Severe hypokalemia (K levels, < or =3.0) was present in 4/18
      patients in group 1 vs. 0/19 patients in group 2 (p < .05). CONCLUSION: We
      conclude that patients with severe head injury are at high risk for the
      development of hypomagnesemia, hypophosphatemia, and hypokalemia. One of the
      causes of low electrolyte levels in these patients may be an increase in the
      urinary loss of various electrolytes caused by neurologic trauma. Mannitol
      administration may be a contributing factor. Intensivists should be aware of this
      potential problem. If necessary, adequate supplementation of Mg, P, K, and Ca
      should be initiated promptly.

PMID- 10890659
TI  - Prediction of nosocomial sepsis in neonates by means of a computer-weighted
      bedside scoring system (NOSEP score)
AB  - OBJECTIVE: To develop an easy-to-use bedside scoring system, composed of clinical
      variables, hematologic variables, and risk factors of infection, to predict
      nosocomial sepsis in neonatal intensive care unit patients. SETTING: A neonatal
      intensive care unit in a university hospital, Antwerp, Belgium. PATIENTS: Over 2
      yrs, we analyzed two groups of patients. First, we prospectively studied 104
      episodes of presumed nosocomial sepsis in 80 neonates (derivation cohort), and
      then we retrospectively studied 50 episodes in 39 neonates (validation cohort).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed two versions of
      a scoring system to predict nosocomial sepsis in sick neonates. The first scoring
      system (NOSEP-1 score) was based on 15 clinical, 12 laboratory, and 17 historical
      variables potentially connected with infection; the second one (NOSEP-2 score)
      also included the culture results of central vascular catheters. Based on the
      odds ratios of all independent variables, an additive and weighted score was
      developed and validated in a cohort of 39 patients screened for nosocomial sepsis
      in the same center. The NOSEP-1 score consisted of three laboratory variables (C
      reactive protein > or =14 mg/L, thrombocytopenia <150 x 10(9)/L, and neutrophil
      fraction >50%), one clinical factor (fever >38.2 degrees C [100.8 degrees F]),
      and one risk factor (parenteral nutrition for > or =14 days). The NOSEP-2 score
      consisted of the same variables plus catheter-hub and catheter insertion site
      colonization data. Receiver operating characteristic curve analysis demonstrated
      good predictor performance of the NOSEP-1 score (area under the curve [Az] = 0.82
      +/- 0.04 [SEM]) and NOSEP-2 score (Az = 0.84 +/- 0.04, p < .05). We checked
      whether a complex computer-generated scoring system (CD-1 and CD-2 scores) based
      on the original numerical values of the items used in NOSEP-1 and NOSEP-2 would
      improve the prediction of nosocomial sepsis. The analysis showed the accuracy of
      bedside NOSEP-1 and NOSEP-2 scores to be comparable with the more cumbersome
      computer-generated CD-1 and CD-2 scores (receiver operating characteristic curve,
      Az: CD-1 score = 0.81 +/- 0.04, p = .69, and CD-2 score = 0.86 +/- 0.04, p =
      .96). Finally, in the validation cohort, we showed that the developed scoring
      system has a good prediction potential for nosocomial sepsis (Hosmer-Lemeshow
      goodness-of-fit test, chi2 [19] = 16.34, p > .75). CONCLUSIONS: The simple
      bedside scoring system NOSEP-1 composed of C-reactive protein, neutrophil
      fraction, thrombocytopenia, fever, and prolonged parenteral nutrition exposure
      provides a valuable tool for early identification of nosocomial sepsis. Its
      predictive power can be improved by adding central vascular catheter insertion
      site and hub colonization to the score.

PMID- 10890660
TI  - Deadspace to tidal volume ratio predicts successful extubation in infants and
      children.
AB  - OBJECTIVE: Using a modification of the Bohr equation, single-breath carbon
      dioxide capnography is a noninvasive technology for calculating physiologic dead
      space (V(D)/V(T)). The objective of this study was to identify a minimal
      V(D)/V(T) value for predicting successful extubation from mechanical ventilation
      in pediatric patients. DESIGN: Prospective, blinded, clinical study. SETTING:
      Medical and surgical pediatric intensive care unit of a university hospital.
      PATIENTS: Intubated children ranging in age from 1 wk to 18 yrs. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Forty-five patients were identified by the
      pediatric intensive care unit clinical team as meeting criteria for extubation.
      Thirty minutes before the planned extubation, each patient was begun on pressure
      support ventilation set to deliver an exhaled tidal volume of 6 mL/kg. After 20
      mins on pressure support ventilation, an arterial blood gas was obtained,
      V(D)/V(T) was calculated, and the patient was extubated. Over the next 48 hrs,
      the clinical team managed the patient without knowledge of the preextubation
      V(D)/V(T) value. Of the 45 patients studied, 25 had V(D)/V(T) < or =0.50. Of
      these patients, 24 of 25 (96%) were successfully extubated without needing
      additional ventilatory support. In an intermediate group of patients with
      V(D)/V(T) between 0.50 and 0.65, six of ten patients (60%) successfully extubated
      from mechanical ventilation. However, only two of ten patients (20%) with a
      V(D)/V(T) > or =0.65 were successfully extubated. Logistic regression analysis
      revealed a significant association between lower V(D)/V(T) and successful
      extubation. CONCLUSIONS: A V(D)/V(T) < or =0.50 reliably predicts successful
      extubation, whereas a V(D)/V(T) >0.65 identifies patients at risk for respiratory
      failure following extubation. There appears to be an intermediate V(D)/V(T) range
      (0.51-0.65) that is less predictive of successful extubation. Routine V(D)/V(T)
      monitoring of pediatric patients may permit earlier extubation and reduce
      unexpected extubation failures.

PMID- 10890661
TI  - Bedside placement of transpyloric feeding tubes in the pediatric intensive care
      unit using gastric insufflation.
AB  - OBJECTIVE: To test the effectiveness of gastric insufflation as an adjunct to
      placement of feeding tubes in the small bowel. DESIGN: Prospective, randomized,
      controlled study. SETTING: Pediatric intensive care unit in a tertiary children's
      hospital. PATIENTS: A total of 50 children requiring enteral nutrition via a
      nasoenteral feeding tube in the small bowel. INTERVENTIONS: An unweighted
      nasoenteral feeding tube attached to a three-way stopcock and a 60 mL syringe was
      inserted through the nares into the stomach. After 10 mL/kg of air was injected,
      the tube was advanced a distance estimated to position the tip of the tube
      proximal to the pylorus. An additional 10 mL/kg of air was then injected, and the
      tube was advanced a distance needed to place the tube in the fourth part of the
      duodenum. In the control group, feeding tubes were inserted through the nares and
      into the stomach. The tube was then advanced a distance estimated to place the
      tube in the fourth part of the duodenum. No air was injected in the control
      group. MEASUREMENTS AND MAIN RESULTS: When gastric insufflation was used, 23 of
      25 feeding tubes were successfully placed in the small bowel on the first attempt
      compared with 11 of 25 in the control group (p = .001). All feeding tubes were
      successfully placed after two attempts in the gastric insufflation group compared
      with 18 of 25 in the control group (p < .001). The time between the first attempt
      at placement of a transpyloric feeding tube and the initiation of feeding was
      significantly shorter in the study group than in the control group. There were no
      complications in either group. CONCLUSION: Gastric insufflation allows rapid
      placement of feeding tubes into the small bowel with fewer attempts compared with
      a standard insertion technique in children.

PMID- 10890662
TI  - Use of transesophageal Doppler ultrasonography in ventilated pediatric patients:
      derivation of cardiac output.
AB  - OBJECTIVE: To ascertain if cardiac output (CO) could be derived from blood flow
      velocity measured in the descending aorta of ventilated children by
      transesophageal Doppler ultrasonography (TED) without the need for direct aortic
      cross sectional area measurement, and to evaluate the ability of TED to follow
      changes in CO when compared with femoral artery thermodilution. DESIGN:
      Prospective, comparison study. SETTING: A 16-bed pediatric intensive care unit of
      a university hospital. PATIENTS: A total of 100 ventilated infants and children
      aged 4 days to 18 yrs (median age, 27 months). Diagnoses included postcardiac
      surgery (n = 58), sepsis/multiple organ failure (n = 32), respiratory disease (n
      = 5), and other (n = 5). A total of 55 patients were receiving inotropes or
      vasodilators. INTERVENTIONS: When patients were hemodynamically stable, a TED
      probe was placed into the distal esophagus to obtain optimal signal, and minute
      distance (MD) was recorded. Five consecutive MD measurements were made
      concurrently with five femoral artery thermodilution measurements, and the
      concurrent measurements were averaged. CO was then manipulated by fluid
      administration or inotrope adjustment, and the readings were repeated.
      MEASUREMENTS AND MAIN RESULTS: Femoral artery thermodilution CO ranged from 0.32
      to 9.19 L/min, (median, 2.46 L/min), and encompassed a wide range of high and low
      flow states. Theoretical consideration revealed the optimal TED estimate for CO
      to be (MD x patient height2 x 10(-7)). Linear regression analysis yielded a power
      function model such that: estimated CO = 1.158 x (MD x height2 x 10(-7))(0.785),
      r2 = 0.879, standard error of the estimate = 0.266. Inclusion of a correction
      factor for potential changes in aortic cross-sectional area with hypo- and
      hypertension did not appreciably improve the predictive value of the model. MD
      was able to follow percentage changes in CO, giving a mean bias of 0.87% (95%
      confidence interval -0.85% to 2.59%), and limits of agreement of +/- 16.82%. The
      median coefficient of variation for MD was 3.3%. CONCLUSIONS: TED provides a
      clinically accurate estimate of CO across the entire pediatric age range and is
      able to follow changes in CO.

PMID- 10890663
TI  - Linear and nonlinear analysis of hemodynamic signals during sepsis and septic
      shock.
AB  - OBJECTIVE: Neuroautonomic modulation of heart rate (HR) and blood pressure were
      assessed in sepsis or septic shock. We hypothesized that these metrics would be
      diminished in pediatric patients with sepsis and septic shock, indicating
      uncoupling of the autonomic and cardiovascular systems. DESIGN: Prospective case
      series. SETTING: Pediatric intensive care unit in a tertiary care children's
      hospital. PATIENTS: Thirty pediatric patients with sepsis or septic shock.
      INTERVENTIONS: None. MEASURES AND MAIN RESULTS: Metrics used included power
      spectral analysis, a linear frequency domain measure, and detrended fluctuation
      analysis, a nonlinear technique that assesses the degree of long-range
      correlation in HR or blood pressure. We found decreased low-frequency (2.68 +/-
      0.24 vs. 3.37 +/- 0.17 [SEM] bpm2; p = .03) and high-frequency HR power (2.18 +/-
      0.14 vs. 2.79 +/- 0.23 bpm2; p = .04) and increased detrended fluctuation
      analysis scaling exponent (1.22 +/- 0.06 vs. 1.00 +/- 0.07 bpm2; p = .02) in
      sepsis vs. shock patients, respectively. Compared with sepsis or shock, recovery
      was associated with increases in low-frequency (3.61 +/- 0.15 vs. 3.05 +/- 0.19
      bpm2; p < .0001) and high-frequency HR power (3.11 +/- 0.15 vs. 2.50 +/- 0.22
      bpm2; p < .0001). CONCLUSIONS: We conclude that uncoupling of the autonomic and
      cardiovascular systems occurs over both short- and long-range time scales during
      sepsis, and the degree of uncoupling may help differentiate between sepsis,
      septic shock, and recovery states.

PMID- 10890664
TI  - Prospective study of airway management of children requiring endotracheal
      intubation before admission to a pediatric intensive care unit.
AB  - OBJECTIVE: To prospectively identify complications related to airway management
      in children before pediatric intensive care unit (ICU) admission. DESIGN: A
      descriptive, prospective study covering an 18-month period. A survey was
      completed at the time of admission to obtain demographic data, reason for
      endotracheal (ET) intubation, medications administered, location of and personnel
      responsible for ET intubation, and major/minor variances associated with airway
      management. Major variances were defined as technical problems resulting in a
      significant risk for airway trauma and increased morbidity. Minor variances were
      problems that should be avoided, but which do not significantly increase the
      immediate risk to the patient. Additional information obtained included whether a
      chest radiograph (CXR) was obtained and if postextubation problems occurred, such
      as stridor requiring treatment or reintubation. SETTING: Community hospitals,
      emergency rooms, children's hospital emergency rooms PATIENTS: All children < or
      =18 yrs of age receiving ET intubation before admission to the pediatric ICU,
      except those in cardiovascular arrest. MEASUREMENTS AND MAIN RESULTS: Data were
      collected on 250 consecutive patients. Major or minor variances were noted in 135
      (54%) patients and in 66% of patients < or =1 yr of age (p = .02865; odds ratio,
      2.0). Twenty-six percent of patients < or =1 yr of age received an
      anticholinergic agent before ET intubation compared with 40% of older patients (p
      = .04343; odds ratio, 0.504). Eleven patients received a neuromuscular blocking
      agent (NMBA) without a sedative/analgesic agent. Major variances occurred in 54%
      of patients who did not receive a NMBA and in 27% of patients who received a NMBA
      (p = .00002; odds ratio, 0.307). Forty-one patients (16%) were intubated with an
      inappropriately sized ET tube. Postintubation CXRs were obtained in 65% of
      patients managed outside of a children's hospital and in 93% of patients in a
      children's hospital emergency room (p < .00001; odds ratio, 7.199). Variances
      detectable by CXR went unrecognized in 40% of patients, despite obtaining a CXR.
      CONCLUSIONS: Emergency airway management in children can be fraught with
      problems. Most variances could be avoided by improved education regarding
      appropriate ET tube size, appropriate medication use, and improved training for
      evaluation of ET tube placement.

PMID- 10890665
TI  - Postnatal changes of extracellular volume, atrial natriuretic factor, and
      diuresis in a randomized controlled trial of high-frequency oscillatory
      ventilation versus intermittent positive-pressure ventilation in premature
      infants <30 weeks gestation.
AB  - OBJECTIVES: High-frequency oscillatory ventilation (HFOV) with a high lung volume
      strategy is an experimental mode of ventilating preterm infants aimed at
      achieving maximal alveolar recruitment Higher mean airway pressures are used
      during HFOV than during intermittent positive-pressure ventilation (IPPV), and
      the intrathoracic volume increase is relatively constant. Both factors increase
      the risk to depress organ blood flow and diuresis. Our objective was to test the
      hypothesis that high lung volume HFOV attenuates the postnatal reduction of
      extracellular volume in preterm infants by reducing plasma atrial natriuretic
      factor and diuresis. DESIGN: Prospective, randomized, controlled clinical trial.
      SETTING: University hospital, Level III neonatal intensive care unit. PATIENTS:
      Premature infants <30 wks gestation requiring intubation for respiratory distress
      syndrome within the first 6 hrs of life; 15 infants (gestational age, 26 [24-29]
      wks, birth weight 814 [452-1340] g) were randomized to HFOV, 19 infants
      (gestational age 27 [24-39] wks, birth weight 930 [644-1490] g) to IPPV.
      INTERVENTIONS: The randomized mode of ventilation was assigned within 1 hr after
      intubation. During HFOV mean airway pressure was increased as long as oxygenation
      improved and no lung overinflation was seen on chest radiograph. IPPV rates were
      > or =60/min. MEASUREMENTS AND MAIN RESULTS: We measured extracellular volume
      (sucrose dilution) and atrial natriuretic factor on Day 1 and Day 3. Mean airway
      pressure, body weight, diuresis, and fluid intake were measured daily. During
      HFOV mean airway pressure was higher at 12 hrs (median 7 cm H2O vs. 4 cm H2O; p =
      .001) and 24 hrs (median 6 cm H2O vs. 3 cm H2O; p = .01). In both groups,
      extracellular volume decreased between Day 1 and Day 3 (HFOV from 428 +/- 126 mL
      to 344 +/- 145 mL [p = .003], IPPV from 466 +/- 108 mL to 414 +/- 124 mL [p =
      .01]) and diuresis increased (HFOV, from 2.5 +/- 1.7 to 4.6 +/- 0.9 mL/kg/hr [p =
      .001]; IPPV, from 2.8 +/- 1.6 to 4.2 +/- 1.0 mL/kg/hr [p = .01]). Plasma atrial
      natriuretic factor was not decreased in the HFOV group. CONCLUSIONS: High lung
      volume HFOV as primary mode of ventilation in preterm infants <30 wks gestation
      did not result in unwanted fluid retention and a decrease in diuresis in the
      first days of life.

PMID- 10890666
TI  - Risk assessment and standardized nosocomial infection rate in critically ill
      children.
AB  - OBJECTIVES: To develop and validate a pediatric nosocomial infection risk (PNIR)
      assessment model, and to compare the daily trends in risk factors between
      patients with nosocomial infection (cases) and without nosocomial infection
      (controls) in the pediatric intensive care unit (ICU). DESIGN: Prospective
      cohort. SETTING: A 16-bed pediatric ICU in an urban, university-affiliated,
      multidisciplinary, regional referral center. PATIENTS: Patients available for
      study included consecutive admissions to the unit between May 1, 1992, and April
      30, 1993, and between May 9, 1995, and December 11, 1995. Patients from both data
      collection periods were pooled and randomly divided into training (70%) and
      validation (30%) samples. MEASUREMENTS AND MAIN RESULTS: In the logistic
      regression analysis using admission day data, three factors were shown to remain
      as independent risk factors. Invasive device use, parenteral nutrition, and the
      interaction between severity of illness-modified Pediatric Risk of Mortality III
      24 score and postoperative care were associated with 2, 6, and 1.5 times the risk
      of developing nosocomial infection, respectively. This PNIR model performed well
      in both the training and validation samples as indicated by the goodness-of-fit
      test, which evaluated standardized nosocomial infection rates (observed vs.
      predicted nosocomial infection rates). The internal validity of the PNIR model
      was good. In trend analysis, severity of illness and invasive device use appear
      to have similar trend patterns, during the first week of pediatric ICU stay.
      There was no difference in any of these risk factors between cases and controls
      after 7 days of pediatric ICU stay. CONCLUSIONS: The PNIR assessment model
      incorporates intrinsic factors, such as patient severity of illness, and
      extrinsic factors contributing to the development of nosocomial infection in this
      high-risk population. The methodology using intrinsic and extrinsic factors to
      adjust for nosocomial infections should be taken into consideration when
      evaluating interhospital comparison of nosocomial infection rates, quality
      assessment, intervention strategies, and use of treatment modalities.

PMID- 10890667
TI  - Variability in systemic arterial pressure during closed- and open-bridge
      extracorporeal life support: an in vitro evaluation.
AB  - OBJECTIVE: To compare fluctuations in systemic arterial pressure (SAP) resulting
      from changes in systemic vascular resistance (SVR) during closed- and open-bridge
      extracorporeal life support (ECLS). DESIGN: In vitro laboratory study. SETTING:
      Physiology laboratory of a tertiary care pediatric hospital. METHODS: A standard
      neonatal ECLS circuit with simulated SAP was established using normal saline as
      circulating fluid. Our reference setting included an extracorporeal flow rate of
      300 mL/min, a simulated SAP of 60 mm Hg, and a postoxygenator pressure of 150 mm
      Hg. The simulated SVR was modified by changing the degree of occlusion of the
      arterial catheter distal to the bridge. For this purpose, we used a graduated
      clamping device. Subsequently, the pressure changes were measured at four ports
      in the circuit. They were located as follows: a) on the venous tubing of the
      circuit between the bridge and the reservoir; b) on the arterial tubing of the
      circuit between the heat exchanger and the bridge; c) between the first and the
      second resistance clamps on the arterial tubing of the circuit for monitoring the
      simulated systemic arterial pressure; and d) at the reservoir. The experiment was
      repeated with various extracorporeal flow rates to the reservoir (100-300 mL/min)
      and through the bridge (100-300 mL/min using a custom-made clamp). Variations in
      the simulated SAP created by varying degrees of occlusion and flow rates were
      compared with repeated measures analysis of variance followed by the Tukey-Kramer
      test. MEASUREMENTS AND MAIN RESULTS: The open-bridge ECLS significantly reduced
      the variations in the simulated SAP by 15% to 45% (p < .001) compared with the
      closed-bridge. During closed-bridge ECLS, flashing of the bridge resulted in a
      decrease in the SAP and transient reversal of flows through the arterial and
      venous cannulae. CONCLUSIONS: Open-bridge ECLS decreases the fluctuations in the
      SAP that occur because of changes in the SVR. Open-bridge ECLS prevents transient
      iatrogenic changes in blood flow and blood pressure, caused by flashing of the
      bridge. Other potential advantages and disadvantages of the open-bridge ECLS are
      discussed. The application of prolonged open-bridge ECLS to the patients needs to
      be evaluated in animal models.

PMID- 10890668
TI  - Multiple site analytical evaluation of a portable blood gas/electrolyte analyzer
      for point of care testing.
AB  - OBJECTIVE: To evaluate the analytical performance of the SenDx 100 portable blood
      gas and electrolyte analyzer (SenDx Medical, Carlsbad, CA). DESIGN: Accuracy was
      evaluated by correlation of whole blood patient samples with the Nova Stat
      Profile 5 (Nova Biomedical, Waltham, MA) and the Ciba Corning 865 (Chiron
      Diagnostics, Medford, MA). Precision was evaluated using quality control
      materials (RNA Medical, Acton, MA). SETTING: Critical care laboratories and
      operating rooms in two institutions. MEASUREMENTS AND MAIN RESULTS: Precision
      studies performed at three different concentration levels for each analyte
      demonstrated intra-assay precision of < or =2.5% coefficient of variation and
      interassay precision of < or =4.0% coefficient of variation in all cases.
      Analysis of patient specimens in general showed good to excellent correlation to
      reference analyzers. Regression variables are tabulated. CONCLUSIONS: The SenDx
      100 portable blood gas and electrolyte analyzer is a simple and easy to use
      analyzer demonstrating acceptable performance compared with reference methods.

PMID- 10890669
TI  - Albuterol delivery by metered-dose inhaler in a pediatric high-frequency
      oscillatory ventilation model.
AB  - OBJECTIVES: To assess albuterol delivery by metered-dose inhaler (MDI) in a
      pediatric lung model ventilated by high-frequency oscillatory ventilation (HFOV).
      The percentage albuterol dose lost in the circuit's expiratory limb and the
      effects of operating frequency, inspiratory time, and use of a spacer were also
      determined. DESIGN: Prospective in vitro laboratory study. SETTING: Research
      laboratory. INTERVENTIONS: A model consisting of a HFOV and circuit, 4.5-mm
      endotracheal tube, and lung simulator was assembled. Ventilator settings were the
      following: humidified FIO2 of 1.0; mean airway pressure of 28 cm H2O; operating
      frequency of 10 Hz; pressure amplitude of 55 cm H2O; bias gas flow to maintain
      mean airway pressure; 30% inspiratory time; and temperature of 35 degrees C (95
      degrees F). Lung simulator compliance and resistance values were consistent with
      pediatric patients with pulmonary disease. A total of ten MDI canisters were used
      to administer 2000 microg of albuterol with a spacer. Circuit filters placed
      proximal to the lung simulator and in the circuit's expiratory limb collected
      albuterol exiting the endotracheal tube and any albuterol lost, respectively.
      Filters were rinsed with water and albuterol concentrations determined by high
      performance liquid chromatography. Albuterol administration was repeated at
      operating frequencies of 5 and 15 Hz, inspiratory times of 40% and 50%, and with
      an actuator instead of a spacer. Each test condition was repeated ten times.
      Analysis of variance or Student's t-test was used to determine significant
      differences in albuterol delivered or lost among the operating frequencies and
      inspiratory times, and between the spacer and actuator. MEASUREMENTS AND MAIN
      RESULTS: Albuterol delivery to the lung simulator was <1% of the administered
      dose regardless of the operating frequency, inspiratory time, or use of a spacer
      or actuator. Albuterol lost in the expiratory limb ranged from 3.28% to 14.89% of
      the administered dose. CONCLUSIONS: These in vitro results suggest albuterol
      delivery by MDI in a pediatric model of HFOV is negligible, regardless of the
      operating frequency, inspiratory time, or use of a spacer or actuator.

PMID- 10890670
TI  - What's in a day? Determining intensive care unit length of stay.
AB  - OBJECTIVE: Intensive care unit (ICU) length of stay (LOS) and hospital LOS are
      common indices used to compare performance of hospitals and are yardsticks used
      in efforts to contain costs, yet there is no standardized method of quantitating
      this outcome variable. Attempts have been made to correct LOS according to
      disease severity. The aim of this study was to quantify and compare ICU LOS using
      four commonly used methods and to determine the relationship between severity of
      illness at admission as determined by the Acute Physiology and Chronic Health
      Evaluation (APACHE) II and APACHE III scoring systems and LOS. DESIGN:
      Prospective, cohort study. SETTING: Medical and surgical ICUs of a community
      teaching hospital. MEASUREMENTS AND MAIN RESULTS: The demographic and clinical
      data of all patients admitted to the medical ICU and the surgical ICU during a 6
      month period were recorded and stored in a computerized database. Coronary care
      unit boarders and cardiothoracic patients were excluded from analysis. The date
      and exact time of all admissions and discharges were abstracted from the
      patients' flowcharts and nurses' notes. The ICU LOS of all patients was
      calculated using four common methods: a) number of calendar days (LOS-calendar);
      b) midnight bed-occupancy days (LOS-midnight); c) exact LOS calculated in hours
      divided by 24 (LOS-exact); and d) the method described by Pollack and Ruttimann
      (LOS-Pollack). There were 1,004 admissions during the study period; of these, 254
      were excluded from analysis (65 coronary care unit boarders and 189
      cardiothoracic patients). Of the remaining 750 admissions, 391 were medical ICU
      patients and 359 were surgical ICU patients. Mean age was 64 +/- 18 yrs, with 420
      (56%) male patients. The LOS-calendar differed significantly from the other three
      methods (p = .001). The LOS-midnight most closely approximated the LOS-exact. The
      mean (+/- SD) LOS-exact for the entire cohort of patients was 2.8 +/- 3.9 days,
      with a geometric mean of 1.6 days and a median of 1.4 days. An analysis of the
      data distribution showed many outliers with the plot markedly skewed to the
      right. Log transformation of the LOS-exact revealed a normal distribution. The
      APACHE II and APACHE III scores were significantly higher and the LOS-exact was
      nonsignificantly higher in the nonsurvivors. There was a poor correlation among
      the LOS-exact, log LOS-exact, LOS-exact of survivors, and LOS-exact below upper
      95th percentile with the APACHE II and APACHE III scores. CONCLUSION: We suggest
      that the LOS-midnight be used to record LOS when a hospital/ICU information
      system is unable to calculate the exact LOS in hours. Furthermore, because the
      LOS distribution is highly skewed, the geometric mean and median should be
      reported. Although APACHE II and APACHE III scores are predictive of group
      outcomes, they should not be used to predict or adjust for LOS.

PMID- 10890671
TI  - Noninvasive positive pressure ventilation in the setting of severe, acute
      exacerbations of chronic obstructive pulmonary disease: more effective and less
      expensive.
AB  - OBJECTIVE: The use of noninvasive ventilation for patients with acute respiratory
      failure has become increasingly popular over the last decade. Although the
      literature provides good evidence for the effectiveness of noninvasive
      ventilation in addition to standard therapy compared with standard therapy alone
      in patients with chronic obstructive pulmonary disease (avoiding intubation and
      improving hospital mortality), the associated costs have not been rigorously
      measured. Adding noninvasive positive pressure ventilation (NPPV) to standard
      therapy in the setting of a severe, acute exacerbation of chronic obstructive
      pulmonary disease (COPD) in patients with respiratory acidosis who are at high
      risk of requiring endotracheal intubation is both more effective and less
      expensive. DESIGN: Economic evaluation based on theoretical model. SETTING: This
      analysis base case was modeled for a tertiary care, teaching hospital. PATIENTS
      OR OTHER PARTICIPANTS: Carefully selected patients with severe exacerbations of
      COPD. INTERVENTION: The two alternative therapies compared were standard therapy
      (oxygen, bronchodilators, steroids, and antibiotics) and standard therapy plus
      NPPV. MEASUREMENTS AND MAIN RESULTS: As the hypothesis was dominance, the main
      outcomes modeled and calculated were costs, mortality rate, and rates of
      intubation between the two interventions. To determine clinical effectiveness, we
      used a meta-analysis of randomized trials evaluating the impact of NPPV on
      hospital survival. A decision tree was constructed and probabilities were applied
      at each chance node using research evidence and a comprehensive regional
      database. To provide data for this economic evaluation, MEDLINE literature
      searches were conducted. Bibliographies of relevant articles were reviewed, as
      were personal files. To estimate the costs of the alternative therapeutic
      approaches, eight types of hospitalization days were costed using the London
      Health Sciences Center costing data. Sensitivity analyses were performed, varying
      all assumptions made. The meta-analysis yielded an odds ratio for hospital
      mortality in the NPPV arm, compared with standard therapy, of 0.22 (95%
      confidence interval, 0.10-0.66). By using baseline case assumptions, we found a
      cost savings of $3,244 (1996, Canadian), per patient admission, if NPPV were
      adopted in favor of standard therapy. These findings present a scenario of clear
      dominance for treatment with NPPV. Sensitivity analyses did not alter the results
      appreciably. CONCLUSIONS: We conclude that from a hospital's perspective, NPPV
      and standard therapy for carefully selected patients with acute, severe
      exacerbations of COPD are more effective and less expensive than standard therapy
      alone.

PMID- 10890672
TI  - Plasma dehydroepiandrosterone levels during experimental endotoxemia and anti
      inflammatory therapy in humans.
AB  - OBJECTIVE: To measure the effect of experimental endotoxemia and anti
      inflammatory therapy on plasma dehydroepiandrosterone (DHEA) levels in humans.
      DESIGN: Controlled, randomized, single-blind, prospective clinical study.
      SETTING: Monitored unit in research hospital. SUBJECTS: Twelve healthy volunteers
      served as their own controls and were randomized to receive intravenous endotoxin
      (Escherichia coli) or saline separated by 1 wk. Six were randomized to receive
      ibuprofen, a cyclooxygenase inhibitor, and six were given placebo. INTERVENTIONS:
      Measurement of vital signs and hormones during a 24-hr period. MEASUREMENTS AND
      MAIN RESULTS: All subjects given endotoxin had a significant increase in plasma
      DHEA, cortisol, and adrenocorticotropic hormone (ACTH) levels (all p = .02). DHEA
      levels were maximum at 2 hrs and returned to baseline values by 6 hrs. Ibuprofen
      administration significantly blunted the endotoxin-induced increase in DHEA
      secretion (p = .001), whereas the increase in cortisol and ACTH was not affected.
      CONCLUSIONS: Acute endotoxemia leads to a rise in plasma DHEA levels in humans.
      Maximum levels of DHEA but not cortisol or ACTH were blunted by ibuprofen,
      suggesting a different regulation of these synthetic pathways in the adrenal
      cortex inner zone during acute inflammation.

PMID- 10890673
TI  - Plastic bronchitis occurring late after the Fontan procedure: treatment with
      aerosolized urokinase.
AB  - OBJECTIVE: To describe the use of aerosolized urokinase in a patient with plastic
      bronchitis after a Fontan procedure. DESIGN: Case report. SETTING: Pediatric
      intensive care unit in a university-affiliated children's hospital. PATIENTS:
      Report of one patient with acute respiratory failure secondary to plastic
      bronchitis. INTERVENTIONS: Aerosolized urokinase, multiple bronchoscopies,
      corticosteroids, mucolytics, bronchodilators, and atrial pacing. MEASUREMENTS AND
      MAIN RESULTS: Airway obstruction secondary to recurring casts improved with the
      treatments. Histologic analysis of the casts demonstrated less fibrin after
      treatments with aerosolized urokinase. No adverse events were noted. CONCLUSIONS:
      The addition of aerosolized urokinase to this patient's treatment regimen helped
      to resolve life-threatening airway obstruction secondary to fibrin casts.

PMID- 10890674
TI  - Effects of methamphetamine on trauma patients: a cause of severe metabolic
      acidosis?
AB  - OBJECTIVE: Presentation of a trauma patient with severe unexplained metabolic
      acidosis, possibly attributable to the vasoconstrictive properties of smokable
      "crystal" methamphetamine. In addition, a review of trauma registry data was
      undertaken to determine the effects of methamphetamine on trauma patients.
      DESIGN: Case report and retrospective case-control study. SETTING: Urban tertiary
      teaching hospital. PATIENTS: Two controls were obtained for each case controlling
      for age, Injury Severity Score, and mechanism of injury. Patients > or =16 yrs of
      age with a urine toxicology screen positive for methamphetamine were included.
      MEASUREMENTS AND MAIN RESULTS: Data were obtained from the trauma registry for
      the period of January 1994 to June 1995. Trauma patients using methamphetamine
      had a significantly lower blood alcohol level compared with the control group.
      Otherwise, there were no significant differences detected in vital signs,
      laboratory values, procedures, treatment, or outcome between the two groups.
      Details regarding one patient who presented with severe life-threatening acidosis
      are presented. CONCLUSIONS: Trauma patients with recent use of smokable
      methamphetamine may present with severe acidosis requiring urgent attention and
      treatment. This acidosis may exaggerate the severity of the actual injury.
      However, urine testing for methamphetamine does not identify patients who may
      harbor this acidosis.

PMID- 10890675
TI  - Pyridoxine therapy in a patient with severe hydrazine sulfate toxicity.
AB  - OBJECTIVE: To report hydrazine sulfate as a cause of severe encephalopathy and to
      report its response to high-dose pyridoxine therapy. DESIGN: Case report.
      SETTING: An adult six-bed medical/surgical intensive care unit of a general
      hospital. PATIENT: One patient who developed severe encephalopathy after
      hydrazine sulfate. INTERVENTION: 5 g i.v. pyridoxine. MEASUREMENTS AND MAIN
      RESULTS: After 180 mg/day for 2 wks followed by 360 mg/day of hydrazine sulfate
      ingestion, our patient suffered severe encephalopathy. He received mechanical
      ventilation with attendant supportive measures and high-dose pyridoxine. The
      patient's encephalopathy resolved 24 hrs after receiving pyridoxine. CONCLUSION:
      Severe encephalopathy could result from hydrazine sulfate toxicity. High-dose
      pyridoxine is an effective treatment to reverse this encephalopathy.

PMID- 10890676
TI  - Lethal late onset cblB methylmalonic aciduria.
AB  - OBJECTIVE: To alert the physicians to the possibility of a late-onset inborn
      error of metabolism in an apparently previously healthy patient with acute
      clinical presentation. DESIGN: Case report. SETTING: Pediatric unit and general
      intensive care unit. PATIENT: An apparently previously healthy 12-yr-old female
      presented acutely with vomiting, fever, bronchopneumonia, and progressive loss of
      consciousness associated with ketoacidosis, hyperglycemia, and hyperammonemia.
      She died 3 days later with a diagnosis of insulin-dependent diabetes mellitus.
      INTERVENTIONS: Intravenous hydration, glucose and insulin, mechanical
      ventilation. MEASUREMENTS AND MAIN RESULTS: Organic acid analysis on a postmortem
      sample of aqueous humor revealed high levels of methylmalonic acid. Enzymatic
      studies on cultured fibroblasts were consistent with the diagnosis of cblB
      methylmalonic aciduria. CONCLUSIONS: The diagnosis of cblB methylmalonic aciduria
      was made in a postmortem patient who died with a misdiagnosis of insulin
      dependent diabetes mellitus. Unclear biochemical findings and positive family
      history should strongly lead to suspicion of an inborn error of metabolism in an
      apparently previously healthy critically ill patient.

PMID- 10890677
TI  - Tolerance, withdrawal, and physical dependency after long-term sedation and
      analgesia of children in the pediatric intensive care unit.
AB  - OBJECTIVE: To describe the consequences of the prolonged administration of
      sedative and analgesic agents to the pediatric intensive care unit (PICU)
      patient. The problems to be investigated include tolerance, physical dependency,
      and withdrawal. DATA SOURCES: A MEDLINE search was performed of literature
      published in the English language. Cross-reference searches were performed using
      the following terms: sedation, analgesia with PICU, children, physical
      dependency, withdrawal; tolerance with sedative, analgesics, benzodiazepines,
      opioids, inhalational anesthetic agents, nitrous oxide, ketamine, barbiturates,
      propofol, pentobarbital, phenobarbital. STUDY SELECTION: Studies dealing with the
      problems of tolerance, physical dependency, and withdrawal in children in the
      PICU population were selected. DATA EXTRACTION: All of the above-mentioned
      studies were reviewed in the current manuscript. DATA SYNTHESIS: A case by case
      review is presented, outlining the reported problems of tolerance, physical
      dependency, and withdrawal after the use of sedative/analgesic agents in the PICU
      population. This is followed up by a review of the literature discussing current
      treatment options for these problems. CONCLUSIONS: Tolerance, physical
      dependency, and withdrawal can occur after the prolonged administration of any
      agent used for sedation and analgesia in the PICU population. Important
      components in the care of such patients include careful observation to identify
      the occurrence of withdrawal signs and symptoms. Treatment options after
      prolonged administration of sedative/analgesic agents include slowly tapering the
      intravenous administration of these agents or, depending on the drug, switching
      to subcutaneous or oral administration.

PMID- 10890678
TI  - Potential risk factors for developing apoptosis during septic shock.

PMID- 10890679
TI  - What can and cannot be learned from the Pittsburgh experience.

PMID- 10890680
TI  - Many roles of nitric oxide in regulating cardiac function in sepsis.

PMID- 10890681
TI  - Abdominal compartment syndrome: a century later, isn't it time to pay attention?

PMID- 10890682
TI  - What is really important to make noninvasive ventilation work.

PMID- 10890683
TI  - Pyroglutamic acid and high anion gap: looking through the keyhole?

PMID- 10890684
TI  - Abnormal neuropsychometrics early after coronary artery bypass grafting.

PMID- 10890685
TI  - Endotracheal administration of drugs during cardiopulmonary resuscitation.

PMID- 10890686
TI  - Scoring system fatigue...and the search for a way forward.

PMID- 10890687
TI  - Visualizing false lumen perfusion using sonicated albumin microspheres in aortic
      dissection repair: a state of the art application of contrast echocardiography
      and echoaortography.

PMID- 10890688
TI  - Hidden inflammatory potential of the red blood cell.

PMID- 10890689
TI  - Blood substitutes.

PMID- 10890690
TI  - Mannitol: a therapeutic alternative in the treatment of acute hyponatremia?

PMID- 10890691
TI  - Exogenous surfactant and furosemide: is more better?

PMID- 10890692
TI  - Mechanical ventilators and respiratory centers.

PMID- 10890693
TI  - Antiperoxynitrite strategies for the experimental therapy of shock.

PMID- 10890694
TI  - Tumor necrosis factor-alpha and the development of multiple organ failure.

PMID- 10890695
TI  - Can synthetic high-octane fuel avoid an energy crisis? Support for the use of
      dopexamine.

PMID- 10890696
TI  - Interaction of oxyradicals, antioxidants, and nitric oxide during sepsis.

PMID- 10890697
TI  - Diminished oxygen extraction and hypoxia in the presence of normal delivery of
      oxygen by the microvasculature.

PMID- 10890698
TI  - Endotoxin cross tolerance: another inflammatory preconditioning stimulus?

PMID- 10890699
TI  - A new score to detect neonatal nosocomial infection: "a rule of 14".

PMID- 10890700
TI  - Continuous monitoring of cardiac output: how many assumptions are valid?

PMID- 10890701
TI  - Soundbites and snapshots: what is a day?

PMID- 10890702
TI  - Cost-effectiveness of noninvasive ventilation for acute chronic obstructive
      pulmonary disease: cashing in too quickly.

PMID- 10890703
TI  - Autonomy or efficiency? Doublethink at the end of life.

PMID- 10890704
TI  - Effect of inhaled nitric oxide on neutrophil respiratory burst.

PMID- 10890705
TI  - Is low pH the cause of brain damage?

PMID- 10890706
TI  - Midazolam and pethidine for the sedation of children undergoing gastrointestinal
      endoscopy.

PMID- 10890707
TI  - Propofol infusion in children.

PMID- 10890708
TI  - Rare events often happen infrequently: propofol complications revisited.

PMID- 10890710
TI  - Renaming BIPAP.

PMID- 10890709
TI  - Dose of intravenous infusions of terbutaline and salbutamol.

PMID- 10890711
TI  - Correcting albumin and urea before extubation.

PMID- 10890712
TI  - The rocky road of xylitol to its clinical application.

PMID- 10890714
TI  - Antigenic specificity of gingival crevicular fluid antibody to Actinobacillus
      actinomycetemcomitans.
AB  - Elevated antibody levels to periodontopathogens in GCF have been identified and
      used as support for local antibody synthesis in periodontitis. This study
      examined both cross-sectional and longitudinal GCF samples for the antigenic
      specificity of antibody in the fluid. GCF samples were collected from each tooth
      of 27 periodontitis patients infected with A. actinomycetemcomitans. Levels of
      IgG antibody in the GCF were assessed by means of an ELISA and compared with
      serum for determination of local elevations. A proportion of those GCF samples
      that exhibited significantly elevated antibody were examined by Western
      immunoblotting to outer membrane antigens from A. actinomycetemcomitans.
      Homologous sera were also examined for comparison of antibody specificities. Of
      the sites with elevated IgG antibody, 87% were colonized by A.
      actinomycetemcomitans; however, 46% of sites with A. actinomycetemcomitans
      infection did not have elevated antibody. Cross-sectional studies identified a 78
      to 100% agreement between the antibody specificities in GCF and those in serum.
      Additionally, patterns of antibody reactivity in both GCF and serum in the
      subjects were often very distinctive. Longitudinal alterations in GCF antibody
      were examined in 15 patients through a monitoring interval of up to 2 years and
      showed a general conservation of specificities. However, 7/15 patients exhibited
      a definite acquisition of different antibody specificities during the monitoring.
      These results describe a relationship between elevated local antibody and A.
      actinomycetemcomitans infection. Furthermore, the antibody specificities in serum
      appear to reflect generally the local response to this pathogen.

PMID- 10890713
TI  - Use of dental care by HIV-infected medical patients.
AB  - Although increasing attention has been paid to the use of dental care by HIV
      patients, the existing studies do not use probability samples, and no accurate
      population estimates of use can be made from this work. The intent of the present
      study was to establish accurate population estimates of the use of dental
      services by patients under medical care. The study, part of the HIV Cost and
      Services Utilization Study (HCSUS), created a representative national probability
      sample, the first of its kind, of HIV-infected adults in medical care. Both
      bivariate and logistic regressions were conducted, with use of dental care in the
      preceding 6 months as the dependent variable and demographic, social, behavioral,
      and disease characteristics as independent variables. Forty-two percent of the
      sample had seen a dental health professional in the preceding 6 months. The
      bivariate logits for use of dental care show that African-Americans, those whose
      exposure to HIV was caused by hemophilia or blood transfusions, persons with less
      education, and those who were employed were less likely to use dental care (p <
      0.05). Sixty-five percent of those with a usual source of care had used dental
      care in the preceding 6 months. Use was greatest among those obtaining dental
      care from an AIDS clinic (74%) and lowest among those without a usual source of
      dental care (12%). We conclude that, in spite of the high rate of oral disease in
      persons with HIV, many do not use dental care regularly, and that use varies by
      patient characteristics and availability of a regular source of dental care.

PMID- 10890715
TI  - Water-insoluble glucan synthesis by mutans streptococcal strains correlates with
      caries incidence in 12- to 30-month-old children.
AB  - Early mutans streptococci (MS) infection has been associated with higher caries
      activity in childhood. Since colonization with MS does not always lead to caries
      activity, additional factors may be involved in MS cariogenicity. For example, MS
      may differ in virulence traits such as the potential to synthesize glucan
      polymers from sucrose. In the present study, we tested the hypothesis that caries
      activity can be associated with variations in virulence factor expression of MS
      infecting strains. At baseline, levels of MS obtained by the tongue-blade
      sampling method, and the presence of visible plaque on upper incisors, were
      measured in 101 12- to 30-month-old children. Dental caries lesions were
      diagnosed at baseline and after one year. Caries incidence data were then used to
      select ten caries-free and nine caries-active children from whom a total of 20 MS
      fresh isolates was studied. Water-insoluble glucan (WIG) synthesis, final pH, and
      sucrose-dependent adherence on glass surfaces were measured in these MS isolates.
      Concentrated culture supernatants were separated in duplicate SDS-PAGE gels,
      which were then either stained for protein or incubated with 5% sucrose. The
      intensities of the WIG bands developed in the 5% sucrose PAGE gels and the
      corresponding protein-stained GTF bands were measured by scanning densitometry.
      High MS levels (> or = 100 CFU) were associated with high caries incidence (p <
      0.01). The presence of visible plaque did not correlate with caries incidence.
      The intensities of WIG bands were positively correlated with caries incidence (p
      < 0.05) and with the ability of MS to adhere to glass surfaces (p < 0.05).
      Analysis of our data suggests that the ability to synthesize WIG is an important
      virulence factor in initial caries development by increasing MS adherence and
      accumulation in the plaque of young children.

PMID- 10890716
TI  - Co-ordinated mandibular and head-neck movements during rhythmic jaw activities in
      man.
AB  - Recent observations in man of concomitant mandibular and head movements during
      single maximal jaw-opening/-closing tasks suggest a close functional relationship
      between the mandibular and the head-neck motor systems. This study was aimed at
      further testing of the hypothesis of a functional integration between the human
      jaw and neck regions. Spatiotemporal characteristics of mandibular and associated
      head movements were evaluated for 3 different modes of rhythmic jaw activities:
      self-paced continuous maximal jaw-opening/-closing movements, paced continuous
      maximal jaw-opening/-closing movements at 50 cycles/minute, and unilateral
      chewing. Mandibular and head-neck movements were simultaneously recorded in 12
      healthy young adults, by means of a wireless opto-electronic system for 3-D
      movement recordings, with retro-reflective markers attached to the lower
      (mandible) and upper (head) incisors. The results showed that rhythmic mandibular
      movements were paralleled by head movements. An initial change in head position
      (head extension) was seen at the start of the first jaw-movement cycle, and this
      adjusted head position was retained during the following cycles. In addition to
      this prevailing head extension, the maximal jaw-opening/-closing cycles were
      paralleled by head extension-flexion movements, and in general the start of these
      head movements preceded the start of the mandibular movements. The results
      support the idea of a functional relationship between the temporomandibular and
      the cranio-cervical neuromuscular systems. We therefore suggest a new concept for
      human jaw function, in which "functional jaw movements" are the result of
      activation of jaw as well as neck muscles, leading to simultaneous movements in
      the temporomandibular, atlanto-occipital, and cervical spine joints.

PMID- 10890717
TI  - In vivo degradation of resin-dentin bonds in humans over 1 to 3 years.
AB  - The longevity of resin restorations is currently an area of great interest in
      adhesive dentistry. However, no work has been conducted to investigate the
      durability of resin-dentin bond structures using human substrate in vivo. The
      purpose of this study was to investigate the degradation of the resin-dentin bond
      structures aged in an oral environment for 1, 2, or 3 years. Cavities were
      prepared in primary molars, and an adhesive resin system (Scotchbond Multi
      Purpose) was applied to the cavity. After 1 to 3 years, following the eruption of
      the succedaneous permanent teeth, the resin-restored teeth were extracted.
      Immediately after extraction, those teeth were sectioned perpendicular to the
      adhesive interface and trimmed to produce an hourglass-shaped specimen. Then, a
      micro-tensile test was performed at a crosshead speed of 1.0 mm/min. The mean
      bond strengths were statistically compared with one-way ANOVA and Fisher's PLSD
      test (p < 0.05). Further, all fractured surfaces were observed by SEM, and the
      area fraction of failure mode was calculated by means of a digital analyzer on
      SEM photomicrographs. There were significant differences in tensile-bond strength
      among all 3 groups (p < 0.05), with mean values ranging from 28.3 +/- 11.3 MPa
      (control), to 15.2 +/- 4.4 MPa (1 to 2 years), to 9.1 +/- 5.1 MPa (2 to 3 years).
      Moreover, under fractographic analysis, the proportion of demineralized dentin at
      the fractured surface in specimens aged in an oral environment was greater than
      that in control specimens. Furthermore, degradation of resin composite and the
      depletion of collagen fibrils was observed among the specimens aged in an oral
      environment. Analysis of the results of this study indicated that the degradation
      of resin-dentin bond structures occurs after aging in the oral cavity.

PMID- 10890718
TI  - Whisker-reinforced heat-cured dental resin composites: effects of filler level
      and heat-cure temperature and time.
AB  - Currently available dental resin composites are inadequate for use in large
      stress-bearing crown and multiple-unit restorations. The aim of this study was to
      reinforce heat-cured composites with ceramic whiskers. It was hypothesized that
      whiskers substantially strengthen heat-cured composites. It was further
      hypothesized that whisker filler level and heat-cure temperature and time
      significantly influence composite properties. Silica particles were fused onto
      the whiskers to facilitate silanization and to roughen the whiskers for improved
      retention in the matrix. The whisker filler mass fraction was varied from 0% to
      79%, the heat-cure temperature from 80 degrees C to 180 degrees C, and cure time
      from 10 min to 24 hrs. Flexural strength, work-of-fracture, and fracture
      toughness of the composites were measured, and specimen fracture surfaces were
      examined with scanning electron microscopy. Filler level had a significant effect
      on composite properties. The whisker composite with 70% filler level had a
      flexural strength in MPa (mean +/- SD; n = 6) of 248 +/- 23, significantly higher
      than 120 +/- 16 of an inlay/onlay composite control and 123 +/- 21 of a
      prosthetic composite control (Tukey's multiple comparison test; family confidence
      coefficient = 0.95). Heat-cure time also played a significant role. At 120
      degrees C, the strength of composite cured for 10 min was 178 +/- 17, lower than
      236 +/- 14 of composite cured for 3 hrs. The strength of whisker composite did
      not degrade after water-aging for 100 d. In conclusion, heat-cured composites
      were substantially reinforced with whiskers. The reinforcement mechanisms
      appeared to be whiskers bridging and resisting cracks. The strength and fracture
      toughness of whisker composite were nearly twice those of currently available
      inlay/onlay and prosthetic composites.

PMID- 10890719
TI  - Crack initiation modes in bilayered alumina/porcelain disks as a function of
      core/veneer thickness ratio and supporting substrate stiffness.
AB  - We hypothesize that the fracture resistance of alumina core/porcelain veneer
      disks increases and that crack initiation shifts from veneer to core as the
      core/veneer thickness ratio (t(C)/t(V)) increases from 0.5/1.0 to 1.3/0.2, or as
      the elastic modulus of the supporting substrate (E(S)) to which it is resin
      bonded increases from 5.1 to 226 GPa. When supported by a low-modulus substrate,
      disks with low t(C)/t(V) ratios exhibited cracks in the veneer and within the
      core, while those with high t(C)/t(V) ratios demonstrated core cracks, but not
      veneer cracks. None of the disks supported by Ni-Cr alloy (E = 226 GPa) exhibited
      core cracks. These results support the hypothesis that the crack initiation site
      shifts as the t(C)/t(V) ratio increases, but the increase in E(S) did not affect
      the crack initiation site. This study suggests that the t(C)/t(V) ratio is the
      dominant factor that controls the failure initiation site in bilayered ceramic
      disks.

PMID- 10890720
TI  - Three-dimensional analysis of root canal geometry by high-resolution computed
      tomography.
AB  - A detailed understanding of the complexity of root canal systems is imperative to
      ensure successful root canal preparation. The aim of this study was to evaluate
      the potential and accuracy of a three-dimensional, non-destructive technique for
      detailing root canal geometry by means of high-resolution tomography. The anatomy
      of root canals in 12 extracted human maxillary molars was analyzed by means of a
      micro-computed tomography scanner (microCT, cubic resolution 34 microm). A
      special mounting device facilitated repeated precise repositioning of the teeth
      in the microCT. Surface areas and volumes of each canal were calculated by
      triangulation, and means were determined. Model-independent methods were used to
      evaluate the canals' diameters and configuration. The calculated and measured
      volumes and the areas of artificial root canals, produced by the drilling of
      precision holes into dentin disks, were well-correlated. Semi-automated
      repositioning of specimens resulted in near-perfect matching (< 1 voxel) when
      outer canal contours were assessed. Root canal geometry was accurately assessed
      by this innovative technique; therefore, variables and indices presented may
      serve as a basis for further analyses of root canal anatomy in experimental
      endodontology.

PMID- 10890721
TI  - Immunolocalization and adenoviral vector-mediated manganese superoxide dismutase
      gene transfer to experimental oral tumors.
AB  - The anti-oxidant enzyme system protects cellular macromolecules against damage
      from reactive oxygen species. One component of this system, manganese superoxide
      dismutase (MnSOD), has also been shown to display tumor suppressor gene-like
      activity. The purpose of this study was to examine changes in MnSOD expression
      during hamster cheek pouch carcinogenesis, and the effects of MnSOD
      overexpression using an adenoviral vector. Tumor induction was carried out using
      7,12-dimethylbenz[alpha]anthracene. Animals were killed at periodic intervals,
      and cheek pouch tissues were excised and examined for MnSOD expression by
      immunohistochemistry and digital image analysis. We observed a reduction in MnSOD
      expression as early as 2 weeks after the start of carcinogen application. Low
      MnSOD expression persisted until the end of the 23-week experimental period.
      Solid hamster cheek pouch carcinoma xenografts were then established in nude
      mice. An adenoviral vector encoding the human MnSOD gene was delivered to the
      xenografts by direct injection. We observed high, immediate expression of MnSOD
      in the xenografts that persisted for 10 days following cessation of viral
      construct delivery. Delivery of the MnSOD construct resulted in a maximal 50%
      reduction in tumor growth compared with untreated controls. Our results suggest
      that MnSOD may be a tumor suppressor gene in the hamster cheek pouch model
      system.

PMID- 10890722
TI  - PTCH gene mutations in odontogenic keratocysts.
AB  - An odontogenic keratocyst (OKC) is a benign cystic lesion of the jaws that occurs
      sporadically or in association with nevoid basal cell carcinoma syndrome (NBCCS).
      Recently, the gene for NBCCS was cloned and shown to be the human homologue of
      the Drosophila segment polarity gene Patched (PTCH), a tumor suppressor gene. The
      PTCH gene encodes a transmembrane protein that acts in opposition to the Hedgehog
      signaling protein, controlling cell fates, patterning, and growth in numerous
      tissues, including tooth. We investigated three cases of sporadic odontogenic
      keratocysts and three other cases associated with NBCCS, looking for mutations of
      the PTCH gene. Non-radioactive single-strand conformational polymorphism and
      direct sequencing of PCR products revealed a deletion of 5 base pairs (bp) in
      exon 3 (518delAAGCG) in one sporadic cyst as well as mutations in two cysts
      associated with NBCCS, a nonsense (C2760A) and a missense (G3499A) alteration.
      This report is the first to describe a somatic mutation of PTCH in sporadic
      odontogenic keratocysts as well as two novel mutations in cysts associated with
      NBCCS, indicating a similar pathogenesis in a subset of sporadic keratocysts.

PMID- 10890723
TI  - Interleukin-1alpha-dependent regulation of matrix metalloproteinase-9(MMP-9)
      secretion and activation in the epithelial cells of odontogenic jaw cysts.
AB  - Interleukin-1alpha (IL-1alpha) and matrix metalloproteinase-9 (MMP-9) are thought
      to be involved in odontogenic cyst expansion. In this study, we investigated the
      effects of IL-1alpha on the secretion and activation of MMP-9 in odontogenic jaw
      cysts. An active form of MMP-9 was present in odontogenic keratocyst (6 of 8
      cases) fluids more frequently than dentigerous cyst (3 of 10 cases) and radicular
      cyst (3 of 10 cases) fluids, although proMMP-9 was present in all cyst fluids.
      Odontogenic keratocyst fragments in explant culture secreted a larger amount of
      IL-1alpha than dentigerous cyst and radicular cyst fragments in explant culture,
      and spontaneously secreted both proMMP-9 and an active form of MMP-9. The
      fragments of dentigerous cysts and radicular cysts secreted a small amount of
      proMMP-9, but no active form of MMP-9. Exogenously added recombinant human IL
      1alpha (rhlL-1alpha) increased the secretion and activation of proMMP-9 in the
      fragments of dentigerous cysts and radicular cysts. The epithelial cells isolated
      from odontogenic keratocysts secreted IL-1alpha and proMMP-9 without stimulation.
      Under the cultivation on a fibronectin-coated dish, rhIL-1alpha increased the
      secretion of proMMP-9 from the epithelial cells in a dose-dependent manner.
      Moreover, rhIL-1alpha induced the secretion of proMMP-3 and plasminogen activator
      urokinase (u-PA) from the epithelial cells, and converted the secreted proMMP-3
      to the active form in the presence of plasminogen. The secreted proMMP-9 was also
      activated in the presence of rhIL-1alpha and plasminogen. Hence, our results
      suggest that IL-1alpha may up-regulate not only proMMP-9 secretion but also
      proMMP-9 activation by inducing proMMP-3 and u-PA production in the cyst
      epithelial cells by autocrine/paracrine regulatory mechanisms.

PMID- 10890724
TI  - Mandibular bone formation rates in aged ovariectomized rats treated with anti
      resorptive agents alone and in combination with intermittent parathyroid hormone.
AB  - Anti-resorptive agents--including estrogen (E), calcitonin (CT), and
      bisphosphonates--are established in the treatment of osteoporosis. Intermittent
      administration of parathyroid hormone (PTH) stimulates bone formation and is a
      possible therapeutic agent for the restoration of bone mass. The purpose was to
      determine the effects of the anti-resorptive agents alone and in combination with
      intermittent PTH on bone formation in the mandible and a long bone in the aged
      ovariectomized (Ovx) rat. Female rats were ovariectomized or sham-operated. One
      year later, groups of Ovx rats were treated with E, CT, or the bisphosphonate,
      Risedronate (NE). Additional groups of Ovx rats were treated with each of these
      agents in combination with human PTH for 10 weeks. Estrogen treatment suppressed
      most indices of bone formation in the humerus and mandible, while NE decreased
      some indices of formation at the endocortical and endosteal surfaces of the
      mandible and humerus. Increased double-labeled surface and mineral apposition
      rates were observed only on the mandibular endosteal surfaces following CT
      treatment. When the anti-resorptive agents were combined with intermittent PTH,
      most indices of bone formation at all skeletal sites were substantially greater
      than those of the untreated Ovx controls as well as the E-, CT-, and NE-treated
      groups, respectively. These results provide additional evidence that established
      and emerging therapies for osteoporosis affect osseous tissues in the oral
      cavity, and this may influence the progression of diseases and/or aging changes
      at this site.

PMID- 10890725
TI  - Influence of environmental pH on the reactivity of Candida albicans with salivary
      IgA.
AB  - Salivary secretory IgA reacts with a group of heat-shock mannoproteins
      preferentially expressed on Candida albicans yeast cells and germ tubes grown at
      37 degrees C. Since other environmental factors can also modulate the expression
      of those antigens, we have investigated the influence of the pH of the culture
      medium on the expression of the antigens reacting with human salivary IgA by C.
      albicans. By indirect immunofluorescence, yeast cells grown in Sabouraud glucose
      broth at 37 degrees C showed a statistically significant increase in reactivity
      with salivary IgA (p < 0.0001) when compared with cells grown at 25 degrees C at
      the 4 pH values studied (3.3, 5.9, 7.5, and 9.5), the highest reactivity and the
      major heat-shock effect being observed at pH 5.9. The decrease in reactivity with
      salivary IgA observed in C. albicans cells grown at pH values of 3.3 and 9.5 was
      confirmed by Western blotting. Salivary IgA reacted with polydispersed materials
      from the cell walls of molecular masses > 55 kDa, which were more expressed at
      neutral pH than at acidic or alkaline pH values. A similar reactivity was
      observed when the antigenic extracts were stained with an antiserum directed
      against oligosaccharides present in antigen 6 of C. albicans serotype A. The
      differences in reactivity presented by salivary IgA may be related to a decrease
      in the expression of polysaccharides present on the surfaces of the yeast cells
      of C. albicans grown at acidic or alkaline pH values. The low reactivity of
      salivary IgA with C. albicans cells grown at acidic pH values may help to explain
      the association between acidic saliva and the carriage of Candida in the oral
      cavity, as well as with oral candidiasis.

PMID- 10890726
TI  - An examination of the practicality of the simplex procedure.
AB  - OBJECTIVE: The practical importance of the simplex procedure, a subjective
      technique used to refine the frequency gain characteristic (FGC) of a hearing aid
      according to listener preference, was determined for individual listeners by
      measuring hearing aid benefit using both laboratory studies and field studies.
      DESIGN: A digital research hearing aid with two memories was used as the test
      hearing aid. The modified simplex procedure was used to select the FGC judged to
      yield the best speech clarity in the presence of low-level vent noise and again
      in higher-level cafeteria noise by 10 experienced hearing aid users. The FGCs
      assessed by the listeners varied systematically from The National Acoustic
      Laboratories Revised (NAL-R) response in the amount of low-frequency or high
      frequency amplification. The benefit obtained with these two simplex-selected
      settings was compared with that obtained using the NAL-R FGC. Measures of benefit
      included speech recognition testing in the laboratory and ratings of speech
      intelligibility in the field. In the first field study, the two simplex settings
      were compared. In the second field study, the simplex-selected setting for higher
      level noise and the NAL-R setting were compared. RESULTS: In the laboratory, the
      majority of listeners selected an increase in the low-frequency channel gain
      compared with the NAL-R. Desired high-frequency channel gain was correlated with
      degree of hearing loss and type of background noise. The benefit as measured
      using nonsense syllables did not differ significantly among the three fittings,
      but differences in benefit were measurable with the rating procedure. Five of
      eight participants noticed a significant difference in their speech understanding
      in the real world for the FGCs selected in different background noises. Two of
      seven participants reported significantly better speech intelligibility with a
      simplex-selected FGC compared with the NAL-R FGC in the real world. The remaining
      subjects reported similar speech understanding capabilities with both hearing aid
      settings. CONCLUSIONS: The majority of subjects included in this study selected
      an FGC with real ear insertion gain different than the NAL-R prescription to
      improve subjective speech understanding in the laboratory. A small number of
      these listeners rated the selected FGC as providing improved speech
      intelligibility over the NAL-R FGC in the real world. This finding indicates that
      the simplex procedure should be used selectively to modify the NAL-R
      prescription. A screening technique would be useful in selecting those who might
      benefit from a modified fitting. The simplex procedure may also prove to be
      useful in selecting listeners who would benefit from multiple memory hearing
      aids.

PMID- 10890727
TI  - Impact of noise source configuration on directional hearing aid benefit and
      performance.
AB  - OBJECTIVE: To evaluate the impact of the position of noise source(s) and
      reverberation on the directional benefit and performance of three commercially
      available directional hearing aids. DESIGN: Directional benefit and performance
      were measured for four different configurations of competing noise source(s) in
      two different reverberant rooms. Three pairs of hearing aids representing three
      commercial models were selected based on electroacoustic evaluation of
      directivity. Directional benefit and performance of 25 subjects with symmetrical,
      sloping, sensorineural hearing loss were measured in all test environments using
      a modified version of the Hearing in Noise Test. RESULTS: Both reverberation and
      configuration of the competing noise source(s) significantly affected directional
      benefit and performance. There was no significant correlation between directional
      benefit and directional performance. The order of benefit and performance across
      hearing aid brands (from best to worst) varied depending on the noise source
      configuration. CONCLUSIONS: Data revealed increasing reverberation significantly
      decreased directional benefit and performance. The absolute and relative (rank
      ordering) directional benefit and performance varied across hearing aid brand,
      with noise source configuration. These results suggest that data collected in
      traditional test environments (e.g., a single competing noise placed at 180
      degrees azimuth) cannot be used to accurately predict directional benefit or
      performance in the majority of other test and real-world environments. The impact
      of reverberation and noise source configuration on directional
      benefit/performance can be explained fairly well by the interaction between the
      spatial properties of the noise source(s) and the polar directivity patterns of
      the hearing aids.

PMID- 10890728
TI  - High-frequency hearing loss and wideband middle ear impedance in children with
      otitis media histories.
AB  - OBJECTIVE: This study was undertaken to determine the relationship between
      extended-high-frequency (EHF) hearing losses and wideband middle ear impedance in
      children with chronic otitis media (OM) histories. DESIGN: Children with OM
      histories were selected from a prospective study cohort if they had normal
      tympanograms, no air-bone gaps, and no otoscopic evidence of active OM at the
      time of testing. OM subjects were divided into two groups, those with Better
      Hearing in the EHF range and those with Worse Hearing in the EHF range. The OM
      groups were compared with an age-matched, healthy Control group that had no more
      than five documented episodes of OM and no more than two in any 1 yr. All
      children were 9 to 16 yr of age. Subjects were tested by standard audiometric
      methods in the conventional audiometric range (0.25 to 8.0 kHz) and the EHF range
      (8 to 20 kHz). Middle ear impedance and reflectance were measured with an
      experimental system over the frequency range 0.25 to 10.08 kHz. RESULTS: The
      Worse Hearing OM group had slightly poorer hearing in the conventional
      audiometric frequency range compared with the other two groups. The Better
      Hearing OM group and the Control group had nearly identical EHF hearing. The
      Worse Hearing OM group had significantly poorer EHF hearing compared with the
      other two groups, the difference increasing exponentially with frequency. Middle
      ear impedance differences among groups were confined to low frequencies (<2 kHz).
      The Control group had significantly higher negative reactance than the two OM
      groups. There were no significant group differences in impedance or reflectance
      in the high frequencies (2 to 10 kHz). CONCLUSIONS: The results of this study
      confirm those of previous reports that children who have recovered from chronic
      OM have significantly poorer hearing in the EHF range compared with children
      without significant OM histories. The EHF hearing losses that occur in children
      with OM histories are strongly frequency dependent, suggesting a preferential
      effect on the base of the cochlea. Middle ear impedance and reflectance
      differences do not account for the EHF hearing losses observed in children with
      OM histories. The results support the hypothesis that OM-related EHF hearing
      losses are cochlear in origin.

PMID- 10890729
TI  - Otoacoustic emissions and tympanometry in children with otitis media.
AB  - OBJECTIVE: To examine otoacoustic emission and tympanometric findings in children
      with surgically confirmed middle ear effusion (MEE). DESIGN: A total of 102
      children aged 0.7 to 11.4 yr undergoing surgery because of otitis media were
      included in the study. A tympanometric examination and transient evoked
      otoacoustic emission (TEOAE) measurement were performed on each ear before
      myringotomy. MEE was aspirated, weighed and classified as mucoid or nonmucoid.
      TEOAE measurements were compared with the quantity and quality of MEE and to the
      tympanometric findings. RESULTS: Fifty (72%) ears out of the 65 ears containing
      effusion showed reduced TEOAE. The quantity of effusion was associated
      significantly (p < 0.001) with the TEOAE responses, and mucoid effusion reduced
      the emissions more than nonmucoid. The sensitivity of tympanometry in identifying
      the ears without recordable TEOAE was 73% and the specificity 81%. CONCLUSION:
      MEE results in a significant reduction in TEOAEs even when the effusion is
      nonmucoid. This suggests that transmission of acoustic energy to and from the
      middle ear is altered in children experiencing any form of otitis media with
      effusion.

PMID- 10890730
TI  - Four earplugs in search of a rating system.
AB  - OBJECTIVE: The performance of four insert earplugs was evaluated by determining
      the Noise Reduction Rating (NRR) and the Subject-Fit Noise Reduction Rating
      [NRR(SF)]. The NRR and NRR(SF) were calculated from real-ear attenuation at
      threshold (REAT) data collected using the experimenter-fit protocol described in
      the now-rescinded ANSI S3.19-1974 (American National Standards Institute, 1974)
      and the subject-fit protocol of the recently revised ANSI S12.6-1997 (American
      National Standards Institute, 1997) standards for REAT measurement. DESIGN: A
      comparison of the experimenter-fit and subject-fit REAT performance was conducted
      using four pools of subjects, one pool per protector. Each device was tested with
      at least 20 subjects, the minimum size necessary to estimate the NRR(SF) for an
      earplug. The REAT was measured with third-octave narrowband noise stimuli for
      center frequencies at 0.125, 0.25,0.5, 1, 2, 3.15, 4, 6.3, and 8 kHz. The REAT
      means and standard deviations were compared with the manufacturer data. RESULTS:
      This study showed that the NRR(SF) is typically lower than the NRR and that the
      NRR(SF) is not well-predicted by the NRR derating schemes recommended by the
      National Institute for Occupational Safety and Health and required by the
      Occupational Safety and Health Administration. CONCLUSION: The difference between
      the present NRR on hearing protector labels and the NRR(SF) is sufficiently large
      and unpredictable enough to render the application of derating schemes
      meaningless even though these schemes attempt to account for the difference
      between the laboratory and real-world outcomes. The only way to provide a
      protector noise rating that is predictive of a real-world outcome is to retest
      the protector according to the subject-fit method of ANSI S12.6-1997 (American
      National Standards Institute, 1997).

PMID- 10890731
TI  - Effects of dynamic range and amplitude mapping on phoneme recognition in Nucleus
      22 cochlear implant users.
AB  - OBJECTIVE: To determine the consequences for phoneme recognition of errors in
      setting threshold and loudness levels in cochlear implant listeners using a 4
      channel continuous interleaved sampling (CIS) speech processor. DESIGN: Three
      Nucleus-22 cochlear implant listeners, who normally used the SPEAK speech
      processing strategy participated in this study. An experimental 4-channel CIS
      speech processor was implemented in each listener as follows. Speech signals were
      band-pass filtered into four broad frequency bands and the temporal envelope of
      the signal in each band was extracted by half-wave rectification and low-pass
      filtering. A power function was used to convert the extracted acoustic amplitudes
      to electric currents. The electric currents were dependent on the exponent of the
      mapping power function and the electrode dynamic range, which was determined by
      the minimum and maximum stimulation levels. In the baseline condition, the
      minimum and maximum stimulation levels were defined as the psychophysically
      measured threshold level (T-level) and maximum comfortable level (C-level). In
      the experimental conditions, the maximum stimulation levels were fixed at the C
      level and the dynamic range (in dB) was changed by varying the minimum
      stimulation levels on all electrodes. This manipulation simulates the effect of
      an erroneous measurement of the T-level. Phoneme recognition was obtained as the
      dynamic range of electrodes was changed from 1 dB to 20 dB and as the exponent of
      the power-law amplitude mapping function was changed from 0.1 to 0.4. RESULTS:
      For each mapping condition, the electric dynamic range had a significant, but
      weak effect on vowel and consonant recognition. For a strong compression (p =
      0.1), best vowel and consonant scores were obtained with a large dynamic range
      (12 dB). When the exponent of the mapping function was changed to 0.2 and 0.4,
      the dynamic range producing the highest scores decreased to 6 dB and 3 dB,
      respectively. CONCLUSIONS: Phoneme recognition with a 4-channel CIS strategy was
      only mildly affected by large changes in both electric threshold and loudness
      mapping. Errors in threshold by a factor of 2 (6 dB) and in the loudness mapping
      exponent by a factor of 2 were required to produce a significant decrease in
      performance. In these extreme conditions, the effect of the electric dynamic
      range on phoneme recognition could be due to two independent factors: abnormal
      loudness growth and a reduction in the number of discriminable intensity steps.
      The decrease in performance caused by a reduced electric dynamic range can be
      compensated by a more expansive power-law mapping function, as long as the number
      of discriminable intensity steps is moderately large (e.g., >8).

PMID- 10890732
TI  - The prognostic value of promontory electric auditory brain stem response in
      pediatric cochlear implantation.
AB  - OBJECTIVE: To test the hypothesis that children with clear promontory
      electrically evoked auditory brain stem responses (prom-EABRs) would outperform,
      after cochlear implantation, children who had no prom-EABR preoperatively.
      DESIGN: A prospective study was undertaken on 47 implanted children assigning
      them to two groups (group A: 35 children with a clear wave e-V in the
      preoperative prom-EABR and group B: 12 children with no prom-EABR). Speech
      perception and speech intelligibility were assessed annually up to 3 yr after
      implantation with the IOWA sentence test (level A and level B), Connected
      Discourse Tracking, Categories of Auditory Performance, and Speech
      Intelligibility Rating. t-test and Mann-Whitney U test were used to compare the
      above outcome measures in the two groups. RESULTS: There was no statistically
      significant difference between the two groups on any of the outcome measures at
      any interval. Moreover, the small differences observed showed no consistent trend
      toward either group of children. Further analysis revealed that the outcomes have
      not been affected by possible confounding factors (age at implantation, duration
      of deafness, preoperative unaided pure-tone thresholds, and number of inserted
      electrodes). CONCLUSIONS: The results suggest that children with no prom-EABR
      performed at levels comparable with children who had clear promontory responses
      preoperatively. The prognostic value of prom-EABR is limited and absence of a
      prom-EABR is not, by itself, a contraindication for cochlear implantation.
      However, in selected cases (congenital malformations, cochlear nerve dysplasia or
      suspected aplasia, narrow internal auditory canal, etc.) the presence of a prom
      EABR is a positive finding in the assessment of candidates for cochlear
      implantation as it confirms the existence of intact auditory neurones.

PMID- 10890733
TI  - Maturation of mismatch negativity in school-age children.
AB  - OBJECTIVE: Event-related potentials were recorded to investigate the maturation
      of auditory processing in school-age children. DESIGN: The mismatch negativity
      (MMN) was obtained in an oddball tone discrimination paradigm in 66 school-age
      children and 12 adults. In the children's data, a prominent negativity to both
      the standard and deviant tone, peaking around 200 msec, was observed, and
      compared with the N1 auditory evoked potential component. RESULTS: The MMN was
      found to decrease with latency by 11 msec/yr from 4 to 10 yr of age. No
      developmental change in MMN amplitude was seen from 4 to 10 yr of age. However,
      the MMN amplitude was significantly smaller in adults than in children. The
      prominent negativity in children was significantly later than the adult N1
      component, and did not change in latency from 4 to 10 yr of age. This finding
      adds to a body of evidence suggesting that this prominent negativity and the
      adult N1 are not the same component. The magnitude of the prominent negativity in
      children decreased slightly with age. CONCLUSION: Changes in the timing of the
      brain discriminative response, MMN, suggest systematic maturational changes in
      auditory processing.

PMID- 10890734
TI  - Intracranial evidence for differential encoding of frequency and duration
      discrimination responses.
AB  - OBJECTIVE: To identify cortical areas involved in auditory detection and
      discrimination of frequency and duration stimuli in an awake child. DESIGN:
      Single case study recording intracranial auditory event-related potentials to
      auditory odd-ball stimuli varying in duration and/or frequency. RESULTS: N1 wave
      to detection was recorded maximally just above the Sylvian fissure 1 cm posterior
      to the mismatch negativity (MMN) response to discrimination. Frequency MMN
      overlapped with the N1 whereas duration MMN appeared 100 msec later. MMN to both
      duration and frequency appeared as an additive bifid response. CONCLUSIONS: It is
      suggested that feature-specific neuronal networks are activated after changes in
      sounds, which may underpin a fast parallel preattentive process (MMN).

PMID- 10890735
TI  - Auditory brain stem response in small acoustic neuromas.
AB  - OBJECTIVE: The auditory brain stem response (ABR) has been criticized recently as
      an insensitive measure for the detection of small acoustic neuroma (AN). This
      study was undertaken to evaluate our experience with the efficacy of ABR in
      detection of small tumors. STUDY DESIGN: Retrospective case review. Twenty-five
      patients with surgically proven small ANs measuring 1 cm or less were reviewed.
      In addition, 568 patients who underwent screening ABR were reviewed to evaluate
      the rate of false positive results at our institution. RESULTS: ABR was abnormal
      in 92% of patients with small AN in this series. Screening ABR was abnormal in
      approximately 19% of cases, one-third of which were found to have AN on magnetic
      resonance imaging testing. CONCLUSION: With strict adherence to optimal technique
      and evaluation criteria, the ABR remains a viable option for AN screening,
      especially in elderly patients or when there is a low index of suspicion.

PMID- 10890736
TI  - Gene therapy using hematopoietic stem cells: Sisyphus approaches the crest.
AB  - Gene transfer targeting cells of the blood and immune system was one of the first
      areas of investigation in the field of gene therapy. Despite the encouraging
      results achieved in early studies using murine bone marrow, the task of gene
      transfer into human hematopoietic stem cells proved to be far more difficult. As
      a result, progress has been disappointingly slow and initial clinical trials
      generally failed to achieve significant levels of gene marking. The continued
      application of new advances in vectorology and hematopoietic stem cell biology
      has now led to improvements in preclinical models that are being translated into
      clinical trials. The progress and remaining problems are discussed in this review
      article.

PMID- 10890737
TI  - Immunological gene therapy with ex vivo gene-modified tumor cells: a critique and
      a reappraisal.
AB  - Studies using animal models have demonstrated that transduction of genes encoding
      different cytokines into tumor cells results in a local recruitment of
      inflammatory cells that in turn can inhibit tumor growth. This is often
      accompanied by tumor antigen priming of the host immune system, which becomes
      resistant to subsequent challenge by the parental, untransduced tumor. Gene
      transduced tumor cells have therefore been widely used as vaccines, although in
      the therapeutic setting their antitumor efficacy was limited to a few animal
      models. On the basis of this rationale, clinical studies were initiated, results
      of which are evaluated in this review to identify the reasons for their limited
      efficacy. We point out problems generated by the use of autologous versus
      allogeneic gene-transduced vaccines, by the choice of the appropriate
      cytokine(s), and by patient selection. Results of these studies are also compared
      with those obtained by peptide-based vaccines in similar groups of patients.
      Altogether, we conclude that improvements can be made in the construction of gene
      modified vaccines by (1) using tumor cells known to express molecularly defined
      antigens, (2) introducing, in addition to genes encoding cytokines, genes
      encoding T cell costimulatory molecules, (3) increasing the amount of cytokine
      released locally by irradiated cells, and (4) coadministering adjuvant cytokines
      (IL-2 and IL-12) systemically in order to expand the T cell pool activated by
      vaccines.

PMID- 10890738
TI  - Systemic production of human granulocyte colony-stimulating factor in nonhuman
      primates by transplantation of genetically modified myoblasts.
AB  - Clinical use of human granulocyte-colony stimulating factor (hG-CSF) to treat
      various diseases involving neutropenia has been previously shown to (1)
      successfully increase circulating neutrophils, (2) reduce condition-related
      infections, and (3) cause few side effects in patients. To alleviate the symptoms
      of neutropenia, the patient must receive frequent injections of recombinant hG
      CSF. Permanent ways to deliver stable levels of the molecule to the patient are
      being investigated. Among them, the transplantation of hG-CSF-secreting cells has
      been proposed and performed successfully in rodents, using fibroblast cell lines
      and primary muscle cells. We thus investigated whether similar results could be
      obtained by intramuscular myoblast transplantation in a large animal model. When
      1-3 x 10(8) myoblasts were injected into three Macaca mulatta, hG-CSF was
      detected at high levels (300-900 pg/ml), which in turn led to a four- to fivefold
      increase in circulating neutrophils. However, both the concentrations of hG-CSF
      and neutrophil levels were found to decrease over time. Nonetheless, neutrophils
      were found at higher levels from the fourth week until the end the experiment (up
      to 29 weeks) in G-CSF monkeys compared with control animals. These results show
      that transplantation of hG-CSF-secreting myoblasts may indeed be a therapeutic
      option for the treatment of neutropenic patients.

PMID- 10890739
TI  - Immunogenicity of whole-cell tumor preparations infected with the ALVAC viral
      vector.
AB  - The immunogenicity of recombinant canarypox (ALVAC) viral vectors within murine
      whole-cell tumor vaccines was evaluated using the T cell thymic lymphoma STF10
      and the B16 melanoma. Tumor cells were modified with the recombinant ALVAC
      vectors and injected into syngeneic mice. Control mice receiving cells alone all
      developed tumors, while mice injected with tumor variants bearing parental and
      recombinant vectors either completely rejected their tumors, or exhibited a
      significant delay in tumor formation. Rechallenge of mice receiving STF10-variant
      vaccines yielded a protective effect against parental tumor cells only when a
      modified regimen incorporating two vaccinations was utilized. Notably, the
      parental ALVAC virus was equivalent to all other recombinant ALVAC viruses in
      conferring antitumor immunity when using a prime-and-boost protocol.
      Tumorigenicity experiments in nude mice revealed that the effector mechanism
      mediating rejection of tumor cells bearing ALVAC vectors is multifactorial, in
      that the immunogenicity of STF10/ALVAC vaccines is reduced, but not completely
      abolished in these mice. Finally, in vitro experiments revealed that cytotoxic T
      cells specific for parental STF10 cells could be generated as a result of in vivo
      immunization with STF10/ALVAC vaccines.

PMID- 10890740
TI  - Potential of allospecific gene-engineered T cells in transplantation gene
      therapy: specific T cell activation determines transgene expression in vitro and
      in vivo.
AB  - T lymphocytes, regardless of their specificity, are considered key targets for
      genetic modification in the treatment of inherited or acquired human diseases. In
      this study, we generated Lewis T cell lines specific for Dark Agouti rat
      alloantigens and tested the potential of allospecific T lymphocytes as carriers
      of genes encoding therapeutic proteins in transplantation gene therapy. These
      allospecific T lymphocytes were successfully, stably transduced with enhanced
      green fluorescent protein (EGFP) by an Mo-MuLV-based retrovirus vector. A novel
      gene delivery protocol was utilized, resulting in nearly 100% EGFP-expressing T
      cells. This approach enabled tracking of allospecific transduced T cells in vivo
      and illustrates their transgene production by fluorometric determination after ex
      vivo isolation. Quantitation of EGFP transgene expression was used to determine
      the influence of T cell receptor-specific activation on transgene regulation. A
      strict positive correlation between activation state and expression level was
      detected in vitro and in vivo. The activation-induced increase in transgene
      expression could be blocked by interference with T cell activation signaling
      pathways by cyclosporin A, anti-CD4 MAb, or CTLA4-Ig. These data provide strong
      evidence that direct or indirect effects caused by activation-induced
      transcription factors are crucial in transgene upregulation. Allospecific
      activation in spleens, lymph nodes, and transplanted grafts can be considered as
      antigen-specific targeting strategy. This activation might be useful in
      expressing therapeutic proteins such as TGF-beta or IL-10 specific to these
      sites. T lymphocyte priming and activation might be prevented or altered by
      modification of the local microenvironments, thereby exerting a therapeutic
      influence on acute and chronic graft rejection processes.

PMID- 10890741
TI  - Efficient adenoviral vector transduction of human hematopoietic SCID-repopulating
      and long-term culture-initiating cells.
AB  - This article presents our studies on the adenoviral transduction efficiency,
      level of transgene expression, cell cycle status, and multilineage reconstitution
      ability of human CD34+ hematopoietic cells transduced under proliferating and
      survival growth conditions. Bone marrow and umbilical cord blood CD34+ cells were
      cultured in serum-free medium under survival conditions with thrombopoietin (Tpo)
      alone, or under proliferating conditions with Tpo, c-Kit ligand (KL), and Flt3
      ligand (FL). Adenoviral vectors carrying the enhanced green fluorescent protein
      (EGFP) gene under the control of the PGK-1 promoter were used to transduce CD34+
      cells. Approximately 10% of CD34+ cells were EGFP+ under both culture conditions.
      In contrast, up to 50% of CD34+CD38- cells were EGFP+, whereas a maximum of 8% of
      CD34+CD38(high) cells were EGFP+ (p < 0.001). Both colony-forming unit cells (CFU
      C) and 5-week long-term culture-initiating cells (LTC-ICs) were efficiently
      transduced. Under survival conditions, a substantial fraction of transduced CD34+
      cells remained quiescent. The nondividing CD34+EGFP+ cells contained LTC-ICs
      capable of reconstituting longterm culture for as long as 10 weeks. CD34+EGFP+
      cells also retained the ability to engraft and multilineage-reconstitute NOD/SCID
      mice. These observations demonstrate that primitive human hematopoietic
      progenitor cells can be efficiently transduced by adenoviral vectors.

PMID- 10890742
TI  - Percutaneous gene therapy using recombinant adenoviruses encoding human herpes
      simplex virus thymidine kinase, human PAI-1, and human NOS3 in balloon-injured
      porcine coronary arteries.
AB  - Local intracoronary delivery of recombinant adenoviruses expressing anti
      migratory or anti-proliferative proteins including human constitutive endothelial
      nitric oxide synthase (NOS3), plasminogen activator inhibitor 1 (PAI-1), or
      herpesvirus thymidine kinase (TK) (combined with ganciclovir) was used to prevent
      neointimal formation in porcine coronary arteries. After balloon injury of the
      left anterior descending (LAD) coronary artery, animals received an intramural
      injection of adenovirus (1.5 X 10(9) PFU) carrying either the NOS3 cDNA
      (AdCMVNOS3, n = 12), the PAI-1 cDNA (AdCMVPAI-1, n = 12), the TK cDNA (AdMLPItk,
      n = 12), or no cDNA (AdpL+, n = 12). After 28 days, morphometric analysis was
      performed on coronary sections from all segments demonstrating injury. The
      internal elastic lamina (IEL) fracture length normalized to the IEL perimeter
      (initial injury) and the neointimal area normalized to the vessel area (response
      to injury) were used to generate linear regression lines and calculate an index
      of stenosis for the respective treatment groups. The response to injury was
      significantly smaller in AdCMVNOS3- and AdMLPItk-infected animals than in AdpL+
      infected animals (slopes = 0.86 +/- 0.05 and 0.69 +/- 0.07 versus 1.11 +/- 0.06,
      p < 0.005 and p < 0.0001, respectively) but not in AdCMVPAI-1-infected animals
      (slope = 1.26 +/- 0.04, p = 0.04). No viral shedding was observed and there was
      no acute systemic toxicity after gene transfer. An increase in neutralizing
      antibody titers against Ad vectors was observed without any detectable response
      to the transgene products (NOS3, PAI-1). Local gene transfer of NOS3 and TK may
      hold promise as a safe and effective adjunctive treatment to reduce neointimal
      formation after percutaneous coronary intervention in humans.

PMID- 10890743
TI  - Protease-deleted adenovirus vectors and complementing cell lines: potential
      applications of single-round replication mutants for vaccination and gene
      therapy.
AB  - A new kind of versatile adenoviral vector (AdV) has been constructed, one that is
      completely replication disabled in the absence of Ad-E1 proteins but is capable
      of a single round of replication when Ad-E1 is present. This was made possible by
      deletion of the Ad protease gene (PS), which is essential for many steps of the
      Ad life cycle. The PS-deleted virus can be propagated in 293-derived cell lines
      engineered to express PS. In these new complementing cells, the PS gene was
      expressed from a tetracycline-inducible promoter in a dicistronic vector
      coexpressing the green fluorescent protein (GFP). When induced, the best 293-PS
      stable clones produced the PS in amounts greater than the level reached after Ad
      infection. Biological activity was first demonstrated by the ability of 293-PS
      cells to support the replication of Ad2ts1, a mutant expressing a functionally
      defective PS. While overexpression of the Ad PS slightly affected cell growth,
      moderate expression at levels sufficient to fully complement Ad2ts1 was well
      tolerated in 293 cells. Two PS-deleted mutants, deleted or not deleted for E1/E3,
      were then generated and characterized. Despite their complete loss of infectivity
      after a single round of replication in permissive cells, the PS-deleted mutants
      produced as much viral protein as wildtype Ad. These new vectors should thus be
      both safer and more efficient for applications in which enhancement of transgene
      expression is desirable, as in the case of vaccination, in situ therapy for
      tumors, protein production, or the large-scale production of other viral vectors
      such as adeno-associated virus (AAV).

PMID- 10890744
TI  - A phase I study using direct combination DNA injections for the immunotherapy of
      metastatic melanoma. University of Colorado Cancer Center Clinical Trial.

PMID- 10890745
TI  - High-performance liquid chromatographic analysis of saponin compounds in
      Bupleurum falcatum.
AB  - A mixture of saponin compounds (saikosaponin c, a, and d) in the 70% ethanol
      extract of a powdered sample of Bupleuri radix are analyzed by an Inertsil ODS-3
      C(18) column at a flow rate of 1.0 mL/min and detection wavelength of 203 nm.
      Well resolved chromatograms of saikosaponin c, a, and d are obtained with a
      gradient elution of acetonitrile-water from 40:60 (v/v) to 50:50 (v/v). The total
      time required for a single analysis is approximately 20 min. Calibration curves
      for saikosaponin c, a, and d are linear up to 2.5 mg/mL. The coefficient of
      variability values for saikosaponins in the extract are below 4%, and the
      recoveries for saikosaponin c, a, and d are 95.2 +/- 1.1, 96.5 +/- 0.9, and 96.2
      +/- 1.0%, respectively. The changes in saikosaponin contents for a two-year
      growth of Bupleurum falcatum are measured by the established high-performance
      liquid chromatography method.

PMID- 10890747
TI  - SSTS-Ajax for analysis on-line by gas chromatography
AB  - A switching system of triplet samples (SSTS-Ajax) is introduced to the analysis
      on-line by gas chromatography. The triplet samples (i.e., a sample and its two
      duplicates) can be obtained at the same time and then analyzed in turn by using
      this system. During a reaction, if the analysis of one sample is unsuccessful or
      the result is abnormal, a duplicate can be kept for a second analysis in the
      sampling tube without the following on-line analyses interrupted. Alternatively,
      the triplet samples can be respectively analyzed under different operating
      conditions, and thus offer more information about the sample. Furthermore, the
      triplet samples from different points on-line can be obtained alternately or even
      at the same time with the aforementioned advantages maintained. In addition, six
      samples from one point on-line can also be obtained at the same time or even at
      six different times and then analyzed one by one, which is very helpful when the
      duration of an analysis is much longer than the interval of two continuous
      sampling operations. The principle and usage of SSTS-Ajax is discussed in detail.

PMID- 10890746
TI  - Rapid screening of natural products by high-resolution high-temperature gas
      chromatography.
AB  - The crude ethanol extracts from the leaves of three Croton hemiargyrus
      hemiargyreus plants are fractionated by thin-layer chromatography, yielding five
      fractions. The fractions and the crude extract are analyzed by high-temperature
      high-resolution gas chromatography coupled with mass spectrometry (HT-HRGC-MS).
      Several natural products, including thermolabile components, can be characterized
      directly in the samples, such as alkaloids, terpenes, flavonoids, acids,
      alcohols, etc. The cold on-column technique proves to be appropriate for the
      injection of these thermolabile compounds. HT-HRGC-MS is shown to be a valuable
      tool and an alternative technique to classical phytochemical procedures for the
      simple and fast routine analysis of natural products in crude extracts.

PMID- 10890748
TI  - Validation of a high-performance liquid chromatography method for the assay of
      and determination of related organic impurities in nevirapine drug substance.
AB  - Nevirapine (Viramune), a dipyridiodiazepinone, is a potent and highly specific
      nonnucleoside inhibitor of HIV-1 reverse transcriptase. This paper describes the
      validation of a specific, sensitive, and stability-indicating high-performance
      liquid chromatography method for the assay and determination of related organic
      impurities in nevirapine drug substance. This method uses a Supelcosil LC-ABZ
      column, a mobile phase of 20:80 (v/v) acetonitrile-25mM NH4H2PO4 (pH 5.0), and
      ultraviolet detection at a wavelength of 220 nm. This method was validated for
      specificity, linearity, accuracy, repeatability, detection limit, quantitation
      limit, stability of analyte solutions, robustness, and intermediate precision.
      Nevirapine is completely separated from all impurities. The method is shown to be
      linear with coefficients of determination r2 greater than 0.999. Average accuracy
      is 100.4% with a relative standard deviation of 0.7% for the assay. Accuracy
      ranges from 100.1 to 102.6% for related organic impurities. Repeatability is
      good, with relative standard deviations not more than 1.4%. The detection limit
      and the quantitation limit are determined to be 0.001 and 0.003%, respectively.
      Relative response factors of known organic impurities are determined, permitting
      the use of nevirapine at the 0.1% level as an external standard for the
      quantitation of these impurities. Analyte solutions are shown to be stable for at
      least 2 days at ambient temperature. The method is validated as robust, and
      intermediate precision is high. A system suitability test is developed and
      validated, and requirements are set.

PMID- 10890749
TI  - High-throughput method development approaches for bioanalytical mass
      spectrometry.
AB  - A rational approach to the development and optimization of solid-phase extraction
      (SPE) methods is described. The semiautomated scheme allows for the simultaneous
      testing of multiple chemistries using a custom multiple-sorbent 96-well method
      development plate. Optimized extraction conditions for up to five analytes are
      determined in a single 2.5-h experiment. The experiment can be tailored to
      determine SPE conditions (including wash protocols) for related analytes. Data
      obtained by liquid chromatography-atmospheric pressure ionization-mass
      spectrometry allows the quantitation of absolute recovery and selection of the
      best extraction conditions for approximately 100 analytes of diverse structure.
      Optimized extraction protocols yielding at least 80% recovery are determined for
      81% of the analytes. For 96% of the analytes screened, extraction conditions
      resulting in recoveries of > or = 60% are determined. The most generic set of SPE
      conditions consist of either C8 or C18 sorbent with an eluent composition of
      acetonitrile with 5mM nitric acid added.

PMID- 10890751
TI  - Gas chromatography problem solving and troubleshooting

PMID- 10890750
TI  - A simple high-performance liquid chromatography method for the analysis of
      glucose, glycerol, and methanol in a bioprocess.
AB  - A reliable high-performance liquid chromatography-refractive index detection
      method for the simultaneous analysis of glucose, methanol, and glycerol in a
      bioprocess fermentation media using direct injection is presented. The validation
      studies show a satisfactory selectivity, linearity, accuracy, and recovery of the
      method. The lowest concentration detectable for glucose and methanol is 3.5 and
      6.7 mg/100 mL, respectively. This method could be an attractive choice for the
      analysis of these compounds not only in fermentation media but also in biomedical
      and environmental samples.

PMID- 10890752
TI  - Liquid chromatography problem solving and troubleshooting

PMID- 10890753
TI  - Genotypic and environmental effects on lupin seed composition.
AB  - Currently, white lupin (Lupinus albus L.) is gaining importance due to its high
      nitrogen fixation capability and potential in sustainable crop production
      systems. Even though research conducted in Australia, Chile, Germany, New
      Zealand, and Portugal has indicated lupin's positive potential as human and
      animal food, such information from Virginia and adjoining areas of the United
      States is not available. In addition, effects of growing environment and
      genotypes on lupin seed composition need to be characterized to evaluate lupin's
      potential as a food and feed crop. Towards this end, seed of 12 lupin genotypes
      produced in Maine (USA) and Virginia (USA) were compared to determine genotypic
      and environmental effects on contents of protein, sugar, oil, various fatty
      acids, amino acids, and minerals. The protein content of dry seed was not
      affected by growing environment. However, growing environment had significant
      effects on contents of total sugar, amino acids, oil, fatty acids, and minerals.
      Significant variation existed among 12 lupin genotypes for various traits when
      composition of seed produced in Virginia was evaluated. The results indicated
      that site-specific evaluation of adapted lupin genotypes for chemical composition
      should be included in efforts to evaluate lupin's overall potential as a food or
      feed crop.

PMID- 10890754
TI  - Guar gum effects on food intake, blood serum lipids and glucose levels of Wistar
      rats.
AB  - The effects of guar gum derived from the endosperm of Cyamopsis tetragonoloba
      (75% soluble fiber, 7.6% insoluble fiber, 2.16% crude protein, 0.78% total
      lipids, 0.54% ash and 9.55% moisture) on food intake, levels of blood serum
      cholesterol, triacylglycerols, glucose and LDL and HDL-cholesterol were studied.
      The effects of guar gum on indices of protein absorption and utilization were
      also investigated. Diets containing 0%, 10% and 20% (w/w) guar gum or 10% and 20%
      cellulose powder (reference) were fed to normal rats for 60 days. The rats fed
      the guar gum diets showed significantly (p < or = 0.05) lower levels of blood
      serum cholesterol, triacylglycerols, reduced food intake and body weight gain.
      Furthermore, a concomitant increase in HDL-cholesterol with a substantial
      elevation of the HDL/LDL cholesterol ratio were noted. Guar gum decreased blood
      serum glucose only during the first month of the experiment, and no changes in
      the indices of protein absorption and utilization were found. The guar gum caused
      a 10% increase in the small intestine length and a 25% retardation in the
      intestinal transit. The results of this research suggested that guar gum could
      potentially be effective in the treatment of hypercholesterolemia and obesity in
      humans.

PMID- 10890755
TI  - Mineral composition of non-conventional leafy vegetables.
AB  - Six non-conventional leafy vegetables consumed largely by the rural populace of
      Nigeria were analyzed for mineral composition. Mineral contents appeared to be
      dependent on the type of vegetables. Amaranthus spinosus and Adansonia digitata
      leaves contained the highest level of iron (38.4 mg/100 g and 30.6 mg/100 g dw,
      respectively). These values are low compared to those for common Nigerian
      vegetables but higher than those for other food sources. All the vegetables
      contained high levels of calcium compared to common vegetables, thus they could
      be a rich source of this mineral. Microelement content of the leaves varied
      appreciably. Zinc content was highest in Moringa oleifera, Adansonia digitata and
      Cassia tora leaves (25.5 mg/100 g, 22.4 mg/100 g and 20.9 mg/100 g dw,
      respectively) while the manganese content was comparatively higher in Colocasia
      esculenta. The concentrations of the mineral elements in the vegetables per
      serving portion are presented and these values indicate that the local vegetables
      could be valuable and important contributors in the diets of the rural and urban
      people of Nigeria. The mean daily intake of P, Mg, Ca, Fe, Cu and Zn were lower
      than their recommended dietary allowances (RDAs). However, the manganese daily
      intake was found not to differ significantly (p = 0.05) from the RDA value.

PMID- 10890756
TI  - Effects of extrusion cooking on functional properties of mixtures of full-fat soy
      and sweet potato.
AB  - Full-fat soy and sweet potato were extruded at 0:100, 25:75, 50:50, 75:25 and
      100:0 ratios in an Insta-Pro 600 single screw extruder operated at 180, 200, 220
      rpm respectively. Functional properties: bulk density, expansion ratio, water
      absorption and solubility indices and trypsin inhibitor were assayed. Results
      showed that addition of soybeans to sweet potatoes considerably increased the
      protein, fat, ash and trypsin inhibitor levels of the raw material mixtures. It
      also led to decreases in viscosities of raw mixtures, with corresponding
      increases in pasting temperatures. Addition of soybean significantly (p <0.05)
      affected expansion ratio, water absorption and solubility indices and trypsin
      inhibitor but not bulk density. Variation in screw rotation speed (rpm)
      significantly (p <0.05) affected only water solubility index at increasing speed.
      Extrudates generally received severe heat treatment, rendering them applicable
      only in soup bases, flour mixes and breakfast foods.

PMID- 10890757
TI  - Characterization of starches of proso, foxtail, barnyard, kodo, and little
      millets.
AB  - Scanning electron microscope (SEM) pictures of small millet starch granules
      showed more large polygonal and few small spherical or polygonal granules. The
      granules of small millets resembled those of rice starch granules. The size of
      the starch granules ranged from 0.8-10 microm. The size of the granules was
      larger in barnyard millet and smaller in proso millet. Several granules showed
      deep indentation caused by protein bodies. SEM of starch isolated from 24 hour
      germinated kodo millet showed pitting or pinholes at some points due to the
      attack of amylases (preferentially on bigger granules). Brabender viscoamylograph
      studies on small millet starches revealed that the gelatinization temperatures
      ranged from 75.8 to 84.9 degrees C. Barnyard millet possessed lower amylograph
      viscosity, minimum breakdown, and relative breakdown values when compared to the
      other small millets.

PMID- 10890758
TI  - Nutrient content of the edible leaves of seven wild plants from Niger.
AB  - Wild plants play an important role in the diet of the inhabitants of Niger. These
      plants tend to be drought-resistant and are gathered both in times of plenty as
      well as times of need. Used in everyday cooking, famine foods may be an important
      source of nutrients. The goal of this study was to investigate the nutritional
      role of wild plants in the nigerien diet. To this end, leaves of seven plants
      species were analyzed for their mineral, amino acid and fatty acid contents:
      Ximenia americana, Amaranthus viridus, Corchorus tridens, Hibiscus sabdarifa,
      Maerua crassifolia, Moringa oleifera, and Leptadenia hastata. Ximenia americana
      contained large amounts of calcium. Large quantities of iron were present in
      Amaranthus viridus. All seven plants contained significant amounts of selenium
      and phosphorus. Corchorus tridens contained the most protein (19-25% dry weight),
      and its composition compared favorably to the World Health Organization's
      standard for essential amino acids. Moringa oleifera contained 17% protein and
      compared favorably with the WHO standard. Corchorus tridens contained the largest
      amounts of the two essential fatty acids linoleic and alpha-linolenic acids.
      These results reinforce the growing awareness that wild edible plants of the
      Western Sahel can contribute useful amounts of essential nutrients, including
      amino acids, fatty acids and trace minerals, to human diets.

PMID- 10890759
TI  - Selected mineral content of common leafy vegetables consumed in India at
      different stages of maturity.
AB  - Micromineral contents were estimated in commonly consumed green leafy vegetables:
      Koyyathotakura and Peddathotakura (varieties of Amaranthus species); Erragogu and
      Tellagogu (variety of Hibiscus species) Gangabayalakura and palak at three
      different stages of maturity. Varietal differences were also observed. The
      results of the study showed that as the plant matured from stage 1 (15 days) to
      stage II (30 days), iron and manganese contents increased whereas zinc and copper
      contents decreased as the plant matured. Varietal differences were also observed
      at different stages of maturity. The results also indicated that the consumption
      of green leafy vegetables at stage I and stage II potentially provides the
      greatest amount of a mineral.

PMID- 10890760
TI  - Effect of inclusion of cashew globulin (Anacardium occidentale) to a casein diet
      on lipid parameters in rats.
AB  - The effect of inclusion of cashew globulin to a casein diet on lipid metabolism
      was studied in rats fed diets with two levels of cashew globulin meal. Inclusion
      of cashew globulin to a casein diet produced lower levels of total cholesterol,
      triacylglycerol and phospholipids in the serum and tissues and lower levels of
      serum lipoprotein cholesterol. There was decreased cholesterogenesis in the liver
      as evidenced by decreased activity of HMG CoA reductase and decreased release of
      lipoproteins into circulation. Rats fed cashew globulin along with casein also
      showed higher activity of LPL in the heart and adipose tissue and higher activity
      of LCAT. Increased hepatic diversion of cholesterol to bile acid synthesis and
      increased excretion of bile acids and sterols were also observed in these groups.
      Activity of glucose-6-phosphate dehydrogenase and malic enzyme was decreased in
      rats fed cashew globulin along with casein. This study demonstrates that cashew
      globulins included in the diet of rats are able to alter lipid metabolism which
      results in lower levels of lipid parameters in the serum and tissues.

PMID- 10890761
TI  - Evaluation of surgical approaches to endoscopic auditory brainstem implantation.
AB  - OBJECTIVES: This study investigates the use of endoscopy for the placement of an
      auditory brainstem implant by translabyrinthine, retrosigmoid (suboccipital), and
      middle cranial fossa approaches. STUDY DESIGN: Cadaver dissection and endoscope
      assisted placement of the auditory brainstem implant. METHODS: Translabyrinthine,
      retrosigmoid, and middle cranial fossa dissections were performed bilaterally in
      five cadaveric heads. An auditory brainstem implant was placed within the lateral
      recess of the fourth ventricle under endoscopic visualization. The implantation
      was performed with all approaches and documented by digital image capture
      followed by production of dye-sublimation photographic prints. RESULTS: The
      lateral recess was visualized with the endoscope in all three approaches to the
      brainstem. The 30 degrees endoscope provided the best visualization by
      translabyrinthine and retrosigmoid dissection and was essential for the middle
      cranial fossa approach. Refinement of implant position was readily achieved, as
      even the deepest portion of the recess could be seen with all three approaches.
      CONCLUSIONS: This study finds that endoscopy provides superior visualization of
      the lateral recess of the fourth ventricle than the operating microscope with all
      approaches. The retrosigmoid approach is recommended, as it provides the best
      view of the implantation site and the easiest angle for placement of the
      prosthesis. The use of the endoscope may allow for a smaller craniotomy than with
      conventional microscopic techniques, depending on tumor size. The
      translabyrinthine approach provides a good view of the lateral recess but had no
      advantage over other approaches. The middle cranial fossa approach is only
      possible with angled endoscopes; however, it is technically the most difficult
      and places the facial nerve at greatest risk.

PMID- 10890762
TI  - Cochlear implantation in auditory neuropathy.
AB  - OBJECTIVE: Auditory neuropathy is a recently described clinical entity
      characterized by sensorineural hearing loss in which the auditory evoked
      potential (ABR) is absent but otoacoustic emissions are present. This suggests a
      central locus for the associated hearing loss. In this study the results observed
      in a child with auditory neuropathy who received a cochlear implant are presented
      and compared with those of a matched group of children who were recipients of
      implants. METHODS: A single-subject, repeated-measures design, evaluating closed
      set and open-set word recognition abilities was used to assess the subject and a
      control group of matched children with implants who had also experienced a
      progressive sensorineural hearing loss. RESULTS: The subject demonstrated
      improvements in vowel recognition (82% correct) by 1 year after implantation,
      which were only slightly lower than the control group. Consonant recognition and
      open-set word recognition scores were significantly lower. CONCLUSION: Caution
      should be exercised when considering cochlear implantation in children with
      auditory neuropathy. As with conventional hearing aids, less than optimal results
      may be seen.

PMID- 10890763
TI  - Comparison of the auditory-evoked brainstem response wave I to distortion-product
      otoacoustic emissions resulting from changes to inner ear blood flow.
AB  - OBJECTIVE/HYPOTHESIS: Examine and compare in detail the time courses of the
      auditory brainstem response (ABR) wave I amplitude and latency to the distortion
      product otoacoustic emission (DPOAE) amplitude and phase measured in the rabbit
      model following deliberate obstruction of cochlear blood flow (CBF). METHODS:
      Using a posterior fossa craniotomy in five rabbits, the internal auditory artery
      (IAA) was compressed with a probe. ABR and otoacoustic emission were continuously
      monitored before, during, and after the compressions. RESULTS: ABR wave I
      amplitudes demonstrated measurable decreases at a mean of 28.3 s after IAA
      compression, whereas DPOAE amplitudes decreased after a mean of 14.8 s. Wave I
      latencies began to increase at a mean of 18.3 s after occlusion, while DPOAE
      phase measures changed after a mean of only 4.8 s following IAA compression. The
      time-course patterns were similar for the amplitudes of both ABR wave I and
      DPOAE. CONCLUSIONS: ABR wave I amplitude follows a similar, though delayed (by
      approximately 10 s) time-course pattern to that of the DPOAE following IAA
      compression. The implication of these findings for intraoperative auditory
      monitoring is that changes in many currently employed measures will lag actual
      surgically induced alterations in CBF by at least 20 to 30 s.

PMID- 10890765
TI  - Complications of rhytidectomy in an otolaryngology training program.
AB  - OBJECTIVES/HYPOTHESIS: Complications of rhytidectomy have been widely reported in
      the literature. This study examines the incidence of complications after
      rhytidectomy in the hands of chief residents under appropriate attending
      supervision in an otolaryngology-head and neck surgery training program.
      MATERIALS AND METHODS: The charts of 96 consecutive SMAS rhytidectomy patients
      were retrospectively reviewed. Patients were selected for surgery from a clinic
      designed exclusively for cosmetic facial surgery patients. This clinic was run by
      the otolaryngology chief resident and was supervised by an attending staff
      surgeon. Most patients elected local anesthesia and sedation administered by the
      surgical team. Submental liposuction was performed followed by SMAS plication
      rhytidectomy. RESULTS: Follow-up ranged from 1 to 60 months. Complications
      included expanding hematoma (1%), temporary facial nerve weakness (3%),
      pretragal/mastoid skin slough (4.2%), permanent ear numbness (1%), hypertrophic
      scar (3.1%), wound infection (1%), and dissatisfaction with result (4%). There
      were no cases of permanent facial nerve injury. CONCLUSION: These complication
      rates compare favorably with reported rates of larger studies over the past 30
      years. These data support the conclusion that rhytidectomy can be performed
      safely by otolaryngology residents with little morbidity and good patient
      satisfaction.

PMID- 10890764
TI  - Congenital absence of the long process of the incus.
AB  - OBJECTIVE/HYPOTHESIS: To review the case reports of three generations of one
      family, suffering from bilateral conductive hearing loss due to congenital
      absence of the long process of the incus. STUDY DESIGN: Review of the literature
      regarding hereditary congenital absence of the long process of the incus to
      determine its mode of inheritance such as autosomal dominant or X-linked. Also
      document the types and results of surgical repairs performed by previous
      investigators of this defect and compare them with the present study. METHODS:
      Three female patients of direct lineage. Mother, daughter, and granddaughter, who
      were personally seen, operated on, and followed up over a period of 26 years.
      RESULTS: All three female patients presented with similar symptoms and findings
      of hearing impairment since birth, with no history of ear infections, and with
      normal appearing tympanic membranes. However, they had severe conductive hearing
      loss with normal bone conduction and discrimination. Operative findings were
      identical in all three patients, with the incus ending in a blind stub, and with
      absence of the capitulum of the stapes. The type of ossicular reconstruction
      varied with the changing of times and advances in otologic surgery, as well as
      the prosthetic materials used. All three patients received improvement in their
      hearing, and this improvement has been maintained over the 26-year span of the
      study. CONCLUSIONS: Hearing loss due to congenital absence of the incus is
      uncommon but not rare. Interestingly, no other instance of inherited cases were
      reported in the literature. In this family the defect appears to be an inherited
      trait either due to an autosomal dominant mutation or an X-linked dominant
      inheritance. This abnormality is amendable to surgery, and any well-executed
      technique usually gives good hearing results.

PMID- 10890766
TI  - Plasma adrenaline concentrations during functional endoscopic sinus surgery.
AB  - OBJECTIVES/HYPOTHESIS: Vasoconstrictors (i.e., epinephrine) are routinely applied
      before functional endoscopic sinus surgery (FESS) but may have significant
      cardiac side effects. The controversy concerning clinical application of
      adrenaline is discussed. STUDY DESIGN: In a prospectively controlled study of 51
      patients undergoing FESS we evaluated the absorption of adrenaline from standard
      cotton pledgets and submucous infiltration and the incidence of related side
      effects during surgery. Additionally, a control group of 12 patients undergoing
      tonsillectomy was investigated. METHODS: Plasma adrenaline concentrations were
      measured 1) before anesthesia, 2) after intubation, 3) after nasal packing with
      adrenaline soaked pledgets (adrenaline 1:1000) and submucous infiltration with 2
      mL lidocaine with adrenaline 1:100,000 in each side, and 4) at end of surgery.
      The catecholamines were determined with a Merck-Hitachi Catecholamine Analyzer,
      model II (Merck, Darmstadt, Germany). Pulse, electrocardiogram (ECG), and blood
      pressure were monitored. RESULTS: In the FESS group, we found a remarkable
      decrease in systolic (S) as well as diastolic blood pressure (D) (P < .001),
      whereas the heart frequency was unaffected during surgery. All patients in the
      adrenaline group showed significant increase in plasma adrenaline (AD)
      concentrations in the third and fourth sample (P < .001). The control group,
      however, showed a significant rise in blood pressure only at beginning of surgery
      (P < .001) with cardiac pulse and plasma adrenaline concentrations unaffected by
      surgery or anesthesia. The often described severe side effects of adrenaline in
      combination with general anesthesia were not seen in any of our patients.
      CONCLUSIONS: Although systemic absorption of locally injected vasoconstrictors
      occurs, adrenaline-related side effects during FESS are extremely rare when the
      patient is monitored exactly.

PMID- 10890767
TI  - Management options and survival in malignant melanoma of the sinonasal mucosa.
AB  - OBJECTIVES/METHODS: To determine whether surgery combined with radiotherapy
      confers any survival benefit on radical local excision alone in the management of
      mucosal malignant melanoma of the nose and sinuses. STUDY DESIGN: Retrospective
      review. METHODS: From a cohort of 72 patients treated between 1963 and 1996
      within a single unit, complete data were available for 58 individuals who were
      examined to determine whether there was any significant statistical difference in
      local control and/or survival between those receiving surgery and those receiving
      combined surgery and radiotherapy. RESULTS: There were 30 men and 28 women. Their
      ages ranged from 39 to 90 years (mean, 64 y). Twenty-nine patients underwent
      surgery alone; 23 patients underwent surgery and radiotherapy; 6 patients
      received surgery and chemotherapy; and 3 patients received surgery, chemotherapy,
      and radiotherapy. Primary surgery included lateral rhinotomy (42 cases),
      maxillectomy (8 cases [orbital clearance in 3 cases]), craniofacial resection (3
      cases), total rhinectomy (3 cases), and endoscopic clearance (2 cases). Survival
      ranged from 1 to 228 months with rapid patient loss due to local (and/or
      systemic) disease during the first 36 months, irrespective of the treatment
      modality. Overall 5-year actuarial survival was 28%, and overall 10-year
      actuarial survival 20%, with a median survival of 21 months. There was no
      statistical difference in local control or survival between patients receiving
      surgery alone and those receiving surgery and radiotherapy, irrespective of
      whether this treatment was given in the early part of the series (i.e., before
      1983) or thereafter. The addition of chemotherapy had no impact on survival, nor
      did the site of the tumor, the surgical procedure, the presence of lymph node
      metastases or the age of the patient. CONCLUSION: In this large cohort of
      sinonasal melanoma, overall survival was poor and did not appear to be improved
      by the addition of radiotherapy.

PMID- 10890768
TI  - Extent of lymphadenectomy achieved by various modifications of neck dissection: a
      pathologic analysis.
AB  - OBJECTIVES: Quantify the extent of lymphadenectomy achieved by the various
      modifications of neck dissection based on microscopic pathologic analysis. STUDY
      DESIGN: Retrospective review of neck specimens of patients who underwent neck
      dissection for head and neck malignancies at our institution over a 5-year
      period. METHODS: Charts and pathology report findings on patients who underwent
      neck dissection were reviewed. Patients who received preoperative chemotherapy or
      radiation therapy to the neck were excluded. The number of lymph nodes documented
      by pathologic microscopic examination for each specimen was recorded. RESULTS:
      There were 164 neck specimens on 135 patients (29 patient had simultaneous
      bilateral neck dissection). Those were divided into four groups based on the
      nonlymphatic structures preserved. There were 58 radical neck dissections
      (radical neck dissections) (group 1), 50 modified radical neck dissections
      sparing the eleventh cranial nerve (group 2), 15 modified radical neck
      dissections sparing the eleventh cranial nerve and internal jugular vein (group
      3), and 33 modified radical neck dissections sparing the eleventh cranial nerve,
      internal jugular vein, and sternocleidomastoid muscle (group 4). The remaining 8
      had other modifications of radical neck dissection. The mean number of lymph
      nodes found per specimen was 34 in group 1, 27 in group 2, 31 in group 3, and 22
      in group 4. We performed one-way between-group analysis of variance (ANOVA). Pair
      wise comparisons of means were carried out subsequent to ANOVA utilizing the
      Fisher Exact Test. Group 4 was significantly different from all other groups.
      Additionally, group 2 significantly differed from group 1. CONCLUSIONS: The
      extent of lymphadenectomy achieved by neck dissection decreases as the number of
      nonlymphatic structures preserved in the neck increases. The impact of this
      finding on the pathologic staging or prognosis needs further analysis.

PMID- 10890769
TI  - In situ identification of normal visceral tissues using contact telescopic
      microscopy.
AB  - OBJECTIVES: To improve the intraoperative anatomic identification of normal
      tissues during surgery using histologic-like criteria STUDY DESIGN: A contact
      telescope was used to identify normal visceral tissues in an animal model using
      pigs and dogs during routine human surgical procedures. METHODS: Tissues that
      could be identified grossly were stained topically with methylene blue and then
      examined with the contact telescope. The histologic appearance of these tissues
      with the contact telescope was correlated with routine histologic hematoxylin and
      eosin stains obtained after such tissues were excised. RESULTS: Normal tissues,
      such as fat, blood vessels, muscle, and parathyroid tissue, can be identified
      reliably in animals and humans. The contact telescope appears to be able to
      differentiate between a variety of visceral tissues in the neck and may become
      useful for practical differentiation between tissues during surgery.

PMID- 10890770
TI  - Contralateral hemilaryngotracheal flap reconstruction of the hypopharynx in
      pyriform carcinoma resection.
AB  - OBJECTIVES: To simplify the approach and reconstruction for advanced
      hypopharyngeal cancer, a modified technique-laryngotracheal fissure approach and
      laryngotracheal flap reconstruction--is presented. STUDY DESIGN: Prospective.
      METHODS: From August 1991 to December 1995, 44 consecutive patients with advanced
      hypopharyngeal cancer, mostly involving pyriform sinus, were operated on with
      this technique. The functional and oncologic results and complications were
      evaluated. RESULTS: Reconstruction was completed by using the laryngotracheal
      flap in 75% of patients, while the other 25% required additional patch-on
      pectoralis major myocutaneous flaps. Pharyngoesophageal stenosis occurred in one
      patient after radiotherapy and pharyngocutaneous fistula was noted in two. No
      local recurrence was noted. Seven cervical metastases developed in the follow-up
      period and six over the contralateral neck not treated surgically. The 5-year
      Kaplan-Meier disease-free survival was 46.8%. CONCLUSIONS: The authors'
      experience indicates that this is a simplified, radical treatment for most
      advanced hypopharyngeal cancer, with high applicability, good oncologic results,
      and low complication.

PMID- 10890771
TI  - Three-dimensional imaging of the speaking shunt in patients with near-total
      laryngectomy.
AB  - OBJECTIVES: Near-total laryngectomy with creation of a speaking shunt is
      generally considered suitable treatment for most T3 and some T4 laryngopharyngeal
      cancers. In some patients, poor speech production by the shunt can be problematic
      and usually means that a shunt lumen is stenotic or too small. Conventional axial
      computed tomography (CT) of the neck is of little value in predicting the shunt
      function and the patency of the shunt lumen. Such defect, however, can be better
      overcome if the spiral CT is used. STUDY DESIGN: This study was designed to
      evaluate the dynamic speaking shunt by spiral CT and a three-dimensional (3-D)
      imaging model of the upper airway in 59 near-total laryngectomies. METHODS:
      During scanning, the patients were asked to make a single, 20-second phonation. A
      high-quality 3-D surface model was then rendered at an independent workstation.
      The 3-D model took on the appearance of the speaking shunt which could serve as a
      tracheopharyngeal fistulography. RESULTS: 3-D reconstruction of the images could
      clearly demonstrate the dynamic anatomy and patency of the speaking shunt. We
      found the 3-D model to be of diagnostic value, particularly in the near-total
      laryngectomy patients with stenotic shunts. The most common site of stenosis was
      at the top portion of the shunt. CONCLUSION: The 3-D image findings of the shunts
      significantly improved the assessment and therapies of the patients undergoing
      revision surgeries of the shunt stenoses.

PMID- 10890772
TI  - Squamous cell carcinoma of the sinonasal tract invading the orbit.
AB  - OBJECTIVE/HYPOTHESIS: The treatment of squamous cell carcinoma (SCC) of the
      sinonasal tract has evolved from routine exenteration of the orbital contents to
      sparing of the orbit when the SCC does not transgress the periorbita.
      Nonetheless, the influence of this change in treatment over the rate of local
      recurrence or survival has not been clearly elucidated. The objective was to
      ascertain whether orbital sparing surgery for the treatment of SCC of the
      paranasal sinuses influences the rate of local recurrence or survival. STUDY
      DESIGN: This is a retrospective study of patients presenting with SCC arising in
      the sinonasal tract, treated primarily at the University of Pittsburgh Medical
      Center from 1977 to 1990, including meta-analysis of the English literature
      regarding SCC of the sinonasal tract. METHODS: Review of medical records
      regarding demographics, histology, extension of tumor, pathologic results, type
      of surgery, adjunctive therapy, and outcome. Articles for meta-analysis were
      identified by Medline search and cross-referencing. RESULTS: Fifty-eight patients
      with orbital invasion, including bone and/or soft tissue invasion, were included
      in the study. Patients presenting with invasion of the bony orbit without soft
      tissue invasion were treated with maxillectomy and/or ethmoidectomy, sparing the
      orbital contents. Patients presenting with invasion of the orbital bones and soft
      tissues were treated with ethmoidectomy or maxillectomy, including orbital
      exenteration. At 3 years' follow-up, 52% of the patients whose orbit was
      exenterated were alive and without evidence of disease, compared with 59% of the
      patients whose orbit was spared. This difference was not statistically
      significant. Similarly, the rate of local recurrence was not statistically
      significant (P > .05). A meta-analysis of the literature revealed similar
      results. CONCLUSIONS: Our data suggest that sparing of the soft tissues of the
      orbit when the periorbita has not been transgressed by SCC does not downgrade the
      rate of cure or local control.

PMID- 10890773
TI  - Exploring endoscopic neck surgery in a porcine model.
AB  - OBJECTIVES: This study uses a porcine model to establish the feasibility of
      performing endoscopic procedures in the neck using standard techniques currently
      being employed in preperitoneal endoscopy in the abdomen. STUDY DESIGN: It is a
      pilot study presented as a case series. METHODS: Ten animals were subjected to
      anterior deep cervical fascia dissection using standard endoscopic
      instrumentation. RESULTS: Balloon dissection and CO2 insufflation poses a number
      of problems: CO2 gas dissection into the chest, CO2 gas embolism into the venous
      circulation, carotid artery occlusion, and limited visualization causing
      increased risk of injury to adjacent structures. CONCLUSION: These issues need to
      be dealt with before such a method could be employed safely in humans. However,
      with further research and development, endoscopic neck surgery may someday become
      a reality.

PMID- 10890774
TI  - Multidimensional assessment of voice characteristics after radiotherapy for early
      glottic cancer.
AB  - OBJECTIVES/HYPOTHESIS: To assess voice characteristics of patients following
      radiotherapy for early glottic cancer through a multidimensional analysis
      protocol including vocal function and voice quality measures. METHODS: Voice
      analyses were performed for 60 patients treated with radiotherapy (66 Gy/33
      fractions, 60 Gy/30 fractions, or 60 Gy/25 fractions) for early T1 glottic cancer
      and 20 matched control speakers. There was a longitudinal group of 10 patients
      for whom data were collected before as well as 6 months and 2 years after
      radiation. Furthermore, data were collected for five separate groups of 10
      patients each, before, 6 months after, 2 years after, 3 to 7 years after, and 7
      to 10 years after radiation. Vocal function was investigated by means of
      videolaryngostroboscopy, phonetography, maximum phonation time, and phonation
      quotient measures. Voice quality was assessed by means of objective acoustical
      analysis and subjective perceptual ratings by trained raters. RESULTS: Voice
      characteristics of patients were decreased before radiotherapy, improved after
      treatment, and became comparable to the voice characteristics of control speakers
      in at least 55% of the patients. Following radiotherapy, deviant voice quality
      was mainly negatively affected by increased age and stripping the vocal cord for
      initial diagnosis. Stroboscopy revealed that next to increasing age and stripping
      the vocal cord, continued smoking after treatment decreased vocal function
      following radiotherapy. CONCLUSION: Voices of patients diagnosed with early
      glottic cancer improved but did not normalize fully after radiotherapy. Stripping
      the vocal cord for initial diagnosis and continued smoking after treatment
      decreased voice characteristics. A multidimensional analysis protocol including
      perceptual and acoustical analysis of voice quality and stroboscopic analysis of
      vocal function is recommended to investigate voice characteristics following
      treatment for early glottic cancer.

PMID- 10890775
TI  - A matched control study of treatment outcome in young patients with squamous cell
      carcinoma of the head and neck.
AB  - OBJECTIVES/HYPOTHESIS: To determine if there is a difference in overall survival,
      cause-specific survival, and relapse-free rate between young patients (<40 years
      of age) with head and neck squamous cell carcinoma (HNSCC) and older patients
      (>40 years of age). STUDY DESIGN: A matched control study describing the outcome
      of 185 previously untreated HNSCC patients less than 40 years of age treated at
      the Princess Margaret Hospital, Toronto, Ontario, Canada, between 1958 and 1992.
      The young patient group was compared with a control group of older patients (> 40
      years of age) which was selected randomly from an entire cohort of patients (n =
      10,072) and matched for site, sex, and date of presentation. METHODS: The medical
      records were reviewed and data abstracted for demographic information, tobacco
      and alcohol use, family history, primary site, clinical stage, primary treatment,
      histology, the occurrence of residual or recurrent disease, salvage treatment,
      development of subsequent primaries, survival, and the eventual cause of death.
      The patient's TNM stage was reclassified according to American Joint Cancer
      Committee/Union Internationale Contre le Cancer (AJCC/UICC) 1992 criteria on the
      basis of the initial clinical description and staging investigations. A
      multivariate regression analysis was performed. To assess the importance of age
      as a prognostic factor for survival, the Cox proportion hazard model was used.
      Smoking status was also tested in the stratified Cox proportional hazard model.
      RESULTS: Tumor stage and treatment modalities were comparable in both groups. The
      5-year, cause-specific survival in both groups was not statistically different
      (72% vs. 68%, P = .91). The young patient group had a significantly better 5-year
      overall survival compared with the older patient group (68% vs. 49%, P = .0011).
      Older patients developed more subsequent primary neoplasms than the younger
      patient population (18% vs. 8%, P = .005). There were significantly more females,
      an increased incidence of oral or oropharyngeal cancer, and fewer smokers in the
      young patient group. Smoking, however, had an important impact on outcome with
      all but one patient who developed a second primary in the upper aerodigestive
      tract having smoked. Multivariate analysis showed that only disease stage and
      cancer site were significant prognostic factors for survival. CONCLUSIONS: Young
      patients with HNSCC do not have a worse prognosis than a matched older patient
      group in this case-controlled study (power > 0.75 for a minimal detectable
      difference of 10% disease-free survival between the two groups).

PMID- 10890776
TI  - Protein C deficiency in microvascular head and neck reconstruction.
AB  - OBJECTIVE: To determine the incidence of perioperative protein C deficiency in
      patients undergoing free flap reconstruction of cancer-related defects in the
      head and neck. STUDY DESIGN: Prospective case series. INTERVENTION: Ten patients
      underwent microvascular reconstruction after surgical therapy of carcinomas of
      the oral cavity or oropharynx. Coagulation studies were determined in all
      patients 72 hours after surgery. SETTING: Academic tertiary care medical center
      RESULTS: Protein C deficiency was detected in 70% of patients. One free flap
      failure was attributed to protein C deficiency. CONCLUSIONS: Vitamin K-dependent
      clotting factors are frequently deficient during the postoperative period after
      major head and neck surgery, which may result in a state of hypercoagulability.
      Protein C deficiency should be considered as a possible cause of free flap
      thrombosis in patients who undergo microvascular head and neck reconstruction.

PMID- 10890777
TI  - Safety and biological efficacy of an adeno-associated virus vector-cystic
      fibrosis transmembrane regulator (AAV-CFTR) in the cystic fibrosis maxillary
      sinus.
AB  - OBJECTIVE: The host immune response and low vector efficiency have been key
      impediments to effective cystic fibrosis transmembrane regulator (CFTR) gene
      transfer for cystic fibrosis (CF). An adeno-associated virus vector (AAV-CFTR)
      was used in a phase I dose-escalation study to transfer CFTR cDNA into
      respiratory epithelial cells of the maxillary sinus of 10 CF patients. STUDY
      DESIGN: A prospective, randomized, unblinded, dose-escalation, within-subjects,
      phase I clinical trial of AAV-CFTR was conducted. PATIENTS: Ten patients with
      previous bilateral maxillary antrostomies were treated. MAIN OUTCOME MEASURES:
      Safety, gene transfer as measured by semiquantitative polymerase chain reaction
      (PCR), and sinus transepithelial potential difference (TEPD) were measured.
      RESULTS: The highest level of gene transfer was observed in the range of 0.1-1
      AAV-CFTR vector copy per cell in biopsy specimens obtained 2 weeks after
      treatment. When tested, persistence was observed in one patient for 41 days and
      in another for 10 weeks. Dose-dependent changes in TEPD responses to
      pharmacologic intervention were observed following treatments. Little or no
      inflammatory or immune responses were observed. CONCLUSION: AAV-CFTR
      administration to the maxillary sinus results in successful, dose-dependent gene
      transfer to the maxillary sinus and alterations in sinus TEPD suggestive of a
      functional effect, with little or no cytopathic or host immune response. Further
      study is warranted for AAV vectors as they may prove useful for CFTR gene
      transfer and other in vivo gene transfer therapies. A prospective, randomized,
      double-blind, placebo-controlled, within-subjects, phase II clinical trial of the
      effect AAV-CFTR on clinical recurrence of sinusitis will determine the clinical
      efficacy of AAV gene therapy for CF.

PMID- 10890778
TI  - Analysis of HLA antigens in Japanese patients with chronic sinusitis.
AB  - OBJECTIVES: Genetic factors likely play a role in the etiology of chronic
      sinusitis and this disease is often associated with diffuse panbronchiolitis,
      which is strongly associated with HLA B54 antigen. The purpose of this study is
      to examine whether genetic factors are involved in the pathogenesis of chronic
      sinusitis. STUDY DESIGN: Eighty-two Japanese patients with intractable chronic
      sinusitis were selected on the basis of the following criteria: 1) persistent
      mucous or mucopurulent nasal discharge and/or postnasal dripping for longer than
      3 years and 2) opacification in bilateral maxillary sinuses and ethmoid cells in
      plain X-ray films. METHODS: Both class I and class II HLA antigens were analyzed
      by conventional microcytotoxicity assays in these patients and 176 healthy
      control subjects. RESULTS: In class I antigens, B54 antigen significantly
      increased in the patient group (antigen frequency = 29.3%, relative risk = 3.23,
      corrected P value = .037) compared with normal control group (antigen frequency =
      11.4%). For class II antigens, no antigens were significantly increased.
      CONCLUSION: These data indicate that certain genetic factors play a role in the
      etiology of chronic sinusitis.

PMID- 10890779
TI  - Evidence for laryngeal paralysis in cricoarytenoid joint arthritis.
AB  - OBJECTIVE/HYPOTHESIS: To demonstrate denervation atrophy of laryngeal muscles in
      a case of gout involving the cricoarytenoid joint. METHODS: The posterior
      cricoarytenoid (PCA) and arytenoideus (A) muscles from a 72-year-old man with
      extensive gout were compared with those from a normal adult larynx (age and sex
      unknown) using stereologic techniques for changes in muscle composition and fiber
      diameter. RESULTS: The PCA and A muscles in the gout specimen contained changes
      Indicative of muscle degeneration. In the PCA the volume fraction (VF) of intact
      muscle was 0.30, of degenerating muscle 0.13, and of fat 0.16. A normal PCA had a
      VF for intact muscle of 0.64 and 0 for degenerating muscle and fat. Similar
      changes were seen in the gout A muscle but were not measured. Muscle fiber
      diameters in the gout PCA (1,024 fibers) showed a significantly higher atrophy
      and hypertrophy factor than the normal PCA (1,255 fibers). The variability
      coefficient in the gout PCA (487) was almost double that in the normal PCA (290).
      Although muscle fiber diameters were not measured in the A muscle in gout,
      variability in fiber size was seen. CONCLUSIONS: The pattern and magnitude of
      muscle fiber degeneration in the PCA and A muscles from a larynx with gout
      fixation of the cricoarytenoid joint indicate neural degeneration. Since similar
      changes were not found in the thyroarytenoid (TA) and lateral cricoarytenoid
      (LCA), the neuropathy is selective for the posterior branch of the recurrent
      laryngeal nerve. This neuropathy is likely responsible for vocal cord adduction
      (stridor) and incomplete closure of the posterior commissure (aspiration)
      associated with acute cricoarytenoid arthritis. In chronic cricoarytenoid joint
      arthritis, ankylosis of the joint space maintains the adducted cord position.

PMID- 10890780
TI  - Clinical experience with Gore-Tex for vocal fold medialization.
AB  - OBJECTIVES/HYPOTHESIS: Present clinical experience with vocal fold medialization
      under local anesthesia using a Gore-Tex implant. The procedure consists of
      placing the implant into a pocket formed by dissection of the inner perichondrium
      of the thyroid cartilage through a small window made in the thyroid ala. STUDY
      DESIGN: During 2 years, we used this technique preferentially in 13 of the 16
      cases of vocal fold medialization (three patients underwent Teflon injection
      because of a contraindication to local anesthesia). Follow-up was longer than 3
      months in 11 cases (mean, 13 mo). METHODS: Vocal result was analyzed by the means
      of perceptual analysis and by the measurement of jitter factor. Glottal leakage
      was evaluated perceptually using videolaryngoscopy, and oral airflow was measured
      during the production of a vowel. In cases with preoperative aspiration,
      videofluoroscopy was performed. RESULTS: Implantation was successful in all but
      one patient in whom extrusion of the implant material occurred. In the latter
      case, the implant was removed and the patient recuperated his preoperative voice
      without any other complication. In the 10 other cases, voice improvement assessed
      by perceptual and objective evaluation was satisfactory. CONCLUSIONS: Results
      compare favorably with those of endoscopic techniques using Teflon or collagen
      and laryngeal frame surgery techniques using silicone or cartilage. We conclude
      that Gore-Tex implantation is a simple, reproducible, and minimally invasive
      procedure for management of selected cases of vocal fold unilateral paralysis in
      the abductory position.

PMID- 10890781
TI  - Clinical evolution of laryngeal granulomas: treatment and prognosis.
AB  - OBJECTIVE/HYPOTHESIS: To study the response to treatment by patients with
      granulomas not related to surgery, considering their respective causes. METHODS:
      Retrospective study of larynx granulomas seen at the Instituto da Laringe (Sao
      Paulo, Brazil) from June 1996, totaling 66 patients, being 20 (30,3%) diagnosed
      with gastroesophageal reflux syndrome, 22 (33,3%) due to vocal abuse, 15 (22,7%)
      to postorotracheal intubation, and 9 (13,6%) of idiopathic cause. FINDINGS: Of
      the 66 patients diagnosed, 10 did not start the treatment, with only 56 being
      analyzed, 6 of whom later abandoned the treatment. The cause-oriented treatment
      showed 100% control in postintubation granulomas. In the cases of reflux and
      vocal abuse, the success rates when considering only the cause were 75% and
      87.5%, respectively. In the cases of undefined cause, all were subjected to
      surgical removal with or without clinical or speech-therapy treatment; we
      attained only a 37.5% success rate in the first trial. Of these, after various
      unsuccessful rescue treatments, three which were treated with botulinum toxin
      type A had 100% resolution. The recurrence percentage varied according to the
      cause, being nonexistent in the postintubation cases, 21.4% in patients with
      reflux esophagitis, 35.2% in vocal abuse, and 62.5% in those of idiopathic
      etiology. CONCLUSION: Of the laryngeal granulomas, the best prognoses were given
      by the postintubation ones, whereas the worst were those of undefined cause.
      Those ascribed to gastroesophageal reflux and vocal abuse have a high resolution
      rate, although some cases need rescue procedures.

PMID- 10890782
TI  - Differentiation of spasmodic and psychogenic dysphonias with phonoscopic
      evaluation.
AB  - OBJECTIVES: Identify laryngeal behaviors that differentiate patients with
      spasmodic dysphonia and patients with psychogenic dysphonia. STUDY DESIGN:
      Retrospective review of patients evaluated over a 3-year period with a diagnosis
      of either spasmodic or psychogenic dysphonia. Videotaped phonoscopic (laryngeal
      imaging) examinations of all noted aberrant behaviors were examined. Tally
      behaviors according to each subject group. METHODS: Three examiners unfamiliar
      with patients' previous diagnoses reviewed videotaped studies. Aberrant behaviors
      were noted and each patient was assigned to spasmodic or psychogenic dysphonia
      group. Agreement among examiners and agreement with previous diagnoses was
      established. RESULTS: Six abnormal behaviors were noted, including tremor,
      hyperadduction, false fold constriction, sphincteric constriction, hyperabduction
      and paradoxical movements of the true and false folds. Percentage of patients in
      each group with each behavior was determined. CONCLUSIONS: Individual behaviors
      did not generally appear to differentiate the two groups; however, patterns of
      behaviors did, and may be of considerable value in differentiating spasmodic and
      psychogenic dysphonias.

PMID- 10890784
TI  - Effect of harvesting autogenous laryngeal cartilage for laryngotracheal
      reconstruction on laryngeal growth and support.
AB  - OBJECTIVE: Determine the effect of harvesting autogenous thyroid cartilage on
      subsequent laryngeal growth and stability in a kitten model. STUDY DESIGN:
      Prospective controlled trial in animals. METHODS: Seventeen kittens were divided
      into three groups. Group one (n = 5) included kittens that underwent a unilateral
      thyroid cartilage resection. Group two (n = 5) included kittens that underwent a
      bilateral cartilage resection. Group three (n = 7) comprised kittens that did not
      undergo any surgical procedure (controls). All animals underwent endoscopic
      examination followed by the surgical procedure designated for that group. Kittens
      were then assessed daily for 2.5 months. At the end of that period the now
      "adolescent" cats were examined endoscopically then euthanized. The larynx was
      removed for gross and histopathologic analysis. RESULTS: All kittens tolerated
      the surgical procedure without airway compromise. Subsequent endoscopic
      examination 2.5 months after surgery revealed normal vocal cord function.
      Measurements of the true vocal cord and aryepiglottic and subglottic diameter did
      not differ significantly (one-way analysis of variance, P = .05) with respect to
      the side or the group. Histopathologic evaluation of the laryngeal sections
      indicated a patent airway, stable and viable thyroid cartilage, and no evidence
      of cartilaginous regrowth. CONCLUSIONS: The removal of unilateral and bilateral
      superior thyroid alar cartilage can be performed in kittens without postoperative
      respiratory or wound problems. The harvesting of autogenous thyroid cartilage has
      no apparent effect on subsequent laryngeal growth and stability in a kitten
      model.

PMID- 10890783
TI  - A management strategy for vocal process granulomas.
AB  - OBJECTIVES/HYPOTHESIS: Review the roles of aggressive gastroesophageal reflux
      management and speech therapy in the treatment of patients with vocal process
      granulomas. Describe and assess our investigation and management protocol. STUDY
      DESIGN: Retrospective review of 55 patients with 61 vocal granulomas treated
      according to a standard protocol at the Sydney Voice Clinic. Comparison with
      previous published series and review of the relevant literature pertaining to
      granulomas and to reflux. Description of laryngopharyngeal reflux grading,
      investigative modalities, and treatment regimen. METHODS: Case notes were
      reviewed and tabulated for age, sex, diagnosis, predisposing factors for
      granuloma formation, grade of laryngopharyngeal reflux, investigations,
      treatment, resolution, and recurrence. All patients were followed up for at least
      12 months after resolution. RESULTS: Fourteen of the 61 granulomas occurred after
      intubation. Ten patients were professional voice users. Our assessment of the 55
      granuloma patients revealed an incidence of 76% of gastroesophageal reflux
      disease in patients with and without known vocal fold trauma. There was a 50%
      recurrence rate following surgical excision. However, aggressive antireflux
      therapy, lifestyle modifications, and adjuvant speech therapy were successful in
      achieving resolution of most of the granulomas and preventing recurrence. In four
      patients, antireflux surgery was required and total resolution of the granulomas
      followed. CONCLUSIONS: Vocal process granulomas have perplexed laryngologists
      with their indeterminate pathogenesis and tendency to recur. Multiple surgical
      excisions and a variety of combined medical regimens have been used to treat
      granulomas with variable success. Recurrence after excision commonly occurs as
      the underlying causative factors have not been appropriately managed and may re
      establish the chronic inflammatory process. We found acid reflux to be a common
      factor in the majority of our patients with granulomas. Therefore treatment
      should focus on managing both reflux and any functional voice disease or
      disorder. The only indications for laryngeal surgery are to resolve diagnostic
      doubt or to treat acute airway compromise. Based on results, we suggest an
      algorithm for the investigation and management of vocal process granulomas
      founded on appropriate antireflux and speech therapy.

PMID- 10890785
TI  - Vascular anomalies causing symptomatic tracheobronchial compression.
AB  - OBJECTIVES/HYPOTHESIS: To review the clinical presentation and diagnostic
      evaluation of patients with symptomatic congenital vascular anomalies causing
      tracheobronchial compression and to establish the short- and long-term results of
      surgical intervention with respect to postoperative complications, persistent
      symptoms, and ventilator and tracheostomy dependence. STUDY DESIGN: Retrospective
      review. METHODS: Chart review and telephone follow-up. RESULTS: Between 1987 and
      1996, 35 children underwent surgical intervention to relieve symptomatic
      tracheobronchial compression resulting from a congenital vascular anomaly.
      Historically, the onset of symptoms occurs within the first months of life;
      however, only 12 (34%) of patients were diagnosed by 6 months of age and 13 (37%)
      were diagnosed at greater than 1 year of age. Excluding anomalous innominate
      artery, chest radiography or barium swallow was suggestive of a congenital
      vascular anomaly in 30 (94%) of the patients. Magnetic resonance imaging
      correctly delineated the anatomy of the vascular anomaly in 29 patients.
      Bronchoscopy was diagnostic in all three patients with anomalous innominate
      arteries causing tracheal compression. Postoperative follow-up was obtained in 32
      (91%) of patients; 25 (78%) of these were asymptomatic at the time of their most
      recent examination. The remaining patients had persistent stridor, recurrent
      respiratory tract infections, and/or chronic cough. In all three patients who
      underwent postoperative bronchoscopy for persistent symptoms, tracheomalacia was
      demonstrated in the region of previous compression. CONCLUSIONS: Tracheobronchial
      compression from congenital vascular anomalies is a rare but treatable cause of
      respiratory symptoms. Early diagnosis requires a prompt, thorough clinical and
      radiologic evaluation. Surgery affords excellent long-term resolution of
      symptoms.

PMID- 10890786
TI  - Isolated nasalis muscle reconstruction in secondary unilateral cleft lip nasal
      reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: Reconstruction of the nasalis muscle in the unilateral
      cleft lip nasal deformity improves surgical results. STUDY DESIGN: A
      retrospective analysis of a series of 112 consecutive procedures. METHODS: Chart
      review and analysis of standardized preoperative and postoperative clinical
      photographs. RESULTS: Patients treated with this technique had improved contour
      of the alar base compared with historical controls. CONCLUSION: Nasalis muscle
      reconstruction should be considered in the repair of the moderate to severe
      unilateral cleft nose deformity.

PMID- 10890787
TI  - Illness and otological changes during upper respiratory virus infection.
AB  - OBJECTIVES: Upper respiratory virus infection is associated with the expression
      of symptoms and signs of illness, and with the development of complications in
      anatomically contiguous structures. In most epidemiological studies, the
      frequency of the various complications is expressed as a fraction of the total
      population judged to be ill by report, signs, or symptoms. Because not all
      infected subjects become ill and because infected non-ill subjects may develop
      complications, such risk estimates could be inaccurate. The objective of this
      study was to estimate the magnitude of the presentation bias during controlled,
      experimental infections. STUDY DESIGN: This was a prospective, experimental study
      of the relationship between illness and otological complications during
      experimental upper respiratory virus infection in 316 adult volunteers. METHODS:
      The data for illness and for abnormal middle ear underpressure in adult (18-54 y)
      volunteers experimentally infected with one of three viruses (rhinovirus type 39,
      rhinovirus strain hanks, influenza A virus) were analyzed and expressed as the
      relative frequencies of infected subjects reporting illness, developing abnormal
      middle ear pressure, and developing abnormal middle ear pressure in the absence
      of illness. RESULTS: For all three viruses, illness was documented in
      approximately 50% of the infected subjects. While the frequency of persons
      developing abnormal middle ear underpressure was greater in the infected-ill
      subjects, approximately one third of all infected subjects developing that
      complication did not report illness. CONCLUSIONS: These results support a large
      presentation bias in epidemiological surveys of viral upper respiratory
      infections, and infer that those surveys underestimate the true frequency of
      complications resulting from such infections.

PMID- 10890788
TI  - Expression of gamma-aminobutyric acid(A) receptor subunits in the vestibular
      system.
AB  - OBJECTIVES: Profile the expression of genes encoding GABAA receptor subunits in
      the vestibular end organs of a rat. MATERIALS AND METHODS: Using a combination of
      reverse transcription followed by polymerase chain reaction (PCR) with gene
      specific primers, expression of mRNAs encoding 13 individual GABA(A) receptor
      subunits was examined. RESULTS: PCR amplification products representing subunit
      gene expression for alpha1-6, beta1-3, and gamma1-3, but not for delta, subunits
      were amplified, suggesting multiple molecular levels of regulation of vestibular
      GABA(A) receptor expression. Nucleotide sequencing confirmed the identity of rat
      vestibular end-organs subunit cDNAs. CONCLUSION: These results give the most
      direct evidence to date that GABAA receptors composed of the detected subunits
      are expressed in the mammalian vestibular system, giving new support to previous
      investigations implicating GABA as a vestibular neurotransmitter.

PMID- 10890789
TI  - Hearing loss with a mitochondrial gene mutation is highly prevalent in Japan.
AB  - OBJECTIVES/HYPOTHESIS: Mutations in the mitochondrial genome may predispose
      people to sensorineural hearing loss. An adenine to guanine point mutation in the
      tRNA(Leu(UUR)) gene at nucleotide 3,243 is one of the deaf-related mutations.
      This mutation is reported to be associated with 0.9% of diabetes mellitus
      patients. However, the prevalence of this mutation in hearing-impaired patients
      still remains unknown. The aim of this study was to determine the prevalence of
      this mutation among bilaterally sensorineural hearing-impaired patients in Japan.
      STUDY DESIGN: Retrospective survey of 100 patients with bilateral sensorineural
      hearing loss without any evident causes. METHODS: Mitochondrial DNA fragments
      from the patients were amplified by polymerase chain reaction, followed by a
      restriction enzyme fragment length polymorphism method. RESULTS: Three patients
      with this mutation were identified. Their clinical profiles were different from
      the category which had been considered as hearing loss caused by this
      mitochondrial gene mutation. CONCLUSIONS: The mutation is associated with
      approximately 3% of bilateral sensorineural hearing loss cases of unknown origin
      and is possibly distributed widely in sensorineural hearing-impaired patients in
      Japan.

PMID- 10890790
TI  - Endoscopic extraction of a metal foreign body from the maxillary sinus.

PMID- 10890791
TI  - Livial: a review of clinical studies.

PMID- 10890792
TI  - Livial: an economic appraisal.

PMID- 10890793
TI  - What is moderate drinking? Defining "drinks" and drinking levels.
AB  - Although the benefits and risks associated with moderate drinking have gained
      increasing attention in recent years from both researchers and the general
      public, no universal definition of moderate drinking exists. Most currently used
      definitions are based on a certain number of drinks consumed in a specific time
      period. Defining a "drink," however, also is difficult because alcoholic
      beverages can differ substantially in their alcohol content, even within the same
      beverage category (e.g., beer, wine, or distilled spirits). Because international
      differences in drink definitions also exist, comparing studies from different
      countries is difficult. The development of a universal definition of moderate
      drinking is hampered further by variations in the way alcohol consumption levels
      and drinking patterns are being assessed (i.e., the survey methods and assessment
      modes used). Despite these problems, definitions of moderate drinking and
      drinking guidelines have been developed in the United States and other countries.

PMID- 10890794
TI  - Moderate drinking and reduced risk of heart disease.
AB  - Although heavier drinkers are at increased risk for some heart diseases, moderate
      drinkers are at lower risk for the most common form of heart disease, coronary
      artery disease (CAD) than are either heavier drinkers or abstainers. This
      association has been demonstrated in large-scale epidemiological studies from
      many countries. Abstainers may share traits potentially related to CAD risk, such
      as psychological characteristics, dietary habits, and physical exercise patterns.
      However, evidence supports a direct protective effect of alcohol, even after data
      have been adjusted for the presence of these factors. The alcohol-CAD
      relationship is also independent of the hypothetically increased risk status
      among abstainers who stopped drinking for medical reasons. All alcoholic
      beverages protect against CAD, although some additional protection may be
      attributable to personal traits or drinking patterns among people who share some
      beverage preferences or to nonalcohol ingredients in specific beverages.
      Alcohol's protective effect may result from favorable alterations in blood
      chemistry and the prevention of clot formation in arteries that deliver blood to
      the heart muscle. Because CAD accounts for a large proportion of total mortality,
      the risk of death from all causes is slightly lower among moderate drinkers than
      among abstainers, but heavier drinkers are at considerably higher total mortality
      risk.

PMID- 10890795
TI  - Drinking moderately and pregnancy. Effects on child development.
AB  - Children exposed to moderate levels of alcohol during pregnancy show growth
      deficits and intellectual and behavioral problems similar to, although less
      severe than, those found in children with fetal alcohol syndrome. Research has
      begun to examine the extent to which these problems affect the child's ability to
      function on a day-to-day basis at school and with peers. Findings indicate that
      "moderate" drinking has much more impact on child development when the mother
      consumes several drinks in a single day than when she drinks the same quantity in
      doses of one to two drinks per day over several days.

PMID- 10890796
TI  - Preventing impaired driving.
AB  - Although moderate drinking does not necessarily increase a person's blood alcohol
      concentration (BAC) to the level at which driving is legally prohibited in the
      United States, any drinking can impair driving tasks. In addition to laws
      establishing lower legal BAC limits for drivers, legislative approaches for
      reducing alcohol-impaired driving include imposing sanctions for drinking and
      driving and restricting alcohol's availability.

PMID- 10890797
TI  - Alcohol and medication interactions.
AB  - Many medications can interact with alcohol, thereby altering the metabolism or
      effects of alcohol and/or the medication. Some of these interactions can occur
      even at moderate drinking levels and result in adverse health effects for the
      drinker. Two types of alcohol-medication interactions exist: (1) pharmacokinetic
      interactions, in which alcohol interferes with the metabolism of the medication,
      and (2) pharmacodynamic interactions, in which alcohol enhances the effects of
      the medication, particularly in the central nervous system (e.g., sedation).
      Pharmacokinetic interactions generally occur in the liver, where both alcohol and
      many medications are metabolized, frequently by the same enzymes. Numerous
      classes of prescription medications can interact with alcohol, including
      antibiotics, antidepressants, antihistamines, barbiturates, benzodiazepines,
      histamine H2 receptor antagonists, muscle relaxants, nonnarcotic pain medications
      and anti-inflammatory agents, opioids, and warfarin. In addition, many over-the
      counter and herbal medications can cause negative effects when taken with
      alcohol.

PMID- 10890798
TI  - Gender differences in moderate drinking effects.
AB  - Women appear to become more impaired than men after drinking equivalent amounts
      of alcohol, achieving higher blood alcohol concentrations even when doses are
      adjusted for body weight. This finding may be attributable in part to gender
      differences in total body water content. Men and women appear to eliminate
      approximately the same total amount of alcohol per unit body weight per hour.
      However, women seem to eliminate significantly more alcohol per unit of lean body
      mass per hour than men. Some studies report that women are more susceptible than
      men to alcohol-related impairment of cognitive performance, especially in tasks
      involving delayed memory or divided attention functions. Psychomotor performance
      impairment, however, does not appear to be affected by gender. This article
      provides an overview of alcohol metabolism (pharmacokinetics) and reviews recent
      studies on gender differences in alcohol absorption, distribution, elimination,
      and impairment. Speculation that gender differences in alcohol pharmacokinetics
      or alcohol-induced performance impairment may be caused by the menstrual cycle
      and variations in female sex hormones are discussed. It is concluded that the
      menstrual cycle is unlikely to influence alcohol pharmacokinetics.

PMID- 10890799
TI  - Alcoholism treatment in the United States. An overview.
AB  - On any given day, more than 700,000 people in the United States receive
      alcoholism treatment in either inpatient or outpatient settings. For many of
      those patients, detoxification--with or without pharmacotherapy--is the first
      step of treatment. The major behavioral approaches currently used in alcoholism
      treatment include cognitive-behavioral therapy, motivational enhancement therapy,
      and Alcoholics Anonymous (AA) or related 12-step programs. Clinical studies, such
      as the Project MATCH trial, have compared the effectiveness of these approaches.
      Overall, that study detected no significant differences among the three
      treatments in patient outcome, although certain treatment methodologies may be
      most appropriate for patients with certain characteristics. Pharmacotherapy with
      aversive or anticraving medications may supplement behavioral treatment
      approaches. Brief interventions that are delivered by primary health care
      providers also have been shown to reduce drinking levels, particularly in
      nondependent drinkers.

PMID- 10890800
TI  - Cognitive-behavioral coping-skills therapy for alcohol dependence. Current status
      and future directions.
AB  - Cognitive-behavioral coping-skills training (CBST) is an alcoholism treatment
      approach aimed at improving the patients' cognitive and behavioral skills for
      changing their drinking behavior. CBST encompasses a variety of approaches that
      despite their core similarities differ in duration, modality, content, and
      treatment setting. Numerous studies and reviews have ranked CBST among the most
      effective approaches for treating alcoholic patients. Nevertheless, a recent
      analysis of nine studies failed to identify specific CBST components that could
      account for the treatment's effectiveness. Furthermore, a similar analysis of 26
      studies suggested that CBST's superior effectiveness was limited to specific
      treatment contexts (i.e., when delivered as part of a comprehensive treatment
      program) and to specific patient subgroups (e.g., patients with less severe
      alcohol dependence). Several measures may help broaden CBST's focus and
      effectiveness, such as incorporating components of other treatment approaches.

PMID- 10890801
TI  - Motivation for change and alcoholism treatment.
AB  - Motivation plays an important role in alcoholism treatment by influencing
      patients to seek, complete, and comply with treatment as well as make successful
      long-term changes in their drinking. Both alcohol-abusing and alcohol-dependent
      people can be classified into different "stages of change" in terms of their
      readiness to alter their drinking behavior. Consequently, researchers have had to
      consider more seriously the role of motivation in the treatment of and recovery
      from substance abuse and to incorporate motivational enhancement strategies into
      treatment programs.

PMID- 10890802
TI  - Professional interventions that facilitate 12-step self-help group involvement.
AB  - Facilitating patients' involvement with 12-step self-help organizations, such as
      Alcoholics Anonymous (AA) and Narcotics Anonymous (NA), is often a goal of
      substance abuse treatment. Twelve-step-facilitation (TSF) interventions have been
      found to be more effective than comparison treatments in increasing patients' 12
      step group involvement and in promoting abstinence. Future TSF evaluation
      research should address the effectiveness of incorporating TSF interventions with
      cognitive-behavioral treatment methods, the relative impact of brief versus
      extended TSF interventions, and the cost-effectiveness and health care cost
      offset of TSF interventions within managed health care systems.

PMID- 10890804
TI  - Coping-skills training and cue-exposure therapy in the treatment of alcoholism.
AB  - Coping-skills training (CST) and cue-exposure treatment (CET) are two relatively
      new approaches in alcoholism treatment. With CST, the therapist tries to
      strengthen the patient's skills in coping with situations associated with a high
      risk of drinking. These skills can be specific to certain high-risk situations or
      involve general social skills. Specific CST treatment approaches include relapse
      prevention training, social or communication skills training, urge-specific
      coping-skills training, and cognitive-behavioral mood management training.
      Several studies have shown that CST can be more effective than comparison
      treatments in improving the outcome (e.g., the frequency and severity of
      relapses) of alcoholic patients. CET exposes the patient to alcohol-related cues
      (e.g., the sight or smell of alcohol), thereby allowing the patient to practice
      responses to such cues in real-life situations. In addition, CET teaches a
      variety of coping skills for dealing with urges caused by such cues. Few studies
      have examined the effectiveness of CET, but the existing results demonstrate
      favorable treatment outcomes (e.g., reduced drinking severity).

PMID- 10890803
TI  - Medications to treat alcoholism.
AB  - Advances in neurobiology support the development of medications to treat
      alcoholism by modifying the activity of specific chemical messengers (i.e.,
      neurotransmitters) in the brain. Among the most promising new medications is
      acamprosate, which appears to decrease the intensity of craving after a person
      has stopped drinking. Naltrexone (ReVia) has been shown to decrease alcohol
      consumption, although its practical effectiveness may be compromised by poor
      patient compliance and other factors. Ondansetron shows promise for decreasing
      drinking and increasing abstinence rates among early onset alcoholics, who
      respond poorly to psychosocial treatment alone. Researchers are investigating
      whether the use of specific medications in combination can further enhance their
      effectiveness. Additional research is needed to determine how medications
      interact with different psychosocial factors and treatments.

PMID- 10890805
TI  - The community-reinforcement approach.
AB  - The community-reinforcement approach (CRA) is an alcoholism treatment approach
      that aims to achieve abstinence by eliminating positive reinforcement for
      drinking and enhancing positive reinforcement for sobriety. CRA integrates
      several treatment components, including building the client's motivation to quit
      drinking, helping the client initiate sobriety, analyzing the client's drinking
      pattern, increasing positive reinforcement, learning new coping behaviors, and
      involving significant others in the recovery process. These components can be
      adjusted to the individual client's needs to achieve optimal treatment outcome.
      In addition, treatment outcome can be influenced by factors such as therapist
      style and initial treatment intensity. Several studies have provided evidence for
      CRA's effectiveness in achieving abstinence. Furthermore, CRA has been
      successfully integrated with a variety of other treatment approaches, such as
      family therapy and motivational interviewing, and has been tested in the
      treatment of other drug abuse.

PMID- 10890806
TI  - Contingency management. Incentives for sobriety.
AB  - Contingency management (CM), the systematic reinforcement of desired behaviors
      and the withholding of reinforcement or punishment of undesired behaviors, is an
      effective strategy in the treatment of alcohol and other drug (AOD) use
      disorders. Animal research provides the conceptual basis for using CM in AOD
      abuse treatment, and human studies have demonstrated the effectiveness of CM
      interventions in reducing AOD use; improving treatment attendance; and
      reinforcing other treatment goals, such as complying with a medication regimen or
      obtaining employment.

PMID- 10890807
TI  - Brief intervention in primary care settings. A primary treatment method for at
      risk, problem, and dependent drinkers.
AB  - Primary health care providers identify and treat many patients who are at risk
      for or are already experiencing alcohol-related problems. Brief interventions-
      counseling delivered by primary care providers in the context of several standard
      office visits--can be a successful treatment approach for many of these patients.
      Numerous trials involving a variety of patient populations have indicated that
      brief interventions can reduce patients' drinking levels, regardless of the
      patients' ages and gender. In clinical practice, brief interventions can help
      reduce the drinking levels of nondependent drinkers who drink more than the
      recommended limits, facilitate therapy and abstinence in patients receiving
      pharmacotherapy, and enhance the effectiveness of assessment and treatment
      referral in patients who do not respond to brief interventions alone. Despite the
      evidence for their usefulness, however, brief interventions for alcohol-related
      problems have not yet been widely implemented in primary care settings.

PMID- 10890808
TI  - Treating problem drinking.
AB  - Recent data suggest that most people experiencing alcohol problems have problems
      of mild to moderate severity. Relative to alcoholics, these drinkers have a
      shorter problem-drinking history, greater social and economic stability, and
      greater personal resources. This article describes a cognitive-behavioral
      treatment approach designed specifically for problem drinkers with low levels of
      physical dependence on alcohol who choose to reduce their drinking. After
      describing various drinking-reduction techniques, the article reviews empirical
      evidence for drinking-reduction training. The increasing availability of drinking
      reduction interventions holds considerable promise for reducing alcohol-related
      dysfunction among problem drinkers.

PMID- 10890809
TI  - Diagnosis and treatment of alcohol-dependent patients with comorbid psychiatric
      disorders.
AB  - Psychiatric disorders occur more often among alcoholics than among the general
      population. The psychiatric disorders that alcoholics most frequently experience
      include mood disorders (e.g., depression), anxiety disorders, and antisocial
      personality disorder. The evaluation of psychiatric symptoms in alcoholic
      patients is complicated by the multiple relationships that exist among heavy
      drinking, psychiatric symptoms, and personality factors. For example, alcoholics
      with co-occurring depression may be at greater risk of psychosocial problems,
      relapse, and suicide. Conversely, heavy drinking may produce or worsen symptoms
      of depression or anxiety. Although clinical experience provides general guidance
      for treating these patients, further research is needed to develop effective
      psychosocial and pharmacological therapies aimed at specific combinations of
      psychiatric and addictive disorders.

PMID- 10890810
TI  - Relapse prevention. An overview of Marlatt's cognitive-behavioral model.
AB  - Relapse prevention (RP) is an important component of alcoholism treatment. The RP
      model proposed by Marlatt and Gordon suggests that both immediate determinants
      (e.g., high-risk situations, coping skills, outcome expectancies, and the
      abstinence violation effect) and covert antecedents (e.g., lifestyle factors and
      urges and cravings) can contribute to relapse. The RP model also incorporates
      numerous specific and global intervention strategies that allow therapist and
      client to address each step of the relapse process. Specific interventions
      include identifying specific high-risk situations for each client and enhancing
      the client's skills for coping with those situations, increasing the client's
      self-efficacy, eliminating myths regarding alcohol's effects, managing lapses,
      and restructuring the client's perceptions of the relapse process. Global
      strategies comprise balancing the client's lifestyle and helping him or her
      develop positive addictions, employing stimulus control techniques and urge
      management techniques, and developing relapse road maps. Several studies have
      provided theoretical and practical support for the RP model.

PMID- 10890811
TI  - What is craving? Models and implications for treatment.
AB  - Although many alcoholics experience craving, researchers have not yet developed a
      common, valid definition of the phenomenon. Numerous models of the mechanisms
      underlying craving have been suggested, however. One of those models--the
      neuroadaptive model--suggests that the prolonged presence of alcohol induces
      changes in brain-cell function. In the absence of alcohol, those changes cause an
      imbalance in brain activity that results in craving. Furthermore, the adaptive
      changes generate memories of alcohol's pleasant effects that can be activated
      when alcohol-related environmental stimuli are encountered, even after prolonged
      abstinence, thereby leading to relapse. Similarly, stressful situations may
      trigger memories of the relief afforded by alcohol, which could also lead to
      relapse. Neurobiological and brain-imaging studies have identified numerous brain
      chemicals and brain regions that may be involved in craving. Psychiatric
      conditions that affect some of these brain regions, such as depression or
      anxiety, also may influence craving. A better understanding and more reliable
      assessment of craving may help clinicians tailor treatment to the specific needs
      of each patient, thereby reducing the risk of relapse.

PMID- 10890812
TI  - Inducing craving for alcohol in the laboratory.
AB  - Research on the mechanisms of craving often involves inducing craving in subjects
      in controlled settings. This article describes techniques that have been used to
      induce craving for alcohol, including (1) exposing subjects to actual alcoholic
      beverages, (2) exposing subjects to visual representations of alcoholic
      beverages, (3) manipulating the subjects' mood states, and (4) controlling
      environmental settings. The intensity of craving can be rated by the subjects
      themselves or can be assessed by clinicians through behavioral observations or
      the measurement of certain physiological responses. Success in inducing craving
      in the laboratory, however, has been inconsistent. Ultimately, researchers may
      need to monitor subjects' craving responses in actual environmental settings.

PMID- 10890813
TI  - Assessing craving for alcohol.
AB  - Craving for alcohol is common among alcohol-dependent people. Accordingly,
      measures to assess craving can play important roles in alcohol research as well
      as in alcoholism treatment. When developing or employing craving-assessment
      instruments, researchers and clinicians must consider numerous factors, such as
      the specific characteristics of craving to be evaluated, the instrument's
      psychometric properties, and the timeframe over which craving is assessed. The
      measures most commonly used for assessing craving in clinical settings are single
      item questionnaires, although several multi-item questionnaires also have been
      developed. Behavioral measures (e.g., amount of alcohol consumption or
      performance on cognitive tests) and psychophysiological measures (e.g., changes
      in salivation, respiration, or heart rate) are being used primarily in research
      settings. The assessment of craving can have numerous clinical benefits, such as
      helping the clinician to evaluate the severity of a patient's alcohol dependence,
      to select appropriate treatment approaches, and to monitor changes throughout a
      patient's treatment. The role of craving assessment in predicting treatment
      outcome, however, remains controversial.

PMID- 10890814
TI  - Functional imaging of craving.
AB  - To visualize brain activity associated with mental states, such as craving for
      alcohol and other drugs (AODs), researchers have begun to use functional imaging
      techniques. Three commonly used techniques are single photon emission computed
      tomography (SPECT), positron emission tomography (PET), and functional magnetic
      resonance imaging (fMRI). Studies using these three approaches have been reviewed
      in order to evaluate the validity of a proposed model of the brain regions
      involved in alcoholism and the craving for alcohol. This model suggests a central
      role for a connected group of brain regions that include the basal ganglia,
      thalamus, and orbital cortex. A study using SPECT technology in alcoholics,
      however, found altered brain activity in only some of those regions during
      craving. Additional studies in alcoholics, as well as cocaine users, identified
      several other brain regions whose activities appeared to change in response to
      craving. These studies have led to the development of a revised model of brain
      regions involved in craving for AODs. Numerous questions remain, however, that
      must be answered before the brain areas involved in craving can be identified
      conclusively.

PMID- 10890815
TI  - Approaching avoidance. A step essential to the understanding of craving.
AB  - Craving is only one component of the mental processes that influence drinking
      behavior. Alcohol-related cues (ARCs) can set in motion a dynamic competition
      between inclinations to approach drinking and inclinations to avoid drinking.
      Craving can thus be integrated into a comprehensive model of decision-making in
      which ambivalence or conflict is a key element. The relative strength of each
      component of the ARC reaction can fluctuate over time as well as in response to
      both subjective states and environmental circumstances. Simultaneously and
      independently evaluating these opposing responses puts clinicians in a better
      position to influence the relative weight that the patient assigns to the
      positive and negative outcomes of alcohol consumption.

PMID- 10890816
TI  - Medications and alcohol craving.
AB  - The use of medications as an adjunct to alcoholism treatment is based on the
      premise that craving and other manifestations of alcoholism are mediated by
      neurobiological mechanisms. Three of the four medications approved in the United
      States or Europe for treating alcoholism are reported to reduce craving; these
      include naltrexone (ReVia), acamprosate, and tiapride. The remaining medication,
      disulfiram (Antabuse), may also possess some anticraving activity. Additional
      medications that have been investigated include ritanserin, which has not been
      shown to decrease craving or drinking levels in humans, and ondansetron, which
      shows promise for treating early onset alcoholics, who generally respond poorly
      to psychosocial treatment alone. Use of anticraving medications in combination
      (e.g., naltrexone plus acamprosate) may enhance their effectiveness. Future
      studies should address such issues as optimal dosing regimens and the development
      of strategies to enhance patient compliance.

PMID- 10890817
TI  - Cognitive concepts of craving.
AB  - Traditional models of craving have been based primarily on the concept of
      classical conditioning. In recent years, however, researchers increasingly have
      introduced cognitive concepts, such as memory, expectancies, interpretation, and
      automatic behavior, into their conceptualizations of craving. These efforts have
      culminated in the development of four cognitive models of craving: cognitive
      labeling, outcome expectancy, dual-affect, and cognitive processing. The
      cognitive processing model posits that although many alcohol use behaviors have
      become automatized processes in the course of an alcoholic's drinking career,
      craving is a nonautomatic process that requires mental effort and is limited by a
      person's cognitive capacity. This model also implies that alcohol use and alcohol
      seeking behavior can occur in the absence of craving. In addition to introducing
      various new concepts and models into craving research, the cognitive sciences
      also offer well-established methodologies for testing these models and analyzing
      craving processes.

PMID- 10890818
TI  - Does urge to drink predict relapse after treatment?
AB  - The urge to drink, also often referred to as craving, is an emotional state in
      which a person is motivated to seek and use alcohol. In abstinent alcoholics,
      this urge may contribute to the risk of relapse. Researchers have developed
      several models--including the conditioned withdrawal model, conditioned
      appetitive motivational model, social learning model, and information-processing
      model--to describe the role of urges in relapse. Several studies have evaluated
      the role of urges in predicting alcoholism treatment outcome and relapse. Some
      findings indicate that the degree of urge an alcoholic experiences when
      confronted with a simulated high-risk situation at the end of alcoholism
      treatment can predict subsequent drinking. Other studies, however, show
      inconsistent results regarding the role of urges in predicting treatment outcome.
      Overall, the study results suggest that urges do not necessarily increase the
      risk of relapse but may actually protect some drinkers against further drinking.

PMID- 10890819
TI  - Animal models of craving: a roundtable discussion.
AB  - Five experts respected for their work in the development of animal models of
      alcohol craving offer their perspectives in a roundtable discussion format. The
      panel members discuss the various definitions and theories of alcohol craving and
      the benefits and limitations of using animal models to study alcohol craving in
      humans. Animal models have helped further the understanding of craving by
      providing information about behavior associated with craving. Animal models do
      have limitations, however. The fact that animals cannot "talk" about their
      feelings poses difficulties for researchers seeking to map an animal analog of
      craving onto the human experience.

PMID- 10890820
TI  - Understanding stress: characteristics and caveats.
AB  - Exposure to stressful situations is among the most common human experiences.
      These types of situations can range from unexpected calamities to routine daily
      annoyances. In response to stressors, a series of behavioral, neurochemical, and
      immunological changes occur that ought to serve in an adaptive capacity. However,
      if those systems become overly taxed, the organism may become vulnerable to
      pathology. Likewise, the biological changes, if sufficiently sustained, may
      themselves adversely affect the organism's well-being. Several factors may
      dictate an individual's response to environmental stressors, including
      characteristics of the stressor (i.e., type of stressor and its controllability,
      predictability, and chronicity); biological factors (i.e., age, gender, and
      genetics); and the subject's previous stressor history and early life
      experiences. Research on the physiological and psychological responses to
      different types of stressful stimuli is presented, focusing particularly on
      processes that may be relevant to the development of alcohol use disorders.
      Stressful events may profoundly influence the use of alcohol or other drugs
      (AODs). For example, the resumption of AOD use after a lengthy period of
      abstinence may reflect a person's attempt to self-medicate to attenuate the
      adverse psychological consequences of stressors (e.g., anxiety). Alternatively,
      stress may increase the reinforcing effects of AODs.

PMID- 10890821
TI  - Does drinking reduce stress?
AB  - For centuries, people have used alcohol to relieve stress--that is, the
      interpretation of an event as signaling harm, loss, or threat. The organism
      usually responds to stress with a variety of behavioral, biological, and
      cognitive changes. Alcohol consumption can result in a stress-response dampening
      (SRD) effect, which can be assessed using various measures. Numerous individual
      differences and situational factors help determine the extent to which a person
      experiences SRD after consuming alcohol. Individual differences include a family
      history of alcoholism, personality traits, extent of self-consciousness,
      cognitive functioning, and gender. Situational factors influencing alcohol's SRD
      effect include distractions during a stressful situation and the timing of
      drinking and stress. The attention-allocation model and the appraisal disruption
      model have been advanced to explain the influence of those situational factors.

PMID- 10890822
TI  - The role of uncontrollable trauma in the development of PTSD and alcohol
      addiction.
AB  - After a traumatic event, people often report using alcohol to relieve their
      symptoms of anxiety, irritability, and depression. Alcohol may relieve these
      symptoms because drinking compensates for deficiencies in endorphin activity
      following a traumatic experience. Within minutes of exposure to a traumatic event
      there is an increase in the level of endorphins in the brain. During the time of
      the trauma, endorphin levels remain elevated and help numb the emotional and
      physical pain of the trauma. However, after the trauma is over, endorphin levels
      gradually decrease and this may lead to a period of endorphin withdrawal that can
      last from hours to days. This period of endorphin withdrawal may produce
      emotional distress and contribute to other symptoms of posttraumatic stress
      disorder (PTSD). Because alcohol use increases endorphin activity, drinking
      following trauma may be used to compensate this endorphin withdrawal and thus
      avoid the associated emotional distress. This model has important implications
      for the treatment of PTSD and alcoholism.

PMID- 10890823
TI  - The role of stress in alcohol use, alcoholism treatment, and relapse.
AB  - Addiction to alcohol or other drugs (AODs) is a complex problem determined by
      multiple factors, including psychological and physiological components. Stress is
      considered a major contributor to the initiation and continuation of AOD use as
      well as to relapse. Many studies that have demonstrated an association between
      AOD use and stress have been unable to establish a causal relationship between
      the two. However, stress and the body's response to it most likely play a role in
      the vulnerability to initial AOD use, initiation of AOD abuse treatment, and
      relapse in recovering AOD users. This relationship probably is mediated, at least
      in part, by common neurochemical systems, such as the serotonin, dopamine, and
      opiate peptide systems, as well as the hypothalamic-pituitary-adrenal (HPA) axis.
      Further exploration of these connections should lead to important pharmacological
      developments in the prevention and treatment of AOD abuse. Studies indicate that
      treatment techniques which foster coping skills, problem-solving skills, and
      social support play a pivotal role in successful treatment. In the future,
      individualized treatment approaches that emphasize stress management strategies
      in those patients in whom a clear connection between stress and relapse exists
      will become particularly important.

PMID- 10890824
TI  - Alcohol, aging, and the stress response.
AB  - The body responds to stress through a hormone system called the hypothalamic
      pituitary-adrenal (HPA) axis. Stimulation of this system results in the secretion
      of stress hormones (i.e., glucocorticoids). Chronic excessive glucocorticoid
      secretion can have adverse health effects, such as Cushing's syndrome. Alcohol
      intoxication activates the HPA axis and results in elevated glucocorticoid
      levels. Ironically, elevated levels of these stress hormones may contribute to
      alcohol's pleasurable effects. With chronic alcohol consumption, however,
      tolerance may develop to alcohol's HPA axis-activating effects. Chronic alcohol
      consumption, as well as chronic glucocorticoid exposure, can result in premature
      and/or exaggerated aging. Furthermore, the aging process affects a person's
      sensitivity to alcohol and HPA axis function. Thus, a three-way interaction
      exists among alcohol consumption, HPA axis activity, and the aging process. The
      aging process may impair the HPA axis' ability to adapt to chronic alcohol
      exposure. Furthermore, HPA axis activation may contribute to the premature or
      exaggerated aging associated with chronic alcohol consumption.

PMID- 10890825
TI  - Work stress and alcohol use.
AB  - Employees who drink heavily or who abuse or are dependent on alcohol can
      undermine a workforce's overall health and productivity. To better understand the
      reasons behind employee abusive drinking and to develop more effective ways of
      preventing problem drinking in the workforce, researchers have developed a number
      of paradigms that guide their research. One such paradigm is the
      alienation/stress paradigm, which suggests that employee alcohol use may be a
      direct or indirect response to physical and psychosocial qualities of the work
      environment. Although in the alcohol literature, work alienation and work stress
      traditionally have been treated as separate paradigms, compelling reasons support
      subsuming the work-alienation paradigm under a general work-stress paradigm.
      Researchers have developed several models to explain the relationship between
      work stress and alcohol consumption: the simple cause-effect model, the mediation
      model, the moderation model, and the moderated mediation model. Of these, the
      moderated mediation model particularly stands out, because it simultaneously
      addresses the two fundamental issues of how and when work stressors are related
      to alcohol use. Recent research supports a relation of work-related stressors to
      elevated alcohol consumption and problem drinking. Future research should focus
      on the relation between work stressors and alcohol use among adolescents and
      young adults, because they are just entering the workforce and are the most
      likely to engage in heavy drinking. Longitudinal studies also are needed to
      better explain the relation between work stress and alcohol use.

PMID- 10890826
TI  - Can your children drive you to drink? Stress and parenting in adults interacting
      with children with ADHD.
AB  - Several publications in the psychological literature support the theory that
      children are a major source of stress for their parents. Not surprisingly,
      parents of children with behavior problems--particularly children with attention
      deficit hyperactivity disorder (ADHD)--experience highly elevated levels of daily
      child-rearing stresses. Children with ADHD disregard parental requests, commands,
      and rules; fight with siblings; disturb neighbors; and have frequent negative
      encounters with schoolteachers and principals. Although may investigations have
      dealt with parenting stress caused by disruptive children, only a handful of
      studies have addressed the question of how parents cope with this stress. Those
      findings are presented, including a series of studies assessing parental distress
      and alcohol consumption among parents of normal children and ADHD children after
      the parents interacted with either normal- or deviant-behaving children. Those
      studies strongly support the assumption that the deviant child behaviors that
      represent major chronic interpersonal stressors for parents of ADHD children are
      associated with increased parental alcohol consumption. Studies also have
      demonstrated that parenting hassles may result in increased alcohol consumption
      in parents of "normal" children. Given these findings, the stress associated with
      parenting and its influence on parental alcohol consumption should occupy a
      salient position among the variables that are examined in the study of stress and
      alcohol problems.

PMID- 10890827
TI  - A longitudinal study of stress, alcohol, and blood pressure in community-based
      samples of blacks and non-blacks.
AB  - Both alcohol use and stress appear to increase blood pressure. In addition,
      stress is associated with increased alcohol use. To investigate these
      relationships, researchers interviewed representative samples of the black and
      non-black adult household populations in Erie County, New York, in 1986, 1989,
      and 1993. The results support a causal relationship between stress and alcohol
      use and point to a number of factors that influence this relationship.
      Significant relationships between changes in alcohol use and blood pressure were
      also found. Although the researchers found little evidence for a direct effect of
      stress on blood pressure, stress related to family life, anxiety, and depression
      was associated with an increased risk for hypertension.

PMID- 10890828
TI  - Get overexposed for the new year.

PMID- 10890829
TI  - Advanced research systems' ATLANTES Care Management System.

PMID- 10890830
TI  - 1999--a very good year for URAC.

PMID- 10890831
TI  - Have a seat and then some: therapeutic positioning.

PMID- 10890832
TI  - Asthma case management outcomes.

PMID- 10890833
TI  - Integrated case management: the 21st century challenge for HMO case managers,
      Part II.

PMID- 10890834
TI  - Innovations in neonatal case management: an integrated, data-driven approach.
AB  - The intent of this article is to provide one company's perspective on the
      challenging and complex care management of the high-risk neonate. The strategies
      presented herein should enable and encourage case managers to implement an
      integrated management process for the frail neonatal population.

PMID- 10890835
TI  - The magic of music.

PMID- 10890836
TI  - Case management--a new marketing focus for tertiary medical centers.

PMID- 10890837
TI  - The paradigm switch for case managers. Some thoughts on the information
      technology challenges ahead.

PMID- 10890838
TI  - Population health management and the role of the case manager.

PMID- 10890839
TI  - CARF's case management standards.

PMID- 10890840
TI  - An opportunity for nursing students to author patient teaching materials.

PMID- 10890841
TI  - Student satisfaction with a Website designed for three nursing courses.
AB  - The website described was not designed to replace classroom teaching, but to
      serve as an additional tool for students attending a traditional course. Based on
      my experience and the data obtained from the evaluation questionnaire, the
      following points can be made: students are enthusiastic about the Internet and
      will access a web page that accompanies a particular course or courses a website
      can allow for objectives, not normally engendered by traditional methods, to be
      achieved. These may include, for instance, fostering a sense of community,
      providing new means of communication between professor and student and serving as
      a portal to the vast resources of the Internet. A single-theme website can
      effectively address the learning needs of students at different levels, in this
      case both undergraduate and graduate students A well-designed website can
      increase the visibility of the educational institution that sponsors it It is not
      easy to measure a website's effectiveness in helping students achieve traditional
      course objectives or its impact on student learning. The questionnaire results
      confirm students' satisfaction with the website and their belief that it was an
      important and useful learning tool. This is significant and positive. Future
      research is needed to measure the degree to which a website can increase learning
      in a particular area. The site required about 150 hours to construct and about 6
      8 hours per week to maintain. This is a considerable amount of faculty time.
      Although I cannot speak for others, I firmly believe that this is a worthwhile
      investment. The website is clearly appreciated by students, and it seems logical
      to conclude that it is fulfilling some learning needs that may not be met by
      other methods. In addition, it provides the educator with a new vehicle for
      communication. It is exhilarating to create with new formats and to use expertise
      in a given area to reach students, foster community, and establish a presence
      beyond the classroom. Creating and maintaining a web page is labor intensive, but
      it is, in my opinion, worth the effort. I strongly urge nurse educators to
      explore the possibilities of developing websites to accompany individual courses
      and to consider even more interactive web pages that include online discussion
      groups and provide space for posting student work. An active website needs
      frequent maintenance and updates. I recommend that academic administrators
      recognize web authoring as a valid and legitimate activity and provide nursing
      faculty with necessary support. This might include workshops on web authoring or
      Internet use, released time or credited time for initial website design, and
      credit allocation for site maintenance. The Internet is the most extensive
      collection of information available. As webmaster and pathophysiology expert, I
      am guiding my students; as a teacher, I am both assuming and recognizing a new
      role. As a teacher, I need to assume the responsibility for guiding students to
      worthwhile resources in the subject area. The website is a portal to the world,
      but a portal that I oversee.

PMID- 10890842
TI  - How do you cite a Web site?

PMID- 10890843
TI  - Ergonomics. If it hurts, fix it.

PMID- 10890844
TI  - Search engines on the information superhighway.

PMID- 10890845
TI  - The year 2000 (Y2K) problem. Nursing's call to action.

PMID- 10890846
TI  - A teleconsultation briefing. Another example of "ya gotta be there".

PMID- 10890847
TI  - Not so lovely spam.

PMID- 10890848
TI  - A computer spreadsheet approach to calculating course grades.

PMID- 10890849
TI  - Information for health. The new UK strategy.

PMID- 10890850
TI  - How a complete novice came to write a medical Web site. The St. Thomas' Hospital,
      London, Lupus Trust Web Site.

PMID- 10890851
TI  - Standardized nursing vocabularies and the perioperative nursing data set. Making
      clinical practice count.

PMID- 10890852
TI  - E-commerce: a quick guide to online shopping.

PMID- 10890853
TI  - Conducting nursing research via the Internet.

PMID- 10890854
TI  - VoIP and Internet telephony.

PMID- 10890855
TI  - Cases of exceptional language in mental retardation and Down syndrome:
      explanatory perspectives.
AB  - Recent studies of exceptional language development and functioning in mentally
      retarded people raise questions regarding basic issues in language disorders.
      These studies are summarised and their implications discussed. Possible reasons
      for the existence of such cases are examined including language training, general
      cognitive functioning, working memory, cerebral dominance, and deep-seated
      variation at brain level.

PMID- 10890856
TI  - Using augmentative communication with infants and young children with Down
      syndrome.
AB  - This paper reports the use of two forms of augmentative and alternative
      communication (AAC) with young children with Down syndrome: a program using
      signing (Makaton), and the COMPIC system of computerised pictographs. Children
      with Down syndrome are frequently reported to have difficulties in the area of
      language and communication, with relative strengths in visual and perceptual
      areas. This suggests possible benefits from the use of AAC systems to enhance
      language development. The paper discusses the use of AAC systems to assist young
      children with Down syndrome, and reports an experimental study of the use of such
      systems with an object naming task.

PMID- 10890857
TI  - Teaching basic skills to children with Down syndrome and developmental delays:
      the relative efficacy of interactive modeling with social rewards for benchmark
      achievements and passive observation.
AB  - In interventions attempting to remediate deficiencies in the skills repertoire of
      developmentally delayed children, no less than in medical interventions, it may
      be fairly said that less is more. That is, the instructor should intervene as
      little as possible both from the perspective of efficient instructional practice
      and from time allotment concerns which modern classrooms face. Evidence from this
      laboratory has indicated that in skills training for children with severe
      developmental delays the passive observation of a model demonstrating the target
      skill is more effective than interactive modeling involving hand-over-hand
      instruction with verbal prompting. We have considered the role of verbal
      prompting in interactive modeling and have found that prompts intended to provide
      typical social reinforcers are counterproductive (e.g., Biederman, Davey, Ryder,
      & Franchi, 1994). The present study examines the efficacy of hand-over-hand
      modeling with response-contingent verbal prompts. In such instruction, tasks are
      divided into identifiable sequential components, and the achievement of each
      component is marked by the delivery of some form of verbal prompt. In a within
      subjects design, children were trained in one skill with response-contingent
      verbal prompts and in a second skill with simple passive observation. A separate
      group of children were trained with less rigorous verbal prompting in one skill
      and with passive observation in a second. Consistent with previous research, we
      found that passive modeling was overall significantly more effective than hand
      over-hand modeling and moreover that passive modeling was significantly more
      effective than hand-over-hand modeling with response-contingent prompting. Our
      evidence therefore indicates that current classroom practice in training basic
      skills to children with severe developmental delays may require reassessment in
      that simple observation of modeled skills appears to be more effective than more
      labor-intensive instruction.

PMID- 10890858
TI  - Teenagers with Down syndrome study algebra in High School.
AB  - This paper deals with the adaptation of an algebra curriculum for two students
      with Down syndrome who were included in High School. Since the kindergarten, this
      boy and girl have been fully included in general education classes. This paper
      examines the rationale for this choice on an algebra program. The adaptation of
      this program was easy because all that was required was to shorten it and do some
      additional steps in teaching (a little bit more than in a remedial course). Also,
      visual prompts were provided to the students. The boy needed a calculator all the
      time. Both of the students learned to calculate algebraic expressions with
      parenthesis, with positive and negative numbers and even with powers. The boy was
      able to do algebraic sum of monomials. The girl performed expressions with
      fractions. They took written and oral tests at the same time as their classmates,
      but with different exercises or questions. The girl was able to do some mental
      arithmetic. Often she was more consistent and careful than her typical
      classmates. The boy had problems with the integration and he did not attend the
      school full time. The inclusion, even when it was not perfect, provided the
      motivation to teach and to learn. In both cases, the crucial point was the daily
      collaboration of the mathematics teacher with the special educator. Both of the
      students enjoyed the mathematics program, as many typical students do.
      Mathematics gave them the fulfilling emotion of succeeding!

PMID- 10890859
TI  - The effects of quality of life models on the development of research and practice
      in the field of Down syndrome.
AB  - The paper summarises the development of recent developments in relation to
      Quality of Life models in the field of intellectual disability. The information
      is applied to the development of professional practice and research. As examples,
      a series of research studies on Down syndrome are briefly described.

PMID- 10890860
TI  - Towards optimal mental health of persons with Down syndrome.
AB  - This paper outlines the risk of mental health disorders in adults with Down
      syndrome and considers the practical ways in which positive well-being can be
      promoted. It emphasises that prevention begins at birth and parents need to be
      alerted to positive child-rearing strategies from infancy.

PMID- 10890861
TI  - Conclusions of the 6th World Congress on Down syndrome. Madrid, 23rd-26th October
      1997.

PMID- 10890862
TI  - Mechanisms and comparison of anti-allergic efficacy of topical lodoxamide and
      cromolyn sodium treatment in vernal keratoconjunctivitis.
AB  - PURPOSE: To explore the mechanism of action of topical lodoxamide and cromolyn
      sodium treatment in vernal keratoconjunctivitis (VKC) and to compare the efficacy
      of these drugs to each other. DESIGN: Single-investigator, masked, randomized,
      clinical trial. PARTICIPANTS: Twenty male and 10 female patients between the ages
      of 6 and 19 years, who were diagnosed as having active VKC, were enrolled in this
      study. INTERVENTIONS: The patients were randomly divided into two equal groups
      (groups A and B). Group A patients received topical lodoxamide ophthalmic
      solution 0.1% (LOS); topical cromolyn sodium ophthalmic solution 4% (CSO) was
      prescribed to group B patients in a dose of two drops four times daily. MAIN
      OUTCOME MEASURES: The eye symptom severity scores and clinical signs of the
      patients were evaluated both in the pre- and post-treatment periods. In addition
      to the clinical data, conjunctival impression cytologic specimens were obtained
      from patients both before and after treatment. Impression cytologic specimens
      were stained using immunohistochemical methods to detect the percentages of
      CD4(+), CD8(+), CD45RA(+), and CD23(+) cells. Statistical analyses were performed
      within and between groups. RESULTS: The percentages of CD4(+) and CD23(+) cells
      in tear samples of patients in groups A and B were significantly higher in the
      pretreatment stage than post-treatment stage. In the post-treatment stage, group
      A patients had significantly lower CD4(+) and CD23(+) cell values compared with
      group B patients. Patient symptom scores and clinical signs were at a
      significantly lower level after treatment with either LOS or CSO in both groups A
      and B compared with their pretreatment values. Moreover, group A patients had
      significantly lower symptom scores and clinical signs than group B patients in
      the post-treatment stage. CONCLUSIONS: Clinical superiority of LOS over CSO may
      be linked to its greater effect on the CD4(+) cells, because CD4(+) cells plays a
      pivotal role in the pathogenesis of VKC.

PMID- 10890863
TI  - A call for glossaries in public health

PMID- 10890864
TI  - Do we learn our lessons from the population-based interventions?

PMID- 10890865
TI  - Freedom and quality of life.

PMID- 10890866
TI  - The health impact of German unification: still much to learn.

PMID- 10890867
TI  - Smoking and the compression of morbidity.
AB  - OBJECTIVE: To examine whether eliminating smoking will lead to a reduction in the
      number of years lived with disability (that is, absolute compression of
      morbidity). DESIGN: Multistate life table calculations based on the longitudinal
      GLOBE study (the Netherlands) combined with the Longitudinal Study of Aging
      (LSOA, United States of America). SETTING: the Netherlands. SUBJECTS: Dutch
      nationals aged 30-74 years living in the city of Eindhoven and surrounding
      municipalities (GLOBE) and United States citizens age 70 and over (LSOA). MAIN
      OUTCOME MEASURES: Life expectancy with and without disability and total life
      expectancy at ages 30 and 70. RESULTS: A non-smoking population on balance spends
      fewer years with disability than a mixed smoking-non-smoking population. Although
      non-smokers have lower mortality risks and thus are exposed to disability over a
      longer period of time, their lower incidence of disability and higher recovery
      from disability yield a net reduction of the length of time spent with disability
      (at age 30: -0.9 years in men and -1.1 years in women) and increases the length
      of time lived without disability (2.5 and 1.9 years, for men and women,
      respectively). These outcomes indicate that elimination of smoking will extend
      life and the period of disability free life, and will compress disability into a
      shorter period. CONCLUSIONS: Eliminating smoking will not only extend life and
      result in an increase in the number of years lived without disability, but will
      also compress disability into a shorter period. This implies that the commonly
      found trade off between longer life and a longer period with disability does not
      apply. Interventions to discourage smoking should receive high priority.

PMID- 10890868
TI  - Self rating of health is associated with stressful life events, social support
      and residency in East and West Berlin shortly after the fall of the wall.
AB  - STUDY OBJECTIVE: To compare the health status and factors influencing the health
      of populations that had previously lived under different political systems.
      DESIGN: Cross sectional health and social survey using postal interviews. The
      relation between self reported health and psychosocial factors (stressful life
      events, social support, education, health promoting life style and health
      endangering behaviour) was investigated. To determine East-West differences a
      logistic regression model including interaction terms was fitted. SETTING: East
      and West Berlin shortly after reunification 1991. PARTICIPANTS: Representative
      sample of 4430 Berlin residents aged 18 years and over (response rate 63%).
      RESULTS: Of all respondents, 15.4% rated their health as unsatisfactory.
      Residents of East Berlin rated their health more frequently as unsatisfactory
      than residents of West Berlin (Or(age adjusted)= 1.29, 95%CI 1.08, 1.52), these
      differences occurred predominantly in the over 60 years age group. Logistic
      regression showed significant independent effects of stressful life events,
      social support, education, and health promoting life style on self rated health.
      The effects of education and health promoting life style were observed to be more
      pronounced in the western part of Berlin. Old age and female sex showed a
      stronger association with unsatisfactory health status in the eastern part of
      Berlin. CONCLUSIONS: For subjects aged over 60 years there was evidence that
      living in the former East Berlin had an adverse effect on health compared with
      West Berlin. The impact of education and a health promoting lifestyle on self
      rated health seemed to be weaker in a former socialist society compared with that
      of a Western democracy. This study supports an "additive model" rather than a
      "buffering model" in explaining the effects of psychosocial factors on health.

PMID- 10890869
TI  - The epidemiology and experience of atopic eczema during childhood: a discussion
      paper on the implications of current knowledge for health care, public health
      policy and research.
AB  - Atopic eczema is a chronic skin condition affecting between 5% and 20% of
      children aged up to 11 years at one time or other. Research suggests that
      prevalence is increasing and various environmental factors have been implicated
      in the aetiology. While often seen to be a minor problem, research suggests that
      it can cause considerable disruption to the lives of children and their carers
      and involves significant cost for the family and health care systems. The current
      consensus is that the majority of cases of atopic eczema are most appropriately
      managed within primary care. However, management of the condition is problematic
      because diagnosis is often difficult. Consultations tend to focus on the physical
      aspects of the problems neglecting the psychosocial, while treatment remains
      mainly palliative and can be as diverse as the condition itself. More appropriate
      and effective primary care management and support for children with atopic eczema
      and their carers will only be developed if health professionals become more aware
      of the social context of the disease and the impact on the lives of those
      affected. Public health responses focusing on primary prevention are also needed.
      This paper reviews a diverse literature on the epidemiology of the condition, the
      way in which it affects the lives of children and their carers and the factors
      that shape their help seeking decisions. The aim is to contribute to a more
      substantial knowledge base for public health and primary care developments and to
      point to areas for future research

PMID- 10890870
TI  - Mortality after acute myocardial infarction is lower in metropolitan regions than
      in non-metropolitan regions.
AB  - STUDY OBJECTIVES: To compare in-hospital mortality for acute myocardial
      infarction (AMI) between metropolitan and non-metropolitan hospitals after
      adjustment for patients' severity; to examine the role of the use of effective
      cardiac medications in the possible mortality difference between these types of
      hospital. DESIGN: Retrospective cohort study. SETTING: 47 acute public hospitals
      in metropolitan and non-metropolitan areas of New South Wales, Australia, taking
      part in the Acute Cardiac Care Project based on medical record review. PATIENTS:
      1665 patients with principal discharge diagnosis of AMI from February to June
      1996. MAIN RESULTS: There was no difference in crude mortality rate (assessed as
      seven day mortality) between metropolitan and non-metropolitan hospitals (11.0%
      compared with 10.7% respectively, p=0.893). After adjustment for severity in a
      logistic regression model, the odds of death in non-metropolitan hospitals was
      significantly higher than in metropolitan hospitals (odds ratio = 1. 90; 95% CI
      1.21, 3.23). The addition of the use of effective cardiac medications to the
      model resulted in the difference between hospital type becoming non-significant
      (odds ratio=1.09; 95% CI 0.57, 2.07). CONCLUSIONS: In-hospital mortality in non
      metropolitan hospitals was higher than that in metropolitan hospitals, after
      adjustment for patients' severity. This might partly be explained by the
      difference in use of effective cardiac medications between hospital type.

PMID- 10890871
TI  - Relation of weight gain and weight loss on subsequent diabetes risk in overweight
      adults.
AB  - STUDY OBJECTIVE: To determine whether long term weight gain and weight loss are
      associated with subsequent risk of type 2 diabetes in overweight, non-diabetic
      adults. DESIGN: Prospective cohort. Baseline overweight was defined as BMI>/=27.3
      for women and BMI>/=27. 8 for men. Annual weight change (kg/year) over 10 years
      was calculated using measured weight at subjects' baseline and first follow up
      examinations. In the 10 years after measurement of weight change, incident cases
      of diabetes were ascertained by self report, hospital discharge records, and
      death certificates. SETTING: Community. PARTICIPANTS: 1929 overweight, non
      diabetic adults. MAIN RESULTS: Incident diabetes was ascertained in 251 subjects.
      Age adjusted cumulative incidence increased from 9.6% for BMI<29 to 26. 2% for
      BMI>/=37. Annual weight change over 10 years was higher in subjects who become
      diabetic compared with those who did not for all BMI<35. Relative to overweight
      people with stable weight, each kg of weight gained annually over 10 years was
      associated with a 49% increase in risk of developing diabetes in the subsequent
      10 years. Each kg of weight lost annually over 10 years was associated with a 33%
      lower risk of diabetes in the subsequent 10 years. CONCLUSIONS: Weight gain was
      associated with substantially increased risk of diabetes among overweight adults,
      and even modest weight loss was associated with significantly reduced diabetes
      risk. Minor weight reductions may have major beneficial effects on subsequent
      diabetes risk in overweight adults at high risk of developing diabetes.

PMID- 10890872
TI  - Capture-recapture methods to size alcohol related problems in a population.
AB  - STUDY OBJECTIVE: To investigate the utility of capture-recapture methods to
      estimate prevalence of subjects with alcohol related disorders using multiple
      incomplete lists. DESIGN: This was a cross sectional study of alcohol related
      disorders in a large community. SETTING: During 1997 identified cases with known
      alcohol related disorders were independently flagged by four sources (self help
      volunteering groups; psychiatric ambulatory; public alcohology service; hospital
      discharges). PATIENTS: 381 records were flagged, corresponding to 349 individual
      cases from a target population resident in a northern Italy area. MAIN RESULTS:
      The two sample capture-recapture estimates were clearly biased because of
      dependencies among sources. Estimates based on log-linear models showed prevalent
      counts ranged from 2297 (95% confidence intervals: 1524, 3794) to 2523 (95%
      confidence intervals: 1623, 4627) after adjustment for dependence among sources
      only or also for heterogeneity in catchability among age categories (< 50 and >/=
      50 years), respectively. CONCLUSIONS: The study suggests that capture-recapture
      is an appropriate approach for estimating prevalence of subjects with alcohol
      related problems who seek or need treatment and assistance when different lists
      of alcoholics can be obtained from different types of agencies involved with
      problematic use of alcohol. Critical factors are the complexity in case
      definition and the analysis of heterogeneity among people. Accurate estimates are
      needed to plan and evaluate public health interventions.

PMID- 10890873
TI  - The problem of accuracy in dietary surveys. Analysis of the over 65 UK National
      Diet and Nutrition Survey.
AB  - STUDY OBJECTIVE: To investigate the prevalence and nature of low energy reporting
      in a dietary survey of British adults over 65 years of age. DESIGN: Randomly
      selected cross sectional sample of 2060 British adults over 65 years. Four day
      weighed food diaries and questionnaires on health, lifestyle and socioeconomic
      characteristics. SETTING: Great Britain. PARTICIPANTS: 539 women and 558 men over
      65 years who were free living and completed four day food diaries. MAIN RESULTS:
      A high proportion of men and women were classified as low energy reporters
      (LERs). Reported consumption of full fat dairy products, sugar and sweet foods,
      and alcoholic drinks differed most between LERs and non-LERs. Among LERs,
      reported protein and starch intakes were higher, fat, sugar and alcohol intakes
      were lower. LERs of either sex were more likely to be obese, male LERs were also
      more likely to belong to the manual social classes. CONCLUSIONS: The high level
      of low energy reporting probably resulted from a coalescence of factors such as
      the weighed diary methodology and a reluctance to report consumption of unhealthy
      foods. The use of validatory biomarkers such as doubly labelled water needs to be
      more widespread.

PMID- 10890874
TI  - What is the "golden standard" for assessing population-based interventions?-
      problems of dilution bias.
AB  - OBJECTIVES: To identify different types of dilution bias in population-based
      interventions and to suggest measures for handling these methodological problems.
      DESIGN: Literature review plus analysis of data from a population-based
      intervention against cardiovascular disease in a Swedish municipality. MAIN
      RESULTS: The effects of an intervention on mortality and morbidity were much more
      diluted by non-intervening factors, dissemination to areas outside the
      intervention area, social diffusion, population mobility and time than by using
      intermediate outcome measures. CONCLUSIONS: Theoretically, changes in
      scientifically well documented risk factors, for example, intermediate outcome
      measures, should be preferred to using morbidity or mortality as outcome
      measures.

PMID- 10890875
TI  - Sources of influence on medical practice.
AB  - OBJECTIVES: To explore the opinion of general practitioners on the importance and
      legitimacy of sources of influence on medical practice. METHODS: General
      practitioners (n=723) assigned to Primary Care Teams (PCTs) in two Spanish
      regions were randomly selected to participate in this study. A self administered
      questionnaire was sent by mail and collected by hand. The dependent variable
      collected the opinion on different sources that exert influence on medical
      practice. Importance was measured with a 9 item scale while legitimacy was
      evaluated with 16 items measured with a 1 to 7 point Likert scale. RESULTS: The
      most important and legitimate sources of influence according to general
      practitioners were: training courses and scientific articles, designing self
      developed protocols and discussing with colleagues. The worst evaluated were:
      financial incentives and the role played by the pharmaceutical industry.
      CONCLUSIONS: The development of medical practice is determined by many factors,
      grouped around three big areas: organisational setting, professional system and
      social setting. The medical professional system is the one considered as being
      the most important and legitimate by general practitioners. Other strategies of
      influence, considered to be very important by the predominant management culture
      (financial incentives), are not considered to be so by general practitioners.
      These results, however, are not completely reliable as regards the real network
      of influences existing in medical practice, which reflect instead different
      "value systems".

PMID- 10890877
TI  - Obesity: trend in inequality.

PMID- 10890876
TI  - Inter-hospital variations in caesarean sections. A risk adjusted comparison in
      the Valencia public hospitals.
AB  - BACKGROUND: The aim of this study was to describe the variability in caesarean
      rates in the public hospitals in the Valencia Region, Spain, and to analyse the
      association between caesarean sections and clinical and extra-clinical factors.
      METHODS: Analysis of data contained in the Minimum Basic Data Set (MBDS) compiled
      for all births in 11 public hospitals in Valencia during 1994-1995 (n=36 819).
      Bivariate and multivariate analyses were used to evaluate the association between
      caesarean section rates and specific risk factors. The multivariate model was
      used to construct predictions about caesarean rates for each hospital, for
      comparison with rates observed. RESULTS: Caesarean rates were 17.6% (inter
      hospital range: 14.7% to 25.0%), with ample variability between hospitals in the
      diagnosis of maternal-fetal risk factors (particularly dystocia and fetal
      distress), and the indication for caesarean in the presence of these factors.
      Multivariate analysis showed that maternal-fetal risk factors correlated strongly
      with caesarean section, although extra-clinical factors, such as the day of the
      week, also correlated positively. After adjusting for the risk factors, the inter
      hospital variation in caesarean rates persisted. CONCLUSIONS: Although certain
      limitations (imprecision of some diagnoses and information biases in the MBDS)
      make it impossible to establish unequivocal conclusions, results show a high
      degree of variability among hospitals when opting for caesarean section. This
      variability cannot be justified by differences in obstetric risks.

PMID- 10890878
TI  - How accurate is self reported birth weight among the elderly?

PMID- 10890879
TI  - LXRalpha functions as a cAMP-responsive transcriptional regulator of gene
      expression.
AB  - LXRalpha is a member of a nuclear receptor superfamily that regulates
      transcription. LXRalpha forms a heterodimer with RXRalpha, another member of this
      family, to regulate the expression of cholesterol 7alpha-hydroxylase by means of
      binding to the DR4-type cis-element. Here, we describe a function for LXRalpha as
      a cAMP-responsive regulator of renin and c-myc gene transcriptions by the
      interaction with a specific cis-acting DNA element, CNRE (an overlapping cAMP
      response element and a negative response element). Our previous studies showed
      that renin gene expression is regulated by cAMP, at least partly, through the
      CNRE sequence in its 5'-flanking region. This sequence is also found in c-myc and
      several other genes. Based on our cloning results using the yeast one-hybrid
      system, we discovered that the mouse homologue of human LXRalpha binds to the
      CNRE and demonstrated that it binds as a monomer. To define the function of
      LXRalpha on gene expression, we transfected the renin-producing renal As4.1 cells
      with LXRalpha expression plasmid. Overexpression of LXRalpha in As4.1 cells
      confers cAMP inducibility to reporter constructs containing the renin CNRE. After
      stable transfection of LXRalpha, As4.1 cells show a cAMP-inducible up-regulation
      of renin mRNA expression. In parallel experiments, we demonstrated that LXRalpha
      can also bind to the homologous CNRE in the c-myc promoter. cAMP promotes
      transcription through c-myc/CNRE:LXRalpha interaction in LXRalpha transiently
      transfected cells and increases c-myc mRNA expression in stably transfected
      cells. Identification of LXRalpha as a cAMP-responsive nuclear modulator of renin
      and c-myc expression not only has cardiovascular significance but may have
      generalized implication in the regulation of gene transcription.

PMID- 10890880
TI  - Adenosine diphosphate glucose pyrophosphatase: A plastidial phosphodiesterase
      that prevents starch biosynthesis.
AB  - A distinct phosphodiesterasic activity (EC 3.1.4) was found in both mono- and
      dicotyledonous plants that catalyzes the hydrolytic breakdown of ADPglucose
      (ADPG) to produce equimolar amounts of glucose-1-phosphate and AMP. The enzyme
      responsible for this activity, referred to as ADPG pyrophosphatase (AGPPase), was
      purified over 1,100-fold from barley leaves and subjected to biochemical
      characterization. The calculated K(eq)' (modified equilibrium constant) value for
      the ADPG hydrolytic reaction at pH 7.0 and 25 degrees C is 110, and its standard
      state free-energy change value (DeltaG') is -2.9 kcal/mol (1 kcal = 4.18 kJ).
      Kinetic analyses showed that, although AGPPase can hydrolyze several low
      molecular weight phosphodiester bond-containing compounds, ADPG proved to be the
      best substrate (K(m) = 0.5 mM). P(i) and phosphorylated compounds such as 3
      phosphoglycerate, PP(i), ATP, ADP, NADP(+), and AMP are inhibitors of AGPPase.
      Subcellular localization studies revealed that AGPPase is localized exclusively
      in the plastidial compartment of cultured cells of sycamore (Acer pseudoplatanus
      L.), whereas it occurs both inside and outside the plastid in barley endosperm.
      In this paper, evidence is presented that shows that AGPPase, whose activity
      declines concomitantly with the accumulation of starch during development of sink
      organs, competes with starch synthase (ADPG:1,4-alpha-d-glucan 4-alpha-d
      glucosyltransferase; EC) for ADPG, thus markedly blocking the starch
      biosynthesis.

PMID- 10890881
TI  - Temperature and length scale dependence of hydrophobic effects and their possible
      implications for protein folding.
AB  - The Lum-Chandler-Weeks theory of hydrophobicity [Lum, K., Chandler, D. & Weeks,
      J. D. (1999) J. Phys. Chem. 103, 4570-4577] is applied to treat the temperature
      dependence of hydrophobic solvation in water. The application illustrates how the
      temperature dependence for hydrophobic surfaces extending less than 1 nm differs
      significantly from that for surfaces extending more than 1 nm. The latter is the
      result of water depletion, a collective effect, that appears at length scales of
      1 nm and larger. Because of the contrasting behaviors at small and large length
      scales, hydrophobicity by itself can explain the variable behavior of entropies
      of protein folding.

PMID- 10890882
TI  - Quantification of spread of cerebellar long-term depression with chemical two
      photon uncaging of glutamate.
AB  - Localized, chemical two-photon photolysis of caged glutamate was used to map the
      changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type
      glutamate receptors caused by long-term synaptic depression (LTD) in cerebellar
      Purkinje cells. LTD produced by pairing parallel fiber activity with
      depolarization was accompanied by a decline in the response of Purkinje cells to
      uncaged glutamate that accounted for both the time course and magnitude of LTD.
      This depression of glutamate responses was observed not only at the site of
      parallel fiber stimulation but also at more distant sites. The amount of LTD
      decreased with distance and was half-maximal 50 microm away from the site of
      parallel fiber activity. Estimation of the number of parallel fibers active
      during LTD induction indicates that LTD modified glutamate receptors not only at
      active synapses but also at 600 times as many inactive synapses on a single
      Purkinje cell. Therefore, both active and inactive parallel fiber synapses can
      undergo changes at a postsynaptic locus as a result of associative pre- and
      postsynaptic activity.

PMID- 10890883
TI  - Enhancement of induced disease resistance by simultaneous activation of
      salicylate- and jasmonate-dependent defense pathways in Arabidopsis thaliana.
AB  - The plant-signaling molecules salicylic acid (SA) and jasmonic acid (JA) play an
      important role in induced disease resistance pathways. Cross-talk between SA- and
      JA-dependent pathways can result in inhibition of JA-mediated defense responses.
      We investigated possible antagonistic interactions between the SA-dependent
      systemic acquired resistance (SAR) pathway, which is induced upon pathogen
      infection, and the JA-dependent induced systemic resistance (ISR) pathway, which
      is triggered by nonpathogenic Pseudomonas rhizobacteria. In Arabidopsis thaliana,
      SAR and ISR are effective against a broad spectrum of pathogens, including the
      foliar pathogen Pseudomonas syringae pv. tomato (Pst). Simultaneous activation of
      SAR and ISR resulted in an additive effect on the level of induced protection
      against Pst. In Arabidopsis genotypes that are blocked in either SAR or ISR, this
      additive effect was not evident. Moreover, induction of ISR did not affect the
      expression of the SAR marker gene PR-1 in plants expressing SAR. Together, these
      observations demonstrate that the SAR and the ISR pathway are compatible and that
      there is no significant cross-talk between these pathways. SAR and ISR both
      require the key regulatory protein NPR1. Plants expressing both types of induced
      resistance did not show elevated Npr1 transcript levels, indicating that the
      constitutive level of NPR1 is sufficient to facilitate simultaneous expression of
      SAR and ISR. These results suggest that the enhanced level of protection is
      established through parallel activation of complementary, NPR1-dependent defense
      responses that are both active against Pst. Therefore, combining SAR and ISR
      provides an attractive tool for the improvement of disease control.

PMID- 10890884
TI  - Excess "read-through" acetylcholinesterase attenuates but the "synaptic" variant
      intensifies neurodeterioration correlates.
AB  - Acute stress increases the risk for neurodegeneration, but the molecular signals
      regulating the shift from transient stress responses to progressive disease are
      not yet known. The "read-through" variant of acetylcholinesterase (AChE-R)
      accumulates in the mammalian brain under acute stress. Therefore, markers of
      neurodeterioration were examined in transgenic mice overexpressing either AChE-R
      or the "synaptic" AChE variant, AChE-S. Several observations demonstrate that
      excess AChE-R attenuates, whereas AChE-S intensifies, neurodeterioration. In the
      somatosensory cortex, AChE-S transgenics, but not AChE-R or control FVB/N mice,
      displayed a high density of curled neuronal processes indicative of
      hyperexcitation. In the hippocampus, AChE-S and control mice, but not AChE-R
      transgenics, presented progressive accumulation of clustered, heat shock protein
      70-immunopositive neuronal fragments and displayed a high incidence of reactive
      astrocytes. Our findings suggest that AChE-R serves as a modulator that may play
      a role in preventing the shift from transient, acute stress to progressive
      neurological disease.

PMID- 10890886
TI  - Mitochondria as ATP consumers: cellular treason in anoxia.
AB  - In anoxia, mitochondria change from being ATP producers to potentially powerful
      ATP consumers. This change occurs, because the mitochondrial F(1)F(0)-ATPase
      begins to hydrolyze ATP to avoid the collapse of the proton motive force. Species
      that can survive prolonged periods of O(2) lack must limit such ATP use;
      otherwise, this process would dominate glycolytic metabolism and threaten ATP
      delivery to essential ATP-consuming processes of the cell (e.g., ion-motive
      ATPases). There are two ways to limit ATP hydrolysis by the F(1)F(0)-ATPase,
      namely (i) reduction of the proton conductance of the mitochondrial inner
      membrane and (ii) inhibition of the enzyme. We assessed these two possibilities
      by using intact mitochondria isolated from the skeletal muscle of anoxia-tolerant
      frogs. Our results show that proton conductance is unaltered between normoxia and
      anoxia. However, ATP use by the F(1)F(0)-ATPase is limited in anoxia by a
      profound inhibition of the enzyme. Even so, ATP use by the F(1)F(0)-ATPase might
      account for approximately 9% of the ATP turnover in anoxic frog skeletal muscle.

PMID- 10890885
TI  - Phosphate is a specific signal for induction of osteopontin gene expression.
AB  - Osteopontin is a phosphorylated glycoprotein secreted to the mineralizing
      extracellular matrix by osteoblasts during bone development. It is believed to
      facilitate the attachment of osteoblasts and osteoclasts to the extracellular
      matrix, allowing them to perform their respective functions during osteogenesis.
      Several other functions have been suggested for this protein, and its up
      regulation is associated with various disease states related to calcification,
      including arterial plaque formation and the formation of kidney stones. Although
      expression of this gene has been demonstrated in multiple tissues, its regulation
      is not well understood. Our previous studies on the roles of the retinoblastoma
      protein (pRB) and p300/CBP in the regulation of osteoblast differentiation
      revealed a link between osteopontin induction and the synthesis of alkaline
      phosphatase. In this paper, we describe results specifically linking induction of
      osteopontin to the enzymatic activity of alkaline phosphatase in the medium,
      which results in the generation of free phosphate. This elevation of free
      phosphate in the medium is sufficient to signal induction of osteopontin RNA and
      protein. The strong and specific induction of osteopontin in direct response to
      increased phosphate levels provides a mechanism to explain how expression of this
      product is normally regulated in bone and suggests how it may become up-regulated
      in damaged tissue.

PMID- 10890887
TI  - A quantitative, high-throughput screen for protein stability.
AB  - In proteomic research, it is often necessary to screen a large number of
      polypeptides for the presence of stable structure. Described here is a technique
      (referred to as SUPREX, stability of unpurified proteins from rates of H/D
      exchange) for measuring the stability of proteins in a rapid, high-throughput
      fashion. The method uses hydrogen exchange to estimate the stability of microgram
      quantities of unpurified protein extracts by using matrix-assisted laser
      desorption/ionization MS. The stabilities of maltose binding protein and
      monomeric lambda repressor variants determined by SUPREX agree well with
      stability data obtained from conventional CD denaturation of purified protein.
      The method also can detect the change in stability caused by the binding of
      maltose to maltose binding protein. The results demonstrate the precision of the
      method over a wide range of stabilities.

PMID- 10890888
TI  - Transcription coupled repair of 8-oxoguanine in murine cells: the ogg1 protein is
      required for repair in nontranscribed sequences but not in transcribed sequences.
AB  - To assess the role of the Ogg1 DNA glycosylase in the transcription-coupled
      repair (TCR) of the mutagenic lesion, 7, 8-dihydro-8oxoguanine (8-OxoG), we have
      investigated the removal of this lesion in wild-type and ogg1(-/-) null mouse
      embryo fibroblast (MEF) cell lines. We used nonreplicating plasmids containing a
      single 8-OxoG.C base pair in a different assay that allowed us to study the
      removal of 8-OxoG located in a transcribed sequence (TS) or in a nontranscribed
      sequence (NTS). The results show that the removal of 8-OxoG in a wild-type MEF
      cell line is faster in the TS than in the NTS, indicating TCR of 8-OxoG in murine
      cells. In the homozygous ogg1(-/-) MEF cell line, 8-OxoG was not removed from the
      NTS whereas there was still efficient 8-OxoG repair in the TS. Expression of the
      mouse Ogg1 protein in the homozygous ogg1(-/-) cell line restored the ability to
      remove 8-OxoG in the NTS. Therefore, we have demonstrated that Ogg1 is essential
      for the repair of 8-OxoG in the NTS but is not required in the TS. These results
      indicate the existence of an Ogg1-independent pathway for the TCR of 8-OxoG in
      vivo.

PMID- 10890889
TI  - A repressible female-specific lethal genetic system for making transgenic insect
      strains suitable for a sterile-release program.
AB  - We have developed a tetracycline-repressible female-specific lethal genetic
      system in the vinegar fly Drosophila melanogaster. One component of the system is
      the tetracycline-controlled transactivator gene under the control of the fat body
      and female-specific transcription enhancer from the yolk protein 1 gene. The
      other component consists of the proapoptotic gene hid under the control of a
      tetracycline-responsive element. Males and females of a strain carrying both
      components are viable on medium supplemented with tetracycline, but only males
      survive on normal medium. A strain with such properties would be ideal for a
      sterile-insect release program, which is most effective when only males are
      released in the field.

PMID- 10890890
TI  - A male germ cell tumor-susceptibility-determining locus, pgct1, identified on
      murine chromosome 13.
AB  - Inbred 129 strain mice are predisposed to developing male germ cell tumors (GCTs)
      of the testes. The inherent genetic defects that underlie male GCT susceptibility
      in the 129 mouse strain are unknown. GCT incidence is increased in 129 strain
      males that lack functional p53 protein, and we have used this finding to
      facilitate the generation of panels of GCT-bearing intercross and backcross mice
      for genetic mapping analysis. A 129 strain locus, designated pgct1, that
      segregates with the male GCT phenotype has been identified on chromosome 13 near
      D13Mit188. This region of murine chromosome 13 may be syntenic to a portion of
      human chromosome 5q that is implicated in male GCT susceptibility in humans.

PMID- 10890891
TI  - Site-specific chemical modification with polyethylene glycol of recombinant
      immunotoxin anti-Tac(Fv)-PE38 (LMB-2) improves antitumor activity and reduces
      animal toxicity and immunogenicity.
AB  - Chemical modification of proteins with polyethylene glycol (PEGylation) can
      increase plasma half-lives, stability, and therapeutic potency. To make a
      PEGylated recombinant immunotoxin with improved therapeutic properties, we
      prepared a mutant of anti-Tac(Fv)-PE38 (LMB-2), a recombinant immunotoxin
      composed of a single-chain Fv fragment of the anti-human Tac monoclonal antibody
      to the IL-2 receptor alpha subunit fused to a 38-kDa fragment of Pseudomonas
      exotoxin. For site-specific PEGylation of LMB-2, one cysteine residue was
      introduced into the peptide connector (ASGCGPE) between the Fv and the toxin.
      This mutant LMB-2 (cys1-LMB-2), which retained full cytotoxic activity, was then
      site-specifically conjugated with 5 or 20 kDa of polyethylene glycol-maleimide.
      When compared with unmodified LMB-2, both PEGylated immunotoxins showed similar
      cytotoxic activities in vitro but superior stability at 37 degrees C in mouse
      serum, a 5- to 8-fold increase in plasma half-lives in mice, and a 3- to 4-fold
      increase in antitumor activity. This was accompanied by a substantial decrease in
      animal toxicity and immunogenicity. Site-specific PEGylation of recombinant
      immunotoxins may increase their therapeutic potency in humans.

PMID- 10890892
TI  - Fibroblast growth factors: an epigenetic mechanism of broad spectrum resistance
      to anticancer drugs.
AB  - Based on the observation that removal of tumors from metastatic organs reversed
      their chemoresistance, we hypothesized that chemoresistance is induced by
      extracellular factors in tumor-bearing organs. By comparing chemosensitivity and
      proteins in different tumors (primary vs. metastases) and different culture
      systems (tumor fragment histocultures vs. monolayer cultures derived from the
      same tumor), we found elevated levels of acidic (aFGF) and basic (bFGF)
      fibroblast growth factors in the conditioned medium (CM) of solid and metastatic
      tumors. These CM induced broad spectrum resistance to drugs with diverse
      structures and action mechanisms (paclitaxel, doxorubicin, 5-fluorouracil).
      Inhibition of bFGF by mAb and its removal by immunoprecipitation resulted in
      complete reversal of the CM-induced chemoresistance, whereas inhibition/removal
      of aFGF resulted in partial reversal. Using CM that had been depleted of aFGF
      and/or bFGF and subsequently reconstituted with respective human recombinant
      proteins, we found that bFGF but not aFGF induced chemoresistance whereas aFGF
      amplified the bFGF effect. aFGF and bFGF fully accounted for the CM effect,
      indicating these proteins as the underlying mechanism of the chemoresistance. The
      FGF-induced resistance was not due to reduced intracellular drug accumulation or
      altered cell proliferation. We further showed that an inhibitor of aFGF/bFGF
      (suramin) enhanced the in vitro and in vivo activity of chemotherapy, resulting
      in shrinkage and eradication of well established human lung metastases in mice
      without enhancing toxicity. These results indicate elevated levels of
      extracellular aFGF/bFGF as an epigenetic mechanism by which cancer cells elude
      cytotoxic insult by chemotherapy, and provide a basis for designing new treatment
      strategies.

PMID- 10890893
TI  - Crystal structure of the holliday junction DNA in complex with a single RuvA
      tetramer.
AB  - In the major pathway of homologous DNA recombination in prokaryotic cells, the
      Holliday junction intermediate is processed through its association with RuvA,
      RuvB, and RuvC proteins. Specific binding of the RuvA tetramer to the Holliday
      junction is required for the RuvB motor protein to be loaded onto the junction
      DNA, and the RuvAB complex drives the ATP-dependent branch migration. We solved
      the crystal structure of the Holliday junction bound to a single Escherichia coli
      RuvA tetramer at 3.1-A resolution. In this complex, one side of DNA is accessible
      for cleavage by RuvC resolvase at the junction center. The refined junction DNA
      structure revealed an open concave architecture with a four-fold symmetry. Each
      arm, with B-form DNA, in the Holliday junction is predominantly recognized in the
      minor groove through hydrogen bonds with two repeated helix-hairpin-helix motifs
      of each RuvA subunit. The local conformation near the crossover point, where two
      base pairs are disrupted, suggests a possible scheme for successive base pair
      rearrangements, which may account for smooth Holliday junction movement without
      segmental unwinding.

PMID- 10890894
TI  - An ethylene-induced cDNA encoding a lipase expressed at the onset of senescence.
AB  - A cDNA clone encoding a lipase (lipolytic acyl hydrolase) expressed at the onset
      of petal senescence has been isolated by screening a cDNA expression library
      prepared from carnation flowers (Dianthus caryophyllus). The cDNA contains the
      lipase consensus sequence, ITFAGHSLGA, and encodes a 447-amino acid polypeptide
      with a calculated molecular mass of 50.2 kDa that appears to be a cytosolic
      protein. Over-expression of the clone in Escherichia coli yielded a protein of
      the expected molecular weight that proved capable of deesterifying fatty acids
      from p-nitrophenylpalmitate, tri-linolein, soybean phospholipid, and Tween in
      both in vitro and in situ assays of enzyme activity. The abundance of the lipase
      mRNA increases just as carnation flowers begin to senesce, and expression of the
      gene is also induced by treatment with ethylene. Southern blot analyses of
      carnation genomic DNA have indicated that the lipase is a single copy gene. The
      lipase gene is also expressed in carnation leaves and is up-regulated when the
      leaves are treated with ethylene. Deesterification of membrane lipids and ensuing
      loss of membrane structural integrity are well established early events of plant
      senescence, and the expression pattern of this lipase gene together with the
      lipolytic activity of its cognate protein indicate that it plays a fundamentally
      central role in mediating the onset of senescence.

PMID- 10890895
TI  - Retinoic acid induces sodium/iodide symporter gene expression and radioiodide
      uptake in the MCF-7 breast cancer cell line.
AB  - The sodium/iodide symporter (NIS) stimulates iodide uptake in normal lactating
      breast, but is not known to be active in nonlactating breast or breast cancer. We
      studied NIS gene regulation and iodide uptake in MCF-7 cells, an estrogen
      receptor (ER)-positive human breast cancer cell line. All-trans retinoic acid
      (tRA) treatment stimulated iodide uptake in a time- and dose-dependent fashion up
      to approximately 9.4-fold above baseline. Stimulation with selective retinoid
      compounds indicated that the induction of iodide uptake was mediated by retinoic
      acid receptor. Treatment with tRA markedly stimulated NIS mRNA and immunoreactive
      protein ( approximately 68 kDa). tRA stimulated NIS gene transcription
      approximately 4-fold, as shown by nuclear run-on assay. No induction of iodide
      uptake was observed with RA treatment of an ER-negative human breast cancer cell
      line, MDA-MB 231, or a normal human breast cell line, MCF-12A. The iodide efflux
      rate of tRA-treated MCF-7 cells was slow (t(1/2) = 24 min), compared with that in
      FRTL-5 thyroid cells (t(1/2) = 3.9 min), favoring iodide retention in MCF-7
      cells. An in vitro clonogenic assay demonstrated selective cytotoxicity with
      (131)I after tRA stimulation of MCF-7 cells. tRA up-regulates NIS gene expression
      and iodide uptake in an ER-positive breast cancer cell line. Stimulation of
      radioiodide uptake after systemic retinoid treatment may be useful for diagnosis
      and treatment of some differentiated breast cancers.

PMID- 10890896
TI  - Inhibition of proteasomal degradation by the gly-Ala repeat of Epstein-Barr virus
      is influenced by the length of the repeat and the strength of the degradation
      signal.
AB  - The Gly-Ala repeat (GAr) of the Epstein-Barr virus nuclear antigen-1 is a
      transferable element that inhibits in cis ubiquitin/proteasome-dependent
      proteolysis. We have investigated this inhibitory activity by using green
      fluorescent protein-based reporters that have been targeted for proteolysis by N
      end rule or ubiquitin-fusion degradation signals, resulting in various degrees of
      destabilization. Degradation of the green fluorescent protein substrates was
      inhibited on insertion of a 25-aa GAr, but strongly destabilized reporters were
      protected only partially. Protection could be enhanced by increasing the length
      of the repeat. However, reporters containing the Ub-R and ubiquitin-fusion
      degradation signals were degraded even in the presence of a 239-aa GAr. In
      accordance, insertion of a powerful degradation signal relieved the blockade of
      proteasomal degradation in Epstein-Barr virus nuclear antigen-1. Our findings
      suggest that the turnover of natural substrates may be finely tuned by GAr-like
      sequences that counteract targeting signals for proteasomal destruction.

PMID- 10890897
TI  - Inositol hexakisphosphate is a physiological signal regulating the K+-inward
      rectifying conductance in guard cells.
AB  - (RS)-2-cis, 4-trans-abscisic acid (ABA), a naturally occurring plant stress
      hormone, elicited rapid agonist-specific changes in myo-inositol hexakisphosphate
      (InsP(6)) measured in intact guard cells of Solanum tuberosum (n = 5); these
      changes were not reproduced by (RS)-2-trans, 4-trans-abscisic acid, an inactive
      stereoisomer of ABA (n = 4). The electrophysiological effects of InsP(6) were
      assessed on both S. tuberosum (n = 14) and Vicia faba (n = 6) guard cell
      protoplasts. In both species, submicromolar concentrations of InsP(6), delivered
      through the patch electrode, mimicked the inhibitory effects of ABA and internal
      calcium (Ca(i)(2+)) on the inward rectifying K(+) current, I(K,in), in a dose
      dependent manner. Steady state block of I(K,in) by InsP(6) was reached much more
      quickly in Vicia (3 min at approximately 1 microM) than Solanum (20-30 min). The
      effects of InsP(6) on I(K,in) were specific to the myo-inositol isomer and were
      not elicited by other conformers of InsP(6) (e.g., scyllo- or neo-). Chelation of
      Ca(2+) by inclusion of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
      or EGTA in the patch pipette together with InsP(6) prevented the inhibition of
      I(K,in), suggesting that the effect is Ca(2+) dependent. InsP(6) was
      approximately 100-fold more potent than Ins(1,4,5)P(3) in modulating I(K,in).
      Thus ABA increases InsP(6) in guard cells, and InsP(6) is a potent Ca(2+)
      dependent inhibitor of I(K,in). Taken together, these results suggest that
      InsP(6) may play a major role in the physiological response of guard cells to
      ABA.

PMID- 10890898
TI  - Balancing transcriptional interference and initiation on the GAL7 promoter of
      Saccharomyces cerevisiae.
AB  - Transcriptional termination of the GAL10 gene in Saccharomyces cerevisiae depends
      on the efficiency of polyadenylation. Either cis mutations in the poly(A) signal
      or trans mutations of mRNA 3' end cleavage factors result in GAL10 read-through
      transcripts into the adjacent GAL7 gene and inactivation (occlusion) of the GAL7
      promoter. Herein, we present a molecular explanation of this transcriptional
      interference phenomenon. In vivo footprinting data reveal that GAL7 promoter
      occlusion is associated with the displacement of Gal4p transcription factors from
      the promoter. Interestingly, overexpression of Gal4p restores promoter occupancy,
      activates GAL7 expression, and rescues growth on the otherwise toxic galactose
      substrate. Our data therefore demonstrate a precise balance between
      transcriptional interference and initiation.

PMID- 10890899
TI  - Calcium release from the endoplasmic reticulum of higher plants elicited by the
      NADP metabolite nicotinic acid adenine dinucleotide phosphate.
AB  - Higher plants share with animals a responsiveness to the Ca(2+) mobilizing agents
      inositol 1,4,5-trisphosphate (InsP(3)) and cyclic ADP-ribose (cADPR). In this
      study, by using a vesicular (45)Ca(2+) flux assay, we demonstrate that microsomal
      vesicles from red beet and cauliflower also respond to nicotinic acid adenine
      dinucleotide phosphate (NAADP), a Ca(2+)-releasing molecule recently described in
      marine invertebrates. NAADP potently mobilizes Ca(2+) with a K(1/2) = 96 nM from
      microsomes of nonvacuolar origin in red beet. Analysis of sucrose gradient
      separated cauliflower microsomes revealed that the NAADP-sensitive Ca(2+) pool
      was derived from the endoplasmic reticulum. This exclusively nonvacuolar location
      of the NAADP-sensitive Ca(2+) pathway distinguishes it from the InsP(3)- and
      cADPR-gated pathways. Desensitization experiments revealed that homogenates
      derived from cauliflower tissue contained low levels of NAADP (125 pmol/mg) and
      were competent in NAADP synthesis when provided with the substrates NADP and
      nicotinic acid. NAADP-induced Ca(2+) release is insensitive to heparin and 8
      NH(2)-cADPR, specific inhibitors of the InsP(3)- and cADPR-controlled mechanisms,
      respectively. However, NAADP-induced Ca(2+) release could be blocked by
      pretreatment with a subthreshold dose of NAADP, as previously observed in sea
      urchin eggs. Furthermore, the NAADP-gated Ca(2+) release pathway is independent
      of cytosolic free Ca(2+) and therefore incapable of operating Ca(2+)-induced
      Ca(2+) release. In contrast to the sea urchin system, the NAADP-gated Ca(2+)
      release pathway in plants is not blocked by L-type channel antagonists. The
      existence of multiple Ca(2+) mobilization pathways and Ca(2+) release sites might
      contribute to the generation of stimulus-specific Ca(2+) signals in plant cells.

PMID- 10890900
TI  - Dissecting the role of the golgi complex and lipid rafts in biosynthetic
      transport of cholesterol to the cell surface.
AB  - In this study, we compared the transport of newly synthesized cholesterol with
      that of influenza virus hemagglutinin (HA) from the endoplasmic reticulum to the
      plasma membrane. The arrival of cholesterol on the cell surface was monitored by
      cyclodextrin removal, and HA transport was monitored by surface trypsinization
      and endoglycosidase H digestion. We found that disassembly of the Golgi complex
      by brefeldin A treatment resulted in partial inhibition of cholesterol transport
      while completely blocking HA transport. Further, microtubule depolymerization by
      nocodazole inhibited cholesterol and HA transport to a similar extent. When the
      partitioning of cholesterol into lipid rafts was analyzed, we found that newly
      synthesized cholesterol began to associate with low-density detergent-resistant
      membranes rapidly after synthesis, before it was detectable on the cell surface,
      and its raft association increased further upon chasing. When cholesterol
      transport was blocked by using 15 degrees C incubation, the association of newly
      synthesized cholesterol with low-density detergent-insoluble membranes was
      decreased and cholesterol accumulated in a fraction with intermediate density.
      Our results provide evidence for the partial contribution of the Golgi complex to
      the transport of newly synthesized cholesterol to the cell surface and suggest
      that detergent-resistant membranes are involved in the process.

PMID- 10890901
TI  - A role for Src kinase in spontaneous epileptiform activity in the CA3 region of
      the hippocampus.
AB  - Members of the Src family of nonreceptor protein tyrosine kinases (PTKs) have
      been implicated in the regulation of cellular excitability and synaptic
      plasticity. We have investigated the role of these PTKs in in vitro models of
      epileptiform activity. Spontaneous epileptiform discharges were induced in vitro
      in the CA3 region of rat hippocampal slices by superfusion with the potassium
      channel blocker 4-aminopyridine in Mg(2+)-free medium. In hippocampal slices
      treated in this fashion, Src kinase activity was increased and the frequency of
      epileptiform discharges could be greatly reduced by inhibitor of the Src family
      of PTKs, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2),
      but not by the inactive structural analog 4-amino-7-phenylpyrazol[3,4
      d]pyrimidine (PP3). 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4
      d]pyrimidine also reduced epileptiform activity induced by either 4-aminopyridine
      or Mg(2+)-free medium alone. These observations demonstrate a role for Src family
      PTKs in the pathophysiology of epilepsy and suggest potential therapeutic targets
      for antiepileptic therapy.

PMID- 10890902
TI  - A relationship between behavior, neurotrophin expression, and new neuron
      survival.
AB  - The high vocal center (HVC) controls song production in songbirds and sends a
      projection to the robust nucleus of the archistriatum (RA) of the descending
      vocal pathway. HVC receives new neurons in adulthood. Most of the new neurons
      project to RA and replace other neurons of the same kind. We show here that
      singing enhances mRNA and protein expression of brain-derived neurotrophic factor
      (BDNF) in the HVC of adult male canaries, Serinus canaria. The increased BDNF
      expression is proportional to the number of songs produced per unit time. Singing
      induced BDNF expression in HVC occurs mainly in the RA-projecting neurons.
      Neuronal survival was compared among birds that did or did not sing during days
      31-38 after BrdUrd injection. Survival of new HVC neurons is greater in the
      singing birds than in the nonsinging birds. A positive causal link between
      pathway use, neurotrophin expression, and new neuron survival may be common among
      systems that recruit new neurons in adulthood.

PMID- 10890903
TI  - Role of cysteines in Plasmodium falciparum circumsporozoite protein: interactions
      with heparin can rejuvenate inactive protein mutants.
AB  - Various pathogenic bacteria, viruses, and protozoan bind to glycosaminoglycan
      based receptors on host cells and initiate an infection. Sporozoites of
      Plasmodium predominantly express circumsporozoite (CS) protein on their surface,
      which binds to heparan sulfate proteoglycans on liver cell surface that
      subsequently leads to malaria. Here we show that the interaction of free heparin
      with this parasite ligand has the potential to be a critical component of
      invasion. CS protein of P. falciparum contains four cysteines at positions 361,
      365, 396, and 401. In this study, all four cysteine residues were mutagenized to
      alanine both individually and in different combinations. Conversion of cysteine
      396 to alanine (protein CS3) led to a 10-fold increase in the binding activity of
      the protein to HepG2 cells. Replacement of cysteines at positions 361, 365, and
      401 either alone or in different combinations led to a near total loss of
      binding. Surprisingly, activity in these inactive mutants could be effectively
      restored in the presence of submolar concentrations of heparin. Heparin also up
      regulated binding of CS3 at submolar concentrations with respect to the protein
      but down-regulated binding when present in excess. Given the significantly
      different concentrations of heparin in different organs of the host and the in
      vitro results described here one can consider in vivo ramifications of this
      phenomenon for pathogen targeting of specific organs and for the functional
      effects of antigenic variation on receptor ligand interaction.

PMID- 10890904
TI  - Sensitive detection of DNA polymorphisms by the serial invasive signal
      amplification reaction.
AB  - The invasive signal amplification reaction has been previously developed for
      quantitative detection of nucleic acids and discrimination of single-nucleotide
      polymorphisms. Here we describe a method that couples two invasive reactions into
      a serial isothermal homogeneous assay using fluorescence resonance energy
      transfer detection. The serial version of the assay generates more than 10(7)
      reporter molecules for each molecule of target DNA in a 4-h reaction; this
      sensitivity, coupled with the exquisite specificity of the reaction, is
      sufficient for direct detection of less than 1,000 target molecules with no prior
      target amplification. Here we present a kinetic analysis of the parameters
      affecting signal and background generation in the serial invasive signal
      amplification reaction and describe a simple kinetic model of the assay. We
      demonstrate the ability of the assay to detect as few as 600 copies of the
      methylene tetrahydrofolate reductase gene in samples of human genomic DNA. We
      also demonstrate the ability of the assay to discriminate single base differences
      in this gene by using 20 ng of human genomic DNA.

PMID- 10890905
TI  - Two-dimensional infrared spectroscopy of peptides by phase-controlled femtosecond
      vibrational photon echoes.
AB  - Two-dimensional infrared spectra of peptides are introduced that are the direct
      analogues of two- and three-pulse multiple quantum NMR. Phase matching and
      heterodyning are used to isolate the phase and amplitudes of the electric fields
      of vibrational photon echoes as a function of multiple pulse delays. Structural
      information is made available on the time scale of a few picoseconds. Line
      narrowed spectra of acyl-proline-NH(2) and cross peaks implying the coupling
      between its amide-I modes are obtained, as are the phases of the various
      contributions to the signals. Solvent-sensitive structural differences are seen
      for the dipeptide. The methods show great promise to measure structure changes in
      biology on a wide range of time scales.

PMID- 10890906
TI  - Brain-wave representation of words by superposition of a few sine waves.
AB  - Data from three previous experiments were analyzed to test the hypothesis that
      brain waves of spoken or written words can be represented by the superposition of
      a few sine waves. First, we averaged the data over trials and a set of subjects,
      and, in one case, over experimental conditions as well. Next we applied a Fourier
      transform to the averaged data and selected those frequencies with high energy,
      in no case more than nine in number. The superpositions of these selected sine
      waves were taken as prototypes. The averaged unfiltered data were the test
      samples. The prototypes were used to classify the test samples according to a
      least-squares criterion of fit. The results were seven of seven correct
      classifications for the first experiment using only three frequencies, six of
      eight for the second experiment using nine frequencies, and eight of eight for
      the third experiment using five frequencies.

PMID- 10890907
TI  - Sustained activation of Ras/Raf/mitogen-activated protein kinase cascade by the
      tumor suppressor p53.
AB  - The p53 tumor suppressor gene can inhibit proliferation transiently, induce
      permanent cell-cycle arrest/senescence, or cause apoptosis depending on the
      cellular context. The mitogen-activated protein kinase (MAPK) cascade is known to
      play a crucial role in cell proliferation and differentiation. Moreover, the
      duration and intensity of MAPK activation can profoundly influence the biological
      response observed. We demonstrated that a sustained activation of MAPK cascade
      could be induced by wild-type p53 expression but not by p21(Waf1/Cip1).
      Furthermore, exposure of normal cells to DNA-damaging agents induced MAPK
      activation in a p53-dependent manner. Tumor-derived p53 mutants defective in DNA
      binding failed to activate MAPK, implying that p53 transcriptional activity is
      essential for this function. Finally, activation of MAPK by p53 was inhibited by
      expression of dominant-negative Ras (N17Ras) and Raf1 mutants, indicating that
      MAPK activation by p53 is mediated at a level upstream of Ras. All of these
      findings establish a biochemical link between p53 signaling and the Ras/Raf/MAPK
      cascade.

PMID- 10890908
TI  - Transgenic potato (Solanum tuberosum) tubers synthesize the full spectrum of
      inulin molecules naturally occurring in globe artichoke (Cynara scolymus) roots.
AB  - The ability to synthesize high molecular weight inulin was transferred to potato
      plants via constitutive expression of the 1-SST (sucrose:sucrose 1
      fructosyltransferase) and the 1-FFT (fructan: fructan 1-fructosyltransferase)
      genes of globe artichoke (Cynara scolymus). The fructan pattern of tubers from
      transgenic potato plants represents the full spectrum of inulin molecules present
      in artichoke roots as shown by high-performance anion exchange chromatography, as
      well as size exclusion chromatography. These results demonstrate in planta that
      the enzymes sucrose:sucrose 1-fructosyltransferase and fructan:fructan 1
      fructosyltransferase are sufficient to synthesize inulin molecules of all chain
      lengths naturally occurring in a given plant species. Inulin made up 5% of the
      dry weight of transgenic tubers, and a low level of fructan production also was
      observed in fully expanded leaves. Although inulin accumulation did not influence
      the sucrose concentration in leaves or tubers, a reduction in starch content
      occurred in transgenic tubers, indicating that inulin synthesis did not increase
      the storage capacity of the tubers.

PMID- 10890910
TI  - Induction of wild-type p53 activity in human cancer cells by ribozymes that
      repair mutant p53 transcripts.
AB  - Several groups have attempted to develop gene therapy strategies to treat cancer
      via introduction of the wild-type (wt) p53 cDNA into cancer cells. Unfortunately,
      these approaches do not result in regulated expression of the p53 gene and do not
      reduce expression of the mutant p53 that is overexpressed in cancerous cells.
      These shortcomings may greatly limit the utility of this gene replacement
      approach. We describe an alternative strategy with trans-splicing ribozymes that
      can simultaneously reduce mutant p53 expression and restore wt p53 activity in
      various human cancers. The ribozyme accomplished such conversion by repairing
      defective p53 mRNAs with high fidelity and specificity. The corrected transcripts
      were translated to produce functional p53 that can transactivate p53-responsive
      promoters and down-modulate expression of the multidrug resistance (MDR1) gene
      promoter. The level of wt p53 activity generated was significant, resulting in a
      23-fold induction of a p53-responsive promoter and a 3-fold reduction in MDR1
      promoter expression in transfected cancer cells. Once efficient delivery systems
      are developed, this strategy should prove useful for making human cancers more
      responsive to p53 activity and more sensitive to chemotherapeutic agents.

PMID- 10890909
TI  - Acute systemic inflammation up-regulates secretory sphingomyelinase in vivo: a
      possible link between inflammatory cytokines and atherogenesis.
AB  - Inflammation plays a critical role in atherogenesis, yet the mediators linking
      inflammation to specific atherogenic processes remain to be elucidated. One such
      mediator may be secretory sphingomyelinase (S-SMase), a product of the acid
      sphingomyelinase gene. The secretion of S-SMase by cultured endothelial cells is
      induced by inflammatory cytokines, and in vivo data have implicated S-SMase in
      subendothelial lipoprotein aggregation, macrophage foam cell formation, and
      possibly other atherogenic processes. Thus, the goal of this study was to seek
      evidence for S-SMase regulation in vivo during a physiologically relevant
      inflammatory response. First, wild-type mice were injected with saline or
      lipopolysaccharide (LPS) as a model of acute systemic inflammation. Serum S-SMase
      activity 3 h postinjection was increased 2- to 2.5-fold by LPS (P < 0.01). To
      determine the role of IL-1 in the LPS response, we used IL-1 converting enzyme
      knockout mice, which exhibit deficient IL-1 bioactivity. The level of serum S
      SMase activity in LPS-injected IL-1 converting enzyme knockout mice was
      approximately 35% less than that in identically treated wild-type mice (P <
      0.01). In LPS-injected IL-1-receptor antagonist knockout mice, which have an
      enhanced response to IL-1, serum S-SMase activity was increased 1. 8-fold
      compared with LPS-injected wild-type mice (P < 0.01). Finally, when wild-type
      mice were injected directly with IL-1beta, tumor necrosis factor alpha, or both,
      serum S-SMase activity increased 1. 6-, 2.3-, and 2.9-fold, respectively (P <
      0.01). These data show regulation of S-SMase activity in vivo and they raise the
      possibility that local stimulation of S-SMase may contribute to the effects of
      inflammatory cytokines in atherosclerosis.

PMID- 10890911
TI  - Association of Smads with lymphoid enhancer binding factor 1/T cell-specific
      factor mediates cooperative signaling by the transforming growth factor-beta and
      wnt pathways.
AB  - The transforming growth factor-beta (TGFbeta) and Wnt/wingless pathways play
      pivotal roles in tissue specification during development. Activation of Smads,
      the effectors of TGFbeta superfamily signals, results in Smad translocation from
      the cytoplasm into the nucleus where they act as transcriptional comodulators to
      regulate target gene expression. Wnt/wingless signals are mediated by the DNA
      binding HMG box transcription factors lymphoid enhancer binding factor 1/T cell
      specific factor (LEF1/TCF) and their coactivator beta-catenin. Herein, we show
      that Smad3 physically interacts with the HMG box domain of LEF1 and that TGFbeta
      and Wnt pathways synergize to activate transcription of the Xenopus homeobox gene
      twin (Xtwn). Disruption of specific Smad and LEF1/TCF DNA-binding sites in the
      promoter abrogates synergistic activation of the promoter. Consistent with this
      observation, introduction of Smad sites into a TGFbeta-insensitive LEF1/TCF
      target gene confers cooperative TGFbeta and Wnt responsiveness to the promoter.
      Furthermore, we demonstrate that TGFbeta-dependent activation of LEF1/TCF target
      genes can occur in the absence of beta-catenin binding to LEF1/TCF and requires
      both Smad and LEF1/TCF DNA-binding sites in the Xtwn promoter. Thus, our results
      show that TGFbeta and Wnt signaling pathways can independently or cooperatively
      regulate LEF1/TCF target genes and suggest a model for how these pathways can
      synergistically activate target genes.

PMID- 10890912
TI  - Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a
      model for viral DNA binding.
AB  - Insolubility of full-length HIV-1 integrase (IN) limited previous structure
      analyses to individual domains. By introducing five point mutations, we
      engineered a more soluble IN that allowed us to generate multidomain HIV-1 IN
      crystals. The first multidomain HIV-1 IN structure is reported. It incorporates
      the catalytic core and C-terminal domains (residues 52-288). The structure
      resolved to 2.8 A is a Y-shaped dimer. Within the dimer, the catalytic core
      domains form the only dimer interface, and the C-terminal domains are located 55
      A apart. A 26-aa alpha-helix, alpha6, links the C-terminal domain to the
      catalytic core. A kink in one of the two alpha6 helices occurs near a known
      proteolytic site, suggesting that it may act as a flexible elbow to reorient the
      domains during the integration process. Two proteins that bind DNA in a sequence
      independent manner are structurally homologous to the HIV-1 IN C-terminal domain,
      suggesting a similar protein-DNA interaction in which the IN C-terminal domain
      may serve to bind, bend, and orient viral DNA during integration. A strip of
      positively charged amino acids contributed by both monomers emerges from each
      active site of the dimer, suggesting a minimally dimeric platform for binding
      each viral DNA end. The crystal structure of the isolated catalytic core domain
      (residues 52-210), independently determined at 1.6-A resolution, is identical to
      the core domain within the two-domain 52-288 structure.

PMID- 10890913
TI  - Genetic control of resistance to experimental infection with virulent
      Mycobacterium tuberculosis.
AB  - Over 2 billion people are estimated to be infected with virulent Mycobacterium
      tuberculosis, yet fewer than 10% progress to clinical tuberculosis within their
      lifetime. Twin studies and variations in the outcome of tuberculosis infection
      after exposure to similar environmental risks suggest genetic heterogeneity among
      individuals in their susceptibility to disease. In a mouse model of tuberculosis,
      we have established that resistance and susceptibility to virulent M.
      tuberculosis is a complex genetic trait. A new locus with a major effect on
      tuberculosis susceptibility, designated sst1 (susceptibility to tuberculosis 1),
      was mapped to a 9-centimorgan (cM) interval on mouse chromosome 1. It is located
      10-19 cM distal to a previously identified gene, Nramp1, that controls the innate
      resistance of mice to the attenuated bacillus Calmette-Guerin vaccine strain. The
      phenotypic expression of the newly identified locus is distinct from that of
      Nramp1 in that sst1 controls progression of tuberculosis infection in a lung
      specific manner. Mice segregating at the sst1 locus exhibit marked differences in
      the growth rates of virulent tubercle bacilli in the lungs. Lung lesions in
      congenic sst1-susceptible mice are characterized by extensive necrosis and
      unrestricted extracellular multiplication of virulent mycobacteria, whereas sst1
      resistant mice develop interstitial granulomas and effectively control
      multiplication of the bacilli. The resistant allele of sst1, although powerful in
      controlling infection, is not sufficient to confer full protection against
      virulent M. tuberculosis, indicating that other genes located outside of the sst1
      locus are likely also to be important for controlling tuberculosis infection.

PMID- 10890914
TI  - CD1c molecules broadly survey the endocytic system.
AB  - The ability of antigen-presenting cells to sample distinct intracellular
      compartments is crucial for microbe detection. Major histocompatibility complex
      class I and class II molecules sample the cytosol or the late endocytic
      compartment, allowing detection of microbial peptide antigens that arise in
      distinct intracellular compartments. In contrast, CD1a and CD1b molecules mediate
      the presentation of lipid and glycolipid antigens and differentially sample early
      recycling endosomes or late endocytic compartments, respectively, that contain
      distinct sets of lipid antigens. Here, we show that, unlike the other CD1
      isoforms or major histocompatibility complex molecules that each sample
      restricted only intracellular compartments, CD1c is remarkable in that it
      distributes broadly throughout the endocytic system and is expressed in both
      recycling endosomes and late endocytic compartments. Further, in contrast to
      CD1b, which requires an acidic environment to function, antigen presentation by
      CD1c was able to overcome dependence on vesicular acidification. Because CD1c is
      expressed on essential antigen-presenting cells, such as epidermal Langerhans
      cells (in the absence of CD1b), or on B cells (without CD1a or -b), we suggest
      that CD1c molecules allow a comprehensive survey for lipid antigens throughout
      the endocytic system even in the absence of other CD1 isoforms.

PMID- 10890915
TI  - Artificial ecosystem selection.
AB  - Artificial selection has been practiced for centuries to shape the properties of
      individual organisms, providing Darwin with a powerful argument for his theory of
      natural selection. We show that the properties of whole ecosystems can also be
      shaped by artificial selection procedures. Ecosystems initiated in the laboratory
      vary phenotypically and a proportion of the variation is heritable, despite the
      fact that the ecosystems initially are composed of thousands of species and
      millions of individuals. Artificial ecosystem selection can be used for practical
      purposes, illustrates an important role for complex interactions in evolution,
      and challenges a widespread belief that selection is most effective at lower
      levels of the biological hierarchy.

PMID- 10890916
TI  - Bacterial-type DNA holliday junction resolvases in eukaryotic viruses.
AB  - Homologous DNA recombination promotes genetic diversity and the maintenance of
      genome integrity, yet no enzymes with specificity for the Holliday junction (HJ)
      a key DNA recombination intermediate-have been purified and characterized from
      metazoa or their viruses. Here we identify critical structural elements of RuvC,
      a bacterial HJ resolvase, in uncharacterized open reading frames from poxviruses
      and an iridovirus. The putative vaccinia virus resolvase was expressed as a
      recombinant protein, affinity purified, and shown to specifically bind and cleave
      a synthetic HJ to yield nicked duplex molecules. Mutation of either of two
      conserved acidic amino acids abrogated the catalytic activity of the A22R protein
      without affecting HJ binding. The presence of bacterial-type enzymes in metazoan
      viruses raises evolutionary questions.

PMID- 10890917
TI  - A peptide derived from the non-receptor-binding region of urokinase plasminogen
      activator inhibits glioblastoma growth and angiogenesis in vivo in combination
      with cisplatin.
AB  - The urokinase plasminogen activator system is involved in angiogenesis and tumor
      growth of malignant gliomas, which are highly neovascularized and so may be
      amenable to antiangiogenic therapy. In this paper, we describe the activity of
      A6, an octamer capped peptide derived from the non-receptor-binding region of
      urokinase plasminogen activator. A6 inhibited human microvascular endothelial
      cell migration but had no effect on the proliferation of human microvascular
      endothelial cells or U87MG glioma cells in vitro. In contrast, A6 or cisplatin
      (CDDP) alone suppressed subcutaneous tumor growth in vivo by 48% and 53%,
      respectively, and, more strikingly, the combination of A6 plus CDDP inhibited
      tumor growth by 92%. Such combination treatment also greatly reduced the volume
      of intracranial tumor xenografts and increased survival of tumor-bearing animals
      when compared with CDDP or A6 alone. Tumors from the combination treatment group
      had significantly reduced neovascularization, suggesting a mechanism involving A6
      mediated inhibition of endothelial cell motility, thereby eliciting vascular
      sensitivity to CDDP-mediated toxicity. These data suggest that the combination of
      an angiogenesis inhibitor that targets endothelial cells with a cytotoxic agent
      may be a useful therapeutic approach.

PMID- 10890918
TI  - Inhibition of MHC class I-restricted antigen presentation by gamma 2
      herpesviruses.
AB  - The gamma-herpesviruses, in contrast to the alpha- and beta-herpesviruses, are
      not known to inhibit antigen presentation to CD8(+) cytotoxic T lymphocytes
      (CTLs) during lytic cycle replication. However, murine gamma-herpesvirus 68
      causes a chronic lytic infection in CD4(+) T cell-deficient mice despite the
      persistence of a substantial CTL response, suggesting that CTL evasion occurs.
      Here we show that, distinct from host protein synthesis shutoff, gamma
      herpesvirus 68 down-regulates surface MHC class I expression on lytically
      infected fibroblasts and inhibits their recognition by antigen-specific CTLs. The
      viral K3 gene, encoding a zinc-finger-containing protein, dramatically reduced
      the half-life of nascent class I molecules and the level of surface MHC class I
      expression and was by itself sufficient to block antigen presentation. The
      homologous K3 and K5 genes of the related Kaposi's sarcoma-associated virus also
      inhibited antigen presentation and decreased cell surface expression of HLA class
      I antigens. Thus it appears that an immune evasion strategy shared by at least
      two gamma-herpesviruses allows continued lytic infection in the face of strong
      CTL immunity.

PMID- 10890919
TI  - Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric
      complexes.
AB  - The possible molecular basis for the previously described antagonistic
      interactions between adenosine A(1) receptors (A(1)R) and dopamine D(1) receptors
      (D(1)R) in the brain have been studied in mouse fibroblast Ltk(-) cells
      cotransfected with human A(1)R and D(1)R cDNAs or with human A(1)R and dopamine
      D(2) receptor (long-form) (D(2)R) cDNAs and in cortical neurons in culture. A(1)R
      and D(1)R, but not A(1)R and D(2)R, were found to coimmunoprecipitate in
      cotransfected fibroblasts. This selective A(1)R/D(1)R heteromerization
      disappeared after pretreatment with the D(1)R agonist, but not after combined
      pretreatment with D(1)R and A(1)R agonists. A high degree of A(1)R and D(1)R
      colocalization, demonstrated in double immunofluorescence experiments with
      confocal laser microscopy, was found in both cotransfected fibroblast cells and
      cortical neurons in culture. On the other hand, a low degree of A(1)R and D(2)R
      colocalization was observed in cotransfected fibroblasts. Pretreatment with the
      A(1)R agonist caused coclustering (coaggregation) of A(1)R and D(1)R, which was
      blocked by combined pretreatment with the D(1)R and A(1)R agonists in both
      fibroblast cells and in cortical neurons in culture. Combined pretreatment with
      D(1)R and A(1)R agonists, but not with either one alone, substantially reduced
      the D(1)R agonist-induced accumulation of cAMP. The A(1)R/D(1)R heteromerization
      may be one molecular basis for the demonstrated antagonistic modulation of A(1)R
      of D(1)R receptor signaling in the brain. The persistence of A(1)R/D(1)R
      heteromerization seems to be essential for the blockade of A(1)R agonist-induced
      A(1)R/D(1)R coclustering and for the desensitization of the D(1)R agonist-induced
      cAMP accumulation seen on combined pretreatment with D(1)R and A(1)R agonists,
      which indicates a potential role of A(1)R/D(1)R heteromers also in
      desensitization mechanisms and receptor trafficking.

PMID- 10890920
TI  - Fundamental patterns underlying gene expression profiles: simplicity from
      complexity.
AB  - Analysis of previously published sets of DNA microarray gene expression data by
      singular value decomposition has uncovered underlying patterns or "characteristic
      modes" in their temporal profiles. These patterns contribute unequally to the
      structure of the expression profiles. Moreover, the essential features of a given
      set of expression profiles are captured using just a small number of
      characteristic modes. This leads to the striking conclusion that the
      transcriptional response of a genome is orchestrated in a few fundamental
      patterns of gene expression change. These patterns are both simple and robust,
      dominating the alterations in expression of genes throughout the genome.
      Moreover, the characteristic modes of gene expression change in response to
      environmental perturbations are similar in such distant organisms as yeast and
      human cells. This analysis reveals simple regularities in the seemingly complex
      transcriptional transitions of diverse cells to new states, and these provide
      insights into the operation of the underlying genetic networks.

PMID- 10890921
TI  - In vivo formation of complex microvessels lined by human endothelial cells in an
      immunodeficient mouse.
AB  - We have identified conditions for forming cultured human umbilical vein
      endothelial cells (HUVEC) into tubes within a three-dimensional gel that on
      implantation into immunoincompetent mice undergo remodeling into complex
      microvessels lined by human endothelium. HUVEC suspended in mixed
      collagen/fibronectin gels organize into cords with early lumena by 24 h and then
      apoptose. Twenty-hour constructs, s.c. implanted in immunodeficient mice, display
      HUVEC-lined thin-walled microvessels within the gel 31 days after implantation.
      Retroviral-mediated overexpression of a caspase-resistant Bcl-2 protein delays
      HUVEC apoptosis in vitro for over 7 days. Bcl-2-transduced HUVEC produce an
      increased density of HUVEC-lined perfused microvessels in vivo compared with
      untransduced or control-transduced HUVEC. Remarkably, Bcl-2- but not control
      transduced HUVEC recruit an ingrowth of perivascular smooth-muscle alpha-actin
      expressing mouse cells at 31 days, which organize by 60 days into HUVEC-lined
      multilayered structures resembling true microvessels. This system provides an in
      vivo model for dissecting mechanisms of microvascular remodeling by using
      genetically modified endothelium. Incorporation of such human endothelial-lined
      microvessels into engineered synthetic skin may improve graft viability,
      especially in recipients with impaired angiogenesis.

PMID- 10890922
TI  - Changes in brain cell shape create residual extracellular space volume and
      explain tortuosity behavior during osmotic challenge.
AB  - Diffusion of molecules in brain extracellular space is constrained by two
      macroscopic parameters, tortuosity factor lambda and volume fraction alpha.
      Recent studies in brain slices show that when osmolarity is reduced, lambda
      increases while alpha decreases. In contrast, with increased osmolarity, alpha
      increases, but lambda attains a plateau. Using homogenization theory and a
      variety of lattice models, we found that the plateau behavior of lambda can be
      explained if the shape of brain cells changes nonuniformly during the shrinking
      or swelling induced by osmotic challenge. The nonuniform cellular shrinkage
      creates residual extracellular space that temporarily traps diffusing molecules,
      thus impeding the macroscopic diffusion. The paper also discusses the definition
      of tortuosity and its independence of the measurement frame of reference.

PMID- 10890923
TI  - Structure-activity analysis of buforin II, a histone H2A-derived antimicrobial
      peptide: the proline hinge is responsible for the cell-penetrating ability of
      buforin II.
AB  - Buforin II is a 21-aa potent antimicrobial peptide that forms, in a hydrophobic
      medium, an amphipathic structure consisting of an N-terminal random coil region
      (residues 1-4), an extended helical region (residues 5-10), a hinge (residue 11),
      and a C-terminal regular alpha-helical region (residues 12-21). To elucidate the
      structural features of buforin II that are required for its potent antimicrobial
      activity, we synthesized a series of N- and C-terminally truncated or amino acid
      substituted synthetic buforin II analogs and examined their antimicrobial
      activity and mechanism of action. Deletion of the N-terminal random coil region
      increased the antibacterial activity approximately 2-fold, but further N-terminal
      truncation yielded peptide analogs with progressively decreasing activity.
      Removal of four amino acids from the C-terminal end of buforin II resulted in a
      complete loss of antimicrobial activity. The substitution of leucine for the
      proline hinge decreased significantly the antimicrobial activity. Confocal
      fluorescence microscopic studies showed that buforin II analogs with a proline
      hinge penetrated the cell membrane without permeabilization and accumulated in
      the cytoplasm. However, removal of the proline hinge abrogated the ability of the
      peptide to enter cells, and buforin II analogs without a proline hinge localized
      on the cell surface, permeabilizing the cell membrane. In addition, the cell
      penetrating efficiency of buforin II and its truncated analogs, which depended on
      the alpha-helical content of the peptides, correlated linearly with their
      antimicrobial potency. Our results demonstrate clearly that the proline hinge is
      responsible for the cell-penetrating ability of buforin II, and the cell
      penetrating efficiency determines the antimicrobial potency of the peptide.

PMID- 10890924
TI  - The role of antigen and IL-12 in sustaining Th1 memory cells in vivo: IL-12 is
      required to maintain memory/effector Th1 cells sufficient to mediate protection
      to an infectious parasite challenge.
AB  - IL-12 plays a central role in both the induction and magnitude of a primary Th1
      response. A critical question in designing vaccines for diseases requiring Th1
      immunity such as Mycobacterium tuberculosis and Leishmania major is the
      requirements to sustain memory/effector Th1 cells in vivo. This report examines
      the role of IL-12 and antigen in sustaining Th1 responses sufficient for
      protective immunity to L. major after vaccination with LACK protein (LP) plus rIL
      12 and LACK DNA. It shows that, after initial vaccination with LP plus rIL-12,
      supplemental boosting with either LP or rIL-12 is necessary but not sufficient to
      fully sustain long-term Th1 immunity. Moreover, endogenous IL-12 is also shown to
      be required for the induction, maintenance, and effector phase of the Th1
      response after LACK DNA vaccination. Finally, IL-12 is required to sustain Th1
      cells and control parasite growth in susceptible and resistant strains of mice
      during primary and secondary infection. Taken together, these data show that IL
      12 is essential to sustain a sufficient number of memory/effector Th1 cells
      generated in vivo to mediate long-term protection to an intracellular pathogen.

PMID- 10890925
TI  - Accidental childhood death and the role of the pathologist.
AB  - The following study provides an overview of accidental childhood death. This
      study is based on a review of 369 cases of fatal childhood accidents taken from
      the records of the Department of Histopathology, Women's and Children's Hospital,
      Adelaide, Australia, over a 34-year period from 1963 to 1996. Data provide
      information on deaths due to motor vehicle accidents, drownings, accidental
      asphyxia, burns, poisonings, electrocution, and miscellaneous trauma. In
      addition, certain categories have undergone further examination, including
      asphyxial deaths due to unsafe sleeping environments and unsafe eating practices,
      drowning deaths, and deaths on farms, following identification of significant
      child safety problems in these areas as part of the "Keeping Your Baby and Child
      Safe" program. Previously unrecognized dangers to children detected through this
      program include mesh-sided cots, V-shaped pillows, and certain types of stroller
      prams. The production of information pamphlets and packages for parents and the
      recall of certain dangerous products following recommendations made by
      pathologists demonstrate that pediatric and forensic pathologists have an
      important role to play in preventive medicine issues and in formulating public
      health strategies.

PMID- 10890926
TI  - Very low birthweight Infant's placenta and its relation to pregnancy and fetal
      characteristics.
AB  - Our objective was to relate pathology of the very low birthweight (VLBW) infant's
      placenta to pregnancy and fetal characteristics. We correlated the pathologic
      features of 1146 placentas from infants with birth weights of 500-1500 g who were
      born between 1/1/91 and 12/31/93 to the number of gestations per pregnancy,
      initiator of preterm delivery, gestational age, birth weight Z score, and
      duration of rupture of membrane (ROM). Placental correlates of acute inflammation
      and villous edema were associated with preterm labor (PTL), prelabor premature
      rupture of membranes (PROM), lower gestational age, and higher birth weight Z
      score. In PTL pregnancies delivered within 1 h of membrane rupture, 61% of
      placentas already had membrane inflammation. Placental correlates of pregnancy
      induced hypertension (PIH) were seen more commonly with PIH pregnancies, older
      gestational age, and lower birth weight Z score. We found a more prominent
      histopathologic signature for singleton than for multiple gestation placentas.
      The placental pathologic findings associated with the clinical diagnoses of
      infection, PIH, and low-birth weight Z scores in our VLBW/preterm population are
      similar to those in the literature regarding term pregnancies. The presence of
      multiple histologic findings consistent with inflammation in placentas of PTL
      pregnancies with duration of ROM lasting <1 h suggests that some cases of PTL are
      precipitated by a more long-standing infection than that previously suspected.
      Morphologic placental features appear to be correlates of the phenomena leading
      to premature delivery. Examination of the VLBW infant's placenta provides insight
      into the etiology and management of VLBW/preterm deliveries.

PMID- 10890927
TI  - Very low birthweight placenta: clustering of morphologic characteristics.
AB  - Our objective was to use factor analysis as a data reduction tool to organize a
      large number of placental pathologic features into useful aggregates. We examined
      1146 placentas of live-born infants with a birth weight of 500-1500 g. We then
      conducted analyses of pairs of characteristics and multiple characteristics to
      identify "associated groups" and "factors," respectively. We found an associated
      group and factor that had placental features associated with acute inflammation
      and another associated group and factor that had features associated with
      vasculopathy. Acute umbilical vasculitis had the strongest correlation with other
      features of the acute inflammation associated group and factor. Gross evidence of
      acute inflammation (opacification and green appearance of membrane) was
      eliminated in the reduction from associated group to factor. Infarcts and
      syncytial knots were strongly dissociated with features of acute inflammation.
      The multiple pathologic features of the very low birthweight placenta can be
      aggregated into two associated groups or two factors. Lack of membrane
      opacification cannot be used as a criterion for declining microscopic
      examination. The absence of infarcts and syncytial knots should prompt a search
      for features of acute inflammation. If a placenta has two or more findings from
      the acute inflammation factor or the vasculopathy factor, it is unlikely to
      demonstrate features from the other factor.

PMID- 10890928
TI  - Embryonic and early fetal development of human lung vasculature and its
      functional implications.
AB  - Recently, we have identified in the mouse three processes involved in the early
      development of pulmonary vasculature: angiogenesis for branching of central
      vessels, vasculogenesis (lakes in the mesenchyme) for peripheral vessels, and a
      lytic process to establish luminal connection between the two. We have
      established that these three processes also operate in the human by studying
      serial sections of human embryos and early fetuses. Vascular lakes of
      hematopoietic cells appear at stage 13, i.e., 4+ weeks gestational age (GA), the
      first intrapulmonary vascular structure to appear. At stage 20 (50.5 days GA), a
      venous network with luminal connections to central pulmonary veins (PV) is
      present. Airways have not yet reached these regions of lung. At its first
      intrapulmonary appearance, the pulmonary artery (PA) is small and thick walled:
      it runs with the airway but its branching is slower, so many peripheral airways
      are not accompanied by a PA branch. By contrast, the PV has a peripheral patent
      network well before the PA. In the pseudoglandular phase, airway branching
      continues, and the PA catches up so that small PA branches are found with all
      airways. Later in this phase small nonmuscular vessels lie in the mesenchyme
      close to airway epithelium. By the early canalicular phase and the age of
      viability, continuity between pulmonary artery and the peripheral capillary
      network must be established. In a 10-week fetus several structures suggesting a
      breakthrough site were seen. Air-blood barrier structure is first seen at 19
      weeks. Thus in the lung, the PA and PV are dissociated in their timing and
      pattern of branching. Early veins are present diffusely through the mesenchyme
      and establish central luminal connection to the main pulmonary vein before airway
      or artery are present at this level.

PMID- 10890929
TI  - Renal developmental delay expressed by reduced glomerular number and its
      association with growth retardation in victims of sudden infant death syndrome
      and in "normal" infants.
AB  - In victims of sudden infant death syndrome (SIDS), renal development has been
      reported to be significantly impaired. In the present study, we used
      stereological techniques to estimate volume of kidney cortex and total number of
      glomeruli in a group of human infants. Infants were classified according to cause
      of death-SIDS or non-SIDS. Cases were further subdivided according to birth
      weight-normal birth weight (NBW) or low birth weight (LBW) (we were unable to
      identify any non-SIDS LBW infants for our study). No significant differences were
      found between NBW and LBW infants (irrespective of cause of death) for cortical
      volume, glomerular density, or total glomerular number (p > 0.140). Kidney
      cortical volume, glomerular density, and total glomerular number were not
      significantly different between SIDS and non-SIDS infants (p > 0.510). Glomerular
      number was only significantly less in SIDS infants of LBW (p = 0. 032) than in
      controls according to the Wilcoxon rank sum test; using the Kruskal-Wallis for
      one-way analysis, no significant difference was found (p > 0.010). These results
      contrast with those from previous studies, as a reduction in glomerular number
      was not noted in SIDS NBW infants, and the mean value for the control (non-SIDS
      NBW) group was significantly reduced (p < 0.01) from those of previous studies.
      This indicates that glomerular number reduction is seen in SIDS NBW and non-SIDS
      NBW cases and is therefore directly associated with growth retardation rather
      than with SIDS.

PMID- 10890930
TI  - Expression of thyroid transcription factor-1 in congenital cystic adenomatoid
      malformation of the lung.
AB  - Congenital cystic adenomatoid malformation (CCAM) is an abnormality of branching
      morphogenesis of the lung. CCAM types 1, 2, and 3 exhibit a cellular composition
      that is different from that of CCAM type 4 when evaluated with bronchiolar and
      alveolar cell markers. Thyroid transcription factor 1 (TTF-1) regulates early
      lung development. To evaluate the potential role of TTF-1 in the development of
      CCAM, TTF-1 expression in CCAM was compared to that of fetal lungs at varying
      gestational ages. Twenty-three CCAM cases (17 type 1, two type 2, two type 3, and
      two type 4) and 11 fetal lungs (3 pseudoglandular, 4 canalicular, and 4 terminal
      sac stages) were analyzed using a rabbit polyclonal antiserum to rat TTF-1.
      Nuclear staining for TTF-1 was observed in ciliated and nonciliated cells of the
      bronchial and bronchiolar epithelia and in cells lining the distal air spaces by
      12 weeks gestational age. By mid-gestation, proximal bronchial cells were TTF-1
      negative, except for the basal cells, while TTF-1 staining was maintained in
      distal bronchiolar and alveolar cells. TTF-1 expression decreased in both
      bronchial, bronchiolar, and alveolar epithelia with advancing gestational age and
      cytodifferentiation. At term, TTF-1 expression persisted in a few bronchial and
      bronchiolar basal cells and in all alveolar type II cells, whereas type I cells
      were negative. In CCAM, TTF-1 was detected in the nuclei of epithelial cells
      lining the cysts. TTF-1 was expressed in a majority of the bronchiolar-like
      epithelial cells of the cysts in CCAM types 1, 2, and 3, where almost 100% of the
      cells were TTF-1 positive. In contrast, TTF-1 expression in the alveolar-like
      epithelium of CCAM type 4 cysts was restricted to type II cells and only 30%-60%
      of the lining cells were TTF-1 positive. These results support the hypothesis
      that CCAM types 1, 2, and 3 reflect abnormalities in lung morphogenesis and
      differentiation that are distinct from those for CCAM type 4. The role played by
      TTF-1 in the development of CCAM, if any, is not clear.

PMID- 10890931
TI  - Abnormal umbilical cord coiling is associated with adverse perinatal outcomes.
AB  - The normal umbilical cord coil index is one coil/5 cm, i.e., 0.2 +/- 0.1 coils
      completed per cm. We report the frequency and clinical correlations of abnormally
      coiled cords among 1329 cases referred to our placental pathology services.
      Twenty-one percent of cords were overcoiled and 13% were undercoiled. Abnormal
      cord coiling was seen at all gestational ages. Principal clinical correlations
      found in overcoiled cords were fetal demise (37%), fetal intolerance to labor
      (14%), intrauterine growth retardation (10%), and chorioamnionitis (10%). For
      undercoiled cords, the frequencies of these adverse outcomes were 29%, 21%, 15%,
      and 29%, respectively. Abnormal cord coiling was associated with thrombosis of
      chorionic plate vessels, umbilical venous thrombosis, and cord stenosis. Thus,
      abnormal cord coiling is a chronic state, established in early gestation, that
      may have chronic (growth retardation) and acute (fetal intolerance to labor and
      fetal demise) effects on fetal well-being. The cause of abnormal cord coiling is
      not known. Its effects on neurological status of survivors are also unknown.
      Antenatal detection of abnormal cord coil index by ultrasound could lead to
      elective delivery of fetuses at risk, thereby reducing the fetal death rate by
      about one-half. We recommend that the cord coil index become part of the routine
      placental pathology examination.

PMID- 10890932
TI  - Metanephric adenoma with embryonal hyperplasia of Bowman's capsular epithelium:
      previously unreported association.
AB  - We report a case of a 9-year-old boy with focal, segmental glomerulosclerosis
      who, following peritoneal dialysis, underwent renal transplantation and bilateral
      nephrectomy. The kidneys showed histological features of embryonal hyperplasia of
      Bowman's capsular epithelium, an uncommon lesion that is seen most often in
      patients with chronic renal failure who are being maintained on dialysis. In
      addition, a 1-cm tumor in the left kidney showed features of metanephric adenoma.
      Although both lesions are uncommon, they share many similarities on a
      morphological, immunohistochemical, and ultrastructural basis. This association
      has not been previously reported and may shed some light on the histogenesis of
      these recently described lesions.

PMID- 10890933
TI  - Use of multicolor spectral karyotyping in genetic analysis of pleuropulmonary
      blastoma.
AB  - Pleuropulmonary blastoma (PPB) is a rare, malignant intrathoracic pediatric
      tumor. It arises from the lung, pleura, or mediastinum and its pathogenesis and
      relationship to other pediatric solid tumors is not well understood. In this
      study, a case of PPB in a 3-year-old girl was studied using a combination of
      molecular genetic methods and cytogenetics. Molecular analysis of the commonly
      encountered fusion translocation gene products of pediatric solid tumors failed
      to detect a rearrangement. Cytogenetic analysis, supplemented by multicolor
      spectral karyotyping (SKY), identified an unbalanced translocation between
      chromosomes 1 and X, resulting in additional copies of 1q, an extra copy of Xq,
      and loss of part of Xp. In addition, trisomy 8 was detected. The identification
      of new chromosomal alterations and confirmation of previously reported ones in
      this rare neoplasm helps to improve our understanding of its pathogenesis and
      association with other pediatric tumors.

PMID- 10890934
TI  - Ovarian sarcoma with pathologic features of clear cell sarcoma of the kidney.
AB  - We report a case of an unusual sarcoma arising in the ovary of an infant girl.
      Histologically, the tumor was composed of clear, undifferentiated cells set in an
      arborizing vascular stroma. Immunohistochemical staining was positive only for
      vimentin. Ultrastructural evaluation demonstrated undifferentiated cells with
      interdigitating broad cell processes that encompassed irregular electron lucent
      spaces that contained flocculent extracellular material. Light and electron
      microscopic features of the tumor resembled a clear cell sarcoma of the kidney.
      Although the cell of origin is unproven, both tumors may arise from primitive
      mesenchymal cells that may not be restricted to the kidney.

PMID- 10890935
TI  - Synchronous wilms tumor and fibrolamellar hepatocellular carcinoma: report of a
      case.
AB  - Fibrolamellar hepatocellular carcinoma (FHCC) is a unique histologic variant of
      HCC that occurs in a younger subset of patients than classical HCC, and is
      associated with a better prognosis. Wilms tumor (WT) is a malignant embryonal
      neoplasm of the kidney and is one of the most common solid tumors of childhood,
      occurring at an estimated frequency of 1 in 8000 to 10,000 births. Although
      second malignant neoplasms (SMNs) following therapy for WTs have been reported in
      the liver, the coexistence of HCC and WT is extremely rare. We present the first
      report of a synchronous anaplastic WT and FHCC in a previously healthy 4-year-old
      girl. Despite the presence of focal immunohistochemical positivity for p53 in the
      WT, molecular analysis failed to reveal a germline or somatic p53 mutation, and
      was inconclusive in establishing a clonal relation between the two tumors.

PMID- 10890936
TI  - Adenomyoma arising in a meckel diverticulum: case report and review of the
      literature.
AB  - We report a case of adenomyoma of the small intestine arising in a Meckel
      diverticulum. The patient was a 22-month-old boy who presented with signs and
      symptoms of intussusception. At surgery, a Meckel diverticulum was found and
      removed. On histologic examination, a tumor consisting of dilated cystic glands
      and smooth muscle bundles was identified. A diagnosis of adenomyoma arising in a
      Meckel diverticulum was made. A review of the literature showed that only six
      other pediatric cases of adenomyoma of the small intestine have been reported.
      The presence of an adenomyoma in a young patient within a Meckel diverticulum
      favors the view that adenomyomas are a variant of pancreatic heterotopia.

PMID- 10890937
TI  - Early bacille de Calmette-Guerin vaccination and Crohn's disease: possible
      relationship?

PMID- 10890939
TI  - Letter to the editor (Reply)

PMID- 10890938
TI  - Sialoblastoma: association with cutaneous hamartoma (organoid nevus)?

PMID- 10890940
TI  - Neuroblastoma classification.

PMID- 10890942
TI  - Standardizing the evaluation of treatment outcomes after skin rejuvenation: the
      qualitative scoring system.
AB  - Current treatments to correct and reverse diseased or aged skin yield widely
      divergent results. Judging the outcome of such treatments is done in an arbitrary
      and subjective fashion that is often limited to a patient's feedback or the
      physician's opinion. This makes it difficult for inter-physician or physician
      patient agreement as to the degree of improvement achieved. In an age where skin
      rejuvenation is being widely practiced, a tremendous void needs to be filled by a
      system that appropriately evaluates and scores treatment outcomes. Such a system
      will help physicians communicate better in lectures, help them to better assess
      the results of various treatment modalities, and facilitate patient-doctor
      communication. The objective of this paper is to present a standardized scoring
      system against which skin rejuvenation results can be judged. This system is
      based on a model of healthy skin that can be defined by practical criteria
      against which patients can be judged pre- and post-skin rejuvenation procedures.
      A gold standard for healthy skin (baby skin) is established from a clinical,
      functional, and histologic perspective. Each patient's skin is compared with the
      healthy skin model and graded before and after treatment by implementing our
      scoring system which encompasses objective and subjective criteria. Objective
      criteria include the following skin characteristics: smoothness, firmness, even
      coloration, normal texture, and absence of any clinically evident disease.
      Subjective criteria include proper hydration and normal tolerance, and are not
      considered in the final scoring. Grading of each element in the scoring system
      [minimal (1), average (2), maximal (3)], and subsequently the final score
      [excellent (12 to 15), average (7 to 11), poor (<7)] are done with reference to
      the healthy skin model defined. The scoring system is novel and easy to use, and
      can be implemented to help improve communication between physicians and patients
      as well as during the dissemination of knowledge during medical conferences. In
      conclusion, treatment end-results can be consistently and more accurately
      assessed when the scoring system (based on objective criteria and a model of
      healthy skin) is used. Adopting this protocol will also help in directing our
      treatment to achieve the best possible results.

PMID- 10890943
TI  - Morphological aspects of dorsum and sacrum skin as related to liposuction.
AB  - Analysis of the dorsum's skin and sacrum region allowed the authors to evaluate
      regional characteristics of cutaneous skin integument, taking into consideration
      the age group most subjected to liposuction. Thus, it was attempted to establish
      rules to facilitate, in a comparative form, the evaluation of results related to
      cutaneous retraction in plastic surgery.

PMID- 10890944
TI  - Revision of neoclassical facial canons in young adult Afro-Americans.
AB  - The validity of seven neoclassical facial canons was tested in 100 young, adult,
      Afro-American (A-A) males and females, and the results were compared with 103
      North American Caucasians, producing the first reliable information about the
      differences of facial proportions in the two populations. Although the canons
      should not be regarded as strict directives in reconstructive and esthetic
      surgery, the data obtained from the study offered the first information about the
      facial proportion qualities of Afro-Americans in relation to the white
      population. In the absence of a detailed facial proportion study in A-As, the
      findings in canons can assist in planning the surgery. Comparison of the two
      populations revealed that the three sections of the facial profile were not equal
      in either population. In an A-A sample it showed the prevalence of the long lower
      face height also in relation to the height of the forehead. In horizontal canons
      of the orbital regions, the similarity between the two populations was
      demonstrated by the great frequency of intercanthal spaces to be wider than the
      length of the palpebral fissures [1]. The facial canons, including the nose
      width, relatively wider [2] in A-A than in white subjects, prompted the
      difference between A-A and Caucasians in frequency and degree in the dominant
      canon variations. The greater inclination of the nasal bridge than that of the
      medial longitudinal axis of the ear was a very frequent canon variation in both
      populations. Generally, the frequency of valid canons was greatly surpassed by
      their variations.

PMID- 10890945
TI  - Can a picture really paint a thousand words?
AB  - Plastic surgeons require a three-dimensional appreciation of form and function in
      order to meet reconstructive challenges. The popular perception that plastic
      surgeons must be artistic was tested in an observational study of sketch
      illustrations in plastic surgery case notes. Only in the trunk and breast
      category of illustrations could career plastic surgeons demonstrate superior
      artistic skill to non-career plastic surgeons and there was little correlation
      between the artistic merit of a diagram and the likelihood of its meaning being
      understood by an independent observer. Simple but accurate outline sketches are
      as capable of leading an observer to the correct diagnosis as complex works of
      art, while illustrations with low diagnostic scores are not only misleading but
      may also have medico-legal implications.

PMID- 10890946
TI  - Outcomes research in facial plastic surgery: a review and new directions.
AB  - Outcomes research is a fast-growing field of study that focuses on patient
      related aspects of medical or surgical outcomes such as satisfaction and quality
      of life. In the realm of facial plastic surgery, many outcomes are subjective
      evaluations based on the patient and physician's judgment as to the surgical
      result, but little has been done to quantify these qualitative results in an
      objective manner. This paper discusses the basis for outcomes research and
      suggests its application to the field of facial plastic surgery. Four new facial
      plastic outcomes instruments have been developed and are provided for the
      potential use in measuring the quality of life results of rhytidectomy,
      rhinoplasty, blepharoplasty, and skin rejuvenation procedures.

PMID- 10890947
TI  - Noninvasive treatment of bromidrosis by frequency-doubled Q-switched Nd:YAG
      laser.
AB  - Axillary bromidrosis (osmidrosis) is a common and disgusting disorder in Asian
      communities. Current treatments are basically invasive resulting in varying
      degrees of success and complications. The objective of this study was to
      investigate the efficacy of frequency-doubled Q-switched Nd:YAG laser as a
      possible noninvasive technique for treating axillary bromidrosis. Sixty-four
      axillae of 32 patients were lased by a single session of green light energy at
      the fluence of 3.5 joules at a 4-mm spot size. The follow-up time was 6-18 months
      (mean 15). Twenty-six patients (81.2%) showed good to excellent results, 4
      patients (12.5%) had fair results, and 2 (6. 2%) patients had poor results. The
      only side effect was a temporary hyperpigmentation at the periphery of the
      treated area in a few patients with dark skin color. In conclusion, frequency
      doubled Q-switched Nd:YAG laser is an effective noninvasive treatment for
      axillary bromidrosis.

PMID- 10890948
TI  - Staged TRAM breast reconstruction: combining the advantages of tissue expansion
      with surgical delay.
AB  - The TRAM flap has become the gold standard in breast reconstruction but suffers
      from the disadvantages of poor color match, different texture, and impaired
      sensation compared to the normal breast. This study reports on a two-stage
      procedure to address these problems. The first stage consists of insertion of a
      tissue expander and surgical delay of the TRAM flap. The second stage consists of
      removal of the tissue expander and transposition of a deepithelized TRAM flap
      into the tissue expanded cavity. (The capsule is excised.) Four cases of breast
      reconstruction are reported. The advantage of this procedure is that it offers
      the benefits of tissue expansion, viz., normal color match, texture, and
      sensation, and in addition, reconstruction is achieved with autologous tissue by
      a pedicled TRAM flap. The vascularity of the TRAM is enhanced by a surgical delay
      procedure.

PMID- 10890949
TI  - A new personal surgical procedure for breast reduction and lifting.
AB  - A series of patients operated from 1995 through 1997 is reviewed. The women
      ranged in age from 18 to 40 and were seen in either a university- or a private
      hospital setting. Thirty-eight of the patients underwent reduction mammaplasty,
      which was performed using an inferior pedicle technique with a straight-line
      incision; two patients underwent mastopexy only. The reduction procedure depends
      on the formation of a cap from medial, lateral, and superior flaps. Following
      resection of breast tissue the cap is joined to a cone-the nipple-areola complex
      carried on a subcutaneous inferior pedicle. The cone is fixed to the chest wall
      with simple vertical stitches, minimizing the recurrence of ptosis. This
      technique is safe and versatile, avoids a submammary scar, and offers an
      aesthetic and long-lasting result.

PMID- 10890950
TI  - Endoscopic transaxillary subglandular breast augmentation using silicone gel
      textured implants.
AB  - We present our experience with endoscopic transaxillary subglandular breast
      augmentation using textured silicon gel implants. Fourteen implants were placed
      in seven patients through a 4 cm axillary incision, in a subglandular pocket,
      with the help of a 10 mm, 30 degrees endoscope with a subcutaneous retractor and
      endoscopic diathermy. The implant was inserted with the help of a plastic bag. No
      drains were left in place. The duration of the procedure was 1 h 30 min in the
      most recent cases. Bleeding during surgery was kept to a minimum, and there were
      no complications such as capsular contracture, hematoma, or hypertrophic scar.
      Infection occurred in one implant and it was necessary to extract it. This
      technique is an excellent tool for patients requiring subglandular implants who
      prefer a distant incision. It provides good control over dissection and allows
      the use of silicone gel implants, thus avoiding the risk of deflation. In
      addition, recovery is faster and there is less bruising and pain.

PMID- 10890951
TI  - Subfascial endoscopic transaxillary augmentation mammaplasty.
AB  - Video endoscopy for breast hypoplasia and glabellar frown lines has been used
      since 1996 at our private clinic. Breast augmentation with an S-shape incision
      for transaxillary access is utilized to introduce the implant, in a submuscular
      or subglandular and, recently (since October 1998), in a subfascial location.
      From August 1998 through January 1999, 62 patients underwent endoscopic
      surgeries; 49 were submuscular, 5 subglandular, and 8 subfascial. McGhan 410,
      anatomical biodimensional implants 155 to 235 g, were used. We observed three
      cases of complications, two of them malpositioning (rotation), needing
      reoperation, and one hematoma, treated with drainage. Patient satisfaction was
      high, especially regarding the axillary incision. There have been no capsular
      contractions to date.

PMID- 10890952
TI  - Breast augmentation: teaching our patients how compression can help prevent
      capsular contracture.
AB  - If we insert a foreign body into a human being, physiologically, we get a
      capsular contracture because a periprosthetic scar contracts to give the implant
      a spherical shape, the smallest surface area for a given volume. To antagonize
      this contracture, one must stretch the periprosthetic scar and this can be
      accomplished with compression.

PMID- 10890953
TI  - New innovations in scar management.
AB  - As current aesthetic surgical techniques become more standardized and results
      more predictable, a fine scar may be the demarcating line between acceptable and
      unacceptable aesthetic results. With this in mind, a scar management program has
      been adopted based on the modalities of wound support, hydration, and hastened
      maturity, all factors gleaned from scientific evidence published over the past 25
      years. Tension on a scar in one axis will result in a stretched scar, probably
      initiated by neutrophils and their neutral proteases [18,26]. Tension on a scar
      from many directions or intermittently will result in a hypertrophic scar,
      possibly initiated by lymphocytes but definitely related to a prolongation of the
      inflammatory process, with increased fibroblast activity and overabundant
      extracellular matrix secretion [24,26]. The common initiating factor is the
      tension on the scar, and the critical element needed to counteract this tension
      is scar support. Clinical experience has shown us that the most reliable way to
      support a scar is by using microporous tape. Hydration is a second beneficial
      influence on scar control and is the basis of the use of silicone sheeting and
      gel [7,29,36]. Alpha Centella cream has two main components. The first is an
      extract from the plant Bulbine frutescens. This increases hydration under the
      tape by leaving a layer of fatty vesicles of glycoprotein on the skin surface.
      This also has antibacterial properties. The second component is the principal
      terpenoids extracted from the Centella asiatica plant. These include asiatic
      acid, madecassic acid, and asiaticoside. Centella asiatica has been documented to
      aid wound healing in a large number of scientific reports [5,12,21,22,33,34,40].
      The most beneficial effect appears to be the stimulation of maturation of the
      scar by the production of type I collagen [4,19] and the resulting decrease in
      the inflammatory reaction and myofibroblast production. Thus these components
      have been incorporated into the formulation of a scar management program. This
      publication reviews much of the available literature relating to scar management
      and describes the formulation and use of a scar management program based on this
      information.

PMID- 10890954
TI  - Parotidectomy, a plastic approach.

PMID- 10890955
TI  - The future of imaging in minimally invasive surgery.

PMID- 10890956
TI  - Intracorporeal vs laparoscopic-assisted resection for uncomplicated
      diverticulitis of the sigmoid.
AB  - BACKGROUND: Minimally invasive surgery for uncomplicated diverticulitis of the
      sigmoid (UDS) may be performed either as an intracorporeal procedure (LICR) or as
      laparoscopically assisted colon resection (LACR). METHODS: Prospectively
      collected data of 40 selected patients who had undergone LICR for UDS between
      1992 and 1994 were compared retrospectively with those of 34 diagnosis-matched
      LACR controls operated on at the same hospital between 1995 and 1996 to assess
      the short-term outcome. RESULTS: There were no mortalities. LICR and LACR
      patients were well matched for age, gender, weight, American Society of
      Anesthesiologists (ASA) grade, duration of symptoms, and number of previous
      admissions. There were no significant differences in conversions (one vs three),
      mobilization of splenic flexure (11:29 vs 9:25), anastomotic distance from anal
      verge (12 vs 13 cm), estimated blood loss (270 vs 285 ml), passage of flatus (3.1
      vs 3.8 days), operating room (OR) costs ($3,040 vs $2,820), and total hospital
      costs ($9,250 vs $10, 050) in LICR and LACR patients, respectively. Suprapubic
      skin-incision length (36 vs 60 mm, p << 0.01), size of circular stapler 28:31 mm
      (1:39 vs 6:28, p = 0.03), specimen length (21 vs 11 cm, p << 0.01), complication
      rates (6 vs 5, p = 0.02), OR time (180 vs 244 min, p < 0.001), resumption of oral
      solid food intake (3.2 vs 5.8 days, p < 0.001), hospital stay (4.6 vs 9.9 days, p
      < 0.001), and ward costs ($2,360 vs $4,950, p < 0.001) were significantly
      different in LICR and LACR patients, respectively. CONCLUSION: The immediately
      recognizable advantages of LICR over LACR surmised from this study need further
      evaluation in a prospective randomized setting. LICR remains a procedure of
      considerable technical complexity requiring high surgical skills.

PMID- 10890957
TI  - Laparoscopic treatment of gastric stromal tumors.
AB  - BACKGROUND: The laparoscopic resection of gastric stromal tumors (GST) is being
      performed with increased frequency. METHODS: Between November 1993 and October
      1998, nine consecutive patients with benign and low-grade gastric stromal tumors
      underwent laparoscopic resection using intraoperative endoscopy. For lesions
      located on the anterior wall (three cases), a direct approach was utilized.
      Lesions located on the posterior wall were resected via a transgastric approach
      (four cases) or through a small opening on the omentum or on the gastrocolic
      ligament (two cases). Excision of the lesions was performed manually by means of
      electrocautery and scissors in eight cases; the gastric incisions were closed by
      manual running suture. An endoscopic stapler device was used in one case only.
      RESULTS: All patients were successfully treated laparoscopically; there were no
      conversions to open surgery. Operative time ranged from 75 to 120 min. There was
      one bleeding from the suture line of the gastric wall postoperatively that was
      treated conservatively. The average postoperative hospital stay was 4 days
      (range, 2-6). CONCLUSIONS: In light of the results reported in the literature and
      on the basis of the present work, it seems that laparoscopic resection of GST
      should be considered as the treatment of choice. Wedge resection of anterior wall
      lesions is generally performed. The treatment of posterior wall lesions is still
      controversial. In our opinion the direct approach should be reserved for lesions
      located on the posterior wall of the body, which can be easily reached through
      the greater omentum, while the transgastric approach should be preferred for
      lesions located on the fundus and antrum. Manual excision allows a tailored
      operation; hand-sewn sutures are always feasible, and they are cheaper than
      stapled ones.

PMID- 10890958
TI  - Pediatric laparoscopic splenectomy.
AB  - BACKGROUND: Lateral laparoscopic splenectomy in adults, first reported in 1991,
      was begun with children in 1993. METHODS: The authors reviewed records of 59
      patients 2 to 17 years old who underwent laparoscopic splenectomy by the lateral
      approach between 1994 and 1998 at four medical centers. Patients received
      prophylactic penicillin or vaccinations preoperatively. RESULTS: Of the 59
      patients, 51 required splenectomy for one of the following conditions: idiopathic
      thrombocytopenic purpura, hereditary spherocytosis, or sickle-cell disease.
      Splenomegaly was found in 86% of the patients, and ten accessory spleens were
      resected. No deaths or infection occurred, and only three patients had
      perioperative complications: acute chest crisis, small diaphragmatic injury, and
      intraoperative hemorrhage. One operation was converted to a minilaparatomy
      because of difficulty with specimen extraction. CONCLUSIONS: Pediatric
      laparoscopic splenectomy is safe and effective, resulting in little blood loss,
      rapid recovery, and a good cosmetic outcome.

PMID- 10890959
TI  - A 3-year experience with laparoscopic gastric banding for obesity.
AB  - BACKGROUND: The introduction of laparoscopic techniques-especially that of
      gastric banding-and the fact that conservative management does not provide
      satisfactory long-term results in patients with morbid obesity has resulted in a
      marked increase in the demand for bariatric surgery in our department since 1995.
      In this paper, we present our experience during the first 3 years with this
      approach. METHODS: Data for all patients who had bariatric surgery at our
      institution were collected prospectively. They were analyzed for the purpose of
      this study. RESULTS: A total of 150 patients were operated on between December
      1995 and December 1998 (37 months). There were 130 women and 20 men, with a mean
      age of 37.5 years (range, 19-62). The mean initial excess body weight was 102.9%
      (range, 58-191%), and the mean initial body mass index (BMI) was 44. 6 kg/m(2)
      (range, 35.1-64.1). A Lapband was used in 101 cases and a SAGB in 47 cases. In
      two patients in whom conversion was necessary, we performed a vertical banded
      gastroplasty. Duration of surgery decreased over time from 210 min (first 20
      cases) to 73 min (last 20 cases). Six patients (4%) developed major
      complications, one of whom died. The median duration of postoperative hospital
      stay was 3 days. The mean follow-up was 17 months. In all, 24 patients (16%)
      developed late complications, and 22 (14.6%) required reoperation, mainly for
      band slippage and/or pouch dilatation (14 cases). An incorrect surgical technique
      used for the first 30 patients (Lapband within the lesser sac) was responsible
      for more than half of these complications. The mean excess weight loss was 34% at
      6 months, 55% at 1 year, and 56% at 2 years. Compared to vertical banded
      gastroplasty (197 cases between 1981 and 1995), postoperative morbidity was
      greatly decreased, late morbidity was similar, and weight loss was equivalent.
      CONCLUSIONS: Laparoscopic gastric banding is followed by a weight reduction that
      is similar to that observed after vertical banded gastroplasty, with a much lower
      postoperative morbidity, a shorter hospital stay, and an earlier resumption of
      normal activities. If these results can be confirmed by long-term follow-up,
      laparoscopic gastric banding will be confirmed as the restrictive procedure of
      choice for morbid obesity.

PMID- 10890960
TI  - The role of laparoscopy in the diagnosis and treatment of missed diaphragmatic
      rupture.
AB  - BACKGROUND: Diaphragmatic rupture is one of the most commonly missed injuries in
      trauma cases. Traditionally, laparotomy or thoracotomy has been the treatment of
      choice for this condition. METHODS: During the last 2 years, we treated three
      patients laparoscopically to address neglected diaphragmatic ruptures that caused
      herniation of the intraabdominal contents. RESULTS: In all three cases,
      laparoscopy succeeded in identifying the diaphragmatic defect, so that the
      herniated viscera could be released and the defect repaired primarily or with a
      prosthesis. The intraoperative and the postoperative courses were uneventful;
      there were no significant complications. CONCLUSION: Laparoscopy has an important
      role in the surgical treatment of missed diaphragmatic ruptures.

PMID- 10890961
TI  - Iatrogenic thoracic migration of the stomach complicating laparoscopic nissen
      fundoplication.
AB  - BACKGROUND: Intrathoracic gastric herniation after laparoscopic Nissen
      fundoplication is an uncommon but potentially life-threatening complication that
      may present in the early or late postoperative period. METHODS: A retrospective
      analysis was performed on all patients undergoing antireflux surgery from
      December 1991 to June 1999. RESULTS: Nine cases of gastric herniation occurred
      after 511 operations (0.17%). Patients presented with the condition 4 days to 29
      months after surgery. Eight of these nine patients (89%) had reported vomiting in
      the immediate postoperative period. Seven patients (78%) reported persistent
      odynophagia. A factor common to all patients was that posterior crural repair had
      not been performed. CONCLUSIONS: Measures should be undertaken to prevent
      postoperative vomiting after laparoscopic Nissen fundoplication. Posterior crural
      repair is essential after surgery in all cases.

PMID- 10890962
TI  - Incidence of incipient contralateral hernia during laparoscopic hernia repair.
AB  - BACKGROUND: In addition to its well-known benefits of decreased postoperative
      pain and shorter recovery time, laparoscopic hernia repair has the major
      advantage of allowing the surgeon to explore the side contralateral to the
      clinically diagnosed hernia. The purpose of this study was to evaluate the
      incidence of incipient unsuspected contralateral hernia during totally
      extraperitoneal (TEP) laparoscopic inguinal herniorrhaphy and to analyze the
      risks and benefits of identifying these hernias at the time of the initial
      surgery. METHODS: We did a retrospective review of the charts of all of the 724
      male patients who underwent laparoscopic TEP repair of 958 groin hernias between
      September 1991 and September 1999. The initial clinical impression of the
      existence of unilateral or bilateral hernias was noted and compared to our
      operative findings. The same surgeon performed all the repairs. Exploration of
      the contralateral side was performed in a systematic fashion. A second mesh
      prosthesis was placed if a contralateral hernia was found. RESULTS: Bilateral
      hernia repair was performed on 234 patients (32. 3%). In 62 of them (11.2%), the
      contralateral hernia was diagnosed only at the time of the procedure. Operative
      time ranged from 14 to 185 min (median, 38.6). The operative time for the
      contralateral exploration ranged from 2 to 5 min (median, 2.8). The rate of
      complications was 4.1%, but no complications were directly related to the
      exploration of the asymptomatic side. CONCLUSION: Our study shows that a large
      number of inguinal hernias are undiagnosed by physical examination (11.2%).
      Systematic contralateral exploration using the TEP approach is safe and does not
      greatly increase the operative time. Early identification and repair of a
      contralateral hernia obviates the need for reoperation, reduces overall costs to
      the health care system, and eliminates any further work loss for the patient.

PMID- 10890963
TI  - Gasless endoscopic anterior lumbar interbody fusion utilizing the B. E.R.G.
      approach.
AB  - BACKGROUND: Several authors have reported success using a gas-mediated
      transperitoneal approach for lumbar interbody fusion. However, this approach has
      not been shown to reliably and predictably address segments above L4-5. METHODS:
      The B.E.R.G. approach was attempted in 202 patients who required anterior lumbar
      interbody fusion (ALIF). Of those, 168 were completed successfully without
      conversion to an open procedure. The anterior retroperitoneal approach required
      no gas insufflation. The gasless environment allowed for the use of standard
      anterior instrumentation and a variety of fusion grafts and devices. RESULTS:
      Mean hospital stay was 1.95 days, with 73% of patients discharged in <47 h
      following surgery. Clinical results from the first 50 patients, with a minimum 2
      year follow-up, include a 92% fusion rate and 78% of patients reporting
      significant pain relief of greater than 50%. CONCLUSIONS: The B.E.R.G. approach
      offers significant technical advantages over the standard gas-mediated
      transperitoneal approach for ALIF. The clinical results are similar to those
      reported for open approaches and the gas-mediated transperitoneal approach.

PMID- 10890964
TI  - Incidence and significance of pneumomediastinum after laparoscopic esophageal
      surgery.
AB  - BACKGROUND: Pneumomediastinum can be a sign of esophageal perforation. During
      laparoscopic esophageal surgery, the mediastinum is exposed to carbon dioxide gas
      under pressure that can cause pneumomediastinum. METHODS: Forty-five patients
      undergoing laparoscopic esophageal procedures had erect, inspiratory, single-view
      chest radiographs (CXR) performed in the recovery room (RR). Patients with
      extraabdominal gas underwent daily erect, inspiratory, single-view CXR until
      resorption of the gas or discharge from the hospital. Insufflation time and
      pressure were recorded, and morbidity was evaluated. Results are expressed as
      mean +/- SEM. RESULTS: Twenty-five men (56%)and 20 women (44%) aged 33.0 +/- 2.9
      years underwent 10 Heller myotomies (22.2%), 27 Nissen fundoplications (60.0%),
      six Toupet fundoplications (13.3%), and two paraesophageal hernia repairs (4.4%).
      Twenty-four patients (53.3%) had normal CXR in RR, and 21 (46.7%) had
      extraabdominal gas. Eighteen (85.7%) of the 21 had pneumomediastinum, three
      (14.3%) had pneumothorax, and 12 (57.1%) had subcutaneous emphysema in RR.
      Sixteen of these 21 remained hospitalized and had repeat CXR on postoperative day
      1. Of these 16, five (31.3%) had normal CXR, 11 (68.8%) had pneumomediastinum,
      and seven (43.8%) had subcutaneous emphysema. There were no esophageal
      perforations and no chest tube insertions, and there was no morbidity related to
      pneumomediastinum. CONCLUSION: Pneumomediastinum is observed frequently following
      laparoscopic esophageal operations and often persists past 24 h. After these
      operations, pneumomediastinum is not necessarily indicative of esophageal
      perforation. In this group, it caused no clinically significant events that
      altered the course of the patients.

PMID- 10890965
TI  - Impact of hematological diagnosis on early and late outcome after laparoscopic
      splenectomy: an analysis of 111 cases.
AB  - BACKGROUND: Laparoscopic splenectomy (LS) is now regarded as the treatment of
      choice for autoimmune thrombopenia (ITP). However, there have been few reports
      describing the application of LS to other splenic diseases, such as malignant
      entities and conditions associated with splenomegaly. Hematological diseases have
      specific clinical features that can influence immediate outcome after LS.
      Although the long-term effects of LS are unknown, a risk of splenosis has been
      suggested. Therefore, we designed a study to analyze the impact of primary
      hematological disease on immediate and late outcome in a prospective series of LS
      patients. METHODS: We performed a prospective analysis of 111 LS done between
      February 1993 and March 1999. The patients were classified by hematological
      indications into the following four groups: (a) group 1, low platelet count. This
      group was further subdivided into group 1A, idiopathic thrombocytopenic purpura
      (ITP) (n = 48) and group 1B, HIV-related ITP (n = 8); (b) group 2, anemia. This
      group was further subdivided into group 2A, autoimmune hemolytic anemia (n = 8),
      and group 2B, spherocytosis (n = 11); (c) group 3, malignancy (n = 28); and (d)
      group 4, others (n = 8). Immediate outcomes were recorded prospectively.
      Hematological status and late complications were reviewed after a mean follow-up
      of 24 +/- 18 months. RESULTS: There were no significant differences between the
      groups in terms of conversion, transfusion requirements, and morbidity, although
      transfusion and morbidity were slightly higher in group 3. However, hospital stay
      was significantly longer in groups 3 and 4 than in groups 1 and 2. Long-term
      follow-up showed satisfactory hematological results in >/=75% of patients (group
      1A, 82%; group 1B, 88%; group 2A, 88%; group 2B, 100%; group 3, 75%; group 4,
      88%). Overall, late morbidity was 8.3% and mortality was 6.2%, mainly due to
      deaths in group 4 (six of 22 patients). CONCLUSION: LS is a safe and reproducible
      procedure for most hematological indications, with a similar immediate outcome
      for benign diseases and a long-term hematological response comparable to the
      standard results that have been observed in open series.

PMID- 10890966
TI  - Short- and long-term results after laparoscopic vs conventional colon resection
      in a tumor-bearing small animal model.
AB  - BACKGROUND: We designed a study to evaluate the short- and long-term outcome of
      laparoscopic vs conventional colonic resection in a tumor-bearing small animal
      model. METHODS: We operated on male BD X rats (260-300 g), performing either
      laparoscopic (n = 9) or open colon resection (n = 9) in order to evaluate stress
      and immunological response to laparoscopic vs conventional colon resection. A
      third group (n = 9) underwent anesthesia only. Immediately before and after
      surgery, as well as at 1, 7, and 21 days postoperatively, a sample of 1 ml blood
      was taken from the retrobulbar venous plexus. Stress (corticosterone) and immune
      parameters (neopterine and IL-1 beta, IL-6) and body weight as a parameter of
      postoperative recovery were measured to identify short-term alterations. Long
      term changes were evaluated in terms of survival time and at autopsy by measuring
      the tumor weight and the number of tumor infiltrated nodules (histology).
      RESULTS: The analysis of variance (ANOVA) showed significant differences between
      the three groups over a period of 1 week (p < 0.001 for corticosterone, p = 0.009
      for neopterine, p = 0.04 for IL-1 beta, p = 0.024 for IL-6). Additionally,
      significant differences by t-test were found between the laparoscopic (minor
      alteration) and conventional (major alteration) group regarding corticosterone (p
      = 0.0015), neopterine (p = 0.0024), IL 1-beta (p = 0.033), and IL-6 (p = 0.015)
      at the end of the operation. One week after the operation, the body weight was
      different depending on the type of operative procedure: 7 days postoperatively
      the rats lost 8% of their body weight after open surgery but only 4.3% after
      laparoscopic surgery. After anesthesia only, body weight increased by
      approximately 4.8%. The medium survival time for the lap group was 44 days,
      whereas it was 44.1 days for the conventional group and 46 days for the
      anesthesia group (ANOVA p = 0.625). The number of nodules was 13.5 in the
      laparoscopic group 10.5 in the open group, and 7.4 in the anesthesia group,
      (ANOVA p = 0.119). The tumor weight was 6.8 g in the laparoscopic group, 6.4 g in
      the open group, and 5.04 g in the anesthesia group (ANOVA p = 0.874). CONCLUSION:
      In a tumor-bearing small animal model, laparoscopic colon resection alters the
      stress and immune system less than open colon resection. This observation has no
      implications for the long-term results as measured by survival time and at
      autopsy. Therefore, laparoscopic colon resection has a short-term benefit and has
      no negative effect on long-term results compared to conventional operative
      procedures.

PMID- 10890967
TI  - Short-stay laparoscopic adrenalectomy.
AB  - BACKGROUND: We performed a consecutive series of unilateral laparoscopic
      adrenalectomies (LA) with the expectation of short (less than 24 h) hospital
      stay. Results were compared with those from laparoscopic cholecystectomy (LC) and
      unilateral open adrenalectomy (OA). METHODS: A combination of chart review and
      patient questionnaires was used to compare LA (n = 19) to LC (n = 20) regarding
      length of stay (LOS), narcotic requirements, and time to full recovery. Chart
      reviews also were used to compare LA to OA (n = 48) regarding operating room time
      (OR time), LOS, and surgical morbidity. RESULTS: All of the LC patients as
      compared with 47% of the LA patients were discharged within 24 h. The reason for
      additional hospitalization in the LA group was pain control. After discharge, the
      narcotic requirement lasted 6.6 days in the LA group as compared with 3.4 days in
      the LC group (p < 0.01), but the times until full recovery were not significantly
      different (12.2 vs 11.3 days respectively). Operating room times did not differ
      significantly between the LA and OA groups (3.3 and 3.8 h, respectively), but
      there were fewer postoperative complications and much shorter LOS in the LA group
      (1.5 vs 6.3 days; p < 0.001), a difference that remained significant even when
      cases from the same time period were compared. CONCLUSIONS: Increased pain in LA
      as compared with LC patients may result in a slightly longer LOS and higher
      narcotic requirement during the early postoperative period, but time to full
      recovery between the two groups is the same. As compared with its open
      counterpart, LA offers a significant reduction in LOS and morbidity with no
      increase in OR time.

PMID- 10890968
TI  - Axilloscopy and endoscopic sentinel node detection in breast cancer patients.
AB  - BACKGROUND: Sentinel node biopsy is a promising technique that allows the
      axillary status of breast cancer patients to be predicted with high accuracy.
      Reducing false negative results remains a major challenge for the improvement of
      this procedure. Furthermore, new techniques are required to achieve axillary
      clearing with less morbidity in cases of unsuccessful mapping or multicentric
      carcinoma. We analyzed whether axilloscopy and endoscopic sentinel node biopsy is
      a feasible procedure for visualization of the axillary space and resection of the
      sentinel node using endoscopic techniques. METHODS: Following blue dye-guided
      lymphography and liposuction of the axillary fat, endoscopic axillary sentinel
      node biopsy was performed in 35 breast cancer patients. We then assessed the
      exposure of anatomical landmarks, the detection rate of the sentinel node, the
      false negative rate, and the accuracy of consecutive axillary clearing. RESULTS:
      In almost every case, an excellent anatomical orientation was achieved. The
      detection rate for the sentinel node was 83.3%. In one case, the sentinel node
      did not reflect the status of the residual axilla. A mean number of 17.1 lymph
      nodes was harvested at consecutive axillary clearing. CONCLUSIONS: Axilloscopy
      and endoscopic sentinel node biopsy, following liposuction of the axillary fat,
      is a feasible procedure that allows identification and minimally invasive
      resection of the sentinel node with high accuracy. The endoscopic approach might
      help to minimize the pitfalls of sentinel node biopsy by visualizing the axillary
      space. In future, it may become a technique that enables minimally invasive
      axillary clearing when complete lymphadenectomy is required.

PMID- 10890970
TI  - Technique and early results of outpatient laparoscopic mesh onlay repair of
      ventral hernias.
AB  - BACKGROUND: This report describes the technique and early results of a simple
      outpatient laparoscopic ventral hernia repair. METHODS: Data were gathered
      prospectively for all laparoscopic ventral hernia repairs from January 1996 to
      December 1997 at a 228-bed hospital. Prolene mesh was stapled to the peritoneal
      surface of the abdominal wall, leaving sac in situ and mesh uncovered. Patients
      were seen by the operating surgeon within 2 months, and by an impartial surgeon
      (J.S.) after 3 to 14 months (average, 7 months; median, 6 months). RESULTS:
      Repairs involved 44 hernias with orifice sizes 2 to 20 cm in diameter, and an
      average area of 20 cm(2). Of these 44 hernias, 36 were postoperative and 8
      primary. Furthermore, 20% were recurrent hernias. There were four conversions.
      The outpatient rate was 98%, with one readmission for ileus. The early recurrence
      rate was 5%. CONCLUSIONS: Laparoscopic mesh onlay repair is a safe, easy, and
      effective procedure with minimal discomfort and a low early recurrence rate that
      can be performed safely on an outpatient basis.

PMID- 10890971
TI  - Laparoscopically assisted ventriculoperitoneal shunt placement using 2-mm
      instrumentation.
AB  - BACKGROUND: Laparoscopy has potential benefit in the placement of
      ventriculoperitoneal shunts. In patients who have undergone multiple shunt
      revisions or other abdominal operations, laparoscopy may be particularly
      beneficial when finding of a suitable area in which to place the shunt is a
      concern. The purpose of this study was to evaluate the safety and effectiveness
      of laparoscopically assisted ventriculoperitoneal shunt placement, with an
      emphasis on using 2-mm instrumentation. METHODS: Laparoscopically assisted
      ventriculoperitoneal shunt placement using 2-mm instrumentation was performed in
      eight adult hydrocephalus patients from August 1996 to September 1998. All eight
      patients had undergone 1 to 18 prior shunt revisions. The procedures were
      performed with two 2-mm trocars. The instrumentation consisted of a 2-mm
      laparoscope, a 2-mm grasper, and 2-mm scissors. All shunts were placed in an area
      free of adhesions and checked for flow under direct vision. Four of the patients
      required a lysis of adhesions to create a space adequate for catheter placement.
      RESULTS: All of the procedures were successful, with no operative complications.
      The operative times ranged from 29 to 99 min, (mean, 63 min). The blood loss in
      all of the procedures was minimal. At this writing, none of the patients have
      required subsequent distal shunt revisions. No conversions to larger instruments
      or an open procedure were required. CONCLUSIONS: Laparoscopically assisted
      ventriculoperitoneal shunt placement using 2-mm instrumentation is safe and
      effective, offering several advantages over the open procedure. This procedure is
      ideal for the use of 2-mm instruments.

PMID- 10890969
TI  - The influence of different insufflation pressures during carbon dioxide
      pneumoperitoneum on the development of pulmonary metastasis in a mouse model.
AB  - BACKGROUND: The effects of different insufflation pressures on the development of
      pulmonary metastasis was investigated in a mouse laparoscopy model. METHODS:
      BALB/C mice intravenously inoculated with colon 26 cells were randomized to one
      of five treatment groups (10 mice per group): pneumoperitoneum at different
      pressures of 5, 10 or 15 mmHg; full laparotomy for 60 min; or anesthesia control.
      Cancer nodules on the lung surface 19 days postoperatively were compared between
      groups. RESULTS: (a) As compared with the control group, pneumoperitoneum at 10
      and 15 mmHg and laparotomy enhanced the growth of pulmonary metastases (p <
      0.01). (b) The growth of metastases also was greater in laparotomy group mice
      than in mice undergoing pneumoperitoneum at 5 and 10 mmHg (p < 0.05).
      CONCLUSIONS: These results suggest that the effects of different insufflation
      pressures on the growth of pulmonary metastases are not identical, and that
      pneumoperitoneum with high pressure may promote pulmonary metastases similar to
      those with laparotomy.

PMID- 10890972
TI  - Bougienage and balloon dilation using a conventional tracheal tube for
      tracheobronchial stenosis before stent placement.
AB  - In order to achieve urgent restoration of the airways in tracheobronchial
      stenosis and to make stent placement simpler and safer, we developed a method
      that allows combined bougienage and balloon dilation via the use of a
      conventional tracheal tube. Fifteen patients with tracheobronchial stenosis
      underwent bougienage and balloon dilation using a tracheal tube with a cuff
      attached, inserted via a tracheostomy, before stent placement. The conventional
      tracheal tube was inserted via a tracheostomy, the cuff was expanded at the
      stenotic site, and the tube was fixed to the tracheostomy and left in place for a
      few days until sufficient dilation was achieved. This procedure was conducted on
      the trachea in 10 patients, the left main bronchus in three patients, and the
      right main bronchus in two patients. In all patients, the procedure immediately
      relieved the obstructive symptoms and dilated the stenosis sufficiently.
      Thereafter, Dumon stents were inserted in 10 patients, dynamic stents in four
      patients, and an expandable metallic stent in one patient. The stents were
      introduced easily with no other dilation procedure after a mean of 5 days from
      the start of the procedure. For tracheobronchial stenosis, bougienage and balloon
      dilation using a tracheal tube with an integral cuff via a tracheostomy is a
      simple and safe method for achieving both urgent relief of airway stenosis and
      dilation before stent placement.

PMID- 10890974
TI  - Hemodynamic consequences of high- and low-pressure capnoperitoneum during
      laparoscopic cholecystectomy.

PMID- 10890975
TI  - The authors reply.

PMID- 10890976
TI  - An efficient technique for splenic pedicle retraction.

PMID- 10890978
TI  - Mouse paraxial protocadherin is expressed in trunk mesoderm and is not essential
      for mouse development.
AB  - Paraxial protocadherin (PAPC) is a cell adhesion molecule that marks cells
      undergoing convergence-extension cell movements in Xenopus and zebrafish
      gastrulating embryos. Here a mouse homologue (mpapc) was identified and
      characterized. During early- to mid-gastrulation, mpapc is expressed in the
      primitive streak as the trunk mesoderm undergoes morphogenetic cell movements. At
      head-fold stage mpapc expression becomes localized to paraxial regions in which
      somites are formed in the segmental plate. At later stages, mpapc displays a
      complex expression pattern in cerebral cortex, olfactory bulb, inferior
      colliculus, and in longitudinal stripes in hindbrain. To analyze the effect of
      the loss of PAPC function during mouse development, a null allele of the mouse
      papc gene was generated. Homozygous animals show no defects in their skeleton and
      are viable and fertile.

PMID- 10890979
TI  - Expression of the otx gene in the ciliary bands during sea cucumber
      embryogenesis.
AB  - The Otx gene encodes a homeodomain transcription factor that has a highly
      conserved role in brain formation of both flies and vertebrates. To deduce
      evolutionary relationship of the chordate central nervous system to the larval or
      adult nervous system of nonchordate deuterostomes, we characterized the
      expression of the Otx gene (Sj-Otx) throughout the entire embryonic and larval
      development of the sea cucumber Stichopus japonicus. Sj-Otx transcripts were
      detected in fertilized eggs and in the posterior part of the archenteron of
      gastrulae. However, the expression was downregulated as embryos developed into
      auricularia larvae. Sj-Otx was expressed again in the ciliary bands of late
      auricularia larvae, just before metamorphosis to doliolaria larvae. The
      expression domain corresponded to the domains moving to the mouth during
      metamorphosis and sinking into the buccal cavity, but not to the five transverse
      ciliary bands of the doliolaria. The expression gradually disappeared during
      further development and was not detected in juveniles. These results indicate
      that the gene responsible for chordate brain formation is expressed in the
      ciliary bands of auricularia larvae.

PMID- 10890980
TI  - Mouse fzd4 maps within a region of chromosome 7 important for thymus and cardiac
      development.
AB  - The cardiac neural crest (CNC) plays a central role in development of the thymus
      gland and cardiovascular system. Through morphological and histological
      characterization of embryos homozygous for the Del(7)Tyr(c-112K) and Del(7)Tyr(c
      3H) albino deletions, we identified abnormalities that are consistent with
      aberrant development of tissues requiring CNC contributions. The defects include
      incompletely penetrant heart and great vessel patterning defects and hypoplastic
      thymus glands. The CNC phenotype is complemented by the partially overlapping
      deletion Del(7)Tyr(c-23DVT). Combined, these results suggest that a functional
      region necessary for development of CNC derived tissues is located between the
      Del(7)Tyr(c-23DVT) and Del(7)Tyr(c-112K) distal deletion breakpoints. This
      interval encompasses a functional region previously identified as important for
      juvenile survival (juvenile development and fertility, jdf). Using deletion
      mapping, we localized the Frizzled4 (Fzd4) gene to the jdf/thymus and cardiac
      development intervals.

PMID- 10890982
TI  - Forkhead Foxe3 maps to the dysgenetic lens locus and is critical in lens
      development and differentiation.
AB  - Here we report the isolation of a novel forkhead gene, Foxe3, that plays an
      important role in lens formation. During development Foxe3 is expressed in all
      undifferentiated lens tissues, and is turned off upon fiber cell differentiation.
      Foxe3 maps to a chromosomal region containing the dysgenetic lens (dyl) mutation.
      Mice homozygous for dyl display several defects in lens development. dyl mice
      also show altered patterns of crystallin expression suggesting a dysregulation of
      lens differentiation. We have identified mutations in Foxe3 that cosegregate with
      the dyl phenotype and are a likely cause of the mutant phenotype. Head ectoderm
      expression of Foxe3 is absent in Rx-/- and Small eye embryos indicating that Rx
      and Pax6 activity are necessary for Foxe3 expression.

PMID- 10890981
TI  - Micro-capillary tube in situ hybridisation: a novel method for processing small
      individual samples.
AB  - We have developed a strategy to individually analyse large numbers of small
      tissue samples by RNA in situ hybridisation. Samples of approximately 0.4 mm x
      0.5 mm are processed in rectangular capillary tubes fitted with nylon mesh and
      glass beads using standard protocols. Eighteen samples can be assayed
      simultaneously without loss, and background is low. Specifically, mouse Sox2 RNA
      expression is examined in the chorion of extraembryonic tissue of 7.5 days post
      coitum embryos. This technique works equally well for double RNA labelling and
      could potentially be used for antibody staining of proteins.

PMID- 10890983
TI  - Banish the restrictive covenant!

PMID- 10890984
TI  - A case of angiolymphoid hyperplasia with eosinophilia treated with intralesional
      interferon alfa-2a.

PMID- 10890985
TI  - A comparison of 3 lasers and liquid nitrogen in the treatment of solar
      lentigines: a randomized, controlled, comparative trial.
AB  - OBJECTIVE: To determine if laser therapy is superior to liquid nitrogen for the
      treatment of solar lentigines and if so, to determine if one laser is superior to
      the other lasers that were tested. DESIGN: Randomized, controlled, comparative
      study with blinded observers. SETTING: University-based dermatology clinic.
      PARTICIPANTS: Twenty-seven patients with multiple solar lentigines on the backs
      of both hands. INTERVENTIONS: Liquid nitrogen cryotherapy, the Medlite II
      frequency-doubled Q-switched Nd:YAG laser (Continuum Biomedical, Livermore,
      Calif), the HGM K1 krypton laser (HGM Medical Laser Systems Inc, Salt Lake City,
      Utah), and the DioLite 532-nm diode-pumped vanadate laser (Iridex Corp, Mountain
      View, Calif). MAIN OUTCOME MEASURES: Photographs of the hands were taken prior to
      and 6 and 12 weeks following treatment. Blinded observers and patients evaluated
      each treatment on its ability to lighten pigmented lesions without causing
      unwanted adverse effects. RESULTS: Many new laser systems claim an advantage for
      treating pigmented lesions by selectively destroying melanin. In this study, the
      frequency-doubled Q-switched Nd:YAG laser was most likely to provide significant
      lightening (P<.05), followed by the HGM K1 krypton laser, the 532-nm diode-pumped
      vanadate laser, and liquid nitrogen. The frequency-doubled Q-switched Nd:YAG
      laser also had the fewest adverse effects (P<.05), while the HGM K1 krypton laser
      had the most (P<.05). Of the 27 patients, 25 preferred laser therapy to
      cryotherapy, with the frequency-doubled Q-switched Nd:YAG laser being the most
      popular. CONCLUSIONS: Laser therapy is superior to liquid nitrogen for the
      treatment of solar lentigines. Of the laser systems tested in this study, the
      frequency-doubled Q-switched Nd:YAG laser is the most effective.

PMID- 10890986
TI  - Antibiotic rashes in children: a survey in a private practice setting.
AB  - OBJECTIVE: To document the frequency and severity of various types of rashes seen
      with commonly used oral antibiotics in the pediatric outpatient setting. DESIGN:
      A retrospective review of 5923 patient records at a pediatric office. SETTING: A
      private group pediatric practice in northern Virginia with about 12,000
      registered active patients. PATIENTS AND METHODS: Approximately 50% of the clinic
      medical records were reviewed. All children (defined as those aged 0-18 years in
      this study) identified on their medical records as having developed a rash
      following treatment with 1 or more of the commonly used oral antibiotics were
      included in the study. For further validation, a questionnaire about parental
      recollection of description of rash, other associated symptoms, physician
      verification, and outcome was mailed to families with children designated as
      being allergic to an antibiotic. RESULTS: On a prescription basis, significantly
      more rashes were documented for cefaclor (4.79%) compared with penicillins
      (2.72%), sulfonamides (3. 46%), and other cephalosporins (1.04%). Based on the
      number of patients for whom each group of antibiotic was prescribed, the
      documented frequencies of rashes were 12.3%, 7.4%, 8.5%, and 2.6% for cefaclor,
      penicillins, sulfonamides, and other cephalosporins, respectively. None of the
      children had rashes severe enough to require hospitalization. CONCLUSIONS: In a
      review of almost 6000 records in a private pediatric primary care setting, rashes
      occurred in 7.3% of children who were given the commonly used oral antibiotics.
      Significantly more rashes were documented with cefaclor use than with use of any
      of the other oral antibiotics.

PMID- 10890987
TI  - A comparison of multilayer bandage systems during rest, exercise, and over 2 days
      of wear time.
AB  - OBJECTIVE: To study the interface pressure between the leg and 8 different
      multilayer bandage systems during postural changes, exercise (walking), and over
      2 days of wear time. DESIGN: Comparison of 8 different compression bandages under
      standardized conditions. SETTING: Department of Dermatology, University Hospital
      of Zurich, Zurich, Switzerland. PARTICIPANTS: A series of 10 healthy volunteers,
      5 females and 5 males, aged 26 to 65 years. INTERVENTION: An electropneumatic
      device was used to measure interface pressure at 12 points of the leg. MAIN
      OUTCOME MEASURES: (1) Pressure changes from the standing to the sitting and
      supine position at rest, (2) pressure amplitude during exercise (200-m treadmill
      walk at 3.2 m/s, 0 degrees incline), and (3) pressure decrease over 2 days of
      wear time. RESULTS: Results are given as median with the 10% to 90% confidence
      intervals. Multilayer bandages of short and medium stretch showed a larger
      pressure decrease when the patient was supine (eg, 3 short stretch bandages: 18.0
      mm Hg [reference range, 15.5-19.5 mm Hg]) than systems of medium and long stretch
      bandages (eg, 4-layer bandage, 6.0 mm Hg [reference range, 4.5-7.0 mm Hg])
      (P=.005). The amplitude of pressure waves during exercise was comparable among
      most multilayer bandage systems. The pressure loss over time was the smallest in
      elastic bandages (eg, 4-layer bandage, 6.0 mm Hg [reference range, 0.0-10.5 mm
      Hg]), compared with short stretch bandages (eg, 3 short stretch bandages, 18.0 mm
      Hg [reference range, 16.5-20.5 mm Hg]) (P=.005). CONCLUSIONS: Highly elastic
      multilayer bandage systems showed the smallest pressure loss over several days,
      but the small pressure decrease when the patient was supine makes them
      potentially hazardous to patients with arterial occlusive disease. Short stretch
      bandages and the Unna boot with an inelastic zinc plaster bandage generate large
      pressure waves while walking and showed a marked pressure decrease when the
      patient was supine, but they lose a lot of their pressure within the first hours
      of wear. Multilayer systems composed of short stretch and cohesive medium stretch
      bandages represent a good compromise between elastic and inelastic bandage
      systems (moderate pressure loss over time, large pressure decrease on lying
      down). The clinical effectiveness of the different types of compression still
      remains to be studied.

PMID- 10890988
TI  - Ineffectiveness of cyclosporine as an adjuvant to corticosteroids in the
      treatment of pemphigus.
AB  - OBJECTIVE: To compare the effectiveness and the adverse effects of 2 different
      regimens for the treatment of pemphigus: corticosteroids alone compared with a
      combination of corticosteroids and cyclosporine. DESIGN: Concurrently randomized
      trial. SETTING: Tertiary care medical center. PATIENTS AND METHODS: We studied 33
      sequential hospitalized patients with newly diagnosed pemphigus vulgaris (n=29)
      or pemphigus foliaceous (n=4) based on clinical, histological, and
      immunofluorescence criteria who had not previously been treated with systemic
      corticosteroids or immununosuppressive drugs. Patients were randomly assigned to
      treatment with methylprednisolone or prednisolone plus cyclosporine.
      INTERVENTION: Both groups were treated with similar initial doses of prednisolone
      (prednisone equivalent, 1 mg/kg), which were increased 50% every 5 to 10 days
      based on persistence of disease activity. One group was treated in addition with
      cyclosporine (5 mg/kg). MAIN OUTCOME MEASURES: Patients were followed up closely
      for clinical outcome based on time required to control active manifestations of
      the disease, induction of partial and complete remissions, total amount of
      corticosteroids administered, frequency of relapses, and development of
      complications. RESULTS: The 2 groups were similar in terms of demographics and
      baseline disease severity. There was no difference between groups in any of the
      variables used to measure response to treatment or total amount of
      corticosteroids administered. Complications were more common in patients who
      received combination therapy. CONCLUSION: Combination treatment with
      corticosteroids and cyclosporine, 5 mg/kg, offers no advantage over treatment
      with corticosteroids alone in patients with pemphigus.

PMID- 10890989
TI  - Neonatal and infantile erythrodermas: a retrospective study of 51 patients.
AB  - OBJECTIVE: To determine the frequency of the various underlying causes of
      erythroderma in newborns or infants, as well as which clinical or laboratory
      findings were relevant for the etiological diagnosis. PATIENTS: Fifty-one
      patients who presented with exfoliative erythroderma during their first year of
      life were included in this retrospective study. SETTING: Department of Pediatric
      Dermatology at a university hospital. RESULTS: On average, the etiological
      diagnosis was established 11 months after the onset of erythroderma. The
      underlying causes observed included immunodeficiency (30%), simple or complex
      ichthyosis (24%), Netherton syndrome (18%), and eczematous or papulosquamous
      dermatitis (20%). Five patients (10%) had erythroderma of unknown origin. The
      following parameters were of value in determining the underlying cause of
      erythroderma: congenital onset, skin induration and the presence of large scaling
      plaques, alopecia with or without hair dysplasia, evolution, response to topical
      corticosteroid therapy, presence of infections, and failure to thrive.
      Histological analysis confirmed the diagnosis in only 19 (45%) of 42 cases.
      However, it proved of great value for the detection of significant lymphocyte
      infiltration or keratinocyte necrosis indicating a diagnosis of Omenn syndrome or
      immunodeficiency. The prognosis was poor in this series: the mortality rate was
      16%, and severe dermatosis persisted in 29 (67%) of the survivors. CONCLUSIONS:
      The etiological diagnosis of neonatal erythroderma is difficult to make; some
      clinical features may be helpful, but no one feature is characteristic of a
      cause. An immunodeficiency must be suspected in cases of severe erythroderma with
      skin induration, severe alopecia, failure to thrive, infectious complications, or
      evocative histological findings. The prognosis is poor, with a high rate of
      mortality in immunodeficiency disorders and severe chronic disease in Netherton
      syndrome and psoriasis.

PMID- 10890990
TI  - Cutaneous involvement in patients with angioimmunoblastic lymphadenopathy with
      dysproteinemia: a clinical, immunohistological, and molecular analysis.
AB  - OBJECTIVE: To determine whether cutaneous involvement in patients with
      angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is related to a
      clonal T-cell proliferation. DESIGN: Retrospective study. SETTING: University
      hospitals. PATIENTS: Ten patients with AILD and cutaneous involvement. MAIN
      OUTCOME MEASURE: The T-cell receptor-gamma (TCRG)gene rearrangement was studied
      with the use of polymerase chain reaction and denaturing gradient gel
      electrophoresis in blood, nodal, and skin samples. Skin and nodal samples were
      investigated also for the presence of Epstein-Barr virus (EBV) RNA by in situ
      hybridization. RESULTS: A transient morbilliform eruption of the trunk was seen
      most often. Other cutaneous features were infiltrated plaques and purpuric or
      urticarial lesions. A clonal TCRG gene rearrangement was detected in 7 skin
      samples, corresponding to a maculopapular eruption with a histological pattern of
      nonspecific mild lymphoid dermal infiltrate in 6 patients, and to erythematous
      plaques with histological findings of typical cutaneous lymphoma in 1 patient. In
      the 5 patients in whom a TCRG gene rearrangement was evidenced in skin and lymph
      node samples, identical clones were detected in both. Five patients died by the
      end of the study, with a mean survival of 33.2 months. Four of these 5 patients
      had a clonal infiltrate in skin and lymph nodes. The EBV RNA was detected in only
      1 of 10 skin biopsy specimens and in 5 of 8 lymph nodes tested. CONCLUSIONS:
      Cutaneous involvement is often related to a clonal T-cell proliferation in AILD,
      even when clinical and histological features are nonspecific. Cutaneous
      infiltrate seems to be clonally related to the nodal T-cell proliferation. The
      role of EBV infection in skin lesions was not evidenced.

PMID- 10890991
TI  - Cytophagic histiocytic panniculitis and subcutaneous panniculitis-like T-cell
      lymphoma: report of 7 cases.
AB  - BACKGROUND: Cytophagic histiocytic panniculitis (CHP) is a rare subtype of
      panniculitis that usually follows a fatal course, with a terminal hemophagocytic
      syndrome. Recent reports on a subset of peripheral T-cell lymphoma named
      subcutaneous panniculitis-like T-cell lymphoma (SPTL) raised the question about
      the relationship between these entities. OBSERVATIONS: We describe 7 patients in
      the study: 1 with fatal CHP, 4 with SPTL, and 2 with long-term CHP. The 5
      patients with fatal CHP and SPTL died of complications of hemophagocytic
      syndrome, with a disease duration ranging from 8 to 74 months. The other 2
      patients were still alive 6 and 41 years after disease onset. Immunohistochemical
      results proved that 2 of the SPTL cases were type alpha/beta and expressed the
      cytotoxic/suppressor antigen CD8, while the other 2 were type gamma/delta and
      were positive for the natural killer-associated antigen CD56. In these 4 cases,
      molecular biology studies by polymerase chain reaction detected T-cell receptor
      gamma gene rearrangement, indicating a clonal process. In contrast, in the 2
      patients who had long-term CHP, the polymerase chain reaction results failed to
      disclose clonality. In the subject with fatal CHP, genotypic analysis was not
      performed. CONCLUSION: Our observations suggest that CHP and SPTL may span a
      clinicopathologic spectrum in which there is a natural disease progression from
      CHP to SPTL.

PMID- 10890992
TI  - Acquired port-wine stains and antecedent trauma: case report and review of the
      literature.
AB  - BACKGROUND: While cases of congenital port-wine stains (PWSs) are relatively
      common, cases of acquired PWSs are quite rare. Many of the reported cases of the
      acquired type have been reported to be related to previous trauma. OBSERVATIONS:
      We encountered a case of acquired PWSs in a 3-year-old girl. Her parents noted
      that the lesions appeared in areas of antecedent trauma. This prompted us to
      review all reported cases of acquired PWSs and to assess the relationship to
      trauma. Among the 59 cases reported, there was a slight female predominance
      (female-male ratio, 35:24). Seventeen (29%) of the cases were related to trauma.
      One report evaluated the effectiveness of lasers in the treatment of acquired
      PWSs and found that 54% of patients treated with pulsed dye lasers had an
      excellent response or complete clearance. CONCLUSIONS: Port-wine stains are not
      only congenital but can be acquired as well. Trauma can be one of the causes of
      acquired PWSs. To explain this phenomenon, various theories, including abnormal
      vascular repair and altered vascular innervation, have been proposed. Lasers are
      the treatment of choice in all cases of PWSs and may be more effective in those
      that are acquired.

PMID- 10890993
TI  - Benign cutaneous vascular tumors of infancy: when to worry, what to do.
AB  - OBJECTIVES: To discuss the current knowledge regarding complicated hemangiomas
      (cervicofacial, periorbital, lumbosacral, and parotid), including the associated
      syndromes of diffuse neonatal hemangiomatosis and PHACES (posterior fossa
      malformations, most commonly of the Dandy-Walker variant; hemangiomas [especially
      large, plaquelike, facial lesions]; arterial anomalies; cardiac anomalies and
      coarctation of the aorta; eye abnormalities; and sternal cleft and/or
      supraumbilical raphe). To discuss 2 newly recognized entities that may be a
      source of diagnostic confusion with the common hemangioma, the kaposiform
      hemangioendothelioma and tufted angioma. To discuss the risks and benefits of
      current treatment options, including the use of systemic corticosteroids and
      interferon in necessary situations. DATA SOURCES: The pertinent world literature
      was reviewed and incorporated into experience from our pediatric dermatology
      practice at the University of Texas Medical School at Houston. CONCLUSIONS: The
      common hemangioma, kaposiform hemangioendothelioma, and tufted angioma, though
      benign histologically, may cause serious consequences for children.
      Dermatologists should be able to recognize unique clinical presentations of these
      lesions and obtain further diagnostic evaluation accordingly. Dermatologists
      should also be aware of available treatment options, including the use of
      systemic chemotherapy in life-threatening situations.

PMID- 10890994
TI  - Laser treatment of pigmented lesions--2000: how far have we gone?

PMID- 10890995
TI  - Cytophagic histiocytic panniculitis--a critical reappraisal.

PMID- 10890996
TI  - A long-standing dermal nodule on the neck of a young woman. Diagnosis:
      bronchogenic cyst.

PMID- 10890997
TI  - Severe nail dystrophy associated with painful fingertips. Diagnosis: psoriatic
      onychopachydermoperiostitis (POPP).

PMID- 10890998
TI  - Chronic pustular eruption of the thumbs. Diagnosis: acrodermatitis continua of
      Hallopeau (ACH).

PMID- 10890999
TI  - Multiple annular plaques on the face of a middle-aged woman. Diagnosis: secondary
      syphilis.

PMID- 10891000
TI  - Is pityriasis rosea skin healthier than healthy skin?

PMID- 10891001
TI  - Is pityriasis rosea skin healthier than healthy skin?

PMID- 10891002
TI  - Tumor screening and biology in malignant melanomas.

PMID- 10891003
TI  - An alternate explanation for the increase in the incidence of melanoma being
      restricted to patients with thin lesions.

PMID- 10891004
TI  - An alternate explanation for the increase in the incidence of melanoma being
      restricted to patients with thin lesions

PMID- 10891005
TI  - Treatment of labial lentigos in atopic dermatitis with the frequency-doubled Q
      switched Nd:YAG laser.

PMID- 10891006
TI  - Expression of beta-catenin, a key mediator of the WNT signaling pathway, in basal
      cell carcinoma.

PMID- 10891007
TI  - Should dermatologists go public? A skin cancer screening campaign at recreation
      centers.

PMID- 10891008
TI  - Onychomycosis treated until the nail is replaced by normal growth or there is
      failure.

PMID- 10891009
TI  - The "wobble sign" in epiluminescence microscopy as a novel clue to the
      differential diagnosis of pigmented skin lesions.

PMID- 10891013
TI  - News and notes: july 2000

PMID- 10891010
TI  - High-fluence modified pulsed dye laser photocoagulation with dynamic cooling of
      port-wine stains in infancy.

PMID- 10891014
TI  - Constancy and Change.

PMID- 10891015
TI  - Use of seclusion and restraint in children and adolescents. Council on Scientific
      Affairs, American Medical Association.

PMID- 10891016
TI  - A randomized controlled study on the effectiveness of a multifaceted intervention
      program in the primary prevention of asthma in high-risk infants.
AB  - BACKGROUND: The prevalence of asthma has increased in developed countries in the
      past 2 decades. The effectiveness of intervention measures on the primary
      prevention of asthma has not been well studied. OBJECTIVE: To assess the
      effectiveness of a multifaceted intervention program in the primary prevention of
      asthma in high-risk infants (in this study, infants are defined as persons from
      birth to the age of 1 year). DESIGN: Prospective, prenatally randomized,
      controlled study with follow-up through the age of 1 year. SETTING: University
      hospital-based settings at 2 Canadian centers: Vancouver, British Columbia, and
      Winnipeg, Manitoba. PARTICIPANTS: A total of 545 high-risk infants (at least 1
      first-degree relative with asthma or 2 first-degree relatives with other IgE
      mediated allergic diseases) identified before birth. INTERVENTIONS: Avoidance of
      house dust mite and pet allergens and environmental tobacco smoke, encouragement
      of breastfeeding, and supplementation with a partially hydrolyzed formula. MAIN
      OUTCOME MEASURES: Probable or possible asthma, rhinitis without apparent colds,
      and a prick skin test result positive for common inhalant allergens. RESULTS:
      Thirty-eight (15.1%) of the 251 infants available for assessment in the
      intervention group and 49 (20.2%) of the 242 infants available for assessment in
      the control group fulfilled the criteria for possible or probable asthma
      (adjusted relative risk, 0.66; 90% confidence interval, 0.44-0.98). Also, 16.7%
      of the infants in the intervention group and 27.3% of the infants in the control
      group developed rhinitis without colds (adjusted relative risk, 0.51; 90%
      confidence interval, 0.35-0.74). The incidence of positive skin test results to 1
      or more inhalant allergens was similar in both groups (4.4% in the intervention
      group and 4.6% in the control group). CONCLUSIONS: Our multifaceted intervention
      program resulted in a modest but significant (P= .04) reduction in the risk of
      possible or probable asthma and rhinitis without apparent colds at the age of 12
      months in high-risk infants. In the absence of a validated definition of asthma
      at the age of 12 months, follow-up studies are needed to determine the
      effectiveness of the intervention program in the primary prevention of asthma in
      high-risk infants.

PMID- 10891017
TI  - How far have state Medicaid agencies advanced in performance measurement for
      children?
AB  - BACKGROUND: While children represent the largest population group enrolled in
      Medicaid managed care, little is known about the pediatric performance measures
      used by state Medicaid agencies. OBJECTIVE: To identify Medicaid managed care
      requirements for using Health Plan Employer Data and Information Set and other
      performance measures for children (defined as those aged 0-21 years in this
      study). DESIGN: A structured telephone survey of pediatric performance measures.
      PARTICIPANTS: Survey respondents were state Medicaid officials responsible for
      managed care quality oversight in 39 states. MAIN OUTCOME MEASURES: Percentage of
      states in 1998 with effectiveness-of-care measures on health promotion and
      disease prevention, early detection and screening, and acute and chronic illness;
      with use measures on preventive care, ambulatory care, pharmacy, inpatient
      hospital care, and mental health and chemical dependency services; and with
      access measures on primary care, low-birth-weight neonates delivered at
      appropriate facilities, and dental care. RESULTS: In 1998, state Medicaid
      agencies placed most of their emphasis on monitoring preventive care for
      children, with immunization rates being the primary focus. Far less attention was
      directed at assessing the treatment of acute illness. Although more than half of
      states monitored the treatment of chronic childhood conditions, they focused
      exclusively on asthma and selected mental health diagnoses. CONCLUSIONS: States
      are still in the initial phases of designing and implementing quality oversight
      systems for Medicaid-insured children. Additional quality reporting requirements
      are clearly needed to assess the treatment of acute and chronic illness among
      children along with more age-specific reporting requirements.

PMID- 10891018
TI  - Intestinal blood loss during cow milk feeding in older infants: quantitative
      measurements.
AB  - OBJECTIVE: To determine the response, in terms of fecal hemoglobin excretion and
      clinical symptoms, of normal 9 1/2-month-old infants to being fed cow milk.
      DESIGN: Longitudinal (before-after) trial in which each infant was fed formula
      for 1 month (baseline) followed by 3 months during which cow milk was fed.
      SETTING: Healthy infants living in Iowa City, Iowa, a town with a population of
      about 60,000. MAIN OUTCOME MEASURES: Hemoglobin concentration in spot stools, 96
      hour quantitative fecal hemoglobin excretion, stool characteristics, feeding
      related behaviors, and iron nutritional status. RESULTS: Fecal hemoglobin
      concentration during formula feeding (baseline) was higher than previously
      observed in younger infants. Nine of 31 infants responded to cow milk feeding
      with increased fecal hemoglobin concentration. Fecal hemoglobin concentration
      (mean +/- SD) of the 9 responders rose from 1,395 +/- 856 microg/g of dry stool
      (baseline) to 2,711 +/- 1,732 microg/g of dry stool (P=.01). The response rate
      (29%) was similar to that in younger infants, but the intensity of the response
      was much less. Quantitative hemoglobin excretion was in general agreement with
      estimates based on spot stool hemoglobin concentrations. Cow milk feeding was not
      associated with recognizable changes in stool characteristics, nor were there
      clinical signs related to fecal blood loss. Iron status was similar, except that
      after 3 months of cow milk feeding responders showed lower (P= .047) ferritin
      concentrations than nonresponders. CONCLUSIONS: Cow milk-induced blood loss is
      present in 9 1/2-month-old infants but is of such low intensity that its clinical
      significance seems questionable. Nevertheless, infants without cow milk-induced
      blood loss were in better iron nutritional status than infants who showed blood
      loss.

PMID- 10891019
TI  - Perceived knowledge and training needs in adolescent pregnancy prevention:
      results from a multidisciplinary survey.
AB  - OBJECTIVES: To examine health care professionals' knowledge and interest in
      training in adolescent pregnancy prevention and whether an association exists
      between perceived knowledge and interest in training. DESIGN: A cross-sectional
      mailed survey. PARTICIPANTS: Random, stratified sample design that identified 800
      psychologists, 800 social workers, 1,000 nurses, and 400 pediatricians from
      national professional membership lists. Response rate to the mailed survey was
      51%. After removing respondents who did not currently work with adolescents,
      1,242 surveys (41%) were available for analyses. MAIN OUTCOME MEASURES:
      Descriptive analyses were conducted on self-report data concerning perceived
      knowledge and interest in training about adolescent pregnancy prevention
      separately for each of the 4 disciplines. Within disciplines, perceived knowledge
      and interest in training were correlated for each of 3 content areas (ie, sex
      education and contraceptive counseling, adolescent pregnancy, and counseling
      after a negative pregnancy test) and for a summary measure of the content areas.
      RESULTS: Less than half of the nursing, pediatrics, psychology, and social work
      professionals reported high perceived knowledge in the 3 content areas.
      Psychologists and social workers reported the lowest perceived knowledge.
      However, with the exception of psychologists, more than two thirds of the other
      respondents reported moderate or high interest in training in the 3 content
      areas. Interest in training was not strongly correlated with perceived knowledge
      within any discipline. CONCLUSIONS: The need to integrate psychosocial components
      into adolescent health care is a core assumption in the field, yet these data
      indicate that psychologists and social workers perceive low levels of knowledge
      and interest in training. These disciplines may benefit from more targeted
      professional training about their role in preventing adolescent pregnancy.

PMID- 10891020
TI  - Barriers pediatricians face when using asthma practice guidelines.
AB  - OBJECTIVE: To describe barriers to the successful use of the 1997 National Heart,
      Lung, and Blood Institute (NHLBI) asthma guidelines. METHODS: We conducted 3
      focus groups to understand barriers to the use of 4 recommendations within the
      NHLBI guidelines (prescription of inhaled corticosteroids, recommendation of
      daily peak flowmeter use, smoking cessation screening and counseling, and
      allergen exposure counseling). PARTICIPANTS: Twenty-one pediatricians and 1 nurse
      practitioner, who each followed an average of 47 patients with asthma,
      participated. Six participants (27%) had a faculty or adjunct appointment at a
      medical school. Nineteen (90%) of the 21 pediatricians were board certified.
      RESULTS: We identified 171 comments about barriers to adherence. Type of
      recommendation and physician year of graduation from medical school were related
      to which barrier was prominent. For corticosteroid prescription, senior
      physicians mentioned lack of agreement, whereas younger physicians described lack
      of confidence in dosing or recognizing contraindications. For peak flow-meter
      use, senior physicians emphasized lack of training. Only senior physicians
      described the inertia of previous practice as a barrier. All groups mentioned
      time limitations. CONCLUSIONS: Efforts to improve adherence to asthma guidelines
      should consider the range of barriers that pediatricians face, such as lack of
      awareness, familiarity, or agreement, and external barriers owing to
      environmental, guideline, or patient factors. In addition, this study documents
      barriers not previously considered, such as lack of self-efficacy, lack of
      outcome expectancy, and inertia of previous practice, that prevent adherence.
      Because type of recommendation and physician demographics are related to which
      barriers are prominent, interventions to improve NHLBI guideline adherence should
      be tailored to these factors.

PMID- 10891021
TI  - Management and outcome of persistent or recurrent fever after initial intravenous
      gamma globulin therapy in acute Kawasaki disease.
AB  - OBJECTIVE: To determine differences in clinical characteristics, laboratory
      findings, and cardiac complications between patients with acute Kawasaki disease
      who received additional treatment for persistent or recurrent fever vs those who
      did not. DESIGN: Nonconcurrent case series; medical record review. SETTING:
      Tertiary care pediatric hospital. PATIENTS: One hundred eighty-five consecutive
      patients diagnosed as having acute Kawasaki disease at The Hospital for Sick
      Children, Toronto, Ontario, from 1995 to 1997. MAIN OUTCOME MEASURE: Prevalence
      of cardiac complications. RESULTS: Twenty-one patients (11%) received additional
      treatment with intravenous gamma globulin (IVGG) with or without intravenous
      methylprednisolone for persistent fever lasting for more than 48 hours or
      recurrent fever after initial treatment with IVGG. Patients who received
      additional treatment did not differ significantly from other patients regarding
      age, sex, race, or diagnostic criteria. Compared with the patients who did not
      receive additional therapy, the patients who received additional treatment had
      shorter median interval from fever onset to initial dose of IVGG (5 vs 6 days;
      P=.006) and longer total days of fever (9 vs 6 days; P<.001). Initial laboratory
      investigations did not differ significantly. On initial echocardiography,
      patients who received additional therapy were significantly more likely to have
      pericardial effusion (33% vs 15%; P=.04), ventricular dysfunction (14% vs 2%; P=
      .002), and coronary artery ectasia (76% vs 43%; P=.004) but not aneurysms (10% vs
      5%; P= .47). At 12 months after diagnosis, there were no significant differences
      between the 2 groups regarding the prevalence of coronary artery ectasia or
      aneurysms. CONCLUSION: Patients receiving additional treatment for persistent or
      recurrent fever have similar demographic and clinical characteristics, greater
      initial cardiac involvement, and similar overall outcomes.

PMID- 10891022
TI  - The World Health Organization oral rehydration solution in US pediatric practice:
      a randomized trial to evaluate parent satisfaction.
AB  - BACKGROUND: The World Health Organization's effective, inexpensive oral
      rehydration solution (WHO-ORS) is used worldwide, but rarely by US practitioners
      because, in part, of concerns about parent satisfaction. OBJECTIVE: To compare
      caretaker satisfaction with the WHO-ORS, a packet-based solution requiring
      preparation, with satisfaction with a commercially prepared oral rehydration
      solution (C-ORS), (Pedialyte; Ross Nutritionals, Columbus, Ohio). DESIGN AND
      METHODS: Randomized controlled trial in an urban pediatric clinic and a suburban
      family medicine clinic. Children aged 3 to 47 months treated as outpatients for
      diarrhea were randomized to receive either WHO-ORS or C-ORS. After 48 hours of
      use, caretakers completed a telephone interview measuring satisfaction with
      aspects of the solution. RESULTS: Of 97 families enrolled, 91 (94%) were
      available for follow-up interviews. The WHO-ORS and C-ORS groups were comparable
      at baseline in all respects, except that slightly more caretakers in the latter
      group had used the C-ORS for the current illness before study enrollment (P=
      .06). Caretakers in the WHO-ORS group had higher overall satisfaction,
      satisfaction with cost, willingness to purchase in the future, and to recommend
      use (P<.001 for all). Differences remained significant after controlling for
      prior use of the C-ORS. There was no difference in satisfaction with ease of
      administration (P=.90), appearance (P=.20), and effectiveness (P=.80). No adverse
      effects attributable to either study solution occurred. CONCLUSIONS: Caretakers
      who prepared and used the WHO-ORS were more satisfied with their solution than a
      comparable group who administered C-ORS. Fear of parental dissatisfaction need
      not be a barrier to use of the WHO-ORS in the United States.

PMID- 10891023
TI  - Relationship between disease and psychological adaptation in children in the
      Childhood Asthma Management Program and their families. CAMP Research Group.
AB  - OBJECTIVE: To test the hypotheses that the burden of childhood asthma compromises
      psychological adaptation and that the degree of compromise increases with disease
      severity. DESIGN: The Childhood Asthma Management Program (CAMP) is a multicenter
      randomized clinical trial initiated and funded by the National Heart, Lung, and
      Blood Institute. SETTING: Study sites were located in Albuquerque, NM, Baltimore,
      Md, Boston, Mass, Denver, Colo, St Louis, Mo, San Diego, Calif, Seattle, Wash,
      and Toronto, Ontario. PARTICIPANTS: A total of 1,041 children aged 5 to 12 years
      were randomized to the trial after confirming their mild to moderate asthma. MAIN
      OUTCOME MEASURES: Psychological questionnaires administered at baseline to
      parents and participants assessed anxiety, depression, behavioral competence,
      social support, and family functioning. RESULTS: Psychological difficulty was not
      increased in this group of asthmatic children and their families. Psychological
      adaptation in the children was associated with the psychological adaptation of
      the family but not with disease-related variables. Scores from the Impact on
      Family Scale, a measure of family quality of life related to the child's illness,
      were associated more strongly with the overall psychological characteristics of
      the family and child and very little with disease characteristics or severity.
      CONCLUSIONS: Mild to moderate asthma has imposed modest effects on the daily life
      but not the psychological health of this group of children. Variation in the
      psychological characteristics of these children was, as is the case for most
      children, traceable to the overall psychological adaptation of their families.

PMID- 10891024
TI  - The magnitude and challenge of false-positive newborn screening test results.
AB  - OBJECTIVES: This study examined for the first time to our knowledge the national
      data available from newborn screening programs in the United States and
      determined the salient characteristics of various screening tests for 3
      hereditary metabolic disorders and 2 congenital endocrinopathies with emphasis on
      positive predictive values (PPVs) to delineate the magnitude of false-positive
      results. METHODS: Reports published by the Council of Regional Networks for
      Genetic Services for 1990 through 1994 were examined carefully, paying particular
      attention to phenylketonuria, galactosemia, biotinidase deficiency, congenital
      hypothyroidism, and congenital adrenal hyperplasia (CAH). Because of recent
      improvements in data collecting, reporting, and tabulating, we used data from
      1993 and 1994 to determine the apparent sensitivity, specificity, relative
      incidence rates, and PPVs for the 5 disorders. For biotinidase deficiency and
      CAH, we also calculated relative incidence rates and PPVs for 1991 and 1992.
      RESULTS: Our analyses revealed the following best estimates for the relative
      incidence rates of 5 disorders: phenylketonuria, 1:14,000; galactosemia,
      1:59,000; biotinidase deficiency, 1:80,000; congenital hypothyroidism, 1:3,300;
      and CAH, 1:20,000. An apparent sensitivity of 100% has been reported by the
      various states for most of the disorders, and specificity levels are all above
      99%. The PPVs, however, range from 0.5% to 6.0%. Consequently, on average, there
      are more than 50 false-positive results for every true-positive result identified
      through newborn screening in the United States. CONCLUSIONS: The magnitude of
      false-positive results generated in newborn screening programs, particularly for
      congenital endocrinopathies, presents a great challenge for future improvement of
      this important public health program. Attention must be given to improved
      laboratory tests, use of more specific markers, and better risk communication for
      families of patients with false-positive test results.

PMID- 10891025
TI  - Behavioral interventions reduce infant distress at immunization.
AB  - OBJECTIVE: To assess the effectiveness of simple behavioral interventions at
      immunization on behavioral and biochemical indicators of distress in infants and
      parents in a primary care setting. DESIGN: Subjects were enrolled sequentially to
      control (standard care) and intervention groups. Intervention parents (n=57) were
      provided information about techniques to help their infants at immunization.
      Standard care parents (n=45) did not receive this information. Immunizations were
      videotaped and coded for infant and parent behaviors. Using a visual analog
      scale, parents rated their infant's and their own comfort at study enrollment,
      immediately after immunization, and at check-out. Saliva samples collected from
      infants and parents at study enrollment and at 15, 30, and 60 minutes after
      immunization were assayed for cortisol concentration by standard
      radioimmunoassay. Data were analyzed using chi2, analysis of variance, and
      general linear modeling. Patterns of salivary cortisol change after immunization
      were analyzed using hierarchical linear modeling. SETTING: A single, urban
      pediatric practice during 2 summers (1997 and 1998). SUBJECTS: Infants 2 to 24
      months of age (n= 102) and their parents. MAIN OUTCOME MEASURES: Duration of
      infant distress (in seconds); parent use of behavioral intervention; infant and
      parent salivary cortisol concentrations (in nanomoles per liter). RESULTS:
      Intervention parents were more likely to use a behavioral technique with their
      infants before immunization (P<.05). Total infant distress was shorter for
      intervention infants at immunization (P<.01), and these infants were rated as
      more comfortable by their parents (P<.001) immediately after immunization.
      Salivary cortisol levels were lower for intervention infants at 15, 30, and 60
      minutes after immunization (P<.05). CONCLUSION: Simple behavioral interventions
      before immunization are associated with reductions in behavioral and biochemical
      indicators of infant distress.

PMID- 10891026
TI  - Neurodevelopment and predictors of outcomes of children with birth weights of
      less than 1000 g: 1992-1995.
AB  - OBJECTIVE: To examine the neurosensory and cognitive status of extremely low
      birth-weight (ELBW; < 1,000 g) children born from January 1, 1992, through
      December 31, 1995, and to identify the significant predictors of outcome. DESIGN:
      An inception cohort of ELBW infants admitted to the neonatal intensive care unit
      (NICU) and observed to 20 months' corrected age. SETTING: A tertiary level urban
      NICU and follow-up clinic at a university hospital. POPULATION: Of 333 ELBW
      infants without major congenital malformations admitted to the NICU, 241 (72%)
      survived to 20 months' corrected age. We studied 221 children (92%) at a mean of
      20 months' corrected age. The mean birth weight was 813 g; mean gestational age,
      26.4 weeks. MAIN OUTCOME MEASURES: Assessments of cognitive and neurosensory
      development. RESULTS: Major neurosensory abnormality was present in 54 children
      (24%), including 33 (15%) with cerebral palsy, 20 (9%) with deafness, and 2 (1%)
      with blindness. The mean (+/- SD) Bayley-Mental Developmental Index (MDI) score
      was 74.7 +/- 17. Ninety-two children (42%) had a subnormal MDI score (<70).
      Neurodevelopmental impairment (neurosensory abnormality and/or MDI score <70) was
      present in 105 children (48%). Multiple stepwise logistic regression analysis
      that considered sex, social risk, birth weight, and neonatal risk factors
      revealed significant predictors of a subnormal MDI score to be male sex (odds
      ratio [OR], 2.73; 95% confidence interval [CI], 1.52-4.92), social risk (OR,
      1.48; 95% CI, 1.09-2.00), and chronic lung disease (OR, 2.18; 95% CI, 1.20-3.94).
      Predictors of neurologic abnormality were a severely abnormal finding on cerebral
      ultrasound (OR, 8.09; 95% CI, 3.69-17.71) and chronic lung disease (OR, 2.46; 95%
      CI, 1.12-5.40); predictors of deafness were male sex (OR, 2.79; 95% CI, 1.02
      7.62), sepsis (OR, 3.15; 95% CI, 1.05-9.48), and jaundice (maximal bilirubin
      level, >171 micromol/L [>10 mg/dL]) (OR, 4.80; 95% CI, 1.46-15.73). CONCLUSION:
      There is an urgent need for research into the etiology and prevention of neonatal
      morbidity.

PMID- 10891027
TI  - Scurvy presenting as painful gait with bruising in a young boy.
AB  - A case of scurvy occurred in an apparently well-nourished 5-year-old boy with
      normal growth parameters. Only after the diagnosis of scurvy was raised on
      clinical grounds did we discover the peculiar dietary habits that were
      responsible for his deficiency of ascorbic acid. His case is a reminder to the
      clinician that nutritionally based disease may occur in any socioeconomic setting
      and that nutritional screening remains an important part of every child's general
      health care.

PMID- 10891028
TI  - The objective structured clinical examination: a step in the direction of
      competency-based evaluation.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education is embarking
      on the major task of a paradigm shift in graduate education in the direction of
      competency-based medical education and evaluation of outcomes. The Objective
      Structured Clinical Examination (OSCE), a measure of clinical competence that
      focuses on outcomes via observable behaviors, is gaining national recognition.
      OBJECTIVE: To review the pediatric literature relevant to the OSCE. METHOD: A
      MEDLINE search from the date of the original report of the OSCE (1975) to the
      present was performed. All English-language studies regarding the use of the OSCE
      in pediatric education published in the United States and Great Britain were
      reviewed. MAIN OUTCOME MEASURES: Reliability and validity of the OSCE were
      examined. Use of standardized pediatric patients was discussed. RESULTS: A
      greater number of stations and similarity between tasks at different stations
      increased the reliability of the OSCE. A greater number of stations increased
      sampling of material and content validity. Correlation between the OSCE and
      precertification examinations ranged between 0.59 and 0.71, with P< or =.01.
      Correlation between the OSCE and monthly clinical evaluations was much lower
      (0.39-0.57), but still statistically significant at P< or =.05. Gaps between
      expected and actual performance were documented. Overall, the experience of being
      a standardized patient was viewed as positive by children and their parents.
      CONCLUSIONS: With appropriate attention to design, acceptable reliability and
      validity can be achieved for the OSCE. Significant correlations between the OSCE
      and precertification examinations as well as monthly clinical evaluations were
      found, the former being stronger than the latter. We conclude that the
      combination of the OSCE, standardized board examinations, and direct observation
      in the clinical setting has the potential to become the "gold standard" for
      measuring physician competence.

PMID- 10891029
TI  - Radiological case of the month. Hepatic hemangiomatosis.

PMID- 10891030
TI  - Picture of the month. Autoimmune polyglandular syndrome type 1.

PMID- 10891031
TI  - Pathological case of the month. Campomelic dysplasia.

PMID- 10891032
TI  - No radiograph in the management of pediatric torus fractures.

PMID- 10891033
TI  - The Pediatric Forum: No Radiograph in the Management of Pediatric Torus
      Fractures.

PMID- 10891034
TI  - Schizophrenia as a disorder of developmentally reduced synaptic connectivity.
AB  - Recent postmortem and neuroimaging studies of schizophrenia delineate changes in
      brain structure and volume that appear to arise from a reduction of neuritic
      processes (such as dendrites and synapses) rather than loss of neuronal or glial
      cell bodies. To account for these findings, we propose a pathophysiological model
      of reduced synaptic connectivity arising from disturbances of brain development
      active during perinatal and adolescent periods. We review a computer simulation
      of the elimination of the synaptic connections that models normal cognitive
      development and psychotic symptom formation. We describe the model's key
      parameters and discuss how they can account for important aspects of
      schizophrenia, including its unique symptoms, short- and long-term course,
      typical age of onset, neurodevelopmental deficits, limited neurodegenerative
      progression, sex differences, and more. We discuss some of the model's
      predictions and questions raised for basic research, early detection, and
      preventive intervention.

PMID- 10891035
TI  - A double-blind placebo-controlled study of lithium in hospitalized aggressive
      children and adolescents with conduct disorder.
AB  - BACKGROUND: A subgroup of children and adolescents with conduct disorder are
      characterized by severe and persistent aggression. Although there is no agreed on
      treatment for such aggression, lithium carbonate has shown promise in some
      studies involving children. Our study was designed to critically assess the
      efficacy of lithium in the treatment of aggression in children and adolescents
      using a measure specific for aggression. METHODS: Subjects were inpatients with
      conduct disorder hospitalized because of severe and chronic aggression. A
      parallel-groups design was used in this double-blind, placebo-controlled trial
      with randomization to lithium or placebo. Only those who met the aggression
      criterion during the 2-week placebo-baseline period were randomized to 4 weeks of
      treatment. Outcome measures included Clinical Global Impressions, the Global
      Clinical Judgements (Consensus) Scale, and the Overt Aggression Scale. RESULTS:
      Eighty-six inpatients enrolled in the study; 40 (33 male and 7 female; median
      age, 12.5 years) entered and completed the treatment phase. Lithium was
      statistically and clinically superior to placebo. Sixteen of 20 subjects in the
      lithium group were responders on the Consensus ratings vs 6 of 20 in the placebo
      group (P=.004). Ratings on the Overt Aggression Scale decreased significantly for
      the lithium group vs the placebo group (P=.04). More than half of the subjects in
      the lithium group experienced nausea, vomiting, and urinary frequency.
      CONCLUSIONS: Lithium is a safe and effective short-term treatment for aggression
      in inpatients with conduct disorder, although its use is associated with adverse
      effects.

PMID- 10891036
TI  - The natural course of bulimia nervosa and binge eating disorder in young women.
AB  - BACKGROUND: Little is known about the relative course and outcome of bulimia
      nervosa and binge eating disorder. METHODS: Two community-based cohorts were
      studied prospectively over a 5-year year period. One comprised 102 participants
      with bulimia nervosa and the other 48 participants with binge eating disorder
      (21% [9/42] of whom had comorbid obesity). All participants were female and aged
      between 16 and 35 years at recruitment. The assessments were at 15-month
      intervals and addressed eating disorder features, general psychiatric symptoms,
      and social functioning. RESULTS: Both cohorts showed marked initial improvement
      followed by gradual improvement thereafter. Between half and two thirds of the
      bulimia nervosa cohort had some form of eating disorder of clinical severity at
      each assessment point, although only a minority continued to meet diagnostic
      criteria for bulimia nervosa. Each year about a third remitted and a third
      relapsed. The outcome of the binge eating disorder cohort was better, with the
      proportion with any form of clinical eating disorder declining to 18% (7 of 40)
      by the 5-year follow-up. The relapse rate was low among this cohort. There was
      little movement of participants across the 2 diagnostic categories and few sought
      treatment. Both groups gained weight, with 39% of the binge eating disorder
      cohort (14 of 36) meeting criteria for obesity at 5-year follow-up. CONCLUSIONS:
      These findings suggest that, among young women in the community, bulimia nervosa
      and binge eating disorder have a different course and outcome. Whereas the
      prognosis of those with bulimia nervosa was relatively poor, the great majority
      of those with binge eating disorder recovered.

PMID- 10891037
TI  - Common genetic vulnerability for pathological gambling and alcohol dependence in
      men.
AB  - BACKGROUND: In comparison with alcohol dependence (AD), relatively little is
      known about the causes of pathological gambling (PG). Given the high rate of
      comorbidity between PG and AD, knowledge about the causes of AD may be applied to
      understanding those of PG. METHODS: Subjects were adult male twin pairs from the
      Vietnam Era Twin Registry. Lifetime histories of PG and AD were assessed by
      structured psychiatric telephone interview. The validity of a continuum of PG
      liability was tested to determine whether the causes of subclinical PG, or
      problem gambling, are quantitatively or qualitatively distinct from those of DSM
      III-R PG disorder. Genetic model-fitting methods were used to quantify the extent
      to which the genetic and environmental risk for PG could be explained by the risk
      for AD. RESULTS: Tests of the continuity model of PG were all consistent with the
      hypothesis that subclinical PG and DSM-III-R PG disorder have many, perhaps all,
      of the same risk factors and thus differ quantitatively rather than
      qualitatively. Depending on the PG definition, between 12% and 20% of the genetic
      variation and between 3% and 8% of the nonshared environmental variation in the
      risk for PG were accounted for by the risk for AD. CONCLUSIONS: Subclinical PG,
      or problem gambling, may be a milder form of PG, rather than an etiologically
      distinct syndrome. Risk for AD accounts for a significant but modest proportion
      of the genetic and environmental risk for subclinical PG and DSM-III-R PG
      disorder.

PMID- 10891038
TI  - Brief screening for family psychiatric history: the family history screen.
AB  - BACKGROUND: Brief screens to collect lifetime family psychiatric history are
      useful in clinical practice and for identifying potential families for genetic
      studies. METHODS: The Family History Screen (FHS) collects information on 15
      psychiatric disorders and suicidal behavior in informants and their first-degree
      relatives. Since each question is posed only once about all family members as a
      group, the administrative time is 5 to 20 minutes, depending on family size and
      illness. Data on the validity against best-estimate (BE) diagnosis based on
      independent and blind direct interviews on 289 probands and 305 relatives and
      test-retest reliability across 15 months in 417 subjects are presented. RESULTS:
      Agreement between FHS and BE diagnosis for proband and relative self-report had
      median sensitivity (SEN) of 67.6 and 71.1 respectively; median specificity (SPC)
      was 87.6 and 89.4, respectively. Marked decrease in SEN occurred when a single
      informant (the proband) reported on a relative (median, 37.5); however, median
      SPC was 95.8. Use of more than 1 informant substantially improved SEN (median,
      68.2), with a modest reduction in SPC (median, 86.8). Test-retest reliability
      across 15 months resulted in a median kappa of 0.56. CONCLUSIONS: The FHS is a
      promising brief screen for collecting lifetime psychiatric history on an
      informant and/or first-degree relatives. Its validity is best demonstrated for
      major depression, anxiety disorders, substance dependence (alcohol and drug
      dependence), and suicide attempts. It is not a substitute for more lengthy family
      history if more detail on diagnosis is required.

PMID- 10891039
TI  - Increased levels of transcription factors Elk-1, cyclic adenosine monophosphate
      response element-binding protein, and activating transcription factor 2 in the
      cerebellar vermis of schizophrenic patients.
AB  - BACKGROUND: We investigated the levels of transcription factors associated with
      activation of the mitogen-activated protein (MAP) kinase pathway in
      schizophrenics using postmortem brain samples. These studies were done to
      determine whether our previous findings of abnormal levels of the MAP kinases in
      the cerebellar vermis were linked to additional downstream targets of this signal
      transduction pathway. METHOD: We measured the protein levels of 3 transcription
      factors in nuclear fractions of postmortem samples from cerebellar vermis of 10
      patients with schizophrenia and 13 control subjects: Elk-1, cyclic adenosine
      monophosphate (cAMP) response element binding protein (CREB), and activating
      transcription factor 2 (ATF-2). Studies in rats examined the postmortem stability
      and effect of haloperidol and risperidone on levels of Elk-1, cAMP, and ATF-2
      proteins. RESULTS: We found a significant increase in the protein levels of Elk-1
      (mean+SD, 4489+/-659 vs 2915+/-583 arbitrary densitometric units [P<.001]), CREB
      (mean +/- SD, 2149 1061 vs 904+/-711 arbitrary densitometric units [P=.003]) and
      ATF-2 (mean+/-SD, 1421 854 vs 512+/-394 arbitrary densitometric units [P=.003])
      in the cerebellar vermis of schizophrenic subjects. Complementary studies in rats
      indicate that these findings can not be attributed to subacute treatment with
      antipsychotic medications. CONCLUSION: Taken together with the alterations of MAP
      kinases previously reported, and the findings of elevations of downstream
      transcription targets, we suggest that the MAP kinase signal transduction pathway
      contributes to the cerebellar abnormalities in schizophrenia.

PMID- 10891041
TI  - Severe mental illness and substance use disorders among former Supplemental
      Security Income beneficiaries for drug addiction and alcoholism.
AB  - BACKGROUND: Recently enacted federal legislation targeted at curbing perceived
      abuses of cash benefits for former Supplemental Security Income beneficiaries for
      drug addiction and/or alcoholism (DA&A) may be creating a residual population
      that is too seriously impaired to work owing to psychiatric and substance use
      disorders. METHOD: Data in this report were derived from 1-year follow-up
      interviews of 204 randomly selected DA&A beneficiaries in Chicago who were
      initially interviewed between January 1997 and March 1997, immediately following
      their termination in the Supplemental Security Income DA&A program. Information
      on subjects' work and benefits status were collected along with DSM-III-R
      psychiatric and substance use disorder diagnostic information. Urine specimens
      were also collected and tested for recent use of marijuana, cocaine, opiates,
      phencyclidine, amphetamines, and methadone. RESULTS: Twenty-six percent had a
      past-year severe mental illness while 34% met the DSM-III-R criteria for drug
      dependence. Illegal drug use was also prevalent with about 50% of the sample
      testing positive for marijuana, cocaine, or opiates. Compared with those working
      and earning at least $500 a month, unemployed or underemployed subjects who had
      lost all federal benefits had a much greater likelihood of being dependent on
      drugs (odds ratio, 5.0; P<.005; 95% confidence interval, 1.6-15.7) and of having
      2 or more comorbid psychiatric disorders (odds ratio, 6.9; P<.005; 95% confidence
      interval, 1.9-24.7). CONCLUSIONS: Those who have lost DA&A disability benefits
      and who continue to be unemployed or underemployed have elevated rates of drug
      dependence and psychiatric comorbidities; consequently, helping these cases make
      the transition from government assistance to sustained employment is increasingly
      difficult.

PMID- 10891040
TI  - Planum temporale and Heschl gyrus volume reduction in schizophrenia: a magnetic
      resonance imaging study of first-episode patients.
AB  - BACKGROUND: Magnetic resonance imaging studies in schizophrenia have revealed
      abnormalities in temporal lobe structures, including the superior temporal gyrus.
      More specifically, abnormalities have been reported in the posterior superior
      temporal gyrus, which includes the Heschl gyrus and planum temporale, the latter
      being an important substrate for language. However, the specificity of the Heschl
      gyrus and planum temporale structural abnormalities to schizophrenia vs affective
      psychosis, and the possible confounding roles of chronic morbidity and
      neuroleptic treatment, remain unclear. METHODS: Magnetic resonance images were
      acquired using a 1.5-T magnet from 20 first-episode (at first hospitalization)
      patients with schizophrenia (mean age, 27.3 years), 24 first-episode patients
      with manic psychosis (mean age, 23.6 years), and 22 controls (mean age, 24.5
      years). There was no significant difference in age for the 3 groups. All brain
      images were uniformly aligned and then reformatted and resampled to yield
      isotropic voxels. RESULTS: Gray matter volume of the left planum temporale
      differed among the 3 groups. The patients with schizophrenia had significantly
      smaller left planum temporale volume than controls (20.0%) and patients with
      mania (20.0%). Heschl gyrus gray matter volume (left and right) was also reduced
      in patients with schizophrenia compared with controls (13.1%) and patients with
      bipolar mania (16.8%). CONCLUSIONS: Compared with controls and patients with
      bipolar manic psychosis, patients with first-episode schizophrenia showed left
      planum temporale gray matter volume reduction and bilateral Heschl gyrus gray
      matter volume reduction. These findings are similar to those reported in patients
      with chronic schizophrenia and suggest that such abnormalities are present at
      first episode and are specific to schizophrenia.

PMID- 10891042
TI  - Use of practitioner-based complementary therapies by persons reporting mental
      conditions in the United States.
AB  - BACKGROUND: To our knowledge, this study provides the first national estimates
      for use of practitioner-based complementary treatments by US residents reporting
      mental conditions. METHODS: A total of 16038 respondents to the 1996 Medical
      Expenditure Panel Survey were asked about visits for 12 complementary medical
      services (eg, chiropractic services and herbal remedies). Bivariate and multiple
      regression models examined use of these therapies in individuals reporting a
      mental condition (n= 1803), fair or poor mental health status (n=992), and 1 of 4
      chronic medical conditions (n = 3262) and in the remainder of the sample (n= 10
      793). RESULTS: A total of 9.8% of those reporting a mental condition made a
      complementary visit, and about half of these (4.5%) made a visit to treat the
      mental condition. Persons reporting transient stress or adjustment disorders were
      most likely (odds ratio, 9.1%; 95% confidence interval, 5.5%-12.7%), and those
      with psychotic (odds ratio, 1.5%; 95% confidence interval, 0.0%-4.2%) and
      affective (odds ratio, 2.6%; 95% confidence interval, 1.5%-3.8%) conditions least
      likely, to use complementary therapies to treat their mental condition. In
      multivariate models controlling for medical comorbidity, fair or poor mental
      health status, and demographic factors, report of a mental condition predicted a
      1.27-fold increase in the odds of a complementary visit (95% confidence interval,
      1.04-1.54). CONCLUSIONS: Self-reported mental conditions were associated with
      increased use of complementary treatments, although use of these treatments was
      concentrated in respondents with transient distress rather than chronic and
      serious conditions. More research using structured diagnostic interviews is
      needed to examine the prevalence, patterns, and clinical implications of use of
      these treatments by individuals with mental conditions in "real world" community
      settings.

PMID- 10891044
TI  - The effects of olive oil on omega3 fatty acids and mood disorders.

PMID- 10891045
TI  - Hypomania associated with omega3 fatty acids.

PMID- 10891047
TI  - Are omega3 fatty acids beneficial in depression but not mania?

PMID- 10891048
TI  - Catalytic Asymmetric Synthesis Special Issue.

PMID- 10891049
TI  - Catalytic asymmetric synthesis.

PMID- 10891050
TI  - Chiral bis(oxazoline) copper(II) complexes: versatile catalysts for
      enantioselective cycloaddition, Aldol, Michael, and carbonyl ene reactions.
AB  - A bis(oxazoline) (box) copper(II) complex and its hydrated counterpart (1 and 2)
      function as enantioselective Lewis acid catalysts for carbocyclic and hetero
      Diels-Alder, aldol, Michael, ene, and amination reactions with substrates capable
      of chelation through six- and five-membered rings. X-ray crystallography of the
      chiral complexes reveals a propensity for the formation of distorted square
      planar or square pyramidal geometries. The sense of asymmetric induction is
      identical for all the processes catalyzed by [Cu((S,S)-t-Bu-box)](X)(2) complexes
      1 and 2 (X = OTf and SbF) resulting from the intervention of a distorted square
      planar catalyst-substrate binary complex. These catalyzed processes exhibit
      excellent temperature-selectivity profiles. Reactions catalyzed by [Cu(S,S-Ph
      pybox)](SbF(6))(2) and their derived chelation complexes are also discussed.

PMID- 10891051
TI  - Phosphinooxazolines--a new class of versatile, modular P,N-ligands for asymmetric
      catalysis.
AB  - Chiral phosphinooxazolines (PHOX ligands), which coordinate to a metal center
      with a N- and a P-atom, allow effective enantiocontrol in a variety of metal
      catalyzed reactions. They are readily synthesized, and because of their modular
      structure, the steric and electronic properties can be tailored for a specific
      application by variation of the oxazoline ring, the backbone, and the phosphine
      moiety.

PMID- 10891052
TI  - Phosphoramidites: marvellous ligands in catalytic asymmetric conjugate addition.
AB  - The development of an efficient catalytic system for enantioselective carbon
      carbon bond formation by 1,4-addition of organometallic reagents (organolithium,
      Grignard, and organozinc reagents) to enones is a major challenge in organic
      synthesis. This Account presents the breakthrough realized in this field using
      chiral phosphoramidite ligands for copper-catalyzed dialkylzinc additions.
      Applications in catalytic routes to cycloalkanones as well as tandem and
      annulation procedures with excellent enantioselectivities are discussed.

PMID- 10891053
TI  - Chiral monodentate phosphine ligand MOP for transition-metal-catalyzed asymmetric
      reactions.
AB  - Chiral monophosphines, whose chirality is due to biaryl axial chirality, have
      been prepared from enantiomerically pure 2, 2'-dihydroxy-1,1'-binaphthyl and
      demonstrated to be highly efficient chiral ligands for transition-metal-catalyzed
      organic transformations, especially for reactions where chelating bisphosphine
      ligands cannot be used. The high efficiency is observed in palladium-catalyzed
      asymmetric hydrosilylation of a wide variety of olefins such as alkyl-substituted
      terminal olefins and in asymmetric reactions via pi-allylpalladium intermediates
      represented by asymmetric reduction of allylic esters with formic acid.

PMID- 10891054
TI  - Modular phospholane ligands in asymmetric catalysis.
AB  - This Account outlines the preparation and application of a class of phosphine
      ligands based upon the trans-2,5-disubstituted phospholane moiety. The modular
      nature of these ligands has allowed facile variation of both phospholane
      substituent and backbone structure, thus providing access to a series of ligands.
      Bidentate bis(phospholane) ligands have been found to be very useful in
      asymmetric catalytic hydrogenation reactions. In particular, we highlight the
      versatility of highly efficient bis(phospholane)rhodium catalysts that allow
      enantioselective hydrogenation to produce a diverse range of compounds containing
      C-N, C-O, and C-C stereogenic centers.

PMID- 10891055
TI  - The discovery of novel reactivity in the development of C-C bond-forming
      reactions: in situ generation of zinc acetylides with Zn(II)/R(3)N.
AB  - There have been great strides in expanding the scope, application, and
      versatility of known reaction types (i.e., Mukaiyama aldol). It is interesting to
      speculate that limitations in the number of such known basic reaction types
      constitute the greatest barrier in the development of practical processes. The
      catalytic generation of transition-metal metalloenolates and alkynilides under
      conditions compatible with electrophilic reaction partners provides fresh avenues
      for the development of new efficient asymmetric processes leading to C-C bond
      formation.

PMID- 10891056
TI  - Enantioselective automultiplication of chiral molecules by asymmetric
      autocatalysis.
AB  - Asymmetric autocatalysis is a process of automultiplication of a chiral compound
      in which chiral product acts as a chiral catalyst for its own production. The
      discovery and the development of asymmetric autocatalysis of pyrimidyl-, quinolyl
      , and pyridylalkanols are described in the enantioselective additions of
      diisopropylzinc to the corresponding nitrogen-containing aldehydes.
      (Alkynylpyrimidyl)alkanols automultiply with a yield of over 99% and over 99.5%
      ee. Asymmetric autocatalysts with extremely low ee's automultiply with
      significant amplification of ee's without the need for any other chiral
      auxiliaries. Small enantiomeric imbalances of chiral molecules induced by
      physical factors can be amplified by the present asymmetric autocatalysis.

PMID- 10891057
TI  - Enantiomer-selective activation of racemic catalysts.
AB  - Asymmetric catalysts can be evolved into highly activated catalysts by
      association with chiral activators. This asymmetric activation process is
      particularly useful in racemic catalysis through selective activation of one
      enantiomer of the racemic catalysts. Recently, a strategy whereby a racemic
      catalyst is selectively deactivated by a chiral additive has been reported to
      yield nonracemic products. However, we have reported a strategy that is an
      alternative to asymmetric catalysts but is conceptually opposite, in which a
      chiral activator selectively activates rather than deactivates one enantiomer of
      a racemic chiral catalyst. The advantage of this activation strategy over the
      deactivation counterpart is that the activated catalyst can produce a greater
      enantiomeric excess (x(act)% ee) in the products than the ee attained by the
      enantiomerically pure catalyst on its own. Therefore, 'asymmetric activation'
      could provide a general and powerful strategy for the use of not only
      atropisomeric and, hence, racemic ligands but also chirally flexible and 'pro
      atropisomeric' ligands without enantiomeric resolution!

PMID- 10891058
TI  - Kinetic aspects of nonlinear effects in asymmetric catalysis.
AB  - Probing catalyst systems for a nonlinear relationship between product
      enantioselectivity and catalyst enantiopurity is now commonly being used as a
      mechanistic tool. We show that in some cases striking consequences for reaction
      rate can ensue for reactions carried out using non-enantiopure catalysts. We also
      demonstrate how consideration of the kinetic behavior may serve to enhance the
      use of nonlinear effects as a diagnostic tool for identifying active catalytic
      species and for providing mechanistic insight. Kinetic information may also help
      in the development of efficient synthetic strategies using non-enantiopure
      systems.

PMID- 10891059
TI  - Enantioselective nucleophilic catalysis with "Planar-Chiral" heterocycles.
AB  - Although Lewis bases (e.g., tertiary phosphines, tertiary amines, and pyridines)
      serve as nucleophilic catalysts for a wide array of reactions, there have been
      relatively few reports of enantioselective nucleophilic catalysts. In this
      Account, we describe the design and synthesis of a new family of chiral
      nucleophilic catalysts, specifically, planar-chiral heterocycles. These complexes
      provide good levels of enantiomeric excess in the addition of alcohols to
      ketenes, the rearrangement of O-acylated azlactones, and the kinetic resolution
      of secondary alcohols.

PMID- 10891060
TI  - Asymmetric catalysis of epoxide ring-opening reactions.
AB  - The discovery of the metal salen-catalyzed asymmetric ring-opening (ARO) of
      epoxides is chronicled. A screening approach was adopted for the identification
      of catalysts for the addition of TMSN(3) to meso-epoxides, and the chiral
      (salen)CrN(3) complex was identified as optimal. Kinetic and structural studies
      served to elucidate the mechanism of catalysis, which involves cooperative
      activation of both epoxide and azide by two different metal centers. Covalently
      linked bimetallic complexes were constructed on the basis of this insight, and
      shown to catalyze the ARO with identical enantioselectivity but 1-2 orders of
      magnitude greater reactivity than the monomeric analogues. Extraordinarily high
      selectivity is observed in the kinetic resolution of terminal epoxides using the
      (salen)CrN(3)/TMSN(3) system. A search for a practical method for the kinetic
      resolution reaction led to the discovery of highly enantiomer-selective
      hydrolytic ring-opening using the corresponding (salen)Co(III) catalyst. This
      system displays extraordinary substrate generality, and allows practical access
      to enantiopure terminal epoxides on both laboratory and industrial scales.

PMID- 10891061
TI  - Asymmetric catalysis of aldol reactions with chiral lewis bases.
AB  - In an extension of studies both on the stereochemical course of the aldol
      addition and on Lewis-base-catalyzed allylation reactions, we have invented a new
      Lewis-base-catalyzed asymmetric aldol addition. This Account outlines the
      conceptual development, the identification of design criteria, and the underlying
      principles for such a process. The reduction of these elements to practice in the
      demonstration of enantioselective aldol additions of trichlorosilyl enolates
      catalyzed by chiral phosphoramides is also presented. From a combination of
      stereochemical, kinetic, and structural studies, an intruiging mechanistic
      hypothesis is forwarded that explains the origin of catalysis and
      diastereoselectivity.

PMID- 10891062
TI  - Regulation of cytosolic phospholipase A(2) in a new perspective: recruitment of
      active monomers from an inactive clustered pool.
AB  - cPLA(2) plays a key role in many signal transduction cascades by hydrolyzing
      arachidonic acid from membrane phospholipids. Tight control of cPLA(2) activity
      by a number of regulatory mechanisms is essential to its cellular function. We
      recently described the localization of cPLA(2) in clusters in fibroblasts and now
      propose that these clusters reflect a localized inactive pool from which active
      monomers can be recruited to keep cPLA(2) activity under control on the
      subcellular level. Using an electron microscopic in vitro approach, we show that
      cPLA(2) monomers, but not the clusters, bind to membranes in a Ca(2+)-dependent
      manner. This binding is accompanied by hydrolytic activity. The present data
      combined with our previous observation of a relative abundance of clusters over
      monomers in fixed fibroblasts [Bunt, G., de Wit, J., van den Bosch, H., Verkleij,
      A., and Boonstra, J. (1997) J. Cell Sci. 110, 2449-2459] gives rise to a concept
      of cPLA(2) regulation in which small amounts of active monomers are recruited to
      fulfill their function upon stimulation. This is in contrast to processes
      described for inflammatory cells, where a substantial part of the cytoplasmically
      localized cPLA(2) translocates to the perinuclear region upon stimulation to
      become active. Small-scale regulation of cPLA(2) by the proposed cluster-monomer
      cycle allows local and strictly confined control of cPLA(2) activity, apparently
      necessary for its cellular role in fibroblasts.

PMID- 10891063
TI  - Structural constraints imposed by a non-native disulfide cause reversible changes
      in rhodopsin photointermediate kinetics.
AB  - Suspensions of bovine rhodopsin in 2% lauryl maltoside detergent were treated
      with Cu(phen)(3)(2+) to form a disulfide bridge between cysteines 140 and 222
      which occur naturally in the bovine rhodopsin sequence. Absorption difference
      spectra were collected after excitation with a pulse of 477 nm light on the time
      scale from 1 micros to 690 ms, and the results were analyzed using global
      exponential fitting. Only two exponentials could be fit to data from the
      Cu(phen)(3)(2+)-treated rhodopsin, while three exponentials were needed to fit
      data either from untreated rhodopsin or from Cu(phen)(3)(2+)-oxidized rhodopsin
      after further dithiothreitol reduction. Dithiothreitol treatment of rhodopsin
      which had not been previously oxidized with Cu(phen)(3)(2+) had no effect on the
      observed kinetics. Since the 140-222 disulfide has previously been shown to block
      transducin activation, its effects on rhodopsin activation are of considerable
      interest. Cu(phen)(3)(2+) treatment favors formation of the meta I(380)
      intermediate relative to meta I(480) and slows formation of meta II from meta
      I(380). This suggests that the protein change involved in meta I(380) formation
      is similar to the structural constraint introduced by the 140-222 disulfide.
      These results show that formation of disulfides in rhodopsin has potential as a
      tool for discriminating between the three isochromic, 380 nm absorbing
      intermediates involved in rhodopsin activation and for gaining insight into how
      their structures differ.

PMID- 10891064
TI  - IscU as a scaffold for iron-sulfur cluster biosynthesis: sequential assembly of
      [2Fe-2S] and [4Fe-4S] clusters in IscU.
AB  - Iron-sulfur cluster biosynthesis in both prokaryotic and eukaryotic cells is
      known to be mediated by two highly conserved proteins, termed IscS and IscU in
      prokaryotes. The homodimeric IscS protein has been shown to be a cysteine
      desulfurase that catalyzes the reductive conversion of cysteine to alanine and
      sulfide. In this work, the time course of IscS-mediated Fe-S cluster assembly in
      IscU was monitored via anaerobic anion exchange chromatography. The nature and
      properties of the clusters assembled in discrete fractions were assessed via
      analytical studies together with absorption, resonance Raman, and Mossbauer
      investigations. The results show sequential cluster assembly with the initial
      IscU product containing one [2Fe-2S](2+) cluster per dimer converting first to a
      form containing two [2Fe-2S](2+) clusters per dimer and finally to a form that
      contains one [4Fe-4S](2+) cluster per dimer. Both the [2Fe-2S](2+) and [4Fe
      4S](2+) clusters in IscU are reductively labile and are degraded within minutes
      upon being exposed to air. On the basis of sequence considerations and
      spectroscopic studies, the [2Fe-2S](2+) clusters in IscU are shown to have
      incomplete cysteinyl ligation. In addition, the resonance Raman spectrum of the
      [4Fe-4S](2+) cluster in IscU is best interpreted in terms of noncysteinyl
      ligation at a unique Fe site. The ability to assemble both [2Fe-2S](2+) and [4Fe
      4S](2+) clusters in IscU supports the proposal that this ubiquitous protein
      provides a scaffold for IscS-mediated assembly of clusters that are subsequently
      used for maturation of apo Fe-S proteins.

PMID- 10891065
TI  - Proton translocation by cytochrome c oxidase can take place without the conserved
      glutamic acid in subunit I.
AB  - A glutamic acid residue in subunit I of the heme-copper oxidases is highly
      conserved and has been directly implicated in the O(2) reduction and proton
      pumping mechanisms of these respiratory enzymes. Its mutation to residues other
      than aspartic acid dramatically inhibits activity, and proton translocation is
      lost. However, this glutamic acid is replaced by a nonacidic residue in some
      structurally distant members of the heme-copper oxidases, which have a tyrosine
      residue in the vicinity. Here, using cytochrome c oxidase from Paracoccus
      denitrificans, we show that replacement of the glutamic acid and a conserved
      glycine nearby lowers the catalytic activity to <0.1% of the wild-type value. But
      if, in addition, a phenylalanine that lies close in the structure is changed to
      tyrosine, the activity rises more than 100-fold and proton translocation is
      restored. Molecular dynamics simulations suggest that the tyrosine can support a
      transient array of water molecules that may be essential for proton transfer in
      the heme-copper oxidases. Surprisingly, the glutamic acid is thus not
      indispensable, which puts important constraints on the catalytic mechanism of
      these enzymes.

PMID- 10891066
TI  - Crystal structure of 4-methyl-5-beta-hydroxyethylthiazole kinase from Bacillus
      subtilis at 1.5 A resolution.
AB  - 4-Methyl-5-beta-hydroxyethylthiazole kinase (ThiK) catalyzes the phosphorylation
      of the hydroxyl group of 4-methyl-5-beta-hydroxyethylthiazole (Thz). This enzyme
      is a salvage enzyme in the thiamin biosynthetic pathway and enables the cell to
      use recycled Thz as an alternative to its synthesis from 1-deoxy-D-xylulose-5
      phosphate, cysteine, and tyrosine. The structure of ThiK in the rhombohedral
      crystal form has been determined to 1.5 A resolution and refined to a final R
      factor of 21. 6% (R-free 25.1%). The structures of the enzyme/Thz complex and the
      enzyme/Thz-phosphate/ATP complex have also been determined. ThiK is a trimer of
      identical subunits. Each subunit contains a large nine-stranded central beta
      sheet flanked by helices. The overall fold is similar to that of ribokinase and
      adenosine kinase, although sequence similarity is not immediately apparent. The
      area of greatest similarity occurs in the ATP-binding site where several key
      residues are highly conserved. Unlike adenosine kinase and ribokinase, in which
      the active site is located between two domains within a single subunit, the ThiK
      active site it formed at the interface between two subunits within the trimer.
      The structure of the enzyme/ATP/Thz-phosphate complex suggests that phosphate
      transfer occurs by an inline mechanism. Although this mechanism is similar to
      that proposed for both ribokinase and adenosine kinase, ThiK lacks an absolutely
      conserved Asp thought to be important for catalysis in the other two enzymes.
      Instead, ThiK has a conserved cysteine (Cys198) in this position. When this Cys
      is mutated to Asp, the enzymatic activity increases 10-fold. Further sequence
      analysis suggests that another thiamin biosynthetic enzyme (ThiD), which
      catalyzes the formation of 2-methyl-4-amino-5-hydroxymethylpyrimidine
      pyrophosphate by two sequential phosphorylation reactions, belongs to the same
      family of small molecule kinases.

PMID- 10891067
TI  - Structural basis for the substrate specificity of endo-beta-N
      acetylglucosaminidase F(3).
AB  - Endo-beta-N-acetylglucosaminidase F(3) cleaves the beta(1-4) link between the
      core GlcNAc's of asparagine-linked oligosaccharides, with specificity for
      biantennary and triantennary complex glycans. The crystal structures of Endo F(3)
      and the complex with its reaction product, the biantennary octasaccharide, Gal
      beta(1-4)-GlcNAc-beta(1-2)-Man-alpha(1-3)[Gal-beta(1-4)-GlcNAc-be ta(1-2)-Man
      alpha(1-6)]-Man-beta(1-4)-GlcNAc, have been determined to 1.8 and 2.1 A
      resolution, respectively. Comparison of the structure of Endo F(3) with that of
      Endo F(1), which is specific for high-mannose oligosaccharides, reveals highly
      distinct folds and amino acid compositions at the oligosaccharide recognition
      sites. Binding of the oligosaccharide to the protein does not affect the protein
      conformation. The conformation of the oligosaccharide is similar to that seen for
      other biantennary oligosaccharides, with the exception of two links: the Gal
      beta(1-4)-GlcNAc link of the alpha(1-3) branch and the GlcNAc-beta(1-2)-Man link
      of the alpha(1-6) branch. Especially the latter link is highly distorted and
      energetically unfavorable. Only the reducing-end GlcNAc and two Man's of the
      trimannose core are in direct contact with the protein. This is in contrast with
      biochemical data for Endo F(1) that shows that activity depends on the presence
      and identity of sugar residues beyond the trimannose core. The substrate
      specificity of Endo F(3) is based on steric exclusion of incompatible
      oligosaccharides rather than on protein-carbohydrate interactions that are unique
      to complexes with biantennary or triantennary complex glycans.

PMID- 10891068
TI  - Investigations of the active site of Saccharomyces cerevisiae dolichyl-phosphate
      mannose synthase using fluorescent labeled dolichyl-phosphate derivatives.
AB  - Dolichol-phosphate mannose (Dol-P-Man) is a key mannosyl donor for the
      biosynthesis of N-linked oligosaccharides as well as for O-linked
      oligosaccharides on yeast glycoproteins, and for the synthesis of the glycosyl
      phosphatidylinositol anchor found on many cell surface glycoproteins. It is
      synthesized by Dol-P-Man synthase which is the only glycosyltransferase in the
      dolichol pathway that has been expressed as an active protein, solubilized and
      purified in large enough quantities for structural investigations. Earlier
      studies showed that the enzyme is closely associated with membranes of
      endoplasmic reticulum with unique lipid requirements for its maximal activity.
      This potential target of antibiotic therapy is now being investigated at the
      molecular level to establish information about the structure of the enzyme as
      well as determine the nature and properties of the enzyme-phospholipid
      interactions. In this paper, we have determined the activities of the fluorescent
      labeled dolichyl-phosphate derivatives as well as the intramolecular distances
      between amino acid residues near the active site and/or the fluorophores of the
      substrate derivatives using fluorescence energy resonance transfer. These results
      also show that the conserved consensus sequence is not required by Dol-P-Man
      synthase neither for the recognition of Dol-P nor for the catalytic activity.

PMID- 10891069
TI  - Spectral tuning of avian violet- and ultraviolet-sensitive visual pigments.
AB  - The violet- and ultraviolet-sensitive visual pigments of birds belong to the same
      class of pigments as the violet-sensitive (so-called blue) pigments of mammals.
      However, unlike the pigments from mammals and other vertebrate taxa which,
      depending on species, have lambda(max) values of either around 430 nm or around
      370 nm, avian pigments are found with lambda(max) values spread across this
      range. In this paper, we present the sequences of two pigments isolated from
      Humbolt penguin and pigeon with intermediate lambda(max) values of 403 and 409
      nm, respectively. By comparing the amino acid sequences of these pigments with
      the true UV pigments of budgerigar and canary and with chicken violet with a
      lambda(max) value of 420 nm, we have been able to identify five amino acid sites
      that show a pattern of substitution between species that is consistent with
      differences in lambda(max). Each of these substitutions has been introduced into
      budgerigar cDNA and expressed in vitro in COS-7 cells. Only three resulted in
      spectral shifts in the regenerated pigment; two had relatively small effects and
      may account for the spectral shifts between penguin, pigeon, and chicken whereas
      one, the replacement of Ser by Cys at site 90 in the UV pigments, produced a 35
      nm shortwave shift that could account for the spectral shift from 403 nm in
      penguin to around 370 nm in budgerigar and canary.

PMID- 10891070
TI  - Water structural changes involved in the activation process of photoactive yellow
      protein.
AB  - Fourier transform infrared (FTIR) spectroscopy was applied to the blue-light
      photoreceptor photoactive yellow protein (PYP) to investigate water structural
      changes possibly involved in the photocycle of PYP. Photointermediates were
      stabilized at low temperature, and difference IR spectra were obtained between
      intermediate states and the original state of PYP (pG). Water structural changes
      were never observed in the >3570 cm(-)(1) region for the intermediates stabilized
      at 77-250 K, such as the red-shifted pR and blue-shifted pB intermediates. In
      contrast, a negative band was observed at 3658 cm(-)(1) in the pB minus pG
      spectrum at 295 K, which shifts to 3648 cm(-)(1) upon hydration with H(2)(18)O.
      The high frequency of the O-H stretch of water indicates that the water O-H group
      does not form hydrogen bonds in pG, and newly forms these upon pB formation at
      295 K, but not at 250 K. Among 92 water molecules in the crystal structure of
      PYP, only 1 water molecule, water-200, is present in a hydrophobic core inside
      the protein. The amide N-H of Gly-7 and the imidazole nitrogen atom of His-108
      are its possible hydrogen-bonding partners, indicating that one O-H group of
      water-200 is free to form an additional hydrogen bond. The water band at 3658 cm(
      )(1) was indeed diminished in the H108F protein, which strongly suggests that the
      water band originates from water-200. Structural changes of amide bands in pB
      were much greater in the wild-type protein at 295 K than at 250 K or in the H108F
      protein at 295 K. The position of water-200 is >15 A remote from the chromophore.
      Virtually no structural changes were reported for regions larger than a few
      angstroms away from the chromophore, in the time-resolved X-ray crystallography
      experiments on pB. On the basis of the present results, as well as other
      spectroscopic observations, we conclude that water-200 (buried in a hydrophobic
      core in pG) is exposed to the aqueous phase upon formation of pB in solution. In
      neither crystalline PYP nor at low temperature is this structural transition
      observed, presumably because of the restrictions on global structural changes in
      the protein under these conditions.

PMID- 10891071
TI  - Cooperativity of a protein folding reaction probed at multiple chain positions by
      real-time 2D NMR spectroscopy.
AB  - The refolding reaction of S54G/P55N ribonuclease T1 is a two-step process, where
      fast formation of a partly folded intermediate is followed by the slow reaction
      to the native state, limited by a trans --> cis isomerization of Pro39. The
      hydrodynamic radius of this kinetic folding intermediate was determined by real
      time diffusion NMR spectroscopy. Its folding to the native state was monitored by
      a series of 128 very fast 2D (15)N-HMQC spectra, to observe the kinetics of 66
      individual backbone amide probes. We find that the intermediate is as compact as
      the native protein with many native chemical shifts. All 66 analyzed amide probes
      follow the rate-limiting prolyl isomerization, which indicates that this
      cooperative refolding reaction is fully synchronized. The stability of the
      folding intermediate was determined from the protection factors of 45 amide
      protons derived from a competition between refolding and H/D exchange. The
      intermediate has already gained 40% of the Gibbs free energy of refolding with
      many protected amides in not-yet-native regions.

PMID- 10891072
TI  - Sequential calcium binding to the regulatory domain of calcium vector protein
      reveals functional asymmetry and a novel mode of structural rearrangement.
AB  - Calcium vector protein (CaVP) from amphioxus is a two-domain, calcium-binding
      protein (18.3 kDa) of the calmodulin superfamily. Only two of the four EF-hand
      motifs (sites III and IV) have a significant binding affinity for calcium ions.
      We determined the solution structure of the domain containing these active sites
      (C-CaVP: W81-S161), in the Ca(2+)-saturated state, using NMR spectroscopy and
      restrained molecular dynamics. The tertiary structure is similar to other Ca(2+)
      binding domains containing a pair of EF-hand motifs. The apo state has
      spectroscopic and thermodynamic characteristics of a molten globule, with
      conserved secondary structure but highly fluctuating tertiary organization.
      Titration of C-CaVP with Ca(2+) revealed a stepwise ion binding, with a stable
      equilibrium intermediate in which only site III binds a calcium ion. Despite a
      highly fluctuating structure of the free site IV, the calcium-bound site III has
      a persistent structure, with similar secondary elements but different interhelix
      angle and hydrophobic packing relative to the fully calcium-saturated state.

PMID- 10891073
TI  - Synthesis and characterization of a beta-hairpin peptide that represents a 'core
      module' of bovine pancreatic trypsin inhibitor (BPTI).
AB  - A new strategy for the design and construction of peptide fragments that can
      achieve defined, nativelike secondary structure is presented. The strategy is
      based upon the hypothesis that 'core elements' of a protein, synthesized in a
      single polypeptide molecule, will favor nativelike structure, and that by
      incorporating a cross-link, nativelike core structure will dominate the ensemble
      as the more extended conformations are excluded. 'Core elements' are the elements
      of packed secondary structure that contain the slowest exchanging backbone amide
      protons in the native protein. The 'core elements' in bovine pancreatic trypsin
      inhibitor (BPTI) are the two long strands of antiparallel beta-sheet (residues 18
      24 and 29-35) and the small beta-bridge (residues 43-44). To test the design
      strategy, we synthesized an 'oxidized core module', which contains the
      antiparallel strands connected by a modified reverse turn (A27 replaced by D), a
      natural disulfide cross-link at the open end of the hairpin, and N- and C-termini
      blocking groups. A peptide with identical sequence but lacking the disulfide
      cross-link at the open end was used as the 'reduced core module' control. The
      conformational behavior of both peptides was examined using (1)H NMR
      spectroscopy. Chemical shift dispersion, chemical shift deviation from random
      coil values, sequential and long-range NOEs, and H/D amide exchange rates were
      compared for the two peptides. We conclude that the ensemble of oxidized and
      reduced core module conformations samples both nativelike 4:4 and non-native 3:5
      beta-hairpin structure, and that the oxidized module samples nativelike structure
      for a greater fraction of the time than the reduced module.

PMID- 10891074
TI  - G protein-coupled receptor activation: analysis of a highly constrained,
      "straitjacketed" rhodopsin.
AB  - G protein-coupled receptor (GPCR) activation is generally assumed to result in a
      significant structural rearrangement of the receptor, presumably involving the
      rigid body movement of transmembrane helices. We have investigated the activation
      of the GPCR rhodopsin by the construction and analysis of a mutant which contains
      a total of four disulfide bonds connecting the cytoplasmic ends of helices 1 and
      7, and 3 and 5, and the extracellular ends of helices 3 and 4, and 5 and 6.
      Despite the constraints imposed by four disulfides, this "straitjacketed"
      receptor retains the ability to activate the G protein transducin and, therefore,
      provides insight into the molecular mechanism of the initial step in signal
      transduction of this important class of receptors.

PMID- 10891075
TI  - Structure of Acinetobacter strain ADP1 protocatechuate 3, 4-dioxygenase at 2.2 A
      resolution: implications for the mechanism of an intradiol dioxygenase.
AB  - The crystal structures of protocatechuate 3,4-dioxygenase from the soil bacteria
      Acinetobacterstrain ADP1 (Ac 3,4-PCD) have been determined in space group I23 at
      pH 8.5 and 5.75. In addition, the structures of Ac 3,4-PCD complexed with its
      substrate 3, 4-dihydroxybenzoic acid (PCA), the inhibitor 4-nitrocatechol (4-NC),
      or cyanide (CN(-)) have been solved using native phases. The overall tertiary and
      quaternary structures of Ac 3,4-PCD are similar to those of the same enzyme from
      Pseudomonas putida[Ohlendorf et al. (1994) J. Mol. Biol. 244, 586-608]. At pH
      8.5, the catalytic non-heme Fe(3+) is coordinated by two axial ligands,
      Tyr447(OH) (147beta) and His460(N)(epsilon)(2) (160beta), and three equatorial
      ligands, Tyr408(OH) (108beta), His462(N)(epsilon)(2) (162beta), and a hydroxide
      ion (d(Fe-OH) = 1.91 A) in a distorted bipyramidal geometry. At pH 5.75,
      difference maps suggest a sulfate binds to the Fe(3+) in an equatorial position
      and the hydroxide is shifted [d(Fe-OH) = 2.3 A] yielding octahedral geometry for
      the active site Fe(3+). This change in ligation geometry is concomitant with a
      shift in the optical absorbance spectrum of the enzyme from lambda(max) = 450 nm
      to lambda(max) = 520 nm. Binding of substrate or 4-NC to the Fe(3+) is bidentate
      with the axial ligand Tyr447(OH) (147beta) dissociating. The structure of the 4
      NC complex supports the view that resonance delocalization of the positive
      character of the nitrogen prevents substrate activation. The cyanide complex
      confirms previous work that protocatechuate 3,4-dioxygenases have three
      coordination sites available for binding by exogenous substrates. A significant
      conformational change extending away from the active site is seen in all
      structures when compared to the native enzyme at pH 8.5. This conformational
      change is discussed in its relevance to enhancing catalysis in protocatechuate
      3,4-dioxygenases.

PMID- 10891076
TI  - Evidence for a ligand CO that is required for catalytic activity of CO
      dehydrogenase from Rhodospirillum rubrum.
AB  - Radiolabeling studies support the existence of a nonsubstrate CO ligand (CO(L))
      to the Fe atom of the proposed [FeNi] cluster of carbon monoxide dehydrogenase
      (CODH) from Rhodospirillum rubrum. Purified CODH has variable amounts of CO(L)
      dissociated depending on the extent of handling of the proteins. This dissociated
      CO(L) can be restored by incubation of CODH with CO, resulting in a 30-40%
      increase in initial activity relative to as-isolated purified CODH. A similar
      amount of CO(L) binding is observed when as-isolated purified CODH is incubated
      with (14)CO: approximately 0.33 mol of CO binds per 1 mol of CODH. Approximately
      1 mol of CO was released from CO-preincubated CODH upon denaturation of the
      protein. No CO could be detected upon denaturation of CODH that had been
      incubated with cyanide. CO(L) binds to both Ni-containing and Ni-deficient CODH,
      indicating that CO(L) is liganded to the Fe atom of the proposed [FeNi] center.
      Furthermore, the Ni in the CO(L)-deficient CODH can be removed by treatment with
      a Ni-specific chelator, dimethylglyoxime. CO preincubation protects the
      dimethylglyoxime-labile Ni, indicating that CO(L) is also involved in the
      stability of Ni in the proposed [FeNi] center.

PMID- 10891077
TI  - Thermodynamic stability of the two isoforms of bovine seminal ribonuclease.
AB  - Bovine seminal ribonuclease (BS-RNase) is a dimeric protein with two identical
      subunits linked by two disulfide bridges, each subunit showing 80% of sequence
      identity with pancreatic RNase A. BS-RNase exists in two different quaternary
      conformations in solution: the MxM form, in which each subunit exchanges its
      alpha-helical N-terminal segment with its partner, and the M=M form with no
      exchange. By differential scanning microcalorimetry (DSC), the denaturation of
      the two dimeric forms of BS-RNase was found to be more complex than a simple two
      state process. Monomeric derivatives of the dimeric protein follow instead a
      simple two-state mechanism, but are distinctly less stable than RNase A. The
      three-state N if I if D denaturation process of the two quaternary isoforms was
      interpreted by identifying in the dimers a central highly structured core,
      enclosing the covalently bonded subunit interface, which unfolds only after the
      periphery (mainly the N-terminal peptide) unfolds. Circular dichroism spectra of
      the two forms in the far-ultraviolet region show large differences between the
      secondary structure of the isoforms and that of the native BS-RNase mixture at
      equilibrium. This has been attributed to the presence in the equilibrium mixture
      of intermediate forms with displaced and disordered N-terminal alpha-helical
      segments.

PMID- 10891078
TI  - Kinetic and mechanistic studies of signal peptidase I from Escherichia coli.
AB  - Signal peptidases of prokaryotic organisms reside in the outer leaflet of the
      cytoplasmic membrane and catalyze the hydrolytic cleavage of a specific peptide
      bond of membrane-imbedded preproteins to liberate mature proteins for secretion.
      In this manuscript, we report new and efficient peptide substrates for SPase and
      their use to explore features of this enzyme's reaction mechanism. The enzyme
      used in this study was recombinant SPase I of Escherichia coli that had been
      solubilized with Triton X-100 and purified to near homogeneity. Our new
      substrates are based on the fluorogenic peptide reported by Zhong and Benkovic
      [(1998) Anal. Biochem. 255, 66], Y(NO2)FSASALA approximately KIK(Abz)-NH(2)
      (Y(NO2), 3-nitro-L-tyrosine; K(Abz), epsilon-(2-aminobenzoyl)-L-Lys; hydrolysis
      at A approximately K). We found that when a signal peptide-like sequence is
      appended onto the N-terminus of this peptide to produce K(5)-L(10)-Y(NO2)FSASALA
      approximately KIK(Abz)-NH(2), k(c)/K(m) increases from 85 to 2.5 x 10(6) M(-)(1)
      s(-)(1). k(c)/K(m) decreases with increasing concentration of Triton X-100
      micelles under the condition [Triton X-100](micelle) > [S](0) > [E](0). We
      explain this apparent inhibition with a model of surface dilution kinetics in
      which "empty" micelles compete with substrate-containing micelles for micelle
      bound enzyme. Fusion of micelle-bound enzyme with a substrate-containing micelle
      leads to formation of productive E:S substrate complexes while fusion of micelle
      bound enzyme with an "empty" micelle is nonproductive and inhibitory. The
      dependence of steady-state kinetic parameters for the SPase-catalyzed hydrolysis
      of K(5)-L(10)-Y(NO2)FSASALA approximately KIK(Abz)-NH(2) on [Triton X
      100](micelle) supports this model. Product inhibition and solvent isotope effects
      were also investigated and could be interpreted in the context of this model.

PMID- 10891079
TI  - The role of zinc in Bacillus subtilis cytidine deaminase.
AB  - Cytidine deaminase (CDA) from Bacillus subtilis is a zinc-containing enzyme
      responsible for the hydrolytic deamination of cytidine to uridine and 2'
      deoxycytidine to 2'-deoxyuridine. Titration of the cysteinyl groups of the enzyme
      with p-hydroxymercuriphenyl sulfonate (PMPS) resulted in release of one zinc ion
      per subunit. Addition of EDTA to chelate the zinc and dithiothreitol (DTT) to
      remove PMPS, followed by removal of the low molecular weight compounds by gel
      filtration, resulted in an apoenzyme with no enzymatic activity. The apoenzyme
      was almost fully reactivated by addition of zinc chloride, indicating that the
      zinc ion played a central role in catalysis, in keeping with what has been
      observed with Escherichia coli CDA [Betts, L., Xiang, S., Short, S. A.,
      Wolfenden, R., and Carter, C. W. J. (1994) J. Mol. Biol. 235, 635-656]. Addition
      of Cd(2+) or Co(2+) caused partial reactivation of the apoenzyme. Zinc
      reconstitution of the apoenzyme was strictly dependent on the presence of
      reducing agents, suggesting that the zinc-ligating cysteines, when unligated,
      participated in disulfide bond formation. An enzymatically active isoform of the
      tetrameric CDA protein, containing an extension of 13 amino acids at the C
      terminus of each subunit, was used in conjunction with the wild-type CDA in
      subunit-subunit dissociation studies to show that the zinc ion does not assist in
      the thermodynamic refolding of the protein. After treatment with PMPS and EDTA,
      the enzyme existed as unfolded unassociated subunits. Immediately following DTT
      addition to remove PMPS, the subunits refolded into a tetrameric structure,
      independent of the presence of zinc.

PMID- 10891080
TI  - Role of lys100 in human dihydroorotate dehydrogenase: mutagenesis studies and
      chemical rescue by external amines.
AB  - Chemical modification, mutagenesis, chemical rescue, and isotope effect studies
      are used to identify and probe the roles of several conserved amino acid groups
      in catalysis by human dihydroorotate dehydrogenase. Time- and pH-dependent
      inactivation of human dihydroorotate dehydrogenase by trinitrobenzenesulfonate
      implicates at least one critical lysyl residue in catalysis. Of four highly
      conserved lysines, only the cognate of Lys255 was previously suggested to have
      catalytic functionality. We now show that replacement of either Lys184 or Lys186
      by mutagenesis does not impact, whereas substitution of Lys100 abolishes,
      enzymatic activity. However, activity is partially restored to K100C (or K100A)
      by inclusion of exogenous primary amines in reaction mixtures. This rescued
      activity saturates with respect to numerous amines and exhibits a steric
      discrimination reflected in K(d,(amine)) values. For all amines, rescued k(cat)
      values were only approximately 10% of wild type and independent of amine
      basicity. K(M) values for dihydroorotate and coenzyme Q(0) were similar to wild
      type. Thus, exogenous amines (as surrogates for Lys100) apparently complement a
      chemical, not binding, step(s) of catalysis, which does not entail proton
      transfer. In support of this postulate, solvent kinetic isotope effect analysis
      indicates that Lys100 stabilizes developing negative charge on the isoalloxazine
      ring of flavin mononucleotide during hydride transfer, as has been observed for a
      number of flavoprotein oxidoreductases. Ser215 of human dihydroarotate
      dehydrogenase (DHODase) was also studied because of its alignment with the
      putative active-site base Cys130 of Lactococcus lactisDHODase. Substantial
      retention of activity by S215C, yet complete loss of activity for S215A, is
      consistent with Ser215 serving as the active-site base in the human enzyme.

PMID- 10891081
TI  - Thermodynamic and kinetic characterization of Co-C bond homolysis catalyzed by
      coenzyme B(12)-dependent methylmalonyl-CoA mutase.
AB  - Methylmalonyl-CoA mutase is a member of the family of coenzyme B(12)-dependent
      isomerases and catalyzes the 1,2-rearrangement of methylmalonyl-CoA to succinyl
      CoA. A common first step in the reactions catalyzed by coenzyme B(12)-dependent
      enzymes is cleavage of the cobalt-carbon bond of the cofactor, leading to radical
      based rearrangement reactions. Comparison of the homolysis rate for the free and
      enzyme-bound cofactors reveals an enormous rate enhancement which is on the order
      of a trillion-fold. To address how this large rate acceleration is achieved, we
      have examined the kinetic and thermodynamic parameters associated with the
      homolysis reaction catalyzed by methylmalonyl-CoA mutase. Both the rate and the
      amount of cob(II)alamin formation have been analyzed as a function of temperature
      with the protiated substrate. These studies yield the following activation
      parameters for the homolytic reaction at 37 degrees C: DeltaH(f)() = 18.8 +/- 0.8
      kcal/mol, DeltaS(f)() = 18.2 +/- 0.8 cal/(mol.K), and DeltaG(f)() = 13.1 +/- 0.6
      kcal/mol. Our results reveal that the enzyme lowers the transition state barrier
      by 17 kcal/mol, corresponding to a rate acceleration of 0.9 x 10(12)-fold. Both
      entropic and enthalpic factors contribute to the observed rate acceleration, with
      the latter predominating. The substrate binding step is exothermic, with a DeltaG
      of -5.2 kcal/mol at 37 degrees C, and is favored by both entropic and enthalpic
      factors. We have employed the available kinetic and spectroscopic data to
      construct a qualitative free energy profile for the methylmalonyl-CoA mutase
      catalyzed reaction.

PMID- 10891082
TI  - Peptidylglycine-alpha-hydroxylating monooxygenase generates two hydroxylated
      products from its mechanism-based suicide substrate, 4-phenyl-3-butenoic acid.
AB  - The bifunctional enzyme peptidylglycine-alpha-amidating monooxygenase mediates
      the conversion of C-terminal glycine-extended peptides to their active alpha
      amidated products. Peptidylglycine-alpha-hydroxylating monooxygenase (PHM, EC
      1.14.17. 3) catalyzes the first reaction in this two-step process. The olefinic
      compound 4-phenyl-3-butenoic acid (PBA) is the most potent irreversible,
      mechanism-based PHM inactivator known. While the details of the inhibitory action
      of PBA on PHM remain undefined, covalent modification of the protein has been
      proposed as the underlying mechanism. We report here that, in the process of
      inactivating PHM, PBA itself serves as a substrate without covalently labeling
      the enzyme. Approximately 100 molecules of PBA are metabolized per molecule of
      PHM inactivated, under saturating conditions. The metabolism of PBA by PHM
      generates two hydroxylated products, 2-hydroxy-4-phenyl-3-butenoic acid and its
      allylic isomer, 4-hydroxy-4-phenyl-2-butenoic acid. While one enantiomer for each
      product is significantly favored in the reaction, both are produced. From these
      observations, we conclude that hydroxylated PBA products are formed by a
      delocalized free radical mechanism and that the lack of absolute
      stereospecificity indicates significant freedom of movement within the catalytic
      site. The ability of PHM to metabolize PBA suggests that the physiological
      functions of PHM may include the hydroxylation of substrates other than those
      containing terminal glycines.

PMID- 10891083
TI  - Characterization of the elongating alpha-D-mannosyl phosphate transferase from
      three species of Leishmania using synthetic acceptor substrate analogues.
AB  - Leishmania express lipophosphoglycans and proteophosphoglycans that contain
      Galbeta1-4Manalpha1-P phosphosaccharide repeat structures assembled by the
      sequential addition of Manalpha1-P and betaGal. The synthetic acceptor substrate
      Galbeta1-4Manalpha1-P-decenyl and a series of analogues were used to probe
      Leishmania alpha-D-mannosyl phosphate transferase activity. We show that the
      activity detected with Galbeta1-4Manalpha1-P-decenyl is the elongating alpha-D
      mannosyl phosphate transferase associated with lipophosphoglycan biosynthesis
      (eMPT(LPG)). Differences in the apparent K(m) values for the donor and acceptor
      substrates were found using L. major, L. mexicana, and L. donovani promastigote
      membranes, but total activity correlated with the number of lipophosphoglycan
      repeats. Further comparisons showed that lesion-derived L. mexicana amastigotes,
      that do not express lipophosphoglycan, lack eMPT(LPG) and that nondividing L.
      major metacyclic promastigotes contain 5-fold less eMPT(LPG) activity than
      dividing procyclic promastigotes. The fine specificity of promastigote eMPT(LPG)
      activity was determined using 24 synthetic analogues of Galbeta1-4Manalpha1-P
      decenyl. The three species gave similar results: the negative charge of the
      phosphodiester and the C-6 hydroxyl of the alphaMan residue are essential for
      substrate recognition, the latter most likely acting as a hydrogen bond acceptor.
      The C-6' hydroxyl of the betaGal residue is required for substrate recognition as
      well as for catalysis. The rate of Manalpha1-P transfer declines with increasing
      acceptor substrate chain length. The presence of a monosaccharide substituent at
      the C-3 position of the terminal betaGal residue abrogates Man-P transfer,
      showing that chain elongation must precede side chain modification during
      lipophosphoglycan biosynthesis. In contrast, substitution of the penultimate
      phosphosaccharide repeat does not abrogate transfer but is slightly stimulatory
      in L. mexicana and inhibitory in L. major.

PMID- 10891084
TI  - Clustered damages and total lesions induced in DNA by ionizing radiation:
      oxidized bases and strand breaks.
AB  - Ionizing radiation induces both isolated DNA lesions and clustered damages
      multiple closely spaced lesions (strand breaks, oxidized purines, oxidized
      pyrimidines, or abasic sites within a few helical turns). Such clusters are
      postulated to be difficult to repair and thus potentially lethal or mutagenic
      lesions. Using highly purified enzymes that cleave DNA at specific classes of
      damage and electrophoretic assays developed for quantifying isolated and
      clustered damages in high molecular length genomic DNAs, we determined the
      relative frequencies of total lesions and of clustered damages involving both
      strands, and the composition and origin of such clusters. The relative frequency
      of isolated vs clustered damages depends on the identity of the lesion, with
      approximately 15-18% of oxidized purines, pyrimidines, or abasic sites in
      clusters recognized by Fpg, Nth, or Nfo proteins, respectively, but only about
      half that level of frank single strand breaks in double strand breaks. Oxidized
      base clusters and abasic site clusters constitute about 80% of complex damages,
      while double strand breaks comprise only approximately 20% of the total. The data
      also show that each cluster results from a single radiation (track) event, and
      thus clusters will be formed at low as well as high radiation doses.

PMID- 10891085
TI  - Cisplatin adducts inhibit 1,N(6)-ethenoadenine repair by interacting with the
      human 3-methyladenine DNA glycosylase.
AB  - The human 3-methyladenine DNA glycosylase (AAG) is a repair enzyme that removes a
      number of damaged bases from DNA, including adducts formed by some
      chemotherapeutic agents. Cisplatin is one of the most widely used anticancer
      drugs. Its success in killing tumor cells results from its ability to form DNA
      adducts and the cellular processes triggered by the presence of those adducts in
      DNA. Variations in tumor response to cisplatin may result from altered expression
      of cellular proteins that recognize cisplatin adducts. The present study focuses
      on the interaction between the cisplatin intrastrand cross-links and human AAG.
      Using site-specifically modified oligonucleotides containing each of the
      cisplatin intrastrand cross-links, we found that AAG readily recognized cisplatin
      adducts. The apparent dissociation constants for the 1, 2-d(GpG), the 1,2-d(ApG),
      and the 1,3-d(GpTpG) oligonucleotides were 115 nM, 71 nM, and 144 nM,
      respectively. For comparison, the apparent dissociation constant for an
      oligonucleotide containing a single 1,N(6)-ethenoadenine (epsilonA), which is
      repaired efficiently by AAG, was 26 nM. Despite the affinity of AAG for cisplatin
      adducts, AAG was not able to release any of these adducts from DNA. Furthermore,
      it was demonstrated that the presence of cisplatin adducts in the reactions
      inhibited the excision of epsilonA by AAG. These data suggest a previously
      unexplored dimension to the toxicological response of cells to cisplatin. We
      suggest that cisplatin adducts could titrate AAG away from its natural
      substrates, resulting in higher mutagenesis and/or cell death because of the
      persistence of AAG substrates in DNA.

PMID- 10891086
TI  - Suppressor mutations in Escherichia coli methionyl-tRNA formyltransferase that
      compensate for the formylation defect of a mutant tRNA aminoacylated with lysine.
AB  - The specific formylation of initiator methionyl-tRNA by methionyl-tRNA
      formyltransferase (MTF) is important for the initiation of protein synthesis in
      eubacteria such as Escherichia coli. In addition to the determinants for
      formylation present in the initiator tRNA, the nature of the amino acid attached
      to the tRNA is also important for formylation. We showed previously that a mutant
      tRNA aminoacylated with lysine was an extremely poor substrate for formylation.
      As a consequence, it was essentially inactive in initiation of protein synthesis
      in E. coli. In contrast, the same tRNA, when aminoacylated with methionine, was a
      good substrate for formylation and was, consequently, quite active in initiation.
      Here, we report on the isolation of suppressor mutations in MTF which compensate
      for the formylation defect of the mutant tRNA aminoacylated with lysine. The
      suppressor mutant has glycine 178 changed to glutamic acid. Mutants with glycine
      178 of MTF changed to aspartic acid, lysine, and leucine were generated and were
      found to be progressively weaker suppressors. Studies on allele specificity of
      suppression using different mutant tRNAs as substrates suggest that the Gly178 to
      Glu mutation compensates for the nature of the amino acid attached to the tRNA.
      We discuss these results in the framework of the crystal structure of the
      MTF.fMet-tRNA complex published recently.

PMID- 10891087
TI  - Antiferritin single-chain Fv fragment is a functional protein with properties of
      a partially structured state: comparison with the completely folded V(L) domain.
AB  - Differential scanning calorimetry and spectroscopic probes were applied to study
      folding and stability of the single-chain Fv fragment (scFv) of the anti-human
      ferritin antibody F11 and its isolated variable light-chain (V(L)) domain. The
      scFv fragment followed variable heavy-chain domain (V(H))-linker-V(L) orientation
      and contained (Gly(4)Ser)(3) linker peptide. The two proteins were produced in
      Escherichia coli and refolded from denaturant-solubilized inclusion bodies. The
      isolated V(L) domain demonstrated a typical immunoglobulin fold with well-defined
      secondary and tertiary structure and was capable of binding human ferritin with
      K(a) = 1.8 x 10(7) M(-)(1), approximately (1)/(30) of the affinity of the parent
      F11 antibody. Involvement of this V(L) domain into the two-domain scFv fragment
      yielded a distorted secondary and significantly destabilized tertiary structure
      in which neither of the two constituent domains attained complete folding. The
      thermal unfolding enthalpy of scFv F11 at pH 7.0 was as low as 5. 0 J.g(-)(1)
      versus 16.3 J.g(-)(1) obtained for the V(L) domain and 24.7 J.g(-)(1) for the
      parent F11 antibody (mouse IgG2a subclass). Intrinsic fluorescence and near
      ultraviolet circular dichroic (CD) spectra, and binding of the hydrophobic probe
      8-anilino-1-naphthalene sulfonate, confirmed partial loss of tertiary
      interactions in scFv. The spectroscopic and calorimetric properties of scFv F11
      under physiological conditions are consistent with a model of a partially
      structured state with a distorted beta-sheet as a secondary structure and partial
      loss of tertiary interactions, which closely resembles the alternatively folded A
      state adopted by an immunoglobulin at pH 2-3 [Buchner, J., Renner, M., Lilie, H.,
      Hinz, H.-J., Jaenicke, R., Kiefhaber, T., and Rudolph, R. (1991) Biochemistry 30,
      6922-6929]. However, scFv F11 demonstrated only an approximately 4-fold decrease
      in the antigen-binding affinity (K(a) = 1.3 x 10(8) M(-)(1)) versus the parent
      F11 antibody. The scFv fragment F11 provides the first description of a
      functional protein trapped under physiological conditions in a partially
      structured state. This state is either close to the native one in the antigen
      binding affinity or, alternatively, initial weak binding of the antigenic epitope
      induces folding of scFv F11 into a more structured conformation that generates
      relatively high affinity.

PMID- 10891088
TI  - A cis-proline to alanine mutant of E. coli aspartate transcarbamoylase: kinetic
      studies and three-dimensional crystal structures.
AB  - The only cis-proline residue in Escherichia coli aspartate transcarbamoylase has
      been replaced by alanine using site-specific mutagenesis. The Pro268-->Ala enzyme
      exhibits a 40-fold reduction in enzyme activity and decreased substrate affinity
      toward carbamoyl phosphate and aspartate compared to the corresponding values for
      the wild-type enzyme. The concentration of the bisubstrate analogue N
      phosphonacetyl-L-aspartate (PALA) required to activate the mutant enzyme to the
      same extent as the wild-type enzyme is significantly increased. The heterotropic
      effects of ATP and CTP upon the Pro268-->Ala enzyme are also altered. Crystal
      structures of the Pro268-->Ala enzyme in both T- and R-states show that the cis
      peptidyl linkage between Leu267 and Ala268 is maintained. However, the tertiary
      structure of both the catalytic and regulatory chains has been altered by the
      amino acid substitution, and the mobility of the active-site residues is
      increased for the R-state structure of Pro268-->Ala enzyme as comparison with the
      wild-type R-state structure. These structural changes are responsible for the
      loss of enzyme activity. Thus, Pro268 is required for the proper positioning of
      catalytically critical residues in the active site and is important for the
      formation of the high-activity high-affinity R-state of E. coli aspartate
      transcarbamoylase.

PMID- 10891089
TI  - Insensitivity of perturbed carboxyl pK(a) values in the ovomucoid third domain to
      charge replacement at a neighboring residue.
AB  - A number of carboxyl groups in turkey ovomucoid third domain (OMTKY3) have low
      pK(a) values. A previous study suggested that neighboring amino groups were
      primarily responsible for the low carboxyl pK(a) values. However, the expected
      elevation in pK(a) values for these amino groups was not observed. In the present
      study, site-directed mutagenesis is used to investigate the origins of perturbed
      carboxyl pK(a) values in OMTKY3. Electrostatic calculations suggest that Lys 34
      has large effects, 0.4-0.6 unit, on Asp 7, Glu 10, and Glu 19 which are 5-11 A
      away from Lys 34. Two-dimensional (1)H NMR techniques were used to determine
      pK(a) values of the acidic residues in OMTKY3 mutants in which Lys 34 has been
      replaced with threonine and glutamine. Surprisingly, the pK(a) values in the
      mutants are very close to those of the wild-type protein. The insensitivity of
      the acidic residues to replacement of Lys 34 suggests that long-range
      electrostatic interactions play less of a role in perturbing carboxyl pK(a)
      values than originally thought. We hypothesize that hydrogen bonds play a key
      role in perturbing some of the carboxyl ionization equilibria in OMTKY3.

PMID- 10891090
TI  - 9-cis-retinoids: biosynthesis of 9-cis-retinoic acid.
AB  - Retinoids function through conformational alterations of ligand-dependent nuclear
      transcription factors, the retinoic acid receptors, and retinoid X receptors. 9
      cis-Retinoic acid is a known biological ligand for retinoid X receptors, but its
      synthesis pathway in vivo is largely unknown. Recently, we identified a cis
      retinol dehydrogenase (cRDH) that oxidizes 9-cis-retinol to 9-cis-retinal. Since
      both the expression of cRDH mRNA and its substrate are found in liver, we studied
      9-cis-retinol metabolism and 9-cis-retinoic acid biosynthesis in two hepatic
      derived cell types, Hep G2 hepatoma cells and HSC-T6 stellate cells. Both cell
      lines accumulate similar amounts of 9-cis-retinol provided in the medium.
      However, Hep G2 cells preferentially incorporate all-trans-retinol when equimolar
      concentrations of all-trans- and 9-cis-retinol were provided. In contrast, HSC-T6
      cells did not exhibit a preference between all-trans- and 9-cis-retinol under the
      same conditions. Esterification of 9-cis-retinol occurred in both cell types,
      likely by acyl-CoA:retinol acyltransferase and lecithin:retinol acyltransferase.
      In vitro enzyme assays demonstrated that both cell types can hydrolyze 9-cis
      retinyl esters via retinyl ester hydrolase(s). In Hep G2 cells, 9-cis-retinoic
      acid synthesis was strongly inhibited by high concentrations of 9-cis-retinol,
      which may explain the low levels of 9-cis-retinol in liver of mice. Cell
      homogenates of Hep G2 can convert all-trans-retinol to 9-cis-retinal, suggesting
      that the free form of all-trans-retinol may be used as a source for 9-cis-retinol
      and, thus, 9-cis-retinoic acid synthesis. Our studies provide the basis for
      identification of additional pathways for the generation of 9-cis-retinoic acid
      in specialized tissues.

PMID- 10891091
TI  - Modulation of dimerization, binding, stability, and folding by mutation of the
      neurophysin subunit interface.
AB  - Bovine neurophysins, which have typically served as the paradigm for neurophysin
      behavior, are metastable in their disulfide-paired folded state and require
      ligand stabilization for efficient folding from the reduced state. Studies of
      unliganded porcine neurophysin (oxytocin-associated class) demonstrated that its
      dimerization constant is more than 90-fold greater than that of the corresponding
      bovine protein at neutral pH and showed that the increased dimerization constant
      is accompanied by an increase in stability sufficient to allow efficient folding
      of the reduced protein in the absence of ligand peptide. Using site-specific
      mutagenesis of the bovine protein and expression in Escherichia coli, the
      functional differences between the bovine and porcine proteins were shown to be
      attributable solely to two subunit interface mutations in the porcine protein,
      His to Arg at position 80 and Glu to Phe at position 81. Mutation of His-80 alone
      to Arg had a relatively small impact on dimerization, while mutation to either
      Glu or Asp markedly reduced dimerization in the unliganded state, albeit with
      apparent retention of the positive linkage between dimerization and binding.
      Comparison of the peptide-binding constants of the different mutants additionally
      indicated that substitution of His-80 led to modifications in binding affinity
      and specificity that were independent of effects on dimerization. The results
      demonstrate the importance of the carboxyl domain segment of the subunit
      interface in modulating neurophysin properties and suggest a specific
      contribution of the energetics of ligand-induced conformational change in this
      region to the overall thermodynamics of binding. The potential utility to future
      studies of the self-folding and monomeric mutants generated by altering the
      interface is noted.

PMID- 10891092
TI  - Mutation of W215 compromises thrombin cleavage of fibrinogen, but not of PAR-1 or
      protein C.
AB  - W215 is a highly conserved residue that shapes the S3 and S4 specificity sites of
      thrombin and participates in an edge-to-face interaction with residue F8 of the
      fibrinogen Aalpha chain. Protein C and the platelet receptor PAR-1 carry an
      acidic residue at P3 and bind to the active site of thrombin without making
      contact with W215. This suggested that mutation of W215 could dissociate the
      cleavage of fibrinogen from that of protein C and PAR-1. Replacement of W215 with
      Phe produces modest effects on thrombin function, whereas the W215Y replacement
      compromises significantly the catalytic activity toward all chromogenic and
      natural substrates that are tested. Replacement of W215 with Ala almost
      obliterates Na(+) binding, reduces the level of fibrinogen cleavage 500-fold, but
      decreases the levels of protein C activation and PAR-1 cleavage only 3- and 25
      fold, respectively. The W215A mutant cleaves PAR-1 with a specificity constant
      that is more than 13-fold higher than that of fibrinogen and protein C and is the
      first thrombin derivative to be described that functions as an almost exclusive
      activator of PAR-1. The environment of W215 influences differentially three
      physiologically important interactions of thrombin, which should assist in the
      study of each of these functions separately in vivo.

PMID- 10891093
TI  - Na(+)/H(+) exchanger NHE3 has 11 membrane spanning domains and a cleaved signal
      peptide: topology analysis using in vitro transcription/translation.
AB  - The transmembrane topology of Na(+)/H(+) exchanger NHE3 has been studied using in
      vitro transcription/translation of two types of fusion vectors designed to test
      membrane insertion properties of cDNA sequences encoding putative NHE3 membrane
      spanning domains (msds). These vectors encode N-terminal 101 (HKM0) or 139 (HKM1)
      amino acids of the H,K-ATPase alpha-subunit, a linker region and a reporter
      sequence containing five N-linked glycosylation consensus sites in the C-terminal
      177 amino acids of the H,K-ATPase beta-subunit. The glycosylation status of the
      reporter sequence was used as a marker for the analysis of signal anchor and stop
      transfer properties of each putative msd in both the HKM0 and the HKM1 vectors.
      The linker region of the vectors was replaced by sequences that contain putative
      msds of NHE3 individually or in pairs. In vitro transcription/translation was
      performed using [(35)S]methionine in a reticulocyte lysate system +/- microsomes,
      and the translation products were identified by autoradiography following
      separation using SDS-PAGE. We propose a revised NHE3 topology model, which
      contains a cleaved signal peptide followed by 11 msds, including extracellular
      orientation of the N-terminus and intracellular orientation of the C-terminus.
      The presence of a cleavable signal peptide in NHE3 was demonstrated by its
      cleavage from NHE3 during translational processing of full-length and truncated
      NHE3 in the presence of microsomes. Of 11 putative msds, six (msds 1, 2, 4, 7,
      10, and 11) acted as both signal anchor and stop transfer sequences, while five
      (msds 3, 5, 6, 8, and 9) had signal anchor activities when tested alone. Of the
      latter, 3, 5, 6, and 9 were shown to act as stop transfer sequences after C
      terminal extension. The actual membrane orientation of each sequential
      transmembrane segment of NHE3 was deduced from the membrane location of the N-
      and C-termini of NHE3. The regions between putative msds 8 and 9 and between msds
      10 and 11, which correspond to the fourth and fifth extracellular loops, did not
      act as msds when tested alone. However, the extension of the fifth extracellular
      loop with adjacent putative msds showed some membrane-associated properties
      suggesting that the fifth extracellular loop might be acting as a "P-loop"-like
      structure.

PMID- 10891094
TI  - Synthesis of compound libraries based on 3,4-diaminocyclopentanol scaffolds.

PMID- 10891095
TI  - Combinatorial approaches to the synthesis of vapor detector arrays for use in an
      electronic nose.

PMID- 10891096
TI  - Structure-based design and solid-phase parallel synthesis of phosphorylated
      nonpeptides to explore hydrophobic binding at the Src SH2 domain.
AB  - Using a novel, solid-phase parallel synthetic route and a computational docking
      program, a series of phosphorylated nonpeptides were generated to determine their
      structure-activity relationships (SAR) for binding at the SH2 domain of pp60src
      (Src). A functionalized benzoic acid intermediate was attached to solid support
      via Rink amide linkage, which upon acid cleavage generated the desired benzamide
      template-based nonpeptides in a facile manner. Compounds were synthesized using a
      combination of solid- and solution-phase techniques. Purification using reversed
      phase, semipreparative HPLC allowed for quantitative SAR studies. Specifically,
      this work focused on functional group modifications, in a parallel fashion,
      designed to explore hydrophobic binding at the pY+3 pocket of the Src SH2 domain.

PMID- 10891097
TI  - A mass spectrometry screening method for antiaggregatory activity of proteins
      covalently modified by combinatorial library members: application to sickle
      hemoglobin.
AB  - A homogeneous assay, based on electrospray mass spectrometry, is described for
      identifying compounds in a combinatorial library that covalently modify a protein
      and thereby enhance its solubility. The technique is based on measuring the
      distribution of modified proteins in the supernatant versus aggregate. Compounds
      having the greatest anti-aggregatory activity are those with the highest
      supernatant/aggregate ratio. Mass is used as a marker to identify which covalent
      modifier in the library is involved. An exploratory study is presented which
      demonstrates that the antisickling activity of a family of isothiocyanates, as
      measured by the standard C(sat) assay, correlates well (r(2) = 0.98) with the
      mass spectrometry analysis of the supernatant/aggregate distribution. The
      technique has potential for screening libraries capable of covalently modifying
      other proteins of clinical interest, e.g., Alzheimer's, Huntington's, and various
      prion related diseases.

PMID- 10891098
TI  - Solid-phase synthesis of tetrasubstituted pyrazoles, novel ligands for the
      estrogen receptor.
AB  - Most ligands for the estrogen receptor (ER) are not well suited for synthesis by
      combinatorial means, because their construction involves a series of carbon
      carbon bond forming reactions that are not uniformly high yielding. In previous
      work directed to overcoming this limitation, we surveyed various phenol
      substituted five-membered heterocycles, hoping to find a system that would afford
      both high ER binding affinity and whose synthesis could be adapted to solid-phase
      methods (Fink et al. Chem. Biol. 1999, 6, 206-219.) In this report, we have
      developed a reliable and efficient solid-phase method to prepare the best of
      these heterocycles, the tetrasubstituted pyrazoles, and we have used this
      methodology to produce small, discrete libraries of these novel ER ligands. We
      used a combination of FT-IR and nanoprobe (1)H NMR-MAS to characterize
      intermediates leading up to the final pyrazole products directly on the bead. We
      also developed a scavenging resin, which enabled us to obtain products free from
      inorganic contaminants. We prepared a 12-member test library, and then a 96
      member library, and in both cases we determined product purity and ER binding
      affinity of all of the library members. Several interesting binding affinity
      patterns have emerged from these studies, and they have provided us with new
      directions for further exploration, which has led to pyrazoles having high
      affinity and potency as agonists and antagonists toward the ER alpha subtype.

PMID- 10891099
TI  - Investigating resins for solid phase organic synthesis: the relationship between
      swelling and microenvironment as probed by EPR and fluorescence spectroscopy.
AB  - The relationship between observed swelling of two cross-linked polystyrene resins
      and the microenvironment within polymer matrixes has been examined. Polystyrene
      cross-linked with either divinyl benzene (Merrifield resin) or 1,4-bis(4
      vinylphenoxy)butane (JandaJel) was investigated with fluorescence and electron
      paramagnetic resonance spectroscopy. Fluorescence spectroscopy revealed a
      superior correlation between observed swelling and solvation effects using a
      dansyl probe with JandaJel than with Merrifield resin. However, the internal
      viscosity of pre-swollen JandaJel is higher than Merrifield resin, as determined
      by EPR measurements. The combination of these two analytical methods provides
      insights into the physical differences observed between these two chemically
      similar resins and suggests caution should be used if using singular physical
      techniques to probe the microenvironment of polymeric matrixes.

PMID- 10891100
TI  - Solid-phase synthesis of indolizidine and quinolizidine derivatives.
AB  - An efficient method for the construction of simple indolizidine and quinolizidine
      derivatives on solid support has been developed. An intramolecular tandem Michael
      reaction initiated by the nucleophilic attack of a suitably placed amino group on
      the tethered Wittig condensation products between 4- or 5-aminoaldehydes attached
      to a trityl chloride resin and 4-[(4-methylphenyl)sulfonyl]-1
      (triphenylphosphoranylidene)-2-b utanon e is the key step.

PMID- 10891101
TI  - Combinatorial liquid-phase synthesis of structurally diverse benzimidazole
      libraries.
AB  - An expedient liquid-phase synthesis for construction of the diverse benzimidazole
      libraries is described. Nucleophilic aryl substitution of poly(ethylene glycol)
      supported 4-fluoro-3-nitrobenzoic acid 3 with several primary amines under basic
      conditions, followed by Zn/NH(4)Cl mediated nitro group reduction, gave the PEG
      bound diamines 5. Subsequent cyclization of immobilized o-phenylenediamine 5
      using thiocarbonyldiimidazole (TCD) or thiophosgene in dichloromethane furnished
      benzimidazole-2-thiones 6. Treatment of 6 with alkyl halides and benzylic halides
      in the presence of triethylamine provided 1-substituted-2-alkylthio-5
      carbamoylbenzimidazoles on the support. The desired products 8 were severed from
      the PEG under mild conditions in high yield and high purity.

PMID- 10891102
TI  - Digital light-directed synthesis. A microarray platform that permits rapid
      reaction optimization on a combinatorial basis.
AB  - Solution reactions using photogenerated reagents (Gao, X.; Yu, P.; LeProust, E.;
      Sonigo, L.; Pellois, J. P.; Zhang, H. J. Am. Chem. Soc. 1998, 120, 12698) are a
      potentially powerful means for combinatorial parallel synthesis of addressable
      molecular microarrays. In this report, we demonstrate that this chemistry permits
      combinatorial screening of reaction conditions on a microarray platform. Using
      this method of optimization and our reaction apparatus, efficient photogenerated
      acids and reaction conditions suitable for removal of the acid labile protection
      group on 5'-O of nucleotides are identified in a short period of time. The
      chemistry platform demonstrated opens new avenues for rapid, simultaneous
      investigation of multiple reactions using different reagents and reaction
      parameters directly on a solid support (e.g., a glass plate). The combinatorial
      screening method described may be extended to include general organic reactions
      employing photogenerated and conventional reagents as well as a microarray
      reaction device. This should be especially valuable for efficient synthesis of
      addressable organic compound libraries.

PMID- 10891103
TI  - Peptide synthesis based on t-Boc chemistry and solution photogenerated acids.
AB  - Solution reactions using photogenerated reagents (PGRs) (Gao, X.; Yu, P. Y.;
      Leproust, E.; Sonigo, L.; Pellois, J. P.; Zhang, H. J. Am. Chem. Soc. 1998, 120,
      12698) are developed for parallel synthesis of addressable, combinatorial
      molecular microarrays. To advance the PGR chemistry for general chemical
      conversions, light-controlled synthesis of peptides, which employs photogenerated
      acids (PGAs) and/or in combination with photosensitizers for deprotection of N-t
      Boc group, is demonstrated. These reactions were performed on resin and glass
      plates and conveniently monitored by HPLC analysis (reactions on resin) and
      fluorescence emission after coupling the deprotected NH(2) group with 4(5)
      carboxyfluorescein. These results demonstrate the potential of the PGA chemistry
      for parallel synthesis of addressable peptide libraries on a microarray platform.

PMID- 10891104
TI  - Spatially addressed synthesis of amino- and amino-oxy-substituted 1, 3,5-triazine
      arrays on polymeric membranes.
AB  - Effective spatially addressed parallel assembly of trisamino- and amino-oxy-1,3,5
      triazines was achieved by applying the SPOT-synthesis technique on cellulose and
      polypropylene membranes. In addition to developing a suitable linker strategy and
      employing amines and phenolate ions as building blocks, a highly effective
      microwave-assisted nucleophilic substitution procedure at membrane-bound
      monochlorotriazines was developed. The 1,3, 5-triazines obtained could be cleaved
      in parallel from the solid support by TFA vapor to give compounds adsorbed on the
      membrane surface in a conserved spatially addressed format for analysis and
      screening. The reaction conditions developed were employed for the synthesis of
      8000 cellulose-bound 1,3,5-triazines which were probed in parallel for binding to
      the anti-transforming growth factor-alpha monoclonal antibody Tab2 in order to
      identify epitope mimics.

PMID- 10891106
TI  - Combinatorial synthesis of heterocycles: solid-phase synthesis of 2-amino-4(1H)
      quinazolinone derivatives.
AB  - A new solid-phase synthesis of various substituted 2-amino-4(1H)-quinazolinones
      from a resin bound amine component is described. The amine was readily converted
      to the corresponding polymer bound S-methylthiopseudourea. Condensation with
      different substituted isatoic anhydrides afforded 2-amino-4(1H)-quinazolinone
      derivatives. The method is amenable for combinatorial library generation.

PMID- 10891105
TI  - Solid-phase synthesis of substituted guanidines using a novel acid labile linker.
AB  - A novel acid labile linker for solid-phase synthesis of substituted guanidines
      has been developed. Its synthetic utility is exemplified by high-yielding
      pyrazole displacement with structurally and electronically diverse sets of
      aliphatic and aromatic amines. The final cleavage is achieved by treatment with
      95:5 trifluoroacetic acid/water for 1 h. The corresponding guanidines were
      obtained in high purity (80-95%) and good isolated yields (50-95%). The scope and
      limitations of this linker were further demonstrated by the solid-phase synthesis
      of an 880-member library of individual trisubstituted arylguanidines employing
      pyrazole displacement with a set of 11 anilines and two subsequent Mitsunobu N
      alkylations with sets of 10 and 8 alcohols, respectively.

PMID- 10891107
TI  - Reporter affinity labels: an o-phthalaldehyde derivative of beta-naltrexamine as
      a fluorogenic ligand for opioid receptors.

PMID- 10891108
TI  - A three-dimensional model of lanosterol 14alpha-demethylase of Candida albicans
      and its interaction with azole antifungals.
AB  - The three-dimensional structure of lanosterol 14alpha-demethylase (P450(14DM),
      CYP51) of Candida albicans was modeled on the basis of crystallographic
      coordinates of four prokaryotic P450s: P450BM3, P450cam, P450terp, and P450eryF.
      The P450(14DM) sequence was aligned to those of known proteins using a knowledge
      based alignment method. The main chain coordinates of the core regions were
      transferred directly from the corresponding coordinates of P450BM3. The side
      chain conformations of the core regions were determined by the conformations of
      the equivalent residues with the highest homologous scores in four crystal
      structures. The model was then refined using molecular mechanics and molecular
      dynamics. The reliability of the resulting model was assessed by Ramachandran
      plots, Profile-3D, hydropathy plot analysis, and by analyzing the consistency of
      the model with the experimental data. The structurally and functionally important
      residues such as the heme binding residues, the residues interacting with redox
      partner protein and/or involved in electron transfer, the residues lining
      substrate access channel, and the substrate binding residues were identified from
      the model. These residues are candidates for further site-directed mutagenesis
      and site-specific antipeptide antibody binding experiments. The active analogue
      approach was employed to search the pharmacophoric conformations for 14 azole
      antifungals. The resulting bioactive conformations were docked into the active
      site of lanosterol 14alpha-demethylase of Candida albicans. All 14 azole
      antifungals are shown to have a similar docking mode in the active site. The
      halogenated phenyl group of azole inhibitors is deep in the same hydrophobic
      binding cleft as the 17-alkyl chain of substrate. The pi-pi stacking interaction
      might exist between halogenated phenyl ring of inhibitors and the aromatic ring
      of residue Y132. The long side chains of some inhibitors such as itraconazole and
      ketoconazole surpass the active site and interact with the residues in the
      substrate access channel. To compare with mammalian enzymes, structurally
      selective residues of the active site of fungal lanosterol 14alpha-demethylase
      are distributed in the C terminus of F helix, beta6-1 sheet and beta6-2 sheet.

PMID- 10891109
TI  - Docking-based development of purine-like inhibitors of cyclin-dependent kinase-2.
AB  - The cell division cycle is controlled by cyclin-dependent kinases (cdk), which
      consist of a catalytic subunit (cdk1-cdk8) and a regulatory subunit (cyclin A-H).
      Purine-like inhibitors of cyclin-dependent kinases have recently been found to be
      of potential use as anticancer drugs. Rigid and flexible docking techniques were
      used for analysis of binding mode and design of new inhibitors. X-ray structures
      of three (ATP, olomoucine, roscovitine) cdk2 complexes were available at the
      beginning of the study and were used to optimize the docking parameters. The new
      potential inhibitors were then docked into the cdk2 enzyme, and the
      enzyme/inhibitor interaction energies were calculated and tested against the
      assayed activities of cdk1 (37 compounds) and cdk2 (9 compounds). A significant
      rank correlation between the activity and the rigid docking interaction energy
      has been found. This implies that (i) the rigid docking can be used as a tool for
      qualitative prediction of activity and (ii) values obtained by the rigid docking
      technique into the cdk2 active site can also be used for the prediction of cdk1
      activity. While the resulting geometries obtained by the rigid docking are in
      good agreement with the X-ray data, the flexible docking did not always produce
      the same inhibitor conformation as that found in the crystal.

PMID- 10891110
TI  - 6beta-Acyloxy(nor)tropanes: affinities for antagonist/agonist binding sites on
      transfected and native muscarinic receptors.
AB  - A series of esters of 6beta-hydroxynortropane and the N-methyl analogue 6beta
      tropanol were synthesized and screened versus binding of an antagonist
      (quinuclidinyl benzilate) and an agonist (oxotremorine-M) at sites on human m(1)
      , m(2)-, m(3)-, and m(4)-muscarinic receptors in transfected cell membranes and
      on native M(1)-muscarinic receptors in rat brain membranes and native M(2)
      muscarinic receptors in rat heart membranes. Most 6beta-acyloxy(nor)tropanes had
      higher affinity versus oxotremorine-M binding compared to quinuclidinyl benzilate
      binding at transfected m(1)- and native M(1)-receptors, indicative of agonist
      activity. 6beta-Acetoxynortropane had K(i) values versus oxotremorine-M binding
      at m(1)-, m(2)-, and m(4)-receptors ranging from 4 to 7 nM. N-Methylation reduced
      affinity greatly as did increasing the size of the acyl moiety. The affinity of
      6beta-benzoyloxynortropane and other analogues with larger acyl moieties was
      little affected by N-methylation or in some cases was increased. 6beta
      Acyloxy(nor)tropanes and classical muscarinic agonists, such as muscarine and
      oxotremorine, had higher affinity versus oxotremorine-M binding compared to
      quinuclidinyl benzilate binding at native M(2)-muscarinic receptors of heart, but
      not at transfected m(2)-muscarinic receptors. Antagonist/agonist binding ratios
      were not obtained for transfected m(3)-receptors, since significant oxotremorine
      M binding could not be detected. 6beta-Acyloxy(nor)tropane, two other
      (nor)tropanes, and the classical muscarinic agonists had higher affinity versus
      agonist binding compared to antagonist binding for transfected m(4)-receptors.
      The antagonist/agonist binding ratio method is clearly not always reliable for
      predicting agonist activity at muscarinic receptors.

PMID- 10891112
TI  - A novel approach for a water-soluble long-acting insulin prodrug: design,
      preparation, and analysis of [(2-sulfo)-9-fluorenylmethoxycarbonyl](3)-insulin.
AB  - In this study we designed, prepared, and analyzed a water-soluble, long-acting
      insulin derivative whose protracted action in vivo is based on a new principle
      rather than on slower absorption rates of suspended insulin formulations. To this
      end, we have prepared (9-fluorenylmethoxycarbonyl-SO(3)H)(3)-insulin ((FMS)(3)
      insulin), a derivative having three 9-fluorenylmethoxycarbonyl-SO(3)H (FMS)
      moieties covalently linked to the three amino side chains of insulin. (FMS)(3)
      insulin is soluble in aqueous buffers at neutral pH, at a concentration range of
      0.15-0.60 mM, and has about 1% of both the biological potency and the receptor
      binding affinity of the native hormone. Upon incubation at pH 7.4 and 37 degrees
      C, it undergoes a slow hydrolysis with linear regeneration of insulin possessing
      full biological potency. A single subcutaneous administration of (FMS)(3)-insulin
      to streptozocin-treated rats lowered circulating glucose levels for a prolonged
      period (t(1/2) = 30 h). Similarly, intraperitoneal administration of (FMS)(3)
      insulin to healthy rats had a prolonged glucose-lowering effect. In this
      experimental system, recovery from hypoglycemia proceeded with a t(1/2) value of
      14 +/- 1 h, as compared with t(1/2) = 8.0 +/- 1 h for native insulin and t(1/2) =
      10.0 +/- 1 h for NPH-insulin. (FMS)(3)-insulin is more resistant to proteolysis
      and appears to be nonimmunogenic. On the whole, (FMS)(3)(-)insulin represents a
      prototype version of a water-soluble, long-acting preparation of insulin. It is
      nearly inactive at the time of administration, and therefore can be administered,
      at high dose, with no concern for hypoglycemia. Because of its decreased receptor
      binding affinity, (FMS)(3)-insulin evades receptor-mediated endocytosis and
      degradation and, hence, persists for a long period in the circulation. The
      insulin constituent of the (FMS)(3)-insulin conjugate undergoes a slow,
      spontaneous activation in the circulatory system, manifesting a prolonged glucose
      lowering action in vivo. According to the data presented here, (FMS)(3)-insulin
      represents a typical prodrug: a compound which by itself shows only marginal
      activity but over time it is chemically hydrolyzed to the fully active hormone.

PMID- 10891111
TI  - 4-(3-Chloro-4-methoxybenzyl)aminophthalazines: synthesis and inhibitory activity
      toward phosphodiesterase 5.
AB  - We synthesized various 4-(3-chloro-4-methoxybenzyl)aminophthalazines substituted
      at the 1- and 6-positions and evaluated their inhibitory activity toward
      phosphodiesterase 5 (PDE5) and their vasorelaxant activity in isolated porcine
      coronary arteries precontracted with prostaglandin F2alpha (10(-5) M). The
      preferred substituents at the 1-position of the phthalazine were 4
      hydroxypiperidino, 4-hydroxymethylpiperidino, 4-(2-hydroxyethyl)piperidino, and 4
      oxopiperidino. Among these compounds, [4-(3-chloro-4-methoxybenzyl)amino-1-(4
      hydroxy)piperidino]-6-phthala zinecarbonitrile monohydrochloride (13) exhibited
      potent PDE5 inhibitory activity (IC(50) = 0.56 nM) with >1700-fold high
      selectivity over other PDE isozymes (PDE1-4). Compound 13 exhibited the most
      potent vasorelaxant action (EC(50) = 13 nM) in this series of compounds. Compound
      13 reduced mean pulmonary arterial pressure by 29.9 +/- 3.1% when administered
      intravenously at 30 microg/kg to the chronically hypoxic rats and had an apparent
      oral bioavailability of about 19.5% in rats and was selected for further
      biological evaluation.

PMID- 10891113
TI  - Structure-activity relationships of (E)-5-(2-bromovinyl)uracil and related
      pyrimidine nucleosides as antiviral agents for herpes viruses.
AB  - A series of (E)-5-(2-bromovinyl)uracil analogues and related nucleosides was
      synthesized, and their antiviral activities were evaluated. (E)-5-(2-Bromovinyl)
      2'-deoxy-L-uridine (L-BVDU, 2), 1-(beta-L-arabinofuranosyl)-(E)-5-(2
      bromovinyl)uracil (L-BVAU, 4), (E)-5-(2-bromovinyl)-1-(2-deoxy-2-fluoro-beta-L
      ribofuranosyl)uracil (L-FBVRU, 8) and (E)-5-(2-bromovinyl)-1-(2-deoxy-2-fluoro
      beta-L-arabinofuranosyl)urac il (L-FBVAU, 10) were synthesized via appropriate 5
      iodouracil analogues from L-arabinose. D- and L-Oxathiolane and -dioxolane
      derivatives 13, 16, 20, 21, and 29-34 were prepared by glycosylation reaction of
      the oxathiolane and dioxolane intermediates with silylated uracil analogues using
      TMSI as the coupling agent. The synthesized compounds were evaluated in cell
      cultures infected with the following viruses: varicella zoster virus (VZV),
      Epstein Barr virus (EBV), and herpes simplex virus types 1 and 2 (HSV-1 and HSV
      2). Among the tested compounds, beta-L-CV-OddU (29), beta-L-BV-OddU (31), and
      beta-L-IV-OddU (33) exhibited potent in vitro antiviral activity against VZV with
      EC(50) values of 0.15, 0. 07, and 0.035 microM, respectively, and against EBV
      with EC(50) values of 0.49, 0.59, and 3.91 microM, respectively.

PMID- 10891114
TI  - Aureobasidins: structure-activity relationships for the inhibition of the human
      MDR1 P-glycoprotein ABC-transporter.
AB  - Cyclic depsipeptide cyclo-[D-Hmp(1)-L-MeVal(2)-L-Phe(3)-L-MePhe(4)-L-Pro(5)-L
      aIle+ ++(6)-L-MeVal(7)-L-Leu(8)-L-betaHOMeVal(9)], the antifungal antibiotic
      aureobasidin A (AbA), was reported to interfere with ATP-binding cassette (ABC)
      transporters in yeast and mammalian cells, particularly the MDR1 P-glycoprotein
      (Pgp), a transmembrane phospholipid flippase or "hydrophobic vacuum cleaner" that
      mediates multidrug resistance (MDR) of cancer cells. In a standardized assay that
      measures Pgp function by the Pgp-mediated efflux of the calcein-AM Pgp substrate
      and uses human lymphoblastoid MDR-CEM (VBL(100)) cells as highly resistant Pgp
      expressing cells and the cyclic undecapeptide cyclosporin A (CsA) as a reference
      MDR-reversing agent (IC(50) of 3.4 microM), AbA was found to be a more active Pgp
      inhibitor (IC(50) of 2.3 microM). Out of seven natural analogues and 18 chemical
      derivatives of AbA, several were shown to display even more potent Pgp-inhibitory
      activity. The Pgp-inhibitory activity was increased about 2-fold by some minor
      modifications such as those found in the naturally occurring aureobasidins AbB
      ([D-Hiv(1)]-AbA), AbC ([Val(6)]-AbA), and AbD [gammaHOMeVal(9)]-AbA). The
      replacement of the [Phe(3)-MePhe(4)-Pro(5)] tripeptide by an 8-aminocaprylic acid
      or the N(7)()-desmethylation of MeVal(7) led to only a 3.3-fold decreased
      capacity to inhibit Pgp function, suggesting that the Pgp inhibitory potential of
      aureobasidins, though favored by the establishment of an antiparallel beta-sheet
      between the [D-Hmp(1)-L-MeVal(2)-L-Phe(3)] and [L-aIle(6)-L-MeVal(7)-L-Leu(8)-]
      tripeptides, does not critically depend on the occurrence of the [L-Phe(3)-L
      MePhe(4)-L-Pro(5)-L-aIle(6)] type II' beta-turn secondary structure. In contrast,
      the most potent Pgp inhibitors were found among AbA analogues with [betaHO
      MeVal(9)] residue alterations, with some data suggesting a negative impact of the
      [L-Leu(8)-L-betaHOMeVal(9)-D-Hmp(1)] gamma-turn secondary structure on Pgp
      inhibitory potential. The [2,3-dehydro-MeVal(9)]-AbA was the most potent Pgp
      inhibitory aureobasidin, being 13-fold more potent than AbA and 19-fold more
      potent (on a molar basis) than CsA. Finally, there was no correlation between the
      SAR for the human MDR1 Pgp inhibition and the SAR for Saccharomyces cerevisiae
      antifungal activity, which is mediated by an inositol phosphoceramide synthase
      activity.

PMID- 10891115
TI  - Synthesis and immunosuppressive activity of novel prodigiosin derivatives.
AB  - Prodigiosins (Ps) represent a family of naturally occurring red pigments
      characterized by a common pyrrolylpyrromethene skeleton. Some members of this
      family have been shown to possess interesting immunosuppressive properties
      exerted with a novel mechanism of action, different from that of currently used
      drugs. In fact, Ps inhibit phosphorylation and activation of JAK-3, a cytoplasmic
      tyrosine kinase associated with a cell surface receptor component called common
      gamma-chain, which is exclusive of all IL-2 cytokine family receptors. Blocking
      common gamma-chain transduction activity results in a potent and specific
      immunosuppressive activity. With respect to the interesting and unexploited
      immunomodulating properties of this family of compounds we initiated a medicinal
      chemistry program aimed at finding novel prodigiosin derivatives with improved
      immunosuppressive activity and lower toxicity. Utilizing an unprecedented and
      flexible way of assembling the prodigiosin frame, a number of new derivatives
      have been prepared and tested leading to the choice of 4-benzyloxy-5-[(5-undecyl
      2H-pyrrol-2-ylidene)methyl]-2, 2'-bi-1H-pyrrole (PNU-156804, 16) as a lead
      immunosuppressant.

PMID- 10891116
TI  - Synthesis and cytokine modulation properties of pyrrolo[2, 3-d]-4-pyrimidone
      nucleosides.
AB  - A series of pyrrolo[2,3-d]pyrimidone nucleosides were synthesized and evaluated
      for their ability to enhance Type 2 cytokines and to suppress Type 1 cytokines in
      human T cells activated in vitro. Compounds 16b, 16c, 16d, 18c, and 19b induced
      substantial enhancement of IL-4 (a Type 2 cytokine) levels while three compounds
      (16b, 16c, and 16f) showed significant suppression of IFNgamma (a Type 1
      cytokine) levels. The results revealed a strict structural requirement for the
      nucleoside-mediated enhancement of IL-4. Modifications of the ribofuranose moiety
      of the nucleosides either abolished or dramatically reduced the activity. Both
      the 5'-hydroxy and 5-carboxamidine are crucial for the activity. Of the few
      nucleoside analogues that demonstrated enhancement on Type 2 cytokine production,
      7-(beta-D-ribofuranosyl)pyrrolo[2, 3-d]-4-pyrimidone-5-carboxamidine (16c) showed
      a dramatic enhancement (>200%) of IL-4 levels and a significant enhancement (36%)
      of IL-5 levels. Moreover, this compound showed substantial suppression of the
      Type 1 cytokines, IFNgamma (42%), IL-2 (54%), and TNFalpha (55%). Similarly,
      compound 16b showed a substantial enhancement of IL-4 (46%) and suppression of IL
      2 (35%), IFNgamma (30%), and TNFalpha (26%). To our knowledge, these are the
      first nucleoside analogues that induce a Type 2 cytokine bias in T cells. The
      cytokine modulation property of 16c and 16b merits the therapeutic evaluation of
      these compounds in treating diseases in which immunopathology is associated with
      polarized Type 1 cytokine responses.

PMID- 10891117
TI  - QSAR model for drug human oral bioavailability.
AB  - The quantitative structure-bioavailability relationship of 232 structurally
      diverse drugs was studied to evaluate the feasibility of constructing a
      predictive model for the human oral bioavailability of prospective new medicinal
      agents. The oral bioavailability determined in human adults was assigned one of
      four ratings and analyzed in relation to physicochemical and structural factors
      by the ORMUCS (ordered multicategorical classification method using the simplex
      technique) method. A systematic examination of various physicochemical parameters
      relating primarily to absorption, and structural elements which could influence
      metabolism, was carried out to analyze their effects on the bioavailabilty
      classification of drugs in the data set. Lipophilicity, expressed as the
      distribution coefficient at pH 6.5, was found to be a significant factor
      influencing bioavailability. The observation that acids generally had better
      bioavailability characteristics than bases, with neutral compounds between, led
      to the formulation of a new parameter, Delta log D (log D(6.5) - log D(7.4)),
      which proved to be an important contributor in improving the classification
      results. The addition of 15 structural descriptors relating primarily to well
      known metabolic processes yielded a satisfactory QSAR equation which had a
      correct classification rate of 71% (97% within one class) and a Spearman rank
      correlation coefficient (R(s)) of 0.851, despite the diversity of structure and
      pharmacological activity in the compound set. In leave-one-out tests, an average
      of 67% of drugs were correctly classified (96% within one class) with an R(s) of
      0.812. The relationship formulated identified significant factors influencing
      bioavailability and assigned them quantitative values expressing their
      contribution. The predictive power of the model was evaluated using a separate
      test set of 40 compounds, of which 60% (95% within one class) were correctly
      classified. Since the necessary physicochemical parameters can be calculated or
      estimated and the structural descriptors are obtained from an inspection of the
      structure, the model enables a rough estimate to be made of the prospective human
      oral bioavailability of unsynthesized compounds. Also, the model has the
      advantage of transparency in that it indicates which factors may affect
      bioavailabilty and the extent of that effect. This could be useful in designing
      compounds which are more bioavailable. Refinement of the model is possible as
      more bioavailability data becomes available. Potential uses are in drug design,
      prioritization of compounds for synthesis, and selection for detailed studies of
      early compound leads in drug discovery programs.

PMID- 10891118
TI  - Enkephalin glycopeptide analogues produce analgesia with reduced dependence
      liability.
AB  - Endogenous peptides (e.g. enkephalins) control many aspects of brain function,
      cognition, and perception. The use of these neuroactive peptides in diverse
      studies has led to an increased understanding of brain function. Unfortunately,
      the use of brain-derived peptides as pharmaceutical agents to alter brain
      chemistry in vivo has lagged because peptides do not readily penetrate the blood
      brain barrier. Attachment of simple sugars to enkephalins increases their
      penetration of the blood-brain barrier and allows the resulting glycopeptide
      analogues to function effectively as drugs. The delta-selective glycosylated Leu
      enkephalin amide 2, H(2)N-Tyr-D-Thr-Gly-Phe-Leu-Ser(beta-D-Glc)-CONH(2), produces
      analgesic effects similar to morphine, even when administered peripherally, yet
      possesses reduced dependence liability as indicated by naloxone-precipitated
      withdrawal studies. Similar glycopeptide-based pharmaceuticals hold forth the
      promise of pain relief with improved side-effect profiles over currently
      available opioid analgesics.

PMID- 10891119
TI  - Poly(N-acryl amino acids): a new class of biologically active polyanions.
AB  - Poly(N-acryl amino acids) bearing side groups with a lipophilic character or
      having charged functional groups (i.e. -NH(2), -COOH, -SH, -OH, and phenols) were
      synthesized from the radical polymerization of N-acryl amino acid monomers.
      Monomers were prepared from the reaction of acryloyl chloride and amino acid
      esters in dry solvents. Polymers of a broad molecular weight ranging from 3 000
      to 60 000 Da were obtained. The polymers were optically active, and their
      structures were confirmed by (1)H NMR and IR spectra and elemental analysis.
      Hydroxyl-containing polymers were sulfated in high conversion yields by
      SO(3)/pyridine complex. The newly synthesized linear homopolyanions were tested
      for heparin-like activities: (i) inhibition of heparanase enzyme, (ii) release of
      basic fibroblast growth factor (bFGF) from the extracellular matrix (ECM), and
      (iii) inhibition of smooth muscle cell (SMC) proliferation. Polymers based on
      tyrosine and leucine were highly active in all three tests (microgram level).
      Polymers based on phenylalanine, tert-leucine, and proline were active as
      heparanase inhibitors and FGF release, and polymers of trans-hydroxyproline,
      glycine, and serine were active only as heparanase inhibitors. The polymer of cis
      hydroxyproline was inactive. It was found that a net anionic charge (i.e.
      carboxylic acid) is essential for biological activity. Thus, methyl ester
      derivatives of the active polymers, zwitterionic amino acid dependent groups
      (lysine, histidine), and decarboxylated amino acids (tyramine, ethanolamine) were
      inactive. The above active polymers did not exhibit anticoagulation activity
      which is considered the main limitation of heparin and heparinomimetics for
      clinical use. These synthetic poly(N-acryl amino acids) may have potential use in
      the inhibition of heparanase-mediated degradation of basement membranes
      associated with tumor metastasis, inflammation, and autoimmunity.

PMID- 10891120
TI  - Novel nonsubstrate inhibitors of human thymidine phosphorylase, a potential
      target for tumor-dependent angiogenesis.
AB  - Thymidine phosphorylase/platelet-derived endothelial cell growth factor (TP/PD
      ECGF) is an enzyme involved in thymidine metabolism and homeostasis, and its
      catalytic activity appears to play an important role in angiogenesis. Here we
      describe the cloning and expression of a His-tagged human TP/PD-ECGF and its
      assay with uracil and thymine analogues. We present the design, synthesis, and
      biological evaluation of novel 6-(phenylalkylamino)uracil derivatives which, at
      micromolar concentrations, inhibit both catabolic and anabolic reactions of human
      TP in vitro. These base analogues are not converted by the enzyme into the
      nucleoside form, thus representing pure nonsubstrate inhibitors of the enzyme.

PMID- 10891121
TI  - DELETEile chiral bidentate ligands derived from alpha-amino acids: synthetic
      applications and mechanistic considerations in the palladium-mediated asymmetric
      allylic substitutions.
AB  - A new class of chiral amidine-phosphine hybrid ligands 7a,b, which are readily
      accessible from the corresponding alpha-amino acids, were developed. A
      versatility for construction of new ligands is desirable, by which a variety of
      reactions and substrates become applicable. Indeed, a variety of modifications,
      such as exchange reactions to other amino groups in the amidine skeleton and the
      production of other types of ligands, are possible using the precursor compounds
      of 7a. Thus, novel chiral ligands 7c,d, 8, 11, and 13, which provide sterically
      and electronically different chiral circumstances, were prepared and used for the
      palladium-mediated asymmetric allylic substitutions of both acyclic and cyclic
      compounds. In these reactions, high levels of asymmetric induction were achieved
      for both substrates. A marked advancement of reactivity and enantioselectivity in
      palladium-catalyzed asymmetric allylations of 1,3-diphenylpropen-2-yl pivalate
      14a was attained by examination of electronic substituent effects in a new series
      of chiral P-N and S-N hybrid ligands 8 and 11. Mechanistic views concerning the
      enantiodiscriminating step were demonstrated, in which a good correlation between
      a novel Pr/Mr concept and the absolute configuration of allylation products are
      discussed for the prediction of enantioselecting direction. The use of ketene
      silyl acetals as nucleophiles was investigated and compared with the
      corresponding harder anionic carbon nucleophiles. The former nucleophiles
      afforded higher enantioselectivity in asymmetric allylic transformations of 14a.

PMID- 10891122
TI  - Electrocyclic ring-opening/pi-allyl cation cyclization reaction sequences
      involving gem-dihalocyclopropanes as substrates: application to syntheses of (+/
      )-, (+)-, and (-)-gamma-lycorane.
AB  - The readily prepared gem-dibromocyclopropanes (+/-)-13 and (+/-)-19 each engage
      in a silver(I)-promoted electrocyclic ring-opening/pi-allyl cation cyclization
      sequence to deliver the hexahydroindole (+/-)-20, which participates in a Suzuki
      cross-coupling reaction with arylboronic acid 3 to give the tetracyclic compound
      (+/-)-21. Catalytic hydrogenation of this last compound proceeds in a completely
      stereoselective manner to give the saturated analogue (+/-)-24, which undergoes
      Bischler-Napieralski cyclization on reaction with phosphorus oxychloride. The
      resulting lactam (+/-)-25 is then reduced with lithium aluminum hydride to give
      (+/-)-gamma-lycorane [(+/-)-1]. By using (-)-menthyl-derived carbamates 27 and
      28, this chemistry has been extended to the synthesis of the (+)- and (-)
      modifications of the title compound.

PMID- 10891123
TI  - The C-disaccharide alpha-C(1-->3)-mannopyranoside of N-acetylgalactosamine is an
      inhibitor of glycohydrolases and of human alpha-1,3-fucosyltransferase VI. Its
      epimer alpha-(1-->3)-mannopyranoside of N-acetyltalosamine is not.
AB  - The radical C-glycosidation of (-)-(1S,4R,5R, 6R)-6-endo-chloro-3-methylidene-5
      exo-(phenylseleno)-7-ox abi cyclo[2. 2.1]heptan-2-one ((-)-4) with 2,3,4, 6-tetra
      O-acetyl-alpha-D-mannopyranosyl bromide gave (+)-(1S,3R,4R, 5R,6R)-6-endo-chloro
      5-exo-(phenylseleno)-3-endo-(1',3',4', 5'-tetra-O-acetyl-2', 6'-anhydro-7'-deoxy
      D-glycero-D-manno-heptitol-7'-C-yl)-7-oxabi cyc lo[ 2.2.1]hept-2-one ((+)-5) that
      was converted into (+)-(1R,2S,5R, 6R)-5-acetamido-3-chloro-2-hydroxy-6
      (1',3',4',5'-tetra-O-acetyl)-2', 6'-anhydro-7'-deoxy-D-glycero-D-manno-heptitol
      7'-C-yl)cyclohex -3-en- 1-yl acetate ((+)-10) and into (+)-(1R,2S,5R, 6S)-5-bromo
      3-chloro-2-hydroxy-6-(1',3',4',5'-tetra-O-acetyl-2', 6'-anhydro-7'-deoxy-D
      glycero-D-manno-heptitol-7'-C-yl)cyclohex -3-en- 1-yl acetate ((+)-19).
      Ozonolysis of (+)-10 and further transformations provided 2-acetamido-2,3-dideoxy
      3-C-(2', 6'-anhydro-7'-deoxy-D-glycero-D-manno-heptitol-7'-C-yl)-D-galac tos e
      (alpha-C(1-->3)-D-mannopyranoside of N-acetylgalactosamine (alpha-D-Manp-(1-
      >3)CH(2)-D-GalNAc): 1). Displacement of the bromide (+)-19 with NaN(3) in DMF
      provided the corresponding azide ((-)-20) following a S(N)2 mechanism. Ozonolysis
      of (-)-20 and further transformations led to 2-acetamido-2,3-dideoxy-3-C-(2', 6'
      anhydro-7'-deoxy-D-glycero-D-manno-heptitol-7'-C-yl)-D-talose (alpha-C(1-->3)-D
      mannopyranoside of N-acetyl D-talosamine (alpha-D-Manp-(1-->3)CH(2)-D-TalNAc):
      2). The neutral C-disaccharide 1 inhibits several glycosidases (e.g., beta
      galactosidase from jack bean with K(i) = 7.5 microM, alpha-L-fucosidase from
      human placenta with K(i) = 28 microM, beta-glucosidase from Caldocellum
      saccharolyticum with K(i) = 18 microM) and human alpha-1, 3-fucosyltransferase VI
      (Fuc-TVI) with K(i) = 120 microM whereas it 2-epimer 2 does not. Double
      reciprocal analysis showed that the inhibition of Fuc-TVI by 1 displays a mixed
      pattern with respect to both the donor sugar GDP-fucose and the acceptor LacNAc
      with K(i) of 123 and 128 microM, respectively.

PMID- 10891124
TI  - An exploratory study of type II [3 + 4] cycloadditions between vinylcarbenoids
      and dienes.
AB  - The intramolecular type II [3 + 4] cycloaddition between vinylcarbenoids and
      furans is a practical method for the construction of 5-oxo-10
      oxatricyclo[6.2.1.0(4,9)]undeca-3, 8(11)-dienes, containing two anti-Bredt double
      bonds. These tricyclic systems are well functionalized for eventual elaboration
      to the natural product CP-263,114. The rhodium-stabilized vinylcarbenoids are
      generated by dirhodium tetracarboxylate catalyzed decomposition of
      vinyldiazoacetates. The [3 + 4] cycloaddition is generally considered to occur by
      a tandem cyclopropanation/Cope rearrangement, although evidence is presented that
      with these substrates the [3 + 4] cycloaddition may occur in a concerted manner.

PMID- 10891125
TI  - A novel octahydropyridobenzothiazepine metabolite in human urine: biomimetic
      formation from the melanogen 5-S-cysteinyldopa and formaldehyde via a peculiar
      sulfur-controlled double Pictet-Spengler condensation.
AB  - HPLC evidence is reported demonstrating the occurrence in some human urine
      samples of a novel catecholic metabolite, (3R,7S)-3, 7-dicarboxy-10,11-dihydroxy
      2,3,4,5,6,7,8,9-octahydropyrido[ 4,3-g][1, 4]benzothiazepine (2). The compound
      was shown to arise by a double Pictet-Spengler condensation of the urinary
      melanogen 5-S-cysteinyldopa (1) with formaldehyde, in which regioselective
      formation of the six-membered ring ortho to the activating hydroxyl group lends
      assistance to the subsequent closure of the seven-membered 1,4-thiazepine moiety.
      Under physiologically relevant conditions, i.e., in 0.1 M phosphate buffer pH 7.4
      and at 37 degrees C, the 7,8-tetrahydroisoquinoline 5 was the sole detectable
      intermediate in the formation of 2. N-Acetylcysteinyldopa (4) reacted likewise
      with formaldehyde to give the 7, 8-dihydroxytetrahydroisoquinoline 6. The
      anomalous regiochemistry underlying formation of 5 and 6 was rationalized with
      the aid of AM1/PM3 calculations on the model alkylthiocatechol 10, predicting a
      higher HOMO-controlled reactivity on the position ortho rather than para to the
      activating hydroxyl group. The potential of the reported chemistry as a
      convenient synthetic access to the 2,3,4, 5-tetrahydro[1,4]benzothiazepine ring
      system is suggested by the efficient conversion of the cysteinylcatechol 3 to 8
      in the presence of formaldehyde.

PMID- 10891126
TI  - Mechanism of the Photodissociation of 4-Diphenyl(trimethylsilyl)methyl-N,N
      dimethylaniline.
AB  - On irradiation in hexane (248- and 308-nm laser light) 4
      diphenyl(trimethylsilyl)methyl-N,N-dimethylaniline, 2, undergoes
      photodissociation of the C-Si bond giving 4-N,N-dimethylamino-triphenylmethyl
      radical, 3(*) (lambda(max) at 343 and 403 nm), in very high quantum yield (Phi =
      0.92). The intervention of the triplet state of 2 (lambda(max) at 515 nm) is
      clearly demonstrated through quenching experiments with 2,3-dimethylbuta-1,3
      diene, styrene, and methyl methacrylate using nanosecond laser flash photolysis
      (LFP). The formation of 3(*) is further demonstrated using EPR spectroscopy. The
      detection of the S(1) state of 2 was achieved using 266-nm picosecond LFP, and
      its lifetime was found to be 1400 ps, in agreement with the fluorescence lifetime
      (tau(f) = 1500 ps, Phi(f) = 0.085). The S(1) state is converted almost
      exclusively to the T(1) state (Phi(T) = 0.92). In polar solvents such as MeCN, 2
      undergoes (1) photoionization to its radical cation 2(*)(+), and (2)
      photodissociation of the C-Si bond, giving radical 3(*) as before in hexane. The
      formation of 2(*)(+) occurs through a two-photon process. Radical cation 2(*)(+)
      does not fragment further, as would be expected, to 3(*) via a nucleophile(MeCN)
      assisted C-Si bond cleavage but regenerates the parent compound 2. Obviously, the
      bulkiness of the triphenylmethyl group prevents interaction of 2(*)(+) with the
      solvent (MeCN) and transfer to it of the electrofugal group Me(3)Si(+). The above
      results of the laser flash photolysis are supported by pulse radiolysis,
      fluorescence measurements, and product analysis.

PMID- 10891128
TI  - Additions of Azomethine Ylides to Fullerene C(60) Assisted by a Removable Anchor.
AB  - The addition of nitrile oxides to [60]fullerene, leading to
      isoxazolinofullerenes, can be reversed using reducing agents such as Mo(CO)(6) or
      DIBALH. Thus, this reaction can be used, in principle, for
      protection/deprotection of [60]fullerene or for solubilization purposes. The
      tether-controlled tandem addition of nitrile oxides and azomethine ylides
      provides mainly cis-1 patterns. The determination of the structure of bisadducts
      was obtained by NMR spectroscopy with the help of HMQC, HMBC, and NOEDS
      techniques. The isoxazoline moiety could be removed using Mo(CO)(6) leaving a
      fulleropyrrolidine derivative.

PMID- 10891127
TI  - Stereoselective radical aryl migration from silicon to carbon.
AB  - Highly diastereoselective radical 1,5 phenyl migration reactions from silicon in
      diarylsilyl ethers to various C-centered radicals to form the corresponding 3
      phenylated alcohols are described. Functionalized aryl groups can also be
      transferred. The effect of the variation of the attacking radical on the aryl
      transfer reaction is discussed. Best results are obtained for the phenyl
      migration to nucleophilic secondary alkyl radicals, where high yields (up to 81%)
      and high selectivities (up to 95% ds) have been obtained. The mechanism of the
      process is discussed and a model to explain the stereochemical outcome of the
      reaction is presented. Finally, stereoselective 1,4 aryl migration reactions from
      Si to C, including a new method for the alpha-arylation of esters, are presented.

PMID- 10891129
TI  - Organic Thermochemistry at High ab Initio Levels. 3. A G3 Study of Cyclic
      Saturated and Unsaturated Hydrocarbons (Including Aromatics).
AB  - With the purpose of exploring the reliability of the enthalpies of formation
      calculated using the G3 method, we have examined a series of saturated and
      unsaturated alicyclic hydrocarbons varying the size and the number of formal
      double bonds in the molecule. Heats of formation have been calculated at the G3
      level through both atomization reactions and bond separation isodesmic reactions,
      and comparisons with experimental values and with values previously calculated at
      the G2(MP2) and G2 levels have been made. The quality of the G3-calculated
      enthalpies of formation using atomization reactions is comparable to that
      obtained at the G2 level using bond separation reactions, whereas G3 calculations
      are two to three times faster than G2 calculations.

PMID- 10891130
TI  - Vicinal tetrahydrofuranyl substitution of alkyl chains. Tetra-, penta-, and
      hexafunctionalized arrays.
AB  - The tetrakis (tetrahydrofuranyl) dialdehydes 14 and 19 are accessible by
      oxidative cleavage of extensively substituted cyclohexenes, which have in turn
      been assembled in a stereocontrolled manner. Reaction of 14 with an excess of the
      Normant reagent followed by ring closure resulted in conversion to the
      hexafunctionalized polyether 15. Allylindation of the same dialdehyde gave rise
      to lactol 16, a reactivity pattern that was essentially duplicated when 19 was
      treated with the Normant reagent. Attempts to add allylmagnesium bromide to 19
      resulted in operation of a Tishchenko reaction with formation of lactone 23. By
      means of X-ray diffraction analysis, it was possible to ascertain the
      conformation adopted by 20 and 23 in the solid state. In addition, 15 was shown
      to populate a conformation in which the oxygen are very predominantly in gauche
      arrangements, this structural preorganization taking place in the absence of any
      metal ions.

PMID- 10891131
TI  - PhSeSiR(3)-Catalyzed Group Transfer Radical Reactions.
AB  - A novel design for initiating radical-based chemistry in a catalytic fashion is
      described. The design of the concept is based on the phenylselenyl group transfer
      reaction from alkyl phenyl selenides by utilizing PhSeSiR(3) (1) as a catalytic
      reagent. The reaction is initiated by the homolytic cleavage of -C-Se- bond of an
      alkyl phenyl selenide by the in situ generated alkylsilyl radical (R(3)Si(*)),
      obtained by the mesolysis of PhSeSiR(3)](*)(-)( )()(1(*)(-)). The oxidative
      dimerization of counteranion PhSe(-) to PhSeSePh functions as radical terminator.
      The generation of 1(*)(-) is achieved by the photoinduced electron transfer (PET)
      promoted reductive activation of 1 through a photosystem comprising of a visible
      light (410 nm)-absorbing electron rich DMA as an electron donor and ascorbic acid
      as a co-oxidant (Figure 1). The optimum mole ratio between the catalyst 1 and
      alkyl phenyl selenides for successful reaction is established to be 1:10. The
      generality of the concept is demonstrated by carrying out variety of radical
      reactions such as cyclization (10, 15-18), intermolecular addition (25), and
      tandem annulations (32).

PMID- 10891133
TI  - Synthesis and Synthetic Application of alpha-Formylvinylphosphonates. Facile
      Synthesis of Phosphono-Substituted Heterocyclic Compounds.
AB  - The beta-ethoxy-alpha-phosphonovinyl anion, generated from beta
      (ethoxy)vinylphosphonate 1 and LDA, reacted with aldehydes and ketones or phenyl
      isocyanate to give the corresponding allylic alcohols 2a-m or 1,3-diphenyl-5
      phosphonouracil 4 in good or moderate yields. Treatment of the alcohols 2a
      d,g,h,j with trifluoroacetic acid led to alpha-formylvinylphosphonates 5a-d,g,h,j
      in excellent yields. Synthetic application of the alpha-formylvinylphosphonates
      5a-d,g,h to phosphono-substituted heterocyclic compounds was studied.

PMID- 10891132
TI  - Synthesis of the C-glycosidic analogue of adenophostin A and its uracil congener
      as potential IP(3) receptor ligands. Stereoselective construction of the C
      glycosidic structure by a temporary silicon-tethered radical coupling reaction.
AB  - Synthesis of the C-glycosidic analogue 9 of adenophostin A, a very potent IP(3)
      receptor agonist, and its uracil congener 10 was achieved via a temporary silicon
      tethered radical coupling reaction as the key step. Phenyl 3,4, 6-tri-O-(p
      methoxybenzyl)-1-seleno-beta-D-glucopyranoside (27) and 3-deoxy-3-methylene-1, 2
      O-isopropylidene-alpha-D-erythro-pentofuranose (30) were connected by a
      dimethylsilyl tether to give the radical coupling reaction substrate 24, which
      was successively treated with Bu(3)SnH/AIBN in benzene and TBAF in THF to give
      the coupling product 25 with the desired (3alpha,1'alpha)-configuration as the
      major product. From 25, the targets 9 and 10 were synthesized via introduction of
      adenine or uracil base by Vorbruggen's method and phosphorylation of the
      hydroxyls by the phosphoramidite method.

PMID- 10891134
TI  - O-Alkylation of cupferron: aiming at the design and synthesis of controlled
      nitric oxide releasing agents.
AB  - O-Alkylation of N-nitroso-N-phenylhydroxylamine ammonium salt (cupferron) was
      studied for the synthesis of novel nitric oxide (NO) releasing agents. The
      alkylation occurred regioselectively at the terminal oxygen, leading to a single
      product N-(alkyloxy)-N'-phenyldiimide N'-oxide as indicated by NMR and X-ray
      analysis. The O-alkyl derivatives exhibited significantly improved stability
      compared to their parent compound, cupferron. It was demonstrated that the
      cupferron O-alkyl derivatives could function as photoreleasing NO donor
      compounds. N-(N"-acetylphenylalanylmethylenyloxy)-N'-phenyldiimide N'-oxide),
      which linked the cupferron portion with an amino acid via an acetal moiety, was
      synthesized as an model NO prodrug where controlled NO release would occur either
      by increasing pH or by a protease-catalyzed hydrolysis.

PMID- 10891135
TI  - Palladium-Catalyzed cross-Benzannulation of Aminoenynes with Diynes. Highly
      Regioselective Synthesis of Polysubstituted Anilines.
AB  - Polysubstituted anilines were prepared by the palladium-catalyzed cross
      benzannulation of conjugated aminoenynes 1-4 with diynes 8. The reaction
      proceeded in a highly regioselective manner under mild conditions, and the
      anilines were obtained as single regioisomers. Our method complements the well
      known precedures for the preparation of polysubstituted anilines which are widely
      used in organic synthesis.

PMID- 10891136
TI  - Synthesis and Photochromism of Crowned Spirobenzothiapyran: Facilitated
      Photoisomerization by Cooperative Complexation of Crown Ether and Thiophenolate
      Moieties with Metal Ions.
AB  - Spirobenzothiapyrans bearing monoaza-12-crown-4, -15-crown-5, -18-crown-6, and
      oligooxyethylene moieties were synthesized, and their photochromism was examined
      in the presence of cations in acetonitrile. The cation complexation by their
      crown ether moieties cannot induce thermal isomerization to their corresponding
      colored merocyanine form, unlike the corresponding spirobenzopyran derivatives.
      The UV-light-induced isomerization was, however, facilitated by the cation
      complexation of the crown ether moieties and the affinity of the merocyanine
      thiophenolate anion to metal ions, especially in the presence of Li(+) and Ag(+).
      The presence of Ag(+) brought about the most remarkable effect in the
      facilitation of photoisomerization of the spirobenzothiapyrans and the thermal
      stability of the colored merocyanine form mainly due to the powerful interaction
      of the thiophenolate anion with the soft metal ion.

PMID- 10891137
TI  - Dichlorocarbene Addition to
AB  - In contrast to the terminal phosphinidene complex PhPW(CO)(5) (2), which adds to
      [5]metacyclophane (1) in a 1,4-fashion, dichlorocarbene preferentially adds in a
      1,2-fashion to the formal "anti-Bredt" type double bond of the aromatic ring of 1
      to afford the norcaradiene 11b, which immediately rearranges to the bridged
      cycloheptatriene 12b and further by a [1,5] sigmatropic chlorine migration to the
      isomeric 13b as the first observable product. More slowly, the latter isomerizes
      via a dissociative mechanism to give 15b. A computational study supports the
      notion that the [1,5] chlorine migration in the rearrangement 12b --> 13b, for
      which an activation barrier of 70.2 kJ mol(-)(1) was calculated, is essentially
      concerted with minor charge separation. In contrast, the analogous [1,5] chlorine
      migration in the flat model compound 7,7-dichlorocycloheptatriene (12a) displays
      features of a dissociative pathway.

PMID- 10891138
TI  - Studies of Diastereoselectivity in Diels-Alder Reactions of Enantiopure (SS)-2-(p
      Tolylsulfinyl)-1,4-naphthoquinone and Chiral Racemic Acyclic Dienes.
AB  - Enantiopure sulfinylnaphthoquinone (+)-5 reacted with racemic acyclic dienes 1a-f
      bearing a stereogenic allylic center, through a tandem cycloaddition/pyrolytic
      sulfoxide elimination, to afford optically enriched compounds 8a-f and 9a-f with
      good like/unlike selectivities (ca. 75:25) and good enantiomeric excesses (68
      82%), arising from the partial kinetic resolution of the racemic dienes. The
      opposite diastereoselection (8g-i: 9g-i, up to 5:95) was observed in reactions
      with dienes 1g-i, having an additional methyl group at C-3, the enantiomeric
      purities being moderate (14-25%). Steric effects and torsional interactions in
      the corresponding approaches account for the observed diastereoselectivities.

PMID- 10891139
TI  - Preparation of 1,5-disubstituted pyrrolidin-2-ones.
AB  - 1,5-Disubstituted pyrrolidin-2-ones 18a-g, 19a-h, and 20a-f were synthesized in
      good to excellent yields via the nucleophilic substitution of 5-(benzotriazol-1
      yl)-1-substituted-pyrrolidin-2-ones 9 with allylsilanes, organozinc reagents, and
      phosphorus compounds. Compounds 9 and 5-(benzotriazol-2-yl)-1-substituted
      pyrrolidin-2-one isomers 10 are readily prepared in total 70-84% yields from 2, 5
      dimethoxy-2,5-dihydrofuran (7), primary amines 8, and benzotriazole; 9 and 10
      react identically with nucleophiles.

PMID- 10891140
TI  - New Synthesis of 1,1-Substituted Hydrazines by Alkylation of N-Acyl- or N
      alkyloxycarbonylaminophthalimide Using the Mitsunobu Protocol.
AB  - N-acyl- and N-alkoxycarbonylaminophthalimides are prepared using a convenient
      reaction and are efficiently used as acid partners in Mitsunobu reaction. This
      reaction allows them to be alkylated by primary, secondary or benzyl groups.
      Comparison of the reactivities and pK(a) values of these N-substituted
      aminophthalimides suggest that the success of the Mitsunobu reaction in this case
      seems to be governed more by steric than by electronic effects. A final
      dephthaloylation step results in an efficient method for the preparation of 1,1
      substituted hydrazines.

PMID- 10891141
TI  - Rhodium-catalyzed rearrangement of alpha-diazo thiol esters to thio-substituted
      ketenes. Application in the synthesis of cyclobutanones, cyclobutenones, and beta
      lactams.
AB  - Exposure of alpha-diazo thiol esters (1) to the action of catalytic rhodium(II)
      acetate leads to a remarkably facile "thia-Wolff rearrangement", producing thio
      substituted ketenes which combine with a variety of ketenophiles to provide
      access to alpha-thiocyclobutanones, cyclobutenones, and beta-lactams. Reductive
      desulfurization of these cycloadducts takes place under mild conditions and in
      excellent yield, and this sequence thus represents a useful new alternative to
      the existing dichloroketene-based methodology for the synthesis of four-membered
      carbocycles and heterocycles.

PMID- 10891142
TI  - Syntheses of Acetylenic Oligophenylene Macrocycles Based on a Novel Dewar Benzene
      Building Block Approach.
AB  - A general synthetic approach to strained p-phenylene-based acetylenic macrocycles
      is described. A key feature in this approach is exploitation of Dewar benzene as
      an angular p-phenylene synthon. Thus, 1,4-acetal-bridged 2,5-dichloro(Dewar
      benzene) 5, prepared in four steps from dimethyl acetylenedicarboxylate and 1,2
      dichloroethylene, is applied as such a building block in the syntheses of
      strained macrocycles 13 and anti-20. For the synthesis of 13, m-phenylene units
      are used as spacers and modified Eglington-Glaser coupling is applied for the
      macrocyclization step. For the synthesis of anti-20, on the other hand, o
      phenylene units are used as spacers and Sonogashira coupling is applied for the
      macrocyclization step. Macrocycles 13 and anti-20 are characterized
      crystallographically, and their strained nature is reflected mainly in the
      deviation of the acetylene units from linearity; the C&tbd1;C-C angles range from
      168.7(3) degrees to 179.9(3) degrees in 13 and from 168.0(5) degrees to 171.4(4)
      degrees in anti-20. Macrocycle 13 shows unique conformational property, namely,
      the p-phenylene units arranged in parallel in the rectangular framework rotate
      freely about the long axes, as evidenced by the (1)H NMR studies. Macrocycle anti
      20 exhibits a Stokes shift of 179 nm, which is exceptionally large for
      phenylacetylene macrocycles, presumably owing to the characteristic stacking
      structure.

PMID- 10891143
TI  - Kinetic and theoretical studies on the mechanism of alkaline hydrolysis of DNA.
AB  - The reaction mechanism of alkaline hydrolysis of DNA has been investigated by
      kinetic analysis and density-functional-theory calculation. The rates of
      hydrolysis of thymidine 3'-monophosphate esters (including thymidylyl(3'
      5')thymidine (Tp-OT)) monotonically decrease as the leaving groups get poorer.
      According to the theoretical calculation in which the solvent effects are
      incorporated, no intermediate is formed in the course of the reaction. In the
      alkaline hydrolysis of the activated Tp-OT analogues having good leaving groups,
      the 3',5'-cyclic monophosphate of thymidine is concurrently formed through the
      intramolecular attack by the 5'-alkoxide ion. In the hydrolysis of the native
      dinucleotide, however, this side reaction does not occur, since the transition
      state leading to the departure of its poor leaving group cannot be formed due to
      conformational restraint. These arguments are supported by the theoretical
      analysis on the hydrolysis of both dimethyl phosphate and its O(bridging)-->S
      substituted analogue.

PMID- 10891144
TI  - New oxidative transformations of phenolic and indolic oxazolines: an avenue to
      useful azaspirocyclic building blocks.
AB  - The oxidative cyclization of a phenolic amide to a spirolactam has long been
      regarded as an "impossible" reaction, because exposure of the substrates to a
      variety of oxidants results in formation of spirolactones with consequent loss of
      the amine segment. We recently communicated that this heretofore unknown
      transformation may be achieved by oxidation of oxazoline analogues of phenolic
      and indolic amides. Herein, we provide full details of our work.

PMID- 10891145
TI  - Regioselective Monoalkylation of Calixarenes. Synthesis of Homodimer Calixarenes.
AB  - The selective monoalkylation at the smaller (lower) rim of the p-tert
      butylcalix[4]- and -[6]arenes using bis(butyltin)oxide and different alkylating
      agents is described. The procedure is remarkable for the mild conditions used
      allowing an efficiently access to monoalkylated calixarene derivatives in
      moderate to good yields. Monoalkynylcalix[4]arene and monoalkynylcalix[6]arene
      have been synthetically exploited for the synthesis of bis-calix[n]arenes (n = 4,
      6) with a diyne bridge by oxidative coupling of alkynes. In addition,
      intermolecular methathesis of the obtained monoalkenyl-calix[4]arene allowed the
      preparation of bis-calix[4]arene that are single bridged at the smaller (lower)
      rim with a 2-butenyl moiety.

PMID- 10891147
TI  - Solvolyses of 2-Deoxy-alpha- and beta-D-Glucopyranosyl 4'-Bromoisoquinolinium
      Tetrafluoroborates.
AB  - The solvolyses of 2-deoxy-alpha- and beta-D-glucopyranosyl 4'-bromoisoquinolinium
      tetrafluoroborates (1 and 2) were monitored in aqueous methanol, ethanol,
      trifluoroethanol, and binary mixtures of ethanol and trifluoroethanol. The
      observed rate constants are consistent with the solvolyses of 1 and 2 proceeding
      via dissociative (D(N) A(N)) transition states. In comparison to the alpha
      anomer, solvolysis of the beta-compound gives a greater transition state charge
      delocalization onto the ring oxygen atom. Analysis of the solvolysis product
      ratios indicates that the 2-deoxyglucosyl oxacarbenium ion is not solvent
      equilibrated in the solvent mixtures studied. In the solvolysis of compound 1,
      the solvent trifluoroethanol facilitates diffusional separation of the leaving
      group and, in so doing, promotes the formation of the retained trifluoroethyl
      glycoside.

PMID- 10891146
TI  - Double-helical cyclic peptides: design, synthesis, and crystal structure of
      figure-eight mirror-image conformers of adamantane-constrained cystine-containing
      cyclic peptide cyclo (Adm-Cyst)(3).
AB  - A large number of macrocycles containing alternating repeats of cystine diOMe(-NH
      CH(CO(2)Me)-CH(2)-S-)(2) and either a conformationally rigid aromatic/alicyclic
      moiety or a flexible polymethylene unit (X) in the cyclic backbone with ring size
      varying from 13- to 78-membered have been examined by spectral ((1)H NMR, FT-IR,
      CD) and X-ray crystallography studies for unusual conformational preferences.
      While (1)H NMR measurements indicated a turnlike conformation for all
      macrocycles, stabilized by intramolecular NH.CO hydrogen bonding, as also
      supported by FT-IR spectra in chloroform, convincing proof for beta-turn
      structures was provided by circular dichroism studies. Single-crystal X-ray
      studies on 39-membered cyclo (Adm-L-Cyst)(3) revealed a double-helical fold
      (figure-eight motif) for the macrocycle. Only a right-handed double helix was
      seen in the macrocycle constructed from L-cystine. The mirror-image macrocycle
      made up of D-cystine units exhibited a double helix with exactly the opposite
      screw sense, as expected. The enantiomeric figure-eights were stabilized by two
      intramolecular NH. CO hydrogen bonds and exhibited identical (1) H NMR and FT-IR
      spectra. The CD spectra of both isomers had a mirror-image relationship. The
      present results have clearly brought out the importance of cystine residues in
      inducing turn conformation that may be an important deciding factor for the
      adoption of topologically important structures by macrocycles containing multiple
      S-S linkages.

PMID- 10891148
TI  - Regio- and stereoselectivity of beta-himachalene epoxidation by m-CPBA. A
      theoretical study.

PMID- 10891149
TI  - An Efficient Access to Enantiomerically Pure Substituted Derivatives of Pipecolic
      Acid.

PMID- 10891150
TI  - Asymmetric Strecker synthesis of C-glycopeptide.

PMID- 10891151
TI  - Silver Oxide Mediated Palladium-Catalyzed Cross-Coupling Reaction of
      Cyclopropylboronic Acids with Allylic Bromides.

PMID- 10891152
TI  - Laser Flash Photolysis Measurements of the Kinetics of Ring Opening of the 2,2
      Diphenylcyclobutylcarbinyl Radical.

PMID- 10891153
TI  - A Large Accelerating Effect of Tri(tert-butyl)phosphine in the Rhodium-Catalyzed
      Addition of Arylboronic Acids to Aldehydes.

PMID- 10891154
TI  - Thermally induced isomerization of cis-1,3,4-trisubstituted 2-azetidinones.

PMID- 10891155
TI  - A New alpha-Seleno- or Nonselenoperfluoroacyl Olefination of Aldehydes and
      Ketones Using beta-Ethoxy-beta-perfluoroalkyl Vinylic Selenides.

PMID- 10891156
TI  - A one-step synthesis of 2-(2-Pyridyl)-3H-indol-3-one N-oxide: is it an efficient
      spin trap for hydroxyl radical?

PMID- 10891157
TI  - Recent reviews. 57.
AB  - Reviews are listed in order of appearance in the sources indicated. In
      multidisciplinary review journals, only those reviews which fall within the scope
      of this Journal are included. Sources are listed alphabetically in three
      categories: regularly issued review journals and series volumes, contributed
      volumes, and other monographs. Titles are numbered serially, and these numbers
      are used for reference in the index. Major English-language sources of critical
      reviews are covered. Encyclopedic treatises, annual surveys such as Specialist
      Periodical Reports, and compilations of symposia proceedings are omitted. This
      installment of Recent Reviews covers principally the early part of the 2000
      literature. Previous installment: J. Org. Chem. 2000, 65(7), 2267-76. Supporting
      Information Available: A file containing this Recent Review compilation in
      Microsoft Word and the data in rtf format. This material is available free of
      charge via the Internet at http://pubs. acs.org.

PMID- 10891158
TI  - 4-Alkoxy-2-hydroxybenzaldehyde (AHB): a versatile aldehyde linker for solid-phase
      synthesis of C-terminal modified peptides and peptidomimetics.
AB  - [reaction: see text] A new and versatile 4-alkoxy-2-hydroxybenzaldehyde (AHB)
      linker for solid-phase syntheses is described. Acylation of the polymer-bound
      secondary amine obtained from reductive amination of the aldehyde in the AHB
      linker showed good reactivity. Following acylation of the phenolic hydroxyl
      group, the resulting carboxamide resin was stable to treatment with 95% TFA. The
      O-acyl functional group was removed with 20% piperidine and the desired compound
      was cleaved from the resin by TFA treatment.

PMID- 10891159
TI  - An Efficient Procedure for the Diastereoselective Dehydration of beta-Hydroxy
      Carbonyl Compounds by CeCl(3).7H(2)O/NaI System.
AB  - The dehydration of beta-hydroxy ketones and beta-hydroxy esters is a
      synthetically useful method for the conversion of these compounds to the
      corresponding alpha,beta-unsaturated derivatives. Cerium(III) chloride
      heptahydrate in combination with sodium iodide in refluxing acetonitrile acts as
      an efficient reagent for this conversion. The present procedure, which utilizes
      cheap and "friendly" reagents, offers the corresponding (E)-enones in good yields
      as the only isolable products.

PMID- 10891160
TI  - [PtCl]
AB  - The ionic complex [PtCl(3)(C(2)H(4))](-)[(S,S)-(PhMeCH)(2)NH(2)](+) containing a
      chiral secondary amine is a new and versatile chiral derivatizing agent (CDA) for
      the determination of the enantiomeric composition of several unsaturated
      compounds including simple olefins: the diastereoisomeric mixtures arising from
      the exchange of ethylene by the unsaturated analytes are easily detected by
      (195)Pt NMR spectroscopy.

PMID- 10891161
TI  - A Facile Route to Indolo
AB  - Treatment of 1-(2'-bromobenzyl)-3,4-dihydroisoquinolines 2 in the presence of
      K(2)CO(3) in boiling DMF efficiently provided a variety of alkoxy-substituted
      indolo[2,1-a]isoquinolines 3. Application of this cyclization to 7
      benzyloxyisoquinoline derivatives, followed by further elaboration of the
      resultant 2-benzyloxy-5,6-dihydroindolo[2,1-a]isoquinolines 16a,b, led to the
      formal synthesis of dibenzopyrrocoline alkaloids, (+/-)-cryptaustoline (1a) and
      (+/-)-cryptowoline (1b).

PMID- 10891162
TI  - Allosteric silver(I) ion binding with peripheral pi clefts of a Ce(IV) double
      decker porphyrin.
AB  - [reaction: see text] A cerium(IV) double decker porphyrin (1) bearing four 4
      methoxyphenyl groups was synthesized. Compound 1 shows a positive, homotoropic
      allosteric effect in metal recognition of Ag(+) ion, and the peripheral pi clefts
      of 1 act as effective binding sites for Ag(+) ion.

PMID- 10891163
TI  - Polyaromatic Scavenger Reagents (PAHSR): A New Methodology for Rapid Purification
      in Solution-Phase Combinatorial Synthesis.
AB  - A new method of purification of solution-phase combinatorial libraries has been
      developed. Development of a chemically inert polyaromatic anchor with a reactive
      "scavenger reagent" (PAHSR) allows unreacted reagents and impurities to be
      removed from a reaction by absorption of the PAHSR to charcoal and simple
      filtration.

PMID- 10891164
TI  - Interplay of Twisting and Folding in Overcrowded Heteromerous Bistricyclic
      Aromatic Enes.
AB  - Fluorenylidenexanthenes 5-7 were synthesized by 2-fold extrusion diazo-thione
      couplings. 7 exhibited yellow crystals and purple (560 nm) solutions. (1)H NMR of
      5 and 7 indicated subtle equilibria twisted (t) right harpoon over left harpoon
      anti-folded (a) major/minor conformations. (13)C DNMR of 6 gave DeltaG(c)(double
      dagger)(enantiomerization/inversion) = 26.5 kJ/mol and DeltaG(c)(double
      dagger)(E,Z-topomerization) = 82.0 kJ/mol. PM3 calculations of 5 revealed minima
      a, t, ts (twisted/syn-folded), DeltaDeltaH(f) degrees = 0.0, 14.1, 15.6 kJ/mol,
      and transition states [t-ts], [a-ts], [t( perpendicular)], [a-a], DeltaDeltaH(f)
      degrees = 16.3, 17.4, 82.2, 99.3 kJ/mol.

PMID- 10891165
TI  - Solid-phase peptide synthesis in the reverse (N --> C) direction.
AB  - [reaction: see text] A new strategy for SPPS in the reverse direction based on
      the use of 2-Cl-trityl resin, an allyl ester as the temporary protecting group,
      and Cu(OBt)(2)/DIPCDI or HATU/DIEA as the coupling method is described. These
      conditions ensure good yields with minimal racemization of the C-terminal
      residue.

PMID- 10891166
TI  - Synthesis of chimeric oligonucleotides containing phosphodiester,
      phosphorothioate, and phosphoramidate linkages.
AB  - [reaction: see text] H-Phosphonate monomers of 2'-O-(2-methoxyethyl)
      ribonucleosides have been synthesized. Oxidation of oligonucleotide H
      phosphonates has been optimized to allow the synthesis of oligonucleotides
      containing either 2'-deoxy or 2'-O-(2-methoxyethyl) ribonucleoside residues
      combined with three different phosphate modifications in the backbone, i.e.,
      phosphodiester (PO), phosphorothioate (PS), and phosphoramidate (PN).
      Phosphodiester linkages were introduced by oxidation with a cocktail of 0.1 M
      Et(3)N in CCl(4)/Pyr/H(2)O (5:9:1) without affecting phosphorothioate or
      phosphoramidate linkages. For the synthesis of phosphoramidate-modified
      oligonucleotides, N(4)-acetyl deoxycytidine-3'-H-phosphonate monomers were used
      to avoid transamination during the oxidation step.

PMID- 10891167
TI  - Oxime Palladacycles: Stable and Efficient Catalysts for Carbon-Carbon Coupling
      Reactions.
AB  - Oxime palladacycles are thermally stable complexes not sensitive to air or
      moisture, easily prepared from very cheap materials, which can be used as
      versatile and very efficient catalysts for different carbon-carbon bond-forming
      reactions.

PMID- 10891168
TI  - Synthesis of partially modified retro and retroinverso psi[NHCH(CF(3))]-peptides.
AB  - [reaction: see text] Asymmetric conjugate additions of chiral alpha-amino esters
      to chiral 4-CF(3) Michael-acceptors were exploited to prepare a small library of
      enantiomerically pure partially modified retropeptides having a psi[NHCH(CF(3))]
      unit as a possible mimic of the classical psi(NHCO) retropeptide unit. Yields
      were nearly quantitative, and the stereoselectivity, which is controlled mainly
      by the nitrogen nucleophile, was progressively higher with increasing the steric
      bulk of the alpha-amino ester side-chain R(1).

PMID- 10891169
TI  - Intramolecular Diels-Alder Reactions of Decatrienoates: Remote Stereocontrol and
      Conformational Activation(1).
AB  - The intramolecular Diels-Alder (IMDA) reactions of C(8)-substituted
      decatrienoates have been studied. The stereospecific formation of 11 via an endo
      boat-9 transition state attests to the powerful directing influence of a C(8)
      substituent in the IMDA of decatrienoate. In addition, the contrasting
      observations that stereospecific 9 --> 11 occurs at room temperature while the
      nor-tert-butyl substrate (4a) requires 125 degrees C/5 h reaction conditions and
      produces a 60:40 mixture of diastereomers provide clear evidence that a bulky
      C(8) substituent is a powerful conformational activator of the IMDA.

PMID- 10891170
TI  - Unusual Diastereoselectivity in Intramolecular Diels-Alder Reactions of
      Substituted 3,5-Hexadienyl Acrylates. Preference for a Boatlike Structure of the
      Six-Atom Tether Due to Ester Overlap.
AB  - Thermolysis of the 3,5-hexadienyl acrylates (a) proceeds via the transition state
      E in which the connecting chain adopts a boatlike conformation due to a
      preference for maintaining ester overlap to afford the products b with good
      diastereoselectivity.

PMID- 10891171
TI  - beta-Glycosides of 2,3-Diazido-2,3-dideoxy-D-mannose, a Synthetic Precursor of a
      Rare Bacterial Cell-Wall Building Unit.
AB  - 2,3-Diazido-2,3-dideoxy-beta-D-mannopyranoside derivatives were synthesized in
      order to prepare beta-glycosides of 2,3-diacetamido-2,3-dideoxy-D-mannuronic
      acid, a rare moiety of bacterial oligosaccharides. A direct glycosyl donor, 4,6
      di-O-acetyl-2,3-diazido-2,3-dideoxy-alpha-D-mannopyranosyl bromide, was prepared,
      and its synthetic capacity was tested in glycosylation reactions. An indirect
      route was also elaborated: 3-azido-3-deoxy-beta-D-glucopyranosides were converted
      into beta-D-mannopyranosides. The cis vicinal diazido function successfully
      tolerated the conditions of mild acidic hydrolysis, tritylation, Jones oxidation,
      TEMPO oxidation, acetolysis, and bromination with TiBr(4).

PMID- 10891172
TI  - Protecting Groups for Thiols Suitable for Suzuki Conditions.
AB  - The thiol group is one of the few groups NOT tolerated by the Suzuki reaction.
      Therefore, a new protective group, the 2-methoxyisobutyryl group, was developed
      by tuning the electronic/steric properties of the acyl residue. Other thioesters,
      such as thioacetate, result in a more or less dominant side reaction, which to
      date has not been described: sulfur-assisted acylation of boronic acids. The
      reaction pathway for this new reaction is discussed.

PMID- 10891174
TI  - Indium- or Zinc-Mediated One-Pot Synthesis of Homoallylamines, beta-Amino Esters,
      and beta-Amino Nitriles.
AB  - Homoallylamines, beta-amino esters, and beta-amino nitriles were obtained in a
      one-pot synthesis directly from an aldehyde and a secondary amine such as
      dibenzylamine or diallylamine. Their condensation with titanium(IV) isopropoxide
      generates an intermediate aminoalkoxy titanium complex. Further reaction in THF
      with nucleophilic organometallic species, generated in situ from indium or zinc
      and a reactive halide (allyl bromide, alkyl bromo- or iodoacetate,
      iodoacetonitrile), furnished the corresponding amines.

PMID- 10891173
TI  - An imine addition/ring-closing metathesis approach to the spirocyclic core of
      halichlorine and pinnaic acid.
AB  - [reaction: see text] An approach to the spirocyclic core of halichlorine and
      pinnaic acid has been designed around an imine allylation/ring-closing metathesis
      sequence. This sequence has been used to generate several azabicylo[n.5] model
      systems. A newly reported metathesis catalyst was show to be highly effective for
      cyclization of these systems.

PMID- 10891175
TI  - Tandem Cyclization of Alkynylmetals Bearing a Remote Leaving Group via
      Cycloalkylidene Carbenes.
AB  - Treatment of terminal alkynes bearing a remote leaving group with MNR(2) (M = Li,
      Na, K) gives bicyclo[n.3.0]-1-alkenes (n = 3, 4). The tandem cyclization proceeds
      through a mechanism involving exo-cyclization of an alkynylmetal intermediate and
      intramolecular C-H insertion of the resulting carbenoid.

PMID- 10891176
TI  - Rapid access to synthetic lysobisphosphatidic acids using P(III) chemistry.
AB  - An expeditious route to synthetic lysobisphosphatidic acid S,S-1, its enantiomer,
      and regioisomers is reported. Synthetic difficulties concerning lipid stability
      and stereochemistry are bypassed using a phosphite triester approach in
      combination with multiple silyl protection. Spectroscopic studies evidence that
      acyl group migration in S,S-1 is accelerated by nonpolar solvents and inhibited
      by pyridine.

PMID- 10891177
TI  - Protein-degrading enediynes: library screening of Bergman cycloaromatization
      products.
AB  - [structure: see text] A screening method based on Bergman cycloaromatization
      products was applied to a compact library of estrogenic-enediyne hybrids. An
      enediyne candidate identified from the screen was subsequently synthesized, and
      it induced temperature- and concentration-dependent degradation of human estrogen
      receptor alpha upon cycloaromatization.

PMID- 10891178
TI  - A Novel, Non-High-Dilution Method for Preparation of 1,1,2,2,9,9,10,10-Octafluoro
AB  - A novel synthesis of octafluoro[2.2]paracyclophane (AF4), one that remarkably
      does not require the use of high dilution methodology, is presented. Using this
      unprecedented methodology, AF4 is produced in 60% yield in a reaction of Zn with
      0.35 M p-bis(chlorodifluoromethyl)benzene in DMA at 100 degrees C. The process
      comprises a convenient, inexpensive, and highly scaleable preparation of AF4 for
      both research and commercial purposes.

PMID- 10891179
TI  - Synthesis and characterization of oligodeoxynucleotides containing the major DNA
      adducts formed by 1,6- and 1,8-dinitropyrene.
AB  - [reaction: see text] An efficient method for the synthesis of oligonucleotides
      containing a site-specific DNA adduct formed by the carcinogens 1,6- and 1, 8
      dinitropyrene has been developed. Palladium-catalyzed amination provided a
      straightforward route for the synthesis of aminonitropyrenes which, following
      separation, were reduced to the nitrosonitropyrenes. The N
      hydroxyaminonitropyrene, generated in situ from each nitrosonitropyrene, was used
      successfully to introduce the dinitropyrene-derived DNA adduct at a defined site
      in an oligonucleotide.

PMID- 10891180
TI  - Synthesis of the alleged structure of sclerophytin A. The setting of two oxygen
      bridges within the fused cyclodecanol B ring is not Nature's Way.
AB  - [reaction: see text] The structure attributed to sclerophytin A, a cytotoxic soft
      coral metabolite, was synthesized in an enantioselective manner from (5S)-5-(d
      menthyloxy)-2(5H)-furanone. The spectral properties and polarity of the synthetic
      product require that the structural assignment to the natural material be
      revised.

PMID- 10891181
TI  - Revised constitution of sclerophytins A and B.
AB  - [structure: see text] Spectroscopic reevaluation of sclerophytin B, the acetate
      of sclerophytin A, has demonstrated unequivocally that these coral metabolites
      are not composed of two ether bridges.

PMID- 10891182
TI  - Catalytic Asymmetric Propionate Aldol Reactions via Acyl Halide-Aldehyde
      Cyclocondensations.
AB  - Catalyzed asymmetric acyl halide-aldehyde cyclocondensation (AAC) reactions
      afford highly enantiomerically enriched 3,4-disubstituted-2-oxetanones. These
      reactions constitute catalytic asymmetric propionate aldol additions. An
      optically active Al(III)-triamine complex (10 mol %) catalyzes the
      di(isopropyl)ethylamine-mediated cyclocondensation of propionyl bromide and a
      variety of aldehydes to afford beta-lactone adducts with uniformly high
      enantioselection (90 --> 98% ee), diastereoselection (74 --> 98% de), and
      chemical yields (78-90%). Lactone ring opening reveals that the enantiomerically
      enriched beta-lactones act as surrogates for syn propionate aldol adducts.

PMID- 10891183
TI  - Highly Stereoselective and Efficient Hydrosilylation of Terminal Alkynes
      Catalyzed by
AB  - With [RuCl(2)(p-cymene)](2) as a catalyst, extremely high regio- and
      stereoselectivity was observed in the hydrosilylation reaction of various
      terminal alkynes under mild conditions to afford beta-(Z)-vinylsilanes in
      excellent yields. A dramatic directing effect was also observed when alkynes
      having a hydroxyl group at the beta position to the triple bond were employed as
      a substrate, and in these cases regioisomeric alpha-vinylsilanes were generated
      with excellent selectivity.

PMID- 10891184
TI  - Asymmetric Mannich-Type Reactions of Aldimines with a Chiral Acetate.
AB  - We introduce here a strategy that enables effective addition of lithium enolates
      of acetates to aldimines. The new method depends strongly on the use of o-alkoxy
      (or o-fluoro) aniline-derived aldimines which have been found to have a potential
      effect on the enolate addition. This scope was expanded to the asymmetric process
      using the chiral acetate. A Lewis acid additive has a complementary role in the
      pronounced activation of imine functionalities.

PMID- 10891185
TI  - New Synthetic Technology for the Mild and Selective One-Carbon Homologation of
      Hindered Aldehydes in the Presence of Ketones.
AB  - A selective, mild, and highly efficient method has been uncovered during the
      total synthesis of the CP molecules to accomplish the one-carbon homologation of
      sterically hindered aldehydes in the presence of acid- and base-labile moieties,
      Michael acceptors, and even other carbonyl groups such as reactive and
      epimerizable ketones. Mechanistic studies have revealed a neutral reagent for the
      rapid collapse of cyanohydrins to ketones.

PMID- 10891187
TI  - Synthesis of the Tricyclic Skeleton of Cyathins Using Brook Rearrangement
      Mediated
AB  - The tricyclic core of cyathins has been synthesized using a Brook rearrangement
      mediated [3 + 4] annulation that we previously developed.

PMID- 10891186
TI  - Intramolecular Aryl Migration from Tin to Carbon via a Radical Atom-Transfer
      Process.
AB  - Triethylborane-induced intramolecular 1,4-aryl migration from tin to a carbon
      centered radical is described. Treatment of 3-iodoalkyldimethylphenylstannanes
      with Et(3)B in benzene at reflux followed by an addition of MeMgI provides 3
      phenylalkyltrimethylstannanes in good yield via a radical atom-transfer process.

PMID- 10891188
TI  - Asymmetric Synthesis of Axially Chiral Anilides by Enantiotopic Lithiation of
      Tricarbonyl(N-methyl-N-acyl-2,6-dimethylanilide)chromium Complex.
AB  - Axially chiral N-methylanilides were synthesized by enantioselective lithiation
      of prochiral tricarbonyl(N-methyl-N-pivaloyl-2,6-dimethylaniline)chromium (1)
      with the lithium amide of the 4-methylpiperazinylethylamine derivative 13
      followed by electrophilic quenching up to 97% ee in good yields. The resulting
      axially chiral chromium-complexd anilides 2 were oxidized under air to give the
      axially chiral anilides 14 in enantiomerically active form without axial bond
      rotation at room temperature.

PMID- 10891189
TI  - Et(3)B-Induced Hydrogermylation of Alkenes and Silyl Enol Ethers.
AB  - Tri-2-furanylgermane in the presence of a catalytic amount of Et(3)B adds to
      internal alkenes as well as terminal alkenes effectively to give the
      corresponding adducts in good to excellent yields. The addition of tri-2
      furanylgermane to silyl enol ethers followed by elimination of germyl and siloxy
      moieties provides a new route for the conversion of ketones into alkenes.

PMID- 10891190
TI  - A Concise Route to (+)-Estrone.
AB  - A concise route to the Torgov diene, the key intermediate of estrone, has been
      devised using a chiral dioxycyclopentenone as the starting material by employing
      a sequence of five steps of reactions involving a Lewis acid-mediated Diels-Alder
      reaction with Dane's diene.

PMID- 10891191
TI  - Stepwise Synthesis of Fullerene Cyclopentadienide R(5)C(60)(-) and Indenide
      R(3)C(60)(-). An Approach to Fully Unsymmetrically Substituted Derivatives.
AB  - Fullerene cyclopentadienide (PhCH(2))(2)Ph(3)C(60)(-) and indenide
      (PhCH(2))(2)PhC(60)(-), each bearing two different organic groups, were
      efficiently synthesized through regioselective reactions of 1,4-(PhCH(2))(2)C(60)
      with an organocopper reagent (PhMgBr/CuBr.SMe(2)) or a Grignard reagent (PhMgBr)
      followed by deprotonation with KO(t)()Bu.

PMID- 10891192
TI  - Synthesis and Thermal Reaction of 1,3-Bis(alkylseleno)allenes.
AB  - Reactions of Ph(2)C(3) dianion, prepared from 1,3-diphenylpropyne and n
      butyllithium, with dimethyl diselenide and benzylselenocyanate yielded 1,3
      bis(methylseleno)-1,3-diphenylpropadiene and 1,3-bis(benzylseleno)-1,3
      diphenylpropadiene, respectively, and the reaction with a mixture of dimethyl
      diselenide and benzylselenocyanate gave 1-benzylseleno-3-methylseleno-1,3
      diphenylpropadiene together with the symmetric products. Thermal reactions of the
      1,3-bis(alkylseleno)allenes afforded (E)- and (Z)-1,3,4,6-tetraphenyl-3-hexene
      1,5-diynes along with compounds derived from cyclic dimer of the allene or
      diselenide via radical pathway.

PMID- 10891193
TI  - Mechanistic Insights into the Factors Determining Exo-Endo Selectivity in the
      Lewis Acid-Catalyzed Diels-Alder Reaction of 1,3-Dienes with 2-Cycloalkenones.
AB  - We adduce evidence that the asynchronous, Lewis acid-catalyzed Diels-Alder
      reaction of 2-cycloalkenones with nonsimple alpha,beta-enones can proceed via
      transition states in which the 1,3-diene subunit is skewed, i.e., nonplanar, with
      profound effects on the ratio of exo and endo addition products.

PMID- 10891194
TI  - Synthesis of the C1-C9 fragment of callipeltoside-A.
AB  - [reaction: see text] The C1-C9 fragment of callipeltoside (17) was prepared in 12
      steps and 7.2% overall yield from bicyclic lactone (+)-4. Key steps include a
      stereoselective epoxidation and further regiocontrolled nucleophilic opening of
      the oxirane ring to install two vicinal stereocenters (C5 and C6), and the use of
      bis(trimethylsilyl) peroxide and a catalytic amount of Sn(IV) chloride for the
      chemoselective Baeyer-Villiger oxidation of unsaturated cyclopentanone 15.

PMID- 10891195
TI  - An Ammonia Equivalent for the Dimethyltitanocene-Catalyzed Intermolecular
      Hydroamination of Alkynes.
AB  - Commercially available alpha-aminodiphenylmethane 1 (benzhydrylamine) serves as a
      convenient ammonia equivalent in the dimethyltitanocene-catalyzed intermolecular
      hydroamination of alkynes. The primary formed imines can be hydrogenated and
      cleaved directly to the corresponding primary amines by catalytic hydrogenation
      using Pd/C as catalyst.

PMID- 10891196
TI  - Staudinger ligation: a peptide from a thioester and azide.
AB  - [reaction: see text] The technique of native chemical ligation enables the total
      chemical synthesis of proteins. This method is limited, however, by an absolute
      requirement for a cysteine residue at the ligation juncture. Here, this
      restriction is overcome with a new chemical ligation method in which a
      phosphinobenzenethiol is used to link a thioester and azide. The product is an
      amide with no residual atoms.

PMID- 10891197
TI  - Synthesis of Optically Active beta-Amino Acid N-Carboxyanhydrides.
AB  - Methodology has been developed for the general synthesis of optically active beta
      amino acid N-carboxyanhydrides (beta-NCAs) through cyclization of N(beta)-Boc or
      N(beta)-Cbz beta-amino acids using phosphorus tribromide. The formation of beta
      NCAs was confirmed by spectroscopy as well as an X-ray structural determination
      of beta-homoalanine-N-carboxyanhydride. The beta-NCA molecules could be
      polymerized in good yield to give optically active poly(beta-peptides) that adopt
      stable chiral conformations in solution. For example, helical oligo(L-beta
      homophenylalanine) was synthesized by polymerization of L-beta-homophenylalanine
      N-carboxyanhydride.

PMID- 10891198
TI  - Synthesis of
AB  - A series of 1,1'-dicinnamoylferrocenes were converted to the corresponding
      [3]ferrocenophane diols (4a-e) in a stereoselective manner by using samarium
      diiodide to effect the intramolecular coupling reaction, aldol reaction, and
      reduction in one-pot operation. The major reaction pathway might be derived from
      a samarium chelated transition state (I(A)()) having the moieties of s-cis enone
      and (Z)-enolate. A solid-state structure of such [3]ferrocenophane diol product
      showed that the cyclopentadienyl groups were in an eclipsed orientation and
      slightly tilted.

PMID- 10891199
TI  - A Facile Construction of the Quadranoid Skeleton: Application to the Total
      Synthesis of (+/-)-Suberosenone.
AB  - A tandem free radical cyclization-rearrangement sequence was designed and
      executed to produce tricyclo[4.3.2.0(1,5)]undecane 7 from cyclopentene 6A in a
      single operation. The total synthesis of suberosenone was accomplished from 7.

PMID- 10891200
TI  - Enantiopure Tetrahydro-beta-carbolines via Pictet-Spengler Reactions with N
      Sulfinyl Tryptamines.
AB  - The influence of N-sulfinyl chiral auxiliaries on the stereochemistry of the
      Pictet-Spengler reaction has been investigated. From enantiopure (R)-N-p
      toluenesulfinyltryptamine a new and efficient route to enantiopure tetrahydro
      beta-carbolines has been established.

PMID- 10891201
TI  - A Simple One-Pot Procedure for the Direct Conversion of Alcohols to Azides via
      Phosphate Activation.
AB  - A one-pot procedure was developed to prepare efficiently alkyl azides from
      alkanols using bis(2,4-dichlorophenyl) phosphate activation. 4
      (Dimethylamino)pyridine was used as a base, and phosphorylpyridinium azide is
      believed to be the activating agent under this condition.

PMID- 10891202
TI  - Engineering Reactions in Crystalline Solids: Radical Pairs in Crystals of Dialkyl
      1,3-Acetonedicarboxylates.
AB  - Crystalline dialkyl 1,3-acetonedicarboxylates give dialkyl succinates in high
      chemical yields by combination of alpha-carbonyl radical pairs produced by
      photochemical decarbonylation. It is proposed that the solid-state reaction
      depends on the exothermicity of two consecutive bond cleavage processes. It is
      also suggested that the efficiency of radical formation in the solid state is
      determined by the effect of substituents on bond dissociation energies and
      radical-stabilization abilities.

PMID- 10891203
TI  - A novel three-component one-pot pyrimidine synthesis based upon a coupling
      isomerization sequence.
AB  - [reaction: see text] 2,4,6-Tri(hetero)aryl-substituted pyrimidines can be readily
      synthesized in a three-component one-pot process based upon a coupling
      isomerization sequence of an electron-poor (hetero)aryl halide and a terminal
      propargyl alcohol subsequently followed by a cyclocondensation with amidinium
      salts.

PMID- 10891204
TI  - Enantioselective Ring Opening of Aza and Oxabicyclic Alkenes with Dimethylzinc.
AB  - A system for efficient, asymmetric alkylative ring opening of
      azabenzonorbornadienes and [2.2.1] and [3.2.1] oxabicyclic alkenes was developed.
      The use of Pd(CH(3)CN)(2)Cl(2) and chiral phosphinooxazoline ligands gives the
      dihydronaphthalenes, cyclohexenols, and cycloheptenols in excellent yields and
      enantiomeric excesses.

PMID- 10891205
TI  - Bis(2,2,2-trifluoroethyl)bromophosphonoacetate, a Novel HWE Reagent for the
      Preparation of (E)-alpha-Bromoacrylates: A General and Stereoselective Method for
      the Synthesis of Trisubstituted Alkenes.
AB  - A novel reagent, methyl bis(2,2,2-trifluoroethoxy)bromophosphonoacetate (3a), was
      designed and prepared in order to efficiently synthesize (E)-alpha
      bromoacrylates, which are useful precursors for various C-C bond formations.
      Honer-Wadsworth-Emmons (HWE) reaction of various aldehydes with 3a in the
      presence of t-BuOK and 18-C-6 gave the corresponding (E)-alpha-bromoacrylate
      derivatives with high stereoselectivity. Using the (E)-alpha-bromoacrylate as a
      key intermediate, a general stereoselective synthesis of trisubstituted alkenes
      via Pd-catalyzed cross-coupling was developed.

PMID- 10891206
TI  - Steric Effects in Photoinduced Electron Transfer Reaction of Halogenated 1,4
      Benzoquinones with Donor Olefins.
AB  - The photoinduced electron transfer reaction of halogenated 1,4-benzoquinones with
      2,3-dimethyl-2-butene or 3,4-dimethyl-2-pentene gave the primary, secondary, and
      tertiary monoallyl ethers of hydroquinones, with the product distributions highly
      dependent on the steric nature of quinones and olefins.

PMID- 10891207
TI  - Synthesis of (-)-Lasubine(I) via a Planar Chiral (eta(6)-Arene)Cr(CO)(3)]
      Complex.

PMID- 10891209
TI  - Baeyer-Villiger Oxidation Promoted by Reaction of Peracids with Cyclic
      Oxocarbenium Ions Generated in Situ from Internal Hemiketals.

PMID- 10891208
TI  - Gram-Scale Synthesis of (+)-Discodermolide.

PMID- 10891210
TI  - A year of firsts for organic letters

PMID- 10891212
TI  - Synthesis of Copper(I) catenanes incorporating a disulfide bridge and their
      deposition on a gold surface
AB  - The synthesis of two coordinating catenates with the ability to undergo surface
      confined chemistry is described. For each catenate, one of the rings includes a
      2,9-diphenyl-1,10-phenanthroline unit as a coordinating moiety and a disulfide
      bridge, which allows adsorption of the catenate onto a gold surface, thus going
      from a molecular catenate to a [gold-adsorbed] species in which gold atoms are
      elements of one of the rings.

PMID- 10891211
TI  - The first syntheses of the 1-oxo-2-oxa-5-azaspiro[3.4]octane ring system found in
      oxazolomycin.
AB  - [reaction: see text] L-Proline was utilized to prepare an optically active 1-oxo
      2-oxa-5-azaspiro[3.4]octane for the first time. The synthesis of the racemic
      system, using a tandem aldol-lactonization reaction, is also described. Ruthenium
      tetroxide oxidation of these compounds afforded the corresponding spiro beta
      lactone gamma-lactams.

PMID- 10891213
TI  - A cavitand-porphyrin hybrid.
AB  - [structure: see text] Host-guest complexes of a new open-ended cavitand show
      unprecedented stabilities. Simultaneous binding in the cavity and at the
      metalloporphyrin affects both the kinetics and the thermodynamics of caviplex
      formation.

PMID- 10891214
TI  - Induced circular dichroism of cyclodextrin inclusion complexes: examining the
      cavity with a bilateral probe
AB  - The induced circular dichroism (ICD) of 1@7-Cy gives rise to an unusual spectrum
      which can be explained by a positive and a negative contribution of two identical
      chromophores. This finding is in agreement with rules predicting the ICD of
      chiral supramolecular systems.

PMID- 10891216
TI  - Hydrogen bonds in carboxylic acid-carboxylate systems in solution. 1. In
      anhydrous, aprotic media
AB  - Preliminary NMR studies on hydrogen bonding of carboxylic acid-carboxylate
      systems in an anhydrous, aprotic solvent are presented. In all cases, a low-field
      resonance (16-20 ppm) indicative of strong hydrogen bonding was observed. From
      these results, it seems probable that this characteristic downfield shift should
      be exhibited by all carboxylic acid-carboxylate systems in anhydrous, aprotic
      media.

PMID- 10891215
TI  - Synthesis of a six-carbon sialic acid using an indium-mediated coupling.
AB  - [reaction: see text] The synthesis of a six-carbon truncated sialic acid is
      described. A key step in the synthesis was an indium-mediated allyl addition to a
      serine-derived aldehyde. Careful choice of protecting groups was found to be
      necessary in order to prevent unwanted side reactions throughout the sequence.
      The truncated sialic acid was obtained in a form suitable for activation as a
      glycosyl donor.

PMID- 10891217
TI  - Cyclization of alkenyl radicals in 5- and 6-(pi-Exo)-exo-dig modes: new entry to
      exo-cyclic dienes
AB  - Radical cyclizations of alkenyl iodides in both 5- and 6-(pi-exo)-exo-dig modes
      were effected by tributyltin hydride and AIBN to give exo-cyclic dienes fused to
      five- and six-membered rings in good yields.

PMID- 10891218
TI  - Unique synthetic utility of BF(3).OEt(2) in the highly diastereoselective
      reduction of hydroxy carbonyl and dicarbonyl substrates
AB  - A new aspect of commonly used BF(3).OEt(2) has been illuminated by successfully
      demonstrating the unique but highly stereoselective reactions of hydroxy carbonyl
      and dicarbonyl substrates. For example, treatment of gamma-hydroxy ketone 1c with
      BF(3).OEt(2)/Bu(3)SnH in CH(2)Cl(2) at -78 to -40 degrees C afforded the
      corresponding 1, 4-diol 2c with virtually complete diastereoselection, while use
      of TiCl(4) as a Lewis acid under similar reaction conditions caused a total lack
      of diol yield and selectivity (17%; 2c/3c = 1.2:1), accompanied by a significant
      formation of 2,3-disubstituted tetrahydrofuran 4 (44%).

PMID- 10891219
TI  - Copper-mediated cross-coupling of aryl boronic acids and alkyl thiols.
AB  - [reaction: see text] The cross-coupling of aryl boronic acids and alkanethiols
      mediated by copper(II) acetate and pyridine in anhydrous dimethylformamide
      affords aryl alkyl sulfides in good yield with a wide variety of substituted aryl
      boronic acids. The method is applicable to the synthesis of aryl sulfides of
      cysteine.

PMID- 10891220
TI  - Annulation reactions of allene-derived 1,3-dipole with 3-substituted-chromones:
      unusual recognition of 4pi-component in 3-(N-Aryliminomethyl)chromones through
AB  - All-carbon dipole derived by the interaction of triphenylphosphine with allenic
      ester is able to locate the polarized 2pi-component in 3-formylchromones through
      a regioselective [2 + 3] addition to the C2-C3 pi-bond, which is followed by
      deformylation leading to novel 3a,9a-dihydro-1-ethoxycarbonyl-1-cyclopenteno[5, 4
      b]benzopyran-4-ones. On the contrary, the dipole recognizes azadiene in 3-(N
      aryliminomethyl)chromones through [4 + 3] annulation and initially formed adducts
      undergo tandem rearrangements to afford novel N-aryl-2, 3-dihydro-4
      ethoxycarbonylchromano[2,3-b]azepine-6-ones in good yield.

PMID- 10891221
TI  - Substrate mimetics and freezing strategy: a useful combination that broadens the
      scope of proteases for synthesis.
AB  - [reaction: see text] We present an irreversible and efficient protease-based
      method for peptide synthesis which occurs independently of the primary
      specificity of proteases and also without proteolytic side reactions. The key
      feature of this approach is the combination of the substrate mimetics strategy
      with frozen state enzymology. Model reactions catalyzed by several proteases
      qualify this approach as a powerful concept in the direction of a more universal
      application of proteases as biocatalysts for peptide ligation.

PMID- 10891222
TI  - A stereoselective synthesis of the C-10 to C-18 (right-half) fragment of
      mycalamides employing lewis acid promoted intermolecular aldol reaction.
AB  - [reaction: see text] Beginning with D-mannitol, a stereoselective synthesis of
      the right-half segment of the mycalamides has been accomplished by employing
      Lewis acid catalyzed intermolecular aldol reaction and oxypalladation as the key
      steps.

PMID- 10891223
TI  - Decomposition of 2-(1-hydroxybenzyl)thiamin. Ruling out stepwise cationic
      fragmentation.
AB  - [reaction: see text] The rapid fragmentation of 2-(1-hydroxybenzyl)thiamin (1) is
      initiated by transfer of a proton from C2alpha to give an enamine. The subsequent
      irreversible process can be written as a concerted (or stepwise) rearrangement
      involving migration of the hydroxyl hydrogen to the methylene bridge. An
      attractive alternative is internal addition of C2alpha to the pyrimidine,
      generating a carbocation. However, addition of azide to the reaction solution,
      which could trap the carbocation, has no effect on the rate or products of
      reaction.

PMID- 10891224
TI  - A second-generation synthesis of polypyrrolinone nonpeptidomimetics: prelude to
      the synthesis of polypyrrolinones on solid support.
AB  - [reaction: see text] A second-generation asymmetric synthesis of polypyrrolinones
      (3) has been achieved exploiting scalemic alpha-aminolactones (1) as building
      blocks. Imine formation between an appropriate lactone (1) and aldehyde (2),
      followed in turn by pyrrolinone ring construction promoted by KHMDS in the
      presence of 18-crown-6 and modified Swern oxidation furnished pyrrolinone
      aldehyde 3. This iterative, efficient three-step protocol paves the way for the
      synthesis of polypyrrolinones on solid support.

PMID- 10891225
TI  - Synthesis of polypyrrolinones on solid support.
AB  - [reaction: see text] An efficient, three-step iterative synthesis of
      polypyrrolinones has been achieved on solid support, setting the stage for the
      construction of a wide variety of libraries based on the pyrrolinone scaffold.
      Central to the approach is an effective end-game sequence featuring pyrrolinone
      ring construction with traceless release from the solid support.

PMID- 10891226
TI  - Aza-bis(oxazolines): new chiral ligands for asymmetric catalysis
AB  - Aza-bis(oxazolines) are introduced as chiral ligands for asymmetric catalysis
      combining the advantages of easy availability of bis(oxazolines) and backbone
      variability of aza-semicorrins. Especially, the title ligands could be attached
      to a polymeric support, which allowed the development of easily recoverable
      copper(I)-catalysts for asymmetric cyclopropanation reactions.

PMID- 10891227
TI  - One-pot stereoselective synthesis of tricyclic bislactones from 2-pyrones and 2
      methoxyfuran.
AB  - [reaction: see text] A one-pot synthesis of the title compounds via highly chemo
      , regio-, and stereoselective Diels-Alder reactions of 2-pyrones with 2
      methoxyfuran is described.

PMID- 10891228
TI  - Efficient cross-coupling reactions of aryl chlorides and bromides with phenyl- or
      vinyltrimethoxysilane mediated by a Palladium/Imidazolium chloride system
AB  - A combination of palladium acetate and the imidazolium salt IPr.HCl (1, IPr = 1,3
      bis(2,6-diisopropylphenyl)imidazol-2-ylidene) has proven to be highly efficient
      in the cross coupling reactions of aryl bromides and electron-deficient aryl
      chlorides with phenyltrimethoxysilane or vinyltrimethoxysilane. The catalytic
      performance of this system was found to be comparable to that of systems using
      PCy(3) and P(o-tol)(3).

PMID- 10891230
TI  - Preparation of 5-substituted 3-aminofuran-2-carboxylate esters.
AB  - [reaction: see text] An efficient method for the preparation of 3-aminofuran-2
      carboxylate esters has been developed. This method is based on the reaction of an
      alpha-cyanoketone with ethyl glyoxylate under Mitsunobu conditions to produce a
      vinyl ether in good yield. Subsequent treatment of the vinyl ether with sodium
      hydride afforded the 3-aminofuran. It was also found that a one-pot procedure
      using the Mitsunobu reaction followed by cyclization afforded the 3-aminofuran in
      comparable yield. Currently, this method is limited to the synthesis of 5-alkyl-,
      5-aryl-, and 4,5-fused bicyclic furans.

PMID- 10891229
TI  - General approach for the synthesis of sarpagine/ajmaline indole alkaloids.
      Stereospecific total synthesis of the sarpagine alkaloid (+)-vellosimine.
AB  - [reaction: see text] (+)-Vellosimine has been synthesized enantiospecifically in
      27% overall yield from commercially available D-(+)-tryptophan methyl ester via
      the asymmetric Pictet-Spengler reaction and a stereocontrolled intramolecular
      palladium-coupling reaction as key steps.

PMID- 10891231
TI  - Stereoselective synthesis of optically active beta-lactams, potential inhibitors
      of pilus assembly in pathogenic bacteria.
AB  - [reaction: see text] Optically active beta-lactams 3 are obtained in excellent
      yields (up to 93%) and with complete stereoselectivity from Meldrum's acid
      derivatives 1 and Delta(2)-thiazolines 2. A selective reduction to aldehydes 5 (R
      = Ar or CH(2)Ar) was then accomplished by using DIBAL-H. This rigid framework,
      with stereochemistry different than that of penicillin, is designed to be a
      suitable scaffold for the development of compounds inhibiting pilus formation in
      uropathogenic Escherichia coli.

PMID- 10891232
TI  - Radical stabilizing ability of the ferrocenyl and cyclobutadieneiron tricarbonyl
      groups
AB  - Computational studies indicate that ferrocenyl-substituted methyl radicals owe
      their stability to a spin delocalization mechanism involving Fe and a major
      contribution from an eta(4) form. Cyclobutadieneiron tricarbonyl substituted
      methyl radicals are also calculated to be highly stabilized by spin
      delocalization onto Fe and a major contribution from an eta(3) form.

PMID- 10891233
TI  - Stereoselective synthesis of (-)-acanthoic acid.
AB  - [reaction: see text] The first stereoselective synthesis of (-)-acanthoic acid
      (1) has been designed and accomplished. Our synthetic plan departs from (-)
      Wieland-Miesher ketone (7) and calls upon a Diels-Alder cycloaddition reaction
      for the construction of the C ring of 1. The described synthesis confirms the
      proposed stereochemistry of 1 and represents an efficient entry into an
      unexplored class of biologically active diterpenes.

PMID- 10891234
TI  - Scalar coupling across the hydrogen bond in 1,3- and 1,4-diols.
AB  - [reaction: see text] Scalar coupling between hydroxyl groups sharing a 1,4- or 1,
      3-intramolecular hydrogen bond can be readily detected using standard 2D NMR
      techniques. Analyses of isotopically perturbed 2D J-resolved spectra have
      revealed (h2)J to be on the order of 0.3 Hz in systems such as diols 2 and 3. A
      standard 2D COSY experiment, modified to detect small coupling constants, is
      shown to be a convenient method for detecting (h2)J in these systems. Couplings
      derived from density functional finite perturbation theory (DFT/FPT) are found to
      be in general agreement with experimental data.

PMID- 10891235
TI  - A cyclic oligophenylene containing two 1,8-naphthalene units bridged by two face
      to-face biphenyl linkages exhibiting unusual strain and pi-pi interaction
AB  - 1,8-[1,8-Naphthalenediylbis(4',4-biphenyldiyl)]naphthalene, a very stable
      strained cyclophane, has been synthesized in moderate yield using the copper
      catalyzed coupling of 1, 8-bis(4-(tributylstannyl)phenyl)naphthalene. The X-ray
      analysis of the titled compound discloses bent p,p'-biphenylylene chains with
      splayed naphthalene rings, and the p,p'-biphenylylene chains located face-to-face
      indicate a fairly strong pi-pi interaction.

PMID- 10891236
TI  - Synthesis of alpha-substituted allylic amines via a modified bruylants reaction
AB  - Silver tetrafluoroborate, used as an iminium ion promoter from alpha-amino
      nitriles, is an efficient additive in the Bruylants reaction involving vinylic
      Grignards. Improved yields of allylic amines were obtained when the starting
      alpha-amino nitrile was treated with this silver salt prior to its reaction with
      the vinylic Grignard. This improvement was not observed in the case of acetylenic
      Grignards. The reactivity of other vinyl organometallics (M = Zn, Li, Al, Cu, Si)
      was briefly examined.

PMID- 10891237
TI  - A synthesis of aromatic five- and six-membered B-N heterocycles via ring closing
      metathesis
AB  - The ring closing metathesis on appropriate vinyl or allyl aminoboranes (1 or 2)
      gives azaboracycloalkenes (3 or 4) which can be converted to azaborolides (5) or
      azaborines (6).

PMID- 10891238
TI  - Facile construction of novel polycyclic ring systems using a metallocarbenoid
      induced cyclization of acetylenic diazo carbonyl compounds
AB  - The Rh(II)-catalyzed reaction of diazo 2-propynyl maolonamic acid ester
      derivatives produce furo[3,4-c]furans in excellent yield. The methodology was
      applied to the synthesis of several polyheterocyclic systems by first generating
      a 2-alkoxy-substituted furan and then allowing it to undergo a subsequent
      intramolecular Diels-Alder cycloaddition. Ring opening of the resulting
      cycloadduct is followed by deprotonation to furnish a rearranged keto lactone.

PMID- 10891239
TI  - Dicobalt octacarbonyl-catalyzed tandem
AB  - Novel 5-5-6 tricyclic compounds containing cyclopentenone have been constructed
      by the dicobalt octacarbonyl catalyzed tandem [2 + 2 + 1] and [2 + 2 + 2]
      cycloaddition reaction between a diyne and two phenylacethylene under CO
      pressure.

PMID- 10891240
TI  - New stable reagents for the nucleophilic trifluoromethylation. 1.
      Trifluoromethylation Of carbonyl compounds with N-formylmorpholine derivatives
AB  - A new stable equivalent of the trifluoromethyl anion has been synthesized from
      fluoroform. It reacts with nonenolizable carbonyl compounds such as the Ruppert's
      reagent.

PMID- 10891241
TI  - Platinum-catalyzed diboration using a commercially available catalyst: diboration
      of aldimines to alpha-aminoboronate esters
AB  - Commercially available Pt(cod)Cl(2) catalyzes the diboration of alkenes, alkynes,
      and aldimines using bis(catecholato)diboron (cod = 1,5-cyclooctadiene). Catalyzed
      aldimine diboration provides the first direct route to alpha-aminoboronate
      esters. The diboration product from N-benzylidene-2,6-dimethylaniline is
      structurally characterized.

PMID- 10891242
TI  - Quinone approaches toward the synthesis of aflatoxin B(2).
AB  - [reaction: see text] Quinones bearing electron-withdrawing groups can serve as
      useful precursors to furobenzofuran ring systems through their reaction with 2,3
      dihydrofuran. Formal racemic and stereoselective syntheses of the fungal
      metabolite aflatoxin B(2) are described that utilize this approach to construct
      the tricyclic ABC-ring core of the molecule.

PMID- 10891243
TI  - Synthesis of allophanate-derived branched glycoforms from alcohols and p
      nitrophenyl carbamates.
AB  - [reaction: see text] The formation of saccharide-derived carbamates and alkyl 2,
      4-dialkylallophanates from alcohols and p-nitrophenyl carbamates is described.
      Optimization of allophanate formation has led to the synthesis of branched
      glycoforms with inter-saccharide allophanate linkages that are rigidified by
      intramolecular hydrogen bonds.

PMID- 10891244
TI  - The selective reaction of primary amines with carbonyl imidazole containing
      compounds: selective amide and carbamate synthesis
AB  - A new highly selective synthesis of amides and carbamates is described. In both
      cases the syntheses involve the formation of carbonyl imidazole intermediates
      which subsequently undergo previously unreported selective reactions with primary
      amines. Acid imidazolides with sufficient chain length will exclusively react
      with primary amines even in the presence of secondary and tertiary functionality.
      The imidazole carboxylic esters of secondary or tertiary alcohols also react
      selectively with primary amines, forming controlled carbamate structures.

PMID- 10891245
TI  - A concise synthesis of topsentin A and nortopsentins B and D.
AB  - [reaction: see text] A concise synthesis of topsentin A (R(1) = R(2) = H) and
      nortopsentins B (R(1) = Br, R(2) = H) and D (R(1) = R(2) = H) is described from
      oxotryptamine 5 via reduction of acyl cyanide 4. Regiospecific bromination of 3
      cyanoindole afforded 6-bromo-3-cyanoindole (10) as the major product.

PMID- 10891246
TI  - A general approach to cyathin diterpenes. Total synthesis of allocyathin B(3).
AB  - [reaction: see text] The synthesis of allocyathin B(3) from an advanced
      intermediate possessing the ring system and relative stereochemistry but lacking
      the isopropyl and hydroxymethyl groups is reported. The isopropyl group was
      introduced by radical cyclization of a methyl propargyl acetal of an alpha-bromo
      ketone, and the hydroxymethyl group was generated by Pd-catalyzed carbonylation
      of a vinyl triflate. The route provides functionalized intermediates that could
      allow access to more complex members of the cyathin family of diterpenes.

PMID- 10891247
TI  - o-(Bromomethyl)-substituted tetraarylporphyrin building blocks.
AB  - [structure: see text] A series of novel poly-o-(bromomethyl)ated
      tetraarylporphyrins was synthesized. Their usefulness as building blocks for
      porphyrinic materials is demonstrated.

PMID- 10891248
TI  - One-Pot synthesis of photochromic naphthopyrans in the solid state
AB  - p-TsOH-catalyzed condensation reactions of 1,1-diaryl-2-propyn-1-ol (1) and 2
      naphthol (2) in the solid state gave 3, 3-diaryl-3H-naphtho[2,1-b]pyran (6) via
      Claisen rearrangement. Similar reactions of 1 with 2,6- (7) and 2,7
      dihydroxynaphthalenes (8) afforded naphthodipyrane derivatives 9 and 10,
      respectively. Bis-naphthopyran derivatives 12 were also obtained by the reaction
      of 1,1,6,6-tetraaryl-2,5-hexadiyn-1,6-diol (11) and 2-naphthol (2) in the solid
      state.

PMID- 10891249
TI  - Synthesis of glycosyl-1-phosphates via dehydrative glycosylation.
AB  - [reaction: see text] Direct synthetic access to glycosyl-1-phosphates is
      accomplished with the dehydrative coupling of carbohydrate hemiacetals and
      dialkyl phosphates, employing dibenzothiophene-5-oxide and triflic anhydride. The
      procedure offers a new and versatile method for efficient preparation of a host
      of glycosyl-1-phosphates of variable structure with good control over anomeric
      selectivity.

PMID- 10891250
TI  - Cleavage of N ',N '-dialkylhydrazides with PhI(OH)OTs
AB  - N',N'-Dimethylhydrazides are efficiently cleaved to give the carboxylic acid upon
      treatment with PhI(OH)OTs in water or water/CH(2)Cl(2) mixtures. The reaction
      occurs with the evolution of a gas.

PMID- 10891251
TI  - A "traceless" Staudinger ligation for the chemoselective synthesis of amide
      bonds.
AB  - [reaction: see text] Here we report a novel modification of our previously
      reported "Staudinger ligation" that generates an amide bond from an azide and a
      specifically functionalized phosphine. This method for the selective formation of
      an amide bond, which does not require the orthogonal protection of distal
      functional groups, should find general utility in synthetic and biological
      chemistry.

PMID- 10891252
TI  - Stereoselectivity of macrocyclic ring-closing olefin metathesis.
AB  - [reaction: see text] Macrocyclic ring-closing olefin metathesis using ruthenium
      catalyst 3 was performed to produce a 14-membered lactone. The E/Z ratio of
      lactone was high regardless of the R group (auxiliary) or the initial alkene
      stereochemistry. A kinetic study demonstrates that the high E/Z ratio is due to
      secondary metathesis reactions that isomerize the product to the thermodynamic
      E/Z ratio.

PMID- 10891253
TI  - Asymmetric total synthesis of (-)-mycothiazole.
AB  - [structure: see text] In this Letter we describe the first total synthesis of
      mycothiazole, a polyketide thiazole from a marine sponge. Key steps include our
      CMD oxidation for the conversion of thiazolidine 11 to thiazole 12 and the Nagao
      acetate aldol reaction of 5 with aldehyde 4 to construct the chiral secondary
      alcohol. The skipped diene was constructed by the standard Stille coupling, and
      the conjugated diene was synthesized by lithium(I)- and copper(I)-mediated Stille
      coupling.

PMID- 10891254
TI  - Total synthesis of reveromycin A.
AB  - The stereoselective total synthesis of reveromycin A (1), a potent inhibitor of
      eukaryotic cell growth, has been accomplished on the basis of the
      stereocontrolled construction of the 6,6-spiroketal system, efficient
      succinylation of the tert-alcohol under high pressure, and the introduction of
      the unsaturated side chains.

PMID- 10891255
TI  - Underquaternized anion exchange resins as covalent scavengers
AB  - The use of partially quaternized, chloromethylated polystyrene as a covalent
      scavenger of cholate ion in aqueous media has been demonstrated. The ability of
      such polymers to scavenge organic anions by covalent as well as by ionic means
      has important implications in the areas of medicinal and environmental chemistry,
      which are briefly discussed.

PMID- 10891256
TI  - Umpolung of chiral 2-ethynylaziridines: Indium(I)-mediated stereoselective
      synthesis of nonracemic 1,3-amino alcohols bearing three chiral centers,
      catalyzed by palladium(0)
AB  - Treatment of 3-alkyl-2-ethynylaziridines with InI in the presence of
      Pd(PPh(3))(4) and H(2)O gave allenylindium reagents bearing a protected amino
      group in high yields. Stereoselective addition of the allenylindium to aldehydes
      affords 2-ethynyl-1,3-amino alcohols bearing three chiral centers in good yields.

PMID- 10891257
TI  - Diastereoselective alkylations of oxazolidinone glycolates: a useful extension of
      the Evans asymmetric alkylation.
AB  - [reaction: see text] The diastereoselective alkylation of glycolate
      oxazolidinones has been demonstrated as a method for the enantioselective
      preparation of alpha-alkoxy carboxylic acid derivatives and selectively protected
      1,2-diols. Various protecting groups on the glycolate hydroxyl and multiple
      substitution patterns on allylic iodides are tolerated in the alkylation. Yields
      for the alkylations are typically 70-85% with diastereoselectivities of >98:2.

PMID- 10891258
TI  - Radical cyclization of beta-aminoacrylates: synthesis of (-)-indolizidine 223AB.
AB  - [reaction: see text] (-)-Indolizidine 223AB was synthesized via radical
      cyclization of the beta-aminoacrylate derivative of a trans-2,5-disubstituted
      pyrrolidine. The trans-2,5-disubstituted pyrrolidine substrate was prepared by
      radical cyclization of a Ses-protected beta-aminoacrylate.

PMID- 10891259
TI  - Synthesis of beta-hydroxy ketones and vinylsilanes from homopropargylic alcohols
      by intramolecular hydrosilation
AB  - Catalytic intramolecular hydrosilation of nonracemic homopropargylic alcohols
      affords the corresponding five-membered cyclic siloxanes regiospecifically.
      Oxidation or alkylmetal addition converts these intermediates into beta-hydroxy
      ketones or vinylsilanes under mild conditions.

PMID- 10891260
TI  - Asymmetric wolff rearrangement reactions with alpha-alkylated-alpha-diazoketones:
      stereoselective synthesis of alpha-substituted-beta-amino acid derivatives
AB  - Photoinduced asymmetric Wolff rearrangement reactions were performed with alpha
      amino-alpha'-methyl-alpha'-diazoketones to afford alpha-methyl-beta-amino acid
      esters with good stereoselectivity. Factors that may influence the
      stereochemistry were examined, including steric effects and temperature
      dependence, which had a great impact on the stereochemistry.

PMID- 10891261
TI  - Early evolution of cytochrome bc complexes.
AB  - Primary structures, functional characteristics and phylogenetic relationships of
      subunits of cytochrome bc complexes from phylogenetically diverse bacterial and
      archaeal species were analysed. A single case of lateral gene transfer, i.e. the
      import of an epsilon-proteobacterial cytochrome bc(1) complex into Aquificales,
      was identified. For the enzyme in the remainder of the species studied, the
      obtained phylogenies were globally in line with small subunit rRNA trees. The
      distribution of a few key phylogenetic markers, such as contiguousness of
      cytochrome b, nature of the c-type subunit or spacing between b-heme ligands, are
      discussed. A localised modification of previous tree topologies is proposed on
      the basis of the obtained data. The comparison of extant enzymes furthermore
      allowed us to define the minimal functional and evolutionary core of the enzyme.
      The data furthermore suggest that the ancestral enzyme was put together from
      subunits that previously had played a role in other electron transfer chains.

PMID- 10891262
TI  - Use of a new label, (13)==(18)O, in the determination of a structural model of
      phospholamban in a lipid bilayer. Spatial restraints resolve the ambiguity
      arising from interpretations of mutagenesis data.
AB  - A structural model of pentameric phospholamban (Plb) in a lipid bilayer has been
      derived using a combination of experimental data, obtained from ATR-FTIR site
      directed dichroism, and the implementation of the resulting restraints during a
      molecular dynamics simulation. Plb (residues 24-52) has been synthesised
      incorporating a new label, 1-(13)C==(18)O, at residues 42 and 43. We have not
      only determined the tilt of the helices, 10(+/-6) degrees, but also the relative
      orientation of the transmembrane segments, with an omega angle of -32(+/-10)
      degrees for L42. This angle is taken as zero in the direction of the helix tilt.
      Plb is a simple test case where site-directed dichroism has been applied to
      resolve the indeterminacy arising from the mutagenesis data available. The
      results presented point specifically to a single structural model for Plb.

PMID- 10891263
TI  - Extended sugar slide function for the periplasmic coiled coil domain of ScrY.
AB  - Several bacterial outer membrane proteins have a periplasmic extension whose
      structure and function remain elusive. Here, the structure/function relationship
      of the N-terminal periplasmic domain of the sucrose-specific outer membrane
      channel ScrY was investigated. Circular dichroism and analytical centrifugation
      demonstrated that the N-terminal domain formed a parallel, three-stranded coiled
      coil. When this domain was fused to the maltose-specific channel LamB, permeation
      of maltooligosaccharides in liposomes increased with increasing sugar chain
      length whereas wild-type LamB showed the opposite effect. Current fluctuation
      analysis demonstrated increased off-rates for sugar transport through the fusion
      protein. Moreover, equilibrium dialysis showed an affinity of sucrose for the
      isolated N-terminal peptide. Together these results demonstrate a novel function
      for coiled coil domains, operating as an extended sugar slide.

PMID- 10891264
TI  - Structures of type 2 peroxisomal targeting signals in two trypanosomatid
      aldolases.
AB  - Trypanosomatids, unicellular organisms responsible for several global diseases,
      contain unique organelles called glycosomes in which the first seven glycolytic
      enzymes are sequestered. We report the crystal structures of glycosomal fructose
      1,6-bisphosphate aldolase from two major tropical pathogens, Trypanosoma brucei
      and Leishmania mexicana, the causative agents of African sleeping sickness and
      one form of leishmaniasis, respectively. Unlike mammalian aldolases, the T.
      brucei and L. mexicana aldolases contain nonameric N-terminal type 2 peroxisomal
      targeting signals (PTS2s) to direct their import into the glycosome. In both
      tetrameric trypanosomatid aldolases, the PTS2s from two different subunits form
      two closely intertwined structures. These "PTS2 dimers", which have very similar
      conformations in the two aldolase structures, are the first reported
      conformations of a glycosomal or peroxisomal PTS2, and provide opportunities for
      the design of trypanocidal compounds.

PMID- 10891265
TI  - The effect of the DNA conformation on the rate of NtrC activated transcription of
      Escherichia coli RNA polymerase.sigma(54) holoenzyme.
AB  - The transcription activator protein NtrC (nitrogen regulatory protein C) can
      catalyze the transition of Escherichia coli RNA polymerase complexed with the
      sigma 54 factor (RNAP.sigma(54)) from the closed complex (RNAP.sigma(54) bound at
      the promoter) to the open complex (melting of the promoter DNA). This process
      involves phosphorylation of NtrC (NtrC-P), assembly of an octameric NtrC-P
      complex at the enhancer sequence, interaction of this complex with promoter-bound
      RNAP.sigma(54) via DNA looping, and hydrolysis of ATP. We have used this system
      to study the influence of the DNA conformation on the transcription activation
      rate in single-round transcription experiments with superhelical plasmids as well
      as linearized templates. Most of the templates had an intrinsically curved DNA
      sequence between the enhancer and the promoter and differed with respect to the
      location of the curvature and the distance between the two DNA sites. The
      following results were obtained: (i) a ten- to 60-fold higher activation rate was
      observed with the superhelical templates as compared to the linearized
      conformation; (ii) the presence of an intrinsically curved DNA sequence increased
      the activation rate of linear templates about five times; (iii) no systematic
      effect for the presence and/or location of the inserted curved sequence was
      observed for the superhelical templates. However, the transcription activation
      rate varied up to a factor of 10 between some of the constructs. (iv) Differences
      in the distance between enhancer and promoter had little effect for the
      superhelical templates studied. The results were compared with theoretical
      calculations for the dependence of the contact probability between enhancer and
      promoter expressed as the molar local concentration j(M). A correlation of j(M)
      with the transcription activation rate was observed for values of 10(-8)
      M<j(M)<10(-6) M and a kinetic model for NtrC-P-catalyzed open complex formation
      was developed.

PMID- 10891266
TI  - Four genes encode acetylcholinesterases in the nematodes Caenorhabditis elegans
      and Caenorhabditis briggsae. cDNA sequences, genomic structures, mutations and in
      vivo expression.
AB  - We report the full coding sequences and the genomic organization of the four
      genes encoding acetylcholinesterase (AChE) in Caenorhabditis elegans and
      Caenorhabditis briggsae, in relation to the properties of the encoded enzymes.
      ace-1 and ace-2, located on chromosome X and I, respectively, encode two AChEs
      (ACE-1 and ACE-2) that present 35% identity. The C-terminal end of ACE-1 is
      homologous to the C terminus of T subunits of vertebrate AChEs. ACE-1
      oligomerizes into amphiphilic tetramers. ACE-2 has a hydrophobic C terminus of H
      type. It associates into glycolipid-anchored dimers. In C. elegans and C.
      briggsae, ace-3 and ace-4 are organized in tandem on chromosome II, with only 356
      nt and 369 nt, respectively, between the stop codon of ace-4 (upstream gene) and
      the ATG of ace-3. ace-3 produces only 5 % of the total AChE activity. It encodes
      an H subunit that associates into dimers of glycolipid-anchored catalytic
      subunits, which are highly resistant to the usual AChE inhibitors, and which
      hydrolyze butyrylthiocholine faster than acetylthiocholine. ACE-4 is closer to
      ACE-3 (54 % identity) than to ACE-1 or ACE-2. The usual sequence FGESAG
      surrounding the active serine residue in cholinesterases is changed to FGQSAG in
      ace-4. ACE-4 was not detected by our current biochemical methods, although the
      gene is transcribed in vivo. However the level of ace-4 mRNAs is far lower than
      those of ace-1, ace-2 and ace-3. The ace-2, ace-3 and ace-4 transcripts were
      found to be trans-spliced by both SL1 and SL2, although these genes are not
      included in typical operons. The molecular bases of null mutations g72 (ace-2),
      p1304 and dc2 (ace-3) have been identified.

PMID- 10891267
TI  - Comparative genetic and physiological studies of the MAP kinase Mpk1p from
      Kluyveromyces lactis and Saccharomyces cerevisiae.
AB  - MAP kinases are essential components of signal transduction pathways in yeasts
      and higher eukaryotes. Here, we report on the isolation of the gene encoding the
      MAP kinase KlMpk1p by complementation of the respective Saccharomyces cerevisiae
      deletion mutant with a genomic library from Kluyveromyces lactis. Sequencing
      revealed the presence of an open reading frame capable of encoding a protein of
      520 amino acid residues with a deduced molecular mass of 59.726 Da. The deduced
      protein sequence displayed a high degree of similarity to known MAP kinases from
      yeast to man, with an overall identity of 70 % to ScMpk1p. One-hybrid analysis
      demonstrated the presence of a cryptic transcriptional activation domain in the C
      terminal part of the protein. Deletion of this sequence in ScMpk1p resulted in a
      reduced MAP kinase activity (measured by an indirect assay), an increased
      sensitivity towards caffeine and an increased resistance against Calcofluor
      white. Complete deletion mutants of Klmpk1 display an osmo-remedial phenotype on
      rich medium, but are capable of growth in the absence of osmotic stabilization on
      synthetic medium. As Scmpk1 deletion mutants, they are sensitive to cell surface
      destabilizing agents such as Calcofluor white and SDS, and growth is inhibited in
      the presence of 5 mM caffeine. Overexpression of KlMPK1 did not produce a growth
      defect in S. cerevisiae or in K. lactis.

PMID- 10891268
TI  - Surface tongue-and-groove contours on lens MIP facilitate cell-to-cell adherence.
AB  - The lens major intrinsic protein (MIP, AQP0) is known to function as a water and
      solute channel. However, MIP has also been reported to occur in close membrane
      contacts between lens fiber cells, indicating that it has adhesive properties in
      addition to its channel function. Using atomic force and cryo-electron microscopy
      we document that crystalline sheets reconstituted from purified ovine lens MIP
      mostly consisted of two layers. MIP lattices in the apposing membranes were in
      precise register, and determination of the membrane sidedness demonstrated that
      MIP molecules bound to each other via their extracellular surfaces. The surface
      structure of the latter was resolved to 0.61 nm and revealed two protruding
      domains providing a tight "tongue-and-groove" fit between apposing MIP molecules.
      Cryo-electron crystallography produced a projection map at 0.69 nm resolution
      with a mirror symmetry axis at 45 degrees to the lattice which was consistent
      with the double-layered nature of the reconstituted sheets. These data strongly
      suggest an adhesive function of MIP, and strengthen the view that MIP serves dual
      roles in the lens.

PMID- 10891269
TI  - Predicting U-turns in ribosomal RNA with comparative sequence analysis.
AB  - The U-turn is a well-known RNA motif characterized by a sharp reversal of the RNA
      backbone following a single-stranded uridine base. In experimentally determined U
      turn motifs, the nucleotides 3' to the turn are frequently involved in tertiary
      interactions, rendering this motif particularly attractive in RNA modeling and
      functional studies. The U-turn signature is composed of an UNR sequence pattern
      flanked by a Y:Y, Y:A (Y=pyrimidine) or G:A base juxtaposition. We have
      identified 33 potential UNR-type U-turns and 25 related GNRA-type U-turns in a
      large set of aligned 16 S and 23 S rRNA sequences. U-turn candidates occur in
      hairpin loops (34 times) as well as in internal and multi-stem loops (24 times).
      These are classified into ten families based on loop type, sequence pattern (UNR
      or GNRA) and the nature of the closing base juxtaposition. In 13 cases, the bases
      on the 3' side of the turn, or on the immediate 5' side, are involved in tertiary
      covariations, making these sites strong candidates for tertiary interactions.

PMID- 10891270
TI  - Solution structure of the cysteine-rich domain of the Escherichia coli chaperone
      protein DnaJ.
AB  - The solution structure of the cysteine-rich (CR) domain of Escherichia coli DnaJ
      has been solved by NMR methods. The structure of a 79 residue CR domain construct
      shows a novel fold with an overall V-shaped extended beta-hairpin topology. The
      CR domain is characterized by four C-X-X-C-X-G-X-G sequence motifs that bind two
      zinc ions. Residues in these two zinc modules show strong similarities in the
      grouping of resonances in the (15)N-(1)H HSQC spectrum and display pseudo
      symmetry of the motifs in the calculated structures. The conformation of the
      cysteine residues coordinated to the zinc ion resembles that of the rubredoxin
      knuckle, but there are significant differences in hydrogen bonding patterns in
      the two motifs. Zinc (15)N-(1)H HSQC titrations indicate that the fold of the
      isolated DnaJ CR domain is zinc-dependent and that one zinc module folds before
      the other. The C-X-X-C-X-G-X-G sequence motif is highly conserved in CR domains
      from a wide variety of species. The three-dimensional structure of the E. coli CR
      domain indicates that this sequence conservation is likely to result in a
      conserved structural motif.

PMID- 10891271
TI  - A-form conformational motifs in ligand-bound DNA structures.
AB  - Recognition and biochemical processing of DNA requires that proteins and other
      ligands are able to distinguish their DNA binding sites from other parts of the
      molecule. In addition to the direct recognition elements embedded in the linear
      sequence of bases (i.e. hydrogen bonding sites), these molecular agents seemingly
      sense and/or induce an "indirect" conformational response in the DNA base-pairs
      that facilitates close intermolecular fitting. As part of an effort to decipher
      this sequence-dependent structural code, we have analyzed the extent of B-->A
      conformational conversion at individual base-pair steps in protein and drug-bound
      DNA crystal complexes. We take advantage of a novel structural parameter, the
      position of the phosphorus atom in the dimer reference frame, as well as other
      documented measures of local helical structure, e.g. torsion angles, base-pair
      step parameters. Our analysis pinpoints ligand-induced conformational changes
      that are difficult to detect from the global perspective used in other studies of
      DNA structure. The collective data provide new structural details on the
      conformational pathway connecting A and B-form DNA and illustrate how both
      proteins and drugs take advantage of the intrinsic conformational mechanics of
      the double helix. Significantly, the base-pair steps which exhibit pure A-DNA
      conformations in the crystal complexes follow the scale of A-forming tendencies
      exhibited by synthetic oligonucleotides in solution and the known polymorphism of
      synthetic DNA fibers. Moreover, most crystallographic examples of complete B-to-A
      deformations occur in complexes of DNA with enzymes that perform cutting or
      sealing operations at the (O3'-P) phosphodiester linkage. The B-->A
      transformation selectively exposes sugar-phosphate atoms, such as the 3'-oxygen
      atom, ordinarily buried within the chain backbone for enzymatic attack. The
      forced remodeling of DNA to the A-form also provides a mechanism for smoothly
      bending the double helix, for controlling the widths of the major and minor
      grooves, and for accessing the minor groove edges of individual base-pairs.

PMID- 10891272
TI  - Major groove recognition by three-stranded beta-sheets: affinity determinants and
      conserved structural features.
AB  - We present the results of a rational mutagenesis and binding-affinity study of
      the three-stranded beta-sheet-DNA interface in the complex formed by the amino
      terminal DNA-binding domain of the Tn916 integrase protein and its cognate
      binding site. The relative importance of interfacial contacts present in its NMR
      derived solution structure have been tested through mutagenesis, fluorescence
      anisotropy, and intrinsic quenching DNA-binding assays. We find that seven
      protein-DNA hydrogen bonds (two base-specific and five to phosphate groups)
      significantly contribute to the level of affinity. These interactions span the
      entire DNA-binding surface on the protein, but primarily originate from residues
      in only two strands of the sheet and loop L2. Interestingly, we show that highly
      populated, precisely defined intermolecular hydrogen bonds in the ensemble of
      conformers are invariably important for DNA-binding, implying that NMR-derived
      solution structures provide direct insight into the energetics of recognition.
      Unusual three-stranded beta-sheet-DNA interfaces have recently been discovered in
      three unrelated protein-DNA complexes. A comparative analysis of these structures
      reveals similar sheet positioning, the presence of two invariant interfacial
      contacts to the phosphodiester backbone, and two semi-conserved base-specific
      hydrogen bonds. Two of these conserved contacts significantly contribute to the
      affinity of the integrase-DNA complex, suggesting that the three-stranded beta
      sheet DNA-binding motif exhibits conserved principles of recognition.

PMID- 10891273
TI  - A model for the PI-SceIxDNA complex based on multiple base and phosphate backbone
      specific photocross-links.
AB  - We have synthesized different oligodeoxynucleotides carrying, in single positions
      of the >36 bp recognition site of PI-SceI, photoreactive base analogues (5
      iododeoxypyrimidines) or phosphate modifications (p
      azidophenacylphosphorothioates) and used them in photocross-linking experiments
      with PI-SceI to probe the protein-DNA interface of the specific complex between
      the homing endonuclease PI-SceI and its DNA substrate. One base-specific and
      several backbone-specific cross-links were analyzed in detail: the cross-linking
      positions were identified by Edman degradation of isolated cross-linked
      peptidexoligodeoxynucleotide adducts and confirmed by site-directed mutagenesis.
      Based on these results and the crystal structure of PI-SceI, a model for the
      structure of the PI-SceIxDNA complex is proposed.

PMID- 10891274
TI  - Crystal structure of the carbohydrate recognition domain of the H1 subunit of the
      asialoglycoprotein receptor.
AB  - The human asialoglycoprotein receptor (ASGPR), also called hepatic lectin, is an
      integral membrane protein and is responsible for the clearance of desialylated,
      galactose-terminal glycoproteins from the circulation by receptor-mediated
      endocytosis. It can be subdivided into four functional domains: the cytosolic
      domain, the transmembrane domain, the stalk and the carbohydrate recognition
      domain (CRD). The galactose-binding domains belong to the superfamily of C-type
      (calcium-dependent) lectins, in particular to the long-form subfamily with three
      conserved intramolecular disulphide bonds. It is able to bind terminal non
      reducing galactose residues and N-acetyl-galactosamine residues of desialated tri
      or tetra-antennary N-linked glycans. The ASGPR is a potential liver-specific
      receptor for hepatitis B virus and Marburg virus and has been used to target
      exogenous molecules specifically to hepatocytes for diagnostic and therapeutic
      purposes.Here, we present the X-ray crystal structure of the carbohydrate
      recognition domain of the major subunit H1 at 2.3 A resolution. While the overall
      fold of this and other known C-type lectin structures are well conserved, the
      positions of the bound calcium ions are not, indicating that the fold is
      stabilised by alternative mechanisms in different branches of the C-type lectin
      family. It is the first CRD structure where three calcium ions form an intergral
      part of the structure. In addition, the structure provides direct confirmation
      for the conversion of the ligand-binding site of the mannose-binding protein to
      an asialoglycoprotein receptor-like specificity suggested by Drickamer and
      colleagues. In agreement with the prediction that the coiled-coil domain of the
      ASGPR is separated from the CRD and its N-terminal disulphide bridge by several
      residues, these residues are indeed not alpha-helical, while in tetranectin they
      form an alpha-helical coiled-coil.

PMID- 10891275
TI  - Conformational changes and cleavage by the homing endonuclease I-PpoI: a critical
      role for a leucine residue in the active site.
AB  - The homing endonuclease I-PpoI severely bends its DNA target, resulting in
      significant deformations of the minor and major groove near the scissile
      phosphate groups. To study the role of conformational changes within the protein
      catalyst and the DNA substrate, we have determined the structure of the enzyme in
      the absence of bound DNA, performed gel retardation analyses of DNA binding and
      bending, and have mutagenized a leucine residue that contacts an adenine
      nucleotide at the site of cleavage. The structure of the L116A/DNA complex has
      been determined and the effects of the mutation on affinity and catalysis have
      been measured. The wild-type protein displays a rigid-body rotation of its
      individual subunits upon DNA binding. Homing site DNA is not detectably bent in
      the absence of protein, but is sharply bent in both the wild-type and L116A
      complexes. These results indicate that binding involves a large distortion of the
      DNA and a smaller change in protein conformation. Leucine 116 is critical for
      binding and catalysis: it appears to be important for forming a well-ordered
      protein-DNA complex at the cleavage site, for maximal deformation of the DNA, and
      for desolvation of the nucleotide bases that are partially unstacked in the
      enzyme complex.

PMID- 10891276
TI  - Crystal structure of an archaeal intein-encoded homing endonuclease PI-PfuI.
AB  - Inteins possess two different enzymatic activities, self-catalyzed protein
      splicing and site-specific DNA cleavage. These endonucleases, which are
      classified as part of the homing endonuclease family, initiate the mobility of
      their genetic elements into homologous alleles. They recognize long asymmetric
      nucleotide sequences and cleave both DNA strands in a monomer form. We present
      here the 2.1 A crystal structure of the archaeal PI-PfuI intein from Pyroccocus
      furiosus. The structure reveals a unique domain, designated here as the Stirrup
      domain, which is inserted between the Hint domain and an endonuclease domain. The
      horseshoe-shaped Hint domain contains a catalytic center for protein splicing,
      which involves both N and C-terminal residues. The endonuclease domain, which is
      inserted into the Hint domain, consists of two copies of substructure related by
      an internal pseudo 2-fold axis. In contrast with the I-CreI homing endonuclease,
      PI-PfuI possibly has two asymmetric catalytic sites at the center of a putative
      DNA-binding cleft formed by a pair of four-stranded beta-sheets. DNase I
      footprinting experiments showed that PI-PfuI covers more than 30 bp of the
      substrate asymmetrically across the cleavage site. A docking model of the DNA
      enzyme complex suggests that the endonuclease domain covers the 20 bp DNA duplex
      encompassing the cleavage site, whereas the Stirrup domain could make an
      additional contact with another upstream 10 bp region. For the double-strand
      break, the two strands in the DNA duplex were cleaved by PI-PfuI with different
      efficiencies. We suggest that the cleavage of each strand is catalyzed by each of
      the two non-equivalent active sites.

PMID- 10891277
TI  - The structure of reduced tryparedoxin peroxidase reveals a decamer and insight
      into reactivity of 2Cys-peroxiredoxins.
AB  - Tryparedoxin peroxidase (TryP) is a recently discovered 2Cys-peroxiredoxin
      involved in defence against oxidative stress in parasitic trypanosomatids. The
      crystal structure of recombinant Crithidia fasciculata TryP, in the reduced
      state, has been determined using multi-wavelength anomalous dispersion methods
      applied to a selenomethionyl derivative. The model comprises a decamer with 52
      symmetry, ten chloride ions with 23 water molecules and has been refined, using
      data to 3.2 A resolution (1 A=0.1 nm), to an R-factor and R(free) of 27.3 and
      28.6 %, respectively. Secondary structure topology places TryP along with
      tryparedoxin and glutathione peroxidase in a distinct subgroup of the thioredoxin
      super-family. The molecular details at the active site support ideas about the
      enzyme mechanism and comparisons with an oxidised 2Cys-peroxiredoxin reveal
      structural alterations induced by the change in oxidation state. These include a
      difference in quaternary structure from dimer (oxidised form) to decamer (reduced
      form). The 2Cys-peroxiredoxin assembly may prevent indiscriminate
      oligomerisation, localise ten peroxidase active sites and contribute to both the
      specificity of reduction by the redox partner tryparedoxin and attraction of
      peroxides into the active site.

PMID- 10891278
TI  - The structure of rhamnose isomerase from Escherichia coli and its relation with
      xylose isomerase illustrates a change between inter and intra-subunit
      complementation during evolution.
AB  - Using a new expression construct, rhamnose isomerase from Escherichia coli was
      purified and crystallized. The crystal structure was solved by multiple
      isomorphous replacement and refined to a crystallographic residual of 17.4 % at
      1.6 A resolution. Rhamnose isomerase is a tight tetramer of four (beta/alpha)(8)
      barrels. A comparison with other known structures reveals that rhamnose isomerase
      is most similar to xylose isomerase. Alignment of the sequences of the two
      enzymes based on their structures reveals a hitherto undetected sequence identity
      of 13 %, suggesting that the two enzymes evolved from a common precursor. The
      structure and arrangement of the (beta/alpha)(8)-barrels of rhamnose isomerase
      are very similar to xylose isomerase. Each enzyme does, however, have additional
      alpha-helical domains, which are involved in tetramer association, and largely
      differ in structure. The structures of complexes of rhamnose isomerase with the
      inhibitor l-rhamnitol and the natural substrate l-rhamnose were determined and
      suggest that an extended loop, which is disordered in the native enzyme, becomes
      ordered on substrate binding, and may exclude bulk solvent during catalysis.
      Unlike xylose isomerase, this loop does not extend across a subunit interface but
      contributes to the active site of its own subunit. It illustrates how an
      interconversion between inter and intra-subunit complementation can occur during
      evolution. In the crystal structure (although not necessarily in vivo) rhamnose
      isomerase appears to bind Zn(2+) at a "structural" site. In the presence of
      substrate the enzyme also binds Mn(2+) at a nearby "catalytic" site. An array of
      hydrophobic residues, not present in xylose isomerase, is likely to be
      responsible for the recognition of l-rhamnose as a substrate. The available
      structural data suggest that a metal-mediated hydride-shift mechanism, which is
      generally favored for xylose isomerase, is also feasible for rhamnose isomerase.

PMID- 10891279
TI  - Structure of coenzyme F(420) dependent methylenetetrahydromethanopterin reductase
      from two methanogenic archaea.
AB  - Coenzyme F(420)-dependent methylenetetrahydromethanopterin reductase (Mer) is an
      enzyme of the Cl metabolism in methanogenic and sulfate reducing archaea. It is
      composed of identical 35-40 kDa subunits and lacks a prosthetic group. The
      crystal structure of Mer from Methanopyrus kandleri (kMer) revealed in one
      crystal form a dimeric and in another a tetrameric oligomerisation state and that
      from Methanobacterium thermoautotrophicum (tMer) a dimeric state. Each monomer is
      primarily composed of a TIM-barrel fold enlarged by three insertion regions.
      Insertion regions 1 and 2 contribute to intersubunit interactions. Insertion
      regions 2 and 3 together with the C-terminal end of the TIM-barrel core form a
      cleft where the binding sites of coenzyme F(420) and methylene
      tetrahydromethanopterin are postulated. Close to the coenzyme F(420)-binding site
      lies a rarely observed non-prolyl cis-peptide bond. It is surprising that Mer is
      structurally most similar to a bacterial FMN-dependent luciferase which contains
      a non-prolyl cis-peptide bond at the equivalent position. The structure of Mer is
      also related to that of NADP-dependent FAD-harbouring methylenetetrahydrofolate
      reductase (MetF). However, Mer and MetF do not show sequence similarities
      although they bind related substrates and catalyze an analogous reaction.

PMID- 10891280
TI  - Role of domains 4 and 5 in elongation factor G functions on the ribosome.
AB  - Elongation factor G (EF-G) is a large, five domain GTPase that catalyses the
      translocation of the tRNAs on the bacterial ribosome at the expense of GTP. In
      the crystal structure of GDP-bound EF-G, domain 1 (G domain) makes direct
      contacts with domains 2 and 5, whereas domain 4 protrudes from the body of the
      molecule. Here, we show that the presence of both domains 4 and 5 is essential
      for tRNA translocation and for the turnover of the factor on the ribosome, but
      not for rapid single-round GTP hydrolysis by EF-G. Replacement of a highly
      conserved histidine residue at the tip of domain 4, His583, with lysine or
      arginine decreases the rate of tRNA translocation at least 100-fold, whereas the
      binding of the factor to the ribosome, GTP hydrolysis and P(i) release are not
      affected by the mutations. Various small deletions in the tip region of domain 4
      decrease the translocation activity of EF-G even further, but do not block the
      turnover of the factor. Unlike native EF-G, the mutants of EF-G lacking domains
      4/5 do not interact with the alpha-sarcin stem-loop of 23 S rRNA. These mutants
      are not released from the ribosome after GTP hydrolysis or translocation,
      indicating that the contact with, or a conformational change of, the alpha-sarcin
      stem-loop is required for EF-G release from the ribosome.

PMID- 10891281
TI  - Molecular dynamics simulations highlight mobile regions in proteins: A novel
      suggestion for converting a murine V(H) domain into a more tractable species.
AB  - The V(H) region of the murine antibody 1F7 has been identified as a single-domain
      chorismate mutase, but a tendency to denature and aggregate has hampered its
      biochemical characterization. Standard mutagenesis approaches targeting antibody
      chain dimerization areas have been exhausted. We describe a new approach to the
      problem, where we use molecular dynamics (MD) simulations to find the differences
      between the untractable protein and the known soluble V(H) domain from a llama
      antibody. MD simulations of proteins yield information on the relative stability
      and fluctuations of parts of the proteins. By comparing simulation results of two
      related proteins their differences in stability and fluctuations can be analyzed
      and may suggest mutations aimed at (de)stabilization of one of the two proteins.
      For the mouse versus llama simulations, this approach highlights an untried area
      in the protein which shows increased fluctuations. The replacement of this eight
      residue segment with the corresponding llama sequence gave a chimeric mutant
      which shows significantly decreased fluctuations. We see this as a general scheme
      to generate suggestions for mutagenesis experiments, not only obviously
      generalizable to other immunoglobulin domains, but to other protein systems as
      well.

PMID- 10891282
TI  - What can disulfide bonds tell us about protein energetics, function and folding:
      simulations and bioninformatics analysis.
AB  - We study the impact of disulfide bonds on protein stability and folding. Using
      lattice model simulations, we show that formation of a disulfide bond stabilizes
      a protein to an extent that depends on the distance along the chain between
      linked cysteine residues. However, the impact of disulfide bonds on folding
      kinetics varies broadly, from acceleration when disulfides are introduced in or
      close to the folding nucleus, to slowing when disulfides are introduced outside
      the nucleus. Having established the effect of disulfide bonds on stability, we
      study the correlation between the number of disulfide bonds and the composition
      of certain amino acid classes with the goal to use it as a statistical probe into
      factors that contribute to stability of proteins. We find that the number of
      disulfides is negatively correlated with aliphatic hydrophobic but not aromatic
      content. It is surprising that we observe a strong correlation of disulfide
      content with polar (Q,S,T,N) amino acid content and a strong negative correlation
      with charged (E,D,K,R) content. These findings provide insights into factors that
      determine protein stability and principles of protein design as well as possible
      relations of disulfide bonds and protein function.

PMID- 10891283
TI  - The fold of human aquaporin 1.
AB  - The fold of human aquaporin 1 is determined from cryo-electron microscopic data
      at 4.5 A resolution. The monomeric structure consists of two transmembrane triple
      helices arranged around a pseudo-2-fold axis connected by a long flexible
      extracellular loop. Each triplet contains between its second and third helix a
      functional loop containing the highly conserved fingerprint NPA motif. These
      functional loops are assumed to fold inwards between the two triplets, thereby
      forming the heart of the water channel. The helix topology was determined from
      the directionality pattern of each of the six transmembrane helices with respect
      to the membrane, together with constraints defined by the sequence and atomic
      force microscopy data. The directionality of the helices was determined by
      collecting the best-fitting orientations resulting from a search through the
      three-dimensional experimental map for a large number of alpha-helical fragments.
      Tests on cryo-electron crystallographic bacteriorhodopsin data suggest that our
      method is generally applicable to determine the topology of helical proteins for
      which only medium-resolution electron microscopy data are available.

PMID- 10891284
TI  - Catalysis of the oxidative folding of bovine pancreatic ribonuclease A by protein
      disulfide isomerase.
AB  - The major oxidative folding pathways of bovine pancreatic ribonuclease A at pH
      8.0 and 25 degrees C involve a pre-equilibrium steady state among ensembles of
      intermediates with zero, one, two, three and four disulfide bonds. The rate
      determining steps are the reshuffling of the unstructured three-disulfide
      ensemble to two native-like three-disulfide species, des-[65-72] and des-[40-95],
      that convert to the native structure during oxidative formation of the fourth
      disulfide bond. Under the same regeneration conditions, with oxidized and reduced
      DTT, used previously for kinetic oxidative-folding studies of this protein, the
      addition of 4 microM protein disulfide isomerase (PDI) was found to lead to
      catalysis of each disulfide-formation step, including the rate-limiting
      rearrangement steps in which the native-like intermediates des-[65-72] and des
      [40-95] are formed. The changes in the distribution of intermediates were also
      determined in the presence and absence of PDI at three different temperatures
      (with the DTT redox system) as well as at 25 degrees C (with the glutathione
      redox system). The results indicate that the acceleration of the formation of
      native protein by PDI, which we observed earlier, is due to PDI catalysis of each
      of the intermediate steps without changing the overall pathways or folding
      mechanism.

PMID- 10891285
TI  - Predicting subcellular localization of proteins based on their N-terminal amino
      acid sequence.
AB  - A neural network-based tool, TargetP, for large-scale subcellular location
      prediction of newly identified proteins has been developed. Using N-terminal
      sequence information only, it discriminates between proteins destined for the
      mitochondrion, the chloroplast, the secretory pathway, and "other" localizations
      with a success rate of 85% (plant) or 90% (non-plant) on redundancy-reduced test
      sets. From a TargetP analysis of the recently sequenced Arabidopsis thaliana
      chromosomes 2 and 4 and the Ensembl Homo sapiens protein set, we estimate that
      10% of all plant proteins are mitochondrial and 14% chloroplastic, and that the
      abundance of secretory proteins, in both Arabidopsis and Homo, is around 10%.
      TargetP also predicts cleavage sites with levels of correctly predicted sites
      ranging from approximately 40% to 50% (chloroplastic and mitochondrial
      presequences) to above 70% (secretory signal peptides). TargetP is available as a
      web-server at http://www.cbs.dtu.dk/services/TargetP/.

PMID- 10891287
TI  - Regulatory role of Th-2 cytokines, IL-10 and IL-4, in cardiac allograft
      rejection.
AB  - The host response to alloantigen results in T- and B-cell activation,
      upregulation of Class II MHC antigens, and cytokine production by Th-1 cells,
      resulting in generation of IL-2 and IFN gamma. Th-2 cell responses produce IL-4
      and IL-10 which may shift the immune response from the Th-1 pathway to Th-2
      responses, favoring Ig production. This could imply that Th-2-related cytokines
      protect allografts. In the following studies, employing cardiac heterotopic
      allografts in rats (Brown Norway into Lewis), we investigated regulatory roles of
      Th-2-related cytokines IL-4 and IL-10. Two strategies were used in animals
      receiving allografts: antibody-induced blocking of endogenous IL-4 or IL-10 and
      exogenous administration of either interleukin. Antibody to IL-4 failed to alter
      the rejection time, whereas anti-IL-10 greatly accelerated the rejection process.
      Northern blot analysis of RNA from allografted hearts revealed mRNA for both IL-4
      and IL-10, while immunostaining showed strong staining for IL-10 and very weak
      staining for IL-4. Exogenous administration of either IL-4 or 10 caused
      prolongation of allograft rejection times. These findings suggest that in rat
      cardiac allografts intrinsic IL-10 functions to attenuate the rejection process.

PMID- 10891286
TI  - Drosophila stretchin-MLCK is a novel member of the Titin/Myosin light chain
      kinase family.
AB  - Members of the titin/myosin light chain kinase family play an essential role in
      the organization of the actin/myosin cytoskeleton, especially in sarcomere
      assembly and function. In Drosophila melanogaster, projectin is so far the only
      member of this family for which a transcription unit has been characterized. The
      locus of another member of this family, a protein related to Myosin light chain
      kinase, was also identified. The cDNA and genomic sequences published explain
      only the shorter transcripts expressed by this locus. Here, we report the
      complete molecular characterization of this transcription unit, which spans 38
      kb, includes 33 exons and accounts for transcripts up to 25 kb in length. This
      transcription unit contains both the largest exon (12,005 nt) and the largest
      coding region (25,213 nt) reported so far for Drosophila. This transcription unit
      features both internal promoters and internal polyadenylation signals, which
      enable it to express seven different transcripts, ranging from 3.3 to 25 kb in
      size. The latter encodes a huge, titin-like, 926 kDa kinase that features two
      large PEVK-rich repeats, 32 immunoglobulin and two fibronectin type-III domains,
      which we designate stretchin-MLCK. In addition, the 3' end of the stretchin-MLCK
      transcription unit expresses shorter transcripts that encode 86 to 165 kDa
      isoforms of stretchin-MLCK that are analogous to vertebrate Myosin light chain
      kinases. Similarly, the 5' end of the Stretchin-Mlck transcription unit can also
      express transcripts encoding kettin and Unc-89-like isoforms, which share no
      sequences with the MLCK-like transcripts. Thus, this locus can be viewed as a
      single transcription unit, Stretchin-Mlck (genetic abbreviation Strn-Mlck), that
      expresses large, composite transcripts and protein isoforms (sequences available
      at http://www.academicpress.com/jmb), as well as a complex of two independent
      transcription units, the Stretchin and Mlck transcription units (Strn and Mlck,
      respectively) the result of a "gene fission" event, that encode independent
      transcripts and proteins with distinct structural and enzymatic functions.

PMID- 10891288
TI  - Chemokine receptor-related genetic sequences in an african green monkey simian
      cytomegalovirus-derived stealth virus.
AB  - The US28 gene of human cytomegalovirus (HCMV) codes a cell surface receptor for
      both beta chemokine and fractalkine molecules. This receptor facilitates HCMV
      induced cell fusion and virus dissemination and influences susceptibility to
      infection with other viruses, including the human immunodeficiency virus. Five
      adjacent but divergent open reading frames that potentially code for molecules
      related to the US28 protein of HCMV are present in an African green monkey simian
      cytomegalovirus-derived stealth virus. This finding implies a role for chemokines
      in the pathogenicity of at least some stealth-adapted viruses. It may also help
      explain the apparent therapeutic benefit achieved in certain stealth virus
      infected patients treated with agents that downregulate chemokine production.

PMID- 10891289
TI  - Induction of cytochrome P450 enzymes in the livers of rats treated with the
      pyrrolizidine alkaloid retrorsine.
AB  - Retrorsine is a member of the pyrrolizidine alkaloid (PA) family of naturally
      occurring compounds found in a large number of plant species worldwide. The
      cytotoxic, mutagenic, and antimitotic effects of PAs have made them targets for
      studies designed to determine their potential contributions to carcinogen esis
      and their usefulness for anticancer therapy. Evidence from the literature
      suggests that bioactivation of PAs by liver cytochrome P450 (CYP) enzymes is
      required for their toxicity. However, the specific CYP isozymes that are involved
      in retrorsine metabolism have not been identified. To address this issue, we
      administered retrorsine to a cohort of young adult male rats and examined
      induction or enhanced expression of mRNA and protein for widely studied hepatic
      CYP isoforms spanning four families together with the essential enzyme CYP
      reductase. The protein levels of normally expressed CYPs 1A2, 2B1/2, and 2E1
      increase significantly in rat liver microsomes from retrorsine-treated rats
      compared to untreated control rats (P < 0. 05), but protein levels of CYP 4A3,
      CYP 3A1, and CYP reductase were unchanged after retrorsine treatment. In
      addition, CYP 1A1 mRNA and protein, which are not detectable in the livers of
      control rats, were induced after retrorsine exposure. The results of the present
      study demonstrate enhanced or induced expression of hepatic CYPs 1A1, 1A2, 2E1,
      and 2B1/2 in response to retrorsine exposure in rats, suggesting that one or more
      of these enzymes may be involved in retrorsine metabolism.

PMID- 10891290
TI  - Immunohistochemical versus molecular detection of RAK antigens in breast cancer.
AB  - RAK antigens p120, p42, and p25 exhibit molecular and immunological similarity to
      the proteins encoded by HIV-1 and are expressed by 95% of breast and
      gynecological cancer cases in women and prostate cancer cases in men. Binding of
      the monoclonal antibody (MAb) RAK-BrI to cancer RAK antigens has been found to be
      inhibited by a peptide derived from the variable loop V3 of HIV-1. Since MAb RAK
      BrI has been developed against denatured froms of breast cancer proteins, and it
      binds to a short epitope, GRAF, this MAb does not recognize the native, three
      dimensional structure of proteins. Subsequently Western blot, after
      electrophoretic separation in gels with SDS, has been used to detect these unique
      cancer markers. The current studies were focused on the immunohistochemical
      evaluation of the novel marker RAK. Serial sections, 5 microm thick, were cut
      from frozen or Formalin-fixed, paraffin-embedded tissue blocks and immunostained
      with MAb RAK-BrI. All of the 53 cases of breast cancer tested RAK positive and no
      differences were observed in the immunohistochemical staining of lobular and
      ductal carcinoma cases. In contrast, MAb RAK-BrI antigens were detected in only 3
      of 15 cases of macroscopically normal breast removed during mastectomy for breast
      cancer. It is noteworthy that Western blots of breast samples from the same
      series demonstrated a high expression of three RAK antigens in 20/20 of invasive
      breast carcinomas, while there was only a very weak expression of RAK antigens in
      2/7 of the macroscopically "normal" breast samples. Due to the suspected viral
      origin of RAK markers, immunohistochemical staining with MAb RAK-BrI might be a
      useful tool in the early detection of malignant changes occurring in breast
      tissues.

PMID- 10891291
TI  - Postmitotic differentiation of colon carcinoma caco-2 cells does not prevent
      reentry in the cell cycle and tumorigenicity.
AB  - Our purpose was to analyze whether postmitotic Caco-2 colon cancer cells,
      although they express most of the differentiation characteristics of terminally
      differentiated intestinal epithelial cells, still maintain, unlike normal cells,
      a proliferation potential. Experiments were performed with clone TC7 of the Caco
      2 cell line. Dividing TC7 cells are undifferentiated and express detectable
      levels of thymidylate synthase (TS) and cytochrome P450 1A1 (CYP1A1) mRNAs. When
      reaching confluence TS and CYP1A1 are downregulated, mitosis is no longer
      detectable, and differentiation takes place, as demonstrated by appearance and
      increasing levels of differentiation-associated marker mRNAs (e.g., sucrase
      isomaltase (SI), dipeptidylpeptidase-IV (DPP-IV) or GLUT5), increasing activities
      of sucrase and DPP-IV, and increasing expression, on immunofluorescence analysis,
      of SI on the surface of the cell layer. Trypsinization and seeding of late
      postconfluent cells (day 30) expressing complete differentiation results within
      24 h in upregulation of TS and CYP1A1, a concomitant and dramatic disappearance
      of differentiation marker mRNAs associated with a decrease in sucrase and DPP-IV
      activities, and delayed resumption of cell division. This is followed, after the
      cells have reached confluence again, by downregulation of TS and CYP1A1 and
      resumption of cell differentiation. The ability of differentiated cells to
      dedifferentiate was further confirmed by wounding the cell layer of late
      postconfluent differentiated cultures: within 24 h following the wound, cells
      migrate from the wound edge and dedifferentiate, as demonstrated by transmission
      electron microscopy and disappearance of SI from the cell surface of migrating
      cells. Late postconfluent differentiated cells were tumorigenic in nude mice.
      These results raise the question of the validity of the concept of
      differentiation therapy when applied to colon cancer cells.

PMID- 10891292
TI  - Proteinase imbalance versus biomechanical stress in pulmonary emphysema.
AB  - Emphysema is a slowly progressive degenerative lung disease involving
      fragmentation and depletion of elastic fibers, loss of lung elastance, and
      architectural destruction with ectasia, tortuosity, and loss of bronchioles
      irrespective of localization or morphological type. Occurring under physiological
      conditions, predominantly in geriatrics, matrix laxity and destructive
      parenchymal lesions are indicative of a pathological loss of tissue tensile
      strength attributable to bioengineering or structural fatigue in repetitively
      stressed tissues. The occurrence of severe premature emphysema in inherited
      connective tissue diseases and under some experimental and iatrogenic conditions
      is supportive evidence. Experiments advocating unrestrained proteolysis as a
      cause or pathogenic factor are invalid, being based on a false premise and
      assumed causality.

PMID- 10891293
TI  - Tumor angiogenesis: thrombin and metalloproteinases in focus.

PMID- 10891294
TI  - Information Processing at Successive Stages of Decision Making: Need for
      Cognition and Inclusion-Exclusion Effects.
AB  - Levin and Jasper's (1995) phased narrowing technique for tracking changes in
      information usage across successive stages of the decision-making process was
      combined with Huneke's (1996) "pull-down menu" extension of Payne, Bettman, and
      Johnson's (1988) software package for generating measures of information
      processing. Because this technique provided considerable data for each individual
      subject at each stage, we were able to focus on individual differences in
      information processing across stages, most notably differences related to need
      for cognition (NC; Cacioppo & Petty, 1982). In a computerized information search
      and decision task, 60 college students were first asked to narrow their options
      for purchasing a notebook computer to form a consideration set and were then
      asked to make a final choice from this set. At the consideration set formation
      stage, half the subjects were instructed to adopt a mindset to include options
      while the other half were asked to exclude options. Especially in the inclusion
      condition where subjects showed greater narrowing of options, high NC subjects
      processed information in a more focused manner with greater depth and breadth
      than did low NC subjects, and the quality of their selections tended to be
      higher. There was no evidence of widespread shifts in strategy as individuals
      moved from set formation to final choice but, as a group, high NC subjects were
      more successful at adaptive decision making. Copyright 2000 Academic Press.

PMID- 10891295
TI  - Increasing Cooperation in Prisoner's Dilemmas by Establishing a Precedent of
      Efficiency in Coordination Games.
AB  - Coordination games have multiple Nash equilibria (i.e., sets of strategies which
      are best responses to one another). In weak-link coordination games players
      choose a number 1-7. Their payoff is increasing in the minimum number (or weakest
      link) and decreasing in the difference between their number and the minimum.
      Choosing 7 is an efficient equilibrium because it gives everybody a higher payoff
      than any other coordinated choice. Higher-payoff equilibria are riskier, however,
      so the game expresses the tradeoff between group efficiency and personal risk
      present in many social and organizational settings. We tested whether choosing
      efficiently in a weak-link game increases cooperative play in a subsequent
      prisoner's dilemma (PD) game. This cross-game transfer resembles the transfer of
      cooperative norms in small firms (which are more like coordination games than
      PDs) as firms grow larger and become like PDs. In two experiments, if a group of
      players share a history of playing the weak-link game efficiently, that
      efficiency precedent can transfer to a subsequent PD game, improving the level of
      cooperativeness. The effect of transfer is much larger in magnitude (increasing
      cooperation from 15-30% to 71%) than the effects of most variables in previous PD
      studies. However, the transfer effect depends on descriptive similarity of
      strategies in the two games, since it largely disappears when the strategies are
      numbered differently in the weak-link game and the PD. Copyright 2000 Academic
      Press.

PMID- 10891296
TI  - Partitive Formulation of Information in Probabilistic Problems: Beyond Heuristics
      and Frequency Format Explanations.
AB  - I propose a simple theory on the use of base rate according to which neither
      heuristic nor frequentist factors underlie demonstrations of the occurrence or
      the elimination of the base-rate fallacy. According to this view, what is crucial
      for the occurrence or elimination of the base-rate fallacy is the absence or
      presence, respectively, of what can be called a partitive formulation (Macchi,
      1995) of the conditional likelihood datum. A partitive formulation defines the
      set of which the numerical datum is a part (in terms of percentages or
      frequencies) by referring to the likelihood datum relative to the base rate
      information. The predictive power of this hypothesis is shown by comparing
      responses to different versions of problems containing the same implied natural
      heuristic principles and supplied data, but which differ in the way the
      information is presented (partitive vs nonpartitive). Whether probabilistic or
      frequentist, the partitive versions lead to an almost complete elimination of the
      bias which remains when nonpartitive versions are used. On the basis of these
      experimental results, the paper includes a critical discussion of heuristic,
      frequentist, and mental models theories. Copyright 2000 Academic Press.

PMID- 10891297
TI  - Reducing the Effects of Performance Expectations on Behavioral Ratings.
AB  - In this study, we develop and test two strategies for reducing the effects of
      performance expectations on behavioral ratings. A 3 x 3 experimental design (N =
      169), manipulating preobservation performance cues (positive, negative, or none)
      and the type of intervention (halo error training, structured recall memory, or
      none), was conducted. The results of this study indicate that both interventions
      reduced the effects of performance expectations on behavioral ratings. However,
      analyses of rating accuracy and measures from both recognition memory and recall
      memory tests suggest that the structured recall memory intervention has distinct
      advantages. These analyses indicate that the structured recall intervention can
      reduce raters' reliance on heuristics and increase the correspondence between
      raters' memory and their subsequent ratings. Copyright 2000 Academic Press.

PMID- 10891298
TI  - Familiarity Bias and Belief Reversal in Relative Likelihood Judgment.
AB  - People are often called on to make an assessment of the relative likelihood of
      events (e.g., which of two investments is more likely to outperform the market?)
      and their complements (which of the two investments is more likely to perform no
      better than the market?). Probability theory assumes that belief orderings over
      events and their complements should mirror each other (i.e., P(A) >/= P(B) iff P
      (not-A) </= P(not-B)). This principle is violated in several surveys in which we
      asked people to assess the relative likelihood of familiar versus unfamiliar
      events. In particular, respondents are biased to view more familiar events (and
      their complements) as more likely than less familiar events (and their
      complements). Similarly, we observe that subjects are biased to view less
      familiar events (and their complements) as less likely than more familiar events
      (and their complements). Further studies demonstrate that the familiarity bias is
      less pronounced among subjects who are asked to judge the probability of each
      event rather than which event is more likely. Moreover, a greater proportion of
      subjects rate the more familiar event as more likely than assign a higher
      probability to that event. These patterns can be construed as belief reversals,
      analogous to the preference reversal phenomenon in decision making. The data are
      consistent with a contingent weighting model in which the process of judging
      relative likelihood biases attention toward evidence supporting the target
      hypothesis (and away from evidence supporting its complement). Because it is
      easier to recruit evidence supporting familiar events than unfamiliar events,
      this skewed attention causes both familiar events and their complements to be
      judged more likely, on average, than unfamiliar events and their complements.
      Copyright 2000 Academic Press.

PMID- 10891299
TI  - Acceptance and Elimination Procedures in Choice: Noncomplementarity and the Role
      of Implied Status quo.
AB  - The present research contrasts two seemingly complementary decision strategies:
      acceptance and elimination. In acceptance, a choice set is created by including
      suitable alternatives from an initial set of alternatives, whereas in elimination
      it is created by removing inappropriate alternatives from that same initial set.
      The research used realistic career decision-making scenarios and presented to
      respondents sets of alternatives that varied in their preexperimental strength
      values. Whereas complementarity of acceptance and elimination is implied by three
      standard (normative) assumptions of decision theory, we find a systematic
      discrepancy between the outcomes of these procedures: choice sets were larger in
      elimination than in acceptance. This acceptance-elimination discrepancy is
      directly tied to subcomplementarity. The central tenet of the theoretical
      framework developed here is that acceptance and elimination procedures imply
      different types of status quo for the alternatives, thereby invoking a different
      selection criterion for each procedure. A central prediction of the dual
      criterion framework is that middling alternatives should be most susceptible to
      the type of procedure used. The present studies focus on this prediction which is
      substantiated by the results showing that middling alternatives yield the
      greatest discrepancy between acceptance and elimination. The implications of this
      model and findings for various research domains are discussed. Copyright 2000
      Academic Press.

PMID- 10891300
TI  - Is 7300 m Equal to 7.3 km? Same Semantics but Different Anchoring Effects.
AB  - Anchoring effect (AE) refers to a phenomenon that an arbitrary number (i.e., the
      anchor) biases a subsequent numerical judgment. Three experiments were conducted
      to examine how the anchor is represented in short-term memory. Experiment 1
      showed that despite the semantic equivalence of two anchors, the anchor with a
      larger absolute value (i.e., 7300 m) induced a greater numerical estimate than
      did the anchor with a smaller absolute value (i.e., 7.3 km). Experiment 2 showed
      that an anchor 228 could serve as both a high and a low anchor, depending on the
      absolute value to be judged in the numerical judgment. By including anchors with
      negative signs, Experiment 3 further demonstrated that it was the absolute value
      but not the semantics of the anchors that exerted an effect on the subsequent
      numerical estimate. The three experiments provided converging support for the
      hypothesis that an anchor is superficially represented as absolute value plus
      affix in short-term memory. The processes leading to AE and the practical
      implications are discussed. Copyright 2000 Academic Press.

PMID- 10891301
TI  - Analyzing Goal-Striving Processes and a Test of the Generalizability of
      Perceptual Control Theory.
AB  - Theories that articulate dynamic processes are relatively rare, but methods for
      testing the theories are even rarer. This study illustrates two methods for
      examining goal-striving processes and a tool for collecting dynamic data. The
      first method tests a hypothesis regarding what variable the participants are
      attempting to maintain. The second method involves creating multilevel models
      used to describe the dynamic data generated by study participants, which can be
      used to test between- and within-subject manipulations or differences. The tool
      is a research simulation of a manager's role in scheduling subordinates in a
      hospital wing. Together these methods and the tool are used to test the
      generalizability of perceptual control theory in explaining striving for
      cognitive goals. The results confirm the viability of a control theory accounting
      of goal striving and highlight the potential of the methods and the research tool
      in future research. Copyright 2000 Academic Press.

PMID- 10891326
TI  - Sterol 14-demethylase P450 (CYP51) provides a breakthrough for the discussion on
      the evolution of cytochrome P450 gene superfamily.
AB  - Biodiversity is the most characteristic feature of cytochrome P450. Finding of
      CYP51 distributing widely in biological kingdoms provided breakthroughs for the
      discussion on the evolution and diversification of P450. Molecular phylogenetic
      analysis demonstrated that CYP51 appeared in the prokaryotic era and distributed
      into most kingdoms concomitant with phylogenetic divergence. This is the first
      evolutionary evidence indicating the prokaryotic origin of P450. Modification of
      substrate specificity of eukaryotic CYP51s occurred independently to adapt to the
      different sterol precursors existing in each kingdom. Formation of CYP51 variants
      through the mutation of active site and the selection of the advantageous ones
      from them were demonstrated by the emergence of azole-resistant CYP51s in Candida
      albicans under the environments rich in azole antifungal agents. These findings
      illustrate the most probable core process of P450 diversification consisting of
      modification of active site and selection of the resulting variants through
      interaction with endogenous and exogenous chemicals.

PMID- 10891327
TI  - Identification of an EDG7 variant, HOFNH30, a G-protein-coupled receptor for
      lysophosphatidic acid.
AB  - We have identified a cDNA, designated HOFNH30, which encodes a 354 amino acid G
      protein-coupled receptor (GPCR). This receptor has 96% amino acid identity to the
      Jurkat-T cell-derived EDG7 and could be a splice variant. RT-PCR analysis
      demonstrated that HOFNH30 mRNA is expressed in placenta whereas EDG7 mRNA shows
      highest expression in prostate. The HOFNH30 gene is localized to human chromosome
      1p22. 3-1p31.1. When HOFNH30 was expressed in RBL-2H3 cells, LPA and phosphatidic
      acid (PA) induced a calcium mobilization response with EC(50) values of 13 nM and
      3 microM, respectively. LPA also induced phosphorylation of mitogen-activated
      protein kinase (p42(MAPK) and p44(MAPK)) in HOFNH30-transfected but not vector
      transfected RBL-2H3 cells. In the present study, we have identified a novel
      variant from the EDG receptor family, a GPCR for which LPA is a high-affinity
      endogenous ligand.

PMID- 10891328
TI  - Stimulus-specific inhibition of IL-5 by cAMP-elevating agents and IL-10 reveals
      differential mechanisms of action.
AB  - Interleukin-5 (IL-5) is a Th2 cytokine, which is implicated in the pathogenesis
      of eosinophilic diseases such as asthma. Peripheral blood mononuclear cells
      (PBMC), costimulated with phorbol 12-myristate 13-acetate (PMA) plus
      phytohemagglutinin (PHA) or activating antibodies to the CD3 and CD28 T
      lymphocyte surface markers, produced similar patterns of IL-5 expression.
      However, in PMA + PHA-treated cells, 8-bromo-cAMP and PGE(2) did not affect IL-5
      expression, whereas in CD3 + CD28-stimulated cells, almost total repression was
      observed. IL-10 failed to inhibit IL-5 mRNA from PMA + PHA-treated cells, yet
      reduced release by 40%. By contrast, IL-10 totally inhibited CD3 + CD28-induced
      IL-5 release and inhibited mRNA by 50-60%. These results highlight important
      biological differences in the induction of IL-5 by the nonspecific stimulus PMA +
      PHA and the more physiological CD3 + CD28 costimulation. Finally, the potential
      for downregulating Th2 responses by cAMP-elevating agents or IL-10 is
      demonstrated and a significant role for posttranscriptional mechanisms in the
      inhibition by IL-10 is suggested.

PMID- 10891329
TI  - Histidin as a mercurial poisoning inhibitor.
AB  - Histidin has been shown to effectively inhibit coagulation of horse oxyhemoglobin
      (HbO(2)) modified by mercury(II) ion bound to reactive thiol groups of protein.
      Kinetic parameters were measured and the histidin-to-mercury binding constant was
      kinetically estimated. Histidin, as other pharmaceutically acceptable compounds
      with some mercury-binding capacity, has been suggested to alleviate mercury
      intoxication conditions.

PMID- 10891330
TI  - Chemical modification of hemoglobin improves biocatalytic oxidation of PAHs.
AB  - Chemical modifications on human hemoglobin were performed with the aim to change
      both surface and active-site hydrophobicities. The modifications included
      covalent coupling of poly(ethylene)glycol (5000 MW) on free amino groups and the
      methyl esterification of free carboxylic groups. The modified hemoglobin was
      assayed for the oxidation of 11 polycyclic aromatic hydrocarbons (PAHs) and 2
      organosulfur aromatic compounds. Acenaphthene, anthracene, azulene,
      benzo(a)pyrene, fluoranthene, fluorene, phenanthrene, and pyrene were transformed
      to their respective quinones, while for chrysene and biphenyl no biocatalytic
      reaction could be detected. Dibenzothiophene and thianthrene were oxidized to
      form sulfoxides. The doubly modified hemoglobin, PEG-Met-hemoglobin, showed up to
      10 times higher activity than the unmodified protein. The kinetic constants show
      that the PEG-Met-hemoglobin has a significantly higher catalytic efficiency. The
      equilibrium substrate binding constants for unmodified and PEG-Met-modified
      hemoglobis and hemoglobin show that this catalytic enhancement could be
      attributed to the affinity increase for hydrophobic substrates in the modified
      protein.

PMID- 10891331
TI  - Disruption of galactokinase signature sequence in gal3p of Saccharomyces
      cerevisiae does not lead to loss of signal transduction function.
AB  - Gal3p of Saccharomyces cerevisiae is a 520-amino-acid residue protein, which
      activates the GAL genes in the presence of galactose by relieving the repression
      of Gal80p. It shows significant amino acid sequence homology to galactokinases
      but does not possess galactokinase activity. Deletion mutants of Gal3p were
      generated to identify the role of N-terminal amino acid residues required for
      function. The mutant versions of Gal3p could be detected on a Western blot. The
      Gal3p mutant lacking N-terminal 50-amino-acid residues which is disrupted for
      galactokinase signature sequence was found to be functional. These results
      suggest that the evolutionarily conserved galactokinase signature sequence
      present in known galactokinases may not have a role in Gal3p function.

PMID- 10891332
TI  - Enzyme destruction by a protease contaminant in bacitracin.
AB  - Bacitracin, as purchased from biochemical supply companies, is a mixture of more
      than 30 different substances. The major antibiotic isoforms A and B account for
      about 60% of the mixture. A newly identified impurity in some, but not all, of
      the bacitracin lots is a powerful subtilisin-type protease capable of cleaving
      many proteins including protein disulfide isomerase (PDI), myosin, and a variety
      of artificial substrates Thus, it is important for investigators who use
      bacitracin as a protease or other enzyme inhibitor to determine if the bacitracin
      they are using is contaminated with a protease enzyme. If it is present, they may
      have to reinterpret their results and retest with an enzyme-free bacitracin
      reagent.

PMID- 10891333
TI  - Effect of suppression of TGF-beta1 expression on cell-cycle and gene expression
      of beta-1,4-galactosyltransferase 1 in human hepatocarcinoma cells.
AB  - beta-1,4-galactosyltransferase 1 (beta1,4-GT 1) is localized both in the Golgi
      complex where it catalyzes the transfer of galactose from UDP-galactose to
      terminal N-acetylglucosamine forming Galbeta1 --> 4GlcNAc structure, and on the
      cell surface where it serves as an adhesion molecule. It has previously been
      reported that the expression of beta1,4-GT 1 was cell-cycle-specific, regulated
      by cell growth. Transforming growth factor-beta1 (TGF-beta1) could regulate cell
      G1/S phase transition and modulate cell growth in many types of cells. In this
      study, we introduced the antisense-TGF-beta1 into SMMC-7721 cell, a human
      hepatocarcinoma cell line, for blocking its intrinsic TGF-beta1 expression, and
      changing its cell-cycle, and then analyzed the gene expression of beta1,4-GT 1
      together with the beta1,4-GT activity. The result showed that the antisense-TGF
      beta1 transfected SMMC-7721 cells (AST/7721) were growth enhanced, with more
      cells in S phase and less cells in G2/M phase compared with the mock transfected
      cells (pcDNA3/7721). At the same time, it was found that the gene expression of
      beta1,4-GT 1 in AST/7721 was decreased to one fifth that of pcDNA3/7721, and the
      cell surface beta1,4-GT activity was reduced to one fifth of the control, while
      the total activity of beta1,4-GT was decreased to one half that of the control.
      The results indicate that suppression of TGF-beta1 expression resulted in change
      of cell-cycle together with the decreased gene expression of beta1,4-GT 1 and
      beta1,4-GT activity in human hepatocarcinoma cells.

PMID- 10891334
TI  - Heme degradation during autoxidation of oxyhemoglobin.
AB  - Two fluorescent heme degradation compounds are detected during autoxidation of
      oxyhemoglobin. These fluorescent compounds are similar to fluorescent compounds
      formed when hydrogen peroxide reacts with hemoglobin [E. Nagababu and J. M.
      Rifkind, Biochem. Biophys. Res. Commun. 247, 592-596 (1998)]. Low levels of heme
      degradation in the presence of superoxide and catalase are attributed to a
      reaction involving the superoxide produced during autoxidation. The inhibition of
      most of the degradation by catalase suggests that the hydrogen peroxide generated
      during autoxidation of oxyhemoglobin produces heme degradation by the same
      mechanism as the direct addition of hydrogen peroxide to hemoglobin. The
      formation of the fluorescent degradation products was inhibited by the peroxidase
      substrate, ABTS, which reduces ferrylhemoglobin to methemoglobin, indicating that
      ferrylhemoglobin is produced during the autoxidation of hemoglobin. It is the
      transient formation of this highly reactive Fe(IV) hemoglobin, which is
      responsible for most of the heme degradation during autoxidation.

PMID- 10891335
TI  - G6PD deficient cells and the bioreduction of disulfides: effects of DHEA, GSH
      depletion and phenylarsine oxide.
AB  - We used Glucose 6 phosphate dehydrogenase (G6PD) minus cells (89 cells) and G6PD
      containing cells (K1) to understand the mechanisms of bioreduction of disulfide
      and the redox regulation of protein and non protein thiols in mammalian cells.
      The 89 cells reduce hydroxyethyldisulfide (HEDS) to mercaptoethanol (ME) at a
      slower rate than K1 cells. HEDS reduction results in loss of nonprotein thiols
      (NPSH) and a decrease in protein thiols (PSH) in 89 cells. The effects are less
      dramatic with K1 cells. However, the loss of NPSH and PSH in K1 cells are
      increased in the absence of glucose. Glutathione-depletion with L-BSO partially
      blocks HEDS reduction in K1 and 89 cells. Treatment with the vicinal thiol
      reagent phenyl arsenic oxide (PAO) blocks reduction of HEDS in both cells.
      Surprisingly, dehydroepiandrosterone (DHEA), a known inhibitor of G6PD, inhibits
      the growth and blocks the reduction of HEDS both in 89 and K1 cells suggesting
      that its mechanism for inhibition of growth is not G6PD related.

PMID- 10891336
TI  - Activation of NF-kappaB binding in HT-29 colon cancer cells by inhibition of
      phosphatidylinositol 3-kinase.
AB  - The ubiquitous transcription factor NF-kappaB, which is activated in cells by
      diverse stimuli including phosphatidylinositol 3-kinase (PI3-kinase), is a
      critical factor for cell survival and growth. Inhibition of PI3-kinase enhances
      enterocyte-like differentiation of the human colon cancer cell line HT-29. The
      purpose of our study was to determine whether PI3-kinase alters NF-kappaB in HT
      29 cells. Wortmannin, a specific PI3-kinase inhibitor, stimulated NF-kappaB
      binding activity in HT-29 cells by 4 h after treatment. Activation of NF-kappaB
      occurred without degradation of IkappaBalpha, a protein that sequesters NF-kappaB
      in the cytosol. In addition to increasing NF-kappaB binding, either wortmannin or
      cotransfection with a dominant negative mutant of the p85 regulatory subunit of
      PI3-kinase (Deltap85) induced NF-kappaB transactivation. Taken together, these
      results suggest that inhibition of PI3-kinase in HT-29 cells results in induction
      of NF-kappaB binding activity and transactivation which is independent of
      IkappaBalpha degradation.

PMID- 10891337
TI  - Glucose deprivation does not affect GLUT1 targeting in 3T3-L1 adipocytes.
AB  - We have previously demonstrated that glucose deprivation alters the glycosylation
      of the GLUT1 glucose transporter in 3T3-L1 adipocytes. Many aberrantly
      glycosylated proteins are retained in the endoplasmic reticulum by interaction
      with chaperones. Herein, we use three independent procedures to show that GLUT1
      is targeted to the plasma membrane, despite alterations in glycosylation. While
      earlier experiments revealed that plasma membrane targeting of aglyco GLUT 1
      transporter was significantly reduced, our data show for the first time that
      altered glycosylation provides sufficient information to drive appropriate
      trafficking.

PMID- 10891338
TI  - Human T-cell lymphotropic virus type-I tax gene induces interleukin-8 secretion
      by autocrine mechanism and has No effect on interleukin-16 in transfected Jurkat
      cells.
AB  - Human T-cell lymphotropic virus I (HTLV-I) Tax has been shown to transactivate
      several cellular genes. In this study, we show that interleukin-8 (IL-8) is
      expressed and secreted in tax-transfected Jurkat cells that were further
      augmented by mitogen stimulation. Expression of high-affinity IL-8-R (Type A)
      mRNA in these cells suggests an autocrine role for this chemokine in HTLV-I
      infected T-cells. However, interleukin-16 (IL-16) mRNA expression or protein
      secretion was not significantly modulated either constitutively or even upon
      mitogen stimulation in these tax-transfected cells.

PMID- 10891339
TI  - A GDP-fucose-protected, pyridoxal-5'-Phosphate/NaBH(4)-sensitive lys residue
      common to human alpha1-->3Fucosyltransferases corresponds to Lys(300) in FucT-IV.
AB  - Human alpha1-->3/4fucosyltransferases (FucTs) contain a common essential
      pyridoxal-5'-phosphate(PLP)/NaBH(4) reactive, GDP-fucose-protectable Lys. For
      identification, site-directed mutants at lysines of FucT-IV and -VII were
      prepared and tested. Non conserved lysine mutants K119Y and K394Q were similar to
      wild-type FucT-IV. However, mutants of conserved lysines K228R and K300R were
      distinct. The specific activity of K228R was 2- to 3-fold lower but retained K(m)
      values for donor and acceptor substrates as wild-type FucT-IV. The specific
      activity of K300R was reduced over 400-fold with an apparent K(m) for GDP-fucose
      over 200 microM. FucT-VII mutants K169R and K240R (equivalent to K228R and K300R
      for FucT-IV, respectively) were inactive. No change in PLP/NaBH(4) sensitivity
      occurred with K119Y, K228R, and K394Q compared to wild-type FucT-IV. These and
      previous results (A. L. Sherwood, A. T. Nguyen, J. M. Whitaker, B. A. Macher, M.
      R. Stroud, and E. H. Holmes, J. Biol. Chem. 273, 25256-25260, 1998) demonstrate
      that of three conserved lysines in FucT-IV, two (Lys(228) and Lys(283)) are not
      involved in substrate binding but perhaps in catalysis. The third site, Lys(300),
      is involved in GDP-fucose binding and PLP/NaBH(4) inactivation.

PMID- 10891340
TI  - Genomic organization, chromosomal localization, and expression of the murine
      RAB3D gene.
AB  - Rab proteins, members of the Ras superfamily of small GTPases, play regulatory
      roles in intercompartmental vesicular transport. Each step of traffic seems to
      require the participation of at least one distinct Rab, with the Rab3 subfamily
      involved in stimulated exocytosis. We report our studies on the murine rab3D
      gene, one of the four mammalian Rab3 isoforms. We located this gene on chromosome
      13, region A(2-3). The rab3D gene consists of 5 exons spanning 10.6 kb, and the
      structural gene is contained in exons 2 through 5 with one canonical GTP-binding
      motif in each exon. Organization of the rab3D gene is identical to that of rab3A
      but different from other rab genes. Alternative poly-A(+) signals in the 3'
      untranslated region account for the identities of multiple transcripts detected
      by Northern blot analysis. Rab3D is expressed in all tissues studied,
      predominantly in heart, lung, and liver, and binding sites for multiple
      transcription factors are found in the TATA-less promoter region.

PMID- 10891341
TI  - Molecular cloning, expression, and functional characterization of a novel member
      of the CD38 family of ADP-ribosyl cyclases.
AB  - We report the molecular cloning and functional characterization of a novel member
      of the CD38 family of cyclic ADP-ribose (cADPr)-generating cyclases. We cloned a
      cDNA insert that encoded a 298-amino-acid-long protein (M(w) approximately 39
      kDa). The predicted protein displayed 69, 61, and 58% similarity, respectively,
      to mouse, rat, and human CD38. Rabbit CD38 was also 28% homologous to Aplysia ADP
      ribosyl cyclase and leukocyte CD157 (another ADP-ribosyl cyclase); the three
      cyclases shared 10 cysteine and 2 adjacent proline residues. We then transfected
      CD38-negative NIH3T3 cells with cDNA encoding a CD38-EGFP fusion protein.
      Epifluorescence microscopy showed intense EGFP fluorescence confirming CD38
      expression. We finally confirmed the ADP-ribosyl cyclase activity of the
      expressed CD38 by measuring its ability to catalyze the cyclization of the
      nicotinamide adenine dinucleotide (NAD(+)) surrogate, NGD(+), to its fluorescent
      nonhydrolyzable derivative, cGDPr.

PMID- 10891342
TI  - Analysis of prion protein mRNA by in situ hybridization in brain and placenta of
      sheep.
AB  - In this study, prion protein (PrP) mRNA was focally detected in brain and
      placenta of pregnant sheep by Northern blot analysis. In addition, host-encoded
      cellular prion protein (PrP(C)) was observed in brain and placenta of the
      ruminant by Western blot analysis as well. Localization of PrP mRNA in pregnant
      sheep tissues was rendered possible with in situ hybridization. In sheep brain,
      PrP mRNA was predominantly localized within large neocortical neurons in the
      cerebrum, Purkinje cells and neurons of the molecular and granule cell layers in
      the cerebellum. In the placenta, signals were observed in the myometrium,
      including stratum longitudinale tunicae muscles and circular layers of muscular
      tunics. In the caruncle and placentome, signals were stronger by in situ
      hybridization. Since accumulation of the scrapie isoform PrP (PrP(Sc)) is
      required to PrP(C), these results suggest that brain and placenta of sheep may be
      important organs and sites for the conversion of PrP(C) to PrP(Sc).

PMID- 10891343
TI  - Aberrant processing of oxidative DNA damage in systemic lupus erythematosus.
AB  - Defective DNA damage processing has been reported in systemic lupus erythematosus
      (SLE). Vitamin C may modulate formation/removal of the oxidative DNA lesion 8-oxo
      2'-deoxyguanosine (8-oxodG). Baseline levels of 8-oxodG measured in SLE serum,
      urine and PBMC DNA did not differ significantly from healthy subjects. In
      contrast to healthy subjects, no significant decrease in PBMC 8-oxodG or increase
      in urinary 8-oxodG was noted in vitamin C supplemented SLE patients. A
      significant, although attenuated, increase in serum 8-oxodG was detected in SLE
      patients, compared to healthy subjects. These data support putative abnormalities
      in the repair/processing of 8-oxodG in SLE.

PMID- 10891344
TI  - Spectrin changes occur in erythrocytes from patients with Fanconi's anemia and
      their parents.
AB  - Fanconi's anemia (FA) is a clinically and genetically heterogeneous disease which
      has been hypothesized to be defective in the detoxification of reactive oxygen
      species. In this work we report the results obtained by morphometric analyses on
      the red blood cells (RBCs) from FA patients and their parents. We found that a
      high rate of erythrocytes from both homozygous and heterozygous subjects was
      significantly altered. RBCs underwent in fact cytoskeleton-dependent
      modifications, in particular of spectrin molecule, leading to cell shrinking and
      blebbing. We hypothesize that these changes may be the result of an oxidative
      imbalance that probably lead to alterations of RBC plasticity- and deformation
      associated functions. Moreover, our results also suggest the possibility to
      identify FA carriers by the existence of RBC abnormalities.

PMID- 10891345
TI  - Preparation of recombinant human GDNF by baculovirus expression system and
      analysis of its biological activities.
AB  - Recombinant human glial cell line-derived neurotrophic factor (GDNF) has been
      expressed at high levels and produced in large quantities in baculovirus-infected
      Trichoplusia ni cells (Tn-5B1-4). The glycosylated protein was purified using
      immunoaffinity chromatography and gel filtration. Pure, recombinant human GDNF
      promoted the survival and morphological differentiation of embryonic dopaminergic
      neurons and enhanced axonal regeneration after sciatic nerve transection. Because
      recombinant bioactive human GDNF can be obtained in large quantities, and
      purified to near homogeneity, they are suitable for evaluation in animal models.

PMID- 10891346
TI  - Expression and distribution of InsP(3) receptor subtypes in proliferating
      vascular smooth muscle cells.
AB  - The expression and distribution of types 1, 2, and 3 inositol 1,4, 5
      trisphosphate receptor (InsP(3)R) in proliferating, primary cultures of rat
      aortic smooth muscle were compared to fully developed and differentiated rat
      aortic smooth muscle. Subtype-specific InsP(3)R antibodies revealed that the
      expression of type 1 InsP(3)R was similar in cultured aortic cells and aorta
      homogenate but expression of type 2 and 3 InsP(3)R subtypes was increased 3-fold
      in cultured aortic cells. The distribution of the type 1 InsP(3)R was located
      throughout the cytoplasm; type 2 InsP(3)R was found closely associated with the
      nucleus and at the plasma membrane; type 3 InsP(3)R was distributed predominantly
      around the nucleus. Alterations in InsP(3)R subtype expression and localization
      may have important functions in regulating intracellular calcium release around
      the nucleus when vascular smooth muscle cells switch to a more proliferating
      phenotype.

PMID- 10891347
TI  - Expression and characterization of the N- and C-terminal ATP-binding domains of
      MRP1.
AB  - The His(6)-tagged N- and C-terminal nucleotide binding (ATP Binding Cassette,
      ABC) domains of the human multidrug resistance associated protein, MRP1, were
      expressed in bacteria in fusion to the bacterial maltose binding protein and a
      two-step affinity purification was utilized. Binding of a fluorescent ATP
      analogue occurred with micromolar dissociation constants, MgATP was able to
      inhibit the ATP-analogue binding with 70 and 200 micromolar apparent inhibition
      constants, while AMP was nearly ineffective. Both MRP1 nucleotide binding domains
      showed ATPase activities (V(max) values between 5-10 nmoles/mg protein/min),
      which is fifty to hundred times lower than that of parent transporter. The K(M)
      value of the ATP hydrolysis by the nucleotide binding domains were 1.5 mM and 1.8
      mM, which is similar to the K(M) value of the native or the purified and
      reconstituted transporter, N-ethylmaleinimide and A1F(4) inhibited the ATPase
      activity of both nucleotide binding domains.

PMID- 10891348
TI  - Characterization of human junctophilin subtype genes.
AB  - Junctophilin (JP) subtypes, namely JP-1, 2, and 3, have been currently identified
      in excitable cells and constitute a novel family of junctional membrane complex
      proteins. Our studies have suggested that JPs take part in the formation of
      junctional membrane complexes by spanning the membrane of the intracellular
      Ca(2+) store and interacting with the cell-surface membrane. In this report we
      describe the primary structures, genomic organization, and tissue distribution of
      human JP subtypes. By cloning and analyzing human genomic DNA segments, the
      protein-coding sequence interrupted with four introns was defined in each JP
      gene. The deduced human JP subtypes shared characteristic structural features
      with their rabbit and mouse counterparts. Genomic mapping demonstrated that JP
      genes do not cluster on the human genome. RNA blot hybridization indicated that
      tissue-specific expression patterns of JP genes in human are essentially the same
      as those in mouse; skeletal muscle contained both JP-1 and JP-2 mRNAs, the heart
      predominantly expressed JP-2 mRNA, and the brain specifically contained JP-3
      mRNA. In the light of this, we propose intramolecular domains of JP subtypes
      based on the structural and functional characteristics.

PMID- 10891349
TI  - In situ photoaffinity labeling of proteasome with photoactive adriamycin
      analogue.
AB  - An intracellular adriamycin (ADM)-binding protein purified from the cytosol of
      L1210 mouse lymphocytic leukemia cells had a molecular weight of 700-1500 kDa and
      hydrolyzed Suc-LLVY-MCA. When L1210 cells were incubated with a photoactive ADM
      analogue, N-(p-azidobenzoyl)-adriamycin (NAB-ADM), most of the NAB-ADM was found
      to localize in the nuclei. In situ photoaffinity labeling of L1210 cells with NAB
      ADM resulted in low protease activity in the cytosol and nuclear extracts and the
      cells showed selective photoincorporation of NAB-ADM into the proteasome. These
      results suggest that the proteasome is a translocator of ADM from the cytoplasm
      to the nucleus and might therefore become a new candidate for cancer
      chemotherapy.

PMID- 10891350
TI  - An unusual C-H...O hydrogen bond mediated reversal of polypeptide chain direction
      in a synthetic peptide helix.
AB  - An unusual C-terminal conformation has been detected in a synthetic decapeptide
      designed to analyze the stereochemistry of helix termination in polypeptides. The
      crystal structure of the decapeptide Boc-Leu-Aib-Val-Ala-Leu-Aib-Val-(D)Ala
      (D)Leu-Aib-OMe reveals a helical segment spanning residues 1-7 and helix
      termination by formation of a Schellman motif, generated by (D)Ala(8) adopting
      the left-handed helical (alpha(L)) conformation. The extended conformation at
      (D)Leu(9) results in a compact folded structure, stabilized by a potentially
      strong C-H. O hydrogen bond between Ala(4) C(alpha)H and (D)Leu(9) CO. The
      parameters for C-H. O interaction are Ala(4) C(alpha)H. O=C (D)Leu(9) distance
      3.27 A, C(alpha)-H. O angle 176 degrees, and O. H(alpha) distance 2.29 A. This
      structure suggests that insertion of contiguous D-residues may provide a handle
      for the generation of designed structures containing more than one helical
      segment folded in a compact manner.

PMID- 10891351
TI  - Effects of pH on murine insulinoma betaTC3 cells.
AB  - Confluent monolayer cultures of betaTC3 cells were exposed for 4 h to acidic,
      neutral, or alkaline pH media. Studies determined the impact of pH on viability,
      insulin secretion rate, glucose consumption rate, lactate production rate, and
      ATP content. Cell viability was not affected by exposure to media of different pH
      (>95% for all groups). Insulin release from cells exposed to acidic media (pH of
      6.4) was approximately 75% higher than that from cells exposed to either neutral
      (pH of 7.1) or alkaline (pH of 7.8) conditions. Conversely, ATP content was
      significantly reduced in cultures exposed to acidic conditions, although there
      was no statistical difference between neutral and alkaline conditions. Glucose
      consumption and lactate production rates increased linearly with increasing pH.

PMID- 10891352
TI  - Location of a cytoplasmic epitope for monoclonal antibody HK 12.18 on H,K-ATPase
      alpha subunit.
AB  - The enzyme responsible for gastric acidification is a heterodimeric (alpha and
      beta subunit) P-type ATPase, an integral protein of parietal cell apical
      membranes, which promotes electroneutral exchange of exoplasmic K(+) for
      cytoplasmic H(3)O(+). The molecular mechanisms of the catalytic exchange reaction
      are imperfectly understood, and await clarification of the precise topology of
      the enzyme with respect to the secretory membrane. Antibodies directed against
      H,K-ATPase subunits have been useful in confirming hydropathy plot predictions of
      HKalpha and HKbeta secondary structure. The monoclonal antibody HK 12.18, which
      labels gastric mucosal parietal cells by immunocytochemistry, and which binds to
      a single M(r) approximately 94,000 polypeptide by SDS-PAGE immunoblot of gastric
      microsomes, has been widely used as a specific marker of parietal cells in
      clinical and cell biological studies of acid secretion, and as a specific HKalpha
      probe in biochemical studies. However, the uncertain location of the HK 12.18
      epitope has limited the antibody's usefulness as a topology probe. In this study,
      HK 12. 18 immune reactivity with native H,K-ATPase tryptic peptides, HKalpha cDNA
      fragments expressed in bacteria, and overlapping synthetic HKalpha
      tridecapeptides, was used to identify the HK 12.18 epitope as seven consecutive
      amino acids (Asp(682)-Met-Asp-Pro-Ser-Glu-Leu(688)) in the cytoplasmic middle
      third of HKalpha.

PMID- 10891353
TI  - Caspase-dependent apoptosis in THP-1 cells exposed to oxidized low-density
      lipoproteins.
AB  - Oxidized low-density lipoproteins (oxLDL) play a critical role in atherogenesis.
      We investigated the apoptotic process in human monocytic THP-1 cell line, exposed
      to oxLDL generated by treatment of native LDL either with hypochlorous acid
      (HOCl), mainly affecting the protein moiety, or with copper sulfate (CuSO(4)),
      mainly affecting the lipid moiety. After incubation with both types of oxLDL, we
      observed: (i) microscopy signs of apoptosis in THP-1 cells, (ii) a significant
      increase of apoptotic cells proportional to LDL protein concentration, either by
      annexin V or by cell cycle phase analysis with propodium iodide flow cytometry,
      (iii) a reduction of THP-1 cell apoptosis in presence of the caspase inhibitor Z
      VAD.fmk, (iv) the resistance of THP-1 cells apoptosis after PMA-elicited
      differentiation. In conclusion, HOCl-oxLDL are as potent as Cu-oxLDL to induce
      high rates of apoptosis in monocytes through a caspase-dependent pathway.
      Moreover, the resistance of differentiated THP-1 cells to oxLDL-induced apoptosis
      is compatible with the hypothesis that mature macrophages have prolonged survival
      and thereby enhance the atherogenic process.

PMID- 10891354
TI  - Crosslinking between alpha and beta subunits defines the orientation and spatial
      relationship of some of the transmembrane helices of the proton-translocating
      pyridine nucleotide transhydrogenase of Escherichia coli.
AB  - The proton-translocating pyridine nucleotide transhydrogenase of Escherichia coli
      is composed of two types of subunits, alpha and beta, organized as an
      alpha(2)beta(2) tetramer. The protein contains three recognizable domains, of
      which domain II is the transmembrane region of the molecule containing the
      pathway for proton translocation. Domain II is composed of four transmembrane
      helices at the carboxyl-terminus of the alpha subunit and either eight or nine
      transmembrane helices at the amino-terminal region of the beta subunit. We have
      introduced pairs of cysteine residues into a cysteine-free transhydrogenase by
      site-directed mutagenesis. Disulfide bond formation between some of these
      cysteine residues occurred spontaneously or on treatment with cupric 1, 10
      phenanthrolinate. Analysis of crosslinked products confirmed that there are nine
      transmembrane helices in the domain II region of the beta subunit. The proximity
      to one another of several of the transmembrane helices was determined. Thus,
      helices 2 and 4 are close to helix 6 (nomenclature of Meuller and Rydstrom, J.
      Biol. Chem. 274, 19072-19080, 1999), and helix 3 and the carboxyl-terminal eight
      residues of the alpha subunit are close to helix 7. In the alpha(2)beta(2)
      tetramer, helices 2 and 4 of one alpha subunit are close to the same pair of
      transmembrane helices of the other alpha subunit, and helix 6 of one beta subunit
      is close to helix 6 of the other beta subunit.

PMID- 10891355
TI  - H(2)O(2)-induced tyrosine phosphorylation of protein kinase cdelta by a mechanism
      independent of inhibition of protein-tyrosine phosphatase in CHO and COS-7 cells.
AB  - It has been proposed that H(2)O(2) increases tyrosine phosphorylation of cellular
      proteins by inhibiting protein-tyrosine phosphatase through oxidation of the
      cysteine residue of the enzyme essential for its catalytic activity. Tyrosine
      phosphorylation of the delta isoform of protein kinase C (PKC) was induced by
      H(2)O(2) in CHO and COS-7 cells. H(2)O(2) also induced activation of mitogen
      activated protein kinase. Vanadate and molybdate, which inhibit protein-tyrosine
      phosphatase by binding to its active site, did not induce tyrosine
      phosphorylation of PKCdelta, but enhanced H(2)O(2)-induced tyrosine
      phosphorylation of PKCdelta in the cell. The oxoanions, however, generated the
      active form of mitogen-activated protein kinase. Another protein-tyrosine
      phosphatase inhibitor, phenylarsine oxide, which bridges the thiol residues of
      the enzyme, induced tyrosine phosphorylation of PKCdelta, and the reaction was
      enhanced by vanadate. These results suggest that inhibition of protein-tyrosine
      phosphatase is insufficient for induction of tyrosine phosphorylation of PKCdelta
      in the cells, and that presumably activation of protein-tyrosine kinase may be
      essential for tyrosine phosphorylation of the PKC isoform.

PMID- 10891356
TI  - A kinetically efficient form of the Chlamydomonas self-splicing ribosomal RNA
      precursor.
AB  - The 23S rRNA gene of Chlamydomonas reinhardtii contains a group IA3 intron,
      Cr.LSU, whose splicing is essential for cell growth. To better understand Cr.LSU
      splicing, kinetic analyses were undertaken with 23S.3, a preRNA previously shown
      to self-splice. Self-splicing of 23S.3 showed biphasic kinetics, with only
      approximately 33% reacting efficiently. Removal of a region of the 5' exon that
      could potentially interfere with the intron core (i.e., P3) increased the size
      (53%) of the active fraction. Replacement of the large P6a-extension by a 20-nt
      stem-loop further increased the active fraction to approximately 80%. The k(cat)
      and K(G)(M) for self-splicing (first step) by these latter RNAs were
      approximately 1 min(-1) and approximately 20 microM, respectively. These results
      indicate that Cr.LSU is a highly efficient ribozyme whose folding in vitro is
      impeded by exonic and/or intronic sequences. The implications for in vivo
      splicing of Cr.LSU are discussed.

PMID- 10891357
TI  - A sds22 homolog that is associated with the testis-specific serine/threonine
      protein phosphatase 1gamma2 in rat testis.
AB  - Two cDNAs sequences (1320 bp and 1180 bp) of the 55-kDa subunit associated with a
      testis-specific serine/threonine protein phosphatase 1gamma2 (PP1gamma2) were
      cloned. They were the same up to 1180 bp, suggesting that they may be generated
      by alternative splicing. Sequence studies showed that the 1320 bp-cDNA is a
      homolog of the human sds22alpha(1) (thus, named rat sds22alpha(1)). The 1180 bp
      cDNA is a new splice-variant since its sequence at the 3' end has not been
      identified in human sds22 genes (named rat sds22alpha(3)). The 1320 bp-cDNA is
      ubiquitously expressed in various tissues including the immature testis. However,
      the expression of 1180 bp-cDNA was only observed in the testis after puberty.
      This expression pattern matches very well with that of PP1gamma2, suggesting that
      1180 bp-cDNA may encode the 55-kDa subunit to associate with PP1gamma2 in rat
      testis and is involved in spermatogenesis by controlling PP1gamma2 activity.

PMID- 10891358
TI  - Metabolism of vitamin D(3) by human CYP27A1.
AB  - Human vitamin D(3) 25-hydroxylase (CYP27A1) cDNA was expressed in Escherichia
      coli, and its enzymatic properties were revealed. The reconstituted system
      containing the membrane fraction prepared from the recombinant E. coli cells was
      examined for the metabolism of vitamin D(3). Surprisingly, at least eight forms
      of metabolites including the major product 25(OH)D(3) were observed. HPLC
      analysis and mass spectrometric analysis suggested that those metabolites were
      25(OH)D(3), 26(OH)D(3), 27(OH)D(3), 24R,25(OH)(2)D(3), 1alpha, 25(OH)(2)D(3,
      )25,26(OH)(2)D(3) (25,27(OH)(2)D(3)), 27-oxo-D(3) and a dehydrogenated form of
      vitamin D(3). These results suggest that human CYP27A1 catalyzes multiple
      reactions and multiple-step metabolism toward vitamin D(3). The K(m) and V(max)
      values for vitamin D(3) 25-hydroxylation and 25(OH)D(3) 1alpha-hydroxylation were
      estimated to be 3.2 microM and 0.27 (mol/min/mol P450), and 3.5 microM and 0.021
      (mol/min/mol P450), respectively. These kinetic studies have made it possible to
      evaluate a physiological meaning of each reaction catalyzed by CYP27A1.

PMID- 10891359
TI  - Genomic organization and characterization of human PEX2 encoding a 35-kDa
      peroxisomal membrane protein.
AB  - Peroxins are proteins involved in peroxisome biogenesis and are encoded by PEX
      genes. The human PEX2 gene encodes a 35-kDa peroxisomal integral membrane protein
      which is a member of the zinc finger protein family. Mutations in the PEX2 gene
      are the primary defect in a subset of patients with Zellweger syndrome and
      related peroxisome biogenesis disorders. The role of zinc finger proteins in
      peroxisome assembly and function is poorly understood. Here we report the cloning
      and characterisation of the human PEX2 structural gene. PEX2 was assigned to
      human chromosome 8q13-q21 and its murine homologue to mouse chromosome 3. The
      gene is approximately 17.5 kb in length, and contains four exons. The entire
      coding sequence is included in one exon, exon 4. The 5'-flanking region has
      features of housekeeping genes (GC enrichment, two Sp1 sites) and tissue
      specific, inducible genes (two CCAAT boxes). In more than 1.5 kb of 5'-flanking
      sequences we did not identify consensus peroxisomal proliferator responsive
      elements (PPRE).

PMID- 10891360
TI  - Molecular cloning and characterization of a novel human gene containing ankyrin
      repeat and double BTB/POZ domain.
AB  - A novel human gene containing an ankyrin repeat and BTB/POZ domains (BPOZ) was
      isolated from a human leukocyte cDNA library. The cDNA sequence contains an open
      reading frame of 1434 bp that encodes 478 amino acid residues with a predicted
      molecular mass of 53.9 kDa. Sequence pattern analysis shows that BPOZ contains an
      N-terminal ankyrin repeat, a bipartite nuclear localization signal and two
      BTB/POZ domains. Using semiquantitative RT-PCR, the BPOZ transcript was found to
      be ubiquitously expressed in all fetal tissues examined (heart, brain, liver, and
      kidney) suggesting that BPOZ is involved in basic cellular function. Low
      expression of BPOZ in adult tissues (normal and hypertrophic heart) suggests that
      BPOZ mRNA is developmentally regulated and may play a role in developmental
      processes. Chromosomal localization by radiation hybrid mapping revealed that
      this gene is localized between D3S1269 and D3S3606 markers corresponding to the
      region of chromosome 3q21, a region frequently associated with leukemia. It is
      thus suggested that BPOZ may be functionally involved in protein-protein
      interaction, perhaps in forming protein complexes, and may have an important role
      in normal development and in the development of leukemia.

PMID- 10891361
TI  - The role of RhoA in the germinal vesicle breakdown of mouse oocytes.
AB  - We have investigated a new role of RhoA in the germinal vesicle breakdown (GVBD)
      of mouse oocytes. First, RhoA was identified by immunostaining and ADP
      ribosylation in germinal vesicle (GV) stage-oocytes. RhoA was mainly localized in
      the ooplasmic area, but rarely detected in germinal vesicle. Incubation of oocyte
      extract with C3 transferase induced a strong ADP-ribosylation at about 25 kDa.
      Incubation of GV-stage oocytes in culture medium induced the spontaneous
      maturation to GVBD by about 78 and 87% of total oocytes at 1 and 3 h,
      respectively. However, microinjection of C3 transferase into GV-stage oocytes
      significantly inhibited GVBD at 1 (GVBD = 29%) and 3 h (GVBD = 49%). To study the
      role of reactive oxygen species (ROS) in the oocyte maturation, the level of
      intra-oocyte ROS was measured using a ROS-specific fluorescent dye H(2)DCFDA
      during the oocyte maturation. Spontaneous maturation of GV-stage oocytes induced
      a significant increase of ROS at 3 h by about twofold over the control level and
      then the increased level was maintained until 6 h. However, microinjection of C3
      transferase inhibited the production of intra-oocyte ROS. Incubation with ROS
      scavengers, N-acetyl-l-cysteine and catalase, blocked the ROS increase. The ROS
      scavengers also significantly inhibited GVBD, as did C3 transferase. Thus, it was
      proposed that RhoA was involved in the GVBD, possibly by the production of ROS in
      mouse oocytes.

PMID- 10891362
TI  - Oligomerization and toxicity of beta-amyloid-42 implicated in Alzheimer's
      disease.
AB  - beta-Amyloid protein (Abeta) is the major component of senile plaques found in
      the brains of Alzheimer's patients. A novel ELISA has been developed which probes
      the early stages of oligomerization of Abeta. Incubation of Abeta solutions at 37
      degrees C and pH 7.4 produces soluble oligomers in a concentration-dependent
      manner. Fresh Abeta42 solutions rapidly form soluble oligomers, whereas Abeta40
      solutions require prolonged incubation to produce oligomers. Fresh Abeta42
      solutions are more toxic to human neuroblastoma SH-SY5Y cells than Abeta40
      solutions, possibly mediated by soluble oligomers. The differences between
      Abeta42 and Abeta40 could explain the association of the longer form with
      familial early-onset Alzheimer's disease. We also report a new strategy for solid
      phase synthesis of Abeta peptides which gives high yield and purity of the
      initial crude preparation.

PMID- 10891363
TI  - Glucocorticoid effects on NF-kappaB binding in the transcription of the ICAM-1
      gene.
AB  - Glucocorticoid hormones are potent antiinflammatory drugs. A key mechanism in the
      antiinflammatory action is repression of the nuclear factor kappa B (NF-kappaB)
      signaling pathway. This results in transcriptional repression of inflammatory
      genes controlled by NF-kappaB, including the intercellular adhesion molecule-1
      (ICAM-1). We have investigated expression levels, nuclear translocation and DNA
      binding of NF-kappaB in vitro and in vivo in U937 cells during activation and
      repression. Repression of NF-kappaB signaling by glucocorticoids does not prevent
      NF-kappaB translocation or DNA binding. However interestingly, in vivo foot
      printing of the NF-kappaB site in the ICAM-1 gene indicates that glucocorticoids
      change the conformation of the protein complex binding to the NF-kappaB site.
      These results suggests that NF-kappaB interaction with the glucocorticoid
      receptor does not displace NF-kappaB from its DNA binding site but rather changes
      the complex into a transcriptionally inert form.

PMID- 10891364
TI  - Chicken beta-globin 5'HS4 insulators function to reduce variability in transgenic
      founder mice.
AB  - Transgenic mice and rats play a vital role in the study of human diseases and the
      advancement of drug development within the pharmaceutical industry. In this
      report we describe a method which improves the yield of phenotypically desirable
      transgenic founder mice resulting from each microinjection session and
      consequently reduces animal requirements for transgenic production. We have shown
      that by flanking a tyrosinase minigene with tandem copies of the chicken beta
      globin 5'HS4 insulator there is a significant reduction in variability between
      transgenic lines, with resulting mice exhibiting similar levels of coat
      pigmentation. Furthermore, the presence of insulators leads to visually identical
      tissue distribution of pigmentation including skin, fur, eyes, points, and foot
      pads. The overall impact of insulators is to reduce the number of transgenic
      founders required in order to identity animals with an appropriate expression
      level and tissue distribution.

PMID- 10891365
TI  - Epiregulin is Up-regulated in pancreatic cancer and stimulates pancreatic cancer
      cell growth.
AB  - Epiregulin belongs to the epidermal growth factor (EGF) family of polypeptides.
      Previous studies have underscored the important role of the EGF family of ligands
      and receptors in the pathology of pancreatic ductal adenocarcinoma (PDAC) and
      chronic pancreatitis (CP). It is not known, however, whether epiregulin may also
      have a role in these diseases. Therefore, in the present study we investigated
      the expression and function of epiregulin in five pancreatic cancer cell lines
      and in PDAC and CP tissue samples. Epiregulin mRNA was present at high (MIA-PaCa
      2 cells) or moderate levels (ASPC-1, CAPAN-1, and T3M4) in most cells, but was
      below detection levels in PANC-1 cells. All the cell lines exhibited a dose
      dependent increase in growth in response to recombinant human epiregulin.
      Epiregulin mRNA levels were increased 2.1-fold in PDAC samples (P < 0.01) and 1.7
      fold in CP samples (P < 0.01), when compared with the normal controls. There was
      no correlation between epiregulin mRNA levels and tumor stage or grade. By in
      situ hybridization, a moderate to intense epiregulin mRNA signal was present in
      most pancreatic cancer cells in PDAC. In contrast, only a weak (normal pancreas)
      to moderate (CP) signals were present in the ductal and acinar cells in CP. These
      findings suggest that epiregulin may contribute to the pathobiology of PDAC, and
      may also have a role in CP.

PMID- 10891366
TI  - Adenine-induced selective apoptosis toward HIV chronically infected cells in
      vitro.
AB  - A novel strategy for anti-HIV therapy is the clearance of the residual infected
      cells from the body. Here, we show that 6-aminopurine, adenine, induced selective
      apoptosis toward HIV-1 producing chronically infected MOLT4 cells (MOLT4/HIV)
      without augmentation of virus production, whereas the growth of uninfected MOLT4
      was stimulated. This selective apoptosis did not occur with other adenine
      nucleotides or with other bases. The purine ring and the amino residue of adenine
      were responsible for the apoptosis induction and selectivity, respectively. In
      addition, adenine slightly but consistently reduced viable cell numbers and the
      production of virus in a fraction of HIV-1 chronically infected human peripheral
      blood mononuclear cells (PBMCs/HIV) at day 7. On the other hand, blastogenic
      response of normal PBMCs to PHA, PWM and Candida albicans were potentiated in the
      presence of adenine. These results indicated that the effect of adenine may be
      attributable to activation-induced selective apoptosis toward virus-infected
      cells.

PMID- 10891367
TI  - Development and comparison of two 3T3-L1 adipocyte models of insulin resistance:
      increased glucose flux vs glucosamine treatment.
AB  - Insulin resistance can be induced in vivo by intravenous infusion of glucosamine
      or in cells by incubation with glucosamine. However, a publication (Hresko, R.
      C., et al. (1998) J. Biol. Chem. 273, 20658-20668) suggests a trivial explanation
      of glucosamine-induced insulin resistance whereby intracellular ATP pools are
      depleted presumably due to the phosphorylation of glucosamine to glucosamine 6
      phosphate, a hexosamine pathway intermediate. The reduced ATP level impaired
      insulin receptor (IR) autophosphorylation and tyrosine kinase activity toward
      substrates. The present work describes the development and comparison of two
      methods for inducing insulin resistance, by treating 3T3-L1 adipocytes overnight
      using either 25 mM glucose/5 nM insulin or 2 mM glucosamine. Under these
      conditions basal glucose transport rates were comparable with controls. Insulin
      stimulated 2-deoxyglucose uptake, however, was reduced by approximately 45% in
      response to both high glucose/insulin and glucosamine treatment, relative to
      control cells. The total relative amounts of the insulin-responsive glucose
      transporter, Glut4, remained constant under both treatment conditions. The
      relative phosphotyrosine (Tyr(P)) contents of the insulin receptor and its
      substrate 1 (IRS-1) were assessed in whole cell homogenates. With both methods to
      induce insulin resistance, IR/IRS-1 Tyr(P) levels were virtually
      indistinguishable from those in control cells. Insulin-stimulated phosphorylation
      of Akt on Ser(473) was not impaired in insulin-resistant cells. Furthermore, the
      relative Tyr(P) content of the PDGF receptor was comparable in high
      glucose/insulin- or glucosamine-treated 3T3-L1 adipocytes upon subsequent
      challenge with PDGF. Finally, the relative amounts of glutamine:fructose-6
      phosphate amidotransferase and O-linked N-acetylglucosamine transferase, two
      important hexosamine pathway enzymes, were similar in both treatments when
      compared with controls. Thus, 3T3-L1 adipocytes can be used as a model system for
      studying insulin resistance induced by increased influx of glucose. Under
      appropriate experimental conditions, glucosamine treatment can mimic the effects
      of increased glucose flux without impairment of tyrosine phosphorylation-based
      signaling.

PMID- 10891369
TI  - Interaction between cytochrome P450 and other drug-metabolizing enzymes: evidence
      for an association of CYP1A1 with microsomal epoxide hydrolase and UDP
      glucuronosyltransferase.
AB  - Protein-protein interactions between cytochrome P450 (P450) and other drug
      metabolizing enzymes were studied by affinity chromatography using CYP1A1-,
      glycine-, and bovine serum albumin (BSA)-conjugated Sepharose 4B columns. Sodium
      cholate-solubilized microsomes from phenobarbital-treated rat liver were applied
      to the columns and the material eluted with buffer containing NaCl was analyzed
      by immunoblotting. Microsomal epoxide hydrolase (mEH) and UDP
      glucuronosyltransferases (UGTs), as well as NADPH-P450 reductase, were
      efficiently trapped by the CYP1A1 column. Glycine and BSA columns exhibited no
      ability to retain these proteins. Protein disulfide isomerase and calnexin, non
      drug-metabolizing enzymes expressed in the endoplasmic reticulum, were unable to
      associate with the CYP1A1 column. These results suggest that CYP1A1 interacts
      with mEH and UGT to facilitate a series of multistep drug metabolic conversions.

PMID- 10891368
TI  - A cysteine residue in the helix-loop-helix domain of Id2 is critical for
      homodimerization and function.
AB  - Id proteins are negative regulators of basic helix-loop-helix (bHLH)
      transcription factors. In this study, we compared the expression of Id2 mRNA in
      proliferating (fetal) and nonproliferating (adult) alveolar epithelial cells
      (AECs). The expression of Id2 was higher in adult AECs than in the corresponding
      fetal cells, suggesting that Id2 might play a functional role in developmental
      regulation of lung epithelial cell proliferation. By screening a mouse embryo
      cDNA library in the yeast two-hybrid system, Id2 was identified as a self
      associating protein. Structural analysis by deletion and site-directed
      mutagenesis demonstrated that the HLH domain and a cysteine residue within the
      HLH domain are essential for Id2 homodimerization. Furthermore, in vitro
      synthesized Id2 homodimers became monomers under reducing conditions, indicating
      that the formation of an intermolecular disulfide bond is critical for Id2
      homodimerization. Transient transfection assays in A549 cells showed that wild
      type Id2 down-regulated the activity of the cyclin A promoter by 70%, while
      mutating the cysteine critical for Id2 homodimerization abolished the inhibitory
      effect of wild-type Id2.

PMID- 10891370
TI  - Immunochemical identification of UGT isoforms in human small bowel and in caco-2
      cell monolayers.
AB  - Previous work had suggested the presence of significant levels of UDP
      glucuronosyltransferase 1A1 (UGT1A1) catalytic activity in human small intestinal
      microsomes, with undetectable to low UGT1A6 and 2B7 activities. To confirm the
      presence of UGT1A1 isoform in human small bowel, to explore the possible absence
      of UGT1A6 and 2B7 in the organ, and to examine induced Caco-2 cells as a
      potential model for human intestinal metabolism, Western blot analysis was
      performed using specific antibodies to the relevant UGT isoforms. Significant
      expression of UGT1A1 protein was observed in all samples of human small
      intestinal microsomes, while UGT1A6 expression was undetectable to faint and
      UGT2B7 immunoreactivity was faint to detectable. Caco-2 cells treated with
      typical enzyme-inducing agents resulted in low UGT2B7 expression but failed to
      mimic the UGT1A1 levels found in human small bowel. Further work needs to be
      performed to develop a comprehensive in vitro model for human small intestinal
      first-pass metabolism.

PMID- 10891371
TI  - Purification of dual-tagged intact recombinant proteins.
AB  - Large-scale purification of recombinant proteins has been used extensively to
      assist numerous protein studies, including investigation of function, substrate
      identification and protein-protein interaction of low abundance proteins. Genetic
      fusion of affinity tags to these proteins has also been widely used for ease of
      purification by affinity chromatography. However, this technique sometimes yields
      unstable and degraded protein products limiting its application. In this study,
      we show a facile and straightforward method of dual-tagged recombinant protein
      purification that eliminates contamination by degraded protein products. A 6His
      containing BamHI-HindIII fragment from pQE12 was ligated into the pGEX-KG BamHI
      HindIII fragment and the protein of interest (p25(nck5a), which is highly
      susceptible to proteolytic degradation when expressed and purified from bacteria)
      was cloned into the BamHI site without a termination codon. The resulting plasmid
      construct, designated as pGST-p25(nck5a)-6His, with GST at the N-terminal and
      6His at the C-terminal was expressed in Escherichia coli DH5alpha and purified
      using a two-step procedure. We show that using Ni(2+)-NTA chromatography as a
      first purification step and GSH-agarose chromatography as a second step, rather
      than vice-versa, yields a highly purified intact protein that is free of any
      contaminating degraded protein product. The purified fusion protein is soluble
      and fully active.

PMID- 10891372
TI  - Identification of functional elements in the bidirectional promoter of the mouse
      Nthl1 and Tsc2 genes.
AB  - The gene of mammalian endonuclease III homologs (NTHL1/Nthl1), a DNA
      glycosylase/AP lyase involved in base excision repair, lies immediately adjacent
      to one of the tuberous sclerosis disease-determining genes, TSC2/Tsc2, in a head
      to-head orientation. To clarify the regulation of these divergent genes, we
      studied the promoter activities of these transcription units by luciferase assay
      using HeLa cells. We found that the short spacer sequence of 63 base pairs (bp)
      between the mouse Nthl1 and Tsc2 genes shows bidirectional promoter activity
      essential for the transcription of both genes. The 63-bp sequence is well
      conserved among several mammalian species and contains two Ets-transcription
      factor binding sites (EBSs) in opposite directions. An Ets-family protein in the
      HeLa nuclear extract specifically bound to either EBSs. Mutation of the core
      motif of the EBS demonstrated that EBS positively regulates transcription of both
      mNthl1 and mTsc2 genes. These EBSs had an additive effect on transcription, and
      each EBS functioned equally in both directions.

PMID- 10891373
TI  - Increased effect of interferon gamma on PDGF-induced c-fos gene transcription in
      glomerular mesangial cells: differential effect of the transcriptional
      coactivator CBP on STAT1alpha activation.
AB  - We have previously shown that interferon gamma (IFNgamma) synergistically
      increases PDGF-induced DNA synthesis in mesangial cells. To examine the
      mechanism, we studied its effect on PDGF-induced c-fos gene transcription using a
      reporter mesangial cell in which firefly luciferase gene is driven by c-fos
      promoter. IFNgamma significantly enhanced PDGF-induced c-fos transcription. We
      have shown previously that PDGF-induced c-fos transcription in mesangial cells is
      mediated by the ternary complex factor Elk-1. Using a GAL-4 DNA binding-domain
      Elk-1 transactivation domain fusion protein-based reporter assay we showed that
      the increased effect of IFNgamma was not mediated by Elk-1 transactivation. Gel
      mobility shift assay of lysates of mesangial cells treated with a combination of
      IFNgamma and PDGF using sis-inducible DNA element (SIE) showed increased
      STAT1alpha-SIE complex formation as compared to the PDGF alone. To investigate
      the transcriptional consequences of this observation, stable reporter mesangial
      cells in which luciferase gene is driven by four copies of SIE was used. IFNgamma
      and PDGF in combination significantly increased SIE-dependent transcription as
      compared to PDGF or IFNgamma alone. Using an antibody in the gel mobility shift
      assay we showed that the PDGF-induced SIE-STAT1alpha complex recruited the
      transcriptional coactivator CBP. However, the STAT1alpha-SIE complex formed in
      the presence of IFNgamma and PDGF did not contain CBP. Taken together, our data
      provide the first evidence that the synergistic effect of IFNgamma on PDGF
      induced DNA synthesis may be the result of increased c-fos gene transcription via
      SIE. This effect occurs in the presence of increased activation of STAT1alpha
      without recruitment of the transcriptional coactivator CBP.

PMID- 10891374
TI  - Pancreatitis induces HSP72 in the lung: role of neutrophils and xanthine oxidase.
AB  - The aim of this work was to evaluate the systemic Hsp72 expression in rat lung
      and liver in vivo in a model of acute pancreatitis and investigate the possible
      involvement of xanthine oxidase and neutrophils in this process. Pancreatitis was
      induced by intraductal administration of 5% sodium taurocholate and samples of
      lung and liver were obtained 1 and 3 h later. In some groups of rats circulating
      xanthine oxidase was inhibited with oxypurinol, and neutrophil recruitment was
      blocked with a monoclonal antibody against P-selectin. Hsp72 expression was
      assessed by means of Western blot and immunohistochemistry. Results showed Hsp72
      induction in lung, but not in liver, shortly after pancreatitis. Hsp72-induced
      expression was located in bronchial epithelium, alveolar macrophages,
      infiltrating neutrophils, and blood vessels. Oxypurinol and the antibody against
      P-selectin prevented pancreatitis-induced lung Hsp72 overexpression suggesting
      that Hsp72 induction is mediated by neutrophil infiltration into the lungs.

PMID- 10891375
TI  - Familial chylomicronemia caused by a novel type of mutation in the APOE-CI-CIV
      CII gene cluster encompassing both the APOCII gene and the first APOCIV gene
      mutation: APOCII-CIV(Nijmegen).
AB  - Apolipoprotein CII (ApoCII) deficiency is a relatively rare cause of the
      chylomicronemia syndrome, a disorder characterized by severe fasting
      hypertriglyceridemia and massive accumulation of chylomicrons in plasma. Here we
      present a case which is the first example of apoCII deficiency caused by a major
      rearrangement in the APOCII gene. Southern blot analysis revealed an
      approximately 7.5-kb deletion disrupting the APOCII gene including the promotor
      region and first exon. Interestingly, the deletion also encompasses the APOCIV
      gene, a recently discovered novel gene upstream of APOCII. This deletion is the
      first mutation to be reported in the APOCIV gene.

PMID- 10891376
TI  - Structural study of the exopolysaccharide produced by a clinical isolate of
      Burkholderia cepacia.
AB  - The primary structure of the exopolysaccharide produced by a clinical isolate of
      the bacterium Burkholderia cepacia was studied by means of methylation analysis,
      selective degradation, NMR spectroscopy, and electrospray mass spectrometry. The
      resulting data showed that the parent repeating unit of the exopolysaccharide is
      a highly branched heptasaccharide with the following structure: Two acetyl groups
      are present per repeating unit, as noncarbohydrate substituents.

PMID- 10891377
TI  - Transient expression of human telomerase extends the life span of normal human
      fibroblasts.
AB  - We utilized the Cre/lox recombination system to transiently express the catalytic
      subunit of telomerase (hTERT) in normal diploid foreskin fibroblasts (BJ cells).
      A retroviral construct containing an hTERT cDNA, flanked by loxP-sites was
      introduced into near senescent BJ cells (population doubling 85). At population
      doubling (PD) 92, which exceeds the typical life span of these cells, we excised
      the gene via Cre-mediated recombination. All clones lost telomerase activity and
      showed telomere shortening over an additional 50 PDs. Interestingly, the average
      telomere length in these cells became shorter than in untreated BJ cells at
      senescence. This may be due to hTERT preferentially elongating the shortest
      telomeres, leading to greater length uniformity. In summary, transient telomerase
      expression and only a very small average telomere elongation by hTERT resulted in
      a 50% increase in life span of human fibroblasts. This suggests a potentially
      safe use of hTERT in tissue engineering.

PMID- 10891378
TI  - Dialyzable leukocyte extract suppresses the activity of essential transcription
      factors for HIV-1 gene expression in unstimulated MT-4 cells.
AB  - The human immunodeficiency virus type 1 (HIV-1) contains regulatory regions in
      its long terminal repeat (LTR) implicated in the control of viral gene
      expression. We previously demonstrated that Dialyzable Leukocyte Extract (DLE), a
      preparation derived from immune leukocytes, is able to inhibit HIV-1 replication
      in MT-4 cell cultures. Here, we examined the effect of DLE on the activation of
      NF-kappaB and Sp1 transcription factors. NF-kappaB activity was completely
      suppressed after seven days of treatment with 2.5 U/mL of DLE, with a parallel
      large reduction in the amounts of Sp1 complexes. These findings correlate with
      the maximum inhibitory effect on HIV-1 replication described in a previous
      report. IkappaBalpha and NF-kappaB p65(RelA) gene expression are not regulated by
      DLE in MT-4 cells. Although up to day, the precise molecular mechanism of DLE
      biological activity in HIV-1 infection remains unclear, this report presents data
      that indicate a potential downregulatory effect of DLE on HIV-1 gene expression.

PMID- 10891379
TI  - Human leukemic (HMC-1) mast cells are responsive to 1alpha, 25-dihydroxyvitamin
      D(3): selective promotion of ICAM-3 expression and constitutive presence of
      vitamin D(3) receptor.
AB  - Expression levels of adhesion molecules on HMC-1 mast cells were examined prior
      to and following administration of 1alpha, 25-dihydroxyvitamin D(3)
      [1,25(OH)(2)D(3)]. While most receptors (including ICAM-1) remained unchanged by
      the treatment, solely ICAM-3 expression was promoted in a dose- and time
      dependent fashion, peaking at 50 nM of 1,25(OH)(2)D(3) and 72 h, illustrating
      that like other myeloid cells, human mast cells are 1,25(OH)(2)D(3) responsive,
      yet in a highly selective manner. Flow cytometric results were confirmed by
      ELISA, by semiquantitative RT-PCR, and functionally by showing enhanced anti-ICAM
      3 mediated homotypic aggregation of 1,25(OH)(2)D(3) pretreated cells. Since
      cellular responsiveness is conferred by the vitamin D(3) receptor (VDR), we
      examined human mast cells for its expression. VDR was constitutively present in
      both HMC-1 and skin mast cells by RT-PCR technique and in nuclear extracts of HMC
      1 cells by Western blot analysis. Our data thus suggest that human mast cells are
      direct targets of 1, 25(OH)(2)D(3) action.

PMID- 10891380
TI  - Mungin, a novel cyclophilin-like antifungal protein from the mung bean.
AB  - A protein designated mungin, isolated from mung bean (Phaseolus mungo) seeds,
      possessed activity against the fungi Rhizoctonia solani, Coprinus comatus,
      Mycosphaerella arachidicola, Botrytis cinerea, and Fusarium oxysporum. The 18-kDa
      protein also possessed a novel N-terminal sequence with similarity to
      cyclophilins. It exerts an inhibitory action against alpha- and beta-glucosidases
      suppresses [(3)H]thymidine in corporation by mouse splenocytes.

PMID- 10891381
TI  - Expression of N-myristoyltransferase inhibitor protein and its relationship to c
      Src levels in human colon cancer cell lines.
AB  - Earlier, we have reported that N-myristoyltransferase (NMT) activity is higher in
      colonic epithelial neoplasms than in normal appearing colonic tissue and that
      increase in NMT activity appears at an early stage in colonic carcinogenesis
      [Magnuson, B., Raju, R. V. S., Moyana, T. N., and Sharma, R. K. (1995) J. Natl.
      Cancer Inst. 87, 1630-1635]. In this study, we demonstrate increased NMT mRNA in
      well-differentiated adenocarcinomas. NMT and c-Src mRNA levels were generally
      elevated in a subset of human colon cancer cell lines. Western blotting analysis
      employing N-myristoyltransferase inhibitory protein (NIP(71)) antibody
      demonstrated low levels of NIP(71) in high-expressing c-Src cell lines and high
      levels of NIP(71) in low-expressing c-Src cell lines. Interestingly, down
      regulation of c-Src by antisense expression in the HT-29 cell line resulted in
      increased expression of NIP(71), suggesting c-Src may negatively regulate NIP(71)
      expression. Furthermore, this is the first study demonstrating the expression of
      NIP(71) in human colon cancer cell lines and a possible relationship to colon
      carcinogenesis.

PMID- 10891382
TI  - Sequence determination and analysis of the full-length genome of colorado tick
      fever virus, the type species of genus Coltivirus (Family Reoviridae).
AB  - The Colorado tick fever virus (CTFV) is the type species of genus Coltivirus,
      family Reoviridae. Its genome consisting of 12 segments of dsRNA was completely
      sequenced. It was found to be 29,174 nucleotides long (the longest of all
      Reoviridae genomes characterized to date). Conserved sequences at the 5' end
      (SACUUUUGY) and at the 3' end (WUGCAGUS) of the 12 segments were identified. The
      analysis of the putative proteins deduced from the nucleotide sequences permitted
      to identify functional motifs. In particular, the VP1 was identified
      unambiguously as the viral RNA dependent RNA pylmerase (RDRP) (VP1pol), with a
      GDD located at a similar position to Reoviridae RDRPs. In other genes, RGD cell
      binding, NTPAse, single strand binding protein and kinase motifs were identified.
      Comparison with Reoviridae proteins showed significant similarities to RDRPs
      (CTFV-VP1) and sigma C protein of orthoreovirus (CTFV-VP6). Similarities to
      nonviral enzymatic proteins, such as methyltransferases, NTPAses, RNA replication
      factors, were also identified.

PMID- 10891383
TI  - Molecular cloning and genomic organization of an allatostatin preprohormone from
      Drosophila melanogaster.
AB  - The insect allatostatins are neurohormones, acting on the corpora allata (where
      they block the release of juvenile hormone) and on the insect gut (where they
      block smooth muscle contraction). We screened the "Drosophila Genome Project"
      database with electronic sequences corresponding to various insect allatostatins.
      This resulted in alignment with a DNA sequence coding for some Drosophila
      allatostatins (drostatins). Using PCR with oligonucleotide primers directed
      against the presumed exons of this Drosophila allatostatin gene and subsequent 3'
      and 5'-RACE, we were able to clone its cDNA. The Drosophila allatostatin
      preprohormone contains four amino acid sequences that after processing would give
      rise to four Drosophila allatostatins: Val-Glu-Arg-Tyr-Ala-Phe-Gly-Leu-NH(2)
      (drostatin-1), Leu-Pro-Val-Tyr-Asn-Phe-Gly-Leu-NH(2) (drostatin-2), Ser-Arg-Pro
      Tyr-Ser-Phe-Gly-Leu-NH(2) (drostatin-3), and Thr-Thr-Arg-Pro-Gln-Pro-Phe-Asn-Phe
      Gly-Leu-NH(2) (drostatin-4). Drostatin-2 is identical to helicostatin-2 (11-18)
      and drostatin-3 to helicostatin-3, two neurohormones previously isolated from the
      moth Helicoverpa armigera. Furthermore, drostatin-3 has previously been isolated
      from Drosophila itself. Drostatins-1 and -4 are novel members of the insect
      allatostatin neuropeptide family. The Drosophila allatostatin preprohormone gene
      contains two introns and three exons. The gene is located on the right arm of the
      third chromosome, position 96A-B. The existence of at least four different
      Drosophila allatostatins opens the possibility of a differential action of some
      of these hormones on the two recently cloned Drosophila allatostatin receptors,
      DAR-1 and -2. This is the first report on an allatostatin preprohormone from
      Drosophila.

PMID- 10891384
TI  - A new cytochrome P450 from Drosophila melanogaster, CYP4G15, expressed in the
      nervous system.
AB  - A novel cytochrome P450 was isolated from Drosophila melanogaster by PCR strategy
      with primers deduced from the crayfish Orconectes limosus CYP4C15 sequence, which
      is supposed to be involved in ecdysteroid biosynthesis. The full-length cDNA
      contains a 1980 bp open reading frame encoding a predicted protein of 574 amino
      acids and was designated CYP4G15. The corresponding gene is located at 10C1 on
      the X chromosome. The presence of a N-terminal segment mainly hydrophobic
      indicated that the corresponding enzyme is probably microsomal. In situ
      hybridization demonstrated predominant expression of CYP4G15 in the brain of
      third larval instar and Northern-blots showed no overexpression in insecticide
      resistant strain. This is the first indication of a specific P450 expressed in
      the central nervous system of Drosophila, and the putative function of the
      corresponding enzyme is discussed.

PMID- 10891385
TI  - Stabilization of chromium(V) species in bovine serum albumin adduct.
AB  - A detailed investigation of molecular interactions of the protein bovine serum
      albumin (BSA) with potassium dichromate has been made. Compelling evidence for
      the formation of a relatively stable Cr(V) species which decays only slowly to
      afford Cr(III) products has been obtained. The resulting final chromium(III)
      product mediates in cross-linking of BSA. The implications of the formation of a
      relatively stable chromium(V) as well as chromium(III)-mediated cross-links in
      the marker protein are discussed in the context of the metal ion-induced
      biotoxicity.

PMID- 10891386
TI  - The effects of thiazolidinediones on vascular smooth muscle cell activation by
      angiotensin II.
AB  - Angiotensin II (Ang II) stimulates the activation of extracellular signal
      regulated kinase (ERK), a subgroup of the mitogen-activated protein kinase (MAPK)
      family, in cultured vascular smooth muscle cells (VSMC). This ERK activation was
      recently shown to be a critical regulatory factor for Ang II-mediated migration
      and growth. It has been demonstrated that the thiazolidinedione troglitazone
      (TRO) blocked Ang II-induced DNA synthesis and migration in VSMC. Here we provide
      evidence for TRO to inhibit Ang II-induced ERK activation which was suggested to
      constitute the mechanism by which this agent blocks Ang II-induced VSMC growth
      and migration. We have found that pretreatment with PD98059, which selectively
      blocks the activity of ERK pathway at the level of MAPK kinase, decreased Ang II
      induced AP-1 activation and that TRO is capable of inhibiting Ang II-induced AP-1
      activation. On the other hand, the other thiazolidinediones pioglitazone (PIO)
      and rosiglitazone (ROSI) had little effect on Ang II-induced activation of ERK or
      AP-1, suggesting the inhibitory effects of TRO on VSMC activation by Ang II be
      independent of the peroxisome proliferator-activated receptor-gamma (PPARgamma)
      for which thiazolidinediones are ligands. Ang II-induced ERK activation was
      inhibited by protein kinase C (PKC)-specific inhibitor GF109203X, while TRO was
      also able to block PKC activator phorbol 12 myristate 13-acetate (PMA)-induced
      ERK activation. Accordingly, TRO may inhibit Ang II-induced MAPK activation at
      least partly by an inhibition of PKC. These results support the assumption that
      by targeting MAPK activation, TRO may inhibits the critical signaling steps
      leading to restenosis and atherosclerosis that may result in part from
      dysregulated VSMC growth and migration induced by Ang II.

PMID- 10891387
TI  - Exercise induces isoform-specific increase in 5'AMP-activated protein kinase
      activity in human skeletal muscle.
AB  - The 5'AMP-activated protein kinase (AMPK) is stimulated by contractile activity
      in rat skeletal muscle. AMPK has emerged as an important signaling intermediary
      in the regulation of cell metabolism being linked to exercise-induced changes in
      muscle glucose and fatty acid metabolism. In the present study, we determined the
      effects of exercise on isoform-specific AMPK activity (alpha1 and alpha2) in
      human skeletal muscle. Needle biopsies of vastus lateralis muscle were obtained
      from seven healthy subjects at rest, after 20 and 60 min of cycle ergometer
      exercise at 70% of VO(2)max, and 30 min following the 60 min exercise bout. In
      comparison to the resting state, AMPK alpha2 activity significantly increased at
      20 and 60 min of exercise, and remained at a higher level with 30 min of
      recovery. AMPK alpha1 activity tended to slightly decrease with 20 min of
      exercise at 70%VO(2)max; however, the change was not statistically significant.
      AMPK alpha1 activities were at basal levels at 60 min of exercise and 30 min of
      recovery. On a separate day, the same subjects exercised for 20 min at 50% of
      VO(2)max. Exercise at this intensity did not change alpha2 activity, and similar
      to exercise at 70% of VO(2)max, there was no significant change in alpha1
      activity. In conclusion, exercise at a higher intensity for only 20 min leads to
      increases in AMPK alpha2 activity but not alpha1 activity. These results suggest
      that the alpha2-containing AMPK complex, rather than alpha1, may be involved in
      the metabolic responses to exercise in human skeletal muscle.

PMID- 10891388
TI  - B48 is preferentially translated over B100 in cells with increased endogenous apo
      B mRNA.
AB  - We recently demonstrated that expression of BHMT in McArdle RH-7777 (McA-BHMT)
      cells increases apo B mRNA abundance, leading to parallel increases in apo B
      secretion. The ratio of unedited to edited apo B mRNA was unchanged by BHMT
      expression. Based on the observation that secretion of B48 is increased relative
      to B100 in McA-BHMT cells, current studies now include comparison of B48 and B100
      synthesis and intracellular degradation. Minor differences in co- and
      posttranslational degradation were unable to account for relative increase in B48
      secretion, and the disappearance kinetics of B48 were similar in McA-BHMT and
      control cells. Consistent with the increase in endogenous apo B mRNA in McA-BHMT
      cells, B48 synthesis is increased significantly. In contrast, synthesis of B100
      was not significantly increased. We conclude that B48 is preferentially
      translated compared to B100 when endogenous apo B mRNA is increased.

PMID- 10891389
TI  - Toll-like receptor 4-mediated signal pathway induced by Porphyromonas gingivalis
      lipopolysaccharide in human gingival fibroblasts.
AB  - The lipopolysaccharide (LPS) secreted by Porphyromonas gingivalis is implicated
      in the initiation and progression of periodontitis. Human gingival fibroblasts
      (HGFs) are the major constituent of gingival connective tissue. In this study, we
      examined the expression of Toll-like receptor 4 (TLR4) on HGFs by flow cytometric
      analysis, and studied the signal transduction induced by LPS stimulation of HGFs
      by enzyme-linked immunosorbent assay, Western blotting, and immunoprecipitation.
      We show that LPS binds to HGFs, and that HGFs express TLR4 and myeloid
      differentiation primary response gene 88 (MyD88). P. gingivalis LPS-induced
      interleukin (IL)-1 production in HGFs was inhibited by anti-TLR4 antibody. P.
      gingivalis LPS treatment of HGFs activated several intracellular proteins
      including protein tyrosine kinases, and upregulated the expression of IL-1
      receptor-associated kinase (IRAK), nuclear factor-kappaB (NF-kappaB), and
      activating protein-1 (AP-1), and these events were suppressed by anti-TLR4
      monoclonal antibody. Our findings suggest that the binding of P. gingivalis LPS
      to TLR4 on HGFs activates various second messenger systems.

PMID- 10891390
TI  - 5-Fluorouracil induces apoptosis through the suppression of NF-kappaB activity in
      human salivary gland cancer cells.
AB  - Activation of the transcription factor NF-kappaB results in protection against
      apoptosis, and the chemotherapeutic agent 5-Fluorouracil (5-FU) exerts its
      cytotoxic effect through the induction of apoptosis. Thus, we examined whether 5
      FU could induce apoptosis through the suppression of NF-kappaB activity. We found
      that upon treatment of a human salivary gland cancer cell line (cl-1) with 5-FU,
      the NF-kappaB activity was suppressed in a time-dependent manner. This inhibition
      was mediated by a prevention of the degradation of the inhibitory IkappaB-alpha
      protein. In addition, the expression of TRAF-2 and cIAP-1, which are
      transcriptionally regulated by NF-kappaB and function as anti-apoptotic molecules
      through the interruption of caspase pathway, was also inhibited by 5-FU. Finally,
      the activity of caspase-8 and caspase-3 showed a significant increase in response
      to 5-FU. By flow cytometric analysis, 5-FU did not affect the expression level of
      Fas on the cell surface. Thus, our results suggest that one of the molecular
      mechanisms involved in 5-FU-induced apoptosis in cl-1 cells may be due to the
      suppression of NF-kappaB activity, resulting in the activation of the pro
      apoptotic pathway.

PMID- 10891391
TI  - Cloning and functional expression of ATA1, a subtype of amino acid transporter A,
      from human placenta.
AB  - This report describes the primary structure and functional characteristics of
      human ATA1, a subtype of the amino acid transport system A. The human ATA1 cDNA
      was isolated from a placental cDNA library. The cDNA codes for a protein of 487
      amino acids with 11 putative transmembrane domains. The transporter mRNA (
      approximately 9.0 kb) is expressed most prominently in the placenta and heart,
      but detectable level of expression is evident in other tissues including the
      brain. When expressed heterologously in mammalian cells, the cloned transporter
      mediates Na(+)-coupled transport of the system A-specific model substrate alpha
      (methylamino)isobutyric acid. The transport process is saturable with a Michaelis
      Menten constant of 0. 89 +/- 0.12 mM. The Na(+):amino acid stoichiometry is 1:1
      as deduced from the Na(+)-activation kinetics. The transporter is specific for
      small short-chain neutral amino acids. The gene for the transporter is located on
      human chromosome 12.

PMID- 10891392
TI  - Phosphoinositide 3-kinases and the regulation of vesicular trafficking.

PMID- 10891393
TI  - Phosphorylation of eIF-4E on Ser 209 in response to mitogenic and inflammatory
      stimuli is faithfully detected by specific antibodies.
AB  - Phosphorylation of Ser 209 is thought to modulate the activity of the cap-binding
      factor eIF-4E which is a crucial component in the initiation complex for cap
      dependent translation of mRNA. We report here the full reconstitution of the p38
      Map kinase cascade leading to phosphorylation of eIF-4E in vitro and the
      generation of antibodies specific for phospho-serine 209 in eIF-4E. These
      antibodies were used to probe the phosphorylation of eIF-4E in mammalian cells
      stimulated with mitogens and pro-inflammatory cytokines. Treatment of human
      dermal fibroblasts with FCS led to a transient hyperphosphorylation, followed by
      hypophosphorylation and return to normal state phosphorylation at 16 h after the
      initial stimulation. By using a potent small molecular weight inhibitor of Mnk1,
      the upstream kinase for eIF-4E, we observed a rapid dephosphorylation of eIF-4E
      within 45 min after addition of the inhibitor, suggesting a high turnover of
      phosphate on eIF-4E mediated by Mnk1 and a yet unidentified phosphatase.

PMID- 10891394
TI  - Identification of proteassemblin, a mammalian homologue of the yeast protein,
      Ump1p, that is required for normal proteasome assembly.
AB  - We have identified a mammalian homologue of yeast Ump1p by searching for similar
      proteins in human and mouse expressed sequence tag (EST) databases. Ump1p is an
      accessory protein that is required for normal proteasome assembly in yeast (1). A
      mammalian homologue, which we refer to as "proteassemblin," is a constituent of
      proteasome assembly intermediates (preproteasomes), but not fully assembled 20S
      proteasomes, as is Ump1p in yeast. We also provide evidence that proteassemblin
      is a constituent of pre-immunoproteasomes that contain the precursor of the
      interferon-gamma-inducible subunit LMP2. By analogy with Ump1p, we hypothesize
      that proteassemblin is required for normal mammalian proteasome assembly.

PMID- 10891395
TI  - Constitutive expression and regulation of collagenase-3 in human breast cancer
      cells.
AB  - Matrix metalloproteinases (MMPs) are a family of secreted or transmembrane
      proteins that have been implicated in multiple physiological and pathological
      processes related to extracellular matrix turnover. Recent evidence strongly
      suggests a role for collagenase-3 (MMP-13) in tumor metastasis and invasion. We
      report here that collagenase-3 is constitutively expressed in the breast cancer
      cell line MDA-MB231 (MDA) and outline the molecular mechanism regulating its
      expression. Functional analysis of the collagenase-3 promoter showed that both
      the activator protein-1 (AP-1) site and the runt domain (RD) binding site were
      required for maximal constitutive expression of collagenase-3 in MDA cells.
      Determination of factors binding to those sites by Northern analysis and
      transient transfections identified the requirement of Fra-1, c-Jun, and Cbfa1 for
      basal collagenase-3 promoter activity in MDA cells.

PMID- 10891396
TI  - Molecular characterization of the mouse p47-phox (Ncf1) gene and comparative
      analysis of the mouse p47-phox (Ncf1) gene to the human NCF1 gene.
AB  - The cytosolic factor p47-phox (NCF1) is a key component of the phagocyte NADPH
      oxidase system, critical for microbicidal activity. The human p47-phox gene has
      been well characterized and resides on chromosome 7q11. Here we describe the
      molecular characterization of the mouse ortholog (Ncf1), which maps to distal
      chromosome 5, and compare the structure of the genes, commenting on the degree of
      homology. The mouse and human genes contain the same number of exons and introns,
      but the mouse gene is more compact (7.8 kb versus 15.2 kb). A percentage identity
      plot analysis comparing the human and mouse genes indicates that sequence
      homology is generally restricted to exons and does not include any large segment
      of introns or the 5' flanking sequence. The mouse gene also contains notably
      fewer repetitive elements than its human counterpart (34% versus 50%). The start
      of transcription of the mouse gene has been localized to within 12 nucleotides of
      the translation start site, similar to the human ortholog. Our findings provide
      an important foundation for investigating the evolutionary history of the p47
      phox gene, particularly as it relates to understanding the molecular basis of the
      p47-phox-deficient autosomal recessive form of chronic granulomatous disease.

PMID- 10891398
TI  - Macrophages stimulated with IFN-gamma activate NF-kappa B and induce MCP-1 gene
      expression in primary human endothelial cells.
AB  - A novel coculture model was established to study the effects of reactive oxygen
      (ROS) and reactive nitrogen species (RNS) generated by RAW 264.7 macrophages on
      NF-kappa B activation and monocyte chemoattractant protein (MCP-1) gene
      expression in primary human endothelial cells (HUVEC). This model simulates free
      radical-mediated interactions occurring in the process of cardiovascular
      diseases. The coculture of macrophages grown on filters and stimulated by IFN
      gamma-induced a pro-oxidant environment and resulted in increased DNA binding and
      NF-kappa B transactivation in HUVEC. Activation of NF-kappa B in endothelial
      cells was accompanied by an evident increase in the expression of the mRNA
      encoding for the MCP-1 protein, which stimulates the recruitment of monocytes
      into the arterial wall. Present data suggest that the influx of stimulated
      monocytes into the subendothelial space could affect redox-sensitive
      transcription factors and gene expression in the endothelium, thereby possibly
      leading to endothelial dysfunction.

PMID- 10891397
TI  - The role of reactive oxygen intermediates in the regulation of cytokine-induced
      ICAM-1 surface expression on endothelial cells.
AB  - ICAM-1 upregulation by endothelial cells plays a pivotal role in many disease
      processes, but signalling mechanisms leading to increased expression are poorly
      understood. In the current study we investigated the regulatory capacity of
      reactive oxygen intermediates (ROIs) in ICAM-1 activation by stimulating
      endothelial cells with the pro-inflammatory cytokines IL-1 beta, TNF alpha, IFN
      gamma, IL-2, and IL-4 prior to antioxidant treatment. ICAM-1 was expressed
      constitutively and upregulated on ECV304 by IL1-beta, IL2, and IFN gamma and on
      SKHEP-1 by IFN gamma, IL1-beta, and TNF alpha. Phenanthroline (PHE) and
      disulfiram (DIS) showed the greatest ability to inhibit cytokine-stimulated ICAM
      1 expression and in a dose-dependent manner. The alpha,alpha-diphenyl-beta
      picrylhydrazyl (DPPH) conversion assay showed that PHE and DIS had zero ability
      to scavenge free radicals and thus no known antioxidant activity. However, both
      are known metal chelators and our findings therefore suggest a unique role for
      metal ions in the control of cytokine-induced ICAM-1 expression on endothelial
      cells.

PMID- 10891399
TI  - A c-fos/Estrogen receptor fusion protein promotes cell cycle progression and
      proliferation of human cancer cell lines.
AB  - c-fos is the prototypic member of a family of transcription factors that regulate
      many cellular processes, including proliferation. c-fos heterodimerizes with jun
      family members to form the AP-1 transcription factor complex which binds specific
      DNA recognition elements in the promoters of many genes. Following rapid
      induction in response to serum or growth factors, c-fos regulates expression of
      downstream target genes involved in cellular proliferation. Although much work
      has focused on activation of cell cycle regulatory genes by c-fos, less is known
      about negative regulation of gene expression by this transcription factor. The
      cyclin-dependent kinase (cdk) inhibitor p21(Cip1/WAF1) is a negative regulator of
      cdk activity, thereby impeding cell cycle progression. By sequence analysis, we
      identified a putative AP-1 element in the p21(Cip1/WAF1) promoter. To investigate
      how this site regulated p21(Cip1/WAF1) expression and mitigate external effects
      on c-fos expression, we used a c-fos/estrogen receptor (c-fosER) fusion construct
      in which this transcription factor is conditionally activated by estradiol. In
      the presence of estradiol, c-fosER downregulated p21(Cip1/WAF1) promoter
      activity. This inhibition was dependent on the putative AP-1 site. Activation of
      c-fosER induced cell cycle progression and proliferation in a manner similar to
      serum stimulation. We concluded that activation of c-fosER mediated
      transcriptional inhibition of p21(Cip1/WAF1) through a previously uncharacterized
      AP-1 site, revealing an important role for c-fos in negative control of cell
      cycle regulatory genes.

PMID- 10891400
TI  - Pax4 represses pancreatic glucagon gene expression.
AB  - The paired box and homeodomain containing transcription factors Pax4 and Pax6 are
      known to be essential for development of the pancreatic endocrine cells. In this
      report we demonstrate that stable expression of Pax4 in a rat glucagon-producing
      cell line inhibits the endogenously expressed glucagon gene completely.
      Furthermore, Pax4 represses Pax6 independent transcription of the insulin
      promoter, suggesting that Pax4 can actively repress transcription in addition to
      acting by competition with the transcriptional activator Pax6.

PMID- 10891401
TI  - Synthesis of subgenomic RNAs by positive-strand RNA viruses.

PMID- 10891402
TI  - Enveloped virus is the major virus form produced during productive infection with
      the modified vaccinia virus Ankara strain.
AB  - Modified vaccinia virus Ankara (MVA) is a highly attenuated virus strain that may
      be useful as a vaccine vector. Ultrastructural examination of purified MVA showed
      that most of the viral particles are enveloped in contrast to the Copenhagen
      strain (COP). In CsCl gradients, the majority of the MVA particles displayed a
      light buoyant density characteristic of the enveloped form. Consistent with these
      results, MVA particles were poorly labeled with antibodies against the surface of
      intracellular mature virus but strongly labeled with antibodies against an
      envelope antigen. Furthermore, MVA was more resistant than the COP strain to
      neutralization by mouse anti-COP antibodies. These results suggest that the MVA
      strain may be particularly suitable for the engineering of envelope proteins and
      that MVA may be able to resist the humoral immunity displayed by previously
      vaccinated individuals.

PMID- 10891403
TI  - Lentiviral vectors pseudotyped with envelope glycoproteins derived from gibbon
      ape leukemia virus and murine leukemia virus 10A1.
AB  - Lentiviral vectors pseudotyped with the envelope glycoproteins (Env) of
      amphotropic murine leukemia virus (MLV) and the G protein of vesicular stomatitis
      virus (VSV-G) have been successfully used in recent preclinical gene therapy
      studies. We report here the generation of infectious HIV-1-derived vector
      particles pseudotyped with the Env of the molecular clone 10A1 of MLV and with
      chimeric envelope glycoprotein variants derived from gibbon ape leukemia virus
      (GaLV) and MLV. Formation of infectious HIV-1 (GaLV) pseudotype vectors was only
      possible with the substitution of the cytoplasmic tail of GaLV Env with that of
      MLV. The lentiviral vectors exhibited a host cell range identical with that of
      MLV(GaLV) and MLV(10A1) vectors, which are known to enter cells either via the
      GaLV-receptor Glvr-1 (Pit-1) or via the amphotropic receptor Ram-1 (Pit-2) in
      addition to Glvr-1, respectively. Thus, HIV-1(GaLV) and HIV-1(10A1) pseudotype
      vectors may be useful for efficient gene transfer into a variety of human tissues
      like primary human hematopoietic cells.

PMID- 10891404
TI  - Formation of immunogenic virus-like particles by inserting epitopes into surface
      exposed regions of hamster polyomavirus major capsid protein.
AB  - We generated highly immunogenic virus-like particles that are based on the capsid
      protein VP1 of the hamster polyomavirus (HaPV-VP1) and harbor inserted foreign
      epitopes. The HaPV-VP1 regions spanning amino acids 81-88 (position 1), 222/223
      (2), 244-246 (3), and 289-294 (4) were predicted to be surface exposed. An
      epitope of the pre-S1 region of the hepatitis B virus (designated S1; amino acid
      sequence DPAFR) was introduced into the predicted positions of VP1. All VP1/S1
      fusion proteins were expressed in yeast and generated virus-like particles.
      Immunoassays using the S1-specific monoclonal antibody MA18/7 and immunization of
      C57Bl6 mice with different VP1/S1 constructs showed a pronounced reactivity and a
      strong S1-specific antibody response for particles carrying the insert in
      position 1, 2, 1+2, and 1+3. Our results suggest that HaPV-VP1 represents a
      highly flexible carrier moiety for the insertion of foreign sequences offering a
      broad range of potential uses, especially in vaccine development.

PMID- 10891405
TI  - Conversion of Vibrio eltor MAK757 to classical biotype: role of phage PS166.
AB  - Temperate phage PS166 infection of Vibrio eltor MAK757 resulted in complete
      changes in all biotype-specific determinants. About 10% of the PS166 lysogens of
      MAK757 lost their eltor-specific determinants, namely, the ability to produce
      soluble hemolysin, cell-associated hemagglutinin for chicken erythrocytes, and
      resistance to polymyxin B, as well as resistance to Mukherjee's group IV phage
      and sensitivity to eltor phage e4. These lysogens were found to have acquired the
      properties of classical strains, most significantly becoming sensitive to group
      IV phage but resistant to eltor-specific e4. The remainder of these lysogens,
      however, retained their parental biotype and serotype but acquired auxotrophy for
      glycine and histidine. The differential behavior of the two types of lysogen was
      due to the integration of the phage PS166 genome at different locations in the
      host chromosome. A 800-bp BglII fragment was found to contain the attP site.
      Phage PS166 has a polyhedral head (95 nm in diameter) and a contractile tail (98
      nm in length). The phage chromosome is a linear double-stranded DNA of 110 kb and
      a G + C content of 58.7%.

PMID- 10891406
TI  - Mechanism of phage PS166-mediated biotype conversion in Vibrio cholerae: role of
      the hlyA locus.
AB  - Temperate phage PS166 lysogens of Vibrio eltor MAK757 biotype eltor belong to two
      major categories. Seventy percent of the lysogens acquire auxotrophy for glycine
      and histidine and maintain their parental biotype. About 10% of the lysogens
      become Cys(-) or Cys(-) Met(-) and are converted to the classical biotype with
      complete changes in all biotype-specific determinants. PCR and RFLP analysis
      revealed that in the latter lysogens, the phage genome integrated at the hlyA
      locus, whereas the same locus remained unaffected in lysogens that retained their
      parental biotype. These results suggest that the two types of lysogens arose due
      to integration of the phage genome at two different locations on the chromosome.
      A restriction map of the phage genome was constructed using AvaII and BglII. An
      800-bp BglII fragment carrying the attP site, located at one of the termini of
      the phage genome, was used to distinguish the two classes of lysogen.

PMID- 10891407
TI  - Neutralization and enhancement of HIV-1 infection by sera from HIV-1 infected
      individuals who progress to disease at different rates.
AB  - We examined the neutralizing/enhancing activity in sera collected at an early and
      a later time point postinfection from 13 HIV-positive nonprogressors, 13 moderate
      progressors, and 13 rapid progressors to determine the relationship between
      neutralizing/enhancing activity and disease progression. Early sera from each
      group reduced virus replication at low dilutions (10(-1) to 10(-2)) when compared
      with negative sera. The reduction was statistically significant for moderate and
      rapid progressors at 10(-1) dilution (P = 0.02 and P = 0.02 respectively) but not
      for nonprogressors (P = 0.16). Late sera from nonprogressors and moderate
      progressors reduced virus replication at low dilution but late sera from rapid
      progressors lost neutralizing activity. These data suggest that an association
      exists between neutralizing activity in sera and nonprogression or slower
      progression to disease and that loss of neutralizing activity is associated with
      disease progression. At higher dilutions (10(-3) to 10(-6)), both early and late
      sera from each group increased virus replication over negative sera. The levels
      and frequency of enhancement were higher for sera from a subgroup of
      nonprogressors than a subgroup of rapid progressors who exhibited enhancement.
      This suggests that enhancement is not associated with disease progression. The
      neutralizing/enhancing activity observed in sera of these three groups of
      subjects suggest that enhancement levels may reflect the overall level of
      antibody response to HIV. The replication patterns observed for early and late
      sera from individuals in the different groups reflect changes in antibody
      activity that appear to be associated with protection or disease progression.

PMID- 10891408
TI  - Hepatitis C virus glycoprotein E2 binding to CD81: the role of E1E2 cleavage and
      protein glycosylation in bioactivity.
AB  - The hepatitis C virus glycoproteins E1 and 2 have been expressed using
      recombinant baculoviruses following fusion to the carrier protein glutathione S
      transferase (GST). Proteins were expressed singly and as an E1E2 polyprotein with
      and without an N-terminal affinity tag. Expression of the E1E2 polyprotein, even
      when preceded by GST, led to processing in insect cells and detection of an E1E2
      complex that could be specifically purified by glutathione affinity
      chromatography. Baculovirus expressed E2 and a purified GST-E1E2 protein bound to
      the second extracellular loop of CD81 (EC2), a reported ligand for the molecule,
      but not to a truncated derivative of CD81 consisting of only the central domain
      of the loop. Purified GST-E2, however, failed to bind to CD81 suggesting a
      requirement for a free E2 amino terminus for biological activity. The binding to
      CD81 by baculovirus expressed E2 protein was comparable to that observed for E2
      derived from mammalian cells when detected by a monoclonal antibody sensitive to
      protein conformation. Furthermore, E2 protein expressed in insect cells in the
      presence of N-butyldeoxynojirimycin, an inhibitor of terminal glucose residue
      processing, formed complexes with E1 and bound to CD81-EC2 similarly to untreated
      protein. Together these data suggest that although hyperglucosylation of E2 does
      not have a major effect on bioactivity, polyprotein processing to reveal the free
      amino terminus is required.

PMID- 10891409
TI  - Protective immunity against feline immunodeficiency virus induced by inoculation
      with vif-deleted proviral DNA.
AB  - To determine whether live-attenuated feline immunodeficiency virus (FIV) proviral
      DNA will induce protective immunity, a plasmid clone constructed with a FIV
      provirus containing a deletion in the viral accessory gene vif (FIV-pPPR
      Deltavif) was inoculated as proviral DNA into four cats by the intramuscular
      route. After 43 weeks, these cats were boosted with the same proviral plasmid.
      Analysis of peripheral blood mononuclear cells at several time points after the
      primary and booster inoculations revealed no detectable virus or proviral DNA. At
      6 weeks after the booster, immunized cats and additional naive control cats were
      challenged with a cell-free preparation of the infectious biological isolate FIV
      PPR by the intraperitoneal route. Virus was detected after challenge in
      unvaccinated control cats but not in any of the FIV-pPPR-Deltavif-immunized cats.
      Both FIV Gag- and Env-specific cytotoxic T lymphocyte (CTL) activities were
      detected in peripheral blood cells of control cats after challenge infection,
      whereas only one of four cats immunized with FIV-pPPR-Deltavif DNA exhibited a
      measurable CTL response to Env following challenge. Although anti-Gag antibodies
      were not detected after both proviral DNA inoculation and challenge, anti-Env
      antibodies were found in FIV-pPPR-Deltavif-immunized cats after vaccination as
      well as after challenge. These findings indicate that inoculation with FIV-pPPR
      Deltavif proviral DNA induced resistance to challenge with infectious FIV and
      that a vif deletion mutant may provide a relatively safe attenuated lentiviral
      vaccine.

PMID- 10891410
TI  - Impaired entry of soluble receptor-resistant mutants of mouse hepatitis virus
      into cells expressing MHVR2 receptor.
AB  - Mouse hepatitis virus (MHV) JHMV and its soluble receptor-resistant (srr)
      mutants, srr7, srr11, and srr18, grew and induced syncytia equally well in BHK-R1
      cells expressing the MHVR1 receptor derived from MHV-susceptible BALB/c mice. In
      contrast, srr growth and syncytia formations were drastically reduced relative to
      wild-type (wt) virus in BHK-R2 cells expressing the MHVR2 receptor from MHV
      resistant SJL mice. Infections by these srr mutants in BHK-R2 cells were 0.7 to
      1.5 log10 less efficient than those of wt virus. BHK cells expressing both MHVR1
      and MHVR2 supported srr replication to the same extent as did BHK-R1 cells,
      suggesting that inefficient infection by srr mutants in BHK-R2 cells resulted
      from the absence of the effective receptor MHVR1. Virus-receptor binding tests
      failed to demonstrate a difference between the abilities of wt and srr18 to bind
      MHVR2. The binding of srr7 and srr11 to both MHVR1 and MHVR2 was revealed lower
      by two- to fourfold relative to the wt binding. The fusion activity of srr S
      proteins as examined by the expression with recombinant vaccinia virus was
      apparently lower than that of the wt S protein in BHK-R2 cells, while there was
      not such a remarkable difference in BHK-R1 cells. This suggests that the most
      likely reason for inefficient infection by mutants in BHK-R2 is impaired virus
      entry into cells. These observations suggest that inefficient infections in BHK
      R2 cells by srr mutants occur in the absence of a functional receptor MHVR1,
      which plays an important role in srr entry into cells.

PMID- 10891411
TI  - Mutational analysis of the putative receptor-binding domain of Moloney murine
      leukemia virus glycoprotein gp70.
AB  - The entry of Moloney murine leukemia virus (MoMuLV) to murine cells is mediated
      by the binding of its envelope glycoprotein gp70 to its receptor, the cationic
      amino acid transporter MCAT-1. The binding property of the envelope protein lies
      mainly in the N-terminal half of the protein. To identify essential residues
      involved in the binding of gp70 to its receptor, we have mutated amino acids
      within the putative receptor-binding domain of MoMuLV gp70. Changes in the
      residues P94 and W100 resulted in lower viral titers in comparison to the wild
      type virions. Single, double, or triple point mutations involving the residue
      W100 make the envelope protein severely defective in binding to its receptor.
      Binding studies and cell fusion experiments with murine XC cells suggested that
      the residue W100 might play an important role in the process of infection by
      making contact between gp70 and its receptor.

PMID- 10891412
TI  - Characterization of the DNA replication module of bacteriophage A2 and use of its
      origin of replication as a defense against infection during milk fermentation by
      Lactobacillus casei.
AB  - Adjacent to the lysis/lysogeny cassette of the A2 phage genome lies a stretch of
      over 8 kb, which contains a series of genes probably involved in DNA replication.
      Fifteen open reading frames (orfs) were identified, 13 of which are encoded on
      the main coding strand and only two on the complementary strand. Database
      searches and comparative analyses allowed the identification of an open reading
      frame (orf455) that shows similarity with DNA helicases and contains a variant
      zinc-finger motif known from the phage T7 helicase/primase. Orf770 showed
      similarity to putative plasmid and phage DNA primases. Downstream of orf770 is a
      noncoding 258-bp region rich in direct and inverted repeats, which specifically
      binds to proteins whose synthesis is induced during phage infection. When present
      in a plasmid, this region can direct a partial bacteriophage resistance phenotype
      due to interference with phage DNA replication, both under laboratory conditions
      and during milk fermentation. It is deduced that this stretch contains the origin
      of replication of phage A2.

PMID- 10891413
TI  - Human immunodeficiency virus type 1 Nef epitopes recognized in HLA-A2 transgenic
      mice in response to DNA and peptide immunization.
AB  - We investigated the immune response against a human immunodeficiency virus type 1
      (HIV-1) nef DNA sequence administered epidermally in mice transgenic for the
      human major histocompatibility complex (MHC) class I molecule HLA-A201. Ten
      potential HLA-A2 binding 9-mer Nef peptides were identified by a computer-based
      search algorithm. By a cell surface MHC class I stabilization assay, four
      peptides were scored as good binders, whereas two peptides bound weakly to HLA
      A2. After DNA immunization, cytotoxic T lymphocyte (CTL) responses were
      predominantly directed against the Nef 44-52, 81-89, and 85-93 peptides.
      Interestingly, the 44-52 epitope resides outside the regions of Nef where
      previously described CTL epitopes are clustered. Dominance among Nef-derived
      peptides did not strictly correlate with HLA-A2 binding, in that only one of the
      high-affinity binding peptides was targeted in the CTL response. The 44-52, 85
      93, and 139-147 peptides also generated specific CTLs in response to peptide
      immunization. T helper cell proliferation was detected after stimulation with 20
      mer peptides in vitro. Three Nef regions (16-35, 106-125, and 166-185) dominated
      the T helper cell proliferation. The implications of these results for the
      development of DNA-based vaccines against HIV is discussed.

PMID- 10891414
TI  - Induction of hepatitis C virus-specific cytotoxic T lymphocytes in mice by an
      intrahepatic inoculation with an expression plasmid.
AB  - We assessed the possibility of intrahepatic inoculation with a plasmid encoding
      hepatitis C virus (HCV) proteins to elicit HCV-specific cytotoxic T lymphocytes
      (CTL) in mice as a conventional animal model of HCV infection. BALB/c mice were
      intrahepatically or intramuscularly inoculated with an expression plasmid DNA
      encoding HCV structural proteins under the control of the elongation factor 1
      alpha promoter. Expressions of HCV-core protein and envelope proteins (E1 and E2)
      in hepatocytes were detected immunohistochemically 6 days after inoculation. CTL
      responses were examined using target cells either pulsed with a specific peptide
      or infected with a recombinant vaccinia virus expressing HCV structural protein.
      Both intrahepatically and intramuscularly DNA-inoculated mice developed CD8(+),
      MHC class I-restricted CTL responses that recognized the peptide pulsed as well
      as HCV proteins expressing target cells. These studies demonstrated the
      usefulness of a murine model of HCV infection induced by direct intrahepatic DNA
      inoculation for understanding the immunopathogenic mechanisms in HCV infection.

PMID- 10891415
TI  - Identification and characterization of a 30K protein (Ad4E3-30K) encoded by the
      E3 region of human adenovirus type 4.
AB  - Human adenovirus type 4 (Ad4), the sole member of subgroup E, contains an open
      reading frame in the E3 region predicted to encode a unique 30-kDa protein (named
      Ad4E3-30K). Ad4E3-30K is predicted to be an integral membrane protein containing
      an N-terminal signal sequence, a lumenal domain, a transmembrane domain near the
      C-terminus, and a 37-amino-acid cytoplasmic tail. To determine whether this
      protein is expressed, rabbit polyclonal antisera were raised against 30K
      containing fusion proteins expressed in bacteria. A 30K protein was detected by
      immunoprecipitation from cell-free translation products and from Ad4-infected
      A549 cells radiolabeled in the presence of tunicamycin. The protein was detected
      at only low levels in infected cells. It was not synthesized by a mutant with a
      large E3 deletion that includes the Ad4E3-30K gene. This mutant grows as well as
      wild-type Ad4 in culture. Features of Ad4E3-30K were characterized in different
      transient expression systems. The protein underwent glycosylation by addition of
      approximately six asparagine-linked oligosaccharides. These glycans were
      sensitive to endoglycosidase H, indicating that they were either high-mannose or
      hybrid types, but not complex types, and that the protein did not pass through
      the Golgi apparatus. Immunofluorescence staining of transfected cells revealed
      that Ad4E3-30K was localized primarily in the endoplasmic reticulum and nuclear
      envelope.

PMID- 10891416
TI  - The catalytic subunit of herpes simplex virus type 1 DNA polymerase contains a
      nuclear localization signal in the UL42-binding region.
AB  - The herpes simplex virus type 1 DNA polymerase consists of a catalytic subunit
      (POL or UL30) and a processivity factor (UL42). The POL/UL42 interaction, which
      occurs through the extreme C-terminus of POL, is essential for HSV-1 replication
      and thus represents a valid target for drug inhibition. We recently showed (A.
      Loregian et al. (1999) Proc. Natl. Acad. Sci. USA 96, 5221-5226) that an
      oligopeptide corresponding to the 27 C-terminal amino acids of POL, when
      delivered into herpes simplex virus type 1-infected cells by a protein carrier,
      was able to localize into the nucleus and to inhibit viral replication by
      disruption of the POL/UL42 interaction. In this report, to further characterize
      the 27 mer (Pol peptide), we investigated whether its nuclear localization was
      due to the presence of a nuclear localization signal. By testing the ability of
      the Pol peptide to localize the beta-galactosidase, a normally cytoplasmic
      protein, to the nucleus, we confirmed that the Pol peptide contained a functional
      nuclear localization signal, corresponding to the RRMLHR motif. This sequence
      proved not only necessary but also sufficient for nuclear localization, because
      its substitution with a six-alanine stretch prevented nuclear translocation of
      the beta-galactosidase-Pol peptide fusion. Site-directed mutagenesis experiments
      on this revealed that both the three basic arginines and the two hydrophobic
      residues Met and Leu were crucial for nuclear targeting. Finally, functionally
      equivalent sequences were also found in the C-terminus of the catalytic subunits
      of human cytomegalovirus (RRLHL) and of equine herpesvirus-1 DNA polymerase
      (RRILH).

PMID- 10891417
TI  - H-2(d) mice born to and reared by HBeAg-transgenic mothers do not develop T cell
      tolerance toward the hepatitis B virus core gene products.
AB  - The function of the secretory core gene product (HBeAg) of the human hepatitis B
      virus (HBV) is unknown. It has been proposed that this protein may be passed from
      the mother to her offspring at the perinatal stage where it might induce immune
      tolerance. In a previous study we have shown that the murine placenta presents an
      efficient barrier for the HBe protein and that H-2(b) mice born to HBeAg-positive
      transgenic mothers do not develop tolerance of specific cytotoxic T cells. In the
      present work we demonstrate that transgenic mice expressing high serum levels of
      HBeAg secrete only small amounts of this protein into their milk and excrete
      minute amounts of the viral gene product in their urine. Furthermore, it is shown
      that nontransgenic H-2(d) mice born to and reared by HBeAg-positive mothers
      exhibit a reactivity of HBc/eAg-specific CD4(+) Th cells and CD8(+) cytotoxic T
      cells comparable to that of normal isogenic control mice. In accordance with this
      observation the humoral immune responses directed against the HBeAg were
      comparable between these two groups of animals. This finding indicates that H
      2(d) mice potentially exposed to small amounts of maternal HBeAg transferred by
      the transplacental, lactogenic, or renal route do not develop tolerance toward
      the HBV core gene products. These data challenge the hypothesis that a potential
      function of the HBeAg may be to operate as a tolerogen at the perinatal
      developmental stage.

PMID- 10891418
TI  - Characterization of a monoclonal antibody directed to the surface of MA104 cells
      that blocks the infectivity of rotaviruses.
AB  - Rhesus rotavirus (RRV) binds to sialic acid residues on the surface of target
      cells, and treatment of these cells with neuraminidase greatly reduces virus
      binding with the consequent reduction of infectivity. Variants that can
      efficiently infect neuraminidase-treated cells have been isolated, indicating
      that attachment to sialic acid is not an essential step for animal rotaviruses to
      infect cells. To identify and characterize the neuraminidase-resistant receptor
      for rotaviruses, we have isolated a hybridoma that secrets a monoclonal antibody
      (MAb) (2D9) that specifically blocks the infectivity of wild-type (wt) RRV and of
      its sialic acid-independent variant nar3, in untreated as well as in
      neuraminidase-treated cells. The infectivity of a human rotavirus was also
      inhibited, although to a lesser extent. MAb 2D9 blocks the binding of the variant
      to MA104 cells, while not affecting the binding of wt RRV; in addition, this MAb
      blocked the attachment of a recombinant glutathione S-transferase (GST)-VP5
      fusion protein, but did not affect the binding of GST-VP8. Altogether these
      results suggest that MAb 2D9 is directed to the neuraminidase-resistant receptor.
      This receptor seems to mediate the direct attachment of the variant to the cell,
      through VP5, while the receptor is used by wt RRV for a secondary interaction,
      after its initial binding to sialic acid, through VP8. MAb 2D9 interacts
      specifically with the cell surface by indirect immunofluorescence, immunoelectron
      microscopy, and FACS. By a solid-phase immunoisolation technique, MAb 2D9 was
      found to react with three proteins of ca. 47, 55, and 220 kDa, which might form a
      complex.

PMID- 10891419
TI  - An anti-human immunodeficiency virus multiple antigen peptide encompassing the
      cleavage region of the env precursor interferes with membrane fusion at a post
      CD4 binding step.
AB  - CLIV is a multiple antigen peptide ([PTKAKRRVVQREKR](4)-K(2)-K-betaA) that
      encompasses the cleavage region of the human immunodeficiency virus type 1 (HIV
      1) envelope precursor. It displays an antiviral activity against HIV-1 and HIV-2
      and inhibits HIV-1 Env-mediated cell-to-cell fusion. This effect has previously
      been attributed to interference with Env processing, resulting in the expression
      of a nonfusogenic envelope [Virology (1998) 247, 137]. However, we show here that
      CLIV does not alter the status of Env cleavage at steady state. Using various
      aggregation/syncytium assays that allow us to discriminate between gp120/CD4
      binding and binding followed by gp41-mediated fusion, we demonstrate that CLIV
      inhibits a step of the cell-to-cell fusion process after CD4 binding. We
      demonstrate also that CLIV binds at 37 degrees C to a single class of protein
      present at the CD4(+) cell surface (Scatchard analysis: K(d) = 8 nM; B(max) =
      10(4) sites/cell) and that the fusion inhibition activity seems to correlate with
      binding to this proteic component. In contrast, CLIV interacts with neither
      membrane-inserted nor CD4-associated Env. We therefore propose that CLIV
      interferes after Env/CD4 binding with a step of the membrane fusion process that
      may involve the C-terminal domain of gp120.

PMID- 10891420
TI  - Relationship of oligomerization to DNA binding of Wheat dwarf virus RepA and Rep
      proteins.
AB  - Members of the genus Mastrevirus (family Geminiviridae) produce a complementary
      sense (c-sense) transcription unit with the potential to encode two proteins,
      RepA and Rep. In the present work, we have studied the DNA-protein complexes
      formed by the Wheat dwarf virus (WDV) RepA protein within the WDV large
      intergenic region. WDV RepA forms large nucleoprotein complexes near the TATA
      boxes of the viral complementary-sense and virion-sense (v-sense) promoters (the
      RepA C- and V-complexes, respectively), a location similar to those of WDV Rep
      DNA complexes but with distinct DNase I footprints. We have also studied the
      relationship of oligomerization of WDV RepA and Rep proteins to DNA-protein
      complex formation. Using chemical cross-linking, we have determined that both WDV
      proteins can form oligomers in solution. Interestingly, the pH is critical for
      the monomer-oligomer equilibrium and small changes produce a displacement in such
      a way that at pH </= 7.0, the predominant species is an octamer while at pH >/=
      7.4 it is a monomer. Complex formation is also strongly affected by pH and occurs
      more efficiently at pH 7.0-7.4. We found that preformed oligomers interact very
      poorly with DNA. Thus, our data are consistent with a stepwise model for protein
      DNA complex assembly in which monomers interact with DNA and then with other
      monomers to assemble an oligomeric structure on the DNA. These results may be
      relevant for studies on the DNA binding, replication, and transcription
      properties of geminivirus proteins.

PMID- 10891421
TI  - Infectious cDNA clone of the RA27/3 vaccine strain of Rubella virus.
AB  - Rubella virus (RUB), a small plus-strand RNA virus, is a significant human
      pathogen. The RA27/3 vaccine strain of RUB is one of the most successful live
      attenuated vaccines developed. In this article, we report the construction of an
      RA27/3 infectious clone, a complete cDNA copy of the RA27/3 genome that can be
      transcribed in vitro to generate infectious RNA molecules. Virus generated from
      such in vitro transcripts was phenotypically similar to RA27/3 virus. To
      investigate the attenuation of the RA27/3 strain, a series of chimeras was made
      by the insertion of different fragments of the RA27/3 genome into an infectious
      clone based on the Therien wild-type strain of RUB. Analysis of the resulting
      chimeric viruses revealed that the pattern of RA27/3 attenuation in cell culture
      is complex: attenuating elements in the RA27/3 genome were found in the 5'
      untranslated region (UTR), a region of the nonstructural proteins containing the
      protease motif and the capsid gene. Within the 5' UTR, the attenuation
      determinant was mapped to nt 7. Surprisingly, these analyses also revealed a
      potentiating mutation at nt 164 of the RA27/3 genome. Although this determinant
      was within the coding sequences of the nonstructural proteins, the encoded amino
      acid had no effect on cell culture phenotype and thus the determinant may operate
      at the level of RNA structure. In addition to investigation of the mechanisms of
      RA27/3 attenuation, the availability of the RA27/3 infectious clone offers the
      opportunity for strict genetic control over RUB vaccine manufacturing, for
      development of novel DNA-based vaccines against RUB, and for development of
      recombinant RUB vaccines that also target other diseases.

PMID- 10891422
TI  - Full-length tobacco mosaic virus RNAs and defective RNAs have different 3'
      replication signals.
AB  - The viral replicase complex of positive-stranded RNA viruses interacts with cis
      acting elements that are usually located at the termini of the viral RNAs. On
      comparison of the replication requirement of a tobacco mosaic virus (TMV)-based
      defective RNA (dRNA) and its helper virus, we found different requirements for
      replication of TMV RNAs in cis and in trans. The level of replication of full
      length TMV RNA decreased substantially in the absence of pseudoknot (pk) 1 and/or
      2, whereas identical deletions in dRNAs did not affect their replication.
      However, pk3 was required for replication of both full-length TMV RNAs and dRNAs.
      The requirements for homologous sequences were greater for dRNA replication than
      for replication of full-length TMV RNAs. Defective RNAs with heterologous 3'
      nontranslated regions (NTRs) failed to be replicated or replicated minimally,
      whereas replication of similarly mutated full-length RNAs was much less affected.
      Increasing amounts of contiguous heterologous sequences in the dRNAs compensated
      for the impaired interactions between the replicase and 3' NTR. The precision
      requirement appeared to involve the terminal 28 nucleotides, specifically the
      pseudoknot in the aminoacyl acceptor arm of the tRNA like structure, which was
      important in replication of both dRNAs and full-length TMV RNAs.

PMID- 10891423
TI  - Recombinant respiratory syncytial viruses with deletions in the NS1, NS2, SH, and
      M2-2 genes are attenuated in vitro and in vivo.
AB  - Respiratory syncytial virus (RSV) encodes several proteins that lack well-defined
      functions; these include NS1, NS2, SH, and M2-2. Previous work has demonstrated
      that NS2, SH, and M2-2 can each be deleted from RSV genome and thus are
      considered as accessory proteins. To determine whether RSV can replicate
      efficiently when two or more transcriptional units are deleted, we removed NS1,
      NS2, SH, and M2-2 genes individually and in different combinations from an
      infectious cDNA clone derived from human RSV A2 strain. The following six mutants
      with two or more genes deleted were obtained: DeltaNS1NS2, DeltaM2-2SH, DeltaM2
      2NS2, DeltaSHNS1, DeltaSHNS2, and DeltaSHNS1NS2. Deletion of M2-2 together with
      NS1 was detrimental to RSV replication. It was not possible to obtain a
      recombinant RSV when all four genes were deleted. All of the double and triple
      deletion mutants exhibited reduced replication and small plaque morphology in
      vitro. Replication of these deletion mutants was more reduced in HEp-2 cells than
      in Vero cells. Among the 10 single and multiple gene deletion mutants obtained,
      DeltaM2-2NS2 was most attenuated. DeltaM2-2NS2 formed barely visible plaques in
      HEp-2 cells and had a reduction of titer of 3 log(10) compared with the wild-type
      recombinant RSV in infected HEp-2 cells. When inoculated intranasally into cotton
      rats, all of the deletion mutants were attenuated in the respiratory tract. Our
      data indicated that the NS1, NS2, SH, and M2-2 proteins, although dispensable for
      virus replication in vitro, provide auxiliary functions for efficient RSV
      replication.

PMID- 10891424
TI  - Many multipotential gene-marked progenitor or stem cell clones contribute to
      hematopoiesis in nonhuman primates.
AB  - Retroviral insertion site analysis was used to track the contribution of
      retrovirally transduced primitive progenitors to hematopoiesis after autologous
      transplantation in the rhesus macaque model. CD34-enriched mobilized peripheral
      blood cells were transduced with retroviral marking vectors containing the neo
      gene and were reinfused after total body irradiation. High-level gene transfer
      efficiency allowed insertion site analysis of individual myeloid and erythroid
      colony-forming units (CFU) and of highly purified B- and T-lymphoid populations
      in 2 animals. At multiple time points up to 1 year after transplantation,
      retroviral insertion sites were identified by performing inverse polymerase chain
      reaction and sequencing vector-containing CFU or more than 99% pure T- and B-cell
      populations. Forty-eight unique insertion sequences were detected in the first
      animal and also in the second animal, and multiple clones contributed to
      hematopoiesis at 2 or more time points. Multipotential clones contributing to
      myeloid and lymphoid lineages were identified. These results support the concept
      that hematopoiesis in large animals is polyclonal and that individual
      multipotential stem or progenitor cells can contribute to hematopoiesis for
      prolonged periods. Gene transfer to long-lived, multipotent clones is shown and
      is encouraging for human gene therapy applications.

PMID- 10891425
TI  - Fates of human B-cell precursors.
AB  - Development of mammalian B-lineage cells is characterized by progression through
      a series of checkpoints defined primarily by rearrangement and expression of
      immunoglobulin genes. Progression through these checkpoints is also influenced by
      stromal cells in the microenvironment of the primary tissues wherein B-cell
      development occurs, ie, fetal liver and bone marrow and adult bone marrow. This
      review focuses on the developmental biology of human bone marrow B-lineage cells,
      including perturbations that contribute to the origin and evolution of B-lineage
      acute lymphoblastic leukemia and primary immunodeficiency diseases characterized
      by agammaglobulinemia. Recently described in vitro and in vivo models that
      support development and expansion of human B-lineage cells through multiple
      checkpoints provide new tools for identifying the bone marrow stromal cell
      derived molecules necessary for survival and proliferation. Mutations in genes
      encoding subunits of the pre-B cell receptor and molecules involved in pre-B cell
      receptor signaling culminate in X-linked and non-X-linked agammaglobulinemia. A
      cardinal feature of these immunodeficiencies is an apparent apoptotic sensitivity
      of B-lineage cells at the pro-B to pre-B transition. On the other end of the
      spectrum is the apoptotic resistance that accompanies the development of B
      lineage acute lymphoblastic leukemia, potentially a reflection of genetic
      abnormalities that subvert normal apoptotic programs. The triad of laboratory
      models that mimic the bone marrow microenvironment, immunodeficiency diseases
      with specific defects in B-cell development, and B-lineage acute lymphoblastic
      leukemia can now be integrated to deepen our understanding of human B-cell
      development.

PMID- 10891426
TI  - Biological and therapeutic aspects of infant leukemia.

PMID- 10891427
TI  - Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1
      in angiogenesis and tumor progression.
AB  - Although several CXC chemokines have been shown to induce angiogenesis and play
      roles in tumor growth, to date, no member of the CC chemokine family has been
      reported to play a direct role in angiogenesis. Here we report that the CC
      chemokine, monocyte chemotactic protein 1 (MCP-1), induced chemotaxis of human
      endothelial cells at nanomolar concentrations. This chemotactic response was
      inhibited by a monoclonal antibody to MCP-1. MCP-1 also induced the formation of
      blood vessels in vivo as assessed by the chick chorioallantoic membrane and the
      matrigel plug assays. As expected, the angiogenic response induced by MCP-1 was
      accompanied by an inflammatory response. With the use of a rat aortic sprouting
      assay in the absence of leukocytic infiltrates, we ruled out the possibility that
      the angiogenic effect of MCP-1 depended on leukocyte products. Moreover, the
      direct effect of MCP-1 on angiogenesis was consistent with the expression of
      CCR2, the receptor for MCP-1, on endothelial cells. Assessment of supernatant
      from a human breast carcinoma cell line demonstrated the production of MCP-1.
      Treatment of immunodeficient mice bearing human breast carcinoma cells with a
      neutralizing antibody to MCP-1 resulted in significant increases in survival and
      inhibition of the growth of lung micrometastases. Taken together, our data
      indicate that MCP-1 can act as a direct mediator of angiogenesis. As a chemokine
      that is abundantly produced by some tumors, it can also directly contribute to
      tumor progression. Therefore, therapy employing antagonists of MCP-1 in
      combination with other inhibitors of angiogenesis may achieve more comprehensive
      inhibition of tumor growth.

PMID- 10891428
TI  - Expression and coreceptor activity of STRL33/Bonzo on primary peripheral blood
      lymphocytes.
AB  - CCR5 and CXCR4 are the major coreceptors that mediate human immunodeficiency
      virus 1 (HIV-1) infection, while most simian immunodeficiency virus (SIV)
      isolates use CCR5. A number of alternative coreceptors can also mediate infection
      of some virus strains in vitro, although little is known about their in vivo
      relevance. Therefore, we characterized the expression pattern and coreceptor
      activity of one of these alternative coreceptors, STRL33/Bonzo, using a newly
      developed monoclonal antibody. In addition to being highly expressed
      (approximately 1000-7000 STRL33 ABS [antibody binding sites]) on specific subsets
      of natural killer cells (CD3(-)/CD16(-/low)/CD56(+) and CD3(-)/CD16(low)/CD56(-))
      and CD19(+) B lymphocytes (approximately 300-5000 STRL33 ABS), STRL33 was
      expressed at levels sufficient to support virus infection on freshly isolated,
      truly naive CD4(+)/CD45RA(+)/CD62L(+) cells (6000-11 000 ABS). STRL33 expression
      on peripheral blood mononuclear cells (PBMCs) was increased by mitogenic
      stimulation (OKT3/IL-2 [interleukin-2] had a greater effect than
      phytohemaglutinin (PHA)/IL-2), but it was dramatically decreased upon Ficoll
      purification. Infection of CCR5(-) human peripheral blood lymphocytes (PBLs)
      showed that 2 different SIV envelope (Env) proteins mediated entry into STRL33(+)
      cells. More importantly, the preferential infection of STRL33(+) cells in CCR5(-)
      PBLs by an R5/X4/STRL33 HIV-1 maternal isolate in the presence of a potent CXCR4
      antagonist (AMD3100) suggests that STRL33 can be used as a coreceptor by HIV-1 on
      primary cells. Rhesus macaque (rh) STRL33 was used less efficiently than human
      STRL33 by the majority of SIV Env proteins tested despite similar levels of
      expression, thereby making it less likely that STRL33 is a relevant coreceptor in
      the rhesus macaque system. In summary, the expression pattern and coreceptor
      activity of STRL33 suggest its involvement in trafficking of tumor-infiltrating
      lymphocytes and indicate that STRL33 may be a relevant coreceptor in vivo.

PMID- 10891430
TI  - Langerhans cell deficiency in reticular dysgenesis.
AB  - Reticular dysgenesis is a rare inherited immunodeficiency characterized by the
      lack of blood monocytes and neutrophils and low lymphocyte counts, contrasting
      with normal red blood cell counts and normal or decreased platelet counts.
      Whether dendritic cells or macrophages, both of which derive primarily from blood
      monocytes, are affected in this condition remains unknown. We studied 7 patients
      with reticular dysgenesis. Macrophages were present in normal numbers in the
      dermis and in the atrophic lymphoid tissues of these patients, proving that at
      least some subsets of macrophages can differentiate despite very low monocyte
      counts. By contrast, Langerhans cells, which are CD1a-positive epidermal
      dendritic cells, were absent in all (n = 5) patients before bone marrow
      transplantation. After bone marrow transplantation, Langerhans cells were present
      (n = 2), suggesting that the defect is not related to keratinocyte dysfunction. A
      split chimeric reconstitution, characterized by the presence of autologous blood
      monocytes able to differentiate in vitro into CD1a-positive dendritic cells, was
      observed in a patient who underwent successful engraftment. These results suggest
      that an intrinsic cell defect is unlikely and that a bone marrow-derived factor
      may be defective in reticular dysgenesis; it may be responsible for the
      Langerhans cell defect but not involved in macrophage differentiation.

PMID- 10891429
TI  - Stromal cell-derived factor-1 and macrophage-derived chemokine: 2 chemokines that
      activate platelets.
AB  - Platelets play roles in both thrombosis and inflammation, and chemokines that are
      released at sites of inflammation could potentially activate platelets. Among the
      chemokine receptors expressed on platelets, the CXCR4 is the receptor for
      chemokine stromal cell-derived factor-1 (SDF-1), and the CCR4 is the receptor for
      macrophage-derived chemokine (MDC). Of the chemokines tested, SDF-1 and MDC were
      the only 2 that activated platelets. Both are weak agonists, but they enhanced
      response to low-dose adenosine 5'-diphosphate (ADP), epinephrine, or serotonin.
      When SDF-1 and MDC were added together, full and brisk platelet aggregation
      occurred. Platelet activation by these 2 chemokines appears to involve distinct
      pathways: SDF-1 inhibited an increase in cyclic adenosine monophosphate (cAMP)
      following prostaglandin (PG) I(2), while MDC had no effect. In contrast, MDC, but
      not SDF-1, lead to Ca(++) mobilization by platelets. Further, second-wave
      aggregation induced by MDC in platelet-rich plasma was inhibited by aspirin, ADP
      scavenger creatine phosphate/creative phosphokinase (CP/CPK), and ARL-66096, an
      antagonist of the ADP P2T(AC) receptor involved in adenylyl cyclase inhibition.
      But the aggregation was not affected by A3P5PS, an inhibitor of the ADP P2Y
      receptor. SDF-1-induced aggregation was inhibited by aspirin, but it was only
      slightly affected by CP/CPK, ARL-66096, or A3P5PS. Finally, the presence of
      chemokines in platelets was determined. Reverse transcriptase-polymerase chain
      reaction studies with platelet RNA did not detect the presence of SDF-1 or MDC.
      In summary, SDF-1 and MDC are platelet agonists that activate distinct
      intracellular pathways. Their importance in the development of thrombosis at
      sites of inflammation needs to be further evaluated.

PMID- 10891431
TI  - Consensus strategy to quantitate malignant cells in myeloma patients is validated
      in a multicenter study. Belgium-Dutch Hematology-Oncology Group.
AB  - Recently the Belgium-Dutch Hematology-Oncology group initiated a multicenter
      study to evaluate whether myeloma patients treated with intensive chemotherapy
      benefit from additional peripheral stem cell transplantation. To determine
      treatment response accurately, we decided to quantitate malignant cells. To test
      a consensus quantitation strategy, 5 centers independently determined the
      immunoglobulin heavy chain sequences of patient tumor cells and developed allele
      specific oligonucleotides (ASO) and ASO-polymerase chain reaction (PCR). We
      compared the reproducibility of real-time quantitation with quantitation using
      limiting dilutions. We distributed DNA samples with a 4-log range of tumor cell
      concentrations and found average quantitation values deviating 74% and 42% from
      the input values with real-time PCR (1 center) and limiting dilutions (4
      centers), respectively. Within single centers we found an average variation
      coefficient of 0.74, with limiting dilutions not significantly different from the
      average 0.82 center-to-center variation coefficient. Within a single center, real
      time quantitation proved more reproducible (average variation coefficient, 0.36).
      Quantification was confirmed in 3 patients during treatment in the protocol. This
      report shows that real-time PCR or limiting dilution assays can be used for
      quantitation in a single multicenter trial. We present a consensus strategy that
      allows an accurate comparison of quantitation data generated in independent
      centers.

PMID- 10891432
TI  - Fludarabine and cyclophosphamide with filgrastim support in patients with
      previously untreated indolent lymphoid malignancies.
AB  - To evaluate the response rate and potential toxicities, a phase II trial was
      conducted of fludarabine and cyclophosphamide with filgrastim support in patients
      with previously untreated low-grade and select intermediate-grade lymphoid
      malignancies. Symptomatic patients with preserved end organ function received
      cyclophosphamide 600 mg/m(2) intravenous (iv) day 1 and fludarabine 20 mg/m(2) iv
      days1 through 5, followed by filgrastim 5 microg/kg subcutaneous starting
      approximately day 8. Treatment was repeated every 28 days until maximum response
      or a maximum of 6 cycles. Sixty patients, median age 53.5 years, were enrolled.
      Thirty-seven patients with non-Hodgkin lymphoma (NHL) were stage IV and 6 were
      stage III. Eleven of 17 patients with chronic lymphocytic leukemia (CLL) were Rai
      intermediate risk and 6 were high risk. The overall complete response (CR) rate
      was 51% and the partial response (PR) rate was 41%. Of patients with CLL, 47%
      achieved a CR and the remaining 53% achieved a PR. Of patients with follicular
      lymphoma, 60% achieved CR and 32% achieved a PR. Although the toxicity of this
      regimen was mainly hematologic, significant nonhematologic toxicities, including
      infections, were seen. Twenty-four patients subsequently received an autologous
      or allogeneic stem cell transplant. Engraftment was rapid, and there were no
      noticeable procedure toxicities in the immediate posttransplant period
      attributable to the fludarabine and cyclophosphamide regimen. Fludarabine,
      cyclophosphamide, and filgrastim make up a highly active and well-tolerated
      regimen in CLL and NHL.

PMID- 10891433
TI  - Severity of iron overload in patients with sickle cell disease receiving chronic
      red blood cell transfusion therapy.
AB  - Chronic transfusion therapy is being used more frequently to prevent and treat
      the complications of sickle cell disease. Previous studies have shown that the
      iron overload that results from such therapy in other patient populations is
      associated with significant morbidity and mortality. In this study we examined
      the extent of iron overload as well as the presence of liver injury and the
      predictive value of ferritin in estimating iron overload in children with sickle
      cell disease who receive chronic red blood cell transfusions. A poor correlation
      was observed between serum ferritin and the quantitative iron on liver biopsy
      (mean 13.68 +/- 6.64 mg/g dry weight; R = 0.350, P =.142). Quantitative iron was
      highly correlated with the months of transfusion (R = 0.795, P <.001), but serum
      ferritin at biopsy did not correlate with months of transfusion (R = 0.308, P
      =.200). Sixteen patients had abnormal biopsies showing mild to moderate changes
      on evaluation of inflammation or fibrosis. Liver iron was correlated with
      fibrosis score (R = 0.50, P =.042). No complications were associated with the
      liver biopsy. Our data suggest that, in patients with sickle cell disease,
      ferritin is a poor marker for accurately assessing iron overload and should not
      be used to direct long-term chelation therapy. Despite high levels of liver iron,
      the associated liver injury was not severe.

PMID- 10891434
TI  - A randomized, double-blind trial of filgrastim (granulocyte colony-stimulating
      factor) versus placebo following allogeneic blood stem cell transplantation.
AB  - Blood stem cell transplantation (BSCT) results in rapid hematopoietic recovery in
      both the allogeneic and autologous transplant settings. Because of the large
      numbers of progenitor cells in mobilized blood, the administration of growth
      factors after transplantation may not provide further acceleration of
      hematopoietic recovery. A randomized, double-blind, placebo-controlled study was
      performed to determine the effects of filgrastim (granulocyte colony-stimulating
      factor; G-CSF) administration on hematopoietic recovery after allogeneic BSCT.
      Fifty-four patients with hematologic malignancies undergoing a related, HLA
      matched allogeneic BSCT were randomly assigned to receive daily filgrastim at 10
      microg/kg or placebo starting on the day of transplantation. A minimum of 3 x
      10(6) CD34(+) cells/kg in the allograft was required for transplantation. All
      patients received a standard preparative regimen and a standard regimen for the
      prevention of graft-versus-host disease (GVHD). The median time to achieve an
      absolute neutrophil count greater than 0.5 x 10(9)/L was 11 days (range, 9-20
      days) for patients who received filgrastim compared with 15 days (range, 10-22
      days) for patients who received placebo (P =.0082). The median time to achieve a
      platelet count greater than 20 x 10(9)/L was 13 days (range, 8-35 days) for
      patients who received filgrastim compared with 15.5 days (range, 8-42 days) for
      patients who received placebo (P =.79). There were no significant differences for
      red blood cell transfusion independence, the incidence of acute GVHD, or 100-day
      mortality between the groups. The administration of filgrastim appears to be a
      safe and effective supportive-care measure following allogeneic BSCT.

PMID- 10891435
TI  - Estimating leukemia-free survival after allografting for chronic myeloid
      leukemia: a new method that takes into account patients who relapse and are
      restored to complete remission.
AB  - A significant number of patients who relapse after allogeneic stem cell
      transplantation (SCT) for chronic myeloid leukemia (CML) will achieve sustained
      remissions after treatment with interferon-alpha, second transplants, or donor
      lymphocyte infusions (DLI) from the original stem cell donor. Because leukemia
      free survival (LFS) is at present defined as survival without evidence of relapse
      at any time posttransplant, patients who relapse but are then restored to
      complete remission are treated as failures when estimating LFS. We have
      established a new category of LFS, termed current LFS (CLFS), which we define as
      survival without evidence of leukemia at the time of most recent assessment. To
      gauge the contribution of treatment for relapse to the efficacy of allogeneic SCT
      in the management of CML in chronic phase, we compared conventional LFS and CLFS
      in 189 consecutive patients who underwent SCT over a 7-year period with a minimum
      follow-up of 3 years. Patients with sibling donors (n = 111) received
      cyclosporine and methotrexate as prophylaxis for graft versus host disease;
      patients with unrelated donors (n = 78) also received Campath-1G or 1H as
      intravenous T-cell depletion. The 5-year LFS defined conventionally was 36% (CI:
      29% to 43%) versus a 5-year CLFS of 49% (CI: 36% to 62%). This new method of
      defining LFS confirms the view that appropriate "salvage" therapy, principally
      DLI, makes a major contribution to the capacity of allogeneic SCT to produce long
      term LFS in patients who receive SCT for CML and emphasizes the importance of
      redefining LFS to take account of successful treatment of relapse.

PMID- 10891436
TI  - Dendritic cells modified to express CD40 ligand elicit therapeutic immunity
      against preexisting murine tumors.
AB  - CD40 ligand (CD40L) is essential for the initiation of antigen-specific T-cell
      responses. This study is based on the hypothesis that dendritic cells (DCs)
      genetically modified ex vivo to express CD40L will enhance in vivo presentation
      of tumor antigen to the cellular immune system with consequent induction of
      antitumor immunity to suppress tumor growth. To examine this concept,
      subcutaneous murine tumors were injected with bone marrow-derived DCs that had
      been modified in vitro with an adenovirus (Ad) vector expressing murine CD40L
      (AdmCD40L). In B16 (H-2(b), melanoma) and CT26 (H-2(d), colon cancer) murine
      models, intratumoral injection of 2 x 10(6) AdmCD40L-modified DCs (CD40L-DCs) to
      established (day 8) subcutaneous tumors resulted in sustained tumor regression
      and survival advantage. This antitumor effect was sustained when the number of
      CD40L-DCs were reduced 10-fold to 2 x 10(5). Analysis of spleens from CD40L-DC
      treated animals demonstrated that CD40L-DCs injected into the subcutaneous CT26
      flank tumors migrated to the spleen, resulting in activation of immune-relevant
      processes. Consistent with this concept, intratumoral administration of CD40L-DCs
      elicited tumor-specific cytotoxic T-lymphocyte responses, and the transfer of
      spleen cells from CD40L-DC-treated mice efficiently protected naive mice against
      a subsequent tumor challenge. In a distant 2-tumor model of metastatic disease,
      an untreated B16 tumor in the right flank regressed in parallel with a left B16
      tumor treated with direct injection of CD40L-DCs. These results support the
      concept that genetic modification of DCs with a recombinant CD40L adenovirus
      vector may be a useful strategy for directly activating DCs for cancer
      immunotherapy.

PMID- 10891438
TI  - Rapid selection of antigen-specific T lymphocytes by retroviral transduction.
AB  - Infusions of donor peripheral blood T cells can induce durable remissions of
      Epstein-Barr virus (EBV) lymphomas complicating marrow grafts, but they contain
      alloreactive T cells capable of inducing graft-versus-host disease. EBV-specific
      T-cell lines or clones avoid this problem but require 30 to 40 days of culture to
      establish. To accelerate the generation of EBV-specific T cells, we tested
      whether retroviral vectors, which only integrate in dividing cells, could be used
      to transduce and select antigen-reactive T cells early after sensitization to
      autologous EBV-transformed B cells. T cells were transduced with a dicistronic
      retroviral vector, NIT, which encodes low-affinity nerve growth factor receptor
      as an immunoselectable marker and herpes simplex virus thymidine kinase as a
      suicide gene, at different time points after sensitization. EBV-specific
      cytotoxic T lymphocyte precursor (CTLp) frequencies in purified NIT(+) T-cell
      fractions transduced on day 8 of culture were comparable to those of EBV-specific
      T-cell lines cultured for 30 days or more. Alloreactive CTLp frequencies were
      markedly reduced in the NIT(+) fraction relative to the untransduced T-cell
      population. NIT(+) fractions transduced on day 8 possessed more CD4(+) T cells
      than the cell lines at day 30 and exhibited the same selective pattern of
      reactivity against immunodominant antigens presented by specific HLA alleles. In
      contrast, T cells transduced with NIT 5 days after stimulation with mitogen and
      interleukin-2 were relatively depleted of T cells specific for autologous EBV
      transformed cells. Thus, retroviral vectors may be used for rapid selection of
      viral antigen-reactive T cells depleted of alloreactive T cells.

PMID- 10891437
TI  - Adenoviral vector-mediated gene transfer to primitive human hematopoietic
      progenitor cells: assessment of transduction and toxicity in long-term culture.
AB  - Adenoviral gene transfer to primitive hematopoietic progenitor cells (HPCs) would
      be useful in gene therapy applications where transient, high-level transgene
      expression is required. In the present investigations, we have used an adenoviral
      vector expressing the green fluorescent protein (AdGFP) to quantify transduction
      of primitive HPCs and assess adenoviral-associated toxicity in long-term culture.
      Here we show that a cytokine cocktail protects mass populations of CD34(+) cells
      and primary colony forming unit-cultures (CFU-Cs) from toxicity, enabling
      transduction of up to 79% of CD34(+) cells. Transduction of CFU-Cs and more
      primitive HPCs was quantified following fluorescence activated cell sorting for
      green flourescence protein expression. Our results demonstrate transduction of
      45% of primary CFU-Cs, 33% of week-5 cobblestone area forming cells (CAFCs), and
      18% of week-5 CFU-Cs. However, AdGFP infection inhibited proliferation of more
      primitive cells. Although there was no apparent quantitative change in week-5
      CAFCs, the clonogenic capacity of week-5 AdGFP-infected cells was reduced by 40%
      (P <.01) when compared with mock-infected cells. Adenoviral toxicity specifically
      affected the transduced subset of primitive HPCs. Transduction of primitive cells
      is therefore probably underestimated by week-5 CFU-Cs and more accurately
      indicated by week-5 CAFCs. These studies provide the first functional and
      quantitative evidence of adenoviral transduction of primitive HPCs. However,
      further investigations will be necessary to overcome adenoviral toxicity toward
      primitive HPCs before adenoviral vectors can be considered a safe option for gene
      therapy.

PMID- 10891439
TI  - Autosomal dominant thrombocytopenia: incomplete megakaryocyte differentiation and
      linkage to human chromosome 10.
AB  - We studied a large kindred with nonsyndromic autosomal dominant thrombocytopenia
      to define the phenotype and used genomic linkage analysis to determine the locus
      of the abnormal gene. Affected family members are characterized by lifelong
      moderate thrombocytopenia (mean = 42.7 x 10(9)/L) with moderate propensity toward
      easy bruising and minor bleeding. Megakaryocytes are present in bone marrow with
      reduced frequency, and there are no apparent abnormalities of myeloid or
      erythroid cells. This type of inherited thrombocytopenia has no evident
      association with hematopoietic malignancy or progression to aplastic anemia. In
      the past, members of this family have failed therapeutic trials of
      immunosuppression and splenectomy. In our investigation, we found that affected
      individuals had normal platelet size compared with unaffected family members and
      modestly increased thrombopoietin levels. Hematopoietic colony assays from bone
      marrow and peripheral blood demonstrated that megakaryocyte precursors (CFU-Mk)
      were dramatically increased in both number and size in affected individuals. Bone
      marrow cells grown in liquid culture with thrombopoietin failed to develop
      polyploid cells greater than 8N. Also, electron microscopy demonstrated that
      megakaryocytes from an affected individual had markedly delayed nuclear and
      cytoplasmic differentiation. Genome-wide linkage analysis established a single
      locus for the disease gene on the short arm of chromosome 10 with a maximum 2
      point lod score of 5.68 (at theta = 0). By recruiting additional family members,
      the genomic region was narrowed to 17 centimorgans. We conclude that a gene in
      this locus plays an important role in megakaryocyte endomitosis and terminal
      maturation.

PMID- 10891440
TI  - Infection of CD34(+) hematopoietic progenitor cells by human herpesvirus 7 (HHV
      7).
AB  - To investigate the tropism of the T-lymphotropic human herpesvirus 7 (HHV-7) for
      hematopoietic progenitors, cord blood CD34(+) cells were inoculated in vitro with
      HHV-7 and then induced to differentiate along the granulocytic and erythroid
      lineages by the addition of appropriate cytokine cocktails. In semisolid assays,
      HHV-7 modestly affected the growth of committed (granulocytic/macrophagic and
      erythroid) progenitors, whereas it significantly decreased the number of
      pluripotent (granulocytic/erythroid/ monocytic/megakaryocytic) progenitors. Such
      inhibitory effect was completely abrogated by incubating HHV-7 inoculum with anti
      HHV-7 neutralizing serum. In liquid cultures, HHV-7 hastened maturation along the
      myeloid but not the erythroid lineage, as demonstrated by the up-regulation of
      CD33 early myeloid antigen at day 7 of culture, and of CD15 and CD14 antigens at
      day 15. Moreover, HHV-7 messenger RNA was detected by reverse transcriptase
      polymerase chain reaction (RT-PCR) in cells maturating along both the myeloid and
      the erythroid lineages. To evaluate the relevance of these in vitro findings, the
      presence of HHV-7 was investigated in bone marrow (BM) unfractionated mononuclear
      cells (MCs) as well as in purified CD34(+) and CD34(-) cell subsets, obtained
      from 14 normal adult donors. HHV-7 DNA was detected by DNA-PCR in 4 of 7 BMMC
      samples, and it was found to be associated with both the CD34(-) (2 of 7) and the
      CD34(+ )(1 of 7) fractions. These data indicate that HHV-7 infects BM cells in
      vivo and shows the ability to affect the survival/differentiation of CD34(+)
      hematopoietic progenitors in vitro by inhibiting more ancestral progenitors and
      perturbing the maturation of myeloid cells.

PMID- 10891441
TI  - The shc adaptor protein forms interdependent phosphotyrosine-mediated protein
      complexes in mast cells stimulated with interleukin 3.
AB  - The Shc adaptor protein possesses 2 distinct phosphotyrosine (pTyr) recognition
      modules-the pTyr binding (PTB) domain and the Src homology 2 (SH2) domain-and
      multiple potential sites for tyrosine (Tyr) phosphorylation (Tyr residues 239,
      240, and 317). On stimulation of hematopoietic cells with interleukin 3 (IL-3),
      Shc becomes phosphorylated and may therefore contribute to IL-3 signaling. We
      investigated the interactions mediated by the Shc modular domains and pTyr sites
      in IL-3-dependent IC2 premast cells. The Shc PTB domain, rather than the SH2
      domain, associated both in vitro and in vivo with the Tyr-phosphorylated beta
      subunit of the IL-3 receptor and with the SH2-containing 5' inositol phosphatase
      (SHIP), and it recognized specific NXXpY phosphopeptides from these binding
      partners. In IL-3-stimulated mast cells, Shc phosphorylation occurred primarily
      on Tyr239 and 317 and was dependent on a functional PTB domain. Phosphorylated
      Tyr317, and to a lesser extent, Tyr239, bound the Grb2 adaptor and SHIP.
      Furthermore, a pTyr317 Shc phosphopeptide selectively recognized Grb2, Sos1,
      SHIP, and the p85 subunit of phosphatidylinositol 3' kinase from mast cells, as
      characterized by mass spectrometry. These results indicate that Shc undergoes an
      interdependent series of pTyr-mediated interactions in IL-3-stimulated mast
      cells, resulting in the recruitment of proteins that regulate the Ras pathway and
      phospholipid metabolism.

PMID- 10891442
TI  - Sphingosine-1-phosphate and lysophosphatidic acid trigger invasion of primitive
      hematopoietic cells into stromal cell layers.
AB  - A new primitive hematopoietic cell line (THS119), exhibiting Lin(-)/Sca-1(+)/c
      Kit(+) a surface phenotype, grew and survived underneath stromal cells (TBR59).
      The ability of the THS119 cells to invade these stromal cell layers was dependent
      on the inclusion of serum in the culture medium. This was apparently due to a
      requirement for lipids contained in serum. Their invasion of the stromal cell
      layers in serum-free cultures could be triggered by addition of sphingosine-1
      phosphate (S1P) or lysophosphatidic acid (LPA) and was dependent on both Rho- and
      Ras-signaling pathways. Between the 2 possible receptors of S1P and LPA, edg-1
      and edg-2, expression of edg-2 only was found to be correlated with immaturity
      and/or invasive activity of the primitive hematopoietic cells. These results
      suggest the importance of specific lipids and their specific receptors on the
      invasive activity of primitive hematopoietic cells in the hematopoietic
      microenvironment.

PMID- 10891443
TI  - The elusive factor Xa receptor: failure to detect transcripts that correspond to
      the published sequence of EPR-1.
AB  - The coagulation protease factor Xa induces cellular responses implicated in
      cardiovascular and inflammatory disease. Effector-cell protease receptor 1 (EPR
      1) is a functionally characterized receptor of factor Xa, and the EPR-1
      complementary DNA (cDNA) was published. Remarkably, the cDNA encoding an
      inhibitor of apoptosis, survivin, is reportedly identical to that of EPR-1 except
      for a few nucleotide differences and its orientation opposite to EPR-1. To
      isolate the EPR-1 cDNA and gene, we surveyed gene databases for expressed
      sequence tags (ESTs) that could be derived from EPR-1. All ESTs with strong
      homology to EPR-1/survivin were derived from survivin and could not encode EPR-1.
      By polymerase chain reaction and Southern blot hybridization, EPR-1 was not
      detectable in the human or murine genome, but survivin was. Our data suggest that
      EPR-1 is either highly cell-specific or the published EPR-1 cDNA includes
      sequences from clones derived from survivin messenger RNA. The means by which
      factor Xa mediates its cellular effects requires further evaluation.

PMID- 10891444
TI  - Mutations in the fibrinogen aalpha gene account for the majority of cases of
      congenital afibrinogenemia.
AB  - Congenital afibrinogenemia is a rare, autosomal, recessive disorder characterized
      by the complete absence of detectable fibrinogen. We previously identified the
      first causative mutations in a nonconsanguineous Swiss family; the 4 affected
      persons have homozygous deletions of approximately 11 kb of the fibrinogen alpha
      (FGA) gene. Haplotype data implied that these deletions occurred on distinct
      ancestral chromosomes, suggesting that this region may be susceptible to deletion
      by a common mechanism. We subsequently showed that all the deletions were
      identical to the base pair and probably resulted from a nonhomologous
      recombination mediated by 7-bp direct repeats. In this study, we have collected
      data on 13 additional unrelated patients to identify the causative mutations and
      to determine the prevalence of the 11-kb deletion. A common recurrent mutation,
      at the donor splice site of FGA intron 4 (IVS4 + 1 G > T), accounted for 14 of
      the 26 (54%) alleles. One patient was heterozygous for the previously identified
      deletion. Three more frameshift mutations, 2 nonsense mutations, and a second
      splice site mutation were also identified. Consequently, 86% of afibrinogenemia
      alleles analyzed to date have truncating mutations of FGA, though mutations in
      all 3 fibrinogen genes, FGG, FGA, and FGB, might be predicted to cause congenital
      afibrinogenemia.

PMID- 10891445
TI  - Vascular release of plasminogen activator inhibitor-1 impairs fibrinolysis during
      acute arterial thrombosis in mice.
AB  - The role of plasminogen activator inhibitor-1 (PAI-1) in the plasma, blood
      platelets, and vessel wall during acute arterial thrombus formation was
      investigated in gene-deficient mice. Photochemically induced thrombosis in the
      carotid artery was analyzed via transillumination. In comparison to thrombosis in
      C57BL/6J wild-type (wt) mice (113 +/- 19 x 10(6) arbitrary light units [AU] n =
      15, mean +/- SEM), thrombosis in PAI-1(-/-) mice (40 +/- 10 x 10(6) AU, n = 13)
      was inhibited (P <.01), indicating that PAI-1 controls fibrinolysis during
      thrombus formation. Systemic administration of murine PAI-1 into PAI-1(-/-) mice
      led to a full recovery of thrombotic response. Occurrence of fibrinolytic
      activity was confirmed in alpha(2)-antiplasmin (alpha(2)-AP)-deficient mice. The
      sizes of thrombi developing in wt mice, in alpha(2)-AP(+/-) and alpha(2)-AP(-/-)
      mice were 102 +/- 35, 65 +/- 8.1, and 13 +/- 6.1 x 10(6) AU, respectively (n = 6
      each) (P <.05), compatible with functional plasmin inhibition by alpha(2)-AP. In
      contrast, thrombi in wt mice, t-PA(-/-) and u-PA(-/-) mice were comparable,
      substantiating efficient inhibition of fibrinolysis by the combined PAI
      1/alpha(2)-AP action. Platelet depletion and reconstitution confirmed a normal
      thrombotic response in wt mice, reconstituted with PAI-1(-/-) platelets, but weak
      thrombosis in PAI-1(-/-) mice reconstituted with wt platelets. Accordingly,
      murine (wt) PAI-1 levels in platelet lysates and releasates were 0.43 +/- 0.09
      ng/10(9) platelets and plasma concentrations equaled 0.73 +/- 0.13 ng/mL. After
      photochemical injury, plasma PAI-1 rose to 2.9 +/- 0.7 ng/mL (n = 9, P <.01). The
      plasma rise was prevented by ligating the carotid artery. Hence, during acute
      thrombosis, fibrinolysis is efficiently prevented by plasma alpha(2)-AP, but also
      by vascular PAI-1, locally released into the circulation after endothelial
      injury.

PMID- 10891446
TI  - A Leu262Pro mutation in the integrin beta(3) subunit results in an alpha(IIb)
      beta(3) complex that binds fibrin but not fibrinogen.
AB  - Platelet retraction of a fibrin clot is mediated by the platelet fibrinogen
      receptor, alpha(IIb)beta(3). In certain forms of the inherited platelet disorder,
      Glanzmann thrombasthenia (GT), mutant alpha(IIb)beta(3) may interact normally
      with fibrin yet fail to support fibrinogen-dependent aggregation. We describe a
      patient (LD) with such a form of GT. Platelets from LD supported normal clot
      retraction but failed to bind fibrinogen. Platelet analysis using flow cytometry
      and immunoblotting showed reduced but clearly detectable alpha(IIb)beta(3),
      findings consistent with type II GT. Genotyping of LD revealed 2 novel beta(3)
      mutations: a deletion of nucleotides 867 to 868, resulting in a premature stop
      codon at amino acid residue 267, and a T883C missense mutation, resulting in a
      leucine (Leu) 262-to-proline (Pro) substitution. Leu262 is highly conserved among
      beta integrin subunits and lies within an intrachain loop implicated in subunit
      association. Leu262Probeta(3) cotransfected with wild-type alpha(IIb) into COS-7
      cells showed delayed intracellular maturation and reduced surface expression of
      easily dissociable complexes. In human embryonic kidney 293 cells,
      Leu262Probeta(3) formed a complex with endogenous a(v) and retracted fibrin clots
      similarly to wild-type beta(3). The same cells, however, were unable to bind
      immobilized fibrinogen. The molecular requirements for alpha(IIb)beta(3) to
      interact with fibrin compared with fibrinogen, therefore, appear to differ. The
      region surrounding beta(3) Leu262 may maintain beta(3) in a fibrinogen-binding,
      competent form, but it appears not to be required for receptor interactions with
      fibrin.

PMID- 10891447
TI  - Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and
      tissue factor.
AB  - We describe thrombogenic tissue factor (TF) on leukocyte-derived microparticles
      and their incorporation into spontaneous human thrombi. Polymorphonuclear
      leukocytes and monocytes transfer TF(+) particles to platelets, thereby making
      them capable of triggering and propagating thrombosis. This phenomenon calls into
      question the original dogma that vessel wall injury and exposure of TF within the
      vasculature to blood is sufficient for the occurrence of arterial thrombosis. The
      transfer of TF(+) leukocyte-derived particles is dependent on the interaction of
      CD15 and TF with platelets. Both the inhibition of TF transfer to platelets by
      antagonizing the interaction CD15 with P-selectin and the direct interaction of
      TF itself suggest a novel therapeutic approach to prevent thrombosis.

PMID- 10891448
TI  - Bactericidal/permeability-increasing protein (BPI) inhibits angiogenesis via
      induction of apoptosis in vascular endothelial cells.
AB  - Bactericidal/permeability-increasing protein (BPI) has been known for some time
      to function in killing bacteria and in neutralizing the effects of bacterial
      endotoxin lipopolysaccharide. In the present study, BPI is found to be a novel
      endogenous inhibitor of angiogenesis. Within the sub-muM range, BPI shows a
      concentration-dependent inhibition of endothelial cell (EC) proliferation that is
      mediated by cell detachment and subsequent induction of apoptosis. As measured by
      flow cytometric analysis of the percentage of subdiploid cells, apoptosis
      induction was half-maximal at about 250 nmol/L BPI. Apoptosis was confirmed by
      quantification of cells with nuclear fragmentation. Apoptosis was found to be EC
      specific. In an in vitro collagen gel-based angiogenesis assay, BPI at 1.8
      micromol/L inhibited tube formation by 81% after only 24 hours. Evidence for in
      vivo inhibition of angiogenesis was obtained, using the chorioallantoic membrane
      assay in which BPI was seen to be significantly effective at concentrations as
      low as 180 nmol/L. This newly discovered function of BPI might provide a possible
      therapeutic modality for the treatment of various pathologic disorders that
      depend on angiogenesis.

PMID- 10891449
TI  - Heparin-induced thrombocytopenia: new evidence for the dynamic binding of
      purified anti-PF4-heparin antibodies to platelets and the resultant platelet
      activation.
AB  - Immune heparin-induced thrombocytopenia (HIT) is associated with antibodies
      directed against a complex of platelet factor 4 (PF4) and heparin. We were able
      to affinity purify anti-PF4-heparin IgG (HIT IgG) from the plasma of 2 patients
      with HIT. Under conditions that were more physiological and sensitive than those
      in previous studies, we observed that this HIT IgG caused platelet aggregation on
      the addition of heparin. Platelets activated with HIT IgG increased their release
      and surface expression of PF4. We quantitated, for the first time, the binding of
      affinity-purified HIT iodine 125-IgG to platelets as they activated in a plasma
      milieu. Binding of the HIT IgG was dependent on heparin and required some degree
      of platelet activation. Blocking the platelet FcgammaRII with the monoclonal
      antibody IV.3 did not prevent HIT IgG binding to activated platelets. We
      concluded that anti-PF4-heparin IgG is the component in these HIT plasmas that
      induces platelet aggregation. The Fab region of HIT IgG binds to PF4-heparin on
      the surface of activated platelets. We propose that only then does the Fc portion
      of the bound IgG further activate the same or adjacent platelets through the Fc
      receptor. Our data support a dynamic model of platelet activation in which
      released PF4 enhances further antibody binding and more release.

PMID- 10891450
TI  - Morphological analysis of microparticle generation in heparin-induced
      thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) with thrombosis is a serious complication
      of heparin use. HIT sera can generate platelet-derived microparticles, which are
      produced in a heparin-dependent manner and are hypothesized to be important
      initial pathological participants because they promote vascular occlusion. To
      date, microparticles have been studied using flow cytometric techniques. However,
      it is uncertain whether the small-sized material seen in flow cytometric studies
      represents true platelet microparticles shed from activated platelets or whether
      they are platelets that have contracted after releasing their internal
      components. This report describes a morphological investigation of platelet
      derived microparticles in HIT using, among other techniques, confocal, scanning
      electron, and transmission electron microscopy. Following incubation with HIT
      sera, the existence of small membrane-bound vesicles in the milieu of activated
      platelets was demonstrated. A population of microparticles, expressing platelet
      specific glycoproteins, was separated from platelets by centrifugation over a
      sucrose layer. These microparticles had identical flow cytometric profiles, size
      heterogeneity, and GPIb(alpha) and GPIIb/IIIa staining intensity as the
      microparticle population in unfractionated samples. When microparticles were
      generated in situ and fixed onto grids, they were demonstrated to be distinct
      membrane-bound vesicles that originated near the platelet body and terminal ends
      of pseudopods on activated platelets. These microparticles appeared to be
      generated by localized swelling, budding, and release. Collectively, these
      morphological studies document the existence of true microparticles in platelets
      activated by HIT sera. The microparticles may play an important role in the
      pathogenesis of HIT.

PMID- 10891451
TI  - CD4 T lymphocytes are primed to express Fas ligand by CD4 cross-linking and to
      contribute to CD8 T-cell apoptosis via Fas/FasL death signaling pathway.
AB  - CD4 molecules serve as coreceptors for the T-cell receptor (TCR)/CD3 complex that
      are engaged coordinately with TCR and facilitate antigen-specific T-cell
      activation leading to interleukin 2 (IL-2) production and proliferation. However,
      cross-ligation of CD4 molecules prior to TCR stimulation has been shown to prime
      CD4 T cells to undergo apoptosis. Although in vivo and in vitro experiments have
      implicated the involvement of Fas/FasL interaction in this CD4 cross-linking
      (CD4XL)-induced apoptosis, detailed mechanisms to account for cell death
      induction have not been elucidated. In the present study, we demonstrate that
      CD4XL in purified T cells not only led to Fas up-regulation but also primed CD4 T
      cells to express FasL upon CD3 stimulation and rendered the T cells susceptible
      to Fas-mediated apoptosis. Notably, in addition to CD4(+) T cells, CD4XL-induced
      sensitization for apoptosis was observed in CD8(+) T cells as well and was
      associated with Bcl-x down-modulation. Both CD4 and CD8 T-cell subsets underwent
      apoptosis following cell-cell contact with FasL(+) CD4 T cells. CD28
      costimulation abrogated CD4XL/CD3-induced apoptosis with restoration of IL-2
      production and prevented Bcl-x down-modulation. As CD4 molecules are the primary
      receptors for human immunodeficiency virus 1 (HIV-1), we conclude that HIV-1
      envelope mediated CD4XL can lead to the generation of FasL-expressing CD4(+) T
      cells that can lead to apoptosis of CD4 as well as CD8 T cells. These findings
      implicate a novel mechanism for CD8 T-cell depletion in HIV disease.

PMID- 10891452
TI  - N-terminal truncated human RAG1 proteins can direct T-cell receptor but not
      immunoglobulin gene rearrangements.
AB  - The proteins encoded by RAG1 and RAG2 can initiate gene recombination by site
      specific cleavage of DNA in immunoglobulin and T-cell receptor (TCR) loci. We
      identified a new homozygous RAG1 gene mutation (631delT) that leads to a
      premature stop codon in the 5' part of the RAG1 gene. The patient carrying this
      631delT RAG1 gene mutation died at the age of 5 weeks from an Omenn syndrome-like
      T(+)/B(- )severe combined immunodeficiency disease. The high number of blood T
      lymphocytes (55 x 10(6)/mL) showed an almost polyclonal TCR gene rearrangement
      repertoire not of maternal origin. In contrast, B-lymphocytes and immunoglobulin
      gene rearrangements were hardly detectable. We showed that the 631delT RAG1 gene
      can give rise to an N-terminal truncated RAG1 protein, using an internal AUG
      codon as the translation start site. Consistent with the V(D)J recombination in T
      cells, this N-terminal truncated RAG1 protein was active in a plasmid V(D)J
      recombination assay. Apparently, the N-terminal truncated RAG1 protein can
      recombine TCR genes but not immunoglobulin genes. We conclude that the N-terminus
      of the RAG1 protein is specifically involved in immunoglobulin gene
      rearrangements.

PMID- 10891453
TI  - Interferon-alpha and -beta inhibit the in vitro differentiation of
      immunocompetent human dendritic cells from CD14(+) precursors.
AB  - Dendritic cell (DC) precursors and immature DC reside in epithelium where they
      encounter pathogens and cytokines, which stimulate their differentiation. We
      hypothesized that type-I interferons (IFN-alpha and -beta), cytokines that are
      produced early in the innate immune response against viruses and some bacteria,
      may influence DC differentiation and function. To examine this possibility, we
      used an in vitro model of DC differentiation in which initial culture of human
      CD14(+) monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF)
      and interleukin (IL)-4 generates immature DC, and subsequent culture with tumor
      necrosis factor (TNF)-alpha drives the final development into mature DC. We found
      in this model that IFN-alpha/beta, added from the initiation of the culture on,
      significantly reduced the survival and altered the morphology and differentiation
      of DC. TNF-alpha-dependent maturation of IFN-beta-treated immature DC led to
      cells with reduced expression of CD1a, CD40, CD54, and CD80 when compared with
      mature DC controls. IFN-alpha/beta-treated DC further had a reduced capacity to
      induce naive Th-cell proliferation through allostimulation or anti-CD3 monoclonal
      antibody stimulation. In addition, IFN-alpha/beta-treated DC secreted less IL-12
      upon stimulation with Staphylococcus aureus Cowan strain or with CD4(+) T cells,
      and this decrease correlated directly with their inability to support CD4(+) T
      cell secretion of IFN-gamma, even though T-cell lymphotoxin production was
      unaffected. These findings indicate that type-I IFNs can influence the generation
      of acquired immune responses by modifying T-helper cell differentiation through
      the regulation of DC differentiation and function.

PMID- 10891454
TI  - Impaired antigen presentation by human monocytes during endotoxin tolerance.
AB  - Endotoxin tolerance (ET) has been described as a temporary alteration in the
      lipopolysaccharide (LPS) response of monocytic cells after an initial LPS
      exposure with respect to the production of soluble immunomodulators. Apart from
      the LPS response, monocytic cells play an important role in initiation of the
      specific immune response as antigen-presenting cells. This study investigated the
      capacity of human blood monocytes to induce T-cell stimulation in ET. First, the
      expression of monocyte surface molecules, important for T-cell interaction, was
      analyzed by flow cytometry. In vitro priming of peripheral blood mononuclear
      cells with LPS clearly down-regulates major histocompatibility complex class II
      molecules and the costimulatory molecule CD86. Both changes were dependent on the
      endogenous interleukin (IL)-10 and less so on the transforming growth factor
      beta. In contrast, other accessory molecules on monocytes were only marginally
      down-regulated (CD58), were not significantly changed during ET (CD40), or even
      remained up-regulated after initial LPS priming (CD54, CD80). Second, an impact
      of these phenotypic alterations on the accessory function of monocytes was
      observed. This was manifested as diminished T-cell proliferation and interferon
      (IFN)-gamma release in response to the presence of different recall antigens.
      Neutralizing IL-10 during LPS priming prevented the diminished T-cell IFN-gamma
      production but had little effect on T-cell proliferation. These data confirm that
      ET is an appropriate model of the monocyte functional state in immunoparalysis,
      which is frequently observed in patients after septic shock, trauma, or major
      surgery.

PMID- 10891455
TI  - CD9 expression enhances the susceptibility of myeloma cell lines to cell-mediated
      cytolysis.
AB  - Myeloma tumor cells, both freshly excised and cultured, are extremely resistant
      to cell-mediated cytolysis. As evidence suggests that B-cell susceptibility to
      lysis is dependent upon its state of differentiation and activation, we tested
      the ability of a variety of B-cell proliferation and differentiation agents,
      including pokeweed mitogen (PWM), to enhance the sensitivity of myeloma cells to
      cell-mediated lysis. PWM was found to significantly enhance the susceptibility of
      myeloma cell lines and freshly isolated myeloma cells to interleukin-2 (IL-2)
      activated cell-mediated cytolysis. This effect was seen with the use of both IL-2
      stimulated natural killer (NK) cells and T cells as effectors. The enhanced
      sensitivity of myeloma cells to cytolysis correlated with an increase in their
      cell surface expression of CD9, a pre-B cell marker and member of the
      transmembrane 4 superfamily. Incubation of PWM-stimulated myeloma cells with
      either monoclonal antibodies or antisense oligonucleotides directed against CD9
      abrogated the effect of PWM. In order to determine whether there was a direct
      relationship between the expression of CD9 and enhanced sensitivity to cytolysis,
      myeloma cell lines that lacked CD9 expression were transfected with the CD9 gene.
      The level of cell surface CD9 expression correlates with enhanced susceptibility
      to lysis. Therefore, CD9 appears to be an important component in enhancing the
      sensitivity of myeloma cells to lysis mediated by IL-2-activated T cells and NK
      cells.

PMID- 10891456
TI  - Integrin-associated protein/CD47 regulates motile activity in human B-cell lines
      through CDC42.
AB  - Cell migration requires a dynamic interaction between the cell, its substrate,
      and the cytoskeleton-associated motile apparatus. Integrin-associated protein
      (IAP)/CD47 is a 50-kd cell surface protein that is physically associated with
      beta3 integrins and that modulates the functions of beta3 integrins in various
      cells. However, in B-lymphocytes that express beta1 integrins but few beta3
      integrins, the roles of IAP/CD47 remain to be determined. Cross-linking of
      IAP/CD47 by the immobilized anti-IAP/CD47 monoclonal antibody (mAb) B6H12, but
      not 2D3, produced signals to promote polarization with lamellipodia, a
      characteristic morphology during leukocyte migration, in pre-B and mature B-cell
      lines (BALL, Nalm6, ONHL-1, Daudi), but not in myeloma cell lines (RPMI8226, OPM
      2). In the presence of the immobilized fibronectin (FN), soluble B6H12 could
      increase the rate of the polarization and activate migratory activity of BALL
      cells to FN in a transwell filter assay. Furthermore, the dominant-negative form
      of CDC42 completely blocked B6H12-induced morphologic and functional changes
      without inhibiting phorbol 12-myristate 13-acetate-induced spreading on FN in
      BALL cells, whereas the dominant-negative form of Rac1 inhibited all these
      changes. These findings demonstrate that in B-lymphocytes, IAP/CD47 may transduce
      the signals to activate the migratory activity, in which CDC42 may be
      specifically involved, and that IAP/CD47 shows synergistic effect with
      alpha4beta1 on B-cell migration. These findings would provide new insight into
      the role of IAP/CD47 on B-cell function.

PMID- 10891457
TI  - T-cell progenitor function during progressive human immunodeficiency virus-1
      infection and after antiretroviral therapy.
AB  - Impairment of T-cell renewal has been proposed as contributing to CD4(+) T-cell
      depletion in persons infected with human immunodeficiency virus-1. We analyzed
      the T-cell development capacity of progenitors using fetal thymus organ culture.
      Those who progressed to AIDS had a dramatic loss in T-cell development capacity
      shortly after seroconversion. In contrast, long-term nonprogressors retained
      progenitor capacity 8 years after seroconversion. Approximately 70% of patients
      experienced an improvement in T-cell development capacity after receiving 6
      months of potent antiretroviral therapy. Improvement in T-cell development in
      fetal thymus organ culture correlated with an increase in the number of naive
      CD4(+) T cells in peripheral blood. Numbers of progenitors in blood and bone
      marrow after seroconversion or during therapy did not correlate with the change
      observed in T-cell development capacity. These data provide evidence that HIV-1
      infection can interfere with T-cell renewal at the level of the progenitor cell.
      Interference with T-cell renewal may contribute to CD4(+) T-cell depletion.

PMID- 10891458
TI  - HIV protease inhibitors restore impaired T-cell proliferative response in vivo
      and in vitro: a viral-suppression-independent mechanism.
AB  - In 99 adults infected with human immunodeficiency virus type 1 (HIV-1) who
      received highly active antiretroviral therapy (HAART) (including 2 nucleoside
      analogues and 1 or 2 protease inhibitors) for 1 year, CD4(+) and CD8(+) T cells
      (including memory and naive subsets) increased similarly among patients with
      sustained plasma viral load decrease, transient decrease, or no decrease. A
      linear correlation was observed between the decrease in serum beta(2)
      microglobulin concentration (an independent surrogate marker of HIV disease) and
      the increase in peripheral blood T-cells (CD4(+) and CD8(+)) counts. In vitro,
      HIV protease inhibitors indinavir and saquinavir (but not nucleoside analogues)
      enhanced the survival of patients' peripheral blood T cells at doses that are at
      least 30-fold lower than those required for achieving 90% viral inhibition in the
      same cultures. This enhanced T-cell survival (which is similar for CD4 and CD8
      cells) was associated with a restoration of T-cell proliferative response to
      immune stimuli. However, neither TCR/CD3-ligation- nor Fas-ligation-triggered
      apoptosis was affected by either of the 2 protease inhibitors. A reduction in
      apoptosis observed after prolonged culture of patient T cells in the presence of
      the protease inhibitors could result from restored T-cell proliferation. These
      findings explain the discrepancies between virologic and immunologic responses
      that are increasingly reported in patients receiving HAART, and may provide
      insights into the pathogenesis of HIV infection.

PMID- 10891459
TI  - Overexpression of murine fizzy-related (fzr) increases natural killer cell
      mediated cell death and suppresses tumor growth.
AB  - Fizzy-related (fzr) is a recently identified 7WD domain family member implicated
      in cell cycle regulation of Drosophila and yeast. In this study, the murine
      homologue of fzr was isolated by suppression subtractive hybridization as a gene
      with decreased expression during malignant progression of a murine B-lymphoma
      cell line. Retroviral overexpression of fzr in B-lymphoma cells reduced tumor
      formation. Those tumors that did arise had diminished or extinguished retroviral
      Fzr. Surprisingly, fzr overexpression dramatically increased B-lymphoma cell
      susceptibility to natural killer cell (NK) cytotoxicity, a host-resistant
      mechanism for tumor formation in this model system. These findings implicate fzr
      as a new category of genes suppressing B-cell tumorigenesis and suggest a novel
      role for fzr in the target cell interaction with NK cells.

PMID- 10891460
TI  - Detection of clonotypic IGH and TCR rearrangements in the neonatal blood spots of
      infants and children with B-cell precursor acute lymphoblastic leukemia.
AB  - An attractive hypothesis is that in utero exposure of hematopoietic cells to
      oncogenic agents can induce molecular changes leading to overt acute
      lymphoblastic leukemia (ALL) in infants and perhaps older children as well.
      Although supported by studies of identical infant twins with concordant leukemia,
      and of nontwined patients with MLL gene rearrangements, this concept has not been
      extended to the larger population of B-lineage ALL patients who lack unique
      nonconstitutive mutations or abnormally rearranged genes. We therefore sought to
      demonstrate a prenatal origin for 7 cases of B-cell precursor ALL (either CD10(+)
      or CD10(-)) that had been diagnosed in infants and children 14 days to 9 years of
      age. Using a polymerase chain reaction-based assay, we identified the same
      clonotypic immunoglobulin heavy-chain complementarity determining region or T
      cell receptor V(D)2-D(D)3 sequences in the neonatal blood spots (Guthrie card)
      and leukemic cell DNAs of 2 infants with CD10(-) ALL and 2 of the 5 older
      patients with CD10(+) ALL. Nucleotide sequencing showed a paucity of N or P
      regions and shortened D germ line and conserved J sequences, indicative of cells
      arising from fetal hematopoiesis. Our findings strongly suggest a prenatal origin
      for some cases of B-cell precursor ALL lacking specific clonotypic abnormalities.

PMID- 10891461
TI  - Deregulation of the ubiquitin system and p53 proteolysis modify the apoptotic
      response in B-CLL lymphocytes.
AB  - We recently reported increased sensitivity of B-cell chronic lymphocytic leukemia
      (B-CLL) lymphocytes to apoptotic death activation by the proteasome-specific
      inhibitor lactacystin. Here, we show that only specific-not nonspecific
      proteasomal inhibitors can discriminate between malignant and normal lymphocytes
      in inducing the apoptotic death response. Indeed, lactacystin and its active
      metabolite clasto-lactacystin beta-lactone induced apoptotic death in CLL but not
      in normal lymphocytes. This difference was completely abolished when tripeptide
      aldehydes such as MG132 or LLnL (which can also inhibit calpains) were used as
      less specific proteasomal inhibitors. Moreover, B-CLL cells exhibited a
      constitutive altered ubiquitin-proteasome system, including a threefold higher
      chymotrypsin-like proteasomal activity and high levels of nuclear ubiquitin
      conjugated proteins compared with normal lymphocytes. Interestingly, B-CLL cells
      also displayed altered proteolytic regulation of wild-type p53, an apoptotic
      factor reported to be a substrate for the ubiquitin-proteasome system. Nuclear
      wild-type p53 accumulated after lactacystin treatment used at the discriminating
      concentration in malignant, but not in normal, lymphocytes. In contrast, p53 was
      stabilized by MG132 or LLnL in malignant and normal cells undergoing apoptosis,
      indicating that in normal lymphocytes p53 is regulated mainly by calpains and not
      by the ubiquitin-proteasome system. This work raises the possibility that two
      different proteolytic pathways controlling p53 stability may be pathologically
      imbalanced. This could result in modification of apoptosis control, since in CLL
      lymphocytes a highly upregulated ubiquitin-proteasome system, which controls p53
      stability among other apoptotic factors, was correlated with an increased
      propensity of these cells to apoptosis triggered by lactacystin.

PMID- 10891462
TI  - Bcl-X(L) is up-regulated by HTLV-I and HTLV-II in vitro and in ex vivo ATLL
      samples.
AB  - Human T lymphotropic virus type I (HTLV-I) is the etiological agent of adult T
      cell lymphocytic leukemia (ATLL), whereas HTLV-II has not been associated with
      hematopoietic malignancies. The control of apoptotic pathways has emerged as a
      critical step in the development of many cancer types. As a result, the
      underlying mechanism of long-term survival of HTLV-I and HTLV-II was studied in
      infected T cells in vitro and in ex vivo ATLL samples. Results indicate that HTLV
      I- and HTLV-II-infected T cells in vitro express high levels of the antiapoptotic
      protein Bcl compared with other human leukemic T cell lines or uninfected
      peripheral blood mononuclear cells. The levels of proapoptotic proteins Bax, BAD,
      and Bak were not significantly altered. HTLV-I and HTLV-II viral transactivators,
      Tax1 and Tax2, are known to increase expression of cellular genes. These proteins
      were tested for increased transcription from the human Bcl2 and Bcl-X(L)
      promoters. Whereas no effect was observed on the Bcl2 promoter, both Tax1 and
      Tax2 increased transcription of the Bcl-X(L) promoter in T cells, although Tax1
      appeared to be more efficient than Tax2. The biological significance of these
      observations was validated by the finding of an increased expression of Bcl-X(L)
      in ex vivo ATLL cells, especially from patients unresponsive to various
      chemotherapy regimens. Altogether, these data suggest that overexpression of Bcl
      X(L )in vivo( )may be in part responsible for the resistance of ATLL cells to
      chemotherapy. In addition, inefficient activation of the Bcl-X(L) promoter by
      Tax2 may result in a shorter survival time of HTLV-II-infected cells in vivo and
      a diminished risk of leukemia development.

PMID- 10891463
TI  - Endostatin, an antiangiogenic drug, induces tumor stabilization after
      chemotherapy or anti-CD20 therapy in a NOD/SCID mouse model of human high-grade
      non-Hodgkin lymphoma.
AB  - Both chemotherapy and chimeric anti-CD20 monoclonal antibodies are effective
      agents against B-cell non-Hodgkin lymphoma (NHL). However, patients achieving
      remission are at risk of relapse. To evaluate the effect of the antiangiogenic
      drug endostatin used alone and after the administration of cyclophosphamide (CTX)
      or the anti-CD20 antibody rituximab, we generated a new model of human NHL by
      transplanting Namalwa cells intraperitoneally into nonobese diabetic/severe
      combined immunodeficient (NOD/SCID) mice. First, we determined the most effective
      treatment schedule for the drugs assessed. When administered alone, CTX (3
      courses of 75 mg/kg of body weight given intraperitoneally), rituximab (3 courses
      of 25 mg/kg given intraperitoneally), and endostatin (5 courses of 50 microg
      given subcutaneously) delayed tumor growth, and CTX was the most effective in
      controlling bulky disease. When given after chemotherapy or immunotherapy,
      endostatin effectively induced tumor stabilization. When mice given CTX or
      rituximab on days 3, 5, and 7 after transplantation were randomly assigned to
      receive endostatin or phosphate-buffered saline on days 15 to 19, tumor growth
      was prevented in endostatin-treated mice as long as the drug was administered.
      Furthermore, administration of endostatin on days 25 to 29 after tumor regrowth
      still induced significant tumor regression, whereas CTX and rituximab were not
      effective. The specific antiangiogenic action of endostatin was confirmed by in
      vitro and in vivo studies indicating that the drug inhibited proliferation and
      induced apoptosis of endothelial (but not of NHL) cells. In conclusion,
      sequential administration of chemotherapy and endostatin seems promising for
      treating bulky NHL, and the less toxic sequential administration of rituximab and
      endostatin is promising for treating limited disease. (

PMID- 10891464
TI  - AML1-MTG8 leukemic protein induces the expression of granulocyte colony
      stimulating factor (G-CSF) receptor through the up-regulation of CCAAT/enhancer
      binding protein epsilon.
AB  - The t(8;21) translocation is one of the most frequent chromosomal abnormalities
      associated with acute myeloid leukemia (AML). In this translocation, the AML1
      (CBFA2/PEBP2aB) gene is disrupted and fused to the MTG8 (ETO) gene. The ectopic
      expression of the resulting AML1-MTG8 fusion gene product in L-G and 32Dcl3
      murine myeloid precursor cells stimulates cell proliferation without inducing
      morphologic terminal differentiation into mature granulocytes in response to
      granulocyte-colony stimulating factor (G-CSF). This study found that the ectopic
      expression of AML1-MTG8 elevates the expression of the G-CSF receptor (G-CSFR).
      Analysis of the promoter region of the G-CSFR gene revealed that up-regulation of
      G-CSFR expression by AML1-MTG8 does not depend on the AML1-binding sequence, but
      on the C/EBP (CCAAT/enhancer binding protein) binding site. The results suggest
      that the overproduction of G-CSFR is at least partly mediated by C/EBPepsilon,
      whose expression is activated by AML1-MTG8. The ectopic expression of G-CSFR in L
      G cells induced cell proliferation in response to G-CSF, but did not inhibit cell
      differentiation into mature neutrophils. Overexpression of C/EBPepsilon in L-G
      cells also stimulated G-CSF-dependent cell proliferation. High expression levels
      of G-CSFR were also found in the leukemic cells of AML patients with t(8;21).
      Therefore, G-CSF-dependent cell proliferation of myeloid precursor cells may be
      implicated in leukemogenesis.

PMID- 10891465
TI  - Inhibition of in vitro spontaneous apoptosis by IL-7 correlates with bcl-2 up
      regulation, cortical/mature immunophenotype, and better early cytoreduction of
      childhood T-cell acute lymphoblastic leukemia.
AB  - In normal T-cell development, IL-7 plays a nonredundant role as an antiapoptic
      factor by regulating Bcl-2 expression in pro-T cells. In the current study, we
      addressed the roles of IL-7 and related cytokines as apoptosis-modulating factors
      in precursor T-cell acute lymphoblastic leukemia (T-ALL). To this end, leukemic
      blasts from pediatric patients with T-ALL were prospectively investigated as to
      their responsiveness to IL-7, IL-4, and IL-2 (in terms of modulation of
      spontaneous apoptosis, assessed by flow cytometry), cytokine receptor expression
      profiles, and expression levels of Bcl-2 and Bax proteins. IL-7, in contrast to
      IL-4 and IL-2, was highly efficient in apoptosis inhibition, and this effect
      correlated with the expression levels of IL-7Ralpha chain and with the up
      regulation of Bcl-2 protein expression (P <.0001). Subclassification of T-ALL
      samples (n = 130) according to their in vitro IL-7 responses revealed that IL-7
      refractory samples were more frequently positive for CD34 (P <.0001) and the
      myeloid-associated antigen CD33 (P =.01), whereas IL-7 responsiveness was
      associated with an expression of more mature differentiation-associated T-cell
      antigens (CD1a, surface CD3, CD4/8; P <.05). Furthermore, the extent of apoptosis
      inhibition by IL-7 in vitro quantitatively correlated with early cytoreduction as
      determined by the prednisone peripheral blood response on day 8 and cytoreduction
      in the marrow on day 15 (n = 87; P <.05). Multivariate analysis of the apoptosis
      related parameters investigated, including spontaneous apoptosis, its inhibition
      by IL-7, and expression levels of Bcl-2 and Bax, showed that only IL-7
      responsiveness has an independent impact on early cytoreduction (P <. 05), thus
      indicating a potential prognostic relevance of IL-7 sensitivity in T-ALL.

PMID- 10891466
TI  - Oxidative stress interferes with cancer chemotherapy: inhibition of lymphoma cell
      apoptosis and phagocytosis.
AB  - Many antineoplastic drugs kill tumor cells by inducing apoptosis. This highly
      controlled mechanism of cell death is thought to be physiologically advantageous
      because apoptotic cells are removed by phagocytosis before they lose their
      permeability barrier, thus preventing induction of an inflammatory response to
      the dying cells. In contrast, necrotic cells lyse and release their contents into
      the extracellular space, thus inducing inflammation. In this report, we examine
      the effects of oxidative stress on chemotherapy-induced cell killing. We find
      that H(2)O(2) inhibits the ability of 4 different chemotherapy drugs (VP-16,
      doxorubicin, cisplatin, and AraC) to induce apoptosis in human Burkitt lymphoma
      cells. H(2)O(2) shifts the form of cell death from apoptosis to
      pyknosis/necrosis, which occurs after a significant delay compared with
      chemotherapy-induced apoptosis. It can also lower the degree of cell killing by
      these drugs. These effects of H(2)O(2) can be prevented by the antioxidant agents
      Desferal, Tempol, and dimethylsulfoxide. Phagocytosis by monocyte-derived
      macrophages of VP-16-treated lymphoma cells is also inhibited by H(2)O(2). Cells
      killed with H(2)O(2) (with or without VP-16) do ultimately undergo phagocytosis,
      but this occurs only after they have lost their permeability barrier. Thus,
      membrane-intact apoptotic cells are recognized and phagocytosed by monocyte
      derived macrophages, but membrane-intact pyknotic/necrotic cells are not. The
      results suggest that chemotherapy-induced apoptosis and phagocytosis of cancer
      cells may be enhanced by including certain antioxidant agents in the treatment
      protocol.

PMID- 10891467
TI  - Reperfusion injury pathophysiology in sickle transgenic mice.
AB  - Reperfusion of tissues after interruption of their vascular supply causes free
      radical generation that leads to tissue damage, a scenario referred to as
      "reperfusion injury." Because sickle disease involves repeated transient ischemic
      episodes, we sought evidence for excessive free-radical generation in sickle
      transgenic mice. Compared with normal mice, sickle mice at ambient air had a
      higher ethane excretion (marker of lipid peroxidation) and greater conversion of
      salicylic acid to 2,3-dihydroxybenzoic acid (marker of hydroxyl radical
      generation). During hypoxia (11% O(2)), only sickle mice converted tissue
      xanthine dehydrogenase to oxidase. Only the sickle mice exhibited a further
      increase in ethane excretion during restitution of normal oxygen tension after 2
      hours of hypoxia. Only the sickle mice showed abnormal activation of nuclear
      factor-kappaB after exposure to hypoxia-reoxygenation. Allopurinol, a potential
      therapeutic agent, decreased ethane excretion in the sickle mice. Thus, sickle
      transgenic mice exhibit biochemical footprints consistent with excessive free
      radical generation even at ambient air and following a transient induction of
      enhanced sickling. We suggest that reperfusion injury physiology may contribute
      to the evolution of the chronic organ damage characteristic of sickle cell
      disease. If so, novel therapeutic approaches might be of value.

PMID- 10891468
TI  - Novel in vitro assay for the detection of pharmacologic inducers of fetal
      hemoglobin.
AB  - Current techniques for identifying fetal hemoglobin (HbF) inducers are complex
      and time consuming. We developed a rapid and efficient method for detecting HbF
      inducers. Our system uses a recombinant DNA construct in which the coding
      sequences of 2 different luciferase reporter genes, firefly and renilla, are
      substituted for those of human gamma and beta globin genes, respectively. The
      activity of these genes can be distinguished by a simple, highly sensitive
      enzymatic assay in cell lysates. GM979 cells stably transfected with the
      construct are cultured in the presence of compounds, and their effects are
      determined by measuring the changes in activity of the 2 luciferase genes.
      Specific gamma globin gene inducers are recognized by their ability to increase
      gamma-firefly luciferase (gamma(F)) gene activity significantly more than beta
      renilla luciferase (beta(R)) gene activity, identified by an increased ratio of
      gamma-firefly luciferase activity over total luciferase activity. These results
      suggest that the use of the 2 luciferase reporter genes provides a simple, highly
      sensitive, and reproducible system for the detection of compounds that increase
      gamma-globin gene expression. It can therefore be used for the screening of
      chemical agents that may have gamma-globin gene inducibility.

PMID- 10891469
TI  - Sulfated glycoconjugates enhance CD36-dependent adhesion of Plasmodium falciparum
      infected erythrocytes to human microvascular endothelial cells.
AB  - A novel adhesive pathway that enhances the adhesion of Plasmodium falciparum
      infected erythrocytes (IEs) to endothelial cells has been identified. The
      sulfated glycoconjugates heparin, fucoidan, dextran sulfate 5000, and dextran
      sulfate 500 000 caused a dramatic increase in adhesion of IEs to human dermal
      microvascular endothelial cells. The same sulfated glycoconjugates had little
      effect on IE adhesion to human umbilical vein endothelial cells, a CD36-negative
      cell line. The effect was abolished by a monoclonal antibody directed against
      CD36, suggesting that enhanced adhesion to endothelium is dependent on CD36. No
      effect was observed on adhesion to purified platelet CD36 cells immobilized on
      plastic. The same sulfated glycoconjugates enhanced adhesion of infected
      erythrocytes to COS cells transfected with CD36, and this was inhibited by the
      CD36 monoclonal antibody. These findings demonstrate a role for sulfated
      glycoconjugates in endothelial adherence that may be important in determining the
      location and magnitude of sequestration through endogenous carbohydrates. In
      addition, they highlight possible difficulties that may be encountered from the
      proposed use of sulfated glycoconjugates as antiadhesive agents in patients with
      severe malaria.

PMID- 10891470
TI  - Direct interaction of NF-E2 with hypersensitive site 2 of the beta-globin locus
      control region in living cells.
AB  - The human beta-globin locus control region (LCR) confers high-level, tissue
      specific expression to the beta-globin genes. Tandem Maf recognition elements
      (MAREs) within the hypersensitive site 2 (HS2) subregion of the LCR are important
      for the strong enhancer activity of the LCR. Multiple proteins are capable of
      interacting with these sites in vitro, including the erythroid cell- and
      megakaryocyte-specific transcription factor, NF-E2. The importance of NF-E2 for
      beta-globin gene expression is evident in murine erythroleukemia cells lacking
      the p45 subunit of NF-E2. These CB3 cells have a severe defect in alpha- and beta
      globin gene transcription, which can be restored by expression of NF-E2. However,
      mice nullizygous for p45 express nearly normal levels of beta-globin. Thus,
      either a redundant factor(s) exists in mice that can functionally replace NF-E2,
      or NF-E2 does not function through the LCR to regulate beta-globin gene
      expression. To address this issue, we asked whether NF-E2 binds directly to the
      tandem MAREs of HS2 in intact cells. Using a chromatin immunoprecipitation assay,
      we provide evidence for NF-E2 binding directly and specifically to HS2 in living
      erythroleukemia cells and in mouse fetal liver. The specific immunoisolation of
      HS2 sequences was dependent on the presence of p45 and on intact MAREs within
      HS2. These results support a direct role for NF-E2 in the regulation of beta
      globin gene expression through activation of the LCR.

PMID- 10891471
TI  - Expression of Kell blood group protein in nonerythroid tissues.
AB  - The Kell blood group protein is a zinc endopeptidase that yields endothelin-3, a
      potent bioactive peptide, by cleavage of big endothelin-3, a larger intermediate
      precursor. On red cells, Kell protein is linked by a single disulfide bond to XK,
      a protein that traverses the membrane 10 times and whose absence, as occurs in
      the McLeod phenotype, is associated with a set of clinical symptoms that include
      nerve and muscle disorders and red cell acanthocytosis. Previous studies
      indicated that Kell is primarily expressed in erythroid tissues, whereas XK has a
      wider tissue distribution. The tissue distribution of Kell protein has been
      further investigated by Northern blot analysis, PCR-screening of tissue
      complementary DNAs (cDNAs), and Western immunoblots. Screening of an RNA dot-blot
      panel confirmed that Kell is primarily expressed in erythroid tissues but is also
      expressed in a near equal amount in testis, with weaker expression in a large
      number of other tissues. PCR-screening of cDNAs from different tissues and DNA
      sequencing of the products gave similar results. In 2 of the nonerythroid tissues
      tested, testis and skeletal muscle, Kell protein was detected by Western
      immunoblotting. In skeletal muscle, isolation of XK with a specific antibody
      coisolated Kell protein. These studies demonstrate that Kell is expressed in both
      erythroid and nonerythroid tissues and is associated with XK.

PMID- 10891472
TI  - Thymic atrophy in murine acute graft-versus-host disease is effected by impaired
      cell cycle progression of host pro-T and pre-T cells.
AB  - Reconstitution of the peripheral T-cell compartment is a critical aspect for the
      success of bone marrow transplantation and is also dependent on the
      reestablishment of normal thymic structure and function. Graft-versus-host
      disease (GVHD), however, exacerbates posttransplant immunodeficiency through a
      deleterious effect on thymic function. To investigate the mechanisms of GVHD
      mediated thymic disease, 2 murine parent-->F(1 )transplantation models of acute
      and chronic GVHD, respectively, were studied. Acute GVHD was associated with
      changes in thymic architecture and a reduction in cellularity mainly because of
      the decrease in CD4(+)CD8(+), or double-positive (DP) thymocytes, to less than
      15% of values found in mice without GVHD. Simultaneously, mature donor-derived T
      cells expanded in the confines of the allogeneic thymic microenvironment, leading
      to local inflammation. Through analysis of in vivo cell proliferation, we
      demonstrated that the ensuing depletion of DP thymocytes was secondary to a
      decreased commitment of resident pro-T and pre-T cells to enter the cell cycle.
      Moreover, DP cells themselves showed altered proliferative capacities in the
      presence of acute GVHD. These findings suggested that thymic atrophy in acute
      GVHD is effected by impaired cellular proliferation of immature host thymocytes
      and that the failure of these cells to enter the cell cycle is dependent on an
      interferon (IFN)-gamma-driven immune response. In contrast, interleukin-4-driven
      chronic GVHD was not accompanied by a sustained thymic infiltration of donor T
      cells. Consequently, there was a lack of apparent structural changes, a
      restricted in situ transcription of inflammatory cytokines, and a virtually
      unchanged cell cycle progression in vivo.

PMID- 10891473
TI  - Molecular monitoring of minimal residual disease in patients in long-term
      complete remission after allogeneic stem cell transplantation for multiple
      myeloma.
AB  - In the present study, we used a polymerase chain reaction-based (PCR-based)
      strategy to retrospectively analyze the presence of residual myeloma cells in
      serial posttransplant bone marrow samples obtained from 13 patients in remission
      after allogeneic hemopoietic stem cell transplantation (allo SCT). For this
      purpose, patient-specific primers were generated from complementarity determining
      regions 2 and 3 of the rearranged IgH gene. The level of sensitivity of the PCR
      based assay ranged from 1 in 10(5) to 1 in 10(6) normal marrow cells. Following
      transplantation, 9 of 12 patients who attained stringently defined complete
      remission (CR) remained persistently PCR(-) for a median of 36 months, and 4 of
      the patients remained PCR(-) up to the latest analysis, which was performed at
      48, 72, 72, and 120 months, respectively, after allo SCT. None of the patients in
      the PCR(-) subgroup experienced a disease relapse, and only 1 of 4 PCR(+)
      patients experienced a relapse. It is concluded that allo SCT has the potential
      ability to induce sustained serological and molecular CR in selected patients
      with multiple myeloma.

PMID- 10891474
TI  - Telomere length shortening in chronic myelogenous leukemia is associated with
      reduced time to accelerated phase.
AB  - Telomere shortening is associated with disease evolution in chronic myelogenous
      leukemia (CML). We have examined the relationship between diagnostic telomere
      length and outcome in 59 patients with CML who entered into the MRC CMLIII Trial
      by Southern blot hybridization using the (TTAGGG)(4) probe. Age-adjusted telomere
      repeat array (TRA) reduction was found to significantly correlate with time from
      diagnosis to acceleration, such that patients with a larger TRA reduction entered
      the accelerated phase more rapidly (r = -0.50; P =.008). Cox-regression analysis
      for this group was suggestive of a relationship between a greater TRA-reduction
      and a shorter time to acceleration (P =.054). Age-adjusted TRA reduction did not
      significantly affect either the time to blast crisis or overall survival. Our
      results show that telomere shortening observed at the time of diagnosis in CML
      significantly influences the time to progress to the accelerated phase. The
      measurement of diagnostic TRA may prove to be clinically important in the
      selection of patients at high risk of disease transformation in CML.

PMID- 10891475
TI  - ESOP-1, a secreted protein expressed in the hematopoietic, nervous, and
      reproductive systems of embryonic and adult mice.
AB  - To isolate soluble factors expressed in early phases of hematopoietic
      differentiation, we applied the signal sequence trap method to the in vitro
      murine hematopoietic differentiation system, in which ES cells are cocultured
      with OP-9 stroma cells. This strategy allowed us to isolate cDNA for a secreted
      protein, ESOP-1, of 160 amino acids, the sequence of which shows 64% identity
      with human ESOP-1/MD-2. ESOP-1 mRNA was highly expressed in the mouse embryos at
      7.5 days after coitus. Expression of the ESOP-1 mRNA and protein was shown in the
      embryonic and adult hematopoietic system. In addition, the ESOP-1 protein was
      found in the yolk sac-blood islands, the developing nervous system, and the adult
      reproductive system. These results suggest that ESOP-1 may play some roles in the
      development or maintenance of hematopoietic, nervous, and reproductive systems.

PMID- 10891476
TI  - Expression of breast cancer resistance protein in blast cells from patients with
      acute leukemia.
AB  - Breast cancer resistance protein (BCRP) is a novel member of the adenosine
      triphosphate-binding cassette superfamily of transport proteins. Transfection and
      enforced expression of BCRP in drug-sensitive cells confer resistance to
      mitoxantrone, doxorubicin, daunorubicin, and topotecan. We studied blast cells
      from 21 acute leukemia patients (20 acute myeloid leukemia, 1 acute lymphocytic
      leukemia) for the expression of BCRP mRNA using a quantitative reverse
      transcription polymerase chain reaction assay. BCRP mRNA expression varied more
      than 1000-fold among the samples tested, with low or barely detectable expression
      in half of the samples. Seven samples (33%) had relatively high expression of
      BCRP mRNA. High expression of BCRP did not correlate strongly with high
      expression of P-glycoprotein, suggesting that BCRP may cause resistance to
      certain antileukemic drugs in P-glycoprotein-negative cases. High expression of
      BCRP mRNA is sufficiently frequent in AML to warrant more extensive
      investigations to determine the relation of disease subtype and treatment outcome
      to BCRP expression and function.

PMID- 10891477
TI  - Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell
      response under suboptimal costimulatory conditions.
AB  - CD37 is a membrane protein of the tetraspanin superfamily, which includes CD9,
      CD53, CD63, CD81, and CD82. Many of these molecules are expressed on leukocytes
      and have been implicated in signal transduction, cell-cell interactions, and
      cellular activation and development. We generated and analyzed mice deficient for
      CD37. Despite the high expression of CD37 on cells of the immune system, no
      changes in development and cellular composition of lymphoid organs were observed
      in mice lacking CD37. Analyses of humoral immune responses revealed a reduced
      level of immunoglobulin G1 (IgG1) in the sera of nonimmunized mice and an
      alteration of responses to T-cell-dependent antigens. Antibody responses to model
      antigen administered in the absence of adjuvant and to viral infections were
      generally poor in CD37-deficient mice. These poor antibody responses could be
      overcome by the immunization of antigen together with adjuvant. These results
      suggest a role for CD37 in T-cell-B-cell interactions which manifests itself
      under suboptimal costimulatory conditions.

PMID- 10891478
TI  - Role for Lyn tyrosine kinase as a regulator of stress-activated protein kinase
      activity in response to DNA damage.
AB  - The cellular response to DNA damage includes activation of the nuclear Lyn
      protein tyrosine kinase. Using cells deficient in Lyn expression, the present
      studies demonstrate that Lyn is required in part for induction of the stress
      activated protein kinase (SAPK) in the response to 1-beta-D
      arabinofuranosylcytosine (ara-C) and other genotoxic agents. By contrast,
      exposure of Lyn-deficient cells to ara-C, ionizing radiation, or cisplatin had no
      effect on activation of extracellular signal-regulated protein kinase or p38
      mitogen-activated protein kinase. Similar findings were obtained in cells stably
      expressing a kinase-inactive, dominant-negative Lyn(K-R) mutant. Coexpression
      studies demonstrate that Lyn, but not Lyn(K-R), induces SAPK activity. In
      addition, the results demonstrate that Lyn activates SAPK by an MKK7-dependent,
      SEK1-independent mechanism. As MEKK1 functions upstream to MKK7 and SAPK, the
      finding that a dominant-negative MEKK1(K-M) mutant blocks Lyn-induced SAPK
      activity supports involvement of the MEKK1-->MKK7 pathway. The results also
      demonstrate that inhibition of Lyn-induced SAPK activity abrogates the apoptotic
      response of cells to genotoxic stress. These findings indicate that activation of
      SAPK by DNA damage is mediated in part by Lyn and that the Lyn-->MEKK1-->MKK7-
      >SAPK pathway is functional in the induction of apoptosis by genotoxic agents.

PMID- 10891479
TI  - Role of the IkappaB kinase complex in oncogenic Ras- and Raf-mediated
      transformation of rat liver epithelial cells.
AB  - NF-kappaB/Rel factors have been implicated in the regulation of liver cell death
      during development, after partial hepatectomy, and in hepatocytes in culture. Rat
      liver epithelial cells (RLEs) display many biochemical and ultrastructural
      characteristics of oval cells, which are multipotent cells that can differentiate
      into mature hepatocytes. While untransformed RLEs undergo growth arrest and
      apoptosis in response to transforming growth factor beta1 (TGF-beta1) treatment,
      oncogenic Ras- or Raf-transformed RLEs are insensitive to TGF-beta1-mediated
      growth arrest. Here we have tested the hypothesis that Ras- or Raf-transformed
      RLEs have altered NF-kappaB regulation, leading to this resistance to TGF-beta1.
      We show that classical NF-kappaB is aberrantly activated in Ras- or Raf
      transformed RLEs, due to increased phosphorylation and degradation of IkappaB
      alpha protein. Inhibition of NF-kappaB activity with a dominant negative form of
      IkappaB-alpha restored TGF-beta1-mediated cell killing of transformed RLEs. IKK
      activity mediates this hyperphosphorylation of IkappaB-alpha protein. As judged
      by kinase assays and transfection of dominant negative IKK-1 and IKK-2 expression
      vectors, NF-kappaB activation by Ras appeared to be mediated by both IKK-1 and
      IKK-2, while Raf-induced NF-kappaB activation was mediated by IKK-2. NF-kappaB
      activation in the Ras-transformed cells was mediated by both the Raf and
      phosphatidylinositol 3-kinase pathways, while in the Raf-transformed cells, NF
      kappaB induction was mediated by the mitogen-activated protein kinase cascade.
      Last, inhibition of either IKK-1 or IKK-2 reduced focus-forming activity in Ras
      transformed RLEs. Overall, these studies elucidate a mechanism that contributes
      to the process of transformation of liver cells by oncogene Ras and Raf through
      the IkappaB kinase complex leading to constitutive activation of NF-kappaB.

PMID- 10891480
TI  - Different protein kinase C isoforms determine growth factor specificity in
      neuronal cells.
AB  - Although mitogenic and differentiating factors often activate a number of common
      signaling pathways, the mechanisms leading to their distinct cellular outcomes
      have not been elucidated. In a previous report, we demonstrated that mitogen
      activated protein (MAP) kinase (ERK) activation by the neurogenic agents
      fibroblast growth factor (FGF) and nerve growth factor is dependent on protein
      kinase Cdelta (PKCdelta), whereas MAP kinase activation in response to the
      mitogen epidermal growth factor (EGF) is independent of PKCdelta in rat
      hippocampal (H19-7) and pheochromocytoma (PC12) cells. We now show that EGF
      activates MAP kinase through a PKCzeta-dependent pathway involving
      phosphatidylinositol 3-kinase and PDK1 in H19-7 cells. PKCzeta, like PKCdelta,
      acts upstream of MEK, and PKCzeta can potentiate Raf-1 activation by EGF.
      Inhibition of PKCzeta also blocks EGF-induced DNA synthesis as monitored by
      bromodeoxyuridine incorporation in H19-7 cells. Finally, in embryonic rat brain
      hippocampal cell cultures, inhibitors of PKCzeta or PKCdelta suppress MAP kinase
      activation by EGF or FGF, respectively, indicating that these factors activate
      distinct signaling pathways in primary as well as immortalized neural cells.
      Taken together, these results implicate different PKC isoforms as determinants of
      growth factor signaling specificity within the same cell. Furthermore, these data
      provide a mechanism whereby different growth factors can differentially activate
      a common signaling intermediate and thereby generate biological diversity.

PMID- 10891481
TI  - Stimulation of mitotic recombination events by high levels of RNA polymerase II
      transcription in yeast.
AB  - The impact of high levels of RNA polymerase II transcription on mitotic
      recombination was examined using lys2 recombination substrates positioned on
      nonhomologous chromosomes. Substrates were used that could produce Lys(+)
      recombinants by either a simple (noncrossover) gene conversion event or a
      crossover-associated recombination event, by only a simple gene conversion event,
      or by only a crossover event. Transcription of the lys2 substrates was regulated
      by the highly inducible GAL1-10 promoter or the low-level LYS2 promoter, with
      GAL1-10 promoter activity being controlled by the presence or absence of the
      Gal80p negative regulatory protein. Transcription was found to stimulate
      recombination in all assays used, but the level of stimulation varied depending
      on whether only one or both substrates were highly transcribed. In addition,
      there was an asymmetry in the types of recombination events observed when one
      substrate versus the other was highly transcribed. Finally, the lys2 substrates
      were positioned as direct repeats on the same chromosome and were found to
      exhibit a different recombinational response to high levels of transcription from
      that exhibited by the repeats on nonhomologous chromosomes. The relevance of
      these results to the mechanisms of transcription-associated recombination are
      discussed.

PMID- 10891482
TI  - Precursors to the U3 small nucleolar RNA lack small nucleolar RNP proteins but
      are stabilized by La binding.
AB  - Almost all small eukaryotic RNAs are processed from transiently stabilized 3'
      extended forms. A key question is how and why such intermediates are stabilized
      and how they can then be processed to the mature RNA. Here we report that yeast
      U3 is also processed from a 3'-extended precursor. The major 3'-extended forms of
      U3 (U3-3'I and -II) lack the cap trimethylation present in mature U3 and are not
      associated with small nucleolar RNP (snoRNP) proteins that bind mature U3, i.e.,
      Nop1p, Nop56p, and Nop58p. Depletion of Nop58p leads to the loss of mature U3 but
      increases the level of U3-3'I and -II, indicating a requirement for the snoRNP
      proteins for final maturation. Pre-U3 is cleaved by the endonuclease Rnt1p, but
      U3-3'I and -II do not extend to the Rnt1p cleavage sites. Rather, they terminate
      at poly(U) tracts, suggesting that they might be bound by Lhp1p (the yeast
      homologue of La). Immunoprecipitation of Lhp1p fused to Staphylococcus aureus
      protein A resulted in coprecipitation of both U3-3'I and -II. Deletion of LHP1,
      which is nonessential, led to the loss of U3-3'I and -II. We conclude that pre-U3
      is cleaved by Rnt1p, followed by exonuclease digestion to U3-3'I and -II. These
      species are stabilized against continued degradation by binding of Lhp1p.
      Displacement of Lhp1p by binding of the snoRNP proteins allows final maturation,
      which involves the exosome complex of 3'-->5' exonucleases.

PMID- 10891483
TI  - In vitro properties of the conserved mammalian protein hnRNP D suggest a role in
      telomere maintenance.
AB  - Mammalian chromosomes terminate with a 3' tail which consists of reiterations of
      the G-rich repeat, d(TTAGGG). The telomeric tail is the primer for replication by
      telomerase, and it may also invade telomeric duplex DNA to form terminal lariat
      structures, or T loops. Here we show that the ubiquitous and highly conserved
      mammalian protein hnRNP D interacts specifically with the G-rich strand of the
      telomeric repeat. A single gene encodes multiple isoforms of hnRNP D. All
      isoforms bind comparably to the G-rich strand, and certain isoforms can also bind
      tightly and specifically to the C-rich telomeric strand. G-rich telomeric
      sequences readily form structures stabilized by G-G pairing, which can interfere
      with telomere replication by telomerase. We show that hnRNP D binding to the G
      rich strand destabilizes intrastrand G-G pairing and that hnRNP D interacts
      specifically with telomerase in human cell extracts. This biochemical analysis
      suggest that hnRNP D could function in vivo to destabilize structures formed by
      telomeric G-rich tails and facilitate their extension by telomerase.

PMID- 10891484
TI  - Specific structural motifs determine TRAP220 interactions with nuclear hormone
      receptors.
AB  - The TRAP coactivator complex is a large, multisubunit complex of nuclear proteins
      which associates with nuclear hormone receptors (NRs) in the presence of cognate
      ligand and stimulates NR-mediated transcription. A single subunit, TRAP220, is
      thought to target the entire complex to a liganded receptor through a domain
      containing two of the signature LXXLL motifs shown previously in other types of
      coactivator proteins to be essential for mediating NR binding. In this work, we
      demonstrate that each of the two LXXLL-containing regions, termed receptor
      binding domains 1 and 2 (RBD-1 and RBD-2), is differentially preferred by
      specific NRs. The retinoid X receptor (RXR) displays a weak yet specific
      activation function 2 (AF2)-dependent preference for RBD-1, while the thyroid
      hormone receptor (TR), vitamin D(3) receptor (VDR), and peroxisome proliferator
      activated receptor all exhibit a strong AF2-dependent preference for RBD-2. Using
      site-directed mutagenesis, we show that preference for RBD-2 is due to the
      presence of basic-polar residues on the amino-terminal end of the core LXXLL
      motif. Furthermore, we show that the presence and proper spacing of both RBD-1
      and RBD-2 are required for an optimal association of TRAP220 with RXR-TR or RXR
      VDR heterodimers bound to DNA and for TRAP220 coactivator function. On the basis
      of these results, we suggest that a single molecule of TRAP220 can interact with
      both subunits of a DNA-bound NR heterodimer.

PMID- 10891485
TI  - Shared roles of yeast glycogen synthase kinase 3 family members in nitrogen
      responsive phosphorylation of meiotic regulator Ume6p.
AB  - Nitrogen limitation activates meiosis and meiotic gene expression in yeast, but
      nitrogen-responsive signal transduction mechanisms that govern meiotic gene
      expression are poorly understood. We show here that Ume6p, a subunit of the Ume6p
      Ime1p meiotic transcriptional activator, undergoes increased phosphorylation in
      vivo in response to nitrogen limitation. Phosphorylation depends on an N-terminal
      glycogen synthase kinase 3 (GSK3) target site in which substitutions cause
      reduced Ume6p-Ime1p interaction and meiotic gene expression, thus arguing that
      phosphorylation promotes functional Ume6p-Ime1p interaction. Phosphorylation of
      this site depends on two GSK3 homologs, Rim11p and Mck1p. Prior studies indicate
      that Rim11p phosphorylates both Ume6p and Ime1p in vitro and is required for
      Ume6p-Ime1p interaction, but no evidence has linked Mck1p function to Ume6p
      activity. Here we find that Mck1p-Ume6p interaction is detectable by two-hybrid
      assays and that meiosis in a partially defective rim11-K68R mutant is completely
      dependent on Mck1p. These findings argue that nitrogen limitation governs
      Rim11p/Mck1p-dependent phosphorylation of Ume6p, which in turn is required for
      Ume6p-Ime1p interaction and meiotic gene activation.

PMID- 10891486
TI  - BNIP3 and genetic control of necrosis-like cell death through the mitochondrial
      permeability transition pore.
AB  - Many apoptotic signaling pathways are directed to mitochondria, where they
      initiate the release of apoptogenic proteins and open the proposed mitochondrial
      permeability transition (PT) pore that ultimately results in the activation of
      the caspase proteases responsible for cell disassembly. BNIP3 (formerly NIP3) is
      a member of the Bcl-2 family that is expressed in mitochondria and induces
      apoptosis without a functional BH3 domain. We report that endogenous BNIP3 is
      loosely associated with mitochondrial membrane in normal tissue but fully
      integrates into the mitochondrial outer membrane with the N terminus in the
      cytoplasm and the C terminus in the membrane during induction of cell death.
      Surprisingly, BNIP3-mediated cell death is independent of Apaf-1, caspase
      activation, cytochrome c release, and nuclear translocation of apoptosis-inducing
      factor. However, cells transfected with BNIP3 exhibit early plasma membrane
      permeability, mitochondrial damage, extensive cytoplasmic vacuolation, and
      mitochondrial autophagy, yielding a morphotype that is typical of necrosis. These
      changes were accompanied by rapid and profound mitochondrial dysfunction
      characterized by opening of the mitochondrial PT pore, proton electrochemical
      gradient (Deltapsim) suppression, and increased reactive oxygen species
      production. The PT pore inhibitors cyclosporin A and bongkrekic acid blocked
      mitochondrial dysregulation and cell death. We propose that BNIP3 is a gene that
      mediates a necrosis-like cell death through PT pore opening and mitochondrial
      dysfunction.

PMID- 10891487
TI  - The T-cell receptor regulates Akt (protein kinase B) via a pathway involving Rac1
      and phosphatidylinositide 3-kinase.
AB  - The serine/threonine kinase Akt (also known as protein kinase B) (Akt/PKB) is
      activated upon T-cell antigen receptor (TCR) engagement or upon expression of an
      active form of phosphatidylinositide (PI) 3-kinase in T lymphocytes. Here we
      report that the small GTPase Rac1 is implicated in this pathway, connecting the
      receptor with the lipid kinase. We show that in Jurkat cells, activated forms of
      Rac1 or Cdc42, but not Rho, stimulate an increase in Akt/PKB activity. TCR
      induced Akt/PKB activation is inhibited either by PI 3-kinase inhibitors
      (LY294002 and wortmannin) or by overexpression of a dominant negative mutant of
      Rac1 but not Cdc42. Accordingly, triggering of the TCR rapidly stimulates a
      transient increase in GTP-Rac content in these cells. Similar to TCR stimulation,
      L61Rac-induced Akt/PKB kinase activity is also LY294002 and wortmannin sensitive.
      However, induction of Akt/PKB activity by constitutive active PI 3-kinase is
      unaffected when dominant negative Rac1 is coexpressed, placing Rac1 upstream of
      PI 3-kinase in the signaling pathway. When analyzing the signaling hierarchy in
      the pathway leading to cytoskeleton rearrangements, we found that Rac1 acts
      downstream of PI 3-kinase, a finding that is in accordance with numerous studies
      in fibroblasts. Our results reveal a previously unrecognized role of the GTPase
      Rac1, acting upstream of PI 3-kinase in linking the TCR to Akt/PKB. This is the
      first report of a membrane receptor employing Rac1 as a downstream transducer for
      Akt/PKB activation.

PMID- 10891488
TI  - Increased energy expenditure, decreased adiposity, and tissue-specific insulin
      sensitivity in protein-tyrosine phosphatase 1B-deficient mice.
AB  - Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine phosphatase
      that has been implicated in the regulation of insulin action, as well as in other
      signal transduction pathways. To investigate the role of PTP-1B in vivo, we
      generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B
      deficient mice have remarkably low adiposity and are protected from diet-induced
      obesity. Decreased adiposity is due to a marked reduction in fat cell mass
      without a decrease in adipocyte number. Leanness in PTP-1B-deficient mice is
      accompanied by increased basal metabolic rate and total energy expenditure,
      without marked alteration of uncoupling protein mRNA expression. In addition,
      insulin-stimulated whole-body glucose disposal is enhanced significantly in PTP
      1B-deficient animals, as shown by hyperinsulinemic-euglycemic clamp studies.
      Remarkably, increased insulin sensitivity in PTP-1B-deficient mice is tissue
      specific, as insulin-stimulated glucose uptake is elevated in skeletal muscle,
      whereas adipose tissue is unaffected. Our results identify PTP-1B as a major
      regulator of energy balance, insulin sensitivity, and body fat stores in vivo.

PMID- 10891489
TI  - HMG-I/Y, a new c-Myc target gene and potential oncogene.
AB  - The HMG-I/Y gene encodes the HMG-I and HMG-Y proteins, which function as
      architectural chromatin binding proteins important in the transcriptional
      regulation of several genes. Although increased expression of the HMG-I/Y
      proteins is associated with cellular proliferation, neoplastic transformation,
      and several human cancers, the role of these proteins in the pathogenesis of
      malignancy remains unclear. To better understand the role of these proteins in
      cell growth and transformation, we have been studying the regulation and function
      of HMG-I/Y. The HMG-I/Y promoter was cloned, sequenced, and subjected to
      mutagenesis analysis. A c-Myc-Max consensus DNA binding site was identified as an
      element important in the serum stimulation of HMG-I/Y. The oncoprotein c-Myc and
      its protein partner Max bind to this site in vitro and activate transcription in
      transfection experiments. HMG-I/Y expression is stimulated by c-Myc in a Myc
      estradiol receptor cell line in the presence of the protein synthesis inhibitor
      cycloheximide, indicating that HMG-I/Y is a direct c-Myc target gene. HMG-I/Y
      induction is decreased in Myc-deficient fibroblasts. HMG-I/Y protein expression
      is also increased in Burkitt's lymphoma cell lines, which are known to have
      increased c-Myc protein. Like Myc, increased expression of HMG-I protein leads to
      the neoplastic transformation of both Rat 1a fibroblasts and CB33 cells. In
      addition, Rat 1a cells overexpressing HMG-I protein form tumors in nude mice.
      Decreasing HMG-I/Y proteins using an antisense construct abrogates transformation
      in Burkitt's lymphoma cells. These findings indicate that HMG-I/Y is a c-Myc
      target gene involved in neoplastic transformation and a member of a new class of
      potential oncogenes.

PMID- 10891490
TI  - CD40 induces apoptosis in carcinoma cells through activation of cytotoxic ligands
      of the tumor necrosis factor superfamily.
AB  - CD40, a tumor necrosis factor (TNF) receptor (TNFR) family member, conveys
      signals regulating diverse cellular responses, ranging from proliferation and
      differentiation to growth suppression and cell death. The ability of CD40 to
      mediate apoptosis in carcinoma cells is intriguing given the fact that the CD40
      cytoplasmic C terminus lacks a death domain homology with the cytotoxic members
      of the TNFR superfamily, such as Fas, TNFR1, and TNF-related apoptosis-inducing
      ligand (TRAIL) receptors. In this study, we have probed the mechanism by which
      CD40 transduces death signals. Using a trimeric recombinant soluble CD40 ligand
      to activate CD40, we have found that this phenomenon critically depends on the
      membrane proximal domain (amino acids 216 to 239) but not the TNFR-associated
      factor-interacting PXQXT motif in the CD40 cytoplasmic tail. CD40-mediated
      cytotoxicity is blocked by caspase inhibitors, such as zVAD-fmk and crmA, and
      involves activation of caspase 8 and caspase 3. Interestingly, CD40 ligation was
      found to induce functional Fas ligand, TRAIL (Apo-2L) and TNF in apoptosis
      susceptible carcinoma cells and to up-regulate expression of Fas. These findings
      identify a novel proapoptotic mechanism which is induced by CD40 in carcinoma
      cells and depends on the endogenous production of cytotoxic cytokines and
      autocrine or paracrine induction of cell death.

PMID- 10891491
TI  - Bop1 is a mouse WD40 repeat nucleolar protein involved in 28S and 5. 8S RRNA
      processing and 60S ribosome biogenesis.
AB  - We have identified and characterized a novel mouse protein, Bop1, which contains
      WD40 repeats and is highly conserved through evolution. bop1 is ubiquitously
      expressed in all mouse tissues examined and is upregulated during mid-G(1) in
      serum-stimulated fibroblasts. Immunofluorescence analysis shows that Bop1 is
      localized predominantly to the nucleolus. In sucrose density gradients, Bop1 from
      nuclear extracts cosediments with the 50S-80S ribonucleoprotein particles that
      contain the 32S rRNA precursor. RNase A treatment disrupts these particles and
      releases Bop1 into a low-molecular-weight fraction. A mutant form of Bop1,
      Bop1Delta, which lacks 231 amino acids in the N- terminus, is colocalized with
      wild-type Bop1 in the nucleolus and in ribonucleoprotein complexes. Expression of
      Bop1Delta leads to cell growth arrest in the G(1) phase and results in a specific
      inhibition of the synthesis of the 28S and 5.8S rRNAs without affecting 18S rRNA
      formation. Pulse-chase analyses show that Bop1Delta expression results in a
      partial inhibition in the conversion of the 36S to the 32S pre-rRNA and a
      complete inhibition of the processing of the 32S pre-rRNA to form the mature 28S
      and 5.8S rRNAs. Concomitant with these defects in rRNA processing, expression of
      Bop1Delta in mouse cells leads to a deficit in the cytosolic 60S ribosomal
      subunits. These studies thus identify Bop1 as a novel, nonribosomal mammalian
      protein that plays a key role in the formation of the mature 28S and 5.8S rRNAs
      and in the biogenesis of the 60S ribosomal subunit.

PMID- 10891492
TI  - Identification of B-KSR1, a novel brain-specific isoform of KSR1 that functions
      in neuronal signaling.
AB  - Kinase suppressor of Ras (KSR) is an evolutionarily conserved component of Ras
      dependent signaling pathways. Here, we report the identification of B-KSR1, a
      novel splice variant of murine KSR1 that is highly expressed in brain-derived
      tissues. B-KSR1 protein is detectable in mouse brain throughout embryogenesis, is
      most abundant in adult forebrain neurons, and is complexed with activated mitogen
      activated protein kinase (MAPK) and MEK in brain tissues. Expression of B-KSR1 in
      PC12 cells resulted in accelerated nerve growth factor (NGF)-induced neuronal
      differentiation and detectable epidermal growth factor (EGF)-induced neurite
      outgrowth. Sustained MAPK activity was observed in cells stimulated with either
      NGF or EGF, and all effects on neurite outgrowth could be blocked by the MEK
      inhibitor PD98059. In B-KSR1-expressing cells, the MAPK-B-KSR1 interaction was
      inducible and correlated with MAPK activation, while the MEK-B-KSR1 interaction
      was constitutive. Further examination of the MEK-B-KSR1 interaction revealed that
      all genetically identified loss-of-function mutations in the catalytic domain
      severely diminished MEK binding. Moreover, B-KSR1 mutants defective in MEK
      binding were unable to augment neurite outgrowth. Together, these findings
      demonstrate the functional importance of MEK binding and indicate that B-KSR1 may
      function to transduce Ras-dependent signals that are required for neuronal
      differentiation or that are involved in the normal functioning of the mature
      central nervous system.

PMID- 10891493
TI  - Adenovirus E1B 55-kilodalton oncoprotein inhibits p53 acetylation by PCAF.
AB  - The adenovirus E1B 55-kDa protein binds to cellular tumor suppressor p53 and
      inactivates its transcriptional transactivation function. p53 transactivation
      activity is dependent upon its ability to bind to specific DNA sequences near the
      promoters of its target genes. It was shown recently that p53 is acetylated by
      transcriptional coactivators p300, CREB bidning protein (CBP), and PCAF and that
      acetylation of p53 by these proteins enhances p53 sequence-specific DNA binding.
      Here we show that the E1B 55-kDa protein specifically inhibits p53 acetylation by
      PCAF in vivo and in vitro, while acetylation of histones and PCAF autoacetylation
      is not affected. Furthermore, the DNA-binding activity of p53 is diminished in
      cells expressing the E1B 55-kDa protein. PCAF binds to the E1B 55-kDa protein and
      to a region near the C terminus of p53 encompassing Lys-320, the specific PCAF
      acetylation site. We further show that the E1B 55-kDa protein interferes with the
      physical interaction between PCAF and p53, suggesting that the E1B 55-kDa protein
      inhibits PCAF acetylase function on p53 by preventing enzyme-substrate
      interaction. These results underscore the importance of p53 acetylation for its
      function and suggest that inhibition of p53 acetylation by viral oncoproteins
      prevent its activation, thereby contributing to viral transformation.

PMID- 10891494
TI  - Defect in the p53-Mdm2 autoregulatory loop resulting from inactivation of
      TAF(II)250 in cell cycle mutant tsBN462 cells.
AB  - The cell cycle arrest and proapoptotic functions of p53 are under tight control
      by Mdm2. After stress activation of p53 by nontranscriptional mechanisms,
      transcription of the mdm2 gene results in increased synthesis of Mdm2 and down
      regulation of p53. Disruption of this autoregulatory loop has profound effects on
      cell survival and tumorigenesis. We show that a defective p53-Mdm2 autoregulatory
      loop results from inactivation of a basal transcription factor, TAF(II)250, in
      tsBN462 cells. We found that Mdm2 expression rescues the temperature-sensitive
      phenotype of tsBN462 cells, as shown by activation of cell cycle-regulated gene
      promoters (B-myb, cyclin A, and cdc25C), increased cell growth and DNA synthesis,
      and inhibition of apoptosis. These effects of Mdm2 are mediated by p53. Exogenous
      Mdm2 expression apparently complements endogenous Mdm2 synthesis in tsBN462
      cells, which is reduced compared to that in the equivalent parental cells with
      wild-type TAF(II)250, BHK21. Expression of wild-type TAF(II)250 in tsBN462
      stimulates and prolongs the synthesis of Mdm2 and rescues the temperature
      sensitive phenotype. The TAF(II)250 rescue is blocked by inhibition of Mdm2-p53
      interactions. We also show that Mdm2 promoter activation, after transfer to the
      nonpermissive temperature, is attenuated in cells with mutant TAF(II)250. The
      temperature-sensitive phenotype apparently results from inefficient inhibition of
      heat-induced p53 by reduced Mdm2 synthesis due to low mdm2 promoter activity.
      These results raise the possibility that the p53-Mdm2 autoregulatory loop could
      guard against transcriptional defects in cells.

PMID- 10891495
TI  - Establishment of irreversible growth arrest in myogenic differentiation requires
      the RB LXCXE-binding function.
AB  - The crystal structure of the A-B domain of RB has defined the binding pocket for
      the LXCXE peptide motif. Using the crystal structure as a guide, we have
      inactivated the LXCXE-binding pocket by replacing N757 with Phe [to obtain
      RB(N757F)]. RB(N757F) does not bind to viral oncoproteins but retains the ability
      to bind and inhibit E2F. RB(N757F) is less effective than the wild-type RB
      [RB(WT)] in repressing E2F-regulated transcription, and its repression activity
      is not affected by trichostatin A, an inhibitor of histone deacetylases. However,
      RB(N757F) is as effective as RB(WT) in suppressing cell growth. Interestingly,
      RB(N757F) cannot establish an irreversible growth arrest in differentiated
      myocytes. Differentiated myocytes with RB(WT) become refractory to serum. By
      contrast, differentiated myocytes with RB(N757F) undergo DNA synthesis and
      phosphorylate RB(N757F) in response to serum, despite a high level of p21Cip1
      expression. Mutation of the phosphorylation sites in RB(N757F) rescued its defect
      and allowed myocytes to permanently withdraw from the cell cycle. These results
      demonstrate that it is possible to inactivate the LXCXE-binding pocket without
      compromising the overall integrity of RB. Moreover, the LXCXE-binding pocket is
      dispensable for the intrinsic growth suppression function of RB. However, the
      LXCXE-binding function is essential for RB to establish the serum-refractory
      state in differentiated myocytes.

PMID- 10891496
TI  - Long-distance control of origin choice and replication timing in the human beta
      globin locus are independent of the locus control region.
AB  - DNA replication in the human beta-globin locus is subject to long-distance
      regulation. In murine and human erythroid cells, the human locus replicates in
      early S phase from a bidirectional origin located near the beta-globin gene. This
      Hispanic thalassemia deletion removes regulatory sequences located over 52 kb
      from the origin, resulting in replication of the locus from a different origin, a
      shift in replication timing to late S phase, adoption of a closed chromatin
      conformation, and silencing of globin gene expression in murine erythroid cells.
      The sequences deleted include nuclease-hypersensitive sites 2 to 5 (5'HS2-5) of
      the locus control region (LCR) plus an additional 27-kb upstream region. We
      tested a targeted deletion of 5'HS2-5 in the normal chromosomal context of the
      human beta-globin locus to determine the role of these elements in replication
      origin choice and replication timing. We demonstrate that the 5'HS2-5-deleted
      locus initiates replication at the appropriate origin and with normal timing in
      murine erythroid cells, and therefore we conclude that 5'HS2-5 in the classically
      defined LCR do not control replication in the human beta-globin locus. Recent
      studies also show that targeted deletion of 5'HS2-5 results in a locus that lacks
      globin gene expression yet retains an open chromatin conformation. Thus, the
      replication timing of the locus is closely correlated with nuclease sensitivity
      but not globin gene expression.

PMID- 10891497
TI  - A novel murine Staufen isoform modulates the RNA content of Staufen complexes.
AB  - Mouse Staufen (mStau) is a double-stranded RNA-binding protein associated with
      polysomes and the rough endoplasmic reticulum (RER). We describe a novel
      endogenous isoform of mStau (termed mStau(i)) which has an insertion of six amino
      acids within dsRBD3, the major double-stranded RNA (dsRNA)-binding domain. With a
      structural change of the RNA-binding domain, this conserved and widely
      distributed isoform showed strongly impaired dsRNA-binding ability. In
      transfected cells, mStau(i) exhibited the same tubulovesicular distribution (RER)
      as mStau when weakly expressed; however, when overexpressed, mStau(i) was found
      in large cytoplasmic granules. Markers of the RER colocalized with mStau(i)
      containing granules, showing that overexpressed mStau(i) could still be
      associated with the RER. Cotransfection of mStau(i) with mStau relocalized
      overexpressed mStau(i) to the reticular RER, suggesting that they can form a
      complex on the RER and that a balance between these isoforms is important to
      achieve proper localization. Coimmunoprecipitation demonstrated that the two
      mStau isoforms are components of the same complex in vivo. Analysis of the
      immunoprecipitates showed that mStau is a component of an RNA-protein complex and
      that the association with mStau(i) drastically reduces the RNA content of the
      complex. We propose that this new isoform, by forming a multiple-isoform complex,
      regulates the amount of RNA in mStau complexes in mammalian cells.

PMID- 10891498
TI  - MCG10, a novel p53 target gene that encodes a KH domain RNA-binding protein, is
      capable of inducing apoptosis and cell cycle arrest in G(2)-M.
AB  - p53, a tumor suppressor, inhibits cell proliferation by inducing cellular genes
      involved in the regulation of the cell cycle. MCG10, a novel cellular p53 target
      gene, was identified in a cDNA subtraction assay with mRNA isolated from a p53
      producing cell line. MCG10 can be induced by wild-type but not mutant p53 and by
      DNA damage via two potential p53-responsive elements in the promoter of the MCG10
      gene. The MCG10 gene contains 10 exons and is located at chromosome 3p21, a
      region highly susceptible to aberrant chromosomal rearrangements and deletions in
      human neoplasia. The MCG10 gene locus encodes at least two alternatively spliced
      transcripts, MCG10 and MCG10as. The MCG10 and MCG10as proteins contain two
      domains homologous to the heterogeneous nuclear ribonucleoprotein K homology (KH)
      domain. By generating cell lines that inducibly express either wild-type or
      mutated forms of MCG10 and MCG10as, we found that MCG10 and MCG10as can suppress
      cell proliferation by inducing apoptosis and cell cycle arrest in G(2)-M. In
      addition, we found that MCG10 and MCG10as, through their KH domains, can bind
      poly(C) and that their RNA-binding activity is necessary for inducing apoptosis
      and cell cycle arrest. Furthermore, we found that the level of the poly(C)
      binding MCG10 protein is increased in cells treated with the DNA-damaging agent
      camptothecin in a p53-dependent manner. These results suggest that the MCG10 RNA
      binding protein is a potential mediator of p53 tumor suppression.

PMID- 10891499
TI  - Nup50, a nucleoplasmically oriented nucleoporin with a role in nuclear protein
      export.
AB  - We present here a detailed analysis of a rat polypeptide termed Nup50 (formerly
      NPAP60) that was previously found to be associated with the nuclear pore complex
      (F. Fan et al., Genomics 40:444-453, 1997). We have found that Nup50 (and/or a
      related 70-kDa polypeptide) is present in numerous rat cells and tissues. By
      immunofluorescence microscopy, Nup50 was found to be highly concentrated at the
      nuclear envelope of rat liver nuclei, whereas in cultured NRK cells it also is
      abundant in intranuclear regions. On the basis of immunogold electron microscopy
      of both rat liver nuclear envelopes and NRK cells, we determined that Nup50 is
      specifically localized in the nucleoplasmic fibrils of the pore complex.
      Microinjection of anti-Nup50 antibodies into the nucleus of NRK cells resulted in
      strong inhibition of nuclear export of a protein containing a leucine-rich
      nuclear export sequence, whereas nuclear import of a protein containing a
      classical nuclear localization sequence was unaffected. Correspondingly, CRM1,
      the export receptor for leucine-rich export sequences, directly bound to a
      fragment of Nup50 in vitro, whereas several other import and export receptors did
      not significantly interact with this fragment. Taken together, our data indicate
      that Nup50 has a direct role in nuclear protein export and probably serves as a
      binding site on the nuclear side of the pore complex for export receptor-cargo
      complexes.

PMID- 10891500
TI  - Characterization and targeted disruption of murine Nup50, a p27(Kip1)-interacting
      component of the nuclear pore complex.
AB  - p27(Kip1) is a member of the Cip-Kip family of cyclin-dependent kinase (Cdk)
      inhibitors that binds to cyclin-Cdk complexes and inhibits their catalytic
      activity in response to antiproliferative stimuli. p27(Kip1) is regulated by
      several posttranscriptional mechanisms, including subcellular localization. We
      have identified a component of the nuclear pore complex (NPC), termed Nup50,
      through its two-hybrid interactions with p27(Kip1). Nup50 is a nucleoplasmically
      oriented component of the nuclear pore complex with a role in protein export (T.
      Guan, R. H. Kehlenbach, E. C. Schirmer, A. Kehlenbach, F. Fan, B. E. Clurman, N.
      Arnheim, and L. Gerace, Mol. Cell. Biol. 20:5619-5630, 2000). We found that
      murine Nup50 is a widely expressed nucleoporin and that Nup50 expression is
      highest in the developing neural tube and adult testes. We have also examined
      interactions between Nup50 and the NPC and found specific two-hybrid interactions
      between Nup50 and several well-defined components of the NPC, as well as
      coimmunoprecipitation of Nup50 with the nucleoporin Nup153 from transfected
      mammalian cells. In order to study Nup50 function in vivo, we cloned the mouse
      Nup50 genomic locus and created a targeted Nup50 deletion in the mouse germ line.
      Nup50 disruption resulted in a complex phenotype characterized by late embryonic
      lethality, neural tube defects, and intrauterine growth retardation. Although
      Nup50-null mouse embryo fibroblasts exhibited no defects in either cell cycle
      control or p27(Kip1) regulation, Nup50 deletion was associated with abnormalities
      in p27(Kip1) expression and cell proliferation in the developing neuroepithelium.
      We conclude that Nup50 is a nucleoporin with essential functions during mouse
      development.

PMID- 10891501
TI  - Hemorrhage, impaired hematopoiesis, and lethality in mouse embryos carrying a
      targeted disruption of the Fli1 transcription factor.
AB  - The Ets family of transcription factors have been suggested to function as key
      regulators of hematopoeisis. Here we describe aberrant hematopoeisis and
      hemorrhaging in mouse embryos homozygous for a targeted disruption in the Ets
      family member, Fli1. Mutant embryos are found to hemorrhage from the dorsal aorta
      to the lumen of the neural tube and ventricles of the brain (hematorrhachis) on
      embryonic day 11.0 (E11.0) and are dead by E12.5. Histological examinations and
      in situ hybridization reveal disorganization of columnar epithelium and the
      presence of hematomas within the neuroepithelium and disruption of the basement
      membrane lying between this and mesenchymal tissues, both of which express Fli1
      at the time of hemorrhaging. Livers from mutant embryos contain few
      pronormoblasts and basophilic normoblasts and have drastically reduced numbers of
      colony forming cells. These defects occur with complete penetrance of phenotype
      regardless of the genetic background (inbred B6, hybrid 129/B6, or outbred CD1)
      or the targeted embryonic stem cell line used for the generation of knockout
      lines. Taken together, these results provide in vivo evidence for the role of
      Fli1 in the regulation of hematopoiesis and hemostasis.

PMID- 10891502
TI  - Mutations in conserved regions of the predicted RAG2 kelch repeats block
      initiation of V(D)J recombination and result in primary immunodeficiencies.
AB  - The V(D)J recombination reaction is composed of multiple nucleolytic processing
      steps mediated by the recombination-activating proteins RAG1 and RAG2. Sequence
      analysis has suggested that RAG2 contains six kelch repeat motifs that are
      predicted to form a six-bladed beta-propeller structure, with the second beta
      strand of each repeat demonstrating marked conservation both within and between
      kelch repeat-containing proteins. Here we demonstrate that mutations G95R and
      DeltaI273 within the predicted second beta-strand of repeats 2 and 5 of RAG2 lead
      to immunodeficiency in patients P1 and P2. Green fluorescent protein fusions with
      the mutant proteins reveal appropriate localization to the nucleus. However, both
      mutations reduce the capacity of RAG2 to interact with RAG1 and block
      recombination signal cleavage, therefore implicating a defect in the early steps
      of the recombination reaction as the basis of the clinical phenotype. The present
      experiments, performed with an extensive panel of site-directed mutations within
      each of the six kelch motifs, further support the critical role of both
      hydrophobic and glycine-rich regions within the second beta-strand for RAG1-RAG2
      interaction and recombination signal recognition and cleavage. In contrast,
      multiple mutations within the variable-loop regions of the kelch repeats had
      either mild or no effects on RAG1-RAG2 interaction and hence on the ability to
      mediate recombination. In all, the data demonstrate a critical role of the RAG2
      kelch repeats for V(D)J recombination and highlight the importance of the
      conserved elements of the kelch motif.

PMID- 10891503
TI  - Identification of the cytolinker plectin as a major early in vivo substrate for
      caspase 8 during CD95- and tumor necrosis factor receptor-mediated apoptosis.
AB  - Caspase 8 plays an essential role in the execution of death receptor-mediated
      apoptosis. To determine the localization of endogenous caspase 8, we used a panel
      of subunit-specific anti-caspase 8 monoclonal antibodies in confocal
      immunofluorescence microscopy. In the human breast carcinoma cell line MCF7,
      caspase 8 predominantly colocalized with and bound to mitochondria. After
      induction of apoptosis through CD95 or tumor necrosis factor receptor I, active
      caspase 8 translocated to plectin, a major cross-linking protein of the three
      main cytoplasmic filament systems, whereas the caspase 8 prodomain remained bound
      to mitochondria. Plectin was quantitatively cleaved by caspase 8 at Asp 2395 in
      the center of the molecule in all cells tested. Cleavage of plectin clearly
      preceded that of other caspase substrates such as poly(ADP-ribose) polymerase,
      gelsolin, cytokeratins, or lamin B. In primary fibroblasts from plectin-deficient
      mice, apoptosis-induced reorganization of the actin cytoskeleton, as seen in wild
      type cells, was severely impaired, suggesting that during apoptosis, plectin is
      required for the reorganization of the microfilament system.

PMID- 10891504
TI  - Bcl-x(L) prevents the initial decrease in mitochondrial membrane potential and
      subsequent reactive oxygen species production during tumor necrosis factor alpha
      induced apoptosis.
AB  - The Bcl-2 family of proteins are involved in regulating the redox state of cells.
      However, the mode of action of Bcl-2 proteins remains unclear. This work analyzed
      the effects of Bcl-x(L) on the cellular redox state after treatment with tumor
      necrosis factor alpha (TNF-alpha) or exogenous oxidants. We show that in cells
      that undergo TNF-alpha-induced apoptosis, TNF-alpha induces a partial decrease in
      mitochondrial membrane potential (DeltaPsi(m)) followed by high levels of
      reactive oxygen species (ROS). ROS scavengers delay the progression of
      mitochondrial depolarization and apoptotic cell death. This indicates that ROS
      are important mediators of mitochondrial depolarization. However, ROS scavengers
      fail to prevent the initial TNF-alpha-induced decrease in DeltaPsi(m). In
      contrast, expression of Bcl-x(L) prevents both the initial decrease in
      DeltaPsi(m) following TNF-alpha treatment and the subsequent induction of ROS.
      Bcl-x(L) itself does not act as a ROS scavenger. In addition, Bcl-x(L) does not
      block the initial decrease in DeltaPsi(m) following treatment with the oxidant
      hydrogen peroxide. However, unlike control-transfected cells, Bcl-x(L)-expressing
      cells can recover their mitochondrial membrane potential following the initial
      drop in DeltaPsi(m) induced by hydrogen peroxide. These data suggest that Bcl
      x(L) plays a regulatory role in controlling the membrane potential of and ROS
      production by mitochondria rather than acting as a direct antioxidant.

PMID- 10891505
TI  - Evidence for a telomere-independent "clock" limiting RAS oncogene-driven
      proliferation of human thyroid epithelial cells.
AB  - An initiating role for RAS oncogene mutation in several epithelial cancers is
      supported by its high incidence in early-stage tumors and its ability to induce
      proliferation in the corresponding normal cells in vitro. Using retroviral
      transduction of thyroid epithelial cells as a model we ask here: (i) how mutant
      RAS can induce long-term proliferation in an epithelial cell in contrast to the
      premature senescence observed in fibroblasts; and (ii) what is the "clock" which
      eventually triggers spontaneous growth arrest even in epithelial clones generated
      by mutant RAS. The early response to RAS activation in thyroid epithelial cells
      showed two features not seen in fibroblasts: (i) a marked decrease in expression
      of the cyclin-dependent kinase inhibitor (CDKI) p27(kip1) and (ii) the absence of
      any induction of p21(waf1). When proliferation eventually ceased (after up to 20
      population doublings) this occurred despite undiminished expression of mutant RAS
      and was tightly correlated with a return to the initial high level of p27(kip1)
      expression, together with the de novo appearance of p16(ink4a). Importantly,
      neither the CDKI changes nor the proliferative life span of RAS-induced
      epithelial clones was altered by induction of telomerase activity through forced
      expression of the catalytic subunit, hTERT, at levels sufficient to immortalize
      human fibroblasts. These data provide a basis for cell-type differences in
      sensitivity to RAS-induced proliferation which may explain the corresponding
      tumor-type specificity of RAS mutation. They also show for the first time in a
      primary human cell model that a telomere-independent mechanism can limit not only
      physiological but also oncogene-driven proliferation, pointing therefore to a
      tumour suppressor mechanism additional, or alternative, to the telomere clock.

PMID- 10891506
TI  - Histone-histone interactions and centromere function.
AB  - Cse4p is a structural component of the core centromere of Saccharomyces
      cerevisiae and is a member of the conserved CENP-A family of specialized histone
      H3 variants. The histone H4 allele hhf1-20 confers defects in core centromere
      chromatin structure and mitotic chromosome transmission. We have proposed that
      Cse4p and histone H4 interact through their respective histone fold domains to
      assemble a nucleosome-like structure at centromeric DNA. To test this model, we
      targeted random mutations to the Cse4p histone fold domain and isolated three
      temperature-sensitive cse4 alleles in an unbiased genetic screen. Two of the cse4
      alleles contain mutations at the Cse4p-H4 interface. One of these requires two
      widely separated mutations demonstrating long-range cooperative interactions in
      the structure. The third cse4 allele is mutated at its helix 2-helix 3 interface,
      a region required for homotypic H3 fold dimerization. Overexpression of wild-type
      Cse4p and histone H4 confer reciprocal allele-specific suppression of cse4 and
      hhf1 mutations, providing strong evidence for Cse4p-H4 protein interaction.
      Overexpression of histone H3 is dosage lethal in cse4 mutants, suggesting that
      histone H3 competes with Cse4p for histone H4 binding. However, the relative
      resistance of the Cse4p-H4 pathway to H3 interference argues that centromere
      chromatin assembly must be highly regulated.

PMID- 10891507
TI  - Effect of phosphoinositide-dependent kinase 1 on protein kinase B translocation
      and its subsequent activation.
AB  - In this report we investigated the function of phosphoinositide-dependent protein
      kinase 1 (PDK1) in protein kinase B (PKB) activation and translocation to the
      cell surface. Wild-type and PDK1 mutants were transfected into HeLa cells, and
      their subcellular localization was analyzed. PDK1 was found to translocate to the
      plasma membrane in response to insulin, and this process did not require a
      functional catalytic activity, since a catalytically inactive kinase mutant (Kd)
      of PDK1 was capable of translocating. The PDK1 presence at the cell surface was
      shown to be linked to phospholipids and therefore to serum-dependent
      phosphatidylinositol 3-kinase activity. Using confocal microscopy in HeLa cells
      we found that PDK1 colocalizes with PKB at the plasma membrane. Further, after
      cotransfection of PKB and a PDK1 mutant (Mut) unable to translocate to the plasma
      membrane, PKB was prevented from moving to the cell periphery after insulin
      stimulation. In response to insulin, a PKB mutant with its PH domain deleted
      (DeltaPH-PKB) retained the ability to translocate to the plasma membrane when
      coexpressed with PDK1. Finally, we found that DeltaPH-PKB was highly active
      independent of insulin stimulation when cotransfected with PDK1 mutants defective
      in their PH domain. These findings suggest that PDK1 brings PKB to the plasma
      membrane upon exposure of cells to insulin and that the PH domain of PDK1 acts as
      a negative regulator of its enzyme activity.

PMID- 10891508
TI  - Modulation of histone acetyltransferase activity through interaction of epstein
      barr nuclear antigen 3C with prothymosin alpha.
AB  - The Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is essential for EBV
      dependent immortalization of human primary B lymphocytes. Genetic analysis
      indicated that amino acids 365 to 992 are important for EBV-mediated
      immortalization of B lymphocytes. We demonstrate that this region of EBNA3C
      critical for immortalization interacts with prothymosin alpha (ProTalpha), a
      cellular protein previously identified to be important for cell division and
      proliferation. This interaction maps to a region downstream of amino acid 365
      known to be involved in transcription regulation and critical for EBV-mediated
      transformation of primary B lymphocytes. Additionally, we show that EBNA3C also
      interacts with p300, a cellular acetyltransferase. This interaction suggests a
      possible role in regulation of histone acetylation and chromatin remodeling. An
      increase in histone acetylation was observed in EBV-transformed lymphoblastoid
      cell lines, which is consistent with increased cellular gene expression. These
      cells express the entire repertoire of latent nuclear antigens, including EBNA3C.
      Expression of EBNA3C in cells with increased acetyltransferase activity mediated
      by the EBV transactivator EBNA2 results in down-modulation of this activity in a
      dose-responsive manner. The interactions of EBNA3C with ProTalpha and p300
      provide new evidence implicating this essential EBV protein EBNA3C in modulating
      the acetylation of cellular factors, including histones. Hence, EBNA3C plays a
      critical role in balancing cellular transcriptional events by linking the
      biological property of mediating inhibition of EBNA2 transcription activation and
      the observed histone acetyltransferase activity, thereby orchestrating
      immortalization of EBV-infected cells.

PMID- 10891509
TI  - Assembly and preferential localization of Nup116p on the cytoplasmic face of the
      nuclear pore complex by interaction with Nup82p.
AB  - The yeast Saccharomyces cerevisiae nucleoporin Nup116p serves as a docking site
      for both nuclear import and export factors. However, the mechanism for assembling
      Nup116p into the nuclear pore complex (NPC) has not been resolved. By conducting
      a two-hybrid screen with the carboxy (C)-terminal Nup116p region as bait, we
      identified Nup82p. The predicted coiled-coil region of Nup82p was not required
      for Nup116p interaction, making the binding requirements distinct from those for
      the Nsp1p-Nup82p-Nup159p subcomplex (N. Belgareh, C. Snay-Hodge, F. Pasteau, S.
      Dagher, C. N. Cole, and V. Doye, Mol. Biol. Cell 9:3475-3492, 1998).
      Immunoprecipitation experiments using yeast cell lysates resulted in the
      coisolation of a Nup116p-Nup82p subcomplex. Although the absence of Nup116p had
      no effect on the NPC localization of Nup82p, overexpression of C-terminal Nup116p
      in a nup116 null mutant resulted in Nup82p mislocalization. Moreover, NPC
      localization of Nup116p was specifically diminished in a nup82-Delta108 mutant
      after growth at 37 degrees C. Immunoelectron microscopy analysis showed Nup116p
      was localized on both the cytoplasmic and nuclear NPC faces. Its distribution was
      asymmetric with the majority at the cytoplasmic face. Taken together, these
      results suggest that Nup82p and Nup116p interact at the cytoplasmic NPC face,
      with nucleoplasmic Nup116p localization utilizing novel binding partners.

PMID- 10891510
TI  - Species-specific elements in the large T-antigen J domain are required for
      cellular transformation and DNA replication by simian virus 40.
AB  - The J domain of simian virus 40 (SV40) large T antigen is required for efficient
      DNA replication and transformation. Despite previous reports demonstrating the
      promiscuity of J domains in heterologous systems, results presented here show the
      requirement for specific J-domain sequences in SV40 large-T-antigen-mediated
      activities. In particular, chimeric-T-antigen constructs in which the SV40 T
      antigen J domain was replaced with that from the yeast Ydj1p or Escherichia coli
      DnaJ proteins failed to replicate in BSC40 cells and did not transform REF52
      cells. However, T antigen containing the JC virus J domain was functional in
      these assays, although it was less efficient than the wild type. The inability of
      some large-T-antigen chimeras to promote DNA replication and elicit cellular
      transformation was not due to a failure to interact with hsc70, since a
      nonfunctional chimera, containing the DnaJ J domain, bound hsc70. However, this
      nonfunctional chimeric T antigen was reduced in its ability to stimulate hsc70
      ATPase activity and unable to liberate E2F from p130, indicating that
      transcriptional activation of factors required for cell growth and DNA
      replication may be compromised. Our data suggest that the T-antigen J domain
      harbors species-specific elements required for viral activities in vivo.

PMID- 10891511
TI  - The cytoplasmic tyrosines of integrin subunit beta1 are involved in focal
      adhesion kinase activation.
AB  - We have previously shown that mutation of the two tyrosines in the cytoplasmic
      domain of integrin subunit beta1 (Y783 and Y795) to phenylalanines markedly
      reduces the capability of beta1A integrins to mediate directed cell migration. In
      this study, beta1-dependent cell spreading was found to be delayed in GD25 cells
      expressing beta1A(Y783/795F) compared to that in wild-type GD25-beta1A. Focal
      adhesion kinase (FAK) tyrosine phosphorylation and activation were severely
      impaired in response to beta1-dependent adhesion in GD25-beta1A(Y783/795F) cells
      compared to that in wild-type GD25-beta1A or mutants in which only a single
      tyrosine was altered (beta1A(Y783F) or beta1A(Y795F)). Phosphorylation site
      specific antibodies selective for FAK phosphotyrosine 397 indicated that the
      defect in FAK phosphorylation via beta1A(Y783/795F) lies at the level of the
      initial autophosphorylation step. Indeed, beta1A-dependent tyrosine
      phosphorylation of tensin and paxillin was lost in the beta1A(Y783/795F) cells,
      consistent with the impairment in FAK activation. In contrast, p130(CAS) overall
      tyrosine phosphorylation was unaffected by the beta1 mutations. Despite the
      defect in beta1-mediated FAK activation, FAK was still localized to focal
      adhesions. Taken together, the phenotype of the GD25-beta1A(Y783/795F) cells
      resembles, but is distinct from, the phenotype observed in FAK-null cells. These
      observations argue that tyrosines 783 and 795 within the cytoplasmic tail of
      integrin subunit beta1A are critical mediators of FAK activation and cell
      spreading in GD25 cells.

PMID- 10891512
TI  - Activation of the Kss1 invasive-filamentous growth pathway induces Ty1
      transcription and retrotransposition in Saccharomyces cerevisiae.
AB  - Using a set of genomic TY1A-lacZ fusions, we show that Ste12 and Tec1, two
      transcription factors of the Kss1 mitogen-activated protein kinase (MAPK) cascade
      activate Ty1 transcription in Saccharomyces cerevisiae. This result strongly
      suggests that the invasive-filamentous pathway regulates Ty1 transcription. Since
      this pathway is active in diploid cells, we suspected that Ty1 transposition
      might occur in this cell type, despite the fact that this event has been never
      reported before (unless activated by heterologous promoters such as that of
      GAL1). We demonstrate here that constitutive activation of the invasive
      filamentous pathway by the STE11-4 allele or by growth in low-nitrogen medium
      induces Ty1 transcription and retrotransposition in diploid cells. We show that
      Ty1 retrotransposition can be activated by STE11-4 in haploid cells as well. Our
      findings provide the first evidence that Ty1 retrotransposition can be activated
      by environmental signals that affect differentiation. Activation of the Kss1 MAPK
      cascade by stress is known to cause filament formation that permits the search
      for nutrients away from the colonization site. We propose that activation of Ty1
      retrotransposition by this cascade could play a role in adaptive mutagenesis in
      response to stress.

PMID- 10891513
TI  - Architecture of the replication fork stalled at the 3' end of yeast ribosomal
      genes.
AB  - Every unit of the rRNA gene cluster of Saccharomyces cerevisiae contains a unique
      site, termed the replication fork barrier (RFB), where progressing replication
      forks are stalled in a polar manner. In this work, we determined the positions of
      the nascent strands at the RFB at nucleotide resolution. Within an HpaI-HindIII
      fragment essential for the RFB, a major and two closely spaced minor arrest sites
      were found. In the majority of molecules, the stalled lagging strand was
      completely processed and the discontinuously synthesized nascent lagging strand
      was extended three bases farther than the continuously synthesized leading
      strand. A model explaining these findings is presented. Our analysis included for
      the first time the use of T4 endonuclease VII, an enzyme recognizing branched DNA
      molecules. This enzyme cleaved predominantly in the newly synthesized homologous
      arms, thereby specifically releasing the leading arm.

PMID- 10891514
TI  - Environmental and heritable factors in the causation of cancer--analyses of
      cohorts of twins from Sweden, Denmark, and Finland.
AB  - BACKGROUND: The contribution of hereditary factors to the causation of sporadic
      cancer is unclear. Studies of twins make it possible to estimate the overall
      contribution of inherited genes to the development of malignant diseases.
      METHODS: We combined data on 44,788 pairs of twins listed in the Swedish, Danish,
      and Finnish twin registries in order to assess the risks of cancer at 28
      anatomical sites for the twins of persons with cancer. Statistical modeling was
      used to estimate the relative importance of heritable and environmental factors
      in causing cancer at 11 of those sites. RESULTS: At least one cancer occurred in
      10,803 persons among 9512 pairs of twins. An increased risk was found among the
      twins of affected persons for stomach, colorectal, lung, breast, and prostate
      cancer. Statistically significant effects of heritable factors were observed for
      prostate cancer (42 percent; 95 percent confidence interval, 29 to 50 percent),
      colorectal cancer (35 percent; 95 percent confidence interval, 10 to 48 percent),
      and breast cancer (27 percent; 95 percent confidence interval, 4 to 41 percent).
      CONCLUSIONS: Inherited genetic factors make a minor contribution to
      susceptibility to most types of neoplasms. This finding indicates that the
      environment has the principal role in causing sporadic cancer. The relatively
      large effect of heritability in cancer at a few sites suggests major gaps in our
      knowledge of the genetics of cancer.

PMID- 10891515
TI  - Reconstruction of damaged corneas by transplantation of autologous limbal
      epithelial cells.
AB  - BACKGROUND: Stevens-Johnson syndrome, ocular pemphigoid, and thermal or chemical
      burns can cause scarring and opacification of the cornea and loss of vision.
      Transplantation of epithelial cells from the limbus of the contralateral cornea
      can restore useful vision. However, this procedure requires a large limbal graft
      from the healthy eye and is not possible in patients who have bilateral lesions.
      METHODS: We took specimens of limbal epithelial cells from the healthy
      contralateral eyes of six patients with severe unilateral corneal disease. The
      epithelial cells were cultured and expanded on amniotic membrane. The amniotic
      membrane, together with the sheet of limbal epithelial cells, was transplanted to
      the denuded corneal surface of the damaged eye after superficial keratectomy to
      remove fibrovascular ingrowth. The mean (+/-SD) follow-up period was 15+/-2
      months. RESULTS: Complete reepithelialization of the corneal surface occurred
      within two to four days of transplantation in all six eyes receiving transplants.
      By one month, the ocular surface was covered with corneal epithelium, and the
      clarity of the cornea was improved. In five of the six eyes receiving transplants
      (83 percent), the mean visual acuity improved from 20/112 to 20/45. In one
      patient with a chemical burn who had total opacification of the cornea, the
      acuity improved from the ability to count fingers at 40 cm to 20/200. No patient
      had recurrent neovascularization or inflammation in the transplanted area during
      the follow-up period. CONCLUSIONS: Transplantation of autologous limbal
      epithelial cells cultured on amniotic membrane is a simple and effective method
      of reconstructing the corneal surface and restoring useful vision in patients
      with unilateral deficiency of limbal epithelial cells.

PMID- 10891516
TI  - Validity of a set of clinical criteria to rule out injury to the cervical spine
      in patients with blunt trauma. National Emergency X-Radiography Utilization Study
      Group.
AB  - BACKGROUND: Because clinicians fear missing occult cervical-spine injuries, they
      obtain cervical radiographs for nearly all patients who present with blunt
      trauma. Previous research suggests that a set of clinical criteria (decision
      instrument) can identify patients who have an extremely low probability of injury
      and who consequently have no need for imaging studies. METHODS: We conducted a
      prospective, observational study of such a decision instrument at 21 centers
      across the United States. The decision instrument required patients to meet five
      criteria in order to be classified as having a low probability of injury: no
      midline cervical tenderness, no focal neurologic deficit, normal alertness, no
      intoxication, and no painful, distracting injury. We examined the performance of
      the decision rule in 34,069 patients who underwent radiography of the cervical
      spine after blunt trauma. RESULTS: The decision instrument identified all but 8
      of the 818 patients who had cervical-spine injury (sensitivity, 99.0 percent [95
      percent confidence interval, 98.0 to 99.6 percent]). The negative predictive
      value was 99.8 percent (95 percent confidence interval, 99.6 to 100 percent), the
      specificity was 12.9 percent, and the positive predictive value was 2.7 percent.
      Only two of the patients classified as unlikely to have an injury according to
      the decision instrument met the preset definition of a clinically significant
      injury (sensitivity, 99.6 percent [95 percent confidence interval, 98.6 to 100
      percent]; negative predictive value, 99.9 percent [95 percent confidence
      interval, 99.8 to 100 percent]; specificity, 12.9 percent; positive predictive
      value, 1.9 percent), and only one of these two patients received surgical
      treatment. According to the results of assessment with the decision instrument,
      radiographic imaging could have been avoided in the cases of 4309 (12.6 percent)
      of the 34,069 evaluated patients. CONCLUSIONS: A simple decision instrument based
      on clinical criteria can help physicians to identify reliably the patients who
      need radiography of the cervical spine after blunt trauma. Application of this
      instrument could reduce the use of imaging in such patients.

PMID- 10891517
TI  - Indications for computed tomography in patients with minor head injury.
AB  - BACKGROUND: Computed tomography (CT) is widely used as a screening test in
      patients with minor head injury, although the results are often normal. We
      performed a study to develop and validate a set of clinical criteria that could
      be used to identify patients with minor head injury who do not need to undergo
      CT. METHODS: In the first phase of the study, we recorded clinical findings in
      520 consecutive patients with minor head injury who had a normal score on the
      Glasgow Coma Scale and normal findings on a brief neurologic examination; the
      patients then underwent CT. Using recursive partitioning, we derived a set of
      criteria to identify all patients who had abnormalities on CT scanning. In the
      second phase, the sensitivity and specificity of the criteria for predicting a
      positive scan were evaluated in a group of 909 patients. RESULTS: Of the 520
      patients in the first phase, 36 (6.9 percent) had positive scans. All patients
      with positive CT scans had one or more of seven findings: headache, vomiting, an
      age over 60 years, drug or alcohol intoxication, deficits in short-term memory,
      physical evidence of trauma above the clavicles, and seizure. Among the 909
      patients in the second phase, 57 (6.3 percent) had positive scans. In this group
      of patients, the sensitivity of the seven findings combined was 100 percent (95
      percent confidence interval, 95 to 100 percent). All patients with positive CT
      scans had at least one of the findings. CONCLUSIONS: For the evaluation of
      patients with minor head injury, the use of CT can be safely limited to those who
      have certain clinical findings.

PMID- 10891518
TI  - Images in clinical medicine. Constrictive pericarditis.

PMID- 10891519
TI  - Images in clinical medicine. Constrictive pericarditis.

PMID- 10891520
TI  - The immune system. Second of two parts.

PMID- 10891521
TI  - Drug therapy for breast-feeding women.

PMID- 10891522
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 21-2000. A 13-year-old boy with genital edema and abdominal pain.

PMID- 10891523
TI  - Cancer--nature, nurture, or both.

PMID- 10891524
TI  - Bioengineered corneas--the promise and the challenge.

PMID- 10891525
TI  - Who is at low risk after head or neck trauma?

PMID- 10891526
TI  - Will genetics revolutionize medicine?

PMID- 10891527
TI  - Correction: Case Records of the Massachusetts General Hospital (Case 16-2000).

PMID- 10891528
TI  - Experimental animal models of pancreatic cancer (review).
AB  - Pancreatic adenocarcinoma is currently the fifth leading cause of cancer-related
      death in the United States and is largely refractory to conventional therapies.
      The average survival from diagnosis to death is 4-6 months. The major cause of
      death is rapid development of metastasis involving the lymph nodes, liver, lungs,
      or peritoneum. To understand its etiology and eventually to make prevention
      possible and effective, appropriate carcinogenesis models will certainly help
      shed more light on the process of pancreatic carcinogenesis and help us
      understand the effects of environmental and genetic elements on pancreatic cancer
      development. The development of new treatment strategies to control cancer
      metastasis is of immediate urgency. Fulfillment of this difficult task relies on
      our knowledge of the cellular and molecular biology of pancreatic cancer
      metastasis, and the use of relevant animal models will certainly help define each
      aspect of this complicated process.

PMID- 10891529
TI  - Theophylline and cisplatin synergize in down regulation of BCL-2 induction of
      apoptosis in human granulosa cells transformed by a mutated p53 (p53 val135) and
      Ha-ras oncogene.
AB  - Cisplatin is in common use in ovarian cancer therapy, although it is also
      implicated in cytotoxicity in normal tissue. We have examined the effect of
      cisplatin alone and in combination with theophylline, a phoshodiesterase
      inhibitor, on modulation of Bcl-2/Bax expression and induction of apoptosis in
      human granulosa cells transformed by stable transfection with mutant p53 plus Ha
      ras. Theophylline elicited cell death only at relatively high concentrations with
      an EC50 of 200 microg/ml. Cisplatin exerted its lethal effect with an EC50 of 7
      microM. In the presence of 15 or 50 microg/ml of theophylline (in the range used
      against asthma in humans), the EC50 for cisplatin was reduced to 2 microM or 1.2
      microM, respectively. Using fluorescence-activated cell sorting analysis of DNA
      stained cells and the terminal deoxy-nucleotide tranferase-mediated dUTP nick end
      labeling method, we found that even at concentrations of 0. 3 and 1 microM
      cisplatin, theophylline at 15 and 50 microg/ml increased the incidence of
      apoptosis in these cells by 3-5-fold, while theophylline alone induced extremely
      low apoptosis. Neither drug had any measurable effect on Bax protein expression.
      In contrast Bcl-2 protein expression levels were markedly reduced by theophylline
      and cisplatin in a dose-dependent manner. The combination of theophylline and
      cisplatin resulted in a further dramatic reduction in Bcl-2, under-scoring the
      pronounced synergy of these two drugs. These observations suggest that
      suppression of Bcl-2 expression may play an important role in mediating the
      synergistic effect of cisplatin and theophylline on induction of apoptosis in
      ovarian cancer cells.

PMID- 10891530
TI  - Overexpression of MMP-9 correlates with growth of small hepatocellular carcinoma.
AB  - Matrix metalloproteinases (MMP) play an important role in tumor cell invasion and
      metastasis. We examined the expression of MMPs in hepatocellular carcinoma (HCC)
      to determine whether they may help indicate the progression of HCC and patient
      outcome. The expression of MMP-1, -2, -7, -9, and MT1-MMP were determined in 37
      pairs of HCC and adjacent non-tumor tissue specimens by semiquantitative reverse
      transcription polymerase chain reaction (RT-PCR). The tumor to non-tumor (T/N)
      ratios for mRNA expression of each MMP were compared with the clinicopathological
      findings and two-year disease-free survival rates. Immunohistochemical analysis
      for MMP-1 and -9 was performed in 30 specimens. MMP-1 and -9 expression was
      significantly higher in tumor tissue than in non-tumor tissue (p=0.001 and
      0.0078, respectively). By contrast, the expression of MMP-2 and -7 was
      significantly lower in tumor tissue than in non-tumor tissue (p=0. 003 and 0.03,
      respectively). A higher MMP-9 T/N ratio was significantly associated with small
      HCCs (</=2 cm) and higher serum AFP values (>/=20 ng/ml) (p=0.013 and 0.028,
      respectively). Immunohistochemical analysis suggested that well differentiated
      HCC showed stronger immunoreactivity for MMP-9 than moderately differentiated
      HCC. MMP T/N ratio was not significantly associated with the disease-free
      survival rates. Overexpression of MMP-9 mRNA (T/N ratio >/=2) may be associated
      with the progression of small HCC (</=2 cm).

PMID- 10891531
TI  - Frequent loss of copy number on the long arm of chromosome 21 in human esophageal
      squamous cell carcinoma.
AB  - To understand the molecular pathogenesis of human esophageal cancer, we performed
      a comparative genomic hybridization (CGH) analysis using 10 esophageal squamous
      cell carcinomas. Frequent gains of 1q, 3q, 7p, 7q, 8q, 11q, and 20q and losses of
      3p, 4p, 4q, 5q, 9p, 11p, 11q, 13q, 18q, 21q, and Y were observed. Among these
      regions, 21q has not yet been investigated in detail. We performed an allelotype
      study using 55 squamous cell carcinomas of the esophagus and 20 microsatellite
      markers on 21q and found LOH in 36 cases (65%): 22 (61%) of 36 cases with LOH
      indicated allelic loss in all informative loci, suggesting loss of the whole
      chromosome arm 21q, and five smallest regions of overlap were found. Our present
      results suggest the existence of a tumor suppressor gene(s) that plays a role in
      the genesis of squamous cell carcinoma of the esophagus.

PMID- 10891532
TI  - Contribution of angiogenesis to the progression of colon cancer: possible
      inhibitory effect of angiogenesis inhibitor TNP-470 on tumor growth and hepatic
      metastasis.
AB  - The contribution of angiogenesis to tumor growth and hepatic metastasis of
      colorectal cancer was investigated by means of immunohistochemical study and in
      vitro and in vivo experiments. Colorectal cancer specimens from 30 patients with
      hepatic metastasis and 39 patients without hepatic metastasis were studied by
      staining with antibodies against factor VIII-related antigen. Microvessel count
      in patients with liver metastasis was significantly higher than in those without
      liver metastasis (p<0.005). The effect of TNP-470 was evaluated with in vitro and
      in vivo experiments using human colon cancer cell line, LM and the highly hepatic
      metastasis cell line, LM-H5. The effect of TNP-470 on the proliferation of the
      cancer cells and human umbilical vein endothelial cells (HUVECs) was examined.
      TNP-470 inhibited more sensitively the proliferation of HUVECs than cancer cells
      in vitro. IC50 was approximately 3 pg/ml in HUVECs and approximately 2 microg/ml
      in cancer cells. The effect of TNP-470 on the growth of xenografts and liver
      metastases by LM-H5 in nude mice was examined. TNP-470 (30 mg/kg) was
      administered by subcutaneous injection every third day for 4 weeks. TNP-470
      inhibited both the growth of xenograft and the hepatic metastasis. The number of
      metastatic foci in the liver was 78.2+/-30.1 in the control group and 20.6+/-16.5
      in the treated group. These results suggest that TNP-470 is a potent agent to
      inhibit tumor growth and hepatic metastasis of colon cancer.

PMID- 10891533
TI  - Autocrine motility factor receptor expression associates with tumor progression
      in thymoma.
AB  - We assessed the autocrine motility factor receptor (AMFR/gp78) expression in
      thymoma. AMFR/gp78 antigen was identified in tumor cells in 16 out of 51 (31.4%)
      thymomas. The AMFR/gp78 expression was closely associated with the stage (I/II
      vs. III/IV, p<0.0001), pathological subtypes (epithelial vs. other types,
      p=0.0214), and enhanced expression of alpha-smooth-muscle actin within stroma
      (p<0. 0001). The outcome of the patients with AMFR/gp78 expression was
      significantly worse than for those without it (p<0.01). All initial tumors with
      recurrence expressed AMFR/gp78. The AMFR/gp78 appears to be involved in tumor
      progression in thymoma.

PMID- 10891534
TI  - Expression analysis and mutational screening of the epithelium-specific ets gene
      1 (ESE-1) in patients with squamous anal cancer.
AB  - To investigate whether ESE-1 gene abnormalities are involved in alterations of
      epithelial cell differentiation in squamous anal cancer ESE-1 expression and
      structure were screened in six patients by reverse transcriptase-polymerase chain
      reaction (RT-PCR) and automated sequence analysis. The complete cDNA of isoform
      ESE-1b was always expressed and correctly spliced, with single nucleotide
      polymorphism being observed in two cases. Presence of ESE-1b point mutations was
      excluded. Expression of SPRR2A and ENDOA/CK8, two epithelium-specific ESE-1
      target genes, were revealed by RT-PCR in all cases. This first report of
      expression of ESE-1, and of SPRR2A and ENDOA/CK8 (both related to terminal
      differentiation in different types of epithelia lining) in anal cancer excludes
      the hypothesis that these genes influenced carcinogenesis in our patients.
      Despite selecting of patients without clinical evidence of HPV infection, PCR
      consistently revealed HPV-16 DNA, highlighting the importance of HPV infection in
      anal cancer.

PMID- 10891535
TI  - Differential expression of galectin-1 and galectin-3 in benign and malignant
      salivary gland neoplasms.
AB  - Galectins are a family of non-integrin beta-galactosidase-binding lectins.
      Altered expression of galectins has been associated with neoplastic
      transformation and progression in several human tumors. In this study, we
      examined the distribution patterns of galectin-1 and galectin-3 in normal (n=45),
      benign (n=16), and malignant (n=49) salivary gland specimens using
      immunohistochemistry to determine their diagnostic and/or biological implications
      in salivary gland tumorigenesis. In normal salivary glands, galectin-3 expression
      was limited to ductal cells, and galectin-1 was usually faintly detected in
      ductal cells and strongly positive in myoepithelial cells. In benign tumors,
      galectin-3 maintained the ductal localization, but galectin-1 showed variable
      expression in ductal and myoepithelial cells. In malignant tumors, most of the
      polymorphous low-grade adenocarcinomas and carcinoma ex-pleomorphic adenomas
      expressed both galectins, whereas adenoid cystic and acinic cell carcinomas
      showed dramatically reduced galectin-3 expression and heterogeneous galactin-1
      staining. Our data demonstrated altered localization and expression of galectin
      3, and to lesser extent, galectin-1 in salivary gland carcinomas. These findings
      may assist in the differential diagnosis of some salivary gland malignancies,
      especially when using small and limited fine-needle aspiration materials.

PMID- 10891536
TI  - Different mechanisms of acquired resistance to fluorinated pyrimidines in human
      colorectal cancer cells.
AB  - 5-Fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-trifluorothymidine
      (F3(d)Thd) are antimetabolites which are metabolized to their corresponding
      active forms which inhibit DNA synthesis via inhibition of thymidylate synthase
      (TS). To investigate ways of overcoming 5-FU-resistance, we established acquired
      resistant colorectal cancer cell lines against these three drugs by continuous
      and step-wise escalation of drugs, and analyzed the cytotoxicity and the
      mechanism of resistance to the drugs. When cells were incubated with the 3 drugs
      for 72 h, the resistance ratio to parental DLD-1 human colorectal tumor cells was
      65.2 for DLD-1/5-FU, 9.7 for DLD-1/FdUrd and 448.6 for DLD-1/F3(d)Thd cells. DLD
      1/5-FU cells did not show any cross-resistance against FdUrd and F(3)dThd.
      However, DLD-1/FdUrd cells showed 3- and 9-fold increased resistance to 5-FU and
      F3(d)Thd, respectively, and DLD-1/F3(d)Thd cells also showed about 90-fold
      resistance to FdUrd. Analysis of enzyme activities and gene expression associated
      with pyrimidine metabolism indicated that a significant decrease in orotate
      phosphoribosyltransferase activity in DLD-1/5-FU cells, a 7-fold increase of TS
      mRNA in DLD-1/FdUrd cells, and a 37-fold decrease in thymidine kinase activity of
      DLD-1/F3(d)Thd cells were the major mechanisms of drug resistance. These findings
      were closely associated with the cytotoxicity of 5-FU, FdUrd and F3(d)Thd against
      the established 5-FU-, FdUrd- or F3(d)Thd-resistant cells. When DLD-1/FdUrd cells
      expressing increased TS mRNA were treated with FdUrd and F3(d)Thd for only 4 h,
      the resistance ratios of DLD-1/FdUrd cells to parental DLD-1 cells were markedly
      different for FdUrd and F3(d)Thd, suggesting that the cytotoxicity with short
      time exposure to F3(d)Thd is due to a mechanism other than TS inhibition,
      although the cytotoxicity of F3(d)Thd in the short-time is low compared to that
      of long-time exposure. In conclusion, F3(d)Thd, an antimetabolite that inhibits
      TS activity, may be effective against 5-FU and/or FdUrd-resistance in colorectal
      cancer cells caused by amplification of TS and/or deletion of orotate
      phosphoribosyltransferase.

PMID- 10891537
TI  - Prolonged stable disease effects survival in patients with solid gastric tumor:
      analysis of phase II studies of doxifluridine.
AB  - We have previously reported that the survival time of most patients with solid
      tumors depend primarily on the length of the cytostatic phase rather than the
      extent of reduction induced. We analyzed a phase II study of doxifluridine, an
      intermediate metabolite of capecitabine, in gastric cancer to confirm our
      concept, because doxifluridine has shown low response rates (14%; 20/140) and
      long median survival times (371 days). The time to progression curves between the
      responder and stable disease were almost the same. The survival curves of the
      patients with stable disease of more than 90 days to progression (32 pts.) and
      responders were not significantly different.

PMID- 10891538
TI  - Neuropilin-2 expression affects the increased vascularization and is a prognostic
      factor in osteosarcoma.
AB  - Osteosarcoma is a malignant bone tumor characterized by hypervascularity.
      Neuropilins (NRPs), which is expressed by human tumor cells, is known to be a
      potent receptor for vascular endothelial growth factor (VEGF). We examined NRPs
      mRNA expression in 30 osteosarcomas. The osteosarcomas with NRP2 expression
      (n=24) showed a significantly increased vascularity (P<0.0014, Mann-Whitney U
      test). Osteosarcomas with NRP2 showed significantly poorer prognosis than those
      without NRP2 (P=0.016, Wilcoxon's test). These results suggest that NRP acts as a
      VEGF-amplifier in a paracrine or autocrine manner in the osteosarcoma. NRP2
      expression cooperatively promotes angiogenesis and growth in osteosarcomas with
      VEGF expression.

PMID- 10891539
TI  - Detection of genetic alterations in the human gastric cancer cell lines by two
      dimensional analysis of genomic DNA.
AB  - We examined genomic DNA from each of three human-derived gastric cancer cell
      lines, using the technique of restriction landmark genomic scanning (RLGS) which
      allows monitoring of approximately 2, 000 NotI landmarks. The resulting DNA spots
      from cancer cell DNA were compared with those in normal mucosa or gastric primary
      tumor. In all, 9 intense spots were detected from two of the three cancer cell
      lines. Two highly intensified spots were common in the two cancer cell lines and
      proven to be originated from DNA region containing the human c-myc proto-oncogene
      on chromosome 8. The degree of amplification of c-myc DNA was similar to each
      other and was estimated to be 60-fold as compared to those from normal mucosa
      DNA. On the basis of chromosome-assigned RLGS (CA-RLGS), other spots were
      assigned to each chromosome, such as one on chromosome 8, two each from
      chromosome 20, and three on one of chromosome 9-12. The remaining spot seems to
      be due to demethylation of a repetitive element. Twenty-four spot that were lost
      due to either homozygous deletion or methylation on corresponding NotI cleavage
      sites were commonly observed in all cancer cells. These spots were also assigned
      to each chromosome: one each from chromosome 2, 6, 7, 13, 14, 16, and 20, two
      each from chromosome 3 and 5, and nine from chromosome 9-12 by CA-RLGS. Many of
      the multi-copy spots corresponding to ribosomal RNA genes were greatly decreased
      due mainly to methylation on CpG islands along with minor rDNA variants,
      indicating that only minor rRNA genes may be silenced in these cancer cells.
      These results show that the present alterations detected by RLGS might be useful
      for identification of candidate genes inactivated or expressed unexpectedly in
      tumor development and tumor progression in the stomach.

PMID- 10891540
TI  - Targeted delivery of anticancer drugs with intravenously administered magnetic
      liposomes in osteosarcoma-bearing hamsters.
AB  - Although active targeting of anticancer drugs using magnetically responsive
      carriers is a very attractive treatment approach for solid tumors, successful
      results are limited. In particular, the therapeutic utility of intravenously
      administered magnetically responsive carriers has to date not been clearly
      established. The present study investigates magnetic liposomes designed to act as
      anticancer drug carriers, which can be effectively delivered to solid tumors via
      intravenous administration. Magnetic liposomes with incorporated adriamycin
      (magnetic ADR liposomes) were prepared by the reverse-phase evaporation method,
      and an in vivo study was carried out to assess the magnetic targeting of these
      liposomes to hamster osteosarcoma. The average diameter of liposomes thus
      prepared was 146 nm. Syrian male hamsters inoculated with osteosarcoma, Os515, in
      the right hind limb were studied 7 days after inoculation. After the hamsters had
      received an intravenous administration of either magnetic ADR liposomes or ADR
      solution (corresponding to 5 mg ADR/kg), the ADR concentrations in plasma, tumor,
      liver, lung, heart, and kidney were determined at designated time intervals.
      Administration of magnetic ADR liposomes under magnetic force using a permanent
      magnet (0.4 tesla) implanted in solid tumor produced an approximately 4-fold
      higher maximum ADR concentration in the tumor than did administration of ADR
      solution. The former administration modality induced an increase in ADR
      concentration in the liver and lung and a decrease in the heart compared with
      concentrations produced by the latter. The present results indicated that
      intravenously administered magnetic ADR liposomes can be used to effectively
      deliver ADR to osteosarcoma implanted with a magnet, as well as to the lung, a
      common site of metastases for osteosarcoma. Our results also suggest that this
      new treatment approach, which involves a combination of magnet implantation at
      the target site and intravenous administration of magnetic liposomes, can improve
      the clinical chemotherapy of solid tumors.

PMID- 10891541
TI  - Multipoint imprinting analysis in sporadic colorectal cancers with and without
      microsatellite instability.
AB  - Disrupted imprinting is implicated in certain tumorigenesis. Since aberrant
      methylation has been described for a majority of microsatellite instability (MSI)
      positive sporadic colorectal cancers, we have investigated alteration to the
      imprinting in 55 sporadic colorectal cancers with or without MSI. Loss of
      imprinting (LOI) of IGF2 and PEG1/MEST was observed in 42% and 35% of informative
      cancers, respectively. H19 expression was not detected in 24% of informative
      cancers. SNRPN and NDN retained monoallelic expression in all the cancers
      examined. These findings indicate no simultaneous disruption of the imprinted
      genes. LOI of IGF2 and PEG1/MEST was also observed in colorectal mucosa from
      almost all the patients with LOI in tumor tissue. Moreover, MSI-positive
      colorectal cancers exhibit LOI of IGF2 with a high frequency compared to MSI
      negative cancers (P=0.013). These observations, consistent with a previous
      report, establish an association between LOI of IGF2 and MSI in colorectal
      cancers and provide insight into susceptibility of tumor development.

PMID- 10891542
TI  - Binary/ternary combined effects of vitamin K3 with other antitumor agents in
      nasopharyngeal carcinoma CG1 cells.
AB  - Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Taiwan. To improve the
      treatment of NPC, we have extensively searched for effective combination
      chemotherapies. Our previous studies indicated that vitamin K3 (VK3) inhibits the
      growth of NPC CG1 cells in vitro. In this study, we further studied the
      binary/ternary combined effects of VK3 with other anticancer drugs against NPC
      cells. The antitumor effects of different VK3 combinations against CG1 cells were
      determined by using MTT assay, and the combined effects were evaluated by a
      taibologram, a modified isobolographic method being developed in our laboratory
      for the analyses of binary/ternary combinations of anticancer agents. Binary
      combinations of VK3 with doxorubicin (DOX), vinblastine (VBL), or 5-fluorouracil
      (5-FU) result in synergistic effects. For three-drug combinations, a remarkable
      synergy was found in the combination of VK3, VBL, and 5-FU. These in vitro
      results will provide useful information not only for further mechanistic studies
      and but also for future clinical trials of VK3-based cancer chemotherapy of NPC.

PMID- 10891543
TI  - Overproduction of IL-8 results in suppression of bone metastasis by lung cancer
      cells in vivo.
AB  - HARA-B cells were established from the bone lesion in nude mice formed after an
      intracardiac inoculation of the human lung cancer-derived cells (HARA), and
      production of IL-8 in HARA-B cells was decreased as compared to that in the
      parental HARA cells. This suggests a possible relationship between IL-8
      production and bone metastasis. Thus, we examined the effect of IL-8 on bone
      metastasis using HARA-B cells transfected with experimental (IL-8-cDNA) and/or
      control plasmid in the experimental bone metastasis model in nude mice. Growth
      rates of both cells in vitro were similar. Control cells developed radiologically
      detectable bone metastases in 50% of nude mice tested, whereas experimental cells
      did not develop bone metastases. Osteoclastic bone resorption is an important
      step in the process of bone metastasis, and IL-8 possesses an inhibitory effect
      on osteoclastic bone resorption. These results suggest that IL-8 suppresses bone
      metastasis, which might be attributed to the inhibitory effect of IL-8 on
      osteoclastic bone resorption.

PMID- 10891544
TI  - C-Cbl protein in human cancer tissues is frequently tyrosine phosphorylated in a
      tumor-specific manner.
AB  - To search for the signaling pathway relevant to the tumorigenesis in human, we
      examined the expression and tyrosine phosphorylation of c-cbl proto-oncogene
      product, c-Cbl, in various human cancer cell lines and surgical specimens. In
      cells derived from human cancer, we found constitutive tyrosine phosphorylation
      of c-Cbl protein, whereas its phosphorylation was undetectable in control ECV304
      cells. Expression and tyrosine phosphorylation of c-Cbl was also examined in
      various surgical specimens. Thirty-six surgical specimens obtained from human
      tumor tissues were studied: 9 gastric carcinomas, 10 colon carcinomas, 6 renal
      carcinomas, 2 hepatomas, 2 brain tumors, 2 uterus tumors, 1 breast carcinoma, 1
      thyroid tumor, 1 bladder tumor and 2 lung carcinomas. We found tyrosine
      phosphorylation of c-Cbl protein in 12 cases (33%) of these tumor tissues in a
      tumor-specific manner. These results suggest the importance of c-Cbl signaling in
      tumorigenesis in human.

PMID- 10891545
TI  - Prognostic impact of telomerase activity in patients with neuroblastoma.
AB  - Neuroblastoma is one of the most common malignant neoplasms occurring among
      children. The prognosis for this disease is strongly associated with age, disease
      stage, histology, and some biologic features. It has been reported that
      telomerase, a ribonucleoprotein enzyme, which maintains the telomere length in
      immortal cells, is related to disease stage and other biologic features. The
      purpose of this study was to evaluate the prognostic value of telomerase activity
      compared to TrkA expression in 65 patients with neuroblastoma. Telomerase
      activity and TrkA expression were examined in tissue samples collected between
      1980 and 1994 from 65 patients by polymerase chain reaction-based telomerase
      activity. TrkA expression was examined by immunoblotting using a rabbit anti
      gp140 proto-trk polyclonal antibody. Low telomerase activity was found in 22 of
      30 (73.3%) patients with Stages 1, 2, or 4S neuroblastomas; 7 of 13 (53.8%) with
      Stage 3; and 8 of 22 (36.3%) with stage 4; no telomerase activity was detected in
      7 of 22 (31.8%) patients with Stage 4 neuroblastoma. The 5-year event-free
      survival (EFS) rate was 86.5% for patients with low telomerase activity, while it
      was 53.8% for patients with high telomerase activity. By the combination of
      telomerase activity and TrkA expression, the 5-year EFS rate was highest among
      patients with a high TrkA expression and a low or non-existent telomerase
      activity (91.7%), and it was lowest among patients with a low TrkA expression and
      a high telomerase activity (29.6%). Thus, it appears that telomerase activity
      would be a useful prognostic factor for neuroblastoma, especially when used in
      combination with the TrkA expression.

PMID- 10891546
TI  - A new human malignant peripheral nerve sheath tumour-cell line, HS-sch-2,
      harbouring p53 point mutation.
AB  - Only a few human malignant peripheral nerve sheath tumour (MPNST)-cell lines have
      been reported, and their characteristics have not been fully established. In this
      study, we established a new human cell line, HS-Sch-2, from an MPNST of the
      ordinary type which arose in a 54-year-old woman without von Recklinghausen's
      disease. This cell line was characterized by chromosome analysis,
      immunohistochemistry, ultrastructural examination, and direct sequencing of the
      p53 gene. The HS-Sch-2 cells have grown for more than 48 months in vitro, and
      exhibited hypotriploid karyotypes with complex chromosome abnormalities lacking a
      specific pattern. Histological features of the heterotranplanted nude mouse
      tumours were essentially the same as those of the original MPNST, with positive
      reactions for S-100 protein and neuron-specific enolase but not for epithelial
      membrane antigen, fibronectin or CD34. Ultrastructural examination in vivo
      revealed intricate interdigitation of long cytoplasmic processes and basal lamina
      like structures. In addition, direct sequencing of the p53 gene detected a point
      mutation from CGT to CAT at codon 273 in exon 8. This HS-Sch-2 cell line, which
      exhibits distinctive morphological characteristics of MPNST and a p53 point
      mutation, will be useful for biological and pathological investigations of MPNST.

PMID- 10891547
TI  - Ruthenium-based compounds and tumour growth control (review).
AB  - Heavy metals have often been represented, as an uncertain entity related to renal
      and other risks of toxicity. In favour of this thought there are several lines of
      evidence, first of all traffic pollution, other evidence that metals such as
      arsenite, mercury, cadmium or even iron or radioactive heavy metals, that may be
      introduced into the body by accident, have been responsible of well known
      pathologies (for example saturnism with lead) or acute toxicity. Therefore, the
      biological and medical literature have debated on this subject, mainly from the
      toxicological point of view, rather than studying possible advantages that might
      come from compounds based on these metals. Exceptions are represented by studies
      on the role of metal ions in the biochemistry of enzymes and energy production
      and, although with less emphasis, on their possible use for correcting metabolic
      malfunctions. Ruthenium, as a metal, has received an even poorer interest and
      besides the use in histology, neither ruthenium ions nor ruthenium compounds have
      a clear place in medicine and biology. Nevertheless, since the middle seventies,
      many studies have been published, showing in a convincible and repetitive manner,
      the possible advantages of ruthenium as a base for new competitive drugs. The aim
      of this review is therefore that of critically examining the past and the actual
      work on ruthenium compounds with emphasis on their proposed role in cancer
      therapy.

PMID- 10891548
TI  - Down-regulation and change in subcellular distribution of receptors for
      luteinizing hormone-releasing hormone in OV-1063 human epithelial ovarian cancers
      during therapy with LH-RH antagonist Cetrorelix.
AB  - The inhibition of growth of various hormone-dependent cancers by analogs of
      luteinizing hormone-releasing hormone (LH-RH) may be exerted in part through
      receptors for LH-RH present on tumor cells, but the direct mode of action of LH
      RH agonists and antagonists is still not completely understood. The aim of this
      study was to investigate the effects of agonist [D-Trp6]LH-RH and antagonist
      Cetrorelix, administered s.c. at a dose of 100 microg/day for 3 weeks on the
      binding characteristics and subcellular localization of receptors for LH-RH in OV
      1063 human epithelial ovarian cancers xenografted into nude mice. Using
      radioligand binding studies, following in vitro desaturation, we demonstrated the
      presence of specific, high affinity binding sites for LH-RH in both cell membrane
      and nuclear fraction of OV-1063 tumors. Treatment with Cetrorelix, but not [D
      Trp6]LH-RH, caused about 60% reduction (p<0. 01) in tumor volume and weight. [D
      Trp6]LH-RH decreased the number of LH-RH receptors on OV-1063 tumor membranes by
      44% after 14 days (p<0.01), and the concentration of receptors remained at that
      level on day 21. The maximal binding capacity of receptors for LH-RH in the
      nuclei was significantly higher (p<0.05) after 3 weeks of treatment with [D
      Trp6]LH-RH. Cetrorelix decreased the concentration of membrane receptors for LH
      RH by 53% (p<0.01) after 14 days and the levels on day 21 were even lower,
      showing a 70% reduction (p<0. 01). In contrast, the number of LH-RH binding sites
      in the nuclear pellet was significantly increased (p<0.01) by Cetrorelix at that
      time. Our results demonstrate for the first time that the down-regulation of LH
      RH receptors on the cell membranes of OV-1063 human ovarian cancers after therapy
      with antagonist Cetrorelix or agonist [D-Trp6]LH-RH is associated with an
      increase in receptor concentration in the nuclei. These phenomena could be
      related to the internalization and subcellular translocation of receptors in
      these tumor cells.

PMID- 10891549
TI  - Computer based analyses of the 5'-flanking regions of selected genes involved in
      the nucleotide excision repair complex.
AB  - We have previously observed that the mRNA of selected genes involved in
      nucleotide excision repair appear to be coordinately expressed in human tissues
      from patients with ovarian cancer, testicular cancer, malignant brain tumors, and
      other malignancies. Such genes include ERCC1, XPA, XPB, XPD, XPF, and XPG.
      Coordinate mRNA expression appears to be most impressive in non-malignant
      tissues. We therefore began to explore possible reasons why such coordinate
      expression should occur. DNA sequences for the above noted genes were obtained
      from GeneBank. Two different software programs were applied to the DNA sequence,
      to the area 5' to the start of exon I of each gene. Analyses were performed by
      computer. The length of the 5' area assessed, was based on previous reports that
      determined what portion of the genomic sequence comprised the 5' UTR of the
      promoter of the respective gene. Based on this approach, potential DNA binding
      sites for no less than three dozen proteins, were identified in the 5'-flanking
      region of each of the NER genes studied. For each gene, potential binding sites
      for activator proteins and for repressor proteins were identified. The 5'
      flanking regions for each gene noted above, had binding sites in common for 14
      proteins with transcription modulatory activity. Eleven of these proteins are
      known for activator activity; two are reported to have repressor activity, and
      one has both repressor and activator function. These data suggest a possible
      molecular basis for the previously observed coordinate mRNA expression of
      selected NER genes in human tissue specimens.

PMID- 10891550
TI  - The detection of telomerase activity in patients with adenocarcinoma of the
      pancreas by fine needle aspiration.
AB  - Telomerase activation in differentiated cells is associated with cell
      immortalization. Detection of telomerase expression in cancer provides a
      potential biomarker to be evaluated in the diagnosis and prognosis of cancer
      patients. Analysis of telomerase activity in biopsy specimens may serve as a
      useful marker for the diagnosis of pancreatic adenocarcinoma. This study was
      conducted to determine if telomerase could be detected in fine needle aspirates
      from patients with pancreatic carcinoma. The telomeric repeat amplification
      protocol (TRAP) assay was used to determine telomerase activity from pancreatic
      cancer cell lines, paired tumor/normal human pancreatic tissues and specimens
      obtained at the time of diagnostic fine-needle aspiration (FNA) biopsies. In this
      report, we demonstrate that: i) telomerase activity is present in pathologically
      confirmed pancreatic cancer specimens, but absent in matched adjacent areas of
      normal pancreatic tissues; ii) telomerase activity is present in FNA samples
      obtained at the time of CT-guided FNA of pancreatic adenocarcinomas; and iii)
      this activity can be detected in material normally discarded during FNA slide
      preparation. Activation of telomerase can be identified in FNA specimens obtained
      at the time of routine cytologic diagnosis. These findings may be useful for
      further diagnostic or therapeutic investigations of telomerase activity in
      pancreatic carcinoma.

PMID- 10891551
TI  - Overexpression of P-glycoprotein is associated with a decreased mitochondrial
      transmembrane potential in doxorubicin-selected K562 human leukemia cells.
AB  - We tested the hypothesis of whether overexpression of P-glycoprotein (Pgp) could
      be coupled with changes in specific mechanisms of antioxidant defense (in
      particular, transition of mitochondrial transmembrane potential, MTP) in tumor
      cells chronically exposed to anticancer drugs known to exert their cytotoxicity
      via oxidative stress. We show elevation of Pgp associated with decreased MTP in
      doxorubicin-selected K562Dox subline as compared with parental K562 cells. The
      low MTP was not due to a fewer number of mitochondria in K562Dox cells, nor was
      it associated with altered content of Bcl-XL protein. We discuss a model for
      coordinated up-regulation of Pgp and MTP transition in cells that survived
      chemotherapy-induced oxidative stress.

PMID- 10891552
TI  - The inhibitory effect of cisplatin in combination with irradiation on lung tumor
      cell growth is due to induction of tumor cell apoptosis.
AB  - Chemoradiation is becoming an important method of treatment of advanced lung
      cancer. Although many studies have demonstrated the efficacy of chemoradiation
      against lung tumors, the mechanism of its effect is still poorly understood. In
      this study, we analyzed the combined effect of cisplatin (CDDP) and irradiation
      on human lung cancer cell lines (PC-9 and Lu 134A) in vitro using MTT assay and
      isobologram analysis. To study whether the combined effect is due to induction of
      tumor cell apoptosis, we further quantified the nuclear fragmentation of tumor
      cells by flow cytometric analysis. Our study revealed that a combination of
      cisplatin and irradiation had an additive inhibitory effect on both PC-9
      (adenocarcinoma) and Lu 134A (small cell carcinoma) tumor cell growth. Cisplatin
      improved the sensitivity of tumor cells to irradiation. The use of both cisplatin
      and irradiation doses could be reduced without decreasing the inhibitory effect.
      The additive inhibitory effect was correlated positively with the levels of tumor
      cell nuclear fragmentation. We concluded that combination treatment with
      cisplatin and irradiation is effective against lung tumors, not only small cell
      carcinoma but also non-small cell carcinoma, and the inhibitory effect was due to
      induction of tumor cell apoptosis.

PMID- 10891553
TI  - Gamma-radiation-induced single cell DNA damage as a measure of susceptibility to
      lung cancer: a preliminary report.
AB  - The comet assay is a sensitive and rapid method for detecting DNA single-strand
      and double-strand breaks and the individual cell's DNA repair profile. This pilot
      study was designed to determine whether the comet assay could measure inherited
      susceptibility to lung cancer. We applied the comet assay in the alkaline
      condition to test the DNA damage in gamma-irradiated and untreated cultured
      peripheral blood lymphocytes of 31 cases with previously untreated lung cancer
      and 39 controls. For each culture, 200 consecutive cells were examined and the
      number of cells with DNA uncoiling under electrophoresis (<comet cells>) was
      recorded. The comet tail length (the radius of the nucleus plus the length of the
      migrated DNA) at 400-fold magnification was measured for the first 50 identified
      comet cells. The mean number of induced comet cells was significantly higher in
      cases (96.0+/-45.7) than matched controls (68.9+/-35.8) (P<0.05). However, no
      significant difference was observed in induced comet tail length between cases
      and controls. When we categorized the number of comet cells by the 75th
      percentile value in the controls, a higher number of comet cells was associated
      with significantly increased risk for lung cancer [odds ratio = 4.8 (confidence
      intervals of 1.5, 15.2)] after adjustment for age, sex, ethnicity and smoking
      status. The number of gamma-irradiation-induced comet cells (r=0.499, P<0.05) and
      comet tail length (r=0.520, P<0.05) correlated with the results on a previously
      reported lung cancer susceptibility marker, bleomycin sensitivity. Also, the
      number of gamma-irradiation-induced comet cells correlated with the results of
      the benzo[alpha]pyrene diol epoxide mutagen sensitivity assay, which quantifies
      induced chromatid breaks (r=0.275, P<0.05). The comet assay might be a simple and
      inexpensive tool for detecting genetic susceptibility to lung cancer.

PMID- 10891554
TI  - Profiling the immune responses in patient sera with peptide and cDNA display
      libraries.
AB  - Peptide and cDNA phage display libraries can be used to determine the
      specificities of antibodies present in the whole sera of patients where
      information about the parental antigens is unknown. In this respect, patient
      serum antibody binding ligands have been identified. Such ligands would
      facilitate the design of diagnostic assays and therapeutic vaccines. In the case
      of cancer, this novel technology is expected to improve our understanding of the
      immune responses against tumour cells and to discriminate between autoantigen and
      true tumour specific antigens. Here, we review work on how peptide and cDNA phage
      display libraries can be used to address the specificity of the immune responses
      in patients with autoimmune diseases and cancer.

PMID- 10891555
TI  - The effect of glycosaminoglycans and proteoglycans on lipid peroxidation.
AB  - Recent investigations show that glycosaminoglycans (GAGs) and proteoglycans (PGs)
      have the ability to affect lipid peroxidation, one the best characterized forms
      of free radical mediated biological damage. A protective effect of these
      extracellular matrix (ECM) components has been demonstrated in various
      experimental systems, including fatty acids and liposomes, where oxidation was
      induced by transition metals, including copper and iron. The effect was specific
      and dependent on the type and structural features of GAGs and PGs. The mechanism
      of peroxidation inhibition was likely to be dependent, at least to a large
      extent, on the sequestration of transition metals by GAG chains. Thus, it is
      conceivable that GAGs in the ECM and in the pericellular space may contribute to
      protecting cells against free radical damage. It is of particular interest that
      in certain tissues (cornea and aorta) aging was associated with a decrease of
      content of the GAGs which were most effective as anti-oxidant. This suggests that
      age-induced modifications of ECM composition in certain tissues may increase the
      susceptibility to oxidative stress. The investigation on the effect of GAGs on
      lipoprotein oxidation led to apparently conflicting results. An interesting
      reconciliation is possible, according to which GAGs exerted their protective
      effect under experimental conditions not compatible with the formation of
      lipoprotein-GAG complexes; rather, lipoproteins exhibited increased
      susceptibility to metal-catalyzed oxidation (MCO), possibly due to structural
      modifications of the particle after binding to GAGs or PGs. This process is
      likely to occur in the intimal matrix of arteries.

PMID- 10891556
TI  - Relationship between p53 overexpression and the proliferative activity in
      hepatocellular carcinoma.
AB  - Relationship between p53 protein overexpression and clinicopathological findings
      and the proliferative activity was studied in 50 cases of hepatocellular
      carcinoma (34 biopsy and 16 surgically resected cases) using
      immunohistochemistry. Overexpression of p53 was observed in 26.5% of biopsy cases
      and 31. 3% of surgically resected cases. Investigation of the relationship
      between the p53-positive rate and the clinical stage of HCC showed that it was
      significantly higher in Stage IV (the most advanced cancer; 54.5%) than in Stage
      I/II/III (13.0%) (p<0.05). Examination of the relationship between the p53
      positive rate and tumor differentiation in the biopsy cases showed that p53 was
      positive in 9.1% of well differentiated carcinomas, 21.4% of moderately
      differentiated carcinomas, and 55.6% of poorly differentiated carcinomas,
      indicating that p53 positivity increased as tumors became less differentiated.
      The p53-positive rate of poorly differentiated carcinoma (55.6%) was
      significantly higher than that of well and moderately differentiated carcinoma
      (16.0%) (p<0.05). In the surgically resected cases, p53 overexpression tended to
      be more frequent in the less differentiated parts of each tumor nodule. In cases
      with nodule in nodule pattern of HCC, the p53-positive rate was different among
      nodules with the same level of differentiation. Examination of tumor cell
      proliferative activity using the proliferating cell nuclear antigen L.I. showed
      that this indicator was significantly higher in the p53-positive tumors than in
      the p53-negative tumors (52.7+/-32.4% vs. 32.4+/-15.3%: p<0.05). These results
      suggest that p53 overexpression may be involved in determining the
      dedifferentiation and the proliferative activity of HCC. Examination of the
      surgically resected cases confirmed that p53 overexpression became heterogeneous
      during the multistep carcinogenesis and growth process of HCC, which is
      considered to develop from a single cell. This finding suggests that p53
      overexpression may be involved in tumor progression.

PMID- 10891557
TI  - Effects of D-mannoheptulose and its hexaacetate ester on hormonal secretion from
      the perfused pancreas.
AB  - D-mannoheptulose was recently proposed to be transported into cells by GLUT2,
      whereas its hexaacetate ester may cross the plasma membrane without requiring the
      intervention of a specific carrier system. In the light of these proposals, the
      effects of unesterified D-mannoheptulose and D-mannoheptulose hexaacetate upon
      hormonal secretion by the perfused rat pancreas were now investigated.
      Unesterified D-mannoheptulose (1.7 mM) inhibited insulin release and, in most
      cases, somatostatin output, whereas it augmented glucagon secretion by pancreases
      exposed to D-glucose (3.3 mM) in the presence of the dimethyl ester of succinic
      acid (SAD, 10.0 mM). The heptose failed, however, to affect hormonal secretion in
      the sole presence of SAD. D-mannoheptulose hexaacetate (also 1.7 mM) reproduced,
      within limits, the effects of unesterified D-mannoheptulose in pancreases exposed
      to both D-glucose and SAD. In addition, however, the ester displayed a positive
      effect upon the secretion of the three hormones, even in the sole presence of
      SAD. These findings support the view that monosaccharide esters may affect the
      secretion of pancreatic hormones in a dual manner, linked to both the metabolic
      response to their glucidic moiety and a direct effect of the ester itself.
      Moreover, they reveal that unesterified D-mannoheptulose is able to antagonize
      the effect of D-glucose upon hormonal secretion even in cells claimed not to
      contain GLUT2. The modality by which D-mannoheptulose apparently gains access to
      the cytosol of these cells remains to be elucidated.

PMID- 10891558
TI  - Binding of topo I to PARP I - antibody immunocomplex.
AB  - It is frequently quoted in the literature that the cellular role of PARP I is its
      participation in the recognition of single strand breaks of genomic DNA (l.c.1).
      Although there is little doubt that PARP I can be made to respond powerfully as
      an factor in the recognition of DNA damage, it seems unlikely that this
      auxilliary, or telelogically defined, role of this highly abundant nuclear
      protein exhausts its physiologic cellular function. We have reported that Topo I
      is greatly activated by its association with PARP I (J Mol Med 5: 533-540, 2000).
      Translation of this in vitro model experiments to physiologic conditions was
      accomplished by the demonstration of the quantitative binding of Topo I to a PARP
      I - antibody complex, as reported here. This experiment demonstrates for the
      first time that the colligative action of PARP I can regulate a highly
      significant cellular process, the control of readability of genomic DNA, i.e.,
      gene expression, without the artificiality of induced DNA damage.

PMID- 10891559
TI  - Participation of a MEK-independent pathway in MAP kinase activation and
      modulation of cell growth in mouse hepatoma cell lines.
AB  - The mechanism of cell growth was investigated in GIT medium-supplemented in vitro
      assay using high and low metastatic mouse hepatoma cell sublines, G-5 and G-1,
      respectively. G-5 cells exhibited high growth rate compared to G-1 cells. The PI3
      kinase inhibitor LY294002 and P70 S6 kinase inhibitor rapamycin partially blocked
      both G-1 and G-5 cell growth, suggesting that these two kinases are involved in
      hepatoma cell growth. In contrast, the MEK1 inhibitor PD98059 partially blocked G
      5 cell growth but not G-1 cell growth. MAP kinases (MAPK) in both G-1 and G-5
      cells were indistinguishably phosphorylated, yet MEK-dependent MAPK activation
      was observed only in G-5 cells. In G-1 cells, MAPK was phosphorylated in a manner
      not connected to MEK activation. Thus, the low degree of cell growth in G-1 cells
      was attributable to disruption of the MEK-dependent MAPK cascade. However, the
      molecular mechanism whereby MAPK phosphorylation does not parallel MAPK
      activation in G-1 cells remains unknown. Here, we suggest that there may be an as
      yet unidentified MAPK phosphorylation pathway in malignantly transformed cells,
      which may affect in vivo cell growth and metastatic capacities of cancers.

PMID- 10891560
TI  - Expression of genes involved with cell cycle control, cell growth and chromatin
      modification are altered in hepatoblastomas.
AB  - Hepatoblastoma is a rare pediatric liver tumor. While much progress has been made
      in the treatment of the disease, very little is known about the moleculer events
      underlying the pathogenesis of this disease. We sought to investigate a series of
      hepatoblastomas for alterations in gene expression patterns with emphasis on
      important cell regulatory genes, including chromatin modifying enzymes, cyclin
      dependent kinase inhibitors, growth factors, oncogenes and cell cycle regulators.
      Total RNA was extracted from a series of sporadic hepatoblastomas with matched
      normal liver, some unmatched tumors and fetal livers, and gene expression was
      measured for various genes using RNase Protection Analysis (RPA). The results of
      this analysis show that the expression of many important regulatory genes are
      distinctly altered in these tumors, and a subset of tumors can be distinguished
      on the basis of these gene expression differences and histopathological features.
      Because the molecular events underlying the pathogenesis of this rare tumor are
      so poorly understood, this study represents a first step in determining some of
      the possible mechanisms involved which may provide future avenues of research.

PMID- 10891561
TI  - Effects of D-mannoheptose and D-glycero-D-gulo-heptose upon D-glucose metabolism
      and insulinotropic action in rat pancreatic islets and D-glucose phosphorylation
      by hexokinase isoenzymes: comparison with D-mannoheptulose.
AB  - The possible use of D-mannoheptose or D-glycero-D-gulo-heptose as substitute of D
      mannoheptulose for specific inhibition of D-glucose phosphorylation, metabolism
      and insulinotropic action was investigated in the present study. The two
      aldoheptoses failed to duplicate the effect of D-mannoheptulose upon the
      phosphorylation of D-glucose by yeast hexokinase, bovine heart hexokinase or
      human B-cell glucokinase. They were poorly phosphorylated by the low-Km
      hexokinase isoenzymes or liver B-cell glucokinase. D-mannoheptose failed to
      reproduce the inhibitory action of D-mannoheptulose upon D-glucose metabolism by
      isolated rat pancreatic islets. Whilst D-glycero-D-gulo-heptose failed to affect
      glucose-induced insulin release, D-mannoheptose slightly enhanced glucose-induced
      insulin release when tested at low concentrations (0.75-1.5 mM) and progressively
      decreased insulin output at higher concentration (3. 0-20.0 mM) in islets exposed
      to a high (16.7 mM), but not physiological (8.3 mM), concentration of D-glucose.
      D-mannoheptose, however, also caused a modest inhibition of insulin release
      evoked by 2-ketoisocaproate. It is concluded, therefore, that neither D
      mannoheptose nor D-glycero-D-guloheptose can be considered as suitable
      substitutes of D-mannoheptulose.

PMID- 10891562
TI  - Detection of ornithine transcarbamylase deficiency heterozygotes by measuring of
      urinary uracil.
AB  - The importance of detecting heterozygosity for X-linked ornithine
      transcarbamylase deficiency is well known. Although the DNA analysis and the
      allopurinol loading tests are commonly used for this purpose, both methods
      require complicated procedures. In order to establish a simple test for detecting
      female heterozygotes, we examined the uracil and orotic acid in single-voided
      urine samples from 70 healthy women, and from 12 asymptomatic females with
      ornithine transcarbamylase deficiency. Based on the results of healthy women, we
      were able to determine a screening cut-off line of 11.9 micromol/mmol creatinine
      (mean +/- 1SD in logarithmic form) for uracil. Using this cut-off line, the
      sensitivity of OCT heterozygotes was 100%. We were also able to establish a
      second cut-off line of 28.9 micromol/mmol creatinine (mean +/- 3SD in logarithmic
      form) for diagnosis. Using this second cut-off line, the specificity of OCT
      heterozygotes was 100%. Our study has shown that the measurement of urinary
      uracil is a relatively simple and effective method for detecting female
      heterozygotes.

PMID- 10891563
TI  - Carbon tetrachloride treatment induces anorexia independently of hepatitis in
      rats.
AB  - Oxidative stress is involved in the development of anorexia. In the present
      study, we examined the possible involvement of anorexia in oxygen radical-induced
      hepatitis. A low dose of carbon tetrachloride (1 ml/kg of a 1:1 solution with
      olive oil) was orally administered to rats with and without food restriction. In
      rats with food restriction, carbon tetrachloride treatment induced hepatitis and
      reduced the body weight gain. In contrast, carbon tetrachloride treatment did not
      induce hepatitis in rats without food restriction, but the body weight was
      decreased. In these rats, the loss of body weight was accompanied by a decrease
      in food intake. The present results indicate that the administration of a low
      dose of carbon tetrachloride to rats without food restriction induced anorexia
      independently of hepatitis.

PMID- 10891564
TI  - Co-transduction of herpes simplex virus thymidine kinase gene and human
      interleukin-2 gene into mouse ovarian cancer cell line, OVHM.
AB  - We studied the thymidine kinase (TK) gene and the interleukin (IL)-2 gene co
      transduction into tumor cells for a possible strategy of cancer gene therapy. A
      murine ovarian cancer cell line, OVHM, was retrovirally transduced with the TK
      (OVHM/TK) or the IL-2 gene (OVHM/IL-2). The TK or IL-2 expression was permanent
      in OVHM/TK or OVHM/IL-2. OVHM/TK cells were susceptible to gancyclovir (GCV) in
      vitro, and their intraperitoneal growth was completely regulated with GCV
      administration. The bystander effect was not observed in vitro and in vivo in
      this model, and only the marginal emergence of immune involvement was observed in
      the OVHM/TK-cured mice with GCV. OVHM/IL-2 cells produced IL-2 biologically
      active to be immunogenic, but still tumorigenic to kill the mice when inoculated
      intraperitoneally. Then, OVHM/TK cells were co-transduced with the IL-2 gene to
      establish OVHM/TK/IL-2 cells. OVHM/TK/IL-2 cells were also susceptible to GCV and
      transiently produced active IL-2. A significant resistance against the challenge
      of parental tumor cells was observed in the mice that were inoculated with
      OVHM/TK/IL-2 cells and cured with GCV administration. It is suggested that tumor
      cells transduced with both TK and IL-2 genes could be regressed with GCV
      administration with subsequent generation of immune activation in the host. Since
      the bystander effect may not always be a common phenomenon in gene therapy using
      the TK gene, this type of combination may be advantageous in the clinical
      application of gene therapy for human cancers.

PMID- 10891565
TI  - The gene of Ca2+-binding protein regucalcin is highly conserved in vertebrate
      species.
AB  - Regucalcin is a Ca2+-binding protein, which plays a regulatory role in liver cell
      functions related to Ca2+. In this study we have cloned cDNA for regucalcin from
      rabbit, bovine, chicken and toad livers by using rapid amplification of cDNA ends
      (RACE) method. The nucleotide and amino acid sequences of them are compared with
      published human, rat and mouse sequences. Comparison analysis revealed that the
      nucleotide sequences of regucalcin from seven vertebrate species were highly
      conserved in their coding region. The overall regucalcin proteins in these
      species consisted of 299 amino acids, and they had 69.9-91.3% identity.
      Furthermore, phylogenetic analysis showed that regucalcin in seven species
      appears to form a single cluster. This study demonstrates a great conservation of
      the regucalcin genes throughout evolution.

PMID- 10891566
TI  - Activation of glycogen synthase a in hepatocytes exposed to alpha-D-glucose
      pentaacetate.
AB  - The effects of alpha-D-glucose pentaacetate (1.7 mM) upon glycogen synthase a
      activity and lactate output were examined in rat hepatocytes incubated at
      increasing concentrations of D-glucose. The ester enhanced the activity of
      glycogen synthase a at all concentrations (2.8, 4.0 and 8.0 mM) of D-glucose,
      which itself provoked a concentration-related increase in enzymatic activity.
      Likewise, the output of lactate augmented at increasing concentrations of D
      glucose. However, alpha-D-glucose pentaacetate failed to cause a further increase
      in lactate output, the trend being even towards a lower production of lactate in
      the presence than absence of the ester. These findings suggest that the
      activation of glycogen synthase a by alpha-D-glucose pentaacetate and the
      subsequent increase in glycogen synthesis are sufficiently pronounced to prevent
      the increase in glycolysis otherwise expected from the generation of unesterified
      D-glucose from the same ester. Such a situation, which differs from that
      previously documented in pancreatic islet cells, could be favourable in the
      perspective of using alpha-D-glucose pentaacetate as a novel insulinotropic, and
      hence hypoglycaemic, tool in the treatment of non-insulin-dependent diabetes
      mellitus.

PMID- 10891567
TI  - Molecular alterations of E-cadherin gene: possible role in human bladder
      carcinogenesis.
AB  - E-cadherin is a transmembrane glycoprotein which mediates a calcium dependent
      homophilic interaction among epithelial cells. The altered expression and gene
      mutations of E-cadherin adhesion molecule have been frequently observed in
      various tumors. Several invasive carcinomas showed cell-cell adhesion loss
      although the tumor cells expressed considerable amounts of E-cadherin protein.
      The purpose of this study was to evaluate the role of E-cadherin gene alterations
      in genesis and progression of bladder carcinoma by mutation analysis of coding
      region, expression analysis and microsatellite instability at E-cadherin
      chromosome locus. We analyzed 30 bladder carcinoma (28 transitional and 2
      squamous cell carcinoma) at different stage and grade. The mutation analysis
      showed that in one case there was a presence of a point mutation at codon 846
      that consisted of a G (AGC) to C (ACC) transversion resulting in the replacement
      of R to T. In another sample the sequence analysis revealed a same-sense mutation
      at the codon 785 (AAC - AAT). The study of E-cadherin mRNA by Northern blot
      analysis showed that there were no differences of mRNA levels between tumor and
      normal mucosa samples. We noted that invasive and anaplastic tumors showed a
      trend to loss of expression, even if we did not find any statistically
      significant differences. The microsatellite analysis showed the presence of
      genomic instability in proximity of the E-cadherin gene. Nine out of 30 (30%)
      specimens presented molecular alterations in at least one out of 2 loci (D16S260
      and D16S301) analyzed. The comparison between microsatellite mutations and
      clinical-histopathological parameters revealed a higher number of alterations in
      invasive respect to superficial tumors (p=0.014). On the other hand, there were
      no statistical differences regarding the correlation with pathological grade.
      These observations, which, nevertheless, need to be confirmed in a larger number
      of patients, suggest that alterations of E-cadherin gene may be related to
      pathobiology of bladder cancer development and clinical progression.

PMID- 10891568
TI  - Progesterone inhibits inducible nitric oxide synthase mRNA expression in human
      intestinal epithelial cells.
AB  - Progesterone inhibits the transcription of inducible nitric oxide (NO) synthase
      (iNOS) in murine macrophages. The effect of female sex steroids on the regulation
      of the human iNOS gene, which shares no identity in the 5' and 3' non-coding
      regions with its murine homolog, is unknown. Pretreatment of the human
      enterocytic cells DLD-1 and Caco-2BBe with estradiol or dexamethasone had no
      effect on NO production induced by IL-1beta, LPS, and IFN-gamma. In contrast, NO
      production was inhibited by progesterone when administered as a pre-treatment or
      as a post-treatment 6 h after cytokine exposure (IC50 in DLD-1 and Caco-2BBe
      cells = 66 and 45 microM). Progesterone pre-treatment inhibited cytokine-induced
      iNOS mRNA expression by 66% and 58% in DLD-1 and Caco-2BBe cells, respectively.
      Nuclear run-on analysis demonstrated that progesterone did not inhibit cytokine
      induced iNOS transcription. These data imply that progesterone inhibits iNOS mRNA
      expression at a post-transcriptional level, which is the dominant mode of iNOS
      regulation in human enterocytes. Since iNOS-derived NO production has been
      related to the inflammatory and tumorigenic response of progesterone-receptor
      bearing tissues, the repression of iNOS mRNA expression by a female sex steroid
      could play an important role in the regulation of a broad range of physiologic
      processes.

PMID- 10891569
TI  - Corneocyte desquamation.
AB  - Corneocyte desquamation at the skin surface is a complex biologic event which is
      normally regulated for providing an inconspicuous shedding of single corneocytes.
      When altered, the process gives rise to xerotic and ichthyotic conditions. The
      present review focusses on important biologic and molecular aspects responsible
      for normal and altered corneocyte desquamation. There is a complex relationship
      between epidermal cell production, maturation and desquamative loss. Corneocyte
      hydration, stratum corneum barrier function and enzymatic corneodesmolysis are
      involved in a dynamic interrelationship. Many physiological and environmental
      factors acting in a different time frame influence desquamation.

PMID- 10891570
TI  - Effect of helicokinins and ACE inhibitors on water balance and development of
      Heliothis virescens larvae.
AB  - The diuretic activity of the helicokinins I (YFSPWG-amide), II (VRFSPWG-amide)
      and III (KVKFSAWG-amide) was tested on Heliothis virescens larvae. All three
      kinins increased fluid secretion in isolated Malpighian tubules in a dose
      dependent manner. Injections into the haemolymph caused a significant reduction
      in weight gain after 24 h and, in the case of helicokinin I, led to an increased
      mortality of 43% within 6 days. When truncated analogues of helicokinin I were
      tested in vitro, only the pentapeptide (FSPWG-amide) stimulated fluid secretion.
      Tested in vivo the pentapeptide did not influence normal development of the
      larvae. An alanine scan of helicokinin I showed that the substitution of
      phenylalanine, tryptophan and glycine led to a massive decrease or even loss of
      diuretic activity. The substitution of the other amino acids had no effect in
      vitro. The ACE inhibitors captopril, enalapril-maleate and lisinopril were tested
      for their influence on the development of the larvae. In combination with one of
      the helicokinins the in vivo injection of the ACE inhibitors led to increased
      rates of mortality and/or reductions in pupal weight.

PMID- 10891571
TI  - Caste-specific differences in ecdysteroid titers in early larval stages of the
      bumblebee Bombus terrestris.
AB  - Mounting evidence implicates ecdysteroids in queen-worker differentiation during
      the last larval instars of highly social insects. In the present study, we
      analyzed ecdysteroid titers in queen and worker larvae of the bumblebee Bombus
      terrestris from the second to the early fourth instar. B. terrestris is of
      particular interest because caste is already determined in the second instar,
      presumably by a pheromonal signal emitted by the egg-laying queen. Caste
      differences in the adults, however, are only expressed at the physiological and
      not at the morphological level, except for the distinctly larger size of the
      queen. In the second and third instar, ecdysteroid titers in queen larvae were
      generally higher than those of workers. These early caste-specific differences,
      however, were abolished in the fourth instar. In the early fourth instar we could
      detect two small ecdysteroid peaks, with the one preceding the cocoon-spinning
      phase presenting the characteristics of a pupal commitment peak. The synchrony of
      caste differences in ecdysteroid and juvenile hormone titers suggests a
      synergistic action of these hormones in caste determination.

PMID- 10891572
TI  - Electrophysiological studies of olfaction in the whip spider Phrynus parvulus
      (Arachnida, Amblypygi).
AB  - The olfactory response of the whip spider Phrynus parvulus from Costa Rica was
      examined using a technique analogous to that used for insect electroantennograms
      on the tarsi of the antenniform legs which bear multiporous sensilla. Responses
      to 42 chemicals representing different chain lengths of alkanes, carboxylic
      acids, alcohols, aldehydes, and ketones, as well as some esters, monoterpenes,
      and phenolics were examined. Fifty-four percent of the chemicals tested elicited
      responses. Concentration-response curves were generated for guaiacol, hexanal,
      methyl salicylate, benzaldehyde, octanoic acid, and linalool. Guaiacol,
      benzaldehyde, and hexanol elicited the greatest responses and no differences were
      detected between the sexes. Compounds with chain lengths of six carbon atoms
      generated strong responses and most monocarboxylic acids and ring compounds
      elicited responses. Some compounds produced increases in potential believed to
      arise from a hyperpolarizing effect on the neurons. The broad spectrum of
      chemicals to which these animals respond is similar to results of other studies
      examining the general olfactory sense of insects. It is possible that odor
      learning plays a significant role in the behavior of amblypygids.

PMID- 10891573
TI  - Calcium transport by isolated anterior and posterior Malpighian tubules of
      Drosophila melanogaster: roles of sequestration and secretion.
AB  - Ca(2+) transport was examined in isolated Malpighian tubules (MTs) of adult
      Drosophila melanogaster. All segments of both anterior and posterior MTs have
      substantial capacity to transport Ca(2+) and to play a role, therefore, in
      calcium homeostasis and elimination of excess dietary Ca(2+). Approximately 85%
      of Ca(2+) which enters the tubule is sequestered, and approximately 15% is
      secreted in soluble form into the tubule lumen. Tubules secreting fluid at
      maximal rates can remove an amount of Ca(2+) equal to the whole animal calcium
      content in approximately 9 h. Distal segments of the pair of anterior MTs can
      sequester the same amount of Ca(2+) in <2 h. Functional advantages of high Ca(2+)
      turnover rates are discussed. Transepithelial Ca(2+) secretion is increased by
      treatments which depolarize the transepithelial potential (thapsigargin, high
      K(+)), or acidify the secreted fluids (bicarbonate-free salines). The effects of
      pharmacological reagents and variations in bathing saline ionic composition
      indicate that the processes of secretion and sequestration are controlled
      independently, and that diltiazem-sensitive Ca(2+) channels are an important
      component of sequestration. The contribution of some form of apical Ca(2+) pump
      is evaluated.

PMID- 10891574
TI  - Effects of temperature and dietary sucrose concentration on respiration in the
      silverleaf whitefly, Bemisia argentifolii.
AB  - A system consisting of a flow-through chamber connected to a commercial infrared
      gas analysis system was developed to measure homopteran respiration during
      feeding. Using this system, respiration rates of 202 and 206 umol CO(2) h(-1) g(
      1) (4.96 and 5.04 ml CO(2) h(-1) g(-1)) were determined for whiteflies and cotton
      aphids, respectively, at 25 degrees C on diets containing 15% sucrose. These
      rates were considerably higher than those of other stationary insects, indicating
      that whiteflies and aphids maintain a relatively high metabolic rate when
      feeding. Whitefly respiration increased with temperature from 25 to 46 degrees C
      with a Q(10) of about 2 on diets containing 10, 15 and 20% sucrose, but less than
      2 on diets containing 2.5 and 5% sucrose. Respiration rates were similar on the
      diets containing >10% sucrose, but were generally lower on the diets containing
      <10% sucrose. Respiration rates decreased upon extended exposure to 47 degrees C;
      the rate of decrease was inversely related to the dietary sucrose concentration
      up to 15%. The results indicate that whiteflies require a sucrose concentration
      of between 5 and 10% (i.e. 0.15 and 0.3 M) for maximum rates of metabolism while
      feeding. Higher concentrations of sucrose in the diet delayed high-temperature
      mortality, possibly a reflection of the high sucrose requirement for sorbitol
      synthesis in whiteflies.

PMID- 10891575
TI  - Eicosanoids rescue Spodoptera exigua infected with Xenorhabdus nematophilus, the
      symbiotic bacteria to the entomopathogenic nematode Steinernema carpocapsae.
AB  - Xenorhabdus nematophilus is a pathogenic bacterium causing insect haemolymph
      septicemia, which leads to host insect death. To address the fundamental
      mechanisms underlying this haemolymph septicemia, or the immunodepressive
      response of the host insects following bacterial infection, we tested a
      hypothesis that the insect immune-mediating eicosanoid pathway is blocked by
      inhibitory action of the bacterium. Haemocoelic injection of the bacteria into
      the fifth instar larvae of Spodoptera exigua reduced the total number of living
      haemocytes with postinjection time and resulted in host death in 16 h at 25
      degrees C. The lethal efficacy, described by the median lethal bacterial dose
      (LD(50)), was estimated as 33 colony-forming units per fifth instar larva of S.
      exigua. The lethal effect of the bacteria on the infected larvae decreased
      significantly with the addition of exogenous arachidonic acid (10 ug), a
      precursor of eicosanoids. In comparison, injections of dexamethasone (10 ug), a
      specific inhibitor of phospholipase A(2), and other eicosanoid biosynthesis
      inhibitors elevated significantly the bacterial pathogenicity. Live X.
      nematophilus induced the infected larvae to form less nodules than did the heat
      killed bacteria, but the addition of arachidonic acid increased the number of
      nodules formed significantly in response to live bacterial injection. The
      treatment with dexamethasone and other inhibitors, however, decreased the nodule
      formation after injection of heat-killed bacteria. These results indicate that
      eicosanoids play a role in the immune response of S. exigua, and suggest strongly
      that X. nematophilus inhibits its eicosanoid pathway, which then results in
      immunodepressive haemolymph septicemia.

PMID- 10891576
TI  - Age-specific decrease in aerobic efficiency associated with increase in oxygen
      free radical production in Drosophila melanogaster.
AB  - This study was designed to test the free radical theory of aging by using
      Drosophila melanogaster as a model system. Oxygen free radicals are generated by
      mitochondria during the process of normal oxidative metabolism. Age-specific
      measurements of oxygen consumption, heat production and anti-oxidant enzyme
      activity were obtained from two inbred lines of male flies, one selected for
      longevity and one normal-lived. The findings of this study demonstrate that
      although oxygen consumption remains relatively constant over the majority of the
      life span of each line of flies, aerobic efficiency declines with advancing age.
      This loss of aerobic efficiency manifests itself as a decline in total body
      metabolism as measured by heat production, and appears to be associated with an
      age-specific increase in damage inflicted upon mitochondria by oxygen free
      radicals.

PMID- 10891577
TI  - Insect cellular reactions to the lipopolysaccharide component of the bacterium
      Serratia marcescens are mediated by eicosanoids.
AB  - Nodulation, which begins with the formation of cellular microaggregates, is the
      predominant cellular defense reaction to bacterial infections in insects. We
      suggested that these reactions to bacterial infections are mediated by
      eicosanoids. The lipopolysaccharide (LPS) component of some bacterial cells
      stimulates defense reactions in mammals and insects. Here, we report on
      experiments designed to test the hypothesis that eicosanoids mediate
      microaggregation reactions to LPS. Injections of LPS (purified from the
      bacterium, Serratia marcescens) into larvae of the tenebrionid beetle, Zophobas
      atratus, stimulated microaggregation reactions in a dose-dependent manner.
      Treatments with eicosanoid-biosynthesis inhibitors immediately prior to LPS
      challenge sharply reduced the microaggregation responses. Separate treatments
      with specific inhibitors of phospholipase A(2), cyclooxygenase and lipoxygenase
      reduced microaggregation, supporting our view that microaggregate formation
      involves lipoxygenase and cyclooxygenase products. The inhibitory influence of
      dexamethasone was apparent within 30min after injection, and microaggregation was
      significantly reduced, relative to control insects, over the following 90min. The
      dexamethasone effects were reversed by treating LPS-injected insects with the
      eicosanoid precursor, arachidonic acid. These findings indicate that cellular
      defense reactions to a specific component of bacterial cells are mediated by
      eicosanoids, and open up new possibilities for dissecting detailed hemocytic
      actions in insect immune reactions to bacterial infections.

PMID- 10891578
TI  - Associations between female remating behavior, oogenesis and oviposition in
      Drosophila melanogaster and Drosophila pseudoobscura.
AB  - An association between female remating behavior, oogenesis and oviposition was
      examined in Drosophila melanogaster and Drosophila pseudoobscura to investigate
      mechanisms that elicit remating. Females receptive to remating oviposited more
      eggs in both species; however, the species differed in the association between
      remating behavior and the number and distribution of oocyte stages. We found no
      differences in the number of either developing eggs of different stages or mature
      eggs between female D. pseudoobscura that were either receptive or nonreceptive
      to remating. In contrast, D. melanogaster females that are receptive to remating
      had significantly more mature eggs in the ovaries than nonreceptive females.
      Nonremating females had a significantly greater number of immature, vitellogenic
      oocytes. These results suggest that factors associated with oogenesis are related
      to female remating behavior in D. melanogaster but not in D. pseudoobscura. We
      discuss these results in conjunction with other evidence on the role male
      ejaculatory components play in mediating female remating behavior.

PMID- 10891579
TI  - L-Glutamate retrieved with the moulting fluid is processed by a glutamine
      synthetase in the pupal midgut of Calpodes ethlius.
AB  - From apolysis until pupal ecdysis, the pharate pupa of the Brazilian Skipper
      (Calpodes ethlius) lies wrapped in a prepupal shell composed of the larval
      cuticle and an ecdysial space (ES) filled with enzyme-rich moulting fluid (MF).
      In the 4h before ecdysis the pharate pupa drinks the moulting fluid through its
      mouth and anus, and transfers the cuticular degradation products to its midgut
      (MG). At the same time, extra fluid passes across the body wall of the pharate
      pupa and flushes out the ES. The MF is recovered at an overall rate of 70ul/h and
      reabsorbed across the pharate pupal midgut at about 26ul/h. L-Glutamate was found
      to be the dominant amino acid in the moulting fluid. Total MF glutamate peaked at
      850nmol about 8h before pupal ecdysis (P-8), but by ecdysis it had dropped to
      nearly zero as the MF became diluted with new fluid and was consumed. The drop in
      glutamate in the ES coincided with a rise in the glutamine content of the fluid
      in the midgut lumen. The highest rate of glutamine synthesis occurred in midguts
      isolated from pharate pupae actively drinking MF (P</=-4). The enzyme glutamine
      synthetase (GS) was found to be active in glutamate metabolism in the pharate
      pupal midgut. Glutamine synthesis in the midgut was L-glutamate-dependent and
      inhibited by two selective competitive inhibitors of GS activity, L-methionine
      sulfoximine (MSO) and glufosinate ammonium (GLA). Injection of GS inhibitors into
      the prepupal ES greatly reduced the glutamine content of the midgut epithelium by
      P+24. Although a corresponding increase in midgut glutamate levels was not seen,
      midgut serine levels in treated animals rose, suggesting that GS inhibitors
      shunted the MF-derived glutamate along an alternative metabolic pathway. GLA was
      much more toxic to pupae than MSO. Midgut GS appears to play a central role in
      the recycling of L-glutamate across the pupal MG epithelium at pupation.

PMID- 10891580
TI  - Seizures and sensory stimulation result in different patterns of brain derived
      neurotrophic factor protein expression in the barrel cortex and hippocampus.
AB  - Brain-derived neurotrophic factor (BDNF) is important for the development and
      trophic support of neurons, and may be involved in controlling axonal sprouting
      and synaptic plasticity. In order to investigate the activity-dependent
      regulation of the BDNF gene, BDNF expression was examined within the rat
      somatosensory cortex (SSC) and hippocampus following vibrissae stimulation,
      kainic acid induced seizure, and pentylenetetrazol (PTZ) induced seizure. The
      specific goals of this study were to determine the time course and magnitude of
      BDNF's activity-dependent expression, and to compare the expression patterns of
      three commonly used neuronal activation paradigms. Our results demonstrate three
      novel observations. First, the patterns of BDNF protein expression are dependent
      upon the neuronal stimulation model used. Both unilateral whisker stimulation (a
      model of experience dependent plasticity) and kainic acid induced seizure were
      able to increase the levels of BDNF protein within the SSC and hippocampus. In
      contrast, PTZ induced seizure did not increase BDNF protein levels in either
      tissue. Second, there is a dissociation between BDNF mRNA and protein levels
      following PTZ induced seizure. PTZ seizures resulted in strong increases of BDNF
      mRNA levels without corresponding increases of the protein. Finally, whisker
      stimulation resulted in an unexpected increase in BDNF mRNA and protein levels
      within the hippocampus. These results suggest specific types of neuronal activity
      can regulate gene expression differently. Furthermore, temporal and spatial
      differences between the expression of BDNF protein and mRNA levels suggest that
      the BDNF gene is regulated at the level of translation as well as transcription.

PMID- 10891581
TI  - A 5' segment of the mouse Zic1 gene contains a region specific enhancer for
      dorsal hindbrain and spinal cord.
AB  - Zic1 encodes a zinc finger protein, which is required for the development of the
      dorsal neural tissue. The gene is a mammalian homologue of the Drosophila odd
      paired. We examined the regulatory elements in the 5' flanking region of the Zic1
      gene as an initial step to understanding how the Zic1 expression is restricted to
      the dorsal neural tissue. When a 2.9-kb fragment of the 5' flanking segment of
      the mouse Zic1 gene was linked to the E. coli beta-galactosidase gene, the enzyme
      was consistently expressed in the dorsal half of the embryonic spinal cord and in
      the vestibulocochlear nucleus in all four transgenic mouse lines. The transgene
      expression mimics the Zic1 expression with respect to the region where it occurs.
      But this is not so for the neuronal cell types. This suggests that the segment
      contains a region-specific enhancer. In vivo and in vitro deletion analyses
      indicated that there are essential regions between -2.0 and -0.9 kb and within
      the proximal 0.9 kb. The distal element is necessary for the transgene expression
      in the embryonic dorsal spinal cord whereas the adult vestibulocochlear nucleus
      expression is regulated by both elements. In these regions, there are sequences
      similar to the binding sequences for potential regulatory proteins.

PMID- 10891582
TI  - The subcellular localization of Otx2 is cell-type specific and developmentally
      regulated in the mouse retina.
AB  - Recent evidence implicates homeodomain-containing proteins in the specification
      of cell fates in the central nervous system. Here we report that in the embryonic
      mouse eye Otx2, a paired homeodomain transcription factor, was found in retinal
      pigment epithelial cells and a restricted subset of retinal neurons, including
      ganglion cells. In the postnatal and adult eye, however, both the cellular and
      subcellular distribution of the Otx2 protein were cell type-specific. Otx2 was
      detected only in the nuclei of retinal pigment epithelial and bipolar cells, but
      was present in the cytoplasm of rod photoreceptors. Immunohistochemical studies
      of retinal explants and transfected cell lines both suggested that the retention
      of Otx2 in the cytoplasm of immature rods is a developmentally regulated process.
      The differential distribution of Otx2 in the cytoplasm of rods and the nucleus of
      other cell types, suggests that subcellular localization of this transcription
      factor may participate cell fate determination during specific phases of retinal
      development.

PMID- 10891583
TI  - Partial cloning of constitutive and inducible nitric oxide synthases and detailed
      neuronal expression of NOS mRNA in the cerebellum and optic tectum of adult
      Atlantic salmon (Salmo salar).
AB  - Studies of different species have implicated nitric oxide (NO) synthase (NOS) in
      various physiological and pathological events. Three major NOS isoforms are
      present in the brain of mammals; endothelial NOS (eNOS), neuronal NOS (nNOS) and
      inducible NOS (iNOS). Little is known about the significance of the presence of
      these proteins in the brain. We report the first investigation into the presence
      of nNOS and iNOS isoforms in a teleost, adult Atlantic salmon (Salmo salar).
      Complementary DNA was synthesized from cerebellum and thymus mRNA using RT-PCR
      techniques with primers against conserved regions of NOS. Cloning and sequencing
      revealed a partial gene sequence of 560 bp corresponding to mammalian nNOS from
      cerebellum cDNA. The predicted protein sequence of identified salmon nNOS
      possessed 85% identity to that of mammalian nNOS. Northern blot analysis of
      different tissues revealed expression in brain and heart, and indicated
      expression of three different nNOS mRNAs in the brain. In addition, a 389 bp
      sequence corresponding to iNOS was identified in thymus cDNA. Salmon iNOS is
      almost identical to rainbow trout iNOS (95%), but shows much less amino acid
      identity to goldfish (65%) and mammalian (52%) iNOS. Phylogenetically, all
      vertebrate nNOS and iNOS homologues are clustered separately. Expression studies
      by means of in situ hybridization revealed abundant nNOS mRNA transcripts in
      distinct neuronal populations throughout the Purkinje cell layer of the corpus
      cerebellum and the periventricular layer of the optic tectum. Our data show that
      adult Atlantic salmon possess a gene encoding an nNOS isoform and putative
      alternatively spliced forms, which are expressed in distinct neuronal populations
      in the cerebellum and optic tectum, and in yet unidentified cell types in the
      heart. The data suggest that the arising of different vertebrate NOS isoforms is
      an evolutionary old event. The well conserved sequences present in salmon and
      mammalian nNOS may reflect their importance in protein function, whereas
      interspecies distributional differences in cellular expression of nNOS and
      sequence differences of iNOS may reflect variations and specializations in routes
      of NO action in the vertebrate phylogeny.

PMID- 10891584
TI  - Immunohistochemical localization of the P2Y(1) purinergic receptor in neurons and
      glial cells of the central nervous system.
AB  - This study reports the characterization of a polyclonal antiserum to a carboxy
      terminal epitope of the P2Y(1) receptor and its use in immunolocalization studies
      of this receptor in the CNS. The antibody recognized a major band of 42 kDa in
      Western blot of tissue homogenates from rat and bovine brain. Immunohistochemical
      studies confirmed early reports about the presence of the P2Y(1) receptor in the
      corpus callosum, habenula and ductal cells of the salivary gland. In addition, we
      found that the P2Y(1) receptor is intensely expressed in Purkinje cells, in deep
      layers of the cerebral cortex and in ischemic-sensitive areas of the hippocampus.
      Moreover, oligodendrocytes and astrocytes in brain white matter tracts and optic
      nerve were also immunoreactive. The intense expression of the P2Y(1) peptide in
      the aforementioned cell types suggests that this receptor may play fundamental
      roles in glial physiology. This antiserum should be a useful tool to study the
      presence of the P2Y(1) receptor in different tissues and cell cultures as well as
      in expression systems, and to distinguish the P2Y(1) from other subtypes of P2Y
      receptors.

PMID- 10891585
TI  - Progesterone increases mRNA levels of pituitary adenylate cyclase-activating
      polypeptide (PACAP) and type I PACAP receptor (PAC(1)) in the rat hypothalamus.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates pituitary
      hormone biosynthesis and secretion through its cognate receptors. PACAP also
      plays an important role in the regulation of ovarian steroid biosynthesis. If so,
      there might be a feedback regulation of hypothalamic PACAP synthesis by the
      pituitary and by ovarian steroids. In the present study, we used RNase protection
      assays to determine changes in mRNA levels of PACAP and type I PACAP receptor
      (PAC(1)) under the conditions of ovariectomy and replacement with ovarian
      steroids. Progesterone (P) alone or in combination with estradiol (E) induced
      significant increases in PACAP mRNA level in the medial basal hypothalamus (MBH)
      and PAC(1) mRNA levels in MBH and the preoptic area (POA). This finding suggests
      that feedback regulation takes place between the ovary and hypothalamic PACAP
      neurons. P is known to be a major regulatory feedback factor for hypothalamic
      luteinizing hormone-releasing hormone (LHRH) neurons, but P receptor is not
      present in these neurons. Therefore, we examined a possible involvement of PACAP
      in the feedback regulatory pathway of P to LHRH neurons. After an antisense
      PAC(1) oligodeoxynucleotide (ODN) was i.c.v.-injected into the third ventricle of
      E and P-treated rats, LHRH mRNA levels were determined. The ODN markedly
      decreased the P-induced increase in the LHRH mRNA level. Taken together, the
      present data suggest that PACAP may play a role as a mediator in the regulation
      of LHRH synthetic machinery by stimulatory feedback of P.

PMID- 10891586
TI  - Coitus-induced activation of c-fos and gonadotropin-releasing hormone in
      hypothalamic neurons in female rabbits.
AB  - Copulation induces hypothalamic release of neuropeptides and catecholamines,
      especially gonadotropin-releasing hormone (GnRH) and norepinephrine, in female
      rabbits. The forebrain distribution of GnRH cells and the cellular events
      responsible for the coitally induced GnRH surge have not been identified. We
      characterized the expression of c-fos mRNA before (0 min) and up to 60 min after
      coitus in forebrain tissues of mated and nonmated females and compared these
      findings with those in which single- and double-labeled GnRH/Fos protein cells
      were identified by immunocytochemistry (ICC). Enhanced expression of fos-mRNA
      occurred 30 min after coitus, especially in the anteroventral periventricular
      nucleus (AVPV), the encapsulated portion of the bed nucleus of the stria
      terminalis (BNSTe) and the ventrolateral hypothalamus (VLH); this increased fos
      mRNA activity remained elevated at 60 min in the AVPV and VLH, and was reflected
      by Fos protein expression 90 min postcoitus. Both ICC Fos-labeled and ICC GnRH
      labeled cells were widely distributed throughout the forebrain with postcoital
      increased double-labeling in the preoptic-septal areas, the anterior-medial
      hypothalamus and the VLH. The increased number of dual-labeled and unchanged
      number of single-labeled GnRH cells after coitus suggest some GnRH neurons were
      non-detected before coitus. Many dual-labeled neurons were adjacent to Fos
      labeled cells, suggesting enhanced interneuronal input to GnRH cells after
      coitus. Collectively, the results suggest that coitus activates hypothalamic GnRH
      neurons via several loci that include the AVPV, BNSTe and VLH. The distinct
      anatomical location of the AVPV, BNSTe and VLH further suggests that coital
      signals may reach the hypothalamus via separate neural pathways that are likely
      developed within the brainstem.

PMID- 10891587
TI  - Occurrence of a transcription factor, signal transducer and activators of
      transcription 3 (Stat3), in the postsynaptic density of the rat brain.
AB  - Distribution of a signal transducer and activators of transcription 3 (Stat3) was
      examined in the rat brain. Immunoreactivity was distributed in the neurons, as
      well as glia cells, throughout the rat brain. Western blotting of subcellular
      fractions showed distribution in the synaptic fractions (synaptosome, synaptic
      plasma membrane, and postsynaptic density, PSD). The occurrence of Stat3 in the
      synaptic site, especially in the PSD, was confirmed by immunoelectron microscopic
      examination. The PSD fraction had an activity that phosphorylated Stat3 at the
      tyrosine-705 site, which was confirmed by both Western blotting and
      immunoprecipitation. The PSD fraction also had a janus kinase 2 (Jak2)-like
      molecule, Jak2, believed to phosphorylate Stat3. These results indicate that the
      Jak2/Stat3 signaling system, a major pathway of cytokine signaling in the immune
      response system, may also play a role at the postsynaptic sites.

PMID- 10891588
TI  - Quantitative autoradiographic distribution of gamma-hydroxybutyric acid binding
      sites in human and monkey brain.
AB  - gamma-Hydroxybutyric acid (GHB), a naturally occurring metabolite of GABA, is
      present in micromolar concentrations in various areas of the mammalian brain.
      Specific GHB binding sites, uptake system, synthetic and metabolizing enzymes
      have been identified in CNS. The present study shows the anatomical distribution
      of GHB binding sites in sections of primate (squirrel monkey) and human brain by
      radioligand quantitative autoradiography. In both species the highest densities
      of binding sites were found in the hippocampus, high to moderate densities in
      cortical areas (frontal, temporal, insular, cingulate and entorhinal) and low
      densities in the striatum; no binding sites were detected in the cerebellum. High
      density of GHB binding was found in the monkey amygdala. In addition the binding
      characteristics of [(3)H]GHB to membrane preparations of human brain cortex were
      examined. Scatchard analysis and saturation curves revealed both a high (K(d1)
      92+/-4.4 nM; B(max1) 1027+/-110 fmol/mg protein) and a low-affinity binding site
      (K(d2) 916+/-42 nM; B(max2) 8770+/-159 fmol/mg protein). The present study is the
      first report on the autoradiographic distribution of specific GHB binding sites
      in the primate and human brain: such distribution is in both species in good
      agreement with the distribution found in the rat brain.

PMID- 10891589
TI  - Identification of syntaxin 1A as a novel binding protein for presenilin-1.
AB  - Mutations in the presenilin 1 gene have been shown to result in Alzheimer's
      disease. Presenilin 1 is a multi-transmembrane protein with a large hydrophilic
      loop near the C-terminus. This region is required for known functions of
      presenilin 1. We have constrained this loop within the active site of the
      bacterial protein, thioredoxin, to mimic its native conformational state. This
      hybrid protein was used as bait in a yeast two hybrid screen in an attempt to
      identify presenilin binding proteins. By this method syntaxin 1A, a synaptic
      plasma membrane protein, was identified as a novel binding protein for presenilin
      1. In vitro experiments confirm the two-hybrid results suggesting that PS1 binds
      syntaxin under physiological conditions.

PMID- 10891590
TI  - Postnatal development of orexin/hypocretin in rats.
AB  - We examined developmental changes of orexins/hypocretins and their receptors
      (OX1R and OX2R) in the rat hypothalamus from postnatal day 0 to 10 weeks, using
      in situ hybridization histochemistry for the prepro-orexin, OX1R and OX2R mRNAs
      and immunohistochemistry for orexin-A and orexin-B. The prepro-orexin mRNA was
      weakly detected in the lateral hypothalamic area (LHA) from days 0 to 15. Orexin
      A- and -B-like immunopositive cells and fibers were not detected from days 0 to
      10, but they were observed after day 15. The prepro-orexin mRNA in the LHA
      markedly increased between days 15 and 20. The OX1R mRNA was detected in the
      ventromedial hypothalamic area (VMH) at day 0. The OX2R mRNA was not detected in
      the paraventricular nucleus (PVN) at days 0 and 1, but weakly observed on day 5.
      The OX1R mRNA in the VMH and OX2R mRNA in the PVN gradually increased throughout
      the postnatal period. Next, we examined the effects of milk deprivation and
      intraperitoneal (i.p.) administration of leptin on the hypothalamic prepro-orexin
      mRNA in pups. Although 24-h milk deprivation did not affect the level of the
      prepro-orexin mRNA at days 5 and 10, i.p. administration of leptin from days 0 to
      3 caused a significant increase in the prepro-orexin mRNA on days 5 and 10. These
      results suggest that the development of orexins may be associated with
      developmental changes such as increase of leptin, weaning, feeding and
      sleep/wakefulness states.

PMID- 10891591
TI  - Experience-dependent decrease in synaptically localized Fra-1.
AB  - The Fos family of transcription factors has been repeatedly shown to participate
      in the long-term neural responses associated with a variety of physiological
      stimuli, including activity-dependent plastic processes. Quite recently, several
      transcription factors have been found in synaptic regions, localized in dendrites
      and presynaptic terminals. Here we show that the transcription factor Fos-related
      antigen-1 (Fra-1) was detected in synaptosomes (Syn) and synaptic plasma membrane
      (SPM) fractions from the rat cerebral cortex and hippocampus as a single band
      migrating with M(r) 42-43 kDa. The 55-kDa c-Fos protein was also detected in syn
      and SPM fractions. Conversely, the inducible 62-65-kDa c-Fos is present in
      nuclear fractions from metrazole-treated animals (positive control), but not in
      Syn or SPM fractions. Furthermore, no Fra-2, Fos B or c-Jun immunoreactivities
      were detected in these same synaptic regions. DNA-mobility shift assays showed
      the presence of specific AP-1 binding activity in synaptic protein extracts.
      Immunoelectronmicroscopic analysis of cortical and hippocampal tissues revealed
      that Fra-1 and Fos-like immunoreactivities are localized in association with
      presynaptic plasma membranes. One trial inhibitory avoidance training, a
      hippocampal-dependent task, is associated with a time-dependent decrease (-31%)
      in Fra-1, but not in 55-kDa c-Fos, levels in hippocampal SPM fractions. In
      hippocampal homogenates, we do not detect significant changes in Fra-1
      immunoreactivity, suggesting that this behavioural experience is probably
      accompanied by a subcellular redistribution of Fra-1 protein. These results
      suggest that Fra-1 may participate in the communication between synapse and the
      nucleus and in experience-dependent hippocampal plasticity.

PMID- 10891593
TI  - Specific downregulation of presenilin 2 gene expression is prominent during early
      stages of sporadic late-onset Alzheimer's disease.
AB  - Mutations in the presenilin genes PS1 and PS2 cause familial Alzheimer's disease
      (AD). In a previous study, we reported that PS2 mRNA levels are decreased in the
      hippocampus, frontal cortex and basal forebrain of subjects with late-onset
      sporadic AD. In this study, we examined whether this downregulation occurs as the
      disease progresses from mild to severe stages or whether downregulation of PS2
      expression is an early event in AD. We used in situ hybridization histochemistry
      to quantify the level of expression of PS2 message in the hippocampus of normal
      subjects and subjects with mild, moderate or severe AD. Several regions of the
      hippocampus which are sequentially susceptible to AD neuropathology as the
      disease progresses in severity were analyzed. We demonstrate that specific
      downregulation of PS2 expression is as severe in subjects with mild AD as it is
      in subjects in late stages of the disease. In addition, we show that hippocampal
      regions that are relatively free of AD neuropathology during early stages of the
      disease exhibit severely compromised PS2 mRNA levels even in mild AD cases. In
      contrast, PS2 is expressed at normal levels in the cerebellum, a region which
      succumbs to significantly fewer AD-related insults even at very advanced stages
      of the disease. These results suggest that the specific downregulation of PS2
      gene expression is an early event in sporadic late-onset AD.

PMID- 10891592
TI  - Induction of aquaporin-4 water channel mRNA after focal cerebral ischemia in rat.
AB  - Aquaporin-4 (AQP4) is a member of a water-selective channel aquaporin-family and
      mainly expressed in the several structures of the brain and in the collecting
      duct of the kidney. Here we show its functional involvement in the water
      homeostasis of the ischemic brain. The expression of AQP4-mRNA is increased in
      the peri-infarcted cortex during the observation period ( approximately 7 days)
      after MCA-occlusion, maximally on day 3. The change corresponds to the generation
      and resolution of brain edema monitored by MRI. The signals for the mRNA are
      predominantly observed in glial cells in the molecular and outer granular layer
      of the peri-infarcted cortex. These results indicate that AQP4 plays a role in
      post-ischemic edema formation.

PMID- 10891594
TI  - Point mutation associated with X-linked dominant Charcot-Marie-Tooth disease
      impairs the P2 promoter activity of human connexin-32 gene.
AB  - Many lines of evidence suggest that connexin-32 gap junction is involved in the
      exchange of information and metabolites in the peripheral nervous system. It has
      been shown that connexin-32 protein and mRNA are expressed in Schwann cells that
      function as myelinating cells of the peripheral nervous system. The physiological
      importance of connexin-32 gap junctions in regulating the normal function of
      myelinating Schwann cell is indicated by recent findings that X-linked dominant
      Charcot-Marie-Tooth disease, a hereditary peripheral neuropathy, is associated
      with the mutations of connexin-32 gene. Recently, we encountered a Taiwanese
      family affected with X-linked dominant Charcot-Marie-Tooth neuropathy. Therefore,
      we investigated the possible mutation in the coding and noncoding regions of the
      connexin-32 gene of affected members of this family. Our results suggest that a G
      to-A transition at the position -215 (in relation to the transcription initiation
      site) of the nerve-specific P2 promoter region is associated with the
      pathogenesis of X-linked dominant Charcot-Marie-Tooth disease. Further
      experiments using the promoter assay indicate that G-to-A mutation at the
      position -215 greatly impairs the transcriptional activity of connexin-32 P2
      promoter. These findings propose that a reduced expression of connexin-32 mRNA
      and protein in the myelin sheath could be responsible for the development of X
      linked dominant Charcot-Marie-Tooth neuropathy.

PMID- 10891595
TI  - Caloric restriction prevents age-related deficits in LTP and in NMDA receptor
      expression.
AB  - A major focus of aging research has been the search for treatments that will
      prevent or ameliorate the memory deficits associated with aging. One paradigm,
      lifelong caloric restriction, has been reported to reduce some of the effects of
      aging. In the current report, we examined the effects of this treatment on age
      related deficits in LTP, a putative cellular building block for memory formation.
      We report here that lifelong caloric restriction completely prevents the age
      related deficit in LTP. In addition, we report that there is a dramatic decrease
      in the expression of the NMDA receptor subunit NR1 in aged rats and this age
      related defect is also prevented by caloric restriction. These data provide a
      molecular and cellular mechanism by which life long caloric restriction may
      ameliorate some of the cognitive deficits associated with the aging process.

PMID- 10891596
TI  - Expression of proliferating cell nuclear antigen (PCNA) in the adult and
      developing mouse nervous system.
AB  - Proliferating cell nuclear antigen (PCNA) is essential for the function of DNA
      polymerases delta and epsilon. Because proliferating cell nuclear antigen is
      required for DNA replication and repair, PCNA is abundantly expressed in
      proliferating cells. Interestingly, PCNA mRNA has also been detected in the adult
      mouse brain by Northern blot analysis. In this study, two monoclonal antibodies
      against PCNA, PC10 and 19F4, were used for Western blot analysis. Monoclonal
      antibody PC10, but not 19F4, detected a band in the adult mouse brain extract.
      This PC10-reactive protein in the brain displayed a more acidic isoelectric point
      than PCNA by two-dimensional gel electrophoresis. In situ hybridization showed
      that PCNA mRNA was abundantly expressed in the adult mouse subventricular zone.
      Additionally, relatively low levels of PCNA mRNA expression were also found in
      neurons throughout the central nervous system, however, no hybridization was
      observed in the white matter. Immunohistochemistry was also performed using 19F4
      and PC10, and staining of progenitor cell nuclei in the subventricular zone was
      observed with both antibodies. Whereas 19F4 immunostaining was restricted to
      progenitor cells, PC10 immunostaining was also found in postmitotic
      nonproliferating cell nuclei. In the cortical neuroepithelium of developing mice,
      the distribution of PC10 immunoreactivity was wider than that of 19F4
      immunoreactivity and PCNA mRNA expression. These results suggest that
      proliferating cell nuclear antigen mRNA is expressed not only in proliferating
      cells but also in nonproliferating cells such as neurons. The protein recognized
      only with PC10 may be a modified, most probably a phosphorylated PCNA.

PMID- 10891597
TI  - Angiotensin AT(2) receptor stimulates ERK1 and ERK2 in quiescent but inhibits ERK
      in NGF-stimulated PC12W cells.
AB  - To investigate the influence of AT(2) receptor stimulation on the ERK pathway and
      elucidate potential mechanisms of angiotensin II (ANG II)-mediated neuronal
      differentiation, we analysed tyrosine phosphorylation and activity of ERK after
      ANG II treatment of both quiescent and NGF-treated PC12W cells. Tyrosine
      phosphorylation of ERK1 and ERK2 corresponded with the activity of ERK. While ANG
      II induced an initial activation of ERK in quiescent cells, the NGF-mediated
      plateau of ERK-stimulation was lowered by costimulation with ANG II. All effects
      of ANG II were sensitive to AT(2) - but not AT(1) receptor blockade. Ang II
      mediated neurite outgrowth in PC12W cells was inhibited by co-treatment with the
      MEK inhibitor PD 098059. These findings demonstrate that the AT(2) receptor
      modulates ERK activity depending on the overall cellular input. The distinct
      regulation of ERK by ANG II and NGF further indicates basic differences in AT(2)
      receptor- and NGF-induced neuronal differentiation.

PMID- 10891598
TI  - Binding specificity of monoclonal antibody AD2: influence of the phosphorylation
      state of tau.
AB  - Using recombinant human tau protein phosphorylated by a brain extract and the
      glycogen synthase kinase-3beta in the absence or the presence of heparin, we
      showed that phosphorylation-dependent antibody AD2 recognition only requires
      phosphorylated Ser-396. By the Spot multiple peptide synthesis method, we showed
      that Tyr-394, Ser(P)-396 and Pro-397 are critical for AD2 binding. A decrease in
      the binding of AD2 was observed with increasing phosphorylation of residues in
      the vicinity of Ser(P)-396.

PMID- 10891599
TI  - Serum-free induced neuronal apoptosis-like cell death is independent of caspase
      activity.
AB  - Cultured cortical neurons survived in a density-dependent manner under serum-free
      conditions. Low-density cultured cells died in an aurintricarboxylic acid (ATA)
      sensitive manner, which was accompanied with marked chromatin condensation and
      nuclear fragmentation. These features, characteristic for apoptosis, were not
      attenuated by DEVD-CHO, a caspase-3-specific inhibitor, or zVAD-FMK, a broad
      range caspase inhibitor, while zVAD-FMK showed a marked inhibition of
      camptothecin-induced cell death. Therefore, cortical neurons died in an apoptosis
      like and a caspase-independent manner under serum-free conditions.

PMID- 10891600
TI  - Fetal and adult human CNS stem cells have similar molecular characteristics and
      developmental potential.
AB  - The mammalian central nervous system (CNS) contains multipotent stem cells that
      develop into neurons, astrocytes and oligodendrocytes. Our current data show that
      fetal and adult human CNS stem cell isolates display similar proliferation
      kinetics, differentiate into three major cell types of the nervous system and
      express similar sets of regulatory genes. However, each individual CNS stem cell
      isolate could be distinguished by its specific gene expression and developmental
      potential.

PMID- 10891601
TI  - Developmental changes in the expression of NMDA receptor subunits (NR1, NR2A,
      NR2B) in the cat visual cortex and the effects of dark rearing.
AB  - The present study used Western blots to determine changes in the level of
      expression of the three major NMDA receptor subunits, NR1, NR2A, and NR2B, in
      relation to the 'critical period' in cat visual cortex. NR2A rose dramatically
      (10-fold) from very low levels at 1 week to a peak at 5 weeks and gradually
      declined into adulthood (twofold). NR2B showed a similar time course to NR2A, but
      the rise from 1 to 5 weeks was of lesser magnitude (twofold). NR1 was expressed
      at comparable levels at 1, 5, 10 weeks and declined markedly (fivefold) in older
      animals. No significant effects of dark rearing on the levels of NR2B and NR1
      were found. However, NR2A expression was significantly elevated in normal
      compared to dark reared visual cortex (twofold) at 5 weeks and significantly
      elevated in dark reared compared to normal visual cortex at 20 weeks (twofold).
      The close agreement between NR2A expression and both the time course of the
      critical period and the effects of dark rearing on that time course further
      indicates a role of this subunit in visual cortical critical period plasticity.

PMID- 10891602
TI  - Identification and cloning of a gamma 3 subunit splice variant of the human
      GABA(A) receptor.
AB  - cDNA sequences encoding two forms of the GABA(A) gamma 3 receptor subunit were
      cloned from human hippocampus. The nucleotide sequences differ by the absence
      (gamma 3S) or presence (gamma 3L) of 18 bp located in the presumed intracellular
      loop between transmembrane region (TM) III and IV. The extra 18 bp in the gamma
      3L subunit generates a consensus site for phosphorylation by protein kinase C
      (PKC). Analysis of human genomic DNA encoding the gamma 3 subunit reveals that
      the 18 bp insert is contiguous with the upstream proximal exon.

PMID- 10891603
TI  - Involvement of mu-opioid receptors in potentiation of apomorphine-induced
      climbing behavior by morphine: studies using mu-opioid receptor gene knockout
      mice.
AB  - The present study examined the hypothesis that mu-opioid receptors contribute to
      a behavioral stimulation produced by stimulation of dopamine receptors by
      comparing responses in mu-opioid receptor knockout and wild type mice.
      Apomorphine-induced climbing behavior was augmented by 65%, in wild type mice,
      but not in mu-knockout, following subcutaneous administration of morphine (15
      mg/kg). Moreover, pretreatment with either naloxone (an opioid receptor
      antagonist) or haloperidol (a mixed D(1)/D(2) receptor antagonist) eliminated the
      enhancement by morphine of climbing behavior in wild type mice. These results
      indicate that expression of mu-opioid receptors plays an important role in the
      enhancement of climbing behavior induced by the dopamine receptor agonist,
      apomorphine. Furthermore, this augmentation is mediated by interaction between
      dopamine and mu-opioid receptors.

PMID- 10891604
TI  - Molecular analysis of avian circadian clock genes.
AB  - Unlike mammals, avian circadian rhythms are regulated by a multiple oscillatory
      system consisting of the retina, the pineal and the suprachiasmatic nucleus in
      the hypothalamus. To understand avian circadian system, we have cloned Clock and
      Period homologs (qClock, qPer2 and qPer3) and characterized these genes in
      Japanese quail. Overall, qCLOCK, qPER2 and qPER3 showed approximately 79%,
      approximately 46% and approximately 33% amino acid identity to mCLOCK, mPER2,
      mPER3, respectively. Clock was mapped to quail chromosome 4 and chicken
      chromosome 4q1.6-q2.1. Per2 and Per3 genes were both localized to
      microchromosomes. qClock mRNA was expressed throughout the day, while qPer2 and
      qPer3 showed robust circadian oscillation in the eye and the pineal gland. All
      three genes were expressed in various tissues. In addition, qPer2 mRNA was
      induced by light, but neither qClock nor qPer3 was induced. These results can
      explain the molecular basis for circadian entrainment in Japanese quail and also
      provide new avenues for molecular understanding of avian circadian clock and
      photoperiodism.

PMID- 10891605
TI  - Cortical activity related to cue-invariant shape perception in humans.
AB  - We used magnetoencephalography to search spatio-temporally for cortical activity
      related to the perception of shape defined by various visual cues in humans. The
      visual stimuli were three kinds of two-dimensional figures: two had fixed shapes
      (Diamond and Cross), the other did not (Noise). These figures were defined by
      three visual cues: difference of flicker, texture or luminance between the
      foreground and the background in the random dot pattern. Using this stimulus, we
      recorded the magnetic responses from the temporo-occipital regions of nine
      healthy subjects. Additionally, we measured the reaction time for the subjects to
      detect the figure by button-pressing. A magnetic component was identified in the
      responses. The properties of the first magnetic component differed for stimulus
      condition. The peak latency of the first magnetic component was different for the
      cues (270 ms for flicker, 360 ms for texture and 250 ms for luminance), but not
      for the figures. In contrast, the peak amplitude of the first magnetic component
      was different for the figures (96-144 fT for Diamond or Cross and 52-80 fT for
      Noise), but not for the cues. The signal source of the first magnetic component
      was estimated to lie on the ventral side of the extrastriate cortex: In the
      posterior part of the inferior temporal cortex, probably in the fusiform gyrus in
      four subjects, and in the lateral part of the occipital cortex which was outside
      of the primary visual cortex (visual area 1) in one subject. The signal source
      location was different inter-individually, but almost the same within each
      subject. Reaction time was 471 ms for flicker, 569 ms for texture and 426 ms for
      luminance, but the interval between the reaction time and the peak latency was
      constant (about 200 ms) for each cue. The first magnetic component was more
      clearly recorded from the right hemisphere than from the left.We found that the
      shape defined by the different visual cues activates the same localized site in
      the lateral extrastriate cortex. This spatial convergence suggests that there is
      a restricted locus that processes the visual shape regardless of the difference
      of the visual cue. The correspondence between the peak latency and the reaction
      time suggests that the activity of the area is responsible for the perception of
      visual shape. The inter-hemispheric difference suggests a dominance of the right
      hemisphere in visual shape processing.

PMID- 10891606
TI  - Unipolar brush cell: a potential feedforward excitatory interneuron of the
      cerebellum.
AB  - Unipolar brush cells are a class of interneurons in the granular layer of the
      mammalian cerebellum that receives excitatory mossy fiber synaptic input in the
      form of a giant glutamatergic synapse. Previously, it was shown that the unipolar
      brush cell axon branches within the granular layer, giving rise to large
      terminals. Single mossy fiber stimuli evoke a prolonged burst of firing in
      unipolar brush cells, which would be distributed to postsynaptic targets within
      the granular layer. Knowledge of the ultrastructure of the unipolar brush cell
      terminals and of the cellular identity of its postsynaptic targets is required to
      understand how unipolar brush cells contribute to information processing in the
      cerebellar circuit. To investigate the unipolar brush cell axon and its targets,
      unipolar brush cells were patch-clamped in fresh parasagittal slices from rat
      cerebellar vermis with electrodes filled with Lucifer Yellow and Biocytin, and
      examined by confocal fluorescence and electron microscopy. Biocytin was localized
      with diaminobenzidine chromogen or gold-conjugated, silver-intensified avidin.
      Light microscopic examination revealed a single thin axon emanating from the
      unipolar brush cell soma that gave rise to 2-3 axon collaterals terminating in
      mossy fiber-like rosettes in the granular layer, typically within a few hundred
      microm of the soma. In some cases, axon collaterals crossed the white matter
      within the same folium before terminating in the adjacent granular layer.
      Electron microscopic examination of serial ultrathin sections revealed that
      proximal unipolar brush cell axons and axon collaterals were unmyelinated and
      devoid of synaptic contacts. However, the rosette-shaped enlargements of each
      collateral formed the central component of glomeruli where they were surrounded
      by dendrites of granule cells and/or other unipolar brush cells, with which they
      formed asymmetric synaptic contacts. A long-latency repetitive burst of
      polysynaptic activity was observed in granule cells in this cerebellar region
      following white matter stimulation. The unipolar brush cell axons, therefore,
      form a system of cortex-intrinsic mossy fibers. The results indicate that
      synaptic excitation of unipolar brush cells by mossy fibers will drive a large
      population of granule cells, and thus will contribute a powerful form of
      distributed excitation within the basic circuit of the cerebellar cortex.

PMID- 10891607
TI  - Antisense DNA against calcineurin facilitates memory in contextual fear
      conditioning by lowering the threshold for hippocampal long-term potentiation
      induction.
AB  - In the previous study, we demonstrated that the antisense oligodeoxynucleotides
      against calcineurin Aalpha and Abeta, catalytic subunits of Ca(2+)/calmodulin
      dependent protein phosphatase, produce a facilitatory effect on long-term
      potentiation induction in the hippocampal CA1 region in rats anesthetized with
      urethane. Here, we have studied how animals, in which the hippocampal long-term
      potentiation induction is enhanced by antisense oligodeoxynucleotides against
      calcineurin, perform in learning tasks that depend on hippocampal function. The
      rats received antisense oligodeoxynucleotides by bilateral ventricular
      administration via miniosmotic pumps. We tested four groups of rats, three
      infused with either antisense oligodeoxynucleotides, scramble
      oligodeoxynucleotides, or saline, and untreated rats, for two types of
      hippocampus-dependent learning, water maze and contextual fear conditioning.
      After the behavioral tests, we conducted a long-term potentiation induction test
      to determine whether long-term potentiation induction was enhanced. In contextual
      fear conditioning, rats in which long-term potentiation induction was enhanced by
      antisense oligodeoxynucleotides displayed significantly more conditioned freezing
      response than control rats. Rats with enhanced long-term potentiation induction
      showed no differences in shock sensitivity, general activity, or light-dark
      choice from control rats. In contrast with contextual fear conditioning, rats
      with enhanced long-term potentiation induction showed no difference in spatial
      learning performance on the water maze compared with control rats. These results
      demonstrate that an enhancement in long-term potentiation induction produced by
      the inhibition of calcineurin leads to an increase in memory strength in specific
      forms of hippocampus-dependent learning.

PMID- 10891608
TI  - L-type Ca(2+) channel blocker inhibits mossy fiber sprouting and cognitive
      deficits following pilocarpine seizures in immature mice.
AB  - Behavioral and cognitive deficits are one of the most frequent sequelae of
      childhood epilepsy. Accumulating evidence indicates that epilepsy induces
      aberrant development of the mossy fibers in the hippocampus, the region that is
      commonly accepted to play a key role in learning and memory. We have therefore
      proposed that such abnormal maturation of the central nervous system may cause
      the adverse prognoses following epilepsy. Based on this hypothesis, using primary
      cultures of the dentate granule cells, we showed that the L-type Ca(2+) channel
      blocker nicardipine was neuroprotective against excessive mossy fiber
      synaptogenesis induced by prolonged depolarization that was assumed to mimic
      epileptiform conditions. Therefore, we evaluated the in vivo effect of
      nicardipine on aversive sequelae following epileptiform seizures. We found
      aberrant sprouting of the mossy fibers and poor performance of spatial and
      contextual tasks in the mice that had received treatment with pilocarpine at
      their early postnatal age. Repetitive administration of nicardipine prevented the
      mossy fiber sprouting and ameliorated the cognitive deterioration, although it
      did not show anticonvulsant actions against pilocarpine seizures. In the present
      study, we proposed two in vitro and in vivo models for evaluating epilepsy
      sequelae and noticed that L-type Ca(2+) channel blocker nicardipine was effective
      in both models. L-type Ca(2+) channel blocker may be a good candidate for a
      preventive for childhood epilepsy sequelae. Likewise, these useful systems will
      disclose additional candidates in future.

PMID- 10891609
TI  - Electrophysiological characteristics of non-bursting, glutamate decarboxylase
      messenger RNA-positive neurons of the medial septum/diagonal band nuclei of
      guinea-pig and rat.
AB  - Nuclei of the medial septum/diagonal band region of the mammalian forebrain
      contain neurons that give rise to the septohippocampal pathway, which has
      separate cholinergic and GABAergic components. This pathway is known to influence
      hippocampal-dependent memory and learning processes, but the precise role of each
      component is unclear. In this study, we tested the hypothesis that fast-firing,
      non-bursting medial septum/diagonal band neurons are GABAergic. We used brain
      slice preparations from young adult guinea-pigs and rats, or from weanling rats,
      to perform current-clamp recordings from medial septum/diagonal band neurons.
      Recorded neurons were injected with biocytin for subsequent visualization with
      fluorescent avidin, and then hybridized with a 35S-labeled riboprobe for
      glutamate decarboxylase-67 messenger RNA. As a positive control, guinea-pig
      cerebellar Purkinje cells were labeled and hybridized with the riboprobe. As
      expected, labeled Purkinje cells were glutamate decarboxylase-67 messenger RNA
      positive. Slow-firing, cholinergic (choline acetyltransferase-positive) guinea
      pig medial septum/diagonal band neurons were glutamate decarboxylase-67 messenger
      RNA negative. Contrary to our hypothesis, of the guinea-pig neurons, only three
      of 11 fast-firing neurons were glutamate decarboxylase-67 positive. Of the rat
      medial septum/diagonal band neurons, three of four were positive for glutamate
      decarboxylase-67 messenger RNA. These data suggest that fast-firing, non-bursting
      neurons of the medial septum/diagonal band, as sampled by sharp-electrode
      intracellular recordings in brain slices, may be a heterogeneous group of
      neurons, some of which are GABAergic. Together with recent data demonstrating the
      presence of another GABAergic marker, parvalbumin, in fast-firing septal neurons,
      we conclude that GABAergic septohippocampal neurons include a population of fast
      firing, non-bursting neurons. The influence of these neurons on the hippocampus
      is likely to occur on a shorter time-scale and over a wider range of firing
      frequencies as compared to slowly firing cholinergic septohippocampal neurons.

PMID- 10891610
TI  - Density and pharmacology of alpha5 subunit-containing GABA(A) receptors are
      preserved in hippocampus of Alzheimer's disease patients.
AB  - The anatomical localization and pharmacology of alpha5 subunit-containing GABA
      type-A receptors in the human hippocampal formation of Alzheimer's disease
      patients were studied with an alpha5 receptor selective ligand, [3H]L-655,708 and
      compared to age-matched human controls. Autoradiographic analyses revealed a
      heterogeneous distribution of [3H]L-655,708 binding sites in CA1-CA3 areas with
      high levels in stratum oriens, stratum pyramidale and stratum radiatum
      contrasting with low levels in stratum lacunosum. The highest quantity of alpha5
      receptors was found in the molecular layer of the dentate gyrus. This pattern of
      expression was identical in both hippocampus from control and Alzheimer's disease
      subjects. Quantitative studies demonstrated that the number of [3H]L-655,708
      binding sites is well preserved in Alzheimer's disease with only a moderate
      reduction (25-30%) in the CA1 subfield and entorhinal cortex. Furthermore,
      saturation and competition experiments with [3H]L-655,708 and representative
      benzodiazepine site ligands revealed that alpha5 receptors in Alzheimer's
      hippocampus have an alpha5beta2/3gamma2 pharmacology and structure as in control
      human brain.Overall, the data reported here provide evidence for a specific
      expression and relative sparing of alpha5 subunit-containing gamma-aminobutyric
      acid type-A receptors in the hippocampus of Alzheimer's patients.

PMID- 10891611
TI  - Hypothermia differentially increases extracellular signal-regulated kinase and
      stress-activated protein kinase/c-Jun terminal kinase activation in the
      hippocampus during reperfusion after asphyxial cardiac arrest.
AB  - Mitogen-activated protein kinases are signal transduction mediators that have
      been implicated in cell survival and cell death. This study characterized the
      activation of pathways in the hippocampus during reperfusion after global
      cerebral ischemia, as well as the influence of a regimen of hypothermia that
      reduces ischemic cell death in the hippocampus. Circulatory arrest was induced in
      rats by 8 min of asphyxia. Relative levels of phosphorylated and total
      extracellular signal-regulated kinase, stress-activated protein kinase/c-Jun N
      terminal kinase and p38 mitogen-activated protein kinase were measured in the
      hippocampus after 6, 12 or 24h of reperfusion using immunoblotting. Asphyxia
      induced a progressive increase in phosphorylated extracellular signal-regulated
      kinase and stress-activated protein kinase/c-Jun N-terminal kinase, but no change
      in phosphorylated p38 mitogen-activated protein kinase. Induction of mild
      hypothermia (33 degrees C) during reperfusion increased extracellular signal
      regulated kinase phosphorylation and produced a smaller increase in stress
      activated protein kinase/c-Jun N-terminal kinase phosphorylation at 24h.
      Hypothermia did not alter extracellular signal-regulated kinase activation in
      rats not subjected to ischemia. Extracellular signal-regulated kinase activation
      was associated with an increase in phosphorylation of the mitogen-activated
      protein kinase kinase 1/2, and was inhibited by administration of the specific
      mitogen-activated protein kinase kinase 1/2 inhibitor SL327. Immunohistochemical
      staining showed an increase in active extracellular signal-regulated kinase in
      the CA1, CA2, CA3 and dentate gyrus regions of the hippocampus after ischemia and
      reperfusion. In contrast, active stress-activated protein kinase/c-Jun N-terminal
      kinase immunoreactivity was most intense in the CA3 and dentate gyrus regions.
      These data demonstrate that both extracellular signal-regulated kinase and stress
      activated protein kinase/c-Jun N-terminal kinase pathways are activated during
      the first 24h of reperfusion after global cerebral ischemia, and that hypothermia
      increases the activation of extracellular signal-regulated kinase relative to
      stress-activated protein kinase/c-Jun N-terminal kinase. Thus, an increase in
      extracellular signal-regulated kinase activation may be associated with improved
      neuronal survival after ischemic injury.

PMID- 10891612
TI  - Effects of voluntary ethanol drinking on [125I]insulin-like growth factor-I,
      [125I]insulin-like growth factor-II and [125I]insulin receptor binding in the
      mouse hippocampus and cerebellum.
AB  - Chronic exposure to ethanol can induce widespread cell loss in the brain, in some
      cases even causing dementia. Although the underlying mechanism associated with
      ethanol toxicity has not yet been established, it is suggested that one of the
      ways in which ethanol disrupts neuronal functioning/survival is by targeting the
      actions of mitogenic growth factors. Insulin-like growth factors-I and -II and
      insulin are structurally related polypeptides with potent mitogenic and metabolic
      effects on the central and peripheral nervous systems. These growth factors and
      their respective receptors are widely distributed throughout the brain, including
      the hippocampus and cerebellum. Evidence indicates that ethanol can decrease
      plasma levels of insulin-like growth factors and can also inhibit the growth
      promoting and cell survival effects of these growth factors under in vitro
      conditions. The present study was designed to determine if voluntary ethanol
      consumption over a 21-day period could alter [125I]insulin-like growth factor-I,
      [125I]insulin-like growth factor-II and [125I]insulin receptor-binding sites in
      the hippocampus and cerebellum-areas known to be severely affected following
      chronic exposure to ethanol. C57BL/6 mice were presented with either water only
      or a choice of water and a 10% v/v ethanol solution. Mice with access to the
      ethanol solution drank an average of 5.35+/-0.77 g of ethanol/kg body weight per
      day. [125I]Insulin-like growth factor-I receptor-binding sites were found to be
      significantly increased in all subfields of the hippocampal formation, but not in
      the cerebellum, of ethanol-treated mice compared to controls. [125I]Insulin-like
      growth factor-II and [125I]insulin receptor-binding sites, on the other hand, did
      not exhibit any alterations either in the hippocampus or cerebellum following
      chronic exposure to ethanol. These results, in keeping with earlier reports,
      suggest that hippocampal insulin-like growth factor-I is more sensitive to
      ethanol treatment than either insulin-like growth factor-II or insulin, and the
      observed increase in the [125I]insulin-like growth factor-I receptor levels
      possibly reflects an activity-dependent response to prevent/slow down neuronal
      degeneration and/or to regulate subtle functional alterations that follow chronic
      exposure to ethanol.

PMID- 10891613
TI  - Decreased levels of neuropeptide Y(5) receptor binding sites in two experimental
      models of epilepsy.
AB  - It has been suggested that the anticonvulsant effects of neuropeptide Y (NPY)
      could be mediated by the activation of Y(2) and/or Y(5) receptors. NPY Y(1)
      receptor levels are known to decrease and Y(2) to increase in rat models of
      epilepsy. By using an autoradiographic approach, we investigated whether epilepsy
      models (kainic acid and kindling) are also associated with changes in Y(5)
      receptors. Compared with naive controls, [125I][Leu(31), Pro(34)]PYY/BIBP3226
      insensitive (Y(5)) binding sites in the hippocampus (strata oriens and radiatum
      of CA3 and CA1) and in the neocortex (superficial layers) were unchanged in sham
      stimulated rats, but reduced by approximately 50% in kindled rats (seven days
      after the last stimulus evokes seizure), and further reduced (to approximately 
      90%) 1h after a kindled seizure. Additionally, Y(5) receptor binding sites in the
      hippocampus and in the neocortex were unchanged 6h after kainic acid injection,
      but were highly reduced at 12 and 24h. No changes in Y(5) binding levels were
      found in the dentate gyrus and the pyramidal cell layer of the hippocampus. The
      present data suggest that changes in Y(5) receptor levels occur in epilepsy
      models. These changes may play a role in seizure expression and/or in the
      maintenance of kindling hyperexcitability.

PMID- 10891614
TI  - Cannabinoid receptor messenger RNA levels decrease in a subset of neurons of the
      lateral striatum, cortex and hippocampus of transgenic Huntington's disease mice.
AB  - One of the earliest changes, at the molecular level, that occurs in human
      Huntington's disease patients is reduction in cannabinoid receptor ligand binding
      in the substantia nigra pars reticulata compared to neurologically normal
      controls. The loss of cannabinoid receptor binding is thought to occur early in
      or prior to the development of Huntington's disease neuropathology. We wish to
      determine whether cannabinoid receptor messenger RNA levels were altered in a
      mouse model of Huntington's disease. Transgenic mice hemizygous for the promoter
      sequence and exon 1 of the human Huntington's disease gene exhibit a progressive
      neurological phenotype with many of the features of Huntington's disease. This
      neurological phenotype develops in the absence of neural degeneration making
      these mice a model system to dissociate changes related to cell dysfunction from
      changes related to cell loss. We examine the steady-state levels and cellular
      distribution of the brain-specific cannabinoid receptor messenger RNA by northern
      blot and in situ hybridization. The cannabinoid receptor messenger RNA was
      expressed throughout the striatum, cortex and hippocampus of wild-type mice. At
      four and five weeks of age, there was no difference in the distribution of the
      cannabinoid receptor messenger RNA between the wild-type and transgenic
      Huntington's disease mice. At six, seven, eight and 10 weeks of age, however, the
      Huntington's disease mice exhibit reduced levels of cannabinoid receptor
      messenger RNA in the lateral striatum compared to age-matched controls. The
      Huntington's disease mice also showed a loss of cannabinoid receptor messenger
      RNA within a subset of neurons in the cortex and hippocampus. We did not observe
      any difference in the expression of cannabinoid receptor between the wild-type
      and Huntington's disease mice throughout Ammon's horn of the hippocampus or in
      the medial striatum. The decrease in cannabinoid receptor messenger RNA levels
      preceded the development of the Huntington's disease phenotype and neuronal
      degeneration and, therefore, these transgenic mice model early cellular changes
      observed in human patients. Our results demonstrate that the single copy
      cannabinoid receptor gene is subjected to cell-specific and time-dependent
      regulation of the steady-state level of its gene product as a result of the
      expression of the Huntington's disease gene. As the endogenous cannabinoid
      receptor agonist, anandimide, has been shown to modulate dopamine
      neurotransmission within the basal ganglia, the loss of cannabinoid receptors may
      contribute to the development of motor symptoms or cognitive decline or both seen
      in Huntington's disease patients.

PMID- 10891615
TI  - Electrophysiology and pharmacology of projections from the suprachiasmatic
      nucleus to the ventromedial preoptic area in rat.
AB  - Extracellular and whole-cell patch-clamp recordings were made from neurons in the
      ventromedial preoptic area in rat horizontal brain slices. Responses to single
      pulse electrical stimulation of the ipsilateral suprachiasmatic nucleus were
      characterized using peristimulus time histograms or postsynaptic current
      recordings, and bath application of neurotransmitter receptor antagonists.
      Extracellular recordings showed that suprachiasmatic nucleus stimulation (50-150
      microA) elicited a short-latency suppression in 35 of 64 neurons (55%), with the
      majority (29/35, 83%) showing a biphasic response consisting of a short-latency
      suppression followed by a long-duration activation. In addition, 14 cells (22%)
      showed activation only, while 15 (23%) were unresponsive. The GABA(A) receptor
      antagonist bicuculline (5-10 microM) reversibly blocked suppressions evoked by
      suprachiasmatic nucleus stimulation (20/20 cells). In the majority of these
      neurons (13/20), bicuculline also unmasked an activation in response to
      stimulation. Activations elicited by suprachiasmatic nucleus stimulation, either
      in the presence or absence of bicuculline, were blocked by the non-N-methyl-D
      aspartate and N-methyl-D-aspartate glutamate receptor antagonists 6,7
      dinitroquinoxaline-2,3-dione and (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1
      phosphonic acid (10/10 cells). 6,7-Dinitroquinoxaline-2,3-dione (10 microM)
      selectively and reversibly blocked the initial, short-duration (<50 ms)
      activation, but had no effect on the longer-duration activation. In contrast, (+/
      )-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (10 microM) appeared to
      inhibit the long-duration activation selectively without affecting the initial
      rapid activation. Combined applications of the two ionotropic glutamate receptor
      antagonists blocked stimulation-induced activations completely. All the
      pharmacological effects were concentration dependent. Whole-cell patch-clamp
      recordings showed that suprachiasmatic nucleus stimulation elicited inhibitory
      postsynaptic currents or a combination of inhibitory and excitatory postsynaptic
      currents in 25 of 33 neurons tested. The inhibitory postsynaptic currents had
      short onset latencies (4.9+/-0.3 ms) and a reversal potential of -56.0+/-3.8 mV
      (n=5), and were reversibly blocked by bicuculline (5-10 microM, 4/4 cells). In
      the presence of bicuculline (5-10 microM), excitatory postsynaptic currents had
      short onset latencies (4.7+/-0.5 ms), and had a fast and a slow component. (+/-)
      3-(2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid blocked the slow, but not
      the fast, component, whereas 6,7-dinitroquinoxaline-2, 3-dione blocked the fast,
      but not the slow, component (n=7). These results suggest that the projection from
      the suprachiasmatic nucleus conveys both inhibitory (GABA) and excitatory
      (glutamate) inputs to the ventromedial preoptic area. GABA(A) receptor and both
      non-N-methyl-D-aspartate and N-methyl-D-aspartate glutamate receptors mediate
      these influences. These inputs may be responsible for conveying information
      related to circadian phase from the suprachiasmatic nucleus to regions of the
      preoptic area known to be involved in regulation of sleep/waking and other
      physiological functions.

PMID- 10891616
TI  - Phasic inhibition of dopamine uptake in nucleus accumbens induced by intravenous
      cocaine in freely behaving rats.
AB  - A new approach combining fast-scan cyclic voltammetry with iontophoretic dopamine
      delivery was used in freely behaving rats to evaluate the time-course of dopamine
      uptake inhibition in nucleus accumbens induced by intravenous cocaine at a dose
      (1.0mg/kg) known to maintain self-administration behavior. Cocaine significantly
      increased the decay time of the dopamine response without altering its magnitude
      or time to peak. An increase in decay time was evident at 2 min, peaked at 6 min
      (+87%), and decreased to baseline at 18 min after a single cocaine injection. The
      change in decay time was similar in all rats and remained essentially the same,
      albeit slightly larger, for subsequent cocaine injections both within a session
      and over repeated sessions. The change in dopamine decay time did not correlate
      with cocaine-induced motor activation, which was maximal during the first minute
      after injection and decreased slowly over the next 20 min. Our data provide
      direct evidence for a phasic change in dopamine uptake induced by intravenous
      cocaine under behaviorally relevant conditions. The relatively slow and gradual
      development of dopamine uptake inhibition, which peaks at times when behaving
      rats self-inject cocaine, is inconsistent with the suggested role of this
      mechanism in the acute rewarding (euphoric) effects of self-injected cocaine, but
      supports its role in the activational and motivational aspects of drug-seeking
      and drug-taking behavior. Because intravenous cocaine enters the brain rapidly
      and peaks in neural tissue (1-2 min) long before it effectively inhibits dopamine
      uptake (6 min), it appears that some of the acute psychoemotional ("rush"),
      behavioral, autonomic, and neuronal effects of this drug, which are apparently
      resistant to dopamine receptor blockade, are mediated via rapid central or
      peripheral mechanisms independent of monoamine uptake.

PMID- 10891617
TI  - Newly synthesized dopamine in the nucleus accumbens is regulated by beta
      adrenergic, but not alpha-adrenergic, receptors.
AB  - Previous microdialysis studies have led to the hypothesis that activation of
      mesolimbic alpha-adrenoceptors inhibits the release of mesolimbic dopamine from
      alpha-methyl-p-tyrosine-resistant, reserpine-sensitive pools, and that activation
      of mesolimbic beta-adrenoceptors stimulates the release of mesolimbic dopamine
      from alpha-methyl-p-tyrosine-sensitive, reserpine-resistant pools. In the present
      study we analysed the ability of mesolimbic alpha- and beta-adrenoceptors to
      modulate the release of dopamine from alpha-methyl-p-tyrosine-sensitive pools in
      the nucleus accumbens of high and low responders to novelty. Under non-challenged
      conditions, alpha-methyl-p-tyrosine (10(-4)M, 40 min) produced a decrease in
      dopamine release that did not differ between high and low responders to novelty.
      The continuous infusion of 10(-6)M isoproterenol (beta-adrenoceptor agonist)
      diminished the alpha-methyl-p-tyrosine-induced decrease in dopamine, whereas the
      continuous infusion of 10(-5)M phenylephrine (alpha-adrenoceptor agonist)
      remained ineffective. It is concluded that the release of mesolimbic dopamine
      from alpha-methyl-p-tyrosine-sensitive, reserpine-resistant pools is under
      excitatory control of beta-adrenergic, but not alpha-adrenergic, receptors in
      both high and low responders to novelty. In general, this study implies that
      mesolimbic dopamine that is derived from different pools is regulated via
      different noradrenergic receptors.

PMID- 10891619
TI  - Neuroanatomical targets of anxiogenic drugs in the hindbrain as revealed by Fos
      immunocytochemistry.
AB  - It is speculated that specific hindbrain transmitter pathways centred on the
      periaqueductal gray and locus coeruleus are an important integrative neural
      substrate for the expression of anxiety and the somatic symptoms and
      cardiovascular changes that accompany severe anxiety states, such as in panic
      disorder. Here we investigated the effects of various drugs, known to induce
      panic in humans and to be anxiogenic in animals, on Fos expression in the
      periaqueductal gray, locus coeruleus and other parts of the rat hindbrain. The
      drugs tested were the benozodiazepine inverse agonist FG-7142, the alpha(2)
      adrenoceptor antagonist yohimbine, the non-selective 5-hydroxytryptamine(2C)
      receptor agonist m-chlorophenyl piperazine, the adenosine antagonist caffeine and
      the cholecystokinin analogue BOC-CCK(4). A clear-cut finding was that
      administration of each anxiogenic drug caused a striking region-specific pattern
      of Fos expression within the hindbrain. In particular, the drugs commonly
      increased Fos-like immunoreactivity in the periaqueductal gray and locus
      coeruleus. Increased Fos expression in the periaqueductal gray was specific to
      the rostral dorsolateral and caudal ventrolateral regions. All the anxiogenic
      drugs also increased Fos-like immunoreactivity in the lateral parabrachial
      nucleus and nucleus of the solitary tract and all but one (BOC-CCK(4)) increased
      Fos in the dorsal raphe nucleus. Rats habituated to the test environment and
      injected with saline vehicle displayed little or no Fos-like immunoreactivity in
      the hindbrain areas investigated. In summary, each of the anxiogenic drugs tested
      (FG-7142, yohimbine, m-chlorophenyl piperazine, caffeine and BOC-CCK(4))
      increased Fos expression in a restricted number of hindbrain regions, including
      the periaqueductal gray and locus coeruleus. Previous Fos studies have found that
      these same regions are activated by various fearful environmental stimuli.
      Therefore, a specific set of hindbrain circuits may be commonly involved in the
      processing of anxiety-related information evoked by pharmacological and
      environmental manipulation. The present findings also raise the possibility that
      measurement of the effect of anxiogenic drugs on Fos expression might be a useful
      way to model hindbrain pathways activated by anxiety and possibly panic.

PMID- 10891618
TI  - Co-stimulation of D(1)/D(5) and D(2) dopamine receptors leads to an increase in c
      fos messenger RNA in cholinergic interneurons and a redistribution of c-fos
      messenger RNA in striatal projection neurons.
AB  - The anatomical subdivision of striatum in patch and matrix compartments plays an
      important role for the processing of neurotransmission through the basal ganglia
      in primates and rodents. Here we report that co-administration of D(1)/D(5) and
      D(2) receptor agonists, which induces a heterogenous and patchy pattern of c-fos
      messenger RNA expression in striatum, stimulates c-fos messenger RNA expression
      in cholinergic interneurons. Moreover, this treatment induces c-fos messenger RNA
      in projection neurons containing D(1)-, rather than D(2)-receptor messenger RNA.
      The preferential induction of c-fos messenger RNA in patches does not depend upon
      a higher degree of co-localization between D(1) and D(2) receptors in this area,
      since double in situ hybridization experiments showed a large segregation of D(1)
      and D(2) receptor messenger RNAs in the patch as well as the matrix compartments.
      By contrast, treatment with a full D(1)/D(5) receptor agonist up-regulates
      striatal c-fos messenger RNA homogenously and in similar proportions of D(1) and
      D(2) receptor messenger RNA-containing projection neurons in both medial and
      lateral striatum, but has only minor effects on c-fos messenger RNA expression in
      cholinergic interneurons. These results provide a neuroanatomical/neurochemical
      correlate to the well-known behavioral interaction between dopamine D(1)/D(5)
      agonists and dopamine D(2) agonists. They also suggest that there may be a
      relation between a heterogenous, patch-enriched c-fos messenger RNA expression
      and an increased expression of this immediate early gene in cholinergic
      interneurons.

PMID- 10891620
TI  - Neuropeptide Y-Y1 receptor antisense oligodeoxynucleotide increases the infarct
      volume after middle cerebral artery occlusion in rats.
AB  - An antisense oligodeoxynucleotide selective for the rat neuropeptide Y1 receptor
      gene was given into the left lateral ventricle in the experimental group of rats,
      whereas a missense oligodeoxynucleotide or saline was given in the control
      groups. Some rats were decapitated at 1-2h after the last injection of the
      oligodeoxynucleotides to examine their effects on the Y1 receptor density in the
      insular cortex. When compared to the Y1 and Y2 binding density of the untreated
      rats, the antisense-treated rats had reduced Y1 binding in the insular cortex but
      the Y2 binding was unaffected; treatment with missense oligodeoxynucleotide had
      no effect. Other rats underwent a right-sided middle cerebral artery occlusion at
      1-2h after the last injection of the oligodeoxynucleotides or saline to examine
      the effect on the infarction volume at three days following stroke. The antisense
      treatment resulted in a doubling of the mean infarction volume when compared to
      the missense or saline treatment.Thus, reducing the Y1 receptor density prior to
      middle cerebral artery occlusion is harmful. Neuropeptide Y may mediate
      neuroprotection against focal ischemia via the cortical Y1 receptor, since the
      immunoreactivity for neuropeptide Y has been shown to increase within the peri
      infarct cortex after middle cerebral artery occlusion.

PMID- 10891621
TI  - Caudal midline medulla mediates behaviourally-coupled but not baroreceptor
      mediated vasodepression.
AB  - Within the caudal medulla there are two regions whose activation leads to
      vasodepression and bradycardia, the caudal ventrolateral medulla and a discrete
      region of the caudal midline medulla. This study investigated, in the halothane
      anaesthetized rat, the contribution of these two vasodepressor regions to
      "homeostatic" and "behaviourally-coupled" cardiovascular regulation. In an
      initial set of experiments the contribution of each of these two regions to the
      hypotension and bradycardia evoked by acute hypovolaemia (15% haemorrhage) was
      investigated. It was found that inactivation of the caudal midline medulla
      significantly attenuated (cobalt chloride) or completely blunted (lignocaine) the
      hypotension and bradycardia evoked by acute hypovolaemia. In contrast,
      inactivation of the caudal ventrolateral medulla using cobalt chloride, although
      attenuating the magnitude of the hypotension and completely blocking the
      bradycardia, did not delay the onset of the hypotension evoked by acute
      hypovolaemia. The caudal ventrolateral medulla is known to be critical in
      homeostatic cardiovascular control through the expression of the "baroreceptor
      reflex" and the hypotension and bradycardia evoked by activation of
      cardiopulmonary afferents. In a second series of experiments we found
      inactivation of the caudal midline medulla played no role in baroreflex-evoked
      bradycardia (i.v. phenylephrine) or the hypotension and bradycardia evoked by
      cardiopulmonary afferent activation (i.v. 5-hydroxytryptamine). These data
      suggest that the caudal midline medulla and caudal ventrolateral medulla play
      different roles in cardiovascular control. The caudal ventrolateral medulla is
      involved in mediating cardiovascular changes associated with a variety of stimuli
      including "homeostatic" and "behaviourally-coupled" cardiovascular changes,
      whereas the caudal midline medulla is critical for mediating "behaviourally
      coupled" changes in arterial pressure and heart rate.

PMID- 10891622
TI  - Mechano-insensitive nociceptors encode pain evoked by tonic pressure to human
      skin.
AB  - Single unmyelinated axons in the superficial branch of the peroneal nerve of
      human subjects were recorded (microneurography) and the response patterns during
      tonic pressure stimulation (14N at 30 mm(2); 120 s) were assessed using the
      previously described "marking technique". It was found that tonic pressure
      stimuli induced augmenting pain responses which were matched by the discharges of
      initially mechano-insensitive ("silent") C-units, whereas mechano- and heat
      responsive "polymodal" C-nociceptors showed a response pattern incompatible with
      the stimulus-induced perceptions, namely strong initial excitation, followed by
      adaptation. Eighteen mechano- and heat-responsive "polymodal" C-fibers and 11
      mechano-insensitive units were studied. The former had von Frey thresholds <160
      mN, the latter were not excited by a von Frey filament of 750 mN (six of them
      responded to radiant heat stimulation). However, in the course of pressure
      stimulation, nine of the 11 mechano-insensitive units were activated after more
      than 20s. A second, identical pressure stimulus induced a stronger response in
      mechano-insensitive and a weaker response in mechano-responsive units. The
      stronger response, indicating sensitization, matched the more intense pain
      perception during the second pressure stimulus. It is concluded that mechano
      insensitive C-nociceptors encode pressure-induced pain in human hairy skin and
      that they play an important role in static mechanical hyperalgesia.

PMID- 10891623
TI  - Time-dependent changes in neurokinin(3) receptors and tachykinins during adjuvant
      induced peripheral inflammation in the rat.
AB  - Although considerable evidence exists that spinal neurokinin(1) receptors are
      involved in central sensitization of nociception, recent evidence from knockout
      studies indicates that other neurokinin receptors in the spinal cord may mediate
      a portion of the hyperalgesia caused by substance P and neurokinin A. The present
      study determined whether the second most abundant class of neurokinin receptors,
      neurokinin(3) receptors, are regulated during persistent peripheral inflammation.
      Inflammation in the hind paw of the rat was induced by intraplantar injection of
      complete Freund's adjuvant. Receptor autoradiography revealed specific binding of
      [125I]-MePhe(7)-NKB, a selective ligand for neurokinin(3) receptors, in the
      superficial dorsal horn of the spinal cord. Specific binding of [125I]-MePhe(7)
      NKB in the medial dorsal horn was reduced bilaterally two days after unilateral
      injection of complete Freund's adjuvant. Binding returned to basal levels four
      days after injection of complete Freund's adjuvant. Neurokinin(3) receptor
      messenger RNA levels doubled in the dorsal spinal cord at 12h and remained
      elevated for at least four days. The change in neurokinin(3) receptor binding and
      messenger RNA during adjuvant-induced inflammation may be a consequence of
      activation of the receptor. Spinal levels of potential endogenous ligands for
      spinal neurokinin(3) receptors were measured by radioimmunohistochemistry.
      Immunoreactive substance P but not neurokinin B peptide 2, a marker for
      neurokinin B, was reduced bilaterally during adjuvant-induced
      inflammation.Collectively, these data indicate that spinal neurokinin(3)
      receptors may play a role in spinal neurotransmission of injured rats and require
      consideration of other tachykinins as physiologically relevant ligands to spinal
      neurokinin(3) receptors.

PMID- 10891624
TI  - Genetic studies of substance abuse.
AB  - Genetic studies of substance abuse indicate that variation in the risk for the
      disorder in the population is contributed by differences in both individual
      genotypes and environment. Recent developments in genetics raise the possibility
      of disentangling the complex system of genotype-environment interaction that
      determines the development of the individual behavioral phenotype. This paper
      reviews the concepts, methods and results pertaining to genetic investigation of
      substance abuse.

PMID- 10891625
TI  - Factors influencing alcohol and illicit drug use amongst medical students.
AB  - Alcohol, illicit drug use, and other lifestyle variables, as well as stress,
      anxiety and personality were evaluated in 194 first year medical students. 45% of
      the students reported drinking above the recommended UK limits for alcohol
      consumption. The age at which the first full drink of alcohol was taken was
      predictive of the current level of alcohol use. Cannabis was the most frequently
      used illicit drug (45%). There were significant positive associations between
      alcohol consumption and experiences such as missing study, becoming more sexually
      involved and getting into a physical fight or argument. There were also
      significant positive associations between the personality characteristic of
      psychoticism and alcohol and illicit drug consumption. The effectiveness of
      current health education on alcohol and illicit drugs is questioned.

PMID- 10891626
TI  - One-year outcome of adolescent females referred for conduct disorder and
      substance abuse/dependence.
AB  - We investigated whether substance abuse/dependence, conduct disorder, and other
      psychiatric disorders improved in adolescent females who were referred to
      outpatient treatment and which variables were related to 1-year outcome. Forty
      six out of 60 conduct-disordered (CD) adolescent females with substance abuse or
      dependence were re-evaluated approximately 1 year after discharge. Treatment
      length averaged 16 weeks. Significant improvements were seen in three areas: (1)
      criminality and CD; (2) attention deficit hyperactivity disorder (ADHD); and (3)
      educational and vocational status. However, neither substance involvement nor
      depression improved, regardless of length of stay in treatment, and these females
      demonstrated significant risky sexual behaviors. In contrast to our previous work
      with adolescent males (Crowley, T.J., Mikulich, S.K., Macdonald, M., Young, S.E.,
      Zerbe, G.O., 1998. Substance-dependent, conduct-disordered adolescent males:
      severity of diagnosis predicts 2-year outcome. Drug Alcohol Depend. 49, 225-237),
      we were not able to identify pre-intake variables, other than performance IQ,
      that were related to substance use and conduct outcomes. Only two post-treatment
      factors (peer problems and number of ADHD symptoms at follow-up) were found to be
      related to CD and substance use disorders outcomes. The overall lack of pre- and
      post-treatment predictors presents interesting challenges for future research on
      adolescent females with these disorders.

PMID- 10891627
TI  - Comparative neurobiological effects of ibogaine and MK-801 in rats.
AB  - Ibogaine is a plant-derived alkaloid with putative 'anti-addictive' properties.
      Although ibogaine binds to multiple targets in the brain, recent evidence
      suggests the drug acts as an N-methyl-D-aspartate (NMDA) antagonist similar to MK
      801. The purpose of the present study was to compare neurochemical and
      neuroendocrine effects of ibogaine and MK-801 in vivo. Male rats received either
      i.p. saline, ibogaine (10 and 100 mg/kg), or MK-801 (0.1 and 1 mg/kg). Groups of
      rats (N=6-8/group) were decapitated 30 or 60 min after injection. Brains were
      harvested for analysis of dopamine (DA) and its metabolites, while trunk blood
      was collected for analysis of plasma corticosterone and prolactin. Ibogaine
      produced marked dose-dependent reductions in tissue DA with concurrent increases
      in the metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid
      (HVA). This profile of ibogaine-induced effects on DA metabolism was consistently
      observed in the cortex, striatum, olfactory tubercle, and hypothalamus. MK-801,
      on the other hand, did not reduce DA levels in any brain region but did cause
      modest region-specific elevations in DA metabolites. Ibogaine and MK-801 caused
      comparable elevations in circulating corticosterone, but only ibogaine increased
      prolactin. The present findings show that the effects of ibogaine on DA
      neurotransmission and neuroendocrine secretion are not fully mimicked by MK-801.
      Thus, the wide spectrum of in vivo actions of ibogaine can probably not be
      explained simply on the basis of antagonism at NMDA receptors.

PMID- 10891628
TI  - Significant interaction between clozapine and cocaine in cocaine addicts.
AB  - Because clozapine may be prescribed to cocaine abusing patients with
      schizophrenia, we studied cocaine-clozapine interactions in a controlled setting.
      Eight male cocaine addicts underwent four oral challenges with ascending doses of
      clozapine (12.5, 25 and 50 mg) and placebo followed 2 h later by a 2-mg/kg dose
      of intranasal cocaine. Subjective and physiological responses, and serum cocaine
      levels were measured over a total 4-h period. Clozapine pretreatment increased
      cocaine levels during the study and significantly increased the peak serum
      cocaine levels in a dose dependent manner. In spite of this elevation in blood
      levels, clozapine pretreatment had a significant diminishing effect upon
      subjective responses to cocaine, including 'expected high', 'high' and 'rush',
      notably at the 50 mg dose. There was also a significant effect upon 'sleepiness',
      'paranoia' and 'nervous'. Clozapine caused a significant near-syncopal episode in
      one subject in the study, requiring his removal from the study. Clozapine had no
      significant effect on baseline pulse rate and systolic blood pressure, but it
      attenuated the significant pressor effects of the single dose of intranasal
      cocaine. These data suggested a possible therapeutic role for clozapine in the
      treatment of cocaine addiction in humans, but also suggests caution due to the
      near-syncopal event and the increase in serum cocaine levels.

PMID- 10891629
TI  - Gender differences in acculturation and aggression as predictors of drug use in
      minorities.
AB  - High acculturation and aggression may signal increased risk of drug use among
      different ethnic groups. Drug use histories were compared with the degree of
      acculturation in 18 African-Americans and ten Hispanics. Aggressive responding
      was measured using The Point Subtraction Aggression Paradigm (PSAP) developed by
      Cherek, D.R., 1981, Psychopharmacology, 75, 339-345. Males were more acculturated
      and used more drugs than females. In PSAP responding, each gender responded more
      aggressively towards the ethnic group in which they identified with the most.
      Ethnic Identification and gender were associated with increased drug use.
      Acculturation and drug studies must consider the importance of gender within and
      across ethnic sub-populations.

PMID- 10891630
TI  - Inter-rater reliability of the SCID alcohol and substance use disorders section
      among adolescents.
AB  - Diagnostic interviews for substance use disorders tend to have high reliability
      among adults. We examined the inter-rater reliability of the substance use
      disorders section of the Structured Clinical Interview for the DSM, using 46 male
      and 25 female adolescent drinkers recruited from community and treatment sources.
      Inter-rater reliability was high for individual DSM-IV alcohol symptoms
      (kappa=0.84-1.0) and diagnoses (kappa=0.94), and for other substance use disorder
      diagnoses (kappa=0.82-1.0).

PMID- 10891631
TI  - Generalizability of project MATCH: a comparison of clients enrolled to those not
      enrolled in the study at one aftercare site.
AB  - Project MATCH is a national, randomized clinical trial of alcoholism treatment
      matching. The generalizability of Project MATCH has been questioned, as well as
      efficacy trials in general. This study investigates at one site whether there
      were differences between clients who participated in MATCH and others not entered
      into the study. Significant differences were found on three inclusion/exclusion
      related variables: plans to move, available transportation, and locator
      provision. Significant but rather small differences were also found on age and
      education. There were no significant differences on a large number of demographic
      and problem severity measures. In addition, the Alcohol Use Disorders
      Identification Test scores suggest that those included in the MATCH sample
      actually had more serious alcohol involvement than those who were ineligible or
      declined participation. Overall, the differences found do not appear to threaten
      the generalizability of the study.

PMID- 10891632
TI  - Naltrexone and lofexidine combination treatment compared with conventional
      lofexidine treatment for in-patient opiate detoxification.
AB  - This study compares a naltrexone/lofexidine combination treatment with a 7-day
      course of lofexidine alone in the treatment of opiate withdrawal in 22 opiate
      dependent patients. Withdrawal symptoms were significantly less severe on days 4
      7, and 9-13, in the naltrexone/lofexidine combination group. There were no
      significant differences in the percentage of patients completing detoxification
      or in the mean length of stay for the two groups. Both treatments had similar,
      minimal effects on blood pressure. The naltrexone/lofexidine combination was
      associated with a more rapid resolution of the opiate withdrawal syndrome than a
      7-day lofexidine-only treatment schedule, without substantial increases in
      withdrawal symptoms or hypotensive side-effects.

PMID- 10891633
TI  - Validation of the Christo Inventory for Substance-misuse Services (CISS): a
      simple outcome evaluation tool.
AB  - The Christo Inventory for Substance-misuse Services (CISS) was developed as a
      single page outcome evaluation tool completed by drug/alcohol service workers
      either from direct client interviews or from personal experience of their client
      supplemented by existing assessment notes. Its 0-20 unidimensional scale consists
      of 10 items reflecting clients' problems with social functioning, general health,
      sexual/injecting risk behaviour, psychological functioning, occupation, criminal
      involvement, drug/alcohol use, ongoing support, compliance, and working
      relationships. Comparison scores indicating low, average or high problem severity
      were produced by 243 drug users attending a harm minimisation out patient service
      and 102 alcohol users at an outpatient alcohol service. Means and cut-off scores
      for abstinence oriented treatments were derived from a 6-month follow-up of 90
      treated drug users. Sub sets of the harm minimisation sample were used to derive
      item alpha, test-retest and inter-rater reliability coefficients of 0.74, 0.82
      and 0.82, respectively. The inter-rater coefficient increased to 0.91 when
      retests were conducted the same day. Among the abstinence oriented treatment
      sample the CISS produced correlations ranging from 0.43 to 0.99 with the Opiate
      Treatment Index and measures of trait anxiety, unpleasant life events, poor
      quality of life and low self-esteem. The simplicity, flexibility and brevity of
      the CISS make it a useful tool allowing comparison of clients within and between
      many different service settings.

PMID- 10891634
TI  - Alcohol consumption amongst South African farm workers: a challenge for post
      apartheid health sector transformation.
AB  - A cross-sectional analytical study was conducted amongst farm workers in the
      deciduous fruit industry in South Africa to assess levels of alcohol consumption
      and abuse, and to explore the impact of the DOP system, whereby farm workers are
      paid in part with alcohol, on indicators of alcohol consumption. High levels of
      alcohol consumption were found. On the CAGE and a shortened version of the MAST
      questionnaires, 87 and 65%, respectively, had responses indicating problem
      drinking. Close to half of the sample consumed more grams of alcohol per week
      than considered safe drinking (210 g) and 9.3% consumed amounts in excess of
      dangerous drinking (>490 g/week). Almost one-fifth (19.4%) of workers interviewed
      reported current use of the DOP system, and 47.8% of workers had experience of
      one or more farms in the past where the DOP system had been used. Workers with
      past experience of the DOP system were 9.8 times less likely to be asbstainers
      than colleagues without exposure to the DOP system. The pervasive effects of
      excessive alcohol consumption, and its relationship to past and current DOP
      practices pose substantial public health challenges to the transformation of
      health services currently underway in South Africa.

PMID- 10891635
TI  - The spectrum of neuropsychiatric abnormalities associated with electrical status
      epilepticus in sleep.
AB  - Electrical status epilepticus in sleep (ESES) is an electrographic pattern
      consisting of an almost continuous presence of spike-wave discharges in slow wave
      sleep. ESES is frequently encountered in pediatric syndromes associated with
      epilepsy or cognitive and language dysfunction. It can be present in various
      evolutionary stages of a spectrum of diseases, the prototypes of which are the
      'continuous spikes and waves during slow wave sleep' syndrome (CSWS), the Landau
      Kleffner syndrome (LKS), as well as in patients initially presenting as benign
      childhood epilepsy with centrotemporal spikes (BECTS). The purpose of this
      article is to review the literature data on the semiology, electrographic
      findings, prognosis, therapeutic options, as well as the current theories on the
      pathophysiology of these disorders. The frequent overlap of CSWS, LKS, and BECTS
      urges an increased level of awareness for the occasional transition from benign
      conditions such as BECTS to more devastating syndromes such as LKS and CSWS.
      Identification of atypical signs and symptoms, such as high discharge rates,
      prolonged duration of ESES, neuropsychiatric and cognitive dysfunction, lack of
      responsiveness to medications, and pre-existing neurologic conditions is of
      paramount importance in order to initiate the appropriate diagnostic measures.
      Prolonged and if needed repetitive sleep electroencephalographs (EEGs) are
      warranted for proper diagnosis.

PMID- 10891636
TI  - Benign partial epilepsies in infancy.
AB  - Benign partial epilepsies are not rare in infancy and comprise two forms,
      although both are closely related. One is partial epilepsy with complex partial
      seizures (CPS) and the other one with secondarily generalized seizures (SGS). The
      most frequent site of seizure origin was in the temporal area in the former and
      central, parietal or occipital area in the latter. The former has not been well
      recognized because of subtle seizure manifestations and a favorable outcome. Its
      unique characteristics should be emphasized because it may be difficult to
      diagnose it unless we know its presence. Benign convulsions are also common in
      infancy. Most of them may belong to partial epilepsy with SGS, although
      confirmation with ictal EEG recording is necessary for accurate diagnosis. Some
      are familial and many of them seem to show an autosomal dominant pattern, but
      some seem to have autosomal recessive inheritance.

PMID- 10891637
TI  - Infantile convulsions with mild gastroenteritis.
AB  - The development of sensitive new molecular genetic techniques has led to the
      detection of rotavirus in cerebrospinal fluid, stools and throat swabs from
      patients with gastroenteritis with accompanying clinical symptoms similar to
      infantile benign convulsions. Small round structured virus (SRSV) has also been
      found in stools of patients with similar clinical symptoms by a new procedure.
      However, the mechanism by which these viral infections induce benign convulsions
      remains to be elucidated. The present paper reviews recent virological and
      clinical studies of seizures probably caused by gastroenteritis viruses including
      rotavirus, SRSV and other viruses.

PMID- 10891638
TI  - Central nervous system complications in human herpesvirus-6 infection.
AB  - Human herpesvirus-6 (HHV-6) is the causative agent of the common childhood
      infectious disease, exanthem subitum. After the virus was recently isolated from
      humans, it was found to be closely related to human cytomegalovirus (CMV), and
      was thus classified within the beta subgroup of human herpesviruses. HHV-6
      possesses neurotropism in vitro, and it has been suggested that primary infection
      can cause complications of the central nervous system (CNS), including febrile
      seizures and encephalitis/encephalopathy. There is also speculation that the
      direct invasion of the virus into the CNS may play an important role in causing
      these neurological complications. Moreover, there are several reports which have
      suggested an association between HHV-6 and a variety of neurological disorders in
      adults. This paper will briefly review our virological understanding of the
      virus, and summarize recent findings regarding HHV-6 as an etiologic agent for
      CNS infection.

PMID- 10891639
TI  - Repetitive intermittent hypoxia-ischemia and brain damage in neonatal rats.
AB  - OBJECTIVE: To know the effect of brief-repetitive intermittent hypoxia-ischemia
      on the development of perinatal brain damage. STUDY DESIGN: Seven-day-old Wistar
      rats underwent ligation of the unilateral common carotid artery. The animals were
      allocated to three groups (n=12 in each group) and exposed to 8% oxygen as
      follows: group A: continuous exposure for 180 min; group B: continuous exposure
      for 90 min; and group C: 10 min of exposure repeated at 10-min intervals over a
      period of 180 min (total exposure time, 90 min). Seventy-two hours after exposure
      to hypoxia, the cerebral cortex was examined to assess the degree of neuronal
      necrosis and brain damage was classified into four grades of severity, 0-3. To
      evaluate the extent of brain damage, we used immunohistochemical staining with
      TIB-128 antibody, which reacts to MAC-1 antigen specific to microglia, and
      observed the glial reaction in the cerebral cortex, hippocampus, thalamus, and
      striatum. RESULTS: All the brain damage observed in groups A-C occurred on the
      side where the ligation was performed. The most severe damage was found in group
      A animals, of which seven showed significant neuronal necrosis, having a grade 2
      or more advanced lesion. In group B, neuronal necrosis was modest, with only one
      animal having a grade 2 lesion. In group C, a significant neuronal necrosis was
      found in six animals despite having the same period of hypoxic exposure as those
      in group B. MAC-1 positive cells appeared in the cerebral cortex of
      histologically damaged animals and extended to the hippocampus, thalamus, and
      striatum in severely damaged animals from groups A, B, and C. CONCLUSION:
      Examination of the neonatal rat model suggested that repetitive and intermittent,
      rather than continuous hypoxia-ischemia, causes pronounced damage in the immature
      brain.

PMID- 10891640
TI  - Gene expression related to cholesterol metabolism in mouse brain during
      development.
AB  - Although a large amount of cholesterol is known to be needed for brain maturation
      and differentiation, cholesterol metabolism during these periods remains unclear.
      To elucidate the developmental regulation of cholesterol metabolism in the brain,
      we investigated the expression of 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA)
      reductase (EC 1.1.1.34), low-density-lipoprotein (LDL) receptor and very-low
      density-lipoprotein (VLDL)/apolipoprotein E (apo E) receptor (VLDL receptor)
      using RNase protection assay (RPA) to quantitate mRNA levels in mouse brain,
      liver and kidney during development. Messenger RNA levels of HMG-CoA reductase in
      the brain decreased with age, and those levels at -5 (5 days before birth) and 5
      days after birth were significantly higher than the control level of adult mice.
      The period from -5 to 5 days might correspond to stages of active biogenesis of
      the membranes of brain cells. The mRNA level of HMG-CoA reductase in the liver
      was also high at -5 days; a finding that correlated with cell proliferation. On
      the other hand, mRNA levels of the LDL and VLDL receptors in the brain did not
      change markedly during development. These results suggest that de novo
      cholesterol biosynthesis in brain cells plays a major role in the supply of
      cholesterol to the developing brain, rather than the uptake of cholesterol from
      serum lipoproteins through lipoprotein receptors.

PMID- 10891641
TI  - Otoacoustic emission in patients with neurological disorders who have auditory
      brainstem response abnormality.
AB  - Otoacoustic emissions (OAEs) were evaluated in 51 ears of 30 patients with a
      severe auditory brainstem response (ABR) waveform abnormality. Thirteen ears
      showed no ABR to click sound of higher intensity than 100 dBSPL (group 1).
      Fourteen ears exhibited only wave V or a decreased amplitude pattern of ABR
      (group 2). Twenty-four ears showed a predominant wave I or no wave III pattern
      (group 3). Almost all the ears with absent ABR showed no OAE, which strongly
      suggested hearing loss of cochlear origin, although one patient with alternating
      hemiplegia of childhood exhibited definite OAEs and auditory reactions without
      ABR. One patient with mitochondrial myopathy, encephalopathy, lactic acidosis,
      and strokelike episodes (MELAS) and her mother in group 2 had OAE abnormalities,
      which also suggested mild to severe hearing impairment. When OAEs are present, an
      accompanying ABR abnormality may be produced by brainstem dysfunction of the
      underlying disorder such as Pelizaeus-Merzbacher disease. There was a significant
      relationship (chi-square test P<0.001) between the positivity of the distortion
      product OAE response and the clinical auditory reactions in 24 patients, although
      their ABR abnormalities did not reflect hearing impairment directly. Careful
      examination of both audiometry and OAEs might be necessary for further assessment
      of the hearing function in pediatric patients with neurological disorders and
      specific auditory nerve disease.

PMID- 10891642
TI  - Focal polymicrogyria in mother and son.
AB  - This 9-year-old boy was admitted at the age of 2 with a diagnosis of congenital
      hemiparesis while the rest of physical and neurological examination was normal.
      His score in the Wechsler intelligence scale was 80. Right fronto-parietal
      cortical dysplasia with hemisphere atrophy was evident by computerized tomography
      scanning and magnetic resonance imaging. The latter, also disclosed abnormal
      thick cortex which was interpreted as polymicrogyria or pachygyria. Karyotype was
      normal. He had a hemifacial motor seizure at the age of 7. At the age of 8
      frequent atonic or inhibitory seizures were presented. Asymmetric bilateral spike
      discharges with high voltage in the right hemisphere during the EEG recording
      were found. His mother, a 35-year-old woman (Full scale; Adult intelligence
      scale: 85) also had congenital hemiparesis. She never had seizures and her EEG
      was normal. Magnetic resonance imaging disclosed right fronto-parietal cortical
      dysplasia with ipsilateral hemisphere atrophy. Karyotype was normal. Our cases
      should be interpreted as a familial presentation of the anomaly, probably with
      autosomal-dominant transmission.

PMID- 10891644
TI  - Hormones, brain, and neuropsychopharmacology

PMID- 10891643
TI  - Neonatal intracranial teratoma.
AB  - Brain tumors diagnosed in neonatal period are extremely rare. A case of neonatal
      intracranial teratoma with extracranial extension, presenting with upper airway
      obstruction is reported. The preoperative diagnosis was made by cranial computed
      tomography and magnetic resonance imaging.

PMID- 10891645
TI  - Effect of ethanol on BOLD response to acoustic stimulation: implications for
      neuropharmacological fMRI.
AB  - The effects of ethanol on acoustically stimulated blood oxygenation level
      dependent (BOLD) signal response in healthy humans was examined with echo planar
      functional magnetic resonance imaging (fMRI). An acquisition mode minimizing
      neuronal activation by scanner noise in combination with acoustic excitation by a
      pulsed 1000-Hz sine tone was used. Paradigms were repeated three times before and
      after the ingestion of 0.7 g of ethanol/kg(body weight). Linear correlation
      analyses (r>/=0.40) revealed bilateral BOLD responses in the auditory cortex.
      Significant voxels covered a cortical volume of approximately 3 ml that was
      reduced by approximately 40% after ethanol. The BOLD signal change initially
      reaching approximately 3% was reduced by 12-27%, depending on the definition of
      the region of interest for signal quantitation. Because ethanol produces
      vasodilation, the hemodynamic contribution to the BOLD signal change was
      estimated by modeling the relationship between regional cerebral blood flow
      (rCBF) and BOLD signal changes. Assuming a baseline flow increase by 10% after
      ethanol intake, the resulting 'Flow-BOLD-Dependence' (FBD) curve suggested that
      the ethanol-related BOLD signal reduction was approximately 7-12% greater than
      the reduction contributed purely by vasodilation. However, simultaneous
      determination of rCBF and regional cerebral blood volume would be required for an
      exact quantitation of the neuronally induced BOLD response. Although the FBD
      model needs empirical validation, its cautious implementation appears to be
      helpful if fMRI is used in combination with vasoactive drugs.

PMID- 10891646
TI  - A voxel-based investigation of regional cerebral blood flow abnormalities in
      obsessive-compulsive disorder using single photon emission computed tomography
      (SPECT).
AB  - Several functional imaging studies have reported abnormalities of the
      orbitofrontal and anterior cingulate cortices, striatum and thalamus in obsessive
      compulsive disorder (OCD). These studies have often been limited by small patient
      samples and image analysis methods that rely on region-of-interest (ROI)
      approaches. We have assessed resting regional cerebral blood flow with 99mTc-ECD
      SPECT in 26 unmedicated OCD patients and 22 healthy control subjects using the
      voxel-based Statistical Parametric Mapping method for data analysis. We found a
      significantly reduced ECD uptake in OCD patients relative to the control subjects
      in the right lateral orbitofrontal cortex, and in the left dorsal anterior
      cingulate cortex (P<0.001 two-tailed, uncorrected for multiple comparisons).
      There were significant positive correlations in the OCD group between the ECD
      uptake in the left lateral orbitofrontal cortex and ratings for obsessive
      compulsive symptoms (OCS), and between the ECD uptake in the right medial
      orbitofrontal cortex and the ratings for both OCS and depressive symptoms. There
      were also unpredicted significant ECD uptake increases in the cerebellum in OCD
      patients, as well as a negative correlation between posterior cingulate ECD
      uptake and OCS severity (P<0.05, corrected for multiple testing). These results
      implicate specific subregions of the orbitofrontal and anterior cingulate
      cortices in the pathophysiology of OCD, as well as suggesting the involvement of
      other areas not usually included in ROI-based imaging studies. With the
      incorporation of voxel-based methods and the use of large patient samples, rCBF
      SPECT studies may continue to provide valuable information about the functional
      anatomy of OCD.

PMID- 10891647
TI  - Regional cerebral blood flow during exposure to food in obese binge eating women.
AB  - Cerebral responses elicited by the sight of food were evaluated in eight obese
      binge eating, 11 obese and 12 normal-weight non-binge eating women. Regional
      cerebral blood flow (rCBF) was mapped while the subjects were looking at a
      picture of a landscape (control) or at a portion of food (food exposure), and was
      measured by [99mTc]ethyl-cysteine-dimer and single photon emission computed
      tomography. Exposure to food was associated with different changes in the
      cerebral blood flow (normalized to mean cerebellar counts) of the right and left
      hemispheres in the obese binge eating than in the obese or normal-weight non
      binge eating women. As compared with the non-binge eating groups, the obese binge
      eating women had, due to food exposure, a greater increase in the cerebral blood
      flow in the left than right hemisphere, especially in the frontal and pre-frontal
      regions. In addition, strong linear correlations were observed in this group
      between the rCBF of the left frontal and pre-frontal regions and the increase in
      the feeling of hunger during the exposure to food. Left hemisphere and its
      frontal and pre-frontal regions could thus play a role in binge eating behavior
      in humans.

PMID- 10891648
TI  - Functional anatomical study of psychogenic amnesia.
AB  - Psychogenic amnesia is characterized by an inability to recall information
      already stored in the patient's memory. It is usually related to a stressful or
      traumatic event that cannot be explained by manifest brain damage. To examine the
      underlying functional disturbance of brain areas in this condition, we performed
      a positron emission tomography (PET) activation study on a psychogenic amnesic
      patient and on 12 normal control subjects. A task requiring explicit retrograde
      memory of faces was compared with a control task. To assess functional
      modifications associated with the processes of recovery, a second PET study was
      performed on the patient 12 months after onset. During the task, activation of
      the right anterior medial temporal region including the amygdala was increased in
      the psychogenic amnesic patient. Activation of the bilateral hippocampal regions
      increased only in the control subjects. During recovery, the right anterior
      medial temporal region became less active while the right hippocampal region
      became more active. Activation levels also differed in the anterior cingulate
      cortex, prefrontal cortex and some other cortical regions between control
      subjects and the patient. These findings suggest that the changes in these limbic
      and limbic-cortical functions are related to symptoms of the psychogenic amnesia.

PMID- 10891649
TI  - Detection of Chlamydia species-specific serum antibodies by prior adsorption of
      common genus-specific antibodies.
AB  - To establish a method for the detection of Chlamydia species-specific antibodies
      to the three species of Chlamydia responsible for human disease, the author
      attempted to remove Chlamydia genus-specific antibodies by prior adsorption with
      heterologous Chlamydia antigen. The effects of adsorption with heterologous
      antigen were investigated by the microplate immunofluorescence antibody
      technique. The Chlamydia genus-specific antibodies in immune animal sera were
      significantly reduced by prior adsorption with heterologous Chlamydia antigen.
      Chlamydia pecorum which does not infect humans was found to be useful for the
      adsorption. A preliminary test using Chlamydia trachomatis-infected human sera
      showed that this adsorption method with C. pecorum is applicable to the
      serodiagnosis of human Chlamydia infections.

PMID- 10891650
TI  - Immunobiological activities of a chemically synthesized lipid A of Porphyromonas
      gingivalis.
AB  - A synthetic lipid A of Porphyromonas gingivalis strain 381 (compound PG-381),
      which is similar to its natural lipid A, demonstrated no or very low endotoxic
      activities as compared to Escherichia coli-type synthetic lipid A (compound 506).
      On the other hand, compound PG-381 had stronger hemagglutinating activities on
      rabbit erythrocytes than compound 506. Compound PG-381 also induced mitogenic
      responses in spleen cells from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ
      mice, as well as LPS-responsive C3H/HeN mice. The addition of polymyxin B
      resulted in the inhibition of mitogenic activities, however, compound 506 did not
      show these capacities. Additionally, compound PG-381 showed a lower level of
      activity in inducing cytokine production in peritoneal macrophages and gingival
      fibroblasts from C3H/HeN mice, but not C3H/HeJ mice, in comparison to compound
      506. Thus, this study demonstrates that the chemical synthesis of lipid A,
      mimicking the natural lipid A portion of LPS from P. gingivalis, confirms its low
      endotoxic potency and immunobiological activity.

PMID- 10891651
TI  - Enhanced resistance to experimental systemic candidiasis in tilorone-treated
      mice.
AB  - Candida albicans is an increasingly important opportunistic fungal pathogen in
      immunocompromised patients. Natural killer (NK) cells constitute an important
      immune effector mechanism and are involved in the response to different
      pathological disorders. We wished to determine if this immune mechanism is
      involved in the specific response to C. albicans. Tilorone hydrochloride and
      related compounds have been described to display antiviral and antitumoral
      activity, as well as to enhance NK cell activity. In this study, we show the
      antimicrobial activity of different tilorone analogues and the enhanced
      resistance of tilorone-treated mice in experimental systemic candidiasis. We also
      present data suggesting that there is a correlation between NK cell activation
      and the resistance to experimental systemic candidiasis. Thus, it seems that the
      immunosurveillance of metastatic spread and the infection by C. albicans share
      some immune effector mechanisms, in particular activation of NK cells.

PMID- 10891652
TI  - Specific antibody promotes opsonization and PMN-mediated killing of phagocytosis
      resistant Enterococcus faecium.
AB  - Many clinical isolates of Enterococcus faecium are resistant to neutrophil (PMN)
      mediated phagocytosis and killing in the presence of normal human serum. We have
      now examined the ability of specific polyclonal rabbit antibodies to promote
      opsonization and killing of phagocytosis-resistant E. faecium. Immune rabbit
      serum generated against formalin-killed E. faecium TX0016, a phagocytosis
      resistant strain, markedly promoted binding of TX0016 organisms to PMNs and PMN
      mediated killing. These effects were dramatically reduced by (a) adsorption of
      immune serum with E. faecium TX0016, but not by adsorption with a strain of E.
      faecium susceptible to phagocytosis, and (b) incubation of immune serum with
      carbohydrate purified from TX0016, but not by incubation with a surface protein
      extract from TX0016. IgG purified from immune serum was unable by itself to
      promote bacterial binding to PMNs. However, specific IgG was able to promote
      binding to PMNs and PMN-mediated killing in the presence of normal human serum as
      a complement source, as were F(ab')(2) and Fab fragments produced from it, and
      the alternative pathway of complement was sufficient to promote IgG- and
      F(ab')(2)-mediated opsonization. PMN complement receptor type 3, but not
      complement receptor type 1, was involved in bacterial binding to PMNs induced by
      the combination of F(ab')(2) fragments and normal human serum. These results
      suggest that opsonization by antibodies potentially directed against bacterial
      carbohydrate, in conjunction with complement activation, has an important role in
      the host defense against phagocytosis-resistant E. faecium.

PMID- 10891653
TI  - Prevention of endothelial cell cytokine induction by a Staphylococcus aureus
      lipoprotein.
AB  - Staphylococcal strain 8325-4, unlike other staphylococcal strains, fails to
      induce cytokine IL-1 and IL-6 gene expression in human endothelial cells. In the
      present investigation, this strain was shown to release a product that inhibited
      cytokine gene expression in endothelial cells infected with another
      staphylococcal strain. This inhibition was due to prevention of internalization,
      but not adherence, of bacteria by endothelial cells. Induction of endothelial
      cell cytokine gene expression by lipopolysaccharide was not affected by the
      staphylococcal supernatant. In contrast to endothelial cells, 8325-4 did not
      inhibit Wb-induced cytokine gene expression in monocytes. Further
      characterization of the inhibitory factor suggests that it is a lipoprotein and
      that both protein and lipid components play a role in its inhibitory function.

PMID- 10891654
TI  - Sensitivity of the Burkholderia cepacia complex and Pseudomonas aeruginosa to
      transducing bacteriophages.
AB  - Burkholderia cepacia is now recognised as a life-threatening pathogen among
      several groups of immunocompromised patients. In this context, the proposed large
      scale use of these bacteria in agriculture has increased the need for a better
      understanding of the genetics of the species forming the B. cepacia complex.
      Until now, little information has been available on the bacteriophages of the B.
      cepacia complex. Transducing phages, named NS1 and NS2, were derived from the
      lysogenic B. cepacia strains ATCC 29424 and ATCC 17616. The frequency of
      transduction per phage particle ranged from 1.0x10(-8) to 7.0x10(-6) depending on
      the phage and recipient strain used. The host range of NS1 and NS2 differed but
      in each case included environmental and clinical isolates, and strains belonging
      to several species and genomovars of the B. cepacia complex. The host range of
      both phages also included Pseudomonas aeruginosa. Some B. cepacia complex
      isolates were sensitive to the well-characterised P. aeruginosa transducing
      phages, B3, F116L and G101. The lytic activity of NS1 and NS2 was inhibited by B.
      cepacia lipopolysaccharide suggesting that this moiety is a binding site for both
      phages. The molecular size of the NS1 and NS2 genomes was approximately 48 kb.

PMID- 10891655
TI  - Rattus norvegicus: not a model for Aeromonas-associated gastroenteritis in man.
AB  - The lack of a suitable animal model of Aeromonas-associated diarrhoea has
      hampered investigations into Aeromonas pathogenic mechanisms. Hence, a published
      report that clindamycin-pretreated rats developed signs and symptoms of enteritis
      following intragastric inoculation of an Aeromonas strain required further
      investigation. Although we could demonstrate long-term colonisation (>12 days)
      and histological damage in this animal model with Pseudomonas aeruginosa isolated
      from patients with chronic diarrhoea, this was not seen with Aeromonas spp. Six
      Aeromonas strains, selected for their potential virulence and colonising
      abilities and including the strain from the original report, were either not
      recovered from stools or were recovered for no longer than 2 days post
      inoculation. Intestinal histology remained normal. Destruction of bacteria in
      vivo appeared to be due to immune mechanisms as inoculum strains were not
      'suicidal' or unduly sensitive to low pH or clindamycin. This study was,
      therefore, unable to validate the clindamycin-treated rat model as a useful one
      for investigating the enteropathogenicity of Aeromonas species. Possible reasons
      for the discrepancy between our study and the original report are discussed.

PMID- 10891656
TI  - Bactericidal antibody response to Neisseria meningitidis serogroup B in patients
      with bacterial meningitis: effect of immunization with an outer membrane protein
      vaccine.
AB  - We evaluated the bactericidal antibody response to Neisseria meningitidis
      serogroup B in convalescent patients (n=65) from bacterial meningitis. Patients
      infected with B meningococci were stratified according to their vaccination
      status (Cuban BC vaccine) into group 1 (immunized) (n=12) and group 2 (non
      immunized) (n=15). The results suggested that antibody titers > or =2 (log(2))
      indicate a specific immune response to N. meningitidis. In group 1, 64% of
      patients had a significant antibody titer (> or =2) in their acute sera against a
      B:4:P1.15 strain, compared to only 21% of group 2 patients. All patients from
      group 1 without bactericidal antibodies in their acute sera had a significant
      increase (at least 2-fold increase in log(2) titers) in antibody titers in their
      convalescent sera, in contrast, to only 27% of patients from group 2 (P=0.06).
      Using mutant strains lacking OMP1 or OMP5, it was shown that OMP1 was an
      important antigen recognized by immunized patients but not by non-immunized
      patients.

PMID- 10891657
TI  - Identification and characterisation of a novel conserved outer membrane protein
      from Neisseria meningitidis.
AB  - We have identified a homologue of the adhesin AIDA-I of Escherichia coli in
      Neisseria meningitidis. This gene was designated nhhA (Neisseria hia homologue),
      as analysis of the complete coding sequence revealed that it is more closely
      related to the adhesins Hia and Hsf of Haemophilus influenzae. The sequence of
      nhhA was determined from 10 strains, and found to be highly conserved. Studies of
      the localisation by Western immunoblot analysis of total cell proteins and outer
      membrane complex preparations and by immunogold electron microscopy revealed that
      NhhA is located in the outer membrane. A strain survey showed that nhhA is
      present in 85/85 strains of N. meningitidis representative of all the major
      disease-associated serogroups, based on Southern blot analysis. It is expressed
      in the majority of strains tested by Western immunoblot.

PMID- 10891658
TI  - Roles of endogenous cytokines in liver apoptosis of mice in lethal Listeria
      monocytogenes infection.
AB  - Various bacterial pathogens have been identified as mediators of apoptosis.
      Apoptosis reportedly shows both detrimental and beneficial effects on biological
      functions. We studied the role of liver apoptosis in lethal Listeria
      monocytogenes infection and the regulation of apoptosis by endogenous cytokines
      during infection. Apoptosis was observed in the spleen but not in the liver of
      infected mice, whereas the induction of liver necrosis was evident by rising
      levels of serum aminotransferases in these animals. Apoptosis was detected in the
      liver of L. monocytogenes-infected mice which had been treated with monoclonal
      antibody (mAb) against tumor necrosis factor-alpha (TNF-alpha) or interleukin-6
      (IL-6), or in TNF-alpha(-/-) mice, but not in gamma- interferon (IFN-gamma)(-/-)
      mice or mice which had been treated with mAb against IL-4 or IL-10. Augmentation
      of liver apoptosis in mice treated with mAb against TNF-alpha or IL-6 or in TNF
      alpha(-/-) mice correlated with the increase in bacterial numbers in the organ,
      while no augmentation of apoptosis was observed in the liver of IFN-gamma(-/-)
      mice irrespective of the marked increase in bacterial numbers in the organs,
      indicating that augmentation of liver apoptosis may not be merely due to the
      increase in bacterial growth in the organs. These results suggest that TNF-alpha
      and IL-6 may play an important role in protecting the liver from apoptosis in
      lethal L. monocytogenes infection.

PMID- 10891659
TI  - Sensitivity of bacterial coaggregation to chelating agents.
AB  - Coaggregation between pairs of microorganisms was found to be inhibited by
      chelating agents, such as acetylacetone, citrate, EDTA and
      carboxymethylcellulose. Assays were conducted on eight pairs of
      periodontopathogens and one pair consisting of Escherichia coli and Saccharomyces
      cerevisiae. The inhibitory effects of the chelating agents were reversible except
      for Actinomyces naeslundii 12104, the adhesin of which was irreversibly
      inactivated. Even though the bacteria possessed different kinds of adhesins,
      their sensitivity to chelating agents appears to be a common property. Non-toxic
      chelating agents, such as carboxymethylcellulose and citrate, may prove to be
      useful anti-adhesins.

PMID- 10891660
TI  - [Hormone replacement therapy and increased risk of breast cancer. Opinion of the
      French Association for the Study of Menopause].

PMID- 10891661
TI  - [Radiation-induced thyroid cancers].
AB  - Human epithelial thyroid radiation-induced tumorigenesis is the most frequent
      radiation-induced tumorigenic process in man. Results of different studies,
      concerning the molecular mecanism(s) of epithelial thyroid radiation-associated
      tumorigenesis show : 1) that there is not a significant difference in the
      frequency of activation of ras, gsp and trk proto-oncogenes between radiation
      associated and <<spontaneous >> thyroid tumors; 2) the relevant role played by
      RET/PTC ret proto-oncogene activating rearrangements, in the development of
      radiation-associated thyroid tumors originated after therapeutic radiation
      (mainly PTC 1) or the atomic accident of Chernobyl (mainly PTC 3) and 3) suggest
      that the patients who develop thyroid tumors after a history of irradiation, show
      a genomic instability consisting in a DNA repair defect.

PMID- 10891662
TI  - [Suppressive hormone therapy for thyroid nodules. Prospective evaluation.
      Preliminary results].
AB  - The benefit of thyroid hormone for patients with thyroid nodule is still
      controversial. Suppressive therapy is not useful to distinguish benign or
      malignant tumors, since some malignant nodules become smaller and most benign
      nodules do not shrink with thyroid hormone therapy. A prospective evaluation was
      conducted by the french Groupe de Recherche sur la Thyroide on 123 patients with
      solitary nodules : ultrasonographic volume of the nodules regressed from 2.76 to
      2.39 ml with suppressive doses of levothyroxine for 18 months, while a
      progression from 3.6 to 4.1 ml was seen for patients with placebo. The benefit of
      the suppressive therapy was also obvious on the micronodular dystrophy detected
      by ultrasonography. No side effects were seen in treated patients. These
      preliminary results argue for the benefit of suppressive therapy, as suggested by
      meta-analysis of the published randomized trials.

PMID- 10891663
TI  - [Microsomal triglyceride transfer protein and abetalipoproteinemia].
AB  - Microsomal triglyceride transfer protein (MTP) is a dimeric protein complex
      consisting of protein disulfide isomerase and a unique 97 kDa subunit. In vitro,
      MTP accelerates the transport of triglyceride, cholesteryl ester, and
      phospholipid between vesicles. It was recently demonstrated that
      abetalipoproteinemia, a disease characterized as an inability to produce
      chylomicrons and very low density lipoproteins in the intestine and liver,
      respectively, is the result of a genetic absence of MTP. Downstream effects
      resulting from this defect, include very low plasma cholesterol and triglyceride
      levels, absence of plasma apolipoprotein B and a lipid malabsorption syndrome,
      leading to lipo-soluble vitamin deficiencies. A low fat diet is instituted to
      eliminate the diarrhea. In addition, a therapy with vitamins A and E is essential
      to prevent patients from developing secondary effects such as neuropathy, muscle
      weakness, and retinopathy.

PMID- 10891664
TI  - [Chromatin remodeling in estrogen-dependent and independent human breast cancer
      cell lines].
AB  - Chromatin restricts the accessibility of DNA to regulatory factors; its
      remodeling over the regulatory regions contributes to the control of gene
      expression. An increasing number of evidence links defects in chromatin
      remodeling machinery and cancer. Our aim is to elucidate the role of chromatin
      structure in the control of the expression of hormone-induced genes in breast
      cell lines estrogen-dependent or -independent for growth. Mammary tumor growth is
      controlled by steroid hormones via their nuclear receptor and by growth factors
      via tyrosine kinase receptors. 50 % of these tumors elude to hormonal control.
      This limits the anti-estrogen therapy. As a model, we have analyzed in several
      cell lines the chromatin organization of the regulatory regions of two genes, pS2
      that is associated with a good prognostic, and cathepsin D (catD) that is a bad
      prognostic marker. The expression of the two genes is estrogen-regulated in
      estrogen-dependent cell line MCF7. In contrast in the hormone-independent cell
      line MDA MB 231, pS2 is not expressed and catD is constitutively expressed.
      Within the regulatory regions of pS2 gene, we have localized two regions that
      undergo a hormone-dependent change in chromatin structure in MCF7 cells but not
      in MDA MB 231. The lack of chromatin remodeling in MDA MB 231 cells is not due to
      the absence of expression of the estrogen receptor in the cell line. The
      expression of pS2 gene can be correlated with chromatin remodeling over the
      regulatory regions of pS2 gene. In contrast catD regulatory regions did not
      display hormone-dependent changes in chromatin structure, suggesting that hormone
      regulation takes place within regions with a constitutively open chromatin
      structure.

PMID- 10891665
TI  - [Ovarian endometriosis cyst with iodine 131 uptake : first case of false positive
      in the follow up for differentiated thyroid carcinoma].
AB  - A whole body scan is performed after a radioiodine treatment in patients with
      differentiated thyroid carcinoma. This scan is useful coupled with thyroglobulin
      level for the patient's management. When unusual uptake is found, investigations
      have to be done to eliminate thyroid metastasis. A 28-year old woman underwent a
      total thyroidectomy for micro papillary carcinoma. Two years and a half after,
      ultrasonography of the neck showed a small lymph node in homolateral side of
      carcinoma. It was decided to begin treatment with iodine 131. The post
      therapeutic scan showed an abnormal pelvic uptake. IRM found no osseous
      abnormality but an ovarian lesion. After surgery, histological diagnosis was an
      endometriosis cyst without thyroid or tumoral cells. Abdominal ou pelvic iodine
      false positive are rare. Ovarian cysts may be the cause of false positive
      radioiodine uptake. Endometriosis cyst was not previously described and the
      mecanism of iodine uptake is not clear.

PMID- 10891666
TI  - [Hypersensitivity syndrome : a rare but severe adverse effect of antithyroid
      drugs].
AB  - We report the case of a female patient with a severe hypersensitivity syndrome
      caused by carbimazole. She was treated for Graves' disease for a few weeks when
      she was referred for skin rash, increased liver enzymes and hypereosinophilia. No
      immunological abnormalities were detected. Discontinuation of carbimazole
      resulted in quick recovery. Pathogenesis of the hypersensitivity syndrome is
      discussed. Antithyroid drugs are rarely involved in the syndrome but cases with
      vasculitis have been described. In our patient, the role of excessive dose is
      possible.

PMID- 10891667
TI  - Effect of growth hormone and inhibitors of protein kinase A on IGF-I, oxytocin
      and progesterone release by cultured bovine granulosa cells.
AB  - In our experiments we studied the action of GH on the release of nonapeptide,
      steroid hormones and growth factor, in bovine ovarian granulosa cells, as well as
      the role of cAMP-stimulated protein kinase A (PKA) in the mediation of these GH
      effects. For this purpose, the effects of exogenous bGH (0.001-10 mg/ml), PKA
      blockers KT5720 (100 ng/ml) and Rp-cAMPS (1 mmol), alone and in combination, on
      IGF-I, oxytocin and progesterone secretion were investigated. It was found that
      GH addition to culture medium strongly (p<0.05) stimulated IGF-I (at a
      concentration of 0.01-0.1 mgGH/ml medium), oxytocin (0.01-10 mgGH/ml) and
      progesterone (0.01-1 mgGH/ml medium) secretion into the culture medium. PKA
      blockers KT5720 and Rp-cAMPS given alone did not affect release of these
      substances. Rp-cAMPS partially prevented GH effect on IGF-I release, but enhanced
      GH action on progesterone output. KT5720 did not modify action of GH on oxytocin
      release. These observations confirm the involvement of GH in the control of IGF
      I, oxytocin and progesterone release by bovine ovarian granulosa cells. Effects
      of PKA blocker on several GH-induced effects suggest that GH effects on IGF-I and
      progesterone, but not on oxytocin release may be partially mediated by the
      cAMP/PKA-dependent intracellular mechanisms.

PMID- 10891668
TI  - [Multinodular goiter and parotid carcinoma : a new case of Cowden's disease].
AB  - Cowden's Disease is an autosomal dominant genodermatosis associated with
      abnormalities of the breast, thyroid gland, gastrointestinal tract. We describe a
      23-year-old girl who was diagnosed with this disease when she consulted for
      evaluation of a multinodular goiter. Further investigations revealed breast
      lesions, gastric polyposis and parotid cancer. Recognizing Cowden's disease is
      important for prompt screening for malignancies. Skin lesions are markers of
      precancerous development.

PMID- 10891669
TI  - [Pituitary necrosis after spinal anesthesia : a case report].
AB  - Spinal anesthesia was administered to a patient for the surgical reduction of an
      inguinal hernia. However, the procedure was complicated by corticotropic
      insufficiency secondary to the necrosis of a non-secretory hypophyseal adenoma.
      The clinical presentation is discussed here together with both medical and
      neurosurgical managements. Etiology and pathophysiological mechanisms of this
      complication are analyzed in accordance with the most recent of the literature.

PMID- 10891670
TI  - [Guideliness for drug treatment of type 2 diabetes mellitus].

PMID- 10891709
TI  - [ [In Process Citation]

PMID- 10891710
TI  - [Heat shock proteins].

PMID- 10891711
TI  - [Expression of heat shock proteins in salivary gland tumors. Immunohistochemical
      study of HSP27, HSP70, HSP90, and HSP110: apropos of 50 cases].
AB  - Heat shock proteins (HSPs) are known to be increased in response to biological
      stress. Recently some authors described their presence in tumors. Our
      immunohistochemical investigations revealed the expression of HSP27, HSP70, HSP90
      and HSP110 in most of benign tumors of salivary glands (33 cases). In the
      malignant tumors, the reaction was immunopositive for HSP70 and HSP90 in 13/17
      cases; but HSP27 and HSP110 were only expressed in 5/17 cases. In conclusion HSPs
      were expressed less in malignant than in benign cells. These results suggest that
      the loss of some HSPs may be a possible sign of malignancy.

PMID- 10891712
TI  - [Solid cell nests and thyroid pathologies. Retrospective study of 1,390
      thyroids].
AB  - Solid Cell Nests (SCN) of the thyroid gland were considered as embryonic remnants
      or as squamous metaplasia of follicular epithelium. In a retrospective study of 1
      390 thyroids, SCN were found in 9.7 % of thyroids (16 % men and 8 % women, chi(2)
      : p <0, 01). The number of SCN rises with increasing number of sections examined.
      No statistical differences were found with age or thyroid disorders and presence
      of SCN, excluding the metaplastic theory. SCN contained in 38 % of cases,
      neuroendocrine cells (calcitonin and/or calcitonin gene related peptide,
      chromogranin A) and thyroglobulin cells was observed in 78.3 % of SCN. The
      different cell types of SCN fitted with the ultimobranchial remnant theory. Thus,
      some rare carcinomas (like mixed medullary and vesicular carcinoma or
      mucoepidermoid carcinoma) might originate from SCN.

PMID- 10891713
TI  - Krukenberg tumor: a clinico-pathological study of 15 cases.
AB  - Krukenberg tumor clinically mimics primary ovarian cancer. We report a series of
      15 cases of Krukenberg tumor. The patients' age range from 13 to 71 years. Most
      ovarian tumors (14/15) were bilateral. A primary digestive tumor was diagnosed
      pre-operatively in 3 cases, per-operatively in 3 cases and post-operatively in 4
      cases. No primary tumor was identified in the 5 other cases. Histological
      diagnosis of Krukenberg tumor is usually easy either on paraffin or frozen
      sections. Mucin stains are helpful. Two main histological types were found in our
      series : the classic form with sarcoma-like storiform tumoral stroma and an
      alternative cellular-acellular pattern. Mucinous carcinoid was microscopically
      challenged in two cases. Most patients died within 2 years (median survival 14
      months). Nor surgery, neither chemotherapy is efficient but bilateral
      oophorectomy should be proposed in post-menopausal women with gastric linitis
      removed surgically.

PMID- 10891714
TI  - [Do heat shock proteins present an interest for pathologists?].

PMID- 10891715
TI  - [In situ PCR].

PMID- 10891716
TI  - [Solid and pseudopapillary tumor of the pancreas: immunohistochemical and
      ultrastructural study of 2 pediatric cases].
AB  - We report 2 cases of solid and pseudopapillary tumors of the pancreas occurring
      in female children. Lesions were made of uniform small cells arranged in solid
      areas associated with pseudopapillary and cystic patterns. Immunohistochemistry
      study was positive for neuron-specific enolase, alpha-1 anti-trypsin and
      vimentin. Ultrastructural study showed an abundant cytoplasm, rich in
      mitochondria, containing a lot of granules of variable sizes, often
      disintegrated, and some lipid droplets. The differential diagnosis of this lesion
      included endocrine tumor, pancreatoblastoma and acinar cell carcinoma. It is a
      rare tumor of the pancreas with a favorable prognosis after complete resection.

PMID- 10891717
TI  - [Cellular neurothekeoma, a rare cutaneous tumor. Anatomo-clinical and
      immunohistochemical study of 2 cases].
AB  - Cellular neurothekeoma is an unusual cutaneous tumor described in 1986. We report
      two new cases in 14-year-old girls. Both tumors measured less than one centimeter
      and were located on the forearm and the shoulder. They had a plexiform
      architecture and were developed in the dermis and the dermo-hypodermic junction.
      Spindle and epithelioid tumor cells were immunoreactive for vimentin, NKI-C3,
      NSE, CD68 and smooth muscle actin. There was no recurrence 2 and 7 months after
      the operation. Cellular neurothekeoma is a benign tumor. Its histogenesis is
      still unknown. Histological and immunohistochemical features, with positivity of
      the tumor cells for NKI-C3, a non specific melanocytic marker, and negativity for
      S-100 protein and HMB-45, allow to differentiate cellular neurothekeoma from
      myxoid neurothekeoma and melanocytic tumors.

PMID- 10891718
TI  - [Atypical cellular blue nevus. Apropos of 1 case].
AB  - We report a new case of a cellular blue nevus with clinicopathologic atypia. It
      was a large lesion presenting clinically as a vascular tumor located in the
      middle of the back. It grew for 2 years without skin ulceration. The pathological
      study suggested a cellular blue nevus with moderate nuclear atypia, without any
      atypical mitosis and necrosis. The differential diagnosis such as malignant blue
      nevus and melanoma are discussed in search of a better definition of these rare
      lesions.

PMID- 10891719
TI  - [External iliac artery endofibrosis of the cyclist].
AB  - Arterial endofibrosis is a rare disease usually affecting the external iliac
      artery in highly trained athletes. We report a case of bilateral external iliac
      endofibrosis in a 44-year-old cyclist. Microscopic examination of the resection
      specimen showed an isolated thickening of the arterial intima, and confirmed the
      diagnosis of this entity of unknown etiology.

PMID- 10891720
TI  - [Mesothelial cyst of the adrenal gland].
AB  - We report a case of a mesothelial adrenal cyst which was incidentally discovered
      in a 38-year old woman. The diagnosis was confirmed by an immunohistochemistry
      study. Adrenal cysts are rare. They occur more commonly in female patients during
      the 4th and 5th decades and are usually asymptomatic. Adrenal cysts are divided
      into four groups : parasitic, epithelial, endothelial cysts and pseudocysts. The
      management is still discussed : follow-up, surgical resection or fine-needle
      aspiration.

PMID- 10891721
TI  - [Cysticercosis in Guadeloupe].
AB  - We report two cases of cysticercosis proved by histology, one in the brain, the
      other in the orbit. The first case was observed in a traveller, heavy smoker,
      serologically negative to cysticercosis in whom an isolated cerebral tumoral
      metastasis was suspected and resected. The lesion was centered by a typical
      cysticercus of Taenia solium. The second was a periorbital intramuscular nodule
      observed in a child who had never left our island. The fibroinflammatory nodule
      was centered by a cysticercus with a scolex without rostellum and without
      suckers. Its histological aspect led us to the diagnosis of cysticercosis. Three
      species of Taenia are discussed : T. solium, T. crassiceps and T. bovis. This
      case shows that the human transmission of the disease may exist in Guadeloupe.

PMID- 10891722
TI  - [Lobomycosis: a mycosis seldom observed in metropolitan France].
AB  - We report a case of lobomycosis presenting like a cutaneous tumoral lesion in a
      patient living in Guyana. The causative agent is Loboa loboi. The illness is
      seldom observed in metropolitan France. The epidemiology, the clinical features,
      the course and the treatment are studied. The diagnosis is histological, with the
      morphological features of yeast-like cells.

PMID- 10891723
TI  - [Early isosexual precocious pseudopuberty revealing a juvenile granulosa cell
      tumor in a 3-year-old Congolese girl].
AB  - We describe a juvenile granulosa cell tumor expressed by an early pseudopuberty
      occurring in a 3-year-old black child. Clinically, an endocrine syndrome was
      associated with a pelvic mass and ascites. Hyperoestrogenia and serum
      alphafetoprotein level were biologically detected. Histological examination
      showed typical microscopic features of a granulosa cell tumor. The patient is
      well four years after surgery. Growth and mental development are normal.

PMID- 10891724
TI  - Association of herpes simplex virus encephalitis and paraneoplastic encephalitis 
      a clinico-pathological study.
AB  - A 57 year-old woman developed acute limbic encephalitis and brainstem
      dysfunction. Anti-HU antibodies were repeatedly detected in serum and CSF.
      Postmortem examination showed necrotic and hemorrhagic lesions in the temporal
      lobes characteristic of herpes simplex virus encephalitis, which was confirmed by
      immunocytochemistry, and Purkinje cell loss with proliferation of Bergman glia
      and myelin loss in the external aspect of the dentate nuclei characteristic of
      paraneoplastic encephalitis. PCR-assay performed on temporal tissue extracts was
      positive for HSV-1. There was no identifiable neoplasm. This unusual association
      raises the possibility of a link between the two diseases.

PMID- 10891725
TI  - [Non-Hodgkin lymphoma mimicking renal carcinoma: apropos of 1 case of follicular
      lymphoma].
AB  - Primary renal non-Hodgkin's lymphoma (NHL) is unusual, in contrast to the
      frequent renal involvement in disseminated NHL. We report a case of follicular
      lymphoma presenting initially as a renal mass. In the literature, twenty-seven
      similar cases have been described since 1980. The median age at diagnosis is 64
      years with a male predominance. Clinical and radiological findings generally
      evoke renal carcinoma. Histologically, tumors are usually large B-cell lymphomas.
      The existence of renal non-Hodgkin lymphoma mimicking renal carcinoma must be
      recognized. Such lymphomas can either be primitive or be nodal with a renal
      presentation. Nephrectomy followed by chemotherapy permits long disease free
      survival.

PMID- 10891727
TI  - [Granulomatous gastritis. Apropos of 2 cases].
AB  - We report two cases of granulomatous gastritis, one unexplained, one in the
      setting of Crohn's disease. Granulomatous gastritis is an uncommon entity. An
      etiopathogenetic diagnosis can be reached only by combining the morphological
      examination with clinical and laboratory investigations. Isolated granulomatous
      gastritis is a diagnosis of exclusion, distinct from Crohn's disease,
      sarcoidosis, infections, foreign bodies, malignancy or vasculitis.

PMID- 10891726
TI  - Squamous cell carcinoma developing in an intracranial prepontine epidermoid cyst.
AB  - Intracranial epidermoid cysts represent around 0,2 to 1 % of all intracranial
      tumours. Rare malignant transformation of these benign lesions may occur. A 66
      year-old man presented with a state of confusion. MRI demonstrated a
      heterogeneous signal in front of the pons and ventricular dilatation.
      Cerebrospinal fluid examinations disclosed inflammatory cells. The patient died
      six months after his first admission to hospital. At autopsy, a firm greyish
      tumour (3 cm-long and 1 cm-thick) was present in front of the brain stem encasing
      the basilar artery. Microscopic examination revealed a well-differentiated
      epidermoid carcinoma arising from a cystic lesion whose wall was lined by a
      squamous epithelium with a benign appearance. The walls of all the ventricles
      were lined by carcinomatous cells. There was no leptomeningeal metastasis. Twenty
      three other cases of such squamous cell carcinoma have been reported and most of
      them had died within a few months.

PMID- 10891728
TI  - [Diagnosis with hair].

PMID- 10891729
TI  - [An African conjunctivitis].

PMID- 10891730
TI  - [A needle can hide a lot of things].

PMID- 10891731
TI  - [An unusual bone tumor].

PMID- 10891732
TI  - [A cervical cyst].

PMID- 10891733
TI  - [Large sections in routine breast pathology. A technique adapted to conservative
      surgery].
AB  - Large block macrosectioning of segmental excision specimens for breast cancer,
      and especially ductal carcinoma in situ, provides detailed information regarding
      size of the lesions, extent of spread and margin status which are essential for
      local recurrence risk assessment. However, the expansion of this technique has
      been curbed due to its reputation of being technically difficult, time-consuming,
      costly and providing slides of poor quality. We assessed the feasibility of the
      large section technique and adapted it to the everyday practice of a routine
      pathology laboratory. The time spent cutting a large block on a motorized
      microtome is half the time spent cutting the great number of conventional blocks
      needed to assess the same amount of tissue. Finally, 4 mm-thick stained large
      preparations of high quality are produced within 3 days after receiving the
      specimen. Analysis and report are both more precise and easier since the
      pathologist is saved the trouble of having to mentally re-assemble a great
      quantity of numbered small blocks. 805 primary monobloc segmental excision
      specimens have been examined in this way over the last 50 months period and we
      advocate its use as a standard procedure for breast-conserving surgery specimen
      management.

PMID- 10891734
TI  - [Unusual chronic pancreatitis revealing a cystic fibrosis at an adult age].

PMID- 10891735
TI  - [The French National Society of Gastroenterology recommends systematic organized
      screening for colorectal cancer in France].

PMID- 10891736
TI  - [Treatment of Helicobacter pylori infection with lansoprazole 30 mg or 60 mg
      combined with two antibiotics for duodenal ulcers].
AB  - OBJECTIVE: The primary objective of the present study was to evaluate the
      efficacy of 30 and 60 mg of lansoprazole administered in combination with two
      antibiotics for 7 or 10 days in eradicating Helicobacter pylori in duodenal ulcer
      patients. METHODS: This multicenter double-blind study randomized for the
      lansoprazole dose was carried out by 325 gastroenterologists. The H. pylori
      positive diagnosis was based on three antral biopsies (one for a rapid urease
      test and two for histological examination). Eradication was checked by a (13) C
      urea breath test. Patients were given 30 or 60 mg of lansoprazole with 2 g of
      amoxicillin and 1 g of clarithromycin for 10 days or 7 days, followed by 30 mg of
      lansoprazole daily for 18 or 21 days, i.e. the total duration of antisecretory
      therapy was 28 days. RESULTS: Out of the 665 patients included, 620 were analyzed
      on the intent-to-treat basis and 567 on the per protocol basis. The eradication
      rates were significantly higher in the group receiving 60 mg of lansoprazole than
      in the 30 mg group in both the intent-to-treat analysis (P=0.003) and the per
      protocol analysis (P=0.006). In the intent-to-treat analysis 60 mg group, the
      rates (95% confidence intervals) in the 7-day and 10-day sub-groups were 82.5
      (CI: 75.2 - 89.8) and 86.8% (CI: 82.2 - 91.4), respectively, and in the per
      protocol analysis 84.2 (CI: 76.9 - 91.5) and 91.5% (CI: 87.6 - 95.4),
      respectively. With either lansoprazole dose, the eradication rates seemed higher
      when therapy was administered for 10 days. CONCLUSION: The double dose of
      lansoprazole optimizes H. pylori eradication rates. The highest eradication rates
      were obtained after 10 days of therapy. Additional studies should be carried out
      to determine the optimal duration of triple therapy for eradicating H. pylori.

PMID- 10891737
TI  - [Trends for the management of pancreatic adenocarcinoma in a hospitalized-based
      population (1980-1994)].
AB  - OBJECTIVE: To determine the trends for the management of pancreatic
      adenocarcinoma between 1980 and 1994 in a hospital-based population. METHODS:
      Data of patients from the Doubs department and hospitalized for pancreatic
      adenocarcinoma in the University Hospital of Besancon were analyzed. Two study
      periods were determined: 1980-1989 and 1990-1994. RESULTS: One hundred and thirty
      five cases were diagnosed (77 male, 58 female, mean age 65.6 +/- 12.1 years).
      Weight loss (62.3%), pain (52.7%) and jaundice (43.3%) were the most frequently
      reported symptoms. Their proportion and their duration were similar according to
      the period. Diagnosis of the pancreatic tumor was made by ultrasonography or
      tomodensitometry in 97.8% patients. Distribution of tumors according to the AJCC
      staging was unchanged during the study. Pre-operative screening frequently
      underestimated tumor stage, even in the more recent period. The rate of complete
      resection (18.5%) did not increase. The 5-year actuarial survival rate (3.05%)
      remained unchanged. A metastatic spread represented the only independent
      prognostic factor. CONCLUSIONS: The management and the prognosis of pancreatic
      adenocarcinoma have not fundamentally changed. Recent imaging techniques should
      improve staging accuracy. Advances in adjuvant therapies represent a major issue
      for the future.

PMID- 10891738
TI  - [Leptin: physiological aspects and implications in hepato-gastroenterology].

PMID- 10891739
TI  - [Recommendations for cleaning and disinfection procedures in digestive tract
      endoscopy. The French Society of Digestive Endoscopy].

PMID- 10891740
TI  - [New approach to chronic pain in hepato-gastroenterology].

PMID- 10891741
TI  - [Treatment of chronic hepatitis C: present and future].

PMID- 10891742
TI  - [Prevalence of infection by hepatitis viruses in a rural area. Analysis according
      to risk factors and alcohol consumption].
AB  - OBJECTIVES: To evaluate the prevalence of serum markers of hepatitis A, B and C
      viruses in a rural area according to risk factors and alcohol consumption.
      METHODS: Transversal study of unselected subjects living and working in a rural
      area. Each subject included was asked to fill out an anonymous self-administered
      questionnaire dealing with his own risk factors, sexual behaviour and alcohol
      consumption. A blood sample was collected for detection of HBsAg, anti-HBc, anti
      HBs, anti-HAV and anti-HCV antibodies. RESULTS: Three hundred three subjects with
      a mean age of 48 years were included. Main risk factors for viral infection were:
      blood transfusion (9.4%), intravenous drug addiction (0.73%), acupuncture
      (17.5%), tattoos (5. 8%), past hospitalizations (71.5%), homosexuality (1.1%),
      conjugal unfaithfulness (11%), sexual partners >5 (21.3%). Most subjects with at
      risk sexual behaviour had sexual relations without protection. Anti-HAV
      prevalence was 87.2% (95% confidence interval 83.4-91.0%). None of the subjects
      was HBsAg positive and 6.0% (confidence interval 4.7-8.7%) had anti-HBV
      antibodies. HBV prevalence was correlated to homosexuality only. Two subjects
      (0.67%, confidence interval 0-1.6%) without any identified risk factor had anti
      HCV antibodies. There was no correlation between serum viral marker positivity
      and an excess alcohol consumption (>80 g of ethanol/d) which was present in 46
      subjects. However HBV prevalence was 28.6% in the seven subjects who had been
      treated for alcoholism; these 7 subjects had a highly at risk sexual behaviour.
      CONCLUSION: In a rural area, infection by HAV is very frequent. The prevalence of
      HBV and HCV did not greatly differ from that observed in the general and urban
      population. The frequent failure to use protection in subjects with at risk
      sexual behaviour reinforces the need of prevention programs in rural areas.

PMID- 10891743
TI  - [Organized hepatitis C screening. Results and cost of a one-year campaign in a
      pilot area].
AB  - OBJECTIVES: The management and monitoring process and the efficiency of targeted
      hepatitis C screening in the French health care system are not known. We assessed
      the main results and the cost of the program established in the Doubs area, where
      organized screening was integrated into the activities of voluntary physicians.
      METHODS: All biological laboratories in the area, 23% of the private general
      practitioners, 42% of occupational physicians, one prison health service and one
      health centre agreed to participate. Screening was targeted to the following risk
      factors: transfusion before 1991, intravenous drug use, tattooing and household
      contact. The prescription form specified the indication and allowed free testing.
      RESULTS: Among the volunteers, 58% of the general practitioners, 63% of the
      occupational physicians and 50% of the laboratories prescribed at least one
      screening test. In one year, 948 serologies were prescribed, mainly for tattooing
      (45%) or transfusion (28%). Only 83% of the tests were performed, with patient
      observance depending on age, indication and the place of prescription. Thirty-one
      patients were positive (4%). The cost of the campaign was 10 994 F per screened
      case. CONCLUSION: Mobilizing health professionals for organized screening is
      difficult which affects the efficiency of strategies.

PMID- 10891744
TI  - [Interactions between hepatitis C virus and hepatic lipid metabolism].

PMID- 10891745
TI  - [Pre-test].

PMID- 10891746
TI  - [Synopsis: liver transplantation in adults: indications, results and
      postoperative follow-up].

PMID- 10891747
TI  - [Adult liver transplantation. Questions to Pr. Didier Houssin].

PMID- 10891748
TI  - [Answers to the pre-test].

PMID- 10891749
TI  - [Small bowel perforation and occlusion after migration of biliary and
      cystogastric prosthesis].
AB  - We report on two cases of intestinal complications associated with the migration
      of biliary and cystogastrostomy stents. In the first case, intestinal perforation
      occurred after migration of an Amsterdam type biliary stent. In the second case,
      a double pig tail endoprosthesis induced intestinal occlusion which was
      successfully managed without surgery. Complications after intestinal migration of
      biliopancreatic stents are very rare and usually involve the colon. Our
      observations point out the potential gravity of intestinal migration of
      biliopancreatic stents and, as in the second case, the possible resolution of
      stent related intestinal occlusion after medical management.

PMID- 10891750
TI  - [Regression of mesenteric lymph node cavitation syndrome complicating celiac
      disease after a gluten free diet].
AB  - We report the case of a 39-year old woman with celiac disease in association with
      a cavitating mesenteric lymph node, hyposplenism and intra-hepatic
      haematopoiesis. The serious initial clinical picture evoked a diagnosis of non
      Hodgkin lymphoma but was not confirmed on multiple biopsies. Despite the usual
      poor prognostic clinical outcome in such a setting, treatment with a strict
      gluten-free diet resulted in a remarkable persistent improvement in clinical
      status and lead to almost complete regression in radiological signs observed for
      up to 30 months follow-up.

PMID- 10891752
TI  - [Congenital short bowel syndrome with intestinal malrotation: an unusual cause of
      chronic diarrhea].

PMID- 10891751
TI  - [Intrahepatic portocaval shunt: review of the literature, apropos of 1 case].
AB  - We report a case of portal-hepatic shunt which was detected fortuitously by
      ultrasonography in a 66-year-old patient. This abnormality, mainly described in
      cirrhotic liver and rarely in healthy liver, is usually revealed by hepatic
      encephalopathy or glycoregulation disorders. We propose a diagnostic and
      therapeutic approach based on a review of the literature.

PMID- 10891753
TI  - [Klebsiella oxytoca-associated colitis after oral administration of fusidic
      acid].

PMID- 10891754
TI  - [Ovarian granulomas associated with Crohn's disease: an unusual location of the
      disease or a delayed postoperative adverse event?].

PMID- 10891755
TI  - [Loperamide-induced acute pancreatitis].

PMID- 10891756
TI  - [Acalculous acute cholecystitis and viral hepatitis A].

PMID- 10891757
TI  - [Severe acute hepatitis probably induced by nimesulide].

PMID- 10891758
TI  - [Evidence of daily stability of fasting serum bile acid levels in healthy
      volunteers].

PMID- 10891759
TI  - [Life after digestive surgery: where is the evaluation?].

PMID- 10891760
TI  - [Gastroesophageal reflux: functional counterpart of antireflux surgery].

PMID- 10891761
TI  - [Quality of life after gastrectomy and cephalic duodenopancreatectomy].

PMID- 10891762
TI  - [Short bowel, operated bowel].

PMID- 10891763
TI  - [Ulcerative colitis: ileorectal or ileoanal anastomosis?].

PMID- 10891764
TI  - [Quality of life after surgery for rectal cancer].

PMID- 10891765
TI  - [Iron metabolism].

PMID- 10891766
TI  - [Investigation of iron deficiency].

PMID- 10891767
TI  - [Hemochromatosis].

PMID- 10891768
TI  - [ Metabolic hepatosiderosis].

PMID- 10891769
TI  - [Iron and chronic liver disease (excluding genetic hemochromatosis and metabolic
      liver siderosis)].

PMID- 10891770
TI  - [Diagnostic strategy for iron overload in adults (excluding hematologic iron
      overload)].

PMID- 10891771
TI  - [Screening for hepatocellular carcinoma in cirrhotic patients].

PMID- 10891772
TI  - [Morphological and molecular bases of digestive tract carcinogenesis].

PMID- 10891773
TI  - [Problems raised by screening for digestive tract superficial neoplastic
      lesions].

PMID- 10891774
TI  - [Endoscopic diagnosis of superficial neoplastic lesions of the digestive tract].

PMID- 10891775
TI  - [Staging superficial neoplastic lesions of the digestive tract: contribution of
      endoscopic ultrasonography].

PMID- 10891776
TI  - [Endoscopic treatment of superficial cancers of the digestive tract].

PMID- 10891777
TI  - [The foramen rotundum. Anatomy and radiological explorations. Pathology].
AB  - The foramen rotundum is a small canal deeply situated in the base of the skull
      which represents the way of exit of the maxillary nerve, second branch of the
      trigeminal nerve. Its precise individualization and analyse is difficult and
      necessitates a precise and adapted technique as well as a precise knowledge of
      its anatomical relationships. Its represents a frontier area between the endo-
      and exocranial spaces. Its involvement which is preferentially related with
      tumoral pathologies (and particularly with retrograde perineural invasion)
      profoundly modifies the prognosis of the disease and so should allow soon a
      multidisciplinary therapeutic discussion.

PMID- 10891778
TI  - [What is your diagnosis? Granular cell tumor of the pituitary area].

PMID- 10891779
TI  - [MRI technique for brain tumors in adults].

PMID- 10891780
TI  - [MR diffusion and perfusion imaging in clinical practice].
AB  - MR functional imaging, due to the improvement in ultra-speed imaging technology
      such as echo-planar imaging, has become a very powerful technique since the
      beginning of the nineties. This imaging technique is divided into diffusion
      imaging, perfusion imaging and cerebral activation. Diffusion imaging probes the
      mobility of water molecules characterized by a diffusion coefficient called the
      apparent diffusion coefficient (ADC) for biological tissues. Perfusion imaging
      gives hemodynamic information due to the regional cerebral blood volume by the
      use of contrast agents such as chelates of gadolinium carrying strong magnetic
      susceptibility. Both imaging techniques can provide information in a wide
      nosological range : cerebral ischemia, in the acute phase and in case of
      intracranial tumors, contributing to tumoral grading, localizing the site of
      biopsy, and assessing response to therapy (after radiotherapy for example).
      Nevertheless, a wide range of domains remains incompletely studied, for example
      cerebral white matter diseases and neurodegenerative diseases. For clinical
      applications, a precise knowledge of the potentials of both techniques and their
      limitations is needed. Limitations result from the large number of often patient
      related parameters, imaging technique (perfusion) and data analysis. Powerful
      software has been developed in the workstation environment. Thus this imaging
      technique requires up-to-date equipment and close collaboration between clinical
      and research teams for optimal efficiency.

PMID- 10891781
TI  - Cerebellar atrophy following acute phenytoin intoxication.
AB  - A 25-year-old woman was admitted to our hospital with encephalopathy and clinical
      signs of cerebellar dysfunction. She had recently received an overdose of
      phenytoin. On admission, plasma phenytoin level was high (50 microg/ml,
      therapeutic range 10-20 mg/ml). Magnetic resonance imaging showed no signs of
      cerebellar atrophy. The patient's neurological condition improved rapidly after
      withdrawal of phenytoin. Eight months later, the neurological examination
      disclosed minimal cerebellar disorders and magnetic resonance imaging showed
      cerebellar atrophy. Cerebellar atrophy due to acute phenytoin intoxication is
      very unusual but few cases have been reported. The present clinical and
      radiological findings suggest that short-term phenytoin overdose alone may cause
      cerebellar atrophy.

PMID- 10891782
TI  - [The misfortunes of a survey].

PMID- 10891783
TI  - Hearing status of French youth aged from 18 to 24 years in 1997: a cross
      sectional epidemiological study in the selection centres of the army in Vincennes
      and Lyon.
AB  - BACKGROUND: It is currently thought that young adults are at increasing risk of
      exposure to deleterious sources of noise. To test this possibility we have
      assessed hearing status of young French men aged between 18 and 24 years in 1997
      and study risk factors of deafness in a cross-sectional epidemiological study at
      selection centres for aptitudes to National Service. METHODS: During the time of
      the study, 1208 subjects were examined. For each subject, data of an interview,
      an otoscopy and audiograms were collected. We compared hearing thresholds between
      subjects with different noise exposures and we determined risk factors of
      deafness in this population. RESULTS: The prevalence of hearing loss was 9% at
      medium frequencies (0.5-2 kHz) and 15% at high frequencies (4-8 kHz).We found
      that 60% of the subjects were regularly exposed to at least one source of loud
      noise. Acoustic trauma (6%) mostly explained hearing losses. Repeated episodes of
      otitis media in childhood (17%) also emerged as an important risk factor
      apparently due to increased sensitivity to noise. In subjects with antecedent of
      otitis media, hearing impairments were significant in personal stereo users (>1
      hour per day) (p<0.001), in those who went to discos and rock concerts (>2 times
      per month) (p=0.01) and in those who worked in noisy places (p=0.01). In
      contrast, in subjects without antecedent of otitis, we found no difference in
      hearing thresholds between noise exposed and non noise exposed subjects.
      CONCLUSIONS: Loud sound exposure is a true risk factor of early deafness in
      subjects that had had repeated episodes of otitis media in childhood. This study
      stresses the need for both prevention policies and information of health
      professionals and practitioners.

PMID- 10891784
TI  - [Mortality socio-economic inequalities for small-areas in Belgium: assessing
      concentration].
AB  - BACKGROUND: The reduction of socio-economic inequality in mortality is an
      important public health goal. Previous ecological studies aimed at studying the
      relationship between mortality rate and socio-economic factors have paid little
      attention to mortality causes avoidable by primary or secondary prevention.
      Furthermore, these studies do not make the distinction between, on the one hand,
      the strength of the relationship mortality/socio-economic deprivation and, on the
      other hand, the significance of the unequal distribution of mortality. The
      present work is aimed at measuring the strength of this relationship and the
      concentration of mortality in relation to socio-economic deprivation for both
      overall mortality and mortality avoidable by primary and secondary prevention.
      METHOD: Standardised mortality ratios were computed at the community level in
      Belgium (1985-93 period) for all causes and for 11 mortality causes avoidable by
      primary and secondary prevention. A deprivation index was elaborated using a
      factorial principal component analysis on 11 socio-economic indicators. The
      mortality/deprivation relationship was assessed by way of a standardised
      regression coefficient (B) while socio-economic concentration of mortality was
      estimated using the Concentration Illness Index (Cii) and the P90/P10 ratio.
      RESULTS: A strong positive relationship was found between mortality and
      deprivation for under 65 years all-causes mortality (B =0.71; CI [0.66; 0.76]),
      mortality for cirrhosis of the liver (B =0.56; CI [0.51; 0.62]), lung cancer (B
      =0.49; CI [0.42; 0. 56]), suicide (B =0.35; CI [0.29; 0.42]) and falls (B =0.34;
      CI [0. 28; 0.41]). However, the concentration of mortality was more limited: 14%
      (CI [11%-17%]) of cirrhosis of the liver mortality, 7% of fall (CI [5%-10%]) and
      suicide mortality (CI [4%-9%]), 6% (CI [5%-7%]) of lung cancer mortality is
      unequally distributed. CONCLUSION: Socio-economic deprivation is positively
      associated with mortality. This association is more pronounced for tobacco,
      alcohol and mental health related mortality. However, the strength of the
      relationship between socio-economic deprivation and mortality is not a good
      indicator of unequal distribution.

PMID- 10891785
TI  - [Modeling asthma evolution by a multi-state model].
AB  - BACKGROUND: There are many scores for the evaluation of asthma. However, most do
      not take into account the evolutionary aspects of this illness. We propose a
      model for the clinical course of asthma by a homogeneous Markov model process
      based on data provided by the A.R.I.A. (Association de Recherche en Intelligence
      Artificielle dans le cadre de l'asthme et des maladies respiratoires). METHODS:
      The criterion used is the activity of the illness during the month before
      consultation. The activity is divided into three levels: light (state 1), mild
      (state 2) and severe (state 3). The model allows the evaluation of the strength
      of transition between states. RESULTS: We found that strong intensities were
      implicated towards state 2 (lambda(12) and lambda(32)), less towards state 1
      (lambda(21) and lambda(31)), and minimum towards state 3 (lambda(23)). This
      results in an equilibrium distribution essentially divided between state 1 and 2
      (44.6% and 51.0% respectively) with a small proportion in state 3 (4.4%).
      CONCLUSIONS: In the future, the increasing amount of available data should permit
      the introduction of covariables, the distinction of subgroups and the
      implementation of clinical studies. The interest of this model falls within the
      domain of the quantification of the illness as well as the representation allowed
      thereof, while offering a formal framework for the clinical notion of time and
      evolution.

PMID- 10891786
TI  - [The financial impact of maintenance treatment in heroin addictive behavior: the
      case of Subutex].
AB  - BACKGROUND: The development of maintenance treatment for subjects with addictive
      behavior is an important public health issue. As such, the social effectiveness
      of maintenance products must be examined from an economical and social point of
      view. This paper aims at presenting the financial costs involved in the use of
      Subutex, a product commercialized since 1996. METHODS: A complete typology of
      costs related to drug addiction and its consequences was set up. Some of these
      costs were estimated on the basis of data drawn from the literature. The cost of
      Subutex use for maintenance treatment was assessed and compared with the
      financial stakes including the potential reduction of the economic and social
      cost of drug addiction. RESULTS: Monthly treatment cost of Subutex was 1252 FrF
      per drug abuser on maintenance treatment. By extrapolation, for a population of
      40,000 drug abusers, the direct medical cost of Subutex during a course of
      maintenance treatment with general practitioner follow-up was estimated at 600
      millions FrF. US data sources were applied to France to assess the cost of
      illnesses attributable to drug addiction. The cost reached 4.8 billions FrF. The
      cost of delinquency associated with drug addiction, which mostly concerns money
      laundered to purchase substances was an estimated 6.4 billions FrF. Finally, the
      cost of public anti-drug abuse programs was nearly 4.7 billions FrF. Thus, the
      direct cost of drug addiction consequences reached 15.6 billions FrF. This cost
      should be compared with the annual cost of Subutex for public organizations which
      was an estimated 600 millions FrF. CONCLUSIONS: The "profit" threshold of
      maintenance treatment with Subutex in terms of direct costs is very low. A
      decrease of only 4% of the costs associated with drug addiction would make it
      possible to balance the financial budget for the community. Our analysis does not
      take into acount absolutely all the public health and safety aspects involved in
      the use of Subutex. It does however provide a useful assessment of the financial
      aspects of the question and justification for this therapeutic strategy from a
      budgetary point of view.

PMID- 10891787
TI  - [Epidemiology of in-line skate injuries: state of the art].
AB  - During the last decade, in-line skating has become an increasingly popular
      activity. Along with the number of reports, highlighting the number of injuries
      and their degree of severity, in-line skating injuries have to be considered a
      growing public health issue. The objective of this work is to report
      epidemiological knowledge about in-line skate injuries and ways of prevention. A
      thorough search of all reports and publications on the subject was performed
      through the Medline database and in references of selected publications. There
      are numerous case series studies and several observational ones, most of them
      undertaken in North America. In-line skates are used for recreation, sports, and
      transportation, in a variety of settings (parks, streets, bike path, etc.) and by
      most of age groups (5 to 71 years, median generally about 15). The most common
      site of injury is the wrist and forearm, although other parts of the body can be
      severely injured. Age, sex, physical training level, formal instruction level,
      lack of wearing of protective gear, skating location, may be risk factors for
      injury. Some preventive measures were proposed by a number of research workers
      (information campaigns, wearing of protective gear, instruction, laws, etc.).
      Several preventive attempts were undertaken but no one was appraised. In-line
      skates are used by all age groups and for a variety of activities. In-line
      skating is related to a great number of factors, such as cultural, social,
      geographic, urban and behavioural factors. Therefore, groups at risk for injury
      are very different. Emergence of an important type of injury should lead to the
      development of analytic epidemiological studies, based on particular groups of in
      line skaters, in order to describe them, to identify and quantify risk factors
      and to design preventive measures, and then to appraise their efficiency.

PMID- 10891788
TI  - [General population exposure to dioxins, human ubiquitous pollutants].
AB  - This paper gives an overview of the environmental or background exposure of
      general population to dioxins, polychlorinated dibenzo-para-dioxins (PCDD) and
      polychlorinated dibenzofurans (PCDF), originating from a variety of industrial
      and thermal processes and recognized as cancerous and toxic substances. The daily
      consumption of low-level contaminated food, mainly of animal origin, leads to the
      accumulation of dioxins in the human body. To determine the background exposure,
      human milk, adipose tissue or blood from many geographical locations (except
      France) have been used as bioindicators for body burden of dioxins. Human milk
      also allows the daily intake estimation of dioxins for breast-fed babies. Efforts
      should be made to minimize or avoid PCDD/PCDF emission in the environment.

PMID- 10891789
TI  - [Oral contraception and genetic factors in breast cancer: characteristics and
      limits of case-only studies].
AB  - The analysis of the interaction between environmental and genetic factors is a
      matter of increasing interest in cancerology. More particularly the discovery of
      the BRCAx family and the high cumulated incidence of familial breast cancers
      related to mutations of these proteins raised the issue of the differential
      effect of long term and/or early exposure to oral contraceptives in the presence
      of these mutations. The classical case-control design assumes the presence of a
      control group, which can be sometimes difficult to obtain from both the technical
      and ethical points of view. Case-only or case-case studies, which are based only
      on series of cases, making them apparently attractive, have been proposed to
      analyze more specifically the interaction term. The aim of the present paper is
      to review and discuss the methodological basis and main assumptions of the case
      only design, and their applicability to breast cancer studies. The measure of the
      interaction between an environmental factor and a susceptibility genetic factor
      differs in an important aspect from the measure of the association between an
      environmental factor and a acquired tumoral genetic factor; this aspect is
      reminded.

PMID- 10891790
TI  - [Smoking prevalence in Andorra: reference for intervention evaluation].

PMID- 10891791
TI  - Announcements

PMID- 10891792
TI  - [Prognosis of multiple sclerosis could be related to damage in white matter with
      a normal MRI appearance].

PMID- 10891793
TI  - [Progress in pediatric neurology].
AB  - A central part of Pediatric Neurology is currently dominated by the search for
      genetic factors involved in developmental disorders of the nervous system,
      including cases where the cytogenetic examination remains uncontributive. The
      prerequisite for a good definition of the malformative phenotypes leads to
      distinguish: 1 cerebral malformations that can be identified at the macroscopic
      scale, by imaging. 2 polymalformative syndromes including mental retardation
      where cerebral imaging is not contributive, thus the syndromatic definition is
      based on associated somatic anomalies. 3 Non-syndromatic mental retardation,
      where a genetic origin is clear only in the familial forms. Various
      methodological approaches have included genetic linkage studies, search for
      inframicroscopic chromosomal rearrangements in the critical region and
      investigation of candidate genes. A great number of syndromes have been connected
      with a great diversity of genetic mechanisms, whose many examples are presented:
      genopathies with regular or variable expression, unstable mutations, contiguous
      gene syndromes or other complex infracytogenetic rearrangements, chromosomal or
      genic mosaicisms, mutations submitted to parental imprinting. New methods of
      genomic screening will be necessary to progress in this field, given the great
      number of genes involved in cerebral development. As for the early developmental
      disorders of the PNS and muscle, their diagnosis becomes frequent during the
      intrauterine life, raising the problem of a better definition of the
      fetopathological phenotypes.

PMID- 10891794
TI  - [Neurology in Paris hospitals, particularly the Salpetriere before Charcot:
      Rostan on brain softening].
AB  - In the beginning of the 19th century, many studies were devoted to the diseases
      of the nervous system in France, long before the work of Charcot. The researches
      of Leon Rostan on the cerebral softening (1819, 1823) were based on the
      anatomoclinic method developed by the School of Paris whose most famous
      representatives were Corvisart and Laennec for the study of heart and lung
      diseases. The researches of Rostan were performed in the Salpetriere hospital
      which was, at this time, an hospice for old women. Rostan was appointed Inspector
      of the Health service in the Salpetriere hospital in 1812 then Head of a
      department in 1818. He was 28 year old when he published his book "Researches on
      the cerebral softening" in 1819. Rostan was the first to describe the spontaneous
      cerebral softening as a special anatomoclinic entity distinct from encephalitis
      and apoplexy. He compared this entity to the senile gangrene and stated that it
      was related to the ossification of cerebral arteries. He described the pathologic
      features of the brain softening and also its clinical symptomatology in
      opposition to that of apoplexy. The concept of brain softening according to
      Rostan was harshly fought by the followers of the Broussais's physiological
      medicine (from Lallemand, 1830 to Calmeil, 1859) who claimed that all brain
      softenings were due to the inflammation process and thus should be described as
      encephalitis. In opposite, the ideas of Rostan were accepted and developed by
      others such as Carswell in England (1835), Abercrombie in Scotland (1836) and
      Andral in France (1827, 1840). These authors agreed that some type of cerebral
      softening was related to a disease of the arterial system. Nevertheless, the
      modern concept of brain softening was not definitively accepted before the
      description of the thromboembolic mechanisms by Virchow in Germany (1856) with
      the help of the microscope, and the anatomoclinic studies of Proust, Laborde and
      Prevost and Cottard in France (1866). The book of Rostan was dedicated to the
      "Conseil General des Hospices" which was created in 1801 to unify the
      administration of the hospitals in Paris and became the "Administration Generale
      de l'Assistance Publique a Paris" in 1849. One hundred and fifty years after its
      publication, the work of Leon Rostan was outstanding by its modernity of the form
      as well as the substance.

PMID- 10891795
TI  - [Non-familial Creutzfeldt-Jakob disease: a study of 53 cases].
AB  - Creutzfeldt-Jakob disease (CJD) is the most frequent human spongiform
      encephalopathy. We have analyzed 53 cases of definite non familial CJD over a
      study period of 28 years. All were autopsied in the same neuropathological unit.
      Clinical and epidemiological data were in accordance with previous studies: low
      incidence of CJD under the age of 40, high incidence around the sixty years of
      age (26%) a sex ratio at 0.65 and high frequency of myoclonus, dementia and
      cerebellar ataxia during evolution (78%). This study highlights the rapidity at
      the onset of the disease (within 24 hours) in 16% of the cases. EEG disclosed
      typical pseudoperiodic activity in only 53% of cases and cerebral MRI showed high
      T2 signal intensity in basal nuclei in 15%. This regional study is the second of
      its nature to be carried out in France, the first one covering the area of Paris.

PMID- 10891796
TI  - [A tridimensional study of lateral grasping and pointing in spatial neglect].
AB  - The aim of this study was to analyze the ipsilateral upper limb and head
      kinematics in patients presenting with spatial neglect, using pointing and
      grasping to object. Four patients were included and compared to an equivalent
      number of normal subjects. Head, shoulder, and wrist movements were recorded
      using a three-dimensional VICON system. Objects to be pointed or grasped were
      localized in the right or left space facing the subject. Patients presented with
      a reduction in the mean wrist velocity, which was more obvious when directed to
      the left side, reduction in the peak velocity, and a severe increase of the time
      between the peak velocity and the end of the movement. The amplitude and mean
      velocity of left head movements were comparable in both groups. The analysis of
      the intersegmental co-ordination showed that the sequence of activation of
      corporeal segments was similar in patients and controls: head movement, shoulders
      rotation, upper limb extension. Co-ordination between head and wrist movements
      was assessed using the cross-correlation method. An increase in time lag and a
      reduction in crossed correlations between the head and wrist movements was
      observed in leftward movements of neglect patients, but the co-ordination between
      the shoulder and wrist movements was preserved. Thus, we demonstrated a global
      disorder of intentional movements in patients, which was relatively similar in
      pointing and grasping to object, and predominated on the approach phase, which is
      associated to important visuo-motor adjustments. This study also demonstrated
      desynchronization of head and wrist movements, which can be an important problem
      in neglect patients.

PMID- 10891797
TI  - [Clinical, biological and genetic study of 24 patients with ataxia telangiectasia
      from southern Tunisia].
AB  - Ataxia telangiectasia is a multisystem disease with an autosomal recessive
      inheritance. It is characterized by progressive cerebellar ataxia, oculocutaneous
      telangiectasia, humoral and cellular immunodeficiencies and high incidence of
      neoplasia and radiosensitivity. A 5 year retrospective survey included 24
      patients belonging to 17 families. Cerebellar ataxia was the first clinical
      symptom and was usually noticed when the child began to walk. Mean age of onset
      was 2.9+/-1.8 years. Oculocutaneous telangiectasia was present in 17 cases and
      appeared between 2 and 8 years and then spread in a characteristic symmetrical
      pattern. When ocular telangiectasia was absent (6 cases), the diagnostic of
      ataxia telangiectasia was retained on oculomotor apraxia (2 cases), recurrent
      sinopulmonary infections (3 cases) and/or a sib with typical ataxia
      telangiectasia (1 case). Recurrent sinopulmonary infections, absence or low serum
      level of IgA (78 p.100) and lymphopenia revealed immunodeficiency. Among 12
      patients, chromosomal instability was observed in 5. Balanced rearrangements
      involving chromosomes 2, 7, 14, 22, 1, 3 and 11. The responsible gene, ATM,
      encodes a large protein kinase with a phosphatidylinositol 3-kinase-like domain.
      Ataxia telangiectasia patients have a 100 fold higher risk of cancer than the
      general population. We reported, in the same family two patients who developed
      neoplasia, (lymphoma and leukemia). During follow-up, a progressive worsening was
      observed in all cases. Three patients have died.

PMID- 10891798
TI  - [Familial multiple sclerosis: study of 357 consecutive patients].
AB  - The empiric recurrence risk of multiple sclerosis (MS) of relatives of French MS
      patients is not known. Using a standardized interview, we collected the family
      histones of 357 consecutive patients followed at our MS clinic; adequate
      information was obtained on 4784 relatives up to the third degree. Thirty-five
      patients (9.8%) had a relative with MS. The risk-curve for relatives was the same
      as in other studies conducted with a similar methodology in Canada. England and
      Flanders. but the crude overall MS recurrence risk for relatives was lower in
      France. The genetic burden of MS may be lower in France than in areas of higher
      MS prevalence.

PMID- 10891799
TI  - [Comparative study of actigraphy and ambulatory polysomnography in the assessment
      of adaptation to night shift work in nurses].
AB  - Night shift work is common in hospitals to assure continuous care. This practice,
      however, induces difficulties due to changes in the sleep/awake cycle of hospital
      workers. The aims of the present study were to validate actigraphy in comparison
      with polysomnography for sleep evaluation and to assess nurses' adaptation to
      sleep/wake cycles when on a permanent night shift schedule. Actigraphy and
      ambulatory polysomnography were performed in fifteen night shift nurses employed
      in hospital on a full time basis, during their work and their rest periods. Our
      first findings showed that actigraphy gave reliable results compared with
      polysomnography in evaluation of total sleep time. In addition, it was found that
      seven of the nurses exhibited, during their work periods, an approximately five
      hour delay in the acrophase of their rest/activity rhythm compared with their
      rest periods. In contrast, five other nurses whose acrophase did not change
      between work and rest periods, exhibited sleep episodes of more than 100 minutes
      duration at work. These results confirm data in the literature and show that some
      nurses cannot adjust the circadian rhythm of their inner biological clock to
      their nocturnal schedules. Actigraphy seems to be an efficient, low cost and easy
      method for measuring total sleep time as well as for assessing the inability of
      nurses to adapt to permanent night shift work.

PMID- 10891800
TI  - [Sumatriptan nasal spray 20mg: efficacy, tolerance and quality of life in
      migraine patients].
AB  - The primary objective of this prospective, open, non controlled, multicenter
      study was to collect data on migraine patients' health related quality of life
      before and after treatment of their migraine attacks by sumatriptan nasal spray
      20 mg over a 12 week period. The impact on health related quality of life was
      evaluated by the mean change from pre-treatment scores french migraine health
      related quality of life specific questionnaire (QVM). A total of 219 patients
      have been included in the study, whose migraine attacks were not usually relieved
      by first line therapy. A statistically significant improvement in health related
      quality of life (as measured by the global score and the four scores related to
      the four dimensions of the QVM questionnaire (functional, psychological, social
      and therapeutic) were observed compared to the pre-treatment score values. At the
      end of the treatment period, 60% of patients preferred sumatriptan nasal spray 20
      mg to their usual treatment. Headache relief was reported 2 hours after
      administration in 66% of attacks treated by sumatriptan nasal spray 20 mg during
      the study period and pain free in 46% of treated attacks. The nature and
      incidence of adverse events were similar to these observed in previous studies
      performed with sumatriptan nasal spray 20 mg and no unexpected events were
      reported. CONCLUSION: Those data suggest for the first time that the use of
      sumatriptan nasal spray 20 mg for the treatment of migraine attacks during a 12
      week period may be associated with a significant improvement in migraine
      patients' quality of life. The clinical efficacy and tolerability results
      observed in this study are similar to those from controlled studies previously
      published with sumatriptan nasal spray 20 mg.

PMID- 10891801
TI  - [Isolated dissection of the basilar artery].
AB  - Two cases of isolated dissection of the basilar artery responsible for ischemic
      stroke are reported. This rare condition is still associated with a poor outcome.
      Most patients were male and the clinical presentation consisted of ischemic
      symptoms or subarachnoid hemorrhage in posterior circulation. Angiography and
      Magnetic Resonance Imaging are usefull for the diagnostic, showing parietal
      hematoma, or as for our first case, double lumens. Optimal therapeutic is
      unknown.

PMID- 10891802
TI  - [Ischemic cerebral vascular accident and zoster infection].
AB  - Herpes zoster is uncommonly followed by cerebral infarction. The
      pathophysiological mechanism remains uncertain. Outcome is favorable after early
      specific treatment. We report the case of a 70-year-old woman who developed right
      hemiparesis with aphasia 15 days after thoracic herpes zoster. The herpes zoster
      induced cerebral vasculitis was hypothesized as no other etiology could be
      identified after detailed assessment of the cerebral infarction including brain
      MRI and cerebrospinal fluid study, and as the clinical course responded to
      antiviral therapy.

PMID- 10891803
TI  - [Paraplegia episodes revealing tuberculous myelitis].
AB  - A 38 year-old woman, without previous medical history, presented, since 1993,
      several paraplegic fits carrying herself progressively through to a severe
      paraplegia. Diagnoses successively proposed were spinal cord compressions by
      slipped discs, spinal cord infarct and multiple sclerosis. In November 1998, the
      patient presented back pain and fever. Spinal cord magnetic resonance imaging
      (MRI) revealed a mildly enlarged dorsal cord with signal abnormalities. The
      lesions were isointense on T1-weighted images, hyperintense on T2-weighted images
      and showed a ringlike contrast enhancement. A lumbar puncture showed a trouble
      cerebrospinal fluid (CSF) with leucocytes 600/mm(3) (85 p.100 polynuclear),
      protein 6.7 g/l, glucose 0.26 g/l, chloride 109 mmol/l. The patient was first
      treated with parenteral unspecific antibiotherapy. Microbiological studies of
      blood and CSF were negative. CSF examination with polymerase chain reaction (PCR)
      was positive for Mycobacterium tuberculosis. Clinical (pain and fever) symptoms
      and CSF abnormalities decreased after antituberculous treatment. However,
      paraparesis remain severe. Spinal tuberculous localizations often lead to
      diagnostic and therapeutic errors. Improvement of spinal cord MRI sequences and
      using of PCR technics in CSF would contribute to reduce these difficulties.

PMID- 10891804
TI  - [Postoperative combined medullary sclerosis revealing Biermer's disease: toxic
      effect of nitrous oxide].
AB  - Combined medullary sclerosis developed suddenly postoperatively in a patient with
      unknown Biermer's disease. The neurological lesions were undoubtedly induced by
      nitrogen protoxide via an inactivation of vitamin B12.

PMID- 10891805
TI  - [Confusional syndrome, language problems, recurrent lower limb motor problems in
      a 48-yr-old man].

PMID- 10891806
TI  - [Motor conduction block].

PMID- 10891807
TI  - [ [In Process Citation]

PMID- 10891808
TI  - [Pharmacologic constraints imposed by the blood-brain barrier: the example of
      multiple sclerosis].

PMID- 10891809
TI  - [Conference reports].

PMID- 10891810
TI  - Glucocorticoids in perinatal medicine: misguided rockets?

PMID- 10891811
TI  - Side effects of steroids revisited.

PMID- 10891812
TI  - A light in the darkness: predicting outcomes for congenital cytomegalovirus
      infections.

PMID- 10891813
TI  - Does heart rate variability explain increased blood pressure in adolescents?

PMID- 10891814
TI  - Postnatal steroids: short-term gain, long-term pain?

PMID- 10891815
TI  - Airway nitrogen oxide measurements in asthma and other pediatric respiratory
      diseases.
AB  - Markers for airway inflammation that can be measured noninvasively in expired air
      may be helpful in treating patients with asthma. For example, levels of nitric
      oxide are high in the breath of children with asthma exacerbations and decrease
      with anti-inflammatory therapy. Expired nitric oxide testing has now been
      standardized and may be useful for children with recurring wheezing that is
      diagnostically or therapeutically challenging. However, the results may be
      influenced by several biochemical and anatomic variables and must therefore be
      interpreted with caution.

PMID- 10891816
TI  - Time course of recovery of adrenal function in children treated for leukemia.
AB  - OBJECTIVE: Many protocols for treating children with early B-cell lineage acute
      lymphoblastic leukemia use 28 consecutive days of high-dose glucocorticoids
      during induction therapy. We prospectively studied the effects of this therapy on
      adrenal function. STUDY DESIGN: Ten children with early B-cell lineage acute
      lymphoblastic leukemia were evaluated by cosyntropin (corticotropin (1-24))
      stimulation testing before initiation of dexamethasone therapy and every 4 weeks
      thereafter until adrenal function returned to normal. RESULTS: All 10 patients
      had normal adrenal function before dexamethasone treatment and insufficient
      adrenal responses 24 hours after completing therapy. Each child felt ill for 2 to
      4 weeks after completing therapy. Although 7 patients recovered normal adrenal
      function after 4 weeks, 3 patients did not have normal adrenal function until 8
      weeks after discontinuing therapy. Statistically significant differences in both
      basal and corticotropin-stimulated cortisol levels were noted when comparing
      tests performed at baseline, 24 hours after completing therapy, and 4 weeks after
      completing therapy. CONCLUSION: High-dose dexamethasone therapy, a standard
      treatment for early B-cell acute lymphoblastic leukemia, can cause adrenal
      insufficiency lasting more than 4 weeks after cessation of treatment. This
      problem might be avoided by tapering doses of glucocorticoids and providing
      supplemental glucocorticoids during periods of increased stress.

PMID- 10891817
TI  - Reduced height in swedish men with asthma at the age of conscription for military
      service.
AB  - OBJECTIVE: To investigate the influence of asthma on growth in Swedish children
      during a period when inhaled corticosteroids (ICS) have been first-line therapy
      for persistent asthma. STUDY DESIGN: We analyzed the height of conscripts with
      and without asthma in the year they turned 18 years old, using Swedish military
      conscription records from 1983, 1986, 1993, and 1996, and assessed exposure to
      ICS using prescription records over the same period. RESULT: The mean height for
      conscripts without asthma was 179.3 cm (SD = 6.6 cm, n = 164,503) and for
      conscripts with asthma 178.6 cm (SD = 6.6 cm, n = 8,531, P <.001). The severity
      of asthma had a negative correlation with height in all study populations (P
      <.001 in each year tested). Since 1985, increasing numbers of children with
      asthma have been treated with ICS in Sweden. Sales of ICS for males from birth to
      age 19 years increased from 68,000 daily doses in 1983 to more than 3, 000,000 in
      1995-1996. During this period, there was no statistically significant change in
      the height difference between conscripts with and without asthma. CONCLUSION: The
      introduction of inhaled steroids in Sweden, where budesonide is the predominant
      medication, has not changed the mean difference in heights between Swedish
      conscripts with and without asthma.

PMID- 10891818
TI  - Nighttime salivary cortisol measurement as a simple, noninvasive, outpatient
      screening test for Cushing's syndrome in children and adolescents.
AB  - OBJECTIVE: There is currently no optimal test to screen for endogenous Cushing's
      syndrome (CS) in children. Traditional 24-hour urine or midnight serum cortisol
      values may be difficult to obtain or elevated by venipuncture stress. We
      hypothesized that salivary cortisol measurement is a reliable way to screen for
      CS in children. STUDY DESIGN: Sixty-seven children (5-17 years) were studied: 24
      obese volunteers, 29 non-obese volunteers, and 14 children with CS. Saliva was
      obtained at 7:30 AM, bedtime, and midnight for measurement of free cortisol by
      radioimmunoassay. RESULTS: Salivary cortisol was detectable in all morning and
      evening samples from patients with CS but was frequently undetectable in healthy
      children at bedtime (66%) and at midnight (90%). With cut points that excluded
      healthy children, a midnight salivary cortisol value of 7.5 nmol/L (0.27
      microg/dL) identified 13 of 14 patients with CS, whereas a bedtime value >27.6
      nmol/L (1 microg/dL) detected CS in 5 of 6 patients. The diagnostic accuracies of
      midnight salivary cortisol and urinary free cortisol per square meter were the
      same (93%). CONCLUSION: Salivary cortisol measurement at bedtime or midnight
      rules out CS in nearly all cases. Nighttime salivary cortisol sampling is thus a
      simple, accurate way to screen for hypercortisolism in children.

PMID- 10891819
TI  - Effects of growth restriction in early childhood on growth, IQ, and cognition at
      age 11 to 12 years and the benefits of nutritional supplementation and
      psychosocial stimulation.
AB  - OBJECTIVES: (1) To determine whether benefits to growth and cognition remain
      after intervention in growth-restricted children who received psychosocial
      stimulation and nutritional supplementation in early childhood. (2) To
      investigate the extent of the differences in IQ and cognition at age 11 to 12
      years between growth-restricted and non-growth-restricted children. STUDY DESIGN:
      Growth-restricted and non-growth-restricted children were identified at age 9 to
      24 months, at which time the growth-restricted children participated in a 2-year
      randomized trial of nutritional supplementation and psychosocial stimulation.
      Eight years after the interventions ended, the children's growth, IQ, and
      cognitive functions were measured. RESULTS: There were no significant benefits
      from supplementation to growth or cognition. Children who had received
      stimulation had higher scores on the Weschler Intelligence Scales for Children
      Revised full-scale (IQ) and verbal scale and tests of vocabulary and reasoning
      (all P <.05). The growth-restricted children had significantly lower scores than
      the non-growth-restricted children on 10 of 11 cognitive tests. CONCLUSIONS:
      Psychosocial stimulation had small but significant long-term benefits on
      cognition in growth-restricted children. Growth-restricted children had
      significantly poorer performance than non-growth-restricted children on a wide
      range of cognitive tests, supporting the conclusion that growth restriction has
      long-term functional consequences.

PMID- 10891820
TI  - Sustained benefit after 2 years of growth hormone on body composition, fat
      utilization, physical strength and agility, and growth in Prader-Willi syndrome.
AB  - BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS)
      are accompanied by abnormal body composition resembling a growth hormone (GH)
      deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion,
      suggesting a possible therapeutic role for GH treatment. Although recent studies
      have demonstrated short-term benefits of treatment with GH, a critical question
      is whether beneficial changes persist or wane with prolonged therapy. OBJECTIVES
      AND METHODS: Effects of 24 months of GH treatment (1 mg/m(2)/d) on growth, body
      composition, strength and agility, pulmonary function, resting energy
      expenditure, and fat utilization were assessed in 35 children with PWS. Percent
      body fat, lean muscle mass, and bone mineral density were measured by dual-energy
      x-ray absorptiometry. Indirect calorimetry was used to determine resting energy
      expenditure and to calculate the respiratory quotient. RESULTS: Compared with
      baseline evaluations, increased height velocity (SD score -1.1 +/- 2.5 to 2.2 +/-
      2.3; P <. 001), reduced percent body fat (46.4% +/- 8.4% to 40.3% +/- 10.0%, P
      <.001), and improved respiratory muscle function and physical strength and
      agility (sit-ups, weight-lifts, running speed, and broad jump; P <.01) were
      observed after 24 months of GH treatment. A decline in respiratory quotient (0.81
      +/- 0.07 to 0.75 +/- 0.06; P <. 01) and a trend toward increased resting energy
      expenditure were also observed. Changes in response to GH occurred predominantly
      during the initial 12 months of GH therapy. CONCLUSIONS: Children with PWS had
      sustained increases in lean body mass, decreases in percent body fat,
      improvements in physical strength and agility, and increased fat oxidation after
      24 months of GH therapy. However, between 12 and 24 months, the growth rate
      slowed. Consequently, encouraging initial results require even more prolonged
      study to draw conclusions regarding the long-term value of GH therapy in changing
      body composition in children with PWS.

PMID- 10891821
TI  - Eating behavior in Prader-Willi syndrome, normal weight, and obese control
      groups.
AB  - OBJECTIVE: Hyperphagia in Prader-Willi syndrome (PWS) is hypothesized to be due
      to hypothalamic dysfunction; thus the study of individuals with PWS might
      illustrate how hypothalamic dysfunction affects eating behavior. The aim of this
      study was to document the microstructure of the eating behavior in patients with
      PWS and to compare it with that of members of obese and normal weight control
      groups of the same age. STUDY DESIGN: Nine subjects with PWS (age, 10 +/- 4
      years), 20 normal weight subjects (age, 12 +/- 3 years), and 20 obese subjects
      (age, 12 +/- 4 years) were served an excess lunch meal (hash) on a hidden scale
      built into a table and connected to a computer. The plate of food is placed on
      top of the scale, and when the food is eaten, the change in food weight is
      registered continuously. An eating curve is displayed online. After the meal, the
      eating data are fitted to a polynomial, and the computer calculates the amount of
      food eaten, time of consumption, eating rate (initial and total), and rate of
      deceleration. RESULTS: Subjects with PWS were found to have a longer duration of
      eating (P =.04) and a slower initial eating rate (P =. 01) compared with members
      of both obese and normal weight groups. In subjects with PWS, 56% of the eating
      curves were non-decelerating (linear or accelerating) compared with 10% of the
      normal weight group and 30% of the obese group (P =.02). CONCLUSION: The
      microstructure of the eating behavior in subjects with PWS differs from that of
      members of obese and normal weight control groups. Thus the eating behavior found
      in subjects with PWS might be due to decreased satiation rather than increased
      hunger.

PMID- 10891822
TI  - Reduced bone mineral density at diagnosis and bone mineral recovery during
      treatment in children with Graves' disease.
AB  - OBJECTIVES: In children with Graves' disease, the prevalence of osteopenia is
      unknown, and the possible restoration of bone mass by antithyroid treatment has
      not been evaluated. The aim of this study was to prospectively evaluate the bone
      mineral density (BMD) and bone metabolism at diagnosis and after 1 and 2 years of
      medical treatment. Twenty-six children (19 girls and 7 boys) aged 11 +/- 3.4
      years (range 3.4 to 15.3 years) were studied. STUDY DESIGN: BMD of the lumbar
      spine and proximal femur were measured by dual-energy x-ray absorptiometry.
      Values were compared with those of healthy children of similar age, sex, and
      pubertal stage. RESULTS: At diagnosis the mean BMD (standard deviation score
      [SDS]) was significantly reduced in both sites (P <.001) with a preferential loss
      of cortical bone (femoral BMD = -1.7 +/- 1.0 SDS) rather than trabecular bone
      (lumbar spine BMD = -0.8 +/- 1.1 SDS) (P =.003). Severe osteopenia (below -2 SDS)
      was found in 11 (42%) of 26 patients. Osteocalcin was significantly higher than
      in the control group (P <.0001), but other bone metabolism markers were normal.
      During treatment (n = 19) a significant gain in femoral (F = 14.7; P =.001) and
      lumbar spine (F = 5; P =.02) BMD (SDS) was observed, and none of the patients
      showed osteopenia. The annual percent change in the BMD values at the femoral
      (+23% +/- 11% and +6% +/- 4%, respectively, during the first and second years)
      and lumbar spine (+19% +/- 9% and +6% +/- 5%, respectively, during the first and
      second years) sites was greater during the first year than during the second year
      of treatment (P <.02 for femoral, P <.04 for lumbar spine). No significant age
      difference in BMD SD score or in BMD percent change values was observed.
      Osteocalcin returned rapidly to normal values, and all other bone metabolism
      markers remained in the normal range. CONCLUSIONS: In conclusion, severe
      osteopenia was observed at diagnosis in children with Graves' disease but was
      rapidly corrected after 1 and 2 years of treatment. Initial reduced bone mass
      with high bone turnover caused by hyperthyroidism was corrected after 1 year of
      euthyroid conditions.

PMID- 10891823
TI  - Blood pressure and cardiovascular autonomic function in healthy children and
      adolescents.
AB  - OBJECTIVES: To investigate the relationship between blood pressure levels and
      cardiovascular autonomic function in adolescents and preadolescents. STUDY
      DESIGN: We measured variability of beat-to-beat arterial pressure and R-R
      intervals using power spectral analysis in 56 adolescents (aged 13-16 years; mean
      age, 9.0 +/- 1.4 years) and 71 preadolescents (6-12 years; mean age, 13.5 +/- 1.1
      years) in the supine and standing positions. RESULTS: Adolescents had higher
      levels of systolic arterial pressure and lower high-frequency power of RR
      intervals than preadolescents. Correlation between the basal level of arterial
      pressure and autonomic function was observed in adolescents but not in
      preadolescents. In adolescents, multivariate analysis indicated that the basal
      level of arterial pressure was inversely related with the high-frequency power of
      RR intervals and positively with the ratio of low-frequency and high-frequency
      power. No significant relation was found in preadolescents. During standing,
      adolescents had a more marked increase in diastolic arterial pressure, heart
      rate, low frequency of R-R intervals, and low frequency of arterial pressure
      compared with those of preadolescents. Changes in diastolic pressure showed a
      significant negative correlation with changes in high frequency of R-R intervals.
      CONCLUSION: Cardiovascular autonomic function plays an important role in
      increasing blood pressure levels associated with increased modulation of vagal
      tone of the heart after puberty but does not in the preadolescent.

PMID- 10891824
TI  - Ductal shunting, high pulmonary blood flow, and pulmonary hemorrhage.
AB  - OBJECTIVE: To describe the relationship among ductal shunting, estimated
      pulmonary blood flow, and pulmonary hemorrhage in very preterm infants. STUDY
      DESIGN: A total of 126 babies born before 30 weeks' gestation (median gestation
      27 weeks, range 23 to 29 weeks) underwent echocardiography at 5, 12, 24, and 48
      hours of age; measurements included right and left ventricular output, superior
      vena cava flow, and color Doppler diameter of any ductal shunt. Pulmonary blood
      flow was derived from the sum of right ventricular output and estimated ductal
      shunt flow. RESULTS: Twelve (9.5%) babies had a pulmonary hemorrhage at a mean
      age of 38 hours. Compared with the rest of the cohort, these 12 babies were less
      likely to have had antenatal steroids (59% vs 90%) and were less mature (26 weeks
      vs 27 weeks). At the echocardiogram closest to the pulmonary hemorrhage, 11 (92%)
      of the 12 babies had a significant patent ductus arteriosus >1.6 mm in diameter
      (median 2 mm, range 0.7 to 2.4 mm), and the median pulmonary blood flow was 326
      mL/kg/min (range 210 to 598 mL/kg/min). These measurements were significantly
      higher than those found in the rest of the cohort in the same period (median duct
      diameter 0.5 mm [range 0 to 2.9 mm], median pulmonary blood flow 237 mL/kg/min
      [range 107 to 569 mL/kg/min]). At 5-hour echocardiography the babies with
      pulmonary hemorrhage had significantly larger diameter ducts but similar
      pulmonary blood flow. CONCLUSIONS: Pulmonary hemorrhage in preterm babies is
      associated with significant ductal shunting and high estimated pulmonary blood
      flow.

PMID- 10891825
TI  - Cardiac toxicity of intravenous terbutaline for the treatment of severe asthma in
      children: a prospective assessment.
AB  - OBJECTIVE: To examine the cardiac toxicity as measured by elevations in serum
      cardiac troponin T (cTnT) and to compare creatine kinase (CK) and creatine kinase
      MB (CK-MB) and findings on electrocardiography (ECG) as markers of cardiac
      toxicity with cTnT during the infusion of intravenous terbutaline for the
      treatment of severe asthma in children. STUDY DESIGN: Prospective cohort study of
      patients receiving intravenous terbutaline for severe asthma. RESULTS: Only 3
      (10%) of the 29 patients had elevations in cTnT. Each underwent mechanical
      ventilation for >72 hours, which was the earliest point at which cTnT elevations
      were identified. Eighteen (62%) patients had an elevation in CK, and 3 had an
      elevation in CK-MB fraction without an elevated cTnT. Twenty (69%) patients had
      ECG findings consistent with ischemia, and 19 of these patients had the ischemic
      findings on their preterbutaline ECG. Elevations in CK and CK-MB and ischemic
      changes on ECG did not correlate with elevations in cTnT. Both mechanical
      ventilation (P =.02) and prolonged administration (>72 hours) of intravenous
      terbutaline (P =. 02) were significantly associated with elevations in cTnT.
      CONCLUSIONS: We found no clinically significant cardiac toxicity from the use of
      intravenous terbutaline for severe asthma as measured by serum cTnT elevations.

PMID- 10891826
TI  - Increased burden of respiratory viral associated severe lower respiratory tract
      infections in children infected with human immunodeficiency virus type-1.
AB  - OBJECTIVES: To determine the burden of viral associated severe lower respiratory
      tract infections (SLRTI) in human immunodeficiency virus-infected (HIV+) and HIV
      uninfected (HIV-) urban black South African children. METHODS: Children with
      SLRTI aged 2 to 60 months were enrolled between March 1997 and March 1998.
      Monoclonal antibody immunofluorescent testing was performed on nasopharyngeal
      aspirates to detect respiratory syncytial virus (RSV), influenza A and B,
      parainfluenza 1-3, and adenovirus-specific antigens. RESULTS: Of the 990 children
      studied, 44.6% were HIV+. The estimated burden of disease of viral associated
      SLRTI in children under 2 years was increased for RSV, influenza A/B viruses,
      parainfluenza 1-3 viruses, and adenovirus in children who were HIV+ compared with
      children who were HIV- (P <.001). Viral pathogens, however, were identified less
      frequently (15.7% vs 34.8%, P < 10(-5)) and bacterial pathogens more frequently
      (12.5% vs 5.8%, P <.0001) in children who were HIV+ than in children who were HIV
      and had SLRTI. The seasonal peak for RSV in late summer-early autumn observed in
      children who were HIV- was less evident in children who were HIV+ (P =.02).
      Children who were HIV+ and had virus-associated SLRTI had a higher mortality rate
      (7. 5%) than did children who were HIV- (0%, P < 10(-3)). CONCLUSIONS: The
      contribution of viral associated SLRTI differs between HIV+ and HIV- children. In
      HIV+ children in South Africa, RSV isolation is not limited by season.

PMID- 10891827
TI  - Placental transfer and decay of varicella-zoster virus antibodies in preterm
      infants.
AB  - OBJECTIVES: To compare the placental transfer of maternal varicella-zoster (VZV)
      antibodies to preterm and term infants and to investigate antibody decay during
      the first 6 months of life in the preterm infants. STUDY DESIGN: Maternal and
      umbilical cord blood samples were taken from 113 healthy mother-newborn pairs: 64
      term (gestational age > or =37 weeks) and 49 preterm (gestational age < or =35
      weeks). Premature infants were further tested at 1, 2, and 6 months. Anti-VZV
      antibody to membrane antigen was measured with the immunofluorescent technique.
      RESULTS: Preterm infants of gestational age < or =28 weeks had positive cord
      antibody and a geometric mean titer significantly lower than those in preterm
      infants of gestational age 29 to 35 weeks and term infants (25% vs 95% and 95%,
      respectively, P <.001 for each, and 2.5 +/- 2.2 vs 10.5 +/- 2.4 and 12.6 +/- 2.4,
      respectively, P <.001 for each). There was no difference between the preterm 29
      to 35 weeks of gestation and term groups. Fetal-maternal ratios for both preterm
      groups were <1 and were significantly less than the fetal-maternal ratio in the
      term infants. The transfer of maternal antibodies to term infants was
      significantly greater than to the 29- to 35-week preterm infants (P =.01). At 2
      months of age, 25% of 29- to 35-week preterm infants and no preterm infant < or
      =28 weeks had a positive titer. At 6 months of age, all preterm infants were
      seronegative, and the geometric mean titer in both groups declined to
      undetectable levels. CONCLUSION: Transplacental transfer of maternal VZV
      antibodies is diminished in preterm infants. VZV antibody levels are
      significantly lower in preterm infants born at < or =28 weeks' gestational age
      compared with those in preterm infants 29 to 35 weeks' gestational age and term
      infants. Anti-VZV titers decrease to undetectable levels in preterm infants by 6
      months of age or earlier; thus these infants appear to be susceptible to
      chickenpox before the scheduled 12-month vaccination.

PMID- 10891828
TI  - Prenatal indicators of congenital cytomegalovirus infection.
AB  - OBJECTIVE: To assess the validity of a diagnostic protocol designed to predict
      the outcome of newborns of mothers suspected to have primary cytomegalovirus
      (CMV) infection during the first 4 months of pregnancy. STUDY DESIGN: Anti-CMV
      immunoglobulin (Ig) M detection by enzyme immunoassay and immunoblot together
      with the determination of anti-CMV IgG avidity allowed us to classify 456 women
      as (1) uninfected, (2) undergoing either a primary or a recurrent infection, or
      (3) having an undefined serologic condition. Prenatal diagnosis was carried out
      at 21 to 23 weeks' gestation for women. The presence of the virus in the amniotic
      fluid was determined by culture, polymerase chain reaction, and quantitative
      polymerase chain reaction. Macroscopic and histologic examinations were
      undertaken on tissue from aborted fetuses, whereas for newborns culture was
      performed on urine sampled during the first week of life. RESULTS: Congenital
      infections were found exclusively among women undergoing a primary infection. The
      quantitative determination of CMV DNA in the amniotic fluid of at least 10(3)
      genome equivalents gave a 100% certainty of detecting an infected fetus. Higher
      viral loads were associated with fetuses or newborns with symptoms. CONCLUSIONS:
      IgM tests and the IgG avidity determination can identify all women at risk of
      transmitting CMV. Furthermore, a high CMV DNA load in amniotic fluid could be an
      indicator of symptomatic congenital infection at a relatively early stage of
      pregnancy.

PMID- 10891829
TI  - Serum granulocyte colony-stimulating factor levels are not increased in patients
      with autoimmune neutropenia of infancy.
AB  - OBJECTIVE: To assess the role of granulocyte colony-stimulating factor (G-CSF) in
      autoimmune neutropenia (AIN). DESIGN: Serum G-CSF levels were measured in 57
      children with AIN. Two different G-CSF-dependent assays were used: a solid-phase
      "sandwich" enzyme-linked immunosorbent assay and a proliferation assay. Sera from
      healthy persons and from patients with severe congenital neutropenia were used
      for negative and positive controls. RESULTS: The median G-CSF level in healthy
      persons (n = 13) was low, 45.6 pg/mL (range <39 to 141 pg/mL). The median G-CSF
      level in patients with AIN (n = 57) was very similar, 45.5 pg/mL (range <39 to
      2500 pg/mL). Forty-five (79%) of 57 patients with AIN had levels within the range
      of the control group. Seven (12%) had marginally increased G-CSF levels (141 to
      400 pg/mL), and only 5 (9%) had levels higher than 400 pg/mL. The G-CSF levels
      measured by enzyme-linked immunosorbent assay correlated well with levels
      measured by the proliferation assay, thus demonstrating that antibodies present
      in patient sera did not affect the biologic activity of G-CSF. CONCLUSION: G-CSF
      production in AIN is not increased despite the low neutrophil count, similar to
      thrombopoietin in immune thrombocytopenic purpura.

PMID- 10891830
TI  - Predictive value of neonatal neurological tests for developmental outcome of
      preterm infants.
AB  - BACKGROUND: There is a need to identify, as early as possible, infants who are at
      risk for long-term neurological morbidity. METHODS: To predict neurodevelopment
      outcome of preterm infants <30 weeks' gestation in a population of 100 infants,
      we used several neonatal and neurobehavioral tests, including cranial
      ultrasonography, the Prechtl neurological test, quality of spontaneous general
      movements, and quality of sleep-wake organization. RESULTS: The Prechtl test at
      corrected term age and findings on cranial sonograms both had high specificity,
      but the Prechtl test had better overall positive predictive power for normal
      neurological and developmental outcomes at 2 years' corrected age. Developmental
      changes in sleep and the amount of indeterminate sleep did not correlate with
      outcome. Scoring general movement quality did not predict outcome and did not
      augment the positive predictive power of the Prechtl test. CONCLUSIONS: The
      Prechtl test at corrected term age (independent of the other tests) is the best
      positive predictor of normal neurological outcome and Bayley test results at 2
      years' corrected age.

PMID- 10891831
TI  - Coping skills training for youth with diabetes mellitus has long-lasting effects
      on metabolic control and quality of life.
AB  - OBJECTIVE: To determine whether initial effects on metabolic control and quality
      of life associated with a behavioral intervention combined with intensive
      diabetes management (IDM) can be sustained over 1 year in youth implementing
      intensive therapy regimens. STUDY DESIGN: Seventy-seven patients (43 females, 95%
      white) 12 to 20 years (mean = 14.2 +/- 1.9; duration, 8.7 +/- 3.9) electing to
      initiate IDM were randomly assigned to one of two groups: with or without coping
      skills training (CST), which consists of 6 small group sessions and monthly
      follow-up to help youth cope with their lives in the context of diabetes
      management; skills included social problem solving, cognitive behavior
      modification, and conflict resolution. Data were collected before the
      intervention and at 3, 6, and 12 months after the intervention by using the Self
      Efficacy for Diabetes Scale, Children's Depression Inventory, Issues in Coping
      with IDDM, and the Diabetes Quality of Life: Youth scales. Clinical data
      (glycosylated hemoglobin level, height, weight, adverse effects) were collected
      monthly. RESULTS: The CST and IDM groups were comparable at baseline. CST
      subjects had lower glycosylated hemoglobin (P =.001) and better diabetes (P
      =.002) and medical (P =. 04) self-efficacy, and less impact of diabetes on their
      quality of life (P =.005) than youth receiving IDM alone after 1 year. In males,
      CST did not affect adverse outcomes of IDM hypoglycemia, diabetic ketoacidosis,
      and weight gain, but CST decreased the incidence of weight gain (P =.05) and
      hypoglycemia in females (P =.03). CONCLUSIONS: The addition of behavioral
      intervention to IDM in adolescence results in improved metabolic control and
      quality of life over 1 year.

PMID- 10891832
TI  - A 15-year-old boy with fulminant hepatic failure.

PMID- 10891833
TI  - Life-threatening status asthmaticus treated with inhaled nitric oxide.
AB  - Inhaled nitric oxide (NO) was administered to 5 consecutive children with life
      threatening status asthmaticus who required mechanical ventilation and did not
      respond to maximal medical management. Four showed a >20% decrease in baseline
      PaCO(2) (median PaCO(2) = 154 mm Hg, range = 95 to 229 mm Hg) occurring rapidly
      after the administration of inhaled NO. Three children, in addition to the index
      case, received continuous inhaled NO therapy, ranging from 5.5 to 21.5 hours.
      Systemic hypotension was not observed, and the maximum methemoglobin level was
      1.9%. Four children survived to hospital discharge. Although the precise
      mechanism of action is not known, it appears that inhaled NO merits further study
      and may represent a life-saving therapy in this select patient population.

PMID- 10891834
TI  - Serum alpha-fetoprotein levels in Beckwith-Wiedemann syndrome.
AB  - We conducted a retrospective study that compared serial alpha-fetoprotein (AFP)
      concentrations obtained from 22 children with Beckwith-Wiedemann syndrome (BWS)
      with levels established for healthy children. The AFP concentration is greater in
      patients with BWS and declines during the postnatal period at a significantly
      slower rate than what is reported in healthy children. AFP levels obtained in the
      course of routine tumor screening in children with BWS should be interpreted with
      a normal curve established specifically for BWS rather than with previously
      published data for healthy infants and children.

PMID- 10891835
TI  - Neonatal onset of rash in Still's disease.
AB  - We report a neonate with a rash that appeared on the second day of life in
      association with elevated body temperatures and increased C-reactive protein
      levels. The rash was evanescent and recurred on a daily basis during the first
      year of life. At 15 months, the infant developed swelling of the right knee
      joint. Early-onset systemic juvenile rheumatoid arthritis can mimic congenital
      infections and should be considered in the differential diagnosis of neonatal
      exanthemas.

PMID- 10891836
TI  - Plasminogen activator inhibitor-1: defining characteristics in the cerebrospinal
      fluid of newborns.
AB  - We measured plasminogen activator inhibitor-1 levels in the cerebrospinal fluid
      and plasma of newborns with and without posthemorrhagic hydrocephalus. We found
      that plasminogen activator inhibitor-1 levels in the cerebrospinal fluid of
      healthy newborns are <10 mg/mL but are greatly elevated in patients who have
      posthemorrhagic hydrocephalus and correlate directly with cerebrospinal fluid D
      dimer and protein levels.

PMID- 10891837
TI  - Candidal atrial fungus ball with ocular sequelae.

PMID- 10891838
TI  - Asthma therapy in children: nebulizers or metered dose inhalers with holding
      chambers?

PMID- 10891839
TI  - Reply

PMID- 10891840
TI  - Adrenal suppression in children with malignant solid tumors treated with
      megestrol acetate.

PMID- 10891841
TI  - How to decrease errors in dose.

PMID- 10891842
TI  - Nursing, we have a problem!

PMID- 10891843
TI  - Emergency and trauma care: old thoughts, new ideas.

PMID- 10891844
TI  - Application of base deficit in resuscitation of trauma patients.
AB  - Clinical measures, such as blood pressure or urine output, have been the
      traditional methods used to assess tissue perfusion in trauma patients with
      hypovolemia. Hypoperfusion of tissues results in increased levels of lactate and
      carbonic acids. Base deficit is a clinical measure of metabolic acidosis that
      normalizes rapidly with adequate resuscitation and hemorrhage control, and it can
      be used to monitor the initial care of a patient with trauma. The method used to
      measure base deficit is discussed, along with its clinical uses and limitations.
      A case study is used to correlate changes in base deficit with other clinical
      parameters.

PMID- 10891845
TI  - Leah L. Curtin discusses the nursing shortage.

PMID- 10891846
TI  - Getting nurses involved: use of existing databases for pediatric trauma research.
AB  - Nurses are strategically positioned to contribute to the research base of
      practice in pediatric trauma care. Nurses who are new to research and feel
      burdened by the time commitment for data collection may consider analyzing
      existing data from records and registries. Much of the published research in
      pediatric trauma and critical care is the result of descriptive studies that have
      had an impact at all phases of trauma care. The analysis of existing data saves
      time for the researcher and avoids some of the ethical questions and concerns for
      informed consent with this vulnerable patient population. Nurses can make an
      important contribution to the knowledge base and evidence-based care for injured
      children.

PMID- 10891847
TI  - Crash testing. Part. 2: Predicting human injury with computerized dummies.

PMID- 10891848
TI  - Administration of blood products.

PMID- 10891849
TI  - Recall of Clinipad sterile products used in prepackaged procedure kits and trays.

PMID- 10891850
TI  - Assessing your knowledge of fall injuries among older adults.

PMID- 10891852
TI  - Abstracts of the Literature.

PMID- 10891851
TI  - Trauma news today.

PMID- 10891853
TI  - Ration Nursing Care-And Patients Pay.

PMID- 10891854
TI  - Recurring views on the structure and function of the cytoskeleton: a 300-year
      epic.
AB  - Some unnoticed or seldom remembered precedents of current views on biological
      motion and its structural bases are briefly outlined, followed by a concise
      recapitulation of how the present theory has been constructed in the last few
      decades. It is shown that the evolution of the concept of fibers as main
      constituents of living matter led to hypothesizing microscopic structures closely
      resembling microtubules in the 18th century. At the beginning of this period,
      fibers sliding over each other and driven by interposed moving elements were
      envisioned as the cause of muscle contraction. In the following century, an
      account of the mechanism of myofibril contraction visualized longitudinal
      displacements of myosin-containing submicroscopic rodlets. The existence of
      fibrils in the protoplasm of non-muscle cells, a subject of long debate in the
      second half of the 19th century, was virtually discarded as irrelevant or
      fallacious 100 years ago. The issue resurfaced in the early 1930s as a
      theoretical notion--the cytosquelette--nearly two decades before intracellular
      filamentous structures were first observed with electron microscopy. The role
      originally assumed for such fibrils as signal conductors is nowadays being
      reappraised, although under new interpretations with a much wider significance
      including modulation of gene expression, morphogenesis, and even consciousness.
      Since all of the above ancestral conceptions were eventually abandoned, the
      corresponding current views are, to a certain extent, recurrent.

PMID- 10891855
TI  - Rhodopsin transport in the membrane of the connecting cilium of mammalian
      photoreceptor cells.
AB  - The transport of the photopigment rhodopsin from the inner segment to the
      photosensitive outer segment of vertebrate photoreceptor cells has been one of
      the main remaining mysteries in photoreceptor cell biology. Because of the lack
      of any direct evidence for the pathway through the photoreceptor cilium,
      alternative extracellular pathways have been proposed. Our primary aim in the
      present study was to resolve rhodopsin trafficking from the inner to the outer
      segment. We demonstrate, predominantly by high-sensitive immunoelectron
      microscopy, that rhodopsin is also densely packed in the membrane of the
      photoreceptor connecting cilium. Present prominent labeling of rhodopsin in the
      ciliary membrane provides the first striking evidence that rhodopsin is
      translocated from the inner segment to the outer segment of wild type
      photoreceptors via the ciliary membrane. At the ciliary membrane rhodopsin co
      localizes with the unconventional myosin VIIa, the product of human Usher
      syndrome 1B gene. Furthermore, axonemal actin was identified in the photoreceptor
      cilium, which is spatially co-localized with myosin VIIa and opsin. This actin
      cytoskeleton of the cilium may provide the structural bases for myosin VIIa
      linked ciliary trafficking of membrane components, including rhodopsin.

PMID- 10891856
TI  - Sequence and phylogenetic analysis of squid myosin-V: a vesicle motor in nerve
      cells.
AB  - We have shown that vesicles in the axoplasm of the squid giant axon move on actin
      filaments and that movement is inhibited by myosin V-specific antibodies [Tabb et
      al., 1998]. In the study reported in this article, experiments were performed to
      clone and sequence the cDNA for squid brain myosin V. Five proteolytic fragments
      of purified squid brain myosin V were analyzed by direct protein sequencing [Tabb
      et al., 1998]. Based on this sequence information, degenerate primers were
      constructed and used to isolate cDNA clones by PCR. Five clones, representing
      overlapping segments of the gene, were sequenced. The sequence data and the
      previous biochemical characterization of the molecule support the classification
      of this vesicle-associated myosin as a member of the class V myosins. Motif
      analysis of the head, neck, and tail domains revealed that squid MyoV has
      consensus sequences for all the motifs found in vertebrate members of the myosin
      V family of motor proteins. A phylogenetic tree was constructed from a sequence
      alignment by the neighbor-joining method, using Megalign (DNAStar, Madison, WI);
      the resulting phylogenetic tree showed that squid MyoV is more closely related to
      vertebrate MyoV (mouse dilute, chicken dilute, rat myr6, and human myo5a) than
      Drosophila and yeast (myo2, and myo4) myosins V. These new data on the
      phylogenetic relationships of squid myosin V to vertebrate myosin V strengthens
      the argument that myosin V functions as a vesicle motor in vertebrate neurons.

PMID- 10891857
TI  - Biochemical characterisation of the actin-binding properties of utrophin.
AB  - Utrophin is a large ubiquitously expressed cytoskeletal protein that is important
      for maturation of vertebrate neuromuscular junctions. It is highly homologous to
      dystrophin, the protein defective in Duchenne and Becker muscular dystrophies.
      Utrophin binds to the actin cytoskeleton via an N-terminal actin-binding domain,
      which is related to the actin-binding domains of members of the spectrin
      superfamily of proteins. We have determined the actin-binding properties of this
      utrophin domain and investigated its binding site on F-actin. An F-actin
      cosedimentation assay confirmed that the domain binds more tightly to beta-F
      actin than to alpha-F-actin and that the full-length utrophin domain binds more
      tightly to both actin isoforms than a truncated construct, lacking a
      characteristic utrophin N-terminal extension. Both domain constructs exist in
      solution as compact monomers and bind to actin as 1:1 complexes. Analysis of the
      products of partial proteolysis of the domain in the presence of F-actin showed
      that the N-terminal extension was protected by binding to actin. The actin
      isoform dependence of utrophin binding could reflect differences at the N-termini
      of the actin isoforms, thus localising the utrophin-binding site on actin. The
      involvement of the actin N-terminus in utrophin binding was also supported by
      competition binding assays using myosin subfragment S1, which also binds F-actin
      near its N-terminus. Cross-linking studies suggested that utrophin contacts two
      actin monomers in the actin filament as does myosin S1. These biochemical
      approaches complement our structural studies and facilitate characterisation of
      the actin-binding properties of the utrophin actin-binding domain.

PMID- 10891858
TI  - Effect of calyculin A on the surface structure of unfertilized sea urchin eggs.
AB  - Calyculin A, a potent inhibitor of type 1 and type 2A protein phosphatases,
      induces contractile ring formation when applied to unfertilized sea urchin eggs
      [Tosuji et al., 1992: Proc. Natl. Acad. Sci. USA 89:10613-10617]. We report here
      the elongation of microvilli in the unfertilized eggs exposed to calyculin A. The
      elongated microvilli and associated sperm-egg binding sites (egg receptor for
      sperm) then became concentrated into a constriction site corresponding to the
      cleavage furrow. The egg receptor for sperm was also in close connection to the
      microfilaments. Okadaic acid is another known inhibitor of protein phosphatase
      type-1 and type-2A. Its effect, however, is about a hundredfold feebler for type
      1 phosphatase than type-2A. Even after treatment with okadaic acid, no change was
      observed, suggesting that these morphological changes were induced by calyculin A
      solely though its inhibitory effect on the type-1 protein phosphatase.

PMID- 10891859
TI  - Leukotrienes and tyrosine phosphorylation mediate stretching-induced actin
      cytoskeletal remodeling in endothelial cells.
AB  - We studied actin cytoskeletal remodeling and the role of leukotrienes and
      tyrosine phosphorylation in the response of endothelial cells to different types
      of cyclic mechanical stretching. Human aortic endothelial cells were grown on
      deformable silicone membranes subjected to either cyclic one-directional (strip)
      stretching (10%, 0.5 Hz), or biaxial stretching. After 1 min of either type of
      stretching, actin cytoskeletons of the stretched cells were already disrupted.
      After stretching for 10 and 30 min, the percentage of the stretched cells that
      had disrupted actin cytoskeletons were significantly increased, compared with
      control cells without stretching. Also, at these two time points, biaxial
      stretching consistently produced higher frequencies of actin cytoskeleton
      disruption. At 3 h, strip stretching caused the formation of stress fiber
      bundles, which were oriented nearly perpendicular to the stretching direction.
      With biaxial stretching, however, actin cytoskeletons in many stretched cells
      were remodeled into three-dimensional actin structures protruding outside the
      substrate plane, within which cyclic stretching was applied. In both stretching
      conditions, actin filaments were formed in the direction without substrate
      deformation. Moreover, substantially inhibiting either leukotriene production
      with nordihydroguaiaretic acid or tyrosine phosphorylation with tyrphostin A25
      did not block the actin cytoskeletal remodeling. However, inhibiting both
      leukotriene production and tyrosine phosphorylation completely blocked the actin
      cytoskeletal remodeling. Thus, the study showed that the remodeling of actin
      cytoskeletons of the stretched endothelial cells include rapid disruption first
      and then re-formation. The resulting pattern of the actin cytoskeleton after
      remodeling depends on the type of cyclic stretching applied, but under either
      type of cyclic stretching, the actin filaments are formed in the direction
      without substrate deformation. Finally, leukotrienes and tyrosine phosphorylation
      are necessary for actin cytoskeletal remodeling of the endothelial cells in
      response to mechanical stretching.

PMID- 10891860
TI  - Kinetochore "memory" of spindle checkpoint signaling in lysed mitotic cells.
AB  - The spindle checkpoint prevents errors in mitosis. Cells respond to the presence
      of kinetochores that are improperly attached to the mitotic spindle by delaying
      anaphase onset. Evidence suggests that phosphorylations recognized by the 3F3/2
      anti-phosphoepitope antibody may be involved in the kinetochore signaling of the
      spindle checkpoint. Mitotic cells lysed in detergent in the absence of
      phosphatase inhibitors rapidly lose expression of the 3F3/2 phosphoepitope.
      However, when ATP is added to lysed and rinsed mitotic cytoskeletons,
      kinetochores become rephosphorylated by an endogenous, bound kinase. Kinetochore
      rephosphorylation in vitro produced the same differential phosphorylation seen in
      appropriately fixed living cells. In chromosomes not yet aligned at the metaphase
      plate, kinetochores undergo rapid rephosphorylation, while those of fully
      congressed chromosomes are under-phosphorylated. However, latent 3F3/2 kinase
      activity is retained at kinetochores of cells at all stages of mitosis including
      anaphase. This latent activity is revealed when rephosphorylation reactions are
      carried out for extended times. The endogenous, kinetochore-bound kinase can be
      chemically inactivated. Remarkably, a soluble kinase activity extracted from
      mitotic cells also caused differential rephosphorylation of kinetochores whose
      endogenous kinase had been chemically inactivated. We suggest that, in vivo,
      microtubule attachment alters the kinetochore 3F3/2 phosphoprotein, causing it to
      resist phosphorylation. This kinetochore modification is retained after cell
      lysis, producing a "memory" of the in vivo phosphorylation state.

PMID- 10891861
TI  - Stereospecific prevention by 17beta-estradiol of MPTP-induced dopamine depletion
      in mice.
AB  - Neuroprotective activity of estrogens is reported in Alzheimer disease and
      recently has also been suggested for Parkinson disease, a disease affecting more
      men than women. To characterize this estrogenic activity, we studied the effects
      of 17beta- and 17alpha-estradiol treatment (1 microg twice daily 5 days before,
      during the day of four MPTP (15 mg/kg) injections, and for the following 5 days)
      on dopamine striatal toxicity induced by the neurotoxin MPTP in retired breeder
      male C57BL/6 mice. Striatal dopamine concentrations and its metabolites
      dihydroxyphenylacetic acid and homovanillic acid measured by HPLC in MPTP mice
      that received 17beta-estradiol were comparable to control animals, whereas MPTP
      mice treated with saline or 17alpha-estradiol showed important decreases of
      dopamine and its metabolites. Striatal serotonin and its metabolite 5
      hydroxyindoleacetic acid concentrations remained unchanged after MPTP and
      treatments with steroids. Striatal [(3)H]GBR 12935 binding autoradiography to the
      dopamine transporter was as extensively decreased and correlated with dopamine
      depletion in MPTP mice, whereas this transporter mRNA decrease in the substantia
      nigra pars compacta was less pronounced. Treatment with steroids did not
      significantly change [(3)H]GBR 12935 binding, whereas dopamine transporter mRNA
      levels were not significantly different from controls. Under the present paradigm
      in retired breeder male mice, our results show dopaminergic and stereospecificity
      of estradiol to augment dopamine levels in MPTP-lesioned mice without protecting
      against the extensive loss of dopamine terminals and moderate cell body loss.

PMID- 10891862
TI  - Cortical inputs to m2-immunoreactive striatal interneurons in rat and monkey.
AB  - Previous anatomical studies have been unsuccessful in demonstrating significant
      cortical inputs to cholinergic and somatostatinergic striatal interneurons in
      rats. On the other hand, electrophysiological studies have shown that cortical
      stimulation induces monosynaptic EPSPs in cholinergic interneurons. It has been
      proposed that the negative anatomical findings might have been the result of
      incomplete labeling of distal dendrites. In the present study, we reinvestigated
      this issue using m2 muscarinic receptor antibodies as a selective marker for
      cholinergic and somatostatinergic interneurons in the striatum. This was combined
      with injections of either the anterograde tracer biotinylated dextran amine (BDA)
      in the monkey prefrontal cortex or aspiration lesion of the sensorimotor cortex
      in rats. The results showed that, in both species, a small percentage (1-2%) of
      cortical terminals make asymmetric synaptic contacts with m2-immunoreactive
      interneurons in the striatum. Interestingly, the majority of these synapses are
      onto small dendritic spines or spine-like appendages, as opposed to dendritic
      shafts and/or cell bodies. Thus, m2-containing striatal interneurons do receive
      direct cortical inputs and can, therefore, integrate and modulate cortical
      information flow through the striatum. Although the density of cortical terminals
      in contact with individual striatal interneurons is likely to be relatively low
      compared to the massive cortical input to projection neurons, both cholinergic
      and somatostatinergic interneurons display intrinsic properties that allow even
      small and distal inputs to influence their overall state of neuronal activity.

PMID- 10891863
TI  - Altered opioid-mediated control of the spinal release of dynorphin and met
      enkephalin in polyarthritic rats.
AB  - Previous studies showed that spinal opioidergic neurotransmission is markedly
      altered in the polyarthritic rat, a model of chronic inflammatory pain. Present
      investigations aimed at assessing possible changes in opioid-mediated control of
      the spinal outflow of met-enkephalin (ME) and dynorphin (DYN) in these animals.
      Intrathecal (i.t.) perfusion under halothane anesthesia showed that polyarthritis
      was associated with both a 40% decrease in the spinal outflow of ME-like material
      (MELM) and a 90% increase in that of DYNLM. Local treatment with the mu-opioid
      agonist DAGO (10 microM i.t.) inhibited equally (-30%) the MELM outflow in
      polyarthritic and control rats, whereas the delta agonist DTLET (10 microM i.t.)
      also reduced the peptide outflow in controls (-27%) but enhanced it in
      polyarthritic animals (+56%). On the other hand, both DAGO (10 microM i.t.) and
      DTLET (10 microM i.t.) decreased (-40 and -49%) DYNLM outflow in polyarthritic
      rats, but were inactive in controls. Finally, neither MELM outflow nor that of
      DYNLM were affected by the kappa-agonist U50488H (10 microM i.t.) in both groups
      of rats. In all cases, the changes due to active agonists could be prevented by
      specific antagonists which were inactive on their own except the kappa antagonist
      nor-binaltorphimine (10 microM i.t.) that decreased (-38%) DYNLM outflow in
      polyarthritic rats. These data indicate that functional changes in spinal opioid
      receptors may promote enkephalinergic neurotransmission and reduce dynorphinergic
      neurotransmission in polyarthritic rats, thereby contributing to the analgesic
      efficacy of opioids in inflammatory pain.

PMID- 10891864
TI  - Norepinephrine exhibits two distinct profiles of action on sensory cortical
      neuron responses to excitatory synaptic stimuli.
AB  - Located within the central gray of the caudal pons, the locus coeruleus (LC) is
      the sole source of norepinephrine (NE) projections to the forebrain. NE is
      released both tonically and phasically from axonal varicosities in LC efferent
      target circuits. NE has been shown to produce a diverse set of actions, including
      suppression of spontaneous and stimulus evoked discharge, augmentation of
      synaptically evoked excitation, and inhibition and gating of otherwise
      subthreshold synaptic inputs. Utilizing an extracellular in vitro tissue slice
      preparation and microiontophoretic techniques, the dose-dependent actions of NE
      on glutamate-evoked discharges of layer II/III and layer V sensory cortical
      neurons were investigated. Noradrenergic effects were further examined in terms
      of cell and adrenoceptor specificity. The results indicate two exclusive
      modulatory actions of NE: 1) ejection current-dependent suppression of glutamate
      evoked discharge, and 2) ejection current-dependent facilitation of glutamate
      evoked discharge followed by suppression of the maximal facilitated response.
      These effects were observed in both normal and low Ca(2+) / high Mg(2+) bathing
      media, suggesting a postsynaptic site for NE's actions. The facilitation of
      glutamate evoked discharge was selectively mimicked by the alpha-1 agonist,
      phenylephrine, whereas the dose-dependent suppression was mimicked by the beta
      agonist isoproterenol. These results suggest that the suppressant and
      facilitating actions of NE are mediated by beta and alpha-1 receptors,
      respectively. In general, these results are consistent with previous
      demonstrations of NE modulatory actions on central neurons, but indicate that in
      the cerebral cortex these effects are both cell- and receptor-specific.

PMID- 10891865
TI  - Development of fast purinergic transmission in the mouse vas deferens.
AB  - ATP released by sympathetic varicosities of the mouse vas deferens binds to P2X
      receptors which activate fast, ligand-gated channels, resulting in depolarisation
      of smooth muscle cells. We examined the development of fast neuromuscular
      transmission at surface longitudinal smooth muscle fibres of the mouse vas
      deferens. Sympathetic varicosities were visualised using DiOC(2)(5)-fluorescence
      to aid in positioning loose patch electrodes over small sets of sympathetic
      varicosities to record the nerve terminal impulse (NTI) and excitatory junction
      currents (EJCs) evoked during nerve stimulation. At the earliest age at which
      EJCs could be detected, 21 days postnatal (PN), most recording sites rarely
      showed a detectable EJC over 100 trials, even though NTIs were recorded without
      failure. The extent of such intermittence in transmitter release progressively
      declined between 21 and 42 days PN. In addition, the mean amplitude of
      spontaneous EJCs (SEJCs) and EJCs increased by 2- and 2.4-fold, respectively,
      between 21 and 42 days PN. The rise time of EJCs varied widely at each age but
      declined with development (e.g., 7-14 ms at 28 days PN, 3-12 ms at 42 days PN).
      All EJCs were abolished by suramin (100 microM). Fast rise time EJCs were rapidly
      abolished by alpha,beta-methylene ATP (20 microM) while some (34%) of the slower
      rise time EJCs were resistant to rapid desensitisation of this kind. P2X(1) and
      P2X(2) mRNAs were detected by reverse transcription and polymerase chain reaction
      (RT-PCR) to determine whether levels of expression of the receptor subunits might
      explain the increased EJC amplitude. Between 10 and 42 days PN no marked change
      was observed in the P2X(2) receptor mRNA or beta-actin mRNA (control). In
      contrast, the intensity of the RT-PCR band for P2X(1) receptor showed a
      progressive approximately 4.3-fold developmental increase relative to the P2X(2)
      band. These observations suggest that both prejunctional and postjunctional
      mechanisms cause the maturation of fast purinergic junctional transmission at the
      longitudinal muscle of the mouse vas deferens between 21 and 42 days PN.

PMID- 10891866
TI  - Autoradiographic evidence that prolonged withdrawal from intermittent cocaine
      reduces mu-opioid receptor expression in limbic regions of the rat brain.
AB  - Numerous reports support evidence that dopaminergic mesolimbic pathways interact
      with opioid systems to influence the reinforcing properties of cocaine.
      Withdrawal from chronic administration of cocaine in rats causes an upregulation
      of mesocorticolimbic mu-opioid receptors during early stages, but information
      about prolonged cocaine abstinence is lacking. We addressed this issue by
      treating rats with cocaine or saline (control) intermittently (1 mg/kg, i.v.,
      every 12 min for 2 h daily) for 10 days followed by a 10- or 20-day withdrawal
      period. The animals were then decapitated and the brains removed for quantitative
      in vitro autoradiographic analysis of 14 brain regions with (125)I-DAMGO. A
      separate group of animals received two consecutive cycles of the 10-day
      cocaine/10-day withdrawal regimen. Only the group that participated in the two
      consecutive cycles showed a significant effect of treatment: downregulation of mu
      opiate receptors in limbic cortical layer 3 (17% lower than saline-treated
      controls, P = 0.03), the core of the nucleus accumbens (16% decrease, P = 0.05),
      and the nucleus of the diagonal band (18% decrease, P = 0.05). The mu-receptor
      may manifest, as do other neural markers (e.g., dopamine transporter, dopamine
      efflux), a biphasic temporal pattern with upregulation during early phases of
      cocaine withdrawal but a downregulation at later times.

PMID- 10891867
TI  - Increased behavioral response to dopaminergic stimulation of the subthalamic
      nucleus after nigrostriatal lesions.
AB  - Local infusions of the nonselective dopaminergic agonist apomorphine into the
      subthalamic nucleus of rats has been shown to elicit orofacial dyskinesia which
      can be blocked by D1 but not D2 receptor antagonists. In the present study, we
      show that the selective D1 agonist A77636 also induces orofacial dyskinesia when
      injected into the subthalamic nucleus of awake rats, thus confirming a role for
      D1 receptors in this effect. We also examined the dyskinesia induced by
      intrasubthalamic injections of apomorphine in rats with an ipsilateral lesion of
      the nigrostriatal pathway. The orofacial response to local administration of
      apomorphine (1.0 microg) into the subthalamic nucleus was markedly increased in
      the lesioned rats. As in control rats, the enhanced behavioral response seen in
      lesioned rats was blocked by peripheral administration of D1 antagonists.
      Although D1 receptor binding autoradiography revealed no difference in D1
      receptor binding in the subthalamic nucleus on the side of the lesion compared to
      controls, D1 binding was higher in the subthalamic nucleus on the side of the
      lesion compared to the contralateral side. The increased behavioral response
      observed after unilateral dopamine denervation suggests that the subthalamic
      nucleus is tonically regulated by dopaminergic projections from the substantia
      nigra. Furthermore, the data suggest that subthalamic D1 receptors may be
      involved in the development of dyskinesia induced by dopaminergic drugs.

PMID- 10891868
TI  - Science before the CD-ROM.

PMID- 10891869
TI  - Experimental infection of monkeys with Langat virus II. Turnover of circulating
      virus, 1967.

PMID- 10891870
TI  - Clinical uses of non-nucleoside reverse transcriptase inhibitors.
AB  - Three non-nucleoside reverse transcriptase inhibitors (NNRTIs) are currently
      available for treatment of HIV-1 as part of combination antiretroviral therapy.
      Oral dosing is administered three times daily for delavirdine (DLV), twice daily
      for nevirapine (NVP), and once daily for efavirenz (EFV). Rash is a common side
      effect of all three NNRTIs, and early CNS side effects are also frequent with
      EFV. Hepatotoxicity is relatively uncommon but requires appropriate monitoring.
      Drug interactions mediated by the cytochrome P450 system are an important
      consideration when the NNRTIs are administered concomitantly with other drugs,
      including protease inhibitors (PIs). HIV strains with reduced susceptibility to
      NNRTIs can occur with a single mutation in the reverse transcriptase (RT) gene.
      The available NNRTIs exhibit overlapping genotypic resistance patterns, but newer
      agents may overcome this problem. NNRTIs have been studied in combination with
      nucleoside RT inhibitors for first-line HIV therapy, where they have shown at
      least equivalent antiviral efficacy compared with PI-based regimens over 1-2
      years of therapy. NVP and EFV have also been studied as a replacement for a PI
      within a virologically successful regimen, with the aim of preventing or reducing
      PI toxicities and simplifying the dosing regimen. Such 'switch' strategies are
      successful for certain patients in maintaining virologic suppression for 6 months
      or more and result in varying degrees of improvement in PI-associated toxicities.
      NNRTIs may offer a benefit when included in salvage regimens for patients failing
      PI-based therapy, particularly in patients who have not previously been treated
      with NNRTIs. NVP has been shown to have a substantial favourable impact on the
      rate of vertical HIV-1 transmission with a simple, cost-effective regimen.

PMID- 10891871
TI  - Incidence and impact of resistance against approved antiretroviral drugs.
AB  - More than 15 antiretroviral drugs are now available for clinical use, and have
      led to significant reductions in morbidity and mortality for HIV infected
      individuals. Nevertheless, antiviral drug resistance emerges to all these drugs,
      which limits their benefit. This review addresses the biological basis of
      antiretroviral drug resistance, and the prevalence of specific drug resistance
      associated mutations in patients treated with the three currently available
      classes of agents, namely nucleoside analogue reverse transcriptase inhibitors,
      non nucleoside reverse transcriptase inhibitors and protease inhibitors. In
      addition, data on prevalence of HIV drug resistance in untreated individuals
      published to date are summarised, and the implications of potential transmission
      of drug resistant HIV is discussed.

PMID- 10891872
TI  - Novel compounds in preclinical/early clinical development for the treatment of
      HIV infections.
AB  - Virtually all the compounds that are currently used, or under advanced clinical
      trial, for the treatment of HIV infections, belong to one of the following
      classes: (i) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), (ii)
      non-nucleoside reverse transcriptase inhibitors (NNRTIs) and (iii) protease
      inhibitors (PIs). In addition to the reverse transcriptase and protease step,
      various other events in the HIV replicative cycle are potential targets for
      chemotherapeutic intervention: (i) viral adsorption, through binding to the viral
      envelope glycoprotein gp120 (polysulphates, polysulphonates, polyoxometalates,
      zintevir, negatively charged albumins); (ii) viral entry, through blockade of the
      viral coreceptors CXCR4 and CCR5 [bicyclams (AMD3100), polyphemusins (T22), TAK
      779]; (iii) virus-cell fusion, through binding to the viral glycoprotein gp41 [T
      20 (DP-178), siamycins, betulinic acid derivatives]; (iv) viral assembly and
      disassembly, through NCp7 zinc finger-targeted agents [2,2'-dithiobisbenzamides
      (DIBAs), azadicarbonamide (ADA)]; (v) proviral DNA integration, through integrase
      inhibitors such as L-chicoric acid; (vi) viral mRNA transcription, through
      inhibitors of the transcription (transactivation) process (peptoid CGP64222,
      fluoroquinolone K-12, Streptomyces product EM2487). Also, in recent years new
      NRTIs, NNRTIs and PIs have been developed that possess, respectively, improved
      metabolic characteristics (i.e. phosphoramidate and cyclosaligenyl pronucleotides
      of d4T), or increased activity against NNRTI-resistant HIV strains, or, in the
      case of PIs, a different, non-peptidic scaffold. Given the multitude of molecular
      targets with which anti-HIV agents can interact, one should be cautious in
      extrapolating from cell-free enzymatic assays to the mode of action of these
      agents in intact cells. A number of compounds (i.e. zintevir and L-chicoric acid,
      on the one hand; and CGP64222 on the other hand) have recently been found to
      interact with virus-cell binding and viral entry in contrast to their proposed
      modes of action targeted at the integrase and transactivation process,
      respectively.

PMID- 10891873
TI  - Alterations in neurochemistry during retinal degeneration.
AB  - Retinitis pigmentosa refers to a family of hereditary retinal degenerations that
      lead to photoreceptor death and vision loss. The underlying cause(s) are not
      known. In recent years there has been accumulating evidence of neurochemical
      changes during degeneration. In particular, the amino acids glutamate, GABA, and
      glycine show alterations in labelling intensity in subsets of neurons.
      Furthermore, there are differences in the labelling of the precursors, glutamine
      and aspartate, prior to, during, and following loss of photoreceptors, suggesting
      that the metabolic pathways involved in neurotransmitter formation and
      degradation may be abnormal. In addition, there is an elevation in glutamine and
      arginine content within Muller cells prior to the onset of photoreceptor death.
      Investigations evaluating Muller cell function indicate that formation and
      degradation of glutamate, in particular, is abnormal in the degenerating retina
      from an early age. These studies suggest that even though the primary genetic
      defect of the RCS rat is within the retinal pigment epithelium, Muller cells
      develop abnormally, and may contribute to the observed photoreceptor loss.

PMID- 10891874
TI  - Somatostatin and somatostatin subtype 2A expression in the mammalian retina.
AB  - This review discusses the expression and cellular localization of the
      neuropeptide somatostatin (SRIF) and one of the SRIF subtype (sst) receptors,
      sst(2A) in the mammalian retina. SRIF immunoreactivity is predominantly localized
      to a sparse population of amacrine and displaced amacrine cells in the ganglion
      cell layer in several mammalian retinas including the rat, rabbit, cat, and
      primate. These cells, characterized by multiple processes, form a sparse network
      in the inner plexiform layer (IPL) in all retinal regions. Very few processes are
      also in the outer plexiform layer. In contrast to the predominant distribution of
      SRIF processes to the IPL, there is a widespread distribution of sst(2A)
      immunoreactivity to both the inner and outer retina in all mammalian retinas
      studied to date. In rabbit retina, sst(2A) immunoreactivity is predominant in rod
      bipolar cells and in sparse wide-field amacrine cells. In the rat retina, sst(2A)
      immunoreactivity is localized to several neuronal cell types-cone photoreceptors,
      horizontal cells, rod and cone bipolar cells, and amacrine cells. Reverse
      transcriptase-polymerase chain reaction analysis found that sst(2A) mRNA is
      expressed in the rat retina, while sst(2B) mRNA is not detected. Finally, in the
      primate retina sst(2) immunoreactivity is predominant in cone photoreceptors,
      with additional immunostained cell bodies and processes in the inner retina.
      These findings indicate that SRIF may modulate several neuronal cell types in the
      retina, and that it has a broad influence on both scotopic and photopic visual
      pathways.

PMID- 10891875
TI  - Neuronal nitric oxide synthase immunoreactive neurons in the mammalian retina.
AB  - The development of immunocytochemistry has led to a better understanding of
      synaptic transmission carried out by neuroactive substances in the mammalian
      brain, including the retina. In the mammalian retina, nitric oxide (NO) is widely
      accepted as a neuromodulator. Histochemistry based on NADPH-d and
      immunocytochemistry based on nitric oxide synthase (NOS) have been used to
      identify the presence of nitric oxide in the mammalian retina. Certain types of
      amacrine cells and a class of displaced amacrine cells have been labeled
      consistently in all mammalian retinae studied to date. Other cell types showing
      NADPH-d reactivity or NOS immunoreactivity varied between species. NADPH-d
      reactive or NOS immunoreactive amacrine cells may serve as a source of NO for
      amacrine, bipolar, and ganglion cells in the inner retina, whereas interplexiform
      cells, bipolar cells, and horizontal cells may serve as a source of NO for the
      outer retina of mammals.

PMID- 10891876
TI  - Neurotrophins and development of the rod pathway: an elementary deduction.
AB  - The rodent retina is a particularly attractive model for the study of neuronal
      developmental processes since considerable neurogenesis, cellular migration,
      phenotypic differentiation of retinal cell types and synaptogenesis occurs
      postnatally. In addition, the retina is readily accessible to surgical
      intervention, pharmacological manipulation, and local suppression of gene
      expression-tools that can be utilized to study mechanisms underlying the
      development of retinal neurons and their interconnections that form distinct
      functional circuits. Here, I review our studies describing the ontogeny of a
      specific retinal interneuron, the AII amacrine cell, an integral element in the
      rod (scotopic) pathway. Specifically, we used a number of approaches to examine
      the potential role of neurotrophic factors on the morphological and neurochemical
      differentiation of the AII.

PMID- 10891877
TI  - Distribution of GABA and glycine receptors on bipolar and ganglion cells in the
      mammalian retina.
AB  - The amino acids GABA and glycine mediate synaptic transmission via specific
      neurotransmitter receptors. Molecular cloning studies have shown that there is a
      great diversity of GABA and glycine receptors. In the present article, the
      distribution of GABA and glycine receptors on identified bipolar and ganglion
      cell types in the mammalian retina is reviewed. Immunofluorescence obtained with
      antibodies against GABA and glycine receptors is punctate. Electron microscopy
      shows that the puncta represent a cluster of receptors at synaptic sites. Bipolar
      cell types were identified with immunohistochemical markers. Double
      immunofluorescence with subunit-specific antibodies was used to analyze the
      distribution of receptor clusters on bipolar axon terminals. The OFF cone bipolar
      cells seem to be dominated by glycinergic input, whereas the ON cone bipolar and
      rod bipolar cells are dominated by GABAergic input. Ganglion cells were
      intracellularly injected with Neurobiotin, visualized with Streptavidin coupled
      to FITC, and subsequently stained with subunit specific antibodies. The
      distribution and density of receptor clusters containing the alpha1 subunit of
      the GABA(A) receptor and the alpha1 subunit of the glycine receptor,
      respectively, were analyzed on midget and parasol cells in the marmoset (a New
      World monkey). Both GABA(A) and glycine receptors are distributed uniformly along
      the dendrites of ON and OFF types of parasol and midget ganglion cells,
      indicating that functional differences between these subtypes of ganglion cells
      are not determined by GABA or glycinergic input.

PMID- 10891878
TI  - Presynaptic proteins of ribbon synapses in the retina.
AB  - The synapses of photoreceptors and bipolar cells in the retina are characterized
      ultrastructurally by the presence of an electron-dense bar, the synaptic ribbon,
      lying perpendicular to the plasma membrane at the active zone and extending about
      0.5 microm into the cytoplasm. Hence, these synapses are known as ribbon
      synapses. All neurons that make ribbon synapses release neurotransmitter
      tonically. That is, neurotransmitter is released continuously from these neurons
      and the rate of release is modulated in response to graded changes in the
      membrane potential. This contrasts with action potential-driven, phasic release
      from other neurons. Similar to other synapses, neurotransmitter is released at
      ribbon synapses by the calcium-dependent exocytosis of synaptic vesicles. Most
      components of the molecular machinery governing transmitter release are conserved
      between ribbon and conventional synapses, but several differences that may be
      important determinants of tonic transmitter release have been identified in the
      retina by immunohistochemistry. For example, the presynaptic calcium channels of
      bipolar cells and photoreceptors are different from those elsewhere in the brain.
      Differences have also been found in the proteins involved in synaptic vesicle
      recruitment to the active zone and in synaptic vesicle fusion. These differences
      and others are discussed in terms of their implications for neurotransmitter
      release from photoreceptors and bipolar cells in the retina.

PMID- 10891879
TI  - Glial cells in the bird retina: immunochemical detection.
AB  - The avian retina is remarkably different from its mammalian counterpart in
      macroglial cell appearance. First, it is completely devoid of astrocytes. Thus,
      Muller cells constitute the only astrocytic-like cell population in avian
      retinae, whereas mammalian retinae also contain astrocytes in close association
      with blood vessels. Second, axons in the optic nerve layer of the retina of birds
      are myelinated, unlike those found in most mammalian species, with the exception
      of the rabbit, in which the medullary rays of the retina are myelinated by
      oligodendrocytes. Recent studies have revealed evidence that bird retinae contain
      a large number of oligodendrocytes, but which glial cell type myelinates axons
      intraretinally is still controversial. Apart from macroglial appearance,
      microglia in the bird retina show a very similar pattern of distribution to that
      of mammalian counterparts. This article reviews the existing data, including our
      new observations, and discusses the issues that remain to be resolved.

PMID- 10891880
TI  - SEM search for sound production and sound perception organs in a variety of
      Drosophila species.
AB  - The discovery of new song types in Hawaiian Drosophila species has raised a
      question of alternative sound production and sound perception mechanisms in
      Drosophila. For example D. disjuncta males, which produce song with a carrier
      frequency of 5,000-6,000 Hz, do not vibrate their wings but only tremble them in
      a very small amplitude while singing. In our SEM search we found at the wing base
      of the flies of this species a special structure which could play a part in song
      production. Our search for auditory sense organs in Drosophila species revealed
      that the aristae on fly antennae are structurally not as simple as has been
      assumed. In Hawaiian D. planitibia subgroup species, the fly aristae are more
      regular than in other Drosophila species and they are also covered with small
      hairs. We did not find any sign of tympanic hearing organs in any of the studied
      species, but we discovered on fly legs and wings sensilla which could play a part
      in sound/vibration perception. Our SEM survey provides a good starting point in
      the search for alternative pathways for sound production and perception via
      transmission electron microscopy combined with behavioral studies and
      electrophysiological recordings in Hawaiian Drosophila species.

PMID- 10891881
TI  - Distinct vascular zones in the canine prostate.
AB  - The vascular bed of canine prostate was studied and detailed distinct vascular
      zones were visualized on corrosion casts by scanning electron microscopy. This
      study was performed because of scarce information about the zonal vascularization
      of the prostate gland in dogs. There are no studies for three-dimensional
      microvascular distribution of the capsular vessels and the capsular microvascular
      trabeculae. SEM (vascular corrosion casting method) was used to show 3D
      angioarchitecture of the prostate gland. The lobules on the dorsal and lateral
      surface of the gland were numerous but small. Their small size is probably due to
      the abundant blood supply in the region. Few but large ventral lobules were
      observed. Three prostatic zones were clearly defined: capsular, parenchyma, and
      urethral. The diameter of the venous blood vessel compared to arterial vessels of
      the capsule was smaller. Two types of arteries were observed in trabeculae:
      direct and branched. The direct arteries were straight, with only a few branches.
      The branched arteries contained many bifurcations, with the vessel's diameter
      decreasing gradually. The trabeculae capillary network formed loops, with
      frequent sphincter-like constrictions and pouch-like protuberances.

PMID- 10891882
TI  - X-ray microanalysis of intestinal chloride transport in vitro and in vivo.
AB  - Chloride secretion from crypt cells in mouse duodenum or jejunum was investigated
      in in vivo and in vitro models by electron probe X-ray microanalysis. IBMX
      induced chloride secretion could not be demonstrated in vivo, presumably because
      of competing systemic effects. However, chloride secretion could be induced by
      300 microM IBMX in vitro. The best results were obtained under the following
      conditions: a long preincubation of the tissue slices in high potassium or saline
      buffer (preferably in high potassium buffer), oxygenated with 95% O(2) and 5%
      CO(2), at low temperature (4 degrees C), followed by IBMX stimulation in saline
      buffer at 37 degrees C. Chloride efflux was accompanied by efflux of Na and K.

PMID- 10891883
TI  - TNFalpha in the millennium twilight

PMID- 10891884
TI  - TNF alpha and the TNF receptor superfamily: structure-function relationship(s).
AB  - Tumour Necrosis Factor alpha (TNF alpha), is an inflammatory cytokine produced by
      macrophages/monocytes during acute inflammation and is responsible for a diverse
      range of signalling events within cells, leading to necrosis or apoptosis. The
      protein is also important for resistance to infection and cancers. TNF alpha
      exerts many of its effects by binding, as a trimer, to either a 55 kDa cell
      membrane receptor termed TNFR-1 or a 75 kDa cell membrane receptor termed TNFR-2.
      Both these receptors belong to the so-called TNF receptor superfamily. The
      superfamily includes FAS, CD40, CD27, and RANK. The defining trait of these
      receptors is an extra cellular domain comprised of two to six repeats of cysteine
      rich motifs. Additionally, a number of structurally related "decoy receptors"
      exist that act to sequester TNF molecules, thereby rescuing cells from apoptosis.
      The crystal structures of TNF alpha, TNF beta, the extracellular domain of TNFR-1
      (denoted sTNFR-1), and the TNF beta sTNFR-1 complex have been defined by
      crystallography. This article will review the structure/function relationships of
      the TNF alpha and the TNF receptor superfamily. It will also discuss insights as
      to how structural features play a role in the pleiotropic effects of TNF alpha.

PMID- 10891885
TI  - Role of TNF in lymphocyte-mediated cytotoxicity.
AB  - We now know that tumor necrosis factor (TNF) family ligands regulate development
      of lymphoid tissue and coordinate cellular differentiation to defend against
      intracellular pathogens. In particular, TNF provides essential signals for the
      formation of secondary lymphoid tissue structures and plays an important role in
      several physiological and pathological conditions that relate to its action in
      inflammation and leukocyte movement. The TNF-related family of membrane-anchored
      and secreted ligands also represents a major mechanism regulating cell death and
      cell survival. TNF was first described as an endotoxin-induced and macrophage
      secreted factor that caused haemorrhagic necrosis of tumor cells. Over the past
      two decades we have come to appreciate that T lymphocytes and natural killer (NK)
      cells also produce TNF, yet no clear single role for lymphocyte-derived TNF has
      emerged. This review describes the key molecular details of the action of TNF and
      discusses the evidence for TNF-mediated cytotoxicity being critical to lymphocyte
      function and immunoregulation.

PMID- 10891886
TI  - Tumor necrosis factor-alpha regulates secretion of the adipocyte-derived
      cytokine, leptin.
AB  - The seminal observation that secretion of the adipocyte-derived hormone leptin
      was induced by inflammatory challenge has been expanded upon to demonstrate the
      importance of the pro-inflammatory cytokines, especially tumor necrosis factor
      (TNF)-alpha, in inflammatory hyperleptinemia. Initially, it was thought that
      cytokine-induced hyperleptinemia might somehow be involved in the anorexia and
      cachexia that often accompany chronic infectious, neoplastic, and autoimmune
      disease. While the role of leptin in disease-associated anorexia and cachexia
      appears tenuous in light of recent findings, there is evidence that the
      hyperleptinemia induced by cytokines is an integral part of the acute phase
      response and necessary for comprehensive immunocompetence. This hints at the
      existence of an integrated communication network, wherein the energy status of
      the animal impacts its ability to fight pathogens.

PMID- 10891887
TI  - TNF-alpha gene polymorphism: clinical and biological implications.
AB  - TNF-alpha is a proinflammatory cytokine that has been implicated in the severity
      of different immune-regulated diseases including autoimmune diseases and
      transplantation. The gene for TNF-alpha is located within the MHC region on
      chromosome 6p21.3. This is a highly polymorphic region, and the TNF-alpha itself
      contains a large number of polymorphisms. Some of these polymorphisms form
      extended haplotypes with the HLA class I and II alleles. TNF polymorphisms have
      been investigated in different diseases and most often whenever there is an HLA
      association with the disease (for example IDDM and RA) association(s) with TNF
      polymorphisms has been described. There are many studies on the function of the
      TNF polymorphisms showing the influence of the different alleles on the in vitro
      and in vivo levels of TNF production. However, recent studies in animal models
      suggest that not only polymorphisms within the TNF cluster are important in the
      regulation of TNF production but also the receptors as well (TNF R). This
      suggests that investigating polymorphisms within the TNF cluster and TNF
      receptors will be important in understanding the role of TNF regulation in a
      given disease.

PMID- 10891888
TI  - Anti-TNF therapies in rheumatoid arthritis, Crohn's disease, sepsis, and
      myelodysplastic syndromes.
AB  - An attempt has been made in this article to summarize the state-of-the-art
      clinical experience with the use of anti-TNF therapies in four diseased states
      with special emphasis on myelodysplastic syndromes. Given the central role of TNF
      alpha in initiating and perpetuating the chronic damage produced in the diseased
      organs by controlling a cascade of pro-inflammatory cytokines, as well as its
      acute role in sepsis, theoretically speaking, neutralization of this peptide was
      a natural therapeutic choice. Results of the initial clinical trials appear
      encouraging and sometimes dramatic in their efficacy. The mechanism of response
      however, is interesting in that even when TNF-alpha is directly targeted by a
      monoclonal antibody, the resulting benefits can frequently not be attributed to
      TNF suppression alone. Rather, it appears that a more general effect on the T
      lymphocytes is also contributing to the responses being seen. This raises the new
      possibility of combining anti-cytokine and anti-T-cell strategies to treat at
      least the more chronic diseases such as Crohn's disease and myelodysplastic
      syndromes. Continued clinical trials testing these strategies are clearly
      warranted.

PMID- 10891889
TI  - Tumor necrosis factor-alpha induced DNA cleavage in human articular chondrocytes
      may involve multiple endonucleolytic activities during apoptosis.
AB  - Apoptosis has been documented in chondrocytes both in the growth plates of young,
      healthy cartilages and in osteoarthritic cartilages; little, however, is known
      about apoptosis in chondrocytes of normal adult articular cartilage. For the
      current study, apoptosis in adult chondrocytes was evaluated by labeling DNA
      fragments using the ISEL in situ end labeling of 3'-recessed strand breaks) or
      TUNEL (5'-recessed or blunt-ended strand breaks with terminal deoxynucleotidyl
      transferase-mediated nick end labeling) techniques in primary cultures of
      chondrocytes in monolayer. Apoptosis was induced in the chondrocytes by either
      Tumor Necrosis Factor alpha (TNF alpha), Interleukin 1-beta (IL-1 beta), or anti
      Fas antibody but only after 48 hours in culture. At 4 and 24 hours, there was no
      detectable DNA fragmentation. With TNF alpha, IL1 beta, and anti-Fas antibody,
      chondrocytes show evidence of at least two types of DNA strand breaks within the
      same cell (as assessed by simultaneous labeling with ISEL and TUNEL). Therefore,
      some pathways leading to apoptosis in chondrocytes appear to involve more than
      one type of endonuclease activity. When the chondrocytes were cultured as
      explants with the articular matrix intact (ex vivo), neither IL-1 beta, TNF
      alpha, the anti-Fas antibody, nor fibronectin fragments were able to induce
      apoptosis in the chondrocytes. In normal human adult cartilage that was untreated
      and uncultured (in situ), DNA fragmentation was undetectable; however, a
      significant number of chondrocytes in osteoarthritic cartilage did contain strand
      breaks. These data suggest that apoptosis occurs in chondrocytes in which the
      matrix has been disrupted experimentally or destroyed by the osteoarthritic
      disease process. The results of these studies suggest that the ECM may be an
      essential survival factor for chondrocytes.

PMID- 10891890
TI  - Detection of membrane-bound tumor necrosis factor (TNF): an analysis of TNF
      specific reagents.
AB  - Tumor necrosis factor (TNF) exists in two bioactive forms, the membrane
      integrated form and the proteolytically derived soluble cytokine. Both forms of
      TNF are involved in a variety of different physiological and pathophysiological
      situations. Here we analyzed different human and mouse TNF-specific reagents for
      their ability to determine the expression of membrane-expressed TNF. The data
      prove some antibodies to be very useful for the analysis of transmembrane TNF
      expression because these antibodies distinguish between the transmembrane form of
      TNF and soluble TNF bound to cellular TNF receptors. In addition, we found that
      recombinant human TNF receptor fusion proteins are advantageous tools to analyze
      both human and mouse transmembrane TNF expression.

PMID- 10891891
TI  - Tumor necrosis factor modulates CD 20 expression on cells from chronic
      lymphocytic leukemia: a new role for TNF alpha?
AB  - Tumor necrosis factor alpha (TNF alpha) is a pleiotropic cytokine that is
      constitutively produced by leukemic cells in B Chronic Lymphocytic Leukemia (B
      CLL). It has been shown to have autocrine and paracrine functions in normal B
      cells and in B lymphoproliferative diseases. This study was conducted to
      determine the effect of TNF alpha (in vitro) on CD20 expression on cells from
      patients with B-CLL. Currently, anti-CD20 monoclonal antibody therapy is becoming
      a second line treatment in the management of B cell disorders like low-grade non
      Hodgkin's lymphoma (NHL) and B-CLL. Our results demonstrate amply that very low
      doses of TNF alpha (0. 0125 ng/ml) can be used to significantly increase CD20
      expression on cells from patients of B-CLL as evidenced by increases in both
      percentage positivity and mean fluorescence intensity. The upregulation is
      evident as early as 24 hours and is maintained for up to 72 hours. We propose
      that the upregulation is a direct result of in vitro differentiation stimulated
      by TNF alpha. The results presented can be exploited in the designing of priming
      protocols prior to antibody therapy and this is discussed.

PMID- 10891893
TI  - Neurology: A journal for authors and readers.

PMID- 10891894
TI  - Treatment of myasthenia gravis: A call to arms.

PMID- 10891895
TI  - Emerging concepts in the pathophysiology of recovery from neonatal brachial
      plexus injury.

PMID- 10891896
TI  - Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence
      based review): report of the Quality Standards Subcommittee of the American
      Academy of Neurology.

PMID- 10891897
TI  - Myasthenia gravis: recommendations for clinical research standards. Task Force of
      the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of
      America.

PMID- 10891899
TI  - Low mini-mental status predicts mortality in asymptomatic carotid arterial
      stenosis. Asymptomatic Carotid Atherosclerosis Study investigators.
AB  - OBJECTIVE: To determine whether carotid endarterectomy is superior to best
      medical therapy in preserving cognition, and whether low Mini-Mental State
      Examination (MMSE) scores predict TIA, stroke, myocardial infarction, or death.
      METHODS: Subjects participating in the Asymptomatic Carotid Atherosclerosis Study
      were administered the MMSE at periodic intervals. Group means were calculated at
      randomization, 1 and 3 months later, and every 6 months thereafter. The group
      means were compared by treatment and over time. A proportional hazard regression
      model incorporating postrandomization MMSE score as a predictor variable was used
      to estimate risk of death, stroke, or other outcome events. RESULTS: There was no
      intergroup difference in mean MMSE score during 5 years of observation. For
      individual patients, the relationship between a low postrandomization score on
      the MMSE and increased risk of death was significant (p </= 0.0001). Patients who
      experienced stroke after randomization also had a significant and persistent
      reduction in MMSE score (p </= 0.0001). CONCLUSIONS: Carotid endarterectomy had
      no impact on MMSE score in this study. Patients with low postrandomization MMSE
      scores had a greater likelihood of death. Stroke reduced MMSE scores and may
      portend cognitive impairment. The authors recommend the routine inclusion of
      cognitive testing in future clinical trials designed to evaluate prophylaxis or
      acute therapy of stroke.

PMID- 10891898
TI  - Developmental apraxia arising from neonatal brachial plexus palsy.
AB  - OBJECTIVE: To determine whether motor unit activation is impaired in patients
      with persisting disability arising from neonatal brachial plexus palsy (NBPP).
      BACKGROUND: In NBPP patients, the authors previously found more extensive muscle
      reinnervation than might have been anticipated from the clinical examination.
      METHODS: Motor skills were tested in a group of nine boys and seven girls with
      prior NBPP, who then underwent physiologic investigation of proximal and distal
      muscles in their affected and unaffected arms. The latter tests comprised
      measurements of maximal evoked muscle compound action potential (M-wave)
      amplitude, maximal voluntary torque, twitch torque, and twitch interpolation. A
      group of 17 children of similar ages served as control subjects. RESULTS: In the
      NBPP group, motor skills were diminished and voluntary torque was reduced
      relative to M-wave amplitude and twitch torque. Moreover, interpolated twitches
      could be demonstrated in some NBPP patients but not in control subjects.
      CONCLUSION: Persisting disability in NBPP patients is due, at least in part, to
      impaired motor unit activation. The authors suggest that the impairment is a form
      of developmental apraxia caused by defective motor programming in early infancy.

PMID- 10891900
TI  - Access www.neurology.org now for full-text articles

PMID- 10891901
TI  - Correlation of cerebral hemodynamic changes during mental activity and recovery
      after stroke.
AB  - OBJECTIVE: To investigate the correlation between changes in cerebral functional
      activity during mental engagement and the potential for neurologic recovery after
      stroke. BACKGROUND: Transcranial Doppler ultrasonography (TCD) makes it possible
      to detect the dynamic adjustment of cerebral perfusion related to functional
      neuronal changes. METHODS: TCD monitoring of flow velocity changes in the middle
      cerebral artery of 29 ischemic stroke patients was performed during an object
      recognition task. The study took place within 4 weeks from stroke onset. Based on
      recovery occurring after 2 months, the patients were divided into four groups
      depending on the side of hemispheric lesion and the presence or absence of
      neurologic recovery. Ten healthy subjects served as control subjects. RESULTS:
      During the recognition task, control subjects showed a bilateral increase in flow
      velocity with respect to the rest phase (right side, 7.02 +/- 1.3%; left side,
      6.65 +/- 1. 1%), with no side-to-side difference. In patients who experienced
      recovery, a similar pattern of bilateral activation was observed, irrespective of
      the side of the lesion. Conversely, in patients with no recovery, the increase of
      flow velocity was significantly higher on the side contralateral to the brain
      lesion (p < 0.0001) with respect to the lesion side. Performance during the
      recognition task was comparable in the four groups of patients. CONCLUSIONS:
      These findings suggest that satisfactory recovery from a neurologic deficit
      requires the persistence of functional activity in the damaged hemisphere despite
      the presence of an anatomic lesion. The possibility of obtaining early prognostic
      indications with TCD may be relevant for an early selection of patients with the
      best probability of benefiting from rehabilitation therapy.

PMID- 10891903
TI  - Activate your online subscription

PMID- 10891902
TI  - Visual function loss from vigabatrin: effect of stopping the drug.
AB  - OBJECTIVE: To determine if visual function loss from vigabatrin use recovers
      after the drug is discontinued. BACKGROUND: Vigabatrin is an effective
      antiepileptic drug, but it is known to cause a variety of changes in visual
      function, including reductions in the visual field, visual acuity, color vision,
      and in electroretinogram (ERG) and electro-oculogram amplitudes. It is not known
      whether these changes are reversible. METHODS: Measurements of static and kinetic
      visual fields, visual acuity, color vision, and the ERG were recorded while
      patients were taking vigabatrin and again in 13 patients who had discontinued the
      drug because of lack of efficacy or reductions in visual field. Most of the
      patients had been off the drug for 3 to 6 months, although two patients had been
      drug-free for almost 1 year. RESULTS: Although ERG cone implicit time improved,
      most of the patients did not show improvement in either clinical measures of
      visual function (i.e., visual acuity, color vision, visual fields) or in ERG
      amplitudes. However, several patients who showed minimal visual field loss while
      on the drug had substantial recovery of ERG amplitudes. There was no statistical
      association between recovery of function and either duration of treatment or
      cumulative dosage. The multifocal ERG showed a diffuse loss of function that was
      not isolated to the periphery. CONCLUSIONS: Although the visual deficits in
      patients taking vigabatrin tend to be mild, most patients do not show improvement
      after they stop taking the drug. Visual field loss resulting from vigabatrin was
      not reversible. Visual acuity, color vision, and ERG amplitude loss may be
      reversible in patients with minimal or no field loss.

PMID- 10891904
TI  - Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant
      epilepsy.
AB  - BACKGROUND: Autoantibodies to glutamic acid decarboxylase (GAD-A) are present in
      type 1 diabetes and stiff man syndrome (SMS), and have also been reported in
      cerebellar ataxia. Epilepsy was present in 4 of 19 patients with SMS and GAD-A,
      implying that epilepsy sometimes is associated with anti-GAD autoimmunity.
      METHODS: The authors investigated the prevalence of GAD-A in patients with
      therapy-resistant localization-related epilepsy (n = 51) and generalized epilepsy
      (n = 49) by a radiobinding assay. The positive samples were confirmed by
      immunohistochemistry and immunoblotting of recombinant human GAD65. RESULTS: GAD
      A were found in eight patients with localization-related epilepsy, whereas none
      of the patients with generalized epilepsy, other neurologic disorders (n = 38),
      or the control subjects (n = 48) had GAD-A. Two patients had high levels of GAD
      A, similar to SMS, whereas six patients had significantly lower titers,
      characteristic of type 1 diabetes. The two patients with high levels of GAD-A had
      GAD-A both in serum and CSF by immunohistochemistry and immunoblotting. Both of
      them had longstanding therapy-resistant temporal lobe epilepsy but did not have
      diabetes. One had a history of autoimmune disease, whereas the other had
      serologic evidence of multiple autoantibodies without any clinical signs of
      autoimmune disease. CONCLUSIONS: GAD autoimmunity may be associated with
      refractory localization-related epilepsy.

PMID- 10891905
TI  - Quality of life as a predictor for change in disability in MS.
AB  - OBJECTIVE: To investigate the predictive value of quality of life on changes in
      disability measured by the Expanded Disability Status Scale (EDSS). BACKGROUND:
      There are few good prognostic factors for disease development in MS. Quality of
      life and self-rated health have been shown to be highly predictive of morbidity
      and disease development in heart disease and cancer. METHODS: Data on quality of
      life (SF-36 Health Survey) were ascertained at baseline for 97 relapsing
      remitting patients with MS participating in a short-term clinical trial on
      interferon alpha-2a. These scores were correlated with change in EDSS scores 1
      year later, 6 months after treatment ended. RESULTS: Low scores on the SF-36
      mental health scale were correlated with increased (worsened) EDSS scores 1 year
      later (r = -0.29, p = 0.006). The results were not altered by adjusting for
      disease activity at baseline, which was measured by the number gadolinium
      enhanced MRI lesions, relapse rate for the preceding 2 years, and baseline EDSS
      score. Similar results were found for self-rated health (according to the first
      question of the SF-36). CONCLUSIONS: These findings reinforce the importance of
      incorporating the patients' evaluation of their quality of life during treatment.
      Further, assessing such measures is important in evaluating effects in treatment
      trials in MS.

PMID- 10891906
TI  - Psychological stress and the subsequent appearance of new brain MRI lesions in
      MS.
AB  - OBJECTIVE: To examine the relationship between stressful life events and
      psychological distress, and the subsequent development of gadolinium-enhancing
      (Gd+) brain lesions. BACKGROUND: It has long been speculated that stressful life
      events and psychological distress are associated with disease exacerbation in MS.
      This is the first prospective longitudinal study of the relationship between
      stressful life events, psychological distress, and disease activity as measured
      by Gd+ brain MRI. METHODS: Thirty-six patients (mean age, 44.4 years; 22 women,
      14 men) with relapsing forms of MS were assessed once every 4 weeks for 28 to 100
      weeks. Assessments included Gd+ MRI, the Social Readjustment Rating Scale (SRRS),
      the Hassles Scale, and the Profile of Mood States. The SRRS was altered in the
      following manner: 1) three items that confounded with MS were eliminated, 2)
      endorsed items were rated for intensity, and 3) the scale was divided into three
      subscales: major negative events, conflict and disruption in routine, and
      positive life events. Data were analyzed using mixed-effects logistic regression
      to account for intrasubject correlations. Stress and distress measures were used
      to predict concurrent and future MRI activity. RESULTS: For the total sample of
      patients, increased conflict and disruption in routine was followed by increased
      odds of developing new Gd+ brain lesions 8 weeks later (odds ratio, 1.64; p =
      0.00083). There was no strong evidence of a relationship between psychological
      stress or distress and clinical exacerbation. CONCLUSIONS: These data provide
      support for the notion that conflict and disruption in routine are related to
      subsequent disease activity in MS. However, this relationship is not sufficiently
      robust to predict clinical exacerbations reliably in individual patients.

PMID- 10891908
TI  - The incidence of dementia in Canada. The Canadian Study of Health and Aging
      Working Group.
AB  - OBJECTIVE: To estimate the incidence of dementia, including AD, among Canadians
      aged 65 and over. METHODS: A 5-year cohort study of 10,263 seniors was
      undertaken, including community and institutional samples. The baseline study in
      1991 identified 1,132 prevalent cases of dementia through screening and clinical
      examination. The remaining 9,131 cases formed the incidence study sample and were
      rescreened and selectively reexamined in 1996. Incident cases were diagnosed
      using established criteria. Incidence was estimated based on the 1991 population,
      and included data on those who died between the first and second phases of the
      study. RESULTS: Of the nondemented cohort who remained alive in 1996, 5,432
      people in the community (88.3%) and 210 (91.3%) in the institutional sample
      participated in the incidence study. Nine hundred sixty incident cases were
      identified; the overall age-standardized incidence rates were 21.8 (women) and
      19.1 (men) per 1,000 nondemented persons per year. This translates into 60,150
      new cases of dementia per year in Canada. The logarithm of the rates rises
      linearly with age, but suggests a slight slowing of growth in incidence in the
      oldest age groups. CONCLUSIONS: Our incidence estimates lie toward the upper end
      of the range of incidence estimates found in other studies. Nonetheless, we
      calculate that several factors may have biased our estimates downward, suggesting
      that the incidence of dementia may be higher than many studies have reported.

PMID- 10891907
TI  - The effect of gadolinium-enhancing lesions on whole brain atrophy in relapsing
      remitting MS.
AB  - OBJECTIVE: To determine the relationship between gadolinium-enhancing lesions and
      changes in whole brain parenchymal volume in patients with relapsing-remitting
      MS, and to test the hypothesis that gadolinium enhancement is a predictor of
      whole brain atrophy. METHODS: Twenty-four patients with clinically definite MS
      were imaged over 2 years. A computer-assisted segmentation technique based on
      high-resolution MRI was used to quantify gadolinium-enhancing T1 lesion volume
      and brain parenchyma and CSF volumes. Percent brain parenchymal volume (PBV)
      relative to the total intracranial volume was calculated, and changes in PBV were
      used to represent the degree of whole brain atrophy over 2 years. RESULTS: PBV at
      baseline was dependent on duration of MS, and a significant decrease in PBV was
      observed over the course of the study. Changes in enhanced T1 lesion load failed
      to correlate with changes in PBV, and multiple regression analyses determined
      that enhanced T1 lesion load at baseline was not a significant predictor of
      subsequent change in PBV. CONCLUSIONS: MR visible inflammation as demonstrated by
      enhanced T1 lesions is not a significant factor in the pathogenesis of whole
      brain atrophy in relapsing-remitting MS, suggesting that a more global pathologic
      process is responsible for the loss of brain parenchymal volume.

PMID- 10891909
TI  - Recovery from spontaneous confabulations parallels recovery of temporal confusion
      in memory.
AB  - BACKGROUND: In previous studies, the authors found that patients with spontaneous
      confabulation differ from those with nonconfabulating amnesia by 1) temporal
      context confusion (TCC) in memory based on an inability to suppress intrusions of
      currently irrelevant memory traces into ongoing thinking; and 2) lesions
      involving the orbitofrontal cortex, basal forebrain, or amygdala and perirhinal
      cortex. OBJECTIVES: To study the long-term clinical course of spontaneous
      confabulations, determine whether TCC in memory also parallels the clinical
      course of spontaneous confabulations, and study the impact of lesion site on
      clinical course. METHODS: Eight patients with spontaneous confabulation were re
      examined 18 months after onset. Tests of memory and executive functioning and
      measurement of TCC in memory were again applied. MRI according to a standard
      protocol was performed to determine areas of permanent damage. RESULTS: Seven
      patients eventually stopped confabulating. TCC, but not common memory or
      executive tests, precisely paralleled the course of spontaneous confabulations.
      Patients with isolated, less extensive, orbitofrontal lesions stopped
      confabulating first and had the best neuropsychological outcome. Patients with
      basal forebrain lesions continued to confabulate for several months and remained
      amnesic. One patient with extensive orbitofrontal damage and perirhinal cortex
      damage continues to confabulate after more than 3 years, continuing to confuse
      memory traces. CONCLUSIONS: Temporal context confusion in memory is not only the
      sole feature reliably separating patients with spontaneous confabulation from
      those with nonconfabulating amnesia in the acute stage, it is also the only
      feature that precisely parallels the clinical course of spontaneous
      confabulations. Most patients eventually stop confabulating but duration of
      confabulations depends on the lesion site.

PMID- 10891910
TI  - Distinctive pathologic findings in proximal diabetic neuropathy (diabetic
      amyotrophy).
AB  - OBJECTIVE: To investigate the pathogenesis of proximal diabetic neuropathy (PDN)
      with nerve and muscle biopsies. BACKGROUND: Recent evidence suggests that nerve
      ischemia secondary to immune-mediated vasculopathy rather than diabetic
      microangiopathy may be responsible for PDN. METHOD: - Fifteen patients with PDN
      and two diabetic controls underwent nerve and muscle biopsy and clinical,
      electrophysiologic, and laboratory evaluation. There were eight men and seven
      women between 49 and 79 years of age with type II diabetes. All had progressive,
      painful, asymmetric, proximal weakness with duration of 5 weeks to 12 months.
      None had evidence of systemic autoimmune disorder. RESULTS: Four patients showed
      the distinctive findings of polymorphonuclear small-vessel vasculitis affecting
      epineurial vessels with transmural infiltration of postcapillary venules with
      polymorphonuclear leukocytes. Immunoglobulin M (IgM) deposits were found along
      the endothelium and intramurally in affected vessels. IgM staining was seen in
      the subperineurial space and in the endoneurium. Activated complement deposition
      was seen along endothelium of small vessels. Three of these four patients were
      evaluated within 6 seeks of onset of PDN, and the fourth patient during acute
      flare of PDN 6 months after the initial onset. Six patients showed
      "perivasculitis" with mononuclear cell infiltrates around small epineurial
      vessels without vasculitis (fibrinoid necrosis or transmural inflammation). One
      patient showed recanalized vessels with transmural lymphocytes without fibrinoid
      necrosis, possibly suggesting healed vasculitis. CONCLUSION: These distinctive
      pathologic findings support that proximal diabetic neuropathy has an immune
      mediated inflammatory basis and suggest that polymorphonuclear vasculitis with
      immune complex and complement deposition may be the primary event in the acute
      phase of proximal diabetic neuropathy.

PMID- 10891911
TI  - Clinical and pathologic findings in hereditary spastic paraparesis with spastin
      mutation.
AB  - OBJECTIVE: To describe a family with chromosome 2p-linked hereditary spastic
      paraparesis (HSP) associated with dementia and illustrate the cerebral pathology
      associated with this disorder. BACKGROUND: HSP comprises a heterogeneous group of
      inherited disorders in which the main clinical feature is severe, progressive
      lower limb spasticity. Nongenetic classification relies on characteristics such
      as mode of inheritance, age at onset, and the presence or absence of additional
      neurologic features. Several loci have been identified for autosomal dominant
      pure HSP. The most common form, which links to chromosome 2p (SPG4), has recently
      been shown to be due to mutations in spastin, the gene encoding a novel AAA
      containing protein. RESULTS: The authors report four generations of a British
      family with autosomal dominant HSP in whom haplotype analysis indicates linkage
      to chromosome 2p. In addition, a missense mutation has been identified in exon 10
      of the spastin gene (A1395G). Dementia was documented clinically in one member of
      the family, two other affected family members were reported to have had late
      onset memory loss, and a younger affected individual showed evidence of memory
      disturbance and learning difficulties. Autopsy of the demented patient confirmed
      changes in the spinal cord typical of HSP and also demonstrated specific cortical
      pathology. There was neuronal depletion and tau-immunoreactive neurofibrillary
      tangles in the hippocampus and tau-immunoreactive balloon cells were seen in the
      limbic and neocortex. The substantia nigra showed Lewy body formation. The
      pathologic findings are not typical of known tauopathies. CONCLUSIONS: The
      authors confirm that chromosome 2p-linked HSP can be associated with dementia and
      that this phenotype may be associated with a specific and unusual cortical
      pathology.

PMID- 10891912
TI  - Effect of naratriptan on myocardial blood flow and coronary vasodilator reserve
      in migraineurs.
AB  - BACKGROUND: Migraine drugs can produce adverse cardiac effects. The authors have
      demonstrated previously that ergotamine can lead to a significant reduction of
      hyperemic myocardial blood flow, but little is known about the effect of the
      newer serotonin analogues. Coronary artery constriction caused by serotonin or
      its analogues is mediated mainly by 5HT2 receptors. The selective 5HT1B/1D
      agonist naratriptan has no significant activity at 5HT2 receptors; however, like
      all 5HT1B/1D agonists developed for the acute treatment of migraine, naratriptan
      could potentially constrict coronary arteries by activation of 5HT1B receptors.
      METHODS: The effects on myocardial blood flow of subcutaneous naratriptan 1.5 mg
      compared with placebo were assessed under resting and hyperemic conditions with
      PET using oxygen-15 labeled water during two separate visits. This study was a
      randomized, double-blind, placebo-controlled crossover trial in 34 migraine
      subjects with no evidence of ischemic heart disease, studied outside a migraine
      attack. RESULTS: Naratriptan did not differ significantly from placebo in its
      effects on resting myocardial blood flow, but did evoke a small, significant fall
      in hyperemic myocardial blood flow (-13% versus placebo) and an increase in
      hyperemic coronary resistance (+19% versus placebo) without any signs or symptoms
      suggestive of myocardial ischemia. Naratriptan did not significantly affect the
      coronary vasodilator reserve (hyperemic/resting blood flow) compared with
      placebo. CONCLUSIONS: These results show that at therapeutic doses, naratriptan
      exerts only a minor effect on myocardial blood flow, coronary vasodilator
      reserve, or coronary resistance among subjects with no evidence of ischemic heart
      disease. These results should not be extrapolated to patients with coronary
      artery disease, in whom all 5HT1 agonists for migraine are contraindicated.

PMID- 10891913
TI  - Central and peripheral nervous system dysfunction in the clinical variation of
      Salla disease.
AB  - OBJECTIVE: To evaluate the degree of possible peripheral nervous system (PNS)
      involvement in addition to CNS manifestations in Salla disease, a free sialic
      acid storage disorder leading to severe mental retardation with a wide clinical
      variation. BACKGROUND: Salla disease is a lysosomal storage disorder that affects
      the white matter of the CNS. MRI findings and recent 1H MRS study results provide
      evidence for delayed central myelination, but there is no previous evidence for
      PNS involvement in this disease. The gene coding for a presumptive sialic acid
      transport protein has recently been identified, and the first disease-causing
      mutations have been characterized. METHODS: Nerve conduction studies; evoked
      potentials to visual (VEP), brainstem auditory (BAEP), and somatosensory stimuli
      (SEP); and EEG were carried out on 22 patients (age range 2 months to 57 years)
      with biochemically and genetically confirmed Salla disease. Brain MRI were
      available on 14 patients. RESULTS: Nerve conduction studies revealed
      abnormalities in nearly half of the patients (10/21). The four severely disabled
      patients and the oldest patient had greatly reduced nerve conduction velocities
      and prolonged distal latencies compatible with demyelinating polyneuropathy. In
      addition, SEP was abnormal in the majority of the patients, but VEP and BAEP in
      only a few cases. PNS involvement was clearly associated with both the phenotypic
      severity and MRI findings. CONCLUSIONS: The results indicate that dysmyelination
      in Salla disease occurs not only in the CNS but also in the peripheral nervous
      system, contributing to the phenotypic variation, which can now be correlated
      with the molecular basis of the disease.

PMID- 10891914
TI  - Blood-brain barrier function in cerebral malaria and CNS infections in Vietnam.
AB  - BACKGROUND: The intraerythrocytic parasite Plasmodium falciparum induces the life
      threatening neurologic syndrome of cerebral malaria (CM) from within cerebral
      blood vessels, without entering the brain parenchyma. OBJECTIVES: 1) To assess
      the use of CSF as an indicator of specific pathologic processes occurring in the
      brain during CM; 2) to compare this with other neurologic and infectious diseases
      to understand the distinct pathogenic features of CM; 3) to test the hypothesis
      that CM involves a specific functional breakdown of the blood-brain barrier
      (BBB). METHODS: 1) Radial immunodiffusion assays to detect albumin and IgG in
      matched plasma and CSF samples as indicators of BBB integrity and intrathecal IgG
      production; and 2) ELISA for soluble intracellular adhesion molecule-1 and sE
      selectin, the cytokines tumor necrosis factor-alpha and transforming growth
      factor-beta1, and the matrix metalloproteinase MMP-9, to detect cellular
      activation and inflammatory responses within the brain. RESULTS: Albumin and IgG
      indices implied only minimal degree of BBB breakdown in a few cases of CM, with
      most remaining within the normal range. In contrast, cryptococcal, tubercular,
      and acute bacterial meningitis produced detectable changes in the composition of
      the CSF and evidence of BBB breakdown. CONCLUSIONS: CM appears to involve only
      subtle functional changes in BBB integrity with minimal intraparenchymal
      inflammatory responses compared with other neurologic infections. This focuses
      attention on local events within and around the cerebral microvasculature in CM,
      rather than indicating widespread parenchymal disease.

PMID- 10891915
TI  - Recurrent silent cerebral embolism.

PMID- 10891916
TI  - Botulinum toxin treatment of cocontractions after birth-related brachial plexus
      lesions.
AB  - The authors studied botulinum toxin type A therapy of severe biceps-triceps
      cocontractions after nerve regeneration following birth-related brachial plexus
      lesions. Six children (age, 2 to 4 years) were treated two to three times over a
      period of 8 to 12 months with 40 mouse units of botulinum toxin at two sites of
      the triceps muscle. Elbow range of motion improved from 0 to 25 to 50 deg to 0 to
      25 to 100 deg (p < 0.05), and muscle force of elbow flexion increased from a mean
      of Medical Research Council classification 1.7 to 3.7 (p < 0.05). After a 1-year
      follow-up, there was no clinical recurrence.

PMID- 10891917
TI  - Deep brain stimulation of subthalamic area for severe proximal tremor.
AB  - Proximal tremors are often refractory to nucleus ventrointermedius thalami
      thalamotomy. Subthalamotomy has been suggested to be effective for treatment of
      tremor, although this procedure is associated with considerable adverse effects,
      and has rarely been considered a suitable treatment modality. The authors
      demonstrate the efficacy and safety of subthalamic deep brain stimulation in two
      patients, one with a severe, refractory proximal essential tremor and one with
      tremor with dystonia.

PMID- 10891918
TI  - Response of leptomeningeal metastases from breast cancer to hormonal therapy.
AB  - Intraventricular chemotherapy with radiotherapy is the standard treatment of
      leptomeningeal metastasis (LM) from breast cancer; this treatment increases
      median survival only to about 3 months and is frequently complicated by serious
      side effects. The authors describe two patients with LM from breast cancer who
      were treated with hormonal therapy, which provided a neurologic response of at
      least 12 months and a survival of 14+ and 19 months. Hormonal therapy can be
      effective and nontoxic for patients with LM from breast cancer.

PMID- 10891919
TI  - Nonepileptic seizures in pregnancy.
AB  - The authors report five patients with recurrent psychogenic seizures (PS) during
      pregnancy, with multiple emergency room visits and continued intake of
      antiepileptic drugs obtained from various sources, despite awareness of the
      psychogenic nature of their attacks and the risks of antiepileptic drug use in
      pregnancy. These patients demonstrate that preexisting PS may persist during
      pregnancy, and there will be patients who continue to take antiepileptic drugs
      despite awareness of the risks inherent to these treatments. New-onset or
      persisting PS with pregnancy can be indicative of serious emotional conflicts,
      and the child should be considered at risk.

PMID- 10891920
TI  - Ictal SPECT during autonomic crisis in familial dysautonomia.
AB  - The authors report results of SPECT cerebral perfusion studies in two patients
      with familial dysautonomia (FD) during dysautonomic crises and when clinically
      stable. SPECT imaging studies used 99mTc ethylene cysteine dimer. During
      dysautonomic crises, regions in the temporoparietal and frontal lobes had
      increased uptake. Uptake in these areas was less during asymptomatic periods.
      Episodic asymmetric cerebral perfusion during crises especially affecting the
      frontal and temporal lobes is suggestive of ictal activity.

PMID- 10891921
TI  - Cutaneous innervation in hereditary sensory and autonomic neuropathy type IV.
AB  - The authors investigated immunocytochemically the innervation of a skin biopsy in
      a rare case of hereditary sensory and autonomic neuropathy type IV. A few protein
      gene product 9.5-, growth-associated protein 43-, calcitonin gene-related peptide
      , and substance P-immunoreactive nerve fibers were observed in the deeper regions
      of the dermis. Neuropeptide Y-, nitric oxide-, and vasoactive intestinal
      polypeptide-immunoreactive fibers were completely absent. Their observations
      support the hypothesis that the sensory and autonomic defects reported in
      hereditary sensory and autonomic neuropathy are based on profound developmental
      alterations of the peripheral nervous system.

PMID- 10891922
TI  - Reorganization of the motor cortex in a patient with congenital hemiparesis and
      mirror movements.
AB  - Abnormal branching of corticospinal fibers from the unaffected motor cortex is
      responsible for mirror movements in patients with congenital hemiparesis, but it
      is unknown which mechanisms enable these patients to lateralize motor activity.
      Using multiunit electromyographic analysis and transcranial magnetic stimulation,
      the authors provide evidence for nonbranched crossed and uncrossed corticospinal
      projections and intracortical inhibition of the mirror hand. They propose that
      this remarkable reorganization of the unaffected motor cortex helps these
      patients to reduce mirror movements.

PMID- 10891923
TI  - Activated microglia in dementia with Lewy bodies.
AB  - To investigate the role of cerebral inflammation in dementia with Lewy bodies
      (DLB), activated microglial cells were quantified in postmortem brain tissue.
      Patients with pure DLB (LB but no AD pathology) had significantly greater numbers
      of cells than nondemented control subjects, but fewer than patients with either
      pure AD or DLB combined with AD. There was a positive correlation between the
      numbers of activated microglia and LB in different brain regions. This study
      demonstrates the presence of significant inflammation in DLB, even in the absence
      of AD pathology.

PMID- 10891924
TI  - Longitudinal change in hippocampal volume as a function of apolipoprotein E
      genotype.
AB  - The epsilon4 allele of the apolipoprotein E (APOE) gene confers an increased risk
      for the development of AD. The authors compared longitudinal rates of change in
      hippocampal volume as a function of APOE genotype in nondemented elderly
      individuals. Rate of volumetric loss was significantly greater among epsilon4+
      compared with epsilon4- individuals. These results indicate that individuals
      positive for the APOE epsilon4 allele may show a greater rate of hippocampal
      atrophy than their epsilon4- counterparts, even in the absence of a diagnosis of
      AD.

PMID- 10891925
TI  - The serotonergic agent m-chlorophenylpiperazine induces migraine attacks: A
      controlled study.
AB  - In a double-blind study versus placebo, the serotonergic agent m
      chlorophenylpiperazine (mCPP) was administered to 20 healthy control subjects and
      19 migraineurs to investigate the ability of mCPP (0.5 mg/kg) to induce typical
      migraine attacks. In the following 24 hours there were more migraines after mCPP
      than after placebo in both groups. These findings are consistent with involvement
      of 5HT2B,2C,1A receptor subtypes in the pathophysiology of migraine.

PMID- 10891926
TI  - Aura in some patients with familial hemiplegic migraine can be stopped by
      intranasal ketamine.
AB  - Migraine aura is probably caused by cortical-spreading depression. No treatment
      for acute and severe migraine aura has been described previously. The effect of
      ketamine (25 mg intranasally) was studied in 11 patients with severe, disabling
      auras resulting from familial hemiplegic migraine. In five patients ketamine
      reproducibly reduced the severity and duration of the neurologic deficits,
      whereas in the remaining six patients no beneficial effect was seen. Ketamine
      offers, for the first time, a possible treatment option for severe and prolonged
      aura.

PMID- 10891927
TI  - Survey of migraineurs referred to headache specialists: care, satisfaction, and
      outcomes.
AB  - The authors report a survey of 281 migraineurs recently referred to headache
      specialists by primary care physicians. Compared with care before referral,
      specialists spent substantially more time with patients and were more likely to
      ask patients to take a prophylactic drug and to keep a headache diary, to discuss
      migraine triggers, and to prescribe 5-hydroxytryptamine1B/1D agonists (triptans).
      After referral, patients reported improved satisfaction with care and significant
      decreases in frequency, duration, and severity of attacks.

PMID- 10891928
TI  - Guillain-Barre syndrome: An unusual presentation of West Nile virus infection.
AB  - West Nile fever is a mosquito-borne febrile illness seen in Africa, Asia, and
      Europe, but reported in North America only once. The recent outbreak in New York
      City represents the first time this virus has been detected in North America.
      West Nile virus usually causes mild symptoms, though rarely it can cause
      neurologic diseases, with a fatal outcome or permanent neurologic sequelae. We
      describe an elderly patient with West Nile virus infection who presented with
      Guillain-Barre syndrome.

PMID- 10891929
TI  - Embolic strokes in an 8-year-old girl.

PMID- 10891930
TI  - FLAIR MRI in sporadic Creutzfeldt-Jakob disease.

PMID- 10891931
TI  - Migraine with ectopic hyperprolactinemia from uterine fibroids.

PMID- 10891932
TI  - Benign cough headache is responsive to acetazolamide.

PMID- 10891933
TI  - Hypothermia and thermoregulatory derangements induced by valproic acid.

PMID- 10891934
TI  - Reversed clock phenomenon: A right-hemisphere syndrome.

PMID- 10891935
TI  - Rhombencephalitis caused by West Nile fever virus.

PMID- 10891936
TI  - Evaluation of surgery for Parkinson's disease: report of the Therapeutics and
      Technology Assessment Subcommittee of the American Academy of Neurology.

PMID- 10891937
TI  - Carbamazepine in comparative trials: pharmacokinetic characteristics too often
      forgotten.

PMID- 10891938
TI  - Use of Bacille Calmette-Guerin (BCG) in multiple sclerosis.

PMID- 10891939
TI  - A case-controlled MRI/MRA study of neurovascular contact in hemifacial spasm.

PMID- 10891941
TI  - JAMA 100 years ago: A SYSTEM OF PERSONAL BIOLOGIC EXAMINATIONS-THE CONDITION OF
      ADEQUATE MEDICAL AND SCIENTIFIC CONDUCT OF LIFE

PMID- 10891940
TI  - Immediate-release and controlled-release carbidopa/levodopa in PD: A 5-year
      randomized multicenter study.

PMID- 10891942
TI  - Psychiatric help may shrink some waistlines.

PMID- 10891943
TI  - Researchers describe findings for targeted cancer therapies.

PMID- 10891946
TI  - Health agencies update: islamic medieval medicine

PMID- 10891945
TI  - Health agencies update: "Book of Life" rough draft

PMID- 10891947
TI  - Health agencies update: treating mild asthma

PMID- 10891948
TI  - Health agencies update: toxic chemicals and defects

PMID- 10891949
TI  - Assessing prevention interventions by "number needed to treat".

PMID- 10891950
TI  - Assessing prevention interventions by "number needed to treat".

PMID- 10891951
TI  - Assessing prevention interventions by "number needed to treat".

PMID- 10891952
TI  - Assessing prevention interventions by "Number needed to treat"

PMID- 10891953
TI  - Molecular epidemiology and tuberculosis control.

PMID- 10891954
TI  - Molecular epidemiology and tuberculosis control.

PMID- 10891955
TI  - Molecular epidemiology and tuberculosis control

PMID- 10891956
TI  - Estrogen as a treatment for Alzheimer disease.

PMID- 10891957
TI  - Estrogen as a treatment for Alzheimer disease.

PMID- 10891958
TI  - Estrogen as a treatment for alzheimer disease

PMID- 10891959
TI  - Prognostic value of cortisol response in septic shock.

PMID- 10891960
TI  - Prognostic value of cortisol response in septic shock.

PMID- 10891961
TI  - Prognostic value of cortisol response in septic shock

PMID- 10891962
TI  - Relationship of baseline serum cholesterol levels in 3 large cohorts of younger
      men to long-term coronary, cardiovascular, and all-cause mortality and to
      longevity.
AB  - CONTEXT: Based on observational and interventional data for middle-aged cohorts
      (aged 40-64 years), serum cholesterol level is known to be an established major
      risk factor for coronary heart disease (CHD). However, findings for younger
      people are limited, and the value of detecting and treating hypercholesterolemia
      in younger adults is debated. OBJECTIVE: To evaluate the long-term impact of
      unfavorable serum cholesterol levels on risk of death from CHD, cardiovascular
      disease (CVD), and all causes. DESIGN, SETTING, AND PARTICIPANTS: Three
      prospective studies, from which were selected 3 cohorts of younger men with
      baseline serum cholesterol level measurements and no history of diabetes mellitus
      or myocardial infarction. A total of 11,017 men aged 18 through 39 years screened
      in 1967-1973 for the Chicago Heart Association Detection Project in Industry
      (CHA); 1266 men aged 25 through 39 years examined in 1959-1963 in the Peoples Gas
      Company Study (PG); and 69,205 men aged 35 through 39 years screened in 1973-1975
      for the Multiple Risk Factor Intervention Trial (MRFIT). MAIN OUTCOME MEASURES:
      Cause-specific mortality during 25 (CHA), 34 (PG), and 16 (MRFIT) years of follow
      up; mortality risks; and estimated life expectancy in relation to baseline serum
      cholesterol levels. RESULTS: Death due to CHD accounted for 26%, 34%, and 28% of
      all deaths in the CHA, PG, and MRFIT cohorts, respectively; and CVD death for
      34%, 42%, and 39% of deaths in the same cohorts, respectively. Men in all 3
      cohorts with unfavorable serum cholesterol levels (200-239 mg/dL [5.17-6.18
      mmol/L] and >/=240 mg/dL [>/=6.21 mmol/L]) had strong gradients of relative
      mortality risk. For men with serum cholesterol levels of 240 mg/dL or greater
      (>/=6.21 mmol/L) vs favorable levels (<200 mg/dL [<5.17 mmol/L]), CHD mortality
      risk was 2.15 to 3.63 times greater; CVD disease mortality risk was 2.10 to 2.87
      times greater; and all-cause mortality was 1.31 to 1.49 times greater.
      Hypercholesterolemic men had age-adjusted absolute risk of CHD death of 59 per
      1000 men in 25 years (CHA cohort), 90 per 1000 men in 34 years (PG cohort), and
      15 per 1000 men in 16 years (MRFIT cohort). Absolute excess risk was 43.6 per
      1000 men (CHA), 81.4 per 1000 men (PG), and 12.1 per 1000 men (MRFIT). Men with
      favorable baseline serum cholesterol levels had an estimated greater life
      expectancy of 3.8 to 8.7 years. CONCLUSIONS: These results demonstrate a
      continuous, graded relationship of serum cholesterol level to long-term risk of
      CHD, CVD, and all-cause mortality, substantial absolute risk and absolute excess
      risk of CHD and CVD death for younger men with elevated serum cholesterol levels,
      and longer estimated life expectancy for younger men with favorable serum
      cholesterol levels. JAMA. 2000;284:311-318

PMID- 10891963
TI  - Long-term satisfaction and psychological and social function following bilateral
      prophylactic mastectomy.
AB  - CONTEXT: Prophylactic mastectomy is a preventive option for women who wish to
      reduce their risk of breast cancer. There has been concern about possible
      negative psychological sequelae following this procedure. However, few data are
      available regarding long-term satisfaction and psychological and social function
      following this procedure. OBJECTIVE: To evaluate patients' long-term satisfaction
      and psychological and social function following prophylactic mastectomy. DESIGN,
      SETTING, AND PARTICIPANTS: Descriptive study of all women known to be alive (n =
      609) who had a family history of breast cancer and elected to undergo bilateral
      prophylactic mastectomy at a large, tertiary US health care clinic between 1960
      and 1993, 94% (n = 572) of whom completed a study questionnaire. MAIN OUTCOME
      MEASURES: Satisfaction with procedure and effects on psychological and social
      function, based on responses to the study-specific questionnaire. RESULTS: Mean
      time from prophylactic mastectomy to last follow-up was 14.5 years. Most women
      (70%) were satisfied with the procedure; 11% were neutral; and 19% were
      dissatisfied. Among the psychological and social variables, the most striking
      finding was that 74% reported a diminished level of emotional concern about
      developing breast cancer. The majority of women reported no change/favorable
      effects in levels of emotional stability (68%/23%), level of stress (58%/28%),
      self-esteem (69%/13%), sexual relationships (73%/4%), and feelings of femininity
      (67%/8%). Forty-eight percent reported no change in their level of satisfaction
      with body appearance; 16% reported favorable effects. However, 9%, 14%, 18%, 23%,
      25%, and 36% reported negative effects in these 6 variables, respectively.
      CONCLUSIONS: This study suggests that positive outcomes following prophylactic
      mastectomy include decreased emotional concern about developing breast cancer and
      generally favorable psychological and social outcomes. These must be weighed
      against the irreversibility of the decision, potential problems with implants and
      reconstructive surgery, and occurrence of adverse psychological and social
      outcomes in some women. JAMA. 2000;284:319-324

PMID- 10891964
TI  - Mapping of a gene for severe pediatric gastroesophageal reflux to chromosome
      13q14.
AB  - CONTEXT: Gastroesophageal reflux (GER) has not previously been widely regarded as
      a hereditary disease. A few reports have suggested, however, that a genetic
      component may contribute to the incidence of GER, especially in its severe or
      chronic forms. OBJECTIVE: To identify a genetic locus that cosegregates with a
      severe pediatric GER phenotype in families with multiple affected members.
      DESIGN: A genome-wide scan of families affected by severe pediatric GER using
      polymorphic microsatellite markers spaced at an average of 8 centimorgans (cM),
      followed by haplotyping and by pairwise and multipoint linkage analyses. SETTING:
      General US community, with research performed in a university tertiary care
      hospital. SUBJECTS: Affected and unaffected family members from 5 families having
      multiple individuals affected by severe pediatric GER, identified through a
      patient support group. MAIN OUTCOME MEASURES: Determination of inheritance
      patterns and linkage of a genetic locus with the severe pediatric GER phenotype
      by logarithm-of-odds (lod) score analysis, considering a lod score of 3 or
      greater as evidence of linkage. RESULTS: In these families, severe pediatric GER
      followed an autosomal dominant hereditary pattern with high penetrance. A gene
      for severe pediatric GER was mapped to a 13-cM region on chromosome 13q between
      microsatellite markers D13S171 and D13S263. A maximum multifamily 2-point lod
      score of 5.58 and a maximum multifamily multipoint lod score of 7.15 were
      obtained for marker D13S1253 at map position 35 cM when presumptively affected
      persons were modeled as unknown (a maximum multipoint score of 4.88 was obtained
      when presumptively affected persons were modeled as unaffected). CONCLUSION:
      These data suggest that a gene for severe pediatric GER maps to chromosome 13q14.
      JAMA. 2000;284:325-334

PMID- 10891965
TI  - Trends in twin birth outcomes and prenatal care utilization in the United States,
      1981-1997.
AB  - CONTEXT: Multiple births account for an increasing percentage of all low-birth
      weight infants, preterm births, and infant mortality in the United States. Since
      1981, the percentage of women with multiple births who received intensive
      prenatal care (defined as a high number of visits, exceeding the recommendation
      of the American College of Obstetricians and Gynecologists by approximately 1 SD
      beyond the mean number of visits for women initiating care within each trimester)
      has increased significantly. OBJECTIVES: To explore the hypothesis that more
      aggressive management of twin-birth pregnancies may be associated with changes in
      birth outcomes in this population. DESIGN, SETTING, AND SUBJECTS: Cross-sectional
      and trend analysis of data from the National Center for Health Statistics' birth
      and infant death records for all twin births occurring in the United States
      between 1981 and 1997, excluding those with missing or inconsistent data. MAIN
      OUTCOME MEASURES: Trends in preterm birth, low birth weight, preterm and term
      small-for-gestational-age (SGA) births, and infant mortality, by level of
      prenatal care utilization. RESULTS: The preterm birth rate for twins increased
      from 40.9% in 1981 to 55.0% in 1997. The percentage of low-birth-weight infants
      increased from 51.0% to 54.0%. The preterm SGA rate also increased from 11.9% to
      14.1%, while the term SGA rate decreased from 30.7% to 20.5%. For women with
      intensive prenatal care utilization, the preterm birth rate increased from 35.1%
      to 55.8%, compared with an increase from 50.6% to 59.2% among women with only
      adequate use. Twin preterm deliveries involving either induction or first
      cesarean delivery also increased from 21.9% to 27.3% between 1989-1991 and 1995
      1997. The twin infant mortality rate for women with intensive prenatal care use
      declined between 1983 and 1996 and remained lower than the overall twin infant
      mortality rate. CONCLUSIONS: An apparent increase in medical interventions in the
      management of twins may result in the seeming incongruity of more prenatal care
      and more preterm births; however, these data suggest that women with intensive
      prenatal care utilization also have a lower infant mortality rate. JAMA.
      2000;283:335-341

PMID- 10891966
TI  - Role of exercise stress testing and safety monitoring for older persons starting
      an exercise program.
AB  - While the benefits of physical activity and exercise among older persons are
      becoming increasingly clear, the role of exercise stress testing and safety
      monitoring for older persons who want to start an exercise program is unclear.
      Current guidelines regarding exercise stress testing likely are not applicable to
      the majority of persons aged 75 years or older who are interested in restoring or
      enhancing their physical function through a program of physical activity and
      exercise. In addition to being expensive and of unproven benefit, the current
      policy of routine exercise stress testing potentially could deter many older
      persons from participating in an exercise program. Research is needed to
      investigate current physician practices, evaluate the risk of adverse cardiac
      events, determine the role of pharmacological stress testing, and measure and
      compare absolute and relative exercise intensities. To assist clinicians, we
      offer a set of recommendations regarding precautions that can be taken to
      minimize the risk of adverse cardiac events among previously sedentary older
      persons who do not have symptomatic cardiovascular disease and are interested in
      starting an exercise program. JAMA. 2000;284:342-349

PMID- 10891967
TI  - Pemphigoid: clinical, histologic, immunopathologic, and therapeutic
      considerations.
AB  - Autoimmune blistering diseases are generally distinct entities characterized by
      relatively consistent clinical, histologic, and immunopathologic findings. These
      disorders may cause impaired adhesion of epidermis to epidermal basement membrane
      (eg, the pemphigoid group of disorders [bullous, gestational, and mucous
      membrane]) or impaired adhesion of epidermal cells to each other (eg, the
      pemphigus group of disorders). Recent studies have shown that these disorders are
      characterized by autoantibodies that often display pathogenic (ie, blister
      forming) activity in passive transfer models. Interestingly, the autoantigens
      targeted by these patients' autoantibodies represent important structural
      proteins that promote cell matrix (eg, pemphigoid) or cell-to-cell (eg,
      pemphigus) adhesion in skin. Autoimmune blistering diseases are characterized by
      substantial morbidity (pruritus, pain, disfigurement), and in some instances,
      mortality (secondary to loss of epidermal barrier function). Treatment with
      systemic immunosuppressives has reduced morbidity and mortality in patients with
      these diseases. JAMA. 2000;284:350-356

PMID- 10891968
TI  - Users' guides to the medical literature: XXIII. Qualitative research in health
      care A. Are the results of the study valid? Evidence-Based Medicine Working
      Group.
AB  - Quantitative research is designed to test well-specified hypotheses, determine
      whether an intervention did more harm than good, and find out how much a risk
      factor predisposes persons to disease. Equally important, qualitative research
      offers insight into emotional and experiential phenomena in health care to
      determine what, how, and why. There are 4 essential aspects of qualitative
      analysis. First, the participant selection must be well reasoned and their
      inclusion must be relevant to the research question. Second, the data collection
      methods must be appropriate for the research objectives and setting. Third, the
      data collection process, which includes field observation, interviews, and
      document analysis, must be comprehensive enough to support rich and robust
      descriptions of the observed events. Fourth, the data must be appropriately
      analyzed and the findings adequately corroborated by using multiple sources of
      information, more than 1 investigator to collect and analyze the raw data, member
      checking to establish whether the participants' viewpoints were adequately
      interpreted, or by comparison with existing social science theories. Qualitative
      studies offer an alternative when insight into the research is not well
      established or when conventional theories seem inadequate. JAMA. 2000;284:357-362

PMID- 10891969
TI  - Promoting early diagnosis and treatment of type 2 diabetes: the National Diabetes
      Education Program.

PMID- 10891970
TI  - Early detection of high cholesterol levels in young adults.

PMID- 10891971
TI  - Treatment of McArdle disease.

PMID- 10891972
TI  - Leukoaraiosis: reifying rarefaction.

PMID- 10891973
TI  - To treat, or not to treat: the therapeutic dilemma of idiopathic monosymptomatic
      demyelinating syndromes.

PMID- 10891974
TI  - beta-peptide immunization: a possible new treatment for Alzheimer disease.

PMID- 10891975
TI  - Current treatment of neuromuscular diseases.

PMID- 10891976
TI  - Immunological assays for understanding neuroimmune interactions.

PMID- 10891977
TI  - Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo
      controlled crossover trial.
AB  - OBJECTIVE: To determine whether treatment with creatine can improve exercise
      intolerance in myophosphorylase deficiency (McArdle disease). DESIGN: Double
      blind, placebo-controlled crossover study with oral creatine monohydrate
      supplementation. PATIENTS: Nine patients with biochemically and genetically
      proven McArdle disease were treated. INTERVENTION: Five days of daily high-dose
      creatine intake (150 mg/kg body weight) were followed by daily low-dose creatine
      intake (60 mg/kg). Each treatment phase with creatine or placebo lasted 5 weeks.
      MAIN OUTCOME MEASURES: The effect of treatment was estimated at the end of each
      treatment phase by recording clinical scores, ergometer exercise test results,
      phosphorus 31 nuclear magnetic resonance spectroscopy, and surface
      electromyography. RESULTS: Of 9 patients, 5 reported improvement of muscle
      complaints with creatine. Force-time integrals (P =.03) and depletion of
      phosphocreatine (P =.04) increased significantly during ischemic exercise with
      creatine. Phosphocreatine depletion also increased significantly during aerobic
      exercise (P =.006). The decrease of median frequency in surface electromyograms
      during contraction was significantly larger (P =.03) with creatine. CONCLUSION:
      This is the first controlled study indicating that creatine supplementation
      improves skeletal muscle function in McArdle disease.

PMID- 10891978
TI  - What is the significance of leukoaraiosis in patients with acute ischemic stroke?
AB  - BACKGROUND: Leukoaraiosis (LA) may have specific clinical correlates in patients
      with stroke, but this is not well investigated, so that the significance of LA in
      patients with stroke remains unclear. METHODS: In a study of 2289 patients with a
      first-ever acute ischemic stroke, LA was noted in 149 by the use of baseline
      computed tomography of the brain. These patients were compared with the non-LA
      group. Statistical tests, including Fisher exact test or a chi(2) test, were used
      to compare variables, and a multivariate approach using stepwise logistic
      regression was performed. RESULTS: Patients with LA were significantly older
      (73.7 vs 62.7 years; P<. 001), and had a higher incidence of hypertension (72.5%
      vs 47.1%; P<. 001) and subcortical or lacunar infarction (40.3% vs 25.4% and
      21.5% vs 8.0%, respectively; P<.001) on neuroimaging studies, compared with the
      non-LA group. The most common cause of stroke in the LA group was presumed to be
      small-artery disease associated with hypertension (46% vs 13.5% in the non-LA
      group). Age and hypertension were very strongly associated with LA (respective
      odds ratios [95% confidence intervals], 1.06 [1.04-1.08] and 2.33 [1.60-3. 39]).
      In addition to these risk factors, a close relationship was found between LA and
      nonsevere stenosis (<50%) of the internal carotid artery (odds ratio, 2.23 [95%
      confidence interval, 1.32-3. 76]), although the significance of this association
      remains speculative. The outcome at 1 month after stroke was similar in both
      groups. CONCLUSION: Our results provide further evidence that LA is related
      primarily to small-vessel disease.

PMID- 10891979
TI  - Multiple sclerosis-from probable to definite diagnosis: a 7-year prospective
      study.
AB  - OBJECTIVES: To investigate the rate of progression from probable to clinically
      definite multiple sclerosis (MS) and to define patients who had rapidly (within 1
      year) progressed to a definite diagnosis. DESIGN: A 7-year prospective study.
      PATIENTS: A group of 163 patients experiencing their first episode of neurologic
      symptoms suggestive of MS. All patients had brain magnetic resonance imaging that
      demonstrated at least 3 demyelinating lesions at onset. RESULTS: Within the
      follow-up period (mean, 42 months; range, 13-84 months), 136 patients (83.4%) had
      an additional relapse and were thus defined as having clinically definite MS,
      whereas 27 patients (16.6%) were defined as having clinically probable MS. Most
      of the 136 patients with clinically definite MS (57.6%, 94 patients) experienced
      the additional relapse within 1 year. Demographic and clinical parameters at
      presentation were analyzed to identify variables predictive of rapid progression
      (within 1 year) to clinical definite MS. Motor involvement at onset was the only
      clinical parameter associated with rapid progression to a definite diagnosis.
      Survival curves demonstrated that polysymptomatic involvement and higher Extended
      Disability Status Scale score at presentation correlated with rapid progression
      to definite diagnosis. CONCLUSION: Most patients with a diagnosis of probable MS
      and positive brain magnetic resonance imaging will progress rapidly to clinically
      definite MS.

PMID- 10891980
TI  - Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced
      Parkinson disease.
AB  - CONTEXT: Subthalamic nucleus (STN) stimulation may be effective in ameliorating
      parkinsonian symptoms even to the extent to permit levodopa withdrawal.
      OBJECTIVES: To analyze the efficacy of STN stimulation in patients with Parkinson
      disease (PD) and to determine if levodopa may be withdrawn after surgery. DESIGN:
      Before-after trial. SETTING: Referral center, hospitalized care. PATIENTS:
      Fifteen patients with advanced PD. INTERVENTIONS: Microelectrode-guided bilateral
      STN high-frequency stimulation. OUTCOME MEASURES: Before surgery patients were
      evaluated in off-medication and on-medication conditions. Dopaminergic drug
      dosages were reduced after surgery, aiming for complete withdrawal. Six months
      after surgery, patients were reeavaluated in off- and on-medication conditions,
      with the stimulation turned on and off. RESULTS: Total Unified Parkinson's
      Disease Rating Scale (UPDRS) motor score in the off-medication condition improved
      by 65.9%; and axial symptoms, bradykinesia, rigidity, and tremor improved by
      65.8%, 60.4%, 66.1%, and 81.1%, respectively. UPDRS part II scores were reduced
      by 71.8% and Schwab and England scores improved by 45.3%. Levodopa was withdrawn
      in 8 patients and the overall levodopa dose was reduced 80.4%. "Off" time was
      reduced 89.7% and the severity of dyskinesias decreased 80.6% after surgery. All
      results reached significance (P<.001). Stimulation of the STN achieved
      antiparkinsonian effect similar to that of treatment with levodopa. No life
      threatening adverse effects occurred. CONCLUSIONS: Bilateral STN stimulation
      safely improves all parkinsonian symptoms, decreases or eliminates the need for
      levodopa, and ameliorates motor fluctuations and dyskinesias. Complete withdrawal
      of levodopa is feasible with this technique and the overall motor effect of STN
      stimulation is quantitatively comparable to that obtained with levodopa.

PMID- 10891981
TI  - Triphasic perfusion computed tomography in acute middle cerebral artery stroke: a
      correlation with angiographic findings.
AB  - OBJECTIVE: To evaluate the usefulness of triphasic perfusion computed tomography
      (TPCT) in diagnosing middle cerebral artery (MCA) occlusion and in assessing the
      perfusion deficit and collateral circulation in patients with acute ischemic
      stroke. BACKGROUND: Conventional angiography is the criterion standard for the
      diagnosis of MCA occlusion and for the assessment of perfusion deficit and
      collateral blood supply. The risk of hemorrhagic transformation after
      recanalization of occluded arteries by thrombolytic therapy is considered high
      when pretherapeutic residual flow is markedly reduced. PATIENTS AND METHODS: In 8
      patients within 3 hours of onset of acute MCA stroke, precontrast computed
      tomographic scans were taken, and then TPCT was performed after power-injector
      controlled intravenous administration of contrast media. Sequential images of
      early, middle, and late phases were obtained. The whole procedure took 5 minutes.
      Perfusion deficit on TPCT was graded as "severe" or "moderate," depending on the
      state of collateral flow. Digital subtraction angiography (DSA) was performed in
      all patients within 6 hours of acute stroke. Direct intra-arterial urokinase
      infusion was begun immediately after the angiographic superselection of the MCA
      occlusion site in 6 of the 8 patients within 7 hours of onset (range, 4.3-6.2
      hours). RESULTS: The DSA findings showed occlusion of the MCA stem (n = 1) and at
      the bifurcation (n = 4). The sites of proximal MCA occlusion could be identified
      on the early and middle images of TPCT in all 5 patients. On DSA findings, all 8
      patients had a zone of perfusion deficit with markedly slow leptomeningeal
      collaterals and a zone of perfusion deficit with no collaterals. The zone of
      severe perfusion deficit on TPCT corresponded to the zone of perfusion deficit
      with no or few collaterals on angiography, and the zone of moderate perfusion
      deficit on TPCT corresponded to that of perfusion deficit with markedly slow
      leptomeningeal collaterals. Early parenchymal hypoattenuation on precontrast
      computed tomography was confined to the zone of severe perfusion deficit on TPCT.
      The initial National Institutes of Health Stroke Scale score correlated better
      with the total extent of severe perfusion deficit and moderate perfusion deficit
      on TPCT than that of severe perfusion deficit alone. After direct intra-arterial
      thrombolysis within 7 hours of onset, symptomatic hemorrhagic transformation did
      not develop in 4 patients with small severe perfusion deficit (33% or less of the
      presumed MCA territory). However, the remaining 2 patients with large severe
      perfusion deficit (more than 50% of the presumed MCA territory) deteriorated to
      death with hemorrhagic transformation. CONCLUSIONS: Triphasic perfusion computed
      tomography is useful for diagnosing proximal MCA occlusion and assessing
      perfusion deficit and collateral circulation as reliably as DSA. The zone of
      severe perfusion deficit on TPCT may be presumed to be the ischemic core, and
      that of moderate perfusion deficit, the penumbra zone. Triphasic perfusion
      computed tomography may be used as a rapid and noninvasive tool to make
      thrombolysis safer.

PMID- 10891982
TI  - Usefulness of triphasic perfusion computed tomography for intravenous
      thrombolysis with tissue-type plasminogen activator in acute ischemic stroke.
AB  - BACKGROUND: Intravenous thrombolysis for acute ischemic stroke has been
      investigated in several clinical trials without enough information on collateral
      blood flow and perfusion deficit in the ischemic areas. The therapeutic time
      window varies from patient to patient depending on these factors. Triphasic
      perfusion computed tomography (TPCT) can provide this information as reliably as
      conventional angiography. OBJECTIVE: To assess the safety and efficacy of
      thrombolysis within 3 or 7 hours of stroke onset according to the extent of
      perfusion deficit on TPCT. METHODS: In 46 patients with acute middle cerebral
      artery (MCA) territory stroke, TPCT was performed with power injector-controlled,
      intravenous administration of contrast media after taking precontrast CT scans.
      Sequential scans of early, middle, and late phases were performed. The entire
      procedure took 5 minutes. Depending on collateral blood flow, the perfusion
      deficit on TPCT was graded as "severe perfusion deficit" or "moderate perfusion
      deficit." Twenty-nine patients were excluded based on clinical, laboratory, and
      TPCT findings. Seventeen patients were treated with an intravenous recombinant
      tissue-type plasminogen activator, 0.9 mg/kg. The 17 treated patients were
      divided into 2 groups: group 1 with small severe perfusion deficit (</=33% of the
      presumed MCA territory) and group 2 with medium-sized severe perfusion deficit
      (>33% but </=50% of the presumed MCA territory). The 13 patients in group 1 were
      treated within 7 hours of onset and the 4 patients in group 2 were treated within
      3 hours. RESULTS: Initial mean National Institutes of Health Stroke Scale score
      was 12.1 (range, 6.0-20.0) in group 1 and 19.0 (range, 18.0-21. 0) in group 2.
      The initial score correlated better with the total extent of moderate perfusion
      deficit and severe perfusion deficit than that of severe perfusion deficit alone.
      Mean time lapse to thrombolysis was 4.2 hours (range, 1.5-7.0 hours) in group 1
      and 2.2 hours (range, 1.9-2.5 hours) in group 2. Eight patients (47%), 7 from
      group 1 and 1 from group 2, improved by 4 points or more from baseline Stroke
      Scale score within 24 hours of thrombolysis. Patients with moderate perfusion
      deficit of 50% or more of MCA territory (n = 4) had a better chance of early
      improvement than did those (n = 13) with moderate perfusion deficit of less than
      50% (4 of 4 vs 4 of 13). No fatal hemorrhage occurred. Only 1 patient (6%) had
      symptomatic small basal ganglia hemorrhage after thrombolysis. CONCLUSIONS:
      Thrombolysis can be safely performed within 3 or 7 hours of stroke onset
      according to the extent of severe perfusion deficit on TPCT. A larger extent of
      moderate perfusion deficit on TPCT may predict early improvement after
      thrombolysis.

PMID- 10891983
TI  - Diffusion-weighted magnetic resonance imaging identifies the "clinically
      relevant" small-penetrator infarcts.
AB  - BACKGROUND: Most patients initially seen with a clinical syndrome consistent with
      a small-penetrator infarct (SPI) also harbor multiple, chronic, hyperintense,
      white matter lesions on conventional magentic resonance imaging (ie, T2-weighted
      image [T2WI] and fluid-attenuation inversion recovery [FLAIR] imaging). Diffusion
      weighted imaging (DWI) can identify the clinically relevant "index infarction" in
      such circumstances, since it differentiates between acute and chronic lesions.
      OBJECTIVE: To determine the clinical and radiological predictors associated with
      misidentification of an SPI as acute using T2WI and FLAIR images in patients with
      an acute SPI seen on DWI. PATIENTS: Sixty-seven consecutive patients who had an
      SPI. METHODS: Two independent examiners, provided with brief clinical
      information, but blinded to DWI findings, sought a clinically appropriate lesion
      on T2WI and FLAIR imaging in 67 consecutive patients found to have an SPI seen on
      DWI. RESULTS: The index infarction based on evaluation of T2WI or FLAIR images
      was in a different location than the acute lesion as identified by DWI in 9 (13%)
      and 11 (16%) of 67 patients, respectively. Both T2WI and FLAIR imaging were rated
      normal in another 9% of the patients. Multivariate analysis showed that small
      lesion size (<10 mm) was the only predictor of misidentifying the clinically
      appropriate lesion on conventional magnetic resonance imaging (P<.01).
      CONCLUSIONS: T2-weighted imaging and FLAIR imaging fail to identify the
      clinically relevant SPI in almost one quarter of the patients found to have a
      lesion on DWI. The characteristics of DWI make it well suited for the detection
      of acute small infarcts. Diffusion-weighted imaging is necessary to consistently
      define the clinical-anatomical relations in patients initially seen with SPIs.

PMID- 10891984
TI  - A quantitative study of water diffusion in multiple sclerosis lesions and normal
      appearing white matter using echo-planar imaging.
AB  - OBJECTIVES: We used an optimized echo-planar pulse sequence for isotropically
      weighted diffusion imaging (1) to measure mean diffusivity (D) in lesions and
      normal-appearing white matter (NAWM) in the entire brain from patients with
      mildly disabling relapsing-remitting multiple sclerosis (MS), (2) to compare the
      D of NAWM from patients with that of white matter from normal controls, (3) to
      evaluate whether lesions classified on the basis of their appearance on enhanced
      T1-weighted scans have different D, and (4) to investigate the relationship
      between diffusion changes in lesions and NAWM. METHODS: Dual-echo and diffusion
      weighted scans were obtained from 35 patients with relapsing-remitting MS and 24
      sex- and age-matched normal controls. Postcontrast T1-weighted images were also
      obtained from the patients. After creating D maps and image coregistration, D
      values were measured for MS lesions larger than 5 mm and for 22 NAWM areas from
      each subject. RESULTS: All NAWM areas studied had significantly higher D in
      patients than in controls. A total of 173 lesions were identified on the dual
      echo scans from patients. The average D for these lesions was significantly
      higher than that of NAWM. Twenty-two lesions were enhancing and 60 were
      classified as T1-hypointense. No significant difference in D values was found
      between enhancing and nonenhancing lesions, while the average D of T1-hypointense
      lesions was significantly higher than the average D of T1-isointense lesions.
      There was no significant correlation between the average D in lesions and NAWM.
      CONCLUSIONS: This study shows that diffusion-weighted imaging is able to identify
      MS lesions with severe tissue disruption. It also shows that widespread increased
      diffusion can be measured in the NAWM from patients with MS, and suggests that
      such changes are, at least partially, independent of larger abnormalities.

PMID- 10891985
TI  - Autonomic performance and dehydroepiandrosterone sulfate levels in HIV-1-infected
      individuals: relationship to TH1 and TH2 cytokine profile.
AB  - BACKGROUND: Products of immune activation, including cytokines and lipid membrane
      derivatives, have been implicated in the pathogenesis of the neurologic sequelae,
      including autonomic dysfunction, associated with human immunodeficiency virus 1
      (HIV-1) infection. In animal models, autonomic and endocrine dysfunction are
      associated with an altered cytokine profile. OBJECTIVES: To investigate the
      relationship between markers of immune activation (beta(2)-microglobulin), HIV-1
      disease progression (CD4(+) cell count and viral load), and autonomic nervous
      system performance and to assess the relationship between autonomic performance,
      plasma levels of dehydroepiandrosterone sulfate (DHEAS), and T(H)1 and T(H)2
      cytokine profile. METHODS: Thirty-one HIV-1-infected individuals and 22 HIV-1
      negative controls were evaluated with a comprehensive neurologic,
      neuropsychological, and autonomic examination. Interleukin 4 and interferon gamma
      were measured by enzyme-linked immunosorbent assay in the supernatant of
      stimulated peripheral blood mononuclear cells. RESULTS: A composite measure of
      autonomic performance (AZ score) was significantly lower (worse autonomic
      function) in patients compared with controls (P=.04). A lower AZ score was
      associated with higher beta(2)-microglobulin serum levels and a lower CD4(+) cell
      count. Interleukin 4 levels were significantly inversely associated with AZ score
      (P=.01), whereas interferon gamma levels were significantly positively associated
      with DHEAS levels (P=.04). CONCLUSIONS: Our data show significant associations
      between markers of immune activation and disease progression and a composite
      measure of autonomic function in HIV-1-infected individuals. In addition, they
      suggest that poor autonomic function and low DHEAS plasma levels tend to be
      associated with an unbalanced cytokine profile.

PMID- 10891986
TI  - Human immunodeficiency virus-associated pure motor lumbosacral polyradiculopathy.
AB  - BACKGROUND: Neuromuscular disease is a common manifestation of human
      immunodeficiency virus infection and acquired immunodeficiency syndrome, but
      isolated and severe pathology confined to the motor roots or anterior horn cells
      are not a recognized clinical entity. OBJECTIVE: To describe the novel clinical
      presentation of human immunodeficiency virus-related polyradiculopathy
      manifesting as isolated severe motor symptoms confined to the legs. DESIGN: A
      case series comprising 4 patients identified prospectively during a 6-month
      period. SETTING: Patients were seen in the Department of Neurology, Groote Schuur
      Hospital, Cape Town, South Africa. This is an 800-bed teaching hospital, with
      approximately 5000 patients seen annually in the Department of Neurology.
      PATIENTS: Patients were identified by their unique presentation with a severe
      isolated motor neuropathy in the lower limbs. All were Xhosa-speaking African
      women. RESULT: Early human immunodeficiency virus infection may be associated
      with pure motor lumbosacral polyradiculopathy. CONCLUSION: It remains unclear
      whether this clinical syndrome should be regarded as a variant of the Guillain
      Barre syndrome or whether it represents a unique disorder associated with early
      human immunodeficiency virus infection.

PMID- 10891987
TI  - Confirmation of subtle motor changes among presymptomatic carriers of the
      Huntington disease gene.
AB  - OBJECTIVE: To confirm that subtle changes in motor function and reaction time are
      present in presymptomatic individuals carrying the expanded Huntington disease
      (HD) allele. DESIGN: A case-control, double-blind study comparing presymptomatic
      HD gene carriers (PSGCs) and nongene carriers (NGCs) at risk for HD. SETTING: The
      Department of Medical and Molecular Genetics at a general clinical research
      center in a midwestern city. PARTICIPANTS: Two hundred sixteen individuals at
      risk for HD who were asymptomatic by self-report and who did not have manifest HD
      on results of clinical examination, including PSGCs (n = 61) and NGCs (n = 155).
      MEASURES: Molecular testing was used to determine the number of CAG repeats in
      the HD gene. A quantified neurologic examination and a battery of physiological
      measures of central nervous system function measuring speed of movement and
      reaction time were administered. RESULTS: On neurologic examination, the PSGCs
      exhibited significantly more definite or possible abnormalities than NGCs for
      overall oculomotor function, saccade velocity, optokinetic nystagmus, chorea of
      the extremities, and dystonia of the extremities (P<.05). The PSGCs also had
      significantly slower performance for auditory reaction time, visual reaction
      time, visual reaction time with decision, movement time, movement time with
      decision, and button-tapping time, compared with the NGCs (P<.05). CONCLUSIONS:
      Subtle changes in motor function, speed of movement, and reaction time are
      present in HD gene carriers who do not exhibit definite choreiform movements and
      who do not have sufficient signs to make a clinical diagnosis of HD. In addition,
      a trend toward slower speed of movement and reaction time was observed among this
      population as their neurologic abnormalities increased.

PMID- 10891988
TI  - Familial progressive vestibulocochlear dysfunction caused by a COCH mutation
      (DFNA9).
AB  - OBJECTIVE: To describe the decline of vestibulocochlear function in a man with
      vestibulocochlear dysfunction caused by a Pro51Ser mutation within the COCH gene
      on chromosome 14q12-13 (DFNA9). METHODS: A follow-up of more than 15 years was
      performed in a single case. Clinical investigations were supplemented by
      oculomotor, vestibular, and auditory tests. RESULTS: A 50-year-old man had had
      progressive sensorineural hearing loss and dysequilibrium for 15 years; he had
      been asymptomatic at the age of 35 years. He suffered from instability in the
      dark, head movement-dependent oscillopsia, paroxysmal positional vertigo, and
      vertigo with and without nausea. Hearing impairment started unilaterally,
      predominantly in the high frequencies. He also reported tinnitus. Disease
      progressed to severe bilateral high-frequency hearing impairment and vestibular
      areflexia. Fluctuation of vestibulocochlear function was documented and mentioned
      by the patient. CONCLUSIONS: Our patient proved to suffer from an autosomal
      dominant vestibulocochlear disorder caused by a COCH gene mutation. The
      remarkable medical history has some features in common with Meniere disease;
      however, there are also different clinical and neurophysiological features. In
      the family, phenotypic variability is present.

PMID- 10891989
TI  - Gait disturbances in patients with pontine medial tegmental lesions: clinical
      characteristics and gait analysis.
AB  - OBJECTIVE: To determine the clinical characteristics of gait disorders in
      patients with pontine medial tegmental lesions. DESIGN: We compared features of
      gait disorders between patients with infarcts in the medial tegmentum and those
      with stroke in other areas of the pons (pathological control subjects) by
      measuring electromyographic results of lower limb muscles and several
      biomechanical parameters. PATIENTS: Two patients with infarcts in the rostral
      medial tegmentum and 4 control subjects. Two of the control patients had lesions
      in the pontine base, while the lesions in the other 2 were in the pontine
      tegmentum and base (combined lesions). RESULTS: Patients with rostral medial
      tegmental lesions and controls with pontine base lesions showed unstable walking
      characterized by irregular angular displacements and foot pressures. However,
      they differed by the following 3 features. (1) Rostral medial tegmental lesions
      elicited truncal ataxia without limb ataxia. In comparison, pontine base lesions
      elicited limb ataxia without truncal ataxia and caused hemiparesis. (2)
      Instability was more severe and persistent in patients with the former lesions
      than in those with the latter lesions. Slowness of walking speed and prolongation
      of the double-support period were clearly observed in the former group. (3)
      Electromyographic changes characteristic of cerebellar ataxia were clearly
      evident in patients with rostral medial tegmental lesions. The electromyographic
      amplitudes of the gastrocnemius and tibialis anterior muscles were almost
      constant throughout the gait cycle, resulting in the disappearance of the
      inherent periodic pattern of each muscle. CONCLUSION: Medial tegmental lesions in
      the rostral pons cause prolonged and severe unstable walking that resembles
      spinocerebellar ataxic pattern, and impairment of the spinocerebellar loop might
      be the pathomechanism underlying such a gait disturbance.

PMID- 10891990
TI  - Novel prion protein gene mutation in an octogenarian with Creutzfeldt-Jakob
      disease.
AB  - BACKGROUND: The transmissible spongiform encephalopathies constitute a
      fascinating and biologically unique group of invariably fatal neurodegenerative
      disorders that affect both animals and humans. Creutzfeldt-Jakob disease (CJD),
      Gerstmann-Straussler-Scheinker syndrome, and fatal familial insomnia represent
      the more common human phenotypes. Excluding the small number of iatrogenically
      transmitted cases, approximately 85% to 90% of patients develop CJD without
      identifiable explanation, with an increasing number of different mutations in the
      prion protein gene (PRNP) recognized as probably causative in the remainder.
      OBJECTIVE: To report on an 82-year-old woman with pathologically confirmed CJD
      found unexpectedly to harbor a novel mutation in PRNP. METHODS: Routine clinical
      investigations were undertaken to elucidate the cause of the rapidly progressive
      dementia and neurological decline manifested by the patient, including magnetic
      resonance imaging of the brain, electroencephalography, and cerebrospinal fluid
      analysis for the 14-3-3 beta protein. Standard postmortem neuropathological
      examination of the brain was performed, including immunocytochemistry of
      representative sections to detect the prion protein. Posthumous genetic analysis
      of the open reading frame of PRNP was performed on frozen brain tissue using
      polymerase chain reaction and direct sequencing. RESULTS: Concomitant with the
      exclusion of alternative diagnoses, the presence of characteristic periodic sharp
      wave complexes on the electroencephalogram in combination with a positive result
      for 14-3-3 beta protein in the cerebrospinal fluid led to a confident clinical
      diagnosis of CJD, confirmed at autopsy. There was no family history of dementia
      or similar neurological illness, but patrilineal medical information was
      incomplete. Unexpectedly, full sequencing of the PRNP open reading frame revealed
      a single novel mutation consisting of an adenine-to-guanine substitution at
      nucleotide 611, causing alanine to replace threonine at codon 188. CONCLUSIONS:
      In addition to expanding the range of PRNP mutations associated with human prion
      diseases, we believe this case is important for the following reasons. First,
      from an epidemiological perspective, the avoidance of occasional incorrect
      classification of patients manifesting neurodegenerative disorders that may have
      a genetic basis requires systematic genotyping, particularly when there are
      uncertainties regarding the family history. Second, the incidence of spongiform
      encephalopathy in elderly patients beyond the typical age range may be
      underestimated and does not preclude a genetic basis. Finally, as a corollary,
      this case highlights problematic issues in human transmissible spongiform
      encephalopathies, as illustrated by disease penetrance and age of onset in
      genotype-phenotype correlations.

PMID- 10891991
TI  - Valproate, hyperandrogenism, and polycystic ovaries: a report of 3 cases.
AB  - BACKGROUND: Reproductive endocrine disorders characterized by menstrual
      disorders, polycystic ovaries, and hyperandrogenism seem to be common among women
      treated with sodium valproate for epilepsy. OBJECTIVE: To describe the
      development of valproate-related reproductive endocrine disorders in women with
      epilepsy. DESIGN: Case report. PATIENTS: Three patients developed a reproductive
      endocrine disorder during treatment with valproate. It was characterized by
      hyperandrogenism and polycystic ovaries in all cases, and it was associated with
      weight gain and menstrual disorders in 2 of the 3 women. RESULTS: Replacing
      valproate with lamotrigine resulted in a decrease in serum testosterone
      concentrations in all 3 women. The polycystic changes disappeared from the
      ovaries in 2 of the women after valproate therapy was discontinued, and the 2
      women who had gained weight and developed amenorrhea while being treated with
      valproate lost weight and resumed menstruating after the change in medication.
      CONCLUSIONS: The 3 cases presented here illustrate the development of
      reproductive endocrine disorders after the initiation of valproate therapy in
      women with epilepsy. The disorders were characterized by hyperandrogenism and
      polycystic ovaries in all cases, and were associated with weight gain and
      menstrual disorders in 2 of the 3 women. An evaluation of ovarian structure and
      function should be considered in women of reproductive age being treated with
      valproate for epilepsy, especially if they develop menstrual cycle disturbances
      during treatment.

PMID- 10891992
TI  - Tick paralysis in the United States: a photographic review.

PMID- 10891993
TI  - Souvenir from war.

PMID- 10891994
TI  - Trauma to the central nervous system may result in formation or enlargement of
      multiple sclerosis plaques.

PMID- 10891995
TI  - Trauma does not precipitate multiple sclerosis.

PMID- 10891996
TI  - Trauma and Multiple Sclerosis.

PMID- 10891997
TI  - Neurology was there: 1945.

PMID- 10891999
TI  - Hyperammonia Possibly due to Corticosteroids.

PMID- 10891998
TI  - Hyperammonia possibly due to corticosteroids.

PMID- 10892000
TI  - Dipyridamole plus aspirin in cerebrovascular disease.

PMID- 10892001
TI  - Dipyridamole Plus Aspirin in Cerebrovascular Disease.

PMID- 10892002
TI  - The Kettil Bruun Society: an international forum for social and epidemiological
      research on alcohol.

PMID- 10892003
TI  - Conversation with Martha Sanchez-Craig.

PMID- 10892004
TI  - Using cue reactivity to evaluate medications for treatment of cocaine dependence:
      a critical review.
AB  - AIMS: The aim of this article is to examine the validity of a cue-reactivity
      paradigm for evaluating medications to treat cocaine dependence and to critically
      review cocaine pharmacotherapy studies that use this method. METHODS: A Medline
      computerized search was performed to identify randomized, controlled medication
      studies for cocaine dependence that employed a cue-reactivity paradigm. Relevant
      bibliographies of these articles were also reviewed. Eleven placebo-controlled
      studies were identified in the English language literature. Four of these studies
      used agents that block dopaminergic neurotransmission, two studies used agents
      that modify the serotonergic system, and two studies used nicotinergic agents.
      The other three studies employed a mood stabilizer, an opioid antagonist or a
      psychostimulant. RESULTS: There has been little research examining the
      theoretical basis of the cue-reactivity model, as applied to the screening of
      medications to treat cocaine dependence. From a methodological viewpoint, most
      studies have shown that exposure to cocaine-related stimuli increases subjective
      and physiological reactivity in cocaine-dependent patients, but methods used to
      present the cues and to measure cue reactivity have not been consistent across
      studies. Similarly, the observed increase in subjective and physiological
      reactivity to cocaine cues has varied within and across studies. CONCLUSIONS: If
      a cocaine cue-reactivity paradigm is to be used to evaluate medications for
      treatment of cocaine dependence, the validity of the model must first be
      demonstrated and a consistent methodology for cue presentation and measurement of
      responses must be developed.

PMID- 10892005
TI  - Estimating the prevalence of problem drug use in inner London: a discussion of
      three capture-recapture studies.
AB  - AIMS: To provide an evidence base of estimates of the prevalence of problem drug
      use in inner London. DESIGN: Re-analysis of three capture-recapture studies using
      subjects aged 15-49 years, that aim to estimate the hidden population from
      analysing the overlaps between three data sources. SETTING: Newham (1995) Camden
      and Islington (C&I) (1993/4) and Lambeth, Southwark and Lewisham (LSL) (1992).
      PARTICIPANTS: Each study collected data from three sources of problem drug users
      including: the Regional Drug Misuse Database, specialist drug agencies, HIV
      tests, social services, police arrests and court records. In LSL opiate users
      were analysed separately. The studies identified 1832 individuals in LSL, 543 in
      Newham, and 1321 in C&I. MEASUREMENTS: Poisson models were fitted to the data
      testing different interactions between the data sources representing potential
      dependencies. The simplest model was selected on the basis of its AIC score and
      log-likelihood ratio tests. FINDINGS: The number of hidden problem drug users
      were estimated to be 12,500 (95% CI 9600-16,100) in LSL with 4400 (3200-6100)
      opiate users; 7000 (5000-10,000) in C&I and 3800 (2000-7200) in Newham. The
      prevalence of problem drug use in those aged 15-49 was estimated to be 3.1% (2.5
      3.9%) in LSL with 1.3% (1.0-1.6%) opiate users; and 3.6% (2.7-4.9%) and 3.3% (1.9
      5.7%) in C&I and Newham, respectively. CONCLUSIONS: Despite the inherent problems
      with capture-recapture methods, our three studies establish an evidence base for
      estimates of problem drug use in London. It is important that a larger study is
      carried out in London.

PMID- 10892006
TI  - Patterns of cannabis use, abuse and dependence over time: incidence, progression
      and stability in a sample of 1228 adolescents.
AB  - AIMS: To present data on the incidence of cannabis use at follow-up, and its
      progression, stability, abuse and dependence in a representative sample of
      adolescents (N = 1228), aged 14-17 years at "baseline"--the outset of the study-
      in Munich, Germany. DESIGN: The study employed a prospective longitudinal design
      using a representative population sample. The mean follow-up time was 19.7
      months. The Composite International Diagnostic Interview (M-CIDI) was used to
      assess patterns of use, abuse and dependence according to DSM-IV criteria.
      FINDINGS: (1) In our sample, 34.8% of males and 30.2% of females had tried
      cannabinoids at least once. (2) Of those who used cannabis repeatedly (two or
      four times) at baseline, 26.1% stopped using by follow-up; the majority went on
      to regular use in the follow-up period. Similarly, only 17.7% of the regular
      users at the outset stopped using cannabis completely; 74.2% continued their
      pattern of regular use. Thus, the higher the baseline use pattern, the higher was
      the probability of continued or heavier use during follow-up. (3) Although the
      cumulative life-time incidence for DSM-IV cannabis abuse (3.5%) in this age group
      was low, it is noteworthy that complete diagnostic remissions were relatively
      rare (31.7% for dependence, 41.1% for abuse). (4) There was considerable
      concurrent use of other drugs. CONCLUSIONS: Cannabis use was almost as widespread
      in this sample of adolescents in Germany as in similar age groups in metropolitan
      areas of North America. There was a relatively low spontaneous remission rate
      among regular and repeated users. Cannabis use in adolescence appears to be less
      transient than many people would believe.

PMID- 10892007
TI  - Covariates of cannabis use progression in a representative population sample of
      adolescents: a prospective examination of vulnerability and risk factors.
AB  - AIMS/DESIGN: This study reports findings concerning risk factors for first,
      "repeated" and "regular" use of cannabis in respondents (N = 1228) who were aged
      14-17 years at the outset (i.e. at "baseline") as part of a longitudinal
      prospective community study (EDSP). Risk factors were assessed at baseline or by
      separate interviews with the respondents' parents. Cumulative life-time cannabis
      use was the main outcome measure in this study--assessed by information from both
      the baseline and the follow-up investigation at an average of 19.7 months later.
      A cumulative logistic regression model was used to estimate associations.
      FINDINGS: Using seven of a total of 25 variables examined, the final model
      classified 72.1% of respondents correctly. Family history of substance use
      disorders, self-esteem and competence, unconditional commitment to not using
      drugs, immediate availability of drugs, peer group drug use and previous history
      of nicotine dependence and alcohol use disorders all contributed significantly to
      the final model, predicting the progression to cannabis use from "no use", to
      "one time only", "repeated use", and "regular use". CONCLUSION: In addition to
      well-documented risk factors such as peer group pressure, availability, low self
      esteem and competence, findings suggest that family history and prior experiences
      with legal drugs play a significant role in the early development of cannabis
      consumption in teenagers.

PMID- 10892008
TI  - Ecstasy and new patterns of drug use: a normal population study.
AB  - AIMS: (i) To describe illegal drug use patterns in an adolescent normal
      population sample with special emphasis on MDMA, ecstasy; (ii) to investigate
      where ecstasy is introduced in a hypothesized drug use sequence, and (iii) to
      contrast the predictors of ecstasy use with those of other illegal substances.
      Special attention was given to the relationship to subcultural music preferences
      and house-party-going. DESIGN: A school-based survey of the total cohort of
      adolescents enrolled in the school system in a city. PARTICIPANTS: 10,812
      adolescents, age 14-17 years, response rate 94.3%. SETTING: Oslo, the capital and
      only metropolitan town in Norway. MEASUREMENTS: Social class was measured by the
      occupation standard ISCO 88, questions were posed as regards frequency of alcohol
      use and alcohol intoxication, cigarette smoking and use of cannabis,
      amphetamines, ecstasy and heroin. Alcohol problems were measured by a shortened
      version of Rutgers Alcohol Problem Index (RAPI), conduct problems were measured
      according to the four categories of acts forming the basis of the diagnosis
      conduct disorder in DSM-IV, internalizing mental health problems were measured
      using items from Hopkins Symptoms Checklist (HCL). A number of questions were
      asked as regards subcultural music preferences and house-party-going. STATISTICAL
      MODELS: A hypothesized cumulative sequence in drug use was investigated by means
      of latent class analysis, and the predictors of the various patterns of drug use
      were estimated and compared by means of multinominal logistic regression
      analysis. FINDINGS: The use of ecstasy was often intermingled with the use of
      cannabis, amphetamines and heroin, in a pattern of polydrug use. The latent class
      analysis revealed the following drug use sequence: (1) alcohol, (2) cigarettes,
      (3) cannabis, (4) amphetamines, (5) ecstasy and (6) heroin. There was no
      significant association between ecstasy use and parental social class or
      residential area of the town. All patterns of illegal drug use were highly
      associated with cigarette smoking, alcohol use, alcohol problems and conduct
      problems, whereas the associations with internalizing mental health problems were
      of less magnitude. Multinominal logistic regression analysis revealed that the
      use of ecstasy (E) was significantly more weakly associated with cigarette
      smoking than were the use of cannabis only (C), amphetamines (A) and the
      combination of ecstasy and amphetamines (A + E). The association between E and
      conduct problems (CP) was weaker than the association between CP and A and A + E.
      Finally, there were associations between E and A + E and House/Techno preferences
      and house-party-going, which were not found for C and A. CONCLUSIONS: Ecstasy is
      used by adolescents who use other legal and illegal substances in a polydrug-use
      pattern. The substance is introduced late in a hypothesized drug use sequence.
      Even so, ecstasy use seems to differ from the use of, e.g. amphetamines, in that
      the association with smoking and conduct problems is weaker and that the
      associations with subcultural music preferences and house-party-going are much
      stronger.

PMID- 10892009
TI  - Contrasting levels of adolescent drug use between adjacent urban and rural
      communities in Scotland.
AB  - AIMS: To compare life-time prevalence of illicit drug use between adolescents
      resident in adjacent urban and rural localities. DESIGN: Samples of
      schoolchildren attending urban and rural comprehensive schools (n = 2558) were
      obtained using an identical questionnaire survey method. SETTING: Respondents
      were recruited from 10 schools in two contrasting adjacent local authorities.
      Five representative schools in each locality were chosen. PARTICIPANTS: All
      children present in each school, in the two final compulsory school years, were
      eligible for this study. MEASUREMENTS: Respondents were asked to provide detailed
      information about their place of residence and use of illegal drugs. The data
      obtained in schools were compared with local geographical statistics, such as
      levels of deprivation. FINDINGS: As expected from the demographics of their
      respective localities, the urban schools displayed higher levels of deprived
      children and lower levels of school achievement. These socio-economic differences
      were not reflected in reported levels of life-time drug use. This was true both
      between and within the urban and rural samples. CONCLUSION: These findings
      suggest that adolescent drug use in Scotland is not particularly concentrated in
      areas of urban deprivation.

PMID- 10892010
TI  - The relationship between alcohol consumption patterns and injury.
AB  - AIMS AND DESIGN: A case-control design was employed to quantify the risk of
      injury after the recent consumption of alcohol. PARTICIPANTS AND SETTING: A total
      of 797 cases and 797 controls were interviewed throughout 1997. A response rate
      of 82% was calculated for eligible cases who were approached by an interviewer.
      The rate for interviews conducted of all people presenting with an injury during
      the study period was 67%. Cases were injured patients from a hospital emergency
      unit. Controls were matched on suburb and were interviewed at home regarding
      activities leading up to the time of their matched case's injury. MEASUREMENTS:
      Cases and controls were questioned about the injury event and alcohol and other
      drug use consumed in the 6 hours prior to the injury. They were also breath
      tested and medical records were checked for validation purposes. FINDINGS:
      Logistic regression analysis produced an odds ratio of 3.4 (95% CI: 1.8-6.4) for
      the risk of sustaining an injury after consuming more than 60 g of alcohol in a 6
      hour period, after controlling for demographic variables. The risk of injury at
      different levels of alcohol use was substantially higher for females with a
      significant odds ration of 9.6 at greater than 60 g of alcohol compared to 2.1
      for men. CONCLUSIONS: These results need to be interpreted cautiously, but
      provide additional support that the risk of injury increases with the quantity of
      alcohol consumed and that the risk of injury is significantly higher for women.

PMID- 10892011
TI  - Alcoholic beverage choice, risk perception and self-reported drunk driving:
      effects of measurement on risk analysis.
AB  - AIMS: The present study examined effects of measurement on risk curve analysis in
      an application involving prediction of frequency and indicator measures of drunk
      driving with beverage-specific alcohol consumption and risk perception measures.
      DESIGN AND PARTICIPANTS: From a 1995 in-person survey of the US adult household
      population (response rate = 77%) the responses of 1260 adult drivers who reported
      any drinking in the prior year were selected for analysis. Regression and
      graphical techniques were used to investigate relationships between drinking
      pattern, beverage choice, perception of risks of drinking before driving, and
      frequency of drunk driving. MEASUREMENTS: Self-reported drunk driving
      (occurrence) was measured by a question assessing driving after drinking enough
      to be in trouble if stopped by the police within the prior 12 months; those
      affirming this (n = 191) were asked how many times they did so (frequency).
      Alcohol consumption was assessed by beverage and in combination. Risk perception
      was assessed as a factor score from three correlated measures. Demographic
      variables included age, ethnicity, education and income. FINDINGS: Controlling
      for demographics, heavy beer consumption (p < 0.01) more than heavy wine (NS) or
      liquor/spirits (p < 0.05) intake was strongly predictive of risk perception. A
      regression analysis showed a significant interaction between heavy beer
      consumption and perceived risk (p < 0.001) in predicting reported frequency of
      drunk driving, after controlling for heavy beer consumption (p < 0.05), total
      alcohol consumption and risk perception (both ps < 0.001). No interactions were
      important in equivalent models predicting dichotomous occurrence. Graphic
      analysis showed the shape of the risk curve is altered when frequency of drunk
      driving is taken into account rather than simple occurrence. CONCLUSIONS:
      Individuals' underestimation of beer's intoxicating effects, compared to other
      alcoholic beverage types, helps explain beer's over-representation in drinking
      driving violation reports. There is a need for creative public health campaigns
      designed to inform young men of beer's alcohol content and associated risks.

PMID- 10892012
TI  - Opioid overdose: an international perspective.

PMID- 10892013
TI  - Identification of major histocompatibility complex class II-associated peptides
      derived from freshly prepared rat Langerhans cells using MALDI-PSD and Edman
      degradation.
AB  - The isolation and identification is described of MHC class II-bound peptides
      derived from Langerhans cells. A combination of preparative micro-HPLC, MALDI-MS,
      Edman degradation was used for determining the amino acid sequence of MHC
      associated peptides. Sample handling was crucial because fractions containing
      trace amounts of material require immediate storage at -80 degrees C to prevent
      peptide losses.

PMID- 10892014
TI  - A comparative study on methods of optimal sample preparation for the analysis of
      oligonucleotides by matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - Metal adducts (e.g., Na+ and K+) significantly hinder the analysis of
      oligonucleotides by matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry (MALDI-TOF-MS). Although a number of sample purification
      methods exist, to date no comparative study exists to determine the most
      efficient method for purifying oligonucleotides. The objective of this work was
      to perform such a study. Several different oligonucleotide samples were
      synthesized. Aliquots of these samples were then purposely contaminated with
      sodium acetate to generate representative contaminated (salted) oligonucleotide
      samples. A number of popular oligonucleotide purification techniques were then
      tested as to their effectiveness at removing Na+ from the salted samples. The
      effectiveness of Na+ removal was qualitatively assessed by comparing the MALDI
      mass spectra of the original sample, the salted sample, and the salted sample
      after purification. Micropipet tips packed with C18 reversed-phase packing
      material (e.g., Zip Tips) appear to be the most effective means of purifying the
      oligonucleotides investigated. Minidialysis was found to be an effective
      alternative for purifying higher molecular weight oligonucleotides (> 10,000 u).

PMID- 10892015
TI  - Characterization of ginseng saponins using electrospray mass spectrometry and
      collision-induced dissociation experiments of metal-attachment ions.
AB  - Electrospray mass spectrometry (ESMS) and collision-induced dissociation (CID)
      methodologies have been developed for the structural characterization of ginseng
      saponins (ginsenosides). Ginsenosides are terpene glycosides containing a
      triterpene core to which one to four sugars may be attached. They are neutral
      molecules which readily form molecular metal-attachment ions in positive ion ESMS
      experiments. In the presence of ammonium hydroxide intense deprotonated ions are
      generated. Both positive and negative ion ESMS experiments were found to be
      useful for molecular mass and structure determination of ten ginsenoside
      standards. Negative ion experiments made possible the determination of the
      molecular mass of each ginsenoside standard, the mass of the triterpene core and
      the masses and sequences of the sugar residues. Positive ion ESMS experiments
      with the alkali metal cations Li+ or Na+ and the transition metal cations Co2+,
      Ni2+ and Zn2+ were also useful in determining molecular masses. These alkali and
      transition metal cations form strongly bonded attachment ions with the
      ginsenosides. As a result, the CID mass spectra of the metal attachment ions show
      a variety of (structure characteristic) fragmentations. These experiments can be
      used to determine the identity of the triterpene core, the types and attachment
      points of sugars to the core and the nature of the O-glycosidic linkages in the
      appended disaccharides. Combining the results from the negative and positive ion
      experiments provides a promising approach to the structure analysis of this class
      of natural products.

PMID- 10892016
TI  - Nano-electrospray and microbore liquid chromatography-ion trap mass spectrometry
      studies of copper complexation with MHC restricted peptides.
AB  - The formation of copper/peptide complex ions by nano-electrospray and microbore
      HPLC-electrospray mass spectrometry has been investigated for major
      histocompatibility complex (MHC) class I and class II restricted peptides. Post
      column addition of copper(II) acetate following microbore HPLC-MS separation was
      carried out using a mixing T-piece or via the sheath flow inlet of the
      electrospray source. Optimal analytical conditions for copper complex ion
      formation were determined by variation of copper concentration, pH, nebulization
      gas supply and spray voltage. Tandem mass spectrometry of copper/peptide complex
      ions provides peptide sequence information and insight into the peptide chelation
      sites. Copper associated y fragment ions dominate the product ion spectrum for
      non-histidine containing peptides, but both b and y copper complex ions were
      observed for the histidine containing MHC class I associated peptide gp70.

PMID- 10892017
TI  - HPLC-electrospray mass spectrometry for the analysis of temoporfin-poly(ethylene
      glycol) conjugates.
AB  - The photodynamic therapeutic agent temoporfin, 5,10,15,20-tetra(m
      hydroxyphenyl)chlorin (m-THPC) conjugated with poly(ethylene glycol) 2000 (PEG),
      has been analysed by high performance liquid chromatography (HPLC), linked to
      electrospray ionisation mass spectrometry (ESI-MS). Sufficient separation of m
      THPC-PEG 2000 oligomers was achieved, enabling determination of molecular mass.
      The use of ESI-MS alone could not achieve this, because of too great a complexity
      in the mass spectrum, resulting from the presence of four PEG 2000 side chains
      with a wide molecular mass distribution. The technique is applicable to similar
      PEG conjugated compounds.

PMID- 10892018
TI  - Preparation of single-stranded PCR products for electrospray ionization mass
      spectrometry using the DNA repair enzyme lambda exonuclease.
AB  - Electrospray ionization mass spectrometry (ESI-MS) has been utilized to obtain
      accurate mass measurements of intact PCR products; however, single-stranded PCR
      products are necessary to detect sequence modifications such as base
      substitutions, additions or deletions. The locations of these modifications can
      subsequently be determined using additional stages of mass spectrometry. The
      recombinant enzyme lambda exonuclease selectively digests one strand of a DNA
      duplex from a 5' phosphorylated end leaving the complementary strand intact.
      Using this rapid enzymatic step, we were able to produce single-stranded PCR
      products by digestion of an intact PCR product derived from the Human Tyrosine
      Hydroxylase (HUMTHO1) gene, which contains a tetrameric repeating motif. The non
      template directed 3' adenylation common when using Taq polymerase resulted in
      three distinct species (blunt-ended, mono-adenylated and di-adenylated), which
      added complexity to the spectrum of the double-stranded product. The data from
      the single-stranded products shows that one strand is preferentially adenylated
      over the other, which cannot be determined from the mass spectrum of the double
      stranded PCR product alone. The ESI-FTICR (Fourier transform ion cyclotron
      resonance) mass spectra of the lambda exonuclease treated PCR products exhibited
      less than expected signal-to-noise (S/N) ratios. This is attributed to inaccurate
      concentration calculations due to remaining double-stranded PCR product amplified
      with unphosphorylated primers, and to matrix effects contributed by the lambda
      exonuclease reaction buffer. To further test this hypothesis, we investigated and
      determined the limit of detection to be 0.27 microM using standard curve
      statistics for single acquisitions of a synthetic 75-mer. The concentrations of
      the noncoding and coding strands produced by lambda exonuclease digestion were
      calculated to be 0.29 and 0.37 microM, respectively, taking into account the
      presence of double-stranded product. The products were electrosprayed from
      concentrations at the limit of detection requiring the averaging of 5-10
      acquisitions to produce a sufficient S/N ratio, indicating that product
      concentration, base composition and matrix effects play a combined, significant
      role in detection of lambda exonuclease treated PCR products. Although additional
      work will be required to further exploit this strategy, lambda exonuclease
      clearly provides mass spectrometrists with a method to generate single-stranded
      PCR products.

PMID- 10892019
TI  - Structural analysis of drug-DNA adducts by tandem mass spectrometry.
AB  - The utility of electrospray ionisation (ESI) tandem mass spectrometry (MS/MS) for
      the characterisation of ligand-oligonucleotide adducts is demonstrated with
      adducts formed between the oligonucleotide 5'-CACGTG-3' and both a platinating
      agent, cis-diamminedichloroplatinum(II) (cisplatin), and an alkylating ligand, n
      bromohexylphenanthridinium bromide (phenC6Br). We have demonstrated previously
      that negative ion MS/MS spectra of alkylated oligonucleotides show a highly
      specific fragmentation pathway that enables the site of binding of the ligand to
      be readily identified. In comparison, the positive ion ESI-MS/MS spectra reported
      here also show a single major fragmentation pathway, but the dominant ion is the
      protonated ligand-base adduct. MS/MS of this ion confirms the site on binding of
      the ligand to the guanine base. MS/MS spectra of cisplatin adducts show much less
      specific fragmentation than alkylated adducts, particularly in the negative ion
      mode. This suggests that the ESI-MS/MS spectra of ligand-DNA adducts are strongly
      influenced by the extent to which the ligand weakens the glycosidic bond in the
      residue to which it is bound. For platinating agents, which do not labilise the
      glycosidic bond, additional experiments involving MS/MS of source-generated
      product ions were required to enable isomeric adducts to be distinguished.

PMID- 10892020
TI  - C-terminal peptide sequencing using acetylated peptides with MSn in a quadrupole
      ion trap.
AB  - MS/MS has been used to sequence peptides and small proteins for a number of
      years. This method allows one to isolate the peptide of interest, which makes it
      possible to analyze impure samples and unseparated mixtures, such as protein
      digests. Collision-induced dissociation (CID) of the selected peptide ion
      generates the product ions that provide sequence information. However, often the
      MS/MS spectrum does not provide adequate information for complete sequence
      determination. The quadrupole ion trap has the capability to do multiple stages
      of mass spectrometry, MSn, which can increase the information available to
      determine the peptide sequence. A regular and predictable dissociation pattern
      for peptides further simplifies this analysis. By forming predominantly one type
      of ion, ambiguity is removed as to whether the ion is N- or C-terminal. This
      pattern can also be advantageous in that ion intensity remains concentrated for
      the next stage of MS/MS. In this work, a method to take advantage of the MSn
      capabilities of the quadrupole ion trap by controlling the dissociation pathways
      is explored. Dissociation is altered by acetylating the N-terminus of the
      peptide. MSn of a variety of acetylated peptides is used to determine the effects
      of the identity of the C-terminal residue and the length of the peptide on the
      dissociation pathways observed.

PMID- 10892021
TI  - Rapid isolation method for lipopolysaccharide and lipid A from gram-negative
      bacteria.
AB  - A fast, convenient extraction method for lipopolysaccharide (LPS), using a
      commercial RNA isolating reagent, allows the isolation of LPS or lipid A from low
      milligram (dry weight) quantities of bacterial cells. The method avoids the use
      of specialized equipment and has been used for processing relatively large
      numbers of samples. The major components of the commercial RNA isolating reagent,
      Tri-Reagent, are phenol and guanidinium thiocyanate in aqueous solution. The
      bacterial cell membranes are disrupted with guanidinium thiocyanate, which
      eliminates the need for mechanical cell disruption (e.g. French press) or
      heating. LPS and its degradation products, with particular attention paid to its
      bioactive lipid A portion, were measured and compared with those from the most
      common conventional extraction method, hot phenol-water. Negative ion quadrupole
      ion trap and matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) mass spectrometry, fatty acid composition analysis by capillary gas
      chromatography, total and free phosphate by UV spectrophotometry and sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that LPS and
      lipid A isolated using the Tri-Reagent approach were cleaner and suffered less
      degradation through loss of phosphate and (or) fatty acyl side chains from lipid
      A. The Tri-Reagent extraction method generated low free phosphate contamination,
      11% of the total phosphate concentration, whereas the hot phenol-water extraction
      method gave approximately 58% as free, inorganic phosphate. Similar results were
      observed for the degradation of fatty acyl side chains. The time required by the
      new method is considerably shorter (two or three days) than that required by
      conventional hot phenol-water extraction (about two weeks).

PMID- 10892022
TI  - Use of capillary electrophoresis and indirect detection to quantitate in
      capillary enzyme-catalyzed microreactions.
AB  - The use of capillary electrophoresis and indirect detection to quantify reaction
      products of in-capillary enzyme-catalyzed microreactions is described. Migrating
      in a capillary under conditions of electrophoresis, plugs of enzyme and substrate
      are injected and allowed to react. Capillary electrophoresis is subsequently used
      to measure the extent of reaction. This technique is demonstrated using two model
      systems: the conversion of fructose-1,6-bisphosphate to dihydroxyacetone
      phosphate and glyceraldehyde-3-phosphate by fructose-biphosphate aldolase (ALD,
      EC 4.1.2.13), and the conversion of fructose-1,6-bisphosphate to fructose-6
      phosphate by fructose-1,6-bisphospatase (FBPase, EC 3.1.3.11). These procedures
      expand the use of the capillary as a microreactor and offer a new approach to
      analyzing enzyme-mediated reactions.

PMID- 10892023
TI  - Direct determination of t,t-muconic acid in human urine by two-dimensional liquid
      chromatography.
AB  - The accurate determination of E,E-2,4-hexadiendioic acid (t,t-muconic acid), an
      important urinary biomarker of benzene exposure, is directly performed in human
      urine by a new two-dimensional liquid chromatographic method. After a first
      partial separation of urine components by a reversed-phase mechanism and the
      focalisation of the anionic analytes on a small anion-chromatographic column, a
      conventional ion-chromatographic analysis with UV detection is carried out. The
      analytical procedure is fully controlled by the HPLC instrumentation software
      using an eight-port switch valve. If compared with conventional one-dimensional
      procedures, the new method produces chromatograms containing a limited number of
      well resolved peaks and consequently allows better analytical performances: no
      interfering peaks, absence of bias, repeatability better than 5% in the
      concentration range 0.09-5 mg dm-3 and a detection limit of 4.0 micrograms dm-3
      (alpha = beta = 0.05) for the analysis of real samples.

PMID- 10892024
TI  - Determination of estrone and 17 beta-estradiol in human hair by gas
      chromatography-mass spectrometry.
AB  - An efficient procedure is described for the determination of estrone and 17 beta
      estradiol in hair by gas chromatography-mass spectrometry (GC-MS). The method
      involves alkyloxycarbonylation with isobutyl chloroformate (isoBCF) of phenolic
      hydroxy groups after alkaline digestion of hair samples. The resulting
      isobutyloxycarbonyl derivatives of estrone and 17 beta-estradiol are extracted
      with hexane and subjected to chlorodifluoroacetyl derivatization in order to
      protect the remaining alcoholic hydroxy groups. When GC-MS with selected ion
      monitoring (SIM) was used, the quantitative ions were at m/z 270 and 384 in the
      electron ionization mass spectra for estrone and 17 beta-estradiol, respectively.
      The detection limits for SIM of the steroids were 1 and 2 pg, respectively, and
      the SIM responses were linear with correlation coefficients varying from 0.991 to
      0.994 in the concentration range 0.2-4.0 ng g-1 for the estrogens studied. The
      detection of estrone and 17 beta-estradiol in hair samples was possible in the
      concentration range of 0.24-1.30 ng g-1. The concentrations of the two estrogens
      detected were different in male and female hair samples.

PMID- 10892025
TI  - Determination of mercapturic acids in urine by solid-phase extraction followed by
      liquid chromatography-electrospray ionization mass spectrometry.
AB  - A novel method for the determination of five kinds of mercapturic acids, found in
      urine as metabolites of alkylbenzenes, based on liquid chromatography
      electrospray ionization mass spectrometry is described. A solid-phase extraction
      procedure was used for the extraction of the mercapturic acids from urine and the
      separation was performed on a reversed-phase C30 column. The detection limits
      were in the range 2.4-3.2 ng ml-1.

PMID- 10892026
TI  - Guidelines on good publication practice. Committee on Publications Ethics (COPE).

PMID- 10892027
TI  - Binding of some Diocleinae lectins to the mucosal surfaces of the eye and mouth.
AB  - Controlled delivery of diagnostic or therapeutically active agents to the eye and
      oral cavity is limited by the efficient removal mechanisms that exist in these
      areas. In this work, recently isolated, purified and characterised Brazilian bean
      lectins were examined for their ability to bind to the buccal and sublingual
      mucosa, cornea and conjunctiva of rat, with regard to their potential therapeutic
      use. These lectins were labelled using biotin (long arm) N-hydroxysuccinimide
      ester and a technique developed at the University of Portsmouth. Evaluation of
      binding after 15 min contact with intact (unfixed) rat eye and oral cavity
      epithelia was completed using a standard histological procedure involving the
      avidin-biotin reaction and formation of a brown precipitate with a 3,3'
      diaminobenzidine solution. When examined by affinity chromatography, all lectins
      studied were found to show high percentage biotinylation (i.e. less than 4% by
      weight of total lectin was eluted from the column). The lectin:biotin ratio was
      estimated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS
      PAGE), and ranged between 1:2 (Cratylia floribunda) and 1:10.4 (Canavalia
      brasilensis). As with previous studies, all lectins bound to the mucosal surfaces
      to some extent--the Cratylia floribunda lectin appearing to be the most
      promising, whereas the Dioclea violacea lectin showed comparatively weak binding.
      In all cases, the presence of glucose (the hapten sugar) reduced or eliminated
      binding. It was concluded that glucose-mannose binding sites are present on these
      surfaces, and the lectins from C. floribunda showed a particular affinity for
      these.

PMID- 10892028
TI  - Analytical performance of the Genzyme LipoPro Lp(a) kit for plasma lipoprotein(a)
      cholesterol assay.
AB  - The analytical performance of a new assay for plasma lipoprotein(a)-cholesterol
      (Lp[a]-C) was compared with that of our existing Lp(a) protein assay. The Lp(a)-C
      assay utilises lectin affinity chromatography to isolate intact Lp(a) particles.
      The effect of apo(a) isoform size on this system was assessed and found to be
      negligible. Plasma Lp(a) concentrations measured by both assays were in excellent
      accord in 24 subjects with Lp(a) protein concentrations ranging from 1-65 mg/dL
      (r2 = 0.916). Linearity of the Lp(a)-C assay system was excellent (r2 = 0.997)
      and within-run precision was 6.9% at an Lp(a)-C concentration of 0.3 mmol/L.
      Between-calibration precision was checked and proved to be 7.9%. The lectin
      binding reagent used in the assay bound different sized apo(a) isoforms equally,
      and the recovery of Lp(a) from the reagent was, on average, 64%. We conclude that
      the Lp(a)-C assay system performs well but that further information is required
      on what new information, if any, the assay provides over traditional Lp(a)
      protein measurements by enzyme-linked immunosorbent assay (ELISA) or
      immunoturbidimetry.

PMID- 10892029
TI  - Effects of antimicrobial drugs on human neutrophil-microbe interactions.
AB  - Antimicrobial drugs may influence neutrophil-microbe interactions in several
      ways, and, conversely, neutrophils may interfere with the action(s) of
      antimicrobial drugs. Here, evidence for the existence of such effects is
      evaluated and attention drawn to the problems of in vitro experimentation in this
      area. The review is restricted to those studies that used human neutrophils,
      clinically achievable drug concentrations, and were well designed. Even so, it is
      noted that little attempt has been made to investigate underlying mechanisms. The
      effects of drugs on microbes, which influence neutrophil-microbe interactions,
      such as concentration and the post-antibiotic effect, are considered. The
      penetration of antimicrobial drugs into neutrophils and subsequent intracellular
      activity is discussed and contrasted with observations obtained using
      macrophages. Overall, neutrophil-microbe interactions are complex and difficult
      to dissect, and carefully designed experiments using closely defined conditions
      are required if meaningful results are to be obtained.

PMID- 10892030
TI  - Applications of computer-aided learning in biomedical sciences: considerations in
      design and evaluation.
AB  - Multimedia computer-aided learning (CAL) is an area that has become increasingly
      prevalent in biomedical science. Here we describe the advances that have taken
      place in the computing industry that have led to this trend. We also outline
      areas within the subject of biomedical science that can most benefit from using
      multimedia CAL as a teaching aid. Furthermore, issues concerning the design of
      CAL (i.e. iterative design, structure, development tools) are discussed. As the
      evaluation of CAL is an essential part of the iterative design process, we look
      at new approaches to evaluation that have emerged in response to the superficial
      focus on usability that many evaluations take.

PMID- 10892031
TI  - Is there a case for an initial recruit electrocardiogram?

PMID- 10892032
TI  - Snow Grey--a loan draft and new sea legs.

PMID- 10892033
TI  - Great Britain's ratification of the 1977 Geneva Protocols: greater protection for
      medical personnel in conflict areas at sea and ashore.

PMID- 10892034
TI  - GP 2000: what's happening in general practice?

PMID- 10892035
TI  - Primary blast injury: pathophysiology and implications for treatment. Part III:
      Injury to the central nervous system and the limbs.
AB  - There are some structures in which changes consistent with primary blast may be
      found despite secondary and tertiary blast being the most frequent sources of
      injury. The Central Nervous System for example, especially the brain, is well
      protected yet there are historical and experimental accounts of damage which
      cannot be attributed to secondary or tertiary blast or even air embolism
      resulting from pulmonary disruption. Similarly, analysis and experimental
      simulation of specific skeletal injuries has shown that primary blast alone can
      fracture bones and that it is likely to be responsible for limb avulsions in
      victims exposed to stress waves of sufficiently high intensity.

PMID- 10892036
TI  - Band aid, first aid, lucozade.

PMID- 10892037
TI  - The Naval Medical Service last century and into the millennium.

PMID- 10892038
TI  - Guidelines for giddiness please.

PMID- 10892039
TI  - A six-year old suffering from constipation.

PMID- 10892040
TI  - The common causes of hearing loss in adults.

PMID- 10892041
TI  - Treating nasal polyps.

PMID- 10892042
TI  - Ear barotrauma after flying and diving.

PMID- 10892043
TI  - A rational strategy for the treatment of glue ear.

PMID- 10892044
TI  - Advances in ENT surgery.

PMID- 10892045
TI  - White coat hypertension: what are the implications?

PMID- 10892046
TI  - Eating disorders: a strategic approach.

PMID- 10892047
TI  - Management of acute eyelid conditions.

PMID- 10892048
TI  - Preparing your mind.

PMID- 10892049
TI  - Withdrawing PPIs in practice.

PMID- 10892050
TI  - A mother under pressure asks to be sterilised.

PMID- 10892051
TI  - Managing bloating, flatus and flatulence.

PMID- 10892052
TI  - The important signs in acute abdominal pain.

PMID- 10892053
TI  - The patient with anal problems.

PMID- 10892054
TI  - Ensuring early diagnosis in pancreatic cancer.

PMID- 10892055
TI  - Recurrent abdominal pain in childhood.

PMID- 10892056
TI  - A GP guide to recognising food allergy, intolerance and aversion.

PMID- 10892057
TI  - Key developments in gastroenterology.

PMID- 10892058
TI  - A protocol for deep vein thrombosis.

PMID- 10892059
TI  - Parkinson's: integrating the primary and secondary care guidelines.

PMID- 10892060
TI  - [Prevention of neurological diseases--education, research and legislation].

PMID- 10892061
TI  - [How to solve the crisis of neurological drug therapy? ].

PMID- 10892062
TI  - [Treatment of neurological emergencies].

PMID- 10892063
TI  - [Neurological research today].

PMID- 10892064
TI  - [The biological basis of memory].

PMID- 10892066
TI  - [The renewing drug therapy of epilepsy].

PMID- 10892065
TI  - [Treatment of Alzheimer's disease].

PMID- 10892067
TI  - [Connective tissue and the origin of intracranial arterial aneurysms].

PMID- 10892068
TI  - [Can the symptoms of stroke be limited?].

PMID- 10892069
TI  - [Ataxias and their differential diagnostics].

PMID- 10892070
TI  - [Polyneuropathies].

PMID- 10892071
TI  - [Diabetes and peripheral nervous system].

PMID- 10892072
TI  - [Gene errors in muscular diseases].

PMID- 10892073
TI  - [Evaluation of the dizzy patient--what, where and when?].

PMID- 10892074
TI  - [Tremor].

PMID- 10892075
TI  - [The origin of Parkinson's disease].

PMID- 10892076
TI  - [Drug therapy of Parkinson's disease].

PMID- 10892077
TI  - [Pain and its treatment in patients with terminal cancer].

PMID- 10892078
TI  - [Troglitazone, an insulin action enhancer--a drug of precision to treat adult
      onset diabetes].

PMID- 10892079
TI  - [What information does mismatch negativity registering give us about
      developmental speech and language disorders?].

PMID- 10892080
TI  - [Chronobiological rhythms and their relations to sleep disorders and emotional
      disorders in children].

PMID- 10892081
TI  - [X-linked adrenoleukodystrophy--an explanation for school problems of
      boys,walking problems of men and Addison disease].

PMID- 10892082
TI  - [Locality, profession and variations in sickness absence].

PMID- 10892083
TI  - [Glycemic control in the Finnish diabetic patient].

PMID- 10892084
TI  - [Atrioventricular junctional ablation as a treatment for atrial fibrillation].

PMID- 10892085
TI  - [Hemolytic uremic syndrome--a serious complication of mitomycin treatment].

PMID- 10892086
TI  - [Which macrolide antiobiotic to choose and why?].

PMID- 10892087
TI  - [Acute abdominal pain during pregnancy].

PMID- 10892088
TI  - [A patient with previous myocardial infarction, now work-shy].

PMID- 10892089
TI  - ["What now" column telling lies].

PMID- 10892090
TI  - [Vascular surgery--an European medical specialty].

PMID- 10892091
TI  - [Is surgery of venous disorders a part of general or vascular surgery?].

PMID- 10892092
TI  - [Vascular surgery or an angioradiological procedure?].

PMID- 10892093
TI  - [500 legs too many are amputated in Finland annually].

PMID- 10892094
TI  - [Claudication or critical ischemia?].

PMID- 10892095
TI  - [Pitfalls in peripheral pulse palpation].

PMID- 10892096
TI  - [The vascular laboratory].

PMID- 10892097
TI  - [Visualizing the arteries].

PMID- 10892098
TI  - [Treatment of claudication--words or a knife?].

PMID- 10892099
TI  - [Vascular surgery in order to save the lower limb].

PMID- 10892100
TI  - [When should carotid artery stenosis be operated?].

PMID- 10892101
TI  - [Abdominal aortic aneurysm: an illness increasing in the aging population].

PMID- 10892102
TI  - [Endovascular treatments of arterial diseases].

PMID- 10892103
TI  - [Surgical treatment of chronic venous insufficiency and varicose ulcer].

PMID- 10892104
TI  - [Vascular access].

PMID- 10892105
TI  - [Catastrophic illnesses and vascular surgery].

PMID- 10892106
TI  - [Factors affecting the outcome from vascular surgery].

PMID- 10892108
TI  - [On terminology of vascular surgery].

PMID- 10892107
TI  - [Quality control in vascular surgery. Finnvasc Study Group].

PMID- 10892109
TI  - [Influenza vaccinations--use with care].

PMID- 10892110
TI  - [The pathogenesis of aortic valvular stenosis will soon be known].

PMID- 10892111
TI  - [Treatment of ovarian cancer is still a challenge].

PMID- 10892112
TI  - [Virtual reality in radiology].

PMID- 10892113
TI  - [How do patient and general practioner discuss alcohol?].

PMID- 10892114
TI  - [The effectiveness of breast cancer screening in Finland].

PMID- 10892115
TI  - [Mystery of the blue man: alkaptonuria].

PMID- 10892116
TI  - [Choice of a calcium channel blocker].

PMID- 10892117
TI  - [Diagnostics of lower abdominal pain in a woman ].

PMID- 10892118
TI  - [Variably progressing neurological symptoms].

PMID- 10892119
TI  - [Cancer patient in remission with dizziness and taste blindness].

PMID- 10892121
TI  - [Health economics research].

PMID- 10892120
TI  - [Intoxication and a shadowed area in the chest X-ray].

PMID- 10892122
TI  - [Psychic etiology of constipation in a small child].

PMID- 10892123
TI  - [Assessing musculoskeletal illnesses--clinical diagnosis or diagnosis by machine?
      ].

PMID- 10892124
TI  - [Choosing place of birth plays part in the development of obstetric culture].

PMID- 10892125
TI  - [What is the grammatical Finnish term for "apoptosis"?].

PMID- 10892126
TI  - [Gene therapy of hereditary diseases--where are we now?].

PMID- 10892127
TI  - [Psychiatry under development].

PMID- 10892128
TI  - [Endostatin--light on the treatment of cancer in mice].

PMID- 10892129
TI  - [Multi-resistant bacteria--a new challenge for hospital hygiene].

PMID- 10892130
TI  - [Magnetic resonance imaging improves the diagnostics of upper abdomen].

PMID- 10892131
TI  - [Endogenous defense mechanisms of myocardium].

PMID- 10892132
TI  - [Infertility and ovarian cancer].

PMID- 10892133
TI  - [Treating sleep apnea improves mental performance].

PMID- 10892134
TI  - [Thermal threshold measurement in the assessment of diabetic polyneuropathy].

PMID- 10892135
TI  - [Cerebellar damage caused by phenytoin intoxication].

PMID- 10892136
TI  - [Delirium in a young girl].

PMID- 10892137
TI  - [Indications for the use of granulocyte growth factors].

PMID- 10892139
TI  - [Thrombosis risk during puerperium in a thrombosis-prone woman].

PMID- 10892140
TI  - ["That bullet knew its place..."].

PMID- 10892138
TI  - [From a hint to an error].

PMID- 10892141
TI  - [A stubborn eczema in a patient getting immunosuppressive therapy].

PMID- 10892142
TI  - [A patient with myocardial infarction loosing her sight].

PMID- 10892143
TI  - [Recommended treatment guideline for breast cancer. Finnish Breast Cancer Group].

PMID- 10892145
TI  - [Earth's population prognosis and human carrying capacity].

PMID- 10892144
TI  - [The anamnesis].

PMID- 10892146
TI  - [Continuous growth?].

PMID- 10892149
TI  - [Education and women's position].

PMID- 10892147
TI  - [Can food production keep up with the pace of population growth?].

PMID- 10892148
TI  - [Towards planned reproduction].

PMID- 10892150
TI  - [Ecological ethics].

PMID- 10892151
TI  - [The diseases of the future].

PMID- 10892152
TI  - [Possibilities of altruism].

PMID- 10892153
TI  - [The epicrisis].

PMID- 10892154
TI  - [Santa Claus as a consultant. "Then we together will rejoice, children's eyes
      will shine with joy"].

PMID- 10892155
TI  - [Confusional state of a body builder].

PMID- 10892156
TI  - [The physician registries of our century].

PMID- 10892157
TI  - [Should routines for fetal trisomy screening be changed?].

PMID- 10892158
TI  - [The Nobel prize in medicine for a prion researcher].

PMID- 10892159
TI  - [The Nobel prize in chemistry for researchers of Na+, K+ ATPase and ATP
      synthase].

PMID- 10892160
TI  - [Antibiotic resistance. Will drugs remain effective? Consensus Conference.
      November 17-19, 1997. Espoo, Finland].

PMID- 10892161
TI  - [Fetal nuchal edema and chromosomal defects].

PMID- 10892162
TI  - [Early pregnancy serum screening in Helsinki: results and mothers' opinions].

PMID- 10892163
TI  - [Serum screening in risk pregnancies--experiences and attitudes of mothers living
      in Tampere].

PMID- 10892164
TI  - [Prodrugs].

PMID- 10892165
TI  - [What was it that bit?].

PMID- 10892166
TI  - [The boy's abdominal pain ].

PMID- 10892167
TI  - [Does the interpretation of scientific results depend on who is the reader?].

PMID- 10892168
TI  - [On the effectiveness of physiotherapy].

PMID- 10892169
TI  - [Schizophrenia--a linguistic game of psychiatric diagnostics?].

PMID- 10892170
TI  - [Is schizophrenia a hereditary illness?].

PMID- 10892171
TI  - [Schizophrenia as a fetal developmental disorder of the central nervous system ].

PMID- 10892172
TI  - [What is the age of onset in schizophrenia?].

PMID- 10892173
TI  - [On neuropsychology in schizophrenia].

PMID- 10892174
TI  - [Brain imaging findings in schizophrenia].

PMID- 10892175
TI  - [The changing drug therapy of schizophrenia].

PMID- 10892176
TI  - [The position of psychotherapeutic methods in the treatment of schizophrenia].

PMID- 10892177
TI  - [Hemostatic thrombus, the mechanism for the development of pathological thrombus,
      and platelets].

PMID- 10892178
TI  - [Approach to diagnosis of hemorrhagic diathesis].

PMID- 10892179
TI  - [Indicators for platelet formation (reticulated platelets and thrombopoietin)].

PMID- 10892180
TI  - [Index for platelet activation].

PMID- 10892181
TI  - [Usefulness of bleeding time].

PMID- 10892182
TI  - [Mechanism for production of autoantibody in idiopathic thrombocytopenic
      purpura].

PMID- 10892183
TI  - [Gene analysis of congenital platelet disorders].

PMID- 10892184
TI  - [Arterial thrombosis and polymorphism of platelet membrane glycoprotein genes].

PMID- 10892185
TI  - [Physiopathology and diagnosis of essential thrombocythemia].

PMID- 10892186
TI  - [New development in the treatment of idiopathic thrombocytopenic purpura].

PMID- 10892187
TI  - [Approaches to the treatment of essential thrombocythemia].

PMID- 10892189
TI  - [Recent concept of platelet transfusion].

PMID- 10892188
TI  - [Efficacy of anti-platelet therapy in thrombosis].

PMID- 10892190
TI  - [Thrombotic thrombocytopenic purpura and von Willebrand factor- specific-cleaving
      enzyme].

PMID- 10892191
TI  - [Efficacy of hematopoietic factors in thrombocytopenia].

PMID- 10892192
TI  - [Platelet disorders seen in clinical practice (discussion)].

PMID- 10892193
TI  - [Squamous cell carcinoma of the lung with metastasis to the rectus muscle of
      thigh].

PMID- 10892194
TI  - [Bronchial asthma complicated with mediastinal, epidural emphysema].

PMID- 10892195
TI  - [Left partial anomalous pulmonary venous return to the innominate and hepatic
      veins].

PMID- 10892196
TI  - [High resolution CT findings in two adults with varicella pneumonia].

PMID- 10892197
TI  - [Acute renal failure probably induced by Tamm-Horsfall protein].

PMID- 10892198
TI  - [Analysis of etiology of cardiovascular diseases observed during Hanshin-Awaji
      Earthquake--impact of acute stress in the aging society].

PMID- 10892199
TI  - [Economic analysis of therapeutic actions--fundamental concepts and examples of
      application].

PMID- 10892200
TI  - From the lab to the police station. A successful application of eyewitness
      research.
AB  - The U.S. Department of Justice released the first national guide for collecting
      and preserving eyewitness evidence in October 1999. Scientific psychology played
      a large role in making a case for these procedural guidelines as well as in
      setting a scientific foundation for the guidelines, and eyewitness researchers
      directly participated in writing them. The authors describe how eyewitness
      researchers shaped understanding of eyewitness evidence issues over a long period
      of time through research and theory on system variables. Additional pressure for
      guidelines was applied by psychologists through expert testimony that focused on
      deficiencies in the procedures used to collect the eyewitness evidence. DNA
      exoneration cases were particularly important in leading U.S. Attorney General
      Janet Reno to notice the eyewitness literature in psychology and to order the
      National Institute of Justice to coordinate the development of national
      guidelines. The authors describe their experience as members of the working
      group, which included prosecutors, defense lawyers, and law enforcement officers
      from across the country.

PMID- 10892201
TI  - Resolving the debate over birth order, family size, and intelligence.
AB  - Hundreds of research articles have addressed the relationship between birth order
      and intelligence. Virtually all have used cross-sectional data, which are
      fundamentally flawed in the assessment of within-family (including birth order)
      processes. Although within-family models have been based on patterns in cross
      sectional data, a number of equally plausible between-family explanations also
      exist. Within-family (preferably intact-family) data are prerequisite for
      separating within- and between-family causal processes. This observation reframes
      an old issue in a way that can be easily addressed by studying graphical
      patterns. Sibling data from the National Longitudinal Survey of Youth are
      evaluated, and the results are compared with those from other studies using
      within-family data. It appears that although low-IQ parents have been making
      large families, large families do not make low-IQ children in modern U.S.
      society. The apparent relation between birth order and intelligence has been a
      methodological illusion.

PMID- 10892202
TI  - Psychology and gender at the turn of the century.
AB  - The turn of the 20th century in America was a period of changing gender ideals.
      The younger generation of women pressed for economic independence and political
      rights. Men became caught up with the virility and physicality of the new
      standard of passionate manhood. These gender shifts were reflected in turn-of-the
      century American psychology. With men dominating the discipline, the emerging
      scientific psychology projected the values of the new man. Several examples of
      this androcentric psychology are reviewed, including the views of such prominent
      psychologists as G. Stanley Hall, James McKeen Cattell, and William James. There
      were also a few women psychologists who challenged the androcentric bias by
      attempting to incorporate the values of the new woman, most notably Mary Whiton
      Calkins, Helen Thompson Woolley, and Leta Stetter Hollingworth.

PMID- 10892203
TI  - The first generation of women psychologists and the psychology of women.
AB  - At the end of the 19th century, psychology was among the most hospitable of the
      sciences in admitting women to its ranks. Among this so-called first generation
      of women psychologists were a number of individuals who aggressively challenged
      the prevailing stereotypes concerning the psychological characteristics of women
      and men. Further, many of these women actively promoted equal educational and
      professional opportunities for women.

PMID- 10892204
TI  - Stress and coping research. Methodological challenges, theoretical advances, and
      clinical applications.
AB  - Coping is among the most widely studied topics in contemporary psychology.
      However, the explosion of interest in coping has yielded little and the field is
      in crisis. This section offers a survey of the state of the art in theory and
      research on stress and adaptational processes. The four core articles in the
      section take up, respectively, problems in research design, the neglect of
      unconscious reactions to stress, the selection of adaptational outcomes, and the
      link between research on adaptational processes and clinical practice. The final
      article by Richard S. Lazarus offers a commentary. The present introduction
      provides the historical backdrop for the section. Then, after a brief overview of
      research on adaptational processes, the authors summarize the scope and yield of
      coping research and preview the four core articles in the section. The strengths
      and limits of individual coping efforts and the need for realistic expectations
      and redoubled efforts are discussed.

PMID- 10892205
TI  - A daily process approach to coping. Linking theory, research, and practice.
AB  - For decades, coping researchers have used between-person designs to address
      inherently within-person questions derived from theory and clinical practice. The
      authors describe recent developments in the use of within-person, process
      oriented methods that examine individuals intensively over time. Ongoing studies
      of stress and alcohol consumption, the effects of depression on adaptational
      processes, and the temporal dynamics of coping with chronic pain demonstrate that
      by tracking rapidly fluctuating processes such as mood and coping close to their
      real-time occurrence, daily process designs offer unique insights into
      conceptually and clinically challenging questions. Such designs also provide new
      opportunities to examine the purported mechanisms of therapeutic interventions.
      Despite its demands on participants and investigators, daily process research
      offers fresh opportunities to link psychological theory, research, and practice.

PMID- 10892206
TI  - Defense mechanisms in psychology today. Further processes for adaptation.
AB  - Although the concept of the defense mechanism was rejected from academic
      psychology for a number of years, recent empirical studies show renewed interest
      in defenses. Cognitive psychologists have confirmed the existence of unconscious
      psychological processes, a requisite for defenses. Developmental, personality,
      and social psychologists have all found evidence for defense mechanisms that
      explicate psychological functioning. The relevance of this new information for
      clinical practice is discussed.

PMID- 10892207
TI  - Positive affect and the other side of coping.
AB  - Although research on coping over the past 30 years has produced convergent
      evidence about the functions of coping and the factors that influence it,
      psychologists still have a great deal to learn about how coping mechanisms affect
      diverse outcomes. One of the reasons more progress has not been made is the
      almost exclusive focus on negative outcomes in the stress process. Coping theory
      and research need to consider positive outcomes as well. The authors focus on one
      such outcome, positive affect, and review findings about the co-occurrence of
      positive affect with negative affect during chronic stress, the adaptive
      functions of positive affect during chronic stress, and a special class of
      meaning-based coping processes that support positive affect during chronic
      stress.

PMID- 10892208
TI  - Never the Twain shall meet? Closing the gap between coping research and clinical
      intervention research.
AB  - Two distinct literatures have contributed to a tremendous growth of interest in
      coping. The 1st consists of descriptive studies that have used coping checklists.
      This literature is in crisis because of its failure to yield substantive findings
      concerning the role of coping in adaptation that cannot be dismissed as truisms,
      trivia, or the product of a confounding of stress, coping, and distress. The 2nd
      literature concerns interventions to improve adaptation by enhancing coping. It
      provides evidence of the efficacy of intervention but provides little
      understanding of crucial ingredients, mechanisms of change, or barriers to
      maintaining gains. Both literatures would benefit from cross-fertilization.
      Process studies of interventions designed to improve coping provide an
      alternative to fruitless and potentially misleading correlational studies using
      checklists. Such studies might also aid in understanding and refining
      intervention strategies.

PMID- 10892209
TI  - Toward better research on stress and coping.
AB  - In commenting in considerable detail on the four main articles in the special
      section on stress and coping, the author comes to two main conclusions: First,
      there is an increasing amount of high quality research on stress and coping that
      suggests the field is finally maturing, and this research may help reduce the
      long-standing gap between research and clinical practice. Second, this research
      is increasingly using badly needed research designs that have not hitherto been
      sufficiently emphasized, such as longitudinal or prospective designs, focused on
      observations that are day-to-day, microanalytic, and in-depth, and that are
      compatible with a holistic outlook. The author also addresses the role of
      positive emotion in coping, the concept of defense as it is dealt with nowadays,
      and the task of evaluating coping efficacy.

PMID- 10892210
TI  - Hans J. Eysenck (1916-1997).

PMID- 10892212
TI  - Ideology trumps social science.

PMID- 10892211
TI  - Frank Joseph McGuigan (1924-1998).

PMID- 10892213
TI  - Not quite right.

PMID- 10892214
TI  - Children need adults, not polemics.

PMID- 10892215
TI  - Reconstructing fathers.

PMID- 10892216
TI  - The article isn't serious.

PMID- 10892217
TI  - Continuing the dialogue about fathers and families.

PMID- 10892218
TI  - Comparing the DISC and the youth self-report.

PMID- 10892219
TI  - Chronic fatigue syndrome.

PMID- 10892220
TI  - Children and adolescents who are sexually abusive of others.

PMID- 10892221
TI  - Recurrent depression: infectious-autoimmune etiology?

PMID- 10892222
TI  - Fluoxetine in the treatment of self-mutilating behavior.

PMID- 10892223
TI  - Review of neuroimaging studies of child and adolescent psychiatric disorders from
      the past 10 years.
AB  - OBJECTIVES: To review recent neuroimaging studies of serious emotional disorders
      in youth and identify problems and promise of neuroimaging in clinical practice.
      METHOD: Published reports from refereed journals are briefly described,
      critiqued, and synthesized into a summary of the findings to date. RESULTS:
      Childhood-onset schizophrenia shows progressive ventricular enlargement,
      reduction in total brain and thalamus volume, changes in temporal lobe
      structures, and reductions in frontal metabolism. Autistic disorder is associated
      with cerebellar changes, greater total brain and lateral ventricle volume, and
      asymmetry. The prefrontal cortex and the basal ganglia are consistently reported
      as abnormal in attention-deficit/hyperactivity disorder. Patients with anorexia
      nervosa show enlarged CSF spaces and reductions in gray and white matter that are
      only partially reversible with weight recovery. CONCLUSIONS: Results from
      neuroimaging studies of childhood-onset psychiatric disorders suggest consistency
      in the structures found to be abnormal, but inconsistencies in the nature of
      these abnormalities. Although neuroimaging technology holds great promise for
      neurodevelopmental research, it is not yet a diagnostic instrument.

PMID- 10892224
TI  - The victimization of children: recommendations for assessment and instrument
      development.
AB  - The study and treatment of juvenile victimization would greatly benefit from
      instruments that are comprehensive, methodologically sound, and relevant to
      settings such as health and mental health clinics, criminal justice institutions,
      and child protection agencies. Toward these ends, this article makes 20
      recommendations. Among other things, instruments should (1) allow victimization
      to be mapped onto conventional crime and child protection system categories; (2)
      adequately assess victimization by family and other nonstranger perpetrators; (3)
      ask about crimes specific to childhood, such as nonviolent sexual offenses and
      neglect; (4) allow for comparisons between juvenile and adult victimizations; (5)
      collect self-report data with children as young as age 7 years; (6) use simple,
      behaviorally specific language; (7) protect privacy during data collection; (8)
      attend to potential ethnic, class, and gender differences; and (9) prepare
      procedures to assist children in danger. Comprehensive and well-researched
      instrumentation could greatly advance the study and treatment of juvenile
      victimization.

PMID- 10892225
TI  - Mental health in pediatric settings: distribution of disorders and factors
      related to service use.
AB  - OBJECTIVES: To examine child psychiatric disorders in pediatric settings and
      identify factors associated with parents' use of pediatricians as resources
      concerning emotional/behavioral issues and use of mental health services. METHOD:
      The sample consists of 5- to 9-year-olds (mean = 7.17 years, SD = 1.41) from a
      representative sample (N = 1,060) of pediatric practices. Parent interviews
      included assessments of psychiatric disorders with the Diagnostic Interview
      Schedule for Children (DISC-R), parental depression/anxiety, possible child
      abuse, stress, support, and the use of mental health services. RESULTS: The
      prevalence of any DISC disorder was 16.8%. Parental depression/anxiety and
      possible child abuse were associated independently with 2- to 3-times higher
      rates of disorder. Many parents (55%) who reported any disorder did not report
      discussing behavioral/emotional concerns with their pediatrician. Factors
      associated with discussing behavioral/emotional issues were the presence of any
      disorder and financial stress. Factors related to seeing a mental health
      professional were discussing behavioral/emotional issues with the pediatrician,
      single parenthood, and stressful life events. CONCLUSIONS: The prevalence rates
      of disorders in this setting suggest that pediatricians are well-placed to
      identify and refer children with psychiatric disorders. However, most parents do
      not discuss behavioral/emotional issues with their pediatrician. Methods for
      improving rates of identification and referral (e.g., routine screening) are
      considered.

PMID- 10892226
TI  - Continuity and change of psychopathology from childhood into adulthood: a 14-year
      follow-up study.
AB  - OBJECTIVE: To test the 14-year continuity and change of behavioral and emotional
      problems from childhood into adulthood. METHOD: For 1,615 children and
      adolescents aged 4 to 16 years from the general population, parents completed the
      Child Behavior Checklist (CBCL) at initial assessment. At follow-up 14 years
      later, subjects completed the Young Adult Self-Report (YASR), and their parents
      completed the Young Adult Behavior Checklist (YABCL). RESULTS: Of the subjects
      who were initially classified as deviant, 14 years later 41% were classified as
      deviant according to their YABCL Total Problem score, and 29% according to their
      YASR Total Problem score. Intrainformant (CBCL/YABCL) Withdrawn, Social Problems,
      Delinquent Behavior, and Aggressive Behavior scores, and cross-informant
      (CBCL/YASR) Anxious/Depressed, Thought Problems, and Delinquent Behavior scores
      were independent predictors of general levels of problem behavior. CONCLUSIONS:
      Childhood and adolescent problems persisted to a considerable degree into
      adulthood, although the majority of children who were deviant at initial
      assessment could not be regarded as deviant 14 years later. Children who were
      adolescents at initial assessment (12-16 years) showed higher stability of
      problem behaviors than subjects who were children at initial assessment (4-11
      years).

PMID- 10892227
TI  - Early attention problems and children's reading achievement: a longitudinal
      investigation. The Conduct Problems Prevention Research Group.
AB  - OBJECTIVES: To determine whether attention problems predict the development of
      reading difficulties and examine whether screening for attention problems could
      be of practical value in identifying children at risk for reading
      underachievement. METHOD: Three hundred eighty-seven children were monitored from
      kindergarten through fifth grade. Standardized assessments of attention problems
      and reading achievement were conducted at multiple time points. RESULTS:
      Attention problems predicted reading achievement even after controlling for prior
      reading achievement, IQ, and other behavioral difficulties. Inattentive first
      graders with normal reading scores after kindergarten were at risk for poor
      reading outcomes. CONCLUSIONS: Attention problems play an important role in the
      development of reading difficulties for some children, and screening for
      attention problems may help identify children at risk for reading difficulties.

PMID- 10892228
TI  - Young suicide attempters: a comparison between a clinical and an epidemiological
      sample.
AB  - OBJECTIVE: To compare risk factors for self-harm in 2 groups: hospitalized
      adolescents who had attempted suicide and adolescents reporting suicide attempts
      in a community survey. METHOD: All suicide attempters aged 13 to 19 years
      admitted to medical wards (n = 91) in a region of Norway were assessed and
      interviewed. Risk factors were identified by comparisons with a general
      population sample participating in a questionnaire study in the same community (n
      = 1,736). In this population sample, a separate analysis of risk factors for
      reporting deliberate self-harm (n = 141) was performed, applying bivariate and
      multivariate logistic regression models. RESULTS: Adjusted risk factors for
      suicide attempts in hospitalized adolescents were depression (odds ratio [OR] =
      4.7), disruptive disorders (OR = 9.4), low self-worth (OR = 1.3), infrequent
      support from parents (OR = 3.3) or peers (OR = 3.3), parents' excessive drinking
      (OR = 4.3), and low socioeconomic status (OR = 2.4). For adolescents who self
      reported self-harm, depression (OR = 3.1) and loneliness (OR = 1.13) were
      significant adjusted risk factors (p < .001). Low self-worth, low socioeconomic
      status, and little support from parents or peers characterized hospitalized
      suicidal adolescents compared with those who were not hospitalized. CONCLUSIONS:
      The risk factors were more powerful for hospitalized than for nonhospitalized
      adolescents. Prevention efforts should target the same factors for both groups,
      at a population level for nonhospitalized adolescents and at an individual level
      for hospitalized adolescents, with a focus on depression, low self-esteem, and
      family communication.

PMID- 10892229
TI  - Parameters of suicidal crises vary as a function of previous suicide attempts in
      youth inpatients.
AB  - OBJECTIVES: Although suicidal crises demand an enormous amount of clinical
      attention, surprisingly little empirical research has been conducted on the
      parameters of suicidal crises in general, and in children and adolescents in
      particular. On the basis of past conceptual work on the unique characteristics of
      multiple suicide attempters, as well as work on the effect of previous suicidal
      and depressive experience on later functioning, the authors developed predictions
      regarding the intensity and duration of suicidal crises in youths presenting to
      inpatient psychiatry units. Specifically, it was hypothesized that multiple
      attempt status would relate significantly to intensity of suicidal crises and
      would relate more strongly to intensity than to duration of crises. METHOD: Data
      on past suicide history and self-rated symptoms were collected for 50 suicidal
      patients, all of whom were available at follow-up. RESULTS: Findings conformed to
      prediction: Multiple attempters experienced more intense but not more long
      lasting crises; the relation between multiple attempt status and crisis intensity
      exceeded that between multiple attempt status and crisis duration. CONCLUSIONS:
      Previous suicidal experience may alter the parameters of current suicidal crises.
      Implications of these findings for suicide risk and clinical assessment and
      management are discussed.

PMID- 10892231
TI  - The OADP-CDS: a brief screener for adolescent conduct disorder.
AB  - OBJECTIVES: To examine the ability of a very brief (6-item) self-report screener,
      the Oregon Adolescent Depression Project Conduct Disorder Screener (OADP-CDS), to
      identify adolescents with a lifetime diagnosis of conduct disorder and to examine
      its ability to predict antisocial personality disorder by age 24. Relevant scales
      from the Yough Self-Report and the Child Behavior Checklist were examined for
      comparison purposes. METHOD: A total of 1,709 high school students completed an
      initial questionnaire and diagnostic interview assessment (T1); 1,507
      participants returned approximately 1 year later for a second assessment (T2). A
      third (T3) assessment was conducted with selected T2 participants (n = 940) after
      they had turned 24 years of age. RESULTS: The OADP-CDS had good internal
      consistency, test-retest stability, and screening properties. Differences in the
      screening ability of the OADP-CDS as a function of gender and social desirability
      were nonsignificant. The efficacy of the measure as a screener did not differ
      significantly from that of longer adolescent- and parent-report measures. Perhaps
      most importantly, the OADP-CDS was able to identify future cases of antisocial
      personality disorder in young adulthood. CONCLUSIONS: Results suggest that self
      report screening for conduct disorder with older adolescents is possible and
      should be explored further.

PMID- 10892230
TI  - Risk behavior in a community sample of children and adolescents.
AB  - OBJECTIVES: First, to investigate whether there is covariation between risk
      behaviors, including suicidality, in a community probability sample of children
      and adolescents; and second, to investigate whether risk behavior is associated
      with selected potential correlates. METHOD: A sample of 9- to 17-year-old youths
      (N = 1,285) and their caretakers were interviewed in the Methods for the
      Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. The risk
      behaviors were marijuana smoking, alcohol use, intercourse, fighting, cigarette
      smoking, and suicidal ideation/attempts. Relationships between the risk behaviors
      were described using odds ratios. Linear regression analyses of an index of risk
      behavior on the selected potential correlates of risk behavior were conducted.
      RESULTS: There were significant relationships between all pairs of risk
      behaviors. The score on the index of risk behavior was associated with stressors,
      lack of resources, family psychiatric disorder, psychopathology, and functional
      impairment. CONCLUSIONS: Clinicians should be alerted to the possibility of risk
      behaviors, especially in children and adolescents engaging in other risk
      behaviors and those with inadequate resources, stressors, functional impairment,
      or psychopathology.

PMID- 10892232
TI  - Behavioral and emotional problems in Chinese children of divorced parents.
AB  - OBJECTIVE: This study examined the behavioral problems in Chinese children of
      divorced parents. METHOD: A total of 58 children of divorce and 116 gender-, age
      , and school class-matched controls were ascertained from a general population
      sample of children aged 6 through 15 years. Parents completed the Child Behavior
      Checklist (CBCL), and teachers completed the Teacher's Report Form (TRF) and
      Conners Hyperkinesis Index. RESULTS: Parent-reported problem scores on the CBCL
      total scale and each subscale, and prevalence of all CBCL syndromes except for
      Somatic Complaints, were significantly higher in children of divorce than in
      controls. Teacher-reported problem scores on the TRF total scale and Social and
      Attention Problems and prevalence of Attention Problems were significantly
      different for the 2 groups of children. Social competence was rated significantly
      lower in children of divorce than in controls. Discriminant function analysis
      showed that behavioral problems in children of divorce were characterized by
      aggressive behavior, withdrawal, and social problems. CONCLUSIONS: The findings
      emanating from China provide the first evidence of the link between parental
      divorce and children's psychopathology and clarify the psychopathological
      dimensions in Chinese children of divorced parents.

PMID- 10892233
TI  - Case study: Exposure and response prevention for an adolescent with Tourette's
      syndrome and OCD.
AB  - Using recently refined diagnostic criteria, the authors hypothesized that the
      frequent touching of others by a 16-year-old male adolescent with Tourette's
      syndrome was a compulsion and not a tic. Consistent with the study's hypothesis,
      the authors applied exposure and response prevention, a procedure empirically
      supported for treatment of compulsions but not for tics, to the touching. Results
      showed a significant decrease in touching attempts, overt anxiety, and subjective
      anxiety across time.

PMID- 10892234
TI  - The Texas Children's Medication Algorithm Project: Report of the Texas Consensus
      Conference Panel on Medication Treatment of Childhood Attention
      Deficit/Hyperactivity Disorder. Part I. Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVES: Expert consensus methodology was used to develop evidence-based,
      consensually agreed-upon medication treatment algorithms for attention
      deficit/hyperactivity disorder (ADHD) in the public mental health sector.
      Although treatment algorithms for adult mental disorders have been developed,
      this represents one of the first attempts to develop similar algorithms for
      childhood mental disorders. Although these algorithms were developed initially
      for the public sector, the goals of this approach are to increase the uniformity
      of treatment and improve the clinical outcomes of children and adolescents with
      ADHD in a variety of treatment settings. METHOD: A consensus conference of
      academic clinicians and researchers, practicing clinicians, administrators,
      consumers, and families was convened to develop evidence-based consensus
      algorithms for the pharmacotherapy of childhood ADHD. After a series of
      presentations of current research evidence and panel discussion, the consensus
      panel met and drafted the algorithms along with guidelines for implementation.
      RESULTS: The panel developed consensually agreed-upon algorithms for ADHD with
      and without specific comorbid disorders. The algorithms consist of systematic
      strategies for psychopharmacological interventions and tactics to ensure
      successful implementation of the strategies. While the algorithms focused on the
      medication management of ADHD, the conference emphasized that psychosocial
      treatments are often a critical component of the overall management of ADHD.
      CONCLUSIONS: Medication algorithms for ADHD can be developed with consensus. A
      companion article will discuss the implementation of these algorithms.

PMID- 10892235
TI  - The Texas Children's Medication Algorithm Project: Report of the Texas Consensus
      Conference Panel on Medication Treatment of Childhood Attention
      Deficit/Hyperactivity Disorder. Part II: Tactics. Attention-Deficit/Hyperactivity
      Disorder.
AB  - OBJECTIVES: Expert consensus methodology was used to develop a medication
      treatment algorithm for attention-deficit/hyperactivity disorder (ADHD). The
      algorithm broadly outlined the choice of medication for ADHD and some of its most
      common comorbid conditions. Specific tactical recommendations were developed with
      regard to medication dosage, assessment of drug response, management of side
      effects, and long-term medication management. METHOD: The consensus conference of
      academic clinicians and researchers, practicing clinicians, administrators,
      consumers, and families developed evidence-based tactics for the pharmacotherapy
      of childhood ADHD and its common comorbid disorders. The panel discussed
      specifics of treatment of ADHD and its comorbid conditions with stimulants,
      antidepressants, mood stabilizers, alpha-agonists, and (when appropriate)
      antipsychotics. RESULTS: Specific tactics for the use of each of the above agents
      are outlined. The tactics are designed to be practical for implementation in the
      public mental health sector, but they may have utility in many practice settings,
      including the private practice environment. CONCLUSIONS: Tactics for
      psychopharmacological management of ADHD can be developed with consensus.

PMID- 10892236
TI  - Evaluating and reporting emotional abuse in children: parent-based, action-based
      focus aids in clinical decision-making.

PMID- 10892237
TI  - Genetics of childhood disorders: XVI. Angelman syndrome: a failure to process.

PMID- 10892238
TI  - Proceedings of the 3rd International Working Conference on Biosignal
      Interpretation (BSI99). Chicago, Illinois, USA. June 12-14, 1999.

PMID- 10892239
TI  - Trend recognition in clinical signals using template-based methods.
AB  - The recognition of clinically significant trends in monitored signals plays an
      important role in many medical diagnostic applications. A template-based system
      technique to identify characteristic patterns in time-series data is described,
      based on fuzzy logic. Fuzzy set theory allows the creation of fuzzy templates
      from linguistic rules. The resulting fuzzy template system can accommodate
      multiple time signals, relative or absolute trends, and automatically generates a
      normalised "goodness of fit" score. The template approach was originally
      developed for monitoring during anaesthesia but has the potential to be useful in
      other domains that require temporal pattern recognition.

PMID- 10892240
TI  - Computational model of DIC microscopy for reconstructing 3-D specimens.
AB  - Differential Interference Contrast (DIC) microscopy is a powerful visualization
      tool used to study live biological cells. Its use, however, has been limited to
      qualitative observations. The inherent non-linear relation between the object
      properties and the image intensity makes quantitative analysis difficult. As a
      first step towards measuring optical properties of objects from DIC images, we
      develop a model for the image formation process using methods consistent with
      energy conservation laws. We verify our model by comparing real image data of
      manufactured specimens to simulated images of virtual objects. As the next step,
      we plan to use this model to reconstruct the three-dimensional properties of
      unknown specimens.

PMID- 10892241
TI  - EEG/MEG error bounds for a dynamic dipole source with a realistic head model.
AB  - This work presents the background and derivation of Cramer-Rao bounds on the
      errors of estimating the parameters (moment and location) of a dynamic current
      dipole source using data from electro- and magneto-encephalography. A realistic
      head model, based on knowledge of surfaces separating tissues of different
      conductivities, is used.

PMID- 10892242
TI  - Time series and the dynamics of demand pacing.
AB  - Motivated by a common practice in cardiology, we analyze the dynamics of a demand
      paced system where one seeks to create a stable periodic response. By using
      techniques originally developed for controlling chaotic systems, one can enhance
      the information contained in time series regarding hidden, unstable periodic
      orbits. This makes it possible, for example, to track drifts in a system's
      dynamics.

PMID- 10892243
TI  - Bifurcation in a simple model of the cardiovascular system.
AB  - A simple nonlinear beat-to-beat model of the human cardiovascular system has been
      studied. The model, introduced by DeBoer et al. was a simplified linearized
      version. We present a modified model which allows to investigate the nonlinear
      dynamics of the cardiovascular system. We found that an increase in the alpha
      sympathetic gain, via a Hopf bifurcation, leads to sustained oscillations both in
      heart rate and blood pressure variables at about 0.1 Hz (Mayer waves). Similar
      oscillations were observed when increasing the beta-sympathetic gain or
      decreasing the vagal gain. Further changes of the gains, even beyond reasonable
      physiological values, did not reveal another bifurcation. The dynamics observed
      were thus either fixed point or limit cycle. Introducing respiration into the
      model showed entrainment between the respiration frequency and the Mayer waves.

PMID- 10892244
TI  - Neurologial interpretations and the information in the cognitive pupillary
      response.
AB  - It has been known for 70 years that the human pupil dilates when a person
      responds to a cognitive task. Further, it is known that parasympathetic pupillary
      innervation decreases with raised attention state while sympathetic innervation
      increases. But the information the pupil transmits during elevated attention
      states about such neurological dynamics and a quantitative measure of this
      information have defied statistical modelling. Now we describe experiments using
      a short-term memory task called an acoustic impulse test in which the pupillary
      dynamics in response to random acoustic impulses are recorded with a high
      resolution (0.01 mm) pupillometer with the result that parasympathetic and
      sympathetic pupillary dilation components are quantifiable, as is the information
      transmitted by these components.

PMID- 10892245
TI  - Non-stationary myoelectric signals and muscle fatigue.
AB  - A mathematical derivation for the mean frequency of a myoelectric signal (MES) is
      provided based on an amplitude modulation model for non-stationary MES. With this
      derivation, it is shown that mean frequency estimates of stationary and non
      stationary myoelectric signals theoretically are not significantly different in a
      physiologically practical context. While this prediction is confirmed via a
      computer simulation, it is refuted with empirical evidence. Regardless, it is
      shown in a final study that mean frequency is capable of tracking a downward
      shift in the power spectrum with fatigue even in non-stationary myoelectric
      signals.

PMID- 10892246
TI  - Band-suppressed restoration of X-ray images blurred by body movement.
AB  - The restoration of X-ray images that have been blurred due to body movement are
      discussed. The observation system for these images is described using a
      mathematical model, and several restoration filters composed of a series of such
      models are proposed. These filters restore band-suppressed approximations of the
      original images. In addition, redundancy is introduced into these restoration
      filters in order to suppress additive noise. These filters are expanded to be
      applicable not only to parallel translations, but also to rotations by coordinate
      transformation. The proposed methods are applied to blurred X-ray images of a
      bone model of the elbow joint. The parameters of the restoration filter are
      estimated using a marker attached to the subject as a reference signal.

PMID- 10892247
TI  - A network inversion technique for estimating equivalent dipole description of
      visual evoked potential.
AB  - For the activation study of the brain, dipole localization from the scalp
      potential is one of the most promising techniques to realize a reasonable
      temporal resolution which cannot be realized in functional MR and PET. The goal
      of our study is to estimate inversely the electrical brain activity in the form
      of several dipoles from the scalp potential, using a network inversion technique.
      As a basic approach, we have inversely estimated several dipoles from the
      potential distribution on a spherical surface, in the homogeneous sphere model.
      In the training phase, by expanding the neural network input dimensions being
      redundant, the network can easily learn the forward mapping. In the inversion
      phase, the space of the expanded-network-input-vector can be narrowed by
      introducing a penalty term. Additionally, a consensus term was used to force
      several dipoles to have a similar orientation. We estimate that this is
      applicable to the localization of several dipoles that reflect the actual brain
      activity, especially in the visual evoked potentials.

PMID- 10892248
TI  - Estimation of scale factors in presence of multiple signals: application to sEMG
      analysis.
AB  - When several realizations of an unknown recurrent signal are observed apart from
      a time expansion or compression, the classical way of estimating these time
      scaling factors is to take one signal as reference for the estimation. This
      approach does not take into account the common information between all possible
      couples of realizations. To achieve this task we use a Maximum-Likelihood based
      method, in a sub-optimal manner. Using some realistic assumptions and
      simplifications, we propose a tractable solution. The improvement of classical
      results is shown through a simulation whose conclusion is that the larger the
      number of realizations, the more correct the estimation. Finally, we apply the
      method to electrically evoked sEMG.

PMID- 10892249
TI  - Spontaneous fluctuations of human pupil reflect central autonomic rhythms.
AB  - Aim of this study is to assess whether and to what extent LF and HF rhythms
      contribute to spontaneous pupil diameter fluctuations at rest and during
      sympathetic activation by Head-Up Tilt Test 70 degrees. ECG, Finapres and
      Respiration data from 10 normal subjects were recorded simultaneously to
      spontaneous pupil diameter fluctuations (SPDF). The respiratory rhythm and the LF
      component were clearly detected in all the SPDF series. The cross-spectrum
      analysis gave significant results (> 0.5) in HF band. During tilt, a reduction in
      the total variability with a relative increase of the LF component was observed
      in HR, BP and SPDF signals. The multivariate analysis of the SPDF and of the
      cardiovascular variability series allows new insights into the physiology of
      pupil neural control. The effect of tilting on SPDF spectra and the physiological
      background of the pupil control are consistent with the hypothesis that pupil
      fluctuations reflect a generalized increase of the sympathetic tone.

PMID- 10892250
TI  - Reconstructing bifurcation diagrams of dynamical systems using measured time
      series.
AB  - We present an algorithm for reconstructing the bifurcation structure of a
      dynamical system from time series. The method consists in finding a parameterized
      predictor function whose bifurcation structure is similar to that of the given
      system. Nonlinear autoregressive (NAR) models with polynomial terms are employed
      as predictor functions. The appropriate terms in the NAR models are obtained
      using a fast orthogonal search scheme. This scheme eliminates the problem of
      multiparameter optimization and makes the approach robust to noise. The algorithm
      is applied to the reconstruction of the bifurcation diagram (BD) of a neuron
      model from the simulated membrane potential waveforms. The reconstructed BD
      captures the different behaviors of the given system. Moreover, the algorithm
      also works well even for a limited number of time series.

PMID- 10892251
TI  - Theoretical analysis of a rectifying gap junction model.
AB  - Based on the experimental observations, an electrical circuitry model for a
      rectifying gap junction was developed in previous work. In order to show the
      physiological function for each element in the model, a theoretical analysis is
      carried out in this report. The results indicate that the gap junctional
      capacitance Cj newly introduced into the model plays a major role in determining
      the duration increase, the peak attenuation, and the peak delay on the
      postmembrane action potential. Also, a comparison between the newly proposed
      model and the widely accepted kinetic model by Giaume is made. The results show
      that the electrical circuitry model can not only describe the characteristics of
      Giaume's model but also allow the interpretation of some experimental phenomena
      that were not reflected in other gap junctional models.

PMID- 10892252
TI  - Analysis of respiratory sinus arrhythmia with respect to respiratory phase.
AB  - We evaluated the respiratory modulation of heart rate, i.e., respiratory sinus
      arrhythmia (RSA), with respect to respiratory phase derived from an analytic
      signal from the lung volume curve, during spontaneous breathing and paced
      breathing with different patterns. The magnitudes and waveforms of RSA in the
      phase domain were similar regardless of breathing pattern, even including
      spontaneous breathing. An examination of the occurrence of heart beats with
      respect to the respiratory phase revealed that synchronized patterns recently
      reported in the literature (Nature 392: 239, 1998) were observed during paced
      breathing with breath holding periods whereby the respiratory phase advanced more
      slowly. It was concluded that the phase domain approach might be useful in
      extracting RSA during spontaneous breathing and for elucidating detailed
      mechanisms for RSA. However, the use of this technique for studies investigating
      cardio-respiratory coupling should be approached cautiously, as the results may
      be influenced by breathing patterns.

PMID- 10892253
TI  - Heart rate and blood pressure response to short-term head-down bed rest: a
      nonlinear approach.
AB  - Although it is well-known that prolonged exposure to microgravity environment
      such as in space travel results in derangements of orthostasis, recent evidence
      suggests that even short-term exposure may have similar effects and parallels
      such common examples as prolonged bed rest. Whereas spectral analysis of heart
      rate and systolic blood pressure have been unable to detect changes, we
      hypothesized that nonlinear indexes may be better able to uncover such
      perturbations. Eighteen healthy subjects were exposed to 4-hour head-down tilt,
      and of these, 4 exhibited fainting. Two nonlinear indexes, mutual information and
      recurrence quantification were used to analyze the data. Only recurrence
      quantification was able to detect a "decoupling" of heart rate and systolic blood
      pressure at rest using discriminant analysis (p < 0.05). These results suggest
      that orthostatic intolerance may be due to a decoupling of heart rate from
      systolic blood pressure reflexive activity occurring at rest.

PMID- 10892254
TI  - Event-related brain potentials: laplacian transformation for multichannel time
      frequency analysis.
AB  - During a visual-motor task the movement strategies and the learning processes are
      investigated. A group of 10 normal young volunteers underwent the experiment. The
      EEG signal was recorded through the 10-20 acquisition system during the execution
      of a task after a visual input. Each subject repeated the movement several times
      in three different conditions: i) without knowledge of the performance; ii) with
      visual feedback; iii) with knowledge of the result. The signal was transformed
      through Laplacian operator in order to eliminate the spurious coherence and then
      time-variant coherence was calculated. Different trends of the coherence function
      have been evidenced in subjects learning and not learning the better movement
      strategy. In particular, relations have been found between frontal, central and
      occipital electrodes in medium and high frequency ranges.

PMID- 10892255
TI  - Spatial filtering methods for local activation determination in fractionated
      electrograms from simulated infarcted hearts.
AB  - The purpose of this work is the enhancement of local activation in multiphasic
      extracellular recordings coming from infarcted myocardial tissue and,
      consequently, the distinction of local from distal activation. Deconvolution
      procedures are applied, in the form of spatial filtering, in order to estimate
      transmembrane currents from the extracellular recordings. Simulated data are used
      in order to test the methods. The current source estimates are compared to the
      actual transmembrane currents and to Laplacian estimates.

PMID- 10892256
TI  - Differentiation of physiological states under sensory deprivation.
AB  - We attempt to differentiate the physiological state during sensory deprivation
      (SD) from normal sleep and wakefulness in terms of electroencephalogram (EEG) and
      heart rate variability (HRV) dynamics. Kullback-Leibler (K-L) divergence is
      employed to quantify differences between their state-dependent dynamics. As a
      result, the dynamics of EEG and HRV during SD are found to be far distant from
      any representative dynamics of natural states of sleep and wakefulness. However,
      relatively speaking, the findings in SD can be categorized into two patterns. (a)
      The dynamics of HRV during SD is similar to that of rapid eye movement (REM)
      sleep, and the dynamics of EEG during SD is similar to that of wakefulness. (b)
      The dynamics of both HRV and EEG during SD are similar to that of REM. Such
      dissociation between states classified by EEG and HRV dynamics frequently takes
      place during SD. These findings suggest the peculiarity of the physiological
      state during the SD distinct from sleep and wakefulness.

PMID- 10892257
TI  - Injury detection for central nervous system via EEG with higher order crossing
      based methods.
AB  - Higher order crossing (HOC) is a powerful tool for time series analysis. Two HOC
      based EEG analysis methods are developed for brain injury detection and
      quantification. The first method explores EEG spectrum characteristics via an
      estimate of the dominant frequency of a pre-processed EEG signal. The second
      method is based on the norm of the AHOC, an HOC obtained from the alpha-filter
      prefiltered EEG signal. Both methods are shown to be effective in detecting
      hypoxic/asphyxic injuries as well as assessing the severity of the injury.

PMID- 10892258
TI  - Quantitative blood velocity mapping in glomerular capillaries by in vivo
      observation with an intravital videomicroscope.
AB  - We have evaluated rat glomerular microcirculation under in-vivo condition with an
      intravital videomicroscope. To measure erythrocyte velocities, a line segment was
      set along the glomerular capillaries in time-sequential videotaped images and
      then a spatiotemporal image was constructed along that segment. The angle of
      striped pattern in the spatiotemporal image which reflects the erythrocyte
      velocity, was estimated to compute erythrocyte velocity vector mapping. We found
      that erythrocyte velocities in rat glomeruli were significantly faster in
      diabetic rats than in control rats (p < 0.05). In conclusion, we have succeeded
      in quantitatively evaluating the in-vivo renal microcirculation with our
      videomicroscope system and by spatiotemporal image analyzing method.

PMID- 10892259
TI  - Integration of high resolution EEG and functional magnetic resonance in the study
      of human movement-related potentials.
AB  - Cortical sources of human movement-related potentials (i.e. unilateral finger
      extension) were modeled using functional magnetic resonance imaging (fMR) data as
      a constraint of a linear inverse source estimation from highly sampled (128
      channels) EEG data. Remarkably, this estimation was performed within realistic
      subject's MR-constructed head models by boundary element techniques. An
      appropriate figure of merit served to set the optimal amount of fMR constraints.
      With respect to standard linear inverse source estimates, fMR-constrained ones
      presented increased spatial detail and provided a more reliable timing of
      activation in bilateral sensorimotor cortical regions of interest.

PMID- 10892260
TI  - Analysis of acceleration signals using wavelet transform.
AB  - In this study, we attempted to discriminate the acceleration signal for
      horizontal level and stairway walking using wavelet-based fractal analysis
      method. The acceleration signal was measured close to the center of gravity of
      the body, while the subjects walked continuously in the corridor and up and down
      the stairs. We used the wavelet-based fractal analysis method to discriminate
      walking pattern. The parameter H which is related directly to the fractal
      dimension was estimated by the wavelet coefficient and was changed into low value
      during walking upstairs. By manually setting the threshold level for individual,
      it was possible to discriminate walking upstairs from the other walking type.
      However, the common feature among subjects was not shown between level walking
      and walking downstairs.

PMID- 10892261
TI  - Spatio-temporal nonlinear modeling of gastric myoelectrical activity.
AB  - The accomplishment of a complete digestive process of human stomach is regulated
      by a spatio-temporally-coordinated electric pattern called gastric myoelectrical
      activity (GMA). The normal patterns of GMA present temporal evolution from
      endogenous rhythmic oscillation to bursting of spikes associated with
      contractions, and also ordered spatial propagation of the oscillating waves. The
      abnormal patterns of GMA have been observed in temporal dysrhythmia, such as
      tachygastria, bradygastria and arrhythmia, and in spatial propagation failure,
      such as retrograde propagation and uncoupling. Different GMA patterns are
      associated with different gastric symptoms and there exist some nonlinear
      mechanisms to govern the formation and dynamic evolution of these patterns.
      However, these mechanisms are so complex that few of them are known by medical
      observations. The aim of this study is to explore these mechanisms by spatio
      temporal modeling of GMA. The single-cell model simulating the formation process
      of slow waves and spikes, the multi-cell model simulating the propagation process
      of GMA and the extracellular model simulating the formation of bipolar recordings
      are presented.

PMID- 10892262
TI  - Simulation evaluation of cardiac assist devices.
AB  - During past decades, various cardiac assist devices were invented. These cardiac
      assist devices can be classified into two categories: parallel connected or
      sequentially connected to the natural heart. In the past, more attention was paid
      to the assistance of the device provided to the failing heart and most research
      was conducted towards that goal. While less attention was paid to the "dose" of
      the assistance for rehabilitation of the natural heart. In our study, the
      hemodynamic effects of parallel as well as sequential cardiac assist devices are
      investigated in terms of the working load to the natural heart, and the oxygen
      supply and consumption of the natural heart. Preliminary results show that the
      sequential assistance could reduce the working load of the natural heart as well
      as increase the coronary flow. The results also indicate that the control scheme
      of the cardiac assist device has effect on the oxygen supply and consumption of
      the natural heart. There is optimal "dose" of assistance for the rehabilitation
      of the natural heart.

PMID- 10892263
TI  - Simulation of body surface Laplacian maps during ventricular pacing in a 3D
      inhomogeneous heart-torso model.
AB  - A computer simulation study has been conducted to investigate the performance of
      body surface Laplacian maps (BSLMs) in localizing and imaging spatially separated
      myocardial electrical events. A cellular automaton model of ventricles simulates
      cardiac electrical activity using a two-site pacing protocol to induce dual
      simultaneously active myocardial electrical events. The heart model is embedded
      in a realistically shaped inhomogeneous volume conductor. The BSLMs are
      numerically computed from the induced electrical activity in the heart model. The
      present computer simulation results show that the BSLM can provide better
      separation and localization of two regional myocardial electrical events as
      compared with the body surface potential map (BSPM).

PMID- 10892264
TI  - Heart rate signal decomposition.
AB  - This paper proposes a method for decomposing heart rate fluctuations into
      background, respiratory and blood pressure oriented fluctuations. A signal
      cancellation scheme using the adaptive RLS algorithm has been introduced for
      cancelling respiration and blood pressure oriented changes in the heart rate
      fluctuations. The computer simulation confirmed the validity of the proposed
      method. Then, heart rate fluctuations, instantaneous lung volume and blood
      pressure changes are simultaneously recorded from eight normal subjects aged 20
      24 years. It was shown that after signal decomposition, the power spectrum of the
      heart rate showed a consistent monotonic 1/fa type pattern. The proposed method
      enables a clear interpretation of heart rate spectrum removing uncertain large
      individual variations due to the respiration and blood pressure change.

PMID- 10892265
TI  - Immediate surgery reduces mortality in deeply comatose patients with spontaneous
      cerebellar hemorrhage.
AB  - Cerebellar hemorrhage is regarded as a neurosurgical emergency. However, patients
      with deteriorating consciousness are very likely to die irrespective of the
      choice of therapy, and it is not clear if surgical intervention can benefit
      patients in a deeply comatose state. We reviewed 20 patients with a Glasgow Coma
      Scale score of 3 at admission to ascertain the salvage rate and determine the
      prognostic factors. Four patients who were managed conservatively died within 2
      days. Sixteen patients underwent decompressive suboccipital craniectomy and
      hematoma evacuation. At discharge, three patients were moderately disabled, three
      were severely disabled, four were persistently vegetative, and six had died. The
      overall mortality was 50%. The mean interval between the onset of symptoms and
      the operation was 1.67 +/- 0.29 hours in patients with favorable outcome, and
      significantly longer at 2.42 +/- 0.49 hours in patients with an unfavorable
      outcome (p = 0.025). Immediate evacuation of the hematoma reduces morbidity and
      mortality even in deeply comatose patients, especially if the time interval
      between the onset and surgery is within 2 hours.

PMID- 10892266
TI  - Prolapsing gyrus rectus as a cause of progressive optic neuropathy.
AB  - The pathogenesis of optic neuropathy caused by neurovascular compression or by
      similar mechanisms is unclear. Thin-slice magnetic resonance (MR) imaging was
      performed in 69 patients with optic neuropathy without demonstrable
      ophthalmological lesions (57.0 +/- 17.1 years of age) and 102 normal subjects
      (57.7 +/- 13.9 years of age). The MR imaging features were classified into "no
      compression" by the internal carotid artery (ICA), "compression" by the ICA, "no
      contact" with the anterior cerebral artery (ACA) or the gyrus rectus, "contact"
      with either or both, "compression" by the ACA, and "compression" by the gyrus
      rectus. The Spearman correlation coefficients were calculated between patients or
      controls, the MR classification, and the age, and the number of patients in each
      MR classification were evaluated by the chi 2 test. Five of the 69 patients with
      rapidly progressive symptoms were operated on via the frontotemporal approach.
      The MR imaging feature of "compression" by the gyrus rectus was the best
      predictor of optic neuropathy (Spearman correlation coefficients rho = -0.23646,
      p < 0.0018). This MR imaging feature was observed in 38 of 69 patients and in 32
      of 102 controls (p = 0.002). Compression of the nerve by the gyrus rectus or the
      ACA was confirmed in all five operated cases. Decompression of the nerve was
      fully achieved in four of the five patients, and their symptoms have not
      progressed since then. Optic neuropathies due to compression by the prolapsing
      gyrus rectus are not well understood. Such neuropathies may be detected by MR
      imaging.

PMID- 10892267
TI  - Embolic cerebellar infarction caused by spontaneous dissection of the
      extracranial vertebral artery--two case reports.
AB  - Spontaneous dissection of the extracranial vertebral artery (VA) may cause
      ischemic stroke in the posterior circulation. A 22-year-old female and a 38-year
      old male presented with sudden onset of vertigo and nausea without trauma.
      Angiography was initially interpreted as normal, but retrospective examination
      disclosed extracranial VA dissection in the V3 segment in both cases. Arterial
      dissection resulting in embolic stroke in the territory of the ipsilateral
      posterior inferior cerebellar artery was highly suspected. Both patients were
      treated conservatively without sequelae. Careful angiographic interpretation is
      important for the diagnosis of extracranial VA dissection. Spontaneous
      extracranial VA dissection should be suspected in young patients presenting with
      ischemic stroke but without predisposing risk factors or associated trauma.

PMID- 10892268
TI  - Frontal lobe infarction due to hemodynamic change after surgical
      revascularization in moyamoya disease--two case reports.
AB  - A 60-year-old female and a 40-year-old male underwent surgical revascularization
      for moyamoya disease and suffered small infarction in the ipsilateral frontal
      lobe 3 or 4 days postoperatively. Neuroimaging suggested that the bypass flow had
      caused rapid progression of occlusive changes in the carotid forks, a diminishing
      of moyamoya vessels, and flow reduction in the anterior cerebral artery
      ipsilateral to surgery, leading to critical ischemia in the frontal lobe.
      Surgical revascularization improves the outcome of patients with moyamoya
      disease, but postoperative management such as hydration is important to avoid
      ischemic complications due to frontal lobe infarction.

PMID- 10892269
TI  - Multiple arteriosclerotic fusiform aneurysms of the superficial temporal artery-
      case report.
AB  - Superficial temporal artery (STA) aneurysms are very rare, and usually occur in
      young adult men due to blunt trauma as pseudoaneurysms. An 85-year-old male
      presented with two non-traumatic STA aneurysms. The aneurysms were ligated and
      resected. Histological examination showed arteriosclerotic fusiform aneurysm. The
      pathogenesis of non-traumatic aneurysm of the STA appears to be arteriosclerotic
      change and/or hemodynamic stress.

PMID- 10892270
TI  - Repeated hemorrhage in ciliated craniopharyngioma--case report.
AB  - A 49-year-old female presented with a ciliated craniopharyngioma manifesting as
      repeated intratumoral hemorrhage. Histological examination suggested that the
      hemorrhage originated from the many thin blood vessels in the cyst wall stroma
      associated with inflammation. Symptomatic hemorrhage in cystic craniopharyngioma
      may mimic pituitary apoplexy but the etiology is quite different. Minor
      hemorrhage may recur unless the cyst wall is totally removed.

PMID- 10892271
TI  - Malignant melanoma arising from the sphenoidal sinus--case report.
AB  - Malignant melanomas arising from the sella turcica or sphenoidal sinus with
      bilateral invasion of the base of the skull or cavernous sinus are extremely
      rare. Whether the sella turcica or sphenoidal sinus is the site of origin is
      difficult to determine based on neuroradiological findings. An 83-year-old
      Japanese female presented with headache as the initial symptom. She suffered
      rapid progression of bilateral obstruction of the nasal cavity, left nasal
      bleeding, and bilateral visual field defects. The preoperative diagnosis was
      pituitary adenoma, metastatic tumor, or malignant paranasal tumor. Biopsy was
      performed. The histological diagnosis was malignant melanoma. Postoperatively,
      the tumor progressed rapidly. She suffered several cranial nerve pareses and
      hypopituitarism. She died within 6 months. Tumors arising from the sphenoidal
      sinus cause obstruction of the nasal cavity or nasal bleeding first, and then
      cause cranial nerve pareses by invasion of the cavernous sinus. This sequence of
      clinical manifestations can be attributed to the anatomical relationships between
      the sphenoidal sinus, nasal cavity, and cavernous sinus. Differential diagnosis
      of the origin in the sella turcica or sphenoidal sinus appears to be relatively
      easy based on further observation of the clinical course and symptoms.

PMID- 10892272
TI  - Ulnar neuropathy caused by a lipoma in Guyon's canal--case report.
AB  - A 74-year-old female presented with a 3-month history of compression neuropathy
      of the right ulnar nerve in Guyon's canal. Magnetic resonance imaging and
      ultrasonography revealed the location of the mass lesion. Surgical exploration
      discovered a lipoma pressing against both the ulnar nerve and the ulnar artery.
      The mass was extirpated. The postoperative course was uneventful with good
      function recovery.

PMID- 10892273
TI  - Symptomatic arachnoid cyst of the left frontal convexity presenting with memory
      disturbance--case report.
AB  - A 48-year-old female presented with vertiginous feeling and behavior disturbance.
      Computed tomography showed an arachnoid cyst on the left cerebral convexity.
      Single photon emission computed tomography revealed decreased cerebral blood flow
      (CBF) in the left frontal lobe. The Wechsler Memory Scale-Revised test
      demonstrated memory dysfunction. The arachnoid cyst was partially removed.
      Disturbances in CBF and behavior disappeared postoperatively. Local ischemia
      induced by compression due to arachnoid cyst may cause memory dysfunction and
      behavior disturbance. Neuropsychometric examination is useful for the evaluation
      of such symptoms.

PMID- 10892274
TI  - Shunt tube problems due to placement of valves on the chest wall--three case
      reports.
AB  - Programmable valves are often used for ventriculoperitoneal (VP) shunts with the
      shunt valve positioned on the chest wall. Three cases of shunt problems occurred
      due to placement of the valve on the chest wall. A 43-year-old male was treated
      with a VP shunt, and suffered shunt malfunction due to dislocation of the
      ventricular tube. A 21-year-old male was treated with a VP shunt, and suffered
      shunt malfunction due to disconnection of the shunt tube. A 4-day-old female
      neonate was treated with a VP shunt, and suffered migration of the shunt valve.
      The shunt system has two anchor sites on the head and chest wall, with the neck
      between the two anchor sites. High tension is sometimes caused in the shunt tube
      between the two points due to movement of the neck or growth, and may induce such
      dislocation and disconnection of the shunt tube. We recommend a longer shunt tube
      in such cases.

PMID- 10892275
TI  - [Pars plana vitrectomy in diabetic retinopathy. From pathogenetic principle to
      surgical strategy].
AB  - Diabetic retinopathy is the most important manifestation of diabetic eye disease.
      There are retinopathy, maculopathy, pathology of the vitreoretinal interface, and
      tractional retinal detachment. The development of surgical approaches based on
      pathogenetic ideas are shown. The beneficial effect of pars plana vitrectomy for
      persisting and recurrent vitreous hemorrhage, epiretinal fibrovascular
      proliferation, and retinal detachment is discussed. The surgical skills and
      experiences in diabetic eyes are stressed.

PMID- 10892276
TI  - [Intraocular pressure response after administration of 3 different viscoelastic
      agents after cataract operation].
AB  - By using three different viscoelastics [Adatocel (methylhydroxypropylcellulose),
      Amvisc Plus (sodium hyaluronate) and Healon (sodium hyaluronate)] a prospective
      randomized study was conducted to investigate whether postoperative intraocular
      pressure shows significant differences according to the viscoelastics used after
      150 cases of cataract surgery. PATIENTS AND METHODS: The inclusion criteria for
      this study were: extracapsular cataract extraction via the usual small-incision
      techniques and endocapsular posterior-chamber lens implantation. A total of 150
      eyes were operated upon. The patients were randomly assigned to three groups
      according to the viscoelastics, 50 cases used adatocel, 50 Amvisc Plus and 50
      Healon. As far as possible, the viscoelastics were sucked out under visual
      control. Intraocular pressure (IOP) was measured after 6 and 24 h. RESULTS: Six
      hours postoperatively, no statistically significant difference between the
      intraocular pressure after using different viscoelastics (adatocel: 19.6 +/- 9.7
      mmHg, Amvisc Plus: 20.5 +/- 9.6 mmHg und Healon: 21.8 +/- 8.8 mmHg) was seen. At
      24 h IOP was statistically significant higher for Healon than for adatocel and
      Amvisc Plus (adatocel: 16.3 +/- 4.8 mmHg, Amvisc Plus: 16.5 +/- 4.6 mmHg and
      Healon: 19.7 +/- 6.6 mmHg). CONCLUSIONS: Six hours postoperatively after
      phacoemulsification there was no significant difference between the IOP using
      different viscoelastics adatocel, Amvisc Plus and Healon. Twenty-four hours
      postoperatively a significantly higher intraocular pressure was measured for
      Healon than for the other viscoelastics.

PMID- 10892277
TI  - [Are filtering interventions in glaucoma patients with extensive visual field
      defects associated with a higher functional risk?].
AB  - BACKGROUND: We evaluated the prevalence of the loss of visual acuity due to loss
      of the central portion of the visual field and foveolar fixation in the first
      week after glaucoma filtering surgery. PATIENTS AND METHODS: We included 408
      patients, in whom glaucoma filtering surgery was performed between January 1993
      and April 1997 at the University Eye Clinic in Tubingen and who had completed 1
      year follow-up examinations. The retrospective evaluation included preoperative,
      intraoperative and postoperative data. We excluded all patients who did not
      complete 1-year follow-up examinations (12 +/- 3 months), who have died during
      the 1-year follow-up, who had combined glaucoma and cataract surgery or in whom
      the Molteno implant procedure was performed. RESULTS: A total of 404 patients
      (99.3%) did not suffer loss of the central visual field and foveolar fixation in
      the first week after glaucoma filtering surgery. In 11 cases, loss of visual
      acuity > 2 dB was due to progressive lens opacification. One patient suffered
      from postoperative progression of his age-related maculopathy. In one patient
      (0.2%) progression of a preexisting relative central scotoma occurred immediately
      after the operation. Two patients (0.5%) suffered from loss of fixation and the
      central visual field immediately after glaucoma filtering surgery. CONCLUSIONS:
      Loss of the central visual field and central fixation immediately after glaucoma
      filtering surgery is a rare complication. Therefore, glaucoma filtering surgery
      can also be recommended for patients with advanced visual field defects.

PMID- 10892278
TI  - [Intraocular metastases of metastatic breast carcinoma in the woman. Incidence,
      risk factors and therapy].
AB  - BACKGROUND: The breast cancer metastasis is the most common intraocular tumor in
      females. Aim of this study was to determine incidence and risk factors for
      intraocular metastasis and to evaluate the benefit of an early treatment.
      PATIENTS AND METHODS: 151 patients suffering from metastatic breast cancer were
      screened for the presence of intraocular metastasis. The medical history and the
      tumor status at the time of screening were evaluated and risk factors for
      intraocular metastasis were determined. In case of choroidal metastasis external
      beam radiotherapy was performed. RESULTS: Intraocular metastasis was found in 7
      out of 151 patients screened (4.6%). In one patient metastasis was located in the
      iris, in 6 patients in the choroid. Intraocular metastasis was only found in
      patients with more than one other organ system involved into disease (p = 0.002).
      In this subgroup of patients (n = 65) prevalence of intraocular metastasis was
      10.8%. Other risk factors for intraocular metastasis were presence of lung
      metastasis or brain metastasis. In 5 out 6 patients with choroidal metastasis
      external beam radiotherapy was performed, resulting in durable regression of
      metastasis and stabilization or improvement of visual acuity. CONCLUSION: The
      prevalence of intraocular metastasis in metastatic breast cancer was determined
      to be 4.6%. It is most commonly located in the choroid and develops in the course
      of advanced metastatic disease. Since early external beam radiotherapy of
      choroidal metastasis prevents functional loss, patients at risk should be given
      an ophthalmological screening for intraocular metastasis.

PMID- 10892279
TI  - [Blue-yellow perimetry in rhegmatogenous retinal detachment. Studies before and
      after therapy in comparison with white-white perimetry].
AB  - INTRODUCTION: Disturbance of the blue light perceptance in rhegmatogenous retinal
      detachment was demonstrated by Kollner 1907 with the help of colour-perimetries.
      We examined the blue- and white-function after retinal reattachment by blue-on
      yellow-perimetry compared with white-on-white-perimetry. PATIENTS AND METHODS: 10
      Patients with rhegmatogenous retinal detachment and a visual acuity > or = 0.1
      were examined preoperatively, 4 days and 6 weeks after successful buckling
      procedure. We performed a white-on-white-perimetry as also perimetries with blue
      stimuli on a yellow luminance background (program 30-2 of the Humphrey Field
      Analyzer 750). RESULTS: Four days after surgery the increase in sensitivity was
      significantly less for the blue-function compared with the white-function.
      Preoperatively and 6 weeks postoperatively the sensitivities were not
      significantly different. Between these time-points function recovered in average
      for both methods from MD -15 dB to MD -5 dB. CONCLUSION: After successful retinal
      detachment surgery the blue- and white-function increased. Blue-on-yellow
      perimetry showed more retinal sensitivity loss than white-on-white-perimetry
      immediately after surgery. Blue-on-yellow-perimetry measured the same retinal
      sensitivity loss as white-on-white-perimetry preoperatively and 6 weeks
      postoperatively.

PMID- 10892280
TI  - [Early and late findings with optical coherence tomography (OCT) in patients with
      postoperative hypotonia].
AB  - PURPOSE: To study early and late findings of macular retinal thickness in
      patients with hypotony following filtering procedures. PATIENTS AND METHODS: 13
      patients who had undergone trabeculectomy (9 with antimetabolites) developed
      ocular hypotony. The macular region appeared normal during biomicroscopy in 8
      patients. In the hypotensive phase, macular thickness was measured using optical
      coherence tomography (OCT). Directly after attempted and successful normalization
      of intraocular pressure (7 spontaneous, 5 operative, 1 failure) as well as 6
      months later, OCT measurements were repeated. Foveal thickness in the hypotonous
      eye was correlated with visual acuity and foveal thickness in the fellow eye.
      RESULTS: Intraocular pressure could be raised from a mean of 2.5 +/- 1.3 mmHg to
      11.5 +/- 5.5 mmHg and later on to 13 +/- 3.7 mmHg (follow-up). Mean foveal
      thickness was reduced from 211 +/- 73 microns during hypotony to 170 +/- 44
      microns after normalization of intraocular pressure and to 171 +/- 38 microns at
      late follow-up. Mean visual acuity improved from 0.17 to 0.33 and finally to 0.6.
      CONCLUSIONS: Despite normal appearance of the macula (8 patients) using
      biomicroscopy in patients with hypotony, retinal thickness in the fovea is
      increased. Apart from refractive changes, this retinal thickening can be held
      responsible for the deterioration of visual acuity in eyes with hypotony. OCT
      analysis and measurements may be useful to distinguish between retinal thickening
      that is reversible after normalization of intraocular pressure and cystoid
      macular edema that leads to permanent visual impairment.

PMID- 10892281
TI  - [Telomerase activity in uveal melanomas].
AB  - BACKGROUND: The maximum number of cell divisions of a certain cell population is
      genetically fixed so that aging cells become non-dividing (senescent) at least.
      This replicative life span, also known as "Hayflick limit", is probably defined
      by a "critical" length of the telomeres. Telomeres are special DNA-sequences
      located at the four ends of the chromosomes which are shortened with each cell
      cycle. Cells of most, but not all malignant tumours have been shown to reactivate
      the enzyme telomerase so that telomeres can be reconstructed, "Hayflick limit"
      can be overcome, and unlimited cell division can be established. This study was
      undertaken to elucidate whether telomerase reactivation is used by uveal melanoma
      cells. MATERIALS AND METHODS: Fresh tumour tissue was removed from 10 untreated
      uveal melanomas after enucleation. Telomerase activity was determined using a PCR
      ELISA according to the Telomeric Repeat Amplification Protocol (TRAP). Normal
      tissue of the skin and the conjunctiva served as control. RESULT: Telomerase
      activity was detectable in 90% of the investigated uveal melanomas. All control
      specimens were telomerase negative. CONCLUSIONS: Uveal melanoma growth seems to
      depend on telomerase reactivation. Thus, telomerase inhibition could offer a new
      principle for uveal melanoma therapy in the future.

PMID- 10892282
TI  - [Dislocation of artificial lenses into the vitreous body. Long-term follow-up of
      6 patients].
AB  - BACKGROUND: Dislocation of an artificial intraocular lens (IOL) into the vitreous
      is a rare complication in cataract surgery. The removal of the IOL from the
      vitreous can be associated with various difficulties. As vitreal surgery in
      Latvia has been developed only during the last two years, patients with IOL
      dislocation prior to that time were only observed. The aim this study was the
      long-term observation of this patients. PATIENTS AND METHODS: 6 patients with
      dislocated IOLs in the vitreous were observed over various periods of time: 1
      patient for 6 years, 2 patients for 3 years, 2 patients for 2 years and in 1
      patient for 1 year. A second IOL was implanted into the anterior chamber in two
      cases. RESULTS: In all cases the retina remained attached. Intraocular pressure
      was below 20 mmHg. Visual acuity was 0.4 (20/28) and 0.5 (20/40) in the two cases
      with secondary anterior chamber IOL. In the other cases visual rehabilitation was
      achieved with spectacles or contact lenses. Visual acuity was 0.7 (20/28) in one
      patient, 0.4 (20/50) in two patients and 0.1 (20/200) in one patient. CONCLUSION:
      Dislocated artificial intraocular lenses can remain in the vitreous for a long
      time without serious complications, if no vitreal surgery is possible.

PMID- 10892283
TI  - [Expansion of intraocular gas due to reduced atmospheric pressure. Case report
      and review of the literature].
AB  - Since the advent of vitrectomy and the increased use of intraocular gases, there
      had been concern voiced about the safety of air travel for patients with
      intraocular gas. Anecdotal reports and experimental models verify the danger of
      acute glaucoma and central retinal artery occlusion following depressurization
      and expansion of intraocular gas. However, the amount of gas, that can be
      compensated for, is a matter of controversy. CASE REPORT I: A 58-year old man
      underwent vitrectomy with intraocular air tamponade as a primary procedure for
      retinal detachment. The patient went home by airplane with a residual gas volume
      of less than 30% of the volume of the eye. Before takeoff at 530 m (1739 ft)
      above sea level, the intraocular pressure was 12 mmHg. During the ascent, severe
      ocular pain and loss of vision occurred. CASE REPORT II: A 38-year old woman
      underwent vitrectomy for primary repair of retinal detachment. The eye was
      injected with a 15% mixture of perfluoroethan (C2F6). When traveling home to
      Italy by car, the eye contained a residual gas volume of 50% of the volume of the
      globe. Intraocular pressure was 17 mmHg. During the ascent to the "Brennerpass",
      1375 m (4511 ft) above sea level, the eye became severely painful and vision was
      lost for approximately three minutes. Descending to a lower altitude relieved the
      symptoms. CONCLUSION: The expansion of intraocular gases depends on the
      atmospheric pressure and the mechanisms for compensation. Small volumes of
      intraocular gas or moderate traveling altitudes can cause a symptomatic rise in
      intraocular pressure.

PMID- 10892284
TI  - [Pigment epithelium hamartoma of the macula. 16-year-old patient with uncertain
      macula tumor].

PMID- 10892285
TI  - [Neuroretinitis].

PMID- 10892286
TI  - [Receptor diseases in the field of neurology].
AB  - Based on the gene-related function and molecular structure of various receptors,
      neurological receptor diseases were reviewed from both the immunologic and
      genetic perspectives. The nicotinic acetyl-choline receptor (AChR), ryanodine
      receptor (RyR), omega-conotoxin receptor (P/Q-type voltage-gated calcium
      channel), dihydropyridine receptor (L-type voltage gated calcium channel), and
      androgen receptor have been found to be affected by autoantibodies and/or genetic
      anomalies. They reflect on various neurological diseases such as myasthenia
      gravis, congenital myasthenic syndrome, malignant hyperthermia and central core
      disease, paraneoplastic myasthenic syndrome, hereditary migraine and ataxias,
      hypokalemic periodic paralysis, and bulbospinal muscular atrophy. The interaction
      of calcitonin gene-related peptide with its receptor tends to compensate the
      dysfunction caused by antibodies to AChR and RyR. One should look for cancers or
      genetic disorders in the case of the receptor disease implicated in calcium
      channel function. Recent advances in search for the etiology of these diseases
      from the standpoints of immunology and genetics have opened an avenue in
      understanding the functional structure of receptors and the molecular sites
      responsible for receptor diseases.

PMID- 10892287
TI  - [Molecular defects in hormone receptors and G proteins in human disorders].
AB  - The biological effects of hormones are mediated by plasma membrane and nuclear
      receptors which transmit extracellular signals to the cytoplasm and nucleus. The
      mutations in these receptors can affect normal signal transduction with loss-of
      function mutations leading to hormone resistance and gain-of-function mutations
      leading to constitutive activation of signaling pathways. Mutations in plasma
      membrane are involved in a large number of clinical disorders, including
      dwarfism, Laron syndrome, congenital hyperthyroidism or hypothyroidism,
      nephrogenic diabetes insipidus, resistance to TSH, LH, FSH and ACTH, Jansen's
      metaphyseal chondrodysplasia and autosomal dominant hypoparathyroidism. While,
      mutations in nuclear receptors are the cause of resistance to glucocorticoid,
      androgen, estrogen, thyroid hormone and vitamin D. The loss-of-function mutations
      leading to familial hormone resistance disorders are germ line in origin whereas
      the gain-of-function mutations leading to constitutively active receptors are
      somatic. The plasma membrane receptors for those disorders except GH resistance
      consist of seven spanning-transmembranes which couple with GTP binding (G)
      protein. Abnormal G protein also exhibits gain and loss of function for hormones,
      leading to tumors and pseudo-hypoparathyroidism, respectively. This review
      summarizes molecular defects in hormone receptors and G proteins and their
      associated clinical features.

PMID- 10892288
TI  - [The roles of cytokine receptors in diseases].
AB  - Cytokines are produced by various types of cells and have profound effects on the
      regulation of immune reactions, hematopoiesis, and inflammation. Herein, we will
      discuss the pathophysiological relevance of cytokine receptor expression,
      particularly focusing on chemokine receptor expression. Chemokines are cytokines
      with 4 cysteines at the well-conserved positions and exhibit potent chemotactic
      activities for various types of leukocytes. To date, accumulating evidence has
      indicated the potential involvement of these chemokines in inflammatory reactions
      through regulating inflammatory cell infiltration. Moreover, several lines of
      evidence demonstrate that different sets of chemokine receptors are expressed by
      T helper type 1 (Th1) and Th2 cells and that Th1 and Th2 cells respond to
      distinct sets of chemokines. These observations establish the essential roles of
      chemokines in helper T lymphocyte migration in vivo. Furthermore, several
      chemokine receptors are utilized as co-factors for human immunodeficiency virus
      entry and mutation in one chemokine receptor confers marked resistance to HIV
      infection. Therefore, the determination of chemokine receptors may provide
      invaluable information on the immune status and susceptibility to HIV infection.

PMID- 10892289
TI  - [Receptor and disease: genetic perspective].
AB  - Cells in higher animals communicate with each other using hundreds of kinds
      signaling molecules. Most of these signaling molecules are secreted from the
      signaling cell by exocytosis or diffusion. Regardless of the nature of the
      signal, the target cell responds by a specific protein called a receptor. It
      specifically binds the signaling molecule and then initiates a response in the
      target cell. Many genes for receptor molecules have been identified and mutations
      in many receptors are shown to be related to human diseases. In general, both
      genetic and environmental factors are involved in determining phenotypes
      including disease susceptibility. As the relative significance of genetic and
      environmental factors varies from disease to disease, we need animal models for
      human diseases to analyze these factors. It is now possible to manipulate mouse
      embryos to produce transgenic and knockout mice. These mice are quite useful for
      analyses of receptor functions and pathologic processes of disease development.
      As we only have about 6,000 mutant mice, we still need to produce at lease 94,000
      other kinds of mice. To achieve this goal, we have to carry out random
      mutagenesis, instead of homologous recombination in ES cells.

PMID- 10892290
TI  - [Analyses of amyloid formation mechanism in familial amyloidotic polyneuropathy
      and therapeutic trial].
AB  - Familial amyloidotic polyneuropathy (FAP) is characterized by systemic
      accumulation of amyloid fibrils in the peripheral nerves and other organs. FAP
      ATTR Val30Met is the most common of the familial forms of amyloidosis. In the
      Kumamoto district, 5 different points of mutation in transthyretin (TTR) have
      been discovered. To make a diagnosis of FAP, histochemical analysis using ATTR
      Val30Met monoclonal antibody and FAP patients' hair, and mass spectrometry which
      can analyze TTR post-translational modifications in the blood circulation and
      cerebrospinal fluid. From our examinations, oxidative stress and beta protein
      metabolism is deeply connected with amyloid formation mechanism. Liver
      transplantation for FAP is only the therapy to save the life of FAP patients. By
      1999, we had 17 FAP patients who underwent liver transplantation. They are all
      alive and showed some improvement predominantly in autonomic dysfunction after
      the surgery. Liver transplantation revealed that FAP does not progress if the TTR
      gene in the liver is normalized, suggesting the therapeutic possibility of gene
      therapy to the liver in FAP patients.

PMID- 10892291
TI  - [Diagnosis of neurodegenerative disease by mass spectrometry].
AB  - We analyzed wild-type and variant transthyretins (TTRs) by mass spectrometry and
      reported that all TTR preparations demonstrated free TTR, TTR conjugated with
      thiol compounds and several minor components. We previously described a component
      with a molecular mass 80 Da larger than free TTR, which was proven to be TTR
      conjugated with bisulfite. The amyloid fibril formation of purified TTR was
      monitored by the turbidity at 330 nm, and by a Congo red binding assay as a
      function of pH. The S-sulfonated TTR showed clear elevation of the turbidity and
      Congo red binding under acidic conditions. In contrast, TTR reduced by
      dithiothreitol, which was free of the S-sulfonated component, did not show
      evidence of amyloid fibril formation. We analyzed rabbit serum TTR obtained from
      a rabbit fed a diet containing sulfite and from a rabbit on a sulfite-free diet.
      Compared to that in the rabbit fed a sulfite-containing diet, sulfonated TTR was
      decreased on the 7th day of a sulfite-free diet. These results suggested that the
      S-sulfonated wild-type TTR is highly amyloidogenic, and that prolonged ingestion
      of antimicrobial and antioxidant agents containing sulfite/bisulfite, may cause
      senile systemic amyloidosis.

PMID- 10892292
TI  - [Physiopathology and molecular diagnosis for prion diseases].
AB  - Prion diseases, including Creutzfeldt-Jakob disease (CJD), are infectious
      neurodegenerative disorders. The etiological agent, prion, is postulated to
      consist mainly of a proteinase K-resistant isoform of prion protein (PrPSc) which
      is generated by post-translational conversion from the proteinase K-sensitive
      normal version (PrPC) physiologically expressed on the surface of neuronal and
      glial cells. The constitutive conversion results in the tremendous accumulation
      of PrPSc in the prion-infected brain. Homozygous disruption of the Prnp gene
      encoding PrPC renders mice resistant to prion, and the animals are no longer
      capable of generating PrPSc, indicating an essential role for PrPSc in the
      pathogenesis of prion diseases. The PrP-null mice (Ngsk Prnp0/0) revealed
      progressive ataxia due to the degeneration of cellebellar Purkinje cells at old
      ages. Successful rescue of Ngsk Prnp0/0 mice from neurodegeneration by a
      transgene encoding the normal mouse PrPC has indicated that the functional loss
      of PrPC is essential for this phenotype. Moreover, we detected aberrant mRNAs
      chimeric between Prnp exon 1-2 and a novel gene encoding PrP-like protein
      (PrPLP). These results suggested that, in addition to the functional loss of
      PrPC, ectopic expression of the PrPLP in the brain of Ngsk Prnp0/0 mice could be
      associated with Purkinje cell degeneration.

PMID- 10892293
TI  - [Expected usefulness of in situ hybridization for clinical pathology].
AB  - In situ hybridization technique was developed as molecular-histological
      usefulness at 1980's. To consider usefulness in the clinical pathology, we should
      recognize avairabilities of recent techniques such as DNA tip. The characteristic
      to in situ hybridization is summarized as follows. 1. Diagnosable gene expression
      pattern with histological feature in the section. 2. Need small amount of sample
      for hybridization. 3. Easy to distinguish expression of genes that show highly
      homologies. Previously, we developed non-radioisotopic in situ hybridization by
      digoxigenin-UTP labeled cRNA probe. The sensitivity and resolution are sufficient
      for detecting 50 copies mRNA in individual cells. This technique is expected to
      utilize for molecular diagnosis in clinical field in the near future.

PMID- 10892294
TI  - [Remodeling of basement membrane in association with cancer invasion].
AB  - Type IV collagen the major component of basement membrane (BM), is composed of
      six genetically distinct alpha chains. In normal breast tissue, benign breast
      tumors, and in the intraductal components of invasive ductal carcinoma, alpha 1
      (IV) and alpha 2 (IV) chains were stained in all BM, whereas alpha 5 (IV) and
      alpha 6 (IV) chains were restrictively localized in a linear pattern in the
      epithelial BM. However, in invasive ductal carcinoma, alpha 1 (IV) and alpha 2
      (IV) chains were discontinuously or negatively stained in the cancer cell nest,
      and the assembly of alpha 5 (IV) and alpha 6 (IV) chains into the BM was
      completely inhibited. The results indicate that the mammary gland forms a second
      network of BM composed of alpha 5 (IV)/alpha 6 (IV) chains, in addition to the
      classic network of alpha 1 (IV)/alpha 2 (IV) chains. Remodeling of type IV
      collagen alpha chains during the development of invasive breast cancer seems to
      be differentially regulated, and to be associated with modification of
      histopathological findings.

PMID- 10892295
TI  - [Telepathology at presence and in the future].
AB  - Telepathology is the performance of pathology at distance using available
      telecommunication links such as optic fiber, communication satellite, and
      integrated services digitized network (ISDN). The main applications of
      telepathology are to provide frozen section service, consultation between
      pathologists at a distance, and conducting conferences using displays. These
      activities are required due to the shortage and disproportional distribution of
      pathologists. Telepathology for frozen section service is fairly effective in
      providing indications for surgical procedures by discriminating malignant tumor
      from benign tumor, confirming metastasis to distant organs or lymph nodes, and
      decisions regarding the surgical margin. However, there are several public
      insurance problems in the spread and practice of telepathology. To solve these
      problems, not only from a medical approach but also from the development of
      mechanical engineering, economic and legal issues must be considered.

PMID- 10892296
TI  - [Diagnosis and management for antiphospholipid syndrome].
AB  - It has been reported that antiphospholipid antibodies have the diversity against
      epitopes and the clinical significance, while the concept of antiphospholipid
      syndrome has been established. Dr. Harris and Dr. Hughes proposed the diagnostic
      criteria for antiphospholipid syndrome, and their criteria were widely used.
      Thrombosis, recurrent fetal loss (intrauterine fetal death), thrombocytopenia,
      IgG anticardiolipin antibodies and lupus anticoagulants were adopted in their
      criteria. However, recent studies have revealed the evaluation of the
      standardization of the methods to detect antiphospholipid antibodies and the
      clinical significance of both anti-cardiolipin-beta 2-GPI complex antibodies and
      other isotypes of antiphospholipid antibodies. Thus, the preliminary
      classification criteria for antiphospholipid syndrome have been discussed. It has
      been reported that anticoagulation therapy is effective in the management of
      antiphospholipid syndrome by the recent retrospective studies. It is necessary to
      confirm these points by the prospective study in the near future.

PMID- 10892297
TI  - [The comparison of sensitivity between immunostaining and a simplified PCR-cold
      SSCP method in p53 genomic mutations].
AB  - The PCR-SSCP (single strand conformational polymorphism) method has been widely
      employed to screen mutations in a variety of genes because of its rapidity and
      simplicity in the operation. Using this method, we have examined mutations of
      some tumor-related genes including p53 and Ki-ras. In this study, we have
      evaluated the PCR-Cold (non radioactive) SSCP method for detection of p53 point
      mutations in comparison with immunohistological detection of p53 and PCR-direct
      sequencing. The results indicated that the PCR-Cold SSCP method had the same
      sensitivity with that of PCR-direct sequencing method, and had higher sensitivity
      than that of immunohistochemical method (IHC).

PMID- 10892298
TI  - [Homologous carcinosarcoma of the uterine corpus--report of a case and review of
      the literature in Japan].
AB  - A 59-year-old woman with leukorrhea. Aspiration smears were obtained from the
      uterine cavity. The dominant cellular components were fibrogenic sarcomatous
      cells, which had ill-defined lacy cytoplasm and a single nucleus with finely
      granular chromatin. There were occasional naked giant cells, and intracytoplasmic
      eosinophilic granules. Another infrequent cellular component was adenocarcinoma
      cells. Histopathologically, adenocarcinoma and spindle cell sarcoma were
      equivalently identified. Twenty-two cases of homologous carcinosarcoma of the
      uterine corpus were reviewed cytologically in Japan. Cytodiagnosis before
      treatment was positive for malignancy of carcinosarcoma in 28.6%. Characteristic
      cytological findings of this case were the presence of flat sheets of atypical
      cells with broad cytoplasm. These findings suggest epithelial features. However,
      the finely granular chromatin pattern and smooth nuclear membrane indicate
      sarcomatous cells.

PMID- 10892299
TI  - [Computer-supported poisonous plant information system for veterinary medicine].
AB  - Animals poisoned by plants are the subject of an increasing number of inquiries
      made to poison control centres. The most frequent questions are concerned with
      the identification of potentially toxic species and the choice of adequate
      therapeutic strategies. To meet this growing demand for information, we generated
      a database on poisonous plants to be used by veterinary practitioners. Relevant
      data were selected from the scientific literature and organised according to the
      requirements of a structured database. As a result, we now introduce a user
      friendly decision support system that is equipped with several search functions
      for fast and efficient retrieval of data. The information provided for each plant
      includes the degree of toxicity, major toxic constituents, their mechanism of
      action, pathological findings, clinical symptoms with brief case reports,
      therapeutic guidelines and references. In addition, each species is accompanied
      by a botanical description with photographic illustrations. This information tool
      on poisonous plants is available via the internet (http:www.vetpharm.unizh.ch) or
      compact disc, and can be accessed on Macintosh, Windows or UNIX using a browser
      that supports HTML 3.

PMID- 10892300
TI  - [Enzootic calcinosis in 16 cows from 6 dairy farms in Unterengadin].
AB  - Enzootic calcinosis was diagnosed in 16 cows, which originated from 6 dairy farms
      located in the Unterengadin valley in Switzerland between 1,402 and 1,650 metres
      above sea level. During the winter, the cows were fed haylage, which contained up
      to 50 per cent golden oat-grass (Trisetum flavescens), and hay and grain. The
      first symptoms of enzootic calcinosis were noted in March 1998, when some of the
      cows developed locomotor abnormalities. Additional cases were diagnosed during
      the following three months. The most important clinical findings were decreased
      milk production, weight loss, frequent recumbency, difficulty in rising, kneeling
      while rising and feeding, stilted gait, arched back, shifting weight from one
      foot to another and reluctance to remain standing after being roused. Of the 16
      cows, 5 had elevated concentrations of serum calcium and 10 had decreased
      concentrations of serum magnesium. All cows had normal or decreased
      concentrations of serum phosphorus, because the feeding of haylage containing
      golden oat-grass had been discontinued two months previously. In all of the cows,
      the most important postmortem findings were severe calcification of the aorta,
      iliac artery, brachiocephalic trunk and pulmonary artery.

PMID- 10892301
TI  - [Juvenile goiter in a goat herd in northwest Germany].
AB  - A continuous increase in the circumference of the thyroid gland was observed in
      four goat kids (44.4%) of the breed of White German Goat between the third and
      fourth month in a herd comprising White German Goats and Coloured German Goats.
      Clinical, laboratory diagnostic and chemically analytical results have been
      obtained, illustrated and compared with the equivalent parameters from healthy
      control herds without pathological findings. The thyroidal secretion rate and the
      milk iodine content were highly significant reduced in the affected flock in
      comparison with the control group. The feed which was given to the affected group
      did not cover the nutritional requirement of pregnant, lactating and growing
      goats. At 40-50 mg/l, the nitrate content of the water was close to the tolerance
      of 50 mg/l. It can be deduced from the findings available that the case described
      above is a synergetic combination of a primary iodine deficiency, based on an
      inefficient iodine supply and of a secondary iodine deficiency resulting from a
      super elevated nitrate content of the drinking water.

PMID- 10892302
TI  - Diabetic cataracts: different incidence between dogs and cats.
AB  - Diabetes mellitus is one of the most common endocrinopathies in the dog and cat.
      Diabetic cataract primarily affects the canine species and is rarely observed in
      the cat. It has been proposed that the incidence of cataracts in diabetic dogs is
      high because many of these patients have significant hyperglycemia despite
      insulin therapy. Age, gender, levels of serum glucose (before and during insulin
      therapy) and cataract formation were evaluated, retrospectively, in 23 dogs and
      22 cats with diabetes mellitus. In the canine population, the groups with the
      highest frequency of presentation were females and sexually intact animals. In
      contrast, males and neutered animals were the most prevalent groups in the feline
      diabetic population. Over 80% of diabetic cats and dogs were older than 7 years.
      Our results confirm the almost total lack of cataracts in diabetic cats, while
      they were present in more than half of the dogs. A relation between the incidence
      of cataracts and the correspondent level of hyperglycemia in the canine and
      feline species could not be established. The estimation of the relative risk for
      the development of cataracts in diabetic dogs shows that some population groups
      have a higher probability for suffering from this ocular alteration. A relation
      between relative risk and the correspondent level of hyperglycemia in the various
      groups was not found. This fact indicates that other factors are involved in the
      unequal appearance of diabetic cataracts in dogs and cats.

PMID- 10892303
TI  - [Psychopathology and treatment of traumatic mental disorders--on the vicissitude
      and controversy around theory and practice].
AB  - Recently, among advanced nations, including the United States, there have been
      growing interest in trauma related psychopathology. Regarding Japan, since
      Hanshin Awaji Great Earthquake and Sarin gas terrorism by Aum Shinrikyo, interest
      for psychological trauma has grown high. It is only about twenty years since
      active research and discussion around these issues started. Therefore, there are
      still hot dispute around psychopathology of these disorders. Also, therapeutic
      method is ever progressing. Regarding psychotherapy, there remain a lot of
      dispute and no general agreement has been made. In this paper, I would like to
      summarize the literature on psychological trauma and trauma-related
      psychopathology historically and provide current overview about the theory and
      practice of this pathology. The summary of the overview is as follows: 1.
      Psychological trauma is defined as a state caused by traumatic event described in
      DSM-IV, not as a traumatic event itself. Traumatic mental disorder should be
      understood as a spectrum of disorders, ranging from phobias and panic reactions
      related to distinct traumatic events to personality disorders, where intense and
      chronic traumatic experience is integrated into the personality organization. 2.
      Historically speaking, traumatic disorders were studied from two directions; war
      neuroses and etiology of hysteria. Each is corresponds to physioneurosis model
      and memory processing disturbance model, respectively, which is thought to be two
      major etiological models of this disorder. 3. Regarding treatment, although
      corresponding therapeutic idea for each model is provided, currently, most
      promising treatments are pharmacotherapy using SSRI and novel cognitive
      behavioral techniques such as PE (prolonged exposure treatment), SIT (stress
      inoculation training) and EMDR (eye movement desensitization and reprocessing).
      As for psychotherapy, hot arguments has been done as to how authentic recovered
      traumatic memories are and how to deal with them. Regardless of these disputes,
      it is essential to establish empathic therapeutic bond with the patients.

PMID- 10892304
TI  - [Social phobia with somatic symptoms including nausea and urgency of
      micturition].
AB  - The common symptoms of the social anxiety response include blushing, trembling,
      feelings of muscular tension of the face, and fear of eye contact. However, the
      ICD-10 mentions other less familiar symptoms such as nausea, urgency of
      micturition or defecation, gastrointestinal discomfort, and diarrhea as symptoms
      of social phobia. Since some of these somatic symptoms are classified as panic
      like symptoms in the DSM-IV, it is sometimes difficult to distinguish between
      social phobia and agoraphobia when these somatic symptoms appear in situations
      usually associated with agoraphobia. We investigated whether social phobic
      patients with familiar symptoms (classical group; N = 24) and those with
      unfamiliar symptoms such as nausea, urgency of micturition or defecation (N/U
      group; N = 13) could be distinguished on the basis of several selected
      demographic and psychological tests. Fear of negative evaluation (FNE), social
      avoidance and distress (SAD), brief social phobia scale (BSPS), and Rosenberg's
      self esteem score (Se) were compared among these two groups and 82 controls. We
      also investigated whether they have "fears of making other people feel
      uncomfortable" which is believed to be a characteristic symptom for what is known
      in Japanese as "taijin-kyofu-sho." Both groups had higher scores on FNE, SAD,
      fear and avoidance scores of BSPS, and lower scores on Se as compared with
      controls. However, neither group differed in demographic variables or results of
      psychological tests, except for higher scores on the performance score of BSPS
      and increased rate of "fears of making other people feel uncomfortable" in the
      classical group. It is suggested that social phobia patients had common social
      phobic symptomatology and psychopathology irrespective of their somatic symptoms.

PMID- 10892305
TI  - [Low-dose (0.5 mg) DST in manic and major depressive episodes: in relation to the
      severity of symptoms].
AB  - BACKGROUND: Results of previous studies and our own preliminary study suggest
      that the dexamethasone suppression test (DST) using 1 mg of dexamethasone might
      result in lower sensitivity in Japanese and Asian people with major depressive
      episodes, when compared to Caucasian people. We investigated the clinical utility
      of low-dose (0.5 mg) DST in Japanese patients with manic or major depressive
      episodes. METHODS: Low-dose (0.5 mg) DST was performed 276 times in 122 patients
      with bipolar disorder (manic or depressed) or major depressive disorder who
      visited the Department of Psychiatry of Osaka Prefectural General Hospital. After
      strict exclusion criteria were applied, the remaining 225 test results in 98
      patients were analyzed. The severity of symptoms was estimated in accordance with
      the DSM-IV, namely, severe, moderate, mild, or in remission. A 0.5 mg dose of
      dexamethasone was administered orally at 20:30, and blood samples were taken the
      following day at 8:00 (9:00 in outpatients) and 13:00. Serum cortisol levels were
      measured by radioimmunoassay. Nonsuppression was considered to have occurred when
      at least one of the postdexamethasone cortisol values was 4.0 micrograms/dl or
      over. RESULTS: In manic episodes, the postdexamethasone cortisol levels were
      significantly correlated with the severity of the symptoms, and the
      postdexamethasone cortisol levels in patients with severe symptoms were
      significantly higher than in those in remission. The rates of nonsuppression in
      manic episodes with severe, moderate, mild symptoms, and in remission, were 7/8
      (88%), 1/4 (25%), 1/3 (33%) and 2/7 (29%), respectively. In major depressive
      episodes, the postdexamethasone cortisol levels were significantly correlated
      with the severity of the symptoms. The rates of nonsuppression in major
      depressive episodes with each grading of severity were 47/58 (81%), 28/52 (54%),
      14/40 (35%), 10/53 (19%), respectively. In major depressive episodes, patients
      aged 50 or over showed significantly higher postdexamethasone cortisol levels
      than patients aged under 50. In particular, patients aged between 30 and 49
      showed significantly lower postdexamethasone cortisol levels than those in the
      other age groups. There was no significant difference between male and female
      patients (two-way ANOVA), but female patients with severe depressive symptoms
      showed significantly higher postdexamethasone cortisol levels than male patients
      with severe symptoms. There was no significant difference between bipolar and
      unipolar patients with major depressive episodes (two-way ANOVA), with the
      exception that the rate of nonsuppression in remission in bipolar patients was
      significantly different than that in unipolar patients (9/33 (27%), 1/20 (5%),
      respectively). Among major depressive disorders, the rate of nonsuppression was
      highest in those with psychotic features, followed by those with melancholia, and
      then by those without melancholia. Re-evaluating the cut-off point discriminating
      nonsuppression from suppression, it was suggested that the optimal cut-off point
      might differ according to age and gender, but a fixed cut-off point at 4.0
      micrograms/dl was considered to be appropriate. The postdexamethasone cortisol
      levels of samples obtained at 13:00 were more sensitive than those obtained at
      8:00 or 9:00. The exclusion criteria and the clinical meanings of DST were
      discussed. CONCLUSIONS: Along with the previous studies indicating a low rate of
      nonsuppression in Japanese and other Asians using a standard 1 mg DST, our
      results suggest that low-dose (0.5 mg) DST is better in Japanese, and probably in
      most Asian patients, than 1 mg DST.

PMID- 10892306
TI  - [Two siblings with adult-type metachromatic leukodystrophy: correlation between
      clinical symptoms and neuroimaging].
AB  - We reported two siblings with adult-type metachromatic leukodystrophy (MLD).
      Patient 1 was a 19-year-old male, and patient 2 was a 20-year-old female. Their
      initial symptoms were similar. They developed abnormal behavior and personality
      changes, poor concentration, and inappropriate smiling. In patient 1, his
      condition deteriorated and he developed incontinence. His attention span and
      verbal expression severely decreased. He had an inability to engage in meaningful
      conversation. The siblings were diagnosed as having MLD by marked reduced
      leukocyte arylsulfatase A activity. T2-weighted MRI of these two cases showed a
      high intensity area in the cerebral white matter. The high intensity areas of the
      cerebral white matter gradually spread over one year. However, SPECT of these
      cases showed only a few abnormal findings in the initial stage. Using SPECT, a
      reduction of regional cerebral blood flow (rCBF) spreading to the cerebral cortex
      was seen over one year after it was seen using MRI. The discrepancy between MRI
      and SPECT findings in the initial stage was characteristic. MLD is an important
      disease that involves white matter dementia. The discrepancy between MRI and
      SPECT is helpful to diagnose white matter dementia.

PMID- 10892307
TI  - WHO Expert Committee on Malaria.
AB  - Despite considerable progress in malaria control over the past decade, malaria
      remains a serious problem--particularly in Africa, south of the Sahara, where
      about 90% of clinical cases occur. Malaria, either alone or in combination with
      other diseases, is estimated to kill between 1.1 and 2.7 million people worldwide
      each year, and over 2400 million remain at risk. This report of a WHO Expert
      Committee reviews the progress made since 1992 in the implementation of the
      Global Malaria Control Strategy and analyses the effect of health sector reforms
      on malaria control programmes. The importance of more recent initiatives, such as
      the Roll Back Malaria project, is also discussed. The report focuses on disease
      management and on drug resistance of malaria parasites, one of the greatest
      challenges currently facing control programmes. Guidance is given on how to
      predict, prepare for, control and prevent malaria epidemics, which threaten large
      areas of the world. The use of chemoprophylaxis and selective vector control in
      the prevention of malaria is discussed. As accurate epidemiological information
      is essential for assessing public health needs and for monitoring malaria control
      programmes, a number of standardized case definitions and indicators have been
      developed. In order to make programme activities effective and responsive to
      changing epidemiological situations, the report emphasizes the need for
      operational research at a national level. Although existing tools have had an
      impact on malaria morbidity and mortality, it is clear that much remains to be
      done. The report concludes with a list of recommendations to ensure that the
      present achievements are sustained and that a greater impact is made on the
      disease, particularly in Africa.

PMID- 10892309
TI  - Health tips. Don't ignore shaking chills.

PMID- 10892308
TI  - Sinus infection. Often mistaken for a cold.

PMID- 10892310
TI  - Another reason to exercise--improved mental health.

PMID- 10892311
TI  - Dead rattlesnakes can bite?

PMID- 10892313
TI  - Postural hypotension. Faintness upon standing.

PMID- 10892312
TI  - Pancreatitis. Painful attacks should not be ignored.

PMID- 10892314
TI  - Nutrition as you age. Your needs change.

PMID- 10892315
TI  - I recently noticed some blood in my semen. Should I be worried?

PMID- 10892316
TI  - What are those small "strings" I sometimes see float across my eye?

PMID- 10892317
TI  - Menopause and beyond. Advances in medicine, understanding, shift focus from an
      ending to a beginning.

PMID- 10892318
TI  - Oops! Let's use the national attention on health care errors.

PMID- 10892319
TI  - Let's get down to business. Maintaining nursing's priorities in a changing
      economy.

PMID- 10892320
TI  - Problems with propoxyphene.

PMID- 10892321
TI  - Bad baby. A crisis for a newborn and a new nurse.

PMID- 10892322
TI  - 'It's not my job'. Unlicensed assistive personnel should help with tasks, not
      patient assessment.

PMID- 10892323
TI  - The effects of professional discipline on nurses.

PMID- 10892324
TI  - NSAIDs: a Faustian bargain.

PMID- 10892325
TI  - NSAIDs & antihypertensives: an unhappy union.

PMID- 10892326
TI  - Overhauling the organ donation system.

PMID- 10892327
TI  - Emergency. Digitalis toxicity.

PMID- 10892328
TI  - The elderly woman at risk.

PMID- 10892329
TI  - Resources.com.

PMID- 10892330
TI  - Why care about Medicare reimbursement?

PMID- 10892331
TI  - Patient vs. employment abandonment.

PMID- 10892332
TI  - A systems approach to health care errors.

PMID- 10892333
TI  - Draft legislation offers a mixed bag.

PMID- 10892334
TI  - Perils in the air. Avoiding occupational asthma triggers in the workplace.

PMID- 10892335
TI  - Introduction: aging research comes of age.

PMID- 10892336
TI  - Aging clock: the watchmaker's masterpiece.
AB  - The phenomenon of cellular senescence has been known for almost four decades.
      Yet, until very recently, the molecular mechanisms that lead to senescence have
      been poorly understood. However, substantial progress has been made in the last
      few years toward identifying the pathways executing senescence. This r view
      focuses on two major advances in this field, the telomere aging clock theory and
      the cell cycle regulatory mechanisms in senescent cells. These recent studies
      indicate that cellular senescence is a highly elaborate and active process, which
      presumably works as an anti-oncogenic mechanism.

PMID- 10892337
TI  - Molecular basis of Alzheimer's disease.
AB  - Despite an exponential production of data, Alzheimer's disease (AD) remains an
      enigma. Unresolved questions persist in the face of the heterogeneity of this
      neuropathology. Recent progress in understanding mechanisms for AD results from
      the study of amyloid precursor protein (APP) metabolism and the involvement of
      senile plaque-associated proteins. In addition to the amyloid cascade hypothesis,
      alternative schemes emerge, in which the amyloid peptide is not the primary
      effector of the disease. Perturbations of vesicular trafficking, the cytoskeletal
      network, and membrane cholesterol distribution could be central events.
      Furthermore, since the physiological role of APP, presenilins, and apolipoprotein
      E in the central nervous system are not completely understood, their involvement
      in AD etiology remains speculative. New actors have to be found to try to explain
      sporadic cases and non-elucidated familial cases.

PMID- 10892338
TI  - Helicases and aging.
AB  - Studying monogenic hereditary disorders that manifest age-related phenotypes in
      cells, tissues, and the total organism would be helpful for clarifying the
      mechanisms of aging. In this context, seven human disorders that manifest age
      related phenotypes have been found to be caused by aberrations of five proteins
      with seven helicase motifs conserved in most of the helicases. These disorders
      are xeroderma pigmentosum, Cockayne syndrome, trichothiodystrophy, Bloom
      syndrome, Werner syndrome, X-linked alpha-thalassemia/mental retardation
      syndrome, and Juberg-Marsidi syndrome. A decline of probably pleiotropic and
      fundamental function of helicases in these disorders is, therefore, implied to
      underlie not only the various age-related phenotypes of the disorders but also
      the pleiotropic and universal nature of ordinary aging. Consistent with this
      implication, studies of these seven disorders suggest that their various age
      related phenotypes are caused by aberrations in multiple processes, especially
      transcription. Furthermore, a few studies imply some association between
      aberration of the helicases and phenotypes in ordinary aging.

PMID- 10892339
TI  - Cellular and molecular mechanism of low-turnover osteopenia in the klotho
      deficient mouse.
AB  - The mouse homozygous for a disruption of the klotho locus (KL-/- or klotho mouse)
      exhibited multiple pathological conditions resembling human aging. We observed
      osteopenia in KL-/- mice with a low bone turnover, in which the decrease in bone
      formation exceeded the decrease in bone resorption and resulted in net bone loss.
      This pathophysiology resembles closely that of senile osteoporosis in humans.
      Osteoblastic cells from KL-/- mice proliferated normally in vitro; however, they
      showed much lower alkaline phosphatase activity and mineralized matrix formation
      than those from control mice. Cultured osteoclastic cells from KL-/- mice had
      normal resorbing activity and survival rate, but the differentiation of
      osteoclastic cells from their precursors was significantly disturbed: in the co
      culture of osteoblastic cells and osteoclast precursor cells, the formation of
      tartrate-resistant acid phosphatase-positive multinucleated osteoclastic cells
      was extremely poor only when osteoclast precursor cells originated from KL-/-
      mice independently of the origin of the osteoblastic cells. In addition, we found
      that osteoprotegerin a secreted factor which inhibits osteoclastogenesis, was up
      regulated in KL-/- mice. We conclude that a defect in klotho gene expression
      leads to the independent impairment of osteoblast and osteoclast differentiation,
      which can be a cause of low-turnover osteoporosis.

PMID- 10892340
TI  - Endothelial dysfunction in the klotho mouse and downregulation of klotho gene
      expression in various animal models of vascular and metabolic diseases.
AB  - The human aging process is associated with vascular endothelial dysfunction.
      However, humoral factors which might protect against endothelial dysfunction
      during aging have not yet been identified. We recently identified the klotho gene
      as a possible regulator of human aging. In the present study using the klotho
      deficient heterozygous mouse, we examined whether the Klotho protein is a humoral
      factor protecting against endothelial dysfunction. We further cloned rat klotho
      cDNA and investigated whether klotho mRNA expression in rat kidney is altered
      under pathological conditions such as hypertension, hyperlipidemia, renal
      failure, and inflammatory stress. The Klotho protein itself, or its metabolites,
      promotes endothelial NO production in aorta as well as arterioles, and klotho
      mRNA in kidney is downregulated under sustained circulatory stress.

PMID- 10892341
TI  - A possible new role for the anti-ageing peptide carnosine.
AB  - The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) is found in
      surprisingly large amounts in long-lived tissues and can delay ageing in cultured
      human fibroblasts. Carnosine has been regarded largely as an anti-oxidant and
      free radical scavenger. More recently, an anti-glycating potential has been
      discovered whereby carnosine can react with low-molecular-weight compounds that
      bear carbonyl groups (aldehydes and ketones). Carbonyl groups, arising mostly
      from the attack of reactive oxygen species and low-molecular-weight aldehydes and
      ketones, accumulate on proteins during ageing. Here we propose, with supporting
      evidence, that carnosine can react with protein carbonyl groups to produce
      protein-carbonyl-carnosine adducts ('carnosinylated' proteins). The various
      possible cellular fates of the carnosinylated proteins are discussed. These
      proposals may help explain anti-ageing actions of carnosine and its presence in
      non-mitotic cells of long-lived mammals.

PMID- 10892342
TI  - Structure and function of eukaryotic peptide transporters.
AB  - The cotransport of protons and peptides is now recognised as a major route by
      which dietary nitrogen is absorbed from the intestine, and filtered protein
      reabsorbed in the kidney. Recently, molecular biology has had a very substantial
      impact on the study of peptide transport, and here we review the molecular and
      functional information available within the framework of physiology. To this end
      we consider not only the mammalian peptide transporters and their tissue
      distribution and regulation but also those from other species (including
      Caenorhabditis elegans) which make up the proton-dependent oligopeptide transport
      superfamily. In addition, understanding the binding requirements for transported
      substrates may allow future design and targeted tissue delivery of peptide and
      peptidomimetic drugs. Finally, we aim to highlight some of the less well
      understood areas of peptide transport, in the hope that it will stimulate further
      research into this challenging yet exciting topic.

PMID- 10892343
TI  - Dual action of the active oxygen species during plant stress responses.
AB  - Adaptation to environmental changes is crucial for plant growth and survival.
      However, the molecular and biochemical mechanisms of adaptation are still poorly
      understood and the signaling pathways involved remain elusive. Active oxygen
      species (AOS) have been proposed as a central component of plant adaptation to
      both biotic and abiotic stresses. Under such conditions, AOS may play two very
      different roles: exacerbating damage or signaling the activation of defense
      responses. Such a dual function was first described in pathogenesis but has also
      recently been demonstrated during several abiotic stress responses. To allow for
      these different roles, cellular levels of AOS must be tightly controlled. The
      numerous AOS sources and a complex system of oxidant scavengers provide the
      flexibility necessary for these functions. This review discusses the dual action
      of AOS during plant stress responses.

PMID- 10892344
TI  - Recent insights on RNA folding mechanisms from catalytic RNA.
AB  - Methods for probing RNA structure in real time have revealed that initial folding
      steps are complete in less than a second. Refolding of large catalytic RNAs in
      vitro often results in long-lived intermediates that reach the native structure
      very slowly. These kinetically trapped intermediates arise from alternative
      secondary structures that form early in the folding process. In cells, proteins
      modulate the outcome of RNA folding reactions by stabilizing specific
      conformations or by accelerating refolding of misfolded intermediates. At the
      same time, competition between metastable conformations provides a means for
      regulating the biological activity of transcripts.

PMID- 10892345
TI  - Origins and evolutionary diversification of the nuclear receptor superfamily.
AB  - Nuclear receptors (NRs), which include those for steroid and thyroid hormones as
      well as retinoids, are encoded by a large gene superfamily that has evolved to
      regulate nearly every facet of metazoan life, from development to basic
      metabolism. This article reviews the conservation in structure and function of
      distinct receptors across different species and attempts to draw conclusions as
      to the evolution of this gene superfamily. Although sequences related to NRs can
      be found in plants and yeast, gene sequence analyses suggest that the NR
      ancestor(s) first appeared in the early metazoans and subsequently diversified
      into the six receptor sub-families, which were already recognisable at the time
      of the Arthropoda-Chordata split over 700 million years ago. At the time when a
      primitive NR emerged, the basic components of the transcription regulatory
      machinery, which are conserved from yeast to vertebrates, were already in place
      and the ancestral NR must have evolved with the ability to communicate with them.
      The first such NRs likely acted as monomers and in a ligand-independent fashion.
      As members of the NR superfamily acquired the ability to hetero- and
      homodimerise, and to bind and be regulated by ligands, the functional complexity
      of the NR superfamily increased. This exponentially increasing complexity
      subsequently provided a potential driving force for evolution of higher organisms
      by supplying a sophisticated regulatory gene network that could control complex
      physiological processes during development and in adult organisms.

PMID- 10892346
TI  - Novel insecticidal toxins from nematode-symbiotic bacteria.
AB  - The current strategy of using transgenic crops expressing insecticidal protein
      toxins is placing increasing emphasis on the discovery of novel toxins, beyond
      those already derived from the bacterium Bacillus thuringiensis. Here we review
      the cloning of four insecticidal toxin complex (tc) encoding genes from a
      different bacterium Photorhabdus luminescens and of similar gene sequences from
      Xenorhabdus nematophilus. Both these bacteria occupy the gut of entomopathogenic
      nematodes and are released into the insect upon invasion by the nematode. In the
      insect the bacteria presumably secrete these insecticidal toxins, as well as a
      range of other antimicrobials, to establish the insect cadaver as a monocultural
      breeding ground for both bacteria and nematodes. In this review, the protein
      biochemistry and structure of the tc encoding loci are discussed in relation to
      their observed toxicity and histopathology. These toxins may prove useful as
      alternatives to those derived from B. thuringiensis for deployment in insect
      resistant transgenic plants.

PMID- 10892347
TI  - Pycnogenol inhibits tumor necrosis factor-alpha-induced nuclear factor kappa B
      activation and adhesion molecule expression in human vascular endothelial cells.
AB  - The transcriptional regulatory protein nuclear factor kappa B (NF-kappa B)
      participates in the control of gene expression of many modulators of inflammatory
      and immune responses, including vascular cell adhesion molecule-1 (VCAM-1) and
      intercellular adhesion molecule-1 (ICAM-1). The heightened expression of these
      adhesion molecules has been reported to play a critical role in atherosclerosis,
      inflammation, ischemic vascular disorders, diabetes, and cancer metastasis. In
      the present study, we investigated the effect of pycnogenol, an antioxidant
      phytochemical, on the activation of NF-kappa B and the induction of VCAM-1 and
      ICAM-1 in tumor necrosis factor (TNF)-alpha-treated human umbilical vein
      endothelial cells (HUVECs). Gel-shift analysis of HUVEC demonstrated that
      pretreatment with pycnogenol exhibited a concentration-dependent suppression of
      TNF-alpha-induced activation of NF-kappa B. Induction of VCAM-1 and ICAM-1
      surface expression by TNF-alpha was dose-dependently reduced by pycnogenol. TNF
      alpha significantly increased the release of superoxide anion and hydrogen
      peroxide from HUVECs. Pycnogenol dose-dependently inhibited their release. The
      ability of pycnogenol to inhibit NF-kappa B activation and VCAM-1 and ICAM-1
      expression suggests that this phytochemical may play an important role in halting
      or preventing the atherogenic process.

PMID- 10892348
TI  - Chromosome aberrations, micronuclei, and activity of superoxide dismutases in
      human lymphocytes after irradiation in vitro.
AB  - The goal of this study was to provide data on the dose-dependent production of
      dicentrics and micronuclei in human lymphocytes irradiated with 22.6 MeV protons
      and to estimate the possible contribution of intracellular superoxide dismutases
      (SOD) to the relative biological effectiveness (RBE) of protons. For the dose
      response study, heparinized whole blood of a healthy volunteer was irradiated
      with protons and X-rays employing radiation doses of 0.5-4 Gy. Three biological
      endpoints were analyzed: chromosomal aberrations, micronuclei, and specific
      activity of cytosolic (CuZnSOD) and mitochondrial (MnSOD) superoxide dismutases
      in harvested human blood cells. Dicentric dose-response curves fit a linear
      quadratic form (alpha = 0.094 +/- 0.006, beta = 0.032 +/- 0.001) induced with X
      rays and (alpha = 0.119 +/- 0.057, beta = 0.029 +/- 0.014) for 22.6 MeV protons.
      Protons were more effective than X-rays in producing exchanges, particularly at
      0.5 and 1 Gy. In contrast to X-ray irradiated samples where a significant
      increase in the specific activity of MnSOD was recorded (up to a radiation dose
      of 1 Gy), irradiation with protons markedly reduced its activity. As a
      consequence of the reduced activity of MnSOD, the chromosomal dose-response curve
      became quadratic. The RBE for dicentrics varies with dose (from 2.2 to 1.01) and
      reduced activity of MnSOD is an important contributor to the RBE of protons.
      SODs, particularly MnSOD, play an important role in defending DNA from reactive
      oxygen species. A reduced activity of SOD, particularly MnSOD, is an important
      contributor to the RBE of protons.

PMID- 10892349
TI  - Three-dimensional model of human TIP30, a coactivator for HIV-1 Tat-activated
      transcription, and CC3, a protein associated with metastasis suppression.
AB  - Human TIP30 is a cofactor that specifically enhances human immunodeficiency virus
      1 (HIV-1) Tat-activated transcription. The sequence of TIP30 is identical to that
      of CC3, a protein associated with metastasis suppression. TIP30/CC3 is a member
      of the short-chain dehydrogenases/reductases (SDR) family. Of the several
      experimentally determined SDR structures, Escherichia coli uridine diphosphate
      (UDP) galactose-4 epimerase is most similar to TIP30/CC3. Because the direct
      sequence similarity between TIP30/CC3 and E. coli UDP galactose-4 epimerase is
      low, we used the transitive nature of homology and employed two Aquifex aeolicus
      proteins as intermediaries in the homology modeling process. Comparison of our
      structural model with that of known SDRs reveals that TIP30/CC3 contains several
      well-conserved features, including a beta alpha beta fold at the amino terminus,
      which we predict binds NADP(H). TIP30/CC3 contains characteristic motifs at the
      catalytic site of SDRs, including a serine, tyrosine, and lysine that are
      important in catalyzing hydride transfer between substrate and cofactor. We also
      predict that a unique 20-amino acid sequence found at the amino terminus is an
      alpha-helix. Because this region contains several positively and negatively
      charged amino acids, it may dock TIP30/CC3 to other proteins. Our structural
      model points to this alpha-helix and the SDR-like part of TIP30/CC3 for
      mutagenesis experiments to elucidate its role in HIV-1 Tat-activated
      transcription, metastasis suppression, and other cellular functions.

PMID- 10892350
TI  - Independent modulation of collagen fibrillogenesis by decorin and lumican.
AB  - The leucine-rich proteoglycans (also known as "small, leucine-rich
      proteoglycans," or SLRPs) lumican and decorin are thought to be involved in the
      regulation of collagen fibril assembly. Preparation of these proteoglycans in
      chemical amounts without exposure to denaturants has recently been achieved by
      infecting HT-1080 cells with vaccinia virus that contains an expression cassette
      for these molecules. Addition of lumican and decorin to a collagen
      fibrillogenesis assay based on turbidity demonstrated that lumican accelerated
      initial fibril formation while decorin retarded initial fibril formation. At the
      end of fibrillogenesis, both proteoglycans resulted in an overall reduced
      turbidity, suggesting that fibril diameter was lower. The presence of both
      proteoglycans had a synergistic effect, retarding fibril formation to a greater
      degree than either proteoglycan individually. Competitive binding studies showed
      that lumican did not compete for decorin-binding sites on collagen fibrils. Both
      proteoglycans increased the stability of fibrils to thermal denaturation to
      approximately the same degree. These studies show that lumican does not compete
      for decorin-binding sites on collagen, that decorin and lumican modulate collagen
      fibrillogenesis, and that, in the process, they also enhance collagen fibril
      stability.

PMID- 10892351
TI  - Heart failure: management of patients with left-ventricular systolic dysfunction.
AB  - More than 2 million Americans have heart failure, and about 400,000 new cases are
      diagnosed each year. Mortality is high, with 5-year mortality in the range of 50
      percent. Many of the almost 1 million hospitalizations each year for heart
      failure might be prevented by improved evaluation and care. This Quick Reference
      Guide for Clinicians summarizes major recommendations in Heart Failure:
      Evaluation and Care of Patients with Left-Ventricular Systolic Dysfunction.
      Clinical Practice Guideline No. 11. The document was prepared by RAND, a
      nonprofit research and policy organization, and a private-sector panel of experts
      and consumers. Guideline recommendations are intended for use by a broad range of
      health care practitioners. The guideline recommendations are based on a
      combination of evidence obtained through extensive literature reviews and on
      expert judgment where evidence was lacking. Specific recommendations are made in
      the following areas: Prevention of heart failure with asymptomatic left
      ventricular systolic dysfunction. Approaches to diagnosis and initial evaluation
      of suspected heart failure. Hospital admission and discharge criteria.
      Pharmacological management. Patient counseling and education. Exercise and
      rehabilitation. Evaluation for myocardial revascularization. Patient monitoring
      and followup evaluation.

PMID- 10892352
TI  - High-quality mammography: information for referring providers.
AB  - This Quick Reference Guide for Clinicians contains highlights from Quality
      Determinants of Mammography, Clinical Practice Guideline No. 13 of interest to
      health care providers who refer women for mammography. The Quality Determinants
      of Mammography Guideline Panel, a private-sector panel of health care
      professionals and consumers, developed the Guideline after comprehensively
      analyzing the research literature and current scientific knowledge concerning
      elements necessary for high-quality mammography. Specific recommendations are
      made in the following areas: Components of complete breast cancer screening.
      Responsibilities of women, mammography facilities, and referring providers as to
      screening and followup care. Communication of results. Limitations of
      mammography. Certification of mammography facilities.

PMID- 10892353
TI  - The human genome and medical care in the new century.

PMID- 10892354
TI  - Children's health insurance: the difference policy choices make.
AB  - This paper provides estimates of the cost and coverage impacts of the new State
      Children's Health Insurance Program (SCHIP). The estimates reflect the many
      choices the states are given by the legislation: whether to use traditional
      Medicaid or establish separate state-run programs; how far to extend eligibility
      up the income distribution; and how much to use premiums. We estimate the impacts
      of these choices on participation by the uninsured as well as by the insured-
      that is, the crowd-out effect--and on public expenditures. We also estimate the
      savings to families and firms that substitute SCHIP for private coverage. We
      conclude with estimates of the cost and coverage impacts of the actual initial
      choices that states have made.

PMID- 10892355
TI  - Medicaid expansions and the crowding out of private health insurance among
      children.
AB  - This paper re-examines the magnitude of crowd out among children. We use
      longitudinal data that allow us to identify and differentiate groups of children
      based on whether their eligibility for Medicaid was affected by the program's
      eligibility expansions. We investigate whether changes in insurance coverage of
      children affected by the expansions differed from changes in insurance coverage
      of children unaffected by the expansions. For example, we directly measure
      whether there was a greater decrease in private insurance coverage among children
      who became eligible for Medicaid than among children whose eligibility was
      unaffected. Our results suggest that there was relatively little crowd out among
      children. We estimate that 18.9% of the recent increase in Medicaid enrollment
      came from private insurance.

PMID- 10892356
TI  - The effects of Medicaid expansions and reimbursement increases on dentists'
      participation.
AB  - North Carolina Medicaid increased nominal Medicaid reimbursement to dentists 23%
      from 1988 to 1991 and doubled enrollment through eligibility expansions from 1985
      to 1991. Using Medicaid claims data and panel data techniques, this analysis
      investigates the effect of these policy changes on the probability that a dentist
      participated in Medicaid, and on the number of Medicaid children seen per
      provider per quarter. The results suggest that eligibility expansions and
      reimbursement rate increases were only marginally effective in increasing access
      to dental services for the Medicaid population.

PMID- 10892357
TI  - Adverse selection and price sensitivity when low-income people have subsidies to
      purchase health insurance in the private market.
AB  - Policymakers interested in subsidizing low-income people's purchase of private
      insurance face two major questions: will such subsidies lead to adverse
      selection, and how large do the subsidies have to be to induce large numbers of
      eligible people to purchase the insurance? This study examines New Jersey's short
      lived experience with a premium subsidy program, Health Access New Jersey (Access
      Program). The program was for people in families with incomes below 250% of the
      poverty level who were not eligible for health insurance provided by an employer,
      or Medicaid or Medicare, and who wished to purchase policies in the state's
      individual health insurance market, the Individual Health Coverage Program.
      Surveying a random sample of Access Program policyholders, we compared their
      demographic and socioeconomic characteristics, as well as their health status, to
      those of other New Jersey residents who had family incomes below 250% of the
      poverty level to determine whether there was any evidence of adverse selection
      among the people who enrolled in the Access Program. The people who enrolled were
      not in worse health than uninsured people with incomes below 250% of the poverty
      level, but they were quite price sensitive. Most enrollees had incomes within the
      low end of the income eligibility distribution, reflecting the structure of
      rapidly declining subsidies as income increased.

PMID- 10892358
TI  - Clinical and socioeconomic determinants of health care use among HIV-infected
      patients in the Department of Veterans Affairs.
AB  - This study estimates the impact of clinical and socioeconomic characteristics on
      health care use for HIV-infected patients. Data come from the Department of
      Veterans Affairs (VA) HIV Registry, which electronically extracts data from
      patients' automated medical records, and from patient interviews. Unlike prior
      studies, this analysis includes a staging system incorporating CD4 count and AIDS
      defining diagnoses. Results showed that clinical factors were the most important
      determinants of health care use; socioeconomic variables were seldom significant.
      These findings were expected, since the VA is an equal access system, providing
      care regardless of socioeconomic status.

PMID- 10892359
TI  - The marginal benefits of invasive treatments for acute myocardial infarction:
      does insurance coverage matter?
AB  - This paper applies instrumental variable (IV) techniques and estimates the
      average benefits of invasive surgical treatments for marginal acute myocardial
      infarction (AMI) patients by insurance coverage. The study uses data from the
      Agency for Healthcare Research and Quality's Healthcare Cost and Utilization
      Project (HCUP), State Inpatient Databases for the state of Washington, for years
      1988-1993. We observed differences in average benefits for marginal patients
      across insurance subpopulations that cannot be explained by differences in
      measured clinical circumstances. Our empirical results show that the insurance
      subpopulations with the greatest estimated marginal benefits are those with the
      lowest expected payment generosity to providers. Because of the relatively weak
      explanatory power of our instruments for three insurance subpopulations, and
      because many of the parameter estimates across the insurance subpopulations are
      not statistically different from each other, policy recommendations should be
      approached cautiously. However, our application of IV techniques to AMI patients
      demonstrates the usefulness of this approach to estimate treatment effects across
      patient populations (e.g., across types of insurance coverage) for medical
      conditions of interest to policymakers. These estimates may help determine
      whether treatments are overutilized or underutilized.

PMID- 10892360
TI  - Managed care, distance traveled, and hospital market definition.
AB  - Does managed care insurance require patients to travel farther to receive
      hospital care? This question has major implications for antitrust policy and
      access to care. In spite of a general presumption that the answer is "yes," the
      question cannot be settled by a priori reasoning. Managed care has two effects on
      distance: 1) the direct effect of steering managed care consumers to particular
      hospitals, and 2) the indirect effect of higher managed care market share
      changing the market environment for consumers in general. The net effect of
      managed care on distance traveled could go either way. This paper measures both
      direct and indirect effects in a unique application of a spatial interaction
      model. We use individual discharge data, including payer information, from
      hospitals in 14 California counties over the period 1984-1993. We find that the
      direct effect leads to longer distances, but the indirect effect leads to shorter
      distances. Neither effect is large. Surprisingly, the net effect is slightly
      negative.

PMID- 10892361
TI  - Spiral computerized tomography (dual helical mode) as a detector of aortic
      atheromas in patients with stroke and systemic emboli: additional benefit of the
      contrast-enhanced technique.
AB  - BACKGROUND: Protruding aortic atheromas are a potential source of stroke and
      systemic emboli. The single modality currently available for their detection has
      been transesophageal echocardiography. However, TEE does not allow full
      visualization of the upper part of the ascending aorta and proximal aortic arch.
      OBJECTIVES: To investigate whether double helical computerized tomography--both
      with and without contrast injection--may represent a useful technique for
      noninvasive detection of PAA in stroke patients. METHODS: Forty consecutive
      patients > or = 50 years of age who sustained a recent ischemic stroke and/or
      systemic emboli (within 15 days after the onset of the event) were enrolled in
      the study and underwent TEE and DHCT without contrast injection using thin slice
      acquisition (3.2 mm thickness and 1.5 mm reconstruction increment). In addition,
      the last eight consecutive patients, after obtaining an unenhanced scan,
      underwent a contrast-enhanced DHCT following peripheral intravenous injection of
      a small amount of contrast material (15 ml of diatrizoate). RESULTS: PAAs were
      demonstrated by TEE in 18 patients (45%); in 16 of them (89%) the atheromas were
      recognized by DHCT. Of the 22 patients without PAA on TEE, DHCT confirmed their
      absence in 18 (82%). DHCT yielded a sensitivity of 89%, a specificity of 82%, and
      an overall accuracy of 85%. The total number of protruding plaques detected by
      TEE was 43, of which 41 (95%) were correctly identified by DHCT. The mean
      thickness of the plaques was 5.6 +/- 2.4 mm on TEE, and 5.4 +/- 2.3 on DHCT (P =
      NS), with a good correlation between the modalities (r = 0.84). Contrast-enhanced
      DHCT scans demonstrated absolute equivalence to TEE in aortic areas defined as
      "clearly visualized by TEE." DHCT detected PAA between the distal ascending aorta
      and the proximal arch in seven patients; these atheromas were not included in the
      comparative analysis. In these "occult" areas, DHCT may be superior to TEE.
      CONCLUSIONS: DHCT without contrast injection using thin slice acquisition may
      become a useful modality for rapid noninvasive detection of PAA. Contrast
      enhanced DHCT scans significantly improve imaging quality and may be superior to
      TEE in the upper ascending aorta and the proximal arch (areas not well visualized
      by TEE).

PMID- 10892362
TI  - Helicobacter pylori: seroprevalence and colorectal cancer.
AB  - BACKGROUND: Previous studies have published controversial results regarding a
      connection between Helicobacter pylori infection and colorectal cancer. One
      possible mechanism is increased gastrin secretion in subjects infected with H.
      pylori, insofar as gastrin is known to be a trophic factor for the colonic
      mucosa. OBJECTIVES: To investigate a possible role of gastrin secretion in H.
      pylori infection associated with colorectal cancer, and determine whether H.
      pylori infection is a factor in this disease. METHODS: The serum gastrin levels
      and the presence of H. pylori IgG antibodies were measured in 51 colorectal
      cancer patients and 51 control subjects. The cancer patients were also tested for
      carcinoembryonic antigen and CA 19-9. RESULTS: H. pylori IgG antibodies were
      found in the serum of 41 (80.4%) of the cancer patients compared to 32 (62.7%) of
      the control subjects (P = 0.05). A significant correlation was found between CA
      19-9 (r = 0.3432, n = 49, P = 0.01) and seropositive H. pylori IgG antibodies in
      the serum of the cancer patients (odds ratio 2.43, and 95% confidence limit 0.99
      5.95), but none between CEA and H. pylori IgG antibodies nor between the serum
      gastrin level and the presence of colorectal cancer. CONCLUSIONS: The results of
      this study indicate a significant association between seropositive H. pylori IgG
      antibodies and elevated CA 19-9 in colorectal cancer patients, but no correlation
      between the serum gastrin level and the presence of this cancer. H. pylori
      seropositivity is more prevalent in patients with colorectal cancer.

PMID- 10892363
TI  - Maternal obesity and pregnancy outcome.
AB  - BACKGROUND: Obesity, a common condition in developed countries, is recognized as
      a threat to health. OBJECTIVES: To describe the distribution of weight in
      pregnant women and evaluate the influence of obesity on pregnancy outcome in a
      high parity northern Israeli population. METHODS: The study included 887 women
      who gave birth in the Western Galilee Medical Center during the period August to
      November 1995. The patients were classified as underweight, normal weight,
      overweight, or obese according to body mass index. Maternal demographic,
      obstetric, and perinatal variables were compared. A control group of 167 normal
      weight women were matched with the obese group for maternal age, parity, and
      gestational age. RESULTS: Obese mothers had a higher incidence of gestational
      diabetes and pregnancy-induced hypertension compared to normal weight mothers
      (5.4% vs. 1.8%, and 7.2% vs. 0.6% respectively, P < 0.01), a higher rate of labor
      induction (20.4% vs. 10.2%, P < 0.01), and a higher cesarean section rate (19.6%
      vs. 10.8%, P < 0.05). There was also a significant difference in the prevalence
      of macrosomia in the offspring (16.8% vs. 8.4%, P < 0.05). CONCLUSION: Obese
      pregnant women are at high risk for complications during delivery and therefore
      need careful pre-conception and prenatal counseling, as well as perinatal
      management.

PMID- 10892364
TI  - Pterygium-induced corneal astigmatism.
AB  - BACKGROUND: Previous work has suggested an association between increasing size of
      pterygium and increasing degrees of induced corneal astigmatism. OBJECTIVES: To
      assess the quantitative relation between pterygium size and induced corneal
      astigmatism using a computerized corneal analysis system (TMS II) and slit-lamp
      beam evaluation of pterygium size, and to conclude whether corneal astigmatism is
      an early indication for surgical intervention. METHODS: We evaluated 94 eyes of
      94 patients with unilateral primary pterygium of different sizes, using TMS II
      and slit-lamp beam measurements of the size of the pterygium (in millimeters)
      from the limbus to assess parameters of pterygium size with induced corneal
      astigmatism. Best corrected visual Snellen acuity was performed. RESULTS: Primary
      pterygium induced with-the-rule astigmatism. Pterygium extending > 16% of the
      corneal radius or 1.1 mm or less from the limbus produced increasing degrees of
      induced astigmatism of more than 1.0 diopter. Significant astigmatism was found
      in 16.16% of 24 eyes with pterygium of 0.2 up to 1.0 mm in size, in 45.45% of 22
      eyes with pterygium of 1.1 up to 3.0 mm in size (P < or = 0.0004), and in 100% of
      3 eyes with pterygium of 5.1 up to 6.7 mm in size (P = 0.0005). We found that
      visual acuity was decreased when topographic astigmatism was increased.
      CONCLUSIONS: When primary pterygium reaches more than 1.0 mm in size from the
      limbus it induces with-the-rule significant astigmatism (> or = 1.0 diopter).
      This significant astigmatism tends to increase with the increasing size of the
      lesion. Topographic astigmatism tends to be improved by successful removal of the
      pterygium. These findings suggest that early surgical intervention in the
      pterygium may be indicated when the lesion is more than 1.0 mm in size from the
      limbus.

PMID- 10892365
TI  - Seasonal variation in sudden death in the Negev desert region of Israel.
AB  - BACKGROUND: Previous studies have documented an increased incidence of cardiac
      mortality and sudden death during winter months. OBJECTIVES: To evaluate seasonal
      variation in sudden death in a hot climate such as the desert region of southern
      Israel. METHODS: We analyzed the files of 243 consecutive patients treated for
      out-of-hospital sudden death by the Beer Sheva Mobile Intensive Care Unit during
      1989-90. Daily, monthly and seasonal incidence of sudden death was correlated
      with meteorological data, including temperature, heat stress, relative humidity
      and barometric pressure. RESULTS: The seasonal distribution of sudden death was
      23% in spring, 21% in summer, 25% in autumn and 31% in winter (not significant).
      In patients with known heart disease there were more episodes of sudden death in
      cold weather (< 15.4 degrees C) than hot (> 34.2 degrees C) (16 vs. 3, P < 0.05).
      Resuscitation was less successful in cold compared with hot weather (28 vs. 11, P
      < 0.05). Of patients older than 65 years, 11 sustained sudden death when heat
      stress was below 12.4 degrees C compared to 2 patients when heat stress was above
      27.5 degrees C (P = 0.05). CONCLUSION: Despite the warm desert climate, there
      were more cases of sudden death in older patients and in those with known heart
      disease during the winter season and on particularly cold days.

PMID- 10892366
TI  - Paroxysmal nocturnal hemoglobinuria associated with in vitro inhibition of
      erythropoiesis by bone marrow T lymphocytes.
AB  - BACKGROUND: The etiology of bone marrow failure, a prominent feature of
      paroxysmal nocturnal hemoglobulinuria, is presently unknown. OBJECTIVES: To
      evaluate the possible influence of cellular immune mechanisms in the bone marrow
      failure of PNH. METHODS: We studied marrow erythroid colony formation in a
      patient with paroxysmal nocturnal hemoglobinuria without hypoplastic/aplastic
      marrow complications. RESULTS: In vitro assays revealed a pronounced inhibition
      of primitive erythroid (BFU-E) progenitor cell growth by marrow T lymphocytes.
      Removal of T cells prior to culture resulted in a 4.5-fold enhancement of BFU-E
      numbers. Reevaluation of in vitro erythropoiesis during steroid administration
      indicated a persistent, albeit less prominent, T cell inhibitory effect.
      CONCLUSION: Our findings provide the first direct evidence for a cellular immune
      inhibitory phenomenon accompanying PNH.

PMID- 10892367
TI  - Incidence and mortality of Down syndrome.
AB  - Life expectancy for persons with Down syndrome has increased dramatically
      throughout the world over the last 50 years. In 1978 the Israel Ministry of
      Health initiated a national program for the prevention of birth defects, and
      since 1979 data on the incidence and mortality of persons with Down syndrome have
      been collected and analyzed. Data from this register are presented for the period
      1979-97 and compared to a previous study from Jerusalem for the period 1964-70.
      The actual incidence rate in 1997 was 1.1 per 1,000, but the total or true
      incidence rate (both live births and terminated pregnancies) was 2.32, which was
      not much different from the 1964-70 rate of 2.43. With regard to mortality, in
      1979 45.9% of the children born with Down syndrome died before the end of the
      first year; in 1996 only 8.6% died. In 1979 57.8% died before the age of 14,
      compared to only 10.5% in 1996.

PMID- 10892368
TI  - Gene therapy for peripheral vascular disease.

PMID- 10892369
TI  - Gene and immune-based therapies for genitourinary malignancies: current status
      and future prospects.

PMID- 10892370
TI  - Fetal intrauterine life--a window to adult disease?

PMID- 10892371
TI  - The role of the liver environment in the regulation of colon cancer metastasis.

PMID- 10892372
TI  - CMV colitis mimicking pseudomembranous enterocolitis.

PMID- 10892373
TI  - Congenital arteriovenous fistula with a massive aneurysm of the vein of Galen.

PMID- 10892374
TI  - Protruding aortic atheroma: is there a need for a new imaging modality?

PMID- 10892375
TI  - Out-of-hospital death in Israel--should we blame the weather?

PMID- 10892376
TI  - Gene therapy: the ball takes a spin towards multifactorial diseases.

PMID- 10892377
TI  - Primary rectal malignant melanoma.

PMID- 10892378
TI  - Huge subcapsular splenic hematoma in a patient with Gaucher disease.

PMID- 10892379
TI  - The Israel Heart Society Expert Consensus Document: the cardiac patient and
      sexual activity in the era of sildenafil (Viagra).

PMID- 10892380
TI  - David Ben-Gurion, Moshe Feldenkrais and Raymond Arthur Dart.

PMID- 10892381
TI  - Benjamin, another Talmudic physician.

PMID- 10892382
TI  - The matter of a name.

PMID- 10892383
TI  - Melanoma on kibbutzim.

PMID- 10892384
TI  - Melanoma on kibbutzim.

PMID- 10892385
TI  - Determinants of hospital utilization: the content of medical inpatient care in
      Israel.
AB  - BACKGROUND: The increasing utilization of general internal medicine hospital
      wards in Israel during the last decade is a source of concern for health policy
      makers. OBJECTIVES: To report on the distribution of selected main and secondary
      diagnoses among GIM inpatients, and to estimate the proportion of disorders for
      which appropriate care in the community will reduce the need for hospital
      admissions and re-admissions. METHODS: Data from the Health Information and
      Computer Services of the Israel Ministry of Health (national hospitalization
      database) for a one year period were analyzed by distribution of diagnostic
      entities (ICD-9-CM) in GIM and in medical subspecialty wards. RESULTS: Of the
      313,824 discharges from hospital divisions of medicine in 1995, 256,956 (81.9%)
      were from GIM and 56,868 (18.1%) from specialty wards. Main and secondary
      discharge diagnoses were available for 188,807 GIM and 35,992 specialty patients.
      Of all main diagnoses in GIM wards, 27% were coded as "general or systemic
      symptoms and signs" or as "abnormal laboratory or ill defined manifestations"
      (ICD-9-CM codes 780-799, 276,277), and heart diseases comprised another 27%. The
      remaining main diagnoses covered almost all medical conditions. The combined
      proportion of "ambulatory care sensitive hospital admissions" (bronchial asthma,
      hypertension, congestive heart failure, chronic obstructive pulmonary disease,
      diabetes) constituted 12% of all main diagnoses in GIM, and respiratory symptoms
      or signs comprised another 11%. A by-product of this analysis was an insight into
      the experience of undergraduate medical students in GIM. CONCLUSIONS: Assuming
      that 12-75% of admissions for "ambulatory care sensitive disorders" are
      preventable, an improved review before hospital discharge and a closer outpatient
      follow-up may reduce the load on GIM wards by 1-17%. This wide range justifies
      controlled trials to determine the effect of improved community care on hospital
      utilization. GIM wards offer valuable learning opportunities, but they cannot be
      a substitute for primary care clinics. The unexplained high proportion of GIM
      inpatients who were discharged with an unspecified main diagnosis could be
      detrimental for the accuracy of hospitalization statistics, and justifies
      investigation by chart audits into physicians' habits of documentation.

PMID- 10892386
TI  - Age-related seroprevalence of Cryptosporidium in northern Israel.
AB  - BACKGROUND: Two recent studies found that the prevalence of cryptosporidiosis
      among children in Israel was 3.4-7.4%. OBJECTIVES: To assess the cumulative
      infection rate by testing immunoglobulin A and G seroprevalence for
      Cryptosporidium in children and adults in Israel. PATIENTS AND METHODS: The
      seroprevalence of IgA and IgG anti-Cryptosporidium antibodies was determined by
      an enzyme-linked immunosorbent assay procedure in a group of 163 healthy children
      and adults. RESULTS: The overall seroprevalence rates for IgG, IgA, both IgA and
      IgG, and any immunoglobulin were 12.6%, 23%, 30% and 65.6% respectively. Half the
      children under the age of 12 years were already infected, with seroprevalence
      increasing to 95.6% in those over age 13 (P < 0.05). Seropositivity for IgG or
      IgA did not significantly increase with age. CONCLUSIONS: These results indicate
      that a large percentage of healthy children and adults in northern Israel have
      been infected with Cryptosporidium, and at early ages.

PMID- 10892387
TI  - Prenatal diagnosis for detecting congenital malformations: acceptance among
      Israeli Arab women.
AB  - BACKGROUND: A high rate of consanguineous marriages exists within the Israeli
      Arab community, with approximately half occurring between first cousins. This
      contributes towards a high incidence of congenital malformations and autosomal
      recessive diseases, many of which are detectable at prenatal diagnosis.
      OBJECTIVES: To assess the levels of both awareness and acceptance regarding
      prenatal diagnosis and termination of pregnancy among a group of Arab women in
      order to devise the optimal means of providing genetic counseling and general
      health services. METHODS: A total of 231 Arab women of childbearing age were
      interviewed 3 days postpartum to assess their knowledge of prenatal diagnosis and
      termination of pregnancy, their willingness to undergo prenatal diagnosis, and
      their opinions on termination of pregnancy in the event of a severely affected
      fetus. RESULTS: Half the women believed that prenatal testing is not an effective
      (or accurate) tool for diagnosing an affected fetus. A quarter had poor knowledge
      on prenatal diagnosis, and a quarter believed that prenatal diagnosis does
      provide the correct diagnosis. Ninety-five percent said they would agree to
      undergo prenatal diagnosis; and in the event of a severely affected fetus, 36%
      said they would agree to a termination of pregnancy, 57% said they would not, and
      7% were undecided. CONCLUSIONS: There is a need for special intervention
      programs, with guidance by health professionals, geneticists and religious
      authorities, that will inform this population on the increased risk associated
      with consanguinity, stress the importance and effectiveness of prenatal testing
      to identify severe congenital malformations, and help them to accept prenatal
      diagnosis and termination of pregnancy if indicated.

PMID- 10892388
TI  - Patients' smoking status: the family practice physician's view.
AB  - BACKGROUND: Smoking rates have decreased in western countries as well as in
      Israel during the past 20 years. OBJECTIVES: To estimate current rates of smoking
      and smoking cessation, and to assess factors associated with smoking and smoking
      cessation in family practice. METHODS: Prospective face-to-face interviews were
      conducted with 1,094 subjects, aged 16 years or older, registered in a family
      practice. RESULTS: Of all subjects studied, 746 (68.2%) were nonsmokers, 237
      (21.7%) were current smokers, and 111 (10.1%) had stopped smoking. Overall, 31.8%
      of the males and 13.8% of the females were current smokers, and 20.1% males and
      2.4% females had stopped smoking. Current smoking and smoking cessation rates
      were significantly and inversely associated with age among males and females.
      Smoking rates were higher among males and females who were married, had 10-12
      years of education, and among males of North African origin and females of
      Israeli origin. The number of cigarettes smoked per day was associated with
      smoking and smoking cessation in males, but not in females. The highest rate of
      quitting occurred among males who smoked > or = 25 cigarettes per day. In a
      multiple regression analysis, gender and the number of cigarettes smoked per day
      were the most significant factors that predicted smoking cessation. The most
      common reason for stopping was the appearance of new signs of illness or the
      development of a new chronic disease, followed by a physician's recommendation to
      quit smoking. CONCLUSIONS: Female smokers and male smokers who smoke less than 25
      cigarettes per day are the least likely to quit smoking. Future programs should
      be designed for and targeted at these groups of patients.

PMID- 10892389
TI  - Smoking cessation support groups in Israel: a long-term follow-up.
AB  - BACKGROUND: Smoking is the most important preventable cause of chronic disease in
      the western world. Many smokers want to quit, but have difficulty overcoming the
      addictive effect of nicotine. OBJECTIVES: To assess the quitting rate of smokers
      who participated in smoking cessation groups and to characterize predictors of
      success or failure over a 1-3 years follow-up period. METHODS: We studied 89
      participants in 7 groups. Questionnaires were completed at baseline and after a
      follow-up period of 1 to 3 years. Smoking cessation was determined by self-report
      and a carbon monoxide breath test. RESULTS: Of the 89 participants in the support
      groups 76 (85%) were located. An intention-to-treat analysis was done for these
      participants. At follow-up 25 (33%) were non-smokers. There was a 95% agreement
      rate between self-report of smoking status and CO breath analysis. There were no
      differences between quitters and non-quitters in education level, gender, age at
      initiation of smoking, previous quit attempts, extent of participation in group
      meetings, concern about gaining weight, Fagerstrom index, or the number of close
      friends or relatives who smoke. Belief in one's ability to quit, satisfaction
      with group meetings, and spouse support were significantly associated with
      success (P < 0.01). CONCLUSIONS: The quit rate was 33%. Self-report is a reliable
      method for assessing smoking status. Smokers' belief in their ability to quit
      must be reinforced. Spouse participation in some group meetings may be
      beneficial, as may the involvement of a dietician and an expert on exercise.
      Follow-up "booster" meetings may also help.

PMID- 10892390
TI  - Management of osteoporosis: a survey of Israeli physicians' knowledge and
      attitudes.
AB  - BACKGROUND: Osteoporosis is the most common human bone disease. It affects
      millions of persons throughout the world and its prevalence will increase as the
      population ages worldwide. OBJECTIVE: To assess Israeli physicians' attitudes and
      knowledge with regard to management of osteoporosis. METHODS: A questionnaire was
      mailed to 1,900 Israeli physicians concerning their attitudes to the management
      of osteoporosis, their prescribing habits, and their knowledge on the
      pharmacological treatment of the disease. RESULTS: Replies were received from 19%
      of the physicians. The respondents encouraged physical activity and cessation of
      smoking for all women, and prescribed estrogen replacement as the main treatment
      for 50-year-old women. A relatively low level of knowledge was found regarding
      the adequate dosage of several of the pharmacological treatments. CONCLUSIONS:
      The findings of the present study stress the need to provide clear guidelines and
      to extend physicians' knowledge regarding the management of osteoporosis.

PMID- 10892391
TI  - Cytokine response during hyperoxia: sequential production of pulmonary tumor
      necrosis factor and interleukin-6 in neonatal rats.
AB  - BACKGROUND: Exposure of newborn animals to high concentrations of oxygen leads to
      diffuse alveolar damage similar to that seen in bronchopulmonary dysplasia in
      human infants. Therefore, neonatal rats are a suitable practical model of
      hyperoxic lung damage in human infants. OBJECTIVE: To determine the involvement
      of tumor necrosis factor-alpha and interleukin-6 in lung injury in neonatal rats
      exposed to 100% O2 concentration. METHODS: A randomized controlled study was
      designed in which litters of term Sprague-Dawley rat pups were assigned to
      experimental or control groups. The pups in the experimental group were placed in
      100% O2 from birth for 9 days, while the control pups were placed in room air.
      Twelve to 15 pups from each group were sacrificed on day 1, 3, 6, 9 and 13 after
      birth for bronchoalveolar lavage collection and lung histologic study. The
      bronchoalveolar lavage fluid was assayed for TNF alpha and IL-6. RESULTS: Newborn
      rats exposed to 100% O2 for the first 9 days of life showed severe pulmonary
      edema and hypercellularity on days 1 and 3, which then improved to nearly
      complete resolution on days 6 and 9. Pulmonary TNF alpha was produced early on O2
      exposure (day 3) and pulmonary IL-6 later (days 6 and 9). CONCLUSIONS: Hyperoxia
      induces sequential production of pulmonary TNF alpha and IL-6, which corresponds
      to the severity of the pathological findings and the known inflammatory and anti
      inflammatory role of these cytokines.

PMID- 10892392
TI  - Understanding hospital utilization: medical inpatient care in Israel.

PMID- 10892393
TI  - Smoking--the next-door killer.

PMID- 10892394
TI  - Consensus conference as a tool for national health services policy: the case for
      osteoporosis.

PMID- 10892395
TI  - Minimally invasive surgery in childhood: current status.

PMID- 10892396
TI  - The new prognosis of systemic lupus erythematosus: treatment-free remission and
      decreased mortality and morbidity.

PMID- 10892397
TI  - High dose intravenous immunoglobulins: a new step in the treatment of systemic
      lupus erythematosus.

PMID- 10892398
TI  - Myocardial preconditioning in humans.
AB  - The exact role of myocardial preconditioning in patients with coronary artery
      disease is not clear. Preconditioning rapidly develops during coronary
      angioplasty. Myocardial preconditioning probably plays a role in reducing the
      myocardial infarct size in patients with preceding angina by direct effect,
      rendering the myocytes more resistant to ischemic injury, by acceleration of
      thrombolysis, and probably by the increasing recruitment of collaterals. It is
      also possible that the higher mortality among diabetic patients on sulfonylureas,
      and their worse outcome during acute myocardial infarction, are related to
      blockade of preconditioning [39,40]. Myocardial preconditioning does exist during
      daily life, explaining the well-known phenomenon of "walk-though angina" and the
      more common "walk-through ischemia." It is hoped that drugs that mimic or enhance
      preconditioning will be developed, which will provide powerful myocardial
      protection.

PMID- 10892399
TI  - Consensus statement on prevention and treatment of osteoporosis.

PMID- 10892400
TI  - Fatal pneumonia due to Bordetella bronchiseptica.

PMID- 10892401
TI  - Isolated unilateral kidney vasculitis.

PMID- 10892402
TI  - Factor V Leiden and the risk of arterial thrombosis.

PMID- 10892403
TI  - Acute bronchitis in hospitalized children.

PMID- 10892404
TI  - Hearts of stone: calcific constrictive pericarditis.

PMID- 10892405
TI  - Endoscopic ultrasound--a major diagnostic tool.

PMID- 10892406
TI  - Polyacrylamide-chitosan hydrogels: in vitro biocompatibility and sustained
      antibiotic release studies.
AB  - Controlled drug delivery is gaining importance over the conventional methods of
      drug administration because of its inherent benefits. Self-regulated release from
      the delivery vehicle may enhance drug potency with a sustained action. The
      present study describes a novel hydrogel blend of polyacrylamide with chitosan
      for controlled delivery of antibiotics. Hydrogel was synthesized by cross-linking
      acrylamide-chitosan mixture (8:2 v/v) with N,N' methylene bisacrylamide. Hydrogel
      was characterized for surface morphology, hydrophilicity, pH-dependent swelling
      properties, cytotoxicity, and control release properties. Scanning electron
      microscopy (SEM) revealed the macroporous surface morphology of the matrix with
      average pore size at 104 +/- 7.61 mu. Hydrogel was found to be highly hydrophilic
      as assessed by octane contact angle (154.5 + 0.572) measurement. Hydrogel showed
      no cytotoxic effects on NIH3T3 and HeLa cells up to 40% of extract concentrations
      as determined by MTT and neutral red assay. This showed hydrogel biocompatibility
      and thus absence of deleterious effects of the hydrogel on cell viability and
      functionality. Hydrogels did not show any pH-dependent swelling profile, and they
      swelled considerably to achieve a swelling ratio of approximately 16.0 at the end
      of 24 hr. Amoxicillin was incorporated in the hydrogel matrix as a candidate
      antibiotic for release studies. In vitro release studies of amoxicillin revealed
      the sustained nature of delivery and matrix released 56.47 + 1.12% and 77.096 +
      1.72% of amoxicillin at the end of 24 and 75 hr, respectively. Although in vivo
      studies are awaited, the present study provides enough documentation to consider
      polyacrylamide-chiotsan hydrogel as a possible candidate for controlled delivery
      of antibiotics.

PMID- 10892407
TI  - Comparison of in vitro and in vivo release characteristics of sustained release
      ofloxacin microspheres.
AB  - The sustained release nature of ofloxacin microspheres--to eradicate bacterial
      biofilm associated with chronic infections from sensitive strains of bacteria-
      was determined both in vitro and in vivo. Ofloxacin microspheres were prepared by
      emulsion solvent evaporation procedure using poly(glycolic acid-co-dl-lactic
      acid) (PLGA) as the biodegradable polymer. The microspheres were characterized by
      scanning electron microscopy, in vitro release in an incubator, and in vivo
      release in the rat subcutaneous model. The microspheres were highly spherical
      with a very smooth surface. Approximately 45% of the drug was released from
      microspheres in sizes of 125-250 microns and 250-425 microns in 2 days compared
      with approximately 22% from microspheres of size range 37-125 microns indicating
      that surface area of the microspheres did not control the kinetics of in vitro
      release. However, about 96% of the drug was released from the three different
      size ranges in 35 days. The in vitro release profile of microspheres of size
      range 125-250 microns is not significantly different from microspheres in sizes
      of 250-425 microns. The peak plasma level of ofloxacin in animals that received
      the drug suspension occurred within 2 hr and was higher than that of the
      microspheres that occurred by the end of the second day. The plasma of animals
      that received the free drug was depleted of ofloxacin by the end of the first
      day, but the drug was sustained above 0.5 microgram/mL in the plasma of animals
      that received the microspheres for about 3 weeks. The results suggest that
      biodegradable ofloxacin microspheres can be prepared that release the antibiotic
      in vivo for about 3 weeks. This should provide a means for continuous treatment
      of chronic infections in which bacterial biofilm can occur.

PMID- 10892408
TI  - In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in
      organophosphorus (OP) antagonism.
AB  - This study describes a new approach for organophosphorous (OP) antidotal
      treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA),
      within sterically stabilized liposomes. The recombinant OPAA enzyme was derived
      from Alteromonas strain JD6. It has broad substrate specificity to a wide range
      of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes
      encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of
      DFP by (SL)* was measured by following an increase of fluoride ion concentration
      using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes
      rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to
      the amount of (SL)* added to the solution. Liposomal carriers containing no
      enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis
      was first order in the substrate. This enzyme carrier system serves as a
      biodegradable protective environment for the recombinant OP-metabolizing enzyme,
      OPAA, resulting in prolongation of enzymatic concentration in the body. These
      studies suggest that the protection of OP intoxication can be strikingly enhanced
      by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.

PMID- 10892409
TI  - Comparative effects of garlic and aspirin on diabetic cardiovascular
      complications.
AB  - By using streptozotocin-induced diabetic rats as a studied model, our previous
      experimental results have indicated that daily oral feeding of garlic extract
      (100 mg/kg BW) could increase the cardiovascular functions in streptozotocin
      (STZ) rats; the abnormality of lipid profile was prevented; and garlic extract
      could increase fibrinolitic activities with the decrease of platelet aggregation.
      Moreover, the plasma insulin level was increased concomitantly with the decrease
      of plasma glucose level. However, due to the high incidence of atherosclerosis in
      diabetes, the present study has been continued for further investigation of the
      effect of garlic extract on the coronary vascular ultrastructural changes. In
      addition, to identify the possible mechanism(s) of garlic's therapeutic effects,
      the cyclooxygenase inhibitor, aspirin, has been included in this present study.
      By using transmission electron microscopic studies, 16 weeks of daily oral
      feeding of garlic extract (100 mg/kg BW) caused as an antiatherosclerotic agent
      at the coronary arteriolar (15-30 microns) wall in STZ-rats. Interestingly, the
      thickening of coronary capillary (5-10 microns) basement membrane also was
      significantly attenuated within the group of STZ-rats treated with garlic
      extract. However, the possible direct action of garlic through the cyclooxygenase
      pathway has not been confirmed by the results of aspirin: The daily oral feeding
      of aspirin (10 mg/kg BW) in 16-week STZ-rats has not showed reduced arteriolar
      vascular wall abnormalities. The irregular patterns of fiber matrix, arranging
      the basement membrane at the arteriolar walls, were still recognized in the same
      manner as in STZ-rats. Interestingly, the thickening of the capillary basement
      membrane occurred in 16-week STZ-rats seems to be attenuated by the aspirin
      received. At present, garlic extract may open the new era in the medicinal use of
      garlic to prevent diabetic cardiovascular complications.

PMID- 10892411
TI  - Concanavalin-A conjugated fine-multiple emulsion loaded with 6-mercaptopurine.
AB  - Fine-multiple (water-in-oil-in-water) emulsions were prepared by two-step
      emulsification using sonication. They were coated with concanavalin-A (Con-A) by
      three methods. The one involving covalent coupling of Con-A to the multiple
      emulsion incorporated anchor was better compared with lipid derivatized Con-A
      anchoring or the glutaraldehyde-based cross-linking method, as shown by the
      faster rate of dextran-induced aggregation. The selected multiple emulsions were
      characterized by physical properties such as droplet size, encapsulation
      efficiency, and zeta potential. Stability parameters such as droplet size,
      creaming, leakage, and aggregation as a function of relative turbidity were
      monitored over a 1-month period, which revealed good stability of the
      formulations. The release profile of 6-mercaptopurine followed zero-order
      kinetics. Pharmacokinetic studies showed an increase in half-life and
      bioavailability from multiple emulsion formulations administered intravenously.
      There was prolonged retention of drug in various tissues of rats when treated
      with Con-A-coated multiple emulsion as compared with uncoated one. Our study
      demonstrates the suitability of fine-multiple emulsion for intravenous
      administration and the potential for prolonged retention of drugs and targeting
      in biological systems.

PMID- 10892410
TI  - Boron-loaded liposomes in the treatment of hepatic metastases: preliminary
      investigation by autoradiography analysis.
AB  - Boronophenylalanine (BPA)-loaded conventional and stabilized liposomes were
      prepared by the reversed phase evaporation method to treat liver metastases by
      boron neutron capture therapy. Conventional vesicles were composed of
      phosphatidylcholine and cholesterol, molar ratio 1:1. To obtain stealth
      liposomes, GM1 or PEG were included in the lipidic bilayer at a concentration of
      6.67 or 5 mol%, respectively. Large unilamellar vesicles were formulated
      encapsulating BPA in the liposome aqueous compartment as a complex with fructose;
      BPA free base also was embedded into the lipidic bilayer. In vivo experiments
      were carried out after intravenous injection of liposome suspensions in BD-IX
      strain rats in which liver metastases had been induced. Alpha particle
      spectroscopy associated with histological analysis was performed to visualize
      boron spatial distribution in liver. Simultaneously, tissue boron concentrations
      were determined using inductively coupled plasma-mass spectroscopy. Results
      showed that PEG-modified liposomes accumulated boron in therapeutic
      concentrations (> 30 micrograms boron/g tissue) in metastatic tissue. The PEG
      liposomes could be further explored in enhancing boron delivery to tumor cells.

PMID- 10892413
TI  - Vive la difference! The international symposium, "Society and Individual
      Predisposition for Successful Pregnancy Outcome".
AB  - A gathering of clinician and epidemiologist researchers from three continents
      assembled in Paris on September 24, 1998, to contribute to a symposium honoring
      Professor Emile Papiernik, Chef de Service de Gynecologie et Obstetrique,
      Maternite Port Royal. The theme was society and individual predisposition for
      successful pregnancy outcome, and each presenter was asked to respond to a
      provocative question posed by Dr. Louis Keith, who presided over the symposium.
      This commentary was prepared shortly after the symposium. It reflects an overview
      of the state of knowledge presented that day by the participating scientists with
      regard to preterm delivery.

PMID- 10892412
TI  - Transdermal delivery of insulin in mice by using lecithin vesicles as a carrier.
AB  - The present study was undertaken to characterize the preparation of flexible
      lecithin vesicles containing insulin and to assess the enhancing effect of these
      flexible vesicles on the transdermal delivery of a hydrophilic protein. Both
      conventional and flexible vesicles were prepared by reverse-phase evaporation and
      treated further by sonication. The free drug was separated from vesicles by
      column chromatography and analyzed by HPLC. Both conventional and flexible
      vesicles were transparent colloidal dispersions. The particle size of the
      conventional and flexible vesicles was 73.5 nm and 87.1 nm with a polydispersity
      index of 44.5% and 15.6%, respectively. The entrapment efficiencies of
      conventional and flexible vesicles were 35% and 81%, respectively. When vesicles
      were nonocclusively applied onto the abdominal mice skin at a dose of 0.90
      IU/cm2, in vivo hypoglycemic study showed the drop percentage of blood glucose by
      flexible vesicles was 21.42 +/- 10.19% at 1 hr, reached 61.48 +/- 8.97% at 5 hr,
      and was larger than 50% within 18 hr. Conventional vesicles, insulin solution,
      and saline had no hypoglycemic effect. Probably due to the incorporation or
      adsorption of a certain amount of insulin into the flexible vesicles during the
      mixing process, blank flexible vesicles mixed with insulin solution had a certain
      degree of hypoglycemic effect, though much less than the effect of flexible
      vesicles containing insulin (p < 0.05). Flexible vesicle may become a promising
      carrier for the transdermal delivery of hydrophilic polypeptides.

PMID- 10892414
TI  - Fetal growth retardation: a limit for the further reduction of preterm births.
AB  - Fetal growth retardation is at present the major obstacle for further reduction
      in preterm births. After 25 years of continuous decline in the preterm birth rate
      in France from 6.9% in 1972 to 4.4% in 1981 and 3.8% in 1989, there has been an
      increase to 4.5% in 1995. The major new fact is the progressive increase of
      medically induced preterm births, mostly related to fetal growth retardation.
      Spontaneous preterm births have continued to decrease throughout all these years.

PMID- 10892415
TI  - Trends and racial differences in birth weight and related survival.
AB  - OBJECTIVE: In the past two decades, infant mortality rates in the United States
      declined in African-American and White populations. Despite this, racial
      disparities in infant mortality rates have increased and rates of low birth
      weight deliveries have shown little change. In this study, we examine temporal
      changes in birth weight distributions, birth weight specific neonatal mortality,
      and the birth weight threshold for an adverse risk of survival within both racial
      groups in order to explore the mechanisms for the disparities in infant mortality
      rates. METHOD: Single live births born to South Carolina resident mothers between
      1975 and 1994 and considered White or African-American based on the mother's
      report of maternal race on the birth certificate were selected for investigation.
      We define the birth weight threshold for adverse survival odds as the birth
      weight at which 50% or more of infants in the population died within the first
      month of life. RESULTS: Despite significant increases in very low birth weight
      percentages, neonatal mortality rates markedly declined. Birth weight specific
      neonatal mortality decreased for both races, although greater reductions accrued
      to White low birth weight infants. By the end of the study period, the birth
      weight at which over 50% of newborns died within the first month of life was 696
      g for Whites and 673 g for African-Americans. DISCUSSION: The ongoing decline in
      neonatal mortality is mainly due to reductions in birth weight specific neonatal
      mortality, probably related to high-risk obstetric and neonatal care.
      Technological developments in these areas may have differentially benefited
      Whites, resulting in an increasing racial disparity in mortality rates. Moreover,
      the relatively greater and increasing mortality risk from postmaturity and
      macrosomia in infants of African-America mothers may further exacerbate the
      racial gap in infant mortality.

PMID- 10892416
TI  - Two types of health care systems and their influence on the introduction of
      perinatal care: an epidemiological twin model in Berlin from 1950 to 1990.
AB  - OBJECTIVES: When perinatal medicine emerged as a new medical discipline in the
      1960s, Berlin was as one of the world's leading centers. During that time, the
      city was separated into two parts, each fostering its own health care system.
      After the destruction of the Berlin Wall, it was possible to speak with the
      citizens of East Berlin and to access their database systems. This created the
      singular opportunity to objectively compare the development of perinatal care in
      both parts of Berlin. METHODS: Rates of maternal, perinatal, and infant mortality
      as well as the rate of preterm deliveries were evaluated over time and between
      East and West Berlin. The timing of introduction of 20 specific perinatal
      interventions was evaluated across 18 hospitals with more than 500 deliveries (11
      in West Berlin and 7 in East Berlin). Interviews were conducted with 100
      gynecologists, 100 midwives, and 100 women who had recently delivered their first
      child from each side of the city regarding their opinions of the importance of
      these interventions for the quality of perinatal medicine and how they would
      distribute a budget to improve maternity care. RESULTS: Maternal, perinatal, and
      infant mortality decreased in both parts of Berlin until 1990 (p < 0.0001),
      without significant differences between East and West Berlin, though the preterm
      delivery rate was slightly lower in East Berlin compared with West Berlin (p <
      0.06). Some new clinical techniques and treatments--such as cardiotocography,
      ultrasound, tocolytic therapy, and peridural anesthesia--were introduced earlier
      in West Berlin. In contrast, certain public health measures--such as maternal
      transport, screening programs for diabetes, and support of breastfeeding--were
      introduced much earlier in East Berlin. There were significant differences
      between the beliefs of gynecologists, midwives, and mothers in East and West
      Berlin. In general, citizens of East Berlin were more enthusiastic about
      technological medical advances, whereas citizens of West Berlin were more
      supportive of public health and alternative methods. In addition, there were
      significant differences between female and male physicians in their beliefs about
      how to improve health care, regardless of whether they resided in East or West
      Berlin. CONCLUSIONS: The results of this study may serve as a basis for
      reflection on how different social circumstances and health care policies can
      influence the improvement of maternal and child health care.

PMID- 10892417
TI  - A retrospective assessment of Canadian preterm birth prevention efforts: 1979
      1999.
AB  - OBJECTIVES: To assess the achievements and effectiveness of efforts to reduce
      preterm deliveries through the collaborative efforts of funding agencies,
      scientists, obstetricians, pediatricians, and health care providers in Canada.
      METHODS: Chronological review of studies carried out in Canada within the past
      two decades using several methodological approaches, including randomized
      clinical trials, surveys of women and physicians, and prospective cohort studies.
      RESULTS: Tertiary prevention by treatment of spontaneous preterm labor with beta
      agonists was effective in delaying delivery by 48 hr compared with placebo.
      Ongoing studies tested the comparative efficacy of oxytocin antagonists to beta
      adrenergic agents. Recently, nitric oxide donors have been tested. Secondary
      prevention using various approaches showed that high-risk factors could not be
      modified by these interventions. Before applying primary prevention approaches,
      surveys disclosed the lack of knowledge among both physicians and pregnant women.
      CONCLUSION: A recent Canadian consensus meeting emphasized the potential for
      success by using multidiscplinary, community-based health promotion approaches to
      prevent preterm labor; enhancing basic research in predictive markers such as
      cervical change, infection/inflammation, and psychosocial stress; and increasing
      political involvement of health decision makers.

PMID- 10892418
TI  - Adverse birth outcomes among native-born and immigrant women: replicating
      national evidence regarding Mexicans at the local level.
AB  - OBJECTIVES: For almost two decades, the literature has consistently described an
      epidemiologic paradox relating to better birth outcomes among high-risk groups,
      particularly new immigrants from Mexico and Southeast Asia. We hypothesize that
      regardless of their sociodemographic profile, Mexican immigrants will exhibit
      lower rates of low birth weight and preterm deliveries than native-(U.S.) born
      women of Mexican origin, non-Hispanic White and Black women, and Puerto Rican
      Women. METHODS: We studied 57,324 live-born singleton infants born to residents
      in the city of Chicago in a linked data set of 1994 birth-death records.
      Multivariate logistic regression was used to analyze race/ethnicity differentials
      in two pregnancy outcome measures, low birth weight and preterm birth. RESULTS:
      Overall better birth outcome is related to maternal immigrant status regardless
      of race/ethnic groups. Immigrant Mexican women had a significantly lower risk of
      both low birth weight [adjusted odds ratio (AOR): 0.78, 95% confidence interval
      (CI) 0.66-0.91] and preterm births (AOR: 0.75, 95% CI 0.65-0.86) and were at 28%
      and 33% lower risks of delivering a low birth weight infant or a premature
      infant, respectively, than non-Hispanic White women.

PMID- 10892420
TI  - Acknowledging the impact of race and ethnicity on better birth outcomes:
      celebrating the work of Emile Papiernik.

PMID- 10892419
TI  - Observations on obstetric practice in a multicultural setting.
AB  - Singapore provides a rich environment for investigations into ethnic differences
      in pregnancy outcome, as it is populated by Malays, Indians, and Chinese. Years
      of clinical practice and obstetric research in this environment have affirmed the
      observation that many factors interact in determining length of gestation and
      birth weight, and that these factors have differential affects among these three
      different ethnic groups. Although technological advances have furthered our
      understanding of obstetrical outcomes and provided essential tools to promote the
      survival of premature infants, the persistent use of uniform growth standards
      hampers our ability to assure positive outcomes for women of different ethnicity.
      Recognition of ethnic differences has resulted in declines in certain negative
      pregnancy outcomes for women in Singapore. The development of race-specific
      uterine growth curves will enhance the provision of perinatal care for all women.

PMID- 10892421
TI  - Hepatitis B virus (HBV) and dual HBV-hepatitis delta virus (HDV) infection in
      apparently healthy persons.
AB  - The main aims of the present study were to evaluate the transfusional risk
      concerning HBV and HBV-HDV infections and the prevalence of viral serum markers
      in apparently healthy persons. Our study included 226 apparently healthy persons
      in whom we performed tests for HBV (HBsAg, HBsAb, HBcAb) and HDV (Delta Ab) serum
      markers, using the enzyme immunoassay. In 45 (19.9%) subjects we detected serum
      HBsAg. In the 181 HBsAg-negative apparently healthy persons, our tests detected
      HBsAb (31 subjects) and HBcAb (49 subjects). Thus, 125 (55.3%) of the 226
      apparently healthy persons had serologic evidence of past HBV infections. Delta
      Ab were detected in 3 (1.3%) of our subjects. We must state that one of the three
      Delta Ab-positive apparently healthy persons tested negative for both HBsAg and
      HBcAb.

PMID- 10892422
TI  - "Trial moves rapidly on, when the judge has determined the sentence beforehand"
      (W. Scott: Ivanhoe, 36) or pitfalls in serosurvey of anti-hepatitis C antibody in
      children.
AB  - Hepatitis C is and will be a major public health concern. Confirmed infections
      were reported from all Romanian counties but important differences between
      regions raise several explanations. Differences may reflect the different levels
      of testing, the performances of laboratories in confirming initially reactive
      samples or the risk factors higher prevalence. We have suggested that the
      prevalence of anti HCV infections can be a surrogate marker for the quality of
      parenteral medical or paramedical interventions. Present report identified
      additional problems in the surveillance of HCV infection in children. We screened
      1787 samples from children hosted in orphanages (children under three years old)
      or in preschool children institutions (between 3-7 years old). We detected 31
      repeatedly reactive samples with two EIA screening kits but confirmed only 8 in
      WB anti HCV. Four confirmed samples come from children under four months old
      suggesting maternally transmitted antibodies. In highly endemic area, many
      infants have maternally derived antibodies and the wane of reactivity comes with
      age above 12 months. Therefore, the prevalence of anti HCV antibody in infants
      reflects the prevalence in adult population. Confirmatory tests are mandatory for
      the serosurvey in children. More frequent than adults samples, children EIA
      reactive samples give indeterminate or negative Western Blot profiles. Only the
      viral load evaluation can confirm those samples as false positive or, on the
      contrary, samples at the beginning of seroconversion.

PMID- 10892423
TI  - Danysz phenomenon in the influenza virus and complement interaction.

PMID- 10892424
TI  - Assessment trials of the therapeutic efficacy of the drug "Zovirax" in some
      recurrent ocular and genital herpetic infections.
AB  - In this work are reported the results of the researches performed by the authors
      more than a decade ago, aimed at assessing the clinical benefit of the
      introduction of the drug "Zovirax" in the treatment of recurrent herpetic
      infections with genital or ocular location. The results of the treatment carried
      out on a restricted group of patients were positive both in cases of genital
      herpes and of herpetic keratitis. The clinical benefit consisted in the reduction
      of the mean duration of the disease, in the shortening of the period of the
      infective virus elimination from the lesion, as well as in the decrease of the
      intensity and duration of the clinical symptomatology as a whole. With respect to
      these clinical parameters, the observations of the authors performed on a low
      number of cases are consistent with the data obtained by other authors in the
      framework of more extensive studies. The renewed discussion of these clinical and
      laboratory observations carried out by the authors during the first years after
      the introduction in our country of this drug in the therapeutic arsenal of
      herpetic infections is aimed at establishing a landmark for the comparison with
      more recent results of similar studies, starting from the idea of the opportunity
      of assessing periodically the sensitivity of herpes simplex virus strains,
      circulating among the autochthonous population, to the inhibitory action of some
      antiviral drugs. In other words, the in vitro testing of the susceptibility of
      these strains to the chemotherapeutic agents in current use is predictive for the
      efficacy degree of these drugs in the treatment of some forms of herpetic
      infections. This evaluation represents at the same time, undoubtedly, a useful
      epidemiological surveillance means of the circulation of human herpes viruses
      among the population. We refer especially to the risk of appearance of
      pharmacoresistant mutants, a risk possible under the conditions of the increased
      access of patients to the antiviral chemotherapeutic medication, which implicitly
      augments the probability of a fortuitous administration of treatments
      insufficient as regards the dose or the duration. In this work there are also
      shown the results regarding some experimental aspects related to the immune
      control mechanisms of the herpetic infection, which may complement the
      chemotherapeutic action. Under the treatment with acycloguanosine the synthesis
      of herpetic antigens is kept at a level sufficient for the circulating antibody
      synthesis induction and the HSV infected cells treated with the drug are
      recognized and lysed by effectors of the cell-mediated immune response of the
      host. Hence, it may be asserted that, in some clinical cases of recurrent herpes
      with frequent episodes, it is useful to perform immunostimulating treatments,
      able to potentiate the cell-mediated immune mechanisms possibly involved in the
      limitation of the herpetic infection at the peripheral level and of its spreading
      in the central nervous system.

PMID- 10892426
TI  - UV-A and PUV-A action on Sendai virus HN glycoprotein.
AB  - The UV-A and PUV-A treatments were applied on the Sendai virus and the changes of
      the biological properties of HN surface glycoprotein were monitorized. Under the
      UV-A action the HA and NA activities are inhibited in a dose-correlated way. When
      the irradiation was done in the presence of a photoreagent (8-MOP) the HA
      activity remained unchanged, but the enzymic activity was affected. The possible
      mechanisms of these inhibition processes are discussed.

PMID- 10892425
TI  - Assessment of the anti-hepatitis B vaccination efficacy in high risk children.
AB  - In October 1995, The Ministry of Health has initiated the national immunization
      program of newborns against hepatitis B. Owing to the frequency of asymptomatic
      Hepatitis B clinical forms in children, as well as the deficiencies in the
      surveillance system, the assessment of the vaccination efficacy can be performed
      objectively only by the detection of the prevalence of anti HBs antibodies in
      children to whom the complete three doses of immunization schedule have been
      administered (at 0, 2 and 6 months of age). We report in this study the results
      of a seroprevalence research carried out on a group of 272 children from
      orphanages who have been vaccinated. A protective anti HBs titer (> 10 mIU) was
      recorded only in 66.3% of cases; other 10 samples contained antibodies at a titer
      lower than the protective level. In the 80 children without seroconversion the
      presence of anti HBc antibodies (marker for the natural infection) was
      investigated. 30% of the seronegative children have anti HBc antibodies from
      which 54.2% have also HbsAg. Significant differences were recorded in the
      seroconversion level and in the geometric mean of titers between the various
      units in which sera were collected. In four orphanages (district Arad, Jassy,
      Sibiu and Teleorman) the seroconversion exceeded 90%, in 5 orphanages it was over
      80% and in the others it ranged from 30% to 70%. The lowest seroconversions were
      recorded in the orphanages in Bucharest, Botosani, Galati and Olt. The possible
      causes of the low immunogenicity are analyzed: non-vaccination or incomplete
      vaccination; low immunoreactivity of children, many of whom are premature; high
      HbsAg carriage rate among the mother's etc. Although the evolution of the post
      vaccinal seroconversion is not a routine practice in the appraisement of
      Hepatitis B vaccine immunogenicity, our results require the extension of the
      study in order to adopt the most effective vaccinal strategy.

PMID- 10892427
TI  - Cerebrospinal fluid western Blot profiles in the evolution of HIV-1 pediatric
      encephalopathy.
AB  - In order to obtain information on neurologic AIDS, 54 white caucasian children
      infected by nosocomial route with a median age of 46.2 +/- 7 months were followed
      up prospectively for a median of 12 months with three months Denver tests
      neurologic evaluation and six months serologic investigations in CSF and sera.
      Paired CSF and serum samples, collected on the same day, from children with AIDS
      encephalopathy, were analysed for the permeability of the blood brain barrier
      (BBB) and for intrathecal production of anti HIV specific antibodies. A
      prospective follow-up and repeated comparison of WB profiles and the presence of
      anti V3 antibodies in CSF and sera was done, as well as an evaluation of the
      modification in the CSF antibody specificity (anti gag Western Blot scoring) with
      disease progression. An increased intrathecal synthesis of IgG was recorded in
      all subjects, in spite of an unaltered BBB permeability. No significant
      differences were recorded for the anti gag score in the serum samples, which was
      stable between 9.1-10.4. By contrast, the score for CSF samples decreases
      significantly with disease progression, from 8.7 in children without
      encephalopathy, to 6.5 in those with stationary disease and 3.6 in the
      progressive encephalopathy group. A strong correlation was found between the
      level of anti p24 antibodies determined by ELISA and the anti gag score
      quantified by WB for the same CSF samples. The p24 antigen was found to be
      positive only in 3 cases, even after immune complex dissociation. Anti V3
      antibodies were not detected in CSF samples from patients with functional BBB.
      The decline in anti-gag antibody reactivity in CSF is an early indicator of
      disease progression, reflecting a severe course of neurological impairments. The
      absence of anti V3 antibodies in the CSF samples suggests that the PND of
      neurotropic strains mapped in distinct positions into the V3 loop. These results
      reflect the selection of antigenic escape mutants which evolve in the CNS,
      distinct from the blood lymphotropic isolates.

PMID- 10892428
TI  - Low rates of seroconversion after hepatitis B vaccination in orphanges with high
      prevalence of virus carriers.
AB  - A serosurvey of Hepatitis B infection markers was conducted in two orphanages
      that adhered to Hepatitis B vaccination policy. In spite of comparable sizes (80
      90 children per facility), housing conditions and infection control practices,
      the level of HbsAg endemicity was different in each unit in direct relation with
      the mean age of the children. The prevalence of HbsAg carriers and the interval
      spent in collectivity strongly affect the seroconversion rate after HB
      vaccination. Other elements that can explain the low seroconversion rate were:
      the proportion on fully vaccinated children, the number of vaccine administered
      doses and the delayed age at which childhood immunization schedule was initiated.
      In order to increase the protective antibody response, booster doses were
      administered to a limited number of nonseroconvertors or to children with a
      nonprotective level of anti-HBs antibody (< 10 UI). This intervention provides
      evidence of prompt rising in antibody titers, comparable with titers found in
      children with wild infection.

PMID- 10892429
TI  - Human papillomavirus and human cytomegalovirus DNAs presence in patients
      suspected of condylomatosis or papillomatosis.
AB  - 17 samples of total cell DNA isolated from cervical smears from women suspected
      of condyloma or papilloma were analysed by PCR with appropriate primers, in order
      to establish the presence of viral DNAs (HPV and/or HCMV). HPV DNA was found in
      seven cases, and so was for HCMV DNA. Only in three cases a coinfection was
      present. The RFLP allowed to specify the involvement of HPV6 in 3 cases suspected
      of condyloma and in one suspected of papilloma; the other three HPV positive
      samples had another genotype, which we could not determine by the methods used.

PMID- 10892430
TI  - Human immunodeficiency virus types 1 and 2 infection in some rural areas of
      Nigeria.
AB  - The prevalence of human immunodeficiency virus types 1 and 2 in rural areas of
      Nigeria was estimated using 1089 sera collected in 18 locations from 1992 to
      early 1994. The sera were tested with Enzyme linked Immunosorbent Assay (ELISA)
      and confirmed by Western Immunoblotting technique. Overall, 13 (1.2%) of the 1089
      sera were positive for antibodies to HIV-1 and HIV-2. Prevalence of 0.6% and 0.8%
      were obtained for HIV-1 and HIV-2 respectively. The highest prevalence of HIV-1
      and HIV-2 (50.0%) were found in Zuhlrrua and Umubuzu. A seroprevalence of 1.2%
      was obtained for both male and female groups tested. The highest prevalence of
      HIV was found among individuals 30-39 years age group. An overall increase in
      prevalence of HIV-1 and HIV-2 infection was obtained over the three years during
      which samples were collected for this study (0.7% in 1992, 1.0% in 1992 and 3.4%
      in 1994). In addition, two sera were positive for both HIV-1 and HIV-2. The
      detection of antibodies to HIV-1 and HIV-2 in the rural areas where blood samples
      were collected for this study shows that both viruses are widespread in the rural
      communities of Nigeria.

PMID- 10892431
TI  - Immunogenicity of inactivated vaccines prepared with parainfluenza viruses type 1
      and type 3, administered experimentally by nasal or oral route.
AB  - The inactivated vaccines prepared with parainfluenza viruses type 1 and type 3,
      administered to mice by nasal or oral route, either as monovalent preparations in
      succession or as bivalent associated preparations according to the experimental
      models used, imparted a significant protection against the infection with the
      homologous active viruses. The routes of administration of vaccines, nasal and
      oral, which make equal demands upon the immune secretory serum and cell system,
      as well as the alternative of inactivated preparations for active virus vaccines
      are discussed.

PMID- 10892432
TI  - Observations regarding the neurocytokaryological study of the experimental
      infection with herpes simplex virus type 1 and type 2 in the white mouse.
AB  - Mice distributed in groups were inoculated with the herpes virus simplex type 1
      and type 2 strains in various dilutions (10(-1)-10(-7)), which had been
      maintained on primary human embryo cell cultures. The animals were killed and
      homogenates were prepared of their brains, which were used for testing the
      infective titre in vivo and for the isolation of nuclei, by means of the Hymer
      Kuff technique. For the cytokaryological examinations, smears were prepared from
      the homogenate, which were stained by May-Grunwald-Giemsa and Mann methods. The
      cell and nucleus types were evaluated morphologically, descriptively, according
      to the size and structure. On the basis of three criteria the following groups
      were set up: large sized cells with bulky nuclei; middle sized cells with nuclei
      of a medium size; small sized cells with small nuclei and visible nucleoli; small
      sized cells with small, tachychromatic nuclei; cells exhibiting karyolysis. In
      both the infection with herpes virus simplex type 1 and type 2, the small sized
      cells with small tachychromatic nuclei represent the highest rate. Between the
      variants of the elaborated models no significant differences regarding the cell
      and nucleus types are recorded. On the whole, the cytokaryological picture does
      not exhibit notable differences, but rather resemblances with respect to the
      proportionality of the nucleus types in the experimental variants studied, in the
      case of herpes simplex virus type 1 and 2 induced infections.

PMID- 10892433
TI  - [Rickettsia infections in Portugal].
AB  - After a brief introduction about rickettsioses, we analyse Mediterranean Spotted
      Fever (MSF) in Portugal, and review Portuguese medical literature. We focussed on
      the seasonal summer pattern of the disease. MSF is very frequent in Portugal,
      nearly 1,000 cases are reported every year and young age groups are the most
      afflicted. Although usually regarded as a benign condition, MSF has emerged as a
      potentially lethal disease in recent years. The clinical presentation is protean,
      but usually suggestive enough to allow a clinical diagnosis. The complications
      are well documented, elderly and people with chronic debilitating diseases being
      the most affected. Q fever is also endemic in Portugal, although with more modest
      numbers (about 50 cases a year). Serological studies, however, suggest a higher
      incidence, probably because the disease is unfamiliar to many clinicians and, as
      such, it is difficult to diagnose and, consequently, then an important number of
      subclinical or self-limited cases. In Portugal, fever with hepatic involvement is
      the most common clinical presentation. Other less frequent clinical forms are
      atypical pneumonia and CNS involvement. Chronic Q fever is a rare condition.

PMID- 10892434
TI  - [Brucellosis].
AB  - Brucellosis is a zoonosis, reported for the first time in 1859 by Marston, in
      Malta. It has also been referred to as Mediterranean Fever, Malta Fever and
      Bang's disease. Its causative agent was isolated by David Bruce in 1886; this was
      Brucella melitensis: five different strains were later described: B. abortus, B.
      suis, B. ovis, B. neotomae and B. canis. Recently, in 1994, the isolation of
      Brucella was reported in marine mammals, eventually pathogenic to man and
      unofficially designated "B. maris". Human brucellosis is still a public health
      problem in countries where the infection has not been eradicated from the animal
      hosts. When manifested, human disease may assume different courses, widely known,
      but whose physiopathology is still not totally clear. Much is already known about
      the agent's molecular biology and in vitro behaviour, but, doubts persist about
      its in vivo activity, including in human infection. We review some aspects of
      brucellosis, focusing on the pathogenesis, and referring to new and potential
      diagnostic methods, therapy and prevention.

PMID- 10892435
TI  - [Human leptospirosis. A short review concerning a caseload].
AB  - Leptospirosis, a zoonosis with worldwide distribution, may have a broad spectrum
      of clinical manifestations that can delay the diagnosis, especially in wet
      climates where other conditions may dissimulate the main aspects. The authors
      describe 42 cases of patients with leptospirosis admitted to the Infectious
      Diseases Unit of a general hospital since 1990. The goal was to analyse
      epidemiological features, clinical manifestations, laboratory findings, treatment
      and evolution. There were 23 males (54.7%) and 19 females (45.2%), with ages
      ranging from 17 to 82 years. Most cases occurred in occupational settings,
      especially in those in contact with animals or stagnant water. All the cases had
      serological confirmation (by MAT or ELISA methods). Anicteric forms represented
      42.9% of the total, which implies that in many cases a diagnosis is not
      immediately evident. The main symptoms, other than fever (97.6%) and jaundice
      (57.1%), were myalgia (71.4%), headache (42.8%) and nausea (33.3%). Renal
      involvement was common (52%), but the most severe forms occurred in 3 patients
      who required hemodialysis; followed by D.I.C. in 9.5%; meningitis in 4.7% and
      pulmonary involvement in 2.3% of the cases. The serovars most commonly identified
      were L. icterohaemorraghiae (28.5%), L. australis (14.3%), L. grippothyphosa
      (11.9%) and L. canicola (9.5%). The patients were treated with penicillin G
      (83.3%) or doxycyclin (9.5%). Two of them deceased (4.7%) and the remainder had a
      good evolution. The diagnosis of leptospirosis may be delayed if physicians fail
      to include this infection in the initial differential diagnosis. In view of this,
      the authors emphasize that when nonspecific clinical manifestations occur, a good
      epidemiological history is useful in proposing this diagnosis.

PMID- 10892436
TI  - [Etiologic diagnosis of viral meningitis. Study of 142 cases].
AB  - Viral meningitis is a common disease, most often benign and striking
      predominantly children. In 1997, there was an outbreak of viral meningitis in the
      North of Portugal and this pathology accounted for 496 admissions to the
      Infectious Diseases Department of S. Joao Hospital. The authors' aim was to
      determine the etiology of the cases of viral meningitis admitted to the S. Joao
      Hospital by, in a first phase, searching enterovirus and serology for mumps in a
      sample of 142 patients with symptoms, signs and cerebrospinal fluid (CSF)
      cytochemical abnormalities typical of viral meningitis, in the absence of any
      bacterial or fungal growth (in blood and/or CSF) and with negative soluble
      bacterial antigens in CSF. The enterovirus was detected by polymerase chain
      reaction (PCR) and, in a small number of cases, by shell vial culture. The
      diagnosis of mumps was made by the detection of specific IgM antibodies in serum,
      using an enzyme-linked immunosorbent assay. The diagnosis was reached in 70
      patients (49.3%): 47 (33.1%) had mumps meningitis and 23 (16.2%) enterovirus
      infection (PCR positive in all; culture positive in only 2 cases). In 72 patients
      (50.7%), the agent was not identified. Although only two agents were searched
      for, the diagnosis was made in a high proportion of cases. The culture method
      used for the isolation of enterovirus was found to have a low sensitivity.

PMID- 10892437
TI  - [Liver involvement in HIV infection and various parasitic diseases].
AB  - During the course of systemic infections, the liver is an organ which is
      frequently involved. The pathology of the human immunodeficiency virus with all
      its infections, opportunistic tumours and some parasitoses, such as amebiasis,
      kala-azar, hydatidosis, schistosomiasis and fascioliasis, evolve into hepatic
      compromise. This development is what we attempt to summarise.

PMID- 10892438
TI  - [Kaposi sarcoma associated with HIV infection].
AB  - Kaposi's sarcoma is the most common neoplasm in AIDS patients. In a 12-year
      period, 45 (8%) cases were diagnosed in 552 patients with AIDS. Epidemiological
      and clinical aspects are reviewed. The disease occurred predominantly in males
      and homosexuals. In 30 (67%) patients it was the first manifestation of AIDS.
      Skin and/or oral disease was the most frequent manifestation observed in our
      patients; 13 (29%) had visceral involvement. Previous or concommitant
      opportunistic diseases, systemic illness and severe immunosuppression were
      present in the majority of the patients. Opportunistic infections were the cause
      of death in 30 patients; in five others, Kaposi's sarcoma was responsible for
      death. Advances in antiretroviral therapy were of benefit for patients submitted
      to chemotherapy and may contribute to a reduction in morbidity with this
      neoplasm.

PMID- 10892439
TI  - [Human immunodeficiency virus type 2 infection].
AB  - The isolation of a second retrovirus, HIV-2, led to fears that a second AIDS
      pandemic, similar in scope and magnitude to that caused by HIV-1, might ensue.
      However, the peculiar biologic properties of HIV-2, namely the lower
      transmissibility of this virus through both sexual and vertical routes,
      contributed to a more regionalized distribution of the virus, which became
      endemic in West Africa. HIV-2 is genetically more closely related to SIV than to
      HIV-1. When it comes to clinical disease, the spectrum of opportunistic
      infections and tumors (except for Kaposi sarcoma) are similar to that observed
      with HIV-1. Controlled longitudinal studies suggest that the rate of progression
      to advanced HIV related disease and mortality are far lower for HIV-2 than for
      HIV-1. Understanding how, immunologically and virologically, HIV-2 behaves
      differently from HIV-1 may provide some insight into the mechanisms governing HIV
      1 pathogenesis.

PMID- 10892440
TI  - [Atypical mycobacteria infections].
AB  - The isolation of nontuberculous mycobacteria was considered for many years as a
      result of contamination or transient colonization. The role of these bacteria in
      human disease was recognized only after 1950. They were present almost
      exclusively in patients with underlying pulmonary pathology and were rare. The
      prevalence of disease caused by nontuberculous mycobacteria was dramatically
      increased with the AIDS epidemic. Disseminated infection with MAC and other
      atypical mycobacteria is nowadays a frequent complication of AIDS. The authors
      describe some epidemiological and clinical features of these nontuberculous
      mycobacteria emphasizing the role of MAC and make some considerations about the
      diagnosis, prophylaxis and treatment of these diseases. The authors end by
      presenting their own clinical experience.

PMID- 10892441
TI  - [Infective endocarditis].
AB  - Two different series of patients with Infectious Endocarditis (IE), hospitalized
      in the same ward of Curry Cabral Hospital in Lisbon, are presented and compared.
      The two series were separated by a ten-year period--the first included patients
      observed from 1970 to 1976 and the second from 1988 to 1998. In the first series
      (20 patients), IE occurred mainly in patients with previous cardiac valvular
      lesion, the course was subacute and Streptococcus viridans was the predominant
      agent. In the last series (65 patients), most of the patients were young and had
      no previous valvular lesions. Right side endocarditis predominated and the course
      was acute. Most of patients were drug addicts and had HIV infection.
      Staphylococcus aureus was the predominant agent. The ages of the two series were
      significantly different (p < 0.005). The diagnostic value of transthoracic and
      transesophageal echocardiography is stressed. The details of the evolution of
      patients with HIV infection are presented according to the values of CD4+
      lymphocyte counts. The relatively good prognosis of IE in drug addicts with
      antibiotic treatment, even with HIV infection, is emphasized.

PMID- 10892442
TI  - [Activities at an Infectious Disease Intensive Care Unit (1988-1997)].
AB  - The practice of an Infectious Diseases Intensive Care Unit for a period of ten
      years (1988-1997) is reviewed. In this time 1,191 patients were treated--822 had
      more than 15 years of age and 369 were younger. The occupation rate ranged
      between 74.4% and 90.8%, and the mean patient stay in the UCI ranged between 6.7
      and 12.5 days. Nine hundred and forty-four patients were discharged cured or
      improved during the stay and 247 (20.7%) died. The most frequent pathologies
      were: meningitis--371 patients (33.6%); encephalitis--103 (8.6%); and tetanus 143
      (12.0%) patients. The morbidity and mortality of different pathologies admitted
      to the Intensive Care Unit are presented. The mortality rate of the two most
      common diseases (meningitis and tetanus) is discussed. The need for Intensive
      Care in the field of Infectious Diseases is stressed.

PMID- 10892443
TI  - [Various criteria for the choice of the empirical antibiotic treatment of
      pneumonia in intensive care].
AB  - In this paper we present a synopsis of the recommendations of three Consensus
      Conferences (from the American Thoracic Society and the American Society of
      Infectious Diseases) for the empirical antibiotic treatment of severe community
      and hospital acquired pneumonia. Several groups are defined according to the
      existence of specific risk factors, severity of the disease and timing of the
      onset of pneumonia (in the case of nosocomial pneumonia). Each group has more
      likely pathogens and several antimicrobial agents are proposed. However the
      option must always rely on the local microbiological sensitivity pattern.

PMID- 10892444
TI  - Physiological variability arising from in vitro propagation of Nothofagus
      obliqua.
AB  - As with cuttings, the microcuttings produced from in vitro generated shoots could
      be affected by topophysis. Very little research has been done about such in vitro
      effect. This paper reports the influence of the topophysis on the regeneration
      response (shoot multiplication, microcutting rooting and plantlet acclimation) of
      explants on the in vitro culture of juvenile N. obliqua trees. The results showed
      that the main responsible of the physiological variability arising from all the
      in vitro propagation stages is topophysis. This influence was found in the first
      culture and can be extended to the next subculture (multiplication stage). Growth
      of the obtained plants was also affected (rooting of microcuttings and plantlet
      acclimation). The multiplication rate was lower in apical portion (1:3.66) than
      basal portion (1:5.8) while rooting was 48.6% and 27.0% respectively. By the way,
      length of acclimated explants was 52.4 mm in the apical rooted explants and 28.7
      mm in the basal ones at the 30th day. In order to reduce such variability, it is
      necessary to take into account the initial position of the explants during the
      establishment and multiplication stages of micropropagation of forest trees.

PMID- 10892445
TI  - Superovulation in vesper mouse Calomys musculinus (Rodentia-Sigmodontinae).
AB  - Optimal conditions for pharmacological induction of ovulation of vesper mouse,
      Calomys musculinus, were analyzed. The best superovulation (a mean of about 21
      eggs per female, range 12-45) was induced by the administration of 12 IU of PMSG
      followed 48 hr later by injection of 15 IU of hCG. Ovulation started about 10 hr
      after administration of hCG and was completed during the next 4-5 hr. The
      induction of ovulation was achieved irrespective of the stage of the oestrus
      cycle at the moment of PMSG administration. The majority of females (105, 82.7%)
      responded to the treatment with either an ovulatory (53.4%) or superovulatory
      (49.7%) response. Oocyte recovery and egg quality were clearly influenced by the
      age of females, 30 days to more than 120 days old. The majority (90.3%) of
      superovulated eggs was morphologically normal, and only a small proportion of
      eggs showed morphological abnormalities (7.4%) or were spontaneously activated
      (2.3%). Superovulated oocytes under these conditions, were able to undergo normal
      fertilization in vitro. After 6 hr of sperm-egg interaction in vitro, 87.5% of
      the oocytes had extruded the second polar body and/or developed pronuclei.

PMID- 10892446
TI  - Isolation of a frog lectin using polylysine to reduce non-specific interactions
      with heparin binding ligand.
AB  - Polylysine is a polycation used in histology to glue tissue sections to glass
      slides. It was successfully used to eliminate positively charged proteins from
      heparin-agarose beds applied for affinity chromatography facilitating the
      preparative steps in the isolation and purification of heparin binding lectins
      from the ovary of the frog Leptodactylus occellatus. The addition pretreatment of
      agarose-heparin beds with polylysine increased more than 3-fold the
      hemagglutinating capacity of eluted lectin.

PMID- 10892447
TI  - Morphological and cytochemical changes during nuclear maturation in Bufo arenarum
      oocytes.
AB  - The morphological and cytochemical changes undergone by the oocyte during
      progesterone-induced nuclear maturation were analyzed in fully grown follicle
      oocytes of Bufo arenarum during the breeding period. The distribution and the
      staining properties of the nuclear material and of the perinuclear cytoplasm were
      studied. Our observations indicate that, during this complex process, the
      germinal vesicle (GV) undergoes migration and dissolution. The nuclear sap, which
      in the control has an homogeneous aspect, during maturation adopts a fibrillar
      appearance in the basal zone, showing basophilia and positive reaction to PAS,
      Feulgen and Methyl green-Pyronin staining. When the GV breakdown occurs, the
      nuclear contents become mixed with the cortical cytoplasm, developing a different
      cytoplasmic mass that disappears about 12 h after the beginning of incubation.
      The perinuclear cytoplasm exhibits metachromasia and orthochromasia with
      Toluidine Blue at pH 5.6 and a strong basophilia with PAS, suggesting the
      existence of acid compounds. The presence of nucleic acids such as RNA and DNA is
      a strong possibility because of the positive reaction to Methyl green-Pyronin,
      Feulgen and DAPI. This cytoplasmic mass remains until the end of the meiotic
      resumption process.

PMID- 10892448
TI  - First demonstration of the substructure of recombination nodules.
AB  - Recombination nodules are submicroscopic structures that are found in all the
      sexually reproducing, eukaryotic organisms during the pachytene stage of meiotic
      prophase I. Despite many reports on their number and location, no definite
      substructure was previously reported in these nodules. The present observations
      on spread oocytes and spermatocytes of the pigeon, using an improved technique
      for protein preservation, shown the presence of particulate subunits or
      "recombinomeres" in late recombination nodules, besides an interparticle matrix.
      The number of subunits per each nodule ranges from 1 to 5, and this number
      increases with the advancement of pachytene substages. These subunits are present
      in recombination nodules of all the other avian species previously studied, and
      they may be present in other organisms as well. It is suggested that the
      particulate substructure of recombination nodules mirrors the multiplicity of
      multienzymatic complexes that are needed for the ordered series of reactions that
      occur at the molecular level in the sites of meiotic recombination.

PMID- 10892449
TI  - Structure of the Bufo arenarum kidney: renal corpuscle, neck segment and proximal
      tubule.
AB  - The structural organization of the renal corpuscle (RC), ciliated neck segment
      (NS) and the proximal tubule (PT) were studied in the toad, Bufo arenarum, by
      means of light and transmission electron microscopy. The ciliated neck segment
      and the proximal tubule are located in the dorsolateral zone of the kidney, while
      the distal tubules are located in a ventromedial zone. RC are found between these
      two zones. The glomerular filter apparatus consists of the podocyte epithelium, a
      basement membrane, a subendothelial space and an endothelium. The podocyte emits
      cytoplasmatic processes extending over the surface of the glomerular capillaries.
      These processes divide into further processes ending in expansions known as
      pediceles. The basement membrane consists of a lamina rara externa and a rather
      thin lamina densa, while the subendothelial space contains collagen fibers and
      slender cytoplasmic processes of the mesangial cells. NS are composed of ciliated
      cells with a characteristic location of the mitochondria. The PT consists of
      prismatic cells with a dense luminal brush border of long microvilli and numerous
      apical vesicles. The basal cell membrane is increased by small infoldings. One
      characteristic structure of the cytoplasm is the presence of lipid droplets. The
      cytological structure of PT cells can be considered as an adaptation for the
      reabsorption of organic materials.

PMID- 10892450
TI  - Immunohistochemical and ultrastructural age-related changes in rat lactotroph
      cells.
AB  - Ageing produces alterations in some functions of the hypothalamo-pituitary axis
      leading to sexually dimorphic changes in the prolactin (PRL)-secreting cells.
      Since quantitative morphological data of these age-associated alterations are
      scarce, we carried out a morphometric immunohistochemical assessment as well as
      an ultrastructural study of the PRL cell population in male and female rats of
      different ages. Young (3-month-old), old (20-month-old), and senescent (31-month
      old) Sprague-Dawley rats of both sexes were sacrificed by rapid decapitation,
      their pituitaries immediately dissected out and processed for both
      immunohistochemistry and electron microscopy. Analysis of different morphometric
      parameters revealed that the cell density (CD) and volume density (VD)
      significantly decreased with age in male rats. In females, while CD showed a
      significant age-related diminution when young rats were compared to old ones,
      this parameter increased in senescent animals. The VD presented higher values in
      senescent rats. When the data were compared between sexes, VD was found to be
      higher in females if old and senescent rats were considered. Finally, CD
      increased significantly in females when compared to males. The ultrastructure of
      the PRL cells from old and senescent animals of both sexes exhibited changes
      suggestive of an hyperstimulation state, with some prolactotrophs having the
      appearance of cells undergoing an involutive process. We conclude that ageing has
      a differential impact on the PRL cells of male and female rats with respect to
      the immunohistochemical and ultrastructural features of that cell population.

PMID- 10892451
TI  - A simple method for taking photographs of histological sections without using
      neither photographic camera nor microscope.
AB  - A simple photographic method for histological sections is described. This is a
      contact method which does not require the use of photographic camera. It is very
      similar to the contact print method used routinely in photographic laboratories.
      It is performed by placing the slides with the histological section, coverslip
      downwards, over the emulsion of the negative film. Then, they are illuminated
      with a common photographic enlarger during a brief period of time. Thus, a
      negative contact print of the section is obtained. This technique yields
      photographs of high quality focus, sharply contrasted with great detail. These
      results may also be obtained with low-contrast stained sections. This method is
      most suitable for photography of large or medium-sized histological sections
      (macros). This is often the case of neuroanatomical and immunohistochemical
      studies. Our method, being simple and quick, is recommended for routine use in
      laboratories.

PMID- 10892452
TI  - Epidemiological features of drug resistant tuberculosis in Harare, 1994 to 1996.
AB  - OBJECTIVES: To characterise the prevalence, clinical and radiological features of
      drug resistant tuberculosis in selected patients with pulmonary tuberculosis in
      Harare between 1994 and 1996. DESIGN: A retrospective review of medical and
      microbiological records. SETTING: Beatrice Road Infectious Diseases Hospital,
      Harare, Zimbabwe. SUBJECTS: 381 smear-positive tuberculosis patients who had
      samples submitted to the National Tuberculosis Reference Laboratory for culture
      and susceptibility testing. MAIN OUTCOME MEASURES: Prevalence of resistance of
      isolated cultures of Mycobacterium tuberculosis to anti-tuberculosis drugs;
      clinical, radiological and microbiological response to treatment with recommended
      anti-tuberculosis regimens. RESULTS: Resistance to one or more drugs was detected
      in 16 isolates (16/165, 9.7%), single drug resistance in five (3.0%) and
      resistance to two or more drugs in 11 (6.7%). There were no distinctive clinical
      or radiological features of drug-resistant tuberculosis, although a higher
      percent of drug resistant cases had evidence of pleural disease (25% vs 2.5%, p =
      0.005). Neither past history of tuberculosis or known or suspected HIV infection
      was associated with the presence of drug resistance. CONCLUSIONS: In spite of the
      resurgence of tuberculosis and the high prevalence of HIV infection in Zimbabwe,
      the rates of drug resistance have remained relatively low, even among a selected
      population at high risk of resistance. A significant proportion of cases of drug
      resistant tuberculosis appear to be due to new transmission of drug resistant
      strains, which reinforces the importance of maintaining a surveillance system for
      the monitoring of drug susceptibility. Ongoing prospective studies should provide
      more reliable estimates of the prevalence and determinants of drug resistance in
      Zimbabwe.

PMID- 10892453
TI  - Prescribing patterns for the use of antithrombotics in the management of atrial
      fibrillation in Zimbabwe.
AB  - OBJECTIVES: To assess the prescribing patterns for the use of antithrombotics in
      the management of atrial fibrillation. DESIGN: A descriptive cross sectional
      study. SETTING: Parirenyatwa Hospital, Harare, Zimbabwe. SUBJECTS: The outpatient
      records of 200 outpatients attending the cardiac clinic (with a documented
      history of an irregular pulse) between January and August 1999 at Parirenyatwa
      Hospital, Harare, Zimbabwe were reviewed. MAIN OUTCOME MEASURES: In addition to
      antithrombotic therapy prescribed at the time of review, patient information
      (rural or urban), relative contra-indications to antithrombotic therapy, and risk
      factors for stroke were identified. RESULTS: Patients were similar in terms of
      age, sex, and risk factors for stroke. At least one stroke risk factor was noted
      in 79% of urban and 83% of rural patients. Two risk factors were noted in 26% of
      patients. It was noted that urban patients were more likely to have a relative
      contra-indication to antithrombotic therapy compared with rural patients (24% vs
      10%, p = 0.028) but received antithrombotic therapy more often (38% vs 19%, p =
      0.025). CONCLUSIONS: Patients with atrial fibrillation are being inappropriately
      managed in terms of their major prognostic risk factor. Rural patients with
      atrial fibrillation receive antithrombotic therapy less frequently than urban
      patients despite having a similar high risk profile and fewer relative contra
      indications.

PMID- 10892454
TI  - Microalbuminuria in a clinic population of type 2 Melanesian diabetics:
      relationship to glycaemic control, blood pressure and duration of diabetes.
AB  - OBJECTIVE: To determine the prevalence of mcroalbuminuria in type 2 diabetes from
      Papua new Guinea and examine its association with glycaemic control, blood
      pressure and duration of diabetes. DESIGN: Prospective, type 2 Melanesian
      diabetics attending a diabetic clinic. SETTING: 800 bed teaching hospital in Port
      Moresby, Papua New Guinea. MAIN OUTCOME MEASURES: Microalbuminuria, glycaemic
      control, systolic and diastolic blood pressure, serum creatinine, duration of
      diabetes. RESULTS: Microalbuminuria was detected in 42% (34 males and 37 females
      of mean age 41 years) with significantly (p = 0.007) higher values being observed
      in males. Hypertension was present in 16.9% of diabetics. Both systolic and
      diastolic blood pressure measurements were significantly higher in diabetics with
      microalbuminuria. There were no significant differences in age, Body Mass Index
      (BMI), and glycaemic control in patients with or without microalbuminuria. On
      regression analysis, the presence of microalbuminuria was found to be independent
      of glycaemic control, duration of disease, (BMI), but influenced strongly by
      diastolic blood pressure (p = 0.002) and to a lesser degree by age (p = 0.043).
      CONCLUSION: There was a high prevalence of mcroalbuminuria, which was independent
      of glycaemic control, BMI and duration of disease. The presence of
      microalbuminuria was influenced by diastolic blood pressure and age. Patients
      with elevated creatinine levels were also found to be at risk.

PMID- 10892455
TI  - Antenatal care patterns and factors associated with perinatal outcome in two
      rural districts in Zimbabwe.
AB  - OBJECTIVE: To study antenatal care (ANC) patterns, to identify factors associated
      with poor perinatal outcome and quality of ANC. DESIGN: Cross sectional community
      based survey. SETTING: Murewa and Madziwa rural Districts. SUBJECTS: 644 women
      aged between 15 to 50 years who had been pregnant in the immediate 24 months
      preceding the survey. MAIN OUTCOME MEASURES: Perinatal outcome, ANC attendance,
      distance from health centre, ability to pay for ANC, gestation at first booking,
      frequency of ANC visits, use of herbs in pregnancy, pregnancy related morbidity
      and quality of ANC. RESULTS: A total of 644 women were interviewed. Overall
      perinatal mortality was 115 per 1,000 births. 511/644 (79.3%) visited a health
      centre for ANC. The woman herself (41.8%) as well as husbands (41.8%) were
      commonly the decision makers regarding starting ANC. Only 298/510 (58.4%) of
      women used primary health care facilities for ANC. 211/629 (35.1%) of women lived
      more than 5 kms from the health care centre. 153/629 (24.3%) were not able to pay
      for ANC. Only 110/509 (21.6%) started ANC in the first trimester. 307/495 (62.0%)
      made five or less ANC visits. Pregnancy related morbidity was high 209/644
      (32.5%) and use of traditional herbs was common 158/644 (24.%). There were
      significant differences between districts as far as perinatal outcome, ANC
      attendance, distance from health centre, ability to pay for ANC, gestation at
      first booking, frequency of ANC visits, use of herbs in pregnancy, pregnancy
      related morbidity and quality of care all having p values of 0.001 or less. On
      further analysis using logistic regression, having problems with pregnancy and
      vaginal bleeding were significant predictors of poor perinatal outcome with odds
      ratio (95% CI) of 2.8 (1.4 to 5.9) and 3.0 (1.1 to 8.6) respectively. Quality of
      ANC was rated as sub-optimal. CONCLUSION: Majority of rural women attended
      clinics for ANC. Perinatal mortality rate and pregnancy related morbidity were
      high. Vaginal bleeding was the strongest predictor for mortality. There is need
      to improve quality of antenatal care as this was found to be suboptimal. More
      objective oriented antenatal care visits and waiting mother's shelters form part
      of the solutions. Further studies are called for.

PMID- 10892456
TI  - Serum immunoglobulin levels in paediatric patients with pneumonia.
AB  - OBJECTIVE: To determine levels of serum immunoglobulins IgG, IgM and IgA in
      patients admitted with pneumonia to Harare Central Hospital paediatric wards.
      DESIGN: A cross sectional pilot study. SETTING: Harare Central Hospital,
      Department of Immunology, University of Zimbabwe; Department of Paediatrics,
      University of Zimbabwe; Immunology Laboratory, University of Utrecht (The
      Netherlands). SUBJECTS: 71 paediatric patients. MAIN OUTCOME MEASURES:
      Immunoglobulin profiles for children with pneumonia. RESULTS: Of the 71 children
      tested, 43 had high IgG levels of between two and half and five times the upper
      end of the normal age-matched reference range. While the same 43 children with
      high IgG had similarly elevated levels of IgM, only 25 of them had elevated IgA
      levels. Of this group of 43 children with hypergammaglobulinaemia, all but one,
      had antibodies to human immunodeficiency virus (HIV), 50% of whom had detectable
      levels of p24 antigen in their sera. A small minority, 4% of the 71 patients, had
      very low levels of total immunogloblins. CONCLUSIONS: High levels of total
      immunoglobulins occur frequently in children with pneumonia and are associated
      with the presence of HIV 1/2 antibodies and also p24 antigen.

PMID- 10892458
TI  - Migraine prevention--no longer a headache.

PMID- 10892457
TI  - Alcohol consumption in HIV-I infected persons: a study of immunological markers,
      Harare, Zimbabwe.
AB  - OBJECTIVE: To examine the effect of alcohol use in relation to the age, gender
      and plasma levels of HIV-I RNA and CD4 cells count in HIV-I infected persons as a
      prognostic indicator for the disease progression to AIDS. DESIGN: A community
      based cohort study. SETTING: The study was conducted at the Blair Research
      Institute Clinic from June 1996 to May 1998. SUBJECT: We interviewed 105
      volunteers, at a baseline and then followed them up on a three monthly basis.
      They underwent physical examinations and had blood drawn for laboratory tests.
      AUDIT Core was used to gain an indication of how much dependence there was on
      alcohol by patients in relation to demographic and immunological variables. MAIN
      OUTCOME MEASURES: Frequency of alcohol use and HIV-I disease progression to AIDS
      using viral loads and CD4 cells counts as measures of immune impairment. RESULTS:
      The volunteers had a mean (s d) age of 34.9 (7.3) years. Prevalence of alcohol
      use was 30.5% (n = 34.95% CI = 21.7 to 39.3). Most of the patients with CD4 cells
      count less than 200 mm3 did not use alcohol (p = 0.023) by the six months follow
      ups. There were no significant mean differences between users and nonusers of
      alcohol regarding the levels of both plasma viremia and CD4 cells count.
      CONCLUSION: Our finding is consistent with previous findings that found no
      relationship between alcohol use in persons with HIV-I infection and progression
      of disease to AIDS.

PMID- 10892459
TI  - Tuberculosis notifications in Australia, 1997. National TB Advisory Group.
      Communicable Disease Network Australia and New Zealand.
AB  - Since the inception of the National Mycobacterial Surveillance System (NMSS) in
      1991, annual crude notification rates for tuberculosis (TB) have remained stable
      at between 5 and 6 per 100,000 population. In 1997, there was a total of 1,001 TB
      notifications in Australia, of which 954 were new TB cases and 47 relapses. The
      corresponding annual crude notification rate for new and relapsed TB was 5.15 and
      0.25 per 100,000 respectively. Seventy-nine per cent of notifications that had a
      country of birth reported were overseas born. In keeping with trends observed
      over recent reporting years, the populations for which notified TB rates were
      highest include the overseas born from high prevalence countries and indigenous
      Australians. The lowest rates of disease have continued to be reported in the non
      indigenous, Australian born population. Surveillance reports over the last seven
      years indicate that the rate of disease in this population is gradually
      declining.

PMID- 10892461
TI  - Communicable Diseases Surveillance.

PMID- 10892460
TI  - Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance,
      1997. Report of the Australian Mycobacterium Reference Laboratory Network.
AB  - The Australian Mycobacterium Reference Laboratory Network collected and analysed
      laboratory data on new diagnoses of infection with Mycobacterium tuberculosis
      complex during 1997. A total of 722 cases were identified, representing an annual
      incidence of 3.9 cases of laboratory culture-confirmed tuberculosis (TB) per
      100,000 population. Historical data shows that Australia's TB incidence rates of
      culture-confirmed TB have varied little in recent years, ranging from 3.9 to 4.1
      cases per 100,000 population. The incidence rate continues to vary between
      States, reflecting differences in the distribution of persons belonging to high
      risk categories for TB. The male to female ratio showed a slight increase to
      almost 1.3:1, but in keeping with previous years, males with culture-confirmed TB
      were older (median age group 45-49 years) than females (median age group 35-39
      years), and approximately half of all pulmonary diagnoses involved positive
      microscopy. Lymphatic disease again accounted for almost 20% of the total cases,
      with 66% of cases being recorded in females. Approximately 9% of isolates, a
      decrease from 11% in 1996, had in vitro resistance to at least one of the four
      standard anti-tuberculosis drugs. Fourteen isolates were multi-drug resistant in
      1997 compared with 15 in 1996. Overall, the data indicates a remarkably stable
      picture for TB in Australia.

PMID- 10892462
TI  - Financing schools: analysis and recommendations.

PMID- 10892463
TI  - School finance: fifty years of expansion.
AB  - Since 1949-50, per-pupil expenditures in public elementary and secondary schools
      have more than quadrupled, even after adjusting for inflation. This article
      discusses some of the reasons. A significant share of the increase is the result
      of an 86% inflation-adjusted increase in teachers' salaries between 1949-50 and
      1971-72, although teachers' salaries have changed little in the following 25
      years. The ratio of students to school employees has dropped by half since 1949
      50 as a result of declining class sizes and the hiring of more nonteaching school
      employees, which significantly affects costs. Even maintaining class size at a
      constant level will cause school budgets to grow at a rate greater than that of
      inflation because schools must compete in a labor market against other employers
      who are able to produce more with fewer employees. A substantial part of the
      increase in per-pupil spending is a result of expansions in services provided by
      the schools. More expensive, specialized classes for high school students,
      compensatory education for students from disadvantaged backgrounds, special
      education and related services for students with disabilities, and desegregation
      efforts all contribute to higher costs. Efforts to improve funding equity have
      led to increased expenditures: rather than take funding from wealthier districts,
      most states prefer to raise the funding available to schools at the bottom and
      the middle of the scale, increasing total spending. Finally, a share of the total
      increase must be attributed to the workings of the political system governing
      schools.

PMID- 10892464
TI  - Sources of funding for schools.
AB  - Public school finance mechanisms differ from state to state, and they are often
      extremely complex. Most commonly, the federal government contributes about 7% of
      the total school budget, and the remainder is split fairly evenly between local
      contributions (primarily raised through local property taxes) and state
      contributions (primarily raised through state income taxes and sales taxes). The
      average amount of money provided per pupil varies greatly from one state to
      another. The method of distributing the state contribution to school districts is
      equally complex, often involving some combination of basic funding (which
      guarantees a minimum level of general purpose support per student), power
      equalization (which guarantees that a certain level of local taxation will yield
      a given level of per-pupil funding), local option (higher levels of taxation
      approved in some school districts, not equalized by the state), and categorical
      funding (supplemental state and federal funds, earmarked for specific needs such
      as special education or compensatory services to schools with a concentration of
      poverty, or to meet state-dictated priorities, such as reducing class size or
      purchasing state-approved textbooks). This complexity often leads to significant
      variation from district to district in the percentage of funding received from
      federal, state, and local sources and wide disparities in the level of support
      for the educational program. Typically, wealthier districts provide more of their
      funding from local taxes, while lower-income districts are more heavily dependent
      on state and federal sources.

PMID- 10892465
TI  - How and where the education dollar is spent.
AB  - Locally elected school boards have the authority and responsibility to decide how
      school budgets will be spent. In doing so, however, they must balance multiple
      funding restrictions and competing priorities. Despite great variance in local
      circumstances, most school districts have remarkably similar spending patterns,
      generally allocating from 60% to 63% of their budget to instruction and dividing
      the remainder among student services such as health services, counseling, and
      speech therapy; administration; building operation and maintenance; and food
      services and transportation. Polls show that many districts are attempting to
      delegate more decisions over resource allocation to the school site level.
      Research is just beginning to show what aspects of school site decision making
      are associated with improved teaching and learning.

PMID- 10892466
TI  - Equity and adequacy in school funding.
AB  - Since 1971, most states have been subject to lawsuits seeking to reform their
      education funding systems. These cases are litigated on the basis of state (not
      federal) constitutional language and generally seek either greater equity in
      funding among school districts or a guaranteed level of adequate funding for
      education. State supreme courts have found the finance systems unconstitutional
      in 16 states, and many states are still actively involved in litigation. Even
      where litigation has not occurred or has not succeeded, the prospect of
      litigation has prompted revisions of state funding policies. Despite the
      predominant role equity and adequacy play in litigation, there are no universally
      accepted definitions for either of these words in education funding. Most
      commonly, equity is measured in terms of the variation in per-pupil revenues
      among school districts in a single state. By this measure, some states have
      greater funding equity than others, and in most states wealthy districts have
      significantly higher per-pupil expenditures than do poor districts. Equity is
      likely to be greater when the residents of poor districts pay higher taxes. (In
      some states, residents in poorer areas pay twice as much of their income in local
      taxes as do residents of wealthier communities.) Equity is also greater in those
      states where the state's share of the education budget is higher and where the
      state consistently targets its contributions to lower-income districts. Much of
      current litigation and legislative activity in education funding seeks to assure
      "adequacy," that is, a sufficient level of funding to deliver an adequate
      education to every student in the state. Most states have not explicitly
      addressed the questions of how much education is "adequate" or how educational
      standards can be converted to a finance formula. Several approaches to
      calculating the cost of an adequate education are described.

PMID- 10892467
TI  - School finance policy and students' opportunities to learn: Kentucky's
      experience.
AB  - School finance reform is usually done piecemeal, with many changes made to an
      existing framework over a period of decades. Also, finance reform is generally
      carried out separately from reform of school programs or governance. A notable
      exception is Kentucky which, in response to a 1989 state supreme court ruling,
      created an entirely new elementary and secondary education system with new
      finance and governance mechanisms and new academic expectations and
      accountability mechanisms. This article summarizes the major elements of the
      Kentucky Education Reform Act (KERA) and research on its impact. Revenues
      increased, funding differences between districts shrank, but basic allocations
      (percentage spent on instruction, facilities, and so on) changed little. A new
      Office of Education Accountability, reporting to the legislature, tracks
      incentives and sanctions for schools that progress or regress against their
      baseline performance. School site councils (SSCs) are in operation, with
      authority to hire the principal and to make decisions about curriculum,
      instruction, and the school budget. Major instructional changes were implemented
      in the early elementary grades, and model restructured high schools are being
      studied. Significant supplemental services (both academic and social) have been
      added. Overall, much progress has been made in putting new structures in place,
      though changes in practice evolve more slowly. The article identifies barriers to
      change and concludes that KERA's strategy is promising, but more focus should be
      placed on school-level uses of education dollars. SSCs have authority, but they
      should also be offered substantial guidance regarding which practices will most
      reliably promote learning.

PMID- 10892468
TI  - Considering nontraditional alternatives: charters, private contracts, and
      vouchers.
AB  - Charter schools, vouchers, and contracts with private agencies providing
      educational services all reflect the belief that a substantial part of
      educational budgeting, decision making, and accountability should be based at the
      level of individual schools, rather than at the school district level. Though
      states are moving quickly to set up charter schools, and some states and
      districts are debating the merits of vouchers or experimenting with private
      contracts, in fact there is little information about the educational
      effectiveness of these innovations. Charter schools face substantial challenges
      in financing and business operations; many state charter school laws provide no
      start-up or capital funds and only limited operational funds. In addition, many
      charter school laws are vague on key questions of authority and school-district
      relations. Contracting with private agencies presents a wide range of options,
      many of which have been tried in only a few locations. The most publicized
      contracts with private agencies to run multiple schools have included some highly
      visible disappointments and no clear successes as yet, though experience is too
      limited to draw conclusions about contracting in general. Vouchers that may be
      used at private schools are extremely controversial for several reasons. Because
      private schools can decide which students they will accept, opponents are
      concerned that extensive use of vouchers may dramatically change the composition
      of the public school student body. It is also unclear whether vouchers to
      religious schools (which comprise 82% of all private schools in the United
      States) violate the constitutional requirement for separation of church and
      state.

PMID- 10892469
TI  - Class size.

PMID- 10892470
TI  - Tuition reimbursement for special education students.
AB  - The spring 1996 issue of The Future of Children on special education reviewed the
      legislative and litigation history of the Individuals with Disabilities Education
      Act (IDEA). This Revisiting article examines the impact of the two U.S. Supreme
      Court cases setting forth school districts' responsibility to reimburse parents
      of students with disabilities for private school tuition under certain
      circumstances. An extensive examination of published cases reveals that the
      number of cases litigated has increased but that the courts are no more likely to
      decide in favor of parents than they were before the Supreme Court rulings.

PMID- 10892471
TI  - School facilities.

PMID- 10892472
TI  - Equity considerations in funding urban schools.

PMID- 10892473
TI  - Catholic schools serving disadvantaged students.

PMID- 10892474
TI  - The future of children. A selected bibliography.

PMID- 10892475
TI  - Current and future trends in cataract surgery.

PMID- 10892476
TI  - Laser-assisted cataract surgery and other emerging technologies for cataract
      removal.
AB  - As we near the end of this century, refractive cataract surgery has become a
      reality through concerted contributions from ultrasonic phacoemulsification,
      foldable intraocular lens (IOL) implantation technology and keratorefractive
      surgery. As we enter the new millennium, our sights are set on realizing another
      dream: accommodative IOL surgery. Towards achieving this goal, many advances have
      been made in both techniques and technology of cataract removal. Lasers in
      particular have been under investigation for cataract removal for nearly two
      decades. The technology has now reached a stage where cataract can indeed be
      removed entirely with laser alone. Neodymium:YAG and erbium:YAG are the laser
      sources currently utilized by manufacturers of laser phaco systems. Initial
      clinical experience reported in the literature has served to highlight the
      capabilities of lasers and the need for further refinement. Despite the
      excitement associated with the availability of this alluring new technology for
      cataract removal, it is necessary to develop more effective laser systems and
      innovative surgical techniques that optimize its capabilities if laser phaco
      surgery is to be a genuine improvement over current techniques.

PMID- 10892477
TI  - pH-adjusted periocular anaesthesia for primary vitreoretinal surgery.
AB  - PURPOSE: To evaluate the efficacy of pH-adjusted bupivacaine in conjunction with
      medial orbital periconal block (periocular anaesthesia). METHODS: Sixty
      consecutive patients undergoing primary vitreoretinal surgery were enrolled
      prospectively. RESULTS: Adequate anaesthesia and akinesia with no intraoperative
      supplementation was achieved in 53 eyes (88.3%). Factors influencing
      intraoperative supplementation were combined vitrectomy with scleral buckling (p
      = 0.005) and duration of surgery of more than 2 hours (p = 0.001). No ocular or
      systemic complication resulted. CONCLUSION: pH-adjusted periocular anaesthesia is
      safe and effective in patients undergoing primary vitreoretinal surgery.

PMID- 10892478
TI  - Optic disc size in ocular hypertension.
AB  - PURPOSE: To study the optic disc size in eyes with ocular hypertension (OHT) in
      comparison to primary open-angle glaucoma (POAG) and normals. METHODS: Optic disc
      photographs obtained with the Nidek 3dx NM camera were digitized (Nikon coolscan)
      and disc area calculated using Littmann correction in a randomly chosen eye of 28
      OHT, 42 POAG and 30 normal subjects. OHT was defined as increased intraocular
      pressure with no disc or field changes suggestive of glaucoma with open angles.
      RESULTS: The optic disc area in OHT was 9.47 +/- 1.09 mm2; 12.27 +/- 2.87 mm2 in
      POAG; and 12.11 +/- 2.83 mm2 in normal individuals. CONCLUSION: Using
      magnification corrected morphometry and the criteria for OHT diagnosis, the optic
      disc area in OHT was significantly smaller (p < 0.0001) in POAG and normals.

PMID- 10892479
TI  - Visual outcome in optic nerve injury patients without initial light perception.
AB  - PURPOSE: To assess the prognosis for recovery of vision in patients with
      blindness due to head injury, and to analyse the predictive value of visual
      evoked potential (VEP). METHODS: One hundred consecutive patients with
      unilateral/bilateral blindness as a result of minor head injury were studied with
      regard to their visual status, CT scan, MRI scan and serial VEPs. Steroids were
      given to those presenting within one month of injury, 5 patients among them
      received methyl prednisolone. Transethmoidal decompression was done in 6
      patients. RESULTS: Visual improvement was recorded in 23 patients. Initial VEP
      failed to reveal any wave in 29 patients and was abnormal in 71. All the 14
      patients in whom VEPs were repeatedly normal, irrespective of initial VEP status,
      showed varying degrees of visual improvement and none of the 15 patients with
      persistently negative VEPs showed visual improvement. CONCLUSION: Recovery of VEP
      from no response to abnormal wave or abnormal wave to normal VEP were indicators
      of relatively good visual prognosis. Overall, 23 patients showed visual
      improvement, but did not return to normal. Mode of injury, CT findings and timing
      of surgery did not influence the outcome.

PMID- 10892480
TI  - Retained Viscoat and intraocular pressure after phaceomulsification.
AB  - PURPOSE: A single blind prospective randomised study to determine the effect of
      Viscoat retained in the eye on intraocular pressure (IOP) after
      phacoemulsification. METHODS: 82 patients were randomly selected to receive
      either Viscoat, a viscoelastic composed of 3% sodium hyaluronate (mol wt 500,000
      daltons), and 4% chondroitin sulfate (mol wt 25,000 daltons) or Provisc, a
      viscoelastic compound composed of 1% sodium hyaluronate (mol wt 4,00,000 daltons)
      during phacoemulsification. In those patients receiving Viscoat the viscoelastic
      in the anterior chamber only was removed, whereas in those receiving Provisc
      attempts were made to remove the material entirely. The IOP was measured on the
      first postoperative day, 16-20 hours after surgery. RESULTS: The mean
      postoperative IOP in the Viscoat group was 22.37 +/- 9.0 mmHg and in the Provisc
      group was 19.67 +/- 6.95 mmHg. Five patients in the Viscoat group had pressure
      elevations above 30 mmHg as opposed to three in the Provisc group. CONCLUSIONS:
      The two viscoelastics cause equivalent pressure elevations postoperatively. In
      the Viscoat group there were five patients with IOPs above 30 mmHg. We recommend
      that Viscoat should be aspirated from both the anterior chamber and the capsular
      bag following routine phacoemulsification.

PMID- 10892481
TI  - Laboratory investigations on viral and Chlamydia trachomatis infections of the
      eye: Sankara Nethralaya experiences.
AB  - PURPOSE: To review our experiences on the laboratory investigations of viral and
      chlamydial conjunctivitis, congenital cataract and acute retinal inflammations
      seen from 1990 to 1998 at Sankara Nethralaya, Chennai, India. METHODS:
      Conjunctival swabs/scrapings from 1061 patients with conjunctivitis were
      investigated. Nested polymerase chain reaction (nPCR) and restriction fragment
      length polymorphism (RFLP) techniques were applied on 74 conjunctival swabs
      during the 1996 outbreak of acute viral conjunctivitis. The occurrence of Rubella
      virus in 86 lens aspirates of congenital cataract was investigated. Tests were
      performed for the association of Herpes simplex virus (HSV), Varicella zoster
      virus (VZV) and Cytomegalovirus (CMV) with acute retinal inflammation in 32
      patients. RESULTS: The causative agents of conjunctivitis were Adenovirus in
      13.8%, HSV in 2.2% and C. trachomatis in 20.9% of the patients. Epidemics were
      due to Adenovirus type 4 in 1991, type 3 in 1992-93 and type 7a in 1996. PCR was
      37.9% more sensitive in detecting Adenovirus than virological methods. RFLP
      identified the conjunctivitis epidemic strain of 1996 as Adenovirus 7a. Rubella
      virus was isolated from 8.1% of lens aspirates from congenital cataract. Nineteen
      of the 32 patients with acute retinitis had confirmed virus infections (VZV: 8;
      HSV: 5; and CMV: 6) and the rapid detection of the virus agent helped institute
      specific chemotherapy resulting in useful vision in some patients. CONCLUSION:
      Laboratory investigations for diagnosis of viral and C. trachomatis ocular
      infections were useful in establishing the aetiology and determining the
      incidence of causative agents of specific ocular diseases.

PMID- 10892483
TI  - Bilateral simultaneous retinal vein occlusion.
AB  - Central retinal vein occlusion (CVO) is a common retinal vascular disorder with
      potentially blinding complications. However, a simultaneous bilateral affection
      is not a common entity. One such patient is described here.

PMID- 10892482
TI  - Bisected macula following retrobulbar steroid injection.
AB  - A case of bilateral accidental globe penetration during administration of
      retrobulbar steroid for bilateral optic neuritis is discussed. One eye with
      bisected macula was managed successfully by vitrectomy, internal gas tamponade,
      and postoperative laser to the edges of the retinal tear. The fellow eye was
      blind due to central retinal artery occlusion.

PMID- 10892484
TI  - Subacute sclerosing panencephalitis presenting as optic neuritis.
AB  - Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurologic
      disease affecting both grey and white matter of the brain in children and young
      adults. One such case which involved the visual system is described here.

PMID- 10892485
TI  - Intraocular gnathostomiasis.
AB  - We report a rare case of intraocular Gnathostomiasis, where a live worm,
      intracameral in location, was successfully removed. Its identity was confirmed by
      microscopy.

PMID- 10892486
TI  - Intravitreal tissue plasminogen activator in submacular haemorrhage.
AB  - Submacular haemorrhage is a major cause of sudden visual loss in age-related
      macular degeneration (AMD). If left untreated it often results in permanent
      central visual loss. We present our experience in the use of intravitreal tissue
      plasminogen activator (tPA) in a 65-year-old male with submacular haemorrhage.

PMID- 10892487
TI  - Malignant melanoma of ciliary body: a case report.
AB  - Ocular malignant melanomas are infrequently seen in Indian patents and most them
      involve the choroid. Ciliary body malignant melanoma is rather rare. This case
      report illustrates an occurrence in an Indian patient.

PMID- 10892488
TI  - Qualitative research in ophthalmic sciences.
AB  - Qualitative research was the preserve of social scientists before making inroads
      into medical sciences, as the medical fraternity was wedded to evidence-based
      medicine. Qualitative research methods are now being increasingly used in
      medicine. The goal of qualitative research is to help in the understanding of
      social phenomenon in their natural settings. These methods help to unravel
      mysteries relating to complex human interactions and to study the role of human
      behaviour in health and disease. Recent evidence points to the complementary
      roles of qualitative and quantitative methods in medical research. Qualitative
      methods include observations, interviews, focus groups, projective techniques,
      analysis of personal documents and accounts, sorting and ranking, and case
      studies. This communication describes the application of qualitative methods in
      ophthalmic research.

PMID- 10892489
TI  - Strategies for correcting surgical aphakia.

PMID- 10892490
TI  - Food as a vehicle of transmission of cholera.
AB  - Cholera has been recognized as a killer disease since earliest time. Since 1817,
      six pandemics have swept over the world, and the seventh one is in progress. The
      disease is caused by infection of the small intestine by Vibrio cholerae O1 and
      O139 and is characterized by massive acute diarrhoea, vomiting, and dehydration:
      death occurs in severe, untreated cases. Cholera is a highly contagious disease,
      and is transmitted primarily by ingestion of faecally-contaminated water by
      susceptible persons. Besides water, foods have also been recognized as an
      important vehicle for transmission of cholera. Foods are likely to be faecally
      contaminated during preparation, particularly by infected food handlers in an
      unhygienic environment. The physicochemical characteristics of foods that support
      survival and growth of V. cholerae O1 and O139 include high-moisture content,
      neutral or an alkaline pH, low temperature, high-organic content, and absence of
      other competing bacteria. Seafoods, including fish, shellfish, crabs, oysters and
      clams, have all been incriminated in cholera outbreaks in many countries,
      including the United States and Australia. Contaminated rice, millet gruel, and
      vegetables have also been implicated in several outbreaks. Other foods, including
      fruits (except sour fruits), poultry, meat, and dairy products, have the
      potential of transmitting cholera. To reduce the risk of food-borne transmission
      of cholera, it is recommended that foods should be prepared, served, and eaten in
      an hygienic environment, free from faecal contamination. Proper cooking, storing,
      and re-heating of foods before eating, and hand-washing with safe water before
      eating and after defaecation are important safety measures for preventing food
      borne transmission of cholera.

PMID- 10892491
TI  - A prediction model for moderate or severe dehydration in children with diarrhoea.
AB  - A hospital-based unmatched case-control study (387 cases and 387 controls) was
      carried out at the Government Medical College Hospital, Nagpur, India, to devise
      and validate a risk-scoring system for predicting the development of moderate or
      severe dehydration in children, aged less than five years, with acute watery
      diarrhoea. On unconditional multiple logistic regression, 12 risk factors-
      infancy, minority religion, undernutrition, not washing hands by mother before
      preparation of food, frequency of stools > 8/day, frequency of vomiting > 2/day,
      measles in previous 6 months, withdrawal of breast-feeding/other feedings,
      withdrawal of fluids during diarrhoea, not giving oral rehydration solutions
      (ORS), home available fluids and both during diarrhoea--were significant. Based
      on regression coefficients, these factors were ascribed statistical weights of 5,
      5, 4, 4, 22, 9, 11, 13, 5, 5, 5, and 7 respectively. The receiver-operating
      characteristic curve suggested a total score of 48 to be the best cut-off for
      predicting the development of moderate or severe dehydration. At this cut-off,
      the sensitivity, specificity, positive predictive value, Cohen's kappa, and
      overall predictive accuracy were 0.81, 0.81, 0.81, 0.61, and 0.86 respectively.
      If substantiated by further validation, this system can be used for predicting
      the development of dehydration at the earlier stage, thereby reducing the
      mortality associated with life-threatening dehydration.

PMID- 10892492
TI  - Outcome of children rehydrated in a hospital ORT corner in Bangladesh: a follow
      up study.
AB  - This prospective follow-up study was carried out during 1996 to identify the
      outcome of children rehydrated in the ORT Corner of the Chittagong Medical
      College Hospital. In total, 269 children, aged less than five years, who attended
      the ORT Corner, accompanied by their mothers, for treatment of uncomplicated
      acute watery diarrhoea with 'no signs of dehydration' and 'some dehydration,'
      were selected for the study. Mothers of the children were interviewed at the ORT
      Corner, and children were followed-up at home on the 5th post-ORT Corner visit
      day. The follow-up was completed for 260 cases (96.7%). At follow-up, 227 cases
      (87.3%) were found to be cured, and 33 cases (12.7%) still had diarrhoea. Of the
      cured, the mean duration of the episode was 5.84 +/- 2.34 days (95% CI.5.55-6.13
      days). All the cases received oral rehydration therapy (ORT) after attending the
      ORT Corner. Eighty-one cases (31.2%), however, reconsulted the private doctors.
      Of those who reconsulted, only 3 (3.7%) received WHO-recommended treatment of
      acute watery diarrhoea, and the rest 78 (96.3%) received medication. The
      medication prolonged the episode of diarrhoea significantly (6.22 days vs 5.48
      days, p < 0.001). None of the cases, who reconsulted the private doctors,
      revisited the ORT Corner. Treatment by 'ORS only' was mentioned by 64% of the
      mothers as the reason for non-revisit of the ORT Corner, and 20% of the mothers
      denied the receipt of any advice about when to revisit the ORT Corner which calls
      for further strengthening of communication activities of the ORT Corner.

PMID- 10892493
TI  - Analysis of human rotavirus G serotype in Bangladesh by enzyme-linked
      immunosorbent assay and polymerase chain reaction.
AB  - Distribution of human rotavirus G serotype was investigated by enzyme-linked
      immunosorbent assay (ELISA) and polymerase chain reaction (PCR) with faecal
      specimens obtained from children with diarrhoea in Bangladesh. By ELISA, subgroup
      and G serotype were determined for 59.5% and 28.6% of group A rotavirus-positive
      specimens respectively. However, of the 120 specimens, the G serotype of which
      was not determined by ELISA, serotype of the 112 specimens was typed by PCR. In
      total, G serotype was assigned for 95.2% of all the specimens, showing the
      highest rate of G4 (41.7%), followed by G1 (23.2%) and G2 (14.9%). Twenty-four
      specimens showed mixed types, such as G2 with G1, G8 or G9, or G1 with G4. These
      results indicate that PCR combined with ELISA is highly effective for G
      serotyping of rotavirus.

PMID- 10892494
TI  - Binding of Escherichia coli heat-stable toxin and rise of guanylyl cyclase
      activity in the brush-border membranes of rabbit intestinal epithelial cells.
AB  - The study examines the age-related differences in the density of Escherichia coli
      heat-stable enterotoxin (STa) receptors in the small intestine of rabbits. The
      number of STa receptors was found to be 1.7 x 10(12) in 14-day old rabbits
      compared to 2.4 x 10(9) in 14-week old rabbits per milligram brush-border
      membrane protein. The STa-induced guanylyl cyclase activity in the intestinal
      brush-border membranes was found to be stimulated by 6.2 folds over the basal
      enzyme activity in 14-day old rabbits, whereas in the 14-week old rabbits, it was
      4 folds over the basal activity. Moreover, the enzyme activity remained lower in
      the adult rabbits compared to the younger ones. Autoradiographic analysis of
      sodium dodecyl sulphate polyacrylamide gel electrophoresis showed two STa-binding
      proteins of apparent molecular weights of 140 and 38 kDa in the intestinal brush
      border membranes of rabbits.

PMID- 10892495
TI  - Combined infection of Norwalk-like virus and verotoxin-producing bacteria
      associated with a gastroenteritis outbreak.
AB  - Detection of multiple pathogens, particularly a combination of viruses and
      bacteria, is infrequently documented in outbreaks of gastroenteritis. This paper
      reports the presence of Norwalk-like virus (NLV) and enterohaemorrhagic verotoxin
      producing Escherichia coli in one individual, and NLV and verotoxin-producing
      Aeromonas sobria in another individual, both part of a large gastroenteritis
      outbreak. The causes of gastroenteritis in such outbreaks may be more complex
      than previously thought.

PMID- 10892496
TI  - Virulence patterns of Aeromonas eucrenophila isolated from water and infected
      fish.
AB  - Six isolates of Aeromonas eucrenophila--2 from water and 4 from superficial skin
      ulcer of cat fish--were examined for haemagglutination, serum sensitivity,
      chitinase production and enterotoxicity, and correlation, if any, between them;
      only one strain showed haemagglutination and was inhibited by both D-mannose and
      L-fucose. All the strains showed resistance to normal human serum, but produced
      chitinase; one of them elaborated inducible chitinase. All these strains caused
      fluid accumulation only after 1-4 serial passages through rabbit ileal loops, of
      which one strain that elaborated inducible chitinase caused significantly more (p
      < 0.005) fluid accumulation. These observations indicate that there is no
      correlation between enterotoxicity and haemagglutination and/or serum resistance,
      and these properties did not change after animal passage. However, a correlation
      could be observed between elaboration of inducible chitinase and enterotoxin
      production.

PMID- 10892497
TI  - Pigmented nails and Strongyloides stercoralis infestation causing clinical
      worsening in a patient treated for immunoproliferative small intestinal disease:
      two unusual observations.
AB  - Immunoproliferative small intestinal disease (IPSID) is commonly reported from
      developing countries with poor socioeconomic conditions, hygiene, and high
      frequency of gastrointestinal infections and infestations. The disease requires
      anti-malignant chemotherapy in lymphomatous stage. Reported here is a 20-year old
      man with IPSID lymphoma who responded to anti-malignant chemotherapy initially,
      but later deteriorated due to Strongyloides stercoralis infestation, which was
      treated successfully with mebendazole. Importance of an early recognition and
      adequate treatment for gastrointestinal infections and infestations before anti
      malignant chemotherapy for this disease is highlighted considering the occurrence
      of this disease in the developing world. The patient developed alternate brown
      black and white lines in the finger nails after combination chemotherapy, which
      has not been reported earlier in this disease; the nail changes disappeared 6
      months after the withdrawal of doxorubicin suggesting this drug as the cause for
      such nail changes during anti-malignant combination chemotherapy.

PMID- 10892498
TI  - Bibliography on diarrhoeal diseases.

PMID- 10892499
TI  - The antrochoanal polyp.
AB  - The different varieties of choanal polyps are reviewed by the authors according
      to their implantation pedicle. Their histology, possible pathogenesis, the
      various symptoms, steps in the diagnostic procedure and differential diagnoses
      are also described. Finally, the various modes of treatment are discussed,
      focussing in particular on the surgical methods and the new possibilities offered
      by developments in the field of endoscopy.

PMID- 10892500
TI  - Endoscopic endonasal surgery for paranasal sinus mucoceles.
AB  - Paranasal sinus mucoceles are benign, space-occupying, cystic lesions that
      require a surgical treatment. An endoscopic endonasal marsupialisation is
      nowadays the surgical approach of choice in most of the cases. The aim of the
      present study is to validate this option and to determine the clinical
      characteristics of paranasal sinus mucoceles. A retrospective study based on the
      clinical experience of several ENT surgeons was performed using a standardised
      questionnaire. The respondents participate to a report on endoscopic endonasal
      surgery for non-inflammatory disease in Belgium. One hundred and fourty patients
      presenting 178 mucoceles were included in this study. Primitive mucoceles were
      reported in 35% of the patients, posttraumatic mucoceles in 2.1% and
      postoperative mucoceles in 62.9%. The time interval between first rhinologic
      procedure and the mucocele diagnosis was respectively 24.4 months after FESS and
      108.3 months after an external procedure. Paranasal sinus mucoceles predominantly
      occur in the fronto-ethmoidal region (64%), followed by the maxillary sinus
      (18.6%), the sphenoid sinus (8.4%) and the posterior ethmoid sinus (6.7%).
      Uncommon locations were also reported in 2.3% (Inferior turbinate, middle
      turbinate, pterygomaxillary space). Endoscopic endonasal marsupialisation
      (combined with an external procedure for 8 patients) was successful in 97.9% of
      the patients. Only 3 patients showed recurrence. Endoscopic endonasal
      marsupialisation of paranasal sinus mucoceles is a reliable therapeutic option
      with favorable results and is supported by the questioned ENT surgeons in
      Belgium.

PMID- 10892501
TI  - EES in rare benign tumors.
AB  - Endoscopic Endonasal Surgery (EES) can successfully be carried out for benign
      tumors such as osteomas, benign vascular tumors, pituitary adenomas, pneumoceles
      and benign fibrous tumors. This report concerns a Belgian perspective documenting
      our experience in 49 such cases. Among them are 33 cases of pituitary adenoma.
      Thanks to the experience accumulated in the surgical management of inflammatory
      sinusal disease, these tumors were able to be removed, totally or partially,
      under endoscopic guidance with the aid of powered endoscopic instrumentation, and
      in some cases, CO2 laser fiber. Advantages are well-known; lower cost, shorter
      stay in hospital, lower morbidity, lower cosmetic or functional disabilities. We
      emphasize the need for the surgeon to be able to switch the endoscopic procedure
      to an external one if difficulties occur or the tumor is more extensive than
      expected.

PMID- 10892502
TI  - Pneumoceles of the paranasal sinuses (a case report).
AB  - We report a case of an infection of a large sphenoidal sinus communicating with a
      hyperaerated mastoid. Endoscopic drainage of this large cavity was successful. We
      suggest that EES should have a place in the treatment of the sinusal pneumocele.
      Surgery should however be reserved for cosmetic purposes, infection, algetic
      symptoms and ocular problems. A cosmetic correction with osteotomy and bone
      resection can be associated with the endoscopic surgery.

PMID- 10892503
TI  - Surgery of inverted papillomas under endoscopic control.
AB  - Six centers cooperated in a retrospective study on endoscopic surgical resection
      of Papillomas of the nose and paranasal sinuses in order to assess both the
      efficiency and the safety of this kind of surgical approach. From 1991 till march
      2000, 87 cases of Papillomas resections under--at least partially--endoscopic
      control were gathered, among which 85 were Inverted Papillomas (IP), 2 were
      Exophytic Papilloma (EP) and one was IP coexisting with Collumnar Cell Papilloma
      (CCP). Malignant transformation was found out in 3 cases of IP. Regarding the 85
      patients with IP demographics are as follows: 61 males, 24 females, with a mean
      age of 58.4 years (STDV: 13.96) in a range from 27 to 92 years. The mean follow
      up was of 41.9 months with range of 1-120 months. Fifteen recurrences occurred
      that were treated by revision surgery either under endoscopic control or by
      limited external approach. The mean time for recurrences to occur was 8.07 months
      with range of 1-24 months. The three patients with malignant transformation
      underwent postoperative radiation therapy. All of the patients are free of
      recurrence, however for some of them the follow-up is too short to definitely
      assess their free of disease status. The role of modern diagnostic tools in
      medical imaging--CAT and MRI--in order to assess clearly the limits of the tumors
      and to enhance the efficiency and the safety in the choice of a surgical approach
      is pointed out. The stress is put on the need for radical excision under
      endoscopic control which can be combined with the Caldwell-Luc transantral
      approach or with frontal trepanation for the cure of tumors impossible to be
      reached under endoscopic control only. Irrespective of the tumor extent and of
      the approaches that was used for excision a close endoscopic follow-up still
      remain mandatory, by trained surgeons, in the long term management of IP.
      Biopsies, CAT and/or MRI must be performed in any case with recurrence suspicion.

PMID- 10892504
TI  - Endoscopic endonasal ligation in treatment of severe posterior epistaxis.
AB  - The technique and indications of an endonasal endoscopic technique for treatment
      of posterior epistaxis are presented. Three cases were successfully treated in
      our department in 1999. The posterior vascularisation of the nose is reviewed
      with emphasis on surgical anatomy. Endoscopic endonasal ligation of posterior
      nasal arterial vascularisation is compared with other treatment choices in
      posterior epistaxis. The technique is save and efficient. Since it is also a
      minimally invasive technique, it has become our first choice surgical procedure
      for posterior epistaxis.

PMID- 10892505
TI  - Transcanalicular diode laser assisted dacryocystorhinostomy.
AB  - AIM OF THE STUDY: To assess the validity of transcanalicular diode laser assisted
      dacryocystorhinostomy (TLADCR) in the treatment of distal obstruction of the
      lachrymal pathways. MATERIAL AND METHOD: Between June 1999 and February 2000, 29
      TLADCR were performed in the ENT department on 26 patients. Surgical indications
      included chronic dacryocystitis in 19 cases and dacryostenosis in 10 cases. In
      all cases but one, the surgery was carried out under a standard general
      anesthetic. The diode laser was used with a power setting of 10 watts. RESULTS:
      Seventeen out of 29 TLADCR were regarded as having successful outcomes. 2 out of
      29 TLADCR had a little persisting tearing regarded as non debilitating and much
      less than which was present preoperatively. In 10 out of 29 TLADCR, the procedure
      was deemed a failure. These failures included 4 out of the 10 primary
      dacryostenosis and 6 out of the 19 chronic dacryocystitis. Two patients refused
      further treatment. In the other 8, surgical revision was undertaken via the
      traditional endonasal approach. In 7 of these cases, the lachrymal system was
      full of purulent secretions. COMPLICATIONS: Two patients developed a partial
      stenosis of one canaliculus that was diagnosed during the surgical revision.
      Another patient had a small fistula between the canalicular system and the skin
      of the corner of the eye that disappeared after the revision surgery. In one
      other case, the superior canaliculus was cauterised by the denudated portion of a
      resculpted laser fibre. Two bicanalicular nasal stent required reinsertion. Three
      patients developed a granuloma around the stent. Four patients developed an
      episode of infection whilst the stent was still in situ. CONCLUSION:
      Transcanalicular diode laser assisted dacryocystorhinostomy (TLADCR) performed
      with a 600-micron contact fibre is a relatively simple, elegant and effective
      procedure when used in conjunction with nasal endoscopy, to treat distal
      obstruction of the lachrymal pathways. But, the cost, the high prevalence of
      minor complications and the currently higher reported failure rate would favour
      external or endonasal approaches over this approach.

PMID- 10892506
TI  - Transnasal endoscopic orbital decompression and Graves' ophtalmopathy.
AB  - AIM OF THE STUDY: To assess the validity and the limits of endoscopic endonasal
      orbital decompression for Graves' ophtalmopathy resistant to the medical theapy.
      MATERIAL AND PATIENTS: Between September 1994 and May 1998, 16 patients with
      Graves' ophtalmopathy resistant to the medical treatment underwent an orbital
      decompression transnasally. 27 orbits were decompressed. The surgery was
      bilateral in 11 patients. In the 5 remaining cases, the surgery was unilateral.
      It was carried out on the left side in 2 cases and on the right side in 3 cases.
      RESULTS: Preoperatively, the average visual acuity was 8/10. Postoperatively, the
      visual acuity was 9.5/10. The average preoperative exophtalmometry measurement
      was 25.04 mm and the average postoperative measurement was 21.83 mm. The average
      retrodisplacement was 3.17 mm (range: 2-8). Preoperatively, 3 patients had mild
      diplopia whereas 5 others had moderate to severe extraocular muscle dysfunction.
      Postoperatively, 6 patients had mild diplopia whereas 10 patients required squint
      surgery for moderate to severe extraocular muscle dysfunction. CONCLUSION:
      Endoscopic orbital decompression improve all the symptoms of Graves'
      ophtalmopathy but one: the extraocular muscle dysfunction. Its cardinal
      indication is the treatment of compressive optic neuropathy whereas this surgical
      approach provides an excellent control of the medial wall of the orbit and the
      orbital apex. But the average reduction of proptosis of 3.17 mm is not high
      enough to propose this approach alone for the treatment of disfiguring proptosis.
      In such cases, a 2 or 3 wall orbital decompression should be performed to get
      marked cosmetic and functional improvement. In all cases, the patient should be
      informed about the risk of postoperative diplopia.

PMID- 10892507
TI  - Intranasal endoscopic surgery in traumatic optic neuropathy--the Belgian
      experience.
AB  - The management of traumatic optic neuropathy remains controversial. In this
      report we present the results of 8 patients treated by means of an intranasal
      endoscopic approach to the optic canal after at least 12 hours of corticosteroid
      therapy without improvement. Vision improved in four of the eight patients who
      underwent the surgery. There was no morbidity or mortality. As the results of the
      endoscopic optic nerve decompression are comparable to those reported using other
      surgical procedures, we feel that this approach merits consideration by surgeons.

PMID- 10892508
TI  - Endoscopic endonasal surgery (EES) in skull base repairs and CSF leakage.
AB  - This report aims to summarise the current role of Endoscopic Endonasal Surgery
      (EES) for skull base and cerebrospinal fluid (CSF) leakage repair, to provide
      some guidelines for the clinical diagnosis and technical procedures of repair, to
      demonstrate the limits of this approach and to discuss the Belgian experience of
      the recent years. Endoscopic surgery for chronic sinus disease is being performed
      with increasing frequency and CSF leak is an significant potential complication
      of this surgery, although the incidence of osteo-meningeal perforations in
      endonasal sinus surgery is below 1% overall. CSF leakage bears the risk of
      meningeal or intracranial infection and complication and therefore should be
      repaired as soon as recognised. Following proper localisation of the leak, repair
      is safely performed in most of the cases by endonasal route with the help of free
      mucoperiostal flaps taken from the inferior or middle turbinates. This also
      applies for lesions of other aetiologies. The Belgian data support the statement
      that the endonasal endoscopic approach is a suitable and successful technique to
      close CSF leaks in the vast majority of our patients.

PMID- 10892509
TI  - Endoscopic endonasal surgery in choanal atresia.
AB  - Twenty-seven cases of choanal atresia operated between 1979 and 2000 have been
      reported from 4 different institutions (19 females, 8 males, age of first
      surgical procedure ranging from 2 days to 35 years). Of these 27 cases, 22 were
      previously untreated. The outcomes for 19 of these new cases were available for
      the present report. Bilateral atresias were somewhat more frequent (15 versus 12)
      and associated anomalies were present in 10 out of 27 patients. Details about the
      types of atresia, associated anomalies, surgical techniques, duration of stenting
      and outcomes are given together with a theoretical review on choanal atresia.

PMID- 10892510
TI  - Endoscopic sinus surgery for juvenile nasopharyngeal angiofibroma.
AB  - Juvenile nasopharyngeal angiofibroma is a rare tumour of the head and neck with
      very specific characteristics: adolescent males, choana-nasopharynx,
      pterygomaxillary fossa widening, specific and intense vascularisation. Staging is
      very important in the decision of the surgical approach. Endoscopic management of
      juvenile nasopharyngeal angiofibroma is technically possible after preoperative
      embolisation. Up to now 13 angiofibroma have been treated using the endonasal
      endoscopic sinus surgery approach in Belgium (Leuven 8; Mont-Godinne 2; Ghent 1;
      Liege 1; Woluwe 1). In smaller tumors endoscopic resection has been successful in
      four cases without any recurrence. Five larger tumors, extending in the
      pterygomaxillary fossa, were also successfully resected. Extension into the
      infratemporal fossa or the cavernous sinus can be endoscopically removed, but
      recurrences may occur as they do after classical, external approaches. In
      conclusion, the endoscopic approach is an acceptable alternative in small to
      middle sized juvenile nasopharyngeal angiofibroma.

PMID- 10892511
TI  - Minimally invasive endoscopic management of malignant sinonasal tumours.
AB  - A large retrospective study from two belgian institutions of 78 patients who
      underwent minimally invasive endoscopic management for malignant sinonasal tumors
      from, 1992-1999 is presented. We attempt to assess the results of this less
      invasive approach. The spectrum of disease included adenocarcinoma, squamous cell
      carcinoma, olfactory neuroblastoma and other malignant tumors. All patients were
      treated primarily for cure. 66 patients were operated on by a purely endoscopic
      technique, while 9 patients had a simultaneous neurosurgical and endoscopic
      approach, and 3 a limited orbital approach. 16 patients (20.5%) presented with
      local recurrence, 6 patients (7.7%) sustained distant metastases and 7 patients
      (9%) presented simultaneous local recurrence and distant metastases. The 2-years
      and 5-years survival rates of the whole group were respectively 73.1% and 52.3%,
      while the adenocarcinoma group exhibits a significantly better prognosis than
      other histological types with 2-years and 5-years survival rates of 89.8% and
      63.8%. Patients who could be treated purely endoscopically had a significantly
      better survival in comparison to patients treated by an external and endoscopic
      approach. Morbidity was minimal and the local control rate as well as survival
      rates were comparable to literature data. Endoscopic resection was adequate,
      providing clear margins and en bloc removal in most cases. Our results encourage
      us to use this minimally invasive approach in selected cases as a reliable
      alternative to the systematic use of an exclusively external approach.

PMID- 10892512
TI  - Update on histamine as a mediator of inflammation.
AB  - Histamine is an important mediator and regulator of inflammation. Histamine acts
      via H1, H2, and H3 receptors that are functionally coupled to G-proteins and
      histamine release is regulated by cytokines that act as histamine release
      factors. Histamine suppresses the immune response and deviates the immune
      response toward the Th2 pathway.

PMID- 10892513
TI  - Antihistamines and epithelial cells.
AB  - Antihistamines have long been utilized in the symptomatic management
      (antihistaminic effects) of allergic rhinitis and conjunctivitis. Investigation
      into the nonsedating second-generation antihistamines suggests that they also
      possess antiinflammatory activity, and may be useful in the management of
      inflammation associated with allergic airway disease. In vitro studies have shown
      that these antihistamines decrease the migration and activation of eosinophils
      and diminish the release of pro-inflammatory mediators from mast cells and
      basophils after induction by immunological and nonimmunological stimuli. In vivo
      studies have also demonstrated that these antihistamines decrease inflammatory
      cell infiltration in allergic airway disease, and mediator release from mast
      cells and basophils. Epithelial cells, due to their spatial arrangement and
      predominance in the airways, play a pivotal role in the etiology of airway
      disease. There is evidence that antihistamines may modulate airway inflammation
      by influencing the activity of these airway epithelial cells. Studies have shown
      that expression of adhesion molecules on epithelial cells is decreased by second
      generation antihistamines. Collectively, these studies suggest that second
      generation H1-histamine receptor antagonists have potential use either as safe
      antiinflammatory alternatives to corticosteroids or as rescue medication in
      combination with corticosteroids for the management of severe airway disease.

PMID- 10892514
TI  - Molecular pharmacology of second-generation antihistamines.
AB  - Histamine was the first allergic mediator identified in the early part of this
      century. It has three defined receptors, but most effects of histamine in
      allergic reactions are through the H1 receptor. The first H1 antagonists were
      introduced into clinical use in the late 1940s, and drugs of this class are still
      the preferred initial choice for management of allergic rhinitis and urticaria.
      The first-generation drugs were characterized by nonspecific binding to many
      receptors and penetration of the blood-brain barrier, resulting in multiple side
      effects. Within the central nervous system (CNS), interference with normal
      histamine binding to the H1 receptor is associated with drowsiness and
      psychomotor impairment. The second-generation drugs have a much improved
      benefit/adverse effect profile, largely based on greater potency, receptor
      specificity, and lower CNS penetration. The potency of antihistamines for
      blocking H1 receptors can be compared by their inhibition of the cutaneous wheal
      and flare response to histamine. These drugs seem to have additional antiallergic
      properties related to blockade of mediator release and interference with cellular
      recruitment and activation. Clinical trials comparing the efficacy of
      antihistamines in rhinitis and asthma are reviewed. Recent studies have explored
      the potential of antihistamines to prevent the progression of allergy and their
      enhanced efficacy when combined with leukotriene antagonists.

PMID- 10892515
TI  - Idiopathic anaphylaxis: variants as diagnostic and therapeutic problems.
AB  - Idiopathic anaphylaxis presents a problem requiring rapid diagnosis and
      initiation of therapy. Some cases are complex and difficult to assess. We present
      four cases of unusual complexity to illustrate diagnostic and therapeutic
      problems. Two cases were found not to be idiopathic anaphylaxis, one being
      undifferentiated somatoform idiopathic anaphylaxis and the other very severe
      urticaria. Various conditions can be or mimic idiopathic anaphylaxis, and
      patience and observation can result in reasonable outcomes.

PMID- 10892516
TI  - Nitric oxide production and apoptosis by GP120.
AB  - Nitric oxide (NO) is increased by gp120 in astrocytes and in monocyte-derived
      macrophages. Of the gp120 fragments (F1: amino acid 254-274, F2: amino acid 315
      329, F3: amino acid 421-438), F1 has been shown to increase NO in astrocytes and
      gp120 also primes CD4+ T cells for apoptosis. Peripheral blood mononuclear cells
      (PBMCs) at 10(6)/ml (N = 10) were incubated at 24 and 72 hours in RPMI, 10% CO2
      with low doses (100 nM) gp120 and high doses (400 nM) of the smaller fragments.
      Supernatants were collected and assayed for the relative contribution of gp120
      and its fragments on NO production at both time points. Apoptosis was detected by
      in situ hybridization with and without 1 microgram/ml LPS as superantigen at 72
      hours. The major contribution to apoptosis and NO production was from F1. At 24
      hours F1 had a 1.9-fold increase from control, whereas F2 and F3 had 1.25- and
      1.35-fold increases. At 72 hours both F1 and F2 had a 1.5-fold increase and F3
      had a 1.33 increase. Thus, F1 contributed significantly to NO production at 24
      hours. Both F1 and F2 had significant contributions to NO production at 72 hours.
      F1 had the most contribution to apoptosis both with and without
      lipopolysaccharide (LPS). These findings may contribute to further understanding
      the mechanism of HIV-induced apoptosis.

PMID- 10892517
TI  - Impact of changes in asthma severity on health-related quality of life in
      pediatric and adult asthma patients: results from the asthma outcomes monitoring
      system.
AB  - The goals of asthma treatment have broadened beyond managing traditional clinical
      markers of disease severity, and now include a focus on benefits of treatment in
      terms that are most meaningful to patients. Measurement of both generic and
      disease-specific health-related quality of life (HQL) is advocated because each
      provides complementary information about how the condition affects everyday
      functioning and well-being and whether treatments have their intended effects.
      The purpose of this study was to determine the impact of changes in asthma
      severity (defined using NHLBI/NAEPP severity staging) on patient-assessed HQL.
      Two hundred and thirty-three pediatric asthma patients and 269 adult asthma
      patients were evaluated in a one-year observational study. Analyses were
      performed to compare the generic and asthma-specific scores for patients whose
      asthma severity improved, stayed the same, or worsened over one year. The asthma
      specific scales are sensitive to changes in disease severity. Of the generic
      scales, those tapping areas of physical health are more affected than the
      mental/emotional scales. This confirms that HQL measures are responsive to
      changes in asthma severity. They complement traditional clinical markers used to
      evaluate changes in a patient's disease state and thus give the physician another
      useful tool in following the clinical progress of the child with asthma.

PMID- 10892518
TI  - Allergen immunotherapy: guidelines, update, and recommendations of the World
      Health Organization.
AB  - Allergen immunotherapy (AIT) is the administration of increasing doses of an
      allergen vaccine to an allergic subject in order to reach a dose effective to
      improve symptoms associated with subsequent exposure to the causative allergen.
      This form of therapy is effective in the treatment of allergic
      rhinitis/conjunctivitis, allergic reactions to stinging insects, and allergic
      asthma. It is the only therapeutic modality that can affect the natural course of
      allergic diseases, and may prevent the development of asthma in patients with
      allergic rhinitis. AIT is indicated for patients with demonstrated specific IgE
      antibodies against clinically relevant allergens. The mixture of allergens to be
      utilized is based on the patient's history and skin and laboratory tests. The
      major risk of AIT is anaphylaxis. Such therapy is continued for three to five
      years, but the decision to discontinue it should be individualized.
      Interpretation of the history, physical findings, and skin and laboratory tests,
      the prescription and administration of allergen immunotherapy, its integration
      into the patient's treatment plan, and the decision to discontinue it require
      qualifying experience provided by specialist training in allergy and immunology.

PMID- 10892519
TI  - Comment to the paper "eosinophil active cytokines and surface analysis of
      eosinophils in Churg-Strauss syndrome" (Jan.-Feb., 1999).

PMID- 10892520
TI  - Antihistamines and managed care: old versus the new.

PMID- 10892521
TI  - From immunity to autoimmune disease, a historic trail. Part III.

PMID- 10892522
TI  - Asthma among the famous. Dylan Thomas (1914-1953) Welsh poet and author.

PMID- 10892523
TI  - Physiologic and related behavioral outcomes from the Women's Lifestyle Heart
      Trial.
AB  - The Women's Lifestyle Heart Trial was a small (N = 28) randomized controlled
      trial to evaluate the effects of a comprehensive lifestyle self-management
      program (very low-fat vegetarian diet, stress-management training, exercise,
      group support, and smoking cessation) on reduction of cardiovascular risk factors
      in postmenopausal women with coronary heart disease (CHD). Women assigned to the
      treatment condition (Prime Time) participated in a week-long retreat followed by
      twice-weekly 4-hour meetings. Endpoints were program adherence; changes in lipid
      profiles, body mass, blood pressure, hypolipidemic and antihypertensive
      medications; and quality of life. Risk factor and psychosocial evaluations were
      conducted at baseline and at 4, 12, and 24 months. Repeated measures analyses of
      covariance revealed that the dietary, stress management, and physical activity
      changes made by intervention women were dramatic and lasting. There were
      significantly greater improvements in the Prime Time condition compared to the
      usual care control group on body mass, angina symptoms, and quality of life, and
      a tendency for a greater reduction in blood pressure-lowering medications.
      Similar patterns were seen in lipids, blood pressure, and lipid-lowering
      medications, but did not reach significance. These results demonstrate that
      postmenopausal CHD women can make lasting lifestyle changes, and that these
      changes may reduce the need for cardiac medications and improve CHD risk factors
      and quality of life.

PMID- 10892524
TI  - Age comparisons in acquiring biofeedback control and success in reducing headache
      pain.
AB  - This article presents a review and archival analysis to assess age differences in
      acquiring biofeedback control and success in treating recurrent headache by using
      data from 56 studies with either adult (total N = 503) or child (total N = 98)
      subjects. All studies focused on treating headache with temperature biofeedback
      (TBF) or electromyographic (EMG) biofeedback. To standardize the varied measures
      across studies, we calculated each study's percent change scores for biofeedback
      performance and headache activity. All headache activity scores included
      assessments of pain intensity. We then calculated subject-weighted means of
      percent change for biofeedback performance and for headache activity by summing
      the products of each relevant percent change score and N and then dividing by the
      total number of subjects contributing to those sums. Results showed that both
      children and adults reported substantial improvements in headache activity with
      TBF and EMG biofeedback treatment (Ms ranged from 34% to 81%), but children
      showed significantly greater improvement than adults. No age differences were
      found in the acquisition of biofeedback control. Further analyses revealed two
      additional findings. First, biofeedback control and headache improvement were
      strongly correlated. Second, headache activity continued to decrease in the weeks
      following treatment, and this decrease was significantly greater for children
      than adults.

PMID- 10892525
TI  - Stress and metabolic control in diabetes mellitus: methodological issues and an
      illustrative analysis.
AB  - RATIONALE: The purpose of this article was twofold: a) to review studies of
      stress and glycemic control in diabetes, and b) to present a data analysis that
      illustrates the complexities of investigating stress in relation to blood
      glucose. The literature review emphasized human studies and the strengths and
      weaknesses of alternative designs. Special consideration was given to
      longitudinal investigations, and an analysis of data from the Diabetes Control
      and Complications Trial (DCCT) was presented to exemplify this approach. Nine
      individuals with Type 1 diabetes who participated in this project at the
      University of Iowa were studied over a period of 2 years. Stress was multiply
      measured (Life Experiences Survey, Hassles Scale, Perceived Stress Scale) as was
      blood glucose control (daily reflectance meter readings; monthly HbA1c). Within
      subject time-series analyses and a combined longitudinal/cross-sectional model
      were used to analyze data. Two of the nine subjects manifested significant
      correlations between stress and HbA1c, and six subjects exhibited significant
      associations between stress and daily level or variability of glucose readings.
      The latter correlations varied in sign and appeared to cluster around specific
      individuals rather than a particular measure of stress or blood glucose.
      CONCLUSION: While the subjects may not represent the full spectrum of individuals
      with Type 1 diabetes, results were consistent with earlier longitudinal research
      in suggesting that the strength and direction of the relationship between stress
      and blood glucose control varies considerably between individuals.

PMID- 10892526
TI  - Cognitive-behavioral stress management reduces distress and 24-hour urinary free
      cortisol output among symptomatic HIV-infected gay men.
AB  - BACKGROUND: Stress management interventions can reduce symptoms of distress as
      well as modulate certain immune system components in persons infected with human
      immunodeficiency virus (HIV). These effects may occur in parallel with reductions
      in hypothalamic-pituitary-adrenal (HPA) axis hormones such as cortisol, which has
      been related in other work to a down-regulation of immune system components
      relevant to HIV infection. The present study tested the effects of a multimodal
      cognitive-behavioral stress management (CBSM) intervention on 24-hour urinary
      free cortisol levels and distressed mood in symptomatic HIV+ gay men. METHODS:
      Symptomatic HIV-infected gay men who were randomized to either a 10-week group
      based CBSM intervention or a 10-week wait-list period provided psychological
      responses and urine samples pre-post intervention. RESULTS: Of the 59
      participants providing matched questionnaire data, men assigned to CBSM (n = 40)
      showed significantly lower posttreatment levels of self-reported depressed
      affect, anxiety, anger, and confusion than those in the wait-list control group
      (n = 19). Among the 47 men providing urine samples (34 CBSM, 13 controls), those
      assigned to CBSM revealed significantly less cortisol output as compared to
      controls. At the individual level, depressed mood decreases paralleled cortisol
      reductions over this period across the entire sample. CONCLUSION: A time-limited
      CBSM intervention reduced distress symptoms and urinary free cortisol output in
      symptomatic HIV+ gay men and greater reductions in some aspects of distress,
      especially depressed mood, paralleled greater decreases in cortisol over the
      intervention period. If persisting stressors and depressed mood contribute to
      chronic HPA axis activation in HIV-infected persons, then interventions such as
      CBSM, which teaches them to relax, alter cognitive appraisals, use new coping
      strategies, and access social support resources, may decrease distress and
      depressed mood and normalize HPA axis functioning.

PMID- 10892527
TI  - Health behavior changes after a cancer diagnosis: what do we know and where do we
      go from here?
AB  - Survival rates for certain types of cancer have improved over the past few
      decades. Changing unhealthy behaviors such as smoking, poor diet, and sedentary
      life-style among individuals who have been diagnosed with cancer may help to
      reduce cancer treatment sequelae, possibly reduce risk of recurrence for specific
      types of cancer, and reduce risk for other common diseases such as cardiovascular
      disease, obesity, and hypertension. This article reports the prevalence of each
      of these behaviors among those diagnosed with cancer and reviews interventions
      that have targeted these risk behaviors. There is considerable variation in the
      type of research questions asked, the methodologic quality of the research,
      sample sizes, and the outcomes observed across studies focusing on changing the
      three health risk behaviors. In the final section, we provide guidelines for
      researchers in developing health behavior interventions for individuals diagnosed
      with cancer and highlight challenges that should be addressed.

PMID- 10892528
TI  - Looking forward and back: distress among women at familial risk for breast
      cancer.
AB  - Healthy women with family histories of breast cancer in a first-degree relative
      (FH+) have been reported to exhibit higher levels of breast cancer-related
      distress than women without family histories of breast cancer (FH-). Recent data
      suggest that this may be particularly true for women who had a parent die of
      cancer. In line with theories emphasizing the psychological impacts of past
      stressors and concerns for the future, the present study examined the hypotheses
      that past cancer stressors (i.e. maternal breast cancer caregiving and death,
      "Looking Back") and perceptions of one's own heightened future risk for
      developing the disease ("Looking Forward") would predict current levels of
      distress. One hundred forty-eight healthy women (57 FH+, 91 FH-) recruited from
      large medical centers in the New York City area completed measures of breast
      cancer-related distress, general psychological distress, and items assessing
      whether or not they had taken care of their mother with breast cancer or had had
      their mother die from the disease. Consistent with previous research, results
      indicated that FH+ women whose mothers had died of breast cancer had
      significantly higher breast cancer-related distress than either FH+ women whose
      mothers had not died of breast cancer or FH- women (p < .05). Further analyses
      revealed that FH+ women who had cared for their mothers with breast cancer had
      higher cancer-related distress than women who did not (p < .01), and that FH+
      women whose experience included both caregiving and the death of their mother
      from breast cancer had the highest levels of cancer-related distress (p < .01)
      and depressive symptoms (p < .05). Findings also indicated that FH+ women with
      heightened perceptions of risk for breast cancer had higher levels of distress,
      independent of past stressors. These findings suggest that psychosocial
      interventions for women with family histories of breast cancer might be
      appropriately focused on these issues.

PMID- 10892529
TI  - Anger expression, gender, and ambulatory blood pressure in mild, unmedicated
      adults with hypertension.
AB  - The suppression of anger has been associated with the development of
      hypertension. This study evaluated the association between anger management style
      (anger-in and anger-out) and ambulatory blood pressure (ABP) in patients with
      repeated clinic diastolic blood pressures (DBPs) between 90-105 mmHg, unmedicated
      and with no known coronary artery disease. A total of 128 men (46.0 years) and 66
      women (46.6 years) participated. Fourteen percent of men and 35% of women were
      classified as having "white coat" hypertension (daytime DBP < 85 mmHg). Mean
      awake and sleep DBP and systolic blood pressure (SBP) were evaluated in a
      repeated measures analysis of variance (ANOVA). Anger-in and anger-out scores
      were categorized into low, medium, and high t-scores (< 50, 50-59, > or = 60).
      Results indicated that in women, increasing anger-in is associated with greater
      SBPs while awake and sleeping, whereas no effect was found for DBP, nor any
      effect in men. No significant association was found between gender, anger-out,
      and ABP. The clinical diagnostic status of white coat hypertension was not
      differentially associated with anger-in or anger-out in men and women. In
      conclusion, in a sample of mild unmedicated adults with hypertension, suppression
      of anger is associated with greater ambulatory SBP in women, but not in men.

PMID- 10892530
TI  - Perceived stress and blood pressure in early adolescent children.
AB  - The objective of this investigation was to determine the individual contributions
      of perceived daily, major, and total stressors to blood pressure in early
      adolescent children. Toward this goal, cardiovascular risk factors were assessed
      in 74 6th-grade students. Height and body weight, measured in standard fashion,
      were used to calculate body mass index (BMI). Waist and hip circumferences and
      triceps and calf skinfolds were taken to determine the distribution and
      percentage of body fat, respectively. Seated resting blood pressure was obtained
      using a mercury sphygmomanometer. The dietary sodium-to-potassium ratio was
      calculated from a food intake questionnaire. Family history of hypertension was
      self-reported by participant's parents, and physical activity and perceived
      stress levels were determined by questionnaire. When added to the hierarchical
      regression models, the perceived stress variables did not significantly predict
      any additional variance in systolic or diastolic blood pressure in this early
      adolescent sample. Additionally, bivariate correlations between the stress
      variables and blood pressure were nonsignificant. The nonpsychological
      hypertension risk factors accounted for 25%-35% of the total variance in systolic
      and diastolic blood pressure. Further, regression analyses revealed that with the
      exception of BMI and the sodium-to-potassium ratio, no other risk factors were
      independent predictors of systolic or diastolic blood pressure. Further
      identification and understanding of environmental precursors of childhood
      hypertension is recommended.

PMID- 10892531
TI  - A preliminary study of breast-feeding and maternal symptomatology.
AB  - The association between breast-feeding status and maternal health is examined. A
      survey questionnaire was presented via the World Wide Web. Self-reports of 168
      breast-feeding and 65 weaned mothers between 4 and 208 weeks postpartum were
      compared for physician visits, symptomatology, and Perceived Stress Scale scores
      in the last month. Breast-feeding was associated with fewer physician visits and
      symptoms and less perceived stress. Moreover, the longer a woman breast-fed
      before she weaned, the fewer the symptoms and less stress she reported. Breast
      feeding is associated with better maternal health both during the breast-feeding
      period and after weaning. Further research on the effects on maternal health of
      breast-feeding is indicated. Future prospective longitudinal investigations
      should address the possible inhibition of lactation by stress and physiological
      mechanisms that may link breast-feeding and weaning with maternal health.

PMID- 10892532
TI  - Underutilizers of mammography screening today: characteristics of women planning,
      undecided about, and not planning a mammogram.
AB  - Using concepts from the Precaution Adoption Process Model, we identified
      behavioral factors, sociodemographic and psychosocial variables, and beliefs
      about breast cancer that discriminated among women at different stages with
      regard to their intention to obtain mammography screening. An independent survey
      company conducted telephone interviews with 2,507 women aged 50 to 80 who were
      identified as underutilizers of mammography screening. Each underutilizer was
      assigned to one of three stages with regard to intention to get a mammogram: (a)
      definitely planning, (b) thinking about, and (c) not planning. Estimated actual
      risk of breast cancer, perceived risk to breast cancer, worry about breast
      cancer, and fear of learning from a mammogram that one has breast cancer were
      variables found to be significantly associated with intention to obtain a
      mammogram for several subgroups of underutilizing women. There are significant
      behavioral and psychosocial variables, beliefs and feelings about breast cancer,
      and demographic characteristics that distinguish underutilizing women at various
      stages with regard to intention to obtain mammography screening. Our findings
      provide new information that could help the health care professional motivate
      women who are not planning to utilize this preventive health measure to become
      regular utilizers.

PMID- 10892533
TI  - Using direct mail to recruit Hispanic adults into a dietary intervention: an
      experimental study.
AB  - Identifying strategies for successful recruitment of ethnic minorities into
      scientific studies is critical. Without effective methods, investigators may fail
      to recruit the desired sample size, take longer to recruit than planned, and
      delay progress for research in minority health. Direct mail is an appealing
      recruitment method because of the potential for reaching large target populations
      and producing a high volume of inquiries about a study with relatively little
      staff effort. To determine which of three direct mail strategies yielded higher
      recruitment, 561 Hispanic employees were randomly assigned to receive either: (a)
      a flyer about a worksite dietary intervention; (b) the same flyer plus a
      personalized hand-signed letter containing heart disease risk statistics for the
      general American population; or (c) the flyer plus a personalized hand-signed
      letter containing statistics for Hispanics. Two orthogonal chi-square comparisons
      were examined. The personalized letters plus flyer yielded a significantly higher
      response rate (7.8%) than the flyer alone (2.1%), X2(1, N = 561) = 7.5, p = .006.
      However, the personalized letter with Hispanic heart disease risk statistics did
      not yield a statistically significant higher response rate (9.1%) than the letter
      with the general population risk statistics (6.5%), X2(1, N = 370) = 0.9, p >
      .34. These findings suggest that personalized approaches can increase the
      effectiveness of direct mail efforts for recruiting ethnic minorities into
      interventions and may be particularly helpful for large-scale interventions.

PMID- 10892534
TI  - Results of a volunteer program to conduct dietary intervention research for
      women.
AB  - The American Cancer Society (ACS) initiated the Breast Cancer Dietary
      Intervention Project (BCDIP) to involve community volunteers in cancer-related
      intervention research activities focused on dietary fat reduction in women with
      breast cancer. This article presents data on the volunteer aspects of the
      project, with two aims: (a) to describe the volunteer recruitment and
      intervention designed for the BCDIP, conducted jointly by the American Cancer
      Society and the Fred Hutchinson Cancer Research Center, and (b) to present
      baseline characteristics and predictors of retention of the BCDIP volunteers.
      There were five types of volunteers, called volunteer adjunct researchers or
      VARs, in the BCDIP. VARs were recruited using a variety of approaches, including
      electronic media alerts, flyers in oncology clinics, and notices in the
      newsletters of state nursing and nutritional professional organizations. Over
      half of all VARs came from two main sources: the media (television, radio,
      newspapers) and from work-related sources. Over half (58%) of the VARs had
      professional licenses in nursing or dietetics, and 46% were employed full-time.
      Several types of motivations for participating in the BCDIP, including altruistic
      reasons (want to help others, help people with cancer), health concerns
      (family/friend with breast cancer, have had cancer), and work-related reasons
      (gain professional skills) were important. Sixty-eight percent of VARs remained
      with the project for its entirety. Predictors of retention in the VAR program
      included previous ACS volunteer experience with initial motivations to volunteer
      and the interaction of employment status and professional nursing training. In
      future research and community-based projects, better recruitment and volunteer
      coordination procedures should be used to reduce dropout rates and maintain
      volunteer commitment and participation.

PMID- 10892535
TI  - Advocacy in perioperative nursing practice.
AB  - Advocacy describes the act of pleading for, supporting, and active espousal. It
      implies taking action to achieve a goal on behalf of oneself or another. In
      nursing, the patient's wishes often serve as the impetus for advocacy.
      Perioperative nurses function as advocates and accept responsibility to safe
      guard the rights of surgical patients. This article describes historical aspects
      of and conceptual problems in nursing advocacy, and it presents case studies that
      demonstrate advocacy by the perioperative nurse.

PMID- 10892536
TI  - Treating glaucoma with drainage devices and pericardial grafts.
AB  - Glaucoma is caused by a sustained elevation of intraocular pressure due to the
      decreased drainage of aqueous humor from the anterior chamber of the eye. There
      are many types of glaucoma, which, if left untreated, may have devastating
      results for the patient. Glaucoma can remain uncontrolled after medical and
      surgical interventions. Glaucoma drainage device implants with pericardial graft
      placements often are helpful in relieving the effects of glaucoma and increasing
      the patient's quality of life.

PMID- 10892537
TI  - New nurse-to-patient ratio legislation and its effect on perioperative nursing.

PMID- 10892538
TI  - Collecting, analyzing, and interpreting focus group data.
AB  - Conducting a focus group is only one approach to gathering information. The
      worthiness of the information derived from a focus group depends on many factors.
      The main advantage of a focus group is that it is a convenient, cost-effective,
      relatively fast method to collect information from a number of individuals.
      Useful information only can be obtained with special attention to research
      methods and assessment of the reliability and validity of collected data. Using a
      focus group should be considered when the method is appropriate to answer the
      research question. Remember, adequate resources and skill are required to conduct
      a focus group in a manner that ensures the quality of the results.

PMID- 10892539
TI  - Short cut of protein purification by integration of cell-disrupture and affinity
      extraction.
AB  - Screening strategies based on functional genomics require the isolation of gene
      products of several hundred cDNA clones in a fast and versatile manner.
      Conventional purification strategies will fail to accomplish this goal within a
      reasonable time frame. In order to short-cut these procedures, we have developed
      a combination of cell disintegration and affinity technique for rapid isolation
      and purification. For our purpose, tagged proteins have been produced in yeast by
      fusing the FLAG-sequence adjacent to the 5' end of cDNAs coding for the
      respective protein. The example of an over-expressed FLAG-tagged fusion protein,
      human serum albumin (HSA), was released into the cytoplasm. Detection and
      purification of the FLAG-fusion protein were carried out by using a mouse
      monoclonal antibody directed against the FLAG-peptide. For purification purposes,
      the antibody was immobilized on PROSEP magnetic glass beads. These magnetic glass
      beads with 500 microns diameter have been investigated for disintegration of
      yeast and simultaneous capturing of the target protein. After 60 s, 90% of the
      maximal disintegration level was achieved when a ratio of 20 microliters yeast
      cell suspension and 100 microliters glass are vortexed. After a wash step, the
      FLAG-fusion proteins have been eluted with chelating agents such as EDTA. The
      short-cut procedure has been compared to a conventional purification strategy
      using an affinity chromatography process. Due to the highly favorable binding
      characteristics of the applied immunoaffinity sorbent the yield observed in batch
      operation was 90% and purity in the range of 70-80%.

PMID- 10892540
TI  - Peptide fusion tags with tryptophan and charged residues for control of protein
      partitioning in PEG-potassium phosphate aqueous two-phase systems.
AB  - A partition study with peptides and recombinant proteins in poly(ethylene
      glycol)4000-potassium phosphate aqueous two-phase systems has been performed. The
      aim was to study to what extent the insertion of charged residues could affect
      protein partition in addition to the already observed effects of tryptophan
      residues. The model proteins used are based on a staphylococcal protein A
      derivative, Z, and modified by the insertion of peptide tags close to the C
      terminus. The tags differed with respect to their content of both Trp, negatively
      (Asp) and positively charged (Lys) amino acid residues. The same partitioning
      trends were observed for the peptides and fusion proteins. The effect of Trp
      residues was to direct the partitioning towards the PEG phase. The insertion of
      two negatively charged (Asp) residues into a Trp4-tag enhanced the partition
      towards the PEG phase even more. The introduction of positively charged (Lys)
      residues in addition to Trp residues, on the other hand, pulled the peptide or
      protein towards the potassium phosphate phase. The partitioning of peptides gave
      a good qualitative picture of the effect of the peptide on partitioning when
      fused to the protein. The efficiencies of the tags were calculated based on
      partitioning of tags and fusion proteins, and tag efficiencies generally varied
      between 60 and 85%.

PMID- 10892541
TI  - The effect of demulsifiers on lysozyme extraction from hen egg white using
      reverse micelles.
AB  - The liquid-liquid extraction of protein from buffered aqueous phases using
      reverse micelles (RM) has been extensively researched from a fundamental point of
      view. However, very little effort has been expended at scaling up this process
      for the extraction of real fermentation broth. When real broths are used with
      reverse micellar phases there are major problems with emulsion formation. In this
      study the effect of a variety of demulsifiers on lysozyme extraction was
      evaluated in terms of their influence on the separating properties of the
      emulsion, water content (Wo), and, extraction yield and kinetics from both buffer
      and hen egg white. In addition, the use of a low shear contactor (a Graesser or
      'raining bucket') was assessed in terms of its suitability as a RM contactor. It
      was found that most of the demulsifiers reduced the settling time of the
      emulsion, and enhanced the yield and kinetics of lysozyme extraction from hen egg
      white. It was hypothesised that this was due to the demulsifier displacing the
      lysozyme from the interface and preventing the protein unfolding and
      precipitating. This effect was found to depend on both the generic type of
      demulsifier, and its concentration.

PMID- 10892542
TI  - One step purification of peanut phospholipase D by precipitation with alginate.
AB  - A simple titrimetric assay with soybean lecithin has been used for screening
      phospholipase D activity from some plant sources, viz. peanut, wheat germ,
      cabbage and carrot. The enzyme from peanut has been purified by binding to
      alginate which is a water soluble polymer. The purification consisted of co
      precipitation of enzyme with alginate upon addition of 0.06 M Ca++. The enzyme
      was eluted from the polymer using 0.2 M sodium chloride. The activity recovery
      was 61% with 34 fold purification.

PMID- 10892543
TI  - Improved purification of Candida boidinii formate dehydrogenase.
AB  - Formate dehydrogenase (FDH, EC 1.2.1.2) from Candida boidinii was purified to
      homogeneity. The two step procedure comprised anion exchange chromatography (2.9
      fold purification, 85% step yield, elution with 35 mM KCl), followed by dye
      ligand affinity chromatography on immobilized Cibacron Blue 3GA (1.4-fold
      purification, 75% step yield, elution with 0.15 mM NAD+/2 mM Na2SO3). The
      procedure afforded FDH at 63.8% overall yield and a specific activity of 7.2
      units/mg. The purity of the final FDH preparation was evaluated by sodium dodecyl
      sulphate polyacrylamide gel electrophoresis (SDS-PAGE), high performance gel
      filtration liquid chromatography (gfHPLC) and N-terminal amino acid sequencing.
      The analytical techniques showed the presence of a single polypeptide chain that
      corresponds to the molecular weight of 41 kDa (as determined by SDS-PAGE) and 81
      kDa (as determined by gfHPLC).

PMID- 10892544
TI  - Aqueous polymer two-phase systems formed by new thermoseparating polymers.
AB  - A set of new polymers that can be used as phase forming components in aqueous two
      phase systems is presented. All polymers studied have thermoseparating properties
      i.e. form one separate polymer enriched phase and one aqueous solution when
      heated above the critical temperature. This property makes the polymers
      attractive alternatives to the polymers used in traditional aqueous two-phase
      systems such as poly(ethylene glycol) (PEG) and dextran. The thermal phase
      separation simplifies recycling of the polymers, thus making the aqueous two
      phase systems more cost efficient and suitable for use in large scale.
      Thermoseparating polymers studied have been copolymers of ethylene oxide and
      propylene oxide (EO-PO), poly (N-isopropylacrylamide) (poly-NIPAM), poly vinyl
      caprolactam (poly-VCL) and copolymers of N-isopropylacrylamide and vinyl
      caprolactam with vinyl imidazole (poly(NIPAM-VI) and poly(VCL-VI), respectively).
      In addition, the copolymer poly(NIPAM-VI) has the property to be uncharged at pH
      above 7.0 and positively charged at lower pH. This allows the partitioning of
      protein to be directed by changing the pH in the system instead of the
      traditional addition of salt to direct the partitioning. Hydrophobically modified
      EO-PO copolymer (HM-(EO-PO)) with alkyl groups (C14) at both ends forms two-phase
      system with for example poly(NIPAM-VI). The phase diagram for poly(NIPAM-VI)/HM
      (EO-PO) was determined and the model proteins lysozyme and BSA were partitioned
      in this system. For BSA in poly(NIPAM-VI)/HM-(EO-PO) system a change in pH from
      8.0 to 5.4 results in a change of partition coefficient from K = 0.8 to K = 5.1,
      i.e. BSA could be transferred from the HM-(EO-PO) phase to the poly(NIPAM-VI)
      phase. BSA partitioning in poly(NIPAM-VI)/HM-(EO-PO) system allows quantitative
      BSA recovery, and recoveries of poly(NIPAM-VI) and HM-(EO-PO) were 53% and 92%,
      respectively, after the thermoseparation step.

PMID- 10892546
TI  - Smoking and health, with a note on kidney cancer.

PMID- 10892545
TI  - The cultural history of smoking.

PMID- 10892547
TI  - Effects of cigarette smoking on systemic hemodynamics.

PMID- 10892548
TI  - Acute effects of cigarette smoking on renal hemodynamics.

PMID- 10892549
TI  - Effects of chronic cigarette smoking on the kidney.

PMID- 10892550
TI  - Effect of cigarette smoking on renal function and vascular endothelium.

PMID- 10892551
TI  - Cigarette smoking, DNA variants in endothelial nitric oxide synthase gene and
      vascular disease.

PMID- 10892552
TI  - Ischemic renal disease: impact of cardiovascular risk factors and smoking.

PMID- 10892553
TI  - Cigarette smoking and early stage primary renal disease.

PMID- 10892554
TI  - Cigarette smoking and diabetic nephropathy.

PMID- 10892555
TI  - Cigarette smoking and other inhaled toxins in anti-GBM disease.

PMID- 10892556
TI  - Cigarette smoking and pauci-immune extracapillary glomerulonephritis with ANCA
      associated idiopathic systemic vasculitis. A retrospective study.

PMID- 10892557
TI  - Smoking as a risk factor for end-stage renal failure in patients with primary
      renal disease.

PMID- 10892558
TI  - Effect of smoking on urinary NOx and cGMP excretion in IgA nephropathy and in
      health.

PMID- 10892559
TI  - Lipoperoxidation in hemodialysis patients: upregulation of 5-lipoxygenase
      activity and expression in peripheral blood mononuclear cells.

PMID- 10892560
TI  - Tobacco smoking and renal-cell carcinoma. An overview.

PMID- 10892561
TI  - Body growth and food intake in moderately and severely malnourished rats.
AB  - A longitudinal study with eighty-six rats (Rattus norvegicus albinus var. Wistar)
      of both sexes was made. The aim was to express adaptability to malnutrition in
      terms of Age-of-Fitness Point (AFP) and Trend-to-Fitness Stage (TFS). The AFP
      means the age in which both control and malnourished animals show the same
      Relative Food Intake (RFI) value, expressed in mg of food intake per g of body
      weight. The TFS means the percent of RFI reached by the malnourished animals at a
      given age stage. A TFS=70 for example, means that the animals have to gain 30% of
      RFI to reach its AFP. Growing animals were submitted to one of the following
      treatments: control (fed on a stock diet ad libitum), moderate malnutrition (fed
      on 1/2 of the daily stock diet of a control of the same age and sex) and severe
      malnutrition (fed on 1/3 of the mentioned diet). Body weight and food intake of
      all of the animals were registered every ten days, when they were from 20 to 80
      days old. Relative Food Intake (RFI) was calculated dividing the food intake (mg)
      of each animal/day by its respective body weight (g). The RFI data series
      belonging to each sex and treatment was obtained. The significance of the three
      independent variables (age, sex, and nutrition) was tested by multiple
      regressions. Covariation and degree of linearity between RFI and age were tested
      by simple correlation and simple regression tests. The intercepts of the
      regressions were all significant. For both sexes they were greater in controls
      than in the moderately malnourished group, in the latter being greater than in
      the severely malnourished group. The slopes were significant and negative in all
      of the groups. While, in males and females, control and moderately malnourished
      rats showed little differences, the severely malnourished slopes were,
      respectively, 3.2 and 2.4 times lower than in controls. In controls there were
      sexual differences for RFI correlated with age which were not present in the
      malnourished groups. The AFP was calculated by extrapolation: 80-90 days of age
      in males, with RFI of 80 mg/g, and 100-110 days of age in females, with RFI of 70
      mg/g. In males TFS was 29.5% and 88.6 % in moderate and severe malnutrition,
      respectively. In females these values were 9.1% and 63.2%, respectively. Sexual
      dimorphism in TFS was significant in the moderately malnourished animals and
      nonsignificant in the severely malnourished ones.

PMID- 10892562
TI  - The ontogeny of myostatin, follistatin and activin-B mRNA expression during
      chicken embryonic development.
AB  - The developmental pattern of myostatin, follistatin and activin-B genes in chick
      embryonic development was investigated. Total RNA was isolated from whole embryos
      on each of embryonic days (E) 0 to 6, from cranial halves of the embryo at E7 to
      8, and from pectoralis muscle tissues at E9 to 20. Myostatin, follistatin and
      activin-B cDNAs were synthesized by reverse-transcription polymerase chain
      reaction (RT-PCR). Myostatin expression was first detected in embryos as early as
      the blastoderm stage (unincubated embryo, stage 1, E0). Myostatin mRNA
      concentration declined approximately 5 fold by E2 and remained lower through E6.
      Levels then increased 3 fold on E7 and plateaued through E16. Follistatin mRNA
      was first detected in the blastoderm stage of chick embryos. Overall follistatin
      mRNA increased 6 fold from E1 to E20 of development. Follistatin levels declined
      on E1 (approximately 2 fold) and remained low through E9. Follistatin mRNA
      reached the highest level prior to hatching. Activin-B mRNA from the whole embryo
      preparations (E0-E6) varied as the embryo matured. Overall activin-B gene
      expression from E11 to E20 appeared to decline (approximately 3.5 fold). This
      pattern is opposite of follistatin during the same period which is consistent
      with the opposing functions of these two proteins. We suggest that follistatin,
      activin-B and myostatin play an important role in embryogenesis and skeletal
      muscle development of the chick embryo. This study represents the first
      comprehensive report of myostatin mRNA patterns in chicken embryos.

PMID- 10892563
TI  - Brain-tissue accumulation of fluorescent age pigments in four poeciliid fishes
      (cyprinodontiformes) and the estimation of "biological age".
AB  - The concept of an intrinsic "biological age" or "physiological age" is very
      important in comparative ecological and evolutionary studies, but its
      implementation has been problematic. Although many authors have discussed the
      importance of intrinsic measures of age over the past 75 years, only Reiss (1989
      ) has proposed an operational definition in terms of cumulative metabolism;
      however, Reiss' measure cannot be easily applied to assessing the age of
      individual organisms. Measurement of the level of accumulation of fluorescent age
      pigments (particularly lipofuscins) in post-mitotic tissues, which seems to occur
      at a rate proportional to cumulative metabolism, in principle provides a
      mechanism for estimating the biological age of individual organisms. This study
      has shown that brain-tissue FAP levels vary in direct proportion to chronological
      age and body size within four species of poeciliid fishes, and has documented
      interspecific differences in rate of accumulation of fluorescent age pigments,
      differences that seem to be a function of the degrees of relatedness. Rather than
      proposing that FAP level by itself be used as a measure of biological age,
      however, I propose that it be used in conjunction with other estimates, such as
      chronological age and body size, to derive a composite "age factor."

PMID- 10892564
TI  - Male/female dimorphism: pubertal change in standing height.

PMID- 10892565
TI  - Dexamethasone inhibits endotoxin-induced changes in calcium and contractility in
      rat isolated papillary muscle.
AB  - This study investigates whether endotoxin-induced contractile dysfunction is
      associated with a defect in the modulation of calcium homeostasis and the
      potential mechanisms involved. Treatment of rats in vivo with endotoxin
      significantly decreased the magnitude of contractile transients in electrically
      stimulated left ventricular papillary muscle isolated after an equilibration
      period of 6 hours. Although no significant difference was found in the peak
      intracellular calcium concentration ([Ca2+]i) between the endotoxin-treated and
      control groups, resting [Ca2+]i) was significantly elevated in the endotoxin
      treated group, producing a smaller Ca2+ transient (basal-peak difference) in this
      group. Pretreatment of rats with dexamethasone prevented the endotoxin-induced
      decrease in peak tension and inhibited the elevation in resting [Ca2+]i, with a
      resultant maintenance of Ca2+ transient magnitude. Similar observations were made
      during stimulation of the muscles by the beta-adrenoceptor agonist, isoprenaline.
      These results show that endotoxin-induced reduction of cardiac contractile
      performance is mediated, at least in part, by elevating resting [Ca2+]i, and a
      glucocorticoid protected from these negative effects. While endotoxin reduces the
      magnitude of the Ca2+ transient it does not alter peak [Ca2+]i availability.
      Further investigation is required to determine whether endotoxin decreases
      contractile performance by reducing the sensitivity of cardiac myofilaments to
      calcium.

PMID- 10892566
TI  - Xestospongin C is an equally potent inhibitor of the inositol 1,4,5-trisphosphate
      receptor and the endoplasmic-reticulum Ca(2+) pumps.
AB  - Xestospongins, a group of macrocyclic bis-1-oxaquinolizidines isolated from the
      Australian sponge, Xestospongia species, are potent blockers of the inositol
      1,4,5-trisphosphate (IP(3))-induced Ca2+ release in bi-directional Ca2+-flux
      conditions. We have now studied the effects of xestospongin C on the (45)Ca2+
      uptake and the uni-directional (45)Ca2+ efflux in permeabilized A7r5 smooth
      muscle cells. Xestospongin C not only inhibits the IP(3)-induced Ca2+ release,
      but is also an equally potent blocker of the endoplasmic-reticulum Ca2+ pump,
      while it has no effect on the passive Ca2+ leak. The inhibition of the IP(3)
      receptor did not depend on the IP(3), Ca2+ or ATP concentration. Xestospongin C
      can, therefore, not be considered as a selective blocker of IP(3) receptors.

PMID- 10892567
TI  - Na+-Ca2+ exchange and Ca2+ efflux in transfected Chinese hamster ovary cells.
AB  - The objective of this study was to assess the contribution of Na+-Ca2+ exchange
      activity to Ca2+ efflux at various cytosolic Ca2+ concentrations ([Ca2+]i) in
      transfected Chinese hamster cells expressing the bovine cardiac Na+-Ca2+
      exchanger. Ionomycin was added to fura-2 loaded cells and the resulting [Ca2+]i
      transient was monitored in Ca2+-free media with or without extracellular Na+. The
      presence of Na+ reduced both the amplitude and duration of the [Ca2+]i transient.
      Na+ had similar effects when the peak of the [Ca2+]i transient was buffered to
      100 nM by cytosolic EGTA, or when Ca2+ was slowly released from internal stores
      with thapsigargin. Ca2+ efflux following ionomycin addition was directly measured
      with extracellular fura-2 and followed a biphasic time course (t(1/2)
      approximately = 10 s and 90s). The proportion of total efflux owing to the rapid
      phase was increased by Na+ and reduced by EGTA-loading. Na+ accelerated the
      initial rate of Ca2+ efflux by 65% in unloaded cells but only by 16% in EGTA
      loaded cells. In both cases, the stimulation by Na+ was less than expected, given
      the pronounced effects of Na+ on the [Ca2+]i transient. We conclude that the
      exchanger contributes importantly to Ca2+ efflux activity at all [Ca2+]i values
      above 40 nM. We also suggest that Ca2+ efflux pathways may involve non-cytosolic
      or local routes of Ca2+ traffic.

PMID- 10892568
TI  - SR compartment calcium and cell apoptosis in SERCA overexpression.
AB  - The relationship between SR Ca2+ ATPase (SERCA) activities, cell calcium level,
      SR calcium store and cell cycle events is not clearly understood. We studied
      SERCA overexpression in Cos cells using an adenovirus vector. Twofold increases
      in SERCA mRNA and in protein were correlated with a 2.3-fold and a 1.6-fold
      paralleled increase in SR calcium pump activity (R = 0.97 and R = 0.99
      respectively). Dose-related apoptotic cell death was associated with SERCA
      overexpression (R = 0.92). When serum was reduced to 4%, cell apoptosis further
      increased from 20.7 +/- 4.8% to 47.5 +/- 12.9% (M+/-SD; P<0.05; n=3). Flow
      cytometry identified cell cycle arrest at the G2/M phase. The interleukin-1
      converting enzyme (ICE) inhibitor z-VAD-fmk reduced apoptosis for low-, medium-
      and high-expressing constructs, whereas the CPP-32 inhibitor z-DEVD-fmk had no
      effect. Flow cytometry using Fluo-3 and Fura-Red revealed a 1.5-fold higher basal
      calcium and a 10-fold SR calcium overload. ICE inhibitor z-VAD-fmk did not alter
      calcium loading. An epitope-tagged SERCA mutant, which has no intrinsic Ca2+-pump
      activities, had a much smaller effect on the SR calcium. These findings suggest
      that SERCA2A overexpression has an intrinsic role in altering cell-cycle
      progression, augmenting cellular and SR calcium loading, and precipitating ICE
      protease-mediated apoptosis; this represents as a novel model for primary SR
      calcium overload and associated cell apoptosis.

PMID- 10892569
TI  - Mechanism of fluoride action on the L-type calcium channel in cardiac ventricular
      myocytes.
AB  - The modulatory actions of fluoride on the function of the dihydropyridine
      sensitive (L-type) Ca2+ channel were studied in rabbit cardiac myocytes. In cell
      attached voltage-clamp experiments, using barium as the charge carrier, fluoride
      increased the activity of the Ca2+ channel dose-dependently. Low concentrations
      (<10 mM) of fluoride increased the number of traces with channel activities, and
      decreased the number of traces without channel activities, resulting in a net
      increase in the open-channel probability. The effect of 5 mM fluoride on the Ca2+
      channel was inhibited by the presence of non-hydrolyzable guanosine diphosphate
      analog in the cell. On the other hand, high concentrations (>10 mM) of fluoride
      increased the open-channel duration, resulting in a marked increase in open
      channel probability. A pretreatment of myocytes with a phosphatase inhibitor,
      okadaic acid, virtually abolished the additional effect of fluoride on the open
      channel duration or open probability. A concentration of up to 75 mM fluoride had
      no effect on the Ca2+-channel activity when the myocytes were pretreated with a
      potent inhibitor of protein kinases, indicating that fluoride increased the Ca2+-
      channel activity via modulation of the phosphorylation state of the myocyte or
      the channel protein alone.

PMID- 10892570
TI  - Spatiotemporal analysis of [Ca2+]i rises in mouse eggs after intracytoplasmic
      sperm injection (ICSI).
AB  - Intracytoplasmic sperm injection (ICSI) into mammalian eggs induces repetitive
      rises in intracellular Ca2+ concentration ([Ca2+]i) which are the pivotal signal
      in fertilization. Spatiotemporal aspects of [Ca2+]i rises following ICSI into the
      periphery of mouse eggs were investigated with high-speed confocal microscopy.
      The first Ca2+ response was generated 25-30 min after ICSI, when [Ca2+]i
      increased slowly and reached a certain level. The [Ca2+]i rise occurred
      synchronously over the ooplasm, attained the peak in 40-70 s, and lasted for 5-7
      min. Succeeding Ca2+ responses occurred at intervals of 20-30 min, associated
      with the faster rate of [Ca2+]i rise and the shorter duration as Ca2+
      oscillations progressed. The [Ca2+]i rises took the form of a wave that started
      from an arbitrary cortical region, but not from the vicinity of the injected
      sperm head. The Ca2+ wave became more pronounced and propagated across the egg
      faster in the later Ca2+ responses. An artifactual [Ca2+]i rise was inevitably
      produced during the ICSI procedure. The larger artifact affected the subsequent
      first Ca2+ response, resulting in the faster [Ca2+]i rise (time to peak, 10-20
      s), slight spatial heterogeneity of [Ca2+]i rise in the ooplasm (but not a wave)
      and the shorter duration (3-4 min). The artifact slightly affected the amplitude
      of the second Ca2+ response, but little affected the later Ca2+ responses. It is
      suggested that the factor(s) that leaked out of the injected spermatozoon
      diffuses to a wide area and sensitizes Ca2+ channels of the endoplasmic reticulum
      to induce Ca2+ release synchronously over the ooplasm. The enhanced sensitization
      leads to propagating Ca2+ release initiated from the cortex that is more
      sensitive to the sperm factor.

PMID- 10892571
TI  - Evidence that Ca2+-waves in Xenopus melanotropes depend on calcium-induced
      calcium release: a fluorescence correlation microscopy and linescanning study.
AB  - The neuroendocrine melanotrope cell displays Ca2+ oscillations that are build up
      by several discrete Ca2+ rises ('steps'). Each step is linked to Ca2+-entry
      across the plasma membrane via voltage-operated calcium channels and associated
      with a fast Ca2+-wave travelling from the plasma membrane to the central parts of
      the cell. Previously, linescanning with confocal laser scanning microscopy (CLSM)
      supported that these waves have high speeds (between 30 and 80 microm/s), which
      is considered indicative of the involvement of a calcium-induced calcium release
      (CICR) mechanism in fast-wave propagation. However, to firmly establish the
      presence of a CICR mechanism one must rule out the possibility that the Ca2+
      signal is artifactually accelerated by the presence of a highly mobile Ca2+ probe
      and also eliminate imaging artifacts inherent to single wavelength imaging. In
      the present study both problems are addressed. Mobility and intracellular
      distribution of a generally used Ca2+ probe, Oregon-green 488 BAPTA-1 (O-green
      1), were established using fluorescence correlation microscopy. We then used the
      ratio signal of co-loaded O-green-1 and Fura-Red to quantify the relative [Ca2+]i
      during linescanning. It was found that O-green-1 displays different diffusion
      times when regions near the plasma membrane and in the center of the cell are
      compared. However, the calculated diffusion constant of the probe was too low to
      account for the observed high speed of the Ca2+ wave. In conclusion, we
      established the authenticity of the high speed of Ca2+-waves in Xenopus
      melanotropes, providing evidence for the involvement of a CICR mechanism in wave
      propagation.

PMID- 10892572
TI  - Focal sarcoplasmic reticulum calcium stores and diffuse inositol 1,4,5
      trisphosphate and ryanodine receptors in human myometrium.
AB  - Intracellular calcium stores of human uterine myocytes in primary and second
      passage cell culture were visualized using the low-affinity calcium-sensitive
      fluorescent dye, fluo-3FF. The calcium stores appeared as numerous small (0.2-0.5
      microm diameter) focal fluorescences. The stores were not depleted by exposing
      the cells to oxytocin or ryanodine under standard conditions. The stores were
      rapidly depleted by oxytocin or ryanodine exposure when sarcoplasmic reticulum
      (SR) calcium re-uptake was inhibited by pretreatment with thapsigargin.
      Immunofluorescence experiments indicated that both ryanodine and inositol 1,4,5
      trisphosphate (IP(3)) receptors were smoothly distributed throughout the SR, and
      neither receptor co-localized with the calcium stores. Since IP(3) and ryanodine
      calcium channels are tightly associated with their receptor, these results
      suggest that SR calcium release occurs via second messenger channels that are
      remote from the SR calcium stores. These observations are consistent only with a
      mechanism for release of calcium stores where the SR serves three functions: (1)
      as site of calcium storage, (2) as the structure that contains the IP(3)- and
      ryanodine receptors and their associated release channels, and (3) as a conduit
      between the calcium stores and the release channels.

PMID- 10892573
TI  - Breast cancer: challenges and opportunities.
AB  - The pace of research in breast cancer has picked up significantly in recent
      years, due to both increased public awareness and improved technology. The
      availability of many new agents in an already crowded field has resulted in
      several challenges (both practical and conceptual) for the research community.
      This report suggests that the "business-as-usual" approach to drug development
      has important limitations rendering it inadequate to the current research
      climate. Future drug development, in the form of biologically targeted therapies,
      offers the best hope for defeating this disease.

PMID- 10892574
TI  - Future directions in the treatment of non-small cell lung cancer.
AB  - In recent years significant advances have been made in the treatment of
      metastatic non-small cell lung cancer. These advances have been due to both the
      discovery of new, more active drugs and an enhanced understanding of the biology
      of the disease, which has guided treatment decisions. Today, agents such as
      paclitaxel, docetaxel, vinorelbine, irinotecan, and gemcitabine are used in
      combinations that have demonstrated higher overall response rates and longer
      median overall survival durations than the previous generation of regimens based
      primarily on cisplatin, etoposide, and vinblastine. Of these new agents,
      paclitaxel has been the most widely studied and has demonstrated considerable
      activity when administered in a wide range of doses and schedules. Regimens with
      significant activity include paclitaxel and carboplatin as well as paclitaxel,
      carboplatin, and gemcitabine. However, because the optimal doses and schedules
      have not been clearly elucidated, current research efforts continue to focus on
      variations of these regimens. Just as advances have been made in the treatment of
      metastatic disease, it also has been clearly demonstrated that preoperative
      chemotherapy (+/- radiation) dramatically improves the overall survival for
      patients with stage III disease. The identification of growth factors, growth
      factor receptors, oncogenes, and tumor suppressor genes, which influence this
      disease, is providing new targets for future treatment strategies. Likewise, new
      therapeutic entities such as antiangiogenesis agents and matrix metalloproteinase
      inhibitors are being evaluated.

PMID- 10892575
TI  - Limited-stage ovarian carcinoma.
AB  - No effective screening test for ovarian carcinoma exists. Consequently, only 25%
      of patients have limited (FIGO stage I-II) disease, and most of these will be at
      high risk for recurrence. Management requires categorization of the primary
      neoplasm as low or high risk. Those at low risk have all the following
      characteristics: grade I disease limited to the ovary, no tumor on the surface of
      the ovary, negative peritoneal cytology, and no ascites. The 5-year disease-free
      survival rate exceeds 90%; hence, surgical resection (total abdominal
      hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and careful surgical
      exploration) followed by observation is the treatment of choice. Patients at high
      risk have one or more of the following features: grade 2 or 3 disease, disease
      outside of the ovary, tumor on the surface of the ovary, positive peritoneal
      cytology, or ascites. Recurrence rates approximate 40%. Platinum-based adjuvant
      chemotherapy yields a recurrence rate approximately half that obtained with no
      adjuvant therapy.

PMID- 10892576
TI  - Chemotherapy for ovarian cancer.
AB  - Prospective randomized trials have established carboplatin plus paclitaxel as the
      preferred combination chemotherapy for patients with advanced ovarian cancer.
      However, clinical issues remain to be determined regarding the use of this
      regimen. These include the optimization of dose and schedule, the role of
      maintenance therapy, any potential role of high-dose chemotherapy with
      hematologic support, and the role of intraperitoneal chemotherapy. In addition,
      new drug combinations that add new agents (eg, topotecan, gemcitabine, or
      etoposide) to the standard two-drug combination of paclitaxel plus carboplatin
      need to be evaluated.

PMID- 10892577
TI  - Androgen-independent prostate cancer: not so chemorefractory after all.
AB  - Historically, hormone-refractory prostate cancer has not been routinely treated
      with chemotherapy, based on perceptions that single agents were not all that
      active, this patient population was too fragile to receive such therapy,
      responses were virtually impossible to verify given the rarity of bidimensionally
      measurable disease, and, if seen, responses were not clinically meaningful. The
      "truths" of the 1970s and 1980s are the "myths" of the 1990s, but unfortunately
      many physicians continue to propagate these myths despite accumulating data to
      the contrary. Newer combination regimens produce objective response rates in
      measurable disease that rival those seen in other solid tumors that are uniformly
      labeled as "chemosensitive." The widespread use of the serum prostate-specific
      antigen level has allowed the detection of progressive disease at an earlier
      stage in patients with an excellent performance status. Although chemotherapy to
      date has not had an impact on patient survival, quality of life analyses have
      clearly demonstrated improved palliation in treated patients. Hopefully, as this
      knowledge is disseminated more widely, more patients will be offered cytotoxic
      therapy for this currently undertreated disease.

PMID- 10892578
TI  - Dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines: a novel class of
      oral antineoplastic agents.
AB  - Protracted intravenous regimens of 5-fluorouracil (5-FU) produce fewer toxic
      effects and greater response rates than do bolus infusion regimens. An effective
      oral regimen would allow a protracted course of 5-FU without the need for central
      venous lines and the associated increase in complications, such as venous
      thrombosis, infection, and line slippage. Dihydropyrimidine dehydrogenase (DPD)
      is the primary catabolic enzyme of 5-FU. The varying levels of DPD located in the
      gastrointestinal tract make the absorption of oral 5-FU and resultant plasma
      levels erratic. The use of 5-FU pro-drugs and/or DPD inhibitors can overcome this
      absorption problem and allow for oral dosing of fluoropyrimidines. In Japan, oral
      fluoropyrimidines have been used for decades and have gained widespread
      acceptance in the treatment of cancer. More recently, encouraging clinical
      results have led to the development of a new generation of oral
      fluoropyrimidines, commonly referred to as DPD inhibitory fluoropyrimidines, that
      specifically target DPD. Several DPD inhibitory fluoropyrimidines are in advanced
      stages of clinical development in the United States. As studies have shown so
      far, DPD inhibitory fluoropyrimidine can prolong exposure to 5-FU, while causing
      fewer toxic effects, and may have therapeutic advantage over intravenous 5-FU.

PMID- 10892579
TI  - High-performance liquid chromatographic optimization study for the separation of
      natural and synthetic anabolic steroids. Application to urine and pharmaceutical
      samples.
AB  - An HPLC separation of a complex mixture containing 14 androgenic anabolic
      steroids (natural and synthetic) for screening purposes has been carried out. The
      applied optimization method involved the use of binary, ternary and quaternary
      mobile phases containing acetonitrile, methanol or tetrahydrofuran as organic
      modifiers. The effect of different reversed-phase packings and temperature on the
      separation using acetonitrile as organic modifier was studied. The optimum
      separation was achieved by using a water-acetonitrile (55:45, v:v) mobile phase
      and a Hypersil ODS (250 mm x 4.6 mm) 5 microm column (30 degrees C) in about 38
      min, allowing the separation of 14 out of 14 compounds tested (when danazol is
      excluded, 13 out of 14 were separated in 23 min). Calibration graphs were
      obtained using bolasterone, methyltestosterone and canrenone as internal
      standards. Detection limits were in the range 0.012-0.11 microg ml(-1). The
      optimized separation was applied for monitoring the norethindrone acetate
      hydrolysis from tablets and to the analysis, after liquid-liquid extraction, of
      urine samples spiked with steroids.

PMID- 10892580
TI  - Identification of yeast species by fatty acid profiling as measured by gas-liquid
      chromatography.
AB  - An improved rapid method for the identification of yeasts and yeast-like fungi
      from clinical sources which is based on fatty acid profiles obtained by gas
      liquid chromatography (GLC) is described. The fatty acid profile database is
      based upon internal standardisation and using the relative retention times and
      the retention index of the analysed fatty acids. Differentiation between yeast
      species was achieved by the quantitative and qualitative comparison of measured
      fatty acid profiles with those in the database. A total of 1024 clinical isolates
      were analysed by GLC to test the validity of the database. 96.2% of all tested
      samples were identified correctly to the species level by the improved GLC
      method.

PMID- 10892581
TI  - High-performance liquid chromatographic assay to detect hydroxylate and conjugate
      metabolites of propofol in human urine.
AB  - This paper describes a HPLC method for the simultaneous detection of phase I (2,6
      diisopropyl-1-4-quinol and 2,6-diisopropyl-1-4-quinone) and phase II (4-(2,6
      diisopropyl-1-4-quinol)-sulphate, 1-(2,6-diisopropyl-1-4-quinol)-glucuronide, 4
      (2,6-diisopropyl-1-4-quinol)-glucuronide, and propofol-glucuronide) metabolites
      of propofol in human urine samples. Separation was based on a simple mobile phase
      and a reversed-phase chromatographic column. Metabolite identification was
      performed by UV spectrum on a diode-array detector and by LC-APCI-MS. The
      identification was also carried out using in vitro incubation mixtures (cytosol
      and microsomes prepared from liver) from several species: human, rat and rabbit.
      This assay was performed using UV, fluorescence and electrochemical detection
      modes. Each of these was analyzed and discussed.

PMID- 10892582
TI  - Gas chromatographic-mass spectrometric determination of plasma saturated fatty
      acids using pentafluorophenyldimethylsilyl derivatization.
AB  - An improved method for the detection of 11 saturated fatty acids (SFAs) including
      C12:0-C26:0 (even numbers only), C17:0, C19:0 and C23:0 in human plasma by gas
      chromatography-mass spectrometry (GC-MS) with a stable isotope internal standard
      as d3-stearic acid is described. This procedure was based on acidic treatment,
      liquid-liquid extraction, and chemical derivatization prior to instrumental
      analysis. Eleven pentafluorophenyldimethylsilyl-SFA derivatives were well
      separated without any interfering peaks in plasma samples. The characteristic
      ions at M-15, constituting the base peaks in the electron impact mass spectra for
      11 SFAs, permitted their sensitive detection by GC-MS in the selected ion
      monitoring (SIM) mode. The SIM responses were linear with correlation
      coefficients varying from 0.993 to 0.999 in the concentration range of 0.05 to
      approximately 50 microg/ml for the 11 SFAs. The detection limits for SIM of the
      SFAs varied in the range of 0.05 to approximately 10.0 pg. When applied to the
      plasma samples of normal subjects and patients with X-linked adenoleukodystrophy,
      which is one of the hereditary peroxisomal disorders, the present method enabled
      us to determine the SFAs with good sensitivity and good overall precision and
      accuracy within the concentration ranges of 0.14 to approximately 82.35
      micromol/l.

PMID- 10892583
TI  - Optimization of the high-performance liquid chromatographic separation of a
      complex mixture containing urinary steroids, boldenone and bolasterone:
      application to urine samples.
AB  - An HPLC separation of a complex mixture containing 13 urinary anabolics and
      corticoids, and boldenone and bolasterone (synthetic anabolics) has been carried
      out. The applied optimization method involved the use of binary, ternary and
      quaternary mobile phases containing acetonitrile, methanol or tetrahydrofuran as
      organic modifiers. The effect of different reversed-phase packings and
      temperature on the separation was studied. The optimum separation was achieved by
      using a water-acetonitrile (60:40, v/v) mobile phase in reversed-phase HPLC at 30
      degrees C, allowing the separation of all the analytes in about 24 min.
      Calibration graphs were obtained using bolasterone or methyltestosterone as
      internal standards. Detection limits were in the range 0.012-0.107 microg ml(-1).
      The optimized separation was applied to the analysis, after liquid-liquid
      extraction, of human urine samples spiked with steroids.

PMID- 10892584
TI  - Differential diagnosis of homocystinuria by urease treatment, isotope dilution
      and gas chromatography-mass spectrometry.
AB  - Homocystinuria types I, II and III are characterized by different etiologies,
      biochemical abnormalities and therapeutic measures. For this reason, differential
      diagnosis is critical for effective treatment. We describe here a rapid and
      simple procedure for establishing a differential diagnosis of the three types of
      homocystinuria by analyzing the urine of patients. This procedure, which consists
      of urease treatment, stable isotope dilution and GC-MS, enables a simultaneous
      quantification of methionine, homocystine, cystine, methylmalonate, orotate,
      uracil and creatinine. Analysis with this procedure showed that a case of
      homocystinuria type I, who progressed into transient megaloblastic anemia,
      secondarily excreted an increased concentration of orotate, which normalized
      after treatment with folate and vitamin B12. Therefore, the present diagnostic
      procedure not only enables rapid differential diagnosis of homocystinuria, but
      also should prove useful for monitoring the disease state and understanding the
      nutritional condition and therapeutic state of patients, which in turn can be
      used to evaluate the efficacy of treatment.

PMID- 10892585
TI  - Affinity chromatography for purification of two urokinases from human urine.
AB  - A new affinity chromatography (hydrophobic-mediated affinity chromatography),
      which was characterized by the matrix having both affinity site to urokinase and
      hydrophobic site, was established for the purification of urokinase from human
      urine. The hydrophobic affinity matrix (tentatively named PAS in the text) was
      prepared by immobilizing 6-aminocaproic acid on Sepharose CL-6B, followed by a
      coupling p-aminobenzamidine to a part of the hydrophobic site on the matrix. The
      PAS matrix was applied to the purification of urokinase from human urine, and
      high- and low-molecular weight pure urokinases were efficiently obtained in high
      yield by the present method.

PMID- 10892586
TI  - Dynamically-coated capillaries allow for capillary electrophoretic resolution of
      transferrin sialoforms via direct analysis of human serum.
AB  - Transferrin sialoforms with fewer than three sialic acid residues (carbohydrate
      deficient transferrin; CDT) have been implicated as a marker of certain liver
      pathologies. Transferrin sialoforms in human sera from alcoholic and non
      alcoholic patients was analyzed by capillary electrophoresis (CE) using
      diaminobutane (DAB) to dynamically-coat the capillary wall to minimize protein
      wall interactions. Using a DAB concentration of 3 mM, transferrin sialoforms were
      adequately resolved to allow for direct detection of CDT without extensive
      treatment of the sera. Serum immunoglobulins, which migrated close to the CDT
      region, were removed via subtraction with protein A, enhancing the detection of
      CDT. The reproducibility of sialoform separation in dynamically-coated
      capillaries was found to be acceptable with run-to-run relative standard
      deviation values of 0.15% for a sample on a given day and 0.29+/-0.06% for four
      samples day-to-day. These results suggest that dynamic-coating approaches may
      provide a simple alternative to the use of covalently-coated capillaries for the
      CE separation of complex samples.

PMID- 10892587
TI  - Determination of doxepin and desmethyldoxepin in human plasma using liquid
      chromatography-tandem mass spectrometry.
AB  - A sensitive method for the simultaneous determination of doxepin and its active
      metabolite desmethyldoxepin in plasma was established, using high-performance
      liquid chromatographic separation with tandem mass spectrometric detection. The
      samples were extracted with hexane-isoamyl alcohol, separated on a Phenomenex
      Luna C18 5 microm, 150x2.1 mm column with a mobile phase consisting of methanol
      water-formic acid (600:400:0.5, v/v) at a flow-rate of 0.25 ml/min. Detection was
      achieved by a Perkin-Elmer API 2000 mass spectrometer at unit resolution in
      multiple reaction monitoring mode monitoring the transition of the protonated
      molecular ions m/z 280.2, 266.2 and 250.1 to the product ions m/z 107.1, 107.1
      and 191.0 for analyte, metabolite and internal standard (benzoctamine-HCl),
      respectively. TurbolonSpray ionisation was used for ion production. The mean
      recovery for doxepin and desmethyldoxepin was 90% and 75%, respectively, with a
      lower limit of quantification at 0.320 ng/ml and 0.178 ng/ml for the analyte and
      its metabolite, respectively, using 0.5 ml plasma for extraction. This is the
      first assay method described for the simultaneous determination of doxepin and
      desmethyldoxepin in plasma using LC-MS-MS. The method is sensitive enough to be
      used in drug bioavailability studies with doxepin.

PMID- 10892588
TI  - Electrospray ionization mass spectrometry of low-molecular-mass S-nitroso
      compounds and their thiols.
AB  - Low-molecular-mass S-nitroso compounds (R-S-N=O) are potent vasodilators and
      inhibitors of platelet aggregation. This work describes the electrospray
      ionization mass spectrometric (ESI-MS) analysis of physiological and synthetic
      low-molecular-mass S-nitroso compounds and their thiols including S
      nitrosoglutathione, S-nitrosocysteine, glutathione and cysteine. Mass spectra of
      the unlabeled and S-15N-labeled low-molecular-mass S-nitroso compounds
      investigated are characterized by abundant cations due to [M+H]+, [M+Na]+, [(M+H)
      NO]+, [2 M+H]+, and [(2 M+H)-2NO]+. Mass spectra of low-molecular-mass thiols are
      characterized by abundant cations due to [M+H]+, [M+Na]+ and [2M+H]+. Using off
      line electrospray ionization tandem mass spectrometry we unequivocally identified
      S-[15N]nitrosoglutathione in human red blood cells formed after their incubation
      with S-[15N]nitrosocysteine. These results suggest that ESI-MS in combination
      with an appropriate liquid chromatographic system should be a useful analytical
      approach for the on-line quantitative determination of low-molecular-mass S
      nitroso compounds in biological fluids in the presence of their thiols and
      nitrite. Considerations were made about on-line ESI-MS and quantitative
      measurements.

PMID- 10892589
TI  - Purification of human prothrombin from Nitschmann fraction III using DEAE
      membrane radial flow chromatography.
AB  - A DEAE membrane radial column (4x5 cm) was used to purify human prothrombin from
      Nitschmann fraction III and performances of the column were investigated. Sample
      flow-rate of 20-30 ml/min (i.e., 24-36 bed volumes/h) and elution velocity up to
      40 ml/min (i.e., 48 bed volumes/h) were obtained without compromising the
      separation efficiency. Its breakthrough capacity was one-third to half that of
      the commercial DEAE Sepharose Fast Flow media. It was concluded that the novel
      column is an attractive alternate to traditional axial column.

PMID- 10892590
TI  - High-performance liquid chromatographic determination of morphine and its 3- and
      6-glucuronide metabolites by two-step solid-phase extraction.
AB  - To provide more accurate measurement of morphine and its metabolites for a study
      of the genetic differences on morphine response, a method for the analysis of
      morphine and its metabolites is described which has the advantages of increased
      sensitivity and specificity by using a cleaner extraction. The new extraction
      method involves both the hydrophobic isolation on a carbon cartridge and ion
      exchange isolation on ion-exchange resin which has not preliminary been described
      for morphine analysis. The combination of these two steps successfully purified
      drugs from human plasma with maximum removal of interfering substance comparing
      with a conventional C18 cartridge alone. The analytes are quantified by high
      performance liquid chromatography on a reversed-phase C18 column employing a
      mobile phase consisting of 25% acetonitrile in 0.05 M phosphate buffer (pH 2.1),
      and 2.5 mM sodium dodecyl sulfate as the pairing ion with a combination of
      electrochemical and fluorometric detections. The recoveries for morphine (M),
      morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G) and hydromorphone
      after the SPE procedure were 86+/-7.1%, 82+/-6.9%, 79+/-6.0% and 85+/-6.0%,
      respectively. Limits of detection for this method are 0.1 ng/ml for M, and 0.18
      ng/ml for M3G and M6G. Limits of quantitation were approximately 0.25 ng/ml for
      M, and 0.45 ng/ml for M3G and M6G. The present assay was applied to measure M,
      M3G and M6G content in human plasma to test the applicability and suitability of
      this method for clinical and research use.

PMID- 10892591
TI  - Determination of unbound cephalothin in rat blood by on-line microdialysis and
      microbore liquid chromatography.
AB  - A method of analysis for the determination of unbound cephalothin in rat blood
      has been developed. The method was fully automated using an on-line microdialysis
      procedure. A microdialysis probe was inserted into the jugular vein/right atrium
      of male Sprague-Dawley rats to examine the unbound cephalothin level in the rat
      blood after cephalothin administration (50 mg/kg, i.v.). Dialysates were directly
      input to a liquid chromatographic system using an on-line injector. Samples were
      eluted with a mobile phase containing methanol-acetonitrile-100 mM monosodium
      phosphate (pH 5.0) (20:20:60, v/v). The UV wavelength was set at 254 nm for
      monitoring the analyte. Using the retrograde method, at infusion concentrations
      of 1 and 5 microg/ml of cephalothin, the in vivo microdialysis recoveries were
      48.4+/-4.5% and 52.9+/-4.7% for the rat blood (n=6). Intra- and inter-assay
      accuracy and precision of the analyses were < or = 10% in the range of 0.01
      through 10 microg/ml. Pharmacokinetic parameters were calculated from the
      recovery corrected dialysate concentrations of cephalothin versus time data. The
      results suggest that the pharmacokinetics of unbound cephalothin in blood fitted
      best to the two-compartmental model following cephalothin administration (50
      mg/kg, i.v.).

PMID- 10892592
TI  - Sensitive stereospecific determination of acenocoumarol and phenprocoumon in
      plasma by high-performance liquid chromatography.
AB  - We describe a normal-phase HPLC method for the stereospecific determination of R-
      and S-acenocoumarol and R- and S-phenprocoumon with S-warfarin as internal
      standard. The compounds were separated using a Whelk-O1 chiral stationary phase,
      detected by UV at 310 nm and quantified in the internal standard mode. Linearity
      was verified for acenocoumarol in the range of 15-2000 microg/l and for
      phenprocoumon from 15 to 2200 microg/l, respectively. The detection limits were 5
      microg/l for all compounds. The recovery was >84% for R- and S-acenocoumarol and
      >74% for R- and S-phenprocoumon. The imprecision (C.V.) (50-1800 microg/l) for R-
      and S-acenocoumarol was <4.7% within-day and <7.8% between-day. For R- and S
      phenprocoumon the respective values were <5.6% and <5.9%. The accuracy for all
      compounds was 96.5-110%.

PMID- 10892593
TI  - Assessment of nitric oxide synthase activity in vitro and in vivo by gas
      chromatography-mass spectrometry.
AB  - A gas chromatographic-mass spectrometric method for the determination of nitric
      oxide synthase activity is described. The method is based on the gas
      chromatographic-mass spectrometric measurement of L-[15N2]arginine-derived
      [15N]nitrite as its pentafluorobenzyl derivative in the negative-ion chemical
      ionization mode. Application of the method to the analysis of [15N]nitrite
      formation by purified neuronal nitric oxide synthase revealed K(M) values of 3.1
      microM by Hanes and 4.6 microM by Lineweaver-Burk for L-[15N2]arginine. The
      corresponding Vmax values were 0.204 and 0.228 micromol [15N]nitrite min(-1) mg(
      1) NOS, respectively. N(G)-Nitro-L-arginine and N(G),N(G)-dimethylarginine
      (asymmetric dimethylarginine) were identified by this method as the most potent
      enzyme inhibitors. Nitric oxide synthase activity was also assessed in vivo by
      i.v. injection of L-[15N2]arginine in a rat and determination of plasma
      [15N]nitrite and [15N]nitrate. The assay described in this work allows for
      accurate, specific and highly sensitive determination of nitric oxide synthase
      activity in vitro and in vivo.

PMID- 10892594
TI  - Direct analysis of artemisinin in plasma and saliva using coupled-column high
      performance liquid chromatography with a restricted-access material pre-column.
AB  - A previously established HPLC system with post-column derivatization for the
      analysis of artemisinin was coupled to an ADS (alkyl-diol silica) pre-column,
      allowing direct and repetitive injection of protein-rich fluids such as plasma.
      The limit of quantitation for 100 microl of plasma was 10 ng/ml (CV=10.5%) while
      concentrations down to 2 ng/ml could be quantified for 1.00 ml saliva samples
      (CV=11.1%). The system was linear in the tested range of 10-2000 ng/ml for plasma
      and 2-240 ng/ml for saliva samples, respectively. This paper introduces coupled
      column HPLC as a simplified method for the routine analysis of artemisinin in
      biological fluids.

PMID- 10892595
TI  - Optimization of a capillary electrophoresis-electrospray mass spectrometry method
      for the quantitation of the 20 natural amino acids in childrens blood.
AB  - This paper describes useful information on the capillary electrophoresis
      electrospray ionization mass spectroscopy (CE-ESIMS) interfacing for the analysis
      of amino acids (AAs) in standard mixtures and in child plasma blood serum. The
      developed procedure allows quantitation of the 20 natural AAs, in a single run,
      without any derivatization. Limits of detection as low as 3-20 micromol/l (5-30
      pg injected) per analyte were obtained with an efficiency of about 100,000 plates
      and a peak area relative standard deviation below 4%.

PMID- 10892596
TI  - Simultaneous determination of lamivudine and zidovudine concentrations in human
      seminal plasma using high-performance liquid chromatography and tandem mass
      spectrometry.
AB  - A HPLC-MS-MS method was developed and validated to measure lamivudine and
      zidovudine simultaneously in small volumes of human seminal plasma. Sample
      preparation was simple and rapid, requiring 25 microl of sample, the use of
      isotopically labeled lamivudine and zidovudine as internal standards and
      ultrafiltration through a molecular mass cut-off membrane. Lamivudine and its
      internal standard were separated from zidovudine and its internal standard with
      isocratic HPLC. Detection was carried out using tandem mass spectrometry. This
      validated method was used to analyze seminal samples obtained from six HIV
      positive patients prescribed lamivudine and zidovudine.

PMID- 10892597
TI  - Sensitive liquid chromatographic assay for amprenavir, a human immunodeficiency
      virus protease inhibitor, in human plasma, cerebrospinal fluid and semen.
AB  - A sensitive bio-analytical assay for amprenavir, a human immunodeficiency virus
      protease inhibitor, based on reversed-phase liquid chromatography and
      fluorescence detection, is reported. The analyte is extracted from the matrix,
      plasma, cerebrospinal fluid (CSF) or semen, with chloroform using propyl-p
      hydroxybenzoate as an internal standard. After centrifugation, evaporation of the
      organic phase and reconstitution in the eluent, the sample is injected into the
      chromatograph. The analyte is detected spectrofluorometrically at 270 and 340 nm
      for excitation and emission, respectively. The method has been validated in the 1
      1000 ng/ml range for a 50-microl volume of plasma and in the 0.5-50 ng/ml range
      for a 100-microl volume of CSF and semen. The lower limit of quantification was
      0.5 ng/ml in CSF and 1 ng/ml in both plasma and semen. Precision and accuracy
      both meet the current requirements for a bio-analytical assay and are <15% in the
      validated ranges. The assay was successfully used to obtain a concentration-time
      curve of amprenavir in plasma.

PMID- 10892598
TI  - Rapid identification of metallothionein isoforms in liver cytosol fraction by
      capillary zone electrophoresis using EDTA.
AB  - Identification of metallothionein (MT) isoforms on capillary zone electrophoresis
      (CZE) analysis was studied using a linear polyacrylamide-coated capillary at pH
      7.4 and EDTA. The CZE system was able to separate standard (purified and
      commercially available) MT specimens into their isoforms within 10 min. The peaks
      of MT-1 and MT-2 isoforms disappeared on addition of EDTA to the specimen, and
      the disappearance was shown to be time-dependent and dose-dependent, although the
      reason why the peaks decreased is still unclear. A heat-treated cytosol fraction
      prepared from Zn-injected mouse liver showed many major and minor peaks on CZE
      analysis. Two major peaks were identified to be MT-1 and MT-2, respectively, by
      co-injection with the purified MT isoforms. When EDTA was added to the cytosol
      fraction, the two major peaks, MT-1 and MT-2, and three other minor peaks
      disappeared time-dependently. Therefore, each MT isoform in the cytosol fraction
      can be identified by the addition of EDTA, also the peaks are identified by the
      corresponding migration times of purified MTs. Unknown substances like MT sub
      isoforms may also be detected, although this question warrants clarification.
      From these results, it was concluded that the addition of EDTA is useful for
      identification of MT isoforms in cytosol fractions on CZE analysis.

PMID- 10892599
TI  - Improved method for simultaneous determination of L-arginine and its mono- and
      dimethylated metabolites in biological samples by high-performance liquid
      chromatography.
AB  - An improved method has been developed for the determination of L-arginine and its
      methylated metabolites, N(G)-monomethyl-L-arginine (L-NMMA), N(G),N(G)-dimethyl-L
      arginine (asymmetric DMA, ADMA) and N(G),N(G)'-dimethyl-L-arginine (symmetric
      DMA, SDMA) in biological samples. Extraction of these compounds with a strong
      cation-exchange resin AG50W-X8 with L-homoarginine (2-amino-6-guanidinohexanoic
      acid) as an internal standard gave a recovery of more than 70% except for SDMA
      from plasma samples. After extracted samples were converted to fluorescent
      derivatives with o-phthalaldehyde (OPA) in an alkaline medium, the following high
      performance liquid chromatographic separation with a ODS column (wide-pore size,
      300 A) was successfully performed with an isocratic mobile phase system. The
      method permits quantitative determination of L-arginine and its methylated
      metabolites at concentrations as low as 4 microM and 0.18 microM, respectively.
      Using this method, the levels of L-arginine, L-NMMA, ADMA and SDMA in human
      plasma, urine and rat tissue were determined.

PMID- 10892600
TI  - Sensitive method for the determination of ambroxol in body fluids by capillary
      electrophoresis and fluorescence detection.
AB  - A sensitive and rapid capillary electrophoretic method combined with laser
      induced fluorescence detection has been developed for the determination of
      ambroxol. Samples were derivatized with 5 x 10(-4) M fluorescein isothiocyanate.
      A linear relationship between concentration and peak area was obtained in the
      concentration range 0.008-42 microg ml(-1) with a correlation coefficient of
      0.9999. The applicability of the method to serum and urine samples was
      demonstrated. The method is also useful for the determination of ambroxol in
      pharmaceutical preparations.

PMID- 10892601
TI  - Improved highly sensitive method for determination of nicotine and cotinine in
      human plasma by high-performance liquid chromatography.
AB  - A highly sensitive and reliable method for the determination of nicotine and its
      metabolite cotinine in human plasma by high-performance liquid chromatography was
      developed. Nicotine and cotinine were extracted from alkalinized plasma with
      dichloromethane and the volatility of nicotine was prevented by the addition of
      conc. HCl to the organic solvent during evaporation. The sensitivity of
      quantification at 260 nm absorption was improved by using a noise-base clean Uni
      3 to 0.2 ng/ml nicotine and 1.0 ng/ml cotinine. The method was validated over
      linear ranges of 0.2-25.0 ng/ml for nicotine and 1.0-80.0 ng/ml for cotinine. The
      intra-day precision and accuracy were < or = 15.9% relative standard variation
      (RSD) and 89.9-103.5% for nicotine and < or = 8.0% RSD and 98.7-103.0% for
      cotinine. The inter-day precision and accuracy were < or = 17.0% RSD and 94.2
      100.9% for nicotine and < or = 8.2% RSD and 98.0-105.1% for cotinine.

PMID- 10892602
TI  - Balancing policy development and research evidence: are we falling short?

PMID- 10892603
TI  - Are fish oils an effective therapy in mental illness--an analysis of the data.
AB  - OBJECTIVE: To review the literature regarding the use of fish oils in the
      treatment of psychiatric illness. METHOD: A Medline search was conducted in
      September 1999. RESULTS: Five papers have investigated omega-3 fatty acids levels
      in depression. One study used omega-3 fatty acids as an adjunctive therapy in
      bipolar disorder. Four studies used fatty acids as an adjunctive therapy in
      schizophrenia. CONCLUSION: There is a great deal of current research in this
      field. While omega-3 fatty acids levels may be lowered in depression, there are
      no data suggesting that omega-3 fatty acids are effective. One paper indicates
      that omega-3 fatty acids are effective in bipolar disorders. The data on
      schizophrenia are conflicting. Omega-3 and omega-6 fatty acids have proved
      effective. Most of the evidence suggests that the main effect is an improvement
      in negative symptoms. One recent study showed that omega-3 fatty acids had no
      effect on negative symptoms.

PMID- 10892604
TI  - Differences between patients with schizophrenia within and without a high
      security psychiatric hospital.
AB  - OBJECTIVE: To report and discuss differences between schizophrenic patients in
      the community and those in maximum security care. METHOD: Comparison of 193
      community schizophrenic patients with 169 in high security care. Data included
      case notes, interviews and cognitive tests. RESULTS: Compared to high security
      patients, community patients tended to be female and married. They had higher
      school achievement, higher premorbid IQ and better occupational levels, were less
      likely to have a family history of alcohol abuse, to have had police contact and
      to have attempted suicide. They had more frequent shorter psychiatric admissions
      and fewer current and lifetime schizophrenic symptoms. Logistic regression models
      discriminated the groups with considerable accuracy. CONCLUSION: Patients needing
      high security care may be recognizable when schizophrenia is first diagnosed.
      Progression to the State Hospital seems to result from schizophrenia together
      with other factors such as deprivation rather than from a worse schizophrenic
      process per se.

PMID- 10892605
TI  - A longitudinal study of prisoners on remand: psychiatric prevalence, incidence
      and psychopathology in solitary vs. non-solitary confinement.
AB  - OBJECTIVE: To compare two levels of stress (solitary confinement (SC) and non-SC)
      among remand prisoners as to incidence of psychiatric disorders in relation to
      prevalent disorders. METHOD: Longitudinal repeated assessments were carried out
      from the start and during the remand phase of imprisonment. Both interview-based
      and self-reported measures were applied to 133 remand prisoners in SC and 95
      remand prisoners in non-SC randomly selected in a parallel study design. RESULTS:
      Incidence of psychiatric disorders developed in the prison was significantly
      higher in SC prisoners (28%) than in non-SC prisoners (15%). Most disorders were
      adjustment disorders, with depressive disorders coming next. Incident psychotic
      disorders were rare. The difference regarding incidence was primarily explained
      by level of stress (i.e. prison form) rather than confounding factors.
      Quantitative measures of psychopathology (Hamilton Scales and General Health
      Questionnaire) were significantly higher in subjects with prevalent and incident
      disorders compared to non-disordered subjects. CONCLUSION: Different levels of
      stress give rise to different incidence of psychiatric morbidity among remand
      prisoners. The surplus of incident disorders among SC prisoners is related to SC,
      which may act as a mental health hazard.

PMID- 10892606
TI  - The classification of first episode schizophrenia: a cluster-analytical approach.
AB  - OBJECTIVE: This paper examines, using data from the Cantabria First Episode
      Schizophrenia Study, the usefulness of subdividing, using a cluster analysis
      technique, this schizophrenia population into subgroups with similar symptoms
      profiles in terms of SANS and SAPS. METHOD: Diagnostic characteristics were
      determined using the Present State Examination (PSE-9) and the SANS/SAPS.
      Premorbid adjustment was assessed using a scale developed combining the Gittelman
      and Klein's Scales, and the Goldstein's scales. Social Adjustment was evaluated
      using the WHO-DAS. In addition clinical histories were used to assess the
      patients' clinical course. RESULTS: Our schizophrenic patients could be subtyped
      into four categories: negative, positive non-paranoid, simple and disorganized
      schizophrenia. There is an absence of significant association between the
      majority of the variables investigated and the four-cluster model. CONCLUSION:
      Even though our sample could be subtyped into different categories, the model
      does not show predictive power according to the 3-year follow-up data.

PMID- 10892607
TI  - Brain imaging in childhood- and adolescence-onset schizophrenia associated with
      obsessive-compulsive symptoms.
AB  - OBJECTIVE: Childhood- and adolescence-onset schizophrenic patients with obsessive
      compulsive symptoms (OCS) constitute a specific subgroup of schizophrenia. We
      performed magnetic resonance imaging in this group seeking evidence of
      neurodevelopmental insults. METHOD: Thirty-two schizophrenic patients were
      compared with 19 controls. Schizophrenic subjects were divided into 15 patients
      with OCS (SOCS+ group; onset at 15.5 +/- 1.6 years) and 17 without OCS (SOCS-
      group; onset at 15.3 +/- 1.3 years). Areas of the hippocampus, frontal lobe,
      corpus callosum and putamen were analysed morphometrically. RESULTS: The left
      hippocampus was significantly smaller in the SOCS+ group than in the SOCS- and
      control groups. CONCLUSION: Reduced size of the left hippocampus in the SOCS+
      group supports a neurodevelopmental etiology in this subgroup.

PMID- 10892608
TI  - Seasonal variation in hospital admission for bipolar disorder, depression and
      schizophrenia in Tasmania.
AB  - OBJECTIVE: Seasonal variation has been reported for both affective disorders and
      schizophrenia. The current study examines seasonal variation in admissions in
      schizophrenia, depression and bipolar disorder in Tasmania, the southernmost
      state of Australia. METHOD: All admissions with a diagnosis of schizophrenia,
      bipolar disorder and depression in Tasmania between 1983 and 1989 were examined
      for evidence of seasonal variation in admission patterns. RESULTS: Using the
      modified Kolmogorov-Smirnov statistic defined by Freedman no significant seasonal
      variation was found in admissions with diagnoses of mania, depression or
      schizophrenia. There was a significant seasonal variation in admissions with
      schizoaffective disorder (winter peak). CONCLUSION: There is no significant
      seasonal variation in admissions with schizophrenia, depression or bipolar
      disorder in Tasmania. This may be due to a combination of geographical location
      and the stringent test of seasonal variation used in the current study.

PMID- 10892609
TI  - Alcoholism and depression in a Swedish female population: co-morbidity and risk
      factors.
AB  - OBJECTIVE: Our aims were to study associations between depressive disorders and
      alcohol dependence/abuse (ADA) in a female population-based sample, and to
      identify risk indicators common to both depressive disorders and ADA. METHOD:
      Three hundred and sixteen women in a stratified randomized sample were
      interviewed face to face. They were asked about their childhood/adolescence and
      alcohol habits. Clinical lifetime diagnoses according to DSM-III-R were made.
      Depressive disorders includes different mood disorders. RESULTS: Half the women
      with ADA also had a depressive disorder, and 25% of the women with depressive
      disorders also had ADA. Alcohol intoxication before the age of 15 and
      psychological and/or psychiatric problems before the age of 18 years increased
      the risk for ADA and depressive disorders in our study. CONCLUSION: Our results
      support previous findings of an association between depressive disorders and ADA,
      beginning early in life.

PMID- 10892610
TI  - The prevalence of personality disorder among UK primary care attenders.
AB  - OBJECTIVE: To determine the prevalence rate of personality disorder among a
      consecutive sample of UK primary care attenders. Associations between a diagnosis
      of personality disorder, sociodemographic background and common mental disorder
      were examined. METHOD: Three hundred and three consecutive primary care attenders
      were examined for the presence of ICD-10 and DSM-4 personality disorders using an
      informant-based interview. RESULTS: Personality disorder was diagnosed in 24%
      (95% CI: 19-29) of the sample. Personality-disordered subjects were more likely
      to have psychiatric morbidity as indicated by GHQ-12, to report previous
      psychological morbidity, to be single and to attend the surgery on an emergency
      basis. 'Cluster B' personality disorders were particularly associated with
      psychiatric morbidity. CONCLUSION: There is a high prevalence rate of personality
      disorders among primary care attenders. These disorders are associated with the
      presence of common mental disorder and unplanned surgery attendance. Personality
      disorders may represent a significant source of burden in primary care.

PMID- 10892611
TI  - Loss as a determinant of PTSD in a cohort of adult survivors of the 1988
      earthquake in Armenia: implications for policy.
AB  - OBJECTIVE: To study the relationship of post-traumatic stress disorder (PTSD) to
      severity of the disaster experience. METHOD: A sample of 1785 adult participants
      of an epidemiological study initiated in the immediate aftermath of the 1988
      earthquake in Armenia were interviewed about 2 years following the disaster based
      on the NIMH DIS-Disaster Supplement. All 154 cases of pure PTSD were compared
      with 583 controls without symptoms satisfying psychiatric diagnoses of interest.
      RESULTS: PTSD cases included more persons from areas with the worst destruction.
      Having the highest level of education compared to lowest (OR 0.6 [95% CI 0.4
      0.9]), being accompanied at the moment of the earthquake (OR 0.6 [95% CI 0.4
      0.9]) and making new friends after the earthquake (OR 0.6 [95% CI 0.5-0.8]) were
      protective for PTSD. PTSD risk increased with the total amount of loss to the
      family (OR for highest level of loss 4.1 [95% CI 2.3-7.5]). CONCLUSION: Based on
      this large population sample, we believe that early support to survivors with
      high levels of loss may reduce PTSD following earthquakes.

PMID- 10892612
TI  - Unmet needs in the community: can existing services meet them?
AB  - OBJECTIVE: This prospective study of community cases examined: (a) needs for
      care; (b) whether services meet the needs; and (c) personal factors associated
      with unmet needs. METHOD: Two separate 'Needs for Care Assessment Schedule
      Community version' evaluations identified 38 subjects with No Need (NN), 19 with
      Met Needs (MN) and 25 with Unmet Needs (UNM). Other instruments included the
      Diagnostic Interview Schedule-Abridged Version (DISSA) and repeated measures of
      symptoms and social functioning. RESULTS: (a) Cases did not equate needs. (b)
      Services utilization did not equate having met needs. (c) Respondents with UNM
      were more likely to present high rates of lifetime DSM-II-R disorders, no marital
      relationship ever, no employment, high rates of life events, and physical or
      sexual abuse in childhood. They have worse outcome in terms of distress and
      social functioning. CONCLUSION: Personal factors may prevent respondents from
      seeking, engaging and benefiting from treatment.

PMID- 10892613
TI  - Are commonly used self-report inventories suitable for screening postpartum
      depression and anxiety disorders?
AB  - OBJECTIVE: The utility of several self-report symptom inventories were examined
      for detecting postpartum depression (MDD) and anxiety disorders (AD). METHOD:
      Fifty women (3 or 6 months postpartum), at heightened risk for MDD, completed
      several depression and anxiety symptom checklists. Psychiatric diagnoses were
      obtained via SCID interview. RESULTS: Rates of MDD (n=9) and AD (n=9) were
      equivalent in this sample, with minimal diagnostic overlap. While all the self
      report depression inventories screened accurately for MDD, none discriminated AD
      sensitively and reliably. CONCLUSION: The frequent occurrence of AD emphasizes
      the need to identify appropriate screening instruments for postpartum anxiety
      disorders.

PMID- 10892614
TI  - Delusion and desire: erotomania revisited.
AB  - OBJECTIVE: This paper examines the phenomonology in a case of erotomania and
      reviews classical and contemporary treatment options. METHOD: A case of primary
      erotomania is described. RESULTS: Treatment with hospitalization and risperidone
      produced rapid clinical improvement. CONCLUSION: Atypical antipsychotic drugs may
      be useful in the treatment of this interesting syndrome.

PMID- 10892615
TI  - Psychopathological considerations--a useless pseudo-philosophical game?

PMID- 10892616
TI  - The fellowship--An educational experience or cheap labor?

PMID- 10892617
TI  - Managing spasticity in pediatric cerebral palsy using a very low dose of
      botulinum toxin type A: preliminary report.
AB  - OBJECTIVE: To determine if very low doses of botulinum toxin type A (BTX-A) could
      reduce spasticity and improve gait in cerebral palsied children when combined
      with rehabilitation therapy. DESIGN: Ten trainable (IQ > 80), ambulatory, spastic
      diplegic or hemiplegic cerebral palsied children, with no fixed contractures in
      at least one limb, were selected for the study. Patients with a score of 3 on a
      modified Ashworth scale received 0.5 units of BTX-A/kg/muscle. Patients with an
      Ashworth score of 4 received 1.0 BTX-A/kg/muscle. After BTX-A injection, all
      patients received rehabilitation therapy and plastic ankle and foot orthoses for
      walking. RESULTS: Both groups exhibited improvement in Ashworth score and in gait
      within 72 hr of injection with botulinum toxin. Beneficial effects persisted for
      10 to 12 mo in most patients, with three patients exhibiting benefits for at
      least 20 mo. CONCLUSIONS: The results of the present study indicate that a very
      low dose of botulinum toxin type A combined with'rehabilitation therapy resulted
      in a long-lasting decrease in spasticity and an improvement in gait in children
      with cerebral palsy.

PMID- 10892618
TI  - Functional outcomes in patients with brain tumor after inpatient rehabilitation:
      comparison with traumatic brain injury.
AB  - OBJECTIVE: To compare the functional outcome, length of stay, and discharge
      disposition of individuals with brain tumor versus those with acute traumatic
      brain injury. DESIGN: In this study, 78 brain tumor patients were one-to-one
      matched by location of lesion and age with 78 acute traumatic brain injury
      patients. Outcome was measured by using the Functional Independence Measure (FIM
      228) on admission and discharge. The FIM change and FIM efficiency were also
      calculated. FIM data were analyzed in three subsets, i.e., activities of daily
      living, mobility, and cognition. Discharge disposition and rehabilitation length
      of stay were also compared. RESULTS: Demographic variables of race, marital
      status, and payer source were comparable for the two groups. No significant
      difference was found between the brain tumor and the traumatic brain injury
      populations with respect to total admission FIM, total discharge FIM, and FIM
      efficiency. The brain injury population had a significantly greater change in
      FIM. The tumor group had a significantly shorter rehabilitation length of stay
      and a greater discharge to community rate. CONCLUSIONS: Thus, individuals with
      brain tumor can achieve comparable functional outcome and have a shorter
      rehabilitation length of stay and greater discharge to community rate than
      individuals with brain injury.

PMID- 10892619
TI  - Paraspinal electromyography in high lumbar and thoracic lesions.
AB  - OBJECTIVE: To use needle electromyography in the paraspinal muscles to localize
      the root level of a radiculopathy. DESIGN: We collected nine cases of clinically
      proven, isolated high lumbar or thoracic disk herniations of patients who
      underwent MiniPM. Four were from a prospective study of 114 persons with low back
      pain (MiniPM had 100% sensitivity to magnetic resonance imaging-documented high
      disks). RESULTS: In the most medial "S" column, mean MiniPM scores were 0.7 for
      the level above the radiologically documented lesion; 3.1 at the lesion; and 1.6,
      1.6, and 1.1 at the three spinous processes below the lesion. Similar numbers
      were obtained in the "M" column (slightly lateral), with no significant
      differences between S and M. Differences were significant between and at the
      level of the lesion for S (P < 0.06) and M (P < 0.01), and between the lesion
      level and three levels below for the M column (P < 0.01). CONCLUSIONS: These
      findings suggest that paraspinal electromyography has a higher than previously
      reported sensitivity for high lumbar lesions. Electromyography using MiniPM can
      localize some radiculopathies. The individual cases suggest that, consistent with
      the anatomy of the caudi equina, thoracic lesions and lateral lumbar lesions
      denervate only at one level, but more central lumbar lesions also denervate
      distally innervated paraspinal muscles.

PMID- 10892620
TI  - Word finding difficulty as a post-polio sequelae.
AB  - OBJECTIVE: Seventy-nine percent of respondents to the 1990 National Post-Polio
      Survey reported difficulty "thinking of words I want to say," with 37% reporting
      frequent, moderate-to-severe word finding difficulty. This study was undertaken
      to objectively document polio survivors' word finding difficulty and to identify
      its relationship to fatigue, neuropsychologic processes requiring cortical
      activation, and a peripheral marker for brain dopamine secretion. DESIGN: In this
      study, 33 polio survivors were administered the Post-Polio Fatigue Questionnaire,
      Animal Naming and FAS Tests, and tests of attention and information processing
      speed. Plasma prolactin was also measured as a marker for brain dopamine
      secretion. RESULTS: Subjects reporting high fatigue severity and word finding
      difficulty had clinically abnormal or significantly lower Animal Naming Test
      scores compared with subjects with low symptom severity. Impaired performance on
      the most difficult tests of attention and information processing speed were also
      associated with lower scores on the word finding tests. A significant negative
      correlation between Animal Naming Test scores and plasma prolactin suggests that
      a decrement in brain dopamine secretion is related to reduced animal naming
      ability. CONCLUSIONS: These data support the hypothesis that decreased dopamine
      secretion, possibly secondary to poliovirus damage to the basal ganglia, may
      underlie not only fatigue and impaired attention but also word finding difficulty
      in polio survivors.

PMID- 10892621
TI  - Electrically induced recovery of gait components for older patients with chronic
      stroke.
AB  - OBJECTIVE: To compare the gains for chronic stroke patients in volitional gait
      pattern attained from treatment with functional neuromuscular stimulation (FNS)
      and intramuscular electrodes (IM) with gains attained using conventional therapy,
      including treatment with FNS using surface electrodes (surface-stim). DESIGN:
      This single-subject research design consisted of a series of two subjects. Three
      months of conventional therapy and surface-stim were followed by treatment using
      the FNS-IM system. Two stroke patients had cerebrovascular accident 1 or 4 yr
      before the study and ambulated with a cane. Interventions consisted of 3 months
      of conventional exercise and gait training including surface-stim, followed by 7
      14 months of treatment with the FNS-IM system. Treatments occurred up to 3
      times/wk for 1-hr sessions and a home program. Outcome measures consisted of six
      kinematic gait components, as measured by a six-camera video-based data
      acquisition system. Coordination of isolated joint movement was measured
      according to the Fugl-Meyer scale. RESULTS: Both subjects improved during
      conventional therapy to some degree. During FNS-IM treatment, gains were made
      beyond those attained during conventional therapy. Statistically significant
      differences were found between conventional and FNS-IM therapy. CONCLUSIONS: For
      these two subjects, gains in volitional control of gait were made during
      conventional treatment (including surface-stim); for these two subjects during
      FNS-IM treatment, additional gains were made in volitional gait pattern, beyond
      those attained during conventional therapy.

PMID- 10892622
TI  - Transcranial magnetic stimulation and silent period in spasmodic torticollis.
AB  - OBJECTIVE: Our objective was to study the corticobulbar projections to neck
      muscles in cervical dystonia. DESIGN: We compared both the motor evoked
      potentials and the electromyographic silent period after transcranial magnetic
      stimulation from sternocleidomastoid and trapezius muscles in a group of 13
      patients with spasmodic torticollis with those of 20 healthy volunteers. RESULTS:
      With the target muscle at rest, no changes of motor threshold, motor evoked
      potentials latency, and amplitude were observed in dystonic patients. With
      facilitation, the mean amplitude of the motor evoked potentials was increased in
      patients compared with controls, the significant difference being for the
      trapezius muscle, whereas the latency did not differ between groups. The cortical
      silent period was significantly shorter in dystonic patients than in healthy
      subjects in both muscles. The duration of the cortical silent period recorded
      from the sternocleidomastoid muscle showed a positive correlation with the degree
      of neurologic disability assessed by Tsui's scale. No abnormalities of both nerve
      conduction velocity and peripheral silent period by stimulation of accessory
      nerve were found. CONCLUSIONS: These results indicate an impairment of the
      mechanisms of inhibitory motor control in patients with spasmodic torticollis,
      which could be the result of a decrease of the basal ganglia inhibitory output
      over the motor cortex.

PMID- 10892623
TI  - High intensity strength training improves strength and functional performance
      after stroke.
AB  - OBJECTIVE: To evaluate the effects of a progressive resistance strength training
      program on changes in muscle strength, gait, and balance in older individuals 1
      yr after stroke, seven individuals were recruited who were greater than 60-yr
      old, 1 yr after stroke, living at home, and able to follow verbal commands.
      DESIGN: Subjects participated in a 12-wk 2x per wk resistance training program at
      70% of 1 repetition maximum. RESULTS: Lower limb strength improved 68% on the
      affected side and 48% on the intact side during training, with the largest
      increases observed for hip extension (affected side: 88%, P < 0.01; intact side:
      103%, P < 0.001). Repeated chair stand time decreased 21% (P < 0.02). Motor
      performance assessed by the Motor Assessment Scale improved 9% (P < 0.04) and
      static and dynamic balance (Berg balance scale) improved 12% (P < 0.004).
      Progressive resistance training in individuals 1 yr after stroke improves
      affected and intact side lower limb strength and was associated with gains in
      chair stand time, balance, and motor performance. CONCLUSIONS: These results
      support the concept that strength training is an appropriate intervention to
      improve the quality of physical function in older community dwelling stroke
      survivors.

PMID- 10892624
TI  - Post-stroke spasticity management with repeated botulinum toxin injections in the
      upper limb.
AB  - OBJECTIVE: Although the botulinum toxin A (BTX-A) treatment has proved effective
      in spasticity management, no information is available with regard to the effects
      of repeated injections over time. DESIGN: To evaluate the effects of BTX-A on
      moderate or severe upper limb spasticity, an exploratory investigation was
      performed on 28 stroke patients treated for 2 yr or longer and observed for 3 yr.
      Every 3 to 5 mo, each patient received BTX-A injections in upper limb muscles.
      The assessment, performed before and 1 mo after each injection for a median of 28
      mo, included technical and functional objectives and the burden of care. The
      former were evaluated by using the modified Ashworth Scale for spasticity and the
      goniometric measurement of rest position and range of motion; functional
      objectives were evaluated by means of the Frenchay Arm Test and a
      patient/caregiver goals assessment scale. RESULTS: BTX-A treatment was followed
      by an improvement in all technical outcome measures. Motor dexterity scores
      improved in only 8 of 28 patients, vs. daily living activities, which increased
      in all subjects. Although the average dosage injected per session did not change,
      intervals between injections became longer. No relationship between either
      spasticity onset or residual motoricity and response to treatment could be found.
      CONCLUSIONS: This investigation is relevant clinically because repeated BTX-A
      injections show unchanging effectiveness in the management of focal spasticity
      after stroke.

PMID- 10892625
TI  - Functional electrical stimulation on chronic and acute hemiplegic shoulder
      subluxation.
AB  - OBJECTIVE: The present study investigated and assessed the effectiveness of a
      functional electrical stimulation (FES) program in the management of acute and
      chronic shoulder subluxation. DESIGN: By their postonset duration, hemiplegic
      subjects with subluxation participating in the study were placed into a short
      duration group and a long-duration group. Subjects in each group were further
      assigned randomly to either a control subgroup or an experimental subgroup. The
      experimental subgroups of both short and long duration received FES therapy in
      which supraspinatus and posterior deltoid were induced to contract repetitively
      up to 6 hr/day for 6 wk. The duration of the FES session and muscle
      contraction/relaxation ratio were progressively increased as performance
      improved. RESULTS: The experimental subgroup of short duration showed significant
      improvements in reducing subluxation as indicated by x-ray compared with the
      control subgroup of short duration after the first FES treatment. The same effect
      was not shown for the experimental subgroup of long duration. The second FES
      treatment program only resulted in an insignificant change of shoulder
      subluxation for both the short- and long-duration subgroups. CONCLUSIONS: The
      present study suggests that hemiplegic subjects with short postonset duration are
      effectively trained for shoulder subluxation by the first FES treatment program.
      The same FES showed not to be effective when applied to the subjects with
      subluxation of > 1 yr.

PMID- 10892626
TI  - Involuntary masturbation as a manifestation of stroke-related alien hand
      syndrome.
AB  - Alien hand syndrome is a perplexing and uncommon clinical diagnosis. We report an
      unusual manifestation of alien hand syndrome in a 73-yr-old man with a right
      anterior cerebral artery infarct affecting the right medial frontal cortex and
      the anterior portion of the corpus callosum. We conclude that alien hand syndrome
      should be considered in patients who present with a feeling of alienation of one
      or both upper limbs accompanied by complex purposeful involuntary movement.

PMID- 10892627
TI  - Importance of gadolinium enhancement when using MRI to evaluate spinal cord
      pathology.
AB  - Since its introduction, magnetic resonance imaging has become an indispensable
      diagnostic tool for the physiatrist evaluating potential spinal cord pathology.
      Despite ongoing advances in MRI technology and subsequent improved sensitivity,
      significant pathology can still be missed. In this article, we review the
      clinical role of contrast enhancement in visualizing many forms of spinal cord
      pathology.

PMID- 10892628
TI  - The controversy surrounding sacral insufficiency fractures: to ambulate or not to
      ambulate?
AB  - Sacral insufficiency fractures are an often unsuspected cause of low back pain in
      elderly women with osteoporosis who have sustained minimal or no trauma. Many of
      the references in the literature advocate bed rest initially; however, we support
      early mobilization, because most of these fractures are stable and require no
      surgical intervention. With good pain control, patients can begin progressive
      ambulation with assistive devices in a supervised environment and minimize the
      complications of immobility.

PMID- 10892629
TI  - Is hysterectomy obsolete?

PMID- 10892630
TI  - Tempering the enthusiasm for COX-2 inhibitors.

PMID- 10892631
TI  - The role of alcohol use in dyspepsia.

PMID- 10892632
TI  - Uterine fibroid embolization.
AB  - Interventional radiologists have performed uterine artery embolization to treat
      women with emergency uterine bleeding since the 1970s. In this procedure, the
      physician guides a small angiographic catheter into the uterine arteries and
      injects a stream of tiny particles that decreases blood flow to the uterus. It is
      now considered a safe and highly effective nonsurgical treatment of women with
      symptomatic uterine fibroid tumors. Uterine fibroid embolization has several
      advantages over conventional hormonal suppression and surgical procedures,
      including avoidance of the side effects of drug therapy and the physical and
      psychologic trauma of surgery. In addition, after uterine fibroid embolization,
      patients can normally resume their usual activities several weeks earlier than
      they can after hysterectomy. Along with hysteroscopic resection, myolysis and
      laparoscopic myomectomy, uterine fibroid embolization widens treatment options
      for patients who desire to avoid hysterectomy.

PMID- 10892633
TI  - Successful management of the obese patient.
AB  - Obesity is a chronic disease that affects a substantial number of Americans.
      Obesity significantly increases a person's risk of cardiovascular diseases and
      morbidity. Modification of lifestyle behaviors that contribute to obesity (e.g.,
      inappropriate diet and inactivity) is the cornerstone of treatment. Behavior
      modification involves using such techniques as self-monitoring, stimulus control,
      cognitive restructuring, stress management and social support to systematically
      alter obesity-related behaviors. In addition, adjunctive pharmacotherapy can play
      an important role in the routine medical management of obesity.

PMID- 10892634
TI  - Hyponatremia and hypernatremia in the elderly.
AB  - Management of abnormalities in water homeostasis is frequently challenging.
      Because age-related changes and chronic diseases are often associated with
      impairment of water metabolism in elderly patients, it is absolutely essential
      for clinicians to be aware of the pathophysiology of hyponatremia and
      hypernatremia in the elderly. The sensation of thirst, renal function,
      concentrating abilities and hormonal modulators of salt and water balance are
      often impaired in the elderly, which makes such patients highly susceptible to
      morbid and iatrogenic events involving salt and water. Clinicians should use a
      systematic approach in evaluating water and sodium problems, utilizing a
      comprehensive history and physical examination, and a few directed laboratory
      tests to make the clinical diagnosis. Furthermore, clinicians should have a clear
      appreciation of the roles that iatrogenic interventions and lapses in nutrition
      and nursing care frequently play in upsetting the homeostatic balance in elderly
      patients, particularly those who are in longterm institutional and inpatient
      settings.

PMID- 10892635
TI  - Evaluating dysphagia.
AB  - Dysphagia is a problem that commonly affects patients cared for by family
      physicians in the office, as hospital inpatients and as nursing home residents.
      Familiar medical problems, including cerebrovascular accidents, gastroesophageal
      reflux disease and medication-related side effects, often lead to complaints of
      dysphagia. Stroke patients are at particular risk of aspiration because of
      dysphagia. Classifying dysphagia as oropharyngeal, esophageal and obstructive, or
      neuromuscular symptom complexes leads to a successful diagnosis in 80 to 85
      percent of patients. Based on the patient history and physical examination,
      barium esophagram and/or gastroesophageal endoscopy can confirm the diagnosis.
      Special studies and consultation with subspecialists can confirm difficult
      diagnoses and help guide treatment strategies.

PMID- 10892636
TI  - Health issues in men: part I: Common genitourinary disorders.
AB  - Common genitourinary health issues that arise in the care of male patients
      include prostatitis, benign prostatic hyperplasia, urogenital cancers, premature
      ejaculation and erectile dysfunction. Bacterial infections are responsible for
      only 5 to 10 percent of prostatitis cases. Benign prostatic hyperplasia is
      present in 90 percent of men by the age of 85. Common urogenital cancers include
      prostate cancer, transitional cell carcinoma of the bladder and testicular
      cancer. Although an estimated 10 percent of men eventually develop prostate
      cancer, screening for this malignancy is one of the most controversial areas of
      health prevention. Premature ejaculation occurs in as many as 40 percent of men.
      Treatment with tricyclic antidepressants, selective serotonin reuptake
      inhibitors, counseling or behavioral therapy may be helpful. Erectile dysfunction
      affects up to 30 percent of men between 40 and 70 years of age. Stepped therapy
      is a useful approach to this common malady. Good treatment results have been
      obtained with orally administered sildenafil and intraurethrally administered
      alprostadil.

PMID- 10892637
TI  - Cyclooxygenase-2 enzyme inhibitors: place in therapy.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) play a major role in the management
      of inflammation and pain caused by arthritis. A new class of NSAIDs that
      selectively inhibit the cyclooxygenase-2 (COX-2) enzyme has been developed. The
      first COX-2 inhibitors, celecoxib and rofecoxib, are said to provide therapeutic
      benefit with less toxicity than traditional NSAIDs. A third COX-2-selective
      inhibitor, meloxicam, has recently been introduced. COX-2 inhibitors and
      traditional NSAIDs do not appear to differ significantly in their effectiveness
      in alleviating pain or inflammation. They have similar gastrointestinal side
      effects, including abdominal pain, dyspepsia and diarrhea. However, short-term
      studies show fewer gastrointestinal ulcers in patients treated with COX-2
      inhibitors compared with traditional NSAIDs.

PMID- 10892638
TI  - American Urological Association issues guidelines on the management of bladder
      cancer.

PMID- 10892639
TI  - Surgeon General releases mental health report.

PMID- 10892640
TI  - Trends in HIV infection among minority groups.

PMID- 10892641
TI  - The early evolution of the genetic code.

PMID- 10892642
TI  - The impact of comparative genomics on our understanding of evolution.

PMID- 10892643
TI  - Endless forms: the evolution of gene regulation and morphological diversity.

PMID- 10892644
TI  - Evidence for the adaptive evolution of mutation rates.

PMID- 10892645
TI  - Genomic imprinting, mammalian evolution, and the mystery of egg-laying mammals.

PMID- 10892646
TI  - Crystal structure of T7 gene 4 ring helicase indicates a mechanism for sequential
      hydrolysis of nucleotides.
AB  - We have determined the crystal structure of an active, hexameric fragment of the
      gene 4 helicase from bacteriophage T7. The structure reveals how subunit contacts
      stabilize the hexamer. Deviation from expected six-fold symmetry of the hexamer
      indicates that the structure is of an intermediate on the catalytic pathway. The
      structural consequences of the asymmetry suggest a "binding change" mechanism to
      explain how cooperative binding and hydrolysis of nucleotides are coupled to
      conformational changes in the ring that most likely accompany duplex unwinding.
      The structure of a complex with a nonhydrolyzable ATP analog provides additional
      evidence for this hypothesis, with only four of the six possible nucleotide
      binding sites being occupied in this conformation of the hexamer. This model
      suggests a mechanism for DNA translocation.

PMID- 10892647
TI  - Structural organization of the RNA polymerase-promoter open complex.
AB  - We have used systematic site-specific protein-DNA photocrosslinking to define
      interactions between bacterial RNA polymerase (RNAP) and promoter DNA in the
      catalytically competent RNAP-promoter open complex (RPo). We have mapped more
      than 100 distinct crosslinks between individual segments of RNAP subunits and
      individual phosphates of promoter DNA. The results provide a comprehensive
      description of protein-DNA interactions in RPo, permit construction of a detailed
      model for the structure of RPo, and permit analysis of effects of a
      transcriptional activator on the structure of RPo.

PMID- 10892648
TI  - 6S RNA regulates E. coli RNA polymerase activity.
AB  - The E. coli 6S RNA was discovered more than three decades ago, yet its function
      has remained elusive. Here, we demonstrate that 6S RNA associates with RNA
      polymerase in a highly specific and efficient manner. UV crosslinking experiments
      revealed that 6S RNA directly contacts the sigma70 and beta/beta' subunits of RNA
      polymerase. 6S RNA accumulates as cells reach the stationary phase of growth and
      mediates growth phase-specific changes in RNA polymerase. Stable association
      between sigma70 and core RNA polymerase in extracts is only observed in the
      presence of 6S RNA. We show 6S RNA represses expression from a sigma70-dependent
      promoter during stationary phase. Our results suggest that the interaction of 6S
      RNA with RNA polymerase modulates sigma70-holoenzyme activity.

PMID- 10892649
TI  - RAG1/2-mediated resolution of transposition intermediates: two pathways and
      possible consequences.
AB  - During B and T cell development, the RAG1/RAG2 protein complex cleaves DNA at
      conserved recombination signal sequences (RSS) to initiate V(D)J recombination.
      RAG1/2 has also been shown to catalyze transpositional strand transfer of RSS
      containing substrates into target DNA to form branched DNA intermediates. We show
      that RAG1/2 can resolve these intermediates by two pathways. RAG1/2 catalyzes
      hairpin formation on target DNA adjacent to transposed RSS ends in a manner
      consistent with a model leading to chromosome translocations. Alternatively,
      disintegration removes transposed donor DNA from the intermediate. At high
      magnesium concentrations, such as are present in mammalian cells, disintegration
      is the favored pathway of resolution. This may explain in part why RAG1/2
      mediated transposition does not occur at high frequency in cells.

PMID- 10892650
TI  - Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint
      protein Mad2.
AB  - The initiation of chromosome segregation at anaphase is linked by the spindle
      assembly checkpoint to the completion of chromosome-microtubule attachment during
      metaphase. To determine the function of the mitotic checkpoint protein Mad2
      during normal cell division and when mitosis goes awry, we have knocked out Mad2
      in mice. We find that E5.5 embryonic cells lacking Mad2, like mad2 yeast, grow
      normally but are unable to arrest in response to spindle disruption. At E6.5, the
      cells of the epiblast begin rapid cell division and the absence of a checkpoint
      results in widespread chromosome missegregation and apoptosis. In contrast, the
      postmitotic trophoblast giant cells survive without Mad2. Thus, the spindle
      assembly checkpoint is required for accurate chromosome segregation in mitotic
      mouse cells, and for embryonic viability, even in the absence of spindle damage.

PMID- 10892651
TI  - The Drosophila takeout gene is a novel molecular link between circadian rhythms
      and feeding behavior.
AB  - We report the characterization of a novel Drosophila circadian clock-regulated
      output gene, takeout (to). The to amino acid sequence shows similarity to two
      ligand binding proteins, including juvenile hormone binding protein. to mRNA is
      expressed in the head and the cardia, crop, and antennae-structures related to
      feeding. to expression is induced by starvation, which is blocked in all
      arrhythmic central clock mutants, suggesting a direct molecular link between the
      circadian clock and the feeding/starvation response. A to mutant has aberrant
      locomotor activity and dies rapidly in response to starvation, indicating a link
      between locomotor activity, survival, and food status. We propose that to
      participates in a novel circadian output pathway that conveys temporal and food
      status information to feeding-relevant metabolisms and activities.

PMID- 10892652
TI  - Neuroligin expressed in nonneuronal cells triggers presynaptic development in
      contacting axons.
AB  - Most neurons form synapses exclusively with other neurons, but little is known
      about the molecular mechanisms mediating synaptogenesis in the central nervous
      system. Using an in vitro system, we demonstrate that neuroligin-1 and -2,
      postsynaptically localized proteins, can trigger the de novo formation of
      presynaptic structure. Nonneuronal cells engineered to express neuroligins induce
      morphological and functional presynaptic differentiation in contacting axons.
      This activity can be inhibited by addition of a soluble version of beta-neurexin,
      a receptor for neuroligin. Furthermore, addition of soluble beta-neurexin to a
      coculture of defined pre- and postsynaptic CNS neurons inhibits synaptic vesicle
      clustering in axons contacting target neurons. Our results suggest that
      neuroligins are part of the machinery employed during the formation and
      remodeling of CNS synapses.

PMID- 10892653
TI  - Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular
      diversity.
AB  - A Drosophila homolog of human Down syndrome cell adhesion molecule (DSCAM), an
      immunoglobulin superfamily member, was isolated by its affinity to Dock, an
      SH3/SH2 adaptor protein required for axon guidance. Dscam binds directly to both
      Dock's SH2 and SH3 domains. Genetic studies revealed that Dscam, Dock and Pak, a
      serine/threonine kinase, act together to direct pathfinding of Bolwig's nerve,
      containing a subclass of sensory axons, to an intermediate target in the embryo.
      Dscam also is required for the formation of axon pathways in the embryonic
      central nervous system. cDNA and genomic analyses reveal the existence of
      multiple forms of Dscam with a conserved architecture containing variable Ig and
      transmembrane domains. Alternative splicing can potentially generate more than
      38,000 Dscam isoforms. This molecular diversity may contribute to the specificity
      of neuronal connectivity.

PMID- 10892654
TI  - Overall cardiac functional effect of positive inotropic drugs with differing
      effects on relaxation.
AB  - Recent interest in so-called calcium-sensitizing positive inotropic drugs has
      highlighted the potential problem of a positive effect on force development being
      offset, at least partially, by the negative effect that many of these drugs have
      on relaxation. The purpose of this study was to examine the interplay of
      contraction and relaxation in determining the overall cardiac effect of different
      positive inotropic drugs. Using a buffer-perfused isolated rabbit heart
      preparation, we studied four drugs (calcium, dobutamine, EMD 57033, and CGP
      48506) that were given at doses sufficient to increase similarly left ventricular
      pressure-generating capability by approximately 20%. We show that, even though
      they produce equivalent changes in pressure-generating capability, these four
      agents produce dissimilar changes in relaxation capability, with dobutamine
      speeding relaxation, EMD 57033 slowing relaxation, and calcium and CGP 48506
      having little effect of relaxation. Similar relative effects were observed for
      drug-induced changes in the timing of pressure-generation events. These effects
      combine to produce different drug-induced changes in overall cardiac pump
      function judged by the relation between cardiac output and heart rate. Dobutamine
      shifted the maximal cardiac output to a higher heart rate. In contrast, both
      calcium sensitizers shifted the maximum in cardiac output to a lower heart rate,
      whereas calcium had no effect. Thus even though positive inotropic drugs may have
      similar effects on left ventricular pressure generation, the overall benefit of
      such drugs on ventricular pump function will depend on how the drug also affects
      ventricular relaxation and ejection capabilities.

PMID- 10892655
TI  - Long-chain acylcarnitine induces Ca2+ efflux from the sarcoplasmic reticulum.
AB  - Long-chain acylcarnitines increase intracellular Ca2+ (Ca2+i) and induce
      electrophysiologic alterations that likely contribute to the genesis of malignant
      ventricular arrhythmias induced during myocardial ischemia. The mechanisms by
      which long-chain acylcarnitines increase Ca2+i are not known, although it occurs
      in the presence of Ca2+ channel blockade and inhibition of Na+/Ca2+ exchange.
      Long-chain acylcarnitines activate Ca2+ release channels from skeletal muscle
      sarcoplasmic reticulum (SR), but their effect on cardiac SR is unclear. To test
      the hypothesis that long-chain acylcarnitines increase Ca2+i from the SR, SR
      enriched membrane fractions were prepared from rabbit left ventricular myocardium
      using sucrose density-gradient centrifugation and characterized by marker enzyme
      analysis. 45Ca2+ efflux was assessed in the presence or absence of long-chain
      acylcarnitines. Palmitoylcarnitine and stearoylcarnitine produced concentration
      dependent efflux of 45Ca2+, whereas shorter chain acylcarnitines, palmitate, and
      palmitoyl-coenzyme A did not. Pretreatment of cardiac SR vesicles with ryanodine
      did not prevent palmitoylcarnitine-induced Ca2+ release. In addition,
      palmitoylcarnitine did not influence specific [3H]ryanodine binding, suggesting a
      mechanism independent of alterations in ryanodine receptor/Ca2+ release channel
      binding. In summary, long-chain acylcarnitines enhance Ca2+ release from cardiac
      SR vesicles and may thereby mobilize Ca2+i to induce electrophysiologic
      derangements under conditions, such as ischemia, in which these amphiphiles
      accumulate.

PMID- 10892656
TI  - Alpha-human atrial natriuretic peptide, carperitide, reduces infarct size but not
      arrhythmias after coronary occlusion/reperfusion in dogs.
AB  - Carperitide, a recombinant form of alpha-hANP, possesses potent diuretic,
      natriuretic, and vasodilatory activity, and inhibits the renin-aldosterone system
      and sympathetic nervous activity. However, its beneficial effects on ischemic
      myocardium have not been studied fully. We examined carperitide's effects on
      infarct size, hemodynamics, and arrhythmia frequency in anesthetized dogs (n =
      20) subjected to a 90-min coronary artery occlusion/6-h reperfusion protocol.
      Intravenous infusion of carperitide (0.2 microg/kg/min) commenced 15 min after
      occlusion and continued during occlusion/reperfusion. Ventricular fibrillation
      developed in two of 10 control versus three of 10 treated dogs (p = NS).
      Hemodynamics, collateral blood flow to the ischemic wall measured 10 min after
      occlusion, and extent of area at risk were comparable for the two groups. Infarct
      size/area at risk was smaller in treated than in control dogs (4.5 +/- 2.1% vs.
      27.8 +/- 7.8%, respectively; p < 0.05). During occlusion, carperitide tended to
      increase collateral blood flow (+39%) and significantly decreased left
      ventricular systolic pressure (-13%) and end-diastolic pressure (-40%) compared
      with baseline. In control dogs, collateral blood flow tended to decrease (-8.3%),
      whereas most hemodynamic parameters did not change significantly with respect to
      baseline. The number of arrhythmias recorded during occlusion/reperfusion was
      similar in the two groups. Intravenous administration of carperitide limited
      infarct size, but did not reduce incidence of ventricular arrhythmias after 90
      min coronary occlusion/6-h reperfusion in anesthetized dogs. Although the
      beneficial effects of carperitide may be attributable to concomitant changes in
      hemodynamics and collateral blood flow, the precise mechanisms require further
      investigation.

PMID- 10892657
TI  - Transient improvement of acetylcholine responses after short-term oral L-arginine
      in forearms of human heart failure.
AB  - Patients with heart failure exhibit impaired endothelium-dependent vasodilation.
      Although brief intraarterial administration of L-arginine improves endothelium
      dependent vasodilatation in these patients, long-term oral supplementation is
      ineffective. To resolve these conflicting findings, we examined the effect of a
      single, short-term oral dose of L-arginine on serial, hourly forearm vascular
      responses to acetylcholine, sodium nitroprusside, and norepinephrine. Eighteen
      patients with heart failure were randomly allocated in a double-blinded,
      crossover study to receive either a single 20-g oral dose of L-arginine or
      placebo. Vascular responses were measured by forearm venous occlusion
      plethysmography before and at 60, 120, and 180 min after dosage. Blood was
      obtained for measurement of L-arginine and nitric oxide metabolite levels. Oral L
      arginine increased plasma levels by fourfold at 60, 120, and 180 min.
      Vasodilatation to acetylcholine, 37 microg/min, was significantly enhanced at 60
      min (percentage increase in forearm blood flow: placebo, 413 +/- 64%; L-arginine,
      587 +/- 94%; p < 0.05), discernible at 120 min (p = 0.058) but no longer apparent
      at 180 min. Neither basal forearm blood flow, sodium nitroprusside, nor
      norepinephrine responses nor plasma levels of nitrite and nitrate were altered.
      We conclude that although short-term oral supplementation with L-arginine
      produced marked sustained elevation of plasma levels of L-arginine in patients
      with heart failure, responses to acetylcholine were only transiently improved.

PMID- 10892658
TI  - [Arg8]-vasopressin-induced responses on coronary and mesenteric arteries of rats
      with myocardial infarction: the effects of V1a- and V2-receptor antagonists.
AB  - After myocardial infarction, plasma levels of [Arg8]-vasopressin rise to recover
      hemodynamics. The vascular responses to [Arg8]-vasopressin were studied in vitro
      in isolated hearts and mesenteric artery segments of rats with 1-day and 3-week
      old infarcts, in absence and presence of the V1a-receptor antagonist SR-49059 and
      the V2-receptor antagonist OPC-31260. Vascular responses of coronary arteries
      were similar in sham and infarcted hearts. On average, coronary flow was
      maximally decreased by 70 +/- 3% from baseline values of 11.1 +/- 0.3 ml/min,
      with pD2 values of 10.52 +/- 0.05. In mesenteric artery segments of sham and
      infarcted rats, maximal contractile forces, expressed as percentage of
      contraction to 125 mM KCl, were similar (232 +/- 23% and 239 +/- 8%,
      respectively). However, pD2 values from infarcted rats (9.22 +/- 0.07) were
      significantly lower compared with sham (9.55 +/- 0.07) rats. In coronary as well
      as mesenteric vessels, the vasoconstrictor responses, being more susceptible to
      SR-49059 (apparent pA2, between 9.12 and 9.82) than to OPC-31260 (apparent pA2,
      between 6.21 and 6.92), seemed mediated by the V1a receptor. These data indicate
      that in mesenteric but not in coronary vessels, an altered responsiveness to
      vasopressin could be observed. Responses are mediated mainly by the V1a receptor.

PMID- 10892659
TI  - Influence of losartan on alpha-adrenoceptor-mediated vasoconstrictor response in
      humans.
AB  - To evaluate the influence of losartan on alpha-adrenoceptor-mediated
      vasoconstrictor response, we examined dorsal hand vein constrictor response to
      phenylephrine (16-8,192 ng/min) and fingertip vasoconstrictor response to cold
      stimulation with and without pretreatment with losartan (50 mg/day) for 3 days in
      nine healthy men. The effect of coadministration of angiotensin II (Ang II) (0.3
      ng/min) on the venoconstrictor response also was evaluated. Oral pretreatment
      with losartan alone influenced neither of the responses. The log of the infusion
      rate of phenylephrine producing half-maximal venoconstriction [log(ED50)] was
      2.69 +/- 0.10 (mean +/- SEM) for control and 2.68 +/- 0.09 for losartan, and the
      reduction ratio of fingertip blood flow was 68.1 +/- 4.0% for control and 66.7 +/
      4.3% for losartan. Coadministration of Ang II, however, significantly enhanced
      the venoconstrictor response to phenylephrine [log(ED50): 2.43 +/- 0.09, p < 0.05
      vs. control], and the pretreatment with losartan attenuated this effect
      [log(ED50): 2.60 +/- 0.11]. These findings indicate that the alpha-adrenoceptor
      mediated vasoconstrictor response is not influenced by losartan; however, it is
      enhanced by exogenous Ang II, and losartan attenuates the enhanced response, in
      healthy human subjects.

PMID- 10892660
TI  - Echo-dipyridamole stress test evaluation of isosorbide-5-mononitrate efficacy and
      tolerance in patients with coronary heart disease: interplay with sympathetic
      activity.
AB  - In 22 patients with stable myocardial ischemia, we prospectively studied the
      short- and long-term effects of isosorbide-5-mononitrate (5-ISMN) on dipyridamole
      induced myocardial ischemia, the ability of dipyridamole-stress echocardiography
      to evaluate nitrate tolerance, and the role of activation of the neurohumoral
      system in nitrate tolerance development, assessed by modifications of
      catecholamines plasma levels and heart rate variability. After brief treatment
      with 5-ISMN, dipyridamole-stress echocardiography was negative in 19 of 22
      patients (p < 0.001 vs. placebo). During the sustained phase, dipyridamole-stress
      echocardiography was positive after both placebo and active drug (p = NS vs.
      placebo). Heart rate variability showed significantly higher values in power of
      the low frequency (LF) band and low- to high-frequency ratio (L/H), as well as
      significantly lower values of the power of the high-frequency (HF) band (all p <
      0.001) during brief but not during sustained administration of 5-ISMN.
      Norepinephrine plasma levels were significantly higher (p < 0.001) during short
      term 5-ISMN administration but not during the sustained phase. Our results
      indicate that short-term administration of 5-ISMN antagonizes dipyridamole
      induced myocardial ischemia and show the loss of antiischemic efficacy in 95% of
      patients during sustained treatment, demonstrating that dipyridamole-stress
      echocardiography is a useful tool to assess the presence of nitrate tolerance.
      Spectral analysis of heart rate variability and norepinephrine values confirm
      that brief nitrate administration increases sympathetic activity, a possible
      crucial trigger event in the development of nitrate tolerance, whereas prolonged
      nitrate treatment is not associated with prolonged neurohumoral activation.

PMID- 10892661
TI  - Platelet activation is increased in cyclosporin A-induced hypertensive rats.
AB  - One of the most severe side effects of the immunosuppressive agent, cyclosporin A
      (CsA), is increased risk of thromboembolic complications and drug-related
      hypertension. Because platelets might be involved in these processes, we tested
      the possibility of CsA affecting platelet activation, which might contribute to
      these adverse drug reactions. The experiments were done using Wistar rats,
      treated or not (control) with CsA (Sandimmun Neoral), 5 and 30 mg/kg/day, for 7
      weeks. Systolic, diastolic, and mean blood pressures, intracellular free calcium
      concentration ([Ca2+]i), platelet serotonin (5-HT) contents, and aggregation were
      determined, at weeks 0, 2, and 7 of treatment. Inositol phosphates (InsP)
      production, platelet thromboxane A2 (TXA2) generation, and morphology of
      platelets, through electron microscopy studies, also were compared. It was
      demonstrated that blood pressures increased in the CsA-treated groups, when
      compared with the control group, after 2 and 7 weeks of administration. CsA at
      both "attack" and "maintenance" doses increased basal, 5-HT, and thrombin-evoked
      [Ca2+]i after 2 and 7 weeks versus the control group. However, basal and evoked
      InsP production was stimulated by 5 mg/kg of CsA, but inhibited by 30 mg/kg, when
      compared with the control. Platelet 5-HT contents decreased significantly after 2
      and 7 weeks in the CsA-treated groups, when compared with the control group.
      Collagen-induced whole blood platelet aggregation increased drastically in the
      "attack" CsA-treated group, whereas adenosine diphosphate (ADP)-induced platelet
      aggregation did not reach statistical significance. Finally, in vitro basal,
      collagen-, and ADP-evoked platelet TXA2 generation increased in both CsA
      concentrations, versus the control. In conclusion, our study demonstrates that
      both CsA doses alter platelet calcium homeostasis (even affecting the calcium
      fluxes differently), 5-HT and TXA2 contents and aggregation, which might
      contribute to the development and/or maintenance of high blood pressures and
      increased risk of thromboembolic complications.

PMID- 10892662
TI  - Ibudilast modulates platelet-endothelium interaction mainly through cyclic GMP
      dependent mechanism.
AB  - 3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (ibudilast) has been widely used
      in Japanese clinics for its antiasthmatic and antithrombotic effects. We
      investigated the mechanisms involved in the antiplatelet effects of the agent,
      specifically focusing on platelet-endothelium interaction. Ibudilast inhibits
      both phosphodiesterase (PDE) 3 and 5, the two major PDE isoforms of human
      platelets, with an IC50 of 31 and 2.2 microM, respectively. Cyclic guanosine
      monophosphate (GMP) accumulation in washed human platelets exposed to ibudilast
      alone increased significantly only at high concentrations of the agent (100
      microM), whereas > or = 1 microM ibudilast enhanced cyclic GMP levels in the
      platelets cocultured with bovine aorta endothelial cells (ECs). In contrast,
      ibudilast enhanced cyclic AMP accumulation only at 100 microM, either with or
      without ECs. The synergistic effect of ibudilast and EC on cyclic nucleotide
      accumulation also was demonstrated by the inhibitory capability of the drug and
      the cells on platelet aggregation. The synergism between ibudilast and aspirin
      pretreated ECs was more pronounced than that between ibudilast and N(omega)-nitro
      L-arginine (L-NNA)-pretreated ECs. Ibudilast affected neither ATP
      diphosphohydrolase activity nor NO release from EC up to a concentration of 10
      microM. We conclude that ibudilast exhibits antiplatelet properties mainly by
      inhibiting PDE5 to potentiate antiplatelet function of endothelium-derived NO.

PMID- 10892663
TI  - Effect of angiotensin II on aldosterone secretion in canine adrenal gland in
      situ.
AB  - To investigate the effect of angiotensin (ANG) II on aldosterone (ALDO)
      secretion, we measured arterial and adrenal venous plasma aldosterone
      concentrations in anesthetized dogs. The intraadrenal arterial infusion of ANG II
      (0.3 ng/kg/min) or potassium chloride (KCl) (0.6 mg/min) increased ALDO
      secretion. The changes in ALDO secretion in response to ANG II were tested during
      the concomitant arterial infusion of two graded doses of losartan (10 and 100
      ng/kg/min), PD 123319 (50 and 500 ng/kg/min), nifedipine (25 and 250 ng/kg/min),
      or TMB-8 (2 and 20 microg/kg/min). All of these test drugs except PD123319
      inhibited the ANG II-induced increase in ALDO secretion. Losartan did not affect
      the KCl-induced increase in ALDO secretion. These results indicate that ANG II
      acts on ANG II type 1 receptors in the adrenal gland and enhances ALDO secretion.
      They also suggest the involvement of both intracellular and extracellular calcium
      in the aldosterone response to stimulation by ANG II. Under these in vivo
      experimental conditions, the KCl-stimulated ALDO secretion does not appear to
      involve ANG II formation in the adrenal gland.

PMID- 10892664
TI  - Effects of a new class III antiarrhythmic drug nibentan in a canine model of
      vagally mediated atrial fibrillation.
AB  - Nibentan, a new class III antiarrhythmic drug, is highly effective in patients
      with atrial flutter and fibrillation. However, its mechanism of action remains
      unclear. The aim of this study was to investigate the effects of nibentan using a
      canine model of vagally sustained atrial fibrillation (AF). Nibentan was
      intravenously infused to anesthetized open-chest dogs during vagally induced AF.
      Cumulative doses of nibentan (0.063, 0.125, and 0.250 mg/kg) successfully
      terminated AF in 78, 88, and 100% as well as prevented AF reinduction in 11, 63,
      and 90% of cases, respectively. All doses of nibentan significantly and rate
      independently increased atrial effective refractory period (AERP) with and
      without vagal stimulation. Activation mapping (224 epicardial electrodes) during
      AF showed that nibentan reduced the number of simultaneously occurring reentrant
      wavelets. Herewith the atrial excitation slowed down until conduction failure of
      reentrant wavelets led to arrhythmia termination. These changes in activation
      patterns can be accounted for by nibentan-induced increase of AERP (55 +/- 9%, 82
      +/- 12%, and 90 +/- 6%; p < 0.01) and wavelength for reentry (47 +/- 7%, 68 +/-
      12%, and 72 +/- 4%; p < 0.01) at rapid atrial rates in the presence of vagal
      stimulation. In conclusion, the high efficacy of nibentan against AF was
      associated with significant rate-independent increase in AERP and in wavelength,
      and might be in part explained by block of both delayed rectifier (I(K)) and
      muscarinic I(K,ACh) currents.

PMID- 10892665
TI  - Intracoronary collagen: effects on coronary collateral circulation and the role
      of thromboxane.
AB  - This study investigated the effects of intravascular collagen on coronary
      collateral blood flow. Collateral vessel growth was stimulated in 11 dogs by
      embolizing the left anterior descending (LAD) coronary artery with a hollow
      stainless steel plug. Experiments were performed 41 +/- 7 days after coronary
      embolization when collateral vessels were moderately well developed. Under alpha
      chloralose anesthesia, the LAD was cannulated, and retrograde blood flow was used
      as a measure of collateral flow. Collagen (10-100 microg/kg) injected into the
      left main coronary artery caused a decrease of coronary collateral blood flow
      that became maximal at 3 min after injection and subsided within 9 min. At peak
      effect intracoronary collagen decreased retrograde flow by 53 +/- 6% from 32.7 +/
      8.2 to 16.8 +/- 3.7 ml/min (p < 0.05) with no change in systemic hemodynamics.
      Selective thromboxane A2 (TxA2)-receptor blockade with SQ30,741 had no effect on
      collateral blood flow during basal conditions but attenuated the collateral
      constriction in response to collagen. Thus, after SQ30,741, collagen caused only
      a nonsignificant decrease retrograde flow from 35.9 +/- 9.0 to 31.7 +/- 9.62
      ml/min. The findings indicate that intravascular collagen exerts a potent
      vasoconstrictor effect on coronary collateral vessels. Attenuation of this
      response by TxA2-receptor blockade suggests that thromboxane released by
      activated platelets is the principal mediator of this response.

PMID- 10892666
TI  - Differential effects of carvedilol on norepinephrine release in normoxic and
      ischemic heart.
AB  - Carvedilol is a beta-adrenoceptor antagonist with multiple actions, which may
      contribute to superior cardioprotection in heart failure and myocardial
      infarction. We hypothesized that carvedilol may modulate presynaptic
      norepinephrine release in the heart. Therefore, we compared the effects of
      carvedilol (racemate and both enantiomers) and beta1-selective as well as
      nonselective beta-adrenoceptor blockers on norepinephrine release in isolated
      perfused rat hearts under normoxic and brief ischemic conditions. Exocytotic
      release of endogenous norepinephrine was induced by paired electric field
      stimulations to compare the release before (S1) and after (S2) beta-adrenoceptor
      blocker application. Metoprolol, bisoprolol, and pindolol (0.1-10 microM) had
      essentially no effect on exocytotic norepinephrine release under normoxic and
      ischemic conditions. In contrast, carvedilol exerted a biphasic concentration
      response curve (increase followed by suppression) on norepinephrine release. The
      increase in norepinephrine release was more pronounced with R-carvedilol than
      with S-carvedilol, indicating an effect independent from beta-receptor
      antagonism. During ischemia, the facilitatory effect of carvedilol on
      norepinephrine release was lost, resulting in a concentration-dependent
      suppression of the release. These results indicate that carvedilol in contrast to
      classic beta1-selective and -nonselective beta-adrenoceptor blockers has
      pronounced effects on cardiac norepinephrine release with a remarkable difference
      between normoxic and ischemic conditions. Whereas a facilitation of
      norepinephrine release prevailed in normoxia, we observed a suppression of the
      release in ischemia. It remains to be established whether this unique action of
      carvedilol on cardiac sympathetic neurotransmission is of clinical relevance.

PMID- 10892667
TI  - Glibenclamide inhibits accumulation of cholesteryl ester in THP-1 human
      macrophages.
AB  - Glibenclamide is an adenosine triphosphate (ATP)-sensitive potassium channel
      inhibitor that is widely used in treating diabetes mellitus. However, the effects
      of this drug on cholesterol metabolism and atherogenesis are not well known. We
      investigated the effects of this agent on the cellular cholesterol metabolism in
      cultured human macrophages. The effect of glibenclamide was evaluated by the
      measurement of the cellular contents of total cholesterol, free cholesterol, and
      cholesteryl ester in the presence of low-density lipoprotein (LDL). The effect on
      the degradation and association of 125I-labeled LDL (125I-LDL) also were
      determined. Cholesterol efflux was measured in the absence and the presence of
      high-density lipoprotein (HDL). The secretion of apolipoprotein E also was
      determined. The synthesis and hydrolysis of cholesteryl ester were evaluated.
      Glibenclamide stimulated both synthesis and hydrolysis of cholesteryl ester, and
      inhibited the net accumulation of cholesteryl ester by LDL in a concentration
      dependent manner and even decreased its content compared with time 0 control.
      This drug had no effect on the degradation or association of 125I-LDL.
      Glibenclamide promoted the HDL-independent cholesterol efflux by decreasing
      esterified cholesterol and increasing the release of free cholesterol and
      secretion of apolipoprotein E into the medium. The other potassium channel
      inhibitors or openers had no effect on the cellular cholesterol levels. These
      results suggest that glibenclamide inhibits the accumulation of cholesteryl ester
      in macrophages by enhancing the hydrolysis of cholesteryl ester as well as by
      increasing cholesterol efflux, and possibly, by increasing the secretion of
      apolipoprotein E. These effects appeared to be unrelated to an effect on the
      potassium channel. Inhibition of accumulation of cellular cholesterol by
      glibenclamide might be favorable for the prevention of atherosclerotic disease.

PMID- 10892668
TI  - Evidence that prostaglandins mediate the antihypertensive actions of angiotensin
      (1-7) during chronic blockade of the renin-angiotensin system.
AB  - Prostaglandins are known to participate in the antihypertensive actions of
      angiotensin-converting enzyme (ACE) inhibition and angiotensin type 1 (AT1)
      receptor antagonism. Because angiotensin-(1-7) [Ang-(1-7)] is markedly elevated
      after prolonged ACE-inhibitor treatment, we determined whether the
      antihypertensive effects of Ang-(1-7) were mediated by release of prostaglandins.
      Male spontaneously hypertensive rats (SHRs, 10 weeks) were treated for 9 days
      with either lisinopril (20 mg/kg) or losartan (10 mg/kg) or a combination of both
      drugs. Rats were implanted with catheters in the carotid artery and jugular vein
      to record blood pressure and to infuse drug solutions, respectively.
      Neutralization of circulating Ang-(1-7) by monoclonal antibody resulted in a dose
      dependent increase in blood pressure in SHRs treated with either lisinopril or
      losartan. Administration of CGS 24592 to block Ang-(1-7) formation also resulted
      in an increase in blood pressure that was comparable to antibody infusion.
      However, Ang-(1-7) blockade evoked a greater elevation in blood pressure in the
      lisinopril and lisinopril/losartan-treated rats in comparison to those treated
      with losartan alone. Acute treatment with the cyclooxygenase (COX) inhibitor
      indomethacin increased blood pressure to a similar extent to that of CGS 24592,
      as well as blocked the increase in pressure with the neprilysin inhibitor in the
      lisinopril/losartan group. In the losartan-treated animals, however, indomethacin
      increased blood pressure by a larger extent than that of the Ang-(1-7) antibody
      or CGS 24592, and CGS 24592 did not abolish the subsequent pressor response to
      indomethacin in these animals. In contrast to the antibody or neprilysin
      inhibitor, administration of the Ang-(1-7) antagonist D-[Ala7]-Ang-(1-7)
      increased blood pressure to a similar extent in lisinopril or losartan
      treatments. Moreover, D-[Ala7]-Ang-(1-7) increased blood pressure to a comparable
      extent as indomethacin and blocked any further increase with the COX inhibitor in
      the losartan-treated SHRs. High-resolution emulsion autoradiography revealed 125I
      [Sarcosine1, Threonine8]-Ang II (Sarthran) binding in the mesenteric artery and
      thoracic aorta in the presence of both LOS and the AT2 antagonist PD123319. The
      non-AT1/non-AT2 Sarthran binding was displaced by Ang-(1-7), DALA, or Ang II.
      These studies suggest that vasodilatory eicosanoids mediate the antihypertensive
      effects of endogenous Ang-(1-7) in both LIS and LIS/LOS therapies. Furthermore,
      in the presence of AT1-receptor blockade, Ang II may interact with a DALA
      sensitive site to promote eicosanoid release.

PMID- 10892669
TI  - Effects of OR-1896, an active metabolite of levosimendan, on contractile force
      and aequorin light transients in intact rabbit ventricular myocardium.
AB  - We performed experiments in rabbit ventricular papillary muscles loaded with
      aequorin to elucidate the mechanism of positive inotropic effect (PIE) of OR
      1896, an active metabolite of levosimendan. The concentration-response curve
      (CRC) for OR-1896 was biphasic: PIE of OR-1896 reached a plateau at 10(-5) M
      (first phase), and the CRC became steeper at 10(-3) M and higher (second phase).
      Maximal response of the first phase was 11% of the maximal response to
      isoproterenol (ISOmax) and associated with an increase in Ca2+ transients of 5%
      of ISOmax. For a given degree of PIE, the increase in Ca2+ transients by OR-1896
      was lower than that induced by elevation of [Ca2+]o. The PIE of OR-1896 was not
      associated with impairment of relaxation, and it was abolished by carbachol. In
      conclusion, OR-1896 has a PIE partly due to an increase in myofibrillar Ca2+
      sensitivity that is exerted through crosstalk with signal transduction mediated
      by cyclic adenosine monophosphate (cAMP).

PMID- 10892670
TI  - Impact of beta-adrenoceptor antagonists on myofilament calcium sensitivity of
      rabbit and human myocardium.
AB  - Beta-adrenoceptor antagonists (beta-blockers) are commonly used in clinical
      pharmacotherapy of cardiovascular diseases. Carvedilol and nebivolol possess
      beneficial effects on myocardial function in situations of oxidative stress
      associated with intracellular calcium overload. This preservation of contractile
      function might be due to direct scavenging capacities or to compensation of the
      intracellular calcium overload through direct impact on myofilament calcium
      sensitivity. Accordingly, we measured the relation between calcium and force in
      the absence and in the presence of 10(-6) M carvedilol, nebivolol, or propranolol
      in skinned right ventricular trabeculae of rabbit hearts. In rabbit myocardium,
      nebivolol (10(-6) M) altered the pCa50% by a rightward shift (less sensitive)
      from 5.72 +/- 0.05 to 5.57 +/- 0.05 (p < 0.05). Maximal force development was
      reduced by nebivolol. In contrast, the same concentration of propranolol or
      carvedilol did not influence calcium sensitivity and force development. In
      additional experiments, we repeated this protocol in trabeculae from human
      failing hearts. As in rabbit trabeculae, nebivolol shifted the pCa50% by 0.16 +/-
      0.04 pCa units to the right (p < 0.05). Experiments with intact rabbit trabeculae
      confirmed depressed contractility: when all beta-adrenoceptors were blocked by
      10(-6) M propranolol, subsequent addition of 10(-6) M nebivolol reduced developed
      force of these muscles significantly from 3.1 +/- 0.9 to 1.7 +/- 0.4 mN/mm2. We
      conclude that nebivolol desensitizes cardiac myofilaments slightly, whereas
      neither propranolol nor carvedilol had an effect.

PMID- 10892671
TI  - Are there sex-specific differences in ventricular repolarization or in drug
      induced early afterdepolarizations in isolated rabbit purkinje fibers?
AB  - Women are known to have a longer QT interval than men and a greater propensity
      toward drug-induced "torsades de pointes" (TdPs). However, little is known about
      these sex differences in isolated cardiac tissues. We evaluated potential sex
      differences in repolarization in isolated rabbit Purkinje fibers using a
      microelectrode technique. Isolated male or female Purkinje fibers were perfused
      in a Tyrode's solution with solvent, dofetilide (1 x 10(-8) M) or quinidine (1 x
      10(-5) M), and stimulated at 1 or 0.2 Hz. Female Purkinje fibers with solvent (n
      = 11) tended to have a longer duration of the action potential at 90%
      repolarization (APD90) than male fibers with solvent (n = 10): 331 (median) vs.
      272 ms at 1 Hz (p > 0.05); 473 vs. 367 ms at 0.2 Hz (p < 0.05). Dofetilide (1 x
      10(-8) M) significantly increased APD90 more in female Purkinje fibers (n = 11)
      than in male fibers (n = 10): 670 vs. 385 ms at 1 Hz, at 20 min after the
      infusion (p < 0.05), and 1,000 vs. 937 ms at 0.2 Hz at the end of the 25-min
      infusion (p < 0.05), respectively. Quinidine (1 x 10(-5) M) tended to increase
      APD90 more in female Purkinje fibers (n = 11) than in male fibers (n = 10): 705
      vs. 500 ms at 1 Hz, at 20 min after the infusion (p > 0.05). Furthermore,
      dofetilide (1 x 10(-8) M) and quinidine (1 x 10(-5) M) elicited a higher
      incidence of early afterdepolarizations in female Purkinje fibers than in male
      fibers at 0.2 Hz (100 vs. 60%, p < 0.05; and 91 vs. 50%, p > 0.05). Our data
      indicate that female Purkinje fibers tend to have longer ventricular
      repolarization and are at higher risk of drug-induced early afterdepolarizations
      at a slow stimulation rate than male fibers. This may contribute to a sex
      difference in QT interval and to a greater tendency on the part of women to the
      development of drug-induced TdPs.

PMID- 10892672
TI  - Chronic sinusitis and anosmia: pathologic changes in the olfactory mucosa.
AB  - OBJECTIVES: To evaluate histological changes in the olfactory mucosa of patients
      with chronic rhinosinusitis These results are analyzed in light of current
      understanding of the pathophysiology of anosmia secondary to nasal and sinus
      disease. STUDY DESIGN: Prospective study of olfaction on patients undergoing
      sinus surgery for the management of chronic rhinosinusitis. METHODS: Thirty
      patients, aged 22 to 39 years, underwent olfactory biopsy at the time of surgery
      with evaluation by a pathologist. Inflammatory changes were graded as mild
      (normal), moderate, or severe. Clinical olfactory function was evaluated using
      the University of Pennsylvania Smell Identification Test (UPSIT). The results
      correlated with the degree of olfactory dysfunction. RESULTS: Of the 30 patients
      19 had unequivocal olfactory mucosa in the biopsy specimen. Eleven had only
      respiratory or indeterminate mucosa. Nine patients demonstrated normal olfactory
      mucosa and normal olfactory function (UPSIT > 35). Ten patients demonstrated
      pathological changes in the olfactory mucosa with an influx of lymphocytes,
      macrophages, and eosinophils Of these 10 patients, 7 had olfactory deficits as
      determined by UPSIT. The remaining three patients had normal olfactory function
      despite moderate chronic inflammation. These studies indicate that the olfactory
      mucosa is capable of mounting an inflammatory response similar to that seen in
      the respiratory mucosa of patients with chronic sinusitis These data suggest that
      the olfactory deficits in these patients may be the result of inflammatory
      changes within the olfactory mucosa in addition to any alteration in airflow to
      the olfactory cleft.

PMID- 10892673
TI  - The "case" of Joseph Haydn: a rhinological patient during the eighteenth century.

PMID- 10892674
TI  - Airway compromise in thyroplasty surgery.
AB  - OBJECTIVES: Airway compromise arising from thyroplasty procedures including
      Isshiki type I through IV thyroplasties, arytenoid adduction, and arytenoid
      fixation is uncommon yet potentially life threatening. Identification of
      incidence of obstruction and probable causes is important for preoperative
      planning, consultation, and postoperative care. STUDY DESIGN: Retrospective
      review of all thyroplasty operations, including arytenoid adduction and arytenoid
      fixation. METHODS: Three hundred thirty-two patients underwent a total of 630
      thyroplasty procedures. Detailed information was gathered on patients manifesting
      symptoms of airway obstruction. RESULTS: Seven patients required an unplanned
      tracheostomy for airway compromise. Five of 143 patients who underwent arytenoid
      adduction required a tracheostomy, for an incidence of 3.5%. The median interval
      to developing significant stridor requiring tracheostomy was 9 hours, with five
      of these seven patients requiring airway surgery within the first 18
      postoperative hours. No patient receiving a type I thyroplasty alone developed
      significant airway compromise. Tracheostomy was required in two patients with
      underlying neuromuscular disease-one who underwent a bilateral type I thyroplasty
      and one who underwent an arytenoid fixation procedure. CONCLUSION: The percentage
      of airway complications after thyroplasty is low. However, arytenoid adduction
      and fixation operations have a significant risk of postoperative temporary
      tracheostomy and warrant preoperative discussion regarding tracheostomy and
      postoperative overnight hospital admission.

PMID- 10892675
TI  - Effects of thyroplasty type I on vocal fold vibration.
AB  - OBJECTIVE: To ascertain effects of medialization thyroplasty on vocal fold
      vibration in glottic incompetence dysphonia. STUDY DESIGN: Quantitative
      videostroboscopic glottic measurements and vocal function study were
      perioperatively undertaken in 20 patients undergoing Isshiki's thyroplasty type
      I. METHODS: In digitized images, the glottal area, glottal width, posterior
      glottal width, and amplitude over an entire glottal cycle were measured and
      normalized by membranous vocal fold length. The ratio of closed phase to total
      phase of vibratory cycle was calculated from the data of the glottal area and the
      glottal width at the middle point of the membranous vocal fold. Well-accepted
      acoustic, aerodynamic, and perceptual measures analyzed vocal function. RESULTS:
      Glottal area and glottal width were reduced after surgery. While preoperative
      closure of glottal area was incomplete in all 20 patients, incomplete closure was
      obtained in 16 patients after surgery. In these 16 patients, closure of glottal
      width at the middle point of the membranous vocal fold was complete, whereas a
      posterior glottal gap remained in 14 patients. Closed phase over one cycle of
      glottal width waveform and amplitude of vocal fold vibration were increased after
      surgery. Glottal area, glottal width, posterior glottal width, and closed phase
      over one cycle of glottal width waveform correlated with vocal function measures.
      CONCLUSIONS: Thyroplasty type I reduces a glottal gap and increases closed phase
      over one cycle and amplitude of vocal fold vibration, although a posterior
      glottal gap remains. With the improved glottic vibration, thyroplasty type I
      provides more efficient phonation in patients with glottic incompetence
      dysphonia.

PMID- 10892676
TI  - Radiofrequency volumetric tissue reduction of the soft palate: a new treatment
      for snoring.
AB  - OBJECTIVE/HYPOTHESIS: Current options for the treatment of snoring have limited
      acceptance because of intolerance, expense, pain, or need for general anesthesia.
      A clinical trial using a new application of a previously known technology
      radiofrequency energy-was investigated to determine its efficacy in the treatment
      of snoring. Effects of treatment on speech, swallowing, pain, snoring, and degree
      of sleepiness were evaluated. These effects were evaluated by post-treatment
      questionnaires. METHODS: Prospective nonrandomized study. All included subjects
      snored at a level considered bothersome to their bed partner. A total of 43
      patients were enrolled at the University of Maryland (UM) and the Georgia Ear
      Institute (GEI). Polysomnography was performed before treatment to eliminate
      patients with significant sleep apnea who had respiratory disturbance indices
      (RDIs) greater than 15 or nadir desaturations less than 80%. The mean
      pretreatment RDI for all patients who entered the protocol at UM was 6.7 +/- 4.7.
      Nine patients completed the study in this group in all other aspects, but did not
      return for their scheduled post-treatment polysomnogram. At GEI, pretreatment
      polysomnograms revealed a mean RDI of 8.9 +/- 3.8. Eleven patients at GEI
      completed the study in all other aspects but did not return for their scheduled
      post-treatment polysomnogram. Radiofrequency energy was delivered to the soft
      palate either in the midline (19 patients) at a mean of 698 +/- 52 J per
      treatment at UM or in the midline and lateral soft palate (24 patients) at a mean
      of 1,254 +/- 191 J per treatment at GEI. At UM the mean age was 44.3 +/- 8.4
      years, with a range from 29 to 59 years. Eighty-four percent of the patients were
      men. The mean body mass index (BMI) was 28.5 +/- 3.2. Twenty-four patients were
      enrolled at GEI. The mean age was 44.0 +/- 10.9 years, with a range from 23 to 63
      years. Seventy-four percent of patients were men. The mean BMI was 27.7 +/- 3.8.
      Snoring, pain, swallowing, and speech were assessed after each treatment at post
      treatment day 1, 2, or 3; week 1; week 4; and week 7. Daytime sleepiness was
      assessed by the Epworth Sleepiness Scores (ESS) obtained at the same intervals.
      RESULTS: Snoring was improved in 77% of patients after three treatments or less.
      Seventy-nine percent of patients treated with the midline technique at UM and 96%
      of patients treated with the midline and left and right lateral palate technique
      at GEI achieved an improvement in their snoring to a level that was no longer
      bothersome to their bed partner. No persistent negative impact was noted
      concerning speech or swallowing. Improvements in degree of sleepiness were
      observed by comparing pretreatment and post-treatment ESS. ESS was significantly
      reduced (P < .005) after treatment from 10.2 +/- 6.1 to 6.1 +/- 4.7 at UM, and at
      the GEI, from 8.75 +/- 4.4 to 5.3 +/- 3.2. After a treatment, 27% of the patients
      at UM and 29% at GEI required analgesics. CONCLUSIONS: This clinical trial
      demonstrates the efficacy, safety, and lack of pain encountered when using
      radiofrequency energy delivered to the palate for the treatment of snoring. The
      tolerability, lack of pain, and ability to perform the procedure with the patient
      under local anesthesia in the office make the use of this technology an excellent
      option for the treatment of snoring.

PMID- 10892677
TI  - Pediatric tracheotomies: changing indications and outcomes.
AB  - OBJECTIVE/HYPOTHESIS: To study the outcomes and complications associated with
      pediatric tracheotomy, as well as the changing trend in indications and outcomes
      since 1970. STUDY DESIGN: Retrospective chart review at a major tertiary care
      children's hospital. METHODS: On children who underwent tracheotomy at Children's
      Hospital of the King's Daughters (Norfolk, VA) between 1988 and 1998, inpatient
      and outpatient records were reviewed. Of 218 tracheotomies, sufficient data were
      available on 204. Indications for tracheotomy were placed into the following six
      groups: craniofacial abnormalities (13%), upper airway obstruction (19%),
      prolonged intubation (26%), neurological impairment (27%), trauma (7%), and vocal
      fold paralysis (7%). RESULTS: The average age at tracheotomy was 3.2 +/- 0.6
      years. Although the prolonged intubation group was significantly younger than all
      others, the neurological impairment and trauma groups were significantly older.
      Decannulation was accomplished in 41%. Time to decannulation was significantly
      higher in the neurological impairment and prolonged intubation groups, but was
      significantly shorter in the craniofacial group. Complications occurred in 44%.
      Overall mortality was 19%, with a 3.6% tracheotomy-related death rate. Comparison
      of our series to other published series of pediatric tracheotomies since 1970
      shows fewer being performed for airway infections and more for chronic diseases,
      with a corresponding increase in duration of tracheotomy and decreased
      decannulation rates. CONCLUSIONS: Tracheotomy is a procedure performed with
      relative frequency at tertiary care children's hospitals. While children
      receiving a tracheotomy have a high overall mortality, deaths are usually related
      to the underlying disease, not the tracheotomy itself.

PMID- 10892678
TI  - Transcranial magnetic stimulation in acute facial nerve injury.
AB  - OBJECTIVE/HYPOTHESIS: Available electrodiagnostic tests that are used to evaluate
      facial nerve injury examine the nerve distal to the stylomastoid foramen; because
      most facial nerve injuries are within the temporal bone, the tests cannot
      evaluate the nerve at or across the injury site. The interpretation of these
      tests depends on the predictability (or unpredictability) of distal degenerative
      process. Transcranial magnetic stimulation may be able to stimulate the nerve
      proximal to the injury site. The hypothesis of the present study is that in cases
      of mild traumatic facial nerve injury where axonal integrity is maintained,
      proximal stimulation of the nerve using higher than normal stimulus intensities
      to "overcome" the block at the injury site result in recordable facial nerve
      activity. STUDY DESIGN: A prospective controlled animal study comparing response
      to transcranial magnetic stimulation of the facial nerve in the following groups:
      mild injury, severe injury/transection, and control. METHODS: We studied 44
      facial nerves in 22 cats. Fifteen nerves were subjected to mild trauma. Five
      nerves were severely crushed, 2 nerves were completely transected, and 22 nerves
      were not traumatized. All nerves were examined with the transcranial magnetic
      stimulation system before the trauma, immediately after the trauma, and at 3, 8,
      and 12 weeks after trauma. RESULTS: All nerves in the mild and severe trauma
      groups showed complete clinical paralysis immediately after trauma. The nerves in
      the mild trauma group showed significant increase in threshold as well as
      significant increase in latency for recordable facial muscle response to
      transcranial magnetic stimulation. Thresholds and latencies decreased gradually
      within 3 to 12 weeks and returned almost to preinjury levels. This paralleled the
      return of clinical facial muscle movement. In the severe trauma/transection
      group, the nerves had no facial muscle response to transcranial magnetic
      stimulation after trauma. Neither facial muscle response to transcranial magnetic
      stimulation nor facial muscle movements recovered. CONCLUSIONS: In cats
      transcranial magnetic stimulation can assess the integrity of the facial nerve
      after trauma and predict its potential for regeneration. This technique can
      excite the nerve proximal to the injury site and may play a role in the clinical
      evaluation of the acute traumatic facial nerve paralysis. It can be used
      immediately after trauma, because it does not depend on wallerian degeneration to
      occur.

PMID- 10892679
TI  - An animal model for external ear canal inflammation.
AB  - OBJECTIVE: To develop an animal model for testing efficacy of anti-inflammatory
      drugs designed to treat external ear canal (EAC) disease. METHODS: Histological
      and morphometric methods were used to characterize EAC inflammation produced by
      topical application of tetradecanoylphorbol acetate (TPA) in mice. The effects of
      both single and repeated TPA applications were studied. A treatment trial was
      performed to evaluate the effects of a ciprofloxacin/hydrocortisone suspension on
      TPA-induced EAC inflammation. In 10 animals, two bilateral applications of TPA
      were made, spaced 24 hours apart. Immediately after the second TPA application,
      otic suspension was applied unilaterally four times over a 48-hour period. The
      contralateral EACs were left untreated to provide TPA-only controls. RESULTS:
      Twenty-four hours after a single TPA application, EAC skin showed
      polymorphonuclear (PMN) leukocyte infiltration, vascular dilation, and thickening
      of the dermis and epidermis. Dermal and epidermal thickening were more pronounced
      after two TPA applications and PMN leukocyte infiltration remained high 48 hours
      after a second TPA placement. After treatment with the otic suspension, PMN
      leukocyte counts were reduced by an average of 76% relative to EACs that received
      TPA only. There was also statistically significant reduction of dermal swelling
      and a trend toward reduced epidermal thickness. Vascular dilation was clearly
      reduced as well EACs that received four applications of the suspension alone
      showed no adverse effects compared with those that received saline. CONCLUSION:
      TPA-induced inflammation of the mouse EAC provides a suitable model for testing
      the therapeutic efficacy of anti-inflammatory agents being considered for
      clinical use.

PMID- 10892680
TI  - Noninvasive fluorescent identification of bacteria causing acute otitis media in
      a chinchilla model.
AB  - OBJECTIVES: To evaluate a noninvasive method of bacterial identification via
      fluorescence spectroscopy in the setting of acute otitis media in a chinchilla
      model. STUDY DESIGN: Prospective. METHODS: For each chinchilla, transbullar
      inoculation with Streptococcus pneumoniae, Haemophilus influenzae, or
      Staphylococcus aureus was performed bilaterally and clinical infection was
      determined by otoscopy. An optical fiber coupled to a spectrofluorometer allowed
      for the delivery of an excitation wavelength to the inflamed tympanic membrane
      and the acquisition of the resulting emission signal. Sequential emission spectra
      obtained over a range of excitation wavelengths were assembled by a computer
      algorithm, and a single, three-dimensional plot was created for each test ear.
      Similarly, plots from the healthy external auditory canal (EAC) were also
      recorded. Twelve animals were used to establish a library of four reference plots
      representing the three bacteria and the EAC. Of the 24 ears available for study,
      10 were excluded from analysis because of lack of clinical infection or presence
      of tympanic membrane perforation with purulent drainage. From four additional
      animals, four samples from ears infected with the above bacteria and three
      samples of the EAC served as unknowns. The unknown plots were analyzed by an
      investigator blinded to their identity. RESULTS: Using a multiple correlation of
      the unknown to the reference plots, seven of seven samples were correctly
      identified. CONCLUSIONS: We were able to establish a prototype method for the
      noninvasive identification of a limited library of pathogens in a chinchilla
      model of acute otitis media.

PMID- 10892681
TI  - Controlling advanced neck disease: efficacy of neck dissection and radiotherapy.
AB  - OBJECTIVE: Neck dissection remains the standard method of treating cervical
      metastasis from head and neck squamous cell carcinoma. In light of recent trends
      to modify the classic radical neck dissection (RND) for early neck disease, we
      reviewed our experience with radical and modified RND (MRND) plus radiotherapy as
      treatment for N2/N3 neck disease in head and neck squamous cell carcinoma.
      METHODS: We retrospectively reviewed our clinical records from July 1989 to June
      1996 to identify 43 neck dissections in 39 patients who were found to have
      pathologically N2 or N3 neck disease treated primarily by neck dissection and
      postoperative radiotherapy. All patients had head and neck squamous cell
      carcinoma with a minimum follow-up of 24 months. RESULTS: Nine percent (4/43) of
      the dissected necks were pathologically N2a, 72% (31/43) were N2b, 7% (3/43) were
      N2c, and 12% (5/43) were N3. Of these, 28% (12/43) underwent a RND and 72%
      (31/43) underwent a MRND. The most common modification of RND was preservation of
      the spinal accessory nerve. All patients underwent postoperative radiotherapy
      with a mean dose of 55 Gy. Only 4 of 43 dissected necks had isolated treatment
      failure, for a regional control rate of 91%. CONCLUSIONS: The combination of RND
      or MRND and radiotherapy is highly effective in controlling neck disease in the
      absence of persistent or recurrent local disease. Also, in our experience, MRND
      appears to be as effective as RND in controlling even advanced neck disease,
      which supports preservation of the spinal accessory nerve whenever oncologically
      feasible.

PMID- 10892682
TI  - Reducing post-tonsillectomy pain with cryoanalgesia: a randomized controlled
      trial.
AB  - OBJECTIVE/HYPOTHESIS: To evaluate the use of cryoanalgesia in reducing post
      tonsillectomy pain. STUDY DESIGN: A prospective, randomized double-blind study of
      59 consecutive patients (age range, 8-40 y) undergoing tonsillectomy for
      recurrent tonsillitis. METHODS: All patients underwent bipolar tonsillectomy. At
      the completion of the tonsillectomy patients were randomly assigned to a control
      or a cryotherapy group. The cryotherapy patients had both their tonsillar fossa
      "supercooled" to between -20 degrees C and -32 degrees C for 1 minute. Patients
      recorded their pain using a visual analogue scale over the next 10 days. Patients
      were also monitored for postoperative complications, time until resumption of a
      normal diet, time back to work or school, and analgesic consumption. RESULTS: The
      two groups were similar for age and sex. There was a 28.3% reduction in mean pain
      scores over the 10 days in the cryotherapy compared to the control group. This
      difference did not significantly depend on the day after operation or time of the
      day. Cryotherapy patients also returned to work or school, on average, 4 days
      earlier than controls. There was no significant difference in postoperative
      complications between the two groups. CONCLUSION: Cryotherapy is a new technique
      that significantly reduces post-tonsillectomy pain without evidence of causing
      additional complications.

PMID- 10892683
TI  - Fiberoptic endoscopic evaluation of swallowing in the pediatric population.
AB  - OBJECTIVE: To investigate the diagnostic and rehabilitative usefulness of routine
      fiberoptic endoscopic evaluation of swallowing (FEES) in the pediatric
      population. STUDY DESIGN: Prospective, consecutive, blinded. PATIENTS AND
      METHODS: Thirty pediatric inpatients from a large, urban, tertiary care teaching
      hospital participated. Their ages ranged from 11 days to 20 years (mean, 10 years
      and 4 months). In a random fashion, seven subjects were assessed with both
      videofluoroscopic evaluation of swallowing (VFES) and FEES and 23 subjects were
      assessed solely with FEES. Diagnosis of dysphagia was determined by spillage,
      residue, laryngeal penetration, and aspiration. Rehabilitative strategies, e.g.,
      positioning and modification of bolus consistencies, were based on diagnostic
      findings. RESULTS: There was 100% agreement between the blinded diagnostic
      results and implementation of rehabilitative strategies for subjects randomly
      assigned to receive both VFES and FEES and for subjects who received solely FEES.
      Of the 23 subjects assessed solely with FEES, 13 of 23 (57%) exhibited normal
      swallowing and 10 of 23 (43%) exhibited dysphagia. The feeding recommendation for
      4 of 10 subjects with dysphagia (40%) was for a non-oral diet because of
      aspiration. FEES allowed for specific feeding recommendations (i.e., bolus
      consistency modifications, positioning, and feeding strategies) to reduce
      aspiration risk in 6 of 10 subjects with dysphagia (60%). CONCLUSION: FEES can be
      used routinely to diagnose and treat pediatric dysphagia in the acute care
      setting.

PMID- 10892684
TI  - Postsurgical prevertebral abscess of the cervical spine.
AB  - OBJECTIVES: Prevertebral abscess formation is an uncommon occurrence following
      cervical spine fusion surgery. Abscesses may present early or in a delayed
      fashion and require surgical drainage and long-term antibiotic treatment. The
      issues of osteomyelitis and the need for plate removal remain unresolved. STUDY
      DESIGN: A case series of six tetraplegic patients admitted for rehabilitation to
      the Chaim Sheba Medical Center (Tel Hashomer, Israel) is presented. METHODS: Five
      patients were trauma patients; one patient underwent repeated procedures and
      irradiation for tumor of the cervical spine. All patients developed prevertebral
      abscesses after a mean period of 30 days from their fusion surgery. Computed
      tomography scan was used in all patients to establish the diagnosis and define
      the extent of the infective process. All patients underwent one or more drainage
      procedures. The plate was removed in two patients at 1 and 4 months. RESULTS:
      Infection completely resolved in four patient and was refractory in one patient
      with malignant tumor, and a chronic small fistula remained in one case.
      Staphylococcus aureus was the main infective organism, but mixed infections were
      the rule. Even for a protracted course of infection, no significant osteomyelitis
      was encountered. CONCLUSIONS: Abscess formation after instrumentation of the neck
      may be more common than formerly recognized. Despite the prolonged course of
      disease and treatment, osteomyelitis is not a major concern. There is no
      automatic indication for plate removal to control infection, although plating may
      be safely removed after 10 to 12 weeks if the neck is explored and the cervical
      spine is stable. A high index of suspicion is warranted, and early recognition
      and diagnosis, prompt surgical drainage under general anesthesia, and long-term
      antibiotic treatment are key for eradication of the infective process.
      Prophylactic antibiotics may be of value. Meticulous antisepsis and surgical
      technique should be maintained to reduce the incidence of these severe
      complications.

PMID- 10892685
TI  - Endoscopically monitored percutaneous dilational tracheotomy in a residency
      program.
AB  - OBJECTIVES/HYPOTHESIS: Endoscopically guided percutaneous dilational tracheotomy
      (PDT) has become a well-established alternative to the more traditional open
      tracheotomy, yet its use by otolaryngologists is limited. As airway management
      specialists, otolaryngologists should be familiar with a wide range of definitive
      procedures, including PDT. Few otolaryngology programs teach the technique. The
      objective of the present study was to determine the complication rate and outcome
      of PDT after its introduction in a residency teaching program. We also wished to
      evaluate whether the time savings reported by experienced surgeons could be
      repeated in our setting. SETTING: Tertiary referral teaching hospital. METHODS:
      We prospectively reviewed our first 54 consecutive PDTs and compared them to 29
      consecutive standard open tracheotomies, which were reviewed retrospectively.
      RESULTS: Complications (13% vs. 33%, P = .030), operative time (12 vs. 24 min, P
      < .0001) and total procedure time (37 vs. 80 min, P < .001) were significantly
      reduced in the PDT group as compared with standard tracheotomy. Initial outcome
      data were equal in both groups. CONCLUSIONS: We found that PDT can be safely and
      effectively taught as part of an otolaryngology residency training program.

PMID- 10892686
TI  - The larynx during exercise.
AB  - OBJECTIVES: To develop a system capable of observing the larynx during various
      body movements and to investigate the relation between upper limb movements and
      laryngeal closure, often referred as "airtrapping." STUDY DESIGN: An endoscope
      capable of observing the larynx during various body movements was developed and
      the laryngeal state was monitored during these movements in three subjects. The
      output of 12 subjects' forearms was recorded with and without laryngeal closure.
      RESULTS: The larynx was observable even during extreme exercises such as
      horizontal bar exercises and vault exercises. Laryngeal closure was almost always
      seen during the beginning of maximum effort of the upper limbs. During constant
      effort, the state of the larynx varied. When the output of the upper limbs was
      compared with and without laryngeal closure, there was an average of 20% power
      loss. CONCLUSIONS: This study suggests four possible uses for this system. 1) The
      system could be useful to evaluate laryngeal disorders during exercise such as
      exercise-induced laryngomalacia. 2) The results could be used to improve the
      pushing exercise, a voice therapy technique. 3) The status of patients with
      incomplete laryngeal closure in connection with the upper limbs could be
      evaluated more thoroughly. 4) The technique and equipment could be used to
      observe the larynges during normal vocal processes that require body movement.

PMID- 10892687
TI  - Efficacy of botulinum toxin A for treatment of upper esophageal sphincter
      dysfunction.
AB  - OBJECTIVES: To investigate the efficacy of botulinum toxin A (BTA)-induced
      chemodenervation of the upper esophageal sphincter (UES) in patients with
      dysphagia and UES dysfunction. STUDY DESIGN: Prospective clinical trial in 10
      selected patients with pure UES dysfunction. METHODS: In each patient 30 units of
      BTA were injected into the UES under brief general anesthesia. Videofluoroscopic
      swallowing study (VSS) was done and a clinical symptom score was determined
      before and after treatment. RESULTS: On VSS relative opening of the UES improved
      in all patients (mean +/- SD: 47 +/- 14% before versus 71 +/- 24% after
      treatment; P < .01). Hypopharyngeal retention or laryngeal penetration of barium
      was significantly reduced in four of seven patients. Clinical symptom scores
      improved in all patients. One patient was free of symptoms, mild dysphagia
      persisted in six patients, and moderate dysphagia persisted in three patients.
      CONCLUSIONS: Our results support the use of BTA in selected patients with pure
      UES dysfunction. Its efficacy is limited by the possibility of a persistent
      structural stenosis of the UES and the risk of BTA diffusion into the larynx or
      hypopharynx.

PMID- 10892688
TI  - Acoustic characteristics of voice after severe traumatic brain injury.
AB  - OBJECTIVES/HYPOTHESIS: To describe the acoustic characteristics of voice in
      individuals with motor speech disorders after traumatic brain injury (TBI). STUDY
      DESIGN: Prospective study of 100 individuals with TBI based on consecutive
      referrals for motor speech evaluations. METHODS: Subjects were audio tape
      recorded while producing sustained vowels and single word and sentence
      intelligibility tests. Laryngeal airway resistance was estimated, and voice
      quality was rated perceptually. RESULTS: None of the subjects evidenced vocal
      parameters within normal limits. The most frequently occurring abnormal parameter
      across subjects was amplitude perturbation, followed by voice turbulence index.
      Twenty-three percent of subjects evidenced deviation in all five parameters
      measured. The perceptual ratings of breathiness were significantly correlated
      with both the amplitude perturbation quotient and the noise-to-harmonics ratio.
      CONCLUSIONS: Vocal quality deviation is common in motor speech disorders after
      TBI and may impact intelligibility.

PMID- 10892689
TI  - Endoscopic management of skull base osteoradionecrosis.
AB  - OBJECTIVE: Osteoradionecrosis is one of the most serious complications in
      radiotherapy of nasopharyngeal carcinoma. We describe a new endoscopic approach
      to resolve resultant skull base osteoradionecrosis. The objective of this study
      is to evaluate the efficacy of endoscopic management of skull base
      osteoradionecrosis. STUDY DESIGN: A prospective study of the outcome of
      endoscopic management for patients with skull base osteoradionecrosis. METHODS:
      Between 1994 and 1998 six patients who had irradiation previously for
      nasopharyngeal carcinoma had skull base osteoradionecrosis. A sinoscopic approach
      was applied for diagnosis and sequestrectomy. This diagnosis was based on the
      criterion of exposed necrotic bone after removing all crust in the nasopharynx
      and further confirmed on pathological examination after sequestrectomy. Effective
      cure was defined as intact mucosal coverage without any ulcer or exposed necrotic
      bone observed in the nasopharynx and the absence of antecedent accompanying
      symptoms after management. RESULTS: Six patients (10%) were symptom free. Five
      (83.3%) patients had effective cure. There was no surgical morbidity or
      mortality. CONCLUSION: Endoscopic sequestrectomy is a justified approach to skull
      base osteoradionecrosis.

PMID- 10892690
TI  - Transnasal endoscopic repair of cerebrospinal fluid rhinorrhea: a meta-analysis.
AB  - OBJECTIVES/HYPOTHESIS: Trauma and surgery are the most common causes of
      cerebrospinal fluid (CSF) rhinorrhea. Surgical repair is recommended for patients
      with CSF leaks that do not respond to conservative measures, traumatic CSF leaks
      that require transcranial surgery for associated brain injuries, and iatrogenic
      defects that are discovered intraoperatively. The purpose of our study was to
      ascertain the outcome after transnasal endoscopic repair of CSF leaks and to
      identify factors regarding the patient, CSF fistula, and treatment that may
      influence the results of the repair. METHODS: We performed a meta-analysis of all
      studies published in English between 1990 and 1999 that reported a minimum of
      five patients with CSF fistulae that were repaired using an endoscopic approach.
      We analyzed data that included type of graft and technique used during the
      repair, surgical complications, the use of packing, and the use of lumbar drains
      and antibiotics. The success rate was monitored and correlated with the other
      variables. The meta-analysis database was compared with and added to a database
      comprising our own patients. RESULTS: Fourteen studies comprising 289 CSF
      fistulae met the inclusion criteria. Endoscopic repair of CSF leaks was
      successful in 90% (259/289) of the cases after a first attempt. Seventeen of 30
      persistent leaks (52%) were closed after a second attempt. Thus ultimately 97%
      (276/289) of the leaks were repaired using an endoscopic approach. The success
      rate of repairs using any of the reported techniques and materials was high and
      not statistically different. The incidence of major complications such a
      meningitis, subdural hematoma, and intracranial abscess was less than 1% for each
      complication. CONCLUSION: The endoscopic approach is highly effective and is
      associated with low morbidity. The literature supports the endoscopic approach
      using a variety of techniques and materials for the repair of CSF leaks.

PMID- 10892691
TI  - New guidelines for endoscopic localization of the anterior ethmoidal artery: a
      cadaveric study.
AB  - OBJECTIVES: To determine objective data to improve the methods of identification
      of the anterior ethmoidal artery during endoscopic dissection. STUDY DESIGN:
      Cadaveric dissection of adult human heads. METHODS: A 0 degrees, 4-mm rigid
      endoscope was used to guide uncinectomy and frontoethmoidectomy. The location of
      the anterior ethmoidal artery was first determined visually and then confirmed by
      passing a needle through the anterior ethmoidal foramen from the orbit into the
      nose in all cases. The distances were endoscopically measured using a simple
      ruler between two nasal landmarks and the anterior ethmoidal artery. RESULTS:
      Fifty-six nasal fossae in 28 cadavers were dissected endoscopically. The median
      distance between the artery and the "axilla" formed by the anterior attachment of
      the middle turbinate to the lateral nasal wall was 20 mm (range, 17-25 mm),
      irrespective of the side. The measurement differed by less than 2 mm between the
      sides in the same individual. The median distance between the artery and the
      "axilla" formed by the medial and lateral crura of the lower lateral cartilage
      (superomedial edge of the nostril) was 62 mm (range, 55-75 mm) for both sides.
      The artery was found to be in direct alignment with the two "axillae" formed by
      the middle turbinate and the nostril edge. CONCLUSIONS: The distance between the
      ethmoidal artery and the axilla of the middle turbinate showed the least
      intraindividual and interindividual variations. The tip of the endoscope (or the
      ruler) points directly at the anterior ethmoidal artery in the fovea ethmoidalis
      when its edge is aligned with the two nasal landmarks. These simple guidelines
      can aid the identification of the artery in endoscopic frontoethmoidectomy.

PMID- 10892692
TI  - Frontal sinus stents.
AB  - OBJECTIVES: The formation of scar tissue, synechiae, or osteogenesis in the
      narrow frontal outflow tract after instrumentation of the frontal sinus has led
      to attempts to enlarge the frontal duct or stenting. STUDY DESIGN: Prospective
      pilot study. RESULTS: Sixty-four Freeman frontal sinus stents were used to
      maintain patency in 46 patients. Stents were inserted using an endoscopic
      technique in 26 sinuses containing polyps, 20 with pansinusitis, and 18 cavities
      with stenosis of the frontal duct. External incisions with frontal sinusotomy
      were required to remove the stenosis and insert the stent in nine sinuses.
      Polypoid degeneration, granulation, purulent drainage, and lateralization of the
      middle turbinate were encountered infrequently. Frontal obliteration was
      subsequently required in six sinuses. CONCLUSION: The Freeman frontal sinus stent
      prevented blockage of the outflow tract in patients who had removal of disease in
      the sinus or duct or treatment of frontal stenosis.

PMID- 10892693
TI  - Regulation of immunoglobulin secretion by plasma cells infiltrating nasal polyps.
AB  - OBJECTIVE/HYPOTHESIS: To learn more about the role of plasma cells infiltrating
      nasal polyps in the pathogenesis of nasal polyposis, we examined their function
      by analyzing immunoglobulin (Ig) production and the factors implicated in the
      secretion. STUDY DESIGN: A series of 19 consecutive nasal polyp tissue samples
      and, as a control, peripheral blood samples from the same patients, were studied
      by histopathological and immunological examination. METHODS: Hematoxylin-eosin
      and immunohistochemical staining was carried out to identify plasma cells
      infiltrating nasal polyps. Nasal polyp mononuclear cells (NPMNCs) were purified
      from nasal polyp tissue samples, and Ig-secreting cells were identified in
      cytospin preparations stained with fluorescein isothiocyanate-conjugated
      antibodies against IgA, IgG, IgM, and IgE. Purified NPMNCs were cultured in basal
      conditions and after the addition of several stimuli. Ig secreted into the
      culture supernatants was evaluated by an enzyme-linked immunosorbent assay.
      RESULTS: Plasma cells accounted for an important fraction of the inflammatory
      infiltrate. The main Ig isotype synthesized by these cells was IgA, whereas
      little IgE was detected. In vitro cultures demonstrated that the plasma cells
      actively secreted Ig for a short period. When cytokine dependence was analyzed,
      interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) were shown to
      be partially responsible for the Ig production. Dependence on CD95-mediated
      apoptosis was not observed. CONCLUSIONS: Nasal polyp-infiltrating plasma cells
      are mainly IgA-secreting cells, the latter property being related to the mucosal
      immune system. The IgA production is partly dependent on IL-10 and TNF-alpha. The
      absence of IgE-secreting cells in most of the samples suggests that a type I
      hypersensitivity reaction is not essential for the development of nasal polyp.

PMID- 10892694
TI  - Clinical study and literature review of nasal irrigation.
AB  - OBJECTIVES/HYPOTHESIS: Nasal disease, including chronic rhinosinusitis and
      allergic rhinitis, is a significant source of morbidity. Nasal irrigation has
      been used as an adjunctive treatment of sinonasal disease. However, despite an
      abundance of anecdotal reports, there has been little statistical evidence to
      support its efficacy. The objective of this study was to determine the efficacy
      of the use of pulsatile hypertonic saline nasal irrigation in the treatment of
      sinonasal disease. STUDY DESIGN: A prospective controlled clinical study.
      METHODS: Two hundred eleven patients from the University of California, San Diego
      (San Diego, CA) Nasal Dysfunction Clinic with sinonasal disease (including
      allergic rhinitis, aging rhinitis, atrophic rhinitis, and postnasal drip) and 20
      disease-free control subjects were enrolled. Patients irrigated their nasal
      cavities using hypertonic saline delivered by a Water Pik device using a
      commercially available nasal adapter twice daily for 3 to 6 weeks. Patients rated
      nasal disease-specific symptoms and completed a self-administered quality of well
      being questionnaire before intervention and at follow-up. RESULTS: Patients who
      used nasal irrigation for the treatment of sinonasal disease experienced
      statistically significant improvements in 23 of the 30 nasal symptoms queried.
      Improvement was also measured in the global assessment of health status using the
      Quality of Well-Being scale. CONCLUSIONS: Nasal irrigation is effective in
      improving symptoms and the health status of patients with sinonasal disease.

PMID- 10892695
TI  - Evaluating the role of magnetic resonance imaging scans in the surgical
      management of acoustic neuromas.
AB  - OBJECTIVE: To assess the reliability of magnetic resonance imaging (MRI) in
      predicting the size and position of an acoustic neuroma, with particular
      reference to the intracanalicular portion. STUDY DESIGN: Prospective study
      comparing the position of the tumor in the internal auditory canal on fast spin
      echo MRI with the actual position measured intraoperatively. METHODS: The study
      was performed in a tertiary referral neurotology center, encompassing both the
      public and private health care systems. Fifteen consecutive patients admitted for
      acoustic neuroma removal via the translabyrinthine approach were studied. The
      main outcome measure was tumor position in the internal auditory canal expressed
      in millimeters, accurate to the nearest 0.5 mm. RESULTS: The fast spin-echo MRI
      was accurate within an error of 1 mm in predicting the lateral extent of the
      tumor in the internal auditory canal. CONCLUSION: Fast spin-echo MRI can
      accurately predict the lateral extent of an acoustic neuroma and allow accurate
      planning of the surgical approach.

PMID- 10892696
TI  - Structural changes and protein expression in the mastoid bone adjacent to
      cholesteatoma.
AB  - OBJECTIVE: Cholesteatoma of the mastoid and middle ear causes erosion of nearby
      bone. In this study we examined the mastoid bone adjacent to cholesteatoma and
      compared it with normal mastoid bone. In particular, noncollagenous proteins,
      which have a special structural and functional role in bone, were addressed.
      STUDY DESIGN: Nine mastoid specimens with cholesteatoma and four normal specimens
      obtained at surgery were examined. METHODS: Histological and immunohistochemical
      methods were employed to evaluate the nature of structure and noncollagenous
      protein content changes in the mastoid bone affected by cholesteatoma. RESULTS:
      The bone associated with cholesteatoma had structural changes as a noncontinuous
      periosteum, empty lacunae, irregular cement lines, and, specifically, the
      appearance of eosinophilic vesicles at the interface between the bone and
      cholesteatoma Immunohistochemistry demonstrated that noncollagenous proteins were
      apparently absent in the affected mastoid bone. Bone remote from the
      cholesteatoma seemed normal. CONCLUSIONS: These findings demonstrate for the
      first time the changes in the noncollagenous protein content in the mastoid bone
      affected directly by cholesteatoma These changes could be a result of a direct
      influence of cholesteatoma-derived products on the osteoblast.

PMID- 10892697
TI  - Application of the vestibular disorders activities of daily living scale.
AB  - OBJECTIVE: Existing scales of functional performance are either insufficiently
      sensitive or omit some important daily life tasks. This paper demonstrates that a
      new scale of self-perceived disablement in the vestibularly impaired population
      the Vestibular Disorders Activities of Daily Living Scale (VADL)-differentiates
      between disabled and healthy persons and evaluates the associations of this
      assessment with other measures of vestibular disorders. STUDY DESIGN:
      Prospective. METHODS: Subjects were 1) asymptomatic, healthy adults, 2) patients
      with benign paroxysmal positional vertigo, 3) patients with chronic
      vestibulopathy excluding Meniere's disease, postsurgical vertigo, and
      postconcussion vertigo, and 4) family members. Patient were assessed on the VADL,
      the Dizziness Handicap Inventory, level of vertigo, and computerized dynamic
      posturography. Healthy subjects and family members completed the VADL. RESULTS:
      The VADL differentiates healthy persons from patients but does not differentiate
      between patient groups. Patients perceived themselves as more independent than
      their spouses perceived them to be. Scores are weakly correlated with vertigo
      frequency and posturography scores for conditions with unreliable kinesthesia and
      absent or unreliable vision. The VADL is more responsive to higher levels of
      impairment than the Dizziness Handicap Inventory. CONCLUSIONS: This well-normed,
      self-administered scale of self-perceived disablement is useful for evaluating
      the functional status of patients with peripheral vestibular disorders.
      Perceptions of patients and significant others vary, but scores are moderately
      correlated with some standard measures of vestibular function. As it assesses a
      different domain of function than do standard diagnostic tests, the VADL will
      augment these tests during initial evaluation and may be useful for assessing
      posttreatment change.

PMID- 10892698
TI  - Neck dissection for advanced lymph node metastasis before definitive radiotherapy
      for primary carcinoma of the head and neck.
AB  - OBJECTIVE: To evaluate the outcome of neck dissection for advanced metastasis and
      subsequent planned radiotherapy to the neck and primary tumor. STUDY DESIGN:
      Single-center, retrospective case series. METHODS: From 1988 to 1998, 37
      previously untreated patients were included into the study protocol. Two had a
      single tumor-positive neck node and the remaining 35 had multiple tumor-positive
      neck nodes (mean number, 6.0). Extranodal spread was reported in 35 cases (95%);
      mean nodal size was 5.7 cm (SD, 2.4 cm). Five patients (14%) were not irradiated
      or were irradiated with palliative intention. Of the remaining patients, 30
      received irradiation of 60 Gy or more to the neck and the primary tumor (mean
      dose, 66.9 Gy; SD, 4.2 Gy). Cumulative survival distributions were estimated by
      the Kaplan-Meier method, and differences between groups were analyzed with the
      log-rank test. RESULTS: Treatment-related mortality was observed in three
      patients (8%). Disease-specific survival was 49% at 2 years and the overall
      locoregional control rate was 43% at 2 years. Patients with T1 to T2 primary
      lesions were compared with those with advanced primary disease, and the 2-year
      local control rates were 76% and 47%, respectively (P = .056). The following
      prognostic factors were identified for distant metastasis: three or more positive
      nodes (P = .037), positive surgical margins in the neck dissection specimen (P =
      .004), and time from diagnosis until neck dissection of 23 days or more (P =
      .043). The influence of distant metastasis on disease-specific survival was
      evident (P = .0003). CONCLUSION: Patients with low-T-stage tumors have a better
      local control rate with this regimen and survival depends on the status of the
      neck.

PMID- 10892700
TI  - In vivo interaction of cis-platinum and fosfomycin on squamous cell carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: Cis-platinum is the most frequently used chemotherapeutic
      agent for the treatment of head and neck squamous cell carcinoma (SCCA).
      Ototoxicity and nephrotoxicity continue to be the primary dose-limiting
      toxicities encountered. Fosfomycin, a broad-spectrum antibiotic, has been
      previously shown to be both otoprotective and nephroprotective against cis
      platinum toxicity. Previous in vitro work demonstrated that fosfomycin does not
      inhibit the tumoricidal actions of cis-platinum. This study tests whether
      fosfomycin inhibits cisplatinum in vivo. METHODS: An SCCA cell line was grown in
      vivo in four groups of nude mice, which then received no treatment, standard-dose
      cis-platinum, high-dose cis-platinum, or high-dose cis-platinum with fosfomycin.
      RESULTS: Fosfomycin did not inhibit the tumoricidal activity of cis-platinum.
      Mice treated with fosfomycin also had longer survival, which is probably due to
      lessening of immediate cis-platinum systemic toxicity. CONCLUSION: This study
      shows that fosfomycin in combination with cis-platinum may be useful in treating
      advanced, and possibly relatively chemoresistant, SCCA of the head and neck.

PMID- 10892699
TI  - Transoral CO2 laser for surgical management of glottic carcinoma in situ.
AB  - OBJECTIVES/HYPOTHESIS: In carcinoma in situ (CIS) tumors malignant cells have not
      penetrated the basement membrane and therefore have no metastatic potential.
      Treatment strategies of CIS are topics of ongoing discussion. The aim of this
      study was to evaluate long-term results of CO2 laser therapy in laryngeal CIS.
      METHODS: From 1986 to 1995, 29 patients with glottic CIS with a minimum follow-up
      of 2 years were treated initially with transoral CO2 laser surgery and were
      included is this series. RESULTS: A complete removal of the tumor was possible
      with superficial laser cordectomy in 21 patients and with subligamental laser
      cordectomy in 8 cases. There was no tumor-related death in this series. Repeated
      laser resections were performed in four patients for local recurrences. No
      patient required total laryngectomy or radiotherapy during a follow-up ranging
      from 25 to 143 months. CONCLUSIONS: Local control rates presented in this study
      are superior to those previously reported with conventional surgery and similar
      to those after radiotherapy. The ultimate rate of larynx preservation was seven
      times higher than reported after radiotherapy. Our results add further support to
      the observation that laser surgery is the best treatment option for CIS of the
      larynx. Based on the material of this study, recommended treatment for CIS is CO2
      laser resection in combination with a meticulous follow-up for early recognition
      of local recurrence.

PMID- 10892701
TI  - Genetic analysis in the diagnosis of familial paragangliomas.
AB  - OBJECTIVES: In the management of two related patients with multicentric glomus
      jugulare tumors, given the incidence of 1:30,000 with approximately 20% familial
      cases, our objective was to review the genetic characteristics and inheritance
      patterns of these tumors and to determine what molecular genetic screening
      possibilities exist for the phenotypically normal family members. In addition,
      our aim was to review the incidence of various multicentric paraganglioma (PGL)
      tumor location combinations. METHODS: Molecular genetic linkage analysis testing
      was performed on the 2 patients and 14 other unaffected family members. We report
      the results of this screening and review the literature on the incidence and
      genetics of paragangliomas. RESULTS: The inheritance pattern in the literature
      demonstrates autosomal dominant transmission with maternal imprinting
      (inactivation). The proclivity for multicentric origin increases to 26% in
      familial cases, as reflected in our patients. In addition to the two patients,
      four unaffected family members demonstrated the presence of the disease haplotype
      at chromosome band 11q23, which indicates a very high likelihood of developing a
      paraganglioma, given the highly penetrant nature of the disease. CONCLUSIONS: It
      is clear that the familial PGL gene locus is situated at chromosome 11q23. The
      gene itself and its exact degree of penetrance, however, still await
      identification. Since early detection of paragangliomas reduces the incidence of
      morbidity and mortality, genotypic analysis as a screening tool in families of
      affected patients should play a front-line diagnostic role, leading to more
      timely and cost-effective patient management.

PMID- 10892702
TI  - Simple reconstruction of large pharyngeal defects with free jejunal transfer.

PMID- 10892703
TI  - A technique to prevent cerebrospinal fluid leakage after translabyrinthine
      approach.

PMID- 10892704
TI  - Tonsillectomy using an ultrasonically activated scalpel.

PMID- 10892705
TI  - Cost-utility analysis of pediatric cochlear implantation.

PMID- 10892706
TI  - Recovery from deafness after removal of a large acoustic neurinoma.

PMID- 10892707
TI  - Rationale of a new classification for the group of primary cutaneous lymphomas.
AB  - In the last decade many studies showed that primary cutaneous lymphomas have
      another clinical behavior and prognosis, and therefore require a different
      therapeutic approach, as compared with their primary nodal equivalents. Because,
      until recently, classification systems for non-Hodgkin's lymphomas were purely
      based on histologic criteria, and did not recognize the special character of
      these lymphomas, primary cutaneous lymphomas were not uncommonly diagnosed
      incorrectly and/or treated inappropriately with unnecessarily aggressive
      therapies. For that reason the Cutaneous Lymphoma Group of the European
      Organization for Research and Treatment of Cancer (EORTC) proposed a separate
      classification for the group of primary cutaneous lymphomas. This EORTC
      classification is consistently based on a combination of clinical, histologic,
      immunophenotypical and genetic criteria, and includes well-defined and
      recognizable disease entities. It contains a limited number of cutaneous T-cell
      lymphomas and cutaneous B-cell lymphomas, which together constitute more than 95%
      of all primary cutaneous lymphomas. Herein, the rationale and the basic
      principles of the EORTC classification are presented, and the relationship
      between the EORTC classification and other recent classification systems, such as
      the Revised European-American Classification for Lymphoid Neoplasms (REAL
      classification) and the proposed World Health Organization classification, are
      discussed.

PMID- 10892708
TI  - Pathogenesis of cutaneous lymphomas.
AB  - Cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders
      derived from T cells, B cells and, in rare cases, natural killer cells. The
      precise mechanisms of the lymphomagenesis are still obscure. However, there are
      various factors involved. These factors include environmental, especially
      infectious factors, translocations, mutations and genetic instability. The
      special microenvironment in the skin is responsible for the peculiar behavior of
      these neoplasms by providing various key factors, such as adhesion molecules and
      cytokines. Newly identified molecular disturbances in cutaneous lymphomas might
      be targeted by specific molecular or immunologic interventions in the future.

PMID- 10892709
TI  - Impact of molecular analysis in the diagnosis of cutaneous lymphoid infiltrates.
AB  - The diagnosis and classification of cutaneous lymphomas is a challenge for the
      dermatopathologist. This is particularly true for determining the distinction
      between a malignant lymphoma and a benign reactive infiltrate (pseudolymphoma).
      Recent advances in molecular genetics, as the determination of clonality of
      lymphoid infiltrates, have emerged as an important tool to overcome these
      diagnostic dilemmas. In our experience, more than 90% of cutaneous T-cell
      lymphomas have a rearrangement of the T-cell receptor gamma chain gene, whereas
      clonal rearrangements in cutaneous T-cell pseudolymphomas could not be found.
      However, the demonstration of clonality does not necessarily indicate malignancy.
      There have been several reports that have identified clonal lymphoid
      proliferations in pityriasis lichenoides et varioliformis acuta, pseudolymphomas,
      and lichen planus. For this reason one must carefully evaluate the information
      that is provided by these techniques. The results should always correlate with
      clinical, histologic, and immunophenotypic data to achieve the correct diagnosis.

PMID- 10892710
TI  - Mycosis fungoides: classic disease and variant presentations.
AB  - Mycosis fungoides is a peripheral non-Hodgkin's T-cell neoplastic process,
      representing the most common type of primary cutaneous malignant lymphoma.
      Neoplastic lesions classically show skin predilection and characteristic clinical
      and histologic features in patch, plaque, and tumor stages. In addition, several
      clinicopathologic variants of mycosis fungoides have been delineated, including
      poikiloderma atrophicans vasculare (parapsoriasis variegata), Sezary syndrome,
      granulomatous mycosis fungoides, hypopigmented mycosis fungoides,
      folliculocentric mycosis fungoides, syringotropic mycosis fungoides, and Woringer
      Kolopp disease. We will review the salient features of patch, plaque, and tumor
      stage mycosis fungoides in this article and follow with a discussion of these
      variant clinicopathologic presentations and of therapeutic modalities.

PMID- 10892711
TI  - Sezary syndrome: diagnostic criteria and therapeutic options.
AB  - Sezary syndrome (SS) is a rare form of erythrodermic cutaneous T-cell lymphoma
      with hematological involvement and a poor prognosis. Therapies include
      photopheresis, with or without interferon, chemotherapy, and total skin electron
      beam therapy. The lack of any randomized studies makes it difficult to assess the
      effect of current therapy on survival. In addition, the different response rates
      reported for individual treatments may depend as much on the criteria used to
      define SS as the therapy itself. This article reviews the diagnostic tests that
      are needed to reliably diagnose SS and offers a critical analysis of current
      treatment options.

PMID- 10892712
TI  - Lymphomatoid papulosis and anaplastic large cell lymphomas of the skin.
AB  - It is now generally accepted that primary CD30+ cutaneous lymphomas comprise a
      clinical and morphologic spectrum in which a clear distinction between
      lymphomatoid papulosis (LyP) and lymphoma cannot always be made. Management
      varies from observation in patients who have relatively asymptomatic,
      spontaneously remitting disease (as in LyP) to multiagent chemotherapy regimens
      with or without autologous stem cell transplantation in patients whose disease
      has spread to involve extracutaneous sites other than regional lymph nodes (as in
      disseminated CD30+ lymphoma). Choosing an appropriate management strategy
      requires correlation of the patient's clinical history (including symptoms) with
      physical exam and pathologic findings. The importance of clinicopathologic
      correlation cannot be overemphasized, because lesions with clinically "benign"
      behavior may appear "malignant" by pathology, and failure to interpret pathologic
      findings in accordance with the patient's clinical history and physical exam can
      result in unnecessary, overly aggressive, and potentially harmful treatments.
      This review highlights integration of clinical and pathologic features of these
      primary cutaneous CD30+ lymphoproliferative disorders.

PMID- 10892713
TI  - The clinicopathologic spectrum of cytotoxic lymphomas of the skin.
AB  - Cytotoxic lymphomas of the skin comprise a spectrum of peripheral T cell and
      natural killer cell lymphomas with primary or secondary skin manifestations. They
      comprise a broad, heterogeneous group of lymphoproliferative disorders, and are
      characterized by expression of cytotoxic proteins (TIA-1, granzyme A and B, and
      perforin). These lymphomas often show an aggressive clinical course. In this
      article a detailed description of clinical, histopathologic, immunohistochemical,
      and molecular characteristics of cutaneous cytotoxic lymphomas follows a brief
      introduction on cytotoxic lymphocytes.

PMID- 10892714
TI  - The skin-associated lymphoid tissue-related B-cell lymphomas.
AB  - Primary cutaneous B-cell lymphomas (CBCLs) should be clearly separated from non
      Hodgkin's B-cell lymphomas with secondary cutaneous involvement and from
      cutaneous B-cell pseudolymphomas. The majority of CBCLs are characterized by a
      homogeneous clinical presentation and behavior, with good response to local
      radiotherapy, low tendency to extracutaneous spread, and excellent prognosis.
      According to the European Organization for Research on the Treatment of Cancer
      classification of primary cutaneous lymphomas, CBCLs with an indolent behavior
      are divided into 2 subgroups: follicular center cell lymphoma and
      immunocytoma/marginal zone lymphoma, due to putative histologic similarities with
      their purported nodal counterparts. In addition, a third subgroup with
      intermediate prognosis (large B-cell lymphoma of the leg) is identified.
      Conversely, the identification of distinct subgroups is disputable from a
      strictly histologic, immunophenotypic, and genotypic point of view, and has
      neither correlation with the clinical course nor the prognosis of the disease.
      Moreover, the majority of CBCLs show a uniform immunophenotype (CD5-, CD10-) and
      genotype (lack of bcl-1/bcl-2 and c-myc gene rearrangement) of neoplastic cells.
      Therefore, we favor the use of the term Skin-Associated Lymphoid Tissue (SALT)
      related B-cell lymphomas, due to the close similarities between CBCLs and mucosa
      associated lymphoid tissue (MALT) lymphomas, and the evidence for an acquired B
      cell arm of SALT.

PMID- 10892715
TI  - Primary cutaneous large B-cell lymphomas.
AB  - According to the European Organization for Research and Treatment of Cancer
      classification, primary cutaneous large B-cell lymphomas are subdivided into 2
      groups: follicle center cell large B-cell lymphomas and large B-cell lymphomas of
      the leg. The first type predominantly affects middle-aged adults with an equal
      gender distribution and presents with lesions on the head and trunk. Histology
      shows proliferations of predominantly large cleaved cells. The prognosis is
      excellent, with a 5-year survival rate >90%. The second group predominantly
      affects elderly females. Histologically the lesions are composed of centroblasts
      and/or immunoblasts (large round cells). The prognosis is more unfavorable with a
      5-year survival rate of 50%. Intravascular large B-cell lymphoma is still
      classified as a provisional entity.

PMID- 10892716
TI  - Cutaneous lymphoid hyperplasias.
AB  - Benign hyperplastic lymphoid infiltrates of the skin (pseudolymphoma, older term)
      simulate lymphoma clinically and histologically. They can be divided into B-cell
      predominant (typical cutaneous lymphoid hyperplasia (CLH), angiolymphoid
      hyperplasia, Kimura's disease, and Castleman's disease) and T-cell predominant (T
      cell CLH, lymphomatoid contact dermatitis, and lymphomatoid drug eruption). Both
      types may represent exaggerated reactions to diverse external antigens (insect
      bite, tattoo, zoster, trauma, among others). A composite assessment of clinical
      presentation and behavior, routine histology, immunophenotyping, and molecular
      studies is essential for the diagnosis of benign cutaneous lymphoid infiltrates.
      Treatment includes antibiotics, intralesional and systemic corticosteroids,
      excision, radiotherapy, and immunosuppressants. Treatment depends on the
      assessment and biologic behavior, which is usually benign. Molecular biologic
      analysis has shown that a significant proportion of cases harbor occult B- or T
      cell clones (clonal CLH). Progression to overt cutaneous lymphoma has been
      observed in a minority of cases. Patients with clonal populations of B or T cells
      and persistent lesions should be closely observed for emergence of a lymphoma.

PMID- 10892717
TI  - Treatment of cutaneous T-cell lymphomas.
AB  - Primary cutaneous T-cell lymphomas (CTCL), representing a heterogeneous group of
      non-Hodgkin's lymphomas (NHL), can be defined as clonal proliferation of skin
      infiltrating T lymphocytes primarily presenting in the cutaneous compartment.
      They show a considerable variation in clinical presentation, histology,
      immunophenotype, and prognosis, which is best reflected by the proposal of the
      Cutaneous Lymphoma Study Group of the European Organization for Research and
      Treatment of Cancer (EORTC). Due to the heterogeneity of CTCL and the lack of
      curative therapy regimens, multiple strategies have been proposed for the
      management of the different CTCL entities. This includes topical application of
      corticosteroids, nitrogen mustard or carmustine (BCNU), radiotherapy, including
      total skin electron beam irradiation, photo(chemo)therapy, biological response
      modifiers, cytostatic chemotherapy, and combined regimens. More recently, fusion
      proteins and peptide vaccines have been introduced in the management of CTCL.
      Classification, staging, and treatment modalities are discussed in detail and
      summarized in a stage-adapted therapy regimen for CTCL.

PMID- 10892718
TI  - New developments in extracutaneous lymphomas.
AB  - The recently proposed World Health Organization classification of neoplastic
      diseases of the lymphoid tissues is based on the principles of the Revised
      European-American Classification of Lymphoid Neoplasms introduced in 1994. Use of
      these classifications implies a new approach to lymphoma diagnosis, especially
      because of the inclusion of clinical data among which the site of involvement
      (nodal v extranodal) is very important. Recent technical advances allowing
      molecular biological investigations on the single cell level helped gain new
      insights into the cellular origin of B-cell lymphomas. Tumor cells of the
      majority of B-cell non-Hodgkin's lymphomas (NHL) harbor somatically mutated
      immunoglobulin variable region genes, and are therefore derived from germinal
      center B cells or their descendants. The same is true for Hodgkin's disease,
      which (at least in the majority of cases) is a germinal center derived B-cell
      lymphoma. Significant news on the molecular pathogenesis of NHL include the
      prognostically relevant dichotomy of B-CLL, the involvement of translocations
      affecting 3q27 in 20% to 40% of diffuse large B-cell lymphomas (DLBCL), the
      prognostical implication of the t(2;5) in anaplastic large cell lymphoma, and
      detection of the t(11;18) in gastric mucosa-associated lymphoid tissue (MALT)
      type lymphoma. A major step forward with regard to gastric MALT-type lymphoma
      therapy was the discovery of a causal relationship between Helicobacter pylori
      infection and lymphomagenesis. Cyclophosphamide, doxorubicin, vincristine, and
      prednisone (CHOP) chemotherapy remains the golden standard for DLBCL treatment.

PMID- 10892719
TI  - Controversies in cutaneous lymphomas.
AB  - Recently great advances were achieved in the recognition and classification of
      primary cutaneous lymphomas. With this increased knowledge, one must realize that
      we must deal with new concepts that are sometimes confusing and controversial.
      The following controversial subjects are presented in this article: (1)
      Classification of cutaneous lymphomas; (2) Cutaneous T-cell lymphoma with
      small/medium-sized pleomorphic cells as a distinct entity; (3) Primary cutaneous
      follicle center lymphoma and marginal zone lymphoma/ immunocytoma.

PMID- 10892720
TI  - Proteomics: applications and opportunities in preclinical drug development.
AB  - Advances in DNA sequencing and the near-term availability of whole genome
      sequences for several pharmaceutically relevant organisms promise to dramatically
      alter the breadth and scale of high-throughput proteomic studies. The substantial
      amount of literature is available in the public domain, demonstrate the potential
      of proteomics in the preclinical phases of pharmaceutical development. Over the
      next few years, it is anticipated that functional genomics and proteomics will
      have major impacts on the clinical phases of drug development. Expected benefits
      are earlier proof-of-concept studies in man and increased efficiency of clinical
      trials through the availability of biologically relevant markers for drug
      efficacy and safety.

PMID- 10892721
TI  - Mass spectrometry: a tool for the identification of proteins separated by gels.
AB  - Mass spectrometry (MS) has become the technique of choice to identify proteins.
      This has been largely accomplished by the combination of high-resolution two
      dimensional (2-D) gel separation with robotic sample preparation, automated MS
      measurement, data analysis, and database query. Developments during the last five
      years in MS associated with protein gel separation are reviewed.

PMID- 10892722
TI  - Bladder squamous cell carcinoma biomarkers derived from proteomics.
AB  - Proteomics provide powerful technology for analyzing the expression levels of
      thousands of proteins simultaneously both in health and disease. Here, we review
      proteomic strategies that we have developed to identify metaplastic lesions in
      bladder squamous cell carcinomas as well as biomarkers in the urine for follow-up
      studies of squamous cell carcinoma (SCC)-bearing patients.

PMID- 10892723
TI  - Two-dimensional electrophoresis of liver proteins: characterization of a drug
      induced hepatomegaly in rats.
AB  - Two-dimensional electrophoresis (2-DE) of liver proteins was applied to further
      characterize an unusual drug-induced increase in hepatocellular rough endoplasmic
      reticulum (RER) in Sprague-Dawley rats given a substituted pyrimidine derivative.
      Absolute liver weights of drug-treated rats (9.9 +/- 0.4 g) increased above
      vehicle-treated controls (7.2 +/- 0.2 g) by 37%. Light microscopy revealed
      diffuse granular basophilia of the hepatocellular cytoplasm, uncharacteristic of
      hepatocytes and suggested cells rich in ribosomes, which was confirmed by
      electron microscopy. Immunostaining for cell proliferation, viz., 5-bromo-2'
      deoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA), indicated
      marked hepatocellular proliferative activity. 2-DE of solubilized liver using an
      ISO-DALT gel system indicated significant (p<0.001) quantitative changes in at
      least 17 liver proteins (12 increased, 5 decreased) compared to controls. The
      protein with the largest increase was homologous to acute-phase reactant,
      contrapsin-like protein inhibitor-6. Other markedly upregulated proteins were
      methionine adenosyltransferase, a catalyst in methionine/ATP metabolism and
      mitochondrial HMG-CoA synthase, involved in cholesterol synthesis. The
      complementary strategies of 2-DE coupled either with database spot mapping or
      protein isolation and amino acid sequencing successfully identified a subset of
      proteins from xenobiotic-damaged rodent livers, the expression of which differed
      from controls. However, the current bioinformatics platform for rodent hepatic
      proteins and limited knowledge of specific protein functionality restricted
      application of this proteomics profile to further define a mechanistic basis for
      this unusual hepatotoxicity.

PMID- 10892724
TI  - Proteomics to display lovastatin-induced protein and pathway regulation in rat
      liver.
AB  - Lovastatin is a lipid lowering agent that acts by inhibiting 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase, a key regulatory enzyme in
      cholesterol biosynthesis. In this study the pattern of gene network regulation
      induced in hepatic proteins as a response to lovastatin treatment was analyzed by
      proteomics. In livers of male F344 rats treated with 1.6 mg/kg/day lovastatin or
      150 mg/kg/day lovastatin for seven days, 36 proteins were found to be
      significantly altered (p<0.001) in relation to treatment. The changed proteins
      were classified according to their cellular function and participation in
      biochemical pathways. The following observations were made: (i) inhibition of HMG
      CoA reductase provoked a regulatory response in the cholesterol synthesis pathway
      including the induction of cytosolic HMG-CoA synthase and of isopentenyl
      diphosphate delta-isomerase, (ii) manipulation of the lipid metabolism triggered
      alterations in key enzymes of the carbohydrate metabolism, and (iii) lovastatin
      treatment was associated with signs of toxicity as reflected by changes in a
      heterogeneous set of cellular stress proteins involved in functions such as
      cytoskeletal structure, calcium homeostasis, protease inhibition, cell signaling
      or apoptosis. These results present new insights into liver gene network
      regulations induced by lovastatin and illustrate a yet unexplored application of
      proteomics to discover new targets by analysis of existing drugs and the pathways
      that they regulate.

PMID- 10892726
TI  - Two-dimensional database of mouse liver proteins: changes in hepatic protein
      levels following treatment with acetaminophen or its nontoxic regioisomer 3
      acetamidophenol.
AB  - Overdose of acetaminophen (APAP) causes acute hepatotoxicity in rodents and man.
      The mechanism underlying APAP-induced liver injury remains unclear, but
      experimental evidence strongly suggests that activation of APAP and subsequent
      formation of protein adducts are involved in hepatotoxicity. Using proteomics
      technologies, we constructed a two-dimensional protein database for mouse liver,
      comprising 256 different gene products and investigated the proteins affected
      after APAP-induced hepatotoxicity. Adult male mice received a single dose of APAP
      (100 or 300 mg/kg) or its nontoxic regioisomer 3-acetamidophenol (AMAP, 300
      mg/kg). The extent of liver damage was assessed 8 h after administration by
      increased liver enzyme release and histopathology. Changes in the protein level
      were studied by comparison of the intensities of the corresponding spots on two
      dimensional (2-D) gels. The expression level of about 35 of the identified
      proteins was modified due to treatment with APAP or AMAP. The observed changes
      were usually in the order of 10-50% of the control value and were more marked in
      the high- than in the low-dose of APAP-treated animals. Most of the changes
      caused by AMAP occurred in a subset of the proteins modified by APAP. Many of the
      proteins showing changed expression levels are either known targets for covalent
      modification by N-acetyl-p-benzoquinoneimine (NAPQI) or involved in the
      regulation of mechanisms that are believed to drive APAP-induced hepatotoxicity.

PMID- 10892725
TI  - Toxicity of chemical mixtures: proteomic analysis of persisting liver and kidney
      protein alterations induced by repeated exposure of rats to JP-8 jet fuel vapor.
AB  - Male Sprague-Dawley rats were exposed by whole body inhalation to 1000 mg/m3 +/-
      10% JP-8 jet fuel vapor or room air control conditions for 6 h/day, 5 days/week
      for six consecutive weeks. Following a rest period of 82 days rats were
      sacrificed, and liver and kidney tissues examined by proteomic methods for both
      total protein abundance and protein charge modification. Kidney and lung samples
      were solubilized and separated via large scale, high resolution two-dimensional
      electrophoresis (2-DE) and gel patterns scanned, digitized and processed for
      statistical analysis. Through the use of peptide mass fingerprinting, confirmed
      by sequence tag analysis, three altered proteins were identified and quantified.
      Numerical, but not significantly different increases were found in total
      abundance of lamin A (NCBI Accession No. 1346413) in the liver, and of 10
      formyltetrahydrofolate dehydrogenase (10-FTHF DH, #1346044) and glutathione-S
      transferase (GST; #2393724) in the kidneys of vapor-exposed subjects. Protein
      charge modification index (CMI) analysis indicated significant alterations (P <
      0.001) in expressed lamin A and 10-FTHF DH. These persisting changes in liver and
      kidney proteins are discussed in terms of possible alterations in the functional
      capacity of exposed subjects.

PMID- 10892727
TI  - Mouse liver selenium-binding protein decreased in abundance by peroxisome
      proliferators.
AB  - Several studies with two-dimensional gel electrophoresis (2-DE) have shown that
      the abundance of numerous mouse liver proteins is altered in response to
      treatment with chemicals known to cause peroxisome proliferation. The peptide
      masses from tryptic digests of two liver proteins showing dramatic decreases in
      abundance in response to numerous peroxisome proliferators were used to search
      sequence databases. The selenium-binding protein 2 (SBP2 formerly 56 kDa
      acetaminophen-binding protein, AP 56) and selenium-binding protein 1 (SBP1
      formerly 56 kDa selenium-binding protein, SP 56) in mouse liver, proteins with a
      high degree of sequence similarity, were the highest ranked identities obtained.
      Identity with SBP2 was subsequently confirmed by immunodetection with specific
      antiserum. Treatment of mice with 0.025% ciprofibrate resulted in the more basic
      of this pair of proteins being decreased to 30% of control abundance while the
      acidic protein was decreased to 7% of the control amount. Dexamethasone
      treatment, in contrast, caused increases of 80% and 20% in the abundance of the
      acidic and basic forms, respectively. Administration of dexamethasone to mice in
      combination with ciprofibrate produced expression of the acidic SBP2 at 23% of
      the control level and the basic SBP2 at 36%, a slightly moderated reduction
      compared with the decrease that occurred with ciprofibrate alone. These data
      suggest that peroxisome proliferators such as ciprofibrate cause a decrease in
      the abundance of the SBP2, which leads to increased cell proliferation, even in
      the presence of an inhibitor such as dexamethasone. Such a decrease in SBP,
      thought to serve as cell growth regulation factors, could be central to the
      nongenotoxic carcinogenicity of the peroxisome proliferators observed in rodents.

PMID- 10892728
TI  - Proteins of rat serum V: adjuvant arthritis and its modulation by nonsteroidal
      anti-inflammatory drugs.
AB  - The effect of adjuvant arthritis (AA) on the pattern of rat serum proteins
      includes the upregulation of haptoglobin, orosomucoid, alpha2-macroglobulin,
      serine protease inhibitor-3, thiostatin, alpha1-antitrypsin, C-reactive protein,
      and the downregulation of kallikrein-binding protein, alpha1-inhibitor III,
      apolipoprotein A-I, alpha2-HS-glycoprotein, albumin, apolipoprotein A-IV,
      transthyretin and transferrin. Minor changes (+/- 20%) are observed for Gc
      globulin, ceruloplasmin, and alpha1-macroglobulin. AA thus grossly resembles the
      acute inflammatory response elicited by the injection of turpentine, although the
      changes in the levels of negative acute-phase proteins (APP) are smaller in acute
      inflammation. Indomethacine and ibuprofen inhibit the effects of arthritis on the
      synthesis of rat serum proteins in different ways: The former is, on average,
      three times as effective as the latter. Each drug interferes differently with
      different proteins. In animals without AA, both nonsteroidal anti-inflammatory
      drugs (NSAID) mimic the inflammatory pattern to a certain extent, with more
      effect on the negative than on the positive APPs. Overall, the shifts in serum
      protein levels parallel changes in inflammatory parameters such as joint swelling
      and serum interleukin-6 (IL-6) activity. Protein quantitation after two
      dimensional electrophoresis (2-DE) reveals some effects of the drugs per se which
      escape detection by other routine tests.

PMID- 10892729
TI  - A comprehensive characterization of the T-cell antigen receptor complex
      composition by microcapillary liquid chromatography-tandem mass spectrometry.
AB  - It has become apparent that many intracellular signaling processes involve the
      dynamic reorganization of cellular proteins into complex signaling assemblies
      that have a specific subunit composition, function, and subcellular location.
      Since the elements of such assemblies interact physically, multiprotein signaling
      complexes can be isolated and analyzed. Recent technical advances in highly
      sensitive protein identification by electrospray-tandem mass spectrometry have
      dramatically increased the sensitivity with which such analyses can be performed.
      The T-cell antigen receptor (TCR) is an oligomeric transmembrane protein complex
      that is essential to T-cell recognition and function. The extracellular protein
      domains are responsible for ligand binding while intracellular domains generate
      and transduce signals in response to specific receptor-ligand interactions. We
      used microbore capillary chromatography-tandem mass spectrometry to investigate
      the composition of the TCR protein complex isolated from resting and activated
      cells of the murine T-cell line CD11.3. We identified all the previously known
      subunits of the TCR/CD3 complex as well as proteins previously not known to
      associate with the TCR. The catalytic activities of some of these proteins could
      potentially be used to interfere pharmacologically with TCR signaling.

PMID- 10892730
TI  - A general method for the rapid characterization of tyrosine-phosphorylated
      proteins by mini two-dimensional gel electrophoresis.
AB  - Our preliminary results are reported in the investigation of the tyrosine
      phosphorylation cascade triggered by the stimulation of the insulin receptor in
      the adipocyte cell line 3T3-L1 using a mini two-dimensional gel electrophoresis
      approach. The minigel format, 8 x 10 cm, was found sufficiently resolving and
      reproducible to study complex biological samples while considerably increasing
      throughput and lowering costs compared to larger gel formats. Consequently, we
      used the minigel format to rapidly screen a large number of samples, of which
      only the most relevant were then analyzed by optimized, preparative two
      dimensional gels. The accurate localization and relative quantification of
      tyrosine-phosphorylated proteins was performed using a nonradioactive triple
      labeling method. After transfer onto polyvinylidene difluoride (PVDF) membranes,
      proteins were stained with Sypro Ruby to verify the separation quality and to
      localize the general region of interest for immunostaining. The membranes were
      subsequently blocked with polyvinylpyrrolidone-40 and probed with the relevant
      antibodies for visualization of the phosphorylated proteins by chemiluminescence.
      Finally, membranes were stained with colloidal gold to obtain a pattern
      reminiscent of the silver staining of a polyacrylamide gel. We believe that the
      presented strategy can be generalized for any gel application in which a protein
      has to be detected and identified based on its immunoreactivity.

PMID- 10892731
TI  - Deamidation as a widespread phenomenon in two-dimensional polyacrylamide gel
      electrophoresis of human blood plasma proteins.
AB  - The human plasma protein patterns obtained by two-dimensional polyacrylamide gel
      electrophoresis (2-D PAGE) is a good model system for post-translational
      modifications because of the existence of several "ladders" of protein spots
      [Anderson, N. L., Anderson, N. G., Electrophoresis 1991, 12, 883-906], so-called
      "trains" of spots. Our investigation of several proteins, amongst others beta2
      microglobulin and the haptoglobin chains, found the differences in isoelectric
      points (p/) to be due to deamidation of asparagines. After enzymatic cleavage
      with endopeptidases in the 2-D polyacrylamide gel, the asparagine and deamidated
      asparagine containing peptides were separated and quantified by reversed-phase
      HPLC. In order to separate these peptides, a neutral pH system was established
      and, as a result, the differences in hydrophobicity of asparagine-containing and
      deamidated asparagine-containing peptides increased. But how do deamidated
      asparagines contribute to the observed spot pattern? One spot in the 2-D gel
      consists of a mixture of protein species with the same number of deamidated
      asparagines but on different sequence position sites. The difference between the
      spots in the "ladder" is a growing number of negative charges introduced in the
      protein by an increasing number of deamidated asparagines. As a consequence, the
      mass difference between two spots is exactly 1 Da, which is shown in this paper
      for intact protein masses and the corresponding deamidated peptides.

PMID- 10892732
TI  - Tracking pathology with proteomics: identification of in vivo degradation
      products of alphaB-crystallin.
AB  - Soemmerring's ring is one form of "after cataract" that can occur following
      cataract surgery. The ring structure is formed by adherence of the anterior lens
      capsule to the posterior lens capsule. Epithelial cells remaining after surgery
      differentiate into lens fiber cells but the resulting tissue mass does not remain
      transparent. The protein in normal lens and in Soemmerring's rings from four
      individuals was analyzed using two-dimensional (2-D) gel electrophoresis, matrix
      assisted laser desorption/ionization-time of-flight-mass spectrometry (MALDI-TOF
      MS) and image analysis with Phoretix software. The 2-D protein patterns of the
      Soemmerring's rings were generally similar to that of cortical fiber cells of
      normal human lens with some notable exceptions. Several post-translationally
      modified forms of alphaB-crystallin(1-175) were identified. Two degradation
      products, alphaB-crystallin(1-170) and alphaB-crystallin(1-174), each make up 9.5
      27% of the total alphaB-crystallin in the Soemmerring's rings and less than 1% in
      the normal lenses. Other modified forms of alphaB-crystallin are aberrant in the
      fiber cells of the Soemmerring rings relative to normal lens.

PMID- 10892733
TI  - Proteomic analysis of the atrophying rat soleus muscle following denervation.
AB  - A proteomic analysis was performed comparing normal rat soleus muscle to
      denervated soleus muscle at 0.5, 1, 2, 4, 6, 8 and 10 days post denervation.
      Muscle mass measurements demonstrated that the times of major mass changes
      occurred between 2 and 4 days post denervation. Proteomic analysis of the
      denervated soleus muscle during the atrophy process demonstrated statistically
      significant (at the p < 0.01 level) changes in 73 soleus proteins, including
      coordinated changes in select groups of proteins. Sequence analysis of ten
      differentially regulated proteins identified metabolic proteins, chaperone and
      contractile apparatus proteins. Together these data indicate that coordinated
      temporally regulated changes in the proteome occur during denervation-induced
      soleus muscle atrophy, including changes in muscle metabolism and contractile
      apparatus proteins.

PMID- 10892734
TI  - Proteomic analysis of laser capture microdissected human prostate cancer and in
      vitro prostate cell lines.
AB  - Specific populations of normal and malignant epithelium from three radical
      prostatectomy tissue specimens were procured by laser capture microdissection
      (LCM) and analyzed by two-dimensional polyacrylamide gel electrophoresis (2-D
      PAGE). Six proteins that were only seen in malignant cells and two proteins that
      were only seen in benign epithelium were reproducibly observed in two of two
      cases examined. Furthermore, these proteins were not observed in the 2-D PAGE
      profiles from the patient-matched microdissected stromal cell populations, but
      were seen in the protein profiles from the undissected whole cryostat sections.
      One of these proteins was determined to be prostate-specific antigen (PSA) by
      Western blot analysis, and intriguingly the remaining protein candidates were
      found to be at least as abundant as the PSA protein. Comparison of 2-D PAGE
      profiles of microdissected cell with matched in vitro cell lines from the same
      patient, and metastatic prostate cancer cell lines (LnCaP and PC3) showed
      striking differences between prostate cells in vivo and in vitro with less than
      20% shared proteins. The data demonstrate that 2-D PAGE analysis of LCM-derived
      cells can reliably detect alterations in protein expression associated with
      prostate cancer, and that these differentially expressed proteins are produced in
      high enough levels which could allow for their clinical utility as new targets
      for therapeutic intervention, serum markers, and/or imaging markers.

PMID- 10892735
TI  - Automatic poisson peak harvesting for high throughput protein identification.
AB  - High throughput identification of proteins by peptide mass fingerprinting
      requires an efficient means of picking peaks from mass spectra. Here, we report
      the development of a peak harvester to automatically pick monoisotopic peaks from
      spectra generated on matrix-assisted laser desorption/ionisation time of flight
      (MALDI-TOF) mass spectrometers. The peak harvester uses advanced mathematical
      morphology and watershed algorithms to first process spectra to stick
      representations. Subsequently, Poisson modelling is applied to determine which
      peak in an isotopically resolved group represents the monoisotopic mass of a
      peptide. We illustrate the features of the peak harvester with mass spectra of
      standard peptides, digests of gel-separated bovine serum albumin, and with
      Escherictia coli proteins prepared by two-dimensional polyacrylamide gel
      electrophoresis. In all cases, the peak harvester proved effective in its ability
      to pick similar monoisotopic peaks as an experienced human operator, and also
      proved effective in the identification of monoisotopic masses in cases where
      isotopic distributions of peptides were overlapping. The peak harvester can be
      operated in an interactive mode, or can be completely automated and linked
      through to peptide mass fingerprinting protein identification tools to achieve
      high throughput automated protein identification.

PMID- 10892736
TI  - Tandem mass spectrometry methods for definitive protein identification in
      proteomics research.
AB  - Optimized procedures have been developed for the addition of sulfonic acid groups
      to the N-termini of low-level peptides. These procedures have been applied to
      peptides produced by tryptic digestion of proteins that have been separated by
      two-dimensional (2-D) gel electrophoresis. The derivatized peptides were
      sequenced using matrix-assisted laser desorption/ionization (MALDI) post-source
      decay (PSD) and electrospray ionization-tandem mass spectrometry methods.
      Reliable PSD sequencing results have been obtained starting with sub-picomole
      quantities of protein. We estimate that the current PSD sequencing limit is about
      300 fmol of protein in the gel. The PSD mass spectra of the derivatized peptides
      usually allow much more specific protein sequence database searches than those
      obtained without derivatization. We also report initial automated electrospray
      ionization-tandem mass spectrometry sequencing of these novel peptide
      derivatives. Both types of tandem mass spectra provide predictable fragmentation
      patterns for arginine-terminated peptides. The spectra are easily interpreted de
      novo, and they facilitate error-tolerant identification of proteins whose
      sequences have been entered into databases.

PMID- 10892737
TI  - Identification of two-dimensionally separated human cerebrospinal fluid proteins
      by N-terminal sequencing, matrix-assisted laser desorption/ionization--mass
      spectrometry, nanoliquid chromatography-electrospray ionization-time of flight
      mass spectrometry, and tandem mass spectrometry.
AB  - Optimal application of biological mass spectrometry (MS) in combination with two
      dimensional polyacrylamide gel electrophoresis (2-D PAGE) of human cerebrospinal
      fluid (CSF) can lead to the identification of new potential biological markers of
      neurological disorders. To this end, we analyzed a number of 2-D PAGE protein
      spots in a human CSF pool using spot co-localization, N-terminal sequencing,
      matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and
      nanoliquid chromatography-electrospray ionization-time of flight-mass
      spectrometry (nanoLC-ESI-TOF-MS) with tandem MS switching. Our constructed CSF
      master contained 469 spots after image analysis and processing of 2-D gels. Upon
      visual inspection of our CSF master with the CSF pattern available on the ExPASy
      server, it was possible to locate and annotate 15 proteins. N-terminal sequence
      analysis and MALDI-MS peptide mass fingerprint analysis of both silver- and
      Coomassie Brilliant Blue (CBB) G-250-stained protein spots after in situ trypsin
      digest not only confirmed nine of the visually annotated spots but additionally
      resolved the identity of another 13 spots. Six of these proteins were not
      annotated on the 2-D ExPASy map: complement C3 alpha-chain (1321-1663),
      complement factor B, cystatin C, calgranulin A, hemoglobin beta-chain, and beta-2
      microglobulin. It was clear that MALDI-MS identification from CBB G-250-stained,
      rather than from silver-stained, spots was more successful. In cases where no N
      terminal sequence and/or no clear MALDI-MS result was available, nanoLC-ESI-TOF
      MS and tandem MS automated switching was used to clarify and/or identify these
      protein spots by generating amino acid sequence tags. In addition, enrichment of
      the concentration of low-abundant proteins on 2-D PAGE was obtained by removal of
      albumin and immunoglobulins from the CSF pool using affinity chromatography.
      Subsequent analysis by 2-D PAGE of the fractionated CSF pool showed various new
      silver-stainable protein spots, of which four were identified by nanoLC-ESI-TOF
      MS and tandem MS switching. No significant homology was found in either protein
      or DNA databases, indicating than these spots were unknown proteins.

PMID- 10892738
TI  - Putting on the brakes: a negative regulatory function for Ena/VASP proteins in
      cell migration.

PMID- 10892739
TI  - Calcineurin signaling and muscle remodeling.

PMID- 10892740
TI  - Sorting and signaling at the Golgi complex.

PMID- 10892741
TI  - Cell biology of virus entry.

PMID- 10892742
TI  - Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of
      the roundabout receptor.
AB  - Drosophila Roundabout (Robo) is the founding member of a conserved family of
      repulsive axon guidance receptors that respond to secreted Slit proteins. Little
      is known about the signaling mechanisms which function downstream of Robo to
      mediate repulsion. Here, we present genetic and biochemical evidence that the
      Abelson (Abl) tyrosine kinase and its substrate Enabled (Ena) play direct and
      opposing roles in Robo signal transduction. Genetic interactions support a model
      in which Abl functions to antagonize Robo signaling, while Ena is required in
      part for Robo's repulsive output. Both Abl and Ena can directly bind to Robo's
      cytoplasmic domain. A mutant form of Robo that interferes with Ena binding is
      partially impaired in Robo function, while a mutation in a conserved cytoplasmic
      tyrosine that can be phosphorylated by Abl generates a hyperactive Robo receptor.

PMID- 10892743
TI  - Negative regulation of fibroblast motility by Ena/VASP proteins.
AB  - Ena/VASP proteins have been implicated in cell motility through regulation of the
      actin cytoskeleton and are found at focal adhesions and the leading edge. Using
      overexpression, loss-of-function, and inhibitory approaches, we find that
      Ena/VASP proteins negatively regulate fibroblast motility. A dose-dependent
      decrease in movement is observed when Ena/VASP proteins are overexpressed in
      fibroblasts. Neutralization or deletion of all Ena/VASP proteins results in
      increased cell movement. Selective depletion of Ena/VASP proteins from focal
      adhesions, but not the leading edge, has no effect on motility. Constitutive
      membrane targeting of Ena/VASP proteins inhibits motility. These results are in
      marked contrast to current models for Ena/VASP function derived mainly from their
      role in the actin-driven movement of Listeria monocytogenes.

PMID- 10892744
TI  - FOG-2, a cofactor for GATA transcription factors, is essential for heart
      morphogenesis and development of coronary vessels from epicardium.
AB  - We disrupted the FOG-2 gene in mice to define its requirement in vivo. FOG-2(-/-)
      embryos die at midgestation with a cardiac defect characterized by a thin
      ventricular myocardium, common atrioventricular canal, and the tetralogy of
      Fallot malformation. Remarkably, coronary vasculature is absent in FOG-2(-/-)
      hearts. Despite formation of an intact epicardial layer and expression of
      epicardium-specific genes, markers of cardiac vessel development (ICAM-2 and FLK
      1) are not detected, indicative of failure to activate their expression and/or to
      initiate the epithelial to mesenchymal transformation of epicardial cells.
      Transgenic reexpression of FOG-2 in cardiomyocytes rescues the FOG-2(-/-)
      vascular phenotype, demonstrating that FOG-2 function in myocardium is required
      and sufficient for coronary vessel development. Our findings provide the
      molecular inroad into the induction of coronary vasculature by myocardium in the
      developing heart.

PMID- 10892745
TI  - The RNA binding protein Pub1 modulates the stability of transcripts containing
      upstream open reading frames.
AB  - The nonsense-mediated mRNA decay (NMD) pathway functions to degrade transcripts
      containing nonsense codons. Transcripts containing mutations that insert an
      upstream open reading frame (uORF) in the 5'-UTR are degraded through NMD.
      However, several naturally occurring uORF-containing transcripts are resistant to
      NMD. Here we demonstrate that the GCN4 and YAP1 mRNAs, which contain uORFs,
      harbor a stabilizer element (STE) that prevents rapid NMD by interacting with the
      RNA binding protein Pub1. Conversely, a uORF-containing mRNA that lacks an STE,
      such as CPA1, is degraded by the NMD pathway. These results indicate that uORFs
      can play a pivotal role regulating both translation and turnover and that the
      Pub1p is a critical factor that modulates the stability of uORF-containing
      transcripts.

PMID- 10892746
TI  - SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2
      ability to ubiquitinate p53.
AB  - Mdm2 is an E3 ubiquitin ligase for the p53 tumor suppressor protein. We
      demonstrate that Mdm2 is conjugated with SUMO-1 (sumoylated) at Lys-446, which is
      located within the RING finger domain and plays a critical role in Mdm2 self
      ubiquitination. Whereas mutant Mdm2(K446R) is stabilized, it elicits increased
      degradation of p53 and concomitant inhibition of p53-mediated apoptosis. In vitro
      sumoylation of Mdm2 abrogates its self-ubiquitination and increases its ubiquitin
      ligase activity toward p53. Radiation caused a dose- and time-dependent decrease
      in the degree of Mdm2 SUMO-1 modification, which is inversely correlated with the
      levels of p53. Our results suggest that the maintenance of the intrinsic activity
      of a RING finger E3 ubiquitin ligase is sumoylation dependent and that reduced
      Mdm2 sumoylation in response to DNA damage contributes to p53 stability.

PMID- 10892747
TI  - Transient sister chromatid separation and elastic deformation of chromosomes
      during mitosis in budding yeast.
AB  - The accurate segregation of chromosomes at mitosis requires that all pairs of
      chromatids bind correctly to microtubules prior to the dissolution of sister
      cohesion and the initiation of anaphase. By analyzing the motion of GFP-tagged S.
      cerevisiae chromosomes, we show that kinetochore-microtubule attachments impose
      sufficient tension on sisters during prometaphase to transiently separate
      centromeric chromatin toward opposite sides of the spindle. Transient separations
      of 2-10 min duration occur in the absence of cohesin proteolysis, are
      characterized by independent motion of the sisters along the spindle, and are
      followed by the apparent reestablishment of sister linkages. The existence of
      transient sister separation in yeast explains the unusual bilobed localization of
      kinetochore proteins and supports an alternative model for spindle structure. By
      analogy with animal cells, we propose that yeast centromeric chromatin acts as a
      tensiometer.

PMID- 10892748
TI  - A novel mechanism of TRAF signaling revealed by structural and functional
      analyses of the TRADD-TRAF2 interaction.
AB  - TRAF proteins are major mediators for the cell activation, cell survival, and
      antiapoptotic functions of the TNF receptor superfamily. They can be recruited to
      activated TNF receptors either by direct interactions with the receptors or
      indirectly via the adaptor protein TRADD. We now report the structure of the
      TRADD-TRAF2 complex, which is highly distinct from receptor-TRAF2 interactions.
      This interaction is significantly stronger and we show by an in vivo signaling
      assay that TRAF2 signaling is more readily initiated by TRADD than by direct
      receptor-TRAF2 interactions. TRADD is specific for TRAF1 and TRAF2, which ensures
      the recruitment of clAPs for the direct inhibition of caspase activation in the
      signaling complex. The stronger affinity and unique specificity of the TRADD
      TRAF2 interaction are crucial for the suppression of apoptosis and provide a
      mechanistic basis for the perturbation of TRAF recruitment in sensitizing cell
      death induction.

PMID- 10892749
TI  - Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA
      double-strand break repair and the ABC-ATPase superfamily.
AB  - To clarify the key role of Rad50 in DNA double-strand break repair (DSBR), we
      biochemically and structurally characterized ATP-bound and ATP-free Rad50
      catalytic domain (Rad50cd) from Pyrococcus furiosus. Rad50cd displays ATPase
      activity plus ATP-controlled dimerization and DNA binding activities. Rad50cd
      crystal structures identify probable protein and DNA interfaces and reveal an ABC
      ATPase fold, linking Rad50 molecular mechanisms to ABC transporters, including P
      glycoprotein and cystic fibrosis transmembrane conductance regulator. Binding of
      ATP gamma-phosphates to conserved signature motifs in two opposing Rad50cd
      molecules promotes dimerization that likely couples ATP hydrolysis to dimer
      dissociation and DNA release. These results, validated by mutations, suggest
      unified molecular mechanisms for ATP-driven cooperativity and allosteric control
      of ABC-ATPases in DSBR, membrane transport, and chromosome condensation by SMC
      proteins.

PMID- 10892750
TI  - Crystal structure of the lambda repressor C-terminal domain provides a model for
      cooperative operator binding.
AB  - Interactions between transcription factors bound to separate operator sites
      commonly play an important role in gene regulation by mediating cooperative
      binding to the DNA. However, few detailed structural models for understanding the
      molecular basis of such cooperativity are available. The c1 repressor of
      bacteriophage lambda is a classic example of a protein that binds to its operator
      sites cooperatively. The C-terminal domain of the repressor mediates dimerization
      as well as a dimer-dimer interaction that results in the cooperative binding of
      two repressor dimers to adjacent operator sites. Here, we present the x-ray
      crystal structure of the lambda repressor C-terminal domain determined by
      multiwavelength anomalous diffraction. Remarkably, the interactions that mediate
      cooperativity are captured in the crystal, where two dimers associate about a 2
      fold axis of symmetry. Based on the structure and previous genetic and
      biochemical data, we present a model for the cooperative binding of two lambda
      repressor dimers at adjacent operator sites.

PMID- 10892751
TI  - They call it a smack.

PMID- 10892752
TI  - The refiguration of medical thought.

PMID- 10892753
TI  - The $64000 question in diabetes continues..

PMID- 10892754
TI  - Interferon plus chemotherapy for primary treatment of ovarian cancer.

PMID- 10892755
TI  - Challenge of reducing drug-related deaths.

PMID- 10892756
TI  - Jehovah's Witnesses' blood policy.

PMID- 10892757
TI  - Names to remember.

PMID- 10892758
TI  - Outcome at 1 year after an invasive compared with a non-invasive strategy in
      unstable coronary-artery disease: the FRISC II invasive randomised trial. FRISC
      II Investigators. Fast Revascularisation during Instability in Coronary artery
      disease.
AB  - BACKGROUND: The Fragmin and Fast Revascularisation during Instability in Coronary
      artery disease II trial (FRISC II) compared an early invasive with an early non
      invasive strategy in unstable coronary-artery disease. We report outcome at 1
      year. METHODS: 2457 patients were randomly assigned invasive or non-invasive
      treatment and 3 months of dalteparin or placebo. Complete information at 1 year
      was available for 1222 in the invasive group and 1234 in the non-invasive group.
      Analyses were by intention to treat. FINDINGS: Revascularisation was done within
      the first 10 days in 71% of the invasive group and 9% of the non-invasive group
      and within the first year in 78% and 43%. During the first year, 27 (2.2%)
      patients in the invasive group and 48 (3.9%) in the non-invasive group died (risk
      ratio 0.57 [95% CI 0.36-0.90], p=0.016). 105 (8.6%) versus 143 (11.6%) had
      myocardial infarction (0.74 [0.59-0.94], p=0.015). The composite of death or
      myocardial infarction occurred in 127 (10.4%) versus 174 (14.1%) patients (0.74
      [0.60-0.92], p=0.005). There were also reductions in readmission (451 [37%] vs
      704 [57%]; 0.67 [0.62-0.72]), and revascularisation after the initial admission
      (92 [7.5%] vs 383 [31%]; 0.24 [0.20-0.30]). The results did not interact with the
      dalteparin/placebo allocation. INTERPRETATION: After 1 year in 100 patients, an
      invasive strategy saves 1.7 lives, prevents 2.0 non-fatal myocardial infarctions
      and 20 readmissions, and provides earlier and better symptom relief at the cost
      of 15 more patients with coronary-artery bypass grafting and 21 more with
      percutaneous transluminal angioplasty. Therefore, an invasive approach should be
      the preferred strategy in patients with unstable coronary-artery disease and
      signs of ischaemia on electrocardiography or raised levels of biochemical markers
      of myocardial damage.

PMID- 10892759
TI  - Mortality among UK Gulf War veterans.
AB  - BACKGROUND: Armed forces personnel who served in the Gulf War report more current
      ill-health than those who were not deployed. There has been concern expressed
      that they may also experience higher mortality rates. METHODS: A retrospective
      cohort study was done including all 53462 UK Gulf War veterans (Gulf cohort) and
      a comparison group equivalent in size of personnel who were not deployed but
      matched for age, sex, rank, service, and level of fitness (Era cohort).
      Individuals were identified on central registers of the Office for National
      Statistics and information on death among cohort subjects, including cause of
      death, obtained. Follow-up extended from April 1, 1991 (the end of the Gulf War)
      until March 31, 1999. FINDINGS: There were 395 deaths among the Gulf cohort and
      378 deaths amongst the Era cohort (mortality rate ratio [MRR] 1.05, 95% CI 0.91
      1.21). Mortality from "external" causes was higher in the Gulf cohort (Gulf 254,
      Era 216; MRR 1.18 [0.98-1.42] while mortality from "disease-related" causes was
      lower (Gulf 122, Era 141; 0.87 [0.67-1.11]). The higher mortality rate from
      "external" causes in the Gulf cohort was principally due to higher mortality
      rates from accidents. There was, however, no excess of deaths recorded as suicide
      in the Gulf cohort. INTERPRETATION: This follow-up of veterans of the Gulf war
      has shown, 8 years after the end of the conflict, that although they have
      experienced higher mortality rates than a comparison cohort, the excess mortality
      rate is very small and does not approach statistical significance. The excess is
      related mainly to accidents rather than disease, a pattern that is consistent
      both with US veterans of the Gulf war and veterans from other conflicts.

PMID- 10892760
TI  - Classification of drug-resistant tuberculosis in an epidemic area.
AB  - BACKGROUND: Traditionally, patients with drug-resistant tuberculosis are
      classified as having acquired drug-resistant or primary drug-resistant disease on
      the basis of a history of previous tuberculosis treatment. Only cases of primary
      drug resistance are assumed to be due to transmission of drug-resistant strains.
      METHODS: This descriptive study of 63 patients with drug-resistant tuberculosis
      assessed the relative contribution of transmission of drug-resistant strains in a
      high-incidence community of Cape Town, South Africa, by restriction-fragment
      length polymorphism (RFLP). The RFLP results were compared with the results
      obtained by traditional classification methods. FINDINGS: According to RFLP
      definitions, 52% (33 cases) of drug-resistant tuberculosis was caused by
      transmission of a drug-resistant strain. The proportion of cases due to
      transmission was higher for multidrug-resistant (64%; 29 cases) than for single
      drug-resistant (no cases) tuberculosis. By the clinical classification, only 18
      (29%) patients were classified as having primary drug-resistant tuberculosis
      (implying transmission). The clinical classification was thus misleading in 25
      patients. INTERPRETATION: The term acquired drug resistance includes patients
      infected with strains that truly acquired drug resistance during treatment and
      patients who were initially infected with or reinfected with a drug-resistant
      strain. This definition could lead to misinterpretation of surveillance studies,
      incorrect evaluation of tuberculosis programmes, and delayed diagnosis and
      treatment of patients with multidrug-resistant disease. The clinical term
      acquired drug resistance should be replaced with the term "drug resistance in
      previously treated cases", which includes cases with drug resistance due to true
      acquisition as well as that due to transmitted drug-resistant strains.

PMID- 10892761
TI  - Effects of different doses in continuous veno-venous haemofiltration on outcomes
      of acute renal failure: a prospective randomised trial.
AB  - BACKGROUND: Continuous veno-venous haemofiltration is increasingly used to treat
      acute renal failure in critically ill patients, but a clear definition of an
      adequate treatment dose has not been established. We undertook a prospective
      randomised study of the impact different ultrafiltration doses in continuous
      renal replacement therapy on survival. METHODS: We enrolled 425 patients, with a
      mean age of 61 years, in intensive care who had acute renal failure. Patients
      were randomly assigned ultrafiltration at 20 mL h(-1) kg(-1) (group 1, n=146), 35
      mL h(-1) kg(-1) (group 2, n=139), or 45 mL h(-1) kg(-1) (group 3, n=140). The
      primary endpoint was survival at 15 days after stopping haemofiltration. We also
      assessed recovery of renal function and frequency of complications during
      treatment. Analysis was by intention to treat. RESULTS: Survival in group 1 was
      significantly lower than in groups 2 (p=0.0007) and 3 (p=0.0013). Survival in
      groups 2 and 3 did not differ significantly (p=0.87). Adjustment for possible
      confounding factors did not change the pattern of differences among the groups.
      Survivors in all groups had lower concentrations of blood urea nitrogen before
      continuous haemofiltration was started than non-survivors. 95%, 92%, and 90% of
      survivors in groups 1, 2, and 3, respectively, had full recovery of renal
      function. The frequency of complications was similarly low in all groups.
      INTERPRETATION: Mortality among these critically ill patients was high, but
      increase in the rate of ultrafiltration improved survival significantly. We
      recommend that ultrafiltration should be prescribed according to patient's
      bodyweight and should reach at least 35 mL h(-1) kg(-1).

PMID- 10892762
TI  - Immune reactivity to glutamic acid decarboxylase 65 in stiffman syndrome and type
      1 diabetes mellitus.
AB  - BACKGROUND: The immune response to an isoform of glutamic acid decarboxylase
      (GAD), GAD65, is associated with two clinically distinct diseases, stiff-man
      syndrome (SMS) and type 1 (insulin-dependent) diabetes mellitus. We sought to
      identify differences in the cellular and humoral immune responses to GAD in these
      two diseases. METHODS: We compared T-cell responses in 14 SMS patients with axial
      disease and 17 patients with type 1 diabetes. FINDINGS: Peripheral blood T cells
      of eight SMS patients recognised different immunodominant epitopes of GAD65
      compared with T cells from 17 patients with type 1 diabetes. GAD regions 81-171
      and 313-403 induced a dominant T-cell response in six of eight patients with SMS
      but in only one of 17 patients with type 1 diabetes (p=0.001). No SMS patients
      responded dominantly to GAD fragments 161-243 and 473-555 compared with ten
      patients with type 1 diabetes (p=0.008). GAD antibodies were detected in 11 of 14
      SMS patients (seven with diabetes) and 11 of 17 patients with type 1 diabetes;
      IgG1 was dominant in both groups. SMS patients, however, were more likely than
      patients with diabetes to have isotypes other than IgG1 (p=0.03), in particular,
      IgG4 or IgE isotypes, which were not detected in patients with type 1 diabetes
      (p=0.012). INTERPRETATION: Our findings indicate differences between patients
      with SMS and type 1 diabetes in cellular (epitope recognition) and humoral
      (isotype pattern) responses to GAD65. Thus the same autoantigen can elicit
      distinct immune responses in patients with SMS, even when associated with
      diabetes, compared with patients with type 1 diabetes.

PMID- 10892763
TI  - Choriocarcinoma and partial hydatidiform moles.
AB  - BACKGROUND: Partial hydatidiform moles (PMs) rarely require chemotherapy and have
      never previously been proven to transform into choriocarcinoma, the most
      malignant form of gestational trophoblastic disease (GTD). Consequently, some
      have questioned whether women with PMs need human chorionic gonadotropin (hCG)
      follow-up. Here, we investigate whether PMs can transform into choriocarcinomas.
      METHODS: Patients with a PM who developed a subsequent choriocarcinoma were
      identified from our GTD database. The histology of both PM and ensuing
      choriocarcinoma was reviewed and flow cytometry used to verify the triploid
      status of the PMs. To determine whether the choriocarcinoma arose from the PM,
      DNA from the PM and choriocarcinoma in each patient was compared using
      microsatellite polymorphisms. FINDINGS: Of the 3000 patients with PM, 15 required
      chemotherapy for persisting GTD. This was identified as choriocarcinoma in three
      cases. In one patient, the local pathologist could not differentiate between a PM
      or a hydropic abortion and neither central histological review nor hCG follow-up
      were obtained. This patient nearly died before the diagnosis of choriocarcinoma
      was made. Fortunately, the local pathologists correctly diagnosed PM in the two
      other patients who were then registered for hCG follow-up. Some months later, the
      hCG was rising and repeat uterine evacuation revealed choriocarcinoma. The PM was
      confirmed to be triploid in all three cases and genetic analysis showed that the
      subsequent choriocarcinomas contained identical single maternal and two paternal
      alleles at several independent loci. INTERPRETATION: Our results show that PMs
      can transform into choriocarcinoma. All patients with suspected PM should be
      reviewed centrally and, if confirmed, need hCG follow-up.

PMID- 10892764
TI  - Acute aphasia and hemiplegia during karate training.

PMID- 10892765
TI  - Recovery from chronic hepatitis C in long-term responders to ribavirin plus
      interferon alfa.
AB  - In 45 sustained responders to interferon alfa and ribavirin, we found long
      lasting elimination of hepatitis C virus RNA from serum and liver, together with
      histopathological improvement, suggesting complete recovery from chronic
      hepatitis C.

PMID- 10892766
TI  - Detection of hepatitis C virus in the semen of infected men.
AB  - We detected hepatitis C virus (HCV) RNA in the semen of one third of HCV viraemic
      men. Seminal viral loads were low, but the semen could be infectious and the role
      of sexual transmission in the spread of HCV infection should not be
      underestimated.

PMID- 10892767
TI  - How reliable is a vasectomy? Long-term follow-up of vasectomised men.
AB  - Around 42 million couples worldwide rely on vasectomy as a method of family
      planning. It is well recognised that a vasectomy can fall at any stage, and
      therefore warning couples of risk of failure forms an important part of the
      consent procedure.

PMID- 10892768
TI  - New dopaminergic neurons in Parkinson's disease striatum.
AB  - A new population of dopaminergic neurons has been identified in Parkinson's
      disease striatum. These neurons are sufficiently numerous to have an important
      effect on dopaminergic function in the striatum.

PMID- 10892769
TI  - Extracorporeal membrane oxygenation in pregnancy.
AB  - We describe the use of extracorporeal membrane oxygenation in pregnancy. There
      were no major complications, and the outcome was successful for mother and baby.

PMID- 10892770
TI  - "Working draft" of human genome completed.

PMID- 10892771
TI  - Artificial thymus can produce T-cells.

PMID- 10892773
TI  - Drug insurance for the elderly moves ahead in Congress.

PMID- 10892772
TI  - Proteomics: the next step after genomics?

PMID- 10892774
TI  - Germany halts tick-borne encephalitis vaccination.

PMID- 10892775
TI  - European clinical research scandal investigators question self-regulation.

PMID- 10892776
TI  - South Korean doctors end crippling strike.

PMID- 10892777
TI  - Breaking the silence: setting realistic priorities for AIDS control in less
      developed countries.
AB  - The AIDS pandemic is a human tragedy that is threatening development in the
      poorest countries. There is no cure or vaccine, but the tools to control the
      epidemic already exist. Nevertheless, there are few examples of national AIDS
      control programmes that have had an impact on the epidemic. We (an economist and
      a planner) attribute this to the reluctance of governments to confront AIDS and a
      failure to prioritise activities in the face of severe financial and
      administrative constraints. When implementation capacity is weak, expanding the
      number of activities may not improve programme effectiveness. Rather, by
      implementing a smaller, core set of the most cost-effective activities on a
      national scale, policymakers could have a huge effect on the overall epidemic in
      a sustained way and provide a foundation for expansion. We propose three core
      priorities for AIDS control in poor countries for prevention, treatment, and
      mitigation of the impact.

PMID- 10892778
TI  - Brown-Sequard and his syndrome.

PMID- 10892779
TI  - Map-making and myth-making in Broad Street: the London cholera epidemic, 1854.

PMID- 10892780
TI  - Treatment without consent: a medicolegal precedent.

PMID- 10892781
TI  - Gastro-oesophageal reflux disease.

PMID- 10892782
TI  - Gastro-oesophageal reflux disease.

PMID- 10892783
TI  - Gastro-oesophageal reflux disease.

PMID- 10892784
TI  - Gastro-oesophageal reflux disease.

PMID- 10892785
TI  - Gastro-oesophageal reflux disease.

PMID- 10892786
TI  - Gastro-oesophageal reflux disease.

PMID- 10892787
TI  - Heparin vs aspirin in acute ischaemic stroke.

PMID- 10892788
TI  - Vitamin D deficiency and tuberculosis.

PMID- 10892789
TI  - Vitamin D deficiency and tuberculosis.

PMID- 10892790
TI  - Vitamin D deficiency and tuberculosis.

PMID- 10892791
TI  - Allergy to icodextrin.

PMID- 10892792
TI  - QTc and psychotropic drugs.

PMID- 10892793
TI  - Social networks and dementia.

PMID- 10892794
TI  - Social networks and dementia.

PMID- 10892795
TI  - Creating safety with the social model of birth.

PMID- 10892796
TI  - Helping children in Iraq.

PMID- 10892797
TI  - The Nobel chronicles. 1995: Edward B Lewis (b 1918), Christiane Nusslein-Volhard
      (b 1942), and Eric Francis Wieschaus (b 1947).

PMID- 10892798
TI  - The 1.9 A crystal structure of Escherichia coli MurG, a membrane-associated
      glycosyltransferase involved in peptidoglycan biosynthesis.
AB  - The 1.9 A X-ray structure of a membrane-associated glycosyltransferase involved
      in peptidoglycan biosynthesis is reported. This enzyme, MurG, contains two
      alpha/beta open sheet domains separated by a deep cleft. Structural analysis
      suggests that the C-terminal domain contains the UDP-GlcNAc binding site while
      the N-terminal domain contains the acceptor binding site and likely membrane
      association site. Combined with sequence data from other MurG homologs, this
      structure provides insight into the residues that are important in substrate
      binding and catalysis. We have also noted that a conserved region found in many
      UDP-sugar transferases maps to a beta/alpha/beta/alpha supersecondary structural
      motif in the donor binding region of MurG, an observation that may be helpful in
      glycosyltransferase structure prediction. The identification of a conserved
      structural motif involved in donor binding in different UDP-sugar transferases
      also suggests that it may be possible to identify--and perhaps alter--the
      residues that help determine donor specificity.

PMID- 10892799
TI  - Stereoselectivity of Pseudomonas cepacia lipase toward secondary alcohols: a
      quantitative model.
AB  - The lipase from Pseudomonas cepacia represents a widely applied catalyst for
      highly enantioselective resolution of chiral secondary alcohols. While its
      stereopreference is determined predominantly by the substrate structure,
      stereoselectivity depends on atomic details of interactions between substrate and
      lipase. Thirty secondary alcohols with published E values using P. cepacia lipase
      in hydrolysis or esterification reactions were selected, and models of their
      octanoic acid esters were docked to the open conformation of P. cepacia lipase.
      The two enantiomers of 27 substrates bound preferentially in either of two
      binding modes: the fast-reacting enantiomer in a productive mode and the slow
      reacting enantiomer in a nonproductive mode. Nonproductive mode of fast-reacting
      enantiomers was prohibited by repulsive interactions. For the slow-reacting
      enantiomers in the productive binding mode, the substrate pushes the active site
      histidine away from its proper orientation, and the distance d(H(N epsilon) -
      O(alc)) between the histidine side chain and the alcohol oxygen increases, d(H(N
      epsilon) - O(alc)) was correlated to experimentally observed enantioselectivity:
      in substrates for which P. cepacia lipase has high enantioselectivity (E > 100),
      d(H(N epsilon) - O(alc)) is >2.2 A for slow-reacting enantiomers, thus preventing
      efficient catalysis of this enantiomer. In substrates of low enantioselectivity
      (E < 20), the distance d(H(N epsilon) - O(alc)) is less than 2.0 A, and slow- and
      fast-reacting enantiomers are catalyzed at similar rates. For substrates of
      medium enantioselectivity (20 < E < 100), d(H(N epsilon) - O(alc)) is around 2.1
      A. This simple model can be applied to predict enantioselectivity of P. cepacia
      lipase toward a broad range of secondary alcohols.

PMID- 10892800
TI  - Three-dimensional structures of Drosophila melanogaster acetylcholinesterase and
      of its complexes with two potent inhibitors.
AB  - We have crystallized Drosophila melanogaster acetylcholinesterase and solved the
      structure of the native enzyme and of its complexes with two potent reversible
      inhibitors, 1,2,3,4-tetrahydro-N-(phenylmethyl)-9-acridinamine and 1,2,3,4
      tetrahydro-N-(3-iodophenyl-methyl)-9-acridinamine--all three at 2.7 A resolution.
      The refined structure of D. melanogaster acetylcholinesterase is similar to that
      of vertebrate acetylcholinesterases, for example, human, mouse, and fish, in its
      overall fold, charge distribution, and deep active-site gorge, but some of the
      surface loops deviate by up to 8 A from their position in the vertebrate
      structures, and the C-terminal helix is shifted substantially. The active-site
      gorge of the insect enzyme is significantly narrower than that of Torpedo
      californica AChE, and its trajectory is shifted several angstroms. The volume of
      the lower part of the gorge of the insect enzyme is approximately 50% of that of
      the vertebrate enzyme. Upon binding of either of the two inhibitors, nine
      aromatic side chains within the active-site gorge change their conformation so as
      to interact with the inhibitors. Some differences in activity and specificity
      between the insect and vertebrate enzymes can be explained by comparison of their
      three-dimensional structures.

PMID- 10892802
TI  - Conformational stability changes of the amino terminal domain of enzyme I of the
      Escherichia coli phosphoenolpyruvate: sugar phosphotransferase system produced by
      substituting alanine or glutamate for the active-site histidine 189: implications
      for phosphorylation effects.
AB  - The amino terminal domain of enzyme I (residues 1-258 + Arg; EIN) and full length
      enzyme I (575 residues; EI) harboring active-site mutations (H189E, expected to
      have properties of phosphorylated forms, and H189A) have been produced by protein
      bioengineering. Differential scanning calorimetry (DSC) and temperature-induced
      changes in ellipticity at 222 nm for monomeric wild-type and mutant EIN proteins
      indicate two-state unfolding. For EIN proteins in 10 mM K-phosphate (and 100 mM
      KCl) at pH 7.5, deltaH approximately 140 +/- 10 (160) kcal mol(-1) and deltaCp
      approximately 2.7 (3.3) kcal K(-1) mol(-1). Transition temperatures (Tm) are 57
      (59), 55 (58), and 53 (56) degrees C for wild-type, H189A, and H189E forms of
      EIN, respectively. The order of conformational stability for dephospho-His189,
      phospho-His189, and H189 substitutions of EIN at pH 7.5 is: His > Ala > Glu > His
      PO3(2-) due to differences in conformational entropy. Although H189E mutants have
      decreased Tm values for overall unfolding the amino terminal domain, a small
      segment of structure (3 to 12%) is stabilized (Tm approximately 66-68 degrees C).
      This possibly arises from an ion pair interaction between the gamma-carboxyl of
      Glu189 and the epsilon-amino group of Lys69 in the docking region for the
      histidine-containing phosphocarrier protein HPr. However, the binding of HPr to
      wild-type and active-site mutants of EIN and EI is temperature-independent
      (entropically controlled) with about the same affinity constant at pH 7.5: K(A)'
      = 3 +/- 1 x 10(5) M(-1) for EIN and approximately 1.2 x 10(5) M(-1) for EI.

PMID- 10892801
TI  - A new model for 20-hydroxyecdysone and dibenzoylhydrazine binding: a homology
      modeling and docking approach.
AB  - The ecdysone receptor (ECR), a nuclear transcription factor controlling insect
      development, is a novel target for insecticides such as dibenzoylhydrazines with
      low environmental and toxicological impacts. To understand the high selectivity
      of such synthetic molecules toward ECR, two homology models of the Chironomus
      tentans ECR ligand-binding domain (LDB) have been constructed by taking as
      templates the known LBD crystal structures of the retinoic acid and vitamin D
      receptors. Docking of 20-hydroxyecdysone (20E) and dibenzoylhydrazines to the
      receptor suggests a novel superposition of the natural and synthetic molecules;
      the N-tert-butyl substituent of the dibenzoylhydrazines extends significantly
      beyond the 20E volume. Our ECR-LBD protein models rationalize how 20E and
      dibenzoylhydrazines interact with the ligand-binding pocket. The homology model
      complexes provide new insights that can be exploited in the rational design of
      new environmentally safe insecticides.

PMID- 10892804
TI  - Prediction of amino acid sequence from structure.
AB  - We have developed a method for the prediction of an amino acid sequence that is
      compatible with a three-dimensional backbone structure. Using only a backbone
      structure of a protein as input, the algorithm is capable of designing sequences
      that closely resemble natural members of the protein family to which the template
      structure belongs. In general, the predicted sequences are shown to have multiple
      sequence profile scores that are dramatically higher than those of random
      sequences, and sometimes better than some of the natural sequences that make up
      the superfamily. As anticipated, highly conserved but poorly predicted residues
      are often those that contribute to the functional rather than structural
      properties of the protein. Overall, our analysis suggests that statistical
      profile scores of designed sequences are a novel and valuable figure of merit for
      assessing and improving protein design algorithms.

PMID- 10892803
TI  - Conformational behavior of ionic self-complementary peptides.
AB  - Several de novo designed ionic peptides that are able to undergo conformational
      change under the influence of temperature and pH were studied. These peptides
      have two distinct surfaces with regular repeats of alternating hydrophilic and
      hydrophobic side chains. This permits extensive ionic and hydrophobic
      interactions resulting in the formation of stable beta-sheet assemblies. The
      other defining characteristic of this type of peptide is a cluster of negatively
      charged aspartic or glutamic acid residues located toward the N-terminus and
      positively charged arginine or lysine residues located toward the C-terminus.
      This arrangement of charge balances the alpha-helical dipole moment (C --> N),
      resulting in a strong tendency to form stable alpha-helices as well. Therefore,
      these peptides can form both stable alpha-helices and beta-sheets. They are also
      able to undergo abrupt structural transformations between these structures
      induced by temperature and pH changes. The amino acid sequence of these peptides
      permits both stable beta-sheet and alpha-helix formation, resulting in a balance
      between these two forms as governed by the environment. Some segments in proteins
      may also undergo conformational changes in response to environmental changes.
      Analyzing the plasticity and dynamics of this type of peptide may provide insight
      into amyloid formation. Since these peptides have dynamic secondary structure,
      they will serve to refine our general understanding of protein structure.

PMID- 10892805
TI  - Tumor suppressor INK4: refinement of p16INK4A structure and determination of
      p15INK4B structure by comparative modeling and NMR data.
AB  - Within the tumor suppressor protein INK4 (inhibitor of cyclin-dependent kinase 4)
      family, p15INK4B is the smallest and the only one whose structure has not been
      determined previously, probably due to the protein's conformational flexibility
      and instability. In this work, multidimensional NMR studies were performed on
      this protein. The first tertiary structure was built by comparative modeling with
      p16INK4A as the template, followed by restrained energy minimization with NMR
      constraints (NOE and H-bonds). For this purpose, the solution structure of
      pl6INK4A, whose quality was also limited by similar problems, was refined with
      additional NMR experiments conducted on an 800 MHz spectrometer and by structure
      based iterative NOE assignments. The nonhelical regions showed major improvement
      with root-mean-square deviation (RMSD) improved from 1.23 to 0.68 A for backbone
      heavy atoms. The completion of p15INK4B coupled with refinement of p16INK4A made
      it possible to compare the structures of the four INK4 members in depth, and to
      compare the structures of p16INK4A in the free form and in the p16INK4A-CDK6
      complex. This is an important step toward a comprehensive understanding of the
      precise functional roles of each INK4 member.

PMID- 10892806
TI  - Change in backbone torsion angle distribution on protein folding.
AB  - Understanding protein folding requires the determination of the configurational
      space accessible to the protein at different stages in folding. Here, computer
      simulation analysis of small angle neutron scattering results is used to probe
      the change in the distribution of configurations on strong denaturation of a
      globular protein, phosphoglycerate kinase, in 4 M guanidine hydrochloride
      solution. To do this atomic-detail ensembles of the unfolded protein chain are
      modeled and their scattering profiles compared with the experiment. The local
      conformational statistics are found to strongly influence the experimental
      intensity at scattering vectors between 0.05 and 0.3 A(-1). Denaturation leads to
      a reduction in the protein atom-pair distance distribution function over the
      approximately 3-15 A region that is associated with a quantifiable shift in the
      backbone torsional angle (phi, psi) distribution toward the beta region of the
      Ramachandran plot.

PMID- 10892807
TI  - Characterization and molecular basis of the oligomeric structure of HIV-1 nef
      protein.
AB  - The Nef protein of human immunodeficiency virus type I (HIV-1) is an important
      determinant for the onset of AIDS disease. The self-association properties of HIV
      1 Nef are analyzed by chemical cross-linking, dynamic light scattering,
      equilibrium analytical ultracentrifugation, and NMR spectroscopy. The
      experimental data show that the HIV-1 Nef core domain forms stable homo-dimers
      and trimers in solution, but not higher oligomers. These Nef homomers are not
      covalently linked by disulfide bridges, and the equilibrium between these forms
      is dependent on the Nef concentration. We further provide the molecular basis for
      the Nef core dimers and trimers obtained by analysis of crystallographic models.
      Oligomerization of biological polypeptides is a common tool used to trigger
      events in cellular signaling and endocytosis, both of which are targeted by Nef.
      The quaternary structure of Nef may be of physiological importance and may help
      to connect its cellular targets or to increase affinity of the viral molecule for
      its ligands. The herein described models for Nef dimers and trimers will allow
      further mutational studies to elucidate their role in vivo. These results provide
      novel insight into the structural and functional relationships of this important
      viral protein. Moreover, the oligomer interface may represent a novel target for
      the design of antiviral agents.

PMID- 10892808
TI  - Thermal denaturation pathway of starch phosphorylase from Corynebacterium
      callunae: oxyanion binding provides the glue that efficiently stabilizes the
      dimer structure of the protein.
AB  - Starch phosphorylase from Corynebacterium callunae is a dimeric protein in which
      each mol of 90 kDa subunit contains 1 mol pyridoxal 5'-phosphate as an active
      site cofactor. To determine the mechanism by which phosphate or sulfate ions
      bring about a greater than 500-fold stabilization against irreversible
      inactivation at elevated temperatures (> or = 50 degrees C), enzyme/oxyanion
      interactions and their role during thermal denaturation of phosphorylase have
      been studied. By binding to a protein site distinguishable from the catalytic
      site with dissociation constants of Ksulfate = 4.5 mM and Kphosphate
      approximately 16 mM, dianionic oxyanions induce formation of a more compact
      structure of phosphorylase, manifested by (a) an increase by about 5% in the
      relative composition of the alpha-helical secondary structure, (b) reduced 1H/2H
      exchange, and (c) protection of a cofactor fluorescence against quenching by
      iodide. Irreversible loss of enzyme activity is triggered by the release into
      solution of pyridoxal 5'-phosphate, and results from subsequent intermolecular
      aggregation driven by hydrophobic interactions between phosphorylase subunits
      that display a temperature-dependent degree of melting of secondary structure. By
      specifically increasing the stability of the dimer structure of phosphorylase
      (probably due to tightened intersubunit contacts), phosphate, and sulfate, this
      indirectly (1) preserves a functional active site up to approximately 50 degrees
      C, and (2) stabilizes the covalent protein cofactor linkage up to approximately
      70 degrees C. The effect on thermostability shows a sigmoidal and saturatable
      dependence on the concentration of phosphate, with an apparent binding constant
      at 50 degrees C of approximately 25 mM. The extra stability conferred by oxyanion
      ligand binding to starch phosphorylase is expressed as a dramatic shift of the
      entire denaturation pathway to a approximately 20 degrees C higher value on the
      temperature scale.

PMID- 10892809
TI  - Cascaded multiple classifiers for secondary structure prediction.
AB  - We describe a new classifier for protein secondary structure prediction that is
      formed by cascading together different types of classifiers using neural networks
      and linear discrimination. The new classifier achieves an accuracy of 76.7%
      (assessed by a rigorous full Jack-knife procedure) on a new nonredundant dataset
      of 496 nonhomologous sequences (obtained from G.J. Barton and J.A. Cuff). This
      database was especially designed to train and test protein secondary structure
      prediction methods, and it uses a more stringent definition of homologous
      sequence than in previous studies. We show that it is possible to design
      classifiers that can highly discriminate the three classes (H, E, C) with an
      accuracy of up to 78% for beta-strands, using only a local window and resampling
      techniques. This indicates that the importance of long-range interactions for the
      prediction of beta-strands has been probably previously overestimated.

PMID- 10892810
TI  - The role of backbone conformational heat capacity in protein stability:
      temperature dependent dynamics of the B1 domain of Streptococcal protein G.
AB  - The contributions of backbone NH group dynamics to the conformational heat
      capacity of the B1 domain of Streptococcal protein G have been estimated from the
      temperature dependence of 15N NMR-derived order parameters. Longitudinal (R1) and
      transverse (R2) relaxation rates, transverse cross-relaxation rates (eta(xy)),
      and steady state [1H]-15N nuclear Overhauser effects were measured at
      temperatures of 0, 10, 20, 30, 40, and 50 degrees C for 89-100% of the backbone
      secondary amide nitrogen nuclei in the B1 domain. The ratio R2/eta(xy) was used
      to identify nuclei for which conformational exchange makes a significant
      contribution to R2. Relaxation data were fit to the extended model-free dynamics
      formalism, incorporating an axially symmetric molecular rotational diffusion
      tensor. The temperature dependence of the order parameter (S2) was used to
      calculate the contribution of each NH group to conformational heat capacity (Cp)
      and a characteristic temperature (T*), representing the density of conformational
      energy states accessible to each NH group. The heat capacities of the secondary
      structure regions of the B1 domain are significantly higher than those of
      comparable regions of other proteins, whereas the heat capacities of less
      structured regions are similar to those in other proteins. The higher local heat
      capacities are estimated to contribute up to approximately 0.8 kJ/mol K to the
      total heat capacity of the B1 domain, without which the denaturation temperature
      would be approximately 9 degrees C lower (78 degrees C rather than 87 degrees C).
      Thus, variation of backbone conformational heat capacity of native proteins may
      be a novel mechanism that contributes to high temperature stabilization of
      proteins.

PMID- 10892811
TI  - Unfolding and refolding of cytochrome c driven by the interaction with lipid
      micelles.
AB  - Binding of native cyt c to L-PG micelles leads to a partially unfolded
      conformation of cyt c. This micelle-bound state has no stable tertiary structure,
      but remains as alpha-helical as native cyt c in solution. In contrast, binding of
      the acid-unfolded cyt c to L-PG micelles induces folding of the polypeptide,
      resulting in a similar helical state to that originated from the binding of
      native cyt c to L-PG micelles. Far-ultraviolet (UV) circular dichroism (CD)
      spectra showed that this common micelle-associated helical state (HL) has a
      native-like alpha-helix content, but is highly expanded without a tightly packed
      hydrophobic core, as revealed by tryptophan fluorescence, near-UV, and Soret CD
      spectroscopy. The kinetics of the interaction of native and acid-unfolded cyt c
      was investigated by stopped-flow tryptophan fluorescence. Formation of H(L) from
      the native state requires the disruption of the tightly packed hydrophobic core
      in the native protein. This micelle-induced unfolding of cyt c occurs at a rate
      approximately 0.1 s(-1), which is remarkably faster in the lipid environment
      compared with the expected rate of unfolding in solution. Refolding of acid
      unfolded cyt c with L-PG micelles involves an early highly helical collapsed
      state formed during the burst phase (<3 ms), and the observed main kinetic event
      reports on the opening of this early compact intermediate prior to insertion into
      the lipid micelle.

PMID- 10892812
TI  - Amino acid repeat patterns in protein sequences: their diversity and structural
      functional implications.
AB  - All the protein sequences from SWISS-PROT database were analyzed for occurrence
      of single amino acid repeats, tandem oligo-peptide repeats, and periodically
      conserved amino acids. Single amino acid repeats of glutamine, serine, glutamic
      acid, glycine, and alanine seem to be tolerated to a considerable extent in many
      proteins. Tandem oligo-peptide repeats of different types with varying levels of
      conservation were detected in several proteins and found to be conspicuous,
      particularly in structural and cell surface proteins. It appears that repeated
      sequence patterns may be a mechanism that provides regular arrays of spatial and
      functional groups, useful for structural packing or for one to one interactions
      with target molecules. To facilitate further explorations, a database of Tandem
      Repeats in Protein Sequences (TRIPS) has been developed and is available at URL:
      http://www.ncl-india.org/trips.

PMID- 10892813
TI  - Overall rotational diffusion and internal mobility in domain II of protein G from
      Streptococcus determined from 15N relaxation data.
AB  - The backbone dynamics and overall tumbling of protein G have been investigated
      using 15N relaxation. Comparison of measured R2/R1 relaxation rate ratios with
      known three-dimensional coordinates of the protein show that the rotational
      diffusion tensor is significantly asymmetric, exhibiting a prolate axial
      symmetry. Extensive Monte Carlo simulations have been used to estimate the
      uncertainty due to experimental error in the relaxation rates to be
      D(parallel)/D(perpendicular) = 1.68 +/- 0.08, while the dispersion in the NMR
      ensemble leads to a variation of D(parallel)/D(perpendicular) = 1.65 +/- 0.03.
      Incorporation of this tensorial description into a Lipari-Szabo type analysis of
      internal motion has allowed us to accurately describe the local dynamics of the
      molecule. This analysis differs from an earlier study where the overall
      rotational diffusion was described by a spherical top. In this previous analysis,
      exchange parameters were fitted to many of the residues in the alpha helix. This
      was interpreted as reflecting a small motion of the alpha helix with respect to
      the beta sheet. We propose that the differential relaxation properties of this
      helix compared to the beta sheet are due to the near-orthogonality of the NH
      vectors in the two structural motifs with respect to the unique axis of the
      diffusion tensor. Our analysis shows that when anisotropic rotational diffusion
      is taken into account NH vectors in these structural motifs appear to be equally
      rigid. This study underlines the importance of a correct description of the
      rotational diffusion tensor if internal motion is to be accurately investigated.

PMID- 10892814
TI  - Productive and nonproductive binding to ribonuclease A: X-ray structure of two
      complexes with uridylyl(2',5')guanosine.
AB  - Guanine-containing mono- and dinucleotides bind to the active site of
      ribonuclease A in a nonproductive mode (retro-binding) (Aguilar CF, Thomas PJ,
      Mills A, Moss DS, Palmer RA. 1992. J Mol Biol 224:265-267). Guanine binds to the
      highly specific pyrimidine site by forming hydrogen bonds with Thr45 and with the
      sulfate anion located in the P1 site. To investigate the influence of the anion
      present in the P1 site on retro-binding, we determined the structure of two new
      complexes of RNase A with uridylyl(2',5')guanosine obtained by soaking two
      different forms of pre-grown RNase A crystals. In one case, RNase A was
      crystallized without removing the sulfate anion strongly bound to the active
      site; in the other, the protein was first equilibrated with a basic solution to
      displace the anion from the P1 site. The X-ray structures of the complexes with
      and without sulfate in P1 were refined using diffraction data up to 1.8 A (R
      factor 0.192) and 2.0 A (R-factor 0.178), respectively. The binding mode of the
      substrate analogue to the protein differs markedly in the two complexes. When the
      sulfate is located in P1, we observe retro-binding; whereas when the anion is
      removed from the active site, the uridine is productively bound at the B1 site.
      In the productive complex, the electron density is very well defined for the
      uridine moiety, whereas the downstream guanine is disordered. This finding
      indicates that the interactions of guanine in the B2 site are rather weak and
      that this site is essentially adenine preferring. In this crystal form, there are
      two molecules per asymmetric unit, and due to crystal packing, only the active
      site of one molecule is accessible to the ligand. Thus, in the same crystal we
      have a ligand-bound and a ligand-free RNase A molecule. The comparison of these
      two structures furnishes a detailed and reliable picture of the structural
      alterations induced by the binding of the substrate. These results provide
      structural information to support the hypotheses on the role of RNase A active
      site residues that have recently emerged from site-directed mutagenesis studies.

PMID- 10892815
TI  - Dual coenzyme specificity of Archaeoglobus fulgidus HMG-CoA reductase.
AB  - Comparison of the inferred amino acid sequence of orf AF1736 of Archaeoglobus
      fulgidus to that of Pseudomonas mevalonii HMG-CoA reductase suggested that AF1736
      might encode a Class II HMG-CoA reductase. Following polymerase chain reaction
      based cloning of AF1736 from A. fulgidus genomic DNA and expression in
      Escherichia coli, the encoded enzyme was purified to apparent homogeneity and its
      enzymic properties were determined. Activity was optimal at 85 degrees C, deltaHa
      was 54 kJ/mol, and the statin drug mevinolin inhibited competitively with HMG-CoA
      (Ki 180 microM). Protonated forms of His390 and Lys277, the apparent cognates of
      the active site histidine and lysine of the P. mevalonii enzyme, appear essential
      for activity. The mechanism proposed for catalysis of P. mevalonii HMG-CoA
      reductase thus appears valid for A. fulgidus HMG-CoA reductase. Unlike any other
      HMG-CoA reductase, the A. fulgidus enzyme exhibits dual coenzyme specificity. pH
      activity profiles for all four reactions revealed that optimal activity using
      NADP(H) occurred at a pH from 1 to 3 units more acidic than that observed using
      NAD(H). Kinetic parameters were therefore determined for all substrates for all
      four catalyzed reactions using either NAD(H) or NADP(H). NADPH and NADH compete
      for occupancy of a common site. k(cat)[NAD(H)]/k(cat)[NADP(H)] varied from unity
      to under 70 for the four reactions, indicative of slight preference for NAD(H).
      The results indicate the importance of the protonated status of active site
      residues His390 and Lys277, shown by altered K(M) and k(cat) values, and indicate
      that NAD(H) and NADP(H) have comparable affinity for the same site.

PMID- 10892816
TI  - Molecular simulation study of cooperativity in hydrophobic association.
AB  - To investigate the cooperativity of hydrophobic interactions, the potential of
      mean force of two- and three-molecule methane clusters in water was determined by
      molecular dynamics simulations using two methods: umbrella-sampling with the
      weighted histogram analysis method and thermodynamic integration. Two water
      models, TIP3P and TIP4P, were used, while each methane molecule was modeled as a
      united atom. It was found that the three-body potential of mean force is not
      additive, i.e., it cannot be calculated as a sum of two-body contributions, but
      requires an additional three-body cooperative term. The cooperative term, which
      amounts to only about 10% of the total hydrophobic association free energy, was
      found to increase the strength of hydrophobic association; this finding differs
      from the results of earlier Monte Carlo studies with the free energy perturbation
      method of Rank and Baker (1997). As in the work of Rank and Baker, the solvent
      contribution to the potential of mean force was found to be well approximated by
      the molecular surface of two methane molecules. Moreover, we also found that the
      cooperative term is well represented by the difference between the molecular
      surface of the three-methane cluster and those of all three pairs of methane
      molecules. In addition, it was found that, while there is a cooperative
      contribution to the hydrophobic association free energy albeit a small one, the
      errors associated with the use of pairwise potentials are comparable to or larger
      than this contribution.

PMID- 10892817
TI  - Influence of the C-terminus of the glycophorin A transmembrane fragment on the
      dimerization process.
AB  - The monomer-dimer equilibrium of the glycophorin A (GpA) transmembrane (TM)
      fragment has been used as a model system to investigate the amino acid sequence
      requirements that permit an appropriate helix-helix packing in a membrane-mimetic
      environment. In particular, we have focused on a region of the helix where no
      crucial residues for packing have been yet reported. Various deletion and
      replacement mutants in the C-terminal region of the TM fragment showed that the
      distance between the dimerization motif and the flanking charged residues from
      the cytoplasmic side of the protein is important for helix packing. Furthermore,
      selected GpA mutants have been used to illustrate the rearrangement of TM
      fragments that takes place when leucine repeats are introduced in such protein
      segments. We also show that secondary structure of GpA derivatives was
      independent from dimerization, in agreement with the two-stage model for membrane
      protein folding and oligomerization.

PMID- 10892818
TI  - Assisted folding of D-glyceraldehyde-3-phosphate dehydrogenase by trigger factor.
AB  - The Escherichia coli trigger factor is a peptidyl-prolyl cis-trans isomerase that
      catalyzes proline-limited protein folding extremely well. Here, refolding of D
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the presence of trigger
      factor was investigated. The regain of activity of GAPDH was markedly increased
      by trigger factor after either long- or short-term denaturation, and detectable
      aggregation of GAPDH intermediates was prevented. In both cases, time courses of
      refolding of GAPDH were decelerated by trigger factor. The reactivation yield of
      GAPDH showed a slow down-turn when molar ratios of trigger factor to GAPDH were
      above 5, due to tight binding between trigger factor and GAPDH intermediates.
      Such inactive bound GAPDH could be partially rescued from trigger factor by
      addition of reduced alphaLA as competitor, by further diluting the refolding
      mixture, or by disrupting hydrophobic interactions in the complexes. A model for
      trigger factor assisted refolding of GAPDH is proposed. We also suggest that
      assisted refolding of GAPDH is due mainly to the chaperone function of trigger
      factor.

PMID- 10892819
TI  - Geographic, racial and ethnic disparities in heart disease mortality among women.

PMID- 10892820
TI  - Familial resemblance for coronary heart disease risk: the HERITAGE Family Study.
AB  - The objective of this study was to quantify familial resemblance for coronary
      heart disease risk in 260 Black and 427 White participants in the HERITAGE Family
      Study. Coronary heart disease risk was estimated using a coronary heart disease
      risk index (CHDRI) computed from the revised Framingham Heart Study algorithm,
      based on age, LDL-cholesterol, HDL-cholesterol, blood pressure, diabetes, and
      smoking status. Using a familial correlation model to test hypotheses regarding
      familial aggregation, significant familial resemblance was detected in both
      Blacks and Whites. There were significant sibling correlations in both Blacks and
      Whites, while spouse correlations were significant only in the White sample. The
      maximal heritabilities, which have to be interpreted cautiously in light of
      negligible parent-offspring correlations, were 34% and 53% in Whites and Blacks,
      respectively. Thus, the maximal heritability, which includes both genetic and non
      genetic sources of variation, is higher in Blacks than Whites, and explains a
      significant proportion of the total phenotypic variance. The results indicate
      that risk of coronary heart disease runs along family lines, and common
      environmental effects are important in explaining the observed familial
      resemblance.

PMID- 10892821
TI  - Cultural identity and health lifestyles among African Americans: a new direction
      for health intervention research?
AB  - OBJECTIVES: To assess associations of cultural and personal identity variables
      with socioeconomic status (SES) and health lifestyle in African Americans.
      DESIGN: Cross-sectional. METHODS: A questionnaire administered to 333 African
      Americans, ages 40-70 years, at enrollment in a nutrition education study
      assessed: African-American cultural identity (15 items scored 1 [low] to 4
      [high]); reference group (two questions about perceived success in the Black or
      White way of life-scored as bi-cultural if "yes" to both); personal identity (4
      items on: self-concept as attractive, self-confident, satisfied and friendly
      scored 1 [no/not sure] or 2 [yes]); and selected demographic and lifestyle
      variables. RESULTS: Cultural identity factors reflecting participation in and
      belonging to African-American culture and bi-cultural reference group were
      related to higher SES, lower fat diets, not smoking, current drinking, and higher
      leisure time physical activity (cultural identity only), particularly in women
      (P<.001 to P = .06). Associations of cultural identity with physical activity and
      of bi-cultural reference group with low-fat eating and not smoking (females)
      remained significant at P<.05 after adjustment for SES. CONCLUSIONS: A greater
      emphasis is needed on aspects of cultural identity that are positively related to
      health lifestyles as distinct from aspects that might act as barriers.

PMID- 10892822
TI  - An educational intervention for hypertension management in older African
      Americans.
AB  - OBJECTIVE: The purpose of this study was to assess the efficacy of a
      telecommunications approach to hypertension education. METHODS: Participants (N =
      83) were randomly assigned to the experimental and control groups. Experimental
      group participants received spiritual and hypertension-related messages via
      programmed telephone calls, and the control group participants received spiritual
      messages only. Both the experimental and control group participants received the
      following: printed material on hypertension-related information and regular home
      visits from a health educator to conduct pre-test and post-test assessments of
      hypertension knowledge, pill counts, and blood pressure readings. RESULTS: There
      were no statistically significant improvements in hypertension knowledge. By week
      4 of the intervention, there was a statistically significant decrease in systolic
      and diastolic blood pressure for both groups. However, there were no differences
      between the experimental and control groups. DISCUSSION: There was no evidence
      that the telecommunications approach improved older African Americans'
      understanding of hypertension or its management.

PMID- 10892823
TI  - Relationship of alcohol and illicit drug use with high blood pressure care and
      control among urban hypertensive Black men.
AB  - OBJECTIVE: To examine the relationships among alcohol and illicit drug use and
      high blood pressure (HBP) care and control. DESIGN: Baseline cross-sectional data
      from an ongoing clinical trial evaluating the effectiveness of a HBP care program
      was utilized. METHODS: Data collected at baseline on 309 urban hypertensive Black
      men, aged 18-54, included: socio-demographics, health status, HBP care behaviors,
      alcohol and illicit drug use, urine screen for illicit drug use, and blood
      pressure (BP). RESULTS: Men using alcohol and illicit drugs were less likely to
      report having medical insurance, having a doctor for HBP care, engaging in
      critical patient behaviors for HBP control, being on HBP medications, and
      compliance with HBP medication regimen. Alcohol and illicit drug users were more
      likely to eat high fat/high salt foods and significantly more likely to smoke
      cigarettes. In comparison to abstainers, men who used both alcohol and illicit
      drugs were significantly more likely to have uncontrolled BP and higher systolic
      blood pressure (SBP). CONCLUSIONS: Alcohol and illicit drug use were negatively
      associated with HBP care behaviors. Thus, BP was poorly controlled in this group
      of alcohol and illicit drug users. Screening, counseling, and treatment for
      alcohol and illicit drug use should be essential components in comprehensive HBP
      care.

PMID- 10892824
TI  - Body image and weight concerns among Southwestern American Indian preadolescent
      schoolchildren.
AB  - This study was undertaken to determine whether perceptions about body image and
      size vary by body mass index (BMI) and demographic factors among American Indian
      children in the Southwestern United States. We surveyed 1,996 American Indian
      schoolchildren in the fifth grade (mean age 10.5 +/- 0.7 years) at eleven rural
      elementary schools. Heights and weights were measured using standard protocol.
      Multiple linear regression models were developed for preferred body shape,
      desired body shape, and body satisfaction to determine association with
      demographic and physical factors. Results from multiple linear regression
      modeling indicated that BMI and gender influence body satisfaction, with heavier
      children and girls being less satisfied with their bodies (P<.001 and P<.05,
      respectively). Geographic isolation and lack of amenities in the home did not
      appear to affect body satisfaction or messages from others about being too fat or
      thin; however, geographically isolated students were more likely to choose a
      larger body shape as best looking. Girls of appropriate weight were 2.2 times
      more likely than boys to have been told they were too fat. Sixty-one percent of
      all students surveyed had tried to lose weight. These findings, although similar
      to those for non-Hispanic Whites of the same age, are contrary to prevailing
      ideas that American Indians value obesity. In fact, we observed a high level of
      body dissatisfaction among children of appropriate weight, particularly girls,
      and prevalent dieting across all weight categories and both genders.

PMID- 10892825
TI  - Racial discrimination and cigarette smoking among Blacks: findings from two
      studies.
AB  - We present the first studies to explore the relationship between racial
      discrimination and cigarette smoking among Blacks. One hundred fifty-three (Study
      1) and 300 (Study 2) Black adults completed a survey on their experiences with
      discrimination and their smoking. Logistic regressions revealed that racial
      discrimination was the best predictor of smoking among Blacks in both studies,
      and was a better predictor than status variables. Smoking prevalence rates for
      Blacks who experience frequent vs infrequent discrimination were 26.7% and 6.4%,
      respectively; and for those who experience racial discrimination as extremely vs
      mildly stressful, rates were 42.2% and 20.8%, respectively. We conclude that the
      stress of racial discrimination may play an important role in smoking among
      Blacks and, therefore, warrants further investigation.

PMID- 10892826
TI  - Chronotropic dose response of atropine in Nigerians with congestive heart
      failure: assessment of ethnic variation and reversibility of parasympathetic
      dysfunction.
AB  - Both ethnicity and disease states may influence cardiac parasympathetic tone. We
      evaluated the cardiac vagal activity in 9 Nigerians aged 57(11) with congestive
      heart failure, and 9 age- and sex-matched healthy controls aged 51(11) years,
      using a cumulative low dose atropine response curve. All subjects demonstrated
      bradycardia at low doses (100 microg-400 microg) and tachycardia at higher doses
      (600 microg-1,000 microg). However, both the bradycardic and the tachycardic
      responses were attenuated in heart failure patients compared to controls:
      bradycardia -1.1(1.5) beats/min in heart failure patients vs -7.1(2.2) beats/min
      in controls (P<.01) and tachycardia +4(1.5) beats/min in heart failure patients
      vs +14.3(3) beats/min in healthy controls (P<.01). EC50 values for brachycardia
      and tachycardia calculated from the dose response curves were significantly
      higher in healthy controls compared to heart failure patients, for bradycardia
      69(39) microg versus 11(1.6) microg (P<.01) and tachycardia 682(61) microg vs
      254(84) microg (P<.01). Treatment of heart failure for 4 weeks with furosemide,
      digoxin and angiotensin converting enzyme inhibitor (enalapril) caused a
      significant increase in the magnitude of both the bradycardic responses from 
      1.1(1.5) beats/min to -4.4(0.9) beats/min after treatment, and tachycardic
      responses from +4(1.5) beats/min to +10.(2.3) beats/min 4 weeks after treatment
      (P<.05). After 4 weeks of treatment, EC50 was also increased significantly toward
      normal values. For tachycardia, the values were 254(88) microg before treatment
      vs 529(78) microg after treatment (P<.05); and for bradycardia, the values were
      2.5(1.6) microg before treatment vs 30(13) microg after treatment (P<.05). These
      findings demonstrate the early bradycardic effect of atropine in Black Africans
      (both healthy controls and heart failure patients), contradicting earlier reports
      of its absence in the negroid race. This confirms the reduction in cardiac
      parasympathetic responsiveness (both maximal heart rate change and EC50) in
      hypertensive heart failure using a pharmacological assay. It demonstrates the
      augmentation and amelioration of cardiac vagal tone with enalapril-dixogin
      diuretic therapy in non-ischemic heart failure, and the sequential utility of the
      low dose atropine-chronotropic response in assessing cardiac parasympathetic
      activity.

PMID- 10892827
TI  - Variations in serum carotenoid concentrations among United States adults by
      ethnicity and sex.
AB  - Increased fruit and vegetable intake is associated with a lower risk of heart
      disease and cancer. Carotenoids, which occur primarily in fruits and vegetables,
      have been associated with reduced risk of some chronic diseases. To examine the
      distribution of serum carotenoid concentrations among US adults by ethnicity and
      sex, the author used data from the Third National Health and Nutrition
      Examination Survey, conducted from 1988 to 1994. After exclusions, 14,914
      participants aged > or =20 years who attended the medical examination clinic had
      their serum carotenoid concentrations determined. Mexican-American men had higher
      total concentrations than European Americans and African Americans. In general,
      European-American participants were characterized by high lycopene but low beta
      cryptoxanthin and lutein/zeaxanthin concentrations; African Americans by high
      lutein/zeaxanthin and low alpha-carotene and beta-cryptoxanthin concentrations;
      and Mexican Americans by high alpha-carotene, beta-cryptoxanthin, and
      lutein/zeaxanthin concentrations. The implications of these different carotenoid
      concentration patterns for future risk of disease within the ethnic and sex
      groups remain to be clarified.

PMID- 10892828
TI  - Patterns of prescription drug utilization in elder Mexican Americans: results
      from the Hispanic EPESE Study. Established Population for the Epidemiologic Study
      of the Elderly.
AB  - The objective of this study was to determine the patterns of prescription
      medication usage among community-dwelling Mexican-American elders. This was a
      cross-sectional survey of a regional probability sample of 2,895 community
      dwelling Mexican Americans, aged 65 and over. Of the sample, 58.1% used at least
      one prescribed medication within the two weeks prior to their participation in
      the study. Women were significantly more likely than men to use analgesics, non
      steroidal anti-inflammatory agents, prescription nutritional supplements, and
      other central nervous system and endocrine medications. Subjects aged 75 and over
      were more likely to use cardiovascular medications, nutritional supplements,
      ophthalmic preparations and antihistamines, while those in the age groups 65-69
      and 70-74 were more likely to use hypoglycemic and endocrine medications.
      Interestingly, there was a significantly decreased usage of hypoglycemic
      medications in the older age group (aged 75 and over) as compared with the
      younger age groups (65-69 and 69-74). This may indicate that Mexican American
      elders are dying at younger ages from complications related to diabetes mellitus
      and are not alive to use hypoglycemic medications at ages 75 and over. Also, men
      used more hypoglycemic medication than women (77% vs 70%). There was no
      relationship between use of medication and severity of diabetic illness.

PMID- 10892829
TI  - Arthritis in Indian country: determining the prevalence and effects.
AB  - OBJECTIVE: This project was designed to determine the prevalence of self-reported
      arthritis and its effect on the daily lives of Chippewa Indian people on tribal
      lands in Wisconsin. DESIGN AND METHODS: After review and approval by the LCO
      Tribal Council and the University of Minnesota Human Subjects Committee, face-to
      face interviews with randomly selected tribal residents were conducted, followed
      by focus group formation, and medical chart reviews. RESULTS: Eighty-one percent
      (N = 82) of the eligible sample were interviewed. Fifty-six percent (N = 46) self
      reported a diagnosis of arthritis, either by physician report or description of
      symptoms confirmed by a rheumatologist. Seventy-eight percent of this group (N =
      36) reported limitations in their activities that can be attributed to arthritis.
      Only half of the medical charts included the diagnosis of arthritis or any tests
      to document its diagnosis. CONCLUSIONS: In this Chippewa population, the
      prevalence of and limitations due to arthritis are extremely high. Reasons for
      this need further investigation. The implications of these findings for tribal
      and health planning include housing, community activities, and medical services
      to accommodate the needs of this group.

PMID- 10892830
TI  - A pilot study comparing the level of sickle cell disease knowledge in a
      university in southeastern Texas and a university in Enugu, Enugu State, Nigeria,
      West Africa.
AB  - Sickle cell disease is the most commonly inheritable blood disorder in man.
      Sickle cell anemia affects approximately one in 375 Blacks in the United States.
      There is yet no known cure for this disease. Families of sickle cell patients
      continue to be financially and emotionally devastated by sickle cell disease
      complications. A high level of sickle cell disease knowledge will encourage non
      directional sickle cell disease counseling that would reduce the incidence of
      this disease. A pilot study to determine the level of sickle cell disease
      knowledge in a university in southeastern Texas and a university in Enugu, Enugu
      State, Nigeria, West Africa found that there was a need to improve retention of
      sickle cell disease factual information.

PMID- 10892831
TI  - Coping strategies in families of children with sickle cell disease.
AB  - OBJECTIVE: To examine the impact of family environment, morbidity, and
      socioeconomic status (SES) on coping strategies in families of children with
      sickle cell disease. DESIGN: A cross-sectional study. METHODS: The study sample
      consisted of 40 mothers, 24 fathers, 40 patients, and 28 healthy siblings from 40
      African-American families, each of which had only one child with sickle cell
      disease. Data were collected through the use of structured interviews utilizing a
      demographic questionnaire, the Family Environment Scale (FES), and the COPE.
      RESULTS: The results indicate that support-seeking coping strategies were
      employed more often by mothers in more cohesive families and siblings in less
      cohesive families, while increased growth (resilience) was experienced by
      siblings in less conflicted families. Patients in more religious families
      reported greater use of religion as a means of coping. Mothers of mildly affected
      patients used acceptance more frequently than those of severely affected
      patients, and fathers of severely affected patients more often sought emotional
      support. Mothers, fathers, and siblings in low SES families reported greater use
      of denial than did those in high SES families. CONCLUSION: Additional
      psychosocial research involving families (including fathers and siblings) dealing
      with sickle cell disease is needed to facilitate the utilization of adaptive
      coping strategies, thereby enhancing individual and family adjustment.

PMID- 10892832
TI  - Factors associated with no surgery or radiation therapy for invasive cervical
      cancer in Black and White women.
AB  - This paper identifies the proportion of invasive cervical cancer cases that do
      not receive cancer-directed surgery or radiation; assesses the influence of race,
      stage, age, grade, nodal status, histology, and co-morbid cancer primaries on
      receipt of treatment; and considers reasons why cancer-directed therapy is not
      received. We analyzed data for 8,119 patients with invasive cervical cancer from
      eleven population-based tumor registries in the Surveillance, Epidemiology, and
      End Results (SEER) Program of the National Cancer Institute, 1992-96.
      Approximately 8.03% of Whites and 11.64% of Blacks did not receive surgery or
      radiation therapy (no therapy). The percentage of cases receiving no therapy were
      greatest for unstaged cases, and for cases with unknown grade or unknown lymph
      node status. Adjusted odds of no therapy significantly increased with distant and
      unstaged disease (vs local stage) and older age (vs 0-39) at diagnosis; unknown
      grade (vs well differentiated); or unknown lymph node (vs no lymph node) status.
      Black cases were more likely to be unstaged and unstaged cases are more likely to
      not receive therapy. Blacks were more likely than Whites not to receive surgery
      because it was not recommended, contraindicated due to other conditions, or
      refused. Of cases refusing radiation, 53.85% of Whites and 83.33% of Blacks
      refused surgery, and of women refusing surgery, 22.58% of Whites and 50% of
      Blacks refused radiation. Stage, age, grade, and lymph node status directly
      influence receipt of treatment. Race influences receipt of treatment indirectly
      through stage. Reasons why therapy was not received (eg, not recommended,
      refused) differ according to race and stage at diagnosis.

PMID- 10892833
TI  - Estrogen replacement therapy use in minority postmenopausal women.
AB  - OBJECTIVE: To determine the use of estrogen replacement therapy (ERT), and
      awareness of relative benefits and risks of ERT in under-served minority
      postmenopausal women. DESIGN: Survey. SETTING: General medical and geriatric
      clinics of an acute care teaching hospital in south central Los Angeles.
      PARTICIPANTS: Convenience sample of 155 postmenopausal women. MEASUREMENTS:
      Current and past ERT use, awareness of risks and benefits, reasons for not using
      ERT. RESULTS: Of the 143 African-American and Hispanic postmenopausal women, only
      16% reported current ERT use. Of the 111 women who have never taken ERT, 86%
      responded that their physicians have not discussed ERT with them. Fifteen percent
      of the women were aware of the coronary artery disease (CAD) benefit, and 22%
      were aware of the osteoporosis benefit. Eighteen percent were aware of the
      relative risk of endometrial cancer. CONCLUSION: Over 80% of the under-served
      postmenopausal women surveyed in our clinics were not receiving ERT, and most
      were unaware of the benefits and risks of ERT. Lack of physician discussion was
      cited as the primary reason. Special educational efforts to improve physician
      counseling practices for ERT in this and similar populations need to be
      developed.

PMID- 10892834
TI  - Multiple race reporting for children in a national health survey.
AB  - The 1997 standard for race and ethnicity data from the Office of Management and
      Budget requires the collection of data for multiple race groups. The aims of this
      study were to compare characteristics of multiple race children and describe race
      reporting for children within interracial and multiple race families. Descriptive
      statistics were estimated using the 1993-1995 National Health Interview Surveys.
      In this time period, 2.6% of children had more than one race reported. Multiple
      race children were a diverse group who differed from each other and their single
      race counterparts. For example, the percent of children reported as both Black
      and White who lived in a two-parent household (58.9%), was significantly less
      than the corresponding percents for other multiple race children (65.8%-79.6%),
      and between the corresponding percents for single race Black (42.7%) and single
      race White children (83.2%). The relationships between parental race and child's
      race varied. Although 3.1% of children in two-parent households lived with
      interracial parents, fewer than half of these children had more than one race
      reported. Sociodemographic variables were not associated with child's reported
      race among interracial families. These findings indicate that generalizations
      about multiple race children for research or policy purposes will be problematic.

PMID- 10892835
TI  - Cultural sensitivity in clinical practice.
AB  - The perspective presented in this article bridges systems theory, anthropologic
      theory and clinical application. The article argues that since human illness and
      healing occur in a sociocultural context, they must be addressed in that context.
      It further challenges health care practitioners to be more inclusive of their
      patients' cultures and more reflective of their own, in order to be more
      effective in interventions.

PMID- 10892836
TI  - Spare the rods, save the cones in aging and age-related maculopathy.

PMID- 10892837
TI  - Cone properties of retinal margin cells in the monkey (Macaca mulatta).
AB  - PURPOSE: To characterize a cell population in the monkey retinal margin that was
      labeled with a cone-specific antibody and to determine the presence of additional
      markers. METHODS: Retinal whole-mount preparations from infant and adult rhesus
      monkeys (Macaca mulatta) were immunolabeled by incubation overnight with the
      primary antibodies 7G6, a cone-specific antibody; SV2, a synaptic-vesicle
      antibody; and opsin antibodies that recognize either the short or long/middle
      wavelength-sensitive opsins. RESULTS: The retinal margin cells labeled by 7G6 lay
      within 1 mm of the ora serrata and differed from 7G6-labeled cones in the central
      retina. The margin cells possessed a soma, a fiber process, and a terminal
      enlargement that lay in the plane of the retina; no outer segment was
      discernible. A total of 5400 and 7252 margin cones cells were found in each of
      two monkeys. The terminal enlargement and soma of the labeled margin cells also
      showed SV2 immunoreactivity. Surprisingly, opsin immunoreactivity extended
      throughout the margin cell, which is consistent with the absence of a discernible
      outer segment. CONCLUSIONS: Cells with immunoreactive cone properties were found
      in the margin of the monkey retina. The absence of an outer segment and the
      presence of somatic opsin and SV2 are reminiscent of features observed in the
      central cones of fetal monkey retinas. These results suggest that a subpopulation
      of cones in the retinal margin might fail to mature completely and thus retain
      juvenile characteristics into adulthood.

PMID- 10892838
TI  - Expression of epidermal growth factor receptor: risk factor in uveal melanoma.
AB  - PURPOSE: To investigate the prognostic significance of the expression of
      epidermal growth factor receptor (EGFR) in uveal melanoma. EGFR is a
      transmembrane glycoprotein, and its expression has been correlated with the
      development of metastases in various malignancies. METHODS: Frozen sections from
      22 primary uveal melanomas were examined for EGFR expression by a three-step
      immunoperoxidase staining, using a mouse anti-human EGFR IgG2b monoclonal
      antibody. The results were compared with patient survival and clinical and
      histopathologic parameters. RESULTS: EGFR expression could not be determined on
      one tumor due to excessive pigmentation. Two patients died of causes unrelated to
      melanoma, and two patients were lost to follow-up. Out of 21 tumors, six tumors
      showed immunoreactivity for EGFR. Five of these six patients (83%) died due to
      metastases, compared with 2 (17%) of 12 patients with no EGFR expression (Kaplan
      Meier analysis P = 0.0004). EGFR-positive tumors tended to have a greater tumor
      prominence and a higher mitotic rate. CONCLUSIONS: The expression of EGFR was
      significantly correlated with death due to metastatic disease and therefore can
      be regarded as an important prognostic factor in human uveal melanoma.

PMID- 10892839
TI  - Induced myopia associated with increased scleral creep in chick and tree shrew
      eyes.
AB  - PURPOSE: To investigate the role of scleral creep in the axial elongation of
      chick and tree shrew eyes with induced myopia. METHODS: Form-deprivation myopia
      was induced with a diffusing occluder worn over one eye. Scleral samples from the
      posterior pole and equatorial regions of myopic, contralateral (control), and age
      matched normal chick and tree shrew eyes were loaded in vitro with a force of 5 g
      for 20 minutes while creep extension was monitored. The elastic behavior of
      sclera from myopic, control, and normal chick eyes was also compared. RESULTS: In
      both chick and tree shrew, posterior and equatorial scleral samples from myopic
      eyes had significantly (P < 0.05) greater creep extensions than equivalent
      samples from control and normal eyes (n = 10, each group). Among individual tree
      shrews the difference in creep rate between the sample from the myopic eye and
      that from the control eye correlated with vitreous chamber elongation (r = 0.746,
      P < 0.05) and development of myopia (r = 0.792, P < 0.01) in the deprived eye. No
      such association was found in the data from chicks. The elastic properties of
      chick sclera were unaffected in form-deprivation myopia. CONCLUSIONS: In chick
      and tree shrew, form-deprivation myopia is associated with increased creep rate
      of posterior and equatorial sclera. In tree shrew, the correlation between
      increased scleral creep rate and vitreous chamber elongation in myopic eyes
      supports the hypothesis that induced changes in the axial length of the mammalian
      eye are mediated by changes in the creep properties of the sclera.

PMID- 10892840
TI  - Ultrastructural changes in Bruch's membrane of apolipoprotein E-deficient mice.
AB  - PURPOSE: To examine the histologic and ultrastructural changes in Bruch's
      membrane (BM) in apolipoprotein E deficient [ApoE(-)] mice in comparison with age
      matched control animals. METHODS: Two-month-old (group 1) and 8-month-old (group
      2) normal control C57BL/6 mice and 2-month-old (group 3) and 8-month-old (group
      4) ApoE(-) mice were studied. All groups of mice were fed a standard rodent diet.
      The mice were killed, serum lipid levels were determined, and the eyes were
      ultrastructurally examined using standard techniques to measure the thickness of
      BM. The area fraction of electron-lucent (EL) particles in BM was quantified
      using point-counting stereology. RESULTS: The serum cholesterol levels of the
      ApoE(-) mice were significantly higher than those of the control mice (P =
      0.0001). There was a significant thickening and EL particle accumulation in BM
      associated with age in the control animals. Group 2 had a thicker BM and more EL
      particle accumulation than group 1 (P = 0.0410 for thickness; P = 0.0042 for
      particle accumulation). Age-related changes were not seen in ApoE(-) mice;
      thickness and accumulation were similar in groups 3 and 4 (P = 0.50, thickness; P
      approximately/= 1.0, accumulation). Significant thickening and accumulation were
      seen in young ApoE(-) mice (group 3) versus young control animals (group 1; P =
      0.008, thickening; P < 0.0001, EL particle accumulation). Group 4 ApoE(-) mice
      did not have a thicker BM or more EL particles than group 2 control animals (P =
      0.2910, thickness; P = 0.35, EL particle accumulation). "Membrane-bounded"
      material (material between two membranes) was present significantly more
      frequently in ApoE(-) mice. CONCLUSIONS: ApoE(-) mice exhibit accumulation of EL
      particles at an earlier age and have more membrane-bounded material in BM than
      control mice. This material has ultrastructural similarities to basal linear
      deposit, which accumulates in age-related maculopathy.

PMID- 10892841
TI  - Form deprivation myopia in mature common marmosets (Callithrix jacchus).
AB  - PURPOSE: Experimental manipulations of visual experience are known to affect the
      growth of the eye and the development of refractive state in a variety of species
      including human and nonhuman primates. For example, it is well established that
      visual form deprivation causes elongation of the eye and myopia. The effects of
      such manipulations have generally been examined in neonatal or juvenile animals.
      Whether adolescent common marmosets (a new world primate) are susceptible to form
      deprivation myopia was studied. METHODS: Five adolescent marmosets were used in
      this study. Monocular form deprivation was induced by lid closure for 12 to 20
      weeks, starting between 299 and 315 days of age. The effects of deprivation were
      assessed with keratometry, A-scan ultrasonography, and cycloplegic refractions.
      Both eyes (treated and fellow control) were measured before lid-closure, at the
      end of the deprivation period, and several times over the following 8 to 12
      weeks. RESULTS: Adolescent marmosets are susceptible to visual form deprivation
      myopia. The experimental eyes showed significant axial elongation and myopia
      relative to the fellow control eyes. These changes were smaller, however, than
      those observed in younger eyes deprived for comparable periods. Like juvenile
      animals, the adolescent marmosets did not show recovery from myopia over the
      period monitored. CONCLUSIONS: The period for susceptibility to form deprivation
      myopia in the marmoset monkey extends beyond the early developmental period when
      ocular growth is rapid and emmetropization normally takes place. Visual form
      deprivation in adolescent marmosets with adult-sized eyes results in increased
      ocular growth and myopia. These data suggest that visual factors may influence
      the growth and refractive development of the human eye after puberty and may be
      involved in late-onset myopia.

PMID- 10892842
TI  - Decreased proteoglycan synthesis associated with form deprivation myopia in
      mature primate eyes.
AB  - PURPOSE: The rate of proteoglycan synthesis was measured in the scleras of
      adolescent marmosets that had undergone monocular form deprivation to
      characterize the scleral extracellular matrix changes associated with the
      development of myopia in a mature primate. METHODS: Form deprivation myopia was
      induced in adolescent marmosets by unilateral lid suture for an average of 108
      days. After the lids were reopened, the axial lengths and refractions were
      measured at intervals for up to 39 weeks. At the end of the study period, sclera
      were isolated and immediately radiolabeled with 35SO4 in organ culture.
      Proteoglycan synthesis rates were determined by measurement of 35SO4
      incorporation into cetylpyridinium chloride-precipitable glycosaminoglycans after
      digestion of the scleral samples with proteinase K. Collagen content was
      determined by measurement of total hydroxyproline in scleral digests. Newly
      synthesized proteoglycans were separated on a Sepharose CL-4B molecular sieve
      column and identified by their core proteins by Western blot analyses. RESULTS:
      Lid suture resulted in myopia due to a significant increase in vitreous chamber
      depth. After Sepharose CL-4B chromatography, newly synthesized scleral
      proteoglycans isolated from normal, form-deprived, and contralateral control
      eyes, resolved into one major peak that eluted in the position of decorin, a
      small chondroitin-dermatan sulfate proteoglycan. After digestion of the major
      peak with chondroitinase ABC, an approximately 45-kDa core protein was detected
      by Western blot analyses, confirming the presence of decorin. Form deprivation
      resulted in a significant reduction in the rate of proteoglycan synthesis in the
      posterior sclera (-43.55%, P < or = 0.001). Proteoglycan synthesis was also
      significantly reduced in the posterior sclera of form-deprived eyes relative to
      total collagen content (-36.19%, P < or = 0.01) and was negatively correlated
      with the rate of vitreous chamber elongation in the deprived eye (r2 = 0.779, P <
      or = 0.05). CONCLUSIONS: Significant extracellular matrix remodeling occurs in
      the posterior sclera of the adolescent primate eye during vitreous chamber
      elongation and myopia development. The negative correlation between vitreous
      chamber elongation rates and the synthesis rates of decorin in form-deprived eyes
      suggests that proteoglycan synthesis within the posterior sclera plays a role in
      the regulation of ocular size and refraction in the adolescent marmoset.

PMID- 10892843
TI  - Isolation of a novel iris-specific and leucine-rich repeat protein (oculoglycan)
      using differential selection.
AB  - PURPOSE: To identify and characterize genes expressed in the iris. METHODS: A
      human adult iris cDNA library was constructed and subjected to a differential
      selection screen to identify genes preferentially expressed in iris or trabecular
      tissue versus those expressed in lymphoblasts. Selected cDNAs were partially
      sequenced. Novel cDNAs were chosen for further analysis. The cDNAs were localized
      within chromosomes using a radiation hybrid (RH) mapping panel. The tissue
      expression profile of each cDNA was found through computer-based searches. One
      novel cDNA was subjected to 5' rapid amplification of cDNA ends and Northern blot
      analysis. RESULTS: Of 24 differentially selected clones, 14 cDNAs had homology to
      known genes, whereas the other 10 were previously uncharacterized cDNA clones.
      IR185 was one novel iris cDNA identified. Northern blot analysis with IR185
      indicated that it is expressed in human fetal liver as a 2.7-kb transcript and in
      adult iris as a 1.6-kb transcript. Computer-based searches of public databases
      and reverse transcription-polymerase chain reaction experiments have determined
      that IR185 is also expressed in retina. RH mapping experiments have localized
      IR185 to the chromosomal interval 1q31-q32, near the loci for age-related
      degeneration (1q25-q31) and retinitis pigmentosa 12 (1q31-q32), and IR185 is in
      the region for posterior column ataxia with retinitis pigmentosa (1q31-q32). It
      has a 996-bp open reading frame encoding a putative protein with homology to the
      small leucine-rich proteoglycan (SLRP) family. The IR185 gene has been
      tentatively named oculoglycan. CONCLUSIONS: Differential selection is a technique
      that has been useful in identifying genes specific to a variety of tissues. This
      is the first time this technique has been applied to the iris. Characterizing
      genes highly or uniquely expressed in the iris can assist in clarifying our
      understanding of iris function and lead to a better understanding of the
      molecular pathogenesis of ocular disease. IR185 is a tentative candidate for one
      eye disorder genetically localized to chromosome 1q31-q32.

PMID- 10892844
TI  - UV absorption by uric acid in diurnal bird aqueous humor.
AB  - PURPOSE: To analyze the components responsible for the UV absorbance in diurnal
      bird aqueous humor. METHODS: The absorbance studies were carried out using a
      Hitachi spectrophotometer (U 2000). Uric acid was determined by high-performance
      liquid chromatography (LC-10 system; Shimadzu, Kyoto, Japan). Chicken and turkey
      eyes were examined. RESULTS: The UV absorbance in chicken aqueous was largely
      accounted for by the presence of protein, tryptophan, tyrosine, ascorbic acid,
      and uric acid. Ascorbic acid was low (23 micromol/l). Uric acid was, on the other
      hand, remarkably high (151 micromol/l) compared with that in mammals (cattle, 16
      micromol/l). Principally the same results were obtained in chicken and turkey.
      CONCLUSIONS: Uric acid is a significant UV-absorbing substance in the aqueous
      humor of diurnal birds with its peak absorbance at 292 nm. The hypothesis that
      the aqueous humor acts as a UV filter seems to be valid also for the avian eye.
      However, in these eyes uric acid fulfills the role that ascorbic acid does in
      mammals.

PMID- 10892845
TI  - Molecular cloning of the bovine MYOC and induction of its expression in
      trabecular meshwork cells.
AB  - PURPOSE: Myocilin gene (MYOC) was identified as one of the disease-causing genes
      of primary open-angle glaucoma. This study was conducted to establish a system
      for the investigation of the biological role of MYOC in vitro by using bovine
      eyes, which are easy to obtain and have been widely used to examine the aqueous
      outflow system. The cDNA sequence of the bovine MYOC was determined and its
      expression in bovine eyes was examined with a quantitative polymerase chain
      reaction (PCR) assay. METHODS: Bovine MYOC cDNA was obtained from cultured bovine
      trabecular meshwork cells, and part of its sequence was determined using a primer
      pair designed based on the known sequence of the human MYOC gene. The 3' and 5'
      ends of this sequence were determined using the method of 3' and 5' rapid
      amplification of cDNA ends. The induction of the MYOC gene in cultured bovine
      trabecular meshwork cells after exposure to dexamethasone was quantitatively
      examined with real-time quantitative PCR using a probe designed according to the
      sequence of the determined bovine MYOC gene. RESULTS: Bovine MYOC protein was
      composed of 490 amino acids, which was 81.6% identical with that of human MYOC
      protein. Most of the amino acid residues of which mutation was reported to cause
      glaucoma were conserved in the bovine MYOC protein. After 2 weeks of treatment
      with 500 nM dexamethasone, expression of bovine MYOC mRNA was amplified 14-fold
      (14.1+/-5.1-fold, mean +/- SEM) measured by real-time quantitative PCR.
      CONCLUSIONS: The cDNA sequence of the bovine MYOC gene had a high degree of
      similarity to that of the human MYOC gene. Investigation of the function of
      bovine MYOC may contribute to identifying the role of MYOC protein in the aqueous
      outflow system.

PMID- 10892846
TI  - A CRX null mutation is associated with both Leber congenital amaurosis and a
      normal ocular phenotype.
AB  - PURPOSE: To identify and characterize new cone rod homeobox (CRX) mutations
      associated with the Leber congenital amaurosis phenotype. METHODS: The human CRX
      gene was sequenced in 74 consecutive patients carrying the diagnosis of Leber
      congenital amaurosis. RESULTS: Two mutations were identified in CRX that cause
      frameshifts and predict severe truncations of the encoded protein. One of these,
      a 1-bp insertion, spares only nine N-terminal amino acids, removing the
      homeodomain, WSP motif, and conserved OTX domain at the C terminus. Of the CRX
      mutations described in the literature, this is the first that convincingly
      represents a null allele of the gene. Although the patient heterozygous for this
      null allele is affected with Leber congenital amaurosis, it was surprising that
      her father, who had normal vision, was heterozygous for the same mutation.
      CONCLUSIONS: These results strongly suggest that haploinsufficiency of CRX is not
      sufficient to cause a retinal disorder. Loss of function alleles of CRX appear to
      cause Leber congenital amaurosis through a recessive or multigenic mechanism.

PMID- 10892847
TI  - Evidence for a new locus for X-linked retinitis pigmentosa (RP23).
AB  - PURPOSE: X-linked retinitis pigmentosa (XLRP) is a degenerative disease of the
      retina characterized in the early stages of disease by night blindness as a
      result of rod photoreceptor loss, progressing to severe disease with loss of
      central vision by the third decade in affected males. XLRP displays exceptional
      genetic heterogeneity, with five reported loci on the human X-chromosome. To
      investigate the level of heterogeneity for XLRP in the patient pool in the
      current study, extensive haplotype analysis, linkage analysis, and mutation
      screening were performed. METHODS: Haplotype analysis of a family with diagnosed
      XLRP was scored with more than 34 polymorphic markers spanning the entire X
      chromosome, including regions already identified as harboring XLRP genes and
      retina-specific genes. Two-point and multipoint lod scores were calculated.
      Affected male DNA was amplified with primers specific for the retinoschisis gene
      (XLRS1), and the products were screened for nucleic acid alterations by direct
      automated sequencing. RESULTS: In this article haplotype and linkage data are
      presented identifying a new locus for XLRP on the short arm of the X-chromosome,
      distinct from previously reported gene localizations for XLRP. The phenotype is
      atypical, in that the onset of vision loss in the male members of this family is
      unusually early, and female obligate carriers have normal fundi and waveforms.
      Informative recombination events in this family define a locus for XLRP (RP23) on
      Xp22 between the markers DXS1223 and DXS7161, spanning approximately 15 cM. A
      maximum lod score of 2.1 was calculated for the locus order DXS7103-8 cM
      (RP23/DXS1224)-4 cM-DXS999. This new locus (RP23) encompasses the retinoschisis
      disease gene; therefore, XLRS1 was screened for a mutation. No sequence
      alteration was identified indicating that mutations in the coding region of the
      gene responsible for retinoschisis do not cause RP23. CONCLUSIONS: The results
      describe evidence for a new locus for XLRP (RP23), adding to the established
      genetic heterogeneity for this disease and the number of genes expressed in
      ocular tissue residing on the X-chromosome.

PMID- 10892848
TI  - Retinal fascin: functional nature, subcellular distribution, and chromosomal
      localization.
AB  - PURPOSE: To investigate the functional properties, subcellular localization, and
      chromosomal location of retinal fascin. METHODS: Recombinant retinal fascin
      protein was prepared by using a baculovirus-insect expression system. Actin
      binding and -bundling assays were performed with chick actin purified from
      skeletal muscle. Western blot analysis and immunohistochemistry were performed
      with a polyclonal antibody raised against bovine retinal fascin. A human retinal
      cDNA library was screened with an expressed sequence tag cDNA fragment.
      Chromosomal location was determined with fluorescent in situ hybridization.
      RESULTS: The actin-binding and actin-bundling activities of retinal fascin were
      demonstrated by high- and low-speed centrifugation assays. Formation of
      filamentous (F)-actin bundles by retinal fascin in vitro was also morphologically
      confirmed by fluorescence microscopy and electron microscopy. Immunohistochemical
      analysis revealed that retinal fascin protein was localized specifically in the
      outer and inner segments of the photoreceptor cells in the retina. Two splicing
      variants of human retinal fascin cDNA were also located. One clone encoded 492
      amino acids, and the other encoded 516 amino acids. The gene encoding retinal
      fascin was localized to human chromosome 17, region q24 -25. CONCLUSIONS: These
      results suggest that retinal fascin may play a role in formation of unique
      morphologic structures of the photoreceptor cells and is a candidate gene for
      retinal degenerative disorders.

PMID- 10892849
TI  - PCR assessment of HSV-1 corneal infection in animals treated with rose bengal and
      lissamine green B.
AB  - PURPOSE: In vivo, the ophthalmic dye rose bengal displays profound antiviral
      effects against herpes simplex virus (HSV)-1, thus limiting its utility in
      diagnosis of epithelial keratitis when used before viral culture is performed. In
      contrast, lissamine green B does not possess significant antiviral activity in
      vivo. To determine whether polymerase chain reaction (PCR) could successfully
      detect HSV-1 DNA in ocular samples that have been exposed to ophthalmic dyes,
      animal models were used to observe the presence of infectious HSV-1 and viral DNA
      in eyes treated with rose bengal or lissamine green B. METHODS: Animals were
      bilaterally infected with HSV-1 strain H129, and at daily intervals up to 16 days
      post infection (dpi) rose bengal or lissamine green B was instilled in the left
      eyes. The right eyes were not treated with dyes. Swabs of the dye-treated and
      untreated eyes were assayed by PCR for viral infectivity by culture and the
      presence of DNA specific for a fragment of the HSV-1 DNA polymerase gene.
      RESULTS: A statistically equivalent number of samples from lissamine green B
      treated and untreated eyes were positive by both viral culture and PCR. In
      contrast, rose bengal significantly decreased the infectious virus present in
      ocular secretions. A total of 44% and 78% of the rose bengal-treated and
      untreated eye samples, respectively, were positive by culture from 1 through 16
      dpi. PCR was more sensitive than culture for detection of HSV-1 in rose bengal
      treated eyes, in that 74% of rose bengal-treated samples were positive by PCR
      compared with 44% that were positive by culture during the 16-day period studied.
      It was also noted that both rose bengal and lissamine green B treatments slightly
      prolonged the period during which viral DNA was detectable in ocular secretions
      by PCR, possibly because the singlet oxygen produced by these photoreactive dyes
      compromised ocular cellular, humoral, and nonspecific immune factors allowing
      viral DNA to persist for slightly longer periods. CONCLUSIONS: PCR can
      successfully detect HSV-1 DNA in ocular samples that are culture negative and
      contain rose bengal or lissamine green B. Visualization of ocular epithelial
      defects with lissamine green B does not interfere with detection of infectious
      virus or HSV-1 DNA.

PMID- 10892850
TI  - Age-related decreases in the prevalence of myopia: longitudinal change or cohort
      effect?
AB  - PURPOSE: The prevalence of myopia shows a decline with age in cross-sectional
      studies. This pattern may represent an increase in the prevalence of myopia in
      younger generations, possibly through increased exposure to near work, or an
      intrinsic age-related decline in myopia prevalence. Data were analyzed from
      published studies to determine which of these two alternatives better explains
      the data: a cohort effect of changing prevalence by decade or a longitudinal
      effect of changing prevalence as a function of age. METHODS: Prevalence data were
      taken from three studies conducted in the late 1980s and compared with those
      obtained indirectly from a national survey conducted in the early 1970s. The
      prevalence of myopia was then plotted as a function of age and year of birth.
      RESULTS: The pattern of change in the prevalence of myopia as a function of age
      was consistent across all studies when data were scaled relative to the
      prevalence of myopia at age-range midpoints from 44.5 to 49.5 years. The pattern
      of change was not consistent as a function of year of birth. When the data were
      scaled relative to the prevalence of myopia among those with years of birth from
      1940 to 1942 and plotted by year of birth, results from the early 1970s were
      offset from those of later studies by approximately 18 years. CONCLUSIONS: The
      decline in the prevalence of myopia in older adults between the early 1970s and
      the late 1980s can be better explained by age than by year of birth. The
      prevalence of myopia appears to decrease because of an intrinsic age-related
      decrease in the amount of an individual's myopia rather than because of a cohort
      effect of increasing prevalence over time. The hypothesis that increasing
      environmental exposures to near work in recent decades have changed the
      prevalence of myopia is not supported by this analysis.

PMID- 10892851
TI  - Congenital and infantile cataract in the United Kingdom: underlying or associated
      factors. British Congenital Cataract Interest Group.
AB  - PURPOSE: Prevention of visual impairment and blindness in childhood due to
      congenital and infantile cataract is an important international goal. Preventive
      strategies require information about etiology that is currently unavailable for
      many regions of the world. From a national epidemiologic study, the underlying or
      associated factors in newly diagnosed cases of congenital or infantile cataract
      in the United Kingdom are reported, and the implications for future etiological
      research are discussed. METHODS: All children with congenital or infantile
      cataract newly diagnosed during 1 year in the United Kingdom were ascertained
      independently through two national active surveillance schemes comprising
      ophthalmologists and pediatricians, respectively. Detailed information about
      cases, including disease causes, was collected from reporting clinicians using
      standard questionnaires. RESULTS: Of 243 children with newly diagnosed congenital
      or infantile cataract, 160 (66%) had bilateral disease. Isolated cataract was
      more common in bilateral than unilateral cases (61% versus 47%, P = 0.05) as was
      cataract associated with a systemic disorder (25% versus 6%, P < 0.001).
      Conversely, cataract with associated ocular anomalies was more common in
      unilateral than bilateral cases (47% versus 14%, P < 0.001). No underlying or
      associated risk factors for cataract could be identified in 92% of unilateral and
      38% of bilateral cases, although putative prenatal and perinatal risk factors
      were reported in a proportion of these idiopathic cases. Hereditary disease was
      associated with 56% of bilateral but only 6% of unilateral cases. Prenatal
      infections and other systemic factors were reported in only 6% of bilateral and
      2% of unilateral cases. CONCLUSIONS: Given the high proportion of idiopathic
      congenital and infantile cataract, the scope for primary prevention in the United
      Kingdom is currently limited. There is a need for further etiological research,
      to examine the roles of environmental and genetic risk factors for idiopathic
      cataract.

PMID- 10892852
TI  - Plasma VEGF and soluble VEGF receptor FLT-1 in proliferative retinopathy:
      relationship to endothelial dysfunction and laser treatment.
AB  - PURPOSE: To study plasma levels of vascular endothelial growth factor (VEGF, an
      index of angiogenesis), its soluble receptor (sFlt-1) and von Willebrand factor
      (vWf, an index of endothelial damage or dysfunction) in patients with
      proliferative retinopathy and corresponding changes in plasma levels after pan
      retinal photocoagulation (PRP). METHODS: Eighteen patients (10 men; age, 57+/-16
      years, mean +/- SD) with proliferative retinopathy secondary to diabetes (n = 13)
      and ischemic retinal vein occlusion (n = 5) with no previous PRP therapy were
      studied. Blood samples were obtained before and at 4 months after the last PRP
      session. Baseline (prelaser) plasma levels of VEGF, sFlt-1, and vWf (all by
      ELISA) were compared with levels in 16 diabetic patients with background
      retinopathy ("hospital controls"), and 18 healthy, age- and sex-matched "healthy
      controls." RESULTS: Patients with proliferative retinopathy had significantly
      raised plasma VEGF when compared with both control groups (P = 0.001). Patients
      with proliferative retinopathy and hospital controls had significantly raised
      plasma vWf levels when compared with healthy controls (P = 0.012). There was no
      difference in sFlt-1 levels between patients and controls (P = 0.162). After PRP,
      there was a significant reduction in plasma VEGF levels at 4 months' follow-up (P
      < 0.001), but no significant changes in plasma sFlt-1 or vWf levels. Patients
      with complete resolution of neovascularization had a trend toward lower median
      VEGF levels (80 versus 150 pg/ml, P = 0.062), but vWf levels (P = 0.50) and sFlt
      1 (P = 0.479) were not statistically different. Baseline VEGF and sFlt-1 levels
      were significantly correlated (Spearman r = 0.505, P = 0.032) but after PRP at 4
      months' follow-up, this was no longer significant (r = -0.269, P = 0.28).
      CONCLUSIONS: In this pilot study, patients with proliferative retinopathy
      demonstrate elevated peripheral markers of angiogenesis and endothelial
      dysfunction, suggesting a role for these processes in the pathogenesis of this
      condition. A fall in levels of VEGF after successful laser treatment may provide
      an opportunity for monitoring disease progression or relapse via a blood sample.

PMID- 10892853
TI  - Autosomal recessive cornea plana: in vivo corneal morphology and corneal
      sensitivity.
AB  - PURPOSE: Autosomal recessive corneal plana (RCP) is a rare corneal anomaly with
      unknown pathogenesis and a high incidence in Finland. The aim was to examine
      corneal sensitivity and the morphology of different corneal layers and subbasal
      nerves in RCP patients. METHODS: Three patients with a diagnosed autosomal
      recessive cornea plana were examined. Corneal sensitivity to different modalities
      of stimulation was tested in four corneas using noncontact esthesiometry. Tissue
      morphology of three corneas was evaluated, and in two corneas thickness of
      corneal layers was measured using in vivo confocal microscopy. RESULTS: Corneas
      of RCP patients appear to have mechanosensory, polymodal, and cold-sensitive
      nerve terminals. RCP patients had normal sensation thresholds for chemical, heat,
      and cold stimulation but a high threshold for mechanical stimulation. Their
      capacity to discriminate increasing intensities of stimulus was reduced, except
      for cold stimuli. Thickness of the epithelial layer was reduced, whereas total
      corneal and stromal thicknesses were slightly reduced or close to normal values.
      In all cases Bowman's layer was absent. Subbasal nerves had abnormal branching
      patterns. The arrangement of anterior keratocytes was altered, showing clustered
      and irregularly shaped nuclei. Increased backscattering of light in confocal
      microscopy through focusing (CMTF) profiles was observed throughout the stroma.
      Epithelial and endothelial cells appeared to be regular in shape. CONCLUSIONS:
      The present study revealed qualitative and quantitative alterations in corneal
      sensitivity, cellular morphology, and the thickness of corneal layers in RCP
      patients.

PMID- 10892854
TI  - Development of conjunctival goblet cells and their neuroreceptor subtype
      expression.
AB  - PURPOSE: To investigate expression of muscarinic, cholinergic, and adrenergic
      receptors on developing conjunctival goblet cells. METHODS: Eyes were removed
      from rats 9 to 60 days old, fixed, and used for microscopy. For glycoconjugate
      expression, sections were stained with Alcian blue/periodic acid-Schiffs reagent
      (AB/PAS) and with the lectins Ulex europeus agglutinin I (UEA-I) and Helix
      pomatia agglutinin (HPA). Goblet cell bodies were identified using anti
      cytokeratin 7 (CK7). Nerve fibers were localized using anti-protein gene product
      9.5. Location of muscarinic and adrenergic receptors was investigated using anti
      muscarinic and beta-adrenergic receptors. RESULTS: At days 9 and 13, single
      apical cells in conjunctival epithelium stained with AB/PAS, UEA-I, and CK7. At
      days 17 and 60, increasing numbers of goblet cells were identified by AB/PAS, UEA
      I, HPA, and CK7. Nerve fibers were localized around stratified squamous cells and
      at the epithelial base at days 9 and 13, and around goblet cells and at the
      epithelial base at days 17 and 60. At days 9 and 13, M2- and M3-muscarinic and
      beta2-adrenergic receptors were found in stratified squamous cells, but M1
      muscarinic and beta1-adrenergic receptors were not detected. At days 17 and 60,
      M2- and M3-muscarinic receptors were found in goblet cells, whereas M1-muscarinic
      receptors were in stratified squamous cells. Beta1- and beta2-adrenergic
      receptors were found on both cell types. Beta3-adrenergic receptors were not
      detected. CONCLUSIONS: In conjunctiva, nerves, M2- and M3-muscarinic, and beta1-
      and beta2-adrenergic receptors are present on developing goblet cells and could
      regulate secretion as eyelids open.

PMID- 10892855
TI  - Effects of oleoresin capsicum pepper spray on human corneal morphology and
      sensitivity.
AB  - PURPOSE: To examine the potential harmful effects on corneal structure,
      innervation, and sensitivity of a spray containing the neurotoxin capsaicin
      (oleoresin capsicum, OC). METHODS: Ten police officers who volunteered for the
      study were exposed to OC. Clinical signs were assessed. Corneal sensitivity was
      measured using a Cochet-Bonnet or a noncontact esthesiometer that provides
      separate measurements of mechanical, chemical, and thermal sensitivity. Tear
      fluid nerve growth factor (NGF) was measured. Corneal cell layers and subbasal
      nerves were examined by in vivo confocal microscopy. The subjects were examined
      before application and 30 minutes, 1 day, 1 week, and 1 month after OC exposure.
      RESULTS: OC spray produced occasional areas of focal epithelial cell damage that
      healed within 1 day. Each eye showed conjunctival hyperemia and in two subjects,
      mild chemosis. All except one eye had unchanged best corrected visual acuity
      (BCVA). A transient decrease (day 1) of mechanical sensitivity was observed with
      the Cochet-Bonnet esthesiometer. With the gas esthesiometer, mechanical
      sensitivity remained below normal values for 7 days. Chemical sensitivity to CO2
      was high for as much as 1 day and decreased below normal 1 week later, whereas
      sensitivity to cold was unaffected. Two subjects had measurable tear NGF that
      increased after exposure. Basal epithelial cell morphology suggested temporary
      corneal epithelial swelling, whereas keratocytes, endothelial cells, and subbasal
      nerves remained unchanged. CONCLUSIONS: Although OC causes immediate changes in
      mechanical and chemical sensitivity that may persist for a week, a single
      exposure to OC appears harmless to corneal tissues. The changes are possibly
      associated with damage of corneal nerve terminals of mainly unmyelinated
      polymodal nociceptor fibers.

PMID- 10892856
TI  - Fine needle diathermy occlusion of corneal vessels.
AB  - PURPOSE: To develop a novel technique, fine needle diathermy (FND), for the
      occlusion of corneal vessels and to evaluate its safety and efficacy in a series
      of patients. METHODS: Fourteen patients were treated with FND to occlude corneal
      vessels. Patients were categorized into four groups: group 1 (n = 4), high risk
      patients with stromal vascularization before keratoplasty; group 2 (n = 2),
      patients with progressive lipid keratopathy; group 3 (n = 4), post keratoplasty
      patients with active rejection episodes associated with vessels; and group 4 (n =
      4), patients with disciform vascularized scars with recurrent inflammation. The
      success of the treatment in terms of vessel occlusion and the clinical outcome
      were monitored. RESULTS: All patients in group 1 had successful corneal
      transplantation, and the grafts remained clear without graft rejection. Patients
      in group 2 with lipid keratopathy had 100% obliteration of vessels with
      stabilization of corneal scar. All four patients in group 3 had complete
      regression of vessels with reversal of graft rejection. Patients with
      vascularized disciform scar had resolution of the inflammation without
      recurrence. Average follow-up was 10.3 months (minimum, 6 months; maximum, 24
      months). No serious complications were observed with FND. CONCLUSIONS: FND is a
      useful and inexpensive technique that can serve as an adjunct or alternative to
      laser occlusion for the treatment of established corneal vessels. It is fairly
      safe and effective, although complications such as intrastromal bleeding and
      crystalline deposits can occur and at times it may have to be repeated once or
      twice to achieve the desired result.

PMID- 10892857
TI  - Regulation of collagenase, stromelysin, and urokinase-type plasminogen activator
      in primary pterygium body fibroblasts by inflammatory cytokines.
AB  - PURPOSE: To examine the expression patterns of extracellular matrix degrading
      enzymes in cultured primary pterygium body fibroblasts activated by cytokines and
      growth factors potentially derived from ocular surface epithelial cells and
      tears. METHODS: EGF, TGF-alpha, PDGF-BB, IL-1beta, bFGF, TGF-beta1, TNF-alpha, or
      IL-6 were added at 10 ng/ml to early passaged primary pterygium body fibroblasts
      (PBF) or normal human conjunctival fibroblasts (HJF) in a serum-free medium.
      Expression of transcripts and proteins of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1,
      TIMP-2, and uPA was determined by Northern hybridization, ELISA, and Western
      blotting, respectively. Gelatin and casein zymographies were performed in their
      serum-free conditioned media with or without enzyme inhibitors to determine the
      activity of MMP-2 and -3, respectively. RESULTS: IL-1beta and TNF-alpha
      dramatically increased the mRNA and protein expression of MMP-1 and MMP-3 in
      cultured PBF when compared to normal HJF and to their nonstimulated counterparts
      cultured in a serum-free medium. EGF and TGF-alpha also upregulated MMP-3 in PBF
      when compared to HJF. The transcript levels of MMP-2 were high but stable for the
      two cell types regardless of the cytokine treatment. Both TIMP-1 and TIMP-2
      expressions were not influenced by the cell type or the cytokine treatment. MMP-9
      was not expressed in either of these two types of fibroblasts. Both IL-1beta and
      TNF-alpha induced a significant decrease in uPA expression in PBF, whereas bFGF
      induced a slight increase in both HJF and PBF. CONCLUSIONS: Chronic inflammatory
      stimulation by IL-1beta and TNF-alpha, which potentially can be derived from the
      ocular surface and tears, may be responsible for increased expression of MMPs in
      cultured PBF. These data have clinical implications on progression of pterygium
      and recurrence associated with incomplete excision of primary PBF under the
      influence of ocular surface inflammation. Suppression of intraoperative and
      postoperative inflammation may be a new strategy to prevent pterygium recurrence.

PMID- 10892858
TI  - Inhibitory effect of PGE2 on EGF-induced MAP kinase activity and rabbit corneal
      epithelial proliferation.
AB  - PURPOSE: To determine in rabbit corneal epithelial cells in culture whether
      epidermal growth factor (EGF)-induced increases in prostaglandin (PG) E2
      production inhibit both the extracellular signal-regulated kinase 2 (Erk-2), a
      mitogen-activated protein kinase (MAPK), cascade activation, and the mitogenic
      response to this growth factor. METHODS: Serum starvation for 24 to 36 hours was
      used to synchronize cultures of SV40-transformed rabbit corneal epithelial (RCE)
      cells. The effects of exogenous PGE2, inhibition of PGE2 synthesis, and
      modulation of protein kinase A (PKA) activity on EGF-induced Erk-2 activation
      were assessed by immunoprecipitation, kinase assays, and Western blot analysis.
      PGE2 synthesis was measured by using enzyme-linked immunosorbent assay. [3H]
      Thymidine incorporation was used to measure RCE cell proliferation rates.
      RESULTS: EGF (5 ng/ml) significantly increased PGE2 production in a time
      dependent manner up to 94%+/-8% after 3 hours. EGF-induced PGE2 production was
      suppressed by AACOCF3, a phospholipase A2 (cPLA2) inhibitor. EGF-induced Erk-2
      activation reached a maximal level at 15 minutes, followed by a decline toward
      the control level after 3 hours. In the presence of either PGE2 (50 microg/ml) or
      8-CPT-cAMP (100 microM), the EGF-induced Erk-2 activation was lessened. PKA was
      activated by applications of EGF or PGE2 and suppressed by AACOCF3. On the other
      hand, either inhibition of PGE2 production with AACOCF3 or H-89, a PKA inhibitor,
      enhanced EGF-induced Erk-2 activity. Raf-1 activity was stimulated by EGF to
      maximal activity at 5 minutes and returned toward its control level after 60
      minutes. As with the dependence of Erk-2 activity on PKA activity, in the
      presence of H-89, the EGF-induced Raf-1 activation was significantly enhanced.
      DNA synthesis was increased 59%+/-5% (n = 4) after EGF stimulation, indicating a
      mitogenic effect of EGF in RCE cells. Inhibition of cPLA2 activity with AACOCF3
      increased DNA synthesis in RCE cells by another 64% relative to the effect of EGF
      alone. In contrast, with either PGE2 or 8-CPT-cAMP present the mitogenic response
      to EGF was totally suppressed. CONCLUSIONS: EGF-induced increases in PGE2
      production dampened the mitogenic response to this growth factor. This
      suppression appears to be a consequence of PGE2-elicited increases in PKA
      activity, which leads to inhibition of EGF-induced activation of MAPK cascades at
      the level of Raf-1 and further affects downstream events including Erk-2. These
      results indicate that the mitogenic response to EGF in vivo in the proliferating
      basal cell layer may be dependent on the level of its PKA activity.

PMID- 10892859
TI  - The effect of hypoxia on endogenous corneal epithelial eicosanoids.
AB  - PURPOSE: Injury to the corneal epithelium increases arachidonic acid (AA)
      metabolism through the cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome
      P450 pathways. The authors used the rabbit corneal organ culture model to
      demonstrate the effect of hypoxia on the endogenous formation of 12-hydroxy
      5,8,11,14-eicosatetraenoic acid (12-HETE), 12-hydroxy-5,8,14-eicosatrienoic acid
      (12-HETrE), and prostaglandin (PG) E2 by the intact cornea in the absence of
      exogenously added cofactors or substrate. METHODS: Rabbit corneas were isolated
      and cultured for 24 hours in normoxia or hypoxia. After culture, PGE2 in media
      was quantitated by enzyme immunoassay. 12-HETE and 12-HETrE were extracted from
      culture media and corneal epithelium and quantitated by negative chemical
      ionization-gas chromatography-mass spectrometry. COX-1 and -2 protein expression
      in corneal epithelium was determined by Western blot. Acute (2 hours) COX
      activity in normoxia and hypoxia was determined as the conversion rate of [14C]AA
      to [14C]PGE2, quantitated through reverse-phase-high-performance liquid
      chromatography and radiodetection. RESULTS: In the media of cultured rabbit
      corneas, both 12-HETE and 12-HETrE were detected, with 12-HETrE levels being four
      times higher. Hypoxia did not significantly increase extracellular 12-HETE or 12
      HETrE; however, it caused more than 90% inhibition of PGE2 synthesis.
      Intracellular 12-HETE and 12-HETrE were undetectable in normal corneas but
      increased to 7.7+/-1.3 and 2.2+/-0.4 ng/mg protein, respectively, after 24 hours
      in culture. Culture in hypoxia further increased intracellular 12-HETE threefold
      but had no additional effect on 12-HETrE. CONCLUSIONS: Hypoxia creates an
      environment in which epithelial COX activity is severely suppressed, whereas
      cytochrome P450-AA and/or 12-LOX metabolizing activity is maintained or enhanced.
      Additionally, the findings suggest that 12-HETE produced by the corneal
      epithelium acts intracellularly to promote corneal edema, whereas 12-HETrE acts
      in a paracrine manner to initiate an inflammatory cascade that can elicit
      neutrophil chemotaxis and neovascularization of the cornea.

PMID- 10892860
TI  - Eye movements in Parkinson's disease: before and after pallidotomy.
AB  - PURPOSE: To evaluate the effects of unilateral, stereotactic, posteroventral
      pallidotomy on saccadic eye movements in patients with Parkinson disease (PD).
      METHODS: Eye movements of 31 patients with moderate to advanced PD were recorded
      with an infrared system 1 month before and 3 months after pallidotomy. Two kinds
      of saccade tasks were used: saccade tasks for eliciting visually guided saccades
      and saccade tasks for eliciting internally mediated saccades (memory-guided,
      predictive, and anti-saccades). Latency, accuracy, peak velocity, and other
      parameters of saccades were evaluated. RESULTS: Internally mediated saccades were
      more impaired in patients with advanced PD compared with those with moderate PD.
      Pallidotomy did not affect visually guided saccades. After pallidotomy, the peak
      saccadic velocity of internally mediated saccades decreased. CONCLUSIONS: Hence,
      although pallidotomy has led to improvements in other motor functions, none were
      observed in saccadic responses. Rather, several modest decrements, below the
      level of clinical significance and all in internally mediated saccades, were
      observed.

PMID- 10892861
TI  - Efferent and afferent innervation of primate trabecular meshwork and scleral
      spur.
AB  - PURPOSE: To determine the correlation between nerve terminals and cells or
      extracellular matrix (ECM) components in different portions of the primate
      trabecular meshwork (TM) and scleral spur (SS). METHODS: Serial sagittal and
      tangential sections through the anterior segments of 10 cynomolgus monkey eyes
      and 12 human eyes were investigated immunohistochemically with antibodies against
      the vesicular acetylcholine transporter (VACHT), vasoactive intestinal
      polypeptide (VIP), tyrosine-hydroxylase (TH), neuropeptide Y (NPY), substance P
      (SP), calcitonin gene-related peptide (CGRP), and galanin (GAL) and with a
      reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPHd) reaction.
      The distribution of the terminals was compared with that of alpha-smooth-muscle
      actin (SMA) staining in TM and SS. The relationship between terminals and
      adjacent cells or ECM components was also studied in ultrathin sections through
      the TM and SS of 11 monkey eyes cut in sagittal, tangential, and frontal planes.
      RESULTS: NADPHd-positive nerve terminals were present, especially in the outer
      portion of both human and monkey TM and in the SS. VACHT-immunoreactive (IR)
      fibers were found in human but not in monkey SS and TM. The fibers were most
      numerous in the elongated SS and posterior TM where most cells also stained for
      SMA. SP- and CGRP-IR nerve endings were also more numerous in the outer TM and SS
      than in the inner TM. Ultrastructurally, staining for SP was seen in nerve
      endings containing mitochondria and dense core vesicles and was in contact with
      the cribriform elastic network. In the posterior SS of monkey eyes were large
      terminals similar to those previously described in human eyes. CONCLUSIONS: The
      results show for the first time that in the primate TM and SS, there are
      cholinergic and nitrergic nerve terminals that could induce contraction and
      relaxation of TM and SS cells. Terminals in contact with the elastic-like network
      of the TM and containing SP-IR resemble afferent mechanoreceptor-like terminals
      in other parts of the body. These findings raise the possibility that the TM may
      have some ability to self-regulate aqueous humor outflow.

PMID- 10892862
TI  - Simulation of longitudinal threshold visual field data.
AB  - PURPOSE: To describe and evaluate a computer model that simulates longitudinal
      visual field data. METHODS: A computer model was designed using factors that
      influence thresholds of normal and glaucomatous visual fields. The simulation
      model was used to quantify the effects of fluctuation on the outcomes of
      pointwise linear regression by comparison with simulated gold standard data with
      no variability. RESULTS: Serial sets of 10 stable and 10 progressive visual
      fields with different fluctuation levels were generated by simulation and were
      analyzed using pointwise linear regression. Regression outcome measures used were
      slopes of -1 dB/year or worse and slopes of -1 dB/year or worse that were also
      statistically significant. In stable visual fields, the number of locations with
      regression slopes worse than -1 dB/year increased with fluctuation and defect
      size and was inversely related to the number of fields. The number of locations
      with statistically significant slopes remained low and appeared unaffected by
      these variables. In progressive visual fields, analysis of a small number of
      visual field test results (<8) overestimated the number of locations with
      regression slopes worse than -1 dB/year and underestimated the number of
      locations with statistically significant slopes. CONCLUSIONS: Computer simulation
      may be used to provide a gold standard outcome that permits evaluation of
      statistical tools for monitoring progressive glaucomatous visual field loss.

PMID- 10892863
TI  - False-negative responses in glaucoma perimetry: indicators of patient performance
      or test reliability?
AB  - PURPOSE: To study whether false-negative answers in computerized glaucoma
      perimetry indicate the patient's ability to perform perimetry or test result
      reliability. METHODS: A retrospective evaluation was performed of visual field
      test results obtained with a perimetry program (Humphrey 30-2 Sita Standard;
      Humphrey Instruments, San Leandro, CA) in 70 consecutive patients with unilateral
      glaucomatous field loss. Frequencies of false-negative answers were compared
      between the two eyes of each patient and related to amount of visual field damage
      in the glaucomatous eyes using linear regression analysis. RESULTS: Frequencies
      of false-negative answers were higher in eyes with field loss. The intrapatient
      intereye difference was 6.6% on average (P < 0.0001). In seven subjects with
      false-negative frequency of 5% or more in both eyes, the mean difference was
      12.7% between eyes. The differences in false-negative answers depended
      significantly on the amount of field loss in the glaucomatous eyes (P = 0.0003).
      Larger differences were seen in patients with advanced field loss in the affected
      eye. CONCLUSIONS: The increased frequencies of false-negative answers in eyes
      with field loss were strongly associated with field status. The higher false
      negative frequencies in eyes with glaucomatous field loss compared with
      unaffected eyes may be explained by the increased variability in threshold values
      typically found in such eyes. False-negative answers in patients with glaucoma
      therefore represent eye rather than patient status.

PMID- 10892864
TI  - Photopic negative response of the human ERG: losses associated with glaucomatous
      damage.
AB  - PURPOSE: To evaluate in glaucomatous eyes the photopic electroretinogram (ERG)
      negative response (PhNR), a component that follows the b-wave peak and is thought
      to be correlated with inner retinal activity. METHODS: Eleven patients with open
      angle glaucoma (OAG) and moderate field loss (Humphrey 30-2 [Humphrey
      Instruments, San Leandro, CA] mean deviation < or = -6 dB), eight with ocular
      hypertension (OHT), and eight age-matched normal subjects were tested. Optic
      discs of patients and control subjects were evaluated by confocal scanning laser
      ophthalmoscopy. ERGs were recorded to long-duration stimuli (250 msec) of
      photopic luminance (78 candelas [cd] /m2), presented in the macular region (12
      degrees x 12 degrees field size) on a steady, adapting background. Amplitudes of
      the a-wave and b-wave and the PhNR were measured. Pattern reversal ERGs to 30
      minute checkerboards were also recorded from patients and control subjects.
      RESULTS: Compared with control subjects, patients with OAG showed reduced PhNR
      (average reduction: 62%, P < 0.01), but normal a- and b-wave amplitudes. In
      patients with OHT, PhNR and a- and b-wave amplitudes did not differ from control
      values. In individual patients with OAG, PhNR amplitudes were correlated
      positively with pattern ERG amplitudes (r = 0.80; P < 0.01) and central (12
      degrees) perimetric mean deviations (r = 0.68; P < 0.05) and negatively with cup
      to-disc area ratios (r = -0.79; P < 0.01) and cup shape measures (r = -0.78; P <
      0.01). CONCLUSIONS: Similar to that found in monkeys with experimentally induced
      glaucoma, the PhNR is selectively altered in human glaucoma. The correlation
      between PhNR losses and clinical parameter abnormalities suggests that this
      component depends on inner retina integrity and may be of clinical value for
      detecting glaucomatous damage.

PMID- 10892865
TI  - Predicting binocular visual field sensitivity from monocular visual field
      results.
AB  - PURPOSE: To compare methods of predicting binocular visual field sensitivity of
      patients with glaucoma from monocular visual field data. METHODS: Monocular and
      binocular visual fields were obtained for 111 patients with varying degrees of
      glaucomatous damage in one or both eyes, using the Humphrey 30-2 full-threshold
      procedure. Four binocular sensitivity prediction models were evaluated: BEST EYE,
      predictions based on individual values for the most sensitive eye, defined by
      mean deviation (MD); AVERAGE EYE, predictions based on the average sensitivity
      between eyes at each visual field location; BEST LOCATION, predictions based on
      the highest sensitivity between eyes at each visual field location; and BINOCUIAR
      SUMMATION, predictions based on binocular summation of sensitivity between eyes
      at each location. Differences between actual and predicted binocular
      sensitivities were calculated for each model. RESULTS: The average difference
      between predicted and actual binocular sensitivities was close to zero for the
      BINOCULAR SUMMATION and BEST LOCATION models, with 95% of all predictions being
      within +/-3 dB of actual binocular sensitivities. The best eye (MD) prediction
      had an average error of 1.5 dB (95% confidence limits [CL], +/-3.7 dB). The
      average eye prediction was the poorest, with an average error of 3.7 dB (95% CL,
      +/-4.6 dB). CONCLUSIONS: The BINOCULAR SUMMATION and BEST LOCATION models
      provided better predictions of binocular visual field sensitivity than the other
      two models, with a statistically significant difference in performance. The small
      difference in performance between the BINOCULAR SUMMATION and BEST LOCATION
      models was not statistically significant. For evaluations of functional visual
      field influences on task performance, daily activities, and related quality-of
      life issues, either the BINOCULAR SUMMATION or BEST LOCATION model provides good
      estimates of binocular visual field sensitivity.

PMID- 10892866
TI  - Regulation of connexin phosphorylation and cell-cell coupling in trabecular
      meshwork cells.
AB  - PURPOSE: To investigate the expression of functional gap junctions and the effect
      of protein kinase C (PKC) on such junctions in confluent cultures of bovine
      trabecular meshwork (TM) cells. METHODS: Expression of the gap junction protein
      connexin43 in TM cells was examined by immunofluorescence microscopy.
      Intercellular communication by gap junctions was assessed by observing the
      diffusion of fluorescent dye from an individual cell injected with lucifer
      yellow. The phosphorylation of connexin43 was evaluated by immunoblot analysis
      with a monoclonal antibody to this protein. RESULTS: Immunofluorescence staining
      revealed that connexin43 was localized to sites of contact between adjacent TM
      cells. Exposure of cells to the PKC activator phorbol 12-myristate 13-acetate
      (PMA; 10 nM, 1 hour) had no marked effect on the pattern of connexin43
      immunofluorescence. Injection of a TM cell with lucifer yellow resulted in the
      spread of the dye into neighboring cells. Dye coupling was inhibited by PMA in a
      dose- and time-dependent manner, and this inhibition was prevented by
      pretreatment of cells with the PKC inhibitor bisindolylmaleimide I. Immunoblot
      analysis of control TM cell lysates yielded connexin43 bands corresponding to the
      nonphosphorylated protein (43 kDa) and three phosphorylated forms (47, 48, and 49
      kDa). Cells exposed to PMA (10 nM, 1 hour) yielded an additional band
      corresponding to a 44-kDa form of phosphorylated connexin43 and showed a decrease
      in the intensity of the band corresponding to the nonphosphorylated protein and
      an increase in the intensity of the 47-kDa band. CONCLUSIONS: TM cells
      communicate with each other through gap junctions, and the communication is
      inhibited by PKC, probably, at least in part, through phosphorylation of
      connexin43.

PMID- 10892867
TI  - Induction of tissue transglutaminase in the trabecular meshwork by TGF-beta1 and
      TGF-beta2.
AB  - PURPOSE: To study whether human trabecular meshwork (HTM) cells are capable of
      expressing and secreting tissue transglutaminase (tTgase), an enzyme cross
      linking extracellular matrix (ECM) proteins, and whether tTgase and synthesis of
      cross-linked fibronectin are increased after treatment of HTM cells with
      transforming growth factor (TGF)-beta1 or -beta2. METHODS: Anterior segments of
      six normal human eyes were stained with antibodies to tTgase. Tissues from three
      eyes were analyzed for tTgase using Western blot analysis. Monolayer cultures of
      HTM cells from eyes of five human donors were treated with 1.0 ng/ml TGF-beta1, 
      beta2, or 5 X 10(-7) M dexamethasone (DEX) for 12 to 96 hours. Induction of
      tTgase was investigated by Western and Northern blot analysis. External tTgase
      activity was measured by the ability to form polymerized fibronectin and the
      incorporation of biotinylated cadaverine into fibronectin. RESULTS: Labeling for
      tTgase was observed throughout the entire HTM. Cultured HTM cells expressed
      tTgase intra- and extracellularly. Treatment of cultured HTM cells with TGF-beta1
      and -beta2 increased the tTgase mRNA and protein levels, whereas DEX had no
      effect. TGF-beta-treated HTM cells showed a significant increase in polymerized
      and unpolymerized fibronectin. Incorporation of biotinylated cadaverine was
      markedly increased when HTM cells were treated with TGF-beta for 24 hours before
      seeding. CONCLUSIONS: The enzyme tTgase is expressed in the HTM and is inducible
      by TGF-beta1 or -beta2 in cultured HTM cells. Extracellular tTgase is able to
      polymerize fibronectin. Increased levels of TGF-beta2 in the aqueous humor may
      lead to an increase of tTgase expression and activity in the HTM, causing an
      increase of irreversibly cross-linked ECM proteins. This mechanism might play a
      role for the increased outflow resistance seen in glaucomatous eyes.

PMID- 10892868
TI  - Effect of macrophage depletion on immune effector mechanisms during corneal
      allograft rejection in rats.
AB  - PURPOSE: In rats, corneal allograft rejection is delayed for at least 100 days by
      clodronate liposomes. These liposomes selectively deplete macrophages. To
      investigate the immunologic basis for absence of graft rejection in treated rats,
      the effect of these liposomes on the generation of cytotoxic T lymphocytes (CTLs)
      and antibody production after orthotopic corneal allotransplantation was
      determined. METHODS: Transplantations of corneal buttons from PVG rats were
      performed in AO rats. After surgery, one group received clodronate liposomes
      subconjunctivally at five time points, and the other group remained untreated. On
      postoperative day (POD) 3, 7, 12, or 17, rats were killed, the presence of CTLs
      was investigated at three different anatomic locations, and antibodies against
      donor antigens were tested. RESULTS: No significant differences were found
      between the groups tested 3 and 7 days after surgery. But on POD 12 (the time of
      onset of rejection in the untreated group) and on POD 17, the CTL activities
      detected in the submandibular lymph nodes (P < or = 0.008) and the spleen (P < or
      = 0.009) were significantly less in the treated groups compared with the
      untreated groups. In the untreated groups complement-independent antibodies were
      present only on POD 17, whereas no antibodies were found in the treated rats.
      CONCLUSIONS: Local treatment with clodronate liposomes was shown to downregulate
      local and systemic CTL responses and to prevent the generation of antibodies.
      Local depletion of macrophages in the initiation phase of the immune response
      appears to lead to a less vigorous attack on the grafted tissue and therefore to
      promote graft survival.

PMID- 10892869
TI  - Murine cytomegalovirus infection causes apoptosis of uninfected retinal cells.
AB  - PURPOSE: To determine the role of apoptosis in prevention and/or exacerbation of
      retinal disease in a mouse model of cytomegalovirus retinitis. METHODS:
      Immunocompetent or T-cell- depleted BALB/c mice were injected with murine
      cytomegalovirus (MCMV) by supraciliary injection. On sequential days after
      infection, mice were killed, and eyes were harvested for cryosectioning or for
      DNA extraction. Ocular sections were stained with monoclonal antibodies specific
      for MCMV or for T cells or used in the TdT-dUTP terminal nick-end labeling
      (TUNEL) assay to detect apoptotic cells. RESULTS: In immunocompetent BALB/c mice,
      TUNEL assays revealed that a large area of the retina was apoptotic in relation
      to the relatively small number of MCMV-infected cells that were observed in the
      subjacent choroid and/or retinal pigment epithelium. In infected eyes from T-cell
      depleted mice, there were more TUNEL-positive cells, and the areas of apoptosis
      were more extensive than in immunocompetent mice. These observations correlated
      with the increased extent of MCMV infection that is observed in the eyes of T
      cell- depleted mice. However, irrespective of immune status, TUNEL-positive
      apoptotic cells were present mainly in areas of the retina overlying areas of
      MCMV-infected choroid and/or retinal pigment epithelium. More intense DNA
      laddering, indicative of increased apoptosis, was observed in the posterior
      segments of the eyes of T-cell- depleted mice after supraciliary inoculation with
      murine cytomegalovirus compared with less intense DNA laddering in the posterior
      segments of eyes of immunocompetent MCMV-infected mice. CONCLUSIONS: The ability
      of the mouse's immune system to control MCMV infections in some tissues depends
      on induction of apoptosis in virus-infected cells. However, in the retina, cells
      undergoing apoptosis were not virus-infected, a finding that suggests that
      apoptosis of uninfected retinal cells may play a role in the pathogenesis of MCMV
      retinitis.

PMID- 10892870
TI  - A human lens model of cortical cataract: Ca2+-induced protein loss, vimentin
      cleavage and opacification.
AB  - PURPOSE: Cortical cataract in humans is associated with Ca2+ overload and protein
      loss, and although animal models of cataract have implicated Ca2+-activated
      proteases in this process, it remains to be determined whether the human lens
      responds in this manner to conditions of Ca2+ overload. The purpose of these
      experiments was to investigate Ca2+-induced opacification and proteolysis in the
      organ-cultured human lens. METHODS: Donor human lenses were cultured in Eagle's
      minimum essential medium (EMEM) for up to 14 days. The Ca2+ ionophore ionomycin
      was used to induce a Ca2+ overload. Lenses were loaded with [3H]-amino acids for
      48 hours. After a 24-hour control efflux period, lenses were cultured in control
      EMEM (Ca2+ 1.8 mM), EMEM + 5 microM ionomycin, or EMEM + 5 microM ionomycin + 5
      mM EGTA (Ca2+ < 1 microM). Efflux of proteins and transparency were monitored
      daily. Protein distribution and cytoskeletal proteolysis were analyzed at the end
      of the experiment. Cytoskeletal proteins were isolated and separated by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Western blot
      analyses were probed with anti-vimentin antibody (clone V9) and detected by
      enhanced chemiluminescence. RESULTS: Lenses cultured under control conditions
      remained transparent for 14 days in EMEM with no added supplements or serum. The
      lenses synthesized proteins and had a low rate of protein efflux throughout the
      experimental period. Ionomycin treatment resulted in cortical opacification,
      which was inhibited when external Ca2+ was chelated with EGTA. Exposure to
      ionomycin also led to an efflux of [3H]-labeled protein, amounting to 41% of the
      labeled protein over the 7-day experimental period, compared with 12% in
      ionomycin + EGTA-treated lenses. Efflux was accounted for by loss from the lens
      soluble protein (crystallin) fraction. Western blot analysis of the cytoskeletal
      protein vimentin (56 kDa) revealed a distinct breakdown product of 48 kDa in
      ionomycin-treated lenses that was not present when Ca2+ was chelated with EGTA.
      In addition, high-molecular-weight proteins (approximately 115 kDa and 235 kDa)
      that cross-reacted with the vimentin antibody were observed in ionomycin-treated
      lenses. The Ca2+-induced changes were not age dependent. CONCLUSIONS: Human
      lenses can be successfully maintained in vitro, remaining transparent for
      extended periods. Increased intracellular Ca2+ induces cortical opacification in
      the human lens. Ca2+-dependent cleavage and cross-linking of vimentin supports
      possible roles for calpain and transglutaminase in the opacification process.
      This human lens calcium-induced opacification (HLCO) model enables investigation
      of the molecular mechanisms of opacification, and the data help to explain the
      loss of protein observed in human cortical cataractous lenses in vivo.

PMID- 10892871
TI  - Polymorphic glutathione S-transferases as genetic risk factors for senile
      cortical cataract in Estonians.
AB  - PURPOSE: To investigate the possible association between glutathione S
      transferase GSTM1, GSTM3, GSTT1, and GSTP1 polymorphism and the occurrence of age
      related cataracts in Estonian patients. METHODS: Patients with cortical (155),
      nuclear (77), posterior subcapsular (120), mixed type (151) of senile cataract
      and control individuals (202) were phenotyped for GSTM1 and GSTT1 by enzyme
      linked immunosorbent assay and genotyped for GSTM3 and GSTP1 by polymerase chain
      reaction. RESULTS: The frequency of the GSTM1-positive phenotype was
      significantly higher in the cortical cataract group (60.6%) than in the controls
      (45.0%) with odds ratio of 1.88 (95% CI, 1.23-2.94; P = 0.004). The cortical
      cataract risk associated with the GSTM1-positive phenotype was increased in
      carriers of the combined GSTM1-positive/GSTT1-positive phenotype (OR = 1.99; 95%
      CI, 1.30-3.11; P = 0.002) and the GSTM1-positive/GSTM3 AA genotype (OR = 2.28;
      95% CI, 1.51-3.73; P < 0.001). The highest risk of cortical cataract was observed
      in patients having all three susceptible genotypes (OR = 2.56; 95% CI, 1.59-4.11;
      P < 0.001). Also, a significant interaction between the presence of the GSTP1* A
      allele and cortical cataract was found with prevalence of the GSTP1* A allele
      among the cortical cataract cases compared with the controls. Ninety-five percent
      of subjects with cortical cataract had the GSTP1 (AA, AB, or AC) genotype,
      whereas in controls 87% of persons had a genotype with GSTP1*A allele (OR = 3.1;
      95% CI, 1.31-7.35; P = 0.007). In contrast to the GSTP1*A allele, the presence of
      the GSTP1*B allele in one or two copies leads to decreased cortical cataract risk
      (OR = 0.09 for GSTP1 BB genotype). CONCLUSIONS. The GSTM1-positive phenotype as
      well as the presence of the GSTP1*A allele may be a genetic risk factor for
      development of cortical cataract.

PMID- 10892872
TI  - Effect of brimonidine on rabbit trabecular meshwork hyaluronidase activity.
AB  - PURPOSE: To study the presence of hyaluronidase activity in the rabbit trabecular
      meshwork and its regulation by brimonidine. METHODS: A spectrophotometric assay
      that consists of the assessment of N-acetylhexosamine groups released from
      hyaluronic acid was used to examine hyaluronidase activity. Cyclic adenosine
      monophosphate (cAMP) levels were assessed by radioimmunoassay. RESULTS:
      Hyaluronidase activity was detected in the rabbit trabecular meshwork. Its
      optimal activity was in the acid range of pH 3.8. Brimonidine significantly
      increased trabecular hyaluronidase-specific activity and decreased cAMP
      accumulation. Yohimbine significantly inhibited the effect of brimonidine on both
      hyaluronidase activity and cAMP accumulation. CONCLUSIONS: The finding of
      endogenous hyaluronidase activity in rabbit trabecular meshwork supports the
      hypothesis that this tissue can metabolize its own glycosaminoglycan (GAG)
      products. The present results suggest, however, that the hypotensive effect of
      brimonidine could be mediated, at least in part, by its ability to increase GAG
      catabolism, probably through a cAMP-independent mechanism.

PMID- 10892873
TI  - Protective effect of bradykinin against glutamate neurotoxicity in cultured rat
      retinal neurons.
AB  - PURPOSE: To identify the localization and expression of bradykinin (BK)-B2
      receptors in rat retina and examine the effects of BK on glutamate-induced
      neurotoxicity using cultured rat retinal neurons. METHODS: An immunohistochemical
      study using a specific antibody against BK-B2 receptor was performed with rat
      retina. Primary cultures were obtained from the retina of fetal rats (gestation
      day 17-19). Expression of BK-B2 receptor mRNA was determined by reverse
      transcription-polymerase chain reaction (RT-PCR) using total RNA obtained from
      cultured retinal neurons. Cultured cells were exposed to glutamate (1 mM) for 10
      minutes and followed by incubation in glutamate-free medium for 1 hour. The
      effects of BK were assessed by simultaneous application of BK with glutamate. The
      neurotoxic effects on retinal cultures were quantitatively assessed by the trypan
      blue exclusion method. RESULTS: Immunohistochemical study demonstrated that BK-B2
      receptors were expressed in the ganglion cell, inner nuclear layers, and outer
      nuclear layers. Furthermore, BK-B2 receptor mRNA expression was observed in
      cultured retinal neurons. Cell viability was markedly reduced by 10-minute
      exposure to 1 mM glutamate followed by a 1-hour incubation in glutamate-free
      medium. Simultaneous application of BK at concentrations of 0.001 to 1 microM
      with glutamate demonstrated dose-dependent protection against glutamate
      neurotoxicity. The protective action of BK (1 microM) was inhibited by
      simultaneous application of BK-B2 receptor antagonist, Hoe140 (1 microM).
      Furthermore, 1 microM BK had protective effects on neurotoxicity induced by 1
      microM ionomycin, a calcium ionophore, and sodium nitroprusside (SNP, 500
      microM), a nitric oxide (NO)-generating agent. However, BK did not inhibit
      neurotoxicity induced by 3-morpholinosydnonimine (SIN-1, 10 microM), an NO and
      oxygen radical donor. CONCLUSIONS: These results suggest that BK-B2 receptors
      were distributed in rat retinas and cultured retinal neurons and that BK had a
      protective action against glutamate neurotoxicity through BK-B2 receptors in
      cultured retinal neurons. It is suggested that BK-induced protection against
      glutamate neurotoxicity took place downstream to NO generation and upstream to
      oxygen radical generation.

PMID- 10892874
TI  - Transient Ca2+-activated Cl-currents with endothelin in isolated arteriolar
      smooth muscle cells of the choroid.
AB  - PURPOSE: To characterize the effects of endothelin (ET)-1 on the Ca2+-activated
      Cl- conductance of choroidal arteriolar smooth muscle. METHODS: Microvascular
      smooth muscle cells were enzymatically isolated from choroidal arterioles from
      the eyes of freshly killed rabbits. Cells were voltage-clamped at -60 mV using
      the whole-cell perforated patch-clamp technique. Internal pipette solutions were
      K+ based and contained amphotericin B (200 microg/ml). The cells were bathed in a
      20 mM tetraethyl-ammonium solution to block outward K+ currents. RESULTS: Within
      2 to 5 seconds of adding ET-1 (10 nM), inward current pulses were generated at a
      frequency of around 1 Hz. These evoked transient inward currents were blocked by
      niflumic acid (10 microM) or anthracene-9-carboxylic acid (1 mM). They were
      increased 2.4+/-0.1-fold when Cl- was replaced by I in the bathing medium and
      lost within 4 minutes when external Cl- was reduced from 151.6 to 20 mM. The
      reversal potential was -1+/-2 mV with 135 mM Cl- in the recording pipette and
      with 54 mM Cl it was -18+/-4 mV. When gramicidin D (100 microg/ml), which
      maintains [Cl-]i, was used instead of amphotericin B, the reversal potential was 
      18+/-1 mV. Ca2+ release by caffeine (10 mM) produced a single transient inward
      current. Endothelin-evoked transient inward currents were slowly reduced and
      eventually abolished in Ca2+-free solution (approximately 2 to 3 minutes) and
      were eliminated after approximately 30 seconds by the sarcoplasmic reticulum Ca2+
      uptake inhibitor cyclopiazonic acid (5 microM). The ET(A) receptor antagonist
      BQ123 (1 microM) prevented an effect by endothelin but did not inhibit the
      current oscillations once they had been triggered. CONCLUSIONS: In choroidal
      arteriolar smooth muscle ET-1 evokes transient inward Ca2+-activated Cl- currents
      induced through the cyclical release and re-uptake of Ca2+ from intracellular
      stores after ET(A) receptor stimulation.

PMID- 10892875
TI  - Computer-assisted quantitation of choroidal neovascularization for clinical
      trials.
AB  - PURPOSE: To develop a computer-assisted method for the quantitation of choroidal
      neovascularization (CNV) for the support of clinical trials. METHODS: Fluorescein
      angiographic images were selected from 5 patients enrolled in a clinical trial
      for which three follow-up visits were available. Thirty- and 600-second images
      were digitized at 1000 dots/in and registered (aligned) with polynomial warping
      algorithms. Custom-developed software allowed for coarse, automated
      identification of CNV. An easy-to-use graphical user interface facilitated
      supervision and refinement of the lesion boundaries by a skilled reader based on
      standard stereoscopic viewing of the fluorescein angiography study. Capabilities
      for boundary delineation in both early and late phases, and animation to allow
      for image correlation and evaluation of temporal changes in fluorescence of
      spatially corresponding pixels, were included. Two metrics for CNV
      characterization were generated. First, the lesion area based on the lesion
      boundaries was identified after supervision. Second, an integrated lesion
      intensity (ILI) reflecting the integrated, normalized lesion hyperfluorescence
      was calculated. RESULTS: Area and ILI measures were calculated for each of 5
      patients for three or more visits. Facile supervision based on the stereoscopic
      angiogram permitted arbitrarily close concordance with CNV identification using
      standard methods. Changes in area and ILI measurements between visits correlated
      closely with clinically observed changes in each case. CONCLUSIONS: Interactive
      image processing permits efficient, accurate, computer-assisted CNV quantitation
      that may be useful for the support of clinical trials and preclinical studies.

PMID- 10892876
TI  - Plasminogen activator inhibitor (PAI)-1 overexpression in retinal microvessels of
      PAI-1 transgenic mice.
AB  - PURPOSE: Previous studies have suggested that disturbances in plasminogen
      activator inhibitor (PAI)-1 may be relevant to the development of diabetic
      microvascular complications. To determine whether overexpression of PAI-1 in
      cells of retinal microvasculature would result in a disease similar to that
      observed in diabetes, ocular tissue from transgenic mice that overexpress human
      PAI-1 were examined. METHODS: Transgenic mice were administered ZnSO4 (25 mM) in
      their water for up to 49 weeks to activate the metallothionein promoter and
      stimulate human PAI-1. Colloidal gold immunocytochemistry was used to quantify
      the human PAI-1 antigen at 7, 20, 34, and 49 weeks of ZnSO4 administration. Cross
      sections of retinal microvessels were examined by electron microscopy for changes
      in basement membrane (BM) thickness. Retinal digest preparations were examined by
      light microscopy for possible microangiopathy, including changes in endothelial
      cell-to-pericyte ratios. RESULTS: Human PAI-1 immunoreactivity was detected
      throughout the retinal capillaries of transgenic mice receiving zinc and
      increased significantly (P < 0.001) after 20 to 49 weeks of ZnSO4 administration
      compared with age-matched transgenic control mice. At 20 and 49 weeks, retinal
      capillaries of transgenic mice that received zinc showed significantly thickened
      BMs compared with control animals (P < 0.001). Moreover, wholemounts of the
      retinal vasculature from PAI-1 transgenic mice demonstrated an increased
      endothelial cell-to-pericyte ratio. CONCLUSIONS: PAI-1 overexpression in retinal
      microvasculature leads to retinal disease similar to that observed in diabetic
      retinopathy.

PMID- 10892877
TI  - Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin.
AB  - PURPOSE: A fluorescent component of lipofuscin, A2-E (N-retinylidene-N
      retinylethanol-amine) has been shown to impair lysosomal function and to increase
      the intralysosomal pH of human retinal pigment epithelial (RPE) cells. In
      addition to its lysosomotropic properties A2-E is known to be photoreactive. The
      purpose of this study was to determine the phototoxic potential of A2-E on RPE
      cells. METHODS: A2-E (synthesized by coupling all-trans-retinaldehyde to
      ethanolamine) was complexed to low-density lipoprotein (LDL) to allow for
      specific loading of the lysosomal compartment. Human RPE cell cultures were
      loaded with the A2-E-LDL complex four times within 2 weeks. A2-E accumulation was
      confirmed by fluorescence microscopy and flow cytometry analysis. Acridine orange
      staining allowed assessment of lysosomal integrity and intralysosomal pH. The
      phototoxic properties of A2-E were determined by exposing A2-E-free and A2-E-fed
      RPE cell cultures to short wavelength visible light (400-500 nm) and assessing
      cell viability and lysosomal integrity. RESULTS: Fluorescence microscopy and flow
      cytometry analysis demonstrated that the intralysosomal accumulation of A2-E in
      cultured RPE cells increased with the number of feedings. Acridine orange
      staining confirmed that the A2-E was located in the lysosomal compartment and
      induced an elevation of intralysosomal pH. Exposure of A2-E-fed cells to light
      resulted in a significant loss of cell viability by 72 hours, which was not
      observed in either RPE cells maintained in the dark or A2-E-free cultures exposed
      to light. Toxicity was associated with a loss of lysosomal integrity.
      CONCLUSIONS: A2-E is detrimental to RPE cell function by a variety of mechanisms:
      inhibition of lysosomal degradative capacity, loss of membrane integrity, and
      phototoxicity. Such mechanisms could contribute to retinal aging as well as
      retinal diseases associated with excessive lipofuscin accumulation-for example,
      age-related macular degeneration and Stargardt's disease.

PMID- 10892878
TI  - Peroxisome proliferator-activated receptor-gamma ligands inhibit choroidal
      neovascularization.
AB  - PURPOSE: To determine the antiangiogenic effects of peroxisome proliferator
      activated receptor (PPAR)-gamma agonists on ocular cells involved in the
      pathogenesis of choroidal neovascularization (CNV) in vitro and on experimental
      laser photocoagulation-induced CNV in vivo. METHODS: PPAR-gamma expression in
      human retinal pigment epithelial (RPE) cells and bovine choroidal endothelial
      cells (CECs) was determined using an RNase protection assay and Western blot
      analysis. Two PPAR-gamma ligands, troglitazone (TRO) and rosiglitazone (RSG; 0.1
      20 microM), were used to assess effects on RPE and CEC proliferation and
      migration and CEC tube formation in response to vascular endothelial growth
      factor (VEGF). The effects of intravitreal injection of TRO on laser
      photocoagulation-induced CNV lesions in rat eyes (15 experimental, 15 control,
      nine burns per eye) and cynomolgus monkey eyes (two experimental, two control,
      seven paramacular burns per eye) was assessed by fluorescein angiography and
      histologic evaluation. RESULTS. PPAR-gamma1 was expressed in both RPE and CEC.
      PPAR-gamma ligands significantly inhibited VEGF-induced migration and
      proliferation in both cell types and tube formation of CEC in a dose-response
      manner. CNV in rats was markedly inhibited by intravitreous injection of TRO (P <
      0.001). Lesions showed significantly less fluorescein leakage and were
      histologically thinner in the TRO-treated animals. Similar findings were present
      in the TRO-treated lesions in two monkey eyes. The drug showed no apparent
      adverse effects in the adjacent retina or in control eyes. CONCLUSIONS: The
      inhibition of VEGF-induced choroidal angiogenesis in vitro, and CNV in vivo by
      PPAR-gamma ligands suggests the potential application of these agents in the
      large group of patients with age-related macular degeneration complicated by CNV.

PMID- 10892879
TI  - Photoreceptor degeneration in the RCS rat attenuates dendritic transport and
      axonal regeneration of ganglion cells.
AB  - PURPOSE: Photoreceptor loss in the Royal College of Surgeons (RCS) rat deprives
      the retinal ganglion cells (RGCs) of sensory input, which could interfere with
      RGC physiology. Whether axonal and dendritic transport is altered, and whether
      RGCs retain their capacity to regenerate their axons, both in vivo and in
      culture, was ascertained. METHODS: The study was conducted at postnatal days (P)
      30 (while most photoreceptors are still intact), P90 (photoreceptors being almost
      completely absent), and P180 (approximately 3 months after photoreceptor
      disappearance). RGCs were studied with retrograde transport of the fluorescent
      dye 4Di-10ASP. Dendritic transport was also studied with 4Di-10ASP that is
      transported from the cell bodies into the RGC dendrites. Regeneration of RGC
      axons in vivo was monitored in the grafting paradigm of replacing the cut optic
      nerve (ON) with a sciatic nerve (SN) piece. Cell counts were performed in retinal
      wholemounts. Axonal regrowth in vitro was assessed in organotypic cultures of
      retinal stripes. RESULTS: Photoreceptor dystrophy did not adversely affect
      retrograde axonal transport but attenuated dendritic transport compared with the
      wild-type control rats. Axons of RGCs were able to regenerate if provided with a
      SN graft, and regeneration was observed to be similar between RCS and wild-type
      rats at P30 but differed significantly at P90 and P180. In addition to an age
      dependent decline in the regenerative ability, seen also in control animals, the
      number of RCS RGCs able to regenerate declined drastically beginning at 3 months.
      It is plausible that the intraretinal reorganization, as a consequence of
      photoreceptor disappearance, interferes with the regenerative ability of the
      RGCs. CONCLUSIONS: The findings suggest for the first time that diminution of
      photoreceptor sensory input does not induce detectable death of RGCs until P180,
      but that it attenuates certain ganglion cell functions like intraretinal
      dendritic transport and propensity for axonal regeneration.

PMID- 10892880
TI  - Somatostatin receptor 2A expression in choroidal neovascularization secondary to
      age-related macular degeneration.
AB  - PURPOSE: The growth of ocular neovascularization is regulated by a balance
      between stimulating and inhibiting growth factors. Somatostatin affects
      angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and
      also has a direct antiproliferative effect on human retinal endothelial cells.
      The purpose of our study is to investigate the expression of somatostatin
      receptor (sst) subtypes and particularly sst subtype 2A (sst2A) in normal human
      macula, and to study sst2A in different stages of age-related maculopathy (ARM),
      because of the potential anti-angiogenic effect of somatostatin analogues.
      METHODS: Sixteen eyes (10 enucleated eyes, 4 donor eyes, and 2 surgically removed
      choroidal neovascular [CNV] membranes) of 15 patients with eyes at different
      stages of ARM were used for immunohistochemistry. Formaldehyde-fixed paraffin
      embedded slides were incubated with a polyclonal anti-human sst2A antibody. mRNA
      expression of five ssts and somatostatin was determined in the posterior pole of
      three normal human eyes by reverse transcriptase-polymerase chain reaction.
      RESULTS: The immunohistochemical expression of sstA in newly formed endothelial
      cells and fibroblast-like cells was strong in fibrovascular CNV membranes. mRNA
      of sst subtypes 1, 2A, and 3, as well as somatostatin, was present in the normal
      posterior pole; sst subtypes 4 and 5 were not detectable. CONCLUSIONS: Most early
      formed CNV in ARM express sst2A. The presence of mRNA of sst subtype 2A was
      observed in normal human macula, and subtypes 1 and 3 and somatostatin are also
      present. sst2A receptors bind potential anti-angiogenic somatostatin analogues
      such as octreotide. Therefore, somatostatin analogues may be an effective therapy
      in early stages of CNV in ARM.

PMID- 10892881
TI  - TGF-beta1, TGF-beta receptor II and ED-A fibronectin expression in myofibroblast
      of vitreoretinopathy.
AB  - PURPOSE: Formation of scarlike epiretinal membranes (ERMs) constitutes
      potentially the end stage of evolution of proliferative vitreoretinopathy (PVR)
      and proliferative diabetic retinopathy (PDR). Among various cellular populations,
      ERMs contain cells with contractile features typical of myofibroblasts. The
      current study was conducted to investigate the presence of transforming growth
      factor (TGF)-beta1, TGF-beta receptor II (RII) and ED-A fibronectin (FN), the
      main inducers of myofibroblastic differentiation in ERMs in PDR and PVR. METHODS:
      Samples of ERM were obtained from 23 patients during microsurgery for PVR or PDR.
      Electron microscopy, immunohistochemistry, and confocal microscopy with
      antibodies recognizing beta-smooth muscle (SM) actin, desmin, TGF-beta1, TGF-beta
      receptors I and II, and ED-A FN were performed. RESULTS: alpha-SM actin was
      detected in all ERMs, whereas desmin was present in 50% of the cases. ED-A FN was
      expressed in all ERMs in close relation with alpha-SM actin-positive
      myofibroblasts. In addition, TGF-beta1 and TGF-beta R II were always present, TGF
      beta RII being expressed in both alpha-SM actin-positive and negative
      fibroblastic cells. CONCLUSIONS: Myofibroblast accumulation is a key event in ERM
      associated traction retinal detachment occurring during PVR and PDR. The current
      results suggest that the presence of alpha-SM actin-positive myofibroblasts is
      probably dependent on the concomitant neoexpression of TGF-beta1, TGF-beta RII,
      and ED-A FN. The results furnish new data on the mechanism of alpha-SM actin
      stimulation in fibroblasts in a human pathologic setting.

PMID- 10892882
TI  - Iron, ferritin, transferrin, and transferrin receptor in the adult rat retina.
AB  - PURPOSE: The retina and other tissues need iron to survive. However, the normal
      iron metabolism in rodent retinas had not been characterized. This study was
      intended to investigate iron and iron homeostasis protein (ferritin, transferrin
      [Tf] and transferrin receptor [Tf-R]) distribution in 20- to 55-day-old rat
      retinas. METHODS: Iron was revealed on retinal sections directly by proton
      induced x-ray emission (PIXE) and indirectly by electron microscopy (EM).
      Ferritin, Tf, and Tf-R proteins were localized by immunohistochemistry.
      Transferrin expression was localized by in situ hybridization (ISH). Transferrin
      and ferritin proteins and mRNA were analyzed by Western blot analysis and reverse
      transcription-polymerase chain reaction (RT-PCR), respectively. RESULTS: Iron is
      widely and unevenly distributed throughout the adult rat retina. The highest
      concentration was observed by PIXE in the choroid and the retinal pigmented
      epithelial cell (RPE) layer, and in inner segments of photoreceptors (IS). Outer
      segments of photoreceptors (OS) also contain iron. EM studies suggested the
      presence of iron inclusions inside the photoreceptor discs. Choroid, RPE, and IS
      showed a strong immunoreactivity for ferritin. Transferrin accumulated mainly in
      the IS and OS areas and in RPE cells but can also be detected slightly in retinal
      capillaries. Western blot analysis for Tf and ferritin confirmed their presence
      in the adult neural retina. By RT-PCR, H- and L-chains of ferritin and Tf mRNAs
      were expressed in neural retina, but the main sites of Tf synthesis observed by
      ISH were the RPE and choroid cell layers. Tf-R immunoreactivity was detected in
      the ganglion cell layer, inner nuclear layer, outer plexiform layer, IS, RPE, and
      choroid. These results were similar for all stages studied. CONCLUSIONS: For the
      first time, the present study characterized both iron and iron homeostasis
      proteins in rodent retinas. In the outer retina, iron and ferritin shared the
      same distribution patterns. In contrast, Tf, mainly synthesized by RPE cells and
      detected in OS and IS areas, probably helps to transport iron to photoreceptors
      through their Tf-R. This is a likely pathway for filling iron needs in the outer
      retina.

PMID- 10892883
TI  - Localization of tubby-like protein 1 in developing and adult human retinas.
AB  - PURPOSE: To localize tubby-like protein 1 (TULP1) in developing and adult human
      retinas. METHODS: TULP1 was localized by immunofluorescence microscopy in human
      retinas, aged 8.4 fetal weeks to adult. TULP1-positive cells were identified by
      double labeling with antibodies specific for cones, rods, and astrocytes.
      RESULTS: In adult retinas, anti-TULP1 labels cone and rod inner segments, somata,
      and synapses; outer segments are TULP1-negative. A few inner nuclear and ganglion
      cells are weakly TULP1-positive. In fetal retinas, cells at the outer retinal
      border are TULP1-positive at 8.4 weeks. At 11 weeks, the differentiating central
      cones are strongly TULP1-reactive and some are positive for blue cone opsin. At
      15.4 weeks, all central cones are strongly positive for TULP1 and many are
      reactive for red/green cone opsin. At 17.4 weeks, central rods are weakly TULP
      reactive. In peripheral retina at 15.4 weeks to 1 month after birth, displaced
      cones in the nerve fiber layer are positive for TULP1, recoverin, and blue cone
      opsin. Some ganglion cells are weakly reactive for TULP1 at 11 weeks and later,
      but astrocytes and the optic nerve are TULP1-negative at all ages examined.
      CONCLUSIONS: The finding of TULP1 labeling of cones before they are reactive for
      blue or red/green cone opsin suggests an important role for TULP1 in development.
      TULP1 expression in both developing and mature cones and rods is consistent with
      a primary photoreceptor defect in retinitis pigmentosa (RP) caused by TULP1
      mutations. Weak TULP1-immunolabeling of some inner retinal neurons in developing
      and adult retinas suggests that optic disc changes in patients with RP who have
      TULP1 mutations may be primary as well as secondary to photoreceptor
      degeneration.

PMID- 10892884
TI  - Expression and splicing of FGF receptor mRNAs during APRE-19 cell differentiation
      in vitro.
AB  - PURPOSE: The expression and alternative splicing of the four FGF receptor (FGFR)
      mRNAs are regulated in a developmental- and tissue-specific fashion. Capability
      of differentiation in vitro of the retinal pigment epithelial cell line ARPE-19
      has been previously demonstrated. In this study, the hypothesis that FGF receptor
      gene expression and the alternative splicing of the FGFR1 mRNA is regulated as a
      function of ARPE-19 differentiation in vitro was tested. METHODS: ARPE-19 cells
      were plated at sparse or confluent densities and maintained in culture up to 14
      months. The expression of FGF receptors and the ratio of the FGFR1beta to
      FGFR1alpha splice variants of the FGFR1 transcript were quantified by a published
      PCR technique. Two in vivo samples of human RPE served as controls. RESULTS:
      Sparse cultures of ARPE-19 cells predominantly express FGFR1. When these cultures
      are allowed to differentiate, FGFR2 is also expressed. Samples of mRNA from RPE
      cells in vivo exhibit FGFR1 and FGFR2 expression as well as FGFR3 expression, a
      form that is minimally apparent in vitro. The ratio of the FGFR1beta to
      FGFR1alpha splice variant decreases as a function of cell differentiation in
      vitro and approaches the ratio observed in human RPE cells in vivo. Stimulation
      of cultures in vitro with FGF2 as a prototypical differentiation agent does not
      regulate the ratio of the FGFR1beta to FGFR1alpha splice variant. CONCLUSIONS:
      Differentiation of the ARPE-19 cell line in vitro recapitulates many but not all
      the in vivo patterns of FGFR expression and splicing. This in vitro system may be
      useful for selected studies on how cellular differentiation regulates FGF
      receptor gene expression and splicing.

PMID- 10892885
TI  - Expression of integrin alpha5beta1 and MMPs associated with epithelioid
      morphology and malignancy of uveal melanoma.
AB  - PURPOSE: Altered expression of the alpha5beta1 integrin and matrix
      metalloproteinases (MMPs) is recognized as a hallmark of invasive tumor cells.
      The purpose of the present study was to investigate the expression of integrin
      subunit alpha5, its corresponding ligand fibronectin (FN), and the expression
      pattern for MMPs in four highly proliferative human choroidal melanomas (TP17,
      TP31, SP8.0, and SP6.5) to evaluate whether any correlation can be established
      between these markers and cell tumorigenicity. METHODS: Cell tumorigenicity was
      evaluated by subcutaneous injection of uveal melanoma cell lines in
      immunodeficient nude mice. Anchorage dependency was evaluated by growth assays in
      soft agar. The invasive ability of each cell type was also determined using a
      modified Boyden chamber. Expression of both the alpha5 integrin subunit and FN
      was determined at the mRNA level by RT-PCR. The protein level (for alpha5) was
      determined by flow cytometry and inhibition of adhesion assays by using an
      antibody directed against the alpha5 subunit. Expression of MMPs was determined
      by standard gelatin zymography. RESULTS: Assays in nude mice provided evidence
      that the cell lines possess a range of tumorigenic ability of
      TP17>TP31>SP8.0>SP6.5. Antibody inhibition of cell adhesion and flow cytometry
      demonstrated that TP17 cells have no detectable membrane-bound alpha5beta1,
      whereas low levels are found in primary cultured melanocytes, as well as in
      SP6.5, SP8.0, and TP31 cells. RT-PCR analyses provided evidence that both FN and
      alpha5 expression may be regulated at the transcriptional level. Gelatin
      zymography revealed that all cell lines, as well as normal melanocytes, express
      MMP-2 at varying levels but that only the highly invasive TP17 cell line secretes
      a distinctive MMP with a high molecular weight of 117 kDa. CONCLUSIONS: Among the
      four melanoma cell lines selected for the completion of this study, TP17
      exhibited the most aggressive phenotype, which also correlated with the mostly
      epithelioid morphology of these cells. The cell morphology of the TP17 cell line
      could be related to the loss of alpha5beta1, whereas its invasive properties are
      more likely related to the expression of the 117-kDa MMP.

PMID- 10892886
TI  - Effects of brain-derived neurotrophic factor and neurotrophin-4 on isolated
      cultured retinal ganglion cells: evaluation by flow cytometry.
AB  - PURPOSE: Effects of brain-derived neurotrophic factor (BDNF) and neurotrophin
      (NT)-4 on retinal ganglion cells (RGCs) isolated and cultured in a serum-free
      medium are evaluated objectively by using flow cytometry. METHODS: RGCs from the
      retinas of 2-day-old rats were isolated in a two-step panning and cultured in a
      serum-free medium. BDNF (1, 10, and 100 pg/ml or 1, 10, and 100 ng/ml), NT-4
      (0.1, 1, 10, and 100 ng/ml) or their vehicle, phosphate-buffered saline, were
      individually added to aliquots of the medium to be cultured for 48 hours. Then,
      after adding 5-chloromethylfluorescein diacetate, the survival of RGCs was
      evaluated using flow cytometry. RESULTS: The method used allowed the authors to
      analyze 10,000 RGCs per sample in approximately 2 minutes, so that a much larger
      number of cells was evaluated in a shorter period than with previously reported
      methods. RGCs were classified into either large or small RGCs, and the survival
      of each of these groups was determined objectively by the amount of fluorescent
      emission. BDNF improved the survival rate of RGCs concentration-dependently. In
      particular, the survival rate of small RGCs was greatly improved. BDNF at 100
      ng/ml increased the survival rate of small RGCs by 17.4% and that of large RGCs
      by 7.8% in comparison to the controls. NT4 did not significantly improve the
      survival rates of either large or small RGCs. CONCLUSIONS: BDNF improved the
      survival rate of RGCs, particularly of small RGCs, concentration-dependently, but
      NT-4 had little influence on the survival rate. The current method was useful in
      evaluating the effects of neuroprotective factors or neurotoxic factors on
      cultured RGCs.

PMID- 10892887
TI  - Inhibition of retinal angiogenesis by peptides derived from thrombospondin-1.
AB  - PURPOSE: Thrombospondin (TSP)1 is a tumor suppressor with activity that is
      associated with its ability to inhibit neovascularization. Previous studies have
      mapped this antiangiogenic activity to the type 1 repeats and the amino-terminal
      portion of the molecule within the procollagen-like domain. The present study was
      performed to investigate the ability of TSP-1 and peptides derived from the type
      1 repeats to inhibit retinal angiogenesis. METHODS: TSP-1 and peptides with
      tryptophan-rich, heparin-binding sequences and transforming growth factor (TGF)
      beta1 activation sequences were evaluated in two models of retinal angiogenesis:
      a retinal explant assay and a rat model of retinopathy of prematurity (ROP).
      RESULTS: Platelet-derived TSP-1 inhibited angiogenesis in both experimental
      models. Peptides from the native TSP-1 sequence, which contained both the
      tryptophan-rich repeat and the TGF-beta1 activation sequence, were the most
      potent inhibitors of endothelial cell outgrowth in the retinal explant assay. In
      contrast, a peptide containing only the tryptophan-rich, heparin-binding sequence
      was most active in inhibiting neovascular disease in the rat ROP model.
      CONCLUSIONS: These results indicate that the type 1 repeats of TSP-1 contain two
      subdomains that may independently influence the process of neovascularization,
      and that peptides derived from these type 1 repeats may be promising
      pharmacologic agents for treatment of retinal angiogenesis.

PMID- 10892888
TI  - Selective killing of RPE with a vascular endothelial growth factor chimeric
      toxin.
AB  - PURPOSE: To determine the sensitivity of retinal pigment epithelial (RPE) cells
      to a vascular endothelial growth factor (VEGF) chimeric toxin. METHODS: A
      targeted toxin was developed using recombinant methods to fuse VEGF165 to the
      diphtheria toxin (DT) translocation and enzymatic domain (DT390-VEGF165). Human
      RPE cells, choroidal endothelial cells (CECs), and scleral fibroblasts were
      isolated, and a dose-response for DT390-VEGF165 was determined by measurement of
      cell proliferation and cell number. In parallel experiments, cultures were
      pretreated with transforming growth factor (TGF)-beta2. VEGF-receptor (VEGFR-1
      and -2) expression was determined using reverse transcription-polymerase chain
      reaction and fluorescence-activated cell sorting, and affinity was measured using
      Scatchard analysis. RESULTS: RPE cells and CECs were similarly prone to killing
      by the VEGF-toxin, but scleral fibroblasts were unaffected. Pretreatment with TGF
      beta2 selectively increased the sensitivity of RPE cells to the VEGF-toxin. RPE
      cells expressed both VEGFR-1 and -2 in vitro; however, the expression of VEGFR-1
      was very low. Pretreatment with TGF-beta2 (10 ng/ml) was associated with
      increased expression of the VEGFR-1 in RPE cells and increased receptor affinity
      for VEGF detected by Scatchard analysis. CONCLUSIONS: Dose-dependent killing of
      RPE cells by the DT390-VEGF165 conjugate is selectively enhanced by pretreatment
      with TGF-beta2. This study provides further strong support for the presence of
      functional VEGFRs on human RPE cells, and demonstrates for the first time the
      ability to target a normal nonendothelial cell type through VEGFR expression.

PMID- 10892889
TI  - Mechanisms of aspirin chemoprevention of colorectal cancer.
AB  - Good evidence indicates that the regular consumption of aspirin reduces the risk
      of colorectal cancer by up to 50%. This paper discusses mechanisms for this
      protection and considers carcinogen activation, cell proliferation, apoptosis and
      immune surveillance. It is not clear, however, whether these mechanisms are dose
      related. This question will remain to be answered until the optimum dose and
      duration of aspirin required for protection against colorectal cancer is
      established.

PMID- 10892890
TI  - Chemical substance kinetics in the case of chronobiological variations of
      elimination rate.
AB  - This study describes an approach permitting the determination of compartmental
      concentration and drug kinetics in the case of chronobiological variations of
      elimination rate.

PMID- 10892891
TI  - Determination of human serum semicarbazide-sensitive amine oxidase activity: a
      possible clinical marker of atherosclerosis.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) is present in the plasma membrane of
      several human tissues, e.g. vascular smooth muscle cell adipocytes, and is also
      found in human serum. Some previous studies on cultured endothelial cells
      indicate that cytotoxic metabolites (e.g. hydrogen peroxide, formaldehyde,
      acrolein) formed by serum SSAO may cause endothelial injury and subsequently
      induce atherosclerosis. To investigate the role of this enzyme in the
      pathogenesis of macrovascular complications in diabetes, a simple and sensitive
      radiometric procedure was adapted for human serum measurements. Serum SSAO
      activity of 35 patients with non-insulin dependent diabetes mellitus (NIDDM) and
      that of 30 controls was determined using [14C]-benzylamine as substrate. The
      severity of atherosclerosis was assessed by carotid sonography. Diabetic patients
      with atherosclerosis exhibited a higher SSAO activity compared to diabetic
      patients without complications (212.91 +/- 90.54 pmol/mg protein/h versus 133.17
      +/- 65.40 pmol/mg protein/h, P <0.04). In diabetic patients without
      complications, serum SSAO activity was elevated compared to control subjects
      (133.17 +/- 65.40 pmol/mg protein/h versus 91.79 +/- 31.70 pmol/mg protein/h, P
      <0.01). These results suggest that determination of human serum SSAO activity
      might be a useful marker in the prognostic evaluation of diabetic angiopathy and
      atherosclerosis.

PMID- 10892892
TI  - A study of the production of essential oils in chamomile hairy root cultures.
AB  - The active substances in chamomile (Matricaria recutita L.) belong to chemically
      different structural types. The largest group of medically important compounds
      forming the essential oils are primarily chamazulene, (-)-alpha-bisabolol,
      bisabololoxides, bisabolonoxide A, trans-beta-farnesene, alpha-farnesene,
      spathulenol and the cis/trans-en-in-dicycloethers. Flavonoids, coumarins,
      mucilages, mono- and oligosaccharides also have pharmacological effects. We
      studied the production of essential oils in genetically transformed cultures.
      Sterile juvenile chamomile plants were infected with A4-Y strains of
      Agrobacterium rhizogenes. They are known plant pathogens and are capable of
      inducing so-called hairy roots. The transfer DNA segment of the Ri-virulence
      plasmid of A. rhizogenes becomes integrated in the genome of the plant cells. The
      isolated hairy roots grow rapidly on hormone-free media. In order to obtain
      bacteria-free media, we cultured the transformed roots on Murashige-Skoog (MS)
      medium supplemented with carbenicillin (800 mg/l). To study the production of
      essential oils, the clones were propagated on liquid and solid MS and Gamborg
      (B5) media, respectively. According to gas chromatography, the composition of the
      essential oil of hairy root cultures on different media was found to be similar,
      but differing in proportion. The main component of the essential oil which was
      identified by gas chromatography and mass spectrometry was trans-beta-farnesene,
      as in the intact roots.

PMID- 10892893
TI  - Biologically active compounds of Helichrysum arenarium (L.) Moench.
AB  - The biologically important components of Helichrysum arenarium (L.) Moench are
      the flavonoids, which may have choleretic, hepatoprotective and antimicrobial
      properties. During our study, we examined the flavonoids present in the
      lyophilizate of the inflorescence of Helichrysum arenarium (L.) Moench
      (Helichrysi flos, syn. Stoechados flos) and in the tea made from the
      inflorescence via qualitative and quantitative analysis, and determined the
      flavonoid content. We examined the properties of the lyophilizate antioxidant,
      and measured the H-donor activity, reducing power property and total scavenger
      capacity via spectrophotometric and chemiluminescent methods. We compared the
      results with those of the agent present in milk thistle (Silybum marianum L.),
      the silibinin flavonoid. Regarding the H-donor activity, our lyophilizate was
      determined to be more effective than the silibinin at the same amounts; on the
      other hand, its reducing power property and total scavenger capacity was lower
      than that of silibinin. The flavonoid content, which is responsible for the
      lyophilizate effect, was found to be 0.47% according to our measurements; it is,
      therefore, possible that an extract with such a concentration of flavonoids may
      be of therapeutic benefit.

PMID- 10892894
TI  - Biotransformation of deprenyl enantiomers.
AB  - Rats were treated with either (-)- or (+)-deprenyl, and the metabolites extracted
      from the plasma, liver, kidney and heart homogenates were studied by chiral
      capillary electrophoresis (CE). Stereoselective dealkylation of both optical
      isomers with the formation of desmethyldeprenyl (DD), methamphetamine (MA), and
      amphetamine (A) was found. (-)-MA appears to be the main metabolite of (-)-D, and
      (+)-A for (+)-D. This suggests that the enantiomers undergo a different
      dealkylation process.

PMID- 10892896
TI  - Single dose and multiple dose pharmacokinetics of 2'-fluoro-2',3'
      dideoxyadenosine and 2'-fluoro-2',3'-dideoxyinosine, anti-HIV agents, in rats.
AB  - A single and multiple dose pharmacokinetic (PK) study was conducted in rats
      following oral administration of 2'-fluoro-2',3'-dideoxyadenosine (FddA) and 2'
      fluoro-2',3'-dideoxyinosine (FddI) at three dose levels. Six rats/gender were
      assigned to one of the three FddA or FddI dose levels: 40, 250, and 1000
      mg/kg/day. Three rats/gender were assigned to the PK study on day 1, while the
      remaining 3 rats/gender were assigned to the PK study on day 14. The rats
      received the appropriate doses of either FddA or FddI orally by gavage once a day
      for 14 days. Serial blood samples up to 24 h and cumulative urine samples (0-24
      h) were collected on both days 1 and 14. Plasma and urine samples were analyzed
      for the concentrations of intact FddA and/or FddI using a validated assay. The
      data were subjected to non-compartmental PK analyses. Over the dose range of 40
      1000 mg/kg. both FddA and FddI exhibited dose dependent pharmacokinetics in rats.
      Following FddA administration, there was a rapid and extensive in vivo conversion
      of FddA to FddI; FddI was the major circulating moiety as reflected by Cmax and
      AUC values (generally 2-3-fold greater than those of FddA at each dose level) as
      well as the amount excreted (%UR) in the urine. In contrast, following FddI
      administration, Cmax, AUC, and %UR values were 2-5-fold lower as compared to the
      FddI generated from FddA administration at each dose level, which also suggested
      that FddI was not absorbed as extensively as FddA. Based on the findings of this
      study, FddA is an excellent prodrug of FddI.

PMID- 10892895
TI  - Metabolism of cyclosporine by cytochromes P450 3A9 and 3A4.
AB  - The ability of P450 3A9 to transform cyclosporine was studied and compared to
      that of human P450 3A4. Purified P450 3A4 and P450 3A9 proteins were
      reconstituted in a system containing potassium phosphate buffer, lipids, NADPH
      P450 reductase, and glutathione with NADPH added to initiate the reaction.
      Cyclosporine was added alone and with or without the inhibitors, ketoconazole or
      troleandomycin. High performance liquid chromatography with ultraviolet (HPLC/UV)
      techniques were used to analyze for cyclosporine metabolites. Both P450 3A4 and
      P450 3A9 transformed cyclosporine to three metabolites: AM1, AM9, and AM4n. P450
      3A4 predominantly formed AM1 (63% of metabolites formed) while P450 3A9 formed
      AM4n (59% of metabolites formed). Ketoconazole (0.5 microM) completely inhibited
      P450 3A9 catalyzed formation of AM1 and AM9 and reduced AM4n formation to 28% of
      control. AM4n, AM1, and AM9 formation catalyzed by P450 3A4 was reduced to 50%,
      30%, and 10% of control, respectively, by 0.5 microM ketoconazole. Troleandomycin
      (> 10 microM) inhibited the formation of AM4n by P450 3A4 and P450 3A9 to 60-70%
      of control, while the production of AM1 by P450 3A4 was increased to 120% of
      control and the production of AM1 by P450 3A9 was inhibited to 50% of control.
      Inhibition of P450 3A4 by troleandomycin (> 10 microM) reduced the formation of
      AM9 to 40% of control, but only reduced P450 3A9 formation of AM9 to 80% of
      control. This study shows that rat P450 3A9 is capable of transforming
      cyclosporine to multiple metabolites similar to those generated by human P450
      3A4.

PMID- 10892897
TI  - Bioavailability and bioequivalence of etonogestrel from two oral formulations of
      desogestrel: Cerazette and Liseta.
AB  - In a three-period cross-over study with 24 healthy young females (study part 1),
      the bioavailability of etonogestrel (3-ketodesogestrel) was determined after a
      single oral dose of two Cerazette tablets (each containing 75 microg
      desogestrel), one Liseta tablet (containing 150 microg desogestrel and 1.5 mg
      17beta-estradiol), and an intravenous dose of 150 microg etonogestrel.
      Etonogestrel serum levels from 23 subjects could be analysed by radio
      immunoassay. The geometric mean bioavailability of etonogestrel from Cerazette
      and Liseta tablets was 0.79 and 0.82, with 95% confidence intervals of 0.73-0.86
      and 0.76-0.88, respectively. Also, the oral formulations were found to be
      bioequivalent. Subsequently, the single-dose pharmacokinetic parameters of
      etonogestrel from Cerazette tablets were compared with those after multiple
      dosing of one Cerazette tablet once daily for 7 days, in a subgroup of 12
      subjects (study part 2). A steady state was observed from the fourth day of daily
      dosing onwards, with time-invariant parameters except for a 14% lower dose
      normalised AUC. The least-squares geometric means of the elimination half-life of
      etonogestrel were approximately 30 h for the three single-dose treatments in
      study part 1, as well as for the single- and multiple-dose treatments of
      Cerazette in study part 2, without differences between groups.

PMID- 10892898
TI  - Diclofenac metabolic profile following in vitro percutaneous absorption through
      viable human skin.
AB  - The extent of metabolism of diclofenac sodium in excised viable human skin was
      investigated using combination HPLC and radioactivity assay. In an earlier
      diffusion experiment using an in vitro flow-through diffusion system,
      radiolabelled diclofenac sodium in either lotion (Pennsaid) or aqueous solution
      was applied to viable human skin, either as single dose or multiple dose (8 times
      over 2 days). In this study, the receptor fluid samples from the diffusion
      experiment were subjected to extraction and the aliquot was analysed using HPLC
      to separate diclofenac and authentic metabolites. Based on the radioactivity of
      each HPLC fraction, the collection time of the fractions was compared with the
      retention time of diclofenac and metabolites in standard solutions. The samples
      from a single or multiple dose application of lotion showed radioactivity in
      mainly one fraction, whose retention time corresponded with diclofenac. Other
      HPLC fractions showed none or only small amounts of radioactivity within the
      error range of the assay. The same results were obtained with the pooled samples
      from the application of the lotion or of aqueous solution. The results suggest
      that diclofenac sodium does not undergo metabolism in viable human epidermis
      during percutaneous absorption in vitro. Hence, with topical application to human
      skin in vivo, diclofenac will be delivered with minimal, if any, metabolism.

PMID- 10892899
TI  - Effects of dietary broccoli on rat testicular xenobiotic metabolizing enzymes.
AB  - The effects of vegetables on the activities of various metabolizing enzymes in
      liver and intestine have been studied intensively, whereas studies on effects on
      testicular metabolizing enzymes are lacking. The present report is the first
      describing the effects of dietary broccoli on the activities of a number of
      xenobiotic metabolizing enzymes from rat testes. Groups of male Wistar rats were
      fed a semisynthetic diet with 10% (w/w) freeze-dried broccoli for 1 week.
      Different broccoli samples with varying content of glucosinolates were used.
      Dietary broccoli significantly increased the activities of two testicular phase
      II enzymes--glutathione S-transferase (1.6-fold) and UDP-glucuronosyl transferase
      (1.8-fold). The activities of these enzymes differed significantly depending on
      the conditions during cultivation of the broccoli, because of differences in the
      content of glucosinolates and other secondary plant metabolites. The levels of
      two glutathione S-transferase subunits, rGSTM2 and rGSTA, were determined using
      Western blotting analysis and the levels of both subunits were reduced in animals
      fed broccoli grown at low S-fertilizer level. Broccoli did not statistically
      significantly modulate the activities of the phase I enzymes, epoxide hydrolase
      or NAD(P)H quinone-oxidoreductase, or the phase II enzyme p-sulphotransferase, or
      the anti-oxidative enzymes catalase and total glutathione peroxidase in rat
      testes. In general, dietary broccoli affects phase I and phase II enzyme levels
      in rat testes much less than found in liver, however, two rat testicular phase II
      xenobiotic metabolizing enzymes were induced.

PMID- 10892900
TI  - Is an optimal mitral substitute within reach?

PMID- 10892901
TI  - The right person for the job.

PMID- 10892902
TI  - Ralph D. Alley lecture. The hammer, the sickle, and the scalpel: a cardiac
      surgeon's view of Eastern Europe.

PMID- 10892903
TI  - Paget-Schroetter syndrome: what is the best management?
AB  - BACKGROUND: The evaluation of 312 extremities in 294 patients with Paget
      Schroetter syndrome (effort thrombosis of the axillary-subclavian vein) over 30
      years provides the basis for optimal management determination. METHODS AND
      RESULTS: Group I (35 extremities) was initially treated with anticoagulants only.
      Twenty-one developed recurrent symptoms after returning to work, requiring
      transaxillary resection of the first rib. Thrombectomy was necessary in eight.
      Group II (36 extremities) was treated with thrombolytic agents initially, with 20
      requiring subsequent rib resection after returning to work. Thrombectomy was
      necessary only in four. Of the most recent 241 extremities (group III), excellent
      results accrued using thrombolysis plus prompt first rib resection for those
      evaluated during the first month after occlusion (199). The results were only
      fair for those if seen later than 1 month (42). CONCLUSIONS: An early diagnosis
      (less than 1 month), expeditious thrombolytic therapy, and prompt first rib
      resection are critical for the best results.

PMID- 10892904
TI  - Comparison of clinical results for unilateral and bilateral thoracoscopic lung
      volume reduction.
AB  - BACKGROUND: It is widely believed that bilateral thoracoscopic lung volume
      reduction (BTLVR) yields superior results when compared with unilateral
      thoracoscopic lung volume reduction (UTLVR) with regard to spirometry, functional
      capacity, oxygenation and quality of life results. METHODS: To address these
      issues, we compared the results of patients undergoing UTLVR (N = 338 patients)
      and BTLVR (N = 344 patients) from 1993 to 1998 at five institutions. Follow-up
      data were available on 671 patients (98.4%) between 6 and 12 months after
      surgery, and a patient self-assessment was obtained at a mean of 24 months.
      RESULTS: It was found that BTLVR provides superior improvement in measured
      postoperative percent change in FEV1 (L) (UTLVR 23.3% +/- 55.3 vs BTLVR 33% +/-
      41, p = 0.04), FVC(L) (10.5% +/- 31.6 vs 20.3% +/- 34.3, p = 0.002) and RV(L) (
      13% +/- -22 vs -22% +/- 17.9, p = 0.015). BTLVR also provides a slight
      improvement over UTLVR in patient's perception regarding improved quality of life
      (UTLVR 79% vs BTLVR 88%, p = 0.03) and dyspnea relief (71% vs 61%, p = 0.03).
      There was no difference in mean changes in PO2 (mm Hg) (UTLV 4.5 +/- 12.3 vs
      BTLVR 4.9 +/- 13.3, p = NS), 6-minute walk (UTLVR 26% +/- 66.1 vs BTLVR 31% +/-
      59.6, p = NS) or decreased oxygen utilization (UTLVR 78% vs BTLVR 74%, p = NS).
      CONCLUSIONS: These data suggest that both UTLVR and BTLVR yield significant
      improvement, but the results of BTLVR seem to be superior with regard to
      spirometry, lung volumes, and quality of life.

PMID- 10892905
TI  - Oncogenic ras results in increased cell kill due to defective thermoprotection in
      lung cancer cells.
AB  - BACKGROUND: The survival response of normal cells to heat stress is an
      upregulation of heat shock proteins and ras protein activation. We hypothesized
      that in lung cancer cells the presence of oncogenic ras interferes with
      thermoprotective mechanisms resulting in cell death. METHODS: An equal number of
      lung tissue culture cells (normal and cancerous) were subjected to either heat
      stress and then recovery (43 degrees C for 180 minutes, 37 degrees C for 180
      minutes) or recovery alone (37 degrees C for 360 minutes). End points were
      surviving number of cells, cell-death time course, heat shock protein (HSP70,
      HSC70, HSP27) expression before and after heat stress, and time course for HSP70
      expression during heat stress and recovery. Heated cells were compared with
      unheated control cells, then this difference was compared between cell types.
      RESULTS: Heat stress in normal cells caused an 8% decrease in cell number versus
      a 78% +/- 5% decrease in cancer cells (p < 0.05). In normal cells, heat stress
      caused a 4.4-fold increase in HSP70, no change in HSC70, and a 1.7-fold increase
      in HSP27. In contrast, cancer cells initially contained significantly less HSP70
      (p < 0.05), and there was a 27-fold increase in HSP70 and a 2-fold increase in
      HSC70 with no HSP27 detected (comparison significant, p < 0.05). HSP70 time
      course in normal cells showed that HSP70 increased 100-fold, reaching a vertex at
      2 hours and remaining elevated for 24 hours; in cancer cells, HSP70 maximum
      expression (100-fold) peaked at 5 hours,,then decreased to slightly elevated at
      24 hours. CONCLUSIONS: Cancer cells with oncogenic ras have defective
      thermoprotective mechanism(s) causing increased in vitro cell death, which
      provides an opportunity for thermal treatment of lung cancer.

PMID- 10892906
TI  - Reperfusion injury significantly impacts clinical outcome after pulmonary
      transplantation.
AB  - BACKGROUND: Reperfusion injury after pulmonary transplantation can contribute
      significantly to postoperative pulmonary dysfunction. We hypothesized that
      posttransplantation reperfusion injury would result in an increase in both in
      hospital mortality and morbidity. We also hypothesized that the incidence of
      reperfusion injury would be dependent upon the cause of recipient lung disease
      and the interval of donor allograft ischemia. METHODS: We performed a
      retrospective study of all lung transplant recipients at our institution from
      June 1990 until June 1998. One hundred patients received 120 organs during this
      time period. We compared two groups of patients in this study: those experiencing
      a significant reperfusion injury (22%) and those who did not (78%). RESULTS: In
      hospital mortality was significantly greater in patients experiencing reperfusion
      injury (40.9% versus 11.7%, p < 0.02). Posttransplantation reperfusion injury
      also resulted in prolonged ventilation (393.5 versus 56.8 hours, p < 0.001) and
      an increased length of stay in both the intensive care unit (22.2 versus 10.5
      days, p < 0.01) and in the hospital (48.8 versus 25.6 days, p < 0.03). The
      incidence of reperfusion injury could not be attributed to length of donor organ
      ischemia (221.5 versus 252.9 minutes, p < 0.20). The clinical impact of
      reperfusion injury was significantly greater in patients undergoing
      transplantation for preexisting pulmonary hypertension (6/14) than those with
      chronic obstructive pulmonary disease or emphysema alone (6/54) (42.9% versus
      11.1%, p < 0.012). CONCLUSIONS: Clinically significant pulmonary reperfusion
      injury increased in-hospital mortality and morbidity resulting in prolonged
      ventilation, length of stay in the intensive care unit, and cost of
      hospitalization. The incidence of reperfusion injury was not dependent upon the
      duration of donor organ ischemia but increased with the presence of preoperative
      pulmonary hypertension. These findings suggest that recipient pathophysiology and
      donor allograft quality may play important roles in determining the incidence of
      reperfusion injury.

PMID- 10892907
TI  - Effect of mast cells on tumor angiogenesis in lung cancer.
AB  - BACKGROUND: We conducted a retrospective study to clarify the effect of mast
      cells on tumor angiogenesis in lung cancer patients. METHODS: Formalin-fixed and
      paraffin-embedded tumor sections were used in this study. Parenchymal mast cells
      were stained with Alcian blue and safranin O. The number of mast cells per ten
      fields at a magnification of 200x was counted under light microscopy, and the
      average count was determined. To highlight the microvessels, endothelial cells
      were stained with anti-human factor VIII antibody. After the microvessel count
      was determined, the microvessels were further stained with Alcian blue and
      safranin O to show areas of mast cell infiltration. Expression of vascular
      endothelial growth factor was assessed using a polyclonal antibody. RESULTS: We
      found a significant correlation between mast cell count and microvessel density.
      This correlation was also observed in patients with adenocarcinoma (p < 0.001) as
      well as in patients with squamous cell carcinoma (p < 0.01). Double staining of
      the microvessels showed highly angiogenic areas densely populated with mast
      cells. Although we detected a slight trend toward a correlation between vascular
      endothelial growth factor expression and microvessel density, it was not
      statistically significant. We found no association between vascular endothelial
      growth factor expression and mast cell count. CONCLUSIONS: There appears to be a
      direct correlation between the number of mast cells and tumor angiogenesis in
      patients with lung cancer, and this relationship appears to be independent of
      vascular endothelial growth factor expression.

PMID- 10892908
TI  - Artificial lymphogenous metastatic model using orthotopic implantation of human
      lung cancer.
AB  - BACKGROUND AND METHODS: We established a new, patientlike orthotopic model of
      lung cancer metastasis with human non-small cell lung cancer cell lines. In this
      report, we describe the progressive stages of development of lymphogenous
      mediastinal metastasis in the Ma44-3 cell line from day 3 to day 15 after
      implantation in severe combined immunodeficiency mice and the process of
      lymphogenous metastasis. RESULTS: All mice killed after day 12 had perivascular
      and peribronchial tumor growth. Micrometastasis to the mediastinum was first
      observed on day 5. On days 5 through 9, 10 of 13 mice had metastasis to the
      mediastinum, and all mice had one by day 12. When perivascular and peribronchial
      tumor growth was present by day 5, metastasis to the mediastinum developed in all
      mice. CONCLUSIONS: This study demonstrates the lymphogenous spread of human lung
      cancer in severe combined immunodeficiency mouse using an orthotopic implantation
      model. Our model was thought to be an artificial lymphogenous metastasis model,
      owing to forced tumor inoculation into lymphatic vessels.

PMID- 10892909
TI  - Who should follow up lung cancer patients after operation?
AB  - BACKGROUND: It is unclear whether follow-up by a thoracic surgeon after lung
      cancer resection alters survival. METHODS: The charts of 245 early stage (< or =
      IIB) non-small cell lung cancer patients, diagnosed between 1988 and 1995, were
      reviewed. Follow-up data were complete to January 1, 1997, in 96.3% (236 of 245)
      of cases. RESULTS: Ninety of the 111 recurrences were detected before discharge
      from the thoracic clinic. Despite clinic follow-up, 66.7% (60 of 90) were
      identified by the family physician, and only 28.9% (26 of 90) by the surgeon. The
      remaining 4.4% (4 of 90) were detected by other physicians. Ninety-six percent
      (25 of 26) surgeon-detected recurrences had suspicious clinical or chest
      radiographic findings, compared with 92% for family physician-detected
      recurrences (55 of 60; not significant). The cost per recurrence detected by
      surgeons was Can $4,367. A 75% cost savings could ensure if patients were
      followed up by their family physician. There was no 5-year survival benefit for
      patients whose recurrence was detected by the surgeon. CONCLUSIONS: Long-term
      follow-up after limited-stage non-small cell lung cancer resection could possibly
      be performed by a family physician alone without compromising overall survival,
      and with significant cost savings.

PMID- 10892910
TI  - Revascularization of canine cryopreserved tracheal allografts.
AB  - BACKGROUND: We examined the blood supply of a cryopreserved tracheal allograft
      and its morphohistologic changes after transplantation. METHODS: In each of 22
      dogs, a five-ring tracheal segment was replaced by one of the following tracheal
      grafts: fresh autografts (n = 8), cryopreserved tracheal allografts (n = 8), or
      fresh allografts (n = 6). The cryopreserved tracheal allografts were preserved at
      -196 degrees C for 60 days. No immunosuppressant was given to any of the animals.
      All grafts were retrieved at 1 and 12 weeks and assessed by microangiography and
      histology. RESULTS: The epithelial denudation and the revascularization of the
      transverse intercartilaginous arteries were recognized within 7 days as common to
      each of the three types of grafts. In the cryopreserved tracheal allografts,
      neither cartilage degradation nor graft shrinkage occurred at 7 days. However,
      the recanalized transverse intercartilaginous arteries completely disappeared at
      12 weeks, and marked shrinkage occurred; the cartilage cells were accompanied by
      karyolysis and were significantly decreased in number (p < 0.05). Recanalization
      of the transverse intercartilaginous arteries was also demonstrated in the fresh
      allografts; however, necrosis abruptly occurred as a result of acute rejection
      responses. CONCLUSIONS: Cryopreservation of a tracheal allograft provided
      sufficient reduction of the acute rejection responses, and blood supply to the
      cryopreserved tracheal allograft was established through the recanalized
      transverse intercartilaginous arteries within 7 days; however, subsequent chronic
      rejection responses resulted in occlusion of the transverse intercartilaginous
      arteries and atrophy.

PMID- 10892911
TI  - Perforation of Barrett's ulcer: a challenge in esophageal surgery.
AB  - BACKGROUND: Barrett's ulcer, which develops within Barrett's esophagus, is
      frequently responsible for bleeding. Perforation is a rare complication
      constituting a great challenge for diagnosis and management. METHODS: Three
      personal cases and 31 published reports of perforated Barrett's ulcer were
      reviewed retrospectively. The site of perforation, clinical presentation,
      management, and outcome were assessed. RESULTS: The clinical presentation proved
      to be heterogeneous and was determined by the site of perforation: this was the
      pleural cavity (20% of cases), mediastinum (20%), left atrium (16.6%),
      tracheobronchial tract (13.3%), aorta (13.3%), pericardium (10%), or pulmonary
      vein (6.6%). Early esophagectomy and esophageal diversion-exclusion were the most
      frequent procedures, and overall mortality was 45%. CONCLUSIONS: The poor
      prognosis of perforated Barrett's ulcer should be improved by earlier diagnosis
      and adequate emergent operation. Although early esophagectomy constitutes the
      recommended procedure, esophageal diversion-exclusion, which allows control of
      both sepsis and bleeding, is also of interest.

PMID- 10892912
TI  - Predictors of perioperative morbidity and mortality in lung volume reduction
      surgery.
AB  - BACKGROUND: Selection criteria for lung volume reduction surgery are still being
      refined. We sought to determine whether preoperative features could be used to
      predict early morbidity or mortality. METHODS: We reviewed preoperative
      characteristics of the first 89 patients who underwent lung volume reduction
      surgery at the Alfred Hospital. Data included arterial blood gases, prednisolone
      use, pulmonary function tests, 6-minute walk test, and anesthetic time. Length of
      stay and reintubation for respiratory failure were used as markers of morbidity.
      RESULTS: Findings included PaCO2 of 43 +/- 0.7 mm Hg, PaO2 70 +/- 1.1 mm Hg,
      percent predicted values for forced expiratory volume in 1 second 29.6% +/- 0.8%,
      TLCO% predicted 35.2 +/- 1.4%, and 6-minute walk test of 315 +/- 10.6 m (mean +/-
      SEM). Mean length of stay was 19 +/- 2 days, with 17 (19%) patients reintubated
      for respiratory failure. Mortality rate was 5.6% at 1 year post surgery, with no
      deaths in patients less than 65 years old. Multivariate analysis revealed that
      length of stay, reintubation and mortality were predicted by age and surgical
      time (p < 0.05), with no correlation with any other variables tested. Age greater
      than 70 years was associated with a significant risk of mortality (OR 9.0; p =
      0.04). CONCLUSIONS: Age greater than 70 years and anesthetic time greater than
      210 minutes predict both perioperative morbidity and mortality.

PMID- 10892913
TI  - One-stage approach for retroperitoneal and mediastinal metastatic testicular
      tumor resection.
AB  - BACKGROUND: Eight percent of nonseminomatous germ cell tumors of the testis are
      associated with postchemotherapy residual masses in both the retroperitoneum and
      the posterior mediastinum. We describe a transabdominal transdiaphragmatic
      approach that allows simultaneous resection of these masses. METHODS: After
      standard retroperitoneal lymph node dissection through a midline laparotomy, an
      incision parallel to the right crus of the diaphragm was made and extended
      anteriorly through the muscular portion. Excellent exposure of the lower
      posterior mediastinum was obtained. Masses located higher than vertebra T8 were
      resected by extending this incision anteriorly and performing a partial sternal
      division. A complete median sternotomy can be done to allow subcarinal
      dissection, as well as pulmonary or anterior mediastinal mass resection. RESULTS:
      Between 1993 and 1999, 18 patients had simultaneous resection of retroperitoneal
      and posterior mediastinal masses with this approach. There were no perioperative
      deaths; 3 patients had minor postoperative complications. After a median follow
      up of 3.2 years, the overall 5-year survival rate was 92%, and the 5-year disease
      free survival rate was 87%. CONCLUSIONS: The transdiaphragmatic approach to the
      posterior mediastinum is less aggressive than the thoracoabdominal approach. It
      is safe and effective for simultaneous resection of postchemotherapy testicular
      nonseminomatous germ cell tumors located in the retroperitoneum and posterior
      mediastinum.

PMID- 10892914
TI  - Pleural tent after upper lobectomy: a prospective randomized study.
AB  - BACKGROUND: The aim of the present study was to assess the cost/efficacy of the
      pleural tent procedure after upper lobectomy. METHODS: A prospective randomized
      analysis was performed on 50 patients submitted to upper lobectomy and divided
      into two groups: group 1 (25 patients) with pleural tent; group 2 (25 patients)
      without pleural tent. RESULTS: The univariate comparison between the two groups
      did not show any significant difference in terms of age, gender, spirometry,
      smoking history, chronic obstructive pulmonary disease index, side of tumor,
      arterial oxygen tension, arterial carbon dioxide tension, size and location of
      tumor, presence of pleural adhesions, length of the stapled parenchyma, and
      operative time. Pleural tent significantly reduced the days of postoperative air
      leak (1.2 versus 5.8, p = 0.01), chest tubes (5.4 versus 10.4, p = 0.01), and
      hospital stay (6.9 versus 10.8, p = 0.01). Moreover, no difference was noted
      between the two groups in terms of pleural effusion in the first postoperative 48
      hours, need of postoperative blood transfusion, and occurrence of other
      complications. CONCLUSIONS: Pleural tenting after upper lobectomy is a safe and
      effective procedure and its routine use is warranted.

PMID- 10892915
TI  - Does multivessel, off-pump coronary artery bypass reduce postoperative morbidity?
AB  - BACKGROUND: Off-pump coronary artery bypass (OPCAB) is an emerging procedure. It
      is assumed that elimination of cardiopulmonary bypass for coronary artery bypass
      grafting has the potential for reducing postoperative morbidity. This review
      evaluates the safety and impact of multivessel OPCABG as compared to CABG.
      METHODS: A retrospective review of 744 patients undergoing multivessel coronary
      artery bypass between January 1, 1997, and March 31, 1999, was done. The total
      population was divided into two groups: group A (n = 609 cardiopulmonary bypass)
      and group B (n = 135 OPCAB). This consecutive study cohort was elective status,
      full sternotomy with three or more distal anastomoses performed at a single
      institution. RESULTS: The mean risk adjusted predicted mortality was 2.3% in
      group A and 2.7% in group B (p = NS), with the mean number of distal anastomosis
      being greater in group A (3.8 vs 3.5/patient, p < 0.001). Major postoperative
      complications were similar but were not statistically significant between groups.
      Postoperative blood loss and use of blood transfusions were the only significant
      variables (p < 0.001). CONCLUSIONS: Multivessel OPCABG can be safely performed in
      selected patients. Elimination of cardiopulmonary bypass did not significantly
      reduce postoperative morbidity. Prospective randomized trials and long-term
      follow-up are needed to better define patient selection and the role of OPCABG.

PMID- 10892916
TI  - Long-lasting improvement after septal myectomy for hypertrophic obstructive
      cardiomyopathy.
AB  - BACKGROUND: The most effective treatment of symptomatic patients with
      hypertrophic obstructive cardiomyopathy is still disputed. Treatment options
      include medical therapy, pacemaker insertion, percutaneous transluminal septal
      myocardial ablation, mitral valve replacement, and surgical resection of
      obstructing muscle. The long-term results of the various treatment options are
      not well defined. We aimed to demonstrate that septal myectomy is efficacious in
      reducing or abolishing left ventricular outflow tract gradient and leads to long
      lasting symptomatic improvement in most patients. METHODS: Twenty-two consecutive
      patients had septal myectomy between 1981 and the present. Their records were
      reviewed to document the details of their preoperative status, hospital course,
      their subsequent clinical outcome, and current status. RESULTS: Mean age at
      operation was 31.3 years. Preoperatively all patients were disabled by typical
      symptoms despite aggressive medical treatment. Mean resting gradient was 78 mm
      Hg. Nine patients required simultaneous associated cardiac procedures. There were
      no perioperative deaths and minimal morbidity. Two patients died at 6 and 9 years
      postoperatively of congestive heart failure and arrhythmias. Long-term survivors
      have been followed up for a mean of 6.6 years. Currently all have minimal or no
      symptoms. The mean resting gradient was 12 mm Hg. No patient has required
      reoperation for residual obstruction. CONCLUSIONS: Septal myectomy reduces or
      abolishes left ventricular outflow tract gradient in hypertrophic obstructive
      cardiomyopathy. Myectomy provides long-lasting symptomatic improvement in most
      patients. The clinical status of patients late postoperatively can be affected by
      arrhythmias and myocardial dysfunction.

PMID- 10892917
TI  - Long-term angiographic results of coronary endarterectomy.
AB  - BACKGROUND: To evaluate the long-term patency of endarterectomized coronary
      vessels, we studied patients having recatheterization after coronary artery
      bypass grafting. METHODS: Forty-one clinical and angiographic variables were
      analyzed in 97 study patients who had coronary endarterectomy (CE) and in 154
      control patients who did not have CE but who had repeat catheterization after
      coronary artery bypass grafting. RESULTS: Ninety-seven patients had 132 CEs. The
      right coronary artery was the most commonly endarterectomized vessel (73 of the
      132 endarterectomized vessels). At a mean of 7.1 years of follow-up,
      significantly fewer bypass grafts to endarterectomized vessels were patent
      compared with nonendarterectomized vessels (40% of endarterectomized vessels
      compared with 58% of nonendarterectomized vessels in study patients and 65% in
      control patients, p = 0.0003). The only predictor of long-term CE graft patency
      is age-adjusted body surface area (p = 0.0068). Patency in grafts to
      nonendarterectomized vessels is diminished by hypertension (p = 0.046) and
      current cigarette use (p = 0.024) and improved by use of mammary artery grafting
      (p < 0.0001). CONCLUSIONS: These results show that long-term patency in bypass
      grafts to endarterectomized vessels is less common than in nonendarterectomized
      vessels and that this patency is related to larger body size. Patency in
      nonendarterectomized vessels is reduced by risks of arteriosclerosis. This
      suggests that CE should be used with caution in smaller patients and that
      aggressive control of risk factors for atherogenesis is particularly important in
      patients who have CE. On the basis of these results, we speculate that the extent
      of disease is advanced in patients who require CE.

PMID- 10892918
TI  - Retrograde perfusion with a sodium channel antagonist provides ischemic spinal
      cord protection.
AB  - BACKGROUND: Neuronal voltage-dependent sodium channel antagonists have been shown
      to provide neuroprotection in focal and global cerebral ischemic models. We
      hypothesized that retrograde spinal cord venous perfusion with phenytoin, a
      neuronal voltage-dependent sodium channel antagonist, would provide protection
      during prolonged spinal cord ischemia. METHODS: In a rabbit model, spinal cord
      ischemia was induced for 45 minutes. Six groups of animals were studied. Controls
      (group I, n = 8) received no intervention during aortic cross-clamping. Group II
      (n = 8) received systemic phenytoin (100 mg). Group III (n = 4) received systemic
      phenytoin (200 mg). Group IV (n = 8) received retrograde infusion of room
      temperature saline (22 degrees C) only. Group V (n = 8) and group VI (n = 9)
      received retrograde infusion of 50 mg and 100 mg of phenytoin, respectively,
      (infusion rate: 0.8 mL x kg(-1) x min(-1) during the ischemic period). Mean
      arterial blood pressure was monitored continuously. Animals were allowed to
      recover for 24 hours before assessment of neurologic function using the Tarlov
      scale. RESULTS: Tarlov scores (0 = complete paraplegia, 1 = slight lower limb
      movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop)
      were as follows (mean +/- SEM): group I, 0.50 +/- 0.50; group II, 0.25 +/- 0.46;
      group IV, 1.63 +/- 0.56; group V, 4.13 +/- 0.23; and group VI, 4.22 +/- 0.22 (p <
      0.0001 V, VI versus I, II, IV by analysis of variance). No differences in mean
      arterial blood pressure were observed. All animals in group III became profoundly
      hypotensive and died before the conclusion of the 45-minute ischemic time.
      CONCLUSIONS: Retrograde venous perfusion of the spinal cord with phenytoin, a
      voltage-sensitive sodium channel blocker, is safe and provides significant
      protection during prolonged spinal cord ischemia.

PMID- 10892919
TI  - Differences in myocardial and peripheral VEGF and KDR levels after acute
      ischemia.
AB  - BACKGROUND: Recent clinical use of vascular endothelial growth factor (VEGF) in
      the treatment of both myocardial and peripheral ischemia has suggested the
      possibility of tissue specific coregulation of VEGF and its receptors (eg, kinase
      domain region [KDR]). The present study was performed to detect the relationship
      between VEGF and KDR protein levels after acute myocardial and peripheral
      ischemia. METHODS: Eleven dogs were divided into two groups: peripheral ischemia
      (n = 6, ligation of major limb arteries) and myocardial ischemia (n = 5,
      circumflex artery ligation). Muscle biopsy specimens were taken from the
      perfusion territories of the occluded circumflex artery and limb arteries 3 hours
      and 6 hours after ligation. Protein levels were determined using Western blot
      analysis. RESULTS: In myocardium, VEGF levels increased on average eightfold from
      baseline (p < 0.05) both 3 hours and 6 hours after occlusion, whereas myocardial
      KDR levels dropped by about 60% at 3 hours and 80% at 6 hours (p < 0.05). With
      limb ischemia, both VEGF and KDR levels were significantly elevated at 3 hours.
      CONCLUSIONS: In acute ischemia, regulation of VEGF and KDR may be controlled
      differently in cardiac and skeletal muscle. Myocardial KDR levels showed a
      significant decrease from baseline compared with a significant rise with
      peripheral ischemia.

PMID- 10892920
TI  - Predictors of adverse outcome and transient neurological dysfunction after
      ascending aorta/hemiarch replacement.
AB  - BACKGROUND: This study was undertaken to determine predictors of adverse outcome
      and transient neurological dysfunction after replacement of the ascending aorta
      with an open distal anastomosis. METHODS: All 443 patients (300 male, median age
      63) undergoing replacement of the ascending aorta with an open distal anastomosis
      between 1986 and 1998 were included in the analysis. The ascending aorta alone
      was replaced in 190 (42.9%); 253 (57.1%) also had proximal arch replacement.
      Median hypothermic circulatory arrest (HCA) time was 25 minutes (range 12 to 68).
      Either death or permanent neurological dysfunction were considered adverse
      outcome (AO). RESULTS: Adverse outcome occurred in 11.5% (51 of 443) of patients
      overall: in 7.4% of elective (20 of 269) or urgent (4 of 54) operations, but in
      17% (19 of 113) of emergencies. Multivariate analysis of the group as a whole
      revealed that significant (p < 0.05) independent preoperative predictors of AO
      were age greater than 60 [odds ratio (OR) 2.2], hemodynamic instability (OR 2.7),
      and dissection (OR 1.9). For the 435 operative survivors, procedural variables
      predictive of AO were contained rupture (OR 2.8) and HCA time (OR 1.03/min). When
      only the 271 elective patients were analyzed separately, the need for a
      concomitant procedure (p = 0.009, OR 3.6) and HCA time (p = 0.002, OR 1.06/min)
      were the only predictors of AO in multivariate analysis. Transient neurological
      dysfunction (TND) occurred in 86 of 392 patients (22%). Significant predictors of
      TND for all patients without AO were age (OR 1.06/y), HCA time (OR 1.04/min),
      coronary artery disease (OR 2.2), hemodynamic instability (OR 3.4), and acute
      operation (OR 2.2). Survival of discharged patients was 93% at 1 year and 83% at
      5 years. CONCLUSIONS: Early elective operation and shorter HCA time during
      ascending aorta/hemiarch surgery will reduce both AO and TND.

PMID- 10892921
TI  - Late complications of tissue glues in aortic surgery.
AB  - BACKGROUND: Tissue glues are used in cardiothoracic surgery as an adjunct to
      operative procedures where tissues are frail, as in aortic dissection, or where
      added hemostasis is required. This study was undertaken to review the use of
      tissue glue in our institution over a 5.5-year period. The aim of the study was
      to identify any potentially glue-related complications. METHODS: A review of
      tissue glue use for the period from January 1993 to September 1998 was performed
      and pre-, intra-, and postoperative parameters were collected. After some unusual
      surgical findings, of special interest was a range of pathology found at late
      reoperation. RESULTS: A total of 67 cases of tissue glue use were identified,
      with the majority of operations for type A dissection (76%). There were two
      intraoperative deaths. Twenty-seven of 65 patients (41%) required 29 further open
      chest operations; of these, 17 were for acute problems of bleeding or tamponade.
      Twelve patients (18%) underwent late reoperations months to years later. Nine of
      these patients, concentrated in two operative groups (7 patients with aortic
      valve resuspension and 2 patients who had undergone "switch" operations for
      transposition of great vessels), displayed complications related to the
      application of gelatin-resorcinol-formaldehyde (GRF) tissue glue. CONCLUSIONS:
      Indications for tissue glues in cardiothoracic surgery must be carefully
      considered. We have reviewed our use of some tissue glues in acute type A aortic
      dissections and in pediatric cardiac patients and have discontinued the use of
      GRF glues because of unsatisfactory long-term complications.

PMID- 10892922
TI  - The heart reinnervates after transplantation.
AB  - BACKGROUND: Whether cardiac reinnervation occurs after transplantation remains
      controversial. If reinnervation does occur, how sympathetic and parasympathetic
      efferent neurons do this remains unknown. METHODS: Power spectral analysis of
      heart rate variability was assessed for 1 year after cardiac autotransplantation
      in 9 dogs. After induction of anesthesia 13 months after transplantation, cardiac
      and intrinsic cardiac neuronal responses elicited by both electrical stimulation
      of parasympathetic or sympathetic efferent neurons and systemic or local coronary
      artery administration of nicotine (5 microg/kg), angiotensin II (0.75 microg/kg),
      and tyramine (1.2 microg/kg) were studied. The transmembrane electrical
      properties of intrinsic cardiac neurons were studied in vitro. Ventricular tissue
      catecholamine content, alpha-tubulin expression, and beta-adrenergic receptor
      density and affinity were studied. The presence of axons crossing suture lines
      was sought histologically. RESULTS: Nerves were identified crossing suture lines.
      Electrical or chemical (ie, nicotine or angiotensin II) activation of sympathetic
      efferent neurons enhanced cardiodynamics, as did tyramine. Stimulating vagal
      efferent preganglionic axons induced bradycardia in half of the dogs. Functional
      reinnervation did not correlate with specific power spectra derived from rate
      variability in the conscious state. Responding to nicotine and angiotensin II in
      situ, transplanted intrinsic cardiac neurons generated spontaneous activity.
      These neurons displayed nicotine-dependent synaptic inputs in vitro. Ventricular
      tissue had normal beta-adrenergic receptor affinity and density but reduced
      catecholamine and alpha-tubulin contents. CONCLUSIONS: The intrinsic cardiac
      nervous system receives reduced input from extracardiac sympathetic efferent
      neurons after transplantation and inconsistent input from parasympathetic
      efferent preganglionic neurons. These heterogeneous neuronal inputs are not
      reflected in heart rate variability or ventricular beta-adrenergic receptor
      function. Transplanted angiotensin II-sensitive intrinsic cardiac neurons exert
      greater cardiac control than do nicotine-sensitive ones. The intrinsic cardiac
      nervous system remodels itself after cardiac transplantation, and this indicates
      that direct assessment of extracardiac and intrinsic cardiac neuronal behavior is
      required to fully understand cardiac control after transplantation.

PMID- 10892923
TI  - Esophageal Doppler monitor determinations of cardiac output and preload during
      cardiac operations.
AB  - BACKGROUND: Perioperative management of cardiac surgical patients frequently
      mandates measurements of cardiac output and left ventricular filling. This study
      compared cardiac output and left ventricular filling measured by pulmonary artery
      (PA) catheter and esophageal Doppler monitor (EDM). METHODS: Thirty-four patients
      undergoing coronary artery bypass grafting were prepared by implanting a PA
      catheter, an EDM, and a transit-time ultrasonic flow probe around the ascending
      aorta. In 20 patients, left ventricular end-diastolic short-axis area (EDA) was
      measured by transesophageal echocardiography. At five time points, cardiac output
      was measured from the flow probe, the EDM, and the PA catheter (by
      thermodilution), and left ventricular filling was assessed from the PA catheter
      (as PA diastolic pressure), the EDM (corrected flow time), and the EDA. For
      cardiac output, concordance correlations relating EDM to flow probe and PA
      catheter to flow probe were calculated, transformed (Fisher's z transformation),
      and compared by Student's t test. For left ventricular filling, regression
      coefficients were created between corrected flow time and EDA and between PA
      diastolic pressure and EDA. Spearman correlations were compared by Wilcoxon rank
      sum test. RESULTS: The EDM and the PA catheter exhibited similar relationships to
      the flow probe (concordance correlations, 0.55 +/- 0.35 [mean +/- standard
      deviation] and 0.49 +/- 0.34, respectively; p = 0.088). The correlation between
      corrected flow time and EDA was better than the correlation between PA diastolic
      pressure and EDA (concordance correlations, 0.49 +/- 0.55 versus 0.10 +/- 0.43,
      respectively; p < 0.01). CONCLUSIONS: These data suggest that the EDM may offer a
      less invasive technique for evaluating cardiac output and a more accurate
      estimate for preload compared with the PA catheter.

PMID- 10892924
TI  - Minimally invasive coronary artery revascularization on the beating heart.
AB  - BACKGROUND: The quality of surgical beating heart revascularization is frequently
      questioned, especially when the surgical access is limited. Nevertheless, the
      number of off-pump coronary procedures is expanding worldwide. METHODS: Since
      getting started with minimally invasive direct coronary artery bypass to anterior
      myocardial vessels in June 1996, 306 patients received left internal mammary
      artery grafting through an anterior minithoracotomy. Risk increasing
      comorbidities were present in 168 of them. Particular attention was paid to early
      postoperative angiographic results and complications. RESULTS: The 30-day
      mortality summed up at 1.0% and was limited to patients with additional risks for
      conventional bypass grafting. Early postoperative control angiographies in 232
      patients confirmed a global patency rate of 97.8%, revealing in addition four
      unexpected malinsertions to diagonal branches. In surviving patients major
      complications like myocardial infarction, stroke, or multiorgan failure were
      completely absent. CONCLUSIONS: Minimally invasive direct coronary artery bypass
      grafting appears to allow for a safe and effective revascularization of the left
      anterior descending artery by use of the left internal mammary artery. Especially
      patients with risk increasing comorbidities should benefit from this approach,
      provided the surgical indication based on a dominating left anterior descending
      artery lesion. Angiographic minimally invasive direct coronary artery bypass
      results seem to fulfill the expectations generated by results obtained in
      conventional left internal mammary artery grafting and appear to be superior to
      interventional means.

PMID- 10892925
TI  - Coronary and carotid operations under prospective standardized conditions:
      incidence and outcome.
AB  - BACKGROUND: No randomized trial has yet evaluated the hypothetical benefit of
      carotid endarterectomy with coronary artery bypass grafting. This prospective
      review was undertaken to determine the differences between observed and predicted
      complication rates, as well as to define new predictors and assess costs in a
      standardized population. METHODS: A prospective nonrandomized study was
      undertaken over a 4-year period involving all coronary artery bypass graftings
      done at one institution. Operative procedure was standardized. All patients
      underwent preoperative screening for carotid disease. If 80% or more stenosis was
      present, combined coronary artery bypass grafting and carotid endarterectomy was
      performed. RESULTS: Of 2,071 patients, 1,987 had coronary artery bypass grafting
      only. In that group there were 34 strokes (1.7%) and 41 deaths (2.0%). Eighty
      four patients underwent combined coronary artery bypass grafting/carotid
      endarterectomy and in that group there were four strokes (4.7%) and five deaths
      (5.9%). Independent risk factors for postoperative stroke were age (odds ratio
      1.09; 95% confidence interval 1.04, 1.3), hypertension (odds ratio 2.67; 95%
      confidence interval 1.22, 5.23), extensively calcified aorta (odds ratio 2.82;
      95% confidence interval 1.34, 5.97), and bypass time (odds ratio 1.01; 95%
      confidence interval 1.00, 1.02). Cost of a stroke was significant (p < 0.05) in
      both groups. CONCLUSIONS: Patients with carotid disease fall into a higher risk
      group than patients without it. This increased risk is not because of carotid
      disease alone. Patients without significant carotid disease, who suffered a
      perioperative stroke, fell into an even higher risk category. Furthermore,
      carotid endarterectomy was not a significant risk factor by either the univariate
      or the multivariate analysis.

PMID- 10892926
TI  - Myocardial metabolism and efficiency after warm continuous blood cardioplegia.
AB  - BACKGROUND: Warm continuous blood cardioplegia (WCBCP) has been recommended
      during prolonged cardiac arrest to minimize functional deterioration. Myocardial
      metabolism and efficiency after this cardioplegic modality are not well
      described. METHODS: Substrate oxidation, blood flow, and myocardial function were
      measured before, during, and after 3 hours of WCBCP in 7 pigs. RESULTS: Free
      fatty acid and glucose oxidation decreased by 60% +/- 3.8% and 94% +/- 1.2%,
      respectively, during cardioplegia (both p < 0.05) and increased to 62% +/- 28%
      and 122% +/- 62% of baseline during the early recovery phase (p < 0.05 for
      glucose). One hour after WCBCP oxidation rates were similar to baseline. The
      transient postcardioplegic increase in substrate oxidation was associated with a
      43% +/- 23% elevation of oxygen consumption (MVO2) compared with baseline and a
      62% +/- 18% increase in myocardial blood flow. Cardiac output and mean arterial
      pressure did not change significantly after WCBCP, although myocardial function
      (stroke work, left ventricular end-systolic pressure, end-diastolic pressure,
      contractility, and efficiency) was depressed (p < 0.05). End-diastolic pressure
      and contractility improved from early to late phase of recovery, whereas the
      other indicators of ventricular function remained depressed. CONCLUSIONS:
      Myocardial substrate oxidation was preserved after 3 hours of WCBCP, although
      ventricular function was moderately impaired. Thus, WCBCP with a seemingly normal
      substrate and oxygen supply was associated with a reduced cardiac efficiency.

PMID- 10892927
TI  - Near-infrared monitoring of myocardial oxygenation during ischemic
      preconditioning.
AB  - BACKGROUND: Ischemic preconditioning has been advocated as a method of
      cardioprotection for minimally invasive direct coronary artery bypass. This study
      was performed to estimate the cardioprotective effect of ischemic preconditioning
      before ischemia by examining the changes in myocardial tissue oxygenation and
      also to examine whether adenosine triphosphate-sensitive potassium channel opener
      enhances the cardioprotective effect of ischemic preconditioning. METHODS:
      Myocardial ischemia was induced in three groups of 6 dogs by temporary occlusion
      of the left anterior descending coronary artery. Group 1 dogs received a 30
      minute coronary occlusion and subsequent 3-hour reperfusion. Groups 2 and 3 dogs
      underwent three periods of 5-minute coronary occlusion and 5-minute reperfusion
      and then received 30-minute sustained ischemia and 3-hour reperfusion. In group
      3, nicorandil was administered during the procedure. Myocardial oxygenation was
      measured using three-wavelength near-infrared spectroscopy. Myocardial blood flow
      was measured by the colored microsphere method. RESULTS: During ischemic
      preconditioning the myocardial tissue oxygen saturation decreased rapidly at
      coronary occlusion and increased at reperfusion. It was increased stepwise at the
      second and third coronary occlusion. Myocardial oxygen saturation during 30
      minute sustained ischemia was significantly higher in groups 2 and 3 than in
      group 1 (p < 0.05). The myocardial tissue hemoglobin concentration showed similar
      changes to myocardial oxygen saturation. During 30-minute sustained ischemia, it
      was significantly higher in group 2 than in group 1 (p < 0.001), and it was
      significantly higher in group 3 than in groups 1 and 2 (p < 0.05). Regional
      myocardial blood flow showed no difference after 30 minutes of sustained ischemia
      among the three groups. Troponin-T levels were significantly lower in groups 2
      and 3 than in group 1 (p < 0.01). CONCLUSIONS: Ischemic preconditioning had
      beneficial effects on myocardial oxygenation during sustained ischemia, and the
      protected state of the myocardium could be monitored with the use of near
      infrared spectroscopy. Ischemic preconditioning coupled with nicorandil
      administration might provide protection for minimally invasive direct coronary
      bypass.

PMID- 10892928
TI  - Excimer versus carbon dioxide transmyocardial laser revascularization: effects on
      regional left ventricular function and perfusion.
AB  - BACKGROUND: Transmyocardial laser revascularization (TMR) has been established
      with the carbon dioxide (CO2) laser. The largely unstudied excimer laser creates
      channels through chemical bond dissociation instead of thermal ablation, thereby
      avoiding thermal injury. We sought to compare the effects of CO2 and excimer TMR
      in a porcine model of chronic ischemia. METHODS: Pigs underwent ameroid
      constrictor placement on the circumflex artery to create chronic ischemia. TMR
      was performed with CO2 (n = 8) or excimer (n = 8) laser 6 weeks later; controls
      (n = 7) had ameroid placement only. Regional myocardial blood flow (RMBF),
      determined by radioactive microspheres, and regional myocardial function,
      determined by percent segmental shortening (%SS), were assessed 18 weeks after
      ameroid placement. RESULTS: Values are mean +/- SD. In the ischemic zone, RMBF
      (mL/min/g) was improved in the CO2 (0.73 +/- 0.19) and excimer (0.78 +/- 0.22)
      groups when compared with controls (0.55% +/- 0.12%, p < 0.05). %SS was also
      improved in the CO2 (15.2% +/- 5.5%) and excimer (15.3% +/- 5.1%) groups when
      compared with controls (8.0% +/- 4.2%, p < 0.05). CONCLUSIONS: Excimer and CO2
      TMR significantly improve RMBF and regional function in this porcine model of
      chronic myocardial ischemia despite fundamentally different tissue interactions.

PMID- 10892929
TI  - Collection of process data after cardiac surgery: initial implementation with a
      Java-based intranet applet.
AB  - BACKGROUND: Using a Java-based intranet program (applet), we collected
      postoperative process data after coronary artery bypass grafting. METHODS: A Java
      based applet was developed and deployed on a hospital intranet. Briefly, the
      nurse entered patient process data using a point and click interface. The applet
      generated a nursing note, and process data were saved in a Microsoft Access
      database. In 10 patients, this method was validated by comparison with a
      retrospective chart review. In 45 consecutive patients, weekly control charts
      were generated from the data. When aberrations from the pathway occurred,
      feedback was initiated to restore the goals of the critical pathway. RESULTS: The
      intranet process data collection method was verified by a manual chart review
      with 98% sensitivity. The control charts for time to extubation, intensive care
      unit stay, and hospital stay showed a deviation from critical pathway goals after
      the first 20 patients. Feedback modulation was associated with a return to
      critical pathway goals. CONCLUSIONS: Java-based applets are inexpensive and can
      collect accurate postoperative process data, identify critical pathway
      deviations, and allow timely feedback of process data.

PMID- 10892930
TI  - Milrinone for long-term pharmacologic support of the status 1 heart transplant
      candidates.
AB  - BACKGROUND: We determined the efficacy of long-term therapy with milrinone alone
      or in combination with inotropic agents in status 1 heart transplant candidates
      as a pharmacological support until heart transplantation. METHODS: Hemodynamic
      and biochemical variables were recorded in 29 status 1 men with symptoms of
      severe congestive heart failure, who received continuous intravenous milrinone
      alone (group 1, n = 21) or in combination with inotropic agents (group 2, n = 8)
      while awaiting heart transplantation. RESULTS: Symptomatic relief was noted in
      all patients of both groups without any preoperative deaths. One patient (4.8%)
      of group 1 died on the second day and 1 patient of group 2 died 16.4 months after
      transplantation. Although pulmonary capillary wedge pressure (group 1, p = 0.021;
      group 2, p = 0.0002), mean pulmonary artery pressure (group 1, p = 0.051; group
      2, p = 0.004), and pulmonary vascular resistance (group 1, p = 0.0026; group 2, p
      = 0.056) were reduced by 1 hour after the onset of treatment and maintained
      unchanged until transplantation, the changes in mean pulmonary artery pressure in
      group 1 and pulmonary vascular resistance in group 2 were statistically
      insignificant except in the posttransplantation period. CONCLUSIONS: Long-term
      therapy with milrinone in combination with inotropic agents is safe and effective
      when only milrinone infusion is inadequate for pharmacologic support in status 1
      candidates.

PMID- 10892931
TI  - Heparin-induced platelet dysfunction and cardiopulmonary bypass.
AB  - BACKGROUND: Cardiopulmonary bypass is associated with impaired platelet
      macroaggregation. Heparin contributes to platelet dysfunction before
      extracorporeal circulation. In vitro heparinization of whole blood does not
      impair macroaggregation. Heparin releases several endothelial proteins; thus
      heparin may inhibit macroaggregation indirectly. METHODS: Patients undergoing
      operations using cardiopulmonary bypass and ABO blood group compatible volunteers
      were studied. Whole blood impedance aggregometry assessed macroaggregation in
      response to collagen (0.6 microg ml(-1)) in blood diluted either with normal
      saline or with platelet poor plasma, obtained from patients at different stages
      of cardiopulmonary bypass. RESULTS: Before heparinization, blood diluted with its
      own platelet poor plasma recorded an impedance change of 13.0 (4.7 to 15.6) Ohms.
      Platelet poor plasma obtained after heparinization or during extracorporeal
      circulation reduced this response to 3.7 (1.1 to 8.4) and 2.0 (1.1 to 3.3) Ohms,
      respectively (both p < 0.0001 versus pre-heparin; n = 13). Macroaggregation in
      blood from volunteers was similarly inhibited by patients' platelet poor plasma
      (n = 30). The macroaggregatory response in blood sampled after heparinization for
      cardiopulmonary bypass, decreased gradually from 11.4 (8.2 to 15.9) Ohms
      immediately after sampling to 1.7 (1.4 to 4.1) Ohms 2 hours later (p < 0.0001; n
      = 11). CONCLUSIONS: In vivo heparinization induces plasma changes that inhibit
      platelet macroaggregation. This is an indirect, delayed inhibition that is
      transferable in vitro to normal platelets.

PMID- 10892932
TI  - The harmonic scalpel: optimizing the quality of mammary artery bypass grafts.
AB  - BACKGROUND: The damage done to the endothelium during the preparation of a graft
      used in an aortocoronary procedure is a risk factor for early graft failure. We
      compared the effect on the endothelium of the mammary arteries when the harvest
      was done either by the harmonic scalpel (HS) or the high-frequency electrocauter
      (HF). METHODS: Twenty-four mammary arteries were harvested and divided into two
      groups depending on the use of the HS or the HF. The endothelial damage was
      analyzed with a scanning electron microscope. The groups were compared in regard
      to the size of the internal mammary artery (IMA) pedicle. RESULTS: The
      endothelial damage of the IMAs taken down with the HS was significantly less than
      when taken down with the HF if the IMA pedicle size was less than 0.5 cm.
      CONCLUSIONS: The HS has a positive effect on the endothelial preservation,
      especially when the preparation is done closely to the IMA. The HS is profitable
      in minimally invasive procedures, particularly when it is difficult to keep a
      wide enough distance from the IMA.

PMID- 10892933
TI  - Partial left ventriculectomy: which patients can be expected to benefit?
AB  - BACKGROUND: Although some patients with end-stage heart disease will benefit from
      a partial left ventriculectomy, no criteria have been found for identifying this
      group preoperatively. Our experience with partial left ventriculectomy at two
      institutions-the Texas Heart Institute in Houston, TX, USA, and Dedinje
      Cardiovascular Institute in Belgrade, Yugoslavia-showed a higher survival rate
      and better postoperative myocardial function in the Yugoslavian patients.
      METHODS: We reviewed data from 42 patients (21 at each center) who had idiopathic
      cardiomyopathy, a left ventricular end-diastolic dimension of more than 70 mm,
      wall thickness of 1 cm or greater, and New York Heart Association class III or IV
      symptoms. The only significant difference in preoperative status between the two
      groups was duration of symptoms. Histologic specimens, blinded as to origin, were
      graded with regard to myocyte hypertrophy, cytoplasmic vacuolation, and fibrosis.
      Computer-assisted myocyte and nuclear morphometry was also performed. RESULTS:
      Immediately postoperatively, there were no significant intergroup differences in
      the reduction in cardiac dimension or in corrections of mitral regurgitation.
      During 6-month follow-up, however, the Texas Heart Institute patients had a lower
      cardiac index (1.8 versus 3.0 L x min(-1) x m(-2); p = 0.001) and left
      ventricular ejection fraction (24% versus 34%; p = 0.006) than the Dedinje
      Cardiovascular Institute patients. The Texas Heart Institute patients differed
      from the Dedinje Cardiovascular Institute patients in the degree of severe or
      moderate changes in myocyte hypertrophy (90% versus 29%; p = 0.0003) and fibrosis
      (71% versus 29%; p = 0.006), as well as in the measurements of median myocyte
      diameter (35 +/- 7 microm versus 27 +/- 4 microm; p = 0.0002) and median nuclear
      size (15 +/- 4 microm versus 12 +/- 2 microm; p = 0.0029). CONCLUSIONS: In the
      Texas Heart Institute patients, the significant intergroup difference in clinical
      outcome may have been related to increased myocyte hypertrophy and fibrosis.
      Further studies should be performed to determine the usefulness of these criteria
      in selecting patients for partial left ventriculectomy.

PMID- 10892934
TI  - Optimizing timing of early extubation in coronary artery bypass surgery patients.
AB  - BACKGROUND: This study was designed to assess the safety and efficacy of
      extubation performed within 4 hours of the patient's arrival in the surgical
      intensive care unit after coronary artery bypass graft surgery. METHODS: A
      matched retrospective cohort study was performed including 412 consecutive
      patients undergoing isolated coronary artery bypass graft surgery between January
      1996 and December 1997, constituting the experience of a single surgeon (J.H.L.).
      Early extubation (defined as extubation within 8 hours of arrival at the surgical
      intensive care unit) was achieved in 308 of 412 patients (75%). Patients
      extubated in fewer than 4 hours after arrival (n = 200) were compared with
      patients extubated within 4 to 8 hours (n = 108). RESULTS: Four deaths occurred
      in 412 patients, for an overall operative mortality rate of 1.0%. Patients
      extubated in fewer than 4 hours were younger than those extubated 4 or more hours
      after admission (62 versus 67 years old, respectively; p = 0.001), more likely to
      be male (74% versus 63%, p < 0.05), and had shorter aortic cross-clamp times
      (49.4 +/- 15.0 versus 53.5 +/- 14.0 minutes, p < 0.05) and cardiopulmonary bypass
      (CPB) times (65.2 +/- 18.6 versus 72.1 +/- 19.1 minutes, p < 0.05) compared to
      patients extubated later. Moreover, patients extubated in fewer than 4 hours had
      a shorter surgical intensive care unit length of stay (33.8 +/- 25.7 versus 43.1
      +/- 43.0 hours, p < 0.05) and shorter postoperative length of stay (5.4 +/- 2.4
      versus 6.2 +/- 2.6 days, p = 0.01) than those extubated later. CONCLUSIONS:
      Extubation in fewer than 4 hours may offer a substantial advantage in terms of
      accelerated recovery compared with extubation within 4 to 8 hours. Very few
      differences in clinical parameters were noted between the two groups we studied,
      suggesting that efforts to reduce extubation times further might be worthwhile.

PMID- 10892935
TI  - Early experience with the mosaic bioprosthesis: a new generation porcine valve.
AB  - BACKGROUND: The Mosaic bioprosthesis is a new generation stented porcine valve.
      METHODS: Between May 1995 and April 1998, this valve was implanted in the aortic
      position in 98 patients (70 men; mean age, 69.2 years [34.2 to 83.6 years]).
      Preoperatively 35 patients were in New York Heart Association functional class 3
      or 4. Fifty-nine patients underwent concomitant procedures. The mean duration at
      follow-up in January 1999 was 23.7 +/- 10.2 months (0.3 to 39.4 months) and
      totaled 193 patient-years. All but one survivor was in New York Heart Association
      class 1 or 2. RESULTS: Early complications included 1 death, 3 reoperations for
      bleeding, greater than mild regurgitation (paravalvar) in 1 patient and
      thromboembolism in 4 patients. Late complications included four deaths, study
      valve endocarditis in 3 patients, more than mild regurgitation or hemolysis in 2,
      and thromboembolism in 2 patients. Late follow-up echocardiography in all
      survivors showed a mean transaortic gradient of 13.6 +/- 6.7 mm Hg, and an aortic
      valve area of 1.80 +/- 0.61 cm2. Valve replacement was followed by a significant
      and sustained decrease in left ventricular mass for all valve sizes. There has
      been no primary structural valve failure. CONCLUSIONS: The early experience with
      the Mosaic valve in the aortic position has been promising.

PMID- 10892936
TI  - Mechanisms of aortic valve incompetence: finite element modeling of aortic root
      dilatation.
AB  - BACKGROUND: Idiopathic root dilatation often results in dysfunction of an
      otherwise normal aortic valve. To examine the effect of root dilatation on
      leaflet stress, strain, and coaptation, we utilized a finite element model.
      METHODS: The normal model incorporated the geometry, tissue thickness, stiffness,
      and collagen fiber alignment of normal human roots and valves. We evaluated four
      dilatation models in which diameters of the aortic root were dilated by 5%, 15%,
      30%, and 50%. Regional stress and strain were evaluated and leaflet coaptation
      percent was calculated under diastolic pressure. RESULTS: Root dilatation
      significantly increased regional leaflet stress and strain beyond that found in
      the normal model. Stress increases ranged from 57% to 399% and strain increases
      ranged from 39% to 189% in the 50% dilatation model. Leaflet stress and strain
      were disproportionately high at the attachment edge and coaptation area. Leaflet
      coaptation was decreased by 18% in the 50% root dilatation model. CONCLUSIONS:
      Idiopathic root dilatation significantly increases leaflet stress and strain and
      reduces coaptation in an otherwise normal aortic valve. These alterations may
      affect valve-sparing aortic root replacement procedures.

PMID- 10892937
TI  - Right ventricle-sparing heart transplant: promising new technique for recipients
      with pulmonary hypertension.
AB  - BACKGROUND: Right heart failure remains the leading early cause of mortality
      after heart transplantation, especially with antecedent pulmonary hypertension.
      Paradoxically, the discarded recipient right heart, acclimated to pulmonary
      hypertension, is often stronger than its nonconditioned donor replacement.
      Heterotopic ("piggyback") transplantation is plagued by problems related to the
      retained, dilated, hypocontractile left ventricle (lung compression, systemic
      emboli, arrhythmias). Were it possible to retain the recipient's right heart,
      excising only the left ventricle, this could have important advantages,
      especially in severe pulmonary hypertension. This report describes such a
      technique. METHODS AND RESULTS: In four transplantation experiments (dogs), right
      ventricular-sparing transplantation proved technically feasible and
      hemodynamically successful. Bleeding after excision of the left ventricle was
      easily controlled. Back-bleeding from the native aortic valve (now open into the
      pericardial space) was not problematic. All atrial, aortic, and pulmonary
      arterial connections proved feasible. The preserved recipient right heart of all
      animals remained in stable sinus rhythm. All recipients were easily weaned from
      cardiopulmonary bypass, maintaining mean arterial pressures 60 to 110 mm Hg.
      CONCLUSIONS: This investigation develops a technique for donor right ventricle
      sparing in cardiac transplantation, demonstrating technical and hemodynamic
      feasibility. This method holds promise for the unsolved clinical problem of right
      heart failure after orthotopic heart transplantation with antecedent pulmonary
      hypertension.

PMID- 10892938
TI  - Incidence and size of lateral costal artery in 103 patients.
AB  - BACKGROUND: The internal mammary artery is used widely as a conduit for coronary
      artery bypass grafting. Most practicing cardiac surgeons are unaware of an
      aberrant side branch, the lateral costal artery (LCA), that arises proximally.
      Unligated, this side branch has been held responsible for early recurrence of
      angina in a small number of patients in the literature. In this study we
      identified the incidence and length of the LCA. METHODS: We studied 103 patients
      who had coronary artery bypass grafting with bilateral internal mammary arteries.
      The presence or absence of an LCA was noted, and a record was made of the number
      of intercostal spaces traversed. RESULTS: Thirty-one of 103 patients had an LCA
      on one or the other side. Twenty-five patients had bilateral LCAs in which length
      was equal on both sides in 18. Median length was two intercostal spaces (range,
      one to six). The LCA extended to the fifth space or beyond in 5 patients.
      CONCLUSIONS: The LCA was present in one third of patients who had coronary artery
      bypass grafting. A few patients had vessels sizable enough to raise concerns
      about recurrence of angina. It is prudent to exclude the presence of an LCA in
      all patients who have cardiac operations.

PMID- 10892939
TI  - Immunochemical analysis of polyspecific antibodies in patients exposed to bovine
      fibrin sealant.
AB  - BACKGROUND: Patients exposed to bovine thrombin preparations in fibrin sealant
      often develop antibodies to bovine coagulation proteins, which cause significant
      bleeding by cross-reacting with human homologues. Recipients of our left
      ventricular assist system (LVAS) routinely are exposed to fibrin sealant;
      therefore, we determined whether they developed antibodies. METHODS: We compared
      sera from 6 LVAS recipients exposed to fibrin sealant (THROMBOGEN, Johnson &
      Johnson, Arlington, TX ) during LVAS placement to that of 5 nonexposed LVAS
      recipients. Pre-LVAS and weekly post-LVAS sera were tested for immunoglobulin
      (Ig)G, IgA, and IgM reactivity to THROMBOGEN by enzyme-linked immunosorbent
      assay. Peak IgG and IgA reactive sera were characterized by immunoblotting.
      RESULTS: All patients exposed to THROMBOGEN developed antibodies: 5 developed
      IgG, 4 IgA, and 3 IgM. In contrast, nonexposed patients did not develop
      antibodies. Only some antibody reactivity was contributed by antithrombin or
      antifactor V antibodies. Silver stain sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analyses of THROMBOGEN showed more than 18 bands, many of which
      were recognized in Western blot by positive patient sera. CONCLUSIONS: We found
      both IgG and IgA polyspecific antibody responses in patients exposed to bovine
      thrombin preparations.

PMID- 10892940
TI  - Evolution of the Fontan procedure in a single center.
AB  - BACKGROUND: Surgical approaches to single ventricle variants include staged,
      fenestrated, and completed Fontan operations. This study compares outcomes with
      these modifications of the Fontan operation at a single center. METHODS:
      Preoperative risk factors and operative results were analyzed by multivariate
      techniques in 129 patients undergoing modified Fontan operations since March
      1988. RESULTS: Overall early and late mortality was 5.4% and 0.8%, respectively.
      Before 1993, completed Fontan operation using right atrial to pulmonary artery
      anastomosis without fenestration was performed in the majority of patients (44 of
      58; 76%). During this period, 10 of 17 patients at high risk had completed Fontan
      with three takedowns. In 1994, the staged hemi-Fontan and modified Fontan with a
      lateral tunnel anastomosis and with or without small fenestration (2.5 to 4 mm)
      were introduced. The majority of patients at high risk during this period
      underwent hemi-Fontan followed by fenestrated Fontan with no takedowns. Late
      atrial dysrhythmias occurred in 6 patients (4.7%), generally with larger
      fenestrations or right atrial to pulmonary anastomoses. Three patients (2.3%) had
      a stroke, 2 with large (> or = 4 mm) fenestrations. Of 38 fenestrations, 32 (84%)
      closed spontaneously by 1 year. No protein-losing enteropathy occurred. Most
      patients (118 of 121) were in New York Heart Association class I/II 4.5 years
      postoperatively. By multivariate analysis, only Down's syndrome (p < 0.001)
      predicted early mortality, whereas both Down's syndrome and a systemic right
      ventricle decreased late survival (p < 0.006). CONCLUSIONS: Proper selection of
      patients for modifications of the Fontan procedure resulted in excellent early
      and late survival with a low incidence of atrial dysrhythmia and stroke. Midterm
      functional outcomes were excellent.

PMID- 10892942
TI  - Modified arterial switch operation by spiral reconstruction of the great arteries
      in transposition.
AB  - BACKGROUND: Spiral relationship of the normally related great arteries (SRGA) has
      never been reconstructed in an arterial switch operation. METHODS: From March
      1998 to April 1999, 9 consecutive cases of transposition of the great arteries
      (TGA) family (from 2 days to 1.6 years old) underwent arterial switch operations
      with SRGA at our hospital. Two had a congenitally corrected TGA (plus atrial
      redirection). Lecompte maneuver was not used in all. The posterior wall of
      pulmonary trunk was not divided but three were reattached, two of whom had had
      previous pulmonary trunk banding. Thus the wall was shared between the great
      arteries facing each other. RESULTS: All survived the operation. Supraaortic
      stenosis was balloon-dilated in 2 cases of early series, but technical
      modifications later were able to avoid it. Angiogram showed smooth flow into SRGA
      without upward and anterior tilting of the pulmonary bifurcation. All great and
      coronary arteries were patent. All were doing well on follow-up (16.5 +/- 4.2
      months). CONCLUSIONS: We concluded that the techniques to relocate the coronary
      arteries using common wall and in situ switch could also be applied to pulmonary
      arterial reconstruction, so that SRGA can be resumed in TGA.

PMID- 10892941
TI  - Anatomical risk factors for mortality and cardiac morbidity after arterial switch
      operation.
AB  - BACKGROUND: The arterial switch operation (ASO) is the treatment of choice for
      transposition of the great arteries. METHODS: Anatomical risk factors on
      mortality and morbidity were analyzed retrospectively in 312 patients who
      underwent ASO between 1982 and 1997. RESULTS: Survival was 95%, 92%, and 92%
      after 30 days, 5, and 10 years, respectively. Operative survival improved after
      1990 to 97% (p < 0.001). Risk factors for operative mortality were complex
      anatomy (p = 0.018), coronary anomalies (p = 0.008), and prolonged bypass time (p
      < 0.001). Determinants of late mortality were coronary distribution (p = 0.03),
      position of the great arteries (p = 0.0095), bypass time (p = 0.047), and aortic
      coarctation (p = 0.046). After a follow-up of 3.6 +/- 2.7 years (0.1 to 14.9
      years), 98% had good left ventricle function, 94% were in sinus rhythm, 2.4% had
      moderate to severe pulmonary stenosis, 0.3% had significant aortic regurgitation,
      and 1% had coronary stenosis. Freedom from reoperation was 100%, 96%, and 94%
      after 1, 5, and 10 years, respectively. No preoperative anatomic parameter
      correlated with long-term morbidity. CONCLUSIONS: ASO can be performed with low
      operative mortality (< 5%) and long-term morbidity. Malformations associated with
      complex transposition of the great arteries influence early and late mortality.

PMID- 10892943
TI  - Patients at risk for low systemic oxygen delivery after the Norwood procedure.
AB  - BACKGROUND: Identification of patients at risk for inadequate systemic oxygen
      delivery following the Norwood procedure could allow for application of more
      intensive monitoring, provide for earlier intervention of decreased cardiac
      output, and result in improved outcome. METHODS AND RESULTS: Superior vena cava
      saturation (SvO2) and arteriovenous oxygen content difference were prospectively
      monitored as indicators of systemic oxygen delivery and recorded hourly for the
      first 48 hours in 29 of 33 consecutive patients following the Norwood procedure.
      Risk factors were evaluated using multiple linear regression to determine their
      impact on SvO2 and arteriovenous oxygen content difference. Age less than 8 days,
      weight less than 2.5 kg, aortic atresia, and prolonged cardiopulmonary bypass
      time were risk factors for low SvO2 and wide arteriovenous oxygen content
      difference (p < 0.05). Phenoxybenzamine and increasing time after operation were
      associated with higher SvO2 and narrower arteriovenous oxygen content difference
      (p < 0.05). Thirty-day survival was 97% and hospital survival was 94%. The
      earliest death occurred on postoperative day 20. Survival to bidirectional
      cavopulmonary shunt was 77%. Preoperative mechanical ventilation was the only
      risk factor identified for late death. CONCLUSIONS: Aortic atresia, low weight,
      younger age, and prolonged cardiopulmonary bypass, previously identified risk
      factors for mortality, were associated with decreased SvO2 and narrower
      arteriovenous oxygen content difference in the early postoperative period. The
      impact of this hemodynamic vulnerability on mortality was minimized by continuous
      SvO2 monitoring.

PMID- 10892944
TI  - Univentricular repair: is routine fenestration justified?
AB  - BACKGROUND: A decade after the introduction of baffle fenestration, the outcome
      of Fontan-type repair for hearts with a functional single ventricle finally looks
      promising. Our study was designed to assess the impact of fenestration on the
      outcome of univentricular repairs. METHODS: From January 1988 to December 1997,
      348 patients (104 with tricuspid atresia and 244 with other morphological
      diagnoses) underwent univentricular repair at our institute. Since 1994, routine
      fenestration of the atrial baffle was performed in all patients (n = 126).
      RESULTS: The overall Fontan failure rate was 14% (50 of 348) and included 45
      early deaths and five Fontan take downs. Absence of fenestration was the only and
      highly significant predictor of Fontan failure (risk ratio [RR] 3.3, 95%
      confidence interval [CI] 1.49 to 7.31, p = 0.002). Significant pleural effusion
      was seen in 27% of patients. Absence of fenestration of the atrial baffle (RR
      3.97, 95% CI 2.17 to 7.26, p < 0.001) and aortic cross-clamp time more than 60
      minutes (RR 2.15, 95% CI 1.3 to 3.5, p = 0.002) were found to be significant risk
      factors. The follow-up ranged from 6 to 120 months (mean 46.0 +/- 18.0 months).
      There were 12 late deaths and 5 patients were lost to follow-up. Actuarial
      survival (Kaplan Meier) at 90 months was 81% +/- 4%. Two hundred and fifty-eight
      patients (90%) were in New York Heart Association class I at their last follow-up
      visit. Oxygen saturation in the fenestrated group ranged from 85% to 94% (mean
      89%). Thirty patients (26%) had spontaneous closure of the fenestration over a
      mean period of 34 months, and there has been no incidence of late systemic
      thromboembolism. In no instance has there been a need to close the fenestration.
      CONCLUSIONS: Elective fenestration of the intraatrial baffle is associated with
      decreased Fontan failure rate and decreased occurrence of significant
      postoperative pleural effusions. Routine elective fenestration of the atrial
      baffle may, therefore, be justified in all univentricular repairs.

PMID- 10892945
TI  - Randomized controlled study of inhaled nitric oxide after operation for
      congenital heart disease.
AB  - BACKGROUND: Inhaled nitric oxide selectively decreases pulmonary vascular
      resistance. This study was performed to determine whether inhaled nitric oxide
      decreases the incidence of pulmonary hypertensive crises after corrective
      procedures for congenital heart disease. METHODS: Patients with a systolic
      pulmonary arterial pressure of 50% or more of the systolic systemic arterial
      pressure during the early postoperative period were randomized to receive 20
      parts per million inhaled nitric oxide (n = 20) or conventional therapy alone (n
      = 20). Acute hemodynamic and blood gas measurements were performed at the onset
      of therapy. The efficacy of sustained therapy was determined by comparing the
      number of patients in each group who experienced a pulmonary hypertensive crisis.
      RESULTS: In comparison to controls, there were no significant differences in the
      baseline and 1-hour measurements of patients who were treated with nitric oxide.
      Four patients in the control group and 3 patients in the nitric oxide group
      experienced a pulmonary hypertensive crisis. CONCLUSIONS: Nitric oxide did not
      substantially improve pulmonary hemodynamics and gas exchange immediately after
      operation for congenital heart disease. Nitric oxide also failed to significantly
      decrease the incidence of pulmonary hypertensive crises.

PMID- 10892946
TI  - Clinical evaluation of leukocyte-depleted blood cardioplegia for pediatric open
      heart operation.
AB  - BACKGROUND: Blood cardioplegia (BCP) is widely used for myocardial protection
      during open heart operation. However, BCP may have a chance to induce neutrophil
      mediated myocardial injury during aortic cross-clamping. We clinically evaluated
      the myocardial protective effect of leukocyte-depleted blood cardioplegia (LDBCP)
      for initial and intermittent BCP administration in pediatric patients. METHODS:
      Fifty patients undergoing open heart operation for congenital heart disease
      between January 1997 and March 1999 were reviewed. Twenty-five were administered
      LDBCP for myocardial protection during ischemic periods (LDBCP group), and the
      remaining 25 were given BCP without leukocyte depletion (BCP group). RESULTS: The
      difference in plasma concentrations of malondialdehyde between coronary sinus
      effluent blood and arterial blood just after reperfusion in the LDBCP group (1.68
      +/- 0.56 micromol/L) was significantly lower than that in the BCP group (2.35 +/-
      0.62 micromol/L; p < 0.01). The LDBCP group showed significantly lower plasma
      concentrations of human heart fatty acid-binding protein at 50 minutes after
      reperfusion (LDBCP group, 103.5 +/- 38.7 IU/L; BCP group, 144.8 +/- 48.8 IU/L; p
      < 0.01) and the peak value of creatine kinase-MB during the first 24
      postoperative hours (LDBCP group, 17.0 +/- 8.5 IU/L; BCP group, 26.0 +/- 11.6
      IU/L; p < 0.01) than did the BCP group. The maximum dose of catecholamine was
      significantly smaller in the LDBCP group (LDBCP group, 3.20 +/- 2.18 microg x kg(
      1) x min(-1); BCP group, 5.60 +/- 2.83 microg x kg(-1) x min(-1); p < 0.01).
      CONCLUSIONS: These results suggest the usefulness of LDBCP for protection from
      the myocardial injury that can be induced by BCP administration during aortic
      cross-clamping.

PMID- 10892947
TI  - Hemashield implantation in young patients with congenital cardiovascular lesions.
AB  - BACKGROUND: There is substantial controversy regarding the use of Hemashield in
      young patients. METHODS: Twenty-one consecutive patients younger than 20 years of
      age with a variety of congenital cardiovascular lesions underwent surgical
      procedures using a Hemashield woven graft. Hemashield was used for reconstruction
      of the aortic wall (n = 16), ventricular septum (n = 10), and right ventricular
      free wall or pulmonary artery (n = 6). RESULTS: A sterile inflammatory reaction
      was observed including high fever, increased white cell count, and elevated
      plasma C-reactive protein concentration for up to 4 weeks after implantation.
      Multivariable analysis identified the use of Hemashield in the right ventricular
      free wall or pulmonary artery as an incremental risk factor for elevation of
      plasma C-reactive protein concentration during the first 3 weeks after
      implantation (p = 0.002). There were no midterm complications including
      restenosis of the grafts in the right ventricular outflow tract. CONCLUSIONS:
      Hemashield can be used in a variety of situations for reconstruction of
      congenital cardiovascular lesions in young patients. Impregnated collagen can
      cause a significant systemic inflammatory reaction for several weeks after
      implantation, especially when used in the low-pressure right heart.

PMID- 10892948
TI  - Pericardial mesothelioma: the diagnostic dilemma of misleading images.
AB  - A young man with a short history of increasing dyspnea, cough, and ascites was
      initially diagnosed as having idiopathic constrictive pericarditis and referred
      for an operation. The procedure revealed an atypical invasive encapsulating
      disease. Complete resection was impossible, and only partial relief of
      constriction was achieved. The patient died shortly after. Histology revealed
      primary mesothelioma of the pericardium. The case illustrates the difficulty in
      establishing this diagnosis by echocardiography and computed tomography.

PMID- 10892949
TI  - Angioleiomyoma of the diaphragm.
AB  - We report a case of a large symptomatic angioleiomyoma of the diaphragm. The
      tumor was diagnosed by computed tomography and videothoracoscopic biopsy. We
      removed the tumor through a left thoracolaparotomy. Three months later, a local
      recurrence was removed through an upper midline laparotomy. The patient remains
      without evidence of a recurrence 48 months after the second operation.

PMID- 10892950
TI  - A continuous murmur after surgery for dissecting ascending aortic aneurysm.
AB  - We report a case of a subcutaneous arteriovenous fistula that developed after
      aortic surgery. A careful physical examination and the selective use of imaging
      tests can differentiate this relatively benign complication from the more serious
      causes of a continuous murmur in this setting.

PMID- 10892951
TI  - Aortic dissection in a weight lifter with nodular fasciitis of the aorta.
AB  - We report a case of spontaneous aortic dissection in a young weight lifter
      without aortic medial disease but with a myofibroblastic proliferation of the
      aortic adventitia consistent with nodular fasciitis. Successful treatment
      included ascending aorta replacement with Dacron graft and aortic valve
      resuspension. We believe that the underlying aortic pathology most likely
      contributed to the development of the aortic dissection.

PMID- 10892952
TI  - Third-degree burns due to intraoperative use of a Bair Hugger warming device.
AB  - We report the case of a 3-year-old boy who underwent correction of transposition
      of the great arteries who developed burns from use of a patient warming device.
      His repair had been delayed because he was from a developing country, and he was
      offered surgery as part of a humanitarian effort. Postoperatively he was noted to
      have second- and third-degree burns from use of a Bair Hugger (Augustine Medical,
      Eden Prairie, MN) warming system after cardiopulmonary bypass.

PMID- 10892953
TI  - Critical subaortic stenosis in a newborn caused by accessory mitral valve tissue.
AB  - A 2-week-old newborn girl underwent successful surgery in our clinic for critical
      subaortic stenosis caused by accessory mitral valve tissue, which, because of
      excessive growth, protruded into the left ventricular outflow tract. The
      preoperative pressure gradient below the aortic valve was 80 mm Hg. The operation
      consisted of resection of the accessory tissue through a combined aortotomy and
      atriotomy approach without residual pressure gradient and mitral valve
      incompetence. This approach is recommended to ensure that accessory tissue is
      removed without damaging the mitral valve.

PMID- 10892954
TI  - Pneumoperitoneum secondary to endoscopic harvest of saphenous vein graft.
AB  - Endoscopic harvest of saphenous vein graft for coronary artery bypass grafting
      decreases leg wound complications compared with traditional longitudinal
      incision. A case of pneumoperitoneum secondary to endoscopic harvest of saphenous
      vein using insufflation of carbon dioxide is reported. Hypercarbia, increased
      peak airway pressure, but no significant changes of hemodynamics, or myocardial
      ischemia were noted. The management of this rare complication is described.

PMID- 10892955
TI  - Dystrophic calcification of the radial artery.
AB  - The radial artery continues to enjoy resurgence in popularity as a conduit for
      coronary artery bypass grafting but few studies have examined the prevalence of
      preexisting disease in this vessel. We highlight a potential, avoidable pitfall
      when use of the radial artery for coronary artery bypass grafting is proposed.

PMID- 10892956
TI  - Acute type A aortic dissection: retrograde perfusion with left superior vena
      cava.
AB  - Retrograde cerebral perfusion with hypothermic circulatory arrest confers
      additional cerebral protection during repair of type A aortic dissection. We
      present a 42-year-old man with acute type A aortic dissection and a persistent,
      left superior vena cava. Cannulation of the right and left superior vena cava is
      used for retrograde perfusion of both hemispheres with bilateral monitoring of
      electroencephalogram and somatosensory-evoked potentials during and after the
      hypothermic circulatory arrest interval.

PMID- 10892957
TI  - Use of recombinant-hirudin in pulmonary thromboendarterectomy.
AB  - A patient with chronic thromboembolic pulmonary hypertension and heparin-induced
      thrombocytopenia successfully underwent pulmonary thromboendarterectomy with
      circulatory arrest, using recombinant hirudin as an alternative anticoagulant to
      heparin. Techniques for administration as well as monitoring of this drug's
      effects are discussed.

PMID- 10892958
TI  - Conservative management of postoperative chylothorax using somatostatin.
AB  - Chylothorax is a rare but serious postoperative complication of thoracic surgical
      procedures. We report the case of a 77-year-old man who underwent a coronary
      artery bypass procedure using a left internal mammary artery pedicle graft. A
      permanent pacemaker was required postoperatively. A persistent postoperative
      chylothorax developed necessitating continuous drainage and conservative
      management. Somatostatin was instituted when after 1 week this management failed
      to resolve the chylothorax. This led to rapid cessation of chyle production.
      Enteral feeding was reinstituted without complication and surgical intervention
      was avoided.

PMID- 10892959
TI  - Staged repair of acute type I aortic dissection and coarctation in pregnancy.
AB  - A 29-year-old gravid female presented at 22 weeks gestation with an acute Type I
      aortic dissection and coarctation of the aorta. She underwent emergent repair of
      her aortic dissection using cardiopulmonary bypass and hypothermia. At 25 weeks
      gestation, she underwent repair of her coarctation of the aorta. The patient had
      a cesarean delivery of a viable, normal male infant at 39 weeks gestation.

PMID- 10892960
TI  - Esophageal schwannoma.
AB  - A rare case of esophageal schwannoma is presented. A 63-year-old woman was
      admitted to our hospital with a 5-year history of dysphagia. The barium
      esophagogram showed a protrusive smooth tumor in the upper thoracic esophagus.
      The tumor was removed through right thoracotomy. There was no anatomical
      relationship between the tumor and vagal nerve trunk. From pathologic findings
      and positive immunohistochemical staining for S-100 protein, the diagnosis of
      esophageal schwannoma was made.

PMID- 10892961
TI  - Primary right atrial synovial sarcoma manifesting as transient ischemic attacks.
AB  - Primary tumors of the heart are rare and most of them benign. The majority of
      benign cardiac tumors are myxomas while almost all malignant cardiac tumors are
      sarcomas. We present a case of primary right atrial synovial sarcoma, a form of
      sarcoma particularly rare in the heart. The tumor manifested clinically as
      transient ischemic attacks probably related to a patent foramen ovale allowing
      paradoxical tumor embolization.

PMID- 10892962
TI  - Midline exposure of the thoracoabdominal aorta.
AB  - Extended aortic replacement from the aortic arch to the descending thoracic or
      thoracoabdominal aorta has been performed through a left thoracotomy or a
      thoracoabdominal incision combined with or without a median sternotomy. However,
      a left thoracotomy incision may be unfavorable when dense adhesion of the lung is
      anticipated. We report a redo patient who underwent simultaneous replacements of
      the aortic arch and the thoracoabdominal aorta through a midline incision without
      entering the left pleural cavity.

PMID- 10892963
TI  - Intrathoracic migration of Kirschner pins.
AB  - We report two cases of intrathoracic migration of Kirschner pins used for the
      treatment of sternoclavicular joint dislocation. The migration was asymptomatic
      in both cases. Treatment involved median sternotomy in one patient and video
      assisted thoracoscopy in the other. A favorable outcome was observed in both
      patients. The reports confirm the potential dangers related to management of
      sternoclavicular joint dislocation with metallic fixation devices.

PMID- 10892964
TI  - Images in cardiothoracic surgery. Thrombus formation after catheter closure of an
      atrial septal defect with a clamshell device.

PMID- 10892965
TI  - Reinforcing the conventional sternal closure.
AB  - Sternal infection is a devastating complication of heart surgery. It may be the
      result of unstable osteosynthesis, caused by the sternal wires cutting into the
      cortical layers, which results in tension loss and gap formation. We describe a
      technique that prevents the cerclages from cutting into the sternal plates and
      covers the sternum with a well-capillarized barrier of major pectoralis muscle.

PMID- 10892966
TI  - Pericardial hood repair of cardiac rupture secondary to extended myocardial
      infarction.
AB  - A surgical technique for simple and safe repair of oozing-type postinfarction
      cardiac rupture secondary to extended myocardial infarction is described. A hood
      shaped pericardium was glued with gelatin-resorcinol and formaldehyde glue to
      cover the extended oozing infarcted myocardium. This technique was used on 3
      elderly patients with good results.

PMID- 10892967
TI  - The modified "hemi-clamshell" approach for tumors of the cervicothoracic
      junction.
AB  - The anterior approaches proposed for treatment of the apical chest tumors
      (anterior transcervical, transmanubrial, and hemi-clamshell) have precise
      advantages and limits. To avoid these limits we have modified the hemi-clamshell
      with the resection of the first costal cartilage and the costoclavicular
      ligament. This allows a wider opening of the sternocostal flap, with safe control
      of the entire subclavian vessels as well as easier access to the T1 to T3
      vertebral bodies and the posterior chest wall.

PMID- 10892968
TI  - Simple method for direct cannulation of ascending aortic aneurysms.
AB  - A simple method for direct cannulation of aneurysms of the ascending aorta is
      described. It avoids the need for femoral artery cannulation and offers an easy
      route for retrograde cerebral perfusion during deep hypothermic circulatory
      arrest.

PMID- 10892969
TI  - Robert H. Goetz: the surgeon who performed the first successful clinical coronary
      artery bypass operation.
AB  - Robert H. Goetz performed the first successful clinical coronary artery bypass
      operation on May 2, 1960. He used a nonsuture technique to connect the right
      internal thoracic artery to the coronary artery by means of a modified Payr's
      cannula made of tantalum. The patency of the anastomosis was demonstrated
      angiographically and the patient remained free of angina pectoris for 1 year. It
      was an important and brave step forward, a step that was far ahead of its time.
      Unfortunately, his pioneering work was not appreciated and fell into oblivion.

PMID- 10892970
TI  - Traumatic coronary artery fistula management.
AB  - Traumatic coronary artery-cameral fistulas (TCAF) are uncommon sequelae of trauma
      that require early surgical intervention to prevent complications. The etiology
      of traumatic coronary artery-cameral fistulas may be classified as accidental or
      iatrogenic and have distinctly different courses depending on the etiology. The
      two operations described for definitive surgical closure of a traumatic coronary
      cameral fistula are external ligation/obliteration of the fistula (with or
      without bypass grafting to the coronary artery distal to the fistula) and direct
      repair of the fistula from within the recipient chamber. The technique of fistula
      closure from within the recipient chamber is associated with a reduced incidence
      of fistula recurrence. A case report and a collective literature review are
      presented.

PMID- 10892971
TI  - Harvey's experiment on occlusion of the vena cava.

PMID- 10892972
TI  - Patient-prosthesis mismatch is not negligible.

PMID- 10892973
TI  - Ameroid constrictor versus hydraulic occluder: creation of hibernating
      myocardium.

PMID- 10892974
TI  - Endobronchial infiltration of malignant lymphoma.

PMID- 10892975
TI  - Impact of graft ischemic time on outcomes after lung transplantation.

PMID- 10892976
TI  - Endothelial function of bypass grafts: role of endothelin and
      tetrahydrobiopterin.

PMID- 10892977
TI  - Retrograde venous perfusion for spinal cord protection.

PMID- 10892978
TI  - Comparison between stentless xenografts and homografts.

PMID- 10892980
TI  - Thoracoscopic surgery, video-thoracoscopic surgery, or VATS: a confusion in
      definition.

PMID- 10892979
TI  - Tricuspid valve is bicuspid.

PMID- 10892981
TI  - A simple method to save on costs in pulmonary emphysema operations.

PMID- 10892982
TI  - Neurologic complications in coronary surgery without cardiopulmonary bypass.

PMID- 10892983
TI  - TMR and CABG: the best way to obtain a complete and a more lasting
      revascularization?

PMID- 10892984
TI  - Off-pump surgery and chronic renal insufficiency.

PMID- 10892985
TI  - A critical analysis of isolation of Paracoccidioides brasiliensis from soil.
AB  - The present review is a critical analysis of positive and negative reports of the
      isolation of Paracoccidioides brasiliensis from soil. The strains isolated from
      soil or soil-contaminated material (dogfood, penguin feces) by Batista et al. in
      Recife, Brazil, Negroni in the Argentinian Chaco, Albornoz in rural Venezuela,
      Silva-Vergara et al. in Ibia, Brazil, Ferreira et al. in Uberlandia, Brazil, and
      Gezuele et al. at the Uruguayan base in the Antarctic region, presented
      mycological characteristics consistent with P. brasiliensis. In most of these
      studies, morphological characterization was complemented with an evaluation of
      virulence and antigenicity, and biochemical or molecular analysis. These
      isolations, therefore, can be considered true, supporting the concept of soil as
      an important element in the ecology of the pathogen. The large number of negative
      reports in attempts involving soil samples and the low repeatability of isolation
      of the fungus from the same area indicate that the specific conditions supporting
      growth of the pathogen in soil have not been fully clarified.

PMID- 10892986
TI  - Isolation of Paracoccidioides brasiliensis from armadillos (Dasypus novemcinctus)
      in an area where the fungus was recently isolated from soil.
AB  - Natural infection of armadillos (Dasypus novemcinctus) with Paracoccidioides
      brasiliensis in Northern Brazil was reported in 1986, raising great interest in
      the understanding of the role of this mammal in the epidemiological cycle of the
      fungus. Recently, P. brasiliensis was isolated from the soil of Ibia, State of
      Minas Gerais, southeastern Brazil. Armadillos captured in this area were
      evaluated for the presence of P. brasiliensis in the viscera and infection was
      detected in 4/16 animals (25%). Fungal yeast phase cells were observed in three
      of the four infected armadillos by direct microscopic examination and by the
      indirect immunofluorescence test carried out on homogenized tissues. P.
      brasiliensis was isolated from three armadillos whose homogenized viscera had
      been injected into Swiss mice. The new strains (Ibia-T1, Ibia-T2 and Ibia-T3)
      were identified as P. brasiliensis on the basis of macro- and micromorphology,
      thermodimorphism, production and serologic activity of exoantigens, and by
      polymerase chain reaction (PCR)-detection of the gp43 gene. The lethality and
      lesions caused to the mice from which the strains were recovered confirmed the
      virulence of the isolates. We conclude that P. brasiliensis infects armadillos in
      locations with different geoclimatic characteristics and vegetation cover. The
      direct observation of yeast cells in tissues and the multiple visceral
      involvement, including the lungs, suggests the occurrence of
      paracoccidioidomycosis disease in these mammals and supports their role as wild
      hosts in the epidemiological cycle of the fungus.

PMID- 10892987
TI  - Timed-kill curves for Cryptococcus neoformans isolated from patients with AIDS.
AB  - Infection with Cryptococcus neoformans is an increasing problem in
      immunocompromised patients, particularly those with acquired immune deficiency
      syndrome (AIDS). Amphotericin B and fluconazole are currently acceptable
      therapies for cryptococcal meningitis; however, their effects remain suboptimal
      and recurrence or treatment failure is still a problem. Antifungal susceptibility
      testing may be an important tool for guiding therapy, but for C. neoformans, a
      reliable method is still not available. This retrospective study evaluated
      minimal inhibitory concentration (MIC) for amphotericin B and fluconazole, and
      minimal fungicidal concentration (MFC) and timed-kill curves for amphotericin B
      against 16 clinical isolates of C. neoformans obtained from AIDS patients with
      cryptococcal meningitis. No correlation between clinical outcome and MIC was
      observed for amphotericin B. In selected cases, the MFC seemed to be a better
      predictor of outcome than MIC. In this study, amphotericin B timed-kill curves
      appeared to show a correlation with clinical outcome of the 16 patients with AIDS
      associated cryptococcal meningitis. These in vitro tests must be further
      evaluated in prospective studies to confirm their potential usefulness for
      guiding cryptococcal meningitis therapy.

PMID- 10892988
TI  - Effect of grapefruit juice on serum voriconazole concentrations in the mouse.
AB  - Voriconazole is a broad spectrum, triazole antifungal drug now well into the
      final phases of clinical trials in humans. During preclinical phases of
      development, it was found that when administered to mice, one of the more
      important animals used in the in vivo evaluation of antifungal compounds, serum
      voriconazole concentrations were very low at best and often undetectable. This
      was due to a combination of high clearance and extensive metabolism by cytochrome
      P450 enzymes. As a result, mice were abandoned as being suitable for further
      study of voriconazole and most subsequent work with voriconazole has been
      performed in the guinea pig. In this study, we show that the administration of
      grapefruit juice, a known inhibitor of cytochrome P450 enzymes, is effective in
      producing measurable serum concentrations of voriconazole in mice when the drug
      is administered once daily. Serum voriconazole concentrations were < 3 microg ml(
      1) at all time points in mice not receiving grapefruit juice. In contrast,
      grapefruit juice administered by once daily gavage or continuously in lieu of
      water in the water bottle resulted in serum voriconazole concentrations ranging
      0.4-2.6 and 1.8-5.8 microg ml(-1), respectively, with increasing concentrations
      observed over the 10-day evaluation period. Further studies to elucidate the
      precise mechanism of action and optimal dosing schedule in mice can now be
      performed to improve our understanding of the pharmacokinetics of voriconazole in
      the mouse.

PMID- 10892989
TI  - Treatment of orogastrointestinal candidosis in SCID mice with fluconazole alone
      or in combination with recombinant granulocyte colony-stimulating factor or
      interferon-gamma.
AB  - Mucosal candidosis is common in acquired immune deficiency syndrome (AIDS)
      patients, where there is extensive mucosal involvement, but rarely dissemination.
      To mimic this disease, SCID mice were inoculated orally with Candida albicans,
      which could be recovered from standardized tissue samples of the esophagus,
      stomach, small intestine and caecum of all mice. Treatment with fluconazole at 5
      or 10 mg kg(-1) per day were equivalent to each other and efficacious in reducing
      the fungal burden from all four tissues compared with no treatment or lower doses
      of fluconazole (P < 0.01-0.001). Fluconazole at 5 or 10 mg kg(-1) reduced fungal
      burden in the stomach by about 200 or 580-fold, respectively, and by
      approximately 25-fold in the other tissues, with 80 or 100% of mice cleared of
      esophageal infection, and 40 or 80% cleared of infection in the small intestine,
      respectively; the same doses cleared < or =20% of stomach infection and none of
      caecal infection. Treatment with recombinant human granulocyte colony-stimulating
      factor (G-CSF) up to 500 microg kg(-1) per day or 10(5) U of murine interferon
      gamma (IFN-gamma) alone was ineffective, nor were combinations with a suboptimal
      dose fluconazole synergistic. Overall, fluconazole had dose-responsive efficacy,
      whereas neither G-CSF nor IFN-gamma alone or in combination with fluconazole
      improved efficacy. These studies demonstrate the utility of this model for
      examining antifungal efficacy in a situation that mimics clinical disease in AIDS
      patients.

PMID- 10892991
TI  - Production of IFN-gamma is impaired in patients with paracoccidioidomycosis
      during active disease and is restored after clinical remission.
AB  - Cellular immunity is usually suppressed during paracoccidioidomycosis (PCM) and
      is restored after treatment. In this study we evaluated the induction of a type 1
      (interferon gamma (IFN-gamma)), a type 2 (interleukin (IL)-10) and a primarily
      macrophage derived cytokine (tumor necrosis factor (TNF)-alpha) in peripheral
      blood mononuclear cells (PBMC) from patients with PCM. Eight male patients with
      active PCM, nine male patients with clinical remission of the disease and 10
      healthy control subjects were enrolled in the study. Cytokines were induced with
      non-specific stimuli --phytohaemagglutin (PHA) (induces IL-10 and IFN-gamma),
      Lipopolysaccharide (induces TNF-alpha)--and Paracoccidioides brasiliensis antigen
      (PbAg) (induces IL-10, IFN-gamma and TNF-alpha). Induction of IFN-gamma with PHA
      differed among the three groups (P < 0.01; Kruskal-Wallis test) and with PbAg was
      lower in patients with active disease compared to those in clinical remission (P
      = 0.05; Mann-Whitney). Induction of IL-10 and of TNF-alpha was similar in the
      three groups. The suppressed production of IFN-gamma in patients with active
      disease may underscore the cellular immune deficiency seen in these patients.

PMID- 10892990
TI  - Treatment of murine cryptococcal meningitis with UR-9751 and UR-9746.
AB  - In these studies, we compare the efficacy of two new azole antifungals with
      fluconazole in a murine model of cryptococcal meningitis. Mice were infected
      intracranially. Beginning one day later, groups of 7-10 mice were treated through
      to day 10 orally with UR-9751 or UR-9746 at 0.1, 0.25, 0.5, 1 or 10 mg kg(-1)
      day(-1) or fluconazole at 10 mg kg(-1) day(-1). At 10 mg kg(-1) day(-1), all
      three drugs prolonged survival over controls, but at 1 mg kg(-1) day(-1) only UR
      9746 prolonged survival. Tissue counts were more varied on mice sacrificed 8 days
      after infection. In general, both UR drugs were equal or more potent than
      fluconazole, and UR-9751 was more effective than UR-9746.

PMID- 10892992
TI  - Vital staining of fungal elements in deep-seated mycotic lesions during
      experimental murine mycoses using the parenterally applied optical brightener
      Blankophor.
AB  - Optical brighteners of the diaminostilbene type are fluorescent dyes which are
      popular diagnostic tools in the mycology laboratory. While these dyes are
      conventionally used for the in vitro diagnosis of mycoses, their low toxicity and
      chemical reactivity have led us to investigate their potential use for in vivo
      staining of fungal elements in mycotic tissue. In mice we have established deep
      seated candidiasis, cryptococcosis, aspergillosis and zygomycosis, as well as
      coccidioidomycosis, histoplasmosis and blastomycosis. After establishment of
      infection, which mostly required immunosuppression, a single dose of 100 microl
      of an aqueous solution (2.2 x 10(-4) M) of the optical brightener Blankophor P
      fluessig (4,4'-Bis [(4-anilino-6-substituted-1,3,5-triazine-2-yl) amino] stilbene
      2,2'-disulfonic acid) was injected by the tail vein and the animals were
      sacrificed 1 h later. Sections of freshly prepared target organs were directly
      subjected to epifluorescence microscopy using an appropriate filter kit. In most
      cases, fluorescent fungal elements could be detected in the murine tissue. There
      was little evidence for uptake of the dye by non-infected tissues. It is
      suggested that radioactive labeling may render parenteral Blankophor suitable for
      radiographic localization of deep-seated mycotic foci in the host.

PMID- 10892993
TI  - The effects of lipid extraction on the immunomodulatory activity of Malassezia
      species in vitro.
AB  - Malassezia spp. are believed to be the causative agents of pityriasis versicolor
      and are strongly implicated in seborrhoeic dermatitis. The yeast also forms part
      of the normal human cutaneous microflora. We have previously shown that when
      Malassezia yeast cells are incubated with human peripheral blood mononuclear
      cells (PBMCs), they are capable of reducing the levels of pro-inflammatory
      cytokines produced. In order to test the hypothesis that this immunoevasive
      phenomenon may be related to the unusually high level of lipid in the Malassezia
      yeast cell wall, we have compared the immunomodulatory capacity of normal and
      lipid-depleted yeast cells. Stationary phase yeast cells of Malassezia
      sympodialis, M. globosa and M. restricta were treated with chloroform/methanol to
      extract the surface lipids. The lipid-depleted and non-depleted yeast cells were
      then co-cultured with human PBMCs from three different human donors at a ratio of
      20 yeasts per leukocyte for 24 h. The levels of interleukin (IL)-1beta, IL-6 and
      tumour necrosis factor (TNF)-alpha were then determined by enzyme-linked
      immunosorbent assay (ELISA). The results demonstrated that extraction of lipid
      reversed the yeast cell capacity to reduce the levels of pro-inflammatory
      cytokines. The levels of IL-1beta, IL-6 and TNF-alpha produced in response to
      lipid-extracted Malassezia of all three species were either no different from or
      significantly greater (P < 0.05; ANOVA) than the constitutive control levels.
      These results suggest that the lipid microfibrillar layer of Malassezia may
      prevent the yeast cells from inducing inflammation and provide an explanation for
      the normal commensal status of the organism on human skin. The hypothesis that
      the lipid layer is absent or altered in seborrhoeic dermatitis may provide an
      explanation for the inflammatory nature of this dermatosis.

PMID- 10892994
TI  - Granulomatous skin lesions due to histoplasmosis in a badger (Meles meles) in
      Austria.
AB  - We describe the first case of histoplasmosis due to infection with Histoplasma
      capsulatum var. capsulatum in a wild badger (Meles meles) in Austria. Diagnosis
      was established by histopathological and immunohistochemical characterization of
      yeast forms in skin lesions and lymph nodes. Although Austria has yet to be
      regarded as an endemic region for H. capsulatum, infections of animals and humans
      exposed to contaminated soil cannot be excluded.

PMID- 10892995
TI  - Characterization of immune response of young pigs to porcine circovirus type 2
      infection.
AB  - A longitudinal study was conducted to characterize the immune response of young
      swine to infection with porcine circovirus type 2 (PCV-2). Five 8-week-old
      cesarean-derived, colostrum-deprived pigs were inoculated intranasally and
      intramuscularly with a field isolate of PCV-2 at a concentration of 10(4)
      TCID50/mL. Along with monitoring for clinical signs and viremia, serum samples
      were collected from all pigs at day 0 and thereafter every 7 days postinoculation
      (PI) until the termination of the study on day 35 PI. No clinical signs were
      observed in any of the animals during the study period. In all pigs, PCV-2 was
      detected by polymerase chain reaction (PCR) in serum samples collected on days 7,
      14, and 21 PI. Viral DNA and antigens were detected by in situ hybridization and
      immunohistochemistry in tonsil, spleen, medial iliac lymph nodes, and ileum
      collected from each pig at the end of the study. Collectively, naive young swine
      were shown to be susceptible to PCV-2. Virus-specific antibody was detected by an
      indirect fluorescent antibody (IFA) assay on day 14 PI, but virus-neutralizing
      antibody was not detected until day 28 PI. As neutralizing antibodies developed,
      cross-reactivity with PCV type 1 (PCV-1) also developed on the IFA test. Western
      immunoblot analysis revealed three PCV-2 proteins with molecular masses of 28 kd,
      28.5 kd, and 35 kd. The 35-kd protein was also demonstrated in PCV-1, suggesting
      that this protein induced the cross-reactivity between PCV types 1 and 2.
      Antibody to the 28-kd protein was detected on day 14 PI and later, indicating
      that this protein was the most immunogenic. Because of its immunogenicity and
      specificity to PCV-2, and 28-kd protein might provide the antigenic basis for the
      development of diagnostic tests for detection of PCV-2 antibody.

PMID- 10892996
TI  - Immunogenicity evaluation of DNA vaccines that target guinea pig cytomegalovirus
      proteins glycoprotein B and UL83.
AB  - Vaccines are needed for control of congenital human cytomegalovirus (HCMV)
      infection. Although the species-specificity of cytomegaloviruses precludes
      preclinical evaluation of HCMV vaccines in animal models, the guinea pig
      cytomegalovirus (GPCMV), which causes disease in utero, is a relevant model for
      the study of vaccines against congenital infection. We investigated whether DNA
      vaccines that target two GPCMV proteins, glycoprotein B (gB) and UL83 (pp65), are
      capable of eliciting immune responses in vivo. After cloning each gene into an
      expression vector, DNA was delivered by intramuscular inoculation and by
      pneumatic epidermal delivery. In Swiss-Webster mice, anti-gB titers were
      significantly higher after epidermal delivery. After epidermal inoculation in
      guinea pigs, all gB-immunized animals (n = 6) had antibody responses comparable
      to those induced by natural infection. Viral neutralization titers ranged from
      1:64 to greater than 1:128. A GPCMV UL83 DNA vaccine also elicited an antibody
      response in all immunized guinea pigs (n = 6) after epidermal administration.
      Immunoprecipitation and Western blot assays confirmed that immune sera were
      immunoreactive with virion-associated UL83 and gB proteins. We conclude that DNA
      vaccines against GPCMV structural proteins are immunogenic, and warrant further
      investigation in the guinea pig model of congenital CMV infection.

PMID- 10892997
TI  - Augmentation of immune responses to hepatitis E virus ORF2 DNA vaccination by
      codelivery of cytokine genes.
AB  - DNA vaccines encoding a viral structural protein have been shown to induce
      antiviral immune responses and provide protection against subsequent viral
      challenge. In the present study we show that DNA immunization with a plasmid
      expressing the hepatitis E virus ORF2 structural protein (pcDNA-ORF2) induced low
      levels of long-lasting antibody responses in the murine model. The use of
      plasmids expressing interleukin-2 (IL-2) and granulocyte-macrophage colony
      stimulating-factor (GM-CSF) in conjunction with pcDNA-ORF2 enhanced the antibody
      responses generated by pORF-2. We further show that the immune responses
      generated by plasmid pcDNA-ORF2 can be boosted with virus-like particles composed
      of the ORF2 protein expressed through a baculovirus expression system.

PMID- 10892998
TI  - T-cell activation and induction of antibodies and memory T cells by immunization
      with inactivated Japanese encephalitis vaccine.
AB  - Mouse brain-derived inactivated Japanese encephalitis (JE) vaccine is the only
      currently internationally accepted vaccine against JE virus. We analyzed cellular
      and humoral immune responses to the JE vaccine in healthy adults in order to
      understand the protective immunity induced by this vaccine. Immunization with the
      JE vaccine induced T-cell activation in vivo, demonstrated by increase in the
      plasma levels of interleukin (IL)-2 and soluble CD8. JE virus-specific antibodies
      determined in radioimmunoprecipitation (RIP), hemagglutination inhibition (HI),
      and neutralization assays were also induced by immunization with the JE vaccine.
      JE virus-specific memory T cells were detected 60 days after immunization. These
      results suggest that protective immunity induced by the inactivated JE vaccine
      includes JE virus-specific T cells as well as antibodies with multiple biological
      activities.

PMID- 10892999
TI  - Homotypic protection against rotavirus-induced diarrhea in infant mice breast-fed
      by dams immunized with the recombinant VP8* subunit of the VP4 capsid protein.
AB  - The outer capsid proteins VP4 and VP7 induce neutralizing antibody against
      rotavirus. We have investigated in a mouse model the protection mediated by
      immunization with VP8*, the amino-terminal tryptic fragment of VP4. BALB/c female
      mice immunized with simian rotavirus SA11 VP6 and VP8* proteins expressed in
      Escherichia coli were mated with seronegative males. Litters were orally
      challenged with the SA11 strain (P5B[2], G3) or with the murine rotavirus strain
      EDIM (P10[16], G3) to verify the degree of protection against diarrhea induced in
      the newborns. Only those pups born to dams immunized with VP8* did not develop
      diarrhea after having been orally challenged with the SA11 strain. Pups born to
      naive dams but foster nursed by VP8*-immunized dams did not develop diarrhea
      after having been orally infected with the SA11 strain, but they suffered
      diarrhea when challenged with the EDIM strain. These results support the concepts
      that (1) VP8* is a highly immunogenic polypeptide that induces effective
      homotypic protection against disease in pups born to dams immunized with this
      antigen and (2) in newborn mice the protection against disease is mediated by
      neutralizing secretory antibodies present in the milk rather than by serum
      antibodies transferred through the placenta to the offspring.

PMID- 10893000
TI  - Identification and localization of conserved antigenic epitopes on the G2
      proteins of California serogroup Bunyaviruses.
AB  - California (CAL) serogroup Bunyaviruses are significant agents of arboviral
      encephalitis in humans. They are maintained and transmitted in nature by
      mosquitoes to preferred vertebrate amplifying hosts. The G2 envelope glycoprotein
      of La Crosse virus (LAC) was proposed by Ludwig et al. to be a determinant for
      virus attachment to mosquito midgut cells. Monoclonal antibodies to G2 neutralize
      the infectivity of pronase-treated virus for mosquito cells. We determined the
      location of antigenic sites on the LAC G2. We showed that antigenic areas present
      on the LAC G2 protein are conserved among viruses in the California encephalitis
      and Melao subgroups of the CAL serogroup, but not in trivatattus virus, nor
      within the BUN serogroup. A comparison of the G2 exodomain amino acid sequences
      of eight CAL and three BUN viruses with monoclonal antibodies (MAb) binding data
      predicted the possible location of the antigenic sites. We used in vitro
      mutagenesis of the LAC G2 gene to construct a set of G2 genes with replacement
      sequences in the coding regions for the suspected MAb binding sites. The native
      and mutated proteins were expressed in Hela cells and the ability of MAbs to bind
      to the expressed proteins was tested. Four discontinuous amino acid sequences,
      conserved among eight CAL serogroup viruses, were identified as contributing to
      two conformational binding domains for neutralizing LAC G2 MAbs.

PMID- 10893001
TI  - Inhibition of cell growth and Epstein-Barr virus reactivation by CD40 stimulation
      in Epstein-Barr virus-transformed B cells.
AB  - The CD40 molecule plays important roles in B cell activation, proliferation, and
      immunoglobulin (Ig) class switching. In Epstein-Barr virus (EBV)-transformed
      lymphoblastoid cell lines (LCL), CD40 mediates growth inhibition and EBV
      reactivation via the CD40 signaling pathways. CD40 cross-linking with a
      monoclonal antibody arrests cell growth in G1 and induces expression of p27kip1
      cyclin-dependent kinase inhibitor. CD40 cross-linking also induces EBV
      reactivation, as detected by the induction of EBV-specific early antigen,
      immediate early BZLF1 RNA, and its protein product ZEBRA. These results support
      hypotheses that the proliferation of EBV-infected B cells in vivo can be
      inhibited by interactions with the CD40 ligand on activated helper T cells, and
      latent EBV is reactivated via the signaling pathways controlled by CD40
      interactions.

PMID- 10893002
TI  - Enhanced pulmonary pathology in cotton rats upon challenge after immunization
      with inactivated parainfluenza virus 3 vaccines.
AB  - Vaccine-induced potentiation was studied in cotton rats immunized with formalin
      inactivated human parainfluenza type 3, ultraviolet light-inactivated virus, or
      infection with live virus. Immunized animals and unimmunized controls were later
      challenged by intranasal inoculation of live virus and evaluated for pulmonary
      pathology 4 days later. Animals immunized with either of the inactivated vaccines
      developed marked peribronchiolitis, perivasculitis, and an alveolar cellular
      infiltration much more severe than seen in animals infected previously, or in
      unmanipulated but challenged animals. Disease enhancement after immunization with
      killed virus is thus a characteristic of a member of each of three genera of the
      family, Paramyxoviridae, and is not restricted to immunization with formalin
      inactivated virus.

PMID- 10893003
TI  - Systemic and mucosal isotype-specific antibody responses in pigs to experimental
      influenza virus infection.
AB  - The immunoglobulin isotype-specific responses in serum and at the respiratory
      mucosa of pigs after a primary infection with influenza virus were studied. To do
      this, we developed an aerosol challenge model for influenza in specified pathogen
      free (SPF) pigs and isotype-specific enzyme-linked immunosorbent assays (ELISAs).
      Ten-week-old pigs were inoculated without anesthesia in the nostrils with an
      aerosol of the field isolate influenza A/swine/Neth/St. Oedenrode/96 (H3N2). The
      infection caused acute respiratory disease that closely resembled the disease
      observed in some outbreaks of influenza among finishing pigs, which were not
      complicated by bacterial infections. Pigs showed clinical signs characterized by
      fever, dyspnea, and anorexia. At necropsy on postinfection days 1 and 2, an
      exudative endobronchitis was observed throughout the lung. Viral antigen was
      present in the epithelial cells of the bronchi and bronchioli and virus was
      isolated from bronchioalveolar and nasal lavage fluids and from pharyngeal swabs
      until 5 days after infection. With the isotype-specific ELISAs, viral
      nucleoprotein specific immunoglobulin (Ig) M, IgG1, and IgA antibody responses
      were measured in serum and bronchioalveolar and nasal lavage fluids. To determine
      whether the antibodies were produced and secreted at the respiratory mucosa or
      were serum-derived, the specific activity (ie, the ratio of antibody titer to Ig
      concentration) was calculated for each isotype. The IgA and interestingly also a
      substantial part of the IgG1 antibody response in pigs upon infection with
      influenza virus was shown to be a mucosal response. Local production of specific
      IgA in the nasal mucosa, and of specific IgA and IgG1 in the lung was
      demonstrated. These results indicate that protective efficacy of vaccination can
      be improved by an immunization procedure that preferentially stimulates a mucosal
      immune response. The aerosol challenge model in SPF pigs and the isotype-specific
      ELISAs that we developed can be useful for evaluating various strategies to
      improve efficacy of porcine influenza vaccines and to study the immune mechanisms
      underlying the observed protection.

PMID- 10893005
TI  - Quality versus quantity.

PMID- 10893004
TI  - Determinants of immune defense against microbial infections: Santa Fe, New
      Mexico, February 24-29, 2000.

PMID- 10893006
TI  - Anti-neutrophil cytoplasmic antibodies directed against the
      bactericidal/permeability-increasing protein (BPI) in pediatric cystic fibrosis
      patients do not recognize N-terminal regions important for the anti-microbial and
      lipopolysaccharide-binding activity of BPI.
AB  - This study was performed to examine the prevalence and clinical correlates of
      bactericidal/permeability-increasing protein anti-neutrophil cytoplasmic
      antibodies (BPI-ANCA) in pediatric cystic fibrosis (CF) patients and to elucidate
      their possible role in CF pulmonary pathology. Sera of 27 CF patients were tested
      for ANCA by indirect immunofluorescence (IFT) and by enzyme-linked immunosorbent
      assay (ELISA) for ANCA sub-specificities. BPI-ANCA were examined by using
      standard ELISA for BPI, lipopolysaccharide-binding protein (LBP), and BPI/LBP
      fusion proteins to epitope map the main binding sites and look for cross
      reactivity with LBP. Pulmonary function and serum concentrations of total
      immunoglobulin G (IgG) were measured and infections were diagnosed. In addition,
      release of reactive oxygen species (ROS) by neutrophil granulocytes was measured
      after stimulation with monoclonal BPI-ANCA. Using IFT, two patients showed
      atypical ANCA staining, six patients exhibited perinuclear ANCA staining, and no
      cytoplasmic ANCA staining was detected. Of 27 patients, 13 (48%) were BPI-ANCA
      (IgG) positive, and three were also immunoglobulin A (IgA) BPI-ANCA positive; one
      patient had ANCA against lactoferrin; and no proteinase 3 ANCA was detected in
      any of the patients. All BPI-ANCA bound to the C-terminal region of the molecule;
      none bound to the N-terminus or to LBP. There was no significant correlation
      between clinical data and the occurrence of BPI-ANCA in this cross-sectional
      study. Release of ROS from granulocytes was induced by monoclonal BPI-ANCA.
      Activation of neutrophils and possible modulation of BPI-mediated
      opsonophagocytosis and disposal of Gram-negative bacteria and lipopolysaccharides
      by BPI-ANCA raise the possibility that they contribute to pulmonary pathology in
      pediatric CF patients but intervention longitudinal studies in large groups of
      patients are needed to establish a causative association.

PMID- 10893007
TI  - Synthetic pillows contain higher levels of cat and dog allergen than feather
      pillows.
AB  - The use of non-feather pillows has increased over the last few decades. Recently,
      we found significantly higher levels of dust mite allergens in synthetic pillows
      than in feather ones. This study investigated the levels of pet allergens in
      feather and synthetic pillows. Dust samples were collected from 14 pairs of
      pillows (consisting of one synthetic fibre-filled and one feather-filled). Each
      pair of pillows had been on the same bed for at least 2 years. The pillows were
      vacuumed for 1 min on each side through a 355-microm diameter mesh onto a 5
      microm vinyl filter, producing a sample of fine dust. Samples were extracted, and
      cat (Fel d 1) and dog (Can f 1) allergens determined using monoclonal antibody
      based enzyme-linked immunosorbent assay (ELISA). Results were expressed both as
      total amount of allergen recovered and concentration of allergen per unit weight
      (ng/g). Total levels of pet allergens were significantly higher in the synthetic
      pillows (Fel d 1: 6.7-fold difference [95% CI 1.5-29.7], p=0.01; Can f 1: 8-fold
      difference [95% CI 1.6-39.5], p=0.01). Similarly, when the results were expressed
      as ng/g, synthetic pillows contained significantly more allergens than feather
      pillows (Fel d 1: 3.7-fold difference [95% CI 1.3-10.1], p=0.01); Can f 1: 4.4
      fold difference [95% CI 1.5-13.2], p=0.01). We have therefore demonstrated that
      synthetic pillows contain significantly more pet allergens than feather pillows,
      supporting the view that tightly woven encasements surrounding feather pillows
      act as a barrier for allergens.

PMID- 10893008
TI  - Asthma in children: prevalence, treatment, and sensitization.
AB  - This study compares the prevalence of asthma and sensitization in children from
      two Swedish regions with different climates: Goteborg on the southwest coast and
      Kiruna in the northern inland, north of the Arctic Circle. The 412 children of a
      population-based sample, 203 in Goteborg and 209 in Kiruna, were investigated at
      age 7-8 and 12-13 years. Questionnaire reports and interviews were obtained from
      all children at 7-8 years of age, and 192 children were skin-prick tested for
      common aeroallergens in Goteborg and 205 in Kiruna. At the follow-up, 5 years
      later, almost all the children were re-investigated. The prevalence of asthma,
      wheeze, and sensitization had increased with increasing age during the follow-up
      period. The questionnaire reports revealed that the prevalence of asthma was 8.5%
      at 12-13 years of age. All children who in the questionnaire reported current
      asthma, were using asthma medication. The interviews indicated that the
      prevalence of a clinically significant asthma might be even higher, reaching
      approximately 12%. Asthma and wheeze were as common in Goteborg as in Kiruna
      despite large differences in prevalence of sensitization. Sensitization, and
      especially sensitization to animals, was far more common in Kiruna than in
      Goteborg. This study shows that asthma and wheeze are increasingly prevalent even
      in school age children and that sensitization does not necessarily reflect the
      prevalence of asthma in a population.

PMID- 10893009
TI  - Connections among parent and child atopic illnesses.
AB  - This study investigated parent-child connections for the atopic illnesses of
      asthma, eczema, food allergies, and hay fever, in a sample of 325 families.
      Parents reported whether they or their children currently had each condition and
      rated the frequency and intensity of its episodes; these ratings were combined to
      estimate illness severity. The data revealed five main findings. First, chi
      square parent-child concordance analyses indicated that children of parents with
      any of the atopic illnesses studied were significantly more likely to develop
      that same disease than were children of parents without the illness. Second,
      children were progressively more likely to have at least one atopic illness when
      the number of their parents who were atopic increased from zero to two. Third,
      the number of atopic illnesses in the children was associated with the number of
      atopic illnesses in the parents. These three findings augment the evidence for
      genetic factors in the development of atopic illnesses and suggest that the
      atopies of each parent may contribute to an aggregate, generalized risk for their
      children. Fourth, maternal atopy was more strongly related to the children's
      asthma and hay fever than paternal atopy. Fifth, the severity of the children's
      specific atopic illnesses was not affected by the number of their parents who had
      the same condition and was not strongly related to the severity of their parents'
      condition.

PMID- 10893010
TI  - Evaluation of a clinical algorithm involving serum eosinophil cationic protein
      for guiding the anti-inflammatory treatment of bronchial asthma in childhood.
AB  - A pilot study was performed to investigate a clinical algorithm using serum
      eosinophil cationic protein level (S-ECP) as an objective parameter for tapering
      the anti-inflammatory treatment in chronic childhood asthma. We studied 21
      outpatient asthmatic children (6 girls and 15 boys, mean age 9 yr, range 3-12 yr,
      all with initial S-ECP > or = 15 microg/l) over a period of 12 months at monthly
      intervals. At each visit a short history, clinical examination, blood sample for
      S-ECP and eosinophil count, lung function tests and drug compliance were
      assessed. According to the initial S-ECP, patients were allocated to two anti
      inflammatory treatment groups: patients with S-ECP between 15 microg/l and 30
      microg/l were treated with Budesonide 200 microg twice daily, while patients with
      S-ECP of 30 microg/l and above received Budesonide 400 microg twice daily. After
      this induction treatment the anti-inflammatory medication was tapered at monthly
      intervals according to actually measured S-ECP: patients with S-ECP < 15 microg/l
      received sodium cromoglycate (SCG) 10 mg twice daily per inhalation via spacer,
      patients with S-ECP > or = 15 microg/l and < 30 microg/l received Budesonide 200
      microg twice daily via spacer, and patients with S-ECP > or = 30 microg/l
      received Budesonide 400 microg twice daily. Prior to inhalation of topical
      steroids or SCG all patients had to inhale 500 microg Terbutaline twice daily for
      optimal bronchodilatation. The use of medication was assessed by weighing the
      metered dose inhaler containers each month. Our results showed a decrease in
      symptoms (p = 0.0001) and in S-ECP (p= 0.02) and MEF50% predicted (p= 0.02) after
      the initial month of Budesonide treatment. During a total of 246 months of
      investigation there was no need for emergency room treatment or hospital
      admission, and no need for oral steroids. During the whole study period there was
      a tendency for inhaled steroids to be more effective than SCG in reduction of
      markers of airway inflammation, improvement of symptoms and lung function.
      Inadequate use of medication was related to an increase in S-ECP in all treatment
      groups. From this open pilot study it is concluded that a clinical algorithm
      including S-ECP for tapering the anti-inflammatory treatment may be helpful in
      childhood asthma. These first observations should be confirmed by a controlled
      long-term study.

PMID- 10893011
TI  - Diagnosis of IgE-mediated food allergy among Swiss children with atopic
      dermatitis.
AB  - Diagnosis of food allergy in children with atopic dermatitis (AD) relies on a
      good knowledge of the prevalence of the disease and of the foods most frequently
      involved. Our objective was to define these characteristics in a population-of
      Swiss children with AD. Patients referred to a pediatric allergist or a
      dermatologist for AD were routinely tested by skin-prick test (SPT) to seven
      common food allergens (milk, egg, peanut, wheat, soy, fish, and nuts), and to all
      other foods suspected by history. Patients with positive SPTs were further
      evaluated for specific serum immunoglobulin E (IgE) antibodies (by using the CAP
      System FEIA ). CAP values were interpreted following previously published
      predictive values for clinical reactivity. Patients with inconclusive results
      (between the 95% negative predictive value [NPV] and the 95% positive predictive
      value [PPV]) were challenged with the suspected food. A total of 74 children with
      AD were screened for food allergies. Negative SPTs excluded the diagnosis in 30
      subjects. Nineteen patients were diagnosed by histories suggestive of recent
      anaphylactic reactions to foods and/or CAP values above the 95% PPV. Forty-three
      food challenges (35 open challenges and eight double-blind, placebo-controlled in
      children with persistent lesions of AD despite aggressive topical skin treatment)
      were performed in patients with positive SPTs but with inconclusive CAP values.
      Six patients were diagnosed as positive to 15 foods. Challenges were not
      performed to high-allergenic foods in young children (under 12 months of age for
      egg and fish, and under 3 years of age for peanuts and nuts). Altogether, 33.8%
      (25 of 74) of the AD patients were diagnosed with food allergy. The prevalence of
      food allergy was 27% (seven of 25) in the group referred to the dermatologist for
      primary care of AD. The foods most frequently incriminated were egg, milk, and
      peanuts. The prevalence of food allergy in our population was comparable to that
      in other westernized countries, suggesting an incidence of food allergy in
      approximately one-third of children with persistent lesions of AD. Together with
      milk and eggs, peanuts were most frequently involved in allergic reactions.

PMID- 10893012
TI  - Helicobacter pylori seropositivity in children with atopic dermatitis as sole
      manifestation of food allergy.
AB  - A positive association between Helicobacter pylori antibodies and food allergy
      presenting with gastrointestinal symptoms has recently been reported. A subset of
      a H. pylori strain possesses an antigen, CagA, as a virulence factor. Anti-H.
      pylori and anti-CagA IgG titre have been determined in children with atopic
      dermatitis (AD) as the sole clinical manifestation of food allergy. In this
      study, thirty patients with AD as the sole clinical manifestation of food allergy
      were examined (group A). For comparative purposes, 30 patients affected by food
      allergy with gastrointestinal symptoms (group B) and 30 affected by atopic asthma
      (group C) were studied. Anti-H. pylori and anti-CagA immunoglobulin G (IgG) were
      determined in all individuals by means of the enzyme-linked immunosorbent assay.
      The anti-H. pylori IgG titre was significantly higher in group A and group B vs.
      group C (p < 0.05); no significant difference was detected between group A and
      group B (p > 0.05). No significant difference in anti-CagA titre was found
      between the groups. These data demonstrate a positive association between H.
      pylori antibodies and AD as the sole manifestation of food allergy. Further
      investigations are needed to evaluate the cause-effect relationship between H.
      pylori seropositivity and AD.

PMID- 10893013
TI  - Identification of immunogenic maize proteins in a casein hydrolysate formula.
AB  - Cow's milk-based formulas used for infants with cow's milk allergy are based on
      hydrolyzed proteins. The formulas that are successful in preventing allergic
      responses are extensively hydrolyzed. Nevertheless, reactions to such formulas
      are occasionally reported, and protein material of higher molecular weight than
      expected has been detected by binding immunoglobulin E (IgE) from patients' sera.
      This paper presents the identification of high-molecular-weight material in the
      extensively hydrolyzed casein formula, Nutramigen. The material was concentrated
      by simple centrifugation. The proteins in the pellet were separated by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and protein
      containing bands were analyzed by protein sequencing after electroblotting. The
      proteins were identified as maize zeins, which are water-insoluble proteins of
      apparent M(r) 20,000 and 23,000, presumably originating from the maize starch in
      Nutramigen. Rabbits immunized with this formula developed antibodies against
      zeins but not against milk proteins. The maize zeins are probably identical to
      the recently reported components in Nutramigen (1), detected by binding of IgE
      from milk allergic patients, but not correlated to clinical allergic reactivity.
      The clinical relevance of maize proteins in Nutramigen remains to be established.

PMID- 10893014
TI  - Ventricular shunts and the prevalence of sensitization and clinically relevant
      allergy to latex in patients with spina bifida.
AB  - Patients with spina bifida represent the highest-risk group for developing
      hypersensitivity to latex. Recognized risk factors for these patients are
      repeated surgery and an atopic disposition. Our aim was to study the influence of
      a ventricular shunt as an independent risk factor. One hundred and sixty-one
      patients with spina bifida (median age 10 years) were investigated for the
      presence of a shunting device and the number, type and date of previous surgical
      interventions. Additionally, skin-prick tests and provocation tests were
      performed in order to classify sensitized and symptomatic latex-allergic
      individuals. Eighty-eight patients (54.7%) were sensitized; 55 (34.2%) were
      provocation-positive. Patients with a shunt system had undergone a significantly
      higher number of surgical procedures (p < 0.0001) and showed significantly higher
      levels of immunoglobulin E (IgE)-antibodies to latex (p < 0.0001) than patients
      without a shunting device. The total number of operations correlated
      significantly with the level of IgE-antibodies to latex in serum (p < 0.0001),
      whereas the number of shunt operations in patients with a ventricular shunt did
      not significantly correlate with the degree of sensitization. In conclusion,
      patients with spina bifida who have a ventricular shunt are at particularly high
      risk because they undergo a significantly higher number of operations than
      patients without a ventricular shunt. However, the ventricular shunt does not
      seem to be an independent risk factor. Furthermore, this study emphasizes that
      individuals at high risk, such as patients with spina bifida, should be handled
      latex-free from the very beginning of life.

PMID- 10893015
TI  - Clinical pharmacology of the H1-receptor antagonists cetirizine and loratadine in
      children.
AB  - H1-receptor antagonists are widely used in children but are not as well-studied
      in children as they are in adults. Our objective was to determine the onset and
      duration of action and the relative potency of the H1-receptor antagonists
      cetirizine and loratadine in children. We performed a prospective, randomized,
      placebo-controlled, double-blind, crossover, single-dose study of cetirizine and
      loratadine using suppression of the histamine-induced wheal and flare as the
      primary outcome. In 15 allergic children, mean age 9 years, compared with
      baseline, cetirizine (10 mg) suppressed the wheals and flares significantly from
      0.25 to 24 h, achieving nearly 100% of flare suppression from 2 to 24 h,
      inclusive, and loratadine (10 mg) suppressed the wheals and flares significantly
      from 0.75 to 24 h, inclusive. Cetirizine suppressed the wheals and flares
      significantly more than loratadine from 0.25 to 1 h, inclusive, and at 0.5, 1, 2,
      3, 5, 6, 7, and 24 h, respectively. Placebo also suppressed the wheal and flare
      significantly at some assessment times. Cetirizine and loratadine both have
      excellent antihistaminic activity in children, with a rapid onset of action and a
      24-h duration of action in this population.

PMID- 10893016
TI  - Low-dose budesonide improves exercise-induced bronchospasm in schoolchildren.
AB  - The aim of this study was to compare the clinical efficacy of low-dose inhaled
      budesonide (once or twice daily) and placebo, administered via Turbuhaler, on
      exercise-induced bronchoconstriction (EIB) in children with mild asthma. Fifty
      seven steroid-naive children (7-16 years old; 41 boys, 16 girls) with EIB
      participated in this sub-population study according to the following inclusion
      criterion: a maximum fall in forced expiratory volume in 1 s (FEV1) > or = 10%
      after a standardized treadmill test. Mean baseline FEV1 was 100.3% of predicted,
      and mean maximum fall in FEV1 after the standardized exercise test was 22%. The
      study was a double-blind, randomized, parallel-group design. After 2 weeks of run
      in, the children received inhaled budesonide 100 microg or 200 microg once daily
      in the morning, 100 microg twice daily, or placebo, for 12 weeks. After 12 weeks
      of treatment, the fall in FEV1 after the exercise test was significantly less in
      all three budesonide groups (7.2-7.8%) vs. placebo (16.7%). Daytime symptom
      scores were significantly lower in all three budesonide groups compared with
      placebo (p <0.02). The three budesonide groups did not differ significantly, and
      no significant change in lung function was found in any group. Therefore children
      with mild asthma, but with significant EIB, improved their exercise tolerance and
      symptom control after 3 months of treatment with a low dose of inhaled budesonide
      given once or twice daily.

PMID- 10893017
TI  - Cytokines in aging and exercise.
AB  - Aging is associated with increased inflammatory activity. Increased plasma levels
      of tumour necrosis factor (TNF)-alpha were found in centenarians aged 100 years
      and in individuals aged 80-81 years when compared to a young control group.
      Plasma levels of TNF-alpha were linearly correlated to plasma levels of
      interleukin (IL)-6, TNF-receptors and C-reactive protein. High levels of TNF
      alpha were directly related to dementia and to a low blood pressure ankle-arm
      index, indicating generalized atherosclerosis. In hospitalized patients with
      Streptococcus pneumonia infection, aging was associated with prolonged
      inflammatory activity. Similar results were found using an in vivo endotoxin
      challenge model in old versus young humans. Strenuous exercise induces increased
      levels in a number of proinflammatory and anti-inflammatory cytokines, naturally
      occurring cytokine inhibitors and chemokines. Thus, increased plasma levels of
      TNF-alpha, IL-1, IL-6, IL-1 receptor antagonist (IL-Ira), TNF-receptors (TNF-R),
      IL-10, IL-8 and macrophage inflammatory protein (MIP)-1 are found after strenuous
      exercise. The cytokine response to strenuous exercise has similarities to the
      cytokine response to trauma and sepsis. Therefore, in future studies, exercise is
      suggested as an ethically applicable model to use in studies on mechanisms
      underlying the age-associated altered cytokine response.

PMID- 10893018
TI  - Aging, immune function, and exercise: hormonal regulation.
AB  - There is a known decline in immune function associated with aging which increases
      the risk for infectious diseases, tumorigenesis, and autoimmune disorders. As a
      result, older individuals demonstrating age-related immune dysfunction have
      significantly higher mortality rates. Alterations in neuroendocrine function play
      an important role in this immunosenescence as reductions in the ability to
      synthesize and release hormones and neurotransmitters, alterations in receptor
      number, density and affinity, diminished receptor responsiveness, and alterations
      in biochemical events distal to the hormone/receptor site are known to occur. It
      is becoming increasingly apparent that these age-associated neuroendocrine
      changes have a significant regulatory role in modulating immune function both at
      rest and in response to the stress of a single bout of exercise. In particular,
      this review will focus on age-related changes that are documented to occur in
      growth hormone, IGF-I, sympathetic nerve activity, catecholamine metabolism and
      responsiveness, and gonadal steroids. As a result of these neuroendocrine
      changes, older individuals are likely to respond differently to both acute and
      chronic exercise stimulation.

PMID- 10893019
TI  - Exercise and neuroendocrine regulation of antibody production: protective effect
      of physical activity on stress-induced suppression of the specific antibody
      response.
AB  - It has been convincingly demonstrated that the in vivo immune response is not
      fully autonomous. Clearly, functional interactions exist between the
      neuroendocrine system and the immune system that operate during the generation of
      normal in vivo immune responses. In addition to playing an important regulatory
      role in the absence of perturbation, the same neuroendocrine signals that
      facilitate immune function in a nonstressed organism may suppress immune function
      in a physiologically or psychologically stressed organism. Given the complexity
      of these interactions, the current paper will focus on neuroendocrine modulation
      of one important dimension of acquired immunity, the in vivo antibody response to
      a benign protein (keyhole limpet hemocyanin, KLH). In addition, only the
      hypothalamic-pituitary-adrenal (corticosterone) response and the sympathetic
      nervous system (norepinephrine and epinephrine) response will be discussed. The
      current paper will 1) examine the cellular steps involved in the antibody
      response to KLH; 2) describe the specific cellular consequences of acute stressor
      exposure on this response; 3) describe the evidence for corticosterone and
      catecholamine modulation of the in vivo antibody response during quiescent and
      stressed states; and 4) present data that support the hypothesis that regular,
      moderate, physical activity can prevent the neuroendocrine and detrimental
      immunological effects of stress.

PMID- 10893020
TI  - Exercise immunology: neuroendocrine regulation of NK-cells.
AB  - Natural immunity, including that of the natural killer (NK) cells, is strongly
      influenced by physical exercise, but the physiological significance of the
      reported changes in NK cells after exercise training is as yet unclear. The
      exercise effect is likely mediated by interactions between the central nervous
      and endocrine systems. Chronic activation of endogenous opioid systems augments
      natural cytotoxicity. We have investigated the possible involvement of opioids in
      the exercise-induced enhancement of NK cell function. The pathways by which the
      central nervous system may communicate with the periphery include neuroendocrine
      outflow via the hypothalamic-pituitary-adrenal axis and the autonomic nervous
      system (ANS) through direct nerve fiber connections with cells or the organs of
      the immune system. This review will discuss the role of various neuroendocrine
      factors such as growth hormone, catecholamines and glucocorticoids and the role
      of the ANS, in particular the sympathetic division, in modulating NK cell
      function in response to exercise.

PMID- 10893021
TI  - Exercise and neuroendocrine modulation of macrophage function.
AB  - Like all immune cells, Mphi's cannot simply be viewed as individual cells, but as
      part of a complex network of cells and tissues that communicate in many different
      ways in an attempt to elicit an appropriate host response to immune and other
      challenges. Mphi's are important initial effector cells and are highly regulated
      by other cells (including T and B lymphocytes) and hormones produced by the
      sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis.
      Indeed, it may well be that stressors, including exercise, exert their regulatory
      influence over these cells by activating the SNS, HPA axis, or by influencing
      other tissues or cells. With this in mind, the overall objective of this review
      is to introduce and provide current information regarding the role of
      neuroendocrine factors in mediating exercise-induced changes in macrophage (Mphi)
      function. Under this broad objective this review will: 1) briefly discuss the
      cell biology of the Mphi and its role in host defense, 2) explore the potential
      regulatory influence of selected neuroendocrine hormones (glucocorticoids,
      catecholamines, growth hormone, prolactin, and beta-endorphin) that may
      potentially mediate exercise-induced changes in Mphi function, and 3) describe
      the effects of exercise on the functions of the Mphi.

PMID- 10893022
TI  - Commentary on exercise and neuroendocrine regulation of immune responses.

PMID- 10893023
TI  - Mucosal immunity and respiratory illness in elite athletes.
AB  - This review focuses on studies of immunity in elite athletes and specifically
      addresses the role of mucosal immunity in respiratory illness and associations
      with the intensity, volume and duration of exercise. Investigations of mucosal
      immunity have mostly studied the response of salivary immunoglobulins to
      exercise, although nasopharyngeal secretions and breast milk have also been
      examined. Habitual exercise at an intense level can cause suppression of mucosal
      immune parameters. Salivary IgA and IgM concentrations decline immediately after
      a bout of intense exercise and usually recover within 24 h. Training at an
      intense level can result in a chronic suppression of mucosal immunoglobulin
      levels over many years, and in some endurance sports a decline over a training
      season has been observed. The degree of suppression is associated with the
      intensity of the exercise and the duration or volume of the training. Low levels
      of salivary IgM and IgA, particularly the IgA1 subclass, are associated with an
      increased risk of respiratory illness. Monitoring mucosal immune parameters
      during critical training periods and establishing personal profiles for
      individual athletes may provide an assessment of the risk status of an athlete
      for URTI and allow effective management by the athlete and coach. Despite
      suppression of mucosal immune parameters, elite athletes are capable of normal
      responses to novel oral vaccinations, indicating that mucosal immune mechanisms
      are intact. The mechanisms underlying the mucosal immune suppression are unknown
      but most likely reflect alterations in T-lymphocyte cytokine control mechanisms.

PMID- 10893024
TI  - Elite athlete immunology: importance of nutrition.
AB  - Immunosuppression in athletes involved in heavy training is undoubtedly
      multifactorial in origin. Training and competitive surroundings may increase the
      athlete's exposure to pathogens and provide optimal conditions for pathogen
      transmission. Heavy prolonged exertion is associated with numerous hormonal and
      biochemical changes, many of which potentially have detrimental effects on immune
      function. Furthermore, improper nutrition can compound the negative influence of
      heavy exertion on immunocompetence. An athlete exercising in a carbohydrate
      depleted state experiences larger increases in circulating stress hormones and a
      greater perturbation of several immune function indices. The poor nutritional
      status of some athletes may predispose them to immunosuppression. For example,
      dietary deficiencies of protein and specific micronutrients have long been
      associated with immune dysfunction. An adequate intake of iron, zinc and B
      vitamins is particularly important but the dangers of over-supplementation should
      also be emphasized; many micronutrients given in quantities beyond a certain
      threshold will in fact reduce immune responses and may have other toxic effects
      that are detrimental to health. Although it is impossible to counter the effects
      of all of the factors that contribute to exercise-induced immunosuppression, it
      has been shown to be possible to minimize the effects of many factors. Athletes
      can help themselves by eating a well-balanced diet that includes adequate protein
      and carbohydrate, sufficient to meet their energy requirements. This will ensure
      a more than adequate intake of trace elements without the need for special
      supplements. Consuming carbohydrate (but not glutamine) during exercise
      attenuates rises in stress hormones such as cortisol and appears to limit the
      degree of exercise-induced immunosuppression. By adopting sound nutritional
      practice, reducing other life stresses, maintaining good hygiene, obtaining
      adequate rest and spacing prolonged training sessions and competition as far
      apart as possible, athletes can reduce their risk of infection.

PMID- 10893025
TI  - Training strategies to maintain immunocompetence in athletes.
AB  - Clinical experience and empirical evidence have led to the modeling of exercise
      and training as a form of stress on the immune system. Coaches, athletes, and
      medical personnel are seeking guidelines on ways to reduce the risk of illness
      that compromises training or competitive performance. The immune system is
      influenced by a wide range of physical, environmental, psychological, and
      behavioural factors which, combined with clinical assessment, collectively form
      the basis of the following intervention strategies: 1) training: careful
      management of training volume and intensity, variety to overcome training
      monotony and strain, a periodised approach to increasing loads, and provision of
      adequate rest and recovery periods; 2) environmental: limiting initial exposure
      when training or competing in adverse environmental conditions (heat, humidity,
      altitude, air pollution) and acclimatising where appropriate; 3) psychological:
      teaching athletes self-management and coping skills and monitoring of athletes'
      responses to the psychological and psychosocial stresses of high-level training
      and competition; 4) behavioural: adopting a well-balanced diet with adequate
      intake of macro- and micro-nutrients, limiting transmission of contagious
      illnesses by reducing exposure to common infections, airborne pathogens, and
      physical contact with infected individuals; and 5) clinical considerations:
      medical screening, pathology testing, immunization and prophylaxis, and routine
      management of illness-prone athletes. Future experimental studies are required to
      develop and enhance the effectiveness of these strategies in reducing illness in
      athletes.

PMID- 10893026
TI  - Exercise immunology: future directions for research related to athletes,
      nutrition, and the elderly.
AB  - This article examines three questions related to exercise immunology: 1) Can
      exercise attenuate changes in the immune system related to aging? The few
      research papers available suggest that the answer may be "yes", but exercise
      training may have to be long-term and of sufficient volume to induce changes in
      body weight and fitness before any change in immunity can be expected in old age.
      2) Is the athlete an immunocompromised host? For most athletes, probably not,
      although the answer may be 'yes' during certain periods when the athlete exceeds
      normal training limits or competes in endurance events. Most studies have
      reported that the immune systems of athletes and nonathletes in the resting state
      are more similar than disparate with the exception of natural killer cell
      activity which tends to be elevated in athletes. Infection risk may be more
      related to the acute changes in immunity that occur following heavy exercise, but
      this hypothesis has not been sufficiently studied. 3) Are nutrition supplements
      effective countermeasures to exercise-induced inflammation and immunosuppression?
      Except for carbohydrate, the answer at this time for all other nutrients studied
      is 'no'. While data from the vitamin and mineral studies have been negative, and
      those involving glutamine conflicting, several investigations indicate that
      carbohydrate compared to placebo ingestion is associated with attenuated hormonal
      and immune responses.

PMID- 10893027
TI  - Direct liquid chromatographic enantiomer separation of new fluoroquinolones
      including gemifloxacin.
AB  - The enantiomers of gemifloxacin mesylate (formerly LB20304a), a new
      fluoroquinolone compound with potent in vitro and in vivo antibacterial profile
      were resolved on a commercially available Crownpak CR chiral stationary phase
      (CSP). All of the fluoroquinolones, including gemifloxacin used in this study,
      were well enantioseparated on Crownpak CR(+) column. These results are the first
      reported for the direct separation of the enantiomers of quinolones on chiral
      crown ether coated Crownpak CR CSP. The behavior of chromatographic parameters by
      the change of mobile phase additives for the resolution of gemifloxacin was
      investigated. Also, the effect of structural change of gemifloxacin on chiral
      recognition was described.

PMID- 10893028
TI  - Micelle-mediated extraction for concentrating hydrophobic organic compounds.
AB  - An extraction method based on polymer-induced phase separation of aqueous
      micellar solutions of octyl-beta-D-thioglucoside (OTG) was assessed for
      concentrating hydrophobic analytes. Various hydrophobic compounds such as
      polycyclicaromatic hydrocarbons, alkylbenzenes, alkylphenols, chlorobenzenes,
      chlorophenols, phthalic esters, pesticides, and steroid hormones could be
      efficiently concentrated into a small volume of surfactant-rich phase, while
      hydrophilic matrix components remained in the bulk aqueous phase. The surfactant
      rich phase containing concentrated OTG could be directly introduced into the
      hygro-organic mobile phase of high-performance liquid chromatography with ultra
      violet photometric detection. The application of this method greatly enhanced the
      signal intensity in the chromatogram while reducing the interference of matrix
      components.

PMID- 10893029
TI  - Ion chromatographic determination of inositol in infant formulae and clinical
      products for enteral feeding.
AB  - An ion chromatographic method is described for the determination of inositol in
      infant formula and products for enteral feeding. A two-step procedure for
      hydrolysis and extraction of total inositol has been developed, involving
      alkaline hydrolysis with 3 M potassium hydroxide and enzymatic dephosphorylation.
      Substances having a long chromatographic retention time were removed with an ion
      exchange resin. Inositol was separated on a high-resolution ion-exchange column
      and detected by pulsed amperometric detection. Phytic acid interferes only
      slightly in the analysis. This method can be used for determination of total
      inositol in infant formulae, and enteral feeding products. The analytical method
      gave an average recovery of 94% from infant formula samples spiked with inositol
      and a recovery of 86+/-3% from products spiked with lecithin.

PMID- 10893030
TI  - Speciation of butyl- and phenyltin compounds in sediments using pressurized
      liquid extraction and liquid chromatography-inductively coupled plasma mass
      spectrometry.
AB  - A liquid chromatographic method with inductively coupled plasma mass spectrometry
      is proposed for the speciation of butyl- (monobutyltin, dibutyltin, tributyltin)
      and phenyl- (monophenyltin, diphenyltin, triphenyltin) tin compounds in
      sediments. After evaluation of different additives in the mobile phase, the use
      of 0.075% (w/v) of tropolone and 0.1% (v/v) of triethylamine in a mobile phase of
      methanol-acetic acid-water (72.5:6:21.5) allowed the best chromatographic
      separation of the six compounds. Pressurized liquid extraction (PLE) with a
      methanolic mixture of 0.5 M acetic acid and 0.2% (w/v) of tropolone was suitable
      for the quantitative extraction of butyl- and phenyltin compounds with recovery
      values ranging from 72 to 102%. This analytical approach was compared to
      conventional solvent extraction methods making use of acids and/or organic
      solvent of medium polarity. The main advantages of PLE over conventional solvent
      extraction are: (i) the possibility to extract quantitatively DPhT and MPhT from
      sediments, which could not be done by a solvent extraction approach; (ii) to
      preserve the structural integrity of the organotin compounds; (iii) to reduce the
      extraction time from several hours in case of solvent extraction techniques to
      just 30 min. For spiked sediments, limits of detection ranged from 0.7 to 2 ng/g
      of tin according to the compound. The relative standard deviations were found to
      be between 8 and 15%. The developed analytical procedure was validated using a
      reference material and was applied to various environmental samples.

PMID- 10893031
TI  - Enantioseparation of selected N-tert.-butyloxycarbonyl amino acids in high
      performance liquid chromatography and capillary electrophoresis with a
      teicoplanin chiral selector.
AB  - Enantioseparation of N-tert.-butyloxycarbonyl amino acids (N-t-Boc-Aas) with
      teicoplanin chiral selector was performed in two different separation systems: A
      teicoplanin-based chiral stationary phase (CSP-TE) was used in reversed-phase
      HPLC, and the same chiral selector (CS) was added into a background electrolyte
      (BGE) in HPCE. The enantioselective interaction with the same CSP/CS can be
      influenced by several factors, such as mobile phase/background electrolyte
      composition: the buffer concentration, pH, the CS concentration, the presence of
      organic modifiers. In addition, the charge of the chiral selector related to the
      charge of the analyte and to EOF are important variables in CE. The effect of
      these parameters on enantioselectivity and enantioseparation of selected N-t-Boc
      Aas was studied. The presence of a sufficient concentration (1% solution) of a
      triethylamine acetate buffer in the mobile phase was shown to be essential for
      enantioseparation of these blocked amino acids in HPLC. A certain concentration
      of teicoplanin aggregates (along with teicoplanin molecules) in the BGE is
      required to obtain enantioseparation of N-t-Boc-Aas in HPCE.

PMID- 10893032
TI  - Distribution coefficients of n-alkanes measured on wall-coated capillary columns.
AB  - Distribution coefficients K of n-alkanes were determined in wide ranges of
      temperature and carbon numbers from gas chromatographic retention data measured
      on wall-coated poly(dimethylsiloxane) commercial capillary columns. A discussion
      is centered on how to mitigate the difficulties for an accurate determination of
      K when using weakly retentive columns, as those bearing very high phase ratios or
      short lengths. Particularly, the errors associated with the estimation of the gas
      hold-up and the phase ratio of the column are considered. The chromatographic
      importance for determining K of n-alkanes relies on the fact that these are the
      most commonly applied references for reporting relative thermodynamic parameters
      such as the Kovats Index and the relative retention. A great amount of
      information has been compiled in this form. If K of the reference is known,
      absolute values of distribution coefficients for a myriad of substances are
      readily obtainable. The knowledge of K(T) functions of solutes in wide ranges of
      temperature is a primary necessity in temperature-programmed gas chromatography.
      This knowledge is needed for the prediction of absolute retention times and for
      computing separation optimizations of mixtures containing several critical pairs
      of analytes.

PMID- 10893033
TI  - Comparison of nutshell granular activated carbons to commercial adsorbents for
      the purge-and-trap gas chromatographic analysis of volatile organic compounds.
AB  - Granular activated carbons (GACs) made from agricultural by-products were
      investigated as adsorbents for short path thermal desorption gas chromatographic
      analysis of selected polar and nonpolar organic compounds. GACs made from
      macadamia nut, black walnut and hazelnut shells were compared to four
      commercially available adsorbents, namely, Tenax TA, Carboxen 569, Carbosieve
      SIII and coconut charcoal for their properties in purge-and-trap analysis.
      Adsorption values and breakthrough volumes were calculated for compounds from C3
      and C6-C10. GACs derived from macadamia nut shells were found to adsorb and
      desorb between 80% (benzene) and 277% (ethylbenzene) more acetone (C3), benzene
      (C6), toluene (C7), ethyl- (C8), n-propyl- (C9), or sec.-butylbenzenes (C10)
      purged from water at the 100 ppb level than the commercial adsorbents tested.

PMID- 10893034
TI  - Solid-phase microextraction for determining the distribution of sixteen US
      Environmental Protection Agency polycyclic aromatic hydrocarbons in water
      samples.
AB  - A solid-phase microextraction (SPME) procedure has been developed for the
      determination of 16 US Environmental Protection Agency promulgated polycyclic
      aromatic hydrocarbons (PAHs). Five kinds of SPME fibers were used and compared in
      this study. The extracted sample was analyzed by gas chromatography with flame
      ionization detection or mass spectrometry. Parameters affecting the sorption of
      analyte into the fibers, including sampling time, thickness of the fiber coating,
      and the effect of temperature, have been examined. Moreover, the feasibility of
      headspace SPME with different working temperatures was evaluated. The method was
      also applied to real samples. The 85-microm polyacrylate (PA) and 100-microm
      poly(dimethylsiloxane) (PDMS) fibers were shown to have the highest affinities
      for the selected PAHs. The PA fiber was more suitable than the PDMS fiber for the
      determination of low-ring PAHs while high sensitivity of high-ring PAHs was
      observed when a 100-microm PDMS fiber was used. The method showed good linearity
      between 0.1 and 100 ng/ml with regression coefficients ranging from 0.94 to
      0.999. The reproducibility of the measurements between fibers was found to be
      very good. The precisions of PA and PDMS fibers were from 3 to 24% and from 3 to
      14%, respectively. Headspace SPME is a valid alternative for the determination of
      two- to five-ring PAHs. A working temperature of 60 degrees C provides
      significant enhancement in sensitivity of two- to five-ring PAHs having low vapor
      pressures (>10(-6) mmHg at 25 degrees C) (1 mmHg = 133.3 Pa) and low Henry's
      constants (>10 atm ml/mol) (1 atm = 1.01 x 10(5) Pa).

PMID- 10893035
TI  - Modified capillary electrophoresis system for peptide, protein and double
      stranded DNA analysis.
AB  - The results of high-performance capillary electrophoresis (HPCE) studies of
      peptide, protein and double-stranded DNA separations on a laboratory-made HPCE
      system are presented. Parameters of the HPCE system are given. The new method of
      capillary surface modification by grafting poly(glycidyl methacrylate) is
      described. The problems of HPCE biopolymer analysis connected with the sample
      wall interactions are discussed.

PMID- 10893036
TI  - Optimization of separation and migration behavior of cephalosporins in capillary
      zone electrophoresis.
AB  - The influences of buffer pH, buffer concentration and buffer electrolyte on the
      migration behavior and separation of 12 cephalosporin antibiotics in capillary
      zone electrophoresis using three different types of buffer electrolyte, including
      phosphate, citrate, and 2-(N-morpholino)ethanesulfonate (MES), were investigated.
      The results indicate that, although buffer pH is a crucial parameter, buffer
      concentration also plays an important role in the separation of cephalosporins,
      particularly when cefuroxime and cefazolin, cephalexin and cefaclor, or
      cefotaxime and cephapirin are present as analytes at the same time. The
      electrophoretic mobility of cephalosporins and electroosmotic mobility measured
      in citrate and MES buffers are remarkably different from those measured in
      phosphate buffer. With citrate buffer, optimum buffer concentration is confined
      to a small range (35-40 mM), whereas buffer concentrations up to 300 mM can be
      used with MES buffer. Complete separations of 12 cephalosporins could be
      satisfactorily achieved with these three buffers under various optimum
      conditions. However, the separability of 12 cephalosporins with citrate or MES
      buffer is better than that with phosphate buffer. As a consequence of a greater
      electrophoretic mobility of cephalosporins than the electroosmotic mobility with
      citrate buffer at pH below about 5, some cephalosporins are not detectable. The
      cloudiness of the peak identification and of the magnitudes of the
      electrophoretic mobility of cefotaxime and cefuroxime reported previously are
      clarified. In addition, the pKa values of cephradine, cephalexin, cefaclor, and
      cephapirin attributed to the deprotonation of either an amino group or a
      pyridinium group are reported, and the migration behavior of these cephalosporins
      in the pH range studied is quantitatively described.

PMID- 10893037
TI  - Analysis of polymyxin B sulfate by capillary zone electrophoresis with
      cyclodextrin as additive. Method development and validation.
AB  - A capillary zone electrophoresis method for analysis of polymyxin B sulfate is
      described. In this method, triethanolamine (TEA)-phosphate buffer at pH 2.5 was
      employed to reduce the adsorption of analyte onto the capillary wall. Methyl-beta
      cyclodextrin (M-beta-CD) and 2-propanol (IPA) were found to be necessary for
      selectivity enhancement. In order to optimize the method and to control its
      robustness, a central composite design was performed with four parameters, i.e.
      concentration of M-beta-CD, TEA, IPA and buffer pH. The optimal separation
      conditions were as follows: capillary, 55 cm (50 microm I.D., 47 cm effective
      length); 130 mM TEA-phosphate buffer (pH 2.5) containing 5 mM M-beta-CD and 5%
      IPA; 24 kV (51 microA) applied voltage; column temperature, 20 degrees C.
      Further, linearity and limits of detection quantification were examined. Three
      commercial samples were analyzed quantitatively.

PMID- 10893038
TI  - On-line isotachophoretic sample focusing for loadability enhancement in capillary
      electrochromatography-mass spectrometry.
AB  - The use of isotachophoretic (ITP) sample focusing to improve the detection limits
      for the analysis of charged compounds in capillary electrochromatography (CEC) is
      described. A coupled-column set-up was used with a 220-microm inner diameter
      capillary, in which counterflow ITP focusing was performed, connected via a T
      junction to a 75-microm inner diameter CEC capillary. As is illustrated, the use
      of ITP focusing resulted in a dramatic reduction of the sample concentration
      detection limits. To demonstrate the performance of the ITP-CEC combination,
      several cationic low-molecular mass compounds in a plasma and urine matrix are
      analysed using UV-absorbance and mass spectrometric detection. A linear
      calibration curve was constructed over three decades and detection limits in the
      low nmol/l range were found for academic samples, using UV-absorbance detection.

PMID- 10893039
TI  - Capillary electrophoretic determination of thiosulfate and its oxidation
      products.
AB  - Capillary electrophoresis (CE) was developed for the rapid and simple
      determination of thiosulfate and its oxidation products such as common
      polythionates, sulfite and sulfate. Direct and indirect UV detection techniques
      were investigated. The optimized separations of UV absorbing S2O3(2-), S4O6(2-),
      S5O6(2-) and S6O6(2-) anions were carried out in 5 mmol l(-1) (NH4)2SO4, 5 mmol
      l(-1) KH2PO4 electrolyte at pH 5.0, with direct UV detection at 214 nm. All
      analytes were well resolved in less than 4 min. Analysis of S2O3(2-), S4O6(2-),
      SO4(2-) and SO3(2-) ions can be performed in 5 mmol l(-1) H2CrO4, 1 mmol l(-1)
      hexamethonium hydroxide electrolyte neutralized with triethanolamine to pH 8.0,
      using indirect UV detection at 254 nm. However, the detection sensitivity for
      tetrathionate was poor. Other polythionates can not be detected at all because of
      their high absorbance even at 254 nm. The developed CE method was applied for the
      monitoring of sulfur species in spent fixing solutions during the electrolytic
      oxidation.

PMID- 10893040
TI  - Separation of anions by ion chromatography-capillary electrophoresis.
AB  - Capillary electrophoresis (CE) with a water-soluble ion-exchange polymer in the
      background electrolyte is very efficient for the separation of organic and
      inorganic anions because the ion-exchange selectivity, as well as differences in
      electrophoretic mobility, can be used for separating sample ions.
      Poly(diallyldimethylammonium chloride) (PDDAC) was employed for this purpose. A
      very stable electroosmotic flow was obtained between pH 2.3 and 8.5 due to the
      strong adsorption of PDDAC onto the capillary wall. The effect of ion exchange on
      the migration of sample anions and their separation was controlled by varying the
      concentration of PDDAC, the concentration and the type of salt used in the CE
      background electrolyte. Addition of organic solvent (e.g., acetonitrile) could
      also modify the sample migration and the separation. Baseline separations were
      obtained for anions with very similar mobilities, such as bromide and iodide,
      naphthalenesulfonates, and bi- and tricarboxylic acids. Typical separation
      efficiencies were between 195,000 and 429,000 theoretical plates per meter. Ten
      replicate separations gave an average RSD of 1.0% for migration times of the
      sample anions studied. Excellent separations were obtained for a variety of
      samples, including a separation of 17 inorganic and organic anions in less than 6
      min.

PMID- 10893041
TI  - Endothelium function in sepsis.
AB  - Endothelial cells can be the prime target for an infection and infected
      endothelial cells may serve as an initiating system for a systemic response as
      these cells are able to secrete many mediators known to be of paramount
      importance. Endothelial cell functions in turn are regulated by these circulating
      mediators. Cellular interactions with leukocytes revealed protective and
      destructive functions. Single cell and animal studies indicate that endothelial
      permeability is increased and apart from clinical obvious edema formation in
      septic patients, the endothelial component remains unknown. Endothelial
      coagulation activation has been shown in vitro, however human data supporting an
      endothelial procoagulatory state are lacking. Defects in endothelium dependent
      vasoregulation in animal models are well known and again human studies are
      largely missing. An imbalanced production of reactive oxygen species including
      nitric oxide has been found to be involved in all endothelial functions and may
      provide a common link which at present can be supported only in animal studies.

PMID- 10893042
TI  - Immunology of DNA vaccines: CpG motifs and antigen presentation.
AB  - DNA vaccines elicit high levels of specific cytotoxic T lymphocytes and antibody
      production in numerous animal models. However, the specific immunological events
      which lead to this effective immune response remain unclear. Presentation of DNA
      encoded antigens is particularly intriguing as there is now evidence to suggest
      that this occurs via both endogenous intracellular and cross-presentation.
      Further, it has been observed that many plasmid DNA vectors used in DNA
      vaccination contain CpG motifs--sequences of bacterial DNA which induce pro
      inflammatory cytokines in various cells--and which thus provide a novel adjuvant
      for injected antigens. In this review we will discuss the effects these bacterial
      DNA sequences have on cells of the immune system, the immune response generated
      after DNA vaccination and the mechanisms by which DNA-encoded antigens are likely
      to be presented.

PMID- 10893043
TI  - Distinct ability to accumulate eosinophils during the inflammatory cellular
      response to M. bovis BCG in the mouse pleural cavity.
AB  - OBJECTIVE AND DESIGN: The host response to Mycobacteria focuses on the
      development of cell-mediated immunity and granuloma formation. Here, we
      investigated the onset of cellular responses to mycobacteria in murine pleurisy.
      MATERIAL: Distinct mouse strains previously described as Bcg susceptible or
      resistant were inoculated intrathoracically with different doses of live M. bovis
      BCG. METHODS: At various time intervals, cells harvested from the inflammatory
      site were identified and ultra-structurally analysed. RESULTS: BCG-induced
      pleurisy had two peaks of cellular influx at 1 and 15 days after infection. At
      the first half hour, macrophages were found to be heavily infected. Neutrophil
      arrival started after 2 h of infection and peaked at 4 h. At this time,
      neutrophils were found ingesting mycobacteria exclusively with a high infecting
      dose. BCG was potently more eosinophilotactic in Bcg susceptible mice than in the
      resistant ones and to other well known eosinophilia inducers: IL-5, PAF-acether
      or LPS. CONCLUSIONS: Mycobacterial load and mouse susceptibility seem to
      determine the early granulocyte dynamics in the lesion.

PMID- 10893044
TI  - Nutritional supplementation with copper in the rat. I. Effects on adjuvant
      arthritis development and on some in vivo- and ex vivo-markers of blood
      neutrophils.
AB  - OBJECTIVE AND DESIGN: The aims of the work were: 1) to confirm the preliminarily
      observed anti-arthritic potential of a 200 ppm copper-supplemented diet in the
      rat: 2) to study the impact of the nutritional treatment and of the experimental
      pathology on neutrophil activity. ANIMALS AND CELLS: Two hundred female Sprague
      Dawley rats were used. Polymorphonuclear leukocytes were isolated from these
      animals for the ex vivo studies. TREATMENT: Control-rats were maintained on a
      standard diet containing 5 ppm of copper. Supplemented-rats were kept on a diet
      containing 200 ppm of the metal. METHODS: Mycobacterium butyricum-induced
      arthritis was studied. Flame atomic absorption spectroscopy was used to assess
      copper and zinc levels. The "microplate-assay" technique was used to determine
      serum lysozyme concentration (lysis of Micrococcus lysodeikticus cell walls), as
      well as neutrophil O2- generation (superoxide dismutase-inhibitable reduction of
      ferricytochrome-c), and adhesion (activity of the membrane enzyme acid
      phosphatase). The results were statistically evaluated by the Student's t test.
      RESULTS: The nutritional copper-supplementation: 1) significantly inhibited the
      adjuvant-arthritis development (33% +/- 5, P<0.01); 2) did not modify lysozyme
      secretion or superoxide production; 3) significantly decreased the percentage of
      cell adhesion by an average of 41% +/- 19 (P<0.01). CONCLUSIONS: The copper
      supplemented diet has an anti-arthritic effect which may be also primed by the
      effect of copper on the expression of the neutrophil cell-adhesion molecules.

PMID- 10893045
TI  - Differential activation of platelets from normal and allergic ponies by PAF and
      ADP.
AB  - OBJECTIVE AND DESIGN: Altered platelet responsiveness has been demonstrated in
      human atopic dermatitis. This study has compared the in vitro function of
      platelets from normal ponies and those with the allergic skin disease, sweet
      itch. SUBJECTS: Ponies with a clinical history of sweet itch and normal ponies
      were used as blood donors. METHODS: PAF and ADP-induced platelet aggregation was
      measured and TxB2 production quantitated at the time of maximal aggregation; 12
      HETE was additionally measured in some samples. Agonist-induced release of 3[H]5
      HT was also studied. RESULTS: Although both PAF and ADP caused equine platelet
      aggregation, only PAF stimulated eicosanoid and 5-HT release. There were no
      differences between the responses of platelets from allergic and normal ponies to
      PAF or ADP (analysis of variance). CONCLUSIONS: There is no evidence of altered
      platelet responsiveness in ponies with sweet itch. The profile of responses to
      PAF and ADP suggest differential activation of intracellular signalling pathways
      in equine platelets.

PMID- 10893046
TI  - L-Histidine decarboxylase protein and activity in rat brain microvascular
      endothelial cells.
AB  - OBJECTIVE AND DESIGN: L-Histidine decarboxylase (HDC) is the primary enzyme
      regulating histamine biosynthesis. This study was carried out to examine whether
      the cultured rat brain microvascular endothelial cells (BMEC), which constitute
      the blood-brain barrier (BBB), have the ability to form histamine, and whether
      HDC mRNA is expressed in rat BMEC. MATERIAL: Male, 3-week-old Wistar rats were
      used. For in vitro studies, rat BMEC were isolated from rat brains, and
      subculture cells were grown on collagen-coated culture flask and slide. METHODS:
      HDC assay, immunofluorescence analysis and expression of HDC mRNA by RT-PCR were
      performed in rat BMEC. RESULTS: The HDC activity of the BMEC was estimated to be
      0.14 +/- 0.05 p mol/min/mg protein. This activity was completely inhibited by (S)
      alpha-fluoromethylhistidine, a specific inhibitor of HDC. Using a polyclonal anti
      HDC antibody and immunofluorescence microscopy, we confirmed the presence of HDC
      protein in rat BMEC. RT-PCR also showed the expression of HDC mRNA in rat BMEC.
      CONCLUSIONS: L-Histidine uptaken by rat BMEC was shown to be converted to
      histamine, suggesting that HDC plays an important role in BBB.

PMID- 10893047
TI  - Up-regulation of human eosinophil leukotriene C4 generation through contact with
      bronchial epithelial cells.
AB  - OBJECTIVE AND DESIGN: We studied the effect of contact with bronchial epithelial
      cells on the functional activity of human eosinophils, measured as the production
      of a bronchoconstrictor lipid mediator, leukotriene C4 (LTC4) to determine the
      role of cell-cell interaction in activation of airway eosinophils. MATERIALS AND
      METHODS: Eosinophils were isolated from peripheral blood of atopic donors.
      Epithelial cells were obtained from the bronchi of surgically resected lung lobes
      and cultured to confluence on collagen-coated plates. Eosinophils were stimulated
      with platelet activating factor (PAF) or serum opsonized zymosan (SOZ) after
      incubation with or without epithelial cells. Leukotriene C4 (LTC4) was assayed in
      supernatants by enzyme immunoassay. RESULTS: Bronchial epithelial cells did not
      produce LTC4 in response to PAF or SOZ. Eosinophils pre-incubated in collagen
      coated plates for 1 h produced LTC4 in response to both PAF (130 +/- 53
      fmol/10(6) eosinophils at 10 micromol/l PAF, 5 min) and SOZ (1,900 +/- 550
      fmol/10(6) eosinophils at 2 mg/ml SOZ, 15 min). Eosinophils co-incubated with
      bronchial epithelial cells for 1 h produced significantly higher quantities of
      LTC4 in response to both PAF (310 +/- 94 fmol/10(6) eosinophils; P<0.01) and SOZ
      (5,500 +/- 1,500 fmol/10(6) eosinophils; P<0.001). Ligation of the common beta2
      integrin subunit (CD18) with a monoclonal antibody inhibited PAF-stimulated and
      augmented SOZ-stimulated LTC4 generation by eosinophils alone but had marginal
      effects on the epithelium-dependent up-regulation. CONCLUSIONS: Contact with
      bronchial epithelial cells up-regulates the responsiveness of human eosinophils,
      a finding that has significant implications in the pathology of asthma.

PMID- 10893048
TI  - Phenotypic variation in mast cell responsiveness to the inhibitory action of
      nitric oxide.
AB  - OBJECTIVE AND DESIGN: The aim of this study was to investigate the possible
      phenotypic variations between mast cells in terms of their responsiveness to the
      inhibitory actions of nitric oxide. MATERIALS: Unfractionated mouse peritoneal
      cells, purified rat peritoneal mast cells, mouse bone marrow-derived mast cells
      of the C1.MC/C57.1 line (cultured mouse mast cells, CMMC) and rat basophilic
      leukemia cells of the RBL-2H3 line were used. METHODS: Mast cells were cultured
      with interferon-gamma (IFN-gamma)-stimulated mouse peritoneal cells as a source
      of nitric oxide, or with the nitric oxide donor S-nitrosoglutathione (SNOG).
      After 24 h culture, the mast cells were challenged with anti-IgE, antigen, or
      calcium ionophore A23187, and degranulation measured as release of [3H]serotonin.
      RESULTS: Addition of IFN-gamma to mouse peritoneal cells led to nitric oxide
      synthesis and this was associated with decreased IgE-mediated mast cell
      degranulation. IFN-gamma did not induce nitric oxide production by CMMC and
      degranulation of CMMC was not inhibited by nitric oxide generated by co-cultured
      IFN-gamma-activated peritoneal cells. The nitric oxide donor SNOG inhibited
      degranulation of purified rat peritoneal mast cells, but not RBL-2H3 cells,
      stimulated by either IgE cross-linking or calcium ionophore. CONCLUSIONS: The
      inhibitory effects of nitric oxide on mast cell degranulation are variable and
      selective for phenotype. Such phenotypic differences may reflect important
      variations in regulation of mast cell function.

PMID- 10893049
TI  - From opiate pharmacology to opioid peptide physiology.
AB  - This is a personal account of how studies of the pharmacology of opiates led to
      the discovery of a family of endogenous opioid peptides, also called endorphins.
      The unique pharmacological activity profile of opiates has an endogenous
      counterpart in the enkephalins and beta-endorphin, peptides which also are
      powerful analgesics and euphorigenic agents. The enkephalins not only act on the
      classic morphine (mu-) receptor but also on the delta-receptor, which often co
      exists with mu-receptors and mediates pain relief. Other members of the opioid
      peptide family are the dynorphins, acting on the kappa-receptor earlier defined
      as precipitating unpleasant central nervous system (CNS) side effects in
      screening for opiate activity, A related peptide, nociceptin is not an opioid and
      acts on the separate NOR-receptor. Both dynorphins and nociceptin have modulatory
      effects on several CNS functions, including memory acquisition, stress and
      movement. In conclusion, a natural product, morphine and a large number of
      synthetic organic molecules, useful as drugs, have been found to probe a
      previously unknown physiologic system. This is a unique development not only in
      the neuropeptide field, but in physiology in general.

PMID- 10893050
TI  - Impact of different inspiratory flow patterns on arterial C02-tension.
AB  - Ventilation with decelerating inspiratory flow is known to reduce the dead space
      fraction and to decrease PaCO2. Constant inspiratory flow with an end-inspiratory
      pause (EIP) is also known to increase the removal of CO2. The aim of the study
      was to elucidate the effect of the pause/no-flow period while both the pattern
      and rate of inspiratory flow was unchanged, and when the lung was ventilated with
      sufficient PEEP to prevent end-expiratory collapse. Surfactant depleted piglets
      were assigned to decelerating or constant inspiratory flow with 24 breaths per
      minute (bpm) or 12 bpm, or to constant flow, without and with an end-inspiratory
      pause of 25%. By adding an EIP the total time without active inspiratory flow of
      the respiratory cycle was kept unchanged. Gas exchange, airway pressures,
      functional residual capacity (using sulfurhexafluoride) and haemodynamics (thermo
      dye indicator dilution technique) were measured. Irrespective of ventilatory
      frequency, PaCO2 was lower and serial dead space reduced with decelerating flow,
      compared with constant inspiratory flow. With an end-inspiratory pause added to
      constant inspiratory flow, serial dead space was reduced but did not decrease
      PaCO2. The results of this study corroborate the assumption that total time
      without active inspiratory flow is important for arterial CO2-tension.

PMID- 10893051
TI  - Morphologic conversion of Helicobacter pylori from spiral to coccoid form.
      Scanning (SEM) and transmission electron microscopy (TEM) suggest viability.
AB  - Helicobacter pylori is a pathogen associated with type B gastritis, peptic ulcer
      disease, gastric atrophy, and stomach cancer. H. pylori exists in two
      morphological forms, spirals and coccoids. The latter has been described as
      viable but non-cultivable. The role of the coccoid form in the pathogenesis of
      gastric disease is disputed. Some authors consider the coccoid form to be a
      degenerative or dead form of H. pylori, while others consider it a resting but
      still metabolically active form. This study reports the conversion from spiral to
      coccoid form ultrastructurally. Dense material is accumulated in the periplasmic
      space, the spiral bacteria bend and the outer membrane is separated from the
      inner cell wall layer. Remodeling of inner structures takes place, ending in the
      coccoid form of the bacteria with preserved light polyphosphate areas. Reduction
      of surface takes place by production of surface membrane vesicles, which later
      are squeezed off. The finding of preserved subcellular structures and intact
      double membranes in combination with degenerative forms suggests that some of the
      coccoids are viable. Scanning electron microscopy (SEM) demonstrates coccoid form
      of bacteria with slightly ruffled surfaces but no spiral forms.

PMID- 10893052
TI  - The effect of smoking on glucose homeostasis and fetal growth in pregnant women.
AB  - OBJECTIVE: To examine the relationship between maternal blood glucose levels,
      cigarette smoking in pregnancy and fetal growth. DESIGN: A prospective study of
      healthy parous women from early pregnancy and their infants. SETTING: Three
      Scandinavian university hospitals covering all deliveries from well defined
      geographical areas. SUBJECTS: Study groups of non-smoking (150), light smoking
      (131) and heavily smoking mothers (218), para 1 and 2 and with > 37 weeks of
      gestational length. MAIN OUTCOME MEASURES: Oral glucose tolerance test performed
      in pregnancy week 37, glycated hemoglobin measured the 3rd day post partum and
      neonatal anthropometric parameters including skinfold measurements. RESULTS:
      Among heavily smoking mothers 12.4% displayed a 2-hour glucose value in the range
      of gestational diabetes (> 8.5 mmol/l) compared to 9.2% among light smokers and
      6.0% among nonsmokers (p < 0.05). Heavily smoking mothers also had significantly
      (p < 0.05) higher glycated hemoglobin compared to nonsmokers, 5.01 v.s. 4.86.
      These changes in glucose parameters in smokers were not associated with higher
      birthweights. CONCLUSIONS: Smoking in pregnancy affects parameters of glucose
      homeostasis in the direction of gestational diabetes. The retarding effect of
      smoking on fetal growth abolished any expected growth stimulation from the higher
      blood glucose levels seen in the smokers.

PMID- 10893053
TI  - Very early discharge from hospital after normal deliveries.
AB  - The aim of the present study was to investigate, in a descriptive study, how
      healthy women experienced early discharge from hospital, 6-12 hours, after normal
      deliveries. Expecting couples were prepared for early discharge during pregnancy.
      The women delivered at the University Hospital in Uppsala. All infants had two
      obligatory medical examinations, one before leaving the hospital and one for
      metabolic screening after four or five days. Both mothers and infants received
      postpartum care at home by midwives. One hundred and three women participated and
      answered a questionnaire four to five days after delivery. Twenty of the women
      were additionally interviewed by telephone four months after delivery. The
      average length of stay at the hospital after delivery was 8 hours. The families
      had, on average, 1.9 visits at home. All women considered that they had received
      sufficient care and advice from the midwives, although 40 percent felt
      uncertainty about something in the postpartum period. Questions frequently raised
      concerned breast-feeding. Two infants were readmitted to hospital due to mild
      neonatal hyperbilirubinemia. All but three women wanted to repeat very early
      discharge after a future uncomplicated delivery. Ninety-five percent of the women
      were still breast-feeding after four months. We conclude, that antenatal
      preparation and a well-organised, adequate postpartum home-care is of the
      greatest importance, to establish safe early discharge after uncomplicated
      deliveries. This concept of early discharge from hospital, with midwifery home
      care provided, is safe and appreciated by the new parents.

PMID- 10893054
TI  - Measurement accuracy of aluminium content in bone.
AB  - The aluminium content in bone has been related in several ways: to the weight of
      wet bone, to the weight of dry bone, to the weight of bone-ash and to the calcium
      content of bone. We determined the accuracy and precision of measurement (using
      an inductively coupled mass-spectrometer) in 30 bone samples taken from one
      patient. The coefficient of variation of the aluminium/weight-quotient was 12.4
      per cent for wet bone, 4.7 for dry bone and 5.0 for bone ash; and the coefficient
      of variation of the aluminium/calcium-weight-quotient was 7.5 per cent. Thus, the
      aluminium content in bone seems to be best related to the weight of dry bone.

PMID- 10893055
TI  - Cerebrovascular effects of the TRH analogues pGlu-3-methyl-His-Pro amide and pGlu
      Glu-Pro amide: a comparison with TRH.
AB  - The goal of the study was to assess whether TRH analogues possess cerebrovascular
      effects similar to the native peptide. The neuropeptide thyrotropin releasing
      hormone (TRH) elicits cerebrovasodilation in several species under various
      conditions. The laser-Doppler method was employed to study the effects of TRH and
      the analogues pGlu-3-methyl-His-Pro amid (M-TRH) and pGlu-Glu-Pro amide.
      Intravenous (i.v.) injection of 300 microg kg(-1) of TRH elicited
      cerebrovasodilation and a 62% increase in blood flow within 1 minute. M-TRH, in a
      dose of 300 microg kg(-1) i.v., elicited a 80% increase in cerebral blood flow.
      Even a minute dose of M-TRH (625 ng kg(-1)) caused an increase in cerebral blood
      flow. No clear difference in effects on the cerebral blood flow was observed
      between spontaneously and mechanically ventilated animals, pGlu-Glu-Pro amide had
      no cerebrovascular effect.

PMID- 10893056
TI  - Ultrasound contrast enhancing agents in neurosonology: principles, methods,
      future possibilities.
AB  - OBJECTIVES: Ultrasound of the brain supplying arteries is a standard diagnostic
      procedure in patients with suspected and definite acute and chronic
      cerebrovascular occlusive disease. Anatomical and pathological limitations led to
      the development of echocontrast agents which are able to survive pulmonary and
      capillary transit and improve the echogenicity of the flowing blood. MATERIAL AND
      METHODS: This article reviews present and future applications of echocontrast
      agents in conjunction with personal experiences. RESULTS: Currently, echocontrast
      is used for the differentiation of internal carotid artery occlusion and
      pseudoocclusion, better delineation of the maximal narrowing in high-grade
      stenoses, and better visualization of the extracranial vertebral artery and its
      collaterals. Transcranial applications include the insufficient foraminal or
      temporal window, assessment of arteriovenous malformations, thrombosis of
      cerebral veins and sinuses, and intracranial aneurysms. The use of echocontrast
      can have direct diagnostic and therapeutic consequences. Harmonic imaging,
      perfusion imaging, stimulated acoustic emission, and drug delivery are possible
      future domains of the technique. DISCUSSION: Besides the support of conventional
      neurovascular ultrasound in poor examination conditions due to the patients'
      anatomy or pathology, echocontrast agents may allow for novel applications in the
      diagnosis and treatment of cerebrovascular patients.

PMID- 10893057
TI  - Multi-variate analysis predicts clinical outcome 30 days after middle cerebral
      artery infarction.
AB  - BACKGROUND AND PURPOSE: To evaluate the functional prognostic value of proton
      magnetic resonance spectroscopy performed within the 5 days of an infarction of
      the middle cerebral artery territory, compared with previously demonstrated
      prognostic factors. METHODS: Proton magnetic resonance spectroscopy was performed
      on 77 consecutive non-comatosed patients during the acute stage of middle
      cerebral artery infarction. The functional status was determined for each patient
      via the Orgogozo score. Proton magnetic resonance spectroscopic data were
      acquired in the infarction and in contra-lateral normal tissue and the results
      were expressed as metabolite ratios. Correlations were evaluated between the
      Orgogozo score at day 1 and day 30, the age, the sex, the volume of the
      infarction, and the metabolic ratios. RESULTS: In a monovariate analysis, the
      decrease of the NAA/choline ratio was correlated with a low Orgogozo score at
      days 1 and 30 (P<0.05) and with a large infarction (P<0.05). A stepwise analysis
      showed a significant relationship between the Orgogozo score at day 30 and the
      Orgogozo score at day 1, the sex, the volume of infarction, and the NAA/Cho ratio
      within the infarction. CONCLUSIONS: Our work demonstrates that a good clinical
      outcome at day 30 depends on a good initial clinical score at day 1, a small
      volume of infarction, a small decrease of NAA/Cho, and being of the female
      gender.

PMID- 10893059
TI  - Carotid stents are not a source of microemboli late after deployment.
AB  - OBJECTIVES: To evaluate the presence of microembolic signals (MES) in the middle
      cerebral artery distal to a stented carotid artery late after stent deployment.
      MES may be a signal of thrombus formation at the stent level. PATIENTS AND
      METHODS: Two patient groups were studied with transcranial Doppler at different
      intervals after deployment of Palmaz stents or Wallstents for stenosis of the
      internal or common carotid artery. Group 1: from 6 to 12 months after stent
      deployment; Group 2: > 12 months after stenting. RESULTS: One out of 19 patients
      in Group 1 showed MES (5.0%); however, this patient also had two mechanical heart
      valves. None out of 17 patients in Group 2 had MES. CONCLUSIONS: Carotid stents
      seem to have a very low emboligenic potential after the early post-deployment
      period. This is a reassuring message for present and future patients harboring
      such stents.

PMID- 10893058
TI  - A metabolic threshold of irreversible ischemia demonstrated by PET in a middle
      cerebral artery occlusion-reperfusion primate model.
AB  - OBJECTIVE: to evaluate the predictive value of measurements of regional cerebral
      blood flow (CBF), oxygen metabolism (CMRO2) and oxygen extraction ratio (OER) for
      assessment of the fate of ischemic brain tissue. MATERIALS AND METHODS:
      Sequential PET measurements were performed during middle cerebral artery
      occlusion (MCAO; 2 h) and 12-24 h (mean 18 h) of reperfusion in a primate model
      (Macaca mulatta, n = 8). A penumbra region was delineated on the MCAO PET image
      (OER > 125% and CMRO2> or = 45% of the values observed in the contralateral
      hemisphere, respectively) and an infarction region was delineated on the last PET
      image (CMRO2 <45% of the values observed in the contralateral hemisphere). The
      penumbra regions delineated during MCAO and the infarction regions delineated at
      the final PET, were copied on to the images from all other PET sessions for
      measurements of CBF, CMRO2 and OER. Ratios were calculated by dividing the mean
      values obtained by the values of the corresponding contralateral region. RESULTS:
      Histopathology verified the adequacy of the criteria applied in the last PET for
      delineation of the infarction region. The penumbra region and infarction region
      were separated in all cases, except in two cases where a minimal overlap was
      seen. CBF and OER showed considerable variation over time and there was no
      consistent difference between the penumbra and infarction regions. CMRO2 showed a
      more stable pattern and the difference between penumbra and infarction regions
      was maintained from the time of MCAO throughout the entire reperfusion phase.
      With CMRO2 as predictor, all 50 observations could be correctly predicted as
      penumbra or infarction when using an optimal threshold ratio value estimated to
      be in the interval of 61% to 69% of the corresponding contralateral region. CBF
      and OER proved to have low power as predictors. CONCLUSIONS: The results indicate
      that CMRO2 is the best predictor of reversible or irreversible brain damage and
      the critical metabolic threshold level appears to be a reduction of oxygen
      metabolism to between 61% and 69% of the corresponding contralateral region.

PMID- 10893060
TI  - Screening for thrombophilic risk factors among 25 German patients with cerebral
      venous thrombosis.
AB  - OBJECTIVES: In this study the frequency of inherited thrombophilic risk factors
      in a population of German CVT patients and their influence on clinical outcome
      were evaluated. MATERIAL AND METHODS: Twenty-five patients (age 37.1 +/- 16.3
      years) with CVT were screened for inherited coagulation disorders. All
      participants received a full clinical follow-up (mean follow-up period 4.8 +/-
      6.4 years). RESULTS: Inherited thrombophilic risk factors were identified in 9
      (36%) of the 25 patients studied. Four were found positive for the heterozygous
      factor V Leiden mutation, 2 were heterozygous carriers of the prothrombin-G20210A
      polymorphism. APC resistance proved to be a reliable screening method for factor
      V Leiden mutation, whereas genetic evaluation for protein S and C deficiencies
      failed to demonstrate any mutations despite the identification of 1 patient with
      a protein C and protein S deficiency each. One patient suffered from a familial
      plasminogen deficiency. These 9 patients had a less favorable outcome (P < 0.05).
      CONCLUSION: Our results demonstrate that screening for inherited thrombophilia
      should be an integral part in the diagnostic work up of CVT patients. Patients
      with inherited coagulopathies tended to have a less favorable outcome,
      corroborating recommendations for a longer period of oral anticoagulation.

PMID- 10893061
TI  - Gender differences in Parkinson's disease symptom profile.
AB  - Gender symptom differences were studied in 948 subjects with Parkinson's disease
      (PD) using a questionnaire covering the most common symptoms associated with PD
      at debut (SP-1) and at present (SP-2). The symptoms most frequently reported by
      both genders were: tremor, fumblingness, writing problems, rigidity and fatigue.
      At SP-1 females reported neck-pain and low back pain more frequently than males.
      At SP-2 subjects reported an increased number of symptoms. The following symptoms
      were more frequent among males than females: writing difficulties, fumblingness,
      gait problems, speech problems, increased flow of saliva, lack of initiative.
      Sleep problems were common in both sexes with inability to turn in bed and calf
      muscle cramps in a high percentage. A majority of female subjects find their
      symptoms (e.g. depression) constantly distressing. Although depression is not one
      of primary reported symptoms (36%) attention is called for, due to the problem
      with compliance to treatment regimes. About 30% do not report having tremor and
      rigidity. This study indicates the usefulness of a symptom profile instrument
      capable of capturing the many symptoms involved in PD. Such an instrument could
      be used to detect apparent mistakes in medication and thereby increase the
      function and quality of life for the individual.

PMID- 10893062
TI  - Severe episodic headache as the sole presenting ictal event in patients with a
      solitary cysticercus granuloma.
AB  - OBJECTIVES: Most patients with a solitary cysticercus granuloma present with
      seizures and severe episodic headache as the sole presenting symptom is rare in
      these patients. We report the clinical features, evolution and outcome of the
      disease in patients with a solitary cysticercus granuloma who had severe headache
      alone without seizures as the sole presenting event. MATERIAL AND METHODS: This
      was a prospective study which included all patients who presented with severe
      episodic headache alone and had a diagnosis of a solitary cysticercus granuloma
      based on CT imaging and follow-up and were managed in our department between June
      1, 1991 and May 31, 1998. RESULTS: Out of nearly 550 patients diagnosed to have a
      solitary cysticercus granuloma during the period of the study, 15 patients (2.5%)
      presented with severe episodic headache alone. While 9 patients had 1 episode of
      headache, 6 patients had 2 to 5 episodes. Patients were managed with conservative
      symptomatic therapy (13 patients) and albendazole therapy (2 patients). Follow-up
      scans showed complete or partial resolution of the granuloma in 8 patients and a
      lesion of the same size in 4 patients. None of the patients with complete
      resolution of the granuloma reported further episodes of headache. CONCLUSIONS:
      It is important to recognize this presentation of a solitary cysticercus
      granuloma as it could be confused clinically with other acute central nervous
      system illnesses such as subarachnoid haemorrhage and meningitis. In regions
      endemic for cysticercosis a contrast enhanced CT scan of the brain should be
      performed in patients presenting with sudden onset of severe headache when a
      plain scan does not reveal intracranial haemorrhage as only a contrast enhanced
      scan will reveal the granuloma.

PMID- 10893063
TI  - Increased cystatin C immunoreactivity in the skin in amyotrophic lateral
      sclerosis.
AB  - OBJECTIVES: Several abnormalities of skin have been described in patients with
      amyotrophic lateral sclerosis (ALS). Bunina bodies, which are small eosinophilic
      intraneuronal inclusions in the remaining lower motor neurons in ALS, are the
      only pathologically specific hallmark of ALS. It has been demonstrated that
      Bunina bodies were positive for anti-cystatin C serum. However, cystatin C in the
      skin of ALS has not been investigated. MATERIAL AND METHODS: We studied cystatin
      C immunoreactivity of skin in ALS patients, and the results were compared with
      those of control subjects. RESULTS: The epidermis of ALS was
      immunohistochemically strongly positive for cystatin C as compared with that of
      controls. The optical density of cystatin C immunostaining reactivity in ALS
      patients was significantly higher than in controls, and was significantly
      increased with duration of illness. CONCLUSION: These data suggest that a
      metabolic alteration of cystatin C may take place in the skin of ALS and the
      increased cystatin C in skin is likely to be related to the disease process in
      ALS.

PMID- 10893064
TI  - Is monochorionic twinning a risk factor for focal cortical dysgenesis?
AB  - OBJECTIVES: Various genetic and acquired factors have been proposed as being
      etiologically important in cortical dysgenesis. It has been suggested that fetal,
      developmental abnormalities may be induced by transient, circulatory instability
      in monochorionic twinning due to feto-fetal transfusions. We report the
      discordant occurrence of a malformation of cortical development in monozygotic,
      monochorionic twins, and discuss the findings and possible pathogenetic
      mechanisms. MATERIAL AND METHODS: The twins were females, 30 years of age, one of
      them suffering from uncontrolled localization-related epilepsy. Neurological
      deficits or mental retardation were not present. Genetic analysis, brain MRI, and
      a neuropsychological test battery were carried out. RESULTS: DNA analysis
      verified monozygocity. MRI showed a unilateral grey matter heterotopion and a
      contralateral temporal arachnoid cyst in the affected twin. Neuro-psychological
      assessment revealed no corresponding focal cognitive deficits, but an overall
      slightly lowered performance in the affected twin. CONCLUSION: Discordant
      affection of focal, cortical dysgenesis in monozygotic twins creates a particular
      opportunity to assess the consequences of such a disorder. The fact that only a
      mild generalized influence on cognitive functioning was demonstrated in this
      case, is possibly due to the plasticity of the fetal brain. According to current,
      obstetrical literature, the unique embryology of monochorionic twinning may
      predispose to vascular events in early fetal life. As ultrasound studies now
      indicate that a large proportion of pregnancies start out as twin products, we
      hypothesize that the "vanishing twin" syndrome and its potential hemodynamic
      hazard to the surviving fetus may be an etiological factor in malformations of
      cortical development, even in singletons.

PMID- 10893065
TI  - Membranous lipodystrophy presenting with palilalia: a PET study of cerebral
      glucose metabolism.
AB  - A case of membranous lipodystrophy (Nasu-Hakola disease; NHD) associated with
      palilalia was reported. A 38-year-old Japanese woman developed walking difficulty
      in her twenties. At age 35 she manifested neuropsychiatric symptoms characterized
      by euphoria, palilalia and dementia. A bone marrow biopsy showed periodic acid
      Schiff-positive membranous cystic lesions in the adipose tissue. Positron
      emission tomography with (18F)-2-fluoro-2-deoxy-D-glucose disclosed that regional
      cerebral glucose metabolism was decreased in the bilateral frontal white matter
      with mild hypometabolism in the thalamus and basal ganglia; all predominantly on
      the right. Taken together with the previous postmortem findings, it is postulated
      that frontal lobe hypofunction, predominantly in the right hemisphere, produced
      the unique neuropsychiatric symptoms in this patient.

PMID- 10893066
TI  - Recessively inherited spastic paraplegia associated with ataxia, congenital
      cataracts, thin corpus callosum and axonal neuropathy.
AB  - We investigated a consanguineous Japanese family with a complicated form of
      familial spastic paraplegia (FSP). Three siblings were affected, probably by
      autosomal recessive inheritance. All showed ataxia, subnormal mentality,
      congenital cataracts, and slight cerebellar atrophy on CT scans. Spastic
      paraplegia was predominant in 2 siblings, while ataxia was more marked in the
      other. Slight but definite atrophy of the corpus callosum and axonal neuropathy
      were demonstrated in 1 sibling who underwent detailed investigation. Review of
      similar cases reported in the literature indicates that this recessively
      inherited disorder probably represents a homogeneous group within the
      heterogeneous cluster of complicated FSP.

PMID- 10893067
TI  - Tapetoretinal degenerations: experiences, experiments and expectations.
AB  - Tapetoretinal degenerations are a common cause for vision problems, but have
      until recently not been amenable to rational treatment. With rapidly increasing
      insights into basic neurobiology and pathobiology this has now begun to change.
      From having been a relatively small group of largely unknown yet fairly prevalent
      disorders, they are rapidly forming a large set of well defined diseases, and it
      is easy to predict that our knowledge about them will continue to increase for
      many years to come. Vitamin A (15,000 IU daily) is currently the only rational
      treatment available. However, in experimental animals, therapy strategies are now
      actively being developed along several different lines. Apoptotic photoreceptor
      cell death can be delayed with different drugs, and at least one of them,
      diltiazem, is approved for human use in cardiovascular diseases. It remains to be
      seen if it has any clinically significant effect in human tapetoretinal
      degenerations. Other strategies aim at counteracting the production of harmful
      protein variants, acting either on DNA or mRNA levels. Transgenes can also be
      used to induce the production of important but missing metabolic components.
      Finally, cells or retina sheets can be transplanted, either to replace failing
      cells or as a source for missing trophic factors. Neither of these strategies has
      yet been transferred to humans, but trials are under way. With the high increase
      in the flow of new information on tapetoretinal disorders, much more precise
      diagnoses and much improved treatments are soon to be expected, augmenting
      considerably the possibilities for ophthalmologists to help patients with such
      diseases. It is not likely that there will be a single treatment for all the many
      varieties. Instead, we are most likely going to see pharmacological treatments
      for some of them, DNA transfers for some, and transplantations for others.

PMID- 10893068
TI  - Cataract surgery and effectiveness. 1. Variation in costs between different
      providers of cataract surgery.
AB  - PURPOSE: To describe and analyse the cost of cataract surgery in four community
      run eye clinics in Sweden and also to analyse differences in cost between these
      clinics. METHODS: The average cost of a cataract surgery episode was calculated
      including one pre-operative visit, the surgery itself and the post-operative
      visits. Included in the analysis were the costs of disposables, personnel, rent,
      depreciation, general anaesthesia, bed days and education. Excluded were the
      costs of complications and overhead costs. RESULTS: The average cost for one
      cataract surgery episode was 5052/6915 SEK (1 Euro = 8.57 SEK) with a variation
      from 4436/6202 to 6130/8293 between the clinics. The lower sum represents a
      minimum cost of personnel, the higher sum a maximum cost. CONCLUSION: A large
      variation in costs of cataract surgery was found in four providers of cataract
      surgery. Nearly all clinics studied had one or more areas with much higher costs
      than average.

PMID- 10893069
TI  - Hyperhomocysteinemia and the MTHFR C677T mutation in central retinal vein
      occlusion.
AB  - BACKGROUND: Hyperhomocysteinemia is a factor that predisposes to thrombosis, and
      the C677T mutation in methylene-tetrahydrofolate reductase (MTHFR) is known to
      give increased plasma homocysteine. We wanted to investigate if these factors
      were overrepresented in a group of patients with central retinal vein occlusion.
      METHODS: 116 patients with a history of central retinal vein occlusion were
      examined for the presence of hyperhomocysteinemia and the MTHFR C677T mutation.
      RESULTS: Compared to the control groups, there was no significant increase,
      neither in plasma homocysteine nor in the frequency of the MTHFR C677T mutation
      in the patients. Even when we looked selectively at the young patients, age less
      than 50 years, no difference could be detected. CONCLUSION: It seems that neither
      hyperhomocysteinemia nor the MTHFR C677T mutation is an important risk factor for
      the aetiology of central retinal vein occlusion.

PMID- 10893070
TI  - Immunolocalization of transforming growth factor-beta1 and tenascin in human
      secondary cataract.
AB  - PURPOSE: This study was carried out to investigate the distribution of
      transforming growth factor-beta1 (TGF-beta1) and the extracellular matrix (ECM)
      glycoprotein tenascin in secondary cataract and anterior subcapsular cataract.
      METHODS: Twenty-four pseudophakic human eyes with secondary cataract, obtained at
      autopsy 1 d to 10 yr (mean 2.4 yr) after cataract surgery, were studied.
      Additionally, a specimen from an anterior subcapsular cataract was included.
      Immunohistochemistry was used to localize TGF-beta1 and tenascin in secondary
      cataract and in anterior subcapsular cataract. RESULTS: Polyclonal antibody to
      TGF-beta1 immunolabelled spindle-shaped cells in the plaques of secondary
      cataract in all eyes. Instead, the cells present in Soemmering's ring cataract
      were not labelled. The ECM in the plaques of secondary cataract was
      immunoreactive for tenascin in all eyes. In anterior subcapsular cataract spindle
      shaped cells and ECM showed similar immunoreactivity. CONCLUSION: Spindle-shaped
      cells that are immunolabelled with TGF-beta1 and ECM showing tenascin-like
      immunoreactivity are present in secondary cataract and in anterior subcapsular
      cataract, thus implicating a possible role in secondary cataract.

PMID- 10893071
TI  - Ocular manifestations of incontinentia pigmenti.
AB  - PURPOSE: The study aimed to evaluate the ocular manifestations in patients with
      incontinentia pigmenti (IP). METHODS: Thirty patients from different parts of
      Sweden participated. Orthoptic and ocular examinations were performed as well as
      evaluation of refraction and visual acuity. RESULTS: Ocular manifestations,
      probably associated with IP, were found in 77% (23/30) of the patients. Thirteen
      had serious or vision-threatening eye manifestations in one eye, of whom 7 were
      totally blind in that eye from retinal detachments. Ten patients had minor
      retinal and/or corneal changes. CONCLUSION: Ocular lesions in patients with IP
      may be serious and lead to blindness because of retinal disease. Ophthalmological
      follow-up is essential in the neonatal period and such a programme is
      recommended.

PMID- 10893072
TI  - Simultaneous, bilateral rhegmatogenous retinal detachment.
AB  - PURPOSE: To examine the incidence, the preoperative findings and the surgical
      outcome of patients presenting with simultaneous, bilateral retinal detachment.
      METHODS: A retrospective analysis of the medical records of patients undergoing
      surgery for rhegmatogenous retinal detachment between 1990 and 1998. RESULTS:
      During this period a total of 827 operations for rhegmatogenous retinal
      detachment were done in 791 consecutive patients. Eighteen patients (2.3%) had
      simultaneous, bilateral retinal detachment, giving an annual incidence of 0.35
      patients per 100,000 population. They all presented with unilateral symptoms.
      Compared with the group of unilateral or consecutive, bilateral retinal
      detachments, patients suffering from simultaneous, bilateral retinal detachments
      were significantly younger, with a mean age of 40.3 years. Thirteen patients had
      multiple, round retinal holes associated with lattice degeneration. Sixteen
      patients were myopic, ranging from -3 to -9.25 diopters. The retina was
      reattached in 35 (97%) of the 36 eyes operated on during the study period.
      CONCLUSION: Simultaneous, bilateral retinal detachment is usually found in
      relatively young, myopic patients with round, atrophic retinal holes, presenting
      with unilateral visual symptoms.

PMID- 10893073
TI  - Retinopathy of prematurity, a decrease in frequency and severity. Trends over 16
      years in a Danish county.
AB  - PURPOSE: To analyse the trends over 16 years (1982-97) in a Danish county
      regarding the clinical appearance of retinopathy of prematurity (ROP). METHODS:
      The data for birth years 1993-97 regarding the regular ophthalmic surveillance
      for ROP in the region have been analysed. With gestational age (GA) 32 weeks
      and/or a birthweight (BW) 1750 g as attempted screening limits a total of 177
      premature infants were surveyed. Comparison was made with studies of a similar
      set-up from the preceding four 3-year periods comprising a total of 814 subjects.
      RESULTS: The number of survivors regarded at a higher risk of developing ROP (GA
      and BW both <32 weeks/1750 g, n=478) showed an even increase over the five
      investigation periods. The ROP frequency, however, fell from a level of 39% to
      10%, there were fewer with severe sequels to ROP, and the children surveyed
      'above limits' eventually avoided ROP. CONCLUSIONS: Using the ROP profile as a
      yardstick for the quality of the neonatal service given to the most immature
      newborns over the period 1982-97, the risk limits regarding GA and BW have gone
      down. More and more of the heavier preterm babies now escape ROP. A significant
      decrease in frequency of ROP in the more immature groups has been observed, and
      fewer cases have progressed to visual impairment.

PMID- 10893074
TI  - Retinopathy of prematurity in a Copenhagen high-risk sample 1997-98. The allover
      surveillance for ROP appears more and more complete.
AB  - PURPOSE: From two recent materials to describe the present clinical status
      regarding retinopathy of prematurity in Denmark, and to outline trends over time.
      METHODS: A) Results of regular ophthalmic surveillance of 201 clinically selected
      (higher risk of ROP than average) pre-term infants of birth year 1997-98 taken
      care of in the two greater Copenhagen tertiary neonatal units, in an intended
      prospective design. Gestational age range was 24-32 weeks at delivery; birth
      weights 490-2200 g. Median values 28 weeks and 1090 g. B) A brief account of the
      latest ROP-associated registrations of visual impairment in Danish children aged
      0-17 years (n=138). RESULTS: A) ROP was observed in 31.3% (n=201). Retinal
      cryotherapy was given to eleven 'own' cases and to two from elsewhere (n=13,
      gestational age at delivery 25-31 weeks). Five had cryotherapy twice. Four of the
      13 were later registered for visual impairment. B) Comparing the first and the
      latest third of the registrations, visual impairment has dropped in frequency and
      severity over the period from 1981 till now. CONCLUSIONS: Compared to previous
      data the present clinical profile of ROP in Denmark indicates a relatively lower
      overall frequency of ROP and a decrease in eventual severe visual impairment.
      Undoubtedly, the continued refinement of neonatal care has been of relevance, but
      the definite decline in visual impairment further reflects a more complete
      ophthalmic surveillance, on a national basis. The advanced cases are generally
      detected in time and retinal ablation therapy offered.

PMID- 10893075
TI  - Bilateral diffuse uveal melanocytic proliferation and uterine cancer. A case
      report.
AB  - PURPOSE: To report a case of bilateral diffuse uveal melanocytic proliferation
      (BDUMP), a rare paraneoplastic syndrome causing visual loss in patients with
      systemic carcinoma. RESULTS: A 70-year-old woman developed visual symptoms 13
      months after surgery and local irradiation therapy for uterine cancer. Following
      bilateral external beam irradiation supplemented with subsequent drainage of
      subretinal fluid in the left eye, the visual acuity improved from 0.01 to 0.15 in
      this eye only. The visual acuity remained at this level until she died 4 1/4
      years after the onset of eye symptoms. CONCLUSION: This is the fourth case that
      survived longer than 24 months after the onset of visual symptoms of the 22
      previously reported cases with BDUMP. It demonstrates that radiotherapy may have
      a vision-preserving effect in this group of patients. The patient also developed
      two different paraneoplastic phenomena--a nephrotic syndrome before and BDUMP
      after treatment for uterine cancer.

PMID- 10893076
TI  - Ganciclovir delivery through an intravitreal microdialysis probe in rabbit.
AB  - The treatment of cytomegalovirus retinitis has during the last years been done
      mainly with sustained release ganciclovir devices implanted in the vitreous. In
      the present study it is shown that ganciclovir can be administered into the
      rabbit vitreous by microdialysis. A concentration of about 10(-6) M, which is
      considered within the therapeutic range, is achieved in the vitreous after a
      microdialysis perfusion. The method offers possibility of variation in the drug
      delivery that is not possible with the ganciclovir implants.

PMID- 10893077
TI  - Sleep disordered breathing: from pathophysiology to evidence-based-medicine.

PMID- 10893078
TI  - Clinical approach to excessive daytime sleepiness.
AB  - Subjective sleepiness is defined as "an elemental feeling state" by which the
      subject, and only him/her knows whether he/she is alert or sleepy. Subjective
      sleepiness has little been used for the clinical evaluation of sleepiness.
      Objective sleepiness is defined as a consequence of the homeostatic need for
      sleep. In the absence of a measurable marker of the fulfillment of the function
      of sleep, the evaluation of objective sleepiness has to rely on a behavioral
      approach based on the postulate that the more you need sleep (i.e., the sleepier
      you are), the more likely you are to fall asleep. However, as for many other
      fundamental human behaviors (drinking, eating, sexual behavior), it is likely
      that the sleeping behavior serves other purposes than its primary objective,
      which distorts the relationship between the observed sleeping behavior and the
      actual need for sleep. The likelihood to fall asleep can be measured by the speed
      with which a sleep episode occurs under standardized laboratory conditions
      (multiple sleep latency test, maintenance of wakefulness test, OSLER test), or by
      the frequency of unwanted sleep episodes under the more naturalistic conditions
      of daily life (Epworth Sleepiness Scale). These various approaches have
      advantages and drawbacks, but none of them can be considered the "gold standard".

PMID- 10893079
TI  - When, where and how to test for sleep apnea.
AB  - This presentation focused on issues relevant to the decision to perform testing
      for sleep disordered breathing. Polysomnographic signals can be captured equally
      well in both the center and in the home, by attended as well as unattended
      monitoring. Attention now is on clinical decisions that best match patient
      presentation to improved clinical outcome. Standardization interpretation can be
      achieved, provided sufficient experience, training, and continued surveillance of
      equipment function. The sleep center must evolve to manage patient with more
      diverse presentations and be a resource for knowledge in sleep and chronobiology
      to a broad range of medical issues and systems.

PMID- 10893080
TI  - Cognitive function in the sleep apnea/hypopnea syndrome (SAHS).
AB  - The magnitude, determinants and reversibility of cognitive deficits associated
      with the sleep apnea/hypopnea syndrome (SAHS) are of clinical and research
      interest. A quantitative overview of impairment effect sizes (ESs) from case
      control studies of cognitive performance in SAHS suggests that deficits broadly
      worsen with disease severity, with large average values for attentional (ES
      approximately 1.0 SD units) and executive (ES approximately 0.9 SD units)
      cognitive scores, and moderate values for memory-related (ES approximately 0.6 SD
      units) performance scores. A study of determinants of cognitive outcomes
      conducted in 150 patients with SAHS (AHI 5+ and > or =2 symptoms) showed
      significant but weak associations between a cognitive 'intellectual ability'
      component score (CS) and both AHI (r=-0.14) and minimum oxygen saturation (r =
      0.15), linking increasing disease severity with poorer performance. A somewhat
      stronger correlation between a cognitive 'response slowing' CS and a
      'wakefulness' CS was observed (r=-0.34). That sleepiness as well as hypoxemia
      might contribute to cognitive deficit has also been suggested by experimental
      sleep fragmentation in normals, producing small to moderate impairments (average
      ES approximately 0.3 SD units) in attention-biased scores. The reversibility of
      attentional cognitive deficits has been investigated through a meta-analysis of
      randomized placebo-controlled crossover studies of CPAP treatment, involving 98
      SAHS patients (AHI 5+ and > or =2 symptoms). While cognitive outcomes showed at
      least trends towards better performance on CPAP than on placebo (p< or =0.1), the
      ESs of cognitive enhancements following CPAP were small (average ES approximately
      0.2 SD units). This may be due either to the relatively mild study population,
      suboptimal CPAP use or to an irreversible component in cognitive impairment in
      SAHS.

PMID- 10893081
TI  - Measuring health related quality of life in sleep apnea.

PMID- 10893082
TI  - Vigilance impairment: assessment by driving simulators.

PMID- 10893083
TI  - Sleepiness at the wheel: symptom or behavior?

PMID- 10893084
TI  - Sleep-disordered breathing and cardiovascular disease: epidemiologic evidence for
      a relationship.
AB  - Epidemiology studies of SDB and CVD to date do not provide a conclusive answer to
      the question of the degree to which SDB impacts CVD or mortality due to CVD.
      However, most of the studies seem to be consistent with a positive, but perhaps
      small, association. All the findings discussed or referred to in this review are
      likely to be biased to some degree. Bias can be both towards underestimation
      (e.g., from mismeasurment of SDB, and over-control for intermediate factors) and
      overestimation (e.g., from inadequate control of confounders and improper
      comparison groups), and the net magnitude of competing biases undoubtedly varies
      from study to study. Small associations were found in the prospective population
      based studies, with one exception. The most obvious methodologic problem in these
      studies would be likely to result in underestimation of the associations. The
      case-control studies, in contrast, showed large associations, but serious biases
      in these studies would probably cause overestimation. Small associations of
      marginal statistical significance were reported from cross-sectional analyses;
      findings were limited by sample size. Although each individual study to date
      could be (and has been ) "dismissed" due to weaknesses, collectively they provide
      evidence that we cannot dismiss the hypothesis that SDB causes CVD. In many
      cases, the weak associations can be explained by problems that likely cause
      underestimation. In fact, finding any association with the limitations of most of
      the past studies is remarkable. Perhaps most important, the findings to date, in
      conjunction with biologically plausible mechanisms have sparked the interest
      needed to initiate the large undertaking of a population-based prospective study.
      The Sleep Heart Health Study (SHHS)15 is a large multicenter prospective study
      specifically designed to investigate the role of SDB in incident coronary heart
      disease, stroke, increased blood pressure, and allcause-mortality. A key feature
      of the study is that home polysomnography studies are performed on a sample of
      6600 men and women, 40 years of age and older, drawn from the samples of other
      longitudinal studies. The new data collected by SHHS can then be linked to the
      large amount of data on cardiovascular risk factors available from the "parent"
      studies. All baseline polysomnography studies have now been completed. Cross
      sectional analyses of SDB and CVD history are now being analyzed, and collection
      of outcome data for longitudinal analyses is underway. Results from SHHS and
      other studies in the near future should greatly increase our ability to assess
      the association of SDB and CVD.

PMID- 10893085
TI  - Cardiovascular consequences of obstructive sleep apnea: experimental hypoxia and
      sympathetic activity.

PMID- 10893086
TI  - Regulation of systemic vasculature in obstructive sleep apnea syndrome.

PMID- 10893087
TI  - Development of the control of breathing: implications for sleep-related breathing
      disorders in infants.
AB  - Abnormal development of the control of breathing has implications for the
      occurrence and severity of SDB during infancy. Prevention of prenatal insults
      such as nicotine exposure should be included in public health programs. Infants
      at risk for SDB or with symptoms of SDB should be investigated for peripheral and
      central chemoreceptor dysfunction. Peripheral chemoreceptor function can be
      assessed using either the hyperoxic test or the alternating breath test, and
      central chemoreceptor function using the rebreathing test. Optimal treatment of
      SDB in the developing infant is of central importance for preserving normal
      behavior and neurocognitive development. Oxygen supplementation and/or
      ventilatory support during sleep prevent uncontrolled episodes of hypoxemia,
      sleep fragmentation, and REM sleep reduction. Finally, alterations in homeostatic
      responses during development may have long-term effects on breathing during sleep
      in childhood and adulthood. In genetically-predisposed subjects, environmental
      conditions during the period of development of respiratory control mechanisms may
      add to the intrinsic vulnerability to SDB.

PMID- 10893088
TI  - Obstructive sleep apnea syndrome: differences between children and adults.
AB  - The obstructive sleep apnea syndrome is a common cause of morbidity in childhood.
      The clinical presentation, pathophysiology, polysomnographic characteristics and
      treatment differ between children and adults. Measurements of the upper airway
      pressure-flow characteristics can be useful in evaluating upper airway function
      in patients with OSAS as well as the normal population.

PMID- 10893089
TI  - Treatment of obstructive sleep apnea syndrome in children.
AB  - Obstructive sleep apnea (OSA) has been identified and recorded in paediatric
      patients, the potential mechanisms for OSA include anatomical abnormalities that
      lead to a narrowed airway space, reduced muscle tone and abnormal central
      ventilatory control. Several treatments have been developed and are routinely
      used to treat OSA in infants and children. Nasal mask continuous positive airway
      pressure (CPAP) is an effective non-invasive treatment that prevents the majority
      of obstructive events, reverses sleep disturbances, improves daytime performance
      and is associated with increased growth in patients with failure to thrive.
      Surgery to correct underlying anatomical abnormalities is frequently used and
      usually results in an improvement in symptoms and in some cases, it is curative.
      Other forms of treatment include pharmacological interventions, positioning and
      nasopharyngeal intubation.

PMID- 10893090
TI  - Effects of CPAP on vigilance and related functions in patients with the sleep
      apnea/hypopnea syndrome.
AB  - There have been relatively few robust studies of the effects of CPAP therapy on
      vigilance and daytime function. This article will use all known published and
      unpublished randomized clinical trials on this area. There is good evidence that
      CPAP helps subjective sleepiness, objective sleepiness, quality of life, mood and
      driving performance. However, CPAP does not appear to normalize objective
      sleepiness. Many of the improvements are directly related to the nightly use of
      CPAP. Recent data suggest that increasing CPAP usage improves outcomes.

PMID- 10893091
TI  - Is more NCPAP better?
AB  - STUDY OBJECTIVES: To assess the benefit of NCPAP in OSA and its relation to the
      degree of use of NCPAP. DESIGN: Randomised parallel controlled one month study
      comparing NCPAP set at therapeutic levels of pressure, with NCPAP set at sub
      therapeutic pressure levels. SETTING: Teaching hospital sleep clinic and
      laboratory SUBJECTS: 101 men referred for investigation of possible OSA who were
      sleepy (Epworth Sleepiness Score > or = 10) and had > or = 10/hr of >4% dips in
      SaO2 due to OSA. OUTCOME MEASURES: Baseline and one month measures of Epworth
      Sleepiness Score (ESS), Maintenance of Wakefulness Test (MWT), and the
      Energy/Vitality dimension of the SF-36 (health status questionnaire). Correlation
      of these outcome measures with NCPAP usage. RESULTS: All outcome measures
      improved significantly more in the therapeutic, compared to the sub-therapeutic,
      group (e.g. ESS 15.0 to 13.0 on sub-therapeutic, and 15.5 to 7.0 on therapeutic,
      p<1x10(-6)). The degree of improvement correlated significantly with NCPAP usage
      in the therapeutic group (ESS, r=-0.60; MWT, r=0.55) but insignificantly in the
      sub-therapeutic group (ESS, r=-0.15; MWT, r=-0.06). Sub-therapeutic NCPAP did not
      improve OSA severity and acted as a control. CONCLUSIONS: NCPAP is clearly
      effective in relieving the sleepiness of OSA compared to a control group
      identical in every way, except for receiving a nasal pressure inadequate to
      control the OSA.

PMID- 10893092
TI  - Cardiovascular effects of continuous positive airway pressure in obstructive
      sleep apnea.
AB  - The cardiovascular sequelae best shown to be associated with OSA are systemic
      hypertension and acute vascular events. The cardiovascular sequelae, including
      acute myocardial infarction or nocturnal angina may be contributed to by arterial
      vasospasm or clot formation in the area of an atheroma. Thus far there are no
      data showing that treatment of OSA eliminates vascular sequelae, but much
      evidence shows that chronic CPAP therapy may lower elevated blood pressure in
      some patients. However, for a variety of reasons mentioned above, CPAP does not
      correct hypertension in all OSA patients.

PMID- 10893093
TI  - Compliance, education, monitoring in the treatment of obstructive sleep apnea by
      nasal continuous positive airway pressure.

PMID- 10893094
TI  - Is treatment of obstructive sleep apnea syndrome with auto-CPAP useful?
AB  - Automatic CPAP therapy has been developed to constantly adapt the positive
      pressure level to the required needs. The automatic devices have been used in two
      different ways, one being to determine the pressure level to be prescribed at
      home for fixed CPAP therapy, and the other one to replace fixed CPAP as an home
      treatment. This last application should alleviate the need for a titration study.
      The benefits reported up to now in the literature vary from one machine to
      another, but usually these machine are effective in abolishing obstructive
      breathing disturbances and the consecutive sleep fragmentation. The mean positive
      pressure level applied during automatic CPAP treatment is usually less than the
      effective pressure level measured during a conventional titration sleep study.
      Some results suggest that automatic CPAP therapy may improve compliance to CPAP
      therapy. There is a need to better define if automatic CPAP therapy may benefit
      to specific groups of sleep apnea patients.

PMID- 10893095
TI  - Principles of mandibular advancement device applied to the therapeutic of snoring
      and sleep apnea syndrome.
AB  - Mandibular advancement device (MAD) represents a therapeutic option for simple
      snoring to obstructive sleep apnea syndrome (OSAS). The different available
      studies report an improvement either on nocturnal respiratory events or on the
      quality of sleep. The decrease in the intensity of snoring is confirmed by the
      patient's partner and by objective studies. For the time being the effects of
      these mandibular advancement devices on the upper airway resistance syndrome has
      not yet been well documented. The significant clinical improvement is secondary
      to the decrease in apnea hypopnea index (AHI). A polysomnographically proved cure
      has been reported with AHI < 10/h. Sleep architecture is also improved with
      wearing MAD demonstrating a decrease in the time passed in stage 1 sleep and an
      increase in slow wave sleep and rapid eye movement sleep (REM). A decrease in
      microarousals index has been shown. Daytime vigilance disorders are subjectively
      and objectively less remarkable. Then MAD can be beneficial for mild to moderate
      SAOS.

PMID- 10893096
TI  - Treatment, airway and compliance effects of a titratable oral appliance.
AB  - STUDY OBJECTIVES: To measure the effects of a titratable anterior mandibular
      repositioner on airway size and Obstructive Sleep Apnea (OSA) and to evaluate its
      compliance. DESIGN: Before and after insertion sleep studies were obtained in a
      total of 38 OSA patients of varying severity from three different sites. Covert
      compliance was measured by means of a newly-developed, miniaturized, temperature
      sensitive, imbedded monitor. Validity testing was completed in six adult
      volunteers who wore monitors imbedded into small acrylic appliances. MEASUREMENTS
      AND RESULTS: The mean RDI before treatment was 32.6 (SEM 2.1) and after the
      insertion of the appliance, the RDI was reduced to 12.1 (SEM 1.7, p<0.001). RDI
      was reduced to less than 15/hour in 80% of a group of moderate OSA patients (RDI
      15 to 30) and in 61% of a group of severe OSA patients (RDI > 30) with respect to
      baseline RDI. Fiber optic video endoscopy was performed on 9 OSA patients with
      and without the appliance. No significant differences in hypopharynx or
      oropharynx cross sectional areas were found, but at the level of the velopharynx,
      the airway size was significantly increased (p<0.05). The index of agreement was
      0.99 between the monitor clock time and the subject's log sheets. Compliance data
      from eight OSA subjects instructed to wear the appliance during sleep indicated
      that it was worn for a mean of 6.8 hours with a range of 5.6 to 7.5 hours per
      night. CONCLUSION: The titratable adjustable mandibular advancement appliance,
      made from thermoelastic acrylic, significantly reduces RDI in moderate to severe
      OSA patients, has a direct effect on airway size and is well worn throughout the
      night.

PMID- 10893097
TI  - Is there a rationale in modulating brainstem neurons in obstructive sleep apnea
      and is it clinically relevant?

PMID- 10893098
TI  - Radiofrequency (pacing and thermic effects) in the treatment of sleep-disordered
      breathing.
AB  - Radiofrequency, whether it is used for pacing or for its thermal liberation
      properties, has been investigated as a treatment for sleep-disordered breathing.
      Diaphragmatic pacing has a long history. The problems associated with pacing,
      which are related to patient selection, equipment failure, disturbances at the
      electrode/nerve interface, neuromuscular function failure, muscle fatigue, and
      the physiological consequences of stimulation, will have to be resolved with
      XIIth nerve stimulation. Radiofrequency thermal ablation has been applied on the
      tongue of an animal model. In man, turbinates, soft palate tissue and the base of
      tongue have been treated. These feasibility studies have demonstrated that
      obstructive sleep apnea syndrome and upper airway resistance syndrome can be
      completely controlled using radiofrequency thermal ablation in some subjects.
      These results can be obtained without complications related to speech, taste or
      swallowing. The treatment can be administered as an outpatient procedure, but
      many applications are needed, and treatment may span 6 months. Too high a level
      of radiofrequency will cause pain or otherwise avoidable complications. The
      determination of which patients will benefit most from these procedures will
      require further multi-center, placebo-controlled studies.

PMID- 10893099
TI  - Obstructive sleep apnea syndrome: who should be treated?
AB  - Most, if not all patients referred for assessment require some form of
      therapeutic intervention. In particular, general lifestyle advice, sleep hygiene,
      and weight reduction in overweight patients should always be promoted, even where
      additional specific therapy such as NCPAP is also being considered. Treatment
      decisions are relatively easy at the extremes of the clinical spectrum, but there
      is an increasing choice of therapeutic options available for those patients in
      the mid-range of severity. Criteria based on AHI levels are inappropriate to
      dictate treatment choice, particularly NCPAP.

PMID- 10893100
TI  - Should primary snoring be treated?

PMID- 10893101
TI  - Definition and diagnosis of upper airway resistance syndrome.

PMID- 10893103
TI  - Nocturnal hypoventilation in chronic respiratory failure.

PMID- 10893102
TI  - Upper airway resistance syndrome and its treatment.
AB  - Although upper airway resistance syndrome (UARS) is being recognized by a growing
      number of specialists, its prevalence remains unknown. UARS is associated with
      nocturnal and daytime complaints and oro-naso-maxillo-mandibular signs. Spectrum
      analysis of the nocturnal sleep EEG from the central leads indicates significant
      differences in absolute power in the 12-14 Hz and the 7-9 Hz bands of UARS
      patients compared to controls. The 0.5-2.0 Hz band also appears to be involved
      when analyses performed on matched controls are compared to results obtained in
      subjects treated with nasal CPAP. Several treatment avenues--nasal CPAP, dental
      devices, surgical procedures, and radiofrequency thermal ablation--have been used
      for the treatment of UARS. The number of subjects treated have been too low and
      the protocols too limited to arrive at appropriate outcome recommendations, but
      many of the approaches have shown positive results, suggesting the possibility of
      several treatment avenues.

PMID- 10893104
TI  - Nocturnal hypoventilation in chronic respiratory failure (CRF) due to
      neuromuscular disease.
AB  - Decrease of respiratory muscle capacities in neuromuscular disease can lead to
      chronic respiratory failure with permanent alveolar hypoventilation. Respiratory
      centers elaborate a strategy of breathing dedicated to prevent overt respiratory
      muscles fatigue. This strategy may worsen chronic hypercapnia. During sleep,
      ventilation decreases because a lessening in respiratory centers function. During
      NREM sleep hypoventilation is only an exacerbation of what is seen during
      wakefulness. During REM sleep, atonia worsens much more hypoventilation
      particularly when diaphragmatic function is impaired. The effects of atonia are
      amplified by a very low reactivity of respiratory centers. Nocturnal mechanical
      ventilation improves nocturnal hypoventilation and daytime arterial blood gases
      (ABG). Mechanism of improvement in ABG and how nocturnal hypoventilation and
      diurnal hypoventilation interact, are still a matter of debate.

PMID- 10893105
TI  - Non-invasive ventilation during sleep.

PMID- 10893106
TI  - Pathophysiology of central sleep apnea syndrome.

PMID- 10893107
TI  - Central sleep apnea and chronic heart failure.
AB  - Central sleep apnea with Cheyne-Stokes respiration (CSR) during sleep affects
      about 40 % of patients with chronic heart failure (CHF). During CSR simultaneous
      periodic fluctuations in wakefulness and respiration with accompanying changes in
      blood pressure and heart rate are observed. CSR can be described as an
      oscillation of the ventilatory feedback loop controlling respiration. The major
      synergistically acting mechanisms causing this oscillation include reduced body
      stores of oxygen and carbon dioxide, hyperventilation with concomitant
      hypocapnia, prolonged circulation time, and a relatively high hypercapnic
      ventilatory response. The repetitive desaturations and arousals following CSR
      cause daytime symptoms and an increase in sympathetic activity. In CHF
      chronically increased sympathetic activity has negative effects on left
      ventricular function and is associated with reduced exercise tolerance and poor
      prognosis. Therefore CSR is expected to have an unfavorable influence on the
      course of CHF. Whether successful treatment of nocturnal CSR has any impact on
      the high mortality of CHF needs to be resolved in controlled studies with
      sufficient sample size.

PMID- 10893108
TI  - Treatment of central sleep apnea in heart failure.
AB  - Recent studies show that central sleep apnea occur in about 40% of patients with
      heart failure and systolic dysfunction. The pathophysiological consequences of
      central sleep apnea may contribute to morbidity and mortality of heart failure.
      Three treatment modalities, oxygen, continuous positive airway pressure and
      theophylline have been shown to decrease periodic breathing modestly with
      considerable improvement in arterial oxyhemoglobin desaturation, and variable
      effects on sleep characteristics. However, long-term effects of central sleep
      apnea and its treatment on the natural history of heart failure remain to be
      determined.

PMID- 10893109
TI  - Further discussion of SP checklists and videotaped performances.

PMID- 10893110
TI  - Further discussion of SP checklists and videotaped performances.

PMID- 10893111
TI  - CurrMIT: you've gotta use this thing!

PMID- 10893112
TI  - The National Quality Forum seeks to improve health care.

PMID- 10893113
TI  - Managed care for uninsured patients at an academic health center: a case study.
AB  - In 1997, the University of New Mexico Health Sciences Center ("the Center")
      created a managed care plan ("the Plan") for its uninsured patients who were
      county residents. The Plan's features include pooling the resources of existing
      county safety-net providers, enrolling patients with primary care providers at
      easily accessible neighborhood-based clinics, and investing in social support
      services, case management, and 24-hour telephone triage. After two years of the
      Plan's operation, the utilization of ambulatory care services by Plan enrollees,
      the number of discharges per 1,000 enrollees from the Center-affiliated
      University Hospital, and the number of hospital days per 1,000 enrollees had all
      dropped significantly (p < .001 for all). For the 13,114 enrollees in the Plan,
      University Hospital saved an estimated $1,904,872 per year in costs. The
      replacement of unpaid hospital days with paying patients is estimated to have
      yielded over $695,000 in additional revenues per year. The authors conclude that
      managing the care of uninsured patients in an academic health center can reduce
      ambulatory care and inpatient utilization and reduce the cost of care. To achieve
      these favorable outcomes requires the organization of services to meet the unique
      needs of the uninsured and underserved population.

PMID- 10893114
TI  - Using faculty development to solve a problem of evaluation and management coding:
      a case study.
AB  - Compliance with billing and coding rules put forth by the Health Care Finance
      Administration (HCFA) is a challenge for practicing physicians, including those
      in academic settings. The authors, members of the academic practice at Wayne
      State University School of Medicine, Department of Family Medicine, designed and
      delivered a comprehensive curriculum as part of the practice's faculty
      development initiative surrounding the coding challenge. The authors defined
      outcomes expected on the way to achieving 100% compliance with HCFA's guidelines.
      Their curriculum covered topics of coding theory, chart auditing for coding, team
      building, effective meetings, and structured problem solving. The curriculum was
      delivered from January to May 1998. Chart audits of 251 charts (office notes)
      from before the intervention and 263 charts from after the intervention were
      performed to evaluate differences in coding accuracy. Errors were significantly
      reduced. The total error rate dropped from 50.2% to 31.1% (p < .05). Overcoding
      errors were reduced by one third (29.1% versus 19.7%), while undercoding errors
      were reduced by half (16.3% versus 8.4%). Other errors fell from 4.7% to 3%. The
      approach of defining and developing work teams and then using standard quality
      improvement tools may be an effective way to improve compliance with HCFA billing
      and coding rules. In addition, faculty development can be incorporated into the
      process of solving a problem that faces a faculty.

PMID- 10893115
TI  - Should U.S. academic health centers play a leadership role in global health
      initiatives? Observations from three years in China.
AB  - Based on his work in Shanghai, China, the author believes that U.S. academic
      health centers (AHCs) should take a leadership role in global health initiatives.
      While acknowledging that most AHCs already have focused projects involving
      research or education with foreign institutions, he proposes a greater
      coordination of these projects into programs that, in some areas, could also be
      linked to clinical delivery systems where care may be provided. These AHC
      "platforms" overseas would be structured as a partnership between an AHC in the
      United States and one in the foreign country where the platform is located, to
      promote their missions of education, research, and service. For example, U.S.
      AHCs benefit, and are often dependent upon, international trainees who seek
      further clinical or research training in the United States. However, the
      identification of suitable candidates and career guidance, so the students'
      career choices could benefit their home countries, are often lacking. Thus, the
      United States is often viewed as facilitating a "brain drain" of future leaders
      in academic medicine from developing areas of the world. The author proposes a
      way to lessen this problem by shifting more on-site training to settings in the
      students' home countries, which could occur if AHCs were willing to develop
      overseas platforms. U.S. students would also benefit from access to medical
      training in foreign lands for both the cultural perspectives they offer and the
      unique diseases and medical situations encountered. He also suggests that shared
      platforms would lead to greater research opportunities for institutions in the
      United States and abroad. He argues for increased efforts at coordinating these
      activities with the rising demand for Western clinical services by multinational
      companies and U.S. expatriate communities overseas. The potential pitfalls of
      such initiatives as well as the need for permanent relationships are discussed.
      In conclusion, he believes that AHCs have an opportunity to establish global
      health initiatives through education, research, and patient care that will both
      enhance their own institutions and benefit the international community.

PMID- 10893116
TI  - Teaching medical students social responsibility: the right thing to do.
AB  - As academic medicine has become more focused on the economic pressures of the
      marketplace, some educators have expressed concern about whether appropriate
      attention is being given to the character development and moral education of
      medical students. The authors conclude that medical schools do indeed have a duty
      to teach their medical students to be socially responsible. They define a
      socially responsible individual as a person who takes part in activities that
      contribute to the happiness, health, and prosperity of a community and its
      members. They suggest that medical students should participate in carefully
      designed, socially responsible activities in order to (1) practice and have
      reinforced such qualities as reliability, trustworthiness, dependability,
      altruism, and compassion; (2) partially reimburse society for the cost of their
      medical education; (3) increase their exposure to a population-based approach to
      health care; and (4) help medical schools fulfill their social contract with the
      public. The authors outline the process for developing a curriculum to teach
      social responsibility to medical students and list some of the key questions
      faculty and administrators must address in the processes of development and
      implementation. They conclude that while faculty responsible for implementing a
      curriculum in social responsibility must be highly committed and prepared to
      address numerous difficult questions concerning the curriculum's philosophy,
      structure, and function, the potential benefits of such a curriculum are well
      worth the effort.

PMID- 10893118
TI  - Medicine and the arts. John Doe No. 24.

PMID- 10893117
TI  - The historical method of teaching clinical medicine. 1927.

PMID- 10893119
TI  - A pre-admission program for underrepresented minority and disadvantaged students:
      application, acceptance, graduation rates and timeliness of graduating from
      medical school.
AB  - PURPOSE: To determine whether students' performances in a pre-admission program
      predicted whether participants would (1) apply to medical school, (2) get
      accepted, and (3) graduate. METHOD: Using prospectively collected data from
      participants in the University of North Carolina at Chapel Hill's Medical
      Education Development Program (MEDP) and data from the Association of American
      Colleges Student and Applicant Information Management System, the author
      identified 371 underrepresented minority (URM) students who were full-time
      participants and completed the program between 1984 and 1989, prior to their
      acceptance into medical school. Logistic regression analysis was used to
      determine whether MEDP performance significantly predicted (after statistically
      controlling for traditional predictors of these outcomes) the proportions of URM
      participants who applied to medical school and were accepted, the timeliness of
      graduating, and the proportion graduating. Odds ratios with 95% confidence
      intervals were calculated to determine the associations between the independent
      and outcome variables. RESULTS: In separate logistic regression models, MEDP
      performance predicted the study's outcomes after statistically controlling for
      traditional predictors with 95% confidence intervals. CONCLUSIONS: Pre-admission
      programs with similar outcomes can improve the diversity of the physician
      workforce and the access to health care for underrepresented minority and
      economically disadvantaged populations.

PMID- 10893120
TI  - Medical and veterinary students' structural knowledge of pulmonary physiology
      concepts.
AB  - PURPOSE: The goal of this study was to assess quantitatively medical and
      veterinary students' knowledge structures of 12 pulmonary physiology concepts
      before and after receiving a focused instructional block. The "goodness of fit"
      and internal consistency reliability of the students' knowledge structures were
      evaluated. Indexes of the students' structural knowledge were correlated with
      customary measures of student learning of the same concepts. METHOD: Knowledge
      structures were assessed using a questionnaire that requested similarity
      judgments about all possible pairs of the concepts: n(n - 1)/2 = 66 pairs. The
      similarity judgment data were analyzed using the individual differences (INDSCAL)
      model of multidimensional scaling (MDS). Dimension weights for individual
      students were then correlated with their final examination scores. RESULTS: A
      four-dimensional MDS solution provided the best structural fit to the pairwise
      concept-similarity data. Dimension 1 ranges from control of breathing to lung gas
      exchange. Dimension 2 ranges from control of breathing to respiratory mechanics.
      Dimension 3 separates perfusion from diffusion. Dimension 4 addresses ventilatory
      control. Hierarchical concept clusters are located within this framework.
      However, indexes of structural learning did not correlate with other measures of
      knowledge about the same concepts. CONCLUSION: The study outcomes, in contrast to
      research in other fields, suggest that structural knowledge in this domain
      differs from knowledge assessed by standard examinations. Further research
      involving other basic science or clinical concept sets is needed to verify or
      refute this finding.

PMID- 10893121
TI  - Sequential testing in the assessment of clinical skills.
AB  - PURPOSE: Educators who use standardized-patient-based (SP-based) tests may save
      resources by using sequential testing. In this approach, students take a short
      screening test; only those who fail take a second test. This study investigated
      whether sequential testing increases efficiency with only a minor decrease of
      validity. METHOD: In 1994-95, first- through fourth-year (Group 1) and sixth-year
      (Group 2) medical students at the University of Maastricht took SP-based tests.
      Each test took two days. In a simulation experiment based on the data from those
      tests, the authors considered the first day as the screening test and the second
      day as the second test. They investigated efficiency and validity as a function
      of the cutoff score of the screening test. They developed and evaluated a new
      method to determine the optimum cutoff score of the screening test, a method
      based on minimization of the loss represented by the (weighted) numbers of false
      positives and negatives in the screening test. RESULTS: The negative predictive
      value (probability that a student would fail the complete test if he or she had
      failed the screening test) was low (<60%), while the positive predictive value
      was high (>96%). Accordingly, stringent pass/fail cutoff scores in the screening
      test (75% for Group 1 and 80% for Group 2) produced optimum results. Using those
      cutoff values, only 26% and 11% of 'the students would have had to take the
      complete test to get a "true" score, while only 0.2% and 0.0% of the students who
      passed the screening test went on to fail the complete test (false positives).
      CONCLUSIONS: In a sequential SP-based test, the pass/fail cutoff score of the
      screening test should be stringent. This can considerably reduce testing time
      (30% to 40%), while keeping the percentage of false positives at an acceptably
      low level of less than 0.2%. As an alternative to receiver operator
      characteristic analysis, minimization of the loss function was found to be an
      appropriate method to determine the optimum cutoff value of the screening test.

PMID- 10893122
TI  - Medical students' self-assessments and their allocations of learning time.
AB  - PURPOSE: To investigate the impact of self-assessed diagnostic strengths and
      weaknesses on medical students' allocation of learning time (one indicator of
      self-directed learning) during a third-year internal medicine clerkship. METHOD:
      In 1997-98, 107 students at the University of Michigan Medical School self
      assessed their diagnostic skills in 14 clinical areas before and after the
      clerkship and reported the relative amounts of time spent learning about these
      topics during the clerkship. RESULTS: Individual-level analyses indicated that,
      for the average student, self-assessed strengths and weaknesses did not correlate
      with allocation of educational time, but that time allocation was positively
      related to changes in self-assessed skill. Considerable variations in these
      relationships, however, suggest a need for closer study. CONCLUSION: Although
      individual students evidenced different levels of self-directed learning, this
      study suggests overall that students at this level of training are neophytes in
      applying both information generated through self-assessment and principles of
      self-directed learning in their clinical education. Attempts to advance students
      beyond this level depend on many factors, including the extent to which the
      learning environment encourages or even permits self-directed learning, the
      progression and time frame through which students become self-directed
      practitioners, and the impact of educational interventions to promote this
      development.

PMID- 10893123
TI  - When should learning about hospitalized patients end? Providing housestaff with
      post-discharge follow-up information.
AB  - PURPOSE: As hospital stays grow shorter, many patients are discharged to follow
      up with their primary care physicians before their diagnoses and responses to
      treatment are clear. The authors studied the value and feasibility of providing
      housestaff with follow-up information about their former inpatients. METHOD:
      Patients included in the study (1) had been admitted to the housestaff service
      during the study period (January to March 1997), (2) had received follow-up care
      from a primary care physician in the Johns Hopkins Bayview Physicians'
      Professional Association, and (3) had been hospitalized for at least three days.
      The primary care physician completed a single-page follow-up form four to six
      weeks after the patient's discharge from the hospital; that form was given to the
      house officers who had cared for that patient. RESULTS: Responses to a
      preintervention questionnaire completed by 28 of 39 house officers (72%) showed
      that 92% felt it to be important or extremely important to get follow-up
      information about inpatients; 86% indicated that they rarely or never receive
      such information. During the study period, house officers were sent follow-up
      information for 65 of 76 eligible patients (85%). In their responses to a post
      intervention questionnaire (response rate 73%), the house officers most valued
      learning about the accuracy of the discharge diagnosis, the results of additional
      diagnostic tests, and information about the patient's quality of life since
      discharge. Housestaff's satisfaction with the follow-up information received
      about inpatients improved (p = .001). CONCLUSIONS: Providing follow-up
      information was a feasible intervention that was valued by housestaff.

PMID- 10893124
TI  - Are medical students comfortable with practicing physical examinations on each
      other?
AB  - PURPOSE: To assess medical student attitudes toward, and comfort with, taking
      turns practicing peer physical examinations (PPEs) on fellow classmates. METHOD:
      A questionnaire with 25 Likert-scaled questions was administered to 164 end-first
      year medical students at the University of Minnesota, Minneapolis. Topics
      assessed included: (1) comfort with various aspects of PPEs; (2) attitudes
      regarding the professionalism, appropriateness, and perceived value of PPEs; (3)
      attitudes toward peer breast, genital, and rectal exams; and (4) the effects of
      age and gender on response. RESULTS: Of the 164 students surveyed, 124 (76%)
      responded. Almost all (98%) agreed that PPEs are appropriate, valuable, and a
      comfortable experience. Fewer students were comfortable with performing inguinal
      examinations and conducting PPEs with students of the opposite gender. Twelve
      percent of the students expressed difficulty in setting limits with peers, and
      48% felt exposed when undressed as an examination model in front of a group of
      peers. The majority of students were opposed to peer breast, genital, and rectal
      examinations. Some statistically significant gender differences and age/gender
      interactions were observed. CONCLUSION: Results suggest that this sample of
      medical students was very comfortable with PPEs and willing to participate in
      PPEs, although a few students were uncomfortable with these examinations. No
      extensive curricular change appears warranted, though steps can be taken to
      maximize overall student comfort and to accommodate the few students who do not
      favor PPEs.

PMID- 10893125
TI  - Introduction to human health and illness: a series of patient-centered
      conferences based on the biopsychosocial model.
AB  - In 1985, to increase the curricular presence of the biopsychosocial model of
      medical education, the University of Rochester School of Medicine and Dentistry
      introduced a series of whole-class, patient-centered conferences for all first-
      and second-year medical students. From 1985 through the spring of 1999, these
      sessions, called Introduction to Human Health and Illness (IHHI), were offered as
      a stand-alone course every Friday in the first two years of medical school;
      beginning in the fall of 1999, the sessions were integrated into other first- and
      second-year courses. With real patients present, these conferences focus on the
      relationships among biological, behavioral/psychological, and social factors in
      health and illness. Some of the sessions also explore the impact of physician
      behaviors on patients and their health and the roles of other professionals in
      patient care. The authors describe the creation and implementation of the IHHI
      course, organization, format, and faculty for the IHHI sessions, the
      opportunities the sessions provide for active student learning and interaction
      with patients, and their multidisciplinary content. Descriptions of specific
      sessions and a summary of the program's strengths, limitations, and opportunities
      for the future are also presented.

PMID- 10893126
TI  - Horses and the diphtheria antitoxin.

PMID- 10893127
TI  - Project Medishare: a volunteer program in international health at the University
      of Miami.
AB  - Most U.S. medical schools have programs in international health, but there is a
      need to find ways to make students (particularly those with little clinical
      experience) more effective volunteers in international settings. The Department
      of Family Medicine at the University of Miami School of Medicine developed a
      program to help prepare students for international work and to ensure that the
      work they do makes a difference. Over the past four years, this program, Project
      Medishare, has sent groups of students to Haiti to conduct health fairs. Students
      prepare all year for their voluntary trips, which take place during the spring
      and summer breaks; they learn about Haiti's history, culture, language, and
      health problems. They also raise funds and donations of medicine and supplies.
      The health fairs, which are one-day events in orphanages and villages, emphasize
      patient education and preventive medicine. The success of the fairs is evaluated
      using testimonials from Haitian officials and patients, students' journals, and
      data collected by the students. Factors critical to Project Medishare's success
      include (1) having a "critical mass" of culturally and linguistically competent
      students and faculty; (2) collaboration with local authorities and providers; (3)
      advance preparation; and (4) using lessons learned from each event to improve the
      next.

PMID- 10893128
TI  - A special course for premeds and biology majors at Hofstra University.
AB  - Three years ago the biology department at Hofstra University began to offer an
      innovative course for premeds and biology majors. "Applications of Basic Science
      to Cardiovascular Medicine," taught by a practicing cardiologist, demonstrates
      why students must master basic science in order to understand the mechanisms and
      treatment of disease.

PMID- 10893129
TI  - Endotension after endovascular aneurysm repair: definition, classification, and
      strategies for surveillance and intervention.
AB  - In the ongoing evolution of a categorization system for endoleak, the authors
      propose the term endotension to define persistent or recurrent pressurization of
      the aortic aneurysm sac after endovascular repair. Endotension is evidence that
      the aneurysm remains at risk of rupture and should, therefore, be considered an
      indication for secondary intervention. Management strategies and a grading system
      for endotension are offered.

PMID- 10893130
TI  - Endotension: an explanation for continued AAA growth after successful endoluminal
      repair.
AB  - PURPOSE: To present and analyze several cases that illustrate persistent sac
      pressurization following endovascular abdominal aortic aneurysm (AAA) repair.
      METHODS AND RESULTS: Four patients with successful endovascular AAA exclusion
      presented in follow-up with an expanding aneurysm. Two had initial sac diameter
      decrease, but by 18 and 24 months, respectively, the AAA had enlarged and become
      pulsatile. There was no endoleak evident, but the proximal attachment stents had
      mig rated distally in both cases. One patient developed endoleak with aneurysm
      expansion at 6 months; contained rupture occurred at 12 months. The last case had
      slowly evolving aneurysm expansion over 36 months but no endoleak. All endografts
      were removed and successfully replaced with conventional grafts. Intrasac
      thrombus was implicated as the means of pressure transmission that precipitated
      AAA expansion in these cases. CONCLUSIONS: Excluded AAAs can increase in size
      owing to persistent or recurrent pressurization (endotension) of the sac even
      when there is no evidence of endoleak. One proposed mechanism is pressure
      transmission via thrombus that lines the attachment site. Endotension may also
      represent an indiscernible, very low flow endoleak that allows blood to clot at
      the source of leakage.

PMID- 10893131
TI  - Outpatient carotid artery stenting: a case report.
AB  - PURPOSE: To report a case of carotid artery stenting for asymptomatic carotid
      restenosis performed in an outpatient setting. METHODS AND RESULTS: A 68-year-old
      man with right carotid restenosis after repeat carotid endarterectomy underwent
      carotid angioplasty and stenting on an ambulatory basis. The procedure to implant
      a Smart stent required 45 minutes; the femoral access site was closed with a
      puncture closure device. The patient experienced no sequelae to this procedure
      and is well 6 months after treatment. CONCLUSIONS: Outpatient delivery of
      percutaneous carotid stenting may be feasible in appropriately selected patients.

PMID- 10893132
TI  - Outpatient carotid stenting: feasible, yes, but advisable?

PMID- 10893133
TI  - Carotid stenting with cerebral protection: first clinical experience using the
      PercuSurge GuardWire system.
AB  - PURPOSE: To study the feasibility and safety of carotid angioplasty and stenting
      using a new cerebral protection device that temporarily occludes the distal
      internal carotid artery (ICA). METHODS: Forty-eight high-risk patients (39 men,
      mean age 69.1 +/- 8 years, range 54 to 86) with 53 ICA stenoses underwent
      percutaneous angioplasty and stenting via the femoral approach under cerebral
      protection afforded by a 0.014-inch GuardWire balloon occlusion device. Mean
      stenosis was 82.1% +/- 9.65% (range 70 to 96) and mean lesion length was 16.0 +/-
      7.5 mm (range 6 to 50). Thirty-three (62%) lesions were calcified, and 38 (72%)
      were ulcerated. Thirty-two (60%) of the lesions were asymptomatic. With the
      occlusion balloon inflated in the distal ICA, the lesion was dilated and stented.
      The area was cleaned by aspiration and flushed via an aspiration catheter
      advanced over the wire. Blood samples were collected from the external carotid
      artery (ECA) and analyzed to measure the size and number of particles collected.
      Computed tomography and neurological examinations were performed the day after
      the procedure. RESULTS: Immediate technical success was achieved in all patients
      with the implantation of 38 Palmaz stents, 8 Expander stents, and 11 Wallstents.
      Carotid occlusion was well tolerated in all patients but 1 who had multiple,
      severe carotid lesions and poor collateralization. Mean cerebral flow occlusion
      time was 346 +/- 153 seconds during predilation and 303 +/- 143 seconds during
      stent placement. Total mean flow occlusion time was 542 +/- 243 seconds. One
      immediate neurological complication (transient amaurosis) occurred in a patient
      who had an anastomosis between the external carotid (EC) and ICA territories.
      Debris was removed in all patients with a mean 0.8-mm diameter catheter.
      CONCLUSION: Cerebral protection with the GuardWire device is easy, safe, and
      effective in protecting the brain from cerebral embolism. Larger studies are
      warranted.

PMID- 10893134
TI  - Neurological monitoring during carotid artery stenting: the Duck Squeezing Test.
AB  - PURPOSE: To examine the usefulness of a novel method for neurological monitoring
      during carotid artery stenting (CAS). METHODS: The records of patients who
      underwent elective CAS between June 1996 and October 1998 were reviewed to
      identify those who had neurological changes during the procedure. We examined
      whether the neurological change had been detected by a change in the ability of
      the patient to respond to predetermined commands involving a small rubber duck
      placed in the contralateral hand. RESULTS: hundred seventy patients (320 vessels)
      underwent monitoring using the Duck Squeezing Test; 10 suffered neurological
      events during the procedure. Four of these were transient and temporally related
      to balloon inflation. Another 6 were tentatively ascribed to distal embolism. All
      instances were accompanied by a change in the patient's ability to perform the
      Duck Squeezing Test, which allowed the identification of the abnormal clinical
      situation. In addition, there were 4 false-positive tests secondary to the
      patient accidentally dropping the rubber duck. CONCLUSIONS: The Duck Squeezing
      Test is a sensitive and specific method for monitoring patients during elective
      CAS. Its practical applicability is based on sound neurophysiological concepts,
      which underscore the clinical importance of the test.

PMID- 10893135
TI  - Intraventricular hemorrhage after carotid stenting.
AB  - PURPOSE: To report an important complication related to carotid stenting. METHODS
      AND RESULTS: A 71-year-old man with symptomatic subtotal occlusion of the left
      internal carotid artery had a 30-mm lesion treated percutaneously with
      implantation of 2 stents. Although the procedure was completed satisfactorily,
      left intraventricular hemorrhage occurred 4 hours later, possibly related to
      hyperperfusion injury. The patient expired 30 days after the stent procedure.
      Preoperative single-photon emission computed tomography revealed severely reduced
      vasoreactivity in the affected territory after acetazolamide challenge.
      CONCLUSIONS: The risk of hyperperfusion injury must be considered and minimized
      in patients with significant restriction of regional vasoreactivity. We recommend
      that cerebral hemodynamic status be determined prior to carotid stenting.

PMID- 10893136
TI  - Relocation of the iliac artery bifurcation to facilitate endoluminal treatment of
      abdominal aortic aneurysms.
AB  - PURPOSE: To report a surgical technique to preserve the internal iliac arteries
      (IIAs) and facilitate endovascular repair of abdominal aortic aneurysms (AAAs)
      with extensive iliac artery involvement. TECHNIQUE: A new iliac artery
      bifurcation is created surgically through an 8-cm lower left abdominal incision
      by implanting the IIA onto the distal external iliac artery either directly or by
      using a tube graft interposition. Careful technique is required to avoid embolic
      complications, but after relocating the bifurcation, aortic endografting can be
      performed, either simultaneously or staged, depending upon patient
      characteristics. CONCLUSIONS: Relocation of the iliac artery bifurcation appears
      to be a good alternative to preserve pelvic arterial flow in selected candidates
      for endoluminal AAA repair.

PMID- 10893137
TI  - Iliac bifurcation relocation: more complex and controversial.

PMID- 10893138
TI  - Endovascular AAA repair: prevention of side branch endoleaks with thrombogenic
      sponge.
AB  - PURPOSE: To report a technique that might decrease the incidence of lumbar artery
      endoleaks following endovascular repair (EVR) of abdominal aortic aneurysms
      (AAAs). METHODS: Ninety-three patients (86 males, median age 72 years, range 56
      to 88) undergoing EVR with the aortomonoiliac technique were entered into a study
      to detect and then occlude patent side branches before completion of the
      endografting procedure. Prior to deploying the iliac occluder, an aneurysmogram
      was performed to detect patent aortic side branches. If these side branches were
      found, an absorbable gelatin sponge was inserted into the aneurysm sac via the
      occluder introducer sheath. The patients were followed with contrast-enhanced
      spiral computed tomography (CT) at 1 week and 3, 6, and 12 months to detect the
      presence of endoleaks. RESULTS: Forty-eight (52%) patients demonstrated patent
      side branches that were occluded by the insertion of gelatin sponges into the
      aneurysm sac. The remaining 45 patients without evidence of side branch flow were
      untreated. Ten (10.7%) patients died in the perioperative period, and 15 (16.1%)
      primary endoleaks (13 proximal, 2 distal) were detected. This left 68 (73.1%)
      patients for follow-up, 33 (48.5%) of whom had patent branch vessels treated with
      the thrombogenic sponge. The median follow-up was 4 months (range 1 to 17),
      during which time no side branch endoleak was detected on surveillance CT scans
      in any of the 68 patients, which included all patients treated with the
      thrombogenic sponge technique and those in whom no patent side branches had been
      identified. CONCLUSIONS: We have demonstrated a safe and reliable method of
      preventing lumbar artery endoleaks following endovascular AAA repair.

PMID- 10893139
TI  - Endovascular repair of abdominal aortic aneurysm using a pararenal fenestrated
      stent-graft.
AB  - PURPOSE: To report an unusual case of endovascular abdominal aortic aneurysm
      (AAA) exclusion in which a fenestrated stent-graft was used to seal a proximal
      Type I endoleak. METHODS AND RESULTS: An 84-year-old man with a 6.0-cm AAA
      underwent an aortomonoiliac aneurysm exclusion procedure that was complicated by
      a proximal endoleak. Because the patient had no right kidney, an additional stent
      graft was designed to cover the right renal artery stump while preserving left
      renal perfusion through a fenestration in the graft material. This approach was
      successful in obliterating the endoleak around the proximal attachment site, but
      flow through the lumbar arteries remained. CONCLUSIONS: The use of a fenestrated
      stent-graft is feasible, but the type of fenestration in this case has limited
      applicability owing to the rarity of patients with suitable anatomy.

PMID- 10893140
TI  - Response of renal and femoropopliteal arteries to Palmaz stent implantation
      assessed with intravascular ultrasound.
AB  - PURPOSE: To establish the processes responsible for late lumen loss in renal and
      femoropopliteal Palmaz stents using intravascular ultrasound (IVUS). METHODS: The
      first 7 consecutive patients treated with stents for renal (n = 4) and
      femoropopliteal (n = 3) arterial occlusive disease were studied with IVUS
      immediately after angiographically successful stent placement (< 10% residual
      stenosis) and periodically during follow-up. Images of both stent edges and the
      most stenotic site inside the stent at followup were matched to the same cross
      sections captured immediately after stent placement for quantitative analysis.
      RESULTS: Late lumen loss in renal artery stents at 5 to 34 months was
      considerably less than in femoropopliteal stents (17% versus 62%, respectively).
      In the renal location, late lumen loss (3.0 +/- 1.3 mm2) was due to neointimal
      hyperplasia, whereas stent area remained unchanged (3% decrease). Late lumen loss
      (7.4 +/- 8.2 mm2) in femoropopliteal stents was due to neointimal hyperplasia and
      stent area reduction (26%). Overall, in both types of arteries, neointimal
      development and stent area reduction were larger at the most stenotic site than
      at the stent edges. CONCLUSIONS: These data suggest that there may be differences
      between renal and femoropopliteal arteries in the extent of hyperplastic response
      to stents.

PMID- 10893141
TI  - Clinical experience with superior vena caval Greenfield filters.
AB  - PURPOSE: To evaluate the results of superior vena caval (SVC) Greenfield filters
      in patients at risk for pulmonary embolism (PE) secondary to upper extremity deep
      venous thrombosis (UEDVT). METHODS: Over a 46-month period, 26 patients (10 men,
      mean age 67 years, range 25 to 89) with UEDVT in whom anticoagulation was
      contraindicated (n = 22) or ineffective in preventing recurrent PE or extension
      of the thrombus (n = 4) were treated with placement of SVC Greenfield filters.
      RESULTS: One SVC filter was misplaced into the innominate vein but left in place;
      this vein remains patent after 2 months without evidence of filter migration.
      Follow-up ranged from 10 days to 46 months (mean 7.8 months). Fifteen (58%)
      patients died inhospital of causes unrelated to the SVC filter or recurrent
      thromboembolism (mean time to death 36 days). Of the 11 survivors, follow-up
      ranged from 1 to 38 months (mean 22). Sequential chest roentgenograms in 9 (82%)
      patients revealed no filter migration or displacement. No evidence of PE was
      found in any of the survivors over the course of follow-up. CONCLUSIONS:
      Insertion of SVC Greenfield filters is a safe and feasible therapy to prevent
      recurrent thromboembolism in patients with UEDVT who are refractory to or
      inappropriate for anticoagulation therapy.

PMID- 10893142
TI  - Concurrent multivessel stenting in a patient with multifocal arterial disease.
AB  - PURPOSE: To report the concurrent endovascular treatment of multiple stenoses in
      different vascular territories. METHODS AND RESULTS: A 45-year-old male presented
      with an aortic arch syndrome, renovascular hypertension, and Leriche syndrome.
      Intra-arterial digital arteriography disclosed occlusion of the left subclavian
      artery and stenoses in the left common carotid artery (CCA), the right CCA at the
      bifurcation, the left renal artery, and both iliac arteries. In a single
      procedure, the patient received 5 stents in 2 carotid, 1 renal, and 2 iliac
      arteries. At 3-month follow-up, color flow duplex imaging confirmed continued
      patency of all stented arteries. CONCLUSIONS: This case illustrates the
      feasibility, safety, and cost effectiveness of treating multivessel stenoses
      using a single-session endovascular approach executed by experienced
      interventionists.

PMID- 10893143
TI  - Aorto-left renal vein fistula: is there a place for endovascular management?
AB  - PURPOSE: To describe the endovascular treatment of an aorto-left renal vein
      fistula. METHODS AND RESULTS: A 77-year-old man with multiple comorbidities
      presented with low back pain, hematuria, cyanosis, and a pulsatile abdominal
      mass. Imaging confirmed a 7-cm abdominal aortic aneurysm with a contained rupture
      into the left renal vein. Owing to the patient's high surgical risk, a Talent
      Endoluminal Stent-Graft was implanted to satisfactorily exclude the aneurysm.
      Hemodynamic stability and normal renal function were restored; however, continued
      perfusion of the sac prompted an attempt to percutaneously repair the renal vein
      defect. This effort failed, so open laparotomy was necessary. CONCLUSIONS:
      Although total endovascular management was not successful in this case, the
      initial use of a minimally invasive approach allowed the patient's clinical
      status to improve and lower the risk of subsequent surgery.

PMID- 10893144
TI  - Aortocaval fistula: a challenge for endovascular management.

PMID- 10893145
TI  - Endovascular repair of an aortoenteric fistula in a high-risk patient.
AB  - PURPOSE: To describe the endovascular repair of an aortoenteric fistula in a high
      risk patient. METHODS AND RESULTS: A Vanguard tube stent-graft was deployed at
      the upper anastomotic suture line of a secondary aortoenteric fistula,
      successfully sealing the communication between the aorta and the third part of
      the duodenum without occlusion of the renal arteries. CONCLUSIONS: Endovascular
      stent-graft repair of aortoenteric fistulae is possible, but further evaluation
      of this technique will determine its role in the management of this complication.

PMID- 10893146
TI  - Carotid stenting using radial artery access.

PMID- 10893147
TI  - Current knowledge on the structural proteins of porcine reproductive and
      respiratory syndrome (PRRS) virus: comparison of the North American and European
      isolates.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) belongs to the
      recently recognized Arteriviridae family within the genus Arterivirus, order
      Nidovirales, which also includes equine arteritis virus (EAV), lactate
      dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV).
      Mature viral particles are composed of an envelope 50-72 nm in diameter, with an
      isometric core about 20-30 nm enclosing a linear positive-stranded RNA genome of
      approximately 15 kb. The virions are assembled by the budding of preformed
      nucleocapsids into the lumen of the smooth endoplasmic reticulum and/or Golgi
      apparatus. The mature virions are then released by exocytosis. The viral genome
      contains eight open reading frames (ORFs) which are transcribed in cells as a
      nested set of subgenomic mRNAs. The ORF1a and ORF1b situated at the 5'end of the
      genome represent nearly 75% of the viral genome and code for proteins with
      apparent replicase and polymerase activities. The major structural proteins
      consist of a 25 kDa envelope glycoprotein (GP5), an 18-19 kDa unglycosylated
      membrane protein (M), and a 15 kDa nucleocapsid (N) protein, encoded by ORFs 5, 6
      and 7, respectively. The N protein is the more abundant protein of the virion and
      is highly antigenic, which therefore makes it a suitable candidate for the
      detection of virus-specific antibodies and diagnosis of the disease. Four to five
      domains of antigenic importance have been identified for the N protein, a common
      conformational antigenic site for European and North American strains being
      localized in the central region of the protein. In cells and virions, both M and
      GP5 occur in heterodimeric complexes linked by disulfide bonds. The expression
      products of ORFs 2 and 4 are also incorporated into virus particles as additional
      minor membrane-associated glycoproteins designated as GP2 and GP4, with M(r) of
      29 and 31 kDa, respectively. The structural nature of the ORF3 product, a highly
      glycosylated protein with an apparent M(r) of 42 kDa, is still being debated, in
      view of the apparently conflicting data on its presence in virus particles.
      Nonetheless, the GP3 of North American and European strains has been shown to be
      antigenic, providing protection for piglets against PRRSV infection in the
      absence of a noticeable neutralizing humoral response. Pigs exposed to the native
      form of GP5 by means of DNA immunization develop specific neutralizing and
      protecting antibodies. The GP5 is involved in antigenic variability, apoptosis,
      and possibly antibody-dependent enhancement phenomena. The GP4 also possesses
      antigenic determinants that trigger the immune system to produce neutralizing
      antibodies. Each of the PRRSV structural proteins carries common and type
      specific antigenic determinants that permit the ability to differentiate between
      European and North American strains. The potential use of the PRRSV structural
      proteins in subunit recombinant-type vaccines is also discussed.

PMID- 10893148
TI  - Soil-borne rye mosaic and European wheat mosaic virus: two names for a furovirus
      with variable genome properties which is widely distributed in several cereal
      crops in Europe.
AB  - PCR and nucleotide sequence analyses have revealed that Soil-borne rye mosaic
      furovirus (SBRMV) which we have recently described is widely distributed in
      Europe. In Northern Germany, Poland and Denmark the virus affects mainly rye and
      triticale, but in France and Italy it is wheat which becomes infected. The
      partial RNA 1 and RNA 2 sequences which were determined for the various SBRMV
      sources form several clusters, but so far no correlation between molecular
      differences and the type of host which becomes infected under natural conditions
      was detected. European wheat mosaic furovirus which was recently described by
      Diao et al. (1999) [Virology 261: 331-339] is closely related to a French source
      of SBRMV.

PMID- 10893149
TI  - Variability and molecular typing of the woody-tree infecting prunus necrotic
      ringspot ilarvirus.
AB  - The 3'-part of the movement protein gene, the intergenic region and the complete
      coat protein gene of sixteen isolates of Prunus necrotic ringspot virus (PNRSV)
      from five different host species from the Czech Republic were sequenced in order
      to search for the bases of extensive variability of viroses caused by this
      pathogen. According to phylogenetic analyses all the 46 isolates sequenced to
      date split into three main groups, which correlated to a certain extend with
      their geographic origin. Modelled serological properties showed that all the new
      isolates belong to one serotype.

PMID- 10893150
TI  - Antigenic diversity of Norwalk-like viruses: expression of the capsid protein of
      a genogroup I virus, distantly related to Norwalk virus.
AB  - The gene encoding the capsid protein of a genogroup I Norwalk-like virus (NLV)
      (Hu/NLV/Stav/95/Nor) was cloned and expressed in insect cells using a baculovirus
      vector. The His-tagged recombinant capsid protein (rStav) was antigenic and
      immunogenic, showed an apparent molecular weight of approximately 68 kD in
      protein gels, and was only soluble under denaturing conditions. The amino acid
      sequence of the rStav protein showed 65-88% similarity to capsid protein
      sequences from other genogroup I NLV and was most closely related to Desert
      Shield virus. Norwegian recruit sera were tested for antibodies against rStav by
      Western blotting (rStav WB). The sera had previously been tested for antibodies
      against a recombinant Norwalk virus capsid protein in an ELISA (rNV ELISA).
      Several rNV ELISA-negative sera showed a positive response in the rStav WB,
      indicating that the use of antigens representing different stains may be
      necessary when screening sera for antibodies against genogroup I NLV.

PMID- 10893152
TI  - Temporal and subcellular localization of infectious pancreatic necrosis virus
      structural proteins.
AB  - The temporal subcellular localization of the structural proteins VP2 and VP3 of
      infectious pancreatic necrosis virus was analyzed with monoclonal antibodies
      conjugated with fluorochromes. Early in the infection both proteins were
      colocalized in the cytosol, at later times, VP2 was visualized as inclusion
      bodies around the nuclei of the cells and, sometimes, it was found in elongated
      tubular structures that might correspond to the type I tubules seen in cells
      infected with another Birnavirus. As VP2 is a glycosylated protein we determined
      its subcellular localization compared with that of ER and Golgi probes. These
      results suggest that VP2 is glycosylated freely in the cytoplasm.

PMID- 10893151
TI  - Comparative sequence analysis of the VP7 genes of G6, G8 and G10 bovine group A
      rotarviruses and further characterization of G6 subtypes.
AB  - We previously reported the relatively high prevalence (15%) of bovine G6 subtypes
      (G6s) in the field using RT-PCR and restriction fragment length polymorphism
      (RFLP) analysis (Chang et al., Arch. Virol. 141: 1727-39). In the present study,
      we report the nucleotide and antigenic characterization of a G6s strain (C-8336).
      We also sequenced the VP7 genes of four additional bovine rotavirus (BRV)
      strains: another G6s (MC27), G6 (IND), G8 (C-8008) and G10 (2292B) and compared
      these with other bovine and human rotavirus strains. The C-8336 and MC27 strains
      were confirmed as P[11]G6s by RT-PCR and RFLP analysis. The VP7 genes of the C
      8336 and MC27 strains showed high homology to each other (approximately 98%) and
      with other bovine G6s strains (greater than 95% homology in nucleotide and amino
      acid sequence with KN-4[P[11]G6s]) and also showed lower, but substantial
      sequence homology with human G6s strains and prototype G6 BRV (79-87% in
      nucleotide and 88-91% in amino acid). Serologic analysis of the cell culture
      adapted C-8336 strain showed that it was neutralized by a G6 monoclonal antibody
      (MAb IC3) to similar titers as the reference NCDV and IND G6 strains. In two-way
      cross-neutralization tests, strain C-8336 showed 4- to 16-fold differences in
      antibody titers with NCDV and IND G6 BRV. Moreover polyclonal antiserum against
      strain C-8336 neutralized the NCDV and IND strains weakly. Genetic variability
      was also observed among G8 and G10 bovine and human group A rotaviruses: the VP7
      genes of the bovine C-8008 (P[5]G8) and 2292 B (P[11]G10) strains showed from 10
      to 17% nucleotide divergence with those of Cody 1801 (P[1]G8, bovine), A5
      (P[1]G8, bovine), 69M (P[10]G8, human) and Hal 1166 (P[14]G8, human), and
      I321(P[11]G10, human) and MC35 (P[14]G10, human) rotaviruses, respectively. The
      divergence of VP7 genes among bovine and human G6, G8 and G10 strains appears
      related to host species origin and their combination with VP4 (P type). The data
      presented in this report confirms the genetic variability among homotypic bovine
      and human strains and highlights the importance of continued monitoring of BRV G
      and P types circulating in the field for the future development and monitoring of
      effective vaccines.

PMID- 10893153
TI  - The presence of cross-reactive antibodies to rabbit haemorrhagic disease virus in
      Australian wild rabbits prior to the escape of virus from quarantine.
AB  - Sera collected from Australian wild rabbits prior to the escape of rabbit
      haemorrhagic disease virus (RHDV) from Wardang Island were examined for RHDV
      antibodies using purified recombinant capsid protein VP60 expressed from
      baculovirus. A VP60-based indirect ELISA showed that 196 of 392 wild rabbit sera
      reacted (OD(450) >0.15) with VP60. Twenty sera (OD(450) ranging from 0.15-2.47),
      randomly chosen from the 196 positive sera, recognized the 64 kDa VP60 in Western
      blot analysis, indicating that the reactivity detected in ELISA is indeed
      specific to the VP60 antigen. In a separate study, sera of 23 rabbits from an RHD
      free area after the escape of RHDV were tested by ELISA and 21 of the 23 rabbits
      were found to be positive. When these rabbits were challenged with a lethal dose
      of RHDV, 11 out of the 23 rabbits survived. The presence of RHDV-protective
      antibodies in some of these rabbits suggested that they had been exposed to a pre
      existing non-virulent rabbit calicivirus closely related to RHDV. These results
      highlight the need to study the prevalence of, and to characterize, this viral
      agent in order to effectively control rabbit populations in Australia and New
      Zealand.

PMID- 10893154
TI  - Isolation of an attenuated myxoma virus field strain that can confer protection
      against myxomatosis on contacts of vaccinates.
AB  - Twenty MV strains obtained from a survey of field strains currently circulating
      throughout Spain were analyzed for their virulence and horizontal spreading among
      rabbits by contact transmission. A virus strain with suitable characteristics to
      be used as a potential vaccine against myxomatosis in wild rabbit populations was
      selected. Following inoculation, the selected MV strain elicited high levels of
      MV specific antibodies and induced protection of rabbits against a virulent MV
      challenge. Furthermore, the attenuated MV was transmitted to 9 out of 16
      uninoculated rabbits by contact, inducing protection against myxomatosis.

PMID- 10893155
TI  - Antigenic and sequence heterogeneity of infectious bursal disease virus strains
      isolated in Australia.
AB  - Six recently isolated field strains of infectious bursal disease virus (IBDV)
      were compared to vaccine strains at the antigenic and genetic level to ascertain
      the level of heterogeneity among Australian IBDV strains. Five strains, 01/94,
      02/95, 03/95, 04/95 and 08/95, isolated at four locations in the state of
      Victoria, were antigenic variants. They failed to react with monoclonal
      antibodies directed against two different epitopes on the VP2 protein which were
      present in vaccine strains and one field isolate (06/95) from the state of New
      South Wales. Serum neutralization tests confirmed that these strains were
      antigenic variants as they were of a different subtype to that of vaccine
      strains. Sequence comparison of the hypervariable region of the VP2 proteins
      showed that the five Victorian strains had between 13 and 16 amino acid
      substitutions in comparison with vaccine strains. Four to six of these
      substitutions were in the two hydrophilic domains previously identified as being
      of importance in the formation of protective virus neutralizing antibodies.
      Comparison of these five variants to those isolated previously in the USA
      revealed little similarity at both the antigenic and genetic level. Phylogenetic
      analysis showed that Australian IBDV strains belong to a separate and distinct
      genetic group which is considerably heterogeneous. Overall the results indicate
      that the current Australian IBDV situation resembles that seen in the USA, with
      the existence of classical and variant IBDV strains, but neither the classical
      nor the variant strains found in Australia are closely related to those prevalent
      in the USA.

PMID- 10893156
TI  - Nucleotide sequence and synthesis of infectious RNA from cloned cDNA of broad
      bean wilt virus 2 RNA 2*.
AB  - The complete nucleotide sequence of broad bean wilt virus -2 (BBWV-2) RNA 2 was
      determined. The sequence is 3593 nucleotides in length, and contains a single
      open reading frame which has the potential to encode a 119 kDa polyprotein.
      Direct amino acid sequencing of the virus coat proteins suggests that the
      polyprotein is processed to produce three proteins, 52 kDa, 44 kDa and 22 kDa in
      size. A comparison of several fabaviruses in terms of nucleotide sequence and
      amino acid sequences showed that BBWV-2 isolates display high sequence identity.
      A full-length cDNA constructed under the control of the T7 promoter could be
      successfully transcribed to produce biologically active RNA. This is the first
      report on generating infectious transcripts of BBWV-2 RNA 2.

PMID- 10893157
TI  - pUL25 immunolocalization in human cytomegalovirus-infected and gene-transfected
      cells.
AB  - By means of confocal and electron microscope immunocytochemistry we have studied
      the localization of a recently described structural protein (pUL25) of human
      cytomegalovirus, in both infected cells and in cells transiently transfected with
      UL25. pUL25 localization in infected cells was observed in typical cytoplasmic
      structures characterized by a very electrondense texture previously reported to
      accumulate other tegument proteins. At the virion level pUL25 seems to localize
      at the interface between the tegument and the capsid of both intracytoplasmic and
      extracellular virions. In UL-25-transfected cells, pUL25 has been found in
      characteristic para-crystalline cytoplasmic aggregates, suggesting its intrinsic
      ability to aggregate in a regular subunit pattern.

PMID- 10893158
TI  - An epitope on the adenovirus fibre tail is common to all human subgroups.
AB  - A group specific linear epitope with the sequence -FNPVY- was detected in the
      tail region of the adenovirus fibre by using a monoclonal antibody (Mab) and
      selection with a hexapeptide phage expression library. A synthetic peptide with
      sequence DTFNPVYPYDTE from adenovirus type 2 (Ad2) was shown by preincubation
      with the Mab to block its binding to fibre. A biotinylated form of this peptide
      bound to the monomeric fibre and not to the dimeric and trimeric forms. On the
      other hand the monoclonal antibodies bound to the monomeric, dimeric and trimeric
      forms of the fibre.

PMID- 10893159
TI  - The internal rotavirus protein VP6 primes for an enhanced neutralizing antibody
      response.
AB  - We studied in the rotavirus system whether the internal protein VP6 could prime
      for an enhancement in the production of neutralizing antibodies (NeuAb) against
      the external proteins, VP7 and VP4. It was found that BALB/c mice immunized with
      recombinant YM VP6 protein, and challenged i.p. with a heterologous rotavirus had
      an increase in the production of serum NeuAb compared to the control. This
      response was both homotypic and heterotypic, and involved an increase of NeuAb
      belonging to the IgM and IgG isotypes. Mice immunized with the recombinant VP6
      and challenged orally with infectious murine rotavirus cleared the infection one
      day earlier than the control not immunized with VP6, and showed a small increase
      of total fecal anti-rotavirus IgA. The results suggest that the T-helper (Th)
      cells specific for VP6 can provide cognate help to B cells specific for
      neutralizing epitopes on the VP7 and/or VP4 molecules, and that this help can be
      heterotypic. Finally, we provide evidence that this phenomenon may be happening
      during infection.

PMID- 10893160
TI  - Site-directed mutagenesis of Autographa californica nucleopolyhedrovirus (AcNPV)
      polyhedrin: effect on polyhedron structure.
AB  - Amino acids Lys34, His36, and Phe37 were substituted by PCR-mediated, site
      directed mutagenesis for three Trp's in the AcNPV polyhedrin sequence. Phase
      contrast microscopy revealed refringent, amorphous polyhedra in the nuclei of
      infected cells. Electron microscopy confirmed a great variation in form and size
      of the mutated polyhedra. Although crystallization of the mutated polyhedrin
      occurred, it was irregular within each polyhedron. Virion occlusion was also
      severely affected. Virions were partially occluded, or only one virion was
      occluded per polyhedron. Results suggest that the substitution of these three
      amino acids affected the morphology of polyhedra, the uniformity of
      crystallization within each polyhedron, and the virion occlusion.

PMID- 10893161
TI  - Coat protein sequence comparisons of three Medican isolates of papaya ringspot
      virus with other geographical isolates reveal a close relationship to American
      and Australian isolates.
AB  - The coat protein gene of the papaya ringspot virus was cloned and sequenced in
      three Mexican isolates (two from Veracruz, and one from Chiapas). The sequences
      of these viral isolates were compared to those of eleven isolates from other
      parts of the world. They had higher similarity to isolates from Australia and the
      United States than to Asian isolates. A region of about one hundred nucleotides
      neighboring the putative aphid transmission triplet of the coat protein,
      contained repeats of an EK (glutamic acid-lysine) motif in all the sequences. The
      bearing of this region on the genetic relationships and geographical distribution
      of the isolates is analyzed and discussed.

PMID- 10893162
TI  - Restriction endonuclease analysis of the genome of two Italian caprine
      herpesvirus 1 strains.
AB  - Two caprine herpesvirus (CpHV.1) strains isolated in two goat flocks in southern
      Italy were compared with E/CH and McK/US reference CpHV.1 strains by restriction
      endonuclease analysis. BamHI, KpnI, NotI and PstI restriction enzymes were used.
      With these enzymes McK/US strain was clearly differentiated from the others. KpnI
      and NotI digestion resulted in unique patterns for all four strains. Restriction
      enzyme analysis might be a useful method to distinguish CpHV.1 isolated from
      animals and provide a basis for further epidemiological studies of the CpHV.1
      infection.

PMID- 10893163
TI  - Absence of evidence for porcine circovirus type 2 in cattle and humans, and lack
      of seroconversion or lesions in experimentally infected sheep.
AB  - No antibodies to porcine circovirus type 2 were detected in sera from cattle,
      sheep and humans. Experimental infection of lambs with this virus failed to
      produce lesions or seroconversion.

PMID- 10893164
TI  - Level of energy intake affects the estrous cycle in Sundevall's jird (Meriones
      crassus).
AB  - Effects of energy intake on the estrous cycle of the desert gerbillid,
      Sundevall's jird (Meriones crassus; 80 g; n=22) were studied. Females were
      offered either maintenance or below maintenance levels of millet seeds and ad
      lib. Atriplex halimus leaves and stems; drinking water was not available. Vaginal
      smears were used to determine sexual stage. We hypothesized that the estrous
      cycle ceases at low levels of energy intake and commences when sufficient energy
      is available. Females lost body mass linearly with a decrease in metabolizable
      energy intake. Estrous cycle averaged 4.46 d at maintenance energy intake but
      increased to an average of 7.81 d at 70% of maintenance energy intake. A
      cessation of the cycle occurred at an energy intake below 70% of maintenance
      requirements, which resulted in a body mass loss of more than 1% per day. More
      variability in the length of the different stages of the cycle was found with
      lower levels of energy intake. When offered ad lib. millet seeds and A. halimus
      (n=14), recovery to the normal cycle was attained within 10 d by 43% of the
      females and within 16 d by the rest of the females. Recovery time was longest in
      females that previously had the lowest energy intake. We concluded that the
      estrous cycle of M. crassus is sensitive to energy intake. With restricted energy
      intake, the estrous cycle and reproductive activities cease but can be restored
      with provision of adequate energy. This strategy ensures that reproduction occurs
      when conditions of food availability and body condition of the females are
      favorable.

PMID- 10893165
TI  - Metabolic adaptations of overwintering European common lizards (Lacerta
      vivipara).
AB  - The European common lizard Lacerta vivipara, a reptile of cold-temperate
      climates, provides us an interesting model of low-temperature adaptation. Indeed
      its unique cold-hardiness strategy, which employs both freeze tolerance and
      freeze avoidance, may be seen as the primary reason for its large distribution,
      which extends from Spain to beyond the Arctic circle. To study the metabolism
      supporting this capacity, we used three techniques: two techniques of calorimetry
      (oxygen consumption and thermogenesis) and nuclear magnetic resonance
      spectroscopy. These techniques were used to examine the metabolic balance and the
      different molecular pathways used between three different periods through the
      year (September, January, and May). The results show a significant 20%
      augmentation of winter anaerobic metabolism compared to other periods of the
      year. This is mainly because of an activation of the lactic fermentation pathway
      leading to an increase of lactate concentration (>34% in winter). Furthermore,
      glucose, which increases some 245% in winter, is used as antifreeze and metabolic
      substrate. Furthermore, this study provides evidence that the physiological
      adaptations of the common lizard differ from those of other ectotherms such as
      Rana sylvatica. Concentrations of alanine and glycerol, commonly used as
      antifreeze by many overwintering ectotherms, do not increase during winter.

PMID- 10893166
TI  - Growth and metabolism in the embryonic white-spotted bamboo shark, Chiloscyllium
      plagiosum: comparison with embryonic birds and reptiles.
AB  - Birds and reptiles have been important models for studying the energetics of
      embryonic development. Studies on these groups reveal three metabolic patterns:
      an exponential increase in metabolism with embryo age, a sigmoidal increase with
      age, or a sigmoidal increase followed by a decrease before hatching. Models
      developed to explain avian metabolic patterns and developmental costs partition
      total costs between growth and maintenance. To test the generality of these
      models, we examined embryonic energetics of the oviparous white-spotted bamboo
      shark Chiloscyllium plagiosum. Oviparous sharks must actively ventilate during
      development, which could increase their development costs relative to birds and
      reptiles. Our results demonstrated that bamboo shark embryos have a peaked
      metabolic pattern and sigmoidal increase in body mass similar to ratites,
      crocodilians, and some turtles. The total cost of development was higher in
      bamboo sharks than in reptiles and many birds. However, calculations reveal that
      the high cost of bamboo shark development can be explained by the relatively long
      incubation time rather than the additional cost of muscular movement. Finally, an
      avian model can reasonably describe shark embryonic metabolism, suggesting that
      movement costs do not significantly alter the metabolic pattern during
      development.

PMID- 10893167
TI  - Effects of cortisol and salinity challenge on water balance in developing larvae
      of tilapia (Oreochromis mossambicus).
AB  - Effects of exogenous cortisol on drinking rate and water content in developing
      larvae of tilapia (Oreochromis mossambicus) were examined. Both freshwater- and
      seawater-adapted larvae showed increases in drinking rates with development.
      Drinking rates of seawater-adapted larvae were about four- to ninefold higher
      than those of freshwater-adapted larvae from day 2 to day 5 after hatching.
      Seawater-adapted larvae showed declines in drinking rate and water content at 4
      and 14 h, respectively, after immersion in 10 mg L(-1) cortisol. In the case of
      freshwater-adapted larvae, the drinking rate decreased after 8 h of cortisol
      immersion, while the water content did not show a significant change even after
      32 h of cortisol immersion. In a subsequent experiment of transfer from
      freshwater to 20 ppt (parts per thousand, salinity) seawater, immersion in 10 mg
      L(-1) cortisol for 8-24 h enhanced the drinking rate in larvae at 4 h after
      transfer, but no significant difference was found in water contents between
      cortisol-treated and control groups following transfer. These results suggest
      that cortisol is involved in the regulation of drinking activity in developing
      tilapia larvae.

PMID- 10893168
TI  - Lactic acid buffering by bone and shell in anoxic softshell and painted turtles.
AB  - We tested two hypotheses: first, that the inferior anoxia tolerance of the
      softshell turtle, Apalone spinifera, compared to the western painted turtle,
      Chrysemys picta bellii, is related to its less mineralized shell, and second,
      that turtle bone, like its shell, stores lactate during prolonged anoxia. Lactate
      concentrations of blood, hindlimb bone, and shell were measured on normoxic
      Apalone and Chrysemys and after anoxic submergence at 10 degrees C for 2 and 9 d,
      respectively. Blood and shell concentrations of Ca(2+), Mg(2+), Na(+), K(+), and
      inorganic phosphate (P(i); for shell only) were also measured. Because a
      preliminary study indicated lactate distribution in Chrysemys throughout its
      skeleton during anoxia at 20 degrees C, we used hindlimb bones as representative
      skeletal samples. Apalone shell, though a similar percentage of body mass as
      Chrysemys shell, had higher water content (76.9% vs. 27.9%) and only 20%-25% as
      much Ca(2+), Mg(2+), CO(2), and P(i). When incubated at constant pH of 6.0 or
      6.5, Apalone shell powder released only 25% as much buffer per gram wet weight as
      Chrysemys shell. In addition, plasma [Ca(2+)] and [Mg(2+)] increased less in
      Apalone during anoxia at an equivalent plasma lactate concentration. Lactate
      concentrations increased in the shell and skeletal bone in both species. Despite
      less mineralization, Apalone shell took up lactate comparably to Chrysemys. In
      conclusion, a weaker compensatory response to lactic acidosis in Apalone
      correlates with lower shell mineralization and buffer release and may partially
      account for the poorer anoxia tolerance of this species.

PMID- 10893169
TI  - Effects of maternal identity and incubation temperature on snapping turtle
      (Chelydra serpentina) metabolism.
AB  - Individual variation in physiological traits may have important consequences for
      offspring survivorship and adult fitness. Variance in offspring phenotypes is due
      to interindividual differences in genotype, environment, and/or maternal effects.
      This study examined the contributions of incubation environment, maternal
      effects, and clutch identity to individual variation in metabolic rates in the
      common snapping turtle, Chelydra serpentina. We measured standard metabolic rate,
      as determined by oxygen consumption, for 246 individuals representing 24 clutches
      at 15 degrees and 25 degrees C, and we measured standard metabolic rates
      additionally for 34 individuals at 20 degrees and 30 degrees C. Standard
      metabolic rate for 34 snapping turtles measured at 15 degrees, 20 degrees, 25
      degrees, and 30 degrees C increased with increasing temperature. Mean standard
      metabolic rate for 246 individuals was 0.247 microL O(2) min(-1) g(-1) at 15
      degrees C and 0.919 microL O(2) min(-1) g(-1) at 25 degrees C. At 15 degrees C,
      mass at hatching, individual mass, and egg mass had no significant effects on
      metabolic rate, but at 25 degrees C, mass at hatching, individual mass, and egg
      mass did have significant effects on metabolic rate. Incubation temperature had
      no significant effect on metabolic rate at 15 degrees, but it did have a
      significant effect at 25 degrees C. Clutch identity had a significant effect on
      metabolic rate at both 15 degrees and 25 degrees C. Interindividual variation in
      standard metabolic rate due to incubation temperature, and especially clutch
      identity, could have large effects on energy budgets. Results suggest that there
      were both environmental and genetic effects on standard metabolic rate.

PMID- 10893170
TI  - Relationships between annual cycles of testosterone, corticosterone, and body
      condition in male red-spotted garter snakes, Thamnophis sirtalis concinnus.
AB  - Over a 2-yr period, we investigated the annual cycles of plasma testosterone and
      corticosterone and the relationships between these hormones and body condition in
      a wild population of male red-spotted garter snakes, Thamnophis sirtalis
      concinnus. In the 10 mo that were sampled, a peak in testosterone was observed in
      late summer during gametogenesis and declining through the spring breeding
      period. Corticosterone and testosterone cycles were positively correlated, in
      contrast to many vertebrates, suggesting the lack of a direct negative
      interaction between the two hormones. Body condition, defined as the residual of
      the regression of mass on snout-vent length, also cycled annually, with
      individuals being more robust during the summer than during the spring or fall.
      Individuals with a positive body condition had significantly lower plasma levels
      of corticosterone than did individuals with a negative body condition, supporting
      the energetic role of glucocorticoids. There was no relationship between body
      condition and testosterone. This study suggests that annual cycles of
      testosterone, corticosterone, and body condition can be associated with one
      another, and considering all three simultaneously is necessary to understand
      their control and function.

PMID- 10893171
TI  - Does gut function limit hummingbird food intake?
AB  - Many nectar-feeding bird species decrease food intake when sugar concentration in
      food is increased. This feeding response can be explained by two alternative
      hypotheses: compensatory feeding and physiological constraint. The compensatory
      feeding hypothesis predicts that if birds vary intake to maintain a constant
      energy intake to match energy expenditures, then they should increase intake when
      expenditures are increased. Broad-tailed hummingbirds were presented with sucrose
      solutions at four concentrations (292, 584, 876, and 1,168 mmol L(-1)) and
      exposed to two environmental temperatures (10 degrees and 22 degrees C). Birds
      decreased volumetric food intake in response to sugar concentration. However,
      when they were exposed to a relatively sudden drop in environmental temperature
      and, hence, to an acute increase in thermoregulatory energy expenditures, they
      did not increase their rate of energy consumption and lost mass. These results
      support the existence of a physiological constraint on feeding intake. A simple
      chemical reactor model based on intestinal morphology and in vitro measurements
      of sucrose hydrolysis predicted observed intake rates closely. This model
      suggests that intestinal sucrose hydrolysis rates were near maximal and, thus,
      may have imposed limits to sugar assimilation. Although sugar assimilation was
      high (95%), the proportions of excreted sucrose, glucose, and fructose found in
      excreta differed significantly. The monosaccharides glucose and fructose were
      about eight and three times more abundant than sucrose, respectively. Broad
      tailed hummingbirds are small high-altitude endotherms that face unpredictable
      weather and the energetic expense of premigratory fattening. Digestive processes
      have the potential to impose severe challenges to their energy budgets.

PMID- 10893172
TI  - An application of randomization for detecting evidence of thermoregulation in
      timber rattlesnakes (Crotalus horridus) from northwest Arkansas.
AB  - Most reptiles maintain their body temperatures within normal functional ranges
      through behavioral thermoregulation. Under some circumstances, thermoregulation
      may be a time-consuming activity, and thermoregulatory needs may impose
      significant constraints on the activities of ectotherms. A necessary (but not
      sufficient) condition for demonstrating thermoregulation is a difference between
      observed body temperature distributions and available operative temperature
      distributions. We examined operative and body temperature distributions of the
      timber rattlesnake (Crotalus horridus) for evidence of thermoregulation.
      Specifically, we compared the distribution of available operative temperatures in
      the environment to snake body temperatures during August and September. Operative
      temperatures were measured using 48 physical models that were randomly deployed
      in the environment and connected to a Campbell CR-21X data logger. Body
      temperatures (n=1,803) were recorded from 12 radiotagged snakes using temperature
      sensitive telemetry. Separate randomization tests were conducted for each hour of
      day within each month. Actual body temperature distributions differed
      significantly from operative temperature distributions at most time points
      considered. Thus, C. horridus exhibits a necessary (but not sufficient) condition
      for demonstrating thermoregulation. However, unlike some desert ectotherms, we
      found no compelling evidence for thermal constraints on surface activity.
      Randomization may prove to be a powerful technique for drawing inferences about
      thermoregulation without reliance on studies of laboratory thermal preference.

PMID- 10893173
TI  - Test for physiological limitation to nutrient assimilation in a long-distance
      passerine migrant at a Springtime stopover site.
AB  - During northward migration, blackcaps arrive at stopover sites in Israel's Negev
      Desert with reduced masses of organs that are important in food digestion and
      assimilation. Blackcaps that stay to refuel (largely on fruits) do not gain mass
      rapidly until after 3 d at the stopover site. We hypothesized that (1) it may
      take several days to rebuild these reduced organs, (2) during this recovery
      interval high feeding rates might not be possible, and (3) this could be the
      basis for the absence of immediate body mass gain in blackcaps at stopover sites.
      To test predictions from this hypothesis we used an established fasting protocol
      to create a group of blackcaps with reduced intestinal and liver mass compared
      with ad lib. fed controls. Migrants were captured and caged in the laboratory,
      where they were habituated to a fruit mash diet for 8 d. One experimental group
      was then fasted 2 d, one was fed at a restricted level (one-third ad lib. food
      intake) for 4 d, and one was held as ad lib.-fed controls. The fasted and
      restricted birds were then allowed to feed again ad lib. Birds that were
      experimentally fasted progressively increased their daily assimilation rate and
      achieved the highest rate (one-third higher than controls) 3 d after the end of
      their fast. Birds that were restricted achieved high rates immediately once ad
      lib. food was provided. Increased assimilation rate was achieved via hyperphagia
      and not increased assimilation efficiency. The response of the fasted birds
      supports the hypothesis that there may be physiological constraints to the rate
      of refueling during migratory stopover.

PMID- 10893174
TI  - Effects of reproductive condition, season, and site on selected temperatures of a
      viviparous gecko.
AB  - The relationship between thermal and reproductive biology is complex and poorly
      understood. We measured selected body temperatures (T(sel)) for the viviparous
      gecko Hoplodactylus maculatus. T(sel) was compared among pregnant females,
      nonpregnant females, and males from two sites: a cool site with biennially
      reproducing geckos and a warm site with annually reproducing geckos. T(sel) was
      measured at five times of day during three seasons and compared with microhabitat
      temperature (T(top)) and field body temperature (T(b)). T(sel) varied with time
      of day in all comparisons, and the effect of reproductive condition on T(sel)
      differed between sites and seasons. At both sites, when T(sel) differed between
      reproductive conditions, pregnant females had higher T(sel) than nonpregnant
      females and males. Stage of pregnancy affected the degree of elevation of T(sel).
      Measurements of microhabitat temperature and field T(b) showed that, even in the
      warmest season, geckos rarely had the opportunity to achieve T(sel) at the cool
      site but were able to do so at the warm site. The elevation of T(sel) with
      pregnancy is extreme in this species (up to 8 degrees C), which suggests that an
      increase in T(b) is critical to successful reproduction. Interactions between the
      effects of time of day, season, and reproductive condition on T(sel) must be
      considered in the assessment of thermoregulation in reptiles.

PMID- 10893175
TI  - The effects of acute and developmental temperature on burst swimming speed and
      myofibrillar ATPase activity in tadpoles of the Pacific tree frog, Hyla regilla.
AB  - The effects of acute and developmental temperature on maximum burst swimming
      speed, body size, and myofibrillar ATPase activity were assessed in tadpoles of
      the Pacific tree frog, Hyla regilla. Tadpoles from field-collected egg masses
      were reared in the laboratory at 15 degrees (cool) and 25 degrees C (warm). Body
      size, maximum burst swimming speed from 5 degrees to 35 degrees C, and tail
      myofibrillar ATPase activity at 15 degrees and 25 degrees C were measured at a
      single developmental stage. Burst speed of both groups of tadpoles was strongly
      affected by test temperature (P<0. 001). Performance maxima spanned test
      temperatures of 15 degrees -25 degrees C for the cool group and 15 degrees -30
      degrees C for the warm group. Burst speed also depended on developmental
      temperature (P<0.001), even after accounting for variation in body size. At most
      test temperatures, the cool-reared tadpoles swam faster than the warm-reared
      tadpoles. Myofibrillar ATPase activity was affected by test temperature
      (P<0.001). Like swimming speed, enzyme activity was greater in the cool-reared
      tadpoles than in the warm-reared tadpoles, a difference that was significant when
      assayed at 15 degrees C (P<0. 01). These results suggest a mechanism for
      developmental temperature effects on locomotor performance observed in other
      taxa.

PMID- 10893176
TI  - Gas transfer system in Alvinella pompejana (Annelida polychaeta, Terebellida):
      functional properties of intracellular and extracellular hemoglobins.
AB  - Alvinella pompejana is a tubicolous polychaete that dwells in the hottest part of
      the hydrothermal vent ecosystem in a highly variable mixture of vent (350 degrees
      C, anoxic, CO(2)- and sulfide-rich) and deep-sea (2 degrees C, mildly hypoxic)
      waters. This species has developed distinct-and specifically respiratory
      adaptations to this challenging environment. An internal gas exchange system has
      recently been described, along with the report of an intracellular coelomic
      hemoglobin, in addition to the previously known extracellular vascular
      hemoglobin. This article reports the structure of coelomic hemoglobin and the
      functional properties of both hemoglobins in order to assess possible oxygen
      transfer. Coelomocytes contain a unique monomeric hemoglobin with a molecular
      weight of 14,810+/-1.5 Da, as determined by mass spectrometry. The functional
      properties of both hemoglobins are unexpectedly very similar under the same
      conditions of pH (6.1-8.2) and temperature (10 degrees -40 degrees C). The oxygen
      affinity of both proteins is relatively high (P50=0.66 Torr at 20 degrees C and
      pH 7), which facilitates oxygen uptake from the hypoxic environment. A strong
      Bohr effect (Phi ranging from -0.8 to -1.0) allows the release of oxygen to
      acidic tissues. Such similar properties imply a possible bidirectional transfer
      of oxygen between the two hemoglobins in the perioesophagal pouch, a mechanism
      that could moderate environmental variations of oxygen concentration and maintain
      brain oxygenation.

PMID- 10893177
TI  - Thermoregulation by kangaroos from mesic and arid habitats: influence of
      temperature on routes of heat loss in eastern grey kangaroos (Macropus giganteus)
      and red kangaroos (Macropus rufus).
AB  - We examined thermoregulation in red kangaroos (Macropus rufus) from deserts and
      in eastern grey kangaroos (Macropus giganteus) from mesic forests/woodlands.
      Desert kangaroos have complex evaporative heat loss mechanisms, but the relative
      importance of these mechanisms is unclear. Little is known of the abilities of
      grey kangaroos. Our detailed study of these kangaroos' thermoregulatory responses
      at air temperatures (T(a)) from -5 degrees to 45 degrees C showed that, while
      some differences occur, their abilities are fundamentally similar. Both species
      show the basic marsupial characteristics of relatively low basal metabolism and
      body temperature (T(b)). Within the thermoneutral zone, T(b) was 36.3 degrees +
      or - 0.1 degrees C (X + or - SE) in both species, and except for a small rise at
      T(a) 45 degrees C, T(b) was stable over a wide range of T(a). Metabolic heat
      production was 25% higher in red kangaroos at T(a) -5 degrees C. At the highest
      T(a) (45 degrees C), both species relied on evaporative heat loss (EHL) to
      maintain T(b); both panting and licking were used. The eastern grey kangaroo
      utilised panting (76% of EHL) as the principal mode of EHL, and while this was so
      for red kangaroos, cutaneous evaporative heat loss (CEHL) was significant (40% of
      EHL). CEHL appeared to be mainly licking, as evidenced from surface temperatures.
      Both species utilised peripheral vascular adjustments to control heat flow, as
      indicated by changes in dry conductance (C(dry)). At lower temperatures, C(dry)
      was minimal, but it increased significantly at T(a) just below T(b) (33 degrees
      C); in these conditions, the C(dry) of red kangaroos was significantly higher
      than that of eastern grey kangaroos, indicating a greater reliance on dry heat
      loss. Under conditions where heat flows into the body from the environment (T(a)
      45 degrees C), there was peripheral vasoconstriction to reduce this inflow;
      C(dry) decreased significantly from the values seen at 33 degrees C in both
      kangaroos. The results indicated that, while both species have excellent
      thermoregulatory abilities, the desert red kangaroos may cope better with more
      extreme temperatures, given that they respond to T(a) 45 degrees C with lower
      respiratory evaporation than do the eastern grey kangaroos.

PMID- 10893178
TI  - Ventilatory accommodation of oxygen demand and respiratory water loss in
      kangaroos from mesic and arid environments, the eastern grey kangaroo (Macropus
      giganteus) and the red kangaroo (Macropus rufus).
AB  - We studied ventilation in kangaroos from mesic and arid environments, the eastern
      grey kangaroo (Macropus giganteus) and the red kangaroo (Macropus rufus),
      respectively, within the range of ambient temperatures (T(a)) from -5 degrees to
      45 degrees C. At thermoneutral temperatures (Ta=25 degrees C), there were no
      differences between the species in respiratory frequency, tidal volume, total
      ventilation, or oxygen extraction. The ventilatory patterns of the kangaroos were
      markedly different from those predicted from the allometric equation derived for
      placentals. The kangaroos had low respiratory frequencies and higher tidal
      volumes, even when adjustment was made for their lower basal metabolism. At Ta>25
      degrees C, ventilation was increased in the kangaroos to facilitate respiratory
      water loss, with percent oxygen extraction being markedly lowered. Ventilation
      was via the nares; the mouth was closed. Differences in ventilation between the
      two species occurred at higher temperatures, and at 45 degrees C were associated
      with differences in respiratory evaporative heat loss, with that of M. giganteus
      being higher. Panting in kangaroos occurred as a graded increase in respiratory
      frequency, during which tidal volume was lowered. When panting, the desert red
      kangaroo had larger tidal volumes and lower respiratory frequencies at equivalent
      T(a) than the eastern grey kangaroo, which generally inhabits mesic forests. The
      inference made from this pattern is that the red kangaroo has the potential to
      increase respiratory evaporative heat loss to a greater level.

PMID- 10893179
TI  - RecQ-like helicases: the DNA replication checkpoint connection.
AB  - The eukaryotic homologues of the Escherichia coli RecQ DNA helicase play
      conserved roles in the maintenance of genome stability. Results obtained in yeast
      and mammalian systems are beginning to form a coherent picture about what these
      helicases do to ensure normal cell division and why humans who lack these enzymes
      are cancer prone. Recent data suggest that the yeast enzyme Sgs1p, as well as two
      human homologues, which are encoded by the Bloom's and Werner's syndrome genes,
      function during DNA replication and possibly in a replication checkpoint specific
      to S phase.

PMID- 10893180
TI  - CAF-1 and the inheritance of chromatin states: at the crossroads of DNA
      replication and repair.
AB  - Chromatin is no longer considered to be a static structural framework for
      packaging DNA within the nucleus but is instead believed to be an interactive
      component of DNA metabolism. The ordered assembly of chromatin produces a
      nucleoprotein template capable of epigenetically regulating the expression and
      maintenance of the genome. Factors have been isolated from cell extracts that
      stimulate early steps in chromatin assembly in vitro. The function of one such
      factor, chromatin-assembly factor 1 (CAF-1), might extend beyond simply
      facilitating the progression through an individual assembly reaction to its
      active participation in a marking system. This marking system could be exploited
      at the crossroads of DNA replication and repair to monitor genome integrity and
      to define particular epigenetic states.

PMID- 10893181
TI  - Inhibiting proteasome activity causes overreplication of DNA and blocks entry
      into mitosis in sea urchin embryos.
AB  - The proteasome has been shown to be involved in exit from mitosis by bringing
      about destruction of mitotic cyclins. Here, we present evidence that the
      proteasome is also required for proper completion of S phase and for entry into
      mitosis in the sea urchin embryonic cleavage cycle. A series of structurally
      related peptide-aldehydes prevent nuclear envelope breakdown in their order of
      inhibitory efficacies against the proteasome. Their efficacies in blocking exit
      from S phase and exit from mitosis correlate well, indicating that the proteasome
      is involved at both these steps. Mitotic histone HI kinase activation and
      tyrosine dephosphorylation of p34(cdc2) kinase are blocked by inhibition of the
      proteasome, indicating that the proteasome plays an important role in the pathway
      that leads to embryonic p34(cdc2 )kinase activation. Arrested embryos continued
      to incorporate [(3)H]thymidine and characteristically developed large nuclei. Pre
      mitotic arrest can be overcome by treatment with caffeine, a manoeuvre that is
      known to override the DNA replication checkpoint. These data demonstrate that the
      proteasome is involved in the control of termination of S phase and consequently
      in the initiation of M phase of the first embryonic cell cycle.

PMID- 10893182
TI  - Membrane gamma-glutamyl transpeptidase activity of melanoma cells: effects on
      cellular H(2)O(2) production, cell surface protein thiol oxidation and NF-kappa B
      activation status.
AB  - The metabolism of glutathione by membrane-bound &ggr;-glutamyl transpeptidase
      (GGT) has been recently recognized as a basal source of hydrogen peroxide in the
      extracellular space. Significant levels of GGT activity are expressed by
      malignant tumours, and in melanoma cell lines they were found to correlate with
      the malignant behaviour. As hydrogen peroxide and other oxidants can affect
      signal transduction pathways at several levels, the present study was aimed to
      verify: (i) the occurrence of GGT-dependent production of hydrogen peroxide in
      melanoma cells; (ii) the effects of GGT-dependent prooxidant reactions on known
      redox-sensitive cellular targets, i.e. protein thiols, the nuclear transcription
      factor NF-kappa B and p53. Two melanoma Me665/2 cell clones, exhibiting traces of
      (clone 2/21) or high (clone 2/60) GGT activity, were studied. The occurrence of
      GGT-dependent production of hydrogen peroxide was apparent in 2/60 cells, in
      which it was accompanied by lower levels of cell surface protein thiols. In 2/60
      cells, GGT expression was also associated with higher levels of NF-kappa B
      activation, as compared to GGT-poor 2/21 cell clone. Indeed, stimulation or
      inhibition of GGT activity in 2/60 cells resulted in progressive activation or
      inactivation of NF-kappa B, respectively. An analysis of the p53 gene product
      indicated lack of protein expression in 2/60 cells, whereas a mutant protein was
      highly expressed in 2/21 cells. Taken together, these results indicate that the
      expression of GGT activity can provide melanoma cells with an additional source
      of hydrogen peroxide, and that such prooxidant reactions are capable to modify
      protein thiols at the cell surface level. In addition, GGT expression results in
      an up-regulation of the transcription factor NF-kappa B, which could explain the
      higher metastatic behaviour reported for GGT-rich melanoma cells as compared to
      their GGT-poor counterparts.

PMID- 10893183
TI  - Mammalian cell lines expressing functional RNA polymerase II tagged with the
      green fluorescent protein.
AB  - RNA polymerase II is a multi-subunit enzyme responsible for transcription of most
      eukaryotic genes. It associates with other complexes to form enormous
      multifunctional 'holoenzymes' involved in splicing and polyadenylation. We wished
      to study these different complexes in living cells, so we generated cell lines
      expressing the largest, catalytic, subunit of the polymerase tagged with the
      green fluorescent protein. The tagged enzyme complements a deficiency in tsTM4
      cells that have a temperature-sensitive mutation in the largest subunit. Some of
      the tagged subunit is incorporated into engaged transcription complexes like the
      wild-type protein; it both resists extraction with sarkosyl and is
      hyperphosphorylated at its C terminus. Remarkably, subunits bearing such a tag
      can be incorporated into the active enzyme, despite the size and complexity of
      the polymerizing complex. Therefore, these cells should prove useful in the
      analysis of the dynamics of transcription in living cells.

PMID- 10893184
TI  - Dynamic, Rho1p-dependent localization of Pkc1p to sites of polarized growth.
AB  - In eukaryotes, the Rho GTPases and their effectors are key regulators of the
      actin cytoskeleton, membrane trafficking and secretion, cell growth, cell cycle
      progression and cytokinesis. Budding yeast Pkc1p, a protein kinase C-like enzyme
      involved in cell wall biosynthesis and cytoskeletal polarity, is structurally and
      functionally related to the Rho-associated kinases (PRK/ROCK) of mammalian cells.
      In this study, localization of Pkc1p was monitored in live cells using a GFP
      fusion (Pkc1p-GFP). Pkc1p-GFP showed dynamic spatial and temporal localization at
      sites of polarized growth. Early in the cell cycle, Pkc1p-GFP was found at the
      pre-bud site and bud tips, becoming delocalized as the cell progressed further
      and finally relocalizing around the mother-daughter bud neck in an incomplete
      ring, which persisted until cell separation. Bud localization was actin-dependent
      but stability of Pkc1p-GFP at the neck was actin-independent, although
      localization at both sites required functional Rho1p. In addition, Pkc1p-GFP
      showed rapid relocalization after cell wall damage. These results suggest that
      the roles of Pkc1p in both polarized growth and the response to cell wall stress
      are mediated by dynamic changes in its localization, and suggest an additional
      potential role in cytokinesis.

PMID- 10893185
TI  - Slow muscle induction by Hedgehog signalling in vitro.
AB  - Muscles are composed of several fibre types, the precise combination of which
      determines muscle function. Whereas neonatal and adult fibre type is influenced
      by a number of extrinsic factors, such as neural input and muscle load, there is
      little knowledge of how muscle cells are initially determined in the early
      embryo. In the zebrafish, fibres of the slow twitch class arise from precociously
      specified myoblasts that lie close to the midline whereas the remainder of the
      myotome differentiates as fast myosin expressing muscle. In vivo evidence has
      suggested the Sonic Hedgehog glycoprotein, secreted from the notochord, controls
      the formation of slow twitch and fast twitch muscle fates. Here we describe an in
      vitro culture system that we have developed to test directly the ability of
      zebrafish myoblasts to respond to exogenous Sonic Hedgehog peptide. We find that
      Sonic Hedgehog peptide can control the binary cell fate choice of embryonic
      zebrafish myoblasts in vitro. We have also used this culture system to assay the
      relative activities of different Hedgehog-family proteins and to investigate the
      possible involvement of heterotrimeric G-proteins in Hedgehog signal
      transduction.

PMID- 10893186
TI  - Goosecoid suppresses cell growth and enhances neuronal differentiation of PC12
      cells.
AB  - In all vertebrate species, the homeobox gene goosecoid serves as a marker of the
      Spemann organizer tissue. One function of the organizer is the induction of
      neural tissue. To investigate the role of goosecoid in neuronal differentiation
      of mammalian cells, we have introduced goosecoid into PC12 cells. Expression of
      goosecoid resulted in reduced cell proliferation and enhanced neurite outgrowth
      in response to NGF. Expression of goosecoid led to a decrease in the percentage
      of S-phase cells and to upregulation of the expression of the neuron-specific
      markers MAP-1b and neurofilament-L. Analysis of goosecoid mutants revealed that
      these effects were independent of either DNA binding or homodimerization of
      Goosecoid. Coexpression of the N-terminal portion of the ets transcription factor
      PU.1, a protein that can bind to Goosecoid, repressed neurite outgrowth and
      rescued the proliferation of PC12 cultures. In contrast, expression of the bHLH
      transcription factor HES-1 repressed goosecoid-mediated neurite outgrowth without
      changing the proportion of S-phase cells. These results suggest that goosecoid is
      involved in neuronal differentiation in two ways, by slowing the cell cycle and
      stimulating neurite outgrowth, and that these two events are separately
      regulated.

PMID- 10893187
TI  - Assembly of multiple dystrobrevin-containing complexes in the kidney.
AB  - Dystrophin is the key component in the assembly and maintenance of the dystrophin
      associated protein complex (DPC) in skeletal muscle. In kidney, dystroglycan, an
      integral component of the DPC, is involved in kidney epithelial morphogenesis,
      suggesting that the DPC is important in linking the extracellular matrix to the
      internal cytoskeleton of kidney epithelia. Here, we have investigated the
      molecular architecture of dystrophin-like protein complexes in kidneys from
      normal and dystrophin-deficient mice. Using isoform-specific antibodies, we show
      that the different cell types that make up the kidney maintain different
      dystrophin-like complexes. These complexes can be broadly grouped according to
      their dystrobrevin content: beta-dystrobrevin containing complexes are present at
      the basal region of renal epithelial cells, whilst alpha-dystrobrevin-1
      containing complexes are found in endothelial and smooth muscle cells.
      Furthermore, these complexes are maintained even in the absence of all dystrophin
      isoforms. Thus our data suggest that the functions and assembly of the dystrophin
      like complexes in kidney differ from those in skeletal muscle and implicate a
      protein other than dystrophin as the primary molecule in the assembly and
      maintenance of kidney complexes. Our findings also provide a possible explanation
      for the lack of kidney pathology in Duchenne muscular dystrophy patients and mice
      lacking all dystrophin isoforms.

PMID- 10893188
TI  - The small GTPase Rab6B, a novel Rab6 subfamily member, is cell-type specifically
      expressed and localised to the Golgi apparatus.
AB  - Members of the Rab subfamily of small GTPases play an important role in the
      regulation of intracellular transport routes. Rab6A has been shown to be a
      regulator of membrane traffic from the Golgi apparatus towards the endoplasmic
      reticulum (ER). Here, we report on the identification of a Rab6 isoform, termed
      Rab6B. The corresponding full-length cDNA was isolated from a Caco-2 cell
      library. The deduced amino acid sequence showed 91% identity with the Rab6A
      protein and revealed that sequence divergence is dispersed over a large region of
      the COOH-terminal domain. Rab6B is encoded by an independent gene which is
      located on chromosome 3 region q21-q23. In contrast to Rab6A whose expression is
      ubiquitous, northern blot analysis, immunohistochemistry, and immunofluorescence
      demonstrated that Rab6B is expressed in a tissue and cell-type specific manner.
      Rab6B is predominantly expressed in brain and the neuroblastoma cell line SK-N
      SH. In brain, Rab6B was found to be specifically expressed in microglia,
      pericytes and Purkinje cells. Endogenous Rab6B localises to the Golgi apparatus
      and to ERGIC-53-positive vesicles. Comparable studies between Rab6A and Rab6B
      revealed distinct biochemical and cellular properties. Rab6B displayed lower GTP
      binding activities and in overexpression studies, the protein is distributed over
      Golgi and ER membranes, whereas Rab6A is more restricted to the Golgi apparatus.
      Since the GTP-bound form of Rab6B (Rab6B Q72L) does interact with all known Rab6A
      effectors, including Rabkinesin-6, the results suggest a cell-type specific role
      for Rab6B in retrograde membrane traffic at the level of the Golgi complex.

PMID- 10893189
TI  - Role of the cytoskeleton in rapid activation of CD11b/CD18 function and its
      subsequent downregulation in neutrophils.
AB  - When rolling adherent neutrophils are stimulated, they rapidly immobilize through
      activation of integrin CD11b/CD18, and then modulate attachment through this
      integrin to allow migration. We investigated links between cytoskeletal
      rearrangement and changes in function of integrin CD11b/CD18 in neutrophils
      stimulated with formyl peptide (fMLP). Neutrophils treated with the actin
      polymerizing agent jasplakinolide became rolling adherent on monolayers of
      activated platelets, but could not use CD11b/CD18 to become immobilised when fMLP
      was perfused over them. If treated with jasplakinolide after fMLP, the cells
      stopped migrating but could not detach when fMLP was removed. Jasplakinolide did
      not inhibit changes in intracellular Ca(2+) seen after fMLP treatment, or inhibit
      neutrophil immobilisation induced by externally added Mn(2+). Thus cytoskeletal
      rearrangement was directly implicated in upregulation and, later, downregulation
      of CD11b/CD18 binding. Inhibition of RhoA with C3-transferase caused a dose
      dependent reduction of initial rolling adhesion of neutrophils, and reduced the
      rate of migration after stimulation; however, neither the conversion of rolling
      to stationary adhesion, nor the ability of neutrophils to detach on removal of
      the stimulus, were inhibited. Thus, Rho may regulate actin polymerisation and
      motility in neutrophils, but did not appear to control integrin-mediated adhesion
      itself. Integrin binding may be promoted by disruption of links to the
      cytoskeleton, effected through depolymerisation of actin or cleavage of linking
      protein talin by calpain. Disruption of actin filaments with cytochalasin D did
      not, however, cause integrin-mediated immobilisation of rolling neutrophils.
      Although the calpain inhibitor calpeptin did inhibit the adhesion response to
      fMLP, this was only at doses where actin polymerisation was also ablated. We
      suggest that the cytoskeleton actively regulates binding conformation of
      CD11b/CD18 as well as its mobility in the membrane.

PMID- 10893190
TI  - Trafficking and signaling through the cytoskeleton: a specific mechanism.
AB  - A specific mechanism for the intracellular translocation of nonvesicle-associated
      proteins is proposed. This movement machinery is based on the assumption that the
      cytoskeleton represents an interconnected network of filamentous macromolecules,
      which extends over the entire cytoplasm. Diffusion along the filaments provides
      an efficient way for movement and with this, for signal transduction, between
      various intracellular compartments. We calculate the First Passage Time (FPT),
      the average time it takes a signaling molecule, diffusing along the cytoskeleton,
      to arrive from the cell surface to the nucleus for the first time. We compare our
      results with the FPT of free diffusion and of diffusion in the permeating
      cytoplasm. The latter is hindered by intracellular organelles and the
      cytoskeleton itself. We find that for filament concentrations even below
      physiological values, the FPT along cytoskeletal filaments converges to that for
      free diffusion. When filaments are considered as obstacles, the FPT grows
      steadily with filament concentration. At realistic filament concentrations the
      FPT is insensitive to local modifications in the cytoskeletal network, including
      bundle formation. We conclude that diffusion along cytoskeletal tracks is a
      reliable alternative to other established ways of intracellular trafficking and
      signaling, and therefore provides an additional level of cell function
      regulation.

PMID- 10893191
TI  - Differential distribution and defence involvement of antimicrobial peptides in
      mussel.
AB  - In previous papers, we characterised 3 types of 4-kDa, cysteine-rich, cationic
      antimicrobial peptides: MGDs (for Mytilus galloprovincialis defensins), mytilins
      and myticins, which are abundant in the mussel hemocytes. In the present work, we
      revealed a differential distribution of the cells expressing the different genes.
      In addition, using confocal and electron microscopy, we confirmed that defensins
      and mytilins were partially located in different sub-types of circulating
      hemocytes although the peptides can be located in the same cell, and even in the
      same granule. We also demonstrated that mytilins exert their microbicidal effect
      within the cells through the process of phagosome-mytilin granule fusion leading
      to the co-location of ingested bacteria and mytilins.

PMID- 10893192
TI  - The COOH-terminal nuclear localization sequence of interferon gamma regulates
      STAT1 alpha nuclear translocation at an intracellular site.
AB  - We have recently shown that the nuclear localization of IFN gamma is mediated by
      a polybasic nuclear localization sequence (NLS) in its C terminus. This NLS is
      required for the full expression of biological activity of IFN gamma, both
      extracellularly and intracellularly. We now show that this NLS plays an integral
      intracellular role in the nuclear translocation of the transcription factor STAT1
      alpha activated by IFN gamma. Treatment of IFN gamma with antibodies to the C
      terminal region (95-133) containing the NLS blocked the induction of STAT1 alpha
      nuclear translocation. The antibodies had no effect on nuclear translocation of
      STAT1 alpha in IFN gamma treated cells. A deletion mutant of human IFN gamma, IFN
      gamma (1-123), which is devoid of the C-terminal NLS region was found to be
      biologically inactive, but was still able to bind to the IFN gamma receptor
      complex on cells with a K(d) similar to that of the wild-type protein. Deletion
      of the NLS specifically abolished the ability of IFN gamma(1-123) to initiate the
      nuclear translocation of STAT1 alpha, which is required for the biological
      activities of IFN gamma following binding to the IFN gamma receptor complex.
      Thus, the NLS region appears to contribute minimally to extracellular high
      affinity receptor-ligand binding, yet exerts a strong functional role in STAT1
      alpha nuclear localization. A high-affinity site for the interaction of the C
      terminal NLS domain of IFN gamma with a K(d) approx. 3 x 10(-8) M(-1) has been
      described by previous studies on the intracellular cytoplasmic domain of the IFN
      gamma receptor alpha-chain. To examine the role of the NLS at the intracellular
      level, we microinjected neutralizing antibodies raised against the C-terminal NLS
      domain of IFN gamma into the cytoplasm of cells before treatment of cells with
      IFN gamma. These intracellular antibodies specifically blocked the nuclear
      translocation of STAT1 alpha following the subsequent treatment of these cells
      extracellularly with IFN gamma. These data show that the NLS domain of IFN gamma
      interacts at an intracellular site to regulate STAT1 alpha nuclear import. A C
      terminal peptide of murine IFN gamma, IFN gamma(95-133), that contains the NLS
      motif, induced nuclear translocation of STAT1 alpha when taken up intracellularly
      by a murine macrophage cell line. Deletion of the NLS motif specifically
      abrogated the ability of this intracellular peptide to cause STAT1 alpha nuclear
      translocation. In cells activated with IFN gamma, IFN gamma was found to as part
      of a complex that contained STAT1 alpha and the importin-alpha analog Npi-1,
      which mediates STAT1 alpha nuclear import. The tyrosine phosphorylation of STAT1
      alpha, the formation of the complex IFN gamma/Npi-1/STAT1 alpha complex and the
      subsequent nuclear translocation of STAT1 alpha were all found to be dependent on
      the presence of the IFN gamma NLS. Thus, the NLS of IFN gamma functions
      intracellularly to directly regulate the activation and ultimate nuclear
      translocation STAT1 alpha.

PMID- 10893193
TI  - Formation of glycine receptor clusters and their accumulation at synapses.
AB  - The glycine receptor is highly enriched in microdomains of the postsynaptic
      neuronal surface apposed to glycinergic afferent endings. There is substantial
      evidence suggesting that the selective clustering of glycine receptor at these
      sites is mediated by the cytoplasmic protein gephyrin. To investigate the
      formation of postsynaptic glycine receptor domains, we have examined the surface
      insertion of epitope-tagged receptor alpha subunits in cultured spinal cord
      neurons after gene transfer by polyethylenimine-adenofection. Expression studies
      were also carried out using the non-neuronal cell line COS-7. Immunofluorescence
      microscopy was performed using wild-type isoforms and an alpha mutant subunit
      bearing the gephyrin-binding motif of the beta subunit. In COS-7 cells,
      transfected glycine receptor alpha subunits had a diffuse surface distribution.
      Following cotransfection with gephyrin, only the mutant subunit formed cell
      surface clusters. In contrast, in neurons all subunits were able to form cell
      surface clusters after transfection. These clusters were not colocalized with
      detectable endogenous gephyrin, and the GlyR beta subunit could not be detected
      in transfected cells. Therefore, exogenous receptors were not assembled as
      heteromeric complexes. A quantitative analysis demonstrated that newly
      synthesized glycine receptor progressively populated endogenous gephyrin
      clusters, since association of both proteins increased as a function of time
      after the onset of receptor synthesis. This phenomenon was accelerated when
      glycine receptor contained the gephyrin-binding domain. Together with previous
      results, these data support a two-step model for glycinergic synaptogenesis
      whereby the gephyrin-independent formation of cell surface clusters precedes the
      gephyrin-mediated postsynaptic accumulation of clusters.

PMID- 10893194
TI  - Actin disruption alters the localization of tau in the growth cones of cerebellar
      granule neurons.
AB  - Cultured cerebellar granule neurons initially extend a single axon, followed by
      the extension of a second axon to attain a bipolar morphology. Differentiation
      culminates with the extension of several short dendrites from the cell body. In
      the present study, we determined the location of the dephosphorylated form of the
      microtubule-associated protein tau (dtau) within the growth cones of newly
      forming axons and examined whether this localization was influenced by the actin
      cytoskeleton. Following elongation of the initial axon at 2-3 days in vitro, dtau
      immunoreactivity was present along the entire length of the axon, becoming most
      intense just proximal to the growth cone. Dtau labeling dropped off dramatically
      along the microtubules of the growth cone and was undetectable along the most
      distal tips of these microtubules. As the initial axon continued to elongate at 3
      4 days in vitro, the actin-rich growth cone peripheral domain characteristically
      underwent a dramatic reduction in size. Dtau immunoreactivity extended all the
      way to the most distal tips of the microtubules in the growth cones of these
      cells. Cytochalasin D and latrunculin A mimicked the effects of this
      characteristic reduction in growth cone size with regard to dtau localization in
      the growth cone. Depolymerization of filamentous actin caused the collapse of the
      peripheral domain and allowed dtau to bind all the way to the most distal tips of
      microtubules in the axon. Upon removal of the drugs, the peripheral domain of the
      growth cone rapidly re-formed and dtau was once again excluded from the most
      distal regions of growth cone microtubules. These findings suggest a novel role
      for actin in determining the localization of the microtubule-associated protein
      &tgr; within the growth cones of neurons.

PMID- 10893196
TI  - Life in the alveolus: who's in charge?

PMID- 10893197
TI  - [Ca(2+)](i) oscillations regulate type II cell exocytosis in the pulmonary
      alveolus.
AB  - Pulmonary surfactant, a critical determinant of alveolar stability, is secreted
      by alveolar type II cells by exocytosis of lamellar bodies (LBs). To determine
      exocytosis mechanisms in situ, we imaged single alveolar cells from the isolated
      blood-perfused rat lung. We quantified cytosolic Ca(2+) concentration
      ([Ca(2+)](i)) by the fura 2 method and LB exocytosis as the loss of cell
      fluorescence of LysoTracker Green. We identified alveolar cell type by
      immunofluorescence in situ. A 15-s lung expansion induced synchronous [Ca(2+)](i)
      oscillations in all alveolar cells and LB exocytosis in type II cells. The
      exocytosis rate correlated with the frequency of [Ca(2+)](i) oscillations.
      Fluorescence of the lipidophilic dye FM1-43 indicated multiple exocytosis sites
      per cell. Intracellular Ca(2+) chelation and gap junctional inhibition each
      blocked [Ca(2+)](i) oscillations and exocytosis in type II cells. We demonstrated
      the feasibility of real-time quantifications in alveolar cells in situ. We
      conclude that in lung expansion, type II cell exocytosis is modulated by the
      frequency of intercellularly communicated [Ca(2+)](i) oscillations that are
      likely to be initiated in type I cells. Thus during lung inflation, type I cells
      may act as alveolar mechanotransducers that regulate type II cell secretion.

PMID- 10893198
TI  - Distribution of ion transport mRNAs throughout murine nose and lung.
AB  - Evidence of absorptive or secretory ion transport in different respiratory
      regions of the mouse was sought by assessing the regional distribution of alpha-,
      beta-, and gamma-epithelial sodium channel (ENaC; Na(+) absorptive), cystic
      fibrosis transmembrane conductor regulator (CFTR), and Na(+)-K(+)-2Cl(-)
      cotransporter mRNAs. High levels of ENaC subunit expression were found in nasal
      surface epithelium and gland ducts. CFTR was expressed in both superficial nasal
      respiratory epithelium and glands. These results are consistent with basal
      amiloride-sensitive Na(+) absorption and cAMP-dependent Cl(-) secretion in murine
      nasal epithelia. Expression of all three ENaC subunits increased progressively
      from trachea to terminal bronchioles. Intermediate levels of CFTR and
      cotransporter expression in bronchial epithelium diminished in bronchioles. The
      low abundance of CFTR mRNA throughout murine pulmonary epithelium is consistent
      with functional data that attributes Cl(-) secretion predominantly to an
      alternative Cl(-) channel. alpha-ENaC as the only mRNA found in all regions of
      airway epithelia is consistent with the alpha-subunit as requisite for Na(+)
      absorption, and the increased expression of alpha-, beta-, and gamma-ENaC in
      distal airways suggests a greater absorptive capability in this region.

PMID- 10893199
TI  - Phenotypic characterization of alveolar monocyte recruitment in acute respiratory
      distress syndrome.
AB  - In 49 acute respiratory distress syndrome (ARDS) patients, the phenotype of
      alveolar macrophages (AMs) was analyzed by flow cytometry. Bronchoalveolar lavage
      (BAL) was performed within 24 h after intubation and on days 3-5, 9-12, and 18-21
      of mechanical ventilation. The 27E10(high)/CD11b(high)/CD71(low)/ 25F9(low)/HLA
      DR(low)/RM3/1(low) AM population in the first BAL indicated extensive monocyte
      influx into the alveolar compartment. There was no evidence of increased local AM
      proliferation as assessed by nuclear Ki67 staining. Sequential BAL revealed two
      distinct patient groups. In one, a decrease in 27E10 and CD11b and an increase in
      CD71, 25F9, HLA DR, and RM3/1 suggested a reduction in monocyte influx and
      maturation of recruited cells into AMs, whereas the second group displayed
      sustained monocyte recruitment. In the first BAL from all patients, monocyte
      chemoattractant protein (MCP)-1 was increased, and AMs displayed elevated MCP-1
      gene expression. In sequential BALs, a decrease in MCP-1 coincided with the
      disappearance of monocyte-like AMs, whereas persistent upregulation of MCP-1
      paralleled ongoing monocyte influx. A highly significant correlation between BAL
      fluid MCP-1 concentration, the predominance of monocyte-like AMs, and the
      severity of respiratory failure was noted.

PMID- 10893200
TI  - Interactions between hypoxia and hypercapnic acidosis on calcium signaling in
      carotid body type I cells.
AB  - The effects of hypercapnic acidosis and hypoxia on intracellular Ca(2+)
      concentration ([Ca(2+)](i)) were determined with Indo 1 in enzymatically isolated
      single type I cells from neonatal rat carotid bodies. Type I cells responded to
      graded hypoxic stimuli with graded [Ca(2+)](i) rises. The percentage of cells
      responding was also dependent on the severity of the hypoxic stimulus. Raising
      CO(2) from 5 to 10 or 20% elicited a significant increase in [Ca(2+)](i) in the
      same cells as those that responded to hypoxia. Thus both stimuli can be sensed by
      each individual cell. When combinations of hypoxic and acidic stimuli were given
      simultaneously, the responses were invariably greater than the response to either
      stimulus given alone. Indeed, in most cases, the response to hypercapnia was
      slightly potentiated by hypoxia. These data provide the first evidence that the
      classic synergy between hypoxic and hypercapnic stimuli observed in the intact
      carotid body may, in part, be an inherent property of the type I cell.

PMID- 10893201
TI  - Mechanical strain-induced proliferation and signaling in pulmonary epithelial
      H441 cells.
AB  - Pulmonary epithelial cells are exposed to mechanical strain during physiological
      breathing and mechanical ventilation. Strain regulates pulmonary growth and
      development and is implicated in volutrauma-induced fibrosis. The mechanisms of
      strain-induced effects are not well understood. It was hypothesized that
      mechanical strain induces proliferation of pulmonary epithelial cells and that
      this is mediated by signals initiated within seconds of strain. To test this
      hypothesis, human pulmonary adenocarcinoma H441 cells were strained in vitro.
      Cyclic as well as tonic strain resulted in increased cellular proliferation.
      Western blot analysis of strained cells demonstrated three newly phosphorylated
      tyrosine residues within 30 s of strain. Phosphorylation of mitogen-activated
      protein kinases p42/44 increased, electrophoretic mobility shift assay
      demonstrated activation of transcription factor activating protein-1, and
      immunohistochemistry demonstrated increased phosphorylation of c-jun in response
      to strain. The tyrosine kinase inhibitor genistein blocked the strain-induced
      proliferation. We conclude that strain induces proliferation in pulmonary
      epithelial cells and that tyrosine kinase activity is necessary to signal the
      proliferative response to mechanical strain.

PMID- 10893202
TI  - Relationship between force and regulatory myosin light chain phosphorylation in
      airway smooth muscle.
AB  - We tested the hypothesis that increases in force at a given cytosolic Ca(2+)
      concentration (i.e., Ca(2+) sensitization) produced by muscarinic stimulation of
      canine tracheal smooth muscle (CTSM) are produced in part by mechanisms
      independent of changes in regulatory myosin light chain (rMLC) phosphorylation.
      This was accomplished by comparing the relationship between rMLC phosphorylation
      and force in alpha-toxin-permeabilized CTSM in the absence and presence of
      acetylcholine (ACh). Forces were normalized to the contraction induced by 10
      microM Ca(2+) in each strip, and rMLC phosphorylation is expressed as a
      percentage of total rMLC. ACh (100 microM) plus GTP (1 microM) significantly
      shifted the Ca(2+)-force relationship curve to the left (EC(50): 0.39 +/- 0.06 to
      0.078 +/- 0.006 microM Ca(2+)) and significantly increased the maximum force
      (104.4 +/- 4.8 to 120.2 +/- 2.8%; n = 6 observations). The Ca(2+)-rMLC
      phosphorylation relationship curve was also shifted to the left (EC(50): 1.26 +/-
      0.57 to 0.13 +/- 0.04 microM Ca(2+)) and upward (maximum rMLC phosphorylation:
      70.9 +/- 7.9 to 88.5 +/- 5. 1%; n = 6 observations). The relationships between
      rMLC phosphorylation and force constructed from mean values at corresponding
      Ca(2+) concentrations were not different in the presence and absence of ACh. We
      find no evidence that muscarinic stimulation increases Ca(2+) sensitivity in CTSM
      by mechanisms other than increases in rMLC phosphorylation.

PMID- 10893203
TI  - Effects of neurokinin receptor antagonists in virus-infected airways.
AB  - We investigated the effects of a neurokinin-1 (NK(1)) receptor antagonist (SR
      140333) and a NK(2) receptor antagonist (SR-48968) on airway responsiveness and
      on the function of neuronal M(2) muscarinic receptors, which normally inhibit
      vagal acetylcholine release, in guinea pigs infected with parainfluenza virus.
      Antagonists were given 1 h before infection and daily thereafter. Four days
      later, bronchoconstriction induced by either intravenous histamine (which is
      partly vagally mediated) or electrical stimulation of the vagus nerves was
      increased by viral infection compared with control. In addition, the ability of
      the muscarinic agonist pilocarpine to inhibit vagally induced bronchoconstriction
      was lost in virus-infected animals, demonstrating loss of neuronal M(2) receptor
      function. Macrophage influx into the lungs was inhibited by pretreatment with
      both antagonists. However, only the NK(1) receptor antagonist prevented M(2)
      receptor dysfunction and inhibited hyperresponsiveness (measured as an increase
      in either vagally induced or histamine-induced bronchoconstriction). Thus virus
      induced M(2) receptor dysfunction and hyperresponsiveness are prevented by a
      NK(1) receptor antagonist, but not by a NK(2) receptor antagonist, whereas both
      antagonists had similar anti-inflammatory effects.

PMID- 10893204
TI  - Altered intracellular pH regulation in neutrophils from patients with cystic
      fibrosis.
AB  - Cystic fibrosis (CF) is a condition characterized by neutrophil-mediated lung
      damage and bacterial colonization. The physiological basis for reported
      functional alterations in CF neutrophils, including increased release of
      neutrophil elastase, myeloperoxidase, and oxidants, is unknown. These processes
      are, however, regulated by intracellular pH (pH(i)). We demonstrate here that
      pH(i) regulation is altered in neutrophils from CF patients. Although resting
      pH(i) is similar, pH(i) after acid loading and activation (N-formyl-methionyl
      leucyl-phenylalanine and phorbol 12-myristate 13-acetate) is more acidic in CF
      cells than in normal cells. Furthermore, patients with non-CF-related
      bronchiectasis handle acid loading and activation in a fashion similar to
      subjects with normal neutrophils, suggesting that chronic pulmonary inflammation
      alone does not explain the difference in pH(i). This is further supported by data
      showing that normal neutrophils exposed to the CF pulmonary milieu respond by
      increasing pH(i) as opposed to decreasing pH(i) as seen in activated CF
      neutrophils. These pH(i) differences in activated or acid-loaded CF neutrophils
      are abrogated by ZnCl(2) but not by amiloride and bafilomycin A(1), suggesting
      that passive proton conductance is abnormal in CF. In addition, DIDS, which
      inhibits HCO(3)(-)/Cl(-) exchange, causes alkalinization of control but not of CF
      neutrophils, suggesting that anion transport is also abnormal in CF neutrophils.
      In summary, we have shown that pH(i) regulation in CF neutrophils is
      intrinsically abnormal, potentially contributing to the pulmonary manifestations
      of the condition.

PMID- 10893205
TI  - Platelet-activating factor contributes to acute lung leak in rats given
      interleukin-1 intratracheally.
AB  - Lung lavage fluid of patients with acute lung injury (ALI) has increased levels
      of interleukin-1 (IL-1) and neutrophils, but their relationship to the lung leak
      that characterizes these patients is unclear. To address this concern, we
      investigated the role of the neutrophil agonist platelet-activating factor [1-O
      alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF)] in the development of the acute
      neutrophil-dependent lung leak that is induced by giving IL-1 intratracheally to
      rats. We found that PAF acetyltransferase and PAF activities increased in lungs
      of rats given IL-1 intratracheally compared with lungs of sham-treated rats given
      saline intratracheally. The participation of PAF in the development of lung leak
      and lung neutrophil accumulation after IL-1 administration was suggested when
      treatment with WEB-2086, a commonly used PAF-receptor antagonist, decreased lung
      leak, lung myeloperoxidase activity, and lung lavage fluid neutrophil increases
      in rats given IL-1 intratracheally. Additionally, neutrophils recovered from the
      lung lavage fluid of rats given IL-1 intratracheally reduced more nitro blue
      tetrazolium (NBT) in vitro than neutrophils recovered from control rats or rats
      that had been given WEB-2086 and then IL-1. Histological examination indicated
      that the endothelial cell-neutrophil interfaces of cerium chloride-stained lung
      sections of rats given IL-1 contained increased cerium perhydroxide (the reaction
      product of cerium chloride with hydrogen peroxide) compared with lungs of control
      rats or rats treated with WEB-2086 and then given IL-1 intratracheally. These in
      vivo findings were supported by parallel findings showing that WEB-2086 treatment
      decreased neutrophil adhesion to IL-1-treated cultured endothelial cells in
      vitro. We concluded that PAF contributes to neutrophil recruitment and neutrophil
      activation in lungs of rats given IL-1 intratracheally.

PMID- 10893206
TI  - Retinoic acid stimulates immature lung fibroblast growth via a PDGF-mediated
      autocrine mechanism.
AB  - All trans-retinoic acid (RA) enhances alveolarization in neonates and reinitiates
      alveolarization in emphysematous adult rat lungs, suggesting that RA may
      stimulate cell proliferation by upregulating growth factor ligand and/or receptor
      expression either indirectly or directly by acting on RA-responsive genes
      encoding growth factors. We report that RA and 1,25-dihydroxyvitamin D(3) (Vit
      D), alone and in combination, significantly increase [(3)H]thymidine
      incorporation in cultured fetal and postnatal rat lung fibroblasts (P < 0.05).
      The greatest increase (11-fold) was seen in 4-day cells treated with the two
      agents in combination (P < 0.0001). [(3)H]thymidine incorporation was age
      dependent. The greatest response to RA occurred in 4-day fibroblasts (P < 0.01),
      whereas the response to Vit D was greatest in embryonic day 20 fibroblasts (P <
      0.001). Neutralizing antibody to platelet-derived growth factor (PDGF)-AB
      decreased [(3)H]thymidine incorporation in response to RA alone or in combination
      with Vit D, indicating a role for PDGF. Expression of mRNAs for PDGF-A and PDGF
      receptor (PDGFR)-alpha and -beta was upregulated at the transcriptional level in
      an age- and treatment-dependent manner. Thus exogenous RA may influence
      alveolarization by stimulating fibroblast proliferation through a PDGF-mediated
      autocrine mechanism, which is enhanced when RA and Vit D are administered in
      combination.

PMID- 10893207
TI  - Different pathways of degradation of SP-A and saturated phosphatidylcholine by
      alveolar macrophages.
AB  - Alveolar macrophages degrade surfactant protein (SP) A and saturated
      phosphatidycholine [dipalmitoylphosphatidylcholine (DPPC)]. To clarify this
      process, using rabbit alveolar macrophages, we analyzed the effect of drugs known
      to affect phagocytosis, pinocytosis, clathrin-mediated uptake, caveolae, the
      cytoskeleton, lysosomal pH, protein kinase C, and phosphatidylinositol 3-kinase
      (PI3K) on the degradation of SP-A and DPPC. We found the following: 1) SP-A binds
      to the plasma membrane, is rapidly internalized, and then moves toward
      degradative compartments. Uptake could be clathrin mediated, whereas
      phagocytosis, pinocytosis, or the use of caveolae are less likely. An intact
      cytoskeleton and an acidic milieu are necessary for the degradation of SP-A. 2)
      Stimulation of protein kinase C increases the degradation of SP-A. 3) PI3K
      influences the degradation of SP-A by regulating both the speed of
      internalization and subsequent intracellular steps, but its inhibition does not
      prevent SP-A from reaching the lysosomal compartment. 4) The degradation of DPPC
      is unaffected by most of the treatments able to influence the degradation of SP
      A. Thus it appears that DPPC is degraded by alveolar macrophages through
      mechanisms very different from those utilized for the degradation of SP-A.

PMID- 10893208
TI  - E. coli hemolysin-induced lipid mediator metabolism in alveolar macrophages:
      impact of eicosapentaenoic acid.
AB  - Escherichia coli hemolysin (HlyA) is a prototype of a large family of pore
      forming proteinaceous exotoxins that have been implicated in the pathogenetic
      sequelae of severe infection and sepsis, including development of acute lung
      injury. In the present study in rabbit alveolar macrophages (AMs), subcytolytic
      concentrations of purified HlyA evoked rapid synthesis of platelet-activating
      factor, with quantities approaching those in response to maximum calcium
      ionophore challenge. In parallel, large quantities of leukotriene (LT) B(4) and 5
      , 8-, 9-, 12-, and 15-hydroxyeicosatetraenoic acid (HETE) were liberated from
      HlyA-exposed AMs depending on exogenous arachidonic acid (AA) supply.
      Coadministration of eicosapentaenoic acid (EPA) dose dependently suppressed
      generation of the proinflammatory lipoxygenase products LTB(4) and 5-, 8-, 9-,
      and 12-HETE in parallel with the appearance of the corresponding EPA-derived
      metabolites LTB(5) and 5-, 8-, 9-, and 12-hydroxyeicosapentaenoic acid (HEPE). At
      equimolar concentrations, EPA turned out to be the preferred substrate over AA
      for these AM lipoxygenase pathways, with the sum of LTB(5) and 5-, 8-, 9-, and 12
      HEPE surpassing the sum of LTB(4) and 5-, 8-, 9-, and 12-HETE by >80-fold. In
      contrast, coadminstration of EPA did not significantly reduce HlyA-elicited
      generation of the anti-inflammatory AA lipoxygenase product 15-HETE. We conclude
      that AMs are sensitive target cells for HlyA attack, resulting in marked
      proinflammatory lipid mediator synthesis. In the presence of EPA, lipoxygenase
      product formation is shifted from a pro- to an anti-inflammatory profile.

PMID- 10893209
TI  - Comparison of SP-A and LPS effects on the THP-1 monocytic cell line.
AB  - Surfactant protein A (SP-A) increases production of proinflammatory cytokines by
      monocytic cells, including THP-1 cells, as does lipopolysaccharide (LPS). Herein
      we report differences in responses to these agents. First, polymyxin B inhibits
      the LPS response but not the SP-A response. Second, SP-A-induced increases in
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-8
      are reduced by >60% if SP-A is preincubated with Survanta (200 microgram/ml) for
      15 min before addition to THP-1 cells. However, the LPS effects on TNF-alpha and
      IL-8 are inhibited by <20% and the effect on IL-1beta by <50%. Third, at Survanta
      levels of 1 mg/ml, SP-A-induced responses are reduced by >90%, and although the
      inhibitory effects on LPS action increase, they still do not reach those seen
      with SP-A. Finally, we tested whether SP-A could induce tolerance as LPS does.
      Pretreatment of THP-1 cells with LPS inhibits their response to subsequent LPS
      treatment 24 h later, including TNF-alpha, IL-1beta, and IL-8. Similar treatment
      with SP-A reduces TNF-alpha, but IL-1beta and IL-8 are further increased by the
      second treatment with SP-A rather than inhibited as with LPS. Thus, whereas both
      SP-A and LPS stimulate cytokine production, their mechanisms differ with respect
      to inhibition by surfactant lipids and in ability to induce tolerance.

PMID- 10893210
TI  - Incorporation of biotinylated SP-A into rat lung surfactant layer, type II cells,
      and clara cells.
AB  - The goal of this study was to compare the functions of Clara and type II cells
      during alveolar clearance and recycling of surfactant protein (SP) A, a secretory
      product of both cell types. We examined the incorporation of instilled
      biotinylated SP-A (bSP-A) into rat lung type II and Clara cells as a measure of
      clearance and recycling of the protein. Ultrastructural localization of bSP-A was
      accomplished by an electron-microscopic immunogold technique at 7, 30, and 120
      min after intratracheal instillation. Localization of bSP-A was quantitatively
      evaluated within extracellular surfactant components (lipid-rich forms: myelin
      figures, vesicles, and tubular myelin; and lipid-poor hypophase) and in
      compartments of type II and Clara cells. bSP-A was incorporated into myelinic and
      vesicular forms of extracellular surfactant, but tubular myelin and hypophase had
      little bSP-A. Lamellar bodies of type II cells demonstrated a significant time
      dependent increase in their incorporation of bSP-A. There was a concentration of
      bSP-A in the secretory granules and mitochondria of Clara cells, but no Clara
      cell compartment showed a pattern of time-dependent change in immunolabeling. Our
      immunolabeling data demonstrated a time-dependent movement of exogenous SP-A from
      extracellular components into type II cells and their secretory granules. Clara
      cells did not demonstrate a time-dependent incorporation of bSP-A into their
      secretory granules during the period of this study. If Clara cells recycle SP-A,
      they must reach a steady state very quickly or very slowly.

PMID- 10893211
TI  - Ethanol ingestion via glutathione depletion impairs alveolar epithelial barrier
      function in rats.
AB  - We determined that rats fed a liquid diet containing ethanol (36% of calories)
      for 6 wk had decreased (P < 0.05) net vectorial fluid transport and increased (P
      < 0.05) bidirectional protein permeability across the alveolar epithelium in vivo
      compared with rats fed a control diet. However, both groups increased (P < 0.05)
      fluid transport in response to epinephrine (10(-5) M) stimulation, indicating
      that transcellular sodium transport was intact. In parallel, type II cells
      isolated from ethanol-fed rats and cultured for 8 days formed a more permeable
      monolayer as reflected by increased (P < 0.05) leak of [(14)C]inulin. However,
      type II cells from ethanol-fed rats had more sodium-permeant channels in their
      apical membranes than type II cells isolated from control-fed rats, consistent
      with the preserved response to epinephrine in vivo. Finally, the alveolar
      epithelium of ethanol-fed rats supplemented with L-2-oxothiaxolidine-4
      carboxylate (Procysteine), a glutathione precursor, had the same (P < 0.05) net
      vectorial fluid transport and bidirectional protein permeability in vivo and
      permeability to [(14)C]inulin in vitro as control-fed rats. We conclude that
      chronic ethanol ingestion via glutathione deficiency increases alveolar
      epithelial intercellular permeability and, despite preserved or even enhanced
      transcellular sodium transport, renders the alveolar epithelium susceptible to
      acute edematous injury.

PMID- 10893212
TI  - Regenerative growth of respiratory bronchioles in dogs.
AB  - Loss of lung units due to pneumonectomy stimulates growth of the remaining lung.
      It is generally believed that regenerative lung growth involves only alveoli but
      not airways, a dissociated response termed "dysanaptic growth." We examined the
      structural response of respiratory bronchioles in immature dogs raised to
      maturity after right pneumonectomy. In another group of adult dogs, we also
      examined the effect of preventing mediastinal shift after right pneumonectomy on
      the response of respiratory bronchioles. In immature dogs after pneumonectomy,
      the volume of the remaining lung increased twofold, with no change in volume
      density, numerical density, or mean diameter of respiratory bronchiole, compared
      with that in the control lung. The number of respiratory bronchiole segments and
      branch points increased proportionally with lung volume. In adult dogs after
      pneumonectomy, prevention of mediastinal shift reduced lung strain at a given
      airway pressure, but lung expansion and regenerative growth of respiratory
      bronchiole were not eliminated. We conclude that postpneumonectomy lung growth is
      associated with proliferation of intra-acinar airways. The proportional growth of
      acinar airways and alveoli should optimize gas exchange of the regenerated lung
      by enhancing gas conductance and mixing efficiency within the acinus.

PMID- 10893213
TI  - Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by
      captopril or by a caspase inhibitor.
AB  - Angiotensin-converting enzyme is involved in apoptosis of alveolar epithelial
      cells (Wang R, Zagariya A, Ang E, Ibarra-Sunga O, and Uhal BD. Am J Physiol Lung
      Cell Mol Physiol 277: L1245-L1250, 1999). This study tested the ability of the
      angiotensin-converting enzyme inhibitor captopril or the caspase inhibitor Z-Val
      Ala-Asp-fluoromethylketone (ZVAD-fmk) to block alveolar epithelial cell apoptosis
      and lung fibrosis in vivo in response to bleomycin (Bleo). Male Wistar rats
      received 8 U/kg of Bleo (bleomycin sulfate) or vehicle intratracheally. Subgroups
      of Bleo-treated rats received captopril, ZVAD-fmk, or vehicle alone. Lung
      collagen was assessed by picrosirius red or hydroxyproline assay at 1, 7, and 14
      days post-Bleo, and apoptosis was detected by in situ end labeling (ISEL). Bleo
      increased alveolar septal and peribronchial collagen by 100 and 133%,
      respectively (both P < 0.01), by day 14 but not earlier. In contrast, ISEL was
      increased in alveolar and airway cells at all time points. Captopril or ZVAD-fmk
      inhibited collagen accumulation by 91 and 85%, respectively (P < 0. 01). Both
      agents also inhibited ISEL in alveoli by 99 and 81% and in airways by 67 and 63%,
      respectively. These data suggest that the efficacy of captopril to inhibit
      experimental lung fibrogenesis is related to inhibition of apoptosis. They also
      demonstrate the antifibrotic potential of a caspase inhibitor.

PMID- 10893214
TI  - Induction of pulmonary matrilysin expression by combustion and ambient air
      particles.
AB  - The molecular mechanism(s) by which chemically complex air pollution particles
      mediate their adverse health effects is not known. We have examined the ability
      of combustion and ambient air particles to induce pulmonary matrilysin expression
      due to the well-documented role of matrix metalloproteinases in tissue injury and
      repair responses. Rats were exposed to saline, residual oil fly ash (2.5 mg/rat),
      or ambient air particles (2.5 mg/rat) via intratracheal instillation and examined
      3-72 h after exposure. Saline-exposed animals had low levels of matrilysin mRNA,
      whereas the animals exposed to either complex particle showed an early induction
      of pulmonary matrilysin gene expression as well as of the 19-kDa activated form
      of matrilysin. Immunocytochemistry and in situ hybridization analyses identified
      the alveolar macrophages and monocytes as primary sources of air pollution
      particle-induced matrilysin expression. Matrilysin gene induction and protein
      activation by combustion and ambient air particles correlated with the early
      histopathological changes produced by these particles. These results demonstrate
      the ability of combustion and ambient air particles to induce pulmonary
      matrilysin expression and suggest a role for this matrix metalloproteinase in the
      initiation of lung injury produced by these particles.

PMID- 10893215
TI  - Transglutaminase-mediated fibronectin multimerization in lung endothelial matrix
      in response to TNF-alpha.
AB  - Exposure of lung endothelial monolayers to tumor necrosis factor (TNF)-alpha
      causes a rearrangement of the fibrillar fibronectin (FN) extracellular matrix and
      an increase in protein permeability. Using calf pulmonary artery endothelial cell
      layers, we determined whether these changes were mediated by FN multimerization
      due to enhanced transglutaminase activity after TNF-alpha (200 U/ml) for 18 h.
      Western blot analysis indicated that TNF-alpha decreased the amount of monomeric
      FN detected under reducing conditions. Analysis of (125)I-FN incorporation into
      the extracellular matrix confirmed a twofold increase in high molecular mass
      (HMW) FN multimers stable under reducing conditions (P < 0.05). Enhanced
      formation of such HMW FN multimers was associated with increased cell surface
      transglutaminase activity (P < 0.05). Calf pulmonary artery endothelial cells
      pretreated with TNF-alpha also formed nonreducible HMW multimers of FN when
      layered on surfaces precoated with FN. Inhibitors of transglutaminase blocked the
      TNF-alpha-induced formation of nonreducible HMW multimers of FN but did not
      prevent either disruption of the FN matrix or the increase in monolayer
      permeability. Thus increased cell surface transglutaminase after TNF-alpha
      exposure initiates the enhanced formation of nonreducible HMW FN multimers but
      did not cause either the disruption of the FN matrix or the increase in
      endothelial monolayer permeability.

PMID- 10893216
TI  - AP-1 and STAT mediate hyperoxia-induced gene transcription of heme oxygenase-1.
AB  - We have previously shown marked induction of the stress-inducible gene heme
      oxygenase-1 (HO-1) in vivo and in vitro after hyperoxia. In RAW 264.7 cells, HO-1
      induction is transcriptionally regulated and dependent on cooperation between the
      HO-1 gene promoter and the 5' distal enhancer element SX2. In our present study,
      further deletional and mutational analyses demonstrate that signal transducer and
      activator of transcription (STAT) DNA binding sites located in the promoter of HO
      1 and activator protein (AP)-1 DNA binding sites in the distal enhancer element
      SX2 are necessary for optimal HO-1 gene activation after hyperoxia.
      Interestingly, a second 5' distal enhancer element, AB1, located 10 kb upstream
      from the HO-1 promoter, alone is activated after hyperoxia but cannot confer
      maximal hyperoxia-induced HO-1 gene transcription. Mutational analysis of the AB1
      enhancer shows that AP-1 is essential for AB1-mediated HO-1 gene transcription
      after hyperoxia. Electromobility shift assays show increased STAT1, STAT3, STAT5,
      and AP-1 DNA binding activity in RAW 264.7 cells after hyperoxia. Taken together,
      our data suggest that the 5' distal enhancer elements of the HO-1 gene in concert
      with the promoter regulate HO-1 gene induction and highlight the complexity of HO
      1 gene transcription in response to hyperoxia.

PMID- 10893218
TI  - Parathyroid hormone-related protein reduces alveolar epithelial cell
      proliferation during lung injury in rats.
AB  - Parathyroid hormone-related protein (PTHrP) is a growth inhibitor for alveolar
      type II cells and could be a regulatory factor for alveolar epithelial cell
      proliferation after lung injury. We investigated lung PTHrP expression in rats
      exposed to 85% oxygen. Lung levels of PTHrP were significantly decreased between
      4 and 8 days of hyperoxia, concurrent with increased expression of proliferating
      cell nuclear antigen and increased incorporation of 5-bromo-2'-deoxyuridine
      (BrdU) into DNA in lung corner cells. PTHrP receptor was present in both normal
      and hyperoxic lung. To test whether the fall in PTHrP was related to cell
      proliferation, we instilled PTHrP into lungs on the fourth day of hyperoxia.
      Eight hours later, BrdU labeling in alveolar corner cells was 3.2 +/- 0.4
      cells/high-power field in hyperoxic PBS-instilled rats compared with 0.5 +/- 0.3
      cells/high-power field in PTHrP-instilled rats (P < 0. 01). Thus PTHrP expression
      changes in response to lung injury due to 85% oxygen and may regulate cell
      proliferation.

PMID- 10893217
TI  - Integrin alpha(3)-subunit expression modulates alveolar epithelial cell monolayer
      formation.
AB  - We investigated expression of the alpha(3)-integrin subunit by rat alveolar
      epithelial cells (AECs) grown in primary culture as well as the effects of
      monoclonal antibodies with blocking activity against the alpha(3)-integrin
      subunit on AEC monolayer formation. alpha(3)-Integrin subunit mRNA and protein
      were detectable in AECs on day 1 and increased with time in culture. alpha(3)-
      and beta(1)-integrin subunits coprecipitated in immunoprecipitation experiments
      with alpha(3)- and beta(1)-subunit-specific antibodies, consistent with their
      association as the alpha(3)beta(1)-integrin receptor at the cell membrane.
      Treatment with blocking anti-alpha(3) monoclonal antibody from day 0 delayed
      development of transepithelial resistance, reduced transepithelial resistance
      through day 5 compared with that in untreated AECs, and resulted in large
      subconfluent patches in monolayers viewed by scanning electron microscopy on day
      3. These data indicate that alpha(3)- and beta(1)-integrin subunits are expressed
      in AEC monolayers where they form the heterodimeric alpha(3)beta(1)-integrin
      receptor at the cell membrane. Blockade of the alpha(3)-integrin subunit inhibits
      formation of confluent AEC monolayers. We conclude that the alpha(3)-integrin
      subunit modulates formation of AEC monolayers by virtue of the key role of the
      alpha(3)beta(1)-integrin receptor in AEC adhesion.

PMID- 10893219
TI  - TGF-beta1 stimulates IL-8 release, COX-2 expression, and PGE(2) release in human
      airway smooth muscle cells.
AB  - We have recently shown that endogenous prostanoids are critical in bradykinin
      stimulated interleukin (IL)-8 release from human airway smooth muscle (ASM)
      cells. In this study, we tested the ability of transforming growth factor (TGF)
      beta1 to stimulate IL-8 release, cyclooxygenase (COX)-2 expression and PGE(2)
      generation in cultured human ASM cells and explored the role of COX products and
      COX-2 induction on IL-8 release. TGF-beta1 stimulated IL-8 release, COX-2
      induction, and PGE(2) generation in a concentration- and time-dependent manner.
      Maximal IL-8 release was achieved with 10 ng/ml of TGF-beta1 after 16 h of
      incubation, which was inhibited by the transcription inhibitor actinomycin D and
      the corticosteroid dexamethasone but was not affected by the nonselective COX
      inhibitor indomethacin and the selective COX-2 inhibitor NS-398 despite their
      inhibition on TGF-beta1-induced PGE(2) release. These results show for the first
      time that TGF-beta1 stimulates IL-8 release, COX-2 induction, and PGE(2)
      generation in human ASM cells and that PGE(2) generation is not critical for TGF
      beta1-induced IL-8 release. These findings suggest that TGF-beta1 may play an
      important role in the pathophysiology of asthma.

PMID- 10893220
TI  - Steric hindrance regulation of the Pseudomonas aeruginosa amidase operon.
AB  - Expression of the amidase operon of Pseudomonas aeruginosa is controlled by AmiC,
      the ligand sensor and negative regulator, and AmiR the transcription
      antitermination factor activator. We have titrated out AmiC repression activity
      in vivo by increased AmiR production in trans and shown AmiC regulation of the
      antitermination activity of AmiR by a steric hindrance mechanism. In the presence
      of the co-repressor butyramide we have isolated a stable AmiC.AmiR complex.
      Addition of the inducing ligand acetamide to the complex trips the molecular
      switch, causing complex dissociation and release of AmiR. The AmiC.AmiR
      butyramide complex exhibits acetamide-dependent, sequence-specific RNA binding
      activity and a K(d) of 1.0 nm has been calculated for the AmiR.RNA interaction.
      The results show that amidase operon expression is controlled by a novel type of
      signal transduction system in which activity of a site-specific RNA binding
      activator is regulated via a sequestration mechanism.

PMID- 10893221
TI  - RhoA and rho kinase regulate the epithelial Na+/H+ exchanger NHE3. Role of myosin
      light chain phosphorylation.
AB  - The activity of the Na(+)/H(+) exchanger NHE3 isoform, which is found primarily
      in epithelial cells, is sensitive to the state of actin polymerization. Actin
      assembly, in turn, is controlled by members of the small GTPase Rho family,
      namely Rac1, Cdc42, and RhoA. We therefore investigated the possible role of
      these GTPases in modulating NHE3 activity. Cells stably expressing NHE3 were
      transiently transfected with inhibitory forms of Rac1, Cdc42, or RhoA and
      transport activity was assessed using microfluorimetry. NHE3 activity was not
      adversely affected by either dominant-negative Rac1 or Cdc42. By contrast, the
      inhibitory form of RhoA greatly depressed NHE3 activity, without noticeably
      altering its subcellular distribution. NHE3 activity was equally reduced by
      inhibiting p160 Rho-associated kinase I (ROK), a downstream effector of RhoA,
      with the selective antagonist Y-27632 and a dominant-negative form of ROK.
      Furthermore, inhibition of ROK reduced the phosphorylation of myosin light chain.
      A comparable net dephosphorylation was achieved by the myosin light chain kinase
      inhibitor ML9, which similarly inhibited NHE3. These data suggest that optimal
      NHE3 activity requires a functional RhoA-ROK signaling pathway which acts, at
      least partly, by controlling the phosphorylation of myosin light chain and,
      ultimately, the organization of the actin cytoskeleton.

PMID- 10893222
TI  - Light intermediate chain 1 defines a functional subfraction of cytoplasmic dynein
      which binds to pericentrin.
AB  - The light intermediate chains (LICs) of cytoplasmic dynein consist of multiple
      isoforms, which undergo post-translational modification to produce a large number
      of species separable by two-dimensional electrophoresis and which we have
      proposed to represent at least two gene products. Recently, we demonstrated the
      first known function for the LICs: binding to the centrosomal protein,
      pericentrin, which represents a novel, non-dynactin-based cargo-binding
      mechanism. Here we report the cloning of rat LIC1, which is approximately 75%
      homologous to rat LIC2 and also contains a P-loop consensus sequence. We compared
      LIC1 and LIC2 for the ability to interact with pericentrin, and found that only
      LIC1 will bind. A functional P-loop sequence is not required for this
      interaction. We have mapped the interaction to the central region of both LIC1
      and pericentrin. Using recombinant LICs, we found that they form homooligomers,
      but not heterooligomers, and exhibit mutually exclusive binding to the heavy
      chain. Additionally, overexpressed pericentrin is seen to interact with
      endogenous LIC1 exclusively. Together these results demonstrate the existence of
      two subclasses of cytoplasmic dynein: LIC1-containing dynein, and LIC2-containing
      dynein, only the former of which is involved in pericentrin association with
      dynein.

PMID- 10893223
TI  - Distinct but overlapping sites within the cytoplasmic dynein heavy chain for
      dimerization and for intermediate chain and light intermediate chain binding.
AB  - Cytoplasmic dynein is a molecular motor complex consisting of four major classes
      of polypeptide: the catalytic heavy chains (HC), intermediate chains (IC), light
      intermediate chains (LIC), and light chains (LC). Previous studies have reported
      that the ICs bind near the N terminus of the HCs, which is thought to correspond
      to the base of the dynein complex. In this study, we co-overexpressed cytoplasmic
      dynein subunits in COS-7 cells to map HC binding sites for the ICs and LICs, as
      well as HC dimerization. We have found that the LICs bind directly to the N
      terminus of the HC, adjacent to and overlapping with the IC binding site,
      consistent with a role for the LICs in cargo binding. Mutation of the LIC P-loop
      had no detectable effect on HC binding. We detected no direct interaction between
      the ICs and LICs. Using triple overexpression of HC, IC and LIC, we found that
      both IC and LIC are present in the same complexes, a result verified by anti-IC
      immunoprecipitation of endogenous complexes and immunoblotting. Our results
      indicate that the LICs and ICs must be located on independent surfaces of
      cytoplasmic dynein to allow each to interact with other proteins without steric
      interference.

PMID- 10893225
TI  - Identification of an intermediate state in the helix-coil degradation of collagen
      by ultraviolet light.
AB  - Differential scanning calorimetry has revealed the presence of a new denaturation
      endotherm at 32 degrees C following UV irradiation of collagen, compared with 39
      degrees C for the native triple helix. Kinetic analyses showed that the new peak
      was a previously unknown intermediate state in the collagen helix-coil transition
      induced by UV light, and at least 80% of the total collagen was transformed to
      random chains via this state. Its rate of formation was increased by hydrogen
      peroxide and inhibited by free radical scavengers. SDS-polyacrylamide gels showed
      evidence of competing reactions of cross-linking and random primary chain
      scission. The cross-linking was evident from initial gelling of the collagen
      solution, but there was no evidence for a dityrosine cross-link. Primary chain
      scission was confirmed by end group analysis using fluorescamine. Electron
      microscopy showed that the segment long spacing crystallites formed from the
      intermediate state were identical to the native molecules. Clearly, collagen can
      undergo quite extensive damage by cleavage of peptide bonds without disorganizing
      the triple helical structure. This leads to the formation of a damaged
      intermediate state prior to degradation of the molecules to short random chains.

PMID- 10893224
TI  - Molecular cloning and expression of the Fabs of human autoantibodies in
      Escherichia coli. Determination of the heavy or light chain contribution to the
      anti-DNA/-cardiolipin activity of the Fab.
AB  - The Fabs of three human autoantibodies (B3/33H11, anti-DNA; UK4, anti
      phospholipid) and six related hybrids have been cloned, expressed in Escherichia
      coli, and purified to homogeneity. SDS-polyacrylamide gel electrophoresis and
      Western blot analysis of the recombinant Fab demonstrated the purified Fab to be
      of correct size and in assembled form. Protein expression levels of up to 5-9 mg
      per liter of culture were achievable. A sensitive and reliable comparative anti
      DNA enzyme-linked immunosorbent assay, involving a defined biotinylated 35-mer
      oligonucleotide in its single- or double-stranded form, is also described.
      Crithidia assay and anti-DNA or anti-cardiolipin antibody enzyme-linked
      immunosorbent assay analyses demonstrated convincing binding of the recombinant
      Fab proteins to DNA/cardiolipin, confirming the expression of functional
      molecule. The comparative DNA/cardiolipin binding analyses of the nine Fabs
      revealed that the anti-DNA (light, B3/33H11) or anti-cardiolipin (heavy, UK4)
      activity lies predominantly on one of the two chains. However, a compatible
      partner chain is necessary for optimum antigen binding activity of the antibody.

PMID- 10893226
TI  - Deltorphin II-induced rapid desensitization of delta-opioid receptor requires
      both phosphorylation and internalization of the receptor.
AB  - Similar to other G protein-coupled receptors, rapid phosphorylation of the delta
      opioid receptor in the presence of agonist has been reported. Hence, agonist
      induced desensitization of the delta-opioid receptor has been suggested to be via
      the receptor phosphorylation, arrestin-mediated pathway. However, due to the
      highly efficient coupling between the delta-opioid receptor and the adenylyl
      cyclase, the direct correlation between the rates of receptor phosphorylation and
      receptor desensitization as measured by the adenylyl cyclase activity could not
      be established. In the current studies, using an ecdysone-inducible expression
      system to control the delta-opioid receptor levels in HEK293 cells, we could
      demonstrate that the rate of deltorphin II-induced receptor desensitization is
      dependent on the receptor level. Only at receptor concentrations </=90 fmol/mg of
      protein were rapid desensitizations (t(12) <10 min) observed. Apparently,
      deltorphin II-induced receptor desensitization involves cellular events in
      addition to receptor phosphorylation. Mutation of Ser(363) in the carboxyl tail
      of the delta-opioid receptor to Ala completely abolished the deltorphin II
      induced receptor phosphorylation but not the desensitization response. Although
      the magnitude of desensitization was attenuated, the rate of deltorphin II
      induced receptor desensitization remained the same in the S363A mutant as
      compared with wild type. Also, the S363A mutant could internalize in the presence
      of deltorphin II. Only when the agonist-induced clathrin-coated pit-mediated
      receptor internalization was blocked by 0.4 m sucrose that the deltorphin II
      induced receptor desensitization was abolished in the S363A mutant. Similarly,
      0.4 m sucrose could partially block the agonist-induced rapid desensitization in
      HEK293 cells expressing the wild type delta-opioid receptor. Taken together,
      these data supported the hypothesis that rapid desensitization of the delta
      opioid receptor involves both the phosphorylation and the internalization of the
      receptor.

PMID- 10893227
TI  - The low pH in trans-Golgi triggers autocatalytic cleavage of pre-alpha -inhibitor
      heavy chain precursor.
AB  - Pre-alpha-inhibitor is a plasma protein whose physiological function is still
      unknown, but in vitro studies suggest that it might be involved in inflammatory
      reactions. Pre-alpha-inhibitor consists of a 25- and a 75-kDa polypeptide:
      bikunin and heavy chain 3 (H3), respectively. H3 is synthesized with a 30-kDa C
      terminal extension, which is released in the Golgi complex through cleavage
      between an Asp and a Pro residue. We now provide evidence that this cleavage is
      triggered by the low pH in the late Golgi and occurs through an intramolecular
      process. First, incubation in vitro of the H3 precursor (proH3) at pH 6.0 or
      lower results in rapid cleavage of the protein. Second, the rate of the cleavage
      reaction does not depend on the concentration of proH3 and is not affected by the
      presence of various protease inhibitors. Third, raising the pH in organelles of
      cells producing proH3 abolishes cleavage during secretion. The amino acid
      residues near the cleavage site of proH3 differ from those of previously
      described self-cleaving proteins, indicating that the mechanisms of scission are
      different.

PMID- 10893228
TI  - Membrane integration of the second transmembrane segment of band 3 requires a
      closely apposed preceding signal-anchor sequence.
AB  - We have investigated the topogenic rules of multispanning membrane proteins using
      erythrocyte band 3. Here, the fine structural requirements for the correct
      disposition of its second transmembrane segment (TM2) were assessed. We made
      fusion proteins where TM1 and the loop sequence preceding TM2 were changed and
      fused to prolactin. They were expressed in a cell-free system supplemented with
      rough microsomal membrane, and their topologies on the membrane were assessed by
      protease sensitivity and N-glycosylation. TM1 was demonstrated to be a signal
      anchor sequence that mediates translocation of the downstream portion, and thus
      TM2 should be responsible to halt the translocation to acquire TM topology. When
      the loop between TM1 and TM2 was elongated, however, TM2 was readily translocated
      through the membrane and not integrated. For the membrane integration of TM2, TM2
      must be in close proximity to TM1. The TM1 can be replaced with another signal
      anchor sequence with a long hydrophobic segment but not with a signal sequence
      with shorter hydrophobic stretch. The length of the hydrophobic segment affected
      final topology of TM2. We concluded that the two TM segments work synergistically
      within the translocon to acquire the correct topology and that the length of the
      preceding signal sequence is critical for stable transmembrane assembly of TM2.
      We propose that direct interaction among the TM segments is one of the critical
      factors for the transmembrane topogenesis of multispanning membrane proteins.

PMID- 10893229
TI  - Multiple regulatory domains control IRF-7 activity in response to virus
      infection.
AB  - Recent studies implicate the interferon regulatory factors (IRF), IRF-3 and IRF
      7, as key activators of Type 1 interferon genes, as well as the RANTES (regulated
      on activation normal T cell expressed) chemokine gene. Both IRF-3 and IRF-7 are
      regulated in part by virus-induced C-terminal phosphorylation, leading to nuclear
      translocation, stimulation of DNA binding, and transcriptional activities.
      Structure-function studies with IRF-7 suggested a complex organization of the C
      terminal region, with a constitutive activation domain located between amino
      acids 150-246, an accessory inducibility region at the very end of IRF-7 between
      amino acids 467 and 503, and an inhibitory region (amino acids 341-467) adjacent
      to the C-terminal end that interferes with transactivation. Furthermore, an
      element that increases basal and virus-inducible activity is located between
      amino acids 278 and 305. A transcriptionally active form of IRF-7 was also
      generated by substitution of Ser-477 and Ser-479 residues with the phosphomimetic
      Asp. IRF-7, particularly IRF-7(S477D/S479D), was a strong transactivator of type
      I interferon and RANTES chemokine gene expression. Unlike wild type IRF-3, IRF-7
      overexpression was able to stimulate inteferon gene expression in the absence of
      virus infection. Using tagged versions of IRF-7 and IRF-3, the formation of homo-
      and heterodimers was detected by co-immunoprecipitation. These results
      demonstrate that IRF-3 and IRF-7 transcription factors possess distinct
      structural characteristics that impart complementary rather than redundant
      functional roles in cytokine gene activation.

PMID- 10893230
TI  - Evidence for major structural changes in the Manduca sexta midgut V1 ATPase due
      to redox modulation. A small angle X-ray scattering study.
AB  - The shape and overall dimensions of the oxidized and reduced form of the V(1)
      ATPase from Manduca sexta were investigated by synchrotron radiation x-ray
      solution scattering. The radius of gyration of the oxidized and reduced complex
      differ noticeably, with dimensions of 6. 20 +/- 0.06 and 5.84 +/- 0.06 nm,
      respectively, whereas the maximum dimensions remain constant at 22.0 +/- 0.1 nm.
      Comparison of the low resolution shapes of both forms, determined ab initio,
      indicates that the main structural alteration occurs in the head piece, where the
      major subunits A and B are located, and at the bottom of the stalk. In
      conjunction with the solution scattering data, decreased susceptibility to
      tryptic digestion and tryptophan fluorescence of the reduced V(1) molecule
      provide the first strong evidence for major structural changes in the V(1) ATPase
      because of redox modulation.

PMID- 10893231
TI  - A family of human RNA-binding proteins related to the Drosophila Bruno
      translational regulator.
AB  - The post-transcriptional regulation of gene expression by RNA-binding proteins is
      an important element in controlling both normal cell functions and animal
      development. The diverse roles are demonstrated by the Elav family of RNA-binding
      proteins, where various members have been shown to regulate several processes
      involving mRNA. We have identified another family of RNA-binding proteins
      distantly related to the Elav family but closely related to Bruno, a
      translational regulator in Drosophila melanogaster. In humans, six Bruno-like
      genes have been identified, whereas other species such as Drosophila, Xenopus
      laevis, and Caenorhabditis elegans have at least two members of this family, and
      related genes have also been detected in plants and ascidians. The human BRUNOL2
      and BRUNOL3 are 92% identical in the RNA-binding domains, although the BRUNOL2
      gene is expressed ubiquitously whereas BRUNOL3 is expressed predominantly in the
      heart, muscle, and nervous system. Both of these proteins bind the same target
      RNA, the Bruno response element. The RNA-binding domain that recognizes the Bruno
      response element is composed of two consecutive RNA recognition motifs at the
      amino terminus of vertebrate Bruno protein. The possible involvement of the Bruno
      family of proteins in the CUG repeat expansion disease myotonic dystrophy is
      discussed.

PMID- 10893232
TI  - High and low affinity heparin-binding sites in the G domain of the mouse laminin
      alpha 4 chain.
AB  - G domains of the mouse laminin alpha 1 and alpha 4 chains consisting of its five
      subdomains LG1-LG5 were overexpressed in Chinese hamster ovary cells and purified
      by heparin chromatography. alpha 1LG1-LG5 and alpha 4LG1-LG5 eluted at NaCl
      concentrations of 0.30 and 0.47 m, respectively. In solid phase binding assays
      with immobilized heparin, half-maximal concentrations of 14 (alpha 1LG1-LG5) and
      1.4 nm (alpha 4LG1-LG5) were observed. N-Glycan cleavage of alpha 4LG1-LG5 did
      not affect affinity to heparin. The affinity of alpha 4LG1-LG5 was significantly
      reduced upon denaturation with 8 m urea but could be recovered by removing urea.
      Chymotrypsin digestion of alpha 4LG1-LG5 yielded high and low heparin affinity
      fragments containing either the alpha 4LG4-LG5 or alpha 4LG2-LG3 modules,
      respectively. Trypsin digestion of heparin-bound alpha 4LG1-LG5 yielded a high
      affinity fragment of about 190 residues corresponding to the alpha 4LG4 module
      indicating that the high affinity binding site is contained within alpha 4LG4.
      Competition for heparin binding of synthetic peptides covering the alpha 4LG4
      region with complete alpha 4LG1-LG5 suggests that the sequence AHGRL1521 is
      crucial for high affinity binding. Introduction of mutation of H1518A or R1520A
      in glutathione S-transferase fusion protein of the alpha 4LG4 module produced in
      Escherichia coli markedly reduced heparin binding activity of the wild type. When
      compared with the known structure of alpha 2LG5, this sequence corresponds to the
      turn connecting strands E and F of the 14-stranded beta-sheet sandwich, which is
      opposite to the proposed binding sites for calcium ion, alpha-dystroglycan, and
      heparan sulfate.

PMID- 10893233
TI  - Delayed reversal of shape change in cells expressing FP(B) prostanoid receptors.
      Possible role of receptor resensitization.
AB  - Prostaglandin F(2 alpha) (PGF(2 alpha)) receptors are G-protein-coupled receptors
      consisting of two alternative mRNA splice variants, named FP(A) and FP(B). As
      compared with the FP(A) isoform, the FP(B) isoform lacks the last 46 amino acids
      of the carboxyl terminus and, therefore, represents a truncated version of the
      FP(A). We recently found (Pierce, K. L., Fujino, H., Srinivasan, D., and Regan,
      J. W. (1999) J. Biol. Chem. 274, 35944-35949) that stimulation of both isoforms
      with PGF(2 alpha) leads to activation of a Rho signaling pathway, resulting in
      tyrosine phosphorylation of p125 focal adhesion kinase, formation of actin stress
      fibers, and cell rounding. Although the activation of Rho and subsequent cell
      rounding occur at a similar rate for both isoforms, we now report that following
      the removal of PGF(2 alpha) the reversal of cell rounding is much slower for
      cells expressing the FP(B) isoform as compared with the FP(A) isoform. Thus, in
      HEK-293 cells that stably express the FP(A) isoform, the reversal of cell
      rounding appears to be complete after 1 h, whereas for FP(B)-expressing cells
      there is essentially no reversal even after 2 h. Similarly, the disappearance of
      stress fibers and dephosphorylation of p125 focal adhesion kinase following
      removal of agonist are much slower in FP(B)-expressing cells than in FP(A)
      expressing cells. The mechanism of this differential reversal appears to involve
      a difference in receptor resensitization following the removal of agonist. Based
      upon whole cell radioligand binding, agonist-induced stimulation of inositol
      phosphate formation, and mobilization of intracellular Ca(2+), the FP(B) isoform
      resensitizes more slowly than the FP(A) isoform. These findings suggest that the
      carboxyl terminus of the FP(A) is critical for resensitization and that the
      slower resensitization of the FP(B) isoform leads to prolonged signaling. This
      differential signaling distinguishes the FP(A) and FP(B) receptor isoforms and
      could be important toward understanding the physiological actions of PGF(2
      alpha).

PMID- 10893234
TI  - The chemistry of the reaction determines the invariant amino acids during the
      evolution and divergence of orotidine 5'-monophosphate decarboxylase.
AB  - Orotidine 5'-phosphate (OMP) decarboxylase has the largest rate enhancement for
      any known enzyme. For an average protein of 270 amino acids from more than 80
      species, only 8 amino acids are invariant, and 7 of these correspond to ligand
      binding residues in the crystal structures of the enzyme from four species. It
      appears that the chemistry required for catalysis determines the invariant
      residues for this enzyme structure. A motif of three invariant amino acids at the
      catalytic site (DXKXXD) is also found in the enzyme hexulose-phosphate synthase.
      Although the core of OMP decarboxylase is conserved, it has undergone a variety
      of changes in subunit size or fusion to other protein domains, such as orotate
      phosphoribosyltransferase, during evolution in different kingdoms. The phylogeny
      of OMP decarboxylase shows a unique subgroup distinct from the three kingdoms of
      life. The enzyme subunit size almost doubles from Archaea (average mass of 24.5
      kDa) to certain fungi (average mass of 41.7 kDa). These observed changes in
      subunit size are produced by insertions at 12 sites, largely in loops and on the
      exterior of the core protein. The consensus for all sequences has a minimal size
      of <20 kDa.

PMID- 10893235
TI  - Protease-activated receptor-1 down-regulation: a mutant HeLa cell line suggests
      novel requirements for PAR1 phosphorylation and recruitment to clathrin-coated
      pits.
AB  - Protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for
      thrombin, is irreversibly activated by a proteolytic mechanism, then internalized
      and degraded in lysosomes. The latter is critical for temporal fidelity of
      thrombin signaling. Toward understanding PAR1 down-regulation, we first
      investigated the pathway of PAR1 internalization. Activated PAR1 was rapidly
      recruited to clathrin-coated pits, where it colocalized with transferrin receptor
      (TfnR). Dominant-negative dynamin and clathrin hub mutants both blocked PAR1
      internalization. Blockade of PAR1 internalization with dynamin K44A also
      inhibited activation-dependent PAR1 degradation. Thus activated PAR1 internalizes
      via clathrin-coated pits together with receptors that recycle and is then sorted
      away from such receptors and delivered to lysosomes. In the course of these
      studies we identified a mutant HeLa cell line, designated JT1, that was defective
      in PAR1 internalization. PAR1 signaled robustly in JT1 cells but was not
      phosphorylated or recruited to clathrin-coated pits after activation.
      Internalization of TfnR was intact in JT1 cells and internalization of beta(2)
      adrenergic receptor, a GPCR that internalizes and recycles, was present but
      perhaps reduced. Taken together, these studies suggest that PAR1 is internalized
      in a dynamin- and clathrin-dependent manner like TfnR and beta(2)-adrenergic
      receptor but requires a distinct gene product for recruitment into this pathway.

PMID- 10893236
TI  - Estrogen targets genes involved in protein processing, calcium homeostasis, and
      Wnt signaling in the mouse uterus independent of estrogen receptor-alpha and 
      beta.
AB  - Estrogen actions in target organs are normally mediated via activation of nuclear
      estrogen receptors (ERs). By using mRNA differential display technique, we show,
      herein, that estradiol-17beta (E(2)) and its catechol metabolite 4-hydroxy-E(2)
      (4OHE(2)) can modulate uterine gene expression in ERalpha(-/-) mice. Whereas
      administration of E(2) or 4OHE(2) rapidly up-regulated (4-8-fold) the expression
      of immunoglobulin heavy chain binding protein (Bip), calpactin I (CalP),
      calmodulin (CalM), and Sik similar protein (Sik-SP) genes in ovariectomized wild
      type or ERalpha(-/-) mice, the expression of secreted frizzled related protein-2
      (SFRP-2) gene was down-regulated (4-fold). Bip, CalP, and CalM are calcium
      binding proteins and implicated in calcium homeostasis, whereas SFRP-2 is a
      negative regulator of Wnt signaling. Bip and Sik-SP also possess chaperone-like
      functions. Administration of ICI-182,780 or cycloheximide failed to influence
      these estrogenic responses, demonstrating that these effects occur independent of
      ERalpha, ERbeta, or protein synthesis. In situ hybridization showed differential
      cell-specific expression of these genes in wild-type and ERalpha(-/-) uteri.
      Although progesterone can antagonize or synergize estrogen actions, it had
      minimal effects on these estrogenic responses. Collectively, the results
      demonstrate that estrogens have a unique ability to influence specific genes in
      the uterus not involving classical nuclear ERs.

PMID- 10893237
TI  - Molecular mechanism of the inhibition of phospholipase C beta 3 by protein kinase
      C.
AB  - Activation of protein kinase C (PKC) can result from stimulation of the receptor
      G protein-phospholipase C (PLCbeta) pathway. In turn, phosphorylation of PLCbeta
      by PKC may play a role in the regulation of receptor-mediated
      phosphatidylinositide (PI) turnover and intracellular Ca(2+) release. Activation
      of endogenous PKC by phorbol 12-myristate 13-acetate inhibited both Galpha(q)
      coupled (oxytocin and M1 muscarinic) and Galpha(i)-coupled (formyl-Met-Leu-Phe)
      receptor-stimulated PI turnover by 50-100% in PHM1, HeLa, COSM6, and RBL-2H3
      cells expressing PLCbeta(3). Activation of conventional PKCs with thymeleatoxin
      similarly inhibited oxytocin or formyl-Met-Leu-Phe receptor-stimulated PI
      turnover. The PKC inhibitory effect was also observed when PLCbeta(3) was
      stimulated directly by Galpha(q) or Gbetagamma in overexpression assays. PKC
      phosphorylated PLCbeta(3) at the same predominant site in vivo and in vitro.
      Peptide sequencing of in vitro phosphorylated recombinant PLCbeta(3) and site
      directed mutagenesis identified Ser(1105) as the predominant phosphorylation
      site. Ser(1105) is also phosphorylated by protein kinase A (PKA; Yue, C., Dodge,
      K. L., Weber, G., and Sanborn, B. M. (1998) J. Biol. Chem. 273, 18023-18027).
      Similar to PKA, the inhibition by PKC of Galpha(q)-stimulated PLCbeta(3) activity
      was completely abolished by mutation of Ser(1105) to Ala. In contrast, mutation
      of Ser(1105) or Ser(26), another putative phosphorylation target, to Ala had no
      effect on inhibition of Gbetagamma-stimulated PLCbeta(3) activity by PKC or PKA.
      These data indicate that PKC and PKA act similarly in that they inhibit Galpha(q)
      stimulated PLCbeta(3) as a result of phosphorylation of Ser(1105). Moreover, PKC
      and PKA both inhibit Gbetagamma-stimulated activity by mechanisms that do not
      involve Ser(1105).

PMID- 10893238
TI  - Crystal structure of TRAIL-DR5 complex identifies a critical role of the unique
      frame insertion in conferring recognition specificity.
AB  - TRAIL is a cytokine that induces apoptosis in a wide variety of tumor cells but
      rarely in normal cells. It contains an extraordinarily elongated loop because of
      an unique insertion of 12-16 amino acids compared with the other members of tumor
      necrosis factor family. Biological implication of the frame insertion has not
      been clarified. We have determined the crystal structure of TRAIL in a complex
      with the extracellular domain of death receptor DR5 at 2.2 A resolution. The
      structure reveals extensive contacts between the elongated loop and DR5 in an
      interaction mode that would not be allowed without the frame insertion. These
      interactions are missing in the structures of the complex determined by others
      recently. This observation, along with structure-inspired deletion analysis,
      identifies the critical role of the frame insertion as a molecular strategy
      conferring specificity upon the recognition of cognate receptors. The structure
      also suggests that a built-in flexibility of the tumor necrosis factor receptor
      family members is likely to play a general and important role in the binding and
      recognition of tumor necrosis factor family members.

PMID- 10893239
TI  - Differences between cystic fibrosis transmembrane conductance regulator and HisP
      in the interaction with the adenine ring of ATP.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is a
      member of the ATP-binding cassette transporter family. The most conserved
      features of this family are the nucleotide-binding domains. As in other members
      of this family, these domains bind and hydrolyze ATP; in CFTR this opens and
      closes the channel pore. The recent crystal structures of related bacterial
      transporters show that an aromatic residue interacts with the adenine ring of ATP
      to stabilize nucleotide binding. CFTR contains six aromatic residues that are
      candidates to coordinate the nucleotide base. We mutated each to cysteine and
      examined the functional consequences. None of the mutations disrupted channel
      function or the ability to discriminate between ATP, GTP, and CTP. We also
      applied [2-(triethylammonium)ethyl] methanethiosulfonate to covalently modify the
      introduced cysteines. The mutant channels CFTR-F429C, F430C, F433C, and F1232C
      showed no difference from wild-type CFTR, indicating that either the residues
      were not accessible to modification, or cysteine modification did not affect
      function. Although modification inactivated CFTR-Y1219C more rapidly than wild
      type CFTR, and inactivation of CFTR-F446C was nucleotide-dependent; failure of
      these mutations to alter gating suggested that Tyr(1219) and Phe(446) were not
      important for nucleotide binding. The results suggest that ATP binding may not
      involve the coordination of the adenine ring by an aromatic residue analogous to
      that in some bacterial transporters. Taken together with earlier work, this study
      points to a model in which most of the binding energy for ATP is contributed by
      the phosphate groups.

PMID- 10893240
TI  - Different binding properties and affinities for ATP and ADP among sulfonylurea
      receptor subtypes, SUR1, SUR2A, and SUR2B.
AB  - ATP-sensitive potassium (K(ATP)) channels, composed of sulfonylurea receptor
      (SURx) and Kir6.x, play important roles by linking cellular metabolic state to
      membrane potential in various tissues. Pancreatic, cardiac, and vascular smooth
      muscle K(ATP) channels, which consist of different subtypes of SURx, differ in
      their responses to cellular metabolic state. To explore the possibility that
      different interactions of SURx with nucleotides cause differential regulation of
      K(ATP) channels, we analyzed the properties of nucleotide-binding folds (NBFs) of
      SUR1, SUR2A, and SUR2B. SURx in crude membrane fractions was incubated with 8
      azido-[alpha-(32)P]ATP or 8-azido-[gamma-(32)P]ATP under various conditions and
      was photoaffinity-labeled. Then, SURx was digested mildly with trypsin, and
      partial tryptic fragments were immunoprecipitated with antibodies against NBF1
      and NBF2. Some nucleotide-binding properties were different among SUR subtypes as
      follows. 1) Mg(2+) dependence of nucleotide binding of NBF2 of SUR1 was high,
      whereas those of SUR2A and SUR2B were low. 2) The affinities of NBF1 of SUR1 for
      ATP and ADP, especially for ATP, were significantly higher than those of SUR2A
      and SUR2B. 3) The affinities of NBF2 of SUR2B for ATP and ADP were significantly
      higher than those of SUR2A. This is the first biochemical study to analyze and
      compare the nucleotide-binding properties of NBFs of three SUR subtypes, and our
      results suggest that their different properties may explain, in part, the
      differential regulation of K(ATP) channel subtypes. The high nucleotide-binding
      affinities of SUR1 may explain the high ability of SUR1 to stimulate pancreatic
      K(ATP) channels. It is also suggested that the C-terminal 42 amino acids affect
      the physiological roles of SUR2A and SUR2B by changing the nucleotide-binding
      properties of their NBFs.

PMID- 10893241
TI  - Calmodulin binds to and inhibits the activity of the membrane distal catalytic
      domain of receptor protein-tyrosine phosphatase alpha.
AB  - cDNA expression library screening revealed binding between the membrane distal
      catalytic domain (D2) of protein-tyrosine phosphatase alpha (PTPalpha) and
      calmodulin. Characterization using surface plasmon resonance showed that
      calmodulin bound to PTPalpha-D2 in a Ca(2+)-dependent manner but did not bind to
      the membrane proximal catalytic domain (D1) of PTPalpha, to the two tandem
      catalytic domains (D1D2) of PTPalpha, nor to the closely related D2 domain of
      PTPepsilon. Calmodulin bound to PTPalpha-D2 with high affinity, exhibiting a K(D)
      approximately 3 nm. The calmodulin-binding site was localized to amino acids 520
      538 in the N-terminal region of D2. Site-directed mutagenesis showed that Lys-521
      and Asn-534 were required for optimum calmodulin binding and that restoration of
      these amino acids to the counterpart PTPepsilon sequence could confer calmodulin
      binding. The overlap of the binding site with the predicted lip of the catalytic
      cleft of PTPalpha-D2, in conjunction with the observation that calmodulin acts as
      a competitive inhibitor of D2-catalyzed dephosphorylation (K(i) approximately 340
      nm), suggests that binding of calmodulin physically blocks or distorts the
      catalytic cleft of PTPalpha-D2 to prevent interaction with substrate. When
      expressed in cells, full-length PTPalpha and PTPalpha lacking only D1, but not
      full-length PTPepsilon, bound to calmodulin beads in the presence of Ca(2+).
      Also, PTPalpha was found in association with calmodulin immunoprecipitated from
      cell lysates. Thus calmodulin does associate with PTPalpha in vivo but not with
      PTPalpha-D1D2 in vitro, highlighting a potential conformational difference
      between these forms of the tandem catalytic domains. The above findings suggest
      that calmodulin is a possible specific modulator of PTPalpha-D2 and, via D2, of
      PTPalpha.

PMID- 10893242
TI  - A targeted apolipoprotein B-38.9-producing mutation causes fatty livers in mice
      due to the reduced ability of apolipoprotein B-38.9 to transport triglycerides.
AB  - Nonphysiological truncations of apolipoprotein (apo) B-100 cause familial
      hypobetalipoproteinemia (FHBL) in humans and mice. An elucidation of the
      mechanisms underlying the FHBL phenotypes may provide valuable information on the
      metabolism of apo B-containing lipoproteins and the structure-function
      relationship of apo B. To generate a faithful mouse model of human FHBL, a subtle
      mutation was introduced into the mouse apo B gene by targeting embryonic stem
      cells using homologous recombination followed by removal of the selection marker
      gene by Cre-loxP-mediated site-specific recombination. The engineered mice bear a
      premature stop codon at residue 1767 and a 42-base pair loxP inserted into intron
      24 of the apo B gene, thus closely resembling the apo B-38.9-producing mutation
      in humans. Apo B-38.9 was the sole apo B protein in homozygote (apob(38.9/38.9))
      plasma. In heterozygotes (apob(+/)(38. 9)), apo B-100 and apo B-48 were reduced
      by 75 and 40%, respectively, and apo B-38.9 represented 20% of total circulating
      apo B. Hepatic apo B-38.9 mRNA levels were reduced by 40%. In cultured
      apob(+/)(38. 9) hepatocytes, apo B-100 was produced in trace quantities, and the
      synthesis rate of apo B-38.9 relative to apo B-48 was reduced by 40%. However,
      almost equimolar amounts of apo B-38.9 and apo B-48 were secreted into the media.
      Pulse-chase studies revealed that apo B-38. 9 was secreted at a faster rate and
      more efficiently than apoB-48. Nevertheless, both apob(+/)(38.9) and
      apob(38.9/38.9) mice had reduced hepatic triglyceride secretion rates and fatty
      livers. Thus, low mRNA levels or defective secretion of apo B-38.9 may not be
      responsible for the FHBL phenotypes caused by the apo B-38.9 mutation. Rather, a
      reduced capacity of apo B-38.9 for triglyceride transport may account for the
      fatty livers in these mice.

PMID- 10893243
TI  - Transcriptional regulation of the mouse cytosolic chaperonin subunit gene Ccta/t
      complex polypeptide 1 by selenocysteine tRNA gene transcription activating factor
      family zinc finger proteins.
AB  - The chaperonin containing t-complex polypeptide 1 (CCT) is a molecular chaperone
      assisting in the folding of proteins in eukaryotic cytosol, and the Ccta
      (encoding the alpha subunit of CCT)/t-complex polypeptide 1 gene encodes the
      alpha subunit of CCT. We show here that transcription of the mouse Ccta gene is
      regulated by selenocysteine tRNA gene transcription activating factor (Staf)
      family zinc-finger transcription factors ZNF143 and ZNF76. Reporter gene assay
      using HeLa cells indicated that the Ccta gene promoter contains two 18-base pair
      long cis-acting elements with similar sequences at -70 and -20 base pairs
      (designated CCT alpha subunit gene transcription activating element 1 (CAE1) and
      CAE2, respectively). By yeast one-hybrid screening of CAE1-binding factors, we
      isolated human ZNF143, which is known to activate transcription of selenocysteine
      tRNA and small nuclear RNA genes. DNA binding domains of ZNF143 and ZNF76
      produced in E. coli recognized CAE1 and CAE2 elements in electrophoretic mobility
      shift assay. HeLa cell nuclear extract contained a protein that specifically
      binds to CAE1 and CAE2 and recognized by anti-ZNF143 antibody. Transcription from
      a minimal Ccta promoter containing CAE2 element in HeLa cells was enhanced by
      overexpression of full-length ZNF143 and ZNF76 but inhibited by that of their DNA
      binding domains alone. These results demonstrate that the Staf family proteins
      control transcription of at least one of the chaperone-encoding genes besides
      that of tRNA and small nuclear RNA genes. These RNA and chaperone genes are
      suggested to be coregulated to facilitate synthesis of mature proteins during
      active cell growth.

PMID- 10893244
TI  - Cloning of the cDNAs coding for two novel molybdo-flavoproteins showing high
      similarity with aldehyde oxidase and xanthine oxidoreductase.
AB  - The cDNAs coding for two novel mouse molybdo-flavoproteins, AOH1 and AOH2
      (aldehyde oxidase homolog 1 and 2), were isolated. The AOH1 and AOH2 cDNAs code
      for polypeptides of 1336 amino acids. The two proteins have similar primary
      structure and show striking amino acid identity with aldehyde oxidase and
      xanthine oxidoreductase, two other molybdo-flavoenzymes. AOH1 and AOH2 contain
      consensus sequences for a molybdopterin-binding site and two distinct 2Fe-2S
      redox centers. In its native conformation, AOH1 has a molecular weight consistent
      with a homotetrameric structure. Transfection of the AOH1 and AOH2 cDNAs results
      in the production of proteins with phenanthridine but not hypoxanthine oxidizing
      activity. Furthermore, the AOH1 protein has benzaldehyde oxidizing activity with
      electrophoretic characteristics identical to those of a previously identified
      aldehyde oxidase isoenzyme (Holmes, R. S. (1979) Biochem. Genet. 17, 517-528).
      The AOH1 transcript is expressed in the hepatocytes of the adult and fetal liver
      and in spermatogonia. In liver, the AOH1 protein is synthesized in a gender
      specific fashion. The expression of AOH2 is limited to keratinized epithelia and
      the basal layer of the epidermis and hair folliculi. The selective cell and
      tissue distribution of AOH1 and AOH2 mRNAs is consistent with the localization of
      the respective protein products.

PMID- 10893245
TI  - alpha 2A/alpha 2C-adrenergic receptor third loop chimera show that agonist
      interaction with receptor subtype backbone establishes G protein-coupled receptor
      kinase phosphorylation.
AB  - The alpha(2A)-adrenergic receptor (AR) undergoes rapid agonist-promoted
      desensitization due to phosphorylation by G protein-coupled receptor kinases
      (GRKs) 2 and 3 at serines in the third intracellular loop of the receptor. In
      contrast, the alpha(2C)AR fails to display such desensitization or
      phosphorylation, which has been presumed to be due to this receptor lacking GRK
      phosphorylation sites. However, the alpha(2C)AR has multiple serines and
      threonines in putative favorable motifs within its third intracellular loop. We
      considered that the conformation of the third intracellular loop imposed by
      agonists binding to the transmembrane-spanning domains could be the basis of this
      subtype-specific property, rather than the presence or absence of
      phosphoacceptors per se. To address this, alpha(2A)/alpha(2C) third loop chimeric
      receptors were constructed. In whole cell phosphorylation studies, the alpha(2A)
      with the alpha(2C) third loop receptor underwent agonist-promoted phosphorylation
      while the alpha(2C) with the alpha(2A) third loop receptor did not, indicating
      that the agonist interaction with the parent receptor backbone establishes the
      phosphorylation phenotype. We postulated then that agonists with diverse
      structures that distinctly interact with alpha(2)AR should display different
      degrees of phosphorylation independent of receptor activation. Indeed, several
      full and partial agonists were identified, which evoked phosphorylation that was
      not related to intrinsic activity as established by [(35)S]guanosine 5'-3-O
      (thio)triphosphate binding. Taken together, it appears that phosphorylation of
      the alpha(2)AR evoked by agonist is highly sensitive to the conformation of the
      third intracellular loop induced/stabilized by agonist to such an extent that
      these properties dictate the extent of phosphorylation of the loop when
      phosphoacceptors are present, and are the basis for subtype-specific
      phosphorylation.

PMID- 10893246
TI  - Probing the structure of the nicotinic acetylcholine receptor with 4
      benzoylbenzoylcholine, a novel photoaffinity competitive antagonist.
AB  - [(3)H]4-Benzoylbenzoylcholine (Bz(2)choline) was synthesized as a photoaffinity
      probe for the Torpedo nicotinic acetylcholine receptor (nAChR).
      [(3)H]Bz(2)choline acts as an nAChR competitive antagonist and binds at
      equilibrium with the same affinity (K(D) = 1.4 microm) to both agonist sites.
      Irradiation at 320 nm of nAChR-rich membranes equilibrated with
      [(3)H]Bz(2)choline results in the covalent incorporation of [(3)H]Bz(2)choline
      into the nAChR gamma- and delta-subunits that is inhibitable by agonist, with
      little specific incorporation in the alpha-subunits. To identify the sites of
      photoincorporation, gamma- and delta-subunits, isolated from nAChR-rich membranes
      photolabeled with [(3)H]Bz(2)choline, were digested enzymatically, and the
      labeled fragments were isolated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and/or reversed-phase high performance liquid chromatography. For
      the gamma-subunit, Staphylococcus aureus V8 protease produced a specifically
      labeled peptide beginning at gammaVal-102, whereas for the delta-subunit,
      endoproteinase Asp-N produced a labeled peptide beginning at deltaAsp-99. Amino
      terminal sequence analysis identified the homologous residues gammaLeu-109 and
      deltaLeu-111 as the primary sites of [(3)H]Bz(2)choline photoincorporation. This
      is the first identification by affinity labeling of non-reactive amino acids
      within the acetylcholine-binding sites, and these results establish that when
      choline esters of benzoic acid are bound to the nAChR agonist sites, the para
      substituent is selectively oriented toward and in proximity to amino acids
      gammaLeu-109/deltaLeu-111.

PMID- 10893247
TI  - The multidrug resistance protein 5 functions as an ATP-dependent export pump for
      cyclic nucleotides.
AB  - Cellular export of cyclic nucleotides has been observed in various tissues and
      may represent an elimination pathway for these signaling molecules, in addition
      to degradation by phosphodiesterases. In the present study we provide evidence
      that this export is mediated by the multidrug resistance protein isoform MRP5
      (gene symbol ABCC5). The transport function of MRP5 was studied in V79 hamster
      lung fibroblasts transfected with a human MRP5 cDNA. An MRP5-specific antibody
      detected an overexpression of the glycoprotein of 185 +/- 15 kDa in membranes
      from MRP5-transfected cells and a low basal expression of hamster Mrp5 in control
      membranes. ATP-dependent transport of 3',5'-cyclic GMP at a substrate
      concentration of 1 micrometer was 4-fold higher in membrane vesicles from MRP5
      transfected cells than in control membranes. This transport was saturable with a
      K(m) value of 2.1 micrometer. MRP5-mediated transport was also detected for 3',5'
      cyclic AMP at a lower affinity, with a K(m) value of 379 micrometer. A potent
      inhibition of MRP5-mediated transport was observed by several compounds, known as
      phosphodiesterase modulators, including trequinsin, with a K(i) of 240 nm, and
      sildenafil, with a K(i) value of 267 nm. Thus, cyclic nucleotides are
      physiological substrates for MRP5; moreover, MRP5 may represent a novel
      pharmacological target for the enhancement of tissue levels of cGMP.

PMID- 10893248
TI  - Duplicated downstream enhancers control expression of the human apolipoprotein E
      gene in macrophages and adipose tissue.
AB  - Two distal enhancers that specify apolipoprotein (apo) E gene expression in
      isolated macrophages and adipose tissue were identified in transgenic mice that
      were generated with constructs of the human apoE/C-I/C-I'/C-IV/C-II gene cluster.
      One of these enhancers, multienhancer 1, consists of a 620-nucleotide sequence
      located 3.3 kilobases (kb) downstream of the apoE gene. The second enhancer,
      multienhancer 2, is a 619-nucleotide sequence located 15.9 kb downstream of the
      apoE gene and 5.9 kb downstream of the apoC-I gene. The two enhancers are 95%
      identical in sequence, and they are likely to have arisen as a consequence of the
      gene duplication event that yielded the apoC-I gene and the apoC-I' pseudogene.
      Both enhancer sequences appear to have equivalent activity in directing apoE gene
      expression in peritoneal macrophages and in adipocytes, suggesting that their
      activity in specific cell types may be determined by common regulatory elements.

PMID- 10893249
TI  - CENP-meta, an essential kinetochore kinesin required for the maintenance of
      metaphase chromosome alignment in Drosophila.
AB  - CENP-meta has been identified as an essential, kinesin-like motor protein in
      Drosophila. The 257-kD CENP-meta protein is most similar to the vertebrate
      kinetochore-associated kinesin-like protein CENP-E, and like CENP-E, is shown to
      be a component of centromeric/kinetochore regions of Drosophila chromosomes.
      However, unlike CENP-E, which leaves the centromere/kinetochore region at the end
      of anaphase A, the CENP-meta protein remains associated with the
      centromeric/kinetochore region of the chromosome during all stages of the
      Drosophila cell cycle. P-element-mediated disruption of the CENP-meta gene leads
      to late larval/pupal stage lethality with incomplete chromosome alignment at
      metaphase. Complete removal of CENP-meta from the female germline leads to
      lethality in early embryos resulting from defects in metaphase chromosome
      alignment. Real-time imaging of these mutants with GFP-labeled chromosomes
      demonstrates that CENP-meta is required for the maintenance of chromosomes at the
      metaphase plate, demonstrating that the functions required to establish and
      maintain chromosome congression have distinguishable requirements.

PMID- 10893253
TI  - AAA proteins. Lords of the ring.

PMID- 10893252
TI  - Mitotic transcription repression in vivo in the absence of nucleosomal chromatin
      condensation.
AB  - All nuclear RNA synthesis is repressed during the mitotic phase of the cell
      cycle. In addition, RNA polymerase II (RNAP II), nascent RNA and many
      transcription factors disengage from DNA during mitosis. It has been proposed
      that mitotic transcription repression and disengagement of factors are due to
      either mitotic chromatin condensation or biochemical modifications to the
      transcription machinery. In this study, we investigate the requirement for
      chromatin condensation in establishing mitotic transcription repression and
      factor loss, by analyzing transcription and RNAP II localization in mitotic cells
      infected with herpes simplex virus type 1. We find that virus-infected cells
      enter mitosis and that mitotic viral DNA is maintained in a nucleosome-free and
      noncondensed state. Our data show that RNAP II transcription is repressed on
      cellular genes that are condensed into mitotic chromosomes and on viral genes
      that remain nucleosome free and noncondensed. Although RNAP II may interact
      indirectly with viral DNA during mitosis, it remains transcriptionally unengaged.
      This study demonstrates that mitotic repression of transcription and loss of
      transcription factors from mitotic DNA can occur independently of nucleosomal
      chromatin condensation.

PMID- 10893254
TI  - Transcription factor ERG variants and functional diversification of chondrocytes
      during limb long bone development.
AB  - During limb development, chondrocytes located at the epiphyseal tip of long bone
      models give rise to articular tissue, whereas the more numerous chondrocytes in
      the shaft undergo maturation, hypertrophy, and mineralization and are replaced by
      bone cells. It is not understood how chondrocytes follow these alternative
      pathways to distinct fates and functions. In this study we describe the cloning
      of C-1-1, a novel variant of the ets transcription factor ch-ERG. C-1-1 lacks a
      short 27-amino acid segment located approximately 80 amino acids upstream of the
      ets DNA binding domain. We found that in chick embryo long bone anlagen, C-1-1
      expression characterizes developing articular chondrocytes, whereas ch-ERG
      expression is particularly prominent in prehypertrophic chondrocytes in the
      growth plate. To analyze the function of C-1-1 and ch-ERG, viral vectors were
      used to constitutively express each factor in developing chick leg buds and
      cultured chondrocytes. We found that virally driven expression of C-1-1
      maintained chondrocytes in a stable and immature phenotype, blocked their
      maturation into hypertrophic cells, and prevented the replacement of cartilage
      with bone. It also induced synthesis of tenascin-C, an extracellular matrix
      protein that is a unique product of developing articular chondrocytes. In
      contrast, virally driven expression of ch-ERG significantly stimulated
      chondrocyte maturation in culture, as indicated by increases in alkaline
      phosphatase activity and deposition of a mineralized matrix; however, it had
      modest effects in vivo. The data show that C-1-1 and ch-ERG have diverse
      biological properties and distinct expression patterns during skeletogenesis, and
      are part of molecular mechanisms by which limb chondrocytes follow alternative
      developmental pathways. C-1-1 is the first transcription factor identified to
      date that appears to be instrumental in the genesis and function of epiphyseal
      articular chondrocytes.

PMID- 10893255
TI  - Reduced mobility of the alternate splicing factor (ASF) through the nucleoplasm
      and steady state speckle compartments.
AB  - Compartmentalization of the nucleus is now recognized as an important level of
      regulation influencing specific nuclear processes. The mechanism of factor
      organization and the movement of factors in nuclear space have not been fully
      determined. Splicing factors, for example, have been shown to move in a directed
      manner as large intact structures from sites of concentration to sites of active
      transcription, but splicing factors are also thought to exist in a freely
      diffusible state. In this study, we examined the movement of a splicing factor,
      ASF, green fluorescent fusion protein (ASF-GFP) using time-lapse microscopy and
      the technique fluorescence recovery after photobleaching (FRAP). We find that ASF
      GFP moves at rates up to 100 times slower than free diffusion when it is
      associated with speckles and, surprisingly, also when it is dispersed in the
      nucleoplasm. The mobility of ASF is consistent with frequent but transient
      interactions with relatively immobile nuclear binding sites. This mobility is
      slightly increased in the presence of an RNA polymerase II transcription
      inhibitor and the ASF molecules further enrich in speckles. We propose that the
      nonrandom organization of splicing factors reflects spatial differences in the
      concentration of relatively immobile binding sites.

PMID- 10893256
TI  - Role of the cytoplasmic segments of Sec61alpha in the ribosome-binding and
      translocation-promoting activities of the Sec61 complex.
AB  - The Sec61 complex performs a dual function in protein translocation across the
      RER, serving as both the high affinity ribosome receptor and the translocation
      channel. To define regions of the Sec61 complex that are involved in ribosome
      binding and translocation promotion, ribosome-stripped microsomes were subjected
      to limited digestions using proteases with different cleavage specificities.
      Protein immunoblot analysis using antibodies specific for the NH(2) and COOH
      terminus of Sec61alpha was used to map the location of proteolysis cleavage
      sites. We observed a striking correlation between the loss of binding activity
      for nontranslating ribosomes and the digestion of the COOH- terminal tail or
      cytoplasmic loop 8 of Sec61alpha. The proteolyzed microsomes were assayed for SRP
      independent translocation activity to determine whether high affinity binding of
      the ribosome to the Sec61 complex is a prerequisite for nascent chain transport.
      Microsomes that do not bind nontranslating ribosomes at physiological ionic
      strength remain active in SRP-independent translocation, indicating that the
      ribosome binding and translocation promotion activities of the Sec61 complex do
      not strictly correlate. Translocation-promoting activity was most severely
      inhibited by cleavage of cytosolic loop 6, indicating that this segment is a
      critical determinant for this function of the Sec61 complex.

PMID- 10893257
TI  - The heat shock protein Ssa2p is required for import of fructose-1, 6
      bisphosphatase into Vid vesicles.
AB  - Fructose-1,6-bisphosphatase (FBPase) is targeted to the vacuole for degradation
      when Saccharomyces cerevisiae are shifted from low to high glucose. Before
      vacuolar import, however, FBPase is sequestered inside a novel type of vesicle,
      the vacuole import and degradation (Vid) vesicles. Here, we reconstitute import
      of FBPase into isolated Vid vesicles. FBPase sequestration into Vid vesicles
      required ATP and cytosol, but was inhibited if ATP binding proteins were depleted
      from the cytosol. The heat shock protein Ssa2p was identified as one of the ATP
      binding proteins involved in FBPase import. A Deltassa2 strain exhibited a
      significant decrease in the rate of FBPase degradation in vivo as compared with
      Deltassa1, Deltassa3, or Deltassa4 strains. Likewise, in vitro import was
      impaired for the Deltassa2 strain, but not for the other Deltassa strains. The
      cytosol was identified as the site of the Deltassa2 defect; Deltassa2 cytosol did
      not stimulate FBPase import into import competent Vid vesicles, but wild-type
      cytosol supported FBPase import into competent Deltassa2 vesicles. The addition
      of purified recombinant Ssa2p stimulated FBPase import into Deltassa2 Vid
      vesicles, providing Deltassa2 cytosol was present. Thus, Ssa2p, as well as other
      undefined cytosolic proteins are required for the import of FBPase into vesicles.

PMID- 10893258
TI  - The unfolded protein response regulates multiple aspects of secretory and
      membrane protein biogenesis and endoplasmic reticulum quality control.
AB  - The unfolded protein response (UPR) is an intracellular signaling pathway that
      relays signals from the lumen of the ER to activate target genes in the nucleus.
      We devised a genetic screen in the yeast Saccharomyces cerevisiae to isolate
      mutants that are dependent on activation of the pathway for viability. Using this
      strategy, we isolated mutants affecting various aspects of ER function, including
      protein translocation, folding, glycosylation, glycosylphosphatidylinositol
      modification, and ER-associated protein degradation (ERAD). Extending results
      gleaned from the genetic studies, we demonstrate that the UPR regulates
      trafficking of proteins at the translocon to balance the needs of biosynthesis
      and ERAD. The approach also revealed connections of the UPR to other regulatory
      pathways. In particular, we identified SON1/RPN4, a recently described
      transcriptional regulator for genes encoding subunits of the proteasome. Our
      genetic strategy, therefore, offers a powerful means to provide insight into the
      physiology of the UPR and to identify novel genes with roles in many aspects of
      secretory and membrane protein biogenesis.

PMID- 10893259
TI  - Molecular basis for Rab prenylation.
AB  - Rab escort proteins (REP) 1 and 2 are closely related mammalian proteins required
      for prenylation of newly synthesized Rab GTPases by the cytosolic heterodimeric
      Rab geranylgeranyl transferase II complex (RabGG transferase). REP1 in mammalian
      cells is the product of the choroideremia gene (CHM). CHM/REP1 deficiency in
      inherited disease leads to degeneration of retinal pigmented epithelium and loss
      of vision. We now show that amino acid residues required for Rab recognition are
      critical for function of the yeast REP homologue Mrs6p, an essential protein that
      shows 50% homology to mammalian REPs. Mutant Mrs6p unable to bind Rabs failed to
      complement growth of a mrs6Delta null strain and were found to be dominant
      inhibitors of growth in a wild-type MRS6 strain. Mutants were identified that did
      not affect Rab binding, yet prevented prenylation in vitro and failed to support
      growth of the mrs6Delta null strain. These results suggest that in the absence of
      Rab binding, REP interaction with RabGG transferase is maintained through Rab
      independent binding sites, providing a molecular explanation for the kinetic
      properties of Rab prenylation in vitro. Analysis of the effects of
      thermoreversible temperature-sensitive (mrs6(ts)) mutants on vesicular traffic in
      vivo showed prenylation activity is only transiently required to maintain normal
      growth, a result promising for therapeutic approaches to disease.

PMID- 10893260
TI  - Close is not enough: SNARE-dependent membrane fusion requires an active mechanism
      that transduces force to membrane anchors.
AB  - Is membrane fusion an essentially passive or an active process? It could be that
      fusion proteins simply need to pin two bilayers together long enough, and the
      bilayers could do the rest spontaneously. Or, it could be that the fusion
      proteins play an active role after pinning two bilayers, exerting force in the
      bilayer in one or another way to direct the fusion process. To distinguish these
      alternatives, we replaced one or both of the peptidic membrane anchors of
      exocytic vesicle (v)- and target membrane (t)-SNAREs (soluble N-ethylmaleimide
      sensitive fusion protein [NSF] attachment protein [SNAP] receptor) with
      covalently attached lipids. Replacing either anchor with a phospholipid prevented
      fusion of liposomes by the isolated SNAREs, but still allowed assembly of trans
      SNARE complexes docking vesicles. This result implies an active mechanism; if
      fusion occurred passively, simply holding the bilayers together long enough would
      have been sufficient. Studies using polyisoprenoid anchors ranging from 15-55
      carbons and multiple phospholipid-containing anchors reveal distinct requirements
      for anchors of v- and t-SNAREs to function: v-SNAREs require anchors capable of
      spanning both leaflets, whereas t-SNAREs do not, so long as the anchor is
      sufficiently hydrophobic. These data, together with previous results showing
      fusion is inhibited as the length of the linker connecting the helical bundle
      containing rod of the SNARE complex to the anchors is increased (McNew, J.A., T.
      Weber, D.M. Engelman, T.H. Sollner, and J.E. Rothman, 1999. Mol. Cell. 4:415
      421), suggests a model in which one activity of the SNARE complex promoting
      fusion is to exert force on the anchors by pulling on the linkers. This motion
      would lead to the simultaneous inward movement of lipids from both bilayers, and
      in the case of the v-SNARE, from both leaflets.

PMID- 10893261
TI  - The regulatory complex of Drosophila melanogaster 26S proteasomes. Subunit
      composition and localization of a deubiquitylating enzyme.
AB  - Drosophila melanogaster embryos are a source for homogeneous and stable 26S
      proteasomes suitable for structural studies. For biochemical characterization,
      purified 26S proteasomes were resolved by two-dimensional (2D) gel
      electrophoresis and subunits composing the regulatory complex (RC) were
      identified by amino acid sequencing and immunoblotting, before corresponding
      cDNAs were sequenced. 17 subunits from Drosophila RCs were found to have
      homologues in the yeast and human RCs. An additional subunit, p37A, not yet
      described in RCs of other organisms, is a member of the ubiquitin COOH-terminal
      hydrolase family (UCH). Analysis of EM images of 26S proteasomes-UCH-inhibitor
      complexes allowed for the first time to localize one of the RC's specific
      functions, deubiquitylating activity. The masses of 26S proteasomes with either
      one or two attached RCs were determined by scanning transmission EM (STEM),
      yielding a mass of 894 kD for a single RC. This value is in good agreement with
      the summed masses of the 18 identified RC subunits (932 kD), indicating that the
      number of subunits is complete.

PMID- 10893262
TI  - Caspase inhibition extends the commitment to neuronal death beyond cytochrome c
      release to the point of mitochondrial depolarization.
AB  - Nerve growth factor (NGF) deprivation induces a Bax-dependent, caspase-dependent
      programmed cell death in sympathetic neurons. We examined whether the release of
      cytochrome c was accompanied by the loss of mitochondrial membrane potential
      during sympathetic neuronal death. NGF- deprived, caspase inhibitor-treated mouse
      sympathetic neurons maintained mitochondrial membrane potential for 25-30 h after
      releasing cytochrome c. NGF- deprived sympathetic neurons became committed to
      die, as measured by the inability of cells to be rescued by NGF readdition, at
      the time of cytochrome c release. In the presence of caspase inhibitor, however,
      this commitment to death was extended beyond the point of cytochrome c release,
      but only up to the subsequent point of mitochondrial membrane potential loss.
      Caspase-9 deficiency also arrested NGF-deprived sympathetic neurons after release
      of cytochrome c, and permitted these neurons to be rescued with NGF readdition.
      Commitment to death in the NGF-deprived, caspase- 9-deficient sympathetic neurons
      was also coincident with the loss of mitochondrial membrane potential. Thus,
      caspase inhibition extended commitment to death in trophic factor-deprived
      sympathetic neurons and allowed recovery of neurons arrested after the loss of
      cytochrome c, but not beyond the subsequent loss of mitochondrial membrane
      potential.

PMID- 10893263
TI  - Evidence that dynamin-2 functions as a signal-transducing GTPase.
AB  - The role of dynamin GTPases in the regulation of receptor-mediated endocytosis is
      well established. Here, we present new evidence that the ubiquitously expressed
      isoform dynamin-2 (dyn2) can also function in a signal transduction pathway(s). A
      </=5-fold increase of dyn2 relative to endogenous levels activates the
      transcription factor p53 and induces apoptosis, as demonstrated by reduced cell
      proliferation, DNA fragmentation, and caspase-3 activation. Dyn2-triggered
      apoptosis occurs only in dividing cells and is p53 dependent. A mutant defective
      in GTP binding does not trigger apoptosis, indicating that increased levels of
      dyn2.GTP, rather than protein levels per se, are required to transduce signals
      that activate p53. A truncated dyn2 lacking the COOH-terminal proline/arginine
      rich domain (PRD), which interacts with many SH3 domain-containing partners
      implicated in both endocytosis and signal transduction, triggers apoptosis even
      more potently than the wild-type. This observation provides additional support
      for the importance of the NH(2)-terminal GTPase domain for the apoptotic
      phenotype. All described effects are dyn2-specific because >200-fold
      overexpression of dyn1, the 70% identical neuronal isoform, has no effect. Our
      data suggest that dyn2 can act as a signal transducing GTPase affecting
      transcriptional regulation.

PMID- 10893264
TI  - Sphingomyelin hydrolysis to ceramide during the execution phase of apoptosis
      results from phospholipid scrambling and alters cell-surface morphology.
AB  - Apoptosis is generally accompanied by a late phase of ceramide (Cer) production,
      the significance of which is unknown. This study describes a previously
      unrecognized link between Cer accumulation and phosphatidylserine (PS) exposure
      at the cell surface, a characteristic of the execution phase of apoptosis
      resulting from a loss of plasma membrane phospholipid asymmetry. Using a
      fluorescent sphingomyelin (SM) analogue, N-(N-[6-[(7-nitrobenz-2-oxa-1, 3-diazol
      4-yl)amino]caproyl]-sphingosylphosphorylcholine (C(6)-NBD-SM), we show that Cer
      is derived from SM, initially located in the outer leaflet of the plasma
      membrane, which gains access to a cytosolic SMase by flipping to the inner
      leaflet in a process of lipid scrambling paralleling PS externalization. Lipid
      scrambling is both necessary and sufficient for SM conversion: Ca(2+) ionophore
      induces both PS exposure and SM hydrolysis, whereas scrambling-deficient Raji
      cells do not show PS exposure or Cer formation. Cer is not required for
      mitochondrial or nuclear apoptotic features since these are still observed in
      Raji cells. SM hydrolysis facilitates cholesterol efflux to methyl-beta
      cyclodextrin, which is indicative of a loss of tight SM-cholesterol interaction
      in the plasma membrane. We provide evidence that these biophysical alterations in
      the lipid bilayer are essential for apoptotic membrane blebbing/vesiculation at
      the cell surface: Raji cells show aberrant apoptotic morphology, whereas
      replenishment of hydrolyzed SM by C(6)- NBD-SM inhibits blebbing in Jurkat cells.
      Thus, SM hydrolysis, during the execution phase of apoptosis, results from a loss
      of phospholipid asymmetry and contributes to structural changes at the plasma
      membrane.

PMID- 10893265
TI  - Glutamate slows axonal transport of neurofilaments in transfected neurons.
AB  - Neurofilaments are transported through axons by slow axonal transport. Abnormal
      accumulations of neurofilaments are seen in several neurodegenerative diseases,
      and this suggests that neurofilament transport is defective. Excitotoxic
      mechanisms involving glutamate are believed to be part of the pathogenic process
      in some neurodegenerative diseases, but there is currently little evidence to
      link glutamate with neurofilament transport. We have used a novel technique
      involving transfection of the green fluorescent protein-tagged neurofilament
      middle chain to measure neurofilament transport in cultured neurons. Treatment of
      the cells with glutamate induces a slowing of neurofilament transport.
      Phosphorylation of the side-arm domains of neurofilaments has been associated
      with a slowing of neurofilament transport, and we show that glutamate causes
      increased phosphorylation of these domains in cell bodies. We also show that
      glutamate activates members of the mitogen-activated protein kinase family, and
      that these kinases will phosphorylate neurofilament side-arm domains. These
      results provide a molecular framework to link glutamate excitotoxicity with
      neurofilament accumulation seen in some neurodegenerative diseases.

PMID- 10893266
TI  - Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor
      cell invasion and migration.
AB  - Tiam1 (T-lymphoma invasion and metastasis 1) is one of the known guanine
      nucleotide (GDP/GTP) exchange factors (GEFs) for Rho GTPases (e.g., Rac1) and is
      expressed in breast tumor cells (e.g., SP-1 cell line). Immunoprecipitation and
      immunoblot analyses indicate that Tiam1 and the cytoskeletal protein, ankyrin,
      are physically associated as a complex in vivo. In particular, the ankyrin repeat
      domain (ARD) of ankyrin is responsible for Tiam1 binding. Biochemical studies and
      deletion mutation analyses indicate that the 11-amino acid sequence between amino
      acids 717 and 727 of Tiam1 ((717)GEGTDAVKRS(727)L) is the ankyrin-binding domain.
      Most importantly, ankyrin binding to Tiam1 activates GDP/GTP exchange on Rho
      GTPases (e.g., Rac1). Using an Escherichia coli-derived calmodulin-binding
      peptide (CBP)-tagged recombinant Tiam1 (amino acids 393-728) fragment that
      contains the ankyrin-binding domain, we have detected a specific binding
      interaction between the Tiam1 (amino acids 393-738) fragment and ankyrin in
      vitro. This Tiam1 fragment also acts as a potent competitive inhibitor for Tiam1
      binding to ankyrin. Transfection of SP-1 cell with Tiam1 cDNAs stimulates all of
      the following: (1) Tiam1-ankyrin association in the membrane projection; (2) Rac1
      activation; and (3) breast tumor cell invasion and migration. Cotransfection of
      SP1 cells with green fluorescent protein (GFP)-tagged Tiam1 fragment cDNA and
      Tiam1 cDNA effectively blocks Tiam1-ankyrin colocalization in the cell membrane,
      and inhibits GDP/GTP exchange on Rac1 by ankyrin-associated Tiam1 and tumor
      specific phenotypes. These findings suggest that ankyrin-Tiam1 interaction plays
      a pivotal role in regulating Rac1 signaling and cytoskeleton function required
      for oncogenic signaling and metastatic breast tumor cell progression.

PMID- 10893267
TI  - Morphogenic effects of ezrin require a phosphorylation-induced transition from
      oligomers to monomers at the plasma membrane.
AB  - ERM (ezrin, radixin, moesin) proteins act as linkers between the plasma membrane
      and the actin cytoskeleton. An interaction between their NH(2)- and COOH-terminal
      domains occurs intramolecularly in closed monomers and intermolecularly in head
      to-tail oligomers. In vitro, phosphorylation of a conserved threonine residue
      (T567 in ezrin) in the COOH-terminal domain of ERM proteins disrupts this
      interaction. Here, we have analyzed the role of this phosphorylation event in
      vivo, by deriving stable clones producing wild-type, T567A, and T567D ezrin from
      LLC-PK1 epithelial cells. We found that T567A ezrin was poorly associated with
      the cytoskeleton, but was able to form oligomers. In contrast, T567D ezrin was
      associated with the cytoskeleton, but its distribution was shifted from oligomers
      to monomers at the membrane. Moreover, production of T567D ezrin induced the
      formation of lamellipodia, membrane ruffles, and tufts of microvilli. Both T567A
      and T567D ezrin affected the development of multicellular epithelial structures.
      Collectively, these results suggest that phosphorylation of ERM proteins on this
      conserved threonine regulates the transition from membrane-bound oligomers to
      active monomers, which induce and are part of actin-rich membrane projections.

PMID- 10893268
TI  - Agrin-induced acetylcholine receptor clustering is mediated by the small
      guanosine triphosphatases Rac and Cdc42.
AB  - During neuromuscular junction formation, agrin secreted from motor neurons causes
      muscle cell surface acetylcholine receptors (AChRs) to cluster at synaptic sites
      by mechanisms that are insufficiently understood. The Rho family of small
      guanosine triphosphatases (GTPases), including Rac and Cdc42, can mediate focal
      reorganization of the cell periphery in response to extracellular signals. Here,
      we investigated the role of Rac and Cdc42 in coupling agrin signaling to AChR
      clustering. We found that agrin causes marked muscle-specific activation of Rac
      and Cdc42 in differentiated myotubes, as detected by biochemical measurements.
      Moreover, this activation is crucial for AChR clustering, since the expression of
      dominant interfering mutants of either Rac or Cdc42 in myotubes blocks agrin
      induced AChR clustering. In contrast, constitutively active Rac and Cdc42 mutants
      cause AChR to aggregate in the absence of agrin. By indicating that agrin
      dependent activation of Rac and Cdc42 constitutes a critical step in the
      signaling pathway leading to AChR clustering, these findings suggest a novel role
      for these Rho-GTPases: the coupling of neuronal signaling to a key step in
      neuromuscular synaptogenesis.

PMID- 10893269
TI  - Intracellular pH regulation by Na(+)/H(+) exchange requires phosphatidylinositol
      4,5-bisphosphate.
AB  - The carrier-mediated, electroneutral exchange of Na(+) for H(+) across the plasma
      membrane does not directly consume metabolic energy. Nevertheless, acute
      depletion of cellular ATP markedly decreases transport. We analyzed the possible
      involvement of polyphosphoinositides in the metabolic regulation of NHE1, the
      ubiquitous isoform of the Na(+)/H(+) exchanger. Depletion of ATP was accompanied
      by a marked reduction of plasmalemmal phosphatidylinositol 4,5-bisphosphate
      (PIP(2)) content. Moreover, sequestration or hydrolysis of plasmalemmal PIP(2),
      in the absence of ATP depletion, was associated with profound inhibition of NHE1
      activity. Examination of the primary structure of the COOH-terminal domain of
      NHE1 revealed two potential PIP(2)-binding motifs. Fusion proteins encoding these
      motifs bound PIP(2) in vitro. When transfected into antiport-deficient cells,
      mutant forms of NHE1 lacking the putative PIP(2)-binding domains had greatly
      reduced transport capability, implying that association with PIP(2) is required
      for optimal activity. These findings suggest that NHE1 activity is modulated by
      phosphoinositides and that the inhibitory effect of ATP depletion may be
      attributable, at least in part, to the accompanying net dephosphorylation of
      PIP(2).

PMID- 10893270
TI  - Wnt/frizzled-2 signaling induces aggregation and adhesion among cardiac myocytes
      by increased cadherin-beta-catenin complex.
AB  - Wingless is known to be required for induction of cardiac mesoderm in Drosophila,
      but the function of Wnt family proteins, vertebrate homologues of wingless, in
      cardiac myocytes remains unknown. When medium conditioned by HEK293 cells
      overexpressing Wnt-3a or -5a was applied to cultured neonatal cardiac myocytes,
      Wnt proteins induced myocyte aggregation in the presence of fibroblasts,
      concomitant with increases in beta-catenin and N-cadherin in the myocytes and
      with E- and M-cadherins in the fibroblasts. The aggregation was inhibited by anti
      N-cadherin antibody and induced by constitutively active beta-catenin, but was
      unaffected by dominant negative and dominant positive T cell factor (TCF)
      mutants. Thus, increased stabilization of complexed cadherin-beta-catenin in both
      cell types appears crucial for the morphological effect of Wnt on cardiac
      myocytes. Furthermore, myocytes overexpressing a dominant negative frizzled-2,
      but not a dominant negative frizzled-4, failed to aggregate in response to Wnt,
      indicating frizzled-2 to be the predominant receptor mediating aggregation. By
      contrast, analysis of bromodeoxyuridine incorporation and transcription of
      various cardiogenetic markers showed Wnt to have little or no impact on cell
      proliferation or differentiation. These findings suggest that a Wnt-frizzled-2
      signaling pathway is centrally involved in the morphological arrangement of
      cardiac myocytes in neonatal heart through stabilization of complexed cadherin-
      beta-catenin.

PMID- 10893271
TI  - Intercellular adhesion molecule-5 induces dendritic outgrowth by homophilic
      adhesion.
AB  - Intercellular adhesion molecule-5 (ICAM-5) is a dendritically polarized membrane
      glycoprotein in telencephalic neurons, which shows heterophilic binding to
      leukocyte beta(2)-integrins. Here, we show that the human ICAM-5 protein
      interacts in a homophilic manner through the binding of the immunoglobulin domain
      1 to domains 4-5. Surface coated ICAM-5-Fc promoted dendritic outgrowth and
      arborization of ICAM- 5-expressing hippocampal neurons. During dendritogenesis in
      developing rat brain, ICAM-5 was in monomer form, whereas in mature neurons it
      migrated as a high molecular weight complex. The findings indicate that its
      homophilic binding activity was regulated by nonmonomer/monomer transition. Thus,
      ICAM-5 displays two types of adhesion activity, homophilic binding between
      neurons and heterophilic binding between neurons and leukocytes.

PMID- 10893272
TI  - The UNC-112 gene in Caenorhabditis elegans encodes a novel component of cell
      matrix adhesion structures required for integrin localization in the muscle cell
      membrane.
AB  - Embryos homozygous for mutations in the unc-52, pat-2, pat-3, and unc-112 genes
      of C. elegans exhibit a similar Pat phenotype. Myosin and actin are not organized
      into sarcomeres in the body wall muscle cells of these mutants, and dense body
      and M-line components fail to assemble. The unc-52 (perlecan), pat-2 (alpha
      integrin), and pat-3 (beta-integrin) genes encode ECM or transmembrane proteins
      found at the cell-matrix adhesion sites of both dense bodies and M-lines. This
      study describes the identification of the unc-112 gene product, a novel, membrane
      associated, intracellular protein that colocalizes with integrin at cell-matrix
      adhesion complexes. The 720-amino acid UNC-112 protein is homologous to Mig-2, a
      human protein of unknown function. These two proteins share a region of homology
      with talin and members of the FERM superfamily of proteins. We have determined
      that a functional UNC-112::GFP fusion protein colocalizes with PAT-3/beta
      integrin in both adult and embryonic body wall muscle. We also have determined
      that UNC-112 is required to organize PAT-3/beta-integrin after it is integrated
      into the basal cell membrane, but is not required to organize UNC-52/perlecan in
      the basement membrane, nor for DEB-1/vinculin to localize with PAT-3/beta
      integrin. Furthermore, UNC-112 requires the presence of UNC-52/perlecan and PAT
      3/beta-integrin, but not DEB-1/vinculin to become localized to the muscle cell
      membrane.

PMID- 10893273
TI  - CREB-binding protein (CBP)/p300 and RNA polymerase II colocalize in
      transcriptionally active domains in the nucleus.
AB  - The spatial organization of transcription- associated proteins is an important
      control mechanism of eukaryotic gene expression. Here we analyzed the nuclear
      distribution of the transcriptional coactivators CREB-binding protein (CBP)/p300
      in situ by confocal laser scanning microscopy, and in vivo complex formation by
      coimmunoprecipitation. A subpopulation of CBP and p300 is targeted to active
      sites of transcription and partially colocalizes with hyper- and
      hypophosphorylated RNA polymerase II (pol II) in discrete regions of variable
      size throughout the nucleus. However, the coactivators were found in tight
      association with hypophosphorylated, but not hyperphosphorylated pol II.
      Transcriptional inhibition induced a relocation of CBP/p300 and pol II into
      speckles. Moreover, double and triple immunofluorescence analyses revealed the
      presence of CBP, p300, and pol II in a subset of promyelocytic leukemia (PML)
      bodies. Our results provide evidence for a dynamic spacial link between
      coactivators of transcription and the basal transcription machinery in discrete
      nuclear domains dependent upon the transcriptional activity of the cell. The
      identification of pol II in CBP/PML-containing nuclear bodies supports the idea
      that transcription takes place at PML bodies.

PMID- 10893274
TI  - Fibroblast growth factor 2 internal ribosome entry site (IRES) activity ex vivo
      and in transgenic mice reveals a stringent tissue-specific regulation.
AB  - Fibroblast growth factor 2 (FGF-2) is a powerful mitogen involved in
      proliferation, differentiation, and survival of various cells including neurons.
      FGF-2 expression is translationally regulated; in particular, the FGF-2 mRNA
      contains an internal ribosome entry site (IRES) allowing cap-independent
      translation. Here, we have analyzed FGF-2 IRES tissue specificity ex vivo and in
      vivo by using a dual luciferase bicistronic vector. This IRES was active in most
      transiently transfected human and nonhuman cell types, with a higher activity in
      p53 -/- osteosarcoma and neuroblastoma cell lines. Transgenic mice were generated
      using bicistronic transgenes with FGF-2 IRES or encephalomyocarditis virus (EMCV)
      IRES. Measurements of luciferase activity revealed high FGF-2 IRES activity in 11
      d-old embryos (E11) but not in the placenta; activity was high in the heart and
      brain of E16. FGF-2 IRES activity was low in most organs of the adult, but
      exceptionally high in the brain. Such spatiotemporal variations were not observed
      with the EMCV IRES. These data, demonstrating the strong tissue specificity of a
      mammalian IRES in vivo, suggest a pivotal role of translational IRES- dependent
      activation of FGF-2 expression during embryogenesis and in adult brain. FGF-2
      IRES could constitute, thus, a powerful tool for gene transfer in the central
      nervous system.

PMID- 10893275
TI  - Seeking common ground in nuclear complexity.

PMID- 10893276
TI  - Apoptosis and sphingomyelin hydrolysis. The flip side.

PMID- 10893277
TI  - UNC112. A new regulator of cell-extracellular matrix adhesions?

PMID- 10893279
TI  - Discussing complementary therapies with cancer patients: what should we be
      talking about?

PMID- 10893280
TI  - Complementary/alternative medicine use in a comprehensive cancer center and the
      implications for oncology.
AB  - PURPOSE: Oncologists are aware that their patients use complementary/alternative
      medicine (CAM). As cancer incidence rates and survival time increase, use of CAM
      will likely increase. This study assessed the prevalence and predictors of CAM
      use in a comprehensive cancer center. SUBJECTS AND METHODS: Subjects were English
      speaking cancer patients at least 18 years of age, attending one of eight
      outpatient clinics at The University of Texas M.D. Anderson Cancer Center,
      Houston, TX, between December 1997 and June 1998. After giving written informed
      consent, participants completed a self-administered questionnaire. Differences
      between CAM users and nonusers were assessed by chi(2) and univariate logistic
      regression analysis. A multivariate logistic regression model identified the
      simultaneous impact of demographic, clinical, and treatment variables on CAM use;
      P values were two-sided. RESULTS: Of the 453 participants (response rate, 51.4%),
      99.3% had heard of CAM. Of those, 83.3% had used at least one CAM approach. Use
      was greatest for spiritual practices (80.5%), vitamins and herbs (62.6%), and
      movement and physical therapies (59.2%) and predicted (P <.001) by sex (female),
      younger age, indigent pay status, and surgery. After excluding spiritual
      practices and psychotherapy, 95.8% of participants were aware of CAM and 68.7% of
      those had used CAM. Use was predicted (P <.0001) by sex (female), education, and
      chemotherapy. CONCLUSION: In most categories, CAM use was common among
      outpatients. Given the number of patients combining vitamins and herbs with
      conventional treatments, the oncology community must improve patient-provider
      communication, offer reliable information to patients, and initiate research to
      determine possible drug-herb-vitamin interactions.

PMID- 10893281
TI  - Use of complementary/alternative medicine by breast cancer survivors in Ontario:
      prevalence and perceptions.
AB  - PURPOSE: To determine the prevalence of use of complementary/alternative medicine
      (CAM) by breast cancer survivors in Ontario, Canada, and to compare the
      characteristics of CAM users and CAM nonusers. PATIENTS AND METHODS: A
      questionnaire was mailed to a random sample of Ontario women diagnosed with
      breast cancer in 1994 or 1995. RESULTS: The response rate was 76.3%. Overall,
      66.7% of the respondents reported using CAM, most often in an attempt to boost
      the immune system. CAM practitioners (most commonly chiropractors, herbalists,
      acupuncturists, traditional Chinese medicine practitioners, and/or naturopathic
      practitioners) were visited by 39.4% of the respondents. In addition, 62.0%
      reported use of CAM products (most frequently vitamins/minerals, herbal
      medicines, green tea, special foods, and essiac). Almost one half of the
      respondents informed their physicians of their use of CAM. Multiple logistic
      regression analysis determined that support group attendance was the only factor
      significantly associated with CAM use. CONCLUSION: CAM use is common among
      Canadian breast cancer survivors, many of whom are discussing CAM therapy options
      with their physicians. Knowledge of CAM therapies is necessary for physicians and
      other health care practitioners to help patients make informed choices. CAM use
      may play a role in the positive benefits associated with support group
      attendance.

PMID- 10893282
TI  - Randomized, dose-escalation study of SD/01 compared with daily filgrastim in
      patients receiving chemotherapy.
AB  - PURPOSE: To explore the use of SD/01 (a polyethylene glycol-conjugated filgrastim
      shown in preclinical studies to have a prolonged half-life) in patients with
      chemotherapy-induced neutropenia. PATIENTS AND METHODS: Thirteen patients with
      non-small-cell lung cancer were randomized to receive daily filgrastim (5
      microg/kg/d) or a single injection of SD/01 (30, 100, or 300 microg/kg) 2 weeks
      before chemotherapy and again 24 hours after administration of carboplatin and
      paclitaxel. Pharmacodynamic, pharmacokinetic, and safety analyses were performed.
      RESULTS: Peak serum concentrations of SD/01 and the duration of increased serum
      concentrations were dependent on the SD/01 dose. SD/01 concentrations remained
      increased longer in patients with chemotherapy-induced neutropenia.
      Prechemotherapy median absolute neutrophil counts (ANCs) in patients receiving
      SD/01 were increased in a dose-dependent fashion, with the duration of this
      effect also being dose dependent. After chemotherapy, median ANC nadirs were
      similar in the filgrastim cohort and the cohort receiving SD/01 30 microg/kg,
      with higher nadirs seen in the cohorts receiving SD/01 100 or 300 microg/kg. Dose
      limiting toxicities were not noted. CD34(+) cells were mobilized in all cohorts.
      CONCLUSION: A single dose of SD/01 increases the serum concentration of SD/01 for
      several days in a dose-dependent fashion and is not associated with significant
      toxicity. The effects of SD/01 on ANC and CD34(+) cell mobilization are
      comparable or greater than those achieved with daily filgrastim. The self
      regulation of this molecule provides a potential therapeutic advantage in a
      variety of clinical settings associated with neutropenia.

PMID- 10893283
TI  - Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with
      advanced non-small-cell lung cancer.
AB  - PURPOSE: To evaluate whether the addition of gemcitabine (G) to vinorelbine (V)
      improves survival and quality of life (QoL) among elderly patients with advanced
      non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with NSCLC
      aged >/= 70 years with advanced disease were randomly allocated to receive V 30
      mg/m(2) on days 1 and 8 every 3 weeks or G 1,200 mg/m(2) + V 30 mg/m(2) on days 1
      and 8 every 3 weeks. The estimated sample size was 120 patients per arm, but an
      interim analysis of survival was planned based on the first 60 patients per arm.
      RESULTS: In May 1999, the survival data were analyzed of 120 eligible patients (V
      group = 60; G + V group = 60) who had been randomized from June 1997 to February
      1999. Forty-nine patients had stage IIIB disease, and 71 had stage IV. At a
      median potential follow-up of 14 months (range, 3 to 22 months), 93 patients had
      died (G + V group = 41; V group = 52). In the G + V group, median survival time
      was 29 weeks and projected 1-year survival was 30%; these values were 18 weeks
      and 13% in the V group. According to multivariate Cox analysis, the risk of death
      in the G + V arm compared with the V arm was 0.48 (95% confidence interval, 0. 29
      to 0.79; P <.01). Combination therapy was also associated with a clear delay in
      symptom and QoL deterioration. The overall response rates were 22% and 15% in the
      G + V and V groups, respectively. CONCLUSION: In elderly patients with NSCLC, G +
      V treatment is associated with significantly better survival than is V alone.

PMID- 10893284
TI  - Southwest Oncology Group Study of paclitaxel and carboplatin for advanced
      transitional-cell carcinoma: the importance of survival as a clinical trial end
      point.
AB  - PURPOSE: The combination of paclitaxel and carboplatin for the treatment of
      advanced transitional-cell carcinoma (TCC) of the urothelium has promising
      activity and acceptable toxicity. The purpose of this trial was to evaluate the
      efficacy of this regimen in a cooperative group setting. PATIENTS AND METHODS:
      Twenty-nine patients with advanced TCC were treated every 21 days with paclitaxel
      200 mg/m(2), administered as a 3-hour infusion, followed by carboplatin dosed to
      an area under the curve of 5. Prior systemic adjuvant or neoadjuvant platinum
      based therapy was not permitted unless completed at least 1 year before
      enrollment. Patients were evaluated for response every three cycles, and follow
      up was conducted to determine survival. RESULTS: Twenty-nine patients were
      enrolled and were assessable. Four (14%) had received prior adjuvant or
      neoadjuvant therapy. Node-only disease was present in 24%, and 76% of patients
      had extranodal disease. The median number of cycles received was five. Grade 4
      toxicity consisted primarily of neutropenia (38% of patients). Neurologic
      toxicity was noted in 16 patients (grade 1 in four patients, grade 2 in five
      patients, grade 3 in six patients, and grade 4 in one patient). Six partial
      responses and no complete responses were noted, for a response proportion of
      20.7% (95% confidence interval, 8% to 40%). Median progression-free survival time
      was 4 months, and overall survival time was 9 months. CONCLUSION: The combination
      of paclitaxel and carboplatin for the treatment of advanced TCC is reasonably
      well tolerated. However, a response proportion considerably lower than that
      previously reported was noted. In addition, the median survival time of 9 months
      was less than the survival time previously reported for patients treated with the
      combination of methotrexate, vinblastine, doxorubicin, and cisplatin. Although
      our results may reflect enrollment of patients with poor prognostic features,
      they also call into question the utility of this regimen.

PMID- 10893285
TI  - Gemcitabine in combination with doxorubicin in advanced breast cancer: final
      results of a phase II pharmacokinetic trial.
AB  - PURPOSE: Gemcitabine has promising single-agent activity in advanced breast
      disease. The aim of this phase II study was to determine the efficacy, toxicity,
      and pharmacokinetic profile of gemcitabine administered with doxorubicin as first
      line treatment in patients with metastatic breast cancer. PATIENTS AND METHODS:
      Of the 42 women with metastatic breast cancer (age 33 to 74 years; mean age, 55
      years), 13 were chemotherapy-naive and 29 had received adjuvant chemotherapy.
      Gemcitabine (800 or 1,000 mg/m(2)) and doxorubicin (25 mg/m(2)) were administered
      intravenously on days 1, 8, and 15 of each 28-day cycle. Blood samples were drawn
      on day 8 of cycles 1, 2, and 3 and of subsequent odd cycles for gemcitabine
      pharmacokinetic determinations and before and after the first dose of cycle 1 or
      2 for doxorubicin determinations. RESULTS: There were three complete and 20
      partial responses, for an overall response rate of 55% (95% confidence interval
      [CI], 40% to 70%) and a complete response rate of 7%. The median survival time
      for all 42 patients was 27 months (95% CI, 13.4 to 30.0 months) and the 1-year
      survival rate was 80%. Toxicity was mainly hematologic. The disposition of both
      drugs was unchanged when they were administered on the same day compared with
      when they were given singly. CONCLUSION: The combination of gemcitabine (800
      mg/m(2)) and doxorubicin (25 mg/m(2)) can be safely administered using a weekly
      schedule. The disposition of both drugs is unchanged when they are administered
      on the same day. This combination shows promising activity with acceptable
      toxicity compared with other combination therapies.

PMID- 10893286
TI  - Prospective observational study of sentinel lymphadenectomy without further
      axillary dissection in patients with sentinel node-negative breast cancer.
AB  - PURPOSE: Immediate complete axillary lymphadenectomy (ALND) after sentinel
      lymphadenectomy (SLND) has confirmed that tumor-negative sentinel nodes
      accurately predict tumor-free axillary nodes in breast cancer. Therefore, we
      hypothesized that SLND alone in patients with tumor-negative sentinel nodes would
      achieve axillary control, with minimal complications. PATIENTS AND METHODS:
      Between October 1995 and July 1997, 133 consecutive women who had primary
      invasive breast tumors clinically </= 4 cm in diameter and no axillary
      lymphadenopathy were prospectively entered onto a trial of SLND using vital blue
      dye. Sentinel nodes were examined by standard microscopy or immunohistochemistry.
      SLND was the only axillary surgery if sentinel nodes were tumor-free. Completion
      ALND was performed only if sentinel nodes contained metastases or if they were
      not identified. Excluded from subsequent analysis were patients with unsuspected
      multifocal carcinoma and those who refused completion ALND. The complication and
      axillary recurrence rates after SLND without ALND were determined. RESULTS:
      Sentinel nodes were identified in 132 (99%) of 133 patients. Eight patients were
      excluded from further analysis. Of the 125 assessable patients, 57 had tumor
      positive sentinel nodes and one had an unsuccessful mapping procedure; these
      patients underwent completion ALND. In the remaining 67 patients (54%), SLND was
      the only axillary procedure. Complications occurred in 20 patients (35%)
      undergoing ALND after SLND but in only two patients (3%) undergoing SLND alone (P
      =.001). There were no local or axillary recurrences at a median follow-up of 39
      months. CONCLUSION: Complication rates are negligible after SLND alone. An
      absence of axillary recurrences supports SLND as an accurate staging alternative
      for breast cancer and suggests that routine ALND can be eliminated for patients
      with histopathologically negative sentinel nodes.

PMID- 10893287
TI  - Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine
      axillary dissection in multi-institutional practice when optimal technique is
      used.
AB  - PURPOSE: Previous studies have demonstrated the feasibility of sentinel lymph
      node (SLN) biopsy for nodal staging of patients with breast cancer. However,
      unacceptably high false-negative rates have been reported in several studies,
      raising doubt about the applicability of this technique in widespread surgical
      practice. Controversy persists regarding the optimal technique for correctly
      identifying the SLN. Some investigators advocate SLN biopsy using injection of a
      vital blue dye, others recommend radioactive colloid, and still others recommend
      the use of both agents together. PATIENTS AND METHODS: A total of 806 patients
      were enrolled by 99 surgeons. SLN biopsy was performed by single-agent (blue dye
      alone or radioactive colloid alone) or dual-agent injection at the discretion of
      the operating surgeon. All patients underwent attempted SLN biopsy followed by
      completion level I/II axillary lymph node dissection to determine the false
      negative rate. RESULTS: There was no significant difference (86% v 90%) in the
      SLN identification rate among patients who underwent single- versus dual-agent
      injection. The false-negative rates were 11.8% and 5.8% for single- versus dual
      agent injection, respectively (P <.05). Dual-agent injection resulted in a
      greater mean number of SLNs identified per patient (2. 1 v 1.5; P <.0001). The
      SLN identification rate was significantly less for patients older than 50 years
      as compared with that of younger patients (87.6% v 92.6%; P =.03). Upper-outer
      quadrant tumor location was associated with an increased likelihood of a false
      negative result compared with all other locations (11.2% v 3. 9%; P <.05).
      CONCLUSION: In multi-institutional practice, SLN biopsy using dual-agent
      injection provides optimal sensitivity for detection of nodal metastases. The
      acceptable SLN identification and false-negative rates associated with the dual
      agent injection technique indicate that this procedure is a suitable alternative
      to routine axillary dissection across a wide spectrum of surgical practice and
      hospital environments.

PMID- 10893288
TI  - Tandem high-dose therapy in rapid sequence for children with high-risk
      neuroblastoma.
AB  - PURPOSE: Advances in chemotherapy and supportive care have slowly improved
      survival rates for patients with high-risk neuroblastoma. The focus of many of
      these chemotherapeutic advances has been dose intensification. In this phase II
      trial involving children with advanced neuroblastoma, we used a program of
      induction chemotherapy followed by tandem high-dose, myeloablative treatments
      (high-dose therapy) with stem-cell rescue (HDT/SCR) in rapid sequence. PATIENTS
      AND METHODS: Patients underwent induction chemotherapy during which peripheral
      blood stem and progenitor cells were collected and local control measures
      undertaken. Patients then received tandem courses of HDT/SCR, 4 to 6 weeks apart.
      Thirty-nine patients (age 1 to 12 years) were assessable, and 70 cycles of
      HDT/SCR were completed. RESULTS: Pheresis was possible in the case of all
      patients, despite their young ages, with an average of 7.2 x 10(6) CD34(+)
      cells/kg available to support each cycle. Engraftment was rapid; median time to
      neutrophil engraftment was 11 days. Four patients who completed the first HDT
      course did not complete the second, and there were three deaths due to toxicity.
      With a median follow-up of 22 months (from diagnosis), 26 of 39 patients remained
      event-free. The 3-year event-free survival rate for these patients was 58%.
      CONCLUSION: A tandem HDT/SCR regimen for high-risk neuroblastoma is a feasible
      treatment strategy for children and may improve disease-free survival.

PMID- 10893289
TI  - Fractionated cyclophosphamide and etoposide for children with advanced or
      refractory solid tumors: a phase II window study.
AB  - PURPOSE: Cyclophosphamide (CPA) has a broad spectrum of activity against solid
      tumors. Hepatic self-induction of the active metabolite 4-hydroxycyclophosphamide
      occurs after repeated administration. We evaluated the clinical efficacy of a
      window regimen that administers fractionated CPA in conjunction with etoposide
      (VP16) in children with advanced or refractory solid tumors. PATIENTS AND
      METHODS: Seventeen children with advanced (n = 12) or refractory (n = 5) solid
      tumors were entered onto this phase II window study. The treatment regimen
      consisted of intravenous (IV) CPA 500 mg/m(2)/d and IV VP16 100 mg/m(2)/d. Both
      drugs were administered daily by short infusions for 5 consecutive days. RESULTS:
      A total of 34 courses were administered, with a median of two courses per
      patient. The median interval between chemotherapy courses was 21 days (range, 17
      to 35 days). Thirty-three courses were assessable for toxicity, and all patients
      were assessable for response. No life-threatening toxicities were observed. The
      incidence of grade 3 or 4 neutropenia was 94% and of fever and neutropenia 38%.
      Fever and neutropenia occurred after 12 of 26 courses without recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) and after one of eight courses
      with rhG-CSF (P =. 09). Grade 3 or 4 thrombocytopenia occurred after 10 courses
      (29%). There were no positive blood cultures. One heavily pretreated patient
      developed a localized perirectal abscess that required drainage. There were 10
      patients (59%) with partial responses, four (23.5%) with stable disease, and
      three with progressive disease. CONCLUSION: Fractionated IV CPA and VP16 over 5
      days can be safely administered in children with advanced or refractory solid
      tumors and has notable antineoplastic activity.

PMID- 10893290
TI  - Telomerase activity and telomerase subunits gene expression patterns in
      neuroblastoma: a molecular and immunohistochemical study establishing prognostic
      tools for fresh-frozen and paraffin-embedded tissues.
AB  - PURPOSE: We have recently demonstrated that telomerase activity (TA) is an
      independent prognostic factor in neuroblastomas. In the present study, the
      prognostic impact of TA and gene expression of the three major telomerase
      subunits is evaluated by molecular and immunohistochemical techniques in fresh
      frozen and paraffin-embedded tissues. PATIENTS AND METHODS: One hundred thirty
      three neuroblastomas of all stages were analyzed for TA. The TA levels of 75
      neuroblastoma cases were correlated with gene expression of telomerase subunits
      hTRT, human telomerase RNA (hTR), and telomerase protein 1 (TP1) by quantitative
      reverse transcriptase polymerase chain reaction (RT-PCR), using an innovative
      approach on the LightCycler instrument (Roche Diagnostics, Mannheim, Germany).
      For selected cases, the applicability of RT-PCR and immunohistochemistry for hTRT
      expression analysis was investigated in paraffin-embedded tissues. TA and subunit
      expression patterns were correlated with traditional prognostic indicators and
      disease outcome. RESULTS: TA was present in a total of 39 (29.3%) of 133
      neuroblastomas and in 31 (29.8%) of 104 initial neuroblastomas without cytotoxic
      pretreatment. TA was significantly correlated with both event-free and overall
      survival (P <.0001). Furthermore, we found a significant correlation between
      expression levels of TA and hTRT (P <.0001) as well as hTR (P <.001).
      Multivariate analysis revealed only TA and tumor stage but not serum lactate
      dehydrogenase, MYCN amplification, or age at diagnosis as independent prognostic
      factors. CONCLUSION: The significant correlation with clinical outcome strongly
      recommends that analysis of TA be incorporated into the clinical investigation of
      each individual neuroblastoma at the time of diagnosis. Because the mere presence
      or absence of TA without further quantification is sufficient basis for
      predicting disease outcome, the telomeric repeat amplification protocol assay
      could be complemented with but not replaced by analysis of hTRT or hTR
      expression.

PMID- 10893291
TI  - Activity of thalidomide in AIDS-related Kaposi's sarcoma.
AB  - PURPOSE: To assess the toxicity and activity of oral thalidomide in Kaposi's
      sarcoma (KS) in a phase II dose-escalation study. PATIENTS AND METHODS: Human
      immunodeficiency virus (HIV)-seropositive patients with biopsy-confirmed KS that
      progressed over the 2 months before enrollment received an initial dose of 200
      mg/d of oral thalidomide in a phase II study. The dose was increased to a maximum
      of 1,000 mg/d for up to 1 year. Anti-HIV therapy was maintained during the study
      period. Toxicity, tumor response, immunologic and angiogenic factors, and
      virologic parameters were assessed. RESULTS: Twenty patients aged 29 to 49 years
      with a median CD4 count of 246 cells/mm(3) (range, 14 to 646 cells/mm(3)) were
      enrolled. All patients were assessable for toxicity, and 17 for response.
      Drowsiness in nine and depression in seven patients were the most frequent
      toxicities observed. Eight (47%; 95% confidence interval [CI], 23% to 72%) of the
      17 assessable patients achieved a partial response, and an additional two
      patients had stable disease. Based on all 20 patients treated, the response rate
      was 40% (95% CI, 19% to 64%). The median thalidomide dose at the time of response
      was 500 mg/d (range, 400 to 1,000 mg/d). The median duration of drug treatment
      was 6.3 months, and the median time to progression was 7.3 months. CONCLUSION:
      Oral thalidomide was tolerated in this population at doses up to 1,000 mg/d for
      as long as 12 months and was found to induce clinically meaningful anti-KS
      responses in a sizable subset of the patients. Additional studies of this agent
      in KS are warranted.

PMID- 10893292
TI  - Gemcitabine treatment in pretreated cutaneous T-cell lymphoma: experience in 44
      patients.
AB  - PURPOSE: To evaluate the efficacy and toxicity of gemcitabine, a novel pyrimidine
      antimetabolite with a low-toxicity profile and activity in several solid tumors,
      in patients with relapsed or refractory cutaneous T-cell lymphomas. PATIENTS AND
      METHODS: Between May 1997 and February 1999, 44 previously treated patients with
      mycosis fungoides (MF; n = 30) and peripheral T-cell lymphoma unspecified (PTCLU)
      with exclusive skin involvement (n = 14) were enrolled onto a two-institution,
      phase II trial and treated with gemcitabine. This drug was given on days 1, 8,
      and 15 of a 28-day schedule at a dose of 1,200 mg/m(2) intravenously over 30
      minutes for a total of three courses. RESULTS: Of the 44 patients, five (11. 5%)
      achieved complete responses (CRs), 26 (59%) partial responses (PRs), and the
      remaining 13 showed no benefit from the treatment. Two of the CRs were
      histologically confirmed. The CR and PR rates were the same for patients with MF
      and those with PTCLU, respectively. No difference in terms of overall response
      rate was observed between relapsed and refractory patients. The median durations
      of CR and PR were 15 months (range, 6 to 22 months) and 10 months (range, 2 to 15
      months), respectively. Treatment was well tolerated; hematologic toxicity was
      mild, and no nausea/vomiting or organ toxicity was recorded. CONCLUSION: The
      results of the present phase II study show activity of gemcitabine as a single
      agent in patients with pretreated cutaneous T-cell lymphoma. Further studies that
      use gemcitabine alone or in combination with other drugs in earlier stages of the
      disease are needed.

PMID- 10893293
TI  - Acquired chromosome 11q deletion involving the ataxia teleangiectasia locus in B
      cell non-Hodgkin's lymphoma: correlation with clinicobiologic features.
AB  - PURPOSE: To study the clinicobiologic significance of acquired 11q deletions
      involving the ataxia teleangiectasia locus (ATM+/-) in B-cell non-Hodgkin's
      lymphomas (NHL). PATIENTS AND METHODS: Fifty-three indolent lymphomas and 82
      aggressive lymphomas were studied by conventional cytogenetic analysis and by
      fluorescence in situ hybridization using an 11q22-23 probe recognizing ATM
      sequences. Pertinent clinical data were collected. RESULTS: A hemizygous ATM
      deletion was seen in 44% to 88% of the interphase cells in 15 cases (11.1%); four
      patients had an indolent lymphoma (follicular center cell lymphoma), and 11
      patients had an aggressive lymphoma (five mantle-cell lymphomas [MCLs] and six
      diffuse large-cell lymphomas). Dual-color hybridization studies showed ATM
      deletion to be possibly a secondary aberration in three patients with MCL. Ten
      out of 15 ATM+/- patients had a complex karyotype, 11 out of 15 had more than 90%
      abnormal metaphases (AA karyotype status), and +12, 13q14 deletion, and 17p13
      deletion were seen in seven, four, and five cases, respectively. Patients with
      ATM+/- more frequently had a complex karyotype (P =.01) and the AA karyotype (P
      =.04) compared with patients without ATM+/-. With the exception of a poor
      performance status (P =.001), no correlation was found between ATM+/-, initial
      clinical variables, and complete remission rate; whereas a highly significant
      association was found with shorter survival (P <.0001). This cytogenetic lesion
      maintained its prognostic importance in multivariate analysis (P =.0004), along
      with performance status (P =.0006), serum lactate dehydrogenase level (P =.03),
      splenomegaly (P =.01), and histologic grade (P =.03). When analyzing indolent
      lymphomas and aggressive lymphomas separately, ATM+/- maintained its prognostic
      importance as an independent variable in both histologic groups (P =.0001 and P
      =.016, respectively). CONCLUSION: Though possibly not representing a primary
      genetic lesion in the majority of cases, the acquired ATM+/- status has
      clinicobiologic importance in NHL, possibly representing a major cytogenetic
      determinant of outcome.

PMID- 10893294
TI  - Gemcitabine in the treatment of refractory Hodgkin's disease: results of a
      multicenter phase II study.
AB  - PURPOSE: To explore the use of gemcitabine for the treatment of patients with
      relapsing or refractory Hodgkin's disease. PATIENTS AND METHODS: Eligible
      patients had measurable disease and more than one previous chemotherapy regimen.
      Patients previously treated with high-dose chemotherapy with autologous bone
      marrow or peripheral stem-cell support were not included. Gemcitabine, 1,250
      mg/m(2), was administered as a 30-minute intravenous infusion on days 1, 8, and
      15 of each 28-day cycle of therapy. The dosing schedule remained fixed, and any
      dose of gemcitabine that could not be given on time was omitted. Patients who had
      not experienced any hematologic or nonhematologic toxicity after one complete
      cycle of therapy were permitted to have subsequent doses increased by 20%: that
      is, from 1, 250 mg/m(2) to 1,500 mg/m(2). RESULTS: Of the 23 enrolled patients,
      22 were assessable for response; all 23 patients were included in the efficacy
      analysis. Disease status for two patients (9%) reached a state of complete
      remission, and seven patients (30%) achieved a partial response, for an overall
      response rate of 39% (95% confidence interval, 19.7% to 61.5%). The likelihood of
      achieving a response was not influenced by a patients' main pretreatment
      characteristics or by their response to their last prior chemotherapy. The median
      duration of response was 6.7 months (range, 2 to 33+ months), and the median
      overall survival time was 10.7 months (range, 4 to 34.7+ months). In general,
      toxicities were mild; no treatment-related deaths occurred, and only one life
      threatening adverse event was reported for this study. CONCLUSION: Gemcitabine
      was shown to be active in heavily pretreated patients with Hodgkin's disease,
      producing a response rate of 39%. Additionally, drug-related toxicities were
      mild, which thus suggests the possible inclusion of gemcitabine in an earlier
      phase of treatment.

PMID- 10893295
TI  - Leukocytosis and the retinoic acid syndrome in patients with acute promyelocytic
      leukemia treated with arsenic trioxide.
AB  - PURPOSE: Arsenic trioxide, like all-trans-retinoic acid (RA), induces
      differentiation of acute promyelocytic leukemia (APL) cells in vivo. Treatment of
      APL patients with all-trans RA is commonly associated with leukocytosis, and
      approximately 50% of patients develop the RA syndrome. We reviewed our clinical
      experience with arsenic trioxide to determine the incidence of these two
      phenomena. PATIENTS AND METHODS: Twenty-six patients with relapsed or refractory
      APL were treated with arsenic trioxide for remission induction at daily doses
      that ranged from 0.06 to 0.17 mg/kg. RESULTS: Twenty-three patients (88%)
      achieved complete remission. Leukocytosis was observed in 15 patients (58%). The
      median baseline leukocyte count for patients with leukocytosis was 3,900
      cells/microL (range, 1,200 to 72,300 cells/microL), which was higher than that
      for patients who did not develop leukocytosis (2,100 cells/microL; range, 500 to
      5,400 cells/microL; P =.01). No other cytotoxic therapy was administered, and the
      leukocytosis resolved in all cases. The RA syndrome was observed in eight
      patients (31%). Patients who developed leukocytosis were significantly more
      likely to develop the RA syndrome (P <.001), and no patient without a peak
      leukocyte count greater than 10,000 cells/microL developed the syndrome. Among
      the patients with leukocytosis, there was no observed relation between the
      leukocyte peak and the probability of developing the syndrome (P =.37).
      CONCLUSION: Induction therapy of APL with all-trans RA and arsenic trioxide is
      associated with leukocytosis and the RA syndrome. These clinical effects seem to
      be intrinsically related to the biologic responsiveness and the differentiation
      process induced by these new agents.

PMID- 10893296
TI  - Role of telomerase in normal and cancer cells.
AB  - Shortening of the telomeric DNA at chromosome ends is postulated to limit the
      lifespan of human cells. In contrast, activation of telomerase, the enzyme that
      synthesizes telomeric DNA, is proposed to be an essential step in cancer cell
      immortalization and cancer progression. This review discusses the structure and
      function of telomeres and telomerase, the role of telomerase in cell
      immortalization, and the effects of telomerase inactivation on normal and cancer
      cells. Moreover, data on the experimental use of telomerase assays for cancer
      detection and diagnosis are reviewed. Finally, the review considers the evidence
      regarding whether telomerase inhibitors could be used to treat human cancers.

PMID- 10893297
TI  - Nonmalignant diagnoses in patients. Case 1. Mediastinal lymphadenopathy
      associated with congestive heart failure.

PMID- 10893298
TI  - Nonmalignant diagnoses in patients. Case 2. Lung cancer with mediastinal
      lymphadenopathy due to amyloidosis.

PMID- 10893299
TI  - Nonmalignant diagnoses in patients. Case 3. Right atrial thrombus associated with
      a central venous catheter in a patient with metastatic adrenocortical carcinoma.

PMID- 10893300
TI  - A revisitation of "Doc, how much time do I have?".

PMID- 10893301
TI  - Ligands for glutamate receptors: design and therapeutic prospects.

PMID- 10893302
TI  - Antimalarial, antitrypanosomal, and antileishmanial activities and cytotoxicity
      of bis(9-amino-6-chloro-2-methoxyacridines): influence of the linker.
AB  - Forty bis(9-amino-6-chloro-2-methoxyacridines), in which acridine moieties are
      joined by alkanediamines, polyamines, or polyamines substituted by a side chain,
      were synthesized and tested for their in vitro activity upon the erythrocytic
      stage of Plasmodium falciparum, trypomastigote stage of Trypanosoma brucei, and
      amastigote stage of Trypanosoma cruzi and Leishmania infantum as well as for
      their cytotoxic effects upon MRC-5 cells. Results clearly showed the importance
      of the nature of the linker and of its side chain for antiparasitic activity,
      cytotoxicity, and cellular localization. Among several compounds devoid of
      cytotoxic effects at 25 microM upon MRC-5 cells, one displayed IC(50) values
      ranging from 8 to 18 nM against different P. falciparum strains while three
      others totally inhibited T. brucei at 1.56 microM.

PMID- 10893303
TI  - Identification of substituted 3-[(4,5,6, 7-tetrahydro-1H-indol-2-yl)methylene]
      1,3-dihydroindol-2-ones as growth factor receptor inhibitors for VEGF-R2 (Flk
      1/KDR), FGF-R1, and PDGF-Rbeta tyrosine kinases.
AB  - A series of new 3-substituted indolin-2-ones containing a tetrahydroindole moiety
      was developed as specific inhibitors of receptor tyrosine kinases associated with
      VEGF-R, FGF-R, and PDGF-R growth factor receptors. These compounds were evaluated
      for their inhibitory properties toward VEGF-R2 (Flk-1/KDR), FGF-R1, PDGF-Rbeta,
      p60(c)()(-)()(Src)(), and EGF-R tyrosine kinases and their ability to inhibit
      growth factor-dependent cell proliferation. Structure-activity relationships of
      this new pharmacophore have been determined at the level of kinase inhibition.
      Compounds containing a propionic acid moiety at the C-3' position of the
      tetrahydroindole ring represented the most potent indolin-2-ones to inactivate
      the VEGF, FGF, and PDGF receptor kinases. The inhibitory activities of 9d against
      VEGF-R2 (Flk-1), 9h against FGF-R1, and 9b against PDGF-Rbeta were 4, 80, and 4
      nM, respectively. However, all of these compounds were inactive when tested
      against the EGF-R tyrosine kinase. Compounds 9a and 9b represented the most
      potent inhibitors of these classes to inhibit both biochemical kinase and growth
      factor-dependent cell proliferation for these three targets. In addition,
      compound 9a was cocrystallized with the catalytic domain of FGF-R1 providing
      evidence to explain the structure-activity relationship results. This study has
      provided evidence to support the potential of these new tyrosine kinase
      inhibitors for the treatment of angiogenesis and other growth factor-related
      diseases including human cancers.

PMID- 10893304
TI  - Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit
      validation by biophysical methods, and 3D guided optimization. A promising
      alternative to random screening.
AB  - Random screening provided no suitable lead structures in a search for novel
      inhibitors of the bacterial enzyme DNA gyrase. Therefore, an alternative approach
      had to be developed. Relying on the detailed 3D structural information of the
      targeted ATP binding site, our approach combines as key techniques (1) an in
      silico screening for potential low molecular weight inhibitors, (2) a biased high
      throughput DNA gyrase screen, (3) validation of the screening hits by biophysical
      methods, and (4) a 3D guided optimization process. When the in silico screening
      was performed, the initial data set containing 350 000 compounds could be reduced
      to 3000 molecules. Testing these 3000 selected compounds in the DNA gyrase assay
      provided 150 hits clustered in 14 classes. Seven classes could be validated as
      true, novel DNA gyrase inhibitors that act by binding to the ATP binding site
      located on subunit B: phenols, 2-amino-triazines, 4-amino-pyrimidines, 2-amino
      pyrimidines, pyrrolopyrimidines, indazoles, and 2-hydroxymethyl-indoles. The 3D
      guided optimization provided highly potent DNA gyrase inhibitors, e. g., the 3,4
      disubstituted indazole 23 being a 10 times more potent DNA gyrase inhibitor than
      novobiocin (3).

PMID- 10893305
TI  - Synthesis and antitumor activity of new benzoheterocyclic derivatives of
      distamycin A.
AB  - The design, synthesis, and in vivo and in vitro antileukemic activity of a novel
      series of compounds (13-22 and 34), in which different benzoheterocyclic rings,
      bearing a nitrogen mustard or a benzoyl nitrogen mustard or an alpha
      bromoacryloyl group as alkylating moieties, are tethered to a distamycin frame,
      are reported, and structure-activity relationships are discussed. The new
      derivatives were prepared by coupling nitrogen mustard-substituted, benzoyl
      nitrogen mustard-substituted, or alpha-bromoacryloyl-substituted
      benzoheterocyclic carboxylic acids 23-32 with desformyldistamycin (33) or in one
      case with its two-pyrrole analogue 35. With very few exceptions, the activities
      of compounds bearing the same alkylating moiety are slightly affected by the kind
      of the heteroatom present on the benzoheterocyclic ring. All novel compounds,
      with one exception, showed in vitro activity against L1210 murine leukemia cell
      line comparable to or better than that of tallimustine. The compounds in which
      the nitrogen mustard and the alpha-bromoacryloyl moieties are directly linked to
      benzoheterocyclic ring showed potent cytotoxic activities (IC(50) ranging from 2
      to 14 nM), while benzoyl nitrogen mustard derivatives of benzoheterocycles showed
      reduced cytotoxic activities, and one compound (16) of this cluster was the sole
      derivative devoid of significant activity. Compound 18, a 5-nitrogen mustard N
      methylindole derivative of distamycin, showed the best antileukemic activity in
      vivo, with a very long survival time (%T/C = 457), significantly increased in
      comparison to tallimustine (%T/C = 133), and was selected for further extensive
      evaluation. Arrested polymerase chain reaction and direct DNA fragmentation
      assays were performed for compound 18 and the structurally related compounds 13
      17 and 19. The results obtained have shown that both alkylating groups and
      oligopeptide frames play a crucial role in the sequence selectivity of these
      compounds.

PMID- 10893306
TI  - Synthesis and pharmacological evaluation of new pyrazolidine-3, 5-diones as AT(1)
      angiotensin II receptor antagonists.
AB  - On the basis of the structure of the non-peptide receptor antagonist irbesartan,
      a new series of AT(1) ligands was designed. In these compounds the central
      imidazolone nucleus of irbesartan was replaced by a pyrazolidine-3,5-dione
      structure. The key intermediate N-alkylpyrazolidine-3,5-diones were synthesized
      according to a new and general method. The most active compounds possess a
      spirocyclopentane ring at position 4, a linear butyl chain at position 1, and the
      [2'-(5-tetrazolyl)biphenyl-4-yl]methyl or [2'-(benzoylaminosulfonyl)biphenyl-4
      yl]methyl group at position 2. Affinity toward the AT(1) and AT(2) receptors was
      assessed by the ability of the compounds to competitively displace [(3)H]AII from
      its specific binding sites. The most active compounds, 28 and 48, displayed high
      affinity for the AT(1) receptor, good selectivity AT(1) versus AT(2), and potent
      in vitro antagonist activity.

PMID- 10893307
TI  - [Pro(3)]Dyn A(1-11)-NH(2): a dynorphin analogue with high selectivity for the
      kappa opioid receptor.
AB  - A proline scan at positions 2 and 3 of the opioid peptide dynorphin A(1-11)-NH(2)
      led to the discovery of the analogue [Pro(3)]Dyn A(1-11)-NH(2). This analogue
      possesses high affinity and selectivity for the kappa opioid receptor
      (K(i)(kappa) = 2.7 nM, K(i) ratio kappa/micro/delta = 1/2110/3260). The gain in
      selectivity is achieved through an overall reduction of opioid receptor affinity
      which is most pronounced at micro and delta receptors. The Pro(3) analogue
      exhibits antagonist properties. Despite its high kappa affinity, [Pro(3)]Dyn A(1
      11)-NH(2) is a relatively weak antagonist in both the [(35)S]GTPgammaS assay
      (IC(50) = 380 nM) and the guinea pig ileum assay (K(e) = 244 nM). Discrepancies
      between GPI and binding assay have often been ascribed to differential kappa
      receptor subtypes prevailing in central vs peripheral neurons. Since the
      [(35)S]GTPgammaS assay uses the same membrane preparations as the binding assay,
      differential kappa subtypes can be ruled out as an explanation in this case, and
      the observed behavior rather seems to reflect an intrinsic property of the
      ligand.

PMID- 10893308
TI  - In vitro and in vivo evaluation of dihydropyrimidinone C-5 amides as potent and
      selective alpha(1A) receptor antagonists for the treatment of benign prostatic
      hyperplasia.
AB  - alpha(1) Adrenergic receptors mediate both vascular and lower urinary tract tone,
      and alpha(1) receptor antagonists such as terazosin (1b) are used to treat both
      hypertension and benign prostatic hyperplasia (BPH). Recently, three different
      subtypes of this receptor have been identified, with the alpha(1A) receptor being
      most prevalent in lower urinary tract tissue. This paper explores 4
      aryldihydropyrimidinones attached to an aminopropyl-4-arylpiperidine via a C-5
      amide as selective alpha(1A) receptor subtype antagonists. In receptor binding
      assays, these types of compounds generally display K(i) values for the alpha(1a)
      receptor subtype <1 nM while being greater than 100-fold selective versus the
      alpha(1b) and alpha(1d) receptor subtypes. Many of these compounds were also
      evaluated in vivo and found to be more potent than terazosin in both a rat model
      of prostate tone and a dog model of intra-urethral pressure without significantly
      affecting blood pressure. While many of the compounds tested displayed poor
      pharmacokinetics, compound 48 was found to have adequate bioavailability (>20%)
      and half-life (>6 h) in both rats and dogs. Due to its selectivity for the
      alpha(1a) over the alpha(1b) and alpha(1d) receptors as well as its favorable
      pharmacokinetic profile, 48 has the potential to relieve the symptoms of BPH
      without eliciting effects on the cardiovascular system.

PMID- 10893309
TI  - Characterization of a novel analogue of 1alpha,25(OH)(2)-vitamin D(3) with two
      side chains: interaction with its nuclear receptor and cellular actions.
AB  - The hormone 1alpha,25(OH)(2)-vitamin D(3) (125D) binds to its nuclear receptor
      (VDR) to stimulate gene transcription activity. Inversion of configuration at C
      20 of the side chain to generate 20-epi-1alpha,25(OH)(2)D(3) (20E-125D) increases
      transcription 200-5000-fold over 125D with its 20-normal (20N) side chain. This
      enhancement has been attributed to the VDR ligand-binding domain (LBD) having
      different contact sites for 20N and 20E side chains that generate different VDR
      conformations. We synthesized 1alpha, 25-dihydroxy-21-(3-hydroxy-3
      methylbutyl)vitamin D(3) (Gemini) with two six-carbon side chains (both 20N and
      20E orientations). Energy minimization calculations indicate the Gemini side
      chain possesses significantly more energy minima than either 125D or 20E-125D
      (2346, 207, and 127 minima, respectively). We compared activities of 125D, 20E
      125D, and Gemini, respectively, in several assays: binding to wild-type (100%,
      147%, and 38%) and C-terminal-truncated mutant VDR; transcriptional activity (of
      the transfected osteopontin promoter in ROS 17/2.8 cells: ED(50) 10, 0.005, and
      1.0 nM); mediation of conformational changes in VDR assessed by protease clipping
      (major trypsin-resistant fragment of 34, 34, and 28 kDa). For inhibition of
      cellular clonal growth of human leukemia (HL-60) and breast cancer (MCF7) cell
      lines, the ED(50)(125D)/ED(50)(Gem) was respectively 380 and 316. We conclude
      that while Gemini readily binds to the VDR and generates unique conformational
      changes, none of them is able to permit a superior gene transcription activity
      despite the presence of a 20E side chain.

PMID- 10893310
TI  - Antineoplastic agents. 443. Synthesis of the cancer cell growth inhibitor
      hydroxyphenstatin and its sodium diphosphate prodrug.
AB  - A structure-activity relationship (SAR) study of the South African willow tree
      (Combretum caffrum) antineoplastic constituent combretastatin A-4 (3b) led to the
      discovery of a potent cancer cell growth inhibitor designated phenstatin (5a).
      This benzophenone derivative of combretastatin A-4 showed remarkable
      antineoplastic activity, and the benzophenone derivative of combretastatin A-1
      was therefore synthesized. The benzophenone, designated hydroxyphenstatin (6a),
      was synthesized by coupling of a protected bromobenzene and a benzaldehyde to
      give the benzhydrol with subsequent oxidation to the ketone. Hydroxyphenstatin
      was converted to the sodium phosphate prodrug (6e) by a dibenzyl phosphite
      phosphorylation and subsequent benzyl cleavage (6a --> 6d --> 6e). While
      hydroxyphenstatin (6a) was a potent inhibitor of tubulin polymerization with
      activity comparable to that of combretastatin A-1 (3a), the phosphorylated
      derivative (6e) was inactive.

PMID- 10893311
TI  - Development of a lead inhibitor for the A16V+S108T mutant of dihydrofolate
      reductase from the cycloguanil-resistant strain (T9/94) of Plasmodium falciparum.
AB  - The Ala16Val+Ser108Thr (A16V+S108T) mutant of the Plasmodium falciparum
      dihydrofolate reductase (DHFR) is a key mutant responsible for cycloguanil
      resistant malaria due to steric interaction between Val-16 and one of the C-2
      methyl groups of cycloguanil. 4,6-Diamino-1,2-dihydrotriazines have been
      prepared, in which both methyl groups of cycloguanil are replaced by H or by H
      and an alkyl or phenyl group, and their inhibition constants against wild-type
      and mutant DHFR determined. The S108T mutation is considered to decrease
      cycloguanil binding further through the effect on the orientation of the p
      chlorophenyl group. By moving the p-chloro-substituent to the m-position in the
      chlorophenyl group, the activity against the A16V+S108T mutant enzyme is
      improved, and this effect is reinforced by the p-chloro substituent in the 3, 4
      dichlorophenyl group. A lead compound has been found with inhibitory activity
      similar to that of cycloguanil against the wild-type DHFR and about 120-fold more
      effective than cycloguanil against the A16V+S108T mutant enzyme. The activity of
      this compound against P. falciparum clone (T9/94 RC17) which harbors the
      A16V+S108T DHFR is about 85-fold greater than cycloguanil.

PMID- 10893312
TI  - '3+1' mixed-ligand oxotechnetium(V) complexes with affinity for melanoma:
      synthesis and evaluation in vitro and in vivo.
AB  - '3+1' Mixed-ligand [(99m)Tc]oxotechnetium complexes with affinity for melanoma
      were synthesized in a one-pot reaction. Complexation of technetium-99m with a
      mixture of N-R(3-azapentane-1,5-dithiol) [R = Me, Pr, Bn, Et(2)N(CH(2))(2)] and N
      (2-dialkylamino)ethanethiol [alkyl = X = Et, Bu, morpholinyl] using Sn(2+) as the
      reducing agent resulted in the formation of '3+1' mixed-ligand technetium-99m
      complexes [TcO(SN(R)S)(SNX(2))] in high radiochemical yield (60-98%). In vitro
      uptake studies in B16 murine melanoma cells indicated a moderate tumor-cell
      accumulation (40%) of compound 1 [R = Me, X = Et] and a higher accumulation (69%)
      of compound 2 [R = Me, X = Bu] after a 60-min incubation. In vivo evaluation of
      compounds 1-6 in the C57Bl6/B16 mouse melanoma model demonstrated tumor
      localization. Compound 2 displayed the highest accumulation with up to 5% ID/g at
      60 min after injection. In vivo, 2 also showed a low blood-pool activity and high
      melanoma/spleen (4.3) and melanoma/lung (1.9) ratios at 1 h. These results
      suggest that small technetium-99m complexes could be useful as potential melanoma
      imaging agents.

PMID- 10893313
TI  - Synthesis and antimalarial activity of sixteen dispiro-1,2,4, 5-tetraoxanes:
      alkyl-substituted 7,8,15,16-tetraoxadispiro[5.2.5. 2]hexadecanes.
AB  - Sixteen alkyl-substituted dispiro-1,2,4,5-tetraoxanes (7,8,15, 16
      tetraoxadispiro[5.2.5.2]hexadecanes) were synthesized to explore dispiro-1,2,4,5
      tetraoxane SAR and to identify tetraoxanes with better oral antimalarial activity
      than prototype tetraoxane 1 (WR 148999). The tetraoxanes were prepared either by
      peroxidation of the corresponding cyclohexanone derivatives in H(2)SO(4)/CH(3)CN
      or by ozonolysis of the corresponding cyclohexanone methyl oximes. Those
      tetraoxanes with alkyl substituents at the 1 and 10 positions were formed as
      single stereoisomers, whereas the five tetraoxanes formed without the
      stereochemical control provided by alkyl groups at the 1 and 10 positions were
      isolated as mixtures of diastereomers. Three of the sixteen tetraoxanes were
      inactive (IC(50)'s > 1000 nM), but five (2, 6, 10, 11, 12) had IC(50)'s between
      10 and 30 nM against the chloroquine-sensitive D6 and chloroquine-resistant W2
      clones of Plasmodium falciparum compared to corresponding IC(50)'s of 55 and 32
      nM for 1 and 8.4 and 7.3 nM for artemisinin. We suggest that tetraoxanes 13, 16,
      and 17 were inactive and tetraoxanes 4 and 7 were weakly active due to steric
      effects preventing or hindering peroxide bond access to parasite heme.
      Tetraoxanes 1, 10, 11, and 14, along with artemisinin and arteether as controls,
      were administered po b.i.d. (128 mg/kg/day) to P. berghei-infected mice on days
      3, 4, and 5 post-infection. At this dose, tetraoxanes 10, 11, and 14 cured
      between 40% and 60% of the infected animals. In comparison, artemisinin and
      tetraoxane 1 produced no cures, whereas arteether cured 100% of the infected
      animals. There was no apparent relationship between tetraoxane structure and in
      vitro neurotoxicity, nor was there any correlation between antimalarial activity
      and neurotoxicity for these seventeen tetraoxanes.

PMID- 10893314
TI  - Potent and selective indolomorphinan antagonists of the kappa-opioid receptor.
AB  - The indole moiety in the delta-opioid antagonist, naltrindole (2, NTI), was
      employed as a scaffold to hold an "address" for interaction with the kappa-opioid
      receptor. The attachment of the address to the 5'-position of the indole moiety
      was based on superposition of NTI upon the kappa antagonist, norbinaltorphimine
      (1, norBNI). A variety of cationic groups were employed as a kappa address in an
      effort to investigate its interaction with the anionic address subsite, Glu297,
      on the kappa receptor. Some of the groups that were employed for this purpose
      were amines, amidines, guanidines, and quaternary ammonium. Members of the series
      were found to have a varying degree of kappa antagonist potency and kappa
      selectivity when tested in smooth muscle preparations. The 5'-guanidine
      derivative 12a (GNTI) was the most potent member of the series and had the
      highest kappa selectivity ratio. GNTI was 2 times more potent and 6-10-fold more
      selective than norBNI (1). In general, the order of potency in the series was:
      guanidines > amidines approximately quaternary ammonium > amines. The kappa
      antagonist potency appeared to be a function of a combination of the pK(a) and
      distance constraint of the cationic substituent of the ligand. Receptor binding
      studies were qualitatively in agreement with the pharmacological data. Molecular
      modeling studies on 12a suggested that the protonated N-17 and guanidinium groups
      of GNTI are associated with Asp138 (TM3) and Glu297 (TM6), respectively, while
      the phenolic hydroxyl may be involved in donor-acceptor interactions with the
      imidazole ring of His291. It was concluded that the basis for the high kappa
      selectivity of GNTI is related both to association with the nonconserved Glu297
      residue and to unfavorable interactions with an equivalent position in mu- and
      delta-opioid receptors.

PMID- 10893315
TI  - A rapid computational method for lead evolution: description and application to
      alpha(1)-adrenergic antagonists.
AB  - The high failure rate of drugs in the development phase requires a strategy to
      reduce risks by generating lead candidates from different chemical classes. We
      describe a new three-dimensional computational approach for lead evolution, based
      on multiple pharmacophore hypotheses. Using full conformational models for both
      active and inactive compounds, a large number of pharmacophore hypotheses are
      analyzed to select the set or "ensemble" of hypotheses that, when combined, is
      most able to discriminate between active and inactive molecules. The ensemble
      hypothesis is then used to search virtual chemical libraries to identify
      compounds for synthesis. This method is very rapid, allowing very large virtual
      libraries on the order of a million compounds to be filtered efficiently. In
      applying this method to alpha(1)-adrenergic receptor ligands, we have
      demonstrated lead evolution from heterocyclic alpha(1)-adrenergic receptor
      ligands to highly dissimilar active N-substituted glycine compounds. Our results
      also show that the active N-substituted glycines are part of our smaller filtered
      library and thus could have been identified by synthesizing only a portion of the
      N-substituted glycine library.

PMID- 10893316
TI  - Somatotropin increases protein balance independent of insulin's effects on
      protein metabolism in growing pigs.
AB  - Somatotropin (ST) administration enhances protein deposition and elicits profound
      metabolic responses, including hyperinsulinemia. To determine whether the
      anabolic effect of ST is due to hyperinsulinemia, pair-fed weight-matched growing
      swine were treated with porcine ST (150 microg x kg body wt(-1) x day(-1)) or
      diluent for 7 days (n = 6/group, approximately 20 kg). Then pancreatic glucose
      amino acid clamps were performed after an overnight fast. The objective was to
      reproduce the insulin levels of 1) fasted control and ST pigs (basal insulin, 5
      microU/ml), 2) fed control pigs (low insulin, 20 microU/ml), and 3) fed ST pigs
      (high insulin, 50 microU/ml). Amino acid and glucose disposal rates were
      determined from the infusion rates necessary to maintain preclamp blood levels of
      these substrates. Whole body nonoxidative leucine disposal (NOLD), leucine
      appearance (R(a)), and leucine oxidation were determined with primed, continuous
      infusions of [(13)C]leucine and [(14)C]bicarbonate. ST treatment was associated
      with higher NOLD and protein balance and lower leucine oxidation and amino acid
      and glucose disposals. Insulin lowered R(a) and increased leucine oxidation,
      protein balance, and amino acid and glucose disposals. These effects of insulin
      were suppressed by ST treatment; however, the protein balance remained higher in
      ST pigs. The results show that ST treatment inhibits insulin's effects on protein
      metabolism and indicate that the stimulation of protein deposition by ST
      treatment is not mediated by insulin. Comparison of the protein metabolic
      responses to ST treatment during the basal fasting period with those in the fully
      fed state from a previous study suggests that the mechanism by which ST treatment
      enhances protein deposition is influenced by feeding status.

PMID- 10893317
TI  - Effects of simulated hyperglycemia, insulin, and glucagon on endothelial nitric
      oxide synthase expression.
AB  - Diabetes is associated with endothelial dysfunction and increased risk of
      hypertension, cardiovascular disease, and renal complications. Earlier studies
      have revealed that hyperglycemia impairs nitric oxide (NO) production and
      diabetes causes endothelial dysfunction in humans and experimental animals. This
      study was designed to test the effects of altered concentrations of glucose,
      insulin, and glucagon, the principal variables in types I and II diabetes, on NO
      production and endothelial NO synthase (eNOS) expression in cultured human
      coronary endothelial cells. Cultured endothelial cells were incubated in the
      presence of glucose at either normal (5.6 mM) or high (25 mM) concentrations for
      7 days. The rates of basal and bradykinin-stimulated NO production (nitrate +
      nitrite) and eNOS protein expression (Western blot) were then determined at the
      basal condition and in the presence of insulin (10(-8) and 10(-7) M), glucagon
      (10(-8) and 10(-7) M), or both. Incubation with a high-glucose concentration for
      7 days significantly downregulated, whereas insulin significantly upregulated,
      basal and bradykinin-stimulated NO production and eNOS expression in cultured
      endothelial cells. The stimulatory action of insulin was mitigated by high
      glucose concentration and abolished by cotreatment of cells with glucagon. Thus
      hyperglycemia, insulinopenia, and hyperglucagonemia, which frequently coexist in
      diabetes, can work in concert to suppress NO production by human coronary artery
      endothelial cells.

PMID- 10893318
TI  - Endothelin-1 in hypertension in the baroreflex-intact SHR: a role independent
      from vasopressin release.
AB  - This study sought to identify whether central endothelin (ET) receptor activation
      contributes to the elevated pressure in spontaneously hypertensive rats (SHR) and
      whether an ET-stimulated vasopressin (AVP) release mediates the increased
      pressure. In Wistar Kyoto (WKY) rats, intracerebroventricular ET-1 induced a dose
      dependent pressor response that was shifted rightward in SHR. ET(A) antagonism
      decreased mean arterial pressure in baroreflex-intact SHR (P<0.01), consistent
      with inhibition of endogenous ET-1, and blocked the pressor response to exogenous
      ET-1 in both strains. ET-1 increased AVP only after sinoaortic denervation
      (P<0.05). Contrary to WKY, sinoaortic denervation was required to elicit a
      significant pressor response with 5 pmol ET-1 in SHR. Sinoaortic denervation
      permitted ET-1 to increase AVP in both strains, and peripheral V(1) blockade
      decreased pressure in denervated but not intact rats. After nitroprusside
      normalized pressure in SHR, the pressor and AVP secretory responses paralleled
      those in WKY. Thus endogenous ET(A) receptor mechanisms contribute to
      hypertension, independent of AVP, in baroreflex-intact SHR. Although blunted in
      the hypertensive state, the arterial baroreflex buffers the ET-1-induced pressor
      and AVP secretory responses in both strains.

PMID- 10893319
TI  - Induction of Ca-independent PLA(2) and conservation of plasmalogen
      polyunsaturated fatty acids in diabetic heart.
AB  - Diabetes-induced changes in phospholipase A(2) (PLA(2)) activity have been
      measured in several tissues but are undefined in diabetic myocardium. We measured
      ventricular PLA(2) activity in control, streptozotocin-induced diabetic, and
      insulin-treated diabetic rats and characterized myocardial phospholipids to
      determine whether diabetes altered myocardial phospholipid metabolism. Increased
      membrane-associated Ca(2+)-independent PLA(2) (iPLA(2)) activity was observed in
      diabetes that was selective for arachidonylated phospholipids. Increased iPLA(2)
      activity was accompanied by an increase in choline lysophospholipids. Diabetes
      was associated with marked alterations in the phospholipid composition of the
      myocardium, characterized by decreases in esterified arachidonic and
      docosahexaenoic acids and increases in linoleic acid. The decrease in
      polyunsaturated fatty acids was confined to diacylphospholipids, whereas the
      relative amount of these fatty acids in plasmalogens was increased. Diabetes
      induced changes in PLA(2) activity, lysophospholipid production, and alterations
      in phospholipid composition were all reversed by insulin treatment of diabetic
      animals. Diabetes-induced changes in membrane phospholipid content and
      phospholipid hydrolysis may contribute to some of the alterations in myocardial
      function that are observed in diabetic patients.

PMID- 10893320
TI  - Energetic response to repeated restraint stress in rapidly growing mice.
AB  - There is a cost of stress that may result in the loss of normal biological
      function (e.g., growth). Repeated, and even single, applications of stressors
      have been shown to induce negative energy balance in rodents. However, here we
      addressed whether this energetic response changes during multiple stress exposure
      and whether there is complete recovery subsequent to the cessation of stress
      exposure. These questions were addressed in growing C57Bl/6 mice (31 day) by
      determining at different times the energetic and endocrine responses after the
      exposure to restraint (R) stress for 4 h applied once (R1), repeatedly over 3
      days (R3), or repeatedly over 7 days (R7). Compared with control values, R
      elevated (P<0.05) plasma corticosterone and reduced plasma insulin-like growth
      factor I on all days of exposure to the stressor. Seven days, but not 1 or 3 days
      of R, decreased the net growth (126%, P<0.05) and deposition of fat (71%, P<0.05)
      and lean (60%, P<0.05) energy over the 7 days. Only R7 depressed the 7-day
      metabolizable energy intake (P<0.05), and R7, but not R1 or R3, increased the
      overall energy expenditure (10%, P<0.05). Our results demonstrate that repeated
      episodes of stress are energetically costly to the rapidly growing animal, but
      compensatory mechanisms mitigate this cost of repeated stress exposure and permit
      complete recovery of energy balance after the cessation of stress application.

PMID- 10893321
TI  - Summation of behavioral and immunological stress: metabolic consequences to the
      growing mouse.
AB  - To address the hypothesis that multiple stressors can have cumulative effects on
      the individual, we determined the effects of restraint (R) stress (4 h/day for 7
      days), immunological (L) stress [lipopolysaccharide (LPS) injection, 0.45
      microg/g body wt on days 6 and 7], and R + L (RL) on the growth and energetics of
      C57Bl/6 male mice. R and L each repeatedly increased (P<0.05) circulating
      corticosterone (>8 times), but RL caused even greater (>250%, P<0. 05)
      concentrations of circulating corticosterone than did either stressor alone. Only
      L and RL increased (P<0.05) circulating interleukin-1beta. Although R, L, and RL
      impaired growth (>75% below controls, P<0.05), RL reduced growth to a greater
      extent. All stressors inhibited (P<0.05) lean (>33% below controls) and fat
      (>120% below controls) energy deposition, and like the effects on growth,
      combined RL stress inhibited lean and fat energy deposition to a greater extent
      than did either stressor acting alone. These results demonstrated that the
      summation of multiple stress results in a cumulative cost to the growing animal.

PMID- 10893322
TI  - Effects of nicotinic acid on fatty acid kinetics, fuel selection, and pathways of
      glucose production in women.
AB  - Chronic nicotinic acid (NA) ingestion effectively lowers lipid levels, but
      adverse effects on glucose metabolism have been reported. Our goal was to
      investigate acute and chronic effects of NA on lipolysis and glucose metabolism
      in women. Healthy normolipidemic volunteers (n = 5) were studied twice; four-day
      hospital stays were separated by 1 mo, during which time subjects took increasing
      doses of NA to 2 g/day (500 mg, 4 times). In the second study, 500 mg of NA was
      given at 0800. Rates of appearance (R(a)) of free fatty acid (FFA), glycerol, and
      glucose were determined by isotope dilution (of [1,2,3,4-(13)C(4)]palmitate, [2
      (13)C(1)]glycerol, and [U-(13)C(6)]glucose). Mass isotopomer distribution
      analysis was used to measure gluconeogenesis and glycogenolysis. Fasting FFA
      concentrations ([FFA]), R(a) FFA, and R(a) glycerol were nonsignificantly
      elevated after 1 mo. Acute NA induced a significant reduction followed by a
      rebound overshoot of [FFA], R(a) FFA, and R(a) glycerol. Whole body fat oxidation
      fell initially and then increased back to basal levels; endogenous glucose
      production (EGP) increased in parallel with carbohydrate oxidation and then
      returned to basal values. The increased EGP was due entirely to increased
      glycogenolysis, not gluconeogenesis. We conclude that chronic effects of NA on
      FFA metabolism are complex (acute suppression followed by overshoot of R(a) FFA
      and [FFA] on top of a trend toward basal elevations), that responses after NA are
      consistent with operation of a glucose-fatty acid cycle in peripheral tissues,
      and that secondary effects on EGP were through changes in glycogenolysis, not
      gluconeogenesis.

PMID- 10893323
TI  - Parathyroid hormone-related protein induces G1 phase growth arrest of vascular
      smooth muscle cells.
AB  - In this study, we investigated the mechanisms responsible for the growth
      inhibitory action of parathyroid hormone-related protein (PTHRP) in A10 vascular
      smooth muscle cells (VSMC). Fluorescence-activated cell sorting analysis of serum
      stimulated VSMC treated with PTHRP or dibutyryl-cAMP (DBcAMP) demonstrated an
      enrichment of cells in G1 and a reduction in the S phase. Measurement of DNA
      synthesis in platelet-derived growth factor-stimulated VSMC treated with DBcAMP
      revealed that cells became refractory to growth inhibition by 12-16 h, consistent
      with blockade in mid-G1. cAMP treatment blunted the serum-induced rise in cyclin
      D1 during cell cycle progression without altering levels of the cyclin-dependent
      kinase cdk4 or cyclin E and its associated kinase, cdk2. Exposure of cells to
      PTHRP or cAMP resulted in a reduction in retinoblastoma gene product (Rb)
      phosphorylation. Immunoblotting of extracts from cAMP-treated cells with
      antibodies to cdk inhibitors revealed a striking increase in p27(kip1) abundance
      coincident with the G1 block. Immunoprecipitation with an anti-cyclin D1 antibody
      of cell lysates prepared from cAMP-treated cells followed by immunoblotting with
      antisera to p27(kip1) disclosed a threefold increase in p27(kip1) associated with
      cyclin D1 compared with lysates treated with serum alone. We conclude that PTHRP,
      by increasing intracellular cAMP, induces VSMC cycle arrest in mid-G1. This
      occurs secondary to a suppression in cyclin D1 and induction of p27(kip1)
      expression, which in turn inhibits Rb phosphorylation.

PMID- 10893324
TI  - beta-cell adaptation in 60% pancreatectomy rats that preserves normoinsulinemia
      and normoglycemia.
AB  - Islet beta-cells are the regulatory element of the glucose homeostasis system.
      When functioning normally, they precisely counterbalance changes in insulin
      sensitivity or beta-cell mass to preserve normoglycemia. This understanding seems
      counter to the dogma that beta-cells are regulated by glycemia. We studied 60%
      pancreatectomy rats (Px) 4 wk postsurgery to elucidate the beta-cell adaptive
      mechanisms. Nonfasting glycemia and insulinemia were identical in Px and sham
      operated controls. There was partial regeneration of the excised beta-cells in
      the Px rats, but it was limited in scope, with the pancreas beta-cell mass
      reaching 55% of the shams (40% increase from the time of surgery). More
      consequential was a heightened glucose responsiveness of Px islets so that
      glucose utilization and insulin secretion per milligram of islet protein were
      both 80% augmented at normal levels of glycemia. Investigation of the biochemical
      basis showed a doubled glucokinase maximal velocity in Px islets, with no change
      in the glucokinase protein concentration after adjustment for the different beta
      cell mass in Px and sham islets. Hexokinase activity measured in islet extracts
      was also minimally increased, but the glucose 6-phosphate concentration and basal
      glucose usage of Px islets were not different from those in islets from sham
      operated rats. The dominant beta-cell adaptive response in the 60% Px rats was an
      increased catalytic activity of glucokinase. The remaining beta-cells thus sense,
      and respond to, perceived hyperglycemia despite glycemia actually being normal.
      beta-Cell mass and insulin secretion are both augmented so that whole pancreas
      insulin output, and consequently glycemia, are maintained at normal levels.

PMID- 10893325
TI  - Glucocorticoids abate p70(S6k) and eIF4E function in L6 skeletal myoblasts.
AB  - The catabolic properties of glucocorticoid hormones are largely attributable to
      dual regulation of protein degradation and synthesis. With regard to the latter,
      glucocorticoids modulate the translational machinery, namely that component
      functional in translation initiation. This investigation revealed that in L6
      myoblasts, dexamethasone, a synthetic glucocorticoid, deactivated the ribosomal
      protein S6 kinase (p70(S6k)) within 4 h, as evidenced by diminished
      phosphorylation of its physiological substrate, the 40S ribosomal protein S6.
      This deactivation correlated with dephosphorylation of p70(S6k) at Thr(389),
      whereas phosphorylation of Ser(411) was unaffected. Furthermore, glucocorticoid
      administration induced dephosphorylation of the cap-dependent translational
      repressor, eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1),
      thereby facilitating conjunction of the inhibitor and eIF4E. The mechanism of
      action is reminiscent of classical transcriptional regulation by steroid hormone
      receptors in that these effects were preceded by a temporal lag and were
      sensitive to inhibitors of glucocorticoid receptor function as well as
      transcriptional and translational inhibition. Okadaic acid and calyculin A
      corrected the dexamethasone-induced dephosphorylation of p70(S6k) and 4E-BP1,
      implicating a PP1- and/or PP2A-like protein phosphatase(s) in the observed
      phenomena. Hence, glucocorticoids attenuate distal constituents of the
      phosphatidylinositol-3 kinase signaling pathway and thereby encumber the protein
      synthetic apparatus.

PMID- 10893326
TI  - Fetal origins of hyperphagia, obesity, and hypertension and postnatal
      amplification by hypercaloric nutrition.
AB  - Environmental factors and diet are generally believed to be accelerators of
      obesity and hypertension, but they are not the underlying cause. Our animal model
      of obesity and hypertension is based on the observation that impaired fetal
      growth has long-term clinical consequences that are induced by fetal programming.
      Using fetal undernutrition throughout pregnancy, we investigated whether the
      effects of fetal programming on adult obesity and hypertension are mediated by
      changes in insulin and leptin action and whether increased appetite may be a
      behavioral trigger of adult disease. Virgin Wistar rats were time mated and
      randomly assigned to receive food either ad libitum (AD group) or at 30% of ad
      libitum intake, or undernutrition (UN group). Offspring from UN mothers were
      significantly smaller at birth than AD offspring. At weaning, offspring were
      assigned to one of two diets [a control diet or a hypercaloric (30% fat) diet].
      Food intake in offspring from UN mothers was significantly elevated at an early
      postnatal age. It increased further with advancing age and was amplified by
      hypercaloric nutrition. UN offspring also showed elevated systolic blood pressure
      and markedly increased fasting plasma insulin and leptin concentrations. This
      study is the first to demonstrate that profound adult hyperphagia is a
      consequence of fetal programming and a key contributing factor in adult
      pathophysiology. We hypothesize that hyperinsulinism and hyperleptinemia play a
      key role in the etiology of hyperphagia, obesity, and hypertension as a
      consequence of altered fetal development.

PMID- 10893327
TI  - Glucagon-like peptide-1 improves insulin and proinsulin binding on RINm5F cells
      and human monocytes.
AB  - Glucagon-like peptide-1-(7---36) amide (GLP-1) is a potent incretin hormone
      secreted from distal gut. It stimulates basal and glucose-induced insulin
      secretion and proinsulin gene expression. The present study tested the hypothesis
      that GLP-1 may modulate insulin receptor binding. RINm5F rat insulinoma cells
      were incubated with GLP-1 (0.01-100 nM) for different periods (1 min-24 h).
      Insulin receptor binding was assessed by competitive ligand binding studies. In
      addition, we investigated the effect of GLP-1 on insulin receptor binding on
      monocytes isolated from type 1 and type 2 diabetes patients and healthy
      volunteers. In RINm5F cells, GLP-1 increased the capacity and affinity of insulin
      binding in a time- and concentration-dependent manner. The GLP-1 receptor agonist
      exendin-4 showed similar effects, whereas the receptor antagonist exendin-(9--
      39) amide inhibited the GLP-1-induced increase in insulin receptor binding. The
      GLP-1 effect was potentiated by the adenylyl cyclase activator forskolin and the
      stable cAMP analog Sp-5, 6-dichloro-1-beta-D-ribofuranosyl-benzimidazole-3', 5'
      monophosphorothioate but was antagonized by the intracellular Ca(2+) chelator 1,2
      bis(0-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM. Glucagon, gastric
      inhibitory peptide (GIP), and GIP-(1---30) did not affect insulin binding. In
      isolated monocytes, 24 h incubation with 100 nM GLP-1 significantly (P<0.05)
      increased the diminished number of high-capacity/low-affinity insulin binding
      sites per cell in type 1 diabetics (9,000+/-3,200 vs. 18,500+/-3,600) and in type
      2 diabetics (15,700+/-2,100 vs. 28,900+/-1,800) compared with nondiabetic control
      subjects (25,100+/-2,700 vs. 26,200+/-4,200). Based on our previous experiments
      in IEC-6 cells and IM-9 lymphoblasts indicating that the low-affinity/high
      capacity insulin binding sites may be more specific for proinsulin (Jehle, PM,
      Fussgaenger RD, Angelus NK, Jungwirth RJ, Saile B, and Lutz MP. Am J Physiol
      Endocrinol Metab 276: E262-E268, 1999 and Jehle, PM, Lutz MP, and Fussgaenger RD.
      Diabetologia 39: 421-432, 1996), we further investigated the effect of GLP-1 on
      proinsulin binding in RINm5F cells and monocytes. In both cell types, GLP-1
      induced a significant increase in proinsulin binding. We conclude that, in RINm5F
      cells and in isolated human monocytes, GLP-1 specifically increases the number of
      high-capacity insulin binding sites that may be functional proinsulin receptors.

PMID- 10893328
TI  - Chronic blockade of NO synthase paradoxically increases islet NO production and
      modulates islet hormone release.
AB  - Islet production of nitric oxide (NO) and CO in relation to islet hormone
      secretion was investigated in mice given the NO synthase (NOS) inhibitor N(G)
      nitro-L-arginine methyl ester (L-NAME) in their drinking water. In these mice,
      the total islet NO production was paradoxically increased, reflecting induction
      of inducible NOS (iNOS) in background of reduced activity and immunoreactivity of
      constitutive NOS (cNOS). Unexpectedly, normal mice fasted for 24 h also displayed
      iNOS activity, which was further increased in L-NAME-drinking mice. Glucose
      stimulated insulin secretion in vitro and in vivo was increased in fasted but
      unaffected in fed mice after L-NAME drinking. Glucagon secretion was increased in
      vitro. Control islets incubated with different NOS inhibitors at 20 mM glucose
      displayed increased insulin release and decreased cNOS activity. These NOS
      inhibitors potentiated glucose-stimulated insulin release also from islets of L
      NAME-drinking mice. In contrast, glucagon release was suppressed. In islets from
      L-NAME-drinking mice, cyclic nucleotides were upregulated, and forskolin
      stimulated hormone release, CO production, and heme oxygenase (HO)-2 expression
      increased. In conclusion, chronic NOS blockade evoked iNOS-derived NO production
      in pancreatic islets and elicited compensatory mechanisms against the inhibitory
      action of NO on glucose-stimulated insulin release by inducing upregulation of
      the islet cAMP and HO-CO systems.

PMID- 10893329
TI  - Hepatic glucose metabolism during intraduodenal glucose infusion: impact of
      infection.
AB  - We previously reported that infection decreases hepatic glucose uptake when
      glucose is given as a constant peripheral glucose infusion (8 mg. kg(-1) x min(
      1)). This impairment persisted despite greater hyperinsulinemia in the infected
      group. In a normal setting, hepatic glucose uptake can be further enhanced if
      glucose is given gastrointestinally. Thus the aim of this study was to determine
      whether hepatic glucose uptake is impaired during an infection when glucose is
      given gastrointestinally. Thirty-six hours before study, a sham (SH, n = 7) or
      Escherichia coli-containing (2 x 10(9) organisms/kg; INF; n = 7) fibrin clot was
      placed in the peritoneal cavity of chronically catheterized dogs. After the 36 h,
      a glucose bolus (150 mg/kg) followed by a continuous infusion (8 mg. kg(-1). min(
      1)) of glucose was given intraduodenally to conscious dogs for 240 min. Tracer
      ([3-(3)H]glucose and [U-(14)C]glucose) and arterial-venous difference techniques
      were used to assess hepatic and intestinal glucose metabolism. Infection
      increased hepatic blood flow (35 +/- 5 vs. 47+/-3 ml x g(-1) x min(-1); SH vs.
      INF) and basal glucose rate of appearance (2.1+/-0.2 vs. 3.3+/-0.1 mg x kg(-1) x
      min(-1)). Arterial insulin concentrations increased similarly in SH and INF
      during the last hour of glucose infusion (38+/-8 vs. 46+/-20 microU/ml), and
      arterial glucagon concentrations fell (62+/-14 to 30+/-3 vs. 624+/-191 to 208+/
      97 pg/ml). Net intestinal glucose absorption was decreased in INF, attenuating
      the increase in blood glucose caused by the glucose load. Despite this, net
      hepatic glucose uptake (1.6+/-0.8 vs. 2.4+/- 0.9 mg x kg(-1) x min(-1); SH vs.
      INF) and consequently tracer-determined glycogen synthesis (1.3+/-0.3 vs. 1.0+/
      0.3 mg. kg(-1) x min(-1)) were similar between groups. In summary, infection
      impairs net glucose absorption, but not net hepatic glucose uptake or glycogen
      deposition, when glucose is given intraduodenally.

PMID- 10893330
TI  - Biological activities of recombinant chicken leptin C4S analog compared with
      unmodified leptins.
AB  - The chicken leptin sequence, in contrast to mammalian leptins, contains an
      unpaired Cys at position 3 of the original cDNA (AF012727). The presence of an
      extra Cys may confer a different structure and affect the leptin's biological
      activity. To address this, we studied the effects of wild-type and mutated (C4S)
      chicken leptins in vitro and in vivo and compared them with mammalian leptin
      prepared from ovine leptin cDNA. The prokaryotic expression vector pMON, encoding
      full-size A(-1) chicken leptin (AF012727), was mutated using a mutagenesis kit,
      yielding the C4S analog. Escherichia coli cells transformed with this vector
      overexpressed large amounts of chicken leptin C4S upon induction with nalidixic
      acid. The expressed protein, found in the inclusion bodies, was refolded and
      purified to homogeneity on a Q-Sepharose column, yielding three
      electrophoretically pure fractions, eluted from the column by 100, 125, and 150
      mM NaCl, respectively. All three fractions showed a single band of the expected
      molecular mass (16 kDa) and were composed of >95% monomeric protein. Proper
      refolding was evidenced by comparing the circular dichroism spectrum of the
      analog with spectra of nonmutated chicken and ovine leptins. The biological
      activity of the C4S analog was evidenced by its ability to stimulate
      proliferation of leptin-sensitive BAF/3 cells transfected with a long form of
      human leptin receptor construct similar to its nonmutated counterpart, indicating
      that Cys4 plays no role in leptin activity. The in vitro activity of both wild
      type and mutated chicken leptins was approximately 10-fold lower than that of
      ovine leptin. After intravenous or intraperitoneal injections, C4S analog and the
      nonmutated chicken and ovine leptins all lowered the food intake of starved 9-day
      old broiler or 5-wk-old layer male chickens by 11-34%. Monitoring food behavior
      revealed that the attenuated food intake resulted not from a decreased number of
      approaches to the feeders but from a decrease in the average time spent eating
      during each approach.

PMID- 10893331
TI  - Weight loss in postmenopausal obesity: no adverse alterations in body composition
      and protein metabolism.
AB  - We sought to determine if decrements in the mass of fat-free body mass (FFM) and
      other lean tissue compartments, and related changes in protein metabolism, are
      appropriate for weight loss in obese older women. Subjects were 14 healthy weight
      stable obese (BMI > or =30 kg/m(2)) postmenopausal women >55 yr who participated
      in a 16-wk, 1, 200 kcal/day nutritionally complete diet. Measures at baseline and
      16 wk included FFM and appendicular lean soft tissue (LST) by dual-energy X-ray
      absorptiometry; body cell mass (BCM) by (40)K whole body counting; total body
      water (TBW) by tritium dilution; skeletal muscle (SM) by whole body MRI; and
      fasting whole body protein metabolism through L-[1-(13)C]leucine kinetics. Mean
      weight loss (+/-SD) was 9.6+/-3.0 kg (P<0.0001) or 10.7% of initial body weight.
      FFM decreased by 2.1+/-2.6 kg (P = 0.006), or 19.5% of weight loss, and did not
      differ from that reported (2.3+/-0.7 kg). Relative losses of SM, LST, TBW, and
      BCM were consistent with reductions in body weight and FFM. Changes in
      [(13)C]leucine flux, oxidation, and synthesis rates were not significant. Follow
      up of 11 subjects at 23.7 +/-5.7 mo showed body weight and fat mass to be below
      baseline values; FFM was nonsignificantly reduced. Weight loss was accompanied by
      body composition and protein kinetic changes that appear appropriate for the
      magnitude of body mass change, thus failing to support the concern that diet
      induced weight loss in obese postmenopausal women produces disproportionate LST
      losses.

PMID- 10893332
TI  - Aldosterone- and testosterone-mediated intracellular calcium response in skeletal
      muscle cell cultures.
AB  - Fast nongenomic steroid actions in several cell types seem to be mediated by
      second messengers such as intracellular calcium ([Ca(2+)](i)) and inositol 1,4,5
      trisphosphate (IP(3)). We have shown the presence of both slow calcium transients
      and IP(3) receptors associated with cell nuclei in cultured skeletal muscle
      cells. The effect of steroids on [Ca(2+)](i) was monitored in Fluo 3
      acetoxymethyl ester-loaded myotubes by either confocal microscopy or fluorescence
      microscopy, with the use of out-of-focus fluorescence elimination. The mass of
      IP(3) was determined by radioreceptor displacement assay. [Ca(2+)](i) changes
      after either aldosterone (10-100 nM) or testosterone (50-100 nM) were observed; a
      relatively fast (<2 min) calcium transient, frequently accompanied by
      oscillations, was evident with both hormones. A slow rise in [Ca(2+)](i) that
      reached its maximum after a 30-min exposure to aldosterone was also observed.
      Calcium responses seem to be fairly specific for aldosterone and testosterone,
      because several other steroid hormones do not induce detectable changes in
      fluorescence, even at 100-fold higher concentrations. The mass of IP(3) increased
      transiently to reach two- to threefold the basal level 45 s after addition of
      either aldosterone or testosterone, and the IP(3) transient was more rapid than
      the fast calcium signal. Spironolactone, an inhibitor of the intracellular
      aldosterone receptor, or cyproterone acetate, an inhibitor of the testosterone
      receptor, had no effect on the fast [Ca(2+)](i) signal or in the increase in
      IP(3) mass. These signals could mean that there are distinct nongenomic pathways
      for the action of these two steroids in skeletal muscle cells.

PMID- 10893333
TI  - Involvement of tyrosine kinase in citrate-stimulated aldosterone production in
      bovine glomerulosa cells.
AB  - The present study was designed to assess whether citrate stimulates aldosterone
      production by isolated bovine adrenal glomerulosa cells in vitro. When the cells
      were incubated with graded concentrations of citrate up to 4.0 mM, basal
      aldosterone production was significantly elevated, with a gradual reduction of
      extracellular ionized calcium concentration. Without citrate, however, adding
      increasing amounts of calcium chloride to a calcium-free medium did not reproduce
      the citrate's effect on basal aldosterone production. Genistein, an inhibitor of
      tyrosine kinases, inhibited the citrate (4 mM)-induced aldosterone production in
      a dose-dependent manner, with 89.8% of inhibition at a concentration of 10
      microM. When the cells were exposed to citrate (4 mM) for 5, 10, and 30 min,
      tyrosine in Mr 105,000 endogenous protein was dominantly phosphorylated. This
      study demonstrates for the first time that citrate stimulates aldosterone
      production in bovine adrenal glomerulosa cells in vitro and also suggests a
      crucial involvement of protein tyrosine kinase in the steroidogenic action of
      citrate in the cells.

PMID- 10893334
TI  - Plasma FFA utilization and fatty acid-binding protein content are diminished in
      type 2 diabetic muscle.
AB  - In this study, we investigated the hypothesis that impairments in forearm
      skeletal muscle free fatty acid (FFA) metabolism are present in patients with
      type 2 diabetes both in the overnight fasted state and during beta-adrenergic
      stimulation. Eight obese subjects with type 2 diabetes and eight nonobese
      controls (Con) were studied using the forearm balance technique and indirect
      calorimetry during infusion of the stable isotope tracer [U-(13)C]palmitate after
      an overnight fast and during infusion of the nonselective beta-agonist
      isoprenaline (Iso, 20 ng. kg lean body mass(-1) x min(-1)). Additionally,
      activities of mitochondrial enzymes and of cytoplasmatic fatty acid-binding
      protein (FABP) were determined in biopsies from the vastus lateralis muscle. Both
      during fasting and Iso infusion, the tracer balance data showed that forearm
      muscle FFA uptake (Con vs. type 2: fast 449+/-69 vs. 258 +/-42 and Iso 715+/-129
      vs. 398+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05) and FFA release were
      lower in type 2 diabetes compared with Con. Also, the oxidation of plasma FFA by
      skeletal muscle was blunted during Iso infusion in type 2 diabetes (Con vs. type
      2: Iso 446 +/- 274 vs. 16+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05). The
      net forearm glycerol release was increased in type 2 diabetic subjects (P< 0.05),
      which points to an increased forearm lipolysis. Additionally, skeletal muscle
      cytoplasmatic FABP content and the activity of muscle oxidative enzymes were
      lowered in type 2 diabetes. We conclude that the uptake and oxidation of plasma
      FFA are impaired in the forearm muscles of type 2 diabetic subjects in the
      overnight fasted state with and without Iso stimulation.

PMID- 10893335
TI  - Renal resistance to vasopressin in poorly controlled type 1 diabetes mellitus.
AB  - To investigate the hypothesis that diabetes induces nephrogenic diabetes
      insipidus, we studied the urine-concentrating ability in response to vasopressin
      (AVP) in 12 patients with insulin-dependent diabetes mellitus (IDDM) and 12
      nondiabetic controls. Subjects were euglycemic-clamped, and after oral water
      loading, AVP was infused intravenously for 150 min. AVP induced a greater
      (P<0.001) rise in urine osmolality in controls (67.6+/-10.7 to 720+/-31.1
      mosmol/kg, P<0.001) than in IDDM patients (64.3+/-21.6 to 516.7+/-89.3 mosmol/kg,
      P<0.001). Urinary aquaporin-2 concentrations after AVP infusion were higher in
      controls (611.8+/-105.6 fmol/mg creatinine) than in IDDM (462.0+/-94.9 fmol/mg
      creatinine, P = 0. 003). Maximum urine osmolality in IDDM was inversely related
      to chronic blood glucose control, as indicated by Hb A(Ic) (r = -0.87, P =
      0.002). To test the hypothesis that improved glycemic control could reverse
      resistance to AVP, 10 IDDM subjects with poor glycemic control (Hb A(Ic) >9%)
      were studied before (B) and after (A) intensified glycemic control. Maximum urine
      osmolality in response to AVP increased with improved glycemic control (B,
      443.8+/-49.0; A, 640.0+/-137.2 mosmol/kg, P<0.001), and urinary aquaporin-2
      concentrations after AVP increased from 112.7 +/-69 to 375+/-280 fmol/mg
      creatinine (P = 0.006), with improved glycemic control. Poorly controlled IDDM is
      associated with reversible renal resistance to AVP.

PMID- 10893336
TI  - Compartmental modeling of postprandial dietary nitrogen distribution in humans.
AB  - A linear 11-compartment model was developed to describe and simulate the
      postprandial distribution of dietary nitrogen. The values of its 15 constant
      diffusion coefficients were estimated from the experimental measurement of (15)N
      nitrogen kinetics in the intestine, blood, and urine after the oral
      administration of (15)N-labeled milk protein in humans. Model structure
      development, parameter estimation, and sensibility analysis were achieved using
      SAAM II and SIMUSOLV softwares. The model was validated at each stage of its
      development by testing successively its a priori and a posteriori
      identifiability. The model predicted that, 8 h after a meal, the dietary nitrogen
      retained in the body comprised 28% free amino acids and 72% protein,
      approximately 30% being recovered in the splanchnic bed vs. 70% in the peripheral
      area. Twelve hours after the meal, these values had decreased to 18 and 23% for
      the free amino acid fraction and splanchnic nitrogen, respectively. Such a model
      constitutes a useful, explanatory tool to describe the processes involved in the
      metabolic utilization of dietary proteins.

PMID- 10893337
TI  - Mechanism of coronary vasodilation to insulin and insulin-like growth factor I is
      dependent on vessel size.
AB  - Insulin and insulin-like growth factor I (IGF-I) influence numerous metabolic and
      mitogenic processes; these hormones also have vasoactive properties. This study
      examined mechanisms involved in insulin- and IGF-I-induced dilation in canine
      conduit and microvascular coronary segments. Tension of coronary artery segments
      was measured after constriction with PGF(2alpha). Internal diameter of coronary
      microvessels (resting diameter = 112.6+/-10.1 microm) was measured after
      endothelin constriction. Vessels were incubated in control (Krebs) solution and
      were treated with N(omega)-nitro-L-arginine (L-NA), indomethacin, or K(+) channel
      inhibitors. After constriction, cumulative doses of insulin or IGF-I (0.1-100
      ng/ml) were administered. In conduit arteries, insulin produced modest maximal
      relaxation (32 +/- 5%) compared with IGF-I (66+/-12%). Vasodilation was
      attenuated by nitric oxide synthase (NOS) and cyclooxygenase inhibition and was
      blocked with KCl constriction. Coronary microvascular relaxation to insulin and
      IGF-I was not altered by L-NA, indomethacin, tetraethylammonium chloride,
      glibenclamide, charybdotoxin, and apamin; however, tetrabutylammonium chloride
      attenuated the response. In conclusion, insulin and IGF-I cause vasodilation in
      canine coronary conduit arteries and microvessels. In conduit vessels,
      NOS/cyclooxygenase pathways are involved in the vasodilation. In microvessels,
      relaxation to insulin and IGF-I is not mediated by NOS/cyclooxygenase pathways
      but rather through K(+)-dependent mechanisms.

PMID- 10893338
TI  - Insulin stimulation of muscle protein synthesis in obese Zucker rats is not via a
      rapamycin-sensitive pathway.
AB  - The obese Zucker rat is resistant to insulin for glucose disposal, but it is
      unknown whether this insulin resistance is accompanied by alterations of insulin
      mediated muscle protein synthesis. We examined rates of muscle protein synthesis
      either with or without insulin in lean and obese Zucker rats with the use of a
      bilateral hindlimb preparation. Additional experiments examined insulin's effect
      on protein synthesis with or without rapamycin, an inhibitor of protein
      synthesis. Protein synthesis in red and white gastrocnemius was stimulated by
      insulin compared with control (no insulin) in obese (n = 10, P<0.05) but not in
      lean (n = 10, P>0.05) Zucker rats. In white gastrocnemius, rapamycin
      significantly reduced rates of protein synthesis compared with control in lean (n
      = 6) and obese (n = 6) rats; however, in red gastrocnemius, the attenuating
      effect of rapamycin occurred only in obese rats. The addition of insulin to
      rapamycin resulted in rates of synthesis that were similar to those for rapamycin
      alone for lean rats and to those for insulin alone (augmented) for obese rats in
      both tissues. Our results demonstrate that insulin enhances protein synthesis in
      muscle that is otherwise characterized as insulin resistant. Furthermore,
      rapamycin inhibits protein synthesis in muscle of obese Zucker rats; however,
      stimulation of protein synthesis by insulin is not via a rapamycin-sensitive
      pathway.

PMID- 10893339
TI  - Amelioration of denervation-induced atrophy by clenbuterol is associated with
      increased PKC-alpha activity.
AB  - Rat soleus muscle was denervated for 3 or 7 days, and total membrane protein
      kinase C (PKC) activity and translocation and immunocytochemical localization of
      PKC isoforms were examined. Dietary administration of clenbuterol concomitant
      with denervation ameliorated the atrophic response and was associated with
      increased membrane PKC activity at both 3 (140%) and 7 (190%) days. Of the five
      PKC isoforms (alpha, epsilon, theta, zeta, and mu) detected in soleus muscle by
      Western immunoblotting, clenbuterol treatment affected only the PKC-alpha and PKC
      theta forms. PKC-alpha was translocated to the membrane fraction upon
      denervation, and the presence of clenbuterol increased membrane-bound PKC-alpha
      and active PKC-alpha as assayed by Ser(657) phosphorylation. PKC-theta protein
      was downregulated upon denervation, and treatment with clenbuterol further
      decreased both cytosolic and membrane levels. Immunolocalization of PKC-theta
      showed differences for regulatory and catalytic domains, with the latter showing
      fast-fiber type specificity. The results suggest potential roles of PKC-alpha and
      PKC-theta in the mechanism of action of clenbuterol in alleviating denervation
      induced atrophy.

PMID- 10893340
TI  - Cytokines and endotoxin induce cytokine receptors in skeletal muscle.
AB  - Proinflammatory cytokines are important factors in the regulation of diverse
      aspects of skeletal muscle function; however, the muscle cytokine receptors
      mediating these functions are uncharacterized. Binding kinetics (dissociation
      constant = 39+/-4.7 x 10(-9) M, maximal binding = 3.5+/-0.23 x 10(-12) mol/mg
      membrane protein) of muscle tumor necrosis factor (TNF) receptors were obtained.
      Skeletal muscle was found to express mRNAs encoding interleukin-1 type I and II
      receptors, interleukin-6 receptor (IL-6R), and interferon-gamma receptor by RT
      PCR, but these receptors were below limits of detection of ligand-binding assay
      (> or =1 fmol binding sites/mg protein). Twenty-four hours after intraperitoneal
      administration of endotoxin to rats, TNF receptor type II (TNFRII) and IL-6R mRNA
      were increased in skeletal muscle (P<0.05). In cultured L6 cells, the expression
      of mRNA encoding TNFRII and IL-6R receptors was induced by TNF-alpha, and all six
      cytokine receptor mRNA were induced by a mixture of TNF-alpha, IFN-gamma, and
      endotoxin (P<0.05). This suggests that the low level of cytokine receptor
      expression is complemented by a capacity for receptor induction, providing a
      clear mechanism for amplification of cytokine responses at the muscle level.

PMID- 10893341
TI  - Muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase
      in human skeletal muscle.
AB  - Physiological stress associated with muscle damage results in systemic insulin
      resistance. However, the mechanisms responsible for the insulin resistance are
      not known; therefore, the present study was conducted to elucidate the molecular
      mechanisms associated with insulin resistance after muscle damage. Muscle
      biopsies were obtained before (base) and at 1 h during a hyperinsulinemic
      euglycemic clamp (40 mU x kg(-1) x min(-1)) in eight young (age 24+/-1 yr)
      healthy sedentary (maximal O(2) consumption, 49.7+/-2.4 ml x kg(-1) x min(-1))
      males before and 24 h after eccentric exercise (ECC)-induced muscle damage. To
      determine the role of cytokines in ECC-induced insulin resistance, venous blood
      samples were obtained before (control) and 24 h after ECC to evaluate ex vivo
      endotoxin-induced mononuclear cell secretion of tumor necrosis factor (TNF)
      alpha, interleukin (IL)-6, and IL-1beta. Glucose disposal was 19% lower after ECC
      (P<0.05). Insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine
      phosphorylation was 45% lower after ECC (P<0.05). Insulin-stimulated
      phosphatidylinositol (PI) 3-kinase, Akt (protein kinase B) serine
      phosphorylation, and Akt activity were reduced 34, 65, and 20%, respectively,
      after ECC (P < 0.05). TNF-alpha, but not IL-6 or IL-1beta production, increased
      2.4-fold 24 h after ECC (P<0.05). TNF-alpha production was positively correlated
      with reduced insulin action on PI 3-kinase (r = 0.77, P = 0.04). In summary, the
      physiological stress associated with muscle damage impairs insulin stimulation of
      IRS-1, PI 3-kinase, and Akt-kinase, presumably leading to decreased insulin
      mediated glucose uptake. Although more research is needed on the potential role
      for TNF-alpha inhibition of insulin action, elevated TNF-alpha production after
      muscle damage may impair insulin signal transduction.

PMID- 10893342
TI  - Inhibitory effect of NF-kappaB on 1,25-dihydroxyvitamin D(3) and retinoid X
      receptor function.
AB  - Responsiveness to 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] may be diminished
      in osteoporosis and inflammatory arthritis. The inflammatory cytokine tumor
      necrosis factor-alpha (TNF-alpha) is produced in excess in these disorders and
      has been shown to decrease osteoblast transcriptional responsiveness to vitamin D
      and to inhibit the binding of the vitamin D receptor (VDR) and its nuclear
      partner the retinoid X receptor (RXR) to DNA. Previous studies have shown that a
      vitamin D (VDRE) or retinoid X DNA response element (RXRE) is sufficient to
      confer TNF-alpha inhibition of vitamin D or retinoid-stimulated transcription in
      the absence of known TNF-alpha-responsive DNA sequences. We tested the hypothesis
      that the TNF-alpha-stimulated transcription factor nuclear factor (NF)-kappaB
      could, in part, mediate TNF-alpha action by inhibiting the transcriptional
      potency of the VDR and RXR at their cognate cis regulatory sites. Osteoblastic
      ROS 17/2.8 cells transfected with a dose of NF-kappaB comparable to that
      stimulated by TNF-alpha decreased 1,25(OH)(2)D(3)-stimulated transcription. This
      inhibitory effect of NF-kappaB was not observed on basal transcription of a
      heterologous reporter in the absence of the VDRE. The effects of NF-kappaB and
      TNF-alpha were comparable but not additive. COS-7 cells were cotransfected with
      reporters under the regulation of VDRE or RXRE along with vectors expressing VDR,
      RXR, and NF-kappaB nuclear proteins. Reconstituted NF-kappaB and the NF-kappaB
      subunit p65 alone, but not p50, dose dependently suppressed basal and ligand
      stimulated transcription. p65 overexpression completely abrogated enhanced VDRE
      mediated transcriptional activity in response to 1,25(OH)(2)D(3). Electrophoretic
      mobility shift experiments did not reveal a direct effect of recombinant NF
      kappaB or its individual subunits on the binding of heterodimeric VDR-RXR to DNA.
      These results suggest that TNF-alpha inhibition of hormone-stimulated
      transcriptional activation may be mediated by activation of NF-kappaB. In
      contrast, the inhibitory effect of TNF-alpha on binding of receptors to DNA is
      unlikely to be mediated by NF-kappaB and is not necessary for inhibition of
      transcription.

PMID- 10893343
TI  - Fatty acid cycling in the fasting rat.
AB  - Adipose tissue lipolysis and fatty acid reesterification by liver and adipose
      tissue were investigated in rats fasted for 15 h under basal and calorigenic
      conditions. The fatty acid flux initiated by adipose fat lipolysis in the fasted
      rat is mostly futile and is characterized by reesterification of 57% of lipolyzed
      free fatty acid (FFA) back into adipose triglycerides (TG). About two-thirds of
      FFA reesterification are carried out before FFA release into plasma, whereas the
      rest consists of plasma FFA extracted by adipose tissue. Thirty-six percent of
      the fasting lipolytic flux is accounted for by oxidation of plasma FFA, whereas
      only a minor fraction is channeled into hepatic very low density lipoprotein
      triglycerides (VLDL-TG). Total body calorigenesis induced by thyroid hormone
      treatment and liver-specific calorigenesis induced by treatment with beta, beta'
      tetramethylhexadecanedioic acid (Medica 16) are characterized by a 1.7- and 1.3
      fold increase in FFA oxidation, respectively, maintained by a 1.5-fold increase
      in adipose fat lipolysis. Hepatic reesterification of plasma FFA into VLDL-TG is
      negligible under both calorigenic conditions. Hence, total body fatty acid
      metabolism is regulated by adipose tissue as both source and sink. The futile
      nature of fatty acid cycling allows for its fine tuning in response to metabolic
      demands.

PMID- 10893344
TI  - Direct measurement of the lumped constant for 2-deoxy-[1-(14)C]glucose in vivo in
      human skeletal muscle.
AB  - The lumped constant (LC) is used to convert the clearance rate of 2-deoxy-D
      glucose (2-DG(CR)) to that of glucose (Glc(CR)). There are currently no data to
      validate the widely used assumption of an LC of 1.0 for human skeletal muscle. We
      determined the LC for 2-deoxy-[1-(14)C]glucose (2-DG) in 18 normal male subjects
      (age, 29+/- 2 yr; body mass index, 24.8+/-0.8 kg/m(2)) after an overnight fast
      and during physiological (1 mU x kg(-1) x min(-1) insulin infusion for 180 min)
      and supraphysiological (5 mU x kg(-1) x min(-1) insulin infusion for 180 min)
      hyperinsulinemic conditions. Normoglycemia was maintained with the euglycemic
      clamp technique. The LC was measured directly with the use of a novel triple
      tracer-based method. [3-(3)H]glucose, 2-[1-(14)C]DG, and [(12)C]mannitol (Man)
      were injected as a bolus into the brachial artery. The concentrations of [3
      (3)H]glucose and 2-[1-(14)C]DG (dpm/ml plasma) and of Man (micromol/l) were
      determined in 50 blood samples withdrawn from the ipsilateral deep forearm vein
      over 15 min after the bolus injection. The LC was calculated by a formula
      involving blood flow calculated from Man and the Glc(CR) and 2-DG(CR). The LC
      averaged 1.26+/-0.08 (range 1.06-1.43), 1.15+/-0.05 (0.99-1.39), and 1.18+/-0.05
      (0.97-1.37) under fasting conditions and during the 1 and 5 mU x kg(-1). min(-1)
      insulin infusions (not significant between the different insulin concentrations,
      mean LC = 1.2, P<0.01 vs. 1.0). We conclude that, in normal subjects, the LC for
      2-DG in human skeletal muscle is constant over a wide range of insulin
      concentrations and averages 1. 2.

PMID- 10893345
TI  - Too many journals, too little time.

PMID- 10893346
TI  - Cirrhotic hydrothorax and the "Law of unintended consequences".

PMID- 10893347
TI  - Dilemmas and realities of rapid diagnostic tests for tuberculosis.

PMID- 10893348
TI  - Exertional dyspnea in congestive heart failure. Living longer and doing more?

PMID- 10893349
TI  - Allergic bronchopulmonary aspergillosis.

PMID- 10893350
TI  - A disease called asthma.

PMID- 10893351
TI  - Empiric antibiotic use and resistant microbes. A "catch-22" for the 21st century.

PMID- 10893352
TI  - Thoracoscopy and talc poudrage in the management of hepatic hydrothorax.
AB  - STUDY OBJECTIVE: To determine indications, limitations, morbidity and mortality
      of surgical thoracoscopy for management of hepatic hydrothorax, a rare, but often
      recurrent, complication in cirrhotic patients. PATIENTS AND METHODS: From May
      1985 through May 1999, 10 men and 8 women, with a mean age of 57.6 years (range,
      26 to 76 years), underwent 21 therapeutic thoracoscopies to achieve pleurodesis
      by application of talc. RESULTS: The procedure was effective in 10 of 21
      procedures. There were four recurrences (19. 1%) that were retreated, with only
      one being successful. In this specific group, we detected high morbidity (57.1%)
      and mortality (38.9%) during the follow-up period of 3 months. Diaphragmatic
      defects were localized and closed five times (23.8%). Hospital stay was
      approximately 15 days (range, 5 to 41 days). CONCLUSION: The procedure appears to
      be indicated for these fragile patients, especially when medical therapy fails.
      Immediate efficacy was 47.6%, increasing to 60% with videothoracoscopy and suture
      of the diaphragmatic defect. However, morbidity and mortality were high.

PMID- 10893353
TI  - Negative pressure ventilation vs external high-frequency oscillation during rigid
      bronchoscopy. A controlled randomized trial.
AB  - STUDY OBJECTIVES: To compare the effectiveness of two modalities of external
      ventilation during rigid bronchoscopy: intermittent negative pressure ventilation
      (INPV) and external high-frequency oscillation (EHFO). DESIGN: Prospective,
      controlled, randomized, nonblinded study. SETTING: University-affiliated
      hospital. PATIENTS: Seventy patients undergoing interventional rigid bronchoscopy
      for tracheobronchial lesions were enrolled into the study. INTERVENTIONS:
      Mechanical ventilation was performed by INPV or EHFO. When pulse oximetry was <
      90%, manually assisted ventilation was delivered. MEASUREMENTS AND RESULTS:
      Arterial blood gases were sampled preoperatively and intraoperatively. Most
      patients in both groups had normal intraoperative PaCO(2) (mean, 43. 6 +/- 11.8
      mm Hg under EHFO and 37.4 +/- 8.2 mm Hg under INPV; p = 0.012), and acidemia
      occurred in 9 of 35 patients of EHFO group and in 2 of 35 patients of INPV group
      (p = 0.049). Hypercapnia (PaCO(2) > 50 mm Hg) was observed in 10 patients under
      EHFO and in 2 with INPV (p = 0.026). Intraoperative mean PaO(2) was similar
      (101.4 +/- 52.9 mm Hg with EHFO and 124.2 +/- 50.3 mm Hg with INPV; p = 0.07),
      but O(2) supply was different (3.5 +/- 2.3 L/min during INPV and 8.5 +/- 6.2
      L/min during EHFO; p < 0.001). Intraoperative hypoxemia (PaO(2) < 60 mm Hg)
      occurred in five patients with EHFO and two with INPV (p = 0.426). Three EHFO
      patients required manually assisted ventilation (mean, 0.2 +/- 0.9), but no INPV
      patient did (p = 0.142). CONCLUSIONS: External negative pressure ventilation
      appears to be a suitable choice during rigid bronchoscopy: both EHFO and INPV
      ensure effective ventilation and comfortable operating conditions in the majority
      of patients. Some patients may receive inadequate ventilation with EHFO,
      developing respiratory acidosis and requiring manually assisted ventilation. In
      comparison with INPV, EHFO requires a higher fraction of inspired oxygen.

PMID- 10893354
TI  - Thoracoscopic decortication as first-line therapy for pediatric parapneumonic
      empyema. A case series.
AB  - STUDY OBJECTIVES: Previous articles have promoted the early use of thoracotomy
      and decortication for refractory empyema. This study examines thoracoscopy and
      decortication at the time of initial chest tube placement in pediatric patients
      with parapneumonic empyema. DESIGN: We reviewed the medical records of 16
      consecutive patients who were children with parapneumonic empyema. RESULTS:
      Thirteen children (group 1) underwent thoracoscopic decortication and tube
      thoracostomy as their initial operative procedures; 3 children (group 2) had tube
      thoracostomy alone. In both groups, chest tubes were removed prior to their
      discharge to home. The mean (+/- SD) operative time for thoracoscopy was 81 +/-
      19 min with no complications. On average, chest tubes were removed by
      postoperative day 4. The mean time to discharge was 8.3 days. Two children
      eventually required lobectomy. The mean operative time for chest tube placement
      alone was 21 +/- 3 min. Children required chest tube drainage for an average of
      12.3 days. The mean time to discharge was 16.6 days. Two patients required a
      total of five additional operative procedures, including two additional chest
      tube placements, two open decortications, and one lobectomy. CONCLUSIONS:
      Thoracoscopic decortication is effective in the early treatment of pediatric
      parapneumonic empyema. It facilitates visualization, evacuation, and mechanical
      decortication of the pleural space with no additional morbidity and may lead to
      reduced time for chest tube drainage, shorter hospitalization, and more rapid
      clinical recovery.

PMID- 10893355
TI  - Predicting culture results for Mycobacterium tuberculosis complex. Amplified
      mycobacterium tuberculosis direct test and acid-fast bacilli microscopy.
AB  - STUDY OBJECTIVE: To evaluate the usefulness of the Gen-Probe Amplified
      Mycobacterium Tuberculosis Direct Test (AMTDT; Gen-Probe; San Diego, CA) in
      predicting the results of cultures in routine laboratory analysis of a patient
      population with a high incidence of tuberculosis (TB). PATIENTS: Three hundred
      ten patients suspected of pulmonary mycobacterial infection or receiving
      antituberculous chemotherapy, accrued between 1996 and 1997. SETTING: Tertiary
      care facility located in Northern Italy. DESIGN: We retrospectively compared the
      AMTDT results with the results of cultures. AMTDT results were also compared with
      those of acid-fast bacilli (AFB) staining of the same specimens. The study
      included 360 respiratory specimens from 310 patients collected between 1996 and
      1997. In 1996, we used the initial version of AMTDT (50 microL of sediment); in
      1997, we used the new version of AMTDT (450 microL of sediment). RESULTS:
      Compared with cultures, AMTDT and AFB staining had sensitivities of 87.2% and
      68.4%, and specificities of 70.0% and 89.7%, respectively. When AMTDT and AFB
      staining were both positive, the sensitivity and specificity were 89.3% and
      96.9%, respectively. When AMTDT and AFB staining were in disagreement, the
      sensitivity and specificity of AMTDT were 81.8% and 18.1%, respectively.
      CONCLUSION: We conclude that when AMTDT is used to predict culture outcome, the
      results should be evaluated in conjunction with AFB staining results before
      making decisions about TB management.

PMID- 10893356
TI  - Chest radiographs in acute pulmonary embolism. Results from the International
      Cooperative Pulmonary Embolism Registry.
AB  - OBJECTIVES: To characterize chest radiographic interpretations in a large
      population of patients who have received a diagnosis of acute pulmonary embolism
      and to estimate the sensitivity and specificity of chest radiographic
      abnormalities for right ventricular hypokinesis that has been diagnosed by
      echocardiography. DESIGN: A prospective observational study at 52 hospitals in
      seven countries. PATIENTS: A total of 2,454 consecutive patients who had received
      a diagnosis of acute pulmonary embolism between January 1995 and November 1996.
      RESULTS: Chest radiographs were available for 2,322 patients (95%). The most
      common chest radiographic interpretations were cardiac enlargement (27%), normal
      (24%), pleural effusion (23%), elevated hemidiaphragm (20%), pulmonary artery
      enlargement (19%), atelectasis (18%), and parenchymal pulmonary infiltrates
      (17%). The results of chest radiographs were abnormal for 509 of 655 patients
      (78%) who had undergone a major surgical procedure within 2 months of the
      diagnosis of pulmonary embolism: normal results for chest radiograph often
      accompanied pulmonary embolism after genitourinary procedures (37%), orthopedic
      surgery (29%), or gynecologic surgery (28%), whereas they rarely accompanied
      pulmonary emboli associated with thoracic procedures (4%). Chest radiographs were
      interpreted to show cardiac enlargement for 149 of 309 patients with right
      ventricular hypokinesis that was detected by echocardiography (sensitivity, 0.48)
      and for 178 of 485 patients without right ventricular hypokinesis (specificity,
      0.63). Chest radiographs were interpreted to show pulmonary artery enlargement
      for 118 of 309 patients with right ventricular hypokinesis (sensitivity, 0.38)
      and for 117 of 483 patients without right ventricular hypokinesis (specificity,
      0.76). CONCLUSIONS: Cardiomegaly is the most common chest radiographic
      abnormality associated with acute pulmonary embolism. Neither pulmonary artery
      enlargement nor cardiomegaly appears sensitive or specific for the
      echocardiographic finding of right ventricular hypokinesis, an important
      predictor of mortality associated with acute pulmonary embolism.

PMID- 10893357
TI  - Effects of nitric oxide inhalation after pulmonary thromboendarterectomy for
      chronic pulmonary thromboembolism.
AB  - STUDY OBJECTIVES: To examine the hypothesis that nitric oxide (NO) inhalation
      improves hemodynamics and gas exchange in patients with chronic pulmonary
      thromboembolism after pulmonary thromboendarterectomy. DESIGN: Prospective
      crossover clinical study. SETTING: : Surgical ICU in a national education and
      research hospital. PATIENTS: : Seven patients (mean age +/- SD, 54 +/- 11 years)
      who underwent elective pulmonary thromboendarterectomy for chronic pulmonary
      thromboembolism. INTERVENTIONS: Patients breathed 20 parts per million of NO gas
      for 30 min at 12-h intervals until extubation of the trachea. MEASUREMENTS AND
      RESULTS: Hemodynamics and arterial blood gas levels were analyzed before, during,
      and after NO inhalation. Waveform of pulmonary artery pressure (PAP) was
      evaluated using fractional pulse pressure (PPf): (systolic PAP - diastolic
      PAP)/mean PAP. After surgery, pulmonary vascular resistance decreased, PPf
      decreased, and cardiac index increased significantly. At the first trial, NO
      inhalation resulted in a slight improvement in arterial oxygen tension (from 173
      +/- 33 to 196 +/- 44 mm Hg; p < 0.05), while hemodynamics did not change
      significantly. Twelve hours later, NO inhalation decreased pulmonary vascular
      resistance index (from 312 +/- 98 to 277 +/- 93 dyne.s. cm(-5)/m(2); p < 0.01),
      while the change in oxygenation was not significant. CONCLUSIONS: Immediately
      after pulmonary thromboendarterectomy for chronic pulmonary thromboembolism, NO
      inhalation improved oxygenation; at 12 h after surgery, NO inhalation resulted in
      decreased pulmonary vascular resistance, although both changes were small.

PMID- 10893358
TI  - Plasma vascular endothelial growth factor in acute mountain sickness.
AB  - STUDY OBJECTIVES: To investigate the hypothesis that an increase in circulating
      vascular endothelial growth factor (VEGF) occurs in mountaineers at high
      altitude, particularly in association with acute mountain sickness (AMS) and/or
      low hemoglobin oxygen saturation. DESIGN: : Collection of medical histories, AMS
      scores, plasma samples, and arterial oxygen saturation (SaO(2)) measurements from
      mountaineers at 1,500 feet (sea level) and at 14,200 feet. SETTING: Mount
      McKinley ("Denali"), AK. PARTICIPANTS: Sixty-six mountaineers. INTERVENTIONS:
      None. MEASUREMENTS AND RESULTS: Plasma VEGF at 14,200 feet was not increased in
      any group. In fact, plasma VEGF was significantly lower in subjects who did not
      develop AMS (53 +/- 7.9 pg/mL; mean +/- SEM; n = 47) compared to control subjects
      at sea level (98.4 +/- 14.3 pg/mL; n = 7; p = 0.005). Plasma VEGF at 14, 200 feet
      for subjects with AMS (62 +/- 12 pg/mL; n = 15) did not differ significantly from
      subjects at 14,200 feet without AMS, or from control subjects at sea level. Of a
      small number of subjects with paired specimens at sea level and at base camp (n =
      5), subjects who exhibited a decrease in plasma VEGF at 14,200 feet were those
      who did not develop AMS. Neither SaO(2), prior AMS, AMS symptom scores, or
      acetazolamide use were correlated with plasma VEGF. CONCLUSIONS: Subjects at high
      altitude who do not develop AMS have lower plasma VEGF levels compared to control
      subjects at sea level. Plasma VEGF at high altitude is not elevated in
      association with AMS or hypoxia. Sustained plasma VEGF at altitude may reflect a
      phenotype more susceptible to AMS.

PMID- 10893359
TI  - Role of respiratory function in exercise limitation in chronic heart failure.
AB  - OBJECTIVE: To test the hypothesis that respiratory function contributes to limit
      maximal exercise performance in patients with chronic heart failure by using the
      technique of dead space loading during exercise. DESIGN: Blinded subjects
      underwent two maximal incremental exercise tests in random order on an upright
      bicycle ergometer: one with and one without added dead space. SETTING: : Tertiary
      care university teaching hospital. SUBJECTS: Seven patients with stable chronic
      heart failure (mean +/- SEM left ventricular ejection fraction, 27 +/- 3%).
      RESULTS: Subjects were able to significantly increase their peak minute
      ventilation during exercise with added dead space when compared with control
      exercise (57.4 +/- 5.9 vs 50.0 +/- 5.6 L/min; p < 0.05). Peak oxygen uptake,
      workload, heart rate, and exercise duration were not significantly different
      between the added dead space and control tests. Breathing pattern was
      significantly deeper and slower at matched levels of ventilation during exercise
      with added dead space. CONCLUSION: Because patients with chronic heart failure
      had significant ventilatory reserve at the end of exercise and were able to
      further increase their maximal minute ventilation, we conclude that respiratory
      function does not contribute to limitation of exercise in patients with chronic
      heart failure.

PMID- 10893360
TI  - Maximum insufflation capacity.
AB  - OBJECTIVE: To investigate the effect of deep lung insufflations on maximum
      insufflation capacities (MICs) and peak cough flows (PCFs) for patients with
      neuromuscular disease. METHOD: Forty-three patients with neuromuscular disease
      were trained in stacking delivered volumes of air to deep lung insufflation and
      were prescribed a program of air stacking once their vital capacities (VCs) were
      noted to be < 2,000 mL. VC, MIC, and unassisted and assisted PCF were monitored.
      The initial data were compared with the highest MICs subsequently achieved. For
      those patients whose MICs only decreased, we compared the initial data with the
      most recent data. RESULTS: The MICs increased from (mean +/- SD) 1,402 +/- 530 mL
      to 1,711 +/- 599 mL (p < 0.001) for 30 patients and only decreased for 13
      patients. Patients for whom the MICs increased also had a significant increase in
      assisted PCF from 3.7 +/- 1.4 to 4.3 +/- 1.6 L/s (p < 0.05) despite having
      somewhat decreasing VCs and unassisted PCFs. CONCLUSION: With training, the
      capacity to stack air to deep insufflations can improve despite progressive
      neuromuscular disease. This can result in increased cough effectiveness.

PMID- 10893361
TI  - Allergic bronchopulmonary aspergillosis in the asthma clinic. A prospective
      evaluation of CT in the diagnostic algorithm.
AB  - OBJECTIVE: Allergic bronchopulmonary aspergillosis (ABPA) occurs in cases of
      atopic asthma and may result in important lung disease. Early diagnosis is
      essential as this disease is responsive to steroids. However, while asthma is
      common, ABPA is infrequently diagnosed. CT allows precision in the diagnosis of
      central bronchiectasis (which is virtually pathognomonic of ABPA) and may enable
      earlier diagnosis. DESIGN: A prospective evaluation of 255 patients with asthma
      for ABPA, using skin prick testing (SPT) for Aspergillus fumigatus (AF) as a
      screening tool and incorporating CT into the diagnostic algorithm. SETTING:
      Asthma clinic, Green Lane Hospital, Auckland, New Zealand. PARTICIPANTS: Patients
      with asthma. INTERVENTIONS: ABPA was diagnosed using "essential" criteria (ie,
      asthma, SPT positivity to AF, elevated serum total IgE, elevated serum AF
      specific IgE, and pulmonary infiltrates seen on chest radiography or central
      bronchiectasis seen on CT scan) and "minimal essential" criteria (ie, asthma, SPT
      positivity, and central bronchiectasis). MEASUREMENTS AND RESULTS: Two hundred
      fifty-five consecutive patients with asthma who consented to SPT were studied:
      218 of 255 patients (86.8%) were atopic; and 47 of 255 patients (21.6%) were AF
      positive, of whom 35 accepted further evaluation including CT scanning. A secure
      diagnosis of ABPA, satisfying all essential criteria, was evident in 9 of 35
      patients (25.7%), a proportion that increased to 13 of 35 patients (37.1%) by
      using the minimal essential diagnostic criteria. CONCLUSIONS: SPT positivity to
      AF was present in approximately 20% of patients in the asthma clinic. A diagnosis
      of ABPA is disclosed by CT in 25 to 40% of SPT-positive patients, depending on
      the selection of diagnostic criteria. These findings support the use of SPT as a
      screening tool in the asthma clinic and indicate that a routine CT scan is
      warranted in SPT-positive patients.

PMID- 10893362
TI  - Effect of a thromboxane A(2) antagonist on sputum production and its
      physicochemical properties in patients with mild to moderate asthma.
AB  - STUDY OBJECTIVE: To determine the effects of a specific thromboxane A(2) (TxA(2))
      receptor antagonist, seratrodast, on asthma control and airway secretions.
      DESIGN: Multicenter, double-blind, randomized, placebo-controlled study.
      PATIENTS: Forty-five patients with mild to moderate asthma who had been
      continuously expectorating sputum of > 20 g/d. Patients with a current pulmonary
      infection or taking oral corticosteroids, antibiotics, or mucolytic agents were
      excluded from the trial. INTERVENTIONS: Following a 2-week run-in period, while
      pulmonary function, sputum production, and mucociliary function were assessed,
      patients were assigned to receive seratrodast, 40 mg/d, or placebo for 6 weeks.
      MEASUREMENTS AND RESULTS: During the treatment period, the changes in FEV(1) and
      peak expiratory flow (PEF) were not different between the two patient groups, but
      there were significant reductions in diurnal variation of PEF (p = 0.034),
      frequency of daytime asthma symptoms (p = 0.030), and daytime supplemental use of
      beta(2)-agonist (p = 0.032) in the seratrodast group. For sputum analysis,
      seratrodast treatment decreased the amount of sputum (p = 0.005), dynamic
      viscosity (p = 0. 007), and albumin concentration (p = 0.028), whereas it had no
      effect on elastic modulus or fucose concentration. Nasal clearance time of a
      saccharin particle was shortened in the seratrodast group at week 4 (p = 0.031)
      and week 6 (p = 0.025), compared with the placebo group. CONCLUSION: Blockade of
      TxA(2) receptor has minimal effects on pulmonary function, but may cause an
      improvement in mucociliary clearance by decreasing the viscosity of airway
      secretions.

PMID- 10893363
TI  - Cystic fibrosis. End-stage care in Canada.
AB  - OBJECTIVES: To determine the circumstances in which individuals with cystic
      fibrosis (CF) die, the role of different caregivers, and the extent of palliative
      care for CF patients. DESIGN: Mailed survey of CF physicians. SETTING: CF centers
      in Canada. PATIENTS: All CF deaths in 1996 known to centers in Canada. RESULTS:
      The mean age (+/- SD) at death of the 45 individuals included in the study was
      25.8 +/- 13.5 years. The major cause of death was respiratory (34 patients;
      75.5%). Nutritional concerns were common. Lung transplantation was considered in
      42 patients (93.2%), with 7 patients (17.1%) being entered on a list, but it was
      carried out in only 2 patients (4.4%). Autopsies were performed on only 10
      patients (22.2%). Most patients died in hospital (37 patients; 82.2%), and 7
      patients (15.6%) died in ICUs while receiving intermittent positive-pressure
      ventilation. Palliative care was never discussed in 10 patients (25%). In a
      further 16 patients (40%), it was not discussed until the last month before
      death. CONCLUSIONS: Respiratory disease remains the most common cause of death in
      CF patients. Lung transplantation is frequently considered, but most patients die
      without having had a transplant. Discussions on end-of-life care could be
      considered sooner.

PMID- 10893364
TI  - Pregnancy in cystic fibrosis. Fetal and maternal outcome.
AB  - OBJECTIVE: To assess the effect of pregnancy on pulmonary function and survival
      in women with cystic fibrosis (CF) and to assess the fetal outcome. DESIGN:
      Cohort study. The data analyzed were collected from the Toronto CF database,
      chart review, and patient questionnaire. SETTING: Tertiary-care center. PATIENTS:
      All women with CF who, at the time of diagnosis or pregnancy, attended the
      Toronto Cystic Fibrosis Clinics between 1961 and 1998. RESULTS: From 1963 to
      1998, there were 92 pregnancies in 54 women. There were 11 miscarriages and 7
      therapeutic abortions. Forty-nine women gave birth to 74 children. The mean
      follow-up time was 11 +/- 8 years. One patient was lost to follow-up shortly
      after delivery, and one was lost after 12 years. The overall mortality rate was
      19% (9 of 48 patients). Absence of Burkholderia cepacia (p < 0.001), pancreatic
      sufficiency (p = 0.01), and prepregnancy FEV(1) > 50% predicted (p = 0.03) were
      associated with better survival rates. When adjusted for the same parameters,
      pregnancy did not affect survival compared to the entire adult female CF
      population. The decline in FEV(1) was comparable to that in the total CF
      population. Three women had diabetes mellitus, and seven developed gestational
      diabetes. There were six preterm infants and one neonatal death. CF was diagnosed
      in two children. CONCLUSIONS: The maternal and fetal outcome is good for most
      women with CF. Risk factors for mortality are similar to those for the
      nonpregnant CF population. Pregnancies should be planned so that there is
      opportunity for counseling and optimization of the medical condition. Good
      communication between the CF team and the obstetrician is important.

PMID- 10893365
TI  - Validation of an instrument measuring patient satisfaction with chest
      physiotherapy techniques in cystic fibrosis.
AB  - OBJECTIVES: Chest physiotherapy (CPT) has been an important part of cystic
      fibrosis (CF) treatment regimens for > 40 years. Techniques with different
      perceived costs, benefits, and patient satisfaction exist. An instrument
      measuring patient satisfaction with CPT has not been reported. Our goal was to
      develop and validate such an instrument. DESIGN: A cross-sectional survey sent to
      349 patients seen at a large, urban, academic CF care center. The two-page survey
      asked 17 questions related to CPT satisfaction (efficacy, convenience, comfort,
      overall satisfaction), followed by 4 general CF-care questions (disease severity,
      importance of therapies, prescribed vs missed therapies). A 5-point Likert-type
      scale was used for responses. Psychometric analysis included itemetric
      performance, confirmatory factor analysis, test-retest reliability, and
      evaluation of subject's responses to the general CF-care questions. RESULTS: One
      hundred twenty-nine individuals returned completed surveys (39%; 66 males and 63
      females; age range, 2 months to 47 years). FEV(1)values were 21 to 155% predicted
      (mean, 76%; n = 82). Disease severity was as follows: 60 mild, 47 moderate, and
      14 severe. Seventy-nine subjects used postural drainage, percussion, and
      vibration (PDPV), 21 used a flutter device, and 14 used high-frequency chest wall
      oscillation (HFCWO). Five subjects used more than one technique. Internal
      consistency analysis found an overall coefficient alpha of 0.87 (range, 0.74 to
      0.89 for four domains). Factor analysis demonstrated domains for efficacy,
      convenience, comfort, and overall satisfaction. Mean total satisfaction scores
      differed significantly among therapies (R(2) = 0. 118; F[ 2,111] = 7.56; p =
      0.0008): PDPV, 3.8 (SD = 0.6); Flutter, 4. 3 (SD = 0.5); and HFCWO, 4.1 (SD =
      0.5). Therapies also differed significantly on all subscores. Perceived
      importance of CPT and compliance with CPT increased linearly with disease
      severity. Overall satisfaction was positively correlated with CPT compliance.
      CONCLUSIONS: The CPT satisfaction survey has good reliability and content
      validity. Significant differences in patient satisfaction exist among therapies.
      Sicker patients recognize the importance of, and demonstrate better compliance
      with prescribed CPT. Increased satisfaction is associated with better compliance
      with therapy.

PMID- 10893366
TI  - Variability in performance of timed walk tests in pulmonary rehabilitation
      programs.
AB  - STUDY OBJECTIVE: To describe variability in the conduct of walk tests in
      pulmonary rehabilitation programs. DESIGN: : Analysis of information obtained by
      means of a structured written questionnaire. SETTING: Outpatient pulmonary
      rehabilitation programs in the United States and Canada. PARTICIPANTS: Clinical
      coordinators of 75 pulmonary rehabilitation programs. INTERVENTIONS: None
      RESULTS: Timed walk tests were obtained in 71 of 99 programs surveyed.
      Considerable variability in all aspects of testing practices was evident. Fifty
      seven respondents (80%) based results on a single walk. Walk tests were completed
      in a hallway (73%), on a walking track (9%), and on a treadmill (7%). In 29
      programs (44%), a walk supervisor carried or pulled the oxygen source, while in
      25 programs (38%), the oxygen was carried or pulled by the patient. Informal
      nonstandardized instructions were provided to patients prior to walking in 41
      programs (58%). In 53 programs (76%), the walk supervisor could direct a patient
      to speed up, to slow down, or to rest. Evaluations of breathlessness and
      perceived exertion were measured during the walk by 73% and 16% of programs,
      respectively. CONCLUSIONS: Practices regarding performance of timed walk tests
      are poorly standardized among pulmonary rehabilitation programs. Further research
      is needed to evaluate the impact of certain variations in testing practices on
      test results.

PMID- 10893367
TI  - Results of a home-based training program for patients with COPD.
AB  - OBJECTIVES: To have a group of COPD patients undergo a simple program of home
      based exercise training, using the shuttle walking test (SWT) to standardize the
      intensity of training. METHODS: Sixty patients participated, randomly distributed
      into two groups (rehabilitation and control) of 30 patients each. The following
      evaluations were carried out at baseline and at 12 weeks: (1) pulmonary function
      studies; (2) SWT; (3) submaximal intensity resistance test; (4) cycle ergometer
      test; (5) quality of life; and (6) dyspnea. The rehabilitation group underwent a
      lower-extremity training program. Walking was selected as the type of exercise.
      The intensity of training was set at 70% of the maximum speed attained on the
      SWT. Divided sessions were held, lasting 1 h, 6 days/wk, at home, with a checkup
      every 2 weeks. The duration of the program was 12 weeks. RESULTS: The following
      patients completed the study: 20 patients (66.6%) from the rehabilitation group
      (mean [+/- SD]) age, 64.3 +/- 8.3 years; mean FEV(1), 41.7 +/- 15.6% of
      predicted); and 17 patients (56.6%) from the control group (mean age, 63.1 +/-
      6.9 years; mean FEV(1), 40 +/- 16.4% of predicted). We found no changes in
      pulmonary function or effort parameters (SWT or cycle ergometer) in the
      rehabilitation group at 12 weeks. A twofold increase (1,274 +/- 980 to 2,651 +/-
      2,056 m; p < 0.001) was achieved in the submaximal intensity resistance test,
      with less dyspnea at the conclusion of the test (p = 0.05). Significant
      improvement also was achieved in basal dyspnea and, both statistically and
      clinically, in the quality of life. Significant changes were not achieved in the
      control group patients. CONCLUSIONS: A simple home-based program of exercise
      training achieved improvement in exercise tolerance, posteffort dyspnea, basal
      dyspnea, and quality of life in COPD patients.

PMID- 10893368
TI  - Prospective study of functional status and quality of life before and after lung
      transplantation.
AB  - STUDY OBJECTIVES: To determine the impact of lung transplantation on patients'
      function and quality of life (QOL), 10 lung transplant patients were followed
      from before transplantation to 3 months after transplantation. The following
      variables were examined: (1) perceived functional status; (2) respiratory
      function; (3) moods; (4) satisfaction with overall QOL and health; and (5)
      thoughts about the decision to undergo lung transplantation. DESIGN: A
      longitudinal, small-group, repeated-measures design. SETTING: A large Midwest
      university medical center. MEASUREMENTS AND RESULTS: Several instruments were
      used to measure perceived health, QOL, functional status, and respiratory
      function. The perceived improvement in physical function after transplantation
      was accompanied by increased satisfaction with physical strength, current health,
      and QOL. In addition, dramatic improvements in pulmonary function were seen after
      transplantation (FVC, FEV(1), and forced expiratory flow at 25 to 75% of FVC);
      however, only the FEV(1) values significantly improved between 1 and 3 months
      after transplantation. For example, the FEV(1) (mean +/- SD) increased from 22 +/
      11% of predicted before transplantation to 46 +/- 12% and 55 +/- 14% of
      predicted at 1 month and 3 months after transplantation, respectively. Although
      the total number of psychological symptoms did not decrease significantly over
      time, the intensity and distress associated with the symptoms did. Psychological
      function scores did not change significantly. Ninety percent of the subjects
      reported being very satisfied with their transplant decision. CONCLUSIONS: Lung
      transplantation significantly improved the subjects' overall function and their
      satisfaction with their QOL and health status. However, since this report only
      addressed data for the first 3 months after transplantation, additional
      longitudinal research is needed to further elucidate the experiences and outcomes
      associated with lung transplantation.

PMID- 10893370
TI  - Beliefs among pulmonologists and thoracic surgeons in the therapeutic approach to
      non-small cell lung cancer.
AB  - STUDY OBJECTIVES: The physicians who initially evaluate patients with non-small
      cell lung cancer (NSCLC) strongly impact the course of therapy. Their beliefs in
      treatment and prognosis may contribute to practices of variable quality and
      appropriateness. We sought to better describe beliefs among pulmonologists and
      thoracic surgeons who were selected for guiding early therapy and referrals in
      patients with NSCLC. DESIGN: Mail questionnaire focusing on survival estimates,
      treatment perceptions, and referral patterns. PARTICIPANTS: Twelve hundred
      pulmonologists and 800 thoracic surgeons who were clinically active members of
      the American College of Chest Physicians. MEASUREMENTS AND RESULTS: Response
      rates of 50% for pulmonologists and 52% for thoracic surgeons were obtained after
      two mailings. Five-year survival estimates for patients with resected stage I
      NSCLC revealed that 30% of respondents overestimated survival rates and 18%
      underestimated survival rates. The underestimation of survival rate was found
      among more respondents who are practicing pulmonology than thoracic surgery (22%
      vs 10% [corrected], respectively), who were trained before 1980 than after 1980
      (29% vs 10% [corrected], respectively), and who were seeing < 10 lung cancer
      patients annually than those who were seeing > 25 (31% vs 0.14%, respectively).
      Beliefs in the survival benefit of adjuvant chemotherapy or of radiation in stage
      I-IIIA disease divided respondents within both specialties. Chemotherapy plus
      radiation vs radiation alone in unresectable stage IIIA-B NSCLC was viewed as
      benefiting survival less often by physicians seeing < 10 lung cancer patients
      annually rather than > 25 (57% vs 77% [corrected], respectively) and by
      physicians underestimating rather than correctly estimating survival in early
      stage disease (58% vs 72% [corrected], respectively). Chemotherapy was believed
      to confer survival benefits in patients with stage IV disease by one third of
      respondents. CONCLUSIONS: Certain physician characteristics, particularly the
      length of time since training and NSCLC patient volume, are associated with
      beliefs not conclusively supported in the medical literature or with opinions
      inconsistent within and between specialties.

PMID- 10893369
TI  - Induction therapy for non-small cell lung cancer with involved mediastinal nodes
      in multiple stations.
AB  - BACKGROUND: Metastasis to multiple stations of mediastinal nodes is associated
      with a poor prognosis. OBJECTIVE: : We prospectively examined the efficacy of
      induction therapy plus surgery in patients with non-small cell lung cancer and
      metastases at multiple stations of mediastinal (N2) lymph nodes. METHODS: Among
      the 1,085 patients who underwent surgery for primary non-small cell lung
      carcinoma from 1985 to 1997, those with clinical N2 disease of involved multiple
      stations, defined as bulky, mediastinal, lymph node metastases on CT scans,
      received induction therapy, consisting of cisplatin-based chemotherapy and
      radiation of 40 Gy. RESULTS: Of the 88 eligible patients entered into the study,
      51 (58%) had multiple stations of N2 nodes affected preoperatively, as
      demonstrated by pathologic examination. Neither operative mortality nor fatal,
      treatment-related complications occurred during hospitalization. Patients who
      underwent complete resection had significantly longer survivals than did those
      who underwent incomplete resection (p = 0. 001). Among patients who underwent
      complete resection, the survival rate for patients with pathologically downstaged
      disease was significantly higher than that for patients whose disease was not
      downstaged (p = 0.009). Among patients with multiple stations of pN2 nodes
      involved who had undergone complete resection, those who received induction
      therapy for bulky N2 disease had a significantly better prognosis than did those
      undergoing surgery alone for nonbulky N2 disease (p = 0.03). CONCLUSIONS:
      Induction therapy prolonged the survival of patients with non-small cell lung
      cancer and mediastinal nodes involved at multiple stations. Survival was better
      when complete resection and downstaging of the disease were achieved after
      induction therapy.

PMID- 10893371
TI  - Clinical course, prognostic factors, and outcome prediction for HIV patients in
      the ICU. The PIP (Pulmonary complications, ICU support, and prognostic factors in
      hospitalized patients with HIV) study.
AB  - STUDY OBJECTIVE: To describe the clinical course and prognostic factors in
      patients with HIV admitted to the ICU. DESIGN: Prospective, observational.
      SETTING: A university-affiliated medical center. METHODS: : We included 169
      consecutive ICU admissions, from April 1995 through March 1999, of 141 adults
      with HIV. Data collected included APACHE (acute physiology and chronic health
      evaluation) II score, CD4(+) lymphocyte count, serum albumin level, in-hospital
      mortality, and the development of organ failure, systemic inflammatory response
      syndrome (SIRS), and ARDS. RESULTS: The ICU admission rate of hospitalized
      patients with HIV infection was 12%. The most common reason for ICU admission was
      respiratory failure, occurring in 65 patient admissions. Mechanical ventilation
      was required in 91 admissions (54%), ARDS developed in 37 admissions (22%),
      Pneumocystis carinii pneumonia was diagnosed in 24 admissions (14%), and SIRS
      developed in 126 admissions (75%). One or more organ failures developed in 131
      admissions (78%). The actual and predicted mortality rates were 29.6% and 45.2%,
      respectively, with a standardized mortality ratio of 0.65. The most frequent
      immediate cause of death was bacterial infection. The CD4(+) lymphocyte count
      (median, 27.5 cells/microL vs 59 cells/microL; p = 0.0310) and serum albumin
      level (median 2.2 g/dL vs 2.6 g/dL; p = 0.0355) of nonsurvivors were lower and
      the APACHE II score (median, 30 vs 21; p < 0.0001) was higher, compared to those
      of survivors. A higher APACHE II score (odds ratio [OR], 1.11; 95% confidence
      interval [CI], 1.05 to 1.16) and a transfer from another hospital ward (OR, 3.03;
      95% CI, 1.20 to 7.68) were independently associated with increased mortality. The
      median number of organ failures that developed in survivors was one, compared to
      four in nonsurvivors (p < 0.0001). CONCLUSIONS: The outcome of HIV-infected
      patients admitted to the ICU has improved over the years. The CD4 count does not
      correlate with in-hospital mortality. Higher APACHE II scores and a transfer from
      another hospital ward are associated with a poor outcome.

PMID- 10893372
TI  - The influence of inadequate antimicrobial treatment of bloodstream infections on
      patient outcomes in the ICU setting.
AB  - STUDY OBJECTIVE: To evaluate the relationship between the adequacy of
      antimicrobial treatment for bloodstream infections and clinical outcomes among
      patients requiring ICU admission. DESIGN: Prospective cohort study. SETTING: A
      medical ICU (19 beds) and a surgical ICU (18 beds) from a university-affiliated
      urban teaching hospital. PATIENTS: Between July 1997 and July 1999, 492 patients
      were prospectively evaluated. INTERVENTION: Prospective patient surveillance and
      data collection. RESULTS: One hundred forty-seven patients (29.9%) received
      inadequate antimicrobial treatment for their bloodstream infections. The hospital
      mortality rate of patients with a bloodstream infection receiving inadequate
      antimicrobial treatment (61.9%) was statistically greater than the hospital
      mortality rate of patients with a bloodstream infection who received adequate
      antimicrobial treatment (28.4%; relative risk, 2. 18; 95% confidence interval
      [CI], 1.77 to 2.69; p < 0.001). Multiple logistic regression analysis identified
      the administration of inadequate antimicrobial treatment as an independent
      determinant of hospital mortality (adjusted odds ratio [AOR], 6.86; 95% CI, 5.09
      to 9.24; p < 0.001). The most commonly identified bloodstream pathogens and their
      associated rates of inadequate antimicrobial treatment included vancomycin
      resistant enterococci (n = 17; 100%), Candida species (n = 41; 95.1%), oxacillin
      resistant Staphylococcus aureus (n = 46; 32.6%), coagulase-negative staphylococci
      (n = 96; 21.9%), and Pseudomonas aeruginosa (n = 22; 10.0%). A statistically
      significant relationship was found between the rates of inadequate antimicrobial
      treatment for individual microorganisms and their associated rates of hospital
      mortality (Spearman correlation coefficient = 0.8287; p = 0.006). Multiple
      logistic regression analysis also demonstrated that a bloodstream infection
      attributed to Candida species (AOR, 51.86; 95% CI, 24.57 to 109.49; p < 0.001),
      prior administration of antibiotics during the same hospitalization (AOR, 2.08;
      95% CI, 1.58 to 2.74; p = 0.008), decreasing serum albumin concentrations (1-g/dL
      decrements) (AOR, 1.37; 95% CI, 1.21 to 1.56; p = 0.014), and increasing central
      catheter duration (1-day increments) (AOR, 1.03; 95% CI, 1.02 to 1.04; p = 0.008)
      were independently associated with the administration of inadequate antimicrobial
      treatment. CONCLUSIONS: The administration of inadequate antimicrobial treatment
      to critically ill patients with bloodstream infections is associated with a
      greater hospital mortality compared with adequate antimicrobial treatment of
      bloodstream infections. These data suggest that clinical efforts should be aimed
      at reducing the administration of inadequate antimicrobial treatment to
      hospitalized patients with bloodstream infections, especially individuals
      infected with antibiotic-resistant bacteria and Candida species.

PMID- 10893373
TI  - The effects of early and repeated prone positioning in pediatric patients with
      acute lung injury.
AB  - STUDY OBJECTIVE: To describe the physiologic changes and to evaluate the safety
      of placing pediatric patients with acute lung injury (ALI) prone for 20 h/d
      during the acute phase of their illness. DESIGN: Single-center prospective case
      series. SETTING: Tertiary-level pediatric ICU. PATIENTS: Consecutive patients
      with bilateral pulmonary parenchymal disease requiring intubation and mechanical
      ventilation with a PaO(2)/fraction of inspired oxygen (FIO(2)) ratio </= 300 mm
      Hg. INTERVENTIONS: Patients were enrolled as soon as possible after meeting
      criteria and were placed in a prone position for 20 h/d daily until clinical
      improvement or death occurred. MEASUREMENTS AND RESULTS: Twenty-five pediatric
      patients who had ALI/ARDS, ranging in age from 2 months to 17 years, were placed
      in a prone position within 19 h of meeting the study criteria for a median time
      of 4 days, which accounted for 47% of their time receiving mechanical
      ventilation. Eighty-four percent of patients (n = 21) were categorized as overall
      responders to prone positioning because they experienced more days of increases
      of >/= 20 mm Hg in PaO(2)/FIO(2) ratio or a decrease of >/= 10% in oxygenation
      index when shifted from a supine to a prone position during the study period.
      During the 107 patient-days and 214 positioning cycles, no critical incidents
      occurred. Furthermore, no patient experienced a persistent decrease in oxygen
      saturation as measured by pulse oximetry (SpO(2)) of > 10% from values obtained
      when in the supine position, failed to keep their SpO(2) at > 85%, or experienced
      an increased respiratory rate of > 40 breaths/min when prone. Using the COMFORT
      score, patients were objectively rated to be equally comfortable in both the
      supine and prone positions. Patients also were able to resume spontaneous
      ventilation and to progress toward endotracheal extubation while in the prone
      position. Iatrogenic injury associated with prolonged prone positioning included
      stage II pressure ulcers in six patients (24%). CONCLUSIONS: The pediatric
      patients in this series demonstrated improvements in oxygenation without serious
      iatrogenic injury after prone positioning. This study provides a foundation for a
      prospective randomized study investigating the effect of early and repeated prone
      positioning on clinical outcomes in pediatric patients with ALI.

PMID- 10893374
TI  - Function and composition of pulmonary surfactant and surfactant-derived fatty
      acid profiles are altered in young adults with cystic fibrosis.
AB  - STUDY OBJECTIVES: To determine whether chronic lung inflammation in young adult
      patients with cystic fibrosis (CF) alters the composition and function of
      surfactant and surfactant components in bronchoalveolar secretions. DESIGN: A
      prospective, descriptive study. SETTING: An adult CF center in a tertiary health
      care center. PARTICIPANTS: Thirteen normal volunteer (NV) subjects recruited via
      local advertising and 15 CF patients recruited from the CF center. INTERVENTIONS:
      None. MEASUREMENTS AND RESULTS: We performed BAL and measured surfactant
      associated protein A (SP-A) via enzyme-linked immunosorbent assay in BAL fluid
      (BALF), and quantitated total phospholipid, phospholipid subclass, and fatty acid
      subclass content of extracted BALF. We also determined the protein and
      phospholipid content, SP-A content, and functional characteristics of surfactant
      isolated from BALF via high-speed centrifugation. The phospholipid-to-protein
      ratio (milligram/milligram) of surfactant isolated by centrifugation (mean +/-
      SEM) was 1.01 +/- 0.07 for NV subjects and 2.62 +/- 0.42 for CF patients (p =
      0.0001). Minimal surface tension was < 1 dyne.s.cm(-5) in all samples from NV
      subjects, but 21.9 +/- 0.73 dyne.s.cm(-5) for surfactant from CF patients.
      Immunoblotting of isolated surfactant revealed a marked decrease in SP-A for CF
      patients, compared to NV subjects. However, mean concentrations of SP-A in BALF
      that had not been subjected to high-speed centrifugation to isolate surfactant
      were not significantly different for CF patients (4.7 +/- 0.8 microgram/mL) vs NV
      subjects (4.6 +/- 0.2 microgram/mL). Additionally, phospholipid-to-protein ratios
      (0.32 +/- 0.04 for NV subjects vs 0.10 +/- 0.02 for CF patients; p < 0.0001) in
      extracted uncentrifuged BALF, and SP-A-to-protein ratios (microgram/milligram) in
      BALF were significantly depressed (74 +/- 8 for NV subjects vs 16 +/- 3 for CF
      patients; p < 0.0001). The phospholipid and fatty acid subclass profiles of
      extracted CF BALF vs NV BALF revealed a decreased mean phosphatidylcholine-to
      sphingomyelin ratio (20.7 +/- 10.0 vs 55.2 +/- 8.7; p = 0.002), increased oleic
      acid content (12.1 +/- 2.3 nmol/mL vs 3.2 +/- 0.9 nmol/mL; p < 0.01), and
      increased arachidonic acid content (2.2 +/- 0.5 nmol/mL vs 0.6 +/- 0.3 nmol/mL; p
      < 0.05) for CF patients. CONCLUSIONS: Altered phospholipid-to-protein ratios and
      phospholipid subclasses, altered surfactant-derived fatty acid profiles, high
      minimal surface tension, and decreased association of SP-A with lipid components
      of isolated surfactant indicate that surfactant components are considerably
      altered and dysfunctional in lower respiratory tract secretions of CF patients.
      Surfactant composition and function are altered in CF, and the pattern of
      phospholipid and surfactant-derived fatty acid subclass alterations in CF are
      characteristic of ongoing lung injury and may depress surfactant function.

PMID- 10893375
TI  - Nonselective endothelin-receptor antagonism attenuates hemodynamic changes after
      massive pulmonary air embolism in dogs.
AB  - STUDY OBJECTIVES: To evaluate the effects of nonselective endothelin (ET)
      receptor antagonism on the hemodynamic changes and serum thromboxane (TX)-A(2)
      levels after a massive pulmonary air embolism (PAE) in dogs. DESIGN: Prospective
      trial. SETTING: University laboratory. INTERVENTIONS: Anesthetized mongrel dogs
      (ET-receptor antagonist group; n = 6) received a bolus injection of 1 mg of the
      nonselective ET-A/ET-B-receptor antagonist PD 145065 (Sigma Chemical; St. Louis,
      MO), and dogs in the control group (n = 6) received saline solution. Hemodynamic
      data were recorded 5 min after the administration of antagonist or saline
      solution. Subsequently, each dog received 2.5-mL air/kg via the right femoral
      vein (the PAE), and the hemodynamic data were recorded for up to 60 min
      thereafter. Arterial blood samples were drawn at baseline and 15 min after PAE
      for the determination of plasma TX-A(2), measured by enzyme-linked immunosorbent
      assay as TX-B(2) (the stable metabolite of TX-A(2)). RESULTS: PD 145065 alone
      produced no hemodynamic effects. However, dogs pretreated with PD 145065 had
      significantly lower increases in mean pulmonary arterial pressure and in
      pulmonary vascular resistance after the PAE (116% and 165%, respectively)
      compared to the control dogs (187% and 367%, respectively). The mean arterial
      pressure (MAP), cardiac index (CI), and plasma TX-B(2) levels were unaltered
      after PAE in the presence of ET-receptor antagonist, whereas CI and MAP decreased
      5 to 10 min after PAE, and TX-B(2) concentrations increased 15 min after PAE in
      control dogs (p < 0.05 in all cases). CONCLUSIONS: Nonselective antagonism of ET
      receptors attenuates the pulmonary hypertension and blunts the TX-A(2) release
      caused by massive PAE in dogs.

PMID- 10893376
TI  - Clara cell secretory protein. Levels in BAL fluid after smoking cessation.
AB  - STUDY OBJECTIVES: The bronchiolar Clara cell is a major target for tobacco smoke
      exposure. To improve our understanding of the putative regenerative/repair
      mechanism(s) in the bronchiolar epithelium, we measured the levels of the Clara
      cell secretory protein (CCSP) in BAL fluid in healthy volunteers following
      smoking cessation. DESIGN: BAL was performed before smoking cessation, and at 1,
      3, 6, 9, and 15 months following smoking cessation, in eight healthy volunteers
      with a previous mean cigarette consumption of 19 pack-years. The levels of CCSP
      in BAL fluid were assessed in immunoblotting experiments using an antibody
      against human CCSP. RESULTS: Significantly (p < 0.05) higher levels of CCSP in
      BAL fluid were observed at 3, 6, and 9 months after smoking cessation, while the
      levels of CCSP in BAL fluid at 15 months after smoking cessation were the same as
      those before smoking cessation. CONCLUSIONS: Despite the long history of smoking
      among patients in the present study group, signs of early regeneration in the
      bronchiolar epithelium were noted, in that the levels of CCSP in BAL fluid were
      elevated at the indicated time points following smoking cessation. Furthermore,
      we propose that the insult to the bronchiolar epithelium made by cigarette
      smoking caused the levels of CCSP in the BAL fluid at 15 months after smoking
      cessation to return to the levels noted before smoking cessation. The present
      study suggests a role for CCSP as a marker for nonciliated bronchiolar cell
      function.

PMID- 10893377
TI  - Novel flexible bronchoscope and single-use disposable-sheath endoscope system. A
      preliminary technology evaluation.
AB  - OBJECTIVE: To measure image clarity, ease of use, and handling performance of a
      flexible fiberoptic bronchoscope (B-F 100; Vision Sciences; Natick, MA) and
      sterile single-use disposable-sheath endoscope system (BS-F21 EndoSheath; Vision
      Sciences). DESIGN: Prospective, multicenter diagnostic technology evaluation of a
      medical device newly approved by the US Food and Drug Administration. SETTING:
      Three tertiary care referral centers with busy bronchoscopy practices. PATIENTS:
      Twenty-four patients undergoing bronchoscopy with a flexible fiberoptic
      bronchoscope and disposable sheath endoscope system. METHODS: Flexible
      bronchoscopy was performed through a transnasal or transoral route after topical
      upper airway anesthesia using standard techniques. After each procedure, the
      bronchoscopist rated the performance of the medical device under study using a
      linear scale of 1 (poor) to 5 (excellent and equal to that of a conventional
      flexible fiberoptic bronchoscope). RESULTS: Mean performance ratings were > 4.0
      (range, 4.17 to 4.63) for image clarity, illumination, lack of fogging, distal
      tip angulation, and ease of transnasal passage. All other ratings were > 3.0
      (range, 3.54 to 3.87), the lowest of which was handling comfort. CONCLUSION: The
      flexible fiberoptic bronchoscope with sterile single-use disposable-sheath
      endoscope system has the potential to reduce scope downtime by eliminating the
      need for high-level disinfection between procedures. Illumination, image clarity,
      and ease of insertion are very good, justifying future prospective studies
      comparing this device to conventional flexible fiberoptic bronchoscopes.

PMID- 10893378
TI  - The role of anticholinergics in bronchoscopy. A randomized clinical trial.
AB  - BACKGROUND: Anticholinergic medications have been utilized frequently prior to
      bronchoscopy and are thought to facilitate the drying of secretions to limit the
      amount of required topical anesthetic on the airway mucosa, prevent cardiac
      arrhythmias during the procedure, and increase patient comfort. OBJECTIVE: To
      determine if atropine or glycopyrrolate, two anticholinergic agents utilized most
      frequently in this setting, have any significant role for this purpose. DESIGN:
      Double-blind, placebo-controlled study, in which patients were randomly selected
      to receive atropine (0.01 mg/kg body weight, IM injection), glycopyrrolate (0.005
      mg/kg, IM injection), or saline solution placebo (approximately 2 mL, IM
      injection) 15 to 45 min prior to being sedated with midazolam until judged to be
      lightly sedated. SETTING: A large academic teaching hospital in the midwestern
      United States. PARTICIPANTS: Two hundred seventeen outpatients referred for
      bronchoscopy who satisfied inclusion and exclusion criteria. MEASUREMENTS AND
      RESULTS: Using a modified visual analog scale (0 to 100 mm), the bronchoscopist
      and the nurse anesthetist estimated the antisialagogic effect, effectiveness in
      cough suppression, and overall patient comfort during the procedure. The patients
      completed a similar questionnaire after recovering from the procedure. Patients
      were also monitored for complications (cardiac arrhythmias, oxygen desaturation,
      hypertension, wheezing, or coughing severe enough to curtail the procedure).
      There was no significant difference found among atropine, glycopyrrolate, and
      placebo for the primary end point of secretion control. In addition, there was no
      difference found between either medication and placebo for effectiveness of cough
      suppression, amount of topical anesthetic used, complication rates, or overall
      patient comfort. CONCLUSION: The use of anticholinergic agents prior to
      bronchoscopy did not affect performance of bronchoscopy or complication rates,
      and there was no appreciable benefit from the resultant reduction in airway
      secretions in a population of patients receiving concurrent sedation with
      benzodiazepines.

PMID- 10893379
TI  - Do bacteria cause exacerbations of COPD?
AB  - Exacerbations of COPD, which include combinations of dyspnea, cough, wheezing,
      increased sputum production (and a change in its color to green or yellow), are
      common. The role of bacterial infection in causing these episodes and the value
      of antibiotic therapy for them are debated. An assessment of the microbiological
      studies indicates that conventional bacterial respiratory pathogens, such as
      Streptococcus pneumoniae and Haemophilus influenzae, are absent in about 50% of
      attacks. The frequency of isolating these organisms, which often colonize the
      bronchi of patients in stable condition, does not seem to increase during
      exacerbations, and their density typically remains unchanged. Serologic studies
      generally fail to show rises in antibody titers to H influenzae; the only report
      available demonstrates none to Haemophilus parainfluenzae; and the sole
      investigation of S pneumoniae is inconclusive. Trials with vaccines against S
      pneumoniae and H influenzae show no clear benefit in reducing exacerbations. The
      histologic findings of bronchial biopsies and cytologic studies of sputum show
      predominantly increased eosinophils, rather than neutrophils, contrary to what is
      expected with bacterial infections. The randomized, placebo-controlled trials
      generally show no benefit for antibiotics, but most have studied few patients. A
      meta-analysis of these demonstrated no clinically significant advantage to
      antimicrobial therapy. The largest trials suggest that antibiotics confer no
      advantage for mild episodes; with more severe attacks, in which patients should
      receive systemic corticosteroids, the addition of antimicrobial therapy is
      probably not helpful.

PMID- 10893380
TI  - The role of bacteria in exacerbations of COPD. A constructive view.
AB  - The role of infection in exacerbations of COPD remains controversial and
      incompletely understood. Although some investigators believe that bacteria are
      not important for patients with exacerbation, we disagree and believe that
      patients with at least two of the three cardinal symptoms of exacerbation should
      receive antibiotic therapy. With an open-minded view of the area, we review the
      data, showing that bacteriologic studies, pathologic investigations, and clinical
      trials all support roles for bacteria and antibiotic therapy in this disease.
      Still, many questions remain, and future studies will be needed to better define
      the mechanisms of bacterial invasion in the bronchitic patient and to develop
      effective vaccines to prevent exacerbations. In the meantime, we must rely on
      antibiotic therapy, and we will need prospective studies to corroborate
      preliminary findings showing that different patients may require different
      therapies; thus, patient subsetting may be vital in the selection of antibiotic
      therapy for exacerbations of COPD.

PMID- 10893381
TI  - Brahms' lullaby revisited. Did the composer have obstructive sleep apnea?

PMID- 10893382
TI  - The diagnosis and management of hypertensive crises.
AB  - Severe hypertension is a common clinical problem in the United States,
      encountered in various clinical settings. Although various terms have been
      applied to severe hypertension, such as hypertensive crises, emergencies, or
      urgencies, they are all characterized by acute elevations in BP that may be
      associated with end-organ damage (hypertensive crisis). The immediate reduction
      of BP is only required in patients with acute end-organ damage. Hypertension
      associated with cerebral infarction or intracerebral hemorrhage only rarely
      requires treatment. While nitroprusside is commonly used to treat severe
      hypertension, it is an extremely toxic drug that should only be used in rare
      circumstances. Furthermore, the short-acting calcium channel blocker nifedipine
      is associated with significant morbidity and should be avoided. Today, a wide
      range of pharmacologic alternatives are available to the practitioner to control
      severe hypertension. This article reviews some of the current concepts and common
      misconceptions in the management of patients with acutely elevated BP.

PMID- 10893383
TI  - Top ten list in lung cancer.

PMID- 10893384
TI  - Progressive infiltrates and eosinophilia with multiple possible causes.

PMID- 10893385
TI  - The results of thoracoscopic surgery for primary spontaneous pneumothorax.
AB  - OBJECTIVE: To review our experience of video-assisted thoracoscopic surgery for
      the treatment of primary spontaneous pneumothorax. DESIGN: Longitudinal cohort
      study following up consecutive patients for 3 to 4.3 years. SETTING: Thoracic
      Surgery Department, Chest Diseases Hospital, Kuwait. PATIENTS AND INTERVENTION:
      Seventy-two consecutive patients undergoing thoracoscopy for primary spontaneous
      pneumothorax from January 1994 to June 1996. RESULTS: The mean age of the
      patients was 25 years (range, 15 to 40 years), and 67 were men (93%). All
      patients were successfully treated using video-assisted thoracoscopic technique.
      Recurrent pneumothorax was the most frequent indication for surgery, occurring in
      49 patients. The most common method of management was stapling of an identified
      bleb, which was done in 56 cases. Pleurodesis was achieved by gauze abrasion (n =
      39) and apical pleurectomy (n = 33). Postoperative prolonged air leak occurred in
      five patients (6.9%). There were no deaths attributable to the procedure. The
      mean (+/-SD) postoperative hospital stay was 4 +/- 2 days. Mean follow-up is 42
      months (range, 36 to 54 months) for all patients. Pneumothorax recurred in four
      patients (5.5%) in whom pleural abrasion was done. The recurrences occurred in
      the first year of follow-up, three required a reoperation, and one healed by rest
      without pleural drainage. CONCLUSIONS: Video-assisted thoracoscopic surgery is a
      safe procedure in the treatment of primary spontaneous pneumothorax. Apical
      pleurectomy is a more effective way of producing pleural symphysis. Long-term
      follow-up did not increase the rate of recurrence.

PMID- 10893386
TI  - A 48-year-old smoker with cough and weight loss.

PMID- 10893387
TI  - Persistent severe hypocapnia and alkalemia in a 40-year-old woman.

PMID- 10893388
TI  - Occupational asthma caused by pyrazolone derivative used in silver halide
      photographic paper.
AB  - Occupational asthma has been documented in workers exposed to a wide variety of
      chemical compounds. Reactive dyes have been described as causing occupational
      asthma in textile industry workers. We report a case of occupational asthma
      resulting from exposure to pyrazolone dye used in silver halide photographic
      paper. There is a need for both further surveys of workers exposed to other
      reactive dyes and careful preventive measures in the handling of such compounds.

PMID- 10893389
TI  - Recurrent ventricular fibrillation in a marathon runner during exercise testing.
AB  - We report a case of a marathon runner who presented with chest tightness, ST
      segment depression, and ventricular fibrillation following treadmill exercise
      testing. At cardiac catheterization, the patient was found to have an isolated
      lesion in the left anterior descending (LAD) artery that was hemodynamically
      insignificant by accepted angiographic and coronary flow reserve standards.
      Ventricular fibrillation was thought to be idiopathic, and an implantable
      cardioverter defibrillator was placed. Chest pain and ST-segment depression
      followed by ventricular fibrillation was reproduced during follow-up treadmill
      testing, prompting reconsideration of the original diagnostic hypothesis. A
      coronary stent was deployed in the LAD artery. The patient has been asymptomatic
      and arrhythmia free during follow-up treadmill testing and recreational running.

PMID- 10893390
TI  - Recurrent, self-limited, menstrual-associated bronchiolitis obliterans organizing
      pneumonia.
AB  - A 39-year-old woman presented with recurrent acute illness, characterized by high
      grade fever, pleuritic chest pain, and unilateral nodular infiltrate on chest
      radiograph. During the follow-up period, there were six similar episodes, each
      starting 2 to 3 days prior to her menstrual period and resolving within 5 to 10
      days. Persistent symptoms in the seventh episode led us to perform an open lung
      biopsy; the specimen showed histologic changes compatible with the diagnosis of
      bronchiolitis obliterans organizing pneumonia (BOOP). To the best of our
      knowledge, this is the first report describing BOOP in association with a
      menstrual period. This exceptional case emphasizes the wide and unexpected
      spectrum of this disease.

PMID- 10893391
TI  - An uncommon etiology of isolated pleural effusion. The ovarian hyperstimulation
      syndrome.
AB  - We report three cases of pleural effusion in the context of ovarian stimulation
      for in vitro fertilization. The ovarian hyperstimulation syndrome usually causes
      pleural effusion and ascites. When the latter is lacking, an isolated pleural
      effusion in a pregnant patient can be mistaken for pulmonary embolism. Early
      recognition of the condition should allow for an appropriate diagnostic and
      therapeutic management. Except for some rare but life-threatening complications,
      such as major hypovolemia or respiratory distress syndrome, the spontaneous
      outcome is usually favorable. The pathogenesis of this condition may involve an
      increase of capillary permeability due to the release of vasoactive mediators.

PMID- 10893392
TI  - Talc granulomatosis. A differential diagnosis of interstitial lung disease in HIV
      patients.
AB  - Consumers of adulterated drugs may present with talc-induced interstitial lung
      disease. A transbronchial biopsy specimen showing granulomas with intracellular
      talc crystals is necessary to confirm this diagnosis. In patients infected with
      HIV, such a condition can be indistinguishable at first glance from opportunistic
      infections or other pulmonary diseases. A case is presented of a seropositive
      patient whose chest radiographs showed a diffuse interstitial pattern.

PMID- 10893393
TI  - ECG changes in a 25-year-old woman with hypocalcemia due to hypoparathyroidism.
      Hypocalcemia mimicking acute myocardial infarction.
AB  - The case of a 25-year-old woman presenting with chest pain, ECG changes, and
      laboratory findings suggestive of myocardial infarction is reported. Cardiac
      catheterization showed impaired left ventricular performance but otherwise normal
      coronary arteries. Laboratory analyses revealed primary hypoparathyroidism, and
      supplementation with calcium and vitamin D(3) was initiated. There was subsequent
      improvement in laboratory findings as well as echocardiographically determined
      left ventricular performance. Thereafter, the patient remained asymptomatic.
      Apart from some persisting ECG repolarization disturbances, there was complete
      normalization of the initial changes. This case demonstrates a combination of
      clinical, blood biochemical, and ECG findings mimicking acute myocardial
      infarction.

PMID- 10893394
TI  - Laser resection of a pedunculated tracheal adenoma.
AB  - We report a case of tracheal adenoma presenting as hemoptysis and reversible
      airflow obstruction in an ex-smoker. A questionable defect in the tracheal air
      shadow on a posteroanterior chest radiograph was shown on CT to be a
      pedunculated, mid-tracheal tumor. Two-stage bronchoscopic laser resection
      resulted in an apparently normal tracheal mucosa. Results of postresection
      spirometry were normal.

PMID- 10893395
TI  - Alveolar hypoventilation syndrome in brainstem glioma with improvement after
      surgical resection.
AB  - A 3-year-old boy presented with brainstem astrocytoma and central alveolar
      hypoventilation syndrome. Contrast MRI of the brain showed that the tumor
      involved the cerebellum, with compression of brainstem, and resolved after
      surgical resection. Polysomnography performed before and after total tumor
      resection showed significant improvement in nocturnal respiratory rate,
      respiratory disturbance index, and oxygen desaturation. It is apparent that
      central alveolar hypoventilation syndrome secondary to brainstem tumor may
      improve after surgical resection for those with favorable anatomic location and
      histology. Serial polysomnography and MRI scans are useful for diagnosis and in
      the management plan, and to monitor progress.

PMID- 10893396
TI  - Unilateral diaphragmatic paralysis following bronchial artery embolization for
      hemoptysis.
AB  - Bronchial artery embolization is an effective treatment for patients with
      hemoptysis. Serious complications are rare, but may occur if the arterial supply
      to other structures is compromised. We present a case of unilateral diaphragmatic
      paralysis following bronchial artery embolization in a patient with cystic
      fibrosis. We believe that the diaphragmatic paralysis was due to the inadvertent
      obstruction of the left pericardiacophrenic artery during the embolization
      procedure, with compromise of the phrenic nerve blood supply. This resulted in a
      significant loss of lung function in our patient, who did not recover despite the
      subsequent return of diaphragmatic function.

PMID- 10893397
TI  - Survival following treatment of a cardiac malignant fibrous histiocytoma.
AB  - The authors report the successful surgical and chemotherapeutic management of a
      malignant fibrous histiocytoma with localization in the heart. This rare
      malignancy has specific morphologic characteristics and is diagnosed in adults
      when it is already locally aggressive or metastasized. The average survival time
      for patients with malignant fibrous histiocytoma is < 12 months. Neither clinical
      nor instrumental signs of recurrence have been detected in this patient after an
      aggressive surgical resection and a specific therapeutic approach.

PMID- 10893398
TI  - Cost-effective strategies following extubation of trauma patients.

PMID- 10893399
TI  - Measuring quality of life in interstitial lung disease.

PMID- 10893400
TI  - Safety of sputum induction.

PMID- 10893401
TI  - Eosinophilic bronchitis as a cause of cough.

PMID- 10893402
TI  - Propofol and too much sulfite?

PMID- 10893403
TI  - Nocturnal wheeze in asthmatic patients.

PMID- 10893404
TI  - Chronic cough revisited.

PMID- 10893405
TI  - Cough syncope treated with imidapril in an elderly patient with dysphagia.

PMID- 10893406
TI  - A mechanism of membrane neutral lipid acquisition by the microsomal triglyceride
      transfer protein.
AB  - The microsomal triglyceride transfer protein (MTP) and apolipoprotein B (apoB)
      belong to the vitellogenin (VTG) family of lipid transfer proteins. MTP is
      essential for the intracellular assembly and secretion of apoB-containing
      lipoproteins, the key intravascular lipid transport proteins in vertebrates. We
      report the predicted three-dimensional structure of the C-terminal lipid binding
      cavity of MTP, modeled on the crystal structure of the lamprey VTG gene product,
      lipovitellin. The cavity in MTP resembles those found in the intracellular lipid
      binding proteins and bactericidal/permeability-increasing protein. Two conserved
      helices, designated A and B, at the entrance to the MTP cavity mediate lipid
      acquisition and binding. Helix A (amino acids 725-736) interacts with membranes
      in a manner similar to viral fusion peptides. Mutation of helix A blocks the
      interaction of MTP with phospholipid vesicles containing triglyceride and impairs
      triglyceride binding. Mutations of helix B (amino acids 781-786) and of N780Y,
      which causes abetalipoproteinemia, have no impact on the interaction of MTP with
      phospholipid vesicles but impair triglyceride binding. We propose that insertion
      of helix A into lipid membranes is necessary for the acquisition of neutral
      lipids and that helix B is required for their transfer to the lipid binding
      cavity of MTP.

PMID- 10893407
TI  - Thrombin induces NO release from cultured rat microglia via protein kinase C,
      mitogen-activated protein kinase, and NF-kappa B.
AB  - Microglia, brain resident macrophages, become activated in brains injured due to
      trauma, ischemia, or neurodegenerative diseases. In this study, we found that
      thrombin treatment of microglia induced NO release/inducible nitric-oxide
      synthase expression, a prominent marker of activation. The effect of thrombin on
      NO release increased dose-dependently within the range of 5-20 units/ml. In
      immunoblot analyses, inducible nitric-oxide synthase expression was detected
      within 9 h after thrombin treatment. This effect of thrombin was significantly
      reduced by protein kinase C inhibitors, such as Go6976, bisindolylmaleimide, and
      Ro31-8220. Within 15 min, thrombin activated three subtypes of mitogen-activated
      protein kinases: extracellular signal-regulated kinase, p38, and c-Jun N-terminal
      kinase/stress-activated protein kinase. Inhibition of the extracellular signal
      regulated kinase pathway and p38 reduced the NO release of thrombin-treated
      microglia. Thrombin also activated nuclear factor kappaB (NF-kappaB) within 5
      min, and N-acetyl cysteine, an inhibitor of NF-kappaB, reduced NO release.
      However, thrombin receptor agonist peptide (an agonist of protease activated
      receptor-1 (PAR-1)), could not mimic the effect of thrombin, and cathepsin G, a
      PAR-1 inhibitor, did not reduce the effect of thrombin. These results suggest
      that thrombin can activate microglia via protein kinase C, mitogen-activated
      protein kinases, and NF-kappaB but that this occurs independently of PAR-1.

PMID- 10893408
TI  - Role of Grb7 targeting to focal contacts and its phosphorylation by focal
      adhesion kinase in regulation of cell migration.
AB  - We have previously described Grb7 association with focal adhesion kinase (FAK)
      and its possible roles in cell migration. In this paper, we investigated the
      mechanisms by which Grb7 and its association with FAK regulate cell migration. We
      found that deletion of the Grb7 SH2 domain eliminated partial Grb7 localization
      to focal contacts and its ability to stimulate cell migration. Replacement of the
      SH2 domain with the focal adhesion targeting sequence from FAK resulted in the
      focal contacts localization of the chimeric molecule and restored its activity to
      stimulate cell migration. We also found that Grb7 could be phosphorylated by FAK,
      which was dependent on the FAK kinase activity but not the presence of the Src
      family kinases. Cell adhesion also enhanced Grb7 phosphorylation in FAK+/+ cells
      but not FAK-/- cells, suggesting that Grb7 is a physiological substrate of FAK.
      Furthermore, both Grb7 and the chimeric molecule did not increase migration of
      FAK-/- cells, although the chimeric molecule was targeted to the focal contacts.
      Last, we showed that other Grb7 family members could not stimulate cell migration
      under similar experimental conditions. Together, these results demonstrate a role
      for Grb7 targeting to focal contacts and its phosphorylation by FAK in the
      regulation of cell migration.

PMID- 10893409
TI  - BiP and PDI cooperate in the oxidative folding of antibodies in vitro.
AB  - Immunoglobulin heavy chain binding protein (BiP), a member of the Hsp70 chaperone
      family, and the oxidoreductase protein-disulfide isomerase (PDI) play an
      important role in the folding and oxidation of proteins in the endoplasmic
      reticulum. However, it was not clear whether both cooperate in this process. We
      show here that BiP and PDI act synergistically in the in vitro folding of the
      denatured and reduced Fab fragment. Several ATP-dependent cycles of binding,
      release, and rebinding of the unfolded antibody chains by BiP are required for
      efficient reactivation. Our data suggest that in the absence of BiP unfolded
      antibody chains collapse rapidly upon refolding, rendering cysteine side chains
      inaccessible for PDI. BiP binds the unfolded polypeptide chains and keeps them in
      a conformation in which the cysteine residues are accessible for PDI. These
      findings support the idea of a network of folding helper proteins in the
      endoplasmic reticulum, which makes this organelle a dedicated protein-processing
      compartment.

PMID- 10893410
TI  - A broad spectrum Kunitz type serine protease inhibitor secreted by the hookworm
      Ancylostoma ceylanicum.
AB  - Although blood-feeding hookworms infect over a billion people worldwide, little
      is known about the molecular mechanisms through which these parasitic nematodes
      cause gastrointestinal hemorrhage and iron deficiency anemia. A cDNA
      corresponding to a secreted Kunitz type serine protease inhibitor has been cloned
      from adult Ancylostoma ceylanicum hookworm RNA. The translated sequence of the A.
      ceylanicum Kunitz type inhibitor 1 (AceKI-1) cDNA predicts a 16-amino acid
      secretory signal sequence, followed by a 68-amino acid mature protein with a
      molecular mass of 7889 daltons. Recombinant protein (rAceKI-1) was purified from
      induced lysates of Escherichia coli transformed with the rAceKI-1/pET 28a
      plasmid, and in vitro studies demonstrate that rAceKI-1 is a tight binding
      inhibitor of the serine proteases chymotrypsin, pancreatic elastase, neutrophil
      elastase, and trypsin. AceKI-1 inhibitory activity is present in soluble protein
      extracts and excretory/secretory products of adult hookworms but not the
      infective third stage larvae. The native AceKI-1 inhibitor has been purified to
      homogeneity from soluble extracts of adult A. ceylanicum using size exclusion and
      reverse-phase high pressure liquid chromatography. As a potent inhibitor of
      mammalian intestinal proteases, AceKI-1 may play a role in parasite survival and
      the pathogenesis of hookworm anemia.

PMID- 10893412
TI  - Cholesteryl ester transfer protein and phospholipid transfer protein have
      nonoverlapping functions in vivo.
AB  - Plasma phospholipid transfer protein (PLTP) and cholesteryl ester transfer
      protein (CETP) are homologous molecules that mediate neutral lipid and
      phospholipid exchange between plasma lipoproteins. Biochemical experiments
      suggest that only CETP can transfer neutral lipids but that there could be
      overlap in the ability of PLTP and CETP to transfer or exchange phospholipids.
      Recently developed PLTP gene knock-out (PLTP0) mice have complete deficiency of
      plasma phospholipid transfer activity and markedly reduced high density
      lipoprotein (HDL) levels. To see whether CETP can compensate for PLTP deficiency
      in vivo, we bred the CETP transgene (CETPTg) into the PLTP0 background. Using an
      in vivo assay to measure the transfer of [(3)H]PC from VLDL into HDL or an in
      vitro assay that determined [(3)H]PC transfer from vesicles into HDL, we could
      detect no phospholipid transfer activity in either PLTP0 or CETPTg/PLTP0 mice. On
      a chow diet, HDL-PL, HDL-CE, and HDL-apolipoprotein AI in CETPTg/PLTP0 mice were
      significantly lower than in PLTP0 mice (45 +/- 7 versus 79 +/- 9 mg/dl; 9 +/- 2
      versus 16 +/- 5 mg/dl; and 51 +/- 6 versus 100 +/- 9, arbitrary units,
      respectively). Similar results were obtained on a high fat, high cholesterol
      diet. These results indicate 1) that there is no redundancy in function of PLTP
      and CETP in vivo and 2) that the combination of the CETP transgene with PLTP
      deficiency results in an additive lowering of HDL levels, suggesting that the
      phenotype of a human PLTP deficiency state would include reduced HDL levels.

PMID- 10893411
TI  - The correlation of ATP-binding cassette 1 mRNA levels with cholesterol efflux
      from various cell lines.
AB  - Studies show that lipid-free apoA-I stimulates release of cholesterol and
      phospholipid from fibroblasts and macrophages. ATP-binding cassette 1 (ABC1) is
      implicated in this release and has been identified as the genetic defect in
      Tangier disease, evidence that ABC1 is critical to the biogenesis of high density
      lipoprotein. We quantified levels of ABC1 mRNA, protein, and cholesterol efflux
      from J774 mouse macrophages +/- exposure to a cAMP analog. Up-regulating ABC1
      mRNA correlated to increased cholesterol efflux in a dose- and time-dependent
      manner. mRNA levels rose after 15 min of exposure while protein levels rose after
      1 h, with increased efflux 2-4 h post-treatment. In contrast to cells from wild
      type mice, peritoneal macrophages from the Abc1 -/- mouse showed a lower level of
      basal efflux and no increase with cAMP treatment. The stimulation of efflux
      exhibits specificity for apoA-I, high density lipoprotein, and other
      apolipoproteins as cholesterol acceptors, but not for small unilamellar vesicles,
      bile acid micelles, or cyclodextrin. We have studied a number of cell types and
      found that while other cell lines express ABC1 constitutively, only J774 and
      elicited mouse macrophages show a substantial increase of mRNA and efflux with
      cAMP treatment. ApoA-I-stimulated efflux was detected from the majority of cell
      lines examined, independent of treatment.

PMID- 10893413
TI  - Leucine limitation induces autophagy and activation of lysosome-dependent
      proteolysis in C2C12 myotubes through a mammalian target of rapamycin-independent
      signaling pathway.
AB  - Loss of muscle mass usually characterizes different pathologies (sepsis, cancer,
      trauma) and also occurs during normal aging. One reason for muscle wasting
      relates to a decrease in food intake. This study addressed the role of leucine as
      a regulator of protein breakdown in mouse C2C12 myotubes and aimed to determine
      which cellular responses regulate the process. Determination of the rate of
      protein breakdown indicated that leucine is one key regulator of this process in
      myotubes because starvation for this amino acid is responsible for 30-40% of the
      total increase generated by total amino acid starvation. Leucine restriction
      rapidly accelerates the rate of protein breakdown (+11 to 15% (p < 0.001) after 1
      h of starvation) in a dose-dependent manner. By using various inhibitors,
      evidence is provided that acceleration of protein catabolism results mainly from
      an induction of autophagy, activation of lysosome-dependent proteolysis, without
      modification of mRNA levels encoding the lysosomal cathepsins B, L, or D. Those
      results suggest that autophagy is an essential cellular response for increasing
      protein breakdown in muscle following food deprivation. Induction of autophagy
      precedes a decrease in global protein synthesis (-20% to -30% (p < 0.001)) that
      occurs after 3 h of leucine starvation. Inhibition of the mammalian target of
      rapamycin (mTOR) activity does not abolish the effect of leucine starvation and
      the level of phosphorylated ribosomal S6 protein is not affected by leucine
      withdrawal. These latter data provide clear evidence that the mTOR signaling
      pathway is not involved in the mediation of leucine effects on both protein
      synthesis and degradation in C2C12 myotubes.

PMID- 10893414
TI  - Characterization of the histone H1-binding protein, NASP, as a cell cycle
      regulated somatic protein.
AB  - Nuclear autoantigenic sperm protein (NASP), initially described as a highly
      autoimmunogenic testis and sperm-specific protein, is a histone-binding protein
      that is a homologue of the N1/N2 gene expressed in oocytes of Xenopus laevis.
      Here, we report a somatic form of NASP (sNASP) present in all mitotic cells
      examined, including mouse embryonic cells and several mouse and human tissue
      culture cell lines. Affinity chromatography and histone isolation demonstrate
      that NASP from myeloma cells is complexed only with H1, linker histones. Somatic
      NASP is a shorter version of testicular NASP (tNASP) with two deletions in the
      coding region arising from alternative splicing and differs from tNASP in its 5'
      untranslated regions. We examined the relationship between NASP mRNA expression
      and the cell cycle and report that in cultures of synchronized mouse 3T3 cells
      and HeLa cells sNASP mRNA levels increase during S-phase and decline in G(2),
      concomitant with histone mRNA levels. NASP protein levels remain stable in these
      cells but become undetectable in confluent cultures of nondividing CV-1 cells and
      in nonmitotic cells in various body tissues. Expression of sNASP mRNA is
      regulated during the cell cycle and, consistent with a role as a histone
      transport protein, NASP mRNA expression parallels histone mRNA expression.

PMID- 10893415
TI  - The I kappa B kinase (IKK) complex is tripartite and contains IKK gamma but not
      IKAP as a regular component.
AB  - A critical step in the activation of NF-kappa B is the phosphorylation of I kappa
      Bs by the I kappa B kinase (IKK) complex. IKK alpha and IKK beta are the two
      catalytic subunits of the IKK complex and two additional molecules, IKK
      gamma/NEMO and IKAP, have been described as further integral members. We have
      analyzed the function of both proteins for IKK complex composition and NF-kappa B
      signaling. IKAP and IKK gamma belong to distinct cellular complexes. Quantitative
      association of IKK gamma was observed with IKK alpha and IKK beta. In contrast
      IKAP was complexed with several distinct polypeptides. Overexpression of either
      IKK gamma or IKAP blocked tumor necrosis factor alpha induction of an NF-kappa B
      dependent reporter construct, but IKAP in addition affected several NF-kappa B
      independent promoters. Whereas specific down-regulation of IKK gamma protein
      levels by antisense oligonucleotides significantly reduced cytokine-mediated
      activation of the IKK complex and subsequent NF-kappa B activation, a similar
      reduction of IKAP protein levels had no effect on NF-kappa B signaling. Using
      solely IKK alpha, IKK beta, and IKK gamma, we could reconstitute a complex whose
      apparent molecular weight is comparable to that of the endogenous IKK complex. We
      conclude that while IKK gamma is a stoichiometric component of the IKK complex,
      obligatory for NF-kappa B signaling, IKAP is not associated with IKKs and plays
      no specific role in cytokine-induced NF-kappa B activation.

PMID- 10893416
TI  - Crystal structure of pseudomonas aeruginosa lipase in the open conformation. The
      prototype for family I.1 of bacterial lipases.
AB  - The x-ray structure of the lipase from Pseudomonas aeruginosa PAO1 has been
      determined at 2.54 A resolution. It is the first structure of a member of
      homology family I.1 of bacterial lipases. The structure shows a variant of the
      alpha/beta hydrolase fold, with Ser(82), Asp(229), and His(251) as the catalytic
      triad residues. Compared with the "canonical" alpha/beta hydrolase fold, the
      first two beta-strands and one alpha-helix (alphaE) are not present. The absence
      of helix alphaE allows the formation of a stabilizing intramolecular disulfide
      bridge. The loop containing His(251) is stabilized by an octahedrally coordinated
      calcium ion. On top of the active site a lid subdomain is in an open
      conformation, making the catalytic cleft accessible from the solvent region. A
      triacylglycerol analogue is covalently bound to Ser(82) in the active site,
      demonstrating the position of the oxyanion hole and of the three pockets that
      accommodate the sn-1, sn-2, and sn-3 fatty acid chains. The inhibited enzyme can
      be thought to mimic the structure of the tetrahedral intermediate that occurs
      during the acylation step of the reaction. Analysis of the binding mode of the
      inhibitor suggests that the size of the acyl pocket and the size and interactions
      of the sn-2 binding pocket are the predominant determinants of the regio- and
      enantio-preference of the enzyme.

PMID- 10893417
TI  - A conserved motif within the vitamin K-dependent carboxylase gene is widely
      distributed across animal phyla.
AB  - The vitamin K-dependent gamma-glutamyl carboxylase catalyzes the
      posttranslational conversion of glutamic acid to gamma-carboxyglutamic acid, an
      amino acid critical to the function of the vitamin K-dependent blood coagulation
      proteins. Given the functional similarity of mammalian vitamin K-dependent
      carboxylases and the vitamin K-dependent carboxylase from Conus textile, a marine
      invertebrate, we hypothesized that structurally conserved regions would identify
      sequences critical to this common functionality. Furthermore, we examined the
      diversity of animal species that maintain vitamin K-dependent carboxylation to
      generate gamma-carboxyglutamic acid. We have cloned carboxylase homologs in full
      length or partial form from the beluga whale (Delphinapterus leucas), toadfish
      (Opsanus tau), chicken (Gallus gallus), hagfish (Myxine glutinosa), horseshoe
      crab (Limulus polyphemus), and cone snail (Conus textile) to compare these
      structures to the known bovine, human, rat, and mouse cDNA sequences. Comparison
      of the predicted amino acid sequences identified a nearly perfectly conserved 38
      amino acid residue region in all of these putative carboxylases. In addition,
      this amino acid motif is also present in the Drosophila genome and identified a
      Drosophila homolog of the gamma-carboxylase. Assay of hagfish liver demonstrated
      vitamin K-dependent carboxylase activity in this hemichordate. These results
      demonstrate the broad distribution of the vitamin K-dependent carboxylase gene,
      including a highly conserved motif that is likely critical for enzyme function.
      The vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid appears to be
      a highly conserved function in the animal kingdom.

PMID- 10893418
TI  - Enhanced activity of a large conductance, calcium-sensitive K+ channel in the
      presence of Src tyrosine kinase.
AB  - Large conductance, calcium-sensitive K(+) channels (BK(Ca) channels) contribute
      to the control of membrane potential in a variety of tissues, including smooth
      muscle, where they act as the target effector for intracellular "calcium sparks"
      and the endothelium-derived vasodilator nitric oxide. Various signal transduction
      pathways, including protein phosphorylation can regulate the activity of BK(Ca)
      channels, along with many other membrane ion channels. In our study, we have
      examined the regulation of BK(Ca) channels by the cellular Src gene product
      (cSrc), a soluble tyrosine kinase that has been implicated in the regulation of
      both voltage- and ligand-gated ion channels. Using a heterologous expression
      system, we observed that co-expression of murine BK(Ca) channel and the human
      cSrc tyrosine kinase in HEK 293 cells led to a calcium-sensitive enhancement of
      BK(Ca) channel activity in excised membrane patches. In contrast, co-expression
      with a catalytically inactive cSrc mutant produced no change in BK(Ca) channel
      activity, demonstrating the requirement for a functional cSrc molecule.
      Furthermore, we observed that BK(Ca) channels underwent direct tyrosine
      phosphorylation in cells co-transfected with BK(Ca) channels and active cSrc but
      not in cells co-transfected with the kinase inactive form of the enzyme. A single
      Tyr to Phe substitution in the C-terminal half of the channel largely prevented
      this observed phosphorylation. Given that cSrc may become activated by receptor
      tyrosine kinases or G-protein-coupled receptors, these findings suggest that cSrc
      dependent tyrosine phosphorylation of BK(Ca) channels in situ may represent a
      novel regulatory mechanism for altering membrane potential and calcium entry.

PMID- 10893419
TI  - Degradation of HIV-1 integrase by the N-end rule pathway.
AB  - Human immunodeficiency virus type-1 (HIV-1) integrase catalyzes the irreversible
      insertion of the viral genome into host chromosomal DNA. We have developed a
      mammalian expression system for the synthesis of authentic HIV-1 integrase in the
      absence of other viral proteins. Integrase, which bears a N-terminal
      phenylalanine, was found to be a short-lived protein in human embryo kidney 293T
      cells. The degradation of integrase could be suppressed by proteasome inhibitors.
      N-terminal phenylalanine is recognized as a degradation signal by a ubiquitin
      proteasome proteolytic system known as the N-end rule pathway. The replacement of
      N-terminal phenylalanine with methionine, valine, or glycine, which are
      stabilizing residues in the N-end rule, resulted in metabolically stabilized
      integrase proteins (half-life of N-terminal Met-integrase was at least 3 h).
      Conversely, the substitution of N-terminal phenylalanine with other destabilizing
      residues retained the metabolic instability of integrase. These findings indicate
      that the HIV-1 integrase is a physiological substrate of the N-end rule. We
      discuss a possible functional similarity to the better understood turnover of the
      bacteriophage Mu transposase and functions of integrase instability to the
      maintenance and integrity of the host cell genome.

PMID- 10893420
TI  - Phosphorylation of p22phox is mediated by phospholipase D-dependent and 
      independent mechanisms. Correlation of NADPH oxidase activity and p22phox
      phosphorylation.
AB  - Human neutrophils participate in the host innate immune response, partly mediated
      by the multicomponent superoxide-generating enzyme NADPH oxidase. A correlation
      between phosphorylation of cytosolic NADPH oxidase components and enzyme
      activation has been identified but is not well understood. We previously showed
      that p22(phox), the small subunit of the membrane-bound oxidase component
      flavocytochrome b(558), is an in vitro substrate for both a phosphatidic acid
      activated kinase and conventional protein kinase C isoforms (Regier, D. S.,
      Waite, K. A., Wallin, R., and McPhail, L. C. (1999) J. Biol. Chem. 274, 36601
      36608). Here we show that several neutrophil agonists (phorbol myristate acetate,
      opsonized zymosan, and N-formyl-methionyl-leucyl-phenylalanine) induce p22(phox)
      phosphorylation in intact neutrophils. To determine if phospholipase D (PLD) is
      needed for p22(phox) phosphorylation, cells were pretreated with ethanol, which
      reduces phosphatidic acid production by PLD in stimulated cells. Phorbol
      myristate acetate-induced phosphorylation of p22(phox) and NADPH oxidase activity
      were not reduced by ethanol. In contrast, ethanol reduced both activities when
      cells were stimulated by N-formyl-methionyl-leucyl-phenylalanine or opsonized
      zymosan. Varying the time of stimulation with opsonized zymosan showed that the
      phosphorylation of p22(phox) coincides with NADPH oxidase activation. GF109203X,
      an inhibitor of protein kinase C and the phosphatidic acid-activated protein
      kinase, decreased both p22(phox) phosphorylation and NADPH oxidase activity in
      parallel in opsonized zymosan-stimulated cells. Stimulus-induced phosphorylation
      of p22(phox) was on Thr residue(s), in agreement with in vitro results. Overall,
      these data show that NADPH oxidase activity and p22(phox) phosphorylation are
      correlated and suggest two mechanisms (PLD-dependent and -independent) by which
      p22(phox) phosphorylation occurs.

PMID- 10893421
TI  - Overproduction of acetyl-CoA carboxylase activity increases the rate of fatty
      acid biosynthesis in Escherichia coli.
AB  - Acetyl-CoA carboxylase (ACC) catalyzes the first committed step of the fatty acid
      synthetic pathway. Although ACC has often been proposed to be a major rate
      controlling enzyme of this pathway, no direct tests of this proposal in vivo have
      been reported. We have tested this proposal in Escherichia coli. The genes
      encoding the four subunits of E. coli ACC were cloned in a single plasmid under
      the control of a bacteriophage T7 promoter. Upon induction of gene expression,
      the four ACC subunits were overproduced in equimolar amounts. Overproduction of
      the proteins resulted in greatly increased ACC activity with a concomitant
      increase in the intracellular level of malonyl-CoA. The effects of ACC
      overexpression on the rate of fatty acid synthesis were examined in the presence
      of a thioesterase, which provided a metabolic sink for fatty acid overproduction.
      Under these conditions ACC overproduction resulted in a 6-fold increase in the
      rate of fatty acid synthesis.

PMID- 10893422
TI  - E3KARP mediates the association of ezrin and protein kinase A with the cystic
      fibrosis transmembrane conductance regulator in airway cells.
AB  - Although it is generally recognized that cystic fibrosis transmembrane
      conductance regulator (CFTR) contains a PSD-95/Disc-large/ZO-1 (PDZ)-binding
      motif at its COOH terminus, the identity of the PDZ domain protein(s) that
      interact with CFTR is uncertain, and the functional impact of this interaction is
      not fully understood. By using human airway epithelial cells, we show that CFTR
      associates with Na(+)/H(+) exchanger (NHE) type 3 kinase A regulatory protein
      (E3KARP), an EBP50/NHE regulatory factor (NHERF)-related PDZ domain protein. The
      PDZ binding motif located at the COOH terminus of CFTR interacts preferentially
      with the second PDZ domain of E3KARP, with nanomolar affinity. In contrast to
      EBP50/NHERF, E3KARP is predominantly localized (>95%) in the membrane fractions
      of Calu-3 and T84 cells, where CFTR is located. Moreover, confocal
      immunofluorescence microscopy of polarized Calu-3 monolayers shows that E3KARP
      and CFTR are co-localized at the apical membrane domain. We also found that ezrin
      associates with E3KARP in vivo. Co-expression of CFTR with E3KARP and ezrin in
      Xenopus oocytes potentiated cAMP-stimulated CFTR Cl(-) currents. These results
      support the concept that E3KARP functions as a scaffold protein that links CFTR
      to ezrin. Since ezrin has been shown previously to function as a protein kinase A
      anchoring protein, we suggest that one function served by the interaction of
      E3KARP with both ezrin and CFTR is to localize protein kinase A in the vicinity
      of the R-domain of CFTR. Since ezrin is also an actin-binding protein, the
      formation of a CFTR.E3KARP.ezrin complex may be important also in stabilizing
      CFTR at the apical membrane domain of airway cells.

PMID- 10893423
TI  - 1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and
      phospholipase A2 activities.
AB  - This report provides definitive evidence that the protein 1-Cys peroxiredoxin is
      a bifunctional ("moonlighting") enzyme with two distinct active sites. We have
      previously shown that human, rat, and bovine lungs contain an acidic Ca(2+)
      independent phospholipase A(2) (aiPLA(2)). The cDNA encoding aiPLA(2) was found
      to be identical to that of a non-selenium glutathione peroxidase (NSGPx). Protein
      expressed using a previously reported E. coli construct which has a His-tag and
      50 additional amino acids at the NH(2) terminus, did not exhibit aiPLA(2)
      activity. A new construct which contains the His-tag plus two extra amino acids
      at the COOH terminus when expressed in Escherichia coli generated a protein that
      hydrolyzed the sn-2 acyl chain of phospholipids at pH 4, and exhibited NSGPx
      activity with H(2)O(2) at pH 8. The expressed 1-Cys peroxiredoxin has identical
      functional properties to the native lung enzyme: aiPLA(2) activity is inhibited
      by the serine protease inhibitor, diethyl p-nitrophenyl phosphate, by the
      tetrahedral mimic 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol
      (MJ33), and by 1-Cys peroxiredoxin monoclonal antibody (mAb) 8H11 but these
      agents have no effect on NSGPx activity; NSGPx activity is inhibited by
      mercaptosuccinate and by 1-Cys peroxiredoxin mAb 8B3 antibody which have no
      effect on aiPLA(2) activity. Mutation of Ser(32) to Ala abolishes aiPLA(2)
      activity, yet the NSGPx activity remains unaffected; a Cys(47) to Ser mutant is
      devoid of peroxidase activity but aiPLA(2) activity remains intact. These results
      suggest that Ser(32) in the GDSWG consensus sequence provides the catalytic
      nucleophile for the hydrolase activity of aiPLA(2), while Cys(47) in the PVCTTE
      consensus sequence is at the active site for peroxidase activity. The
      bifunctional catalytic properties of 1-Cys peroxiredoxin are compatible with a
      simultaneous role for the protein in the regulation of phospholipid turnover as
      well as in protection against oxidative injury.

PMID- 10893424
TI  - A hormone response element in the human apolipoprotein CIII (ApoCIII) enhancer is
      essential for intestinal expression of the ApoA-I and ApoCIII genes and
      contributes to the hepatic expression of the two linked genes in transgenic mice.
AB  - We have generated transgenic mice carrying wild-type promoters of the human
      apolipoprotein A-I (apoA-I)-apoCIII gene cluster or promoters mutated in their
      hormone response elements. The wild-type cluster directed high levels of apoA-I
      gene expression in liver and intestine, moderate expression in kidney, and low to
      minimal expression in other tissues. It also directed high levels of
      chloramphenicol acetyltransferase (CAT) expression (used as a reporter for the
      apoCIII gene) in liver, low levels in intestine and kidney, and no expression in
      other tissues. Mutations in the apoCIII promoter and enhancer abolished the
      intestinal and renal expression of the apoA-I gene, reduced hepatic apoA-I
      expression by 80%, and abolished CAT expression in all tissues. A similar pattern
      of expression was obtained by mutations in the apoCIII enhancer alone. Mutations
      in the proximal apoA-I promoter reduced by 85% hepatic and intestinal apoA-I
      expression and did not affect CAT expression. The findings suggest that a hormone
      response element within the apoCIII enhancer is essential for intestinal and
      renal expression of apoA-I and apoCIII genes and also enhances hepatic
      expression. The hormone response elements of the proximal apoA-I promoter or the
      apoCIII enhancer can promote independently low levels of hepatic and intestinal
      expression of the apoA-I gene in vivo.

PMID- 10893425
TI  - Cloning, genomic organization, and characterization of a human
      cholinephosphotransferase.
AB  - A cholinephosphotransferase activity catalyzes the final step in the de novo
      synthesis of phosphatidylcholine via the transfer of a phosphocholine moiety from
      CDP choline to diacylglycerol. Ethanolaminephosphotransferase activity catalyzes
      a similar reaction substituting CDP ethanolamine as the phosphobase donor. We
      report the identification and cloning of a human cDNA (human
      cholinephosphotransferase (hCPT1)) that codes for a cholinephosphotransferase
      specific enzyme. This was demonstrated using in vitro enzyme assays and in vivo
      measurement of the reconstitution of the phosphatidylcholine and
      phosphatidylethanolamine biosynthetic pathways in yeast cells devoid of their own
      endogenous cholinephosphotransferase and ethanolaminephosphotransferase
      activities. This contrasted with our previously cloned human
      choline/ethanolaminephosphotransferase cDNA that was demonstrated to code for a
      dual specificity choline/ethanolaminephosphotransferase. The hCPT1 and human
      choline/ethanolaminephosphotransferase (hCEPT1) predicted amino acid sequences
      possessed 60% overall identity and had only one variation in the amino acid
      residues within the CDP-alcohol phosphotransferase catalytic motif. In vitro
      assessment of hCPT1 and hCEPT1 derived cholinephosphotransferase activities also
      revealed differences in diradylglycerol specificities including their capacity to
      synthesize platelet-activating factor and platelet-activating factor precursor.
      Expression of the hCPT1 mRNA varied greater than 100-fold between tissues and was
      most abundant in testis followed by colon, small intestine, heart, prostate, and
      spleen. This was in marked contrast to the hCEPT1 mRNA, which has been found in
      similar abundance in all tissues tested to date. Both the hCPT1 and hCEPT1
      enzymes were able to reconstitute the synthesis of PC in yeast to levels provided
      by the endogenous yeast cholinephosphotransferase; however, only hCEPT1-derived
      activity was able to complement the yeast CPT1 gene in its interaction with SEC14
      and affect cell growth.

PMID- 10893426
TI  - Subsite mapping of Aspergillus niger endopolygalacturonase II by site-directed
      mutagenesis.
AB  - To assess the subsites involved in substrate binding in Aspergillus niger
      endopolygalacturonase II, residues located in the potential substrate binding
      cleft stretching along the enzyme from the N to the C terminus were subjected to
      site-directed mutagenesis. Mutant enzymes were characterized with respect to
      their kinetic parameters using polygalacturonate as a substrate and with respect
      to their mode of action using oligogalacturonates of defined length (n = 3-6). In
      addition, the effect of the mutations on the hydrolysis of pectins with various
      degrees of esterification was studied. Based on the results obtained with enzymes
      N186E and D282K it was established that the substrate binds with the nonreducing
      end toward the N terminus of the enzyme. Asn(186) is located at subsite -4, and
      Asp(282) is located at subsite +2. The mutations D183N and M150Q, both located at
      subsite -2, affected catalysis, probably mediated via the sugar residue bound at
      subsite -1. Tyr(291), located at subsite +1 and strictly conserved among
      endopolygalacturonases appeared indispensable for effective catalysis. The
      mutations E252A and Q288E, both located at subsite +2, showed only slight effects
      on catalysis and mode of action. Tyr(326) is probably located at the imaginary
      subsite +3. The mutation Y326L affected the stability of the enzyme. For mutant
      E252A, an increased affinity for partially methylesterified substrates was
      recorded. Enzyme N186E displayed the opposite behavior; the specificity for
      completely demethylesterified regions of substrate, already high for the native
      enzyme, was increased. The origin of the effects of the mutations is discussed.

PMID- 10893427
TI  - Transport of milk constituents by the mammary gland.
AB  - This review deals with the cellular mechanisms that transport milk constituents
      or the precursors of milk constituents into, out of, and across the mammary
      secretory cell. The various milk constituents are secreted by different
      intracellular routes, and these are outlined, including the paracellular pathway
      between interstitial fluid and milk that is present in some physiological states
      and in some species throughout lactation. Also considered are the in vivo and in
      vitro methods used to study mammary transport and secretory mechanisms. The main
      part of the review addresses the mechanisms responsible for uptake across the
      basolateral cell membrane and, in some cases, for transport into the Golgi
      apparatus and for movement across the apical membrane of sodium, potassium,
      chloride, water, phosphate, calcium, citrate, iodide, choline, carnitine,
      glucose, amino acids and peptides, and fatty acids. Recent work on the control of
      these processes, by volume-sensitive mechanisms for example, is emphasized. The
      review points out where future work is needed to gain an overall view of milk
      secretion, for example, in marsupials where milk composition changes markedly
      during development of the young, and particularly on the intracellular
      coordination of the transport processes that result in the production of milk of
      relatively constant composition at a particular stage of lactation in both
      placental and marsupial mammals.

PMID- 10893428
TI  - Role of the basal ganglia in the control of purposive saccadic eye movements.
AB  - In addition to their well-known role in skeletal movements, the basal ganglia
      control saccadic eye movements (saccades) by means of their connection to the
      superior colliculus (SC). The SC receives convergent inputs from cerebral
      cortical areas and the basal ganglia. To make a saccade to an object
      purposefully, appropriate signals must be selected out of the cortical inputs, in
      which the basal ganglia play a crucial role. This is done by the sustained
      inhibitory input from the substantia nigra pars reticulata (SNr) to the SC. This
      inhibition can be removed by another inhibition from the caudate nucleus (CD) to
      the SNr, which results in a disinhibition of the SC. The basal ganglia have
      another mechanism, involving the external segment of the globus pallidus and the
      subthalamic nucleus, with which the SNr-SC inhibition can further be enhanced.
      The sensorimotor signals carried by the basal ganglia neurons are strongly
      modulated depending on the behavioral context, which reflects working memory,
      expectation, and attention. Expectation of reward is a critical determinant in
      that the saccade that has been rewarded is facilitated subsequently. The
      interaction between cortical and dopaminergic inputs to CD neurons may underlie
      the behavioral adaptation toward purposeful saccades.

PMID- 10893429
TI  - Corticotropin releasing hormone and proopiomelanocortin involvement in the
      cutaneous response to stress.
AB  - The skin is a known target organ for the proopiomelanocortin (POMC)-derived
      neuropeptides alpha-melanocyte stimulating hormone (alpha-MSH), beta-endorphin,
      and ACTH and also a source of these peptides. Skin expression levels of the POMC
      gene and POMC/corticotropin releasing hormone (CRH) peptides are not static but
      are determined by such factors as the physiological changes associated with hair
      cycle (highest in anagen phase), ultraviolet radiation (UVR) exposure, immune
      cytokine release, or the presence of cutaneous pathology. Among the cytokines,
      the proinflammatory interleukin-1 produces important upregulation of cutaneous
      levels of POMC mRNA, POMC peptides, and MSH receptors; UVR also stimulates
      expression of all the components of the CRH/POMC system including expression of
      the corresponding receptors. Molecular characterization of the cutaneous POMC
      gene shows mRNA forms similar to those found in the pituitary, which are
      expressed together with shorter variants. The receptors for POMC peptides
      expressed in the skin are functional and include MC1, MC5 and mu-opiate, although
      most predominant are those of the MC1 class recognizing MSH and ACTH. Receptors
      for CRH are also present in the skin. Because expression of, for example, the MC1
      receptor is stimulated in a similar dose-dependent manner by UVR, cytokines, MSH
      peptides or melanin precursors, actions of the ligand peptides represent a
      stochastic (predictable) nonspecific response to environmental/endogenous
      stresses. The powerful effects of POMC peptides and probably CRH on the skin
      pigmentary, immune, and adnexal systems are consistent with stress-neutralizing
      activity addressed at maintaining skin integrity to restrict disruptions of
      internal homeostasis. Hence, cutaneous expression of the CRH/POMC system is
      highly organized, encoding mediators and receptors similar to the hypothalamic
      pituitary-adrenal (HPA) axis. This CRH/POMC skin system appears to generate a
      function analogous to the HPA axis, that in the skin is expressed as a highly
      localized response which neutralizes noxious stimuli and attendant immune
      reactions.

PMID- 10893430
TI  - Retinoids in embryonal development.
AB  - The key role of vitamin A in embryonal development is reviewed. Special emphasis
      is given to the physiological action of retinoids, as evident from the retinoid
      ligand knockout models. Retinoid metabolism in embryonic tissues and teratogenic
      consequences of retinoid administration at high doses are presented.
      Physiological and pharmacological actions of retinoids are outlined and explained
      on the basis of their interactions as ligands of the nuclear retinoid receptors.
      Immediate target genes and the retinoid response elements of their promoters are
      summarized. The fundamental role of homeobox genes in embryonal development and
      the actions of retinoids on their expression are discussed. The similarity of the
      effects of retinoid ligand knockouts to effects of compound retinoid receptor
      knockouts on embryogenesis is presented. Although much remains to be clarified,
      the emerging landscape offers exciting views for future research.

PMID- 10893431
TI  - Exercise and the immune system: regulation, integration, and adaptation.
AB  - Stress-induced immunological reactions to exercise have stimulated much research
      into stress immunology and neuroimmunology. It is suggested that exercise can be
      employed as a model of temporary immunosuppression that occurs after severe
      physical stress. The exercise-stress model can be easily manipulated
      experimentally and allows for the study of interactions between the nervous, the
      endocrine, and the immune systems. This review focuses on mechanisms underlying
      exercise-induced immune changes such as neuroendocrinological factors including
      catecholamines, growth hormone, cortisol, beta-endorphin, and sex steroids. The
      contribution of a metabolic link between skeletal muscles and the lymphoid system
      is also reviewed. The mechanisms of exercise-associated muscle damage and the
      initiation of the inflammatory cytokine cascade are discussed. Given that
      exercise modulates the immune system in healthy individuals, considerations of
      the clinical ramifications of exercise in the prevention of diseases for which
      the immune system has a role is of importance. Accordingly, drawing on the
      experimental, clinical, and epidemiological literature, we address the
      interactions between exercise and infectious diseases as well as exercise and
      neoplasia within the context of both aging and nutrition.

PMID- 10893432
TI  - Molecular analysis of the sodium/iodide symporter: impact on thyroid and
      extrathyroid pathophysiology.
AB  - The Na(+)/I(-) symporter (NIS) is an intrinsic membrane protein that mediates the
      active transport of iodide into the thyroid and other tissues, such as salivary
      glands, gastric mucosa, and lactating mammary gland. NIS plays key roles in
      thyroid pathophysiology as the route by which iodide reaches the gland for
      thyroid hormone biosynthesis and as a means for diagnostic scintigraphic imaging
      and for radioiodide therapy in hyperthyroidism and thyroid cancer. The molecular
      characterization of NIS started with the 1996 isolation of a cDNA encoding rat
      NIS and has since continued at a rapid pace. Anti-NIS antibodies have been
      prepared and used to study NIS topology and its secondary structure. The
      biogenesis and posttranslational modifications of NIS have been examined, a
      thorough electrophysiological analysis of NIS has been conducted, the cDNA
      encoding human NIS (hNIS) has been isolated, the genomic organization of hNIS has
      been elucidated, the regulation of NIS by thyrotropin and I(-) has been analyzed,
      the regulation of NIS transcription has been studied, spontaneous NIS mutations
      have been identified as causes of congenital iodide transport defect resulting in
      hypothyroidism, the roles of NIS in thyroid cancer and thyroid autoimmune disease
      have been examined, and the expression and regulation of NIS in extrathyroidal
      tissues have been investigated. In gene therapy experiments, the rat NIS gene has
      been transduced into various types of human cells, which then exhibited active
      iodide transport and became susceptible to destruction with radioiodide. The
      continued molecular analysis of NIS clearly holds the potential of an even
      greater impact on a wide spectrum of fields, ranging from structure/function of
      transport proteins to the diagnosis and treatment of cancer, both in the thyroid
      and beyond.

PMID- 10893433
TI  - Creatine and creatinine metabolism.
AB  - The goal of this review is to present a comprehensive survey of the many
      intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the
      pathways and regulation of Cr biosynthesis and degradation, species and tissue
      distribution of the enzymes and metabolites involved, and of the inherent
      implications for physiology and human pathology. Very recently, a series of new
      discoveries have been made that are bound to have distinguished implications for
      bioenergetics, physiology, human pathology, and clinical diagnosis and that
      suggest that deregulation of the creatine kinase (CK) system is associated with a
      variety of diseases. Disturbances of the CK system have been observed in muscle,
      brain, cardiac, and renal diseases as well as in cancer. On the other hand, Cr
      and Cr analogs such as cyclocreatine were found to have antitumor, antiviral, and
      antidiabetic effects and to protect tissues from hypoxic, ischemic,
      neurodegenerative, or muscle damage. Oral Cr ingestion is used in sports as an
      ergogenic aid, and some data suggest that Cr and creatinine may be precursors of
      food mutagens and uremic toxins. These findings are discussed in depth, the
      interrelationships are outlined, and all is put into a broader context to provide
      a more detailed understanding of the biological functions of Cr and of the CK
      system.

PMID- 10893434
TI  - Calcium ion in skeletal muscle: its crucial role for muscle function, plasticity,
      and disease.
AB  - Mammalian skeletal muscle shows an enormous variability in its functional
      features such as rate of force production, resistance to fatigue, and energy
      metabolism, with a wide spectrum from slow aerobic to fast anaerobic physiology.
      In addition, skeletal muscle exhibits high plasticity that is based on the
      potential of the muscle fibers to undergo changes of their cytoarchitecture and
      composition of specific muscle protein isoforms. Adaptive changes of the muscle
      fibers occur in response to a variety of stimuli such as, e.g., growth and
      differentition factors, hormones, nerve signals, or exercise. Additionally, the
      muscle fibers are arranged in compartments that often function as largely
      independent muscular subunits. All muscle fibers use Ca(2+) as their main
      regulatory and signaling molecule. Therefore, contractile properties of muscle
      fibers are dependent on the variable expression of proteins involved in Ca(2+)
      signaling and handling. Molecular diversity of the main proteins in the Ca(2+)
      signaling apparatus (the calcium cycle) largely determines the contraction and
      relaxation properties of a muscle fiber. The Ca(2+) signaling apparatus includes
      1) the ryanodine receptor that is the sarcoplasmic reticulum Ca(2+) release
      channel, 2) the troponin protein complex that mediates the Ca(2+) effect to the
      myofibrillar structures leading to contraction, 3) the Ca(2+) pump responsible
      for Ca(2+) reuptake into the sarcoplasmic reticulum, and 4) calsequestrin, the
      Ca(2+) storage protein in the sarcoplasmic reticulum. In addition, a multitude of
      Ca(2+)-binding proteins is present in muscle tissue including parvalbumin,
      calmodulin, S100 proteins, annexins, sorcin, myosin light chains, beta-actinin,
      calcineurin, and calpain. These Ca(2+)-binding proteins may either exert an
      important role in Ca(2+)-triggered muscle contraction under certain conditions or
      modulate other muscle activities such as protein metabolism, differentiation, and
      growth. Recently, several Ca(2+) signaling and handling molecules have been shown
      to be altered in muscle diseases. Functional alterations of Ca(2+) handling seem
      to be responsible for the pathophysiological conditions seen in
      dystrophinopathies, Brody's disease, and malignant hyperthermia. These also
      underline the importance of the affected molecules for correct muscle
      performance.

PMID- 10893435
TI  - Transduction effect of antisense K-ras on malignant phenotypes in gastric cancer
      cells.
AB  - The antitumoral effects of antisense RNA to K-ras were investigated in gastric
      cancer cell lines by examining the level of K-ras expression and the
      tumorigenicity in vitro and in vivo. Polymerase chain reaction-single strand
      conformation polymorphism (PCR-SSCP), DNA sequencing, and immunoblotting analysis
      revealed that YCC-1 gastric cancer cells overexpressed wild type K-ras, whereas
      YCC-2 cells had a homozygous mutation in codon 12 from GGT (glycine) to AGT
      (serine), while SNU-1 cells had a heterozygous mutation to GAT (asparagine) in
      the identical position. Both YCC-1 and YCC-2 cells were transduced by LNC-AS/K
      ras containing the antisense 2.2 kb genomic K-ras DNA fragment covering exon 2
      and exon 3 specific for K-ras. The application of antisense K-ras significantly
      downregulated the expression of K-ras and had no influence on the expression of
      either H-ras or N-ras. The antisense-transduced YCC-2 cells grew considerably
      slower than the control group transduced by LNCX, whereas the growth inhibition
      of antisense-transduced YCC-1 cells was less prominent than that of transduced
      YCC-2 cells. In addition, the tumorigenicity of YCC-2 cells transduced by LNC
      AS/K-ras was totally lost. Therefore, our results imply that the specific
      inhibition of K-ras p21 protein can be accomplished by introducing the antisense
      covering the K-ras- specific region to gastric cancer cells with aberrant K-ras
      expression, resulting in a reduction of the growth rate and suppression of
      tumorigenicity.

PMID- 10893436
TI  - Suppressive effect of the herbal medicine Oren-gedoku-to on cyclooxygenase-2
      activity and azoxymethane-induced aberrant crypt foci development in rats.
AB  - The present study is part of a program to obtain effective chemopreventive agents
      with low toxicity from medicinal herbs and traditional herbal medicines. We
      previously reported that Oren (Coptidis rhizoma) and Ogon (Scutellariae radix)
      inhibit azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation. In the
      present investigation, we found Sanshishi (Gardeniae fructus) and the traditional
      herbal medicine Oren-gedoku-to (OGT), composed of Ogon, Oren, Sanshishi and
      Obaku, also have preventive potential. Sanshishi and OGT decreased the numbers of
      ACF to 25.2 and 59.4% of the control value at 2% in the diet, respectively.
      Adverse effects, evidenced by body weight loss, were weaker with OGT than
      component herbs. To investigate their mechanisms of action, the influence on
      cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activities was studied.
      Both OGT and Sanshishi inhibited COX-2 but not COX-1, this presumably
      contributing to their suppressive effects on ACF development. The results suggest
      that OGT may be useful for colon cancer chemoprevention in terms of efficacy and
      toxicity.

PMID- 10893437
TI  - Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in
      F344 rats.
AB  - The modifying effects of dietary administration of ferulic acid (FA) on
      azoxymethane (AOM)-induced colon carcinogenesis were examined in three
      experiments with male 344 rats. In the first experiment, the modifying effect of
      FA on AOM (15 mg/kg body weight, once a week, for 3 weeks)-induced formation of
      aberrant crypt foci (ACF) was examined in five groups. Numbers of ACF/colon of
      groups 2 (AOM+250 ppm FA) and 3 (AOM+500 ppm FA) at the termination (5 weeks
      after the start) were smaller than of group 1 (AOM alone). Those of ACF/cm(2) of
      group 3 were also smaller than of group 1 (P<0.05). In the second experiment, a
      long-term assay for the effects of FA was conducted with seven groups. At the
      termination (35 weeks), groups 2 and 3 which were given FA during the initiation
      phase at doses of 250 and 500 ppm, respectively, had lower incidences of colonic
      carcinomas (23 and 27%, respectively) than group 1 which was given AOM alone
      (59%; P<0.05). In the third experiment, to determine whether FA could modify the
      activities of phase II detoxifying enzymes, glutathione S-transferase (GST) and
      quinone reductase (QR) in liver and colon, 60 rats were gavaged with FA at four
      doses (0, 25, 50, 100 mg/kg body weight). Dosing of 100 mg/kg significantly
      elevated GST activity in liver (P<0.03), and QR activities in liver and colonic
      mucosa (P<0.01 and P<0.02, respectively), suggesting that detoxifying enzymes are
      related to the blocking effect of FA on AOM-induced colon carcinogenesis.

PMID- 10893438
TI  - Apicidin, an inhibitor of histone deacetylase, prevents H-ras-induced invasive
      phenotype.
AB  - Cancer metastasis represents the most important cause of cancer death and agents
      that may inhibit tumor cell invasion have been extensively pursued. In the
      present study, we have examined the anti-invasive effect of apicidin [cyclo(N-O
      methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl -L-2-amin o-8-oxodecanoyl)], a
      fungal metabolite that was identified as an antiprotozoal agent known to inhibit
      parasite histone deacetylase (HDAC). We show that apicidin significantly inhibits
      H-ras-induced invasive phenotype of MCF10A human breast epithelial cells in
      parallel with a specific downregulation of matrix metalloproteinase (MMP)-2, but
      not MMP-9. We also show that apicidin induces a morphological reversal and growth
      inhibition of H-ras MCF10A cells similar to that induced by other HDAC
      inhibitors. Taken in conjunction with the fact that uncontrolled ras activation
      is probably the most common genetic defect in human cancer cells, our data
      showing the anti-invasive and detransforming activities of apicidin in H-ras
      transformed MCF10A cells may suggest a potential use of HDAC inhibitors for
      treatment of cancer.

PMID- 10893439
TI  - Restoration of gap junctional intercellular communication by caffeic acid
      phenethyl ester (CAPE) in a ras-transformed rat liver epithelial cell line.
AB  - Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis,
      has been identified as having anti-inflammatory, anti-viral and anti-cancer
      properties. Since the deficiency of gap junctional intercellular communication
      (GJIC) has been shown to be a characteristic of most cancer cells, this study was
      designed to test the hypothesis that the anti-carcinogenic activity of CAPE might
      be related to its ability to restore GJIC in tumorigenic GJIC-deficient cells (WB
      ras2 cells). The results showed that CAPE restored GJIC, phosphorylation of
      connexin 43 (Cx43) and its normal localization on the plasma membrane in WB-ras2
      cells after 3 days at 5 microg/ml concentration. Additionally, CAPE inhibited
      growth in soft agar and decreased the protein level of p21(ras). The results are
      consistent with the hypothesis that the anti-cancer mechanism of CAPE may be
      mediated by its ability to restore GJIC.

PMID- 10893440
TI  - Inhibition of phthalocyanine-sensitized photohemolysis of human erythrocytes by
      polyphenolic antioxidants: description of quantitative structure-activity
      relationships.
AB  - Polyphenolic antioxidants protected against Al-phthalocyanine tetrasulfonate
      sensitized photohemolysis of human erythrocytes. A quantitative structure
      activity relationship has been obtained to describe the protective effects of di-
      and trihydroxybenzenes: log cI(50) (microM)=(1.8620+/-1.5565)+(3.6366+/-2.8245)
      E(1)(7) (V)-(0. 4034+/-0.0765) log P (r(2)=0.8367), where cI(50) represents the
      concentrations of compounds for the 2-fold increase in the lag-phase of
      hemolysis, E(1)(7) represents the compound single-electron oxidation potential,
      and P represents the octanol/water partition coefficient. The cI(50) for
      quercetin and taxifolin were close, and cI(50) for morin, kaempferol and
      hesperetin were lower than might be predicted by this equation. The protection
      from hemolysis by azide, a quencher of singlet oxygen ((1)O(2)) was accompanied
      by increase in cI(50) of polyphenols, indicating that azide and polyphenols
      competed for the same damaging species, (1)O(2). These findings point out to two
      factors, determining the protective efficiency of polyphenols against (1)O(2),
      namely, ease of electron donation and lipophilicity.

PMID- 10893441
TI  - Carcinoembryonic antigen family of adhesion molecules in the cotton top tamarin
      (Saguinus oedipus).
AB  - Humans and the cotton top tamarin, a model for colitis and colorectal cancer,
      share carcinoembryonic antigen (CEA) moieties. We quantified CEA in colonic
      washings and extracts in both, and CEA bands were confirmed by Western blot. We
      compared CEA-family expression in tissues and serum in the tamarin with that of
      the common marmoset, which develops colitis but not cancer. CEA levels are higher
      in tamarin washings compared with humans, and higher than in marmosets extracts
      (P<0.005). CEA molecular species appear to be specific, and human CEA-family
      member epitopes are also found in these primates. The higher CEA levels in the
      tamarin may reflect the overall higher cancer prevalence.

PMID- 10893442
TI  - Role of the MEN1 tumour suppressor gene in human ductal pancreatic cancer.
AB  - MEN1 is a novel tumour suppressor gene involved in the etiology of sporadic
      endocrine pancreatic tumours. Based on common ontogenetic features of both
      tissues, we analyzed the role of MEN1 in ductal pancreatic cancer. Wild type MEN1
      mRNA expression, but no mutations within the MEN1 coding sequence or MEN1
      promoter region were detected in human pancreatic adenocarcinoma tissues and
      carcinoma cell lines, using sensitive single-strand conformational polymorphism
      heteroduplex and sequencing analyses. Thus, human pancreatic cancer does not seem
      to require inactivation of the MEN1 tumour suppressor pathway.

PMID- 10893443
TI  - Immune modulatory potentials of antineoplaston A-10 in breast cancer patients.
AB  - Antineoplastons are naturally occurring cytodifferentiating agents. Chemically,
      they are medium and small sized peptides, amino acid derivatives and organic
      acids, which exist in blood, tissues and urine. Antineoplaston A-10 (3
      phenylacetylamino-2,6-piperidinedione) is the first chemically identified
      antineoplaston. Previously we have shown a strong inverse association of urinary
      antineoplaston A-10 with breast cancer. This study is designed to evaluate
      neutrophil apoptosis in patients with breast cancer at time of diagnosis and to
      correlate urinary antineoplaston A-10 levels with neutrophil apoptosis and to
      describe the direct effect of A-10 in vitro on neutrophil apoptosis in breast
      cancer patients. The participants were patients with a histologically confirmed
      diagnosis of breast cancer. Only those cases without previous treatment for
      breast cancer were included. Neutrophil apoptosis was assessed in breast cancer
      patients both morphologically and by DNA fragmentation and studied relative to
      healthy controls. Antineoplaston A-10 was measured using high performance liquid
      chromatography in urine samples collected from the patients. Urine samples from
      normal women served as controls. Direct effect of antineoplaston A-10 on
      neutrophil apoptosis was tested in vitro after adding A-10 at a concentration of
      10 ng/ml to the cellular suspensions of breast cancer patients. Non-treated
      samples served as controls. Significantly higher neutrophil apoptosis levels were
      detected among patients with breast cancer with a P value <0.001. Urinary
      antineoplaston A-10 level is significantly negatively correlated with high
      apoptosis levels (P<0.0001). In vitro, antineoplaston A-10 was found to inhibit
      significantly the neutrophil apoptosis with a P value <0.0001. These findings
      confirm the presence of immune defects among patients with breast cancer and such
      results should stimulate the development of new strategies to induce and augment
      immunity for the treatment of breast cancer. Antineoplaston A-10 may provide
      rational basis for designing trials to employ its immune modulatory potentials as
      adjuvant therapy in breast cancer patients.

PMID- 10893444
TI  - Induction of apoptosis by hydrolyzable tannins from Eugenia jambos L. on human
      leukemia cells.
AB  - Eugenia jambos L. (Myrtaceae) is an antipyretic and anti-inflammatory herb of
      Asian folk medicine. A 70% acetone extract exerted the strongest cytotoxic
      effects on human leukemia cells (HL-60) from a preliminary screening of 15
      plants. The cytotoxic principles were separated by bio-assay-guided fractionation
      to HL-60 cells; two hydrolyzable tannins (1-O-galloyl castalagin and casuarinin)
      were isolated from the 70% acetone extract. All significantly inhibited human
      promyelocytic leukemia cell line HL-60 and showed less cytotoxicity to human
      adenocarcinoma cell line SK-HEP-1 and normal cell lines of human lymphocytes and
      Chang liver cells. Thus, these compounds were exhibited the dose-dependent manner
      in HL-60 cells and the IC(50) were 10.8 and 12.5 microM, respectively. Flow
      cytometric analysis demonstrated the presence of apoptotic cells with low DNA
      content, a decrease of cell population at G(2)/M phase, and a concomitant
      increase of cell population at G(1) phase. The apoptosis induced by these two
      compounds was also demonstrated by DNA fragmentation assay and microscopic
      observation. These results suggest that the cytotoxic mechanism of both antitumor
      principle constituents might be the induction of apoptosis in HL-60 cells.

PMID- 10893445
TI  - Suppressive effects of novel ferulic acid derivatives on cellular responses
      induced by phorbol ester, and by combined lipopolysaccharide and interferon
      gamma.
AB  - A total of 23 ferulic acid (FA) derivatives were synthesized, and investigated
      for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate-induced
      Epstein-Barr virus (EBV) activation and superoxide (O(2)(-)) generation. Most of
      the derivatives showed significant EBV activation suppression or cytotoxicity at
      a concentration of 100 microM, with FA15 as the most potent suppressor. In both
      assays, FA6-FA17, bearing straight- or branched-alkyl side chains, exhibited
      marked suppression of O(2)(-) generation, with both FA16 and FA17 being highly
      active, while FA itself was virtually inactive. The activity differences seen
      between FA16/FA17 and FA are attributable, at least in part, to their cellular
      incorporating efficiencies. Further, both FA15 and FA21 attenuated the expression
      of inducible nitric oxide synthase and cyclooxygenase-2 proteins, while FA did
      not. Our results suggest that these novel FA derivatives are effective
      chemopreventive agents.

PMID- 10893446
TI  - Cancer chemopreventive activity of an iridoid glycoside, 8-acetylharpagide, from
      Ajuga decumbens.
AB  - In the course of our continuing search for novel cancer chemopreventive agents
      from natural sources, several kinds of Labiatae plants were screened.
      Consequently, the iridoid glycoside derivative, 8-acetylharpagide (8-AcHarp), was
      obtained from the flowering whole plant of Ajuga decumbens as an active
      constituent. This glycoside exhibited the remarkable inhibitory effect on two
      stage carcinogenesis test of mouse skin tumors induced by nitric oxide (NO)
      donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexen eamide
      (NOR 1) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a
      promoter. Further, 8-AcHarp exhibited potent anti-tumor-promoting activity on two
      stage carcinogenesis test of mouse hepatic tumor using N-nitrosodiethylamine
      (DEN) as an initiator and phenobarbital (PB) as a promoter.

PMID- 10893447
TI  - Identification of microsatellite length polymorphism by a polymerase chain
      reaction-based assay at IL-1beta gene locus in cancer cells.
AB  - It has long been considered that genetic instability is an integral component of
      human neoplasia, however the frequency of microsatellite instability in human
      melanoma and non-melanoma skin cancer was less evidenced. We report here an
      alteration at the complex dinucleotide repeat (TC)n sequence in the interleukin 1
      beta gene locus by polymerase chain reaction (PCR)-based assay in mouse melanoma
      as well as in various cancer cells, which may provide a simple, rapid, non
      radioactive screening assay for cancer detection.

PMID- 10893448
TI  - Lack of effect of the cytokine suppressive agent FR167653 on tumour growth and
      cachexia in rats bearing the Yoshida AH-130 ascites hepatoma.
AB  - Daily s.c. administration of 6 mg/kg of FR167653 (an inhibitor of the synthesis
      of interleukin-1 and tumour necrosis factor-alpha) to rats bearing the ascites
      hepatoma Yoshida AH-130 (a highly cachectic tumour) did not prevent either the
      anorexia or the massive weight loss - affecting both adipose tissue and skeletal
      muscle - present in the cachectic animals. The compound did not affect the
      circulating levels of triacylglycerols or other metabolites such as glucose or
      lactate. Nor did the administration of FR167653 influence tumour growth. It is
      concluded that the drug is unable to reverse the cachectic state in this
      particular experimental tumour model.

PMID- 10893451
TI  - Amblyopia: its treatment today and its portent for the future.

PMID- 10893449
TI  - Administration of wild-type p53 adenoviral vector synergistically enhances the
      cytotoxicity of anti-cancer drugs in human lung cancer cells irrespective of the
      status of p53 gene.
AB  - Recombinant adenovirus mediated p53 gene transfer combined with anti-cancer drugs
      has clinical potential for gene therapy of lung cancer. We constructed a
      recombinant adenoviral vector expressing wild-type p53 cDNA (Ad-p53), and
      assessed the efficacy of a combined treatment with Ad-p53 and six anti-cancer
      drugs (cisplatin, 5-fluorouracil, doxorubicin, docetaxel, irinotecan, and
      etoposide) for human lung cancer cell lines, H1299 (with deleted p53), RERF-LC-OK
      (with mutant p53), and A549 (with wild-type p53). The infection of the Ad-p53
      vector into H1299 cells, RERF-LC-OK cells, or A549 cells increased the
      sensitivity to all six drugs regardless of the cellular p53 status, and a
      synergism was observed by the isobolic method in combination studies (D<1). We
      conclude that our strategy using adenoviral mediated p53 gene transfer to cancer
      cells can enhance the cytotoxic effect of anti-cancer drugs, which leading to an
      improvement of lung cancer chemotherapy.

PMID- 10893452
TI  - On strabismus: superior oblique tendon expanders; surgery for accommodative
      esotropia, etc.

PMID- 10893453
TI  - Results and complications in 66 cases using a silicone tendon expander on
      overacting superior obliques with A- pattern anisotropias.
AB  - PURPOSE: To supplement limited reports in the literature of the results
      (outcome)and complications of this procedure with our own recent experience.
      METHODS: A total of 66 patients with bilateral overaction of the superior oblique
      and A-pattern strabismus plus 5 patients with a unilateral overacting superior
      oblique secondary to inferior oblique palsy were treated with a 7 mm silicone
      expander. RESULTS: The fist group of 66 patients had an average preoperative A
      pattern of 39.6 prism diopters with an average correction of the A-pattern from
      the surgery of 36.3 prism diopters. COMPLICATIONS: Of all 137 operations in these
      71 patients, three patients had a sterile orbital cellulitis postoperatively
      successfully treated with steroids. Also, one patient acquired a Brown's Syndrome
      like condition postop'. In these four patients, the sub-Tenon's capsule space had
      been inadvertently entered during surgery. In addition one unilateral superior
      oblique palsy occurred postoperatively. CONCLUSION: While this procedure has a
      very high success rate, special care should be taken with this surgery to avoid
      entering the sub-Tenon's capsule space.

PMID- 10893454
TI  - Surgical modification of the AC/A ratio and the binocular alignment ("Phoria") at
      distance; its influence on accommodative esotropia: a study of 21 cases.
AB  - PURPOSE: To study these changes in patients and their relation to manifestation
      of accommodative esotropia and response to surgery. METHODS: Patient-subjects: 21
      patients who had difficulty adjusting to spectacle correction and underwent
      bilateral medial rectus loop suspension-recession surgery to alleviate their
      accommodative esotropia. Measurements of AC/A, uncorrected distance phoria, and
      related parameters were taken before and after surgical intervention was
      performed and were analyzed using analysis of variance (ANOVA). RESULTS: Both
      AC/A ratios and the distance phorias are "statistically significantly" (p< or
      =0.05), and independently, reduced by this surgical procedure. The manifestation
      of accommodative esotropia and response to surgery can be fairly accurately
      predicted from the values of AC/A ratio and distance phoria. CONCLUSION: Surgical
      treatment of accommodative esotropia creates well defined, long-lasting
      reductions in the AC/A ratio and the distance phoria.

PMID- 10893455
TI  - Intermittent exotropia: stimulus characteristics affect tests for retinal
      correspondence and suppression.
AB  - BACKGROUND AND PURPOSE: Prior studies have reported various sensory responses in
      subjects with intermittent exotropia [X(T)]. These varying responses have been
      proposed due to differences in stimulus targets, backgrounds, or even a lack of
      control of binocular alignment. This study investigated the effects of varying
      target and background stimuli while controlling binocular alignment. METHODS:
      Eight X(T)s of the divergence excess or basic type were presented dichoptic
      computer generated visual stimuli while an infra red eye movement monitoring
      system determined horizontal eye position of each eye. Target and background were
      varied to assess their effect on sensory responses during latent and manifest
      exotropia. RESULTS: Most of our X(T)s demonstrated, while tropic, a consistent,
      i.e., dominant, type of retinal correspondence, i.e. a response that occurred on
      most tests, independent of the stimulus or background used for testing. Four
      subjects demonstrated harmonious anomalous retinal correspondence (HARC) while
      three subjects demonstrated normal retinal correspondence (NRC) with three out of
      four of the tests. In two out of four stimuli used for testing, one subject
      demonstrated NRC and another HARC. CONCLUSIONS: Complex backgrounds resulted in
      the largest number of suppressions, whereas blank backgrounds decreased the
      number of reported suppressions.

PMID- 10893456
TI  - Retinal nerve fiber layer thickness in human strabismic amblyopia.
AB  - BACKGROUND AND PURPOSE: Amblyopia is characterized by histopathological changes
      in the visual cortex and lateral geniculate nucleus. In the retina, however, no
      abnormalities have yet been reported. The purpose of this study was to compare
      the nerve fiber layer (NFL) thickness in the amblyopic eye with that in the sound
      eye of patients with strabismic amblyopia. As a practical implication, we
      investigated the validity of comparing Nerve Fiber Analyzer (NFA) measurements
      obtained in amblyopic eyes to the normative database built into the NFA. METHODS:
      NFL thickness was measured with a third generation NFA, the GDx (Laser Diagnostic
      Technologies, San Diego, CA). This is a scanning laser polarimeter, designed for
      monitoring glaucoma. The following NFL thickness parameters (all in microns) were
      compared: average thickness, superior maximum, inferior maximum, superior
      average, inferior average, nasal median and temporal median. Twenty patients with
      strabismic amblyopia were imaged with the NFA. Patients had no nystagmus,
      neurological disease or glaucoma. Nine patients had amblyopia in the right eye,
      and 11 patients in the left eye. RESULTS: In general, the sound eyes yielded
      higher thickness measures than the amblyopic eyes. These differences, however,
      were small, averaging only 1.5%, p = 0.6, and therefore not "statistically
      significant" at the p&le 0.05 level. CONCLUSIONS: Using the standard of
      "Statistical Significance = p< or =0.05", when amblyopic eyes are measured with
      the NFA, the built-in normative database may serve as the reference data

PMID- 10893457
TI  - Grand rounds #58: a case of a lost medial rectus in the fixing eye of a patient
      with a face turn secondary to nystagmus.

PMID- 10893458
TI  - Opposition to treatment of traumatic hyphema with antifibrinolytics/steroids.

PMID- 10893459
TI  - Traumatic hyphema management: assuring compliance with outpatient care;
      steroidophobia: rational or irrational?

PMID- 10893460
TI  - Outpatient management of traumatic hyphemas in children.
AB  - OBJECTIVE: There are no outcome reports in the literature for outpatient
      management of traumatic hyphemas in children. Therefore we studied such cases at
      our institutions. DESIGN: Retrospective chart review. PARTICIPANTS: 25 children
      less than 16 years of age with grade I traumatic hyphemas. INTERVENTION:
      Inactivity at home with frequent office visits to monitor progress and
      complications. Treatment otherwise varied but virtually all patients received
      protective eye shields and topical steroids. MAIN OUTCOME MEASURES: Rate of
      rebleeding and final visual acuity. RESULTS: Three patients (12%) suffered a
      rebleed; one required surgery for clot evacuation. One of the three did not
      receive topical steroids and if he is excluded, rebleed rate is 2/24 or 8.3%. The
      hyphema resolved without sequelae in the other 22 patients. All patients had a
      final visual acuity of 20/40 or better except three patients (12%) who had
      concurrent vision-limiting ocular injuries and/or disease. Final visual acuity
      was 20/30 or better in all three patients with rebleeds. CONCLUSIONS: Our rebleed
      rate was within the broad range of rebleed rates reported in the literature.
      However, improved efforts to identify children at highest risk for rebleeding, to
      maximize compliance with treatments, and to consider systemic agents in selected
      cases, could further reduce the rebleed rate and increase acceptance and safety
      of outpatient management in pediatric traumatic hyphemas.

PMID- 10893461
TI  - Traumatic hyphema: a comprehensive review of the past half century yields 8076
      cases for which specific medical treatment reduces rebleeding 62%, from 13% to 5%
      (P<.0001).
AB  - PURPOSE: To eliminate the continuing so-called "controversy" regarding, and
      opposition to, the specific medical management of traumatic hyphema (TH) with
      systemic antifibrinolytic agents including aminocaproic acid (ACA) and tranexamic
      acid (TXA) and steroids (prednisone); to illuminate the role of topical steroids.
      METHOD: Review of all (English language) studies since 1950 of these medical
      treatments of TH, and contemporary no specific medical treatment controls.
      RESULTS: The difference between the average rebleeding rate in the specifically
      medically treated group, 4.89%, and that rate in the untreated group, 13.02%, was
      statistically a true difference due not to chance but to the difference in
      therapy with a probability of <0.0001 by Chi Square Test, Yates Corrected Chi
      Square Test and Fisher's Exact Test. This was also true individually respectively
      and with identical probabilities of p=<0.0001 for systemic steroids, topical
      steroids, ACA and TXA. Combined topical steroids and systemic ACA or TXA did not
      further improve results. CONCLUSION: Preventing rebleeding episodes remains a
      major treatment objective in the clinical management of TH. This is best
      accomplished by the Yasuna systemic steroid No Touch or No Touch PLUS treatment
      protocol, the only treatment protocols consistently yielding zero rebleed rates
      in non-Scandinavian populations.

PMID- 10893462
TI  - Traumatic hyphema: a critical review of the scientifically catastrophic history
      of steroid treatment therefore; and A report of 24 additional cases with no
      rebleeding after treatment with the Yasuna systemic steroid, no touch PLUS
      protocol.
AB  - PURPOSE: To establish a detailed history of steroid therapy administered either
      systemically or topically for traumatic hyphema (TH) over the past 40 years. To
      this literature, we report and add another 24 TH cases treated with the Yasuna
      systemic steroid No Touch PLUS protocol. METHODS: Review of all reports in
      Medline since its inception in 1966 and such reports not in Medline but
      retrievable by successive reference and various alternate sources. Retrospective
      review of charts of all cases of TH at the University of Florida from 1980-1987.
      Of 135 cases so retrieved, 24 were found who had received this treatment protocol
      properly. (Ethical, moral and liability aspects prohibited a formal comparative
      study of a no medical treatment control group since this is unconscionable and
      abusive at the present state of knowledge.) RESULTS: The historical review
      revealed that there is general ignorance of the salutary effect of both topical
      and systemic steroids in reducing the rebleed rate in TH. This is so marked that
      at least five experiments reported in the literature are invalidated to a
      variable degree because all patients, in both the experimental and control
      groups, had received topical steroids. Further, that the remarkable reduction in
      the rebleed rates for control groups of theoretically medically untreated TH,
      from the vicinity of 25% or more to the vicinity of 10-15% appears to be due
      primarily, if not solely, to this now ubiquitous administration of topical
      steroids in TH. In addition, in retrospect, there are also a remarkable number
      (at least 5) of major statistical errors in this literature and another 6 studies
      of outpatients in which compliance with therapy as outpatients is not even
      considered. Therefore at least 16 (57%) of the 28 papers reviewed have serious
      flaws and doubtful or uncertain results or conclusions. Of the 9 papers which
      lead one to wrongful conclusions, 5 are prejudicial against systemic steroid
      treatment (and 2 against systemic ACA treatment, and 2 against systemic TXA
      treatment). All but one of the nine are, as a corollary, prejudicial in favor of
      non medical treatment of TH. In our 24 cases studied, none suffered a rebleeding
      episode. CONCLUSIONS: The "continuing controversy" about medical treatment of TH
      is the direct result of poor science and poor scientific methods in clinical
      trials. Because no method has yet been devised to determine which traumatic
      hyphemas will rebleed, but preventing rebleeding is about all that we can do
      maximize the outcome, we recommend that all patients with TH receive the Yasuna
      systemic steroids no touch and/or PLUS protocol in addition to current
      conventional treatment (bed rest, hospitalization for all patients under 18 years
      of age)

PMID- 10893464
TI  - Policy on conflict of interest

PMID- 10893463
TI  - From case reports to conflicts of interest.

PMID- 10893465
TI  - Quality evaluation of orthodontic information on the World Wide Web.
AB  - The phenomenal growth of the Internet has occurred because of the creation of the
      World Wide Web. The Web stores a huge amount of all sorts of health care
      information. It poses unlimited opportunities for people to access information.
      However, there is no central control and no regulatory policy regarding
      publication on the Web. The purpose of this study is to develop and apply
      published standards to perform a quality evaluation of orthodontic Web sites.
      Three hundred Web documents were visited and evaluated. The results indicate a
      variance of orthodontic information. The more professionally oriented information
      met more definitive standard criteria; on the contrary, the information designed
      for the general public met fewer standards.

PMID- 10893466
TI  - Orthodontic dental visits during 1987 and 1996.
AB  - Americans underwent approximately 355 million dental procedures during 1987,
      approximately 8% for orthodontic treatment. Individual rates of utilization vary
      and are not uniform across the population. This article provides estimates of
      orthodontic utilization for each of several socioeconomic and demographic
      categories, using household data from the 1987 National Medical Expenditure
      Survey (NMES) and the 1996 Medical Expenditure Panel Survey (MEPS). These data
      show that slightly more than 3% of the population, or approximately 39 million
      Americans, visited a dentist to receive orthodontic care nationwide during 1987
      and 1996. For those with an orthodontic visit, the mean number of visits per
      patient decreased in number from 1987 to 1996.

PMID- 10893468
TI  - Changing times

PMID- 10893467
TI  - Orthodontics and the population with special needs.
AB  - During the past 30 years, more than three quarters of individuals with mental
      retardation/developmental disabilities have been deinstitutionalized and now
      reside in our communities, relying on community physicians and dentists (even
      orthodontists) for needed services. A presentation is made to increase
      orthodontic practitioner awareness of the magnitude and dimension of the
      increasing numbers of youngsters and adults with special needs who now reside in
      their communities and require their services, and to provide some insight and
      response for the query, "Why orthodontics?"

PMID- 10893469
TI  - Defining characteristics of financially successful orthodontists.
AB  - Financially successful personality profiles in most of the business world have
      been reported to be the choleric (powerful) and the melancholy (perfect) types.
      In 1996, Hughes proposed that the same relationship possibly exists in the
      profession of orthodontics. The purpose of this study was to explore whether a
      dominant personality profile exists for the most financially successful
      orthodontists. A questionnaire was used to gather information regarding the
      financial sophistication and the dominant personality profile of each
      participating orthodontist. One hundred twenty-six of the 300 surveys distributed
      to orthodontists were returned for a response rate of 42%. For every question,
      the null hypothesis of independence was tested with the chi-square test. The null
      hypothesis of independence was rejected for a P value of less than.05. The
      results revealed that no correlation exists between the financial sophistication
      of orthodontists and their personality profiles. However, over two thirds of the
      orthodontists had the choleric (powerful) and the melancholy (perfect) as
      dominant personality types. Interestingly, the questionnaire shed much light on
      factors that do contribute to financial success in orthodontics. Although
      statistical differences are lacking in these data, certain traits about
      successful practitioners could be identified. These orthodontists (1) allow their
      practices to grow if it will increase the net income, (2) view control of
      overhead as a key principle, (3) emphasize the competence of staff in determining
      the success of practice, and (4) believe in marketing. Implementation of these
      simple and common sense principles in some orthodontic practices might affect the
      business significantly.

PMID- 10893470
TI  - Posttreatment changes after successful correction of Class II malocclusions with
      the twin block appliance.
AB  - This investigation is a continuation of a previously published study assessing
      the treatment effects of the Twin Block appliance. All active treatment was
      carried out during the mixed dentition stage (mean starting age, 9 years 1 month)
      with final follow-up for the treatment group occurring in the permanent dentition
      (mean age, 13 years 1 month). Of the original group consisting of 28
      consecutively treated severe skeletal Class II patients, 26 were available for
      follow-up. A comparison group of 28 untreated Class II subjects matched for age,
      sex, and vertical facial type was obtained from the Burlington Growth Centre
      according to the original study design. Of these 28 control subjects, 24 had 4
      year follow-up cephalometric films available. The mean age of the controls was 12
      years 11 months at the time of follow-up. During the active treatment phase, the
      Twin Block group experienced an average increase in mandibular unit length of 6.5
      mm over a mean of 14 months (annualized rate of change of 5.6 mm per year). In
      comparison, the control group experienced a 2.3 mm increase in mandibular unit
      length during the 13-month observation period (annualized rate of 2.1 mm per
      year). In the posttreatment phase, the change in mandibular unit length for the
      Twin Block group was 6.0 mm over a 36-month period (annualized rate of change of
      2.0 mm per year). The control group experienced an average increase in mandibular
      unit length of 6.7 mm over the posttreatment assessment period that was 34 months
      in duration (annualized rate of change of 2.4 mm per year). Although there was a
      slight reduction in mandibular growth rate after treatment, much of the
      significant increase in mandibular length achieved during the active phase of
      treatment with the Twin Block appliance was still present 3 years later when the
      subjects had matured into the permanent dentition stage.

PMID- 10893471
TI  - Relapse in Angle Class II Division 1 Malocclusion treated by tandem mechanics
      without extraction of permanent teeth: A retrospective analysis.
AB  - Ideal orthodontic treatment should achieve long-term stability of the occlusion.
      The mandibular incisor segment has been described as the segment that is most
      likely to exhibit relapse after treatment and retention. Therefore, relapse of
      this is a challenge that clinicians need to address. The purpose of this study is
      to evaluate the amount of relapse that may occur in Angle Class II Division 1
      patients, treated orthodontically with tandem mechanics. All cases in this study
      were treated without extraction of permanent teeth, and the patients were
      followed for at least 2 years after the end of the retention phase of treatment.
      Six predictors were investigated at pretreatment, posttreatment, and
      postretention periods. A synopsis of this study shows the correction of lower
      incisor crowding as measured by the irregularity index was stable over 5.2 years
      of postretention follow-up; but longer follow-up time revealed increased relapse
      of incisor irregularity. Intermolar width increased during treatment and remained
      stable in the follow-up period. Overjet and overbite corrections and changes in
      the lower incisor to mandibular plane angle were also stable in the follow-up
      period. In addition, the amounts of overjet correction and loss of expansion of
      intercanine distance after treatment were associated with increased irregularity
      index in the follow-up period. It appears the discrepancies between this and
      previously published works are sufficiently dramatic that the whole question of
      treatment philosophy and long-term stability may need to be reevaluated.

PMID- 10893472
TI  - Stability of anterior openbite correction with multiloop edgewise archwire
      therapy: A cephalometric follow-up study.
AB  - Successful treatment of anterior openbite malocclusion is considered one of the
      most challenging areas in orthodontics. This study was designed to evaluate the
      treatment effects of the multiloop edgewise archwire therapy in openbite
      correction and to investigate the stability of correction during a 2-year follow
      up period. The subjects consisted of 55 white patients who presented with
      anterior openbite. The subjects were divided into 2 groups: the growing group
      included 29 patients and the nongrowing group included 26 patients. The lateral
      cephalograms were analyzed for skeletal, esthetic, and dentoalveolar changes.
      Analysis of the pretreatment and posttreatment cephalometric radiographs revealed
      that the overbite increased an average of 4 mm in both the growing and the
      nongrowing groups. Analysis of the posttreatment and follow-up cephalometric
      radiographs proved that the treatment results obtained by this therapy were very
      stable. The changes in overbite during the 2-year follow-up period were not
      significant.

PMID- 10893473
TI  - Effective treatment plan for maxillary protraction: is the bone age useful to
      determine the treatment plan?
AB  - A major skeletal effect of reverse-pull headgear is a forward movement of
      maxilla, via remodeling of the circummaxillary sutures. We hypothesized that an
      evaluation of bone age would help to determine the effective planning and optimum
      timing using reverse-pull headgear. Differences in the cephalometric measurements
      between the initiation of treatment and after 1 year of treatment were calculated
      from 60 Japanese patients in mixed dentition with skeletal Class III
      malocclusions. Bone age was appraised by the Tanner-Whitehouse 2 method using
      hand-wrist radiographs at the initiation of treatment. The control groups (mean
      chronologic age, male 10.3 years and female 9.6 years) were treated by lingual
      arch and/or chincup, and the reverse-pull headgear groups (mean chronologic age,
      male 9.7 years and female 9.4 years) by reverse-pull headgear. The forward
      movement of the maxilla and increase in the palatal length were larger in the
      bone age-based younger male reverse-pull headgear subgroup than in the bone age
      based older male reverse-pull headgear subgroup. The increase of SNA in the male
      reverse-pull headgear group was significantly larger than that of the female
      reverse-pull headgear group, which had a more mature skeletal status than the
      former. In the male reverse-pull headgear group, the forward movement of the
      maxilla and increase in the palatal length showed significant inverse correlation
      with the bone age, but not with the chronologic age. These results support our
      hypothesis that the bone age is a useful clinical indicator to determine the
      effective treatment plan with reverse-pull headgear.

PMID- 10893474
TI  - Masticatory muscle activity in children and adults with different facial types.
AB  - The purpose of this study was to examine the relationship between the duration of
      masticatory muscle activity during daytime and vertical craniofacial morphology
      in children and adults. Thirty children (12 boys and 18 girls) and 30 adults (20
      men and 10 women) with normal anteroposterior skeletal relations, acceptable
      occlusions, and without any temporomandibular joint disorders, were selected as
      subjects. Activities of the masseter, temporal, and digastric muscles were
      recorded for 3 hours during daytime, excluding the periods for meals, sleep, and
      hard-exercise, using a portable electromyogram recording system. A lateral
      cephalogram was taken of each subject at the intercuspal position to divide the
      subjects into 3 different facial types, ie, low, average, and high angle groups.
      Masseter, temporal, and digastric muscle activities mainly consisted of low
      amplitude bursts during daytime. Children exhibited longer duration of temporal
      muscle activity, whereas the masseter muscle presented longer duration of
      activity in adults. The activities of masseter and digastric muscles were
      significantly related with the vertical facial type in both children and adults,
      although temporal muscle activity presented no significant relationship with the
      craniofacial morphology. The duration of masticatory muscle activity during
      daytime showed a significant difference between children and adults, indicating a
      close association with vertical craniofacial morphology in children and adults.

PMID- 10893475
TI  - Nasal impairment in prepubertal children.
AB  - The aim of this study was to examine changes in nasal resistance longitudinally
      from age 9 to 13. The study population consisted of 82 children whose nasal
      resistance was measured annually. The results showed that as nasal resistance
      significantly decreased with age, it also increased transiently at some point
      between ages 9 and 13. The timing of the transient change in resistance varied
      among individuals, but it usually occurred before age 12. No gender differences
      were observed. The results suggest that clinical signs of nasal impairment may
      periodically occur and then disappear in prepubertal orthodontic patients.

PMID- 10893476
TI  - Effect of methotrexate on the temporomandibular joint and facial morphology in
      juvenile rheumatoid arthritis patients.
AB  - Juvenile rheumatoid arthritis is a disease characterized by chronic inflammation
      in one or more joints; it affects children and adolescents up to 18 years of age.
      This disease may cause significant skeletal joint destruction, and the
      temporomandibular joint, like other joints, may become severely affected
      resulting in aberrant mandibular growth, abnormal dentofacial development, and/or
      altered orofacial muscle function. Methotrexate is the most common remittive
      agent used in juvenile rheumatoid arthritis to modify the course of inflammatory
      destruction of peripheral joints. The purpose of this study was: (1) to evaluate
      the effect of methotrexate therapy on the prevalence of temporomandibular joint
      lesions and aberration in craniofacial development in children afflicted with
      juvenile rheumatoid arthritis; (2) to further examine the relationship between
      the temporomandibular joint/cephalometric findings and rheumatologic data (ie,
      age at onset, duration of disease); and (3) to evaluate further pauciarticular-
      and polyarticular-onset disease in juvenile rheumatoid arthritis and the
      prevalence of temporomandibular joint lesions and facial dysmorphology. The
      following information was obtained from 45 patients with juvenile rheumatoid
      arthritis: (1) routine rheumatologic clinical examination data; (2) anamnestic
      temporomandibular joint evaluation data; (3) clinical temporomandibular joint
      examination data; (4) lateral cephalometric measurement data; (5) posteroanterior
      cephalometric measurement data; and (6) individually corrected axial tomographic
      data. The results demonstrated the following: (1) radiographic evidence of
      condylar degeneration was apparent in 63% of all patients with juvenile
      rheumatoid arthritis with pauciarticular patients showing less temporomandibular
      involvement than polyarticular patients; (2) polyarticular juvenile rheumatoid
      arthritis patients receiving methotrexate showed less severe temporomandibular
      joint involvement than the polyarticular patients not receiving methotrexate; (3)
      the craniofacial structure was affected to a greater extent in the polyarticular
      form of the disease; (4) the craniomandibular index scores were significantly
      greater in the polyarticular group; (5) vertical height asymmetry and chin
      deviation were noted in more than 50% of the patients; and (6) there was a
      correlation between the severity of condylar lesions and cephalometric findings
      (ie, mandibular retroposition, posterior rotation, smaller ramus and mandibular
      dimensions) and the onset and duration of the disease. In conclusion, under the
      conditions of this study, methotrexate therapy was effective in minimizing
      temporomandibular joint destruction and craniofacial dysmorphology in juvenile
      rheumatoid arthritis patients with the polyarticular form of the disease.

PMID- 10893477
TI  - Soft tissue cephalometric norms in Japanese adults.
AB  - Lateral soft tissue cephalometric standards of Japanese normal adults were
      developed with the use of Ricketts, Epker, Holdaway, and Legan cephalometric
      analyses. Cephalometric radiographs of 211 Japanese normal adults were analyzed,
      and the soft tissue measurements were compared with those of an esthetically
      pleasant Japanese subgroup and white adult sample. Statistically significant
      differences were found in the Japanese sample when compared with the white norms.
      On the other hand, the soft tissue mean values of the Japanese supernormal group
      were similar to the white norms, with the exception of the nasolabial angle and
      the lip prominence. Soft tissue cephalometric norms are specific for ethnic
      groups, but these values should not be interpreted as treatment goals. Normative
      data represent an aid for the diagnosis and planning of orthodontic treatment and
      orthognathic surgery.

PMID- 10893478
TI  - Biological derivation of a range of cephalometric norms for children of African
      American descent (after Steiner).
AB  - The purpose of this study was to report a normal range of anteroposterior apical
      base differences and concomitant interincisor inclinations and locations derived
      from a sample of American children (12 to 16 years) of African descent with
      normal occlusion (statistically defined). Standard cephalometric radiographs of
      40 boys and 40 girls were traced and the Steiner Analysis performed. In addition
      to the ANB angle, 6 supplemental anteroposterior apical base separation
      estimators were measured, mean values established, and correlation (r)
      associations performed. The range of anteroposterior apical base difference was 
      0.5 degrees to 9.5 degrees estimated by the ANB angle or a linear distance of +/
      6.5 mm using the Wits Appraisal. The angular and linear distance of the upper
      incisor to NA line (compensations) ranged from a low of 12 degrees and 3 mm to a
      high of 39 degrees and 14 mm. The angular and linear distance of the lower
      incisor to the NB line ranged from a low of 17 degrees and 3 mm to a high of 47.5
      degrees and 17.5 mm. Biologically, the results suggested a wide range of equally
      acceptable sagittal apical base relationships and associated compensations in
      upper and lower incisor inclinations; normal occlusion was viewed as the
      reference point. Considering the usage of such descriptive terms as "ideal,"
      "acceptable compromises," and "individualized treatment goals," to describe the
      angulation and inclination of the incisor teeth, the need for a distinction
      between biologically derived reference norms and esthetic preference reference
      norms is apparent when analyzing normal occlusion.

PMID- 10893479
TI  - Tying twin brackets.
AB  - To achieve orthodontic tooth movement, archwires must be tied to the bracket
      slots. Metal or elastic ligatures are used for this purpose, and the way they are
      tied affects tooth movement. Because of their design, twin brackets can be tied
      in a large variety of ways. Knowing how to use all the bracket's resources makes
      for better and faster treatment results.

PMID- 10893480
TI  - Treatment of a Class I malocclusion with a carious mandibular incisor and no
      Bolton discrepancy.
AB  - Occasionally orthodontists must plan treatment for a patient with extensive
      caries or a traumatic injury to one mandibular incisor. If the patient has a
      Bolton discrepancy, one treatment option could involve extraction of the affected
      mandibular incisor. However, if the patient does not have a Bolton discrepancy
      and a mandibular incisor is extracted, the treatment becomes more complicated.
      This case report will present and discuss the ramifications of extracting one
      mandibular incisor in a patient without an anterior tooth-size discrepancy. The
      CDABO Student Case Selection Committee chose this case for publication.

PMID- 10893482
TI  - J. Edward gilda, DDS, MS

PMID- 10893481
TI  - Powering up your PowerPoint presentations.

PMID- 10893483
TI  - Genetic association study between alpha 1-antichymotrypsin polymorphism and
      Alzheimer disease in Chinese Han population.
AB  - We investigated a common signal peptide polymorphism in the alpha 1
      antichymotrypsin (ACT) gene in 125 sporadic Alzheimer disease (AD) patients and
      141 healthy control subjects in Chinese Han population. We found no significant
      difference in the distribution of ACT polymorphism between AD cases and controls,
      and failed to detect any effects of ACT genotypes associated with AD. Thus, our
      data do not support the involvement of ACT polymorphism in the risk of AD in
      Chinese Han population. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:133-135,
      2000.

PMID- 10893484
TI  - A European multicenter association study of HTR2A receptor polymorphism in
      bipolar affective disorder.
AB  - The available data on the role of 5-HT in a variety of behaviors support the
      hypothesis that a dysfunction in brain serotoninergic system activity contributes
      to vulnerability to major depression. The diversity in the electrophysiological
      actions of 5-HT in the central nervous system can now be categorized according to
      receptor subtypes and their respective effector mechanisms. In particular, the
      implication of central postsynaptic 5-HT2A receptor in affective disorders has
      been supported by findings consistent with the hypothesis of 5-HT2A receptor up
      regulation in depression. For these reasons, the 5-HT2A receptor (HTR2A) gene can
      be considered as a candidate gene in bipolar affective disorder (BPAD). We tested
      the possible genetic contribution of the polymorphic DNA variation T102C in exon
      1 of HTR2A (chromosome 13q14-21) gene in a large European multicentric case
      control sample. Allele and genotype frequencies, as well as homo-heterozygote
      distributions were compared between the two groups of 309 bipolar affective
      disorder patients and 309 matched controls. No significant differences were
      observed in the allelic and genotypic (also for homo-heterozygote) distribution
      between BPAD and controls. These results indicate that, in our sample, the 5-HT2A
      receptor polymorphism studied is unlikely to play a major role in the genetic
      susceptibility to BPAD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:136-140,
      2000.

PMID- 10893485
TI  - Novel polymorphisms of the human cholecystokinin A receptor gene: an association
      analysis with schizophrenia.
AB  - The cholecystokinin A receptor (CCK-AR) modulates CCK-stimulated dopamine release
      in the posterior nucleus accumbens, and its gene is mapped to 4p15.2-15.1 with
      the dopamine receptor 5 (DR5) gene. We speculated that alterations in the CCK-AR
      lead to an increase in dopamine release, which may in turn constitute a
      predisposition in schizophrenia. We investigated genetic variations in the
      promoter region and the coding region of the CCK-AR gene. An association analysis
      was conducted between 83 unrelated schizophrenic patients and 80 healthy
      controls. Novel polymorphisms (201A-->G, 246G-->A in the promoter region, 1260T-
      >A, 1266T-->C in intron 1 within the 3' mRNA splice acceptor site consensus
      sequence, and Leu306Leu in exon 5) were found in addition to the variants (608G-
      >A in intron 1, 3849C-->T [Ile296Ile] in exon 5) reported previously. Significant
      differences were found in the allele frequencies of the 201A-->G nucleotide
      substitution in the promoter region between patients and controls (P = 0.0181,
      odds ratio: 1.972, after Bonferroni correction: P = 0.0543). These differences
      were also found between the patients with paranoid type and controls (P = 0.0274,
      odds ratio = 3.667, after Bonferroni correction: P = 0.0822). Our analyses
      suggest that the 201A allele frequency was higher in the schizophrenic group,
      especially in the paranoid type, than in the control group at a rate that was not
      quite significant after Bonferroni correction. Am J. Med Genet. (Neuropsychiatr.
      Genet.) 96:141-145, 2000.

PMID- 10893486
TI  - Familial association between allergic disorders and depression in adult Finnish
      twins.
AB  - Clinical studies have shown a relationship between allergic disorders and
      depression, panic disorder, attention deficit/hyperactivity disorder, and social
      anxiety for a significant subset of patients with these disorders. The nature of
      the relationship, whether due to shared environmental or biologic vulnerabilities
      or as a result of the stress of chronic illness, has been less clear. By
      examining the covariance of atopic disorders and depressive symptoms in a
      community sample of monozygotic (MZ) and dizygotic (DZ) twins, the contribution
      of genetic and/or shared environmental etiological factors can be established. A
      Finnish sample of 1337 MZ and 2506 DZ twin pairs, ages 33-60 years, was sent
      questionnaires inquiring about history of asthma, eczema, and atopic rhinitis, as
      well as the Beck Depression Inventory (BDI). The nature of the covariation
      between twins of these symptoms was investigated by fitting competing genetic and
      environmental models. Within-person correlation between atopic symptoms and BDI
      was 0.103 (P < 0.001) for the total sample. Using the Mx statistical modeling
      program to fit the data to competing quantitative genetic models, the best
      fitting model estimated that 64% of the association between atopy and BDI was due
      to shared familial vulnerability, primarily additive genetic influences. Although
      the measures for allergic disorders and depression are crude, this study supports
      the hypothesis that there is a small shared genetic risk for atopic and
      depressive symptoms, and if replicated, may open research for common mechanisms
      between allergic and depressive disorders. Am. J. Med. Genet. (Neuropsychiatr.
      Genet.) 96:146-153, 2000.

PMID- 10893487
TI  - Bipolar disorder and variation at a common polymorphism (A1832G) within exon 8 of
      the Wolfram gene.
AB  - A number of linkage studies provide evidence consistent with the existence of a
      bipolar susceptibility gene on chromosome 4p16. The gene for Wolfram syndrome, a
      rare recessive neurodegenerative disorder, lies in this region and has recently
      been cloned. Psychiatric disturbances including psychosis, mood disorder, and
      suicide have been reported at increased frequency in Wolfram patients and in
      heterozygous carriers of a Wolfram mutation. In the current investigation we have
      undertaken a case-control association study using a single nucleotide
      polymorphism (causing an amino acid change) in exon 8 of the Wolfram gene in a UK
      Caucasian sample of 312 Diagnostic and Statistical Manual of Mental Disorders
      (fourth edition; DSM IV) bipolar I probands and 301 comparison individuals. We
      found no evidence that variation at this polymorphism influences susceptibility
      to bipolar disorder. It remains possible that variation at other sites within or
      near the Wolfram gene plays important roles in determining susceptibility to
      affective illness. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:154-157, 2000.

PMID- 10893488
TI  - Mutational analysis of the Wolfram syndrome gene in two families with chromosome
      4p-linked bipolar affective disorder.
AB  - Bipolar affective disorder (BPAD) is a complex disease with a significant genetic
      component. Heterozygous carriers of Wolfram syndrome (WFS) are at increased risk
      of psychiatric illness. A gene for WFS (WFS1) has recently been cloned and mapped
      to chromosome 4p, in the general region we previously reported as showing linkage
      to BPAD. Here we present sequence analysis of the WFS1 coding sequence in five
      affected individuals from two chromosome 4p-linked families. This resulted in the
      identification of six polymorphisms, two of which are predicted to change the
      amino acid sequence of the WFS1 protein, however none of the changes segregated
      with disease status. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:158-160,
      2000.

PMID- 10893489
TI  - Serotonin-2C and serotonin-1A receptor genes are not associated with psychotic
      symptomatology of mood disorders.
AB  - The serotonergic system is involved in both pathophysiology and treatment of mood
      disorders. In the present study we investigated the possible influence of the
      polymorphisms of the serotonin-1A and 2C receptor genes on the symptomatology of
      mood disorders. Eighty-four inpatients affected by mood disorders (72 bipolar and
      12 major depressive disorder) were assessed by the Operational Criteria Checklist
      for Psychotic Illness to score their lifetime psychotic symptomatology. The
      subjects were also typed for 5HT1A and 5HT2C variants using polymerase chain
      reaction techniques. No association was found between 5HT2C and psychopathology
      as defined by the four symptomatologic factors used as phenotype definition
      (mania, depression, delusion, and disorganization) even when bipolar subjects
      were analyzed separately. Only one subject with the 5HT1A variant was observed.
      Genetic variation at the 5HT1A and 5HT2C receptor genes does not, therefore, play
      a major role in the pathogenesis of mood disorders symptomatology. Am. J. Med.
      Genet. (Neuropsychiatr. Genet.) 96:161-166, 2000.

PMID- 10893490
TI  - No association between butyrylcholinesterase K-variant and Alzheimer disease in
      Chinese.
AB  - Increased butyrylcholinesterase (BChE) activity has been reported to be
      associated with the formation of amyloid plaques and neurofibrillary tangles and
      may consequently be involved in the pathogenesis of Alzheimer disease (AD).
      Because the catalytic activity of BChE-K variant is reduced by one-third compared
      with non-variant, we speculated that BChE-K variant has a protective effect on
      AD. However, Lehmann et al. [1997] reported a synergistic effect between the
      genes for BChE-K variant and apolipoprotein E (ApoE) epsilon 4, which increases
      the risk for late onset AD. In the present study, we tested 89 Chinese AD
      patients and 101 Chinese controls and found no evidence of association between
      BCHE-K and AD of either early or late onset (age > 65 years). No evidence of a
      synergistic effect was found between the BCHE-K variant and APOE epsilon 4 in
      this study. Our data suggest that BChE-K variant has no modifying effect on the
      pathogenesis of AD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:167-169, 2000.

PMID- 10893491
TI  - Association analysis of 5HT transporter gene in bipolar disorder in the Indian
      population.
AB  - A variable number tandem repeat (VNTR) polymorphism consisting of multiple copies
      of a 17-bp repeat in the second intron of the serotonin transporter gene (SERT)
      has been reported. Different alleles of this VNTR have been found to be
      associated with bipolar disorder and schizophrenia. These findings have been
      confirmed in some populations, but disconfirmed in others. Furthermore,
      significant ethnic variations in the distribution of these alleles both in normal
      and patient populations also have been reported. We analyzed the VNTR
      polymorphism in 50 Indian patients with bipolar disorder and in ethnically
      matched controls. Two alleles corresponding to 10 and 12 repeats of the VNTR were
      found in both groups. There were no significant differences either in allele
      frequency or genotype frequency between the two groups. The nine-repeat allele
      that has been reported in Japanese and Caucasian populations was absent in our
      sample. Although it will be important to extend the present study in a larger
      sample, our initial results do not suggest any large association with alleles of
      the VNTR in the SERT gene and bipolar disorder in Indian patients. Am. J. Med.
      Genet. (Neuropsychiatr. Genet.) 96:170-172, 2000.

PMID- 10893492
TI  - Schizophrenia and smoking: evidence for a common neurobiological basis?
AB  - Several previous investigations have suggested that the gene for the alpha 7
      nicotinic receptor may play a role in the pathogenesis of schizophrenia and may
      be responsible for the heavy smoking among schizophrenic patients. In a study of
      129 healthy controls and 127 schizophrenic, schizoaffective, and bipolar patients
      we have aimed 1) to confirm the potential association between schizophrenia and
      the alpha 7-nicotinic receptor, 2) to test the diagnostic specificity of alpha 7
      receptor subunits with respect to psychiatric diagnoses, and 3) to investigate
      potential receptor differences between smokers and nonsmokers in the general
      population. Our analysis included the two dinucleotide polymorphisms D15S1360 and
      L76630 that are localized in a genomic fragment containing the alpha 7-nicotinic
      receptor gene CHRNA7. Highly significant differences (P < 0.0001) between the
      allele distributions of patients and controls were detected for these two markers
      with all three diagnostic subgroups contributing to the discrimination. An
      independently ascertained replication sample of 24 patients confirmed this
      finding. Our results suggested an unspecific vulnerability that depended on the
      severity of overall psychopathology in terms of the co-occurrence of
      psychopathology with no clear-cut boundary between the diagnostic entities. In
      comparison with healthy controls, this vulnerability was lowest among
      schizophrenics, intermediate among bipolars, and highest among schizoaffectives.
      As to the question of alpha 7-receptor differences between smokers and nonsmokers
      among the healthy control subjects, our analysis revealed no significant
      differences, thus indicating that the differences between patients and controls
      are more than just a smoker/nonsmoker distinction. Am. J. Med. Genet.
      (Neuropsychiatr. Genet.) 96:173-177, 2000.

PMID- 10893493
TI  - Association and linkage studies of CRH and PENK genes in bipolar disorder: a
      collaborative IGSLI study.
AB  - Corticotropin-releasing hormone (CRH) and proenkephalin (PENK) are hypothalamic
      peptides involved in the stress response and hypothalamic-pituitary axis
      regulation. Previous research has implicated these peptides in the pathogenesis
      of affective disorders. In this study we investigated two polymorphisms located
      in the genes that code for CRH and PENK by means of association and linkage
      analyses. A total of 138 bipolar patients and 108 controls were included in the
      association study. In addition, 24 families were available for linkage analysis,
      including six families of probands with documented periodic positivity of
      dexamethasone suppression tests (DST) during remission. We found no association
      of bipolar disorder with either gene. Similarly, we did not find any evidence of
      linkage (P = 0.56 for CRH and 0.52 for PENK) in the entire sample or in the
      subsample of families of DST positive probands. In conclusion, our study does not
      support the hypothesis that genes coding for CRH or PENK contribute to the
      genetic susceptibility to bipolar disorder. Am. J. Med. Genet. (Neuropsychiatr.
      Genet.) 96:178-181, 2000.

PMID- 10893494
TI  - Association of bipolar disorder with the 5178 polymorphism in mitochondrial DNA.
AB  - Parent-of-origin effect in transmission of bipolar disorder and abnormal
      phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) findings in the brain
      in patients with bipolar disorder implicate pathophysiological role of
      mitochondrial DNA in bipolar disorder. The authors examined possible association
      of bipolar disorder with the 5178 polymorphism in mitochondrial DNA. Genotype
      frequencies of the 5178 polymorphism were examined by polymerase chain reaction
      restriction fragment length polymorphism method in 145 patients with bipolar
      disorder and 184 controls. The rate of 5178C genotype was significantly higher in
      patients with bipolar disorder (81/125 (64.8%), P < 0.05) compared with controls
      (98/184 (53.2%)) when paternally transmitted cases were excluded. This effect was
      more prominent in patients with bipolar II disorder (5178C: 28/37, 75.6%, P <
      0.02 to controls). Bipolar II patients with 5178A genotype without family history
      had significantly later age at onset (56.0 +/- 14.7 years, P < 0.05) than other
      bipolar patients. Brain intracellular pH measured by (31)P-MRS was significantly
      higher in bipolar patients with 5178A (7.04 +/- 0.03, n = 7, P < 0.05) than those
      with 5178C (7.00 +/- 0.03, n = 7). There was no difference of subcortical
      hyperintensity scores by magnetic resonance imaging between patients with 5178A
      and those with 5178C. These results suggest that the 5178 polymorphism in
      mitochondrial DNA may regulate vulnerability to bipolar disorder via alteration
      of brain energy metabolism. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:182
      186, 2000.

PMID- 10893495
TI  - Association of dopamine D3-receptor gene variants with neuroleptic induced
      akathisia in schizophrenic patients: a generalization of Steen's study on DRD3
      and tardive dyskinesia.
AB  - Neuroleptic induced akathisia is a common and distressful extrapyramidal side
      effect of antipsychotic treatment. A significant proportion of the variability of
      its development has been left unexplained and has to be attributed to individual
      susceptibility. Since hereditary factors have been discussed in the etiology of
      acute akathisia (AA), part of the individual susceptibility might be of genetic
      origin. Moreover, AA is regarded as a forerunner of tardive dyskinesia, a drug
      induced chronic movement disorder, which may be associated with homozygosity for
      the Ser9Gly variant of the DRD3 gene. Considering expression studies, which
      demonstrated functional variants of DRD3 polymorphisms, we investigated whether
      homozygosity for the Ser9Gly variant of the DRD3 gene is associated with AA.
      Homozygosity for the Ser9Gly variant of the DRD3 gene was connected to an 88%
      incidence of AA as compared with a considerably lower 46.9% incidence of AA in
      schizophrenic patients nonhomozygous for the 2-2 allele (exact P = 0.0223). Am.
      J. Med. Genet. (Neuropsychiatr. Genet.) 96:187-191, 2000.

PMID- 10893496
TI  - High cognitive outcome in an adolescent with mut- methylmalonic acidemia.
AB  - Methylmalonic acidemia is an inborn error of metabolism known to be a cause of
      ketoacidosis and mental retardation. The less severe mut(-) form of the disorder,
      however, has been described with only mild to moderate cognitive deficits or,
      rarely, with normal neurodevelopment in asymptomatic cases. Nevertheless, there
      has been no detailed documentation of long-term neuropsychological function in
      the mut(-) form and relatively few IQ scores. We performed longitudinal
      developmental and neuropsychological assessments on a girl with symptomatic mut(
      ) methylmalonic acidemia whose biochemical abnormalities were in the moderately
      severe range and who had had recurrent episodes of ketoacidosis. At almost 12
      years of age, her full scale IQ on the Wechsler Intelligence Scale, third
      edition, was 129 with very superior and superior scores on nonverbal and verbal
      skills, respectively. On the National Achievement Test she scored above the 99th
      percentile in the Basic Battery and is considered to be a gifted student. This
      outcome suggests that the spectrum of cognitive attainment in mut(-)
      methylmalonic acidemia is wide and that even a moderate degree of biochemical
      severity with ketoacidotic episodes may not result in cognitive deficit. Am. J.
      Med. Genet. (Neuropsychiatr. Genet.) 96:192-195, 2000.

PMID- 10893497
TI  - Haplotype transmission disequilibrium and evidence for linkage of the CHRNA7 gene
      region to schizophrenia in Southern African Bantu families.
AB  - Recent reports have strongly linked markers near the alpha-7 nicotinic
      cholinergic receptor subunit gene on human chromosome 15q13-q14 to a sensory
      gating deficit common in schizophrenics, and have shown positive though non
      significant results linking this region to the primary phenotype of schizophrenia
      in a sample of North American families. We therefore tested for linkage between
      markers in this region of chromosome 15q and schizophrenia in a sample of 15
      multiply affected and 5 single case families with schizophrenia drawn from the
      Bantu-speaking black population of South Africa. An initial replication using
      markers from the original study gave an affected-only LOD score maximum of 1.08
      under a recessive model at Theta=0.00 for D15S1360, a dinucleotide polymorphism
      found on the same YAC as the alpha-7 receptor gene. Nonparametric affected-only
      multipoint analysis gave a Z-score of 1. 29, P=0.098, for D15S1360, and Z=1.45,
      p=0.075 for D15S118. We then increased the resolution of the map with an extended
      set of 20 markers. Again, two peaks were observed, with NPL scores of 1.81,
      p=0.037, at D15S1043 and 1.79 at D15S1360 and 1.80 at D15S1010, both p=0.037.
      Transmission disequilibrium testing of data from D15S1360 gave an allele-wise and
      genotype-wise chi(2) of 6.59, 2 df, p=0.037. Haplotype transmission
      disequilibrium testing using a restricted allele and haplotype set from D15S1043
      and D15S1360 gave a global chi(2) of 10.647, 4 df, P=0.007, and a maximum chi(2)
      of 6.567, 1 df, P=0.004 for excess transmission of the 1.2 haplotype into
      affected offspring. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:196-201, 2000.

PMID- 10893498
TI  - Association between the serotonin transporter promoter polymorphism and
      personality traits in a primarily female population sample.
AB  - The serotonin transporter (5-HTT) regulates serotonergic neurotransmission and is
      thought to influence emotion. A 5-HTT-linked polymorphic region (5-HTTLPR) has
      two common variants, short (s) and long (l). We previously found population and
      within-family associations between the lower-expressing s allele and neuroticism,
      a trait related to anxiety, hostility, and depression, on a standard measure (the
      NEO Personality Inventory, Revised [NEO-PI-R]) in a primarily male population
      (n=505), and that the s allele was dominant. We investigated this association in
      a new sample (n=397, 84% female, primarily sib-pairs). The results robustly
      replicated the 5-HTTLPR neuroticism association, and the dominance of the s
      allele. Combined data from the two studies (n=902) showed a highly significant
      association between the s allele and higher NEO Neuroticism both across
      individuals and within families. Association between genotype and a related
      measure, Anxiety on the 16PF inventory, was replicated in the new population and
      within families in the combined sample. Association to another trait, estimated
      TPQ Harm Avoidance, was not replicated in the new sample but found only within
      the combined sibship group. Another association found in our original study,
      between the s allele and lower scores on NEO-PI-R Agreeableness, was also
      replicated and was more robust in the current and the combined samples.
      Associations between the functional 5-HTTLPR polymorphism were similar in women
      and men. These results help to define specific personality features reproducibly
      associated with 5-HTTLPR genotype. Such associations were strongest for traits
      defined by the NEO, enhancing the attractiveness of the five-factor personality
      model in genetic research on complex behavioral dimensions. Am. J. Med. Genet.
      (Neuropsychiatr. Genet.) 96:202-216, 2000. Published 2000 Wiley-Liss, Inc.

PMID- 10893499
TI  - Investigation of the human serotonin 6 [5-HT6] receptor gene in bipolar affective
      disorder and schizophrenia.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that mediates a wide
      range of central nervous functions by activating multiple 5-HT receptor subtypes.
      A possible irregularity of serotonergic neurotransmission has been implicated in
      a variety of neuropsychiatric diseases. In the present study, we performed a
      systematic mutation scan of the complete coding region and splice junctions of
      the 5-HT(6) receptor gene to explore the contribution of this gene to the
      development of bipolar affective disorder and schizophrenia. Investigating 137
      unrelated individuals (including 45 bipolar affective patients, 46 schizophrenic
      patients, and 46 unrelated controls), we identified six single base substitutions
      (126G/T, 267C/T, 873+30C/T, 873+128A/C, 1128G/C, 1376T/G). Comparing frequencies
      between patients and controls, we observed a significant overrepresentation of
      the 267C allele among bipolar patients (P=0. 023 not corrected for multiple
      testing). This finding was followed up in an independent sample of 105 bipolar
      family trios using a family-based association design. Fifty-one transmissions
      could be examined. In 30 cases allele 267C and in 21 cases allele 267T were
      transmitted to the affected offspring. Although this result was far from
      statistical significance (transmission disequilibrium test=1.59, P=0.208), the
      limited number of possible transmissions may have prevented detection of smaller
      effects. Our preliminary data suggest that bipolar affective disorder may be
      associated with variation in the 5-HT(6) gene. It will be important to extend the
      present analysis to larger samples. Am. J. Med. Genet. (Neuropsychiatr. Genet.)
      96:217-221, 2000.

PMID- 10893500
TI  - Novelty seeking traits and D4 dopamine receptors.

PMID- 10893501
TI  - No support for linkage to the bipolar regions on chromosomes 4p, 18p, or 18q in
      43 schizophrenia pedigrees.

PMID- 10893502
TI  - Support for linkage of autism and specific language impairment to 7q3 from two
      chromosome rearrangements involving band 7q31.
AB  - Childhood autism is characterised by impairments in communication and reciprocal
      social interaction together with restricted/stereotyped interests, which are
      evident before 3 years of age. Specific developmental disorders of speech and
      language (SDDSL) are characterised by impairment in the development of expressive
      and/or receptive language skills which is not associated with intellectual,
      sensory, physical, or neurological impairment. Family and twin studies indicate a
      substantial genetic component in the aetiology of both disorders. They also
      reveal increased rates of SDDSL in relatives of autistic individuals, suggesting
      that this phenotype can represent one manifestation of the genetic liability for
      autism. Modelling of the recurrence risk for autism and milder phenotypes, such
      as SDDSL, suggest that three or four epistatic loci may be aetiologically
      involved. A recently published linkage study of an exceptional family with an
      apparently dominantly inherited SDDSL implicated chromosome band 7q31 as the site
      of the putative susceptibility locus (SPCH1). This region of chromosome 7 also
      shows strong linkage in multiplex families with autism. We present two
      individuals (one has autism, the other SDDSL) with different, apparently balanced
      chromosome rearrangements involving a breakpoint at 7q31.3. Fluorescence in situ
      hybridisation was used to localise the breakpoints to an approximately 1 cM
      interval between CFTR and D7S643. Our findings may be of interest and relevance
      to the genetic aetiology of autism, and helpful in the search for susceptibility
      loci for SDDSL and autism. Am. J. Med. Genet. (Neuropsychiatr. Genet. ) 96:228
      234, 2000.

PMID- 10893503
TI  - Lack of evidence for linkage to chromosomes 13 and 8 for schizophrenia and
      schizoaffective disorder.
AB  - A previous report [Blouin et al., 1998: Nat Genet 20:70-73] suggesting linkage to
      chromosomes 13q32 and 8p21 in families with schizophrenia led us to investigate
      these regions in a large set of 301 multiplex families with schizophrenia.
      Multipoint analyses failed to reveal evidence for linkage to any portion of
      chromosome 13, while only a weakly positive score was present on 8p using the
      identical marker reported in the earlier report. Failure to confirm the Blouin et
      al claims in a substantially larger cohort adds emphasis to the inconsistency of
      the findings concerning linkage in schizophrenia. Am. J. Med. Genet.
      (Neuropsychiatr. Genet.) 96:235-239, 2000.

PMID- 10893504
TI  - Lung cancer among workers in chromium chemical production.
AB  - BACKGROUND: An elevated risk of lung cancer among workers in chromate production
      facilities has previously been reported. This excess risk is believed to be the
      result of exposure to hexavalent chromium. There have been mixed reports about
      whether trivalent chromium exposure is also associated with an excess lung cancer
      risk. Previous studies of measured hexavalent chromium exposure and lung cancer
      risk have not examined cigarette smoking as a risk factor. METHODS: A cohort of
      2,357 workers first employed between 1950 and 1974 at a chromate production plant
      was identified. Vital status of the workers was followed until December 31, 1992.
      Work histories of cohort members were compiled from the beginning of employment
      through 1985, the year the plant closed. Annual average exposure estimates, based
      on historical exposure measurements, were made for each job title in the plant
      for the years 1950-1985. These exposure estimates were used to calculate the
      cumulative hexavalent chromium exposure of each member of the study population.
      Following closure of the plant, settled dust samples were collected and analyzed
      for hexavalent and trivalent chromium. The trivalent/hexavalent concentration
      ratios in each plant area were combined with historic air-sampling data to
      estimate cumulative trivalent chromium exposure for each individual in the study
      cohort. Smoking status (yes/no) as of the beginning of employment and clinical
      signs of potential chromium irritation were identified from company records.
      RESULTS: Cumulative hexavalent chromium exposure showed a strong dose-response
      relationship for lung cancer. Clinical signs of irritation, cumulative trivalent
      chromium exposure, and duration of work were not found to be associated with a
      risk of lung cancer when included in a proportional hazards model with cumulative
      hexavalent chromium exposure and smoking. Age-specific data on cumulative
      hexavalent chromium exposure, observed and expected numbers of lung cancer cases,
      and person-years of observation are provided. CONCLUSIONS: Cumulative hexavalent
      chromium exposure was associated with an increased lung cancer risk; cumulative
      trivalent chromium exposure was not. The excess risk of lung cancer associated
      with cumulative hexavalent chromium exposure was not confounded by smoking
      status. The current study offers the best quantitative evidence to date of the
      relationship between hexavalent chromium exposure and lung cancer. Am. J. Ind.
      Med. 38:115-126, 2000. Published 2000 Wiley-Liss, Inc.

PMID- 10893505
TI  - Clinical findings of irritation among chromium chemical production workers.
AB  - BACKGROUND: Several reports of workers in chromate production and chromeplating
      have indicated that exposure to hexavalent chromium is associated with skin and
      nasal irritation. METHODS: A cohort of 2, 357 workers first employed between 1950
      and 1974 at a chromate production plant was identified. Clinical findings of
      irritation were identified by a physician as a result of routine examinations or
      visits to the medical clinic by members of the cohort. Percentages of the cohort
      with various clinical findings, the time from hire to occurrence of the first
      finding, and the mean and median annual hexavalent chromium (measured as CrO(3))
      concentration for the job title where the clinical finding first occurred were
      determined. A proportional hazards model was used to evaluate the relationship
      between hexavalent chromium exposure and first occurrence of each of the clinical
      findings. RESULTS: Nasal irritation and nasal ulceration were the most common
      clinical findings reported, occurring in more than 60% of the cohort. The average
      time to first occurrence of these findings was less than 3 months, whereas the
      time to first occurrence of the other findings ranged from 10 to 22 months.
      Median exposure to hexavalent chromium at the time of occurrence for most of the
      findings was about 20 microg/m(3). The proportional hazards model indicated that
      ulcerated nasal septum, irritated skin, and perforated eardrum were significantly
      associated with ambient hexavalent chromium exposure; all clinical findings with
      the exception of conjunctivitis and irritated skin were associated with the
      calendar year of hire, with the risk being lower as the calendar year of hire
      became more recent. Annual average ambient hexavalent chromium concentrations
      generally dropped in the plant over the period of the study. CONCLUSIONS: Workers
      in the chromate production plant in this study experienced a variety of nasal and
      skin irritations. Irritated and ulcerated nasal septa, in particular, were quite
      common clinical findings, occurring in over 60% of the cohort, and they occurred
      in relatively short periods of time-less than 3 months from date of hire. Annual
      average concentrations of chromium may not be a good predictor of clinical
      findings of irritation. Am. J. Ind. Med. 38:127-131, 2000. Published 2000 Wiley
      Liss, Inc.

PMID- 10893506
TI  - Implications of different fiber measures for epidemiologic studies of man-made
      vitreous fibers.
AB  - BACKGROUND: Several researchers have proposed fiber size ranges representing
      hypotheses about the biological activity of fibers. Each of these indices has a
      biologically plausible rationale, yet they propose different fiber dimensions.
      METHODS: Four biologically based and one standard fiber analytic method index,
      the NIOSH 7400 method with B rules, were evaluated in air monitoring data
      collected in a variety of fiber glass (FG) manufacturing settings to determine
      their impact on an assessment of fiber exposure for an epidemiologic study of the
      risk of respiratory cancer among FG production workers. RESULTS: All indices
      varied considerably within and among the range of fiber size distributions
      sampled in the FG factories. CONCLUSIONS: The asymptotic relative efficiencies
      (R(2)) calculated among the five indices indicate a potentially important loss of
      power from the use of the standard method index, if one of the biologically based
      indices is more closely related to the disease outcome in an epidemiologic study.

PMID- 10893507
TI  - Nonfatal work-related inhalations: surveillance data from hospital emergency
      departments, 1995-1996.
AB  - BACKGROUND: Data from a stratified sample of hospital emergency rooms in the USA
      were used to describe nonfatal work-related inhalation injuries and illnesses
      during July 1995 to July 1996. METHODS: Information was abstracted from emergency
      room records by the Consumer Product Safety Commission (CPSC) as part of the
      National Electronic Injury Surveillance System (NEISS) for all work-related
      injuries and illnesses regardless of product involvement. RESULTS: There were an
      estimated 44,423 occupational inhalation cases nationwide, with an annual rate of
      3.6 cases/10(4) workers/year. The rate for men (4.4 cases/10(4)) was greater than
      that observed for women (2.6 cases/10(4)), and the rates tended to decline with
      increasing age. An estimated 4.6% of the cases were hospitalized for further
      treatment. The highest rate by industry was 16.4 cases/10(4) for public
      administration (which included fire and police departments). Among non
      firefighters, there were an estimated 6,470 cases nationwide in which respiratory
      symptoms or conditions were noted, which yielded an annual rate of 0.5
      cases/10(4) (95% CI 0.3, 0.7). Chlorine compounds were a common agent for the
      cases with adverse respiratory outcomes. CONCLUSIONS: The NEISS data provide an
      efficient method to learn about the national frequency of work-related inhalation
      injuries and illnesses. The National Institute for Occupational Safety and Health
      (NIOSH) is exploring two ways to use these data: first, to routinely review the
      reports to conduct surveillance for work-related inhalation cases; and second, to
      consider working with CPSC to conduct follow-back interviews of selected cases in
      order to learn more about the circumstances of the exposure, prior training of
      the case, and outcome of the exposure. Am. J. Ind. Med. 38:140-148, 2000.
      Published 2000 Wiley-Liss, Inc.

PMID- 10893508
TI  - Occupational sunlight exposure in relation to suicide among electric utility
      workers.
AB  - BACKGROUND: Occupational sunlight exposure was examined in relation to death from
      suicide in a United States cohort of 138,905 male electric utility workers.
      METHODS: Case-control sampling included 536 deaths from suicide and 5,348
      eligible controls randomly selected from the cohort. Exposure was classified
      based on work history linked to indices of cumulative sunlight exposure. RESULTS:
      Mortality from suicide was not associated with estimates of recent and career
      occupational sunlight exposure, with adjusted odds ratios around unity.
      Occupational sunlight exposure was positively associated with nonviolent
      suicides, but no dose-response gradient was observed and risk estimates were
      notably imprecise. CONCLUSIONS: These data provide evidence against an
      association between occupational sunlight exposure and mortality from suicide.

PMID- 10893509
TI  - Evaluation of worker safety and health training.
AB  - BACKGROUND: Few studies of worker training have addressed the impact on
      participant's health and safety behaviors and efforts to change health and safety
      conditions at the workplace. The present study is an evaluation of these impacts
      as reported by workers and managers. METHODS: The UAB/CLEAR program has trained
      over 1,000 participants since 1992. A survey was mailed to a sample of workers
      and all participating managers. RESULTS: The results revealed that both groups
      reported increasing personal safety and health behavior, both contributed to
      emergency preparedness, and both influenced the elimination of hazardous
      chemicals. Managers reported greater influence on health and safety which may be
      explained by their relatively more powerful position. However, an impressive
      percentage of workers reported influencing changes. CONCLUSIONS: This pattern
      indicates that when the environment supports joint decision making by workers and
      management, initiating changes becomes easier.

PMID- 10893510
TI  - Occupational airway sensitizers: an overview on the respective literature.
AB  - BACKGROUND: Worldwide, there is rigorous scientific activity concerning the
      further development of work safety regulations involving airway-sensitizing
      substances. Technical directives on hazardous substances are enforced in several
      countries and are being continuously updated. The European Union has established
      a code for several occupational substances, now labeled R 42 ("may cause
      sensitization by inhalation"). METHODS: We present an overview of the literature
      dealing with allergic occupational asthma. The literature was selected according
      to criteria of study design and diagnostic test methods. Approximately 300
      publications were reviewed including both epidemiological studies and individual
      case reports. RESULTS: Airway sensitizers are systematically arranged and
      separately listed according to chemicals and their origin from animals, plants,
      and microorganisms. The clinical data as well as threshold limit values (TLV) and
      R 42 labeling of 250 airway-sensitizing substances are presented. CONCLUSIONS:
      The most common sensitizing substances causing occupational asthma were dust of
      cereal flours, enzymes, natural rubber latex, laboratory animals as well as low
      molecular substances such as isocyanates and acid anhydrides.

PMID- 10893511
TI  - Malignant pleural mesothelioma presenting as spontaneous pneumothorax: a case
      series and review.
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is thought to arise from the
      mesothelial cells that line the pleural cavities. Most patients initially
      experience the insidious onset of chest pain or shortness of breath, and it
      rarely presents as spontaneous pneumothorax. CASE REPORTS: We report four
      patients who presented in this manner. Three of the patients were exposed to
      asbestos directly or indirectly at shipyards during World War II; the fourth was
      exposed as an insulator's wife. Two of our cases were not recognized to have MPM
      on histologic examination at first thoracotomy and remained asymptomatic for 12
      and 22 months, respectively. In none of the patients described herein, was
      spontaneous pneumothorax the cause of death. CONCLUSIONS: Since many people were
      exposed to asbestos during and after World War II, spontaneous pneumothorax in a
      patient with the possibility of such exposure should raise the suspicion of
      malignant pleural mesothelioma.

PMID- 10893512
TI  - Re: The work dynamics of adults with asthma. 1999. Yelin E., Henke J. , Katz P.,
      Eisner M., Blanc P. Am. J. Ind. Med. 35:472-480.

PMID- 10893513
TI  - Laser-polarized (3)He as a probe for dynamic regional measurements of lung
      perfusion and ventilation using magnetic resonance imaging.
AB  - Magnetic resonance imaging (MRI) using laser-polarized noble gases, such as
      (129)Xe and (3)He, allows unparalleled noninvasive information on gas
      distribution in lung airways and distal spaces. In addition to pulmonary
      ventilation, lung perfusion assessment is crucial for proper diagnosis of
      pathological conditions, such as pulmonary embolism. Magnetic resonance perfusion
      imaging usually can be performed using techniques based on the detection of water
      protons in tissues. However, lung proton imaging is extremely difficult due to
      the low proton density and the magnetically inhomogeneous structure of the lung
      parenchyma. Here we show that laser-polarized (3)He can be used as a noninvasive
      probe to image, in a single MRI experiment, not only the ventilation but also the
      perfusion state of the lungs. Blood volume maps of the lungs were generated based
      on the (3)He signal depletion during the first pass of a superparamagnetic
      contrast agent bolus. The combined and simultaneous lung ventilation and
      perfusion assessments are demonstrated in normal rat lungs and are applied to an
      experimental animal model of pulmonary embolism. Magn Reson Med 44:1-4, 2000.

PMID- 10893515
TI  - Optimal voxel size for measuring global gray and white matter proton metabolite
      concentrations using chemical shift imaging.
AB  - Quantification of gray and white matter levels of spectroscopically visible
      metabolites can provide important insights into brain development and
      pathological conditions. Chemical shift imaging offers a gain in efficiency for
      estimation of global gray and white matter metabolite concentrations compared to
      single voxel methods. In the present study, the optimal voxel size is calculated
      from segmented human brain data and accompanying field maps. The optimal voxel
      size is found to be approximately 8 cc, but a wide range of values, 4-64 cc, can
      be chosen with little increase in estimated concentration error (<15%). Magn
      Reson Med 44:10-18, 2000.

PMID- 10893514
TI  - 1H decoupling for in vivo (19)F MRS studies using the time-share modulation
      method on a clinical 1.5 T NMR system.
AB  - Time-share modulation has been implemented successfully on a clinical 1.5 T
      nuclear magnetic resonance (NMR) system to perform in vivo (19)F[-(1)H]
      decoupling. It uses commercially available radiofrequency (RF) filters, a
      transistor-transistor logic (TTL)-controlled attenuator, and a double-resonant RF
      surface coil suitable for (19)F magnetic resonance spectroscopy (MRS) studies in
      vivo. This decoupling scheme gives a threefold improvement in signal-to-noise
      ratio performance compared with the conventional WALTZ-4 decoupling scheme, when
      significant interaction exists between the decoupler and the receiver. It can
      also eliminate receiver saturation (i.e., saturation due to coupling of the
      strong proton decoupling pulse to the (19)F coil) without the need for a high
      isolation coil system, thus allowing flexibility in coil geometry. This method
      has been demonstrated in vivo in patients receiving 5-fluorouracil chemotherapy.
      Magn Reson Med 44:5-9, 2000.

PMID- 10893516
TI  - NMR spectroscopy of single neurons.
AB  - The first spatially localized NMR spectra of osmolytes and metabolites from
      single isolated neurons have been obtained using a combination of high magnetic
      field strengths and NMR radio frequency (RF) microcoils. The proton spectra
      display peaks at high concentrations (100-300 mM) assigned to betaine and
      choline, and other metabolite resonances including lactate at lower
      concentrations in the order of 10s of millimoles. The volumes examined were
      approximately 10 nl, over two orders of magnitude less than previously possible.
      In these initial experiments; the cells were unperfused and the signal
      intensities of the osmolytes decrease with time, a phenomenon consistent with
      cell swelling. This work demonstrates the technical feasibility of NMR
      spectroscopy of single cells, further broadening the scope of NMR spectroscopy of
      living tissues from application to entire living organisms (man and animal
      models) and isolated tissues (perfused organs and cultured assemblies of cells)
      and now to single cells. Magn Reson Med 44:19-22, 2000.

PMID- 10893517
TI  - Fast echo planar based correlation-peak imaging: demonstration on the rat brain
      in vivo.
AB  - Two-dimensional correlation spectroscopy (2D-COSY) was combined with a fast echo
      planar based spectroscopic imaging technique in a new sequence. It can be
      optimized according to the coupling patterns of particular metabolites by using a
      constant time (CT) variant of COSY with chemical shift selective excitation and
      refocusing. Experiments were performed with an evolution time of 110 ms which was
      determined by simulating the CT-COSY experiment at several evolution times for
      the spin systems of myo-inositol (Ins) and taurine (Tau). The sequence has a
      minimum total measurement time of 17 min and was tested on a spherical phantom
      filled with a solution of Ins. The in vivo application of this method on the
      healthy rat brain demonstrates its improved spectral resolution as cross-peak
      signals from both Ins and Tau can be separated clearly. Magn Reson Med 44:23-28,
      2000.

PMID- 10893518
TI  - Temporal changes of cerebral metabolites and striatal lesions in acute 3
      nitropropionic acid intoxication in the rat.
AB  - To investigate the mechanisms of neuronal death in neurodegeneration, in vivo
      localized proton magnetic resonance spectroscopy ((1)H-MRS) and diffusion
      weighted MRI (DWI) were used to evaluate temporal changes in rat striata after
      administration of 3-nitropropionic acid. It was found that N-acetylaspartate
      (NAA) reduction, with nearly simultaneous evidence of striatal lesions in DWI,
      was preceded by a significant and progressive increase of acetate. Shortly before
      the NAA levels decreased to the lowest point, acetate levels peaked and began to
      gradually decline toward the control levels. These results suggest that acetate
      increase may arise from fatty acid degradation, inhibition of succinate
      dehydrogenase and possible NAA hydrolysis. The elevated acetate may provide a
      source of acetyl group for membrane repair during excitotoxic brain injury. Magn
      Reson Med 44:29-34, 2000.

PMID- 10893519
TI  - Measurements of human brain ethanol T(2) by spectroscopic imaging at 4 T.
AB  - Previous MRS measurements of ethanol in human brain have yielded a range of
      transverse relaxation times for ethanol methyl resonance at 1.5 T (200-380 ms).
      To determine the T(2) of the methyl proton resonance of ethanol in human brain, 8
      x 8 spectroscopic images were acquired at 16 different TE values. A frequency
      selective refocusing pulse was used to suppress J-modulation of the ethanol
      triplet, permitting nonintegral multiples of 1/J to be used for TE values. The
      measured T(2) values for the methyl resonances of ethanol, creatine, and N-acetyl
      aspartate in mixed tissues were 82 +/- 12, 148 +/- 20, and 227 +/- 25 ms,
      respectively. Regression analysis of the measured T(2) as a function of gray
      matter content indicates a shorter T(2) value for ethanol in pure white matter
      compared to that in pure gray matter. Magn Reson Med 44:35-40, 2000.

PMID- 10893520
TI  - Statistical artifacts in diffusion tensor MRI (DT-MRI) caused by background
      noise.
AB  - This work helps elucidate how background noise introduces statistical artifacts
      in the distribution of the sorted eigenvalues and eigenvectors in diffusion
      tensor MRI (DT-MRI) data. Although it was known that sorting eigenvalues
      (principal diffusivities) by magnitude introduces a bias in their sample mean
      within a homogeneous region of interest (ROI), here it is shown that magnitude
      sorting also introduces a significant bias in the variance of the sample mean
      eigenvalues. New methods are presented to calculate the mean and variance of the
      eigenvectors of the diffusion tensor, based on a dyadic tensor representation of
      eigenvalue-eigenvector pairs. Based on their use it is shown that sorting
      eigenvalues by magnitude also introduces a bias in the mean and the variance of
      the sample eigenvectors (principal directions). This required the development of
      new methods to calculate the mean and variance of the eigenvectors of the
      diffusion tensor, based on a dyadic tensor representation of eigenvalue
      eigenvector pairs. Moreover, a new approach is proposed to order these pairs
      within an ROI. To do this, a correspondence between each principal axis of the
      diffusion ellipsoid, an eigenvalue-eigenvector pair, and a dyadic tensor
      constructed from it is exploited. A measure of overlap between principal axes of
      diffusion ellipsoids in different voxels is defined that employs projections
      between these dyadic tensors. The optimal eigenvalue assignment within an ROI
      maximizes this overlap. Bias in the estimate of the mean and of the variance of
      the eigenvalues and of their corresponding eigenvectors is reduced in DT-MRI
      experiments and in Monte Carlo simulations of such experiments. Improvement is
      most significant in isotropic regions, but some is also observed in anisotropic
      regions. This statistical framework should enhance our ability to characterize
      microstructure and architecture of healthy tissue, and help to assess its changes
      in development, disease, and degeneration. Mitigating these artifacts should also
      improve the characterization of diffusion anisotropy and the elucidation of fiber
      tract trajectories in the brain and in other fibrous tissues. Magn Reson Med
      44:41-50, 2000. Published 2000 Wiley-Liss, Inc.

PMID- 10893521
TI  - Hybrid technique for dynamic imaging.
AB  - A number of data acquisition strategies have been introduced to speed up the
      image acquisition in dynamic settings. One such technique is the keyhole
      approach, which is based on reducing k-space coverage, and consequently the
      spatial resolution, of the dynamic information. Another is based on reducing the
      field of view of the dynamic information. These two techniques are complementary
      in that one reduces the field of view in k-space and the other does so in the
      spatial domain. A hybrid approach which combines the two is described in this
      study. In numerical simulations and experimental studies, this hybrid approach
      more accurately depicts the signal changes, outperforming the two techniques from
      which it is derived. Magn Reson Med 44:51-55, 2000.

PMID- 10893522
TI  - Active MR guidance of interventional devices with target-navigation.
AB  - This project incorporated a novel inductive coupling structure of three micro
      coils into an invasive device tip to determine both its tip position and
      orientation. Moreover, with the introduction of a new target-navigation technique
      the MR scan plane was defined automatically by the invasive device orientation
      and target tissue location. A time domain multiplexing technique was applied for
      simultaneous MR imaging and device tracking. Using these techniques, the acquired
      MR images always showed both the invasive device and its target tissue. Thus,
      roadmap images and their potential misregistration errors were avoided. A
      graphical user interface (GUI) was also designed to assist interventional
      physicians in monitoring and guiding the insertion of the interventional device.
      Ex vivo phantom and in vivo animal experiments were performed to test this new
      technique. The methods developed in this project provide a new active technique
      for interventional device guidance using MRI. Magn Reson Med 44:56-65, 2000.

PMID- 10893523
TI  - Estimation of pressure gradients in pulsatile flow from magnetic resonance
      acceleration measurements.
AB  - A method for estimating pressure gradients from MR images is demonstrated. Making
      the usual assumption that the flowing medium is a Newtonian fluid, and with
      appropriate boundary conditions, the inertial forces (or acceleration components
      of the flow) are proportional to the pressure gradients. The technique shown here
      is based on an evaluation of the inertial forces from Fourier acceleration
      encoding. This method provides a direct measurement of the total acceleration
      defined as the sum of the velocity derivative vs. time and the convective
      acceleration. The technique was experimentally validated by comparing MR and
      manometer pressure gradient measurements obtained in a pulsatile flow phantom.
      The results indicate that the MR determination of pressure gradients from an
      acceleration measurement is feasible with a good correlation with the true
      measurements (r = 0.97). The feasibility of the method is demonstrated in the
      aorta of a normal volunteer. Magn Reson Med 44:66-72, 2000.

PMID- 10893524
TI  - Detailed motion analysis of the left ventricular myocardium using an MR tagging
      method with a dense grid.
AB  - Detailed analysis of myocardial deformation through a whole cardiac cycle was
      accomplished using a tagging method with a high-density grid. Four sets of tagged
      images with a 4-mm-spacing grid were measured by generating four tagging pulses
      arranged at regular intervals in the cardiac cycle. Through each set of images,
      tag intersections were tracked semi-automatically. The estimated motions of tag
      intersections were concatenated so that sequential positions of myocardium were
      connected through a whole cardiac cycle. In vitro evaluation of the precision of
      this technique showed that the mean error of tracked 4-mm tag intersections was
      less than 0.47 +/- 0.17 mm, even on the quite low-contrast images, and the
      concatenation error caused by double concatenation was comparable to the
      interpolation error in the subendocardial area obtained with 8-mm tag
      intersection motion. The small difference between the two mean distance curves of
      the in vivo evaluation indicated that the method is useful for analyzing heart
      wall abnormalities. Magn Reson Med 44:73-82, 2000.

PMID- 10893525
TI  - Three-dimensional (87)Rb NMR imaging and spectroscopy of K(+) fluxes in normal
      and postischemic pig hearts.
AB  - K(+) uptake rates were measured in the anterior (An) and posterior (Pos) LV walls
      of pig hearts before and after regional ischemia and reperfusion using Rb(+) as a
      K(+) congener and 3D (87)Rb NMR imaging and spectroscopy as detection methods.
      The hearts were perfused by the Langendorff method with Krebs-Henseleit (KH)
      buffer and loaded with Rb(+) (4.7 mM, Rb-KH) after 120-min ischemia and 60-min
      reperfusion. A second protocol involved Rb(+) loading prior to ischemia. Ischemia
      was produced by occlusion of the left anterior descending artery, which after 110
      min of reperfusion resulted in infarction in the An wall (24 +/- 6% of the LV
      mass) determined by triphenyltetrazolium chloride staining. At the end of
      reperfusion pressure-rate product and oxygen consumption rate decreased to 58 +/-
      10 and 74 +/- 4% of their preischemic values, respectively. Phosphocreatine, ATP,
      and intracellular pH (pHi), measured by (31)P NMR spectroscopy in the infarcted
      area, decreased to 59 +/- 17, 32 +/- 6%, and 6.7 +/- 0.36 (from 7.05 +/- 0.13),
      respectively. Serial (87)Rb images were acquired according to both protocols.
      Rate constants (k x 10(3), min(-1)), relative amount of intracellular Rb(+) (A,
      %) and relative fluxes (F = kA, %/min) for the An and Pos walls were determined
      from the images. Before ischemia, F and k were comparable in the Pos and An
      walls. Ischemia + reperfusion decreased F in the An wall (from 4.4 +/- 0.3 to 1.4
      +/- 0.85) due to a decrease in A (20 vs. 73) and increased F in Pos wall (from
      3.2 +/- 0.6 to 6.6 +/- 0.23) due to an increase in k (from 42 +/- 3 to 93 +/- 6).
      The intensities of the Rb images correlated with the Rb(+) content measured in
      tissue samples. Magn Reson Med 44:83-91, 2000. Published 2000 Wiley-Liss, Inc.

PMID- 10893526
TI  - Noise reduction in 3D perfusion imaging by attenuating the static signal in
      arterial spin tagging (ASSIST).
AB  - Phase-encoded multishot SPIRAL approaches were used to acquire true 3D cerebral
      blood flow images of the human head using arterial spin tagging approaches.
      Multiple-inversion background suppression techniques, which suppress phase noise
      due to interacquisition fluctuations in the static magnetic field, reduced the
      temporal standard deviation of true 3D delta M images acquired using arterial
      spin tagging approaches by approximately 50%. Background suppressed arterial spin
      tagging (ASSIST) approaches were used to obtain high-resolution isotropic true 3D
      cerebral blood flow images, and to obtain true 3D activation images during
      cognitive (working memory) tasks. Magn Reson Med 44:92-100, 2000. Published 2000
      Wiley-Liss, Inc.

PMID- 10893527
TI  - Sampling and reconstruction effects due to motion in diffusion-weighted
      interleaved echo planar imaging.
AB  - Subject motion during diffusion-weighted interleaved echo-planar imaging causes k
      space offsets which lead to irregular sampling in the phase-encode direction. For
      each image, the k-space shifts are monitored using 2D navigator echoes, and are
      shown to lead to a frequent violation of the Nyquist condition when an ungated
      sequence is used on seven subjects. Combining data from four repeat acquisitions
      allows the Nyquist condition to be satisfied in all but 1% of images.
      Reconstruction of the irregularly-sampled data can be performed using a matrix
      inversion technique. The repeated acquisitions make the inversion more stable and
      additionally improve the signal-to-noise ratio. The resultant isotropic diffusion
      weighted images and average apparent diffusion coefficient (ADC) maps show high
      resolution and enable clear localization of a stroke lesion. Residual ADC
      artifacts with a slow spatial variation are observed and assumed to originate
      from non-rigid pulsatile brain motion. Magn Reson Med 44:101-109, 2000.

PMID- 10893528
TI  - Spreading waves of transient and prolonged decreases in water diffusion after
      subarachnoid hemorrhage in rats.
AB  - Diffusion-weighted MRI (DWI), which can detect cortical spreading depressions
      (SDs) as propagating waves of reduced apparent diffusion coefficient (ADC) of
      water, was used to investigate whether spreading depression occurs after
      subarachnoid hemorrhage (SAH) induced by endovascular perforation in the rat.
      Eleven rats underwent SAH while positioned in the magnet. The ADC measurements
      had a temporal resolution of 12 sec. Transient decreases in ADC to 74 +/- 5% of
      pre-SAH values were observed in three rats after SAH, which propagated over the
      cortex with an average speed of 4.2 +/- 0. 6 mm/min, consistent with an SD wave.
      Furthermore, in all 11 rats, a wavefront of reduced ADC, which did not resolve
      within the 12 min observation period, spread at a speed of 3.2 +/- 1.7 mm/min in
      the ipsilateral cortex, and again is consistent with the speed of SD propagation.
      Therefore, spreading depression-like cellular depolarization is a consequence of
      acute subarachnoid hemorrhage in rats. Magn Reson Med 44:110-116, 2000.

PMID- 10893529
TI  - Selecting an appropriate anisotropy index for displaying diffusion tensor imaging
      data with improved contrast and sensitivity.
AB  - A review of the behavior of different diffusion anisotropy indices (DAIs) to
      changes in diffusion anisotropy was undertaken and the limitations of several
      previously proposed DAIs are discussed. A mathematical representation of
      anisotropy sensitivity was used to enable image contrast and sensitivity to noise
      to be predicted. This technique was utilized to devise a new DAI, the gamma
      variate anisotropy, which has a low sensitivity to noise and an improved contrast
      range for human brain imaging. This index can be easily modified for other
      applications, in that the range of anisotropy values to which it is highly
      sensitive can be altered. Magn Reson Med 44:117-121, 2000.

PMID- 10893530
TI  - Improved estimation of velocity and flow rate using regularized three-point phase
      contrast velocimetry.
AB  - We improved the three-point phase-contrast method by regularization of MR
      velocity data after acquisition of a low velocity-to-noise ratio (VNR) velocity
      image and a high VNR aliased velocity image. The phase unwrapping algorithm is
      based on the assumed correlation of the velocity of adjacent flow voxels on the
      low VNR and the unaliased high VNR images. We used Fourier encoding with eight
      velocity-encoding gradient steps to obtain reference velocity images of the aorta
      from five subjects (274 images) and compared them with the phase-contrast and
      three-point phase-contrast images with and without regularization. The VNR of the
      regularized velocity image was improved by 9.1 dB and the VNR of the three-point
      phase-contrast velocity image was improved by 0.7 dB with respect to the low
      first moment velocity image. Corresponding improvements of 9 dB and 3.7 dB were
      obtained for the estimations of instantaneous flow rate. Magn Reson Med 44:122
      128, 2000.

PMID- 10893531
TI  - Critical sampling in ROSE scanning.
AB  - The acquisition of unaliased ROSE (Radially Oriented Sinusoidal Excursions in k
      space) data requires the appropriate selection of a gradient frequency, number of
      interleaves, and number of data samples per acquisition. When the data samples
      are uniformly distributed in time, they fall on irregularly spaced circles in k
      space. Aliasing due to radial undersampling will be eliminated when the number of
      sample circles equals the number of pixels in one dimension of the desired
      reconstructed image. Azimuthal aliasing will be completely eliminated when the
      total number of ROSE petals is four times the number of pixels in one dimension,
      but acceptable reconstructions may be had with fewer petals. Magn Reson Med
      44:129-136, 2000.

PMID- 10893532
TI  - Comparison of simultaneously measured perfusion and BOLD signal increases during
      brain activation with T(1)-based tissue identification.
AB  - Perfusion and blood oxygenation level-dependent (BOLD) signals were
      simultaneously measured during a finger-tapping task at 3T using QUIPSS II with
      thin-slice TI(1) periodic saturation, a modified pulsed arterial spin labeling
      technique that provides quantitative measurement of perfusion. Perfusion and BOLD
      signal changes due to motor activation were obtained and correlated with the T(1)
      values estimated from echo-planar imaging (EPI)-based T(1) maps on a voxel-by
      voxel basis. The peak perfusion signal occurs in voxels with a T(1) of brain
      parenchyma while the peak BOLD signal occurs in voxels with a T(1) characteristic
      of blood and cerebrospinal fluid. The locations of the peak signals of functional
      BOLD and perfusion only partially overlap on the order of 40%. Perfusion
      activation maps will likely represent the sites of neuronal activity better than
      do BOLD activation maps. Magn Reson Med 44:137-143, 2000.

PMID- 10893533
TI  - NMR relaxation in tissues with weak magnetic inhomogeneities.
AB  - A theory is presented for describing the effect on the transverse NMR relaxation
      rate of microscopic spatial inhomogeneities in the static magnetic field. The
      theory applies when the inhomogeneities are weak in magnitude and the nuclear
      spins diffuse a significant distance in comparison with a length scale
      characterizing the inhomogeneities. It is shown that the relaxation rate is
      determined by a temporal correlation function and depends quadratically on the
      magnitude of the inhomogeneities. For the case of unrestricted diffusion, a
      simple algebraic approximation for the temporal correlation function is derived.
      The theory is illustrated by applying it to a model of randomly distributed
      magnetized spheres. The theory is also used to fit experimental data for the
      dependence of the relaxation rate on the interecho time for a Carr-Purcell
      Meiboom-Gill pulse sequence. The experimental systems considered are in vitro red
      blood cell suspensions and samples of human gray matter and rat liver. Magn Reson
      Med 44:144-156, 2000.

PMID- 10893534
TI  - Direct histological validation of diffusion tensor MRI in formaldehyde-fixed
      myocardium.
AB  - Diffusion tensor MRI is emerging as a rapid, nondestructive method to map
      myocardial fiber organization. It accurately measures myofiber orientation in
      hearts bathed in or perfused with cardioplegic solution. This study shows it also
      accurately maps the fibrous architecture of formalin-fixed hearts. Fiber
      orientations obtained by MRI and histology at the same locations in an excised
      portion of rabbit ventricle differed on average by 3.7 degrees (SD = 6.4 degrees,
      N = 70), a closer correspondence than achieved with previous preparations. The
      longer acquisition times afforded by fixed-heart imaging provides better
      accuracy, and should enable high-resolution reconstruction of the entire
      ventricular architecture. Magn Reson Med 44:157-161, 2000.

PMID- 10893535
TI  - Image-based method for retrospective correction of physiological motion effects
      in fMRI: RETROICOR.
AB  - Respiration effects and cardiac pulsatility can induce signal modulations in
      functional MR image time series that increase noise and degrade the statistical
      significance of activation signals. A simple image-based correction method is
      described that does not have the limitations of k-space methods that preclude
      high spatial frequency correction. Low-order Fourier series are fit to the image
      data based on time of each image acquisition relative to the phase of the cardiac
      and respiratory cycles, monitored using a photoplethysmograph and pneumatic belt,
      respectively. The RETROICOR method is demonstrated using resting-state
      experiments on three subjects and compared with the k-space method. The method is
      found to perform well for both respiration- and cardiac-induced noise without
      imposing spatial filtering on the correction. Magn Reson Med 44:162-167, 2000.

PMID- 10893537
TI  - Isn't combinatorial chemistry just chemistry?

PMID- 10893536
TI  - Temperature mapping using the water proton chemical shift: self-referenced method
      with echo-planar spectroscopic imaging

PMID- 10893538
TI  - Money matters?

PMID- 10893539
TI  - Protein markers for psychiatric disorders suggest new treatment strategies.

PMID- 10893540
TI  - Complement activation in myocardial infarction: a target for future treatments?

PMID- 10893542
TI  - Untangling Alzheimer's disease with beta-secretase inhibitors.

PMID- 10893541
TI  - SNPs; windows of opportunity in the human genome.

PMID- 10893544
TI  - New PDE5 inhibitors: more selective than Viagra?

PMID- 10893543
TI  - Transforming innovation and commercialization in drug discovery.

PMID- 10893546
TI  - The in silico world of virtual libraries.
AB  - Combinatorial chemistry has provided medicinal chemists with an unprecedented
      ability to synthesize large numbers of molecules. However, early experience was
      that this did not result in any increase in the number of real candidates for
      lead optimization. Attention has increasingly focussed on the use of
      computational techniques for the design of combinatorial libraries. This review
      will describe some of the issues that have been considered in this area and
      discuss some of the possible developments in the near future.

PMID- 10893547
TI  - Inhibition of tumor angiogenesis by synthetic receptor tyrosine kinase
      inhibitors.
AB  - Protein tyrosine kinases have emerged as crucial targets for therapeutic
      intervention in cancer. More recently, growth factor ligands and their respective
      receptor tyrosine kinases (RTKs) have been shown to be required for tumor cell
      growth. This latter aspect includes tumor angiogenesis where the growth of tumors
      leads to compensatory effects on host cells in the tumor microenvironment leading
      to the growth of microvessels. The purpose of this review is to focus on
      synthetic chemical approaches to block RTKs associated with tumor angiogenesis as
      a means to limit the growth and spread of human tumors.

PMID- 10893548
TI  - Can peptides be mimicked?
AB  - The biological activity of peptides is of enormous interest to the pharmaceutical
      industry, but endogenous peptides themselves typically have some limitations
      regarding bioavailability and oral activity. Peptide mimicry by design used to be
      touted as a solution to these problems and was focused on impersonating secondary
      structural motifs, particularly beta-turns, but this approach has yielded few
      pharmaceutical products. Today, the process of identifying and optimizing peptide
      mimics is driven mainly by screening to obtain hits, followed by optimization,
      which might include design based on arranging pharmacophores appropriately in
      three dimensions. A consequence of this is that one of the more difficult
      problems in drug discovery, namely the identification of non-peptide agonists at
      peptide receptors, is beginning to be solved.

PMID- 10893549
TI  - Designing chiral libraries for drug discovery.
AB  - Identification of new biological targets combined with combinatorial medicinal
      chemistry has enormous potential to facilitate the discovery of new therapeutics.
      However, these new targets might require the use of different or more complex
      screening libraries. This complexity might be achieved through the use of new
      templates or the identification of new chemistries. One approach is the use of
      chiral libraries that have been designed using three-dimensional pharmacophore
      and shape descriptors to provide maximal structure-activity information after
      screening. The advantages of using a designed chiral library in primary screening
      and the information one should obtain are discussed.

PMID- 10893551
TI  - Combinatorial chemistry.

PMID- 10893550
TI  - Monitor: molecules and profiles.
AB  - Monitor provides an insight into the latest developments in drug discovery
      through brief synopses of recent presentations and publications together with
      expert commentaries on the latest technologies. There are two sections: Molecules
      summarizes the chemistry and the pharmacological significance and biological
      relevance of new molecules reported in the literature and on the conference
      scene; Profiles offers commentary on promising lines of research, emerging
      molecular targets, novel technology, advances in synthetic and separation
      techniques and legislative issues.

PMID- 10893552
TI  - Can you work?

PMID- 10893553
TI  - Rotator cuff injuries.
AB  - Different types of rotator cuff injuries frequently present to Accident and
      Emergency departments and minor injury units but can be difficult to
      differentiate clinically. This brief case study describes the examination and
      diagnosis of related shoulder injuries, specifically rotator cuff
      tears/disruption and calcifying supraspinatus tendinitis. The relevant anatomy
      and current therapies for these injuries is also discussed to enable the
      emergency nurse practitioner to have a greater understanding of the theory
      surrounding their diagnosis and treatments.

PMID- 10893554
TI  - Expert evidence: do you have all the facts?
AB  - As a practising expert witness, or an accident and emergency nurse considering
      the move into the challenging world of litigation, do you have all the facts
      about expert evidence to hand? What is your role in the proceedings? When could
      you be sued for the advice you give? Should you ever accept a case on a no-win,
      no-fee basis?

PMID- 10893555
TI  - Firearms in A&E.

PMID- 10893556
TI  - Flight nursing down under: a perspective.
AB  - The purpose of this paper is to describe in the broadest sense the scope of
      flight nursing practice in the Western Australian context. The Royal Flying
      Doctor Service--Western Operations provides aeromedical and associated health
      services, through primary health clinics to persons living in remote and rural
      areas of Western Australia. Flight nurses provide a significant contribution to
      fulfilling the core business of the Royal Flying Doctor Service, and in doing so
      demonstrate that they are able to combine the diversity and speciality that is
      flight nursing, with the challenges not only of the aviation environment, but of
      the diversity and remoteness of the physical environment that they may find
      themselves in.

PMID- 10893557
TI  - Patient satisfaction with a new nurse practitioner service.
AB  - In the UK the role of the Nurse Practitioner (NP) has been slower to develop than
      in the USA (Tye 1997). However, since its inception, studies of the role have
      found positive results in areas of patient satisfaction (Touche Ross 1994). James
      and Pyrgos (1989) reported 94% of patients suitable to seen by a NP would use a
      NP if introduced. A study by Freij et al. (1996) concluded that emergency NPs
      were as competent at interpreting X-rays as casualty officers. Despite such
      evidence, Meek et al. (1995) noted opposition to this new advanced practice from
      other disciplines who wished to maintain the 'status quo'. In light of these
      findings, a study was undertaken to examine the new NP Service at Antrim
      Hospital, Northern Ireland. A patient satisfaction survey, a retrospective X-ray
      audit and a subjective assessment by other disciplines, were carried out in order
      to evaluate the service.

PMID- 10893558
TI  - A case-control study of the transit times through an accident and emergency
      department of ankle injured patients assessed using the Ottawa Ankle Rules.
AB  - This paper reports part of a larger study of 354 consecutive attendances to an
      Accident and Emergency department by patients with ankle injuries. One hundred
      and ninety-nine patients met the criteria for inclusion in this study. The case
      study group (n =79) were those patients assessed by a nurse practitioner who had
      been trained in, and had authority to use of the Ottawa Ankle Rules (OAR) and
      were referred for radiographs from triage assessment. The control group
      (initially 120) consisted of those patients who were assessed by nurses who were
      not trained to be nurse practitioners and were not empowered to use the OAR but
      were sent for radiographs when assessed at the treatment stage. Sixteen patients
      were excluded from the study due to missing time data, reducing the control group
      to 104 patients. Previous studies have suggested that reductions in transit times
      through the department can be achieved by empowering nurses to request
      radiographs at the time of initial assessment, although these studies did not
      look specifically at the application of the OAR. Significant reductions in
      transit time are demonstrated for those patients who are required to have an X
      ray to confirm a diagnosis if this is requested at the time of the triage
      assessment by nurse practitioners.

PMID- 10893559
TI  - Teenage pregnancy: an update.
AB  - In 1999 the DOH set a target to reduce conceptions in under 18s by 50% by the
      year 2010. In this the Government, supported by the Children Act (1989),
      highlighted the fact that it would be the responsibility of every health care
      professional and local authority to help achieve this goal. This paper discusses
      current issues in relation to teen pregnancies, dispels popular misconceptions
      and suggests ways in which Accident and Emergency nurses can contribute.

PMID- 10893560
TI  - An update on NHS direct.

PMID- 10893561
TI  - Surviving emergency social work: experience of an Australian Accident & Emergency
      Department.

PMID- 10893562
TI  - The forgotten heart of care: a model of spiritual care in the National Health
      Service.
AB  - Answering the spiritual as well as religious needs of patients has for years been
      seen as the province of the hospital chaplain, because spirituality has been
      regarded as the province of religion. As chaplains in the NHS we hope in this
      paper to raise awareness of the importance of spiritual care in the health
      service as a whole. Although there seems to be a large amount of interest in this
      area there are few tangible means of identifying and assessing spiritual need.
      Within the limits of this paper we aim to define spiritual care, to outline how
      we can identify spiritual distress, and suggest ways of evaluating spiritual
      care. Although we realise the difficulty of the task, we wish to 'Transcend
      vagueness and come to a more comfortable understanding of spirituality.' (Price
      et al 1995)

PMID- 10893563
TI  - Suicide risk assessment: a review of procedures.
AB  - Suicide risk assessment is an important part of the nurse's role. Suicide
      screening is an integral component of the assessment process. It should be
      systematic and follow a prescribed procedure: client self assessment, holistic
      assessment and diagnosis. The Gatehouse Assessment Centre in Warrington, UK, a
      predominantly nurse led centre, was opened in 1995, operates 365 days, 9 am till
      9 pm, with open referral. The Centre offers psychiatric assessment, short-term
      treatments or referral on without hospital beds. In line with local and national
      policy, the Gatehouse team have introduced suicide rating scales as part of their
      risk screening process. However, the team have encountered problems using their
      designated scale, adapted from the Suicide Intent Scale, Pierce (1981). The major
      problem with the use of a rating scale was that, as a one off scoring system, it
      did not reflect the dynamic nature of suicidal behaviour. Furthermore, it is
      questionable whether a tool developed for research purposes would be used in the
      same way in practice. From a clinical perspective, the tool was capable of
      measurement only and failed to assist a dynamic holistic assessment required by
      practitioners. It was, therefore, necessary to review and evaluate the risk
      assessment procedure. In order to address these problems an assessment procedure
      which is more than a once only 'score' was piloted. The procedure incorporated
      risk screeners. Rather than rely on a value weighting system, or a positive or
      negative conclusion, it took account of the continuum of risk which is contingent
      on a broad range of factors. It took account of the accumulation of risk factors
      which may be increased or reduced in the light of unfolding events. Details of
      the new procedure, how it has been incorporated into the assessment process and
      subsequent management plan, and methodological considerations for further study
      are detailed.

PMID- 10893567
TI  - Clinical management of foreign bodies of the genitourinary tract.
AB  - PURPOSE: The variety of foreign bodies inserted into or externally attached to
      the genitourinary tract defies imagination and includes all types of objects. The
      frequency of such cases renders these objects an important addition to the
      diseases of the urinary organs. MATERIALS AND METHODS: We performed a
      computerized MEDLINE search followed by a manual bibliographic review of cross
      references. These reports were analyzed and the important findings summarized.
      RESULTS: Our review encompassed approximately 800 single case reports on foreign
      bodies in the English world literature published between 1755 and 1999. We
      structured the range of introduced objects, by referring to origin and material
      as well as the genitourinary organs involved. Furthermore, we noted
      symptomatology and diagnoses, including psychological involvement, as well as
      possible treatment options. CONCLUSIONS: The most common motive associated with
      foreign bodies of the genitourinary tract is sexual or erotic in nature. The most
      suitable method of removing a urethral foreign body depends on the size and
      mobility of the object applied to the genitourinary tract. When possible,
      endoscopic and minimal invasive techniques of removal should be used. However,
      surgical retrieval of a foreign body may be required, particularly when there is
      a severe associated inflammatory reaction.

PMID- 10893568
TI  - The orthotopic Kock ileal neobladder: functional results, urodynamic features,
      complications and survival in 166 men.
AB  - PURPOSE: We report our experience with 166 patients who underwent radical
      cystectomy and orthotopic bladder substitution with the ileal Kock neobladder
      between February 1990 and January 1999. MATERIALS AND METHODS: We classified
      complications as early (3 months or less postoperatively) and late. Continence
      was assessed by patient interview, the need to use protective devices and
      provocative incontinence testing. Neobladder function was evaluated by
      uroflowmetry, post-void residual urine volume measurement and enterocystometry,
      and renal function was assessed by 51creatinine ethylenediaminetetraacetic acid
      clearance. RESULTS: There were no perioperative deaths. However, 52 early
      complications developed in 39 patients (23.5%) and 73 late complications in 62
      (37.4%). The rate of early and late complications associated with the urinary
      tract was 11.5% and 23.5% with abdominal reoperation rates of 1.8% and 2.4%,
      respectively, due to these complications. At 3 and 5 years the risk of stone
      formation on the metallic staples was 18% and 34%, and the risk of B12 deficiency
      was 30% and 33%, respectively. One patient (0.6%) underwent reoperation for
      ureteral anastomotic stricture. Anterior urethral stricture in 5 cases (3%) was
      caused by recurrence in 1 and urethral anastomotic stricture in 1 also resulted
      from recurrent disease. Daytime continence was reported by 97% and 100% of our
      patients at 1 and 5 years, respectively. Provocative incontinence testing
      confirmed this level of daytime continence. Overall 75% of patients reported
      nighttime continence at 1 year and 94% at 5 years. The need for a nighttime
      protective device decreased with time. At 1 versus 3 years 39.8% versus 45.9% of
      patients used no protection, 29.7% versus 39.2% used a sanitary pad and 30.5%
      versus 14.9% used a condom device. Enterocystometric capacity and subtracted
      maximum reservoir pressure remained remarkably uniform at 456 versus 411 ml. and
      47 versus 50 cm. water 6 months and 5 years postoperatively, respectively.
      Nevertheless, median post-void residual urine volume increased from 20 ml. at 6
      months to 40 ml. at 5 years with an increased prevalence of patients requiring
      intermittent catheterization due to post-void residual urine greater than 100 ml.
      from 16% at 6 months to 44% at 5 years. 51Creatinine ethylenediaminetetraacetic
      acid clearance remained unchanged. There was a substantial 5-year survival
      advantage for the subpopulation with stage pT3a or less, pN0 tumors (94% versus
      51%, p <0.001). CONCLUSIONS: Radical cystectomy and orthotopic bladder
      substitution with the Kock ileal neobladder may be performed with an acceptable
      complication rate and good functional results. The probability of survival was
      considerably higher for patients with tumor confined to the bladder. Consequently
      we believe that early aggressive treatment should be considered in those with
      invasive disease, and reconstruction with orthotopic bladder substitution may
      encourage patients to accept radical surgery.

PMID- 10893569
TI  - Pheochromocytoma coexisting with renal artery lesions.
AB  - PURPOSE: Physiologically significant renal artery lesions in the presence of a
      pheochromocytoma comprise a confounding factor which may impact on the
      hypertension cure following excision of the pheochromocytoma. We present 10 cases
      of these dual lesions and review the literature on this entity. MATERIALS AND
      METHODS: From 1952 to 1999, 269 patients were diagnosed with pheochromocytoma at
      our institution. Hospital charts of these patients were reviewed retrospectively
      to identify those with coexisting renal artery stenosis. A Medline search was
      performed to review the available literature. RESULTS: Of the 269 patients with
      pheochromocytoma 10 (3. 7%) had coexisting renal artery lesions, including renal
      artery stenosis in 8, renal artery aneurysm in 1 and postangiographic dissection
      occlusion in 1. Pheochromocytoma was adrenal in 8 cases and ectopic in 2. Of the
      patients 9 have been treated to date by adrenalectomy in 4, nephroadrenalectomy
      in 3, adrenalectomy plus lysis of renal artery adhesions in 1 and adrenalectomy
      plus renal autotransplantation with bench repair in 1. Both lesions were
      diagnosed preoperatively in 9 cases and a hypovascular adrenal lesion was missed
      preoperatively in 1. A review of literature revealed a total of 87 cases of
      coexisting pheochromocytoma and renal artery lesions. CONCLUSIONS: There are
      multiple mechanisms that can lead to renal artery stenosis and pheochromocytoma.
      A high index of suspicion is necessary to enable both entities to be diagnosed
      preoperatively and allow proper planning of surgical therapy. Incomplete
      diagnosis may lead to persistent hypertension postoperatively.

PMID- 10893570
TI  - Relationship of frequency, age, sex, stone weight and composition in 15,624
      stones: comparison of resutls for 1980 to 1983 and 1995 to 1998.
AB  - PURPOSE: We studied the relationship of stone frequency and composition to age,
      sex and stone weight. MATERIALS AND METHODS: A retrospective study was performed
      of all 15,624 stones submitted for analysis with infrared and wet chemical
      methods in Newfoundland and Labrador from 1979 to 1998. RESULTS: There were 1,067
      bladder stones of which 216 contained magnesium ammonium phosphate. The remaining
      14,557 stones were from the kidney and ureter, and 11,707 were composed only of
      calcium oxalate and/or phosphate. Of the remaining 2,850 kidney and ureter stones
      magnesium ammonium phosphate was present in 573, uric acid/urate without
      magnesium ammonium phosphate in 1,109 and other compounds in 1,168. The 11,707
      oxalate phosphate group was subdivided by infrared peak analysis based on oxalate
      to-phosphate ratio into phosphate-ratio 1 or less, intermediate-1 to 10 and
      oxalate-10+. Oxalate comprised 65% of the 11,707 stones compared to 16% for
      phosphate. Women submitted 52% of phosphate stones compared with 28% of oxalate
      stones. From the first (1980 to 1983) to the last (1995 to 1998) complete 4-year
      study periods, there was a relative increase in oxalate and decrease in phosphate
      stones, associated with increasing age from decades 5 to 6 for oxalate and
      phosphate stones, except that the age peak for phosphate stones in women remained
      in decade 3. Median weight of 1, 828 phosphate stones was 43 mg. (mean 234)
      compared with 25 mg. (mean 98) for 7,634 oxalate stones. Male-to-female ratio was
      0.91 for phosphate stones compared with 2.62 for oxalate stones. CONCLUSIONS:
      Phosphate stones were on average heavier and relatively more common in women, had
      an earlier age peak frequency in women than oxalate stones and became less
      frequent during our last 4-year study period. In contrast, oxalate stones were
      much more common, of lighter weight and became more frequent with time.

PMID- 10893571
TI  - Plain abdominal x-ray versus computerized tomography screening: sensitivity for
      stone localization after nonenhanced spiral computerized tomography.
AB  - PURPOSE: Urolithiasis followup with plain abdominal x-ray requires adequate
      visualization of the calculus on the initial x-ray or computerized tomography
      (CT) study. We compared the sensitivity of plain abdominal x-ray versus CT for
      stone localization after positive nonenhanced spiral CT. MATERIALS AND METHODS:
      We evaluated 46 consecutive nonenhanced spiral CT studies positive for upper
      urinary tract lithiasis for which concurrent plain abdominal x-rays were
      available. X-ray and CT studies were compared for the ability to visualize
      retrospectively a stone given its location by CT. A consensus of 1 radiologist
      and 3 urologists was reached in each case. Cross-sectional stone size and maximum
      length were measured on plain abdominal x-ray. RESULTS: Plain abdominal x-ray and
      scout CT had 48% (22 of 46 cases) and 17% (8 of 46) sensitivity, respectively,
      for detecting the index stone (p <0.00004). Of the 39 stones overall visualized
      on plain abdominal x-ray only 19 (49%) were visualized on scout CT. Mean cross
      sectional area and length of the stones on scout CT were 0.34 cm.2 (approximately
      6 x 5.5 mm.) and 6. 5 mm., respectively, while the average size of those missed
      was 0.11 cm.2 (approximately 4 x 3 mm.) and 3.6 mm. The mean size differences in
      the groups were highly significant (p <0.0009). CONCLUSIONS: Plain abdominal x
      ray is more sensitive than scout CT for detecting radiopaque nephrolithiasis. Of
      the stones visible on plain abdominal x-ray 51% were not seen on CT. To
      facilitate outpatient clinic followup of patients with calculi plain abdominal x
      ray should be performed when a stone is not clearly visible on scout CT.

PMID- 10893572
TI  - Intracranial aneurysms and autosomal dominant polycystic kidney disease: followup
      study by magnetic resonance angiography.
AB  - PURPOSE: Intracranial aneurysms are known to complicate autosomal dominant
      polycystic kidney disease. We assess the value of magnetic resonance angiography
      to detect intracranial aneurysms early in patients with autosomal dominant
      polycystic kidney disease. MATERIALS AND METHODS: We evaluated 15 patients with
      asymptomatic autosomal dominant polycystic kidney disease treated at our hospital
      between 1992 and 1998. Magnetic resonance angiography was performed at
      presentation and was repeated 18 to 72 months after treatment. RESULTS: On the
      initial magnetic resonance angiogram 3 intracranial aneurysms were detected in 3
      patients. The intracranial aneurysms ranged from 4 to 8 mm. in diameter, and were
      in the anterior communicating artery in 1, in the vertebral artery in 1, and at
      the bifurcation of the internal carotid artery and ophthalmic artery in 1 case.
      Repeat magnetic resonance angiography 18 to 72 months after treatment revealed
      new intracranial aneurysms in 2 patients. In 1 case the lesion was 7 mm. in
      diameter, in the internal carotid artery and posterior communicating artery, and
      detected 69 months after the initial angiogram. In the other patient the lesion
      was 4 mm. in diameter, in the anterior communicating artery and detected 71
      months after treatment. CONCLUSIONS: Since new intracranial aneurysms were
      demonstrated in patients followed for a long time periodic repeat magnetic
      resonance angiography is important.

PMID- 10893573
TI  - Hand assisted laparoscopic radical nephrectomy for renal carcinoma using a new
      abdominal wall sealing device.
AB  - PURPOSE: We report our initial experience with a hand assisted laparoscopic
      radical nephrectomy for patients with renal carcinoma, and compare our results to
      those of conventional open radical nephrectomy. MATERIALS AND METHODS: The
      clinical data on 6 consecutive patients who underwent hand assisted laparoscopic
      radical nephrectomy for stage T1N0M0 renal cell carcinoma were reviewed. We
      performed hand assisted laparoscopic surgery using the new LAP DISC* abdominal
      wall sealing device. We compared the results of this procedure with those of
      conventional open radical nephrectomy in 12 patients with stage T1N0M0 renal cell
      carcinoma. RESULTS: The hand assisted laparoscopic radical nephrectomy for renal
      carcinoma was successfully performed without any major or minor complications in
      all 6 patients. Mean operation time for the laparoscopic group was significantly
      longer than that for the open surgery group (303 minutes versus 224 minutes, p =
      0.0042). However, no significant difference was observed in mean estimated blood
      loss for the 2 groups (264 ml. in the laparoscopic group versus 341 ml. in the
      open surgery group). The frequency of parenteral analgesia postoperatively in the
      laparoscopic group was significantly lower than that in the open surgery group
      (16.7% versus 75.0%, p = 0.043). In addition, the laparoscopic group seemed to
      recover more rapidly than the open surgery group. The abdominal wall sealing
      device was easy to attach to the abdominal wall, and allowed rapid hand removal
      and reinsertion. CONCLUSIONS: Our preliminary results indicate that a hand
      assisted laparoscopic radical nephrectomy with the abdominal wall sealing device
      is an effective and safe surgical procedure, and is less invasive than open
      radical nephrectomy.

PMID- 10893574
TI  - Endovascular gastrointestinal stapler device malfunction during laparoscopic
      nephrectomy: early recognition and management.
AB  - PURPOSE: Controlled ligation and division of the renal hilum are critical steps
      during any nephrectomy procedure. The use of the endovascular gastrointestinal
      anastomosis (GIA) stapling device for control of the renal vessels during
      laparoscopic nephrectomy has become standard practice. However, malfunction can
      lead to serious consequences which require emergency conversion to an open
      procedure. We report our experience with GIA malfunction during laparoscopic
      nephrectomy. MATERIALS AND METHODS: From July 1993 to September 1999, 565
      patients underwent laparoscopic nephrectomy at 2 institutions for benign and
      malignant diseases, and for live renal donation. Retrospective chart reviews and
      primary surgeon interviews were conducted to determine etiology of failure,
      intraoperative management and possible future prevention. RESULTS: Malfunction
      occurred in 10 cases (1.7%). In 8 cases the renal vein was involved and
      malfunctions affected the renal artery in 2. The estimated blood loss ranged from
      200 to 1,200 cc. Open conversions were necessary in 2 cases (20%). The etiology
      of the failure included primary instrument failure in 3 cases and preventable
      causes in 7. Open surgery was required in 2 patients and laparoscopic management
      was possible in 8. CONCLUSIONS: The endovascular GIA stapler is useful in
      performing laparoscopic nephrectomy. However, malfunctions may occur, and can be
      associated with significant blood loss and subsequent need for conversion to an
      open procedure. The majority of errors could be avoided with careful application
      and recognition. Many failures, especially when recognized before release of the
      device, can be managed without conversion to an open procedure.

PMID- 10893575
TI  - Outcome of isolated renal cell carcinoma fossa recurrence after nephrectomy.
AB  - PURPOSE: Local recurrence of renal cell carcinoma in the renal fossa after
      complete radical nephrectomy is uncommon. We characterize and determine outcome
      in a small subset of patients. MATERIALS AND METHODS: From 1970 to 1998 the
      incidence of isolated renal bed recurrence among 1,737 T1-3N0M0 unilateral
      nephrectomy cases was 1. 8% (standard error [SE] 0.4) at 5 years. There were 30
      patients in whom isolated local fossa carcinoma recurred after complete radical
      nephrectomy without evidence of metastatic disease. Patients with any nodal
      involvement at radical nephrectomy were excluded from study as were those who had
      undergone any form of partial nephrectomy. Patient charts were reviewed for
      clinical presentation, stage, treatment, development of metastatic disease and
      survival. Pathological stage was assigned according to the 1997 TNM staging
      system. Recurrence was identified in 12 (40%) patients during routine followup
      and the remaining 18 (60%) presented with symptoms related to the recurrent
      tumor. Patients were divided into 3 treatment groups of observation (9), therapy
      excluding surgical extirpation (11) and complete surgical resection alone or in
      conjunction with additional therapy (10). Mean time from local recurrence to
      development of metastatic disease was calculated. Survival from local recurrence
      to overall death and disease specific death was estimated using the Kaplan-Meier
      method. Survival curves for the different treatment groups were then compared.
      RESULTS: There were 30 patients identified with an ipsilateral renal fossa
      recurrence of renal cell carcinoma after complete nephrectomy in the absence of
      disseminated disease. Mean followup was 3.3 years (range 0.006 to 14.8) and no
      patient was lost to followup. The T stage of the primary tumor was T1/T2 in 13
      cases, T3a in 4, T3b in 12, and T3c in 1, and all were node negative. Mean time
      to metastasis was 1. 6 years (range 0.006 to 7.3) in the 19 patients who had
      documented interval metastatic disease after local recurrence. There were 26
      deaths, of which 25 were disease specific. Estimated overall crude and cause
      specific survival at 1 and 5 years was 66% and 28%, respectively. Calculating
      survival among symptomatic and asymptomatic patients revealed no discernible
      difference in outcome (p = 0.94). The 5-year survival rate with surgical
      resection was 51% (SE 18) compared to 18% (12) treated with adjuvant medical
      therapy and only 13% (12) with observation alone. The differences in cause
      specific survival were significant (p </=0.02). CONCLUSIONS: Isolated local
      recurrence is rare with less than a 2% incidence at 5-year followup. Presently
      long-term survival with locally recurrent renal cell carcinoma is poor with a 28%
      survival rate at 5 years. However, patients who underwent surgical resection had
      an improved 5-year cause specific survival rate of 51% compared to 18% treated
      with adjuvant medical therapy and 13% with observation alone. This finding
      suggests that select patients may benefit from an aggressive surgical approach.

PMID- 10893576
TI  - Prediction of spontaneous ureteral calculous passage by an artificial neural
      network.
AB  - PURPOSE: Although a consensus exists that small stones presenting in the distal
      ureter have a good probability of spontaneous passage, it is difficult to predict
      in individuals whether a particular ureteral stone would pass or require
      intervention. If an accurate judgment were made at presentation on the likelihood
      of stone passage, patients would receive immediate intervention for the stone or
      be notified of a more appropriate time at which to expect passage. We used an
      artificial neural network to evaluate data in patients with ureteral calculi to
      predict whether a stone would pass spontaneously or require intervention.
      MATERIALS AND METHODS: Data were collected from the records of 181 patients
      presenting with colic due to a ureteral calculus. Patient input factors included
      age, sex, race, marital status, insurance, stone side, level and size,
      hydronephrosis and obstruction grades, duration of symptoms before presentation,
      serum creatinine, history of stone passage or intervention and nausea, vomiting
      or fever. Outcomes evaluated were stone passage or intervention. Data were
      entered into a neural network created using commercially available computer
      software. RESULTS: A set of 125 patients from the database was used for training
      the network. The network correctly predicted outcome in 38 of the remaining 55
      patients (76%) used for testing. In the 25 cases in which stones passed
      spontaneously sensitivity was 100%. Duration of symptoms before presentation was
      the most influential factor in network ability to predict accurately stone
      passage, followed by hydronephrosis grade. CONCLUSIONS: An artificial neural
      network may be used to predict accurately the probability of spontaneous ureteral
      stone passage. Using such a model at presentation may help to determine whether a
      patient should receive early intervention for a stone or expect a lengthy
      interval before stone passage.

PMID- 10893577
TI  - Endoscopic management of impacted ureteral stones using a small caliber
      ureteroscope and a laser lithotriptor.
AB  - PURPOSE: We reviewed our experience with retrograde endoscopy using a small
      caliber ureteroscope and a laser lithotriptor in 104 consecutive patients with
      impacted ureteral stones and also analyzed the associated endoscopic findings.
      MATERIALS AND METHODS: From July 1993 to October 1999 we performed retrograde
      endoscopic treatment in 104 patients with impacted ureteral stones. Average
      maximum stone diameter was 15.2 mm. (range 2 to 110), and 9 patients had stones
      larger than 3 cm. Mean duration of impaction was more than 14 months and the
      longest was 10 years. We used 6.9Fr rigid or 6.9 to 7.5Fr flexible ureteroscopes
      and a pulsed dye laser or holmium:YAG laser lithotriptor. RESULTS: Of the 104
      ureteral stones 100 (96.2%) were completely fragmented by a single endoscopic
      procedure. Although 1 uric acid stone could not be disintegrated by either the
      pulsed dye laser or electrohydraulic lithotripsy early in this series, it was
      discharged spontaneously 2 weeks after the procedure. Additional extracorporeal
      shock wave lithotripsy (ESWL*) was required in 3 patients who initially had
      stones larger than 3 cm. A month after treatment no patient had evidence of
      residual stones. Using adjuvant ESWL a 100% success rate was attained with
      minimal morbidity. Endoscopic observation revealed inflammatory polyps of the
      ureter in 22 patients (21.2%), and stricture adjacent to the stone in 16 (15.
      4%). There were no significant complications. CONCLUSIONS: Using a small caliber
      ureteroscope and a laser lithotriptor we could treat the target stone in all 104
      patients with adjuvant ESWL in 3 cases. Endoscopic lithotripsy seems to be
      effective first line therapy for chronically impacted stones which are frequently
      associated with chronic inflammation, polyps and strictures, and avoids the
      futile repetition of ESWL and problems related to the prolonged passage of stone
      fragments.

PMID- 10893578
TI  - Endoscopic ureteroureterostomy: long-term followup using a new technique.
AB  - PURPOSE: We describe a new technique using a single ureteroscope and fluoroscopy
      for reestablishing ureteral continuity. MATERIALS AND METHODS: Nine patients with
      obliterated ureteral segments (1 bilateral) were referred for treatment, of whom
      3 had concurrent ureterovaginal fistulas. Mechanism of injury included open
      pelvic surgery in 9 ureteral segments and ureteroscopy in 1. Ureteral continuity
      was reestablished using a technique combining ureteroscopy and a fluoroscopically
      guided antegrade snare. The affected ureteral segment was then dilated and
      stented using a 14/7 reversed endopyelotomy stent. RESULTS: Ureteral continuity
      was reestablished in all 10 consecutive attempts with this technique. At a mean
      followup of 16 months (range 6 to 33) all patients were stent-free without
      radiological evidence of obstruction. All 3 patients with fistulas were dry. In 3
      patients ureteral strictures developed and required balloon dilation. Balloon
      dilation failed in 1 case and ultimately ureteral reimplantation was required.
      CONCLUSIONS: Ureteral continuity can be safely and effectively reestablished
      using a single ureteroscope. As a minimally invasive technique, endoscopic
      ureteroureterostomy should be considered before open surgical reconstruction.

PMID- 10893579
TI  - Endoscopic subureteral glutaraldehyde cross-linked collagen injection for the
      treatment of secondary vesicoureteral reflux: comparison with primary
      vesicoureteral reflux in adults.
AB  - PURPOSE: We assessed the effectiveness of endoscopic subureteral glutaraldehyde
      cross-linked collagen injection for treating vesicoureteral reflux in patients
      with vesicoureteral disorders. MATERIALS AND METHODS: All 51 ureters studied had
      grade II or greater vesicoureteral reflux. We treated 18 patients (24 refluxing
      ureters) with secondary and 17 adults (27 refluxing ureters) with primary
      vesicoureteral reflux. The primary group served as controls to establish normal
      urination. A total of 14 patients with secondary vesicoureteral reflux had a low
      compliant autonomous bladder, including 11 with myelodysplasia and 3 after pelvic
      surgery and radiotherapy. One patient had an unstable bladder due to cerebral
      palsy and 3 had anatomical abnormalities of the urinary tract. We evaluated the
      estimated reflux-free rate in the secondary and adult primary vesicoureteral
      reflux groups. RESULTS: Repeat injection was required in 24 ureters because of
      recurrent reflux. Average injected volume in the secondary and primary groups was
      2.72 and 2.88 ml. per refluxing unit, respectively. The estimated reflux-free
      rate after the initial injection decreased gradually to about 35% in each group,
      while 12 and 24 months after the last injection it remained constant at 70% in
      the secondary group but decreased from 84.7% to 62.1% in the primary group. The
      percent of late recurrence was higher in the primary group. CONCLUSIONS: Long
      term efficacy of the endoscopic correction of vesicoureteral reflux in the
      secondary group was similar to that in the primary group. Thus, endoscopic
      subureteral glutaraldehyde cross-linked collagen injection is useful for treating
      complicated secondary vesicoureteral reflux as a minimally invasive procedure. It
      is considered optional treatment of primary vesicoureteral reflux to avoid long
      term prophylactic treatment.

PMID- 10893580
TI  - Diagnostic value of intravesical lidocaine for overactive bladder.
AB  - PURPOSE: To determine the diagnostic use of intravesical lidocaine, we evaluated
      its effects on the overactive bladder in patients with brain lesions, spinal
      lesions, benign prostatic hyperplasia (BPH) and idiopathic overactive bladder.
      MATERIALS AND METHODS: Cystometry was performed before and 15 minutes after
      intravesical instillation of 20 ml. 4% lidocaine in 57 patients with an
      overactive detrusor in the storage phase. RESULTS: The percentage increase in
      bladder capacity for patients with spinal lesions was 136%, compared to 56%, 29%
      and 41% for patients with brain lesions, BPH and idiopathic bladder overactivity,
      respectively (significant difference p <0.01 to 0.05). Of the patients with an
      increase of 50% or more 55% had brain lesions, 80% spinal lesions, 23% BPH and
      31% idiopathic bladder overactivity. The incidence of the disappearance of
      detrusor contractions in patients with spinal lesions was greater than that in
      the others. CONCLUSIONS: These results suggest that intravesical instillation of
      4% lidocaine is useful for identification of overactive bladder attributable to
      spinal or other lesions.

PMID- 10893581
TI  - Combination of symptom score, flow rate and prostate volume for predicting
      bladder outflow obstruction in men with lower urinary tract symptoms.
AB  - PURPOSE: The severity of lower urinary tract symptoms associated with benign
      prostatic enlargement correlates poorly with bladder outlet obstruction. Since
      urodynamic studies are presumed to be relatively complex, invasive and not cost
      effective, they are not routinely performed by physicians treating men with lower
      urinary tract symptoms. As a result, a large number of patients are treated for
      bladder outlet obstruction when in fact obstruction may not be present. Since
      other noninvasive methods have not been effective for predicting bladder outlet
      obstruction, we investigated whether a combination of prostate volume,
      uroflowmetry and the American Urological Association (AUA) symptom index would be
      reliable for predicting this condition. MATERIALS AND METHODS: We prospectively
      evaluated 204 men with a mean age plus or minus standard deviation of 66.7 +/-
      7.5 years who presented with lower urinary tract symptoms. Each patient completed
      an AUA symptom index questionnaire and underwent uroflowmetry, post-void residual
      urine volume measurement, pressure flow study and transrectal ultrasound of the
      prostate to estimate prostatic volume. We constructed receiver operating
      characteristics curves using various threshold values for maximum urine flow and
      prostate volume. Threshold values for maximum urine flow and prostate volume were
      used alone and combined with the AUA symptom index for predicting bladder outlet
      obstruction. We selected a cutoff value for maximum urine flow of 10 or less ml.
      per second and prostate volume of 40 gm. or greater, and used these values with
      an AUA symptom index of greater than 20 to predict bladder outlet obstruction in
      the group overall. RESULTS: Differences in the mean symptom index score in men
      with and without bladder outlet obstruction were not statistically significant.
      There was no obstruction in 19%, 28.9% and 35% of those with severe, moderate and
      mild symptoms, respectively. The selected cutoff values of maximum urine flow,
      prostate volume and symptom score combined correctly predicted obstruction in all
      39 patients. Therefore, our combination of cutoff values proved to be highly
      accurate for predicting bladder outlet obstruction. Sensitivity, specificity, and
      positive and negative predictive values were 26%, 100%, 100% and 32%,
      respectively. CONCLUSIONS: Our study showed that combining the AUA symptom index,
      maximum urine flow and prostate volume reliably predicted bladder outlet
      obstruction in a small subset of patients only. Although bladder outlet
      obstruction was correctly predicted by our threshold values of AUA symptom index,
      maximum urine flow and prostate volume in only 39 men (26%) with obstruction,
      these patients represent a substantial group in any large urological practice
      treating male lower urinary tract symptoms.

PMID- 10893582
TI  - Fluorescence detection of flat bladder carcinoma in situ after intravesical
      instillation of hypericin.
AB  - PURPOSE: We determined the sensitivity and specificity of detecting flat bladder
      carcinoma in situ through fluorescent detection after intravesical hypericin
      instillations. MATERIALS AND METHODS: The study included 40 patients, of whom 26
      presented with macroscopic visible tumor, 9 had a positive cytology without
      visible tumor and 5 underwent cystoscopy after bacillus Calmette-Guerin
      instillations (4) or radiotherapy (1). We instilled 40 ml. of a 8 microM.
      solution of hypericin intravesically for at least 2 hours. Fluorescence
      excitation with blue light was effective up to 16 hours after termination of the
      instillation. RESULTS: All visible papillary tumors showed red fluorescence. In
      addition, 134 flat fluorescent areas were detected. Analysis of 281 biopsies from
      flat bladder wall indicated 93% sensitivity and 98.5% specificity for detecting
      carcinoma in situ. Visible lesions resulting from radiotherapy, chemotherapy or
      immunotherapy did not show any fluorescent signs and, therefore, did not induce
      false-positive readings. There were no signs of photobleaching during inspection
      and resection. CONCLUSIONS: We report a simple yet comprehensive endoscopic
      method for early detection of bladder cancer, including carcinoma in situ.
      Hypericin induced fluorescence has a high sensitivity and specificity for
      detection of bladder transitional cell carcinoma, papillary and flat carcinoma in
      situ. When carcinoma in situ is suspected, this technique is highly recommended.

PMID- 10893583
TI  - The role of volume weighted mean nuclear volume in predicting the prognosis of
      patients with primary transitional cell carcinoma of the upper urinary tract: a
      report of 102 new cases.
AB  - PURPOSE: We compare estimates of volume weighted mean nuclear volume (MNV) with
      histological grading to determine the prognosis of primary transitional cell
      carcinoma of the upper urinary tract using a Cox proportional hazards model.
      MATERIALS AND METHODS: We retrospectively reviewed 102 patients who underwent
      nephroureterectomy for primary transitional cell carcinoma of the upper urinary
      tract at our hospital between April 1981 and March 1997. Traditional prognostic
      factors, such as patient age, sex, stage and grade, multiplicity and unbiased
      estimates of MNV were analyzed with respect to disease recurrence and survival.
      RESULTS: Estimates of mean nuclear volume were significantly larger for patients
      with than without lymph node metastasis (p = 0.0031). No prognostic factor
      significantly correlated with recurrence of transitional cell carcinoma of the
      bladder. For pTxN0M0 cases univariate analysis revealed that histological grade
      (p = 0.0018), pathological T stage (p = 0.0030) and estimates of MNV (p = 0.0001)
      correlated significantly with disease specific survival, and multivariate
      stepwise regression analysis revealed that estimate of MNV was the only powerful
      predictor of prognosis (p = 0.0007). CONCLUSIONS: Our results indicate that
      estimate of MNV is an important predictor of prognosis for transitional cell
      carcinoma of the upper urinary tract. We recommend MNV estimate as a supportive
      method for subjective histological grading.

PMID- 10893584
TI  - Urodynamic evaluation and long-term results of the orthotopic gastric neobladder
      in men.
AB  - PURPOSE: Orthotopic neobladders are most commonly formed from colon and/or small
      bowel segments. However, after excellent results were reported in children, we
      constructed gastric neobladders in select men who had undergone cystectomy.
      Although gastric neobladders in adults have been reported to have decreased
      capacity, to our knowledge neither long-term followup nor urodynamic parameters
      have been reported in these patients. MATERIALS AND METHODS: Gastric neobladder
      was performed in 8 patients following cystectomy for malignancy in 7 and
      undiversion in 1. Average followup was 43 months and all patients underwent
      urodynamic evaluations an average of 9.1 months after surgery. Patients also
      completed an incontinence questionnaire. The gastric neobladder group was
      compared to a similar group of patients who underwent neobladder construction
      from either small bowel (Kock/Hautmann/Studer) or ileocecal segments (Mainz).
      RESULTS: The gastric neobladder group had significantly reduced mean bladder
      capacity compared to the ileal or ileocecal neobladder group (309 versus 551 cc,
      respectively, t = 0.001), while compliance was similarly decreased (27 versus 59
      cc/cm. H2O, respectively, t = 0.04). Incontinence rates were greater in the
      gastric neobladder group (63%) compared to the ileal or ileocecal neobladder
      group (8% to 23%, t = 0.02). Complication rates were comparable. Revision or
      removal was required in 3 (38%) patients for severe incontinence, intractable
      dysuria and ureterogastric anastomotic stricture, respectively. CONCLUSIONS:
      Adult gastric neobladders as currently constructed are associated with poor
      urodynamic parameters and high incontinence rates. Routine use of gastric
      neobladders in adults is not recommended. They may be appropriate, especially as
      composites, in select cases such as renal failure or inadequate bowel length. The
      reasons for success in some patients and not in others are unknown.

PMID- 10893585
TI  - Complications related to the high lithotomy position during urethral
      reconstruction.
AB  - PURPOSE: We identified risk factors for complications of the lower extremities
      related to high lithotomy positioning during specific urethral reconstruction
      procedures in male patients. MATERIALS AND METHODS: Records from 185 open
      urethroplasties were evaluated for position related complications of the lower
      extremities (the compartmental syndrome, rhabdomyolysis, neurapraxia).
      Morphometric data (patient height, weight) and surgical details (duration of
      surgery and lithotomy positioning, types of repair and stirrups, stricture length
      and location) were assessed. RESULTS: In the 185 patients 18 position related
      complications (10%) were identified, 4 of which were severe. Univariate analysis
      showed length of stricture, and duration of surgery and lithotomy positioning to
      be statistically significant risk factors (p <0.05). Height, weight, body mass
      index and type of stirrups did not increase risk. Anterior end-to-end anastomosis
      and straightforward buccal mucosa patch grafts entailed negligible risk. Longer
      procedures (prostatomembranous and penile skin flap repairs) had higher
      complication rates (12% and 22%, respectively). Beginning penile skin flap
      procedures with patients in the supine position during flap harvesting followed
      by repositioning into high lithotomy for perineal flap transfer virtually
      eliminated the risk of severe complications. CONCLUSIONS: The risk of position
      related complications during urethral reconstruction is directly proportional to
      the duration of high lithotomy positioning. Procedures of less than 5 hours in
      duration had minimal risk. For complex flap procedures, we perform penile flap
      dissection with the patient supine and reposition for perineal flap transfer.

PMID- 10893586
TI  - Penile fracture in Kermanshah, Iran: report of 172 cases.
AB  - PURPOSE: Experience with 172 cases of penile fracture, in Kermanshah, Iran is
      reviewed. MATERIALS AND METHODS: Records of penile fracture cases were reviewed
      from April 1990 to October 1999. RESULTS: Diagnosis was made clinically and there
      was no need to perform cavernosography in any case. The most common mechanism of
      fracture was referred to by patients as "taghaandan" (to click or snap when
      forcibly pushing the erect penis down to achieve detumescence). All but 2 cases
      were treated surgically and 2 cases had concomitant urethral injury diagnosed by
      selective urethrography. Repair consisted of a circumferential degloving incision
      to evaluate the corpora. Because of unavailability of synthetic absorbables,
      inverted knot nylon sutures were used successfully for repair. Delay in operation
      did not increase difficulty in dissection or early postoperative morbidity.
      Preoperative and postoperative use of antibiotics was effective in eliminating
      risk of infection. There were no significant intraoperative or immediate
      postoperative complications and most patients were discharged home on
      postoperative day 1. CONCLUSIONS: Patient misinformation about penile tissue
      properties is the main explanation for the high incidence of penile fracture.
      Cavernosography, and urethrography and intraoperative urethral catheterization
      are not routinely needed, as diagnosis can be made clinically. Preoperative and
      postoperative use of antibiotics, and a uniform surgical plan regardless of delay
      in presentation are recommended.

PMID- 10893587
TI  - Effect of erectile dysfunction on frequency of intercourse: a population based
      prevalence study in Finland.
AB  - PURPOSE: We estimate the prevalence of erectile dysfunction in Finland and its
      effect on frequency of sexual intercourse. MATERIALS AND METHODS: A population
      based study of 3,143, 50, 60 and 70-year-old men in Tampere and 11 municipalities
      in the same county was conducted by mailed questionnaire. The definition of
      erectile dysfunction was based on difficulties in achieving an erection before
      sexual intercourse and maintaining it. Erectile dysfunction was classified into 4
      groups as none, minimal, moderate and complete. To estimate the effect of
      erectile dysfunction on the frequency of sexual intercourse the men were divided
      into those who had intercourse at least an average of once weekly and those who
      did not. RESULTS: A total of 2,198 questionnaires (70%) were returned and 1, 983
      men (63%) were included in the study. Of these men 26% had no, 48% minimal, 14%
      and 12% complete erectile dysfunction, which increased with age (compared with 50
      year-old men, the odds ratios for complete erectile dysfunction were 4.5 (95%
      confidence interval [CI] 2.6-7.5) for 60 and 21 (95% CI 12.5 to 34.7) to 70-year
      old men. The effect of erectile dysfunction on the frequency of sexual
      intercourse could not be accounted for by age or marital status. The adjusted
      effect was strong among men with moderate (odds ratio 3.5, 95% CI 2.2-5.1) and
      complete (173, 68-443) erectile dysfunction but minimal erectile dysfunction had
      no impact (odds ratio 0.9, 95% CI 0. 6-1.3) on the frequency of intercourse.
      CONCLUSIONS: Erectile difficulties are common and complete erectile dysfunction
      increases with age. Erectile dysfunction regulates the sex life of men with
      moderate or complete dysfunction but this association cannot be accounted for by
      age or marital status. Although mild erectile dysfunction did not completely
      regulate sex life, its significance is the risk of progression to a more severe
      sexual life disturbing dysfunction.

PMID- 10893588
TI  - Testosterone supplementation for erectile dysfunction: results of a meta
      analysis.
AB  - PURPOSE: To our knowledge a causal relationship between altered levels of
      androgens and erectile dysfunction has not yet been established. We reviewed the
      literature to assess the usefulness of androgen replacement for erectile
      dysfunction. MATERIALS AND METHODS: Meta-analysis was chosen as the method of
      evaluating the literature. Study inclusion criteria were testosterone given as
      the only therapy for erectile dysfunction and a clearly stated definition of
      response for evaluating treatment success or failure. RESULTS: We evaluated 73
      articles obtained by a MEDLINE search of 1966 to 1998 and included 16 in our
      study. The overall response rate was 57%. In the 9 series with response rate by
      etiology patients with primary versus secondary testicular failure had a response
      rate of 64% versus 44% (p <0.001). Intramuscular and oral methods of delivery
      were equivalent with a response rate of 51.3% and 53.2%, respectively. However,
      the response to transdermal therapy was significantly different from that of
      intramuscular and oral treatment (80.9% versus 51.3% and 53.2%, respectively, p
      <0.001). The mean confidence level response for testosterone treatment was 16. 7%
      in the placebo and 65.4% in the treated group (p <0.0001). CONCLUSIONS: Our meta
      analysis of the usefulness of androgen replacement therapy for erectile
      dysfunction indicates that the response rate for a primary etiology was improved
      over that for a secondary etiology, transdermal testosterone therapy was more
      effective than intramuscular or oral treatment, and intramuscular and oral
      treatments were equivalent. In addition, there was a statistically significant
      difference in favor of testosterone over placebo, implying a role for
      supplementation in select groups.

PMID- 10893589
TI  - Efficacy, safety and patient satisfaction outcomes of the AMS 700CX inflatable
      penile prosthesis: results of a long-term multicenter study. AMS 700CX Study
      Group.
AB  - PURPOSE: We performed a long-term multicenter study of the AMS 700CX 3-piece
      inflatable penile prosthesis, focusing on longevity, morbidity and patient
      satisfaction in men implanted up to 134 months with a median followup of 47.7
      months. MATERIALS AND METHODS: We performed a large scale retrospective
      multicenter study in 2 phases. Phase 1 was a medical record review of 372 men who
      underwent implantation with the AMS 700CX penile prosthesis from 1987 to 1996 by
      7 frequent penile prosthesis implanters. Phase 2 included a structured telephone
      interview of 207 patients by a neutral observer. RESULTS: For the 372 men in
      phase 1 mean device mechanical reliability plus or minus standard deviation was
      92.1% + or - 3.3% after 3 and 86.2% + or - 4.6% after 5 years. Patient age was 21
      to 79 years (mean 57.6 + or - 11.0) at implantation. The etiology of erectile
      dysfunction was vascular in 27.7% of the cases, Peyronie's disease in 16.9%,
      diabetes mellitus in 12.9% and radical surgery in 11.6%. Of the men 55.6%
      received previous treatment for erectile dysfunction. Postoperative infection and
      device malfunction developed in 3.2% and 17.5% of the cases, respectively. Of the
      207 men interviewed in phase 2, 86% still had an AMS 700CX penile prosthesis
      implanted, including 87.1% with erection suitable for coitus. Currently 79% of
      those with a device use it at least twice monthly and 88.2% would recommend an
      implant to a relative or friend. CONCLUSIONS: The AMS 700CX penile implant
      produced suitable erection and excellent patient satisfaction at long-term
      followup in the majority of men. Implant reliability is excellent and
      postoperative morbidity is low.

PMID- 10893590
TI  - Salvage surgery of chemorefractory germ cell tumors with elevated tumor markers.
AB  - PURPOSE: We evaluated the prognostic criteria for salvage surgery in patients
      with persistent marker elevation after chemotherapy for metastatic germ cell
      tumors. MATERIALS AND METHODS: Of 125 men who underwent post-chemotherapeutic
      resection of residual tumors 30 had persistent marker elevation at surgery. This
      group was subdivided into 17 patients with no evidence of disease, 7 dead of
      disease and 6 others. Outcome analysis was performed in the subgroups with regard
      to preoperative and postoperative parameters. Mean followup was 120.3 months
      (range 1 to 228) after surgery. RESULTS: Of the 30 patients 17 (57%) with
      persistently elevated tumor markers after chemotherapy were long-term survivors
      after salvage surgery. Overall persistent viable cancer and teratomatous elements
      were identified in 64% and 11% of cases, respectively. Significantly more
      patients died of disease who had a poor prognosis according to International Germ
      Cell Cancer Collaborative Group guidelines. Embryonal carcinoma was the
      predominant initial histology in this group and residual disease was more often
      located at various sites, for example the viscera, with a lower chance of
      complete surgical resection. Marker status before surgery, and chemotherapeutic
      pretreatment and postoperative histological findings did not differ significantly
      in patients with no evidence of disease and those dead of disease. CONCLUSIONS:
      Salvage surgery results in long-term success in greater than 50% of patients.
      Complete resection is the most important single parameter for a favorable
      outcome. Even patients with visceral metastasis benefit from surgery. Our data do
      not justify omitting surgery in certain subgroups.

PMID- 10893591
TI  - Transperineal magnetic resonance image guided prostate biopsy.
AB  - PURPOSE: We report the findings of a transperineal magnetic resonance image (MRI)
      guided biopsy of the prostate in a man with increasing prostate specific antigen
      who was not a candidate for a transrectal ultrasound guided biopsy. MATERIALS AND
      METHODS: Using an open configuration 0.5 Tesla MRI scanner and pelvic coil, a
      random sextant sample was obtained under real time MRI guidance from the
      peripheral zone of the prostate gland as well as a single core from each MRI
      defined lesion. The patient had previously undergone proctocolectomy for
      ulcerative colitis and, therefore, was not a candidate for transrectal ultrasound
      guided biopsy. Prior attempts to make the diagnosis of prostate cancer using a
      transurethral approach were unsuccessful. RESULTS: The random sextant samples
      contained benign prostatic hyperplasia, whereas Gleason grade 3 + 3 = 6
      adenocarcinoma was confirmed in 15% and 25% of the 2 cores obtained from the MRI
      targeted specimens of 2 defined lesions. The procedure was well tolerated by the
      patient. CONCLUSIONS: Transperineal MRI guided biopsy is a new technique that may
      be useful in detecting prostate cancer in men with increasing prostate specific
      antigen who are not candidates for transrectal ultrasound guided biopsy.

PMID- 10893592
TI  - A prospective randomized trial comparing 6 versus 12 prostate biopsy cores:
      impact on cancer detection.
AB  - PURPOSE: Several studies suggest that sextant transrectal ultrasound guided
      biopsy of the prostate provides insufficient material to detect all clinically
      important prostate cancer, and obtaining more biopsy cores may improve the cancer
      detection rate. We performed a prospective randomized trial comparing 6 to 12
      prostate biopsy cores to determine the impact on the cancer detection rate.
      MATERIALS AND METHODS: We prospectively randomized 244 men, including 71 (29%)
      black men, with a mean age plus or minus standard deviation of 65 +/- 8 years to
      undergo biopsy with 6 or 12 peripheral zone tissue cores. In our study subjects
      serum total prostate specific antigen (PSA) was between 2.5 and 20 ng./ml.,
      and/or digital rectal examination was suspicious for cancer. All men completed a
      self-administered pre-biopsy and 2 post-biopsy questionnaires at 2 and 4 weeks.
      Cancer detection rates were compared in the groups and correlated with race,
      biopsy history, digital rectal examination findings, total PSA, transrectal
      ultrasound volume and PSA density, as determined by the formula, total
      PSA/transrectal ultrasound volume. RESULTS: The cancer detection rate in the 6
      and 12 core groups was almost identical (26% and 27%, p = 0.9). There was no
      significant difference in cancer detection in the 2 trial arms with respect to
      subject race, biopsy history, digital rectal examination findings, total PSA,
      transrectal ultrasound volume or PSA density. However, our study did not have the
      statistical power to rule out small differences. CONCLUSIONS: The overall cancer
      detection rate is not materially increased by 12 core, peripheral zone biopsy in
      men in whom prostate cancer was mainly detected by screening.

PMID- 10893593
TI  - Extensive biopsy protocol improves the detection rate of prostate cancer.
AB  - PURPOSE: We evaluated improvement in the rate of prostate cancer detection when
      using an extensive biopsy protocol involving peripheral cores. MATERIALS AND
      METHODS: We prospectively evaluated 303 consecutive men who underwent transrectal
      ultrasound guided biopsy due to elevated prostate specific antigen (PSA) and/or
      abnormal digital rectal examination. Ten biopsies were performed, including at
      least 5 at the base and middle of each lobe. In addition to standard biopsy at a
      45-degree angle, a more peripheral 30-degree angle biopsy was obtained. At the
      apex only 1 standard biopsy was done. However, when prostate volume was greater
      than 50 cm.3, an additional peripheral biopsy was obtained at the apex. RESULTS:
      The complication rate in this biopsy protocol was 1% (3 patients). Prostate
      cancer was detected in 118 of the 303 men (38. 9%). Overall this extensive
      protocol resulted in 6.6% improvement in the detection rate. Improvement was 6.5%
      in men with PSA 10 ng./ml. or less and 7% in those with PSA greater than 10 (not
      significant). CONCLUSIONS: Increasing the number of biopsy cores and improving
      prostate peripheral zone sampling resulted in a significant improvement in the
      detection of prostate cancer.

PMID- 10893594
TI  - A randomized prospective trial of intrarectal lidocaine for pain control during
      transrectal prostate biopsy: the Emory University experience.
AB  - PURPOSE: We prospectively evaluated the safety and efficacy of intrarectal
      lidocaine gel as anesthesia during transrectal prostate biopsy. MATERIALS AND
      METHODS: Of 63 consecutive men undergoing transrectal prostate biopsy 50 who
      qualified were enrolled in this study. Indications for the procedure were an
      abnormal prostate on digital rectal examination and/or elevated serum prostate
      specific antigen. Patients were randomized into group 1-25 who received 10 cc of
      2% intrarectal lidocaine 10 minutes before the procedure and group 2-25 controls.
      No narcotics, sedation or analgesia was given. Pain during biopsy was assessed
      using a 10-point linear visual analog pain scale. RESULTS: In groups 1 and 2
      median patient age was 63 and 66 years (p = 0.139), and median prostate specific
      antigen was 6.04 (range 1.07 to 263) and 7.24 (range 1.34 to 51.82) ng./ml. (p =
      0.337). Digital rectal examination was normal and abnormal in 17 and 15 group 1,
      and in 8 and 10 group 2 patients, respectively. Ultrasound showed a median
      prostate volume of 43.6 cc (range 15.3 to 124) in group 1 and 40.3 (range 19.8 to
      132) in group 2 (p = 0.710). Final histological results revealed prostate cancer
      in 7 men (28%) in each group. The median pain score during transrectal prostate
      biopsy was 2 (range 1 to 5) and 5 (range 1 to 7) in groups 1 and 2, respectively
      (p = 0.00001). No adverse events were noted. CONCLUSIONS: Intrarectal lidocaine
      gel is a simple, safe and efficacious method of providing satisfactory anesthesia
      in men undergoing transrectal prostate biopsy. We recommend its routine
      administration in all patients during this procedure.

PMID- 10893596
TI  - Editorial: improving prostate cancer detection

PMID- 10893595
TI  - Sextant localization of prostate cancer: comparison of sextant biopsy, magnetic
      resonance imaging and magnetic resonance spectroscopic imaging with step section
      histology.
AB  - PURPOSE: We compared the accuracy of endorectal magnetic resonance imaging (MRI)
      and magnetic resonance spectroscopic imaging with that of sextant biopsy for the
      sextant localization of prostate cancer. MATERIALS AND METHODS: Sextant biopsy,
      MRI, magnetic resonance spectroscopic imaging and radical prostatectomy with step
      section histology were done in 47 patients with prostate cancer. For each sextant
      we categorized biopsy and imaging results as positive or negative for cancer.
      Step section histology was used as the standard of reference. RESULTS: For
      sextant localization of prostate cancer MRI and magnetic resonance spectroscopic
      imaging were more sensitive but less specific than biopsy (67% and 76% versus
      50%, and 69% and 68% versus 82%, respectively). The sensitivity of sextant biopsy
      was significantly less in the prostate apex than in the mid prostate or prostate
      base (38% versus 52% and 62%, respectively). MRI and magnetic resonance
      spectroscopic imaging had similar efficacy throughout the prostate compared with
      biopsy only as well as better sensitivity and specificity in the prostate apex
      (60% and 75%, and 86% and 68%, respectively). A positive biopsy or imaging result
      had 94% sensitivity for cancer and concordant positivity by all 3 tests was
      highly specific at 98%. CONCLUSIONS: Overall MRI and magnetic resonance
      spectroscopic imaging have accuracy similar to biopsy for intraprostatic
      localization of cancer and they are more accurate than biopsy in the prostate
      apex. These 2 imaging modalities may supplement biopsy results by increasing
      physician confidence when evaluating intraprostatic tumor location, which may be
      important for planning disease targeted therapy.

PMID- 10893597
TI  - Improvement of transperineal implant dosimetry by intraoperative cystoscopic
      confirmation of prostate anatomy.
AB  - PURPOSE: A simple, inexpensive method to aid in the accurate placement of
      permanent seeds for prostate brachytherapy is described. The effect of
      identifying the prostate base and apex cystoscopically relative to registration
      seeds placed at the beginning of the implant is discussed. MATERIALS AND METHODS:
      At the beginning of each implant procedure a pair of marker seeds are first
      placed in the prostate, including 1 seed at the base and 1 at the apex. Using a
      cystoscope, the urologist identifies the prostatic base and apex, and a
      fluoroscopic record is obtained. The positions of the base and apex relative to
      the marker seeds are monitored throughout the case via fluoroscopy to aid in
      needle and seed placement for the implant. RESULTS: Use of this method
      significantly improved coverage of the prostate apex, reduced overall dose
      variance in the prostate base and improved overall gland dosimetry by 22% as
      measured by the D90 quality metric (minimal dose which covers 90% of the prostate
      volume). CONCLUSIONS: While the clinical efficacy of improved target coverage on
      local control and survival awaits further clinical investigation, we encourage
      others to adopt this easy technique to ensure better, more consistent
      interstitial implants.

PMID- 10893598
TI  - Histopathological prostate cancer characteristics at radical prostatectomy after
      population based screening.
AB  - PURPOSE: Although early detection of prostate cancer by prostate specific antigen
      based screening results in a shift towards more clinically organ confined tumors,
      changes in prostate cancer characteristics after radical prostatectomy are less
      clear. MATERIALS AND METHODS: We studied 121 totally embedded radical
      prostatectomy specimens that were obtained from consecutive participants of the
      European Randomized Study of Screening for Prostate Cancer who were
      systematically screened and treated surgically. In each specimen pathological
      stage, Gleason score and proportion of high grade cancer (Gleason pattern 4 or 5)
      were determined. Lymph node status at operation, stage and grade were compared to
      a historical series of 72 surgical procedures performed for clinically localized
      prostate cancer at our hospital before the introduction of serum prostate
      specific antigen as a diagnostic tool. RESULTS: Although none of the screen
      detected cases had positive lymph nodes at surgery, operation was discontinued in
      13 (18%) of the 72 historical cases because of positive lymph nodes. Compared
      with the remaining 59 historical prostatectomy specimens, the screen detected
      specimens showed a definite increase in the frequency of pathologically organ
      confined tumors and a relative decrease in Gleason score 8 to 10 tumors. However,
      60% of screen detected tumors contained areas with high grade cancer (Gleason
      pattern 4 or 5) and 50% had a Gleason score of 7. The relative amount of high
      grade cancer in each tumor was related to volume (Kruskal-Wallis test p <0. 001).
      CONCLUSIONS: Screening for prostate cancer leads to an increase in surgical
      treatment for relatively small tumors that have a higher probability of being
      organ confined. Although the frequency of positive lymph nodes at operation
      decreases dramatically and the proportion of organ confined tumors after surgery
      increases, there is a shift from Gleason 8 to 10 tumors towards lower grade
      tumors at radical prostatectomy. Still, judged by the high frequency of focal
      dedifferentiation in screen detected tumors, most of them and surgically treated
      tumors are likely to be clinically important. The relatively large accumulation
      of these tumors in the Gleason 7 category is a concern because it could lead to a
      decrease in the clinical usefulness of the Gleason score system.

PMID- 10893599
TI  - Exposure of the anterior spine: technique and experience with 66 patients.
AB  - PURPOSE: Anterior spinal fusion has become an increasingly popular technique used
      by orthopedic surgeons for a variety of lower spine pathology. At our institution
      urologists have assisted as retroperitoneal surgeons in achieving exposure of the
      appropriate spinal disk space. We report our experience with anterior spinal
      fusion in 66 patients. MATERIALS AND METHODS: Since 1991 we have performed 66
      exposures using the flank, modified Gibson, thoracoabdominal, paramedian and
      midline transperitoneal approaches. Exposure of each level has subtle technical
      issues which are reviewed. RESULTS: During the study 34 men and 32 women 24 to 74
      years old (mean age 43.8) underwent discectomy and anterior fusion of the spine.
      Access from T12 through L5-S1 interspace was required, and exposure of multiple
      spinal levels was necessary in 27. There was 1 death from massive pulmonary
      embolism in a patient with widely metastatic lung cancer. Retrograde ejaculation
      was reported by 2 men. There have been no episodes of deep or superficial wound
      infection and no ureteral or major vascular injuries. CONCLUSIONS: As surgeons of
      the retroperitoneum urologists have an important role in providing our orthopedic
      colleagues with safe, adequate exposure to the anterior surface of the spine
      during discectomy and anterior fusion.

PMID- 10893600
TI  - A new direct test of bladder permeability.
AB  - PURPOSE: A proposed cause of interstitial cystitis is increased bladder
      permeability but to our knowledge this theory has not been proved by direct
      testing. We developed a safe, relatively painless, direct test of bladder
      permeability. MATERIALS AND METHODS: The original permeability test involved
      placing 4% lactulose and 1% rhamnose intravesically, then drawing blood to assay
      for these sugars. Initial feasibility studies were performed in rabbits with
      bladder epithelium that was intact or disrupted by a 50% acetone rinse. In humans
      the initial goal was to distinguish intact bladders from those known to have
      increased permeability. Since distention is known to increase permeability
      temporarily, we studied patients with interstitial cystitis immediately after
      distention. RESULTS: Neither sugar was absorbed from intact rabbit bladders,
      while each was absorbed from acetone rinsed bladders at 10, 20 and 30 minutes. We
      used 100 ml. of solution in the initial 8 humans, including 6 with interstitial
      cystitis and 2 controls. At 30 minutes each sugar was absorbed from interstitial
      cystitis bladders but neither was absorbed from intact bladders. The test
      solution was then changed to 5% rhamnose. Mean rhamnose absorption plus or minus
      standard deviation was much greater in the 6 patients with interstitial cystitis
      than in 8 controls (26.3 + or - 26.1 versus 0.78 + or - 0.87 nmol. /ml. serum, p
      = 0.008). With 1 exception interstitial cystitis serum levels were at least 4
      fold higher than the highest control level. CONCLUSIONS: This new permeability
      test clearly distinguishes intact versus distended bladders. It may be performed
      to test whether bladder permeability is increased in interstitial cystitis.

PMID- 10893602
TI  - Urethral diverticulum in women: diverse presentations resulting in diagnostic
      delay and mismanagement.
AB  - PURPOSE: We describe various clinical presentations of urethral diverticulum,
      which may mimic other pelvic floor disorders and result in diagnostic delay.
      Management and outcome results are reported. MATERIALS AND METHODS: We reviewed
      retrospectively 46 consecutive cases of urethral diverticulum. Patient
      characteristics, history, clinical evaluation, management and long-term followup
      are reported. RESULTS: Mean patient age plus or minus standard deviation was 36.3
      +/- 11.7 years. Most (83%) cases were referred as diagnostic dilemmas with
      symptoms present for 3 months to 27 years. Mean interval between onset of
      symptoms to diagnosis was 5.2 years. The most common symptoms were pain (48% of
      cases), urinary incontinence (35%), dyspareunia (24%) and frequency/urgency
      (22%). The number of physicians previously consulted ranged from 3 to 20 and
      prior therapies included oral and/or vaginal medications, anti-incontinence
      surgery and psychotherapy. The diverticulum was palpable on examination in 24
      patients (52%), in only 6 of whom was it possible to "milk" contents per meatus.
      Of these 24 palpable diverticula 2 contained malignancy, and 2 others contained
      endometriosis and stones, respectively. Diagnosis was made by voiding
      cystourethrography in 30 cases (65%), double balloon urethrography in 5 (11%) and
      transvaginal ultrasound or magnetic resonance imaging in 7 (15%). Diverticula
      were incidental findings during vaginal surgery in 4 cases (9%). Treatment
      consisted of diverticulectomy and/or Martius flap, pubovaginal sling and urethral
      reconstructive procedures when indicated in 35 cases (76%), and 2 other patients
      underwent radical surgery for diverticular malignancy. Subsequently all but 2
      patients with pain were cured. In another patient de novo stress incontinence
      developed postoperatively. None of the patients who underwent concomitant
      pubovaginal sling had postoperative incontinence. CONCLUSIONS: The symptoms of
      urethral diverticulum may mimic other disorders. This condition should be
      considered in women with pelvic pain, urinary incontinence and irritative voiding
      symptoms not responding to therapy. Surgical treatment is usually effective in
      alleviating associated symptoms.

PMID- 10893601
TI  - Quality of life among women with interstitial cystitis.
AB  - PURPOSE: Clinical case series suggest that the impact of interstitial cystitis on
      quality of life is severe and debilitating, however, little epidemiologic
      information is available. We examined the impact of interstitial cystitis on
      quality of life in a population based cohort of United States women. MATERIALS
      AND METHODS: We collected multidimensional measures of quality of life from
      159,419 participants in the Nurses' Health Study I and II using a validated
      instrument, the Medical Outcome Study Short-Form 36 Health Survey Instrument.
      This instrument measures physical function, role limitations due to physical and
      emotional problems, bodily pain, vitality, social function and mental health.
      Quality of life measures were collected on 99 women with prevalent self reported
      interstitial cystitis confirmed by medical record review. RESULTS: After
      adjusting for age and co-morbid conditions, women with interstitial cystitis had
      significantly lower quality of life scores in 4 of the 7 quality of life
      dimensions, including role/physical (beta -13.1, p <0.001), bodily pain (beta 
      9.8, p <0.001), vitality (beta -7.7, p <0.001) and social function (beta -7.2, p
      <0.001) compared to women without interstitial cystitis. Women with interstitial
      cystitis experienced less decrement in physical function compared to women with
      rheumatoid arthritis but more compared to women with hypertension. In addition,
      they experienced greater differences in vitality and mental health than women
      with rheumatoid arthritis or hypertension. CONCLUSIONS: The quality of life among
      women with interstitial cystitis was especially limited in the psychosocial
      dimensions, such as vitality and mental health. Future research on interstitial
      cystitis should incorporate multidimensional measures of quality of life,
      especially with respect to response to the various treatments.

PMID- 10893603
TI  - Variations in strategy for the treatment of urethral obstruction after a
      pubovaginal sling procedure.
AB  - PURPOSE: We evaluated the success of several techniques for treating urethral
      obstruction and erosion after a pubovaginal sling procedure. MATERIALS AND
      METHODS: Between April 1998 and June 1999, 32 women 33 to 79 years old (average
      age 62) who underwent a pubovaginal sling procedure with various materials were
      referred for the assessment of urethral obstruction. Patients were evaluated with
      a urogynecologic history, physical examination, voiding diary, cystoscopy and
      video urodynamics. Surgical procedures to resolve urethral obstruction were
      performed transvaginally and the specific techniques used were based on the type
      of sling material, urethral erosion and concomitant stress incontinence or other
      urethral pathology. Outcome measures were assessed by disease specific quality of
      life questionnaires, voiding diary and urogynecologic questionnaire. RESULTS:
      Preoperatively 30 of the 32 women (93.7%) noticed urge incontinence, 20 (62.5%)
      performed intermittent self-catheterization, 6 (18.7%) had an indwelling catheter
      and 3 (9%) complained of concomitant stress urinary incontinence. After the sling
      takedown 29 patients (93.5%) achieved efficient voiding within week 1
      postoperatively. Urge incontinence symptoms resolved in 20 cases (67%) but stress
      incontinence developed in 3 (9%). Of the 32 women 27 (84%) indicated that
      continence was much better than before the initial sling procedure. CONCLUSIONS:
      Managing urethral obstruction after a pubovaginal sling procedure is challenging.
      Using various techniques based on sling material, urethral erosion and bladder
      neck integrity a successful outcome is possible in the majority of cases.

PMID- 10893604
TI  - Bilateral hydronephrosis from ciprofloxacin induced crystalluria and stone
      formation.

PMID- 10893605
TI  - Ileal conduit intestinal fistula presenting as acute renal failure.

PMID- 10893606
TI  - Intermittent anuria secondary to a stone in a ureterofemoral hernia.

PMID- 10893607
TI  - Perforation of sigmoid colon after extracorporeal lithotripsy.

PMID- 10893608
TI  - Recurrent intraluminal ureteral metastasis of a testicular seminoma.

PMID- 10893609
TI  - Diagnosis of retroperitoneal pulmonary sequestration using computerized
      tomography guided fine needle biopsy.

PMID- 10893610
TI  - Intravesical dimethyl sulfoxide instillations can be useful in the symptomatic
      treatment of profuse hematuria due to eosinophilic cystitis.

PMID- 10893611
TI  - Penile fracture of the proximal corporeal body.

PMID- 10893612
TI  - Partial penile disassembly and corporeal resection for Peyronie's disease with
      distal narrowing.

PMID- 10893613
TI  - Intratesticular self-injection of testgasoline.

PMID- 10893614
TI  - Malignant germ cell tumor of the contralateral testis after radiotherapy for
      testicular intraepithelial neoplasia.

PMID- 10893615
TI  - Treatment of large prostatic cyst with retropubic insertion of a fat tissue flap.

PMID- 10893616
TI  - Three-dimensional digital ultrasound for early staging of prostatic
      adenocarcinoma.

PMID- 10893617
TI  - Incidental finding of an isolated prostate cancer metastasis in an inguinal
      hernial sac.

PMID- 10893618
TI  - Use of pleural fluid prostate specific antigen in the diagnosis of malignant
      effusion from metastatic prostate cancer.

PMID- 10893619
TI  - Re: Incorporation of patient preferences in the treatment of upper urinary tract
      calculi: a decision analytical view.

PMID- 10893620
TI  - Re: Functional lower urinary tract voiding outcomes after cystectomy and
      orthotopic neobladder.

PMID- 10893621
TI  - Re: Monoclonal antibody confirmation of a primary leiomyoma of the testis.

PMID- 10893622
TI  - Re: Back to future-the role of complementary medicine in urology.

PMID- 10893623
TI  - Nephrolithiasis associated with the ketogenic diet.
AB  - PURPOSE: The ketogenic diet has been used for treating seizure disorders for more
      than 70 years. Nephrolithiasis is a known complication of this diet with a
      reported stone rate as high as 10% but there is sparse literature detailing the
      nature and treatment of these stones. We report on 4 children with
      nephrolithiasis on this diet. MATERIALS AND METHODS: We describe stone treatment
      and analysis as well as metabolic and urine abnormalities in 4 children with
      nephrolithiasis on the ketogenic diet who presented to our institution. RESULTS:
      All patients were treated with shock wave lithotripsy, fluid liberalization and
      oral citrate. One child was ultimately withdrawn from the diet due to persistent
      stone formation. Analysis revealed 3 calcium and 1 ammonium urate stones. Three
      patients had hypercalciuria, 2 elevated urinary uric acid and 1 hypocitruria.
      Serum studies revealed acidosis in 3 cases. CONCLUSIONS: The ketogenic diet
      induces several metabolic abnormalities that increase the propensity for stone
      formation. Urologists should be aware of this potential complication. Fluid
      liberalization and bicitrate are recommended as prophylaxis.

PMID- 10893624
TI  - Variability of diuresis renography interpretation due to method of post-diuretic
      renal pelvic clearance half-time determination.
AB  - PURPOSE: We assessed variability in the interpretation of diuresis renography
      that may result from using different methods of clearance half-time
      determination. MATERIALS AND METHODS: We reviewed 152 diuresis renography studies
      performed at diagnosis or during followup of 53 children enrolled in a
      prospective study assessing the natural history of unilateral neonatal
      hydronephrosis. Studies were classified as nonobstructive, indeterminate or
      obstructive using 4 methods of half-time determination. Intermethod correlation
      and agreement were evaluated. We compared the proportion of nonobstructive,
      indeterminate and obstructive classifications by each method, and the
      interpretation of individual studies based on each method. RESULTS: Among methods
      we noted a high degree of correlation and fair to excellent agreement (Spearman
      rho = 0.86 to 0.92 and kappa = 0.57 to 0.86, respectively). However, in 27.8% of
      intermethod comparisons the proportion of studies classified as nonobstructive,
      indeterminate and obstructive differed significantly (p <0.05). The
      classification of pelvicaliceal drainage varied by method for all but the most
      severely dilated systems. In individual studies classification by 1 method was
      discordant with classification by another in 19% of comparisons. Of the
      discordant interpretations 97.7% involved nonobstructive versus indeterminate or
      indeterminate versus obstructive classifications. CONCLUSIONS: Variability in
      classifying drainage patterns based on half-time requires that practitioners be
      circumspect when applying this parameter for managing asymptomatic
      hydronephrosis. It also necessitates the description of quantitative methodology
      in published series of this important clinical problem.

PMID- 10893625
TI  - Hypertension associated with multicystic dysplastic kidney in children.
AB  - PURPOSE: The results of nephrectomy for hypertension in 4 children with
      unilateral multicystic dysplastic kidney are presented. MATERIALS AND METHODS:
      The records of 3 boys and 1 girl 4 months to 4 years old with multicystic kidney
      and documented systolic hypertension leading to nephrectomy were reviewed.
      RESULTS: Blood pressure normalized after surgery in 2 patients and remained
      persistently elevated in the other 2. CONCLUSIONS: Children with multicystic
      dysplastic kidney should be screened for hypertension. Nephrectomy resolves
      hypertension in some patients with multicystic kidney.

PMID- 10893626
TI  - Extraperitoneal access for kidney transplantation in children weighing 20 kg. or
      less.
AB  - PURPOSE: We present our experience with kidney transplantation in children
      weighing 20 kg. or less. Surgery was done via extraperitoneal access while
      preserving the peritoneal cavity intact with special attention given to technical
      feasibility and the complication rate. MATERIALS AND METHODS: Included in our
      study were 46 children with a median age of 7 years weighing 20 kg. or less (mean
      16.6), of whom 16 weighed less than 15 kg. (median 13.2). The 25 boys and 21
      girls underwent a total of 49 kidney transplants, including 2 in 3 during the
      study. Donors were living related in 44 cases and cadaveric in 5. Surgical access
      was obtained by making a J-shaped pararectal incision in a curvilinear fashion
      from the symphysis pubis to near the costal border. RESULTS: Mean hospital stay
      was 22.9 days (range 6 to 83) and mean followup was 55.8 months (range 12 to
      131). All patients received water on day 1 and food on day 2 postoperatively. In
      6 patients 7 surgical complications developed, including urinary fistula in 2,
      superficial wound infection in 2 and vascular complications in 3 (renal vein
      thrombosis, stenosis and renal artery kinking in 1 each). Only 1 graft was lost
      due to a surgical complication. CONCLUSIONS: There are many advantages to using
      extraperitoneal access without an increase in surgical complications or technical
      difficulty. Absent gastrointestinal complications, an easier way to perform
      percutaneous biopsy, treatment of any surgical complication with no need for
      repeat laparotomy and the possibility of using the peritoneal cavity when
      dialysis is needed postoperatively are attractive justifications for
      extraperitoneal access.

PMID- 10893627
TI  - High incidence of a generally small kidney and primary vesicoureteral reflux.
AB  - PURPOSE: We distinguished the scintigraphy pattern of congenital reflux
      nephropathy from that of acquired scarring in children with primary
      vesicoureteral reflux. MATERIALS AND METHODS: We retrospectively evaluated the
      frequency and pattern of renal scintigraphy abnormalities in 41 patients with
      prenatally detected primary vesicoureteral reflux and in 322 with a mean age plus
      or minus standard deviation of 3.6 + or - 1 years in whom primary reflux was
      detected after urinary tract infection. Dimercapto-succinic acid scintigraphy was
      performed 4 to 6 and 1 to 4 months after reflux was diagnosed and/or the
      infection was cured in patients with urinary tract infection and prenatal
      detection, respectively. RESULTS: We identified 3 patterns of renal damage,
      including overall decreased uptake of renal radionuclide that was 20% to 40% of
      relative uptake, focal defects in uptake and shrunken kidney with relative uptake
      less than 20%. Scintigraphy revealed renal damage in 12 prenatally detected cases
      of vesicoureteral reflux, including overall decreased uptake in 58% and shrunken
      kidney in 42%, and in 111 cases of reflux detected at urinary tract infection,
      including overall decreased uptake in 50%, uptake focal defects in 37% and
      shrunken kidney in 13%. In the urinary tract infection group overall decreased
      uptake was present in 25 of 90 boys and in 40 of 232 girls (p = 0.05). Of these
      children 15% of the girls had uptake focal defects and 17% had overall decreased
      uptake. Overall decreased uptake and uptake focal defects were significantly more
      common in kidney-ureter units with reflux grade 4 or greater than in those with
      grade 3 or less (p = 0. 00001 and 0.027, respectively). CONCLUSIONS: When
      assuming that overall decreased radionuclide uptake indicates congenital reflux
      nephropathy and uptake focal defects indicate postnatal acquired scarring,
      congenital reflux nephropathy appears to be an important cause of renal damage in
      children with primary vesicoureteral reflux even beyond the neonatal age and even
      in girls. This finding is of interest because postnatally acquired scarring may
      but congenital reflux nephropathy may not be prevented.

PMID- 10893628
TI  - Segmental ureteral necrosis due to acute appendicitis.

PMID- 10893629
TI  - Long-term evaluation of rectus fascial wrap in patients with spina bifida.
AB  - PURPOSE: We evaluated patients with spina bifida to determine long-term results
      of the rectus fascial wrap, a modification of the rectus fascial sling MATERIALS
      AND METHODS: We assessed patients with spina bifida 3 years after a rectus
      fascial wrap procedure using an outcome questionnaire, renal ultrasound and
      urodynamics. RESULTS: The 15 patients who completed the outcome questionnaire
      indicated that significant improvement over preoperative status was maintained a
      mean of 58 months postoperatively. Ultrasound in 14 cases showed no postoperative
      increase in hydronephrosis. Urodynamic study in 13 patients revealed a mean
      bladder capacity of 583 cc and mean maximum detrusor pressure of 39 cm. water,
      while 11 had no urine leakage when Valsalva leak point pressure was measured.
      CONCLUSIONS: Three years postoperatively the rectus fascial wrap provides dryness
      comparable to that of other bladder neck sling procedures in patients with spina
      bifida.

PMID- 10893630
TI  - Dystopic urethral orifice into the anus in the absence of the penile urethra and
      right kidney.

PMID- 10893631
TI  - Effect of the depth and width of the urethral plate on tubularized incised plate
      urethroplasty.
AB  - PURPOSE: We determined the effect of the depth and width of the urethral groove
      on tubularized incised plate urethroplasty for distal hypospadias. MATERIALS AND
      METHODS: We retrospectively reviewed the records of 48 patients who underwent
      tubularized incised plate urethroplasty for distal hypospadias between September
      1996 and December 1998 for whom preoperative evaluation of the depth and width of
      the urethral groove was available. Patients were examined by an independent
      clinician a median of 28 months after surgery when the neourethra was calibrated
      and urinary stream assessed. RESULTS: Of the 48 patients 46 were available for
      clinical examination. The urinary stream was straight in 40 boys and angled in 8,
      while none sprayed. Urethral fistula developed in 6 patients with a urethral
      plate of less than 8 mm. wide (p = 0.001). The urethral groove was deep in 13
      cases, moderate in 20 and shallow in 15. There were no differences among these 3
      groups in regard to urinary stream direction or fistula rate. Of the boys with a
      shallow urethral groove 6 (40%) have a neourethral caliber of 6Fr or less versus
      3 (15%) with a moderate and 0 with a deep groove. This difference was
      statistically significant (p = 0.028). Each patient in whom meatal stenosis
      developed had a shallow urethral groove. CONCLUSIONS: Urethral groove depth
      appears to influence neourethral caliber after tubularized incised plate
      urethroplasty. A shallow groove predisposes to a narrower neourethra and meatal
      stenosis subsequently. We observed no evidence that incising the urethral plate
      increases the final urethral diameter. Urethral fistula after tubularized incised
      plate urethroplasty was associated with an initially narrow urethral plate.

PMID- 10893632
TI  - Female epispadias repair: a new 1-stage technique.
AB  - PURPOSE: Female epispadias is a rare anomaly. According to the literature it is
      usually treated with staged procedures, including bladder neck reconstruction, to
      achieve continence. We developed a 1-stage surgical technique that offers the
      possibility of achieving continence and a cosmetically normal appearance of the
      vulva. MATERIALS AND METHODS: We treated 4 patients 4 months to 8 years old. The
      main point of the technique is to free completely the urethral plate and bladder
      neck from surrounding tissue. After tubularizing the urethral plate into a
      urethra modified needle suspension brings the bladder neck and proximal urethra
      into the intra-abdominal position. The pelvic floor is then reconstructed between
      the anterior vaginal wall and urethra. Thus, continence may be attained by intra
      abdominal positioning of the bladder neck and proximal urethra as well as by
      pelvic floor reconstruction. RESULTS: Of our 4 consecutive cases of primary
      untreated epispadias the technique proved successful in 3, while followup is too
      short in 1. One patient is completely dry and voids without a further procedure.
      Postoperatively 2 patients with 5 years or more of followup required injection of
      a bulking agent at the bladder neck level to achieve continence, including 1 who
      is damp during the day without the need to change clothes and 1 on clean
      intermittent catheterization twice daily because post-void residual urine volume
      causes recurrent urinary tract infection. CONCLUSIONS: The described technique is
      promising for treating this disabling anomaly.

PMID- 10893633
TI  - Penile adhesions after neonatal circumcision.
AB  - PURPOSE: The appropriate management of penile adhesions in circumcised boys is
      unclear. An important consideration is whether adhesions resolve spontaneously.
      We studied the incidence of penile adhesions as a function of patient age to
      assess the natural history. MATERIALS AND METHODS: We evaluated all circumcised
      boys presenting to our pediatric urology clinic. A standard form was used to
      classify adhesions as grade 0-no adhesions, 1-fine adhesions to the corona, 2
      adhesions covering less than 50% of the glans and 3-adhesions covering greater
      than 50% of the glans. All boys were evaluated by 1 of 2 pediatric urologists.
      Previous treatment of adhesions was assessed and skin bridges were also noted.
      RESULTS: We enrolled in our study 254 boys 1 month to 19 years 8 months old. Only
      7 patients had a history of treatment of adhesion, of whom 3 had recurrent
      adhesions at evaluation. Patients were divided into groups based on age,
      including younger than 12 months (61), 13 to 60 (78), 61 to 108 (51) and 109
      months old or older (64). In these groups we noted an adhesion rate of 71%, 28%,
      8% and 2%, respectively. The rate of adhesions more severe than grade 1 was 30%,
      10% and 0% in boys 12 months old or younger, 13 to 60 and 61 months old or older,
      respectively. The oldest patient with grade 3 adhesions was 31 months old. Skin
      bridges in 6 cases involved the circumcision line in 4. CONCLUSIONS: Penile
      adhesions develop after circumcision and the incidence decreases with patient
      age. Although there is debate on whether to lyse these adhesions manually, our
      findings suggest that adhesions resolve without treatment. Based on our results
      we do not recommend lysing penile adhesions, except perhaps those involving the
      circumcision line.

PMID- 10893634
TI  - Testicular position in the androgen insensitivity syndrome: implications for the
      role of androgens in testicular descent.
AB  - PURPOSE: We compared testicular position with genital phenotype in a clinical
      series and a literature review of androgen receptor mutations to assess the role
      of androgens in testicular descent. MATERIALS AND METHODS: Our clinical reports,
      the androgen receptor mutations database and selected literature were reviewed.
      Subjects with a proved androgen receptor mutation were included in our study when
      a female or ambiguous phenotype was present (Quigley grade 3 to 7) and testicular
      position was documented. Comparison among groups was done by Fisher's exact or
      chi-square test. RESULTS: Of the 7 patients with detailed clinical records 5 had
      abdominal (bilateral in 4) and 2 had bilateral inguinal testes. Four patients
      with abdominal testes also had aberrant pelvic ligaments extending medially from
      the gonads. Including an additional 102 cases identified in the literature,
      abdominal testes were present in 52% and 3% of those with complete and partial
      androgen insensitivity, respectively. The incidence of abdominal testes was
      highest (86%) in patients with a complete female phenotype and no pubic hair
      (grade 7). It decreased significantly with increasing masculinization and was
      higher in phenotypic females diagnosed at or after (67%) than in those identified
      before (22%) puberty. Hernia was associated with inguinal and abdominal testes.
      CONCLUSIONS: Testicular position correlates with genital phenotype in patients
      with androgen receptor mutations, supporting a major role for androgens in
      testicular descent. Inguinal hernia and abnormal pelvic ligaments in these
      individuals may partially determine testicular position but to our knowledge the
      role of androgen receptors, if any, in their development is unknown.

PMID- 10893635
TI  - Expression of the VEGF-receptor Flt-1 in benign, premalignant and malignant
      prostate tissues.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is one of the most potent
      regulators of angiogenesis and has been shown to act upon two tyrosine kinase
      family receptors: c-fms-like tyrosine kinase (Flt-1) and fetal liver kinase.
      Preliminary reports have emphasized that expression of VEGF receptors is
      endothelial cell-specific. In this study we verified the localization and
      distribution of Flt-1 protein and mRNA expression in prostatic adenocarcinoma
      (CaP) as well as prostate intraepithelial neoplasia (PIN) and benign prostatic
      hyperplasia (BPH). MATERIALS AND METHODS: 30 selected surgical specimens
      exhibiting areas with CaP, PIN and BPH histology were evaluated for Flt-1 protein
      expression by immunohistochemistry. Results were compared with tumor
      differentiation (Gleason-Score), serum-PSA and clinical followup. Flt-1 synthesis
      by prostatic carcinoma cell lines, freshly isolated BPH epithelial cells (BPH-EC)
      and stromal cells was investigated using RT-PCR and intron spanning primer.
      RESULTS: VEGF receptor Flt-1 specific anti-sera revealed significant staining of
      prostatic endothelial cells, but the reactivity was not restricted to endothelial
      cells. BPH-epithelial cells of all specimens reacted significantly with anti-Flt
      1. In contrast, tumor cells failed to react with anti-Flt-1 in 56% of the
      specimens. BPH-EC revealed a uniform anti-Flt-1 reactivity, which was less
      pronounced and weaker in PIN. Loss of anti-Flt-1 reactivity of prostatic tumor
      cells did not correlate with preoperative PSA serum levels but increased with
      tumor dedifferentiation. Interestingly, tumor cells of all CaP specimens with a
      Gleason score of >8 exhibit no anti-Flt-1 immunoreactivity. Accordingly while
      PC3, DU145 and LNCaP cells were negative when tested using RT-PCR all BPH tissue
      derived BPH-EC revealed Flt-1 coding mRNA expression. CONCLUSIONS: Widespread
      distribution of VEGF receptor Flt-1 in BPH, PIN and prostate cancer specimens
      suggests that VEGF function in prostate is not restricted to endothelial cells
      and angiogenesis. However, since the receptor is lost in CaP cells and with tumor
      dedifferentiation, these yet unknown effects of VEGF on epithelial cells are
      obviously suppressed with malignant transformation.

PMID- 10893636
TI  - Cell proliferation, apoptosis, Bcl-2 and Bax expression in obstructed opossum
      early metanephroi.
AB  - PURPOSE: Complete ureteral obstruction (CUTO) in the fetal kidney induces tubular
      and glomerular cysts, interstitial fibrosis, and halts renal development.
      Previous studies have shown that apoptosis is a predominant mechanism in the
      chronically injured kidney following obstruction, but the precise cellular and
      molecular mechanisms are poorly understood. MATERIALS AND METHODS: We have used
      CUTO in opossum pups with early metanephric kidneys, sacrificed at two weeks, to
      evaluate the role of cell proliferation, apoptosis and apoptosis regulating
      genes, Bcl-2 and Bax. RESULTS: Obstructed fetal kidneys demonstrate high
      apoptosis in the renal pelvis and tubulointerstitium, compared with sham operated
      animals. Apoptosis is accompanied by statistically significant increased cell
      proliferation in the interstitium but not in tubules. Apoptosis in the tubules is
      accompanied by increased Bax and decreased Bcl-2 staining. In the nephrogenic
      zone apoptosis is increased, even though it is not statistically significant. Bcl
      2 and Bax in the nephrogenic zone are unchanged compared with sham, but cell
      proliferation is increased. CONCLUSIONS: We suggest that abnormal patterns of
      cell kinetics may contribute to disease pathogenesis in the obstructed fetal
      kidney.

PMID- 10893637
TI  - Induction of apoptosis in BPH stromal cells by adenoviral-mediated overexpression
      of caspase-7.
AB  - PURPOSE: We hypothesized that expression/activity of critical components of the
      apoptotic pathway can be used to induce apoptosis of a human prostate cell line
      derived from benign prostatic hyperplasia (BPH) tissue. MATERIALS AND METHODS: We
      analyzed the apoptotic pathway in BPH cells treated with the powerful inducer of
      apoptosis, staurosporine (STS), and adenoviruses overexpressing caspase-3, -7, or
      the control gene lacZ. RESULTS: Twelve hours post-STS, most BPH cells were
      floating in the culture medium, TUNEL staining was widespread, and DEVDase
      activity (the catalytic activity of type II caspases) was increased. The pan
      caspase inhibitor, Z-VAD-FMK, prevented STS-induced apoptosis. Based on these
      observations, we performed immunoblot analysis for the three known group II
      caspases (that is caspase-2, -3 and -7), but none of them was detected with three
      commercially available antibodies. Nevertheless, in view of the presence of
      increased DEVDase activity, we reasoned that a group II caspase must be a
      critical mediator of apoptosis in this model. If correct, we postulated that
      overexpression and activation of a type II caspase should cause apoptosis. To
      test this hypothesis, we coupled the cDNAs encoding caspase-3 and caspase-7 to
      adenoviral vectors and obtained constructs AvC3 and AvC7. Cells infected with
      AvC3 or AvC7 overexpressed the protein for caspase-3 or -7 within 24 to 48 hours.
      Caspase-3 overexpression did not cause apoptosis above that observed in cells
      receiving the control adenovirus expressing the lacZ cDNA (AvLac-Z). In contrast,
      caspase-7 overexpression induced massive apoptosis. BPH cells were then infected
      with increasing multiplicity of infection (MOI) of AvC7 and AvlacZ. A positive
      correlation was found between the amount of caspase-7 expressed and the level of
      DEVDase activity measured. AvC7 at MOIs of 25:1 and 50:1 induced apoptosis in
      about 50% of BPH cells at 72 hours post-infection. This effect was AvC7 specific,
      because the same MOIs of AvlacZ were not apoptogenic. CONCLUSIONS: Adenoviral
      mediated overexpression of caspase-7 induces apoptosis of BPH-derived cells.

PMID- 10893638
TI  - Murine IL-2 secreting recombinant Bacillus Calmette-Guerin augments macrophage
      mediated cytotoxicity against murine bladder cancer MBT-2.
AB  - PURPOSE: This study was to establish a more effective anti-cancer
      immunomodulating agent by constructing recombinant (r) Bacillus Calmette-Guerin
      (BCG) secreting alpha-antigen (alpha-Ag) fused murine (m) interleukin (IL)-2, and
      to study its biological activity on cell-mediated cytotoxicity against murine
      bladder cancer cell, MBT-2, in vitro. MATERIALS AND METHODS: pSO246 plasmid
      vector ligated with mIL-2 gene was introduced into BCG by electroporation.
      Thioglycollate-elicited murine peritoneal exudate cells (PEC) were stimulated in
      vitro with parental BCG or rBCG and their cytotoxic activity and the cytokine
      production was studied. Cytokines were assayed by an enzyme-linked immunosorbent
      assay (ELISA) and L929 bioassay. Cytotoxicity was measured by 51Cr releasing
      assay. RESULTS: rBCG (alpha-Ag-IL-2) secreted functional IL-2 and augmented more
      efficient cytotoxicity to MBT-2 and cytokines such as IL-12, tumor necrosis
      factor and interferon (IFN)-gamma in PEC than parental BCG did. rBCG (alpha-Ag)
      had the same activity as BCG. Anti-IL-2 antibody reduced rBCG (alpha-Ag-IL-2)
      mediated cytotoxicity and IFN-gamma production. Exogenous IL-2 also enhanced BCG
      mediated cytotoxicity, but 100 times more IL-2 was required to express the same
      activity as rBCG (alpha-Ag-IL-2). Anti-IL-12 neutralizing antibody and the
      depletion of T cells and NK cells reduced IFN-gamma production by PEC stimulated
      with rBCG (alpha-Ag-IL-2), suggesting that T cells, NK cells and IL-12
      participate in the enhancement of IFN-gamma production. CONCLUSIONS: rBCG
      secreting IL-2 showed significant antitumor activity and cytokine production and
      this will be a promising agent for bladder cancer patient to reduce both clinical
      dose and side effects of BCG for immunotherapy.

PMID- 10893639
TI  - Detection of hematogenous micrometastasis in patients with transitional cell
      carcinoma.
AB  - PURPOSE: Cytokeratin 20 (CK 20) is selectively expressed in urothelium, gastric
      intestinal epithelium, in Merkel cells and in a variety of malignant neoplasms.
      CK 20 RT-PCR assay has been extensively used to detect isolated cancer cells in
      peripheral blood, lymph nodes and bone marrow samples of patients with colorectal
      carcinoma. Since CK-20 is also actively expressed in transitional cell carcinoma
      (TCC), we analyzed, whether CK 20 Reverse Transcriptase Polymerase Chain Reaction
      (RT-PCR) is suitable to detect residual tumor cells in patients with transitional
      cell carcinoma of the bladder and the upper urinary tract. MATERIALS AND METHODS:
      Nested Reverse Transcriptase Polymerase Chain Reaction assay was used to analyze
      CK 20 transcripts in peripheral venous blood samples and tumor biopsies of 49
      patients with transitional cell carcinoma. Blood samples of 22 healthy volunteers
      served as negative controls. RESULTS: CK 20 mRNA was detectable in blood samples
      of 12 of 49 patients with TCC. All blood samples of the control group tested
      negative. The detection rate for CK 20 mRNA significantly correlated (p = 0.0019,
      Cochran-Armitage Trend Test) to the stage of disease and increased from 0% in
      stage pTa to 63% in stage pT4. CONCLUSIONS: These results suggest that CK 20 is a
      suitable marker for the detection of disseminated TCC cells in peripheral venous
      blood samples and may be helpful in the molecular staging of TCC patients. The
      prognostic relevance has to be evaluated in further followup.

PMID- 10893640
TI  - Acoustic and mechanical properties of artificial stones in comparison to natural
      kidney stones.
AB  - PURPOSE: Standardized and reproducible artificial kidney stone models are
      important for performing comparative studies of different lithotripsy modalities.
      The acoustic and mechanical properties of renal calculi dictate the manner by
      which stones interact with the mechanical stresses produced by shock wave
      lithotripsy (SWL) or intracorporeal lithotripsy modalities. We have developed a
      novel artificial kidney stone model that is made of natural substances found in
      real kidney stones. These stone models appear to be much closer in physical
      properties to natural kidney stones than previously used stone models. MATERIALS
      AND METHODS: The acoustic and mechanical properties of six groups of artificial
      stone models were compared to corresponding natural stones of similar
      compositions. Moreover, three groups of artificial stone models made of plaster
      of-Paris were compared to their natural counterparts. In terms of acoustic
      properties, stone density was measured using a pycnometer based on Archimedes'
      principle, whereas longitudinal and transverse (or shear) wave propagation speeds
      were measured using an ultrasound pulse transmission technique. These values were
      used to calculate wave impedance and dynamic mechanical properties (bulk modulus,
      Young's modulus, and shear modulus) of the stones. The microhardness of the
      stones was measured and the effect of composition on stone fragility was
      evaluated. RESULTS: Artificial stones, when compared to natural stones of similar
      composition, showed similar trends in longitudinal and transverse wave speeds,
      wave impedance, and dynamic elastic moduli. However, values for the artificial
      stones were uniformly low compared to those of natural stones, suggesting that
      these artificial stones may be more amenable to shock wave fragmentation. The
      results of SWL on stone fragmentation of artificial and natural stones also
      revealed similar trends with the exception of artificial cystine stones which
      were found to be the most resistant to shock wave fragmentation. CONCLUSIONS: The
      results indicate that the physical properties of artificial stones made of
      natural stone materials are comparable to renal calculi of the same chemical
      composition. The data suggests that these stone phantoms are suitable for
      performing standardized and reproducible in vitro investigations, especially with
      regards to fragility of kidney stones of different chemical compositions during
      SWL.

PMID- 10893641
TI  - Intravesical oxyhemoglobin initiates bladder overactivity in conscious, normal
      rats.
AB  - PURPOSE: To investigate whether intravesical oxyhemoglobin, a nitric oxide
      scavenger, changes bladder activity in normal rats. MATERIALS AND METHODS:
      Oxyhemoglobin was given intravesically at different concentrations to conscious,
      female Sprague-Dawley rats undergoing continuous cystometry. RESULTS:
      Intravesical oxyhemoglobin increased bladder activity in a concentration
      dependent way. At a concentration of 2.5 x 10-4 M (n = 8), micturition pressure
      (p <0. 01), basal pressure (p <0.01), and residual volume (p <0.05) increased,
      and bladder capacity (p <0.001) and micturition volume (p <0.001) decreased. The
      effect of oxyhemoglobin was reduced or abolished by L-arginine (200 mg./kg.-1),
      given intra-arterially near the bladder, and was enhanced by the guanylate
      cyclase inhibitor, ODQ (0.5 and 1 mg./kg.-1). The K+ channel opener, ZD6169 100
      ng.ml. -1, given intravesically for 1 hour prior to instillation of
      oxyhemoglobin, reduced or completely prevented the bladder activity induced by
      oxyhemoglobin. CONCLUSIONS: Intravesical oxyhemoglobin induces bladder
      overactivity, probably by interfering with nitric oxide (NO) generated in the
      urothelium or suburothelially. NO may be involved in the regulation of the
      threshold for afferent firing in the bladder.

PMID- 10893642
TI  - Novel test lead designs for sacral nerve stimulation: improved passive fixation
      in an animal model.
AB  - PURPOSE: To evaluate the ability of two novel coiled test stimulation lead
      designs to reduce or eliminate undesired migration and concomitant loss or
      attenuation of responsiveness to sacral nerve stimulation (SNS) associated with
      standard percutaneous nerve evaluation (PNE) leads. MATERIALS AND METHODS: The
      two novel leads (Coiled Leads 1 and 2) and a standard PNE lead were inserted
      bilaterally in sacral foramina of female goats. At various times thereafter
      threshold voltage responses were measured. Prior to lead removal, distance of
      lead migration was evaluated by x-ray imaging and the force necessary to displace
      the leads measured. Thereafter, as the leads were being removed, the force
      necessary for removal was also measured. RESULTS: Migration was consistently
      either nil or minimal for both coiled leads. In contrast, migration of the
      standard lead occurred in all cases and was substantial in magnitude. A
      significant linear association was evident between the migration distance of the
      standard lead and the corresponding voltages needed to evoke a response. The
      forces necessary to displace Coiled Lead 1 and Coiled Lead 2 were both
      significantly higher (p <0.01) than those for the standard lead. In some cases
      comparatively high forces were needed for removal of Coiled Lead 1 but not Coiled
      Lead 2. CONCLUSIONS: Coiled lead designs appear to offer a potentially promising
      alternative to standard leads for PNE, allowing a wider range of patients to be
      correctly identified as candidates for sacral root neuromodulation. Coiled Lead 2
      merits further investigation in human subjects.

PMID- 10893643
TI  - Renin angiotensin system of rabbit clitoral cavernosum: interaction with nitric
      oxide.
AB  - PURPOSE: Angiotensin (ANG) II has been known to be a potent modulator for the
      maintenance of smooth muscle tone of the penile cavernosum. However, its role in
      clitoral cavernosum is unknown. The clitoris is the homologue of the penis
      arising from the embryological genital tubercle. We investigated the presence of
      ANG II receptors, the function of ANG II, and its interaction with nitric oxide
      (NO) in rabbit clitoral cavernosum. MATERIALS AND METHODS: The isometric tension
      was measured in the strips of clitoral cavernosum. Reverse transcriptase
      polymerase chain reaction (RT-PCR) was used to evaluate expression of AT1a and
      AT1b ANG II receptor subtype mRNAs. In vitro autoradiography was used to localize
      ANG II receptors in the clitoral cavernosum. RESULTS: The clitoral cavernosum was
      contracted dose-dependently by the addition of ANG II. Dup 753 (ANG II type 1
      receptor antagonist) inhibited significantly ANG II induced contraction. PD
      123,319 (ANG II type 2 receptor antagonist) did not affect the ANG II response.
      Pretreatment with NG-nitro-L-arginine methyl ester (NO synthase inhibitor)
      accentuated contractions induced by ANG II. Specific binding sites for 125I-ANG
      II were found in the clitoral cavernosum. The dissociation constant (Kd) was 0.58
      + or - 0.05 nM. Specific binding of 125I-ANG II was displaced by Dup 753 (10-5 M)
      but not by PD 123,319 (10-5 M). The inhibitory constant (Ki) for Dup 753 was 23.
      4 + or - 9.73 nM and mRNAs for AT1a and AT1b receptor subtypes were detected by
      RT-PCR. CONCLUSION: The present study shows that ANG II is involved in the
      regulation of clitoral cavernosum smooth muscle tone via ANG II receptor subtype
      AT1, and that ANG II has cross-talk with NO.

PMID- 10893644
TI  - Tmp21-I, a vesicular trafficking protein, is differentially expressed during
      induction of the ureter and metanephros.
AB  - PURPOSE: To identify genes participating in the reciprocal induction of the
      metanephros and ureter. MATERIALS AND METHODS: Embryonic day 14 Sprague-Dawley
      rat kidneys and ureters were microdissected into differentiating mesenchyme,
      ureteric buds, and extrarenal ureter and prepared for RT/PCR differential
      display. Differentially displayed cDNAs were reamplified, cloned, and sequenced.
      Expression was verified in the embryonic, newborn or adult kidneys by Northern
      blot hybridization or RT/PCR using sequence specific primers. A newborn rat
      kidney cDNA library was prepared and screened with probes of interest. Positive
      clones were screened, sequenced and compared to the GenBank/EMBL databases. A
      rabbit polyclonal antibody was raised to a synthetic peptide of the Tmp21-I
      protein and was used for immunohistochemistry. RESULTS: From the cDNAs
      differentially displayed by the ureteric buds cDNA B11, is 254 bp in length. The
      gene for B11 is expressed in adult and newborn kidneys as two transcripts (3.4 kb
      and 1.3 kb). More importantly, RT/PCR on E14 kidneys using B11 sequence specific
      primers identified expression in the embryonic kidney at the beginning of
      induction. B11 cDNA library screening yielded clones with inserts of 1.3 kb. This
      sequence encodes Tmp21-I, a vesicular trafficking protein. Immunohistochemistry
      demonstrates that Tmp21-I is abundant in the nephrogenic cortex of the newborn
      kidney and as a nephron matures, the protein levels decline. The protein is
      essentially absent in the adult rat kidney. CONCLUSIONS: Tmp21-I is a
      developmentally regulated gene expressed during kidney induction. Localized
      within the nephrogenic zone, it may direct the intracellular trafficking or
      secretion of proteins responsible for nephrogenesis.

PMID- 10893645
TI  - Significance of the CAG repeat polymorphism of the androgen receptor gene in
      prostate cancer progression.
AB  - PURPOSE: The CAG repeat polymorphism of the androgen receptor gene has been
      associated with an increased prostate cancer risk, and the repeat length
      correlated with cancer stage and grade at presentation. Men with an allele length
      of </= 18 CAG repeats have a 2-fold increase in risk for high-stage or high-grade
      prostate cancer, compared with patients with a longer CAG repeat. We examined the
      significance of the CAG repeat polymorphism of the androgen receptor gene for
      predicting prostate cancer progression among 318 patients treated by radical
      prostatectomy for clinically localized prostate cancer between 1987 and 1994.
      MATERIALS AND METHODS: Leukocyte DNA was collected and genotyping of the CAG
      repeat polymorphism was performed using a PCR-based direct sequencing method.
      Risk ratios were calculated for developing biochemical recurrence for patients
      associated with an allele length of </= 18 CAG repeats, compared with patients
      with an allele length of >18 CAG repeats, controlling for grade, stage and serum
      PSA level at diagnosis using Cox proportional hazard modeling. RESULTS: Overall,
      the CAG repeat allele was not predictive of recurrence; tumor grade, stage and
      PSA level at diagnosis were the only predictors of recurrence in a multivariate
      analysis. However, for patients at low risk for recurrence (Gleason score 2 to 6,
      stage pT2, and PSA </= 10 ng./ml.), the relative risk of recurrence associated
      with an allele of </= 18 CAG repeats was 8.07 (95% C.I., 2.02 to 32.2, p =
      0.004), compared with patients with an allele length of >18 CAG repeats. In
      contrast, for patients at high risk of recurrence (Gleason score >/= 7, stage
      pT3/4, or PSA >10 ng./ml.), the relative risk associated with the </= 18 CAG
      repeat allele was 0.72 (95% C.I., 0.33 to 1.57, p = 0.41), compared with patients
      with the >18 CAG repeat allele. CONCLUSIONS: The length of the CAG repeat
      polymorphism of the androgen receptor gene may be important for prostate cancer
      recurrence among patients who are otherwise at low risk for recurrence after
      radical prostatectomy. These findings have potential implications for patient
      selection for adjuvant treatment, and for the development of novel treatments.

PMID- 10893646
TI  - Plasma levels of cavernous and systemic norepinephrine and epinephrine in men
      during different phases of penile erection.
AB  - PURPOSE: Knowledge of the functional anatomy, hemodynamics, neurophysiology and
      pharmacology of penile erection has improved tremendously during the last 2
      decades. However, only few in vivo studies on human peripheral neurotransmission
      have been carried out up until now. Therefore, we conducted a study to examine
      plasma levels of catecholamines norepinephrine (NE) and epinephrine (E) in the
      peripheral and cavernous blood of healthy men during penile flaccidity and in
      different phases of erection. MATERIALS AND METHODS: Blood samples were drawn
      simultaneously from the corpus cavernosum (CC) and the cubital vein (P) in 53
      healthy volunteers with normal erectile function, in four different functional
      states of the cavernous erectile tissue (flaccidity = 1, tumescence = 2, rigidity
      = 3, detumescence = 4). Penile erections were induced by audiovisual and tactile
      stimulation and the plasma concentrations of NE and E were determined by means of
      a radioimmunoassay (RIA). RESULTS: A significant (p <0.001) reduction of NE in CC
      plasma was found from flaccidity (362 + or - 173 pg./ml.) to rigidity (248 + or -
      122 pg./ml.), followed by an increase in the detumescence phase (336 + or - 199
      pg./ml.), (p <0.001). In contrast, changes in NE levels in the peripheral plasma
      were less pronounced from 1P (202 + or - 102 pg./ml.) to 3P (229 + or - 118
      pg./ml.), (p = 0.006) and from 3P to 4P (222 + or - 127 pg./ml.), respectively (p
      = 0.370). The most pronounced increase in cavernous E levels were observed from
      flaccidity (47 + or - 41 pg. /ml.) to tumescence (130 + or - 106 pg./ml.) (p
      <0.001). Cavernous E levels dropped significantly from 113 + or - 67 pg./ml.
      during rigidity to 76 + or - 57 pg./ml. + or - during detumescence (p <0.001).
      The course of peripheral plasma levels of E was similar to that in the cavernous
      blood. Mean peripheral E level was 69 + or - 55 pg./ml. in the state of penile
      flaccidity, reaching 98 + or - 78 pg./ml. in tumescence and 82 + or - 64 pg./ml.
      in rigidity (p <0.001), respectively, and finally decreasing to 62 + or - 46
      pg./ml. in detumescence. CONCLUSION: Penile erection, based on the relaxation of
      cavernous and arterial smooth muscle, is accompanied by a significant reduction
      of NE in cavernous blood, while E levels rose in peripheral and cavernous blood
      during developing erection.

PMID- 10893647
TI  - Tissue selectivity of KMD-3213, an alpha(1)-adrenoreceptor antagonist, in human
      prostate and vasculature.
AB  - PURPOSE: We evaluated the binding and functional affinity of KMD-3213 and other
      alpha 1-adrenoceptor (AR) antagonists such as prazosin or tamsulosin, to compare
      the tissue selectivity of these antagonists between human prostate and
      vasculature. MATERIALS AND METHODS: In the binding experiments, saturation
      experiments using [3H]-KMD and [3H]-prazosin (PZ) were performed, and competition
      of [3H]-PZ binding by antagonists was also examined in human prostatic and aortic
      membranes. In the functional study, contractile responses to noradrenaline were
      evaluated in human prostate and mesenteric artery. RESULTS: [3H]-PZ bound to
      human prostatic and aortic membranes with subnanomolar affinity. [3H]-KMD also
      bound to human prostate, with higher affinity than [3H]-PZ; whereas it did not
      bind sufficiently to human aorta. Competition of [3H]-PZ binding revealed that
      KMD-3213 had more than 200-fold higher affinity for human prostate than for
      aorta. Binding profiles of antagonists revealed that human prostate predominantly
      expressed alpha 1A-AR, whereas human aorta expressed alpha 1B-AR mainly. In
      functional experiments, KMD-3213 potently inhibited the noradrenaline-induced
      contraction in human prostate as potently as tamsulosin, although prazosin showed
      relatively low affinity. Comparing these functional affinities with those in the
      mesenteric artery, only KMD-3213 exhibited substantial tissue selectivity,
      showing more than 100-fold higher affinity for human prostate than for mesenteric
      artery. Functional affinity of each antagonist suggested that noradrenaline
      induced contractions were mainly mediated by alpha 1L-AR in the human prostate
      and by alpha 1B-AR in the mesenteric artery. CONCLUSION: These results suggest
      that KMD-3213 is a substantially prostate-selective alpha 1-AR antagonist in
      human tissues compared with other alpha 1-AR antagonists.

PMID- 10893649
TI  - Focus on risperidone.
AB  - Risperidone is a relatively new antipsychotic available world-wide since the
      early 1990s. It has been characterised as atypical, but shares some of the
      extrapyramidal side-effect profile of the earlier antipsychotics, when used at
      doses higher than those recommended by the manufacturer (4-6 mg/day). There is
      now adequate comparison with conventional antipsychotics to suggest its
      superiority, but a depot formulation is needed to complete the picture.

PMID- 10893648
TI  - Rapid diagnosis of genitourinary tuberculosis by polymerase chain reaction and
      non-radioactive DNA hybridization.
AB  - OBJECTIVE: To establish a polymerase chain reaction (PCR) assay for the rapid
      detection and identification of mycobacteria in urine, and to assess the value of
      such assay in routine laboratory diagnosis of genitourinary tuberculosis.
      MATERIALS AND METHODS: Urine specimens from 1000 patients with clinical suspicion
      of urinary tuberculosis were examined. Two assays for the detection and
      identification of Mycobacterium tuberculosis (M. tuberculosis) complex and
      mycobacteria other than tuberculosis (MOTT) by non-radioactive DNA hybridization
      of PCR-product were applied. The first assay used PCR primers and probe derived
      from M. tuberculosis species-specific DNA insertion sequence, IS6110. The second
      utilized mycobacterium genus-specific sequence encoding ribosomal ribonucleic
      acid (16S rRNA). The results obtained by PCR were compared with those obtained by
      standard microbiological methods, acid-fast bacilli (AFB) stain and culture.
      RESULTS: Compared with cultures, the sensitivity of AFB staining was 52.07% and
      the specificity was 96.7%. In comparison to the results of culture, the overall
      sensitivity and specificity of the IS6110-PCR assay was 95.59% and 98.12%
      respectively. While the corresponding results for the 16S rRNA gene-PCR were
      87.05% and 98. 9%. CONCLUSION: The high sensitivity and specificity in addition
      to the potential for rapid detection of mycobacteria, makes this test a useful
      tool in the clinical management of mycobacterial infection in urine. Urine
      specimens may contain M. tuberculosis and/or other mycobacteria; therefore, there
      are advantages in using genus-specific primers in parallel with species-specific
      primers in PCR assay.

PMID- 10893650
TI  - Using angiotensin converting enzyme inhibitors in African-American hypertensives:
      a new approach to treating hypertension and preventing target-organ damage.
AB  - Angiotensin converting enzyme (ACE) inhibitors have been avoided as an initial
      therapeutic option in the treatment of hypertension in African-Americans. A major
      reason for this has been the widespread perception of clinicians that these
      agents have poor blood pressure (BP) lowering efficacy in this population.
      Remarkably uniform and pervasive interpretations of clinical trial data have
      formed the basis of this clinical perception and can be summarised as follows:
      (1) there has been a lesser BP lowering effect of ACE inhibitors in African
      Americans compared to whites, particularly at low doses; and (2) short-acting ACE
      inhibitors like captopril prescribed at the midpoint of its maximal total daily
      dose lower BP less effectively than higher doses of calcium antagonists in
      African-Americans. A reinterpretation of published data from these same clinical
      trials suggests that: (1) the majority of African-Americans have meaningful BP
      responses to ACE inhibitors, albeit at a higher average dose than in whites; and
      (2) high levels of dietary sodium intake appear to explain a significant portion
      of the racial differences in BP response at the lower doses of ACE inhibitors.
      Thus, ACE inhibitors can effectively lower BP in African-Americans. These data
      suggest that the clinician should not avoid these agents in African-Americans
      because of a presumed lack of BP lowering efficacy. Rather, we should recognise
      the importance of adequate drug dosing and modest reductions in dietary sodium
      intake in augmenting the BP lowering effect of ACE inhibitors in hypertensive
      African-Americans.

PMID- 10893651
TI  - Cerivastatin gender effect: sub-analyses of results from a multinational,
      randomised, double-blind study. Cerivastatin Study Group.
AB  - We previously reported the results of a multicentre, randomised, double-blind,
      parallel-group study comparing the efficacy and safety of cerivastatin 0.4 mg/day
      and cerivastatin 0.2 mg/day in patients with primary hypercholesterolaemia.
      Exploratory analysis in this study suggested a gender difference in the 0.4 mg
      group: mean low-density lipoprotein cholesterol (LDL-C) decreased by 44.4 +/-
      8.9% in women, compared with a mean decrease of 37.0 +/- 0.9% in men (p < 0.046).
      This paper reports the results of further sub-analyses from this study. Overall
      in the per-protocol (PP) population, 71.5% (n = 73) of women taking cerivastatin
      0.4 mg had an LDL-C decrease of > 40%, compared with 38.0% (n = 76) of men taking
      the same dose. In the cerivastatin 0.2 mg PP population, 34% (n = 17) of women
      had an LDL-C decrease of > 40%, compared with 19% (n = 18) of men. Mean LDL-C/HDL
      C ratio decreased by 43% from baseline to the end of the study in the
      cerivastatin 0.4 mg PP group: -41.3% in males vs. -48.3% in females. In the
      cerivastatin 0.2 mg group, the decrease in LDL-C/HDL-C ratio from baseline to
      endpoint did not markedly differ between genders: -37.0% for males vs. -37.3% for
      females. Categorial analysis of the LDL-C/HDL-C ratio found that 90% of PP
      patients taking cerivastatin 0.4 mg, and 84% of PP patients taking cerivastatin
      0.2 mg, had a low CHD risk (defined as a LDL-C/HDL-C ratio < or = 3) after 8
      weeks of treatment. The 6th and 95th percentiles of the distribution of LDL-C
      reduction from baseline revealed that 90% of PP patients taking cerivastatin 0.4
      mg had an LDL-C reduction of between 22% and 56%. The mean LDL-C reduction for
      this 90% subset of patients was 40.1%. The same analysis for PP patients taking
      cerivastatin 0.2 mg found that 90% had an LDL-C reduction of between 13% and 49%.
      The mean LDL-C reduction in this 90% subset of patients was 31.5%. Of the
      patients taking cerivastatin 0.4 mg and valid for treatment according to National
      Cholesterol Education Program (NCEP) criteria, 71% (149/211) achieved NCEP
      targets for LDL-C at Week 16.

PMID- 10893652
TI  - A novel hypothesis regarding the evolutionary origins of the immunoglobulin fold.
AB  - The recent cloning of two cDNAs (Clone 1 and Clone 5) that encode novel
      hypothetical proteins, combining an N-terminal Ig kappa-like domain with features
      that occur in microfibril-associated glycoproteins (MAGPs) and fibrinogen, raises
      the question of whether the Ig fold may have originated in association with
      functions that may be more primitive than soluble immunity. Pairwise alignments
      were performed to compare similarities of fibrinogen-beta, Clone 1 and an Ig
      kappa sequence. Clone 1 had two regions in its Ig domain with > 50% similarity to
      fibrinogen, while Ig kappa was virtually non-homologous to fibrinogen. This
      result suggests that Clone 1 is closer to their common ancestor. A neighbour
      joining tree was computed, and it supported this interpretation. Three
      dimensional modelling of the most highly conserved sequence revealed two
      antiparallel beta strands connected by a helix. These observations suggest that
      the ancestral gene for the immunoglobulin superfamily may have originated as a
      primitive sandwich-like fold, possibly used in matrix/cell communications.

PMID- 10893653
TI  - Efficacy and tolerability of a low-dose of Oesclim (25 mcg daily) in the
      management of symptomatic menopausal women: a French open-label study.
AB  - OBJECTIVE: To establish the proportion of symptomatic postmenopausal women, whose
      HRT treatment is initiated on Oesclim 25, who can be satisfactorily maintained on
      this low dose after two months. STUDY DESIGN AND PATIENTS: This was an open
      label, multicentre, non-comparative, four-month treatment study. Treatment was
      initiated with Oesclim 25 (17 beta-oestradiol transdermal patch, 25 mcg/day).
      Dosage could be increased to Oesclim 50 if required after two months, according
      to clinical evaluation. Sequential treatment with an oral progestagen was also
      given for > or = 12 days/month in all non-hysterectomised women. A total of 1465
      women were included in the study. RESULTS: 82.3% (CI: 80.1-84.4) of patients
      remained on Oesclim 25 across the whole study. The mean number of hot flushes was
      reduced similarly by 93% and 94% at month 4 in the Oesclim 25 group and Oesclim
      50 group, respectively. However, at month 2 the decrease in hot flushes and other
      menopausal symptoms was less marked until the dose was adjusted, in patients
      switching to Oesclim 50. In a global evaluation, 97.5% of the investigators and
      95.7% of the patients rated the overall efficacy of the treatment as good/very
      good. Overall, treatment initiated at a low dose was well tolerated throughout
      the study, with a trend showing Oesclim 25 as being better tolerated than Oesclim
      50. CONCLUSION: Oesclim low dose (25 mcg) can effectively reduce symptoms in most
      postmenopausal women with a very satisfactory level of tolerability. The
      risk/benefit ratio observed is probably one key reason for good patient
      compliance.

PMID- 10893654
TI  - Dose response and safety of cizolirtine citrate (E-4018) in patients with pain
      following extraction of third molars.
AB  - The objectives of this study were to determine the dose response and safety of
      the oral analgesic cizolirtine citrate (E-4018) in patients with postoperative
      pain after third molar extraction. This was a placebo-controlled, double-blind,
      randomised, parallel-group study. Doses of E-4018 were 50 mg, 100 mg, or 150 mg.
      The primary outcome measure of efficacy was patient assessment of pain severity,
      determined from serial visual analogue scales (VAS) over a four-hour
      investigation period. Other efficacy measures included the number of patients
      taking escape analgesic and the time before it was taken, and an overall
      assessment of pain relief on a four-point categorical scale. There was no
      significant difference between any of the E-4018 treatment groups and placebo in
      terms of the AUC for VAS pain scores over time. The percentages of patients who
      took paracetamol within five hours of their dose were 100%, 95%, 78% and 82% for
      the placebo, 50 mg, 100 mg and 150 mg E-4018 groups, respectively. The time to
      first use of paracetamol was significantly different for the 100 mg and 150 mg E
      4018 groups compared to placebo. There were 17 adverse events, of which five were
      possibly related to the study medication (one in the placebo group and four in
      the 150 mg E-4018 group). We conclude that there was a dose-related trend in the
      percentage of patients requiring paracetamol within five hours of their study
      medication, and in the percentage of patients that recorded the treatment as
      providing good or excellent treatment of pain. There was, however, no firm
      evidence of a dose-related analgesic effect over the dose range of Cizolirtine
      chosen for this study. E-4018 was well tolerated in all patients.

PMID- 10893655
TI  - Comparison of the pharmacokinetic profiles of soluble aspirin and solid
      paracetamol tablets in fed and fasted volunteers.
AB  - The aim of this study was to investigate the absorption of popular preparations
      of two common analgesics--soluble aspirin and solid paracetamol tablets. An open,
      randomised, crossover study design was used to compare the pharmacokinetic
      parameters of soluble aspirin and solid paracetamol tablets in 16 healthy, male
      volunteers from the University of the Witwatersrand, South Africa, in both fed
      and fasted states. Plasma concentrations of paracetamol, aspirin and salicylic
      acid were measured. It was found that the rate of absorption was significantly
      faster for soluble aspirin than for solid paracetamol, regardless of fed or
      fasting state, considering time to maximum concentration (p < 0.01), time to
      first quantifiable concentrations (p < 0.05) and absorption rate (p < 0.01).
      Absorption rate was significantly affected by food for both soluble aspirin (p =
      0.028) and for solid paracetamol (p = 0.0003). Time to maximum concentration was
      not significantly affected by food for soluble aspirin (p = 0.17) but
      significantly lengthened for solid paracetamol (p = 0.0003). The extent of
      absorption was affected by food in terms of maximum concentration for both drugs
      (p = 0.0001), with a reduction of 49% in the fed state for solid paracetamol
      compared to 18% for soluble aspirin, the difference between the drugs being
      statistically significant (p = 0.0024). The overall bioavailability of soluble
      aspirin was unaffected by food and the bioavailability of salicylic acid was
      increased in the fed state, whereas that of solid paracetamol was lowered in the
      fed state. Greater inter-individual variation was seen in paracetamol
      concentrations compared with aspirin or salicylic acid levels. In conclusion,
      these results show that the absorption of soluble aspirin is largely unaffected
      by food, whereas, in the same volunteers, the absorption of solid paracetamol
      tablets is greatly affected. In some volunteers, maximum plasma concentrations of
      paracetamol following food did not reach levels previously reported to be
      required for effective analgesia, and this may have implications for pain relief
      in some individuals. The practice in some individuals of taking aspirin tablets
      after food to minimise potential gastric disturbance should not affect the level
      of analgesia.

PMID- 10893656
TI  - Patient acceptability of a new 3.0 ml pre-filled insulin pen.
AB  - The objective of these two studies was to assess patient acceptance and feature
      preferences of the new Lilly 3.0 ml pre-filled pen. A total of 701 patients with
      diabetes mellitus, who required insulin, were treated for 4-6 weeks with the pre
      filled pen. Patient acceptance and treatment preferences were assessed by a
      questionnaire completed at the end of the study period. Patients with type 1 or
      type 2 diabetes mellitus from South Africa (n = 371) and Croatia (n = 330) were
      enrolled in the study. The mean age was 51.6 years (range: 18-81), and gender was
      359 males and 342 females. Prior to the study, patients in South Africa (SA) had
      used the Novo Actraphane (Novo Nordisk, Bagsvaerd, Denmark) pen set, and patients
      in Croatia (C) had used NovoPen 1 or 2 (Novo Nordisk, Bagsvaerd, Denmark)
      (38.8%), NovoPen 3 (Novo Nordisk, Bagsvaerd, Denmark) (28.8%), B-D Pen (Becton
      Dickinson, Franklin Lakes, New Jersey, USA) (18.8%), needle/syringe (10.0%), oral
      hypoglycaemic agents (2.1%), or unknown (1.5%). The new Lilly 3.0 ml pre-filled
      pen features that were rated by respondents as good to excellent on a five-point
      rating scale included: cartridge visibility (C = 94%, SA = 83%), ease of dose
      correction (C = 92%, SA = 85%), dialling of the dose (C = 89%, SA = 81%), turning
      of the dose knob (C = 84%, SA = 82%) and attaching needles (C = 92%, SA = 78%).
      Most respondents (C = 78%, SA = 75%) preferred single-unit versus two-unit dosage
      increments. Overall, 76% of patients in Croatia and 80% in South Africa preferred
      the Lilly 3.0 ml pre-filled pen to their previous delivery device; 84% and 87% of
      patients, respectively, would recommend the pen to another patient. Also, the
      majority of patients in both trials rated the new Lilly 3.0 ml pre-filled pen as
      being more convenient and easier to use, and indicated that it represented a
      significant or modest improvement over their previous insulin injection method.
      The results of this study confirm that the new Lilly 3.0 ml pre-filled pen is
      widely accepted and preferred by patients using both reusable and pre-filled
      devices.

PMID- 10893657
TI  - A new formulation of fenofibrate: suprabioavailable tablets.
AB  - The rationale for, and development of, a new suprabioavailable fenofibrate tablet
      formulation is described. The new suprabioavailable tablet formulation combines
      well-established micronisation technology with a new micro-coating process. The
      new formulation provides more predictable and reliable drug absorption. Owing to
      the strong relationship between the fenofibrate dissolution performance and its
      oral bioavailability, equivalent plasma levels of active principal are achieved
      at a lower dose, with less inter-subject variability and a reduced food effect.
      The new suprabioavailable tablet may, therefore, be a more efficient and better
      tolerated formulation.

PMID- 10893658
TI  - HDL-cholesterol and the treatment of coronary heart disease: contrasting effects
      of atorvastatin and simvastatin.
AB  - Although the levels of low-density lipoprotein (LDL) cholesterol remain the main
      therapeutic goal when treating dyslipidaemias, there is a need to consider high
      density lipoprotein (HDL) concentrations. This conclusion is based on the
      findings of epidemiological surveys and appropriately designed trials using
      statins or fibrates. The importance of HDL, as a 'protective' lipoprotein
      fraction, has been recognised by major treatment guidelines. This review
      considers the differences in HDL-raising capacity of two of the most commonly
      prescribed statins--atorvastatin and simvastatin. When compared with simvastatin,
      atorvastatin is associated with progressively decreasing rises in the levels of
      HDL as the dose increases (negative dose response), an effect not reported with
      other statins. In contrast, simvastatin shows a positive dose response
      (increasing concentrations of HDL with increasing dose). This effect is
      paralleled by changes in apolipoprotein A-I levels. Apolipoprotein A-I is the
      main apolipoprotein associated with HDL. This dissimilarity in HDL response is an
      example of several differences that have been reported when comparing various
      statins. If 'all statins are not created equal', we should focus prescribing on
      those statins that have end point evidence originating from appropriately
      designed trials.

PMID- 10893659
TI  - Treating osteoarthritis in practice--the TOP Study.
AB  - This study consisted of two nationwide surveys. The first involved 209 general
      practitioners (GPs) from 22 sampling points in England, Scotland and Wales, and
      the second involved 510 patients with osteoarthritis (OA) (aged 60 years and
      above), rheumatoid arthritis (RA) or unspecified arthritis, who had visited their
      GP for treatment. The results showed that OA has a significant negative impact on
      patients' quality of life; 79% of patients stated that their condition limited
      their quality of life. Only 15% of GPs reported prescribing a conventional non
      steroidal anti-inflammatory drug (NSAID) as first-line treatment for patients
      with arthritis. More than half (57%) stated that they would prescribe a simple
      analgesic or a compound analgesic before trying an NSAID. Forty four per cent of
      GPs stated that their main therapeutic objective when prescribing an NSAID was to
      minimise GI side-effects, and therefore start at a low dose. This implies that
      many patients are likely to be receiving sub-optimal doses. Experiencing
      breakthrough pain and GI side-effects were common reasons cited for patients re
      presenting to GPs. GPs reported their expectation to prescribe GI protectants to
      a fifth (21%) of their patients on NSAIDs and estimated one in six patients (17%)
      take OTC products to relieve GI symptoms. This research demonstrates that there
      is considerable dissatisfaction with currently used treatment regimens for
      osteoarthritis, from both the GP and patient perspectives.

PMID- 10893660
TI  - Psychological assessment in XLMR: a proposal for setting international standards.
AB  - The need for an agreed upon set of standards for assessing individuals with XLMR
      was made quite evident this past year at the Fragile X and XLMR Workshop in
      Strasbourg. Several affected individuals from different families may have been
      incorrectly diagnosed as MR. Many factors can have a negative affect on IQ
      testing. As a result, evaluating individuals with cognitive deficits can be
      problematic. To be effective, psychological assessments must produce uniform
      results that are consistent with the definition of MR. Therefore, to foster
      international research in XLMR. I propose a two-stage standardized protocol. To
      determine which tests may be suitable. I review an assortment of instruments for
      psychological assessment at each stage, noting their strengths and weaknesses.
      Afterward, I present a set of standardized protocols based on age and language
      ability.

PMID- 10893661
TI  - Three young children with Smith-Magenis syndrome: their distinct, recognisable
      behavioural phenotype as the most important clinical symptoms.
AB  - We report on the development and behaviour of three young children with Smith
      Magenis syndrome (SMS), del 17p11.2. The behaviour problems and the psychomotor
      delay in preschool children with SMS are often more striking than the dysmorphic
      features and can serve as a useful clue to the diagnosis. We compare the
      behaviour with reported data. The behaviour problems in the three four year olds
      include very demanding behaviour, severe temper tantrums, hyperactivity,
      aggressive behaviour, self injurious behaviour, sleeping problems and stereotypic
      behaviour. Head banging, hand, wrist or finger biting are present.
      Onychotyllomania is not observed. Insertion of objects in the mouth as well as
      excessive nose picking is very frequent, although polyembolokoilomania is not
      present. The so called self hug when excited is present in one child. The
      behaviour problems and psychomotor delay represent a major management problem for
      the parents.

PMID- 10893662
TI  - Marden-Walker syndrome: case report, nosologic discussion and aspects of
      counseling.
AB  - The Marden-Walker syndrome is characterized by a mask-like face with
      blepharophimosis, micrognathia, cleft or high-arched palate, low-set ears,
      congenital joint contractures, decreased muscular mass, failure to thrive and
      psychomotor retardation. We report a boy with a phenotype mostly resembling the
      condition named Marden-Walker syndrome, with many of the criteria proposed for
      diagnosing this particular phenotype. In addition he had hypoplastic corpus
      callosum, cerebellar vermis hypoplasia, enlarged cisterna magna and vertebral
      abnormalities. During pregnancy there were reduced fetal movements. In the
      present patient the fetal hypokinesia sequence, due to central nervous system
      malformation, is most compatible with the diagnosis of Marden-Walker syndrome.
      The etiology is probably heterogeneous, but the possibility of autosomal
      recessive inheritance should be considered in genetic counseling.

PMID- 10893663
TI  - Pure distal monosomy 10q26 in a patient displaying clinical features of Prader
      Willi syndrome during infancy and distinct behavioural phenotype in adolescence.
AB  - A male patient is reported with terminal 10q26 deletion and clinical findings
      suggesting Prader-Willi syndrome during the infancy. These findings included
      decreased fetal movements, neonatal hypotonia, need for tube feeding,
      characteristic facial dysmorphism with dolichocephaly, narrow bifrontal diameter,
      almond-shaped eyes and epicanthus, hypogenitalism and developmental retardation.
      However, during the further evolution there was neither hyperphagia nor obesity
      and chromosomal and molecular investigations failed to confirm the diagnosis of
      Prader-Willi syndrome. Special behavioural abnormalities became evident with
      notably hyperactivity, hyperkinesis and destructive tendency. Finally, at the age
      of 17 years high resolution chromosome studies revealed a terminal 10q26.3
      deletion. A review of the literature is made on previously reported patients with
      either a Prader-Willi-like syndrome or a terminal 10q deletion with behavioural
      problems.

PMID- 10893664
TI  - Simultaneous interdisciplinary counseling in German breast/ovarian cancer
      families: first experiences with patient perceptions, surveillance behavior and
      acceptance of genetic testing.
AB  - As part of a multicenter study supported by the German Mildred Scheel foundation
      we have established an interdisciplinary counseling setting for members of breast
      and/or ovarian cancer families. We offer simultaneous counseling by a team
      consisting of a geneticist, a gynecologist and a psycho-oncologist. Here we
      describe our counseling protocol and our first short-term experience with this
      interdisciplinary approach. Preliminary data on patient perceptions and behaviors
      in the context of DNA testing are reported. Overall, our counseling approach was
      perceived as beneficial both by the counselors and the consultants. A marked
      overestimation of the risk to develop breast and/or ovarian cancer was noted in
      the group of unaffected individuals from medium to low risk breast cancer
      families in contrast to an appropriate risk perception in members from high risk
      families. All participants shared many of the same expectations about genetic
      testing and counseling and appeared to base their decision-making about testing
      on the risk classification given by the genetic counselor. The reported
      participation in gynecological cancer prevention programs was high in all
      families at risk, but was less sufficient in unaffected as compared to affected
      persons. Although current data on BRCA1/BRCA2 mutation analyses render testing in
      medium to low risk individuals questionable, our findings emphasize the
      importance of genetic counseling and education in all risk categories of breast
      and/or ovarian cancer families.

PMID- 10893665
TI  - Lenz microphthalmia syndrome: three additional cases with rare associated
      anomalies.
AB  - Lenz microphthalmia syndrome is an extremely rare inherited disorder,
      characterized by unilateral or bilateral microphthalmia. In rare cases affected
      patients exhibit complete absence of eye or blepharoptosis resulting in visual
      impairment. Additional physical abnormalities are often associated with this
      disorder, orofacial, digital, skeletal and urogenital abnormalities. Here we
      present three cases of Lenz microphthalmia with additional manifestations: two
      brothers of first cousin mating, the elder one has bilateral congenital cataract
      which is a rare ophthalmological finding in this syndrome and a third case who
      presented to us because of ambiguous genitalia. She was 12 years old, and reared
      as a female. Chromosomal analysis showed 46,XY karyotype, and hormonal studies
      indicated 5-alpha reductase deficiency. This is the first report of the
      association of 5-alpha reductase deficiency with Lenz microphthalmia syndrome.

PMID- 10893666
TI  - Branchial cleft anomaly, congenital heart disease, and biliary atresia: Goldenhar
      complex or Lambert syndrome?
AB  - The features of Goldenhar complex have been well-described and classically
      include branchial arch abnormalities, epibulbar dermoid and vertebral
      abnormalities. We have identified an infant with these features in association
      with complex congenital heart disease and intrahepatic biliary atresia. Although
      Lambert described an autosomal recessive disorder with an association of biliary
      atresia and branchial arch abnormalities, none of those cases had epibulbar
      dermoid. Diagnostic considerations in this case include inclusion of biliary
      atresia as a new feature in the expanding spectrum of the Goldenhar complex,
      versus Lambert syndrome with epibulbar dermoid.

PMID- 10893667
TI  - Osteopathia striata with cranial sclerosis: literature reappraisal argues for X
      linked inheritance.
AB  - Osteopathia striata with cranial sclerosis (OS-CS) is characterized by linear
      striations of tubular bones and fan-shaped configurations of the ilia. Although
      referred in literature as an autosomal dominant disorder the clinical pattern of
      partial involvement as well as the reported family observations plead for X
      linked inheritance with mild striated bone affections in carrier women and severe
      syndromic morbidity and high mortality in the males. Sporadic affected males are
      probably somatic mosaics. There is no proven father-son transmission. Symptomatic
      osteopathia striata (OS) is characteristic in X-linked focal dermal hypoplasia
      Goltz-Gorlin.

PMID- 10893668
TI  - An uncommon G375C substitution in a newborn with achondroplasia.
AB  - We report a G-to-T de novo transversion mutation causing the substitution of a
      glycine with a cysteine (G375C) in a newborn with achondroplasia. This rare
      observation confirms allelic heterogeneity.

PMID- 10893669
TI  - Four new DNA variants in the NF1 coding region.

PMID- 10893670
TI  - Maternal pericentric inversion in the origin of an abnormal child due to a
      recombinant chromosome 1--implications for genetic counseling.

PMID- 10893671
TI  - Diaphragmatic hernia and Fryns syndrome phenotype in partial trisomy 22.

PMID- 10893672
TI  - Genetic determination of Colles' fracture and differential bone mass in women
      with and without Colles' fracture.
AB  - Osteoporotic fractures (OFs) are a major public health problem. Direct evidence
      of the importance and, particularly, the magnitude of genetic determination of OF
      per se is essentially nonexistent. Colles' fractures (CFs) are a common type of
      OF. In a metropolitan white female population in the midwestern United States, we
      found significant genetic determination of CF. The prevalence (K) of CF is,
      respectively, 11.8% (+/- SE 0.7%) in 2471 proband women aged 65.55 years (0.21),
      4.4% (0.3%) in 3803 sisters of the probands, and 14.6% (0.7%) in their mothers.
      The recurrence risk (K0), the probability that a woman will suffer CF if her
      mother has suffered CF is 0.155 (0.017). The recurrence risk (Ks), the
      probability that a sister of a proband woman will suffer CF given that her
      proband sister has suffered CF is 0.084 (0.012). The relative risk lambda (the
      ratio of the recurrence risk to K), which measures the degree of genetic
      determination of complex diseases such as CF, is 1.312 (0.145; lambda 0) for a
      woman with an affected mother and 1.885 (0.276; lambda s) for a woman with an
      affected sister. A lambda-value significantly greater than 1.0 indicates genetic
      determination of CF. The terms lambda 0 and lambda s are related to the genetic
      variances of CF. These parameters translate into a significant and moderately
      high heritability (0.254 [0.118]) for CF. These parameters were estimated by a
      maximum likelihood method that we developed, which provides a general tool for
      characterizing genetic determination of complex diseases. In addition, we found
      that women without CF had significantly higher bone mass (adjusted for important
      covariates such as age, weight, etc.) than women with CF.

PMID- 10893673
TI  - Genetics of fracture: challenges and opportunities.

PMID- 10893674
TI  - Collagenase-3 (MMP-13) and integral membrane protein 2a (Itm2a) are marker genes
      of chondrogenic/osteoblastic cells in bone formation: sequential temporal, and
      spatial expression of Itm2a, alkaline phosphatase, MMP-13, and osteocalcin in the
      mouse.
AB  - Endochondral bone formation requires the action of cells of the chondrocytic and
      osteoblastic lineage, which undergo continuous differentiation during this
      process. To identify subpopulations of resting, proliferating, and hypertrophic
      chondrocytes and osteoblasts involved in bone formation, we have identified here
      two novel marker genes present in endochondral and intramembranous ossification.
      Using Northern blot analysis and in situ hybridization on parallel sections of
      murine embryos and bones of newborn mice we compared the expression pattern of
      the recently cloned Itm2a and MMP-13 (collagenase-3) genes with that of
      established marker genes for bone formation, such as alkaline phosphatase (ALP),
      osteocalcin (OC), and collagen type X, during endochondral and intramembranous
      ossification. During embryonic development expression of Itm2a and ALP was
      detectable at midgestation (11.5 days postcoitum [dpc]) and increased up to 16.5
      dpc. MMP-13 and OC expression started at 14.5 dpc and 16.5 dpc, respectively.
      This temporal expression was reflected in the spatial distribution of these
      markers in the growth plate of long bones. In areas undergoing endochondral
      ossification Itm2a expression was found in chondrocytes of the resting and the
      proliferating zones. Expression of ALP and MMP-13 are mutually exclusive: ALP
      transcripts were found only in collagen type X positive hypertrophic chondrocytes
      of the upper zone. MMP-13 expression was restricted to chondrocytes of the lower
      zone of hypertrophic cartilage also expressing collagen type X. In osteoblasts
      involved in endochondral and intramembranous ossification Itm2a was not present.
      ALP, MMP-13, and OC were mutually exclusively expressed in these cells suggesting
      a differentiation-dependent sequential expression of ALP, MMP-13, and OC. The
      identification of the continuum of sequential expression of Itm2a, ALP, MMP-13,
      and OC will now allow us to establish a series of marker genes that are highly
      suitable to characterize bone cells during chondrocytic and osteoblastic
      differentiation in vivo.

PMID- 10893675
TI  - Cellular localization of neprilysin in mouse bone tissue and putative role in
      hydrolysis of osteogenic peptides.
AB  - The regulation of osteoblast and osteoclast metabolism is mediated by both
      hormones and local bone peptide factors. Peptides and hormones are under control
      of membrane peptidases such as Neprilysin (NEP). NEP is a widely distributed cell
      surface zinc-metallopeptidase that is involved in the regulation of several
      important physiological processes by controlling the half-life of bioactive
      peptides. Although NEP is known to be present in skeletal tissues, neither its
      cellular localization nor its function have been established. To address this
      question, we examined NEP distribution in bones of postnatal mouse. In situ
      hybridization (ISH) and immunohistochemistry showed that NEP messenger RNA (mRNA)
      and protein are associated with bone-forming cells including presumptive
      osteoblast precursors, preosteoblasts, osteoblasts, and osteocytes. NEP levels in
      newborn and adult mice bones also were compared by immunoblotting. Higher amounts
      of NEP immunoreactivity were observed in newborn as compared with adult bones,
      suggesting a relationship between NEP expression and bone growth. To further
      explore this hypothesis, we monitored in vitro NEP proteolytic activity using a
      series of synthetic osteogenic peptides such as parathyroid hormone-related
      peptide 1-43 (PTHrP1-34), osteostatin (PTHrP107-139), osteogenic growth peptide
      (OGP), calcitonin, alpha-calcitonin gene-related peptide (alpha-CGRP), and PTH1
      34. Except for PTH1-34, all peptides were found to be NEP substrates.

PMID- 10893676
TI  - Cardiac L-type calcium channel alpha 1-subunit is increased by cyclic adenosine
      monophosphate: messenger RNA and protein expression in intact bone.
AB  - L-type calcium channels have been identified previously in both osteoblast-like
      osteosarcoma cell lines and primary cultures of osteoblasts using numerous
      techniques such as patch clamp recording, drug inhibited 45Ca2+ uptake, and Fura
      2 measurements, but intact bone has not been investigated. Using reverse
      transcription polymerase chain reaction (RT-PCR) we found that the three major
      isoforms of the alpha 1-subunit of L-type calcium channels, (alpha 1C, alpha 1D,
      and alpha 1S) are present in RNA extracted from ROS 17/2.8 osteosarcoma cells,
      rat femur, and rat skull. Sequencing of most of the alpha 1C-subunit from rat
      femur and ROS cells revealed that the splice variants in osteosarcoma cells and
      intact bone differ, but there are no unique sequence variations compared with
      those found in other tissues. Northern blot analysis of ROS cell RNA indicated
      that cyclic adenosine monophosphate (cAMP), but not 1 alpha, 25-dihydroxyvitamin
      D3, increased the messenger RNA (mRNA) of the alpha 1C-subunit. Western blot of
      ROS cell lysates revealed a band of more then 220 kDa, the amount of which
      increased in cells treated with cAMP. Using confocal microscopy combined with
      immunohistochemistry in ROS cells, intact bone, and cartilage, we found that the
      alpha 1C-subunit of this channel is expressed in osteoblasts and chondrocytes
      suggesting this channel may be a pathway for signal transduction in intact
      tissue, because it is in osteosarcoma cell lines and primary osteoblasts grown in
      tissue culture.

PMID- 10893677
TI  - The monoclonal antibodies 18d7/91f2 recognize a receptor regulatory protein on
      mouse bone marrow stromal cells.
AB  - Two monoclonal antibodies 18D7 and 91F2 were developed by immunizing rats with
      the mouse bone marrow-derived osteogenic cell line MN7. Hybridomas secreting rat
      antibodies against MN7 cell surface markers were selected by flow cytometry
      analysis. Both the monoclonal antibody 18D7 and the monoclonal antibody 91F2 are
      directed against the same cell surface antigen present on MN7 cells. Here, we
      report on the immunopurification of the 18D7/91F2 antigen and its identification
      as the prostaglandin F2 alpha receptor regulatory protein (FPRP). FPRP is
      expressed as a single messenger RNA (mRNA) of approximately 6 kilobases (kb) in
      MN7 cells and is differentially expressed in developing osteogenic cultures of
      bone marrow cells of the mouse. However, addition of the monoclonal antibodies
      18D7 and 91F2 to these cultures did not inhibit bone formation in vitro. Both
      monoclonal antibodies reacted with mouse stromal cell lines established from bone
      marrow, thymus, spleen, and mandibular condyles. Immunohistochemical analysis of
      mature tibia of mice using the monoclonal antibody 18D7 revealed the presence of
      a distinct population of bone marrow cells close to trabecular and endosteal bone
      surfaces. In the central bone marrow, hardly any positive cells were found. In 17
      day-old fetal mouse radius 18D7 immunoreactivity was restricted to cells in the
      periosteum in close vicinity to the bone collar. Mature osteoblasts, osteoclasts,
      osteocytes, growth plate chondrocytes, and mature macrophages were all negative.
      Taken together, these results suggest that FPRP plays a role in the osteogenic
      differentiation process.

PMID- 10893678
TI  - Structure, composition, and maturation of newly deposited calcium-phosphate
      crystals in chicken osteoblast cell cultures.
AB  - Characterization of the very early calcium phosphate (CaP) crystals deposited in
      bone or in osteoblast cell cultures has been hampered by the overwhelming
      presence of organic matrix components and cells that obscure spectral analyses.
      We have overcome this problem using isolated protein-free crystals and have
      obtained new data including 31P nuclear magnetic resonance (NMR) spectra for the
      first time from mineral crystals deposited during osteoblast calcification in
      culture. Crystals were isolated from cultures at two time points: (a) at first
      calcium accumulation (day 8-10) and (b) after 60 days of culture, to assess
      maturational changes. The analyses show that the chemical composition overall and
      short range order of the early and mature crystals are characteristic of the
      apatite crystals found in young embryonic chick bone in vivo. No mineral phase
      other than apatite was detected by any of the methods used. 31P NMR spectroscopy
      identified the HPO4 groups as those present in bone apatite. Similar to bone
      apatites, no OH groups were detected by Fourier transform infrared (FTIR)
      spectroscopy. The temporal maturational changes in composition and structure of
      the mineral phase were difficult to assess because of the continuous deposition
      of crystals throughout culturing. The pathway of the maturational changes
      observed were similar to those occurring in chick bone in vivo and synthetic
      apatite crystals in vitro although to a much smaller extent.

PMID- 10893679
TI  - Spaceflight inhibits bone formation independent of corticosteroid status in
      growing rats.
AB  - Bone formation and structure have been shown repeatedly to be altered after
      spaceflight. However, it is not known whether these changes are related to a
      stress-related altered status of the corticosteroid axis. We investigated the
      role of corticosteroids on spaceflight-induced effects in rat pelvis and thoracic
      vertebrae. Thirty-six male Sprague-Dawley rats were assigned to a flight, flight
      control, or vivarium group (n = 12/group). Bilateral adrenalectomy was performed
      in six rats per group, the additional six rats undergoing sham surgery.
      Adrenalectomized (ADX) rats were implanted with corticosteroid pellets. On
      recovery from spaceflight, thoracic vertebrae and the whole pelvis were removed
      and processed for biochemistry, histomorphometry, or bone cell culture studies.
      The 17-day spaceflight resulted in decreased bone volume (BV) in the cotyle area
      of pelvic bones (-12%; p < 0.05) associated with approximately 50% inhibition of
      bone formation in the cancellous area of pelvic metaphyses and in thoracic
      vertebral bodies. The latter effect was associated with a decreased number of
      endosteal bone cells isolated from the bone surface (BS) in these samples (-42%;
      p < 0.05). This also was associated with a decreased number of alkaline
      phosphatase positive (ALP+) endosteal bone cells at 2 days and 4 days of culture,
      indicating decreased osteoblast precursor cell recruitment. Maintaining basal
      serum corticosterone levels in flight-ADX rats did not counteract the impaired
      bone formation in vertebral or pelvic bones. Moreover, the decreased ex vivo
      number of total and ALP+ endosteal bone cells induced by spaceflight occurred
      independent of endogenous corticosteroid hormone levels. These results indicate
      that the microgravity-induced inhibition of bone formation and resulting
      decreased trabecular bone mass in specific areas of weight-bearing skeleton in
      growing rats occur independently of endogenous glucocorticoid secretion.

PMID- 10893680
TI  - Prostaglandin E2 induces expression of receptor activator of nuclear factor-kappa
      B ligand/osteoprotegrin ligand on pre-B cells: implications for accelerated
      osteoclastogenesis in estrogen deficiency.
AB  - Estrogen deficiency causes bone loss as a result of accelerated osteoclastic bone
      resorption. It also has been reported that estrogen deficiency is associated with
      an increase in the number of pre-B cells in mouse bone marrow. The present study
      was undertaken to clarify the role of altered B lymphopoiesis and of the receptor
      activator of nuclear factor-kappa B ligand (RANKL), a key molecule in
      osteoclastogenesis, in the bone loss associated with estrogen deficiency. In the
      presence of prostaglandin E2 (PGE2), the activity to form tartrate-resistant acid
      phosphatase (TRAP)-positive osteoclast-like cells was significantly greater in
      bone marrow cells derived from ovariectomized (OVX) mice than in those from sham
      operated mice. Northern blot analysis revealed that PGE2 increased the amount of
      RANKL messenger RNA (mRNA) in bone marrow cells, not only adherent stromal cells
      but nonadherent hematopoietic cells; among the latter, RANKL mRNA was more
      abundant in OVX mice than in shamoperated mice and was localized predominantly in
      B220+ cells. Flow cytometry revealed that most B220+ cells in bone marrow were
      RANKL positive and that the percentage of RANKL-positive, B220low cells was
      higher in bone marrow from OVX mice than in that from sham-operated mice. The
      increase in the expression of RANKL and the percentage of these cells in OVX mice
      was abolished by the administration of indomethacin in vivo. PGE2 also markedly
      increased both the level of RANKL mRNA and cell surface expression of RANKL
      protein in the mouse pre-B cell line 70Z/3. Finally, osteoclastogenic response to
      PGE2 was reduced markedly by prior depletion of B220+ cells, and it was restored
      by adding back B220+ cells. Taken together with stimulated cyclo-oxygenase (COX)
      2 activity by tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) in
      estrogen deficiency, these results suggest that an increase in the number of
      B220+ cells in bone marrow may play an important role in accelerated bone
      resorption in estrogen deficiency because B220+ cells exhibit RANKL on the cell
      surface in the presence of PGE2, thereby leading to accelerated
      osteoclastogenesis.

PMID- 10893681
TI  - Pyridinium cross-links in bone of patients with osteogenesis imperfecta: evidence
      of a normal intrafibrillar collagen packing.
AB  - The brittleness of bone in patients with osteogenesis imperfecta (OI) has been
      attributed to an aberrant collagen network. However, the role of collagen in the
      loss of tissue integrity has not been well established. To gain an insight into
      the biochemistry and structure of the collagen network, the cross-links
      hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) and the level of triple
      helical hydroxylysine (Hyl) were determined in bone of OI patients (types I, III,
      and IV) as well as controls. The amount of triple helical Hyl was increased in
      all patients. LP levels in OI were not significantly different; in contrast, the
      amount of HP (and as a consequence the HP/LP ratio and the total pyridinoline
      level) was significantly increased. There was no relationship between the sum of
      pyridinolines and the amount of triple helical Hyl, indicating that lysyl
      hydroxylation of the triple helix and the telopeptides are under separate
      control. Cross-linking is the result of a specific three-dimensional arrangement
      of collagens within the fibril; only molecules that are correctly aligned are
      able to form cross-links. Inasmuch as the total amount of pyridinoline cross
      links in OI bone is similar to control bone, the packing geometry of
      intrafibrillar collagen molecules is not disturbed in OI. Consequently, the
      brittleness of bone is not caused by a disorganized intrafibrillar collagen
      packing and/or loss of cross-links. This is an unexpected finding, because mutant
      collagen molecules with a random distribution within the fibril are expected to
      result in disruptions of the alignment of neighboring collagen molecules. Pepsin
      digestion of OI bone revealed that collagen located at the surface of the fibril
      had lower cross-link levels compared with collagen located at the inside of the
      fibril, indicating that mutant molecules are not distributed randomly within the
      fibril but are located preferentially at the surface of the fibril.

PMID- 10893682
TI  - Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption.
AB  - Human serum contains two forms of tartrate-resistant acid phosphatase (TRAP), 5a
      and 5b. Of these, 5a contains sialic acid and 5b does not. We show here that
      antigenic properties and pH optimum of TRAP purified from human osteoclasts are
      identical to those of serum TRAP 5b and completely different from those of serum
      TRAP 5a, suggesting that 5b would be derived from osteoclasts and 5a from some
      other source. We developed a novel immunoassay specific for 5b using a monoclonal
      antibody O1A as capture antibody. O1A did not bind acid phosphatase derived from
      platelets and erythrocytes. Western analysis showed that O1A was specific for
      TRAP in both human bone and serum. We measured bound TRAP activity at pH 6.1,
      where 5b is highly active and 5a almost completely inactive. The immunoassay
      detected more than 90% of the initial TRAP 5b activity after 8-h incubation of
      serum samples at 25 degrees C and after 3 days incubation at 4 degrees C. Serum
      TRAP 5b activity decreased significantly after 6 months of hormone replacement
      therapy (HRT) of postmenopausal women compared with the change observed in
      postmenopausal women receiving placebo (p < 0.0001). Instead, no significant
      differences were observed between the changes in the placebo and HRT groups in
      total serum TRAP amount. These results show that serum TRAP 5b is a specific and
      sensitive marker for monitoring antiresorptive treatment. Instead, total serum
      TRAP cannot be used for that purpose. These findings may turn out to be a
      significant improvement in using serum TRAP as a resorption marker.

PMID- 10893683
TI  - An in vivo model for investigations of mechanical signal transduction in
      trabecular bone.
AB  - The premise that bone cells are able to perceive and respond to mechanical forces
      is well accepted. This article describes the use of an in vivo hydraulic bone
      chamber for investigations of mechanical signal transduction. The servohydraulic
      loading mechanism was activated to apply a controlled compressive load to the
      woven trabecular bone that formed in one chamber, while the contralateral chamber
      served as an unloaded control. Specimens were harvested at a series of postload
      time points, and the cellular response to loading was evaluated by cytochemical,
      histomorphometric, and Northern blot analysis. A repetitive daily load stimulus
      elicited osteoblast biosynthetic activity characterized by an initial increase in
      type I procollagen by day 3 and a subsequent rise in alkaline phosphatase (ALP)
      activity after the sixth daily load episode. Application of a single load episode
      induced a biphasic pattern of c-fos and zif-268 gene expression with up
      regulation at 30 minutes, down-regulation at 12 h, and up-regulation 24 h after
      the mechanical stimulus. The results show that a synchronized pattern of bone
      cell activity and gene expression occurs in response to controlled mechanical
      stimulation and that candidate load-responsive molecular mediators can be
      evaluated easily by this model.

PMID- 10893684
TI  - Sympathectomy, which induces membranous bone remodeling, has no effect on
      endochondral long bone remodeling in vivo.
AB  - Sympathectomy has been shown to induce resorption within the membranous middle
      ear bone of gerbils. It is unknown whether sympathectomy exerts a similar effect
      on endochondral long bone. In the present study, guanethidine sulfate (GS) and 6
      hydroxydopamine (HDA) were administered to gerbils to induce sympathectomy. One
      week later, samples of middle ear bulla bone and radial long bone were harvested
      and assessed for osteoclastic activity. Histomorphometric analysis showed both
      pharmacologic sympathectomy with GS and chemical sympathectomy with HDA
      significantly increased the osteoclast counts and osteoclast surfaces of bulla
      bone samples but not radial long bone samples, respectively. In contrast, HDA but
      not GS increased the osteoclast profile area of both long bone and membranous
      bone samples when compared with vehicle-treated controls. Sympathectomy, induced
      both chemically and pharmacologically, thus has been shown to increase resorption
      in membranous bone but not endochondral long bone in the gerbilline model.

PMID- 10893685
TI  - Estrogen agonist (zeranol) treatment in a castrated male lamb model: effects on
      growth and bone mineral accretion.
AB  - The mechanism of estrogen's action on bone mineralization in children has
      received little attention. Our objective was to determine the effect of time
      (developmentally) and duration of exposure to an estrogen agonist (zeranol) on
      bone growth and mineralization using a castrated male lamb model. At birth, 40
      male lambs were castrated and within 14 days of birth (day = 0) they were
      assigned (n = 10 per group) to age-matched control lambs (C-AGE) or to receive a
      12.5-mg zeranol implant as follows: E-0, implanted on days 0, 45, 90, and 135; E
      90, implanted on days 90 and 135; and E-0, 90, implanted on days 0, 90, and 135.
      Lambs were studied for 163 days. Serum was collected on days 28, 73, 118, 135,
      and 163 and analyzed for minerals (Ca, P, and Mg), markers of bone remodeling
      (bone alkaline phosphatase [ALP] and tartrate resistant acid phosphatase [TRAP]),
      1,25-dihydroxyvitamin D [1,25(OH)2D], growth hormone (GH), and insulin-like
      growth factor I (IGF-I). Whole-body bone mineral content (BMC), bone mineral
      density (BMD), fat mass, and lean mass were determined by dual energy X-ray
      absorptiometry (DEXA) on days 28, 73, 118, and 163. There was a linear increase
      in growth at all time points. Whole-body BMC, weight, and lean mass of C-AGE and
      E-90 lambs were less than E-0, and E-0, 90 lambs at all time points. Whole-body
      BMD of C-AGE and E-90 lambs was less than E-0 and E-0, 90 lambs at 28 days and 73
      days; however, after implantation at day 90 whole-body BMD of E-90 lambs was
      similar to E-0 and E-0, 90 lambs at day 118 and day 163 and all three were
      greater than C-AGE lambs. There was no effect of treatment on calcium absorption,
      serum minerals, hormones, or markers of bone remodeling. We conclude from these
      data that treatment of growing castrated lambs with an estrogen agonist from
      birth augments growth, whereas delaying estrogen agonist treatment does not
      facilitate growth but appears to augment bone mineral accretion. We suggest these
      observations may have clinical relevance, and deserve consideration when treating
      children with delays in growth and bone mineral accretion.

PMID- 10893686
TI  - Bone structure in patients with low bone mineral density with or without
      vertebral fractures.
AB  - Vertebral fractures (VFX) are caused by low bone mass and microstructural
      deterioration of bone tissue. The latter is not well defined. We investigated
      bone structure in transiliac biopsy specimens from 88 volunteers. Biopsy
      specimens were obtained at baseline in the Multiple Outcomes of Raloxifene
      Evaluation trail, a prospective study in osteoporotic (BMD < or = -2.5 T score)
      postmenopausal women without or with VFX on standardized lateral spinal
      radiographs. Bone biopsy specimens were embedded in methylmethacrylate (MMA).
      Histomorphometry was done in 8 microns (U.S.A.) or 5 microns (Europe) Goldner
      stained sections. Vertebral fracture status (yes/no) was the outcome variable in
      logistic regression models adjusted for age and biopsy specimen origin (U.S.A.
      vs. Europe). Patients with and without VFX (26/62) were similar regarding age
      (69.2 +/- 5.2 years vs. 67.3 +/- 6.7 years), bone volume (BV/TV; 17.7 +/- 4.7%
      vs. 19.0 +/- 5.8%), and bone surface (BS/TV; 2.7 +/- 0.6 mm2/mm3 vs. 2.8 +/- 0.6
      mm2/mm3). A lower cortical thickness (C.Th; 652 +/- 267 microns vs. 822 +/- 325
      microns), total strut length (TSL; 826 +/- 226 microns/mm2 vs. 922 +/- 256
      microns/mm2), node-to-loop (Nd-Lp) strut length (10.1 +/- 10.3% vs. 15.0 +/-
      13.6%), together with a higher node-to-terminus (Nd-Tm) strut length (45.6 +/-
      9.7% vs. 39.1 +/- 9.3%) were each associated with prevalent VFX (0.01 < p <
      0.10). Differences in BV/TV did not explain these associations. In conclusion,
      cortical thinning and disruption of trabecular lattice are possible pathogenic
      mechanisms in patients with VFX.

PMID- 10893687
TI  - Association of a polymorphism in the TNFR2 gene with low bone mineral density.
AB  - Previous genetic linkage data suggested that a gene on chromosome 1p36.2-36.3
      might be linked to low bone mineral density (BMD). Here, we examine the gene for
      tumor necrosis factor receptor 2 (TNFR2), a candidate gene within that interval,
      for association with low BMD in a group of 159 unrelated individuals. We assess
      two polymorphic sites within the gene, a microsatellite repeat within intron 4,
      and a three-nucleotide variation in the 3' untranslated region (UTR) of the gene.
      The latter has five alleles of which the rarest allele is associated with low
      spinal BMD Z score (p = 0.008). Lowest mean spinal BMD Z scores were observed for
      individuals having genotypes that were heterozygous for the rarest allele. No
      homozygotes for the rarest allele were observed. Preliminary analysis suggests
      that there is a difference in the genotype frequency distribution between the
      group with low BMD and a control group.

PMID- 10893688
TI  - Health-related quality of life in postmenopausal women with low BMD with or
      without prevalent vertebral fractures.
AB  - Fractures and subsequent morbidity determine the impact of established
      postmenopausal osteoporosis. Health-related quality of life (HRQOL) has become an
      important outcome criterion in the assessment and follow-up of osteoporotic
      patients. As part of the baseline measurements of the Multiple Outcomes of
      Raloxifene Evaluation (MORE) study, HRQOL was assessed in 751 osteoporotic (bone
      mineral density [BMD] T score > or = -2.5) women from Europe with or without
      vertebral fractures (VFX). This was done using the quality of life questionnaire
      of the European Foundation for Osteoporosis (QUALEFFO), Nottingham Health Profile
      (NHP) and the EQ-5D (former EuroQol). QUALEFFO contains questions in five
      domains: pain, physical function, social function, general health perception, and
      mental function. Each domain score and QUALEFFO total scores are expressed on a
      100-point scale, with 0 corresponding to the best HRQOL. In comparison with
      patients without VFX, those with VFX were older (66.2 +/- 5.9 years vs. 68.8 +/-
      6.3 years; p < 0.001), had higher prevalence of nonvertebral fractures (25% vs.
      36%; p = 0.002), and higher QUALEFFO scores (worse HRQOL; total score, 26 +/- 14
      vs. 36 +/- 17; p < 0.001). QUALEFFO scores increased progressively with
      increasing number of VFX, especially lumbar fractures (p < 0.001). Patients with
      a single VFX already had a significant increase in QUALEFFO scores (p < 0.05).
      Similar, though weaker, associations were seen for NHP and EQ-5D scores. This
      study confirms decreased HRQOL for patients with prevalent VFX. In osteoporotic
      patients, QUALEFFO scores change in relation to the number of VFX. QUALEFFO is
      suitable for clinical studies in patients with postmenopausal osteoporosis.

PMID- 10893689
TI  - Bone mineral in prepubertal children: gender and ethnicity.
AB  - Previous reports of gender and ethnic differences in bone mineral in prepubertal
      children have been inconsistent due to different methodologies, the problematic
      nature of bone density by dual-energy X-ray absorptiometry (DXA) calculated as
      the ratio of bone mineral mass to projected bone area (BA), and the generally
      small study populations. The aim of this study was to test the hypothesis that
      gender and ethnic differences in bone mineral by DXA are present in prepubertal
      children. The subjects were 336 healthy Asian, black, and white prepubertal
      children (172 females and 164 males). Total body bone mineral content (TBBMC) was
      adjusted for total body BA (TBBA), age, height, and weight. Adjusted mean TBBMC
      was greater in males than in females (p = 0.01). The gender difference was
      independent of ethnicity. Adjusted mean TBBMC was different for black compared
      with nonblack children (p = 0.001). The ethnic difference was a function of TBBA
      and weight. This study in a multiethnic population of prepubertal children shows
      (1) a gender difference in TBBMC and (2) an ethnic difference in TBBMC.

PMID- 10893690
TI  - Biochemical markers as predictors of rates of bone loss after menopause.
AB  - Biochemical markers of bone turnover may correlate with rates of bone loss in a
      group of postmenopausal women, but it is uncertain how useful they are in
      predicting rates of bone loss in the individual. The aim of this study was to
      determine the value of measurements of biochemical markers for the prediction of
      rates of bone loss in the individual. We studied 60 postmenopausal women (ages,
      49-62 years), 43 of whom had gone through a natural menopause 1-20 years
      previously and 17 of whom had undergone hysterectomy 3-22 years ago. Lumbar spine
      bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry
      (DXA) over 2-4 years. Bone formation markers (bone-specific alkaline phosphatase
      [ibAP] and amino terminal of type I collagen [PINP] and osteocalcin [OC]) were
      measured in serum. Bone resorption markers (N-telopeptide of type 1 collagen
      [NTx] and immunoreactive free deoxypyridinoline [iFDpd]) were measured in urine
      and corrected for creatinine (Cr). Rates of bone loss were calculated as percent
      change per year. We found significant negative correlations (Spearman rank)
      between all measured biochemical markers and rate of change in bone density with
      r values ranging from -0.35 to -0.52. When markers and rates of bone loss were
      divided into tertiles, prediction of bone loss in an individual was poor (kappa <
      0.2). There was an exponential relationship between rate of bone loss and years
      since menopause (YSM) in the 43 women having a natural menopause (r2 = 0.44; p =
      0.008) indicating higher rates of loss in the early postmenopausal period. Levels
      of NTx, iFDpd, and PINP also showed a significant negative correlation with YSM.
      We conclude that there is a strong relationship between rates of spinal bone loss
      and levels of bone turnover markers. Although this is a small study, the results
      also suggest that using DXA measurements of the lumbar spine as the "gold
      standard," it is not possible to use biochemical markers to predict rate of bone
      loss in the individual.

PMID- 10893691
TI  - Hormonal and biochemical parameters and osteoporotic fractures in elderly men.
AB  - Low testosterone has been associated with hip fracture in men in some studies.
      However, data on other hormonal parameters and fracture outcome in men is
      minimal. This study examined the association between free testosterone (free T)
      estradiol (E2), sex hormone-binding globulin (SHBG), 25-hydroxyvitamin D
      [25(OH)D], parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), and
      fracture in 437 elderly community-dwelling men. Age, height, weight, quadriceps
      strength, femoral neck bone mineral density (FN BMD), and fracture data (1989
      1997) also were obtained. Fractures were classified as major (hip, pelvis,
      proximal tibia, multiple rib, vertebral, and proximal humerus) or minor
      (remaining distal upper and lower limb fractures). Fifty-four subjects had a
      fracture (24 major and 30 minor). There was no association between minor
      fractures and any hormonal parameter. Risk of major fracture was increased 2-fold
      for each SD increase in age, decrease in weight and height, and increase in SHBG,
      and risk of major fracture was increased 3-fold for each SD decrease in
      quadriceps strength, FN BMD, and 25(OH)D (univariate logistic regression).
      Independent predictors of major fracture were FN BMD, 2.7 (1.5-4.7; odds ratio
      [OR]) and 95% confidence interval [CI]); 25(OH)D, 2.8 (1.5-5.3); and SHBG, 1.7
      (1.2-2.4). An abnormal value for three factors resulted in a 30-fold increase in
      risk but only affected 2% of the population. It is not immediately apparent how
      25(OH)D and SHBG, largely independently of BMD, may contribute to fracture risk.
      They may be markers for biological age or health status not measured by methods
      that are more traditional and as such may be useful in identifying those at high
      risk of fracture.

PMID- 10893692
TI  - Serial changes in bone mineral density and bone turnover after correction of
      secondary hyperparathyroidism in a patient with pseudohypoparathyroidism type Ib.
AB  - Pseudohypoparathyroidism (PHP) is a disorder characterized by hypocalcemia and
      secondary hyperparathyroidism caused by primarily renal resistance to the effects
      of parathyroid hormone (PTH). However, as an indication of normal PTH
      responsiveness in bone, some patients with PHP develop skeletal disease because
      of longstanding secondary hyperparathyroidism. A patient is described with
      hypocalcemia, hyperphosphatemia, marked secondary hyperparathyroidism, and an
      increased alkaline phosphatase level. Subsequent evaluation revealed a diagnosis
      of PHP type Ib. The patient had radiographic evidence of skeletal disease caused
      by secondary hyperparathyroidism. A urinary level of N-telopeptide cross-links of
      type I collagen (NTX) was elevated markedly. Bone mineral density (BMD) was in
      the normal range at all measured sites, with BMD at the spine being higher than
      at the femur and distal radius. Treatment was initiated with calcium and
      calcitriol. Seven months later, calcium and PTH levels had normalized. The level
      of urinary NTX fell by 83%. Spinal BMD improved by 15%, and BMD at the femoral
      neck improved by 11%. Radial BMD was unchanged. This case emphasizes the
      importance of evaluating patients with PHP for hyperparathyroid bone disease and
      shows that correction of secondary hyperparathyroidism in patients with PHP can
      result in a significant suppression of previously accelerated bone turnover and
      to substantial gains in BMD at sites containing a major percentage of cancellous
      bone. The case also implies that assessment of bone turnover with urinary NTX and
      measurement of BMD with dual-energy X-ray absorptiometry (DEXA) may be useful in
      following the response of the skeleton to therapy in these patients and suggests
      the need for more studies of both NTX and BMD in patients with PHP.

PMID- 10893693
TI  - Posterior-anterior and lateral dual-energy x-ray absorptiometry for the
      assessment of vertebral osteoporosis and bone loss among older men.
AB  - Lateral spine dual-energy x-ray absorptiometry (DXA) selectively measures the
      trabecular-rich vertebral bodies without the contributions of the cortical-rich
      posterior elements of the spine and is less affected by spinal degenerative
      disease than posterior-anterior DXA. We tested whether lateral DXA detects
      vertebral osteoporosis more often and is more sensitive to age-related bone loss
      than posterior-anterior DXA in 193 healthy, community-dwelling men aged 51-81
      years (mean +/- SD; 67 +/- 8 years). All men had supine lateral, posterior
      anterior, and proximal femur DXA scans on a Hologic QDR 2000 densitometer. A
      subset (n = 102) had repeat scans after 4 years to determine annualized rates of
      change in bone mineral density (BMD). Age was inversely and significantly
      associated with BMD in the midlateral (r = -0.27) and lateral (r = -0.24) but not
      posterior-anterior (r = 0.04) projections. Midlateral (-1.43 +/- 3.48% per year;
      p = 0.0001), lateral (-0.27 +/- 1.68% per year; p = 0.12), and hip (-0.19 +/-
      1.02% per year; p = 0.06) BMD decreased, whereas posterior-anterior BMD increased
      (0.73 +/- 1.11% per year; p = 0.0001) during follow-up. When compared with normal
      values in 43 men aged 21-42 years, mean T scores were significantly lower with
      lateral (-1.47 +/- 1.32) and midlateral (-1.57 +/- 1.36) than posterior-anterior
      (-0.12 +/- 1.30; p < 0.0001) DXA. Only 2.6% of the older men were considered
      osteoporotic (T score < or = -2.5) at the posterior-anterior spine, whereas 11.0%
      were osteoporotic at the femoral neck, 22.5% at the lateral spine, and 24.6% were
      osteoporotic at the midlateral spine. We conclude that supine lateral DXA
      identifies considerably more men as osteoporotic and is more sensitive to age
      related bone loss than posterior-anterior DXA. Spinal osteoporosis may represent
      a substantially greater health problem among older men than previously
      recognized.

PMID- 10893694
TI  - The effects of selected drugs on the in vitro protein binding of repaglinide in
      human plasma.
AB  - This study investigated plasma protein binding by the novel oral hypoglycemic
      agent, repaglinide, and assessed the influence of other protein-bound drugs upon
      this process. Varying concentrations of [3H]-repaglinide (0.01 to 100
      micrograms/ml) were incubated in solutions of plasma proteins (human serum
      albumin, HSA; alpha 1-acid glycoprotein, AAGP), or human plasma in the absence or
      presence of several test drugs. Protein binding was assessed using an
      ultrafiltration technique. At all concentrations tested, the mean binding of
      repaglinide in plasma was 98.5%, binding to HSA averaged 98.6%, and the binding
      to AAGP was saturable and remained below 50%. Warfarin 10 micrograms/ml,
      furosemide 0.2 microgram/ml, and tolbutamide 100 micrograms/ml, significantly
      reduced in vitro binding of repaglinide at 1 and 100 micrograms/ml versus control
      (p < 0.05), producing an 18-36% increase in free repaglinide. No reduction was
      found using 0.1 microgram/ml repaglinide. Diazepam, glibenclamide and nicardipine
      hydrochloride had no significant effects on the in vitro protein binding of
      repaglinide. These data suggest that the binding of repaglinide to HSA in human
      plasma has potential clinical significance, and that within the therapeutic range
      for repaglinide, the presence of the test drugs has no clinically relevant
      effects on repaglinide binding to plasma proteins.

PMID- 10893695
TI  - Interactions between phenylephrine, clonidine and xylazine in rat and rabbit
      aortas.
AB  - The interaction of the alpha 2-adrenoceptor agonists clonidine and xylazine with
      the alpha 1-adrenoceptors in the rat and rabbit aortas was investigated. In
      preparations preconstricted with phenylephrine (10(-6) M), cumulative addition of
      clonidine and xylazine induced concentration-related vasodilatation in the
      presence of the alpha 2-adrenoceptor antagonist yohimbine and the beta-blocker
      propranolol. Neither clonidine nor xylazine treatment inhibited 5-HT- and KCl
      induced vasoconstriction. It is concluded that alpha 2-agonists have affinity for
      alpha 1-adrenoceptors in rat and rabbit aortas.

PMID- 10893696
TI  - The kinetics of tiazofurin uptake by the isolated perfused choroid plexus of the
      sheep.
AB  - Tiazofurin (TZF-beta-D-ribofuronosyl thiazole-4-carboxamide, NSC-286193) is a
      synthetic nucleoside analog with potent antitumor activity. Isolated choroid
      plexuses (CP) of sheep were perfused in situ and the uptake of [3H]-tiazofurin
      was determined in relation to the recovery of [14C]-mannitol by means of the
      paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 +/
      0.84% and was shown to be both carrier-mediated, sodium-dependent and inhibited
      by adenosine which suggests that it uses the carrier for endogenous nucleosides.
      However, the total tiazofurin uptake into the choroid plexus was negligible (0.93
      +/- 1.97%) as a result of a high backflux, indicating that tiazofurin is not
      trapped within the cells of the CP to any significant degree. The kinetics for
      the uptake into the CP were more favorable than for its passage across the blood
      brain barrier with a Km of 7.71 +/- 1.42 microM, a Vmax of 1.30 +/- 0.05
      microM/min/g and a negligible constant of a free diffusion (Kd) which suggests
      that the CP/CSF route may act as an alternative pathway into the brain.

PMID- 10893697
TI  - Effect of succinylcholine on the neuromuscular junction of hypoglycemic rats.
AB  - The aim of the present study was to investigate the effect of neuromuscular
      blocking drugs on the neuromuscular junction in hypoglycemic rats. Three groups
      of 6 white adult Wistar albino rats were used. Group A consisted of the control
      animals with normal blood glucose levels ranging between 80-120 mg/dl. Groups B
      and C consisted of animals which were made hypoglycemic by intravenous injection
      of insulin at a dose of 1 iU/100 g b.w. In this way, their blood glucose levels
      were reduced to 50% of the blood glucose levels of the control animals. The test
      animals (groups B and C) were sacrificed 40 min after the injection of insulin
      and the preparations of the phrenic nerve-hemidiaphragm were placed into a 100
      ml_bath containing Paradelis-Zaimis solution. The bath was aerized with
      O2/CO2:95/5%, it's temperature was maintained at 37 degrees C and it's pH at 7.2.
      After the stabilization of the system and the recording of neuromuscular
      activity, succinylcholine was administered (1.5 x 10(-8) M in groups A and B and
      3.0 x 10(-8) M in group C). For the statistical analysis of the results,
      student's t-test was used. According to our results, there is a statistically
      significant difference (with p < 0.02 being considered significant) between the
      n.bl/t% (magnitude of final neuromuscular blockage) values of the animals of
      groups B and C and those of the animals of group A. We also observed a
      statistically significant difference (with p < 0.001 being considered
      significant) between the t (time required for complete blockage in groups A and C
      or time required for stabilization of blockage in group B) values of the animals
      of groups B and C and those of the animals of group A. On the other hand, there
      was a statistically significant difference (p < 0.02 being considered
      significant) in the n.bl/5'% (magnitude of neuromuscular blockage 5 min after the
      administration of succinylcholine) values only between the animals of group A and
      B. Our results indicate that under hypoglycemic conditions, the amount of
      succinylcholine required for final neuromuscular blockage is two times greater
      than that needed under normal glucose blood levels. This finding suggests that
      the integrity of the neuromuscular junction is altered during hypoglycemia.

PMID- 10893698
TI  - Role of angiotensin-converting enzyme inhibitor, lisinopril, on spermatozoal
      functions in rats.
AB  - Angiotensin-converting enzyme is present in the male reproductive system but its
      role in the physiology of reproduction is not known. To see the effect of
      angiotensin-converting enzyme on spermatozoal functions, lisinopril, an
      angiotensin-converting enzyme inhibitor, was administered orally using two
      different doses (10 and 20 mg/kg/day) to rats. Both short-term (2 weeks) and long
      term (6 weeks) effects of the drug were observed. Lisinopril treatment resulted
      in a marked decrease in sperm density, sperm motility and zona pellucida
      penetration. Acrosome reaction by spermatozoa obtained from drug-treated animals
      was significantly lower when compared with spermatozoa from normal animals.

PMID- 10893699
TI  - The mechanism responsible for the drowsiness caused by first generation H1
      antagonists on the EEG pattern.
AB  - The present study was performed to clarify the mechanism responsible for the
      drowsiness caused by first generation H1 antagonists according to
      electroencephalogram activity. All H1 antagonists used in the present study
      caused the EEG-recorded drowsiness pattern, i.e., increases in EEG power spectra
      of the delta and theta bands at the frontal cortex in rats. The potency of
      cyproheptadine was greater than those of diphenhydramine and promethazine, while
      that of pyrilamine was less than those of the other drugs examined. The increase
      in EEG power spectra in the delta band induced by H1 antagonists was antagonized
      by pretreatment with both histidine and physostigmine. The effect of pyrilamine
      was more potently antagonized by histidine and less potently antagonized by
      physostigmine as compared to diphenhydramine, promethazine and cyproheptadine.
      The increases in EEG power spectra induced by H1 antagonists were neither
      antagonized nor potentiated by 5-hydroxytryptophan. These results clearly
      indicate that the increases in EEG power spectra in the delta and theta bands at
      the frontal cortex in rats induced by first generation H1 antagonists are
      responsible for both histaminergic and cholinergic mechanisms.

PMID- 10893700
TI  - Effect of muscarinic receptor agonists on animal models of psychosis.
AB  - The purpose of this study was to determine the effects of muscarinic receptor
      agonists on models of psychosis in rats. A battery of three tests, catalepsy
      (haloperidol-induced) augmentation, amphetamine-induced stereotypy antagonism and
      conditioned avoidance response were used. Both muscarinic receptor agonists
      physostigmine and pilocarpine produced similar results. They dose-dependently
      augmented the haloperidol-induced catalepsy, inhibited amphetamine-induced
      stereotypy behavior and inhibited the conditioned avoidance response. Results
      demonstrate that muscarinic receptor agonists have actions similar to those of
      dopamine receptor antipsychotic drugs in animal models, suggesting that
      muscarinic receptor agonists may be used as adjuvant drugs in the treatment of
      psychosis.

PMID- 10893701
TI  - Acute and subacute toxicities of theophylline are directly reflected by its
      plasma concentration in dogs.
AB  - The purpose of this study was to evaluate the relationship between acute and
      subacute toxicity and blood levels of theophylline in dogs. Theophylline was
      administered intravenously into dogs once (at doses of 50, 100 and 150 mg/kg) or
      for 4 weeks (at doses of 20, 35 and 70 mg/kg/day). In the single dose toxicity
      study, by increasing the dose of theophylline, plasma concentration increased and
      the severity of toxic symptoms were intensified. After a single dosing of
      theophylline, accentuated heart rate and vomiting were observed at a
      concentration of more than 67 micrograms/ml, and excitement, spasm and hyperpnea
      were observed at more than 130 micrograms/ml. Animals died after tonic convulsion
      at 180 micrograms/ml. In the repeated dose toxicity study, the plasma
      concentration of theophylline increased dependent on dosage, and was not affected
      by repeated dosing. Even under these conditions, the toxic symptoms were quite
      similar to those of the single dose, except for an additional decrease in
      movement, body weight reduction and myocardial lesion. These present results
      suggest that the severity of theophylline toxicity is dependent on its plasma
      concentrations rather than accumulated dosages. The blood concentration of
      theophylline-treated patients should be maintained within the therapeutic range
      in order to diminish risk.

PMID- 10893702
TI  - Pharmacokinetic study of theophylline in dogs after intravenous administration
      with and without ethylenediamine.
AB  - Aminophylline (ethylenediamine salt of theophylline) and Theodrip, a new
      formulation of theophylline developed by Nikken Chemicals, are drugs for the
      treatment of acute bronchial asthma in injectable form. The present study was
      conducted using dogs to first confirm the bioequivalence of the two injectable
      forms containing theophylline and aminophylline and to secondly clarify the
      influence of the rate of venous infusion on the pharmacokinetics of theophylline
      in plasma. The following results were obtained: 1) Pharmacokinetic parameters of
      plasma theophylline after an intravenous bolus injection were close to those
      after the dosing of aminophylline in dogs by a crossover method. Thus, the 95%
      confidence limits of mean value differences of Cmax, t1/2 and AUC between the two
      injection forms were in the range of -3.16-4.28%, -6.19-7.28% and -7.23-5.28%,
      respectively. These results indicate the bioequivalence between theophylline and
      aminophylline in dogs from a pharmacokinetic point of view as well as the lack of
      influence of ethylenediamine on the pharmacokinetics of theophylline. 2) After
      the intravenous bolus injection (30 sec) and the 15-min constant rate infusion of
      theophylline to dogs, the plasma concentrations of theophylline were 27.37 +/-
      3.67 micrograms/ml and 18.34 +/- 2.32 micrograms/ml immediately after the
      completion of administration, respectively. It is notable that in humans the
      former concentration level has been observed to frequently cause adverse effects,
      whereas the latter was in the safe range. Consequently, the 15-min constant rate
      infusion did not result in the rapid increase in the plasma theophylline
      concentrations and was superior to the bolus injection from the viewpoint of
      maintaining the safety plasma concentrations. In conclusion, to avoid
      hypersensitivity due to ethylenediamine and the adverse effects caused by high
      plasma concentrations of theophylline, it was considered that constant rate
      infusion of theophylline to the venous is preferable in the clinical setting.

PMID- 10893703
TI  - Effects of the NMDA receptor antagonist ketamine in electrically induced A delta
      fiber pain.
AB  - OBJECTIVES: Both ketamine and pethidine have previously been found to have
      analgesic effects in experimentally induced C-fiber pain. The aim of the present
      study was to examine the effects of ketamine and pethidine in A delta-fiber
      mediated pain induced by electrical tooth stimulation. METHODS: In this double
      blind crossover study, an upper right central incisor was stimulated by a Bofors
      electrical stimulator before and after the intravenous administration of drugs.
      According to a randomized protocol and with a one-week wash-out period, 9 healthy
      female volunteers were given either racemic ketamine 0.3 mg/kg or pethidine 0.7
      mg/kg, and 11 participants were given (R)-ketamine 0.5 mg/kg or (S)-ketamine 0.15
      mg/kg. Pain thresholds were registered by an amperemeter on the stimulator. Drug
      induced side effects were registered by use of a standardized questionnaire and
      visual analog scales. RESULTS: Both ketamine and pethidine gave significant but
      short-lasting increases in pain thresholds compared to no medication. The
      participants reported more pronounced mental side effects after ketamine
      injection. A comparison of (R)- and (S)-ketamine revealed no statistical
      difference in the effect on pain thresholds of the two enantiomers at the present
      doses, but 7 out of 11 participants reported to have fewer and less pronounced
      side effects from (R)-ketamine than from (S)-ketamine. CONCLUSIONS: Ketamine and
      pethidine have only a marginal effect on pain thresholds in electrically induced
      A delta-fiber-mediated tooth pulp pain, in contrast to the analgesic effects
      previously found in experimental and postoperative C-fiber-mediated pain. The
      ketamine enantiomers at the doses used in this study showed equal analgesic
      properties but different side effect profiles.

PMID- 10893704
TI  - Screening methods for antiasthmatic agents.
AB  - Bronchial asthma is characterized by both bronchoconstriction and airway
      inflammation which leads to bronchial hyperresponsiveness to various stimuli.
      Different mediators are implicated in asthma. As the precise etiology is not
      known and multiple biochemical processes are triggered by different causative
      factors, it is difficult to have a single drug which can effectively and
      simultaneously act upon different mediators. This led to an intense search for
      potent and safe antiasthmatic drugs. This review intends to compile different
      screening methods for the evaluation of new candidate drugs with potential for
      the treatment of asthma. These include in vitro, in vivo, receptor binding and
      enzymatic methods. Detailed experimental methods have been included with
      appropriate literature citations.

PMID- 10893705
TI  - Synthesis and antiviral activity of 3-(beta-D-ribofuranosyl)-1,2,4-oxadiazole-5
      carboxamide.
AB  - 3-(beta-D-Ribofuranosyl)-1,2,4-oxadiazole-5-carboxamide (5) was prepared by
      condensation reaction of amidoxime 6 with monoethyl oxaloyl chloride followed by
      reaction with ammonia. The compound 5, however, did not exhibit any significant
      activity against herpes simplex virus type-I (HSV-I) and semliki forest virus
      (SFV).

PMID- 10893706
TI  - Synthesis of N,N-dialkylaniline-2'-deoxyuridine conjugates for DNA-mediated
      electron transfer studies.
AB  - Syntheses of two analogs of deoxyuridine with N,N-dialkylaniline chromophores are
      reported. 5-[3-(N-methylphenylamino)propanoyl]-2'-deoxyuridine (1) and 5-[2-(4
      N,N-dimethylaminophenyl)ethyl)]-2'-deoxyuridine (2) are prepared by palladium
      mediated coupling. Preparation of 2 was facilitated by in situ transient O4
      trimethylsilyl protection during alkynylation which suppressed secondary
      cyclization of the coupling adduct.

PMID- 10893707
TI  - Synthesis of unsaturated carboacyclic nucleoside analogues via Mitsunobu
      reactions.
AB  - 2-Substituted allyl alcohols 9 and 14 were prepared starting from butane-1,2,4
      triol and glycerol, respectively. Mitsunobu condensations of 9 and 14 with purine
      and pyrimidine bases, followed by deprotection, afforded a number of
      acyclonucleosides having 4-hydroxy-2-methylenebutyl or 3,3-bis(hydroxymethyl)-2
      methylenepropyl chain.

PMID- 10893708
TI  - Synthesis of [bis(inosine-5')]-tetraphosphate and [bis(inosine-5')]
      pentaphosphate analogues bearing the residues of methylenediphosphonic acid.
AB  - Various methods of synthesis of metabolically stable phosphonate analogues of
      bisnucleoside oligophosphates containing two residues of methylenediphosphonic
      acid in the oligophosphate chain are studied. Phosphonate analogues of Ip4I and
      Ip5I are prepared.

PMID- 10893709
TI  - Kinetic studies on Ce(IV)-induced hydrolysis of single-stranded and double
      stranded oligonucleotides.
AB  - The Ce(IV)-induced hydrolyses of DNA are kinetically investigated. The formation
      constants of the Ce(IV)-DNA complexes are in the following order: the single
      stranded DNA > the double-stranded DNA >> the dinucleotide. On the other hand,
      the catalytic rate constants for the single-stranded DNA and the double-stranded
      DNA are comparable with each other, but both of them are much smaller than the
      value for the dinucleotide hydrolysis.

PMID- 10893710
TI  - Synthesis and NMR characterization of diastereomeric CPSMeG derivatives.
AB  - Synthesis and stereochemical characterization of enantiomerically pure CPSMeG
      derivatives by NMR methods are reported. The effect of 5'-dimethoxytrityl on the
      conformational properties is described. It was found that in P-diastereomers the
      conformational differences about the C3'-O3' bond, as discernible from the delta
      J values, are enhanced by the presence of this protecting group.

PMID- 10893711
TI  - The chemical synthesis of oligoribonucleotides with selectively placed 2'-O
      phosphates.
AB  - A phosphoramidite, solid support method for the chemical synthesis of
      oligoribonucleotides containing 2'-O-phosphate at a selected position is
      presented. Synthesis of these oligoribonucleotides is based on uridine- and
      adenosine-(2'-O-phosphate)-3'-phosphoramidites, and a new condition for removal
      of 2'-O-phosphate protecting groups, which does not cleave internucleotide bonds.
      The structure of oligoribonucleotides with 2'-O-phosphate has been proven by
      enzymatic digestions and dephosphorylation by yeast 2'-phosphotransferase.

PMID- 10893712
TI  - A convenient synthesis of a novel nucleoside analogue: 4-(alpha-diformyl-methyl)
      1-(beta-D-ribofuranosyl)-2-pyrimidinone.
AB  - The nucleoside analogue 4-(alpha-diformyl-methyl)-1-(beta-D-ribofuranosyl)-2
      pyrimidinone (5) was prepared from the corresponding 4-methyl pyrimidinone
      nucleoside by means of the Vilsmeier reaction. The unprotected nucleoside can be
      phosphorylated directly with phosphorus oxychloride in triethyl phosphate.

PMID- 10893713
TI  - Studies on epimeric D-xylo-and D-lyxo-tetritol-1-yl-2-phenyl-2H-1,2,3-triazoles.
      Synthesis and anomeric configuration of 4-(alpha-and beta-D-threofuranosyl)-2
      phenyl-2H-1,2,3-triazole C-nucleoside analogs.
AB  - Treatment of 4-(D-xylo-tetritol-1-yl)-2-phenyl-2H-1,2,3-triazole (1) with one
      mole equivalent of tosyl chloride in pyridine solution, afforded the C-nucleoside
      analog; 4-(beta-D-threofuranosyl)-2-phenyl-2H-1,2,3-triazole (2) in 55% yield, as
      well as the byproduct 4-(4-chloro-4-deoxy-D-xylo-tetritol-1-yl)-2-phenyl-2H-1,2,3
      triazo le (4). Treatment of the epimeric 4-(D-lyxo-tetritol-1-yl)-2-phenyl-2H
      1,2,3-triazole (6) with tosyl chloride in pyridine solution afforded the anomeric
      C-nucleoside analog; 4-(alpha-D-threofuranosyl)-2-phenyl-2H-1,2,3-triazole (7) in
      29% yield, as well as the byproduct 4-(4-chloro-4-deoxy-D-lyxo-tetritol-1-yl)-2
      phenyl-2H-1,2,3- triazole (9). Similar treatment of 1 and 6 with
      trifluoromethanesulfonyl chloride in pyridine solution afforded 2 and 7,
      respectively. The structure and anomeric configuration of these compounds were
      determined by acetylation, NMR, NOE, and circular dichroism spectroscopy, as well
      as mass spectrometry.

PMID- 10893714
TI  - Investigation of a facile synthetic method for phosphorothioate dimer synthons in
      oligonucleotide phosphorothioates synthesis.
AB  - A facile synthetic method of a phosphorothioate dimer block was investigated.
      Dinucleoside phosphite triester intermediates were obtained in one-pot synthesis
      by the coupling of a protected nucleoside bearing free 5'-OH and a protected
      nucleoside bearing free 3'-OH in the presence of phosphorous trichloride (PCl3)
      and 1,2,4-triazole. The intermediates were easily sulfurized to afford the
      desired phosphorothioate dimer blocks in 33-64% overall yields.

PMID- 10893715
TI  - Inhibition of cell growth and proliferation in human glioma cells and normal
      human astrocytes induced by 8-Cl-cAMP and tiazofurin.
AB  - 8-Cl-cAMP and tiazofurin (TR) are anti-tumor agents that besides their
      antiproliferative effect, also induce differentiation of tumor cells. Although,
      these agents exert a profound effect on the same events of tumor cell life, it is
      thought that 8-Cl-cAMP and TR act by modulating the signal transduction pathway
      through distinct mechanisms. We have compared their effect on two human glioma
      cell lines (U87 MG and U251 MG) and examined if there is selectivity in their
      action toward normal human astrocytes.

PMID- 10893716
TI  - The nonenzymatic hydrolysis of oligoribonucleotides. VII. Structural elements
      affecting hydrolysis.
AB  - Several elements of oligoribonucleotide structure are important for efficient
      hydrolysis. We have found that the following factors influence
      oligoribonucleotide hydrolysis: (i) single-stranded structure of RNA flanking the
      scissile phosphodiester bond, (ii) the substituent on atom C-5 of the uridine
      adjacent to the cleaved internucleotide bond, (iii) the position of the scissile
      UA phosphodiester bond within a hairpin loop, (iv) the concentration of
      formamide, urea, ethanol and sodium chloride.

PMID- 10893717
TI  - Prooligonucleotides exhibit less serum-protein binding than phosphodiester and
      phosphorothioate oligonucleotides.
AB  - The protein-binding properties of dodecathymidine derivatives (prooligos) bearing
      either methyl- or tert-butyl-S-acylthioethyl (Me- or tBuSATE) protecting groups
      were evaluated. The dissociation constants (Kd) were estimated for complexes of
      prooligos with serum blood proteins and lactoferrin using prooligos to compete
      the binding of the radiolabeled, alkylating probe oligonucleotide CIRp(T)12 with
      the proteins. tBuSATE and MeSATE prooligos have decreased affinity of binding
      with serum proteins and lactoferrin compared with their parent oligos. These data
      suggest that prooligos should cause less side effects which combined with their
      stability to nucleases and enhanced permeability into cells make them potentially
      useful for design of therapeutics.

PMID- 10893718
TI  - Synthesis of 6-alkyl- and arylamino-9-(tetrahydro-2-pyranyl)purines via 6
      methylsulfonylpurine.
AB  - A series of six potential plant hormones, 6-alky- and arylamino-9-(tetrahydro-2
      pyranyl)purines were prepared in three steps in 35 to 45% overall yield from 6
      methylthiopurine via 6-methylsulfonylpurine.

PMID- 10893719
TI  - Synthesis and antiviral activity of C-5 substituted analogues of d4T bearing
      methylamino- or methyldiamino-linker arms.
AB  - A general strategy is reported for the preparation of C-5-methylamino- or
      methyldiamino-d4T analogues of "different sizes". Reactions of the 2',3'
      didehydro-2',3'-dideoxy-C-5 hydroxymethyl precursor (7) with either polymethylene
      diamines (n = 6, 8, 10 and 12) or propargylamine proceed regioselectively via
      substitution reactions at the C-5 position of uracil. The compounds were
      evaluated for antiviral activity and cytotoxicity. No significant activity was
      observed for compounds 9, 11, and 13, but 10 and 12 exhibited a weak activity
      against HIV-1.

PMID- 10893720
TI  - Synthesis, mechanism and fluorescence properties of 8-(aryl)-3-beta-D
      ribofuranosylimidazo[2,1-i]purine 5'-phosphate derivatives.
AB  - The synthesis of new fluorescent nucleotides is described. This synthesis
      comprises two parallel reactions, the Kornblum oxidation and imidazole formation,
      which lead to 8-(aryl)-3-beta-D-ribofuranosylimidazo[2,1-i]purine 5'-phosphates 2
      from AMP or ATP. A detailed mechanism is proposed based on monitoring the
      reaction by 1H- and 13C-NMR spectroscopy, MS, FAB, HPLC, and pH meter. The
      spectral and fluorescent properties of the new derivatives at various pH values
      are described. Excitation and emission maxima for 3 were observed at 290 and 420
      nm, respectively, in both basic and neutral media. In acidic media, the emission
      maximum shifted to 410 nm, however, the fluorescence intensity increased 1.5
      fold. ATP analogues 2b and 3b exhibited relative stability regarding hydrolysis
      by type II ATPDase. Compound 3b is relatively chemically stable at pH 10.4 and
      7.4.

PMID- 10893721
TI  - Care of the medical ethos, with some comments on research: reflections after the
      holocaust.

PMID- 10893722
TI  - The legacy of academic medicine and human exploitation in the Third Reich.

PMID- 10893723
TI  - Nazi science and Nazi medical ethics: some myths and misconceptions.

PMID- 10893724
TI  - Nuremberg's legacy: some ethical reflections.

PMID- 10893725
TI  - Law and public policy in human studies research.

PMID- 10893726
TI  - Medicine and conscience: the debate on medical ethics and research in Germany 50
      years after Nuremberg.

PMID- 10893727
TI  - The Pernkopf story: the Austrian perspective of 1998, 60 years after it all
      began.

PMID- 10893728
TI  - The Medical Faculty of the University of Vienna 60 years following Austria's
      annexation.

PMID- 10893729
TI  - Diuresis and diarrhea: is the gut a misunderstood nephron?

PMID- 10893730
TI  - Infectious causation of disease: an evolutionary perspective.

PMID- 10893731
TI  - [Lewy body dementia: some contributions to the clinical knowledge].
AB  - INTRODUCTION: Dementia with Lewy bodies is the second commonest type of dementia.
      The latest criteria for its diagnosis have recently been established (1996).
      PATIENTS AND METHODS: We report the clinical findings in 25 patients with
      probable dementia with Lewy bodies. RESULTS: No sex predominance was seen, onset
      was after the age of 65 years in 60% of the cases and there was a past history of
      dementia in 48%. Onset was with cognitive disturbances in 32%, Parkinsonism in
      32% and both in 32%. When there was an interval between Parkinsonism and
      dementia, this was of 3-19 months. The dementia included attention disorder,
      impaired recall and praxis alterations. Disorders of executive function,
      behaviour or language, were seen in two thirds of the patients and acalculia in
      over half. Around 50% showed signs of subcortical involvement different from
      Parkinsonism. Parkinsonism was basically hypokinetic (96%), with tremor in two
      thirds of the cases, at rest (29%) postural (12%) or combined (59%), and
      symmetrical in 41%. Rigidity was only seen in 52% and was slight in most cases.
      In 16% there was weakness of vertical gaze. In 40% urine or double incontinence
      occurred, mainly when the dementia was at an intermediate or advanced state.
      CONCLUSIONS: Dementia with Lewy bodies is a dementia with fronto-temporo-parietal
      alterations, frequently associated with hypokinetic Parkinsonism (which always
      shows a lag period with respect to dementia of less than 24 months),
      hallucinations and a fluctuating course. Other findings supporting this diagnosis
      were seen in two out of every three patients.

PMID- 10893732
TI  - [Life events, quality of life and social support prior to acute cerebral vascular
      disease, as predictive factors of the quality of life and functional state
      following stroke].
AB  - INTRODUCTION: The repercussion of stroke on quality of life has been evaluated
      but not the possible relation between the quality of life before and months after
      an acute stroke. OBJECTIVE: To study the possible relation between quality of
      life, social support, stressful life events prior to the stroke and quality of
      life, social support and functional state months after. PATIENTS AND METHODS: A
      prospective study was made of 34 patients (71.7 +/- 8 years; 19 (56%) men; 15
      (44%) women with stroke, by means of two evaluations: personal interview within
      the first 36 hours (quality of life--Nothingham health profile (NHP)-, perception
      of social support and stressful life events--Holmes and Rake inventory-) and an
      interview over the phone 16.5 +/- 5.3 months after the stroke (NHP, perception of
      social support and functional state--Rankin scale-). RESULTS: Following the
      stroke there was deterioration in perception of social support (19.8 +/- 3 vs
      12.5 +/- 8; p = 0.000) and in the degree of social isolation of the NHP (9.4 +/-
      20 vs 21.1 +/- 30; p = 0.03). The only relation found was between the following
      variables: pain at the first evaluation and pain (r = 0.45; p = 0.007) at the
      second evaluation; mobility at the first evaluation and emotional state (r =
      0.39; p = 0.029) and social support (r = 0.37; p = 0.027) at the second
      evaluation; sleepiness at the first evaluation and energy (r = 0.55; p = 0.0006),
      pain (r = 0.39; p = 0.022), emotional state (r = 0.35; p = 0.038), mobility (r =
      0.34, p = 0.048) and sleepiness (r = 0.51; p = 0.001) at the second evaluation.
      CONCLUSION: Our results indicate that there is little relationship between the
      previous state and that following stroke, and that the deterioration in
      perception of support and social isolation is due to the stroke itself.

PMID- 10893733
TI  - [False negatives in the diagnosis of myasthenia gravis].
AB  - INTRODUCTION: Myasthenia gravis is an uncommon disorder with very variable
      clinical findings. This often leads to errors in diagnosis. OBJECTIVE: To study
      the main errors leading to false negatives in the diagnosis of myasthenia gravis.
      PATIENTS AND METHODS: We carried out a questionnaire to determine all the doctors
      and diagnoses made by them in relation to symptoms of myasthenia graves in 109
      patients in whom this diagnosis was later confirmed when a specialist was
      consulted. RESULTS: Most of the patients went to a general practitioner first.
      During this initial consultation the disease was only diagnosed in 10 cases
      (9.2%) and neurosis was the most frequent diagnosis (27.5%). Although most
      patients had to see from two to four doctors before diagnosis was made, there was
      no major delay in this. In 84 of the 109 cases the diagnosis was established
      within the first six months, generally by a neurologist (86.2%) and less
      frequently by a general physician (11.0%). CONCLUSION: General practitioners,
      ophthalmologists, psychiatrists and otorhinolaryngologists are often involved in
      the evaluation of these cases although they made little contribution to the
      diagnosis.

PMID- 10893734
TI  - [Patterns of immunoglobulin synthesis in pediatric patients with Coxsackie A9
      meningoencephalitis during the neuropathy epidemic in Cuba].
AB  - INTRODUCTION: Simultaneously with the origin and development of the Cuban
      epidemic neuropathy, cases of viral meningoencephalitis with particular
      characteristics due to Coxsackie were found. This virus and Inoue-Melnick virus
      were found too in patients suffering from Cuban epidemic neuropathy. PATIENTS AND
      METHODS: 31 pediatric patients suffering from viral meningoencephalitis were
      studied. Albumin, IgA, IgM and IgG were quantified in serum and cerebrospinal
      fluid by nephelometry. Cytochemical studies and reibergrams were performed.
      RESULTS: There was a lymphocyte predominance in cerebrospinal fluid. A
      dysfunction of blood-cerebrospinal fluid barrier was shown in 10 patients. Twenty
      patients have no immunoglobulins intrathecal synthesis. The synthesis patterns
      were: five patients with local IgM synthesis, two patients with local IgG
      synthesis and IgA + IgM. IgA + IgG and IgA + IgM pattern was synthesized in one
      patient respectively. Two patients with low IgG synthesis percentage or IgG
      intrathecal fractions were reported. CONCLUSIONS: The absence of immunoglobulins
      intrathecal synthesis and the immunoglobulins synthesis patterns differ from
      other pediatric patients with enterovirus meningoencephalitis. These patterns may
      have relationship with modified antigenic characteristics of the virus, also
      found in Cuban epidemic neuropathy.

PMID- 10893736
TI  - [Diagnostic error of mental retardation of neurometabolic origin confirmed by
      mass sequential spectrometry].
AB  - INTRODUCTION: The metabolic screening test gives the first laboratory indication
      for neurometabolic alterations which can cause mental retardation. Some
      techniques such as thin layer chromatography, are still used in several countries
      to confirm the diagnosis of inborn errors of metabolism after a general screening
      test. PATIENTS AND METHODS: Two patients from a mentally retarded Colombian
      population were reported positive for the Nitrosonaphtol test, and remained
      positive to tyrosine metabolism alteration by thin layer chromatography,
      suggesting the correspondent management. In the present study we tried to confirm
      the last diagnosis, performing tandem mass spectrometry analysis of
      acylcarnitines and amino acids, on blood samples of all patients from the last
      study, which were found negative for any alteration. CONCLUSION: Is necessary to
      improve the diagnosis methods used in some countries in order to avoid mistakes
      that can change the life-style of the wrongly diagnosed patients.

PMID- 10893735
TI  - [A study of the tolerability and effectiveness of nicardipine retard in cognitive
      deterioration of vascular origin].
AB  - INTRODUCTION: Nicardipine is a calcium antagonist which in previous trials has
      been shown to be effective in the prevention of stroke and the treatment of its
      sequelae, such as cognitive deterioration of vascular origin. We consider a phase
      IV study at primary care level to analyze the tolerability and efficacy of a
      retarded action formulation of 40 mg nicardipine. PATIENTS AND METHODS: In this
      open, prospective, multicentric trial 6,375 patients took part, of whom 5,593
      were evaluated (87.7%). All were diagnosed as having vascular-type dementia
      (Hachinski > 6) and were given treatment with nicardipine retard (40 mg/day/6
      months). The patients were assessed on the Montorio (daily activity) and SPMSQ
      (cognitive function) scales at the first visit and after one, three and six
      months, together with a record of side effects. RESULTS: Only 0.9% of the
      patients recruited abandoned the study for problems of tolerability of the drug.
      The average improvement seen on Montorio's test was statistically significant
      from the first month, and reached 9% after six months. The 65.5% of the patients
      who started the study in seriously deteriorated condition showed improvement
      after six months. For the SPMSQ test, the average improvement was also
      statistically significant from the first visit and over 40% after six months.
      There was improvement in 64.4% of the patients who were severely deteriorated at
      the start of the study. CONCLUSION: Nicardipine retard is a drug which is safe
      and effective when used for the treatment of mental deterioration of vascular
      origin.

PMID- 10893737
TI  - [Gerstmann's syndrome in a 9 year old boy].
AB  - INTRODUCTION: Gerstmann's syndrome encompasses the tetrad of finger agnosia,
      agraphia, acalculia and right-left confusion and is associated with lesions of
      the left angular gyrus, situated at the confluence of the temporal, parietal and
      occipital lobes. The localizing value of this syndrome has been questioned
      because multiple mechanisms can account for each of the four components of the
      syndrome. This clinical association is infrequent in children and it is
      impossible to diagnose in early stages of life because of parietal lobes have a
      slow functional development during childhood. CLINICAL CASE: We present the case
      of a learning disabled boy, 9 year old and right handed, who developed
      Gerstmann's syndrome. Acalculia, right-left disorientation, agraphia and finger
      agnosia were clearly identified by neuropsychological studies at this time, but
      there was no evidence of this dysfunction when he was first studied being 5 year
      old. This patient had perinatal asphyxia and suffered from focal clonic seizures
      in early neonatal period. In this case, a infarcted lesion was found at the
      confluence of parietal and occipital lobes in cranial CT an MRI scans.
      CONCLUSION: We conclude that is very important to identify this syndrome during
      childhood using a wide range of neuropsychological tests in order to diminish
      learning disorders with an early psychopedagogic supervision.

PMID- 10893738
TI  - [Fibromuscular dysplasia with moyamoya phenomenon in a patient with Alport's
      syndrome. A type IV collagen disorder].
AB  - INTRODUCTION: Alport's syndrome is a hereditary progressive nephropathy
      associated with neurosensorial deafness, secondary to mutations of the genes
      which codify the a chains of collagen IV. In the literature we have found
      isolated reports of cases with nervous system involvement. CLINICAL CASE: A 37
      year old woman was diagnosed as having Alport's syndrome with terminal secondary
      chronic renal failure and bilateral neurosensorial deafness. She was assessed
      following repeated transient ischemic attacks of the left hemisphere over the
      previous three years. Neurological examination was normal. Magnetic resonance
      showed an ischemic stroke of the left frontal white matter, and on arteriography
      there was tubular stenosis of the left extracranial internal carotid artery and
      proximal occlusion of the homolateral anterior and medial cerebral arteries with
      a compensatory deep vascular network, compatible with fibromuscular dysplasia and
      secondary moyamoya phenomenon. CONCLUSIONS: Although the association between
      fibromuscular dysplasia and Alport's syndrome may be casual, we suggest that
      there may be a common mechanism of pathogenesis in both syndromes, related to the
      expression of type IV collagen in the vascular basal membranes.

PMID- 10893739
TI  - [Biophysical foundations of the neuronal activity].
AB  - OBJECTIVE: It is sought to expose in a simple but rigorous way the fundamental
      basis of the classical biophysics. DEVELOPMENT: I start from the basic properties
      of a simple system (two solutions separated by a semipermeable membrane) in order
      to analyze the process of development of differences of potential. It is analyzed
      with special interest the development of the Nernst and Nernst-Planck equations.
      Then it is studied how this difference potential can originate, with different
      ionic species, the resting potential (Goldman, Hodgkin and Katz model). The next
      step consists in to analyze how the action potential arises. To do this, it will
      be of capital importance the mathematical model developed by Hodgkin and Huxley
      in the fifties; for it will be analyzed it thoroughly. Finally, some properties
      of the ionic channels will be commented that symbolize the biological
      implementation of the previous model. CONCLUSION: The fundamental property of the
      nervous system that constitutes its biological sense is the handling of the
      information in a quick and sure way. This information codes it basically in form
      of potentials and its changes. For it, it would be important for clinical
      neurophysiologists, neurologists, neurosurgeons and psychiatrists to understand
      the mechanisms that underlie into the behavior of the nervous system.

PMID- 10893740
TI  - [Genetic association between the reduced amplitude of the P300 and the allele A1
      of the gene which codifies the D2 dopamine receptor (DRD2) as possible biological
      markers for alcoholism].
AB  - INTRODUCTION: Over the last twenty years much work has been done to study the
      P300 in alcoholism. A systematically reduced amplitude, both in patients and in
      populations at risk (children of alcoholics) was found. Besides, studies on twins
      indicate that the waves of the evoked potentials are under genetic control.
      Furthermore, advances in molecular genetic techniques have clarified the part
      played by the allele A1 of the gene which codifies the D2 dopamine receptor in
      alcoholism. Only in recent years have studies been published relating them and in
      these they are considered to be risk markers for alcoholism. However,
      contradictory results have been obtained. DEVELOPMENT: The objective of this
      study is to review part of the literature and find evidence for and against the
      characteristics observed in the P300 and the possible part played by the DRD2
      gene in the aetiology of alcoholism and the relationship between them. At the
      same time we consider the most relevant theoretical aspects of the role played by
      dopamine in the central nervous system, since some studies have shown that it is
      involved in the generation of P300 and reinforcement due to alcohol consumptions.
      Finally, we discuss the advantages and disadvantages that should be taken into
      account when considering the low amplitude of P300 and the presence of the A1
      allele as diagnostic markers to identify populations at risk and thus avoid
      appearance of the disorder.

PMID- 10893741
TI  - [Executive function and its disorders].
AB  - INTRODUCTION: Executive function is a set of cognitive operations, which are
      sustained by the complex activities of the frontal lobe systems. Executive
      function is responsible for programming, establishing goals, classifying,
      executing, controlling, changing, monitoring and confronting all the mental
      activities. OBJECTIVE: To review and to actualize neuropsychological literature
      about executive function, its development, its structure, its theoretical model,
      its alterations in different neurological and neuropsychological disorders, and
      its clinical qualitative and quantitative assessments. CONCLUSION: Executive
      function is a multidimensional construct of the cognition, which is structured
      and modified through the development during childhood, and which is altered
      during different neurological and neuropsychological disorders, and which could
      be evaluated in a qualitative or quantitative approaches.

PMID- 10893742
TI  - [Cognitive function in the obsessive-compulsive disorder associated with cerebral
      lesions].
AB  - INTRODUCTION: Although obsessive-compulsive symptoms are uncommon among patients
      with neurological diseases, structural neuroimaging (CAT or MRI) disclose focal
      brain lesions in some patients. However, little is know about the clinical
      phenomenology of obsessive-compulsive symptoms and the cognitive deficits that
      occur in neurological conditions. OBJECTIVE: To review the cognitive functioning
      of patients who develop an obsessive-compulsive disorder (OCD) in association
      with focal brain lesions. DEVELOPMENT: In the present study, the author review
      recent studies which suggest that OCD associated with brain lesions is relatively
      similar to idiopathic or 'functional' OCD (i.e., OCD unassociated with gross
      brain damage). Idiopathic and acquired forms of OCD are clinically heterogeneous.
      The content of obsessions and compulsions in acquired OCD depends, at least in
      part, of the causative lesion, whereas the pattern of cognitive deficits is more
      homogeneous affecting attention, general intelligence, verbal and visuospatial
      memory, and executive function. CONCLUSION: It is suggested that the study of
      different subgroups of patients with acquired OCD would detect differences in the
      phenomenology of obsessions and compulsions as well as in the pattern of
      cognitive deficits. Moreover, this approach can improve our understanding about
      the pathophysiological mechanisms underlying idiopathic OCD.

PMID- 10893743
TI  - [Organic personality disorder. Conceptual and diagnostic aspects].
AB  - INTRODUCTION: Probably the commonest neuropsychiatric sequela in persons who have
      had some type of cerebral lesion (of whatever origin) are the complaints of
      changes in the personality of the patient prior to the lesion which cause
      problems with the family, socially and at work. These problems have been grouped
      together under the same diagnosis in current psychiatric nosology called 'organic
      personality disorder'. DEVELOPMENT: In this article we wish to point out the
      disadvantages due to this diagnosis which have a double origin. Firstly, it is
      based on the concept of personality, which has been shown to be inconsistent
      throughout the history of science. Secondly, because this group contains
      heterogeneous phenomena and conducts which are probably based on different
      neurobiological processes. CONCLUSION: The development of strategies of
      investigation, and of effective therapeutic techniques for these patients make it
      necessary to separate the different phenomena which, in the author's opinion, are
      erroneously included in this nosological group.

PMID- 10893744
TI  - [Towards a comprehensive theory of the rehabilitation of cerebral function as a
      basis for programmes of rehabilitation in brain damaged patients].
AB  - INTRODUCTION: Definition of the programme on integral rehabilitation needed by
      each patient after a cerebral lesion is today a clinical challenge which still
      requires much investigation. The many advances in all fields of the neurosciences
      give a great stimulus and fresh hope in tackling these problems. For practical
      advances in treatment it is important that clinicians make an effort to explain
      which are the theoretical models used in this complex field of the CNS, or which
      models may be used to develop new programmes of treatment. DEVELOPMENT: In this
      paper we summarize some of the current models of rehabilitation of psychic and
      neuropsychological functions based on experience acquired in the rehabilitation
      of chronic psychiatric patients and the newer findings of neurophysiology, neuro
      imaging, neuropharmacology, neuropsychology etc. We also offer suggestions for
      effective organization of the work of rehabilitation teams. The newer models to
      be developed in the future should be suitable for the determination of what
      should be rehabilitated? (altered functions), how? (substitution, restitution,
      integration, activation, etc.) and when? (in what chronological order should
      these interventions take place and at what point). CONCLUSION: Work with definite
      theoretical models on which to base diagnosis and treatment of psychic function
      would facilitate comparison of results and allow better understanding of the
      working of the normal brain.

PMID- 10893745
TI  - [Training in social skills in patients with acquired brain damage].
AB  - INTRODUCTION: Brain damaged patients have cognitive deficits, behaviour disorders
      and personality changes which affect socio-familial behaviour. Frequently, these
      changes generate considerable disturbance between family members and make it very
      difficult to return to work. OBJECTIVE: We describe a pilot study which led to
      the development and application of a focal rehabilitation programme aimed at
      retraining this group in social skills. PATIENTS AND METHODS: The programme was
      intensive (3 months) and included 6 outpatients (5 men and 1 woman) who took part
      in programmes of neuropsychological rehabilitation after traumatic or vascular
      cerebral lesions (X = 19.2 months after the lesion occurred). The average age of
      the patients was 27.2 years and their average IQ 109.2. Individual and group
      interventions were combined (role-playing, 'make-believe' work, video filming)
      emphasizing particularly the processes of learning without making mistakes and
      the extension of achievements to the natural setting (controlled trials). RESULTS
      AND CONCLUSIONS: We state and describe the relationship between the nature of
      neuropsychological and psychopathological deficits, and the characteristics of
      the limitations in social behaviour. The patients showed a significant reduction
      in the level of anxiety and aggressive behaviour and improvement in consciousness
      of their defects. Some improvement was seen in expressing opinions and emotions,
      and in ability to adapt social conduct to different situations (flexible
      behaviour). Finally we describe the conclusions drawn as to this treatment for
      future review and improvement of the programme.

PMID- 10893746
TI  - [Neuropsychological characteristics of Parkinson's disease].
AB  - INTRODUCTION: Form part of the clinical symptoms of Parkinson's disease. These
      disorders may present in varying degrees: whilst in some patients a clinical
      picture of dementia is seen, in others there are only specific symptoms.
      DEVELOPMENT: In this article we consider three of the most controversial aspects
      currently dominating study of the neuropsychology of Parkinson's disease. The
      first relates to the pathophysiological basis and neurotransmitters involved. The
      second deals with the distinction between subcortical-type and Alzheimer-type
      dementia, and the third with the pathophysiological basis underlying the
      cognitive profile of the subgroups of patients with Parkinson's disease who do
      not present dementia. CONCLUSION: The relation between the factors causing the
      disease, neuropathology, individual variables and the presence of these subgroups
      requires precise systematic investigation of the neuropsychology shown by
      patients with Parkinson's disease.

PMID- 10893747
TI  - [Subacute combined degeneration without anemia].

PMID- 10893748
TI  - [Cerebral abscess in an immunocompetent patient].

PMID- 10893749
TI  - [Acute necrotizing encephalopathy due to influenza A].

PMID- 10893750
TI  - [Sudden paraplegia due to a spinal epidural abscess. A case report].

PMID- 10893751
TI  - [Neurological diagnosis and prognosis: significance of neurophysiological
      findings in traumatic spinal cord lesions].
AB  - The clinical examination of patients with spinal cord injury can be supplemented
      by electrophysiological techniques (somatosensory evoked potentials [SSEP], motor
      evoked potentials [MEP], and electroneuromyographic recordings [ENMG]) to assess
      the extent and severity of a spinal cord injury. An essential advantage of these
      techniques in comparison with clinical examination is that they can also be
      reliably applied in uncooperative patients. These techniques allow early
      prognosis regarding the functional deficit in patients with acute spinal cord
      injury. Recordings of tibial nerve somatosensory evoked potentials and motor
      evoked potentials of the anterior tibial muscle serve to predict the outcome of
      ambulatory capacity, and pudendal nerve somatosensory evoked potentials that of
      bladder function. In tetraplegic patients median and ulnar nerve somatosensory
      evoked potentials and motor evoked potentials of the abductor digiti min. muscle
      may indicate the outcome of hand function at an early stage. The
      electroneuromyographic recordings make it possible to differentiate between the
      proportion of peripheral and central nervous lesion underlying a muscle paresis.
      This is of prognostic value in regard to the development of muscle tone and
      consequently for planning of therapy. The electrophysiological examinations are
      of complementary value in the diagnostic assessment of spinal cord lesions, in
      the prediction of functional outcome, and in monitoring the course of
      neurological deficits. This is helpful for planning and selection of appropriate
      therapeutic approaches within the rehabilitation programme.

PMID- 10893752
TI  - [Intensive care treatment concepts after traumatic spinal cord injury].
AB  - Spinal injuries are caused by strong traumatic impacts, followed not only by a
      local spinal reaction but also systemic involvement. The main problems in the
      early posttraumatic period are haemodynamic instability, pulmonary insufficiency
      and SIRS. In this period multiple risks of secondary injuries to the spinal cord
      or other organs exist and may develop towards life-threatening sepsis, ARDS and
      multi-organ failure. Optimum therapy for spinal injury patients is demanding and
      requires an experienced team for diagnosis as well as primary and secondary care.
      Close cooperation between intensive care and surgery is also important.

PMID- 10893753
TI  - [Traumatic paraplegia: surgical measures].
AB  - Reduction and fixation of unstable spine injuries in patients with neurological
      deficit are the prerequisites for early rehabilitation. Diagnostic procedures and
      surgery in patients with para-/tetraplegia must be performed urgently to avoid
      further neurological damage and ensure recovery. In parallel administration, high
      dose steroids are initiated immediately after admission. In general, unstable
      spine fractures are reduced in a closed or open manner and stabilised. Bony
      fragments occluding the spinal channel are removed and, if necessary, the
      anterior column is reconstructed. Unstable fractures of the cervical spine are
      operated on either from the back and/or anteriorly, although the techniques used
      in the upper cervical spine are quite different from those used in the lower
      cervical spine. Instabilities of the thoraco-lumbar junction are reduced and
      stabilised via a dorsal and/or anterior-lateral approach (transthoracic or
      retroperitoneal). Exact preoperative planning is necessary due to the proximity
      of large vessels and organs, as well as the narrow space for positioning of the
      implants. With early operative stabilisation of the spine paretic/paralysed
      patients can be mobilised immediately and personal care is facilitated. In this
      article the operative techniques are described on the basis of examples chosen
      from 606 patients treated at the Division of Trauma Surgery, University Hospital
      of Zurich from 1992 to 1997. 119 patients (19%) were diagnosed with
      incomplete/complete para-/tetraplegia and 51 with various degrees of neurological
      deficit.

PMID- 10893754
TI  - [Focus on current research: improving the mobility of paraplegic patients].
AB  - Since the first paraplegic centre was established in 1945, life expectancy and
      life quality of paraplegics have considerably improved. However, endeavours to
      enhance the mobility of these patients have been less successful. The most
      promising approach, functional electric stimulation of paralysed muscles, is
      poorly accepted by patients at present because of technical problems. This study
      describes current approaches which may help to improve patients' mobility. A
      central motor lesion is perceived by the patient as a movement disorder of the
      legs, e.g. a gait disorder. Neurological investigation indicates, on the basis of
      exaggerated tendon reflexes and increased resistance of the non-activated leg
      muscles to stretching, that spastic paresis underlies the movement disorder. This
      combination of symptoms and clinical (physical) signs suggests that the
      exaggerated tendon tap reflexes are responsible for muscle hypertonia and the
      latter causes the movement disorder. However, electromyography during movement
      shows that the exaggerated short latency reflexes are associated with loss or
      attenuation of the functionally essential polysynaptic spinal reflexes. In the
      event of impaired supraspinal control there is loss of monosynaptic stretch
      reflex inhibition combined with reduced facilitation of polysynaptic spinal
      reflexes. Development of tension in tonically active calf muscles in patients
      with spastic paresis during gait occurs independently of spinal reflex activity.
      From electrophysiological and histological observations it can be assumed that
      transformation of motor units resulting in simple and less well adapted
      regulation of muscle tone allows movements such as gait. The reduction of muscle
      tone obtained with antispastic drugs is usually associated with paresis and may
      therefore hamper locomotion. Locomotor training represents a new attempt to
      improve the mobility of patients with incomplete paraplegia. It includes
      activation of neuronal circuits within the spinal cord below the level of the
      lesion. In incomplete paraplegics a coordinated leg muscle activation pattern and
      corresponding leg movements can be triggered and trained in patients standing on
      a treadmill with partial weight support. Improvement of training of the spinal
      cord locomotor centre can be expected from triggering of spinal cord reflexes and
      regeneration of spinal tract fibres, which is expected to be possible in the near
      future.

PMID- 10893755
TI  - [Cardiovascular disorders in paraplegic patients].
AB  - While the consequences of damage to the sensorimotor nervous system in spinal
      cord injury are obvious, autonomic dysreflexia often goes unrecognised. Spinal
      cord injury affecting the cord above the fifth thoracic segment involves
      interruption of the connection between brain and sympathetic nervous system and,
      below the level of the lesion, the sacral parasympathetic nervous system. The
      isolated spinal cord continues to function, except for the directly damaged
      segment, but there is no central control. The autonomic nervous system below the
      level of the lesion can trigger severe reactions from the cardiovascular system
      which diminish quality of life and even promote severe morbidity. Autonomous
      malfunction can also have clinical effects in relation to thermoregulation and
      gastrointestinal, genital and urinary tract function.

PMID- 10893756
TI  - [Acute myelopathy and cauda equina syndrome].
AB  - The high incidence of non-specific, benign back trouble often delays the
      diagnosis of specific causes of back pain and thus result in neurological
      deficits. Degenerative abnormalities in the cervical spine may narrow the spinal
      canal and result in acute myelopathy subsequent to minor injuries. Large cervical
      or lumbar disc herniations causing myelon, conus or cauda equina compression are
      rare but must not be overlooked. Spinal metastases may remain unrecognised for a
      long period and lead to the correct diagnosis only after presentation with
      neurological deficits. Acute myelopathy or cauda equina syndrome are indications
      for immediate diagnostic assessment and treatment in a spine centre.

PMID- 10893757
TI  - [Post-inpatient after-care of paraplegic patients: selected internal medicine
      aspects].
AB  - In-hospital rehabilitation of para-/tetraplegic patients is followed by the
      family doctor's long-term surveillance supported by annual checkups in the
      rehabilitation clinic. The family doctor bears a heavy burden of responsibility.
      Loss of sensation may cover a wide range of complications. Most of these
      functional disorders are the consequence of reduced physical activity and a
      disturbed autonomic nervous system. There is a significantly high incidence of
      pulmonary infection, in particular pneumonia and atelectasis, coronary heart
      disease, autonomic dysreflexia, urinary tract infections, kidney stones, renal
      and hepatic insufficiency, gallstones, constipation and ileus, as well as
      decubitus, osteoporosis and so on. Chronic severe pain and spasm also require
      optimum therapy, in view of their potential to reduce quality of life and working
      capacity. This article provides an overview of several relevant problems in
      internal medicine involving diagnosis, therapy and long-tem surveillance of
      patients with spinal cord injuries.

PMID- 10893758
TI  - [Type 2A multiple endocrine neoplasia with cutaneous lichen amyloidosis].

PMID- 10893759
TI  - On dental trauma in children and adolescents. Incidence, risk, treatment, time
      and costs.
AB  - BACKGROUND: Dental trauma occur in childhood and adolescence with consequences in
      time and costs for both patient and family. The scientific knowledge of these
      matters is scarce. For some individuals, dental trauma will result in long, time
      consuming and costly treatments in childhood which will continue into adulthood.
      AIM: The thesis aimed to increase the knowledge of incidence, risk, treatment,
      time and costs spent on dental traumas to primary and permanent teeth in children
      and adolescents. MATERIAL AND METHOD: The material for the studies emanated from
      the county of Vastmanland, Sweden, and the municipality of Copenhagen, Denmark,
      and from a Swedish nation-wide material (Folksam). The material was collected
      from accident reports, dental files, dental trauma forms, questionnaires and
      telephone interviews. Descriptive, prospective and analytical methods were used.
      A classification of uncomplicated and complicated dental traumas was presented.
      RESULTS: The incidence of dental trauma to boys was higher, compared to girls, in
      the county of Vastmanland in almost all age groups. For both sexes, the first
      years in life and the first years in school were the most accident prone periods
      with incidence twice as high as the average incidence for all children and
      adolescents in the county. Every third trauma was complicated with injuries to
      the pulp or periodontal ligaments. Every second patient with a dental trauma to
      permanent teeth suffered from multiple dental trauma episodes (MDTE) during a
      period of 12 years. In almost every second patient with MDTE, at least one of the
      affected teeth had sustained repeated trauma episodes. The risk of sustaining
      MDTE increased when the first trauma episode occurred in the age interval of 6
      10, compared to 11-18 year olds. During a 12-year period, treatment times for
      complicated traumas were 2.0 and 2.7 times higher for primary and permanent
      teeth, respectively, compared to corresponding values for uncomplicated traumas.
      On average, direct time (treatment time) represented 11% and 16% of the total
      time, while the direct costs (health care service, transport, loss of personal
      property and medicine) represented 60% and 72% of the total costs of traumas to
      primary and permanent teeth, respectively, during a 2-year period for cases of a
      nation-wide material. CONCLUSION: Dental traumas are frequent and some
      individuals are injured several times. Besides treatment time, efforts from the
      family are substantial in time and costs. Parameters such as degree of severity,
      access to treatment and place of injury are of major importance to both patient
      and family and should be considered when calculating time and costs of dental
      trauma in children and adolescents.

PMID- 10893760
TI  - [Analysis of the needs for diagnosis and therapy of tobacco dependence in
      Austria].
AB  - In Austria we find 2.3 Mio. tobacco users (29% of the population). 1.3 Mio. are
      dissonant smokers, they want to stop (18%) or reduce (37%) tobacco consumption.
      The assumption that 10% of dissonant smokers (130,000 tobacco users) need a
      diagnosis and therapy leads to a bottleneck: 130,000 patients versus 20
      therapists. Demanded consequences of this disproportion are training for health
      care workers, implementation of diagnosis and treatment, financing and refunding.
      Diagnosis and therapy of tobacco dependence should be offered in highly
      specialised organisations such as the prototypical Nicotine Institute in Vienna,
      in hospitals and in primary health care.

PMID- 10893761
TI  - [Psychiatric complications of pharmacotherapy--a review].
AB  - Various commonly used drugs with somatic indications may give rise to a host of
      partially serious psychiatric side-effects. This overview details important
      prescribed drugs of daily use and their psychiatric complications. The problems
      of elderly patients are particularly considered. Also, polypharmacy will be given
      special attention.

PMID- 10893762
TI  - [Psychotherapeutic intervention with families after multiple suicides].
AB  - Every suicide must be seen as tragedy. The amount of that tragedy is sometimes
      extraordinary. For example, when families experience multiple suicides. The
      consequences should be, by enhanced postvention to prevent a PTSD-like syndrome
      and to consider more often the administration of SSRI in persons bereaved by
      suicide. When manifest phases are prevalent, substances like lithium are
      recommendable. The importance of psychotherapy and psychosocial intervention has
      to be emphasized.

PMID- 10893763
TI  - ["Myocardium in hibernation"--implications for clinical medicine].
AB  - Myocardial infarction is one of the leading causes of heart failure. Medical
      therapy of heart failure is effective in reduction of morbidity and mortality. In
      spite of intensive pharmacological and non-pharmacological treatment, prognosis
      of advanced heart failure remains poor. Fibrinolytics and other adjuvant medical
      strategies have improved prognosis of acute myocardial infarction with a
      significant reduction in mortality and morbidity. 40% of myocardial segments
      involved in acute ischemia during myocardial infarction show characteristics of
      postischemic functional disorder and contraction abnormalities despite
      reperfusion. Recovery can be observed in the following period spontaneously or
      after revascularisation procedures when chronic ischemic myocardium can be
      detected. Presence of viable jeopardized myocardium worsens prognosis and overall
      outcome in patients with myocardial ischemia and impaired left ventricular
      function. Revascularisation procedures improve angina functional class, symptoms
      from heart failure, exercise capacity and survival in patients with impaired left
      ventricular ejection fraction in the presence of severe coronary artery stenoses
      and viability of myocardial segments with ischemia-induced contractile
      dysfunction.

PMID- 10893764
TI  - [Progressive hearing loss].
AB  - Progressive sensorineural hearing loss (SNHL) is defined as hearing loss of
      unknown etiology with fairly high-speed progression. Its diagnostic criteria
      consist of the following: that it is 1) progressive, 2) with bilateral
      involvement, and 3) of unknown etiology. Due to recent advances in diagnostics,
      imaging and management, SNHL has gained much interest from otologists in the last
      few years. They provide new insight into the physiology and pathophysiology of
      hearing. SNHL which is sudden in onset, fluctuating, and/or progressive
      complicates medical management, hearing aid selection, and individualized
      educational planning for a hearing-impaired patient. Existing hypotheses on the
      etiology of SNHL are judged on experimental, clinical, laboratory and
      radiological evidence. Cardiovascular and rheologic diseases, hereditary
      disorders, immunological phenomena, infections, environmental causes like noise,
      ototoxic drugs and industrial substances and systemic maladies must be included
      in the diagnostic reflections. Potential concepts of treatment include rheologic
      medications and corticosteroids. Hearing aids and timely cochlear implant
      operation are further possible forms of treatment.

PMID- 10893765
TI  - [Ethical aspects of medical practice in AIDS].

PMID- 10893766
TI  - [Changes in the profile of HIV-positive patients. What has happened in the last 5
      years?].
AB  - OBJECTIVE: To evaluate possible changes in the social, cultural and economical
      profile of our HIV infected patients appearing during the last five years and
      their potential impact on incidence, prevention, and follow-up of HIV infection.
      METHODS: We conduce a retrospective analysis of demographic, sociocultural,
      clinical and therapeutic characteristics of two groups of HIV infected patients
      reaching for the first time a level of 300 CD4 or less either in 1992 or in 1997.
      RESULTS: 55 patients with a mean age of 33 years (68% male 32% female) were
      studied. No differences were found in sexual behavior, HIV status of sexual
      partner, cultural level, risk practice, VHB or YHC seroprevalence. Attempts al
      drug quitting in 1992 were made individually and through institutional programs
      in 1997. Significant differences were found in the number of visits to the
      outpatient clinic the previous 36 months, and in de number of drugs (1.5 versus
      3.5 P < 0.0001). Antirretroviral drugs were use in 62% of our 1992 patients and
      in 86% of the 1997 group (p < -0.02). CONCLUSIONS: The sociocultural and
      demographic profile has not changed in our environment in the last five years.
      However patients were identified later and followed less regularly at our clinic
      five years ago. Institutional methadone programs are the method or choice in our
      current patients for stopping illicit drug use. Finally treatment intensity has
      dramatically increased in our patients parallel to the growing therapeutical
      arsenal in this field.

PMID- 10893767
TI  - [Clinico-epidemiologic manifestations of progressive multifocal
      leukoencephalopathy in patients with acquired immunodeficiency syndrome (AIDS)].
AB  - BASIS: Severely immunosuppressed patients, including those with AIDS in advanced
      stage, can suffer opportunistic infections, between them PML. The purpose of this
      study is to determine epidemiological, clinical and neuroradiological parameters
      of HIV infected patients diagnosed of PML. METHOD: Retrospective review of
      clinical histories and clinical as well as radiological characteristics, of seven
      patients diagnosed of AIDS and PML in the Infectious Diseases Unit of our center
      between January 1990 and December 1997. RESULTS: Seven patients out of 1093 HIV
      infected patients were diagnosed of PML (0.76%). All of them were male,
      intravenous drug users, with a mean age of 32.1 years. Five patients were
      diagnosed before 1994. In four cases PML was the first opportunistic infection.
      The mean survival time was 119 +/- 82.2 days (27-231 days). At the moment of
      diagnosis four patients (57.1%) showed cerebellar symptoms, three (42.8%) sensory
      deficits and two (28.5%) cognitive dysfunction. There were multiple neurological
      symptoms in five cases. The mean CD4 cell count was 63.4 cells/mm3. None of the
      patients showed other concomitant opportunistic infections neither disturbances
      of cerebrospinal fluid (CSF). CT and NMR showed typical lesions in frontal lobe
      and cerebellum in four patients. Other affected areas were occipital and parietal
      lobe, basal ganglia and brain stem. The diagnosis of PML was established by
      clinical and neuroradiological criteria in six patients and by autopsy in one
      patient. CONCLUSIONS: The diagnosis of PML in HIV infected patients can be made
      by clinical and neuroradiological criteria. In the last years, and probably due
      to the new antiretroviral agents, it has been observed a decrease of the PML
      incidence in these patients. Nevertheless its prognosis is still dreadful and at
      present there is no specific curative treatment.

PMID- 10893768
TI  - [Alkaline phosphatase isoenzymes in serum and bronchoalveolar lavage from
      patients with bronchopulmonary disease].
AB  - OBJECTIVE: In this study, we are looking at the principal isoenzymes of alkaline
      phosphatase (ALP), as injury markers of cellular membranes from bronchial
      epithelium, in 80 patients diagnosed with bronchopulmonary pathology from
      different ethology, using serum samples and bronchoalveolar lavage fluid (BAL).
      METHOD: Patients were grouped according to age as following: 26 preterm neonates
      suffering respiratory distress syndrome requiring mechanical ventilation; 32
      children ranging from 2 to 12 years old, and 22 adults (30-65 years old) examined
      by bronchoscopy for the purpose of diagnosis. Results obtained from all
      pathological groups were compared with a control group showing similar
      characteristics. Isoenzymes were separated by electrophoresis on agarose gel and
      were quantified by desitometry. Total protein was measured in BAL; ALP activity
      was expressed in UI/mg x 10-3 of protein. RESULTS: We found that macromolecular
      ALP fraction was significantly increased in the serum of neonates with distress
      (p < 0.01), in the patients 2-12 years and adults affected by pulmonary pathology
      (p < 0.001). The electrophoresis of ALP isoenzymes showed a unique isoenzymatic
      band corresponding with its macromolecular fraction in the BAL fluid.
      CONCLUSIONS: We conclude that increased macromolecular fraction of alkaline
      phosphatase found in the serum of patients diagnosed with respiratory problems
      could have its origin in damaged pulmonary tissue.

PMID- 10893769
TI  - [Usefulness of carcinoembryonic antigen and other markers in patients with
      hemoptysis].
AB  - OBJECTIVE: We have examined the carcinoembryonic antigen (CEA) and other tumor
      markers (immunoglobulins, CA 19.9, LDH, alpha-fetoprotein and alpha-1
      antitrypsin) with the purpose of recognize their utility in patients with
      hemoptysis and patients older than 45 years with a positive smoking history and
      hemoptysis. METHODS: We measured, analyzed and compared these markers in 336
      patients with a known etiology of hemoptysis divided in group I (malignant
      etiology) with 101 cases (30.1%) and II (nonmalignant) with 235 cases (69.9%) (p
      < 0.001). RESULTS AND CONCLUSIONS: The values of CEA, LDH and CA 19.9 were
      increased in group I, without differences when we compared immunoglobulins (G, A
      and M), alpha-fetoprotein and alpha-1-antitrypsin in both groups. CEA and LDH
      were increased significantly according to the disease extent in nonsmall cell
      lung carcinoma. Smokers had an increased CEA only in group II. Plasma values of
      CEA higher than 5 ng/mL meant that the likelihood of bronchial carcinoma was
      high. Our markers proved to be more specific and with a high positive or negative
      predictive values than sensitives. These results would suggest that they are not
      of great help for early diagnosis of lung cancer, however an increase of CEA, LDH
      and CA 19.9 plasma concentrations could suggest with high probability a bronchial
      carcinoma, improving their diagnostic sensibility when we used them in
      combination.

PMID- 10893771
TI  - [Late diagnosis of Turner syndrome: therapeutic implications].
AB  - We report the case of a patient with Turner's syndrome, whose special peculiarity
      is that its clinical signs have gone unnoticed despite the presence of several
      morphological features and functional disorders which must have induced it
      precociously. It's about a 58 years old patient with an aortic metalic valve in
      treatment with dicumarinics, who came to emergencies with a severe anemic
      syndrome because of a peptic ulcer propitiated by the hypoprotrombinaemia. In the
      physical examination some typical signs of the syndrome were detected. The
      karyotype verified the existance of Turner (45X0). We insist on the need of an
      early diagnosis, in order to prevent the short stature and to offer a
      satisfactory sexual development, and we include an actualization of the different
      approachments in the therapy and management of the disease.

PMID- 10893770
TI  - [Malignant prolactinoma with intra- and extracranial metastasis: clinico
      radiologic study].
AB  - Malignant prolactinomas are very rare pituitary neoplasms which can be identified
      not from the hystopathologic nor neuroimaging aspects but only retrospectively
      from the presence of distant metastases. A 32-year-old male patient was diagnosed
      of a pituitary prolactinoma because of bitemporal hemianopsia on the basis of
      cranial MRI aspect and raised blood prolactin level. Visual signs improved under
      bromocriptine treatment but after surgical and X-ray therapies patient developed
      paralysis of V and XII left cranial nerves and suffered from medulocerebelous
      angle, vertebrae, spinal epidural space, lung, liver, suprarenal and femoral
      metastases. Patient died 3 years after the diagnosis time. Prolactin levels
      raised 2000 ng/ml. This is the first case of malignant prolactinoma described in
      the spanish literature and the more large one in number of metastatic
      localizations between the malignant prolactinomas from the literature. These kind
      of neoplasms can be partially ameliorated under X-ray and bromocriptine treatment
      but there is not, by the moment, a curative chemotherapy.

PMID- 10893772
TI  - [Bullous emphysema and neurofibromatosis].
AB  - Clinical and image findings in a 43 year-old smoker man with advanced lung
      bullous emphysema and von Recklinhausen's neurofibromatosis are presented.
      Bullous emphysema and subpleural neurofibromas were detected in a chest computed
      tomographic study. The possible association or independence of these two
      conditions is discussed.

PMID- 10893773
TI  - [Solid liver mass. Studies with nuclear medicine].
AB  - We present the case of a 23 year old female with two incidentally detected
      hepatic mass that have not clinically o radiologically specific findings. Nuclear
      medicine tracers, including colloids and hepatobiliary agents showing the
      characteristic findings of focal nodular hyperplasia: Hypervascularization,
      normal uptake of colloids, accumulation of hepatobiliary tracer and hot spots due
      to the retention of this tracer during the clearance fhase. The patient was
      underwent hepatectomy. The examination of surgical specimen revealed focal
      nodular hyperplasia. The scintigraphic studies could be an useful tool in the
      noninvasive diagnosis of liver masses.

PMID- 10893774
TI  - [Clinical manifestations, diagnosis and treatment of Haemophilus influenzae
      infection].
AB  - Haemophilus influenzae is a small, nonmotile, non-spore-forming bacterium, and a
      strict parasite of humans found principally in the upper respiratory tract. The
      production of capsule is of major significance to clinicians since it is an
      important virulence factor. We described six antigenically distinct capsular
      types, designated a-f. Spread from one individual to another occurs by airborne
      droplets or by direct contagion with secretions. Haemophilus influenzae produces
      at least two factors that inhibit the ciliary activity of human epithelial cells
      in vitro. One of this has been shown to be lipopolysaccharide and the other
      factor is of low molecular weight, most likely a heat-stable glycopeptide. Type b
      strains are distinguished by the production of capsular polysaccharide composed
      of repeating units of ribosyl-ribitol phosphate, account for greater than 95
      percent of systemic infections in children. Two contrasting patterns of
      Haemophilus influenzae disease can be identified. The first and the most serious
      in its consequences is invasive infection such as meningitis, septic arthritis,
      epiglottitis, and cellulitis in which bacteremia is a prominent feature; these
      infections are usually caused by type b strains and occur in young children. The
      second category includes less serious but numerically more common infections,
      that occur as a result of contiguous spread of Haemophilus influenzae within the
      respiratory tract; e.g. otitis media, sinusitis. These latter infections are
      usually, but not invariably, caused by unencapsulated strains. A provisional
      diagnosis of meningitis, epiglottitis, facial cellulitis, or septic arthritis
      will usually be prompted by the history and clinical findings. Confirmation
      requires microbiologic studies. Cultures of blood, CSF and other normally sterile
      fluids are diagnostic and therefore under the appropriate circumstances
      mandatory. Whenever feasible, specimens obtained for culture should also the gram
      strained. Detection of capsular antigen in serum, CSF or concentrated urine using
      immunoelectrophoresis, latex agglutination or enzyme linked immunosorbent assay
      may be diagnosed and can be found in up to 90 percent of culture proved cases of
      meningitis. Without treatment, infection due to Haemophilus influenzae can be
      rapidly fatal, particularly by meningitis and epiglottitis. There is currently a
      trend to use certain parenteral third generation cephalosporins as initial
      therapy when lifethreatening Haemophilus influenzae infection is known or
      suspected in children beyond the neonatal period, commonly used agents included
      cefotaxime or ceftriaxone. Antibiotic therapy is only one facet of the management
      of the child with Haemophilus influenzae infection, and critical attention must
      also be given to supportive therapy. In the ambulatory setting, ampicillin or
      amoxicillin for 10 days is often satisfactory for the less severe Haemophilus
      influenzae infections. Cephalosporins are often chosen for treatment of adults,
      with pneumonia when Haemophilus influenzae is documented.

PMID- 10893775
TI  - [Hypergammaglobulinemia D syndrome].
AB  - The hyperimmunoglobulinemia D syndrome is characterized by early onset of attacks
      of periodic fever and an elevated serum polyclonal Ig D (> 100 U/ml). Symptoms
      during attacks include joint involvements (arthralgia/arthritis), skin lesions,
      swollen lymph nodes, headache and abdominal complaints (vomiting, diarrhea and
      pain). The ethiopathogenia is unknown. It is transmitted by autosomal recessive
      inheritance. The hyperimmunoglobulinemia D syndrome should be distinguished from
      other periodic febrile syndroms such as systemic-onset juvenile rheumatoid
      arthritis, CINCA syndrome, FADA syndrome, familial mediterranean fever and adult
      onset Still disease. There is no therapy for the syndrome but the prognosis is
      good because the frequency and severity of the attacks tends to diaeminish with
      age.

PMID- 10893776
TI  - [A supposedly paraneoplastic cerebellar syndrome].

PMID- 10893777
TI  - [Blood macroamylase and celiac disease].

PMID- 10893778
TI  - [Splenic infarction as presentation form of antiphospholipid syndrome].

PMID- 10893779
TI  - [Deep venous thrombosis: unusual manifestation of idiopathic retroperitoneal
      fibrosis].

PMID- 10893780
TI  - [Endocarditis caused by Erysipelothrix rhusiopathiae].

PMID- 10893781
TI  - [Sneddon syndrome with cardiovascular involvement].

PMID- 10893782
TI  - [Complete heart block induced by intravenous metoclopramide].

PMID- 10893783
TI  - [Thyrotoxic periodic paralysis: unusual complication of a frequent disease].

PMID- 10893784
TI  - [Prognosis of HIV-infection. Let's put ourselves in all the cases].

PMID- 10893785
TI  - [Cutaneous vasculitis caused by ciprofloxacin].

PMID- 10893786
TI  - Ergonomic evaluation of antenatal ultrasound testing procedures.

PMID- 10893787
TI  - An ergonomic approach to analyzing workplace accidents.
AB  - By looking for root causes for accidents and incidents through an ergonomic
      evaluation of the task demands, environment, organizational factors, and workers'
      capabilities to perform tasks, identification of interventions can be made to
      reduce the risk for injury in most situations. Small changes can make significant
      differences and give a clearer understanding of how the workplace environment,
      management policies, individual capacities, and job demands impact the safety and
      health of individuals on the job.

PMID- 10893788
TI  - Control of spotting chemical hazards in commercial drycleaning. National
      Institute for Occupational Safety and Health.

PMID- 10893789
TI  - Silica overexposure in sandblasting.

PMID- 10893790
TI  - Manganese dioxide exposures and respirator performance at an alkaline battery
      plant.
AB  - Two industrial hygiene studies were conducted at an alkaline battery plant to
      evaluate worker exposures to manganese dioxide particulate and the effectiveness
      of filtering facepiece respirators. The work areas studied included the plant's
      powder-processing tower and press rooms where manganese was blended, compacted
      with graphite, and inserted into battery cans. Full-shift personal breathing zone
      monitoring was conducted to estimate manganese dust exposures of press operators,
      mechanics, and material handlers. In-facepiece and personal breathing zone air
      sampling pairs were also collected using a program protection factor protocol to
      estimate the protection provided by the respirators. Particle size evaluations
      were made using nylon cyclones and Marple personal multi-stage impactors. All
      samples were analyzed for manganese by inductively coupled argon plasma, atomic
      emission spectroscopy via NIOSH analytical method 7300 utilizing a modified acid
      digestion procedure. Fifty-four, full-shift, time-weighted average (TWA)
      exposures to total manganese ranged from 0.1 to 5.4 milligrams per cubic meter
      (mg/m3); worker exposures were substantially lower during a follow-up study due
      to engineering control improvements. Concurrent area sample comparisons of total
      and respirable manganese revealed that the respirable particulate mass fractions
      ranged from 6 to 32 percent, and mass median aerodynamic diameters determined
      from personal breathing zone air samples were mostly greater than 10 micrometers.
      Fifteen respirator performance evaluations were conducted using Moldex 2200
      respirators fitted with 25 millimeter cassettes and light weight sampling probes.
      Protection factors ranged from 5 to 220, with a geometric mean and standard
      deviation of 31 and 2.97, respectively. The 5th percentile protection factor
      estimate was 5, as calculated from the protection factor distribution for this
      sample set. In 1995, the American Conference of Governmental Industrial
      Hygienists (ACGIH) lowered the elemental and inorganic manganese dust Threshold
      Limit Value (TLV) from 5 mg/m3 to 0.2 mg/m3 to address adverse pulmonary and
      central nervous system effects and male infertility. Although most personal
      breathing zone concentrations were above 0.2 mg/m3, none of the in-facepiece
      concentrations exceeded this concentration. Parkinson's-like symptoms have been
      reported in the literature for high manganese dust and fume exposures, but the
      importance of low dust exposures for producing neurological effects is uncertain.

PMID- 10893791
TI  - Using water sprays to improve performance of a flooded-bed dust scrubber.
AB  - Supplemental water sprays were placed along the sides of a continuous mining
      machine to improve suppression and confinement of the dust cloud under the
      cutting boom to reduce downwind dust levels. Using a full-scale mock-up of a
      continuous mining machine, preliminary work showed that these side sprays
      improved suppression of the dust cloud and redistributed this cloud under the
      cutting head. This led to reductions in dust levels around the machine and in
      down-wind airways for some positions of the mining machine. This testing also
      showed that side spray effectiveness was influenced by the distance from the
      fresh air ventilation device to the cutting surface, termed the ventilation
      setback distance. These sprays produced larger reductions in machine and return
      dust levels at smaller setback distances than at larger setback distances. These
      side sprays then were installed in similar locations on a mining machine at an
      underground coal mine operation to evaluate their effectiveness for improving
      suppression and capture of dust by the flooded-bed dust scrubber. Although
      sampling could not be conducted successfully in the return, sampling around the
      mining machine and at the machine operator showed that dust levels decreased with
      use of these sprays. Further analysis showed that these sprays were most
      effective at the smaller setback distances, a result confirmed by full-scale
      laboratory testing.

PMID- 10893792
TI  - Particulate penetration of porous foam used as a low flow rate respirable dust
      size classifier.
AB  - Porous foam has been used as a material for classification of particulate matter
      into various size fractions. The penetration characteristics of a nominal 90
      pores per inch porous foam were studied at various flow rates, face velocities,
      and foam plug diameters and compared to the aerosol penetration of a 10 mm Dorr
      Oliver cyclone operated at 1.7 L/min. Poly-dispersed triethanolamine spheres were
      classified through porous foam plugs and the resulting penetration was determined
      using an aerodynamic particle sizer. Results showed that for a given plug
      diameter, as face velocity increased from 26 to 39 cm/sec, the 50 percent cut
      point decreased from 4.5 to 3.8 microns. Furthermore, as the diameter of the plug
      increased from 4 to 12 mm, the 50 percent cut points were similar to other plug
      diameters at equivalent face velocities. The best match to the 1.7 L/min cyclone
      penetration characteristics occurred at a flow rate of 250 ml/min through a 25 mm
      by 4 mm diameter section of 90 pore per inch foam. Because of the need to provide
      short-term or real-time estimates of worker respirable dust exposure, porous foam
      may be a viable classification media for a low flow rate, disposable respirable
      dust sampler for use in the coal mining industry.

PMID- 10893793
TI  - Deaths from external causes of injury among construction workers in North
      Carolina, 1988-1994.
AB  - Records from the Office of the North Carolina Chief Medical Examiner were used to
      describe 3955 deaths, both on and off the job, between 1988 and 1994 from
      external causes of injury (E-codes) among individuals whose usual occupation was
      in the construction trades. For the calculation of rates, population sizes were
      estimated using 1980 and 1990 census data. Deaths from injuries occurred at an
      average rate of 226 per 100,000 population; 213 per 100,000 for non-work-related
      fatalities and 13 per 100,000 for work-related fatalities. Overall, deaths were
      most often from guns or motor vehicle accidents. Work-related deaths were most
      often caused by motor vehicles (21%); falls (20%), most commonly from roofs or
      scaffolds; and machinery (15%), electrocutions (14%), and falling objects (10%).
      Three major causes of work-related motor vehicle accidents were identified
      including injuries to pedestrians in highway work zones and in backovers on
      construction sites, and injuries to drivers caused by shifting loads while
      transporting construction materials. The circumstances surrounding deaths
      involving scaffolding document the need for training and safety procedures for
      erecting, moving, and disassembling scaffolds, but also for safe work practices
      on scaffolds. Training and safety procedures to avoid electrocutions must involve
      workers who are not in the electrical trades, as these deaths often occurred
      among individuals who were not electricians or linemen. Significant differences
      were observed in the proportion of victims having elevated blood-alcohol levels
      depending on whether the injury was work-related; 57 percent of victims were
      impaired at the time of fatal non-work-related injuries compared to 5 percent of
      work-related injuries. Interventions to treat and prevent alcohol abuse among
      construction workers could have a significant public health impact in the
      prevention of premature death from injury, particularly outside the workplace.

PMID- 10893794
TI  - Development of an eight-hour occupational exposure limit for beryllium.
AB  - This article recommends an 8-hour occupational exposure limit (OEL) for
      beryllium. It responds to growing concerns about the continuing incidence of
      chronic beryllium disease despite the long-standing OEL for beryllium: 2
      micrograms of beryllium per cubic meter of air (microgram/m3), 8-hour time
      weighted average (TWA). Current 8-hour TWA beryllium OELs are not based on
      chronic beryllium disease toxicology and an increasing number of studies report
      incidence of chronic beryllium disease at exposure levels apparently below 2
      micrograms/m3. The experience of the beryllium-exposed population of Lorain,
      Ohio, in the late 1940s, and the ambient air regulatory standards derived from
      that event provide evidence that establishing a protective level is possible.
      These levels are used as the basis for a new recommended beryllium exposure
      standard. A correspondingly protective 8-hour TWA level of 0.1 microgram/m3 has
      been derived, which, for commonly encountered workplace conditions (in terms of
      geometric standard deviation and percent-compliance), should provide long-term
      mean exposure protection comparable to that received by the unaffected Lorain
      subpopulation and provided by the Environmental Protection Agency (EPA) ambient
      standard. It is concluded that an exposure limit of 0.1 microgram/m3 combined
      with exposure monitoring to assure a high rate of day-to-day compliance would
      provide better control of both long-term mean exposure levels and short-term
      levels than do current occupational exposure limits. The health data available,
      while certainly not conclusive, support further reductions in exposure levels to
      help minimize the incidence of chronic beryllium disease.

PMID- 10893795
TI  - Ultrastructural features of the fat body and oenocytes of Rhinocricus padbergi
      Verhoeff (Diplopoda, Spirobolida).
AB  - The fat body of the diplopod Rhinocricus padbergi is located in two preferential
      areas of its body: a) immediately below the tegument, denominated parietal, and
      b) filling the body cavity, close to the viscera, mainly the ovaries and
      alimentary canal, denominated perivisceral. Ultrastructurally, its cells, the
      adipocytes, presented varied morphology and contained organelles indicating that
      they are cells that mainly produce and store lipids and proteins. The presence of
      cells similar to the oenocytes found in insects was observed for the first time
      in diplopods, associated to the fat body of R. padbergi. Our observations suggest
      that this tissue probably maintains activity cycles, since the presence of cells
      undergoing apoptosis was detected.

PMID- 10893796
TI  - Correlative microscopy of cerebellar Golgi cells.
AB  - The cerebellar Golgi cells of mouse, teleost fish, primate and human species have
      been studied by means of light and Golgi light microscopic techniques, confocal
      laser scanning microscopy, slicing technique, ethanol-cryofracturing and freeze
      fracture methods for scanning electron microscopy and ultrathin sectioning and
      freeze-etching replicas for transmission electron microscopy. The Golgi cells
      appeared in the granular layer as polygonal, stellate, round or fusiform
      macroneurons surrounded by the granule cell groups. They exhibited ascending
      dendrites toward the molecular layer and horizontal dendrites and a short beaded
      axonal plexus confined to the granular layer. Scanning electron microscopy
      revealed their three-dimensional neuronal geometry and smooth outer surfaces.
      Freeze-fracture method for SEM showed the stereospatial cytoplasmic arrangement
      of endoplasmic reticulum, cell organelles and nuclear envelope. By means of
      transmission electron microscopy the asymmetric synaptic connections of Golgi
      cell horizontal dendrites--with mossy fiber rosettes at the cerebellar glomerulus
      -and of Golgi cell axons--with granule cell dendrites at the periphery of
      glomerular region--were identified. At the molecular layer, Golgi cell ascending
      dendrites exhibited short neckless spines establishing asymmetric contacts with
      granule cell axons or parallel fibers. Shaft asymmetric axodendritic and
      axospinodendritic contacts between Golgi cell dendrites and climbing fibers were
      also found in the molecular layer.

PMID- 10893797
TI  - Quantitative ultrastructural changes induced by sucrose administration in the
      pancreatic B cells of normal hamsters.
AB  - We have previously reported that young male Syrian hamsters receiving a sucrose
      rich diet presented increased B-cell replication rate and size. The aim of the
      present study was to analyze, under the same experimental conditions, the
      ultrastructural changes in B cells. For this purpose, young male Syrian hamsters
      were fed with a commercial diet and 10% sucrose in their drinking water (S group)
      while the control group (C) received the same diet and tap water, for 5 weeks.
      Samples of the pancreas removed after that period were processed for the
      immunohistochemical identification of B cells as well as for measuring several
      ultrastructural parameters. S hamsters showed higher serum insulin levels, while
      similar serum glucose values were obtained in animals from both groups. The B
      cells from S group exhibited lesser number of dense secretory granules at
      expenses of an increase of the pale ones, increased number of both exocytosis
      profiles and fusion-granule images, as well as enlargement of the intercellular
      space and mitochondrial area. Marked expansions of this space, limited by
      junctional complexes, were observed between adjacent B cells. These results would
      indicate that sucrose administration to normal hamsters not only increases the
      pancreatic B-cell mass but also induces measurable subcellular changes in the
      individual B-cell characteristic of an enhanced secretory activity. The present
      model would represent a useful tool for testing strategies in preventing the
      damage or promoting the recovery of the pancreatic B cells.

PMID- 10893798
TI  - Comparative study of the ultrastructure and secretory dynamic of hypopharyngeal
      glands in queens, workers and males of Scaptotrigona postica Latreille
      (Hymenoptera, Apinae, Meliponini).
AB  - The secretory cycle of hypopharyngeal glands (HPGs) in Scaptotrigona postica
      resembles that of Apis mellifera: in newly emerged workers the HPGs are in
      prefunctional state, their maximum development happens in the nurse workers and
      in forager workers they show signs of reabsorption. In S. postica these glands
      are also present in queens and males where they are more developed in newly
      emerged individuals. The ultrastructural features of the HPG secretory cycle in
      workers of S. postica and A. mellifera are alike: granular endoplasmic reticulum
      well developed, large secretion masses around the intracellular canaliculus in
      nurse workers and extensive degenerative structures in forager workers. Then it
      is suggested that the HPG secrete similar substances in both species. A second
      secretory cycle seems to occur in early foragers, may be with production of
      enzymes. The role of the HPGs in queens and males remains unknown but one
      possibility is enzyme production.

PMID- 10893799
TI  - Effects of alpha-difluoromethylornithine on the cyclin A expression in Hep-2
      cells.
AB  - DFMO is an irreversible inhibitor of ornithine decarboxilase (ODC), the key
      enzyme in mammalian polyamine biosynthesis. The goal of this study was to
      determine the effects of DFMO on the expression of cyclin A at different stages
      of the cell cycle of Hep-2 cells. The cell cycle analysis, done by measuring the
      incorporation of thymidine in the cell DNA, revealed that DFMO produced a lower
      and constant level of that incorporation; this effect is probably due to the
      incapacity of the cells to culminate the phase S of the cell cycle. The
      expression of cyclin A increased in the phases S and G2 in control cells, almost
      disappearing in phase M. However, in DFMO treated cultures, the expression of
      cyclin A was increased in M and this effect remained still after 48 h treatment.
      We conclude that polyamines could exert an effect on the cyclin destruction
      mechanism, and the depletion caused by DFMO would alter this mechanism.

PMID- 10893800
TI  - Plant regeneration of Ilex paraguariensis (Aquifoliaceae) by in vitro culture of
      nodal segments.
AB  - In vitro regeneration of complete plants from nodal single bud segments of "yerba
      mate" (Ilex paraguariensis St. Hil.) was studied under defined nutritional and
      environmental conditions. Nodal segments harvested from actively growing shoots
      of conventionally raised plants were cultured on nutrient medium with the mineral
      salts and vitamins of Murashige and Skoog medium at 1/4 strength, supplemented
      with various concentrations of sucrose and 6-benzyladenine (BAP). Shoot
      regeneration from explants of both young (2 years old) and adult (20 years old)
      mother plants were readily achieved in the medium supplemented with 0.04-0.09 M
      sucrose with or without BAP. As many as 60-65% of the nodal segments cultured
      formed shoots. Rooting of regenerated shoots was observed in 50% of the explants
      harvested from young plants, whereas 25% of the explants rooted when the nodal
      explants were harvested from adult plants. The best rooting induction was
      achieved on 1/4 strength MS medium with vermiculite as the substrate and
      supplemented with 1-1.5% IBA (indolebutyric acid) and 1-2% PPZ (3-methyl-1-phenyl
      2 pyrazolin-5-one). Plantlets were successfully transferred to soil.

PMID- 10893801
TI  - Calcium and boron for in vitro rooting of Nothofagus nervosa.
AB  - Several mineral compounds influence adventitious rooting, and those containing
      boron and calcium, play an important role. They are associated to the enzyme
      regulation, cell division, cellular metabolism (induction stage) and roots
      enlargement (expression stage). The aims of this work were to study the variation
      of the endogenous calcium and boron concentrations along the rooting, and
      determine their optimal concentrations in the rooting basal medium of Nothofagus
      nervosa. Significant variation in endogenous calcium concentrations was detected
      along the rooting phase, strongly correlated with rhizogenesis phenomenons and
      linked to total peroxidase variation as cited elsewhere. Calcium and boron
      concentrations in the basal medium significantly affected the rooting. Treatment
      containing 60 mg.L-1 Ca and 1 mg.L-1 B produced root formation in fewer days than
      other combinations. The variation of these nutrient concentrations in the medium
      is a useful tool to improve microcutting rooting. Roots are obtained earlier and
      in a shorter period of time, finally resulting in more homogeneous microplants
      with a better developed rooting system.

PMID- 10893802
TI  - In vitro propagation of Berberis buxifolia Lam.
AB  - Berberis buxifolia is a native shrub of Patagonia with a great importance due to
      its crop production as soon its medicinal and tinctorial applications. The aim of
      this work was to develop a protocol for in vitro propagation of B. buxifolia,
      with special emphasys on the rooting stage. The culture of the explants on
      Murashige and Skoog (1962) medium added with 0.55 microM BA allowed to attain a
      multiplication rate of 1:4.7 at day 63. Rooted shoots were obtained on Murashige
      and Skoog medium with half strength of macronutrient salts. The culture of the
      shoots with a period of 4 days of darkness at the beginning of the rooting, on a
      medium with 1.25 microM IBA for 7 days, followed by a IBA free medium until day
      28, allowed to attain 80% rooting. These results show that B. buxifolia can be in
      vitro propagated.

PMID- 10893803
TI  - Sonication of cell extracts improves yield of p53 by immunoblotting.

PMID- 10893804
TI  - Antibiotic prophylaxis.

PMID- 10893805
TI  - Inhalation sedation.

PMID- 10893806
TI  - 1999 BDA Heathrow Timings inquiry.

PMID- 10893807
TI  - PlayStation lip.

PMID- 10893808
TI  - Reading the right research.

PMID- 10893809
TI  - Reader's interpretation questioned.

PMID- 10893810
TI  - Reader's interpretation questioned.

PMID- 10893811
TI  - Cover up those covers.

PMID- 10893812
TI  - Surgical emphysema and pneumomediastinum complicating dental extraction.
AB  - Subcutaneous and mediastinal emphysema is a rare complication of dental
      extraction and the use of air turbines has often been implicated. We describe a
      case which highlights a serious complication of the use of an air rotor for the
      removal of a right second mandibular molar.

PMID- 10893813
TI  - A single visit, multidisciplinary approach to the management of traumatic tooth
      crown fracture.
AB  - An immediate restorative technique resolving the acute problem of traumatic tooth
      fracture with pulpal and periodontal involvement, in which the fragment(s) are re
      alignable. Repositioning facilitated by a custom stent, using dentine/enamel
      bonding. A challenging, conservative and economically viable procedure within the
      compass of a single visit.

PMID- 10893814
TI  - Registration: stage II--intermaxillary relations.

PMID- 10893815
TI  - An investigation of patient management methods used for orthodontic extractions
      by general dental practitioners in north west England.
AB  - OBJECTIVE: To quantify the patient management methods used by dental
      practitioners for orthodontic extractions and to determine what factors influence
      their choice of method. DESIGN: Practitioners working in the General Dental
      Service in the area of the former North West Regional Health Authority were
      randomly sampled and sent a postal questionnaire. SETTING: General Dental Service
      in the North West of England. SUBJECTS: 204 completed questionnaires were
      returned; a response rate of 71.1%. INTERVENTIONS: Practitioners were asked about
      the patient management methods that they used for orthodontic extractions and
      what factors were important in choosing to use a general anaesthetic. OUTCOME
      MEASURES: The mean percentages of patients treated with local anaesthetic alone,
      general anaesthesia and inhalation sedation with local anaesthesia were
      calculated for the sample. Factors influencing the choice of method used were
      scored by the practitioners on a ten point scale. RESULTS: Local anaesthesia
      alone was used for two thirds of orthodontic extraction patients and general
      anaesthesia for one third. Inhalation sedation was rarely used. Poor patient
      cooperation and a nervous patient were the most important factors in choosing a
      general anaesthetic. CONCLUSIONS: Local anaesthesia is used for the majority of
      orthodontic extractions. However there remains an overuse of general anaesthesia
      and an underuse of inhalation sedation.

PMID- 10893816
TI  - Environmental monitoring of nitrous oxide during dental anaesthesia.
AB  - AIM: The study was carried out to see if levels of nitrous oxide in dental
      theatres and community dental clinics were being controlled in accordance with
      the Control of Substances Hazardous to Health Regulations. SETTING: A multi
      centre study looked at exposure levels in a dental teaching hospital and two
      community dental clinics in the South Wales area between 1997 and 1998. METHODS:
      A MIRAN infra-red spectrophotometer was used to measure static levels of nitrous
      oxide during general anaesthesia and conscious sedation. NIOSH method 6600 was
      used to collect personal samples of the individual administering the anaesthetic.
      RESULTS: The results showed compliance with the regulations when averaged out
      over an 8 hour time weighted average. However, over short periods of time peak
      concentrations of up to 1190 ppm were observed through static sampling, and up to
      734 ppm through personal sampling. CONCLUSIONS: The results highlighted the need
      to provide adequate control measures such as anaesthetic gas scavenging, to
      reduce occupational exposure to dental staff in dental operating theatres and
      community dental clinics, therefore providing a safe working environment.

PMID- 10893817
TI  - The chemical stain removal properties of 'whitening' toothpaste products: studies
      in vitro.
AB  - BACKGROUND: A considerable number of toothpastes are available as tooth whitening
      products. Most appear to contain ingredients that might remove extrinsic stains
      rather than change natural tooth colour. Extrinsic stain removal could be
      achieved by physical or chemical means. AIM: The purpose of this study was to
      measure the chemical stain removal properties of a range of whitening toothpaste
      products and experimental formulations using a standardised method in vitro.
      MATERIALS AND METHOD: 5 separate studies were conducted involving a total of 39
      agents of which 28 were whitening products, 7 were experimental formulations, 2
      were oxidising mouthrinses used as positive controls, 1 was a popular fluoride
      toothpaste product as a benchmark control, and 1 was water as the negative
      control. The formulations and controls varied in each study. The stain model was
      saliva/chlorhexidine/tea stain developed on optically clear acrylic to an optical
      density of at least 2.0. Groups of stained specimens were exposed to standard
      slurries or solutions of each test agent for 1 minute periods up to 5 minutes.
      Optical density readings were taken at each 1 minute time point. Analyses were
      based on per cent stain remaining after 5 minutes and time to 75% stain
      remaining. RESULTS: 3 toothpaste products achieved 100% stain removal by 5
      minutes; 2 of these in 3 out of 4 studies in which they were used. 4 experimental
      formulations also achieved 100% stain removal. In general agents with high total
      stain removal also had short times to 75% stain remaining. The majority of agents
      tested had low total chemical stain removal and prolonged times to 75% stain
      remaining. A few agents were little different from water and several similar in
      effect to the conventional fluoride toothpaste. This method in vitro tests agents
      under the best case scenario conditions for chemical stain removal. CONCLUSION:
      Only a small number of the whitening toothpaste products have good chemical stain
      removal potential; the majority are unlikely to achieve their claimed benefits
      through chemical stain removal. There is clearly a need for further data on the
      actual effects of such products using both methods in vitro and particularly in
      vivo or in situ.

PMID- 10893818
TI  - Letter from California--mandatory continuing education.
AB  - In Britain, mandatory continuing dental education is on its way. In California,
      we have had mandatory continuing dental education for some twenty-five years.
      Maybe it would help to see some of the good and bad sides of this, learn from
      some of our mistakes and see what does work and what does not work--at least in
      California.

PMID- 10893819
TI  - Ciguatera food poisoning linked to the consumption of imported barracuda-
      Montreal, Quebec, 1998.

PMID- 10893820
TI  - Imported dengue--Florida, 1997-1998.

PMID- 10893821
TI  - An outbreak of human blastomycosis: the epidemiology of blastomycosis in the
      Kenora catchment region of Ontario, Canada.

PMID- 10893823
TI  - An Advisory Committee Statement (ASC). National Advisory Committee on
      Immunization (NACI). Statement on adult/adolescent formulation of combined
      acellular pertussis, tetanus, and diphtheria vaccine.

PMID- 10893822
TI  - Respiratory virus surveillance. FluWatch project.

PMID- 10893824
TI  - Serious unexplained illness among drug injectors.

PMID- 10893825
TI  - Outbreaks of VTEC O157 infection linked to consumption of unpasteurized milk.

PMID- 10893826
TI  - Hepatitis C lookback exercise.

PMID- 10893827
TI  - Prions--new infectious agents.

PMID- 10893828
TI  - Type V chronic suppurative otitis media.

PMID- 10893829
TI  - Teflon granuloma.

PMID- 10893830
TI  - Maxillary sinoscopic view of polyps obstructing the natural ostium of the
      maxillary sinus.

PMID- 10893831
TI  - Electronystagmography in a patient with a peripheral vestibular disorder.

PMID- 10893832
TI  - Facial nerve neuroma appearing as a middle cranial fossa mass.

PMID- 10893833
TI  - Xanthoma of the temporal bone: a unique case of this rare condition.
AB  - Xanthoma of the temporal bone is extremely rare; we describe only the fourteenth
      reported case. Our case is further remarkable because it is the first report of
      such an occurrence in a patient with familial type III hyperlipoproteinemia.
      Moreover, while otalgia, infection, hearing loss, and tinnitus were the most
      common initial symptoms in the previous 13 cases, our patient reported only
      diplopia, vertigo, and unstable gait. The patient underwent a simple
      mastoidectomy and debulking, and his diplopia, vertigo, and unstable gait
      resolved.

PMID- 10893834
TI  - Otoacoustic emissions in patients with retrocochlear dysfunction: a report of
      five cases.
AB  - This article describes the results of otoacoustic emissions testing in five
      patients with sensorineural hearing loss. We conducted an audiologic evaluation
      and performed image and cerebral function studies on each patient. Our
      investigation revealed that all five had spontaneous otoacoustic emissions and/or
      distortion product otoacoustic emissions. Pharmacologic treatment with
      anxiolytics, antidepressants, and anticonvulsant drugs was successful in
      alleviating symptoms in three patients. An organic and a central functional cause
      of symptoms was found in the remaining two patients. Before pharmacologic
      therapy, the spontaneous otoacoustic emissions were of high intensity, and the
      distortion product emissions were minimal. Following drug therapy, the former
      disappeared and the latter appeared.

PMID- 10893835
TI  - Transmaxillary excision of a rare cavernous hemangioma of the infratemporal
      fossa.
AB  - Cavernous hemangiomas that manifest as a primary tumor of the infratemporal fossa
      are exceedingly rare. We report such a case in a 40-year-old woman. Her lesion
      was excised via a transantral anterior approach. Although this approach is
      usually recommended only for biopsy, in selected cases it can be used to excise a
      lesion without causing any significant complications. We recommend the
      transantral anterior approach for relatively small, benign lesions that show no
      evidence of invasion into surrounding tissues because it does not expose the
      patient to surgical complications such as transient or permanent facial nerve
      injury or cosmetic deformity.

PMID- 10893837
TI  - A case of barotrauma-induced pneumolabyrinth secondary to perilymphatic fistula.
AB  - We report the case of a 62-year-old woman who experienced pneumolabyrinth
      associated with a perilymphatic fistula. Her condition was diagnosed with the
      help of computed tomography, which detected the presence of an air bubble in the
      labyrinth, and middle ear exploration, which revealed that clear fluid was
      emanating from the round window niche in a manner consistent with the presence of
      a perilymphatic fistula. The niche was repaired with tragal perichondrium and
      bolstered with Gelfoam.

PMID- 10893836
TI  - Immobile vocal fold secondary to thyroid abscess: a case report.
AB  - Vocal fold paralysis as a result of a thyroid abscess is extremely rare. In this
      article, we report only the second documented case of such a finding. The
      paralysis was discovered after our patient, a 40-year-old woman, had come to the
      office with a complaint of discomfort in the right lower neck. Computed
      tomography confirmed the presence of an abscess in the posterior thyroid gland.
      Fine-needle aspiration did not identify any inflammatory or suspicious cells. The
      abscess was treated with hemithyroidectomy, and the paralysis resolved 3 weeks
      later. There has been no recurrence after 4 years.

PMID- 10893838
TI  - The role of radioactive iodine in salivary gland dysfunction.
AB  - The use of radioactive iodine has become an important adjunct to the treatment of
      thyroid cancer. Many normal tissues--including salivary glands, gastrointestinal
      mucosa, gonads, and lactating breast tissue--have the ability to concentrate
      radioactive iodine under normal circumstances. Although the mechanism is just
      beginning to be elucidated, it is this ability that might contribute to the
      immediate and long-term complications associated with radioactive iodine
      treatment. In some patients, the salivary complications can be permanent and
      might compromise daily functioning. In this article, we examine the salivary
      gland complications associated with radioactive iodine therapy, and we suggest
      potential protective mechanisms to circumvent these problems.

PMID- 10893839
TI  - The present and future of mental health care in Japan.

PMID- 10893840
TI  - Mental health services in China.

PMID- 10893841
TI  - Community resources for mental health care in India.

PMID- 10893842
TI  - Some perspectives on suicidal behaviour.
AB  - OBJECTIVE: To try and specify questions of special relevance for suicidological
      research. METHODS: Discussing the merits of questions pertaining to epidemiology
      and various theories on suicidal behaviour. RESULTS: Four types of questions are
      defined: How many persons show suicidal behaviour? Who are they? Why do they do
      it? and What can we do about it? Answers to the first three questions are
      required when approaching question four: What can we do about it? CONCLUSION: The
      complex patterns and backgrounds of suicidal behaviour call for
      interdisciplinarity and for an increase in both multifactorial and process
      related approaches as well as practicable, evidence-based and feasible
      intervention efforts.

PMID- 10893843
TI  - [Electroshock (ESK) and electroconvulsive therapy (ECT)].
AB  - OBJECTIVE: To discuss the ethical and legal basis of ECT use in Italy, one year
      after the regulation set up by the Minister of Health. METHOD: Literature review
      and presentation of authors' personal opinions. RESULTS: Despite being the oldest
      somatic therapy still practised in psychiatry, ECT effectiveness has been
      systematically evaluated only during the last 20 years, and its clinical
      indications have become progressively restricted. Yet there are wide variations
      between countries and within each individual country about the extension, the
      modalities and the indications for its use. ECT seems to be practised mainly in
      large scale public psychiatric hospitals and in private clinics, but its use in
      systems following a community approach is very limited. Wide variations exist
      also with reference to the severity of regulations imposed by governments or
      suggested by professional associations. The extent of education and auditing by
      university centres varies considerably, but is generally considered
      unsatisfactory. There are still some reports about possible political and
      repressive use of ECT in some countries, especially developing ones. CONCLUSIONS:
      The authors consider that every national system of care should have a clear
      policy and clear regulations about ECT. The provisions set up by the Italian
      Minister of Health seem to be consistent with Italian health policies and
      psychiatric community care.

PMID- 10893844
TI  - [Supply, demand and predictive factors of psychotherapies in 10 community mental
      health services in Emilia Romagna].
AB  - OBJECTIVE: The aim of the present paper is to assess the supply and demand of
      psychotherapy in mental health services and to identify the factors predicting
      the start of psychotherapy, using routine data, including 18 clinic and extra
      clinic variables, collected at 10 Mental Health Centers. SETTING: Ten Mental
      Health Services of Regione Emilia-Romagna. DESIGN: A prospective longitudinal
      study regarding all "new" users in 1995 followed for one year after the first
      visit. RESULTS: The percentage of the new users starting a psychotherapy was
      11.5%, corresponding to an overall one-year incidence of 5.6/10,000 inhabitants >
      or = 18 years old (range 0.9-14.8 across the 10 centres). The demand of
      psychotherapy in 1995 was 16.1%, including both the request of the patients and
      the primary care physicians (range 0.6-33%). The predictive factors for the
      beginning of the psychotherapy were: the presence of a psychologist at the first
      encounter, the request of the patient for a psychotherapy, age < 48 years, high
      educational level, being student, living with the family, the Mental Health
      Center; the broad diagnostic group of "neurotic" diagnoses resulted to have a
      twofold probability with respect to controls to start a psychotherapy. The
      logistic regression analysis of 18 variables couldn't find a predictive model
      with more than 33% sensitivity. CONCLUSIONS: The psychotherapeutic treatment is
      not predictable in the 10 Centers we studied, because of extreme differences in
      psychotherapy supply among Centers and probably because of uncertainty of
      therapeutic recommendations for psychotherapies.

PMID- 10893845
TI  - [Causes and psychosocial consequences of schizophrenia: the opinions of patient's
      relatives].
AB  - OBJECTIVE: Description of the opinions on schizophrenia and its psychosocial
      consequences in a sample of relatives of patients with schizophrenia, recruited
      in 30 Italian Mental Health Centres (MHC), stratified by geographic areas and
      population density. DESIGN: Cross-sectional study on key-relatives of clinically
      stable patients with a DSM-IV diagnosis of schizophrenia. Evaluation of
      relatives' opinions on schizophrenia and its psychosocial consequences, in
      relation to: a) patient's clinical and family's socio-demographic variables; b)
      geographic areas and population density. SETTING: 30 Italian MHC randomised and
      stratified by geographic areas (Northern, Central, Southern Italy) and population
      density (> 100,000 inhabitants; between 100,000 and 25,000 inhabitants; < 25,000
      inhabitants). Main outcome measures--Patient's clinical status and social
      functioning: Brief Psychiatric Rating Scale (BPRS) and Disability Assessment
      interview (AD). Interventions provided to patient and his/her family: Scheda di
      Rilevazione degli Interventi--Pattern of Care Schedule (SRI). Relatives' opinions
      on schizophrenia and its psychosocial consequences: Questionnaire on the Opinions
      of the Family (QOF). RESULTS: Data on 709 patients and their key-relatives were
      collected. Relatives' pessimistic opinions on social competence of patients with
      schizophrenia were found to be associated with: high levels of patient's
      disability, hostility and negative symptoms, relatives' knowledge of patient's
      diagnosis of schizophrenia, residence in a medium or low population density area,
      low levels of relative's education. Relatives' pessimistic opinions on social
      restrictions imposed by schizophrenia were found to be associated with high
      levels of disability and high number of hospital admissions in the patient and
      older age in the relative. CONCLUSIONS: The results of this study emphasise the
      need to: a) provide families with educational interventions covering not only
      clinical aspects of schizophrenia, but also those concerning disability and
      psychosocial consequences of the disorder; b) plan educational campaigns on
      mental illnesses which take into account the socio-cultural characteristics of
      the target populations.

PMID- 10893846
TI  - [Expressions of depression in Alzheimer's disease. The current scientific
      debate].
AB  - This overview analyses findings coming from researches that considered the
      interaction between depression and Alzheimer's disease (AD). METHOD: Information
      was collected from the Medline database and from a reasoned manual analysis of
      the published studies. RESULTS: The prevalence of depressive symptoms in patients
      with AD is elevated (40-50%). The role of depression in the pathogenesis of AD
      (independent, prodromal symptom, factor of risk) still must be defined. Data on
      family history of depression suggest that AD could act as stimulus triggering
      depression from a basis of a genetic vulnerability. From a biological point of
      view the onset of depression could derive from an unbalance between cholinergic
      and noradrenergic systems. Psychological understanding sees depression as a
      reaction of mourning for the cognitive deficit. Current diagnostic instruments
      validated on patients with AD constitute a good aid for the clinician and the
      researcher. The identification of depression coexisting with AD is difficult, in
      absence of clear affective symptoms, since the cognitive, psychomotor and
      vegetative symptoms belong both to depression and to AD. The affective disorders
      most frequently reported are major depression and dysthymia. The use of
      antidepressant drugs with the lowest anticholinergic profile is strongly
      recommended. Good results have been obtained also using various psychotherapeutic
      interventions adapted for dementia sufferers. CONCLUSIONS: The current scientific
      debate is based on information still limited and sparse. Future analyses should
      consider a better definition of the hypotheses related to psychopathology in AD,
      a standardised definition of cases and selection procedures and a prospective
      longitudinal design.

PMID- 10893847
TI  - [Prevalence and sensitivity of Candida albicans in cultures obtained at an
      oncologic hospital].
AB  - BACKGROUND: Prevalence Candida infections have increased and oncologic patients
      have risk factors for contacting them. They are associated with a long hospital
      stay and high mortality rate. Candida resistance to antifungal drugs has been
      reported. OBJECTIVES: To determine the prevalence of Candida grown in cultures
      from oncologic patients. To identify isolated species and to determine C albicans
      sensitivity to antifungal drugs. MATERIAL AND METHODS: During one year, different
      species of Candida spp. were isolated. They were inoculated in API-C-20 at 48 h.
      and cultivated in RPMI-1640. RESULTS: Cultures of 5,820 patients were collected,
      66.68% from outpatients and 33% from hospitalized patients. Candida spp grew in
      394 Candida albicans obtained from 81 cultures was the most frequent species
      (46.3%). One hundred were susceptible to Amphotericin B, 63% to Fluconazol, 59%
      to Ketoconazol and 31% to Itraconazol. Candidemia accounted for 24.6% of
      bloodstream infections. CONCLUSIONS: C. albicans had significant resistance to
      imidazoles and 100% were susceptible to Amphotericin B. Identification of species
      and susceptibility of Candida infections a useful tools because of the high
      proportion of Candida non-albicans species (53.7%). Candidemia accounted for
      5.076% of the infections.

PMID- 10893848
TI  - [Fasting glucose/insulin index and insulin levels 2-h after glucose load are
      predictors of the development of type 2 diabetes].
AB  - To determine whether fasting glucose/insulin (FG/I) ratio and insulin levels 2 h
      after 75-g oral load of glucose (IL-2 h PG) are predictors for type 2 diabetes
      mellitus, a comparative 2 year follow-up study was conducted. Ninety-six healthy
      subjects 30 years of age or older, randomly selected from the general population
      of Durango, Mexico were included in two groups: 1) risk group: members had both
      baseline FG/I ratio and IL 2-h PG within the lower and upper quartile,
      respectively, and 2) control group, whose members had baseline FG/I ratio and IL
      2-h PG within the second and third quartiles, respectively. Multivariate logistic
      regression was used to compute the relative risk for the development of type 2
      diabetes. The family history of diabetes (RR 10.1; IC95% 2.7-15.8, p < 0.01),
      glucose intolerance (RR 9.8; IC95% 1.7-13.4, p < 0.01), abdominal obesity (RR
      6.1; IC95% 1.5-10.1, p < 0.01), and the low FG/I ratio and high IL 2-h PG (RR
      3.3; IC95% 1.4-8.2, p < 0.05) were strong predictors for type 2 diabetes.
      Critical values for predicting criteria of FG/I ratio and IL 2-h PG were of 4.0 y
      180 microUI/ml, respectively. In conclusion, the measurement of FG/I ratio and IL
      2-h PG is an accurate indicator for estimating the risk of developing type 2
      diabetes.

PMID- 10893849
TI  - [Consistency and validity of the evaluation of the clinical chart].
AB  - OBJECTIVE: Assess the degree of external consistency and validity of the EXP CLIN
      instrument has for measuring the quality information contained in medical charts.
      MATERIAL AND METHODS: In a transverse comparative study, two hundred and twelve
      clinical charts were randomly selected belonging to patients seen at a pediatric
      hospital. The charts were assessed using the EXP-CLIN for phases: 1) internal
      assessment: by hospital personnel of the pediatric hospital, and, II) external
      assessment: by personnel from other hospitals. The results were analyzed using
      the concordance method. RESULTS: The concordance percentages were found to be 76%
      for medical charts and medical notes related with the process of diagnosis
      treatment, as well as the general characteristics of the clinical chart. The
      concordance percentages average was 88%, supporting the idea that when the EXP
      CLIN instrument is applied twice to the same chart, good concordance is obtained
      between the two measures. CONCLUSIONS: Given that the application of the
      instrument documented a good level of external consistency, its use is justified
      for assessing the quality of the information contained in the charts of the
      patients seen at our unit.

PMID- 10893850
TI  - [Accessibility of health services for users].
AB  - OBJECTIVE: To measure the accessibility to health services and determine a model
      to explain this accessibility. MATERIALS AND METHODS: All states of the Mexican
      Republic were included. The measurement of accessibility considers the
      availability of resources and the perception of barriers. Place of residence,
      education, participation in the work forces and household conditions were
      included in the model. RESULTS: The average of availability resources was 64.59%
      sd 15.68 (range 42 to 100) and the average corresponding to perception of
      barriers, 87.61% SD 4.04 (range 79.23 to 95.65). Accessibility was 71.50% SD
      10.74 (range 56 to 96). The states with highest accessibility were the Federal
      District and Baja California Sur and the lowest, Chiapas and Oaxaca. The model
      included education and labor participation (R2 = 0.67, p < 0.05). CONCLUSIONS:
      Accessibility was determined by socioeconomic factors.

PMID- 10893851
TI  - [Lymphoma. Current status and treatment].
AB  - The use of single-cell polymerize chain reaction analysis has allowed for a
      better understanding of the origin of Hodgkin's disease, Burkitt. The study of
      the mechanisms regulating apoptosis and the survival of neoplastic clones have
      opened a whole area of research. The Revised European-American List of lymphoid
      neoplasms must be presented in a form that facilitates the understanding,
      learning, and teaching of these disorders. There is a great need for a better
      definition of the new category of lymphoplasmacytic lymphoma, the variants of
      mantle cell lymphoma and marginal zone B-cell lymphomas, and the coming of age of
      the NK-cell lymphomas. Based on current data, it is difficult to determine the
      site of transplantation in the management of follicular, low-grade non-Hodgkin's
      lymphoma. These patients remain at risk of relapse after transplantation,
      mirroring results with conventional therapy. The treatment of aggressive
      lymphomas remains an area of significant controversy. The Intergroup Study
      concluded that none of the more recent regimens was superior to CHOP. Recent data
      suggest that high-dose therapy with consolidative autologous or allogenic
      transplant may benefit patients with aggressive histology lymphoma who have poor
      prognostic features.

PMID- 10893852
TI  - [Oxidative stress. Should it be measured in the diabetic patient?].
AB  - Oxidative stress has been defined as a loss of counterbalance between free
      radical or reactive oxygen species production and the antioxidant systems, with
      negative effects on carbohydrates, lipids, and proteins. It is also involved in
      the progression of different chronic diseases and apoptosis. Diabetes mellitus is
      associated to a high oxidative stress level through different biochemical
      pathways, i.e. protein glycosylation, glucose auto-oxidation, and the polyol
      pathway, mainly induced by hyperglycemia. Oxidative stress could also be involved
      in the pathogenesis of atherosclerotic lesions and other chronic diabetic
      complications. Measurement of oxidative stress could be useful to investigate its
      role in the initiation and development processes of chronic diabetic
      complications and also to evaluate preventive actions, including antioxidative
      therapy. Different attempts have been made to obtain a practical, accurate,
      specific, and sensitive method to evaluate oxidative stress in clinical practice.
      However, this ideal method is not currently available to date and the usefulness
      of the current methods needs to be confirmed in daily practice. We suggest
      quantifying oxidated and reduced glutation (GSSG/GSH) and the thiobarbituric
      reactive substances (TBARS) with currently alternatives. Currently available
      alternative methods while we await better options.

PMID- 10893853
TI  - [38-year-old woman with progressive severe headache].

PMID- 10893854
TI  - [Hypertrophic myocardiopathy with mid-ventricular obstruction and apical
      aneurysm. Report of a case and review of the literature].

PMID- 10893855
TI  - [External progressive ophthalmoplegia secondary to mitochondrial myopathy. Report
      of a case and review of the literature].
AB  - Progressive limitation of occular motility, accompanied by ptosis but usually
      without diplopia, occurs in many pathologic states, including mitochondrial
      diseases. A case with chronic progressive external ophthalmoplegia with onset
      during childhood, associated with proximal myopathy and dysphasia is presented.
      The muscle biopsy showed a myopathic pattern and abnormal subsarcolemmal
      mitochondrial deposits. Muscle biopsy for important in the correct diagnosis of
      this entity.

PMID- 10893856
TI  - [Marginal notes on tobacco in medicine and history].
AB  - Some characteristics of the tobacco plant and its use by native peoples of the
      Caribbean islands and New Spain are described. The importance of the tobacco
      habit in Newspanish and Europe regions, that became one of the main revenues of
      the respective governments, is emphasized. The incipient preoccupations
      concerning medical and social aid for the workers in tobacco factories are also
      exposed. The first aspect is reflected in an entire chapter of Ramazzini's
      treatise, which was the basis of the medicine of work, published in 1700. The
      second aspect is manifested in the creation, in 1796, of nursery schools for the
      children of working women in the tobacco factories of New Spain. Impressions of
      European travelers who visited New Spain and Independent Mexico are reported
      also. In opposition to the predictions of some visitors during the last century,
      with the passage of time, the tobacco habit instead of decreasing, became
      progressively more accentuated in all social classes. As a conditional
      aggravation, in the present day the noxious effects of tobacco smoke are combined
      with those of environmental contamination.

PMID- 10893857
TI  - [Flies and Parkinson disease].

PMID- 10893858
TI  - [Survey on the practice of autopsy at hospital units in the country].

PMID- 10893859
TI  - [Clinical medicine: between science and art].

PMID- 10893860
TI  - [Criteria on the legalization of abortion].
AB  - We revised ethical concepts related to abortion from the points of view of the
      mothers; life, health, and considerations are made concerning the embryo or fetus
      as a biological, ontological, moral, and potential person. Certain religious
      matters on abortion are described and commented on. Effects of abortion
      penalization in Mexico and the legislation in the Mexican states are examined, as
      well as the motives of depenalization in certain countries.

PMID- 10893861
TI  - [A scientifically proven miracle?].

PMID- 10893862
TI  - Analysis of the circadian clock gene period in the sheep blow fly Lucilia
      cuprina.
AB  - We have isolated a homologue of the period (per) gene from the Australian sheep
      blow fly, Lucilia cuprina, as part of a comparative approach to the analysis of
      dipteran circadian systems. Sequence analysis of the 4 kb per cDNA revealed the
      conservation of three functional domains, namely the PAS dimerization motif, and
      the nuclear and cytoplasmic localization domains. A fourth domain, the threonine
      glycine (TG) repeat region, is also conserved in L. cuprina per but has been
      severely truncated. No length variation was found in the TG repeat of L. cuprina
      or L. sericata collected from several different latitudinal zones. Expression
      analysis indicated a diel oscillation in per mRNA in LD 12:12 with a period of 24
      h and a peak at Zt 12. PER-immunoreactive protein oscillations were also
      demonstrated, with peak immunoreactivity lagging approximately 3 h behind peak
      mRNA levels. These results show the existence of a Drosophila-like circadian
      system in a calliphorid fly. They also provide evidence for the conservation of
      per function across the Diptera, and confirm the relevance of the Drosophila
      system as a model for fly circadian rhythms.

PMID- 10893863
TI  - Single nucleotide primer extension (SNuPE) analysis of the G6PD gene in somatic
      cells and oocytes of a kangaroo (Macropus robustus).
AB  - cDNA sequence analysis of the X-linked glucose-6-phosphate dehydrogenase (G6PD)
      gene has shown a base difference between two subspecies of the kangaroo, Macropus
      robustus robustus (wallaroo) and M. r. erubescens (euro). A thymine residue in
      the wallaroo at position 358 in exon 5 has been replaced by a cytosine residue in
      the euro, which accounts for the previously reported electrophoretic difference
      between the two subspecies. This base difference allowed use of the Single
      Nucleotide Primer Extension (SNuPE) technique to study allele-specific expression
      of G6PD at the transcriptional level. We began by examining G6PD expression in
      somatic cells and observed complete paternal X inactivation in all somatic
      tissues of adult female heterozygotes, whereas we found partial paternal allele
      activity in cultured fibroblasts, thus confirming previous allozyme
      electrophoresis studies. In late dictyate oocytes from an adult heterozygote, the
      assay also detected expression of both the maternal and paternal alleles at the
      G6PD locus, with the maternal allele showing preferential expression. Thus
      reactivation of the inactive paternally derived X chromosome occurs during
      oogenesis in M. robustus, although the exact timing of reactivation remains to be
      determined.

PMID- 10893864
TI  - Rates of movement of transposable elements on the second chromosome of Drosophila
      melanogaster.
AB  - The rates of movement of 11 families of transposable elements of Drosophila
      melanogaster were studied by means of in situ hybridization of probes to polytene
      chromosomes of larvae from a long-term mutation accumulation experiment.
      Replicate mutation-accumulation lines carrying second chromosomes derived from a
      single common ancestral chromosome were maintained by backcrosses of single males
      heterozygous for a balancer chromosome and a wild-type chromosome, and were
      scored after 116 generations. Twenty-seven transpositions and 1 excision were
      detected using homozygous viable and fertile second chromosomes, for a total of
      235,056 potential sources of transposition events and a potential 252,880
      excision events. The overall transposition rate per element per generation was
      1.15 x 10(-4) and the excision rate was 3.95 x 10(-6). The single excision (of a
      roo element) was due to recombination between the element's long terminal
      repeats. A survey of the five most active elements among nine homozygous lethal
      lines revealed no significant difference in the estimates of transposition and
      excision rates from those from viable lines. The excess of transposition over
      excision events is in agreement with the results of other in situ hybridization
      experiments, and supports the conclusion that replicative increase in
      transposable element copy number is opposed by selection. These conclusions are
      compared with those from other studies, and with the conclusions from population
      surveys of element frequencies.

PMID- 10893866
TI  - Measuring fitness by means of balancer chromosomes.
AB  - We present the theoretical background to a new method for measuring genetic
      variation for total fitness in Drosophila. The method allows heterozygous effects
      on total fitness of whole wild-type chromosomes to be measured under normal
      demography with overlapping generations. The wild-type chromosomes are competed
      against two balancer chromosomes (B1, B2, say), providing a standard genotype
      B1/B2 against which variation in the fitness effects of the wild-type chromosomes
      can be assessed. Fitness can be assessed in two ways: (i) at equilibrium of all
      three chromosomes under heterozygote advantage, and (ii) during displacement of
      one balancer by the other. Equilibrium with all three chromosomes present will be
      achieved only if the wild-type homozygote is not too fit, and if the fitnesses of
      the three heterozygotes are not too unequal. These conditions were not satisfied
      for any of a sample of 12 lethal-bearing chromosomes isolated from a random-bred
      laboratory population of Drosophila. At equilibrium, genotypic frequencies show
      low sensitivity to changes in genotypic fitness. Furthermore, where all four
      genotypes are viable and fertile, supplementary information from cages with only
      two chromosomes present and from direct measurements of pre-adult viability are
      required to estimate fitnesses from frequencies. The invasion method has the
      advantages of a greater sensitivity and of not requiring further data to estimate
      fitnesses if the wild-type homozygote is fertile. However, it requires that
      multiple samples be taken as the invasion progresses. In a discrete generation
      model, generation time influences fitness estimates from this method and is
      difficult to estimate accurately from the data. A full age-structured model can
      also be applied to the data from both types of experiment. For the invasion
      method, this gives fitness estimates close to those from the discrete generation
      model.

PMID- 10893865
TI  - Do malaria parasites mate non-randomly in the mosquito midgut?
AB  - Polymerase chain reaction (PCR)-based genotyping of oocysts dissected from
      mosquito midguts has previously been used to investigate overall levels of
      inbreeding within malaria parasite populations. We present a re-analysis of the
      population structure of Plasmodium falciparum malaria using diploid genotypes at
      three antigen-encoding loci in 118 oocysts dissected from 34 mosquitoes. We use
      these data to ask whether mating is occurring at random within the mosquito
      midgut, as is generally assumed. We observe a highly significant deficit of
      heterozygous oocysts within mosquitoes at all three loci, suggesting that fusion
      of gametes occurs non-randomly in the mosquito gut. A variety of biological
      explanations, such as interrupted feeding of mosquitoes, positive assortative
      mating and outcrossing depression, could account for this observation. However,
      an alternative artefactual explanation--the presence of non-amplifying or null
      alleles--can account for the observed data equally well, without the need to
      invoke non-random mating. To evaluate this explanation further, we estimate the
      frequencies of null alleles within the oocyst population using maximum
      likelihood, by making the assumption that non-amplifying oocysts at any of the
      three loci are homozygous for null alleles. Observed levels of visible
      heterozygotes fit closely with those expected under random mating when non
      amplifying oocysts are accounted for. Other lines of evidence also support the
      artefactual explanation. Overall inbreeding coefficients have been recalculated
      in the light of this analysis, and may be considerably lower than those estimated
      previously. In conclusion, we suggest that the deficit of heterozygotes observed
      is unlikely to indicate non-random mating within the mosquito gut and is better
      explained by misscoring of heterozygotes as homozygotes.

PMID- 10893867
TI  - Genetic variability in milking speed of dairy goats.
AB  - The present investigation deals with the genetic variability of milking speed,
      measured as the volume of milk collected during the first minute of milking
      (MD1), and its association with dairy traits. Data originated from 2589
      lactations of 1421 Alpine goats, sired by 93 bucks, measured between 1985 and
      1997 at the Moissac Goat Experimental Station (Lozere, France). Two genetic
      analyses were carried out. Firstly, a polygenic model was used to estimate
      genetic and phenotypic parameters among milking speed and dairy traits using a
      multiple-trait animal model. Secondly, segregation analysis was used to test the
      hypothesis of mixed model inheritance (polygenes + major gene) for MF1.
      Heritability and repeatability of MF1 under the polygenic model were high (0.65
      and 0.82, respectively). Estimated genetic and phenotypic correlations between
      milking speed and dairy traits were low, positive for yields and negative for
      contents. Segregation analysis yielded a highly significant likelihood ratio,
      confirming the segregation of a major gene with two alleles with partial
      dominance. The difference between the mean values of the two homozygotes was
      around 2.3 phenotypic standard deviation units of the trait. The major gene
      explained more than 60% of the estimated total genetic variance. The estimate of
      the 'residual' heritability, after taking into account the effect of the major
      locus, was 0.30.

PMID- 10893868
TI  - The influence of environmentally induced heterogeneity on age-specific genetic
      variance for mortality rates.
AB  - Using parametric models that describe the increase in mortality rates with age,
      we demonstrate that environmentally induced heterogeneity among genetically
      identical individuals is sufficient to generate biased estimates of age-specific
      genetic variance. Although the magnitude of the bias may change with age, one
      general trend emerges: the true genetic variance at the oldest ages is likely to
      be dramatically underestimated. Our results are robust to different
      manifestations of heterogeneity and suggest that such a bias is a general feature
      of these models. We note that age-dependent estimates of genetic variance for
      characters that are correlated with mortality (either genetically or
      environmentally) can be expected to be similarly affected. The results are
      independent of sample size and suggest that the bias may be more widespread in
      the literature than is currently appreciated. Our results are discussed with
      reference to existing data on mortality variance in Drosophila melanogaster.

PMID- 10893869
TI  - Interrelations between effective population size and other pedigree tools for the
      management of conserved populations.
AB  - Genetic parameters widely used to monitor genetic variation in conservation
      programmes, such as effective number of founders, founder genome equivalents and
      effective population size, are interrelated in terms of coancestries and
      variances of contributions from ancestors to descendants. A new parameter, the
      effective number of non-founders, is introduced to describe the relation between
      effective number of founders and founder genome equivalents. Practical
      recommendations for the maintenance of genetic variation in small captive
      populations are discussed. To maintain genetic diversity, minimum coancestry
      among individuals should be sought. This minimizes the variances of contributions
      from ancestors to descendants in all previous generations. The method of choice
      of parents and the system of mating should be independent of each other because a
      clear-cut recommendation cannot be given on the latter.

PMID- 10893870
TI  - A general mixture model approach for mapping quantitative trait loci from diverse
      cross designs involving multiple inbred lines.
AB  - Most current statistical methods developed for mapping quantitative trait loci
      (QTL) based on inbred line designs apply to crosses from two inbred lines.
      Analysis of QTL in these crosses is restricted by the parental genetic
      differences between lines. Crosses from multiple inbred lines or multiple
      families are common in plant and animal breeding programmes, and can be used to
      increase the efficiency of a QTL mapping study. A general statistical method
      using mixture model procedures and the EM algorithm is developed for mapping QTL
      from various cross designs of multiple inbred lines. The general procedure
      features three cross design matrices, W, that define the contribution of parental
      lines to a particular cross and a genetic design matrix, D, that specifies the
      genetic model used in multiple line crosses. By appropriately specifying W
      matrices, the statistical method can be applied to various cross designs, such as
      diallel, factorial, cyclic, parallel or arbitrary-pattern cross designs with two
      or multiple parental lines. Also, with appropriate specification for the D
      matrix, the method can be used to analyse different kinds of cross populations,
      such as F2 backcross, four-way cross and mixed crosses (e.g. combining backcross
      and F2). Simulation studies were conducted to explore the properties of the
      method, and confirmed its applicability to diverse experimental designs.

PMID- 10893871
TI  - Efficient marker-based recurrent selection for multiple quantitative trait loci.
AB  - We studied the efficiency of recurrent selection based solely on marker genotypes
      (marker-based selection), in order to increase favourable allele frequency at 50
      previously detected quantitative trait loci (QTLs). Two selection procedures were
      investigated, using computer simulations: (1) Truncation Selection (MTS), in
      which individuals are ranked based on marker score, and best individuals are
      selected for recombination; and (2) QTL Complementation Selection (QCS), in which
      individuals are selected such that their QTL composition complements those
      individuals already selected. Provided QTL locations are accurate, marker-based
      selection with a population size of 200 was very effective in rapidly increasing
      frequencies of favourable QTL alleles. QCS methods were more effective than MTS
      for improving the mean frequency and fixation of favourable QTL alleles. Marker
      based selection was not very sensitive to a reduction in population size, and
      appears valuable to optimize the use of molecular markers in recurrent selection
      programmes.

PMID- 10893872
TI  - [Subjective health and rehabilitation needs of LVA insured patients currently
      applying for medical rehabilitation].
AB  - Unlike services paid through the Federal German Health Insurance, applications
      for medical rehabilitation are granted based on defined criteria. In some cases,
      rehabilitation is granted without apparent reason. Seeking to minimize this
      problem, this study integrates information on the subjective health status into
      the decision-making process of medical examiners. The return rate of the postal
      questionnaire (87%) as well as the evaluation of the examiners documented the
      practicability of the approach. The interviewed applicants described themselves
      as more limited in their abilities on several health dimensions (ICIDH) compared
      to a population of prestationary interviewed rehabilitation patients, whereby the
      standard deviations in both populations were similar. Furthermore, the applicants
      rarely utilized complementary treatments and sociomedical/legal advice. A
      surprising result lies in the mostly non-existent association between the
      subjective health status and the medical decisions. This constitutes a
      significant difficulty in legitimizing the decision-making process of the medical
      examiners.

PMID- 10893873
TI  - [Management and care of severely ill patients in ambulatory care nursing--results
      of an evaluation study].
AB  - The last few years have seen numerous attempts to expand outpatient nursing and
      adapt it to the changing health problems of the population. Even so, outpatient
      nursing care for severely ill patients and those with complex nursing needs still
      has its shortcomings. Today, it may well be the case that these patients, too,
      are being discharged far more quickly from the inpatient into the outpatient
      sector thanks to ever greater constraints on hospital care, but there they are
      running up against a wide variety of problems, ones that first became obvious
      with AIDS but can also be seen with other groups of patients suffering from
      serious illnesses. The paper goes into the question of what the care of severely
      ill patients and those requiring nursing attention looks like in the outpatient
      sector, what difficulties arise from the point of view of the nursing services
      involved, and what challenges will have to be met in the future to improve their
      situation.

PMID- 10893874
TI  - [Risk factors for urothelial carcinoma: drinking measures, smoking and other life
      style-related risk factors--results of the Berlin Urothelial Study (BUS)].
AB  - With the exception of smoking and several occupational exposures there is little
      knowledge about risk factors for urothelial cancer. A case control study in the
      area of former West Berlin was performed from 1990-1995 to investigate the role
      of several lifestyle risk factors, such as smoking, drinking behaviour and
      regular intake of analgesics and laxatives. The study includes 647 hospital-based
      incident cases with bladder cancer (n = 571), renal pelvis cancer (n = 51), and
      ureter cancer (n = 25), and 647 population-based controls which were matched
      individually by sex and age. Data analyses were carried out using standard
      methods for case control studies (conditional multiple logistic regression
      analysis). Odds ratios (OR) and 95% confidence intervals (CI) were applied as
      effect parameter. Statistically significantly increased odds ratios were observed
      for current smoking (OR: 3.46, 95% CI: 2.50-4.78), previous but now abandoned
      smoking (OR: 1.51, 95% CI: 1.09-2.81), and for regular intake of laxatives (OR:
      2.52, 95% CI: 1.56-4.09). Furthermore, an increased risk for urothelial cancer
      was observed for daily consumption of three and more litres of cold drinks (OR:
      2.65 95% CI: 1.12-6.24). The results underline that lifestyle factors other than
      smoking may contribute to a higher risk of urothelial cancer.

PMID- 10893875
TI  - [Health behavior of smokers--results of the TACOS (Transitions in Alcohol
      Consumption and Smoking) Study].
AB  - The German TACOS Project (Transitions in Alcohol Consumption and Smoking)
      provided an opportunity to examine the patterns of health behaviours (nutrition,
      physical activity, alcohol consumption) of current smokers, ex-smokers and non
      smokers with special regard to different degrees of severity of nicotine
      dependence. Data were collected in the adult general population of Lubeck and 46
      surrounding communities, resulting in a representative sample of 4075
      individuals. In this sample, 37.3% were current smokers, 22.5% were ex-smokers,
      25.0% of smokers were severely nicotine-dependent. As in other empirical
      investigations, current smokers had an unhealthy lifestyle in general. Smokers
      compared to ex-smokers and non-smokers consumed unhealthy foods more frequently,
      reported less physical activity and were more likely to consume hazardous levels
      of alcohol. Special attention was paid to comparing different degrees of severity
      of nicotine dependence. A high degree of nicotine dependence was associated with
      poor health behaviours. Data show that smoking, unhealthy nutrition, lack of
      physical activity, and hazardous levels of alcohol consumption occur in
      combination and that unhealthy behaviour patterns vary according to the severity
      of nicotine dependence. The presence of multiple unhealthy behaviours requires
      special secondary preventive interventions for smokers. The association of these
      combined health hazards must be controlled in determining the independent health
      risk due to one of these factors.

PMID- 10893876
TI  - [Tobacco prevention in apprentices--evaluation of a general practice project "not
      smoking is cool!"].
AB  - PURPOSE: In recent years the incidence of adolescent smokers has increased
      steeply. Taking this into account, current anti-smoker campaigns should be
      reconsidered. Great importance must be attached to the apprentice group, since
      adolescents in professional training have frequently not been reached
      sufficiently by the preventive efforts. This study presents a tobacco prevention
      campaign among adolescents which was conducted in a large Swiss industrial
      company in 1998. METHODS AND SAMPLE: A total of 430 apprentices took part in the
      prevention campaign which intentionally targeted adolescent behaviour. Of these,
      40 apprentices were trained as mediators for tobacco prevention in advance. On
      the prevention day, the mediators communicated their know-how and experiences to
      their working groups. To evaluate the campaign, the apprentices were surveyed via
      standardised questionnaires on their smoking habits before the prevention
      campaign began. One month after the prevention day they were surveyed again on
      their current smoking habits and how the campaign had affected them. RESULTS: The
      study showed that apprentices smoke heavily despite high awareness of the
      negative consequences. Some 30% of the trainees admitted smoking regularly.
      Another 11% said they were occasional tobacco consumers. No significant gender
      difference was noticeable. Especially striking was that the adolescents often
      justified their own smoking as habit and dependence on tobacco. The prevention
      campaign was well received by the adolescents. It set about half of the smokers
      thinking over their smoking habits. No change in smoking habits, however, could
      be demonstrated one month after the campaign. CONCLUSIONS: Prevention among
      adolescents beyond the mandatory school period is a special challenge, since one
      cannot take advantage of the school's network. Within the scope of the campaign
      described here, it was possible to reach 430 apprentices of a major company. The
      study shows a great need for on-target smoking prevention in this sector. In the
      future, studies should examine whether tobacco prevention campaigns for
      apprentices should already contain secondary prevention elements from the outset.
      They should also assess if the effects could be further improved by introducing
      structural and other ongoing health-promotion measures.

PMID- 10893877
TI  - [Computer-assisted instruction in medicine: a multicenter evaluation study in 7
      German language media resource centers].
AB  - EVA, a multicentre study of seven computer resource centres (CRCs) in three
      German-speaking nations, was carried out over a period of six months to gather
      structural and process data regarding the use of computer-based instruction (CBI)
      applications in medicine, and to identify the factors contributing to a more
      successful integration of CBI into the medical curriculum. 618 machine-readable
      questionnaires from CRC users and seven questionnaires on structural data of the
      participating CRCs covering 51 computer stations were evaluated. For Macintosh
      workstations (n = 34), an additional digital log-protocol was analysed. In
      conclusion, it seems that so far less than 10% of medical students use CBI
      programs in German-speaking countries. The data show the presently still poor
      integration of CBI into the medical curriculum.

PMID- 10893878
TI  - [Guidelines and recommendations for insuring good epidemiological practice (GEP).
      German Professional Society of Epidemiology].

PMID- 10893879
TI  - [Aspirin: a return to the source rather than a big disappointment].

PMID- 10893880
TI  - [From hormones to the psyche, a chief conductor of emotions and behavior].

PMID- 10893881
TI  - [Prophylactic and therapeutic vaccine therapy in papillomavirus infections].
AB  - HPV types are carcinogenic in cervical cancer. This view is supported by
      epidemiological and biological evidence. Knowledges of HPV gene expression, of
      natural history of cervical HPV infection and neoplasia and of tumoral antigenic
      expression have lead to develop two strategies for vaccine development: 1
      Prophylactic vaccines of HPV infections. 2-Therapeutic vaccines aimed to control
      the tumor growth and even to cure the patient. After an update of natural history
      of cervical HPV infection, the different target of vaccine strategies. The first
      published trials will be presented.

PMID- 10893882
TI  - [Bladder endometriosis. Apropos of 4 cases and review of the literature].
AB  - The aim of our study is to evaluate the diagnostic and therapeutic attitude
      toward endometriosis of the bladder. We have analysed four observations treated
      in the gynecologic service of Hotel-Dieu in Paris between January 1989 and
      January 1998, which represents 1.3% of all endometriosis operated during this
      period. Every patient underwent echography, RMN, UIV and cystoscopy. In all for
      cases a surgical treatment by laparotomy was realised. The choice of this way is
      explained by the multiple localisations of endometriosis in three cases and the
      impossibility of a coelioscopic treatment in the forth. The anatomopathologic
      exam found endometriosis in all of the cases.

PMID- 10893883
TI  - [Genetic prediction in medicine].
AB  - Presymptomatic or predictive genetic testing concerns healthy people. Its aim is
      to determine individuals at risk for a disease. Presymptomatic testing concerns
      mainly Mendelian diseases; an abnormal test result will lead to development of
      the disease in most cases in later life. Predictive testing concerns
      multifactorial or low penetrating Mendelian diseases; the test result will modify
      the risk of disorder occurring but with a much smaller degree of certainty.

PMID- 10893884
TI  - [Isolated and recurrent hydrothorax during ovarian stimulation].
AB  - Acute, insulated hydrothorax can be observed after ovulation induction without
      other signs of hyperstimulation. Usually, it is unilateral, localized on the
      right side and associated with ongoing pregnancy. We regularly noted a good
      outcome although the pathogenesis of this affection is still enigmatic. It may
      recur in the case of a new ovarian stimulation.

PMID- 10893885
TI  - [Phytoestrogens in the contraindication of hormone replacement therapy. The
      problem of breast cancer].

PMID- 10893886
TI  - [Lipid evaluation in the follow up of menopausal women under hormone replacement
      therapy].

PMID- 10893887
TI  - [The initial entry point in gynecologic laparoscopic surgery].

PMID- 10893888
TI  - [Intrauterine device and infertility: have the risks changed? Can an intrauterine
      device be used in a nulliparous woman?].

PMID- 10893889
TI  - ACE inhibitors in high risk cardiovascular patients: a new hope from the HOPE
      study.

PMID- 10893890
TI  - Atrial fibrillation: epidemiology, mechanisms and management.
AB  - The incidence of AF, the most common sustained arrhythmia in clinical practice,
      increases with age and coronary artery disease, hypertension and valvular heart
      disease are common underlying substrates; however, occasionally, AF may occur
      without any underlying heart disease. The most widely accepted theory of its
      mechanism is Moe's multiple wavelet hypothesis, although recent studies are
      helping to shed light on other mechanisms, including the focal origin of AF in
      some patients. Most patients experience palpitations, but fatigue, dyspnoea, and
      dizziness may also occur. Therapy includes prevention of thromboembolism, control
      of rate, and restoration and maintenance of sinus rhythm. The risks and benefits
      of each treatment modality need to be assessed according to each patient's
      circumstances. Unlike other arrhythmias, there is still no highly successful
      therapy for treating AF. However, significant advances are being made using non
      pharmacological approaches to either prevent or cure this troublesome arrhythmia.

PMID- 10893891
TI  - Apolipoprotein(a) polymorphism and its association with plasma lipoprotein(a)
      levels: a north Indian study.
AB  - Elevated levels of lipoprotein(a) has been regarded as an independent risk factor
      for coronary, peripheral and cerebral atherosclerosis. The enormous intra
      personal variation in the plasma concentration of lipoprotein(a) is almost
      entirely controlled by the apolipoprotein(a) i.e. gene locus on the chromosome 6q
      26-27. The apolipoprotein(a) molecule is highly polymorphic and is known to exist
      in multiple, genetically determined isoforms. These polymorphisms may be
      responsible for difference in promoter activity, variable size of
      apolipoprotein(a) and thereby variation in plasma lipoprotein(a) concentration.
      We studied the effect of two types of polymorphisms, (i) variation in length of
      the pentanucleotide repeat in the 5' flanking region starting -1373 bp upstream
      of AUG codon, and (ii) the Kringle-4 type 2 size polymorphism, on plasma
      lipoprotein(a) levels in North Indian population. The study group consisted of 88
      angiographically assessed male coronary artery disease patients (age range 30-70
      years) and 83 age- and sex-matched healthy controls. The pentanucleotide repeat
      polymorphism was analysed using polymerase chain reaction. In all, 8/11
      pentanucleotide repeat isoforms were observed. Using SDS-agarose gel
      electrophoresis and immunoblotting isoforms having 12-50 Kringle-4 type 2 repeats
      were detected. Our study indicates a strong association of elevated plasma
      lipoprotein(a) concentration with coronary artery disease. An inverse correlation
      was seen between lipoprotein concentration and isoform size for both the
      pentanucleotide repeat polymorphism and the Kringle-4 type 2 polymorphisms;
      statistically significant difference (p = 0.001) was, however, observed only for
      the later.

PMID- 10893892
TI  - Apolipoprotein(a) polymorphism and plasma lipoprotein(a) levels.

PMID- 10893893
TI  - A study of lipid levels in uncomplicated hypertension.
AB  - A number of risk factors for coronary artery disease are known to be present in
      hypertensive patients, the most important being hyperlipidemia. An analysis of
      the lipid profiles of 3,182 uncomplicated non-diabetic patients (2,425 males, 757
      females) who attended two institutions of Patna city between 1992-1998 was
      conducted alongwith 4,131 controls. Mean total cholesterol was slightly higher
      (but statistically significant; p < or = 0.05) in hypertensives (191.8 mg/dL vs
      190.1 mg/dL) as compared to the control group; mean total cholesterol-HDL ratio
      was also higher (4.65 vs 4.48) in hypertensives (p < or = 0.05). As per National
      Cholesterol Education Programme guidelines, 1,069 (33.6%) patients had
      cholesterol level above 200 mg/dL while 850 (26.7%) had triglycerides over 200
      mg/dL among the hypertensive group. An abnormal total cholesterol-HDL ratio (>
      4.5) was found in 1,600 (50.3%) of the hypertensives; this was by far the most
      common abnormality. With increasing severity of hypertension, the prevalence of
      elevated total cholesterol, LDL cholesterol and low HDL cholesterol was higher;
      triglyceride levels were less affected. These results indicate that an abnormal
      total cholesterol-HDL ratio is the most common variety of dyslipidemia in
      uncomplicated hypertension.

PMID- 10893894
TI  - Saccular coronary aneurysms: angiographic and clinical profile and follow-up of
      22 cases.
AB  - Saccular coronary aneurysms are defined as aneurysms with the transverse
      dimension at least 1.5 times the longitudinal dimension. Out of 3,200 coronary
      angiograms reviewed, there were 22 patients (20 males) with saccular coronary
      aneurysms (totalling 25 aneurysms). The morphology of the aneurysms, the extent
      and severity of associated coronary lesions, the clinical profile and follow-up
      data of these patients were analysed. Aneurysms were located in left main
      coronary artery 3 (12%), left anterior descending coronary artery 13 (52%), right
      coronary artery 5 (20%) and left circumflex 4 (16%). There were 5 large aneurysms
      (> 15 mm in diameter) (1 in left main coronary artery, 2 each in right coronary
      artery and left anterior descending coronary artery) averaging 32 mm in size.
      Fifteen aneurysms had significant coronary artery stenosis located proximal to
      it, supporting the theory of post-stenotic dilatation as the aetiology of
      aneurysm formation. Two patients had associated muscle bridges distal to the
      aneurysm; 20 had atherosclerotic coronary artery disease and one had coronary
      artery ectasia. Five patients were lost to follow-up, which ranged from 1 year to
      19 years (mean 5.3 +/- 4.1 years). No patient had history suggestive of rupture
      of the aneurysm on follow-up. Two patients had myocardial infarction in the
      territory of the vessel with the aneurysm. Rest of the patients were in NYHA
      class I/II. One large right coronary artery aneurysm was subjected to
      aneurysmectomy due to symptoms of tricuspid valve obstruction. One left main
      coronary artery aneurysm measuring 12 mm, on follow-up of 19 years increased in
      size to 45 mm, in addition the patient developed a right coronary artery
      aneurysm. Coronary risk factor profiles in the 20 patients with atherosclerotic
      coronary artery disease and aneurysms were similar to age- and sex-matched
      control population with atherosclerotic coronary artery disease without
      aneurysms.

PMID- 10893895
TI  - Megadose heparin and streptokinase produce similar TIMI 3 flow at discharge in
      patients of acute myocardial infarction presenting between 7-12 hours.
AB  - The present study was undertaken to assess the impact of megadose heparin bolus
      on angiographic patency of infarct-related artery in patients of acute myocardial
      infarction presenting between 7-12 hours and to compare it with streptokinase.
      Forty-seven patients (27 males, mean age 58.1 +/- 9.6 years) of acute myocardial
      infarction between 7-12 hours of onset of chest pain were randomised to receive
      either megadose heparin bolus (300 IU/kg body weight, group 1, n = 24; or
      streptokinase 1.5 million units over one hour, group 2, n = 23). Parameters noted
      were: relief of pain at 90 minutes, 50 percent or more resolution of ST segment
      at 90 minutes, TIMI grade flow and left ventricular ejection fraction at
      discharge. Mean age (59.0 +/- 12.9 years in group 1; 57.2 +/- 8.1 years in group
      2), mean time to drug (7.5 +/- 1.3 hours in group 1; 7.8 +/- 1.6 hours in group
      2), site of anterior wall infarction (12 in group 1, 10 in group 2), relief of
      pain at 90 minutes (15 in group 1, 14 in group 2) and more than 50 percent
      resolution of ST segment elevation at 90 minutes (12 patients in each group) were
      similar. On coronary angiography performed in 42 patients (21 in each group) at a
      mean interval of 7.2 +/- 1.3 days after acute myocardial infarction, TIMI grade 3
      flow was seen in 7 (33.3%) patients in each group and TIMI grade 2/3 flow was
      also similar in both the groups (p = NS). No major bleed occurred in either
      group. We conclude that heparin given as a megadose bolus produces similar TIMI 3
      flow in infarct-related artery as compared to streptokinase in acute myocardial
      infarction patients presenting between 7-12 hours.

PMID- 10893896
TI  - Heart rate variability in dilated cardiomyopathy.
AB  - Chronic heart failure is associated with excessive neurohormonal activation.
      Analysis of heart rate variability is considered a valid technique for assessment
      of the autonomic balance of the heart. Twenty symptomatic patients of dilated
      cardiomyopathy in NYHA class II-IV symptomatic status and as many normal controls
      were subjected to 24 hours Holter monitoring to assess the heart rate variability
      with both time domain and frequency domain analysis. Age of the patients ranged
      from 12 to 67 years (mean +/- SD 38.6 +/- 7 years), the male-female ratio was
      4:1. The left ventricular ejection fraction of the patients was between 18-42
      percent (mean +/- SD 30.2 +/- 9%) and all received diuretics, digoxin and
      angiotensin-converting enzyme inhibitors. Heart rate variability parameters
      measured included mean heart rate with standard deviation, hourly heart rate with
      SD and the mean of all normal RR intervals from the 24-hour recording. Time
      domain measures calculated were SD of all normal RR intervals, SD of 5 minute
      mean RR intervals and root mean square of difference of successive RR intervals.
      Using spectral plots, frequency domain subsets of low frequency and high
      frequency were analysed and expressed in normalised units. Total power was also
      measured. In the dilated cardiomyopathy patients, mean 24-hour heart rate in
      beats per minute was significantly higher in comparison to controls (82 +/- 13 vs
      72 +/- 8; p < 0.001) whereas mean hourly heart rate with standard deviation
      (msec) was significantly lower (97 +/- 41 vs 232 +/- 25; p < 0.001), SD of all
      normal RR intervals (msec) was 85.5 +/- 26.3 vs 139.4 +/- 16.9 in controls (p <
      0.001), SD of 5 minute mean RR intervals (msec) was also significantly less in
      patients in comparison to controls (75.8 +/- 39.6 vs 130.8 +/- 20.3; p < 0.001).
      However, although root mean square of difference of successive RR intervals
      (msec) was reduced in patients (30.1 +/- 9.3 vs 37.3 +/- 11.7; p < 0.05), the
      difference was non-significant. Low frequency power (0.05-0.15 Hz) (normalised
      units) was reduced in the dilated cardiomyopathy group (0.0721 +/- 0.003 vs 0.136
      +/- 0.047 in the control group; p < 0.001). High frequency power (0.35-0.50 Hz)
      (normalised units) (0.08 +/- 0.05 in patients vs 0.09 +/- 0.02 in controls; p >
      0.1) and total power frequency (0.02-0.50 Hz) (normalised units) (0.34 +/- 0.05
      in patients vs 0.35 +/- 0.12 in controls; p > 0.1) was non-significantly
      different in the two groups. Regression analysis showed a significant decrease in
      SD of all normal RR intervals, SD of 5 minute mean RR intervals, low frequency,
      high frequency, total power and a non-significant decrease in root mean square of
      difference of successive RR intervals with a decrease in ejection fraction
      percent whereas there was a significant decrease in SD of all normal RR
      intervals, SD of 5 minute mean RR intervals, low frequency and total power and a
      less significant decrease in root mean square of difference of successive RR
      intervals and high frequency power with an increase in NYHA class. At 6 months
      duration, 6 patients were lost to follow-up, 3 patients were readmitted (2 for
      congestive cardiac failure, one of paroxysmal supraventricular tachycardia). One
      patient who was NYHA class IV at baseline was readmitted for congestive cardiac
      failure and showed much lower heart rate variability parameters compared to the
      average of the patients. We conclude that in symptomatic dilated cardiomyopathy
      patients, heart rate variability parameters are significantly reduced in
      comparison to control subjects.

PMID- 10893897
TI  - Surgical considerations of univentricular heart with total anomalous pulmonary
      venous connection.
AB  - Out of the 600 patients undergoing univentricular repair during the last 11
      years, 20 children had associated total anomalous pulmonary venous connection.
      The objective was to outline the clues to establish the diagnosis of this rare
      disease combination and the various surgical options available to manage the
      same. Bidirectional Glenn, bilateral bidirectional Glenn, total cavopulmonary
      connection and atriopulmonary connection were performed in combination with
      rechannelling of various types of total anomalous pulmonary venous connection in
      20 children aged 6 months to 36 months (mean +/- SD 17.65 +/- 9.02 months).
      Diagnosis could be established pre-operatively in only 13 (65%) patients. Out of
      6 early deaths (30%), 4 were directly attributable to missed diagnosis. No late
      deaths occurred over a follow-up period ranging from 1 month to 132 months. None
      of the surviving children required reoperation and all are in NYHA functional
      class I. Doppler echocardiography of the surviving children revealed unrestricted
      atrio/cavopulmonary anastomosis and pulmonary vein to atrium connection in all
      survivors. Our own experience, coupled with a review of the literature, indicates
      that a missed diagnosis increases the hospital mortality. Cross sectional 2D
      echocardiography is a superior method of detection of associated total anomalous
      pulmonary venous connection compared to angiocardiography. Exclusion of the
      diagnosis of anomalous pulmonary venous connection is imperative in all
      univentricular hearts pre-operatively and on operation table. Failure to
      recognise this disease combination results in formation of a closed systemic
      circuit after bidirectional Glenn or a modified Fontan of connection and is
      lethal as happened in our early experience. It is suggested that one-stage Fontan
      operation should be performed only if other criteria for Fontan procedure are
      satisfied.

PMID- 10893898
TI  - Successful ablation of idiopathic right ventricular inflow tachycardia.

PMID- 10893900
TI  - Bacterial endocarditis caused by Brucella melitensis biotype I.

PMID- 10893899
TI  - Coronary arterial fistula from both the coronaries to pulmonary artery in
      association with congenital bicuspid aortic stenosis.

PMID- 10893901
TI  - Renal artery in-stent restenosis: treatment with high speed rotational
      atherectomy.

PMID- 10893902
TI  - Primary chylopericardium--a case report.

PMID- 10893903
TI  - Haemopericardium with cardiac tamponade and pleural effusion in chronic myeloid
      leukemia.

PMID- 10893904
TI  - Retained intracardiac foreign body following attempted percutaneous transluminal
      mitral commissurotomy.

PMID- 10893905
TI  - Mycotic aneurysm of the left pulmonary artery in tetralogy of Fallot: single
      stage surgical correction.

PMID- 10893906
TI  - Successful treatment of type I and type III primary endoleaks and a femoral
      pseudoaneurysm using Passager stent grafts following endoluminal repair of an
      abdominal aortic aneurysm.

PMID- 10893907
TI  - Risk factors for coronary artery disease in Indians: emerging trends.

PMID- 10893908
TI  - Signal transduction during cardiac hypertrophy: new insights.

PMID- 10893909
TI  - Standards and concepts in valve surgery. Report of the task force: European Heart
      Institute (EHI) of the European Academy of Sciences and Arts and the
      International Society of Cardiothoracic Surgeons (ISCTS).

PMID- 10893910
TI  - Prevention validation and accounting platform: a framework for establishing
      accountability and performance measures of substance abuse prevention programs.
AB  - The field of substance abuse prevention has neither an overarching conceptual
      framework nor a set of shared terminologies for establishing the accountability
      and performance outcome measures of substance abuse prevention services rendered.
      Hence, there is a wide gap between what we currently have as data on one hand and
      information that are required to meet the performance goals and accountability
      measures set by the Government Performance and Results Act of 1993 on the other.
      The task before us is: How can we establish the accountability and performance
      measures of substance abuse prevention programs and transform the field of
      prevention into prevention science? The intent of this volume is to serve that
      purpose and accelerate the processes of this transformation by identifying the
      requisite components of the transformation (i.e., theory, methodology, convention
      on terms, and data) and by introducing an open forum called, Prevention
      Validation and Accounting (PREVA) Platform. The entire PREVA Platform (for short,
      the Platform) is designed as an analytic framework, which is formulated by a
      collectivity of common concepts, terminologies, accounting units, protocols for
      counting the units, data elements, and operationalizations of various constructs,
      and other summary measures intended to bring about an efficient and effective
      measurement of process input, program capacity, process output, performance
      outcome, and societal impact of substance abuse prevention programs. The
      measurement units and summary data elements are designed to be measured across
      time and across jurisdictions, i.e., from local to regional to state to national
      levels. In the Platform, the process input is captured by two dimensions of time
      and capital. Time is conceptualized in terms of service delivery time and time
      spent for research and development. Capital is measured by the monies expended
      for the delivery of program activities during a fiscal or reporting period.
      Program capacity is captured by fourteen measurement units, tapping into the
      dimensions of staff resources and community assets. Staff resources are, in turn,
      operationalized in terms of staff size, staff certification status, staff
      turnover rate, and the accreditation status of a provider agency. Community
      assets are operationalized by the number of community centers accessible to the
      funded agency, number of formalized teams or antidrug coalitions active in the
      catchment area, and other social/human services providers with whom the
      prevention agency has formalized networks. The totality of process output from
      all sources of program activities is reduced to eighteen classes of measures.
      These are operationalized by thirty-three summary measures. Some of these
      include: total count of events facilitated; total number of clients served;
      average number of clients served per event; clients served by single and multiple
      program sessions; classification of target population in terms of the severity of
      risk as defined by the Institute of Medicine; age groups and race/ethnicity of
      clients served; number of program participants retained by recurring programs;
      number of clients who have completed the program; penetration rates to the target
      population; client attrition rates; average referral rates per provider per time
      interval; referral success rates; and so on. All process output measures
      specified in the Platform are derived from two broad classes of events classified
      as either products or services. The collectivity of these measures is expected to
      present a cost-effective, parsimonious, yet comprehensive picture of the entire
      spectrum of the process output, i.e., "what came out of the program as program
      activities". For the measurement of performance outcomes, two types of data are
      incorporated into the Platform: outcome data from individuals and the behavior
      (or performance) of social indicators from aggregated data bases. Individual data
      are used to evaluate the outcome of substance abuse programs

PMID- 10893911
TI  - Leishmaniasis.

PMID- 10893912
TI  - Radiographic scoring method for the assessment of the severity of nutritional
      rickets.
AB  - Radiographic changes of rickets are well characterized, but no method of grading
      the severity of these changes has been in general use. Consequently, it is
      difficult to compare objectively or follow radiographic improvement. We
      prospectively evaluated the utility and reproducibility of a scoring method for
      measuring the severity of rickets. A 10-point score for radiographs of wrists and
      knees was devised to assess the degree of metaphyseal fraying and cupping and the
      proportion of the growth plate affected. The score progresses in half point
      increments from zero (normal) to 10 points (severe). Four trained physicians
      independently scored radiographs on two separate occasions from 67 children with
      active rickets. A broad representation of mean radiographic scores was moderately
      correlated with alkaline phosphatase (r = 0.58). Interobserver correlation of
      radiographic scores was 0.84 or greater for all observer pairs and intraobserver
      correlation was 0.89 or greater for each observer. Researchers and clinicians
      should find the score useful to assess objectively the severity of rickets.

PMID- 10893913
TI  - A new method for maturity determination in newborn infants.
AB  - A two-part study was conducted in several centres in Nigeria to develop and
      evaluate a simple method for maturity determination in newborn infants. The first
      part involved the development of a six-feature model which included head
      circumference, mid-arm circumference, skin texture, ear form, breast size and
      genitalia. These were features which had highly significant correlation with
      gestational age in the studied population. The model consisted of a chart showing
      the regression line of gestational age on total maturity score based on the six
      selected features. It had comparable accuracy with the Dubowitz method. Different
      subgroups of term and low-birth weight infants were also reliably identified by
      the model. In the evaluation of sick newborn infants, the model was more accurate
      than a previously reported abbreviated method from the same population. The model
      is suggested as an appropriate clinical tool for rapid and reliable maturity
      determination in healthy and sick newborn infants.

PMID- 10893914
TI  - Ocular manifestations in children with HIV infection in Dar es Salaam, Tanzania.
AB  - A study of ocular lesions among 62 HIV seropositive and 47 HIV seronegative
      children admitted to the paediatric ward of Muhimbili Medical Centre was
      conducted. The prevalence of ocular manifestations was 38 per cent among the HIV
      seropositive children and 25 per cent among HIV seronegative children. While
      conjunctival lesions were common in both groups, fundus and corneal lesions were
      more common in HIV seropositive children. The common lesions were macular oedema,
      haemorrhages and sheathing of retinal vessels. In addition, HIV seropositive
      children had a 10 per cent prevalence of abnormal visual acuity compared with HIV
      seronegative children who had a 6 per cent prevalence. This study showed that
      ocular manifestations of HIV is high in African children and can be confounded by
      nutritional status. The commonest non-ocular manifestation was pulmonary
      tuberculosis and malnutrition. Children with HIV infection should have an ocular
      examination.

PMID- 10893915
TI  - Clinical support can make the difference in exclusive breastfeeding success among
      working women.
AB  - Exclusive breastfeeding has generally been considered incompatible with working
      separated from the infant. This prospective, controlled intervention trial shows
      that breastfeeding support, including anticipatory counseling and monthly
      clinical follow-up of the mother and infant, can significantly increase the
      percentage of infants exclusively fed with breastmilk at the end of 6 months of
      life. Over 80 per cent of women from control and intervention groups expressed a
      desire to breastfeed for more than 6 months and more than 50 per cent thought it
      was best for the infant to be exclusively breastfed for 6 months. Only 6 per cent
      of women in the control group were able to complete 6 months of exclusive
      breastmilk feeding compared to 53 per cent of those in the intervention group.
      The most important difference between the strategies used by both groups of
      mothers for maintaining exclusive breastmilk feeding after returning to work was
      that only 23 per cent of the control group practiced milk expression compared to
      66 per cent in the intervention group. All women from the supported group stated
      that they would advise a friend to combine exclusive breastfeeding and work and
      that they would like to do so again with another child.

PMID- 10893916
TI  - Incidence, clinical spectrum, and outcome of intrauterine infections in neonates.
AB  - A prospective study was undertaken on the incidence of intrauterine infections by
      screening 1302 cord blood samples for total IgM by radial immunodiffusion.
      Specific IgM against cytomegalovirus (CMV), rubella and Toxoplasma were estimated
      in cord blood samples found to contain total IgM > 20 mg/dl. All these neonates
      were examined at birth and at discharge. Cord blood samples with total IgM > 20
      mg/dl were further screened for specific IgM against rubella, CMV and Toxoplasma.
      Neonates found to have positive specific IgM were followed-up for hearing,
      opthalmological and developmental assessment. Raised cord blood (IgM > 20 mg/dl)
      was found in 270/1302 (20.6 per cent). Mean birth weight was comparable in babies
      with raised (> 20 mg/dl) or low (< 20 mg/dl) cord blood total IgM. Incidence of
      prematurity and low birth weight were not statistically different in babies with
      raised cord blood IgM when compared to those with low cord blood IgM levels.
      Similarly, incidence of intrauterine growth retardation (IUGR) idiopathic was
      similar in two groups. Specific IgM for rubella was found to be positive in eight
      (0.6 per cent). Of these, three had symptomatic rubella infection. Two mothers of
      these symptomatic babies had exanthematous viral illness during first trimester.
      Specific IgM for CMV was found to be positive in 23 (1.8 per cent) while two
      infants had symptomatic CMV disease. None of the babies was found to have
      specific IgM against Toxoplasma. One baby with symptomatic CMV disease and one
      with rubella died. Another baby with symptomatic CMV disease developed neonatal
      hepatitis which improved on follow-up but the infant went on to develop
      sensorineural deafness. All other asymptomatic babies with specific IgM positive
      against rubella and CMV were found to have normal vision, hearing and development
      on follow-up.

PMID- 10893917
TI  - Concentration of eight trace minerals in milk and sera of mother-infant pairs in
      northern Nigeria.
AB  - Breastmilk from 15 healthy lactating women (21-31 years of age) from the hot,
      semi-arid sahel of Africa were analysed for copper, iron, zinc, magnesium,
      manganese, sodium, potassium, and phosphorus. Relative to published data from
      other populations worldwide, the milk of the Jos women appeared to contain
      adequate levels of magnesium, manganese, sodium, potassium, phosphorus and iron,
      but relatively low concentrations of zinc (1.07 micrograms/ml) and copper (170
      micrograms/l). The sera of the exclusively breastfed infants nursed by these
      mothers contained levels of all these minerals that are within the international
      reference range of values. No statistically significant correlation was observed
      between the level of a particular mineral in the mothers' milk and the sera of
      their nursing infants.

PMID- 10893918
TI  - Serum concentration of retinol, beta-carotene, cholesterol, and triglycerides in
      Saudi school children.
AB  - Vitamin A and beta-carotene are often considered as members of a family of
      antioxidant vitamins that can show protective effects against oxidative stress
      and some chronic diseases. Data on vitamin A and beta-carotene status in Saudi
      children are sparse. In the current study the serum concentrations of retinol,
      beta-carotene, cholesterol and triglycerides were determined in 500 healthy Saudi
      children aged 6 to more than 18 years. The study group consisted of 247 (49.4 per
      cent) females and 253 (50.6 per cent) males, living in the Riyadh area of Saudi
      Arabia. The serum retinol levels in all age groups were within the range reported
      from industrial countries and in all age groups the mean values were higher than
      the critical level of 0.2 microgram/ml. No significant difference in serum
      retinol levels was observed between male and female subjects (p > 0.05), but age
      was found to be an important covariant of the vitamin. The mean serum beta
      carotene concentration in all age groups was significantly higher than previously
      reported which may suggest an improvement in Saudi children's diets, notably in
      respect to fruit and vegetable intake. Females seemed to retain a higher level of
      beta-carotene compared to males which confirmed earlier reports of a positive
      correlation between age and the beta-carotene level in females. Only males in the
      age group 6-8.9 years old had a significantly higher level of beta-carotene than
      their female counterparts; 11.95 +/- 5.85 micrograms/ml compared to 8.53 +/- 3.5
      micrograms/ml (p < 0.05).

PMID- 10893919
TI  - Intestinal nematodes, Toxocara infection, and pyogenic liver abscess in children:
      a possible association.
AB  - Eosinophilia and intestinal helminths are frequent in children with pyogenic
      liver abscess (PLA) diagnosed in Vitoria (Brazil). For these reasons we
      hypothesized that nematode infection with larvae migrating through the tissues
      (Ascaris, Strongyloides, Ancylostoma, Necator and Toxocara) may be a predisposing
      factor for PLA in children. We compared the prevalence of intestinal helminth and
      Toxocara infection between children with PLA and a control group of children with
      no evidence of PLA at the Children's Hospital N.S. da Gloria in Vitoria. From
      October 1996 to February 1998, 13 children with PLA and 110 children with
      diseases other than PLA provided five stool samples (Hoffman, Baerman and Kato
      Katz methods) and one blood sample for anti-Toxocara antibodies (ELISA IgG, with
      previous adsorption with Ascaris suum antigen). All PLA and comparison children
      belonged to a low socioeconomic class and lived in similar conditions. The
      frequency of intestinal nematodes and anti-Toxocara antibodies were significantly
      higher in PLA patients than in controls (intestinal helminths: 10/13 or 76.9 per
      cent in PLA cases and 31/110 or 28.1 per cent in controls; OR = 8.94; 95 per cent
      confidence interval (CI): 1.97 < OR < 50.06; anti-Toxocara antibodies: 9/13 or
      69.2 per cent in PLA and 31/110 or 28.1 per cent in controls; OR = 6.59; 95 per
      cent CI: 1.65 < OR < 31.05). Moreover, the degree of eosinophilia was higher in
      PLA patients. Malnutrition was present in both groups. Hemoglobin was 9.5 g/dl in
      PLA patients and 9.7 g/dl in controls; p = 0.900. Serum levels of IgA and IgM
      were normal or above normal, with no difference between the two groups, but the
      levels of IgG and IgE were higher in PLA patients. Although there is some missing
      data in respect to some socioeconomic parameters in affected and comparison
      groups. these results support the hypothesis that helminth infection with larvae
      migrating through tissues may be a predisposing factor for PLA in children. Th2
      cell activation and downregulation of Th1 cells, induced by helminths, thus
      reducing the microbicidal activity of phagocytes, as well as the granulomatous
      reaction around the larvae (mainly of Toxocara sp.) causing the trapping of
      bacteria in liver, may be possible explanations for the increased risk for PLA in
      children with intestinal nematodes and/or Toxocara infection.

PMID- 10893920
TI  - Predictors of failure of nasal continuous positive airway pressure in treatment
      of preterm infants with respiratory distress syndrome.
AB  - A case-control study was carried out on 97 consecutive preterm (< 37 weeks)
      infants to determine predictors associated with failure of nasal continuous
      positive airway pressure (CPAP) in the treatment of respiratory distress syndrome
      (RDS). Logistic regression analysis showed that only three risk factors were
      significantly associated with failed CPAP. These were: moderate or severe RDS
      (odds ratio: 5.9; 95 per cent confidence interval (CI): 2.2-16.0); septicemia
      during CPAP therapy (OR: 8.8; 95 per cent: CI 1.5-50.7); and pneumothorax during
      CPAP therapy (odds ratio: 6.9; 95 per cent: CI 1.1-41.7).

PMID- 10893922
TI  - Chelation therapy and cardiac status in young patients with thalassemia major.

PMID- 10893921
TI  - Adenosine deaminase activity and lysozyme levels in children with tuberculosis.
AB  - Serum adenosine deaminase (ADA) activity and lysozyme levels were measured in 51
      patients with tuberculosis (21 pulmonary, 15 miliary, 11 neurotuberculoma and
      four abdominal plus osteoarticular) and 20 healthy controls. The mean serum ADA
      activity and lysozyme levels were significantly raised in children with different
      forms of tuberculosis in comparison with controls (p < 0.001). The
      neurotuberculoma cases had the lowest mean enzyme levels and the differences were
      significant when compared with other forms of tuberculosis. The cut-off serum ADA
      activity of > or = 42 IU/l and lysozyme level of > or = 20 U/l were diagnostic of
      tuberculosis with 100 per cent sensitivity. A significant correlation was
      observed between the two parameters (r = 0.66; p < 0.001). Thus, with compatible
      clinical presentation, the raised serum level of either ADA or lysozyme can be
      used as a supportive diagnostic test.

PMID- 10893923
TI  - Gall bladder wall edema in serology proven pediatric dengue hemorrhagic fever: a
      useful diagnostic finding which may help in prognostication.

PMID- 10893925
TI  - A survey on breastfeeding using the IMCI approach in a neonatal unit in Tanzania.

PMID- 10893924
TI  - The sickle cell gene frequency in southern Iran.

PMID- 10893927
TI  - The academic--corporate interface in medicine.

PMID- 10893926
TI  - Causes of death in a rural area of South Africa: an international perspective.
AB  - The study compares the cause of death profile in a rural area of South Africa
      (Agincourt), with that in a rural area of West Africa (Niakhar), and in a
      developed country with the same life expectancy (France, 1951) in order to
      determine causes with high and low mortality and priorities for future health
      interventions. In the two African sites, causes of death were assessed by verbal
      autopsies, whereas they were derived from regular cause of death registration in
      France. Age-standardized death rates were used to compare cause-specific
      mortality in the three studies. Life expectancy in Agincourt was estimated at 66
      years, similar to that of France in 1951, and much higher than that of Niakhar.
      Causes of death with outstandingly high mortality in Agincourt were violent
      deaths (homicide and suicide), accidents (road traffic accidents and household
      accidents), certain infectious diseases (HIV/AIDS, tuberculosis, diarrhea and
      dysentery), certain chronic diseases (cancer of genital organs, liver cirrhosis,
      gastrointestinal hemorrhage, maternal mortality, epilepsy, acute rheumatic fever,
      and pneumoconiosis) and malnutrition of young children (kwashiorkor). Causes of
      death with lower mortality than expected were primarily respiratory diseases
      (pneumonia, bronchitis, influenza, lung cancer), other cancers, vaccine
      preventable diseases (measles, whooping cough, tetanus), and marasmus. Verbal
      autopsies could be used in a rural area of a developing country without formal
      cause of death registration to identify the most salient health problems of the
      population, and could be compared with a formal cause of death registration
      system of a developed country.

PMID- 10893928
TI  - Sports and drugs in primary care.

PMID- 10893929
TI  - Concussion and head injury.

PMID- 10893930
TI  - Common athletic knee injuries.

PMID- 10893931
TI  - The female athletic triad.

PMID- 10893932
TI  - Scoliosis due to a hemivertebra.

PMID- 10893933
TI  - Multiple gestation births in Rhode Island, 1989-1998.

PMID- 10893934
TI  - Public health genetics in Rhode Island: first steps.

PMID- 10893935
TI  - Medical records requests: doctors, stop violating the law!

PMID- 10893936
TI  - Joining together to combat poverty: everybody welcome and needed.

PMID- 10893937
TI  - Nuclear weapons for ever? The NPT review conference--and after.

PMID- 10893938
TI  - Globalization and health--some issues.
AB  - Globalization is happening. But it appears that it has been associated with a
      rise in inequalities both between and within nations. Financial and trade
      liberalization, the main motors of the current phase of globalization, have been
      introduced with reckless abandon and little thought to the consequences. Future
      policy advice must bolster the role of the state in defending populations from
      the excesses of market forces, and there should be rigorous analysis of the
      health and other social impacts of economic policies.

PMID- 10893939
TI  - The World Trade Organization: implications for health policy.
AB  - Agreements negotiated at the World Trade Organization already have important
      implications for health and health policy. They impact on the ability of
      governments to regulate trade in the interests of health; on national and
      international governance and public health standards; and on the future of the
      precautionary principle. Agreements on trade-related aspects of intellectual
      property rights and trade in health services could benefit the multi-national
      health care and pharmaceutical industries, and impact negatively on cost and
      equity.

PMID- 10893940
TI  - Food and its safety.
AB  - The manner in which food is produced, distributed, sold and controlled has
      changed radically over the last fifty years. This has lead to dissociation and
      deskilling of consumers while control of quality and safety have remained in the
      hands of legislators and producers. With the globalization of trade consumers
      perceive in foods unacceptable levels of food safety risk. In the new century the
      conflict between perceived safety and manageable risk may be resolved by open
      debate and the establishment of mechanisms which include the ethical dimensions
      of food production and use.

PMID- 10893941
TI  - A needs assessment in a refugee mental health project in north-east London:
      extending the counselling model to community support.
AB  - In the United Kingdom, as elsewhere, mental health services are becoming
      increasingly aware that existing services may not meet the needs of different
      minority groups. This paper outlines the model used to set up a project focusing
      specifically on refugee mental health needs in Waltham Forest, in north-east
      London. Funding was available for one sole mental health worker and careful
      consideration was therefore given as to how her time should be used. A thorough
      needs assessment of refugees living in Waltham Forest determined that the
      provision of therapy or counselling alone would not be the most appropriate means
      of addressing refugees' needs. The intervention model developed therefore
      included awareness raising and community mobilization, in addition to one-to-one
      clinical sessions. The empowerment, training and support of refugee community
      groups became a central part of the work, which helped to establish and then
      consolidate links between mainstream services and individual refugees.

PMID- 10893942
TI  - Living with rattlesnakes: Chernobyl and Dounreay.
AB  - After the Three Mile Island nuclear plant accident in 1979, a local Pennsylvania
      resident told The New York Times 'You live with that plant over there for years
      and years and don't think much about it. But it's like living with a rattlesnake.
      Sooner or later it's going to bite you. You just don't know when.' As we enter
      the twenty-first century, many communities find themselves living with
      rattlesnakes--one at least of which has already bitten. This article considers
      the official responses to Chernobyl in the first decade after the accident and
      compares them to the statements surrounding the sudden 1998 decision to
      decommission the nuclear reprocessing plant at Dounreay in Scotland.

PMID- 10893943
TI  - Inter-group aggression: the multi-individual organism and the survival instinct.
AB  - Inter-group aggression, carried out at the level of the in-groups and out-groups
      of ethnocentric theory, continued unabated throughout the twentieth century. Its
      frequency, together with its ferocity, indicates a potent biological cause. We
      have evolved as social animals, and it is postulated that evolution has proceeded
      to such an extent that 'multi-individual social organisms', that is, 'social
      groups that fight each other are self-sustaining, self-replicating whole
      containing interdependent parts'. This results from the total integration of
      individuals into the social structure and culture of the in-group; individuals
      are inseparable from their society and evidence for this proposal is given.
      Cohesion is given through the collective consciousness and collective memory. The
      analogy is to multicellular organisms that evolved from the association of single
      cell organisms. All biological organisms are subject to the survival instinct,
      which is thus the potent biological cause of inter-group aggression. Groups
      compete for territory and see other groups as a threat. Prevention of inter-group
      aggression should come from the insight that threatening behaviour endangers the
      integrity of the society of out-groups, initiating conflict.

PMID- 10893944
TI  - International Week of Science and Peace (IWOSP).

PMID- 10893945
TI  - [Standards, trends and challenges in HIV medicine].

PMID- 10893946
TI  - [Less is more--what counts is the number of tablets. Looking at antiretroviral
      substances].

PMID- 10893947
TI  - [Administer a protease inhibitor immediately? Proceeding strategically in HIV
      therapy].

PMID- 10893948
TI  - [Holding option open for subsequent treatment. Beginning therapy with a protease
      inhibitor].

PMID- 10893949
TI  - [Living with HIV therapy. Side effects are the main problem].

PMID- 10893950
TI  - [HIV post-exposure prevention. Minutes are important--therefore PEP (postexposure
      prophylaxis) emergency set].

PMID- 10893951
TI  - [Preventing AIDS. Cool--the condom campaign].

PMID- 10893952
TI  - [A child despite HIV? Starting a family is not a taboo any more].

PMID- 10893953
TI  - [Need for review in research and practice. HIV infection in women is increasing].

PMID- 10893954
TI  - [Almost 6,000 double-infected patients in Germany. Hepatitis C burden in HIV
      patients].

PMID- 10893955
TI  - [Highly active antiretroviral therapy. A simple combination, but high
      effectiveness].

PMID- 10893956
TI  - [Safety in routine clinical practice. Hypersensitivity can be managed].

PMID- 10893957
TI  - [Discussed with a current case: physician confidentiality issue in conflict].

PMID- 10893958
TI  - [Controlled tapering of medication. What do structured treatment withdrawal
      achieve?].

PMID- 10893959
TI  - [Daily routine in an HIV specialty practice. Ambulatory patient monitoring.
      Interview by Waldtraut Paukstadt].

PMID- 10893960
TI  - [Choice of first-line therapy. It depends on long-term effectiveness].

PMID- 10893961
TI  - [Long-term success in routine clinical practice. Effectiveness trial passed].

PMID- 10893962
TI  - [HIV therapy from the viewpoint of the patient. Four out of five suffer with side
      effects].

PMID- 10893963
TI  - [New therapy approaches for HIV infected patients. Hope on the immune front].

PMID- 10893964
TI  - [Non-nucleoside reverse transcriptase inhibitors. First line therapy].

PMID- 10893965
TI  - [Effectiveness also in general practice conditions. Just as good in routine
      practice as in studies].

PMID- 10893966
TI  - [Looking at the HIV test. Qualitative virus detection a cost-effective
      alternative?].

PMID- 10893967
TI  - [New generation protease inhibitor. Tolerance and potency, a tight association].

PMID- 10893968
TI  - [Development of immunizing agents against dengue].
AB  - The four serotypes of dengue flaviviruses are transmitted mainly by the Aedes
      aegypti mosquito, and some epidemics have been attributed to Ae. albopictus, Ae.
      polynesiensis, and various species of the Ae. scutellaris complex. The risk
      factors involved in dengue mortality and morbidity are related to the human host
      (genetic characteristics of infected persons; lifestyles, immune status, and
      health conditions of people; basic sanitation of dwellings; and water supply) and
      to the virus (genetic variability between and among serotypes, different
      pathogenicities, and geographic distribution). Notwithstanding the lack of
      knowledge of the immunopathobiology of dengue fever, important advances have been
      made in terms of a protective immune response, using attenuated dengue viruses or
      antigens produced by means of recombinant technologies. Efforts have been made
      since the 1940s to develop dengue vaccines. Immunity acquired from natural
      infection is specific for each serotype, and as many as three different serotype
      infections have been reported in one individual. For this reason, a tetravalent
      vaccine may likely be needed. Candidate vaccines against the four serotypes have
      been tested in volunteers and have proven to be immunogenic and safe. Although
      attenuated live virus vaccines are promising, more study is needed regarding
      their effectiveness and safety. Currently, several studies are ongoing to develop
      dengue vaccines using antigens from structural proteins (particularly E
      glycoprotein) and nonstructural proteins, with recombinant DNA technology and
      other biomolecular technologies. With the same goal, various expression vectors
      are being used, including Escherichia coli, baculovirus, vaccinia virus, and
      yellow fever virus. Unfortunately, no satisfactory results have been obtained in
      humans. The need for effective dengue vaccines is great, given the serious
      worldwide problem of the transmission of the four serotypes. Effective
      immunization against dengue would contribute to its prevention, with a positive
      cost-benefit relationship. Endemic dengue affects young children, and they should
      be immunized through the Expanded Program on Immunization.

PMID- 10893969
TI  - Primary health care lessons from the northeast of Brazil: the Agentes de Saude
      Program.
AB  - Market-led economic reforms are usually viewed as being in conflict with
      government-stimulated socioeconomic development for disadvantaged groups.
      Nevertheless, Ceara, a poor state in the Northeast of Brazil, has since 1987
      pursued both of those strategies simultaneously. One part of that approach has
      been a program of nurse-directed auxiliary health workers serving about 5 million
      people--almost all the persons outside the capital city and half of those in the
      capital. The system requires that the auxiliaries, called agentes de saude, live
      in the local communities that they serve. The health agents visit each home once
      a month to carry out a small number of priority health activities. While health
      agent positions are in high demand, the minimum-wage salary that the agents
      receive makes up only a small portion of the state budget. A key aspect of the
      system is timely and comprehensive information, which is based on agent visits
      and is managed by trained nurses. Since the health agents system was launched,
      there has been a rapid decline in infant mortality, a rapid rise in immunization,
      identification of bottlenecks limiting the utilization of other medical
      resources, and timely interventions in times of crisis. The health agents system
      has combined administrative decentralization with financial centralization during
      a period of electoral democratization. The system has strengthened Ceara's
      commitment to primary care even as market-oriented changes have reduced the
      overall role of government. The Ceara program is being copied throughout the
      Northeast and other regions of Brazil. The key role that nurses play in the Ceara
      program in organizing and leading a system of basic primary care in poor
      neighborhoods and rural areas may provide useful lessons for other countries. In
      addition, Ceara does not have many of the favorable characteristics of other
      countries that have successfully invested in primary health care. Ceara thus
      represents a more achievable model for other countries, where, like Brazil,
      income, educational levels, and land tenure equity are limited.

PMID- 10893970
TI  - [Surveillance of infant deaths in local health systems: assessment of verbal
      autopsy reports and of information gathered from health agents].
AB  - Knowing the vital statistics of a population is fundamental in controlling
      morbidity and mortality and improving living conditions. In Brazil, however, the
      available health information systems do not provide reliable vital statistics.
      This study was carried out in Quixada, Icapui, and Jucas, three municipalities in
      the state of Ceara that had good coverage by primary health care services. The
      study used an epidemiological instrument known as a "verbal autopsy" and
      investigated 215 (90%) of the 237 deaths of children younger than 1 year
      identified in 1993 and 1994 in the three communities. We investigated
      socioeconomic characteristics; sanitary conditions; nutritional status; the
      course of illness, health care, and death; the cause of death; and the operation
      of the national mortality information system and of the community health agents
      system. According to the verbal autopsies, diarrhea was the cause of death in 39%
      of the cases, followed by premature birth (17%), and acute respiratory infections
      (10%). Even though 79% of the families had sought formal health care services
      during the child's illness, 49% of the infants had died at home. This suggests
      limited effectiveness in the identification and treatment of sick infants. In 84%
      of the cases the family sought help from folk healers. Although community health
      agents reported 78% of the deaths, only 29% of the families had sought help from
      the agents during the children's illnesses. In terms of the statistical agreement
      between the information on the cause of death provided by community health agents
      and by the verbal autopsies, the agreement was good for diarrhea, intermediate
      for other causes, and low for acute respiratory infections. Making verbal autopsy
      a routine part of primary health care services in Ceara would provide invaluable
      information for local health care teams and would raise a critical consciousness
      fostering a reduction in infant mortality.

PMID- 10893971
TI  - [Quality of drinking water and diarrheal diseases in Cuba, 1996-1997].
AB  - A study was conducted in 1996 and 1997 in 31 Cuban cities having a population
      greater than 35,000, in order to determine if there was a relationship between
      drinking water quality and the frequency of acute diarrheal diseases (ADD). We
      used the level of disinfection (based on chlorine concentration) as well as the
      level of bacterial contamination (based on the presence of coliform bacteria) as
      water quality indicators, and the frequency of ADD was calculated on the basis of
      the number of visits (per 100,000 inhabitants) to individual family physicians
      and to physicians on call in hospitals and polyclinics that were prompted by ADD.
      Weekly determinations of chlorine concentrations and monthly measurements of
      bacterial contamination were performed by taking daily water samples at 2,045 key
      sites along the water distribution channels in the cities included in the study.
      In 1996 and 1997, the percentages of samples with good chlorination (residual
      chlorine > or = 0.3 mg/L) for the entire country were 72.4% and 74.8%,
      respectively, whereas the percentages of samples with little bacterial
      contamination (most probable number [MPN] of fecal coliform bacteria < or =
      9.2/100 mL) were 87.0% and 76.5%, respectively. Logistic regression revealed, at
      the local level, an inverse correlation between each of these percentages and the
      number of medical consultations for ADD (per 100,000 inhabitants), although it
      was not statistically significant. These results allowed the authors to stratify
      the cities included in the study according to their different levels of risk for
      ADD: high risk (23 cities), moderate risk (8 cities), and low risk (0 cities).

PMID- 10893972
TI  - Lymphatic filariasis in the Caribbean region: the opportunity for its elimination
      and certification.
AB  - In order to support the case for a certification of elimination of lymphatic
      filariasis (LF) in some Caribbean countries, we compared the prevalence of
      circulating Wuchereria bancrofti antigen in communities in Guyana, Suriname, and
      Trinidad. For the study, we assayed school children in six communities in Guyana,
      five communities in Suriname, and three communities in Trinidad for the
      prevalence of circulating W. bancrofti antigen, using a new immunochromatographic
      test for LF. We also assayed adults in these three countries, with a special
      focus on Blanchisseuse, Trinidad, where mass treatment for LF elimination had
      been carried out in 1981. The prevalences of W. bancrofti circulating antigen
      found in the school children populations ranged from 1.7% to 33.2% in Guyana and
      were 0.22% overall in Suriname and 0.0% in Trinidad. Among adults in two Guyana
      communities the prevalences were 16.7% and 32.1%. The results were all negative
      from 211 adults in communities in the north, center, and south of Trinidad, as
      well as from 29 adults in Suriname. The data suggest that contrary to reports of
      LF endemicity from the World Health Organization, LF may no longer be present in
      Trinidad and may be of very low prevalence in Suriname. Trinidad and Tobago and
      other Caribbean nations proven negative could seek to be awarded a certificate of
      LF elimination. In Suriname the small localized pocket of infected persons who
      may serve as a reservoir of LF infection could be tested and appropriately
      treated to achieve LF elimination. Such LF-positive countries as Guyana should
      access new international resources being made available for LF elimination
      efforts. An adequate certification program would help identify which countries
      should seek the new LF elimination resources.

PMID- 10893973
TI  - [Epidemiology of leptospirosis in a livestock production area of the Andes].
AB  - A cross-sectional study was conducted to estimate the prevalence of Leptospira
      infection in populations of workers, cattle, and pigs in livestock operations and
      to explore some environmental and production system variables associated with
      seropositivity. The research was done between November 1997 and February 1998 in
      the municipality of Don Matias, in the northern part of the department of
      Antioquia, Colombia. The area has a cold climate, and there is a "pigs-grasses
      milk" production system that utilizes pig dung to fertilize grazing pastures. A
      total of 23 farms were studied, and blood samples were obtained from 67 dairy and
      pig-raising workers, 174 dairy cows, 68 pigs for fattening, and 214 pigs for
      breeding. The microagglutination test (MAT) was used for six Leptospira
      serotypes. The seropositivity prevalence was 22.4% among the workers (95%
      confidence interval: 13.1% to 34.2%), 60.9% among the dairy cows (95% CI: 53.2%
      to 68.2%), 10.3% in the fattening pigs, and 25.7% in the breeding pigs. Four
      logistic regression models were constructed to identify the variables that
      predicted infection in the workers and in the dairy cows. A high prevalence of
      infection with Leptospira (serotypes pomona, bratislava, and hardjo) was found in
      this production system, where conditions are favorable for transmitting this
      microorganism to the different animal species and to humans.

PMID- 10893974
TI  - [Epidemiologic aspects of Haemophilus influenzae type b infection].
AB  - This paper reviews the role of Haemophilus influenzae type b (Hib) as one of the
      most important pathogens causing invasive infectious diseases, especially in the
      first 2 years of life. In developing countries H. influenzae is responsible for
      30% of all pneumonia cases with positive cultures and for 20% to 60% of all
      bacterial meningitis cases. In this study we compared Brazilian and international
      epidemiologic data obtained from several bibliographic databases (MEDLINE, 1966
      to 1995; LILACS, 1982 to 1995; Thesis Databank, 1980 to 1995; and Dissertation
      Abstracts, 1988 to 1994). The incidence of Hib infection in Brazil was analyzed
      for individual states and for different ages, including within the first year of
      life. Meningitis cases were used as an incidence marker because of the difficulty
      in identifying the causative organism in such other infections as pneumonia,
      osteomyelitis, epiglottitis, cellulitis, and endocarditis. Our analysis showed
      that the nationwide Brazilian data masked the regional incidence and lethality of
      H. influenzae. For example, in 1991 the national incidence was 18.4 per 100,000
      children under 1 year of age. In the same period, the Federal District had an
      incidence of 175 per 100,000 among children between 4 and 6 months of age.
      Similarly, the North of Brazil had a 35% case fatality rate in 1987, whereas the
      rate was 22% for Brazil as a whole. This study raises issues concerning the
      relevant epidemiologic factors associated with Hib infection and the costs and
      benefits of prophylaxis and vaccination in the age groups most at risk.

PMID- 10893975
TI  - [Comments about the article on cardiovascular risk factors in Chilean college
      students].

PMID- 10893976
TI  - [Re: Social participation in health: a case study in Brazil].

PMID- 10893977
TI  - [Public health and curative medicine: study subjects and disciplinary
      boundaries].

PMID- 10893978
TI  - Assessment of non-response bias in a probability household survey of male same
      gender sexual behavior.
AB  - OBJECTIVE: To assess non-participation bias in a survey of male sexual behavior.
      MATERIAL AND METHODS: A household survey was carried out in 1992-1993 using a
      probability sampling frame in Mexico City. Demographic variables were available
      for all eligible men. The extent of non-participation bias was estimated using a
      version of the Heckman method, which utilizes two equations, one to predict
      participation and the other to predict reports of same-gender sexual behavior.
      RESULTS: A total of 8,068 of the 13,713 eligible men completed a face-to-face
      questionnaire (response rate 59%); 173 men (2.1%) reported bisexual behavior in
      their lifetime, and 37 (0.4%) reported only male partners. Survey participation
      was predicted using demographic variables: 67% of the observations were correctly
      predicted by a probit regression model: 82% of participants and 53% of non
      participants (pseudo-r2 = 0.13). Same-gender sexual behavior was predicted by
      variables indicating attachment to gay/bisexual social networks, history of
      sexually transmitted diseases, positive attitudes towards gay and bisexual males,
      and lack of support from male relatives. Ninety-seven per cent of the cases was
      correctly predicted by the probit model (pseudo-r2 = 0.14). The correlation
      between these two equations was not statistically significant. CONCLUSIONS: These
      results indicate that prevalence estimates of same-gender sexual behavior among
      Mexico City men were not biased by selective survey participation. Careful
      selection and training of household interviewers may have assisted in minimizing
      potential bias.

PMID- 10893979
TI  - [Psychosocial status of adolescents and pregnancy toxemia].
AB  - OBJECTIVE: To compare the perception of psychosocial conditions (during
      pregnancy) between two groups of adolescents; one group was integrated by young
      women diagnosed with pregnancy induced-hypertension and the other group by
      clinically healthy women. MATERIAL AND METHODS: A case-control study design where
      39 cases and 88 controls were chosen from pregnant adolescents seeking care at
      the General Hospital of Durango City, Mexico, from July 1996 to February 1997,
      and from September 1998 to January 1999. Participants agreed to answer a semi
      structured questionnaire to collect data on psychosocial support; psychosocial
      source of stress; coping responses; intention, desire and acceptance of
      pregnancy; and attitude and quality of socialization during pregnancy. Data
      analysis consisted of descriptive statistics, chi 2 and odds ratios with 95%
      confidence intervals. RESULTS: The two groups' sociodemographic and gyneco
      obstetric characteristics were similar. Perception of stressors was higher among
      cases; sources of support were greater among controls. Positive attitudes and
      satisfactory socialization during pregnancy were more frequently reported by
      controls, with statistically significant differences between groups. CONCLUSIONS:
      We found qualitative differences in the perception of psychosocial conditions
      among study participants, with statistically significant favorable perceptions
      among controls.

PMID- 10893980
TI  - [Prevalence of hearing loss and correlated factors in a cement plant].
AB  - OBJECTIVE: To assess the impact of occupational exposure to noise, as well as its
      relationship with other factors that can induce hearing loss. MATERIAL AND
      METHODS: In January and February 1997, we conducted sonometry and dosimetry tests
      in a cement factory, as well as audiometric test in 85 cement workers, to
      identify sources of noise and evaluate the effect to noise exposure and other
      factors, of the prevalence of occupational hearing loss. Statistical analysis was
      conducted using measures of central tendency, bivariate analysis and polynominal
      regression models. RESULTS: High noise levels were found in the crushing, crude
      milling, and cement milling sites. The highest individual dose corresponded to
      the packer job post. Fifty-five per cent of the study population presented some
      degree of hearing loss due to noise exposure. The cement processing area with the
      highest percentage of damaged workers was calcination. CONCLUSIONS: Our results
      show that noise is a serious risk factor in particular sites of cement factories,
      and also that an elevated number of hearing loss cases are due to occupational
      noise exposure in this industry; Our findings underscore the need for designing
      and implementing hearing protection programs, to assure the health and safety of
      cement workers.

PMID- 10893981
TI  - [Breast-feeding training for the nursing staff at the General Hospital of
      Mexico].
AB  - OBJECTIVE: To evaluate the change of knowledge in nurses attending an eighteen
      hour lactation course at the General Hospital of Mexico. MATERIAL AND METHODS:
      The study was conducted from May 1996 to May 1997 and consisted of a
      breastfeeding training course and pre and post-test course evaluations of nurse
      participants. One-hundred-and-forty out of 152 nurses were trained and evaluated.
      Statistical analysis consisted of a paired t-test and analysis of variance.
      RESULTS: Of 152 nurses attending the course, 140 (92%) completed pre and post
      course evaluations. Global results of pre and post-tests were 5.39 +/- 1.37 and
      7.74 +/- 0.79, (p < 0.001). The difference was still significant after we
      compared the instruction level of participants. There was a trend towards a
      higher level of instruction among those with higher knowledge on lactation in the
      post-course evaluation (p = 0.004). CONCLUSIONS: An 18-hour course given to
      nurses significantly increased in knowledge on lactation.

PMID- 10893982
TI  - [Financing of drug addiction programs in Mexico City: 1990-1994].
AB  - OBJECTIVE: To analyze the financial flows in the drug dependency programs in
      Mexico City, their financial source, and the way how funding monies are spent.
      MATERIAL AND METHODS: A discrete number of institutions devoted to drug
      dependency control in Mexico City was selected. Analysis of financial flows was
      carried out using the National Health Accounts methods. Questionnaires to
      quantify resources were applied to health service managers and users. In addition
      to collection of financial flow data, we calculated the expenditures per user for
      each institution. For the period 1990-1993, expenditures were estimated from
      financial budgets allocated to each program in 1990, at constant values to
      eliminate the effects of inflation. RESULTS: Financial sources identified were:
      the federal budget allocation (50-90%), user fees (10-20%), and non-governmental
      organization contributions (15-80%). CONCLUSIONS: Even though budgets in
      participant institutions have increased in the last four years, they are still
      inadequate to cover the large demand of services. It is important to identify new
      ways to increase the availability of resources as well as to ensure their
      efficient use. Continuing financial analysis of these programs will allow the
      assessment of changes to guide optimal financial decision making.

PMID- 10893983
TI  - [Nutritional risk in patients with pulmonary tuberculosis: the patient's or the
      health services' problem?].
AB  - OBJECTIVE: To determine nutritional risk factors in a population of patients with
      pulmonary tuberculosis (PT). MATERIAL AND METHODS: During 1997, one-hundred and
      eighty-five patients with PT were chosen at random from two health institutions
      in Monterrey, Nuevo Leon, Mexico. Variables analyzed were: anthropometric
      measures, socioeconomic status, utilization of the nutrition clinic, access to
      foodstuffs, adverse reactions to drugs, and disease attributable to malnutrition.
      Statistical analysis consisted of descriptive, bivariate, and multivariate
      logistic regression, in addition to prevalence ratios and 95% confidence
      intervals. RESULTS: The mean age was 42.4 +/- 19.9 years. The mean body mass
      index was 19.8 +/- 3.2; 57% of patients presented malnutrition; 26% of them were
      referred to the nutrition clinic, 24.3% of whom actually attended it.
      Multivariate analysis showed that adverse reactions of tuberculosis drugs were
      risk factors for malnutrition, independent of age, gender, education, occupation,
      year of diagnosis and access to foodstuffs, disease attributable, and utilization
      of the nutrition clinic. (chi 2 = 10.58; p = 0.051, R2 = 0.42). CONCLUSIONS:
      Nutritional risk in patients with pulmonary tuberculosis is both a patient and a
      health services issue. The high prevalence of malnutrition, the low utilization
      rate of nutritional services, and the effect of adverse reactions to therapeutic
      drugs, justify the need to focus attention on this particular group of patients.

PMID- 10893984
TI  - [Historical development of epidemiology: is growth as scientific discipline].

PMID- 10893985
TI  - [Epidemiologic study design].

PMID- 10893986
TI  - [Main results of mortality statistics in Mexico, 1998].

PMID- 10893987
TI  - [Report on the use of radiation as intervention action in public health].

PMID- 10893988
TI  - [Call of the International Poverty and Health Network to health professionals].

PMID- 10893989
TI  - [The frontier's science: a new alternative for scientific dissemination in the
      north of Mexico].

PMID- 10893990
TI  - [The National Congress of Vaccination is becoming an Ibero-American congress].

PMID- 10893992
TI  - [In-vitro studies of resin-bonded slot composite bridges compared to
      conventionally prepared composite bridges].

PMID- 10893991
TI  - [Preprosthetic plastic soft-tissue surgery. Vestibular gingival extension with a
      free mucosal graft].

PMID- 10893993
TI  - [Value of manometry].
AB  - Manometry of the esophagus is essential in the diagnostic workup of patients with
      motility disorders of the esophagus. Before manometry organic diseases causing
      the symptoms should be excluded by a esophago-gastroscopy and/or a barium swallow
      meal. Indications for manometry are noncardiac chest pain, dysphagia of unknown
      origin, primary or secondary motility disorders of the esophagus and preoperative
      assessment before antireflux surgery.

PMID- 10893994
TI  - [Therapy of Helicobacter pylori infection].
AB  - H. pylori eradication remains standard treatment for peptic ulcer disease. Until
      now, other indications like non-ulcer dyspepsia, reflux esophagitis, or
      concomitant medication with non-steroidal antirheumatics are not approved
      according to actual guidelines and these patients should be managed on an
      individual basis only. One week triple therapy consisting of a proton-pump
      inhibitor (PPI), a macrolide antibiotic (clarithromycin), and a imidazole
      antibiotic (metronidazole) or amoxicillin, given bid. Quadruple therapy including
      PPI, bismuth, tetracycline and metronidazole should be reserved to eradication
      failures.

PMID- 10893995
TI  - [Non-alcoholic steato-hepatitis].
AB  - The term Non-Alcoholic Steatohepatitis (NASH) was introduced to describe a group
      of patients in whom liver biopsy shows the typical morphology of Alcoholic
      Steatohepatitis, without the presence of any significant alcohol consumption. The
      presence of steatosis and inflammatory infiltrate in liver biopsy is essential
      for the diagnosis of NASH. Other chronic liver diseases--such as Hepatitis B and
      C as well as Autoimmunohepatitis--which can cause similar morphologies have to be
      excluded. The pathophysiology of NASH is essentially still unclear. On the one
      hand toxic effects of oxidated fatty acids are suspected, on the other hand it is
      postulated that the fatty liver is very vulnerable and that actual hepatitis is
      triggered by an additional stressor. The disease has a benign clinical course and
      the typical patient is asymptomatic with elevated liver enzymes. Despite the
      paucity of symptoms the risk of cirrhosis is approximately 8-17%. No established
      treatment exists. Preliminary reports suggest a positive effect of gradual weight
      loss and ursodeoxycholic-acid but further studies are needed to confirm this
      observation.

PMID- 10893996
TI  - [Therapy of problem cases in hepatitis B].
AB  - In the management of hepatitis B new therapeutic options have been established in
      the last years. Patients with fulminant course are rarely observed and should be
      submitted in a hepatological center. In chronic hepatitis B today we see mainly
      HBeAg negative/anti-HBe positive patients with replication of HBV-mutants. The
      tendency is to treat these cases with lamivudine (LAM) for some years. This is
      also true for HBV-cirrhosis in stage Child A. The progressed cirrhosis (Child
      B/C) without option for liver transplantation is not an indication for
      nucleosidanaloga and a contraindication for interferon. However before liver
      transplantation the viraemia should be diminished lower than 5 pg/ml. That means
      the HBV-hybridization test should become negative, which can be achieved with LAM
      in most cases. During and after liver transplantation the HBV-infected patients
      receive passive immunoprophylaxis with anti-HBs-hyperimmunoglobulin. In the
      situation of reinfection and hepatitis, nucleosidanaloga are indicated, in the
      first line LAM. In the case of LAM-resistance, interferon alpha is a further
      option. Patients after renal transplantation and HBV-infection should also be
      treated with LAM. In these patients IFN should be avoided, because graft
      rejection can be induced. Combined infection with HBV plus HDV, HCV or HIV need
      an individual concept for treatment. Extrahepatic manifestations of HBV-infection
      with clinical relevance, e.g. panarteriitis or glomerulonephritis are indications
      for antiviral treatment. If treatment with glucocorticosteroids is necessary in
      these situations, the steroids should be given only in combination with LAM. In
      non-cirrhotic patients with normal aminotransferases but quantify-able viraemia
      the liver histology is helpful for the indication of treatment.

PMID- 10893997
TI  - [Value of mini-laparoscopy].
AB  - Mini-laparoscopy uses 1.9 mm diameter optical instruments allowing examination of
      the abdomen following a single puncture. It is an extremely safe and only
      minimally invasive technique allowing accurate staging of liver disease as well
      as sensitive detection of tumor dissemination. It can be performed as an
      outpatient procedure. Its most common indication is for accurate staging of liver
      fibrosis, where it is much superior to all other techniques.

PMID- 10893998
TI  - [Therapy of primary sclerosing cholangitis].
AB  - In primary sclerosing cholangitis the aim of treatment is a reduction of the
      inflammatory destruction of the bile ducts leading to cholestasis and
      irreversible liver damage. Treatment with ursodeoxycholic acid may decrease the
      periductular inflammation. Bacterial infection of the bile ducts is frequent and
      should be treated by antibiotics. Medical treatment of the disease may be
      successful under the assumption that dominant stenoses are treated
      endoscopically.

PMID- 10893999
TI  - A pilot study of verbal fluency in the Zulu speaking population with preliminary
      application to traumatic brain injury.
AB  - This study investigated the semantic verbal fluency (VF) abilities of non
      neurologically impaired (NNI) Zulu speaking subjects in order to obtain normative
      data for this population. The data were analysed in terms of the total number of
      words generated in one minute, the number of words generated over four fifteen
      second time periods and the strategies employed. Where possible, these results
      were compared to performance of South African English speaking NNI subjects. The
      responses of three traumatically brain injured (TBI) Zulu speaking subjects on VF
      tasks were obtained and compared to the NNI subjects. The NNI subjects performed
      significantly poorer than the current norms and poorer than the South African
      English speaking population. The TBI subjects generated fewer words than the NNI
      subjects. The strategies used by the TBI subjects were similar in type but were
      less efficiently used than the Zulu speaking NNI subjects. The results of this
      study are particularly relevant to the clinical role of speech pathologists in
      the multicultural and multilingual population of South Africa.

PMID- 10894000
TI  - Early communication intervention within a community-based intervention model in
      South Africa.
AB  - Infants and toddlers with special needs within the developing context in South
      Africa are not currently receiving adequate early communication intervention
      services. The development of a model for service delivery to this population is
      imperative for the successful implementation of early communication intervention
      in the developing context in South Africa. The basic model of early intervention
      service delivery provides a theoretical basis for early intervention service
      delivery but has certain limitations when applied to the developing context in
      South Africa. Community-based intervention is proposed as an avenue for the
      delivery of health care services within primary health care although constraints
      in the application of community-based intervention exist. An integrated model of
      early communication intervention service delivery within community-based
      intervention is proposed and illustrated by presenting a case example.

PMID- 10894001
TI  - [Speech understandability test in Sepedi].
AB  - The aim of this study was to develop the "Sepedi-toets vir
      Spraakverstaanbaarheid" to objectively evaluate the speech intelligibility of the
      client and to give appropriate phonetic information. This study evolved from the
      present need for evaluation mechanisms and therapeutic services in the indigenous
      African languages. The words used in the test had to conform to the requirements
      of certain phonetic criteria. Words and sentences of differing lengths were
      included. The procedures followed by the test administrator were different for
      mother tongue speakers than those for non-mother tongue speakers. After the
      compilation of the test it was applied to four dysarthria speakers. Upon
      execution of the test it was evident that differences in judgment of speech
      intelligibility exist between mother tongue and non-mother tongue speakers.
      Useful phonetic information was obtained through the qualitative analysis of the
      speech productions. It appears that the "Sepedi-toets vir Spraakverstaanbaarheid"
      can be used in the clinical environment to obtain a more objective evaluation of
      the client.

PMID- 10894002
TI  - Story grammar analysis of pre-schoolers' narratives: an investigation into the
      influence of task parameters.
AB  - This study aimed at examining the influences of the parameters of the narrative
      task (administered to the pre-schooler) on narrative structure. Seventeen pre
      school children were selected as subjects. Five narrative tasks were administered
      to each subject. The narratives were analysed for length and structure. Mainly
      two factors were found to influence the length and structure of the produced
      narratives; firstly, the presence or absence of a 'model' on which the child
      could base his/her narrative, and, secondly, the structure inherent in this
      'model'. The implications of the study for clinical assessment of narrative
      skills as well as for further research are considered.

PMID- 10894003
TI  - Narrative discourse productions in older language impaired learning disabled
      children: employing stricter reliability measures.
AB  - This study aimed to describe narrative discourse productions of older language
      impaired learning disabled (LILD) children, using stringent reliability measures.
      Coherence and cohesion were the measures of analysis employed. Content and
      clarity ratings provided a subjective analysis of narrative productions.
      Interrater and intrarater reliability measures were calculated and testing for
      stability of scores across three testing sessions were undertaken. The results
      indicated subtle differences in the coherence and cohesion of narrative
      productions in the LILD compared with controls. The findings of this study
      support past literature, which calls for greater research in this area using
      stricter reliability measures.

PMID- 10894004
TI  - Swallowing problems in the normal ageing population.
AB  - This study investigated the prevalence of subjectively reported swallowing
      problems in a group of normal ageing subjects. Twenty-five retirement village
      residents were included in the sample. A cross-sectional descriptive survey
      research design was utilised. Data was obtained through the administration of a
      devised interview schedule. The prevalence of reported swallowing problems in the
      sample was determined. The nature of the swallowing problems were examined and
      compared to those reported to occur in the normal ageing population. The utility
      of the interview schedule was critically evaluated. Results revealed an overall
      prevalence of 44% of subjects who experience swallowing problems that interfere
      with their day to day functioning. Of these, 64% experienced swallowing
      difficulties affecting all phases of the swallow while 36% experienced
      difficulties affecting the pharyngeal and oesophageal phases. The interview was
      found to be a useful screening measure in identifying the presence of swallowing
      problems. The role of the speech pathologist in dysphagia in the normal ageing
      population is highlighted and justified.

PMID- 10894005
TI  - [Suprasegmental speech in prelingual hearing-impaired children with cochlear
      implants, hearing-impaired children without implants and normal hearing
      children].
AB  - A review of the relevant literature indicates a lack of knowledge regarding
      suprasegmental speech characteristics in prelingual hearing impaired children
      with cochlear implants. This study is aimed at examining certain suprasegmental
      features in the speech of prelingual hearing impaired children with cochlear
      implants by perceptual ratings and acoustic analyses, comparing these results to
      that of prelingual hearing impaired children without implants, and normal hearing
      children of the same age. Twelve Afrikaansspeaking children between the ages of
      six and ten years were included in three groups. An integrated view of the
      perceptual and acoustic results shows that the cochlear implanted children's
      suprasegmental speech characteristics bear closer resemblance to those of the
      normal hearing group than those of the hearing impaired group.

PMID- 10894006
TI  - The impact of a digital speaker on a teacher's interaction with a child with
      limited functional speech.
AB  - This paper describes the impact of the implementation of a digital speaker and
      teacher training on the quality of a teacher's interaction with an AAC user. The
      data was obtained by recording and analysing classroom story time interactions.
      The types of utterances directed at each child in the class, the types of
      questions used as well as the messages recorded onto the digital speaker were
      determined for each research phase. There were four major phases in the research,
      namely, a pre-implementation phase, a post-implementation phase, a post-training
      phase and a post-withdrawal phase. The results indicated that the implementation
      of the digital speaker and the training of the teacher resulted in certain
      changes in the way that the teacher interacted with the AAC user. Utterance types
      such as answering and imitating were used more frequently after the
      implementation of the device. There was also a much greater variety in the
      teacher's use of questions as well as in the messages that were recorded onto the
      digital speaker after the five training sessions were completed. This study
      highlighted the importance of formal training for the communication partners of
      the AAC user. One of the most important communication partners of the school-aged
      AAC user is the classroom teacher.

PMID- 10894007
TI  - A model of frequency coding in the central auditory nervous system.
AB  - A phenomenological model for neural coding in the central auditory system is
      presented. This model is based on average rate-place codes and the hypothesis is
      that the rate-place code present in the population of low spontaneous rate nerve
      fibres is adequate to account for frequency discrimination thresholds across the
      entire audible frequency range. The activity of a population of nerve fibres in
      response to an input pure tone is calculated and a neural spike train pattern is
      generated. An optimal central observer estimates the input frequency from the
      spike train pattern. The model output is the frequency difference limen at the
      specific input frequency, determined from the estimated input frequency. It is
      shown that a rate-place code can account for psychoacoustically observed
      frequency difference limens. The model also supports the hypothesis that a human
      listener does not make full use of all the information relevant to frequency that
      is available in auditory nerve spike trains.

PMID- 10894008
TI  - The auditory brainstem response--are South African ENT's missing the point?
AB  - The use and misuse of the auditory brainstem response (ABR) test by hearing
      professionals is often related to the extent and nature of the training they have
      received. This study used a postal survey based questionnaire to investigate the
      levels of training in, knowledge about, and appropriateness of referral for, ABR
      testing in Ear, Nose and Throat (ENT) surgeons and registrars in Gauteng, South
      Africa. Thirty-seven actively practising ENT specialists and registrars were
      sampled using a convenience sampling technique. Overall, a poor level of training
      and knowledge in ABR and its related areas of audiology was identified. This was
      mirrored by a high demand for further education. Considering the prevalence of
      auditory disorders in South Africa, and the push towards primary care and early
      intervention, this study's results highlight the need for improved training in
      ABR for ENT surgeons and registrars.

PMID- 10894009
TI  - [Is appendectomy really performed too frequently? Results of the prospective
      multicenter study of the Swiss Society of General Surgery].
AB  - Scientific publications and provoking criticism from the lay press have recently
      pointed out, that appendices may be surgically removed too frequent and without
      indisputable necessity. In an attempt to verify these questionable statements,
      the Swiss Society for General Surgery (SGAC) initiated a prospective controlled
      multi center trial. From September 1997 to December 1998, hundred and twenty-five
      institutions documented 4603 appendectomies performed due to a suspected
      appendicitis. Histological investigation of all specimens revealed a 7% rate of
      normal appendices, 7.2% for patients with national health service (NHS) and 5.9%
      for patients with private insurances respectively. Compared to the results of the
      literature, where a frequency of normal appendices around 15% is judged as
      standard, these results are excellent. In 17.2% of the patients (15.9% NHS and
      23.6% privately insured patients) an "appendicitis perforata" was observed. This
      percentage remains in the range reported by other authors. The analysis of time
      of admission (i.e. day or night) and the delay from admission to surgery shows a
      distribution independent to the insurance of the patients. Therefore, the planned
      appendectomy for patients with private insurances does not exist. A different
      choice of the surgical technique could be observed depending on the insurance
      status. In 30.4% of the private insured patients a laparoscopic appendectomy was
      performed as compared to 22.6% of patients with NHS. Surprisingly, an identical
      median hospitalization time can be observed for both groups (laparoscopic 5.5
      days, open surgery 5.5 days).

PMID- 10894010
TI  - Stereotaxic vacuum core breast biopsy--experience of 560 patients.
AB  - The purpose of our study was the assessment of the diagnostic value of vacuum
      core biopsy, which promises high accuracy. The material used were a digital
      stereotaxic biopsy table (Fischer Imaging) and a Mammotome-gun (Biopsys). A total
      of 560 patients with 594 predominantly indeterminate lesions underwent vacuum
      core biopsy (VCB). Verification was a follows: (a) demonstration of complete or
      partial removal of the lesion or replacement of the lesion by a small hematoma by
      comparison of the pre- and post-VCB mammogram; (b) reexcision of 105 malignant
      and 13 borderline lesions; (c) radiologic-histologic correlation; (d) 6-month
      follow-up mammograms in 460 cases. Five puncture errors occurred which, however,
      were immediately recognized and VCB was repeated. Based on the above verification
      a 100% accuracy was achieved. Only one relevant hematoma that required surgical
      excision occurred. Except for one case mammographically any severe scaring was
      visible. Based on the excellent accuracy and excellent tolerance of the procedure
      VCB appears to be the future method of choice for the workup of those
      indeterminate mammographically detected lesions that up to now have still
      required surgical biopsy.

PMID- 10894012
TI  - [Small breast carcinomas--less axillary surgery?].
AB  - In view of introducing less invasive or selective axillary procedures for small
      breast cancers we investigated our own pT1 tumor patients. The incidence of pT1
      carcinoma, the nodal involvement of pT1a, b and c, the axillary relapse and the
      overall survival were analyzed. From 1983 till 1997 185 consecutive patients have
      been treated for breast cancers with a diameter of < or = 20 mm. The survival
      data after Kaplan-Meier are based on a cohort of 117 patients with a median
      follow up of at least seven years. There were seven patients with a pT1a
      carcinoma, 30 with a pT1b and 148 with pT1c carcinoma. On an average 16 axillary
      lymph nodes were counted by the pathologists. The axillary involvement clearly
      depends on the size of the primary tumor: no nodal involvement in patients with
      pT1a carcinoma, 10% in patients with pT1b carcinoma and 30% in patients with pT1c
      carcinoma. Not one single axillary relapse was detected after this follow up
      time. The overall ten years survival for patients with pT1a was 100%, 91% for
      pT1b, but only 74% for pT1c carcinoma. Screening mammography is expected to
      detect more small breast cancers in pN0 stage. Risks and benefits of axillary
      dissection have to be carefully evaluated. Axillary involvement of small breast
      cancers is rare. Only a minority of patients will benefit from routine axillary
      lymphadenectomy, while the majority runs the risk of complications. The sentinel
      lymph node (SLN) procedure offers a selective approach to this dilemma.

PMID- 10894011
TI  - [The Advanced Breast Biopsy Instrumentation (ABBI) for evaluation of
      mammographically suspicious, non-palpable findings of the breast: a reliable
      diagnosis with minor therapeutic potential].
AB  - BACKGROUND: Stereotactic biopsy techniques supersede conventional hook-wire
      localization followed by open excision to clarify the dignity of nonpalpable
      mammographic lesions. The advanced breast biopsy instrumentation (ABBI) allows
      stereotactically guided excision of a specimen up to 20 mm in diameter on an
      outpatient basis under local anaesthesia. METHODS: Demographic information,
      mammographic and pathological findings, complications, subsequent interventions
      and sensitivity as well as efficiency of a series of 144 planned ABBI procedures
      were documented (largest published single institution series). RESULTS: The ABBI
      procedure was successfully performed in 93.8% (135/144); accurate diagnosis was
      made in 99.3% (134/135), sensitivity for malignant lesions was 96.9% (31/32) and
      morbidity was 1.5%. Consistent with other published series margins of the biopsy
      cylinder containing a malignant lesion were involved in 83.9% (26/31).
      CONCLUSIONS: Excisional biopsy using the ABBI system is a reliable diagnostic
      tool with a low incidence of morbidity. The therapeutic use is of limited
      potential.

PMID- 10894013
TI  - [Significance of endoscopic axillary dissection in invasive breast carcinoma
      after introduction of the "sentinel lymph node" method].
AB  - Axillary clearance provides prognostic information, determines adjuvant therapy
      and reduces axillary recurrences. However significant morbidity may follow
      axillary dissection. Patients with small tumors (pT1a-c) may benefit from new
      less invasive (endoscopic lymph node dissection) or more selective (sentinel
      lymph node biopsy) axillary procedures which recently have been introduced. In
      this prospective study the axilloscopic approach was evaluated. PATIENTS AND
      METHODS: 55 clinically node negative patients (mean age: 60 years [30-86]) had
      endoscopic axillary surgery by one single surgeon (1.1996-6.1998). After axillary
      liposuction individual lymph nodes (level I + II) were identified and removed
      under direct vision by means of a laparoscope (successful procedure in 95%; n =
      52). Patients were followed every four months according to a institution based
      follow up protocol. Results of 51 patients (1 refused) were analyzed after a
      median follow up of 22 (7-37) months by self-evaluation questionnaire, interview
      and clinical examination (including: range of motion of the shoulder joint,
      circumferences of the upper extremities). RESULTS: An average of 13.3 (5-25)
      lymph nodes was endoscopically removed. Patients (n = 16; 31%) had involved nodes
      with a mean of 3.1 nodes positive per individuum. Seromas necessitated needle
      aspiration in 8 patients (15%). There were no hematomas and one low grade
      infection (2%). After a median follow up period of 22 (7-37) months no axillary
      relapse but one trocar site implantation metastasis (1/55, 2%) was detected and
      resected. No lymph edema was observed. Early range of motion of the shoulder
      joint was excellent. CONCLUSION: This technique allows the removal of an adequate
      number of lymph nodes for staging as well as for regional control. The morbidity
      is low and the medium-term follow-up results are promising. The atraumatic and
      very well tolerated endoscopic axillary dissection is being replaced by the
      selective sentinel lymph node procedure.

PMID- 10894014
TI  - [Validation study of the sentinel lymph node (SLN) method in invasive breast
      carcinoma. Personal data and review of the literature].
AB  - BACKGROUND: Axillary lymph node dissection (ALND) is an integral part in the
      therapy of breast cancer. Axillary lymph node involvement and tumour size are the
      most important prognostic factors. Restriction of ALND to level I and II (Berg)
      reduced high morbidity. The increasing proportion of patients with early breast
      cancer and negative axillary nodes led to a more selective method to avoid
      unnecessary ALND. The sentinel lymph node (SLN)--the first draining lymph node of
      a tumour--represents the status of the axilla. A negative SLN prevents from
      further completion ALND. PATIENTS AND METHODS: From 9/97 to 1/99 44 patients with
      invasive breast cancer underwent a prospective trial of lymphatic mapping with
      isosulfanblue and/or lymphoscintigraphy with 99m technetium-labelled human
      colloid. During the operation a hand-held gamma probe was used for detection. The
      SLN was removed selectively and examined by routine histopathology (H&E) and
      immunohistochemistry (IHC). ALND of level I and II was performed in all patients
      for correlation. RESULTS: The SLN were identified in 41 of 44 patients (93%). 2.4
      SLN per patient were harvested, overall 17.6 axillary lymph nodes. Of the 41
      patients, 21 patients had positive, 20 patients negative SLN. In the 20 patients
      with negative SLN only one patient (5%) had metastatic disease on complete
      dissection (negative predictive value of 95%). In 17 patients with positive
      axillary lymph nodes 16 were found to have positive SLN, only one SLN was
      negative (false negative rate of 5.9%). In two of 41 patients micrometastases
      were detected by IHC. Lymphoscintigraphy revealed drainage to the axilla and
      internal mammary nodes in two of 28 cases (7%). SUMMARY: Our validation study
      proves the reproducibility and reliability of the SLN procedure. A
      multidisciplinary approach is indispensable. The SLN procedure has the potency
      for becoming the selection criterion whether to perform an ALND or not. Multiple
      sections and IHC staining improve the detection rate of metastatic disease.
      Ongoing long time investigations will determine the impact on overall survival.
      Our own data are discussed in an extended review of the literature.

PMID- 10894015
TI  - [Neoadjuvant therapy in breast carcinoma].
AB  - The preoperative or neoadjuvant chemo- or endocrine therapy in the treatment of
      locally advanced breast cancer is a new therapy option. Clinical Studies could
      show, that there is no difference in overall survival between patients, who
      received a preoperative chemotherapy and patients, treated with the
      conventionally postoperative, adjuvant chemotherapy. There is an increased rate
      of breast conserving therapy for the locally advanced breast cancer because of
      tumor shrinking. Neoadjuvant chemotherapy is also a good in-vivo-model for
      chemosensitivity-testing. For elderly patients with comorbidity, the primary
      treatment with endocrine therapy with tamoxifen or aromatase inhibitors could
      even avoid an operation in some cases. The most effective drugs for preoperative
      chemotherapy are anthracyclines and taxanes. The assessment of predictive factors
      like S-phase, Ki67, ploidy, c-erb-B2, in-vitro-chemosensitivity-testing results
      and others could help to differentiate patients who will have a benefit from
      chemotherapy. It is important to have more results from studies with a long term
      follow-up, before we declare primary systemic chemo- or hormone therapy as
      standard therapy for breast cancer patients with locally advanced breast cancer.

PMID- 10894016
TI  - [Diuretics and electrolytes].

PMID- 10894017
TI  - [Pharmacologic action of diuretics in the kidney].
AB  - The currently available diuretics increase the urinary excretion of sodium
      chloride by selective inhibition of specific sodium transporters in the loop of
      Henle and distal nephron. In recent years, the molecular cloning of the distal
      diuretic-sensitive sodium transporters has improved our understanding of the
      cellular mechanisms of action of each class of diuretics. The identification of
      mutations in the genes encoding these transporters in inherited disorders
      characterized by altered salt balance has provided unequivocal evidence for the
      roles of the cloned diuretic-sensitive transporters in sodium homeostasis. The
      biochemical abnormalities observed in these disorders are identical to those
      induced by the specific diuretic. In the Guibaud-Vainsel syndrome (renal-tubular
      acidosis with osteopetrosis) the renal disturbances are comparable to the effects
      of a therapy with acetazolamide. Mutations in the proximal tubular carbonic
      anhydrase type II are the cause of this rare disorder. Bartter syndrome shows
      identical biochemical abnormalities as those found with chronic furosemide
      therapy. This syndrome is caused by mutations in the furosemide-sensitive Na-K
      2Cl cotransporter in the thick ascending loop of Henle. In Gitelman syndrome the
      characteristic electrolyte and hormonal changes in blood and urine are comparable
      to those observed in patients treated with thiazide diuretics. This disorder
      results from mutations in the distal-tubular thiazide-sensitive Na-Cl
      cotransporter. The two forms of pseudhypoaldosteronism are distinguished by the
      characteristic metabolic changes encountered with a therapy with potassium
      sparing diuretics. The genetic disturbance resides either in the amiloride
      sensitive epithelial sodium channel (autosomal-dominant form) or in the
      spironolactone-sensitive mineralocorticoid receptor (autosomal-recessive form) in
      the distal tubule and cortical collecting duct. Current research concentrates on
      defining the structural sites for electrolyte transport and diuretic binding, as
      well as the molecular mechanisms of transport regulation. This information may
      allow a more appropriate use of diuretics and the design of new substances with
      diuretic action.

PMID- 10894018
TI  - [Inhibition of renal carbonic anhydrase as a respiratory stimulant-- an obsolete
      indication?].
AB  - Inhibition of carbonic anhydrase in general or specific inhibition of one the
      different isoenzymes results in a significant metabolic acidosis due to renal
      bicarbonate loss. The increase of arterial pCO2 stimulates central and peripheral
      chemoreceptors and enhances ventilation. The inhibition of carbonic anhydrase as
      a respiratory stimulant is an accepted measure for the prevention of acute
      mountain sickness, has been used for a restricted number of subjects with sleep
      disordered breathing or chronic hypoxaemic lung disease. The few indications and
      the narrow therapeutic index restrict the use of carbonic anhydrase blockers as
      stimulants for ventilation.

PMID- 10894019
TI  - [Rational diuretic therapy in patients with liver cirrhosis].
AB  - When ascites develops in a patient with liver cirrhosis his probability to
      survive the following two years amounts to 50%. It is determined essentially by
      the residual functional capacity of the liver. In 80 to 90% of patients ascites
      due to portal hypertension can be managed by salt restriction and diuretics. A
      daily reduction of body weight of 0.5 to 0.75 kg should not be exceeded because
      prerenal failure may become a threat. Aldosterone-antagonists are more efficient
      and have fewer side-effects than loop diuretics. The urinary ratio of Na/K may be
      used to adjust the therapy. They may lower portal hypertension by an additional
      direct effect on the vasculature. If diuretics are insufficient or when a rapid
      therapeutic success is needed, paracentesis of 4-6 l is a safe option if
      intravascular volume is substituted simultaneously with albumin. Only in the few
      patients whose ascites is intractable by the forementioned measures, alternatives
      such as peritoneo-, venous or porto-systemic shunts (nowadays mostly by
      interventional techniques via a transjugular catheter) should be evaluated. The
      only treatment which not only attacks ascites symptomatically but also corrects
      the underlying disease is liver transplantation.

PMID- 10894020
TI  - [Diuretics and kidney diseases].
AB  - The main indications for diuretic treatment of renal patients are edema and
      hypertension. Pharmacokinetics and pharmacodynamics of diuretics are altered in
      patients with proteinuria and/or impaired renal function. These patients exhibit
      avid sodium retention. Diuretics are partially inactivated by binding to proteins
      in tubular fluid. The natriuretic response to diuretics is limited by counter
      regulation, specifically increased proximal tubular reabsorption in response to
      hypovolemia and increased distal tubular sodium reabsorption in response to
      increased sodium load. At higher serum creatinine values, thiazides are no longer
      sufficiently effective in monotherapy. The diuretics of first choice are then
      loop diuretics, potentially in combination with thiazide diuretics. Potassium
      sparing diuretics are contraindicated. The most important side effects of
      diuretics are hypovolemia with orthostatic hypotension, hypokalemia, metabolic
      alkalosis, increase of creatinine concentration and (rarely) hyponatremia.
      Diuretic treatment should be accompanied by reduction of dietary sodium intake.
      Important points are selection of an adequate dose (in problematic cases dose
      finding via urine sodium measurements) and selection of proper dosing intervals.
      If cases do not respond to loop diuretic monotherapy, combination with thiazide
      diuretics or intravenous administration of loop diuretics should be considered.

PMID- 10894021
TI  - [Diuretic therapy of hypertensives with Type 2 diabetes; rational therapy or
      malpractice?].
AB  - There is overwhelming evidence that effective antihypertensive therapy with
      diuretics reduces total mortality and cardiovascular morbidity. Therefore,
      diuretics have a well established place in the pharmacotherapy of hypertension.
      However, their role in the treatment of hypertensives with type-II-diabetes is a
      matter of controversy due to their potentially adverse effects on glucose-, lipid
      and electrolyte metabolism which--in type-II-diabetics--may potentially offset
      the beneficial effects of blood pressure lowering. However, results of large
      scale, prospective, randomised intervention trials demonstrate that in type-II
      diabetics the beneficial effects of blood pressure reduction per se are more
      important than any potentially adverse effects on metabolic surrogate parameters.
      The reduction in total mortality and cardiovascular morbidity as a result of
      effective antihypertensive therapy is more pronounced in type-II-diabetics than
      in non-diabetics. This holds also true for a diuretic based antihypertensive
      therapy in type-II-diabetics. Clearly their effects on glucose-, lipid- and
      electrolyte metabolism are of minor, if any, clinical relevance. The hypertensive
      type-II-diabetic benefits from diuretics--they prolong life and improve its
      quality. Therefore, antihypertensive therapy with diuretics constitutes a
      rational pharmacotherapy founded on the principles of evidence based medicine and
      must not be considered as malpractice.

PMID- 10894022
TI  - [Diuretic therapy in congestive heart failure--new views on spironolactone
      therapy].
AB  - Cardiac pump failure leads to a reduction of the effective arterial volume. This
      is sensed by the kidney via afferent sympathetic fibres. The renal response to
      the perceived lack of volume is the retention of sodium and water. Although
      initially homeostatic, this renal counterregulation is maladaptive later on and
      may contribute to further cardiac compromise by increasing preload (volume
      retention) and afterload (hyperreninism). The renal sodium retention in
      congestive heart failure is a consequence of the activation of the sympathetic
      nervous system and of the renin-angiotensin-aldosterone system. The retention of
      osmotically free water is partly caused by the nonosmotic secretion of
      antidiuretic hormone from the posterior pituitary and partly by a diminished
      osmoregulatory capacity of the kidney due to diuretic therapy and/or (pre-)renal
      insufficiency. In the near future specific blocking drugs of vasopressin
      receptors should become available which could make a significant contribution to
      the management of hyponatremia in this setting. For the management of
      extracellular volume overload a negative sodium balance is the central objective.
      A moderate reduction of sodium intake is helpful to achieve this goal and has the
      additional benefit of reducing thirst and renal potassium loss. However, the
      majority of patients require (loop) diuretics in addition. Patients who are
      refractory to high and repeated doses of loop diuretics may respond to a
      combination of diuretics which act on different nephron segments. Diuretics
      increase the risk of hypokalemia which can trigger life-threatening
      tachyarrhythmia, particularly in patients with cardiac dysfunction. Hypokalemia
      is therefore an indicator of an adverse outcome. Secondary hyperaldosteronism-
      which can persist despite effective therapy with ACE-inhibitors--is the major
      cause of hypokalemia in this setting. The randomized aldactone evaluation study
      (RALES) has shown that spironolactone (25 mg/day) reduced the risk of hypokalemia
      and decreased morbidity, mortality and clinical symptoms in patients with heart
      failure. The recent encouraging results with vasopressin receptor antagonists and
      spironolactone point to the fact that the therapeutic modification of maladaptive
      homeostatic renal mechanisms plays an increasingly important role in the modern
      diuretic management of heart failure beyond symptomatic relief from volume
      overload.

PMID- 10894023
TI  - [Which hypertensive patient requires diuretic therapy?].
AB  - Over the last decade the role of diuretics as first-line agents for the treatment
      of hypertension has diminished substantially. The present review encourages the
      reader to reconsider the current trend for a decline in the use of these
      inexpensive antihypertensive drugs whose efficacy is well documented. Diuretics
      have been used in 16 placebo controlled studies with over 13,000 patients as
      first-line drugs to lower blood pressure. These drugs were shown to reduce total
      mortality by 11%, cerebrovascular events by 34% and coronary morbidity by 29%.
      The magnitude of blood pressure reduction with low-dose thiazide diuretics is
      comparable to that of a therapy with high-dose thiazides, without the serious
      metabolic side effects observed with the higher dosage. In combination with other
      antihypertensive agents, diuretics counteract the compensatory regulatory
      responses, such as volume expansion and edema formation. Moreover, it has been
      shown that a combination with low-dose thiazides may not only further decrease
      blood pressure but also reduce cerebrovascular and coronary mortality. Advantages
      of diuretics in the treatment of hypertension can be appreciated in special
      clinical conditions, for instance in patients with edema, heart failure, renal
      failure, nephrotic syndrome and portal hypertension. Low-dose diuretics still
      have a place as first-line drugs for the treatment of mild, uncomplicated
      essential hypertension. Moreover, as opposed to other blood pressure lowering
      agents, there is sufficient scientific evidence for the primary preventive effect
      of low-dose thiazide.

PMID- 10894024
TI  - [Standard bicarbonate and base excess--obsolete parameters!].
AB  - The various techniques of interpretation of acid-base disorders are reviewed with
      special reference to the in vitro generated parameters 'standard bicarbonate' and
      'base excess' on one hand and to the application of in vivo physiological data on
      the different acid-base disturbances on the other hand. The pivotal assumption
      that in vitro titration of PCO2 in whole blood (needed for estimation of standard
      bicarbonate and base excess) is representative for the in vivo behavior of the
      intact organism lacks any supportive evidence. The more serious pitfalls of
      interpretating acid-base problems by use of standard bicarbonate and base excess
      can be: 1. Inaccurate identification of the severity of an underlying acid-base
      disturbance, 2. Inadequate estimation of the time course of adaptation to an acid
      base disorder (acute versus chronic) and 3. Failure to identify mixed acid-base
      disorders. Therefore, it is strongly recommended to use the traditional
      parameters (pH, PCO2, bicarbonate) in the light of the wealth of physiological in
      vivo data that form a sound basis for accurate clinical diagnosis.

PMID- 10894025
TI  - [Hypercalcemia].
AB  - Hypercalcemia may develop as a consequence of a disturbance of one or more links
      within the feedback system of calcium homeostasis. Hypercalcemic diseases may be
      caused by the parathyroid glands as well as by their dependent end organs, the
      kidneys, the intestine, the skeleton. Partial parathyroid hormone activity can be
      produced by many tumour factors in a paraneoplastic way. Hypercalcemia induces
      the symptoms of the so-called hypercalcemic syndrome which should be familiar to
      the physician. Hints towards the cause may be the organ manifestation in case of
      primary hyperparathyroidism, in case of the other causal diseases they may
      present with typical components of their clinical picture. Diagnostics should
      start with the differentiation between parathyroid-related hypercalcemia
      (autonomous, primary hyperparathyroidism and variants) and the broad spectrum of
      non-parathyroid hypercalcemia, mainly accompanying malignancies. Symptomatic
      treatment of hypercalcemia often has to start before the definite diagnosis is
      confirmed. Later on, this merely symptomatic treatment may be replaced by causal
      treatment, as far as possible. Symptomatic treatment of hypercalcemia may follow
      the 'diuretic', the 'antiresorptive', or the 'antiabsorptive' way--the
      'extractive' way by hemodialysis is the treatment of choice in case of
      hypercalcemic crisis accompanied by renal insufficiency.

PMID- 10894026
TI  - [Cardiac risks of hypokalemia and hypomagnesemia].
AB  - During treatment with low to moderate doses of thiazides or loop diuretics,
      hypokalemia is dose-dependently demonstrated in 2-11% of patients. Additional
      hypomagnesemia is present in about 40% of hypokalemic patients. High doses of
      diuretics were routinely used in the past for treatment of hypertension or
      heartfailure, causing ventricular arrhythmias and sudden cardiac death. Low-dose
      thiazides +/- potassium-sparing diuretic are not associated with these severe
      adverse effects, but improve in contrast (to high-dose diuretics) survival and
      cardiovascular morbidity in hypertensive patients. Higher doses of diuretics
      often necessary in the treatment of patients with severe heart failure are today
      no longer regularly associated with hypokalemia/hypomagnesemia because of the
      concomitant treatment with an ACE inhibitor and low-doses of spironolactone.

PMID- 10894027
TI  - [Hyponatremia--with comments on hypernatremia].
AB  - Disorders of the serum sodium concentration (hypo- and hypernatremia) are amongst
      the most frequent electrolyte disorders in clinical medicine. They are
      attributable to disturbance of to water metabolism. Hyponatremia is almost always
      a condition of water excess while hypernatremia is due water deficiency.
      Physiological normonatremia (normal plasma osmolality) is maintained by an
      integrated system involving regulated water intake via thirst and control of
      water excretion via antidiuretic hormone secretion. Therefore hypo- and
      hypernatremia should be analyzed in terms of dysregulated ADH secretion, fluid
      intake and renal water excretion. Hyponatremia is usually a disorder of
      vasopressin excess, due to 'non-osmotic' vasopressin release. The latter may
      occur in two different settings: (I) SIADH, (II) baroreceptor mediated
      vasopressin secretion (cardiac failure, liver cirrhosis). This entities are easy
      to distinguish in clinical practice. SIADH is associated with striking lower
      plasma concentrations of urate, creatinine and urea. In SIADH the blood pressure
      is normal and there is no edema. In contrast in the hyponatremia of liver
      cirrhosis and heart failure the plasma measurements indicated are usually
      slightly elevated, the blood pressure is low and there is edema. The typical
      patient with hypernatremia is old and has no thirst sensation. Hypo- or
      hypernatremia may cause major neurologic symptoms. These symptoms are more
      related to the rate of change in the serum sodium concentration than to the
      absolute level of a hypo- or hypernatremia reached. The traditional treatment for
      hyponatremia used to be water restriction. However V2-Vasopressin-Antagonists may
      provide a better treatment modality in the future. Hypernatremia is treated by
      slow rehydratation.

PMID- 10894028
TI  - [Potential dangers of diuretics...].
AB  - A chronic diuretic abuse is common among healthy young women. An acute cessation
      of diuretic intake causes renal sodium retention with formation of edema due to
      diuretic-induced secondary hyperaldosteronism. Therefore, diuretics should be
      tappered over weeks or even months in these patients. Other clinical situations
      where therapy with diuretics is potentially deleterious are pregnancy and
      systemic sclerosis. In pregnant women, diuretic-induced acute or chronic
      depletion of the plasma volume can lead to placental hypoperfusion and
      preeclampsia. Patients with systemic sclerosis have very high levels of blood
      renin. Diuretic-induced volume depletion provides another stimulus of the renin
      angiotensin system and may cause a rapidly progressive renal failure requiring
      dialysis within days or weeks. The sclerodermal renal crisis is associated with a
      high early mortality. There is evidence that sclerodermal renal crisis can be
      avoided when patients are treated with an Angiotensin Converting Enzyme (ACE)
      inhibitor.

PMID- 10894029
TI  - [Place of definitive cardiac stimulation in cardiomyopathies and atrial
      arrhythmia].
AB  - Definitive cardiac stimulation ralatually used for brady cardia are going to be
      in the third millennium the specific therapy of arrhythmia and cardiomyopathy. In
      the last 10 years, may progress occur in the use of cardiac stimulation as
      hemodynamic therapy of obstructions hypertrophic and dilated cardiomyopathies
      resistant to conventional medical treatment. Moreover auricular stimulation
      present antiarrhythmic effects in some atrial arrhythmias as auricular
      fibrillations auricular diseases and atypical flutters. It confirmed by
      prospective multicentric randomized trials cardiac stimulation may represent in
      the future a good physiopathologic and efficient treatment free from the side
      effects of drugs that remain partially active. These perspectives needs to be
      modulated by the known and acceptable risks of a definitive cardiac stimulation.

PMID- 10894030
TI  - [Auricular fibrillation].
AB  - There is many progresses in term of comprehension of physiopathologic mechanisms
      and also therapeutic indications. The increase of treatment modalities need a
      clear strategy and an adapted choice from pharmacologic, to surgical, external
      electric shock, prophylactic cardiac stimulation, implantable auricular
      defibrillation, and ablative methods.

PMID- 10894031
TI  - [Hypertension emergencies].
AB  - Hypertensive emergencies include clinical situations with different prognosis.
      The emergencies are defined by the gravity of acute visceral failures. They need
      a parenteral treatment. Hypertensive emergency is less severe when blood pressure
      increase remain isolated and then is controlled progressively by oral treatment.
      The use of the calcium inhibitors by sublingual way is non controversies.
      Injectable nicardipine and uradipil represent an important progress in
      pharmacologic management of hypertensive emergencies.

PMID- 10894032
TI  - [Cardiogenic shock in the acute phase of myocardial infarction].
AB  - Cardiogenic shock (CC) is the most common cause of death in acute myocardial
      infarction (MI) and it has been often associated with fatal evolution. The aim of
      this study is to emphasize the positive impact of myocardial revascularisation
      especially percutaneous coronary angioplasty (PTCA) on short and mid term
      survival of 35 patients hospitalised for acute MI with CC. All the 11 patients
      who were on conventional therapy died, whereas the hospital mortality rate of the
      24 patients who underwent primary PTCA was 41%. PTCA in CC complicating MI is
      highly effective and reduces the mortality rate in the literature from 80% to
      40%. For this reason PTCA should be performed in each case of MI with CC seen in
      the first 6 hours.

PMID- 10894033
TI  - [Evolution after 5 years of percutaneous pulmonary valvulotomy: report of 47
      cases].
AB  - 47 patients aged from 2 to 59 years affected by valvular congenital or mixed
      pulmonary stenosis including three fallot trilogies and one patient with right
      congestive cardiac failure are treated by percutaneous pulmonary valvulotomy
      between october 1986 and december 1990. All patients have been controlled with a
      mean follow-up of 6.5 +/- 1.1 years. The total gradient rate between pulmonary
      artery and right ventricule decrease from 112 +/- 55 mm Hg to 20 +/- 8 mm Hg on
      the last control with disappearance of infundibular inflammation and inter
      auricular shunt in all the concerned cases. We observe the regression of right
      cardiac failure symptoms with disappearance of tricuspid insufficiency in the
      cases of advanced pulmonary stenosis with right ventricular dysfunction.
      Percutaneous pulmonary valvulotomy by its simplicity and harmlessness, its long
      term efficiency is a good method of treatment of pure valvular or mixed pulmonary
      stenosis.

PMID- 10894034
TI  - [Peripheral infected aneurysm: report of 15 cases].
AB  - In this retrospective study we report 15 cases of peripheral infected aneurysms.
      The sex ratio was 13/2 and the mean age was 23 years. Patients presented with
      infection syndrome in 9 cases, vascular mass in 11 cases and limb ischemia in 2
      instances. Arterial lesion was documented and confirmed by echography,
      tomodensitometry and angiography. The infection was recognised by different
      criteria the main one being micro-organism isolation. In 10 cases aneurysm was
      secondary to bacterial endocarditis, in 4 it was primary and in one case it was
      related to arterial catheter procedure. Treatment is based on antibiotics and
      surgical management by removing of infected aneurysm and arterial restoration
      whenever possible. Arterial flowerest re-establishment was done in 10 patients
      among whom 6 by anatomic procedures 4 by extra-anatomic ones. Hospital mortality
      rate was 13% (2/15), all deaths occurred after cardiac surgery for endocarditis.
      Two patients were readmitted for adjacent spine infection, one month and one and
      a half respectively after surgery. One young patient required late surgery (aorto
      bifemoral bypass) 24 months after initial treatment and one patient died by intra
      duodenal rupture of recurrent false aneurysm. Analysis of our results and
      literature review allow discussion of clinical, physiopathological and specially
      therapeutic aspects of infected aneurysm.

PMID- 10894035
TI  - [Percutaneous mitral commissurotomy: simplified new method].
AB  - We report a new simplified method of mitral dilatation done on 146 patients. This
      technique use the Inoue balloon with progressive diameters under ultrasonographic
      control, avoiding the arterial part of the dilatation. The population include 9
      pregnant women, 13 children, 13 with restenosis and closed heart and 12
      restenosis after dilatation. Mean age is 32 +/- 16 years (9 to 72) and sex ratio
      3.7 (114 F/32 M). Three groups are individualized according to histopathologic
      exam of mitral structure, group I (26%) concern good indication and III (32%) bad
      indication for this technique, group II (42%) contain intermediate indications.
      Commissurotomy increase the mean mitral square for 0.2 to 1.9 +/- 0.1 cm_. We
      observe 3 cases of chirurgical mitral insufficiency needing remplacement
      recruited for 2 patients from the group III. Mean fluoroscopic exposition time is
      5.2 +/- 3.3 mn and procedure duration 18 +/- 11 mn. Hospitalisation duration is
      one day for 95% of the patients. This method remaining simple, efficient and safe
      permit a gain in time of 70% with a good comfort for patient and a return to work
      on the 4th day.

PMID- 10894036
TI  - [Percutaneous implantation under local anesthesia of an implantable automatic
      defibrillator: report of the first Tunisian case].
AB  - We report the case of a 58 years old male affected by a severe relapsing
      ventricular tachycardia despite a well administered anti arrhythmic therapy.
      Etiology is an arrhythmogene right ventricular dysplasia. Considering the
      severity of this arrhythmia we proceed to percutaneous implantation of an
      automatically implantable defibrillator under local anesthesia. Evolution was
      favorable with a follow-up of 3 months.

PMID- 10894037
TI  - [Acute arterial ischemia due to tumor embolism after pulmonary resection: report
      of two cases and review of the literature].
AB  - From january 1984 to december 1999 we operate in our institution, 465 patients
      affected by lung cancer. In the early post-operative period we observe two
      arterial peripheral embolic events. Treatment consist in surgical embolectomy by
      Fogarty probe under femoral way. We don't observe post-operative complications or
      any functional sequelae. For the two patients tumoral character of the embolism
      was confirmed this work confirm the need of pre-operative precautions to avoid
      this complication that way be severe when in diagnosed or treated lately.

PMID- 10894038
TI  - [Infectious enterococcal endocarditis associated with Laubry and Pezzi syndrome].
AB  - Laubry and Pezzi syndrome is a rare but serious complication of ventricular
      septal defect that increase the infectious endocarditis risk. Authors report a
      case of an 18 years old young girl presenting an enterococcus infectious
      endocarditis associated to Laubry and Pezzi syndrome. Initial course is not
      favourable requiring a surgical treatment in the acute stage. Bacterial
      endocarditis combined with Laubry and Pezzi syndrome have a poor prognosis
      needing observation and strict preventive precautions when a favoring factor is
      present.

PMID- 10894039
TI  - [Contracted endocardial fibroelastosis in children: report of a case].
AB  - Endocardial fibroelastosis is un uncommon disease and it has a very bad prognosis
      since fatal evolution is usual before 2 years old. We report the case of a 20
      years old woman who is affected with the contracted form of this disease
      associated with atrial septal defect (ASD) and mitral regurgitation. This disease
      was discovered by endocardial biopsy when she was 4 years old and underwent
      surgical resection of endocardial fibrosis, a patch on the ASD and mitral valve
      replacement. She was rehospitalised 15 years later with heart failure although
      continuous digitoxin therapy.

PMID- 10894040
TI  - [The Amplatzer prosthesis: new therapeutic closure approach for interauricular
      communications].

PMID- 10894041
TI  - [Platelet alloantigens and their clinical implications. Part 2: Clinical
      implications].

PMID- 10894042
TI  - [Respiratory effects of outdoor pollution].

PMID- 10894043
TI  - [Premature rupture of fetal membranes. Its management is still disputed!].
AB  - The aim of this study is to have an idea about the epidemiologic and clinic
      profile of the PRM, the management of the PRM. We conclude from this
      retrospective study about 374 cases, that the PRM frequency is about 2.67%. It
      reaches particularly the young women, primipar (57.48%) and not happen of this
      accident. The diagnosis was clinical in general. In the doubtful cases, amniotic
      infection was present in 25.13%. The delivery was characterized by the
      complications were dominated by prematurity and neonatal infection which both
      caused a high perinatal mortality 49.3%). A better sanitary education of any
      pregnant woman, a regular follow-up of the pregnancies, a treatment of each
      etiologic factor of this accident, a good per and postnatal supervision could
      remarkably limit the incidence of this obstetrical accident and also improve the
      maternal and fetal prognosis.

PMID- 10894044
TI  - [Hepatitis C virus antibodies in 34130 blood donors in Tunisian Sahel].
AB  - Since January 6th 1994 to december 31 1997. We researched hepatitis C Virus
      antibodies by second and third generation ELISA in 34,130 bloods donors living in
      "Sahel Tunisien". 193 were positive (0.56%). Only 171 of them were secondary
      tested by immunoblot assay (anticore, anti NS5, anti NS3, anti NS4). Which was
      positive in 53 cases (30.9%); in determined (presence of only one antibody) in 78
      cases (45.6%) and negative, in 40 cases (23.3%). There was a significant relation
      between a ratio over than 2.5 in ELISA and immunoblot positivity. Immune response
      to different hepatitis virus antigens were heterogeneous with predominant in
      determined profile. (78/171 cases). Most of donors of the last profile had either
      anti NS5 (32/78) or anti NS3 (33/78) and we excluded them even through usually
      negative in P.C.R and associated with a very low risk of contamination.

PMID- 10894045
TI  - [The use of neuron specific enolase in the prognosis and followup of
      neuroblastoma in children. Results of a retrospective series of 21 patients].
AB  - OBJECTIVE: To report the results of seric neuron specific enolase in pediatric
      neuroblastoma. PATIENTS AND METHODS: Our retrospective study concerns 21 children
      treated in our institution from 1992 to 1998 for neuroblastoma. Seric NSE was
      determined by immunoenzymology technique at different stages of the disease and
      the treatment. RESULTS: Mean value for the 39 dosages of the whole patients was
      127.9 ng/ml with a sensitivity of 56%, five patients has presented normal values.
      Mean value for the 18 patients in stage IV was 132.38 ng/ml. We also observed in
      3 patients, an evolution of the seric NSE parallel to this of the disease under
      chemotherapy. CONCLUSION: NSE represents a moderate sensitive and specific tumor
      marker for pediatric neuroblastoma. However, it represents a good value in
      prognosis and follow-up after chemotherapy.

PMID- 10894046
TI  - [Intestinal parasitosis and environmental pollution: 1343 pediatric cases in Beni
      Mellal, Morocco].
AB  - This study was undertaken to determine the possible health risk associated with
      raw wastewater use in agricultural purposes, particularly, the transmission of
      parasite infections among children of five regions in Beni-Mellal, Morocco. In a
      randomly-selected sample of 1343 children, 740 of them were from five regions
      using raw wastewater for agriculture, and 603 were from 4 control regions that do
      not practice wastewater irrigation. One or more parasite infections were
      identified in 50.8% of the children living in the wastewater re-use regions and
      in 8.2% only of the others. The seven parasites identified were Entamoeba
      histolytica, Giardia intestinalis, Ascaris lumbricoides, Trichuris trichiura,
      Enterobius vermicularis, Hymenolepis nana, Taenia saginata, which infected 34.3%,
      5.1%, 20.5%, 0.4%, 5.2%, 7.2%, 0.5% in the exposed population and 4.3%, 0.3%,
      3.8%, 0.3%, 1.0%, 0.6% and 0.0% in the control population respectively. In
      conclusion, raw wastewater use in Beni-Mellal lead to a high risk of parasite
      infections. Adequate treatment of wastewater is highly recommended.

PMID- 10894047
TI  - [Acute lymphoblastic leukemia in adults. Apropos of 42 cases].
AB  - Between 1989 and 1995, 42 cases with acute lymphoblastic leukemia (18 males and
      24 females) were diagnosed in our institution. Median age was 38.5 years (range,
      16-88 years). Leukocyte count was more than 30.10(9)/l in 54% of cases. According
      to the French-American-British (FAB) criteria, 67% were classified L1 and 33% L2.
      Sixteen patients were treated with 12LA80 protocol, 14 patients with LALA 85
      protocol, 6 patients with LALA 87 protocol and 6 patients with EORTC protocol.
      Complete remission was achieved in 22 cases (52%), 8 cases (20%) failed to
      respond and 12 (28%) died during induction. Relapse was observed in 10 cases. The
      4-year survival rate was 28% confirming the worse prognosis of this leukemia when
      treated with standard chemotherapy.

PMID- 10894048
TI  - [Lethal uropathies: prenatal diagnosis and feto-pathologic aspects].
AB  - Forty-three prenatal diagnoses of lethal urinary tract abnormalities were carried
      out during a five-year-period. The abnormalities were bilateral renal agenesis
      (56%), autosomal recessive polycystic kidney disease (16%), autosomal dominant
      polycystic kidney disease (14%), MECKEL-GRUBER syndrome and Prune-Belly syndrome
      (4%). The pregnancy was interrupted in thirty-five cases (81.4%).

PMID- 10894049
TI  - [Prolonged pregnancy: apropos of a series of 102 cases].
AB  - It was a retrospective and continuous prospective study about 102 post-term
      pregnancy recensed on a 14 months period. The aim of this study is to evaluate
      our management of post term pregnancy and the peto-maternal morbidity and
      mortality. RESULTS: Frequency of post-term pregnancy in our study is 5.92%, in
      rate of session sector is not higher it is of 18.62. There is no maternal
      mortality. Neonatal mortality is a about 19/1000, the rate of neonatal morbidity
      is 2.9%.

PMID- 10894050
TI  - [The effect of age and dehydration on the activity of the vasopressinergic system
      in rats].
AB  - The aim of our work was to study the different blood parameters as well as the
      activity of the vasopressinergic axis in young and mature male rats under normal
      conditions and following a 3-day dehydration cycle by water deprivation. Under
      normal conditions, our study demonstrates higher levels of vasopressin in mature
      rats as compared to young rats. This could be due in part to the higher blood
      osmolality in the mature rats. After dehydration, hypovolemia, plasmatic
      hyperosmolality, hypernatremia and hyperproteinemia cause a stimulation in
      vasopressin synthesis and release, as seen in results obtained from the
      hypothalamus, hypophysis and plasma in both young and mature rats. However, the
      response of the vasopressinergic axis to dehydration is greater in young rats,
      suggesting a more pronounced sensitivity to osmotic factors.

PMID- 10894051
TI  - [The Dalkon Shield, a forgotten device, responsible for actinomycosis].
AB  - The authors report a case of a Dalkon Shield, forgot in a 55 years old patient,
      responsible for actinomycosis infection. Basing on a review of the literature,
      diagnostic methods and management of this kind of complication are discussed.

PMID- 10894052
TI  - [An unusual bronchial foreign body: an hydatid cyst membrane].
AB  - Long course bronchopneumonia in child imposes a bronchoscopy to research a
      foreign body. We report the case of a 4 years old child presenting an unusual
      foreign body overdraft at rigid tube bronchoscopy indicated for a training
      pneumonia. It was the membrane of burst pulmonary hydatic cyst obturing left
      bronchial tree. His total extraction permitted the complete recovery without
      retention of the membrane.

PMID- 10894053
TI  - [Anesthesia and resuscitation in Arabo-Islamic medicine: analytic study through
      Ibn Sina].
AB  - Nervous system anatomy knowledge acquired by arabo-islamic physicians enabled
      them to know its physiology represented by its excitability and its
      conductibility, and to understand pain physiology. Ibn Sina in his book entitle
      "The Canon of Medicine" precise anesthetic drugs and their side effects. Among
      these anesthetic means there were opium and ice. Ibn Sina distinguished organic
      pain and psychogenic pain. He used sedative and antalgic and soporific drugs in
      treatment of some psychologic diseases as melancholia. Moslem physicians were the
      first to use cold water to treat superficial burns. Anesthesia which lead to
      heavy sleep to used achieve surgical operations by oral, nasal(inhalation) and
      rectal route as it was described by Ibn Sina who indicated dosage to achieve
      three or four hour anesthesia which was necessary in an amputation surgery.

PMID- 10894058
TI  - Research and the survival of radiology in academic institutions.

PMID- 10894059
TI  - Pitfalls in myocardial perfusion assessment with dynamic MR imaging after
      administration of a contrast material bolus in dogs.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the artifacts observed on
      myocardial perfusion curves derived from an inversion-prepared fast gradient-echo
      (GRE) imaging sequence in dogs after injection of a gadolinium-based contrast
      agent. MATERIALS AND METHODS: Six mongrel dogs were divided into three groups. In
      groups 1 and 2, anesthesia was maintained with pentobarbital. Group 2 also
      received an intravenous injection of atropine (0.03 mg/kg). In group 3,
      anesthesia was maintained with isoflurane (1.0%). Imaging was performed on a 1.5
      T magnetic resonance (MR) imaging unit (one section per heart beat, a 30 x 15-cm
      field of view, 10-mm section thickness, and 64-kHz bandwidth). Region-of-interest
      (ROI) markers were placed on the blood pool of the left intraventricular cavity,
      anterior wall of the left ventricle, and anterior to the chest wall to track
      respiratory motion. RESULTS: In group 1, the signal intensity (SI) periodically
      increased during each inspiration due to respiratory sinus arrhythmia. The
      relation between the SI increase and the variation of the delay between images
      was demonstrated in vitro and by computer simulations. No periodic increase of
      the SI was observed when regular cardiac rhythm was maintained by pharmacologic
      inhibition of the vagal-mediated chronotropic response with either the addition
      of atropine to pentobarbital or the use of isoflurane as the anesthetic agent.
      CONCLUSION: In an inversion-prepared fast GRE sequence, respiratory sinus
      arrhythmia can induce periodic SI increase by varying the respiratory rate
      interval and delay between images.

PMID- 10894060
TI  - View box luminance measurements and their effect on reader performance.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to investigate the
      importance of view box luminance and viewing conditions on low-contrast detection
      by readers. MATERIALS AND METHODS: Radiographs of a mammographic contrast-detail
      phantom were examined on 632 view box panels. The luminance of these panels was
      obtained by using a calibrated meter and ranged from 860 to 3,300 nit. Twelve
      radiologists reported the number of contrast-detail disks for each size
      (diameter, 0.3-7.0 mm) deemed to be visible on films with optical densities of
      1.00-2.60. Radiologist performance in reading low-contrast phantom images was
      also studied as a function of room illuminance and image masking. RESULTS: Median
      luminance was 1,700 nit, with 25- and 75-percentile values of 1,450 and 2,150
      nit, respectively. Low-contrast visibility generally was independent of view box
      luminance, regardless of film density or disk diameter. Low-contrast visibility
      deteriorated when masking around the image was removed and at normal room
      illuminance. The greatest deterioration in performance occurred at the highest
      film densities and with the smallest size disks. CONCLUSION: Detection of low
      contrast features on radiographs is relatively independent of view box luminance,
      but it is degraded by the presence of stray light and by increased room
      illuminance.

PMID- 10894061
TI  - In vivo flow-independent T2 measurements of superior mesenteric vein blood in
      diagnosis of chronic mesenteric ischemia: a preliminary evaluation.
AB  - RATIONALE AND OBJECTIVES: The authors attempted to determine whether the T2
      relaxation time of superior mesenteric vein (SMV) blood would decrease in
      patients with chronic mesenteric ischemia after a meal. MATERIALS AND METHODS:
      Thirty-two patients without chronic mesenteric ischemia and eight patients with
      symptomatic chronic mesenteric ischemia underwent magnetic resonance (MR)
      imaging. All examinations were performed with a 1.5-T unit, a modified Carr
      Purcell-Meiboom-Gill sequence, final section-selective pulse of 180 degrees, and
      spiral readout gradients. Measurements of SMV blood T2 were obtained after at
      least 6 hours of fasting and 15 and 35 minutes after ingestion of 240 mL of a
      liquid nutritional supplement. Maximal change of the SMV blood T2 was expressed
      as a percentage of the fasting T2 in all patients. RESULTS: In control patients,
      SMV blood T2 increased postprandially by 9.4% +/- 1.3 (95% confidence level;
      range, 6.8%-11.9%) (data range, -7.3% to 25.6%) compared with fasting T2. In
      symptomatic patients, SMV blood T2 decreased postprandially by 15.8% +/- 2.2 (95%
      confidence level; range, -20.1% to -10.7%) (data range, -7.9% to -25.3%). The
      difference between the two groups was statistically significant (P < .0001 by
      Student unpaired t test). CONCLUSION: Measurement of SMV blood T2 is a promising
      test for chronic mesenteric ischemia diagnosis. Therefore, conversion of T2
      measurements to estimate oxygen saturation may not be necessary for all cases of
      this clinical indication.

PMID- 10894062
TI  - Call obligations in radiology residency: a survey.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the initial assignment of call
      responsibilities during residency, the effect on call obligations of the number
      of residents, and the differences between private and university programs and
      level 1 and non-level 1 trauma centers. MATERIALS AND METHODS: A survey was sent
      to all 203 diagnostic radiology residency programs accredited by the
      Accreditation Council for Graduate Medical Education. Chief residents at 21
      institutions were surveyed by phone or in person. Directors of residency programs
      in the Graduate Medical Education Directory received the survey electronically.
      RESULTS: Responses were received from 99 (68 university, 31 private practice) of
      the 203 programs. Nine (9%) reported both a decreased number of residents and a
      subsequent increase in call obligations. First-year residents generally began to
      accept calls with a senior resident or alone at a median of 6 months, although 15
      (48%) private practice programs required them to accept calls alone before this
      time. First-year residents at university programs (31%) were more likely to
      assume call duties during the first 6 months accompanied by a senior resident.
      Maximum time before 1st-year residents started going on call was 13 months.
      CONCLUSION: Call obligations remain a resident responsibility. University and
      private practice programs differ more than level 1 and non-level 1 trauma
      centers.

PMID- 10894063
TI  - Registration of 3D cerebral vessels with 2D digital angiograms: clinical
      evaluation.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the accuracy
      and speed of a new, semiautomatic method of three-dimensional (3D)-two
      dimensional (2D) vascular registration. This method should help guide
      endovascular procedures by allowing interpretation of each digital subtraction
      angiographic (DSA) image in terms of precreated, 3D vessel trees that contain
      "parent-child" connectivity information. MATERIALS AND METHODS: Connected, 3D
      vessel trees were created from segmented magnetic resonance (MR) angiograms.
      Eleven total DSA images were registered with such trees by using both our method
      and the current standard (manual registration). The accuracy of each method was
      compared by using repeated-measures analysis of variance with correction for
      heterogeneity of variance to evaluate separation of curve pairs on the view
      plane. Subjective clinical comparisons of the two registration methods were
      evaluated with the sign test. Registration times were evaluated for both methods
      and also as a function of the error in the initial estimate of MR angiographic
      position. RESULTS: The new registration method produced results that were
      numerically superior to those of manual registration (P < .001) and was
      subjectively judged to be as good as or better by clinical reviewers.
      Registration time with the new method was faster (P < .001). If the rotational
      error in the initial estimate of MR angiographic position is less than 10 degrees
      around each axis, the registration itself took only 1-2 minutes. CONCLUSION: This
      method is quicker than and produces results as good as or better than those of
      manual registration. This method should be able to calculate an initial
      registration matrix during endovascular embolization and adjust that matrix
      intermittently with registration updates provided by automatic tracking systems.

PMID- 10894064
TI  - Alternative educational pathways: their future role in changing the mental models
      of academic radiology.

PMID- 10894065
TI  - Radiologic sciences research in the next century: new national initiatives and
      evolving university and industrial relationships.

PMID- 10894066
TI  - Evaluating online radiology information resources.

PMID- 10894067
TI  - Efficiency in education.

PMID- 10894068
TI  - Occurrence of adverse reactions to gadolinium-based contrast material and
      management of patients at increased risk: a survey of the American Society of
      Neuroradiology Fellowship Directors.
AB  - RATIONALE AND OBJECTIVES: The authors attempted to determine the frequency and
      severity of adverse reactions to gadolinium-based magnetic resonance (MR)
      contrast agents and to identify strategies for management of patients at
      increased risk. MATERIALS AND METHODS: American Society of Neuroradiology program
      directors were surveyed about adverse reactions at their institutions to
      gadolinium-based contrast agents, the contrast agents responsible, and the
      management of patients with allergy-like reactions to iodinated or gadolinium
      based agents who required MR contrast agent administration. RESULTS: Fifty-three
      (50.5%) surveys were received from 105 centers. Of 687,255 gadopentetate
      dimeglumine injections, 314 (0.046%) nonallergic reactions and 107 (0.016%) mild,
      28 (0.004%) moderate, and five (0.001%) severe allergy-like reactions occurred.
      Of 74,275 gadodiamide injections, 11 (0.015%) nonallergic and 12 (0.016%) mild
      allergy-like reactions occurred. Of 64,005 gadoteridol administrations, 171
      (0.267%) nonallergic reactions and 49 (0.077%) mild, 29 (0.047%) moderate, and 11
      (0.017%) severe allergy-like reactions occurred. Twenty-six departments took no
      precautions for patients with previous allergy-like reactions to iodinated
      contrast material. Nineteen did not premedicate patients who previously had
      reactions to gadolinium-based agents before repeat administration of MR contrast
      agents. CONCLUSION: Although MR contrast agents are safe, adverse reactions
      occur. Many centers have not adopted policies for the OFF

PMID- 10894069
TI  - Computerized analysis of lesions in US images of the breast.
AB  - RATIONALE AND OBJECTIVES: Breast sonography is not routinely used to distinguish
      benign from malignant solid masses because of considerable overlap in their
      sonographic appearances. The purpose of this study was to investigate the
      computerized analyses of breast lesions in ultrasonographic (US) images in order
      to ultimately aid in the task of discriminating between malignant and benign
      lesions. MATERIALS AND METHODS: Features related to lesion margin, shape,
      homogeneity (texture), and posterior acoustic attenuation pattern in US images of
      the breast were extracted and calculated. The study database contained 184
      digitized US images from 58 patients with 78 lesions. Benign lesions were
      confirmed at biopsy or cyst aspiration or with image interpretation alone;
      malignant lesions were confirmed at biopsy. Performance of the various individual
      features and output from linear discriminant analysis in distinguishing benign
      from malignant lesions was studied by using receiver operating characteristic
      (ROC) analysis. RESULTS: At ROC analysis, the feature characterizing the margin
      yielded Az values (area under the ROC curve) of 0.85 and 0.75 in distinguishing
      between benign and malignant lesions for the entire database and for an
      "equivocal" database, respectively. The equivocal database contained lesions that
      had been proved to be benign or malignant at cyst aspiration or biopsy. Linear
      discriminant analysis round-robin runs yielded Az values of 0.94 and 0.87 in
      distinguishing benign from malignant lesions for the entire database and for the
      equivocal database, respectively. CONCLUSION: Computerized analysis of US images
      has the potential to increase the specificity of breast sonography.

PMID- 10894070
TI  - MR imaging of the temporomandibular joint: a validation experiment in vitro.
AB  - RATIONALE AND OBJECTIVES: The authors compared magnetic resonance (MR) image
      quality obtained from 3- and 1-mm-thick sections in the depiction of the
      temporomandibular joint (TMJ) and its adjacent structures. MATERIALS AND METHODS:
      Eight TMJ specimens from four adult cadaver heads were depicted with MR imaging.
      Both 3- and 1-mm-thick sections were generated. One oral and maxillofacial
      radiologist, who was blinded to section thickness, evaluated the anatomic details
      of the images. Subsequently, the joints were surgically explored by two oral and
      maxillofacial surgeons, and the physical findings were recorded. RESULTS: Some
      statistically significant differences were found between the physical findings
      and the 3-mm-thick section images, while no significant differences were found
      with the 1-mm-thick sections. CONCLUSION: The TMJ and its adjacent structures
      were better depicted by thinner MR images.

PMID- 10894071
TI  - Hepatic lesion ablation with bipolar saline-enhanced radiofrequency in the
      audible spectrum.
AB  - RATIONALE AND OBJECTIVES: The authors' purpose was to create larger and more
      regular liver lesions in vitro by testing a new hyperthermia approach that uses a
      bipolar saline-enhanced electrode for radiofrequency (RF) in the audible spectrum
      and a greater power supply. MATERIALS AND METHODS: The authors' hyperthermia
      approach (group A, n = 23) was used in excised porcine livers, and the results
      were compared with those of a previously described monopolar saline-enhanced
      electrode procedure (group B, n = 23). In each set of experiments, RF in the
      audible spectrum current (50 Hz) was provided for 15 minutes with a similar
      ablation protocol. Electrical variables (impedance, current, voltage, power, and
      energy), temperatures in the lesions, volume size, regularity ratio of the
      lesion, and microscopic findings were measured. RESULTS: In group A, the mean
      volume size and the mean regularity ratio values were 144.8 cm3 +/- 59.8 and 0.78
      +/- 0.1, respectively. In group B, the mean volume size and regularity ratio
      values were 62.1 cm3 +/- 36.4 and 0.62 +/- 0.1, respectively. The values in group
      B were thus significantly lower than those in group A (P < .01). The lesions in
      group A were also more homogeneous. No significant differences were found in
      electrical variables. CONCLUSION: The new bipolar saline-enhanced electrode
      produced larger, more regular, and more homogeneous lesions ex vivo than the
      previously used monopolar saline-enhanced electrode method. Using a greater power
      supply increased the amount of coagulative necrosis.

PMID- 10894072
TI  - Personnel exposure rates during simulated biopsies with a real-time CT scanner.
AB  - RATIONALE AND OBJECTIVES: Real-time computed tomography (CT) has the potential to
      expedite and improve CT-guided needle biopsies by allowing cross-sectional images
      to be viewed in real time as a needle is advanced toward the target lesion. A
      major concern about this procedure is the scattered and leaked radiation to which
      the operator is exposed. This study was undertaken to determine the exposure
      rates around a CT scanner during CT-guided needle biopsies and to identify the
      areas of greatest personnel exposure. MATERIALS AND METHODS: Pig and human
      cadavers were used to simulate patients undergoing a CT-guided needle biopsy.
      Various anatomic biopsy sites were used. The radiologist's exposure was assessed
      by timing the procedure and measuring the exposure rates around the CT scanner
      with an ionization-chamber survey meter. Ion-chamber measurements multiplied by
      the time the radiologist spent performing several mock biopsies were compared
      with film dosimeter results. Doses to the hands, wrists, and whole body were
      measured with ring, wrist, body, and collar film dosimeters. RESULTS: The average
      time required to perform a single biopsy was about 1 minute. The dose to the
      radiologist performing the simulated biopsies was calculated to be 123 mR, 68 mR,
      14 mR, and less than 0.5 mR to the fingers, wrist, collar, and body,
      respectively, as calculated from ionization-chamber and time measurements. These
      exposure rates correlate well with the film dosimeter readings accumulated during
      the mock procedures. CONCLUSION: The dose received by the radiologist performing
      a CT-guided biopsy was comparable to that of other interventional procedures. In
      addition, operating from the head of the machine (ie, distal to the bed) appeared
      to markedly reduce personnel exposure, due to the shielding in the gantry of the
      CT scanner used in the study.

PMID- 10894073
TI  - Medical students and radiology residents: can they learn as effectively with the
      same educational materials?
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the
      effectiveness of resident-prepared, independent-learning materials for teaching
      chest radiology to medical students. MATERIALS AND METHODS: Students from three
      U.S. medical schools enrolled in radiology clerkships between March 1998 and June
      1998 were randomly divided into control (n = 27) and experimental (n = 31)
      groups. The experimental group studied 12 chest radiology independent-learning
      cases (intervention) used to teach radiology residents in a previous study. Both
      groups took a 36-item, multiple-choice test (previously used to test radiology
      residents) on three occasions (before intervention [pretest], 1 day after
      intervention [posttest], and 2-4 weeks after intervention [final examination]).
      Student scores were then compared with resident scores. RESULTS: Mean scores were
      similar across institutions at pretest, but increases at posttest and final
      examination scores differed across time, school, and group (P < .005). Mean
      differences in scores between experimental and control groups at pretest,
      posttest, and 2-4-week final examination were -0.22, 9.79, and 9.14,
      respectively, demonstrating increased performance at posttesting that remained
      present (though slightly attenuated) 2-4 weeks later. Comparing performance,
      residents had mean pretest scores of 19.2 and students of 14.1, a five-point
      difference attributable to the residents' greater experience. Both residents and
      students gained approximately nine points at posttest. At final examination, the
      difference between residents and students was only 1.4 points, suggesting the
      experimental program (teaching materials) brought students close to the long-term
      retention shown by residents. CONCLUSION: Independent study of resident-prepared
      chest radiology teaching cases increased medical student knowledge for at least 2
      or 4 weeks after instruction. Although starting at lower knowledge levels,
      students experienced gains in knowledge comparable to those of residents,
      suggesting the same materials can be used to teach both students and residents.

PMID- 10894074
TI  - Recent advances in cancer chemotherapy.

PMID- 10894075
TI  - Results of and comments on the 1998 survey of the American Association of
      Academic Chief Residents in Radiology.
AB  - RATIONALE AND OBJECTIVES: The American Association of Academic Chief Residents in
      Radiology annually surveys residency programs on a variety of issues related to
      residency training. The survey allows for comparison between programs regarding
      training and follows trends on current issues. MATERIALS AND METHODS:
      Questionnaires were mailed to all accredited programs in the United States (188
      programs). The questionnaire consisted of questions regarding general demographic
      information and specific topics regarding residency training. The 1998 survey
      focused on turf issues, teleradiology use, residency selection, and prior
      training. RESULTS: Completed surveys from 61 programs (32.4%) were returned.
      Important findings included (a) the ongoing turf battles regarding vascular and
      obstetric-gynecologic ultrasound, both in general hospital and emergency
      department patients, (b) the use of teleradiology by most residents, and (c) the
      low percentage of women in radiology residency programs. CONCLUSION: The
      information obtained during yearly surveys is useful for program evaluation and
      future planning. Current survey results indicate an increasing use of
      teleradiology in residency over the past 4 years. The turf battles in
      ultrasonography (both vascular and obstetric) have remained unchanged over the
      same time frame.

PMID- 10894076
TI  - Networking 101: a brief course on the basics.

PMID- 10894077
TI  - Signal intensity changes in anterior cruciate ligament autografts: relation to
      magnetic field orientation.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to use magnetic resonance
      (MR) imaging to investigate the contribution of graft alignment to changes in
      signal intensity in anterior cruciate ligament (ACL) autografts. MATERIALS AND
      METHODS: Forty patients who had undergone reconstruction of the ACL with an
      autograft underwent MR examinations of the knee in extension and flexion. The
      signal intensity of the intratibial bone tunnel and intraarticular portions of
      ACL graft were measured, and signal intensity ratios were defined by dividing the
      mean signal intensity of the graft by the mean signal intensity of the fatty
      marrow. The angles from the intraarticular and intratibial bone tunnel portions
      of the graft to the static magnetic field were measured for each signal intensity
      ratio. The Hotteling T2 test was used to evaluate the differences in signal
      intensity ratios to the differences in angles from flexion to extension for the
      intratibial bone tunnel and intraarticular portions of the graft. RESULTS:
      Significant increases occurred in the signal intensity of the graft and the angle
      with the change in position from flexion to extension for both the intratibial
      bone tunnel (P < .01) and intraarticular (P < .01) portions of the graft. Changes
      in signal intensity ratios were greater than zero, and these values differed
      significantly for the intraarticular and the intratibial bone tunnel (P < .01)
      portions of the graft. CONCLUSION: The signal intensity changes of the ACL graft
      related to changes in its alignment are likely a result of the magic-angle
      effect.

PMID- 10894078
TI  - Non-small-cell lung cancer: practice patterns of extrathoracic imaging.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to identify practice
      patterns of extrathoracic imaging in patients newly diagnosed with non-small-cell
      lung, cancer. MATERIALS AND METHODS: The authors retrospectively reviewed the
      charts of 125 patients (71 men, 54 women; mean age, 67 years) from five hospitals
      (25 patients each) with newly diagnosed non-small-cell lung cancer. Charts were
      reviewed for cancer cell type, evidence of metastatic disease, and performance
      and results of extrathoracic imaging, including computed tomography (CT) and
      magnetic resonance (MR) imaging of the brain, bone scanning, and abdominal CT.
      RESULTS: Of 125 patients, 77 (62%) underwent extrathoracic imaging. These
      patients included 64 (64%) of 100 patients with clinical symptoms or laboratory
      signs of metastatic disease and 13 (52%) of 25 patients with no such indications.
      Extrathoracic imaging did not differ according to cancer cell type: It was
      performed for 30 (60%) of 50 patients with squamous cell carcinoma, 26 (60%) of
      43 patients with adenocarcinoma, and 16 (73%) of 22 patients with non-small-cell
      lung cancer that was not further characterized. Brain CT or MR imaging bone
      scanning, or abdominal CT were performed in only 48%, 39%, and 30% of patients,
      respectively. Brain CT or MR images or bone scans revealed metastatic disease in
      seven of 20 and nine of 22 patients with clinical symptoms or laboratory signs of
      disease, respectively. These examinations revealed disease in four of 40 and two
      of 27 patients without such symptoms or signs, respectively (P < .05). No
      significant differences emerged among the practice patterns at the five
      participating hospitals. CONCLUSION: No consensus was found on performance of
      extrathoracic imaging in patients with newly diagnosed non-small-cell lung
      cancer.

PMID- 10894079
TI  - A sequential chart for the audit-based evaluation of screening mammogram
      interpretation.
AB  - RATIONALE AND OBJECTIVES: Auditing has received much attention recently as a
      method for radiologists to use to evaluate their interpretation of screening
      mammograms. U.S. Food and Drug Administration regulations require that some sort
      of audit be in place before a mammography screening facility can receive
      accreditation. Auditing presents a unique opportunity to monitor accuracy
      continually and identify problems early. Audit data present unique challenges,
      however, and appropriate methods must be used to control the risk of errors.
      MATERIALS AND METHODS: This article introduces a simple method for the task of
      deciding if a radiologist yields an acceptable positive predictive value based on
      audit. The method is based on "sequential" decision-making techniques that have
      found wide application in quality control problems. These techniques are
      developed for diagnostic radiology and embodied in an easy-to-use decision-making
      chart. RESULTS: Several examples, based on audit data from actual mammography
      facilities, provide insights into the use of these charts and the influence of
      (a) the selection of standards, (b) the selection of error risks, and (c)
      radiologist variability. The examples also serve to demonstrate another important
      property of this method--that is, it specifies the minimum amount of data that
      has to be collected before any decision can reliably be made. CONCLUSION: The
      chart presented in this article provides a method by which audit data can be used
      objectively to evaluate the accuracy of screening mammogram interpretation. The
      method controls the risk of either falsely accepting an unqualified radiologist
      or falsely rejecting a qualified radiologist. It should be a useful tool to
      radiologists who must evaluate their own practices.

PMID- 10894081
TI  - Limitations of student evaluations of curriculum.
AB  - RATIONALE AND OBJECTIVES: Medical student surveys are used extensively in the
      development and modification of curriculum. The purpose of this study was to look
      at medical student surveys of a radiology lecture series, evaluating the accuracy
      of student perceptions of learning and factors affecting them. MATERIALS AND
      METHODS: After a "Case of the Week" lecture series, 156 3rd-year medical students
      returned a survey evaluating the experience with 10 questions on a four-point
      scale (1 = disagree, 4 = agree very much) and took a clinical competency
      assessment (CCA) examination with a radiology substation. Survey responses were
      compared with actual examination performance, analyzed for how overall learning
      was characterized in specific educational objectives, and evaluated for factors
      affecting perceived learning. RESULTS: The mean response for perceived CCA
      examination preparedness was 1.83. The mean radiology station test score was
      90.43%. Correlations between student perception of learning and the scoring of
      focused learning objectives ranged from 0.33 to 0.48 (P < .01). Students
      responding 1 to items assessing perceived lecture organization, stimulation to
      read, and interest in the field of radiology had mean scores for perception of
      overall learning of 2.09-2.44 and mean scores for recommendation of course
      continuation of 1.68-2.46. Students responding 4 had means of 3.25-3.81 and 3.06
      4.0, respectively. CONCLUSION: Student perceptions of the value of curriculum
      were inaccurate compared with external measures of performance, and students
      poorly related their general impressions to specific learning objectives.
      Perceived lecture organization, stimulation to read, and interest in radiology as
      a specialty affected perceived overall learning and perceived value of the
      lecture series.

PMID- 10894080
TI  - CT detection of serious internal and skeletal injuries in patients with pelvic
      fractures.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine the
      percentage of patients with known pelvic fractures who have additional findings
      of intraabdominal injury, as diagnosed at abdominal computed tomography (CT), and
      to determine if patients with specific types or patterns of fractures are more
      likely to have additional injuries. MATERIALS AND METHODS: The authors reviewed
      the medical records of 200 consecutive patients (125 women, 75 men; age range, 4
      86 years) who had been admitted to a level 1 trauma center with osseous pelvic
      injury secondary to blunt trauma and who had undergone abdominal CT examinations.
      Abdominal CT findings in these patients were classified as negative, positive, or
      minimal and correlated with mechanism of pelvic fracture. RESULTS: Sixty-five
      (32%) of the 200 patients had negative CT findings, 43 (22%) had findings
      attributable to the trauma but required no follow-up, and 92 (46%) had positive
      findings that required nonsurgical management or exploratory laparotomy.
      Additional pelvic fractures were identified in 63 (32%) patients. The highest
      prevalence of additional injuries was in patients with Malgaigne fractures (four
      of 15, 27%) or bilateral pubic rami fractures (six of 18, 33%). CONCLUSION: CT
      examinations revealed that 135 (68%) of 200 patients with pelvic fractures
      secondary to blunt trauma had concomitant internal or skeletal injuries and that
      92 (46%) patients had injuries severe enough to require nonsurgical management or
      exploratory laparotomy. Patients with bilateral pubic rami fractures or Malgaigne
      fractures were particularly prone to additional injuries; therefore, abdominal CT
      examinations are recommended in these patients.

PMID- 10894082
TI  - The radiology case conference: preparation, presentation, and participation.

PMID- 10894083
TI  - Imaging neurologic complications of pregnancy and the puerperium.

PMID- 10894084
TI  - Recent advances in structure, binding sites with ligands and pharmacological
      function of beta-adrenoceptors obtained by molecular biology and molecular
      modeling.
AB  - The structure, binding sites interacting with ligands and the physiological
      functions of G-protein coupled beta-adrenoceptors (beta-ARs) are being elucidated
      by molecular biology and molecular modeling studies. The definition given amino
      acid sequences of beta-ARs in molecular biology and the analysis of three
      dimensional and functional binding sites interacting with ligands by molecular
      modeling may be important for identifying other functional beta-ARs in various
      tissues and discovering new drugs. Thus, this review focuses on the interaction
      sites for receptor-ligand and roles of functional beta-ARs as studied by
      molecular biology and molecular modeling.

PMID- 10894085
TI  - The specificity of platelet glutamate receptor supersensitivity in psychotic
      disorders.
AB  - Hypoglutamatergic function is implicated in the pathogenesis of schizophrenia,
      and supersensitivity of platelet NMDA receptors has been reported in
      schizophrenia. The aim of this study was to examine the platelet glutamate
      receptor sensitivity in patients with schizophrenia (n=12), mania with psychotic
      features (n=10) and depression with psychotic features (n=10) and matched
      controls (n=12) in order to assess if this is a marker of schizophrenia or occurs
      in other psychotic conditions. Glutamate receptor sensitivity was assessed using
      the intracellular calcium response to glutamate measured with spectrofluorometry.
      The percentage response of the schizophrenic and depressed psychotic subjects to
      glutamate stimulation was significantly greater than control subjects (p<0.005).
      The mania with psychotic features group was not significantly different to
      controls. This data suggests that platelet glutamate receptors may be
      supersensitive in schizophrenia and depression with psychotic features.
      Furthermore, the platelet may be a possible peripheral marker of glutamate
      function in schizophrenia and depression with psychotic features.

PMID- 10894086
TI  - Thiocyanate mediated antifungal and antibacterial property of goat milk
      lactoperoxidase.
AB  - Goat milk lactoperoxidase was purified using CM-Sephadex-C-50 ion exchange
      chromatography and Sephadex G-100 gel filtration. The purified protein was found
      to have high antifungal and antibacterial activity in a thiocyanate-H2O2 medium.
      The results are relevant enough to suggest the exploitation of LP-thiocyanate
      H2O2 system as an effective agent against many of the disease causing organisms
      in plants and animals.

PMID- 10894087
TI  - Cellular mechanisms involved in iso-osmotic high K+ solutions-induced contraction
      of the estrogen-primed rat myometrium.
AB  - The aim of the present study was to investigate the mechanisms involved in the
      contraction evoked by iso-osmotic high K+ solutions in the estrogen-primed rat
      uterus. In Ca2+-containing solution, iso-osmotic addition of KCl (30, 60 or 90 mM
      K+) induced a rapid, phasic contraction followed by a prolonged sustained plateau
      (tonic component) of smaller amplitude. The KCl (60 mM)-induced contraction was
      unaffected by tetrodotoxin (3 microM), omega-conotoxin MVIIC (1 microM), GF
      109203X (1 microM) or calphostin C (3 microM) but was markedly reduced by tissue
      treatment with neomycin (1 mM), mepacrine (10 microM) or U-73122 (10 microM).
      Nifedipine (0.01-0.1 microM) was significantly more effective as an inhibitor of
      the tonic component than of the phasic component. After 60 min incubation in Ca2+
      free solution containing 3 mM EGTA, iso-osmotic KCl did not cause any increase in
      tension but potentiated contractions evoked by oxytocin (1 microM), sodium
      orthovanadate (160 micrM) or okadaic acid (20 microM) in these experimental
      conditions. In freshly dispersed myometrial cells maintained in Ca2+-containing
      solution and loaded with indo 1, iso-osmotic KCl (60 mM) caused a biphasic
      increase in the intracellular Ca2+ concentration ([Ca2+]i). In cells superfused
      for 60 min in Ca2+-free solution containing EGTA (1 mM), KCl did not increase
      [Ca2+]i. In Ca2+-containing solution, KCl (60 mM) produced a 76.0 +/- 16.2%
      increase in total [3H]inositol phosphates above basal levels and increased the
      intracellular levels of free arachidonic acid. These results suggest that, in the
      estrogen-primed rat uterus, iso-osmotic high K+ solutions, in addition to their
      well known effect on Ca2+ influx, activate other cellular processes leading to an
      increase in the Ca2+ sensitivity of the contractile machinery by a mechanism
      independent of extracellular Ca2+.

PMID- 10894088
TI  - Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission
      tomography.
AB  - Using positron emission tomography (PET) and [11C]N-methylspiperone (NMSP), we
      examined 5-HT2 receptors in the cortex of schizophrenic patients in whom we
      previously observed decreased prefrontal D1 receptor binding. The subjects were
      10 neuroleptic-naive schizophrenic patients, 7 schizophrenic patients who were
      drug-free but had previously been treated with neuroleptics, and 12 normal
      controls. A non-significant trend towards decreased prefrontal [11C]NMSP binding
      was observed in the neuroleptic-treated patients, suggesting a possible effect of
      previous neuroleptic treatment on the alteration in cortical 5-HT2 function.
      However, the neuroleptic-naive patients showed no noticeable difference in
      cortical [11C]NMSP binding compared to controls. Our results do not rule out the
      role of 5-HT2 function as a crucial site of therapeutic activity of
      schizophrenia, but they do suggest that cortical 5-HT2 receptors might not be
      primarily involved in the pathophysiology of schizophrenia.

PMID- 10894089
TI  - Effect of 1,25(OH)2D3 on expression of estrogen receptor-alpha mRNA on rat
      osteosarcoma cell line (ROS 17/2.8).
AB  - In order to investigate the regulatory mechanisms of estrogen receptors (ER) in
      bone cells, changes in ER-alpha mRNA levels of rat osteosarcoma cell line (ROS
      17/2.8) before and after exposure to 1,25(OH)2D3 and 17-beta estradiol
      respectively were measured by quantitative polymerase chain reaction using an
      internal standard. ER mRNA levels in the ROS 17/2.8 cultured with the medium
      alone had 5.029 +/- 1.623 mol/g total RNA x 10(-13) and were not statistically
      different from those cultured in the presence of 1,25(OH)2D3 at concentrations of
      10(-12) M and less. ER mRNA levels in the ROS 17/2.8 cell line showed a small but
      a significant increase as a result of stimulation by 1,25(OH)2D3 at
      concentrations of 10(-10) and 10(-11) M. However, ER mRNA levels in ROS 17/2.8
      cultured in the presence of 1,25(OH)2D3 at concentrations of 10(-9) M were not
      statistically different from those of the control. On the other hand, the
      expression of ER in ROS 17/2.8 cells cultured for 3 hours with various doses of
      1,25(OH)2D3 showed, by immunoblotting methods, a significant increase at the dose
      of 10(-10) M in the expression of ER. Although a physiological significance is
      obscure, these observations suggest that 1,25(OH)2D3 plays a part in the
      expression of ER in ROS 17/2.8. No significant changes were seen in the
      expression of ER mRNA and the synthesis of ER as a result of stimulation by the
      estradiol.

PMID- 10894090
TI  - Binding of mutant tissue-type plasminogen activators to human endothelial cells
      and their extracellular matrix.
AB  - We previously demonstrated that tissue-type plasminogen activator (t-PA)
      specifically bound to its receptor (t-PAR) on human umbilical vein endothelial
      cells (HUVEC). In addition to analyses of t-PA binding to plasminogen activator
      inhibitor-1 (PAI-1) in the extracellular matrix (ECM) and to the t-PAR, we
      further evaluated the binding of three t-PA mutants, deltaFE1X t-PA lacking
      finger (F), epidermal growth factor-like (E) domains and one sugar chain at
      Asn177 thus comprising two kringles (K1 and K2) and protease (P) domains,
      deltaFE3X t-PA with three glycosylation sites deleted at Asn117, 184, and 448,
      and deltaFEK1 t-PA comprising K2 and P domains without glycosylation. Wild-type t
      PA bound to ECM with high affinity, which was completely blocked by anti-PAI-1
      IgG. Wild-type t-PA, deltaFE1X t-PA and deltaFEK1 t-PA bound to two classes of
      binding sites with high and low affinities on monolayer HUVEC. However, all t-PAs
      bound to a single class of binding site in the presence of anti-PAI-1 IgG.
      DeltaFEK1 t-PA bound t-PAR maximally among these t-PAs. These results suggested
      that the high affinity binding of t-PA mainly occurred with PAI-1 on ECM while
      the low affinity binding was with t-PAR. The deletion of F, E domains and sugar
      chains had no effect on binding with t-PAR. However, since only K1-missing t-PA
      (deltaFEK1) exhibited significantly increased binding sites among these t-PAs, it
      was suggested that the binding to t-PAR was mediated mainly by K2 domain and that
      the increase of binding was due to direct exposure of K2 domain.

PMID- 10894091
TI  - Follicle selection in cyclic guinea pigs with active immunization against inhibin
      alpha-subunit.
AB  - Experiments were conducted to elucidate the mechanisms of active immunization
      against inhibin on ovarian follicular development and selection in guinea pigs.
      Estrous cycle was synchronized in experimental guinea pigs by implanting
      progesterone containing tubes. Antibodies that bound 125I-labeled bovine inhibin
      were produced by all guinea pigs receiving the inhibin vaccine (recombinant ovine
      alpha-subunit in oil emulsion) without any effects on duration of the estrous
      cycle. Active immunization against inhibin increased the plasma concentrations of
      progesterone during the luteal phase and the plasma concentrations of estradiol
      but failed to increase the plasma concentration of follicle-stimulating hormone
      (FSH) during preovulatory period. The treatment also increased the number of
      corpora lutea (from 1.3+/-0.3 to 7.0+/-1.6 per each ovary), and preovulatory
      sized follicles (from 1.8+/-0.6 to 7.0+/-1.6 per each ovary), and follicles
      stained positively for inhibin alpha-subunit (from 2.3+/-0.5 to 6.3+/-1.3 per
      each ovary) significantly. The results indicate that active immunization against
      inhibin enhances ovulation rate by affecting the follicle selection and only
      dominant follicle can be stained for inhibin alpha-subunit in guinea pigs. This
      study is firstly to provide direct evidence that inhibins play important role in
      follicle selections in guinea pigs.

PMID- 10894092
TI  - Cell surface NADH oxidase activity of brine shrimp oscillates with a period of 25
      min and is entrained by light.
AB  - Plants have a surface NADH oxidase that measures time by oscillating with a 24
      min period. The period is synchronized by light. With plants, a new maximum is
      observed exactly 12 min after the beginning of the light exposure. These
      experiments were to determine if animals exhibited a cell surface NADH oxidase
      having a similar periodicity and to answer the question, does the periodicity in
      animals respond to light? Using brine shrimp as a model, the findings show that
      plants and animals exhibit similar oscillating NADH oxidase activity and that the
      periodicity in this invertebrate animal does respond to light. Brine shrimp were
      grown for two to three days and transferred to darkness for 45 min. After return
      to light for one min, NADH was added and measurements of NADH oxidation were
      recorded over 50 min. The brine shrimp exhibited a cell surface NADH oxidase that
      oscillated with a period of 25 min. After being subjected to light, the brine
      shrimp showed a new maximum in NADH oxidation between 12 to 13 min after the
      beginning of the light exposure and again at 37 min and at 25 min intervals
      thereafter. The findings demonstrate that the periodic oscillations in NADH
      oxidation of brine shrimp are light entrainable.

PMID- 10894093
TI  - The ovarian and cervical regions of the rat uterus display a different
      contractile response to serotonin and prostaglandin F2alpha. I. The estrous
      cycle.
AB  - In pharmacological studies using isolated tissues, the sensitivity to different
      agonists may vary depending on the anatomical region. The aim of the present
      study was to evaluate the in vitro contractile response to serotonin,
      prostaglandin F2alpha, and oxytocin of the ovarian and the cervical uterine
      segments isolated from rats in the four different stages of the rat estrous
      cycle. Non-cumulative curves were recorded for both, the ovarian and the cervical
      uterine segments. The cervical portion displayed a higher contractile response to
      serotonin and a lower response to PGF2alpha than the ovarian portion. Oxytocin
      induced similar responses in both uterine segments. The uterine ovarian segment
      displayed a similar sensitivity to serotonin in all the estrous cycle stages,
      whereas in the cervical segment, influenced by estrogens in diestrus and
      proestrus, an increase in contractility was observed. According to these
      findings, serotonin might participate in the spermatozoa transport toward the
      oviduct. The higher response of the ovarian portion to prostaglandin F2alpha is
      in line with its role during labor and delivery.

PMID- 10894094
TI  - A novel kappa-opioid receptor agonist, TRK-820, blocks the development of
      physical dependence on morphine in mice.
AB  - The effects of a novel kappa-opioid receptor agonist, TRK-820, on the development
      of physical dependence on morphine were investigated in mice in comparison with
      those of U-50,488H. A marked body weight loss and several withdrawal signs were
      observed following naloxone challenge in morphine-dependent mice. Co-injection of
      TRK-820 (0.003-0.03 mg/kg, s.c.) but not U-50,488H (1-10 mg/kg, s.c.) during
      chronic morphine treatment dose-dependently suppressed the naloxone-precipitated
      body weight loss, jumping, wet dog shakes and diarrhea. These results suggest
      that TRK-820-sensitive kappa-opioid receptor subtypes may play a significant role
      in modulating the development of physical dependence on morphine.

PMID- 10894095
TI  - Inhibition of adipocyte lipolysis by papaverine: papaverine can inhibit the
      redistribution of hormone-sensitive lipase.
AB  - Papaverine, despite being a potent phosphodiesterase inhibitor, actually blocks
      adipocyte lipolysis. The present study was designed to clarify the mechanism of
      the inhibitory effect of papaverine on lipolysis. Lipolysis, stimulated by either
      10 microM isoproterenol or 5 mM dibutyryl cAMP, was significantly inhibited by
      papaverine (100 microM and above). Papaverine, however, did not affect the
      isoproterenol-induced increase in the protein kinase A (A-kinase) activity ratio.
      In cell-free extract from non-stimulated adipocytes, cAMP-stimulated A-kinase
      activities were almost completely blocked by H-89, a potent inhibitor of A
      kinase, but not by papaverine. Thus, the inhibitory effect of papaverine on
      lipolysis could be responsible for a deficit in step(s) distal to A-kinase
      activity. Hormone-sensitive lipase activities in the infranatant fraction of
      centrifuged homogenates of cells, which were maximally stimulated with
      isoproterenol were significantly reduced. This result indicates that hormone
      sensitive lipase redistributes from cytosol to its substrate in lipolytically
      stimulated cells. Papaverine completely blocked the isoproterenol-induced
      decrease in lipase activity in the infranatant fraction. These results suggest
      that papaverine blocks lipolysis through its inhibitory effect on the
      redistribution of hormone-sensitive lipase.

PMID- 10894096
TI  - Ciliary assessment in bronchiectasis.
AB  - Bronchiectasis is a common condition among the Oriental population and affected
      patients suffer from chronic sputum production punctuated by recurrent infective
      exacerbations. Cilia are minute structures present on the surface of respiratory
      and other epithelial cells that beat continuously to maintain a sterile mucosal
      surface in the respiratory tract. Patients with primary ciliary dyskinesia could
      potentially develop recurrent sinotrachrobronchitis, bronchiectasis, serous
      otitis media, hydrocephalus, and male infertility. The assessment of cilia has,
      however, received little attention until recently and generally involves
      elaborate methods that require complex and expensive technology. This brief
      article discusses application of the saccharine test, light microscopy assessment
      of ciliary beat, and transmission electron microscopy assessment of the
      ultrastructure of cilia. The rationale and indications for ciliary assessment are
      also listed along with illustrations showing ciliary structure, equipment
      required for sampling and assessment of cilia, and transmission electron
      micrographs of ciliary ultrastructural abnormalities.

PMID- 10894097
TI  - A comparative study of pleurodesis using talc slurry and bleomycin in the
      management of malignant pleural effusions.
AB  - OBJECTIVE: Differing success rates of various pleurodesis agents have been
      reported in the management of malignant pleural effusions. A randomized clinical
      trial was conducted to compare the efficacy of two commonly used agents, talc and
      bleomycin, for the pleurodesis of malignant pleural effusions. METHODOLOGY:
      Inclusion in the study required proof of a malignant pleural effusion by fluid
      cytology or pleural biopsy. Exclusion criteria included trapped lung, loculated
      effusions, recurrent effusions and life expectancy < 1 month. Five grams of talc
      or 1 unit per kilogram bodyweight of bleomycin mixed in 150 mL of normal saline
      was administered via tube thoracostomy after complete drainage of the pleural
      effusion in each patient. Treatment success was defined as the absence of
      recurrent pleural effusion on the chest radiograph 1 month after pleurodesis.
      RESULTS: Treatment success was achieved in 16 out of 18 patients (89%) in the
      talc slurry group versus 14 out of 20 patients (70%) in the bleomycin group
      (P=0.168). Fever and pain were the only side-effects of pleurodesis in both
      groups. CONCLUSION: These results indicate that talc slurry is as effective as
      bleomycin in preventing early recurrence of malignant pleural effusions.
      Pleurodesis with talc instead of bleomycin can result in significant cost
      savings.

PMID- 10894098
TI  - Cartilaginous injury limits cryopreservation of tracheal isograft.
AB  - OBJECTIVE: Histological recovery of tracheal grafts after cryopreservation was
      investigated using a rat heterotopic tracheal transplant model in order to
      evaluate the clinical applicability of tracheal cryopreservation. METHODOLOGY:
      Heterotopic syngeneic tracheal transplantation was performed between F344 rats.
      Recipient animals received either a non-cryopreserved or a cryopreserved tracheal
      graft for direct comparison with regard to the effect of cryo-injury. In the non
      cryopreserved group (CP(-)), tracheal segments were transplanted syngeneically
      between F344 rats immediately after harvest. Grafts were implanted into the
      abdominal space and wrapped with the greater omentum. In the cryopreserved group
      (CP(+)), grafts were implanted after cryopreservation for 7 days at -85 degrees
      C. Recipient rats were killed on days 7, 14, 21, 28, and at 2 months after
      surgery. Epithelial regeneration and cartilage changes were evaluated using a
      semiquantitative four grade scoring system. RESULTS: Squamous epithelium without
      ciliated structure was observed on day 7 in both groups. Bronchial epithelium was
      then regenerated gradually and normally ciliated epithelium was observed on day
      28 in both groups. The condition of the epithelium was still well maintained in
      the CP(-) group at 2 months post-transplantation; however, a severe epithelial
      defect was observed in the CP(+) group. Bronchial cartilage showed a normal shape
      and mostly viable chondrocytes with proliferative cell nuclear antigen (PCNA)
      positive staining at all time points in the CP(-) group until 2 months after
      surgery. However, in the CP(+) group, a massive loss of viable chondrocytes was
      observed at 2 months post-transplantation. Macroscopically, CP(+) grafts showed a
      diminished structure without satisfactory airway lumen at 2 months. CONCLUSION:
      The epithelium of a tracheal graft can be temporarily recovered after
      implantation followed by 7 days cryopreservation. However, bronchial cartilage
      may be severely damaged by freezing, which results in late destruction with loss
      of viable chondrocytes. It is suggested here that establishing a method of safe
      cryopreservation for tracheal cartilage will be imperative to making tracheal
      cryopreservation possible.

PMID- 10894099
TI  - Bronchial responsiveness to beta-adrenergic stimulation and enhanced beta
      blockade in asthma.
AB  - OBJECTIVE: Beta-adrenergic blocking drugs have no effect on the airways of normal
      subjects but in asthma even small doses may cause severe deterioration. A
      seemingly obvious explanation for this abnormal sensitivity is that asthmatic
      airways, but not normal airways, are tonically dilated by the sympatho-adrenal
      system. However, studies suggest that sympatho-adrenal activity is normal in
      asthma, as is bronchial sensitivity to beta-agonists. The present study re
      examines bronchial beta-adrenergic sensitivity in asthma and also measures
      antagonism produced in normal and asthmatic bronchi by a beta-blocking drug.
      METHODOLOGY: The threshold bronchodilator doses of inhaled isoprenaline (dose
      required for a 35% increase in specific airway conductance 'PD35') was measured
      in 11 normal and 14 asthmatic adults on two separate occasions. After
      administering propranolol (inhaled or intravenously) PD35 was remeasured.
      RESULTS: Sensitivity to isoprenaline was greater in symptomatic asthmatics (PD35
      = 0.003 micromol) than in asymptomatic asthmatics (PD35 = 0.021 micromol) and in
      non-asthmatics (PD35 = 0.123 micromol; P < 0.001 in each case). Symptomatic
      asthmatics also showed 66-fold more antagonism than non-asthmatics when they were
      given propranolol by inhalation (P < 0.001) and sixfold more with intravenous
      propranolol (P = 0.005). CONCLUSIONS: The increased sensitivity of asthmatics to
      inhaled isoprenaline suggests that they may also be more sensitive to their
      endogenous adrenaline, which may thus dilate and stabilize their airways. Taken
      with enhanced antagonism by propranolol, this provides insight into the
      aggravation of asthma by beta-blocking drugs.

PMID- 10894100
TI  - Computed tomography or ultrasonically guided pigtail catheter drainage in
      multiloculated pleural empyema: a recommended procedure?
AB  - OBJECTIVES: The role of image-guided pigtail catheter drainage in the treatment
      of pleural empyema is associated with different outcomes, dependent on the stage
      of the disease. No agreement concerning its use exists. METHODOLOGY: Fourteen
      patients at a fibropurulent stage of pleural empyema initially treated with
      computed tomography (CT) or ultrasonically guided pigtail catheter drainage were
      reviewed. All patients were admitted with clinical symptoms of sepsis. Chest X
      ray, CT scan and/or ultrasonography and thoracentesis with biochemical
      examination revealed multiloculated pleural empyema. Despite the diagnosis of
      multiloculated empyema, CT or ultrasonically guided pigtail catheter drainage was
      performed. However, septic symptoms deteriorated and all cases proceeded to
      thoracotomy with decortication. RESULTS: Image-guided drainage failed in all
      patients. Septic symptoms disappeared within 24-48 h after decortication. The
      patients recovered without sequela, were discharged 6-15 days (mean: 9.2 days)
      postoperatively and were able to return to normal physical activity. CONCLUSIONS:
      Computed tomography or ultrasonically guided pigtail catheter drainage can not be
      recommended in the case of a fibropurulent stage of empyema thoracis.

PMID- 10894101
TI  - Post-inhalation bronchoconstriction by beclomethasone dipropionate: a comparison
      of two different CFC propellant formulations in asthmatics.
AB  - OBJECTIVE: To assess the change in bronchial response to cumulative doses from
      two beclomethasone dipropionate metered-dose inhalers (MDI), each using
      chlorofluorocarbon (CFC) propellants, in asthma patients previously showing falls
      in forced expiratory volume in 1 s (FEV1) shortly after exposure to
      beclomethasone MDI. METHODOLOGY: A total of 18 patients were randomized to a
      single-blind, three-period cross-over treatment regimen, whereby each was
      administered increasing doses of control mixture (containing surfactant and CFC
      propellants) or beclomethasone, formulated as either Becloforte or Respocort (250
      1000 microg per dose; cumulative dose 2000 microg). Bronchial response was
      measured by comparison of FEV1 values pre- and post-inhalation. RESULTS:
      Respocort formulation produced the least post-dose mean maximum reduction in FEV1
      (0.36 +/- 0.17 L; 14.3 +/- 7.2% of baseline FEV1), while the reduction caused by
      the control was similar (0.40 +/- 0.18 L; 16.2 +/- 9.9% of baseline FEV1).
      Becloforte produced a significantly greater maximum reduction in FEV1 than
      Respocort (0.55 +/- 0.32 L, P = 0.003; 22.0 +/- 15.3% of baseline FEV1, P =
      0.005). No serious adverse events were reported, but four patients experienced
      falls in FEV1 of greater than 15% (three on Becloforte, one using the control).
      CONCLUSION: The incidence of falls in FEV1 following use of beclomethasone MDI
      was low and generally not serious even in a selected population. The Becloforte
      preparation produced significantly more post-dose bronchoconstriction than the
      Respocort formulation, perhaps because of differences in the composition of the
      surfactant and/or CFC propellant mixtures used to formulate each of the aerosols.

PMID- 10894102
TI  - Reperfusion lung injury after unilateral pulmonary artery occlusion.
AB  - OBJECTIVE: To test the hypothesis that reperfusion of the canine lung after 1
      week of vascular occlusion results in acute injury of the reperfused lung with
      concurrent impairment in gas exchange. METHODOLOGY: In 11 conditioned dogs, the
      left pulmonary artery was completely occluded by a vascular clip placed at
      thoracotomy. One week later, at repeat thoracotomy, the clip was removed in six
      animals (reperfused group) but left in place in five (sham group).
      Bronchoalveolar lavage fluid (BAL) components, gas exchange, haemodynamics and
      histological alterations were examined. RESULTS: During occlusion, the mean
      pulmonary artery pressure and pulmonary vascular resistance increased
      significantly, and after 6 days there was a significant increase in ventilation
      to high ventilation perfusion ratio (V/Q) areas. With reperfusion, the previously
      occluded lung demonstrated, in comparison to the contralateral lung, a
      significant increase in BAL cellularity and neutrophil fraction, gross and
      histological evidence of oedema, and impaired surfactant activity. Shunt
      fraction, measured by the inert gas technique, also increased only after
      reperfusion, although mild hypoxaemia occurred in both groups. Endothelial
      abnormalities and perivascular oedema were noted in both groups, but were more
      marked in the reperfused lungs. CONCLUSION: Reperfusion of the canine lung after
      1 week of complete occlusion resulted in evidence of mild acute lung injury. The
      aetiology of this injury was multifactorial.

PMID- 10894103
TI  - Antigen uptake and subsequent cell kinetics in bronchus-associated lymphoid
      tissue.
AB  - OBJECTIVE: Bronchus-associated lymphoid tissue (BALT) plays an important role in
      the immunological defence of airways. However, the mechanisms of BALT
      development, antigen sampling, and subsequent cell kinetics remain unclear. To
      clarify these chronological processes, we used a Pseudomonas aeruginosa-exposed
      mouse model. METHODOLOGY: In BALB/c and C57BL/6 mice, BALT development was
      induced by inhalation of heat-killed P. aeruginosa after sensitization with
      subcutaneous injection of P. aeruginosa in the presence of Freund's complete
      adjuvant. Subsequently, we chronologically killed these mice who had inhaled
      PKH26-labelled P. aeruginosa and examined bacterial transport using fluorescence
      microscopy. The distribution of interleukin-4-positive cells and interferon-gamma
      positive cells was studied immunohistochemically. RESULTS: The degree of BALT
      hyperplasia was greater in sensitized mice than in non-sensitized mice and in
      BALB/c mice than in C57BL/6 mice. PKH26-labelled bacteria were found in BALT
      earlier in sensitized mice than in non-sensitized mice. Immunohistochemical
      studies revealed that interleukin-4-positive cells predominated over interferon
      gamma-positive cells in the peripheral areas of lymphoid follicles. CONCLUSION:
      These results indicate that administered antigens are actively transported into
      BALT and that sensitized Th2 lymphocytes play an important role in forming and
      maintaining BALT.

PMID- 10894104
TI  - Pulmonary tissue volume measured by acetylene rebreathing under artificial
      ventilation.
AB  - OBJECTIVE: In order to evaluate the pulmonary congestive state of patients being
      mechanically ventilated, an acetylene rebreathing method was employed.
      Measurement of pulmonary tissue volume by the acetylene (C2H2) rebreathing method
      was performed in 15 patients under artificial ventilation including four
      congestive heart failure cases, one renal failure case, and 12 healthy controls.
      METHODOLOGY: The subjects rebreathed mixed gas containing 0.65% C2H2, 10% argon
      (Ar), and 60% oxygen (O2) from end-tidal level, and inspiratory and expiratory
      gas concentrations were measured by a mass spectrometer. Correction for system
      volume reduction during rebreathing due to gas exchange and C2H2 concentration
      fluctuation was performed, pulmonary tissue volume was calculated from the C2H2
      and Ar concentration difference at the time zero intercept. Time zero was assumed
      to be the time at which C2H2 and Ar concentration started to differ. RESULTS:
      Pulmonary tissue volume per functional residual capacity and pulmonary tissue
      volume per pulmonary capillary blood flow for cases with congestive heart failure
      and renal failure cases were significantly higher than those for non-pulmonary
      congestion cases and normal controls. CONCLUSION: The measurement of pulmonary
      tissue volume by C2H2 rebreathing can be applied to the patients under artificial
      ventilation in order to quantitatively evaluate pulmonary congestion or edema.

PMID- 10894105
TI  - Cytokines enhance airway smooth muscle contractility in response to acetylcholine
      and neurokinin A.
AB  - OBJECTIVE: In vivo airway hyperresponsiveness has been demonstrated following
      inhalation of specific cytokines in normal individuals. Whether this airway
      hyperresponsiveness results from a direct effect of cytokines on airway smooth
      muscle contractility, or via changes in airway wall structure is not known. The
      aim of the present study was to determine the effect of the pro-inflammatory
      cytokines interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF
      alpha) on airway smooth muscle contractility in vitro. METHODOLOGY: Ovine
      tracheal smooth muscle strips were incubated for 18 h at room temperature in
      Dulbecco's modified Eagle's medium, supplemented with antibiotics, with IL-1beta
      (10 ng/mL) and TNF-alpha (100 ng/mL), in an atmosphere of 5%CO2:95%O2. Following
      incubation cumulative concentration-response curves to acetylcholine (ACh) and
      neurokinin A (NKA) were obtained. Antagonist affinity studies were performed to
      determine whether the cytokine-induced enhanced contractility to ACh and NKA
      resulted from a functional alteration to specific M3 and NK2 receptors.
      Cumulative concentration-response curves to NKA were performed in the presence of
      phosphoramidon to determine if the enhanced contractility to NKA following
      cytokine exposure was due to a reduction in endogenous neutral endopeptidase
      activity. To assess the calcium dependence of the hyperresponsiveness, cumulative
      concentration-responses to ACh were conducted in calcium-free Krebs'-Henseleit
      solution. RESULTS: Pre-incubation with TNF-alpha and IL-1beta caused a
      significant leftward shift, and an increase in the magnitude, of the
      concentration-response curves to both ACh and NKA. No difference in M3 and NK2
      receptor antagonist affinity (pA2) values between the control and cytokine
      treated tissue was observed. Neurokinin A contractility in the presence of
      phosphoramidon indicated that the enhanced contractility following cytokine
      exposure was not due to a reduction in endogenous neutral endopeptidase activity.
      Removal of extracellular calcium ions attenuated the contractile response to low
      concentrations of ACh in the control and cytokine-pretreated tissue. However,
      enhanced contractility following TNF-alpha and IL-1beta pretreatment was still
      present. CONCLUSION: Pro-inflammatory cytokines induce in vitro
      hyperresponsiveness in normal airway smooth muscle via a mechanism involving
      intracellular calcium mobilization.

PMID- 10894106
TI  - Psittacosis with increased gammadelta T cells in bronchoalveolar lavage fluid.
AB  - Experience with two cases of psittacosis is described here in which the number of
      gammadelta T cell receptor-positive T lymphocytes (gammadelta T cell) in the
      bronchoalveolar lavage fluid was markedly increased (25.1 and 66.9%) and CD8+ T
      cells were also increased with reversal of the CD4/CD8 ratio. These values
      improved to the normal range along with recovery of their radiographical
      findings. The present findings suggest that gammadelta T cells may play an
      important role in protection from lung injury caused by Chlamydia psittaci
      infection.

PMID- 10894107
TI  - Impact of haze from forest fire to respiratory health: Indonesian experience.
AB  - OBJECTIVE: This paper will describe the impact on the human lung of haze from
      forest fires in Indonesia based on data collected from different provinces.
      METHODOLOGY: Data were collected from personal reports from pulmonologists
      working in the area as well as from province/district health offices and
      hospitals. RESULTS: These data show that there was a significant impact of haze
      to the human lung. There was a significant increase in respiratory conditions,
      lung function complaints and other related impacts. CONCLUSION: Further studies,
      especially cohort studies, should be undertaken so that the long-term' impact of
      pollution from forest fires can be known.

PMID- 10894108
TI  - Impact to lung health of haze from forest fires: the Singapore experience.
AB  - OBJECTIVE: From late July to the beginning of October 1997, countries of
      Southeast Asia experienced severe smoke haze pollution from uncontrolled forest
      fires mainly in the Indonesian states of Kalimantan and Sumatra. In Singapore,
      the impact of the 1997 haze was felt in the period from the end of August to the
      first week of November 1997 as a result of prevailing winds. METHODOLOGY: The
      Ministry of the Environment monitors ambient air quality by a country-wide
      telemetric air quality monitoring and management network, with 15 stations
      located throughout the island, linked via a public telephone network to a central
      control station at the Environment Building. The monitoring methods used are the
      United States Environmental Protection Agency (USEPA) reference methods. The
      Pollutant Standards Index (PSI) developed by the USEPA is used for the reporting
      of daily air pollution concentrations. Intervals on the PSI scale are related to
      the potential health effects of the daily measured concentrations of the five
      major air pollutants: sulfur dioxide, particulate matter (PM10), nitrogen
      dioxide, ozone and carbon monoxide. Public sector health facilities which come
      under the Ministry of Health, have computerized patient care systems which enable
      the routine ongoing surveillance of disease conditions for the period of the
      haze. Attention during the period of the haze was focused on conditions related
      to health effects of the haze. Data sources for the monitoring of the lung health
      effects of the haze included morbidity from public sector outpatient care
      facilities, accidents and emergency departments, public sector inpatient care
      facilities and national mortality data. RESULTS: Findings from the health impact
      of the haze showed that there was a 30% increase in outpatient attendance for
      haze-related conditions. An increase in PM10 levels from 50 microg/m3 to 150
      microg/m3 was significantly associated with increases of 12% of upper respiratory
      tract illness, 19% asthma and 26% rhinitis. Supplementary findings from scanning
      the electron microscopic sizing of the haze particles showed that 94% of the
      particles in the haze were below 2.5 microm in diameter. This was consistent with
      emissions from combustion sources originating over 500 km from Singapore. This
      has been of some concern because particles smaller than 2.5 microm in diameter
      can easily bypass normal body defence metabolism and penetrate deeply into the
      alveoli of the lungs. During the same period, there was also an increase in
      accident and emergency attendance for haze-related conditions. There was no
      significant increase in hospital admissions or in mortality. CONCLUSION: The
      present study found that the health effects from the 1997 smoke haze in Singapore
      were generally mild.

PMID- 10894109
TI  - Air quality in Malaysia: impacts, management issues and future challenges.
AB  - OBJECTIVE: Observations have been made on the long-term trends of major air
      pollutants in Malaysia including nitrogen dioxide, carbon monoxide, the ozone and
      total suspended particulate matter (particularly PM10), and sulfur dioxide,
      emitted from industrial and urban areas from early 1970s until late 1998.
      METHODOLOGY: The data show that the status of atmospheric environment in
      Malaysia, in particular in highly industrialized areas such as Klang Valley, was
      determined both by local and transboundary emissions and could be described as
      haze and non-haze periods. RESULTS: During the non-haze periods, vehicular
      emissions accounted for more than 70% of the total emissions in the urban areas
      and have demonstrated two peaks in the diurnal variations of the aforementioned
      air pollutants, except ozone. The morning 'rush-hour' peak was mainly due to
      vehicle emissions, while the late evening peak was mainly attributed to
      meteorological conditions, particularly atmospheric stability and wind speed.
      Total suspended particulate matter was the main pollutant with its concentrations
      at few sites often exceeding the Recommended Malaysia Air Quality Guidelines. The
      levels of other pollutants were generally within the guidelines. Since 1980, six
      major haze episodes were officially reported in Malaysia: April 1983, August
      1990, June 1991, October 1991, August to October 1994, and July to October 1997.
      The 1997 haze episode was the worst ever experienced by the country. Short-term
      observations using continuous monitoring systems during the haze episodes during
      these periods clearly showed that suspended particulate matter (PM10) was the
      main cause of haze and was transboundary in nature. Large forest fires in parts
      of Sumatra and Kalimantan during the haze period, clearly evident in satellite
      images, were identified as the probable key sources of the widespread heavy haze
      that extended across Southeast Asia from Indonesia to Singapore, Malaysia and
      Brunei. The results of several studies have also provided strong evidence that
      biomass burning is the dominating source of particulate matter. The severity and
      extent of 1997's haze pollution was unprecedented, affecting some 300 million
      people across the region. The amount of economic costs suffered by Southeast
      Asian countries during this environmental disaster was enormous and is yet to be
      fully determined. Among the important sectors severely affected were air and land
      transport, shipping, construction, tourism and agro-based industries. The
      economic cost of the haze-related damage to Malaysia presented in this study
      include short-term health costs, production losses, tourism-related losses and
      the cost of avertive action. Although the cost reported here is likely to be
      underestimated, they are nevertheless significant (roughly RM1 billion).
      CONCLUSIONS: The general air quality of Malaysia since 1970 has deteriorated.
      Studies have shown that should no effective countermeasures be introduced, the
      emissions of sulfur dioxide, nitrogen oxides, particulate matter, hydrocarbons
      and carbon monoxide in the year 2005 would increase by 1.4, 2.12, 1.47 and 2.27
      times, respectively, from the 1992 levels.

PMID- 10894110
TI  - Diesel exhaust particles activate human bronchial epithelial cells to express
      inflammatory mediators in the airways: a review.
AB  - OBJECTIVE: Epidemiological as well as experimental studies suggest that
      particulate air pollutants, including diesel exhaust particles (DEP), may play a
      role in the recent increase of respiratory morbidity and mortality. We studied
      the effect of DEP on the production of inflammatory cytokines and mediators
      including IL-8 and granulocyte macrophage colony stimulating factor (GM-CSF) by
      human airway epithelial cells in vitro. METHODOLOGY: Suspended DEP were added to
      cultured normal human bronchial epithelial cells or transformed BEAS-2B cells.
      The release of cytokines and mediators was evaluated by enzyme-linked
      immunosorbent assay. The transcriptional levels of IL-8 mRNA was studied by
      northern blot analysis and run-on transcription assay. Activation of
      transcription factors was assessed by electrophoretic mobility shift assay.
      RESULTS: Non-toxic doses of suspended DEP showed a significant stimulatory effect
      on IL-8 and GM-CSF production by airway epithelial cells. Diesel exhaust
      particles increased the steady-state levels of IL-8 mRNA, which was suggested to
      be largely due to increased transcriptional rates. Electrophoretic mobility shift
      assay demonstrated that DEP induced increased binding to the specific motif of
      nuclear factor (NF)-kappaB, but not of transcription factor AP-1. Both N
      acetylcysteine and pyrrolidine dithiocarbamate attenuated the action of DEP on IL
      8 mRNA expression, suggesting that oxidant-mediated pathway might be involved in
      its processes. Transient transfection of airway epithelial cells with wild and NF
      kappaB binding motifs indicated that the activation of NF-kappaB was essential
      for IL-8 gene upregulation by reporter gene assay. CONCLUSIONS: These results
      suggested that DEP activate NF-kappaB, which might be an important pathway for
      the expression of inflammatory cytokines in vitro.

PMID- 10894111
TI  - Characteristic modifications of the peripheral airways in patients with bronchial
      asthma in areas with air pollution.
AB  - OBJECTIVE: Changes in the peripheral airways in patients with bronchial asthma
      who were living in the Kawasaki industrial zone, region with severe air
      pollution, were morphologically investigated in order to determine the
      pathological conditions of such bronchial asthma, in particular ascertaining the
      effect of air pollution. METHODOLOGY: Studies were made of the morphological
      characteristics of the peripheral airways in patients with bronchial asthma who
      had resided for long periods in an area near Tokyo affected by air pollution.
      RESULTS: The endoscopic findings of the peripheral airways were distinct,
      consisting of reddening, stenosis, pigmentation, pallor, lustrelessness and
      hypersecretion. The histological findings also differed from those in usual forms
      of asthma. CONCLUSIONS: The bronchial asthma in the present patients appeared to
      be a totally different form from a morphological viewpoint, although it was quite
      similar to known types in its clinicophysiological features.

PMID- 10894112
TI  - Translational suppression by hammerhead ribozymes and inactive variants in S.
      cerevisiae.
AB  - The activity of hammerhead ribozymes in S. cerevisiae was assessed using two
      ribozymes that were designed to intramolecularly attack the hepatitis B viral X
      mRNA. The ribozymes effectively suppressed the expression of the X-lacZ fusion
      gene, when they were inserted at the 5' end of the X mRNA. The ribozymes cleaved
      the target RNA efficiently at the targeted phosphodiester bond, but the inactive
      mutants carrying G5-to-A substitution in the core did not, as the total RNA
      preparations of yeast extracts was assayed by primer extension. These G5A
      mutants, however, exerted the suppression as effectively as the wild-type
      ribozymes. The results, with several mutations introduced to a ribozyme,
      suggested that either mere formation of hammerhead-like structures with the three
      stems, or the formation of any two stems, could inhibit translation. Thus, the
      hammerhead-like structures, leading to cleavage or not, could effectively
      suppress translation, especially when formed around the initiation codon. The G5
      to-A and U7-to-G mutations and replacement of the stem-II hairpin tetraloop did
      not appear to affect the formation of the inhibitory structure(s). The inhibition
      that was observed when stems I and III were directly connected without a loop or
      with a stem II hairpin was completely relieved when they were connected with only
      the loop of stem II (not containing the stem portion).

PMID- 10894113
TI  - Bacteriophage SP6 RNA polymerase mutants with altered termination efficiency and
      elongation processivity.
AB  - An Escherichia coli strain containing two plasmids was developed for in vivo
      isolation of the phage SP6 RNA polymerase mutants. It was developed to isolate
      mutants with increased proficiency of termination at the SP6 terminator and/or
      with reduced elongation processivity. Mutations were randomly introduced into an
      N-terminal third of the polymerase gene that was placed under a lac promoter in
      one plasmid. In the other plasmid, a promoter-lacking lacZ gene modified for
      reduced translation efficiency was placed downstream of a tandem pair of the SP6
      terminator located downstream of an SP6 promoter-chloramphenicol
      acetyltransferase gene. Termination-up mutants were selected in vivo as they
      rendered LacZ activity level lower than the wild-type, without reducing
      chloramphenicol resistance substantially. Three such mutants (M15L, M15S, and
      D117G) were purified, and their termination efficiencies were measured in vitro
      at two different intrinsic termination signals in the E. coli rrnB terminator t1
      that are different in requiring RNA hairpin formation. All three mutations
      enhanced termination efficiencies in vitro at the SP6 terminator and the upstream
      signal of rrnB t1, but reduced the efficiency at the downstream signal of it. All
      the mutations reduced elongation processivity, as the mutants produced much less
      amounts of large transcripts (2.1 kb) than the wild-type but the similar amounts
      of small transcripts (up to 670 nt). Thus, the mutations, all reducing elongation
      processivity of the polymerase, exhibited opposite effects on the two types of
      intrinsic termination signals, suggesting that the two mechanisms involve
      different interactions with the phage RNA polymerase.

PMID- 10894114
TI  - Mitochondrial DNA sequences of greenbug (Homoptera: Aphididae) biotypes.
AB  - Sequence comparisons were made for 738-bp of mtDNA cloned from seven greenbug,
      Schizaphis graminum, biotypes (B, C, E, F, G, H and I) obtained from laboratory
      colonies maintained by USDA-ARS, Stillwater, OK. These sequences include parts of
      the genes for 16S ribosomal subunit (16S rRNA), tRNAleu, tRNAser, cytochrome b
      (cytb) and NADH dehydrogenase (ND) subunits one and four. Sequence data revealed
      considerable variation in 86 (12%) nucleotide sites over the 738-bp sequenced
      among the seven greenbug biotypes. Nucleotide invariance was observed within the
      seven greenbug biotypes from both the laboratory colonies and field collected
      biotype E greenbugs from Kansas, Nebraska, Oklahoma, and Texas.

PMID- 10894115
TI  - Human glutathione-S-transferase: cloning and expression in Lactococcus lactis.
AB  - The glutathione-S-transferase A1 cDNA was amplified from the total RNAs of human
      liver by RT-PCR, and inserted into plasmid pMG36e. The hGSTA1 was expressed in
      Lactococcus lactis MG1363 and verified by SDS-PAGE and Western blot, purified by
      affinity chromatography and showed enzymatic activity.

PMID- 10894116
TI  - Tissue-/stage-dependent expression of a cloned Bombyx mandarina QM homologue.
AB  - QM, a novel gene that was firstly isolated as a putative tumor suppressor gene
      from Wilms' tumor cell line. Although it is well known that the QM gene product
      plays an important role within the tumor cells, the precise role of QM in the non
      tumor cells has remained elusive. With in this mind we isolated a cDNA encoding
      QM homologue from Bombyx mandarina to understand the function of QM. The 596 bp
      cDNA has an open reading frame of 219 amino acids and a predicted mol. wt. of 25
      kDa. The protein has more than 88% amino acid sequence identity to the QM protein
      from Drosophila melanogaster. mRNA expression gradually increased from 1-2 days
      after egg laying to 2 days of finial instar, while very low expressions were
      detected for either the pupae and the moth stages. The organs, posterior/middle
      division of silkgland, midgut, fat body and malpighian tubes, also show
      relatively high mRNA expression levels, respectively. The high degree of
      conservation and expression of the B. mandarina QM homologous suggest that it has
      a selectively conserved amino acid sequence due, presumably, to an important
      biological role which is associated with pupae formation.

PMID- 10894117
TI  - Age difference in the metabolism of p-bromophenylacetylurea in the rat: an
      implication for age-related susceptibility to its neurotoxicity.
AB  - p-Bromophenylacetylurea (BPAU)-induced delayed neuropathy showed an age-dependent
      susceptibility in rats. This study investigated the difference in BPAU metabolism
      in rats of two different ages to explore the metabolic aspect in age-dependent
      susceptibility to BPAU-induced neurotoxicity. Either 6-week or 1-year old F344
      male rats (n = 4) were given a single oral dose of 150 mg/kg BPAU. BPAU and its
      metabolites, N'-hydroxy-p-bromophenylacetylurea (HBPAU) and 4-(4-bromophenyl)-3
      oxapyrrolidine-2,5-dione (BPOPD), in serum, liver, brain and spinal cord were
      determined by HPLC 18 hr after dosing. The results showed that the levels of BPAU
      and HBPAU in the tissues of 1-year old rats were generally higher than those in
      the corresponding tissues of 6-week old rats. The levels of both BPAU and HBPAU
      in the spinal cord of the 1-year old rats were higher than those of the 6-week
      old rats (p < 0.05). In the serum, the concentration of BPOPD in the 6-week old
      rats was higher than that in the 1-year old rats (p < 0.01), whereas the HBPAU
      levels in the serum of 6-week old rats was significantly lower than that in the 1
      year old rats (p < 0.05). Thus the 6-week old rats metabolized BPAU more
      efficiently by producing more BPOPD, a detoxified metabolite, and less HBPAU, a
      suspected toxic metabolite, than the 1-year old rats. This suggests that the same
      dosage of BPAU may produce less severe initial lesions in young animals than in
      adults, and hence young animals exhibit more resistance to BPAU-induced
      neurotoxicity than adult rats. Therefore, metabolic differences between young and
      adult rats may be responsible for their age-related susceptibility to BPAU
      induced neurotoxicity.

PMID- 10894118
TI  - Induction of permeability transition and swelling of rat brain mitochondria by
      glutamine.
AB  - Exposure of rat cerebral mitochondria to 2-10 mM glutamine (Gln) for 20 min,
      produced a concentration-dependent, gradual decrease of light scattering
      reflecting mitochondrial swelling. The light scattering decreasing effect of 5 mM
      Gln was attenuated by 0.5 microM cyclosporin A (CsA), an inhibitor of
      mitochondrial permeability transition (mPT) induction. Histidine (His), which is
      a potent inhibitor of high affinity Gln uptake to mitochondria, attenuated Gln
      induced decrease of mitochondrial light scattering when added at equimolar
      concentration, and abolished the decrease when added at 15 mM concentration
      shortly before addition of Gln. His inhibited the uptake of 5 mM [14C]Gln in a
      concentration-dependent manner as measured during 3 min incubation. CsA did
      neither affect [14C]Gln uptake nor modified its inhibition by His. The effects of
      5 mM His and 0.5 microM CsA on mitochondrial light scattering were additive,
      indicating that mitochondrial swelling represents a cumulative effect of Gln 
      driven entry of osmotically obligated water and induction of mPT. Addition of
      ammonium ions at neurotoxic concentrations neither influenced the decrease of
      light scattering induced by Gln, nor produced any change in light scattering when
      added alone. The results point to mitochondrial swelling and subsequent
      activation of mPT, as one of the potential mechanisms by which Gln induces
      metabolic disturbances in the brain in hyperammonemic conditions.

PMID- 10894119
TI  - Blood lead and hemoglobin levels in Andean children with chronic lead
      intoxication.
AB  - This study investigated blood lead (PbB) and hemoglobin (HbB) levels in 88
      children (42 females and 46 males; ages: 2-15 years; mean age: 7.2) with chronic
      Pb exposure, living in a highly Pb-contaminated Andean village at above 2800
      meters. The mean PbB level for 88 venous blood samples was 43.2 microg/dl (SD:
      25.1; range: 6.2 - 128.2 microg/dl) measured by ICP-MS, and 42.0 microg/dl (SD:
      26.0; range: 5.0 - 130.0 microg/dl) by GFAAS analysis. The mean PbB level for the
      42 females was 41.0 microg/dl and for 46 males, 45.0 microg/dl. Multiple
      regression analysis showed a significant gender by age interaction (R2 = 0.099; F
      = 4.173, p = 0.044), indicating a relationship between age and PbB level for
      males, but not for females. Simple regression analysis showed a statistically
      significant positive correlation between PbB levels and age for males (r = 0.416,
      p = 0.004), but not for females (r = -0.042, p = .793). The measured mean HbB
      level for the 88 children was 12.6 g/dl (12.5 g/dl for females and 12.8 g/dl for
      males) and lower than expected for children living in the Ecuadorian Andes. The
      mean altitude-corrected HbB level was 10.9 g/dl (10.8 g/dl for females and 11.1
      g/dl for males). A significant inverse correlation between PbB and HbB levels was
      observed for the group of 88 children (r = -0.292, p = 0.006). Multiple
      regression analyses indicated no significant age and gender interaction (R2 =
      0.014; F = 0.025, p = 0.876) for HbB levels. In conclusion, the results of this
      investigation indicate that the children in this Pb-contaminated, high altitude
      study area had chronic elevated PbB levels, which increased with age for males,
      and probable Pb-induced anemia.

PMID- 10894120
TI  - Ethylenebisdithiocarbamate enhances MPTP-induced striatal dopamine depletion in
      mice.
AB  - Diethyldithiocarbamate (DDC) has been shown to enhance 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-induced striatal dopamine depletion in mice.
      Surprisingly, although DDC is a prototypic member of a class of compounds called
      dithiocarbamates (DTCs) that are widely used in industry and agriculture, only
      one study has investigated the interaction of dithiocarbamates other than DDC
      with MPTP. The purpose of the present study was to investigate whether two other
      widely used dithiocarbamates, ethylenebisdithiocarbamate (EBDC) and
      methyldithiocarbamate (MDC), would also enhance MPTP toxicity. The
      dithiocarbamates were administered to mice intraperitoneally at various doses
      with or without MPTP. Doses were chosen based on the LD50 values for each
      compound. DDC was also tested (using a previously reported dose) for comparison.
      Striata were obtained one week later for dopamine measurements. Consistent with
      previous reports, DDC produced statistically significant enhancement in MPTP
      induced striatal dopamine depletion. EBDC also produced significant exacerbation
      of MPTP-induced dopamine depletion. In contrast to DDC and EBDC, MDC failed to
      enhance the effects of MPTP, even when administered at doses of high lethality.
      Further studies of the dithiocarbamate class of compounds may help to elucidate
      the mechanism of DDC and EBDC enhancement of MPTP toxicity. Given the widespread
      use of these compounds in the environment such studies may also provide clues to
      the process of nigrostriatal cell degeneration in Parkinson's disease.

PMID- 10894121
TI  - Induction of cell death by L-alpha-aminoadipic acid exposure in cultured rat
      astrocytes: relationship to protein synthesis.
AB  - The excitotoxin, L-alpha-aminoadipic acid (L-AAA), kills primary astrocytes in
      the brain. The mechanism underlying the induction of cell death is not well
      understood although many possible mechanisms are theorized. Previous studies have
      reported that astrocytes die after prolonged exposure to L-AAA suggesting a
      delayed programmed cell death and apoptosis. In this study rat cortical
      astrocytes exposed to continuous 1 mM L-AAA exposure for 24-, 48-, or 72 hours
      demonstrated increased DNA laddering, a characteristic of apoptosis.
      Unexpectedly, this was not ameliorated by the presence of cycloheximide at 0.1
      microg/ml medium. Because of our interest in cytoprotective heat shock proteins
      induced by excitoxic stress, we studied the effect of prolonged exposure of L-AAA
      on the synthesis of stress proteins and protein synthesis in rat cortical
      astrocytes. Protein synthesis as measured by [35S]-methionine labeling showed a
      marked and significant decrease in incorporation of radiolabel after 24 hours of
      exposure to L-AAA and prior to induction of significant cell death noted at 48-
      and 72 hours of L-AAA exposure. The inhibition of protein synthesis was partially
      reversible at 24 hours if cells were labeled in medium without L-AAA during the
      radiolabeling period. Heat shock or stress proteins, HSP70 and heme oxygenase-1
      (HO-1), were analyzed after a 24 hour exposure to L-AAA and showed no significant
      induction of HSP70 or HO-1. The findings suggest that the prolonged inhibition of
      protein synthesis and associated lack of induction of HSP70 and HO-1 synthesis
      contributed to apoptotic cell death induced by the excitoxin L-AAA.

PMID- 10894122
TI  - Development and characterization of a rodent model of methanol-induced retinal
      and optic nerve toxicity.
AB  - Methanol is an important public health and environmental concern because of the
      selective actions of its neurotoxic metabolite, formic acid, on the retina, optic
      nerve and central nervous system. Humans and non-human primates are uniquely
      sensitive to methanol-induced neurotoxicity as a consequence of the limited
      capacity of primate species to oxidize and thus detoxify formic acid. The toxic
      syndrome in primates is characterized by formic acidemia, metabolic acidosis and
      blindness or serious visual impairment. Nonprimate species are normally resistant
      to the accumulation of formate and associated metabolic and visual toxicity. We
      have characterized retinal and optic nerve toxicity in a nonprimate model of
      methanol toxicity using rats in which folate-dependent formate oxidation has been
      selectively inhibited, allowing formate to accumulate to toxic concentrations
      following methanol administration. Methanol-intoxicated rats developed formic
      acidemia, metabolic acidosis and visual toxicity analogous to the human methanol
      poisoning syndrome. Visual dysfunction was manifested as reductions in the
      electroretinogram and the flash-evoked cortical potential which occurred
      coincident with blood formate accumulation. Histological studies revealed
      mitochondrial disruption and vacuolation in the retinal pigment epithelium,
      photoreceptor inner segments and optic nerve. The temporal relationship between
      methanol administration and the onset and development of ocular toxicity, as well
      as, the degree of metabolic acidosis and extent of formic acidemia in this rodent
      model are remarkably similar to that documented in human methanol intoxication.
      Moreover, the functional and morphologic findings in methanol-intoxicated rats
      are consistent with the hypothesis that formate acts as a mitochondrial toxin in
      the retina and optic nerve. The establishment and characterization of this
      nonprimate animal model of methanol intoxication will facilitate research into
      the mechanistic aspects of methanol toxicity and the development and testing of
      treatments for human methanol poisoning.

PMID- 10894123
TI  - Quantification of acute neurotoxic effects of trimethyltin using neuronal
      networks cultured on microelectrode arrays.
AB  - We used spontaneously active monolayer networks in vitro, cultured on thin film
      microelectrode arrays as experimental platforms for the determination of
      trimethyltin chloride (TMT) toxicity. Two different tissues of the mouse CNS
      (spinal cord and auditory cortex) exhibited characteristic and dose-dependent
      changes of their electrophysiological activity patterns after treatment with TMT,
      a standard neurotoxicant. Spinal cord networks began to respond to TMT at 1-2
      microM and shut off activity at 4-7 microM. Auditory cortex cultures started to
      respond at 2-3 microM and shut off activity at 7-8 microM. Repeated applications
      of low doses of TMT always influenced the electrical activity in a reversible
      manner, with no overt cytotoxic effects. The inhibitory concentrations for a 50%
      reduction of activity (IC ) were 1.5+/-0.5 microM (spinal cord) and 4.3+/-0.9
      microM (auditory cortex) indicating a relatively low interculture variability
      within one tissue type. The non-overlapping IC50 range for cortical and spinal
      cord cultures may suggest tissue specificity for network responses to TMT. Shut
      off concentrations were found to be within a factor of two of the lethal
      concentrations reported for mice in vivo. Action potential amplitude and shape
      did not change even when complete cessation of activity was approached,
      suggesting that acute TMT applications did not affect neuronal metabolism that
      would lead to a lowering of membrane potentials. Our results suggest that
      spontaneously active monolayer networks in vitro are suitable for toxicological
      investigations since network activity can be influenced in a dose-dependent
      manner. These properties allow the development of neurotoxicity biosensors based
      on physiological responses of spontaneously active networks.

PMID- 10894124
TI  - Effect of the pesticide Deltamethrin on the Mauthner cells of Lake Balaton fish.
AB  - Deltamethrin, a synthetic pesticide [(S)alpha-cyano-3-phenoxybenzyl-(1R)-cis-3
      (2.2-dibromovinyl)-2,2-dim ethylcyclopropane-carboxylate] used for extermination
      of mosquitoes on the shores of lake Balaton, has been found to induce severe
      impairments of the nervous system of several Lake Balaton fish, such as carp
      (Cyprinus carpio), goldfish (Carassius auratus gibelis Bloch), eel (Anguilla
      anguilla) and wels (Silurus glanis). It has been shown that Deltamethrin, in a
      concentration of 1 microgram/liter in the aquarium water, inhibits
      acetylcholinesterase enzyme activity of the giant Mauthner's nerve cells as well
      as of the axon terminals synapsing with these cells. Even more importantly,
      however, Deltamethrin in a concentration of 10 micrograms per liter, induces
      blockade of the expression of choline acetyltransferase in the bulbous axon
      terminals synapsing with the lateral dendrites of the Mauthner cells. Since,
      under normal conditions, the function of the Mauthner cells is to co-ordinate the
      C-start reaction, by which fish rapidly leave sites of nociceptive stimulation,
      it stands for reason to assume that Deltamethrin intoxicated fish may be prone to
      become victims of various factors which endanger survival of the individual.
      During the last decade, waves of fish deaths were observed in Lake Balaton, which
      is the largest fresh-water lake in Europe. Fish death coincided with airborne
      mosquito-killing campaigns. Results of the enzyme- and immunohistochemical
      studies described in this paper, together with the deleterious effects of
      Deltamethrin to the enteric nervous system of fish which has been reported
      earlier (Lang et al., 1997) suggest that fish death might be caused by the
      indiscriminate use of Deltamethrin airborne spray in the mosquito-extermination
      campaigns.

PMID- 10894125
TI  - Inorganic lead and calcium interact positively in activation of calmodulin.
AB  - Calmodulin is a ubiquitous calcium-binding protein that mediates many of the
      intracellular actions of Ca2+ ions. The calcium-binding sites of calmodulin
      consist of four EF-hand motifs; full activation of calmodulin normally occurs
      when all four sites are occupied by Ca2+. Inorganic lead (PY2+) has been shown to
      activate calmodulin at total lead concentrations similar to the concentrations of
      Ca2+ required for activation (Goldstein and Ar, 1983; Habermann et al., 1983),
      but the free Pb2+ concentrations required for calmodulin activation have not been
      determined. In addition, it is possible that activation may occur with different
      sites occupied by different divalent cations, for example Ca2+ and Pb2+. We
      investigated the ability of free Pb2+, alone or in combination with Ca2+, to
      activate calmodulin. In aqueous media, N-phenyl-1-naphthylamine (NPN) and 8
      anilino-1-naphthalenesulfonate (ANS) show increased fluorescence when bound to
      hydrophobic regions of proteins. This increased fluorescence has been used to
      monitor the conformational change that occurs during calmodulin activation
      (LaPorte et al., 1980). In the presence of calmodulin, both Ca2+ and Pb2+
      stimulated increased fluorescence of NPN and ANS. Threshold and EC50 free metal
      concentrations were approximately 100 nM and 450-500 nM, respectively, for Ca2+
      and 100 pM and 400-550 pM, respectively, for Pb2+. Fluorescence was enhanced by
      combinations of low concentrations of free Ca2+ and Pb2+; for example, as little
      as 20 pM free Pb2+ enhanced fluorescence in combination with 200 nM free Ca2+.
      The activity of the PDE1 isoform of cyclic nucleotide phosphodiesterase is
      stimulated by Ca2+/calmodulin (Wang et al., 1990). In the presence of calmodulin,
      we found that Ca2+ and Pb2+ activated calmodulin-stimulated PDE activity, with
      threshold and EC50 free metal concentrations of approximately 200 nM and 1200 nM,
      respectively, for Ca2+ and 300 pM and 430 pM, respectively, for Pb2+. PDE
      activity was stimulated by combinations of Ca2+ and Pb2+. For example, with 100
      nM free Ca2+, as little as 50 to 100 pM free Pb2+ further stimulated PDE
      activity; with 1000 nM free Ca2+, 20 to 50 pM free Pb2+ further stimulated PDE
      activity. Isobolographic analysis indicated that stimulation of PDE by Ca2+ and
      Pb2+ was additive. These results show that concentrations of free Pb2+ as low as
      100 to 300 pM activate calmodulin and that, in the presence of physiological
      concentrations of free Ca2+, Pb2+ can activate calmodulin at concentrations below
      50 pM. The intracellular free Ca2+ concentration in Ca2+ "hot spots," for example
      near sites of influx through Ca2+-permeable plasma membrane channels, can reach
      dozens of pM, with the free Ca2+ concentration decreasing rapidly with distance
      from the source of the hot spot. Our results suggest that picomolar
      concentrations of intracellular free Pb2+ should expand both the effective
      amplitude and volume of Ca2+ hot spots with respect to calmodulin activation, and
      thus may amplify intracellular Ca2+ signaling in lead-exposed cells.

PMID- 10894126
TI  - Nanomolar concentrations of inorganic lead increase Ca2+ efflux and decrease
      intracellular free Ca2+ ion concentrations in cultured rat hippocampal neurons by
      a calmodulin-dependent mechanism.
AB  - Inorganic lead (Pb2+) activates calmodulin, which in turn may stimulate many
      other cellular processes. The plasma membrane Ca2+ ATPase is a calmodulin
      stimulated enzyme that plays the major role in regulating the "resting"
      intracellular free Ca2+ ion concentration, [Ca2+]i. We hypothesized that exposing
      neurons to low levels of Pb2+ would cause Pb2+ to enter the cytoplasm, and that
      intracellular Pb2+, by activating calmodulin, would stimulate plasma membrane
      Ca2+ ATPase activity, thereby increasing Ca2+ extrusion and reducing [Ca2+]i. We
      used the ratiometric Ca2+ indicator fura-2 to estimate changes in [Ca2+]i. In
      vitro calibrations of fura-2 with solutions of defined free Ca2+ and free Pb2+
      concentrations showed that, at free Ca2+ concentrations from 10 nM to 1000 nM,
      adding Pb2+ caused either no significant change in the F340/F380 ratio (free Pb2+
      concentrations from 100 fM to 1 pM) or increased the F340/F380 ratio (free Pb2+
      concentrations from 5 to 50 pM). Therefore, fura-2 should be suitable for
      estimating Pb2+-induced decreases in [Ca2+]i, but not increases in [Ca2+]i. We
      exposed cultured embryonic rat hippocampal neurons to 100 nM Pb2+ for periods
      from 1 hour to 2 days and measured the F340/F380 ratio; the ratio decreased
      significantly by 9 to 16% at all time points, indicating that Pb2+ exposure
      decreased [Ca2+]i. In neurons loaded with 45Ca, Pb2+ exposure increased Ca2+
      efflux for at least two hours; by 24 hours, Ca2+ efflux returned to control
      levels. Influx of 45Ca was not altered by Pb2+ exposure. Low concentrations (250
      nM) of the calmodulin inhibitor calmidazolium had no effect on either 45Ca efflux
      or on the F340/F380 ratio in fura-loaded control neurons, but completely
      eliminated the increase in 45Ca efflux and decrease in F340/F380 ratio in Pb2+
      exposed neurons. Zaldoride, another calmodulin inhibitor, also eliminated the
      decrease in F340/F380 ratio in Pb2+-exposed neurons. We conclude that Pb2+
      exposure decreases [Ca2+]i and increases Ca2+ efflux in cultured hippocampal
      neurons by a calmodulin-dependent mechanism, probably by stimulating Ca2+
      extrusion by the plasma membrane Ca2+ ATPase.

PMID- 10894127
TI  - The interaction of lead exposure and arylsulfatase A genotype affects sulfatide
      catabolism in human fibroblasts.
AB  - Lead exposure causes cognitive and behavioral deficits in some affected children.
      We propose that a contributing mechanism for the neurological damage is that lead
      induces critically low levels of arylsulfatase A (ASA) at sensitive stages of
      nervous system development. It is hypothesized that the combined effects of a
      single nucleotide polymorphism (SNP) in human ASA which results in reduced levels
      of the enzyme, and lead concentrations which decrease ASA activity culminate in
      cellular enzymic activity that is below a critical threshold required for the
      maintenance of normal nervous system function. Human fibroblasts grown in the
      presence of 20 microM lead acetate exhibit a more than 60% decrease of cellular
      ASA enzyme protein. Lead treatment of cells from individuals with the SNP(s) of
      pseudodeficient ASA, but not those from subjects with the normal gene, results in
      a significant decrease in ability of the cells to desulfate sulfatide, the
      substrate of ASA. The decrease in the degree of sulfatide catabolism is
      consistent with possible enhanced lead-induced neurobehavioral effects in
      individuals homozygous for the pseudodeficiency polymorphism(s) of ASA.

PMID- 10894128
TI  - Distribution of paclitaxel within the nervous system of the rat after repeated
      intravenous administration.
AB  - The distribution of paclitaxel (Taxol) within the central and peripheral nervous
      system after repeated administration of this antineoplastic agent is still
      largely unknown. In this study we determined for the first time paclitaxel tissue
      concentration in the brain, spinal cord, dorsal root ganglia (DRG) and sciatic
      nerve using an experimental paradigm in the rat which reproduces the features of
      paclitaxel peripheral neurotoxicity in humans. Pathological confirmation of the
      onset of paclitaxel-induced peripheral neurotoxicity was performed. In order to
      achieve reliable results even with low concentrations of paclitaxel, a newly
      reported analytical method (high-performance liquid chromatography with tandem
      mass spectrometry) was used. We demonstrated that paclitaxel has easy access to
      the DRG, where it accumulates, while the lowest concentrations of the drug were
      measured in the brain. The intermediate concentrations of paclitaxel observed in
      the sciatic nerve and spinal cord may be due to paclitaxel transport along the
      centrifugal and centripetal branches of the DRG neuron axons.

PMID- 10894129
TI  - Preferential destruction of cerebellar Purkinje cells by OX7-saporin.
AB  - Saporin, a plant toxin derived from Saponaria officinalis, disrupts protein
      synthesis by inactivating the 60S portion of the ribosomal complex. OX7 is a
      mouse monoclonal antibody directed against the Thy-1.1 receptor that is
      differentially expressed on subpopulations of central nervous system neurons.
      Disulfide conjugation of OX7 to saporin permits delivery of saporin to target
      neurons. OX7-saporin was used to study the behavioral and morphological
      consequences of selective destruction of cerebellar Purkinje cells which
      abundantly express the Thy-1.1 antigen. Male Sprague-Dawley rats received
      bilateral intraventricular injections of 1- or 2 microg OX7-saporin or 8 microl
      artificial CSF. Rats were tested for behavioral changes 1 week before and 1, 2,
      and 8 weeks post-treatment. OX7-saporin treatment resulted in dose- and time
      dependent changes in motor performance, activity, and negative geotaxis, but did
      not affect foot splay. Following behavioral testing, cerebellar sections were
      prepared for microscopic examination and the pattern of Purkinje cell loss was
      determined in anatomically matched sections. OX7-saporin induced dose-dependent
      death of Purkinje cells, particularly in the anterior and superior portions of
      cerebellar folia 1-6 and folium 9. Other brain regions appeared largely
      unaffected. Data suggest that intraventricular injection of rats with OX7-saporin
      is an effective model with which to examine the consequences of Purkinje cell
      destruction.

PMID- 10894130
TI  - Diffusion-weighted magnetic resonance imaging in a case of methanol intoxication.
AB  - BACKGROUND: Methanol intoxication is an uncommon clinical problem leading to
      profound metabolic acidosis with serious neurological deterioration. We describe
      methanol induced brain lesions on diffusion-weighted MR images and discuss the
      pathophysiology of these lesions in light of diffusion changes. CASE REPORT:
      Brain imaging was performed in a 32 year-old man in a coma with focal
      neurological signs. Bilateral putaminal [hyperintensity] was seen on fast spin
      echo T2-weighted sequences, on Fluid Attenuated Inversion Recovery (FLAIR) and on
      diffusion weighted images. Decreased ADC values were observed bilaterally in the
      putamina. In addition, FLAIR images showed diffuse hypersignal in the
      subarachnoidal space. The patient showed rapid neurological deterioration while
      blood chemical tests revealed a severe metabolic acidosis and plasma methanol
      levels of 21 mmol/L. The patient died from hepatic failure thirty six hours after
      admission. CONCLUSION: Although decreased ADC values on diffusion-weighted
      imaging are commonly associated with arterial ischemic stroke, this pattern can
      also be observed in the case of putaminal necrosis following methanol ingestion.

PMID- 10894131
TI  - Neurotoxic interactions of industrially used ketones.
AB  - Occupationally workers are most often exposed to a mixture of solvents. Exposure
      limits are, however, usually set separately for single solvents. So we reviewed
      the present knowledge about possible neurotoxic interactions of the industrially
      most used ketones acetone (ACE), methyl ethyl ketone (MEK) and methyl isobutyl
      ketone (MIBK) with solvents in general. A literature search from the last 25
      years (1974-1998) revealed 54 original publications describing neurotoxic
      monitoring after combined exposure (experimental and occupational) involving the
      mentioned ketones. Animal exposure was described in 27 reports, exposure
      involving human volunteers in 12 reports, and occupational surveys constituted 15
      reports. Of the 54 papers, 25 dealt with potentiation by ACE, MEK or MIBK of n
      hexane or 2,5-hexanedione (2,5-HD) induced neurotoxicity. Possible synergistic
      interactions of the ketones were reported in 12 of the 29 remaining works. Only
      two studies reported neurotoxic potentiation after acute short-term combined
      exposure to human volunteers. Possible neurotoxic potentiation by the ketones
      after occupational mixed exposure without the involvement of n-hexane or 2,5-HD,
      were reported in 8 papers. Some studies reported a different outcome of metabolic
      interactions based on animal or volunteer exposure, compared to more long-term
      occupational exposure. We conclude that the widespread use of the rule of
      additivity often underestimates the effect when dealing with combined exposure to
      industrially used ketones. We also conclude that the results of combined exposure
      obtained in animals or human volunteers cannot necessarily be extrapolated to
      occupational situations. More research is needed in particular concerning the
      most frequently occurring mixtures comprising ketones and aromatic solvents such
      as acetone (ACE) and styrene as well as methyl isobutyl ketone (MIBK) and
      toluene.

PMID- 10894132
TI  - Drive-through mastectomy and breast reconstruction.

PMID- 10894133
TI  - The path to recurrence is paved with good intentions.

PMID- 10894134
TI  - Not all MRI techniques are created equal.

PMID- 10894135
TI  - Does sentinel lymphadenectomy improve staging and alter therapy in elderly women
      with breast cancer?
AB  - BACKGROUND: Routine axillary lymph node dissection (ALND) for elderly women with
      invasive breast cancer has been questioned because it rarely alters therapy yet
      carries a significant morbidity rate. Sentinel lymphadenectomy (SLND) improves
      axillary staging and alters therapy in women with T1 breast cancer, but it is not
      clear whether SLND alters therapy in elderly women with breast cancer. METHODS: A
      prospective breast cancer data base was used to identify women 70 years old and
      older who underwent SLND for axillary staging of invasive breast cancer between
      1991 and 1998. RESULTS: There were 75 invasive breast cancers in 73 women. The
      mean patient age was 74.5 years (range, 70-90 years). Median tumor size was 1.4
      cm (range, 0.1-6.2 cm). Of the 75 tumors, 42 (56%) had favorable primary
      characteristics; the remaining tumors had unfavorable characteristics. SLND was
      performed alone in 17 cases (23%) and was followed by completion ALND in 58 cases
      (77%). Positive lymph nodes were identified in 32 cases (43%); 26 (81.3%) were
      detected by hematoxylin and eosin stains, and 6 (18.7%) were detected by
      immunohistochemistry alone. Five patients (6.9%) received adjuvant chemotherapy.
      Seven patients (9.6%) received axillary/supraclavicular radiation for positive
      nodes. Ten (13.7%) of 73 patients had obvious alterations in therapy because of
      axillary nodal status. As a result of SLND, 3 (13.6%) of 22 patients with tumors
      1.0 cm or smaller received tamoxifen, and 7 (15%) of 46 patients with tumors
      between 1.0 and 3.0 cm in size had changes in therapy. When patient and tumor
      characteristics were analyzed to determine relationships to therapeutic decision
      making, nodal status was the variable most significantly associated with changes
      in therapy (P = .0001). CONCLUSIONS: SLND improves axillary staging in elderly
      women with invasive breast cancer. Results of immunohistochemistry do not alter
      therapy in this group of individuals (P = .6367). In patients with small primary
      tumors, SLND alters therapy by increasing the number of patients receiving
      tamoxifen. In addition, SLND affects adjuvant systemic chemotherapy and regional
      radiotherapy in a significant number of patients with larger tumors, particularly
      tumors between 1.0 and 3.0 cm.

PMID- 10894136
TI  - Magnetic resonance imaging facilitates breast conservation for occult breast
      cancer.
AB  - INTRODUCTION: Occult primary breast cancer, i.e., isolated axillary
      adenocarcinoma without detectable tumor in the breast by either physical exam or
      mammography, represents up to 1% of operable breast cancer. Modified radical
      mastectomy (MRM) is generally the accepted treatment for this condition although
      tumor is identified in only two-thirds of mastectomy specimens. Breast magnetic
      resonance imaging (MRI) can identify occult breast carcinoma and may direct
      therapy. This study examined the ability of breast MRI to detect occult breast
      cancer and to facilitate breast conservation therapy. METHODS: Forty women with
      biopsy-proven metastatic adenocarcinoma to an axillary lymph node and no evidence
      of primary cancer were studied. All patients had a physical examination,
      mammography, and MRI of the breast. Using a dedicated breast coil, MRI imaging
      was performed with and without gadolinium enhancement. Positive MRI scans were
      compared with histopathologic findings at the time of operation (n = 21).
      RESULTS: MRI identified the primary breast lesion in 28 of 40 women (70%). Of
      these 28 patients, 11 had MRM, 11 had lumpectomy/axillary lymph node dissection
      (ALND)/radiotherapy (XRT), 2 had ALND/XRT alone, and 4 had no local treatment
      secondary to stage IV disease. Two women initially treated with lumpectomy/ALND
      subsequently had mastectomy for positive margins. Of the women with positive MRI
      who had breast surgery, 21 of 22 (95%) had tumor within the surgical specimen.
      Twelve women had negative MRI of the breast. Five of these 12 underwent MRM, of
      whom 4 had no tumor in the mastectomy specimen. The remaining 7 patients had ALND
      and whole breast radiation (ALND/XRT) (n = 5), or were observed (n = 2). Overall,
      18 of 34 women surgically treated had MRM, while 16 (47%) preserved their breast.
      Tumor yield for patients having breast surgery was 81%. CONCLUSIONS: MRI of the
      breast can identify occult breast cancer in many patients and may facilitate
      breast conservation in select women. Negative breast MRI predicts low tumor yield
      at mastectomy.

PMID- 10894137
TI  - Factors affecting distant disease-free survival for primary invasive breast
      cancer: use of a log-normal survival model.
AB  - BACKGROUND: Invasive breast cancer is a frequently diagnosed disease that now
      comes with an ever expanding array of therapeutic management options. We assessed
      the effects of 20 prognostic factors in a multivariate context. METHODS: We
      accrued clinical data for 156 consecutive patients with stage 1-3 primary
      invasive breast cancer who were diagnosed in 1989-1990 at the Henrietta Banting
      Breast Center, and followed to 1995. There is complete follow-up for 91% of
      patients (median follow-up of 4.9 years). The event of interest was distant
      recurrence (for distant disease-free survival, DFS). We used Cox and log-normal
      step-wise regression to assess the multivariate effects of the following factors
      on DFS: age, tumor size, nodal status, histology, tumor and nuclear grade,
      lymphovascular and perineural invasion (LVPI), ductal carcinoma-in-situ (DCIS)
      type, DCIS extent, DCIS at edge of tumor, ER and PgR, ERICA, adjuvant systemic
      therapy, ki67, S-phase, DNA index, neu oncogene, and pRb. RESULTS: There was
      strong evidence against the Cox assumption of proportional hazards for nodal
      status, and nodal status was not in the Cox step-wise model. With step-wise log
      normal regression, a large tumor size (P < .001), positive nodes (P = .002), high
      nuclear grade (P = .01), presence of LVPI (P = .03), and infiltrating duct
      carcinoma not otherwise specified (P = .05) were associated with a reduction in
      DFS. CONCLUSIONS: For nodal status, there was strong evidence against the Cox
      assumption of proportional hazards, and it was not included in the Cox model
      although it was in the log-normal model. Only traditional factors were included
      in the step-wise models. Thus, this statistical management of prognostic markers
      in breast cancer appears to be very important.

PMID- 10894138
TI  - The effects of type of surgery and time on psychological adjustment in women
      after breast cancer treatment.
AB  - BACKGROUND: The aim of the present study was to examine whether type of surgery,
      age, and time since surgery influenced psychological distress and quality of life
      (QOL) in women treated for breast cancer. METHODS: We surveyed 183 women who had
      undergone surgery for breast cancer. Psychological distress was measured with the
      Mental Health Inventory and QOL was measured with the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire. RESULTS: After
      controlling for stage of disease, radiation treatment, and age, there was a
      statistically significant interaction between type of surgery and time since
      surgery for the Mental Health Inventory total score, and a marginal interaction
      between type of surgery and time since surgery for the Global health status/QOL
      score. Women who had breast conservation surgery experienced significantly
      greater levels of psychological distress and marginally worse QOL from 40 months
      after surgery onward than did women who received a mastectomy. CONCLUSIONS: The
      effects of different surgical treatments for breast cancer on psychological
      distress and QOL become apparent only after a period of several years. Women,
      therefore, need counseling on the potentially positive and negative psychological
      implications of different surgical treatments for breast cancer.

PMID- 10894139
TI  - Prognostic implications of pathological lymph node status after preoperative
      chemotherapy for operable T3N0M0 breast cancer.
AB  - BACKGROUND: Although preoperative chemotherapy has become the standard of care
      for inoperable locally advanced breast cancer, its role for downstaging
      resectable primary tumors is still evolving. The purpose of this study was to
      determine whether the prognostic information from an axillary node dissection in
      patients with clinical T3N0 breast cancer was altered by preoperative
      chemotherapy compared with surgery de novo. METHODS: Between 1976 and 1994, 91
      patients with clinically node-negative operable T3 breast cancer received
      doxorubicin-based combination chemotherapy on protocol at one institution. Fifty
      three patients received both preoperative and postoperative chemotherapy
      (PreopCT), and 38 received postoperative chemotherapy only (PostopCT). All
      patients underwent axillary lymph node dissection as part of their definitive
      surgical treatment. There were no differences between the PreopCT and PostopCT
      groups in median age (51 vs. 49 years), median tumor size at presentation (6 cm
      vs. 6 cm), tumor grade, or estrogen receptor status (estrogen receptor negative
      38% vs. 32%). The median follow-up time was 7 years. RESULTS: Patients in the
      PreopCT group had fewer histologically positive lymph nodes (median, 0 vs. 3, P <
      .01), and a lower incidence of extranodal extension (19% vs. 42%, P = .02). By
      univariate analysis, the number of pathologically positive lymph nodes (P < .01)
      and extranodal extension (P < .01) were predictors of disease-specific survival
      in PreopCT patients. Multivariate analysis showed that extranodal extension was
      the only independent prognostic factor in PreopCT patients (P < .01). Overall,
      PreopCT and PostopCT patients had similar 5-year disease-free survival rates (66%
      vs. 57%); however, PreopCT patients had worse disease-free (P = .01) and disease
      specific survival (P = .04) when survival was compared after adjustment for the
      number of positive lymph nodes. Furthermore, PreopCT patients with 4-9 positive
      lymph nodes had a lower 5-year disease-free survival rate than PostopCT patients
      with 4-9 positive nodes (17 vs. 48%, P = .04). CONCLUSIONS: Axillary lymph node
      status remains prognostic after chemotherapy. Pathologically positive lymph nodes
      after preoperative chemotherapy are associated with a worse prognosis than the
      same nodal status before chemotherapy.

PMID- 10894140
TI  - Transcutaneously tunneled central venous lines in cancer patients: an analysis of
      device-related morbidity factors based on prospective data collection.
AB  - BACKGROUND: Long-term transcutaneous tunneled central venous catheters are
      frequently placed in cancer patients, accounting for significant costs and
      morbidity. Factors influencing outcome, though, are poorly studied. METHODS:
      Between June 1991 and June 1993, 923 central venous tunneled catheters were
      placed in 791 patients at Memorial Sloan-Kettering Cancer Center. Placement-,
      device-, and patient-related parameters were charted prospectively (median follow
      up: 120 days) and correlated to device-specific outcome events. RESULTS: Median
      patient age was 28.5 years (range: 0.025 - 84.5). Disease distribution included
      hematologic malignancies (64.7%), solid tumors (30.4%), and others (4.9%).
      Primary indications for line access included chemotherapy (72.8%), bone marrow
      transplantation (18.7%), total parenteral nutrition (6.4%), and drug
      administration (2.1%). There were 11 insertion complications (1.2%), including
      insertion failure (n = 6), hemorrhage (n = 4), and malposition (n = 1).
      Subsequent to placement, a proven or suspected device-specific complication
      occurred in 540 lines (58.5%). Per 10,000 catheter days, there were 17.6
      infection episodes, 8.1 thrombotic complications, 6.9 instances of catheter
      breakage, 3.5 accidental or inadvertent cases of displacement, and 0.6 device
      leaks. Reasons for line removal or other termination of follow-up were patient's
      death (32.1%), treatment end (28%), infection (19.6%), suspected infection
      (6.3%), displacement (6.8%), thrombosis (3.1%), leak (1%), and others (3.1%).
      Median device-specific duration was 365 days, compared with a median complication
      free device-specific duration of 167 days (P < 0.0001), reflecting a highly
      significant device salvage rate after complications. Catheter tip position
      emerged as the dominant independent prognostic factor for reduced device-specific
      duration or complication-free device-specific duration. CONCLUSIONS:
      Transcutaneous tunneled central venous lines can be placed safely, with a
      considerable incidence of subsequent device-specific complications, but a high
      salvage rate. Factors determining outcome are related to device placement, as
      well as the patient's disease status. In this study, patients alive 90 days after
      catheter placement had a 37% chance for a device complication, with a 20% chance
      for device loss. Future analyses of intermediate-term intravenous access should
      employ the measurement of device-specific outcome as a reference parameter to
      assess clinical results.

PMID- 10894141
TI  - Sentinel node staging for cutaneous melanoma in a university-affiliated community
      care setting.
AB  - BACKGROUND: The feasibility of intraoperative lymphatic mapping and sentinel
      lymphadenectomy (SLND) in settings other than high-volume specialized clinics has
      been questioned. We sought to determine the feasibility of SLND in a university
      affiliated private teaching hospital. METHODS: A multidisciplinary sentinel node
      program was established to include surgeons, nuclear medicine physicians, and
      pathologists. Within this program, 79 patients with cutaneous melanoma underwent
      attempted SLND after cutaneous lymphoscintigraphy (CL), between January 1994 and
      December 1998. All sentinel nodes were examined by hematoxylin-eosin staining and
      determined whether negative for evidence metastatic disease by both S-100 and HMB
      45 immunohistochemical staining. RESULTS: CL was successful in 77 (97%) of 79
      patients. A total of 88 lymphatic basins were found to be at risk for metastatic
      disease by CL. SLND was not successful in the two patients who did not have a
      successful CL. Sentinel nodes were identified in all but three patients with the
      remaining 88 lymphatic basins (technical success, 97%). There was one false
      negative in this group of patients (approximately 1%). CONCLUSIONS: SLND is a
      highly accurate way of staging the regional node basin. Our technical success
      rates and false-negative rates indicate the feasibility of this approach in
      settings other than high-volume specialty clinics.

PMID- 10894142
TI  - Thin < or = 1 mm level III and IV melanomas are higher risk lesions for regional
      failure and warrant sentinel lymph node biopsy.
AB  - BACKGROUND: Thin melanomas have become increasingly prevalent, and lesions 1 mm
      or less in thickness are frequently diagnosed. They are considered highly curable
      when treated with wide local excision alone with reported 5-year disease free
      survivals of 95% to 98%. However, thin Clark level III and IV melanomas may have
      an increased potential for metastasizing and late recurrence because of dermal
      lymphatics located at the interface of the papillary and reticular dermis. We
      have addressed this controversial area by reviewing the outcomes of patients with
      invasive thin (< or = 1.0 mm thick) melanomas. METHODS: We reviewed 415 invasive
      melanomas from 1983-1995 in the Rhode Island tumor registries which kept records
      of both tumor thickness and Clark levels. Sixty-eight (16.4%) of the 415 invasive
      melanomas were thin (< or = 1.0 mm in thickness) and were treated by wide local
      excision only. In situ lesions were excluded. Thirty-eight (56%) of the 68 thin
      melanomas were either Clark level III or IV. RESULTS: Seven (18.4%) of the 38
      level III and IV thin melanomas had a recurrence at a minimum follow-up of 36
      months. Median time to recurrence was 52 months, and the average measured depth
      of tumor thickness was 0.84 mm. Only one (3.3%) of 30 level II melanomas recurred
      (P < .05). CONCLUSIONS: Thin level III and IV melanomas are at increased risk for
      late recurrence when compared with all thin melanomas. Because there is effective
      adjuvant therapy with alpha interferon for patients with stage III melanoma to
      treat regional and systemic disease, and because sentinel lymph node biopsy
      (SLNB) offers minimal morbidity, we suggest using SLNB to accurately stage and
      treat all patients with thin melanoma that are high Clark levels that are at
      increased risk for metastases.

PMID- 10894143
TI  - Reliability of the sentinel node procedure in melanoma patients: analysis of
      failures after long-term follow-up.
AB  - BACKGROUND: The sentinel node (SN) concept assumes that early lymphatic
      metastases, if present, always are found first in the SN. The aim of this study
      was to determine the reliability of this procedure by establishing the success
      rate and number of failed procedures during a follow-up period of at least 2
      years. METHODS: From August 1993 to November 1996, 204 consecutive patients with
      stage I and II cutaneous melanoma underwent SN biopsy by a triple technique.
      Preoperatively, all patients underwent (dynamic) lymphoscintigraphy. A gamma
      probe and blue dye helped localize the SN(s) during surgery, and these nodes
      subsequently were excised. These lymph nodes were step-sectioned and examined by
      routine and immunohistochemical staining. If the SN contained tumor cells, a
      lymphadenectomy was performed at a later date. RESULTS: The median follow-up time
      was 42 months. The success rate was 99%. Three patients developed a recurrence in
      the negative SN basin during follow-up, without simultaneous appearance of
      (locoregional) metastases. CONCLUSIONS: With a 99% success rate and a 1.5% rate
      of failed SN procedures (7% false-negative rate) after a median follow-up of 3.5
      years, we concluded that the combined triple technique approach of detecting the
      SN was a reliable method to accurately identify and retrieve the SN.

PMID- 10894144
TI  - Sentinel lymph node biopsy in cutaneous melanoma: the WHO Melanoma Program
      experience.
AB  - BACKGROUND: We report the experience of the World Health Organization (WHO)
      Melanoma Program concerning sentinel lymph node (SLN) biopsy for detecting
      patients with occult regional nodal metastases to submit to selective regional
      node dissection. METHODS: From February 1994 to August 1998, in 12 centers of the
      WHO Melanoma Program, 892 SLN biopsies were performed in 829 patients with
      clinical stage I melanoma (male: 370; female: 459; median age: 50 years old). The
      location of the primary melanoma was as follows: trunk 35%; lower limbs, 45%;
      upper limbs, 18%; and head and neck, 2%. Blue dye injection for SLN
      identification was performed in all cases; preoperative lymphoscintigraphy was
      done in 440 patients, and an intra-operative probe for a radio-guided biopsy was
      used in 141 cases. Overall, the SLN identification rate was 88%. In 68% of the
      patients, only one SLN was identified, whereas two and three or more SLN were
      detected in 24% and 8% of the remaining cases, respectively. RESULTS: Overall SLN
      positivity rate was 18%. Intra-operative frozen section examination was performed
      in 39% of the cases and was helpful in detecting occult localizations only in 47%
      of the positive SLNs. Distribution of positive cases by primary thickness was as
      follows: < 1mm: 2%; 1-1.99 mm: 7%; 2-2.99 mm: 13%; and > or = 3 mm: 31%. Positive
      nonsentinel lymph nodes were found in 22% of cases with positive SLN submitted
      for selective dissection. No complications due to the procedure were registered.
      Of 710 patients who were evaluated, 40 (6%) presented a regional nodal relapse
      after a negative SLN biopsy and underwent a delayed therapeutic dissection. From
      the 710 enrolled cases, 638 (88.5%) were alive without evidence of disease at the
      time of this writing. A multivariate analysis showed SLN status as one of the
      most significant prognostic factors (P = .000) along with thickness (P = .001)
      and ulceration (P = .015) of primary tumor. CONCLUSIONS: These data confirm the
      feasibility and safety of the SLN technique for selecting patients to submit to a
      radical node dissection. The data represent the basis for a future trial by the
      WHO Melanoma Program in this field to evaluate the most appropriate surgical
      approach for treating patients with occult regional nodal metastases.

PMID- 10894145
TI  - Molecular chaperone interactions with steroid receptors: an update.

PMID- 10894146
TI  - Thyroid hormone regulation of hepatic genes in vivo detected by complementary DNA
      microarray.
AB  - The liver is an important target organ of thyroid hormone. However, only a
      limited number of hepatic target genes have been identified, and little is known
      about the pattern of their regulation by thyroid hormone. We used a quantitative
      fluorescent cDNA microarray to identify novel hepatic genes regulated by thyroid
      hormone. Fluorescent-labeled cDNA prepared from hepatic RNA of T3-treated and
      hypothyroid mice was hybridized to a cDNA microarray, representing 2225 different
      mouse genes, followed by computer analysis to compare relative changes in gene
      expression. Fifty five genes, 45 not previously known to be thyroid hormone
      responsive genes, were found to be regulated by thyroid hormone. Among them, 14
      were positively regulated by thyroid hormone, and unexpectedly, 41 were
      negatively regulated. The expression of 8 of these genes was confirmed by
      Northern blot analyses. Thyroid hormone affected gene expression for a diverse
      range of cellular pathways and functions, including gluconeogenesis, lipogenesis,
      insulin signaling, adenylate cyclase signaling, cell proliferation, and
      apoptosis. This is the first application of the microarray technique to study
      hormonal regulation of gene expression in vivo and should prove to be a powerful
      tool for future studies of hormone and drug action.

PMID- 10894147
TI  - Characterization of transiently and constitutively expressed progesterone
      receptors: evidence for two functional states.
AB  - Activated steroid receptors induce chromatin remodeling events in the promoters
      of some target genes. We previously reported that transiently expressed
      progesterone receptor (PR) cannot activate mouse mammary tumor virus (MMTV)
      promoter when it adopts the form of ordered chromatin. However, when expressed
      continuously, the PR acquires this ability. In this study we explored whether
      this gain of function occurs through alterations in nucleoprotein structure at
      the MMTV promoter or through changes in receptor status. We observed no major
      structural differences at the MMTV promoter in the presence of constitutively
      expressed PR and found its mechanism of activation to be very similar to that of
      the glucocorticoid receptor (GR). However, a systematic comparison of the
      functional behavior of the transiently and constitutively expressed PR elucidated
      significant differences. The transiently expressed PR is activated in the absence
      of ligand by cAMP and by components in FBS and has significantly increased
      sensitivity to progestins. In contrast, the constitutively expressed PR is
      refractory to activation by cAMP and serum and has normal sensitivity to its
      ligand. In addition, while the PR is localized to the nucleus in both cases, a
      significant fraction of the transiently expressed PR is tightly bound to the
      nucleus even in the absence of ligand, while the majority of constitutively
      expressed PR is not. These results strongly suggest that the PR undergoes
      processing in the cell subsequent to its initial expression and that this
      processing is important for various aspects of its function, including its
      ability to productively interact with target genes that require chromatin
      remodeling for activation.

PMID- 10894148
TI  - Sp1 binding sites and an estrogen response element half-site are involved in
      regulation of the human progesterone receptor A promoter.
AB  - Progesterone receptor gene expression is induced by estrogen in MCF-7 human
      breast cancer cells. Although it is generally thought that estrogen
      responsiveness is mediated through estrogen response elements (EREs), the
      progesterone receptor gene lacks an identifiable ERE. The progesterone receptor A
      promoter does, however, contain a half-ERE/Sp1 binding site comprised of an ERE
      half-site upstream of two Sp1 binding sites. We have used in vivo
      deoxyribonuclease I (DNase I) footprinting to demonstrate that the half-ERE/Sp1
      binding site is more protected when MCF-7 cells are treated with estrogen than
      when cells are not exposed to hormone, suggesting that this region is involved in
      estrogen-regulated gene expression. The ability of the half-ERE/Sp1 binding site
      to confer estrogen responsiveness to a simple heterologous promoter was confirmed
      in transient cotransfection assays. In vitro DNase I footprinting and gel
      mobility shift assays demonstrated that Sp1 present in MCF-7 nuclear extracts and
      purified Sp1 protein bound to the two Sp1 sites and that the estrogen receptor
      enhanced Sp1 binding. In addition to its effects on Sp1 binding, the estrogen
      receptor also bound directly to the ERE half-site. Taken together, these findings
      suggest that the estrogen receptor and Sp1 play a role in activation of the human
      progesterone receptor A promoter.

PMID- 10894149
TI  - PNRC: a proline-rich nuclear receptor coregulatory protein that modulates
      transcriptional activation of multiple nuclear receptors including orphan
      receptors SF1 (steroidogenic factor 1) and ERRalpha1 (estrogen related receptor
      alpha-1).
AB  - PNRC (proline-rich nuclear receptor coregulatory protein) was identified using
      bovine SF1 (steroidogenic factor 1) as the bait in a yeast two-hybrid screening
      of a human mammary gland cDNA expression library. PNRC is unique in that it has a
      molecular mass of 35 kDa, significantly smaller than most of the coregulatory
      proteins reported so far, and it is proline-rich. PNRC's nuclear localization was
      demonstrated by immunofluorescence and Western blot analyses. In the yeast two
      hybrid assays, PNRC interacted with the orphan receptors SF1 and ERRalpha1 in a
      ligand-independent manner. PNRC was also found to interact with the ligand
      binding domains of all the nuclear receptors tested including estrogen receptor
      (ER), androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor
      (PR), thyroid hormone receptor (TR), retinoic acid receptor (RAR), and retinoid X
      receptor (RXR) in a ligand-dependent manner. Functional AF2 domain is required
      for nuclear receptors to bind to PNRC. Furthermore, in vitro glutathione-S
      transferase pull-down assay was performed to demonstrate a direct contact between
      PNRC and nuclear receptors such as SF1. Coimmunoprecipitation experiment using
      Hela cells that express PNRC and ER was performed to confirm the interaction of
      PNRC and nuclear receptors in vivo in a ligand-dependent manner. PNRC was found
      to function as a coactivator to enhance the transcriptional activation mediated
      by SF1, ERR1 (estrogen related receptor alpha-1), PR, and TR. By examining a
      series of deletion mutants of PNRC using the yeast two-hybrid assay, a 23-amino
      acid (aa) sequence in the carboxy-terminal region, aa 278-300, was shown to be
      critical and sufficient for the interaction with nuclear receptors. This region
      is proline rich and contains a SH3-binding motif, S-D-P-P-S-P-S. Results from the
      mutagenesis study demonstrated that the two conserved proline (P) residues in
      this motif are crucial for PNRC to interact with the nuclear receptors. The exact
      23-amino acid sequence was also found in another protein isolated from the same
      yeast two-hybrid screening study. These two proteins belong to a new family of
      nuclear receptor coregulatory proteins.

PMID- 10894150
TI  - Unliganded and liganded estrogen receptors protect against cancer invasion via
      different mechanisms.
AB  - While estrogens are mitogenic in breast cancer cells, the presence of estrogen
      receptor a (ERalpha) clinically indicates a favorable prognosis in breast
      carcinoma. To improve our understanding of ERalpha action in breast cancer, we
      used an original in vitro method, which combines transient transfection and
      Matrigel invasion assays to examine its effects on cell invasiveness. ERalpha
      expression in MDA-MB-231 breast cancer cells reduced their invasiveness by 3-fold
      in the absence of hormone and by 7-fold in its presence. Integrity of hormone and
      DNA-binding domains and activating function 2 were required for estradiol-induced
      inhibition, suggesting that transcriptional activation of estrogen target genes
      was involved. In contrast, these domains were dispensable for hormone-independent
      inhibition. Analysis of deletion mutants of ERalpha indicated that amino acids
      179-215, containing the N-terminal zinc finger of the DNA-binding domain, were
      required for ligand-independent receptor action. Among different members of the
      nuclear receptor family, only unliganded ERalpha and ERbeta reduced invasion.
      Calreticulin, a Ca2+-binding protein that could interact with amino acids 206-211
      of ERalpha, reversed hormone-independent ERalpha inhibition of invasion. However,
      since calreticulin alone also inhibited invasion, we propose that this protein
      probably prevents ERalpha interaction with another unidentified invasion
      regulating factor. The inhibitor role of the unliganded ER was also suggested in
      three ERalpha-positive cell lines, where ERalpha content was inversely correlated
      with cell migration. We conclude that ERalpha protects against cancer invasion in
      its unliganded form, probably by protein-protein interactions with the N-terminal
      zinc finger region, and after hormone binding by activation of specific gene
      transcription.

PMID- 10894151
TI  - Properties of the glucocorticoid modulatory element binding proteins GMEB-1 and 
      2: potential new modifiers of glucocorticoid receptor transactivation and members
      of the family of KDWK proteins.
AB  - An important component of glucocorticoid steroid induction of tyrosine
      aminotransferase (TAT) gene expression is the glucocorticoid modulatory element
      (GME), which is located at -3.6 kb of the rat TAT gene. The GME both mediates a
      greater sensitivity to hormone, due to a left shift in the dose-response curve of
      agonists, and increases the partial agonist activity of antiglucocorticoids.
      These properties of the GME are intimately related to the binding of a
      heteromeric complex of two proteins (GMEB-1 and -2). We previously cloned the rat
      GMEB-2 as a 67-kDa protein. We now report the cloning of the other member of the
      GME binding complex, the 88-kDa human GMEB-1, and various properties of both
      proteins. GMEB-1 and -2 each possess an intrinsic transactivation activity in
      mammalian one-hybrid assays, consistent with our proposed model in which they
      modify glucocorticoid receptor (GR)-regulated gene induction. This hypothesis is
      supported by interactions between GR and both GMEB-1 and -2 in mammalian two
      hybrid and in pull-down assays. Furthermore, overexpression of GMEB-1 and -2,
      either alone or in combination, results in a reversible right shift in the dose
      response curve, and decreased agonist activity of antisteroids, as expected from
      the squelching of other limiting factors. Additional mechanistic details that are
      compatible with the model of GME action are suggested by the interactions in a
      two-hybrid assay of both GMEBs with CREB-binding protein (CBP) and the absence of
      histone acetyl transferase (HAT) activity in both proteins. GMEB-1 and -2 share a
      sequence of 90 amino acids that is 80% identical. This region also displays
      homology to several other proteins containing a core sequence of KDWK. Thus, the
      GMEBs may be members of a new family of factors with interesting transcriptional
      properties.

PMID- 10894152
TI  - Residues in the ligand binding domain that confer progestin or glucocorticoid
      specificity and modulate the receptor transactivation capacity.
AB  - To localize regions conferring ligand binding specificity of the human
      glucocorticoid (hGR) and progesterone (hPR) receptors, we constructed chimeras
      comprising the DNA-binding domain of the yeast transcription factor GAL4, linked
      to the ligand binding domain of hGR or hPR. Replacement of a sequence of hGR
      encompassing helices H6 and H7 with the homologous sequence from hPR creates a
      chimeric protein GP3, which binds the progestin RU 27987 with high affinity, and
      results in a concomitant loss of glucocorticoid binding [dexamethasone (DEX), RU
      43044]. Moreover, GP3 is not able to mediate RU 27987-induced transactivation. A
      detailed mutational analysis of this sequence and the study of the recently
      solved hPR crystal structure revealed five residues that confer progestin
      responsiveness to GR or modulate ligand binding and transcriptional activation.
      Notably, the simultaneous presence of residues Ser637 and Phe639 on GP3, lining
      the ligand binding pocket, is specifically involved in RU 27987 binding. The
      absence of residues Asp641, Gln642, and Leu647 on GP3 is accountable for the lack
      of glucocorticoids binding on GP3. Unlike residue 642, residues 641 and 647 are
      not in direct contact with the ligand and most likely act through steric-mediated
      interactions. The presence of Gln642 and Leu647 are determinant for
      transcriptional activation in response to DEX and RU 27987, respectively. DEX
      dependent transactivation is further enhanced by the presence of Leu647.

PMID- 10894153
TI  - Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during
      embryogenesis.
AB  - Restricted germ cell loss through apoptosis is initiated in the fetal gonad
      around embryonic day 13.5 (E13.5) as part of normal germ cell development. The
      mechanism of this germ cell attrition is unknown. We show that Bcl-x plays a
      crucial role in maintaining the survival of mouse germ cells during
      gonadogenesis. A bcl-x hypomorphic mouse was generated through the introduction
      of a neomycin (neo) gene into the promoter of the bcl-x gene by homologous
      recombination. Mice that contained two copies of the hypomorphic allele had
      severe reproductive defects attributed to compromised germ cell development.
      Males with two mutant alleles lacked spermatogonia and were sterile; females
      showed a severely reduced population of primordial and primary follicles and
      exhibited greatly impaired fertility. Primordial germ cells (PGCs) in bcl-x
      hypomorph mice migrated to the genital ridge by E12.5 but were depleted by E15.5,
      a time when Bcl-x and Bax were present. Two additional bcl-x transcripts were
      identified in fetal germ cells more than 300 bp upstream of previously reported
      start sites. Insertion of a neo cassette led to a down-regulation of the bcl-x
      gene at E12.5 in the hypomorph. Bax was detected by immunohistochemistry in germ
      cells from bcl-x hypomorph and control testes at E12.5 and E13.5. Bcl-x function
      was restored, and animals of both genders were fertile after removal of the neo
      selection cassette using Cre-mediated recombination. Alternatively, the loss of
      Bcl-x function in the hypomorph was corrected by the deletion of both copies of
      the bax gene, resulting in a restoration of germ cell survival. These findings
      demonstrate that the balance of Bcl-x and Bax control PGC survival and apoptosis.

PMID- 10894154
TI  - Requirement of Bmp8b for the generation of primordial germ cells in the mouse.
AB  - In the mouse embryo, the generation of primordial germ cells (PGCs) from the
      epiblast requires a bone morphogenetic protein-4 (BMP4) signal from the adjacent
      extraembryonic ectoderm. In this study, we report that Bmp8b, a member of the Gbb
      60A class of the BMP superfamily, is expressed in the extraembryonic ectoderm in
      pregastrula and gastrula stage mouse embryos and is required for PGC generation.
      A mutation in Bmp8b on a mixed genetic background results in the absence of PGCs
      in 43% null mutant embryos and severe reduction in PGC number in the remainder.
      The heterozygotes are unaffected. On a largely C57BL/6 background, Bmp8b null
      mutants completely lack PGCs, and Bmp8b heterozygotes have a reduced number of
      PGCs. In addition, Bmp8b homozygous null embryos on both genetic backgrounds have
      a short allantois, and this organ is missing in some more severe mutants. Since
      Bmp4 heterozygote embryos have reduced numbers of PGCs, we used a genetic
      approach to generate double-mutant embryos to study interactions of Bmp8b and
      Bmp4. Embryos that are double heterozygotes for the Bmp8b and Bmp4 mutations have
      similar defects in PGC number as Bmp4 heterozygotes, indicating that the effects
      of the two BMPs are not additive. These findings suggest that BMP4 and BMP8B
      function as heterodimers and homodimers in PGC specification in the mouse.

PMID- 10894155
TI  - Identification of an ovarian voltage-activated Na+-channel type: hints to
      involvement in luteolysis.
AB  - An endocrine type of voltage-activated sodium channel (eNaCh) was identified in
      the human ovary and human luteinized granulosa cells (GC). Whole-cell patch-clamp
      studies showed that the eNaCh in GC is functional and tetrodotoxin (TTX)
      sensitive. The luteotrophic hormone human CG (hCG) was found to decrease the peak
      amplitude of the sodium current within seconds. Treatment with hCG for 24-48 h
      suppressed not only eNaCh mRNA levels, but also mean Na+ peak currents and
      resting membrane potentials. An unexpected role for eNaChs in regulating cell
      morphology and function was indicated after pharmacological modulation of
      presumed eNaCh steady-state activity in GC cultures for 24-48 h using TTX (NaCh
      blocker) and veratridine (NaCh activator). TTX preserved a highly differentiated
      cellular phenotype. Veratridine not only increased the number of secondary
      lysosomes but also led to a significantly reduced progesterone production.
      Importantly, endocrine cells of the nonhuman primate corpus luteum (CL), which
      represent in vivo counterparts of luteinized GC, also contain eNaCh mRNA.
      Although the mechanism of channel activity under physiological conditions is not
      clear, it may include persistent Na+ currents. As observed in GC in culture,
      abundant secondary lysosomes were particularly evident in the regressing CL,
      suggesting a functional link between eNaCh activity and this form of cellular
      regression in vivo. Our results identify eNaCh in ovarian endocrine cells and
      demonstrate that their expression is under the inhibitory control of hCG.
      Activation of eNaChs in luteal cells, due to loss of gonadotropin support, may
      initiate a cascade of events leading to decreased CL function, a process that
      involves lysosomal activation and autophagy. These results imply that ovarian
      eNaChs are involved in the physiological demise of the temporary endocrine organ
      CL in the primate ovary during the menstrual cycle. Because commonly used drugs,
      including phenytoin, target NaChs, these results may be of clinical relevance.

PMID- 10894157
TI  - Epidermal growth factor activates reproductive behavior independent of ovarian
      steroids in female rodents.
AB  - Sex steroids exert profound influence on neural development and function through
      activation of intranuclear receptors. However, during sexual differentiation and
      at onset of puberty, intracerebral estrogen (E) availability is subsequent to
      these effects. The potent mitogen epidermal growth factor (EGF) activates
      estrogen receptor (ER)-dependent transcription in cultured cells in the absence
      of exogenous E. Since reproductive behavior in female rodents is the result of E
      dependent transcriptional activity and protein synthesis, lordosis serves as a
      well established in vivo model for probing cellular and molecular mechanisms of
      steroid receptor-dependent behavior. Here we demonstrate that EGF can signal
      through the classical E receptor (ERalpha) to alter in vivo function in rodent
      central nervous system. EGF and EGF receptor ligands induced lordosis in a dose-
      and time-dependent manner in the absence of steroid treatment in ovariectomized
      rats and mice. Using antisense oligonucleotides, pharmacological and antibody
      blockade, and mutant mice, we also report that this behavioral responsiveness is
      mediated through ERalpha by specific stimulation of membrane-bound EGF receptors
      and EGF receptor-specific tyrosine kinase rather than by direct ligand activation
      of the ERalpha. Of biological significance, delayed onset of puberty and the
      absence of synchronization between reproductive behavior and ovulation was
      detected in intact mutant Wa-2 mice that express a naturally occurring point
      mutation in the EGF receptor. To our surprise, EGF-mediated behavior was
      independent of progesterone (P) and progesterone receptor (PR) since
      antiprogestins, PR antisense oligonucleotides, and targeted disruption of PR in
      ovariectomized transgenic mice failed to impede the display of lordosis after
      EGF. Finally, we also found that another growth factor, insulin-like growth
      factor-1, which provokes ER-dependent transcription in vitro, activates mating
      behavior in a similar E-independent manner. Thus, growth factor mediation of ER
      targeted function may be a universal feature in the rodent central nervous
      system, raising critical questions about the role of growth factors in mediating
      ER-dependent processes in development and reproduction.

PMID- 10894156
TI  - Regulable expression of inhibin A in wild-type and inhibin alpha null mice.
AB  - Exogenous regulation of protein expression creates the potential to examine the
      consequences of homeostatic Dysregulation in many physiological systems and, when
      used in transgenic mice, provides the capability of restoring a gene product to
      its knockout background without antigenicity issues. In this study, we used a
      mifeprisone-inducible system (the GeneSwitch system) to regulate the expression
      of inhibin A from the liver of mice. Inhibin is a heterodimeric protein
      (alpha/beta) wherein one of its subunits (beta) is capable of homodimerizing to
      form its physiological antagonist, activin (beta/beta). Inhibin is also expressed
      in two forms, A and B, as determined by the subtype of beta-subunit that
      dimerizes with the alpha-subunit (alpha/betaA or alpha/betaB). To utilize the
      GeneSwitch system, transgenic transactivator mice with liver-specific expression
      of a mifepristone-activated chimeric nuclear receptor (GLVP) were crossed with
      transgenic target mice containing a GVLP-responsive promoter upstream of polio
      virus IRES (internal ribosome entry site)-linked sequences coding for the alpha-
      and beta-subunits of inhibin A. This intercross produced "bigenic" mice capable
      of regulable expression of inhibin A from the liver. Overexpression of inhibin A
      in wild-type mice produced a phenotype wherein males had decreased testis size
      and females had a block in folliculogenesis at the early antral stage, findings
      similar to activin type IIA receptor (ActRIIA) null mice. These phenotypes were
      most likely due to suppressed serum FSH, confirming that the liver-derived
      inhibin A was secreted into the serum to down-regulate pituitary FSH levels.
      Furthermore, the generation of bigenic mice in the inhibin alpha null background
      allowed for the induction of inhibin A in inhibin alpha null male mice with
      subsequent rescue of these mice from their gonadal tumor-induced lethal
      phenotype. This work demonstrates the in vivo production of a heterodimeric
      hormone from a single inducible promoter to study its therapeutic and
      physiological effects. In addition, these studies are the first example of an
      inducible system being used to prevent a lethal knockout phenotype in an animal
      model.

PMID- 10894158
TI  - Residues within transmembrane helices 2 and 5 of the human gonadotropin-releasing
      hormone receptor contribute to agonist and antagonist binding.
AB  - To understand the ligand binding properties of the human GnRH receptor (hGnRH-R),
      24 site-specific mutants within transmembrane helices (TMH) 1, 2, and 5 and the
      extracellular loop 2 (E2) were generated. These mutants were analyzed by using a
      functional reporter gene assay, monitoring receptor signaling via adenylate
      cyclase to a cAMP-responsive element fused to Photinus pyralis luciferase. The
      functional behavior of 14 receptor mutants, capable of G-protein coupling and
      signaling, was studied in detail with different well described agonistic and
      antagonistic peptide ligands. Furthermore, the binding constants were determined
      in displacement binding experiments with the antagonist [125I]Cetrorelix. The
      substitution of residues K36, Q204, W205, H207, Q208, F20, F213, F216, and S217
      for alanine had no or only a marginal effect on ligand binding and signaling. In
      contrast, substitution of N87, Eg9, D9, R179, W206, Y211, F214, and T215 for
      alanine resulted in receptor proteins neither capable of ligand binding nor
      signal transduction. Within those mutants affecting ligand binding and signaling
      to various degrees, W101A, N102A, and N212Q differentiate between agonists and
      antagonists. Thus, in addition to N102 already described, the residues W101 in
      TMH2 and N212 in TMH5 are important for the architecture of the ligand-binding
      pocket. Based on the experimental data, three-dimensional models for binding of
      the superagonist D-Trp6-GnRH (Triptorelin) and the antagonist Cetrorelix to the
      hGnRH-R are proposed. Both decapeptidic ligands are bound to the receptor in a
      bent conformation with distinct interactions within the binding pocket formed by
      all TMHs, E2, and E3. The antagonist Cetrorelix with bulky hydrophobic N-terminal
      amino acids interacts with quite different receptor residues, a hint at the
      failure to induce an active, G protein-coupling receptor conformation.

PMID- 10894159
TI  - ITAM multiplicity and thymocyte selection: how low can you go?

PMID- 10894160
TI  - FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are
      essential for apoptosis mediated by TRAIL receptor 2.
AB  - Apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing
      ligand (TRAIL/APO-2L) has been shown to exert important functions during various
      immunological processes. The involvement of the death adaptor proteins
      FADD/MORT1, TRADD, and RIP and the apoptosis-initiating caspases-8 and -10 in
      death signaling by the two death-inducing TRAIL receptors 1 and 2 (TRAIL-R1 and
      TRAIL-R2) are controversial. Analysis of the native TRAIL death-inducing
      signaling complex (DISC) revealed ligand-dependent recruitment of FADD/MORT1 and
      caspase-8. Differential precipitation of ligand-stimulated TRAIL receptors
      demonstrated that FADD/MORT1 and caspase-8 were recruited to TRAIL-R1 and TRAIL
      R2 independently of each other. FADD/MORT1- and caspase-8-deficient Jurkat cells
      expressing only TRAIL-R2 were resistant to TRAIL-induced apoptosis. Thus,
      FADD/MORT1 and caspase-8 are essential for apoptosis induction via TRAIL-R2.

PMID- 10894161
TI  - Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death
      receptors 4 and 5.
AB  - Fas (APO-1/CD95) and tumor necrosis factor receptor 1 (TNFR1) trigger apoptosis
      by recruiting the apoptosis initiator caspase-8 through the adaptor FADD. Fas
      binds FADD directly, whereas TNFR1 binds FADD indirectly, through TRADD. TRADD
      alternatively recruits the NF-kappaB-inducing adaptor RIP. The TNF homolog
      Apo2L/TRAIL triggers apoptosis through two distinct death receptors, DR4 and DR5;
      however, receptor over-expression studies have yielded conflicting results on the
      ligand's signaling mechanism. Apo2L/TRAIL induced homomeric and heteromeric
      complexes of DR4 and DR5 and stimulated recruitment of FADD and caspase-8 and
      caspase-8 activation in nontransfected cells. TRADD and RIP, which bound TNFR1,
      did not bind DR4 and DR5. Thus, Apo2L/TRAIL and FasL initiate apoptosis through
      similar mechanisms, and FADD may be a universal adaptor for death receptors.

PMID- 10894162
TI  - DFF45/ICAD can be directly processed by granzyme B during the induction of
      apoptosis.
AB  - Granzyme B (GzmB) is a component of cytotoxic lymphocyte granules that can
      rapidly initiate apoptosis in target cells. While several procaspases are cleaved
      and activated by GzmB, the absolute requirement of caspase activation for GzmB
      induced apoptosis is controversial. In this report, we demonstrate that GzmB can
      initiate apoptosis in the absence of caspase-3 activity by directly cleaving
      DFF45/ICAD to liberate activated DFF40/CAD. DFF45/ICAD cleavage occurs less
      efficiently in cells that lack caspase-3 activity, suggesting that the caspases
      normally amplify the GzmB death signal. DFF45/ICAD-deficient mouse embryo
      fibroblasts are partially resistant to GzmB-induced death, demonstrating the
      biological importance of DFF45/ICAD for GzmB-mediated apoptosis.

PMID- 10894163
TI  - Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis
      and embryonic development.
AB  - Casper (c-FLIP) associates with FADD and caspase-8 in signaling complexes
      downstream of death receptors like Fas. We generated Casper-deficient mice and
      cells and noted a duality in the physiological functions of this molecule. casper
      /- embryos do not survive past day 10.5 of embryogenesis and exhibit impaired
      heart development. This phenotype is reminiscent of that reported for FADD-/- and
      caspase-8-/- embryos. However, unlike FADD-/- and caspase-8-/- cells, casper-/-
      embryonic fibroblasts are highly sensitive to FasL- or TNF-induced apoptosis and
      show rapid induction of caspase activities. NF-kappaB and JNK/SAPK activation is
      intact in TNF-stimulated casper-/- cells. These results suggest that Casper has
      two distinct roles: to cooperate with FADD and caspase-8 during embryonic
      development and to mediate cytoprotection against death factor-induced apoptosis.

PMID- 10894164
TI  - Cell-type-restricted binding of the transcription factor NFAT to a distal IL-4
      enhancer in vivo.
AB  - By DNase I hypersensitivity analysis, we have identified an inducible,
      cyclosporin A-sensitive enhancer located 3' of the interleukin-4 (IL-4) gene. The
      enhancer binds the Th2-specific transcription factor GATA3 in vivo but is not
      perceptibly influenced by the absence of a second Th2-specific factor, cMaf. The
      antigen-inducible transcription factor NFAT1 binds the IL-4 enhancer and the IL-4
      promoter only in stimulated Th2 cells; conversely, NFAT1 binds to the interferon
      (IFN)-gamma promoter only in stimulated Th1 cells. Our results support a model
      whereby transcription factors such as NFAT1, which are nonselectively induced in
      antigen-stimulated T cells, gain access to cytokine regulatory regions only in
      the appropriate subset of differentiated T cells in vivo. This restricted access
      enables antigen-dependent and subset-specific transcription of cytokine genes.

PMID- 10894165
TI  - Fetal and adult hematopoietic stem cells require beta1 integrin function for
      colonizing fetal liver, spleen, and bone marrow.
AB  - Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a
      prerequisite for the establishment of hematopoiesis during embryogenesis and
      after bone marrow transplantation. We show that beta1 integrin-deficient HSCs
      from the para-aortic splanchnopleura and the fetal blood had hematolymphoid
      differentiation potential in vitro and in fetal organ cultures but were unable to
      seed fetal and adult hematopoietic tissues. Adult beta1 integrin null HSCs
      isolated from mice carrying loxP-tagged beta1 integrin alleles and ablated for
      beta1 integrin expression by retroviral cre transduction failed to engraft
      irradiated recipient mice. Moreover, absence of beta1 integrin resulted in
      sequestration of HSCs in the circulation and their reduced adhesion to
      endothelioma cells. These findings define beta1 integrin as an essential adhesion
      receptor for the homing of HSCs.

PMID- 10894166
TI  - Specialized contributions by alpha(1,3)-fucosyltransferase-IV and FucT-VII during
      leukocyte rolling in dermal microvessels.
AB  - Noninflamed skin venules support constitutive leukocyte rolling. P-selectin
      controls the rolling frequency, whereas E-selectin dictates rolling velocity
      (Vroll). Fucosylated selectin ligands are essential for all interactions, as
      rolling was absent in mice doubly deficient in alpha1,3-fucosyltransferase (FucT)
      IV and FucT-VII. The rolling fraction was reduced in FucT-VII-/- animals but
      normal in FucT-IV-/- mice. However, Vroll was markedly increased in both strains.
      P-selectin ligands generated by FucT-VII are crucial for initial leukocyte
      tethering, whereas E-selectin ligands that permit maximum slowing of Vroll
      require simultaneous expression of FucT-IV and FucT-VII. These results
      demonstrate a role for FucT-IV in selectin-dependent adhesion and suggest that
      the endothelial selectins and FucTs have distinct but overlapping functions in
      the immunosurveillance of the skin.

PMID- 10894167
TI  - CD4+ T cell--mediated tumor rejection involves inhibition of angiogenesis that is
      dependent on IFN gamma receptor expression by nonhematopoietic cells.
AB  - Immunity against MHC class II tumors can be mediated by CD4+ T cells in the
      effector phase through an unknown mechanism. We show that this is IFN gamma
      dependent but does not require IFN gamma receptor (IFN gamma R) expression on
      tumor cells, T cells, or other hematopoietic cells and that IFN gamma R
      expression is not necessary in the priming phase. However, tumor immunity
      requires IFN gamma R expression on nonhematopoietic cells in the effector phase
      and involves inhibition of tumor-induced angiogenesis. This shows that an
      effective anti-tumor response involves communication between CD4+ T cells and
      nonhematopoietic cells, most likely within the tumor stroma, and that tumor
      immunity must not entirely rely on direct tumor cell killing.

PMID- 10894168
TI  - Rapid evolution of NK cell receptor systems demonstrated by comparison of
      chimpanzees and humans.
AB  - That NK cell receptors engage fast-evolving MHC class I ligands suggests that
      they, too, evolve rapidly. To test this hypothesis, the structure and class I
      specificity of chimpanzee KIR and CD94:NKG2 receptors were determined and
      compared to their human counterparts. The KIR families are divergent, with only
      three KIR conserved between chimpanzees and humans. By contrast, CD94:NKG2
      receptors are conserved. Whereas receptors for polymorphic class I are divergent,
      those for nonpolymorphic class I are conserved. Although chimpanzee and human NK
      cells exhibit identical receptor specificities for MHC-C, they are mediated by
      nonorthologous KIR. These results demonstrate the rapid evolution of NK cell
      receptor systems and imply that "catching up" with class I is not the only force
      driving this evolution.

PMID- 10894169
TI  - Structural basis of peptide binding and presentation by the type I diabetes
      associated MHC class II molecule of NOD mice.
AB  - We have determined the crystal structure of I-Ag7, an integral component in
      murine type I diabetes development. Several features distinguish I-Ag7 from other
      non-autoimmune-associated MHC class II molecules, including novel peptide and
      heterodimer pairing interactions. The binding groove of I-Ag7 is unusual at both
      terminal ends, with a potentially solvent-exposed channel at the base of the P1
      pocket and a widened entrance to the P9 pocket. Peptide binding studies with
      variants of the hen egg lysozyme I-Ag7 epitope HEL(11-25) support a comprehensive
      structure-based I-Ag7 binding motif. Residues critical for T cell recognition
      were investigated with a panel of HEL(11-25)-restricted clones, which uncovered
      P1 anchor-dependent structural variations. These results establish a framework
      for future experiments directed at understanding the role of I-Ag7 in
      autoimmunity.

PMID- 10894170
TI  - Dendritic cells permit identification of genes encoding MHC class II-restricted
      epitopes of transplantation antigens.
AB  - Minor or histocompatibility (H) antigens are recognized by CD4+ and CD8+ T
      lymphocytes as short polymorphic peptides associated with MHC molecules. They are
      the targets of graft versus host and graft versus leukemia responses following
      bone marrow transplantation between HLA-identical siblings. Several genes
      encoding class I-restricted minor H epitopes have been identified, but approaches
      used for these have proved difficult to adapt for cloning class II-restricted
      minor H genes. We have combined the unique antigen-presenting properties of
      dendritic cells and high levels of episomal expression following transfection of
      COS cells to identify a Y chromosome gene encoding two HY peptide epitopes, HYAb
      and HYEk.

PMID- 10894171
TI  - Retinoic acid early inducible genes define a ligand family for the activating
      NKG2D receptor in mice.
AB  - Here we describe a family of GPI-anchored cell surface proteins that function as
      ligands for the mouse activating NKG2D receptor. These molecules are encoded by
      the retinoic acid early inducible (RAE-1) and H60 minor histocompatibility
      antigen genes on mouse chromosome 10 and show weak homology with MHC class I.
      Expression of the NKG2D ligands is low or absent on normal, adult tissues;
      however, they are constitutively expressed on some tumors and upregulated by
      retinoic acid. Ectopic expression of RAE-1 and H60 confers target susceptibility
      to NK cell attack. These studies identify a family of ligands for the activating
      NKG2D receptor on NK and T cells, which may play an important role in innate and
      adaptive immunity.

PMID- 10894172
TI  - Dexmedetomidine-induced stimulation of glutamine oxidation in astrocytes: a
      possible mechanism for its neuroprotective activity.
AB  - Dexmedetomidine is a highly specific alpha2-adrenergic agonist, which is used
      clinically as an anesthetic adjuvant and in animal experiments has a
      neuroprotective effect during ischemia. The current study showed that
      dexmedetomidine enhances glutamine disposal by oxidative metabolism in
      astrocytes. This effect occurs at pharmacologically relevant concentrations. It
      is exerted on alpha2-adrenergic receptors and not on imidazoline-preferring
      sites, and it is large enough to reduce the availability of glutamine as a
      precursor of neurotoxic glutamate.

PMID- 10894173
TI  - Kinetic analysis of the 5-HT2A ligand [11C]MDL 100,907.
AB  - The goal of this study was to develop a suitable kinetic analysis method for
      quantification of 5-HT2A receptor parameters with [11C]MDL 100,907. Twelve
      control studies and four preblocking studies (400 nmol/kg unlabeled MDL 100,907)
      were performed in isoflurane-anesthetized rhesus monkeys. The plasma input
      function was determined from arterial blood samples with metabolite measurements
      by extraction in ethyl acetate. The preblocking studies showed that a two-tissue
      compartment model was necessary to fit the time activity curves of all brain
      regions including the cerebellum--in other words, the need for two compartments
      is not proof of specific binding. Therefore, a three-tissue compartment model was
      used to analyze the control studies, with three parameters fixed based on the
      preblocking data. Reliable fits of control data could be obtained only if no more
      than three parameters were allowed to vary. For routine use of [11C]MDL 100,907,
      several simplified methods were evaluated. A two-tissue (2T') compartment with
      one fixed parameter was the most reliable compartmental approach; a one
      compartment model failed to fit the data adequately. The Logan graphical approach
      was also tested and produced comparable results to the 2T' model. However, a
      simulation study showed that Logan analysis produced a larger bias at higher
      noise levels. Thus, the 2T' model is the best choice for analysis of [11C]MDL
      100,907 studies.

PMID- 10894174
TI  - Cerebral hemodynamics in human acute ischemic stroke: a study with diffusion- and
      perfusion-weighted magnetic resonance imaging and SPECT.
AB  - Nineteen patients with acute ischemic stroke (<24 hours) underwent diffusion
      weighted and perfusion-weighted (PWI) magnetic resonance imaging at the acute
      stage and 1 week later. Eleven patients also underwent technetium-99m ethyl
      cysteinate dimer single-photon emission computed tomography (SPECT) at the acute
      stage. Relative (ischemic vs. contralateral control) cerebral blood flow
      (relCBF), relative cerebral blood volume, and relative mean transit time were
      measured in the ischemic core, in the area of infarct growth, and in the
      eventually viable ischemic tissue on PWI maps. The relCBF was also measured from
      SPECT. There was a curvilinear relationship between the relCBF measured from PWI
      and SPECT (r = 0.854; P < 0.001). The tissue proceeding to infarction during the
      follow-up had significantly lower initial CBF and cerebral blood volume values on
      PWI maps (P < 0.001) than the eventually viable ischemic tissue had. The best
      value for discriminating the area of infarct growth from the eventually viable
      ischemic tissue was 48% for PWI relCBF and 87% for PWI relative cerebral blood
      volume. Combined diffusion and perfusion-weighted imaging enables one to detect
      hemodynamically different subregions inside the initial perfusion abnormality.
      Tissue survival may be different in these subregions and may be predicted.

PMID- 10894175
TI  - Coupling of neural activation to blood flow in the somatosensory cortex of rats
      is time-intensity separable, but not linear.
AB  - Changes in cerebral blood flow (CBF) because of functional activation are used as
      a surrogate for neural activity in many functional neuroimaging studies. In these
      studies, it is often assumed that the CBF response is a linear-time invariant
      (LTI) transform of the underlying neural activity. By using a previously
      developed animal model system of electrical forepaw stimulation in rats (n = 11),
      laser Doppler measurements of CBF, and somatosensory evoked potentials,
      measurements of neural activity were obtained when the stimulus duration and
      intensity were separately varied. These two sets of time series data were used to
      assess the LTI assumption. The CBF data were modeled as a transform of neural
      activity (N1-P2 amplitude of the somatosensory evoked potential) by using first
      order (linear) and second-order (nonlinear) components. Although a pure LTI model
      explained a large amount of the variance in the data for changes in stimulus
      duration, our results demonstrated that the second-order kernel (i.e., a
      nonlinear component) contributed an explanatory component that is both
      statistically significant and appreciable in magnitude. For variations in
      stimulus intensity, a pure LTI model explained almost all of the variance in the
      CBF data. In particular, the shape of the CBF response did not depend on
      intensity of neural activity when duration was held constant (time-intensity
      separability). These results have important implications for the analysis and
      interpretation of neuroimaging data.

PMID- 10894176
TI  - Investigation of estrogen status and increased stroke sensitivity on cerebral
      blood flow after a focal ischemic insult.
AB  - Recently the authors have shown that female stroke-prone spontaneously
      hypertensive rats (SHRSPs) in proestrus (high endogenous estrogen), sustain more
      than 20% smaller infarcts after middle cerebral artery occlusion (MCAO) compared
      with SHRSPs in metestrus (low endogenous estrogen). Because estrogen has
      vasodilator properties, the authors investigated whether the estrous state
      influences cerebral blood flow (CBF) after MCAO. CBF was measured 2.5 hours after
      a distal MCAO by [14C]iodo-antipyrine autoradiography in conscious SHRSPs either
      in metestrus or in proestrus. There were no significant differences in CBF when
      analyzed either at predetermined anatomic regions or by cumulative distribution
      analysis of areas with flow <25 mL/100 g/min. As a positive internal control, the
      authors compared results in SHRSPs with those in their normotensive reference
      strain, Wistar Kyoto rat. SHRSPs displayed more severe and widespread ischemia
      than Wistar Kyoto rats. Thus, the absence of demonstrable CBF differences between
      estrous states appears to be unrelated to the CBF measurement paradigm. In
      conclusion, the smaller infarct size afforded in proestrus in SHRSPs is unlikely
      to be due to an influence on CBF.

PMID- 10894177
TI  - Evolution of brain infarction after transient focal cerebral ischemia in mice.
AB  - The evolution of brain infarction after transient focal cerebral ischemia was
      studied in mice using multiparametric imaging techniques. One-hour focal cerebral
      ischemia was induced by occluding the middle cerebral artery using the
      intraluminal filament technique. Cerebral protein synthesis (CPS) and the
      regional tissue content of adenosine triphosphate (ATP) were measured after
      recirculation times from 0 hours to 3 days. The observed changes were correlated
      with the expression of the mRNAs of hsp-70, c-fos, and junB, as well as the
      distribution of DNA double-strand breaks, visualized by TUNEL. At the end of 1
      hour of ischemia, protein synthesis was suppressed in a larger tissue volume than
      ATP in accordance with the biochemical differentiation between core and penumbra.
      Hsp70 mRNA was selectively expressed in the cortical penumbra, whereas c-fos and
      junB mRNAs were increased both in the lateral part of the penumbra and in the
      ipsilateral cingulate cortex with normal metabolism. During reperfusion after
      withdrawal of the intraluminal filament, suppression of CPS persisted except in
      the most peripheral parts of the middle cerebral artery territory, in which it
      recovered between 6 hours and 3 days. ATP, in contrast, returned to normal levels
      within 1 hour but secondarily deteriorated from 3 hours on until, between 1 and 3
      days, the ATP-depleted area merged with that of suppressed protein synthesis
      leading to delayed brain infarction. Hsp70 mRNA, but not c-fos and junB, was
      strongly expressed during reperfusion, peaking at 3 hours after reperfusion.
      TUNEL-positive cells were detected from 3 hours on, mainly in areas with
      secondary ATP depletion. These results stress the importance of an early recovery
      of CPS for the prevention of ischemic injury and suggest that TUNEL is an
      unspecific response of delayed brain infarction.

PMID- 10894178
TI  - Influence of blood viscosity on blood flow in the forebrain but not hindbrain
      after carotid occlusion in rats.
AB  - That cerebral blood flow remains unchanged at an increased blood viscosity, as
      long as the vascular supply is not compromised, was tested. To induce a reduced
      blood supply of some parts of the brain and to keep the supply unchanged in
      others both carotid arteries were occluded in anesthetized, ventilated rats. By
      this procedure, blood supply to the rostral brain, but not to the brainstem and
      cerebellum, was compromised. Blood viscosity was increased by intravenous
      infusion of 20% polyvinylpyrrolidone (high viscosity group) or decreased by
      infusion of 5% albumin (low viscosity group). Cerebral blood flow was measured by
      the [14C]iodoantipyrine method in 50 complete coronal sections of the rostral
      brain and 22 complete coronal sections of the brainstem and cerebellum in each
      rat. In the high viscosity group, mean cerebral blood flow of the rostral brain
      was significantly lower (46 +/- 7 mL/100 g(-1) x min(-1)) than in the low
      viscosity group (82 +/- 18 mL/100 g(-1) x min(-1)). No differences could be
      observed in brainstem and cerebellum between both groups (162 +/- 29 mL/100 g(-1)
      x min(-1) vs. 156 +/- 18 mL/100 g(-1) x min(-1)). Local analysis of cerebral
      blood flow in different brain structures of the coronal sections showed the same
      identical results; i.e., in 29 of the 31 brain structures analyzed in rostral
      brain, local cerebral blood flow was lower in the high viscosity group, whereas
      no differences could be observed in the 11 brain structures analyzed in the
      brainstem and cerebellum. It is concluded that under normal conditions cerebral
      blood flow can be maintained at an increased blood viscosity by a compensatory
      vasodilation. When the capacity for vasodilation is exhausted by occlusion of
      supplying arteries, an increased blood viscosity results in a decrease of
      cerebral blood flow.

PMID- 10894179
TI  - Ischemia-induced interleukin-6 as a potential endogenous neuroprotective cytokine
      against NMDA receptor-mediated excitotoxicity in the brain.
AB  - In the brain, the expression of the pleiotropic cytokine interleukin-6 (IL-6) is
      enhanced in various chronic or acute central nervous system disorders. However,
      the significance of IL-6 production in such neuropathologic states remains
      controversial. The present study investigated the role of IL-6 after cerebral
      ischemia. First, the authors showed that focal cerebral ischemia in rats early up
      regulated the expression of IL-6 mRNA, without affecting the transcription of its
      receptors (IL-6Ralpha and gp130). Similarly, the striatal injection of N-methyl-D
      aspartate (NMDA) in rats, a paradigm of excitotoxic injury, activated the
      expression of IL-6 mRNA. The involvement of glutamatergic receptor activation was
      further investigated by incubating cortical neurons with NMDA or alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionate (AMPA). NMDA and ionomycin (a calcium
      ionophore) up-regulated IL-6 mRNA, suggesting that neurons may produce IL-6 in
      response to the calcium influx mediated through NMDA receptors. The potential
      role of IL-6 during ischemic/excitotoxic insults was then studied by testing the
      effect of IL-6 against apoptotic or excitotoxic challenges in cortical cultures.
      IL-6 did not prevent serum deprivation- or staurosporine-induced apoptotic
      neuronal death, or AMPA/kainate-mediated excitotoxicity. However, in both mixed
      and pure neuronal cultures, IL-6 dose-dependently protected neurons against NMDA
      toxicity. This effect was blocked by a competitive inhibitor of IL-6. Overall,
      the results suggest that the up-regulation of IL-6 induced by cerebral ischemia
      could represent an endogenous neuroprotective mechanism against NMDA receptor
      mediated injury.

PMID- 10894180
TI  - Inflammatory activation of human brain endothelial cells by hypoxic astrocytes in
      vitro is mediated by IL-1beta.
AB  - Leukocyte infiltration into the brain contributes to the development of ischemic
      brain damage and is mediated by endothelial/leukocyte adhesion molecules,
      cytokines, and chemokines released by ischemic brain cells. In this study, we
      provide evidence that human astrocytes (FHAs) subjected to in vitro hypoxia
      produce proinflammatory mediator(s) capable of up-regulating inflammatory genes,
      including intercellular adhesion molecule-1, interleukin (IL)-1beta, tumor
      necrosis factor-alpha, IL-8, and monocyte chemotactic protein-1 (MCP-1) in human
      cerebromicrovascular endothelial cells (HCECs). FHAS were exposed to hypoxia in
      an anaerobic chamber for 4 hours, followed by reoxygenation for 24 hours.
      Astrocyte-conditioned media (ACM) collected from normoxic FHAS or FHAS subjected
      to hypoxia/reoxygenation were applied to HCEC cultures for 4 to 24 hours.
      Semiquantitative reverse transcription-polymerase chain reaction,
      immunocytochemistry, and enzyme-linked immunosorbent assay demonstrated up
      regulation of intercellular adhesion molecule-1 in HCECs exposed to hypoxic ACM.
      A pronounced elevation in cytokine IL-1beta and tumor necrosis factor-alpha, and
      chemokine IL-8 and MCP-1 mRNA, accompanied by increased release of immunoreactive
      cytokines and chemokines into cell media was observed in HCECs exposed to hypoxic
      ACM. Hypoxia/reoxygenation induced a transient (4 to 18 hours of reoxygenation)
      up-regulation of IL-1beta mRNA in FHAS and a two- to threefold increase in IL
      1beta levels secreted into ACM. Pretreatment of FHAS with 10 micromol/L
      dexamethasone inhibited both hypoxia-induced expression/secretion of IL-1beta and
      the ability of hypoxic ACM to induce inflammatory phenotype in HCECs. The ability
      of hypoxic ACM to up-regulate inflammatory genes in HCECs was inhibited in the
      presence of IL-1 receptor antagonist (IL-1Ra) and by pretreating ACM with the
      blocking anti-IL-1beta antibody. These findings strongly implicate IL-1beta
      secreted by hypoxic astrocytes in triggering inflammatory activation of HCECs and
      thereby influencing inflammatory responses at the site of the blood-brain
      barrier.

PMID- 10894181
TI  - Leukocyte-endothelium interactions in pial venules during the early and late
      reperfusion period after global cerebral ischemia in gerbils.
AB  - The contribution of leukocytes to secondary brain damage after cerebral ischemia
      is still under discussion. The purpose of the present study was to examine the
      pial microcirculation after global cerebral ischemia while focusing on leukocyte
      endothelium interactions during the early and late reperfusion period of up to 4
      days. A closed cranial window technique that leaves the dura mater intact was
      used. Global cerebral ischemia of 15 minutes' duration was induced in male
      Mongolian gerbils (n = 91). Pial microcirculation was observed by intravital
      fluorescence microscopy. Leukocyte-endothelium interactions (LEIs) in pial
      venules, vessel diameters, capillary density, and regional microvascular blood
      flow measured by laser Doppler flowmetry were quantified during 3 hours of
      reperfusion and in intervals up to 4 days after ischemia. Within 3 hours of
      reperfusion, the number of leukocytes (cells/100 microm x minute) rolling along
      or adhering to the venular endothelium increased from 0.1 +/- 0.2 to 28.4 +/-
      17.4 (P < 0.01 vs. control) and from 0.2 +/- 0.2 to 4.0 +/- 3.8 (P < 0.05),
      respectively. There was no capillary plugging by leukocytes; capillary density
      remained unchanged. In the late reperfusion period, at 7 hours after ischemia,
      LEIs had returned to baseline values. Furthermore, from 12 hours to 4 days after
      ischemia, no LEIs were observed. Changes in regional microvascular blood flow did
      not correlate with LEIs. Global cerebral ischemia of 15 minutes' duration induces
      transient LEIs that reach a maximum within 3 hours of reperfusion and return to
      baseline at 7 hours after ischemia. LEIs are not related to changes in
      microvascular perfusion, which suggests mainly that the expression of adhesion
      receptors is necessary to induce LEIs rather than rheologic factors. It seems
      unlikely that this short-lasting activation of leukocytes can play a role in the
      development of secondary brain damage.

PMID- 10894182
TI  - ME3277, a GPIIb/IIIa antagonist reduces cerebral infarction without enhancing
      intracranial hemorrhage in photothrombotic occlusion of rabbit middle cerebral
      artery.
AB  - GPIIb/IIIa antagonists are expected to have a beneficial effect on acute cerebral
      infarction, however, the occurrence of intracranial hemorrhage has not been as
      widely investigated. A rabbit focal thrombotic occlusion model of the middle
      cerebral artery was established by creating a photochemical reaction between
      green light and Rose Bengal. Hemorrhagic transformation was common in the area of
      cerebral infarction. Using this model, the effect of a GPIIb/IIIa antagonist,
      ME3277 (low dose, (L); 0.15 mg/kg + 0.125 mg/kg x h, middle dose, (M); 0.3 mg/kg
      + 0.25 mg/kg x h and high dose, (H); 0.6 mg/kg + 0.5 mg/kg x h), aspirin (20
      mg/kg) and sodium ozagrel (thromboxane A2 synthase inhibitor, 1 mg/kg + 2 mg/ kg
      x h) were evaluated. Drugs were intravenously administrated 30 minutes after the
      photochemical reaction for 24 hours. Aspirin inhibited the ex vivo platelet
      aggregation induced by arachidonic acid and collagen but not by adenosine
      diphosphate (ADP), while sodium ozagrel only inhibited the arachidonic acid
      induced aggregation. ME3277 dose-dependently inhibited the platelet aggregation
      induced by all the inducers (approximately 60% in L, 80% in M, and 90% in H). At
      24 hours of middle cerebral artery (MCA) occlusion, infarct volume was
      significantly reduced by aspirin and each dose of ME3277. These agents improved
      neurologic deficits, with ME3277 being more potent than aspirin. Sodium ozagrel
      did not alter the infarct volume nor neurologic deficits. No drug was found to
      worsen hemorrhage volume despite increasing bleeding time (2-3 fold) in the skin.
      In this model, the occluded artery was spontaneously recanalized and re
      thrombosed frequently. One mechanism by which antiplatelet agents reduced infarct
      volume was inhibition of rethrombosis of the MCA. These results suggest that
      treatment with a GPIIb/IIIa antagonist is a useful intervention for acute
      cerebral infarction prolonging dose bleeding time to 3 times the basal value.

PMID- 10894183
TI  - Brain injury and cerebrovascular fibrin deposition correlate with reduced
      antithrombotic brain capillary functions in a hypertensive stroke model.
AB  - Hemostasis factors may influence the pathophysiology of stroke. The role of brain
      hemostasis in ischemic hypertensive brain injury is not known. We studied
      ischemic injury in spontaneously hypertensive rats in relation to cerebrovascular
      fibrin deposition and activity of different hemostasis factors in brain
      microcirculation. In spontaneously hypertensive rats subjected to transient
      middle cerebral artery occlusion versus normotensive Wistar-Kyoto (W-K) rats,
      infarct and edema volumes were increased by 6.1-fold (P < 0.001) and 5.8-fold (P
      < 0.001), respectively, the cerebral blood flow (CBF) reduced during middle
      cerebral artery occlusion (MCAO) by 55% (P < 0.01), motor neurologic score
      increased by 6.9-fold (P < 0.01), and cerebrovascular fibrin deposition increased
      by 6.8-fold (P < 0.01). Under basal conditions, brain capillary protein C
      activation and tissue plasminogen activator activity were reduced in
      spontaneously hypertensive rats compared with Wistar-Kyoto rats by 11.8-fold (P <
      0.001) and 5.1-fold (P < 0.001), respectively, and the plasminogen activator
      inhibitor-1 antigen and tissue factor activity were increased by 154-fold (P <
      0.00001) and 74% (P < 0.01), respectively. We suggest that hypertension reduces
      antithrombotic mechanisms in brain microcirculation, which may enhance
      cerebrovascular fibrin deposition and microvascular obstructions during transient
      focal cerebral ischemia, which results in greater neuronal injury.

PMID- 10894184
TI  - The role of human papillomavirus in gynecological diseases.
AB  - Papanicolaou (Pap) smears of the cervix and biopsies of the cervix, vagina,
      vulva, and penis are a substantial portion of the work load of any anatomic
      pathology laboratory. The importance of samples from these sites is highlighted
      by the fact that their most common disease is dysplasia, which is sexually
      transmitted and a recognized risk factor for carcinoma. Human papillomavirus
      (HPV) is an essential co-factor for the development of lower genital tract
      dysplasia. Molecular testing for HPV has revealed a great deal about the
      pathophysiology of dysplasia and its evolution to carcinoma. Importantly, it now
      allows diagnostic pathologists the opportunity to be more accurate in their
      assessment of common conditions such as Pap smears of squamous atypia and
      biopsies equivocal for dysplasia. This review highlights the role of HPV in the
      evolution of disease in the lower genital tract and stresses the utility of HPV
      testing to the diagnostic pathologist.

PMID- 10894185
TI  - Genetic disorders of calcium and phosphorus metabolism.
AB  - The genetic control of calcium, phosphorus, cartilage, and bone metabolism is
      discussed, and many of the genes involved in this process are described.
      Mutations in these genes that lead to the clinical disorders associated with
      hypercalcemia, hypocalcemia, rickets, and osteochondrodystrophies are delineated.

PMID- 10894186
TI  - The health effects of moderate alcohol intake in humans: an epidemiologic review.
AB  - A large body of scientific evidence associates the moderate intake of alcohol
      with reduced mortality among middle-aged and older people in industrialized
      societies. This association is due largely to a reduced risk of death from
      coronary heart disease, which appears to outweigh any possible adverse effects of
      moderate drinking. The regular consumption of small amounts of alcohol is more
      healthful than the sporadic consumption of larger amounts. No beneficial effect
      of moderate drinking on mortality has been demonstrated in young adults
      (premenopausal women and men who have not reached their forties). It is
      theoretically possible that moderate drinking in young adulthood might reduce the
      risk of later heart disease; however, this has not been clearly demonstrated. For
      some individuals (e.g., those who cannot keep their drinking moderate, pregnant
      women, and those who are taking medications that may interact adversely with
      alcoholic beverages), the risks of alcohol consumption, even in moderation,
      outweigh any potential benefits. Because even small amounts of alcohol can impair
      judgment and coordination, no one should drink alcoholic beverages, even in
      moderation, before driving a motor vehicle or performing other activities that
      involve attention and skill.

PMID- 10894187
TI  - External quality mechanisms for health care: summary of the ExPeRT project on
      visitatie, accreditation, EFQM and ISO assessment in European Union countries.
      External Peer Review Techniques. European Foundation for Quality Management.
      International Organization for Standardization.
AB  - This paper is a summary of the operation, findings and conclusions of a European
      Union project on external peer review techniques, termed 'ExPeRT', to research
      the scope, mechanisms and use of external quality mechanisms in the improvement
      of health care. Many of the themes outlined are described in detail in other
      papers that have been prepared specifically for this issue of The International
      Journal for Quality in Health Care. Although the emphasis of this project and of
      this issue of the Journal is on Europe, the conclusions are more widely relevant.

PMID- 10894188
TI  - External peer review in Europe: an overview from the ExPeRT Project. External
      Peer Review Techniques.
AB  - OBJECTIVE: This paper aims to evaluate the use and development of external peer
      review models and to identify where the main models are used in European Union
      member states and countries with reciprocal research agreements with the European
      Union. DESIGN: The ExPeRT (external peer review techniques) project research team
      conducted a series of fact-finding missions to all participating European
      nations. Study participants. I. Blomberg, Sweden; L. Bohigas, Spain; S. Cucic,
      The Netherlands; P. Morosini, Italy. The Project is led by C. Shaw, UK and is
      managed by C. Heaton, CASPE Research. RESULTS: We identified four main external
      peer review models aimed at measuring the quality of service management and
      delivery: health care accreditation, the International Organization for
      Standardization ISO 9000 standards, the European Foundation for Quality
      Management Excellence Model and visitatie, which is Dutch for 'visitation' or
      peer review-based schemes. DISCUSSION: ExPeRT has demonstrated that in principle,
      convergence of the four main models in order to gain from each model's key
      strengths is feasible. Whether convergence is practical, depends upon the
      willingness of governments, health service providers, health care quality
      professionals and organizations to come together and adopt the recommendations of
      the ExPeRT project.

PMID- 10894189
TI  - Re-engineering trust: the adoption and adaption of four models for external
      quality assurance of health care services in western European health care
      systems.
AB  - Accreditation, ISO, EFQLM and visitatie are, in essence, control mechanisms in
      health care systems. An analysis is provided of the way the four models have been
      adopted and adapted in European health care systems over the past decade. After a
      short discussion of the major reforms in the European health care systems in the
      direction of regulated markets, deregulation and decentralization, the features
      of the four models are highlighted and it is explained how each of them can help
      to fill the 'accountability gap' between health care providers on the one hand
      and patients, financiers and governments on the other. The quality system
      perspective of ISO, the quality management development perspective of EFQM, the
      health care organization perspective of accreditation and the professional
      perspective of visitatie can each be appropriate given the balance of power
      between parties in the health care system and the focus and scope of
      accountability. Although a general convergence between the four models can be
      observed, actual convergence will depend on their adoption in specific health
      system contexts. Potential pitfalls for further convergence are the differences
      in distribution of responsibilities for quality of care among the various
      European countries, the drift away from clinical decision making, bureaucratic
      tendencies and too much focus on efficiency and patient empowerment compared with
      attention to medical effectiveness.

PMID- 10894190
TI  - The EFQM excellence model: European and Dutch experiences with the EFQM approach
      in health care. European Foundation for Quality Management.
AB  - One way to meet the challenges in creating a high performance organization in
      health care is the approach of the European Foundation for Quality Management
      (EFQM). The Foundation is in the tradition of the American Malcolm Baldrige Award
      and was initiated by the European Commission and 14 European multi-national
      organizations in 1988. The essence of the approach is the EFQM Model, which can
      be used as a self-assessment instrument on all levels of a health care
      organization and as an auditing instrument for the Quality Award. In 1999 the
      EFQM Model was revised but its principles remained the same. In The Netherlands
      many health care organizations apply the EFQM Model. In addition to improvement
      projects, peer review of professional practices, accreditation and certification,
      the EFQM Approach is used mainly as a framework for quality management and as a
      conceptualization for organizational excellence. The Dutch National Institute for
      Quality, the Instituut Nederlandse Kwaliteit, delivers training and supports self
      assessment and runs the Dutch quality award programme. Two specific guidelines
      for health care organizations, 'Positioning and Improving' and 'Self-Assessment',
      have been developed and are used frequently. To illustrate the EFQM approach in
      The Netherlands, the improvement project of the Jellinek Centre is described. The
      Jellinek Centre conducted internal and external assessments and received in 1996,
      as the first health care organization, the Dutch Quality Prize.

PMID- 10894191
TI  - Interpretations and variations of ISO 9000 in acute health care. International
      Organization for Standardization.
AB  - OBJECTIVE: This paper aims to address two questions related to the implementation
      of the ISO 9000 Quality Management System standard in the acute health care
      sector: which countries have developed specific nationwide
      guidelines/interpretations? and what variances exist between the different
      interpretations of the ISO 9002 standard? DESIGN: The study was carried out via
      an assessment of the available guideline documents for the use of ISO 9000 in the
      acute health care sector. The interpretation of each document was examined for
      common elements and deviations from the commonly agreed terms. SETTING: Worldwide
      in the acute health care sector (excluding that of laboratories). STUDY
      PARTICIPANTS: Eighty-two international ISO members and/or quality health care
      organizations. RESULTS: The results showed variation in the interpretations of
      the ISO 9000 standard. In total, 16 of the clauses/subclauses note distinct
      variations, between one or more of the documents, which could alter the
      perception of the system. CONCLUSION: From examination of the six identified
      guideline documents, the claim that ISO 9000 introduces quality systems which are
      comparable from one country to another is unfounded in the acute health care
      sector.

PMID- 10894192
TI  - Clinical indicators in accreditation: an effective stimulus to improve patient
      care.
AB  - The Australian Council on Healthcare Standards (ACHS) established the Care
      Evaluation Program (CEP) of clinical performance measures in its accreditation
      program to increase the clinical component of that program and to increase
      medical practitioner involvement in formal quality activities in their health
      care organizations. From the introduction of a set of generic indicators in 1993
      the program expanded through all of the various medical disciplines and from
      January 2000 there will be 18 sets (well over 200 indicators) in the program.
      More than half of Australia's acute hospitals (covering the majority of patient
      separations) are monitoring the indicators and reporting clinical data twice
      yearly to the ACHS. In turn they receive a 6-monthly feedback of aggregate and
      peer comparative results. The ACHS policy had no specific requirement for a set
      number of indicators to be monitored and it was not mandatory to achieve any
      specific data threshold to be accredited. However, where an organization's
      results differed unfavorably from those of its peers some action was expected.
      Qualitative information is also sent to the CEP and this has enabled a
      determination of the effectiveness of the indicators. There is documented
      evidence of improved management and numerous examples of improved patient
      outcomes. The program remains unique in the scope of the medical disciplines
      covered and in the formal provider involvement with indicator development. Both
      the clinical component of accreditation and clinician involvement in quality
      activities have been increased in an educational process. However, not all of the
      indicators are of equal value and a reduction in the number of indicators to a
      'core' group of the most reliable and responsive ones is in process.

PMID- 10894193
TI  - European Union health policy and its implications for national convergence.
AB  - This paper explores the relevance for health care of European Union (EU)
      legislation, regulation and policies. Reports, communications and other materials
      of the European Commission and other relevant European bodies are screened for
      their implications for health care, primarily on the national health system
      level. The paper provides a brief overview of EU history and its main
      institutions, followed by an analysis of health (care)-related provisions in the
      EU's main legal documents--its treaties. The impact of the EU actions on health
      protection is considered with regard to both actions in the field of public
      health and health protection requirements in its policies. In the public health
      area, information systems that are now being developed are discussed, followed by
      an outline of health protection requirements in EU policies that can have an
      impact on health systems. These policies are then analysed using the political
      factions model. Finally an attempt is made to predict future developments,
      stressing the need for a far-reaching synchronization of national systems.

PMID- 10894194
TI  - Moving to global standards for accreditation processes: the ExPeRT Project in a
      larger context. External Peer Review Techniques.
AB  - The ExPeRT (External Peer Review Techniques) Project, a European Union effort to
      examine and compare methods of health care evaluation currently in use, includes
      an assessment of accreditation as one such method. This article contributes to
      that examination by describing recent work, through the International Society for
      Quality in Health Care (ISQua), to investigate and to enhance the international
      comparability of national health care accreditation programs, both existing and
      newly emerging.

PMID- 10894195
TI  - Methods for external evaluation of health care institutions.
AB  - OBJECTIVE: To compare the methods used by external evaluators of health care
      institutions in Europe. METHODS: A common framework for analysis was designed by
      the authors and shared among the members of the ExPeRT Project. Each member
      prepared a description of a model and the results were compared in two workshops.
      RESULTS: Programmes share similarities in the methods used, but they differ in
      the focus and purpose of the evaluation. Differences in focus included whether a
      part or the whole of the institution is analysed and whether the review is
      patient or system centred. Different purposes of the programmes are reflected in
      the emphasis and use of the methodological tools: for instance, the appeal system
      is used only in the programmes that provide a certificate to the institution
      audited.

PMID- 10894197
TI  - Joint Commission International accreditation: relationship to four models of
      evaluation.
AB  - OBJECTIVE: To describe the components of the new Joint Commission International
      (JCI) accreditation program for hospitals, and compare this program with the four
      quality evaluation models described under the ExPeRT project (visitatie, ISO,
      EFQM, organizational accreditation). RESULTS: All the models have in common with
      the JCI program the use of explicit criteria or standards, and the use of
      external reviewers. The JCI program is clearly an organizational accreditation
      approach with evaluation of all the 'systems' of a health care organization. The
      JCI model evaluates the ability of an organization to assess and monitor its
      professional staff through internal mechanisms, in contrast with the external
      peer assessment used by the visitatie model. The JCI program provides a
      comprehensive framework for quality management in an organization, expanding the
      boundaries of the quality leadership and management found in the EFQM model, and
      beyond the quality control of the ISO model. The JCI organizational accreditation
      program was designed to permit international comparisons, difficult under the
      other models due to country specific variation. CONCLUSION: We believe that the
      organizational accreditation model, such as the international accreditation
      program, provides a framework for the convergence and integration of the
      strengths of all the models into a common health care quality evaluation model.

PMID- 10894196
TI  - Developments in professional quality assurance towards quality improvement: some
      examples of peer review in the Netherlands and the United Kingdom.
AB  - This study will explore new developments in three clinical peer review programmes
      in the UK and the visitatie programme in The Netherlands and how these programmes
      can be linked, in the future, with other quality systems. The information about
      the English peer review programmes was gathered by conducting four structured
      interviews with the programme coordinators (see Acknowledgements). Information
      about the Dutch visitatie programme was gathered by the author working with
      different visitatie programmes at the Dutch National Institute for Quality
      Improvement. Comparing new developments in the models of the Institute for
      Standardization of Organizations and the European Foundation for Quality
      Management, common changes are identified which seem to reflect elements viewed
      internationally as necessary in quality improvement. This study will examine if
      and how these elements are or will be included in the clinical peer review
      programmes in the UK and in visitatie in The Netherlands.

PMID- 10894198
TI  - Status of a health care quality review programme in South Africa.
AB  - This paper provides an overview of an accreditation programme for health care
      facilities in South Africa. It traces the origin of COHSASA (The Council for
      Health Service Accreditation of Southern Africa) which began as a pilot programme
      in 1992, to its current status as the only accreditation body in the country.
      There are brief descriptions of its structure, how it is governed, and how
      standards were developed and organized. The authors sketch a background of the
      unique sociopolitical context and legal developments within which the programme
      operates in South Africa and how the programme is contributing towards the new
      government's intention to provide equitable and quality health care to all its
      citizens. There is an outline of the principles on which the COHSASA programme is
      based and the structure and process of the programme. The programme incorporates
      an integrated, multi-disciplinary, continuous quality improvement approach with
      special emphasis on capacity building of hospital staff when necessary. The paper
      refers to groundbreaking research in Kwa-Zulu Natal where the impact of
      accreditation is being measured in a randomized control trial. It points to the
      benefits of accreditation being perceived in both public and private sectors of
      health care in South Africa and outlines some of the results of the program's
      implementation.

PMID- 10894199
TI  - Can European external peer review techniques be introduced and adopted into
      Taiwan's hospital accreditation system?

PMID- 10894200
TI  - The evolution of external quality evaluation: observations from the Joint
      Commission on Accreditation of Healthcare Organizations.
AB  - The Joint Commission on Accreditation of Healthcare Organizations, the oldest
      health care accrediting body in the world, currently accredits almost 20000
      organizations in the USA. Although continuing to be professionally-sponsored,
      accreditation's rapid growth in recent years has been driven by the external
      users of accreditation--government, purchasers, and public--rather than by the
      original users, the professionals themselves. This experience in the USA suggests
      that over time successful external quality evaluation mechanisms throughout the
      world will involve representatives of the public, purchasers, and government in
      establishing standards and setting policies. Without this involvement, these
      stakeholders are unlikely to find the mechanisms credible in addressing their
      needs, and will seek alternatives--adding cost and duplication to the external
      quality evaluation system. Successful mechanisms are also likely to provide more
      detailed information about an organization's performance to the public,
      purchasers, and the government, while creating evaluation processes that provide
      for innovation and support improvement in efficiency, as well as quality, through
      incorporation of aspects of the Baldrige and European Foundation for Quality
      Management approaches to organizational excellence. Finally, successful
      evaluation mechanisms are likely to create a special focus on the safety of care,
      incorporating aspects of the International Organization for Standardization's ISO
      9000 approach to quality management. While the specific nature, priority, and
      timing of these changes will differ from country to country, they are likely to
      influence the evolution of external quality evaluation throughout the world.
      External evaluation of health care organizations' quality holds great promise,
      but its long-term success depends on responding to all those who will want to
      depend on it.

PMID- 10894201
TI  - The Netherlands Institute for Accreditation of Hospitals.

PMID- 10894202
TI  - Outcome measures for complex regional pain syndrome type I: an overview in the
      context of the international classification of impairments, disabilities and
      handicaps.
AB  - PURPOSE: To determine the availability of relevant and objective outcome measures
      concerning complex regional pain syndrome type I (CRPS I) for rehabilitation
      medicine. METHOD: Outcome measures were classified according to the International
      Classification of Impairments, Disabilities and Handicaps. For each outcome
      measure a description of concept, operationalization into variables and
      instrument was given. We performed a PUBMED MEDLINE search (1980-1998) using the
      following keywords: complex regional pain syndrome, reflex sympathetic dystrophy,
      impairment, disability, handicap, (long-term) outcome and effect/efficacy.
      RESULTS: Most outcome measures were concentrated on impairments, whereas measures
      at the level of disabilities and handicaps, the most relevant levels for
      rehabilitation medicine, were mentioned in very few studies. Objective outcome
      measures were merely found at the level of impairment. CONCLUSION: The results
      indicate a need for the development of relevant outcome measures at the level of
      disabilities and handicaps that can objectively measure treatment efficacy for
      CRPS I.

PMID- 10894203
TI  - Experiences of siblings of children with physical disabilities: an empirical
      investigation.
AB  - PURPOSE: This study aimed to investigate the experiences of Dutch siblings of
      children with physical disabilities (n=43). METHOD: Interviews were conducted to
      investigate experiences of siblings in 3 areas: the sibling relationship, the
      relationship with parents, and the relationship with others. The siblings also
      completed a coping response inventory. RESULTS: The siblings reported
      difficulties in undertaking activities and in communicating with their
      brother/sister with a disability. Most siblings worried about the future and the
      health of their brother/sister with a disability. The siblings reported open
      communication and trust as the main characteristics of the relationship with
      their parents. They acknowledged their parents' attempts to treat all children
      equally, although parents were not always successful in doing so. Having a
      sibling with a disability did not cause problems in the relationship with
      friends. The awkward reactions of strangers caused the siblings much annoyance
      and distress. Siblings in this sample used more approach coping strategies than
      avoidance strategies, t(34) = 2.37, p < 0.05. CONCLUSION: The brothers and
      sisters generally did not experience many significant problems, however, a
      minority of the children did experience problems for which they would like help.
      In addition, they reported joys as well as problems.

PMID- 10894204
TI  - Sexuality in persons with lower extremity amputations.
AB  - PURPOSE: There is a paucity of information regarding sexual functioning in
      persons with lower extremity amputations. The purpose of this study was to
      describe sexual and psychological functioning and health status in persons with
      lower extremity amputation. METHODS: Self-report surveys assessed sexual
      functioning (Derogatis Inventory), depression (Beck Depression Inventory, anxiety
      (State-Trait Anxiety Inventory), and health status (Health Status Questionnaire)
      in a convenience sample of 30 men with lower extremity amputations. Mean age of
      the participants was 57 years (range 32-79). Mean duration since amputation was
      23 months (range 3-634 months). Twenty one subjects (70%) had trans-tibial and
      seven subjects (23%) had trans-femoral amputations. RESULTS: A majority of
      subjects were experiencing problems in several domains of sexual functioning.
      Fifty three percent (n = 16) of the subjects were engaged in sexual intercourse
      or oral sex at least once a month. Twenty seven percent (n = 8) were masturbating
      at least once a month. Nineteen subjects (63%) reported orgasmic problems and 67%
      were experiencing erectile difficulties. Despite these problems, interest in sex
      was high in over 90% of the subjects. There was no evidence of increased
      prevalence of depression or anxiety in these subjects when compared to other
      outpatient adult populations. CONCLUSIONS: Sexual problems were common in the
      subjects studied. Despite these problems, interest in sex remained high. Few
      investigations have been directed toward identifying the psychological and social
      factors that may contribute to these problems and more research with a larger
      population is needed in this area.

PMID- 10894205
TI  - Disability and quality of life in individuals with postpolio syndrome.
AB  - PURPOSE: The purpose of the study is to investigate disability and quality of
      life in individuals with the characteristic symptoms of postpolio syndrome.
      METHOD: Disability is assessed by means of the self-report activities of daily
      living instrument, and quality of life by means of Kaasa's questionnaire and the
      quality of life profile. RESULTS: The 39 subjects have on average lived with
      polio sequelae for 52 years. Their main difficulties are with moving, lifting and
      carrying. This means restricted mobility, sedentary activities and a need to
      prioritize. Half of them feel that polio has lessened their possibilities in
      life, and a quarter have still not accepted the limitations polio has involved.
      Nevertheless the majority report a high level of psychosocial well-being, and
      almost a quarter say that living with polio has meant personal development and
      strength. We found a significant correlation between on the one hand disability
      with regard to ambulation, arm strength and finger strength on the self-report
      ADL, and on the other hand the number of negative problems on the quality of life
      profile (0.33-0.45). CONCLUSION: The latter instrument needs further testing
      before its validity can be determined with certainty.

PMID- 10894206
TI  - The effectiveness of day treatment with persistently mentally ill in rural areas.
AB  - PURPOSE/METHOD: This study investigated the effectiveness of day treatment
      programmes in rural Minnesota by comparing 2 groups in terms of yearly rates of
      re-hospitalization. RESULTS: It was found that the group that responded
      positively to day treatment was much less likely to be re-hospitalized. Their
      rates of re-hospitalization were much lower than the state of Minnesota. The
      other group that dropped out of day treatment has a re-hospitalization rate as
      much as 10 times higher. CONCLUSION: This demonstrates the cost effectiveness of
      day treatment programmes.

PMID- 10894207
TI  - Can we exploit event-related potentials for retraining language after stroke?
AB  - PURPOSE: To ascertain the utility of event-related potentials in studying
      language processing in patients suffering from aphasia. METHODS: Recent methods
      to evaluate event related potentials in response to spoken words were applied in
      two young patients suffering from a recent aphasia in whom expressive deficits
      were particularly marked. Recordings were made on three occasions for each
      patient at the same time of the day. The second recording session took place
      after six months and the final one after one year. Eighteen right-handed subjects
      in normal health (10 women, 8 men) were enrolled as controls. RESULTS: Three
      kinds of potential were obtained over time, P300, P340 and N400. P300 was useful
      to monitor attention and discrimination. It improved over time. Both of our
      patients lacked a defined P340 potential, but longitudinal recordings could show
      a very slow reappearance over time although with a frequently inverted polarity.
      Apparently, the expressive aphasia did not improve over a one year interval. In
      contrast to P340, N400 was relatively preserved. This potential is linked to
      semantic judgement. The patients with relatively preserved comprehension were
      able to exhibit a N400 soon after stroke. The bilateral representation indicated
      that the right hemisphere was involved in some kind of language processing.
      CONCLUSION: The results indicate that digitized spoken words appear to be an
      appropriate tool because they permit the study of EEG changes on a millisecond-to
      millisecond basis. Apparently, ERPs enable us to study receptive processes in
      patients with expressive aphasia. Moreover, they appear to be particularly
      suitable for monitoring the recovery of neural mechanisms responsible for
      language.

PMID- 10894208
TI  - Coiling, clipping, or medical management of unruptured intracranial aneurysms:
      time to randomize?

PMID- 10894209
TI  - How does botulinum toxin work?

PMID- 10894210
TI  - Gene therapy for Canavan disease?

PMID- 10894211
TI  - Endovascular and surgical treatment of unruptured cerebral aneurysms: comparison
      of risks.
AB  - Unruptured cerebral aneurysms are commonly treated by surgical clipping, but
      endovascular coil embolization is increasingly employed as an alternative. In a
      blinded review of unruptured aneurysms treated at our institution since 1990, we
      identified patients whose aneurysms were judged to be treatable by both
      neurosurgeons and neurointerventional radiologists. A change in Rankin Scale
      score of 2 or more from hospital admission to discharge, indicating a new
      moderate disability or worse, was predefined as the primary outcome measure. Long
      term follow-up was obtained by mailed questionnaire and telephone interview.
      Length of stay and hospital charges were totaled for all hospitalizations,
      including follow-up. Sixty-eight patients treated surgically and 62 patients
      treated with endovascular coil embolization were considered candidates for either
      procedure on blinded review, and overall anticipated procedure risk was rated as
      identical. A larger proportion of patients in the surgical group developed a
      change in Rankin Scale score of 2 or more (25% of surgical patients vs 8% of
      endovascular patients). Total length of stay was longer (mean days: 7.7 for
      surgical patients vs 5.0 for endovascular patients) and hospital charges were
      greater (mean, $38,000 for surgical patients vs $33,400 for endovascular
      patients) for the surgical patients. At follow-up, an average of 3.9 years after
      the procedure, surgical patients were more likely to report persistent new
      symptoms or disability since treatment (34% of surgical patients vs 8% of
      endovascular patients) and a longer period for recovery to normal (50% returning
      to normal in 1 year for surgery and in 27 days for coil embolization). Coil
      embolization of unruptured cerebral aneurysms seems to be associated with
      significantly fewer complications than surgical clipping. More long-term data on
      aneurysm rupture rates are required to confirm efficacy.

PMID- 10894212
TI  - Effects of botulinum toxin type A on intracortical inhibition in patients with
      dystonia.
AB  - To find out whether botulinum toxin alters the excitability of cortical motor
      areas, we studied intracortical inhibition with transcranial magnetic stimulation
      in patients with upper limb dystonia before, 1 month after, and 3 months after
      the injection of botulinum toxin type A in the affected muscles. Eleven normal
      subjects and 12 patients with dystonia involving the upper limbs (7 with
      generalized dystonia, 2 with segmental dystonia, and 3 with focal dystonia) were
      studied. Patients were assessed clinically with the Dystonia Movement Scale.
      Paired magnetic stimuli were delivered by two Magstim 200 magnetic stimulators
      connected through a Bistim module to a figure-of-eight coil placed over the motor
      area of the forearm muscles. Paired stimulation was given at rest. A subthreshold
      (80% of motor threshold) conditioning stimulus was delivered 3 and 5 msec before
      the suprathreshold (120% of motor threshold) test stimulus. Electromyographic
      signals were recorded over the flexor or extensor muscles of the forearm on the
      affected side. We measured the amplitude of the test motor evoked potential
      (expressed as a percentage of the unconditioned motor evoked potential). All
      results were compared using ANOVA. In all patients, a botulinum toxin type A
      injection (50-100 mouse units) reduced dystonic movements in the arm. In normal
      subjects, electromyographic recordings showed significant inhibition of the test
      response. Before botulinum toxin injection, patients had less test response
      inhibition than normal subjects. One month after injection, patients had test
      response inhibition similar to that of normal subjects. At 3 months after
      injection, they again had less inhibition than normal subjects or patients at 1
      month after injection. In conclusion, our data suggest that botulinum toxin can
      transiently alter the excitability of the cortical motor areas by reorganizing
      the inhibitory and excitatory intracortical circuits. The cortical changes
      probably originate through peripheral mechanisms.

PMID- 10894213
TI  - Aspartoacylase gene transfer to the mammalian central nervous system with
      therapeutic implications for Canavan disease.
AB  - With the ultimate goal of developing safe and effective in vivo gene therapy for
      the treatment of Canavan disease and other neurological disorders, we developed a
      non-viral lipid-entrapped, polycation-condensed delivery system (LPD) for central
      nervous system gene transfer, in conjunction with adeno-associated virus (AAV)
      based plasmids containing recombinant aspartoacylase (ASPA). The gene delivery
      system was tested in healthy rodents and primates, before proceeding to
      preliminary studies in 2 children with Canavan disease. Toxicity and expression
      testing was first carried out in human 293 cells, which demonstrated effective
      transduction of cells and high levels of functional ASPA activity. We performed
      in vivo toxicity and expression testing of LPD/pAAVaspa and LPD/pAAVlac in
      rodents, which demonstrated widespread gene expression for more than 10 months
      after intraventricular delivery, and local expression in deep brain nuclei and
      white matter tracts for more than 6 months after intraparenchymal injections,
      with no significant adverse effects. We also performed intraventricular delivery
      of LPD/pAAVaspa to 2 cynomologous monkeys, with 2 additional monkeys receiving
      LPD and saline controls. None of the monkeys demonstrated significant adverse
      effects, and at 1 month the 2 LPD/pAAVaspa monkeys were positive for human ASPA
      transcript by reverse transcriptase polymerase chain reaction of brain tissue
      punches. Finally, we performed the first in vivo gene transfer study for a human
      neurodegenerative disease in 2 children with Canavan disease to assess the in
      vivo toxicity and efficacy of ASPA gene delivery. Our results suggest that
      LPD/pAAVaspa is well tolerated in human subjects and is associated with
      biochemical, radiological, and clinical changes.

PMID- 10894214
TI  - Familial perisylvian polymicrogyria: a new familial syndrome of cortical
      maldevelopment.
AB  - Two familial X-linked dominant syndromes of cortical maldevelopment have recently
      been described: double cortex/lissencephaly syndrome and bilateral
      periventricular nodular heterotopia. We report on 12 kindreds with familial
      perisylvian polymicrogyria (FPP) presenting at 10 centers, examine the clinical
      presentation in these familial cases, and propose a possible mode of inheritance.
      The clinical and radiological pattern was variable among the 42 patients, with
      clinical differences among the families and even within members of the same
      family. Pseudobulbar signs, cognitive deficits, epilepsy, and perisylvian
      abnormalities on imaging studies were not found in all patients. When present,
      they displayed a spectrum of severity. The only clear correlation in this study
      was between bilateral imaging findings and abnormal tongue movements and/or
      pronounced dysarthria. Most of the families provided evidence suggestive of, or
      compatible with, X-linked transmission. On the other hand, the pedigrees of 2
      families ruled out X-linked inheritance. The most likely mode of inheritance for
      these 2 families was autosomal dominant with decreased penetrance; however,
      autosomal recessive inheritance with pseudodominance could not be ruled out in 1
      family. We conclude that FPP appears to be genetically heterogeneous. However,
      most of the families probably represent a third previously undescribed X-linked
      syndrome of cortical maldevelopment.

PMID- 10894215
TI  - Sympathetic innervation and function in reflex sympathetic dystrophy.
AB  - Patients with reflex sympathetic dystrophy have posttraumatic pain
      disproportionate to the injury and spreading beyond the distribution of any
      single peripheral nerve. We examined sympathetic neurocirculatory function and
      the role of sympathetic postganglionic nerve traffic in maintaining the pain in
      30 patients with reflex sympathetic dystrophy. Most had had the condition for
      more than 1 year, and 14 had undergone sympathectomy for the pain. Positron
      emission tomographic scanning after administration of 13N-ammonia was used to
      assess local perfusion, and 6-[18F]fluorodopamine was used to assess sympathetic
      innervation. Rates of entry of norepinephrine in the regional venous drainage
      (spillovers) and regional plasma levels of L-dihydroxyphenylalanine (the
      immediate product of the rate-limiting enzymatic step in norepinephrine
      biosynthesis) and dihydroxyphenylglycol (the main neuronal metabolite of
      norepinephrine) were measured with and without intravenous trimethaphan for
      ganglion blockade. 13N-Ammonia-derived radioactivity was less on the affected
      side than on the unaffected side, whereas 6-[18F]fluorodopamine-derived
      radioactivity was symmetrical. Thus, perfusion-adjusted 6-[18F]fluorodopamine
      derived radioactivity was higher on the affected side. Norepinephrine spillover
      and arteriovenous increments in plasma levels of L-dihydroxyphenylalanine and
      dihydroxyphenylglycol did not differ significantly between affected and
      unaffected limbs, although 4 patients had noticeably less norepinephrine
      spillover and smaller arteriovenous increments in plasma dihydroxyphenylglycol on
      the affected side. Trimethaphan decreased the pain in only 2 of 12
      nonsympathectomized patients. The results indicate that patients with chronic
      unilateral reflex sympathetic dystrophy have decreased perfusion of the affected
      limb, symmetrical sympathetic innervation and norepinephrine synthesis, variably
      decreased release and turnover of norepinephrine in the affected limb, and
      failure of ganglion blockade to improve the pain in most cases. These findings
      suggest augmented vasoconstriction, intact sympathetic terminal innervation,
      possibly impaired sympathetic neurotransmission, and pain usually independent of
      sympathetic neurocirculatory outflows.

PMID- 10894216
TI  - Visual impairment in children with epilepsy treated with vigabatrin.
AB  - Vigabatrin is an anti-epileptic drug particularly useful for drug-resistant
      partial seizures and infantile spasms. Recently, vigabatrin-induced visual field
      constriction (VFC) and abnormal ocular electrophysiological studies were
      reported. In this study, we assessed visual fields, visual evoked potentials
      (VEPs), and electroretinography (ERG) in children treated with vigabatrin. Twenty
      four visually asymptomatic children underwent a clinical ophthalmological
      examination, perimetry when appropriate, and VEP and ERG. Thirteen patients had
      at least one abnormal study. VFC was seen in 11 of 17 patients who had perimetry;
      5 of 15 patients who underwent VEP testing and 4 of 11 who underwent ERG testing
      had abnormal examinations. For the most part, abnormal VEPs and ERGs were found
      in children who also had VFC. There was a consistent trend for longer treatment
      periods to correlate with VFC, abnormal ERGs, and VEPs. In summary, over half of
      the children treated with vigabatrin demonstrated VFC or abnormal ocular
      electrophysiological studies. Perimetry seemed to be the most sensitive modality
      for identifying vigabatrin toxicity. Abnormal ERGs and VEPs were primarily seen
      in children with VFC and may be useful in monitoring children who are not
      appropriate candidates for perimetry. Although the incidence of vigabatrin
      induced VFC is worrisome, in the context of intractable seizures or infantile
      spasms, therapeutic benefits must be weighed against risks.

PMID- 10894217
TI  - Parkin deletions in a family with adult-onset, tremor-dominant parkinsonism:
      expanding the phenotype.
AB  - A gene for autosomal recessive parkinsonism, PARK2 (parkin), has recently been
      identified on chromosome 6q and shown to be mutated in Japanese and European
      families, mostly with early-onset parkinsonism. Here we present a large pedigree
      from South Tyrol (a region of northern Italy) with adult-onset, clinically
      typical tremor-dominant parkinsonism of apparently autosomal dominant
      inheritance. Haplotype analysis excluded linkage to the chromosome 2p, 4p, and 4q
      regions that harbor genes associated with autosomal dominant parkinsonism, but
      implicated the parkin locus on chromosome 6q. Compound heterozygous deletions in
      the parkin gene (one large and one truncating) were identified in 4 affected male
      siblings. The patients were clinically indistinguishable from most patients with
      idiopathic Parkinson's disease. None of them displayed any of the clinical
      hallmarks described in patients with previously reported parkin mutations,
      including diurnal fluctuations, benefit from sleep, foot dystonia, hyperreflexia,
      and early susceptibility to levodopa-induced dyskinesias. Two affected female
      individuals carried one (truncating) of the two deletions in a heterozygous state
      with an apparently normal allele. We conclude that the phenotypic spectrum
      associated with mutations in the parkin gene is broader than previously reported,
      suggesting that this gene may be important in the etiology of the more frequent
      late-onset typical Parkinson's disease.

PMID- 10894218
TI  - Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and
      dentatorubropallidoluysian atrophy.
AB  - We studied in vivo muscle energy metabolism in patients with Huntington's disease
      (HD) and dentatorubropallidoluysian atrophy (DRPLA) using 31P magnetic resonance
      spectroscopy (MRS). Twelve gene-positive HP patients (4 presymptomatic patients)
      and 2 gene-positive DRPLA patients (1 presymptomatic patient) were studied. 31P
      MRS at rest showed a reduced phosphocreatine-to-inorganic phosphate ratio in the
      symptomatic HD patients and DRPLA patient. Muscle adenosine
      triphosphate/(phosphocreatine + inorganic phosphate) at rest was significantly
      reduced in both groups of symptomatic and presymptomatic HD subjects and was
      below the normal range in the 2 DRPLA subjects. During recovery from exercise,
      the maximum rate of mitochondrial adenosine triphosphate production was reduced
      by 44% in symptomatic HD patients and by 35% in presymptomatic HD carriers. The
      maximum rate of mitochondrial adenosine triphosphate production in muscle was
      also reduced by around 46% in the 2 DRPLA subjects. Our findings show that HD and
      DRPLA share a deficit of in vivo mitochondrial oxidative metabolism, supporting a
      role for mitochondrial dysfunction as a factor involved in the pathogenesis of
      these polyglutamine repeat-mediated neurodegenerative disorders. The
      identification of 31P-MRS abnormalities may offer a surrogate biochemical marker
      by which to study disease progression and the effects of treatment in HD and
      DRPLA.

PMID- 10894219
TI  - Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1
      neurons.
AB  - The pathogenesis of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) is
      poorly understood, but changes in the expression of specific messenger RNAs
      (mRNAs) may reflect mechanisms underlying the formation of NFTs and their
      consequences in affected neurons. For these reasons, we compared the relative
      abundance of multiple mRNAs in tangle-bearing versus normal CA1 neurons aspirated
      from sections of AD and control brains. Amplified antisense RNA expression
      profiling was performed on individual isolated neurons for analysis of greater
      than 18,000 expressed sequence tagged complementary DNAs (cDNAs) with cDNA
      microarrays, and further quantitative analyses were performed by reverse Northern
      blot analysis on 120 selected mRNAs on custom cDNA arrays. Relative to normal CA1
      neurons, those harboring NFTs in AD brains showed significant reductions in
      several classes of mRNAs that are known to encode proteins implicated in AD
      neuropathology, including phosphatases/kinases, cytoskeletal proteins, synaptic
      proteins, glutamate receptors, and dopamine receptors. Because cathepsin D mRNA
      was upregulated in NFT-bearing CA1 neurons in AD brains, we performed
      immunohistochemical studies that demonstrated abundant cathepsin D
      immunoreactivity in the same population of tangle-bearing CA1 neurons. In
      addition, levels of mRNAs encoding proteins not previously implicated in AD were
      reduced in CA1 tangle-bearing neurons, suggesting that these proteins (eg,
      activity-regulated cytoskeleton-associated protein, focal adhesion kinase,
      glutaredoxin, utrophin) may be novel mediators of NFT formation or degeneration
      in affected neurons. Thus, the profile of mRNAs differentially expressed by
      tangle-bearing CA1 neurons may represent a "molecular fingerprint" of these
      neurons, and we speculate that mRNA expression profiles of diseased neurons in AD
      may suggest new directions for AD research or identify novel targets for
      developing more effective AD therapies.

PMID- 10894220
TI  - Is epileptogenic cortex truly hypometabolic on interictal positron emission
      tomography?
AB  - Positron emission tomography (PET) of glucose metabolism is often applied for the
      localization of epileptogenic brain regions, but hypometabolic areas are often
      larger than or can miss epileptogenic cortex in nonlesional neocortical epilepsy.
      The present study is a three-dimensional brain surface analysis designed to
      demonstrate the functional relation between glucose PET abnormalities and
      epileptogenic cortical regions. Twelve young patients (mean age, 10.8 years) with
      intractable epilepsy of neocortical origin underwent chronic intracranial
      electroencephalographic monitoring. The exact location of the subdural electrodes
      was determined on high-resolution three-dimensional reconstructed magnetic
      resonance imaging scan volumes. The electrodes were classified according to their
      locations over cortical areas, which were defined as hypometabolic,
      normometabolic, or at the border between hypometabolic and normal cortex
      (metabolic "border zones") based on interictal glucose PET. Electrodes with
      seizure onset were located over metabolic border zones significantly more
      frequently than over hypometabolic or normometabolic regions. Seizure spread
      electrodes also more frequently overlay metabolic border zones than hypometabolic
      regions. These findings suggest that cortical areas with hypometabolism should be
      interpreted as regions mostly not involved in seizure activity, although
      epileptic activity commonly occurs in the surrounding cortex. This feature of
      hypometabolic cortex is remarkably similar to that of structural brain lesions
      surrounded by epileptogenic cortex. Cortical areas bordering hypometabolic
      regions can be highly epileptogenic and should be carefully assessed in
      presurgical evaluations.

PMID- 10894221
TI  - Neuronal loss in Onuf's nucleus in three patients with progressive supranuclear
      palsy.
AB  - Disorders of micturition have been reported only sporadically in patients with
      progressive supranuclear palsy (PSP). We report the results of a
      clinicopathological study of 3 patients with a definite diagnosis of PSP at
      various stages of their illness with sphincter abnormalities. Electromyography of
      the sphincter muscles was performed in all 3 patients and was abnormal in 2.
      Morphological and morphometric evaluation of Onuf's nucleus in the sacral spinal
      cord, which is involved in sphincter control, showed severe cell loss, presence
      of neurofibrillary tangles, neuropil threads, and glial inclusions. We conclude
      that bladder dysfunction and abnormal sphincter electromyographic results are due
      to pathological changes in Onuf's nucleus, and we propose that sphincter
      abnormalities should be included in the list of possible symptoms of PSP.

PMID- 10894222
TI  - Leigh disease caused by the mitochondrial DNA G14459A mutation in unrelated
      families.
AB  - Leigh disease can be caused by defects of both nuclear and mitochondrially
      encoded genes. One mitochondrial DNA mutation, G14459A, has been associated with
      both respiratory chain complex I deficiency and Leber's hereditary optic
      neuropathy, with or without dystonia. Here, we report the occurrence of this
      mutation in 3 complex I-deficient patients from 2 separate pedigrees who
      presented with Leigh disease, with no evidence or family history of Leber's
      hereditary optic neuropathy or dystonia.

PMID- 10894223
TI  - [18F]fluorodeoxyglucose positron emission tomography in the diagnosis of cancer
      in patients with paraneoplastic neurological syndrome and anti-Hu antibodies.
AB  - The diagnosis of cancer is often difficult in patients with paraneoplastic
      neurological syndrome and anti-Hu antibodies. Fluorodeoxyglucose 18 positron
      emission tomography scanning is a highly sensitive and specific method to detect
      lung tumors. We investigated 15 patients with paraneoplastic neurological
      syndrome and anti-Hu antibodies. Radiological methods led to the diagnosis of
      cancer in 12 patients, and test results were negative in 3. Whole-body
      [18F]fluorodeoxyglucose positron emission tomography showed abnormal uptake in
      the mediastinum in these 3 patients in accordance with the expected location of
      the malignancy.

PMID- 10894224
TI  - Linkage of autosomal recessive hereditary spastic paraplegia with mental
      impairment and thin corpus callosum to chromosome 15A13-15.
AB  - To date, three loci for autosomal recessive hereditary spastic paraplegia (ARHSP)
      linked to chromosomes 8p12-q13, 16qter, and 15q13-15 have been characterized. We
      have clinically characterized 13 Japanese ARHSP families and performed genetic
      linkage analyses. All 13 families were classified as having the "complicated"
      form, which manifests with mental impairment and thin corpus callosum. Linkage to
      the 8p12-q13 and 16qter loci was excluded, although 10 of the 13 families showed
      marker data consistent with linkage to the 15q13-15 locus. The multipoint LOD
      score of the 10 families linked to chromosome 15 was above 9.00 in the 3
      centimorgan segment flanked by D15S994 and D15S659, with a maximum multipoint LOD
      score of 9.68 at a position 1.2 centimorgans telomeric from D15S994 to D15S659.
      We have shown that ARHSP with thin corpus callosum, a subtype of recessive
      spastic paraplegia, maps to chromosome 15q13-15.

PMID- 10894225
TI  - Multifocal or generalized tonic dystonia of complex regional pain syndrome: a
      distinct clinical entity associated with HLA-DR13.
AB  - We report on 26 patients with a distinct phenotype of complex regional pain
      syndrome that progressed toward a multifocal or generalized tonic dystonia. The
      dystonia initiated distally, involved mainly flexor muscles, and was associated
      with sensory and autonomic symptoms. Dryness of the eyes or mouth and bladder and
      bowel disturbances were frequently reported. There was no increase in the
      familial prevalence of autoimmune-mediated diseases. Compared with controls, a
      significant elevation of HLA-DR13 was found in the patients. Thus, HLA-DR13 may
      be a factor indicating susceptibility to this distinct phenotype of complex
      regional pain syndrome.

PMID- 10894226
TI  - Dual epileptic foci in a single patient express distinct temporal patterns
      dependent on limbic versus nonlimbic brain location.
AB  - How timing information is transferred from the suprachiasmatic nucleus to other
      regions of the brain to mediate activity, either physiological or pathological,
      is largely unclear. A patient with medically refractory epilepsy and a well
      documented, long-term seizure diary provided a unique means to demonstrate how
      susceptibility to chronobiological modulation varies with brain region.
      Evaluation for epilepsy surgery disclosed two independent epileptic foci, one
      limbic and the other nonlimbic. Seizures from both foci occurred periodically
      with a dominant period of 24 hours but were out of phase with each other.
      Temporal lobe seizures occurred maximally in the light portion of the daily light
      dark cycle, and parietal lobe seizures occurred nocturnally and out of phase with
      limbic seizures. These data suggest that neuronal excitation and inhibition,
      depending on the anatomical system involved in epilepsy, may be differently
      affected by circadian modulation.

PMID- 10894227
TI  - Pipecolic acid elevation in plasma and cerebrospinal fluid of two patients with
      pyridoxine-dependent epilepsy.
AB  - Diagnosis of pyridoxine-dependent epilepsy is based on the clinical response to
      high-dosage application of pyridoxine. Here, we report on 2 patients with
      pyridoxine-dependent epilepsy with significant elevation of pipecolic acid
      concentrations in plasma and cerebrospinal fluid (CSF) and further increase of
      pipecolic acid in CSF during a 72-hour pyridoxine withdrawal in 1 of them.
      Patients with non-pyridoxine-dependent epilepsy had normal pipecolic acid
      concentrations in plasma and significantly lower concentrations in CSF. High
      plasma and CSF pipecolic acid concentrations might provide a diagnostic marker in
      pyridoxine-dependent epilepsy.

PMID- 10894228
TI  - FTDP-17: phenotypical heterogeneity within P301S.

PMID- 10894229
TI  - Association studies of Parkinson's disease and parkin polymorphisms.

PMID- 10894230
TI  - Inflammatory changes in the substantia nigra and striatum following MPTP
      intoxication.

PMID- 10894231
TI  - D2 dopamine receptor gene in myoclonic dystonia and essential myoclonus.

PMID- 10894232
TI  - Brain redundancy: responsivity or plasticity?

PMID- 10894233
TI  - Weight loss in Huntington's disease.

PMID- 10894234
TI  - Recessive PMP22 mutations: quantitative and qualitative aspects.

PMID- 10894235
TI  - Standardized burn model using a multiparametric histologic analysis of burn
      depth.
AB  - OBJECTIVE: Burn depth and extent determine prognosis and therapy. The current
      classification into first-, second-, and third-degree burns is crude, making
      comparisons between studies difficult. The authors standardized a reproducible
      burn model and a precise histopathologic method for describing burn depth in
      swine. METHODS: This was a prospective, cross-sectional interventional animal
      study. Eighteen paired sets of burns were inflicted on the clipped flank skin of
      two anesthetized domestic pigs with a 2.5 cm by 2.5 cm by 7.5 cm aluminum bar
      preheated in water to 50 degrees C, 60 degrees C, 70 degrees C, 80 degrees C, 90
      degrees C, degrees C or 100 degrees C. The bar was applied for 10, 20, or 30
      seconds. Full-thickness skin biopsies were obtained 30 minutes after injury for
      blinded histopathologic evaluation using hematoxylin and eosin staining. Two
      dermatopathologists made two sets of measurements and were masked to each other's
      evaluations. The depth of injury was measured with an ocular microtome for each
      of five dermal parameters: collagen discoloration, intercollagen basophilic
      material, endothelial cell necrosis, epithelial cell necrosis, and mesenchymal
      cell necrosis. The correlation between burn depths of the paired sets of
      experiments was calculated to assess the reliability of the model. Inter- and
      intraobserver correlations were calculated to assess the reliability of the
      scale. Analysis of variance (ANOVA) was used to assess the relation between
      temperature and exposure times on burn depth. RESULTS: Depth of injury for all
      five dermal elements was related to temperature and exposure times (ANOVA, p <
      0.001 for each). The depth of injury in the paired sets of burns was highly
      consistent (Pearson correlation, range = 0.88-0.95). Inter- and intraobserver
      correlations were excellent for all measured elements (range = 0.91-0.97 and 0.95
      0.99, respectively). CONCLUSIONS: The authors describe a simple and reproducible
      animal burn model and histopathologic scale for measuring burn depth that they
      believe will facilitate standardization and comparison within future burn
      studies.

PMID- 10894236
TI  - Effects of alcohol on the geographic variation of driver fatalities in motor
      vehicle crashes.
AB  - OBJECTIVE: To determine whether the increased risk of dying in a rural vs
      nonrural motor vehicle crash (MVC) can be attributed to driver demographics,
      crash characteristics, or police-reported alcohol use. METHODS: A retrospective
      cohort study was conducted, comparing all rural (116,242) and a 20% random sample
      of nonrural (104,197) Michigan drivers involved in an MVC during 1994-1996. Data
      consisted of all police-reported traffic crashes on public roadways. A logistic
      regression model was created, using survival as the dependent variable and
      gender, age, crash characteristics, and rural or nonrural county as independent
      variables. Driver alcohol use, as reported by the investigating officer, was
      introduced into the model, and the effect was analyzed. RESULTS: Nonsurvivors
      represented 0.2% of the total; 99.8% were survivors. Police-reported alcohol use
      was reported for 3.9% of drivers. Drivers in rural MVCs were more likely to be
      male, to be more than 50 years of age, to have been drinking alcohol, and to have
      more severe vehicle deformation as a result of the MVC. The relative risk (RR)
      for MVC nonsurvivors was 1.69 [95% confidence interval (CI) = 1.3 to 2.1] times
      higher for drivers in rural than nonrural counties. After adjusting for
      demographic and crash characteristics, the RR was 1.56 (95% CI = 1.2 to 1.9).
      Controlling for alcohol and its interactions decreased the RR to 1.26 (95% CI =
      0.6 to 2.4), a nonsignificant difference between rural and nonrural MVC
      mortalities. CONCLUSIONS: Alcohol use by drivers in Michigan was a significant
      contributor for nonsurvivors of rural crashes. Efforts to decrease rural MVC
      mortality must address alcohol use.

PMID- 10894237
TI  - Alcoholism in the emergency department: an epidemiologic study.
AB  - OBJECTIVE: To describe the epidemiology of alcoholism in ED patients. METHODS:
      Over a two-month period, every adult patient brought by ambulance to the ED of a
      large municipal hospital was prospectively enrolled by questionnaire. Data
      collected included demographics, previous ED use, triage complaint-related
      diagnoses, hospital admission rates, and ethanol levels (if determined). The CAGE
      alcoholism questions were administered to all patients by trained assistants. The
      only exclusion criterion was the inability to communicate while in the ED. A chi
      square analysis was used to compare categorical variables. RESULTS: A total of
      2,658 patients were enrolled in the study; 226 were unable to respond to the CAGE
      questions. Five hundred eighty-eight of the remaining 2,432 patients (24%) were
      defined as being alcoholic by an affirmative response to at least two of the CAGE
      questions. All four questions were answered affirmatively by 17% of the total
      patients. Alcoholic patients were more likely to be male (88% vs 60%), unemployed
      (87% vs 71%), undomiciled (46% vs 20%), polysubstance users (52% vs 25%), and
      tobacco users (77% vs 41%), and to have had an ED visit in the previous six
      months (51% vs 35%) (p < 0.001 for all tests). Ethanol levels ranged from zero to
      573 mg/dL. Whereas no positive response to a single CAGE question was predictive
      of a final diagnosis of alcoholism, a blood ethanol level more than 300 mg/dL
      predicted an affirmative response to at least two CAGE questions in 97% of cases.
      CONCLUSIONS: Alcoholism should be presumed to be present in a substantial number
      of patients who present to urban EDs by ambulance.

PMID- 10894238
TI  - Setting-based practice variation in the management of simple febrile seizure.
AB  - OBJECTIVE: To identify provider-based differences in the ED assessment and
      management of children presenting with uncomplicated, first-time febrile
      seizures. METHODS: Multicenter, retrospective cohort study of seven EDs in-the
      Chicago area: two tertiary academic pediatric EDs (PEDs) and five community-based
      general EDs (GEDs). The visits of all patients with a discharge diagnosis
      including the term "seizure" were identified from a 30-month period. Records of
      patients who met criteria for simple, first-time febrile seizure were reviewed
      (age 6-60 months; temperature > or =38.0 degrees C; single, generalized, tonic
      clonic seizure <20 minutes; "alert" or "arousable" on presentation; absence of
      known neurologic disease). RESULTS: Four hundred fifty-five records were
      included: 330 and 125 patients presenting to GEDs and PEDs, respectively. The two
      groups did not differ in mean age, vital signs, reported duration of seizure, or
      prior antibiotic use. Lumbar puncture (LP) was performed more often in the GED
      group (33% vs 22%). No patients were found to have bacterial meningitis. The
      patients in the GED group were more likely to receive parenteral antibiotics in
      the ED (56% vs 22%) and to be admitted or transferred (18% vs 4%). In a logistic
      regression model incorporating age, temperature, seizure duration, seizure in the
      ED, prior antibiotic use, primary care, and insurance status, the GED patients
      remained more likely to have an LP (OR 1.5), receive parenteral antibiotics (OR
      2.5), and be admitted or transferred (OR 2.5). CONCLUSIONS: There were
      significant setting-based differences in the evaluation and management of
      children with simple febrile seizures presenting to GEDs and PEDs.

PMID- 10894239
TI  - Predicting recovery from acute asthma in an emergency diagnostic and treatment
      unit.
AB  - OBJECTIVE: Optimal use of emergency diagnostic and treatment unit (EDTU)
      resources for treatment of acute asthma should be facilitated by the selection of
      patients with a high probability of discharge from the EDTU. The study goal was
      to identify characteristics of the patient or exacerbation that could be used to
      predict recovery of pulmonary function within 12 hours. METHODS: Comprehensive
      cohort design in an urban public hospital. The subjects were 269 patients with
      moderately severe asthma exacerbations. Data were collected for historical and
      presenting features and response to treatment over 12 hours. Two outcomes were
      examined: 1) discharge from the EDTU and 2) achieving 50% predicted peak
      expiratory flow rate (PEFR) within 12 hours. RESULTS: The two outcomes showed
      good concordance. The third-treatment PEFR was found to be predictive of both
      discharge and reaching 50% predicted PEFR within 12 hours. Since the objective
      measure of reaching 50% predicted PEFR is more readily defined and thus more
      generalizable, the authors focused on this outcome when describing prediction
      zones. Patients with 40% or higher PEFR after third treatment had an 89%
      probability of reaching 50% predicted in 12 hours, while those with a third
      treatment PEFR lower than 32% predicted had only a 22% probability. CONCLUSIONS:
      A simple objective measure of pulmonary function early in treatment discriminated
      among those with high, low, and intermediate probabilities of achieving a
      specified level of PEFR within 12 hours. Awareness of this probability could
      assist clinicians attempting to predict discharge from the EDTU and facilitate
      decision making regarding utilization of EDTU resources.

PMID- 10894240
TI  - Repeat ambulance use by pediatric patients.
AB  - OBJECTIVE: To compare pediatric patients transported by ambulance on more than
      one occasion (repeat) with those transported only once. METHODS: The authors
      analyzed pediatric (patient < 21 years old) transports for 1992-1995 by the
      ambulance service that provides 99% of transports for a non-innercity
      metropolitan area. Repeat transports were compared with single transports with
      regard to patient age, gender, chief complaint, and payment source. RESULTS:
      There were 17,448 transports involving 15,168 patients. Nearly half (49.0%) of
      the repeat transports involved patients in the oldest age category, 17 to 20.9
      years, contrasted with 38.0% of single transports (p < 0.00001). Females
      comprised 51.4% of the repeat transports and 48.5% of the single transports (p =
      0.0008). Traumatic complaints accounted for one-third (33.0%) of the repeat
      transports and half (51.1%) of the single transports (p < 0.0001). Chief
      complaints of the patients with repeat transports were more likely to be seizure,
      assault, abdominal pain, and respiratory problems, and less likely to be falls
      and motor vehicle-related complaints, than chief complaints of the patients with
      single transports (p < 0.0001). More than one-third (39.0%) of the repeat
      transports were funded by Medicaid, in contrast with 19.8% of the single
      transports (p < 0.0001). CONCLUSIONS: Compared with single transports, repeat
      transports were more likely to involve patients more than 16 years of age,
      female, and with a chief complaint of seizure, assault, abdominal pain, or
      respiratory distress, and more likely to be funded by public insurance
      (Medicaid). Repeat pediatric transports warrant further investigation. This
      information may be useful in designing interventions targeted at reducing
      emergencies and hence ambulance use.

PMID- 10894241
TI  - Association of naphthalene with acute hemolytic anemia.
AB  - OBJECTIVES: To describe the prevalence and severity of naphthalene-associated
      hemolysis (NA1) and infection-associated hemolysis (IAH) in children with glucose
      6-phosphate dehydrogenase (G6-PD) deficiency. To survey the rationale for
      naphthalene-containing moth repellent (mothball) use in the study population and
      to compare this with that of a more diverse population. METHODS: A ten-year
      retrospective chart review of 160 patients with G-6-PD deficiency and/or anemia
      and an analysis of 24 hospitalized African-American children with an episode of
      acute hemolysis associated with G-6-PD deficiency were conducted. The parents of
      330 children cared for in the pediatric emergency departments (EDs) of two
      tertiary care centers were questioned regarding domestic mothball (naphthalene)
      use. RESULTS: Fourteen of 24 (58.3%) of the children identified with G-6-PD
      deficiency presented with hemolysis associated with exposure to naphthalene
      containing moth repellents. The remaining ten had IAH. Seventy-nine percent of
      the NAH group required transfusion, compared with 60% of the IAH group. Mothballs
      were reportedly used by 27% of the families surveyed in one inner-city population
      with a 2-13% incidence of G-6-PD deficiency and by 15% in a more culturally
      diverse city. The main reported motivation for use was the fresh scent, not as a
      moth repellent. CONCLUSIONS: Mothballs are used for previously unrecognized
      reasons. Naphthalene-containing mothballs can pose a hematologic threat to
      vulnerable populations.

PMID- 10894242
TI  - Public expectations of survival following cardiopulmonary resuscitation.
AB  - Previous studies have demonstrated that the public maintains unrealistic
      expectations of the potential for successful recovery following administration of
      cardiopulmonary resuscitation (CPR). Others have attributed this phenomenon to
      misrepresentation of CPR outcomes on television and other sources of public
      information. OBJECTIVES: To determine public expectations of CPR and correlate
      these expectations with various sources of information regarding CPR, including
      age, television, personal medical training, public programs, friends/family with
      medical training, and personal experience with CPR. METHODS: A written survey was
      randomly distributed to local church congregations and completed on a voluntary
      basis. RESULTS: Ninety-six percent of the respondents expected CPR to be
      unrealistically effective. Those factors found to increase predicted CPR survival
      rate were as follows: 1) being under 50 years of age, 2) use of television as a
      source of information regarding CPR, 3) personal medical training, and 4) use of
      public programs about CPR. Neither exposure to friends or family with medical
      training nor personal experience with CPR resulted in increased CPR survival
      predictions. CONCLUSIONS: Regardless of the source, the public is not accurately
      informed about the effectiveness of CPR. This creates a situation in which people
      may elect CPR for themselves or for family members when survival, not to mention
      recovery, is unlikely. Without dissemination of realistic statistics regarding
      survival and recovery following CPR, the public will maintain unrealistic
      expectations of CPR, and be unable to make well-informed decisions concerning its
      use.

PMID- 10894243
TI  - Selection criteria for emergency medicine residency applicants.
AB  - OBJECTIVES: To determine the criteria used by emergency medicine (EM) residency
      selection committees to select their residents, to determine whether there is a
      consensus among residency programs, to inform programs of areas of possible
      inconsistency, and to better educate applicants pursuing careers in EM. METHODS:
      A questionnaire consisting of 20 items based on the current Electronic Residency
      Application Service (ERAS) guidelines was mailed to the program directors of all
      118 EM residencies in existence in February 1998. The program directors were
      instructed to rank each item on a five-point scale (5 = most important, 1 = least
      important) as to its importance in the selection of residents. Followup was done
      in the form of e-mail and facsimile. RESULTS: The overall response rate was
      79.7%, with 94 of 118 programs responding. Items ranking as most important (4.0
      5.0) in the selection process included: EM rotation grade (mean +/- SD = 4.79 +/-
      0.50), interview (4.62 +/- 0.63), clinical grades (4.36 +/- 0.70), and
      recommendations (4.11 +/- 0.85). Moderate emphasis (3.0-4.0) was placed on:
      elective done at program director's institution (3.75 +/- 1.25), U.S. Medical
      Licensing Examination (USMLE) step II (3.34 +/- 0.93), interest expressed in
      program director's institution (3.30 +/- 1.19), USMLE step I (3.28 +/- 0.86), and
      awards/achievements (3.16 +/- 0.88). Less emphasis (<3.0) was placed on Alpha
      Omega Alpha Honor Society (AOA) status (3.01 +/- 1.09), medical school attended
      (3.00 +/- 0.85), extracurricular activities (2.99 +/- 0.87), basic science grades
      (2.88 +/- 0.93), publications (2.87 +/- 0.99), and personal statement (2.75 +/-
      0.96). Items most agreed upon by respondents (lowest standard deviation, SD)
      included EM rotation grade (SD 0.50), interview (SD 0.63), and clinical grades
      (SD 0.70). Of the 94 respondents, 37 (39.4%) replied they had minimum
      requirements for USMLE step I (195.11 +/- 13.10), while 30 (31.9%) replied they
      had minimum requirements for USMLE step II (194.27 +/- 14.96). Open-ended
      responses to "other" were related to personal characteristics, career/goals, and
      medical school performance. CONCLUSIONS: The selection criteria with the highest
      mean values as reported by the program directors were EM rotation grade,
      interview, clinical grades, and recommendations. Criteria showing the most
      consistency (lowest SD) included EM rotation grade, interview, and clinical
      grades. Results are compared with those from previous multispecialty studies.

PMID- 10894244
TI  - A survey of nonphysician medical screening examinations in academic emergency
      medicine.
AB  - OBJECTIVES: To determine the proportions of U.S. emergency medicine (EM)
      residency programs that use nonphysicians to perform medical screening
      examinations (MSEs) in lieu of a physician evaluation. METHODS: This was a cross
      sectional observational study consisting of a mail survey of the 109 base
      hospitals of accredited U.S. EM residency programs. Follow-up letters were sent
      twice to nonrespondents. Questions regarding ED demographics, the performance and
      structure of MSEs by physicians and nonphysicians, and the exact nature and
      purpose of such examinations were included. RESULTS: Ninety of 109 (83%) programs
      responded. Eighty-seven of the 90 programs (97%) perform MSEs on all patients
      presenting to the ED prior to discharge. Thirty-seven percent (33/90) perform
      nonphysician MSEs (NPMSEs) at least some of the time. Fifty percent (16/32) refer
      patients to an outside facility based on the result of the screening, and in 32%
      of cases the patient is not offered the choice of an ED evaluation. Seventy
      percent (19/27) at times refer patients, including uninsured patients, to a same
      day clinic within their hospital system. Seven of 27 (26%) programs performing
      NPMSEs reported occasional adverse events, defined as two to 11 per year. Eight
      of 22 (36%) reported poorer clinical outcomes than expected from ED care as a
      result of the NPMSE, and 18 of 25 (72%) reported some degree of patient
      dissatisfaction. Two programs reported death as a result of NPMSEs. CONCLUSIONS:
      The use of NPMSEs is common and is frequently used as a basis for referring
      patients away from the ED without a physician examination. Using NPMSEs may be
      associated with adverse events, including patient dissatisfaction, morbidity, and
      possibly, mortality.

PMID- 10894245
TI  - Happy anniversary, ABEM! American Board of Emergency Medicine.

PMID- 10894246
TI  - Screening and brief intervention for alcohol and other drug problems: what will
      it take?

PMID- 10894247
TI  - Can resident physicians be profiled?

PMID- 10894248
TI  - On the future of reanimatology.
AB  - This article is adapted from a presentation given at the 1999 SAEM annual meeting
      by Dr. Peter Safar. Dr. Safar has been involved in resuscitation research for 44
      years, and is a distinguished professor and past initiating chairman of the
      Department of Anesthesiology and Critical Care Medicine at the University of
      Pittsburgh. He is the founder and director of the Safar Center for Resuscitation
      Research at the University of Pittsburgh, and has been the research mentor of
      many critical care and emergency medicine research fellows. Here he presents a
      brief history of past accomplishments, recent findings, and future potentials for
      resuscitation research. Additional advances in resuscitation, from acute terminal
      states and clinical death, will build upon the lessons learned from the history
      of reanimatology, including optimal delivery by emergency medical services of
      already documented cardiopulmonary cerebral resuscitation, basic-advanced
      prolonged life support, and future scientific breakthroughs. Current
      controversies, such as how to best educate the public in life-supporting first
      aid, how to restore normotensive spontaneous circulation after cardiac arrest,
      how to rapidly induce mild hypothermia for cerebral protection, and how to
      minimize secondary insult after cerebral ischemia, are discussed, and must be
      resolved if advances are to be made. Dr. Safar also summarizes future
      technologies already under preliminary investigation, such as ultra-advanced life
      support for reversing prolonged cardiac arrest, extending the "golden hour" of
      shock tolerance, and suspended animation for delayed resuscitation.

PMID- 10894249
TI  - Emergency medicine resident work productivity in an academic emergency
      department.

PMID- 10894250
TI  - Stroke symptom attribution and time to emergency department arrival: the delay in
      accessing stroke healthcare study.

PMID- 10894251
TI  - Emergency department categorization by SAEM is a bad idea. Society for Academic
      Emergency Medicine.

PMID- 10894252
TI  - Emergency department categorization: concerns.

PMID- 10894253
TI  - Emergency department categorization: a historical perspective.

PMID- 10894254
TI  - In response to "Statistical Models and Occam's Razor".

PMID- 10894255
TI  - The relationship context of contraceptive use at first intercourse.
AB  - CONTEXT: Despite widespread efforts to increase contraceptive use to prevent both
      pregnancy and sexually transmitted diseases among sexually active adolescents,
      most prior work examining adolescent contraceptive use does not explicitly
      recognize that sexual decision-making inherently involves both partners in a
      couple. METHODS: An analytic sample of 1,593 females who first had intercourse
      during adolescence (prior to age 18) was drawn from the 1995 National Survey of
      Family Growth. Logistic regression and multinomial logistic regression techniques
      were used to model the effects of sexual partners' characteristics and
      relationship type on contraceptive use at first intercourse and contraceptive
      method selected at first intercourse. RESULTS: Approximately 31% of respondents
      used no contraceptive method at first intercourse. Roughly half (52%) of
      adolescents who had just met their sexual partner used no method, compared with
      24% of those who were going steady. Whereas 75% of teenagers who practiced
      contraception at first intercourse used a condom, 17% relied on the pill. In
      multivariate models, net of other variables, adolescents who had just met their
      partner had 66% lower odds than those who were going steady of practicing
      contraception at first intercourse. Individual-level factors that influenced
      contraceptive use at first intercourse were age at first intercourse, race or
      ethnicity family type, parents' education, grades in school and receipt of birth
      control education prior to first intercourse. Differences between respondents and
      their partner in age and race or ethnicity mostly were not significantly related
      to method use at first intercourse. One exception was that adolescents who first
      had sex with a man six or more years older had reduced odds of practicing
      contraception. Type of relationship was significantly associated with method
      selection only among adolescents who were just friends with their first partner,
      who had higher odds of using "other" methods rather than the condom. Variables
      associated with pill use rather than condom use were age at first sex, race,
      family type, mother's education and school grades. CONCLUSIONS: Further efforts
      to understand contraceptive choice among adolescents should focus on relationship
      features. Research on the decision-making process surrounding contraceptive use
      may benefit from treating this as a partner decision and not just as a decision
      made by one member of the couple. Further research examining the qualities of the
      relationship may provide important clues for understanding adolescent
      contraceptive choice.

PMID- 10894256
TI  - Reconceptualizing adolescent sexual behavior: beyond did they or didn't they?
AB  - CONTEXT: Adolescent sexual behavior is typically studied as a dichotomy:
      Adolescents have had sex or they have not. Broadening this view would lead to a
      greater understanding of teenagers' sexual behavior. METHODS: Interview data from
      907 high school students in Alabama, New York and Puerto Rico were used to
      examine the relationships between sexual experience and a variety of social,
      psychological and behavioral variables. Four groups of teenagers are compared:
      those who did not anticipate initiating sex in the next year (delayers), those
      who anticipated initiating sex in the next year (anticipators), those who had had
      one sexual partner (singles) and those who had had two or more partners
      (multiples). RESULTS: Compared with delayers, anticipators reported more alcohol
      use and marijuana use; poorer psychological health; riskier peer behaviors; and
      looser ties to family school and church. Similarly, multiples reported more
      alcohol and marijuana use, riskier peer behaviors and looser ties to family and
      school than singles. Risk behaviors, peer behaviors, family variables, and school
      and church involvement showed a linear trend across the four categories of sexual
      behavior. CONCLUSIONS: The traditional sex-no sex dichotomy obscures differences
      among sexually inexperienced teenagers and among adolescents who have had sex.
      Prevention efforts must be tailored to the specific needs of teenagers with
      differing sexual experiences and expectations, and must address the social and
      psychological context in which sexual experiences occur.

PMID- 10894257
TI  - Trends in adolescent males' abortion attitudes, 1988-1995: differences by race
      and ethnicity.
AB  - CONTEXT: Studying how adolescent males view abortion and how their attitudes
      toward abortion have changed over time can improve our understanding of the
      sexual, contraceptive and abortion behavior of these males and their partners.
      METHODS: Data from the 1988 and 1995 National Survey of Adolescent Males are used
      to describe changes in young males' attitudes toward abortion over time, as well
      as differences in abortion attitudes by race and ethnicity. Multivariate models
      are used to examine the relationship between religiosity and abortion attitudes.
      RESULTS: Between 1988 and 1995, young males' approval of abortion decreased
      significantly. In 1995, 24% of U.S. males aged 15-19 agreed that it was all right
      for a woman to have an abortion "for any reason," down from 37% in 1988. This
      decrease was driven almost entirely by non-Hispanic white males; there was little
      change in the abortion attitudes of non-Hispanic blacks and Hispanics. The
      decrease in white males' approval of abortion coincides with a significant
      increase in the self-reported importance of religion and in the proportion of
      whites who identified themselves as born-again Christians. The proportion of non
      Hispanic white males indicating that religion was very important increased from
      28% in 1988 to 34% in 1995, while the proportion identifying themselves as born
      again increased from 18% to 24%. Multivariate analyses indicate that religiosity
      was more strongly related to the abortion attitudes of non-Hispanic whites than
      to those of Hispanics or non-Hispanic blacks. CONCLUSIONS: The large decrease in
      approval of abortion among white teenage males has closed the racial and ethnic
      gap in attitudes toward abortion that was evident in 1988, when such youth held
      significantly more liberal attitudes toward abortion than did either Hispanics or
      blacks. This trend toward more conservative abortion-related attitudes among
      whites coincides with increasingly conservative attitudes regarding premarital
      sex and greater religiosity among white male adolescents.

PMID- 10894258
TI  - Factors affecting contraceptive use in women seeking pregnancy tests: Missouri,
      1997.
AB  - CONTEXT: If the national health objective of reducing unintended pregnancy is to
      be met, a better understanding is needed of barriers to women's acquisition and
      use of contraceptives. METHODS: A sample of 311 Missouri women who were seeking
      pregnancy tests in public health department clinics in 1997 and who said their
      potential pregnancy was unintended were asked about potential barriers to family
      planning. Factors affecting contraceptive use among these women were examined by
      frequency of use, insurance status, education and race. RESULTS: In general, the
      women mostly disagreed that particular factors were potential barriers to
      contraceptive use. For only one item--worry over the potential side effects of
      the hormonal injectable contraceptive--did a majority agree or strongly agree
      that it was a barrier to method use in the previous six months. Women who used a
      contraceptive infrequently were more likely than frequent users to identify 33
      factors in nine areas as being potential barriers to contraceptive use. These
      ranged from factors involving access to services and condom-specific issues to
      cost-related concerns, social norms, pregnancy denial, embarrassment over
      discussing or obtaining birth control, worry about side effects and experience
      with forced sex, among others. Perceived barriers differed somewhat by insurance
      status in the areas of access, embarrassment, side effects and forced sex. For
      example, women with no insurance coverage reported a higher level of agreement
      that transportation problems had hindered their access to a clinic than did women
      with private insurance. Level of education affected agreement only in the area of
      side effects, with more-educated women expressing greater concern about side
      effects than less-educated women. The respondent's race affected agreement in six
      areas: access, social norms, pregnancy denial, embarrassment, forced sex and
      other miscellaneous concerns, such as condom use and relationship issues.
      CONCLUSION: Better education and improved access to and delivery of services
      might address several factors affecting contraceptive use that are associated
      with unintended pregnancy. Some barriers, however, such as those related to self
      efficacy, self-esteem and fatalistic attitudes about pregnancy, would be much
      harder for family planning providers to resolve.

PMID- 10894259
TI  - Use of infertility services in the United States: 1995.
AB  - CONTEXT: Both the demand for and the availability of infertility services in the
      United States increased during the 1980s and early 1990s. Understanding the
      factors that are related to service-seeking among women with current fertility
      problems would aid efforts to better provide services. METHODOLOGY: Data on U.S.
      women's use of infertility services were taken from the 1995 National Survey of
      Family Growth, a nationally representative survey of 10,847 women aged 15-44. For
      the 1,210 women who at the time of the interview reported having fertility
      problems, multivariate statistical modeling was used to identify the
      characteristics associated with their use of infertility services. RESULTS: Of
      the 6.7 million women with fertility problems in 1995, 42% had received some form
      of infertility services. The most common services ever received among these women
      were advice (60%) and diagnostic tests (50%), medical help to prevent miscarriage
      (44%) and drugs to induce ovulation (35%). The proportions of fertility-impaired
      women who had ever received infertility services were generally highest among
      those who were older, who had ever been married, who had graduated from college,
      who had a high income and who were non-Hispanic white. Multivariate analyses
      reveal that apparent differences by age and race or ethnicity in the unadjusted
      analysis disappear once the effects of women's marital status, income and private
      health insurance coverage are taken into account. CONCLUSION: Women who have ever
      used infertility services continue to represent a select group from among those
      with impaired fertility. Moreover, the vast majority of women with fertility
      problems who seek services receive noninvasive treatments that could be
      considered "low technology" interventions.

PMID- 10894260
TI  - Female condom use among women at high risk of sexually transmitted disease.
AB  - CONTEXT: Whereas the female condom has been evaluated in many hypothetical
      acceptability or short-term use studies, there is little information about its
      suitability for the prevention of sexually transmitted diseases (STDs) or HIV
      over extended periods of time. METHODOLOGY: As part of a six-month prospective
      follow-up study of 1,159 STD clinic patients, clients were interviewed during
      their initial visit, exposed to a behavioral intervention promoting condoms,
      given a physical examination and provided with instructions on completing a
      sexual diary. Potential predictors of trying the female condom were evaluated
      using logistic regression, and three condom-use groups (exclusive users of female
      condoms, exclusive users of male condoms and users of both types of condoms) were
      compared using multinomial regression. RESULTS: Among 895 women who reported
      having engaged in vaginal intercourse during the study period, one-half had sex
      with only one partner, while one-quarter each had two partners or three or more
      partners. A total of 731 women reported using the female condom at least once
      during the follow-up period--85% during the first month of follow-up. Multiple
      logistic regression analyses indicated that employed women and those with a
      regular sexual partner at baseline were significantly more likely to try the
      female condom. By the end of the follow-up period, 8% of participants had used
      the female condom exclusively, 15% had used the male condom exclusively, 73% had
      used both types of condom and 3% had used no condoms. Twenty percent of women who
      tried the female condom used it only once and 13% used it twice, while 20% used 5
      9 female condoms and 32% used 10 or more. Consistent condom users (N=309) were
      predominantly users of both types of condom (75%), and were less often exclusive
      users of the male condom (18%) or the female condom (7%). According to a
      multivariate analysis, women who used the female condom exclusively or who mixed
      condom types were more likely to be black, were more likely to be employed and
      were more likely to have a regular partner than were users of the male condom.
      CONCLUSIONS: Women at risk of STDs find the female condom acceptable and will try
      it, and some use it consistently. Mixing use of female condoms and male condoms
      may facilitate consistent condom use. The female condom may improve an
      individual's options for risk reduction and help reduce the spread of STDs.

PMID- 10894261
TI  - Prodrug activation enzymes in cancer gene therapy.
AB  - Among the broad array of genes that have been evaluated for tumor therapy, those
      encoding prodrug activation enzymes are especially appealing as they directly
      complement ongoing clinical chemotherapeutic regimes. These enzymes can activate
      prodrugs that have low inherent toxicity using both bacterial and yeast enzymes,
      or enhance prodrug activation by mammalian enzymes. The general advantage of the
      former is the large therapeutic index that can be achieved, and of the latter,
      the non-immunogenicity (supporting longer periods of prodrug activation) and the
      fact that the prodrugs will continue to have some efficacy after transgene
      expression is extinguished. This review article describes 13 different prodrug
      activation schemes developed over the last 15 years, two of which - activation of
      ganciclovir by viral thymidine kinase and activation of 5-fluorocytosine to 5
      fluorouracil - are currently being evaluated in clinical trials. Essentially all
      of these prodrug activation enzymes mediate toxicity through disruption of DNA
      replication, which occurs at differentially high rates in tumor cells compared
      with most normal cells. In cancer gene therapy, vectors target delivery of
      therapeutic genes to tumor cells, in contrast to the use of antibodies in
      antibody-directed prodrug therapy. Vector targeting is usually effected by direct
      injection into the tumor mass or surrounding tissues, but the efficiency of gene
      delivery is usually low. Thus it is important that the activated drug is able to
      act on non-transduced tumor cells. This bystander effect may require cell-to-cell
      contact or be mediated by facilitated diffusion or extracellular activation to
      target neighboring tumor cells. Effects at distant sites are believed to be
      mediated by the immune system, which can be mobilized to recognize tumor antigens
      by prodrug-activated gene therapy. Prodrug activation schemes can be combined
      with each other and with other treatments, such as radiation, in a synergistic
      manner. Use of prodrug wafers for intratumoral drug activation and selective
      permeabilization of the tumor vasculature to prodrugs and vectors should further
      increase the value of this new therapeutic modality.

PMID- 10894262
TI  - Knock-out mouse for Canavan disease: a model for gene transfer to the central
      nervous system.
AB  - BACKGROUND: Canavan disease (CD) is an autosomal recessive leukodystrophy
      characterized by deficiency of aspartoacylase (ASPA) and increased levels of N
      acetylaspartic acid (NAA) in brain and body fluids, severe mental retardation and
      early death. Gene therapy has been attempted in a number of children with CD. The
      lack of an animal model has been a limiting factor in developing vectors for the
      treatment of CD. This paper reports the successful creation of a knock-out mouse
      for Canavan disease that can be used for gene transfer. METHODS: Genomic library
      lambda knock-out shuttle (lambdaKOS) was screened and a specific pKOS/Aspa clone
      was isolated and used to create a plasmid with 10 base pair (bp) deletion of exon
      four of the murine aspa. Following linearization, the plasmid was electroporated
      to ES cells. Correctly targeted ES clones were identified following positive and
      negative selection and confirmed by Southern analysis. Chimeras were generated by
      injection of ES cells to blastocysts. Germ line transmission was achieved by the
      birth of heterozygous mice as confirmed by Southern analysis. RESULTS:
      Heterozygous mice born following these experiments have no overt phenotype. The
      homozygous mice display neurological impairment, macrocephaly, generalized white
      matter disease, deficient ASPA activity and high levels of NAA in urine. Magnetic
      resonance imaging (MRI) and spectroscopy (MRS) of the brain of the homozygous
      mice show white matter changes characteristic of Canavan disease and elevated NAA
      levels. CONCLUSION: The newly created ASPA deficient mouse establishes an
      important animal model of Canavan disease. This model should be useful for
      developing gene transfer vectors to treat Canavan disease. Vectors for the
      central nervous system (CNS) and modulation of NAA levels in the brain should
      further add to the understanding of the pathophysiology of Canavan disease. Data
      generated from this animal model will be useful for developing strategies for
      gene therapy in other neurodegenerative diseases.

PMID- 10894263
TI  - Novel bovine lentiviral vectors based on Jembrana disease virus.
AB  - BACKGROUND: Safety is a concern that must be addressed prior to any clinical use
      of human immunodeficiency virus (HIV)-based lentiviral vectors in human patients.
      Unfortunately, efforts to examine the biosafety of the vectors in preclinical
      animal models are hampered due to the lack of animal models for HIV infection. We
      have developed new lentiviral vectors based on the recently characterised
      Jembrana Disease Virus (JDV), which infects a specific species of cattle
      naturally in Bali, Indonesia. METHODS: Sequences from the JDV genome were
      amplified by splicing overlap extension polymerase chain reaction (PCR) for the
      construction of transfer vectors as well as a packaging construct. Co
      transfection of these two plasmids into 293T cells with a third encoding a G
      glycoprotein of vesicular stomatitis virus produced pseudotyped, disabled,
      replication defective JDV vector particles. Viral titre was obtained by
      transducing the cells with the supernatant harvested from transfectants and
      determining the number of cells expressing the transgene. PCR and Southern
      blotting were used to detect the presence of potential replication-competent
      viruses as well as transgene integration. RESULTS: Bicistronic JDV vectors
      encoding the green fluorescent protein (GFP) and the neomycin phosphotransferase
      were harvested with a titre range of 0.4-1.2 x 10(6) colony forming units/ml from
      vector-producing cells and were further concentrated by ultracentrifugation to
      the high titre of approximately 10(7) CFU/ml. Vectors encoding GFP were shown to
      transduce and integrate efficiently into the chromosomes of a range of primary
      and transformed cells of different origins in different differentiation status,
      including growth-arrested cells, with an efficiency of 25-75%. Exhaustive testing
      with a marker gene transfer assay in combination with a reverse transcriptase
      assay and PCR amplification of samples of serially passaged, transduced cells
      showed that no detectable amount of replication competent lentivirus (RCL) was
      produced. CONCLUSIONS: We showed the feasibility of the development of gene
      transfer vectors based on a non-primate bovine lentivirus, which will provide the
      opportunity for examination of the efficacy and biosafety of lentiviral vector
      mediated gene transfer in vivo in animal models. JDV-based vectors may be
      applicable and more readily acceptable than those from HIV for human gene
      therapy.

PMID- 10894264
TI  - The application of a lentiviral vector for gene transfer in fetal human
      hepatocytes.
AB  - BACKGROUND: The applications of traditional retroviral vectors are limited
      because proviral integrations into the host genome require DNA synthesis.
      Lentiviruses are considered to be advantageous because of their ability to infect
      non-dividing cells. METHODS: To demonstrate the potential of lentiviral vectors,
      we used a human immunodeficiency virus (HIV)-1 virus encoding the green
      fluorescence protein (GFP) to infect fetal human hepatocytes. GFP-expressing
      cells were transplanted into the liver of Balb/C SCID mice via intrasplenic
      injection. RESULTS: Primary fetal hepatocytes incorporated the GFP reporter with
      high (30-40%) efficiency. A cell line derived from human fetal liver (HFL)
      exhibited similar transduction efficiency to the lentiviral vector. To
      demonstrate the relationship between lentiviral gene transfer and cell
      proliferation, cells were subjected to gamma-irradiation, which attenuated the
      replication of primary fetal hepatocytes. However, lentiviral gene transfer was
      unaffected by this decrease in cell proliferation. GFP expression in transduced
      cells was preserved during multiple passages in cell culture. When GFP-expressing
      cells were transplanted into the liver of Balb/C SCID mice via intrasplenic
      injection, GFP expression was observed throughout the 3 week duration of the
      study. CONCLUSION: These studies establish that human hepatocytes are amenable to
      lentiviral gene transfer with sustained transgene expression. Incorporation of
      lentiviral vectors will be helpful in testing strategies for hepatic gene
      therapy.

PMID- 10894265
TI  - The role of IL-6 in the inflammatory and humoral response to adenoviral vectors.
AB  - BACKGROUND: The major concern for the use of adenoviral vectors for gene therapy
      is the viral-induced immune response that has been shown to be responsible for
      short-term transgene expression and inefficient viral readministration. In vivo
      studies and clinical trials with recombinant adenovirus have suggested a role for
      interleukin 6 (IL-6) in the inflammatory reaction that follows Ad-infection. IL-6
      plays an important role in the acute-phase innate response, in the
      differentiation of B-cells and in the activation of the Th2 cell subsets.
      METHODS: To clarify the role of IL-6 in the immune response to Ad-vectors, we
      used IL-6 knock-out mice (IL-6 -/- ). E1/E3 deleted recombinant adenoviruses
      encoding reporter genes were administered to wild type or IL-6-/- mice; transgene
      expression kinetics and immune response were analyzed. RESULTS: Acute phase
      protein production was significantly diminished in IL-6 -/- mice after adenoviral
      injection. No significant difference between wild type and knock-out animals in
      the level or the nature of leucocyte recruitment in the liver was detectable. A
      minor decrease in the IgG response to Ad-recombinants was observed in knock-out
      mice. Gene transfer efficiency, both in terms of levels and duration of transgene
      expression, were comparable in IL-6+/+ and IL-6-/- mice. An increase in IL-1beta
      and tumor necrosis factor-alpha (TNF-alpha) levels was observed in the sera of IL
      6 -/- mice as compared to wild type animals: this phenomenon represents a
      possible compensatory mechanism for the establishment of the immune phenotype
      observed in mutant mice. CONCLUSIONS: IL-6 plays a role in the acute phase
      response to adenoviral vectors. Nevertheless, possibly due to a compensatory
      mechanism exerted by other cytokines, the antibody and cellular responses to
      adenoviruses are very similar in wild type and IL-6 -/- mice.

PMID- 10894266
TI  - BTK mediated apoptosis, a possible mechanism for failure to generate high titer
      retroviral producer clones.
AB  - BACKGROUND: It has been shown previously that mutations in the cytoplasmic
      protein kinase, Bruton's tyrosine kinase (BTK) lead to X-linked
      agammaglobulinemia, an inherited primary immunodeficiency, thus making it a
      potential candidate for gene therapy. METHODS: Producer cell lines using
      retroviral BTK constructs were generated and retroviral titers determined.
      Southern blot analysis was performed to check for pro-viral integrity in the
      respective clones. Furthermore, cotransfection of green fluorescent protein (GFP)
      with BTK expression plasmids was used in HeLa cells to establish and characterize
      the role of BTK in apoptosis. RESULTS: Following the attempt to generate
      retroviral producer clones by conventional methods, we observed that the BTK gene
      is deleted from neomycin-resistant high titer clones. We show that BTK mediated
      apoptosis in GP#E86 and HeLa cells. Furthermore, membrane targeting and kinase
      activity are required for this effect. In addition, BTK induced apoptosis could
      be inhibited by using a specific inhibitor for p38 mitogen-activated protein
      kinase (MAPK), SB203580. CONCLUSION: Failure to generate retroviral producer
      clones may be caused by the induction of apoptosis mediated by the therapeutic
      gene product.

PMID- 10894267
TI  - Adenoviral mediated delivery of FAS ligand to arthritic joints causes extensive
      apoptosis in the synovial lining.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease where the synovial
      lining layer of the joint becomes thickened, hypercellular, and highly
      aggressive. Invading synovial tissue erodes cartilage and subchondral bone and
      leads to loss of joint function. FasL, a cell-surface molecule on activated T
      cells interacts with its receptor, Fas, to induce apoptosis in target cells. We
      addressed the feasibility of using adenoviral gene transfer of FasL
      therapeutically to mediate apoptosis in arthritic joints similar in size to the
      small joints of the hands and feet that are the primary sites of RA in humans.
      METHODS: Adenoviral vectors were used to transfer FasL and LacZ cDNAs into human
      RA and rabbit synovial fibroblasts in culture where apoptosis was evaluated using
      MTT and TUNEL analyses. The ability of Ad.FasL to mediate synovial apoptosis in
      vivo was then addressed in an IL-1-induced arthritis model in the rabbit knee.
      RESULTS: In culture, delivery of FasL was found to efficiently induce apoptosis
      in both human RA and rabbit synovial fibroblasts. The ability of Ad.FasL to
      induce synovial apoptosis was then evaluated in rabbit knee joints. 24 h after
      intra-articular injection of 10(11) Ad.FasL particles, large regions of synovial
      tissue were observed histologically consisting primarily of fibrous matrix and
      cellular debris. TUNEL staining of corresponding sections was highly positive for
      fragmented DNA. Glycosaminoglycan (GAG) synthesis from cartilage shavings from
      treated joints suggests that Ad.FasL does not induce significant apoptosis in
      resident articular chondrocytes. CONCLUSIONS: Infection of human and rabbit
      synovial fibroblasts with Ad.FasL results in significant apoptotic cell death in
      vitro. Direct intra-articular injection of Ad.FasL in the arthritic rabbit knee
      results in extensive apoptosis in the synovium without affecting chondrocyte
      viability.

PMID- 10894268
TI  - A randomized study of antiretroviral management based on plasma genotypic
      antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study
      Team for the Terry Beirn Community Programs for Clinical Research on AIDS.
AB  - OBJECTIVE: To determine the short-term effects of using genotypic antiretroviral
      resistance testing (GART) with expert advice in the management of patients
      failing on a protease inhibitor and two nucleoside reverse transcriptase
      inhibitors. DESIGN: Prospective randomized controlled trial. SETTING: Multicenter
      community-based clinical trials network. PATIENTS: One-hundred and fifty-three
      HIV-infected adults with a threefold or greater rise in plasma HIV-1 RNA on at
      least 16 weeks of combination antiretroviral therapy. INTERVENTIONS:
      Randomization was either to a GART group, where genotype interpretation and
      suggested regimens were provided to clinicians, or to a no-GART group, where
      treatment choices were made without such input. MAIN OUTCOMES MEASURES: Plasma
      HIV-1 RNA levels and CD4 cell counts were measured at 4, 8, and 12 weeks
      following randomization. The primary endpoint was change in HIV-1 RNA levels from
      baseline to the average of the 4 and 8 week levels. RESULTS: The average baseline
      CD4 cell count was 230 x 10(6) cells/l and the median HIV-1 RNA was 28,085
      copies/ml. At entry, 82 patients were failing on regimens containing indinavir,
      51 on nelfinavir, 11 on ritonavir, and nine on saquinavir. HIV-1 RNA, averaged at
      4 and 8 weeks, decreased by 1.19 log10 for the 78 GART patients and -0.61 log10
      for the 75 no-GART patients (treatment difference: -0.53 log, 95% confidence
      interval, -0.77 to -0.29; P = 0.00001). Overall, the best virologic responses
      occurred in patients who received three or more drugs to which their HIV-1
      appeared to be susceptible. CONCLUSION: In patients failing triple drug therapy,
      GART with expert advice was superior to no-GART as measured by short-term viral
      load responses.

PMID- 10894269
TI  - Phenotypic testing predicts virological response in successive protease inhibitor
      based regimens.
AB  - OBJECTIVE: To evaluate the importance of the number of active drugs, as
      determined by phenotypic resistance testing, in achieving virological response in
      successive salvage regimens. DESIGN: Phenotypic study of 57 plasma samples
      corresponding to 24 patients who had sequentially received three protease
      inhibitor-containing regimens. Phenotypic susceptibility to a drug (active drug)
      was defined as less than a four-fold-increase in the IC50 in comparison with the
      wild type. MAIN OUTCOME MEASURE: Virological response according to the number of
      active drugs (three versus two or fewer), HIV load, length of antiretroviral
      exposure, and line of protease inhibitor-based therapy (first, second and third
      regimen). RESULTS: Before the first protease inhibitor-based therapy, the median
      time on antiretroviral treatment was 42 months, and before the second and third
      protease inhibitor-salvage regimens it was 10 and 8 months, respectively. The
      number of patients receiving three active drugs simultaneously was 24, 35 and 31%
      in each line of therapy. At week 12, a close correlation was found between the
      presence of three active drugs in the antiretroviral regimen and the rate of
      virological response, in comparison with those patients receiving two or fewer
      active drugs [76 versus 45%, relative risk (RR), 1.7; 95% confidence interval
      (CI) 1.1-2.6; P = 0.028]. In a multivariate analysis, the use of two or fewer
      active drugs was an independent predictor of lack of response, regardless of HIV
      load, length of previous antiretroviral exposure and line of salvage therapy (RR,
      4.5; 95%CI, 1.1-18.3; P = 0.03). Of note, a higher rate of response was observed
      in patients receiving the first protease inhibitor-containing regimen in
      comparison with those in subsequent protease inhibitor-based salvage regimens (83
      versus 50 versus 28%, P < 0.01), even when only those patients receiving three
      active drugs were included (100 versus 71 versus 60%). CONCLUSIONS: This data
      confirm the usefulness of phenotypic testing in guiding antiretroviral therapy in
      heavily pretreated patients. The number of active drugs and the line of salvage
      therapy are independent predictors of virological response, regardless of HIV
      load and the length of antiretroviral exposure.

PMID- 10894270
TI  - Once-daily dosing of saquinavir and low-dose ritonavir in HIV-1-infected
      individuals: a pharmacokinetic pilot study.
AB  - OBJECTIVE: To investigate the steady-state pharmacokinetics of a once-daily
      dosing regimen of saquinavir soft gelatin capsules in combination with a low dose
      of ritonavir in HIV-1-infected individuals. DESIGN: Open-label, multi-dose,
      pharmacokinetic pilot study. PATIENTS: Seven HIV-1-infected individuals who were
      treated with saquinavir hard gelatin capsules 400 mg twice daily + ritonavir
      liquid formulation 400 mg twice daily were switched to saquinavir soft gelatin
      formulation 1600 mg once daily in combination with ritonavir liquid formulation
      200 mg once daily (day 0). Patients were instructed to ingest saquinavir and
      ritonavir simultaneously in the morning and with a meal. METHODS: Steady-state
      pharmacokinetics of saquinavir and ritonavir were assessed during a 24 h dosing
      interval after 2 weeks of continued therapy (day 14). Plasma saquinavir and
      ritonavir concentrations were measured using a validated high performance liquid
      chromatography assay. In addition, plasma HIV-1 RNA, and fasting total
      cholesterol, high-density lipoprotein, low-density lipoprotein, and triglyceride
      levels were measured on days 0 and 14. A non-compartmental pharmacokinetic method
      was used to calculate the area under the plasma concentration versus time curve
      (AUC[0-24h]), the maximum and trough plasma concentrations (Cmax and Cmin), the
      time to reach Cmax (Tmax), the elimination half-life (t1/2), the apparent
      clearance (Cl/F), and the apparent volume of distribution (V/F). RESULTS: Median
      (range) values of the pharmacokinetic parameters for saquinavir after 2 weeks of
      treatment were: AUC[0-24h], 19,802h* ng/ml (3720-74,016); Cmax, 2936 ng/ml (573
      6848); Cmin, 84 ng/ml (11-854); Tmax, 3.5 h (3.0-4.0), t1/2, 6.8 h (4.6-10.2);
      Cl/F, 81 l/h (22-430); V/F, 1189 l (215-3086). Ritonavir concentrations were
      always below the 90% effective concentration of 2100 ng/ml (median Cmax, 1323
      ng/ml; range, 692-1528 ng/ml). No significant changes were observed for total
      serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels
      between days 0 and 14 (P > or = 0.24). In six out of seven patients the fasting
      serum triglyceride levels were lower 2 weeks after the treatment switch (median
      decrease was 32%, P = 0.03). No significant changes in plasma HIV-1 RNA
      concentrations were observed between days 0 and 14. The regimen was generally
      well tolerated. CONCLUSIONS: This pharmacokinetic study indicates that the
      combination of 1600 mg of saquinavir (soft gelatin capsules) and 200 mg of
      ritonavir (liquid formulation) in a once-daily dosing regimen generally results
      in therapeutic plasma concentrations of saquinavir. Due to the large
      interindividual variation in saquinavir exposure, the monitoring of saquinavir
      concentrations in plasma is warranted. These pharmacokinetic findings rationalize
      the further clinical evaluation of once-daily dosing of this combination of
      protease inhibitors.

PMID- 10894271
TI  - Role of CD38 in HIV-1 infection: an epiphenomenon of T-cell activation or an
      active player in virus/host interactions?

PMID- 10894272
TI  - Prevention of infectious complications of paediatric HIV infection in Africa.

PMID- 10894273
TI  - Quantitative evaluation of the recombinant HIV-1 phenotype to protease inhibitors
      by a single-step strategy.
AB  - OBJECTIVE: To develop and optimize a fast and quantitative recombinant strategy
      for evaluating the HIV-1 phenotype to protease inhibitors (PI). DESIGN AND
      METHODS: A non-replicative HIV-1 molecular vector (designated pdelta prodelta
      env) capable of expressing exogenous HIV-1 protease-encoding sequences was
      developed in this study. The HIV-1 protease sequences were amplified from either
      viral isolates or plasma samples (both from 21 HIV-1-infected individuals, 19 of
      whom were failing different anti-HIV-1 combination treatments) and cloned in the
      pdelta prodelta env backbone. The HIV-1 recombinant phenotype to PI was
      determined directly after transfection of viral chimeric clones by measuring
      protease activity and calculating a percentage sensitivity index (SI%; the ratio
      between the results from each clone and those from a PI-sensitive reference
      strain). RESULTS: The SI% values obtained from the recombinant clones paralleled
      the IC50 results of the viral isolates and documented different degrees of
      resistance and cross-resistance to PI, compatible, with few exceptions, with the
      respective genotype. Interestingly, an inverse correlation between SI% values and
      the presence of primary mutations for resistance to PI (P = 0.0038 and P =
      0.0414, for indinavir and ritonavir, respectively) and a difference in SI%
      between samples harbouring an increasing number of mutations (indinavir, P =
      0.022; ritonavir, P = 0.0466) were observed. CONCLUSION: The data substantiate
      the reliability of the novel strategy for a fast (5 day) quantitative evaluation
      of HIV-1 phenotype to PI, and indicate that this method may contribute to the
      understanding of mechanisms of virus resistance to PI.

PMID- 10894274
TI  - Evolution of lamivudine-resistant hepatitis B virus and HIV-1 in co-infected
      individuals: an analysis of the CAESAR study. CAESAR co-ordinating committee.
AB  - OBJECTIVES: Lamivudine has potent activity against HIV-1 and hepatitis B virus
      (HBV). Co-infection with these two viruses is common, and this may therefore
      influence the choice of antiretroviral therapies. A cohort of co-infected
      patients treated with lamivudine were studied in order to evaluate the
      differential effects of lamivudine on the two viral populations within the same
      individual after 44-52 weeks of therapy. DESIGN AND METHODS: Retrospective
      virological analysis of an HIV-1/HBV co-infected lamivudine cohort derived from a
      randomized, placebo-controlled study of lamivudine in HIV infection, the CAESAR
      study. RESULTS: Five of thirteen patients with HBV viral load > 10,000 copies/ml
      after 44-52 weeks of lamivudine therapy had genotypic drug resistance. Four of
      these five had a rebound of viral replication over the period of study and in one
      case this was associated with an alanine transaminase serum elevation. Ten of the
      thirteen patients had a 44-52 week HIV viral load > 1000 copies/ml, all of whom
      also had HIV reverse transcriptase M184V or M184I mutations. CONCLUSIONS:
      Extrapolating these results to the population yields an estimated 1-year
      incidence of drug-resistant HBV of at least 14% in lamivudine-treated HIV-1/HBV
      co-infected patients. The clinical and virological benefit of HBV lamivudine
      monotherapy in co-infected patients should be balanced against the potential for
      emergence of drug resistance. Further, these data suggest that the determinants
      of HIV and HBV drug resistance are different and that parallel evolution, rather
      than co-evolution of HBV and HIV-1 in co-infected individuals occurs.

PMID- 10894275
TI  - Absence of specific mucosal antibody responses in HIV-exposed uninfected sex
      workers from the Gambia.
AB  - OBJECTIVES: Specific antibodies to HIV envelope that inactivate virus at the
      mucosal surfaces involved in sexual contact are of interest for the design of a
      vaccine against HIV-1. It has been suggested that, in frequently HIV-exposed but
      uninfected individuals, HIV-specific mucosal antibody responses may exist and
      play a role in resistance against HIV. This study investigated HIV-1 envelope
      specific mucosal antibody responses in HIV-resistant sex workers in west Africa.
      METHODS: A group of 26 exposed uninfected female commercial sex workers from the
      Gambia, who have had repeated exposures to HIV-1 and HIV-2 were studied. We
      assessed the presence of vaginal IgA and IgG in vaginal swabs against a range of
      HIV-1 and HIV-2 envelope presentations and performed HIV-1 neutralization assays.
      RESULTS: No significant vaginal IgA or IgG responses against HIV-1 or HIV-2 were
      detected, and none of the vaginal secretions tested displayed any HIV-1
      neutralizing activity. CONCLUSION: Vaginal antibody responses against HIV were
      not found in Gambian sex workers who resist HIV infection. Resistance against HIV
      infection can therefore occur in the absence of specific antibodies against HIV
      at the genital mucosa. A protective role for HIV-envelope specific IgA in
      resistance against HIV-1 infection in exposed uninfected individuals as reported
      in the literature is uncertain.

PMID- 10894276
TI  - The restricted cellular host range of human herpesvirus 8.
AB  - DESIGN: A selection of primary and transformed cell types were evaluated for
      their susceptibility to infection with human herpesvirus 8 (HHV-8)/Kaposi's
      sarcoma-associated herpesvirus. METHODS: Sources of HHV-8 included Kaposi's
      sarcoma lesion punch biopsies that were either cocultured directly with target
      cells or that were first cocultured with human lymphocytes to derive HHV-8
      containing fluids that were inoculated onto target cells. HHV-8 was also obtained
      from primary effusion lymphoma-derived cell lines. Techniques to detect infection
      included the PCR, immunofluorescence assays and in situ hybridization. RESULTS:
      Susceptible cells included human umbilical cord blood mononuclear cells (UCMC),
      adult CD19 B cells, macrophages and certain endothelial cells of human and animal
      origin, including some that are transformed with human papilloma virus type 16 E6
      and E7 genes. The infection of lymphocytes did not yield established
      lymphoblastoid cell lines (LCL) and virus infection persisted for only 4-7 days.
      However, long-term HHV-8 infection of UCMC could be achieved by coinfection with
      Epstein-Barr virus. HHV-8 could also infect UCMC LCL recently derived by Epstein
      Barr virus transformation, but long-established LCL could not be infected with
      HHV-8. CONCLUSIONS: These data provide further biological evidence in cell
      culture for the limited cellular host range of HHV-8 to CD19 B cells,
      macrophages, and certain endothelial cells.

PMID- 10894277
TI  - Effect of clinical events on plasma HIV-1 RNA levels in persons with CD4+ T
      lymphocyte counts of more than 500 x 10(6) cells/l.
AB  - OBJECTIVE: Immune stimulation of CD4 lymphocytes is thought to enhance HIV-1
      replication in vivo. Therefore, we sought to define the impact of clinical events
      identified as putative immune activators on the variability of plasma HIV-1 RNA
      levels in persons with CD4 cell counts greater than 500 x 10(6) cells/l. DESIGN:
      We prospectively recorded clinical events and measured plasma HIV-1 RNA levels
      weekly for 24 weeks in 16 HIV-1-infected adults who were not receiving
      antiretroviral therapy and who had CD4 cell counts greater than 500 x 10(6)
      cells/l. METHODS: Standard weekly interviews were conducted to capture potential
      immune activators (e.g., infections, immunizations, and allergic reactions). All
      plasma HIV-1 RNA levels were measured using the Amplicor HIV-1 Monitor assay
      (Roche Diagnostics, Branchburg, New Jersey, USA) according to the manufacturer's
      instructions. RESULTS: Participants had remarkably stable viral loads during the
      6 month study period. Infections were significantly more frequent during the 7
      days prior to individual HIV-1 RNA measurements that exceeded the assay variation
      thresholds determined for this study (+/- 0.324 log) than during the comparable
      time periods preceding stable measurements (P = 0.023). As a group, the eight
      participants who had one to four HIV-1 RNA measurements that exceeded the
      thresholds experienced more infections and declining CD4 cell counts over the
      study course compared to the eight participants whose measurements all fell
      within the thresholds (P = 0.058 and 0.053 respectively). CONCLUSIONS: Our study
      suggests that in untreated HIV-1-infected persons with CD4 cell count greater
      than 500 x 10(6) cells/l, viral load is generally quite stable, although acute
      minor infections are associated with transient fluctuations generally lasting no
      more than 1 week.

PMID- 10894278
TI  - The values of quantitative serum HIV-1 RNA levels and CD4 cell counts for
      predicting survival time among HIV-positive individuals with CD4 counts of < or =
      50 x 10(6) cells/l.
AB  - OBJECTIVE: To evaluate the HIV-1 RNA level as a predictor of survival time among
      individuals with advanced AIDS. METHODS: The serum HIV-1 RNA level, the CD4 cell
      count, and other clinical variables were evaluated at baseline, as predictors of
      survival time, among 56 retrospectively identified HIV-1 positive individuals
      with < or = 50 x 10(6) CD4 cells/l who attended the Beth Israel Deaconess Medical
      Center, Division of Infectious Diseases, between 1 July 1989 and 30 September
      1993. RESULTS: During follow-up, 55 of these 56 patients died. The median
      survival time was 20.5 months. In univariate Cox proportional hazard modeling
      neither the baseline HIV-1 RNA level nor the CD4 cell count were predictive of
      survival time. However, in multivariate models longer survival time was
      associated with the use of trimethoprim-sulphamethoxazole at entry [hazard ratio
      (HR), 0.42; P = 0.007], whereas shorter survival time was associated with a
      history of an AIDS-defining illness other than Pneumocystis carinii pneumonia
      (HR, 2.87; P = 0.007). Correlative analysis revealed a modest correlation of the
      baseline CD4 cell count with survival time (Spearman p = 0.41; P = 0.002).
      However, no correlation was found between HIV RNA levels and survival time (P =
      0.5). CONCLUSIONS: In this population with very advanced disease, the HIV-1 RNA
      level was a poor discriminator of survival time, being inferior to the CD4 cell
      count and to specific clinical variables such as the nature of the prior AIDS
      defining illness and the type of Pneumocystis carinii pneumonia prophylaxis
      employed. Among individuals with advanced AIDS, these data emphasize the relative
      importance of the CD4 cell count and of specific clinical factors, over the HIV-1
      RNA level in predicting survival time.

PMID- 10894279
TI  - Strong association between failure of T cell homeostasis and the syncytium
      inducing phenotype among HIV-1-infected men in the Amsterdam Cohort Study.
AB  - OBJECTIVE: To assess the association between T cell homeostasis and its failure
      and 1.) the occurrence of AIDS and 2.) the switch from the non-syncytium-inducing
      (NSI) to the syncytium-inducing (SI) HIV virus phenotype. METHODS: For each of
      325 homosexual men in the Amsterdam Cohort Study, the slope of the CD3 T cell
      count versus time was determined. The timing (T cell inflection point (IP)) and
      magnitude of the change in slope were correlated with the time of the NSI/SI
      switch. RESULTS: Median T cell slopes before the IP (pre-IP) were nearly zero
      regardless of whether AIDS occurred; the slopes after the IP (post-IP) were
      associated with clinical outcomes, with a median annual decline of 17.6% among
      those who developed AIDS and increase of 4.6% in those remaining AIDS free. Among
      subjects considered to have a true IP (decline > 8.2%/year post-IP), the times of
      the SI switch and the IP slope were highly correlated (r = 0.65); among those
      with AIDS, the SI switch preceded the IP by a median of 0.63 years. CONCLUSION:
      These results support the concept of blind T cell homeostasis and also suggest
      that HIV-1 SI variants play an important role in the failure of T cell
      homeostasis.

PMID- 10894280
TI  - Changes in the natural history of cytomegalovirus retinitis following the
      introduction of highly active antiretroviral therapy.
AB  - OBJECTIVE: To determine the effect of highly active antiretroviral therapy
      (HAART) on the natural history of cytomegalovirus (CMV) retinitis. DESIGN AND
      PARTICIPANTS: Retrospective analysis of 103 consecutive patients diagnosed with
      CMV retinitis between 1990 and 1998. SETTING: Specialist HIV medicine department
      of a London hospital. MAIN OUTCOME MEASURES: Incidence of CMV retinitis, time to
      death following diagnosis, episodes of progression, incidence of inflammatory
      complications. The date of first use of HAART was January 1995. Data were
      censored on 30 June 1998. RESULTS: The incidence of CMV retinitis has declined
      dramatically following the introduction of HAART. Survival following CMV
      retinitis increased from a median of 0.65 years prior to 1995 to a median of 1.07
      years after this date (P = 0.004). In multivariate analyses HAART was
      independently associated with improved survival (P = 0.02) and the association
      with year of diagnosis was no longer significant, suggesting that this effect is
      predominantly due to HAART. None of the patients receiving HAART experienced
      progression after 6 months of treatment. Complications of retinitis such as
      retinal detachment, uveitis and optic atrophy occurred in 39% of patients. The
      rare inflammatory complications of vitritis and cystoid macular oedema occurred
      only in recipients of HAART. CONCLUSIONS: The introduction of HAART has had a
      major impact on the natural history of CMV retinitis with improved survival time
      and decreased risk of progression following diagnosis. However, immune
      reconstitution may be associated with inflammatory complications which can result
      in significant visual loss in the absence of active CMV disease.

PMID- 10894281
TI  - A randomised, open-label comparison of three highly active antiretroviral therapy
      regimens including two nucleoside analogues and indinavir for previously
      untreated HIV-1 infection: the OzCombo1 study.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) including two nucleoside
      analogues and a potent protease inhibitor is standard of care initial therapy for
      HIV-infected adults. The best-tolerated and most potent initial HAART regimen is
      unknown and was investigated in this study. METHODS: One hundred and nine HIV
      infected adults with no prior antiretroviral therapy, and CD4 lymphocyte counts <
      500 x 10(6) cells/l or plasma HIV RNA > 30,000 copies/ml were randomized to
      zidovudine-lamivudine-indinavir (ZDV-3TC-IDV), stavudine-lamivudine-indinavir
      (d4T-3TC-IDV) or stavudine-didanosine-indinavir (d4T-ddI-IDV) for 52 weeks. The
      primary endpoints were plasma HIV RNA and drug-related adverse events. Other
      assessments were overall safety, adherence and adverse events, CD4 lymphocyte
      counts, cutaneous delayed type hypersensitivity (DTH) responses and quality of
      life (Euroqol). RESULTS: Only 58% patients had HIV RNA < 50 copies/ml plasma at
      12 months, with no significant difference between the three regimes (P = 0.34).
      Drug-related adverse events sufficiently severe to warrant drug discontinuation
      were less common (P = 0.06) in patients receiving d4T-3TC-IDV (18%) than in those
      receiving ZDV-3TC-IDV (34%) or d4T-ddI-IDV (41%). The percentages of patients who
      remained on their assigned therapy with plasma HIV RNA < 50 copies/ml at 52 weeks
      were 60% with d4T-3TC-IDV, 53% with ZDV-3TC-IDV and 35% with d4T-ddI-IDV.
      Virological failure at 52 weeks was more likely in those whose adherence was
      estimated to be < 100% in the first 4 weeks of therapy (P = 0.02), but not in
      those who developed grade 3 or 4 drug-related adverse events. At 52 weeks, the
      mean CD4 lymphocyte count increase was 200 x 10(6) cells/l with only 7% of
      patients having counts lower than at baseline; DTH responses improved but
      remained clinically impaired in most patients. Quality of life improved
      significantly in all groups. CONCLUSIONS: Initial HAART regimens including IDV
      failed to suppress plasma HIV RNA to < 50 copies/ml in > 40% patients after only
      12 months of therapy although there was significant overall improvement
      immunologically and in quality of life. The type of dual nucleoside combination
      used was less important in predicting virological failure than was imperfect
      adherence early in therapy. Consideration should be given to modifying a HAART
      regimen relatively early in non-adherent patients.

PMID- 10894282
TI  - Efficacy and safety of twice daily first-line ritonavir/indinavir plus double
      nucleoside combination therapy in HIV-infected individuals. German
      Ritonavir/Indinavir Study Group.
AB  - OBJECTIVE: To evaluate the virological efficacy and safety of quadruple therapy
      with two nucleoside analogues and ritonavir (400 mg twice daily) plus indinavir
      (400 mg twice daily) combination in antiretroviral therapy-naive patients. DESIGN
      AND METHODS: An open-label, uncontrolled multicentre trial. Antiretroviral
      therapy-naive patients (n = 90) with high median baseline HIV RNA levels of
      220,000 copies/ml (range, 36,000-2,943,000 copies/ml) and median CD4 cell count
      of 189 x 10(6)/l (range, 4-656 x 10(6)/l) were started on a twice daily regimen
      of either zidovudine/lamivudine (49%), stavudine/lamivudine (38%) or
      stavudine/didanosine (13%) plus ritonavir 400 mg twice daily and indinavir 400 mg
      twice daily combination therapy. CD4 cell counts and HIV RNA were determined at
      weeks 0, 4, 8, 12, 16, 20, and 24. Statistical analysis was performed on
      treatment as well as intent-to-treat, where missing values were accounted for as
      failure. RESULTS: In the intent-to-treat analysis at week 24, the proportion of
      patients with HIV RNA of < 500 copies/ml, and < 80 copies/ml was 86.7% and 71.1%,
      respectively. In the on-treatment analysis at week 24, 80.0% of patients had
      undetectable viral load in the ultrasensitive assay (< 80 copies/ml; n = 80). The
      quadruple therapy was well tolerated except for mild diarrhoea, initial nausea
      and increased triglyceride levels. Treatment was stopped in seven (7.7%) patients
      because of adverse events and three (3.3%) were lost to follow-up. CONCLUSIONS:
      Our preliminary data suggest that the protease inhibitor combination
      ritonavir/indinavir plus double nucleoside therapy appears to be effective and
      safe in short-term treatment (up to 24 weeks).

PMID- 10894283
TI  - Enhanced penetration of indinavir in cerebrospinal fluid and semen after the
      addition of low-dose ritonavir.
AB  - OBJECTIVE: Penetration of antiretroviral drugs into anatomical HIV-1 reservoirs
      such as the male genital tract and the central nervous system is important. Data
      on indinavir (IDV) concentrations in seminal plasma are lacking and IDV
      concentrations in cerebrospinal fluid are at best borderline. DESIGN: Thirteen
      patients were treated with zidovudine (or stavudine), lamivudine, abacavir,
      nevirapine and IDV (1000 mg three times daily). When nevirapine led to low IDV
      concentrations, IDV was changed into the combination IDV/ritonavir (RTV) 800/100
      mg twice daily to improve the pharmacokinetic profile of IDV. METHODS: A serum
      pharmacokinetic profile, a semen sample and a cerebrospinal fluid sample were
      collected at weeks 8, 24, 48 and 72. RESULTS: Addition of RTV increased the
      median IDV trough concentration in serum from 65 to 336 ng/ml (P = 0.005). Median
      IDV concentration in seminal plasma increased from 141 to 1634 ng/ml (P = 0.002)
      (n = 9) and in cerebrospinal fluid from 39 (n = 12) to 104 (n = 7) ng/ml (P <
      0.001). In six patients with samples collected both before and after the addition
      of RTV, the IDV concentration in seminal plasma increased 8.2 times [95%
      confidence interval (CI) 5.2-11.6], and in cerebrospinal fluid 2.4 times (95% CI
      1.8-3.9). CONCLUSIONS: IDV penetrates well into the male genital tract. The
      addition of low-dose RTV not only increases IDV concentrations in serum but also
      in seminal plasma and cerebrospinal fluid, thereby probably improving the potency
      of the regimen in these anatomical HIV reservoirs. Higher serum trough levels
      alone can not sufficiently explain the observed increases in seminal plasma and
      cerebrospinal fluid concentrations. Inhibition of P-glycoprotein-mediated
      transport by RTV might be an additional mechanism.

PMID- 10894284
TI  - Absence of zidovudine resistance in antiretroviral-naive patients following
      zidovudine/lamivudine/protease inhibitor combination therapy: virological
      evaluation of the AVANTI 2 and AVANTI 3 studies.
AB  - OBJECTIVES: To assess the role of resistance mutations in subjects experiencing
      virological failure on zidovudine (ZDV) and lamivudine (3TC) combined with a
      protease inhibitor (PI) to those failing on ZDV/3TC alone. DESIGN AND METHODS:
      Samples were obtained from previously antiretroviral therapy-naive subjects
      enrolled into two studies, AVANTI 2 and AVANTI 3. Subjects were randomized to
      receive either: ZDV/3TC or ZDV/3TC plus indinavir (IDV) for 52 weeks (AVANTI 2),
      and ZDV/3TC or ZDV/3TC and nelfinavir (NFV) for 28 weeks (AVANTI 3). Emergence of
      viral resistance mutations was monitored by population sequencing and phenotypic
      resistance was determined by the recombinant virus assay. RESULTS: Genotypic data
      were obtained for subjects with plasma HIV-1 RNA > 400 copies/ml. In AVANTI 2,
      ZDV mutations were detected in 27% of ZDV/3TC-treated patients at week 52, but
      were absent in subjects treated with ZDV/3TC/IDV. No subjects from either arm of
      AVANTI 3 developed ZDV resistance mutations at week 28. The M184V mutation
      developed in most ZDV/3TC-treated subjects from both studies. The presence of
      M184V was, however, associated with significantly lower plasma viral RNA levels
      when compared with values obtained before initiation of treatment. There was a
      high frequency (4 of 11) of the protease L10F substitution in ZDV/3TC/IDV-treated
      patients that was associated with virological failure but did not result in
      phenotypic resistance to any of the PIs tested. CONCLUSIONS: ZDV mutations were
      not detected in ZDV/3TC/PI-treated patients and they developed slowly in those
      treated with ZDV/3TC. Few protease mutations known to confer phenotypic PI
      resistance developed in the ZDV/3TC/PI arms of either study. The low prevalence
      of ZDV and PI mutations is encouraging regarding the future treatment options of
      these patients.

PMID- 10894285
TI  - Phenotypic and genotypic analysis of clinical HIV-1 isolates reveals extensive
      protease inhibitor cross-resistance: a survey of over 6000 samples.
AB  - OBJECTIVE: To evaluate in HIV-1 the extent of phenotypic and genotypic
      antiretroviral drug resistance and cross-resistance towards the protease
      inhibitors (PIs) saquinavir, ritonavir, indinavir and nelfinavir among a set of
      patient samples originating from European and US routine clinical practice and
      submitted for phenotypic drug resistance testing and/or genotypic analysis. The
      mutational pattern(s) underlying both resistance and cross-resistance to PIs was
      investigated. METHOD: Over 6000 patient isolates with plasma viral load greater
      than 1000 copies/ml plasma were analysed. Phenotypic resistance was evaluated by
      a recombinant virus assay. Phenotypic resistance is expressed as the fold
      increase of the 50% inhibitory concentration (IC50) value of a compound for a
      patient-derived recombinant virus isolate compared with that for a wild-type
      laboratory virus. Genotypic analysis is reported as amino acid changes at
      positions in the HIV-1 protease compared to a wild-type reference. RESULTS:
      Phenotypic resistance to any single PI was observed in 17 to 25% of the clinical
      isolates investigated. Phenotypic cross-resistance among PIs (> 10-fold increase
      in IC50 value) was detected in 59 to 80% of the samples resistant (> 10-fold
      increase in IC50 value) to at least one PI. The prevalent mutations in PI
      resistant isolates involved substitutions at codons 10, 36, 46, 54, 71, 77, 82
      and 90. The most frequent mutational pattern in samples with PI cross-resistance
      involved combined substitutions at positions 10 and 90, extended with
      substitutions at positions 54, 71, 77, 82 or 84. CONCLUSIONS: Extensive use of
      first-generation PIs leads to the emergence of HIV-1 isolates possessing cross
      resistance to all members of this class. Identification of particular mutational
      profiles among these isolates may assist in the design of new generation
      inhibitors with specific activity against protease-mutant HIV strains.

PMID- 10894286
TI  - Efficacy and safety of famciclovir for treating mucocutaneous herpes simplex
      infection in HIV-infected individuals. Collaborative Famciclovir HIV Study Group.
AB  - OBJECTIVE: To compare the efficacy and safety of 7 days' treatment with
      famciclovir 500 mg twice a day versus acyclovir 400 mg five times a day, for
      mucocutaneous herpes simplex virus (HSV) infection in HIV-infected individuals.
      DESIGN: Randomized, double-blind, parallel-group study to demonstrate equivalence
      for the primary efficacy parameter. SETTING: Forty-eight hospital-based or
      specialist public-health clinics in 12 countries. PATIENTS: Two-hundred and
      ninety-three HIV-positive patients with recurrent HSV infection (orolabial or
      genital) starting treatment within 48 h of first appearance of herpetic lesions.
      MAIN OUTCOME MEASURES: Proportion of patients developing new lesions during
      treatment (primary outcome measures); Time to complete healing of lesions, time
      to cessation of viral shedding, time to loss of lesion-associated symptoms,
      number of withdrawals due to treatment failure (secondary outcome measures).
      RESULTS: Equivalence was defined prospectively and famciclovir was equivalent to
      acyclovir in preventing new lesion formation: new lesions occurred in 16.7% and
      13.3% of patients, respectively [difference, 3.4%; 95% confidence interval (CI), 
      4.8-11.5]. The groups were comparable in time to complete healing (median 7 days
      for both groups; hazard ratio, 1.01; 95% CI, 0.79-1.29; P = 0.95), cessation of
      viral shedding (median of 2 days [hazard ratio = 0.93; 95% C.I. 0.68, 1.27; p =
      0.64]), and loss of lesion-associated symptoms (median 4 days; hazard ratio,
      0.99; 95% CI, 0.75-1.30; P = 0.93). Similar numbers in each group withdrew
      because of treatment failure. There were no differences between groups in the
      incidence of adverse events. CONCLUSIONS: Famciclovir given twice a day is as
      effective and well tolerated as high-dose acyclovir for mucocutaneous HSV
      infections in HIV-infected individuals, and has the convenience of less frequent
      dosing.

PMID- 10894287
TI  - Impact of pulmonary tuberculosis on survival of HIV-infected adults: a
      prospective epidemiologic study in Uganda.
AB  - BACKGROUND: Retrospective cohort studies of tuberculosis suggest that active
      tuberculosis accelerates the progression of HIV infection. The validity of these
      findings has been questioned because of their retrospective design, diverse study
      populations, variable compliance with anti-tuberculous therapy and use of anti
      retroviral medication. To assess the impact of tuberculosis on survival in HIV
      infection we performed a prospective study among HIV-infected Ugandan adults with
      and without tuberculosis. METHODS: In a prospective cohort study, 230 patients
      with HIV-associated tuberculosis and 442 HIV-infected subjects without
      tuberculosis were followed for a mean duration of 19 months for survival. To
      assess changes in viral load over 1 year, 20 pairs of tuberculosis cases and
      controls were selected and matched according to baseline CD4 lymphocyte count,
      age, sex and tuberculin skin test status. RESULTS: During the follow-up period,
      63 out of of 230 tuberculosis cases (28%) died compared with 85 out of 442
      controls (19%), with a crude risk ratio of 1.4 [95% confidence interval (CI),
      1.07-1.87]. Most deaths occurred in patients with CD4 lymphocyte counts < 200 x
      10(6) cells/l at baseline (n = 99) and occurred with similar frequency in the
      tuberculosis cases (46%) and the controls (44%). When the CD4 lymphocyte count
      was > 200 x 10(6)/l, however, the relative risk of death in HIV-associated
      tuberculosis was 2.1 (95% CI, 1.27-3.62) compared with subjects without
      tuberculosis. For subjects with a CD4 lymphocyte count > 200 x 10(6)/l, the 1
      year survival proportion was slightly lower in the cases than in the controls
      (0.91 versus 0.96), but by 2 years the survival proportion was significantly
      lower in the cases than in the controls (0.84 versus 0.91; P < 0.02; log-rank
      test). For subjects with a CD4 lymphocyte count of 200 x 10(6) cells/l or fewer,
      the survival proportion at 1 year for the controls was lower than cases (0.59
      versus 0.64), but this difference was not statistically significant (P = 0.53;
      logrank test). After adjusting for age, sex, tuberculin skin test status, CD4
      lymphocyte count, and history of HIV-related infections, the overall relative
      hazard for death associated with tuberculosis was 1.81 (95% CI, 1.24-2.65). In a
      nested Cox regression model, the relative hazard for death was 3.0 (95% CI, 1.62
      5.63) for subjects with CD4 lymphocyte counts > 200 x 10(6)/l and 1.5 (95% CI,
      0.99-2.40) for subjects with a CD4 lymphocyte count of 200 x 10(6)/l or fewer.
      CONCLUSION: The findings from this prospective study indicate that active
      tuberculosis exerts its greatest effect on survival in the early stages of HIV
      infection, when there is a reserve capacity of the host immune response. These
      observations provide a theoretical basis for the treatment of latent tuberculous
      infection in HIV-infected persons.

PMID- 10894288
TI  - Antiretroviral medication use among injection drug users: two potential futures.
AB  - OBJECTIVE: To model the potential impact of HIV infection rates and the use of
      antiretroviral medication on life expectancy and mortality in the Downtown
      Eastside of Vancouver, British Columbia, Canada, from 1999 to 2006. DESIGN:
      Population projections were made to estimate the population of the Downtown
      Eastside in the year 2006. METHODS: Two scenarios were modelled to predict the
      impact of HIV infection and antiretroviral use on mortality and life expectancy.
      The use of antiretroviral therapy was estimated to be 80% in the first scenario
      and 20% in the second. The prevalence of HIV by age and sex, and by year infected
      was estimated using data from the Vancouver Injection Drug User Study. RESULTS:
      If the level of antiretroviral therapy use among HIV-positive individuals was 80%
      at baseline, then we estimate that the life expectancy at birth in the year 2006
      will be 60.8 years for men and 72.8 years for women, and 172 AIDS deaths will
      occur between 1999 and 2006. In contrast, if the present level of antiretroviral
      medication use persists, the life expectancy at birth in the year 2006 will be
      56.9 years for men and 68.6 years for women, and 503 AIDS deaths will occur
      between 1999 and 2006. CONCLUSION: Our analysis suggests that if the low levels
      of antiretroviral therapy use persist, life expectancy in Vancouver's Downtown
      Eastside will soon be on a par with many of the world's least developed
      countries. Our findings highlight the large health status decline that can be
      expected in many inner city neighbourhoods if low levels of antiretroviral use
      persist. Although reasonable coverage targets for injection drug users (IDU) have
      not been established, the expanded use of antiretroviral medication is urgently
      needed to avert a drastic decline in health status.

PMID- 10894289
TI  - HIV/AIDS among African Americans: progress or progression?
AB  - OBJECTIVES: To review data on the extent of HIV infection and associated risk
      behaviors, the occurrence of AIDS, and HIV-related mortality in African Americans
      and to suggest what can be done to reduce HIV exposure and infection in this
      population. DESIGN/METHODS: Review of epidemiologic, published, multisite data on
      HIV infection in, and related behaviors of, African Americans. RESULTS: On every
      epidemiologic measure in common use, African Americans, compared with the four
      other federally recognized racial/ethnic groups, have the most severe epidemic.
      The trend data show continuing growth in the African American epidemic despite
      the availability of effective behavioral interventions and biomedical treatments.
      Few published intervention studies with African American populations have been
      adequately evaluated; nor have they focused proportionately on men who have sex
      with men, a group in the African American community with continuing high rates of
      infection. CONCLUSIONS: Rates of HIV transmission and disease among African
      Americans are high, disproportionate, and are not declining as significantly in
      response to effective interventions as they are among whites. Attention is
      urgently needed to increase our understanding of risk behaviors, social networks,
      and specific factors in the African American community that can be altered to
      reduce HIV infection. Macroenvironmental factors--poverty, social class, racism-
      need to be studied to suggest possible intervention components to reduce rates of
      HIV transmission and to increase the use of therapies that are more effectively
      slowing disease progression and lowering death rates among whites.

PMID- 10894290
TI  - A randomized trial of hierarchical counseling in a short, clinic-based
      intervention to reduce the risk of sexually transmitted diseases in women.
AB  - INTRODUCTION: Effective public health interventions to reduce the incidence of
      sexually transmitted disease (STD), including HIV, among women are urgently
      needed. METHODS: A randomized trial among STD clinic patients of two types of
      counseling regarding methods to reduce disease transmission: a 'hierarchical'
      message (HP), with counseling on male condoms, female condoms, diaphragms,
      cervical caps, and spermicides (three formulations) and a single method message
      (SM) covering male condoms only or female condoms only. For this analysis, 1591
      subjects received one of three educational messages at the central public STD
      clinic in Philadelphia. Disease incidence data for up to 6 months following the
      index visit were extracted from the clinic's electronic database. The primary
      outcome was STD reinfection: laboratory-confirmed trichomonas infection and/or
      clinical diagnoses of at least one of four STD. Rates were based on the full
      sample of randomized women (full sample) and on the subset who spontaneously
      returned between 22 days and 183 days following their initial visit (returners).
      RESULTS: Rates of trichomonas infection (SM 2.5% full sample and 12.9% returners
      versus HP 2.4% full sample and 11.5% returners) and clinical diagnoses (SM 6.3%
      full sample and 39.7% returners versus HP 6.9% full sample and 41.2% returners)
      did not differ across the two arms of the randomized trial, both as a straight
      percentage and in survival analysis (P = .81). CONCLUSION: At least in this
      single-session intervention trial, increasing choices in protection for women did
      not produce a change in disease risk compared with single-method approaches.

PMID- 10894291
TI  - Cost-threshold analyses of the National AIDS Demonstration Research HIV
      prevention interventions.
AB  - OBJECTIVE: The goal of the multisite National AIDS Demonstration Research (NADR)
      program was to reduce the sexual and drug injection-related HIV risks of out-of
      treatment injection drug users and their sex partners. Previous analyses have
      established that the NADR interventions were effective at changing participants'
      risky behaviors. This study was to determine whether the NADR program also was
      cost-effective. METHODS: Data from eight NADR study sites were included in the
      analysis. A mathematical model was used to translate reported sexual and
      injection-related behavior changes into an estimate of the number of infections
      prevented by the NADR interventions and then to calculate the corresponding
      savings in averted HIV/AIDS medical care costs and quality-adjusted years of
      life, assuming United States values for these parameters. Because cost data were
      not collected in the original NADR evaluation, the savings in averted medical
      care costs were compared with the cost of implementing a similar intervention
      program for injection drug users. RESULTS: The eight NADR interventions prevented
      approximately 129 infections among 6629 participants and their partners. Overall,
      the NADR program would be cost saving (i.e. provide net economic savings) if it
      cost less than US$2107 per person and would be cost-effective if it cost less
      than US$10,264 per person. Both of these estimates are considerably larger than
      the US$273 per person cost of the comparison intervention. There was substantial
      cross-site variability. CONCLUSIONS: The results of this analysis strongly
      suggest that the NADR interventions were cost-saving overall and were, at the
      very least, cost-effective at all eight sites. In the United States and other
      developed counties, investments in HIV-prevention interventions such as these
      have the potential to save substantial economic resources by averting HIV-related
      medical care expenses among injection drug users.

PMID- 10894292
TI  - Differential trends in mortality from AIDS in men and women in Brazil (1984
      1995).
AB  - OBJECTIVE: To analyse trends in AIDS mortality in men and women in Brazil, for
      the period 1984-1995. DESIGN AND METHODS: National statistics on yearly numbers
      of reported deaths by cause, in conjunction with census population counts and
      inter-censory estimates, were used to calculate age- and sex-specific AIDS
      mortality rates for Brazil as a whole and for Sao Paulo and Rio de Janeiro, the
      two largest cities in Brazil, and those most affected by the AIDS epidemic to
      date. RESULTS: Numbers of reported deaths from AIDS have increased yearly in
      Brazil since 1984, to approximately 15,000 in 1995. The data suggest that after a
      very dramatic rise in mortality rates, the epidemic may have started to slow even
      before the introduction of freely available highly-active anti-retroviral
      therapy, although unequally in terms of both geographical and sex distributions.
      Women also tended to die at relatively younger ages than men in all areas
      studied, and by 1995 the impact of AIDS on overall mortality was practically the
      same for men and women aged 25-34 years (21% in Sao Paulo). CONCLUSIONS: Trends
      in mortality from AIDS in Brazil reflect both the geographical expansion of the
      epidemic outwards from its original epicentres, and the fact that women are
      becoming increasingly affected by the AIDS epidemic.

PMID- 10894293
TI  - HIV prevalence and strain diversity in Gabon: the end of a paradox.

PMID- 10894294
TI  - Low and stable HIV infection rates in Senegal?

PMID- 10894295
TI  - Mobile phone and interactive computer interviewing to measure HIV-related risk
      behaviours: the impacts of data collection methods on research results.

PMID- 10894296
TI  - Novel SDF-1 gene mutations in simians: presence of GG-AA transition in the 3'
      untranslated region.

PMID- 10894297
TI  - Elicitation of protective immunity against simian immunodeficiency virus
      infection by a recombinant Sendai virus expressing the Gag protein.

PMID- 10894298
TI  - Isolation of Mycobacterium interjectum in an AIDS patient with diarrhea.

PMID- 10894300
TI  - Steatosis-lactic acidosis syndrome associated with stavudine and lamivudine
      therapy.

PMID- 10894299
TI  - Onset of HIV-1 antibody production after highly active antiretroviral therapy in
      a seronegative HIV-1-infected child.

PMID- 10894301
TI  - Induction of P-glycoprotein expression by HIV protease inhibitors in cell
      culture.

PMID- 10894302
TI  - Protease inhibitor-related paronychia, ingrown toenails, desquamative cheilitis
      and cutaneous xerosis.

PMID- 10894303
TI  - Efavirenz decreases methadone blood concentrations.

PMID- 10894304
TI  - Frequency of multinucleoside analogue-resistant genotypes observed during
      antiretroviral therapy.

PMID- 10894305
TI  - Report of the Joint Working Group on Telemammography/Teleradiology and
      Information Management. Washington DC, USA. March 15-17, 1999.

PMID- 10894306
TI  - Report of the Working Group on Digital Mammography: Digital Displays and
      Workstation Design. Washington DC, USA. March 19-10, 1998.

PMID- 10894307
TI  - Report of the Joint Working Group on Quantitative In Vivo Functional Imaging in
      Oncology. Washington DC, USA. January 6-8, 1999.

PMID- 10894308
TI  - Urinary incontinence: does it increase risk for falls and fractures? Study of
      Osteoporotic Fractures Research Group.
AB  - OBJECTIVE: To determine if urge urinary incontinence is associated with risk of
      falls and non-spine fractures in older women. METHODS: Type and frequency of
      incontinent episodes were assessed by 6,049 community-dwelling women using a self
      completed questionnaire. Postcards were subsequently mailed every 4 months to
      inquire about falls and fractures. Incident fractures were confirmed by
      radiographic report. Logistic and proportional hazard models were used to assess
      the independent association of urge urinary incontinence and risk of falling or
      fracture. RESULTS: The mean age of the women was 78.5 (+/- 4.6) years. During an
      average follow-up of 3 years, 55% of women reported falling, and 8.5% reported
      fractures. One-quarter of the women (1,493) reported weekly or more frequent urge
      incontinence, 19% (1,137) reported weekly or more frequent stress incontinence,
      and 708 (12%) reported both types of incontinence. In multivariate models, weekly
      or more frequent urge incontinence was associated independently with risk of
      falling (odds ratio = 1.26; 95% confidence interval (CI), 1.14-1.40) and with non
      spine nontraumatic fracture (relative hazard 1.34; 95% CI, 1.06-1.69; P = .02).
      Stress incontinence was not associated independently with falls or fracture.
      CONCLUSIONS: Weekly or more frequent urge incontinence was associated
      independently with an increased risk of falls and non-spine, nontraumatic
      fractures in older women. Urinary frequency, nocturia, and rushing to the
      bathroom to avoid urge incontinent episodes most likely increase the risk of
      falling, which then results in fractures. Early diagnosis and appropriate
      treatment of urge incontinence may decrease the risk of fracture.

PMID- 10894309
TI  - Outcome and utilization differences for older persons with stroke in HMO and fee
      for-service systems.
AB  - OBJECTIVES: To compare treatment and outcomes for older persons with stroke in
      Medicare health maintenance organizations (HMOs) and fee-for-service (FFS)
      systems. DESIGN: Inception cohort stratified by payer and followed for 1 year.
      SETTING: Six HMOs and five FFS systems with large Medicare populations in the
      West, Midwest, and Eastern United States. PARTICIPANTS: A total of 429 randomly
      selected stroke patients receiving rehabilitation in nursing homes or
      rehabilitation hospitals (RHs) from June 1993 to June 1995. MEASUREMENTS:
      Improvement in activities of daily living (ADLs) during rehabilitation, and ADL
      recovery, community residence, and utilization until 12 months after stroke.
      Outcomes were adjusted for premorbid function, marital status, comorbid illness,
      posthospital function, cognition, psychological problems, and stroke deficits.
      RESULTS: At baseline, HMO patients were more likely to be married, and less
      likely to be blind or have psychiatric diagnoses. HMO patients had shorter
      hospitalizations (P < .001), were less likely to be admitted to RHs (13% vs 85%,
      P < .001), and received fewer therapy and physician specialist visits (P < .001)
      but more home health visits (P < .001). During rehabilitation, FFS patients made
      greater improvement in ADLs (difference, 0.73 ADLs; 95% CI, .37-1.09). At 1 year,
      there was no difference in ADL recovery (difference, -0.24 ADL; 95% CI, -0.64
      0.16), but FFS patients were more likely to reside in the community (adjusted OR,
      1.8; 95% CI, 1.1-3.1), and HMO patients were more likely to reside in nursing
      homes (adjusted OR, 2.4; 95% CI, 1.1-5.5). CONCLUSION: Study findings suggest
      that short-term functional outcomes and eventual community residence rates are
      poorer for Medicare HMO patients with stroke than for stroke patients receiving
      FFS care, consistent with the lower intensity of rehabilitation (in nursing homes
      vs RHs) and less specialty physician care.

PMID- 10894310
TI  - Racial differences in use of cancer prevention services among older Americans.
AB  - CONTEXT: Racial differences in receipt of cancer prevention services may be
      related to poorer outcomes for minorities. Understanding reasons for such
      differences could help target appropriate interventions. OBJECTIVES: To determine
      if racial differences exist in the use of cancer prevention services among older
      blacks and whites and to explore explanatory factors. DESIGN: Sixth follow-up
      survey of probability sample, four-stage stratified household design with 4,162
      at baseline in 1986-1987 and 2,846 surveyed in 1992-1993. SETTING: The Piedmont
      area of North Carolina. PARTICIPANTS: At time of follow-up survey in 1992-1993
      there were 1,486 women and 726 men age >70 years, of whom 1,246 were black and
      966 were white. MEASUREMENTS: Self-reported use of Papanicolou (pap) testing,
      clinical breast examination, mammography, rectal examination, and fecal occult
      blood testing on a regular basis within the last two years. RESULTS: Compared
      with older whites, older black persons are less likely to receive pap test (48.1%
      black vs 56.6% white, P < .001), clinical breast examination (64.6% black vs
      69.2% white, P < .007), mammography (30.2% black vs 40.5% white, P < .001),
      rectal examination (50.2% black vs 62.4% white, P < .001), and fecal occult blood
      testing (37.5% black vs 46.2% white, P < .001). Effect of race on receipt of
      cancer prevention services was not significant when levels of education, income,
      and insurance coverage were considered. CONCLUSION: Racial differences exist in
      the use of cancer prevention services among older Americans. However, these
      differences are related to educational, income, and insurance differences between
      blacks and whites.

PMID- 10894311
TI  - Gender differences in the treatment of cerebrovascular disease.
AB  - OBJECTIVE: Previous studies have shown that women receive fewer invasive
      procedures for the treatment of coronary artery disease than men, but gender
      differences in cerebrovascular disease have not been well studied. Our objective
      was to explore differences in the treatment of stroke between men and women.
      DESIGN: Secondary database analyses. STUDY PARTICIPANTS: We examined the use of
      carotid endarterectomy in a nationally representative sample of Medicare
      enrollees aged 65 to 84, hospitalized for a principal diagnosis of stroke in
      1992, the "all strokes group". We also studied a subgroup of patients, the
      "carotid disease subgroup", admitted with a principal diagnosis of precerebral
      arterial occlusion and stenosis or transient cerebral ischemia. MEASUREMENTS: We
      determined rates of carotid endarterectomy for the all strokes group within
      gender and age groups and calculated corresponding female-to-male relative risks
      (RR) and 95% confidence intervals (CI). We also performed similar analyses for
      the carotid disease subgroup. We then used logistic regression to estimate the
      relative risk of use of carotid endarterectomy for women, controlling for age and
      comorbidity. RESULTS: The all-strokes group consisted of 3,356 women and 2,927
      men, of whom 1,009 women and 990 men were in the carotid disease subgroup. The
      overall age-adjusted female-to-male relative risk of undergoing carotid
      endarterectomy for those aged 65 to 84 was 0.69 (95% CI, 0.64-0.74) in the all
      strokes group and 0.77 (95% CI, 0.72-0.82) in the carotid disease subgroup. In
      both analyses, the RR became more pronounced with increasing age. In the all
      strokes group, for example, the RR was 0.80 (0.70-0.92) for those aged 65 to 69
      and 0.39 (0.32-0.48) for those aged 80 to 84. The RR for the all strokes group
      remained similar in magnitude even after controlling for comorbidity (RR, 0.63
      and 95% CI, 0.59-0.70). CONCLUSION: We conclude that women hospitalized for
      strokes undergo fewer carotid endarterectomies than men. Further studies are
      needed to examine the reasons for and implications of this gender difference.

PMID- 10894312
TI  - Postmenopausal hormone therapy and cognitive function in healthy older women.
AB  - OBJECTIVE: Accumulating biologic evidence suggests that estrogen is related to
      cognitive function. Several epidemiologic investigations have reported that
      hormone therapy may reduce the risk of Alzheimer's disease. However, fewer
      studies have examined the relation of postmenopausal hormone use to general
      cognitive function in nondemented older women. Thus, we examined the association
      of hormone therapy to performance on four cognitive tests among healthy
      participants of the Nurses' Health Study. DESIGN: Cohort study. SETTING: The
      Nurses' Health Study, an ongoing prospective cohort study begun in 1976.
      PARTICIPANTS: From the Nurses' Health Study, 2138 women aged 70-78 years.
      MEASUREMENTS: From 1995-1999 we administered four cognitive tests (Telephone
      Interview for Cognitive Status (TICS), immediate and delayed recall of the East
      Boston Memory Test (EBMT), and verbal fluency) by telephone. Hormone use was
      ascertained from biennial questionnaires beginning in 1976. Linear and logistic
      regression models were used to calculate multivariate-adjusted differences in
      scores and relative risks of a low score for never users compared to current and
      past hormone users. RESULTS: After adjustment for confounders, neither current
      nor long-term hormone users demonstrated better performance on an overall measure
      of cognition (TICS), or on three tests of verbal memory (immediate and delayed
      recall of the EBMT, immediate recall of the TICS 10-word list) than never users.
      On the test of verbal fluency, current hormone users scored significantly better
      than never users (linear regression estimate of the difference in score = 0.78
      points, 95% confidence interval (CI) 0.19-0.38, P = .01 for any current use; and
      0.91 points, 95% CI 0.28-1.54, P = .005 for > or = 5 years current use). Current
      hormone users also had a 30% decrease (RR = 0.70, 95% CI 0.45-1.09) in their risk
      of a low score on the test of verbal fluency. These results were similar for
      women taking estrogen alone and estrogen combined with a progestin. CONCLUSIONS:
      Verbal fluency may be enhanced among women taking postmenopausal hormones,
      however, there is little support for better overall cognitive function in hormone
      users than nonusers.

PMID- 10894313
TI  - Effect of voluntary weight loss on bone mineral density in older overweight
      women.
AB  - OBJECTIVES: To examine the effect of diet and exercise-induced weight loss on
      bone mineral density in overweight postmenopausal women DESIGN: A 1-year
      prospective, randomized clinical trial. SETTING: Two university medical school
      research centers. PARTICIPANTS: Sixty-seven overweight postmenopausal women, a
      subset of the women who participated in the Trial of Nonpharmacological
      Interventions in the Elderly (TONE) to control hypertension. The participants
      were assigned randomly to one of four groups: usual care, weight loss only,
      sodium restriction only, or combined weight loss/sodium restriction.
      INTERVENTION: All TONE participants in the treatment groups attended regular
      dietary intervention sessions to lose weight, reduce sodium intake, or both that
      they might refrain from using antihypertensive medications for a period of 15 to
      36 months (median = 29 months). MEASUREMENTS: Bone mineral density (BMD) assessed
      by dual energy X-ray absorptiometry (DXA), serum and urine markers of bone
      metabolism, and other demographic and clinical data were collected at baseline, 6
      months, and 12 months. RESULTS: Women assigned to the weight loss interventions
      lost 9.2 +/- 1.2 lbs (mean +/- SE) at 6 months and 7.7 +/- 2.0 lbs at 12 months
      compared with 1.8 +/- 1.0 lbs at 6 months and 1.9 +/- 1.6 lbs at 12 months for
      those assigned to no weight loss intervention (P < .0001). Weight loss was
      correlated with a decrease in total body BMD (P = .004) and an increase in
      osteocalcin (P = .004) after controlling for baseline bone measures, intervention
      assignment, and other baseline covariates. Regression analyses indicated that
      total body BMD decreased by 6.25 +/- 2.06 g/cm2 x 10-4 for each pound of weight
      loss. CONCLUSIONS: Voluntary weight loss in overweight postmenopausal women is
      associated with modest decrease in total body BMD. Clinicians recommending weight
      loss for older postmenopausal women may need to include recommendations for
      reducing the risk of bone loss.

PMID- 10894314
TI  - Association between medication supplies and healthcare costs in older adults from
      an urban healthcare system.
AB  - OBJECTIVES: The amount of medication dispensed to older adults for the treatment
      of chronic disease must be balanced carefully. Insufficient medication supplies
      lead to inadequate treatment of chronic disease, whereas excessive supplies
      represent wasted resources and the potential for toxicity. We used an electronic
      medical record system to determine the distribution of medications supplied to
      older urban adults and to examine the correlations of these distributions with
      healthcare costs and use. DESIGN: A cross-sectional study using data acquired
      over 3 years (1994-1996). SETTING: A tax-supported urban public healthcare system
      consisting of a 300-bed hospital, an emergency department, and a network of
      community-based ambulatory care centers. PATIENTS: Patients were >60 years of age
      and had at least one prescription refill and at least two ambulatory visits or
      one hospitalization during the 3-year period. MEASUREMENTS: Focusing on 12 major
      categories of drugs used to treat chronic diseases, we determined the amounts and
      direct costs of these medications dispensed to older adult patients. Amounts of
      medications that were needed by patients to medicate themselves adequately were
      compared with the medication supply actually dispensed considering all sources of
      care (primary, emergency, and inpatient). We calculated the excess drug costs
      attributable to oversupply of medication (>120% of the amount needed) and the
      drug cost reduction caused by undersupply of medication (<80% of the amount
      needed). We also compared total healthcare use and costs for patients who had an
      oversupply, an undersupply, or an appropriate supply of their medications.
      RESULTS: The cohort comprised 4164 patients with a mean age of 71 +/- 7 (SD) who
      received a mean of 3 +/- 2 (SD) drugs for chronic conditions. There were 668
      patients (16%) who received <80% of the supply needed, 1556 patients (37%) who
      received between 80 and 120% of the supply needed, and 1940 patients (47%) who
      received >120% of the supply needed. The total direct cost of targeted
      medications for 3 years was $1.96 million or, on average, $654,000 annually.
      During the 3-year period, patients receiving >120% of their needed medications
      had excess direct medication costs of $279,084 or $144 per patient, whereas
      patients receiving <80% of drugs needed had reduced medication costs of $423,438
      or $634 per patient. Multivariable analyses revealed that both under- and over
      supplies of medication were associated with a greater likelihood of emergency
      department visits and hospital admissions. CONCLUSIONS: More than one-half of the
      older adults in our study have under- or over-supplies of medications for the
      treatment of their chronic diseases. Such inappropriate supplies of medications
      are associated with healthcare utilization and costs.

PMID- 10894315
TI  - The relationship between alcohol problems and health functioning of older adults
      in primary care settings.
AB  - OBJECTIVE: The purpose of this study was to determine the relationship between
      alcohol use and health functioning in a sample of older adults screened in
      primary care settings. DESIGN: A cross-sectional study. SETTING: Thirty-seven
      primary care clinics. PARTICIPANTS: Older adults (n = 8,578; aged 55-97) with
      regularly scheduled appointments in primary care clinics were screened.
      MEASUREMENTS: Participants were categorized based on alcohol consumption levels
      as abstainers, low-risk drinkers, and at-risk drinkers (women: 9 or more
      drinks/week; men: 12 or more drinks/week). Dependent variables were eight SF-36
      health functioning scales. RESULTS: Sixty-one percent of participants were
      abstainers, 31% were low-risk drinkers, and 7% were at-risk drinkers. ANCOVAs
      found significant effects of drinking status on General Health, Physical
      Functioning, Physical Role Functioning, Bodily Pain, Vitality, Mental Health,
      Emotional Role, and Social Functioning, controlling for age and gender, with low
      risk drinkers scoring significantly better than abstainers. At-risk drinkers had
      significantly poorer mental health functioning than low-risk drinkers. Few
      significant gender differences were found on SF-36 scales. CONCLUSIONS: Older
      adults who are at-risk drinkers may not present with poor physical health
      functioning. Future studies are needed to determine the relationship between
      drinking limits for older adults and other areas of physical and psychosocial
      health.

PMID- 10894316
TI  - Cognitive impairment without dementia in older people: prevalence, vascular risk
      factors, impact on disability. The Italian Longitudinal Study on Aging.
AB  - OBJECTIVES: To investigate prevalence of "cognitive impairment, no dementia"
      (CIND) in the Italian older population, evaluating the association with
      cardiovascular disease and the impact on activities of daily living (ADL). CIND
      may provide pathogenic clues to dementia and independently affect ADL. DESIGN:
      Cross-sectional examination in the context of the Italian Longitudinal Study on
      Aging. SETTING: Random population sample from eight Italian municipalities.
      PARTICIPANTS: A total of 3,425 individuals aged 65-84 years, residing in the
      community or institutionalized. MEASUREMENTS: Study participants were screened
      for cognitive impairment by using the Mini-Mental State Examination. Trained
      neurologists examined those scoring <24. CIND diagnosis relied on clinical and
      neuropsychological examination, informant interview, and assessment of functional
      activities. Age-related cognitive decline (ARCD) was diagnosed in CIND cases
      without neuropsychiatric disorders responsible for the cognitive impairment.
      RESULTS: Prevalence was 10.7% for CIND and 7.5% for ARCD, increased with age, and
      was higher in women. Age (odds ratio [OR], 1.09; 95% confidence interval [CI],
      1.06-1.12), stroke (OR, 2.05; 95% CI, 1.26-3.35) and heart failure (OR, 1.73; 95%
      CI, 1.11-2.68) were significantly and positively associated with CIND at
      multivariate analysis. Education (OR, 0.61; 95% CI, 0.56-0.65) and smoking (OR,
      0.72; 95% CI, 0.54-0.98) showed a negative correlation. Age and myocardial
      infarction were positively associated with ARCD, whereas a negative correlation
      was found for education and smoking. The effect of smoking was no more
      significant either on CIND or ARCD considering current habits or "pack year"
      exposure. CIND showed an independent impact on ADL (OR, 1.88; 95% CI, 1.41-2.49).
      CONCLUSIONS: CIND is very frequent in older people. The effect of demographic
      variables and vascular conditions offers opportunities for prevention. The
      association with functional impairment is useful to evaluate the burden of
      disability and healthcare demands.

PMID- 10894317
TI  - A high diagnostic rate in older patients attending an integrated syncope clinic.
AB  - OBJECTIVES: To describe the findings in the first year of an integrated syncope
      clinic for older patients and to review the published literature on "integrated"
      syncope clinics investigating older people. DESIGN: Review of syncope clinic
      database and Medline search for relevant literature. SETTING: Outpatient syncope
      clinics in two district hospitals in the same city. PARTICIPANTS: Secondary
      referrals from the in- and outpatient population with recurrent unexplained
      presyncopal and syncopal symptoms. RESULTS: The results of testing in 76 patients
      over the age of 60 years were available for analysis. A diagnosis was achieved in
      67 (88%) of the patients with 76% of the diagnoses being cardiovascular in
      origin. The prevalence rates of neurocardiogenic syncope (32%) and carotid sinus
      syndrome (17%), however, differed from previously reported rates. CONCLUSIONS:
      Evaluation of presyncopal and syncopal events in an "integrated syncope clinic"
      achieves a high diagnostic yield in older subjects.

PMID- 10894318
TI  - Effect of aging on the relationship between multiple risk factors and waist
      circumference.
AB  - OBJECTIVE: To examine the relationship between various coronary risk factors and
      the different levels of fat distribution in younger (<65 years) and older (> or =
      65 years) men and women, using the classifications proposed by the National
      Heart, Lung and Blood Institute (NHLBI) and the World Health Organization (WHO).
      DESIGN: Cross-sectional study of subjects enrolled in the Baltimore Longitudinal
      Study of Aging. MEASUREMENTS: Systolic blood pressure, diastolic blood pressure,
      fasting glucose, 2-hour glucose, fasting insulin, homeostasis model assessment
      insulin resistance (HOMAIR), triglyceride, total cholesterol, high-density
      lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol were
      measured as risk factors. The proportion of subjects with abnormal risk factor
      levels by waist circumference classifications was determined in the age and
      gender subgroups. RESULTS: There were significant adverse effects of age per se
      on all risk factors with the exception of fasting insulin and HOMAIR in both men
      and women, total cholesterol in men, and diastolic blood pressure in women. HDL
      cholesterol was higher in older subjects. There were significant correlations
      between waist circumference and all of the risk factors in the younger group.
      Waist circumference did not have a significant correlation with total cholesterol
      in older men, or with total cholesterol and LDL-cholesterol in older women. The
      proportion of subjects with an abnormal risk factor level increased with
      increasing waist circumference for most risk factors in both younger and older
      subjects, but proportions of subjects in each individual waist group were higher
      in older than in younger groups for systolic blood pressure, diastolic blood
      pressure, fasting glucose, and 2-hour glucose in men, and for systolic blood
      pressure, fasting glucose, 2-hour glucose, total and LDL-cholesterol, and
      triglyceride in women. CONCLUSIONS: Our data indicate that the waist
      circumference cutpoints proposed by NHLBI and WHO standards are useful for the
      prediction of cardiovascular disease risk factors in older as well as in younger
      men and women.

PMID- 10894319
TI  - Subcutaneous fluid infusion in a long-term care setting.
AB  - OBJECTIVE: To study the use of hypodermoclysis in a long-term care setting for
      chronic fluid supplementation and to compare it to intravenous (IV) fluid in the
      treatment of acute mild to moderate dehydration. DESIGN: A prospective
      observational study. PARTICIPANTS: Fifty-five residents of a long-term care
      facility treated with fluid therapy during a 5-week period. MAIN OUTCOME
      MEASURES: Efficacy of hydration and adverse effects were obtained from detailed
      chart review, interviews with healthcare providers, and investigators'
      observations. RESULTS: The study subjects were frail older people.
      Hypodermoclysis was used for maintenance fluid needs in 24 residents; none of
      these residents required any additional fluid therapy for dehydration. In
      addition, 37 residents received fluids for acute dehydration. In these residents,
      hypodermoclysis was associated with clinical improvement in 57% and no clinical
      change in 25%. Recipients of IV fluids improved 81% of the time and the remainder
      were unchanged. Hypodermoclysis was associated with fewer fluid therapy-related
      complications relative to IV therapy (P = .04). CONCLUSIONS: Hypodermoclysis is
      an effective procedure for providing fluids for both chronic maintenance needs
      and acute situations associated with mild to moderate dehydration in a long-term
      care setting. Hypodermoclysis appears safer and can avoid transfers to hospital
      for rehydration.

PMID- 10894320
TI  - Association of Alzheimer's disease and smoking: the case for sibling controls.
AB  - OBJECTIVES: To study the association between cigarette smoking and Alzheimer's
      Disease (AD). DESIGN: Intrafamily case-control, with sibling controls and a
      variable number of controls per case. SETTING: AD cases were identified through
      the Research Registry of the University Hospitals of the Cleveland/Case Western
      Reserve University Alzheimer Center. PARTICIPANTS: Study subjects were 86
      probable AD cases (index cases) and all of their full siblings, alive or dead,
      aged > or = 50 years, a total of 238 subjects. MEASUREMENTS: Exposure for each
      individual was ascertained with a questionnaire answered by several informants.
      Cognitive status of siblings of the AD cases (impaired or intact) was ascertained
      by telephone using validated instruments. Diagnosis of dementia in cognitively
      impaired siblings of index cases was not attempted. RESULTS: Chi-square analysis
      tested for departure from a random distribution of disease across smokers and
      nonsmokers within families. No significant departure was found utilizing all
      families (P > .40) nor utilizing those families where only the index case was
      affected (P > .90). Conditional logistic regression evaluated the association
      within families, controlling for age, sex, and education. Analyses both included
      and excluded secondary cases of cognitive impairment. No association was found
      between smoking and disease (OR = 1.26; 95% confidence interval, 0.66-2.42, and
      OR = 1.42; 95% confidence interval, 0.69-2.89, respectively). CONCLUSIONS: No
      significant association was found between smoking and cognitive status. Further,
      analyses based on the comparison of persons with AD with their unaffected
      siblings also suggest that smoking does not decrease the risk of AD.

PMID- 10894322
TI  - Long-term continuous use of benzodiazepines by older adults in Quebec:
      prevalence, incidence and risk factors.
AB  - OBJECTIVE: To determine the prevalence and incidence of long-term use of
      benzodiazepines and to assess patient-, prescriber-, and drug-related risk
      factors. DESIGN: Cohort study. PARTICIPANTS: 1,423 community-dwelling older
      adults in Quebec who participated in the Canadian Study of Health and Aging
      (CSHA1). MEASUREMENTS: Patient characteristics were obtained from the CSHA1
      database. These were linked to provincial health insurance data to ascertain
      benzodiazepine use and prescriber characteristics. MAIN OUTCOME MEASURE: Use of
      benzodiazepines for at least 135 of the first 180 days following initiation of
      use. RESULTS: Twelve-month prevalence of long-term continuous use, standardized
      by age and gender to the Quebec population, was 19.8%. Twelve-month cumulative
      incidence of long-term continuous use was 1.9%. Older patients were more likely
      to proceed to long-term continuous use. CONCLUSIONS: Risk of long-term continuous
      use of benzodiazepines seems to increase with age. This association was found to
      be independent of gender, health status, anxiety, cognitive status,
      benzodiazepine type, and physician characteristics.

PMID- 10894321
TI  - Effect of enalapril and nifedipine on orthostatic hypotension in older
      hypertensive patients.
AB  - OBJECTIVE: To compare the effect of enalapril with long-acting nifedipine on
      orthostatic hypotension in older patients. DESIGN: A prospective, double blinded,
      cross-over study. SETTING: The outpatient clinic of a university hospital.
      PARTICIPANTS: Thirty-nine patients aged 65 years or older with systolic blood
      pressure (SBP) of 140-190 mm Hg and diastolic blood pressure (DBP) of 90-110 mm
      Hg. INTERVENTION: Enalapril 5-20 mg od or nifedipine 30-90 mg od for 8 weeks,
      followed by 4 weeks washout and cross-over for a second 8-week period.
      MEASUREMENTS: Supine and standing 0-, 1-, and 5-minutes blood pressure was
      recorded before and at the end of each treatment period. RESULTS: At baseline,
      SBP was 158.8 +/- 8.7 mm Hg, and DBP was 97.1 +/- 5.9 mm Hg. There was a decline
      in SBP of 6.1 +/- 2.7 mm Hg and 8.4 +/- 4.1 mm Hg after 1 and 5 minutes of
      standing, respectively. Both agents caused a significant decline in supine blood
      pressure. Enalapril: supine SBP 158.8 +/- 8.7 to 143 +/- 7.3 mm Hg; supine DBP
      97.1 +/- 5.9 to 85.1 +/- 5.1 mm Hg (P = .0001). The drop in SBP after standing
      for 5 minutes was only 2.4 +/- 1.6 mm Hg with no change in diastolic values. A >
      or = 10 mm Hg drop in SBP was observed in only three patients, and no patient
      experienced a decline of 20 mm Hg or more. Nifedipine: supine SBP: 160.3 +/- 9 to
      145.3 +/- 8.1 mm Hg; supine DBP: 96.3 +/- 5.7 to 86.3 +/- 5.8 (P = .0001).
      Nifedipine induced an orthostatic decline in SBP values; there was an 8.7 +/- 4.8
      mm Hg difference between supine and 5 minutes standing values (P = .0005) without
      change in diastolic values. An orthostatic decline in SBP of > or = 10 mm Hg
      occurred in 13 patients, and there was a drop of > or = 20 mm Hg in six patients.
      The cross-over of enalapril and nifedipine reproduced the hypotensive effect and
      reversed the postural effect. (P = .0002 nifedipine vs enalapril) CONCLUSIONS:
      Enalapril and nifedipine were equipotent in reducing supine blood pressure
      levels. Enalapril also reduced the number of orthostatic episodes significantly,
      whereas nifedipine aggravated this phenomenon.

PMID- 10894323
TI  - Mammography use among women as a function of age and patient involvement in
      decision-making.
AB  - OBJECTIVE: To assess the extent to which self-reported patient involvement in
      decision-making for initiation of mammography differs with age. DESIGN: Data from
      the 1992 National Health Interview Survey (NHIS) Cancer Control Supplement were
      evaluated. Prevalences were weighted and variances were adjusted using SUDAAN
      software to account for the complex, multistage sampling probability design of
      the NHIS. Logistic regression was used to evaluate the relative likelihood of
      self-reported involvement in the decision to have a mammogram within the
      preceding year as a function of age and other covariates. PARTICIPANTS:
      Mammography use was assessed among 3,863 NHIS female respondents 40 years of age
      or older. The analysis of decision-making was restricted to the subgroup of 1,064
      women who reported a screening mammogram within the preceding year and who
      provided information on the other relevant variables. MEASUREMENTS AND MAIN
      RESULTS: The probability of reported mammography use within the preceding year
      declines among older groups of interviewees. Among women with a mammogram in the
      preceding year, the weighted percentage of women reporting active involvement in
      the decision (patient decision or decided jointly with a physician) declines from
      51% among women 40 to 45 years of age to 19% among those aged 75 years or older.
      The adjusted odds ratio comparing the likelihood of participating in the decision
      to have a mammogram for the oldest women, compared with the youngest, was 0.31
      (95% confidence interval 0.15 to 0.61). CONCLUSIONS: Older women are
      substantially less likely than younger women to report active involvement in the
      mammography decision-making process. Increased use of screening mammography among
      older women will require greater promotion by physicians. Other interventions,
      such as directed educational efforts, may also be needed to increase mammography
      demand among older women.

PMID- 10894324
TI  - Pharmacotherapy of lower limb diabetic ulcers.
AB  - OBJECTIVE: To discuss the pathophysiology, microbiology, and pharmacotherapy of
      lower extremity (LE) diabetic ulcers. DATA SOURCES: A MEDLINE search from 1966 to
      April 1999 was conducted. The search was limited to humans and English-language
      journals. Key search words included "diabetic ulcer," "fluoroquinolones," "beta
      lactam," "hyperbaric oxygen," "diabetes mellitus," "diabetic foot," and "growth
      factor." STUDY SELECTION: Randomized and nonrandomized studies were selected for
      review. Results of randomized, placebo-controlled studies were emphasized more
      than nonrandomized results. DATA SYNTHESIS: LE ulcers are a common cause of
      hospitalization, and cause significant morbidity and mortality. Staphylococcus
      aureus is the most common pathogen in non-limb-threatening infections; Gram
      negative bacteria and anaerobes are most prevalent in limb-threatening and life
      threatening infections. Oral antibiotic therapy may be used in non-limb
      threatening infections, if adequate response is achieved in 24-48 hours;
      otherwise, intravenous antibiotics should be started. Intravenous antibiotics
      should be the initial therapy for limb-threatening or life- threatening ulcers.
      Antimicrobial therapy of at least 10-14 days has been effective in treating LE
      ulcers in the absence of osteomyelitis. Growth factors offer another treatment
      alternative, although only becaplermin is currently approved for diabetic ulcers.
      CONCLUSION: Antibiotic therapy has been effective for the treatment of LE
      diabetic ulcers. However, further studies are required to identify optimal
      antibiotics and dosage regimens. Growth factors may have a role but additional
      research is needed to determine when best to initiate this therapy.

PMID- 10894325
TI  - Implementing the second generation social health maintenance organization.
AB  - BACKGROUND: In 1996 the Health Care Financing Administration implemented a second
      generation of the Social HMO demonstration. This model retained the chronic care
      benefits of the original Social HMOs while attempting to develop a geriatric
      service model integrated into primary care and a screening and assessment process
      focused directly on healthcare risk factors. Other refinements included risk
      adjusted capitation payment, broadened eligibility for expanded care benefits,
      low co-payments for these benefits, and no caps on the expanded care benefits
      expenditures. OBJECTIVES: The geriatric approach is designed to facilitate
      integration among providers and levels of care. This includes timely application
      of primary care monitoring and treatment to reduce illness and disability as well
      as a geriatric education and consultation program to provide specialty support
      for complex cases. Care management is designed for those requiring home-based
      care, those discharged from hospitals or nursing homes, and those having
      difficulty with treatment regimens. DESIGN: A case study of the Social HMO
      implementation through the Fall of 1999. SETTING: Health Plan of Nevada (HPN),
      with locations in Las Vegas, Reno, and surrounding areas. PARTICIPANTS: More than
      25,000 Medicare beneficiaries participated during the study period. MEASUREMENTS:
      Administrative reports, charts, and interviews with administrators and
      clinicians. RESULTS: Within 12 months of operation under this authority, HPN
      succeeded in putting in place most of the components of the planned geriatric
      approach: a screening program to identify patients "at risk" for high service
      costs and disability and timely application of primary care treatment to reduce
      illness and disability. Geriatric education and a consultation program for
      complex cases were available, but full implementation was delayed until the plan
      was able to hire a full time geriatrician. CONCLUSIONS: Health Plan of Nevada's
      Social HMO program reflects current perspectives on how to integrate chronic care
      into an HMO. The accomplishments affirm that the provision of risk-adjusted
      reimbursement, along with the 5 % supplement to the normal Medicare capitation
      payment, are sufficient incentives for a health plan to restructure itself so
      that it places a priority on retaining and serving populations at risk for high
      expenditures.

PMID- 10894326
TI  - So you think you want to lead an academic geriatric program?

PMID- 10894327
TI  - Breast cancer screening in older women. American Geriatrics Society Clinical
      Practice Committee.

PMID- 10894328
TI  - Ambulatory geriatric clinical care and services. American Geriatric Society
      Health Care Systems and Clinical Practice Committees.

PMID- 10894329
TI  - Urge incontinence and the risk of falling in older women.

PMID- 10894330
TI  - The quality of managed care is strained.

PMID- 10894332
TI  - Encouraging older patients to exercise.

PMID- 10894331
TI  - Closing the gap--provider and researcher responsibility.

PMID- 10894333
TI  - A pilot program of community-based screening for memory impairment.

PMID- 10894334
TI  - Excessive sweepstakes participation by persons with dementia.

PMID- 10894335
TI  - Inappropriate use of therapeutic diets in the nursing home.

PMID- 10894336
TI  - Safety of once-daily aminoglycosides in older people.

PMID- 10894337
TI  - Advance research directives: implementation issues.

PMID- 10894338
TI  - IGF-1 and ischemic heart disease in older people.

PMID- 10894339
TI  - Medical training in crisis.

PMID- 10894340
TI  - Cannabis use and dependence in a New Zealand birth cohort.
AB  - AIM: To describe the development of cannabis use in a birth cohort studied to the
      age of 21 years. METHODS: The data were gathered during the Christchurch Health
      and Development Study. In this study a cohort of 1265 children born in the
      Christchurch urban region in mid 1997 has been studied to the age of 21 years.
      Information was gathered on patterns of cannabis use and dependence during the
      period from fifteen to 21 years. RESULTS: By age 21 years, 69% of the cohort had
      used cannabis. The extent varied widely with 24% reporting use of cannabis on
      less than ten occasions while 5% reported use on over 400 occasions. Over 9% of
      the cohort met DSM-IV criteria for cannabis dependence by the age of 21 years.
      Cannabis use and dependence were higher in males and in Maori. Key predictors
      were gender and measures of adolescent risk taking behaviours including cigarette
      smoking, adolescent conduct problems, affiliations with delinquent peers and
      novelty seeking. CONCLUSIONS: Levels of cannabis use in this cohort reached a
      point where it was considered 'normal'. For the majority of users cannabis use
      did not lead to problems of dependence. Nonetheless, nearly 10% of the cohort
      showed clear symptoms of cannabis dependence by the age of 21 years, especially
      males who were prone to other forms of risk taking behaviours.

PMID- 10894341
TI  - An audit of phase II cardiac rehabilitation at Auckland hospital.
AB  - AIM: To audit Phase II cardiac rehabilitation services available to patients
      admitted to Auckland Hospital in order to assess patient uptake and to identify
      problems with patient recruitment to the service. METHODS: We performed a
      retrospective review from 1/8/ 97 to 30/9/97 of all patients admitted to the
      coronary care/ cardiology departments in Auckland Hospital. RESULTS: There were
      289 patient admissions in this two month period, of which 22 (8%) were
      readmissions. 154 (54%) were admissions with provisional diagnoses of chest pain,
      of whom eight were readmissions. A total of 113 (39%) patients were felt to be
      suitable for the rehabilitation programme, of whom 50 (44%) attended one or more
      sessions and 22 (19%) completed the six week programme. 63 (56%) of the eligible
      patients did not attend any session. Reasons for non-attendance included the
      distance to be travelled, availability of transport and problems associated with
      taking time off work. A major finding of the audit was that the systems currently
      in place to follow patients are inadequate to allow formal audit and evaluation
      of the rehabilitation service. CONCLUSIONS: Although a reasonable rehabilitation
      service exists for Auckland Hospital patients, less than half of suitable
      patients attend a single session. There is a need for better collection and
      recording of patient data in order to facilitate the development of evaluation
      and audit tools.

PMID- 10894342
TI  - Severe community acquired pneumonia: a one-year analysis in a tertiary referral
      intensive care unit.
AB  - AIMS: To define outcomes, characteristics, microbiology and salient prognostic
      factors of patients admitted to our intensive care unit (ICU) with severe
      community acquired pneumonia, over a one year period. METHODS: All adult patients
      with severe community acquired pneumonia admitted between July 1997 and July 1998
      were studied. Data were extracted by retrospective chart review. Variables
      assessed included underlying conditions and baseline physical parameters.
      Evolutionary variables eg, septic shock and laboratory data including
      microbiology and arterial blood gas determinants were also assessed. Prognostic
      factors were determined by comparison of the above variables between survivors
      and non-survivors. The prognostic value of the British Thoracic Society
      discriminant 'rule one' was assessed. Results. 32 patients were assessed. ICU
      mortality was 31%. 84% of patients had co-morbidity. The average age was 58.5 (SD
      17.4) years and the average APACHE 11 score was 20.37 (SD 9.12). A
      microbiological diagnosis was made in 40%. Mortality was not increased in those
      in whom a bacterial diagnosis was not made. Commonest pathogens isolated were
      Streptococcus pneumoniae (46%), gram negative organisms (29%) and Staphylococcus
      aureus (23%). Prognostic factors on and during ICU admission were the need for
      mechanical ventilation (p=0.0003), septic shock (p=0.02), inotrope requirement
      (p=0.003), low serum albumin (p=0.041), base deficit (p=0.04), INR (p=0.02) and
      inspired oxygen concentration (p=0.003). On initial admission to hospital the
      presence of bilateral pneumonia was the only variable correlated with outcome
      (p=0.01). The British Thoracic Society 'rule one' did not correlate with death
      either on admission to hospital or ICU. CONCLUSIONS: Severe community acquired
      pneumonia carries a high mortality despite ICU management. Bacterial diagnostic
      rate was low but made no difference to mortality. Streptococcus pneumoniae was
      the commonest causative pathogen. The development of septic shock, requirement
      for mechanical ventilation and bilateral disease are important adverse prognostic
      indicators.

PMID- 10894343
TI  - Skin and soft tissue infections.

PMID- 10894344
TI  - Guidelines for the management of women with abnormal cervical smears 1998.
AB  - Four important changes have been introduced in the revised guidelines for the
      management of women with abnormal cervical smears, 1998. 1. For the purposes of
      management, atypical squamous cells of undetermined significance (ASCUS) and
      atypical glandular cells of undetermined significance (AGUS) have been included
      with low grade squamous intraepithelial lesions (LSIL/CIN1/HPV) except where the
      smear raises the possibility of a high grade squamous intraepthelial lesion
      (HSIL) or favours glandular dysplasia. 2. Women with low grade cytological and
      histological intraepithelial abnormalities will, after initial follow-up, revert
      to three yearly screening. 3. Requirements for those practising colposcopy have
      been defined. 4. A formal review of all cases of invasive cervical cancer is
      advocated.

PMID- 10894345
TI  - Management of hepatocellular carcinoma in New Zealand.

PMID- 10894346
TI  - New Zealand's ageing drivers.

PMID- 10894347
TI  - New Zealand's ageing drivers.

PMID- 10894348
TI  - Misuse of the Accident Insurance Act (1998) procedures to infringe patient
      rights.

PMID- 10894349
TI  - Progress in graft-versus-host disease.

PMID- 10894350
TI  - Autologous graft-versus-host disease.

PMID- 10894351
TI  - Pathogenesis of acute graft-versus-host disease: cytokines and cellular
      effectors.
AB  - The pathogenesis of acute graft versus host disease (GVHD) is multistep process.
      This review considers acute GVHD in three sequential steps: conditioning regimen,
      donor T cell activation, and effector mechanisms. In step one, the conditioning
      regimen simultaneously damages and activates host tissues, amplifying antigen
      presentation to allogeneic donor T cells. In step two, donor T cells, activated
      by host alloantigens, proliferate and secrete a variety of cytokines. Type 1
      cytokines (interleukin-2 and interferon-y) are critical for acute GVHD, but
      several regulatory mechanisms of tissue damage include inflammatory cytokines and
      cytolytic cellular effectors. The gastrointestinal (GI) tract is a principal
      target organ because damage to the GI mucosa can release inflammatory mediators
      such as endotoxin that amplify systemic disease. The inflammatory processes of
      acute GVHD can be considered as a distortion of the cellular responses to viral
      and bacterial infections. Cell-mediated toxicity is critical to other GVHD target
      organs, particularly the liver, where Fas-mediated injury predominates. The
      cytolytic pathways (e.g., perforin) clearly intensify acute GVHD, although they
      are not necessary for systemic disease in several model systems. Many of these
      insights come from animal models using mutant mouse strains that can clarify the
      role of individual proteins or cell types in the disease process. These insights
      should allow the testing of new classes of drugs and inhibitors in clinical bone
      marrow transplantation.

PMID- 10894352
TI  - Role of natural killer cells in the development of graft-versus-host disease.

PMID- 10894353
TI  - Drug therapy for acute graft-versus-host disease prophylaxis.
AB  - The mechanisms of many immunosuppressive drugs have been defined, allowing for a
      rational approach to the use of these agents in GVHD prophylaxis. In addition to
      standard drugs such as methotrexate, cyclosporine, tacrolimus, and
      glucocorticoids, new agents-mycophenolate mofetil, tresperimus, rapamycin,
      basiliximab, and daclizumab-are now part of the immunosuppressive armamentarium.
      Improved understanding of tolerance has resulted in new approaches to prevention
      of GVHD. Anti-CD40L, CTLA-4-Ig, tresperimus, and rapamycin are agents that are
      being explored in this area and have shown impressive results in animal models.
      Currently, the standard therapy for acute GVHD prophylaxis in matched sibling
      transplants remains cyclosporine and methotrexate. Lower dose methotrexate,
      particularly in combination with tacrolimus, has shown good results in single arm
      studies with low toxicity, but this has not been tested in a randomized study.
      For unrelated donor transplants there is less GVHD when tacrolimus, rather than
      cyclosporine, is combined with methotrexate; there seems little reason to use
      cyclosporine in this setting. GVHD is still the major barrier to more widespread
      use of unrelated donor transplants and improved regimens are needed. In vivo T
      cell depletion using Campath-1 or ATG is being used in high-risk patients. Data
      on its efficacy are so far anecdotal. Due to the variation in grading of GVHD
      between centers, randomized studies are needed to quantify the relative merits of
      different regimens, and participation in such studies is encouraged.

PMID- 10894354
TI  - Evolving strategies to address adverse transplant outcomes associated with T cell
      depletion.
AB  - Graft-versus-host disease (GVHD) is the major complication of allogeneic bone
      marrow transplantation (BMT). The most effective strategy to reduce GVHD has been
      T cell depletion (TCD) of the donor marrow graft. Although TCD has reduced both
      the incidence and severity of GVHD, it has been associated with an increased rate
      of graft rejection and an impairment in immune reconstitution after transplant.
      Relapse rates in selected hematologic malignancies have also been higher after
      TCD allogeneic BMT. Over the past several years, a number of clinical strategies
      have been developed in an effort to reduce adverse transplant outcomes associated
      with TCD. This review examines some of the strategies designed to promote
      alloengraftment, prevent relapse, and enhance immune reconstitution after TCD.

PMID- 10894355
TI  - Chronic graft-versus-host disease.

PMID- 10894356
TI  - The benefits of an alloresponse: graft-versus-tumor.

PMID- 10894357
TI  - Toward amplification of a graft-versus-leukemia effect while minimizing graft
      versus-host disease.

PMID- 10894358
TI  - Treatment of steroid-resistant acute graft-versus-host disease with rabbit
      antithymocyte globulin.
AB  - Acute graft-versus-host disease (A-GVHD) is a life-threatening complication of
      allogeneic stem cell transplantation (SCT), and primary therapy consists of high
      dose corticosteroids. Patients who fail to respond adequately to corticosteroids
      require salvage treatment, with anti-T cell antibodies being the most commonly
      utilized group of agents. We report our institution's experience treating steroid
      resistant GVHD in 36 adult patients (median age 39 years, range 24-55) with a
      rabbit antithymocyte globulin product (thymoglobulin). Eleven patients had
      undergone sibling SCT (10 histocompatible, 1 one-antigen mismatched) and 25
      patients had received unrelated donor bone marrow (17 matched, 8 one-antigen
      mismatched); 32 patients (89%) had grade III or IV A-GVHD. Thymoglobulin was
      administered in two different regimens; group 1 patients (n = 13) received 2.5
      mg/kg/day x 4-6 consecutive days with maintenance of all other
      immunosuppressives. Group 2 patients (n = 21) were given the same dose of
      thymoglobulin on days 1, 3, 5, and 7 with discontinuation of cyclosporine for 14
      days, during which the corticosteroid dose was held at 2-3 mg/kg/day. Two
      patients had severe adverse reactions to thymoglobulin (hypoxemia and
      hypotension) and could not complete treatment, however, in the other patients,
      aside from transient leukopenia (25%) and and hepatic dysfunction (25%), the
      antibody preparation was well tolerated. Of the 34 evaluable patients, 13
      patients had a complete response (38%) and 7 patients (21%) had a partial
      response, for an overall response rate of 59%. Response rate was higher in group
      1 patients (77%) compared to group 2 patients (48%), (p = 0.15); skin GVHD was
      more responsive (96% of patients) than gut GVHD (46% of patients) or hepatic GHVD
      (36% of patients). Opportunistic infections were a significant complication, with
      11 patients developing systemic fungal infections and 9 patients serious viral
      infections; there were seven episodes of bacteremia following thymoglobulin
      treatment and one fatal protozoal infection. There were 9 patients (25%) who
      developed post-SCT lymphoproliferative disorder (PTLD) and 4 patients who had a
      relapse of underlying primary malignancy; none of these patients survived. Of the
      36 patients entered on the study, only 2 patients (6%) survive, at 15+ and 34+
      months post-unrelated donor SCT. Although thymoglobulin is associated with an
      impressive response rate when administered for advanced steroid-resistant GVHD,
      long-term survival is uncommon, even in responders, primarily due to the high
      risk of developing either an opportunistic infection or a PTLD.

PMID- 10894359
TI  - Autologous graft-versus-host disease after CD34+-purified autologous peripheral
      blood progenitor cell transplantation.
AB  - Autologous graft-versus-host disease (GVHD) has been frequently reported after
      cyclosporine A (CsA) administration in the autologous setting. This complication
      is related to the disruption of self-tolerance mechanisms induced by CsA and may
      exert an antitumor effect. We report the spontaneous occurrence of autologous
      GVHD after CD34+-purified peripheral blood progenitor cell transplantation
      (PBPCT) in 5 out of 24 consecutive patients (20.8%). The syndrome was
      characterized by skin rash (5/5), pruritus (5/5), eosinophilia (5/5), and fever
      (2/5) occurring at a median of 37 days (range 22-60) after transplantation.
      Diagnosis was confirmed by skin biopsy in all patients. The syndrome was self
      limiting, lasted a median of 25 days, and did not require treatment. The rate of
      autologous GVHD was high after CD34+-purified autologous PBPCT. In fact, no
      autologous GVHD was documented in an historical control of 100 consecutive
      patients submitted to unmanipulated PBPCT at the same institution. The
      manipulation of the graft by the purging procedure causes a profound T lymphocyte
      depletion, thus possibly perturbing the equilibrium between autoregulatory cells
      and autocytotoxic T cells. These observations add new interest to the antitumor
      efficacy of autologous GVHD and suggest new questions regarding the role of
      transplantation for autoimmune diseases.

PMID- 10894360
TI  - Upregulation of interleukin-10 and inhibition of alloantigen responses by
      transferrin and transferrin-derived glycans.
AB  - Previous studies have shown that critically timed administration of transferrin
      (Tf) facilitates induction of immunologic unresponsiveness. Here, we determined
      in mixed leukocyte culture (MLC) and in concanavalin A (ConA)-driven cultures the
      effect of exogenous Tf and Tf-derived glycans (Tf-Gly) on lymphocyte
      proliferation. In cultures of human blood lymphocytes, Tf inhibited selectively
      alloantigen-driven proliferation in MLC, but not ConA-stimulated lymphocyte
      proliferation. Deglycosylation of Tf abrogated the inhibitory effect of Tf on
      alloantigen-induced lymphocyte proliferation, and, consistent with a role for
      glycans, an effect qualitatively and quantitatively similar to Tf was exerted by
      purified Tf-Gly. Glycans isolated from other proteins, for example,
      immunoglobulin G (IgG) or fibrinogen, failed to inhibit alloantigen-induced
      proliferation selectively. Rather, they suppressed lymphocyte proliferation in a
      non-specific manner. Determination of cytokines in MLC supernatant showed a
      downregulation of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF
      alpha), IL-2, and IL-12 (p40), along with an upregulation of IL-10, a pattern
      entirely consistent with the observed effects of Tf and Tf-Gly on alloantigen
      induced lymphocyte proliferation. The effect of Tf on MLC was directly IL-10
      dependent. IL-10 levels were inversely correlated with lymphocyte proliferation
      and CD86 expression. Neutralization of IL-10 by anti-IL-10 monoclonal antibody
      (mAb) blocked the effect of Tf. The MLC-modulating effect of Tf (or Tf-Gly) was
      not dependent upon the Tf receptor CD71 but appeared to be mediated by a Gly
      responsive receptor. These data suggest a role of Tf, and, in particular, Tf-Gly,
      in allo-interactions that is independent from the role of Tf in iron metabolism,
      and appears to involve co-stimulatory signals.

PMID- 10894361
TI  - Soluble interleukin-2 receptor concentration as a biochemical indicator for acute
      graft-versus-host disease after allogeneic bone marrow transplantation.
AB  - When interleukin-2 (IL-2) binds to the IL-2 receptor (IL2-R) on activated T
      cells, a soluble portion of the receptor (sIL2-R) is released. After allogeneic
      bone marrow transplantation (BMT), the serum concentration of sIL2-R may,
      therefore, be a useful surrogate marker for T cell activation that results in
      acute graft-versus-host disease (aGVHD). To determine if the sIL2-R concentration
      is a useful marker to help establish a diagnosis of aGVHD, serial sIL2-R
      concentrations were measured weekly for 4 weeks in 43 patients after allogeneic
      BMT. Grafts were from HLA-matched siblings (n = 33), 5/6 HLA-matched siblings (n
      = 3) or matched unrelated donors (n = 7). GVHD prophylaxis included cyclosporine
      A (CSA)/methotrexate (MTX) (n = 25), solumedrol/CSA (n = 15), or T cell depletion
      (n = 3). Twenty-three patients developed aGVHD (Grade I, 7; Grade II, 12; Grade
      III, 4) a median of 28 days after transplant. There was a significant association
      between a clinical diagnosis of aGVHD and an increase in the sIL2-R concentration
      (p < 0.001). The mean percent increase (+/-SE) over baseline for patients with a
      clinical diagnosis of aGVHD was 294% (+/-57%) by week 2 (n = 12), 431% (+/-116%)
      by week 3 (n = 14), and 650% (+/-315%) by week 4 (n = 9) after BMT. For each 100%
      increase over baseline, the likelihood of having aGVHD increased by 18%. Six of
      20 patients without aGVHD became critically ill and exhibited marked increases in
      sIL2-R concentrations, similar to patients with a clinical diagnosis of aGVHD who
      never became critically ill. Fourteen patients without aGVHD who did not become
      critically ill exhibited negligible increases of sIL2-R in 2- to 4-week period
      after BMT. These data suggest that serial measurements sIL2-R concentration are
      helpful in establishing the diagnosis of aGVHD, but are not useful in the most
      acutely ill patients.

PMID- 10894362
TI  - Boswellic acids inhibit glioma growth: a new treatment option?
AB  - Conventional malignant glioma therapy (surgery, radiation therapy and
      chemotherapy) does not yield satisfying results. The prognosis of the glioma
      patient depends more on the histological grading of the tumor and patient's age
      than on the therapy. Especially the adjuvant chemotherapy failed to date to
      influence survival time in glioma patients significantly. To improve results in
      malignant glioma therapy additional therapeutic regimes are necessary. In an
      earlier study we were able to show a significant reduction on perifocal edema by
      an extract from gum resin (EGR) accompanied with a clinical improvement in
      patients with malignant glioma. Also a decrease of urinary LTE4-excretion as a
      metabolite of leukotriene synthesis in brain tumors was observed. Furthermore we
      had found a proliferation inhibiting activity of the extract form EGR, the
      boswellic acids in cell cultures. The purpose of this experimental study was to
      elucidate the effects of the boswellic acids, which are constituents of an
      extract from gum resin on tumor growth in vivo. Female wistar rats weighing 200
      250 g were treated with the drug 14 days after inoculation of C6 tumor cells into
      their right caudate nucleus and randomization into 4 groups. The treatment groups
      received different dosages and were compared to a control group without any
      additional treatment. Survival time of the rats in the highest dosage group (3 x
      240 mg/kg body weight) was more than twice as long as in the control group (P <
      0.05). In a second experiment the inhibition of tumor cell proliferation was
      examined. The C6 tumor cells were implanted into the caudate nucleus. Drug
      treatment was started immediately after implantation and stopped after 14 days.
      The animals were sacrificed and the brains were examined microscopically.
      Comparing low and high dosage of EGR treatment a significant difference in tumor
      volume was detected (P < 0.05). The proportion of apoptotic tumor cells in
      animals with high dose treatment was significantly larger than in the low dose
      (treatment) group (P < 0.05). These data demonstrate an influence of EGR in rat
      glioma growth and might represent a new therapeutic option on glioma treatment in
      man in future. Further experimental work on human gliomas is needed to
      definitively answer this question.

PMID- 10894363
TI  - The expression and activation of matrix metalloproteinase-2 in rat brain after
      implantation of C6 rat glioma cells.
AB  - It has been reported that matrix metalloproteinases (MMPs) are highly expressed
      in malignant glioma cells and that this increased expression may facilitate the
      invasiveness of tumor cells. The authors investigated the expression and
      enzymatic activity of MMPs in rat brain during the growth of malignant gliomas at
      different time intervals. C6 rat glioma cells were unilaterally implanted into
      rat cerebral hemispheres. After 7 or 14 days, these brain tissues were prepared
      for SDS-PAGE zymography, Western blotting, immunohistochemistry, and in situ
      zymography. SDS-PAGE zymography and Western blotting revealed that the expression
      of proMMP-2 in rat brains with C6 glioma cells was significantly higher than that
      in normal or the sham-operated rat brains, and that the activated form of MMP-2
      was detected only in the former but not in the latter. On immunohistochemistry,
      C6 glioma cells presenting invasive growth into the rat brain parenchyma and
      vessels demonstrated MMP-2 immunoreactivity. On in situ zymography, foci of
      invasive C6 glioma cells in rat brain tissue showed gelatinolytic activity. These
      results suggest that expression and activation of MMP-2 may be one of the crucial
      steps for glioma cell invasion into the brain parenchyma in vivo.

PMID- 10894364
TI  - Up-regulation of urokinase-type plasminogen activator and its receptor correlates
      with enhanced invasion activity of human glioma cells mediated by transforming
      growth factor-alpha or basic fibroblast growth factor.
AB  - Glioblastoma multiforme is a highly malignant tumor that is extremely refractory
      to therapy. One reason is its highly invasive nature into brain tissue.
      Metalloproteinases and their inhibitors, plasminogen activators (PA) and their
      inhibitors and cathepsins are thought to be involved in invasion by tumor cells.
      In this study, we determined if the urokinase-type plasminogen activator (uPA)
      and/or the urokinase-type plasminogen activator receptor (uPAR) were responsible
      for the invasion activity of a human glioma cell line. We determined the invasion
      activity of a human glioma U251 cell line using an in vitro invasion assay
      system. A 2.4- to 5.8-fold increase in invasion activity was observed in the
      presence of basic fibroblast growth factor (bFGF) or transforming growth factor
      (TGF)-alpha. Northern blot analysis showed that bFCF and TGF-alpha treatment was
      associated with increases in cellular mRNA levels of uPA and uPAR. Zymographic
      activity correlated to mRNA levels of uPA and uPAR. Addition of an anti-uPAR
      monoclonal antibody significantly inhibited the invasion activity induced by bFGF
      and TGF-alpha. Irsogladine, an inhibitor of uPA synthesis, also blocked the
      invasion activity. These observations suggest that uPA and its receptor have a
      role in the invasion process of human gliomas.

PMID- 10894365
TI  - Selenium causes growth inhibition and apoptosis in human brain tumor cell lines.
AB  - We examined the effect of the trace element selenium on human glioma cell lines:
      T98G, U373MG, and U87MG, in addition to dermal fibroblast cells. Cultures were
      incubated with sodium selenite, and the following parameters were studied: cell
      growth, mitochondrial function, and ultrastructure. Cell growth was assayed by
      counting the number of viable cells after treatment with selenium. Mitochondrial
      function was analyzed using the MTT (tetrazolium salt reduction) assay. Apoptosis
      was determined by evaluating nuclear chromatin condensation by electron
      microscopy. The results indicated that selenium had a significant inhibitory
      effect on the growth of the tumor cells but had little effect upon dermal
      fibroblasts which had been passaged numerous times. Selenium also induced
      mitochondrial damage as shown by MTT assay in two brain tumor cell lines and in
      minimally passaged fibroblasts, but it had little effect upon the high-passage
      fibroblasts. Ultrastructurally, mitochondria had electron-dense inclusions
      resulting from selenium treatment. High rates of apoptosis were induced by
      selenium in the tumor cell lines and in the minimally passaged fibroblasts,
      whereas the fibroblasts with a high number of passages had some resistance to
      selenium treatment. This study correlates the adverse effects of selenium on
      mitochondrial function, inhibition of cell growth, and apoptosis and shows that
      selenium similarly affects three different brain tumor cell lines and minimally
      passaged fibroblasts. Further, the results with fibroblasts show that some types
      of cells after repeated passages can develop resistance to selenium damage.

PMID- 10894366
TI  - Human malignant glioma therapy using anti-alpha(v)beta3 integrin agents.
AB  - Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in
      adults and is invariably fatal. We have investigated the effect of cyclo-(Arg-Gly
      Asp-D-Phe-Val) (cRGDfV) peptide on survival of human malignant glioma cells in
      vitro and in vivo. Immunofluorescent analyses revealed the presence of
      alpha(v)beta3 integrin on U-87MG and U-373MG cells, but minimal expression on U
      251MG cells. Treatment of U-87MG and U-373MG cells in vitro with cRGDfV (20
      microg/ml), but not the linear peptide, resulted in the appearance of rounded and
      loosely attached cells with subsequent cell death. By comparison, neither this
      cyclic peptide nor its linear homolog had any significant effect on growth and
      morphology of U-251MG cells. The death of cRGDfV-treated (20 microg/ml) glioma
      cells was blocked by pretreatment (10 microM) of cells with DEVD-FMK and LEHD
      FMK, inhibitors of caspase-3 and caspase-9, respectively. Moreover, when glioma
      cells grown as spheroids were treated with cRGDfV (50 microg/ml), spheroid
      formation was markedly reduced. Further, treatment of intracranial U-87MG tumors
      in scid mice with cyclic peptide significantly (p < 0.001) prolonged their
      survival. These results indicated (i) that cRGDfV induced apoptosis of human
      glioma cells by binding alpha(v)beta3 integrin expressed on their cell surfaces
      and (ii) that cRGDfV may be an effective and non-toxic direct anti-tumor therapy
      for alpha(v)beta3-expressing GBMs.

PMID- 10894367
TI  - Ultrastructural changes of the vascular endothelium after intra-arterial
      administration of tumor necrosis factor-alpha (TNFalpha) in rat gliomas.
AB  - The ensuing ultrastructural changes in tumor vascular endothelial cells following
      intra-arterial administration of tumor necrosis factor-alpha (TNFalpha) were
      studied in an experimental rat glioma model. C6 glioma cells were implanted in
      Wistar rats and then after 14 days, 5 x 10(3) U of human natural-type TNFalpha
      (1.7 x 10(5) U/m2) was administered through the carotid artery. The animals were
      sacrificed at 3 or 24 h after TNFalpha treatment. A detailed examination with
      transmission electron microscope revealed swelling of the tumor vascular
      endothelial cell nuclei and mitochondria with matrix densities at 3 h. At 24 h,
      these cells demonstrated the presence of high amplitude mitochondrial swelling or
      the violent blebbing characteristic of damaged mitochondria; the cytoplasm was
      swollen enormously and there were dissolution of cytoplasmic organelles and
      rupture of the plasma membrane. The observed findings were typical of cell
      necrosis and confirms yet another mechanism by which TNFalpha exerts its anti
      tumor effects, that is, necrotizing effects on tumor vascular endothelium. The
      information appears to be important in the context of clinical application of
      intra-arterial TNFalpha in the treatment of malignant gliomas.

PMID- 10894368
TI  - Evaluation of pre-radiotherapy cyclophosphamide in patients with newly diagnosed
      glioblastoma multiforme. Writing Committee for The Brain Tumor Center at Duke.
AB  - Cyclophosphamide is an alkylating agent that has shown activity in the treatment
      of pediatric brain tumors, including high-grade gliomas. This study was designed
      to evaluate the response of patients with newly diagnosed glioblastoma multiforme
      to pre-radiotherapy cyclophosphamide. Fourteen patients with glioblastoma
      multiforme were treated with high-dose cyclophosphamide (2 g/m2/day for 2 doses
      every 28 days) followed by either sargramostim or filgrastin. Sargramostim was
      given 250 microg/m2 subcutaneously twice a day continuing through the leukocyte
      nadir until the absolute neutrophil count was more than 1000 cells/microl for 2
      consecutive days. The filgrastin dose was 10 microg/kg given subcutaneously once
      daily until the post nadir absolute neutrophil count was > or = 10,000
      cells/microl. A total of 46 courses was given. Four patients received a total of
      3 courses, 7 patients completed 4 courses and 3 patients received 2 courses.
      Three patients demonstrated complete response; 3 stable disease; and 8
      progressive disease. The most common toxicity was hematologic, requiring platelet
      and packed red blood cell transfusions, with 13 admissions for neutropenia with
      fever. There were no deaths related to infection or bleeding. These results
      suggest that high-dose cyclophosphamide has modest activity with acceptable
      toxicity against newly diagnosed glioblastoma multiforme.

PMID- 10894371
TI  - Revision surgery after failed subacromial decompression.
AB  - The purpose of this study was to assess the results of revision subacromial
      decompression and identify clinical and psychological factors that influence its
      outcome. Thirty-five patients with intact rotator cuffs who underwent surgery for
      recurrent stage II impingement were studied at a mean follow-up time of 43 months
      post-surgery. Twenty-seven patients were satisfied with their surgery. The UCLA
      Scoring System rated 18 of 35 with good/excellent results and 17 of 35 poor/fair
      results, 22 patients had worker's compensation injuries, which correlated with
      poor outcome (P=0.0067). Patients with concomitant brachial plexopathy and/or
      compressive neuropathies were associated with unsatisfactory results (P=0.02).

PMID- 10894370
TI  - 201Thallium SPECT and 1H-MRS compared with MRI in chemotherapy monitoring of high
      grade malignant astrocytomas.
AB  - PURPOSE: To compare chemotherapy treatment monitoring in astrocytoma by
      201thallium single photon emission computed tomography (SPECT) and photon
      magnetic resonance spectroscopy (1H-MRS) with magnetic resonance imaging (MRI),
      and to evaluate the influence of morphological tumor changes on cerebral
      201thallium uptake and metabolic changes in 1H-MRS. MATERIALS AND METHODS: Six
      patients with highly malignant astrocytomas were followed with quantitative
      201thallium SPECT, MRI, and 1H-MRS during chemotherapy. Maximum follow-up
      included six examinations per patient by either method during 18 months. Criteria
      were set for: (1) regression (> or = 25% tumor reduction), (2) status quo (< 25%
      reduction and < 25% increase), and (3) progression of disease (> or = 25% tumor
      increase). Results were compared with the clinical state of disease. Changes of
      tumor volume, contrast enhancement, necrosis, hemorrhage and edema on MRI were
      compared to changes in 201thallium uptake volumes and 1H-MRS metabolite ratios.
      RESULTS: Six patients were followed with a total of twenty-four examinations with
      201thallium SPECT, MRI and 1H-MRS, respectively, between February 1997 and
      October 1998. Five patients developed clinical progression of disease, 4 out of 5
      cases showed SPECT progression, 4 out of 5 cases MRI progression, and 1 out of 2
      interpretable cases 1H-MRS progression at final assessment before clinical
      deterioration. During the phase of clinically stable disease; (A) the criterion
      for regression or status quo was met in 10 out of 13 assessments with SPECT, 11
      out of 13 with MRI, and 8 out of 9 interpretable 1H-MRS; (B) the criterion for
      progression was met in 3 out of 13 with SPECT, 2 out of 13 with MRI, and 1 out of
      9 interpretable 1H-MRS. The accuracy of SPECT, MRI, and 1H-MRS in identifying
      changes of tumor burden concordant with patients' clinical course was 78%, 83%,
      and 82%, respectively. SPECT regression was associated with MRI decrease of tumor
      size, contrast enhancement, edema and hemorrhage. SPECT progression was
      associated with MRI increase of the same parameters and the increase of necrosis.
      1H-MRS regression was associated with decrease of edema. 1H-MRS progression was
      associated with increase of tumor size, hemorrhage, and increase or decrease of
      contrast enhancement. CONCLUSIONS: Both 201thallium SPECT and 1H-MRS evaluation
      showed sensitivity for detection of astrocytoma progression. We did not find a
      higher accuracy of SPECT or MRS than of MRI in astrocytoma chemotherapy
      monitoring. Treatment induced MRI changes were associated with 201thallium uptake
      variations. 1H-MRS was difficult to apply for astrocytoma treatment monitoring.
      Improvements regarding size of measurement area such as multivoxel MRS and fat
      suppression pulses appeared desirable, and also the use of functional techniques
      with superior resolution such as dual isotope SPECT. However, our results suggest
      that 201thallium SPECT and 1H-MRS can provide additional information to MRI for
      chemotherapy efficacy evaluation in selected cases.

PMID- 10894369
TI  - Preliminary individual adjuvant therapy for gliomas based on the results of
      molecular biological analyses for drug-resistance genes.
AB  - New adjuvant therapy individualized by the results of reverse transcription
      polymerase chain reaction (RT-PCR) for drug-resistance genes has been used to
      treat malignant gliomas. Protocol studies for malignant gliomas were not so
      encouraging in their therapeutic results because of heterogeneity and the various
      drug-sensitivities of the tumors. Individualization of glioma therapy is
      recommended. Drug-resistance genes messenger ribonucleic acid (mRNA) expressions
      were investigated in drug-resistant human glioma cell lines derived from U87MG
      and 46 frozen samples of retrospectively examined neuroepithelial tumors (12 low
      grade neuroepithelial tumors, 16 Grade III gliomas, 11 glioblastomas, and 7 other
      malignant neuroepithelial tumors such as medulloblastomas and primitive
      neuroectodermal tumors) by RT-PCR with the specific primers for O6-methylguanine
      DNA methyltransferase (MGMT), multidrug-resistance gene 1 (MDR1), multidrug
      resistance-associated protein (MRP), and glutathione-S-transferase-pi (GST-pi).
      Thirty-seven preliminary individual adjuvant therapies (IAT) based on RT-PCR
      results, mainly in MGMT expression, were performed on 30 consecutive patients
      with neuroepithelial tumors. In the retrospectively examined series, the initial
      response to 1-(4-amino-2-methyl-5-pyrimidynyl) methyl-3-(2-chloroethyl)-3
      nitrosourea hydrochloride (ACNU) was correlated most significantly to the MGMT
      mRNA expression among 11 independent prognostic factors (p = 0.0037) in
      multivariate logistic regression analysis. In the preliminary IAT, 17 of 32
      evaluable therapies had a partial or complete response (53.1% response rate). Our
      IAT based on RT-PCR seemed to be more effective than conventional therapies for
      malignant gliomas.

PMID- 10894372
TI  - The management of pelvic chondrosarcoma in Japan. Japanese Musculo-Skeletal
      Oncology Group.
AB  - A review of 135 patients with pelvic chondrosarcoma who had been treated at 58
      institutions in Japan between 1989 and 1998. In this series ablative surgery was
      necessary in 14 patients, and a limb salvage procedure performed in 121 patients.
      The surgical margins were "intra-lesional" in 27 patients, "marginal" in 30,
      "wide" in 77 and "unspecified" in 1. Local recurrence occurred in 33 patients and
      distant metastases in 25. Post-operative infection occurred in 25 patients.
      Revision was performed in 10 patients. The oncological outcome was "disease free"
      in 92 patients, "alive with disease" in 17 and "dead because of the disease" in
      26. The cumulative prospective 10-year survival rate for all patients was 65%.
      The 6 statistically significant prognostic factors that determined the outcome
      were: - surgical stage, site of tumour, size of tumour, surgical margin,
      functional mobility and activity level after surgery. Excision of the tumour with
      a wide margin, or with a wide margin with partly marginal areas, and subsequent
      stable reconstruction are essential for improving the results of pelvic
      chondrosarcoma treatment.

PMID- 10894373
TI  - Preoperative estimation of metastatic vertebral tumors.
AB  - Total en bloc spondylectomy was performed in 22 patients with metastatic
      vertebral tumors. Osteolytic lesions were present in 15 cases while 7 cases had
      osteoblastic or mixed lesions. We measured the dimensions of the tumors
      preoperatively using magnetic resonance imaging (MRI) and computerized tomography
      (CT), and postoperatively by histological examination of the resected specimens.
      In the osteolytic group, the dorsoventral and transverse diameters of the
      metastatic tumor as measured on MRI were significantly greater compared to those
      determined by the histological examination. On the other hand, the same
      parameters measured by CT were smaller than the histologically determined
      dimensions. Although there were no significant differences between measurements
      of osteoblastic and osteolytic tumors, CT underestimated dimensions in
      osteoblastic or mixed tumors more than in those of osteolytic tumors. Estimation
      of tumor dimensions and local invasion using MRI and CT should be interpreted
      carefully.

PMID- 10894374
TI  - The value of a new method for assessing the separate functions of the long tracts
      and involved segments in patients with cervical myelopathy.
AB  - In order to assess accurately lesions of the spinal cord in patients with
      cervical myelopathy we have developed a new method of examination, which is based
      on the Japanese Orthopaedic Association (JOA) scoring system. The method attempts
      to assess separately the functions of the long tract and any involved cord
      segments in respect to the period after treatment. It was used in 117 consecutive
      patients who were divided into 2 groups based on whether or not there was a T2
      high-intensity lesion within the spinal cord, as revealed by a preoperative
      magnetic resonance imaging scan (MRI). The results of this method correlated well
      with the MRI findings. It was assumed that the degree of function of the upper
      limbs in patients with a T2-high-intensity lesion revealed more about a segment
      than about the long tract.

PMID- 10894375
TI  - Results of a single total knee prosthesis compared with multiple joint
      replacement in the lower limb.
AB  - We present the clinical results of total knee replacement (TKR) in 133 patients
      who had two or more major joints of the lower limbs replaced, and compare them to
      the outcome in 406 patients with an isolated TKR. 383 patients had osteoarthritis
      (OA) and 136 had rheumatoid arthritis (RA) and these were assessed separately. A
      meniscal bearing prosthesis was used. The functional score was high and there was
      no statistically significant difference in the incidence of complications between
      the two groups.

PMID- 10894376
TI  - Trapezoid osteotomy for slipped capital femoral epiphysis.
AB  - Twenty-three patients with chronic or acute to chronic slip of the capital
      femoral epiphysis were treated using a modified trapezoid osteotomy of the
      femoral neck. All slips were greater than 60 degrees. After a follow-up period of
      70 (54-93) months, the results were excellent or good in 18 hips, fair in 1, and
      poor in 4 hips. Avascular necrosis developed in 3 hips, and chondrolysis in 2.

PMID- 10894377
TI  - Core decompression shortens the duration of pain in bone marrow oedema syndrome.
AB  - We studied nine patients with 12 painful hips without apparent cause but with
      alteration of signal intensity on magnetic resonance imaging (MRI) consistent
      with bone-marrow oedema. The patients were randomly assigned to receive
      conservative or surgical treatment with core decompression. The duration of pain
      was significantly less in those treated surgically. Histological evaluation of
      the material obtained from 4 decompressions confirmed bone-marrow oedema without
      osteoporosis. Bone mineral density studies in 5 patients were normal. Although
      bone-marrow oedema of the femoral head is usually a self-limiting condition, we
      suggest that core decompression should be considered, as the symptoms may be
      prolonged and incapacitating.

PMID- 10894379
TI  - Proximally porous coated femoral stem in total hip replacement--5- to 13-year
      follow-up report.
AB  - A series of total hip replacements was performed using a proximally porous
      coated, tapered femoral stem system. At a mean follow-up of 8.1 (5-13) years, 80
      out of 107 hips were available for clinical and radiological examination. The
      mean age at the index procedure was 58.6 years. The mean Harris Hip Score at
      final follow-up was 91.7. Radiological ingrowth was observed in 77 femoral stems,
      2 stems were fibrous stable and 1 stem was loose.

PMID- 10894378
TI  - Matrix metalloproteinases in patients with osteoarthritis of the hip.
AB  - In 78 patients undergoing a total hip replacement we examined the production of
      matrix metalloproteinases (MMP) by the fibroblasts from the connective tissue of
      the acetabulum; we then correlated these findings with clinical and radiological
      characteristics of the same patients. In 53 patients only MMP-2 was produced; in
      15 cases MMP-1, -2 and -3 were present; and in 10 cases not only MMP-1, -2, -3
      but also MMP-9. Significant differences among the clinical and radiological
      parameters were found in the 3 subsets. A positive correlation between the
      production of MMP-9 and a rapid destruction of the hip joint was found.

PMID- 10894380
TI  - Femoral metastatic fractures treated with intramedullary nailing.
AB  - Between 1993 and 1998, 49 consecutive patients with impending or complete
      pathological fractures of the femur due to metastatic bone disease were treated
      with intramedullary nailing. Twenty-four were treated with a long Gamma nail and
      32 with an AO nail with a cephalomedullary spiral blade. Both implants gave a
      good functional result with relief of pain and improved mobility with no
      difference in morbidity between either group (P>0.05).

PMID- 10894381
TI  - The midvastus surgical approach in total knee arthroplasty.
AB  - We report a study of 2 surgical approaches to the knee in 42 consecutive patients
      undergoing a total arthroplasty. They were divided into 2 groups. In Group 1
      (n=17) the knee was exposed through classic medial parapatellar arthrotomy and in
      Group 2 (n=25) the knee was approached through the fibers of the medial vastus.
      Preoperative assessment did not reveal any statistical differences between the
      groups, and blood loss, operation time, biochemistry values and radiographic
      evaluation were also similar. However, a higher number of lateral releases, a
      loss of knee extension and a reduced range of motion were significantly
      associated with classical parapatellar arthrotomy. As the number of operative or
      postoperative complications was not increased, we recommend the mid-vastus
      approach for total knee arthroplasty.

PMID- 10894382
TI  - The management of medial ligament tears in patients with combined anterior
      cruciate and medial ligament lesions.
AB  - The management of patients with combined medial collateral (MCL) and anterior
      cruciate (ACL) rupture remains controversial. We studied 25 such patients who
      elected to have the ACL lesion treated conservatively; 14 underwent MCL repair
      with early mobilization and 11 were treated with immobilization for two weeks.
      The mean follow up was 5.9 years (2 to 11). There was no difference in the
      clinical assessment of ligamentous laxity, KT-1000 measurements or Tegner
      activity scores between the two groups but there were significantly higher
      Lysholm function scores in the operated group.

PMID- 10894383
TI  - Reactivation of tumor after 19 years? A case of local recurrence in clear cell
      chondrosarcoma.
AB  - Local recurrence of a clear cell chondrosarcoma of bone is reported arising 19
      years after resection of the original tumour.

PMID- 10894384
TI  - Cartilage and bone containing benign mesenchymoma of the thigh and popliteal
      fossa.
AB  - We report a case of a large cartilage and bone containing mesenchymoma of the
      thigh and popliteal fossa in a 56-year-old man. Mesenchymomas are rare tumors
      with a histologically benign pattern. They may be associated with morbidity as a
      result of local infiltrative growth.

PMID- 10894385
TI  - Colonna capsular arthroplasty and femoral head necrosis.

PMID- 10894386
TI  - The morphometry of the coracoid process--its aetiologic role in subacromial
      impingement syndrome.

PMID- 10894387
TI  - The use of copper(I) halides as a preparative tool
AB  - The use of copper(I) halides as a preparative tool is discussed with respect to
      the synthesis of adduct compounds with new polymeric and oligomeric main group
      molecules. By using this approach new polymers of main group elements--some of
      which have been predicted by theoretical investigations--can be obtained in a
      crystalline state and are therefore accessible for a basic structural
      characterization. Thus, it becomes possible to compare the structural data,
      experimental data, and theoretical results. Mixed copper halide chalcogenides are
      accessible when complex copper thiometalates and copper halides are combined.
      These solid-state compounds are of special interest since they provide
      experimental access to new main group molecules. In addition, they exhibit a high
      copper ion conductivity when certain structural features are present in the
      compounds. A survey is given of basic synthetic and general structural aspects.

PMID- 10894388
TI  - Traceless linkers--only disappearing links in solid-phase organic synthesis?
AB  - Traceless linkers, which enable the attachment of arenes and alkanes to a
      polymeric support, have received increased attention in recent years. These
      anchoring groups allow chemical transformations on the polymer-bound molecules,
      which can be cleaved from the resin leaving no residual functionality to bias the
      library. Various approaches based on different Group 14 to Group 16 heteroatoms
      have been developed in the past and used in new syntheses of diverse compound
      libraries.

PMID- 10894389
TI  - Direct comparison of electron transfer properties of two distinct semisynthetic
      triads with non-protein based triad: unambiguous experimental evidences on
      protein matrix effects.
AB  - In order to understand the roles of protein matrix in electron transfer processes
      (ET) within biological systems, a heme-based donor (Zn-heme: ZnPP)-sensitizer
      (Ru2+(bpy)3)-acceptor (cyclic viologen: BXV4+) triad 1 was used as a probe
      molecule. Two semi-synthetic systems, Cyt-b562(1) and Mb(1), in which the triad
      is incorporated into cytochrome b562 (Cyt-b562) or into myoglobin (Mb), were
      constructed by cofactor reconstitution. These two semi-synthetic proteins were
      compared with the triad itself (i.e., without the protein matrix) using
      absorption spectroscopy, steady state emission and excitation studies, laser
      flash photolysis experiments, and molecular modeling. Photoexcitation of the ZnPP
      moiety of Cyt-b562(1) or Mb(1) leads to a direct ET from the triplet state of
      ZnPP state (3ZnPP) to BXV4+ to generate a final charge-separated (CS) state, Cyt
      b562(Zn+)-Ru2+-BXV3+* or Mb(Zn+)-Ru2+-BXV3+*. On the other hand, direct ET from
      the excited ZnPP moiety to the BXV4+ moiety is also involved in 1 in the absence
      of the protein matrix, but the excited state of ZnPP involved is not 3ZnPP, but
      the singlet excited state (1ZnPP) in this pathway. When the Ru2+(bpy)3 moiety of
      Cyt-b562(1) or Mb(1) is excited, a stepwise ET relay occurs with the ion-pair,
      Cyt-b562(Zn)-Ru3+-BXV3+* or Mb(Zn)-Ru3*-BXV3+*, as an intermediate, leading to
      the same final CS state as that generated in the direct ET pathway. The lifetimes
      of the corresponding final CS states were determined to be 300 ns for 1 in the
      absence of the protein matrix, 600-900 ns for Cyt-b562(1) and 1.1-18 micros for
      Mb(1), the values of which are greatly affected by the protein matrix. Molecular
      modeling study of the three systems consistently explained the differences of
      their photophysical behavior.

PMID- 10894390
TI  - Solution- and soluble-polymer supported asymmetric syntheses of six-membered ring
      prostanoids.
AB  - An asymmetric synthesis of prostanoids containing a six-membered ring core
      structure (11a-homoprostaglandins), both in solution and using non-cross-linked
      polystyrene (NCPS) as a soluble support, was developed. Target molecule 1 was
      generated in a convergent fashion using a three-component coupling strategy,
      wherein chiral enone (R)-2 was the precursor of the central ring and the cuprate
      3 and triflate 4 were used to introduce the side chains. The chiral center of (R)
      2 directed the facial selectivity of the conjugate addition reaction which then
      dictated the stereochemical outcome of the subsequent alpha alkylation.
      Attachment of a six-membered ring scaffold to NCPS facilitated purification
      without compromising synthetic yields, still allowed 1H-NMR analysis of the
      intermediates in the synthesis, and provided an avenue for the construction of
      six-membered ring prostanoid libraries.

PMID- 10894391
TI  - Acid-base control for biocatalysis in organic media: new solid-state
      proton/cation buffers and an indicator
AB  - Although great care is generally taken to buffer aqueous enzyme reactions, active
      control of acid-base conditions for biocatalysis in low-water media is rarely
      considered. Here we describe a new class of solid-state acid-base buffers
      suitable for use in organic media. The buffers, composed of a zwitterion and its
      sodium salt, are able to set and maintain the ionisation state of an enzyme by
      the exchange of H+ and Na+ ions. Surprisingly, equilibrium is established between
      the different solid components quickly enough to provide a practical means of
      controlling acid-base conditions during biocatalysed reactions. We developed an
      organosoluble chromoionophore indicator to screen the behaviour of possible
      buffer pairs and quantify their relative H+/Na- exchange potential. The
      transesterification activity of an immobilised protease, subtilisin Carlsberg,
      was measured in toluene in the presence of a range of buffers. The large observed
      difference in rates showed good correlation with that expected from the measured
      exchange potentials. The maximum water activities accessible without formation of
      hydrates or solutions of the buffers are reported here. The indicator was also
      used to monitor, for the first time in situ, changes in the acid-base conditions
      of an enzyme-catalysed transesterification reaction in toluene. We found that
      even very minor amounts of an acidic by-product of hydrolysis were leading to
      protonation of the enzyme, resulting in rapid loss of activity. Addition of solid
      state buffer was able to prevent this process, shortening reaction times and
      improving yields. Solid-state buffers offer a general and inexpensive way of
      precisely controlling acid-base conditions in organic solvents and thus also have
      potential applications outside of biocatalysis.

PMID- 10894392
TI  - Difluoroboroxymolybdenum Fischer carbene complexes as precursors of acyl
      radicals: dimerization and trapping with electron-deficient alkenes
AB  - Pentacarbonyl acyl molybdates 1 react with boron trifluoride to give
      difluoroboroxy Fischer carbene complexes 2, which undergo loss of the metal
      fragment at room temperature to form 1,2-diketones 3, 1,2-hydroxy ketones 4, or
      dimers 5 through a dimerization or decarbonylation-dimerization process of acyl
      radicals. Decomposition of 2 in the presence of electron-deficient alkenes 11 and
      18 furnishes the two-, three-, and four-component coupling products 12, 13, 19,
      20, and 21.

PMID- 10894393
TI  - Template-induced and molecular recognition directed hierarchical generation of
      supramolecular assemblies from molecular strands
AB  - The linear oligo-isophthalamide strand 1 undergoes a conformational
      reorganization upon binding of a cyanuric acid template as effector to afford a
      helical disklike object possessing radially disposed alkyl residues. Solvophobic
      and stacking interactions, in turn, drive a "second level" self-assembly of the
      templated structure, the stacking of the helical disks, to yield fibers as
      revealed by electron microscopy. These data provide insight into the interplay of
      the different structural and interactional features of the molecular components
      towards the formation of supramolecular fibers through sequential hierarchical
      self-assembly events and suggest design strategies for the effector-controlled
      generation of related supramolecular assemblies.

PMID- 10894394
TI  - A flexible cyclophane: design, synthesis, and structure of a multibridged tris
      tetrathiafulvalene (TTF) macrocycle
AB  - The tris-tetrathiafulvalene (TTF) macrocycles 3 with a large end-cavity were
      effectively synthesized from the readily available tetrakis(cyanoethylthio)TTF by
      means of a selective deprotection/realkylation sequence followed by an
      intramolecular coupling reaction. Crystar structure analyses revealed that the
      neutral molecules include two (3a) or one chloroform molecule (3b) as solvent of
      crystallization inside the cavity, whereas the I3- salt of 3b, obtained by
      electrocrystallization, has a molecular structure which is different from that of
      the neutral molecule in that the cavity has completely collapsed.

PMID- 10894395
TI  - Functionalised oligoenes with unusual topologies: synthesis, electrochemistry and
      structural studies on redox-active
AB  - New [3]- and [4]-dendralenes bearing electron-donor 1,3-dithiole and ferrocene
      substituents have been synthesised. Compounds 8, 15 and 17 have been
      characterised by single-crystal X-ray diffraction. Two of the dithiole rings of 8
      are conjugated (dihedral angle 9 degrees), while the third dithiole ring is
      almost orthogonal to this plane, and hence its pi-electron system is isolated.
      For the dendralene precursor molecule 15, the substituted cyclopentadienyl ring,
      two C=C bonds and fused dithiole and dithiine rings comprise an extended pi
      conjugated system. In molecule 17 the potential conjugation path C(6)C(3)
      C(4)C(5)-C5Hs is distorted by an 8 degrees twist around the C(3)-C(4) bond and a
      7 degrees twist around the C(5)-C(21) bond, and the delocalisation along the
      chain is insignificant. Solution electrochemical data demonstrate that the
      dendralenes are strong pi-electron donors, which give rise to dication, radical
      trication or tetracation species. Spectroelectrochemical studies on compounds 7
      and 10 suggest that the radical species are situated within the linear 1,2
      ethylenediylidene moieties and that a conformational change may occur at the
      dication redox stage. UV/Vis spectroscopic data are consistent with poor cross
      conjugation in these systems.

PMID- 10894396
TI  - Gas-phase kinetic and mechanistic studies of some interconverting
      alkylcyclopropene pairs: involvement of dialkylvinylidene intermediates and their
      quantitative behaviour
AB  - The pyrolyses of two isomeric pairs of alkylcyclopropenes, namely 1,3-dimethyl
      (15) and 1-ethyl-cyclopropene (16), and 1,3,3-trimethyl-(5) and 1-isopropyl
      cyclopropene (17), have been studied in the gas phase. Complete product analyses
      at various conversions up to 95% were obtained for the decomposition of each
      compound at five temperatures over a 40 degrees C range. The time-evolution data
      showed that the isomerisation reactions 15<==>16 and 5<==>17 were occurring.
      Kinetic modelling of each system allowed the determination of rate constants for
      these and all other decomposition processes. Tests confirmed that all reactions
      were unimolecular and homogeneous. Arrhenius parameters are reported for overall
      reactions and individual product pathways. Further kinetic analysis allowed us to
      extract the propensities (at 500 K) for 1,3-C-H insertion of the
      dialkylvinylidene intermediates involved in the rearrangements as follows:
      k(prim):k(sec): k(tert)= 1:16.5:46.4. Additional experiments with 13C-labelled
      cyclopropenes yielded alkyl group migration aptitudes for the dialkylvinylidenes
      (from the pattern of 13C in the alkyne products) as follows: Me:Et:iPr=1:3.1:1.5.
      Explanations for these trends are given. Another important finding is that of the
      dramatic rate enhancements for 1,3-diene product formation from the 1
      alkylcyclopropenes; this can be explained by either hyperconjugative
      stabilisation of the vinylcarbene intermediates involved in this pathway, or
      their differing propensities to 1,2 H-shift. The observed large variations in
      product distribution amongst these four cyclopropenes is interpreted in terms of
      these specific effects on individual pathways.

PMID- 10894397
TI  - Activity enhancement by the support in the hydrogenation of C=C bonds over
      polymer-supported palladium catalysts
AB  - Four synthetic ion-exchange resins (AH, BH, CH, DH) of different
      hydrophilic/hydrophobic properties were used as supports for heterogeneous
      palladium catalysts (A, B, C, D). The resins contained styrene (STY) and 2
      (methacryloxy)ethylsulfonic acid (MESA) as the comonomers. Either divinylbenzene
      (DVB: CH, DH resins) or N,N'-methylenebisacrylamide (MBAA: AH, BH resins) were
      used as the cross-linker. AH contained also N,N-dimethylacrylamide (DMAA) as the
      third comonomer. The catalysts (Pd 0.25-0.45% w/w) were obtained by ion
      exchanging the acidic forms of the resins with [Pd(OAc)2] and reducing
      palladium(II) with excess sodium borohydride. The use of NaBH4 also ensured the
      neutralization of the acidic sites of the supports. No effect of the
      hydrophilic/hydrophobic properties of the supports was observed in the
      hydrogenation of cyclohexene and 2-cyclohexen-1-one in methanol, at 25 degrees C
      and 0.5, 1, and 1.5 MPa, respectively. However, catalysts A and B, containing
      amido groups provided by either DMAA or MBAA, proved to be more active than C and
      D. The observed activity enhancement was directly proportional to the nitrogen/
      palladium molar ratio in the catalysts. This finding suggests that amido groups
      promote palladium through a direct interaction with the metal surface.

PMID- 10894398
TI  - Stereoselective total synthesis of reveromycin B and C19-epi-reveromycin B.
AB  - Our studies toward the total synthesis of the reveromycin family of natural
      products are described herein. Our synthetic approach is efficient,
      stereocontrolled, and convergent and has resulted in the first synthesis of
      reveromycin B (4) and C19-epi-reveromycin B (55). Key steps of this successful
      strategy include: a modified Negishi coupling (construction of C7-C8 bond) and a
      Kishi-Nozaki reaction (construction of C19-C20 bond), which were employed in the
      attachment of the target side chains. The key building blocks for the total
      synthesis were thus defined as vinyl iodide 6, alkyne 7, and alkyne 8. Our
      synthesis illustrates the utility of the modified Negishi coupling for the
      construction of complex dienes, confirms the proposed stereochemistry of
      reveromycins and paves the way for the preparation of designed analogues for
      biological study.

PMID- 10894399
TI  - A complete kinetic study of GG versus AG plantination suggests that the doubly
      aquated derivatives of cisplatin are the actual DNA binding species.
AB  - The hairpin-stabilized double-stranded oligonucleotides d(TATGGTATT4ATACCATA) (I)
      and d(TATAGTATT4ATACTATA) (II) were allowed to react with the three aquated forms
      of the antitumor drug cisplatin (cis-[PtCl2(NH3)2], 1) which are likely
      candidates for DNA binding, that is, cis-[PtC1(NH3)2(H2O)]+ (2), cis
      [Pt(NH3)2(H2O)2]2+ (3), and its conjugate base cis-[Pt(OH)(NH3)2(H2O)]+ (4). The
      reaction between I and [Pt(NH3)3(H2O)]2+ (5) was also studied for comparison. All
      reactions were monitored by HPLC. The platination reactions of I and II were
      carried out in NaClO4 (0.1M) at 293 K and at a constant pH of 4.5 +/- 0.1 for 2,
      3, and 5. The data relative to the platination by 4 were obtained from
      measurements in unbuffered NaClO4 solutions (0.1M) at a starting pH close to
      neutrality, where 3 and 4 are present in equilibrium. In this case, a fit
      function describing the pH-time curve allowed the determination of the actual
      concentrations of 3, 4, and the dihydroxo complex. The platination rate constants
      characterizing the bimolecular reactions between either I or II and 2, 3, and 4
      were individually determined along with the rate constants for hydrolysis of the
      chloro-monoadducts and for the chelation reactions of the aqua-monoadducts. The
      reactivity of compounds 2-5, which have the general formula cis
      [Pt(NH3)2(H2O)(Y)]2+/-, decreases in the order 3>4>5>>2, that is, Y= H2O > OH-
      >NH3 >> Cl-, which is the order of decreasing hydrogen-bond donating ability of
      Y. Deprotonation of 3 to 4 reduces the reactivity of the platinum complex only by
      a factor of approximately equals 2, and both complexes discriminate between the
      different purines of I and II in the same manner. Whereas 3 and 4 react
      approximately three times faster with the GG sequence of I than with the AG
      sequence of II, 2 shows a similar reactivity towards both sequences. In view of
      the well-established preferential binding of cisplatin to GG sequences of DNA in
      vivo and in vitro, this result suggests that the actual DNA platination species
      are derived from double hydrolysis of cisplatin.

PMID- 10894400
TI  - Steel-promoted oxidation of olefins in supercritical carbon dioxide using
      dioxygen in the presence of aldehydes
AB  - Oxidation of olefins occurs effectively in supercritical carbon dioxide as the
      reaction medium with dioxygen as the primary oxidant and aldehydes as sacrificial
      co-oxidants. No catalyst is required, but the reaction is promoted by the
      stainless steel of the reactor walls. Depending on the substrate, vinylic
      oxidation or epoxidation can be the prevailing pathway. Epoxidation is
      particularly effective for substrates with internal double bonds and for long
      chain terminal olefins.

PMID- 10894401
TI  - Synthesis and characterization of tris-methacrylated 3,4,5-tris
AB  - The synthesis of liquid crystalline 3,4,5-tris(11-methacryloylundecyl-1
      oxybenzyloxy)benzoic acid, 2-methyl-(1,4,7,10,13-pentaoxacyclopentadecane)-3,4,5
      tris[4-(11-methacryloylundecyl-1-oxy)benzyloxy] benzoate and its 1:1 complex with
      sodium triflate is described. The observed mesophases were identified, by
      polarized optical microscopy and contact preparation techniques, to be of
      hexagonal columnar disordered structure. The amphiphiles form lyotropic columnar
      phases in concentrated methacrylate solvents, while at low solute contents
      supramolecular organogels emerge.

PMID- 10894402
TI  - Fast interconversion of C4H7+ cations in the gas phase and in a gaseous
      microsolvated environment
AB  - The equilibration of cyclobutyl 1 and 1' and the cyclopropylmethyl cation (2) has
      been studied in the gas phase by utilizing FT-ICR mass spectrometry and high
      pressure radiolytic techniques. A suitable gaseous nucleophile, C6X6 (X=H,D), was
      used to sample the equilibration of C4H7+ ions, produced from both cyclobutanol
      and cyclopropylmethanol. These are either dispersed in the bulk gas or confined
      within a C4H7+/C6X6 complex that contains a molecule of solvent (H2O). The
      analysis of the products shows that, irrespective of their source and of the
      intermolecular or intracomplex nature of the process, the C4H7+ ions undergo
      equilibration before they are trapped. The equilibrium (1+1')/2 ratio is very
      close to unity at 300 K, and the results from the intracomplex trapping
      experiment show that equilibration occurs within a time interval < or =10(-10) s.

PMID- 10894403
TI  - Asymmetric steering of the Mannich reaction with phthaloyl amino acids
AB  - Mannich-type reactions are powerful methods for the efficient synthesis of beta
      amino carbonyl compounds that are valuable intermediates for the construction of
      natural products, beta-peptides, and peptidomimetics. For the efficient steric
      steering of Mannich reactions a method was developed that consists in the
      treatment of imines with N-protected amino acid chlorides to give N
      acyliminiumion intermediates that are subsequently attacked with silylketene
      acetals. The reactions are run best at room temperature and in the absence of any
      Lewis acid. The highest stereoselectivity is observed if N,N-phthaloyl tert
      leucine is employed as chiral auxiliary and if N-aryl,C-aryl Schiffs bases are
      used that carry two ortho-substituents in either aromatic ring. Under these
      conditions the Mannich adducts are formed in preparatively useful yields and with
      excellent stereoselectivity (diastereomer ratio in general >99:1). The chiral
      auxiliary group is readily removed by 1) cleavage of the phthaloyl imide via
      reduction with NaBH4 and acid hydrolysis followed by 2) Edman degradation.

PMID- 10894404
TI  - Synthesis of expanded graphdiyne substructures
AB  - Graphdiyne (1) is a member of a novel family of interesting and potentially
      important allotropes of carbon. Reported herein are the synthesis and
      spectroscopic characterization of model substructures 2-6. The macrocycles were
      prepared by the intramolecular cyclization of suitable alpha,omega-polyynes. Key
      to the success of this approach was the development of an in situ
      protiodesilylation/alkynylation reaction utilizing reactive phenylbutadiyne
      synthons. This new method has allowed for the preparation of the largest, most
      complete substructures of the graphdiyne network to date (3-6).

PMID- 10894405
TI  - (E)-1-alkyl-4-
AB  - (E)-1-Alkyl-4-[2-(alkylsulfonyl)-1-ethenyl]pyridinium salts were synthesized in
      two steps. These sulfones were stable at pH 7.3 and underwent a nucleophilic
      vinylic substitution (S(N)V) with mercaptans, including thiouracile, to give the
      corresponding 4-(thiovinyl)-pyridinium salts. The X-ray diffraction structure of
      (E)-1-methyl-4-[2-(ethylsulfanyl)-1-ethenyl]pyridinium iodide indicated
      conjugation of the sulfur with the pyridinium ring. (Z)-1-Methyl-4-[2
      (methylsulfanyl)-1-ethenyl]pyridinium iodide, prepared from the corresponding
      thioether by reaction with methyl iodide in diethyl ether, underwent
      isomerization to the E isomer in a first-order reaction in deuterated [D6]DMSO
      with an activation energy of 14 kcalmol(-1). At pH 7, the (E)-1-methyl-4-[2
      (methylsulfonyl)-1-ethenyl]pyridinium iodide (19) reacted specifically with
      thiols. The reaction of this sulfone with glutathione in a TES buffer at pH 7 was
      a second-order reaction (k = 4,100 M(-1)s(-1) at 30 degrees C) and gave the
      corresponding substitution product with an intense long wavelength absorption
      band (lambdamax=360 nm, epsilon = 27,500 M(-1)cm(-1)). The modification of
      different enzymes of known structure with 19 showed the high selectivity of this
      reagent towards thiol groups and its usefulness in the quantitative determination
      of free thiol groups in proteins.

PMID- 10894406
TI  - 8-phenyl-10,10a-dihydropyrido
AB  - Base treatment of the pyridinium bromides 11a-e gives rise to the formation of
      the dihydropyridoazepines 14a-e as the only monomolecular products. The reaction
      takes place by initial deprotonation to the ylides 12, which undergo 8pi
      electrocyclization affording the seven-membered-ring systems; no products of a
      dipolar 6pi-cyclization were detected. On the basis of quantum mechanical
      calculations a rationalization of the periselectivity of the electrocyclization
      process is given.

PMID- 10894407
TI  - Pathologic detection of occult metastases in regional lymph nodes in patients
      with head and neck cancer.
AB  - Squamous carcinomas of the head and neck region are exceedingly common problems
      in the routine practice of head and neck tumour surgery. Well-defined treatment
      protocols have evolved to manage patients afflicted with such tumours. This
      article explores the role of the hospital pathologist in the detection of occult
      metastases. The conventional approach to evaluation of cervical nodes from a neck
      dissection is reviewed, and then the potential utility of more recently developed
      diagnostic approaches (such as immunohistochemistry and polymerase chain
      reaction) is explored.

PMID- 10894408
TI  - Otoprotectant minimizes hearing defects caused by Pseudomonas aeruginosa exotoxin
      A.
AB  - Exotoxin A, produced by Pseudomonas aeruginosa (PaExoA), penetrates from the
      middle ear in to the cochlea and causes sensorineural hearing loss (SNHL). In
      this investigation we studied electrophysiological changes in the albino rat
      following instillation of PaExoA and N(G)-nitro-L-arginine methyl ester (L-NAME),
      a known inhibitor of nitric oxide synthesis, into the middle ear. Hearing
      thresholds were measured by auditory brainstem response (ABR) technique.
      Latency/intensity curves were constructed to distinguish between cochlear and
      conductive components of hearing loss. PaExoA caused damage to cochleae and SNHL,
      mainly at high frequencies. This impairment was blocked by (L-NAME). It would
      appear that nitric oxide may be a significant link in the mechanism of SNHL
      caused by bacterial toxin. L-NAME acts as an otoprotectant against the
      deleterious action of PaExoA.

PMID- 10894409
TI  - Glutamate is the afferent neurotransmitter in the human cochlea.
AB  - Glutamate, the most important afferent neurotransmitter in the auditory system,
      is thought to be the afferent transmitter between the cochlear inner hair cells
      and afferent neurons, hitherto visualized only in the cochlea of animal species.
      It has been identified for the first time in sections from the human inner ear. L
      glutamate, NMDAR2B and the enzyme glutamine synthetase were identified by using
      monoclonal antibodies. The distribution pattern of the transmitter L-glutamate in
      the human cochlea is similar to that observed in other mammals. L-glutamate was
      identified adjacent to outer and inner hair cells and in the spiral ganglion.
      Similar distributions were found for glutamine synthetase and the ionotropic NMDA
      receptor subunit NMDAR2. The identification of neurotransmitters and their
      receptors in the human cochlea has implications for the pharmacotherapy of inner
      ear diseases.

PMID- 10894410
TI  - Dexamethasone modifies the effect of Pseudomonas aeruginosa exotoxin A on
      hearing.
AB  - In the present study, the protective effect of dexamethasone was analysed
      following exposure of the cochlea to Pseudomonas aeruginosa Exotoxin A (PaExoA).
      Four groups of albino Sprague-Dawley rats were used. 20 microl saline was
      instilled through the tympanic membrane into the round window niche (group A, n =
      4); 1 microg/20 microl dexamethasone sodium 21-phosphate (dexamethasone) solution
      was instilled (group B, n = 4); 1 microg/20 microl PaExoA solution was initially
      instilled followed 1 h later by 20 microl saline (group C, n = 6); and 1
      microg/20 microl PaExoA solution was initially instilled followed 1 h later by 1
      microg/20 microl dexamethasone solution (group D, n = 6). Frequency-specific (4,
      8, 10, 12, 16 and 20 kHz) auditory brainstem responses (ABR) were used to
      ascertain the threshold prior to exposure and 1, 2, 3, and 5 days and 1 and 2
      weeks afterwards. No threshold change was observed in groups A and B, whereas the
      animals in groups C and D showed some threshold elevation, that in D being
      smaller than that in C. There was a significant difference at the frequencies 12,
      16 and 20 kHz, 2 and 5 days after exposure. The intensity-latency (I-L) curve
      showed that in group D the cochlear component almost disappeared at high
      frequency one week after exposure. Our results indicate that dexamethasone can
      modify the effect of PaExoA caused by non-specific inflammation.

PMID- 10894411
TI  - Fixation of the electrode array with bone pate in cochlear implant surgery.
AB  - The aims of this study are to report on our experiences using a bone pate (a
      mixture of bone dust and fibrin glue) fixation technique of the Combi 40/Combi
      40+ electrode array during cochlear implant surgery. A retrospective study
      involving 57 patients implanted with Combi 40/Combi 40+ cochlear implants over 31
      months fixated with bone pate was performed, utilizing our electrical fitting
      data as well as re-operation and X-ray findings. We found no signs of electrode
      retraction in any of the 57 patients. Electrical fitting data showed no reduction
      in the number of active channels between the first and last times patients were
      evaluated (a period of 4-31 months). Furthermore, a comparison of X-rays
      performed within the first week following cochlear implant surgery and again 7-27
      months later showed no signs of electrode retraction in 10 patients. Three
      patients who required re-operations after implantation allowed us the opportunity
      to examine the effectiveness of the bone pate fixation and revealed new bone
      growth with the electrode fixed in place. Histological examinations of the newly
      built bone showed laminar and compact bone structures. The use of bone pate was
      thus found to be a suitable method of electrode fixation in cochlear implant
      surgery. Compared with other fixation methods, it is inexpensive and uses no
      foreign materials.

PMID- 10894412
TI  - Postnatal development of the tympanic cavity: a computer-aided reconstruction and
      measurement study.
AB  - A computer-aided 3-D reconstruction and measurement method was used to assess
      postnatal volume and height changes in the tympanic cavity. Materials used were
      14 normal human temporal bones obtained from 6 infants (under 1 year of age) and
      8 adults (over 18 years of age). After defining the boundaries of the tympanic
      cavity, its total volume and height and the volume and height of the epitympanum,
      mesotympanum and hypotympanum were measured. The relationship between the volume
      of the tympanic cavity and age, and the correlation between the volume of the
      tympanic cavity and the grade of pneumatization of the air cells were also
      studied. The average volume of the tympanic cavity in adults (640.1+/-69.1 mm3, n
      = 8) was about 1.5 times larger than the volume of the infant cavity (451.7+/
      68.2 mm3, n = 6). The hypotympanum increased most postnatally and the
      mesotympanum least. The volume of the tympanic cavity increased in proportion to
      increasing pneumatization in bone surrounding the cavity. The postnatal increase
      in the height of the tympanic cavity appears to be the major contributor to the
      increase in volume of the cavity. Postnatal changes in the tympanic cavity have
      clinical implications.

PMID- 10894413
TI  - What inner ear diseases cause benign paroxysmal positional vertigo?
AB  - Benign paroxysmal positional vertigo (BPPV) originating from the posterior
      semicircular canal (pSCC) is a common vestibular disorder that is easy to
      diagnose and usually easy to treat. The majority of patients with BPPV have no
      known inner ear disease; they have "primary" or "idiopathic" BPPV. However, a
      minority does have objective evidence of an inner ear disease on the same side as
      the BPPV and this group has "secondary" or "symptomatic" BPPV. Previous
      publications differ on the prevalence of secondary BPPV and about the types of
      inner ear diseases capable of causing it. In order to determine what proportion
      of patients have secondary as opposed to primary BPPV and which inner ear
      diseases are capable of causing secondary BPPV, we searched our database for the
      10-year period from 1988 to 1997 and found a total of 2847 patients with BPPV. Of
      these, 81 (3%) had definite pSCC-BPPV secondary to an ipsilateral inner ear
      disease. Sixteen had Meniere's disease, 24 had an acute unilateral peripheral
      vestibulopathy, 12 had a chronic unilateral peripheral vestibulopathy, 21 had
      chronic bilateral peripheral vestibulopathy and 8 had unilateral sensorineural
      hearing loss. It seems that any inner ear disease that detaches otoconia and yet
      does not totally destroy pSCC function can cause BPPV and that a case can be made
      for audiometry and caloric testing in all patients with BPPV.

PMID- 10894414
TI  - Effects of vestibular cerebellum lesion on motion sickness in rats.
AB  - The importance of the vestibular apparatus in the development of motion sickness
      is widely accepted, although the role of the vestibular cerebellum remains
      controversial. We examined the effects of vestibular cerebellum lesion on the
      development of motion sickness in rats. Rats do not vomit, but the behaviour
      known as "pica", the eating of non-nutritive substances, such as kaolin, can be
      used as an index of motion sickness. A 2 h load of hypergravity induced pica in
      rats, indicating that they suffered from motion sickness. Pica was induced by
      hypergravity load even after surgical lesion to the bilateral cerebellar
      flocculus or to the cerebellar vermis. We concluded that the vestibular
      cerebellum was not essential in the development of motion sickness in rats.

PMID- 10894415
TI  - Dizziness in discus throwers is related to motion sickness generated while
      spinning.
AB  - While both discus and hammer throwing involve rotating movements resulting in the
      throw of an object, discus throwers sometimes report dizziness, a condition never
      experienced by hammer throwers. We investigated whether this susceptibility was
      related to the sensitivity of the thrower or to the type of throwing achieved.
      For the latter, we compared the determining features of gesture, gaze
      stabilization and projectile trajectory in both sports. A total of 22 high-level
      sportsmen in these 2 disciplines, half of them practising both sports, were
      interviewed. Slow motion video recordings of discus and hammer throwing were
      examined to determine the visual referential, head movements and plantar surface
      support area involved at each stage of the motions. Discomfort was reported by
      59% of the sportsmen while throwing discus, but by none while throwing hammer.
      Because several individuals practised both sports, these results exclude the
      hypothesis of individual susceptibility to dizziness. Video analysis evidenced
      that during hammer throwing, visual bearings can be used more easily than during
      discus throwing. Moreover, there is a loss of plantar afferents and generation of
      head movements liable to induce motion sickness, such as Coriolis acceleration.
      In conclusion, although hammer and discus-throwing present numerous similarities,
      we demonstrate here that crucial differences in the specific execution of each
      sport are responsible for the dizziness experienced by discus throwers.

PMID- 10894416
TI  - Influence of age and presbyacusis on DPOAE.
AB  - The influence of presbyacusis on distortion-product otoacoustic emissions
      (DPOAEs) was studied on 180 ears of 96 normal-hearing subjects. The subjects'
      ages were distributed equally and ranged from 14 to 82 years. It was shown that
      there is a highly significant decrease in DPOAE amplitudes during the ageing
      process. By means of special statistical procedures, such as partial correlation
      and multiple regression, it was proved that the main reason for this is
      deterioration in pure-tone thresholds. However, other age-related effects were
      determined and were also found to lead to a further decrease in DPOAE amplitudes.
      The latter might be due to middle ear alterations in elderly people. Knowledge of
      the influence of presbyacusis on DPOAE is important if DPOAEs are to be used in
      expert assessment of inner ear disorders, for example, occupational noise-induced
      hearing loss.

PMID- 10894417
TI  - Cholinergic influence on vestibular stimulation-induced locus coeruleus
      inhibition in rats.
AB  - In our previous study, caloric stimulation (CS) of the vestibular apparatus
      inhibited noradrenergic neuronal activity in the locus coeruleus (LC) in urethane
      anaesthetized rats. Therefore, the inhibition of LC noradrenergic neurons is
      involved in vestibulo-autonomic responses. Since motion sickness can be cured by
      scopolamine, cholinergic neuron system may also be involved in vestibulo
      autonomic responses. The present study examined the effects of
      intracerebroventricular injection of ethylcholine mustard aziridinium ion
      (AF64A), a presynaptic cholinergic neurotoxin, on CS-induced LC inhibition. In
      AF64A-treated rats, the CS-induced LC inhibition was less pronounced than in
      normal rats. In a subsequent series of experiments, the intravenous injection of
      scopolamine blocked the CS-induced LC inhibition. These findings suggest that
      central cholinergic neurons are associated with noradrenergic neuronal inhibition
      during the vestibulo-autonomic reflex.

PMID- 10894418
TI  - Influence of maxillary morphology on nasal airway resistance in Marfan's
      syndrome.
AB  - High nasal airway resistance (NAR) has been reported in Marfan's syndrome, and
      this appears to contribute to the development of obstructive sleep apnoea in
      these patients. The cause of high NAR in Marfan's syndrome is unknown, but these
      patients characteristically have a narrow maxilla, which could have an influence
      on nasal dimensions. The aim of this study was to define the mechanism(s)
      mediating high NAR in Marfan's syndrome. Five patients with Marfan's syndrome
      (mean age 29+/-4 (SEM) years) were compared with an equivalent number of normal
      control subjects (31+/-1 years). NAR was measured by posterior rhinomanometry,
      before and after topical decongestant, nasal stenting, or both. Dental
      impressions were taken to evaluate maxillary arch morphology, allowing
      measurement of the following lateral distances: inter-canine (ICD), inter
      premolar (IPD), and inter-molar (IMD). NAR (at a flow of 500 ccm/s) was
      considerably higher in patients compared with controls at baseline (0.93+/-0.08
      vs 0.35+/-0.08 Pa/ccm/s, p < 0.001), and following decongestant and/or stenting.
      The maxillary arch was considerably narrower in patients. There were strong
      inverse correlations between the lateral maxillary dimensions and NAR after nasal
      decongestant, with or without stenting. These results indicate a strong
      association between maxillary width and NAR, and suggest that maxillary
      constriction is the dominant mechanism for the high NAR in Marfan's syndrome. The
      therapeutic implications of this finding warrant further investigation.

PMID- 10894419
TI  - Diagnosing respiratory events and tracing air flow by internal thermistors.
AB  - We have developed a new method to measure flow in patients with sleep-related
      breathing disorders (SRBD). These flow sensors are modified thermistors located
      in the same sensors we use for pressure measurement in the upper airways to find
      the obstructive segments during apnoeas. The aim of this study was to test if
      using internal thermistors as indicator of air flow has advantages compared with
      the external thermistor method in detecting respiratory events. A total of 50
      consecutive patients with an apnoea-hypopnoea index (AHI) of more than 15 were
      studied. A standard nocturnal polysomnography (PSG) with both internal and
      external thermistors was performed in all patients. To estimate the patients'
      AHI, a detailed analysis viewing all parameters except external and internal
      thermistors was performed. This was followed by an analysis viewing only internal
      thermistors signals indicating airflow in the pharynx, and finally an analysis
      viewing only external thermistor signals indicating air flow at the mouth and
      nose. Mean AHI measured by the three methods showed 49.8 (SD 23.4) by the PSG,
      47.8 (SD 24.9) by internal thermistors alone, and 31.5 (SD 22.2) by external
      thermistors. There was no statistical difference between AHI detected by PSG and
      internal thermistors, but highly significant differences between PSG and external
      thermistors (p < 0.001). The external thermistors missed an average of almost 20
      respiratory events per hour.

PMID- 10894420
TI  - Nasal nitric oxide is reduced in patients with HIV.
AB  - The gas nitric oxide (NO) is present in high concentrations in human nasal
      airways. Since NO is known to inhibit the growth of bacteria and viruses, it has
      been suggested that airborne NO represents the first line of defence against
      pathogens in the upper airways. Low nasal NO levels have been reported previously
      in patients susceptible to upper airway infection. Since HIV-positive patients
      are at risk for respiratory tract infections, including sinusitis, we studied the
      levels of NO in the upper and lower airways of these patients. A cross-sectional
      study with age-matched HIV patients and controls was carried out. Nasal and
      orally exhaled NO were measured in 31 HIV patients and 26 controls using a well
      established chemiluminescence method developed for measurements of gaseous NO in
      the airways. Nasal NO was 21%, lower (p < 0.05, Student's t-test) in HIV patients
      than in controls, whereas orally exhaled NO did not differ between the two
      groups. We conclude that nasal NO is reduced in patients with HIV infection. The
      reduction in nasal NO may contribute to the decreased resistance to airway
      infections in these patients.

PMID- 10894421
TI  - Ultrastructural characterizations of olfactory pathway neurons in layer II of the
      entorhinal cortex in monkey.
AB  - The somatic size, shape, dendritic and axonal morphology, and synaptology of
      representative neurons in layer II of the primate entorhinal cortex (EC) were
      analyzed. Layer II "islands" contained large spinous multipolar cells with
      triangular somata and local circuit axons in addition to multipolar neurons with
      large, radially arrayed, aspinous, primary processes and thick tapering axons.
      Small pyramidal neurons with a single, spinous, apical primary segment that
      bifurcated a short distance from the somata were also found in layer II.
      Subsequent spinous segments of these neurons with long terminal segments
      exhibited a paucity of branching in addition to having thick axons tapering into
      subjacent layers. The importance of providing these additional axonal, dendritic,
      and synaptic characterizations lies in the contextual role these neurons play in
      the connectional patterns of the EC with regard to olfaction, olfactory memory,
      and pathological variations.

PMID- 10894422
TI  - Fine-structural investigations of the effect of nCPAP-mask application on the
      nasal mucosa.
AB  - The treatment success of nasal continuous positive airway pressure (nCPAP)
      therapy is dependent, on the one hand, on the achieved relief of complaints and,
      on the other hand, on long-term patient compliance and avoidance of compliance
      related complaints. Next to the problem of mask application, nasal complaints
      comprise the most frequently reported side-effects and are among the primary
      factors causing nCPAP-therapy to be discontinued prematurely. To assess the
      morphological changes in the nasal mucosa during nCPAP-therapy, we excised
      specimens of nasal mucosa tissue from 10 patients with obstructive sleep apnoea
      syndrome (OSAS) before and 3-10 months after establishing nCPAP-mask compliance.
      The specimens were examined by electron microscopy. In all these patients
      compliance with the CPAP-mask marked the initial part of therapy. In addition,
      mucociliary clearance was assessed by the saccharin test before and after
      therapy. In all patients the nasal epithelium underwent fundamental changes upon
      CPAP-therapy, which became manifest as modifications in the shape of epithelial
      cells, conglutination and clumping of the microvilli, and the appearance of
      immunocompetent cells. Once patients were nCPAP-mask compliant, mucociliary
      clearance was distinctly prolonged in all cases. A successful therapeutic concept
      should provide normalization of room temperature and air humidity once nCPAP-mask
      compliance has been achieved and include regular assessment of the condition of
      the mucosa in the upper respiratory tract. Only by these measures can nasal
      complications be countered or given therapy at an early stage.

PMID- 10894423
TI  - Swallowing dysfunction related to snoring: a videoradiographic study.
AB  - Biopsy studies of the soft palatal and oropharyngeal tissues in habitual snorers
      and patients suffering from obstructive sleep apnoea have shown signs of
      neurogenic lesions. These lesions might affect the pharyngeal swallowing
      function, which is dependent on adequate sensitivity. The objective of the
      present study was to test the hypothesis that snoring is associated with aberrant
      pharyngeal swallowing function. Forty-one consecutive patients without dysphagia,
      seeking medical attention because of heavy snoring and various degrees of daytime
      sleepiness, were prospectively selected. Fifteen non-snoring volunteers without
      dysphagia served as controls. Patients and volunteers were videoradiographically
      examined in lateral and posteroanterior views during the oral and pharyngeal
      phases of swallowing. The hypothesis was verified. Snoring patients demonstrated
      deviant pharyngeal swallowing function seven times more frequently than did the
      non-snoring volunteers. Deviant pharyngeal swallowing function was observed in 22
      (54%) of the snorers compared with 1 (7%) of the non-snoring volunteers. Impaired
      bolus control with premature leakage of bolus into the pharynx and a delayed
      evocation of the swallowing reflex was the most common finding, followed by bolus
      residual in the pharynx and laryngeal penetration. The conclusion was that
      snoring is associated with subclinical pharyngeal swallowing dysfunction.

PMID- 10894424
TI  - Subglottic airway becomes stable with age in the human infant larynx.
AB  - Development of the mucosal defence system and its relationship to the
      pathogenesis of laryngeal diseases was studied by examining the changes in the
      laryngeal structures at the level of subglottic larynx of 59 human infants who
      died within 1 year of birth. By making a transverse section at the level of the
      cricoid cartilage, the area and diameter of each subglottic structure were
      examined using an image analysis system. The results were analysed, not only by
      their age at death, but also based on the total development score. The areas of
      the whole structure, cricoid ring, subglottic mucosa and inner cavity (available
      area) increased in close correlation with the total development score. In
      contrast to the increased diameter of the inner cavity, the thickness of the
      mucosa was almost the same size. These results indicate the stability of the
      subglottic airway with advancing age in the human infant larynx.

PMID- 10894425
TI  - Dental maturity in Finns and the problem of missing teeth.
AB  - Development of teeth was studied from 2483 dental panoramic tomograms of 1651
      healthy Finns ranging in age from 2 to 25 years. Dental maturity was assessed
      using a method based on developmental stages of 7 left mandibular teeth. We give
      sex-specific tables of maturity scores as a function of ages and of ages as a
      function of maturity scores. Also generated are percentile graphs for visual
      evaluations of dental maturity in children and adolescents. Since maturity scales
      do not tolerate any missing data, a great limitation for their use, we have
      developed linear regression models for predicting the formation stages of each of
      the 7 mandibular teeth. It was easiest to predict the formation stage of the
      mandibular first molars (correct in 87% within the study material) and most
      difficult to predict second molars and second premolars (correct in 69% and 70%,
      respectively). We expect the data and formulae presented in this study to prove
      useful in research and in clinical and forensic dentistry.

PMID- 10894426
TI  - Permeability of protective gloves by HEMA and TEGDMA in the presence of solvents.
AB  - The breakthrough times and permeation rates of two commonly used allergenic
      components in dentin bonding agents or resins, HEMA and TEGDMA, were measured for
      5 types of latex gloves and 5 types of nitrile gloves. In addition, the
      breakthrough times and permeation rates for the gloves were measured for HEMA and
      TEGDMA when diluted with either ethanol or acetone-solvents often appearing in
      dentin bonding agents. The mean breakthrough times for the 5 latex gloves for
      HEMA and TEGDMA, concentrated, diluted in ethanol, or diluted in acetone, were
      4.9, 4.8, and 2.8 min, respectively. For the 5 nitrile gloves the equivalent
      breakthrough times were 15.7, 9.9, and 2.8 min, respectively. There were great
      variations between the various gloves, and 1 nitrile glove showed a breakthrough
      time of 28-30 min when tested with concentrated HEMA and TEGDMA. Compared to
      latex gloves, nitrile gloves have a longer-lasting protection against skin
      contamination with methacrylates in the absence of solvents. The longer
      protection was reduced or not present for methacrylates diluted in organic
      solvents, especially acetone. In addition, the nitrile gloves showed fairly high
      permeation rates in the presence of this solvent. The results indicate that latex
      and nitrile gloves only give a limited protection against allergenic
      methacrylates in dentin bonding agents when they contain acetone.

PMID- 10894427
TI  - Model of the dentist-patient consultation in a clinic specializing in the
      treatment of dental phobic patients: a qualitative study.
AB  - Thirty semi-structured interviews were conducted with 5 dentists (3 male and 2
      female) after first and second consultations with 15 newly enrolled dental phobic
      patients (2 male and 13 female) in a clinic specializing in the treatment of
      odontophobia. Analysis of the transcribed interviews was influenced by the
      principles of grounded theory. Five concepts/higher-order categories were
      grounded in the data: 1 core category: 'Relatedness, based on affective resonance
      and concordant roles' and 4 additional higher-order categories: 'the dental
      phobic patient's emotions'; 'the patient's verbal and non-verbal cues'; 'the
      dentist's role as a clinician: professional interpersonal skills'; and 'the
      dentist's role as a fellow-being: general interpersonal skills'. The model
      developed describes the dynamics of the dentist patient interaction and has a
      theoretical application.

PMID- 10894428
TI  - First two-year complications of fixed partial dentures, eight units or more.
      Swedish Guarantee Insurance claims.
AB  - This study is an analysis of fixed partial dentures (FPDs), 8 units or more, that
      failed or suffered severe complications within the first 2 years after
      cementation. The material consists of claims to the Swedish Guarantee Insurance
      for Fixed Prosthodontics. Claim reports, radiographs, etc. were available. Over a
      6-month period, 36 FPDs were sampled, 34 of which were made by general
      practitioners. The sampling resulted in 41 complications in 26 maxillary and 10
      mandibular FPDs, 29 of which were made in metal-ceramics. The mean extension was
      10.9 units, with an abutment/pontic ratio of 1.4; 40.6% of the abutments were
      root-canal treated and supplied with root posts. The complications were: metal
      framework fractures 41%, loss of retention 24%, porcelain fractures 17%,
      tooth/root fractures 10%, and miscellaneous 7%. The high proportion of metal
      framework fractures is not in accordance with other studies of FPD complications.
      No factor that could explain this high frequency could be identified. The fact
      that the selection of FPD complications applied to the first 2 years only, that
      the FPDs had been constructed by general practitioners, and that there were many
      root-canal-treated abutments and distal extension cantilever pontics, might be
      factors of importance.

PMID- 10894429
TI  - Interfacial adaptation of a Class II polyacid-modified resin composite/resin
      composite laminate restoration in vivo.
AB  - The aim of this in vivo study was to evaluate the interfacial adaptation of Class
      II resin composite open sandwich restorations with a polyacid-modified resin
      composite as a stress-absorbing layer (PMRC/RC). Twenty Class II box-shaped,
      enamel-bordered cavities were prepared in 10 premolars scheduled to be extracted
      for orthodontic reasons. An open PMRC/RC sandwich restoration was placed in 1 of
      the cavities of each tooth. The first layer, PMRC, in the proximal box extended
      to the periphery in the cervical part of the cavity. The following RC layers were
      placed with a horizontally incremental technique. The PMRC was excluded from the
      control cavity. The teeth were extracted after 1 month and the interfacial
      adaptation of the restorations was studied with quantitative scanning electron
      microscope analysis using a replicate technique. Gap-free interfacial adaptation
      was observed for the PMRC/RC and RC restorations in cervical enamel in 97% and
      73%, respectively (P = 0.006). The gap-free scores for dentin were 87% and 64%,
      respectively (P = 0.022). Excellent interfacial adaptation was observed in both
      groups for the occlusal enamel 99% and 100%, respectively. The adaptation to
      occlusal enamel for the direct resin composite restorations was significantly
      better than to dentin or cervical enamel. A higher frequency of enamel fractures
      was observed parallel to the cervical margins compared to the occlusal. No dentin
      fractures were observed in the experimental groups. The PMRC/RC sandwich
      technique showed a statistically significant improved interfacial adaptation to
      dentin and cervical enamel in Class II enamel-bordered cavities. The clinical
      significance of the differences has to be evaluated.

PMID- 10894430
TI  - Popliteal pterygium syndrome in a Swedish family--clinical findings and genetic
      analysis with the van der Woude syndrome locus at 1q32-q41.
AB  - The present study describes a Swedish family in which the mother and her son were
      affected with signs of popliteal pterygium syndrome (PPS, OMIM 119500). Both
      individuals had bilateral complete cleft lip and palate, oral synechiae,
      paramedian pits on the lower lip, toe syndactyly and a piece of triangular skin
      overgrowth on the great toes. The son also presented with soft tissue syndactyly
      of the 2nd and 3rd fingers. Although popliteal pterygium was not found, the above
      clinical features were diagnostic for PPS. Chromosomal abnormalities were not
      revealed in either case by cytogenetic analyses. A test for microdeletion in the
      VWS region at 1q32-q41 was performed in the family using 5 polymorphic
      microsatellite markers from the region. The affected son was found to be
      heterozygous for all 5 markers, suggesting that microdeletion at the VWS region
      was unlikely. The VWS locus, however, was not excluded by haplotype analysis of
      the family.

PMID- 10894431
TI  - Trends in reasons for tooth extractions in Norway from 1968 to 1998.
AB  - The aims of this study were (i) to determine the reasons for extraction of
      permanent teeth in Norway in 1998 and (ii) to describe changes in reasons for
      extraction in time-trend and quasi-longitudinal perspectives over 30 years based
      on three cross-sectional studies. The 1998 data were obtained from questionnaires
      distributed to a national random sample of 1,500 dentists, of whom 1,008
      responded (67%). A total of 1,495 teeth were extracted for 1,164 patients (age 10
      92 years) during a period of 2 weeks. Caries accounted for 40% of the extractions
      and periodontal diseases for 24%. Caries was the primary reason in patients 10-45
      years old, while periodontal diseases dominated among adults > 45 years old. In a
      time-trend perspective, among patients > or = 21 years, a significant decrease in
      the proportion of extractions because of caries was observed between 1968 and
      1988, while non-significant changes were found between 1988 and 1998. Extractions
      because of periodontal disease accounted for about 26% in all surveys. Followed
      longitudinally, the three cohorts born 1923-32, 1933-42, 1943-52 showed a
      decrease in the proportion of extractions due to caries, and an increase in the
      proportion of periodontal extractions during the period, more so between 1968 and
      1988 than between 1988 and 1998. The three cohorts showed a variable trend of
      change, which may indicate that period and age effects do not necessarily operate
      in the same direction.

PMID- 10894432
TI  - Cardiovascular happenings in Europe.

PMID- 10894433
TI  - Right ventricular infarction--diagnosis and treatment.
AB  - Right ventricular infarction (RVI) as assessed by various diagnostic methods
      accompanies inferior-posterior wall myocardial infarction (MI) in 30 to 50% of
      patients. Recognition of the syndrome of RVI is important as it defines a
      significant clinical entity, which is associated with considerable immediate
      morbidity and mortality and has a well-delineated set of priorities for its
      management. Patients may clinically present with hypotension, elevated jugular
      venous pulse (JVP), and occasionally shock, all in the presence of clear lung
      fields. The ST-segment elevation of > or = 0.1 mV in the right precordial leads
      V4R is a readily available electrocardiographic sign used for diagnosis of RVI.
      Other diagnostic approaches for assessing RVI include echocardiography,
      radionuclide ventriculography, technetium pyrophosphate scanning, and hemodynamic
      measurements. The proper management of RVI includes volume loading to maintain
      adequate right ventricular preload, ionotropic support, and maintenance of
      atrioventricular synchrony. Reperfusion therapy should be initiated at the
      earliest signs of right ventricular dysfunction. Finally, complete recovery over
      a period of weeks to months is a rule in a majority of patients, suggesting right
      ventricular "stunning" rather than irreversible necrosis has occurred.

PMID- 10894434
TI  - Low-molecular-weight heparins in acute myocardial infarction: rationale and
      results of a pilot study.
AB  - BACKGROUND: Antithrombotic adjuncts to fibrinolytic drugs for acute myocardial
      infarction increase the rate and speed of infarct artery recanalization.
      HYPOTHESIS: A low-molecular-weight heparin might be preferable to unfractionated
      heparin for this indication, as it has been shown to be in several other thrombus
      related vascular disorders. METHODS: We performed a pilot study in 20 patients,
      all receiving aspirin and recombinant tissue plasminogen activator. Randomization
      was to standard dose intravenous unfractionated heparin or enoxaparin (the first
      dose given intravenously and followed by a subcutaneous administration). The
      endpoint was stability of anticoagulant effect. RESULTS: Enoxaparin produced
      stable therapeutic anti-Xa levels with minimal effect on activated partial
      thromboplastin times. Unfractionated heparin produced wide swings of these
      parameters, often outside desired levels. CONCLUSIONS: Enoxaparin may be a better
      antithrombotic agent than conventional unfractionated heparin when used in
      conjunction with fibrinolytics.

PMID- 10894435
TI  - Prognostic role of plasminogen-activator-inhibitor-1 levels in treatment with
      streptokinase of patients with acute myocardial infarction.
AB  - BACKGROUND: The antifibrinolytic effect of plasminogen-activator-inhibitor type 1
      (PAI-1) may be responsible for delays in reperfusion and/or reinfarctions after
      streptokinase (STK) therapy in patients with acute myocardial infarction (AMI).
      HYPOTHESIS: This study aimed to demonstrate the prognostic role of pretreatment
      PAI-1 levels for the outcome of STK therapy in patients with AMI, depending on
      reperfusion and/ or reinfarction. METHODS: The mean pretreatment PAI-1 level of
      104 patients with AMI, treated with STK, determined by chromogenic method, was
      5.8 +/- 8.6 U/ml, range 0.3-66.2 U/ml. Streptokinase therapy was successful when
      reperfusion was achieved, as assessed noninvasively, without subsequent
      reinfarction; it failed when reperfusion was delayed and/or reinfarction
      developed. RESULTS: Fibrinolysis with STK failed significantly in patients with
      elevated pretreatment PAI-1 levels (p < 0.05), especially with levels >4.0 U/ml
      (p< 0.01). The mean pretreatment PAI-1 level was significantly higher in
      unsuccessfully treated patients. Multivariate statistical testing demonstrated
      that among pretreatment variables, elevated PAI-1 activity was the most
      significant independent risk factor of failed fibrinolysis with STK. CONCLUSIONS:
      Among pretreatment variables, elevated pretreatment PAI-1 activity in patients
      with AMI was the most significant independent risk factor of failed fibrinolysis
      with STK, especially at levels > 4.0 U/ml.

PMID- 10894436
TI  - Resolution of ST-segment elevation after streptokinase therapy in anterior versus
      inferior wall myocardial infarction.
AB  - BACKGROUND: Resolution of ST-segment elevation is the best bedside predictor of
      myocardial reperfusion. HYPOTHESIS: This study was conducted to examine the
      resolution of ST-segment elevation after streptokinase therapy in anterior versus
      inferior acute myocardial infarction (MI) and to corroborate it with
      echocardiographic and coronary angiographic data. METHODS: The study population
      consisted of 70 patients, 35 each in the anterior and inferior MI groups. The
      electrocardiograms (ECGs) were recorded before, on completion of, and on Days 1
      and 2 post streptokinase therapy. The resolution of ST segment determined from
      post-streptokinase ECGs was compared between the two groups and correlated with
      echocardiographic and coronary angiographic data. RESULTS: On completion of and
      on Day 1 post streptokinase therapy, ST-segment resolution in both groups was not
      significantly different. On Day 2 post streptokinase therapy, resolution of the
      ST segment per lead was significantly lower in anterior than that in inferior MI
      (61 +/- 21% anterior vs. 77 +/- 21% inferior, p 0.003). The number of patients
      with akinesis of infarct-related ventricular wall was significantly higher (17
      anterior vs. 7 inferior, p 0.02), and left ventricular ejection fraction was
      significantly lower in anterior MI (39 +/- 7% anterior vs. 48 +/- 8% inferior, p
      < 0.01). There was no significant difference in coronary angiographic data. One
      patient in each group demonstrated normal coronary arteries. CONCLUSIONS: The
      resolution of ST-segment elevation on the completion of and on Day 1 post
      streptokinase therapy was comparable between anterior and inferior MI. The
      significantly less frequent resolution of ST-segment elevation in anterior MI on
      Day 2 post streptokinase could be due to more akinesis, larger infarct size, and
      worse systolic function rather than due to failure to open the infarct-related
      vessel.

PMID- 10894437
TI  - Angiographic and scintigraphic (perfusion and electrocardiogram-gated SPECT)
      correlates of clinical presentation in unstable angina.
AB  - BACKGROUND: Braunwald classification can be used as a measure of the acuteness or
      severity of clinical presentation of unstable angina. Gating perfusion images
      might provide additional information to that obtained from angiography, allowing
      correlations between the coronary anatomy and extent of myocardium at risk via
      simultaneous perfusion/function assessment. HYPOTHESIS: The aim of this study was
      to determine the relation between the highest levels of the Braunwald
      classification (class III = rest angina within 48 h of presentation; class C =
      postinfarction angina; class c = refractory angina) and the angiographic
      findings, and the extent ofperfusion and segmental wall motion abnormalities
      using technetium-99m ((99m)Tc) sestamibi-gated single-photon emission computed
      tomography (SPECT) imaging. METHODS: The study group consisted of 86 patients
      with unstable angina who underwent rest gated (99m)Tc sestamibi SPECT imaging and
      coronary angiography. Perfusion was graded on a 5-point scale (0 = normal; 4 =
      absent uptake) and wall motion on a 4-point scale (0 = akinesia/dyskinesia; 3 =
      normal) using the 20 segment model. Perfusion (PI) and wall motion indices (WMI)
      were calculated by adding the score of all segments and dividing this by 20. The
      localization, the degree of stenosis, and the morphology of the culprit lesion
      were assessed. Multivariate analysis was performed to identify the independent
      predictors of class III, C, and c angina. RESULTS: Perfusion index was higher and
      WMI was lower in classes III, C, and c than in classes < III, < C, and < c,
      respectively (all p < 0.001). Class III angina was associated with PI (p
      <0.0001), WMI (p< 0.0001), complex morphology (p = 0.01), and decreased
      Thrombolysis in Myocardial Infarction (TIMI) flow (p = 0.002); class C angina
      with PI (p < 0.0001), WMI (p< 0.0001), intracoronary thrombus (p = 0.007), and
      decreased TIMI flow (p = 0.003); and class c angina with PI (p = 0.005) and WMI
      (p = 0.006). CONCLUSION: The highest levels of the Braunwald classification are
      associated with a greater size and intensity of myocardial perfusion and wall
      motion abnormalities and with the angiographic findings of complex morphology,
      intracoronary thrombus, and decreased TIMI flow.

PMID- 10894438
TI  - The effect of transient balloon occlusion of the mitral valve on left atrial
      appendage blood flow velocity and spontaneous echo contrast.
AB  - BACKGROUND: Spontaneous echo contrast (SEC) is a phenomenon that is commonly seen
      in areas of blood stasis. It is a slowly moving, cloud-like swirling pattern of
      "smoke" or increased echogenicity recorded on echocardiography. SEC is commonly
      seen in the left atrium of patients with mitral stenosis or atrial fibrillation.
      The presence of SEC has been shown to be a marker of increased thromboembolic
      risk. HYPOTHESIS: By using transesophageal echocardiography during percutaneous
      balloon mitral valvotomy (PBMV), the study investigated the relationship between
      SEC and varying left atrial appendage (LAA) blood flow velocity in the human
      heart. METHODS: Thirty-five patients with rheumatic mitral stenosis underwent
      percutaneous balloon mitral valvotomy with intraoperative transesophageal
      echocardiography monitoring. We alternatively measured LAA velocities and
      observed the left atrium for various grades of SEC (0 = none to 4 = severe)
      before and after each balloon inflation. RESULTS: Left atrial appendage maximal
      ejection velocity was reduced from 35 +/- 14 to 6 +/- 2 mm/s at peak balloon
      inflation and increased to 40 +/- 16 mm/s after balloon deflation. In comparison
      with the values before balloon inflation and after balloon deflation, LAA
      velocities were significantly lower (p < 0.001). New or increased SEC grade was
      observed during 54 of 61 (88%) inflations and unchanged in 7 (12%) inflations at
      peak balloon inflation. Spontaneous echo contrast became lower in grade after 55
      balloon deflations (90%), completely disappeared after 18 deflations (30%), and
      remained unchanged after 6 deflations (10%). The mean time to achieve maximal SEC
      grade (2.5 +/- 1.2 s) coincided with the mean time to trough LAA velocities (2.3
      +/- 1.1 s) after balloon inflation. Upon deflation, the mean time to lowest SEC
      grade (2.9 +/- 1.8 s) coincided with mean time to achieve maximal LAA velocities
      (2.7 +/- 1.6 s). CONCLUSION: During balloon inflation, the severity of SEC was
      enhanced with corresponding reduction in LAA flow velocity. Upon balloon
      deflation, SEC lightens or disappears with increase in LAA flow velocity.

PMID- 10894439
TI  - Intravascular ultrasound predictors of major adverse cardiac events in patients
      with unstable angina.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) predictors of native culprit lesion
      morphology for occurrence of major adverse cardiac events (MACE) have not been
      reported. Moreover, the published data on IVUS predictors of restenosis include
      patients with stable and unstable angina, although the development and
      progression of atherosclerosis related to unstable coronary syndrome is different
      from that of stable angina. HYPOTHESIS: This study investigated whether IVUS
      derived qualitative and quantitative parameters of native (preangioplastic)
      plaque morphologic features can predict major adverse cardiac events in patients
      with unstable angina. METHODS: Clinical (age, gender, coronary risk factors),
      qualitative and quantitative angiographic (lesion localization, morphology, pre-
      and postangioplastic minimal lumen diameter, reference diameter, and percent
      diameter stenosis), and IVUS variables (soft/fibrocalcific plaque, calcification,
      presence of thrombus or plaque disruption, different types of arterial
      remodeling, pre- or postangioplastic minimal lumen, external elastic membrane and
      plaque cross-sectional area, and plaque burden of the target lesion and reference
      segments) were analyzed by regression analyses using the Cox model, assuming
      proportional hazards. RESULTS: Of 60 consecutively enrolled patients, 21 suffered
      from MACE, while 39 remained event-free during the followup period. Multivariate
      regression analyses revealed that the presence of adaptive remodeling [p =
      0.0177, risk ratio (RR) = 3.108, with 95% confidence interval (CI) = 1.371-8.289]
      and the preangioplastic lumen cross-sectional area (p = 0.0130, RR = 0.869, with
      95% CI = 0.667-0.913) are independent predictors of MACE during follow-up, as is
      postangioplastic angiographic minimal lumen diameter (p = 0.0330, RR = 0.715 with
      95% CI = 0.678-0.812). CONCLUSIONS: Adaptive remodeling and preangioplastic lumen
      cross-sectional area determined by IVUS and postangioplastic minimal lumen
      diameter calculated by quantitative angiography are significant independent
      predictors of time-dependent MACE in patients with unstable angina.

PMID- 10894440
TI  - Relation of transesophageal echocardiographic findings to subtypes of cerebral
      infarction in patients with atrial fibrillation.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) has been used to identify the
      potential risk for cardiogenic embolism in patients with atrial fibrillation
      (AF). However, ischemic stroke in patients with AF is not always attributable to
      embolism. Identification of the risk of embolic versus atherothrombotic stroke
      should lead to the optimal individualized management of patients with AF.
      HYPOTHESIS: The goal of the study was to determine the relation between cortical
      infarction and perforating infarction and TEE findings in patients with AF.
      METHODS: We investigated the clinical usefulness of TEE in the risk
      stratification of clinical subtyping of the cerebral infarctions which were
      divided into two territories of the cortical branch (cortical infarction due to
      embolism) and deep perforators (perforating infarction due to atherothrombosis).
      Left atrial spontaneous echo contrast, peak flow velocity in the left atrial
      appendage, and generalized atherosclerosis as estimated by the intima-media wall
      thickness of the thoracic aorta were assessed by TEE in 118 consecutive patients
      with either paroxysmal (n = 44) or chronic (n = 74) AF. All patients underwent
      either brain computed tomography or magnetic resonance imaging. RESULTS: Cortical
      and perforating infarction was found in 39 and 18% of patients, respectively. The
      grade of spontaneous echo contrast was higher in patients with than in those
      without cortical infarction (p < 0.05). In contrast, patients with perforating
      infarction showed significant increase in the aortic wall thickness when compared
      with patients without perforating infarction (p < 0.05). In addition,
      multivariate logistic analysis revealed that spontaneous echo contrast was an
      independent predictor of cortical infarction, while intima-media wall thickness
      of the aorta, hypertension, and age were useful in predicting the risk of
      perforating infarction. CONCLUSIONS: Transesophageal echocardiography has a
      potential role in the risk stratification for cortical and perforating infarction
      in patients with AF.

PMID- 10894441
TI  - Circadian heart rate response to chronotherapy versus conventional therapy in
      patients with hypertension and myocardial ischemia.
AB  - BACKGROUND: Changes in heart rate (HR) may contribute to the higher incidence of
      cardiovascular events in the morning. HYPOTHESIS: The objectives of this analysis
      were to assess HR patterns in two populations (patients with chronic stable
      angina or stage I to III hypertension) and to compare the effects of various
      antianginal and antihypertensive treatments on HR. METHODS: This was a
      retrospective analysis of HR data from two clinical trials evaluating the
      efficacy of controlled-onset, extended-release (COER)-verapamil. The effects of
      COER-verapamil were compared with placebo, nifedipine gastrointestinal
      therapeutic system (GITS), amlodipine, and the combination of amlodipine and
      atenolol. RESULTS: In patients with angina (n = 498), the change from baseline in
      HR following 4 weeks of treatment was -6.7 +/- 10.5 beats/min in the COER
      verapamil group, -10.8 +/- 10.8 beats/min in the amlodipine/atenolol group, + 2.5
      +/- 9.1 beats/ min in the amlodipine monotherapy group, and -1.3 +/- 10.5
      beats/min in the placebo group (p<0.001). Data were stratified based on whether
      patients experienced asymptomatic ischemia during baseline ambulatory
      electrocardiographic monitoring. The circadian HR pattern was morphologically
      similar in all groups; however, differences in the magnitude of HR response were
      evident. In the subset of patients with asymptomatic ischemia (n = 101),
      treatment with amlodipine monotherapy increased HR compared with placebo. In this
      same subset of patients, HR reductions were achieved with COER-verapamil and
      amlodipine/atenolol. In patients with hypertension (n = 557), the change in HR
      following 10 weeks of treatment was -3.3 beats/min for patients treated with COER
      verapamil compared with + 2.0 beats/min for patients treated with nifedipine GITS
      (p < 0.0001, between-group differences). CONCLUSION: This analysis demonstrates
      that morphologically similar circadian patterns of HR occur in both hypertensive
      patients and those with angina. In addition, significant variation exists among
      antianginal and antihypertensive agents regarding HR effects.

PMID- 10894442
TI  - Failure of magnesium to protect isolated cardiomyocytes from effects of hypoxia
      or metabolic poisoning.
AB  - BACKGROUND: MgSO4 appears to reduce infarct size in animal models of myocardial
      infarction-reperfusion, but only if given before reperfusion. The mechanisms
      underlying this effect have not been established, nor has the discrepancy between
      these results and the lack of efficacy in the Fourth International Study of
      Infarct Survival (ISIS-4) been explained. HYPOTHESIS: The study was undertaken to
      examine the hypothesis that Mg2+ protects myocardium threatened by ischemia.
      METHODS: We studied the effects of extracellular magnesium [Mg2+](e) at 0.6 and
      1.8 mmol/l on isolated myocytes exposed to 2.5 mmol/l NaCN + 5 mmol/l 2
      deoxyglucose or to profound hypoxia. RESULTS: Nonpaced cells shortened at a mean
      of 8.8 min after onset of metabolic inhibition in [Mg2+](e) = 1.8 mmol/l, 9.6 min
      in [Mg2+](e) = 0.6 mmol/l (not significant). Paced cells shortened after 9.5 min
      in [Mg2+](e) = 1.8 mmol/l, 10.2 min at [Mg2+](e) = 0.6 mmol/l. On washout of
      inhibitors, 93% of cells underwent hypercontracture at [Mg2+](e) = 1.8 mmol/l,
      94.8% at [Mg2+](e) = 0.6 mmol/l. During hypoxia, nonpaced cells in [Mg2+](e) =
      1.8 mmol/l shortened after 67 +/- 11 min compared with 62.5 +/- 28 min at
      [Mg2+](e) = 0.6 mmol/l. Paced cells shortened after 25.8 +/- 12.9 min at
      [Mg2+](e) = 1.8 mmol/l and after 28.7 +/- 13.6 min at [Mg2+]e = 0.6 mmol/l.
      Although there was a trend toward longer survival at higher [Mg2+](e), the
      difference was small and not significant (p > 0.05, Student's paired t-test).
      CONCLUSION: We find no evidence to support the hypothesis that [Mg2+] protects
      myocardium threatened by ischemia. This is consistent with clinical data but
      contradicts data from animal experiments.

PMID- 10894443
TI  - Effects of glibenclamide, a K(ATP) channel blocker, on warm-up phenomenon in type
      II diabetic patients with chronic stable angina pectoris.
AB  - BACKGROUND: Warm-up phenomenon, one of the clinical models of ischemic
      preconditioning, refers to an increased tolerance to myocardial ischemia during
      the second of two consecutive exercise tests. HYPOTHESIS: Blockers of K(ATP)
      channels, such as the sulfonylurea drugs, can induce loss of ischemic
      preconditioning. This study aimed to investigate the effects of glibenclamide, a
      sulfonylurea with a high affinity for myocardial K(ATP) channels, on the results
      of two consecutive exercise tests in diabetic patients with coronary artery
      disease. METHODS: Eighteen type II diabetic patients with chronic stable angina
      pectoris participated in this study. All patients underwent two consecutive
      treadmill exercise tests with a recovery period of 15 min in fasting state. On
      the day after these exercise tests, 10 mg oral glibenclamide was given to the
      same patients and 30 min later 200 ml of 30% glucose solution was given orally.
      Half an hour later, which is the time of peak plasma levels of glibenclamide, two
      exercise tests were repeated consecutively with a 15 min recovery period.
      RESULTS: There was no difference in blood glucose levels before and after
      exercise tests on each day (p > 0.05). Without glibenclamide, heart rate, rate
      pressure product at 1.5 mm ST depression, and peak exercise increased
      significantly (p < 0.05). Time to 1.5 mm ST-segment depression and onset of pain,
      as well as duration of exercise also increased, but ST-segment depression and ST
      recovery time significantly decreased (p < 0.05). In contrast, these values did
      not significantly change after glibenclamide (p>0.05), with a significant drug
      test interaction (p < 0.05, at two-way ANOVA). CONCLUSIONS: Glibenclamide, an
      oral hypoglycemic agent with a K(ATP) channel-blocker activity, with a 10 mg oral
      dose, abolished the warm-up phenomenon which is a clinical finding of ischemic
      preconditioning on two consecutive exercise tests. Therefore, glibenclamide
      should be used carefully in patients with coronary heart disease and diabetes
      mellitus since this agent leads to a decrease in ischemic threshold and exercise
      capacity.

PMID- 10894444
TI  - The incidence and consequences of mental disturbances in elderly patients post
      cardiac surgery--a comparison with younger patients.
AB  - BACKGROUND: Limited data exist about the incidence and consequences of mental
      confusion following open heart surgery in different age groups. Likewise, little
      is known about preoperative predictors of mental confusion. METHODS: Two-hundred
      consecutive patients, aged > or =75 years (Group 1), and 400 procedure- and
      gender-matched younger patients (Group 2) who underwent coronary or valvular
      surgery were included in a prospective study. The relation between postoperative
      mental confusion, mortality, morbidity, and quality of life was studied. RESULTS:
      Mental confusion was present in 11.8% Group 2 and 22.6% Group 1 patients. The
      incidence was higher after valvular surgery. Preoperative risk factors in Group 1
      patients were diabetes mellitus, a history of heart failure, weak carotid
      pulsations, and repeat surgery. Late mortality, after a median follow-up duration
      of 31 months, was significantly worse in patients who were confused, which was
      related to the underlying disease. Recovery of quality of life was clearly
      diminished in elderly patients with confusion in contrast to younger patients.
      CONCLUSION: Postoperative mental confusion has a high incidence in the elderly
      population and is associated with a diminished quality of life.

PMID- 10894445
TI  - Constrictive pericarditis.

PMID- 10894446
TI  - Cox-Maze procedure for treatment of atrial flutter associated with an atrial
      septal defect.
AB  - A 52-year-old man presented with atrial flutter and was found to have an atrial
      septal defect (ASD). The paper describes an effective surgical approach for the
      treatment of this atrial arrhythmia utilizing a right sided Cox-maze III
      procedure concomitant with ASD closure. Review of the literature and clinical
      implications are discussed.

PMID- 10894447
TI  - Profiles in cardiology. Rudolph Virchow and cellular pathology.

PMID- 10894448
TI  - Can we prevent congestive heart failure? Excerpts from a symposium.

PMID- 10894449
TI  - Overview of the relationship between ischemia and congestive heart failure.
AB  - Ischemic heart disease is the principal etiology of heart failure in the Western
      world. Myocardial ischemia is important in cardiac remodeling, a process that
      leads to a progressive change in the shape and size of the heart and
      significantly worsens the prognosis of patients with heart failure. Preventing
      ischemic events, therefore, is an important goal in the management of patients
      with coronary artery disease. Statins have been shown to reduce the number of
      ischemic events in these patients, whereas the benefit of beta-blocker and
      aldosterone antagonist therapy on ischemic causes of heart failure remains
      unclear. Several large trials involving patients with asymptomatic left
      ventricular dysfunction after myocardial infarction or heart failure have shown
      that angiotensin-converting enzyme (ACE) inhibitors reduce the incidence of
      progressive heart failure, death, and ischemic events, thus establishing ACE
      inhibitors as first-line therapy for these patients. Other lines of evidence have
      suggested that ACE inhibitor therapy may also benefit patients with preserved
      left ventricular function, a hypothesis that is being evaluated in three large,
      controlled, randomized trials. One of these trials, the Heart Outcomes Prevention
      Evaluation (HOPE) study, was terminated prematurely because it demonstrated the
      significant positive effects of the ACE inhibitor ramipril on cardiovascular
      outcomes in patients with coronary artery disease and preserved left ventricular
      function. A growing body of data confirms the relationship between ischemia and
      heart failure and the benefits of ACE inhibitor treatment in a broad range of
      high-risk patients.

PMID- 10894450
TI  - The anti-ischemic potential of angiotensin-converting enzyme inhibition: insights
      from the heart outcomes prevention evaluation trial.
AB  - Therapy with an angiotensin-converting enzyme (ACE) inhibitor is established for
      reducing excessive blood pressure, reducing mortality in patients with congestive
      heart failure (CHF), preventing the development of CHF in patients with
      asymptomatic left ventricular (LV) dysfunction, and preventing death and CHF when
      initiated early after the onset of acute myocardial infarction (MI). Although
      these benefits have been attributed largely to hemodynamic mechanisms, recent
      preclinical and clinical evidence reveal ACE inhibition as potent in preventing
      ischemic events and in blocking an array of ischemic processes, including
      atherogenesis. A major contributor to this new evidence is the large, placebo
      controlled Heart Outcomes Prevention Evaluation (HOPE) trial, which found that
      the ACE inhibitor ramipril ( 10 mg daily) prevented MI and other ischemic events
      in patients with a broad range of cardiovascular (CV) risks (including coronary
      artery disease, stroke, peripheral vascular disease, or diabetes plus one
      additional risk factor) but no LV dysfunction or history of heart failure at
      baseline. The data from the HOPE trial suggest a greatly expanded role for
      ramipril in the prevention and management of CV disease.

PMID- 10894451
TI  - Class effects and evidence-based medicine.
AB  - Drugs grouped into a therapeutic class on the basis of a common mechanism of
      action often have considerably different pharmacodynamic and pharmacokinetic
      properties. Among angiotensin-converting enzyme (ACE) inhibitors, differences
      with potential clinical relevance include potency, whether the drug is an active
      compound or requires metabolic activation, lipophilicity, route(s) of
      elimination, and half-life. Large clinical trials have documented the clinical
      benefits of several ACE inhibitors in various patient populations, and many
      clinical effects of ACE inhibitors are likely to be the same. However, there are
      possible quantitative differences among ACE inhibitors that may alter the overall
      therapeutic benefits for specific patient populations and indications.
      Equipotency in terms of clinical efficacy is difficult to determine. Since the
      concept of "class effect" is a term of convenience that has no universally
      accepted definition and subsequently should not form the basis for the practice
      of evidence-based medicine, untested drugs of a "class" should be considered to
      be unproven drugs.

PMID- 10894452
TI  - Consensus statement: aerosols and delivery devices. American Association for
      Respiratory Care.

PMID- 10894453
TI  - Influence of inspiratory flow rate, particle size, and airway caliber on
      aerosolized drug delivery to the lung.
AB  - A number of studies in the literature support the use of fine aerosols of drug,
      inhaled at low IFRs to target peripheral airways, with the objective of improving
      clinical responses to inhaled therapy (Fig. 8). Attempts have been made to
      separate response due to changes in total administered dose or the surface
      concentration of the dose from response due to changes in site of deposition-
      both are affected by the particle size of the aerosol, with IFR additionally
      influencing the latter. The tools for measuring dose and distribution have
      improved over the last 10-15 years, and thus we should expect greater accuracy in
      these measurements for assessing drug delivery to the lung. There are still
      issues, though, in producing radiolabeled (99m)technetium aerosols that are
      precise markers for the pharmaceutical product being tested and in quantitating
      absolute doses deposited in the lung. PET isotopes may provide the means for
      directly labelling a drug and perhaps can offer an alternative for making these
      measurements in the future, but deposition measurements should not be used in
      isolation; protocols should incorporate clinical tests to provide parallel
      therapeutic data in response to inhalation of the drug by the various patient
      populations being studied.

PMID- 10894454
TI  - Nebulizers: principles and performance.
AB  - Nebulizers have been used clinically for many years. Despite the increasing use
      of metered-dose inhalers and dry powder inhalers, it is likely that nebulizers
      will continue to be used in selected patients. A number of factors affect
      nebulizer performance, and these should be appreciated by clinicians who use
      these devices. Several new designs have recently become available that improve
      the performance of the nebulizer, but their cost-effectiveness remains to be
      determined.

PMID- 10894455
TI  - Metered-dose inhalers, dry powder inhalers, and transitions.
AB  - Since 1956, the pMDI has become the most commonly prescribed and used aerosol
      device in the world. While concerns about global warming have led to a worldwide
      ban of CFCs, new HFA-propelled pMDIs are in development, requiring an
      evolutionary transition in the technology. The phase-out of CFC-propelled pMDIs
      has stimulated the development of more efficient DPIs, but issues such as cost of
      device production, inspiratory flow requirement, and the effects of ambient
      humidity on drug delivery may limit DPI acceptance, and industry projections
      suggest that the DPI will not completely replace the pMDI. Holding chambers may
      perform differently with HFA-propelled pMDIs, but HFA-propelled pMDIs generally
      appear to cause less oropharyngeal deposition and to improve lung delivery while
      continuing to provide protection from poor hand-breath coordination. The initial
      offerings of the emerging HFA-propelled pMDI technology appear to be resulting in
      an improved pMDI.

PMID- 10894456
TI  - Special problems in aerosol delivery: artificial airways.
AB  - Several factors interact in influencing aerosol deposition during mechanical
      ventilation. Among these factors, the artificial airway is a significant barrier
      for aerosol deposition. Earlier studies overemphasized the impediments created by
      the artificial airway to aerosol delivery, because the aerosol generator was
      placed adjacent to the endotracheal tube or was connected to it. When the aerosol
      generator is placed away from the endotracheal tube, the fraction that deposits
      within the tube is reduced and greater aerosol deposition occurs in the lungs.
      The type of aerosol generator used and the ventilator settings have a greater
      effect than the size of the tube on the amount of aerosol that deposits in the
      artificial airway. To minimize aerosol loss within artificial airways, an
      endotracheal tube of the appropriate size should be selected. "Priming" the tube
      with a few doses of aerosol before use decreases the electrostatic charge on its
      walls and may reduce aerosol deposition within the tube. Similarly, using a
      spacer with the MDI, and placement of the combination in the inspiratory limb at
      a distance of at least 15 cm from the endotracheal tube reduces aerosol loss
      within the endotracheal tube. Use of nebulizers that produce submicronic
      aerosols, and placing them closer to the ventilator instead of closer to the
      patient also decreases aerosol impaction in the artificial airway. Use of a low
      inspiratory flow (30-60 L/min in adults), higher duty cycle (> 0.3), and helium
      oxygen mixture instead of air or oxygen are other measures to reduce aerosol loss
      in the airway and thereby improve aerosol delivery to the lower respiratory tract
      of mechanically ventilated patients.

PMID- 10894457
TI  - Special problems in aerosol delivery: neonatal and pediatric considerations.
AB  - Identification of the determinants of efficient aerosol delivery and the specific
      challenges of aerosol delivery to infants and children can facilitate a
      systematic approach to optimize aerosol delivery to this population. There are
      inherent anatomical, physiologic, pathophysiologic, and technical limitations of
      aerosol efficiency in infants and young children. Nevertheless, one can enhance
      aerosol efficiency through application of sound principles of aerosol delivery
      and by exerting control over factors that are amenable to intervention.
      Improvements in aerosol formulations and delivery systems are being made that
      will enhance efficiency, decrease risk, and reduce waste and cost. Attention to
      aerosol particle size (1-3 microm mass median aerodynamic diameter and geometric
      standard deviation < 2 microm), and the concentration of this respirable particle
      fraction produced by an aerosol system may enhance delivery through endotracheal
      tubes and to the lower respiratory tract in infants and children with low V(T)
      and low inspiratory rates. Attention to the choice of delivery system and to
      details of proper MDI technique (shaking, priming, immediate actuation, and
      avoiding multiple actuations prior to inhalation), choice of the aerosol spacer
      and patient interface (type of face mask, endotracheal tube, mouthpiece), spacer
      cleaning, and consideration of the medicine to be aerosolized (solution or
      suspension, viscosity) permit adjustment of the aerosol regimen to optimize
      delivery. All the patient-related, system-related, and operator-dependent
      considerations combined can greatly impact aerosol delivery efficacy and improve
      therapeutic response. Therefore, education and motivation of medical personnel,
      parents and caregivers, and patients regarding factors that influence aerosol
      efficiency and teaching of proper technique must be prioritized in order to
      improve aerosol delivery. Aerosol therapy to all patients, especially infants and
      young children, would be well served if we had a clear understanding of the
      efficiency and functional differences among the various drugs and devices. These
      are substantive issues with daily therapeutic impact that have received
      increasingly outspoken concern over the past decade by aerosol scientists and
      clinicians. These issues must be given due attention by drug and device
      manufacturers as well as by regulatory agencies. The medication, the device, and
      the conditions under which they are tested must be considered together and
      studied as thoroughly as the medications themselves with respect to total output
      and particle size distribution. As noted by Bisgaard, medication dose
      recommendations are useless unless the device and technique used are specified.
      Medication dose recommendation could be facilitated by setting equivalent
      standards for generic and brand-name medications and devices. In addition,
      standardization of in vitro models with better replicas of infants' and
      children's anatomy (oropharynx, upper airways), and better in vitro lung models,
      plus utilization of realistic breathing patterns of infants and children will
      improve in vitro prediction of the in vivo dose delivered to lower airways. This
      would greatly facilitate selection of delivery systems under specific
      circumstances for infants and children of various ages). Safety profile,
      therapeutic efficacy, and efficiency of aerosolized medications delivered to
      infants and children need to be rigorously studied. This is particularly true for
      medications with potentially great benefit but possible adverse effects, such as
      inhaled glucocorticoid therapy in extremely premature infants. Common sense,
      ethics, and due respect for the same high standard of approval requirements of
      adults and older children should motivate further research in understanding and
      improving aerosol delivery in infants and young children.

PMID- 10894459
TI  - Aerosolized antibiotics: current and future.
AB  - Aerosolized antibiotic therapy appears to have potential for targeted therapy to
      the airways and deep lung to prevent VAP in patients at high risk for this
      disease. The definition of that high-risk population is important if this model
      is to be successful. We are attempting to define susceptible patients by
      measuring the volume of airway secretions, which mirrors the inflammation milieu
      of the central airways. Elevated sputum volume is marked by heavy growth of
      pathogenic organisms and high levels of inflammatory cytokines. Large-scale
      clinical trials are necessary to define the usefulness of these surrogates in
      defining a targeted population and for assessing the potential of aerosolized
      antibiotic prophylactic therapy for preventing pneumonia and mortality. If
      successful, the aerosol approach may avoid systemic therapy and its associated
      complications.

PMID- 10894458
TI  - Drug properties affecting aerosol behavior.
AB  - The widespread use of aerosol therapy in the treatment of pulmonary diseases is
      based on optimizing drug properties and aerodynamic behavior of airborne
      particulates. In order to understand drug properties and aerodynamic behavior, it
      is important to recognize that each category of inhaler delivers a product with
      different physicochemical characteristics, and that these properties determine
      the site of deposition and the mechanism of clearance from the lungs. The complex
      interplay of these properties and the physiology and anatomy of the lungs must be
      considered to fully understand the implications for drug delivery. The
      aerodynamic behavior of aerosols under various inspiratory flow conditions
      influences the site of deposition. Once the particle comes to rest in the lungs,
      mechanisms of clearance are invoked, including dissolution and absorption, or,
      for more insoluble materials, mucociliary transport or cell-mediated transport.
      Finally the pharmacokinetics of drug disposition dictate the pharmacodynamic
      effects of the drugs responsible for efficacy.

PMID- 10894460
TI  - Aerosolized medications for altering lung surface active properties.
AB  - Surface active material is important in the function of both the infant and adult
      lung. In the premature infant, surfactant depletion results in the requirement
      for very high distending pressures to open alveoli. As a consequence, shunt,
      hypoxemia, and right ventricular dysfunction occur. Surfactant replacement,
      especially by the direct instillation approach, has been proven effective in
      improving clinical outcome under these circumstances. Problems with surfactant
      instillation include the "fluid bolus" effect and concerns about optimal
      distribution of the instilled material. Recent improvements in aerosol systems
      have created interest in using aerosol delivery to reduce the total dose of
      surfactant required to treat RDS. In adult acute lung injury, surfactant
      dysfunction, rather than depletion, is the problem. Simple phospholipid
      replacement strategies thus may not be effective. Instead, surfactant delivery
      strategies aimed at regional targeting with surfactants having the necessary
      associated proteins may be the goal in ARDS. In adults, several instillation
      trials are underway, but there is also a hope that an aerosol strategy might also
      be tried. The aerosol route may be particularly useful if a high-efficiency
      aerosol system (eg, one distal to an endotracheal tube) can be shown to be
      effective. Other surface active materials exist and there are small studies
      showing benefit when large instilled doses of these materials are given. These
      materials, however, have never been studied as aerosols.

PMID- 10894461
TI  - Experimental macromolecular aerosol therapy.
AB  - These novel and experimental therapies have the potential of drastically altering
      our understanding of and approach to airway disease. We indeed live in
      interesting times.

PMID- 10894462
TI  - Methods of calculating lung delivery and deposition of aerosol particles.
AB  - Lung deposition of aerosol is measured by a variety of methods. Total lung
      deposition can be measured by monitoring inhaled and exhaled aerosols in situ by
      laser photometry or by collecting the aerosols on filters. The measurements can
      be performed accurately for stable monodisperse aerosols. However, for
      polydisperse and/or unstable hygroscopic aerosols, measurement methods are
      limited and often unreliable. Regional deposition is assessed primarily by gamma
      scintigraphy. The scintigraphic method is useful for a general description of
      deposition patterns, but may not be adequate for quantitative regional dose
      estimation. New emerging three-dimensional lung imaging methods such as SPECT and
      PET, and innovative bolus aerosol delivery methods, have great potential for
      measuring detailed regional deposition. An accurate assessment of regional lung
      dose is difficult to achieve by the current methods. A multi-prong approach may
      be needed, with various methods and techniques, both in theory and experiment, to
      measure site-specific deposition dose.

PMID- 10894463
TI  - Lung models: strengths and limitations.
AB  - The most widely used particle dosimetry models are those proposed by the National
      Council on Radiation Protection, International Commission for Radiological
      Protection, and the Netherlands National Institute of Public Health and the
      Environment (the RIVM model). Those models have inherent problems that may be
      regarded as serious drawbacks: for example, they are not physiologically
      realistic. They ignore the presence and commensurate effects of naturally
      occurring structural elements of lungs (eg, cartilaginous rings, carinal ridges),
      which have been demonstrated to affect the motion of inhaled air. Most
      importantly, the surface structures have been shown to influence the trajectories
      of inhaled particles transported by air streams. Thus, the model presented herein
      by Martonen et al may be perhaps the most appropriate for human lung dosimetry.
      In its present form, the model's major "strengths" are that it could be used for
      diverse purposes in medical research and practice, including: to target the
      delivery of drugs for diseases of the respiratory tract (eg, cystic fibrosis,
      asthma, bronchogenic carcinoma); to selectively deposit drugs for systemic
      distribution (eg, insulin); to design clinical studies; to interpret scintigraphy
      data from human subject exposures; to determine laboratory conditions for animal
      testing (ie, extrapolation modeling); and to aid in aerosolized drug delivery to
      children (pediatric medicine). Based on our research, we have found very good
      agreement between the predictions of our model and the experimental data of
      Heyder et al, and therefore advocate its use in the clinical arena. In closing,
      we would note that for the simulations reported herein the data entered into our
      computer program were the actual conditions of the Heyder et al experiments.
      However, the deposition model is more versatile and can simulate many aerosol
      therapy scenarios. For example, the core model has many computer subroutines that
      can be enlisted to simulate the effects of aerosol polydispersity, aerosol
      hygroscopicity, patient ventilation, patient lung morphology, patient age, and
      patient airway disease.

PMID- 10894464
TI  - Assessment end points for inhaled drug delivery.
AB  - There is no "best" outcome or "gold standard" in the assessment of inhaled drug
      delivery. All levels of inquiry are important in development of drug formulations
      and delivery devices, and culminate in optimal therapy for the patient. Some
      advantages and disadvantages of each approach are summarized in Table 3. Each
      level forms a framework for the next step in the process, with in vitro leading
      to in vivo, followed by clinical trials. For optimal design, predictions and
      measurements of inhaled drug delivery should be done prior to large, expensive
      clinical trials. Bench testing with in vitro models is essential to document the
      performance of the delivery device/drug combination, whereas in vivo studies
      examine the behavior of the aerosol in human subjects. Both scintigraphy and
      pharmacokinetic/pharmacodynamic studies can add insights into the relationship
      between drug delivery and clinical efficacy and toxicity. There is a need for
      continued investigation on the subject of inhaled drug delivery, including more
      trials that bridge the levels of testing. We need more trials comparing in vitro
      with in vivo outcomes, as well as trials that relate in vivo assessments to
      clinical outcomes. In the final analysis, however, there is no substitute for
      clinical trials in patients. There is a lack of published, well-designed,
      randomized, controlled clinical trials comparing delivery devices or drug
      formulations. For these, attention must be given to the definition of the
      population, the dose-response relationships, and the expression of the
      physiologic responses. It is also important that clinical trials monitor both
      objective and subjective outcomes, as symptoms and quality of life measures help
      quantify the impact of disease and therapy on daily life.

PMID- 10894465
TI  - Assessing costs of aerosol therapy.
AB  - The large economic burden of asthma accentuates the need for economically sound
      treatment. Numerous studies report that the outcomes produced by nebulizers are
      equivalent to the outcomes produced by MDI/spacers in selected patients. Studies
      show that MDI/spacer use will probably result in substantial cost savings to
      hospitals. Although some patients will not be able to achieve the same outcomes
      with MDI/spacers as with nebulizers, Bowton et al and Orens et al showed that a
      large percentage of patients could be converted to the less costly MDI/spacer
      therapy without negative repercussions. Observation of current treatment practice
      indicates that hospitals have yet to capitalize on the economic benefits of
      replacing nebulizers with MDI/spacers. For example, original data from MARC
      indicate that only 5% of adults who present to an academic ED with acute asthma
      receive at least one beta agonist treatment via MDI. Studies that improve upon
      existing cost analyses may convince hospitals of the untapped savings potential.
      Investigation of barriers to MDI/spacer conversion, along with a compilation of
      successful strategies for this conversion, would be helpful. Taken together, such
      research could lead to increased beta agonist delivery via MDI/spacer and
      probable savings to the health care system.

PMID- 10894466
TI  - Aerosolized drugs: current regulatory perspective.
AB  - By understanding the way the regulatory concepts of safety and effectiveness are
      interpreted by CDER, especially by the Division of Pulmonary Drug Products, value
      can be added to the data developed. Keeping regulatory requirements in mind
      during early product development aids rapid evaluation of aerosol drug candidates
      and can lead to more efficient decisions about further development. Health care
      practitioners, the medical research community, and patient advocates can and do
      have a voice in the development of new regulations.

PMID- 10894467
TI  - Aerosol therapy past, present, and future: a clinician's perspective.

PMID- 10894468
TI  - Cloned lines of Babesia bovis differ in their ability to induce cerebral
      babesiosis in cattle.
AB  - Clones of a Babesia bovis isolate known to cause particularly severe cerebral
      babesiosis were tested for virulence phenotype by inoculation of cattle. Clones
      were selected for phenotyping by two criteria - rate of growth in culture and
      hybridization of a virulence-related probe to Southern blots. Largely on the
      basis of associated mortality, B. bovis clones were judged to vary in their
      pathogenic potential.

PMID- 10894469
TI  - Molecular genetic characterization and subcellular localization of Theileria
      annulata mitochondrial heat-shock protein 70.
AB  - A Theileria annulata mitochondrial heat-shock protein of the 70-kDa family
      (Tamthsp70) was isolated by screening of the cDNA library of a T. annulata
      infected bovine lymphoblastoid cell line with an antibody raised against T.
      annulata schizonts. The Tamthsp70 coding sequence was found to be most closely
      related to a previously reported mitochondrial hsp70 gene of Eimeria tenella
      exhibiting a similarity of 67% with mitochondrial hsp70 genes of eukaryotic
      plants (Pisum sativum, Phaseolus vulgaris) and with dnaK proteins of prokaryotes
      (Rhizobium meliloti, Agrobacterium tumefaciens). The Tamthsp70 mRNA is expressed
      within the sporozoite, schizont, and merozoite stages of the parasite, which
      suggests that it is constitutively transcribed throughout the life cycle. The
      gene encodes a polypeptide of 681 amino acids and exhibits a mitochondrial
      targeting sequence and several sequence motifs common to mitochondrial hsp70 and
      prokaryotic dnaK proteins. The protein level of the Tamthsp70 protein after heat
      shock decreased slightly during the exposure of infected cells to a temperature
      of 42 degrees C in comparison with cells cultured at 37 degrees C. By
      immunofluorescence the protein was located in the area in which the schizonts
      reside within infected cells. Immunoelectron microscopy showed that the hsp70
      protein was predominantly localized in the mitochondria of the parasites.
      However, it was also found in small amounts in the cytoplasm of the parasite and
      host cell. This indicates (1) that Tamthsp70 is very probably translated in the
      parasite cytoplasm and then transported across the mitochondrial membrane into
      the mitochondrial matrix and (2) that it is transported across the parasite
      membrane into the host-cell cytoplasm.

PMID- 10894470
TI  - Localization and immunogenicity of a low molecular weight antigen of Eimeria
      tenella.
AB  - A low molecular weight (LMW) antigen recognized by a murine monoclonal antibody
      (C(3)4F(1)) was localized within endogenous stages of Eimeria tenella (USDA
      strain 80). Using indirect fluorescent antibody assay and immunoelectron
      microscopy, the LMW antigen was found in: sporozoites, first, second and third
      generation meronts, gamonts, unsporulated oocysts, and sporocysts. The antigen
      was observed in the cytoplasm and pellicle of the parasite, and in the
      parasitophorous vacuole, sporocyst walls and cytoplasm of infected host cells.
      The immunogenicity of this LMW antigen was assessed by antigen-specific serum
      antibody responses in chickens orally inoculated with live oocysts or injected
      intramuscularly with dead sporozoites. LMW antigen-specific serum antibodies were
      detected using Western blots of E. tenella sporozoites as early as 4 days after
      sporozoite injection and 6 days after oocyst inoculation. Unusually, the
      monoclonal antibody C(3)4F(1) reduced the binding of immune chicken serum to the
      antigen in a competitive antibody binding assay, but not the reverse, suggesting
      that there is a single, immunodominant epitope on this antigen.

PMID- 10894471
TI  - Partial characterization of a non-proteinaceous, low molecular weight antigen of
      Eimeria tenella.
AB  - A low molecular weight (LMW) antigen of Eimeria tenella, initially identified
      using a murine monoclonal antibody (mAb C(3)4F(1)) raised against E. tenella
      sporozoites, was partially characterized using enzymatic degradation. solvent
      extraction, and immunization into various inbred lines of mice. The LMW antigen
      could be isolated using Folch extraction (methanol/chloroform/ water) and the
      epitope recognized by mAb C(3)4F(1) was resistant to degradation by alpha
      amylase, pronase, and proteinase K, but was sensitive to sodium m-periodate
      treatment or digestion using mixed glycosidases (from Turbo cornutus). These
      observations suggest that the antigenic epitope recognized by mAb C(3)4F(1) is
      carbohydrate-dependent and, based on our ability to isolate the LMW antigen by
      Folch extraction, the epitope probably resides on a polar glycolipid. The
      inability of sporozoite-immunized nude mice to elicit a serum antibody response
      to this molecule indicates that it acts as a T-dependent antigen. Furthermore,
      sporozoite-immunized male CBA/N mice (with an X-linked immunodeficiency) also
      failed to elicit a serum antibody response to this molecule, which is consistent
      with a carbohydrate antigenic epitope. We propose that this antigenic molecule be
      designated ET-GL1 to reflect its origin and probable structure (E. tenella
      glycolipid 1).

PMID- 10894472
TI  - Ultrastructure studies on post-oocyst development of the lizard hemogregarine
      Hemolivia mariae in the tick Amblyomma limbatum.
AB  - The ultrastructural features of the development of Hemolivia mariae, a blood
      parasite of the Australian lizard, Tiliqua rugosa, from sporokinetes to
      sporozoites in their vector tick Amblyomma limbatum are described. Sporokinetes,
      released from oocysts, re-establish themselves in tick-gut epithelial cells
      within a parasitophorous vacuole, the wall of which becomes evaginating and
      anastomosing and is underlined extensively by endoplasmic reticulum. The
      sporozoites forming within the encysting sporokinete body become bordered by a
      prominent thick wall, which eventually forms the resistant sporocyst wall. The
      main differences between the ultrastructural features of Hemolivia and those of
      other hemogregarine taxa are discussed.

PMID- 10894473
TI  - IgG antibody response to ES or somatic antigens of Dicrocoelium dendriticum
      (Trematoda) in experimentally infected sheep.
AB  - The ELISA technique was used to study the kinetics of IgG antibodies against
      excretory-secretory (ES) and somatic (So) antigens of Dicrocoelium dendriticum in
      the sera of 32 lambs: 12 experimentally infected with 1,000 metacercariae, 12
      with 3,000 and 8 controls. Both antigen types were used at a 2 microg/ml
      concentration. Dilutions of sera and the anti-sheep IgG peroxidase conjugate
      were: 1:200 and 1:6,000, respectively. Optical density values for each type of
      antigen in the two infected groups were higher than the cut-off point from day 30
      post infection (p.i.), showing positive infection. Maximum antibody levels were
      observed 60 days p.i. and remained high until the experiment ended 180 days p.i.
      This pattern was similar for both ES and So antigens, although with slightly
      lower figures in the latter. Antibody kinetics were very similar for each of the
      two doses, except on day 30 p.i. No correlation between the antibody level and
      parasite burden could be established.

PMID- 10894474
TI  - Inhibition of the protective IgA response by ketotifen is related to the
      inflammatory reaction in the peritoneal cavity and intestinal mucosa of BALB/c
      mice infected with Trichinella spiralis.
AB  - Interleukin-5 (IL-5) production, eosinophilia, and IgA responses of BALB/c mice
      infected with Trichinella spiralis were measured in the peritoneal cavity and
      intestinal mucosa. Ketotifen, an anti-allergic compound, was used to control the
      inflammatory response. IgA responses differed against adult and muscle stages of
      the parasite and between the intestine and the peritoneal cavity. IL-5 and
      eosinophil production also differed between the intestine and the peritoneal
      cavity. The occurrence of parasite-specific IgA antibodies in the peritoneal
      cavity may reflect the migration of cells from the lamina propria. Following
      ketotifen treatment there was a reduction in the IL-5, eosinophilic, and IgA
      responses; these responses affected both the size of worms and the number of
      worms.

PMID- 10894475
TI  - The sexually linked Mpi locus is presumably involved in imidothiazole resistance
      in Oesophagostomum dentatum parasites.
AB  - Information about genetic changes during the selection process could indicate
      mechanisms underlying the spread of resistance to anthelmintic drugs. For
      clarification of the role of the Mpi locus encoding mannose-phosphate isomerase
      enzyme in determining resistance, genotyping of Oesophagostomum dentatum strains
      was performed using an isoelectrofocusing technique. In levamisole- and pyrantel
      selected strains the allele associated with resistance has probably been found.
      Significant values for genetic differentiation between treated and untreated
      strains of common origin were recorded by F(st) indices (theta = 0.078; P =
      0.0008). The specific genomic makeup of a flubendazole-resistant strain, which
      did not correlate with that of the remaining isolates, might be ascribed to a
      different action of the anthelmintic or different environmental conditions under
      which resistance against this drug arose. The absence of heterozygotes in male
      populations indicated an XX/X0 system of sex determination for the Mpi locus,
      thus providing a greater potential for the development of resistance. A possible
      involvement of alleles linked with mannose-phosphate isomerase in alterations of
      membrane receptors that can be associated with resistance against imidothiazole
      based drugs is discussed.

PMID- 10894476
TI  - Cytokines (IL-4 and IFN-gamma) and antibodies (IgE and IgG2a) produced in mice
      infected with Borrelia burgdorferi sensu stricto via nymphs of Ixodes ricinus
      ticks or syringe inoculations.
AB  - Mice were tolerant to tick bites during three infestations with nymphs of Ixodes
      ricinus infected with Borrelia burgdorferi sensu stricto. To determine whether
      tick bites influence the immune response against B. burgdorferi, we examined the
      production of cytokines IL-4 and IFN-gamma by lymph node cells of BALB/c mice and
      IL-4 deficient BALB/c mice after tick inoculation versus syringe inoculation of
      B. burgdorferi. We also measured IgG2a anti-borrelial antibodies and total IgE in
      these mice. Results showed that BALB/c mice developed a Th2 immune response
      against B. burgdorferi after tick inoculation and a mixed Th1/Th2 response after
      syringe inoculation of B. burgdorferi. IL-4 deficient mice produced a Th1 immune
      response in both cases. IL-4 produced following tick bites greatly decreased the
      production of anti-borrelial IgG2a antibodies by comparison with the production
      of anti-borrelial IgG2a antibodies produced following syringe injection of B.
      burgdorferi.

PMID- 10894477
TI  - Unusual organization of the 5S ribosomal spacer in Dirofilaria repens: absence of
      a canonical spliced leader 1 sequence.
AB  - Comparing the 5S ribosomal RNA spacer of Dirofilaria repens and D. immitis, we
      found that in D. repens PCR generates two amplification products. In both
      products, the putative spliced leader 1 sequences (SL1) show some nucleotide
      substitutions compared to the canonical SL1 sequence of nematodes. SL I is a
      short sequence transferred to the 5' end of most messenger RNAs through a trans
      splicing reaction. All the other filariae studied thus far amplify a single
      fragment showing a canonical SL1 sequence. D. repens appears thus peculiar.

PMID- 10894478
TI  - Cellular immune responses in human neurocysticercosis.
AB  - Studies on the role of cell-mediated immune responses in human neurocysticercosis
      (NCC) are lacking. Various cell-mediated immune responses such as lymphocyte
      subpopulation, lymphocyte transformation to cysticercus antigens and cytokine
      profile were carried out in NCC patients. Lymphocyte transformation assays using
      larval antigens showed significantly higher (3)H-thymidine uptake.
      Immunophenotyping analysis showed an insignificant increase in B cells and a
      decrease in total T cells. However, there was a significant decrease (P < 0.05)
      in CD8+ T cells whereas there was no change in other cells like CD4+, HLA-DR+ and
      CD16+/CD56+. Cytokine profile revealed significantly higher (P < 0.01) production
      of Th1 cytokines (gamma-IFN and IL-2) using cysticercal antigens as stimulants
      for peripheral blood mononuclear cells, while there was no difference in IL-4
      levels between NCC patients and healthy controls. The cytokine profile indicated
      the involvement of Th-1-like responses in NCC patients.

PMID- 10894479
TI  - Molecular and biologic characterization of Leishmania parasites implicated in an
      epidemic outbreak in northwestern Argentina.
AB  - Leishmania (Viannia) braziliensis and its variants were implicated in the
      epidemic outbreak of mucocutaneous leishmaniasis that occurred in Salta,
      northwestern Argentina, in 1985. A total of 24 suspected, untreated cases were
      evaluated clinically and parasitologically. Four of five stable isolates were
      consistent with the reference strain of L. (V.) braziliensis as determined by
      monoclonal antibodies and indirect immunofluorescence or radioimmunobinding
      assays. Zymodeme analysis in agarose gels showed a close relationship with L.
      (V.) guyanensis and L. (V.) panamensis. All zymograms obtained with
      polyacrylamide gels belonged to the subgenus Viannia; the patterns were different
      from, but very closely related to, the reference strains of L. (V.) braziliensis
      as determined by dendrogram analysis. Hamsters infected with two isolates showed
      a pattern consistent with L. (V.) braziliensis. The pattern of development in the
      gut of Lutzomyia longipalpis was consistent with members of Viannia.

PMID- 10894480
TI  - Experimental cysticercosis and the intrahepatic venous systems in Rattus
      norvegicus.
AB  - During the present investigation, alterations in the intrahepatic venous and
      portal systems in Rattus norvegicus infected with 250, 500, and 1000 Taenia
      taeniaeformis eggs were studied. The corrosion cast technique was employed, which
      provides an extrinsic opportunity for study of the three-dimensional orientation
      of the vascular architecture. Both of the venous trees were found to be affected,
      though the portal damage was more extensive. Maximal damage was inferred at 40
      days post-infection, when the normal regularity of ramification was lost.
      Concisely, cysticercosis induced severe changes in the intrahepatic vascular
      systems, which were found to have gradually recovered at the later stages of
      infection.

PMID- 10894481
TI  - Vannella sp. harboring Microsporidia-like organisms isolated from the contact
      lens and inflamed eye of a female keratitis patient.
AB  - Viable Hartmannella sp. and two strains of Vannella sp.--but no Acanthamoebae-
      multiplied on NN-agar inoculated with pieces of the contact lens from a female
      keratitis patient. Within the cytoplasm of one Vannella isolate, intracellular
      parasites could be observed whose earliest stages were developing within the
      nucleus, resembling those Microsporidia-like parasites seen within Vannella
      isolated recently from a warm tapwater system. This assumption was also confirmed
      by electron microscopy. In swabs taken directly from the cornea, Pseudomonas
      aeruginosa were identified, but they did not yield any growth of amebas in
      culture. However, cocultivation of parasite-free Vannella strains with the above
      mentioned swab matter resulted in infected amebas harboring the same
      intracellular parasites seen before. This infection could be established only if
      the corresponding spores were present as infective agents in the swab matter. The
      successful treatment of the patient with antibiotics supports the assumption that
      P. aeruginosa was the main cause of the corneal ulceration. The extent to which
      the Microsporidia-like organisms may have been involved in the development of
      keratitis remains a matter of discussion.

PMID- 10894483
TI  - Copulation of Acanthocephalus anguillae (Acanthocephala).
AB  - A total of 114 specimens of brown trout, Salmo trutta Linnaeus, 1758, was sampled
      by electrofishing between October 1998 and July 1999 from the Ceresone stream
      (North of Padua, Italy). Over 63% of fish were infected with three species of
      helminth: a tapeworm, Cyathocephalus truncatus (Pallas, 1781), and two
      acanthocephalan species, Echinorhynchus truttae (Schrank, 1788) and
      Acanthocephalus anguillae (Muller 1780). On three occasions, in the fore-gut of
      three brown trout, three pairs of A. anguillae were found in copula. In all three
      cases, the male's bursa was fully extruded and firmly attached to the posterior
      region of the female. Cement was found inside the bursa suggesting that
      insemination had probably occurred. Eight female A. anguillae recovered in five
      other infected trout had attached copulatory caps.

PMID- 10894482
TI  - Dose dependency of prednisolone tertiary-butylacetate (PTBA) treatment on the
      establishment and site predilection of Echinococcus multilocularis in an
      alternative definitive host model using Mongolian gerbil (Meriones unguiculatus).
AB  - Mongolian gerbils (Meriones unguiculatus) were orally inoculated with 10,000
      protoscoleces of Echinococcus multilocularis per head after being divided into
      five groups (A E). Each group was dosed with prednisolone tertiary-butylacetate
      (PTBA) as follows: A, 0 mg; B, 0.5 mg; C, 2 mg; D, 5 mg; and E, 10 mg/head. All
      animals were injected subcutaneously with control solvent or PTBA every other day
      from 6 days pre- to 6 days post-infection. Autopsy was performed at 7 days post
      infection. Doses of PTBA and the number of worms recovered showed a positive
      correlation (r = 0.929, P < 0.0001). In groups A, B and C, the predilection site
      of the worms in the small intestine could not be determined, while in group D the
      worms were found more in the anterior part. In group E, the predilection site was
      the anterior part, followed by the middle and the posterior parts of the small
      intestine (Fisher's test: P < 0.01). The number of worms recovered from the
      anterior and the middle part of the small intestine also correlated positively
      with PTBA dose (anterior part: r = 0.930, P < 0.0001, middle part: r = 0.917, P <
      0.0001). All groups of the PTBA-treated animals showed significant loss of weight
      compared to the nontreated animals (P < 0.01).

PMID- 10894484
TI  - Findings of Fasciola hepatica Linnaeus, 1758 in wild animals in Belorussian
      Polesie.

PMID- 10894485
TI  - Helminth fauna of otter (Lutra lutra Linnaeus, 1758) in Belorussian Polesie.

PMID- 10894486
TI  - Reporting pain and distress.

PMID- 10894487
TI  - Using antibiotics responsibly.

PMID- 10894488
TI  - False negative results using RT-PCR for detection of lactate dehydrogenase
      elevating virus in a tumor cell line.

PMID- 10894489
TI  - Intranasal vaccination of New Zealand white rabbits against pasteurellosis, using
      alginate-encapsulated Pasteurella multocida toxin and potassium thiocyanate
      extract.
AB  - OBJECTIVE: We evaluated the efficacy of intranasal administration of Pasteurella
      multocida toxin (PMT) and a potassium thiocyanate extract of P. multocida (CN)
      encapsulated in alginate microspheres, compared with unencapsulated PMT and CN
      antigens, in protection of rabbits against pasteurellosis. METHODS: New Zealand
      male rabbits (n=24) were allotted randomly into four intranasally administered
      vaccine groups: 1, PMT/CN; 2, microencapsulated PMT/CN with or; 3, without
      subcutaneous priming; and 4, empty microspheres (control). Blood samples and
      nasal wash specimens were collected before vaccination and one week after each
      vaccination (days 7, 21, 35, and 49). Rabbits were primed subcutaneously with
      either unencapsulated PMT/CN or aluminum hydroxide (control) (day 0), vaccinated
      intranasally (days 14, 28, and 42), challenged intranasally with live P.
      multocida (day 56), and necropsied (day 60). RESULTS: Compared with controls,
      PMT/CN-immunized rabbits had significantly higher concentrations of serum IgG and
      IgM, nasal IgG, and bronchoalveolar lavage fluid IgA and IgG against CN.
      Immunized rabbits had 100% survival rate and low numbers of bacteria in liver and
      lungs; the control group had 50% survival rate and higher numbers of bacteria (>
      4x) per gram of tissue in liver and lungs. CONCLUSION: The PMT/CN microspheres
      stimulated systemic and mucosal immune responses similar in effectiveness
      (protection) to those in response to unencapsulated PMT/CN administration.

PMID- 10894490
TI  - Protection from Cryptosporidium parvum infection by gammadelta T cells in mice
      that lack alphabeta T cells.
AB  - BACKGROUND AND PURPOSE: Cryptosporidium parvum establishes a parasitic
      relationship with epithelial cells of the intestine. Infection with this
      protozoan is resolved in the immunocompetent host, but persistent life
      threatening infection develops in the immunocompromised host. We propose that
      gammdelta T cells in the intestinal mucosa play a role in immunity to C. parvum.
      METHODS: Intestinal intra-epithelial lymphocyte and lamina propria T-cell subsets
      were examined in mice infected with C. parvum. The mice are homozygous for a
      deletion of the TCRalpha chain gene, TCRalpha(-/-) and, therefore, lack
      conventional alphabeta T cells, but retain a population of T cells with
      gammadelta T-cell receptors. To examine the contribution of gammadelta T cells to
      immunity, these mice were treated with monoclonal antibody GL3-3A, specific for
      this T-cell receptor, then were inoculated with C. parvum oocysts. Lymphocyte
      subsets and hematoxylin and eosin (H&E)-stained intestinal sections from
      untreated mice were compared with those from mice treated with either a low dose
      of GL3-3A for 6 weeks, or a high dose of GL3-3A for 16 weeks. RESULTS: The
      proportion of gammadelta T cells in the lamina propria increased in infected
      mice. In mice treated with a low dose of GL3-3A, a population of gammadelta T
      cells that had characteristics of activated cells, was still evident 6 weeks
      after inoculation. No C. parvum developmental forms were identified in the
      intestinal sections of mice under these conditions. However, TCRalpha(-/-) mice
      treated with a high dose of GL3-3A were depleted of gammadelta T cells, and 50%
      of the mice were infected with C. parvum. CONCLUSIONS: The gammadelta T cells
      contribute to protection against C. parvum infection. In the absence of
      conventional T cells, activation of intestinal gammadelta T cells may prevent
      infection with this organism.

PMID- 10894491
TI  - Changes in plasma arginine vasopressin concentration during lactation in rats.
AB  - BACKGROUND AND PURPOSE: The objectives of the study reported here were to
      determine whether a change in the plasma arginine vasopressin (AVP) concentration
      occurred in lactating, compared with non-lactating rats and to examine the
      involvement of suckling with plasma AVP concentration. METHODS: Experiments were
      performed on 86 female Wister Imamichi rats, 12 weeks old at parturition, with
      fast lactation. On day 13 of lactation, AVP concentration and plasma osmotic
      pressure were measured in lactating and non-lactating rats. RESULTS: Plasma AVP
      concentration was always higher in rats of the lactating groups than in non
      lactating controls (1.06 +/- 0.28 pg/ml), and a conspicuous increase in AVP
      concentration was seen during the postsuckling period (1.70-0.61 pg/ml before vs.
      2.56 +/- 1.31 pg/ml after suckling, P < 0.05). Plasma osmotic pressure in
      lactating rats with 12 pups (296.6 +/- 5.2 mOsmol/kg x H2O) was lower than that
      in rats of the removed control groups (306.7 +/- 5.7 mOsmol/kg x H2O).
      CONCLUSION: On the basis of these results, it appears that "low plasma osmotic
      pressure-high AVP status" develops in the lactating period, similar to pregnancy,
      through resetting of the regulatory mechanism of the AVP system. It was concluded
      that suckling stimulation could release AVP, which could dilute the blood with
      water resulting in the increase in circulating blood volume.

PMID- 10894492
TI  - Selective breeding of house musk shrew (Suncus murinus) lines in relation to
      emesis induced by veratrine sulfate.

PMID- 10894493
TI  - Genital tract development in peripubertal female CD IGS rats.

PMID- 10894494
TI  - Immunologic variables in male and female C57BL/6 mice from two sources.

PMID- 10894495
TI  - Effect of anesthetics on pathogenesis of experimentally induced murine
      pneumococcal pneumonia.
AB  - BACKGROUND AND PURPOSE: To define the effects of three commonly used anesthetic
      agents--sodium pentobarbital given intraperitoneally, and inhaled halothane and
      methoxyflurane--on the pathogenesis of pneumococcal pneumonia and bacteremia in
      an experimental murine model. METHODS: Swiss outbred mice were anesthetized with
      either sodium pentobarbital, halothane, or methoxyflurane before intranasal
      infection with Streptococcus pneumonia. At defined times after infection,
      bacterial numbers in lungs and blood, markers of acute lung injury, and lung
      cytokine levels were compared. RESULTS: Mice anesthetized with inhaled halothane
      or methoxyflurane prior to intranasal inoculation with type-2 Streptococcus
      pneumoniae developed pneumonia and bacteremia distinctly different from that in
      mice anesthetized by intraperitoneal (IP) administration of sodium pentobarbital.
      Mice having brief exposure to inhaled halothane or methoxyflurane had
      significantly greater numbers of bacteria in lungs and blood 48 hours after
      inoculation, compared with mice anesthetized by IP administration of
      pentobarbital. Also, mice inhaling halothane had significantly decreased
      activities of pro-inflammatory cytokines interleukin 6 and tumor necrosis factor
      alpha in lung homogenates at 24 hours after inoculation, compared with those
      given pentobarbital IP. CONCLUSION: Effects of anesthesia on murine models of
      pneumonia should be considered in the design and interpretation of studies of
      pneumococcal pathogenesis.

PMID- 10894496
TI  - Identification of two chromosomal loci determining glucose intolerance in a
      C57BL/6 mouse strain.
AB  - BACKGROUND AND PURPOSE: Our objective was to map the genes responsible for poor
      glucose tolerance in a C57BL/6 (B6) mouse model, which provides a human model of
      non-insulin-dependent diabetes mellitus. Insulin secretion was found to be
      significantly lower in B6 than in C3H/He (C3H) mice (analysis of variance, P <
      0.05) at 10, 20, and 30 minutes during the intraperitoneal glucose tolerance test
      (IPGTT: 1.5 g glucose/kg of body weight). METHODS: Mean 30-minute blood glucose
      values during IPGTT at 8, 9, and 10 weeks of age were used as a surrogate for
      glucose tolerance. The primers of 87 genetic microsatellite markers (14.9 +/- 6.2
      cM apart) genome-wide quantitative trait linkage (QTL) analysis in F2 and F3 mice
      with the highest and lowest (n = 15 for each extreme) 30-minute blood glucose
      values were used. RESULTS: Genome-wide QTL analysis confirmed the locus (D2Mit48)
      on chromosome 2, with a LOD score of 8.3, and the locus (D13Mit48) on chromosome
      13, with a LOD score of 4.2 in F3. Direct sequencing of candidate genes,
      proprotein convertase-2 (PC2) on chromosome 2 and proprotein convertase-1/3
      (PC1/PC3) on chromosome 13, failed to reveal a mutation or polymorphism specific
      to B6 mice. CONCLUSIONS: Use of QTL mapping revealed two loci associated with
      poor glucose tolerance of B6.

PMID- 10894497
TI  - Cardiovascular responses to propofol and etomidate in long-term instrumented
      rhesus monkeys (Macaca mulatta).
AB  - BACKGROUND AND PURPOSE: Cardiac and arterial responses to prescribed doses of
      propofol and etomidate in rhesus monkeys were compared. METHODS: Intravenously
      administered induction doses of propofol (2 mg/kg of body weight) or etomidate (1
      mg/kg) followed by continuous intravenous infusions of propofol (200
      microg/kg/min) or etomidate (100 microg/kg/min) were administered. Left
      ventricular and right atrial access catheters were implanted for long-term use,
      along with a transit-time flow probe on the ascending aorta, and pericardial
      electrocardiogram leads. A dual sensor 3-F micromanometer was used to measure
      left ventricular pressure and aortic pressure, and an active redirectional
      transit-time probe measured aortic flow. Noordergraaf's four-element model was
      used to estimate total peripheral resistance and systemic arterial compliance.
      RESULTS: Significant (P < 0.01) decreases in mean arterial pressure, heart rate,
      and myocardial contractility were accompanied by an increase in systemic arterial
      compliance associated with propofol and etomidate. Only minimal changes in left
      ventricular diastolic pressure, cardiac output, stroke volume, and total
      peripheral resistance were found for both drugs. The changes associated with
      propofol are comparable to results in human beings, whereas the changes
      associated with etomidate did not agree with results of published human studies.
      CONCLUSION: The significant cardiovascular alterations associated with both
      agents were attributed to reductions in heart rate, although the possibility
      exists that negative inotropic effects may have had a role.

PMID- 10894498
TI  - Measurement of rabbit apolipoprotein B by use of electroimmunodiffusion and
      immunonephelometric assays.
AB  - BACKGROUND AND PURPOSE: Because of their similarity to humans, rabbits are a good
      animal model for the study of atherosclerosis associated with high serum low
      density lipoprotein (LDL) values. Two assays were developed to measure
      apolipoprotein B (apoB), the major structural and functional apolipoprotein of
      LDL in rabbits and to distinguish endogenous LDL in transgenic rabbits from that
      of human apoB. METHODS: Two procedures, an electroimmunoassay (EIA) and an
      immunonephelometric assay (INA), along with a goat-origin rabbit antiserum were
      developed to measure serum apoB concentration in rabbits. RESULTS: Use of either
      assay resulted in ability to measure rabbit species-specific apoB concentration.
      CONCLUSION: These assays should have broad applications: to screen compounds or
      diets that might lower serum apoB concentrations; to specifically measure human
      apoB concentration in transgenic rabbits; to measure serum apoB concentration in
      rabbits overexpressing other human proteins.

PMID- 10894499
TI  - Deoxyribonucleic acid preparation in polymerase chain reaction genotyping of
      transgenic mice.
AB  - BACKGROUND AND PURPOSE: In an attempt to find a rapid and reproducible method for
      routine polymerase chain reaction genotyping of transgenic mice, two novel
      approaches were developed. METHODS: One approach allowed reproducible
      amplification from crude lysates of tail snips, using a thermally activated
      polymerase. In a second approach, for situations in which non-invasive techniques
      are necessary, oral swab specimens were amplified after DNA extraction by use of
      an isolation kit. Samples from 10 transgenic factor VIII knockout mice were
      genotyped after processing by use of these and other methods. RESULTS: False
      negative results were not obtained by use of the two novel approaches. Despite
      their relative simplicity, both approaches yielded results comparable to those
      obtained by use of procedures known to be reliable, such as organic extraction
      and a DNA extraction kit. CONCLUSION: Both approaches are useful for PCR
      amplification of DNA from mammalian sources.

PMID- 10894500
TI  - Herpes B-virus specific-pathogen-free breeding colonies of macaques (Macaca
      mulatta): diagnostic testing before and after elimination of the infection.
AB  - BACKGROUND AND PURPOSE: The National Institutes of Health's (NIH) National Center
      for Research Resources' (NCRR) Division of Comparative Medicine has funded the
      establishment of specific pathogen-free (SPF) captive macaque colonies. Herpes B
      virus (Herpesvirus simiae, Cercopithecine herpesvirus type 1) has been targeted
      for elimination. Late seroconversion presents the greatest threat to the
      integrity of SPF colonies. The purpose of the study reported here was to evaluate
      that threat through detailed investigation of the patterns of seroreactivity and
      housing histories in one colony. METHODS: From 1990 through 1997, the B-virus
      Resource Laboratory screened macaques for B-virus, using ELISA or western
      immunoblot analysis. In 1993, we combined test results and housing histories to
      verify the seronegative status of one colony. RESULTS: Two groups of latently
      infected macaques were identified as to time and place of transmission. The
      infection was eradicated within 3 years (1990-1992), as judged by the absence of
      true positive seroreactivity in any screened macaques. New infections were not
      identified in four years of follow-up evaluation. CONCLUSION: With rigorous
      surveillance, the SPF status of the colony was achieved and maintained.

PMID- 10894501
TI  - Granulomatous pneumonia in the opossum (Didelphis virginiana) associated with an
      intracellular fungal agent.
AB  - BACKGROUND AND PURPOSE: Two of nine female opossums (Didelphis virginiana) in a
      closed breeding colony were submitted for necropsy due to a history of poor
      reproductive performance in the absence of overt clinical disease. On histologic
      examination, marked granulomatous to pyogranulomatous pneumonia was identified in
      these animals. METHODS: Lung sections were stained with periodic acid-Schiff and
      Gomori's methenamine silver nitrate. RESULTS: Pulmonary lesions were
      characterized by large numbers of foamy macrophages within the alveoli and
      interstitium, prominent subpleural and peribronchiolar aggregates of histiocytes,
      and a few scattered lymphoid nodules. Numerous fungal organisms were evident
      within the cytoplasm of macrophages on impregnation of histologic sections with
      the aforementioned stains. Other inciting agents were not identified. A third
      opossum lacked pulmonary lesions, but had similar organisms within one auricular
      sebaceous gland/hair follicle without apparent reaction to the organisms.
      CONCLUSION: A fungal agent was associated with granulomatous pneumonia in the
      opossum, and comparison was made with endogenous lipid pneumonia previously
      described in opossums. These findings stress the importance of use of special
      stains and additional diagnostic techniques when prominent alveolar macrophage
      accumulation is present on histologic examination of the opossum lung.

PMID- 10894503
TI  - Los Alamos deserves better

PMID- 10894502
TI  - Confounding influences on phenotype expression in MRL/lpr mice.

PMID- 10894504
TI  - Declaration for AIDS sufferers.

PMID- 10894505
TI  - African scientists join colleagues in affirming HIV's role in AIDS...but advisory
      panel remains divided.

PMID- 10894507
TI  - Study compares chimps and people.

PMID- 10894506
TI  - Royal society warns on hormone disrupters.

PMID- 10894508
TI  - NIH urged to cap profits made on publicly funded research.

PMID- 10894509
TI  - Indian space agency sets its sights on a mission to the Moon

PMID- 10894510
TI  - Good news for German genome research...but proposed panel may hamper Italian gene
      researchers.

PMID- 10894512
TI  - Austrian physics meeting passes without boycott

PMID- 10894511
TI  - Self-policing backed for research on humans.

PMID- 10894513
TI  - New law threatens to undermine genetics in New Zealand.

PMID- 10894515
TI  - Astronomers fight to save telescope

PMID- 10894514
TI  - Galileo set for suicide flight

PMID- 10894516
TI  - Will souped up salmon sink or swim?

PMID- 10894517
TI  - How can we build a 'knowledge economy' if research is handcuffed?

PMID- 10894518
TI  - Climate-change analysis has been changing too.

PMID- 10894519
TI  - Unrealistic promises on AIDS fuel scepticism.

PMID- 10894520
TI  - The Durban Declaration.

PMID- 10894521
TI  - Epistemology engines.

PMID- 10894522
TI  - The abdication of Pope Mary III...or Galileo's revenge

PMID- 10894523
TI  - Schrodinger's cat is now fat

PMID- 10894524
TI  - Signal transduction. A cellular rescue team.

PMID- 10894525
TI  - Why trapped atoms are attractive

PMID- 10894526
TI  - Plant biology. An unbearable beating by light?

PMID- 10894527
TI  - Aquatic ecology. Phosphorus, the staff of life.

PMID- 10894528
TI  - Parasites take control.

PMID- 10894529
TI  - Detection of preinvasive cancer cells.

PMID- 10894530
TI  - Degradation of plant cell walls by a nematode.

PMID- 10894531
TI  - Phosphite oxidation by sulphate reduction.

PMID- 10894532
TI  - Inspiration for optimization from social insect behaviour.
AB  - Research in social insect behaviour has provided computer scientists with
      powerful methods for designing distributed control and optimization algorithms.
      These techniques are being applied successfully to a variety of scientific and
      engineering problems. In addition to achieving good performance on a wide
      spectrum of 'static' problems, such techniques tend to exhibit a high degree of
      flexibility and robustness in a dynamic environment.

PMID- 10894533
TI  - Quantum superposition of distinct macroscopic states
AB  - In 1935, Schrodinger attempted to demonstrate the limitations of quantum
      mechanics using a thought experiment in which a cat is put in a quantum
      superposition of alive and dead states. The idea remained an academic curiosity
      until the 1980s when it was proposed that, under suitable conditions, a
      macroscopic object with many microscopic degrees of freedom could behave quantum
      mechanically, provided that it was sufficiently decoupled from its environment.
      Although much progress has been made in demonstrating the macroscopic quantum
      behaviour of various systems such as superconductors, nanoscale magnets, laser
      cooled trapped ions, photons in a microwave cavity and C60 molecules, there has
      been no experimental demonstration of a quantum superposition of truly
      macroscopically distinct states. Here we present experimental evidence that a
      superconducting quantum interference device (SQUID) can be put into a
      superposition of two magnetic-flux states: one corresponding to a few
      microamperes of current flowing clockwise, the other corresponding to the same
      amount of current flowing anticlockwise.

PMID- 10894534
TI  - Generation and detection of phase-coherent current-driven magnons in magnetic
      multilayers
AB  - The magnetic state of a ferromagnet can affect the electrical transport
      properties of the material; for example, the relative orientation of the magnetic
      moments in magnetic multilayers underlies the phenomenon of giant
      magnetoresistance. The inverse effect--in which a large electrical current
      density can perturb the magnetic state of a multilayer--has been predicted and
      observed experimentally with point contacts and lithographically patterned
      samples. Some of these observations were taken as indirect evidence for current
      induced excitation of spin waves, or 'magnons'. Here we probe directly the high
      frequency behaviour and partial phase coherence of such current-induced
      excitations, by externally irradiating a point contact with microwaves. We
      determine the magnon spectrum and investigate how the magnon frequency and
      amplitude vary with the exciting current. Our observations support the
      feasibility of a spin-wave maser' or 'SWASER' (spin-wave amplification by
      stimulated emission of radiation).

PMID- 10894535
TI  - Self-directed growth of molecular nanostructures on silicon
AB  - Advances in techniques for the nanoscale manipulation of matter are important for
      the realization of molecule-based miniature devices with new or advanced
      functions. A particularly promising approach involves the construction of hybrid
      organic-molecule/silicon devices. But challenges remain--both in the formation of
      nanostructures that will constitute the active parts of future devices, and in
      the construction of commensurately small connecting wires. Atom-by-atom crafting
      of structures with scanning tunnelling microscopes, although essential to
      fundamental advances, is too slow for any practical fabrication process; self
      assembly approaches may permit rapid fabrication, but lack the ability to control
      growth location and shape. Furthermore, molecular diffusion on silicon is greatly
      inhibited, thereby presenting a problem for self-assembly techniques. Here we
      report an approach for fabricating nanoscale organic structures on silicon
      surfaces, employing minimal intervention by the tip of a scanning tunnelling
      microscope and a spontaneous self-directed chemical growth process. We
      demonstrate growth of straight molecular styrene lines--each composed of many
      organic molecules--and the crystalline silicon substrate determines both the
      orientation of the lines and the molecular spacing within these lines. This
      process should, in principle, allow parallel fabrication of identical complex
      functional structures.

PMID- 10894536
TI  - Direct measurement of hole transport dynamics in DNA.
AB  - Our understanding of oxidative damage to double helical DNA and the design of DNA
      based devices for molecular electronics is crucially dependent upon elucidation
      of the mechanism and dynamics of electron and hole transport in DNA. Electrons
      and holes can migrate from the locus of formation to trap sites, and such
      migration can occur through either a single-step "superexchange" mechanism or a
      multistep charge transport "hopping" mechanism. The rates of single-step charge
      separation and charge recombination processes are found to decrease rapidly with
      increasing transfer distances, whereas multistep hole transport processes are
      only weakly distance dependent. However, the dynamics of hole transport has not
      yet been directly determined. Here we report spectroscopic measurements of
      photoinduced electron transfer in synthetic DNA that yield rate constants of
      approximately 5 x 10(7) s(-1) and 5 x 10(6) s(-1), respectively, for the forward
      and return hole transport from a single guanine base to a double guanine base
      step across a single adenine. These rates are faster than processes leading to
      strand cleavage, such as the reaction of guanine cation radical with water, thus
      permitting holes to migrate over long distances in DNA. However, they are too
      slow to compete with charge recombination in contact ion pairs, a process which
      protects DNA from photochemical damage.

PMID- 10894537
TI  - Phosphate concentrations in lakes.
AB  - Phosphate is an important nutrient that restricts microbial production in many
      freshwater and marine environments. The actual concentration of phosphate in
      phosphorus-limited waters is largely unknown because commonly used chemical and
      radiochemical techniques overestimate the concentration. Here, using a new steady
      state radiobioassay to survey a diverse set of lakes, we report phosphate
      concentrations in lakes that are orders of magnitude lower than estimates made
      spectrophotometrically or with the frequently used Rigler radiobioassay. Our
      results, combined with those from the literature, indicate that microbes can
      achieve rapid turnover rates at picomolar nutrient concentrations. This occurs
      even though these concentrations are about two orders of magnitude below the
      level where phosphate uptake is estimated to be half the saturation level for the
      pico-plankton community. Also, while phosphate concentration increased with the
      concentration of total phosphorus and soluble reactive phosphorus in the lakes we
      sampled, the proportion of phosphate in the total phosphorus pool decreased from
      oligotrophic to eutrophic lakes. Such information, as revealed by the phosphate
      assay that we use here, should allow us to address hypotheses concerning the
      concentration of phosphate available to planktonic microorganisms in aquatic
      systems.

PMID- 10894538
TI  - The sedimentary structure of linear sand dunes
AB  - Linear sand dunes--dunes that extend parallel to each other rather than in star
      like or crescentic forms--are the most abundant type of desert sand dune. But
      because their development and their internal structure are poorly understood,
      they are rarely recognized in the rock record. Models of linear dune development
      have not been able to take into account the sub-surface structure of existing
      dunes, but have relied instead either on the extrapolation of short-term
      measurements of winds and sediment transport or on observations of near-surface
      internal sedimentary structures. From such studies, it has not been clear if
      linear dunes can migrate laterally. Here we present images produced by ground
      penetrating radar showing the three-dimensional sedimentary structure of a linear
      dune in the Namib sand sea, where some of the world's largest linear dunes are
      situated. These profiles show clear evidence for lateral migration in a linear
      dune. Moreover, the migration of a sinuous crest-line along the dune produces
      divergent sets of cross-stratification, which can become stacked as the dune
      height increases, and large linear dunes can support superimposed dunes that
      produce stacked sets of trough cross-stratification. These clear structural
      signatures of linear dunes should facilitate their recognition in geological
      records.

PMID- 10894539
TI  - The formation of plagioclase chains during convective transfer in basaltic magma
AB  - The basaltic rock in the lower part of the thick Holyoke lava flow in Connecticut
      and Massachusetts has been shown to have a remarkable texture, with crystals of
      feldspar linked together in a continuous three-dimensional network of chains.
      Heating experiments have revealed that this network persists to temperatures
      where the rock is 75% liquid, and therefore the network was interpreted to have
      formed at an early stage of crystallization and to have played an important role
      in the compaction of crystal mush in the lower part of the flow. Despite the
      texture's importance to our understanding of how such basalt flows form, the
      origin of the texture has remained uncertain. Here we show that, although the
      network is present in the lower third of the flow, it was actually formed in the
      upper solidification front and was transported down in plumes of dense crystal
      mush. Convection of this type has been postulated for intrusive magma chambers,
      but corroborative field evidence has been equivocal, especially in lava lakes and
      flows. Preservation of the roof-generated texture in the lower part of a thick
      flood-basalt flow therefore constitutes important evidence for the role of
      convection in the solidification and differentiation of a simple magma sheet.

PMID- 10894540
TI  - Valuation of consumption and sale of forest goods from a Central American rain
      forest
AB  - Researchers recognize that society needs accurate and comprehensive estimates of
      the economic value of rain forests to assess conservation and management options.
      Valuation of forests can help us to decide whether to implement policies that
      reconcile the value different groups attach to forests. Here we have measured the
      value of the rain forest to local populations by monitoring the foods,
      construction and craft materials, and medicines consumed or sold from the forest
      by 32 Indian households in two villages in Honduras over 2.5 years. We have
      directly measured the detailed, comprehensive consumption patterns of rain forest
      products by an indigenous population and the value of that consumption in local
      markets. The combined value of consumption and sale of forest goods ranged from
      US$17.79 to US$23.72 per hectare per year, at the lower end of previous estimates
      (between US$49 and US$1,089 (mean US$347) per hectare per year). Although
      outsiders value the rain forest for its high-use and non-use values, local people
      receive a small share of the total value. Unless rural people are paid for the
      non-local values of rain forests, they may be easily persuaded to deforest.

PMID- 10894541
TI  - Parallel evolution of virulence in pathogenic Escherichia coli.
AB  - The mechanisms underlying the evolution and emergence of new bacterial pathogens
      are not well understood. To elucidate the evolution of pathogenic Escherichia
      coli strains, here we sequenced seven housekeeping genes to build a phylogenetic
      tree and trace the history of the acquisition of virulence genes. Compatibility
      analysis indicates that more than 70% of the informative sites agree with a
      single phylogeny, suggesting that recombination has not completely obscured the
      remnants of ancestral chromosomes. On the basis of the rate of synonymous
      substitution for E. coli and Salmonella enterica (4.7 x 10(-9) per site per
      year), the radiation of clones began about 9 million years ago and the highly
      virulent pathogen responsible for epidemics of food poisoning, E. coli O157:H7,
      separated from a common ancestor of E. coli K-12 as long as 4.5 million years
      ago. Phylogenetic analysis reveals that old lineages of E. coli have acquired the
      same virulence factors in parallel, including a pathogenicity island involved in
      intestinal adhesion, a plasmid-borne haemolysin, and phage-encoded Shiga toxins.
      Such parallel evolution indicates that natural selection has favoured an ordered
      acquisition of genes and the progressive build-up of molecular mechanisms that
      increase virulence.

PMID- 10894542
TI  - Negative genetic correlation between male sexual attractiveness and survival.
AB  - Indirect selection of female mating preferences may result from a genetic
      association between male attractiveness and offspring fitness. The offspring of
      attractive males may have enhanced growth, fecundity, viability or
      attractiveness. However, the extent to which attractive males bear genes that
      reduce other fitness components has remained unexplored. Here I show that sexual
      attractiveness in male guppies (Poecilia reticulata) is heritable and genetically
      correlated with ornamentation. Like ornamentation, attractiveness may be
      substantially Y-linked. The benefit of mating with attractive males, and thus
      having attractive sons, is opposed by strong negative genetic correlation between
      attractiveness and both offspring survival and the number of sons maturing. Such
      correlations suggest either antagonistic pleiotropy between attractiveness and
      survival or linkage disequilibrium between attractive and deleterious alleles.
      The presence of many colour pattern genes on or near the non-recombining section
      of the Y chromosome may facilitate the accumulation of deleterious mutations by
      genetic hitchhiking. These findings show that genes enhancing sexual
      attractiveness may be associated with pleiotropic costs or heavy mutational
      loads.

PMID- 10894543
TI  - Identification of receptors for neuromedin U and its role in feeding.
AB  - Neuromedin U (NMU) is a neuropeptide with potent activity on smooth muscle which
      was isolated first from porcine spinal cord and later from other species. It is
      widely distributed in the gut and central nervous system. Peripheral activities
      of NMU include stimulation of smooth muscle, increase of blood pressure,
      alteration of ion transport in the gut, control of local blood flow and
      regulation of adrenocortical function. An NMU receptor has not been molecularly
      identified. Here we show that the previously described orphan G-protein-coupled
      receptor FM-3 (ref. 15) and a newly discovered one (FM-4) are cognate receptors
      for NMU. FM-3, designated NMU1R, is abundantly expressed in peripheral tissues
      whereas FM-4, designated NMU2R, is expressed in specific regions of the brain.
      NMU is expressed in the ventromedial hypothalamus in the rat brain, and its level
      is significantly reduced following fasting. Intracerebroventricular
      administration of NMU markedly suppresses food intake in rats. These findings
      provide a molecular basis for the biochemical activities of NMU and may indicate
      that NMU is involved in the central control of feeding.

PMID- 10894544
TI  - Initiation of neural induction by FGF signalling before gastrulation.
AB  - During neural induction, the 'organizer' of the vertebrate embryo instructs
      neighbouring ectodermal cells to become nervous system rather than epidermis.
      This process is generally thought to occur around the mid-gastrula stage of
      embryogenesis. Here we report the isolation of ERNI, an early response gene to
      signals from the organizer (Hensen's node). Using ERNI as a marker, we present
      evidence that neural induction begins before gastrulation--much earlier in
      development than previously thought. We show that the organizer and some of its
      precursor cells produce a fibroblast growth factor signal, which can initiate,
      and is required for, neural induction.

PMID- 10894545
TI  - Point mutation in an AMPA receptor gene rescues lethality in mice deficient in
      the RNA-editing enzyme ADAR2.
AB  - RNA editing by site-selective deamination of adenosine to inosine alters codons
      and splicing in nuclear transcripts, and therefore protein function. ADAR2 (refs
      7, 8) is a candidate mammalian editing enzyme that is widely expressed in brain
      and other tissues, but its RNA substrates are unknown. Here we have studied ADAR2
      mediated RNA editing by generating mice that are homozygous for a targeted
      functional null allele. Editing in ADAR2-/- mice was substantially reduced at
      most of 25 positions in diverse transcripts; the mutant mice became prone to
      seizures and died young. The impaired phenotype appeared to result entirely from
      a single underedited position, as it reverted to normal when both alleles for the
      underedited transcript were substituted with alleles encoding the edited version
      exonically. The critical position specifies an ion channel determinant, the Q/R
      site, in AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor
      GluR-B pre-messenger RNA. We conclude that this transcript is the physiologically
      most important substrate of ADAR2.

PMID- 10894546
TI  - Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus
      encoded human beta-globin.
AB  - The stable introduction of a functional beta-globin gene in haematopoietic stem
      cells could be a powerful approach to treat beta-thalassaemia and sickle-cell
      disease. Genetic approaches aiming to increase normal beta-globin expression in
      the progeny of autologous haematopoietic stem cells might circumvent the
      limitations and risks of allogeneic cell transplants. However, low-level
      expression, position effects and transcriptional silencing hampered the
      effectiveness of viral transduction of the human beta-globin gene when it was
      linked to minimal regulatory sequences. Here we show that the use of recombinant
      lentiviruses enables efficient transfer and faithful integration of the human
      beta-globin gene together with large segments of its locus control region. In
      long-term recipients of unselected transduced bone marrow cells, tetramers of two
      murine alpha-globin and two human betaA-globin molecules account for up to 13% of
      total haemoglobin in mature red cells of normal mice. In beta-thalassaemic
      heterozygous mice higher percentages are obtained (17% to 24%), which are
      sufficient to ameliorate anaemia and red cell morphology. Such levels should be
      of therapeutic benefit in patients with severe defects in haemoglobin production.

PMID- 10894547
TI  - Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB
      activation.
AB  - Glycogen synthase kinase-3 (GSK-3)-alpha and -beta are closely related protein
      serine kinases, which act as inhibitory components of Wnt signalling during
      embryonic development and cell proliferation in adult tissues. Insight into the
      physiological function of GSK-3 has emerged from genetic analysis in Drosophila,
      Dictyostelium and yeast. Here we show that disruption of the murine GSK-3beta
      gene results in embryonic lethality caused by severe liver degeneration during
      mid-gestation, a phenotype consistent with excessive tumour necrosis factor (TNF)
      toxicity, as observed in mice lacking genes involved in the activation of the
      transcription factor activation NF-kappaB. GSK-3beta-deficient embryos were
      rescued by inhibition of TNF using an anti-TNF-alpha antibody. Fibroblasts from
      GSK-3beta-deficient embryos were hypersensitive to TNF-alpha and showed reduced
      NF-kappaB function. Lithium treatment (which inhibits GSK-3; refs 8, 9)
      sensitized wild-type fibroblasts to TNF and inhibited transactivation of NF
      kappaB. The early steps leading to NF-kappaB activation (degradation of I-kappaB
      and translocation of NF-kappaB to the nucleus) were unaffected by the loss of GSK
      3beta, indicating that NF-kappaB is regulated by GSK-3beta at the level of the
      transcriptional complex. Thus, GSK-3beta facilitates NF-kappaB function.

PMID- 10894548
TI  - Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth.
AB  - There are about 800 genes in Saccharomyces cerevisiae whose transcription is cell
      cycle regulated. Some of these form clusters of co-regulated genes. The 'CLB2'
      cluster contains 33 genes whose transcription peaks early in mitosis, including
      CLB1, CLB2, SWI5, ACE2, CDC5, CDC20 and other genes important for mitosis. Here
      we find that the genes in this cluster lose their cell cycle regulation in a
      mutant that lacks two forkhead transcription factors, Fkh1 and Fkh2. Fkh2 protein
      is associated with the promoters of CLB2, SWI5 and other genes of the cluster.
      These results indicate that Fkh proteins are transcription factors for the CLB2
      cluster. The fkh1 fkh2 mutant also displays aberrant regulation of the 'SIC1'
      cluster, whose member genes are expressed in the M-G1 interval and are involved
      in mitotic exit. This aberrant regulation may be due to aberrant expression of
      the transcription factors Swi5 and Ace2, which are members of the CLB2 cluster
      and controllers of the SIC1 cluster. Thus, a cascade of transcription factors
      operates late in the cell cycle. Finally, the fkh1 fkh2 mutant displays a
      constitutive pseudohyphal morphology, indicating that Fkh1 and Fkh2 may help
      control the switch to this mode of growth.

PMID- 10894549
TI  - Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M
      specific promoters.
AB  - Many cell-cycle-specific events are supported by stage-specific gene expression.
      In budding yeast, at least three different nuclear factors seem to cooperate in
      the periodic activation of G2/M-specific genes. Here we show, by using chromatin
      immunoprecipitation polymerase chain reaction assays, that a positive regulator,
      Ndd1, becomes associated with G2/M promoter regions in manner that depends on the
      stage in cell cycle. Its recruitment depends on a permanent protein-DNA complex
      consisting of the MADS box protein, Mcm1, and a recently identified partner Fkh2,
      a forkhead/winged helix related transcription factor. The lethality of Ndd1
      depletion is suppressed by fkh2 null mutations, which indicates that Fkh2 may
      also have a negative regulatory role in the transcription of G2/M-induced RNAs.
      We conclude that Ndd1-Fkh2 interactions may be the transcriptionally important
      process targeted by Cdk activity.

PMID- 10894550
TI  - Elevated UV-B radiation reduces genome stability in plants.
AB  - Long-term depletion of the stratospheric ozone layer contributes to an increase
      in terrestrial solar ultraviolet-B radiation. This has deleterious effects on
      living organisms, such as DNA damage. When exposed to elevated ultraviolet-B
      radiation (UV-B; 280-315 nm), plants display a wide variety of physiological and
      morphological responses characterized as acclimation and adaptation. Here we
      show, using special sun simulators, that elevated solar UV-B doses increase the
      frequency of somatic homologous DNA rearrangements in Arabidopsis and tobacco
      plants. Increases in recombination are accompanied by a strong induction of
      photolyase and Rad51 gene expression. These genes are putatively involved in
      major DNA repair pathways, photoreactivation and recombination repair. In mutant
      Arabidopsis plants that are deficient in photoreactivating ultraviolet-induced
      cyclobutane pyrimidine dimers, recombination under elevated UV-B regimes greatly
      exceeds wild-type levels. Our results show that homologous recombination repair
      pathways might be involved in eliminating UV-B-induced DNA lesions in plants.
      Thus, increases in terrestrial solar UV-B radiation as forecasted for the early
      21st century may affect genome stability in plants.

PMID- 10894551
TI  - Structure of the dimerized hormone-binding domain of a guanylyl-cyclase-coupled
      receptor.
AB  - The atrial natriuretic peptide (ANP) hormone is secreted by the heart in response
      to an increase in blood pressure. ANP exhibits several potent anti-hypertensive
      actions in the kidney, adrenal gland and vascular system. These actions are
      induced by hormone binding extracellularly to the ANP receptor, thereby
      activating its intracellular guanylyl cyclase domain for the production of cyclic
      GMP. Here we present the crystal structure of the glycosylated dimerized hormone
      binding domain of the ANP receptor at 2.0-A resolution. The monomer comprises two
      interconnected subdomains, each encompassing a central beta-sheet flanked by
      alpha-helices, and exhibits the type I periplasmic binding protein fold.
      Dimerization is mediated by the juxtaposition of four parallel helices, arranged
      two by two, which brings the two protruding carboxy termini into close relative
      proximity. From affinity labelling and mutagenesis studies, the ANP-binding site
      maps to the side of the dimer crevice and extends to near the dimer interface. A
      conserved chloride-binding site is located in the membrane distal domain, and we
      found that hormone binding is chloride dependent. These studies suggest
      mechanisms for hormone activation and the allostery of the ANP receptor.

PMID- 10894552
TI  - Laying a firm foundation for interdisciplinary research endeavours.

PMID- 10894553
TI  - Effect of thromboxane synthase inhibitor, CS-518, on propranolol-induced
      bronchoconstriction in guinea pigs.
AB  - Beta-adrenoreceptor antagonists, such as propranolol, can provoke severe
      bronchoconstriction in asthmatic subjects. Recently we developed an animal model
      of propranolol-induced bronchoconstriction and investigated the involvement of
      chemical mediators in this reaction. The purpose of this study was to elucidate
      the role of thromboxane A2 in the development of propranolol-induced
      bronchoconstriction after allergic bronchoconstriction. Passively sensitized
      guinea pigs were anesthetized and treated with diphenhydramine hydrochloride and
      were then artificially ventilated. Propranolol at a concentration of 10 mg/ml was
      inhaled 20 min after an aerosolized antigen challenge. A potent and selective
      thromboxane A2 synthase inhibitor, CS-518, in doses of 0.01, 0.1 and 1 mg/kg and
      vehicle were administered intravenously 15 min after the antigen challenge.
      Another study was performed in naive guinea pigs; ascending doses of methacholine
      (12.5, 25, 50, 100 and 200 microg/ml) were inhaled for 20 sec at 5-min intervals,
      10 min after intravenous administration of CS-518. Propranolol inhaled 20 min
      after the antigen challenge caused bronchoconstriction in sensitized guinea pigs.
      CS-518 administered 15 min after the antigen challenge significantly inhibited
      propranolol-induced bronchoconstriction in a dose-dependent manner, while CS-518
      did not influence the dose-dependent response to inhaled methacholine in naive
      guinea pigs. We conclude that thromboxane A2 contributes to the development of
      propranolol-induced bronchoconstriction following allergic reaction in our guinea
      pig model.

PMID- 10894554
TI  - Cytoprotective effect of rabeprazole against ethanol-induced gastric mucosal
      damage: possible involvement of nitric oxide.
AB  - The cytoprotective effect of rabeprazole, a new proton pump inhibitor, against
      ethanol-induced gastric mucosal damage was investigated in rats. Rats received
      intraperitoneal injections of rabeprazole once only or once daily for 3 days.
      Subsequently, the rats were given 1 ml of absolute ethanol by oral intubation.
      Some rats given rabeprazole were treated with N-omega-nitro-L-arginine methyl
      ester (L-NAME) or indomethacin. Repeated administration of rabeprazole
      significantly inhibited ethanol-induced gastric mucosal damage, although single
      administration of this drug did not. Pretreatment with L-NAME abolished the
      cytoprotective effect of rabeprazole. This inhibitory effect of L-NAME was
      reversed by L-arginine but not by D-arginine. Pretreatment with indomethacin did
      not influence the cytoprotective effect of rabeprazole. These results suggest
      that repeated intraperitoneal administration of rabeprazole has a cytoprotective
      effect against ethanol-induced gastric mucosal damage and that this effect may be
      mediated via nitric oxide but not via prostaglandins.

PMID- 10894555
TI  - Assessment of resveratrol bioavailability in the perfused small intestine of the
      rat.
AB  - Resveratrol, which is present in grapes, wine and peanuts, is believed to possess
      chemoprotective properties such as anticarcinogenic effects and to provide
      protection against cardiovascular diseases. Little is known, however, about its
      intestinal absorption. We investigated the absorption and metabolism of
      resveratrol by using an isolated preparation of luminally and vascularly perfused
      rat small intestine. A synthetic perfusate free from blood components was used as
      vascular medium with a perfluorocarbon as oxygen carrier. Luminal media consisted
      of a bicarbonate buffered sodium chloride solution spiked with resveratrol in
      physiological, nutritionally relevant concentrations (28, 34 and 57 micromol/l,
      respectively). Viability was maintained during the entire perfusion and no
      significant differences between resveratrol and control perfusions for oxygen
      consumption, arterial pressure, lactate-pyruvate ratio and acid-base homeostasis
      were observed. Vascular uptake of luminally administered resveratrol was 20.5%.
      The majority of the absorbed resveratrol was conjugated to yield resveratrol
      glucuronide (16.8%), which was also the main luminal metabolite (11.2%). Lesser
      amounts of resveratrol sulfate, 3.0% and 0.3%, were found on the luminal and
      vascular side, respectively, while only minute amounts of resveratrol and
      resveratrol conjugates (1.9%) were found in the intestinal tissue. The structures
      of the resveratrol conjugates were verified by liquid chromatography coupled with
      mass spectometry (LC-MS). The results demonstrate an ample uptake and metabolic
      conversion of resveratrol. The proposed perfusion model serves as a tool to
      evaluate intestinal absorption and metabolic handling of phytochemicals, a
      pertinent input to the ongoing discussion about their health benefits.

PMID- 10894556
TI  - Neutral sphingomyelinase-inhibiting guanidines prevent herpes simplex virus-1
      replication.
AB  - We synthesized a series of new guanidinium derivatives and studied the inhibitory
      activity on both neutral sphingomyelinase and herpes simplex virus-1 (HSV-1)
      replication. The lipophilic quality of the molecules was found to be correlated
      with the inhibitory potential of the compounds. Undecylidene-aminoguanidine was
      superior to derivatives with 10, 8 or 6 carbon atoms whereas propylidene
      aminoguanidine was completely inactive. Decylidene-aminoguanidine was the most
      active derivative, with 10 carbon atoms. Various cyclic saturated isomers were
      inferior to the linear molecule. Aromatic cyclic residues were superior to
      saturated cyclic residues. The most active compound was a derivative containing
      11 carbon atoms, undecylidene-aminoguanidine (C11AG), which inhibited the
      replication of HSV-1 by 50% at a concentration of 2.6 microM while cytotoxic
      adverse effects were only observed at a concentration of 31 microM. Expression of
      immediate early gene ICP-4 and concomitantly of HSV-1 specific DNA replication
      was found to be a target of C11AG. This result suggests that C11AG interferes
      with cellular signal transduction mechanisms that regulate expression of HSV-1
      immediate early genes. C11AG was shown to inhibit neutral sphingomyelinase
      without affecting phospholipase A2, phosphatidylcholine-specific phospholipase C
      and phospholipase D.

PMID- 10894557
TI  - Polymerase chain reaction in Lyme borreliosis.
AB  - Many bacterial and/or viral infections can affect several organs and apparatuses.
      Some of these infectious agents may be implicated in the pathogenesis and
      evolution of chronic connective and articular diseases. Such agents may trigger
      the start of articular chronic diseases or may play a role in maintaining the
      symptoms. In this study, we evaluated the sensitivity and specificity of
      polymerase chain reaction (PCR) in Lyme borreliosis, in patients with a confirmed
      diagnosis of the disease after clinical examination and standard serologic tests.
      There were 18 true positive results from nine samples from patients with present
      clinical signs, positive PCR, negative Western blot and/or enzyme-linked
      immunosorbent assay (ELISA) and nine samples with present clinical signs and
      positive ELISA and/or Western blot. The 51 true negative results were negative in
      all three methods used. There were 24 false positive results, positive for
      clinical signs, ELISA and/or Western blot but negative for PCR.

PMID- 10894558
TI  - Radiolabelled peptides--promises and pitfalls.

PMID- 10894559
TI  - A study of doses to the hands during dispensing of radiopharmaceuticals.
AB  - Radiation doses to both the fingertip and finger base of staff preparing
      radiopharmaceuticals in a radionuclide dispensary have been monitored for more
      than 5 years. The records show a fall in dose thought to be due, largely, to the
      introduction of all-glass (lead) syringe shields. In 1998, the annual radiation
      dose (mean +/- standard deviation) to the fingertip had fallen to 83+/-11 mSv,
      which corresponded to 0.18 mSv per 10 GBq 99Tc(m) handled. There was less
      reduction in dose to the finger base, which, in 1998, was 70% of that to the
      fingertip. To study the effect of a syringe shield on the distribution of dose
      across the hands, model hands were constructed and a gamma extremity monitoring
      system (GEMS) was used to measure dose. When a radiopharmaceutical is dispensed,
      contributions to the dose from activity in the vial and syringe change during the
      procedure. As a result, relative doses to different fingers and the ratios of
      doses to the tip and base of each finger will fluctuate throughout dispensing. In
      the absence of a syringe shield, the front tip of the index finger received the
      greatest radiation dose. When a syringe shield was used, doses were lower and the
      dose distribution was completely different. These findings have important
      implications in terms of compliance with the new UK Ionizing Radiations
      Regulations, where the dose limit is applied to 'the dose averaged over any area
      of 1 cm2 regardless of the area exposed'.

PMID- 10894560
TI  - Recombinant human thyrotropin (rhTSH) in the management of differentiated thyroid
      cancer.
AB  - Recombinant human thyrotropin (rhTSH) has been evaluated in 38 patients with
      differentiated thyroid cancer. The patients had all been treated previously by
      operation and 31 had received radioiodine 131I. The patients continued to take
      thyroid hormone and changed to a low iodine diet for 14 days before and
      throughout the week of testing. The rhTSH was injected intramuscularly on two
      consecutive days, 74 MBq 131I was administered on the next day and scintigraphy
      completed 48 h after that. TSH was measured before administration of 131I, and
      thyroglobulin after the scan. All patients preferred this method to withdrawal of
      thyroid hormone, but 45% had mild symptoms including headache and nausea. The
      average TSH was 127 mU x l(-1), and was inversely related to the weight of the
      patients. Thirty-four had negative scans with a mean uptake of 0.06%.
      Thyroglobulin values above 10 ng x ml(-1) were found in seven patients, of whom
      four had similar findings when scanned after withdrawal of thyroid hormone. Of
      four with positive scans, two had undetectable thyroglobulin. The rate of
      clearance of 131I was compared in patients studied at 72 h who were hypothyroid
      and at 48 h in euthyroid patients given rhTSH and was found to be longer in the
      latter. We conclude that rhTSH can be used to stimulate thyroid tissue to trap
      131I and secrete thyroglobulin. Both scan and thyroglobulin should be obtained.
      The method is well tolerated.

PMID- 10894561
TI  - Fixed dosage of 131I for remnant ablation in patients with differentiated thyroid
      carcinoma without pre-ablative diagnostic 131I scintigraphy.
AB  - Differentiated thyroid cancer is treated by (near) total thyroidectomy followed
      by radioiodine (131I) ablation of the residual active tissue in the thyroid bed.
      Controversy remains concerning the use and the dose of pre-ablative diagnostic
      131I scintigraphy. This study was designed to assess the efficacy of thyroid
      ablation by high-dose 131I without pre-ablative diagnostic 131I scintigraphy.
      Ninety-three patients were treated with (near) total thyroidectomy and with a
      high ablative dose of 131I (3700-7400 MBq). A preablative 131I diagnostic
      scintigram was not performed. To assess the efficacy of the treatment, all
      patients were studied with a diagnostic 131I scintigram and with thyroglobulin
      plasma assays 1 year later after withdrawal of L-thyroxine for 4-6 weeks. The
      main criterion for a successful ablation was the absence of thyroid bed activity.
      An additional criterion was a thyroglobulin value of <10 microg x l(-1).
      Successful ablation according to the main criterion was obtained in 88% of
      patients. Forty patients (43%) showed no neck uptake and had undetectable serum
      thyroglobulin. Twenty-two patients (25%) had serum thyroglobulin concentrations
      between 1 and 10 microg x l(-1). Twenty-six patients (27%) had thyroglobulin >10
      microg x l(-1), 19 patients showing residual thyroid uptake or metastatic
      lesions. We conclude that high-dose radioiodine ablation without prior diagnostic
      scintigraphy results in a high rate of successful ablation, preventing repeat
      131I treatment.

PMID- 10894562
TI  - Assessment of hepatic blood flow by PET with 15O water: correlation between per
      rectal portal scintigraphy with 99Tc(m)-pertechnetate and scintigraphy with
      99Tc(m)-GSA.
AB  - We performed positron emission tomography with 15O water (H2(15)O) to measure
      hepatic arterial and portal blood flow. In addition, portal haemodynamics and
      hepatic functional reserve were measured by per-rectal portal scintigraphy and
      scintigraphy with galactosyl human serum albumin, respectively. We studied 15
      patients who had cirrhosis of the liver with underlying viral infection. After
      the intravenous injection of H2(15)O, positron emission tomography was performed.
      Blood samples were obtained after beginning the emission scan. The blood samples
      and positron emission tomographic images were analysed to calculate the
      radioactivity in the blood and liver. One-compartment model analysis was used to
      estimate hepatic arterial and portal blood flow. Computer acquisition of gamma
      camera data was started just before the injection of 99Tc(m)-galactosyl human
      serum albumin. A receptor index and an index of blood clearance were calculated
      on the basis of the radioactivity of the liver and heart. A 99Tc(m)-pertechnetate
      solution was instilled into the rectum; serial scintigrams were performed and
      radioactivity curves for the liver and heart were recorded sequentially. A per
      rectal portal shunt index was calculated from the curves. Median portal blood
      flow was 80 ml x 100 g(-1) x min(-1), median hepatic arterial blood flow was 56
      ml x 100 g(-1) x min(-1), and median total hepatic blood flow was 138 ml x 100 g(
      1) x min(-1) in patients with cirrhosis. The correlations between portal blood
      flow and the Child-Turcotte classification score, portal shunt index and receptor
      index were all significant. Our results show that hepatic arterial and portal
      blood flow can be measured by positron emission tomography with H2(15)O non
      invasively and physiologically. This technique may be useful in
      pathophysiological studies of liver disease.

PMID- 10894563
TI  - Measurement of plasma volume using 99Tc(m)-labelled DMP-HSA.
AB  - Red cell volume (RCV) and plasma volume (PV) measurements are performed routinely
      in nuclear medicine departments to diagnose a number of haematological disorders.
      Currently, 125I-HSA is used as a plasma tracer and 99Tcm-labelled red cells to
      determine red cell volume. 125I-HSA is not always readily available, leading to
      inconvenience for patients and medical practitioners. Due to the availability of
      99Tcm in nuclear medicine departments, the use of albumin labelled with 99Tcm was
      investigated. A new 99Tcm-human serum albumin labelling kit (99Tcm-DMP-HSA) was
      developed by Verbeke and supplied for use in this study. The main aim of the
      study was to investigate the use of 99Tcm-DMP-HSA for PV determination. Secondly,
      the feasibility to determine red cell and plasma volume simultaneously using
      99Tcm as radionuclide in both instances was investigated. Fourteen healthy
      volunteers were enrolled in the dual-phase study. During the first study, 99Tcm
      DMP-HSA was used as tracer to calculate PV (PV1a) after intravenous
      administration. Subsequently, 99Tcm-labelled red cells were administered and the
      PV (PV1b) and RCV (RCV1) were calculated. The second study was repeated within 2
      weeks using the conventional method. 125I-HSA and 99Tcm-labelled red cells were
      administered simultaneously. The PV (PV2) and RCV (RCV2) were calculated. We
      found that the redistribution of 99Tcm-DMP-HSA is faster than that of 125I-HSA;
      therefore, the plasma counts obtained at different times were back-extrapolated
      to time zero for plasma volume calculations. The mean values for the different
      calculated PVs were 2964+/-470 ml for PV1a, 3006+/-623 ml for PV1b and 3001+/-530
      ml for PV2, the reference PV. The confidence intervals indicate no significant
      differences between plasma volumes PV1a and PV2 and plasma volumes PV1a and PV1b.
      The mean calculated RCV1 was 2130+/-322 ml; that of RCV2 was 2128+/-353 ml. The
      difference between RCV1 and RCV2 was not significant. Our results indicate that
      99Tcm-DMP-HSA could be used for plasma volume calculation. Red cell and plasma
      volumes can be calculated simultaneously using 99Tcm as radionuclide in both
      cases.

PMID- 10894564
TI  - Voxel significance mapping using local image variances in subtraction ictal SPET.
AB  - Subtraction ictal SPET co-registered to MRI (SISCOM) has been shown to aid
      epileptogenic localization and improve surgical outcome in partial epilepsy
      patients. This paper reports a method of identifying significant areas of
      epileptogenic activation in the SISCOM subtraction image, taking into account
      normal variation between sequential 99Tcm-ethyl cysteinate diethylester SPET
      scans of single individuals, and attempts to assess the clinical value of
      statistical mapping in subtraction SPET. Non-linear inter-subject registration is
      used to combine a group of subtraction images into a common anatomical framework.
      A map of the pixel intensity standard deviation values in the subtraction images
      is created, and this map is non-linearly registered to a patient's SISCOM
      subtraction image. Pixels in the patient subtraction image were then evaluated
      based upon the statistical characteristics of corresponding pixels in the atlas.
      SISCOM images created with the voxel variance method were rated higher in quality
      than the conventional image variance method in 15 patients. No difference in
      localization rate was observed between the voxel variance mapping and image
      variance methods. The voxel significance mapping method was shown to improve the
      quality of clinical SISCOM images.

PMID- 10894565
TI  - Accuracy in gamma camera measurements of point source velocities.
AB  - Mucociliary clearance is impaired in many diseases of the respiratory system. We
      have developed a method for measuring tracheal mucus velocity by the dynamic
      study of a single point source of radioactivity deposited in the trachea by
      cricothyroid injection. Preliminary results suggest that patients with airways
      disease have very low tracheal mucus velocities (<2 mm x min(-1)). The aim of
      this experiment was to explore the ability of current scintillation detection
      systems to track a single point as it moves in a dynamic study in small
      increments and at low velocity (movements of the order of 1 mm). Background noise
      was estimated to contribute an error in positioning of 0.16 mm (1 standard
      deviation). Overall errors in velocity were estimated at 0.2 mm x min(-1). This
      suggests that standard instrumentation in use in most nuclear medicine
      departments has the capacity to measure accurately velocities as low as 1 mm x
      min(-1).

PMID- 10894566
TI  - Assessment of the effect of vincristine on the biodistribution of 99Tcm-labelled
      glucoheptonic acid in female Balb/c mice.
AB  - There is evidence that the biodistribution and the pharmacokinetics of 99Tcm
      radiopharmaceuticals can be modified by some drugs, pathological states,
      irradiation and surgical procedures. Vincristine have been widely used in various
      chemotherapeutic protocols in oncology. We are trying to develop an animal model
      to assess the toxicology in different organs of compounds used as therapeutic
      drugs. We have studied the effect of vincristine on the distribution of 99Tcm
      glucoheptonic acid (99Tcm-GHA) in female mice. After the last dose of
      vincristine, 99Tcm-GHA (7.4 MBq) was injected, the animals sacrificed and the
      percentage of radioactivity determined in the isolated organs. The percentage of
      activity was significantly decreased in the uterus, ovary, spleen, thymus, lymph
      nodes (inguinal and mesenteric), kidney and heart, but was not significantly
      altered in the lung, liver, pancreas, stomach, thyroid, brain and bone. Our
      results can be explained by the metabolic, toxic, therapeutic and
      immunosuppressive actions of this chemotherapeutic drug.

PMID- 10894567
TI  - Measles virus as a risk for inflammatory bowel disease: an unusually tolerant
      approach.

PMID- 10894568
TI  - Outcomes and costs of care in hepatitis C: combination therapy scores again.

PMID- 10894569
TI  - Colorectal cancer screening by primary care physicians: what are the next steps?

PMID- 10894570
TI  - Iodinated contrast sensitivity in ERCP.
AB  - Iodine contrast media are detectable in the bloodstream after ERCP, and
      sensitivity reactions have been described. The risk is very small, and the
      phenomenon is therefore difficult to study. This review discusses the possible
      need for preventative strategies, and recommends that endoscopists consider the
      issue and define their own policies.

PMID- 10894571
TI  - Primary gallbladder cancer: recognition of risk factors and the role of
      prophylactic cholecystectomy.
AB  - The objective of this article is to review the available literature on the
      epidemiology, predisposing factors, and conditions associated with primary
      gallbladder cancer, and to discuss the role of prophylactic cholecystectomy in
      high-risk patient populations. Gallbladder cancer is a highly malignant tumor
      with a poor 5-yr-survival rate. It is a tumor of the elderly and has striking
      genetic, racial, and geographic characteristics, with an extremely high
      prevalence in Native Americans and Chileans. Cholelithiasis is a well-established
      risk factor for gallbladder cancer and the risk seems to correlate with stone
      size. Polyps that are >1 cm, single, sessile, and echopenic are associated with a
      higher risk of malignancy. Anomalous junction of pancreaticobiliary ducts
      (AJPBD), especially without choledochal cyst, and porcelain gallbladder are
      additional factors that predispose to gallbladder cancer. Lesser associations
      include chronic bacterial infections of the gallbladder, typhoid carrier state,
      certain occupational and environmental carcinogens, hormonal changes in women,
      and certain social, dietary, and familial factors. It is important to identify
      high-risk groups for gallbladder cancer because of the dismal nature of this
      tumor. In patients with porcelain gallbladder and anomalous junction of the
      pancreatic and biliary ducts, cholecystectomy is recommended provided that the
      patient is a good operative candidate. Patients with large solitary polyps or
      gallstones require close ultrasonic follow-up. With the advent of endoscopic
      ultrasound it is expected that early changes of malignancy in polyps will be
      reliably detected, and more patients will potentially be cured with a simple
      cholecystectomy. Through a MEDLINE/PAPERCHASE search we identified and reviewed
      articles regarding gallbladder cancer published in English-language journals
      between 1966 and 1999, using the key words biliary tract and gallbladder
      diseases, cancer, neoplasms, surgery, cholelithiasis, gallstones, cholecystitis,
      gallbladder polyps, risk factors, chemical industry, occupational diseases,
      typhoid, porcelain gallbladder, bacteremia, and precancerous conditions. We also
      used the bibliography of relevant articles to increase our search. A total of 122
      publications were selected using the mentioned data source.

PMID- 10894572
TI  - Dysphagia lusoria: clinical aspects, manometric findings, diagnosis, and therapy.
AB  - OBJECTIVE: The lusorian artery is a rare anomaly of the right subclavian artery.
      This artery arises from the aortic arch distal of the left subclavian artery,
      crossing the midline behind the esophagus. Normally this anomaly causes no
      symptoms. Sometimes dysphagia first appears above the age of 40 yr. METHODS: In
      the period of 1992-1997, the diagnosis of an aberrant right subclavian artery was
      made in five patients with dysphagia who were referred to a small community
      hospital. A sixth patient had a right-sided aorta with an aberrant left
      subclavian artery. RESULTS: Endoscopy revealed a pulsating impression in the
      esophagus of three patients. Four patients had coexisting esophageal
      abnormalities. Barium contrast examination of the esophagus showed a
      characteristic diagonal impression at the level of the fourth thoracic vertebra
      in all patients. Computed tomography and angiography confirmed the diagnosis and
      excluded aneurysms. Manometric investigation of the esophagus revealed
      nonspecific abnormalities in five patients. Drug treatment was sufficient in
      three patients (mean follow-up, 6.2 yr). Three patients were operated upon
      because of persistent dysphagia. Through a cervical approach the artery was
      ligated near its root and connected with the right carotid artery.
      Postoperatively two patients became symptom-free, the other patient still has
      intermittent dysphagia. CONCLUSION: Dysphagia can be caused by a rare anomaly of
      the subclavian artery. The diagnosis can be overlooked at endoscopy, but barium
      contrast study of the esophagus will reveal the abnormality. In patients with
      coexisting esophageal abnormalities the finding may be incidental and specific
      conservative treatment may be sufficient. Manometry cannot be used to diagnose
      this condition or to predict surgical outcome. When the symptoms are intractable,
      surgical correction should be considered even if coexisting esophageal
      abnormalities are present.

PMID- 10894573
TI  - Manometry of the upper esophageal sphincter and pharynx is not useful in
      unselected patients referred for esophageal testing.
AB  - OBJECTIVE: We sought to determine whether routinely performing upper esophageal
      sphincter/pharyngeal (UES/P) manometry in patients referred for esophageal
      testing alters clinical practice. METHODS: Clinical history along with
      radiography and manometry studies were reviewed in 470 patients referred for
      manometry. A total of 435 (92.6%) were found to have adequate evaluation of the
      UES/P and were included in the study. RESULTS: Of 435 studies, 80 (17.7%) had one
      or more UES/P abnormalities. Indications for these 80 studies were dysphagia in
      30 cases (37.5%), chest pain in 26 (32.5%), both in four (5.0%), and other in 20
      (25%). There were 85 manometric abnormalities in the 80 studies: hypertensive UES
      in 16 cases (18.8%), incomplete UES relaxation in 38 (44.7%), hypertensive
      pharynx in seven (8.2%), hypotensive pharynx in 15 (17.6%), and abnormal
      coordination in nine (10.6%). A total of 41 patients had a barium study, which
      was normal in 11 cases (26%), confirmed the problem in 16 (40%), and suggested
      another problem in 14 (34%). In 17 patients (21%), there was clinical suspicion
      for an oropharyngeal disorder before manometry, whereas in 58 cases it was an
      unexpected finding. Of the 58 patients with an unexpected finding, therapy based
      on this finding was offered in six (three esophageal dilations, two dietary
      changes, and one swallowing therapy). If patients with concomitant esophageal
      body disorders are excluded, in only three patients an unexpected UES finding led
      to change in management. CONCLUSIONS: An unexpected UES/P finding resulted in a
      change in therapy in only six of the manometries. Barium esophagogram was
      diagnostic of the oropharyngeal abnormality in nearly two-thirds of the patients
      in whom it was clinically suspected. These data, along with limited therapeutic
      options, suggest limited usefulness for routine UES/P manometry.

PMID- 10894574
TI  - The spectrum of pediatric eosinophilic esophagitis beyond infancy: a clinical
      series of 30 children.
AB  - OBJECTIVES: Eosinophilic esophagitis, previously confused with esophageal
      inflammation due to gastroesophageal reflux, has recently begun to be
      distinguished from it. We undertook this analysis of our large series of children
      with the condition to clarify its spectrum: its presenting symptoms; its relation
      to allergy, respiratory disease, and reflux; its endoscopic and histological
      findings; and its diagnosis and therapy. METHODS: We analyzed the details of our
      clinical series of 30 children with eosinophilic esophagitis, defining it as > or
      =5 eosinophils per high power field in the distal esophageal epithelium.
      Retrospective chart review was supplemented by prospective, blinded, duplicate
      quantitative evaluation of histology specimens, and by telephone contact with
      some families to clarify subsequent course. Presentation and analysis of the
      series as a whole is preceded by a case illustrating a typical presentation with
      dysphagia and recurrent esophageal food impactions. RESULTS: Presenting symptoms
      encompass vomiting, pain, and dysphagia (some with impactions or strictures).
      Allergy, particularly food allergy, is an associated finding in most patients,
      and many have concomitant asthma or other chronic respiratory disease. A subtle
      granularity with furrows or rings is newly identified as the endoscopic herald of
      histological eosinophilic esophagitis. Histological characteristics include
      peripapillary or juxtaluminal eosinophil clustering in certain cases. Association
      with eosinophilic gastroenteritis occurs, but is not common. Differentiation from
      gastroesophageal reflux disease is approached by analyzing eosinophil density and
      response to therapeutic trials. Therapy encompasses dietary elimination and anti
      inflammatory pharmacotherapy. CONCLUSION: Awareness of the spectrum of
      eosinophilic esophagitis should promote optimal diagnosis and treatment of this
      elusive entity, both in children and in adults.

PMID- 10894575
TI  - Topographic patterns of intestinal metaplasia and gastric cancer.
AB  - OBJECTIVE: The role of intestinal metaplasia in gastric oncogenesis has been
      demonstrated by both cross-sectional and longitudinal studies. This study was
      designed to determine whether, in a population at high risk for gastric cancer,
      different topographical patterns and phenotypes of intestinal metaplasia were
      associated with different degrees of cancer risk. METHODS: A total of 68
      Colombian patients with gastric cancer and 67 controls with nonulcer dyspepsia
      were studied by an extensive biopsy protocol. Intestinal metaplasia was assessed
      semiquantitatively by histology and was characterized histochemically. In both
      patients and controls, the Spearman's correlation test was applied to the test if
      the gastric distribution of metaplastic lesions resulted in specific
      topographical patterns associated with different risks for cancer. RESULTS: Four
      topographical patterns of intestinalization emerged: 1) "Focal," in 14 cancer
      patients and 16 controls; 2) "Antrum-predominant," in seven cancer patients and
      six controls; 3) "Magenstrasse" (involving the lesser curvature from cardia to
      pylorus) in 25 cancer patients and four controls. This pattern was associated
      with higher cancer risk (OR = 5.7; 95% CI: 1.3-26) than were the two less
      extensive patterns; and 4) "Diffuse," involving essentially the entire gastric
      mucosa with the exception of the fundus, was unique to 13 cancer patients. The OR
      for cancer was 12.2; 95% CI: 2.0-72.9. Incomplete-type metaplasia significantly
      correlated with the extent of total metaplasia and was also associated with
      greater cancer risk. CONCLUSIONS: In a population with high risk for gastric
      cancer, the extension of intestinal metaplasia correlates with the extent of its
      "incomplete" phenotype and is significantly associated with increased cancer
      risk. Both the extent and location of intestinal metaplasia along the lesser
      curvature (from the cardia to the prepyloric zones) identify patients with the
      highest cancer risk.

PMID- 10894576
TI  - Gastrointestinal symptoms and subjects cluster into distinct upper and lower
      groupings in the community: a four nations study.
AB  - OBJECTIVE: It is unknown whether distinct functional GI (GI) symptom groupings
      occur in the general population and whether these are similar across different
      cultures. Although symptom-based diagnostic criteria have been developed for
      upper and lower GI syndromes (the Rome criteria), the classification is
      controversial. We aimed to identify whether independent symptom-based subgroups
      exist in four countries consistent with the Rome criteria. METHODS: Random
      samples of the community were mailed a validated questionnaire based on the Bowel
      Disease Questionnaire in Rochester, MN (n = 2,220), in Sydney, Australia (n =
      1,135), and in Essen, Germany (n = 500). A different validated questionnaire was
      mailed to a random sample in Osthammar, Sweden (n = 1,517). Only the common
      questions (n = 22) were used in the current analysis, and these were essentially
      identical in wording. The underlying structure of the item responses was examined
      using factor analysis. Initial factors were extracted using principal components
      analysis and then rotated using Varimax. Clustering of symptoms among individuals
      was examined though cluster analysis, using the factors as the basis for
      clustering. RESULTS: Response rates varied from 64% to 80%; responders and
      nonresponders were similar sociodemographically. All four studies yielded similar
      factor structures. All countries reported symptom groupings consistent with the
      irritable bowel syndrome (IBS), dyspepsia and/or gastroesophageal reflux, and
      constipation; all except Sweden also had a diarrhea group. The cluster analysis
      yielded slightly more disparate results but a healthy group was present in all
      populations. All four populations had an IBS and/or bowel dysfunction cluster
      identified; a gastroesophageal reflux cluster was also present in all countries.
      CONCLUSIONS: The similarity of factor and cluster structures found in these four
      nations suggest that patterns of GI symptoms and groupings of individuals are
      similar across these Western cultures. These results are consistent with the
      current international Rome classification for separate upper and lower functional
      GI disorders.

PMID- 10894577
TI  - The proportion of upper gastrointestinal symptoms in the community associated
      with Helicobacter pylori, lifestyle factors, and nonsteroidal anti-inflammatory
      drugs. Leeds HELP Study Group.
AB  - OBJECTIVE: Upper gastrointestinal disorders are common in the community, yet the
      determinants of these symptoms are poorly characterized. The association between
      upper gastrointestinal symptoms and Helicobacter pylori (H. pylori),
      socioeconomic status, nonsteroidal antiinflammatory drug (NSAID) use, smoking,
      alcohol, and coffee intake was assessed in a cross-sectional survey. METHODS:
      Subjects between the ages of 40-49 yr were randomly selected from the lists of 36
      primary care centers. Participants attended their local primary care center and
      were interviewed by a researcher using a validated dyspepsia questionnaire. H.
      pylori status was determined by a nonfasting 13C-urea breath test. RESULTS: A
      total of 32,929 subjects were invited, and 8,407 (25%) attended and were
      eligible. Of these, 2,329 (28%) were H. pylori positive and 3,177 (38%) had
      dyspepsia. Also, 44% of H. pylori-infected participants reported dyspepsia
      compared with 36% of uninfected subjects [odds ratio = 1.39; 95% confidence
      interval (CI) 1.26-1.53]. H. pylori infection remained a significant risk factor
      for dyspepsia in a multiple logistic regression model (odds ratio = 1.21; 95% CI
      1.09-1.34), suggesting that 5% of dyspepsia in the population is attributable to
      H. pylori. NSAIDs, low educational attainment, renting accommodation, absence of
      central heating, sharing a bed with siblings, and being married were also
      significantly associated with dyspepsia in this model. Smoking, but not drinking
      alcohol or coffee, was marginally associated with dyspepsia, but this finding was
      not robust. These factors were not associated with any dyspepsia subtype.
      CONCLUSIONS: H. pylori is significantly associated with dyspepsia and may be
      responsible for 5% of upper gastrointestinal symptoms in the community.

PMID- 10894578
TI  - Assessment of gastric emptying using a low fat meal: establishment of
      international control values.
AB  - OBJECTIVE: The diagnosis of gastroparesis implies delayed gastric emptying. The
      diagnostic gold standard is scintigraphy, but techniques and measured endpoints
      vary widely among institutions. In this study, a simplified scintigraphic
      measurement of gastric emptying was compared to conventional gastric
      scintigraphic techniques and normal gastric emptying values defined in healthy
      subjects. METHODS: In 123 volunteers (aged 19-73 yr, 60 women and 63 men) from 11
      centers, scintigraphy was used to assess gastric emptying of a 99Tc-labeled low
      fat meal (egg substitute) and percent intragastric residual contents 60, 120, and
      240 min after completion of the meal. In 42 subjects, additional measurements
      were taken every 10 min for 1 h. In 20 subjects, gastric emptying of a 99Tc
      labeled liver meal was compared with that of the 99Tc-labeled low fat meal.
      RESULTS: Median values (95th percentile) for percent gastric retention at 60,
      120, and 240 min were 69% (90%), 24% (60%) and 1.2% (10%) respectively. A power
      exponential model yielded similar emptying curves and estimated T50 when using
      images only taken at 1, 2 and 4 h, or with imaging taken every 10 min. Gastric
      emptying was initially more rapid in men but was comparable in men and women at 4
      h; it was faster in older subjects (p < 0.05) but was independent of body mass
      index. CONCLUSIONS: This multicenter study provides gastric emptying values in
      healthy subjects based on data obtained using a large sample size and consistent
      meal and methodology. Gastric retention of >10% at 4 h is indicative of delayed
      emptying, a value comparable to those provided by more intensive scanning
      approaches. Gastric emptying of a low fat meal is initially faster in men but is
      comparable in women at 4 h; it is also faster in older individuals but is
      independent of body mass.

PMID- 10894579
TI  - Safety and efficacy of digital rectal examination in patients with acute
      myocardial infarction.
AB  - OBJECTIVE: Digital rectal examination (DRE) is often ignored or deferred in acute
      myocardial infarction (AMI). The aim of this study was to determine the safety
      and efficacy of DRE in patients with AMI. METHODS: This was a prospective,
      comparative, stratified study in an inner-city teaching hospital. A total of 480
      patients from intensive care and telemetry units were stratified into three
      groups. Group I included 160 patients with AMI in whom a DRE was performed and
      electrocardiographic (EKG) recordings were obtained. Group II included 155
      patients with AMI in whom DRE was not done, but EKG recordings were made. Group
      III consisted of 165 patients without AMI in whom DRE was performed and EKG
      recordings were obtained. Sustained arrhythmias and vital signs were measured.
      RESULTS: None of the patients developed sustained arrhythmias and there was no
      change in vital signs. DRE resulted in the detection of several clinically
      significant findings. CONCLUSION: DRE was found to be safe in our stable patients
      with AMI.

PMID- 10894580
TI  - Is endoscopic drainage of common bile duct stenoses in chronic pancreatitis up-to
      date?
AB  - OBJECTIVE: Common bile duct (CBD) stenoses often complicate chronic pancreatitis
      (CP). Although endoscopic drainage is employed as a standard procedure in
      malignant CBD stenoses, it is not yet the approved standard therapy of CBD
      stenosis in CP. METHODS: The records of 31 patients with CBD stenosis in CP who
      had undergone endoscopic placement of plastic endoprostheses into the bile duct
      between January 1991 and February 1997 were analyzed retrospectively. In all, 18
      patients suffered from jaundice and 13 patients exclusively showed serological
      cholestasis. Upstream dilation of the CBD (19 +/- 6.6 mm, 12-35 mm) was detected
      by ERCP in all patients. In total, 101 endoprostheses were implanted
      endoscopically, exchanged after 3 +/- 2 months, and removed after 10 +/- 8
      months. RESULTS: All jaundiced patients showed immediate improvement of
      cholestasis after drainage. At the time of last exchange or after stent removal,
      prestenotic CBD dilation was reduced in 55% of all patients. Complete regression
      of stenosis and prestenotic dilation was accomplished only in 13%; dilation
      remained unchanged in 10%, and even showed progression in 22%. A total of 29
      patients were followed-up over 24 months. Cholestatic parameters remained normal
      in all patients with complete normalization of the CBD, and were only moderately
      increased in another 10 patients, 7 and 28 months after stent removal,
      respectively. CONCLUSIONS: Technical and immediate clinical success of CBD
      stenting in patients with CBD stenoses due to CP is high; however, long-term
      complete normalization of the bile duct is rare. Endoscopic drainage of CBD
      stenosis in patients with CP can be recommended to alleviate acute cholestasis,
      but not yet as a definite treatment.

PMID- 10894581
TI  - Survival analysis in percutaneous endoscopic gastrostomy feeding: a worse outcome
      in patients with dementia.
AB  - OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) feeding has been validated
      in specific clinical situations such as acute stroke with dysphagia and
      oropharyngeal malignancy. The perception that gastrostomy insertion is safe and
      technically simple has led to an increase in the demands for PEG insertion,
      encompassing clinical applications such as in patients with dementia, in whom its
      role has not been justified. The purpose of this study was to compare the
      mortality of patients with dementia who were fed by PEG to that of other
      subgroups of patients requiring gastrostomy feeding. METHODS: The study focused
      on a cohort of 361 consecutive patients requiring PEG feeding between August 1992
      and July 1997 from two District General Hospitals (Rotherham District General
      Hospital and Doncaster Royal Infirmary) in South Yorkshire. A retrospective
      cohort survival analysis was performed using the Kaplan-Meier survival method and
      Cox proportional hazards analysis. RESULTS: In all patients requiring gastrostomy
      feeding there is a high initial mortality of 28% at 30 days. However, patients
      with dementia have a worse prognosis compared to other subgroups, with 54% having
      died at 1 month and 90% at 1 yr (log rank test p < 0.0001). This difference
      remained significant (log rank p < 0.0001) after adjusting for age at the time of
      PEG insertion. CONCLUSIONS: This is the first demonstration in the United Kingdom
      that the mortality of patients with dementia who are fed by gastrostomy is
      considerable. Consequently, we may wish to advise against gastrostomy feeding in
      selected patients within this clinical setting.

PMID- 10894582
TI  - Propofol versus midazolam and meperidine for conscious sedation in GI endoscopy.
AB  - OBJECTIVE: Propofol (2,6-diisopropyl phenol) is a relatively new intravenous
      sedative hypnotic with an ideal pharmacokinetic profile for conscious sedation.
      In this study, we compared the safety and efficacy of propofol versus the
      conventional regimen of midazolam and meperidine for conscious sedation in GI
      endoscopy. METHODS: In this prospective study, 274 patients that included many
      elderly patients with multiple comorbid conditions underwent GI endoscopic
      procedures at our hospital. A total of 150 patients received propofol (20-120 mg)
      and fentanyl (0.25-1.5 mg). The control group of 124 patients was given midazolam
      (2-6 mg) and meperidine (25-75 mg). The dose of medication was titrated according
      to patient need and the duration of the procedure. A "comfort score" on a scale
      of 1-4 assessed the efficacy of the drugs based on pain or discomfort to the
      patient and ease of endoscopy. A "sedation score" was used to assess the degree
      of sedation on a scale of 1-5. The Aldrete score was used to measure recovery
      from anesthesia at 5 and 10 min after the procedure. RESULTS: After controlling
      for age, American Society of Anesthesiologists' Physical Status Classification
      (ASA grade), and type and duration of procedure, logistic regression analysis
      determined that propofol resulted in 2.04 times better patient comfort (p =
      0.033, 95% CI = 1.058-3.923). Propofol was 1.84 times more likely to produce
      deeper sedation than the regimen of midazolam and meperidine (p = 0.027, 95% CI =
      1.071-3.083). The recovery from sedation was faster in patients receiving
      propofol, although this did not reach statistical significance. The safety
      parameters between the two groups were comparable. CONCLUSION: Propofol was
      associated with a statistically significant improvement in comfort and sedation
      score when compared to midazolam and meperidine.

PMID- 10894583
TI  - Early measles virus infection is associated with the development of inflammatory
      bowel disease.
AB  - OBJECTIVE: The measles virus has been implicated as a possible etiological agent
      in the development of inflammatory bowel disease (IBD). Measles infection at an
      early age is associated with subacute sclerosing panencephalitis, a degenerative
      neurological condition caused by persistent measles infection of the central
      nervous system. We sought to determine whether infection with measles virus at an
      early age was also associated with an increased risk of developing IBD. METHODS:
      Patients with measles infection diagnosed before the age of 5 yr were identified
      through the diagnostic indices of the Mayo Clinic and the Rochester Epidemiology
      Project. A questionnaire was used to ascertain a subsequent history of IBD, which
      was confirmed by records from the subjects' physicians. The risks of developing
      Crohn's disease and ulcerative colitis were calculated relative to expected rates
      for these conditions in the Olmsted County, Minnesota population. RESULTS: Of
      1164 eligible cases, 662 (57%) completed the questionnaire. There were six
      confirmed cases of Crohn's disease and six of ulcerative colitis. The expected
      number of cases was 1.9 for Crohn's disease (standardized incidence ratio [SIR]
      3.1, 95% confidence interval [CI] 1.1-6.8) and 2.0 for ulcerative colitis (SIR
      3.0, CI 1.1-6.5). There was a trend towards a higher risk of developing IBD with
      an earlier age of infection. CONCLUSIONS: Early measles infection is associated
      with an increased risk of developing Crohn's disease and ulcerative colitis. The
      risk may be higher with earlier infection.

PMID- 10894584
TI  - Anastomotic configuration and mucosal 5-aminosalicyclic acid (5-ASA)
      concentrations in patients with Crohn's disease: a GISC study. Gruppo Italiano
      per lo Studio del Colon e del Retto.
AB  - OBJECTIVE: Recurrence of Crohn's disease quite inevitably occurs after resection
      of distal small bowel and proximal colon, involving the neoterminal ileum close
      to the anastomosis. Oral 5-aminosalicylic acid (5-ASA) administered soon after
      surgery delays recurrence and reduces its severity. We recently observed that in
      operated patients submitted to prophylactic treatment with oral 5-ASA the rate of
      recurrence was significantly higher in those with end-to-end anastomosis than in
      those with other types of anastomosis (end-to-side, side-to-side). The hypothesis
      investigated in the present study was that patients with end-to-side or side-to
      side anastomosis would benefit from a higher mucosal concentration of 5-ASA with
      respect to patients with end-to-end anastomosis. Therefore, the mucosal 5-ASA
      concentration was measured in the perianastomotic area of both groups. METHODS:
      The study was carried out in 19 patients submitted to radical surgery for Crohn's
      ileitis or ileocolitis, under oral prophylactic treatment with 5-ASA (Asacol).
      All patients were on regular endoscopic follow-up and were free of recurrence.
      Two biopsies were collected 3 cm from the anastomosis, in the neoterminal ileum,
      and two biopsies were collected at the colonic site 3 cm below the anastomosis. 5
      ASA concentrations (ng/mg) were measured in tissue homogenates by high
      performance liquid chromatography (HPLC) with electrochemical detection. RESULTS:
      The mucosal concentration of 5-ASA in the neoterminal ileum was significantly
      lower in patients with end-to-end anastomosis than in those with other types of
      anastomosis (median values: 29.4 ng/mg vs 92.9 ng/mg respectively; p < 0.001).
      Six of 10 patients (60%) with end-to-end anastomosis, but none of the nine
      patients with other types of anastomosis, showed 5-ASA mucosal concentrations <40
      ng/mg at the neoterminal ileum. On the contrary, no patients with end-to-end
      anastomosis showed mucosal concentrations of 5-ASA >90 ng/mg, compared with the
      57% of patients in the group with other types of anastomosis. No differences were
      observed for colonic biopsies. CONCLUSIONS: The different mucosal concentrations
      in these two groups may be explained by the difference in segmental transit time
      induced by the different anastomotic configurations. A slower preanastomotic
      transit time, demonstrated in patients with end-to-side or side-to-side
      anastomosis, could offer a prolonged contact time between the intestinal content
      and the mucosa, resulting in an increase in drug absorption.

PMID- 10894585
TI  - Bone mineral density and body composition in patients with ulcerative colitis.
AB  - OBJECTIVE: Reduced bone mineral density (BMD) has been reported in ulcerative
      colitis (UC) patients, but body composition (fat and lean mass) has never been
      concomitantly studied. We sought to investigate BMD and body composition in a
      group of UC outpatients with the following characteristics: age 18-60 yr (men)
      and 18-45 yr (women); no intestinal resection; no immunosuppressive treatment;
      and regular menstruation. METHODS: Whole body and subregional BMD and body
      composition in 43 UC patients (21 men, 22 women; male mean age, 36.5 [21-57] yr;
      female mean age, 35.3 [23-45] yr) and 121 healthy volunteers were studied by
      means of dual X-ray photon absorptiometry. RESULTS: There were no differences in
      total and subregional BMD, or fat and lean mass between the patients and
      controls, except that the total and trunk lean mass of the UC women was lower
      than that in the normal controls. No correlation was found between lifetime
      steroid intake and BMD. CONCLUSIONS: UC outpatients do not differ from normal
      subjects in terms of BMD and fat mass. Mild and moderate UC does not represent a
      risk factor for osteopenia.

PMID- 10894586
TI  - Phagocytosis, killing, lymphocyte-mediated antibacterial activity, serum
      autoantibodies, and plasma endotoxins in inflammatory bowel disease.
AB  - OBJECTIVE: Alteration of mucosal and systemic immune responses may play an
      important role in the pathogenesis of inflammatory bowel disease (IBD). The aim
      of this study was to evaluate natural immune responses (i.e., phagocytosis,
      killing, and antibacterial activity), serum autoantibodies (antineutrophil
      cytoplasmic antibodies [ANCA] and anti-lactoferrin [LF] antibodies), and plasma
      endotoxins in patients affected by ulcerative colitis (UC) and Crohn's disease
      (CD). METHODS: Blood samples were obtained from 71 patients with UC, 32 patients
      with CD, and 32 control subjects. Disease activity was scored using Truelove's
      criteria in patients with UC and the Crohn's Disease Activity Index (CDAI) in
      patients with CD. Candida albicans served as a target for evaluation of
      phagocytosis and killing exerted by polymorphonuclear cells (PMN) and monocytes
      (MO), whereas Salmonella typhi was used for assessing lymphocyte-mediated
      antibacterial activity. ANCA were detected by indirect immunofluorescence,
      whereas anti-LF antibodies were assayed by means of enzyme-linked immunosorbent
      assay. Plasma endotoxins were measured by Limulus amoebocyte lysate assay.
      RESULTS: Phagocytosis and killing exerted by PMN and MO, as well as lymphocyte
      mediated antibacterial activity, were significantly reduced (p < 0.0001) in
      patients affected by UC and CD in comparison with controls, irrespective of
      either disease activity or treatment. Plasma endotoxins were detected in 12/71
      (17%) patients with UC, and in 10/32 (31%) patients with CD. ANCA were present in
      42/71 (59%) patients with UC and in 3/32 (9%) patients with CD, whereas anti-LF
      antibodies were detected in 31 (44%) UC patients and in six (19%) CD patients. No
      significant differences in phagocytosis and killing exerted by PMN were found
      between ANCA-positive and ANCA-negative UC patients. CONCLUSIONS: Our data
      demonstrate an impairment of natural immunity exerted by peripheral blood
      phagocytes and lymphocytes in patients with UC and CD. ANCA and anti-LF
      antibodies were present mainly in UC patients but their presence did not affect
      PMN-mediated phagocytosis and killing. Finally, plasma endotoxins may contribute
      to the chronic inflammatory status, likely by inducing release of proinflammatory
      mediators.

PMID- 10894587
TI  - Gluten sensitivity in monozygous twins: a long-term follow-up of five pairs.
AB  - OBJECTIVE: The aim of this study was to investigate the role of genetic factors
      and the characteristics of five monozygous twin pairs with at least one member
      affected by gluten sensitivity. METHODS: Five pairs of monozygous female twins,
      of whom one or both were affected by gluten sensitivity (i.e., celiac disease or
      dermatitis herpetiformis), were followed-up for 11-23 yr. RESULTS: Three pairs
      were concordant for celiac disease: the onset was comparable and synchronous in
      two pairs; in the third, one member presented an overt malabsorption syndrome,
      and the other developed iron deficiency anemia 10 yr later. Discordance for
      gluten sensitivity was found in the remaining two pairs, one of whose members was
      diagnosed as having, respectively, celiac disease and dermatitis herpetiformis.
      CONCLUSIONS: As no environmental factors were found to affect the phenotypic
      expression of the disease, genetic factors seem to play a major role. The
      presence of overt or latent celiac disease in three of the four siblings of the
      three concordant twins, and the association with cystic fibrosis in all three
      siblings of one of these families, further supports this hypothesis.

PMID- 10894588
TI  - Isolated intestinal transplantation for intestinal failure.
AB  - OBJECTIVE: Parenteral nutrition sustains life in patients with intestinal
      failure. However, some experience life-threatening complications from parenteral
      nutrition, and in these individuals intestinal transplantation may be lifesaving.
      METHODS: This is a retrospective review of 28 consecutive isolated small bowel
      transplants performed in eight adults and 20 children between December 1993 and
      June 1998 at the University of Nebraska Medical Center. RESULTS: The 1-yr patient
      and graft survivals were 93% and 71%, respectively. The causes of graft loss were
      hyperacute rejection (n = 1), acute rejection (n = 5), vascular thrombosis (n =
      1), and patient death (n = 1). The median length of time required until full
      enteral nutrition was 27 days. All 28 patients have experienced acute rejection
      of their small bowel grafts and rejection led to graft failure in five. Jaundice
      and/or hepatic fibrosis was present preoperatively in 17 of the 28 recipients and
      hyperbilirubinemia was completely reversed in all patients with functional grafts
      within 4 months of transplantation. Three patients developed post-transplant
      lymphoproliferative disease (11%). Three recipients developed cytomegalovirus
      enteritis and all were successfully treated. CONCLUSIONS: Patient survival after
      intestinal transplantation is comparable to parenteral nutrition for patients
      with intestinal failure. Better immunosuppressive regimens are needed to decrease
      the risk of graft loss from acute rejection. The incidence of posttransplant
      lymphoproliferative disorder is higher after intestinal transplantation than
      after other solid organ transplants and the risk of cytomegalovirus enteritis is
      low with the use of cytomegalovirus seronegative donors. Liver dysfunction in the
      absence of established cirrhosis can be reversed.

PMID- 10894589
TI  - An increased number of CD40-high monocytes in patients with Crohn's disease.
AB  - OBJECTIVE: CD40-CD40 ligand (CD40L) interaction is essential for the T-lymphocyte
      dependent immune response. This interaction may be operational in the
      pathogenesis of inflammatory bowel diseases (IBD). The present study examined the
      expression of CD40 in peripheral blood mononuclear cells (PBMNCs) and tissue
      specimens, and CD40-stimulated interleukin (IL)-12 release from PBMNCs in IBD.
      METHODS: The expression of CD40 in PBMNCs and tissue inflammatory cells was
      examined by flowcytometry and immunohistochemistry, respectively. IL-12 release
      was measured in cultured media of PBMNCs by an enzyme-linked immunosorbent assay.
      RESULTS: Most peripheral blood B-lymphocytes expressed CD40 in all subjects.
      However, in ulcerative colitis (UC) patients, a significantly increased mean
      fluorescence intensity (MFI) of CD40 on B-lymphocytes was detected, compared with
      control subjects and patients with Crohn's disease (CD). In contrast, both the
      percentage positivity and MFI of CD40 on monocytes of active CD subjects were
      significantly increased, compared with the other groups. In active CD patients, a
      high level of IL-12 release from PBMNCs was observed by CD40 stimulation,
      compared with those of the other groups. When primed with IFN-gamma, PBMNCs from
      inactive CD patients released a significantly high level of IL-12, probably via
      stimulation by the CD40 monoclonal antibody. In the affected mucosa of CD,
      numerous CD40-positive cells were demonstrated, and they were also CD68-positive,
      suggesting these double CD40/ CD68-positive cells are tissue macrophages.
      CONCLUSIONS: These results suggest that the examination of CD40 expression in
      PBMNCs might enable the differentiation of CD from UC. CD40-high monocytes in CD
      patients may play a role in the pathogenesis of CD.

PMID- 10894590
TI  - Cost-effectiveness of 24 or 48 weeks of interferon alpha-2b alone or with
      ribavirin as initial treatment of chronic hepatitis C. International Hepatitis
      Interventional Therapy Group.
AB  - OBJECTIVE: Initial therapy with ribavirin and interferon alpha-2b results in a
      higher sustained virological response than interferon alone, but this regimen is
      expensive. We aimed to examine the cost-effectiveness of 24- or 48-wk initial
      treatment with combination therapy versus interferon alone for patients who have
      chronic hepatitis C. METHODS: Data from recent randomized clinical trials
      comparing combination therapy to interferon alone were applied to a previously
      published computer cohort simulation to project lifelong clinical and economic
      outcomes. Natural history and economic estimates were based on published
      literature, expert panel estimates, and actual variable cost and reimbursement
      data. RESULTS: Using treatment stopping rules, sustained viral negative response
      rates would be 33.1% and 39.8% for patients receiving 24 versus 48 wk of
      ribavirin/interferon, compared with 14.3% for 48 wk of interferon alone. Compared
      to the interferon alone strategy, 24 or 48 wk of combination therapy should
      prolong life expectancy by 1.4 to 2.0 yr at marginal cost-effectiveness ratios of
      $4,400 to $5,400 per discounted quality-adjusted life-year (DQALY) gained.
      Compared to 24 wk of combination therapy, 48 wk of combination therapy should
      prolong life expectancy by 0.6 yr at a marginal cost-effectiveness ratio of
      $7,700 per DQALY gained. The results were robust, with 24 or 48 wk of combination
      therapy remaining preferred and cost-effective in sensitivity analysis compared
      with interferon alone. CONCLUSION: For patients with chronic hepatitis C, 24 or
      48 wk of ribavirin and interferon should prolong life and be cost-effective when
      compared with 48 wk, of interferon alone.

PMID- 10894591
TI  - Alpha-1 antitrypsin deficiency and splenic artery aneurysm rupture: an
      association?
AB  - OBJECTIVE: Theoretically, patients with alpha 1-antitrypsin deficiency may be
      vulnerable to the development of splenic artery aneurysms. alpha-1 antitrypsin
      deficiency can induce cirrhosis with portal hypertension, and resulting protease
      antiprotease imbalances may exaggerate arterial wall weakness due to proteolysis
      of arterial structural proteins. A splenic artery aneurysm rupture 7 days after
      liver transplantation provoked a reassessment of the incidence of this phenomenon
      in a liver transplant population. METHODS: Case records from three institutions
      and the results of a survey sent to 126 liver transplantation programs in the
      United Network for Organ Sharing database were reviewed. The incidence of splenic
      artery aneurysm rupture in the peritransplantation period, etiology of liver
      disease associated with this phenomenon, and recommendations regarding management
      of splenic artery aneurysms was assessed. RESULTS: Twenty-one cases of splenic
      artery aneurysm rupture were identified. alpha-1 antitrypsin deficiency was the
      most common cause of cirrhosis in the majority of identified patients who
      presented with splenic artery aneurysm rupture, which was associated with a
      mortality rate of 57%. Respondents to the survey indicated that a preoperative
      evaluation was warranted if a splenic artery aneurysm was suspected; however, no
      consensus regarding management exists. CONCLUSIONS: The presence and risk of
      rupture of splenic artery aneurysms may be greater in patients with alpha-1
      antitrypsin deficiency. If identified before rupture, an aggressive approach to
      diagnosing and treating these aneurysms should be initiated. At present, no
      consensus exists regarding the management of splenic artery aneurysms.

PMID- 10894592
TI  - Sensitivity of commonly available screening tests in detecting hepatocellular
      carcinoma in cirrhotic patients undergoing liver transplantation.
AB  - OBJECTIVE: Recognition of hepatocellular carcinoma (HCC) is important in the
      management of patients awaiting liver transplantation. HCCs >5 cm in diameter are
      at high risk to recur after transplant. The goal of this study was to assess the
      sensitivity of the diagnostic tests employed in a pretransplant screening
      program. METHODS: The study is a retrospective analysis of charts of 106
      consecutive adults transplanted over a 1-yr period. All patients had
      ultrasonography (US), computerized tomography (CT), and serum alpha fetoprotein
      (AFP) testing within 6 months of transplantation. Radiographic reports were
      subdivided into low-risk and high-risk groups, based upon level of suspicion for
      HCC. The results were compared to explant pathology. RESULTS: Pathological
      analysis of 106 explants revealed HCC in 19 patients. High-risk US exams had a
      positive predictive value (PPV) of 0.69 and a negative predictive value (NPV) of
      0.91 in the diagnosis of HCC. High-risk CT exams had a PPV of 0.67 and an NPV of
      0.90. When patients had either a high-risk US or a high-risk CT, there was a PPV
      of 0.59 and an NPV of 0.83. Of the 19 patients with HCC, three had high-risk US
      and low-risk CT; two had high-risk CT and low-risk US. Four patients, all with
      HCC <4 cm, had low-risk US, CT, and serum AFP. CONCLUSIONS: US, CT, and serum
      AFP, as single tests, are insensitive for detection of HCC in the cirrhotic
      liver. However, they are highly specific. Sensitivity and specificity for US are
      comparable to those for CT. Given its lower cost, US is preferable to CT for
      routine screening of HCC in patients with end-stage liver disease undergoing
      liver transplantation.

PMID- 10894593
TI  - Nitric oxide may contribute to nocturnal hemodynamic changes in cirrhotic
      patients.
AB  - OBJECTIVE: Patients with liver cirrhosis have a nocturnal worsening of
      hemodynamic parameters that has been associated with an increased risk of
      variceal bleeding at nighttime. The aim of this study was to investigate whether
      nitric oxide and cytokines are implicated in these hemodynamic changes. METHODS:
      Ten cirrhotic patients and eight controls were studied. Mean blood pressure,
      heart rate, plasma norepinephrine, tumor necrosis factor alpha and interleukin-6
      levels, and serum nitrite + nitrate levels were determined at 0800, 1600, and
      2400 h. All determinations were performed in supine rest and at least 4 h after
      meals. In a second study, nitrite + nitrate levels were assessed in 10 cirrhotic
      patients before and after eating a standard meal. RESULTS: Mean arterial pressure
      levels that were always lower in the patient group showed a nocturnal decrease in
      both groups of subjects. Heart rate values that were always higher in cirrhotic
      patients showed a nocturnal fall in controls, whereas cirrhotics maintained
      elevated values at nighttime. Norepinephrine levels were higher in cirrhotics and
      maintained similar values during the study, whereas controls had a significant
      nocturnal decrease. Nitrite + nitrate levels that were higher in cirrhotic
      patients showed a significant mean increase of 40% from morning (0800 h) to night
      (2400 h) in the patient group, whereas in controls no change was observed (p <
      0.05). Tumor necrosis factor alpha and interleukin-6 levels did not change either
      in patients or controls during the entire period. Cirrhotic patients with or
      without ascites maintained a pattern of hemodynamic and biochemical changes
      similar to the pattern observed in the entire group of patients. Finally, no
      changes in serum nitrite + nitrate levels were observed in patients before and
      after eating the standard meal. CONCLUSION: An increased nocturnal nitric oxide
      production might contribute to the hemodynamic changes observed in cirrhotic
      patients during nighttime.

PMID- 10894594
TI  - Serum aspartate but not alanine aminotransferase levels help to predict the
      histological features of chronic hepatitis C viral infections in adults.
AB  - OBJECTIVES: The aims of this study were to assess the predictive values of age,
      gender, route of transmission, extent of steatosis, alcohol consumption, and
      serum aminotransferase values on the histological findings in patients with
      chronic hepatitis C viral infections. METHODS: We retrospectively reviewed the
      charts and liver biopsy findings from 79 adult patients with serological evidence
      of chronic hepatitis C viral infections. RESULTS: The mean (+/- SD) age of the
      patient population was 43.5 +/- 10.8 yr; 47 patients (60%) were male. The routes
      of transmission were considered to be parenteral drugs in 44 patients (56%),
      previous blood transfusions in 25 (32%), and miscellaneous parenteral and
      nonparenteral routes in 10 (13%). The mean histological activity score of the
      group as described by Desmet et al. was 3.5 +/- 0.8 (maximum possible score, 18)
      and the fibrosis score 1.5 +/-0.4 (maximum possible score, 4), indicating
      relatively mild disease in the majority of cases. The extent of inflammation
      correlated with fibrosis (r = 0.72). By multivariate stepwise regression
      analyses, serum aspartate aminotransferase (AST) values emerged as the most
      important predictive variable of histological activity (r = 0.62). When overall
      histological activity was further divided into portal inflammation, piecemeal
      necrosis, and lobular activity, correlations were found between AST values and
      portal inflammation (r = 0.58) and piecemeal necrosis (r = 0.61) but not lobular
      activity (r = 0.1). A correlation was also observed between AST values and the
      extent of hepatic fibrosis (r = 0.64). On the other hand, serum ALT values did
      not correlate with histological activity but did correlate weakly with the extent
      of hepatic fibrosis (r = 0.39 and 0.51, respectively). There were no significant
      correlations between age, gender, route of transmission, steatosis, or alcohol
      consumption with the extent of histological activity or fibrosis. CONCLUSIONS:
      Serum AST values correlate well with two of three features of hepatic
      inflammation and with the extent of hepatic fibrosis. These findings suggest
      that, among other factors, serum AST values should be considered in decisions
      regarding the need for liver biopsy and treatment in patients with chronic
      hepatitis C viral infections.

PMID- 10894595
TI  - Colorectal cancer screening and surveillance practices by primary care
      physicians: results of a national survey.
AB  - OBJECTIVE: Screening for colorectal cancer reduces its morbidity and mortality
      and is cost-effective. Screening is usually the responsibility of primary care
      physicians who may be unsure about its implementation. We aimed to assess primary
      care physicians' knowledge and practice regarding colorectal cancer screening,
      and to compare their responses with those of three national experts and with
      published guidelines. METHODS: We mailed a postal questionnaire to 2,310 primary
      care physicians regarding demographics, nature of practice, use of screening
      tests, and six hypothetical patients who may have been candidates for screening
      or surveillance. We used published national guidelines and the collective
      opinions of the three external experts as the so-called "gold standard." RESULTS:
      Of all respondents, 85.1% offered colorectal cancer screening. Most used suitable
      tests, starting at an appropriate age; 49.8% continued screening indefinitely
      irrespective of patients' age and 43.6% performed fecal occult blood testing
      without appropriate dietary advice to patients. Also, respondents frequently
      performed this test for inappropriate indications. Only 51.8% would follow a
      positive fecal occult blood test with colonoscopy. CONCLUSIONS: Colorectal cancer
      screening practices by primary care physicians vary considerably from those
      recommended. Many offer screening to individuals in whom it is not appropriate,
      and continue it into advanced age. Frequent, inappropriate use of fecal occult
      blood tests will produce many false positives. Primary care physicians often do
      not appropriately follow a positive test. Further educational efforts are needed
      in an attempt to improve practice and further reduce the morbidity and mortality
      from colorectal cancer.

PMID- 10894596
TI  - Natural history of ampullary adenoma in familial adenomatous polyposis:
      reconfirmation of benign nature during extended surveillance.
AB  - OBJECTIVE: Surgical or endoscopic papillectomy may be one of the therapeutic
      strategies for patients with familial adenomatous polyposis (FAP). To determine
      whether prophylactic papillectomy is necessary for FAP, we investigated the
      natural history of the ampullary adenoma in FAP. METHODS: Eighteen subjects with
      FAP were surveyed by duodenoscopy with biopsy for >10 yr. Endoscopic appearance,
      histological findings, and immunohistochemical stainings for Ki-67 of ampulla
      were compared between initial and final endoscopic examinations. RESULTS: The
      endoscopic grade in the ampulla remained unchanged in 16 subjects, whereas in two
      subjects an increase in the endoscopic grade was noted. In two subjects adenoma
      developed from an endoscopically and histologically normal ampulla. The
      histological grade of dysplasia increased in three of 12 subjects who initially
      had adenoma. The labeling index for Ki-67 was not different between initial and
      final examinations. CONCLUSIONS: These data suggest that most ampullary adenoma
      of patients with FAP is static and that aggressive endoscopic or surgical removal
      is unnecessary for the adenoma.

PMID- 10894597
TI  - Resident participation in flexible sigmoidoscopy does not affect patient
      satisfaction.
AB  - OBJECTIVE: We sought to assess the effect of resident involvement in flexible
      sigmoidoscopy on patient satisfaction and comfort. METHODS: Adults undergoing
      flexible sigmoidoscopy completed a previsit questionnaire on indication for
      procedure, GI-related history, and functional status. Immediately after the
      procedure, satisfaction and procedure comfort were assessed. Additional
      information collected included procedure duration, depth of sigmoidoscope
      penetration, and visualization of diverticuli or polyps. RESULTS: Among 408
      endoscopies, patient characteristics and procedure indications were similar
      between sigmoidoscopies done by residents (n = 111) or staff. There were no
      differences in patient satisfaction, procedure comfort, or willingness to undergo
      the procedure again in the future. Sigmoidoscopies involving residents averaged
      5.6 min longer, even after adjusting for preparation quality, depth of insertion,
      specific endoscopist, and the presence of polyps or diverticuli. CONCLUSIONS:
      Patient satisfaction and comfort with flexible sigmoidoscopy was not reduced by
      resident involvement, though the procedure duration was slightly longer.

PMID- 10894598
TI  - Intrahepatic portal-hepatic venous anastomosis: a portal-systemic shunt with
      neurological repercussions.
AB  - Intrahepatic shunts are rarely diagnosed as a cause of neurocognitive
      abnormality. A complaint of fatigue led to the diagnosis of a right portal vein
      hepatic vein aneurysmal communication in a 23-yr-old, otherwise healthy woman.
      Neuropsychological testing, imaging, and MR spectroscopy revealed changes similar
      to those described in patients with cirrhosis and subclinical hepatic
      encephalopathy. T1-weighted MRI showed a hyperintense globus pallidus, a feature
      seen in subjects with and without portal-encephalopathy. Portal-systemic shunting
      in the absence of parenchymal liver disease reproduces neurological features
      described in cirrhosis.

PMID- 10894599
TI  - Multiple esophageal rings: an association with eosinophilic esophagitis: case
      report and review of the literature.
AB  - Esophagitis may present endoscopically with erythema, edema, loss of vascular
      pattern, friability, and ulceration of the esophageal mucosa. Left untreated,
      chronic esophagitis may result in stricture formation. The presence of multiple
      concentric rings involving the entire esophagus has been cited as a chronic form
      of esophagitis. We present a case of an 8-yr-old boy with multiple concentric
      esophageal rings and histological evidence of eosinophilic esophagitis, who
      failed medical antireflux treatment and responded to an elimination diet.

PMID- 10894600
TI  - Molecular and biological analysis of carcinoma of the small intestine: beta
      catenin gene mutation by interstitial deletion involving exon 3 and replication
      error phenotype.
AB  - The genetic mechanisms of carcinomas of the small intestine are not well
      understood. We report the results of analysis of genetic alterations in a case of
      small intestinal carcinoma. A tumor in the terminal ileum was resected in a 59-yr
      old woman. Histologically, the tumor was classified as well-differentiated
      adenocarcinoma. We screened for genetic alterations in adenomatous polyposis coli
      (APC), beta-catenin, K-ras, and p53 genes, as well as microsatellite instability,
      which are known to be involved in colorectal tumorigenesis. The tumor exhibited
      somatic interstitial deletion of 425-bp, which included the entire exon 3 in beta
      catenin gene. Immunohistochemical staining confirmed accumulation of aberrant
      beta-catenin protein in the cytoplasm and nuclei of the malignant tissue.
      Furthermore, a frameshift mutation in the transforming growth factor beta
      receptor type II gene with replication error phenotype was detected in the tumor
      DNA. In contrast, no genetic alterations were found in the APC, K-ras, and p53
      genes. Our results suggested that both beta-catenin gene mutation and replication
      error phenotype might contribute to carcinogenesis of the small intestinal tumor
      in our case. This is the first report that activation of beta-catenin gene by
      somatic gene mutation is involved in the development of carcinoma of the small
      intestine.

PMID- 10894601
TI  - Gastrointestinal bleeding from a Brunner's gland hamartoma: characterization by
      endoscopy, computed tomography, and endoscopic ultrasound.

PMID- 10894602
TI  - Nitric oxide--a major player in esophageal motility.

PMID- 10894603
TI  - Crohn's disease activity not affected by oral contraceptives.

PMID- 10894604
TI  - A surgical nirvana for GERD sufferers?

PMID- 10894605
TI  - Motility of the Roux-en-Y hepaticojejunostomy in asymptomatic patients.

PMID- 10894606
TI  - Re: Daniel et al.: liver biopsy without clear indication or informed consent.

PMID- 10894607
TI  - Congenital esophageal stenosis.

PMID- 10894608
TI  - Re: Van der Wouden et al.: the influence of in vitro nitroimidazole resistance on
      the efficacy of nitroimidazole-containing anti-Helicobacter pylori regimens.

PMID- 10894609
TI  - Severe gastrointestinal symptoms due to lead poisoning from Indian traditional
      medicine.

PMID- 10894610
TI  - Esophageal squamous-cell papillomatosis complicated by carcinoma.

PMID- 10894611
TI  - Hemorrhage related to an anal dieulafoy-like lesion.

PMID- 10894612
TI  - Endoscopic appendectomy in a case of appendicular intussusception due to
      endometriosis, mimicking a cecal polyp.

PMID- 10894613
TI  - Peptic ulcer or inflammatory gastric disease?

PMID- 10894614
TI  - Nefazodone-induced acute liver failure.

PMID- 10894615
TI  - Helicobacter pylori IgG antibody test established in the United States showed a
      substantially lower sensitivity for Japanese population.

PMID- 10894616
TI  - Tetany and profound diarrhea--a diagnostic combination you cannot miss.

PMID- 10894617
TI  - Immune thrombocytopenic purpura as the presenting feature of gastric MALT
      lymphoma.

PMID- 10894618
TI  - Endoscopic resection of early duodenal cancer using a strip biopsy technique.

PMID- 10894619
TI  - A pitfall of MRCP for preoperative cholangiography: report of a case.

PMID- 10894620
TI  - Arsenic and portal hypertension.

PMID- 10894621
TI  - Modification of controlled radial expansion balloon catheter to fit into Pentax
      diagnostic gastroscope.

PMID- 10894622
TI  - Fatal subfulminant hepatic failure with ofloxacin.

PMID- 10894623
TI  - Severe rectal bleeding due to leech bite.

PMID- 10894624
TI  - Paraganglioma of the gallbladder: report of a rare case.

PMID- 10894625
TI  - The channel occlusion technique: a novel method of retrieving polyps following
      snare resection.

PMID- 10894626
TI  - Optimized PCR assay for the detection of TT virus.
AB  - A polymerase chain reaction (PCR)-based procedure for the detection of TT virus
      DNA is described. In this method. total nucleic acid extracted from a small
      volume of serum or plasma is utilized as a template in PCR employing TT virus
      specific primers designed to highly conserved regions of the virus genome.
      Additional sensitivity is obtained by carrying out a second round of
      amplification. Reactions are analyzed by agarose gel electrophoresis, and samples
      having an ethidium bromide stainable fragment of the appropriate size in the
      first and/or second amplification are designated as positive. This protocol
      allows for the rapid and sensitive detection of TT virus in human plasma or
      serum.

PMID- 10894627
TI  - Standardisation of subjectively scored HIV immunoassays: developing a quality
      assurance program to assist in reproducible interpretation of results using an
      anti-HIV particle agglutination assay as a model.
AB  - Immunoassays such as particle agglutination assays, rapid tests and western or
      line blots are scored or read subjectively. These readings display intra- and
      inter-reader variability, as well as intra- and inter-laboratory variability. In
      the present study the consistency of scoring was assessed between readers both
      within and between two groups of scientists using the Serodia anti-HIV particle
      agglutination assay as an example of an assay scored subjectively. An anti-HIV
      positive sample in eight serial dilutions made to yield a full range of results
      expected for the assay was presented 12 times (96 test wells). Each dilution was
      placed randomly in a plate and tested with the Serodia anti-HIV particle
      agglutination assay then photographed. Participants in the two groups each scored
      the photographed plate independently and twice, 2 h apart. Each well was assigned
      a status (the consensus result of the four most experienced Australian readers)
      and each participant's results were compared with this status. The average
      percentage of wells assessed as 'correct' for the Group A participants was 86%
      (range 56-98%) and for the Group B participants was 67% 'correct' (range 46-88%).
      In general, strongly positive and negative wells were scored 'correctly'. The
      highest variations between scores were seen in the borderline positive dilutions
      +/- region. A quality assessment program based on the method used to obtain these
      results will be instituted in order to improve the consistency of scoring assays
      read subjectively.

PMID- 10894628
TI  - Development of the hot spot-combined PCR assay for detection of retroviral
      insertions into Marek's disease virus.
AB  - A two-step PCR, the Hot Spot-combined PCR assay, was developed for the
      identification and characterization of recombinant viruses in Marek's disease
      (herpes) and retrovirus co-infections. In the first PCR the herpesvirus genomic
      fragment, that was recognized in previous studies as a hot spot site for
      retroviral integration was amplified [reviewed in Bronovskis, P., Kung, H.-J.,
      1996. Retrotransposition and herpesvirus evolution. Virus Genes 11, 259-270]. The
      products served for a second amplification step, performed in six PCR sets, using
      the six possible combinations of the two herpes and the retrovirus primer sets.
      Development of the assay employed DNA of the recombinant virus, RM1, which was
      created by in vitro co-cultivation of Marek's disease and reticuloendotheliosis
      viruses [Isfort et al., 1992. Proc. Natl. Acad. Sci. 89, 991-995; Witter et al.,
      1997. Avian Dis. 41, 407-421]. As the retroviral insertion site and junction
      sequences were determined previously [Jones et al., 1996. J. Virol. 70, 2460
      2467], RMI served in the present study as a test virus for the development of the
      new assay. It is shown now that the Hot Spot-combined PCR can detect the
      retroviral insert in RM1. the MDV integration site and the insert orientation.
      For confirmation the herpes and retrovirus chimeric PCR products were sequenced
      and the results were similar to those published previously [Jones et al., 1996.
      J. Virol. 70, 2460-2467]. This assay might be adopted in additional systems to
      detect foreign inserts at suspected genomic sites.

PMID- 10894629
TI  - Rapid detection of specific polyclonal and monoclonal antibodies against bovine
      leukemia virus.
AB  - ELISA and Western blot have been used for detecting specific antibodies or
      antigens for routine diagnostic laboratory tests and experimental protocols, as
      well as for screening hybridomas secreting antibodies. Although these techniques
      are sensitive, some slow growing hybridomas are identified as positive only when
      they are grown slowly long time. We standardized the dot-ELISA, a more sensitive
      technique, for the detection of antibodies against BLV. The main advantages of
      the dot-ELISA described in this study are (a) its sensitivity, detecting
      hybridomas which would otherwise be considered negative and discarded from the
      results of indirect ELISA and/or Western blot; and (b) the possibility of
      economizing reagents using as little as 1 microl of the antigen and 0.5 microl of
      antibody and conjugate. Different BLV-antigen preparations were bound to
      nitrocellulose membranes (NC), including cells lysed chemically (LYS) or by
      sonication (SOC), semi-purified virus (PV), and supernatant from infected
      cultures, either without treatment (SUP) or sonicated (SOS). The antigen
      preparations most adequate for detecting monoclonal antibodies against BLV and
      polyclonal antibodies in cattle sera were undiluted cell lysates (LYS) and semi
      purified BLV (PV). When testing bovine sera, the supernatant (SUP) and sonicated
      supernatant (SOS) antigens gave a high background due to the presence of FCS
      which reacted with the anti-bovine labeled antibodies. In this study, 59 BLV
      specific antibody secreting hybridomas were identified using the dot-ELISA,
      compared to only 20 detected using iELISA, and doubtful reactions due to
      nonspecific binding to fetal calf serum (FCS) and cellular components were
      measured. The results of the improved dot-ELISA described may be stored at room
      temperature for future reference. Results were consistently reproducible in
      coated nitrocellulose membranes kept at different storage temperatures (-20
      degrees C, 4 degrees C, and 25-30 degrees C) 48 h, 1 week and 5 months.

PMID- 10894630
TI  - Multiplex polymerase chain reaction for the simultaneous detection and typing of
      polyomavirus JC, BK and SV40 DNA in clinical samples.
AB  - A novel multiplex nested PCR (nPCR) method was developed for detecting and
      differentiating simultaneously the DNA of polyomaviruses JC, BK and SV40 in a
      single tube. In the first amplification step the same set of primers were used to
      amplify a conserved DNA region of the large T antigen gene of JCV, BKV and SV40.
      The second round of multiplex nPCR was carried out using a set of primers
      designed to render products of different size for each related virus. The
      thermocycling parameters and concentration of each reaction component were
      optimised systematically to achieve optimal specificity and sensitivity for the
      nPCR assay. The sensitivity of the method ranged between one and 10 copies of
      polyomavirus genome. Cerebrospinal fluid (CSF) was examined from AIDS patients
      with clinical and neuroradiological evidence of progressive multifocal
      leukoencephalopathy (PML) and CSF from AIDS patients with other neurological
      alterations. Urine specimens from bone marrow transplant recipients affected by
      haemorrhagic cystitis were also tested. The results obtained suggest that the
      assay is a good tool for supporting the diagnosis of polyomavirus infection and
      could be used for epidemiological purposes and in other studies in order to
      define better the role of polyomaviruses in human disease.

PMID- 10894631
TI  - Development and evaluation of quantitative-competitive PCR for quantitation of
      coxsackievirus B3 RNA in experimentally infected murine tissues.
AB  - A method is described for quantitation of enterovirus RNA in experimentally
      infected murine tissues. Viral RNA was extracted from tissue samples and
      amplified by reverse transcriptase PCR in the presence of an internal standard
      RNA. The ratio of PCR product derived from viral RNA and internal standard RNA
      was then determined using specific probes in a post-PCR electrochemiluminescent
      hybridization assay. This provided an estimate of the viral RNA copy number in
      the original sample, and detection of PCR product derived from internal standard
      RNA validated sample processing and amplification procedures. RNA copy number
      correlated with viral infectivity of cell culture-derived virus, and one tissue
      culture infective dose was found to contain approximately 10(3) genome
      equivalents. The ratio of RNA copy number to infectivity in myocardial tissue
      taken from mice during the acute phase of coxsackievirus B3 myocarditis was more
      variable ranging from 10(4)-10(7), and was dependent on the stage of infection,
      reflecting differential rates of clearance for viral RNA and viral infectivity.
      The assay is rapid, and could facilitate investigations which currently rely upon
      enterovirus quantitation by titration in cell culture. This would be useful for
      experimental studies of viral pathogenesis, prophylaxis and antiviral therapy.

PMID- 10894632
TI  - RT-PCR and chemiluminescent ELISA for detection of enteroviruses.
AB  - Reverse transcription followed by polymerase chain reaction amplification (RT
      PCR) is now used commonly to detect the presence of enteric RNA viruses in
      environmental samples. A sensitive, non-isotopic microtitre plate hybridisation
      assay was developed and applied for detection of enteroviruses in environmental
      samples. Following reverse transcription, viral cDNA was labelled with
      digoxigenin (DIG)-dUTP during the PCR amplification step. The labelled PCR
      products were then hybridised with enterovirus-specific biotinylated
      oligonucleotide probe and captured in streptavidin-coated microtitre wells.
      Hybridised enteroviral PCR products were detected by an anti-digoxigenin
      peroxidase conjugate using either a colourimetric or a chemiluminescent substrate
      and automated measurement. Standard curves were established for poliovirus and
      other enteroviruses. The chemiluminescent assay was more sensitive than the
      colourimetric assay for detection of poliovirus, and was specific for
      enteroviruses. The chemiluminescent ELISA assay was used to confirm the presence
      of enteroviruses in environmental water samples.

PMID- 10894633
TI  - Simultaneous detection of five carnation viruses by non-isotopic molecular
      hybridization.
AB  - Several viruses, which in some cases can cause severe losses, affect carnation
      plants. These viruses include carnation mottle virus, carnation etched ring virus
      (CERV), carnation vein mottle virus, carnation ringspot virus, carnation Italian
      ringspot virus and carnation latent virus. A non-isotopic molecular hybridization
      was developed for the detection of these viruses in host plants and the
      sensitivity of the technique has been compared with enzyme-linked immunosorbent
      assay and bioassay methods. A procedure was developed to test simultaneously for
      the five RNA viruses (except CERV). The conditions established for this
      simultaneous detection did not include the DNA virus CERV due to the necessity of
      incorporating an additional step of RNase A treatment in the procedure to
      eliminate background signals. The sensitivity limits obtained for each virus
      using this multiple detection assay were identical to those obtained with the
      individual assays. The relative benefits of using this detection procedure for
      routine diagnosis of carnation viruses are discussed.

PMID- 10894634
TI  - Development of a blocking enzyme-linked immunosorbent assay for the serological
      diagnosis of chicken anaemia virus.
AB  - The development and evaluation of an enzyme-linked immunosorbent assay (ELISA)
      for the detection of serum antibody to chicken anaemia virus (CAV) are described.
      This test depends on the abilities of CAV-specific antibodies present in
      convalescent chicken serum to block the reaction between virus antigen, adsorbed
      to the ELISA plate. and a CAV-specific mouse monoclonal antibody (MAb), 2A9, that
      has been conjugated to horseradish peroxidase. The 2A9 MAb has been shown to
      react with 10 geographically different field isolates of CAV, a finding which
      indicates that the test will find worldwide application. In comparative
      experiments involving 525 serum samples from specific pathogen free and
      commercial breeder flocks, there was 98.5% agreement between the results obtained
      with the blocking ELISA and those obtained with an indirect ELISA developed
      previously in this laboratory. The blocking ELISA was found to have advantages in
      terms of speed and cost compared with the indirect ELISA format.

PMID- 10894635
TI  - High throughput detection of retrovirus-associated reverse transcriptase using an
      improved fluorescent product enhanced reverse transcriptase assay and its
      comparison to conventional detection methods.
AB  - The development and application of a novel, sensitive TaqMan fluorescent probe
      based product enhanced RT test (F-PERT) for the detection of retrovirus are
      described. The assay allows discrimination between the amplification signals
      generated by genuine positive signals that result from retroviral RT activity and
      the RT-like activity from DNA polymerases. The RT-like activity from DNA
      polymerases was suppressed by the addition of activated calf-thymus DNA with no
      reduction in the RT activity. A linear relationship between threshold cycle
      (C(T)) and the number of virus particles was demonstrated, allowing
      quantification of retroviruses in unknown samples. The F-PERT assay was able to
      detect a wide range of retroviral RT activities, including that from porcine
      endogenous retrovirus (PoERV), murine leukaemia virus (MLV), simian foamy virus
      (SFV), simian immunodeficiency virus (SIVmac) and squirrel monkey retrovirus
      (SMRV). The detection limit of SMRV, MLV and PoERV was approximately 100 virion
      particles and the test was able to detect at least 10(2) molecules of purified RT
      enzyme. RT activity was not detected in cellular lysates and supernatants from
      MRC-5, BT, VERO, or Raji cells, whereas RT activity was detected in C1271, Mus
      dunni, K-Balb, BHK-21, CHO-K1, SP2/0-Ag14 and NSO cell supernatants. RT activity
      was also detected in the Spodoptera cell line Sf9.

PMID- 10894636
TI  - Analysis of the viability of freezer stored serum samples for hepatitis C virus
      RNA analysis by the SUPERQUANT method: results of a 16 year retrospective study.
AB  - Prior to the discovery of the hepatitis C virus (HCV), virological analysis of
      serum from patients with non-A non-B hepatitis was not possible. Since the
      finding that HCV is the causative agent of most non-A non-B hepatitis, several
      reliable methodologies have been developed that allow for quantification of HCV
      RNA. To determine the viability of stored serum samples for HCV RNA analysis. 256
      samples were examined for HCV RNA using a multi-cycle RT-PCR assay. All samples
      were stored unopened in a -70 degree C freezer until the time of testing.
      Collection years ranged from 1981 to 1995. To examine the integrity of stored
      serum samples, the distribution of quantitative HCV RNA values for each year was
      compared: year-to-year; and, to the distribution of HCV RNA concentrations from
      1510 chronic HCV patients determined by the same assay in 1996 and 1997. Pairwise
      year-to-year analysis revealed that samples collected prior-to-and-including 1991
      had significantly lower HCV RNA concentrations as compared to samples collected
      after 1991 (P < 0.001). Likewise, comparison of the stored samples to the 1510
      fresh samples demonstrated that samples collected prior-to-and-including 1991 had
      significantly lower HCV RNA concentrations as compared to samples collected after
      1991 (P < 0.001). The results demonstrate a method for determination of the
      integrity of stored serum samples from chronic HCV patients. The mechanism of RNA
      degradation is unknown but it is most likely to be due to poor sample collection
      procedures in place prior to 1991.

PMID- 10894637
TI  - Challenges of the grounded theory approach to a novice researcher.
AB  - The grounded theory approach has been used in nursing research since 1970. The
      latest methodological books describe the research process in detail. However,
      there are many problems involved in the grounded theory approach, which
      especially need to be considered by a novice researcher. One of these problems is
      the question of how deeply and widely the researcher should familiarize her- or
      himself with the research topic before the empirical study. The problems also
      include the need to focus the research problem and to choose the sampling method.
      Data analysis is a multistage process, which demands from the researcher both
      sensitivity and time to work out the findings which emerge from the data. In this
      paper, the grounded theory approach is described as a process undertaken by the
      novice researcher. The purpose of this paper is to discuss the challenges of the
      grounded theory approach and the problems encountered by a researcher using the
      method for the first time.

PMID- 10894638
TI  - Parents associated with children in measuring acute and delayed nausea and
      vomiting.
AB  - The purpose of this study was to identify the relationship between parents and
      children in measuring children's acute and delayed nausea and vomiting induced by
      cancer chemotherapy. Twenty parent-child dyads participated in the study. Both
      instruments: Adapted Rhodes Index of Nausea and Vomiting by parent and by child
      (8-18 years old) were used every 12 h. The reliability and validity of these
      instruments have been established. There were significantly moderate to strong
      associations between parents and children in measuring these symptoms from Day 1
      to Day 3 (total scores: r = 0.85-0.93; nausea scores: r = 0.67-0.93; and vomiting
      scores: r = 0.91-0.99, all P < 0.01). Therefore, parents' observation of their
      children's symptoms was strongly associated with their child's self-report of
      symptoms. Parents were able to assess their children's acute and delayed nausea
      and vomiting because in this sample almost all parents accompanied their children
      all day long.

PMID- 10894639
TI  - Physical and psychological improvements after phase II cardiac rehabilitation in
      patients with myocardial infarction.
AB  - We have designed a new 4-week hospitalized phase II cardiac rehabilitation
      program. The purpose of the present study is to clarify whether the physical and
      psychological status of patients with myocardial infarction (MI) improves after
      participation in our program. Twenty-nine patients (27 males, two females) with
      acute MI who enrolled in the 4-week hospitalized phase II rehabilitation program
      were assessed. All patients enrolled in this study had received coronary
      interventions. The rehabilitation consisted of exercise training, education and
      counseling. We evaluated the physical and psychological status of the patients
      before and just after the program, and at a 6-month follow up. The physical
      status was assessed by exercise tolerance measured by the peak oxygen consumption
      and anaerobic threshold, frequency of exercise, and serum concentrations of
      triglyceride, total cholesterol, high-density lipoprotein-cholesterol, and low
      density lipoprotein-cholesterol. The psychological status was assessed by the
      Spielberger state-trait anxiety inventory questionnaire (STAI) and the self
      rating questionnaire for depression (SRQ-D). Thirty-four patients (27 men, seven
      women) with MI who did not participate in our rehabilitation program served as a
      control group. After participation in our rehabilitation program, exercise
      tolerance and the serum lipid profiles of the patients were improved compared
      with those before rehabilitation. These parameters had improved significantly 6
      months after rehabilitation. The STAI anxiety score was improved significantly
      and the SRQ-D depression score tended to be improved just after the
      rehabilitation program. Regular physical activity was continued even 6 months
      after the completion of the program. Our hospitalized phase II cardiac
      rehabilitation program improved the management of cardiac risk factors and the
      psychological status in patients with MI. This comprehensive program may
      contribute to the secondary prevention of MI as well as the recovery of physical
      and psychological activities.

PMID- 10894640
TI  - Participation in change: self-reflection of staff in a psychiatric admission
      unit.
AB  - This paper reports on a comprehensive nursing research and development project
      carried out in the psychiatric admission unit of The Mental Hospital, Keropudas,
      Finland. The purpose of the project was to plan, implement and evaluate the
      functioning of the ward in order to orient it more towards patient-centered
      practices. This study was an action research project, the methodological
      foundations of which were based on the action theory and dialectics. This article
      reports on the staff's written essays based on self-reflection concerning the
      orientation of action towards change. The essays were analyzed using the method
      of continuous comparison. This analysis yielded a conceptual outline of how the
      orientation of action towards change manifested itself in the internal regulation
      of the ward staff. The main category of data to result from selective coding was
      participation in change. Participation was enthusiastic, hesitant or withdrawn.

PMID- 10894642
TI  - Thoughts and feelings of in-patients with advanced terminal cancer: implications
      for terminal care improvement.
AB  - The purpose of this study was to clarify how terminally ill patients think and
      feel while hospitalized, thereby providing some insight into improving the
      quality of terminal care. The subjects of the study were eight terminally ill
      patients with cancer. The researchers obtained the patients' consent and their
      doctors' permission prior to conducting the interviews. Individual, semi
      structured interviews were conducted. The patients' thoughts and feelings were
      extracted and then categorized according to particular themes. As a result, we
      came up with four major categories: maintaining pain control, living an ordinary
      life, hoping for improvement of physical condition, and having family nearby. The
      desire to live life to its fullest given their situation, as well as to maintain
      a hopeful attitude about their future proved very important. The presence of
      family also played a crucial role. These factors must be taken into consideration
      in achieving better care for terminally ill patients.

PMID- 10894641
TI  - Japanese nurses' perceptions about disclosure of information at the patients' end
      of life.
AB  - Information disclosure at the end of life is one of the most debated ethical
      issues in Japan. This paper, using data from a larger questionnaire survey in
      which 147 Japanese nurses participated, describes nurses' perceptions about this
      issue. The nurses perceived that non-disclosure of impending death information to
      patients was the norm in Japan due to its traditional values. This non-disclosure
      of information has various impacts on clinical nurses. Tension was evident
      between the Japanese traditional concepts supported by some nurses and the shift
      toward Western cultural and ethical values supported by other nurses. The nurses
      confronted uninformed patients who became suspicious, isolated, angry, or died
      unprepared for their life's ending. The nurses were placed in the middle between
      the patient and the family, as nurses became keepers of family secrets, or
      between nurses' ethical obligations to the patient and those of the institution.
      The nurses had the belief that at the patient's end of life, it is important to
      change health professionals' attitude from curing to caring.

PMID- 10894643
TI  - Compliance of adolescents with asthma.
AB  - The purpose of this paper is to describe the health regimen compliance of
      adolescents with asthma and some factors related to it. The following research
      questions were addressed: (i) to what extent do adolescents with asthma comply
      with health regimens; and (ii) what type of factors are associated with
      compliance of adolescents with asthma? A total of 300 individuals aged 13-17
      years were randomly selected from the Finnish Social Insurance Institution's
      register. Every 15th person on the list was included in the sample and were sent
      questionnaires. A total of 88% (n = 266) of adolescents returned the
      questionnaire. The results showed that 42% of the adolescents with asthma
      complied fully with the health regimens, 42% placed themselves in the category of
      satisfactory compliance, and the remaining 18% reported poor compliance.
      Compliance with the need to avoid foods, animals and pollens that cause asthma
      attacks was poorest, while the highest degree of compliance was observed for
      medication and control visits to medical staff. Background variables, such as
      age, family size, exercise, smoking, alcohol intake and severity of disease, were
      significantly associated with compliance (P < 0.001). Good motivation, a strong
      sense of normality, energy and will-power, support from the parents, physicians
      and nurses, a positive attitude towards the disease and treatment, no threat to
      social wellbeing and no fears of complications had statistically significant
      relation to good compliance (P < 0.001).

PMID- 10894644
TI  - Exchanging knowledge.

PMID- 10894645
TI  - Nursing students' response to a case study in ethics.
AB  - This paper describes the responses of undergraduate nursing students to an
      ethical clinical case study. Students in a baccalaureate program were given a
      case study before a lecture on ethical principles and the same case study after
      this lecture. These responses raise questions about the content of nursing ethics
      classes in Japan. The place of individual patient rights and the role of the
      family in a situation of non-disclosure about diagnosis and prognosis were major
      issues for the students. The responses reveal the problem of the 'nurse-in-the
      middle' between the patient and others whose values differ. Students' post
      lecture responses emphasized communication among the people involved.

PMID- 10894646
TI  - Variations and inconsistencies in maternal and child health indicators in
      Ishikawa Prefecture, Japan.
AB  - As part of a community health assessment, variations in maternal and child health
      related vital statistics data in Ishikawa Prefecture, Japan, from 1984 to 1993
      were studied. Annual vital statistics reports published by the Prefectural
      government were used for the analysis. The following rates by public health
      district were calculated: abortion rate, early fetal mortality rate, late fetal
      mortality rate, perinatal mortality rate, neonatal mortality rate, and infant
      mortality rate. Maternal mortality rates were calculated for the Prefecture
      because of the small number of events. A few northern public health districts had
      relatively high perinatal mortality and infant mortality rates throughout the
      study period. Cause-specific infant mortality rates showed that the northern
      region had higher infant mortality rates related to the level of perinatal care,
      injury, and poisoning. Inconsistencies in the pattern of mortality were found in
      one of the 10 public health districts. No indirect maternal deaths were reported
      for the 10-year study period. This study identified potential problems for
      perinatal care in some districts. Results also suggest the potential
      misclassification of vital events, such as fetal deaths, induced abortions, and
      maternal deaths.

PMID- 10894647
TI  - Characteristics of the daily lives of elderly women at various facilities for the
      elderly.
AB  - A number of studies have been conducted about support for the daily lives of
      elderly individuals that will elevate their quality of life (QOL). Services
      provided to support these individuals have also become more diverse. This study
      will attempt to add to the understanding of QOL for the elderly by comparing
      levels of dependence and QOL of elderly women in four different types of
      institution. Individuals who were over 65 years of age and who were able to
      participate in a 1 h interview were chosen for this study. The subjects were
      selected from the elderly population of a hospital for aged patients, health
      service facilities for the elderly, a nursing home and a general hospital. Levels
      of dependency of activities of daily living (ADL) were measured using the Kahoku
      Aging Longitudinal Study Scale. The scale qualitatively evaluates the cognition
      and activities of the elderly. Each measure is rated on a four point scale.
      Quality of life was measured using the visual analogue scale. Elderly women
      living at the nursing home differed from those living in the other facilities in
      regard to their degree of independence in ADL and QOL. These findings indicate
      that there were differences in the characteristics of the daily lives of elderly
      women at different types of facilities.

PMID- 10894648
TI  - The measurement of stress in pregnancy.
AB  - Stress is thought to be one of the biopsychosocial factors that contribute to
      adverse pregnancy outcomes, such as preterm labor and low birthweight.
      Identification of these factors (as in total number), and measurement of their
      individually perceived importance (severity) could lead to opportunities for
      intervention, and improved pregnancy outcome. A pilot study of the Daily Hassles
      Scale, was conducted in order to determine the appropriateness of its use among
      pregnant women. Daily hassles were thought to be a valid proxy for prenatal
      stress. Content and construct validity were determined among a sample of four
      content experts and 30 pregnant women. The Daily Hassles Scale proved to be a
      reliable (internally consistent) measure of stress (alpha reliability coefficient
      of 0.90). Further adaptation of the scale to include hassles specific to
      pregnancy and further testing of its usefulness among diverse multicultural and
      ethnic populations is warranted.

PMID- 10894649
TI  - Development of an instrument to measure technological caring in nursing.
AB  - Twenty-seven statements make up the Technological Caring Instrument (TCI) which
      was developed to measure technological caring in nursing. In order to establish a
      database and its reliability and validity, responses were generated from 193
      professional nurses who participated in the study. The results indicate that the
      TCI has a high internal consistency, construct validity, and sufficient split
      half reliability. Cronbach's alpha was 0.8129 with split-half alpha of 0.666 for
      14 items in Part 1 and 0.828 for 13 items in Part 2. Significant differences were
      found between factors (F = 97.0199, P = 0.0000). Factor analysis identified eight
      items with the first factor revealing nine cluster statements with values of 0.51
      0.84. The second factor had two cluster statements with 0.75 and 0.74 values. The
      independent sample t-test results demonstrated the influence of education, area
      of expertise, and years of experience on the technological caring of registered
      professional nurses. The utilization and continued investigation of TCI are
      suggested.

PMID- 10894651
TI  - Healthcare system in Japan.
AB  - In Japan, each person is obligated to enroll in a national health insurance plan.
      Based on egalitarianism, the system is managed by the government and it finances
      almost the entire healthcare needs. However low the total healthcare expenditure
      in Japan is compared with other major countries, the statistics cause concern for
      the Japanese population for the future growth of its health care. Even though the
      Japanese healthcare system faces many problems at present, it provides everyone
      with a sense of security. The key to its success is the sense of and art of
      balance in healthcare policy making.

PMID- 10894650
TI  - Cross-cultural comparison of long-term psychiatric patients hospitalized in
      Tokyo, Japan and Honolulu, Hawaii.
AB  - The aim of this study is to cross-culturally explore the crucial and often
      conflicting issues of least restrictive placement of long-term psychiatric
      patients in Hawaii and Japan, and the need to provide high-quality care for such
      patients. Policy implications are discussed. A survey instrument facilitated the
      comparison of records from psychiatric patients hospitalized over 1 year in
      Hawaii, as of January 1993, and psychiatric patients hospitalized over 1 year in
      Japan, as of January 1996. The survey instrument was translated and validated for
      use in both countries. Interrater reliability averaged 0.96. The 30 subjects in
      Japan were all men (Japanese), and primarily unmarried. The 83 subjects in Hawaii
      were mostly men (Hawaiian or other ethnic minority), and unmarried. Subjects in
      Japan tended to be older, hospitalized longer, and were judged to be more
      dysfunctional than those in Hawaii. No significant relationship was revealed
      between nursing diagnoses and Axis I diagnoses in either sample. Although
      significant clinical differences were found between the two groups, the policy
      issues are similar: how to place patients in the least restrictive environment
      and how to provide high quality of care given the limited available resources.
      Nurses in both countries must become more vocal advocates for policy changes to
      improve the care of long-term patients.

PMID- 10894652
TI  - Coronary care nurses' clinical decision making.
AB  - Increasing acuity of hospitalized persons with cardiac disease places great
      demands on nurses' decision-making abilities. Yet nursing lags in knowledge-based
      system development because of limited understanding about how nurses use
      knowledge to make decisions. The two research questions for this study were: how
      do the lines of reasoning used by experienced coronary care nurses compare with
      those used by new coronary care nurses in a representative sample of hypothetical
      patient cases, and are the predominant lines of reasoning used by coronary care
      nurses in hypothetical situations similar to those used for comparable situations
      in clinical practice? Line of reasoning was defined as a set of arguments in
      which knowledge is embedded within decision-making processes that lead to a
      conclusion. Sixteen subjects (eight experienced and eight new nurses) from
      coronary care and coronary step-down units in a large, private, teaching hospital
      in Minnesota, USA, were asked to think aloud while making clinical decisions
      about six hypothetical cases and comparable actual case. One finding was that
      most subjects in both groups used multiple lines of reasoning per case; but they
      used only one predominantly. This finding highlighted the non-linear nature of
      clinical decision making. Subjects used 25 predominant lines of reasoning, with
      intergroup differences on six of them. Where there were differences, experienced
      nurses used lines of reasoning of lower quality than did new subjects. The type
      variability in lines of reasoning suggested that multiple pathways should be
      incorporated into knowledge-system design. One implication of the variability in
      subjects' line of reasoning quality is that nurses at all levels of expertise are
      fallible and could benefit from decision support. The finding that subjects
      tended to use similar lines of reasoning for comparable hypothetical and actual
      cases was modest validation of subjects' performance on hypothetical cases as
      representing their decision making in practice. Consequently, there was support
      for using simulations and case studies in teaching and studying clinical decision
      making.

PMID- 10894653
TI  - Coping and social support of parents with a diabetic child.
AB  - The purpose of this study is to describe and understand the parental coping and
      the social support received by the parents of diabetic children. The parental
      coping process was followed for a 4-week period after the diagnosis of diabetes.
      The parents of two girls, whose diabetes was diagnosed in early childhood, served
      as study subjects. Data were collected by interviewing and observing the parents
      over four separate periods. The data were analyzed by the time series and content
      analysis methods. Six phases of parental coping were identified: disbelief, lack
      of information and guilt, learning to care, normalization, uncertainty and
      reorganization. In the different phases of parental coping, the parents'
      experience of stress, coping strategies and sense of control varied. In the phase
      of disbelief, the parents tried to reject the child's diabetes by questioning the
      diagnosis. The initial information given to the parents regarding their child's
      diabetes proved to be important for parental coping. In the phase of lack of
      information and guilt, the parents sought reasons for their child's diabetes and
      felt guilty about it. As coping responses, the parents sought support from each
      other and from people who had experienced the same. In the learning to care
      phase, they recognized the demands caused by diabetes and took responsibility for
      the child's care. The parents appreciated supervision based on their problems. In
      the normalization phase, the parents prepared to return home with the diabetic
      child. Getting back to normal life was one of the most effective parental coping
      responses. In the uncertainty phase, the care to be given to the diabetic child
      changed the daily routines of the family. In the reorganization phase, the
      parents adapted to the diagnosis of diabetes and to the care of their diabetic
      child. The parents felt that the life of the family normalized and was able to be
      controlled.

PMID- 10894654
TI  - Supportive care for women with breast cancer: Australian nurses' perspective.
AB  - A research project was undertaken to describe how the support needs of women who
      have had treatment for breast cancer were being met in New South Wales,
      Australia. Data were collected from both the women and the nurses who cared for
      them. The findings from the first part of the study examined the nurses'
      perceptions of the women's needs and how they as health professionals, fulfilled
      these needs. Analysis was both qualitative and quantitative. Seventy-eight nurses
      responded to a questionnaire and 15 were interviewed. The findings indicated that
      the nurses perceived information on disease process and physical aspects of the
      disease as essential to supporting the women with breast cancer. While they saw
      providing emotional support to the women as important the nurses themselves often
      lacked the time and skills to provide it.

PMID- 10894655
TI  - Towards an international theory of nursing.
AB  - During the latter half of the 20th century, the development of numerous nursing
      theories has enriched nursing scholarship and education worldwide, a movement
      initially led by North American scholars. Recently, nurses outside of North
      America have begun to reformulate these theories in order to make them relevant
      in other contexts. This study summarizes those movements in developing an
      international theory of nursing and suggests future directions for such a theory.

PMID- 10894656
TI  - The meaning of public health nursing: creating 24 hour care in a community in
      Japan.
AB  - This case study describes the strategies and activities of public health nurses
      to increase the availability of services in a municipality of 36,000 and to
      transform community attitudes so that those needing services would feel free to
      use them. Strategies and activities are seen in the context of Japan, Minakuchi
      Town and the leadership of the chief public health nurse. Practicing in
      partnership with members of the community, strategies of public health nurses
      include technical activities (conducting needs assessment and framing program
      alternatives) and information sharing and health education (e.g. 75 meetings
      organized with health promoters for residents in the districts of the town). On
      the basis of the results of Minakuchi Town, viewed as an example of expert public
      health nursing practice, a general model for public health nursing practice is
      presented.

PMID- 10894657
TI  - Following the forsaken: a procedural description of a problem-based learning
      program in a school of nursing studies.
AB  - This paper reports the findings of one stage in an ongoing project to evaluate,
      from the students' perspectives, a student-centered problem-based learning (PBL)
      program in a School of Nursing Studies. We begin by making a comparison between
      teacher-centered education and religious devotion, and liken PBL to a
      congregation without a priest. A topographical account of the setting follows,
      describing the typical activities and events that characterize the program.
      Throughout the course of this account, a number of issues arise: the role of the
      facilitator, group dynamics, mutual responsibility and motivation for learning.
      These are touched on briefly, but we do not attempt to make a substantive
      theoretical contribution. Despite the widespread popularity of PBL in nursing
      schools, there have been few empirical studies conducted and, consequently, the
      adoption of PBL in nursing has been dependent upon the research of the very
      different discipline of medicine and medical education.

PMID- 10894658
TI  - Heart rate variability of preterm neonates quantified by energy entropy.
AB  - Identifying variables predictive of neurobehavioural sequelae is a key objective
      in the study of high-risk neonates. Examination of heart rate variability (HRV)
      characteristics may be a finer discriminator of the neonate's response to
      physiologic stressors than the mean heart rate. The energy entropy of the heart
      beat tachogram, computed in four different domains, was used to quantify the HRV
      in 13 preterm neonates. The entropies of energies were computed from 1024
      interbeat time intervals obtained once per week from 26 to 35 weeks
      postconceptional age (PCA). The energy entropy computed in three of the domains,
      like the standard deviation of intervals, distinguished between the 10 neonates
      that were measured at 35 weeks PCA with 100% specificity and 67% sensitivity, but
      did not distinguish between healthy and unhealthy neonates at earlier ages. The
      findings suggest that energy entropy may be a discerning measure of physiologic
      stress in the preterm infant, although future research is needed to refine the
      test and determine statistical significance.

PMID- 10894659
TI  - Identifying outstanding clinical nurses: the 'star' shines in oncology.
AB  - There are some oncology nurses who are special. They are 'good' nurses but they
      are more, somehow they 'shine'. They are 'stars'. Many nurses will identify the
      same nurse as a 'star' but what makes a nurse a 'star'? Twelve semistructured
      interviews were conducted in which oncology nurses were asked to describe an
      oncology nurse who stood out in terms of clinical practice. The 'star' nurse was
      easily and readily recalled and described by participants. Analysis revealed 21
      grouped themes relating to the 'star' nurse. Each theme was allocated to one of
      four headings: 'Nurses' ways of Being; Doing; Knowing; and Giving and Receiving'
      (Stiles, 1990). The 'star' nurse is professional, committed and caring; delivers
      excellent nursing care both basic and technical; is knowledgeable; has advanced
      communication skills, and establishes strong relationships with clients and
      peers. From this, it is clear that caring and psycho-social aspects of care are
      only part of the make up of the 'star' nurse, and that the complexity of the
      'star' nurse has not been highlighted in the literature.

PMID- 10894661
TI  - Expert thinking in nursing practice: implications for supporting expertise.
AB  - The complexity of the art of expert nursing practice is an elusive phenomenon,
      which is difficult to articulate in concrete terms that can be translated into
      achieving quality patient care outcomes. The present study describes the findings
      of two hermeneutic (interpretive) studies on expert thinking that captured the
      holistic practice of expert clinicians. The findings from these studies provide
      insight into how expert practice can be administratively supported. These
      findings also have strong implications for strategies to facilitate the
      development of expertise in practice. In order to provide holistic care, nurses
      must spend time with their patients so that the particularities and meaning
      inherent in each unique patient situation can be understood. The art of expert
      thinking is a temporal and ethical activity, which needs to be supported and
      cultivated in a changing health-care delivery system.

PMID- 10894660
TI  - Characteristics of circadian change in urinary frequency, bladder capacity and
      residual urine volume in elderly men with lower urinary tract symptoms.
AB  - In order to compare the daily voiding traits of elderly men with those of middle
      aged men with lower urinary tract symptoms (LUTS), urinary frequency, bladder
      capacity at normal desire to void (CNDV), residual urine volume (RUV) and
      functional bladder capacity were evaluated at home during a 24 h period using a
      non-invasive method. The results showed that in both groups, urinary frequency
      was lowest from midnight to 06.00 h. The urinary frequency was the highest from
      12.00 to 18.00 h. The CNDV in the elderly group was less than that of the middle
      aged group for 1 day. In particular, bladder capacity from 24.00 to 06.00 h
      showed the greatest difference (P < 0.05). The RUV in elderly men tended to
      accumulate more than those in middle-aged men. The findings suggest that the
      functional bladder capacity of elderly men was lower than that of middle-aged men
      in the home.

PMID- 10894662
TI  - Reflections on written comments by women on their abuse.
AB  - In a study to differentiate injuries of physical abuse from non-physical abuse,
      103 women wrote uninvited comments that were analyzed in two ways: Q-sort and
      phenomenology analyses. Q-sort identified two categories: helplessness and
      assertiveness. Comparisons with subject responses about current or previous
      violence indicated that women who wrote assertive comments were less likely to be
      in a violent relationship than women who wrote helpless comments.
      Phenomenological analysis indicated that women who were categorized as silent,
      received or subjective were in abusive relationships; some had been abused on the
      day of admission. Two women wrote comments considered subjective procedural; both
      were living with their abuser and stated that the abuse no longer occurred.
      Health-care professionals must question the appropriate goal to counsel abused
      women. Whether these two continua reflect a readiness to leave the relationship
      or result from having left, the comments by two women who say they are no longer
      being abused are more assertive and appear to show higher levels of knowing.

PMID- 10894663
TI  - The challenges facing school nurses in the management of students with cancer.

PMID- 10894664
TI  - The initial childhood diagnosis of cancer and its impact into the adolescent
      years.

PMID- 10894665
TI  - One parent shares the pain, fear ... and hope.

PMID- 10894666
TI  - Allergens, pollutants, and triggers: improving school air quality.

PMID- 10894667
TI  - A school nurse's guide to vision screening and ocular emergencies--Part 2.
      American Optometric Association.

PMID- 10894668
TI  - Children and adolescents with Long QT syndrome. Helping school nurses recognize
      signs and symptoms of this potentially deadly cardiac condition.

PMID- 10894669
TI  - Are school nurses adequately compensated?

PMID- 10894670
TI  - Children, adolescents and anger management strategies.

PMID- 10894671
TI  - New teen- and parent-friendly Web site: www.iwannaknow.org.

PMID- 10894672
TI  - Obstetric interventions among private and public patients. High rates of
      operative vaginal interventions in private patients need analysis.

PMID- 10894673
TI  - Quinolone ear drops for chronic otitis media. They are safer and more effective
      than aminoglycosides.

PMID- 10894674
TI  - Sources of Toxoplasma gondii infection in pregnancy. Until rates of congenital
      toxoplasmosis fall, control measures are essential.

PMID- 10894675
TI  - Corticosteroids in head injury. It's time for a large simple randomised trial.
      CRASH trial management group. Corticosteroid randomisation after significant head
      injury.

PMID- 10894676
TI  - Sector-wide approaches in developing countries. The aid given must make the most
      impact.

PMID- 10894677
TI  - Judge attacks South African government's response to AIDS.

PMID- 10894680
TI  - Doctor may be extradited to face criminal charges

PMID- 10894678
TI  - "War of liberation" needed to fight AIDS.

PMID- 10894682
TI  - MPs say NHS consultants should not do private work

PMID- 10894681
TI  - In brief

PMID- 10894683
TI  - No evidence of racism in GMC complaints procedures

PMID- 10894684
TI  - India introduces regulations for making traditional medicines

PMID- 10894685
TI  - In vitro fertilisation is preferable to fertility drugs

PMID- 10894686
TI  - Germany reorganises its transplant services

PMID- 10894687
TI  - Patient has coronary artery bypass surgery while awake.

PMID- 10894688
TI  - CSM attacked over delay in reducing secrecy. Committee on Safety of Medicines.

PMID- 10894689
TI  - The man from down under takes over.

PMID- 10894690
TI  - Rates for obstetric intervention among private and public patients in Australia:
      population based descriptive study.
AB  - OBJECTIVE: To compare the risk profile of women receiving public and private
      obstetric care and to compare the rates of obstetric intervention among women at
      low risk in these groups. DESIGN: Population based descriptive study. SETTING:
      New South Wales, Australia. SUBJECTS: All 171,157 women having a live baby during
      1996 and 1997. INTERVENTIONS: Epidural, augmentation or induction of labour,
      episiotomy, and births by forceps, vacuum, or caesarean section. MAIN OUTCOME
      MEASURES: Risk profile of public and private patients, intervention rates, and
      the accumulation of interventions by both patient and hospital classification
      (public or private). RESULTS: Overall, the frequency of women classified as low
      risk was similar (48%) among those choosing private obstetric care and those
      receiving standard care in a public hospital. Among low risk women, rates of
      obstetric intervention were highest in private patients in private hospitals,
      lowest in public patients, and generally intermediate for private patients in
      public hospitals. Among primiparas at low risk, 34% of private patients in
      private hospitals had a forceps or vacuum delivery compared with 17% of public
      patients. For multiparas the rates were 8% and 3% respectively. Private patients
      were significantly more likely to have interventions before birth (epidural,
      induction or augmentation) but this alone did not account for the increased
      interventions at birth, particularly the high rates of instrumental births.
      CONCLUSIONS: Public patients have a lower chance of an instrumental delivery.
      Women should have equal access to quality maternity services, but information on
      the outcomes associated with the various models of care may influence their
      choices.

PMID- 10894691
TI  - Sources of toxoplasma infection in pregnant women: European multicentre case
      control study. European Research Network on Congenital Toxoplasmosis.
AB  - OBJECTIVE: To determine the odds ratio and population attributable fraction
      associated with food and environmental risk factors for acute toxoplasmosis in
      pregnancy. DESIGN: Case-control study. SETTING: Six large European cities.
      PARTICIPANTS: Pregnant women with acute infection (cases) detected by
      seroconversion or positive for anti-Toxoplasma gondii IgM were compared with
      pregnant women seronegative for toxoplasma (controls). MAIN OUTCOME MEASURES:
      Odds ratios for acute infection adjusted for confounding variables; the
      population attributable fraction for risk factors. RESULTS: Risk factors most
      strongly predictive of acute infection in pregnant women were eating undercooked
      lamb, beef, or game, contact with soil, and travel outside Europe and the United
      States and Canada. Contact with cats was not a risk factor. Between 30% and 63%
      of infections in different centres were attributed to consumption of undercooked
      or cured meat products and 6% to 17% to soil contact. CONCLUSIONS: Inadequately
      cooked or cured meat is the main risk factor for infection with toxoplasma in all
      centres. Preventive strategies should aim to reduce prevalence of infection in
      meat, improve labelling of meat according to farming and processing methods, and
      improve the quality and consistency of health information given to pregnant
      women.

PMID- 10894692
TI  - Extent of underdiagnosis of familial hypercholesterolaemia in routine practice:
      prospective registry study.

PMID- 10894693
TI  - Risk among gastroenterologists of acquiring Helicobacter pylori infection: case
      control study.

PMID- 10894694
TI  - Impact of NHS direct on demand for immediate care: observational study.
AB  - OBJECTIVES: To quantify the impact of NHS Direct on the use of accident and
      emergency, ambulance, and general practitioner cooperative services. DESIGN:
      Observational study of trends in use of NHS Direct and other immediate care
      services over 24 months spanning introduction of NHS Direct. SETTING: Three areas
      in England in first wave of introduction of NHS Direct, and six nearby general
      practitioner cooperatives as controls. SUBJECTS: All contacts with these
      immediate care services. MAIN OUTCOME MEASURES: Changes in trends in use after
      introduction of NHS Direct. RESULTS: NHS Direct received about 68 500 calls from
      a population of 1.3 million in its first year of operation, of which 72% were out
      of hours and 22% about a child aged under 5 years. Changes in trends in use of
      accident and emergency departments and ambulance services after introduction of
      NHS Direct were small and non-significant. Changes in trends in use of general
      practitioner cooperatives were also small but significant, from an increase of
      2.0% a month before introduction of NHS Direct to -0.8% afterwards (relative
      change -2. 9% (95% confidence interval -4.2% to -1.5%)). This reduction in trend
      was significant both for calls handled by telephone advice alone and for those
      resulting in direct contact with a doctor. In contrast, the six control
      cooperatives showed no evidence of change in trend; an increase of 0.8% a month
      before NHS Direct and 0.9% after (relative change 0.1% (-0.9% to 1.1%)).
      CONCLUSION: In its first year NHS Direct did not reduce the pressure on NHS
      immediate care services, although it may have restrained increasing demand on one
      important part-general practitioners' out of hours services.

PMID- 10894696
TI  - Lesson of the week. Unrecognised accidental overdose with diltiazem.

PMID- 10894697
TI  - ABC of oral health. Mouth ulcers and other causes of orofacial soreness and pain.

PMID- 10894695
TI  - Extracts from "Clinical Evidence". Malaria: prevention in travellers.
AB  - DEFINITION: Malaria is caused by a protozoan infection of red blood cells with
      one of four species of the genus plasmodium: P falciparum, P vivax, P ovale, or P
      malariae. Clinically, malaria may present in different ways, but it is usually
      characterised by fever (which may be swinging), tachycardia, rigors, and
      sweating. Anaemia, hepatosplenomegaly, cerebral involvement, renal failure, and
      shock may occur. INCIDENCE/PREVALENCE: Each year there are 300-500 million
      clinical cases of malaria. About 40% of the world's population is at risk of
      acquiring the disease. Each year 25-30 million people from non-tropical countries
      visit areas in which malaria is endemic, of whom between 10,000 and 30,000
      contract malaria. AETIOLOGY/RISK FACTORS: Malaria is mainly a rural disease,
      requiring standing water nearby. It is transmitted by bites from infected female
      anopheline mosquitoes, mainly at dusk and during the night. In cities, mosquito
      bites are usually from female culicene mosquitoes, which are not vectors of
      malaria. Malaria is resurgent in most tropical countries and the risk to
      travellers is increasing. PROGNOSIS: Ninety per cent of travellers who contract
      malaria do not become ill until after they return home. "Imported malaria" is
      easily treated if diagnosed promptly, and it follows a serious course in only
      about 12% of people. The most severe form of the disease is cerebral malaria,
      with a case fatality rate in adult travellers of 2-6%, mainly because of delays
      in diagnosis. AIMS: To reduce the risk of infection; to prevent illness and
      death. OUTCOMES: Rates of malarial illness and death, and adverse effects of
      treatment. Proxy measures include number of mosquito bites and number of
      mosquitoes in indoor areas. We found limited evidence linking number of mosquito
      bites and risk of malaria. METHODS: Clinical Evidence search and appraisal in
      November 1999. We reviewed all identified systematic reviews and randomised
      controlled trials (RCTs).

PMID- 10894698
TI  - The internet and a "small miracle"

PMID- 10894699
TI  - Deaths among humanitarian workers.

PMID- 10894700
TI  - Conflict and health: The health costs of war: can they be measured? Lessons from
      El Salvador.

PMID- 10894701
TI  - Words unsaid

PMID- 10894702
TI  - Obituaries

PMID- 10894703
TI  - Parliament approves changes to GMC

PMID- 10894704
TI  - 50 years of ideas in health care buildings

PMID- 10894705
TI  - Respiratory support in intensive care

PMID- 10894706
TI  - 28 days

PMID- 10894707
TI  - Magda segal: picturing women's health

PMID- 10894708
TI  - On earth as it is in hell

PMID- 10894709
TI  - Obstetrics

PMID- 10894710
TI  - Learning the hard way

PMID- 10894712
TI  - Instrumental births are more common among women receiving private obstetric care

PMID- 10894711
TI  - Quaint or what?

PMID- 10894713
TI  - Undercooked or cured meat is main risk factor for toxoplasmosis in pregnancy

PMID- 10894714
TI  - Familial hypercholesterolaemia is greatly underdiagnosed

PMID- 10894715
TI  - Gastroenterologists do have a higher risk of acquiring H pylori infection

PMID- 10894716
TI  - NHS direct has had little impact on demand for immediate health care

PMID- 10894717
TI  - Humanitarian aid workers increasingly risk death from intentional violence

PMID- 10894719
TI  - Self-assembly of the Agrobacterium tumefaciens VirB11 traffic ATPase.
AB  - The Agrobacterium tumefaciens VirB11 ATPase is a component of a type IV
      transporter dedicated to T-DNA delivery to plant cells. In this study, we tested
      a prediction from genetic findings that VirB11 self-associates in vivo. A
      chimeric protein composed of VirB11 fused to the DNA binding domain of lambda cI
      repressor protein formed dimers, as shown by immunity of Escherichia coli to
      lambda superinfection. An allele encoding VirB11 fused at its C terminus to the
      green fluorescent protein (GFP) exerted strong negative dominance when
      synthesized in wild-type A. tumefaciens cells. Dominance was suppressed by
      overproduction of native VirB11, suggestive of titrating or competitive
      interactions between VirB11 and VirB11::GFP. In support of the titration model, a
      complex of native VirB11 and VirB11::GFP was recovered by precipitation with anti
      GFP antibodies from detergent-solubilized A. tumefaciens cell extracts. VirB11
      was shown by cI repressor fusion and immunoprecipitation assays to interact with
      VirB11 derivatives encoded by (i) 11 dominant negative alleles, (ii) recessive
      alleles bearing codon substitutions or deletions in the Walker A nucleotide
      binding motif, and (iii) alleles corresponding to the 5' and 3' halves of virB11.
      Further immunoprecipitation studies showed a hybrid protein composed of the N
      terminal half of VirB11 fused to GFP interacted with mutant proteins exerting
      dominant effects and with a recessive Walker A deletion mutant (Delta GKT174
      176). By contrast, a hybrid protein composed of the C-terminal half fused to GFP
      interacted with mutants exerting dominant effects but not the Walker A mutant
      protein. Together, these studies establish that VirB11 assembles as homomultimers
      in vivo via domains residing in each half of the protein. Furthermore, ATP
      binding appears to be critical for C-terminal interactions required for assembly
      of productive homomultimers.

PMID- 10894718
TI  - The bacterial enhancer-dependent sigma(54) (sigma(N)) transcription factor.

PMID- 10894720
TI  - Two active forms of UDP-N-acetylglucosamine enolpyruvyl transferase in gram
      positive bacteria.
AB  - Gene sequences encoding the enzymes UDP-N-acetylglucosamine enolpyruvyl
      transferase (MurA) from many bacterial sources were analyzed. It was shown that
      whereas gram-negative bacteria have only one murA gene, gram-positive bacteria
      have two distinct genes encoding these enzymes which have possibly arisen from
      gene duplication. The two murA genes of the gram-positive organism Streptococcus
      pneumoniae were studied further. Each of the murA genes was individually
      inactivated by allelic replacement. In each case, the organism was viable despite
      losing one of its murA genes. However, when attempts were made to construct a
      double-deletion strain, no mutants were obtained. This indicates that both genes
      encode active enzymes that can substitute for each other, but that the presence
      of a MurA function is essential to the organism. The two genes were further
      cloned and overexpressed, and the enzymes they encode were purified. Both enzymes
      catalyzed the transfer of enolpyruvate from phosphoenolpyruvate to UDP-N
      acetylglucosamine, confirming they are both active UDP-N-acetylglucosamine
      enolpyruvyl transferases. The catalytic parameters of the two enzymes were
      similar, and they were both inhibited by the antibiotic fosfomycin.

PMID- 10894721
TI  - A gene cluster for the mevalonate pathway from Streptomyces sp. Strain CL190.
AB  - A biosynthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1. 1.1.34),
      the rate-limiting enzyme of the mevalonate pathway for isopentenyl diphosphate
      biosynthesis, had previously been purified from Streptomyces sp. strain CL190 and
      its corresponding gene (hmgr) had been cloned (S. Takahashi, T. Kuzuyama, and H.
      Seto, J. Bacteriol. 181:1256-1263, 1999). Sequence analysis of the flanking
      regions of the hmgr gene revealed five new open reading frames, orfA to -E, which
      showed similarity to those encoding eucaryotic and archaebacterial enzymes for
      the mevalonate pathway. Feeding experiments with [1-(13)C]acetate demonstrated
      that Escherichia coli JM109 harboring the hmgr gene and these open reading frames
      used the mevalonate pathway under induction with isopropyl beta-D
      thiogalactopyranoside. This transformant could grow in the presence of
      fosmidomycin, a potent and specific inhibitor of the nonmevalonate pathway,
      indicating that the mevalonate pathway, intrinsically absent in E. coli, is
      operating in the E. coli transformant. The hmgr gene and orfABCDE are thus
      unambiguously shown to be responsible for the mevalonate pathway and to form a
      gene cluster in the genome of Streptomyces sp. strain CL190.

PMID- 10894722
TI  - Global adaptations resulting from high population densities in Escherichia coli
      cultures.
AB  - The scope of population density effects was investigated in steady-state
      continuous cultures of Escherichia coli in the absence of complications caused by
      transient environmental conditions and growth rates. Four distinct bacterial
      properties reflecting major regulatory and physiological circuits were analyzed.
      The metabolome profile of bacteria growing at high density contained major
      differences from low-density cultures. The 10-fold-elevated level of trehalose at
      higher densities pointed to the increased role of the RpoS sigma factor, which
      controls trehalose synthesis genes as well as the general stress response. There
      was an eightfold difference in RpoS levels between bacteria grown at 10(8) and at
      10(9) cells/ml. In contrast, the cellular content of the DNA binding protein H
      NS, controlling many genes in concert with RpoS, was decreased by high density.
      Since H-NS and RpoS also influence porin gene expression, the influence of
      population density on the intricate regulation of outer membrane composition was
      also investigated. High culture densities were found to strongly repress ompF
      porin transcription, with a sharp threshold at a density of 4.4 x 10(8) cells/ml,
      while increasing the proportion of OmpC in the outer membrane. The density
      dependent regulation of ompF was maintained in rpoS or hns mutants and so was
      independent of these regulators. The consistently dramatic changes indicate that
      actively growing, high-density cultures are at least as differentiated from low
      density cultures as are exponential- from stationary-phase bacteria.

PMID- 10894723
TI  - Characterization of a second tfd gene cluster for chlorophenol and chlorocatechol
      metabolism on plasmid pJP4 in Ralstonia eutropha JMP134(pJP4).
AB  - Within the 5.9-kb DNA region between the tfdR and tfdK genes on the 2,4
      dichlorophenoxyacetic acid (2,4-D) catabolic plasmid pJP4 from Ralstonia eutropha
      JMP134, we identified five open reading frames (ORFs) with significant homology
      to the genes for chlorocatechol and chlorophenol metabolism (tfdCDEF and tfdB)
      already present elsewhere on pJP4. The five ORFs were organized and assigned as
      follows: tfdD(II)C(II)E(II)F(II) and tfdB(II) (in short, the tfd(II) cluster), by
      analogy to tfdCDEF and tfdB (the tfd(I) cluster). Primer extension analysis of
      mRNA isolated from 2,4-D-grown R. eutropha JMP134 identified a single
      transcription start site in front of the first gene of the cluster, tfdD(II),
      suggesting an operon-like organization for the tfd(II) genes. By expressing each
      ORF in Escherichia coli, we confirmed that tfdD(II) coded for a chloromuconate
      cycloisomerase, tfdC(II) coded for a chlorocatechol 1, 2-dioxygenase, tfdE(II)
      coded for a dienelactone hydrolase, tfdF(II) coded for a maleylacetate reductase,
      and tfdB(II) coded for a chlorophenol hydroxylase. Dot blot hybridizations of
      mRNA isolated from R. eutropha JMP134 showed that both tfd(I) and tfd(II) genes
      are transcribed upon induction with 2,4-D. Thus, the functions encoded by the
      tfd(II) genes seem to be redundant with respect to those of the tfd(I) cluster.
      One reason why the tfd(II) genes do not disappear from plasmid pJP4 might be the
      necessity for keeping the regulatory genes for the 2,4-D pathway expression tfdR
      and tfdS.

PMID- 10894724
TI  - Regulation of acetyl coenzyme A synthetase in Escherichia coli.
AB  - Cells of Escherichia coli growing on sugars that result in catabolite repression
      or amino acids that feed into glycolysis undergo a metabolic switch associated
      with the production and utilization of acetate. As they divide exponentially,
      these cells excrete acetate via the phosphotransacetylase-acetate kinase pathway.
      As they begin the transition to stationary phase, they instead resorb acetate,
      activate it to acetyl coenzyme A (acetyl-CoA) by means of the enzyme acetyl-CoA
      synthetase (Acs) and utilize it to generate energy and biosynthetic components
      via the tricarboxylic acid cycle and the glyoxylate shunt, respectively. Here, we
      present evidence that this switch occurs primarily through the induction of acs
      and that the timing and magnitude of this induction depend, in part, on the
      direct action of the carbon regulator cyclic AMP receptor protein (CRP) and the
      oxygen regulator FNR. It also depends, probably indirectly, upon the glyoxylate
      shunt repressor IclR, its activator FadR, and many enzymes involved in acetate
      metabolism. On the basis of these results, we propose that cells induce acs, and
      thus their ability to assimilate acetate, in response to rising cyclic AMP
      levels, falling oxygen partial pressure, and the flux of carbon through acetate
      associated pathways.

PMID- 10894725
TI  - Coactivation of the RpoS-dependent proP P2 promoter by fis and cyclic AMP
      receptor protein.
AB  - The Escherichia coli proP P2 promoter, which directs the expression of an
      integral membrane transporter of proline, glycine betaine, and other
      osmoprotecting compounds, is induced upon entry into stationary phase to protect
      cells from osmotic shock. Transcription from the P2 promoter is completely
      dependent on RpoS (sigma(38)) and Fis. Fis activates transcription by binding to
      a site centered at -41, which overlaps the promoter, where it makes a specific
      contact with the C-terminal domain of the alpha subunit of RNA polymerase (alpha
      CTD). We show here that Fis and cyclic AMP (cAMP) receptor protein (CRP)-cAMP
      collaborate to activate transcription synergistically in vitro. Coactivation both
      in vivo and in vitro is dependent on CRP binding to a site centered at -121.5,
      but CRP without Fis provides little activation. The contribution by CRP requires
      the correct helical phasing of the CRP site and a functional activation region 1
      on CRP. We provide evidence that coactivation is achieved by Fis and CRP
      independently contacting each of the two alpha-CTDs. Efficient transcription in
      vitro requires that both activators must be preincubated with the DNA prior to
      addition of RNA polymerase.

PMID- 10894727
TI  - Reconstitution and partial characterization of phospholipid flippase activity
      from detergent extracts of the Bacillus subtilis cell membrane.
AB  - In bacteria, phospholipids are synthesized on the inner leaflet of the
      cytoplasmic membrane and must translocate to the outer leaflet to propagate a
      bilayer. Transbilayer movement of phospholipids has been shown to be fast and
      independent of metabolic energy, and it is predicted to be facilitated by
      membrane proteins (flippases) since transport across protein-free membranes is
      negligible. However, it remains unclear as to whether proteins are required at
      all and, if so, whether specific proteins are needed. To determine whether
      bacteria contain specific proteins capable of translocating phospholipids across
      the cytoplasmic membrane, we reconstituted a detergent extract of Bacillus
      subtilis into proteoliposomes and measured import of a water-soluble phospholipid
      analog. We found that the proteoliposomes were capable of transporting the analog
      and that transport was inhibited by protease treatment. Active proteoliposome
      populations were also able to translocate a long-chain phospholipid, as judged by
      a phospholipase A(2)-based assay. Protein-free liposomes were inactive. We show
      that manipulation of the reconstitution mixture by prior chromatographic
      fractionation of the detergent extract, or by varying the protein/phospholipid
      ratio, results in populations of vesicles with different specific activities.
      Glycerol gradient analysis showed that the majority of the transport activity
      sedimented at approximately 4S, correlating with the presence of specific
      proteins. Recovery of activity in other gradient fractions was low despite the
      presence of a complex mixture of proteins. We conclude that bacteria contain
      specific proteins capable of facilitating transbilayer translocation of
      phospholipids. The reconstitution methodology that we describe provides the basis
      for purifying a facilitator of transbilayer phospholipid translocation in
      bacteria.

PMID- 10894726
TI  - HARO7 encodes chorismate mutase of the methylotrophic yeast Hansenula polymorpha
      and is derepressed upon methanol utilization.
AB  - The HARO7 gene of the methylotrophic, thermotolerant yeast Hansenula polymorpha
      was cloned by functional complementation. HARO7 encodes a monofunctional 280
      amino-acid protein with chorismate mutase (EC 5.4. 99.5) activity that catalyzes
      the conversion of chorismate to prephenate, a key step in the biosynthesis of
      aromatic amino acids. The HARO7 gene product shows strong similarities to primary
      sequences of known eukaryotic chorismate mutase enzymes. After homologous
      overexpression and purification of the 32-kDa protein, its kinetic parameters
      (k(cat) = 319.1 s(-1), n(H) = 1.56, [S](0.5) = 16.7 mM) as well as its allosteric
      regulatory properties were determined. Tryptophan acts as heterotropic positive
      effector; tyrosine is a negative-acting, heterotropic feedback inhibitor of
      enzyme activity. The influence of temperature on catalytic turnover and the
      thermal stability of the enzyme were determined and compared to features of the
      chorismate mutase enzyme of Saccharomyces cerevisiae. Using the Cre-loxP
      recombination system, we constructed mutant strains carrying a disrupted HARO7
      gene that showed tyrosine auxotrophy and severe growth defects. The amount of the
      0.9-kb HARO7 mRNA is independent of amino acid starvation conditions but
      increases twofold in the presence of methanol as the sole carbon source, implying
      a catabolite repression system acting on HARO7 expression.

PMID- 10894728
TI  - Role of FliJ in flagellar protein export in Salmonella.
AB  - We isolated and characterized spontaneous mutants with defects in the 147-amino
      acid Salmonella protein FliJ, which is a cytoplasmic component of the type III
      flagellar export apparatus. These mutants, including ones with null mutations,
      have the ability to form swarms on motility agar plates after prolonged
      incubation at 30 degrees C; i.e., they display a leaky motile phenotype. One
      mutant, SJW277, which formed significantly bigger swarms than the others, encoded
      only the N-terminal 73 amino acids of FliJ, one-half of the protein. At 30
      degrees C, overproduction of this mutant protein improved, to wild-type levels,
      both motility and the ability to export both rod/hook-type (FlgD; hook capping
      protein) and filament-type (FliC; flagellin) substrates. At 42 degrees C,
      however, export was inhibited, indicating that the mutant FliJ protein was
      temperature sensitive. Taking advantage of this, we performed temperature upshift
      experiments, which demonstrated that FliJ is directly required for the export of
      FliC. Co-overproduction of FliJ and either of two export substrates, FliE or
      FlgG, hindered their aggregation in the cytoplasm. We conclude that FliJ is a
      general component of the flagellar export apparatus and has a chaperone-like
      activity for both rod/hook-type and filament-type substrates.

PMID- 10894729
TI  - New substrates for the dicarboxylate transport system of Sinorhizobium meliloti.
AB  - The dicarboxylate transport (Dct) system of Sinorhizobium meliloti, which is
      essential for a functional nitrogen-fixing symbiosis, has been thought to
      transport only dicarboxylic acids. We show here that the permease component of
      the Dct system, DctA, can transport orotate, a monocarboxylic acid, with an
      apparent K(m) of 1.7 mM and a V(max) of 163 nmol min(-1) per mg of protein in
      induced cells. DctA was not induced by the presence of orotate. The transport of
      orotate was inhibited by several compounds, including succinamic acid and
      succinamide, which are not dicarboxylic acids. The dicarboxylic acid maleate (cis
      butenedioic acid) was not an inhibitor of orotate transport, which suggests that
      it was not recognized by DctA. However, maleate was an excellent inducer of DctA
      expression. Our evaluation of 17 compounds as inducers and inhibitors of
      transport suggests that substrates recognized by S. meliloti DctA must have
      appropriately spaced carbonyl groups and an extended conformation, while good
      inducers are more likely to have a curved conformation.

PMID- 10894730
TI  - Analysis of the cellular localization of Bdr paralogs in Borrelia burgdorferi, a
      causative agent of lyme disease: evidence for functional diversity.
AB  - The bdr (Borrelia direct repeat) gene family of the genus Borrelia encodes a
      polymorphic group of proteins that carry a central repeat motif region containing
      putative phosphorylation sites and a hydrophobic carboxyl-terminal domain. It has
      been postulated that the Bdr proteins may anchor to the inner membrane via the C
      terminal domain. In this study, we used cellular fractionation methodologies,
      salt and detergent treatments, and immunoblot analyses to assess the association
      of the Bdr proteins with the cellular infrastructure in both Borrelia burgdorferi
      (a Lyme disease spirochete) and B. turicatae (a relapsing fever spirochete).
      Triton X-114 extraction and partitioning experiments demonstrated that most Bdr
      paralogs are associated with the inner membrane-peptidoglycan complex. Analyses
      of cells treated with the highly chaotropic bile salt detergent deoxycholic acid
      demonstrated that some Bdr paralogs may also interact with the peptidoglycan, as
      evidenced by their tight association with the insoluble cellular matrix. In
      addition, immunoprecipitation (IP) experiments revealed an enhanced IP of all Bdr
      paralogs when the cell lysates were boiled prior to addition of the precipitating
      antibody. Furthermore, some Bdr paralogs were accessible to antibody in the IP
      experiments only in the boiled cell lysates. These observations suggest that
      different Bdr paralogs may carry out different structural-functional roles.
      Demonstration of the inner membrane localization of the Bdr proteins and of the
      differences in nature of the interaction of individual Bdr paralogs with the cell
      infrastructure is an important step toward defining the functional role of this
      unique protein family in the genus Borrelia.

PMID- 10894731
TI  - Identification of an alternative nucleoside triphosphate: 5'
      deoxyadenosylcobinamide phosphate nucleotidyltransferase in Methanobacterium
      thermoautotrophicum delta H.
AB  - Computer analysis of the archaeal genome databases failed to identify orthologues
      of all of the bacterial cobamide biosynthetic enzymes. Of particular interest was
      the lack of an orthologue of the bifunctional nucleoside triphosphate (NTP):5'
      deoxyadenosylcobinamide kinase/GTP:adenosylcobinamide-phosphate
      guanylyltransferase enzyme (CobU in Salmonella enterica). This paper reports the
      identification of an archaeal gene encoding a new nucleotidyltransferase, which
      is proposed to be the nonorthologous replacement of the S. enterica cobU gene.
      The gene encoding this nucleotidyltransferase was identified using comparative
      genome analysis of the sequenced archaeal genomes. Orthologues of the gene
      encoding this activity are limited at present to members of the domain Archaea.
      The corresponding ORF open reading frame from Methanobacterium
      thermoautotrophicum Delta H (MTH1152; referred to as cobY) was amplified and
      cloned, and the CobY protein was expressed and purified from Escherichia coli as
      a hexahistidine-tagged fusion protein. This enzyme had GTP:adenosylcobinamide
      phosphate guanylyltransferase activity but did not have the NTP:AdoCbi kinase
      activity associated with the CobU enzyme of S. enterica. NTP:adenosylcobinamide
      kinase activity was not detected in M. thermoautotrophicum Delta H cell extract,
      suggesting that this organism may not have this activity. The cobY gene
      complemented a cobU mutant of S. enterica grown under anaerobic conditions where
      growth of the cell depended on de novo adenosylcobalamin biosynthesis. cobY,
      however, failed to restore adenosylcobalamin biosynthesis in cobU mutants grown
      under aerobic conditions where de novo synthesis of this coenzyme was blocked,
      and growth of the cell depended on the assimilation of exogenous cobinamide.
      These data strongly support the proposal that the relevant cobinamide
      intermediates during de novo adenosylcobalamin biosynthesis are
      adenosylcobinamide-phosphate and adenosylcobinamide-GDP, not adenosylcobinamide.
      Therefore, NTP:adenosylcobinamide kinase activity is not required for de novo
      cobamide biosynthesis.

PMID- 10894733
TI  - Simultaneous identification of two cyclohexanone oxidation genes from an
      environmental Brevibacterium isolate using mRNA differential display.
AB  - The technique of mRNA differential display was used to identify simultaneously
      two metabolic genes involved in the degradation of cyclohexanone in a new
      halotolerant Brevibacterium environmental isolate. In a strategy based only on
      the knowledge that cyclohexanone oxidation was inducible in this strain, the mRNA
      population of cells exposed to cyclohexanone was compared to that of control
      cells using reverse transcription-PCR reactions primed with a collection of 81
      arbitrary oligonucleotides. Three DNA fragments encoding segments of flavin
      monooxygenases were isolated with this technique, leading to the identification
      of the genes of two distinct cyclohexanone monooxygenases, the enzymes
      responsible for the oxidation of cyclohexanone. Each monooxygenase was expressed
      in Escherichia coli and characterized. This work validates the application of
      mRNA differential display for the discovery of new microbial metabolic genes.

PMID- 10894732
TI  - Requirements for conversion of the Na(+)-driven flagellar motor of Vibrio
      cholerae to the H(+)-driven motor of Escherichia coli.
AB  - Bacterial flagella are powered by a motor that converts a transmembrane
      electrochemical potential of either H(+) or Na(+) into mechanical work. In
      Escherichia coli, the MotA and MotB proteins form the stator and function in
      proton translocation, whereas the FliG protein is located on the rotor and is
      involved in flagellar assembly and torque generation. The sodium-driven polar
      flagella of Vibrio species contain homologs of MotA and MotB, called PomA and
      PomB, and also contain two other membrane proteins called MotX and MotY, which
      are essential for motor rotation and that might also function in ion conduction.
      Deletions in pomA, pomB, motX, or motY in Vibrio cholerae resulted in a nonmotile
      phenotype, whereas deletion of fliG gave a nonflagellate phenotype. fliG genes on
      plasmids complemented fliG-null strains of the parent species but not fliG-null
      strains of the other species. FliG-null strains were complemented by chimeric
      FliG proteins in which the C-terminal domain came from the other species,
      however, implying that the C-terminal part of FliG can function in conjunction
      with the ion-translocating components of either species. A V. cholerae strain
      deleted of pomA, pomB, motX, and motY became weakly motile when the E. coli motA
      and motB genes were introduced on a plasmid. Like E. coli, but unlike wild-type
      V. cholerae, motility of some V. cholerae strains containing the hybrid motor was
      inhibited by the protonophore carbonyl cyanide m-chlorophenylhydrazone under
      neutral as well as alkaline conditions but not by the sodium motor-specific
      inhibitor phenamil. We conclude that the E. coli proton motor components MotA and
      MotB can function in place of the motor proteins of V. cholerae and that the
      hybrid motors are driven by the proton motive force.

PMID- 10894734
TI  - Saccharomyces cerevisiae sigma 1278b has novel genes of the N-acetyltransferase
      gene superfamily required for L-proline analogue resistance.
AB  - We discovered on the chromosome of Saccharomyces cerevisiae Sigma 1278b novel
      genes involved in L-proline analogue L-azetidine-2-carboxylic acid resistance
      which are not present in the standard laboratory strains. The 5.4 kb-DNA fragment
      was cloned from the genomic library of the L-azetidine-2-carboxylic acid
      resistant mutant derived from a cross between S. cerevisiae strains S288C and
      Sigma 1278b. The nucleotide sequence of a 4.5-kb segment exhibited no identity
      with the sequence in the genome project involving strain S288C. Deletion analysis
      indicated that one open reading frame encoding a predicted protein of 229 amino
      acids is indispensable for L-azetidine-2-carboxylic acid resistance. The protein
      sequence was found to be a member of the N-acetyltransferase superfamily. Genomic
      Southern analysis and gene disruption showed that two copies of the novel gene
      with one amino acid change at position 85 required for L-azetidine-2-carboxylic
      acid resistance were present on chromosomes X and XIV of Sigma 1278b background
      strains. When this novel MPR1 or MPR2 gene (sigma 1278b gene for L-proline
      analogue resistance) was introduced into the other S. cerevisiae strains, all of
      the recombinants were resistant to L-azetidine-2-carboxylic acid, indicating that
      both MPR1 and MPR2 are expressed and have a global function in S. cerevisiae.

PMID- 10894735
TI  - Transcriptional analysis of major heat shock genes of Helicobacter pylori.
AB  - The transcriptional organization and heat inducibility of the major heat shock
      genes hrcA, dnaK, dnaJ, groEL, and htpG were analyzed on the transcriptional
      level in Helicobacter pylori strain 69A. The strongly heat-induced dnaK operon
      was found to be tricistronic, consisting of the genes hrcA, grpE, and dnaK. The
      dnaJ gene specified one monocistronic mRNA which was also heat inducible. The
      genes groES and groEL were transcribed as one strongly heat-inducible bicistronic
      mRNA which exhibited exactly the same induction kinetic as the dnaK operon.
      Surprisingly, transcription of the monocistronic htpG gene was switched off after
      heat shock. The data presented are discussed with regard to the different
      mechanisms regulating expression of heat shock genes in H. pylori

PMID- 10894736
TI  - Cross-linked complex between oligomeric periplasmic lipoprotein AcrA and the
      inner-membrane-associated multidrug efflux pump AcrB from Escherichia coli.
AB  - In Escherichia coli, the intrinsic levels of resistance to multiple antimicrobial
      agents are produced through expression of the three-component multidrug efflux
      system AcrAB-TolC. AcrB is a proton-motive-force-dependent transporter located in
      the inner membrane, and AcrA and TolC are accessory proteins located in the
      periplasm and the outer membrane, respectively. In this study, these three
      proteins were expressed separately, and the interactions between them were
      analyzed by chemical cross-linking in intact cells. We show that AcrA protein
      forms oligomers, most probably trimers. In this oligomeric form, AcrA interacts
      specifically with AcrB transporter independently of substrate and TolC.

PMID- 10894737
TI  - A redox-responsive regulator of photosynthesis gene expression in the
      cyanobacterium Synechocystis sp. Strain PCC 6803.
AB  - We have identified genes in the unicellular cyanobacterium Synechocystis sp.
      strain PCC 6803 that are involved with redox control of photosynthesis and
      pigment-related genes. The genes, rppA (sll0797) and rppB (sll0798), represent a
      two-component regulatory system that controls the synthesis of photosystem II
      (PSII) and PSI genes, in addition to photopigment-related genes. rppA (regulator
      of photosynthesis- and photopigment-related gene expression) and rppB exhibit
      strong sequence similarity to prokaryotic response regulators and histidine
      kinases, respectively. In the wild type, the steady-state mRNA levels of PSII
      reaction center genes increased when the plastoquinone (PQ) pool was oxidized and
      decreased when the PQ pool was reduced, whereas transcription of the PSI reaction
      center genes was affected in an opposite fashion. Such results suggested that the
      redox poise of the PQ pool is critical for regulation of the photosystem reaction
      center genes. In Delta rppA, an insertion mutation of rppA, the PSII gene
      transcripts were highly up-regulated relative to the wild type under all redox
      conditions, whereas transcription of phycobilisome-related genes and PSI genes
      was decreased. The higher transcription of the psbA gene in Delta rppA was
      manifest by higher translation of the D1 protein and a concomitant increase in
      O(2) evolution. The results demonstrated that RppA is a regulator of
      photosynthesis- and photopigment-related gene expression, is involved in the
      establishment of the appropriate stoichiometry between the photosystems, and can
      sense changes in the PQ redox poise.

PMID- 10894738
TI  - A soxA gene, encoding a diheme cytochrome c, and a sox locus, essential for
      sulfur oxidation in a new sulfur lithotrophic bacterium.
AB  - A mobilizable suicide vector, pSUP5011, was used to introduce Tn5-mob in a new
      facultative sulfur lithotrophic bacterium, KCT001, to generate mutants defective
      in sulfur oxidation (Sox(-)). The Sox(-) mutants were unable to oxidize
      thiosulfate while grown mixotrophically in the presence of thiosulfate and
      succinate. The mutants were also impaired in oxidizing other reduced sulfur
      compounds and elemental sulfur as evident from the study of substrate oxidation
      by the whole cells. Sulfite oxidase activity was significantly diminished in the
      cell extracts of all the mutants. A soxA gene was identified from the transposon
      adjacent genomic DNA of a Sox(-) mutant strain. The sequence analysis revealed
      that the soxA open reading frame (ORF) is preceded by a potential ribosome
      binding site and promoter region with -10- and -35-like sequences. The deduced
      nucleotide sequence of the soxA gene was predicted to code for a protein of 286
      amino acids. It had a signal peptide of 26 N-terminal amino acids. The amino acid
      sequence showed similarity with a putative gene product of Aquifex aeolicus,
      soluble cytochrome c(551) of Chlorobium limicola, and the available partial SoxA
      sequence of Paracoccus denitrificans. The soxA-encoded product seems to be a
      diheme cytochrome c for KCT001 and A. aeolicus, but the amino acid sequence of C.
      limicola cytochrome c(551) revealed a single heme-binding region. Another
      transposon insertion mutation was mapped within the soxA ORF. Four other
      independent transposon insertion mutations were mapped in the 4.4-kb soxA
      contiguous genomic DNA region. The results thus suggest that a sox locus of
      KCT001, essential for sulfur oxidation, was affected by all these six independent
      insertion mutations.

PMID- 10894739
TI  - Metabolic instability of Escherichia coli cyclopropane fatty acid synthase is due
      to RpoH-dependent proteolysis.
AB  - Cyclopropane fatty acids (CFAs) are generally synthesized as bacterial cultures
      enter stationary phase. In Escherichia coli, the onset of CFA synthesis results
      from increased transcription of cfa, the gene encoding CFA synthase. However, the
      increased level of CFA synthase activity is transient; the activity quickly
      declines to the basal level. We report that the loss of CFA activity is due to
      proteolytic degradation dependent on expression of the heat shock regulon. CFA
      synthase degradation is unaffected by mutations in the lon, clpP, and groEL genes
      or by depletion of the intracellular ATP pools. It seems likely that CFA synthase
      is the target of an unidentified energy-independent heat shock regulon protease.
      This seems to be the first example of heat shock-dependent degradation of a
      normal biosynthetic enzyme.

PMID- 10894740
TI  - Vibrio cholerae H-NS silences virulence gene expression at multiple steps in the
      ToxR regulatory cascade.
AB  - H-NS is an abundant nucleoid-associated protein involved in the maintenance of
      chromosomal architecture in bacteria. H-NS also has a role in silencing the
      expression of a variety of environmentally regulated genes during growth under
      nonpermissive conditions. In this study we demonstrate a role for H-NS in the
      negative modulation of expression of several genes within the ToxR virulence
      regulon of Vibrio cholerae. Deletion of hns resulted in high, nearly constitutive
      levels of expression of the genes encoding cholera toxin, toxin-coregulated
      pilus, and the ToxT virulence gene regulatory protein. For the cholera toxin- and
      ToxT-encoding genes, elevated expression in an hns mutant was found to occur in
      the absence of the cognate activator proteins, suggesting that H-NS functions
      directly at these promoters to decrease gene expression. Deletion analysis of the
      region upstream of toxT suggests that an extensive region located far upstream of
      the transcriptional start site is required for complete H-NS-mediated repression
      of gene expression. These data indicate that H-NS negatively influences multiple
      levels of gene expression within the V. cholerae virulence cascade and raise the
      possibility that the transcriptional activator proteins in the ToxR regulon
      function to counteract the repressive effects of H-NS at the various promoters as
      well as to recruit RNA polymerase.

PMID- 10894741
TI  - Reduction of Cob(III)alamin to Cob(II)alamin in Salmonella enterica serovar
      typhimurium LT2.
AB  - Reduction of the cobalt ion of cobalamin from the Co(III) to the Co(I) oxidation
      state is essential for the synthesis of adenosylcobalamin, the coenzymic form of
      this cofactor. A cob(II)alamin reductase activity in Salmonella enterica serovar
      Typhimurium LT2 was isolated to homogeneity. N-terminal analysis of the
      homogeneous protein identified NAD(P)H:flavin oxidoreductase (Fre) (EC 1.6.8.1)
      as the enzyme responsible for this activity. The fre gene was cloned, and the
      overexpressed protein, with a histidine tag at its N terminus, was purified to
      homogeneity by nickel affinity chromatography. His-tagged Fre reduced flavins
      (flavin mononucleotide [FMN] and flavin adenine dinucleotide [FAD]) and
      cob(III)alamin to cob(II)alamin very efficiently. Photochemically reduced FMN
      substituted for Fre in the reduction of cob(III)alamin to cob(II)alamin,
      indicating that the observed cobalamin reduction activity was not Fre dependent
      but FMNH(2) dependent. Enzyme-independent reduction of cob(III)alamin to
      cob(II)alamin by FMNH(2) occurred at a rate too fast to be measured. The
      thermodynamically unfavorable reduction of cob(II)alamin to cob(I)alamin was
      detectable by alkylation of the cob(I)alamin nucleophile with iodoacetate.
      Detection of the product, caboxymethylcob(III)alamin, depended on the presence of
      FMNH(2) in the reaction mixture. FMNH(2) failed to substitute for potassium
      borohydride in in vitro assays for corrinoid adenosylation catalyzed by the
      ATP:co(I)rrinoid adenosyltransferase (CobA) enzyme, even under conditions where
      Fre and NADH were present in the reaction mixture to ensure that FMN was always
      reduced. These results were interpreted to mean that Fre was not responsible for
      the generation of cob(I)alamin in vivo. Consistent with this idea, a fre mutant
      displayed wild-type cobalamin biosynthetic phenotypes. It is proposed that S.
      enterica serovar Typhimurium LT2 may not have a cob(III)alamin reductase enzyme
      and that, in vivo, nonadenosylated cobalamin and other corrinoids are maintained
      as co(II)rrinoids by reduced flavin nucleotides generated by Fre and other flavin
      oxidoreductases.

PMID- 10894742
TI  - Alfalfa root nodule invasion efficiency is dependent on Sinorhizobium meliloti
      polysaccharides.
AB  - The soil bacterium Sinorhizobium meliloti is capable of entering into a nitrogen
      fixing symbiosis with Medicago sativa (alfalfa). Particular low-molecular-weight
      forms of certain polysaccharides produced by S. meliloti are crucial for
      establishing this symbiosis. Alfalfa nodule invasion by S. meliloti can be
      mediated by any one of three symbiotically important polysaccharides:
      succinoglycan, EPS II, or K antigen (also referred to as KPS). Using green
      fluorescent protein-labeled S. meliloti cells, we have shown that there are
      significant differences in the details and efficiencies of nodule invasion
      mediated by these polysaccharides. Succinoglycan is highly efficient in mediating
      both infection thread initiation and extension. However, EPS II is significantly
      less efficient than succinoglycan at mediating both invasion steps, and K antigen
      is significantly less efficient than succinoglycan at mediating infection thread
      extension. In the case of EPS II-mediated symbioses, the reduction in invasion
      efficiency results in stunted host plant growth relative to plants inoculated
      with succinoglycan or K-antigen-producing strains. Additionally, EPS II- and K
      antigen-mediated infection threads are 8 to 10 times more likely to have aberrant
      morphologies than those mediated by succinoglycan. These data have important
      implications for understanding how S. meliloti polysaccharides are functioning in
      the plant-bacterium interaction, and models are discussed.

PMID- 10894744
TI  - Eight of fourteen gvp genes are sufficient for formation of gas vesicles in
      halophilic archaea.
AB  - The minimal number of genes required for the formation of gas vesicles in
      halophilic archaea has been determined. Single genes of the 14 gvp genes present
      in the p-vac region on plasmid pHH1 of Halobacterium salinarum (p-gvpACNO and p
      gvpDEFGHIJKLM) were deleted, and the remaining genes were tested for the
      formation of gas vesicles in Haloferax volcanii transformants. The deletion of
      six gvp genes (p-gvpCN, p-gvpDE, and p-gvpHI) still enabled the production of gas
      vesicles in H. volcanii. The gas vesicles formed in some of these gvp gene
      deletion transformants were altered in shape (Delta I, Delta C) or strength
      (Delta H) but still functioned as flotation devices. A minimal p-vac region
      (minvac) containing the eight remaining genes (gvpFGJKLM-gvpAO) was constructed
      and tested for gas vesicle formation in H. volcanii. The minvac transformants did
      not form gas vesicles; however, minvac/gvpJKLM double transformants contained gas
      vesicles seen as light refractile bodies by phase-contrast microscopy. Transcript
      analyses demonstrated that minvac transformants synthesized regular amounts of
      gvpA mRNA, but the transcripts derived from gvpFGJKLM were mainly short and
      encompassed only gvpFG(J), suggesting that the gvpJKLM genes were not
      sufficiently expressed. Since gvpAO and gvpFGJKLM are the only gvp genes present
      in minvac/JKLM transformants containing gas vesicles, these gvp genes represent
      the minimal set required for gas vesicle formation in halophilic archaea.
      Homologs of six of these gvp genes are found in Anabaena flos-aquae, and homologs
      of all eight minimal halobacterial gvp genes are present in Bacillus megaterium
      and in the genome of Streptomyces coelicolor.

PMID- 10894743
TI  - Identification, evolution, and essentiality of the mevalonate pathway for
      isopentenyl diphosphate biosynthesis in gram-positive cocci.
AB  - The mevalonate pathway and the glyceraldehyde 3-phosphate (GAP)-pyruvate pathway
      are alternative routes for the biosynthesis of the central isoprenoid precursor,
      isopentenyl diphosphate. Genomic analysis revealed that the staphylococci,
      streptococci, and enterococci possess genes predicted to encode all of the
      enzymes of the mevalonate pathway and not the GAP-pyruvate pathway, unlike
      Bacillus subtilis and most gram-negative bacteria studied, which possess only
      components of the latter pathway. Phylogenetic and comparative genome analyses
      suggest that the genes for mevalonate biosynthesis in gram-positive cocci, which
      are highly divergent from those of mammals, were horizontally transferred from a
      primitive eukaryotic cell. Enterococci uniquely encode a bifunctional protein
      predicted to possess both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase and acetyl-CoA acetyltransferase activities. Genetic disruption
      experiments have shown that five genes encoding proteins involved in this pathway
      (HMG-CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate
      kinase, and mevalonate diphosphate decarboxylase) are essential for the in vitro
      growth of Streptococcus pneumoniae under standard conditions. Allelic replacement
      of the HMG-CoA synthase gene rendered the organism auxotrophic for mevalonate and
      severely attenuated in a murine respiratory tract infection model. The mevalonate
      pathway thus represents a potential antibacterial target in the low-G+C gram
      positive cocci.

PMID- 10894745
TI  - Motility and chemotaxis of filamentous cells of Escherichia coli.
AB  - Filamentous cells of Escherichia coli can be produced by treatment with the
      antibiotic cephalexin, which blocks cell division but allows cell growth. To
      explore the effect of cell size on chemotactic activity, we studied the motility
      and chemotaxis of filamentous cells. The filaments, up to 50 times the length of
      normal E. coli organisms, were motile and had flagella along their entire
      lengths. Despite their increased size, the motility and chemotaxis of filaments
      were very similar to those properties of normal-sized cells. Unstimulated
      filaments of chemotactically normal bacteria ran and stopped repeatedly (while
      normal-sized bacteria run and tumble repeatedly). Filaments responded to
      attractants by prolonged running (like normal-sized bacteria) and to repellents
      by prolonged stopping (unlike normal-sized bacteria, which tumble), until
      adaptation restored unstimulated behavior (as occurs with normal-sized cells).
      Chemotaxis mutants that always ran when they were normal sized always ran when
      they were filament sized, and those mutants that always tumbled when they were
      normal sized always stopped when they were filament sized. Chemoreceptors in
      filaments were localized to regions both at the poles and at intervals along the
      filament. We suggest that the location of the chemoreceptors enables the
      chemotactic responses observed in filaments. The implications of this work with
      regard to the cytoplasmic diffusion of chemotaxis components in normal-sized and
      filamentous E. coli are discussed.

PMID- 10894746
TI  - Construction and use of derivatives of transposon Tn4001 that function in
      Mycoplasma pulmonis and Mycoplasma arthritidis.
AB  - Previous attempts to introduce transposon Tn4001 into Mycoplasma pulmonis and
      Mycoplasma arthritidis have not been successful, possibly due to functional
      failure of the transposon's gentamicin resistance determinant. Tn4001C and
      Tn4001T were constructed, respectively, by insertion of a chloramphenicol
      acetyltransferase gene and the tetM tetracycline resistance determinant into
      Tn4001. Both Tn4001C and Tn4001T transposed in M. pulmonis, and Tn4001T
      transposed in M. arthritidis. The incorporation of a Tn4001T derivative that
      contained lacZ into either Mycoplasma species resulted in transformants with
      readily detectable LacZ activity. Tn4001T may be of general utility for use as a
      mycoplasma cloning vehicle because tetM functions in all species of Mycoplasma
      examined thus far.

PMID- 10894747
TI  - Genetic analysis of sliding motility in Mycobacterium smegmatis.
AB  - A screen for nonsliding mutants of Mycobacterium smegmatis yielded 20 mutants
      with transposon insertions in the mps gene, which is involved in
      glycopeptidolipid biosynthesis. One mutant had an insertion in a gene predicted
      to encode a membrane transport protein. All mutants lacked glycopeptidolipids and
      were unable to form biofilms on polyvinyl chloride.

PMID- 10894748
TI  - Identification of a second region of the Spo0A response regulator of Bacillus
      subtilis required for transcription activation.
AB  - Deletion of the 10 C-terminal amino acids of the Bacillus subtilis response
      regulator Spo0A or valine substitution at D258 and L260 resulted in a sporulation
      negative phenotype and loss of in vivo activation of the spoIIG and spoIIA operon
      promoters. Repression of the abrB promoter was not affected by the mutations. In
      combination with the previously characterized mutation (A257V), the results
      identify amino acids at positions 257, 258, and 260 as being required for
      transcription activation by Spo0A.

PMID- 10894749
TI  - Regulation of quorum sensing by RpoS in Pseudomonas aeruginosa.
AB  - The LasR-LasI and RhlR-RhlI quorum-sensing systems are global regulators of gene
      expression in the opportunistic pathogen Pseudomonas aeruginosa. Previous studies
      suggest that the RhlR-RhlI system activates expression of rpoS. We constructed
      merodiploid strains of P. aeruginosa containing the native rpoS gene and an rpoS
      lacZ fusion. Studies of lacZ transcription in these strains indicated that rpoS
      was not regulated by RhlR-RhlI. We also generated an rpoS null mutant. This rpoS
      mutant showed elevated levels of rhlI (but not rhlR) transcription, elevated
      levels of the RhlI-generated acylhomoserine lactone quorum-sensing signal, and
      elevated levels of RhlR-RhlI-regulated gene transcription. These findings
      indicate that there is a relationship between RpoS and quorum sensing, but rather
      than the RhlR-RhlI system influencing the expression of rpoS, it appears that
      RpoS regulates rhlI.

PMID- 10894750
TI  - Prolonged stationary-phase incubation selects for lrp mutations in Escherichia
      coli K-12.
AB  - Evolution by natural selection occurs in cultures of Escherichia coli maintained
      under carbon starvation stress. Mutants of increased fitness express a growth
      advantage in stationary phase (GASP) phenotype, enabling them to grow and
      displace the parent as the majority population. The first GASP mutation was
      identified as a loss-of-function allele of rpoS, encoding the stationary-phase
      global regulator, sigma(S) (M. M. Zambrano, D. A. Siegele, M. A. Almiron, A.
      Tormo, and R. Kolter, Science 259:1757-1760, 1993). We now report that a second
      global regulator, Lrp, can also play a role in stationary-phase competition. We
      found that a mutant that took over an aged culture of an rpoS strain had acquired
      a GASP mutation in lrp. This GASP allele, lrp-1141, encodes a mutant protein
      lacking the critical glycine in the turn of the helix-turn-helix DNA-binding
      domain. The lrp-1141 allele behaves as a null mutation when in single copy and is
      dominant negative when overexpressed. Hence, the mutant protein appears to retain
      stability and the ability to dimerize but lacks DNA-binding activity. We also
      demonstrated that a lrp null allele generated by a transposon insertion has a
      fitness gain identical to that of the lrp-1141 allele, verifying that cells
      lacking Lrp activity have a competitive advantage during prolonged starvation.
      Finally, we tested by genetic analysis the hypothesis that the lrp-1141 GASP
      mutation confers a fitness gain by enhancing amino acid catabolism during carbon
      starvation. We found that while amino acid catabolism may play a role, it is not
      necessary for the lrp GASP phenotype, and hence the lrp GASP phenotype is due to
      more global physiological changes.

PMID- 10894751
TI  - Autoregulation of the Pseudomonas aeruginosa protein PtxS occurs through a
      specific operator site within the ptxS upstream region.
AB  - We have previously shown that the Pseudomonas aeruginosa toxA regulatory protein
      PtxS autoregulates its own synthesis by binding to a 52-bp fragment. The 3' end
      of the 52-bp fragment is located 58 bp 5' of the ptxS translation start site. We
      have identified a 14-bp palindromic sequence (TGAAACCGGTTTCA) within the 52-bp
      fragment. In this study, we used site-directed mutagenesis and promoter fusion
      experiments to determine if PtxS binds specifically to this palindromic sequence
      and regulates ptxS expression. We have also tried to determine the roles of
      specific nucleotides within the palindromic sequence in PtxS binding and ptxS
      expression. Initial promoter fusion experiments confirmed that the 52-bp fragment
      does not overlap with the region that carries the ptxS promoter activity. PtxS
      binding was eliminated upon the deletion of the 14-bp palindromic sequence from
      the 52-bp fragment. In addition, the deletion of the 14-bp sequence caused a
      significant enhancement in ptxS expression in the P. aeruginosa strain PAO1 and
      the ptxS isogenic mutant PAO::ptxS. Mutation of specific nucleotides within the
      14-bp sequence eliminated, reduced, or had no effect on PtxS binding. However,
      mutations of several of these nucleotides produced a significant increase in ptxS
      expression in both PAO1 and PAO::ptxS. These results suggest that (i) the 14-bp
      palindromic sequence and specific nucleotides within it play a role in PtxS
      binding and (ii) deletion of the palindromic sequence or changing of certain
      nucleotides within it interferes with another mechanism that may regulate ptxS
      expression.

PMID- 10894752
TI  - Identification of the Escherichia coli nicotinic acid mononucleotide
      adenylyltransferase gene.
AB  - The gene (ybeN) coding for nicotinate mononucleotide adenylyltransferase, an
      NAD(P) biosynthetic enzyme, has been identified and overexpressed in Escherichia
      coli. This enzyme catalyzes the reversible adenylation of nicotinate
      mononucleotide and shows product inhibition. The rate of adenylation of
      nicotinate mononucleotide is at least 20 times faster than the rate of
      adenylation of nicotinamide mononucleotide.

PMID- 10894753
TI  - To outsource in lead discovery: the devil or the deep blue sea?

PMID- 10894754
TI  - Contract screening: the case against.

PMID- 10894755
TI  - Novel fluorescence sensing methods for high throughput screening.
AB  - We describe two new methods of fluorescence sensing for use in high throughput
      screening (HTS). Modulation sensing transforms analyte-dependent intensity
      changes into a change in the low-frequency modulation signal. Polarization
      sensing transforms an intensity change into a change in polarization. Both
      methods are internally calibrated by using a reference film immediately adjacent
      to the sample, which can be readily located on the HTS plate or on a nearby
      optical component and provides an intensity or polarization reference. Modulation
      sensing and polarization sensing were both shown useful for measurements of
      fluorophore concentrations, pH, or calcium concentrations in the wells of HTS
      plates. Sensing with a reference film provides the opportunity to internally
      reference HTS measurements without the need for additions to the sample. This
      approach can provide standardization for assays performed at different times.

PMID- 10894756
TI  - Large-scale screening assay to measure epidermal growth factor internalization.
AB  - Recently, we showed that the internalization of the epidermal growth factor (EGF)
      receptor is inhibited by hydrogen peroxide (H(2)O(2)) in human fibroblasts. In
      order to test the effect of various stress conditions on receptor internalization
      and to test a variety of antioxidants in their capacity to prevent or reduce the
      H(2)O(2)-induced inhibition of internalization, a screening assay was developed
      to measure the internalization in 96-well plates. In this assay, cells are
      exposed to biotin-conjugated EGF and the amount of internalized EGF is detected
      with horseradish peroxidase-conjugated streptavidin. We show that the results
      obtained by this new assay are comparable with those from internalization studies
      performed with radioactive labeled EGF. Therefore, the cellular internalization
      assay as presented here is a reliable method to measure EGF receptor
      internalization. Moreover, because elaborate processing of the cells is not
      required, the assay is a relatively fast and inexpensive method to study ligand
      induced internalization in 96-well plates and thereby is suitable for large-scale
      screening of compounds or conditions interfering with this internalization.

PMID- 10894757
TI  - Novel fluorescent technology platform for high throughput cytotoxicity and
      proliferation assays.
AB  - We have developed a novel fluorescent Oxygen BioSensor technology platform
      adaptable to many applications in the area of drug discovery and development,
      particularly cell-based assays. This biosensor technology requires no additional
      reagents or incubations, and affords continuous real-time readout of dissolved
      oxygen concentrations. Since the level of oxygen dissolved in an assay's medium
      correlates to the number and viability of the cells in the medium, this
      technology is ideally suited for monitoring cell viability, proliferation, or
      death. The technology is particularly well suited to investigating cells' kinetic
      responses to proliferative or toxic stimuli, such as drugs. When incorporated
      into a 96- or 384-well microplate format, it is compatible with standard
      laboratory automation systems. Here we present data illustrating the application
      of the Oxygen BioSensor technology for rapid, homogeneous detection and
      evaluation of metabolic activity of a variety of eukaryotic and prokaryotic
      cells, including mammalian cells, insect cells, yeast, and bacteria. In the
      absence of toxic substances, we find a good correlation between cell number and
      signal over a wide range of cell concentrations and growth times. To evaluate the
      usefulness of the Oxygen BioSensor for cytotoxicity assays, we have performed a
      series of experiments using a range of toxic agents and cell types, including
      both bacteria and mammalian cell lines. In a side-by-side comparison to standard
      MTT assays using HL60 cells, comparable IC(50) values were found with the Oxygen
      BioSensor for five different toxins or drugs. This assay method does not have the
      need for additional reagents, handling steps, or incubation periods required by
      the MTT assays.

PMID- 10894758
TI  - Development of a high throughput scintillation proximity assay for hepatitis C
      virus NS3 protease that reduces the proportion of competitive inhibitors
      identified.
AB  - A screening assay has been developed for hepatitis C virus (HCV) NS3 protease
      using the scintillation proximity assay (SPA) technology. The sequence of the
      peptide substrate used was taken from the site cleaved by the enzyme in the
      mature nonstructural protein of HCV. The peptide was biotinylated at the N
      terminus and tritiated at the C-terminus so that a decrease in signal was
      detected as a result of enzyme activity. IC(50) values were calculated for the
      cleaved product, and it was shown that the value obtained was dependent on the
      substrate concentration used. The effect of substrate concentration on the
      inhibition of HCV NS3 protease was further highlighted in a mock screening assay,
      using colored natural product samples, in which the hit rate was altered by a
      change in substrate concentration. An increase in substrate concentration reduced
      the proportion of competitive inhibitors identified. This study highlighted the
      importance of optimizing the components used in SPA assays in order to obtain an
      assay format valid for high throughput screening.

PMID- 10894759
TI  - Fluorescence polarization assays for high throughput screening of G protein
      coupled receptors.
AB  - Fluorescence polarization assays in 384-well microtiter plates have been
      demonstrated. The performance is suitable for high throughput drug screening
      applications with respect to speed of analysis, displaceable signal, precision,
      and sensitivity to various reagents. Rank order of potency was maintained
      relative to [(125)I]-ligand filtration assays, and the effects of the highly
      colored compounds, tartrazine and Chicago Sky Blue, were insignificant on the
      polarization signal up to a concentration of 1 microM. These attributes suggest
      that accurate assessment of drug binding can be obtained.

PMID- 10894760
TI  - Development of a cyanovirin-N-HIV-1 gp120 binding assay for high throughput
      screening of natural product extracts by time-resolved fluorescence.
AB  - The unique, high-affinity binding of cyanovirin-N (CV-N), a potent anti-human
      immunodeficiency virus (HIV) protein, to the HIV envelope glycoprotein gp120, was
      exploited to develop an HTS assay in an attempt to discover small-molecule
      mimetics of CV-N. A competition binding assay was developed using CV-N labeled
      with europium (Eu(3+)). The labeling protocol did not significantly alter the
      gp120 binding properties or the antiviral activity of CV-N. This report describes
      the assay development, validation, and results of screening a large library of
      aqueous and organic natural product extracts. The extracts were incubated with
      immobilized recombinant gp120 in 96-well plates prior to the addition of Eu(3+)
      labeled CV-N. Following a wash step, bound CV-N was measured by dissociation
      enhanced time-resolved fluorometry of Eu(3+). The assay proved to be robust,
      rapid, and reproducible, and was used to screen over 50,000 natural product
      extracts, and has resulted in the identification of several aqueous natural
      product extracts that inhibited CV-N-gp120 binding and also had anti-HIV
      activity.

PMID- 10894762
TI  - What if Animal Use in Toxicology was Banned?

PMID- 10894761
TI  - Ultra-high throughput screen of two-million-member combinatorial compound
      collection in a miniaturized, 1536-well assay format.
AB  - Results of a complete survey of the more than 2-million-member Pharmacopeia
      compound collection in a 1536-well microvolume screening assay format are
      reported. A complete technology platform, enabling the performance of ultra-high
      throughput screening in a miniaturized 1536-well assay format, has been assembled
      and utilized. The platform consists of tools for performing microvolume assays,
      including assay plates, liquid handlers, optical imagers, and data management
      software. A fluorogenic screening assay for inhibition of a protease enzyme
      target was designed and developed using this platform. The assay was used to
      perform a survey screen of the Pharmacopeia compound collection for active
      inhibitors of the target enzyme. The results from the survey demonstrate the
      successful implementation of the ultra-high throughout platform for routine
      screening purposes. Performance of the assay in the miniaturized format is
      equivalent to that of a standard 96-well assay, showing the same dependence on
      kinetic parameters and ability to measure enzyme inhibition. The survey screen
      identified an active class of compounds within the Pharmacopeia compound
      collection. These results were confirmed using a standard 96-well assay.

PMID- 10894763
TI  - Cytotoxicity of MEIC Chemicals Nos. 11-30 in 3T3 Mouse Fibroblasts with and
      without Microsomal Activation.
AB  - The cytotoxicity of MEIC chemicals Nos. 11-30 was evaluated by determination of
      neutral red uptake in Balb/c 3T3 mouse fibroblasts with and without the addition
      of a microsomal activation mixture. The use of microsomes significantly decreased
      the cytotoxicity of malathion, 2,4-dichlorophenoxyacetic acid, propranolol,
      thioridazine, lithium sulfate, copper sulfate and thallium sulfate, whereas the
      cytotoxicity of 1,1,1-trichloroethylene, phenol, nicotine, and paraquat was
      significantly increased by use of the microsomal activation mixture. These
      cytotoxicity data are in line with observations in other studies on microsomal
      modulation of the cytotoxicity of the test substances. Moderate to good
      correlations were found between the cytotoxicity data and rodent lethality data,
      and the addition of microsomes slightly improved the in vitro/in vivo
      concordance. The evidence to support the relevance of the in vitro/in vivo
      correlations obtained in the MEIC project is limited due to a high variability on
      the in vivo lethality data and a large interlaboratory variation on the in vitro
      data.

PMID- 10894764
TI  - Analysis of the Transforming Potential of Growth and Differentiation Factors in
      Syrian Hamster Embryo Cells: Reversible and Irreversible Transformation.
AB  - The mitogenic growth and differentiation factor (GDFs) oncostatin M (OM),
      epidermal growth factor (EGF), fibroblast growth factor 4 (FGF-4), platelet
      derived growth factor AA (PDGF AA), PDGF AB, and PDGF BB and the anti-mitogenic
      GDF, transforming growth factor beta one (TGF-beta1), were tested in the 7-day
      continuous exposure and 24-h transient exposure Syrian hamster embryo (SHE) cell
      transformation assay to determine their reversible and irreversible transforming
      potential. OM was negative while EGF, FGF-4, and PDGF AA were positive for
      statistically significant morphological transformation (MT) in the 7-day exposure
      SHE cell transformation assay. PDGF AB and PDGF BB (but not EGF, FGF-4, and PDGF
      AA) were positive for statistically significant MT in the 24-h transient exposure
      SHE cell transformation assays. TGF-beta1 was not only negative for the induction
      of MT in the 7-day and 24-h exposure SHE cell transformation assays, but
      suppressed the spontaneous background transformation response. Investigation of
      the transformation suppression potential of TGF-beta1 demonstrated that TGF-beta1
      was able to irreversibly suppress the transformation potential of a variety of
      transforming agents including growth factors, Ames assay positive carcinogens,
      and Ames assay negative carcinogens. PDGF AA and PDGF BB were investigated to
      better understand the reversible and irreversible transformation response.
      Differences in the receptors activated, the proteins phosphorylated by the
      receptors, and immediate early gene expressed were observed in SHE cells treated
      with either PDGF AA or PDGF BB. Importantly, SHE cells treated with TGF-beta1 and
      PDGF BB, two GDFs, which modulate SHE cell transformation irreversibly, altered
      DNA methylation; PDGF AA did not demonstrate this effect. Together these data
      demonstrate that the SHE cell transformation assay can be utilized to evaluate
      the transformation potential and mechanism of activation of GDFs.

PMID- 10894765
TI  - Superinduction of Oxidized Tryptophan-Inducible Cytochrome P450 1A1 by
      Cycloheximide in Hepa lclc7 Cells.
AB  - Previous studies from this laboratory have shown that L-tryptophan, after
      oxidation by either ultraviolet (UV) irradiation or ozone, causes induction of
      cytochrome P450 (CYP)1A1 mRNA, protein, and the corresponding 7-ethoxyresorufin O
      deethylase (EROD) activity in wild type mouse hepatoma cells, Hepa lclc7 (Hepa
      1), through the aryl hydrocarbon receptor (AhR). In the present study, we have
      examined the effect of temporary inhibition of protein synthesis by cycloheximide
      on oxidized tryptophan inducible CYP1A1 mRNA, protein, and EROD activity in Hepa
      1 cells. The results demonstrate that combined exposure of wild-type Hepa-1 cells
      to either UV- or ozone-oxidized tryptophan and cycloheximide causes an increase
      in CYP1A1 mRNA, protein, and EROD activity, which is greater than the sum of the
      increases that were observed by exposure to each compound alone. The increase in
      EROD activity is dependent upon the dose and duration of cycloheximide treatment
      and is prolonged by actinomycin D when the latter compound was administered after
      removal of cycloheximide. Studies carried out to investigate the mechanism of
      this superinduction using various mutants of Hepa-1 cells, which are defective in
      either the AhR or AhR nuclear translocator protein indicated that the
      superinduction of oxidized tryptophan inducible EROD activity by cycloheximide
      occurs through the AhR. This is the first demonstration that oxidized tryptophan,
      in the presence of cycloheximide, causes superinduction of transcription of the
      Cyp1a1 gene with concomitant increase of CYP1A1 protein and EROD activity in Hepa
      1 cells.

PMID- 10894766
TI  - Vitamin E and EDTA Improve the Efficacy of Hypothermosol-Implication of
      Apoptosis.
AB  - The emergence of engineered tissues and new cell strains has called for the need
      to explore solutions that can be used to store these cells and tissues in a state
      of near suspended animation without using cryopreservation. The ability of the
      hypothermic solutions ViaSpan (DuPont Merck Pharmaceutical Company, Wilmington,
      DE), HypoThermosol (Cryomedical Sciences, Rockville, MD), HypoThermosol
      supplemented with either ethylenediaminetetraacetic acid (EDTA) or Vitamin E and
      HypoThermosol supplemented with apoptosis protease inhibitors were tested for
      their abilities to cold-protect Madin Darby Canine Kidney (MDCK) cells at 4
      degrees C. Alamar Blue, a nontoxic metabolic indicator was used to measure cell
      viability. The order of cold protection was HypoThermosol with Vitamin E and EDTA
      > HypoThermosol with Vitamin E > HypoThermosol with EDTA > HypoThermosol >
      ViaSpan > Dulbecco's Modified Eagle's Medium (DMEM). Membrane integrity tests
      supported the Alamar Blue data that EDTA and Vitamin E conferred a benefit to the
      cold-storage capabilities of HypoThermosol. MDCK cells that died subsequent to 1
      to 6 days cold-storage detached from the substratum and their DNA was harvested
      after being placed at 37 degrees C. This DNA was compared to DNA retrieved from
      adherent cells in the same cultures that survived the cold-storage regime. Gel
      electrophoresis of cells dying due to 1 to 4 days of cold-storage showed a DNA
      ladder indicating that cells died through apoptosis, programmed cell death. Dead
      cells harvested at 5 to 6 days of cold storage, however, had randomly cleaved DNA
      indicative of necrotic cell death. HypoThermosol supplemented with apoptosis
      protease inhibitors was better able to cold-protect cells than the base
      HypoThermosol. These data suggest that the inhibition of apoptosis should be
      considered in the future cold-storage formulations.

PMID- 10894767
TI  - Glutamate Release from Chick Retina Explants in Response to Domoic Acid.
AB  - Release of endogenous glutamate (GLU) evoked by an exogenous excitotoxin such as
      kainate can contribute to central nervous system (CNS) excitotoxicity. In this
      study, the possibility that this mechanism accounts for reported domoic acid
      (DOM) toxicity was investigated using the isolated chick retina. Exposing retinas
      to 0-100 uM DOM for 40 min caused an increased efflux of lactate dehydrogenase
      (LDH) and a dose-related release of GLU into the incubation medium. Neuronal
      damage following exposure to DOM was confirmed by histologic examination of the
      retina. DOM-induced GLU release occurred at 27 and 37 degrees C and was more
      pronounced in medium containing a low calcium concentration (0.1 mM). In
      contrast, K(+) evoked GLU release occurred only at 37 degrees C in 2 mM calcium,
      but not at 27 degrees C. DOM-induced GLU release was reduced in hyperosmolar
      medium (medium 1 100 mM sucrose). Similar to GLU release, the LDH release
      occurred at both 27 and 37 degrees C and was reduced in hyperosmolar medium.
      These results suggest that an increase in membrane permeability secondary to
      osmotic swelling and lysis rather than a calcium-dependent vesicular exocytosis
      mechanism is responsible for GLU and LDH release. GYKI 52466, a selective
      noncompetitive antagonist of the non-NMDA receptor, prevented neuronal
      degeneration and GLU/LDH release. MK-801, a highly potent noncompetitive NMDA
      receptor blocker, reduced neuronal injury (33% decrease in LDH release), but did
      not reduce DOM-evoked GLU release significantly. Typical excitotoxic lesions were
      produced at all concentrations tested, with amacrine cells in the inner nuclear
      layer being the most severely affected. Released GLU contributed to further
      excitotoxic injury, exacerbating the neurotoxic action of DOM in isolated
      embryonic chick retina.

PMID- 10894768
TI  - CAATSCAN: A Review of Alternatives News and Information.

PMID- 10894769
TI  - Role of the mouse ank gene in control of tissue calcification and arthritis.
AB  - Mutation at the mouse progressive ankylosis (ank) locus causes a generalized,
      progressive form of arthritis accompanied by mineral deposition, formation of
      bony outgrowths, and joint destruction. Here, we show that the ank locus encodes
      a multipass transmembrane protein (ANK) that is expressed in joints and other
      tissues and controls pyrophosphate levels in cultured cells. A highly conserved
      gene is present in humans and other vertebrates. These results identify ANK
      mediated control of pyrophosphate levels as a possible mechanism regulating
      tissue calcification and susceptibility to arthritis in higher animals.

PMID- 10894770
TI  - Causes of climate change over the past 1000 years
AB  - Recent reconstructions of Northern Hemisphere temperatures and climate forcing
      over the past 1000 years allow the warming of the 20th century to be placed
      within a historical context and various mechanisms of climate change to be
      tested. Comparisons of observations with simulations from an energy balance
      climate model indicate that as much as 41 to 64% of preanthropogenic (pre-1850)
      decadal-scale temperature variations was due to changes in solar irradiance and
      volcanism. Removal of the forced response from reconstructed temperature time
      series yields residuals that show similar variability to those of control runs of
      coupled models, thereby lending support to the models' value as estimates of low
      frequency variability in the climate system. Removal of all forcing except
      greenhouse gases from the approximately 1000-year time series results in a
      residual with a very large late-20th-century warming that closely agrees with the
      response predicted from greenhouse gas forcing. The combination of a unique level
      of temperature increase in the late 20th century and improved constraints on the
      role of natural variability provides further evidence that the greenhouse effect
      has already established itself above the level of natural variability in the
      climate system. A 21st-century global warming projection far exceeds the natural
      variability of the past 1000 years and is greater than the best estimate of
      global temperature change for the last interglacial.

PMID- 10894771
TI  - Signature of superfluid density in the single-particle excitation spectrum of
      Bi(2)Sr(2)CaCu(2)O(8+delta)
AB  - We report that the doping and temperature dependence of photoemission spectra
      near the Brillouin zone boundary of Bi(2)Sr(2)CaCu(2)O(8+delta)exhibit unexpected
      sensitivity to the superfluid density. In the superconducting state, the
      photoemission peak intensity as a function of doping scales with the superfluid
      density and the condensation energy. As a function of temperature, the peak
      intensity shows an abrupt behavior near the superconducting phase transition
      temperature where phase coherence sets in, rather than near the temperature where
      the gap opens. This anomalous manifestation of collective effects in single
      particle spectroscopy raises important questions concerning the mechanism of high
      temperature superconductivity.

PMID- 10894772
TI  - Dispersive multiplexing in multimode optical fiber
AB  - Recently developed ideas in the field of wireless communications suggest that the
      presence of scattering can be used to enhance, rather than degrade, the total
      information capacity of a transmission system. This concept is applied to data
      transmission over multimode optical fiber, and the result is an optical
      multiplexing that can increase the capacity of such fiber. Experimental results
      demonstrate the feasibility of this approach. The technique may play an important
      role in future high-bandwidth local area networking applications.

PMID- 10894773
TI  - Global water resources: vulnerability from climate change and population growth.
AB  - The future adequacy of freshwater resources is difficult to assess, owing to a
      complex and rapidly changing geography of water supply and use. Numerical
      experiments combining climate model outputs, water budgets, and socioeconomic
      information along digitized river networks demonstrate that (i) a large
      proportion of the world's population is currently experiencing water stress and
      (ii) rising water demands greatly outweigh greenhouse warming in defining the
      state of global water systems to 2025. Consideration of direct human impacts on
      global water supply remains a poorly articulated but potentially important facet
      of the larger global change question.

PMID- 10894774
TI  - Overpressure and fluid flow in the new jersey continental slope: implications for
      slope failure and cold seeps
AB  - Miocene through Pleistocene sediments on the New Jersey continental slope (Ocean
      Drilling Program Site 1073) are undercompacted (porosity between 40 and 65%) to
      640 meters below the sea floor, and this is interpreted to record fluid pressures
      that reach 95% of the lithostatic stress. A two-dimensional model, where rapid
      Pleistocene sedimentation loads permeable sandy silt of Miocene age, successfully
      predicts the observed pressures. The model describes how lateral pressure
      equilibration in permeable beds produces fluid pressures that approach the
      lithostatic stress where overburden is thin. This transfer of pressure may cause
      slope failure and drive cold seeps on passive margins around the world.

PMID- 10894775
TI  - Timing the radiations of leaf beetles: hispines on gingers from latest cretaceous
      to recent.
AB  - Stereotyped feeding damage attributable solely to rolled-leaf hispine beetles is
      documented on latest Cretaceous and early Eocene ginger leaves from North Dakota
      and Wyoming. Hispine beetles (6000 extant species) therefore evolved at least 20
      million years earlier than suggested by insect body fossils, and their
      specialized associations with gingers and ginger relatives are ancient and
      phylogenetically conservative. The latest Cretaceous presence of these relatively
      derived members of the hyperdiverse leaf-beetle clade (Chrysomelidae, more than
      38,000 species) implies that many of the adaptive radiations that account for the
      present diversity of leaf beetles occurred during the Late Cretaceous,
      contemporaneously with the ongoing rapid evolution of their angiosperm hosts.

PMID- 10894776
TI  - ORCA3, a jasmonate-responsive transcriptional regulator of plant primary and
      secondary metabolism.
AB  - Biosynthesis of many classes of secondary metabolites in plants is induced by the
      stress hormone jasmonate. The gene for ORCA3, a jasmonate-responsive APETALA2
      (AP2)-domain transcription factor from Catharanthus roseus, was isolated by
      transferred DNA activation tagging. Orca3 overexpression resulted in enhanced
      expression of several metabolite biosynthetic genes and, consequently, in
      increased accumulation of terpenoid indole alkaloids. Regulation of metabolite
      biosynthetic genes by jasmonate-responsive AP2-domain transcription factors may
      link plant stress responses to changes in metabolism.

PMID- 10894777
TI  - An inherited functional circadian clock in zebrafish embryos.
AB  - Circadian clocks are time-keeping systems found in most organisms. In zebrafish,
      expression of the clock gene Period3 (Per3) oscillates throughout embryogenesis
      in the central nervous system and the retina. Per3 rhythmic expression was free
      running and was reset by light but not by the developmental delays caused by low
      temperature. The time of fertilization had no effect on Per3 expression. Per3
      messenger RNA accumulates rhythmically in oocytes and persists in embryos. Our
      results establish that the circadian clock functions during early embryogenesis
      in zebrafish. Inheritance of maternal clock gene products suggests a mechanism of
      phase inheritance through ovogenesis.

PMID- 10894778
TI  - Requirement of the spindle checkpoint for proper chromosome segregation in
      budding yeast meiosis.
AB  - The spindle checkpoint was characterized in meiosis of budding yeast. In the
      absence of the checkpoint, the frequency of meiosis I missegregation increased
      with increasing chromosome length, reaching 19% for the longest chromosome.
      Meiosis I nondisjunction in spindle checkpoint mutants could be prevented by
      delaying the onset of anaphase. In a recombination-defective mutant (spo11Delta),
      the checkpoint delays the biochemical events of anaphase I, suggesting that
      chromosomes that are attached to microtubules but are not under tension can
      activate the spindle checkpoint. Spindle checkpoint mutants reduce the accuracy
      of chromosome segregation in meiosis I much more than that in meiosis II,
      suggesting that checkpoint defects may contribute to Down syndrome.

PMID- 10894779
TI  - An anti-apoptotic role for the p53 family member, p73, during developmental
      neuron death.
AB  - p53 plays an essential pro-apoptotic role, a function thought to be shared with
      its family members p73 and p63. Here, we show that p73 is primarily present in
      developing neurons as a truncated isoform whose levels are dramatically decreased
      when sympathetic neurons apoptose after nerve growth factor (NGF) withdrawal.
      Increased expression of truncated p73 rescues these neurons from apoptosis
      induced by NGF withdrawal or p53 overexpression. In p73-/- mice, all isoforms of
      p73 are deleted and the apoptosis of developing sympathetic neurons is greatly
      enhanced. Thus, truncated p73 is an essential anti-apoptotic protein in neurons,
      serving to counteract the pro-apoptotic function of p53.

PMID- 10894780
TI  - Evidence for mating of the "asexual" yeast Candida albicans in a mammalian host.
AB  - Since its classification nearly 80 years ago, the human pathogen Candida albicans
      has been designated as an asexual yeast. In this report, we describe the
      construction of C. albicans strains that were subtly altered at the mating-type
      like (MTL) locus, a cluster of genes that resembles the mating-type loci of other
      fungi. These derivatives were capable of mating after inoculation into a
      mammalian host. C. albicans is a diploid organism, but most of the mating
      products isolated from a mouse host were tetrasomic for the two chromosomes that
      could be rigorously monitored and, overall, exhibited substantially higher than
      2n DNA content. These observations demonstrated that C. albicans can recombine
      sexually.

PMID- 10894781
TI  - Induction of mating in Candida albicans by construction of MTLa and MTLalpha
      strains.
AB  - Although the diploid fungus Candida albicans, a human pathogen, has been thought
      to have no sexual cycle, it normally possesses mating-type-like orthologs (MTL)
      of both of the Saccharomyces cerevisiae mating-type genes (MAT) a and alpha. When
      strains containing only MTLa or MTLalpha were constructed by the loss of one
      homolog of chromosome 5, the site of the MTL loci, MTLa and MTLalpha strains
      mated, but like mating types did not. Evidence for mating included formation of
      stable prototrophs from strains with complementing auxotrophic markers; these
      contained both MTL alleles and molecular markers from both parents and were
      tetraploid in DNA content and mononucleate.

PMID- 10894782
TI  - Induction and maintenance of the neuronal cholinergic phenotype in the central
      nervous system by BMP-9.
AB  - Bone morphogenetic proteins (BMPs) have multiple functions in the developing
      nervous system. A member of this family, BMP-9, was found to be highly expressed
      in the embryonic mouse septum and spinal cord, indicating a possible role in
      regulating the cholinergic phenotype. In cultured neurons, BMP-9 directly induced
      the expression of the cholinergic gene locus encoding choline acetyltransferase
      and the vesicular acetylcholine transporter and up-regulated acetylcholine
      synthesis. The effect was reversed upon withdrawal of BMP-9.
      Intracerebroventricular injection of BMP-9 increased acetylcholine levels in
      vivo. Although certain other BMPs also up-regulated the cholinergic phenotype in
      vitro, they were less effective than BMP-9. These data indicate that BMP-9 is a
      differentiating factor for cholinergic central nervous system neurons.

PMID- 10894783
TI  - Acute renal failure. III. The role of growth factors in the process of renal
      regeneration and repair.
AB  - This review, which is the final installment in a series devoted to controversial
      issues in acute renal failure (ARF) (3, 47), will examine available information
      regarding the role of growth factors in ARF. In general, studies in this area
      have fallen into two broad categories: 1) those that have examined the renal
      expression of genes encoding growth factors or transcriptional factors associated
      with the growth response that is induced after ARF, and 2) those that have
      examined the efficacy of exogenously administered growth factors in accelerating
      recovery of renal function in experimental models of ARF. Despite the vast amount
      of information that has accumulated in these two areas of investigation, our
      understanding of the mechanisms involved in the process of regeneration and
      repair after ARF, and the role of growth factors in this response, remains
      rudimentary. This overview, contributed to by a number of experts in the field,
      is designed to summarize present knowledge and to highlight potentially fertile
      areas for future research in this area.

PMID- 10894784
TI  - Prostaglandin E receptors and the kidney.
AB  - Prostaglandin E(2) is a major renal cyclooxygenase metabolite of arachidonate and
      interacts with four G protein-coupled E-prostanoid receptors designated EP(1),
      EP(2), EP(3), and EP(4). Through these receptors, PGE(2) modulates renal
      hemodynamics and salt and water excretion. The intrarenal distribution and
      function of EP receptors have been partially characterized, and each receptor has
      a distinct role. EP(1) expression predominates in the collecting duct where it
      inhibits Na(+) absorption, contributing to natriuresis. The EP(2) receptor
      regulates vascular reactivity, and EP(2) receptor-knockout mice have salt
      sensitive hypertension. The EP(3) receptor is also expressed in vessels as well
      as in the thick ascending limb and collecting duct, where it antagonizes
      vasopressin-stimulated salt and water transport. EP(4) mRNA is expressed in the
      glomerulus and collecting duct and may regulate glomerular tone and renal renin
      release. The capacity of PGE(2) to bidirectionally modulate vascular tone and
      epithelial transport via constrictor EP(1) and EP(3) receptors vs. dilator EP(2)
      and EP(4) receptors allows PGE(2) to serve as a buffer, preventing excessive
      responses to physiological perturbations.

PMID- 10894785
TI  - A mathematical model of the outer medullary collecting duct of the rat.
AB  - A mathematical model of the outer medullary collecting duct (OMCD) has been
      developed, consisting of alpha-intercalated cells and a paracellular pathway, and
      which includes Na(+), K(+), Cl(-), HCO(3)(-), CO(2), H(2)CO(3), phosphate,
      ammonia, and urea. Proton secretion across the luminal cell membrane is mediated
      by both H(+)-ATPase and H-K-ATPase, with fluxes through the H-K-ATPase given by a
      previously developed kinetic model (Weinstein AM. Am J Physiol Renal Physiol 274:
      F856-F867, 1998). The flux across each ATPase is substantial, and variation in
      abundance of either pump can be used to control OMCD proton secretion. In
      comparison with the H(+)-ATPase, flux through the H-K-ATPase is relatively
      insensitive to changes in lumen pH, so as luminal acidification proceeds, proton
      secretion shifts toward this pathway. Peritubular HCO(3)(-) exit is via a
      conductive pathway and via the Cl(-)/HCO(3)(-) exchanger, AE1. To represent AE1,
      a kinetic model has been developed based on transport studies obtained at 38
      degrees C in red blood cells. (Gasbjerg PK, Knauf PA, and Brahm J. J Gen Physiol
      108: 565-575, 1996; Knauf PA, Gasbjerg PK, and Brahm J. J Gen Physiol 108: 577
      589, 1996). Model calculations indicate that if all of the chloride entry via AE1
      recycles across a peritubular chloride channel and if this channel is anything
      other than highly selective for chloride, then it should conduct a substantial
      fraction of the bicarbonate exit. Since both luminal membrane proton pumps are
      sensitive to small changes in cytosolic pH, variation in density of either AE1 or
      peritubular anion conductance can modulate OMCD proton secretory rate. With
      respect to the OMCD in situ, available buffer is predicted to be abundant,
      including delivered HCO(3)(-) and HPO(4)(2-), as well as peritubular NH(3). Thus,
      buffer availability is unlikely to exert a regulatory role in total proton
      secretion by this tubule segment.

PMID- 10894786
TI  - Vasopressin-mediated regulation of epithelial sodium channel abundance in rat
      kidney.
AB  - Sodium transport is increased by vasopressin in the cortical collecting ducts of
      rats and rabbits. Here we investigate, by quantitative immunoblotting, the
      effects of vasopressin on abundances of the epithelial sodium channel (ENaC)
      subunits (alpha, beta, and gamma) in rat kidney. Seven-day infusion of 1-deamino
      [8-D-arginine]-vasopressin (dDAVP) to Brattleboro rats markedly increased whole
      kidney abundances of beta- and gamma-ENaC (to 238% and 288% of vehicle,
      respectively), whereas alpha-ENaC was more modestly, yet significantly, increased
      (to 142% of vehicle). Similarly, 7-day water restriction in Sprague-Dawley rats
      resulted in significantly increased abundances of beta- and gamma- but no
      significant change in alpha-ENaC. Acute administration of dDAVP (2 nmol) to
      Brattleboro rats resulted in modest, but significant, increases in abundance for
      all ENaC subunits, within 1 h. In conclusion, all three subunits of ENaC are
      upregulated by vasopressin with temporal and regional differences. These changes
      are too slow to play a major role in the short-term action of vasopressin to
      stimulate sodium reabsorption in the collecting duct. Long-term increases in ENaC
      abundance should add to the short-term regulatory mechanisms (undefined in this
      study) to enhance sodium transport in the renal collecting duct.

PMID- 10894787
TI  - The transport properties of the human renal Na(+)- dicarboxylate cotransporter
      under voltage-clamp conditions.
AB  - The transport properties of the human Na(+)-dicarboxylate cotransporter, (hNaDC
      1), expressed in Xenopus laevis oocytes were characterized using the two
      electrode voltage clamp technique. Steady-state succinate-evoked inward currents
      in hNaDC-1 were dependent on the concentrations of succinate and sodium, and on
      the membrane potential. At -50 mV, the half-saturation constant for succinate
      (K(0.5)(succinate)) was 1.1 mM and the half-saturation constant for sodium
      (K(0.5)(sodium)) was 65 mM. The Hill coefficient was 2.3, which is consistent
      with a transport stoichiometry of 3 Na(+):1 divalent anion substrate. The hNaDC-1
      exhibits a high-cation selectivity. Sodium is the preferred cation and other
      cations, such as lithium, were not able to support transport of succinate. The
      preferred substrates of hNaDC-1 are fumarate (K(0.5) 1.8 mM) and succinate,
      followed by methylsuccinate (K(0.5) 2.8 mM), citrate (K(0. 5) 6.8 mM) and alpha
      ketoglutarate (K(0.5) 16 mM). The hNaDC-1 may also transport sodium ions through
      an uncoupled leak pathway, which is sensitive to phloretin inhibition. We propose
      a transport model for hNaDC-1 in which the binding of three sodium ions is
      followed by substrate binding.

PMID- 10894788
TI  - Metanephrogenic mesenchyme-to-epithelium transition induces profound expression
      changes of ion channels.
AB  - The expression patterns of plasma membrane transporters that specify the
      epithelial cell type are acquired with ontogeny. To study this process during
      metanephrogenic mesenchyme-to-epithelium transition, branching ureteric buds with
      their adjacent mesenchymal blastema (mouse embryonic day E14) were dissected and
      explanted on a collagen matrix. In culture, induced mesenchymal cells condensed,
      aggregated, and converted to the comma- and S-shaped body. During in vitro
      condensation and aggregation, transcription factor Pax-2 protein was
      downregulated while the epithelial markers E-cadherin and beta-catenin proteins
      were upregulated. In addition, Wilms' tumor suppressor protein WT-1 was
      detectable upon condensation and downregulated in the S stage, where expression
      persisted in the long arm of the S. Patch-clamp, whole cell conductance (G, in
      nS/10 pF) of pre-epithelial condensed mesenchymal cells (n = 7) was compared with
      that of tubular proximal S-shaped-body epithelium (n = 6). Both stages expressed
      E-cadherin and WT-1 mRNA, as demonstrated by single-cell RT-PCR, testifying
      further to the epithelial as well as the nephrogenic commitment of the recorded
      cells. Mesenchymal cells exhibited whole cell currents (G = 6.7 +/- 1.3) with
      reversal potentials (V(rev), in mV) near equilibrium potential for Cl(-) (E(Cl))
      (V(rev) = -40 +/- 7) suggestive of a high fractional Cl(-) conductance. Currents
      of the S-shaped-body cells (G = 4.0 +/- 1.1), in sharp contrast, had a V(rev) at
      E(K) (V(rev) = -82 +/- 6) indicating a high fractional K(+) conductance. Further,
      analysis of K(+)-selective whole cell tail currents and single-channel recording
      revealed a change in K(+) channel expression. Also, Kir6.1 K(+) channel mRNA and
      protein were downregulated between both stages, whereas K(v)LQT K(+) channel mRNA
      was abundant throughout. In conclusion, metanephrogenic mesenchyme-to-epithelium
      transition is accompanied by a profound reorganization of plasma membrane ion
      channel conductance.

PMID- 10894789
TI  - L-Dopa uptake and dopamine production in proximal tubular cells are regulated by
      beta(2)-adrenergic receptors.
AB  - This study assessed the role of adrenergic receptors on the regulation of the
      uptake of L-dopa and the production of dopamine by renal tubular cells. Scatchard
      analysis showed two L-dopa uptake sites with different affinities (K(m) 0.316 vs
      1.53 microM). L-Dopa uptake was decreased by the nonselective adrenergic agonists
      epinephrine or norepinephrine (40%), by the beta-selective agonist isoproterenol
      or the beta(2)-selective agonist terbutaline (60%), but not by alpha-selective
      agonists (all 1 microM). The effect of norepinephrine, isoproterenol, or
      terbutaline was unaffected by addition of the beta(1)-antagonist atenolol,
      abolished by ICI-118, 551, a beta(2)-antagonist (both 0.1 microM), and mimicked
      by the addition of dibutyryl-cAMP (1 microM). Preincubation with terbutaline
      decreased the number of high-affinity uptake sites (V(max) = 1.10 +/- 0.3 vs. 0.5
      +/- 0.1 pmol. mg protein(-1). min(-1)) without changing their affinity.
      Norepinephrine or terbutaline decreased dopamine production by isolated cells,
      and this effect was abolished by ICI-118,551 (0.1 microM). In vivo administration
      of ICI-118,551 reduced the urinary excretion of L-dopa and increased the
      excretion of 3,4-dihydroxyphenylacetic acid without significant changes in plasma
      L-dopa concentrations. These results demonstrate that stimulation of beta(2)
      adrenergic receptors decreases the number of high-affinity L-dopa uptake sites in
      isolated tubular cells resulting in a reduction of the uptake of L-dopa and the
      production of dopamine and provide evidence for the presence of this mechanism in
      the intact animal.

PMID- 10894790
TI  - Glomerular size and charge selectivity in the rat as revealed by FITC-ficoll and
      albumin.
AB  - The fractional clearances (theta) for FITC-Ficoll and albumin were estimated in
      isolated perfused rat kidneys in which the tubular activity was inhibited by low
      temperature (8 degrees C) and/or 10 mM NH(4)Cl. The Ficoll data were analyzed
      according to a two-pore model giving small and large pore radii of 46 A and 80-87
      A, respectively. The estimated negative charge density was 35-45 meq/l at 8
      degrees C. Perfusion with erythrocyte-free solutions of kidneys at 37 degrees C
      reduced glomerular size and charge permselectivity. Thus the large pore fraction
      of the glomerular filtrate (f(L)) was 1.64% at 37 degrees C compared with 0.94%
      at 8 degrees C. The theta for albumin was four times higher at 37 degrees C than
      at 8 degrees C (0.86% vs. 0.19%, respectively). NH(4)Cl caused further
      irreversible damage to the glomerular barrier. We conclude that there are no
      deleterious effects on the glomerular barrier of a reduction in temperature from
      37 degrees C to 8 degrees C. Therefore our data seem to disprove the hypothesis
      of low glomerular permselectivity and transtubular uptake of intact albumin and
      support the classic concept of a highly selective glomerular barrier.

PMID- 10894791
TI  - Extracellular ATP increases [CA(2+)](i) in distal tubule cells. I. Evidence for a
      P2Y2 purinoceptor.
AB  - Experiments were performed to characterize the P2 purinoceptor subtype
      responsible for cytoplasmic calcium mobilization in cells from the initial part
      of rabbit distal convoluted tubule (DCT). Free calcium concentration was measured
      in a DCT cell line (DC1) with the probe fura 2. Both ATP and UTP increased
      cytosolic Ca(2+) concentration ([Ca(2+)](i); EC(50) 3 and 6 microM,
      respectively). The order of potency for nucleotide analogs was ATP = UTP >
      adenosine 5'-O-[thiotriphosphate] >> ADP > UDP, which is consistent with the
      pharmacology of the P2Y2 receptor subtype. The increased [Ca(2+)](i) responses to
      ATP and UTP were strongly inhibited by suramin. Pretreatment of cells with
      pertussis toxin (PTX) attenuated the action of both nucleotides. Inhibition of
      phospholipase C with U-73122 totally blocked the [Ca(2+)](i) response to ATP.
      Thus ATP- and UTP-stimulated [Ca(2+)](i) mobilization in DC1 cells appears to be
      mediated via the activation of P2Y2 purinoceptors coupled to a G protein
      mechanism that is partially sensitive to PTX. Calcium flux measurements showed
      that lanthanum- and nifedipine-sensitive calcium channels are involved in the
      [Ca(2+)](i) response to ATP.

PMID- 10894792
TI  - Extracellular ATP increases [Ca(2+)](i) in distal tubule cells. II. Activation of
      a Ca(2+)-dependent Cl(-) conductance.
AB  - We characterized Cl(-) conductance activated by extracellular ATP in an
      immortalized cell line derived from rabbit distal bright convoluted tubule (DC1).
      (125)I(-) efflux experiments showed that ATP increased (125)I(-) loss with an
      EC(50) = 3 microM. Diphenylamine-2-carboxylate (10(-3) M) and NPPB (10(-4) M)
      abolished the (125)I(-) efflux. Preincubation with 10 microM 1, 2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester or 10(-7) M
      thapsigargin inhibited the effect of ATP. Ionomycin (2 microM) increased (125)I(
      ) efflux with a time course similar to that of extracellular ATP, suggesting that
      the response is dependent on the intracellular Ca(2+) concentration
      ([Ca(2+)](i)). The ATP agonist potency order was ATP >/= UTP > ATPgammaS. Suramin
      (500 microM) inhibited the ATP-induced (125)I(-) efflux, consistent with P2
      purinoceptors. (125)I(-) effluxes from cells grown on permeable filters suggest
      that ATP induced an apical efflux that was mediated via apical P2 receptors.
      Whole cell experiments showed that ATP (100 microM) activated outwardly
      rectifying Cl(-) currents in the presence of 8-cyclopentyl-1,3-dipropylxanthine,
      excluding the involvement of P1 receptors. Ionomycin activated Cl(-) currents
      similar to those developed with ATP. These results demonstrate the presence of a
      purinergic regulatory mechanism involving ATP, apical P2Y2 receptors, and Ca(2+)
      mobilization for apical Cl(-) conductance in a distal tubule cell line.

PMID- 10894793
TI  - Increased renal medullary endothelin-1 synthesis in prehypertensive DOCA- and
      salt-treated rats.
AB  - To investigate the role of renal endothelin-1 (ET-1) synthesis in water-sodium
      homeostasis, we measured mRNA expressions, protein levels, enzyme activity, and
      receptor binding of the renal ET-1 system in a DOCA- and salt-treated rat model.
      Male Wistar rats were divided into control and DOCA- and salt-treated (DOCA-Salt)
      groups. The DOCA-Salt group received 25 mg/kg body wt DOCA and was maintained on
      1% NaCl drinking water. Rats were killed on days 1, 2, 4, and 10 of the
      experiment. Urinary ET-1-like immunoreactivity significantly increased from the
      second day in the DOCA-Salt group and correlated well with the urinary sodium
      excretion rate (r = 0.81, P < 0.001). Renal endothelin-converting enzyme (ECE)
      activity, ET-1, and ECE-1 mRNA expressions were significantly increased in the
      renal medullary area of DOCA-Salt rats. In situ hybridization and
      immunohistochemical studies showed that the increase in ET-1 synthesis was mainly
      localized in the inner medullary collecting ducts. The maximum binding of
      endothelin B receptor also increased from the second day in the renal medulla of
      the DOCA-Salt group. Our results suggest that renal medullary synthesized ET-1
      may be a natriuretic factor and may participate in the intrarenal regulation of
      water and salt homeostasis in prehypertensive DOCA-and salt-treated rats.

PMID- 10894794
TI  - Nitric oxide regulates renal cortical cyclooxygenase-2 expression.
AB  - We have previously shown that cyclooxygenase-2 (COX-2) is localized to the
      cortical thick ascending limb of the loop of Henle (cTALH)/macula densa of the
      rat kidney, and expression increases in response to low-salt diet and/or
      angiotensin-converting enzyme (ACE) inhibition. Because of the localization of
      neuronal nitric oxide synthase (nNOS) to macula densa and surrounding cTALH, the
      present study investigated the role of nitric oxide (NO) in the regulation of COX
      2 expression. For in vivo studies, rats were fed a normal diet, low-salt diet or
      low-salt diet combined with the ACE inhibitor captopril. In each group, one-half
      of them were treated with the nNOS inhibitors 7-nitroinidazole (7-NI) or S-methyl
      thiocitrulline. Both of these NOS inhibitors inhibited increases in COX-2 mRNA
      and immunoreactive protein in response to low salt and low salt+captopril. For in
      vitro studies, COX-2 expression was studied in primary cultures of rabbit cTALH
      cells immunodisssected with Tamm-Horsfall antibody. Basal COX-2 immunoreactivity
      expression was stimulated by S-nitroso-N-acetyl-penicillamine (SNAP), an NO
      donor, and intracellular cGMP concentration. The cultured cells expressed
      immunoreactive nNOS, and 7-NI inhibited basal COX-2 immunoreactivity expression,
      which could be partially overcome by cGMP. In summary, these studies indicate
      that NO is a mediator of increased renal cortical COX-2 expression seen in volume
      depletion and suggest important interactions between the NO and COX-2 systems in
      the regulation of arteriolar tone and the renin-angiotensin system by the macula
      densa.

PMID- 10894795
TI  - Osteogenic protein-1 prevents renal fibrogenesis associated with ureteral
      obstruction.
AB  - Unilateral ureteral obstruction (UUO) is a model of renal injury characterized by
      progressive tubulointerstitial fibrosis and renal damage, while relatively
      sparing the glomerulus and not producing hypertension or abnormalities in lipid
      metabolism. Tubulointerstitial fibrosis is a major component of several kidney
      diseases associated with the progression to end-stage renal failure. Here we
      report that when a critical renal developmental morphogen, osteogenic protein-1
      (OP-1; 100 or 300 microg/kg body wt), is administered at the time of UUO and
      every other day thereafter, interstitial inflammation and fibrogenesis are
      prevented, leading to preservation of renal function during the first 5 days
      after obstruction. Compared with angiotensin-converting enzyme inhibition with
      enalapril treatment, OP-1 was more effective in preventing tubulointerstitial
      fibrosis and in preserving renal function. The mechanism of OP-1- induced renal
      protection was associated with prevention of tubular atrophy, an effect not
      shared with enalapril, and was related to preservation of tubular epithelial
      integrity. OP-1 blocked the stimulation of epithelial cell apoptosis produced by
      UUO, which promoted maintenance of tubular epithelial integrity. OP-1 preserved
      renal blood flow (RBF) during UUO, but enalapril also stimulated RBF. Thus OP-1
      treatment inhibited tubular epithelial disruption stimulated by the renal injury
      of UUO, preventing tubular atrophy and diminishing the activation of
      tubulointerstitial inflammation and fibrosis and preserving renal function.

PMID- 10894796
TI  - Downregulation of aquaporin-2 and -3 in aging kidney is independent of V(2)
      vasopressin receptor.
AB  - The mechanisms underlying age-related polyuria were investigated in 10- and 30-mo
      old female WAG/Rij rats. Urinary volume and osmolality were 3.9 +/- 0.3 ml/24 h
      and 2,511 +/- 54 mosmol/kgH(2)O in adult rats and 12.8 +/- 0.8 ml/24 h and 1,042
      +/- 44 mosmol/kgH(2)O in senescent animals. Vasopressin V(2) receptor mRNA did
      not significantly differ between 10 and 30 mo, and [(3)H]vasopressin binding
      sites in membrane papilla were reduced by 30%. The cAMP content of the papilla
      was unchanged with age, whereas papillary osmolality was significantly lowered in
      senescent animals. The expression of aquaporin-1 (AQP1) and -4 was mostly
      unaltered from 10 to 30 mo. In contrast, aquaporin-2 (AQP2) and -3 (AQP3)
      expression was downregulated by 80 and 50%, respectively, and AQP2 was markedly
      redistributed into the intracellular compartment, in inner medulla of senescent
      animals, but not in renal cortex. These results indicate that age-related
      polyuria is associated with a downregulation of AQP2 and AQP3 expression in the
      medullary collecting duct, which is independent of vasopressin-mediated cAMP
      accumulation.

PMID- 10894797
TI  - Activation of H(+)-K(+)-ATPase by CO(2) requires a basolateral Ba(2+)-sensitive
      pathway during K restriction.
AB  - We studied the activation of H(+)-K(+)-ATPase by CO(2) in the renal cortical
      collecting duct (CCD) of K-restricted animals. Exposure of microperfused CCD to
      10% CO(2) increased net total CO(2) flux (J(t CO(2))) from 4.9 +/- 2.1 to 14.7 +/
      4 pmol. mm(-1). min(-1) (P < 0. 05), and this effect was blocked by luminal
      application of the H(+)-K(+)-ATPase inhibitor Sch-28080. In the presence of
      luminal Ba, a K channel blocker, exposure to CO(2) still stimulated J(t CO(2))
      from 6.0 +/- 1.0 to 16.8 +/- 2.8 pmol. mm(-1). min(-1) (P < 0.01), but
      peritubular application of Ba inhibited the stimulation. CO(2) substantially
      increased (86)Rb efflux (a K tracer marker) from 93.1 +/- 23.8 to 249 +/- 60.2
      nm/s (P < 0.05). These observations suggest that during K restriction 1) the
      enhanced H(+)-K(+)-ATPase-mediated acidification after exposure to CO(2) is
      dependent on a basolateral Ba-sensitive mechanism, which is different from the
      response of rabbits fed a normal-K diet, where activation of the H(+)-K(+)-ATPase
      by exposure to CO(2) is dependent on an apical Ba-sensitive pathway; and 2) K/Rb
      absorption via the apical H(+)-K(+)-ATPase exits through a basolateral Ba
      sensitive pathway. Together, these data are consistent with the hypothesis of
      cooperation between H(+)-K(+)-ATPase-mediated acidification and K exit pathways
      in the CCD that regulate K homeostasis.

PMID- 10894798
TI  - Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model
      for ions and diuretics interaction.
AB  - The thiazide-sensitive Na(+)-Cl(-) cotransporter (TSC) is the major pathway for
      salt reabsorption in the apical membrane of the mammalian distal convoluted
      tubule. When expressed in Xenopus laevis oocytes, rat TSC exhibits high affinity
      for both cotransported ions, with the Michaelis-Menten constant (K(m)) for Na(+)
      of 7.6 +/- 1.6 mM and for Cl(-) of 6.3 +/- 1.1 mM, and Hill coefficients for
      Na(+) and Cl(-) consistent with electroneutrality. The affinities of both Na(+)
      and Cl(-) were increased by increasing concentration of the counterion. The
      IC(50) values for thiazides were affected by both extracellular Na(+) and Cl(-).
      The higher the Na(+) or Cl(-) concentration, the lower the inhibitory effect of
      thiazides. Finally, rTSC function is affected by extracellular osmolarity. We
      propose a transport model featuring a random order of binding in which the
      binding of each ion facilitates the binding of the counterion. Both ion binding
      sites alter thiazide-mediated inhibition of transport, indicating that the
      thiazide-binding site is either shared or modified by both Na(+) and Cl(-).

PMID- 10894799
TI  - Store-operated calcium influx inhibits renin secretion.
AB  - On the basis of evidence that changes in the extracellular concentration of
      calcium effectively modulate renin secretion from renal juxtaglomerular cells,
      our study aimed to determine the effect of calcium influx activated by depletion
      of intracellular calcium stores on renin secretion. For this purpose we
      characterized the effects of the endoplasmatic Ca(2+)-ATPase inhibitors
      thapsigargin (300 nM) and cyclopiazonic acid (20 microM) on renin secretion from
      isolated perfused rat kidneys. We found that Ca(2+)-ATPase inhibition caused a
      potent inhibition of basal renin secretion as well as renin secretion activated
      by isoproterenol, bumetanide, and by a fall in the renal perfusion pressure. The
      inhibitory effect of Ca(2+)-ATPase inhibition on renin secretion was reversed
      within seconds by lowering of the extracellular calcium concentration into the
      submicromolar range but was not affected by lanthanum, gadolinium, flufenamic
      acid, or amlodipine. These data suggest that calcium influx triggered by release
      of calcium from internal stores is a powerful mechanism to inhibit renin
      secretion from juxtaglomerular cells. The store-triggered calcium influx pathway
      in juxtaglomerular cells is apparently not sensitive to classic blockers of the
      capacitative calcium entry pathway.

PMID- 10894800
TI  - Cloning of mesangial cell Na(+)/Ca(2+) exchangers from Dahl/Rapp salt
      sensitive/resistant rats.
AB  - The Dahl/Rapp rat model of hypertension is characterized by a marked increase in
      blood pressure and a progressive fall in glomerular filtration rate when salt
      sensitive (S) rats are placed on an 8% NaCl diet. On the same diet, the salt
      resistant (R) rat does not exhibit these changes. In previous studies we found
      that protein kinase C (PKC) upregulates Na(+)/Ca(2+) exchanger activity in
      afferent arterioles and mesangial cells from R but not S rats. One possible
      reason for the difference in PKC sensitivity may be due to differences in the S
      and R Na(+)/Ca(2+) exchanger protein. We now report the cloning of Na(+)/Ca(2+)
      exchangers from R (RNCX1) and S (SNCX1) mesangial cells. At the amino acid level,
      SNCX1 differs from RNCX1 at position 218 in the NH(2)-terminal domain where it is
      isoleucine in RNCX1 but phenylalanine in SNCX1. These two exchangers also differ
      by 23 amino acids at the alternative splice site within the cytosolic domain.
      RNCX1 and SNCX1 were expressed in OK-PTH cells and (45)Ca(2+)-uptake studies were
      performed. Acute phorbol 12-myristate 13-acetate (PMA) treatment (300 nM, 20 min)
      upregulated exchanger activity in cells expressing RNCX1 but failed to stimulate
      exchanger activity in SNCX1 expressing cells. Upregulation of RNCX1 could be
      prevented by prior 24-h pretreatment with PMA, which downregulates PKC. These
      results demonstrate a difference in PKC-Na(+)/Ca(2+) exchange activity between
      the isoform of the exchanger cloned from the R vs. the S rat. Lack of PKC
      activation of SNCX1 may contribute to a dysregulation of intracellular Ca(2+)
      concentration and enhanced renal vasoreactivity in this model of hypertension.

PMID- 10894801
TI  - Cellular localization of type 5 and type 6 ACs in collecting duct and regulation
      of cAMP synthesis.
AB  - The cellular distribution of Ca(2+)-inhibitable adenylyl cyclase (AC) type 5 and
      type 6 mRNAs in rat outer medullary collecting duct (OMCD) was performed by in
      situ hybridization. Kidney sections were also stained with specific antibodies
      against either collecting duct intercalated cells or principal cells. The
      localization of type 5 AC in H(+)-ATPase-, but not aquaporin-3-, positive cells
      demonstrated that type 5 AC mRNA is expressed only in intercalated cells. In
      contrast, type 6 AC mRNA was observed in both intercalated and principal cells.
      In microdissected OMCDs, the simultaneous superfusion of carbachol and PGE(2)
      elicited an additive increase in the intracellular Ca(2+) concentration,
      suggesting that the Ca(2+)-dependent regulation of these agents occurs in
      different cell types. Glucagon-dependent cAMP synthesis was inhibited by both a
      pertussis toxin-sensitive PGE(2) pathway (63.7 +/- 4.6% inhibition, n = 5) and a
      Ca(2+)-dependent carbachol pathway (48.6 +/- 3.3%, n = 5). The simultaneous
      addition of both agents induced a cumulative inhibition of glucagon-dependent
      cAMP synthesis (78.2 +/- 3.3%, n = 5). The results demonstrate a distinct
      cellular localization of type 5 and type 6 AC mRNAs in OMCD and the functional
      expression of these Ca(2+)-inhibitable enzymes in intercalated cells.

PMID- 10894803
TI  - TP or not TP: primary mediators in a close runoff?

PMID- 10894802
TI  - Potassium depletion increases proton pump (H(+)-ATPase) activity in intercalated
      cells of cortical collecting duct.
AB  - Intercalated cells (ICs) from kidney collecting ducts contain proton-transporting
      ATPases (H(+)-ATPases) whose plasma membrane expression is regulated under a
      variety of conditions. It has been shown that net proton secretion occurs in the
      distal nephron from chronically K(+)-depleted rats and that upregulation of
      tubular H(+)- ATPase is involved in this process. However, regulation of this
      protein at the level of individual cells has not so far been examined. In the
      present study, H(+)-ATPase activity was determined in individually identified ICs
      from control and chronically K(+)-depleted rats (9-14 days on a low-K(+) diet) by
      monitoring K(+)- and Na(+)-independent H(+) extrusion rates after an acute acid
      load. Split-open rat cortical collecting tubules were loaded with the
      intracellular pH (pH(i)) indicator 2', 7'-bis(2-carboxyethyl)-5(6)
      carboxyfluorescein, and pH(i) was determined by using ratiometric fluorescence
      imaging. The rate of pH(i) recovery in ICs in response to an acute acid load, a
      measure of plasma membrane H(+)-ATPase activity, was increased after K(+)
      depletion to almost three times that of controls. Furthermore, the lag time
      before the start of pH(i) recovery after the cells were maximally acidified fell
      from 93.5 +/- 13.7 s in controls to 24.5 +/- 2.1 s in K(+)-depleted rats. In all
      ICs tested, Na(+)- and K(+)-independent pH(i) recovery was abolished in the
      presence of bafilomycin (100 nM), an inhibitor of the H(+)-ATPase. Analysis of
      the cell-to-cell variability in the rate of pH(i) recovery reveals a change in
      the distribution of membrane-bound proton pumps in the IC population of cortical
      collecting duct from K(+)-depleted rats. Immunocytochemical analysis of
      collecting ducts from control and K(+)-depleted rats showed that K(+)-depletion
      increased the number of ICs with tight apical H(+)ATPase staining and decreased
      the number of cells with diffuse or basolateral H(+)-ATPase staining. Taken
      together, these data indicate that chronic K(+) depletion induces a marked
      increase in plasma membrane H(+)ATPase activity in individual ICs.

PMID- 10894804
TI  - Toward new therapeutic strategies against neointimal formation in restenosis.

PMID- 10894805
TI  - AIF-1 in the activated smooth muscle cell : spectator or participant?

PMID- 10894806
TI  - Homocysteine and its disulfide derivatives: a suggested consensus terminology.

PMID- 10894807
TI  - Nitric oxide regulation of free radical- and enzyme-mediated lipid and
      lipoprotein oxidation.
AB  - The regulation of nonenzymatic and enzymatic lipid oxidation reactions by nitric
      oxide (.NO) is potent and pervasive and reveals novel non-cGMP-dependent
      reactivities for this free radical inflammatory and signal transduction
      mediator.NO and its metabolites stimulate and inhibit lipid peroxidation
      reactions, modulate enzymatically catalyzed lipid oxidation, complex with lipid
      reactive metals, and alter proinflammatory gene expression. Through these
      mechanisms,.NO can regulate nonenzymatic lipid oxidation and the production of
      inflammatory and vasoactive eicosanoids by prostaglandin endoperoxide synthase
      and lipoxygenase. The accumulation of macrophages and oxidized low density
      lipoprotein within the vascular wall can also be modulated by.NO. A key
      determinant of the pro-oxidant versus oxidant-protective influences of.NO is the
      underlying oxidative status of tissue. When.NO is in excess of surrounding
      oxidants, lipid oxidation and monocyte margination into the vascular wall are
      attenuated, producing antiatherogenic effects. However, when endogenous tissue
      rates of oxidant production are accelerated or when tissue oxidant defenses
      become depleted,.NO gives rise to secondary oxidizing species that can increase
      membrane and lipoprotein lipid oxidation as well as foam cell formation in the
      vasculature, thus promoting proatherogenic effects. In summary,.NO is a
      multifaceted molecule capable of reacting via multiple pathways to modulate lipid
      oxidation reactions, thereby impacting on tissue inflammatory reactions.

PMID- 10894808
TI  - Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction
      pathways and antioxidant protection.
AB  - Oxidative modification of low density lipoprotein (LDL) appears to play an
      important role in atherogenesis. Although the precise mechanisms of LDL oxidation
      in vivo are unknown, several lines of evidence implicate myeloperoxidase and
      reactive nitrogen species, in addition to ceruloplasmin and 15-lipoxygenase.
      Myeloperoxidase generates a number of reactive species, including hypochlorous
      acid, chloramines, tyrosyl radicals, and nitrogen dioxide. These reactive species
      oxidize the protein, lipid, and antioxidant components of LDL. Modification of
      apolipoprotein B results in enhanced uptake of LDL by macrophages with subsequent
      formation of lipid-laden foam cells. Nitric oxide synthases produce nitric oxide
      and, under certain conditions, superoxide radicals. Numerous other sources of
      superoxide radicals have been identified in the arterial wall, including NAD(P)H
      oxidases and xanthine oxidase. Nitric oxide and superoxide readily combine to
      form peroxynitrite, a reactive nitrogen species capable of modifying LDL. In this
      review, we examine the reaction pathways involved in LDL oxidation by
      myeloperoxidase and reactive nitrogen species and the potential protective
      effects of the antioxidant vitamins C and E.

PMID- 10894809
TI  - The thromboxane receptor antagonist S18886 but not aspirin inhibits atherogenesis
      in apo E-deficient mice: evidence that eicosanoids other than thromboxane
      contribute to atherosclerosis.
AB  - Atherosclerosis involves a complex array of factors, including leukocyte adhesion
      and platelet vasoactive factors. Aspirin, which is used to prevent secondary
      complications of atherosclerosis, inhibits platelet production of thromboxane
      (Tx) A(2). The actions of TxA(2) as well as of other arachidonic acid products,
      such as prostaglandin (PG) H(2), PGF(2alpha), hydroxyeicosatetraenoic acids, and
      isoprostanes, can be effectively antagonized by blocking thromboxane (TP)
      receptors. The purpose of this study was to determine the role of platelet
      derived TxA(2) in atherosclerotic lesion development by comparing the effects of
      aspirin and the TP receptor antagonist S18886. The effect of 11 weeks of
      treatment with aspirin (30 mg. kg(-1). d(-1)) or S18886 (5 mg. kg(-1). d(-1)) on
      aortic root atherosclerotic lesions, serum levels of intercellular adhesion
      molecule-1 (ICAM-1), and the TxA(2) metabolite TxB(2) was determined in
      apolipoprotein E-deficient mice at 21 weeks of age. Both treatments did not
      affect body or heart weight or serum cholesterol levels. Aspirin, to a greater
      extent than S18886, significantly decreased serum TxB(2) levels, indicating the
      greater efficacy of aspirin in preventing platelet synthesis of TxA(2). S18886,
      but not aspirin, significantly decreased aortic root lesions as well as serum
      ICAM-1 levels. S18886 also prevented the increased expression of ICAM-1 in
      cultured human endothelial cells stimulated by the TP receptor agonist U46619.
      These results indicate that inhibition of platelet TxA(2) synthesis with aspirin
      has no significant effect on atherogenesis or adhesion molecule levels. The
      effects of S18886 suggest that blockade of TP receptors inhibits atherosclerosis
      by a mechanism independent of platelet-derived TxA(2), perhaps by preventing the
      expression of adhesion molecules whose expression is stimulated by eicosanoids
      other than TxA(2).

PMID- 10894810
TI  - Monoclonal antibody against vascular cell adhesion molecule-1 inhibits neointimal
      formation after periadventitial carotid artery injury in genetically
      hypercholesterolemic mice.
AB  - Vascular cell adhesion molecule (VCAM)-1 is induced in smooth muscle cells after
      arterial injury, in which it has been implicated in the recruitment of
      inflammatory cells to the site of injury. To investigate the effect of
      hypercholesterolemia on VCAM-1 induction after injury and the role of VCAM-1 in
      neointimal response to injury, we injured the carotid artery of wild-type and
      apolipoprotein E null (KO) mice fed normal and high cholesterol chow. We
      demonstrate a graded response of VCAM-1 induction as well as monocyte/macrophage
      infiltration by immunohistochemistry 3 days after injury that correlated with
      increasing circulating cholesterol levels. Three weeks after injury, KO mice fed
      high cholesterol chow (KO HC group) had a significantly greater neointimal
      formation compared with wild-type and KO mice fed normal chow (P<0.05).
      Inhibition of VCAM-1 function in the KO HC group by monoclonal antibody treatment
      significantly reduced monocyte/macrophage infiltration and neointimal formation.
      There was reduced alpha-actin expression in KO HC mice 7 days after injury that
      was partially inhibited by VCAM-1 antibody treatment. Cell migration in an in
      vitro injury model was partially inhibited by monoclonal VCAM-1 antibody
      treatment. We propose an additional role for VCAM-1 in smooth muscle cell
      activation and neointimal formation after injury.

PMID- 10894811
TI  - Expression of allograft inflammatory factor-1 is a marker of activated human
      vascular smooth muscle cells and arterial injury.
AB  - The cytokine-induced activation and proliferation of medial vascular smooth
      muscle cells (VSMCs) leading to intimal hyperplasia is one of the most critical
      cellular events in the formation of transplant arteriopathy and balloon
      angioplasty-induced restenosis. Allograft inflammatory factor-1 (AIF-1) is a
      calcium-binding protein that we have previously shown to be expressed in balloon
      angioplasty-injured rat carotid arteries. We hypothesized that AIF-1 expression
      may be associated with the VSMC response to injury. In this study, we examined
      AIF-1 expression in immunologic and mechanical models of arterial injury. Reverse
      transcription-polymerase chain reaction and Western analysis demonstrated that
      AIF-1 is acutely and transiently expressed in aortic medial smooth muscle cells
      of rat cardiac allografts, with mRNA and protein peaking at 3 to 7 days after
      transplant and declining by 10 days after transplant. Immunohistochemical
      analysis identified abundant AIF-1 in the medial VSMCs of these vessels.
      Immunohistochemical analysis of balloon angioplasty-injured swine coronary
      arteries also demonstrates an acute AIF-1 expression detectable by 24 hours and
      continuing up to 14 days after the procedure. AIF-1 in these vessels also
      localizes to the medial VSMCs and cells of the developing neointima. AIF-1
      protein is not expressed in quiescent cultured human VSMCs but is induced in
      cells challenged with various inflammatory cytokines, primarily by interferon
      gamma, interleukin-1beta, and T-cell-conditioned media. Transfection and
      overexpression of AIF-1 in human VSMCs result in enhanced growth of these cells.
      Taken together, these data indicate that AIF-1 expression is associated with
      vascular trauma and suggest that this protein may play a role in VSMC activation
      subsequent to arterial injury.

PMID- 10894812
TI  - Involvement of aldose reductase in vascular smooth muscle cell growth and lesion
      formation after arterial injury.
AB  - Abnormal proliferation of vascular smooth muscle cells (VSMCs) is an important
      feature of atherosclerosis, restenosis, and hypertension. Although multiple
      mediators of VSMC growth have been identified, few effective pharmacological
      tools have been developed to limit such growth. Recent evidence indicating an
      important role for oxidative stress in cell growth led us to investigate the
      potential role of aldose reductase (AR) in the proliferation of VSMCs. Because AR
      catalyzes the reduction of mitogenic aldehydes derived from lipid peroxidation,
      we hypothesized that it might be a potential regulator of redox changes that
      accompany VSMC growth. Herein we report several lines of evidence suggesting that
      AR facilitates/mediates VSMC growth. Stimulation of human aortic SMCs in culture
      with mitogenic concentrations of serum, thrombin, basic fibroblast growth factor,
      and the lipid peroxidation product 4-hydroxy-trans-2-nonenal (HNE) led to a 2- to
      4-fold increase in the steady-state levels of AR mRNA, a 4- to 7-fold increase in
      AR protein, and a 2- to 3-fold increase in its catalytic activity. Inhibition of
      the enzyme by sorbinil or tolrestat diminished mitogen-induced DNA synthesis and
      cell proliferation. In parallel experiments, the extent of reduction of the
      glutathione conjugate of HNE to glutathionyl-1,4-dihydroxynonene in HNE-exposed
      VSMCs was decreased by serum starvation or sorbinil. Immunohistochemical staining
      of cross sections from balloon-injured rat carotid arteries showed increased
      expression of AR protein associated with the neointima. The media of injured or
      uninjured arteries demonstrated no significant staining. Compared with untreated
      animals, rats fed sorbinil (40 mg. kg(-1). d(-1)) displayed a 51% and a 58%
      reduction in the ratio of neointima to the media at 10 and 21 days, respectively,
      after balloon injury. Taken together, these findings suggest that AR is
      upregulated during growth and that this upregulation facilitates growth by
      enhancing the metabolism of secondary products of reactive oxygen species.

PMID- 10894813
TI  - Multiple connexin expression in regenerating arterial endothelial gap junctions.
AB  - Endothelial cells form gap junctions that, according to vessel type, may be
      composed of up to 3 types of connexin, connexin37, connexin40, and connexin43.
      Although changes in connexin expression have been linked to growth and injury in
      cultured endothelial cells, information on connexin expression in regenerating
      endothelium in situ is lacking. We investigated gap junction distribution and
      expression of all 3 endothelial connexins during healing in rat carotid artery
      after denudation injury. En face viewing of the vascular luminal surface by means
      of immunoconfocal microscopy was used to examine the spatial and temporal
      expression pattern of the endothelial connexins. Gap junction spots labeled by
      specific antisera against connexin37, connexin40, and connexin43 were quantified
      7, 14, and 28 days after injury, and the relations among the connexins were
      examined by using colocalization analysis. Complementary electron microscopy was
      also conducted. After injury, the regenerating endothelium initially expressed
      small, sparse gap junctions, the numbers of which progressively increased to
      values equivalent to those of controls. Although connexin40 gap-junctional spot
      size and area returned to uninjured levels by 28 days after injury, connexin37
      and connexin43 spot size and area exceeded those of the uninjured artery
      (P<0.05). Double-label analysis showed that even though colocalization of
      connexins to the same gap-junctional spot is a common feature, the extent of
      colocalization was time dependent (>80% in the intact artery at postinjury day 28
      and <70% at postinjury days 7 and 14, P<0.01). We conclude that distinct
      alterations in expression of the 3 connexins are associated with regeneration of
      the arterial endothelium in situ, implying different intercellular communication
      requirements during the various phases of the healing process.

PMID- 10894814
TI  - Assembly of multimeric von Willebrand factor directs sorting of P-selectin.
AB  - We designed a model system to study the role of von Willebrand factor (vWF) in
      the sorting of P-selectin and the biogenesis of Weibel-Palade body (WPB)-like
      organelles. For that purpose, a human epithelial cell line (T24) that synthesizes
      P-selectin mRNA, but which is devoid of vWF mRNA synthesis and storage
      organelles, was transfected with full-length vWF cDNA or a deletion mutant
      thereof. Stable transfectants of T24 with full-length vWF cDNA revealed the
      generation of WPB-like organelles as demonstrated by colocalization of vWF and P
      selectin with double-labeling immunofluorescence. In contrast, T24 cells
      transfected with vWF delD'D3 cDNA, encoding a mutant that is unable to form vWF
      multimers, displayed only perinuclear vWF staining, whereas no indication was
      found for the presence of WPB-like organelles. The contents of the organelles in
      full-length vWF cDNA-transfected T24 cells were released on activation of the
      protein kinase C pathway, similar to the situation with genuine endothelial
      cells. The expression of vWF did not affect the biosynthesis of P-selectin, as
      deduced from the observation that untransfected and vWF cDNA-transfected T24
      cells contained the same amount of P-selectin mRNA. We propose that the
      biosynthesis of multimeric vWF directs the generation of WPB-like organelles, as
      evidenced by the sequestering and anchoring of P-selectin into these storage
      granules.

PMID- 10894815
TI  - Enrichment of acyl coenzyme A:cholesterol O-acyltransferase near trans-golgi
      network and endocytic recycling compartment.
AB  - Acyl coenzyme A:cholesterol O-acyltransferase (ACAT) is the enzyme responsible
      for cholesterol esterification in macrophages leading to foam cell formation. The
      determination of its localization is a critical step in understanding its
      regulation by cholesterol. Using immunofluorescence and confocal microscopy, we
      previously showed that the enzyme colocalized with markers of the endoplasmic
      reticulum, but in addition, ACAT was found in an unidentified paranuclear site.
      In the present study, we further define the localization of paranuclear ACAT.
      First, we found that ACAT does not colocalize with sorting endosomes or late
      endosomes labeled with fluorescent alpha(2)-macroglobulin. The paranuclear ACAT
      is close to the endocytic recycling compartment labeled with fluorescent
      transferrin. We also show that the paranuclear structure containing ACAT is very
      close to TGN38, a membrane protein of the trans-Golgi network (TGN), but farther
      from Gos28, a marker of cis, medial, and trans Golgi. After treatment with
      nocodazole, the central localization of ACAT did not colocalize with markers of
      the TGN. These data indicate that a significant fraction of ACAT resides in
      membranes that may be a subcompartment of the endoplasmic reticulum in proximity
      to the TGN and the endocytic recycling compartment. Because the TGN and the
      endocytic recycling compartment are engaged in extensive membrane traffic with
      the plasma membrane, esterification of cholesterol in these membranes may play an
      important role in macrophage foam cell formation during atherogenesis.

PMID- 10894816
TI  - Interleukin-6 stimulates LDL receptor gene expression via activation of sterol
      responsive and Sp1 binding elements.
AB  - Inflammatory or malignant diseases are associated with elevated levels of
      cytokines and abnormal low density lipoprotein (LDL) cholesterol metabolism. In
      the acute-phase response to myocardial injury or other trauma or surgery, total
      and LDL cholesterol levels are markedly decreased. We investigated the effects of
      the proinflammatory cytokine interleukin (IL)-6 on LDL receptor (LDL-R) function
      and gene expression in HepG2 cells. IL-6 dose-dependently increased the binding,
      internalization, and degradation of (125)I-LDL. IL-6-stimulated HepG2 cells
      revealed increased steady-state levels of LDL-R mRNA. In HepG2 cells transiently
      transfected with reporter gene constructs harboring the sequence of the LDL-R
      promoter extending from nucleotide -1563 (or from nucleotide -234) through -58
      relative to the translation start site, IL-6 dose-dependently increased promoter
      activity. In the presence of LDL, a similar relative stimulatory effect of IL-6
      was observed. Studies using a reporter plasmid with a functionally disrupted
      sterol-responsive element (SRE)-1 revealed a reduced stimulatory response to IL
      6. In gel-shift assays, nuclear extracts of IL-6-treated HepG2 cells showed an
      induced binding of SRE binding protein (SREBP)-1a and SRE binding protein(SREBP)
      2 to the SRE-1 that was independent of the cellular sterol content and an induced
      binding of Sp1 and Sp3 to repeat 3 of the LDL-R promoter. Our data indicate that
      IL-6 induces stimulation of the LDL-R gene, resulting in enhanced gene
      transcription and LDL-R activity. This effect is sterol independent and involves,
      on the molecular level, activation of nuclear factors binding to SRE-1 and the
      Sp1 binding site in repeat 2 and repeat 3 of the LDL-R promoter, respectively.

PMID- 10894817
TI  - A functional polymorphism in the promoter region of the microsomal triglyceride
      transfer protein (MTP -493G/T) influences lipoprotein phenotype in familial
      hypercholesterolemia.
AB  - The microsomal triglyceride transfer protein (MTP) has a key function in
      intracellular apolipoprotein (apo) B lipidation and secretion of very low density
      lipoprotein (VLDL). A recently discovered functional polymorphism in the promoter
      of the MTP gene (-493G/T) affects the plasma concentration of low density
      lipoprotein (LDL) cholesterol and the VLDL distribution between large and small
      particle species in healthy men. This phenotype is likely to be explained by an
      effect on VLDL synthesis. Against this background, we studied the effect of the
      MTP-493G/T polymorphism in a large cohort (217 men and 211 women) with
      heterozygous familial hypercholesterolemia (FH). A 40% to 50% lower serum
      triglyceride level was observed in homozygous carriers of the MTP-493 T allele
      (T/T, 0.93+/-0.34; G/T, 1.54+/-1.40; and G/G, 1.56+/-1.24 mmol/L; T/T vs G/T
      P=0.04, T/T vs G/G P=0.02). In contrast to the situation in healthy subjects, the
      MTP promoter polymorphism did not have a significant effect on the LDL
      cholesterol levels in FH subjects, although the same trend was observed (T/T,
      7.31+/-1.87; G/T, 7. 80+/-2.12; and G/G, 7.91+/-2.31 mmol/L, NS). Adjustment for
      the apo E gene polymorphism by inclusion of subjects homozygous for the apo E3
      allele only revealed a reciprocal high density lipoprotein cholesterol-elevating
      effect (T/T, 1.41+/-0.73; G/T, 1.18+/-0.27; and G/G, 1.16+/-0.29 mmol/L; T/T vs
      G/T P=0.06, T/T vs G/G P=0.04). This effect seemed to be sex-specific because it
      was accounted for by the female patients. In conclusion, the LDL cholesterol
      lowering effect of the rare MTP gene promoter variant (MTP-493T) present in
      healthy subjects is shifted to a triglyceride-lowering effect in FH. These data
      suggest that the MTP gene has a role in modulating the clinical phenotype of FH.

PMID- 10894818
TI  - G-250A substitution in promoter of hepatic lipase gene is associated with
      dyslipidemia and insulin resistance in healthy control subjects and in members of
      families with familial combined hyperlipidemia.
AB  - Low activity of hepatic lipase (HL) has been associated with high levels of
      triglycerides and high density lipoproteins, but the association of the HL
      promoter variants with insulin sensitivity has not been investigated. Therefore,
      in this study, the relationship of the G-250A promoter variant of the HL gene to
      the rates of insulin-stimulated glucose uptake measured by the hyperinsulinemic
      euglycemic clamp was investigated in 110 control subjects (82 men and 28 women,
      aged 50.7+/-7.6 [mean+/-SD] years, body mass index 26. 1+/-3.6 kg/m(2)) and in
      105 first-degree relatives (65 men and 40 women, aged 47.8+/-16.0 years, body
      mass index 26.9+/-5.3 kg/m(2)) of 34 families with familial combined
      hyperlipidemia (FCHL). The A-250 allele of the HL promoter was associated with
      low rates of insulin-stimulated whole-body nonoxidative glucose disposal in
      control subjects (41.1+/-12.7 micromol. kg(-1). min(-1) in subjects with the G
      250G genotype, 36.9+/-13.1 micromol. kg(-1). min(-1) in subjects with the G-250A
      genotype, and 29.9+/-13.5 micromol. kg(-1). min(-1) in subjects with the A-250A
      genotype; P=0.012 adjusted for age and sex) and with low rates of insulin
      stimulated whole-body glucose oxidation in FCHL family members (16.7+/-4.2 versus
      15.0+/-4. 4 versus 14.1+/-4.4 micromol. kg(-1). min(-1), P=0.024). In addition,
      the A-250 allele was associated with high levels of fasting insulin (P=0.047),
      very low density lipoprotein cholesterol (P=0.007), and total (P=0.009) and very
      low density lipoprotein (P=0.005) triglycerides in control subjects and with high
      levels of low density lipoprotein triglycerides (P=0.001) in FCHL family members
      (n=340). We conclude that the G-250A promoter variant of the HL gene is
      associated with dyslipidemia and insulin resistance. Mechanisms via which this
      polymorphism could affect insulin sensitivity remain to be elucidated.

PMID- 10894819
TI  - Increased production of HDL ApoA-I in homozygous familial defective ApoB-100.
AB  - Familial defective apolipoprotein (apo) B-100 (FDB) is a frequent cause of
      hypercholesterolemia. Hypercholesterolemia in homozygous FDB is less severe than
      in homozygotes for familial hypercholesterolemia. Recently, we showed decreased
      low density lipoprotein (LDL) apoB-100 fractional catabolism and decreased
      production of LDL due to an enhanced removal of apoE-containing precursors in a
      patient with homozygous FDB. The effects of defective apoB-100 on high density
      lipoprotein (HDL) metabolism are unknown. We studied HDL apoA-I metabolism in
      this FDB patient and in 6 control subjects by using (2)H(3)-L-leucine as a
      tracer. ApoA-I levels were normal in all study subjects. However, the fractional
      catabolic rate and the production rate of apoA-I were increased, by 79% and 70%,
      respectively, in FDB; the fractional catabolic rate of apoA-I in FDB was 0.34
      day(-1) compared with 0.19+/-0.03 day(-1) in normal controls. The production rate
      of apoA-I in FDB was 18.4 mg. kg(-1). d(-1) compared with 10.8+/-2.3 mg. kg(-1).
      d(-1) in controls. Thus, we have shown for the first time that defective apoB-100
      may influence HDL kinetics. The increase in total HDL turnover might enhance
      reverse cholesterol transport and could contribute to the seemingly benign
      clinical course of FDB compared with that of familial hypercholesterolemia.

PMID- 10894820
TI  - Apolipoprotein E2 (Lys146-->Gln) causes hypertriglyceridemia due to an
      apolipoprotein E variant-specific inhibition of lipolysis of very low density
      lipoproteins-triglycerides.
AB  - The apolipoprotein E2 (Lys146-->Gln) variant is associated with a dominant form
      of familial dysbetalipoproteinemia. Heterozygous carriers of this variant have
      elevated levels of plasma triglycerides, cholesterol, and apolipoprotein E
      (apoE). It was hypothesized that the high amounts of triglycerides in the very
      low density lipoprotein (VLDL) fraction are due to a disturbed lipolysis of VLDL.
      To test this hypothesis, apoE knockout mice were injected with an adenovirus
      containing the human APOE*2 (Lys146-->Gln) gene, Ad-E2(146), under the control of
      the cytomegalovirus promoter. ApoE knockout mice injected with an adenovirus
      vector encoding human apoE3 (Ad-E3) were used as controls. Five days after
      adenovirus injection, plasma cholesterol levels of mice injected with a high dose
      of Ad-E2(146) (2x10(9) plaque-forming units) were not changed compared with
      preinjection levels, whereas in the group who received a low dose of Ad-E2(146)
      (5x10(8) plaque-forming units) and in the groups injected with a low or a high
      dose of Ad-E3, plasma cholesterol levels were decreased 5-, 6-, and 12-fold,
      respectively. Plasma triglycerides were not affected in mice injected with Ad-E3.
      In contrast, a 7-fold increase in plasma triglycerides was observed in mice
      injected with the low dose of Ad-E2(146) compared with mice injected with Ad-E3.
      Injection with the high dose of Ad-E2(146) resulted in a dramatic increase of
      plasma triglycerides (50-fold compared with Ad-E3 injection). In vitro lipolysis
      experiments showed that the lipolysis rate of VLDLs containing normal amounts of
      apoE2 (Lys146-->Gln) was decreased by 54% compared with that of VLDLs containing
      comparable amounts of apoE3. The in vivo VLDL-triglyceride production rate of Ad
      E2(146)-injected mice was not significantly different from that of Ad-E3-injected
      mice. These results demonstrate that expression of apoE2 (Lys146-->Gln) causes
      hypertriglyceridemia due to an apoE variant-specific inhibition of the hydrolysis
      of VLDL-triglycerides.

PMID- 10894821
TI  - Effects of ApoE genotype on ApoB-48 and ApoB-100 kinetics with stable isotopes in
      humans.
AB  - Subjects with the apolipoprotein (apo) E4 allele have been shown to have higher
      low density lipoprotein (LDL) cholesterol and apoB levels than do subjects with
      the other alleles. To elucidate the metabolic mechanisms responsible for this
      finding, we examined the kinetics of apoB-48 within triglyceride-rich
      lipoproteins (TRLs) and of apoB-100 within very low density lipoprotein (VLDL),
      intermediate density lipoprotein (IDL), and LDL by using a primed constant
      infusion of [5,5,5-(2)H(3)]leucine in the fed state (hourly feeding) during
      consumption of an average American diet in 18 normolipidemic subjects, 12 of whom
      had the apoE3/E3 genotype and 6, the apoE3/E4 genotype. Lipoproteins were
      isolated by ultracentrifugation and apolipoproteins, by sodium dodecyl sulfate
      gels; isotope enrichment was assessed by gas chromatography-mass spectrometry.
      Kinetic parameters were calculated by multicompartmental modeling of the data
      with SAAM II software. Compared with the apoE3/E3 subjects, the apoE3/E4 subjects
      had significantly higher levels of total apoB, 100. 1+/-17.8 versus 135.4+/-34.0
      mg/dL (P=0.009), and significantly higher levels of LDL apoB-100, 88.1+/-19.2
      versus 127.5+/-32.7 mg/dL (P=0.005), respectively. The pool size of TRL apoB-48
      was 17.4% lower for apoE3/E4 subjects compared with apoE3/E3 subjects due to a
      33.3% lower production rate (P=0.28). There was no significant difference in the
      TRL apoB-48 fractional catabolic rate (5.1+/-2.2 versus 5.0+/-2.1 pools per day).
      The pool size for VLDL apoB-100 was 36% lower for apoE3/E4 subjects compared with
      apoE3/E3 subjects due entirely to a 30% lower production rate (P=0.04). The LDL
      apoB-100 pool size was 57.8% higher (P=0.003) for apoE3/E4 subjects compared with
      apoE3/E3 subjects due to a 35.5% lower fractional catabolic rate of LDL apoB-100
      (P=0.003), with no significant difference in production rate. In addition, 77% of
      VLDL apoB-100 was converted to LDL apoB-100 in apoE3/E4 subjects compared with
      58% in apoE3/E3 subjects (P=0.05). In conclusion, the presence of 1 E4 allele was
      associated with higher LDL apoB-100 levels owing to lower fractional catabolism
      of LDL apoB-100 and a 33% increase in the conversion of VLDL apoB-100 to LDL apoB
      100.

PMID- 10894822
TI  - MRI cerebral white matter lesions and paraoxonase PON1 polymorphisms : three-year
      follow-up of the austrian stroke prevention study.
AB  - White matter lesions (WMLs) on magnetic resonance imaging (MRI) scans of older
      persons are thought to be caused by cerebral small-vessel disease. As they
      progress, these brain abnormalities frequently result in cognitive decline and
      gait disturbances, and their predictors are incompletely understood. Genetic risk
      factors have been implicated but remain undetermined so far. We examined whether
      2 common polymorphisms of the paraoxonase (PON1) gene leading to a methionine (M
      allele)-leucine (L allele) interchange at position 54 and an arginine (B allele)
      glutamine (A allele) interchange at position 191 are associated with the presence
      and progression of WMLs. We studied 264 community-dwelling subjects without
      neuropsychiatric disease (ages 44 to 75 years). All underwent vascular risk
      factor assessment, brain MRI, and PON1 genotyping. MRI scanning was repeated
      after 3 years. The extent and number of WMLs were recorded by 3 independent
      readers. Progression of WMLs was assessed by direct scan comparison. The final
      rating relied on the majority judgment of the 3 readers. The LL, LM, and MM
      genotypes were noted in 111 (42.0%), 118 (44.7%), and 35 (13.3%) subjects,
      respectively; the AA, AB, and BB genotypes occurred in 146 (55.3%), 98 (37.1%),
      and 20 (7.8%) individuals, respectively. Carriers of the LL genotype showed a
      nonsignificant trend toward more extensive WMLs and more frequently demonstrated
      lesion progression over the 3-year observation period (P=0.03). The polymorphism
      at position 191 had no effect. Logistic regression analysis yielded age (odds
      ratio, 1.08/y), diastolic blood pressure (odds ratio, 1.05/mm Hg), and LL
      paraoxonase genotype (odds ratio, 2. 65) to be significant predictors of WML
      progression. These data suggest that the LL PON1 genotype at position 54
      influences the extent and progression of WMLs in elderly subjects.

PMID- 10894823
TI  - Biphasic effects of the natural estrogen 17beta-estradiol on hepatic cholesterol
      metabolism in intact female rats.
AB  - The protective influence of estrogens in cardiovascular disease is believed to be
      partly due to beneficial effects on cholesterol metabolism. Much of the
      experimental data are based on models in which synthetic estrogens have been used
      in pharmacological doses, and therefore, the physiological role of estrogens in
      cholesterol metabolism is uncertain. To evaluate this important issue, we
      performed experiments in intact female rats with use of the natural estrogen
      17beta-estradiol (E2) administered either subcutaneously or orally. After
      physiological doses of E2 (< or =0.04 mg. kg(-1). d(-1)) were administered,
      plasma levels of high density lipoprotein (HDL) cholesterol and apolipoprotein
      (apo) A-I were increased. In the liver, 3-hydroxy-3-methylglutaryl coenzyme A
      reductase and cholesterol 7alpha-hydroxylase activities were increased, as well
      as cholesterol 7alpha-hydroxylase mRNA levels. These effects were abolished
      during treatment with higher doses of E2, whereas apo A-I mRNA increased in a
      dose-dependent way. After treatment with pharmacological doses of E2 (> or =0.2
      mg. kg(-1). d(-1)), the number of hepatic low density lipoprotein receptors
      increased and plasma cholesterol was reduced. These effects were similar after
      both oral and subcutaneous administration of E2. Our results show that the
      responses to E2 are biphasic: plasma HDL, apo A-I, and hepatic enzyme activities
      governing bile acid and cholesterol synthesis increased only at physiological
      doses of E2. At pharmacological doses of E2, hepatic low density lipoprotein
      receptors are stimulated and plasma cholesterol is reduced. Therefore, under
      physiological conditions, E2 exerts its major effects on hepatic cholesterol
      metabolism through mechanisms other than stimulation of low density lipoprotein
      receptor expression.

PMID- 10894824
TI  - Characterization of signal properties in atherosclerotic plaque components by
      intravascular MRI.
AB  - Magnetic resonance imaging (MRI) is capable of distinguishing between
      atherosclerotic plaque components solely on the basis of biochemical differences.
      However, to date, the majority of plaque characterization has been performed by
      using high-field strength units or special coils, which are not clinically
      applicable. Thus, the purpose of the present study was to evaluate MRI properties
      in histologically verified plaque components in excised human carotid
      endarterectomy specimens with the use of a 5F catheter-based imaging coil,
      standard acquisition software, and a clinical scanner operating at 0.5 T. Human
      carotid endarterectomy specimens from 17 patients were imaged at 37 degrees C by
      use of an opposed solenoid intravascular radiofrequency coil integrated into a 5F
      double-lumen catheter interfaced to a 0.5-T General Electric interventional
      scanner. Cross-sectional intravascular MRI (156x250 microm in-plane resolution)
      that used different imaging parameters permitted the calculation of absolute
      T1and T2, the magnetization transfer contrast ratio, the magnitude of regional
      signal loss associated with an inversion recovery sequence (inversion ratio), and
      regional signal loss in gradient echo (gradient echo-to-spin echo ratio) in
      plaque components. Histological staining included hematoxylin and eosin, Masson's
      trichrome, Kossa, oil red O, and Gomori's iron stain. X-ray micrographs were also
      used to identify regions of calcium. Seven plaque components were evaluated:
      fibrous cap, smooth muscle cells, organizing thrombus, fresh thrombus, lipid,
      edema, and calcium. The magnetization transfer contrast ratio was significantly
      less in the fibrous cap (0.62+/-13) than in all other components (P<0.05) The
      inversion ratio was greater in lipid (0.91+/-0.09) than all other components
      (P<0.05). Calcium was best distinguished by using the gradient echo-to-spin echo
      ratio, which was lower in calcium (0.36+/-0.2) than in all plaque components,
      except for the organizing thrombus (P<0.04). Absolute T1 (range 300+/-140 ms for
      lipid to 630+/-321 ms for calcium) and T2 (range 40+/-12 ms for fresh thrombus to
      59+/-21 ms for smooth muscle cells) were not significantly different between
      groups. In vitro intravascular MRI with catheter-based coils and standard
      software permits sufficient spatial resolution to visualize major plaque
      components. Pulse sequences that take advantage of differences in biochemical
      structure of individual plaque components show quantitative differences in signal
      properties between fibrous cap, lipid, and calcium. Therefore, catheter-based
      imaging coils may have the potential to identify and characterize those
      intraplaque components associated with plaque stability by use of existing whole
      body scanners.

PMID- 10894825
TI  - Hyperlipidemia promotes thrombosis after injury to atherosclerotic vessels in
      apolipoprotein E-deficient mice.
AB  - The increased risk of hyperlipidemia on the development of complications of
      atherosclerosis is well established. Cholesterol-lowering therapies lead to a
      decrease in the incidence of vascular thrombotic events that is out of proportion
      to the reduction in plaque size. This suggests that the occurrence of acute
      thrombosis overlying a disrupted plaque is influenced by changes in lipid levels.
      The influence of acute hyperlipidemia on the development of thrombosis overlying
      an atherosclerotic plaque in vivo has not been extensively studied. We used a
      murine model of vascular injury induced by a photochemical reaction to elicit
      thrombus formation overlying an atherosclerotic plaque. Fifteen apolipoprotein E
      deficient mice were maintained on normal chow until the age of 30 weeks. Five
      days before the induction of thrombosis, 6 mice were started on a high fat diet,
      and 9 mice were continued on normal chow. Mice then underwent photochemical
      injury to the common carotid artery immediately proximal to the carotid
      bifurcation, where an atherosclerotic plaque is consistently present. Mice
      maintained on normal chow developed occlusive thrombi, determined by cessation of
      blood flow, 44+/-5 minutes (mean+/-SEM) after photochemical injury, whereas mice
      fed a high fat chow developed occlusive thrombosis at 27+/-3 minutes (P<0.02).
      Histological analysis confirmed the presence of acute thrombus formation
      overlying an atherosclerotic plaque. These studies demonstrate a useful model for
      assessing the determinants of thrombosis in the setting of atherosclerosis and
      show that acute elevations in plasma cholesterol facilitate thrombus formation at
      sites of atherosclerosis after vascular injury.

PMID- 10894826
TI  - Plasma lipoproteins enhance tissue factor-independent factor VII activation.
AB  - The effect of plasma lipoprotein fractions (large very-low-density lipoprotein,
      small very-low-density lipoprotein, intermediate-density lipoprotein, and low
      density lipoprotein) on initiation of blood coagulation by supporting factor VII
      activation or by stimulating monocytes to express tissue factor was investigated
      in vitro. Endotoxin-free preparations of lipoprotein fractions did not induce
      functional tissue factor in monocytes, whereas all lipoprotein fractions enhanced
      tissue factor-independent activation of factor VII by factor Xa and by factors
      Xa/Va. In contrast, no or only slight enhancement of factor IXa-, factor
      IXa/VIIIa-, factor XIa-, or thrombin-mediated factor VII activation was observed.
      The effect of small very-low-density lipoprotein was less than that of large very
      low-density lipoprotein, and intermediate-density and low-density lipoproteins
      caused an even lower but still significant increase of factor Xa- and factor
      Xa/Va-mediated factor VII activation. When the data were normalized for
      apolipoprotein B-100 content, differences remained between lipoprotein fractions.
      In contrast, when phospholipid content was used for normalization, differences
      between lipoprotein fractions in factor Xa- and factor Xa/Va-mediated factor VII
      activation disappeared, indicating that phospholipids were involved in factor VII
      activation. This was supported by enhancement of factor Xa-mediated factor VII
      activation by synthetic phospholipid vesicles containing negatively charged
      phospholipids.

PMID- 10894827
TI  - Social determinants of von willebrand factor: the Whitehall II study.
AB  - Data from the Whitehall II Study and others have demonstrated a role for the
      metabolic syndrome and fibrinogen underlying the association between social
      position and coronary heart disease. In this study, we examined the role of an
      additional hemostatic factor and marker of endothelial dysfunction, von
      Willebrand factor (vWF). Four thousand five hundred and forty-eight men and 1837
      women were examined in the third phase of the study, which took place between
      1991 and 1993. Employment grade was used as a measure of socioeconomic position.
      An inverse relation between employment grade and vWF was evident (P<0.0003). This
      employment grade gradient was apparent overall, and the relation persisted even
      when nonsmokers and participants with poor health were removed from the analyses
      (P=0.02). The difference between the highest (unified grades 1 to 6) and lowest
      (clerical/support) employment grades in vWF concentrations was 8.9 IU/dL (95% CI
      6.0, 11.8; P<0.001) for men and 6.9 IU/dL (95% CI 4.0, 9.7; P=0.06) for women.
      vWF was associated with a number of biological factors that themselves showed an
      employment grade gradient, including fibrinogen (P<0.001), fasting and postload
      glucose (P<0.05) levels, and fasting and postload insulin (P<0.01) levels.
      Associations with smoking and alcohol intake were apparent. Smoking showed a
      threshold effect, such that only men who smoked >21 cigarettes per day produced a
      significantly increased vWF level (P<0.05) compared with lighter smokers. The
      health-related behaviors explained 25% of the grade gradient in men and 28% in
      women, while the biological factors accounted for 32% in men and 22% in women. We
      conclude that there is a grade gradient in vWF that was not fully explained by
      health-related behaviors and risk factors for coronary heart disease. These data
      are consistent with the hypothesis that endothelial dysfunction is part of the
      explanation for social inequalities in cardiovascular disease.

PMID- 10894828
TI  - Monoclonal antibody designated T2G1 reacts with human fibrin beta-chain but not
      with the corresponding chain from mouse fibrin.

PMID- 10894829
TI  - Toward a checklist for reporting of studies of diagnostic accuracy of medical
      tests.
AB  - BACKGROUND: : "Diagnostic accuracy" refers to the ability of medical tests to
      provide accurate information about diagnosis, prognosis, risk of disease, and
      other clinical issues. Published reports on diagnostic accuracy of medical tests
      frequently fail to adhere to minimal clinical epidemiological standards, and such
      failures lead to overly optimistic assessments of evaluated tests. Our aim was to
      enumerate key items for inclusion in published reports on diagnostic accuracy,
      with a related aim of making the reports more useful for systematic reviews.
      METHODS: : We examined published reports on shortcomings of studies of diagnostic
      accuracy. We prepared an initial draft of a checklist to address common errors
      and presented it at a meeting of editors. After incorporation of comments from
      editors, we published a revised version in Clinical Chemistry in 1997 for comment
      from readers. One of us (E.M.) additionally circulated copies of the draft to
      methodologists and others interested in Evidence-Based Medicine. We updated the
      checklist with input from these sources. RESULTS: : The updated document lists
      items for inclusion in the title, abstract, methods, results, and discussion
      sections of published papers. Depending on the nature of the study, the total
      number of items for a single paper is approximately 40. We invite comments on
      this document, which is freely available at Clinical Chemistry Online, where it
      can accessed readily from the Table of Contents for the July 2000 issue at www.
      clinchem.org/content/vol46/issue7/. Comments (eLetters) can be posted there for
      general reading. CONCLUSIONS: : The suggested revisions incorporated in this
      report appear useful to ensure inclusion of additional information that can allow
      assessment of the validity of the conclusions and the applicability of the study
      in other settings. The list can be useful in formulating guidelines and a
      checklist, which will require testing by authors and study of their effect on
      published studies of diagnostic accuracy.

PMID- 10894830
TI  - Prostate-specific antigen: a cancer fighter and a valuable messenger?
AB  - BACKGROUND: Prostate-specific antigen (PSA) is a valuable prostatic cancer
      biomarker that is now widely used for population screening, diagnosis, and
      monitoring of patients with prostate cancer. Despite the voluminous literature on
      this biomarker, relatively few reports have addressed the issue of its
      physiological function and its connection to the pathogenesis and progression of
      prostate and other cancers. APPROACH: I here review literature dealing with PSA
      physiology and pathobiology and discuss reports that either suggest that PSA is a
      beneficial molecule with tumor suppressor activity or that PSA has deleterious
      effects in prostate, breast, and possibly other cancers. CONTENT: The present
      scientific literature on PSA physiology and pathobiology is confusing. A group of
      reports have suggested that PSA may act as a tumor suppressor, a negative
      regulator of cell growth, and an apoptotic molecule, whereas others suggest that
      PSA may, through its chymotrypsin-like activity, promote tumor progression and
      metastasis. SUMMARY: The physiological function of PSA is still not well
      understood. Because PSA is just one member of the human kallikrein gene family,
      it is possible that its biological functions are related to the activity of other
      related kallikreins. Only when the physiological functions of PSA and other
      kallikreins are elucidated will we be able to explain the currently apparently
      conflicting experimental data.

PMID- 10894831
TI  - Quantitative analysis of aldolase A mRNA in liver discriminates between
      hepatocellular carcinoma and cirrhosis.
AB  - BACKGROUND: Chronic liver diseases can progress to cirrhosis and to
      hepatocellular carcinoma. Timely and unequivocal recognition of the neoplastic
      evolution of cirrhosis is critical. To this aim, we used a noncompetitive reverse
      transcription-PCR procedure to analyze aldolase A mRNA in liver tissue from
      patients with chronic liver diseases at different stages. METHODS: We studied 12
      patients with hepatocellular carcinoma, 19 patients affected by chronic hepatitis
      C or cirrhosis, and 7 healthy controls. Aldolase A mRNA was reverse-transcribed
      to cDNA, which was then amplified by PCR. The amplified segments were "read" with
      a novel dot-blot procedure. A calibrator with the same sequence, synthesized in
      vitro using a T7 phage promoter, was processed at scalar dilutions in parallel to
      the target samples to generate a calibration curve and so quantify the target
      mRNA (detection limit, 0.03 amol; linearity spanning five orders of magnitude).
      RESULTS: Aldolase A mRNA was approximately 10-fold higher in liver biopsies from
      patients with hepatocellular carcinoma vs patients with chronic hepatitis C or
      cirrhosis, and healthy individuals. Furthermore, aldolase A mRNA concentrations
      were 1.2- to 21.3-fold higher in 12 liver biopsies compared with the paired
      surrounding cirrhotic tissue. CONCLUSIONS: The quantitative analysis of liver
      tissue aldolase A mRNA differentiates between nonneoplastic chronic liver
      diseases and hepatocellular carcinoma, which suggests that it has diagnostic
      potential.

PMID- 10894832
TI  - Accurate and rapid "multiplex heteroduplexing" method for genotyping key enzymes
      involved in folate/homocysteine metabolism.
AB  - BACKGROUND: Hyperhomocysteinemia, which is often associated with low folate
      status, is an independent risk factor for cardiovascular diseases and several
      other pathologies. The four most common functional polymorphisms in genes
      involved in folate/homocysteine metabolism are methylenetetrahydrofolate
      reductase (MTHFR) C677T and A1298C, methionine synthase (MS) A2756G, and
      cystathionine beta-synthase (CBS) 844ins68. The pathogenic impact of these
      variants is under active investigation in many laboratories. However,
      conventional genotyping methods, mostly using PCR followed by restriction enzyme
      digestion, often are compromised by partial fragment digestion. There is,
      therefore, a need to develop more reliable approaches to genotyping the above
      polymorphisms that may be applied in large-scale studies. METHODS: Sequence
      specific heteroduplex generators for each of the MTHFR and MS single nucleotide
      polymorphisms were generated by site-directed mutagenesis. These were subcloned
      into a single construct, pHcyHG-1, which could be multiplexed with a simple PCR
      amplification across the CBS 844ins68 polymorphic site to generate composite
      genotype-specific banding patterns from individual genomic DNA samples that could
      be electrophoretically resolved. RESULTS: The "multiplex heteroduplexing" method
      yielded unambiguous MTHFR, MS, and CBS genotypes in a single-tube reaction that
      could be analyzed in a single gel run. CONCLUSIONS: This method permits
      unambiguous genotyping of the four most common functional variants of enzymes
      involved in folate/homocysteine metabolism. It is rapid, reproducible, and
      inexpensive, and requires no special preparative or analytic facilities;
      consequently, it will facilitate large-scale studies of the genetic basis of
      hyperhomocysteinemia and the many pathologies that have been associated with this
      phenotype.

PMID- 10894833
TI  - Manifold-assisted reverse transcription-PCR with real-time detection for
      measurement of the BCR-ABL fusion transcript in chronic myeloid leukemia
      patients.
AB  - BACKGROUND: BCR-ABL fusion mRNA expression in bone marrow or peripheral blood can
      be used as a measure of minimal residual disease in patients with chronic myeloid
      leukemia (CML). METHODS: We used an oligo(dT)-coated manifold support to capture
      the mRNA directly from the cell lysate. After reverse transcription, the cDNA was
      eluted from the manifold support, and BCR-ABL and GAPDH mRNAs were quantified in
      real time using the TaqMan fluorogenic detection system. RESULTS: The detection
      limit of the method was one positive K562 cell among 10(5) negative cells. GAPDH
      was chosen as a reference gene based on the low variation between samples from
      different stages of the disease and the low signal in the absence of reverse
      transcription. The day-to-day variation of the method (CV) was 32%. In 43 blood
      samples from 13 CML patients, mRNA quantification agreed well with cytogenetic
      data. CONCLUSIONS: The proposed procedure constitutes a reproducible and
      sensitive BCR-ABL mRNA quantification method and is suitable to monitor minimal
      residual disease in CML patients.

PMID- 10894834
TI  - Quantitative analysis of tyrosinase transcripts in blood.
AB  - BACKGROUND: Tyrosinase is an enzyme unique to pigment-forming cells. Methods
      using this transcript for detection of melanoma cells in blood have given
      divergent results. Quantitative analytical procedures are therefore needed to
      study the analytical performance of the methods. METHODS: Mononucleated cells
      were isolated by Percoll centrifugation. RNA was isolated by each of three
      methods: Ultraspec(TM)-II RNA isolation system, FastRNA(TM) GREEN Kit, and QIAamp
      RNA Blood Mini Kit. cDNA was synthesized using random hexamer primers. A
      tyrosinase-specific product of 207 bp was amplified by PCR. As an internal
      standard (and competitor) we used a 207-bp cDNA with a base sequence identical to
      the tyrosinase target except for a 20-bp probe-binding region. The PCR products
      were identified by 2, 4-dinitrophenol (DNP)-labeled probes specific for
      tyrosinase (5'DNP-GGGGAGCCTTGGGGTTCTGG-3') and internal standard (5'DNP
      CGGAGCCCCGAAACCACATC-3') and quantified by ELISA. RESULTS: The calibration curves
      were linear and had a broad dynamic measuring range. A detection limit (2 SD
      above zero) of 48 transcripts/mL of blood was obtained from a low control. The
      analytical imprecision was 50% and 48% at concentrations of 1775 and 17 929
      transcripts/mL (n = 12 and 14, respectively). With the cell line SK-Mel 28 added
      to blood and RNA extracted with the Ultraspec, Fast RNA, and QIAamp RNA methods,
      we found (mean +/- SD) 1716+/-1341, 2670+/-3174, and 24 320+/-5332 transcripts/mL
      of blood. Corresponding values were 527+/-497, 2497+/-1033, 14 930+/-1927
      transcripts/mL of blood when the cell line JKM86-4 was added. One high-risk
      patient was followed by repeated analysis of tyrosinase transcripts in blood. The
      melanoma marker 5-S-cysteinyldopa in serum and urine was within reference values,
      but tyrosinase mRNA was slightly increased (120-168 transcripts/mL of blood). The
      tyrosinase mRNA increased to 1860 transcripts/mL concomitant with the increase in
      5-S-cysteinyldopa; later a spleen metastasis was found. CONCLUSIONS: The results
      obtained with different RNA extraction methods illustrate the importance of
      quantitative methods for validation of methods. The use of QIAamp RNA improved
      the extraction efficiency considerably. Data from a case study suggest the assay
      is suitable in the follow-up of patients with high risk of developing metastases.

PMID- 10894835
TI  - Total and pancreatic amylase measured with 2-chloro-4-nitrophenyl-4-O-beta-D
      galactopyranosylmaltoside.
AB  - BACKGROUND: : Many different methods have been used to assay amylase activity,
      using nitrophenylated oligosaccharides as substrate; however, the hydrolysis
      steps in these methods are complex. METHODS: : We developed a new continuously
      monitoring assay for amylase activity in biological fluids, using 2-chloro-4
      nitrophenyl-4-O-beta-D-galactopyranosylmaltoside (GalG2CNP) as the substrate;
      this assay was used with anti-human salivary amylase monoclonal antibodies for
      specific determination of the pancreatic isoenzyme. Amylase converted GalG2CNP
      into beta-D-galactopyranosylmaltose and 2-chloro-4-nitrophenol, which was
      measured at 405 nm. RESULTS: : GalG2CNP was cleaved between 2-chloro-4
      nitrophenol and beta-D-galactopyranosylmaltose and did not undergo transfer
      reactions. The within-assay CVs (n = 20) for total amylase (T-AMY) and pancreatic
      amylase (P-AMY) were 0.6-1.6% and 0.5-2.5%, respectively; and day-to-day CVs (n =
      10) for T-AMY and P-AMY were 0.8-3.7% and 0.6-4.1%, respectively. T-AMY and P-AMY
      activities in serum or urine obtained by the proposed method correlated well with
      those determined by the 2-chloro-4-nitrophenyl 4-O-beta-D-galactopyranosyl-beta
      maltotetraoside method or the modified IFCC method. CONCLUSIONS: : This novel
      assay for T-AMY and P-AMY measures both activities stoichiometrically, directly,
      and easily, and may be suitable for routine procedures.

PMID- 10894836
TI  - Immunoradiometric assay of circulating C-reactive protein: age-related values in
      the adult general population.
AB  - BACKGROUND: : Increased values of C-reactive protein (CRP), the classical acute
      phase protein, within the range below 5 mg/L, previously considered to be within
      the reference interval, are strongly associated with increased risk of
      atherothrombotic events, and are clinically significant in osteoarthritis and
      neonatal infection. METHODS: : A robust new polyclonal-monoclonal solid- phase
      IRMA for CRP was developed, with a range of 0.05-10.0 mg/L. RESULTS: : Plasma CRP
      values in general adult populations from Augsburg, Germany (2291 males and 2203
      females; ages, 25-74 years) and Glasgow, Scotland (604 males and 650 females;
      ages, 25-64 years) were very similar. The median CRP approximately doubled with
      age, from approximately 1 mg/L in the youngest decade to approximately 2 mg/L in
      the oldest, and tended to be higher in females. CONCLUSION: : This extensive data
      set, the largest such study of CRP, provides valuable reference information for
      future clinical and epidemiological investigations.

PMID- 10894837
TI  - Progression criteria for cancer antigen 15.3 and carcinoembryonic antigen in
      metastatic breast cancer compared by computer simulation of marker data.
AB  - BACKGROUND: We investigated the utility of computer simulation models for
      performance comparisons of different tumor marker assessment criteria to define
      progression or nonprogression of metastatic breast cancer. METHODS: Clinically
      relevant values for progressive cancer antigen 15.3 and carcinoembryonic antigen
      concentrations were combined with representative values for background variations
      in a computer simulation model. Fifteen criteria for assessment of longitudinal
      tumor marker data were obtained from the literature and computerized. Altogether,
      7200 different patients, each based on 50 measurements, were simulated. With a
      sampling interval of 4 weeks, the monitoring period for each event was
      approximately 3.8 years. RESULTS: Modulation of the background variation, the
      starting concentrations, and the cutoffs enabled identification of criteria that
      were robust against false-positive signals of progression. CONCLUSIONS: The
      computer simulation model is a fast, effective, and inexpensive approach for
      comparing the diagnostic potential of assessment criteria during clinically
      relevant conditions of steady-state and progressive disease. The model systems
      can be used to generate tumor marker assessment criteria for a variety of
      malignancies and to compare and optimize their diagnostic performance.

PMID- 10894838
TI  - Prevention of in vitro lipolysis by tetrahydrolipstatin.
AB  - BACKGROUND: Metabolic effects of free fatty acids (FFAs) frequently are tested
      using combined infusion of triglycerides and heparin, which stimulates lipolysis
      in vivo. Ongoing in vitro lipolysis, however, probably produces falsely high
      plasma FFA concentrations under these conditions. Therefore, this study aims to
      assess the efficacy of tetrahydrolipstatin (THL) in inhibiting plasma lipolytic
      activity and to improve plasma FFA determination. METHODS: Plasma concentrations
      of FFAs and glycerol were measured in five healthy subjects in the presence and
      absence of THL. Blood was drawn at baseline, during infusion of a triglyceride
      emulsion (1.5 mL/min), and during infusion of triglycerides plus heparin (0.2 IU.
      kg(-1). min(-1)). In addition, the effects of storage temperature of the samples
      were analyzed. RESULTS: In samples frozen immediately after collection, plasma
      FFAs were 28% lower in the presence of THL than in its absence (P = 0.008). When
      THL-free plasma was incubated for 3 h on ice or at room temperature, plasma FFAs
      were 22% (P = 0.02) and 91% (P = 0.0004) higher, respectively, than in samples
      frozen immediately. The addition of THL blunted temperature-dependent in vitro
      lipolysis by 88% (P<0.01) and 89% (P <0.001) after incubation on ice and at room
      temperature, respectively. Changes in plasma glycerol concentrations exhibited
      similar behavior. CONCLUSIONS: THL, which is safe and easy to handle, is a potent
      inhibitor of in vitro lipolysis and could, therefore, be added to blood samples
      drawn during triglyceride/heparin infusions to allow more accurate determination
      of plasma FFA concentrations.

PMID- 10894839
TI  - The costs of disease.
AB  - BACKGROUND: To date there have been no studies identifying and comparing the
      component costs to treat a large number of diseases for hospitalized inpatients.
      METHODS: Hospital costs were analyzed for 486 diagnosis-related groups (DRGs)
      relating to >1.3 million patient discharges from 60 University Hospital members
      of the University HealthSystems Consortium. For each DRG, length of stay, total
      cost, and key cost components were analyzed, including accommodation, intensive
      care, and surgery. RESULTS: In general, total costs of diseases classified as
      surgical exceeded those classified as medical. Diseases involving organ
      transplantation typically cost more than other diseases. However, within the
      studied population, the two DRGs accounting for most total healthcare dollars
      were percutaneous cardiovascular procedures and management of neonates with
      immaturity or respiratory failure. CONCLUSIONS: Considering six key cost
      components, as well as disease complexity and length of stay, the best predictors
      of total costs for medical conditions were the length of stay and accommodation
      (housing, meals, nursing services) costs, whereas for surgical conditions, the
      best predictor of total costs was laboratory costs. This analysis may be used
      within an individual institution to identify surgical or medical diagnoses with
      total or component costs at variance with the group mean. A hospital may focus
      its cost reduction efforts to make decisions to expand, alter, or eliminate
      particular clinical programs based on comparison of its own total and component
      costs with those from other hospitals in the database.

PMID- 10894840
TI  - Laboratory costs in the context of disease.
AB  - BACKGROUND: To determine the contribution of laboratory costs to the overall
      costs of managing hospital patients with different diseases, we studied the costs
      of laboratory testing overall and in relation to the other costs incurred during
      hospitalization. METHODS: We used a database developed by the University
      HealthSystems Consortium containing >1 million patients in 60 University
      Hospitals with diseases included in 486 diagnosis-related groups (DRGs).
      Laboratory costs included in the database comprised those associated with testing
      in the clinical laboratory together with those incurred in point-of-care testing
      and anatomic pathology but not those involving blood products and their
      transfusion. RESULTS: The mean laboratory costs to manage surgical patients were
      greater than those to manage medical patients in 19 of the 25 major diagnostic
      categories. The median laboratory costs for patients with liver transplants
      exceeded $8000, and the laboratory costs to support other organ transplants were
      among the highest. The highest proportion of total costs attributable to the
      laboratory was 18.3% for acute leukemia and kidney and urinary tract signs and
      symptoms, both in children. Laboratory costs were <1.0% of the total costs for
      only 15 DRGs. The highest median daily laboratory cost, $416, was attributable to
      liver transplant patients. Several conditions had median laboratory costs less
      than $30 per day, in spite of lengths of stay that exceeded 10 days in some
      cases. CONCLUSIONS: Although laboratory costs generally average 6% of the total
      costs for surgical conditions and 9% of the total costs for medical conditions,
      there is considerable variability. In general, laboratory costs were relatively
      poorly correlated with total costs. However, observation of high daily laboratory
      costs for many DRGs suggests that reducing length of stay would reduce both
      laboratory and total costs.

PMID- 10894841
TI  - Identification of lignans as major components in the phenolic fraction of olive
      oil.
AB  - BACKGROUND: Because olive oil is an important component of the Mediterranean
      diet, it is necessary to establish unequivocal identification of the major
      potential antioxidant phenolic compounds it contains. METHODS: The major phenolic
      antioxidants in extra virgin olive oil were isolated and purified. Structural
      analysis was conducted using several spectroscopic techniques, including mass
      spectrometry and nuclear magnetic resonance (NMR). In particular, detailed (1)H
      and (13)C NMR data are presented, and several assignment errors in the literature
      are corrected. RESULTS: The data show for the first time that the lignans (+)-1
      acetoxypinoresinol and (+)-pinoresinol are major components of the phenolic
      fraction of olive oils. These lignans, which are potent antioxidants, are absent
      in seed oils and virtually absent in refined virgin oils but are present at
      concentrations of up to 100 mg/kg (mean +/- SE, 41.53+/-3.93 mg/kg; range, 0.65
      99.97 mg/kg) in extra virgin oils. As with the simple phenols and secoiridoids,
      there is considerable interoil variation in lignan concentrations. Foods
      containing high amounts of lignan precursors have been found to be protective
      against breast, colon, and prostate cancer. CONCLUSION: Lignans, as natural
      components of the diet, may be important modulators of cancer chemopreventive
      activity.

PMID- 10894842
TI  - Influence of hemolysis on the measurement of S-100beta protein and neuron
      specific enolase plasma concentrations during coronary artery bypass grafting.

PMID- 10894843
TI  - Rapid measurement of cardiac markers on Stratus CS.

PMID- 10894844
TI  - Validation and comparison of two solid-phase immunoassays for the quantification
      of S-100B in human blood.

PMID- 10894845
TI  - Multiplexed genotyping of beta-globin variants from PCR-amplified newborn blood
      spot DNA by hybridization with allele-specific oligodeoxynucleotides coupled to
      an array of fluorescent microspheres.

PMID- 10894846
TI  - S100B protein concentrations in cord blood: correlations with gestational age in
      term and preterm deliveries.

PMID- 10894847
TI  - Genotyping of HLA-B27 by real-time PCR without hybridization probes.

PMID- 10894848
TI  - Glutathione and glutathione metabolites in small tissue samples and mucosal
      biopsies.

PMID- 10894849
TI  - Enzyme-based diagnosis of classical late infantile neuronal ceroid
      lipofuscinosis: comparison of tripeptidyl peptidase I and pepstatin-insensitive
      protease assays.

PMID- 10894850
TI  - History of clinical chemistry in a children's hospital (1914-1964).
AB  - The historical development of a charitable children's hospital and the evolution
      of its clinical laboratory are presented. With the appearance of practical
      quantitative blood chemistry tests in the period between the two World Wars,
      applications to pediatrics were hampered by the need for ultramicro procedures
      then unavailable and for improved skin-puncture blood sampling. World War II
      brought economic demands that forced the hospital to privatize its beds and to
      charge fee-for-services. In turn, this brought added income, allowing the hiring
      or subsidizing of a professional staff, including the clinical chemist. The
      development of ultramicro blood chemistry followed, along with improved skin
      puncture technology.

PMID- 10894851
TI  - False-positive plasma troponin I with the AxSYM analyzer.

PMID- 10894852
TI  - Thyroid function during pregnancy.

PMID- 10894853
TI  - Thyroid function during pregnancy.

PMID- 10894854
TI  - Capacity and efficiency testing of new immunoassay analyzers.

PMID- 10894855
TI  - Enhanced time-saving extraction procedure for the analysis of fecal fat by
      Fourier transform infrared spectroscopy.

PMID- 10894856
TI  - Serum and plasma samples for ACS:systems cardiac markers.

PMID- 10894857
TI  - Measurement of total protein is not a useful inclusion in liver function test
      profiles.

PMID- 10894858
TI  - High and higher sensitivity CRP.

PMID- 10894859
TI  - Filter paper-collected blood lead testing in children.

PMID- 10894860
TI  - More on filter paper lead testing.

PMID- 10894861
TI  - Compiled by david E. Bruns, editor (dbruns@aacc.org)

PMID- 10894862
TI  - The treatment of advanced gastric cancer: in search of the right combination.

PMID- 10894863
TI  - Final results of a randomized phase III trial of sequential high-dose
      methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and
      fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric
      cancer: A trial of the European Organization for Research and Treatment of Cancer
      Gastrointestinal Tract Cancer Cooperative Group.
AB  - PURPOSE: To compare the efficacy and tolerability of etoposide, leucovorin, and
      bolus fluorouracil (ELF) or infusional fluorouracil plus cisplatin (FUP) with
      that of the reference protocol of fluorouracil, doxorubicin, and methotrexate
      (FAMTX) in advanced gastric cancer. PATIENTS AND METHODS: A total of 399 patients
      with advanced adenocarcinoma of the stomach were randomized and analyzed for
      toxicity, tumor response, and progression-free and overall survival. Only
      reviewed and confirmed responses were considered. The analysis of remission was
      based on assessable patients with documented measurable lesions. The intent-to
      treat principle, log-rank test, and Cox regression model were used for the
      statistical analysis of time-to-event end points. RESULTS: The overall response
      rate for 245 eligible patients with measurable disease was 9% with ELF, 20% with
      FUP, and 12% with FAMTX, with no significant differences. One hundred twelve
      patients were eligible for efficacy in assessable, nonmeasurable disease. No
      change was observed in 66% of patients treated with ELF, 56% with FUP, and 55%
      with FAMTX. Two patients achieved a complete tumor regression (one each for ELF
      and FAMTX). With a median follow-up time of 4.5 years, the median survival times
      were 7.2 months with ELF, 7.2 months with FUP, and 6.7 months with FAMTX,
      respectively, with no significant differences. Nonhematologic and hematologic
      toxicities of ELF, FUP, and FAMTX were acceptable, with neutropenia being the
      major toxicity for all three regimens. Seven treatment-related deaths occurred
      (two with FUP and five with FAMTX). CONCLUSION: All three investigated regimens
      demonstrate modest clinical efficacy and should not be regarded as standard
      treatment for advanced gastric cancer. New strategies should be considered to
      achieve a better clinical efficacy in the treatment of advanced gastric cancer.

PMID- 10894864
TI  - Gemcitabine and cisplatin as induction regimen for patients with biopsy-proven
      stage IIIA N2 non-small-cell lung cancer: a phase II study of the European
      Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group
      (EORTC 08955).
AB  - PURPOSE: Our objective was to better define the activity/feasibility of
      gemcitabine/cisplatin (GC) as induction chemotherapy in patients with stage IIIA
      N2 non-small-cell lung cancer (NSCLC) followed by surgery or radiotherapy within
      a large, ongoing comparative study (EORTC 08941). PATIENTS AND METHODS: Forty
      seven chemotherapy-naive patients with NSCLC, median age of 58 years, stage IIIA
      N2 disease, World Health Organization performance status of 0 or 1, and the
      ability to tolerate a pneumonectomy received gemcitabine 1,000 mg/m(2) on days 1,
      8, and 15 and cisplatin 100 mg/m(2) on day 2, every 4 weeks. Patients received
      induction chemotherapy (three cycles) before re-evaluation and randomization to
      surgery or radiotherapy. RESULTS: Grade 3/4 thrombocytopenia, the main
      hematologic toxicity, occurred in 60% of patients but was not associated with
      bleeding. Full-dose gemcitabine was given in 48% of the courses. Severe
      nonhematologic toxicity was uncommon. Two patients with preexisting, autoimmune
      pulmonary fibrosis had deterioration of pulmonary function after radiotherapy.
      Thirty-three (70.2%; 95% confidence interval, 55.1% to 82.7%) of the 47 eligible
      patients had objective responses (three complete responses and 30 partial
      responses). Mediastinal nodes were tumor-free after induction therapy in 53% of
      cases. Resections were considered complete in 71% of the patients who underwent
      thoracotomy after induction therapy. Median survival for all recruited patients
      (N = 53) was 18.9 months, with an estimated 1-year survival rate of 69%.
      CONCLUSION: In patients with N2 stage IIIA NSCLC, GC is a highly active and well
      tolerated induction regimen. GC should be explored in combination with surgery or
      radiotherapy in stage I and II patients.

PMID- 10894865
TI  - Randomized comparison of cisplatin/vincristine/fluorouracil and
      cisplatin/continuous infusion doxorubicin for treatment of pediatric
      hepatoblastoma: A report from the Children's Cancer Group and the Pediatric
      Oncology Group.
AB  - PURPOSE: Previous studies demonstrated that chemotherapy with either cisplatin,
      vincristine, and fluorouracil (regimen A) or cisplatin and continuous infusion
      doxorubicin (regimen B) improved survival in children with hepatoblastoma. The
      current trial is a randomized comparison of these two regimens. PATIENTS AND
      METHODS: Patients (N = 182) were enrolled onto study between August 1989 and
      December 1992. After initial surgery, patients with stage I-unfavorable histology
      (UH; n = 43), stage II (n = 7), stage III (n = 83), and stage IV (n = 40)
      hepatoblastoma were randomized to receive regimen A (n = 92) or regimen B (n =
      81). Patients with stage I-favorable histology (FH; n = 9) were treated with four
      cycles of doxorubicin alone. RESULTS: There were no events among patients with
      stage I-FH disease. Five-year event-free survival (EFS) estimates were 57% (SD =
      5%) and 69% (SD = 5%) for patients on regimens A and B, respectively (P =.09)
      with a relative risk of 1.54 (95% confidence interval, 0.93 to 2.5) for regimen A
      versus B. Toxicities were more frequent on regimen B. Patients with stage I-UH,
      stage II, stage III, or stage IV disease had 5-year EFS estimates of 91% (SD =
      4%), 100%, 64% (SD = 5%), and 25% (SD = 7%), respectively. Outcome was similar
      for either regimen within disease stages. At postinduction surgery I, patients
      with stage III or IV disease who were found to be tumor-free had no events; those
      who had complete resections achieved a 5-year EFS of 83% (SD = 6%); other
      patients with stage III or IV disease had worse outcome. CONCLUSION: Treatment
      outcome was not significantly different between regimen A and regimen B.
      Excellent outcome was achieved for patients with stage I-UH and stage II
      hepatoblastoma and for subsets of patients with stage III disease. New treatment
      strategies are needed for the majority of patients with advanced-stage
      hepatoblastoma.

PMID- 10894866
TI  - Randomized phase III study comparing conventional-dose doxorubicin plus
      ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human
      granulocyte-macrophage colony-stimulating factor in advanced soft tissue
      sarcomas: A trial of the European Organization for Research and Treatment of
      Cancer/Soft Tissue and Bone Sarcoma Group.
AB  - PURPOSE: This randomized multicenter study was designed to compare the activity
      of a high-dose doxorubicin-containing chemotherapy regimen with a conventional
      standard-dose regimen in adult patients with advanced soft tissue sarcomas
      (ASTS). PATIENTS AND METHODS: Between 1992 and 1995, 314 patients were randomized
      to receive a standard-dose regimen (arm A), containing doxorubicin (50 mg/m(2) on
      day 1) and ifosfamide (5 g/m(2) on day 1), or an intensified regimen (arm B),
      combining doxorubicin (75 mg/m(2) on day 1), the same ifosfamide dose, and
      recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF;
      sargramostim, 250 microgram/m(2) on days 3 to 16); all courses were repeated
      every 3 weeks. RESULTS: The median age of the 294 eligible patients was 50 years.
      They received a median of five chemotherapy cycles. The median dose and relative
      doxorubicin dose-intensity achieved were 245 mg and 97% in arm A and 360 mg and
      99% in arm B, respectively. Thirty-eight percent and 23% of patients presented
      with leiomyosarcomas and liver metastases, respectively. Objective responses were
      observed in 31 (21%) of 147 assessable patients in arm A and in 31 (23.3%) of 133
      in arm B (P =.65). No change was observed in 41.6% and 46.2% of patients in arm A
      and B, respectively. Progression-free survival (PFS) was significantly longer in
      the intensive arm (P =.03). The median duration of the time to progression was 19
      weeks in the conventional arm and 29 weeks in the intensified arm. There was no
      difference in overall survival (P =.98) between the two therapeutic arms.
      Toxicities were manageable in both arms. A grade 3/4 neutropenia and infection
      occurred in 92% and 4.6% of patients in arm A, respectively, and in 90% and 16.6%
      in arm B, respectively. Grade 3/4 thrombocytopenia was more frequent in arm B.
      CONCLUSION: The use of rhGM-CSF allowed safe escalation of chemotherapy doses.
      Despite a 50% increase of the doxorubicin dose-intensity, the high-dose regimen
      failed to demonstrate any impact on survival in patients with ASTS. The low
      complete response rate, the high incidence of leiomyosarcomas, and liver
      metastases may in part explain these results. However, the lengthening of the PFS
      in the intensive arm, because of the quality of stable disease and inappropriate
      tumor evaluation policies that potentially lead to an underestimation of
      antitumor activity, does not definitively refute the use of a high-dose
      chemotherapy regimen in selected patients with ASTS.

PMID- 10894867
TI  - MDR1 gene expression and outcome in osteosarcoma: a prospective, multicenter
      study.
AB  - PURPOSE: Increased expression of the multidrug resistance gene (MDR1) has been
      implicated in osteosarcoma prognosis. This study represents the first prospective
      assessment of the prognostic value of MDR1 mRNA expression in patients with newly
      diagnosed extremity osteosarcoma. PATIENTS AND METHODS: A series of patients with
      high-grade, nonmetastatic extremity osteosarcoma were enrolled from six tertiary
      care institutions and observed prospectively for tumor recurrence (median follow
      up duration, 30 months). All patients were treated with (neo)adjuvant
      chemotherapy and surgery. Tumors from 123 patients were analyzed for MDR1 mRNA
      expression. The association of the level of MDR1 expression with the risk of
      systemic recurrence was examined using survival analyses with traditional and
      histologic markers as prognostic factors. RESULTS: Using the highest MDR1 value
      for each patient, a dose-response relationship was not identified between the
      level of MDR1 expression and systemic relapse (relative risk, 1.15; P =.44).
      Analyses based on biopsy or resection values alone gave similar results (P =.11
      and.41, respectively, log rank test). In multivariate analysis, large tumor size
      (> 9 cm) was the only significant independent predictor of systemic outcome
      (relative risk, 2.8; P =.002). CONCLUSION: We did not identify any correlation
      between MDR1 mRNA expression and disease progression in patients with
      osteosarcoma. It is likely that alterations in other genes are involved in
      resistance to chemotherapy in osteosarcoma and that they play a more critical
      role than MDR1 in this disease.

PMID- 10894868
TI  - Cognitive function in breast cancer patients receiving adjuvant chemotherapy.
AB  - PURPOSE: Breast cancer patients receiving chemotherapy have complained of
      difficulties in their ability to remember, think, and concentrate. This study
      assessed whether there are differences in cognitive function between breast
      cancer patients treated with standard-dose adjuvant chemotherapy compared with
      healthy controls. PATIENTS AND METHODS: The High Sensitivity Cognitive Screen and
      the Profile of Mood States (POMS) were used to assess cognitive function and mood
      in a group of 107 women. The women consisted of 31 breast cancer patients
      receiving adjuvant chemotherapy (group A), 40 breast cancer patients who had
      completed adjuvant chemotherapy a median of 2 years earlier (group B), and 36
      healthy controls (group C). RESULTS: Univariate analysis showed statistically
      significant differences (P =.009) in overall cognitive function scores between
      groups A and C, with poorer function in patients receiving adjuvant chemotherapy.
      These differences remained significant (P =.046) when controlling for age,
      education level, and menopausal status. More patients had moderate or severe
      cognitive impairment in groups A and B than in controls (P </=.002). There were
      no significant differences in POMS scores between the groups, suggesting that the
      differences seen in cognitive scores were unlikely to be because of mood
      disturbance. CONCLUSION: Cognitive differences were observed in breast cancer
      patients receiving adjuvant chemotherapy compared with healthy controls. These
      differences did not seem to be caused by significant differences in mood
      disturbance between the two groups. If confirmed, these results have substantial
      implications for informed consent, counseling, and psychosocial support of
      patients receiving adjuvant chemotherapy for breast cancer.

PMID- 10894869
TI  - Time-dependent relevance of steroid receptors in breast cancer.
AB  - PURPOSE: To analyze the time-dependent prognostic role of the investigated
      variables, considered, when appropriate, on a continuous scale, for the purpose
      of evaluating and describing the interrelationships between clinically relevant
      patient and tumor characteristics (age, size and histology, and estrogen receptor
      [ER] and progesterone receptor content) and the risk of new disease
      manifestation. PATIENTS AND METHODS: We applied a flexible statistical model to a
      case series of 1,793 patients with axillary lymph node-negative breast cancer
      with a minimal potential follow-up of 10 years. To avoid a potential confounding
      effect of adjuvant treatment, only patients given local-regional therapy until
      relapse were considered. RESULTS: ER content and tumor size (adjusted for all the
      other covariates) showed a time-dependent relationship with the risk of new
      disease manifestations. In particular, ER content failed to show a prognostic
      effect within the first years of follow-up; thereafter, a positive association
      with risk of relapse was observed. For tumor size, within the first years of
      follow-up, the risk of relapse was directly related to size for only tumors up to
      2.5 cm in diameter; thereafter, the impact on prognosis progressively decreased.
      CONCLUSION: The availability of a long follow-up on a large breast cancer series,
      as well as the use of innovative statistical approaches, allowed us to explore
      the functional relation between steroid receptors and clinical outcome and to
      generate a hypothesis on the involvement of ER in favoring long-term metastasis
      development.

PMID- 10894870
TI  - Phase II evaluation of thalidomide in patients with metastatic breast cancer.
AB  - PURPOSE: To determine the efficacy, safety, pharmacokinetics, and effect on serum
      angiogenic growth factors of two dose levels of thalidomide in patients with
      metastatic breast cancer. PATIENTS AND METHODS: Twenty-eight patients with
      progressive metastatic breast cancer were randomized to receive either daily 200
      mg of thalidomide or 800 mg to be escalated to 1,200 mg. Fourteen heavily
      pretreated patients were assigned to each dose level. Each cycle consisted of 8
      weeks of treatment. Pharmacokinetics and growth factor serum levels were
      evaluated. RESULTS: No patient had a true partial or complete response. On the
      800-mg arm, 13 patients had progressive disease at or before 8 weeks of treatment
      and one refused to continue treatment. The dose was reduced because of somnolence
      to 600 mg for five patients and to 400 mg for two and was increased for one to
      1,000 mg and for four to 1,200 mg. On the 200-mg arm, 12 patients had progressive
      disease at or before 8 weeks and two had stable disease at 8 weeks, of whom one
      was removed from study at week 11 because of grade 3 neuropathy and the other had
      progressive disease at week 16. Dose-limiting toxicities included somnolence and
      neuropathy. Adverse events that did not require dose or schedule modifications
      included constipation, fatigue, dry mouth, dizziness, nausea, anorexia,
      arrhythmia, headaches, skin rash, hypotension, and neutropenia. Evaluation of
      circulating angiogenic factors and pharmacokinetic studies failed to provide
      insight into the reason for the lack of efficacy. CONCLUSION: Single-agent
      thalidomide has little or no activity in patients with heavily pretreated breast
      cancer. Further studies that include different patient populations and/or
      combinations with other agents might be performed at the lower dose levels.

PMID- 10894871
TI  - Cyclophosphamide, methotrexate, and fluorouracil versus tamoxifen plus ovarian
      suppression as adjuvant treatment of estrogen receptor-positive pre
      /perimenopausal breast cancer patients: results of the Italian Breast Cancer
      Adjuvant Study Group 02 randomized trial. boccardo@hp380.ist.unige.it.
AB  - PURPOSE: To compare the efficacy of chemotherapy versus that of tamoxifen plus
      ovarian suppression in pre-/perimenopausal estrogen receptor-positive patients
      with early breast cancer. PATIENTS AND METHODS: Patients were randomly assigned
      to receive either six cycles of a standard regimen of cyclophosphamide 100
      mg/m(2) orally days 1 to 14, methotrexate 40 mg/m(2) intravenously (IV) days 1
      and 8, and fluorouracil 600 mg/m(2) IV days 1 and 8 (CMF), with all drugs
      restarted on day 29, or 5 years of tamoxifen, 30 mg/d, plus ovarian suppression
      with surgical oophorectomy, ovarian irradiation, or monthly goserelin 3.6-mg
      injections. Disease-free survival was the main study end point. Overall survival
      and toxicity were additional end points. RESULTS: Between 1989 and 1997, 120
      patients were assigned to CMF and 124 to tamoxifen and ovarian suppression
      (oophorectomy, n = 6; ovarian irradiation, n = 31; and goserelin injections, n =
      87). At the time of analysis (median follow-up time, 76 months; range, 9 to 121
      months), 82 patients had relapsed and 39 had died. No difference between groups
      had emerged with respect to either disease-free or overall survival. Treatments
      were comparable even in respect to age, tumor size, and nodal status, although a
      nonsignificant trend favored patients with poorly differentiated tumors treated
      with CMF. Leukopenia, nausea, vomiting, stomatitis, and alopecia were
      significantly more common in patients treated with CMF. There were few patients
      who developed benign gynecologic changes in either group, and numbers were
      comparable. CONCLUSION: The combination of tamoxifen with ovarian suppression
      seems to be safe and to yield comparable results relative to standard CMF.

PMID- 10894872
TI  - Occult ovarian tumors in women with BRCA1 or BRCA2 mutations undergoing
      prophylactic oophorectomy.
AB  - PURPOSE: To review the findings at prophylactic oophorectomy of a series of women
      who presented to a familial breast and ovarian cancer clinic. MATERIALS AND
      METHODS: Data from medical charts, operative notes, and pathology reports were
      collected on women who had undergone prophylactic oophorectomies because of the
      elevated risk of ovarian cancer. Because only a subset of patients underwent
      BRCA1 and BRCA2 testing, each patient's risk of hereditary predisposition was
      calculated using the Berry-Parmigiani model and family history data. RESULTS:
      From June 1989 to December 1998, 50 women seen at our clinic underwent
      prophylactic oophorectomy, 33 of whom had a calculated risk of carrying a
      germline BRCA1 or BRCA2 mutation greater than 25%. Among this group, four
      incidental tumors were found (four of 33, or 12%); one tumor was noted at the
      time of surgery and three were noted only in the final pathology. Two patients
      had microscopic, poorly differentiated serous adenocarcinomas in multiple sites
      on both ovaries. A third patient had a bilateral serous borderline tumor with
      micropapillary features. The fourth patient had a microscopic serous borderline
      ovarian tumor. All four patients had germline BRCA1 or BRCA2 mutations, and three
      had unremarkable transvaginal ultrasonography examinations within 6 months before
      prophylactic surgery. CONCLUSION: Foci of malignant tumor are not uncommon in
      prophylactic oophorectomies performed in women at very high risk for ovarian
      cancer and may not be detected on ultrasonograms. Surgeons should have a high
      suspicion of finding cancer in these women at the time of prophylactic surgery,
      and careful pathologic assessment of the specimens should be conducted.

PMID- 10894873
TI  - Docetaxel for patients with paclitaxel-resistant Mullerian carcinoma.
AB  - PURPOSE: To determine the efficacy and toxicity of docetaxel in patients with
      mullerian carcinoma resistant to paclitaxel. PATIENTS AND METHODS: Thirty-two
      patients with epithelial ovarian cancer, fallopian tube cancer, or primary
      peritoneal cancer who failed paclitaxel-based chemotherapy received either 100 or
      75 mg/m(2) of docetaxel every 3 weeks. Resistance to paclitaxel was defined as
      either progression of disease during treatment, failure to achieve regression of
      disease after at least four courses, or rapid recurrence (within 6 months) after
      completion of therapy. RESULTS: Eighteen patients were treated on a formal
      protocol and fourteen with the commercially available docetaxel. Thirty were
      assessable for response. Toxicities were thoroughly evaluated in the 18 patients
      on protocol. Twenty-seven patients (85%) had epithelial ovarian cancer. The
      overall response rate was 23% (one complete and six partial responses), with a
      median survival time of 44 weeks (9.5 months). Nine patients had stable disease
      and 14 progressive disease. Among 19 patients who progressed during prior
      paclitaxel treatment, two (11%) responded to docetaxel, compared with five (45%)
      of 11 patients in other paclitaxel-resistance categories. The responders had a
      median taxane-free interval (ie, the time between the last paclitaxel and first
      docetaxel treatment) of 73 weeks, compared with 19 weeks for the nonresponder
      group. Toxic effects were as expected. CONCLUSION: Docetaxel is an active
      chemotherapeutic agent in patients with mullerian carcinoma previously treated
      with paclitaxel-based chemotherapy, especially in the patients who had a long
      taxane-free interval after a previous short response to paclitaxel.

PMID- 10894874
TI  - Survival advantage from higher-dose radiation therapy for clinically localized
      prostate cancer treated on the Radiation Therapy Oncology Group trials.
AB  - PURPOSE: We evaluated the effect of external-beam radiation therapy on disease
      specific survival (death from causes related to prostate cancer) and overall
      survival in men with clinically localized prostate cancer. METHODS: From 1975 to
      1992, 1,465 men with clinically localized prostate cancer received radiation
      therapy on four Radiation Therapy Oncology Group phase III randomized trials and
      were pooled for this analysis. No one received androgen-deprivation therapy with
      his initial treatment. All original histology had central pathologic review for
      grading using the Gleason classification system. Total delivered radiation dose
      ranged from 60 to 78 Gy (median, 68.4 Gy). The median follow-up time was 8 years.
      RESULTS: A Cox regression model revealed that Gleason score was an independent
      predictor of disease-specific survival and overall survival. The 10-year disease
      specific survival rates by Gleason score were as follows: score of 2 through 5,
      85%; score of 6, 79%; score of 7, 62%; and score of 8 through 10, 43%.
      Stratifying outcome by this important prognostic factor revealed that higher
      radiation dose was a significant predictor for improved disease-specific survival
      and overall survival only for those patients whose cancers had Gleason scores of
      8 through 10 (P <.05). After adjusting for clinical T stage, nodal status, and
      age, treating with a higher radiation dose was associated with a 29% lower
      relative risk of death from prostate cancer and 27% reduced mortality rate (P
      <.05). CONCLUSION: These data demonstrate that higher-dose radiation therapy can
      significantly reduce the risk of dying from prostate cancer in men with
      clinically localized disease. This survival benefit is restricted to men with
      poorly differentiated cancers.

PMID- 10894875
TI  - Quantitative bone single-photon emission computed tomography for prediction of
      pain relief in metastatic bone disease treated with rhenium-186 etidronate.
AB  - PURPOSE: To calculate radiation doses of rhenium-186 ((186)Re) etidronate in
      painful bone metastases using quantitative bone single-photon emission computed
      tomography (SPECT) and to determine the threshold dose for predicting pain
      relief. We also wanted to determine whether technetium-99m ((99m)Tc) methylene
      diphosphonate (MDP) concentrations predict radiation doses of (186)Re etidronate
      in painful lesions. MATERIALS AND METHODS: Forty-eight patients with breast and
      prostate cancer were evaluated. Patients received therapeutic doses of (186)Re
      etidronate. The area under the pain over time curve (AUPC) was measured for 8
      weeks after treatment. Response was calculated as the percentage of change in
      AUPC. Quantitative bone SPECT (QBS)-measured concentration of (186)Re etidronate
      was used for calculating radiation doses. Receiver operating characteristics
      curve analysis determined the radiation dose threshold that best separated
      responders from nonresponders. SPECT-measured concentration of (186)Re etidronate
      in the urinary bladder was correlated with its concentration in the voided urine.
      Concentration of (99m)Tc MDP was compared with radiation doses to painful
      metastases. RESULTS: The radiation dose threshold was 2.10 Gy. For a decrease of
      50% in the AUPC, the positive predictive value (PPV) of this value was 75% and
      the negative predictive value (NPV) was 88%. For a decrease in pain of 33%, the
      PPV was 84% and the NPV was 81%. In prostate cancer patients only, the PPV was
      81% and the NPV was 92%. The correlation between in vivo/in vitro measured urine
      concentration was 0.90. The correlation between (99m)Tc MDP concentration and
      radiation doses of (186)Re etidronate was 0.92. CONCLUSION: QBS-measured
      radiation doses of (186)Re etidronate in painful metastases are a good predictor
      of pain relief. Bone SPECT using (99m)Tc MDP predicts radiation doses delivered
      by (186)Re etidronate.

PMID- 10894876
TI  - Cost of outpatient blood transfusion in cancer patients.
AB  - PURPOSE: To determine the cost of outpatient RBC transfusion from the provider's
      perspective at a major urban, academic cancer center. PATIENTS AND METHODS: We
      retrospectively studied 517 cancer patients with hematologic or solid tumors who
      received blood during fiscal year 1995 to 1996. A process-flow diagram was
      developed, and cost and utilization data for 12 months were collected and
      analyzed. A structured interview process was used to identify all direct and
      indirect costs from within the inpatient unit, blood bank, and outpatient clinic.
      Average costs were computed for the entire sample and for specific subgroups.
      RESULTS: In 1998 dollars, the average cost per RBC unit was $469 for adults and
      $568 for pediatric cancer patients. Adults and children generally received two
      and one RBC units per transfusion, respectively. Therefore, the average cost of a
      two-unit transfusion was $938 for adults. Patients with hematologic tumors
      required more RBC units (7.1 RBC units per year) at a higher average cost ($512
      per RBC unit) than patients with solid tumors (4.7 RBC units per year, $474 per
      RBC unit). Further variations across tumor types were observed. Overhead, direct
      material, and direct labor represented 46%, 19%, and 35% of total costs
      respectively. CONCLUSION: The cost of outpatient RBC transfusions in cancer
      patients is higher than previously reported, in part because overhead costs and
      fixed costs might have been underestimated in previous studies. Furthermore, age,
      tumor type, and geographic variations in the cost of fixed assets and labor have
      a substantial impact on the cost of blood. The results indicate that the cost
      effectiveness of alternatives to transfusions in the management of cancer
      patients may have been underestimated in the existing literature.

PMID- 10894877
TI  - Mobilization of peripheral-blood stem cells by concurrent administration of
      daniplestim and granulocyte colony-stimulating factor in patients with breast
      cancer or lymphoma.
AB  - PURPOSE: To evaluate the safety and hematopoietic activity of daniplestim
      administered concurrently with granulocyte colony-stimulating factor (G-CSF) for
      peripheral-blood stem-cell (PBSC) mobilization. PATIENTS AND METHODS: In the
      initial dose-escalation phase, 25 patients with adenocarcinoma of the breast (AB;
      13 patients) or lymphoma (12 patients) were given daniplestim at doses ranging
      from 0.1 to 3.75 microgram/kg/d plus G-CSF 10 microgram/kg/d. In the randomized
      phase, 52 patients with AB (27 patients) or lymphoma (25 patients) were
      randomized within disease categories to the daniplestim dose chosen in the dose
      escalation phase plus G-CSF 10 microgram/kg/d (D+G) or placebo plus G-CSF 10
      microgram/kg/d (P+G) for up to 7 days. RESULTS: A daniplestim dose of 2. 5
      microg/kg/d was chosen for further study because it was hematopoietically active
      and had an acceptable side-effect profile. In the randomized phase, in patients
      with AB, D+G was associated with a higher probability (P =.0696) of collecting
      >/= 2.5 x 10(6) CD34(+) cells/kg and significantly higher circulating CD34(+)
      cell counts (P =.0498) on days 6 through 9 after the initiation of dosing. The
      target level was more likely to be reached with additional leukaphereses in the
      patients given D+G. Patients given P+G did not benefit from additional
      leukaphereses beyond the first procedure. The type of mobilization did show a
      trend toward a shorter duration of neutropenia in the D+G group. The adverse
      events with D+G consisted largely of mild to moderate flu-like symptoms,
      including headache and fever, and occurred more frequently than with P+G.
      CONCLUSION: Daniplestim administered at 2.5 microgram/kg/d is tolerable and
      active when combined with G-CSF, and the combination may prove more effective
      than G-CSF alone in promoting the collection of adequate numbers of CD34(+) cells
      for PBSC infusion in patients with AB.

PMID- 10894878
TI  - Phase I clinical and pharmacokinetic study of oral S-1 in patients with advanced
      solid tumors.
AB  - PURPOSE: To investigate the side effects, determine the maximum-tolerated dose
      (MTD), and study the pharmacokinetics of S-1, an oral fluoropyrimidine-based
      antineoplastic agent consisting of the fluorouracil (5-FU) prodrug tegafur
      combined with two modulators, 5-chloro-2,4-dihydroxypyridine and potassium
      oxonate. PATIENTS AND METHODS: Patients with advanced solid tumors received S-1
      bid for 28 days, followed by 1 week of rest. 5-FU pharmacokinetics were
      investigated after a single initial dose of S-1 during the first 24 hours and
      weekly thereafter. RESULTS: Twenty-eight patients received S-1 at the four
      consecutive dose levels of 25, 45, 35, and 40 mg/m(2). The MTD was initially
      found at 45 mg/m(2), with diarrhea as the dose-limiting toxicity (DLT). Diarrhea
      was also the DLT at the dose of 40 mg/m(2), which was the MTD for patients
      exposed to extensive prior chemotherapy. Other toxicities were generally mild.
      Two patients had a reduction of more than 50% in tumor dimension. Plasma
      pharmacokinetics of 5-FU were linear; at the highest S-1 dose level, 5-FU plasma
      peak concentrations reached 1 to 2 micromol/L, and the half-life of 5-FU was 3 to
      4 hours. A statistically significant relationship was observed between the
      severity of diarrhea and pharmacokinetic parameters of 5-FU. CONCLUSION: The
      recommended dose of S-1 in chemotherapy-naive or minimally chemotherapy-exposed
      patients is 40 mg/m(2) bid on 28 consecutive days, every 5 weeks. In heavily
      pretreated patients, the recommended dose is 35 mg/m(2) bid. Phase II trials are
      warranted in tumors known to be responsive to 5-FU treatment.

PMID- 10894880
TI  - Grading in marginal-zone lymphomas.

PMID- 10894879
TI  - Phase I and pharmacokinetic trial of gemcitabine in patients with hepatic or
      renal dysfunction: Cancer and Leukemia Group B 9565.
AB  - PURPOSE: To ascertain if hepatic or renal dysfunction leads to increased toxicity
      at a given dose of gemcitabine and to characterize the pharmacokinetics of
      gemcitabine and its major metabolite in patients with such dysfunction. PATIENTS
      AND METHODS: Adults with tumors appropriate for gemcitabine therapy and who had
      abnormal liver or renal function tests were eligible. Patients were assigned to
      one of three treatment cohorts: I-AST level less than or equal to two times
      normal and bilirubin level less than 1.6 mg/dL; II-bilirubin level 1.6 to 7.0
      mg/dL; and III-creatinine level 1.6 to 5.0 mg/dL with normal liver function.
      Doses were explored in at least three patients within each cohort. Gemcitabine
      and its metabolite were to be measured in the blood in all patients. RESULTS:
      Forty patients were assessable for toxicity. Transient transaminase elevations
      were observed in many patients but were not dose limiting. Patients with AST
      elevations tolerated gemcitabine without increased toxicity, but patients with
      elevated bilirubin levels had significant deterioration in liver function after
      gemcitabine therapy. Patients with elevated creatinine levels had significant
      toxicity even at reduced doses of gemcitabine, including two instances of severe
      skin toxicity. There were no apparent pharmacokinetic differences among the three
      groups or compared with historical controls. CONCLUSION: If gemcitabine is used
      for patients with elevations in AST level, no dose reduction is necessary.
      Patients with elevated bilirubin levels have an increased risk of hepatic
      toxicity, and a dose reduction is recommended. Patients with elevated creatinine
      levels seem to have increased sensitivity to gemcitabine, but the data are not
      adequate to support a specific dosing recommendation.

PMID- 10894881
TI  - Angiogenesis in neuroblastoma.

PMID- 10894882
TI  - Quality of life and cisplatin-gemcitabine chemotherapy.

PMID- 10894883
TI  - Phytoestrogens and adjuvant endocrine treatment of breast cancer.

PMID- 10894884
TI  - The role of human O(6)-alkylguanine-DNA alkyltransferase in promoting 1,2
      dibromoethane-induced genotoxicity in Escherichia coli.
AB  - The expression of the DNA repair protein human O(6)-alkylguanine-DNA
      alkyltransferase (AGT) in Escherichia coli strains GWR109 or TRG8 that lack
      endogenous AGT greatly increased the toxicity and mutagenicity of 1,2
      dibromoethane (DBE). Pretreatment of strain TRG8 expressing human AGT, which is
      permeable to exogenous drugs, with the AGT inhibitor O(6)-benzylguanine (BG)
      abolished the lethal and mutagenic effects of DBE, indicating that an active AGT
      is required for promoting DBE genotoxicity. This was confirmed by the observation
      that E. coli expressing either the C145A AGT mutant, which is inactive due to
      loss of the alkyl acceptor site, or mutants Y114E and R128A, which are inactive
      due to alteration of the DNA binding domain, did not enhance the action of DBE.
      However, the AGT mutant protein P138M/V139L/P140K, which is active in repairing
      methylated DNA but is totally resistant to inactivation by BG due to alterations
      in the active site pocket, was unable to enhance the genotoxicity of DBE.
      Similarly, other mutants, G156P, Y158H and K165R that are strongly resistant to
      BG, were much less effective than wild type AGT in mediating the genotoxicity of
      DBE. Mutant P140A, which is moderately resistant to BG, did increase mutations in
      response to DBE but was less active than wild type. These results suggest that
      human AGT is able to interact with a DNA lesion produced by DBE but, instead of
      repairing it, converts it to a more genotoxic adduct. This interaction is
      prevented by mutations that modify the active site of AGT to exclude BG.

PMID- 10894885
TI  - Inhibition of cigarette smoke-related DNA adducts in rat tissues by indole-3
      carbinol.
AB  - Indole-3-carbinol (I3C) found in various cruciferous vegetables has been shown to
      exert anti-carcinogenic activity in several target organs. In this study, we have
      investigated the effects of I3C on cigarette smoke-related lipophilic DNA adduct
      formation, potentially a key step in chemical carcinogenesis. Female Sprague
      Dawley rats were exposed to sidestream cigarette smoke in a whole-body exposure
      chamber for 6 h per day, 7 days a week for 4 weeks. Control animals received only
      vehicle while the intervention groups received I3C (1. 36 or 3.40 mmol/kg, b.wt.)
      daily by gavage starting from 1 week prior to smoke initiation until the end of
      the experiment. Analysis of tissue DNA by nuclease P1-mediated 32P-postlabeling
      showed one major and several minor smoke-related adducts in lung, trachea, heart
      and bladder. The high dose of I3C significantly inhibited the major adducts in
      lung (#5) and trachea (#3) by 55% each; minor adducts were slightly inhibited (20
      40%). The low dose of I3C showed lesser degree of inhibition (30-40%) in both
      lung and trachea; however, it was found statistically significant in lung only.
      The major smoke-related adduct in bladder (#2) was strongly inhibited (>65%) by
      high dose of I3C approaching adduct levels achieved in sham-exposed rats. A small
      but statistically significant decrease in the smoke-related DNA adduct (#5) in
      heart tissue was also observed by intervention with high dose I3C. Low levels (30
      50 adducts/10(10) nucleotides) of I3C-derived DNA adducts were also found in all
      the tissues examined although their significance remains unknown. These data show
      significant inhibition of cigarette smoke-related DNA adducts by I3C,
      particularly in the lung, trachea, and bladder.

PMID- 10894886
TI  - Genetic analysis of Raf1, Mdm2, c-Myc, Cdc25a and Cdc25b proto-oncogenes in 2',3'
      dideoxycytidine- and 1,3-butadiene-induced lymphomas in B6C3F1 mice.
AB  - We have previously identified activation of ras proto-oncogenes and inactivation
      of tumor suppressor genes including p53, p16(INK4a) and p15(INK4b) in 2',3'
      dideoxycytidine (ddC)- and/or 1,3-butadiene (BD)-induced lymphomas derived from
      B6C3F1 (C57BL/6xC3H/He) mice, indicating that alterations of ras signaling
      pathway, p53 and pRb growth control pathways are important in the development of
      these chemically induced lymphomas. However, there is still a subset of tumors
      that displayed no changes in these genes. Thus, we investigated whether the Raf1,
      Mdm2, c-Myc, Cdc25a and Cdc25b proto-oncogenes, which are implicated in the ras
      or p53 or pRb pathways, are alternative oncogenic target genes. Analyses of gross
      genomic alterations by Southern blots failed to reveal rearrangement or
      amplification in any of the tumors examined. Frequent point mutations on the
      substrate binding domain of the Raf1 gene has been reported in 1-ethyl-1
      nitrosourea (ENU)-induced murine lymphomas and lung tumors, along with a
      conspicuous lack of ras mutations [U. Naumann, I. Eisenmann-Tappe, U.R. Rapp, The
      role of raf kinases in development and growth of tumors, Recent Results Cancer
      Res., 143 (1997) 237-244]. To investigate whether Raf1 mutation is involved in
      our set of tumor especially those without ras mutations, the PCR-based single
      strand conformation analyses (SSCA) and direct DNA sequencing were employed. No
      mutations but four genetic polymorphisms between C57BL/6 and C3H/He were found,
      with two of them reported as point mutations previously (op. cit.). The
      polymorphisms were utilized for allelic loss study of Raf1 locus. Losses of
      heterozygosity were found in six of 31 BD-induced lymphomas. These results
      indicate that genetic alterations of c-Myc, Cdc25, Raf1 and Mdm2 proto-oncogenes
      may not be involved in the development of ddC- and BD-induced lymphomas and the
      inactivation of tumor suppressor gene(s) located close to Raf1 gene might be
      important in the development of a subset of BD-induced lymphomas.

PMID- 10894887
TI  - Increased nondisjunction of chromosome 21 with age in human peripheral
      lymphocytes.
AB  - Fluorescence in situ hybridization (FISH) on binucleated cells with chromosome
      specific DNA probes provides a convenient way to visualize reciprocal segregation
      patterns in daughter nuclei, and overcomes most problems related to the
      artefactual loss or gain of chromosomes that flaw chromosome preparations. In
      this study, FISH was employed to evaluate age- and sex-effects on spontaneous
      malsegregation, nondisjunction and loss of chromosome 21 in human lymphocytes
      after the first division in culture. A total of 68 healthy nonsmokers and
      nondrinkers of alcohol (37 males and 31 females) were grouped by age as Group I
      (0-10 years), Group II (20-30 years), Group III (40-50 years) and Group IV (60-70
      years), with at least seven subjects per group and sex. FISH with a pericentric
      chromosome 21 specific DNA probe was carried out on binucleated lymphocytes,
      cytokinesis-blocked by cytochalasin B (6 microg/ml for 26 h) at 44 h after
      initiation of cultures. Linear regression analyses demonstrated a significant age
      related increase in the frequency of micronuclei without chromosome 21 (MN
      21)(r=0.73, p<0.001 in females; r=0.69, p<0.001 in males) in all binucleated
      cells, with a steeper slope in females (0.1758) than in males (0. 1241). Analysis
      using the 2x2 chi-square (chi(2)) test on the frequencies of MN-21 showed
      significant age-related differences in both males and females, except males in
      Group III and Group IV (p>0. 05). A significant sex-related difference was found
      only in subjects over 60 years (p<0.05), with females having more MN-21 (12.57
      per thousand vs. 8.43 per thousand) than males. Loss of chromosome 21, occurring
      at mean levels of 0.38 per thousand in all binucleated cells and 0.24 per
      thousand in binucleated cells containing four FISH signals, was shown not to be
      age- or sex-related. A positive age-related increase in nondisjunction of
      chromosome 21 was shown in males (r=0.50, p<0.01), females (r=0.61, p<0.001) and
      all subjects (r=0.55, p<0.001) by linear regression analysis. An age effect was
      found only between children and adults (p<0.01 for females, p<0.05

PMID- 10894888
TI  - Sister-chromatid exchange frequencies in postmenopausal hormone replacement
      patients.
AB  - Our objective was to evaluate the frequency of sister-chromatid exchange (SCE)
      during hormone replacement therapy in postmenopausal women. Thirty-four
      asymptomatic postmenopausal women with a minimum 12 months since last menstrual
      period and surgical menopausal women were included in the study. Seventeen
      patients who were in spontaneous menopause were administered conjugated estrogen
      and medroxyprogesterone acetate (group A), and the others who were in surgical
      menopause were given 17beta-estradiol only (group B). Peripheral lymphocytes were
      obtained at the beginning and at the end of the third month of therapy. The mean
      age of the patients was 50. 67+/-4.79. There were statistically significant
      differences in terms of SCE frequencies between pre- and posttreatment levels of
      both groups (p<0.001 and p=0.003, respectively). It is likely that estrogens with
      or without progesterone have an effect in increased SCE frequency and this issue
      may be an evidence for the increased potential for malignancies.

PMID- 10894889
TI  - Tin-protoporphyrin potentiates arsenite-induced DNA strand breaks, chromatid
      breaks and kinetochore-negative micronuclei in human fibroblasts.
AB  - Numerous reports have shown that oxidative stress is involved in arsenite-induced
      genetic damage. Arsenite is also a potent inducer of heme oxygenase (HO)-1. To
      understand whether HO-1 could function as a cellular antioxidant and protect
      cells from arsenite injury, the effects of tin-protoporphyrin (SnPP), a
      competitive inhibitor of HO-1, on arsenite-induced genetic damage were examined
      in human skin fibroblasts (HFW). In the present study, we found that SnPP at 100
      microM significantly potentiated arsenite-induced cytotoxicity, DNA strand breaks
      (assayed by alkaline single cell gel electrophoresis(SCGE)), and chromatid
      breaks. Although arsenite alone mainly induced kinetochore-plus micronuclei (K(+)
      MN), SnPP only synergistically enhanced kinetochore-negative micronuclei (K(-)
      MN). The increase in K(-)-MN by SnPP cotreatment was consistent with the increase
      in DNA strand breaks and chromatid breaks caused by SnPP. However, at higher
      arsenite doses, K(+)-MN was significantly reduced by SnPP. Pretreatment of HFW
      cells with hemin, an inducer of HO-1, significantly attenuated the cytotoxicity
      of arsenite. Therefore, the present results suggest that HO-1 induction by
      arsenite plays certain roles in protecting cells from arsenite-induced injury.

PMID- 10894890
TI  - Mutation spectra induced by replication of two vicinal oxidative DNA lesions in
      mammalian cells.
AB  - Ionizing radiations often induce multiple and clustered DNA lesions at the site
      of DNA interaction. As a model, we have studied the toxicity and the mutagenicity
      of two adjacent oxidative bases as clustered DNA lesions in mammalian cells using
      shuttle vectors. The chosen oxidative lesions were 8-oxo-7,8-dihydroguanine, the
      formylamine residue resulting from the oxidation of a pyrimidine base and the
      tandem lesion 8-oxo-7,8-dihydroguanine/formylamine where both modifications are
      located at a vicinal position. A single-stranded DNA shuttle vector carrying a
      unique DNA lesion was constructed, transfected into simian COS7 cells and
      mutations induced after replication in mammalian cells were screened in bacteria.
      8-oxo-7,8-dihydroguanine, as expected, does not affect greatly survival (70%
      bypass) whereas formylamine and the tandem lesions are blocking alterations, DNA
      polymerase bypass being of 45% and 17%, respectively. Base insertion opposite the
      lesion was studied. Under our experimental conditions, replication of 8-oxo-7, 8
      dihydroguanine finally gives rise to guanine:cytosine pairing, rendering this
      lesion only slightly mutagenic. This is not the case for the formylamine that
      codes preferentially for adenine (71%). In addition, one-base deletions were
      observed targeted to the site to the lesion. Cytosine and thymine were inserted
      opposite the lesion with similar but low frequencies. Thus, coding properties of
      the formylamine render this residue very mutagenic when coming from the oxidative
      alteration of a cytosine. The coding properties of the tandem damage are a
      combination of the contribution of the two isolated lesions with a very high
      percentage of adenine insertion (94%) opposite the formylamine residue of the
      tandem lesion. The toxicity as well as the mutation spectrum of the tandem lesion
      allow us to speculate about the molecular mechanism with which the DNA polymerase
      replicates these two lesions.

PMID- 10894891
TI  - Identification of in vivo mutations in exon 5 of the human HPRT gene in a set of
      pooled T-cell mutants by constant denaturant capillary electrophoresis (CDCE).
AB  - Constant denaturant capillary electrophoresis (CDCE), based on co-operative DNA
      melting equilibria, has the resolving power to separate single nucleotide mutants
      from wild type sequences. We used this technique to study mutations in a 70-bp
      isomelting domain of the human HPRT gene, which included the entire exon 5 and
      its flanking splice donor and acceptor sites. Pooled samples of 6-thioguanine
      selected T-cell clones from 51 healthy donors representing a total of
      approximately 1000 individual HPRT mutants were analysed. Slow moving peaks from
      the heteroduplex part of the CDCE electropherograph were collected and subjected
      to a second round of PCR and CDCE analysis, followed by DNA sequencing. Five
      independent mutations were detected. Four were splicing errors; one insertion of
      CC and two G-->A transitions in the splice donor site of intron 5, and one G-->C
      transversion in the splice acceptor site of intron 4. The fifth mutation was a
      missense transversion, T389>G. A reconstruction experiment, in which DNA with
      known mutation was mixed with wild type DNA, showed the sensitivity of mutation
      detection to be better than 1:100 under the conditions used in this study. These
      results demonstrate the high sensitivity of the CDCE-method for mutation
      screening.

PMID- 10894892
TI  - Inducing somatic meiosis-like reduction at high frequency by caffeine in root-tip
      cells of Vicia faba.
AB  - Germinated seeds of Vicia faba were treated in caffeine solutions of different
      concentration for different durations to establish the inducing system of somatic
      meiosis-like reduction. The highest frequency of somatic meiosis-like reduction
      could reach up to 54.0% by treating the root tips in 70 mmol/l caffeine solution
      for 2 h and restoring for 24 h. Two types of somatic meiosis-like reduction were
      observed. One was reductional grouping, in which the chromosomes in a cell
      usually separated into two groups, and the role of spindle fibers did not show.
      The other type was somatic meiosis, which was analogous to meiosis presenting in
      gametogenesis, and chromosome pairing and chiasmata were visualized.

PMID- 10894893
TI  - Rapid detection of radiation-induced chromosomal aberrations in lymphocytes and
      hematopoietic progenitor cells by mFISH.
AB  - Structural chromosome aberrations (SCAs) are sensitive indicators of a preceding
      exposure of the hematopoietic system to ionizing radiation. Cytogenetic
      investigations have therefore become routine tools for an assessment of absorbed
      radiation doses and their biological effects after occupational exposure or
      radiation accidents. Due to its speed and ease of use, fluorescence in situ
      hybridization (FISH) with whole chromosome painting (WCP) probes has become a
      method of choice to visualize SCAs. Until recently, this technique was limited to
      a rather small number of chromosomes, which could be tested simultaneously. As a
      result, only a fraction of the structural aberrations present in a sample could
      be detected and the overall dose effect had to be calculated by extrapolation.
      The recent introduction of two genome-wide screening techniques in tumor
      research, i.e., Spectral Karyotyping (SKY) and multicolor FISH (mFISH) now allows
      the detection of translocations involving any two non-homologous chromosomes. The
      present study was prompted by our desire to bring the power of mFISH to bear for
      the rapid identification of radiation-induced SCAs. We chose two model systems to
      investigate the utility of mFISH: lymphocytes that were exposed in vitro to 3 Gy
      photons and single hematopoietic progenitor cell colonies isolated from a
      Chernobyl victim 9 years after in vivo exposure to 5.4 Sv.In lymphocytes, we
      found up to 15 different chromosomes involved in rearrangements indicating
      complex radiation effects. Stable aberrations detected in hematopoietic cell
      colonies, on the other hand, showed involvement of up to three different
      chromosomes. These results demonstrated that mFISH is a rapid and powerful
      approach to detect and characterize radiation-induced SCAs in the hemopoietic
      system. The application of mFISH is expected to result in a more detailed and,
      thus, more informative picture of radiation effects. Eventually, this technique
      will allow researchers to rapidly delineate chromosomal breakpoints and
      facilitate the identification of the genes involved in radiation tumorigenesis.

PMID- 10894894
TI  - Detection of mutation of the p53 gene with high sensitivity by fluorescence-based
      PCR-SSCP analysis using low-pH buffer and an automated DNA sequencer in a large
      number of DNA samples.
AB  - Detection of mutations in genes responsible for hereditary diseases or tumors is
      important clinically. It is necessary to establish a simple technique for
      screening mutations in large numbers of samples. The polymerase chain reaction
      single-strand conformation polymorphism (PCR-SSCP) method has proved to be a
      useful technique for analyzing mutations or DNA polymorphisms. Non-radioisotopic
      versions using fluorescent dye and an automated DNA sequencer have also been
      exploited to extend this technique into the clinical field. We have examined
      mutations of exons 5-9 of the p53 gene in 112 colorectal, 28 esophageal and 33
      hepatocellular carcinomas by fluorescence-based PCR-SSCP (F-SSCP) under various
      conditions. We found 64 types of mutations in 63, 17 and 12 cases of colon,
      esophageal and hepatocellular carcinomas by F-SSCP. We determined the sequence of
      all samples, and confirmed that all mutations were successfully detected by F
      SSCP. With the low-pH buffer system, 61 types of mutants were detected, while 51
      types were detected by TBE and 57 types were detected by TBE with glycerol gel.
      The polyacrylamide gel in TME or TBE without glycerol was tough and could be used
      repeatedly, but the glycerol containing gel was fragile and could not stand
      repeated use. Thus, use of a low-pH buffer in the electrophoresis of F-SSCP is
      simpler and better at detecting mutations than the conventional TBE buffer
      system. We believe that low-pH F-SSCP analysis is an efficient and powerful
      technique for examination of a large number of samples, in particular clinical
      specimens obtained by biopsy or surgery.

PMID- 10894895
TI  - Nickel(II) induces microsatellite mutations in human lung cancer cell lines.
AB  - Nickel(II) is a human carcinogen causing respiratory cancers. The purpose of this
      study was to determine whether Ni(II) may induce microsatellite mutations in
      human cells. We transfected the three human lung tumor cell lines A427, HCC15 and
      NCI-H2009 with a mammalian expression vector containing a (CA)(13) repeat in the
      coding sequences of the reporter hygromycin gene (hyg). A total of 33 clones
      carrying the integrated vector derived from the three cell lines was investigated
      for spontaneous and Ni(II)-induced hygromycin-resistant (hyg(r)) reversion
      mutants. Significantly higher frequencies of hyg(r) reversion mutations were
      observed in Ni(II)-treated cells (NCI-H2009 and HCC-15) than control cells. In
      the majority of the colonies hyg(r) phenotype was due to mutations within the
      integrated (CA) repeat sequence. The type of mutations consisted of both
      contraction and expansion of the (CA) repeat unit. The finding that Ni(II)
      promotes microsatellite mutations raises the possibility that genetic instability
      may be a mechanism involved in nickel carcinogenesis.

PMID- 10894896
TI  - Interpretation of mutational spectra from different genes: analyses of PhIP
      induced mutational specificity in the lacI and cII transgenes from colon of Big
      Blue rats.
AB  - The cII assay provides an alternative choice to the lacI transgene for mutational
      studies involving Big Blue(R) transgenic mice and rats, or permits the evaluation
      of mutational responses in both genes. Here, we compare the mutational response
      of the cII gene from colon of Big Blue(R) F344 rats treated with a dietary
      mutagen and animal carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP), to those previously determined in the lacI transgene from colon of the
      same group of animals. A cursory inspection of PhIP-induced mutational spectra
      (MS) in cII and lacI suggests that the two transgenes respond differently to PhIP
      induced mutation. However, a more thorough analysis of the MS in the two
      transgenes, including consideration of the number of mutational target sequences
      in each gene and nearest neighbor analyses of mutated nucleotides, indicates that
      PhIP-induced mutational specificity is similar in both genes. The evaluation of
      PhIP-induced mutational responses in these two transgenes serves as a model for
      intergenic mutational analyses.

PMID- 10894897
TI  - Cellular phenotypes of age-associated skeletal muscle mitochondrial abnormalities
      in rhesus monkeys.
AB  - Rhesus monkey vastus lateralis muscle was examined histologically for age
      associated electron transport system (ETS) abnormalities: fibers lacking
      cytochrome c oxidase activity (COX(-)) and/or exhibiting succinate dehydrogenase
      hyperreactivity (SDH(++)). Two hundred serial cross-sections (spanning 1600
      microm) were obtained and analyzed for ETS abnormalities at regular intervals.
      The abundance and length of ETS abnormal regions increased with age.
      Extrapolating the data to the entire length of the fiber, up to 60% of the fibers
      were estimated to display ETS abnormalities in the oldest animal studied (34
      years) compared to 4% in a young adult animal (11 years). ETS abnormal phenotypes
      varied with age and fiber type. Middle-aged animals primarily exhibited the COX(
      ) phenotype, while COX(-)/SDH(++) abnormalities were more common in old animals.
      Transition region phenotype was affected by fiber type with type 2 fibers first
      displaying COX(-) and then COX(-)/SDH(++) while type 1 fibers progressed from
      normal to SDH(++) and then to COX(-)/SDH(++). In situ hybridizations studies
      revealed an association of ETS abnormalities with deletions of the mitochondrial
      genome. By measuring cross-sectional area along the length of ETS abnormal
      fibers, we demonstrated that some of these fibers exhibit atrophy. Our data
      suggest mitochondrial (mtDNA) deletions and associated ETS abnormalities are
      contributors to age-associated fiber atrophy.

PMID- 10894898
TI  - Enhancing effect of saccharides on the mutagenicity of 2-chloro-4
      methylthiobutanoic acid.
AB  - The mutagenicity of 2-chloro-4-methylthiobutanoic acid (CMBA), a nitrite-treated
      Sanma fish mutagen, in Salmonella typhimurium TA100 was enhanced by addition of D
      glucose during the CMBA-treatment. Several other monosaccharides also enhanced
      the mutagenicity of CMBA, and the order of the enhancing potency was found to be
      D-mannose, D-glucose>D-fructose, D-ribose, D-galactose. A disaccharide, maltose,
      showed only little enhancement. No enhancement was found with L-glucose. We
      investigated whether saccharides affect uptake of [methyl-14C]CMBA into S.
      typhimurium TA100. Saccharides which enhanced CMBA-induced mutagenesis increased
      the uptake. L-Glucose did not enhance the uptake. There was good correlation
      between the enhanced mutagenesis and increased radioactivity in Salmonella,
      suggesting that the enhancing effect of monosaccharide on the CMBA-induced
      mutagenesis results from the enhanced uptake of the mutagen into bacteria.

PMID- 10894899
TI  - Elevated cardiac troponin levels do not predict adverse outcomes in hospitalized
      patients without clinical manifestations of acute coronary syndromes.
AB  - The prognostic significance of elevated cardiac troponin levels (CTL) in
      hospitalized patients with no other evidence of myocardial ischemia or injury is
      largely unknown. Fifty patients (mean age 61 +/- 15 years, 15 women) out of 580
      consecutive hospitalized patients were selected based on normal CK-MB and at
      least 3-fold increase of CTL. The medical charts of these patients were reviewed
      and a 1-year follow-up was performed. The most frequent admission diagnoses were
      exacerbation of congestive heart failure (22%), stroke (20%) followed by
      respiratory failure (6%), cirrhosis (6%), gastrointestinal bleeding (6%), end
      stage renal disease (4%), atrial fibrillation (4%) and metastatic malignancies
      (4%). Abnormal CTL prompted a cardiology consult in 48% of patients, an
      echocardiogram in 44%, myocardial perfusion study in 10% and coronary angiography
      in 1 patient. Of 21 deaths, only 1 was related to an acute coronary event. The
      measurement of CTL in patients without definite clinical or electrocardiographic
      evidence of myocardial ischemia and with a wide spectrum of clinical diagnoses
      does not predict in-hospital and at 1 year cardiovascular complications and/or
      cardiac death.

PMID- 10894900
TI  - Soluble VCAM-1 and E-selectin, but not ICAM-1 discriminate endothelial injury in
      patients with documented coronary artery disease.
AB  - It has been shown that endothelial cell adhesion molecules play an important role
      in the development of coronary atherosclerosis and inflammatory disease. We
      sought to test whether soluble vascular cell adhesion molecule-1 (VCAM-1),
      intercellular adhesion molecule-1 (ICAM-1) and E-selectin are increased in
      patients with documented coronary artery disease (CAD). Plasma levels of VCAM-1,
      ICAM-1 and E-selectin were measured in 40 patients with documented CAD, 20
      subjects with angiographically documented normal coronary arteries, and 14
      healthy volunteers. Patients with documented CAD exhibited significant elevation
      of VCAM-1 (535 +/- 227.1 ng/ml, p = 0.0001), E-selectin (69.4 +/- 29.4 ng/ml, p =
      0.006), but not ICAM-1 (320.5 +/- 65.1 ng/ml, p = 0.9) concentrations as compared
      to subjects with normal coronary arteries (252.3 +/- 79.8, 49.7 +/- 22.0 and
      311.4 +/- 40.2 ng/ml), and healthy controls (110.0 +/- 17.7, 29.0 +/- 2.0 and
      237.5 +/- 46.5 ng/ml), respectively. Soluble markers of endothelial injury are
      not uniformly increased in patients with documented CAD as compared to those with
      normal coronary arteries and healthy controls. However, VCAM-1 and E-selectin,
      but not ICAM-1 could identify endothelial injury in such patients.

PMID- 10894901
TI  - Aetiology of heart failure as seen from a National Cardiac Referral Centre in
      Africa.
AB  - 572 consecutive patients with heart failure referred to the National
      Cardiothoracic Centre, Accra, Ghana, over a 4-year period were evaluated for the
      aetiology of heart failure using two-dimensional Doppler echocardiography with
      colour flow. The mean age of the subjects with heart failure was 42.3 +/- 0.9
      years. The male to female ratio was 1.2:1.0. Combined heart failure was seen in
      50.5% of subjects. Peak incidence of heart failure occurred in the 5th decade.
      The main causes of heart failure were hypertension (21.3%; n = 122), rheumatic
      heart disease (20.1%; n = 115) and cardiomyopathy (16.8%; n = 96). Congenital
      heart disease and coronary artery disease accounted for 9.8 and 10% of cases,
      respectively. The commonest rheumatic valvular lesion was mitral regurgitation
      (78%). Dilated cardiomyopathy was the commonest form of idiopathic cardiomyopathy
      (67.7%; n = 65). Endomyocardial fibrosis and hypertrophic cardiomyopathy
      accounted for 22.9% (n = 22) and 9.4% (n = 9), respectively, of cardiomyopathies.

PMID- 10894902
TI  - Evaluation of brain natriuretic peptide in the diagnosis of heart failure.
AB  - A diagnosis of heart failure (HF) can be difficult, especially in patients with
      mild symptomatology. The purpose of this study was to evaluate the significance
      of brain natriuretic peptide (BNP) in the diagnosis of HF with systolic or
      isolated diastolic ventricular dysfunction. One hundred patients and 9 controls
      were included in the study. Eighty-five patients were diagnosed with HF, based on
      clinical and echocardiographic findings. BNP levels were accurate for the
      diagnosis of HF, with an area under the receiver operating characteristic (ROC)
      curve (AUC) of 0.92. In addition, BNP levels showed an excellent accuracy for the
      diagnosis of isolated diastolic HF (AUC = 0.89). These data suggest that the
      measurement of BNP levels may be helpful in the diagnosis of HF and in selecting
      patients for further evaluation. Furthermore, BNP measurement can play an
      important role in the diagnosis of isolated diastolic HF.

PMID- 10894903
TI  - Using internal jugular pulsations as a manometer for right atrial pressure
      measurements.
AB  - External jugulars are not reliable as an indication of right atrial pressure
      because of their passage through two right angles and also because they are often
      not visible. The top level of internal jugular pulsations which are transmitted
      to the skin of the neck serves as a pulsation manometer. A standard chest angle
      of 45 degrees and a standard zero at the sternal angle can be used together with
      a centimeter ruler to give a useful measurement of jugular venous pressure. The
      use of a carpenter level (spirit level) and a round-bottomed tongue blade
      measured off in centimeters will allow accurate follow-up. An increase in tone
      volume can be detected by the abdominal compression test or abdominojugular test
      (also known by the outdated terminology of hepatojugular reflux).

PMID- 10894904
TI  - Changes of plasma tissue factor and tissue factor pathway inhibitor antigen
      levels and induction of tissue factor expression on the monocytes in coronary
      artery disease.
AB  - BACKGROUND: Several studies have shown that thrombosis and inflammation play an
      important role in the pathogenesis of coronary artery disease (CAD). Tissue
      factor (TF) is responsible for the thrombogenicity of the atherosclerotic plaque
      and plays a key in triggering thrombin generation. The aim of this study was to
      assess the levels of TF and tissue factor pathway inhibitor (TFPI) in patients
      with angiographically documented CAD and also to evaluate TF induction on
      monocytes in vitro in the presence of these plasmas from patients with CAD.
      METHODS: Plasma antigen levels of soluble TF and TFPI were measured in 65 CAD
      patients and 22 healthy controls. Surface TF expression on monocytes from a
      healthy donor treated with plasma samples was evaluated by flow cytometry with a
      direct double-color immunofluorescence technique. RESULTS: Significantly elevated
      levels of both TF and TFPI were found in CAD patients compared with healthy
      controls (303.6 +/- 134.1 vs. 187.3 +/- 108.7 pg/ml, p < 0.05; 85.2 +/- 48.6 vs.
      65.0 +/- 29.0 ng/ml, p < 0.05). By flow cytometry, monocytes from a healthy donor
      displayed higher TF antigen expression when incubated in the presence of CAD
      plasmas than in control plasmas (34.6 +/- 10.7 vs. 23.2 +/- 10.2%, p < 0.05).
      CONCLUSIONS: The high levels of circulating TF are present in CAD, which were not
      sufficiently inhibited by the elevated TFPI plasma levels. Although the source of
      circulating TF is unclear, TF induction of monocytes by plasma from CAD patients
      may contribute to the hypercoagulable state.

PMID- 10894905
TI  - Preoperative predictors of late postoperative outcome among patients with
      nonischemic mitral regurgitation with 'high risk' descriptors and comparison with
      unoperated patients.
AB  - Among patients with chronic nonischemic mitral regurgitation (MR), high short
      term mortality risk can be identified by left (LV) and/or right ventricular (RV)
      ejection fraction (EF) criteria (LVEF </=45% and/or RVEF </=30%). Mitral valve
      replacement or repair (MVR) significantly improves outcome in this subgroup, but
      predictors of late postoperative survival are not known, and the benefit of MVR
      has not been defined in patients matched for severity of LV and RV dysfunction.
      Therefore, prospective assessment of 14 consecutive high risk MR patients was
      performed before MVR and during 9 years (average) postoperatively to define
      echocardiographic and radionuclide angiographic predictors of survival; survival
      also was evaluated in a contemporaneous series of 9 high risk unoperated MR
      patients, and in subgroups of operated and unoperated patients matched for EF. Of
      14 MVR patients, 4 died (3 cardiac: 1 sudden, 2 congestive heart failure). Only
      preoperative RVEF </=20% significantly predicted postoperative deaths (rest p =
      0.032; exercise p = 0.05). Of 9 unoperated patients, 8 died. Mortality risk of
      unoperated patients remained higher than that of MVR patients when groups were
      matched for preoperative LVEF (p = 0.0001). Among patients with RVEF >20%, MVR
      significantly improved survival versus medical treatment (rest: p < 0.0001,
      exercise: p = 0.0003). In high risk MR patients, MVR improves survival;
      preoperative RV performance can define subgroups with different long-term
      postoperative survival.

PMID- 10894906
TI  - Cardiac dysfunction and long-term prognosis in patients with nonobstructive
      hypertrophic cardiomyopathy and abnormal (123)I-15- (p-Iodophenyl)-3(R,S)
      methylpentadecanoic acid myocardial scintigraphy.
AB  - To evaluate the relationship between myocardial scintigraphic abnormalities based
      on (123)I-radioiodinated 15-(p-iodophenyl)-3(R, S)-methylpentadecanoic acid
      (BMIPP) uptake and cardiac function and the relationship between these
      abnormalities and long-term prognosis in patients with hypertrophic
      cardiomyopathy (HCM), 27 patients with nonobstructive HCM underwent BMIPP
      myocardial scintigraphic study, echocardiography, and exercise radionuclide
      study. Based on the extent of BMIPP scintigraphic defects, the patients were
      divided into two groups: Group A (n = 19) patients had no or small defects, and
      group B (n = 8) patients had moderate to large defects. Cardiac events were
      recorded over an average period of 64 months. The left ventricular end-diastolic
      and end-systolic dimensions were significantly greater in group B than in group
      A. The fractional shortening in group B was less than in group A (p = 0.0002).
      The BMIPP score and fractional shortening at rest correlated significantly (p <
      0.05). The BMIPP score and the change in ejection fraction between rest and peak
      exercise correlated significantly (p < 0.05). While only 1 cardiac event occurred
      in the 19 patients in group A during a mean follow-up period of 64 months, 6
      cardiac events occurred in the 8 patients in group B. The 84-month event-free
      survival rate was 94.4% in group A and 14.6% in group B (p < 0.01). These results
      suggest that patients with HCM and moderate to large defects as assessed by BMIPP
      myocardial scintigraphy have decreased cardiac function and a poor prognosis.

PMID- 10894907
TI  - Combining necrosis and platelet markers for perfecting myocardial infarction rule
      out: how close are we?
AB  - Each year, at least 5 million patients in the United States present to hospital
      emergency departments with the complaint of chest pain, and more than 10% of them
      will be diagnosed with acute myocardial infarction. One of the foremost tasks of
      the emergency department physician is to avoid unnecessary admissions and
      concomitantly to minimize the number of patients discharged home inappropriately.
      Currently available diagnostic tools, including the electrocardiogram and
      myocardial markers, have several shortcomings, including low specificity, and
      delayed sensitivity for the timely detection of myocardial necrosis. Therefore,
      the search for better methods of rapidly identifying patients with unstable
      coronary syndromes is one of the utmost priorities of modern emergency medicine.
      Available biochemical diagnostic tools are discussed in this review, focusing on
      the potential benefits of combining myocardial necrosis markers with indicators
      of platelet activation. It is hypothesized that such a combined approach may be
      more powerful in myocardial infarction risk stratification than separate marker
      determination.

PMID- 10894908
TI  - The problem of ventricular dysrhythmias and sudden death mortality in heart
      failure: the impact of current therapy.
AB  - Congestive heart failure (CHF), one of the few cardiovascular conditions
      increasing in incidence and prevalence, is characterized by high morbidity and
      mortality. Up to 50% of the mortality is attributable to dysrhythmic sudden
      death. Risk stratification to identify those most susceptible to sudden death
      remains imperfect. The advances in CHF therapeutics and management over the past
      16 years have had a favorable impact on CHF mortality including sudden death. The
      role of amiodarone and implantable cardioverter-defibrillator intervention is
      evolving and discussed in the context of current CHF management and available
      trials.

PMID- 10894909
TI  - Dependency of premature ventricular contractions on heart rate and circadian
      rhythms during childhood.
AB  - The aim of the present study was to identify and quantify the rate dependence of
      premature ventricular contractions (PVC) during childhood. A 24-hour Holter
      recording was performed in 16 consecutive children, aged 22 days to 11 years
      (mean age 5.6 years), with frequent (>5,000/day), isolated monomorphic PVC. Those
      PVC were identified and the length of the preceding sinus cycle was measured. The
      values were ordered into 50-ms class intervals, and the percentage of PVC for
      each class was calculated and then analyzed by linear regression analysis. On the
      basis of the significance of the p value, and the positive or negative value of
      the slope, we identified a tachycardia-enhanced, a bradycardia-enhanced, and an
      indifferent pattern. Chronobiologic analysis was made by the cosinor method. All
      the patients had upper and lower limits of cycle length beyond which PVC
      disappeared. A tachycardia-enhanced pattern was present in 7 patients and an
      indifferent one in 9 patients. In the latter a second-degree polynomial
      correlation was systematically found. Children but not infants had a significant
      circadian variation in the frequency of PVC with a very variable time of highest
      incidence. In conclusion, it is possible to identify a circadian rhythm of PVC
      and a spontaneous trend between their incidence and the length of the preceding
      cardiac cycle in children.

PMID- 10894910
TI  - Transvenous pacemaker leads do not worsen tricuspid regurgitation: a prospective
      echocardiographic study.
AB  - Limited prospective data are available regarding the influence of pacemaker leads
      on tricuspid valve function. To examine the true incidence of these
      complications, 35 patients were prospectively examined by two-dimensional and
      Doppler echocardiography before and after implantation of either a permanent
      pacemaker or an automatic implantable cardioverter-defibrillator. Of the 35
      patients imaged preoperatively, the amount of tricuspid regurgitation (TR) was
      judged as normal or trivial in 15 (43%), mild in 10 (29%), moderate in 8 (23%),
      and severe in 2 (6%). Following electrode implantation, TR was noted to be normal
      or trivial in 13 (38%), mild in 15 (48%), moderate in 6 (17%) and severe in 1
      (3%). We conclude that implantation of permanent right ventricular electrodes is
      not usually associated with an acute worsening of tricuspid regurgitation in most
      patients.

PMID- 10894911
TI  - Prognostic role of on-line vectorcardiography as regards repeat revascularization
      after successful coronary angioplasty.
AB  - This study evaluated the prognostic significance of continuous on-line
      vectorcardiography (VCG) during elective coronary angioplasty (percutaneous
      transluminal coronary angioplasty, PTCA). Patients (n = 192, mean age 58 +/- 10),
      treated with elective and initially successful PTCA, were included. VCG
      monitoring was started before start of the PTCA procedure and was carried out
      during the entire procedure. ST vector magnitude (ST-VM) was monitored. A 6-month
      follow-up was obtained. Main outcome measures were the frequency of cardiac
      events and revascularization during follow-up. During follow-up, 1 patient died,
      6 suffered a nonfatal myocardial infarction and 50 were revascularized.
      Angiography revealed restenosis in 88% of the patients who had a
      revascularization. In the total patient group, the VCG predictor of
      revascularization was the total ischemic time of all ST-VM episodes (p = 0.05).
      Clinical predictors of revascularization were diabetes mellitus (p < 0.01), a
      more severe type of lesion (type B; p < 0.01), percent post-PTCA stenosis (p <
      0.05), nominal balloon size (p < 0.01), maximum balloon pressure (p < 0.05) and
      no stent implanted (p < 0.001). In a multivariate analysis all the above
      significant univariate variables of revascularization were entered. Total
      ischemic time of ST-VM (p < 0.01) was the best variable giving independent
      prognostic information. In the nonstent group, total ischemic time of ST-VM (p <
      0.01) was the only independent predictor of a further revascularization. In
      conclusion, VCG monitoring during elective PTCA gives on-line information that
      identifies patients at an increased risk of a revascularization during 6 months
      after the initial procedure.

PMID- 10894912
TI  - Cardiogenic shock: single center experience with and without on-site
      catheterization facilities.
AB  - BACKGROUND: The beneficial effect of on-site catheterization facilities on the
      survival of all patients with myocardial infarction complicated by cardiogenic
      shock has been questioned. Our objective was to evaluate the impact of the
      availability of on-site catheterization facilities on the outcome of unselected
      patients with cardiogenic shock. METHODS AND RESULTS: We studied the hospital
      records of 70 consecutive patients with cardiogenic shock admitted to our
      intensive coronary care unit during 1990-1996, and compared two groups of
      patients: those admitted before (n = 34) and after (n = 36) the opening of our
      catheterization laboratory. Patients admitted when the catheterization laboratory
      was available were of similar age, but included fewer males and fewer patients
      with prior myocardial infarction. Following the activation of the catheterization
      laboratory, utilization rates of coronary angiography, percutaneous transluminal
      coronary angioplasty and intra-aortic balloon pump increased, compared with the
      previous period. However, there was no improvement in in-hospital (88 vs. 83%; p
      = 0.7) and 30-day mortality (91 vs. 86%; p = 0.7) before versus after the
      activation of our catheterization laboratory. Twelve patients selected to cardiac
      catheterization (9 underwent percutaneous transluminal coronary angioplasty)
      experienced lower in-hospital and 30-day mortality compared with patients who
      were not selected (58 vs. 96, and 67 vs. 96%, respectively; p < 0.02).
      CONCLUSIONS: Following the activation of the catheterization laboratory, the
      mortality of the entire population of cardiogenic shock patients remained
      relatively unchanged. Still, a small subgroup of these patients selected for
      urgent cardiac catheterization had a lower mortality compared with patients who
      were not selected.

PMID- 10894913
TI  - Increased blood vascular endothelial growth factor levels in patients with acute
      myocardial infarction.
AB  - Vascular endothelial growth factor (VEGF) is a growth factor for vascular
      endothelial cells in vitro. The present study was designed to determine whether
      serum VEGF levels increase in patients with acute myocardial infarction (AMI)
      compared with patients with stable exertional angina and control subjects, and to
      examine the serial changes of serum VEGF levels in patients with AMI. We examined
      serum VEGF levels by using antibody prepared from serum immunized with human
      VEGF(121). The serum VEGF level (pg/ml) was higher (p < 0. 0001) on admission in
      the patients with AMI (177 +/- 19) than in those with stable exertional angina
      (61 +/- 7) and control subjects (62 +/- 6). The serum VEGF level (pg/ml) of the
      patients with AMI was 177 +/- 19 on admission, 125 +/- 9 on day 3, 137 +/- 11 on
      day 5, 242 +/- 18 at 1 week, and 258 +/- 22 at 2 weeks after admission. The value
      was higher on admission than on day 3 after admission (p = 0.014), the values
      were higher at 1 week and 2 weeks than on admission, on day 3, and 5 (p < 0.01).
      Furthermore, there were correlations between peak VEGF levels at 1 week or 2
      weeks after admission and peak creatine kinase levels. The increase of VEGF on
      admission in the patients with AMI may be due to the hypoxia of acute myocardial
      ischemia. The elevation at 1 week and 2 weeks from the onset may cause the
      development of collateral circulation in relation to the healing of the
      infarction site.

PMID- 10894914
TI  - Clinical symptoms and myocardial infarction in left bundle branch block patients.
AB  - In patients with left bundle branch block (LBBB) and acute chest pain, the
      association between the clinical presentation and the diagnosis of myocardial
      infarction has not been investigated. We sought to identify features in the
      clinical history of patients with LBBB and acute cardiopulmonary symptoms that
      predict myocardial infarction among candidates for reperfusion therapy. We
      retrospectively studied a consecutive cohort of 75 patients (94 presentations)
      who presented to a university emergency department from 1994 to 1997 with LBBB on
      initial electrocardiogram (ECG) and acute chest pain of >/=20 min duration or
      acute pulmonary edema. Among the 94 presentations meeting criteria for the
      cohort, 26 (28%) had confirmed myocardial infarction. Coronary heart disease risk
      factors, past cardiac history, prior LBBB on the ECG, and presenting symptoms did
      not predict whether patients were having myocardial infarction. The clinical
      history was not effective at distinguishing LBBB patients with myocardial
      infarction among patients who appeared to be candidates for acute reperfusion
      therapy.

PMID- 10894915
TI  - Utility of positron emission tomography in predicting improved left ventricular
      ejection fraction after coronary artery bypass grafting among patients with
      ischemic cardiomyopathy.
AB  - The objective of this study was to determine whether preoperative estimates of
      regional myocardial uptake of (18)-F-fluorodeoxyglucose (FDG) could predict
      postoperative improvement in ejection fraction in patients undergoing coronary
      artery bypass grafting (CABG) for ischemic cardiomyopathy. 20 consecutive
      patients [left ventricular ejection fraction (LVEF) </=27%] were referred for
      preoperative positron emission tomography (PET) to measure regional myocardial
      FDG uptake and were deemed candidates for CABG. All individuals had technically
      adequate vessels and significant viability. The left anterior descending (LAD)
      coronary artery was severely diseased in all patients. Because of the importance
      of the anterior wall to overall ventricular performance, FDG uptake was
      semiquantitated in those regions and related to postoperative LVEF. 17 patients
      underwent CABG with an uneventful recovery. LVEF increased from 22 +/- 4 to 26 +/
      7% 2 weeks postsurgery (p < 0.05), with >/=5% change noted in 7 patients (group
      1) and <5% noted in 10 patients (group 2). No preoperative or perioperative
      clinical variable could predict those with improved ventricular function. The
      relative amount of FDG uptake in the anterior wall was higher in group 1 compared
      with group 2 (93 +/- 9 vs. 81 +/- 13%; p < 0.05) and correlated with the change
      in LVEF post-CABG (r = 0.50; p < 0.05). >88% of FDG uptake in the LAD region had
      a positive predictive accuracy of 67% and negative predictive accuracy of 88% for
      improved LVEF postbypass. Late follow-up estimates of LVEF (median of 10 months)
      showed that early changes in function were sustained. In summary, among patients
      with severe coronary artery disease and depressed LVEF, ventricular function may
      improve early postrevascularization. PET estimates of relative FDG uptake in the
      anterior wall help predict those individuals who are likely to have the greatest
      increment in LVEF.

PMID- 10894916
TI  - Integrated backscatter for quantification and risk stratification of blood
      stagnation in left atrial appendages of patients with rheumatic mitral stenosis.
AB  - This study was designed to quantify the blood stagnation in left atrial
      appendages (LAA) of patients with rheumatic mitral stenosis, and to stratify the
      risk of spontaneous echo contrast (SEC) for thrombus formation. A total of 45
      patients were enrolled in this study. Thirty of the 45 patients had rheumatic
      mitral stenosis. All the above patients were evaluated for LAA contractility by
      transesophageal echocardiography. Acoustic density of the stagnant blood was
      assessed using the integrated backscatter (IBS) mode. Multivariate linear
      regression analysis showed that the significant independent variables determining
      relative IBS in LAA were the mitral valve area (p = 0.02) and the atrial
      fibrillation rhythm (p = 0.0003). In patients with mitral stenosis, the IBS in
      LAA correlated well with the presence of thrombus (p = 0.004) and SEC (p =
      0.002). Using the relative IBS in LAA with 6.8 dB as the cutoff value, the
      diagnostic sensitivity, specificity, positive predictive value, negative
      predictive value and accuracy of SEC formation in LAA was 83, 86, 95, 60 and 83%,
      respectively. Using the relative IBS in LAA with 10.0 dB as the cutoff value, the
      diagnostic sensitivity, specificity, positive predictive value, negative
      predictive value and accuracy of SEC with thrombus formation in LAA was 80, 80,
      67, 89 and 80%, respectively. In conclusion, the blood stasis in LAA can be
      objectively quantified using IBS. Utilizing different cutoff values, the acoustic
      densitometry in LAA enables identification of stagnant blood which represents a
      risk for the development of either SEC only or SEC with thrombus formation.

PMID- 10894917
TI  - Reversible systolic dysfunction in an elite athlete.

PMID- 10894918
TI  - Dangerous impact--commotio cordis.
AB  - Sudden death following blunt chest trauma is a frightening occurrence known as
      'commotio cordis' or 'concussion of the heart'. It is speculated that commotio
      cordis could be caused by ventricular fibrillation secondary to an impact-induced
      energy that was transmitted via the chest wall to the myocardium during its
      vulnerable repolarization period. We describe a survivor of commotio cordis
      caused by a baseball. In this patient, an initial ventricular fibrillation was
      documented and converted by direct current defibrillation. Serial
      electrocardiographic changes (bifascicular conduction block and T wave inversion
      in precordial leads) were noticed in this patient. Our case suggested that
      coronary vasospasm might also play a role in commotio cordis.

PMID- 10894919
TI  - Extensive thrombus formation in the right ventricle due to a rare combination of
      arrhythmogenic right ventricular cardiomyopathy and heterozygous prothrombin gene
      mutation G20210 A.
AB  - Arrhythmogenic right ventricular cardiomyopathy is a rare heart muscle disease
      characterized by right and often left ventricular myocardial atrophy and
      fibrofatty replacement. Heart failure, arrhythmias and sudden death are
      characteristic complications. We observed a female in whom arrhythmogenic right
      ventricular cardiomyopathy was diagnosed due to presyncopes and dyspnea on
      exertion. A left ventricular thrombus was found echocardiographically, which
      disappeared with oral anticoagulation. Subsequently, however, extensive thrombus
      formation in the dilated akinetic right ventricle occurred which was resistant to
      combined treatment with heparin and oral anticoagulation. Thrombophilia screening
      showed a mutant prothrombin 20210A allele which is an inherited coagulopathy
      associated with increased plasma levels of prothrombin and increased risks of
      mainly venous thrombosis. The patient developed endstage biventricular heart
      failure and underwent heart transplantation within 3 months after thrombus
      formation in the right ventricle was diagnosed. In the explanted heart, the
      thrombus in the right ventricle was impressively large and calcified. In patients
      with unusual thrombus formation in the heart, coagulopathy may be associated and
      should be excluded.

PMID- 10894921
TI  - Amyotrophic lateral sclerosis with a 'pseudo-infarction' pattern on the
      electrocardiograph. A case report.
AB  - Amyotrophic lateral sclerosis (ALS) is a motor neuron disease involving both the
      upper and lower motor neurons in the brain stem and spinal cord. Although it is
      well known that various central nervous system disorders can produce a 'pseudo
      infarction' pattern on the electrocardiogram, there have been no reports of this
      particular pattern in ALS patients. This report concerns an ALS patient who
      presented with an ECG pattern of S-T elevation followed by biphasic T and
      inverted T without any detectable myocardial abnormality. Data from the present
      case suggest that this pattern may be an inherent characteristic of ALS.

PMID- 10894920
TI  - Increased urinary cortisol and androgen metabolites in a young female with
      hypertension: partial glucocorticoid resistance syndrome.
AB  - A 21-year-old woman with hypertension confirmed on ambulatory blood pressure
      monitoring and unresponsive to beta-blockers, diltiazem and amiloride was found
      to have serum potassium, renin and aldosterone levels at or just below the lower
      end of normal. Urinary glucocorticoid metabolite analysis revealed high excretion
      of cortisol and androgen metabolites, with normal serum cortisol levels. This
      pattern suggests a partial glucocorticoid resistance syndrome; such patients are
      more responsive to ACE inhibitors and spironolactone.

PMID- 10894922
TI  - Assignment of the human PHLDA1 gene to chromosome 12q15 by radiation hybrid
      mapping.

PMID- 10894923
TI  - Chromosomal localization of GPR48, a novel glycoprotein hormone receptor like
      GPCR, in human and mouse with radiation hybrid and interspecific backcross
      mapping.
AB  - We report the chromosomal localization in both mouse and human of a novel G
      protein-coupled receptor, GPR48, which resembles glycoprotein hormone receptors,
      that may be implicated in Wilms tumor deletion syndromes such as WAGR. This
      receptor forms a novel sub-family of glycoprotein hormone-like GPCRs. We have
      mapped this receptor to human chromosome 11p14-->p13 by several approaches,
      including radiation hybrid and interspecific backcross mapping, and show that
      GPR48 is close to BDNF. This data differs from the recently published mapping of
      LGR4 (5q34-->q35.1) (Hsu et al., 1998). Additionally, we show that Gpr48 and Bdnf
      are tightly linked on mouse chromosome 2, in a region with conserved synteny to
      human 11p14-->p13.

PMID- 10894924
TI  - Assignment of human 3-phosphoglycerate dehydrogenase (PHGDH) to human chromosome
      band 1p12 by fluorescence in situ hybridization.

PMID- 10894925
TI  - Assignment of human xylosylprotein beta-1,4-galactosyltransferase gene (B4GALT7)
      to human chromosome 5q35.2-->q35.3 by in situ hybridization.

PMID- 10894926
TI  - Assignment of the endogenous retrovirus HERV-R (ERV3) to human chromosome 7q11.2
      by radiation hybrid mapping.

PMID- 10894927
TI  - Assignment of NUFIP1 (nuclear FMRP interacting protein 1) gene to chromosome
      13q14 and assignment of a pseudogene to chromosome 6q12.

PMID- 10894928
TI  - Assignment of the proline-rich protein gene Prp2 (alias D6Mit13) to mouse
      chromosome 6G1 by in situ hybridization.

PMID- 10894929
TI  - The Knsl1 gene encoding the kinesin-related protein MmEg5 maps to mouse
      chromosome 19 and a related pseudogene maps to mouse chromosome 6.

PMID- 10894930
TI  - The small GTPase RAC3 gene is located within chromosome band 17q25.3 outside and
      telomeric of a region commonly deleted in breast and ovarian tumours.
AB  - The closely related small GTP-binding proteins Rac1, Rac2, and Rac3 are part of a
      larger Rho subfamily of Ras proteins. Because disruption of Ras signaling
      pathways is relevant to the pathogenesis of a wide variety of cancers, it is
      important to clearly define the structural and functional characteristics of the
      participating proteins and their encoding genes. Rho subfamily members are
      involved in a range of signal transduction pathways relevant to cell growth,
      differentiation, motility, and stress, and Rac proteins are now recognised as a
      necessary component of Ras-mediated cellular transformation. We previously mapped
      RAC3 to chromosome band 17q23--> q25, a region that contains a number of
      candidate tumour suppressor genes. Because of its oncogenic potential, we have
      now further refined the location of this gene. Here we confirm that RAC3 maps to
      chromosome band 17q25.3 and further show that it maps some distance telomeric of
      a well-characterised minimal breast and ovarian candidate tumour suppressor gene
      region, BROV. The genomic structure of RAC3, including exon and intron
      boundaries, is also presented.

PMID- 10894931
TI  - Cloning of ZNF237, a novel member of the MYM gene family that maps to human
      chromosome 13q11-->q12.
AB  - We have cloned a novel, widely expressed human gene, ZNF237, that shows extensive
      similarity to the N-terminal region of ZNF198. Two alternatively spliced regions
      were identified by RT-PCR; the major splice variant is predicted to encode a 383
      amino acid protein that contains a single diverged MYM domain. ZNF237 maps to
      13q11-->q12, immediately proximal to ZNF198.

PMID- 10894932
TI  - An analysis of meiotic impairment and of sex chromosome associations throughout
      meiosis in XYY mice.
AB  - The existing XYY meiotic data for mice present a very heterogeneous picture with
      respect to the relative frequencies of different sex chromosome associations,
      both at pachytene and diakinesis/metaphase I. Furthermore, where both pachytene
      and diakinesis/MI data are available for the same males, the frequencies of the
      different configurations at the two stages are very different. In the present
      paper we utilise "XYY" and "XY/XYY" mosaic mice with cytologically
      distinguishable Y chromosomes to investigate the factors responsible for this
      heterogeneity between different males and between the two meiotic stages. It is
      concluded (1) that the initial pattern of synapsis is driven by the relatedness
      of the three pseudoautosomal regions (PARs); (2) that the order and extent of PAR
      synapsis within radial trivalents are also affected by PAR relatedness and that
      this leads to chiasmata being preferentially formed between closely related PARs;
      (3) that trivalents with a single chiasma resolve into a bivalent + univalent by
      the diakinesis stage; (4) that although many spermatocytes with asynapsed sex
      chromosomes are eliminated between pachytene and diakinesis, those that survive
      this phase of elimination progress to the first meiotic metaphase (MI) and
      accumulate in large numbers, leading to an over-representation of those with
      univalents as compared to radial trivalents; and (5) that the arrested MI cells
      are eventually eliminated, so that very few "XYY" cells contribute products to
      MII.

PMID- 10894933
TI  - Evidence that sex chromosome asynapsis, rather than excess Y gene dosage, is
      responsible for the meiotic impairment of XYY mice.
AB  - There is extensive evidence for the existence of a meiotic checkpoint that acts
      to eliminate spermatocytes that fail to achieve full sex chromosome synapsis at
      the pachytene stage of the first meiotic prophase. XYY mice are nearly always
      sterile, with clear signs of meiotic impairment, and sex chromosome asynapsis has
      been proposed to underlie this impairment. However, a study of XYY*(X) mice (mice
      having three sex chromosomes but only a single dose of Y genes) revealed that
      these mice are fertile, and thus implicated Y gene dosage as a major factor in
      the sterility of XYY mice. To address this question further, sex chromosome
      synapsis and spermatogenic proficiency were compared between XYY*(X) and XYY mice
      generated in the same litters. This established that differences in spermatogenic
      proficiency within and between the two genotypes correlated with the frequency of
      radial trivalent formation (full sex chromosome synapsis); XYY*(X) males, as a
      group, had double the radial trivalent frequency of XYY males. This observation
      provides strong support for the view that sex chromosome asynapsis (or some
      consequence thereof), rather than Y gene dosage, is the major factor leading to
      the meiotic impairment of XYY mice.

PMID- 10894934
TI  - Physical mapping of nine Xq translocation breakpoints and identification of
      XPNPEP2 as a premature ovarian failure candidate gene.
AB  - Women with balanced translocations between the long arm of the X chromosome (Xq)
      and an autosome frequently suffer premature ovarian failure (POF). Two "critical
      regions" for POF which extend from Xq13-->q22 and from Xq22-->q26 have been
      identified using cytogenetics. To gain insight into the mechanism(s) responsible
      for ovarian failure in women with X;autosome translocations, we have molecularly
      characterized the translocation breakpoints of nine X chromosomes. We mapped the
      breakpoints using somatic cell hybrids retaining the derivative autosome and
      densely spaced markers from the X-chromosome physical map. One of the POF
      associated breakpoints in a critical region (Xq25) mapped to a sequenced PAC
      clone. The translocation disrupts XPNPEP2, which encodes an Xaa-Pro
      aminopeptidase that hydrolyzes N-terminal Xaa-Pro bonds. XPNPEP2 mRNA was
      detected in fibroblasts that carry the translocation, suggesting that this gene
      at least partially escapes X inactivation. Although the physiologic substrates
      for the enzyme are not known, XPNPEP2 is a candidate gene for POF. Our breakpoint
      mapping data will help to identify additional candidate POF genes and to
      delineate the Xq POF critical region(s).

PMID- 10894935
TI  - Assignment of the kinin receptor B1 and B2 genes (Bdkrb1 and Bdkrb2) to rat
      chromosome 6q3.2 by FISH and radiation hybrid mapping.

PMID- 10894936
TI  - Assignment of the human RhoHP1 gene (ARHD) to chromosome 11q14.3 by radiation
      hybrid mapping.

PMID- 10894937
TI  - Assignment of the mitochondrial aldehyde dehydrogenase gene (Aldh2) to mouse
      chromosome 5 by fluorescence in situ hybridization.

PMID- 10894938
TI  - Chromosome mapping of RNF16 and rnf16, human, mouse and rat genes coding for
      testis RING finger protein (terf), a member of the RING finger family.
AB  - RNF16 (ring finger protein 16; alias terf), a member of the RING finger family,
      has been shown to be exclusively expressed in the testis. Human RNF16 is located
      at 1q42 based on PCR-assisted analysis of both a human/rodent mono-chromosomal
      hybrid cell panel and a radiation hybrid-mapping panel. On the other hand,
      chromosomal mapping of the RNF16 gene by fluorescence in situ hybridization
      reveals that mouse Rnf16 is located at 11B1.2-B1.3 and rat Rnf16 at 10q22. These
      results provide additional evidence that the mouse 11B region displays conserved
      linkage homology with the rat 10q22 region, whereas in the case of RNF16, this
      homology is only conserved among rodents, distinct from the 1q42 region of the
      human genome.

PMID- 10894939
TI  - Cloning, structural organization, and chromosomal assignment of the porcine c-fos
      proto-oncogene, FOS.
AB  - The complete porcine c-fos proto-oncogene (FOS) with flanking regions was cloned
      and sequenced. FOS consists of four exons at amino acids 1-47, 48-131, 132-167,
      and 168-380 and includes all the typical motifs of the fos proto-oncogene. The
      promoter contains consensus sequences for CRE, SRE, CaRE, and the E-Box, as well
      as an AP-1 site. Homologies between human and swine were between 89.7% and 96.3%
      in the exons. Based on somatic cell hybrid panel screening and known homologies
      between swine chromosome 7 and human chromosome 14, the porcine c-fos gene was
      assigned to chromosome 7q23.

PMID- 10894940
TI  - Fine mapping of the human preprocortistatin gene (CORT) to neuroblastoma
      consensus deletion region 1p36.3-->p36.2, but absence of mutations in primary
      tumors.
AB  - The processed product of the human gene preprocortistatin, the peptide
      cortistatin-17 (hCST-17), bears a strong structural resemblance to the peptide
      somatostatin (SST), which has an identical receptor binding domain. CST has
      affinity to all known SST receptor (SSTR) subtypes. Expression of both SST and
      its receptors has been shown in previous studies to have biological and clinical
      significance in neuroblastomas, with a putative role in tumor differentiation and
      apoptosis in vivo. In this work we have employed radiation hybrid mapping and BAC
      physical mapping to map the human preprocortistatin gene (CORT) to chromosome
      region 1p36.3-->p36.2, close to the genetic marker D1S244. D1S244 defines the
      centromeric border of the smallest region of overlap of deletion in our primary
      neuroblastoma material. We have also defined the genomic sequence of the gene by
      BAC sequencing and found that preprocortistatin consists of two exons divided by
      a 1-kb intron. Two polymorphic sites, neither of which causes amino acid
      exchange, have been detected in the coding region of the gene. Expression studies
      showed that preprocortistatin is expressed in neuroblastomas of all different
      stages, as well as in ganglioneuromas. Through genomic sequencing we made
      mutation analyses of exonic sequences in 49 primary neuroblastomas of all
      different stages, but no mutations could be detected.

PMID- 10894941
TI  - Conserved synteny between the chicken Z sex chromosome and human chromosome 9
      includes the male regulatory gene DMRT1: a comparative (re)view on avian sex
      determination.
AB  - Sex-determination mechanisms in birds and mammals evolved independently for more
      than 300 million years. Unlike mammals, sex determination in birds operates
      through a ZZ/ZW sex chromosome system, in which the female is the heterogametic
      sex. However, the molecular mechanism remains to be elucidated. Comparative gene
      mapping revealed that several genes on human chromosome 9 (HSA 9) have homologs
      on the chicken Z chromosome (GGA Z), indicating the common ancestry of large
      parts of GGA Z and HSA 9. Based on chromosome homology maps, we isolated a Z
      linked chicken ortholog of DMRT1, which has been implicated in XY sex reversal in
      humans. Its location on the avian Z and within the sex-reversal region on HSA 9p
      suggests that DMRT1 represents an ancestral dosage-sensitive gene for vertebrate
      sex-determination. Z dosage may be crucial for male sexual
      differentiation/determination in birds.

PMID- 10894942
TI  - DRM/GREMLIN (CKTSF1B1) maps to human chromosome 15 and is highly expressed in
      adult and fetal brain.
AB  - We have mapped and characterized the human homolog of Drm/Gremlin (CKTFS1B1), a
      member of a family of BMP antagonists that have been linked to both developmental
      and transformation-related functions. By screening a human cDNA library, we
      isolated a 3.3-kb cDNA containing the 552-bp region encoding the human DRM
      protein. CKTFS1B1 was localized on human chromosome 15q13--> q15 by somatic cell
      hybrid analysis and, more precisely, using radiation hybrids, to a region of
      markers linked to SGNE1, secretory granule neuroendocrine protein 1 and RYR3, the
      ryanodyne receptor 3. Northern blot analysis showed the presence of a single DRM
      specific mRNA expressed in different human tissues, including brain, ovary,
      intestine and colon. In the brain, DRM expression is associated with the region
      localized around the internal capsule in the large subcortical nuclei. DRM
      appears to be predominantly expressed in normal cells and tissues, including
      normal neurons, astrocytes and fibroblasts. Interestingly, we detected DRM
      expression in normal cells obtained from several patients, but not in tumor cell
      lines established from the same patients. The data suggest that down-regulation
      of DRM is associated with tumor progression, and support the hypothesis that
      human DRM may play an important role during both neuroembryological development
      and carcinogenesis.

PMID- 10894943
TI  - Genomic sequencing reveals the structure of the Kcnk6 and map3k11 genes and their
      close vicinity to the sipa1 gene on mouse chromosome 19.
AB  - In this report we present the analysis of two overlapping mouse cosmid clones
      that contain the entire Kcnk6, Map3k11 and Pcnxl3 genes, as well as part of the
      Sipa1 gene. The sequence and genomic organisation of the Kcnk6 and Map3k11 genes
      are described in detail. Sipa1 and Map3k11, which have independently been mapped
      with low resolution to the centromeric region of mouse chromosome 19, are shown
      here to lie close to each other and to the Kcnk6 gene, which has not previously
      been mapped. This gene cluster maps to the vicinity of the Dancer (Dc) mutation,
      which involves inner ear abnormalities and circling phenotypes. Since potassium
      channels have been implicated in deafness disorders, we have analysed the Kcnk6
      gene, which encodes a two-P domain potassium channel, in the Dc mutant. No Dc
      causing mutation in the Kcnk6 coding region could be identified. However, we
      detected a polymorphism in the Kcnk6 gene that leads to a C-terminal extension of
      the encoded protein by eight amino acids.

PMID- 10894944
TI  - Molecular cloning and characterization of a mouse homolog of human TNFSF14, a
      member of the TNF superfamily.
AB  - A member of the tumor necrosis factor (TNF) superfamily, human TNFSF14
      (hTNFSF14)/HVEM-L (herpes virus entry mediator ligand) was isolated as a cellular
      ligand for HVEM/TR2 and human lymphotoxin beta receptor (LTbetaR). TNFSF14
      induces apoptosis and suppresses tumor formation. We have isolated a cDNA clone
      for a mouse homologue of hTNFSF14 by signal sequence trap (SST) screening which
      we recently developed. The deduced amino acid sequence of the mouse TNFSF14
      (mTNFSF14) cDNA comprised 239 amino acid residues and was 77% identical to the
      hTNFSF14 protein. In Northern blot analysis, 2.1 kb and 4.2kb mTNFSF14
      transcripts were detected in spleen and lung, and in heart, respectively.
      Fluorescence in situ hybridization analysis localized the mTNFSF14 gene Tnfsf14
      to chromosome 17 which is tightly linked with Tnf, Lta, and Ltb.

PMID- 10894945
TI  - Cloning, mapping and expression analysis of VPS33B, the human orthologue of rat
      Vps33b.
AB  - We have identified VPS33B, the human ortholog of rat Vps33b. VPS33B encodes a
      transcript of 2482 nt with an ORF of 617 amino acids and a predicted protein size
      of 70.6 kDa. VPS33B contains a Sec-1 domain shared with a family of proteins
      involved in protein sorting and vesicular trafficking. Enriched expression of
      VPS33B was observed in testis. VPS33B was positioned at chromosome 15q26.1 by
      radiation hybrid mapping.

PMID- 10894946
TI  - Assignment of crystallin beta-polypeptide 1 (CRYBA1) to Atlantic bottlenose
      dolphin chromosome band 16p11 by in situ hybridization.

PMID- 10894947
TI  - Genomic structures and sequences of two closely linked genes (AMT, TCTA) on dog
      chromosome 20q15.1-->q15.2.
AB  - Analysis of genomic sequence from canine chromosome 20q15.1-->q15.2 revealed the
      presence of two closely linked genes. The two genes represent the corresponding
      canine orthologs of human aminomethyltransferase (AMT) and the human T-cell
      leukemia translocation associated (TCTA) gene. Aminomethyltransferase or glycine
      cleavage system T-protein is an important enzyme in glycine metabolism. The
      reported canine AMT gene spans 5 kb and consists of nine exons. It encodes a
      protein of 403 amino acids with 88% identity to human aminomethyltransferase.
      Human TCTA is located on 3p21 near the breakpoint of a t(1;3) translocation
      observed in some cancer cell lines. The 4-kb canine TCTA gene consists of three
      exons and probably represents a pseudogene. It is located adjacent to AMT and
      very close to DAG1 and BSN.

PMID- 10894948
TI  - Comparison of genomic structures of four members of beta-galactoside alpha2,3
      sialyltransferase genes in the mouse.
AB  - The mouse genes encoding beta-galactoside alpha2, 3-sialyltransferases-Siat4
      (ST3Gal I), Siat5 (ST3Gal II), Siat3 (ST3Gal III), and Siat4c (ST3Gal IV)-were
      isolated and characterized. Siat4 and Siat5 comprise 8.4 and 14 kb, respectively,
      and are composed of six exons each. The genomic structures of the two genes were
      similar. Siat3 and Siat4c comprise over 100 and 9.7 kb, respectively, and are
      composed of 12 and 10 exons, respectively. Although the genomic sizes of these
      genes differ, some of their exon structures are significantly similar. These
      results suggest that the gene pair Siat4 and Siat5 arose from a common ancestral
      gene, as did the two genes Siat3 and Siat4c.

PMID- 10894949
TI  - Assignment of the rabbit whey acidic protein gene (WAP) to rabbit chromosome 10
      by in situ hybridization and description of a large region surrounding this gene.

PMID- 10894950
TI  - Comparative cytogenetics of tapirs, genus tapirus (Perissodactyla, tapiridae).
AB  - Chromosomes of the four species of Tapirus were 2n = 52 in T. indicus, 2n = 76 in
      T. pinchaque, 2n = 80 in T. bairdii, and 2n = 80 in T. terrestris. The number of
      autosomal arms was 80-94. G-banded karyotypes indicated that a heterochromatic
      addition/deletion distinguished chromosomes 2 and 3 of T. bairdii and T.
      pinchaque, respectively. There were at least 13 conserved autosomes between the
      karyotypes of T. bairdii and T. terrestris, and at least 15 were conserved
      between T. bairdii and T. pinchaque. In G- and C-banded preparations, the X
      chromosomes of T. bairdii, T. indicus, and T. terrestris were identical, whereas
      the X chromosome of T. pinchaque differed from the X of the other species by a
      heterochromatic addition/deletion. The Y chromosome was a medium-sized to small
      acrocentric in T. bairdii, T. indicus, and T. pinchaque, but it was not
      positively identified in T. terrestris. There appeared to be fewer homologies
      between T. indicus and the three species occurring in Central and South America.
      Future cytogenetic studies of tapirs from the entire range of each of the four
      species might provide additional insight into their evolutionary biology and aid
      wildlife conservation efforts aimed at these threatened mammals.

PMID- 10894951
TI  - Assignment of ubiquilin2 (UBQLN2) to human chromosome xp11. 23-->p11.1 by
      GeneBridge radiation hybrids.

PMID- 10894952
TI  - Histone macroH2A1.2 is concentrated in the XY compartment of mammalian male
      meiotic nuclei.
AB  - We show here that histone macroH2A1.2 concentrates at the transcriptionally
      silent XY body, normally being formed during male meiosis in the mouse. A similar
      accumulation has earlier been observed on the inactive X chromosomes of somatic
      adult female mammalian cells by Costanzi and Pehrson (1998). This correspondence
      in the nature of heterochromatinization of the X chromosomes in males and females
      adds another property of X chromosome inactivation that is shared by males and
      females at different phases of their life cycle.

PMID- 10894953
TI  - DNA hypomethylation and unusual chromosome instability in cell lines from ICF
      syndrome patients.
AB  - The ICF syndrome (immunodeficiency, centromeric region instability, facial
      anomalies) is a unique DNA methylation deficiency disease diagnosed by an
      extraordinary collection of chromosomal anomalies specifically in the vicinity of
      the centromeres of chromosomes 1 and 16 (Chr1 and Chr16) in mitogen-stimulated
      lymphocytes. These aberrations include decondensation of centromere-adjacent (qh)
      heterochromatin, multiradial chromosomes with up to 12 arms, and whole-arm
      deletions. We demonstrate that lymphoblastoid cell lines from two ICF patients
      exhibit these Chr1 and Chr16 anomalies in 61% of the cells and continuously
      generate 1qh or 16qh breaks. No other consistent chromosomal abnormality was seen
      except for various telomeric associations, which had not been previously noted in
      ICF cells. Surprisingly, multiradials composed of arms of both Chr1 and Chr16
      were favored over homologous associations and cells containing multiradials with
      3 or >4 arms almost always displayed losses or gains of Chr1 or Chr16 arms from
      the metaphase. Our results suggest that decondensation of 1qh and 16qh often
      leads to unresolved Holliday junctions, chromosome breakage, arm missegregation,
      and the formation of multiradials that may yield more stable chromosomal
      abnormalities, such as translocations. These cell lines maintained the abnormal
      hypomethylation in 1qh and 16qh seen in ICF tissues. The ICF-specific
      hypomethylation occurs in only a small percentage of the genome, e.g., ICF brain
      DNA had 7% less 5-methylcytosine than normal brain DNA. The ICF lymphoblastoid
      cell lines, therefore, retain not only the ICF-specific pattern of chromosome
      rearrangements, but also of targeted DNA hypomethylation. This hypomethylation of
      heterochromatic DNA sequences is seen in many cancers and may predispose to
      chromosome rearrangements in cancer as well as in ICF.

PMID- 10894954
TI  - Genomic structure and chromosome location of the mouse RelA p65 gene (Rela).
AB  - The RelA (p65) subunit of transcription factor NF-kappaB plays a critical role in
      development, and rela(-/-) knockout mice die in utero from massive liver
      apoptosis. Only partial sequences of the mouse Rela gene are available. We have
      determined the genomic structure of mouse Rela and promoter, and have mapped the
      gene to chromosome 19B1-3.

PMID- 10894955
TI  - Genomic localization of the human genes TAF1A, TAF1B and TAF1C, encoding
      TAF(I)48, TAF(I)63 and TAF(I)110 subunits of class I general transcription
      initiation factor SL1.
AB  - Human SL1 is a general transcription initiation factor (GTF) essential for RNA
      polymerase I to start rRNA synthesis at class I promoters. It is comprised of the
      TATA box-binding protein (TBP) and three TBP-associated factors (TAF(I)48,
      TAF(I)63 and TAF(I)110). We have determined that the human genes TAF1A, TAF1B and
      TAF1C, encoding these three TAF(I) polypeptides, are localized at lq42, 2p25 and
      16q24, respectively. All three genes are present as single copies in the human
      genome and map to different chromosomes, as shown by somatic cell hybrid panel
      and radiation hybrid panel analysis and FISH. Two of these genes, TAF1C and
      TAF1B, are transcribed into multiple RNAs, as determined through Northern
      analysis of mRNA from various human organs and cell lines. If translated into
      different polypeptides, this could result in production of variant isoforms of
      SL1 with different activation potentials.

PMID- 10894956
TI  - Genomic organization of the human ubiquitin-conjugating enzyme gene, UBE2L6 on
      chromosome 11q12.
AB  - The human UBE2L6 gene encodes UbcH8(Kumar), a ubiquitin-conjugating enzyme (E2)
      highly simliar in primary structure to UbcH7 which is encoded by UBE2L3. Like
      UBC4 and UBC5 in yeast, these proteins demonstrate functional redundancy. Herein
      we report the intron/exon structure of UBE2L6. Comparison of the genomic
      organization of UBE2L6 with UBE2L3 demonstrates that these genes remain highly
      conserved at the genomic as well as at the protein level. We also describe the
      chromosomal localization of UBE2L6, which maps to chromosome 11q12.

PMID- 10894957
TI  - Revival of the use of botulinum toxin: application in dermatology.
AB  - Botulinum toxins (BTXs) comprise a family of neurotoxins designated as types A-G,
      which are produced by the anerobic bacterium Clostridium botulinum. BTX-A blocks
      the cholinergic transmission resulting in flaccid paralysis and autonomous nerve
      dysfunction. It has become a powerful therapeutic tool in a variety of conditions
      over the last decades. Primarily used in the treatment of strabismus,
      blepharospasm and hemifacial spasms, BTX has only recently been recognized in
      dermatology. The use of BTX in dermatology includes the treatment of focal
      hyperhidrosis, hyperfunctional facial lines as well as paralysis of the anal
      sphincter in the therapy of anal fissures. The mechanism of action is described
      and the current literature is reviewed.

PMID- 10894958
TI  - Patient compliance and disease management in the treatment of psoriasis in the
      Netherlands.
AB  - BACKGROUND: Compliance behaviour and disease management are important issues in
      chronic skin diseases. Psoriasis patients are 'experts by experience' because of
      many years of treatment. Therefore, it is relevant to gather data from patients
      on the actual use of antipsoriatic treatments. OBJECTIVE: The following questions
      are addressed: (1) What is the present mode of prescription and actual use of
      antipsoriatic treatments, including topical treatments, photo(chemo)therapy and
      systemic treatments? (2) What information do patients expect from their doctor,
      and do they actually receive this information. METHODS: To answer these
      questions, a questionnaire survey was mailed to the subscribers of Psoriasis, the
      journal of the Dutch Psoriasis Patients' Organisation. RESULTS: (1) Major issues
      in the treatment of psoriasis are (a) long-term management, (b) control of mild,
      moderate but also extensive psoriasis and (c) control of psoriasis on difficult
      localisations. Patients perceive itch, scaliness and visibility as major criteria
      for efficacy. (2) Topical treatment is the mainstay in the management of
      psoriasis. Calcipotriol is the most prescribed drug. Photo(chemo)therapy has an
      intermediate position between topical and systemic treatments. UVB is prescribed
      more than twice as frequently as PUVA and 10% of the patients on
      photo(chemo)therapy proved to be treated with UVB at home. Only 16% of the
      patients were on a systemic treatment; methotrexate and acitretin were the most
      frequently used systemic treatments. (3) More than 70% of the patients indicated
      that they had taken part in the selection of a treatment. In general, the
      patients were satisfied about the contact with their dermatologist and general
      practitioner. Compliance with the duration of treatment is limited, especially
      with regard to topical treatment. Patient compliance with the dose of the
      treatment is better. Again compliance is the worst in topical treatments. (4)
      Patients have a strong preference for an effective treatment which is safe for
      long-term use. Only a minority of patients wants a fast clearing treatment.
      CONCLUSION: Itch, scaliness and visibility provide the most relevant information
      on the severity of psoriasis, as the patients perceive themselves. Treatment
      duration is often unrestricted, especially with regard to topical treatments,
      which implies that the cumulative toxicity potential of these treatments may have
      a serious impact on their safety profile. Patients regard it of importance to
      have a vote in the selection of the treatment and regard safety as more important
      than fast clearing.

PMID- 10894959
TI  - Multiple familial basal cell carcinomas including a case of segmental
      manifestation.
AB  - BACKGROUND: A tendency to develop multiple basal cell carcinomas at an early age
      is a characteristic feature of some rare hereditary disorders; moreover, multiple
      basal cell carcinomas are sometimes observed as a corollary of familial basaloid
      follicular hamartomas or familial multiple trichoepitheliomas. OBSERVATION: We
      report 3 cases of multiple basal cell carcinomas involving 3 successive
      generations of a family, with a segmental manifestation of lesions in one of
      these patients. No additional cutaneous or extracutaneous anomalies were found.
      CONCLUSIONS: We hypothesize that a gene mutation may have caused the tumors
      observed in this family as an autosomal dominant trait. The segmental arrangement
      of tumors may reflect loss of heterozygosity: at an early stage of embryogenesis,
      a postzygotic mutation would give rise to a population of cells either homozygous
      or hemizygous for the underlying gene. The segmental arrangement following the
      lines of Blaschko would visualize the dorsoventral proliferation of a cell clone
      characterized by loss of the corresponding normal allele.

PMID- 10894960
TI  - Age-related alterations of echogenicity in Japanese skin.
AB  - BACKGROUND: Ultrasonic methods are commonly used for the noninvasive measurement
      of skin thickness. The effects of ageing on the skin have been reported to differ
      between Asians and Caucasians. Therefore, it is possible that the echogenicity of
      the skin on ultrasonographic images reflects differences in the skin architecture
      and properties that may vary among races and environments. OBJECTIVE AND METHODS:
      Since there have been a few reports on ageing-related changes in ultrasonic
      echogenicity in Caucasian skin, but not in Asian skin, we evaluated age-related
      changes in the echogenicity of ultrasonographic images by the ultrasonic B mode
      at 3 sites on the face (forehead, eye corners, cheeks) considered as sun-exposed
      areas and on the ventral forearms considered as weakly sun-exposed areas in 130
      Japanese females aged from 18 to 83 years. The dermis was divided into 3 layers
      (upper, middle, lower), and echogenicity was evaluated in each area. RESULTS: No
      age-related change in echogenicity was observed in the entire dermis. When the
      dermis was divided into 3 layers (upper, middle and lower dermis), the
      echogenicity was decreased in the upper layer and increased in the lower layer
      with age in all skin areas tested. In contrast, there were no age-related changes
      of echogenicity in the middle dermis. CONCLUSION: These findings suggest that, as
      for Caucasians, echogenicity in the upper and lower dermis is a useful tool for
      evaluating skin ageing in the Japanese.

PMID- 10894961
TI  - Biophysical assessment of persistent effects of moisturizers after their daily
      applications: evaluation of corneotherapy.
AB  - BACKGROUND: Although effective moisturizers can improve xerotic skin changes
      immediately, their effects are only transient, because the materials applied to
      the stratum corneum (SC) are easily shed from the skin surface by the daily
      desquamation process. However, there are a few lines of clinical as well as
      experimental evidence suggesting that, once application of effective moisturizers
      is repeated daily, they may produce persistent effects without being influenced
      by the desquamation of the skin surface. If we can expect such pharmacological
      effects by simple repeated applications of moisturizers on the skin surface, it
      will provide a great motivation for the introduction of corneotherapy into the
      treatment of xerotic skin problems. OBJECTIVE: This study was designed not only
      to confirm the feasibility of corneotherapy but to propose a practical method to
      assess such long-lasting effects of moisturizers by using biophysical methods.
      METHODS: We conducted applications of various moisturizers twice daily to
      different areas of the flexor surface of the forearms for the initial 5 days of
      the first week. Thereafter, we performed biophysical measurements of the SC of
      these areas in the second week, namely 3, 5 and 7 days after their last
      applications. RESULTS: Daily repeated applications of moisturizers did not induce
      any change in the water barrier function of the SC or in the size of desquamating
      corneocytes, a parameter for turnover rate of the SC. However, they substantially
      increased high-frequency conductance, a parameter for the hydration state of the
      skin surface, for several days in both normal individuals and patients with
      atopic xerosis, although the lasting effects were shorter in the latter. The
      obtained data enabled us to rank the efficacy of moisturizers either according to
      the duration of the lasting effects or the magnitude of an increase in the
      hydration levels of the SC. CONCLUSION: The present results confirmed the
      feasibility of corneotherapy, in which even simple application of moisturizers
      targeted at the SC can produce unexpected persistent clinical effects after their
      repeated treatments. The method described in this study constitutes a practical
      assay system to evaluate the efficacy of topical agents used for dry skin
      problems objectively and quantitatively.

PMID- 10894962
TI  - Apoptosis in established and healing psoriasis.
AB  - BACKGROUND: Previous studies have described apoptosis in the stratum granulosum
      and in the stratum corneum, but not in the germinative compartment in normal
      skin. In psoriasis, an increased epidermal apoptosis has been observed in the
      differentiated compartment, suggesting that apoptosis has a key role in the
      pathogenesis of psoriasis, as a counteracting factor to the overproduction of
      cells. Little is known on apoptosis in the germinative compartment. METHODS:
      Apoptosis was studied on biopsies of normal skin, established lesions of
      psoriasis and PUVA-treated psoriasis using the transferase-mediated uridine nick
      end labelling method, which detects fragmented DNA, and electron microscopy.
      Counting of apoptotic cells was restricted to the germinative compartment as
      defined by Mib1 staining to evaluate the impact of cell loss on cell production
      and tissue architecture. RESULTS: The apoptotic index was 0.12% in normal
      epidermis, 0.035% in established psoriasis and 0.31% in regressive psoriasis.
      CONCLUSION: These results have three implications: (1) they show the
      physiological presence of apoptosis in the germinative compartment in normal
      epidermis; (2) they suggest that induction of apoptosis is involved in the
      regression of psoriatic hyperplasia after PUVA therapy; (3) the decrease of
      physiological apoptosis in the psoriatic lesion suggests that this phenomenon
      could play a role in the induction of psoriatic hyperplasia.

PMID- 10894963
TI  - Intralesional methotrexate as effective treatment in solitary giant
      keratoacanthoma of the lower lip.
AB  - When size and location of a keratoacanthoma along with patient-related factors
      argue against surgical treatment, intralesional methotrexate shows to be an
      effective, easy and inexpensive alternative. The case report presented validates
      this treatment modality.

PMID- 10894964
TI  - Anal verrucous carcinoma and penile condylomata acuminata.
AB  - A 50-year-old man presented with recurrent tumorous lesions on the penis and the
      anal region. The anal lesion was histologically diagnosed as verrucous carcinoma
      (VC) and the penile lesions were in line with condylomata acuminata. Samples
      taken from tumors of both sites were human papillomavirus (HPV) DNA positive. Two
      of them taken from the penis and the perianal region scored HPV DNA 6 positive by
      using polymerase chain reaction and the Southern blot method. Treatment of both
      VC and condylomata acuminata consisted in surgery and adjuvant immune therapy.
      Neither tumor recurrence nor metastases occurred up until 6 months after therapy.

PMID- 10894965
TI  - Three cases of pityriasis rubra pilaris successfully treated with cyclosporin A.
AB  - BACKGROUND: Pityriasis rubra pilaris (PRP) is reported to respond poorly to
      cyclosporin A (CsA). OBJECTIVE: We attempted to determine the efficacy of CsA in
      the treatment of classic adult-type PRP. METHODS: Three patients with classic
      adult-type PRP were treated with 5 mg/kg/day CsA. RESULTS: A sustained clinical
      response was achieved within 2-4 weeks of therapy. Relapses were noted when the
      CsA dose was decreased to 1.2 mg/kg/day. CONCLUSION: CsA should be considered in
      the treatment of classical adult-type PRP.

PMID- 10894966
TI  - Recurrent neutrophilic eccrine hidradenitis in an HIV-1-infected patient.
AB  - Most cases of neutrophilic eccrine hidradenitis (NEH) have been reported in
      patients receiving chemotherapy for acute myelogenous leukemia or other malignant
      diseases. We report the case of an HIV-1-infected patient who presented several
      and strikingly similar episodes of NEH without any medication as well as another
      one after the first course of chemotherapy for a B-cell non-Hodgkin's lymphoma.
      This case strengthens the hypothesis that NEH may occur in different situations,
      as reported for other neutrophilic dermatoses.

PMID- 10894967
TI  - Muir-Torre syndrome - treatment with isotretinoin and interferon alpha-2a can
      prevent tumour development.
AB  - Muir-Torre syndrome is a genodermatosis in which multiple internal malignancies
      are associated with cutaneous sebaceous tumours and kerato-acanthomas. A 57-year
      old man presented with multiple sebaceous tumours, kerato-acanthomas, verrucous
      carcinoma of the nose, renal cell and transitional cell carcinomas of the left
      kidney, adenoma of the colon and a positive family history of colon carcinoma. He
      was treated with interferon (IFN-alpha2a) s.c. 3 x 10(6) U three times a week
      along with 50 mg isotretinoin daily as well as topical isotretinoin gel. During a
      follow-up of 29 months, only 1 sebaceous skin tumour developed and was removed,
      whereas more than 30 such skin tumours had been surgically removed during the
      last 3 years. No evidence of internal tumour development or recurrence was found.
      The combination of IFN with retinoids seems to be of promise to prevent tumour
      development in Muir-Torre syndrome.

PMID- 10894968
TI  - Cetirizine for solar urticaria in the visible spectrum.

PMID- 10894969
TI  - Hypertrophic eccrine glands in eccrine angiomatous hamartoma produce gross cystic
      disease fluid protein 15.

PMID- 10894970
TI  - Progression of Meyerson's naevus to Sutton's naevus.

PMID- 10894971
TI  - Diluted steroid facial wet wraps for childhood atopic eczema.

PMID- 10894972
TI  - Long-standing oral aphthae - a clue to the diagnosis of coeliac disease.

PMID- 10894973
TI  - Three cases of cutaneous sarcoidosis: search for bacterial agent by the 16S RNA
      gene analysis and treatment with antibiotics.
AB  - BACKGROUND: The aetiology of sarcoidosis remains controversial. An infectious
      origin is often discussed, but only anti-inflammatory or immunosuppressive
      treatment is recommended. OBJECTIVES: To investigate the hypothesis of bacterial
      origin by treating cutaneous sarcoidosis with antibiotics. METHODS: Patients with
      chronic cutaneous sarcoidosis, unresponsive to the usual treatment and not
      requiring systemic corticotherapy, were given combined antibiotherapy for 6
      months. Search for bacterial DNA by amplification and sequencing of the 16S
      ribosomal RNA gene in skin biopsies of lesions before and after antibiotherapy
      was done. RESULTS: Three patients received a combined treatment with
      clarithromycin 1 g/day and ciprofloxacin 1 g/day. No clinical changes occurred in
      2 cases and transient worsening in 1. Amplification for bacterial DNA was
      positive in all skin biopsies. The sequencing of this DNA could not identify a
      unique bacterial species. CONCLUSION: No evident bacterial origin could be
      demonstrated; however, this approach should be extended to more patients.

PMID- 10894974
TI  - Topical colchicine therapy for actinic keratoses.
AB  - BACKGROUND: The beneficial effect of topical colchicine therapy for actinic
      keratoses has already been described in 1968. OBJECTIVE: To confirm that the
      application of a 1% colchicine gel is a safe and effective treatment for actinic
      keratoses. METHODS: Twenty patients were included in a double-blinded protocol.
      They all had actinic keratoses on the scalp, most of which had been previously
      treated with 5-fluorouracil or cryotherapy. Ten patients applied twice daily on
      the forehead a hydrophilic gel (placebo group), while the other 10 where treated
      with the same gel containing 1% of colchicine (colchicine group). Erythema and
      efficacy were evaluated at each control on days 7, 30 and 60, with repetitive
      blood tests to exclude a possible systemic absorption. RESULTS: A complete
      healing of the solar keratoses was observed in 7 out of the 10 patients treated
      with 1% colchicine gel; these showed no recurrence after 2 months of follow-up.
      Burning and itching occurred only in the colchicine group after 2 or 3 days of
      application, with an inflammatory reaction on the areas where the gel was
      applied, while pustules and crusts were located specifically on the actinic
      keratoses. Repeated blood controls showed that there was no systemic absorption.
      CONCLUSIONS: This double-blind placebo-controlled study confirms the activity of
      colchicine for the treatment of actinic keratosis. A comparison with other
      topical treatments in terms of efficacy and practicability is needed.

PMID- 10894975
TI  - Delayed generalized allergic reactions to corticosteroids.
AB  - A 37-year-old patient presented with a severe allergic local reaction upon
      inhalation of budesonide for asthma. Skin tests were positive for budesonide and
      amcinonide (group B) and elicited a strong local reaction and a disseminated
      macular exanthema. Corticosteroids from other groups were well tolerated. A 38
      year-old male patient had first an allergic contact dermatitis to topically
      applied prednisolone acetate and then a disseminated eczematous exanthema upon
      oral intake of prednisone. A delayed-type sensitization to corticosteroids from
      group A such as hydrocortisone, prednisone and tixocortol pivalate was
      identified. A detailed diagnosis in patients with allergic reactions to
      corticosteroids is crucial with regard to their use in emergency therapy.

PMID- 10894976
TI  - Primary cutaneous cryptococcosis in a patient with systemic immunosuppression
      after liver transplantation.
AB  - We report a 36-year-old woman who slowly developed an ulceration on the left
      thigh 2 years after transplantation for Budd-Chiari syndrome. At this time point,
      the patient was treated with prednisone, tacrolimus and azathioprine for
      immunosuppression and with phenprocoumon and low-dose aspirin for anticoagulation
      in the presence of polycythemia vera. A biopsy of the skin lesion was obtained
      and revealed encapsulated yeast that was identified by microbiological and
      serological methods as Cryptococcus neoformans serotype D. The patient had no
      signs of systemic infection and a therapy with fluconazole (200 mg/day) was
      started. The lesion healed within 8 weeks and fluconazole was stopped after 3
      months. Due to interactions between fluconazole, tacrolimus and phenprocoumon,
      the latter drugs were decreased to prevent toxicity. So far, 1 month after
      stopping fluconazole, no recurrence of skin lesions has been observed.

PMID- 10894977
TI  - Typical features of calciphylaxis in a patient with end-stage renal failure,
      diabetes mellitus and oral anticoagulation.
AB  - We report a multimorbid patient with end-stage renal failure showing a large
      necrosis and livedo racemosa on the right thigh. Histology revealed medial
      calcification of the small arteries typical of calciphylaxis. We found the
      typical features of the disease with different risk factors like elevated calcium
      phosphate product, diabetes mellitus and oral anticoagulation. On account of the
      location of the skin lesions, a bad prognosis was expected. In spite of
      therapeutical measures with lowering of the calcium and phosphate levels, the
      patient died 1 month after the diagnosis had been made.

PMID- 10894978
TI  - Silicone granuloma.
AB  - Since silicone has rapidly become one of the most commonly used prosthetic
      materials in the last 30 years in modern medicine, we have consequently been
      witnessing more silicone-related disease. Especially after silicone breast
      implantation, defects in the breast implant have led to serious complications,
      whereas complications of silicone prosthesis implantation in other body parts are
      less frequent. Here we present an unusual clinical presentation of a silicone
      granuloma in a patient with a 27-year history of a wide excision of a melanoma of
      the right lower extremity and subsequent soft-tissue reconstruction using a
      silicone device.

PMID- 10894979
TI  - Thromboangiitis obliterans: a rare cause of a reversible Raynaud's phenomenon.
AB  - A 25-year-old woman with progressive Raynaud's phenomenon and digital necrosis is
      presented. Systemic sclerosis and other connective tissue disorders as well as
      atherosclerosis and arterial emboli were excluded with appropriate laboratory
      examinations. Arteriography revealed multiple palmar and digital occlusions with
      corkscrew-shaped vessels. Based on these characteristic arteriographic and
      clinical findings, the diagnosis of thromboangiitis obliterans was finally
      retained. With intravenous perfusion of the prostacyclin analogue iloprost (2
      ng/kg/min, 6 h daily during 21 days), a complete healing of Raynaud's phenomenon
      and of the digital necrosis was observed. There was no recurrence during the 1
      year follow-up. This observation demonstrates that thromboangiitis obliterans is
      a potential reversible cause of severe Raynaud's phenomenon in young women even
      in the absence of lower limb involvement. Early recognition is important to avoid
      irreversible complications such as loss of digits.

PMID- 10894980
TI  - Bullosis diabeticorum in a newly discovered type 2 diabetes mellitus.
AB  - Bullosis diabeticorum (BD), although a rare manifestation, is characteristic of
      diabetes mellitus. The exact origin of BD is unknown. We report another case of a
      54-year-old man who developed a blistering lesion on his left leg.
      Histopathological examination revealed a microangiopathy with hyalinosis of the
      blood vessel walls.

PMID- 10894981
TI  - A growing brownish macule on the sole of a doctor's spouse.

PMID- 10894982
TI  - Chick homeobox gene cDlx expression demarcates the forebrain anlage, indicating
      the onset of forebrain regional specification at gastrulation.
AB  - Here we describe the isolation and characterization of a chick homeobox
      containing gene, cDlx, which shows greater than 85% homology to the homeodomain
      of other vertebrate Distal-less genes. Northern blot analysis and in situ
      hybridization studies reveal that cDlx expression is developmentally regulated
      and is tissue specific. In particular, the developmental expression pattern is
      characterized by an early appearance of cDlx transcript in the prospective
      forebrain region of gastrulating embryos. During neurulation, cDlx is
      consistently expressed in a spatially restricted domain in the presumptive
      ventral forebrain region of the neural plate that will give rise to the
      hypothalamus and the adenohypophysis. Our data support the notion that members of
      the Dlx gene family are part of a homeobox gene code in forebrain pattern
      formation and suggest that regional specification of the forebrain occurs at much
      earlier stages than previously thought. The homeobox gene cDlx may thus play a
      role in defining forebrain regional identity as early as gastrulation.

PMID- 10894983
TI  - Expression of Foxb1 reveals two strategies for the formation of nuclei in the
      developing ventral diencephalon.
AB  - Fork head b1 (Foxb1; also called Fkh5, HFH-e5.1, Mf3) is a winged helix
      transcription factor gene whose widespread early expression in the developing
      neural tube is soon restricted to the ventral and caudal diencephalon. During
      diencephalic neurogenesis, Foxb1 is expressed in one patch of neuroepithelium
      comprising a large mammillary portion and a smaller tuberal portion. The labeled
      cells coming from this patch contribute to nuclear formation by means of two
      different strategies: (1) caudally, the young neurons aggregate and settle
      immediately, giving rise to the nuclei of the mammillary body; (2) rostrally, the
      young neurons separate from the neuroepithelium forming a trail of cells which
      spans the mantle layer mediolaterally and which will give rise to two separate
      cell groups (the dorsal premammillary and part of the lateral hypothalamic area).
      Our results show the elaborate, regionalized histogenetic mechanisms necessary
      for the differentiation of the caudal diencephalon; moreover, they suggest that
      specifically labeled populations, arising from specifically labeled
      neuroepithelial patches and giving place to specific brain nuclei could be a
      common mechanism to build complex, nonlaminar regions of the forebrain.

PMID- 10894984
TI  - Sonic hedgehog-mediated ventralization disrupts formation of the midbrain
      hindbrain junction in the chick embryo.
AB  - The secreted signaling molecule Sonic hedgehog (Shh) plays critical roles in
      pattern formation of the vertebrate central nervous system. During neurulation,
      Shh is produced by the ventral midline mesoderm as well as by the ventral neural
      tube, and its activity is required for the determination of ventral
      characteristics along the anterior-posterior neuraxis. The morphological boundary
      between midbrain and hindbrain, the isthmus, is an important tissue organizer
      that regulates the development of both the midbrain and the anterior hindbrain.
      In this study, we report that retrovirus-mediated misexpression of Shh in the
      early chick neural tube disrupts formation of the boundary between the midbrain
      and the hindbrain, and causes a fusion of the bilateral cerebellum primordia.
      Dorsally expressed Shh signals induce ectopic transcription of its receptor Ptc1
      in the midbrain and the hindbrain. The expression of several genes (Noggin, Lmx1,
      BMP7) along the dorsal midline of the midbrain is abolished, and ventral or
      lateral markers (HNF3 beta, Ptc1, ELF1) are induced in the dorsal brain.
      Furthermore, the normally restricted expression of two genes (En1 and Pax2) in
      the mid/hindbrain junction region are expanded, reflecting the morphological
      defects. These results suggest that maintaining proper dorsal-ventral patterns of
      the neural tube is essential for normal development of the mid/hindbrain region.

PMID- 10894985
TI  - Timing and competence of neural crest formation.
AB  - Neural crest cells can be induced by an interaction between neural plate and
      ectoderm. To clarify the timing and nature of these inductive interactions, we
      have examined the time of competence of the neural plate to become neural crest
      as well as the time of neural fold specification. The neural plate is competent
      to respond to inductive interactions with the nonneural ectoderm for a limited
      period, rapidly losing its responsive ability after stage 10. In contrast,
      nonneural ectoderm from numerous stages retains the ability to induce neural
      crest cells from competent neural plate. When neural folds are explanted to test
      their ability to produce neural crest without further tissue interactions, we
      find that folds derived from all rostrocaudal levels of the open neural plate are
      already specified to express the neural crest marker Slug. However, additional
      signals may be required for maintenance of Slug expression, since the transcript
      is later down-regulated in vitro in the absence of tissue interactions. Taken
      together, these results suggest that there are multiple stages of neural crest
      induction. The earliest induction must have occurred by the end of gastrulation,
      since the newly formed neural fold population is already specified to form neural
      crest. However, isolated neural folds eventually down-regulate Slug, suggesting a
      second phase that maintains neural crest formation. Thus, induction of the neural
      crest may involve multiple and sustained tissue interactions.

PMID- 10894986
TI  - Axons crossing in the ventral commissure express L1 and GAD65 in the developing
      rat spinal cord.
AB  - The neural cell adhesion molecule, L1, is thought to play a critical role in the
      formation and fasciculation of axon tracts during development. In the chick, the
      L1 cell adhesion molecule is expressed on both ipsi- and contralateral portions
      of commissural axons and perturbation studies produced a defasciculation of the
      ipsilateral commissural fibers. Yet in the rat, L1 is reported along commissural
      axons only after they have reached the contralateral marginal zone. When this
      species variation was reexamined, L1 was found to be expressed on rat commissural
      axons in a pattern similar to that observed in the chick. In addition, L1 is
      detected along commissural axons as early as embryonic day 12 in rats and
      maintained on both the ipsi- and contralateral surfaces during embryonic
      development. Other molecular markers that identify commissural axons in rats are
      TAG-1 (transiently expressed axonal glycoprotein) and DCC (deleted in colorectal
      cancer), and thus the pattern of L1 staining was compared with that of these
      other members of the immunoglobulin superfamily. Commissural axons emerging from
      dorsally located neurons are identified with TAG-1 and DCC, whereas L1 is
      detected only on ventrally located commissural axons. The pattern of L1
      expression overlaps that of the more numerous laterally and ventromedially
      located GABAergic commissural axons. Furthermore, some of the GABAergic
      commissural axons express L1 on their surfaces. While commissural axons are often
      considered as a single population, differences in the combination of adhesion
      type molecules on their surfaces and in their neurotransmitter phenotypes may
      signify distinctive neuronal subgroups.

PMID- 10894987
TI  - Expression of EphA4, ephrin-A2 and ephrin-A5 during axon outgrowth to the
      hindlimb indicates potential roles in pathfinding.
AB  - During neural development, spinal motor axons extend in a precise manner from the
      ventral portion of the developing spinal cord to innervate muscle targets in the
      limb. Although classical studies in avians have characterized the cellular
      interactions that influence motor axon pathfinding to the limb, less is known
      about the molecular mechanisms that mediate this developmental event. Here, we
      examine the spatiotemporal distributions of the EphA4 receptor tyrosine kinase
      (RTK) and its cognate ligands, ephrin-A2 and ephrin-A5, on motor neurons, their
      axons and their pathways to the avian hindlimb to determine whether these
      molecules may influence axonal projections. The expression patterns of EphA4,
      ephrin-A2 and ephrin-A5 mRNAs and proteins are highly complex and appear to
      exhibit some overlap during motor axon outgrowth and pathfinding to the hindlimb,
      reminiscent of the co-expression of Eph RTKs and ephrins in the retinotectal
      system. EphA4, similar to the carbohydrate moiety polysialic acid, strikingly
      marks the main dorsal, but not ventral, nerve trunk after axon sorting at the
      limb plexus region. Our results suggest that EphA4 RTK and its ligands may
      influence axon fasciculation and the sorting of axons at the limb plexus,
      contributing to the correct dorsoventral organization of nerve branches in the
      hindlimb.

PMID- 10894988
TI  - Relationship between ischemia and neuropathy.
AB  - To evaluate what at present is known about the relationship between vascular
      diseases and the development of chronic polyneuropathy, the literature on
      ischemia and peripheral nerve damage was reviewed with emphasis on chronic
      ischemia.

PMID- 10894989
TI  - Changes in cerebral hemodynamics during simple partial motor seizures.
AB  - Changes in cerebral perfusion were studied during nine short-lasting simple
      partial motor seizures (SPS) in an 11-year-old girl. Blood flow velocity changes
      in both middle cerebral arteries (MCAs) were assessed by transcranial Doppler
      sonography during simultaneous EEG monitoring. Within 7.4 +/- 1.4 s after
      electroencephalographic seizure onset, flow velocity in the MCA ipsilateral to
      the electrical discharges started to increase and then gradually rose up to 70%
      above baseline values. Spread of the epileptic activity to the other hemisphere
      in the late stage of seizure was associated with a slight increase in blood flow
      velocity (<30%) in the contralateral MCA. After the end of the seizure, flow
      velocities returned to baseline within 47 +/- 7 s. Our findings indicate that
      focal epileptic seizures evoke asymmetric perfusion increases which are closely
      related to the onset and cessation of the electroencephalographic seizure
      activity.

PMID- 10894990
TI  - Contribution of PET studies in diagnosis of corticobasal degeneration.
AB  - Five patients with clinical features of corticobasal degeneration (CBD) were
      studied with PET imaging. The main clinical findings included a unilateral
      extrapyramidal motor disorder, without significant response to levodopa, as well
      as clumsiness, dysarthria, apraxia and a clear asymmetry of neurological signs.
      PET studies with (18)F-labeled 2-deoxy-2-fluoro-D-glucose disclosed mainly a
      significant hypometabolism in the thalamus and motor cortex controlateral to the
      more affected limbs. Additional relationships between individual clinical signs
      and PET data were also found. We concluded that PET findings supported the
      clinical diagnosis of CBD, although the specific pattern related to this
      condition needs to be more precisely defined. Further studies are especially
      needed to correlate clinical data and PET results with pathological examination.

PMID- 10894991
TI  - Five-year follow-up of early lisuride and levodopa combination therapy versus
      levodopa monotherapy in de novo Parkinson's disease. The French Lisuride Study
      Group.
AB  - The value of an early initial coadministration of levodopa (L-dopa) and lisuride
      in Parkinson's disease was the main goal of the present study. Eighty-two
      patients with recently diagnosed idiopathic Parkinson's disease were randomized
      into two groups for treatment with L-dopa alone or L-dopa + lisuride. The trial
      was double-blinded for the first year and open for the following 4 years.
      Selegiline (10 mg/day b.i.d.) was added in both groups at the end of the first
      year. Outcome measures were evolution of L-dopa dosage and Unified Parkinson's
      Disease Rating Scale scores and subscores, and incidence of motor complications.
      The dropout rate was higher in the L-dopa group (63.4%) than in the combination
      group. Motor improvement was better (p < 0.01) in the L-dopa + lisuride group.
      Expected motor complications were rare, moderate and equivalent in the two groups
      despite a difference in L-dopa dosage (446.7 vs. 387.5 mg/day). Long-term follow
      up demonstrated the L-dopa-sparing effect of lisuride (average 1 mg/day), the
      beneficial effect of early combination therapy on motor status and the paucity of
      motor complications in both groups.

PMID- 10894992
TI  - Relative frequencies of CAG expansions in spinocerebellar ataxia and
      dentatorubropallidoluysian atrophy in 116 Italian families.
AB  - Two hundred and forty-eight patients from 116 Italian families with dominant
      ataxia were studied for CAG expansion within SCA1, 2, 3, 6, 7 (spinocerebellar
      ataxia) and DRPLA (dentatorubropallidoluysian atrophy) genes. Fifty-six percent
      of the families originated from Southern, 19% from Central and 25% from Northern
      Italy. SCA2 was the commonest mutation, accounting for 47% of the families,
      followed by SCA1 (24%), SCA6 (2%), SCA7 (2%) and DRPLA (1%). No SCA3 family was
      found. Twenty-four percent of the families carried a still unidentified mutation.
      When occurrence of mutations was evaluated according to the geographic origin,
      SCA1 was the commonest in Northern (72%), whereas SCA2 was prevalent (63%) in
      Southern Italy. The number of CAG repeats in SCA1 normal alleles was higher in
      Northern than in Central-Southern Italy.

PMID- 10894993
TI  - Complex mitochondriopathy associated with 4 mtDNA transitions.
AB  - In a 33-year-old man, mitochondriopathy was diagnosed upon short stature,
      auditory impairment, gynaecomastia, hypogonadism, vertical ophthalmoplegia,
      cerebral atrophy, leucencephalopathy, cataract, hypertrabeculated left ventricle,
      hypothyroidism, diabetes mellitus, glomerulonephritis necessitating kidney
      transplantation, general wasting, polyneuropathy, abnormally high lactate levels
      on exercise, partially reduced cytochrome-c oxidase staining and abnormally
      structured mitochondria on muscle biopsy. Mitochondrial DNA (mtDNA) analysis
      revealed 1 novel (A15662G) and 3 known mtDNA transition(s) (T3398C, T4216C,
      G15812A) affecting the cytb and ND1 gene, respectively. Three of the patient's
      transitions were also detected in blood leukocytes of the patient's maternal
      grandmother, mother and brother. Mutant mtDNA was heteroplasmic at >75% in the
      patient's skeletal muscle.

PMID- 10894994
TI  - Transient ischemic attack in heavy cannabis smokers--how 'safe' is it?
AB  - Drugs are lately considered high-risk factors for cerebrovascular disease. Three
      male patients (mean age 24.6 years) who were heavy cannabis smokers presented
      with transient ischemic attacks (TIA) shortly after cannabis abuse. The complete
      examination of all 3 consisted of: EEG, brain CT scan, brain MRI, cerebral vessel
      angiography (digital subtraction and magnetic resonance angiography); also a full
      cerebrospinal fluid, urine and blood analysis (immunological, biochemical and
      hormonal tests were included). Urine was further examined for drug metabolites.
      An extensive cardiological investigation was carried out. Small vessel
      leukoencephalopathy was revealed by the brain CT and MRI. EEG recordings of the
      first patient showed paroxysmal sharp waves with left hemispheric dominance. The
      other 2 patients had diffuse delta and theta activity in their EEG tracings. The
      urine analysis was positive for cannabis metabolites. There were no other
      abnormal findings in the rest of the meticulous and thorough study of all 3
      patients, which leads to the conclusion that cannabis was the only risk factor
      responsible for the observed TIA, contradictory to other studies, which support
      that cannabis is a 'safe' drug. More research is required in order for this issue
      to be completely elucidated.

PMID- 10894995
TI  - Low-dose gabapentin combined with either lamotrigine or carbamazepine can be
      useful therapies for trigeminal neuralgia in multiple sclerosis.
AB  - Paroxysmal symptoms occur frequently in multiple sclerosis (MS). Usually they are
      treated with carbamazepine (CBZ) and phenytoin, although these medications are
      often interrupted due to adverse effects. We report 11 MS patients with
      trigeminal neuralgia (TN): 6 intolerant to a therapeutic dosage of CBZ, showing
      serious adverse effects and subsequently treated with a combination of low-dose
      CBZ and gabapentin (GBP) (group 1); 5 treated with lamotrigine (LMT), showing
      adverse effects and subsequently treated with GBP (group 2). Subjective pain
      level and impairment in performing daily activities were rated utilizing a 3
      point scale at time 0 and at optimal dosage time (T1). GBP was initiated at 300
      mg daily and titrated, until pain control was achieved without new adverse
      effects, to a maximum dose of 1,200 mg daily. CBZ or LMT were reduced to a level
      which no longer produced adverse effects, although resulting in a lack of
      efficacy in relieving pain. Pain control was obtained in all patients but 1, with
      no side effects. The plasma level analysis, performed in 5 patients, resulted in
      normal values. The mean dosages at T1 were: group 1 CBZ 400 mg and GBP 850 mg
      daily; group 2 LMT 150 mg and GBP 780 mg daily. Combining drugs with
      complementary modes of action may provide a rational pharmacological approach to
      the management of TN in MS.

PMID- 10894997
TI  - Cognitive impairment in polycythemia vera: partial reversibility upon lowering of
      the hematocrit.

PMID- 10894996
TI  - Serum markers of type I collagen synthesis and degradation in amyotrophic lateral
      sclerosis.
AB  - Collagen abnormalities in the skin and spinal cord have been reported in
      amyotrophic lateral sclerosis (ALS) patients. Serum carboxyterminal propeptide of
      type I procollagen (PICP) and the carboxyterminal cross-linked telopeptide of
      type I collagen (ICTP) reflect type I collagen synthesis and degradation,
      respectively. However, there has been no study concerning PICP or ICTP in ALS. We
      studied collagen contents of the skin and measured serum levels of PICP and ICTP
      in patients with ALS and control subjects. Serum PICP levels were significantly
      lower in ALS patients than in controls. Serum ICTP levels were significantly
      higher in ALS patients than in controls, and there was an appreciable positive
      correlation between serum ICTP levels and the duration of illness in ALS
      patients. In ALS patients, the collagen content of the skin was significantly
      smaller than in controls and indicated a progressive decrease in relation to
      illness. In addition, there was a significant negative correlation between serum
      ICTP concentrations and the collagen content of the skin in ALS patients. These
      data suggest that increased ICTP levels and decreased serum PICP levels may
      reflect unique changes in the skin, with a predominance of degradation compared
      to the synthesis of type I collagen in ALS.

PMID- 10894998
TI  - Posterior thoracic spinal cord infarction: complication of thoracoabdominal
      aortic aneurysm.

PMID- 10894999
TI  - Severe X-linked Charcot-Marie-Tooth neuropathy due to new mutations [G59R(G-->C),
      W44X(G-->A)] in the connexin 32 gene.

PMID- 10895000
TI  - Ischemic stroke following cisplatin and 5-fluorouracil therapy: a transcranial
      Doppler study.

PMID- 10895001
TI  - Radical cystectomy for invasive bladder cancer: contemporary results and
      remaining controversies.
AB  - The impact of stage progression of superficial cancer to invasive disease is
      profound. However, the optimal-timed management of invasive bladder cancer is
      still controversial. Pelvic lymph node dissection and radical cystectomy are
      considered to be the optimal therapy regarding local tumor control and ultimate
      cure of cancer, whereas chemotherapy offers the only viable but limited option
      for patients with distant metastasis or locally advanced disease. Identification
      of conventional and molecular prognostic factors to predict cancer-specific
      survival following radical cystectomy is one important step to identify
      candidates that may benefit from early cystectomy or adjunct chemotherapy. With
      this background, the results of historic and contemporary radical cystectomy
      series for carcinoma of the bladder are reviewed.

PMID- 10895002
TI  - Laparoscopic surgery for stage T1 renal cell carcinoma: radical nephrectomy and
      wedge resection.
AB  - OBJECTIVES: Renal cell carcinoma (RCC) is likely to become one of the most
      important indications for laparoscopic surgery. We herein report our experience.
      METHODS: From April 1994 until April 1999, 98 patients presenting with RCC were
      treated laparoscopically by either radical nephrectomy (RN; n = 73) or wedge
      resection (WR; n = 25). The mean age was 62.3 years. The mean tumour diameters
      were 3.8 cm (RN) and 1.9 cm (WR). All tumours were clinical stage T1 lesions. The
      transperitoneal approach was used for RN in all patients. For WR either the
      transperitoneal or the retroperitoneal approach was used. In 15 patients, the
      adrenal gland was removed simultaneously. The specimen was entrapped in an organ
      bag and removed intact through a small muscle-splitting incision in the lower
      abdominal wall. RESULTS: RN: The mean operating time was 142 (range 86-230) min,
      the mean blood loss was 170 (range 0-1,500) ml, and the mean postoperative
      hospital stay was 7.4 (range 3-32) days. Minor complications occurred in 4.0% of
      the patients, while major complications were seen in 8.0% of them. WR: The mean
      operating time was 163.5 (range 90-300) min, the mean blood loss was 287 (range
      20-800) ml, and the postoperative hospital stay was 8.0 (range 3-8) days. Minor
      complications: 4%, major complications: 8%. Histology revealed RCC stage T1 in 77
      patients, stage T3a in 7, and stage T3b in 3 patients, oncocytoma in 2 patients,
      angiomyolipoma in 2, renal adenoma in 1, renal metastasis in 1, multilocular
      cysts in 4, and renal abscess in 1 patient. Over mean follow-up periods of 13.3
      and 22.2 months for RN and WR, respectively, neither local recurrences nor
      metastases have been observed among patients with histologically confirmed RCC.
      CONCLUSIONS: Laparoscopic surgery for clinical stage T1 RCC is safe and
      efficient. Excellent tumour control can be achieved. However, longer follow-up
      periods will be necessary to confirm these results.

PMID- 10895003
TI  - Ureteroscopic endopyelotomy with the Holmium:YAG laser. mid-term results.
AB  - OBJECTIVE: Various modalities ranging from acucise balloon to endoincision with
      electrocautery, cold knife, and lasers have been used to treat ureteropelvic
      junction obstruction (UPJO). We assessed the intermediate effectiveness of
      endopyelotomy with the holmium(Ho):YAG laser. PATIENTS AND METHODS: Between
      November 1994 and May 1998, 20 patients with 16 primary and 4 secondary
      symptomatic UPJO were treated. All patients were evaluated clinically and
      radiologically before and after the procedure at 3 months, and yearly thereafter.
      The mean follow-up was 34 months (12-38 months). RESULTS: A total of 22 procedure
      were performed on 20 patients with an average operating time of 44.3 min and mean
      hospital stay of 1.9 days. All patients were stented after the procedure for 6
      weeks. Complication included urinoma (1) and guidewire fracture in 1 patient. 15
      patients had a successful outcome determined by a diuretic renography and/or
      Whitaker test. Three patients with poor preoperative renal function (<25%) had an
      unsatisfactory outcome. There were 2 failures and they were treated with
      nephrectomy (1) and open pyeloplasty (1). CONCLUSIONS: A controlled, precise,
      safe and almost 'bloodless' endopyelotomy can be performed with the holmium
      laser. Success rate tends to be poor in patients with poor renal function.

PMID- 10895004
TI  - Encrustation of a metal alloy urinary stent: a mechanistic investigation.
AB  - MATERIALS AND METHODS: A section of a metal stent consisting mainly of tantalum
      coated partially by strongly adhering calcium oxalate monohydrate (COM) crystals
      was immersed in supersaturated solutions prepared from calcium chloride and
      sodium oxalate at 37 degrees C and ionic strength 0.15 M in NaCl. Abstract
      OBJECTIVES: To investigate the kinetics of encrustation of a metall alloy urinary
      stent system in vitro by calcium oxalate and characterize the crystals forming
      from solutions supersaturated with respect to all calcium oxalate hydrates.
      RESULTS: The COM-coated stent mineralized upon immersion in the supersaturated
      solutions. The process was monitored with a calcium ion-selective electrode and
      the rates were measured at conditions of sustained solution supersaturation. COM
      crystals formed on the stent and the rate of COM crystal growth yielded a second
      order dependence on the solution supersaturation. CONCLUSIONS: The deposition of
      COM crystals on the metal stents coated partially with COM crystals by adhesive
      forces was found to be most important for the acceleration of the encrustation
      process. The dependence of the rates on the solution supersaturation suggested
      absence of secondary nucleation and a surface-controlled process for the
      encrustation process.

PMID- 10895005
TI  - Tension-free vaginal mesh repair for anterior vaginal wall prolapse.
AB  - OBJECTIVES: We determined the efficacy of the use of a tension free prolene mesh
      to correct a grade III anterior vaginal wall prolapse recurrence. METHODS: Twelve
      women (mean age 65.6 years) with stress urinary incontinence (SUI) (4 type II and
      1 type III) and bladder prolapse entered the study. After vaginal incision a
      pretailored polypropylene mesh was fixed to its four angles by absorbable sutures
      to the urethropelvic ligaments and pubocervical fascia anteriorly and to the
      cardinal ligaments and pubocervical fascia posteriorly. When present, a posterior
      descensus was corrected during the same procedure. SUI was treated with the
      tension-free vaginal tape procedure (TVT) through a separate vaginal incision
      over the mid-urethra. RESULTS: All patients were available for postoperative
      pelvic examination at 3-month intervals, for a mean follow-up of 20.5 months
      (range 15-32). Nine patients were considered cured (no cystocele recurrence)
      while in 3 patients a grade 1 asymptomatic cystocele was present postoperatively
      (asymptomatic). No significant postoperative pain was reported by the patients.
      CONCLUSIONS: This study confirms that in patients with moderate cystocele a
      tension-free mesh to support bladder base and neck effectively treats the
      cystocele. It is particularly recommended in the treatment of previous failure
      with traditional techniques and when the quality of suspending tissue is poor or
      defective. A long-term study on a large number of patients is still warranted to
      confirm and validate its clinical use.

PMID- 10895006
TI  - The artificial urinary sphincter in 86 patients with intrinsic sphincter
      deficiency: satisfactory actuarial adequate function rates.
AB  - OBJECTIVE: To evaluate the long-term results of the AMS-800 artificial urinary
      sphincter (AUS) in patients with incontinence due to intrinsic sphincter
      deficiency, taking into account the continence status and the durability of the
      device. PATIENTS AND METHODS: Between 1984 and 1997, an AUS was implanted in 86
      patients. Kaplan-Meier survival analysis was used to determine the 'primary
      adequate function' rate (P-AF) and the 'additional procedure assisted adequate
      function' rate (APA-AF). These rates define adequate function as satisfactory
      continence (use of maximally 1 pad per 24 h) in combination with good AUS
      function. In the case of P-AF, no revisions have been required. In the case of
      APA-AF, one or more revisions of parts of the AUS are acceptable but a complete
      exchange or explantation of the AUS marks its endpoint. RESULTS: At last follow
      up, satisfactory continence was found in 76% of the patients. Continence was
      markedly improved in another 7%. The 5-year P-AF and APA-AF rates were 46 and
      67%, respectively. The 5-year P-AF rates for the periods before and after the
      introduction of the narrow backed cuff were 33 and 61%, respectively (p = 0.03).
      CONCLUSIONS: The AUS can give excellent results as far as urinary continence is
      concerned, but only at the expense of a considerable reoperation rate. The 5-year
      actuarial primary adequate function rate has almost doubled since the
      introduction of the narrow backed cuff design.

PMID- 10895007
TI  - Long-term follow-up of the in-flowtrade mark intraurethral insert for the
      treatment of women with voiding dysfunction.
AB  - OBJECTIVE: The aim of the current study is to report the long-term follow-up of
      women treated with the In-Flowtrade mark device for periods longer than 1 year.
      Abstract METHODS: The efficacy of the intraurethral insert was evaluated in 92
      women. Data regarding their urodynamic diagnosis, complications and satisfaction
      were collected. RESULTS: Early and late discontinuation of the device use was
      recorded in 52 patients (56.5%) and 19 patients (20.6%), respectively. Twenty-one
      patients (22.8%) are now being followed for more than 1 year with a follow-up
      time of 12-44 months (mean 24.6). Complications include device migration into the
      bladder (4 patients), asymptomatic bacteriuria (15 patients), and symptomatic
      urinary tract infections (4 cases, 1 of them pyelonephritis). In the 3 women who
      were sexually active before treatment, the use of the device did not preclude
      sexual intercourse, although mild dyspareunia was reported in 1 patient. Two
      patients complained of episodic inconvenience between their legs during walking.
      All patients were satisfied with the device and preferred it to previous
      treatment modalities used. The reasons for early and late discontinuation of
      treatment are described and discussed. CONCLUSIONS: The In-Flowtrade mark
      intraurethral insert can serve as a long-term treatment for the management of
      women with voiding difficulties. Women who continue treatment for a prolonged
      time are satisfied with the device use. Further studies comparing this treatment
      with other modalities are needed to support the role of the In-Flowtrade mark
      device in the management of women with voiding dysfunction.

PMID- 10895008
TI  - Congenital and acquired penile deviation treated with the essed plication method.
AB  - OBJECTIVES: To evaluate our results with the Essed procedure for the correction
      of penile curvature, either congenital or due to Peyronie's disease, and compare
      it with the data from the literature, both for the Essed and the Nesbit
      procedure. METHODS: From 1991 to 1996 the Essed procedure was performed in 61
      patients. 65.6% (n = 40) had congenital deviation and 34.4% (n = 21) suffered
      from secondary deviation due to Peyronie's disease. In all patients 2-6
      nonabsorbable inverting interrupted sutures were placed bringing the knot between
      the plicated tunica. RESULTS: Patients' ages ranged from 15 to 65 (mean 31.3)
      years and the mean follow-up time was 39.8 (12-75) months. The preoperative
      penile deviation was between 20 and 90 degrees (mean 47.4 degrees ). Eighteen
      patients (29.5%) had a recurrent deviation following surgery. This failure rate
      was higher in the patient group with Peyronie's disease (42.9%) than in the group
      with congenital deformation (22.5%). Postoperatively, 2 patients (3.3%) with
      Peyronie's disease reported de novo erectile dysfunction. Twenty patients (32.8%)
      complained of persistent discomfort or pain at the area of the still palpable
      plication sutures, but this inhibited sexual intercourse only in 1 case. 45.9%
      stated penile shortening after surgery but only 21.3% felt bothered by this.
      CONCLUSION: The results reported are in accordance with the literature showing a
      higher recurrence rate of the deviation with the Essed compared to the Nesbit
      procedure. For both methods the risk of recurrent disease is higher in patients
      with Peyronie's disease and with both techniques, an equally low incidence of
      erectile dysfunction is evident. However, since with the Essed technique one
      third of all patients complained of discomfort from the nonabsorbable sutures,
      the Nesbit procedure seems to be superior.

PMID- 10895009
TI  - Correction of complex penile deformities by modified nesbit procedure asymmetric
      tunica albuginea excision.
AB  - PURPOSE: Penile angulation combined with penile torsion is an uncommon finding in
      case of congenital or acquired penile curvature. We describe our technique for
      treatment of complex penile curvature by the excision of asymmetric ellipses of
      tunica albuginea. MATERIALS AND METHODS: During the last 4 years, 4 patients with
      complex penile curvature underwent surgical correction by the excision of
      asymmetric ellipses of tunica albuginea. 3 patients had Peyronie's disease and 1
      had congenital penile deviation. They ranged in age from 27 to 63 years. RESULTS:
      Convalescence was uneventful with good cosmetic correction of the penile torsion
      and lateral curvature in all patients. 1 patient reported shortening of the penis
      of about 2 cm, postoperatively. 2 patients reported decreased penile sensation,
      which resolved after 3 months. Erectile failure did not occur postoperatively in
      any case. CONCLUSIONS: During the last years many Authors have modified the
      original surgical procedure in an attempt to correct penile deformity.
      Unfortunately there are very few reports about correction of penile deformities
      combined with penile torsion. Our modified Nesbit surgical technique for complex
      deformities differs from the others with regard to the shape of the incision. In
      this manner, by shortening the longer corporeal body and creating a torque on the
      penis, it is possible to correct both problems: penile angulation and torsion.
      The technique is simple, bloodless, safe and reliable. In our experience good
      cosmetic and functional results have been achieved without complicated surgical
      interventions.

PMID- 10895010
TI  - Safety and efficacy of alprostadil sterile powder (S. Po., CAVERJECT) in diabetic
      patients with erectile dysfunction.
AB  - OBJECTIVES: To evaluate the long-term efficacy and safety of intracavernosal
      alprostadil (CAVERJECT((R))) in diabetic patients with erectile dysfunction (ED).
      PATIENTS AND METHODS: This study included 31 diabetic men (aged 44-75 years) with
      ED of >/=4 months duration. All patients were initially instructed in the self
      injection technique at the investigator's clinic. The optimal dose was determined
      for each patient and set at one of the following: 5, 10, 20, 30, 40, 50, or 60
      microg. After the optimal dose was determined and the patient was well trained,
      the self-injection home phase was followed for 6 months. The efficacy and adverse
      events were documented. RESULTS: An optimal dose was determined for 29 men
      (93.5%) and in 16 men (55%) it was >/=20 microg. During the home phase, 76.5% of
      injections assessed by the patients resulted in satisfactory sexual activity and
      72.5% of injections assessed by partners resulted in satisfactory intercourse. A
      total of 16 patients dropped out during the titration phase (n = 2) and the home
      phase (n = 14). The most common reasons included lack of efficacy (n = 3, all in
      the home phase), intolerable penile pain (1 in the titration phase, 2 in the home
      phase) and dissatisfaction with the higher dosage (n = 2). Penile pain occurred
      in 19 (61%) of 31 patients. Most were tolerable, and the incidence decreased with
      time. Prolonged erection occurred in 2 men (6.5%), and no priapism was noted.
      Penile fibrosis occurred in 1 patient (3. 2%). None of the systemic medical
      events were related to the study mediction. However, 1 patient suffered from
      right putaminal hemorrhage in the last month, and this was considered to be
      caused by underlying hypertension and not drug-related. CONCLUSION: Despite the
      high incidence of penile pain, most of the occurrences were tolerable. Despite a
      higher withdrawal rate in this study, intracavernosal alprostadil is still
      considered as a relatively effective and safe treatment in some diabetic patients
      with ED if the individual dose is established by titration and patients are
      trained in the self-injection technique with period supervision.

PMID- 10895011
TI  - Sildenafil in the treatment of sexual dysfunction in spinal cord-injured male
      patients.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of
      sildenafil in the treatment of erectile dysfunction (ED) in spinal cord-injury
      (SCI) patients. Moreover, we looked for neurological conditions permitting
      therapeutic success and for the ideal dose needed to achieve sufficient
      erections. METHODS: 41 SCI patients were prospectively examined. Sexual
      dysfunction was assessed by means of anamnesis, the International Index of
      Erectile Function (IIEF) questionnaire, and neurological examination. Psychogenic
      erection capacity was tested by audiovisual stimulation and reflexive erection
      using a vibrator device. Neurophysiological recordings and cystomanometry were
      performed in parallel to clinical examinations. Neurophysiological recordings
      included sympathetic skin responses (SSR), pudendus somatosensory evoked
      potentials (pSSEP), and bulbocavernous reflex (BCR). Urodynamics aimed at
      classifying the neurogenic bladder dysfunction (upper motoneuron lesion versus
      lower motoneuron lesion). Intracavernous injection tests with PGE1 were performed
      in all patients to exclude major organic disease. 50 mg sildenafil was first
      given 3 times. Thereafter, the doses were adapted according to patients' reports.
      RESULTS: Clinically, 28 subjects preserved either reflexive erections (24) or
      psychogenic erections (4), 11 had both types and only 2 presented with a complete
      loss of erection. 38 patients (93%) had a positive response to sildenafil and
      reached a penile rigidity sufficient to permit sexual intercourse. 3 patients
      dropped out because of non-response despite having increased the dosis up to 100
      mg. 22 patients (58%) showed functional erections 1 h after 50 mg sildenafil,
      whereas 14 (37%) required higher doses of 75-100 mg. By comparing the IIEF
      questionnaire scores before and after therapy, there was a significant
      improvement in erectile function and intercourse satisfaction from 9.2+/-4.4 SD)
      and 4.5 (+/-2.5 SD) to 25.5 (+/-4.2 SD) and 10.5 (+/-2.1 SD) points, respectively
      (p<0.05). Nearly 10% (4/41) suffered from side effects such as headache or
      dizziness. Two of them stopped therapy because of the side effects. At least 36
      patients (88%) continue treatment with sildenafil. Absence of both psychogenic
      (nonsomesthetic supraspinally elicited) and reflexive (somesthetic spinally
      elicited) erections, confirmed by urodynamical and electrophysiological findings
      (SSR perineum, BCR and pSSEP), seems to exclude a successful treatment. In
      contrast, SCI male patients with preserved function of at least one component of
      the erection phenomenon (psychogenic/reflexive) responded well to sildenafil and
      the dose required to achieve erections sufficient for sexual intercourse did not
      differ between the two groups. CONCLUSIONS: Sildenafil proves to be a valuable
      and safe therapeutic management in ED of SCI patients. Therefore, patient
      acceptance and satisfaction are high. The most common dose required to achieve a
      satisfying erection is 50 mg. The efficacy of sildenafil depends on sparing of
      either sacral (S2-S4) or thoracolumbar (T10-L2) spinal segments which, in this
      study, have been shown to be of relevance in mediating psychogenic erections in
      male SCI patients. Complete disturbance of any neurogenic impulses excludes
      successful treatment.

PMID- 10895012
TI  - Treatment of a benign prostatic hyperplasia by Nd:YAG laser - own experience.
AB  - OBJECTIVES: To evaluate the effectiveness and safety of visual laser ablation
      (VLAP) and interstitial laser coagulation (ILCP) versus transurethral resection
      of the prostate (TURP). PATIENTS AND METHODS: Altogether 259 consecutive patients
      with symptomatic benign prostatic hyperplasia (BPH) were treated by VLAP (n =
      117), ILCP (n = 30) or TURP (n = 112). VLAP was carried out using both contact
      and noncontact techniques, whereas ILCP using the technique described by
      Muschter. The results were obtained at a mean follow-up of 23 months (from 6 to
      48 months). IPSS, quality of life, maximum flow rate, and residual urine were
      evaluated preoperatively and at 3 and 6 months after operation in all patients.
      The results at 12, 24 and 48 postoperative months are available for 122, 86 and
      72 patients, respectively. RESULTS: Mean values of all outcome parameters
      improved during 6 postoperative months (p<0.05) in all groups of patients and
      subsequently remained unchanged during the 4-year postoperative period. There
      were no serious postoperative complications in the laser groups. Very good and
      good results were obtained in 71.3% patients after VLAP, in 89.3% patients after
      ILCP and 81.4% patients after TURP. CONCLUSION: Both VLAP and ILCP are safe
      methods with low risk of complications, however, they are less effective than
      TURP, which remains the gold standard for BPH patients requiring surgical
      treatment

PMID- 10895013
TI  - Age-stratified analysis of I-PSS and QoL values in spanish patients with symptoms
      potentially related to BPH.
AB  - OBJECTIVE: The main goal of the present study was to determine age-related
      symptom changes using a validated Spanish International Prostate Symptom Score (I
      PSS) and quality of life index (QoL) in Spanish patients with symptomatic benign
      prostatic hyperplasia (BPH). METHODS: A total of 2,875 patients with the clinical
      diagnosis of symptomatic BPH were evaluated. Data were collected during current
      medical practice in a national study. Patients were excluded if they had any
      previous prostate operation or suspicion of prostate cancer. I-PSS was self
      administered and compared with the physician's global impression. RESULTS: I-PSS
      symptoms, both voiding and storage symptoms, increased significantly with age
      (p<0.0001) as well as QoL (p<0.0017). A change in the I-PSS categories (minor,
      moderate and severe) was found with age, increasing severe symptomatic patients
      in the oldest groups. A significant correlation was found between I-PSS and QoL
      (r = 0.49, p<0.001), being this relationship linear and not significantly
      influenced by age. CONCLUSIONS: This study confirms reliable results using a
      validated Spanish I-PSS in a large national representative sample of Spanish
      patients with BPH symptoms. The age-stratified analysis showed that the natural
      progression of BPH with age was related to an increased symptomatology and
      bothersomeness, well reflected by increases in the I-PSS and QoL values.
      Nevertheless, the effect of symptomatology on quality of life was not strongly
      influenced by the age of the patient.

PMID- 10895015
TI  - Is one set of sextant biopsies enough to rule out prostate Cancer? Influence of
      transition and total prostate volumes on prostate cancer yield.
AB  - PURPOSE: Although the sextant biopsy technique has been widely used, concern has
      arisen that this method may not include an adequate sampling of the prostate,
      especially for large prostate volumes. We conducted a multicenter study in
      patients with PSA levels <10 ng/ml to determine the influence of the total and
      transition zone (TZ) volumes of the prostate for predicting whether one single
      set of biopsies was sufficient to rule out prostate cancer (PCa). These
      parameters were evaluated in patients in whom PCa was found after one set of
      systematic sextant biopsies and those in whom PCa was found after a repeat
      biopsy. MATERIALS AND METHODS: A total of 1,018 patients were included in this
      study. All underwent transrectal ultrasound-guided needle sextant and two TZ
      biopsies of the prostate. Total and TZ volumes of the prostate were measured
      (prolate ellipsoid method). From this cohort, all patients in whom a benign
      disease was found after the first set of biopsies underwent a second similar set
      of biopsies within 6 weeks. Only patients with PCa were included in this study,
      whether diagnosed on first or repeat biopsy. Uni- and multivariate statistical
      analysis using the SAS system (Cary, N.C., USA) and ROC curves were used to
      compare patients in whom the diagnosis was performed after the first set of
      biopsies and those who required a second set. RESULTS: Of the 1,018 patients, 344
      (33.8%) had PCa diagnosed, 285 (28%) after the first set of biopsies, and 59
      (8.1%) on repeat biopsy. As compared to patients diagnosed with PCa after the
      first set of biopsies, patients diagnosed after the second set had larger total
      prostate and TZ volumes (43.1+/-13.0 vs. 32.5+/-10.6 cm(3), p<0.0001 and 20.5+/
      8.3 vs. 12.8+/-6.0 cm(3), p<0.0001). ROC curves showed that total and TZ volumes
      of 45 and 22. 5 cm(3), respectively, provided the best combination of sensitivity
      and specificity for discriminating between patients diagnosed with PCa after the
      first from those diagnosed after a second set. CONCLUSION: In patients with total
      prostate volume >45 cm(3) and TZ >22.5 cm(3), a single set of sextant biopsies
      may not be sufficient to rule out PCa. In these patients, a repeat biopsy should
      be considered in case of a negative first biopsy.

PMID- 10895014
TI  - Naked DNA and adenoviral immunizations for immunotherapy of prostate cancer: a
      phase I/II clinical trial.
AB  - INTRODUCTION AND OBJECTIVES: Animal studies have indicated that the use of
      syngeneic dendritic cells that have been transfected ex vivo with DNA for tumor
      specific antigen results in tumor regression and decreased number of metastases.
      Additional studies have also suggested the possibility to modulate the dendritic
      cells in vivo either by 'naked' DNA immunization or by injecting replication
      deficient viral vectors that carry the tumor-specific DNA. Using the prostate-
      specific membrane antigen (PSMA) as a target molecule, we have initiated a
      clinical trial for immunotherapy of prostate cancer. The primary objective of the
      study was to determine the safety of the PSMA vaccine after repeated intradermal
      injections. METHODS: We have included the extracellular human PSMA DNA as well as
      the human CD86 DNA into separate expression vectors (PSMA and CD86 plasmids), and
      into a combined PSMA/CD86 plasmid. In addition, the expression cassette from the
      PSMA plasmid was inserted into a replication deficient adenoviral expression
      vector. Twenty-six patients with prostate cancer were entered into a phase I/II
      toxicity-dose escalation study, which was initiated in spring 1998. Immunizations
      were performed intradermally at weekly intervals. Doses of DNA between 100 and
      800 microg and of recombinant virus at 5x10(8) PFUs per application were used.
      RESULTS AND CONCLUSION: No immediate or long-term side effects following
      immunizations have been recorded. All patients who received initial inoculation
      with the viral vector followed by PSMA plasmid boosts showed signs of
      immunization as evidenced by the development of a delayed-type hypersensitivity
      reaction after the PSMA plasmid injection. In contrast, of the patients who
      received a PSMA plasmid and CD86 plasmid, only 50% showed signs of successful
      immunization. Of the patients who received PSMA plasmid and soluble GM-CSF, 67%
      were immunized. However, all patients who received the PSMA/CD86 plasmid and sGM
      CSF became immunized. The patients who did not immunize during the first round
      were later successfully immunized after a boost with the viral vector. The
      heterogeneity of the medical status and the presence in many patients of
      concomitant hormone therapy does not permit unequivocal interpretation of the
      data with respect to the effectiveness of the therapy. However, several
      responders, as evidenced by a change in the local disease, distant metastases,
      and PSA levels, can be identified. A phase II clinical study to evaluate the
      effectiveness of the therapy is currently underway.

PMID- 10895016
TI  - Use of percent free prostate-specific antigen as a predictor of the pathological
      features of clinically localized prostate cancer.
AB  - PURPOSE: To evaluate the usefulness of percent free serum prostate-specific
      antigen (PSA) as a predictor of the pathological features of prostate cancer.
      MATERIALS AND METHODS: Total and free serum PSA were measured preoperatively in
      220 consecutive patients with clinically localized prostate cancer who underwent
      radical prostatectomy. Organ-confined disease and favorable pathology were
      considered as the outcomes for this study. RESULTS: Percent free serum PSA was
      not able to predict these outcomes in the overall population. However, it could
      significantly predict favorable pathology in a subset of patients in whom digital
      rectal examination (DRE) was normal and total PSA ranged from 4.1 to 10 ng/ml. A
      11% cutoff provided a significant distribution with an odds ratio of 2.8 (95%
      confidence interval 1.1-7.0), a positive predictive value of 63. 3% and a
      negative predictive value of 46.3%. CONCLUSIONS: According to these results, we
      suggest that percent free PSA may provide additional information for the staging
      of clinically localized prostate cancer. However, the reference population for
      its usefulness would be those patients with normal DRE and total PSA between 4.1
      and 10 ng/ml.

PMID- 10895017
TI  - p21(WAF-1/CIP-1), a downstream regulator of functional p53 loss, in transitional
      cell carcinoma of urothelium.
AB  - OBJECTIVES: The expression of p21(WAF-1/CIP-1), a downstream regulator of p53, is
      a universal cycline-dependent kinase inhibitor. The aim of this study is to
      determine whether p21 expression could be used as a prognostic marker in
      urothelial carcinomas. METHODS: By use of immunohistochemistry, we examined the
      expression of p21(WAF-1/CIP-1) in 60 patients with urothelial carcinomas and
      compared the results with the status of nuclear p53 and mdm2 accumulation,
      expression of type IV collagen in the basement membranes and upregulation of
      metalloproteinases (MMP-1, MMP-2, MMP-9). RESULTS: p21(WAF-1/CIP-1)
      immunoreactivity was observed in 51.7% of the tumors, and in only 39% of the
      tumors with functional p53 loss (nuclear accumulation of p53 and/or mdm2).
      p21(WAF-1/CIP-1) overexpression was not associated with grade and stage of the
      tumors and presence or absence of concomitant CIS. Moreover, p21(WAF-1/CIP-1)
      overexpression was not associated with upregulation of metalloproteinases or
      destruction of type IV collagen of basement membranes. CONCLUSIONS: Our results
      suggest that p21(WAF-1/CIP-1) expression is regulated by both p53-dependent and
      independent pathways and is not related to grade, stage or potential markers of
      invasion in urothelial carcinomas.

PMID- 10895018
TI  - Heat-induced cellular damage and tolerance in combination with adriamycin for the
      PC-3 prostate cancer cell line: relationships with cytotoxicity, reactive oxygen
      species and heat shock protein 70 expression.
AB  - OBJECTIVE: To analyze the relationships among the antitumor effect of
      chemothermotherapy, generation of reactive oxygen species (ROS), and expression
      of heat shock protein 70 (HSP-70) in the PC-3 prostate cancer cell line.
      MATERIALS AND METHODS: Changes in cell proliferation, cell cycle fractions,
      intracellular ROS accumulation and HSP-70 expression were examined after
      thermotherapy of PC-3 cells at 41, 42, 43 and 44 degrees C and/or simultaneous
      treatment with Adriamycin for 1 h, using the trypan blue dye exclusion method,
      flow cytometry, fluorescent 2', 7'-dichlorofluorescein (DCF) assay, and Western
      blot analysis. RESULTS: A significant decrease in the number of viable cells was
      observed with chemothermotherapy compared with thermotherapy at 42, 43, or 44
      degrees C (p<0.05). DNA distribution histograms revealed cell accumulation in the
      S-G(2)/M phase after thermotherapy at 43 degrees C and after chemothermotherapy
      at 37, 41, 42 and 43 degrees C. After thermotherapy and chemothermotherapy at 44
      degrees C, DNA histograms revealed no accumulation of cells with S-G(2)/M DNA
      content and cells exhibited a marked loss of viability. A significant increase in
      DCF production was observed with chemothermotherapy compared with thermotherapy
      at 42, 43 or 44 degrees C (p<0.05, p<0.01 and p<0.01, respectively). HSP-70
      levels increased linearly with increasing temperature. HSP-70 levels after
      thermotherapy and chemothermotherapy increased with time and reached plateaus at
      30 min, whereas the level after thermotherapy at 44 degrees C decreased at 60
      min. CONCLUSIONS: In conclusion, one possible synergism in cytotoxic effects of
      chemothermotherapy and Adriamycin could be evaluated by the relationship between
      ROS accumulation and HSP-70 expression in the PC-3 prostate cancer cell line.

PMID- 10895019
TI  - Production of interleukins 1beta, 6 and 8 and tumor necrosis factor alpha in
      separated and cultured endometrial and endometriotic stromal and epithelial
      cells.
AB  - The production of IL-1beta, IL-6, IL-8 and TNF-alpha was studied in short-time
      culture of separated stromal and epithelial cells. The cytokine secretion into
      culture medium was analyzed using immunoassay to evaluate the cytokine protein
      levels and bioassay to assess the bioactivity of the cytokines. Tissue samples of
      endometrium and ovarian endometriomas were obtained from 4 patients operated on
      for clinical reasons. Only IL-8 was found in all samples. IL-1beta and TNF-alpha
      were detected in the culture medium from most stromal cell samples, but in fewer
      media from epithelial cell samples. IL-6 was measurable in a few medium samples.
      Few of the samples displayed a bioactivity. There was no obvious difference
      between endometrium and endometriotic cell samples besides the production of IL-8
      that seems to be lower in endometriotic tissue.

PMID- 10895020
TI  - Serum angiogenin levels during menstrual cycle and pregnancy.
AB  - OBJECTIVE: To evaluate alterations in maternal circulating angiogenin levels with
      advancing gestation and to assess the effect of labor stress on serum angiogenin
      levels in neonates delivered vaginally and by cesarean section. METHODS: The
      maternal circulating angiogenin concentrations were compared in 37 normotensive
      nonpregnant women, in 60 normotensive pregnant women from 7 to 41 weeks of
      gestation, and in 12 normotensive postpartum women on the 3rd puerperal day. The
      serum angiogenin concentrations were also measured in 12 patients with threatened
      premature labor. Moreover, maternal and fetal serum angiogenin samples before and
      after delivery were used to determine differences in 12 neonates delivered
      vaginally and in 11 neonates delivered by elective cesarean section. The serum
      angiogenin level was measured using an enzyme-linked immunosorbent assay.
      RESULTS: There was no significant difference in serum angiogenin levels during
      each phase of the menstrual cycle. The serum angiogenin levels were decreasing
      until 15 weeks of gestation and increasing thereafter. There was no significant
      difference in serum angiogenin levels between normal pregnant women and in
      patients with threatened premature labor. Labor stress did not affect either
      maternal or fetal serum angiogenin concentrations. The serum angiogenin levels of
      the neonates were significantly lower than those in maternal serum after both
      vaginal delivery and delivery by cesarean section. CONCLUSION: These results
      suggest that regulatory mechanisms of angiogenin may exist during pregnancy.

PMID- 10895021
TI  - Menstruum induces changes in mesothelial cell morphology.
AB  - In previous studies, we have shown that menstrual endometrium preferentially
      adheres to the subepithelial lining of the peritoneum. It remains to be
      elucidated, however, whether this damage is preexisting or inflicted by the
      menstrual tissue itself. We hypothesized that the menstrual tissue itself damages
      the peritoneum. To investigate this, the viability of menstrual endometrial
      tissue in peritoneal fluid (PF) was evaluated and the morphologic changes in the
      mesothelial cells were studied by in vitro cocultures of menstruum with
      mesothelial cell monolayers. Menstruum was collected with a menstrual cup.
      Endometrial tissue was isolated from the menstruum, resuspended in culture medium
      or in the cell-free fraction of PF and cultured for 24, 48 or 72 h. A 3(4, 5
      dimethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed
      to obtain a relative measure of viable adhered endometrial cells. Mesothelial
      cells isolated from human omental tissue were cultured on Matrigel or uncoated
      plastic. At confluence, overnight cocultures were performed and scanning electron
      microscopy was used to evaluate the morphologic changes. The viability of
      endometrial fragments was 84% (n = 36, p < 0.05), 82% (n = 27, not significant)
      and 104% (n = 14, not significant) when cultured in the cell-free fraction of PF
      for 24, 48 and 72 h, respectively, when compared to medium with 10% fetal calf
      serum. Menstrual endometrial fragments or menstrual serum added to and cocultured
      with mesothelial cells induced severe morphologic alterations of the latter,
      including retraction, shrinking and gap formation. Similar morphologic changes
      were observed when mesothelial cells were cocultured with menstrual endometrial
      fragments in PF or in culture inserts. Incubation with conditioned medium from
      cultured menstrual endometrium induced similar but less pronounced changes in
      morphology. In conclusion, menstrual endometrial fragments remain viable in PF in
      vitro for at least 72 h. Antegradely shed menstruum induces changes in
      mesothelial cell morphology, including retraction and shrinking with exposure of
      the underlying surface. These findings suggest that menstruum is harmful to the
      peritoneal lining. Therefore, by local destruction of the mesothelial layer,
      menstrual endometrium is able to create sites for adhesion.

PMID- 10895022
TI  - Transforming growth factor-beta(1), -beta(2), -beta(3) and their type I and II
      receptors in human term placenta.
AB  - Expression of transforming growth factor (TGF)-beta(3) as well as cellular
      localization of TGF-beta receptors has not been demonstrated in placenta. TGF
      beta receptor type I (RI) and type II (RII) are required to transmit TGF-beta
      signals, therefore the determination of cells expressing both receptors in
      concert is necessary to identify target cells for TGF-beta. We investigated
      presence and localization of TGF-betas and their receptors (RI, RII) in human
      term placenta using reverse transcription-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. RT-PCR showed that messenger RNA for TGF-beta(1), -beta(2),
      -beta(3), and RI and RII is present in human term placenta. We found intense
      staining for all TGF-beta isoform and receptor proteins in the
      syncytiotrophoblastic layer, chorionic plate, and in cells of the extravillous
      trophoblasts using immunohistochemistry. The simultaneous expression of ligands
      and their receptors support the hypothesis that TGF-beta may play an important
      role in regulating growth, differentiation, and function of the human placenta.

PMID- 10895023
TI  - Fetal binocular distance: no differences between ethnic groups.
AB  - OBJECTIVE: The aim of this study was to detect if interethnic differences for
      fetal binocular distance exist between the autochthonous Belgian population and
      immigrants from Turkey or Morocco, and to evaluate the need for different
      reference charts by ethnicity. METHODS: A prospective cross-sectional study was
      performed. In 246 pregnant women who presented for routine prenatal ultrasound
      between 18 and 40 weeks of gestation age the binocular distance was measured.
      Polynomial regression was performed for the three ethnic groups. RESULTS: The
      population consisted of 171 autochthonous Belgian women, 31 women from Turkish
      origin and 44 women from Moroccan origin. A statistically significant difference
      for the fetal binocular distance was noted between the Moroccan versus the
      autochthonous Belgian and Turkish fetuses (F test, p = 0. 047). The order of
      magnitude of this statistical difference is extremely small and does not result
      in clinical relevance. CONCLUSION: A small, but statistically significant
      difference exists for the fetal binocular distance between fetuses of Moroccan
      origin versus those of autochthonous Belgian or Turkish origin. This difference
      is of no clinical importance and there is no need to adapt reference charts for
      ethnicity when studying these three groups.

PMID- 10895024
TI  - Excessive use of cesarean section for the second twin?
AB  - BACKGROUND: In Sweden, the frequency of cesarean section of the second twin after
      vaginal birth of the first twin has increased in recent years. METHODS: To
      investigate the indications for second twin cesarean sections, all twin
      deliveries at Huddinge University Hospital from 1995 to 1997 were reviewed
      retrospectively. The rates of cesarean section for the second twin were compared
      with figures from the whole country, based on the Swedish medical birth register.
      RESULTS: Thirty-one percent of all twin deliveries had a spontaneous onset and
      spontaneous vaginal delivery. The total twin cesarean section rate, including
      cesarean section for the second twin, was 45% at Huddinge University Hospital in
      1995-1997 and 44% in Sweden in 1995. Cesarean section for the second twin after
      vaginal delivery of the first twin occurred in 11%. On review, 2/3 of the
      cesarean sections for the second twin were considered potentially avoidable.
      CONCLUSION: In normal twin pregnancies with vertex/nonvertex presentation, the
      favorable fetal outcome and also the maternal risks associated with cesarean
      section support vaginal delivery as the recommended delivery route. Extraction or
      version of a second nonvertex twin should be attempted before cesarean section
      for this twin is performed.

PMID- 10895025
TI  - Urinary orotic acid levels in normal pregnancy and pregnancy-induced
      hypertension.
AB  - Our objective was to study the urinary levels of orotic acid in normal pregnancy
      and in pregnancy-induced hypertension. Such levels were measured using high
      performance liquid chromatography with column-switching. The levels of urinary
      orotic acid (micromol/g creatinine) in normal pregnancy (n = 14) were 6.9 +/- 2.3
      (first trimester), 10.1 +/- 2.4 (20 weeks) and 12.0 +/- 3.7 (30 weeks). In
      pregnancy-induced hypertension (n = 14), the corresponding levels were 6.5 +/-
      1.7, 7.8 +/- 2.7 and 7.6 +/- 2.3, respectively. Normal pregnant subjects
      individually showed a significant elevation at 20 and 30 weeks of gestation as
      compared with those in the first trimester (p < 0.01). A high consumption of
      arginine in nitric oxide production during normal pregnancy may cause a
      physiological elevation of urinary orotic acid. The absence of an elevation in
      pregnancy-induced hypertension may be associated with a decrease in nitric oxide
      production.

PMID- 10895026
TI  - Altered thiol status in preeclampsia.
AB  - Thirty preeclamptic, 30 normotensive pregnant and 25 healthy nonpregnant women
      were analyzed with regard to the antioxidant system (thiols and superoxide
      dismutase, SOD). In preeclampsia both plasma and lysate thiol levels were
      significantly lower compared to controls (p < 0.001). SOD levels were higher in
      normotensive pregnant women, but were lower in preeclamptic compared to
      nonpregnant women. This finding of antioxidant changes in the red blood cell
      suggests that red cell dysfunction is fundamental in the development of
      preeclampsia, and similar alterations in the balance of the thiol could be
      present across the endothelial cell membrane.

PMID- 10895027
TI  - Sublingual isosorbide dinitrate in the acute control of hypertension in patients
      with severe preeclampsia.
AB  - The objective of this study was to evaluate the effectiveness of sublingual
      isosorbide dinitrate (ID) in the acute control of hypertension in patients with
      severe preeclampsia. A randomized, double-blind clinical trial with a
      preinclusion period of response to hydration and rest was performed in 60
      patients with severe preeclampsia. The treatment group (30 patients) received 5
      mg of sublingual ID, a dose that could be repeated on a second occasion. The
      control group consisted of 30 patients who received placebo. Both groups
      continued with rest and hydration during the study. Maternal blood pressure and
      fetal heart rate were measured in all patients every 10 min until 1 h was
      completed. Treatment was considered effective when the diastolic blood pressure
      could be reduced to between 80 and 100 mm Hg. ID was effective in 56.6% of the
      patients in the first 10 min after its administration and in 96. 6% from 40 to 60
      min. In the treatment group the systolic and diastolic blood pressures dropped
      gradually from 171 +/- 13 and 113 +/- 8 mm Hg, respectively, to 136 +/- 14 and 87
      +/- 9 mm Hg. In the placebo group, blood pressure was not reduced. There was no
      significant difference in fetal heart rate between both groups throughout the
      study. In conclusion, ID was shown to be effective in the acute control of
      hypertension in patients with severe preeclampsia, where high blood pressure
      persists after a period of rest and hydration.

PMID- 10895028
TI  - Endometrial response to sexual steroids as assessed by prostaglandin F(2alpha)
      output in explant culture and hormone receptor expression.
AB  - The objective of this study was to evaluate the endometrial response to sexual
      steroids in organ culture using two means: prostaglandin (PG) F(2alpha) output in
      medium culture and steroid receptor immunoexpression in tissue. Human endometrium
      samples were classified in homogeneous and heterogeneous proliferative or
      secretory subsets. In proliferative endometrium explant culture, progesterone
      (10(-7) M) induced a significant decrease in PGF(2alpha) output, but this was not
      the case in secretory endometrium, whereas no significant effect of estradiol
      (10(-8) M) was observed. Before culture, homogeneous and heterogeneous
      proliferative endometrium presented the same pattern of estradiol receptor (ER)
      and progesterone receptor (PR) expression evaluated by quantitative
      immunocytochemistry. After culture, immunoreactive ER and PR were detected on the
      explant. PR immunoexpression rates after culture were lower than before culture
      in glands on homogeneous proliferative and in stroma on heterogeneous
      proliferative endometrium explants without in vitro steroid addition. In
      secretory endometrium, no significant difference was observed between ER or PR
      immunoexpression rates before culture and after culture. These results provided
      the hormonal receptivity status of endometrium after culture and will thus serve
      as a reference for evaluating in vitro steroid effects on endometrium explants.
      Our preliminary results suggest that cultures of endometrium explants are a valid
      model for studying the effects of hormonal treatment on homogeneous as well as
      heterogeneous endometrium. These data could be particularly relevant for
      evaluating the potential response to hormone stimulation and treatment of
      endometria sampled in perimenopausal patients.

PMID- 10895029
TI  - Laparoscopically assisted vaginal hysterectomy using the light-endorsed
      transvaginal section technique versus the conventional method: a preliminary
      study.
AB  - Laparoscopically assisted vaginal hysterectomy (LAVH) is now being used by an
      increasing number of gynecologists. However, problems, such as the long operating
      time, the inherent difficulty of the technique, and limitations of the skills of
      the surgeons, still exist. Pelvic adhesion, especially in the vesicouterine
      reflection, may increase the difficulty and morbidity of the operation. We here
      describe a simple technique, called light-endorsed transvaginal section (LETS),
      which can facilitate the effectiveness and safety of LAVH. We have designed
      prospective studies to compare results obtained in 50 cases treated using LAVH
      plus LETS (study group) with those obtained in 50 cases treated by conventional
      LAVH (control group). We further divided the study group into 25 'complicated'
      cases (with pelvic adhesion) and 25 'easy' cases (without pelvic adhesion). The
      results show that the LETS technique is a simple, safe, and easy way of
      increasing the efficacy of LAVH, especially as a supplement to LAVH in the
      presence of pelvic adhesions.

PMID- 10895030
TI  - Comparison of vaginal shapes in Afro-American, caucasian and hispanic women as
      seen with vinyl polysiloxane casting.
AB  - Full vinyl polysiloxane casts of the vagina were obtained from 23 Afro-American,
      39 Caucasian and 15 Hispanic women in lying, sitting and standing positions. A
      new shape, the pumpkin seed, was found in 40% of Afro-American women, but not in
      Caucasians or Hispanics. Analyses of cast and introital measurements revealed:
      (1) posterior cast length is significantly longer, anterior cast length is
      significantly shorter and cast width is significantly larger in Hispanics than in
      the other two groups and (2) the Caucasian introitus is significantly greater
      than that of the Afro-American subject.

PMID- 10895031
TI  - p53 polymorphism and human papillomavirus infection in Hong Kong women with
      cervical cancer.
AB  - In this study we investigated the involvement of p53 polymorphism at codon 72,
      the infection and typing of human papillomavirus (HPV) and the correlation of p53
      polymorphism with HPV type and other clinicopathologic characteristics in 72 Hong
      Kong women with cervical cancer. We developed a simple and nonradioactive method
      for determining polymorphism at codon 72 of the p53 gene. The homozygous p53
      arginine allele (Arg/Arg) was detected in 22 (31%), the homozygous p53 proline
      allele (Pro/Pro) in 14 (19%) and the heterozygous allele (Arg/Pro) in 36 (50%)
      cases, respectively. Using the consensus primers MY11 and MY09, HPV infection was
      detected in 55 of 72 (76%) cases. The prevalent types were HPV-16 (55%), HPV-18
      (16%) and HPV-58 (9%). The number of HPV-positive cases with Arg/Arg, Pro/Pro and
      Arg/Pro were 17 (31%), 12 (22%) and 26 (47%), respectively. The p53 polymorphism
      at codon 72 was not significantly correlated with any of the HPV types (p >
      0.05). No striking overrepresentation of homozygous arginine-72 p53 was observed
      in HPV-associated cervical cancer. The results in this study did not show that
      any p53 polymorphic form has a prognostic significance for cervical cancer.

PMID- 10895032
TI  - Primary vaginal stone in an 11-year-old recumbent girl.
AB  - Primary vaginal stones are extremely rare, particularly in young women. We
      describe the occurrence of a primary vaginal calculus in a severely retarded 11
      year-old girl who was not diagnosed until she was examined using computerized
      tomography. We postulate that the calculus was formed as a consequence of urinary
      contamination of the vagina in association with incontinence and prolonged
      maintenance in a recumbent posture.

PMID- 10895033
TI  - Hematometra in postmenarchal adolescent girls: a report of two cases.
AB  - We report two cases of unicornuate uterus with functioning rudimentary horn to
      highlight that Mullerian duct anomalies should be considered in the differential
      diagnosis of severe dysmenorrhoea even in normally menstruating girls.

PMID- 10895034
TI  - Osteochondroma of the pubic symphysis associated with sexual disturbance.
AB  - Osteochondroma of the pubic symphysis is a rare benign skeletal tumor. We report
      here a case of an osteochondroma of the pubic symphysis associated with a sexual
      disturbance, where a computed tomography scan clearly showed a tumor lesion of
      the pubic symphysis. The case is reported not only because of its rarity but also
      because it is important that gynecologists should bear this disease in mind,
      since a patient with this tumor may not visit an orthopedist but a gynecologist.

PMID- 10895035
TI  - Loss of imprinted genes and paternal SUR1 mutations lead to focal form of
      congenital hyperinsulinism.
AB  - Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a heterogeneous
      disorder characterized by profound hypoglycaemia due to inappropriate
      hypersecretion of insulin. An important diagnostic goal is to distinguish
      patients with a focal hyperplasia of islet cells of the pancreas (FoPHHI) from
      those with a diffuse abnormality of islets (DiPHHI), because the management
      differs significantly. The intriguing similarity between islet cell hyperplasia
      and tumourigenesis prompted us to investigate whether the imprinted genes in the
      11p15 region are involved. Results showed that diffuse forms are caused by
      constitutional homozygous or compound heterozygous mutations of the SUR1 gene. In
      contrast, focal forms are caused by loss of the maternally inherited 11p15
      region, resulting in both loss of the maternally expressed tumour suppressor
      genes accounting for hyperplasia and somatic reduction to hemizygosity or
      homozygosity of the paternally inherited SUR1, limited to the lesion. Thus, this
      somatic disorder, which leads both to beta-cell proliferation and to
      hyperinsulinism, can be considered the somatic equivalent, restricted to a
      microscopic focal lesion, of constitutional uniparental disomy associated with
      unmasking of a heterozygous parental mutation.

PMID- 10895036
TI  - Neonatal diabetes: new insights into aetiology and implications.
AB  - Neonatal diabetes mellitus (NDM) is defined as hyperglycaemia occurring in the
      first few weeks of life. It can be either transient (TNDM) or permanent (PNDM),
      and until recently, little was known about the condition. A cohort of 30 infants
      with a history of TNDM has been studied, and findings have suggested that NDM
      does not have the same aetiology as classical type 1 childhood diabetes.
      Uniparental isodisomy of chromosome 6 and an unbalanced duplication of paternal
      chromosome 6 have both been described as a genetic basis for TNDM in over 75% of
      the cases. In addition, cerebellar hypoplasia and Walcott-Rallison syndrome have
      been associated with PNDM, suggesting an autosomal recessive inheritance pattern;
      furthermore, a mutation in the gene insulin promoter factor 1 has been identified
      as a cause of pancreatic agenesis in PNDM. In the long term, TNDM may reduce beta
      cell functional capacity and present a predisposition to type 2 diabetes
      mellitus.

PMID- 10895037
TI  - Molecular pathogenesis of neonatal hypothyroidism.
AB  - In patients with congenital hypothyroidism (CH), the autosomal recessive
      inheritance of mutations of thyroid peroxidase, thyroglobulin and the NIS and
      pendrin genes encoding for sodium iodide transporters has been identified. CH due
      to thyroid dysgenesis was considered to be a sporadic disease, but recently,
      inheritable defects of thyroid development have been described. The autosomal
      recessive inheritance of mutations of the thyroid-stimulating hormone receptor
      gene was recognized in patients with CH and thyroid hypoplasia, while autosomal
      dominant mutations of the Pax-8 gene were described in patients with thyroid
      dysgenesis. In addition, analysis of mutations of the beta-thyrotropin gene has
      resulted in a new understanding of the pathogenesis of central CH. Molecular
      genetic studies in patients with CH detected by newborn screening will provide
      the information necessary for genetic counselling and may help to explain the
      less favourable outcome present in 5-10% of the patients.

PMID- 10895038
TI  - Children with septo-optic dysplasia - how to improve and sharpen the diagnosis.
AB  - The data in this article are based on investigations performed in 25 children
      with suspected septo-optic dysplasia (SOD). There are many signs and methods that
      help in the diagnosis of SOD. In particular, the ocular fundus, abnormalities of
      the hypothalamo-pituitary axis and other midline brain structures should be
      described. In order to achieve a more holistic and functional diagnosis, the
      degree of neurological, neuropsychiatric and psychological involvement should
      also be stated. It has been suggested that SOD is associated with autosomal
      recessive inheritance, and it can be speculated that it is the result of genetic
      and environmental influences early in gestation. An early diagnosis can
      favourably influence the outcome of the affected child.

PMID- 10895039
TI  - Molecular genetics of septo-optic dysplasia.
AB  - Septo-optic dysplasia (SOD) is a highly variable condition characterized by
      midline neurological abnormalities associated with pituitary hypoplasia and optic
      nerve hypoplasia. The aetiology is unknown. Mutant mice, in which a novel
      homeobox gene, Hesx1, has been disrupted, exhibit a phenotype that resembles the
      phenotype of SOD. We therefore wished to explore the possibility that this gene
      is implicated in SOD. We cloned and sequenced the human homologue HESX1 and
      screened for mutations in affected individuals using single-stranded
      conformational polymorphism analysis, followed by cloning and sequencing of any
      exons which showed a band shift. Two siblings with SOD were homozygous for an
      Arg53Cys missense mutation within the HESX1 homeodomain, leading to a loss of in
      vitro DNA binding. Subsequently, we have identified heterozygous mutations in
      HESX1 that are associated with milder pituitary phenotypes. Our studies indicate
      a vital role for Hesx1/HESX1 in forebrain and pituitary development in mouse and
      man, and hence in some cases of SOD.

PMID- 10895040
TI  - How can molecular biology contribute to the management of congenital adrenal
      hyperplasia?
AB  - The most common form of congenital adrenal hyperplasia is due to a deficiency of
      21-hydroxylase (21OHD) activity and is caused by a mutation in the CYP21 gene. By
      genotyping patients, new and important information can be gained, including
      presence or absence of 21OHD in borderline cases, determining the severity of
      disease and identifying heterozygote carriers. Current management of patients
      with 21OHD involves administering sufficient glucocorticoids to suppress excess
      adrenal androgen secretion, but not so much that bone growth and mineralization
      are impaired. New management strategies have been proposed and include
      administering only substitution doses of corticosteroids and counteracting side
      effects by administering an anti-androgen and aromatase inhibitor. Adrenalectomy
      has also been proposed. Further investigation into these approaches is necessary.

PMID- 10895041
TI  - Neonatal endocrinology of abnormal male sexual differentiation: molecular
      aspects.
AB  - Normal male sexual differentiation is a complex mechanism, depending on genetic
      and hormonal control. The bipotent gonad arises at the genital ridge under the
      control of autosomal genes which are also involved in the formation of other
      organs. Progression towards testicular differentiation is mediated through both
      autosomal and gonosomal genes, leading to alignment of Sertoli cells and Leydig
      cells. Within the latter, androgen formation is induced by human chorionic
      gonadotrophin and luteinizing hormone. The influence of testosterone and
      dihydrotestosterone leads to differentiation of epidydimis, vasa deferentia,
      prostate and external genitalia. Androgens mediate their action through the
      androgen receptor, a nuclear transcription factor controlling the regulation of
      so far unknown target genes. Genetic variations within this pathway interrupt
      normal male development and will lead to malformation of external and/or internal
      genitalia.

PMID- 10895042
TI  - Neonatal and post-natal growth.
AB  - Growth velocity is higher in late intra-uterine and early post-natal life than at
      any time thereafter, and accurate measurements are essential for appropriate
      monitoring. The accuracy with which such measurements are made and recorded is
      frequently questionable, however, and short- and medium-term changes in growth
      may be difficult to interpret in the light of normal variations in the pattern of
      growth. Infants who are small at birth must be accurately classified because
      intra-uterine growth retardation and small for gestational age have different
      implications for both causation and outcome. Prediction of expected growth on the
      basis of mid-parental height is essential but frequently omitted. Post-natal
      growth impairment is common in pre-term infants and is often rapid in onset. Poor
      growth may continue for many months, and catch-up may be incomplete. Early growth
      failure may have a significant influence on subsequent morbidity and mortality.

PMID- 10895043
TI  - Growth hormone and growth factors during perinatal life.
AB  - Pituitary growth hormone (GH) is present in early pregnancy in the fetal
      circulation. The concentrations are higher than ever found during life, due to an
      unrestrained, basal secretion. GH receptors develop around midpregnancy, when
      they are present in low concentrations, and there is a rapid increase during the
      first months of life. The function of fetal GH - characterized by a nearly
      complete GH resistance - is largely unclear: there is only a small effect on
      longitudinal growth, and the regulation of growth factors is independent of GH.
      Possibly, metabolic effects of GH on fat and glucose metabolism and body
      composition are of greater importance. During the first months of life, the rapid
      fetal (GH-independent, nutrition-dependent) growth decelerates, a process that is
      partly compensated by the onset of GH-dependent longitudinal growth.

PMID- 10895044
TI  - Long-term results with growth hormone therapy in idiopathic hypopituitarism.
AB  - More than 30 years after its introduction, growth hormone (GH) treatment is well
      established in children with GH deficiency. Nevertheless, the long-term results
      of this therapy, expressed as height, are generally considered unsatisfactory. We
      report on results obtained in a group of GH-deficient children who were treated
      with daily injections of recombinant GH within the first 5 years of life and who
      reached an adult height very close to their target height. The full catch-up
      growth to the target height demonstrated in these patients suggests that
      replacement therapy should be started early and continued until adulthood. Height
      at onset of puberty is an important variable which might significantly influence
      the adult height. The significant and prolonged influence of birth weight on
      growth response to GH therapy underlines the important role of fetal growth in
      planning early treatment of GH-deficient children.

PMID- 10895045
TI  - Metabolic consequences of growth hormone treatment in paediatric practice.
AB  - No metabolic side-effects of clinical significance have been reported during a 5
      year study of growth hormone (GH) therapy in children with GH deficiency, Turner
      syndrome, idiopathic short stature or chronic renal insufficiency. In particular,
      insulin levels increase but remain within the normal range, as do glucose and
      haemoglobin A(1c). A recent study showed that the effects of growth on insulin
      sensitivity in prepubertal children with idiopathic short stature represent the
      changes in carbohydrate tolerance observed during normal adolescence. Thus, GH
      treatment may lead to prolongation of the physiological state of insulin
      resistance observed in normal puberty. Insulin levels during the fasting state
      and 2 h after a standard glucose load showed no further rise after the first 3
      years of continuous GH therapy. The hyperinsulinaemia observed during GH therapy
      may, therefore, amplify the anabolic effects of insulin on protein metabolism
      during puberty.

PMID- 10895046
TI  - Growth hormone and neurofibromatosis.
AB  - Data collected from 102 neurofibromatosis (NF) children with growth hormone (GH)
      deficiency (GHD) who were receiving GH replacement therapy were reviewed to
      assess the efficacy and safety of GH therapy in this condition. GH was
      administered at a mean dose of 0. 18 mg/kg/week. During the 1st year the median
      height velocity increased significantly from 4.2 cm/year before treatment to 7.1
      cm/year, and the median height standard deviation score increased from -2.4 to 
      1.9. The response to therapy, however, was not as good as that observed in
      patients with idiopathic GHD. GH therapy did not influence the progression of any
      of the features of NF, including intracranial tumours, and was not associated
      with an excess of other adverse events. We conclude that GH treatment of NF
      patients with GHD is beneficial in terms of improved growth rate and is well
      tolerated.

PMID- 10895047
TI  - Growth hormone therapy in noonan syndrome.
AB  - Noonan syndrome (NS) is an autosomal dominant disorder that can be difficult to
      diagnose. Growth retardation is a consistent feature, however, and although
      children are not typically growth hormone (GH) deficient, a minority may have
      suboptimal GH levels. An ongoing multicentre study examining the safety and
      efficacy of GH therapy in NS showed increases in height standard deviation scores
      (SDS; p < 0. 0001) and height velocity (p < 0.0001) after 12 months of GH at
      pharmacological doses. There was no increase in mean maximal cardiac left
      ventricular wall thickness during the 12-month treatment period. Long-term follow
      up data covering 3 years of GH therapy showed sustained increases in height SDS
      and height velocity compared with baseline (p < 0.02). Further large and
      appropriately controlled studies of high-quality design are essential to further
      our understanding of NS and to establish the long-term safety and efficacy of GH.

PMID- 10895048
TI  - Treatment of juvenile rheumatoid arthritis with growth hormone.
AB  - Severe growth retardation and profoundly altered body composition are observed in
      children with juvenile chronic arthritis receiving glucocorticoids. This study
      assessed the effects of growth hormone (GH) on height velocity, body composition
      and bone density. Fourteen patients were treated with GH (1.4 U/kg/week) for 1
      year and then studied for a 2nd year off GH. The treatment increased insulin-like
      growth factor 1 and insulin-like growth factor binding protein 3 plasma levels.
      All patients showed an increase in height velocity. Lean body mass increased by
      12%. After the cessation of GH therapy, height velocity fell to pretreatment
      values, and weight and fat mass increased markedly. Bone formation and resorption
      markers significantly increased during treatment and returned to pretreatment
      values after discontinuation of GH treatment. These results suggest that GH may
      partially counteract the adverse effects of glucocorticoids on growth and
      metabolism in patients with chronic inflammatory disease.

PMID- 10895049
TI  - Growth hormone and adipocyte function in obesity.
AB  - In obesity, growth hormone (GH) secretion is impaired which is considered a
      consequence rather than a cause of obesity. GH regulates the expression of GH
      receptor and the synthesis of insulin-like growth factor I (IGF-I) in adipocytes.
      Although GH hyposecretion in obesity may decrease the generation of IGF-I in each
      adipocyte, increased amounts of IGF-I and GH-binding protein could be secreted
      from the excessively enlarged amounts of adipose tissue. This may contribute to
      the normal/high serum-IGF-I and high GH-binding protein levels in obesity.
      Hyperinsulinemia and increased GH receptor activity may also affect the GH-IGF-I
      axis. Favorable effects of GH treatment have been observed in obese children and
      adults. GH treatment decreases adiposity, reduces triglyceride accumulation by
      inhibiting lipoprotein lipase and enhances lipolysis both via increased hormone
      sensitive lipase activity and via induction of beta adrenoreceptors. GH treatment
      also has a favorable effect on obesity-associated dyslipidemia, but the effects
      on insulin sensitivity have been conflicting.

PMID- 10895050
TI  - Adeno-associated virus-based vectors in gene therapy.
AB  - Adeno-associated virus (AAV) vectors were shown capable of high efficiency
      transduction of both dividing and nondividing cells and tissues. AAV-mediated
      transduction leads to stable, long-term transgene expression in the absence of
      apparent immune response. These properties and the broad host range of AAV
      vectors indicate that they constitute a powerful tool for gene therapy purposes.
      An additional potential benefit of AAV vectors is their ability to integrate site
      specifically in the presence of Rep proteins which can be expressed transiently,
      thus limiting their suspected adverse effects. The major restrictions of AAV as
      vectors are their limited genetic capacity and strict packaging size constraint
      of less than 5 kb. Another difficulty is the labor-intensive and expensive
      procedure for the production and packaging of recombinant AAV vectors. The major
      benefits and drawbacks of AAV vectors and advances made in the past 3 years are
      discussed.

PMID- 10895051
TI  - Inhibition of ras oncogene: a novel approach to antineoplastic therapy.
AB  - The most frequently detected oncogene alterations, both in animal and human
      cancers, are the mutations in the ras oncogene family. These oncogenes are
      mutated or overexpressed in many human tumors, with a high incidence in tumors of
      the pancreas, thyroid, colon, lung and certain types of leukemia. Ras is a small
      guanine nucleotide binding protein that transduces biological information from
      the cell surface to cytoplasmic components within cells. The signal is transduced
      to the cell nucleus through second messengers, and it ultimately induces cell
      division. Oncogenic forms of p21(ras) lead to unregulated, sustained signaling
      through downstream effectors. The ras family of oncogenes is involved in the
      development of both primary tumors and metastases making it a good therapeutic
      target. Several therapeutic approaches to cancer have been developed pointing to
      reducing the altered gene product or to eliminating its biological function: (1)
      gene therapy with ribozymes, which are able to break down specific RNA sequences,
      or with antisense oligonucleotides, (2) immunotherapy through passive or active
      immunization protocols, and (3) inhibition of p21(ras) farnesylation either by
      inhibition of farnesyl transferase or synthesis inhibition of farnesyl moieties.

PMID- 10895052
TI  - Antagonism of nitrous oxide antinociception in mice by intrathecally administered
      antisera to endogenous opioid peptides.
AB  - Previously it was demonstrated that nitrous oxide antinociception in the mouse
      abdominal constriction test is mediated by kappa-opioid receptors. Since nitrous
      oxide is thought to cause the neuronal release of endogenous opioid peptide to
      stimulate opioid receptors, this study was designed to identify the opioid
      peptides involved, especially in the spinal cord, by determining whether nitrous
      oxide antinociception can be differentially inhibited by intrathecally (i. t.)
      administered antisera to different opioid peptides. Male NIH Swiss mice were
      pretreated i.t. with rabbit antisera to opioid peptides then exposed 24 h later
      to one of three different concentrations of nitrous oxide in oxygen. Dose
      response curves constructed from the data indicated that the antinociceptive
      effect of nitrous oxide was significantly antagonized by antisera to various
      dynorphins (DYNs) and methionine-enkephalin (ME), but not by antiserum to beta
      endorphin (beta-EP). The AD(50) values for nitrous oxide antinociception were
      significantly elevated by antisera to DYNs and ME but not beta-EP. These findings
      of this study support the hypothesis that nitrous oxide antinociception in the
      mouse abdominal constriction test involves the neuronal release of DYN and ME in
      the spinal cord.

PMID- 10895053
TI  - Effects of capacitative calcium entry on agonist-induced calcium transients in
      A7r5 vascular smooth muscle cells.
AB  - OBJECTIVE: The purpose of this study was to evaluate the contribution of
      capacitative calcium influx to intracellular calcium levels during agonist
      induced stimulation of vascular smooth muscle cells. METHODS: Aortic vascular
      smooth muscle cells (A7r5) were loaded with Indo-1 and intracellular calcium
      transients were measured. Cells were challenged with either arginine vasopressin
      (0. 5 microM) or thapsigargin (1 microM). Lanthanum (1 mM) was used to block
      capacitative calcium influx through store-operated channels. Calcium traces were
      analyzed for basal, peak and plateau responses. Recordings were derivatized and
      integrated to gain additional information. Nonlinear regression provided a time
      constant that describes restoration of ionic equilibrium involving both
      sequestration and extrusion pathways. RESULTS: Stimulation of cells with
      thapsigargin produced a non-L-type calcium influx that was attenuated by
      lanthanum. Cells excited with vasopressin exhibited a rapid calcium increase
      followed by a gradual decrease to a plateau level. Lanthanum pretreatment prior
      to stimulation caused no significant change in baseline, peak or plateau calcium
      levels as compared to control. Lanthanum caused no significant change in maximal
      calcium release rate, calcium integrals or time constant as compared to control.
      CONCLUSIONS: Capacitative calcium entry can occur in vascular smooth muscle
      cells, but does not appear to contribute significantly to the vasopressin
      response.

PMID- 10895054
TI  - Phosphatidylethanol stimulates calcium-dependent cytosolic phospholipase A(2)
      activity of a macrophage cell line (RAW 264.7).
AB  - The synthesis of inflammation mediators produced from arachidonic acid is
      regulated primarily by the cellular concentration of free arachidonic acid. Since
      intracellular arachidonic acid is almost totally present as phospholipid esters,
      the concentration of intracellular arachidonic acid is primarily dependent on the
      balance between the release of arachidonic acid from membrane phospholipids and
      the uptake of arachidonic acid into membrane phospholipids. Cytosolic
      phospholipase A(2) is a calciumdependent enzyme that catalyzes the stimulus
      coupled hydrolysis of arachidonic acid from membrane phospholipids. Following
      exposure of macrophages to various foreign or endogenous stimulants, cytosolic
      phospholipase A(2) is activated. Treatment with these compounds may also
      stimulate phospholipase D activity, and, in the presence of ethanol,
      phospholipase D catalyzes the synthesis of phosphatidylethanol. A cell-free
      system was used to evaluate the effect of phosphatidylethanol on cytosolic
      phospholipase A(2) activity. Phosphatidylethanol (0.5 microM) added to 1-stearoyl
      2-[(3)H]-arachidonoyl-sn-glycero-3-phosphocholine vesicles stimulated cytosolic
      phospholipase A(2) activity. However, high concentrations (20-100 microM) of
      phosphatidylethanol inhibited cytosolic phospholipase A(2) activity. Phosphatidic
      acid, the normal phospholipase D product, also stimulated cytosolic phospholipase
      A(2) activity at 0.5 microM, but had an inhibitory effect on cytosolic
      phospholipase A(2) activity at concentrations of 50 and 100 microM. Ethanol (20
      200 mM), the precursor of phosphatidylethanol, added directly to the assay did
      not alter cytosolic phospholipase A(2) activity. These results suggest that
      phosphatidylethanol alters the physical properties of the substrate, and at lower
      concentrations of anionic phospholipids the substrate is more susceptible to
      hydrolysis. However, at high concentrations, phosphatidylethanol either reverses
      the alterations in physical properties of the substrate or phosphatidylethanol
      may be competing as the substrate. Both interactions may result in lower
      cytosolic phospholipase A(2) activity.

PMID- 10895055
TI  - Age-associated changes in interferon-gamma and interleukin-4 secretion by
      purified human CD4+ and CD8+ T cells.
AB  - Aging is associated with a decline in immune function. Interferon-gamma (IFN
      gamma) and interleukin-4 (IL-4), two important immune deviation-related
      cytokines, are mainly produced by type 1 and type 2 T cells, respectively. To
      investigate the age-associated changes in the secretion of these two cytokines,
      20 elderly and 20 young subjects fulfilling the SENIEUR protocol were enrolled.
      The ratios of CD4+ to CD8+ T cells were not different between the two age groups.
      The CD4+ and CD8+ T cells were purified by a magnetic cell sorting system, and
      then activated by concurrent anti-CD3 and anti-CD28 stimulation. The released
      cytokines were determined by ELISA. Both the CD4+ and the CD8+ T cells of the
      elderly individuals secreted a significantly larger amount of IFN-gamma after
      activation. Profound IL-4 production by CD8+ T cells was observed in the older
      subjects compared with that of the young subjects. These data suggested that age
      associated decrease in immunity may be related to an imbalance in the secretion
      of immune deviation cytokines. The number of IL-4-secreting CD8+ T cells (T
      cytotoxic 2) rose significantly in the older individuals. Our design also
      provided a useful way to differentiate the T cell subsets secreting the same
      cytokine, such as IFN-gamma-producing T helper 1 and T cytotoxic 1 cells.

PMID- 10895056
TI  - Differential apoptosis effects of primate lentiviral Vpr and Vpx in mammalian
      cells.
AB  - The growth inhibitory effects of Vpr and Vpx are species- and cell type
      dependent. HIV-1, HIV-2 and SIV Vpr are primarily cytostatic in mammalian cells
      and HIV-1 Vpr has been reported to induce apoptosis in human cells. Our previous
      studies have shown that HIV-1, HIV-2 and SIV Vpr and Vpx have differential
      cytostatic and cytotoxic effects in the yeast cells [Zhang et al.: Virology,
      230:103-112; 1997]. Here, we further examined the apoptosis function of HIV-1 Vpr
      in different species of mammalian cells and investigated if other primate
      lentiviral Vpr and Vpx exert similar functions. Our results show that none of the
      primate lentiviral Vpr or Vpx we tested induces apoptosis in nonhuman species of
      mammalian cells. However, HIV-1 Vpr, but not HIV-2 or SIV Vpr and/or Vpx, induced
      apoptosis in different types of human cell lines. Further, the apoptotic effect
      of HIV-1 Vpr can be distinguished from that of the human interferon-gamma, a
      known proapoptotic protein, that HIV-1 Vpr shows little to no paracrine and/or
      bystander effect. When coexpressed with Bcl-2 or Bcl-X(L), the apoptotic effect
      of HIV-1 Vpr became markedly attenuated. These results indicate that the
      apoptotic effect of HIV-1 Vpr is species-dependent and is intracellularly
      modulated by the Bcl-2 family of proteins. Our study also suggests that the
      proapoptotic function of HIV-1 Vpr is developmentally associated with human but
      not nonhuman primate species.

PMID- 10895057
TI  - Molecular characterization of a hepatitis E virus isolate from Namibia.
AB  - Hepatitis E virus (HEV) causes sporadic and epidemic acute viral hepatitis in
      many developing countries. In Africa, hepatitis E has been documented by virus
      detection (reverse transcriptase polymerase chain reaction, RT-PCR) in Egypt,
      Chad, Algeria, Morocco and Tunisia. Cases of presumptive hepatitis E also have
      been documented by detection of antibody to HEV in the Sudan, Kenya, Ethiopia,
      Somalia, Djibouti and South Africa. Recently, we reported the recovery of 9
      isolates of HEV from feces collected during an outbreak of jaundice in Namibia.
      These specimens were stored frozen for many years at the South African Institute
      for Medical Research awaiting new methods to determine the etiology of jaundice.
      HEV genomic sequences were detected by antigen-capture RT-PCR with primers that
      amplified 2 independent regions of the HEV genome (ORF-2 and ORF-3). To further
      characterize the HEV 83-Namibia isolates, we determined the nucleotide (nt)
      sequence of the 3' end of the capsid gene (296 of 1, 980 nt in ORF-2) and ORF-3
      for 1 isolate. The capsid gene sequence shared 86% identity with the prototype
      Burma strain and up to 96% identity with other African strains at the (nt) level,
      and 99% identity with Burma or other Africa strains at the amino acid level. A
      188 (nt) fragment amplified from ORF-3 was also highly homologous to other HEV
      but was too short for meaningful comparison. Phylogenetic analysis indicated that
      HEV 83-Namibia is closely related to other African isolates, and differs from
      Burmese, Mexican and Chinese HEV. These data link the HEV causing the 1983
      Namibia outbreak to more recent HEV transmission in northern and sub-Saharan
      Africa, suggesting this subgenotype of HEV is firmly established throughout the
      continent.

PMID- 10895058
TI  - Prognosis and surgical treatment of gastric cancer invading the pancreas.
AB  - The clinicopathologic characteristics of gastric cancer invading the pancreas
      have not been determined. Gastrectomy was performed in 282 patients with gastric
      cancer invading adjacent organs at the Department of Surgery II, Kyushu
      University Hospital, between 1970 and 1987, and patient data were retrospectively
      analyzed using univariate and multivariate analyses. Of these patients, 150
      (53.2%) had tumors invading the pancreas and 132 had tumors invading adjacent
      organs other than the pancreas. In both groups, the undifferentiated tissue type
      with infiltrative growth, lymphatic involvement and lymph node metastasis was
      common. In cases of pancreas invasion, the extent of lymph node metastasis was
      more severe, vascular involvement was more frequent and the rate of concomitant
      liver metastasis was higher. The survival time of the patients with pancreas
      invasion was shorter compared to patients with cancer invading other organs, and
      pancreas involvement was one of the independent factors predicting a poor
      prognosis. With respect to surgical treatment of gastric cancer invading the
      pancreas, the prognosis was better for cases treated with curative surgery and
      pancreas resection. Of 39 patients treated with partial resection of the
      pancreas, the tumor had invaded only the capsule of the pancreas in 18 and the
      pancreas in the other 21. Pancreas-invasive gastric cancer cells are likely to
      advance via lymphatic and vascular routes and survival time is shorter, but
      curative resection can improve the survival rate, and perioperative treatment
      should be appropriately designed.

PMID- 10895059
TI  - Effects of three cytokine regimens on hematologic recovery and progenitor cell
      mobilization after high-dose cyclophosphamide, etoposide, and cisplatin.
AB  - The aim of this study was to compare both the effects on hematologic recovery and
      circulating progenitor cell mobilization and the toxicity of three cytokine
      regimens administered after high-dose non-myeloablative chemotherapy with
      cyclophosphamide 5 g/m(2), etoposide 1.5 g/m(2) and cisplatin 150 mg/m(2). Thirty
      five consecutive patients were non-random sequentially allocated to one of three
      treatment groups: (1) granulocyte colony-stimulating factor alone (n = 15); (2)
      granulocyte-macrophage colony-stimulating factor alone (n = 10), and (3)
      sequential interleukin-3 and granulocyte-macrophage colony-stimulating factor (n
      = 10). Neutrophil recovery in group 1 was significantly hastened as compared to
      the two other groups (median 2 days, p < 0.005), while no significant differences
      were observed between groups 2 and 3. CD34+ cells peaked about 2 days earlier in
      group 1 compared to the other groups (p = 0.0001), whereas the median peak value
      of CD34+ cells was similar in the three groups. In all patients, the toxicity
      related to cytokine administration was low and easily manageable with
      nonsteroidal anti-inflammatory drugs.

PMID- 10895060
TI  - Weekly 24-hour infusion of high-dose 5-fluorouracil plus folinic acid in
      combination with mitomycin C for the treatment of advanced gastric cancer.
AB  - PURPOSE: This study was performed to investigate the activity and safety of high
      dose 5-fluorouracil (5-FU) given as a weekly 24-hour infusion in combination with
      folinic acid plus mitomycin C in patients with advanced gastric cancer. PATIENTS
      AND METHODS: Chemonaive patients with locally advanced inoperable, recurrent or
      metastatic gastric cancer were treated with 15 mg/m(2) i.v. mitomycin C as bolus
      on day 1 of a 7-week cycle followed by a 2-hour infusion of folinic acid (500
      mg/m(2)) and a 24-hour infusion of 5-FU (2,600 mg/m(2)) given on days 1, 8, 15,
      22, 29, and 36 as outpatient treatment. RESULTS: Thirty evaluable patients
      (median age 58 years and median ECOG performance status 1) received 1-4 cycles
      (median 3). 53% of the patients had liver metastases. Treatment-related toxicity
      was low with 10% of patients experiencing diarrhea >/=grade 3, 3% mucositis grade
      3 and 3% nausea grade 3 (CTC). Hematological toxicity was mild with 13%
      thrombopenia grade 3 and no leukopenia grade 4. Eleven patients achieved a
      partial remission (major response rate 37%; 95% confidence interval 22-53%).
      Median time to progression was 5 months and median overall survival time was 7
      months. CONCLUSION: This regimen is a well-tolerated outpatient treatment for
      patients with advanced gastric cancer with efficacy being comparable to other
      chemotherapy protocols.

PMID- 10895061
TI  - Body mass index determines the success of lymph node dissection and predicts the
      outcome of gastric carcinoma patients.
AB  - We tried to determine the role of the body mass index (BMI) on the extent of
      lymph node dissection in gastric cancer surgery. Seven hundred and eighty-seven
      patients with gastric carcinoma were reviewed. Ninety-two (11%) patients exceeded
      the upper limit of the optimum BMI. Significantly fewer lymph nodes were removed
      following D2 (p = 0.002) and >/=D3 (p = 0.023) dissections, and the lymph node
      ratio was significantly (p = 0.0383) higher in overweight patients. The
      recurrence-free survival was significantly (p = 0.0297) shorter in T2/T3 cases
      with high BMI, and BMI (relative risk 1.85) became an independent prognostic
      factor in multivariate analysis. Higher BMI hampers regional lymph node
      dissection in gastric cancer patients and became an independent predictor of
      disease recurrences in T2/T3 gastric cancers.

PMID- 10895062
TI  - Carboplatin-gemcitabine treatment of patients with transitional cell carcinoma of
      the bladder and impaired renal function.
AB  - INTRODUCTION: Bladder cancer is a frequently occurring tumour in Spain and
      usually affects elderly patients with renal impairment. The development of new
      combination therapies for such patients is thus of vital importance. PATIENTS AND
      METHODS: Between 1997 and 1998, 17 patients with locally advanced non-surgical or
      metastatic bladder tumours were treated at our centres. Treatment consisted of
      1,000 mg/m(2) of gemcitabine administered on days 1 and 8, and carboplatin (area
      under the concentration curve = 5) on day 1, every 21 days. RESULTS: The mean age
      of the patients [4 females (26%) and 13 males] was 69 years (range: 54-78 years).
      The average Karnofsky performance status was 80% (range: 50-100%). Mean
      creatinine clearance was 45.4 ml/min (range: 21-55 ml/min). There were 2 complete
      responses, 7 partial responses (RO: 56%; range 31-81%), 6 patients had stable
      disease and 1 disease progression. Haematological toxicities were as follows:
      grade I anaemia in 2 patients, grade III in 3; grade I granulocytopenia in 2
      patients, grade III-IV in 4 patients; grade III thrombocytopenia in 3 patients.
      Toxic death occurred in the course of one grade IV neutropenic event. Non
      haematological toxicities were as follows: grade I-II vomiting in 3 patients and
      grade III in 1. One patient had grade III hepatic toxicity. One patient had grade
      III renal toxicity, and 3 patients grade II alopecia. CONCLUSIONS: The above
      mentioned treatment has low toxicity, is easy to administer and offers promising
      results in this group of patients.

PMID- 10895063
TI  - Contemporaneous bilateral forearm triceps metastases from adenocarcinoma of the
      lung.
AB  - Haematogenous skeletal muscle metastases from non-small-cell lung cancer (NSCLC)
      are rare, and are even more uncommonly observed bilaterally. Usually, NSCLC
      metastasizes to the liver, adrenal glands, lung, bone, central nervous system and
      kidney. We report a case of a long-surviving patient with contemporaneous
      histologically proven bilateral muscle metastases in the right and left forearm
      triceps, from adenocarcinoma of the lung.

PMID- 10895064
TI  - Serum p53 autoantibodies in the follow-up of head and neck cancer patients.
AB  - p53 autoantibodies (AAB) are a fairly new serological parameter in patients with
      malignancies. Although the actual mechanism of how they develop is still unclear,
      it seems that these AAB could be of prognostic relevance. Very few studies
      demonstrated the usefulness of p53 AAB in the follow-up of cancer patients. In
      this study, 109 patients with head and neck cancer were investigated using an
      ELISA for the presence of p53 AAB in their serum and were followed-up for at
      least 36 months. In 21 of the cancer patients, p53 serum AAB were detected. In
      5/21 p53-seropositive AAB patients, a correlation with the clinical course was
      observed. Sixteen of the p53-positive patients did not show any significant AAB
      titer changes during the follow-up, and no significant correlation with the
      clinical course was seen. According to these results, the clinical value of p53
      AAB in the follow-up of patients with head and neck cancer seems to be limited.

PMID- 10895065
TI  - Diffuse mode of tumor cell invasion and expression of mutant p53 protein but not
      of p21 protein are correlated with treatment failure in oral carcinomas and their
      metastatic foci.
AB  - Lack of control of metastatic foci is the most prevalent cause of death in
      patients with oral carcinomas, and it is important for tumor control to identify
      the factors that predispose patients to death. In the present study, we examined
      225 patients with oral squamous cell carcinoma and investigated the
      immunohistopathological characteristics of 43 tumors that led to death, comparing
      them with those of the non-lethal tumors. In the 43 patients, lack of control of
      the primary site, lymph node and distant metastatic tumors were noted in 20, 18
      and 16 patients, respectively. The mode of tumor cell invasion was closely
      correlated with death. The diffuse invasion modes of grades 4C and 4D were
      observed in 15 (34.9%) of the 43 tumors with a poor outcome and in 35 (19.2%) of
      the 182 controlled tumors (p < 0.02). The expression of p53 was highly correlated
      with death. Of the tumors with poor prognosis, p53 protein was expressed in 32
      tumors (76.2%). However, p53 protein expression was observed in 52.7% of the
      tumors with good prognosis (p < 0.02). In contrast, the expression of p21 protein
      in the well-controlled tumors (30.4%) was almost equal to that of the 43 lethal
      tumors (26.2%). Compared with the ratios of local recurrence, metastases and
      their treatment failures in the p53-negative grade 1 and 2 tumors, those in the
      mutant p53-positive grade 3, 4C and 4D tumors were mostly high. These results
      indicate that measuring p53 protein expression and evaluating the mode of tumor
      cell invasion are important for oral carcinoma therapy because the expression of
      mutant p53 protein and the diffuse modes of tumor cell invasion indicate a
      predisposition toward a poor prognosis.

PMID- 10895066
TI  - Frequency of microsatellite instability inBreast cancer determined by high
      resolution fluorescent microsatellite analysis.
AB  - In breast cancer, the rates of positivity for microsatellite instability (MSI),
      vary greatly in the literature. Using high-resolution fluorescent microsatellite
      analysis (HFRMA), we studied microsatellite alterations in 75 patients with
      sporadic breast cancer. In this system, several devices were prepared to improve
      reproducibility of polymerase chain reaction products, migration accuracy of
      electrophoresis, and characteristics of the detection system. Precise and
      objective analyses of microsatellite alterations are made feasible using HRFMA.
      Seven of the 75 cases were judged to be positive for MSI, the rate of positivity
      being 9. 3%. This rate is relatively low compared to the data in the literature.
      All the microsatellite changes observed in this system can be classified into two
      types: type A with relatively small changes in microsatellite sequences observed
      in limited loci and type B with drastic and widely dispersed changes. The former
      was thought to be connected to abnormal activity in DNA mismatch repair (MMR).
      Among the 7 cases, 6 (8.0%) had type A alterations, which means that the tumors
      may have an abnormal MMR activity. Application of precise and objective systems
      for microsatellite analysis is expected to be clinically useful to detect
      patients at high risk for cancers.

PMID- 10895067
TI  - Genetic aberrations detected by comparative genomic hybridization in ovarian
      clear cell adenocarcinomas.
AB  - Genetic abnormalities were detected by comparative genomic hybridization (CGH) in
      12 ovarian clear cell adenocarcinomas. DNA sequence copy number abnormalities
      (CNAs) occurring in more than 20% of the cancers included increased copy numbers
      of 8q11-q13, 8q21-q22, 8q23, 8q24-qter, 17q25-qter, 20q13-qter and 21q22-qter and
      reduced copy numbers of 19p. Increases in copy numbers of 8q11-q13, 8q21-q22,
      8q23 and 8q24-qter occurred more frequently in disease-free patients than in
      recurrent/non-surviving patients (p < 0.05). However, increases in copy numbers
      of 17q25-qter and 20q13-qter occurred more frequently in recurrent/non-surviving
      patients than in disease-free patients (p < 0.05). Furthermore, increases in copy
      numbers of 17q25-qter and 20q13-qter occurred together (p < 0.05). Additionally,
      there were negative correlations between increases in copy numbers of 8q21-q22
      and 17q25-qter, and between 8q21-q22 and 20q13-qter (p < 0.05). It appears that
      ovarian clear cell adenocarcinomas can be classified into two subtypes, one being
      cancer with an increase in copy numbers of 8q and the other being cancer with
      increases in copy numbers of 17q25-qter and 20q13-qter.

PMID- 10895068
TI  - HLA-DRB genotypes in Japanese patients with renal cell carcinoma.
AB  - OBJECTIVES: Several clinical features, such as the spontaneous regression of some
      renal cell carcinoma (RCC) metastases after nephrectomy, suggest immune
      involvement in tumor destruction. PATIENTS AND METHODS: We investigated the role
      of genetic variation at the HLA class II loci in RCC by analyzing the HLA-DR
      antigen and HLA-DRB1, DRB3, DRB4 and DRB5 alleles in 55 patients using the
      polymerase chain rection. RESULTS: No statistically significant differences were
      observed in the frequency of the HLA-DR antigen or HLA-DRB3, DRB4, or DRB5 genes
      between the patients and a healthy control group. On the other hand, the HLA
      DRB1*0403 and *1202 alleles were significantly more frequent in the patients than
      in the controls (p < 0.001 and p < 0.01, respectively). CONCLUSION: RCC might be
      linked to these two alleles in Japanese patients.

PMID- 10895069
TI  - Bcl-2 expression in cholangiocellular carcinoma is inversely correlated with
      biologically aggressive phenotypes.
AB  - bcl-2 is known to play a crucial role in modulating carcinoma progression as well
      as in inhibiting apoptosis. However, its expression and clinical significance for
      cholangiocellular carcinoma (CCC) remains unclear. In the present study, we
      immunohistochemically investigated bcl-2 expression in 41 CCC. Thirteen cases
      (31.7%) were classified as bcl-2 positive, because more than 10% of the carcinoma
      cells expressed bcl-2. The expression of bcl-2 was inversely related to lymph
      node metastasis, vascular invasion, perineural invasion, the Ki-67 labeling
      index, aberrant p53 expression and the incidence of apoptotic cells. Furthermore,
      well or moderately differentiated carcinoma more frequently expressed bcl-2.
      These results suggest that downregulation of bcl-2 expression is strongly linked
      to highly biologically aggressive phenotypes of CCC.

PMID- 10895070
TI  - Expression and prognostic role of cyclin-dependent kinase 1 (cdc2) in
      hepatocellular carcinoma.
AB  - The expression of cyclin-dependent kinase 1 (cdc2), cyclin A and cyclin B1 was
      immunohistochemically studied in 101 hepatocellular carcinomas (HCC). cdc2
      overexpression was directly related to advanced stage, portal invasion,
      intrahepatic metastasis, poor differentiation, high alpha-fetoprotein level,
      large size, high Ki-67 labeling index and poor prognosis. Cyclin A and B1
      overexpression showed similar tendency to that of cdc2, but they were not
      recognized as independent prognostic factors by multivariate analysis. These
      findings suggest that cdc2 plays the most crucial role of the G2/M modulators in
      cell cycle progression and cell proliferation of HCC and significantly predicts
      the recurrence of this carcinoma.

PMID- 10895071
TI  - Prevention of metastasis by a polyamine synthesis inhibitor in an animal bone
      metastasis model.
AB  - In order to better understand the development of skeletal metastases, we
      developed an appropriate animal model, as the natural progression of metastases
      in humans cannot be studied on the cellular level. In this study, we established
      a new animal model which developed bone metastasis in a bone grafted
      subcutaneously. C57BL/6 mice, which had received a bone (femur or tibia)
      transplanted in the dorsal subcutis, were injected with B16 melanoma cells into
      the left heart ventricle. Metastasis was found in approximately 70% of the
      extraskeletal bones. Using this model, the antimetastatic effect of a polyamine
      synthesis inhibitor was investigated. Inhibitors of the polyamine biosynthetic
      pathway have received considerable attention for their potential use in the
      treatment of cancer as they are responsible for the greatly increased production
      of the polyamines putrescine, spermidine, and spermine. A polyamine synthesis
      inhibitor, methylglyoxal-bis(cyclopentylamidinohydrazone) MGBCP, was investigated
      for its inhibitory effects on bone metastases. MGBCP (20 mg/kg) was administered
      intraperitoneally every day for 4 weeks and demonstrated strong inhibitory
      effects on bone metastases. MGBCP inhibited angiogenesis in the transplanted bone
      and the growth of B16 melanoma cells, thus suggesting a preventive mechanism in
      bone metastasis. No remarkable adverse effects of MGBCP were observed in any
      animal throughout the experimental period. Our results indicate that MGBCP has a
      strong potential for use as an anti-metastatic drug.

PMID- 10895072
TI  - High percentage of false-positive results of cytokeratin 19 RT-PCR in blood: a
      model for the analysis of illegitimate gene expression.
AB  - Cytokeratin 19 (CK19) RT-PCR is widely used in order to detect circulating tumor
      cells in peripheral blood and bone marrow. However, increasing amounts of
      information support the fact that it is also associated with a high percentage of
      false-positive results. In our study, we not only managed to demonstrate the
      significant limitations of this method, but were also able to clarify the reasons
      behind these limitations. We developed a completely novel RT-PCR for CK19 and
      sequenced an intron at nucleotide (nt) 980 of the CK19 mRNA to exclude DNA
      contamination. Tumor dilution experiments were performed in order to analyze the
      specificity and sensitivity of the method. Control experiments using the blood of
      healthy donors were performed. Tumor cell dilution experiments gave a detection
      limit of one tumor cell. If tumor cells were mixed with an equal volume of pure
      mononuclear cells, the detection limit was 1 tumor cell in 10(5) mononuclear
      cells. RT-PCR of mononuclear cells from healthy blood donors gave false-positive
      results in 29% of the cases. We conclude that a significant decrease in the
      sensitivity of CK19 RT-PCR occurs if it is performed in blood cells and that the
      illegitimate CK19 gene expression in normal cells can lead to false-positive
      results. These limitations have to be taken into account if RT-PCR is to be used
      for the detection of tumor cells either in blood or in bone marrow in clinical
      practice.

PMID- 10895073
TI  - Effects of Ba(2+) on norepinephrine-induced contraction of rat thoracic aorta in
      vitro.
AB  - The aim of this study was to examine the effect of exogenously applied BaCl(2) on
      the norepinephrine-induced contraction of the rat thoracic aorta. Exogenously
      applied BaCl(2) (0.3-1 mmol/l) slightly elevated the norepinephrine-induced
      sustained contraction of the rat thoracic aorta in the absence of nicardipine (1
      micromol/l). In the aortic preparation pretreated with nicardipine (1
      micromol/l), exogenous BaCl(2) (0.1-3 mmol/l) did not elevate the norepinephrine
      induced sustained contraction, but the high concentration of BaCl(2) (10 mmol/l)
      slightly inhibited the norepinephrine-induced tone. In a Ca(2+)-free Krebs bi-
      carbonate solution (KBS) containing norepinephrine (1 micromol/l) or a Ca(2+)
      free K(+)-rich (60 mmol/l) KBS, exogenously applied BaCl(2) (1-30 mmol/l) caused
      a sustained contraction of the rat thoracic aorta, and this sustained contraction
      was completely inhibited by nicardipine (1 micromol/l). Exogenous CaCl(2) (0.1-3
      mmol/l) also caused a sustained contraction of the aortic preparation in a Ca(2+)
      free KBS containing norephinephrine (1 micromol/l), but such a sustained
      contraction was partly inhibited by nicardipine (3 micromol/l). These results
      indicate that Ba(2+) elevates the norepinephrine-induced tone of the rat isolated
      thoracic aorta by permeating voltage-dependent Ca(2+) channels in the absence of
      nicardipine, but that Ba(2+) has a minor modification on the norepinephrine
      induced sustained contraction of the nicardipine-pretreated preparation.

PMID- 10895074
TI  - Assessment of affinities of propranolol and bopindolol to membranes from COS-7
      cell transiently transfected with beta-1- and beta-2-adrenoceptors using a
      radioligand-binding assay method.
AB  - This study was performed to assess the affinities of propranolol, bopindolol, its
      two metabolites (18-502, 20-785), pindolol, metoprolol, and atenolol to beta(1)-
      and beta(2)-adrenoceptor (beta(1)- and beta(2)-AR) subtypes using the membranes
      of COS-7 cells transiently expressing beta(1)- and beta(2)-AR subtypes.
      Radioligand-binding assays were performed and the results were compared with
      those (pKi or pA(2) values) obtained from the membrane-enriched fractions from
      the rat heart, cerebral cortex, bovine heart, tracheal smooth muscle or guinea
      pig heart muscle. The pKi values of propranolol, bopindolol, its two metabolites,
      atenolol, pindolol and metoprolol to beta(1)-AR subtypes obtained from COS-7 cell
      membranes were 9.02 +/- 0.04, 7.44 +/- 0.12, 9.38 +/- 0.31, 6. 65 +/- 0.16, 5.55
      +/- 0.14, 8.17 +/- 0.15 and 5.99 +/- 0.13, respectively. The rank order of pKi
      values for these agents to beta-(2)-ARs in COS-7 cell membranes was the same as
      that of beta(1)-ARs. In addition, good correlations were observed between pKi
      values of homogenates from various tissues and those of transfected COS-7 cell
      membranes to beta(1)- and beta(2)-ARs. Although good correlations were also
      observed between pA(2) values obtained from tracheal smooth muscle (beta(2)-ARs)
      and pKi values obtained from transfected COS-7 cell membranes to beta(2)-ARs, low
      correlation coefficient values to beta(1)-ARs were observed, however. In
      conclusion, these results suggested that binding characteristics of (3)H-CGP
      12177 to beta-AR subtypes in these membranes from transfected COS-7 cells are
      similar to those from membrane fractions of various tissues.

PMID- 10895075
TI  - Thrombin stimulates pertussis toxin-sensitive and -insensitive GTPase activities
      and ADP-ribosylation of G(i) in human neuroblastoma SH-EP.
AB  - Kinetic interaction between thrombin receptor and G proteins was investigated in
      human epithelial neuroblastoma cell line, SH-EP. In these cells, both alpha
      thrombin and SFLLRNP (one-letter amino-acid code) stimulated GTPase activity and
      enhanced cholera toxin-catalyzed ADP-ribosylation of G(i2) in a concentration
      dependent manner. Basal GTPase activity was attenuated by pertussis toxin
      treatment by 35%, however, agonist stimulation was preserved significantly. These
      results together indicated that thrombin receptor simultaneously activates G(i2)
      and PTX-insensitive G protein(s).

PMID- 10895076
TI  - Differences in efficacy and Na(+) sensitivity between alpha(2B) and alpha(2D)
      adrenergic receptors: implications for R and R* states.
AB  - The ability of Na(+) ions to modulate coupling of alpha(2B)- and alpha(2D)
      adrenergic receptors to G proteins was investigated in isolated membranes from
      transfected PC12 and NIH 3T3 fibroblast cells. The initial rate of epinephrine
      stimulated [(35)S]GTPgammaS binding was higher for alpha(2D)-receptors (the rat
      homolog of the alpha(2A)-receptor) in both cell types, whereas both alpha(2B)-
      and alpha(2D)-receptor responses were higher in PC12 cell membranes. Pertussis
      toxin completely blocked agonist-stimulated binding. Graded increases in Na(+)
      caused a progressive loss of basal GTP binding, indicative of its ability to
      reduce the level of the active R* state of the receptor. This inhibitory effect
      of Na(+) was more pronounced in PC12/alpha(2B) than PC12/alpha(2D) membranes.
      Epinephrine-stimulated GTP binding in PC12/alpha(2B) membranes was also more
      sensitive to Na(+) inhibition than in PC12/alpha(2D) membranes. In saturation
      [(35)S]GTPgammaS binding studies, the presence of Na(+) reduced apparent GTP
      affinity, and its effect was greater in PC12/ alpha(2B) membranes, consistent
      with a greater reduction in the active R* conformation of the receptor. The
      higher efficacy of epinephrine at alpha(2D) receptors and their lesser
      sensitivity to Na(+) are both indicative of a more stable R* state. Together
      these results suggest that differences in the modulatory influence of Na(+)
      within a family of G(i)-coupled receptors may reflect differences in the
      stability of the active R* state.

PMID- 10895077
TI  - Antithyroid action of tamoxifen in the rat: in vivo and in vitro studies.
AB  - The influence of administration of tamoxifen (TAM) on thyroid metabolism was
      investigated. The potential action of TAM on iodine in the thyroid gland was
      evaluated by determination of the equilibrium constant of the charge transfer
      complex formed with molecular iodine and by computational studies. Adverse
      effects of TAM on thyroid function parameters were also investigated in female
      Wistar rats. Rats were treated for seven weeks with 5 mg/kg/day of TAM.
      Irrespective of the iodine content of the diet, administration of TAM led to
      goitre and a significant increase in levels of T4 and TSH. Similar results,
      albeit more marked, were observed after administration of an inhibitor of thyroid
      peroxidase. We also showed that TAM forms charge transfer complex with iodine (Kc
      = 876 liters/mol). We concluded that under our experimental conditions, TAM
      exerts antithyroid activity from an action on thyroid peroxidase. Nevertheless,
      when the exogenous iodine contribution is restricted, TAM may sequester iodine in
      the form of charge transfer complexes, thereby enhancing hypothyroidism.

PMID- 10895078
TI  - Effects of propylthiouracil treatment on antioxidant activities in blood of toxic
      multinodular goiter patients.
AB  - Erythrocyte, serum and plasma antioxidant activities and the effects of
      propylthiouracil (PTU) treatment on these activities were studied in patients
      with toxic multinodular goiter. The activities of the erythrocyte antioxidant
      enzymes (glucose-6-phosphate dehydrogenase, catalase, Cu/Zn-superoxide dismutase,
      selenium (Se)-dependent glutathione peroxidase and glutathione reductase) and the
      levels of erythrocyte Se, serum ceruloplasmin and plasma malondialdehyde were
      significantly higher while serum vitamin E, plasma vitamin C and plasma Se were
      lower in hyperthyroid patients. PTU treatment, not for 1 but for 3 months caused
      a partial reversal of antioxidant activities to euthyroid levels. It is suggested
      that alterations in blood antioxidant activities following PTU treatment might be
      due to the antioxidant and/or antithyroid effect of this drug.

PMID- 10895079
TI  - M(2) and M(4) muscarinic receptor subtypes couple to activation of endothelial
      nitric oxide synthase.
AB  - In this report we studied coupling of M(2) and M(4) muscarinic acetylcholine
      receptors to activation of endothelial nitric oxide synthase (eNOS). Chinese
      hamster ovary cells that co-express the individual receptor subtypes and eNOS in
      a stable fashion were used as a model. Activation of eNOS was assayed by
      measuring increasing levels of cyclic GMP in admixed cells that contain guanylate
      cyclase. Activation of both M(2) or M(4) muscarinic receptors resulted in marked
      activation of eNOS, in a time- and concentration-dependent manner. The time
      course of the response exhibited a transient peak, followed by a sustained lower
      plateau. While the sustained phase was dependent on influx of extracellular
      calcium, the transient response showed dependency on both mobilization of
      intracellular calcium and extracellular influx.

PMID- 10895080
TI  - On the cardiac contractile, electrophysiological and biochemical effects of
      endothall, a protein phosphatase inhibitor.
AB  - Protein phosphatase inhibitors, e.g. cantharidin, exert positive inotropic
      effects in mammalian heart preparations. Endothall, a synthetic herbicide which
      is chemically related to cantharidin, inhibits protein phosphatase activities in
      mouse liver preparations. However, the cardiac effects of endothall have hitherto
      not been studied. In guinea pig papillary muscles, endothall (1-100 micromol/l)
      failed to affect force of contraction, whereas cantharidin (1-100 micromol/l)
      increased force of contraction maximally to 313.4 +/- 32% of control at 10
      micromol/l. In isolated guinea pig ventricular cardiomyocytes, endothall did
      neither change the free intracellular calcium concentration nor the amplitude of
      calcium current nor the phosphorylation state of regulatory phosphoproteins like
      phospholamban. In contrast, cantharidin (30 micromol/l) increased the free
      intracellular calcium concentration and the L-type calcium current to 149.6 +/-
      9% and to 157.6 +/- 12% of control, respectively. Furthermore, cantharidin (1-100
      micromol/l) augmented the phosphorylation of phospholamban maximally to 140.8 +/-
      7% of control. Nevertheless, in guinea pig ventricular homogenates, both
      endothall and cantharidin inhibited phosphatase activity with EC(50) values of
      1.92 and 0.32 micromol/l, respectively. Thus, in contrast to cantharidin,
      endothall failed to increase force of contraction, though it inhibited protein
      phosphatase activity. Clearly, endothall is not an appropriate tool to study the
      function of protein phosphatases in the mammalian heart.

PMID- 10895081
TI  - Decreasing cyclic GMP exerts similar positive functional effects on cardiac
      myocytes regardless of initial level.
AB  - We tested the hypothesis that lowering the level of cyclic GMP would have
      positive functional effects on isolated rabbit ventricular myocytes regardless of
      the basal cyclic GMP level. Cell shortening data were collected with a video
      detector; O(2) consumption data were obtained with a Clark electrode;
      intracellular cyclic GMP levels were obtained by radioimmunoassay. Data were
      obtained: (1) at baseline; (2) after the addition of 1H-[1,2,4]oxadiazolo[4, 3
      alpha]quinoxaline-1-one (ODQ) 10(-6) and 10(-4) mol/l, a selective soluble
      guanylyl cyclase inhibitor, and (3) after zaprinast 10(-6) mol/l, a cyclic GMP
      phosphodiesterase inhibitor, followed by ODQ 10(-6) and 10(-4) mol/l. We found
      that ODQ 10(-4) mol/l significantly decreased the cyclic GMP level from 493 +/-
      75 to 301 +/- 78 (fmol/100,000 myocytes) and increased percent shortening (Pcs,
      %; 4.9 +/- 0.3 vs. 5.8 +/- 0.6) and maximum rate of shortening (Rs, microm/s;
      58.7 +/- 5.7 vs. 73.6 +/- 4.9). Zaprinast significantly increased the cyclic GMP
      level from 419 +/- 140 to 599 +/- 241 and decreased Pcs (6.2 +/- 0.5 vs. 4.4 +/-
      0.4) and Rs (65.5 +/- 5.3 vs. 49.6 +/- 4.3). After zaprinast, ODQ 10(-4) mol/l
      decreased the cyclic GMP level to 439 +/- 139 and increased percent shortening
      and rate of shortening by a similar percentage compared to the non-zaprinast
      treated myocytes. We conclude that in rabbit ventricular myocytes, a reduction in
      the level of myocyte cyclic GMP increases myocyte function independent of the
      initial cyclic GMP level.

PMID- 10895082
TI  - Ureterointestinal anastomosis in orthotopic neobladders.
AB  - OBJECTIVE: This study reports our experience with a ureteroileal reimplantation
      technique based on the Leadbetter-Clarke method, which is used for orthotopic neo
      bladders, constructed preferably with the Camey II technique. METHODS: We carried
      out 114 ureteroileal reimplantations using this technique in 58 patients
      undergoing radical cystectomy and orthotopic neobladder reconstruction. The
      incidence of neobladder-ureteral stenosis and reflux were analyzed during the
      follow-up. RESULTS: During the mean follow-up of 31 months, the incidence of
      stenosis was 2.6% (3 ureteroileal implants, including 1 case of neoplastic
      stenosis). The incidence of slight-to-moderate reflux was 9.6% but did not cause
      any deterioration in renal function or an increased incidence of reflux-related
      pyelonephritis. CONCLUSION: This technique provided good functional results and a
      low incidence of complications, and may be recommended as a valid alternative to
      standard methods of creating ureterovesical anastomosis.

PMID- 10895083
TI  - Effect of increased intrareservoir pressure on upper urinary tract function in
      continent urinary diversion patients assessed by radioisotope renography.
AB  - To assess upper urinary tract function and determine an ideal continent reservoir
      capacity, we investigated the relationship between intrareservoir pressure and
      functional parameters using radioisotope renography. Forty-three patients for
      whom ileal reservoir construction was performed by Kock pouch (n = 33) or
      Hautmann's ileal neobladder (n = 14) approaches between November 1984 and
      September 1996 were studied. After the reservoir contents were catheterized,
      (99m)Tc-MAG 3 renoscintigraphy was carried out and time activity curves in the
      kidney (renogram) and reservoir (reservoirgram) were recorded, while saline
      solution was poured into the reservoir for monitoring of intrareservoir pressure.
      Three basic abnormal curves were noted in the excretory phase on renograms: a
      normal downward curve followed by an upward curve, a continuous upward curve
      associated with or without a sharp decline after the catheterization of the
      reservoir contents, and episodes of spike waves. Based on these curves, renograms
      were classified into five types: normal, high pressure, retention, obstruction,
      and reflux. Abnormal types were noted with 51 of 65 renal units (78.5%) in the
      Kock pouch group and 15 of 25 renal units (60.0%) in the neobladder group. This
      examination method may be useful for evaluating urodynamics in the upper urinary
      tract of patients with a continent ileal reservoir and provide data on adequate
      voiding volumes for the individual patient.

PMID- 10895084
TI  - How accurate is diagnostic imaging in determination of size and multifocality of
      renal cell carcinoma as a prerequisite for nephron-sparing surgery?
AB  - BACKGROUND: The indication for elective nephron-sparing surgery (NSS) in renal
      cell carcinoma (RCC) is under discussion in the urological literature. The main
      problem of NSS is the multifocality of RCC. The presented study was performed to
      asses the accuracy of pre- and intraoperative ultrasound (US), and computerized
      tomography (CT) in determination of tumor size and detection of multifocal
      lesions. MATERIALS AND METHODS: Tumor size was measured by preoperative US and CT
      and compared with the tumor diameters in gross sections of the neoplastic
      kidneys. Multifocality was determined by 3-mm step sectioning of the nephrectomy
      specimen, and the results were correlated with preoperative US and CT on the one
      hand, and the ex situ sonography of the nephrectomized kidney on the other hand.
      RESULTS: US and CT show similar results in the determination of the tumor size.
      In only 22.9%, preoperative US and CT were able to detect multifocal tumors. Ex
      situ sonography had a sensitivity of 40.0% and a specificity of 87.2% in this
      regard. CONCLUSIONS: In preparation for nephron-sparing surgery of renal cell
      carcinoma, neither preoperative routine imaging, nor intraoperative ultrasound
      can safely predict multifocal lesions of renal cell carcinoma.

PMID- 10895085
TI  - Urinary fibronectin levels in patients treated with intravesical bacillus
      Calmette-Guerin for superficial bladder cancer.
AB  - Intravesical bacillus Calmette-Guerin (BCG) has been shown to be an effective
      treatment for superficial transitional cell carcinoma (TCC) of the bladder, but
      the precise mechanism of action of BCG remains poorly understood. Fibronectin
      (FN), an important component of the extracellular matrix, has been found to play
      a role in BCG therapy. Some studies have shown that the soluble form of FN can
      compete efficiently with the matrix form of binding to the specific receptors on
      the bacteria and could consequently diminish the effect of BCG treatment. To
      evaluate a possible correlation between the urinary levels of FN and the efficacy
      of BCG therapy, we determined prospectively the urinary FN levels in 38 patients
      with TCC of the bladder and in 25 control subjects without malignancy matched for
      age and sex. All TCC patients were treated with transurethral tumor resection
      plus 6 weekly intravesical BCG instillations. After an average follow-up of 30
      months, 8 patients (21.1%) had recurrent tumors, while 30 (78.9%) were free of
      tumor after intravesical BCG therapy. Urinary levels of FN in cancer patients
      have been shown to be significantly higher than controls (p < 0.001). These
      elevated levels were not decreased significantly after the operation (p > 0. 05).
      It was also found that the mean urinary FN levels were not statistically
      significant between patients with recurrence and complete remission. The data
      suggest that BCG-bladder tumor cell binding is not influenced by soluble
      fibronectin and urinary FN may not be a ideal marker for selecting patients to
      BCG therapy.

PMID- 10895086
TI  - Serum-free coculture of stromal and epithelial cells from benign prostatic
      hyperplasia with keratinocyte growth factor.
AB  - We developed a serum-free coculture model of benign prostatic hyperplasia (BPH)
      to clarify whether stromal cells stimulate growth of epithelial cells from BPH
      tissues. Epithelial and stromal cells from freshly isolated BPH tissue were
      cultured separately in defined serum-free WAJC 404/RPMI 1640 medium supplemented
      with insulin, transferrin, selenium, hydrocortisone, bovine serum albumin,
      epidermal growth factor, basic fibroblast growth factor and keratinocyte growth
      factor. (3)H-Tdr incorporation into epithelial cells and stromal cells was used
      as a measure of proliferation. When epithelial cells were cocultured with stromal
      cells, (3)H-Tdr incorporation into epithelial cells was increased in comparison
      to that in epithelial cells cultured alone. Dihydrotestosterone significantly
      increased this effect. It is likely that the in vitro coculture model reported
      here will be useful for isolating and understanding stromal cell-derived
      paracrine growth factor(s).

PMID- 10895087
TI  - Spontaneous perirenal hematoma. A case report and review of literature.
AB  - Spontaneous perirenal hematoma (SPH) is a clinical entity that poses a diagnostic
      and therapeutic challenge. We report a case of SPH in an adult where the cause
      could not be determined at first presentation, even with computed tomography (CT)
      of the abdomen and angiography. He was under close follow-up, and it was only
      with a repeat CT scan after 3 months that a mass lesion in the kidney was
      identified as the underlying cause. We also present a review of the literature so
      that a logical approach can be adopted for this problem.

PMID- 10895088
TI  - Bronchogenic cyst. A rare differential diagnosis of retroperitoneal tumors.
AB  - Subdiaphragmatic bronchogenic cysts are rare, and those located retroperitoneally
      are exceptional. A review of the English-language literature revealed only 16
      reported cases. We describe an additional case of a retroperitoneal cyst
      presenting as an asymptomatic adrenal mass and discuss clinical, radiographic,
      surgical and pathological findings as well as its embryological background.

PMID- 10895089
TI  - Superselective microcoil embolization of a traumatic pseudoaneurysm of the
      cavernosal artery.
AB  - According to the literature, straddle injuries of the perineum may result in
      arteriosinusoidal fistula and secondary high-flow priapism. We report a case of a
      23-year-old man who developed a traumatic pseudoaneurysm of the cavernosal
      artery, secondary to straddle injury, and presented with painless priapism. It
      was treated successfully with superselective microcoil embolization and the
      priapism resolved.

PMID- 10895090
TI  - Embolization of a segmental renal artery pseudoaneurysm after partial nephrectomy
      in a solitary kidney.
AB  - Renal pseudoaneurysms are a well-documented complication following trauma or
      after percutaneous biopsy. When symptomatic, patients present with hematuria and
      deteriorating renal function. We present the case of a 62-year-old man who, due
      to development of a pseudoaneurysm, presented with gross hematuria 10 days after
      partial nephrectomy for a renal cell carcinoma in a single kidney. A segmental
      artery was embolized with stainless steel coils without significant loss of the
      limited renal vascularization.

PMID- 10895091
TI  - Massive hematuria in adults with Klippel-Trenaunay syndrome associated with
      vascular malformation of the bladder.
AB  - Although hematuria has been reported in children with Klippel-Trenaunay syndrome,
      it is a rare presentation in the adult population. Two cases of massive hematuria
      in adults with Klippel-Trenaunay syndrome are reported here. A unique feature was
      venous malformations of the bladder which were responsible for massive recurrent
      bleeding in 1 patient. The clinical presentation and management are discussed.
      Conservative endoscopic and arteriographic control seems to be appropriate as
      initial management in these patients.

PMID- 10895092
TI  - Nephrogenic adenoma of the bladder after intravesical bacillus Calmette-Guerin
      treatment.
AB  - A 60-year-old female patient was subjected to transurethral resection of
      transitional cell carcinoma of the bladder and was given intravesical bacillus
      Calmette-Guerin treatment for 6 weeks. The control cytoscopy performed after 6
      months revealed a polypoid lesion at the trigon and the lesion was resected. The
      pathological examination of the specimen showed no evidence of cancer but the
      presence of a metaplastic lesion that was nephrogenic adenoma.

PMID- 10895093
TI  - Photochemical inactivation of bacteria and HIV in buffy-coat-derived platelet
      concentrates under conditions that preserve in vitro platelet function.
AB  - BACKGROUND AND OBJECTIVES: A photochemical process has been tested for the
      inactivation of viruses and bacteria in buffy-coat derived platelet concentrates
      (BC PCs). MATERIALS AND METHODS: BC PCs in 35% CPD plasma and 65% platelet
      additive solution (PAS III) were exposed to photochemical treatment (PCT) with
      150 microM of the psoralen S-59 and a 3 J/cm(2) treatment with long-wavelength
      ultraviolet light (UVA, 320-400 nm). Platelet function was evaluated following
      PCT using a panel of in vitro assays. RESULTS: This PCT process was highly
      effective at inactivating gram-positive bacteria (Staphylococcus epidermidis,
      Staphylococcus aureus, Enterococcus faecalis) and gram-negative bacteria
      (Enterobacter aerogenes, Pseudomonas aeruginosa, Serratia marcescens). No viable
      bacteria were detected following PCT and 7 days of platelet storage while
      bacterial growth was detected in paired untreated control BC PCs. Complete
      inactivation of the gram-positive Bacillus cereus was achieved only in one of two
      replicate experiments with BC PCs. PCT was also highly effective for inactivation
      of human immunodeficiency virus HIV-1 in BC PCs inoculated with approximately
      10(6) tissue culture infectious doses per milliliter (TCID(50)/ml) of cell
      associated HIV-1. Rapid inactivation was observed with increasing UVA doses: with
      150 microM S-59 and a 1 J/cm(2) treatment of UVA, a reduction of 5.6+/-0.5 log
      TCID(50)/ml was achieved, and a reduction of >6.4 log TCID(50)/ml was achieved
      with 150 microM S-59 and a 3 J/cm(2) treatment of UVA. No physiologically
      relevant differences in platelet functions were found between the test and the
      control BC PCs during 7 days of storage. CONCLUSION: PCT with 150 microM S-59 and
      a 3 J/cm(2) UVA treatment does not adversely affect in vitro properties of BC PCs
      stored at 22 degrees C for 7 days. The PCT process inactivated bacteria and HIV-1
      inoculated into the BC PCs. These results extend the earlier reported efficacy of
      PCT apheresis PCs to BC PCs.

PMID- 10895094
TI  - Calibration of HCV working reagents for NAT assays against the HCV international
      standard. The Collaborative Study Group.
AB  - BACKGROUND AND OBJECTIVES: Five HCV RNA reference reagents, the Paul Ehrlich
      Institut (PEI) reference 75, the National Institute for Biological Standards and
      Control (NIBSC) reagent 96/586, the Central Laboratory of the Netherlands Red
      Cross Blood Transfusion Service (CLB) Pelispy HCV RNA run control S2001, the
      Istituto Superiore di Sanita (ISS) reagent 0498 and the CBER panel member No. 1,
      were calibrated against the WHO International Standard, 96/790. MATERIALS AND
      METHODS: The reference materials were calibrated in a collaborative study
      organised by NIBSC. Nineteen laboratories, using a range of qualitative and
      quantitative assays returned results. RESULTS: The concentrations of the reagents
      were: 25,000 IU/ml for the PEI material, 710 IU/ml for the NIBSC material 96/586,
      1,000 IU/ml for the CLB material, 1,700 IU/ml for the ISS material 0498 and 250
      IU/ml for the CBER panel member No. 1. CONCLUSIONS: The calibration of these five
      reference reagents for HCV RNA nucleic acid amplification technology (NAT) assays
      enables them to be used for standardisation and validation of assays. Such
      calibrants are essential for meeting the requirements of the European Medicinal
      Evaluation Agency (EMEA) for the testing of plasma pools and donations for HCV
      RNA for the release of blood products and the PEI requirements for the release
      testing of erythrocyte and thrombocyte concentrates.

PMID- 10895095
TI  - Natural history of haemoglobin levels in female blood donors with haemoglobin
      levels of 120-124 g/l at presentation.
AB  - BACKGROUND AND OBJECTIVES: In order to assess the effects of proposed changes to
      UK guidelines, female blood donors with venous haemoglobin (Hb) levels of 120-124
      g/l were followed up over a period of 18 months in order to assess frequency of
      attendance and ability to donate in relation to changes in Hb and red cell
      indices, and to determine the effects of inter-donation interval and iron
      supplementation on outcomes. MATERIALS AND METHODS: Venous samples were analysed
      using the Haemocue haemoglobinometer at each attendance, and a donation was taken
      if the Hb was 120 g/l or greater. Full blood counts were done on each sample
      using the Coulter Model T890. A postal questionnaire was used to elicit
      additional information, including use of iron supplements. RESULTS: The 392
      donors enrolled in the study gave 655 subsequent attendances, resulting in 468
      donations (1.5 donations/donor/year). Donors who subsequently had Hb <120 g/l had
      a tendency to lower initial mean corpuscular volume (MCV), but MCV could not be
      used as an indicator of future performance. 23% of donors reported use of iron
      supplements, but those donating 3 times or more were no more likely to use iron
      supplementation (20%). No statistical relationship was found between inter
      donation interval and ability to donate at subsequent attendances. CONCLUSIONS:
      Female donors with borderline Hb levels proved to be highly committed, with a
      donation rate of 1. 5/donor/year during the period of follow-up. MCV is not a
      useful predictor of ability to donate in the future. This subset of the donor
      population shows wide variation in Hb level over time, and this is largely
      independent of iron supplementation or inter-donation interval.

PMID- 10895096
TI  - Increased withdrawal volume per deposit for pre-operative autologous blood
      donation in adolescents.
AB  - OBJECTIVES: This study was undertaken to assess the feasibility, tolerance,
      haemodynamic and haematologic effects of an aggressive phlebotomy schedule for
      autologous blood donation (ABD) in adolescents undergoing major orthopaedic
      surgery. METHODS: Twenty adolescents were studied prospectively; 10 patients in
      group A donated 20% of the circulating blood volume on 2 occasions, whereas 10
      patients in group B donated 10% on 4 occasions. RESULTS: The amount of blood
      donated, subjective tolerance, cardiovascular changes during the procedure and
      pre-operative haemoglobin level did not differ between the study groups (group A
      111+/-16 vs. group B 106+/-10 g/l). The increase in erythropoietin was greater
      and occurred sooner in group A than in group B. CONCLUSION: In adolescents ABD is
      feasible with a reduced number of appointments as they demonstrate tolerance to
      phlebotomies with a volume which is double the standard per deposit.

PMID- 10895097
TI  - Evaluation of leukocyte-depleted platelet concentrates obtained by in-line
      filtration.
AB  - BACKGROUND AND OBJECTIVES: The use of leukocyte-depleted platelet concentrates
      (PCs) is justified, yet questions remain regarding their properties. We have
      assessed the in vitro quality of WBC-reduced PCs obtained by using a new in-line
      filter. MATERIALS AND METHODS: Twenty blood units were randomized for standard
      component preparation, or for processing including in-line leukodepletion of
      platelet-rich plasma using an ATS(TM) PL Pall filter. The resultant PCs were
      compared during storage for several in vitro platelet quality parameters, content
      of cytokines and anaphylatoxins, and coagulation markers. RESULTS: In-line
      filtration of platelet-rich plasma through ATS PL was highly efficient rendering
      PCs with 99.93% less white blood cells (WBCs) than standard PCs. During storage
      for up to 9 days, leukocyte-depleted units displayed platelet content,
      biochemical parameters, and platelet surface expression of glycoproteins Ibalpha,
      IIb/IIa, CD62 and CD63, similar to those of standard units. However, in-line
      leukocyte-reduced PCs displayed no significant accumulation of IL-6 and IL-8
      during storage in contrast to standard units. Moreover, while storage promoted
      complement activation with C3a and C4a liberation in both WBC-reduced PCs and
      standard units, the concentration of these anaphylatoxins after the 9-day storage
      period was higher in the former group. Finally, all units, standard and leukocyte
      reduced, displayed a similar storage-promoted rise in TGF-beta(1), and a mild
      prolongation of activated partial thromboplastin and prothrombin times.
      CONCLUSION: In-line filtration during component preparation appears as an easy
      and effective procedure for obtaining prestorage leukocyte-depleted PCs. During
      subsequent blood bank storage, these WBC-reduced PCs display, in comparison with
      standard PCs, normal in vitro platelet properties, decreased accumulation of
      cytokines IL-6 and IL-8, and increased complement activation.

PMID- 10895098
TI  - Collection efficiencies of CD34+ progenitor cells and mononuclear cells in
      leukapheresis products quantified by flow cytometry and calculated on the basis
      of a new formula.
AB  - BACKGROUND AND OBJECTIVES: Optimal mobilization and harvest of hematopoietic
      progenitors are essential for peripheral blood stem cell transplantation after
      myeloablative high-dose chemotherapy. Conflicting data have been published
      concerning the most useful, cost-effective collection strategy which is also
      convenient for patients. MATERIALS AND METHODS: A total of 66 leukaphereses in 20
      patients were retrospectively evaluated. We assessed the predictive value of the
      number of white blood cells, mononuclear cells (MNCs) and CD34+ cells in
      peripheral blood for the yield of CD34+ cells in leukapheresis products. The
      concentrations of MNCs and CD34+ cells were quantified simultaneously by a flow
      cytometric procedure using fluorescent microparticles. Their collection
      efficiencies were calculated based on a newly developed formula. RESULTS: The
      collected hematopoietic progenitor concentration could be predicted only by the
      number of peripheral blood CD34+ cells prior to apheresis (r = 0.902; p<0.01).
      Furthermore, the mobilization of at least 30 CD34+ cells/microl peripheral blood
      was a good predictor that a single leukapheresis would yield a minimum of
      2.0x10(6) CD34+ cells/kg body weight. The collection efficiencies calculated by
      the new formula were 55.2+/-10.7% and 57.7+/-11.2% for MNCs and CD34+ cells,
      respectively. CONCLUSION: The precise quantification of MNCs and CD34+ cells by a
      direct flow cytometric assay, as well as the new formula to determine the
      collection efficiencies, has an impact on optimizing high-quality stem cell
      products.

PMID- 10895099
TI  - An extended lymphocytotoxicity test for patients treated with lymphocytotoxic
      antibodies.
AB  - BACKGROUND AND OBJECTIVES: After organ transplantation, HLA antibodies (HLA-Ab)
      stimulated by transplant or transfusion are usually indistinguishable from
      passive therapeutic lymphocytotoxic antibodies (LyAb), e.g. antilymphocyte
      globulin (ALG), antithymocyte globulin (ATG) and OKT3, by standard
      lymphocytotoxicity tests (LCTs). Herein, an extended technique capable of
      distinguishing between these two types of antibodies is described. MATERIALS AND
      METHODS: Serum samples from 11 patients who received therapeutic antibodies were
      screened for HLA-Ab by LCTs. The administered LyAb were murine OKT3 (n = 2),
      equine ALG (n = 3), rabbit ATG (n = 2), and combinations of ALG and OKT3 (n = 1),
      ATG and ALG (n = 1), and ATG and OKT3 (n = 2). To discriminate between
      therapeutically applied antibodies and active HLA alloimmunization, the sera were
      preincubated with species-specific anti-Fc IgG, thus blocking the therapeutic
      antibodies. RESULTS: The sera of all patients treated showed strong positive
      lymphocytotoxic reactions [panel reactive antibodies (PRA) 50-100%]. After
      incubation with the corresponding Fc antibodies, in 9 of the 11 samples the
      amount of PRA decreased to the level present before transplantation (0-18%). In
      the remaining cases, new-onset alloimmunization was detected. CONCLUSION: This
      extended LCT allows the screening of serum samples for active HLA-Ab even in the
      presence of therapeutic LyAb.

PMID- 10895100
TI  - Detection of TT virus infection in HCV-infected blood donors from southwestern
      china.

PMID- 10895101
TI  - Hepatitis C virus prevalence among blood donors from South India.

PMID- 10895102
TI  - Genotype analysis of hepatitis C virus in Brazilian hemophiliacs and blood
      donors.

PMID- 10895103
TI  - Methods, who cares?

PMID- 10895104
TI  - Strategies to evaluate metabolic stress and catabolism by means of immunological
      variables.
AB  - In this article, we outline how metabolic stress and catabolism are set off and
      influenced by the neuroendocrine network that interacts intensely with the immune
      system. When evaluating metabolic stress in individuals, the vast ocean of
      mediators, cell-surface markers and intracellular components that participate in
      metabolism and catabolic or anabolic changes make it necessary to focus on
      specific entities that may best mirror all these events. T cell responsiveness
      and factors that orchestrate the T helper type 1 and type 2 balance form an
      immunological mirror that can competently reflect catabolism and metabolic
      stress.

PMID- 10895105
TI  - Tracer methodology in whole body and organ balance metabolic studies: plasma
      sampling is required. A study in post-absorptive rats using isotopically labeled
      arginine, phenylalanine, valine and leucine.
AB  - BACKGROUND AND AIMS: Radioactive and stable amino acid isotopes are frequently
      used in metabolic research. Blood cells contain amino acid transporters, which
      may influence tracer distribution in blood. The aim of this study was to
      determine whether plasma or whole blood specific activity or enrichment of amino
      acid tracers should be used in the calculation of whole body and organ production
      rates. METHODS: Seven male Wistar rats were infused with L-[2,3-(3)H]-Arginine, L
      [2, 6-(3)H]-Phenylalanine, L-[3,4-(3)H]-Valine, and [L-[4,5-(3)H]-Leucine. Whole
      body and portal drained visceral, hepatic and renal production rates of arginine,
      phenylalanine, valine and leucine were determined in plasma and in whole blood.
      RESULTS: Amino acid tracers that equilibrate well between plasma and blood cells
      (for instance phenylalanine, valine and leucine) yield similar whole body
      production rates when whole blood or plasma is sampled. Also, organ production
      rates measured using these amino acid tracers are consistent. However, a
      discrepancy exists between the whole body production rate and the sum of PDV,
      hepatic and renal production rates. When tracers are used that do not equilibrate
      well between plasma and blood cells (for instance arginine) the use of whole
      blood specific activity in the calculations yield overestimations of whole body
      and organ production rates. CONCLUSION: From our data we recommend plasma
      sampling and strongly advise against whole blood sampling in metabolic organ
      balance studies in which amino acid tracers are used.

PMID- 10895106
TI  - Fish intake and blood lipids in fish eating vs non-fish eating communities of
      coastal south India.
AB  - The lower blood lipid levels and lower incidence of coronary heart disease in
      fish eating populations has been attributed to the unusual n-3 fatty acids
      present in their fish diet. In order to test this hypothesis, a cross-sectional
      study was proposed to evaluate the lipid profile in free-living men and women of
      fish eating and non-fish eating populations aged between 20 to 70 years in
      coastal villages of the district of Nellore, in south India. The mean
      concentrations of total serum cholesterol and triacylglycerols were found to be
      lower in fish eating than in non-fish eating populations. Significant differences
      were observed between populations for certain age groups. The serum phospholipid
      content was lower in fish-eating than non-fish eating populations and the
      difference was found to be significant only for women. The mean total cholesterol
      and triacylglycerol levels were found elevated consistently as the age advanced
      in both sexes and populations. There were significant differences for blood
      lipids between men and women in some age groups. The percentile cut-off values
      for cholesterol and triacylglycerol were lower in fish eating as compared to non
      fish eating group. Prevalence of hypercholesterolemia and hypertriglyceridemia (>
      or = 200 mg/dl) was significantly lower in fish eating people indicating less
      proneness to cardiovascular risk. The data indicate that eating of fish may have
      a role in ameliorating the risk of coronary heart disease.

PMID- 10895107
TI  - Compliance of orthopaedic patients with postoperative oral nutritional
      supplementation.
AB  - BACKGROUND: Studies have shown clinical benefits of nutritional supplementation
      in orthopaedic and elderly patients in both under and well nourished groups.
      However, patient compliance with the supplementation has not been reported. AIM:
      To assess level of patient compliance with nutritional supplementation when
      prescribed postoperatively to unselected orthopaedic patients as part of a large
      controlled trial researching the clinical benefits of non-targeted nutritional
      supplementation. METHODS: Patients in the intervention group were prescribed two
      oral supplements each day of their hospital stay, in addition to usual meals.
      Information describing the supplements was given by the dietitian. Supplements
      were issued on drug rounds and the proportion of each drink consumed was recorded
      and collated. Patients could choose to change the type of drink or to discontinue
      the supplements completely at any time. Twenty-four hour food intake was analysed
      for a random sub-sample of 48 patients. RESULTS: Eighty-four patients (27 men, 57
      women; mean age, 72 years) were prescribed supplements. Median length of stay was
      14.4 days. Supplements were taken for a mean of 6.7 days. Median compliance was
      14.9%. Despite this, median energy intake in the study group was 1523 kcal/day
      and 1289 kcal/day in the control (P= 0. 0214). CONCLUSION: Compliance with non
      targeted, postoperative nutritional supplementation is poor in unselected
      orthopaedic patients but even low levels of supplementation significantly
      increase energy intake.

PMID- 10895108
TI  - Antioxidant status of surgical patients receiving TPN with an omega-3-fatty acid
      containing lipid emulsion supplemented with alpha-tocopherol.
AB  - BACKGROUND: LCT lipid emulsions and even more fish oil-containing lipid emulsions
      are under debate regarding their tocopherol and PUFA content as well as their
      effect on the antioxidative status especially in patients with oxidative stress.
      METHODS: Thirty-three patients undergoing major abdominal surgery were randomly
      assigned to receive either an alpha-tocopherol-supplemented (562 micromol/l)
      MCT/LCT/omega-3-acid triglycerides (MLF, 5/4/1 w/w/w, 20%) emulsion or a soybean
      oil-based LCT emulsion (20%). The TPN regimen continuously provided 1.4 g fat kg
      bw(-1)d(-1)over 5 days. RESULTS: Plasma antioxidant concentrations were strongly
      reduced by surgical treatment. Following 5 days of TPN with the MLF emulsion,
      mean plasma alpha-tocopherol increased by 20.0 micromol/l (1.98 micromol/mmol
      lipid), while nearly no change was observed in the LCT emulsion group. In both
      groups, plasma concentrations of all non-supplemented antioxidants (vitamin C,
      carotenoids, selenium) as well as serum total antioxidant capacity further
      decreased during TPN. The concentrations of plasma cholesterol oxidation products
      as a measure of in vivo lipid peroxidation revealed no changes over the TPN
      period in either group. CONCLUSION: In contrast to the LCT emulsion,
      administration of the a-tocopherol supplemented MLF lipid emulsion normalized a
      tocopherol plasma concentrations. Despite its high long-chain PUFA content, no
      hint for increased lipid peroxidation was found.

PMID- 10895109
TI  - Total body water and percentage fat mass measurements using bioelectrical
      impedance analysis and anthropometry in spinal cord-injured patients.
AB  - BACKGROUND AND AIMS: Spinal cord injured patients may be adversely affected by
      disturbances of nutritional status, particularly malnutrition and fat mass
      overload. Malnutrition increases the risk for development of pressure sores, and
      fat mass excess increases the cardiovascular and respiratory risks of these
      patients, as well as predisposing to the development of diabetes mellitus,
      pressures sores and bony fractures. Body impedance analysis and anthopometry are
      easy bedside methods for body composition assessment. The aims of the study were
      to validate, in 20 spinal cord injured patients, body impedance analysis as a
      means to estimate total body water, and to validate a skinfold measurement of
      percentage fat independent of hydration of fat-free mass in the same population.
      METHODS: Total body water was measured by (18)O dilution as a reference method.
      Impedance and anthropometric measurements (four different skinfolds) were
      obtained. The results of total body water given by impedance analysis and
      calculated with three formulas were compared to the reference method. The fat
      mass percentage obtained with each of the skinfolds using the 3-compartment
      Siri's formula was compared to a reference value using the sum of the skinfolds.
      RESULTS AND CONCLUSION: The formula using 100 kHz resistance, height, weight and
      gender overestimated total body water by only 0.76 +/- 1.85 L, with an acceptable
      concordance with labeled water results. The formula with 50 kHz resistance was
      less accurate and concordant. Each skinfold may be used for assessing percentage
      fat mass. Based on these findings, we feel that the triceps skinfold, whose the
      variability is the lowest compared to the reference values, can be used alone in
      clinical practice.

PMID- 10895110
TI  - Prevalence of malnutrition on admission to four hospitals in England. The
      Malnutrition Prevalence Group.
AB  - AIMS: The primary objective was to estimate prevalence of malnutrition on
      admission to four hospitals. Secondary objectives included assessing the
      relationship between nutritional status and length of hospital stay, numbers of
      new prescriptions, new infections and disease severity. METHODS: We entered
      eligible patients according to predefined quotas for elective and emergency
      admissions to 23 specialties. We measured height, weight, Body Mass Index and
      anthropometrics, and recorded history of unintentional weight loss. Patients who
      had lost > or = 10% of their body weight, had a Body Mass Index <20, or had a
      Body Mass Index <20 with one anthropometric measurement <15th centile were
      considered malnourished. RESULTS: Of 1611 eligible patients, 761 did not
      participate; 269 were too ill; 256 could not be weighed; and 236 refused consent.
      Eight hundred and fifty were subsequently evaluated. Prevalence of malnutrition
      on admission was 20%. Length of stay, new prescriptions and infections and
      disease severity were significantly higher in the malnourished. CONCLUSIONS: One
      patient in every five admitted to hospital is malnourished. Although this figure
      is unacceptably high, it may underestimate true prevalence. Malnutrition was
      associated with increased length of stay, new prescriptions and infections.
      Malnutrition may also have contributed to disease severity.

PMID- 10895111
TI  - Expert Working Group report on nutrition in adult patients with renal
      insufficiency (part 1 of 2).

PMID- 10895112
TI  - Timely nutrition screen for hospital patients.

PMID- 10895114
TI  - Partnerships: the way forward.

PMID- 10895115
TI  - Quality assurance for nursing and midwifery education: an analysis of the
      approach in England.
AB  - The main purpose of this paper is to discuss conceptual and policy developments
      for external quality assurance for nurse and midwifery education in England. The
      current framework was implemented in the academic year 1998/99, and is the
      subject of a three year evaluation commissioned by the English National Board for
      Nursing, Midwifery & Health Visiting (ENB). The methods which are being used to
      evaluate the quality assurance arrangements will be discussed within the context
      of nursing and midwifery education and practice. The ultimate aim of
      professionally accredited nursing and midwifery education is to ensure the
      development of practitioners who are fit for purpose, practice and award. It
      follows that the quality assurance processes should have the capacity to
      demonstrate the extent to which professional education meets this aim. This paper
      will discuss this issue, with particular emphasis on the collaborative review
      process which is being undertaken by the Quality Assurance Agency and the
      statutory body for nursing, midwifery and health visiting education. The paper
      concludes with a discussion of the changes proposed by the government for nursing
      and midwifery education, and considers the potential impact for quality assurance
      of health care education.

PMID- 10895116
TI  - Fit for practice: Project 2000 student nurses' views on how well the curriculum
      prepares them for clinical practice.
AB  - This paper presents the findings from a small study, which compared student
      nurses' views on how well they felt the Project 2000 curriculum had prepared them
      for their first clinical placements. The views of two student nurse cohorts were
      obtained using a questionnaire developed for the purpose. The curriculum for the
      'old' cohort allowed very little clinical time during the first 18 months and
      focused on academic classroom-based learning. The curriculum was subsequently
      restructured so that students on the 'new' curriculum experienced greater
      emphasis on practice and theory to practice links, and undertook their first
      clinical placement much earlier on in their course. Although statistical analysis
      of difference between the two cohorts suggests that students from the 'new'
      cohort felt they were better prepared, the actual differences in scores was
      small. The findings of this study provide only modest evidence of improvement in
      'new' student nurses' views of how well they felt they had been prepared for
      their first placement.

PMID- 10895117
TI  - Redressing the power and effect of significance. A new approach to an old
      problem: teaching statistics to nursing students.
AB  - Many barriers to learning are present when teaching research methods. Developing,
      within students of nursing, the skills of reading and interpreting research
      reports is vital if the profession is to contribute to the general aim of
      achieving a sound basis for all health care interventions. This paper overviews
      the current move toward evidence based practice, the challenges that are present
      when teaching research to nursing students and offers an approach to teaching
      quantitative research that will help students of nursing to understand the key
      concepts that form the basis of inferential statistics. In this work we argue
      that the traditional emphasis on probability and statistical significance needs
      to be redressed and that effect size and power should form the basis of teaching
      students the concepts involved in inferential statistics. We argue that
      introducing students to the key concepts in statistical decision making in a
      particular order, effect size then power and lastly statistical significance,
      will lead to a better understanding of Type I and Type II errors. After all, the
      purpose of hypothesis testing is to detect a treatment or intervention effect.
      Power is dependent upon the size of the treatment effect, thus it must be
      introduced after effect size. Students, we argue, must be able to understand the
      concept of effect size. We consider this to be a foundational concept that will
      help to develop a firmer grasp of the decision making processes involved in
      hypothesis testing. Such an approach will form a more logical approach to
      teaching this subject and will allow for the use of real world examples to form
      the basis of learning.

PMID- 10895118
TI  - Achieving change through reflective practice: closing the loop.
AB  - This paper draws on a small scale, exploratory study which was conducted in the
      clinical area in the early 1990s (Page 1992). The study drew on the principles of
      reflective practice in order to enable practitioners to identify learning needs
      in relation to cardiopulmonary resuscitation (CPR) procedures. Whilst
      considerable benefit from the reflective sessions was noted, one unanticipated
      and unpalatable outcome was what might be termed professional apathy. This was
      manifest in several ways, most importantly in that issues 'for action',
      identified through reflection, were not prioritised or acted upon. Whilst partial
      responsibility for this may lie with the somewhat naive way in which the
      reflective process was facilitated, some responsibility also rests with the
      nurses in question. One possible explanation is that, for changes in practice to
      occur, the planning and management of change should form an integral part of the
      reflective cycle. This point has been largely absent in the reflection literature
      to date. Such concerns are reviewed here in the context of nurse education's
      ongoing involvement with the notion of reflective practice and the role of the
      educationalist in the clinical area. The current political backdrop of 'quality
      initiatives' to create and demonstrate high standards of clinical care may be
      useful in advancing the debate.

PMID- 10895119
TI  - Training and education: an analysis of quality assurance in teaching and nursing
      education.
AB  - There is a continuing tension between training and education in vocational higher
      education courses. The debate in nursing has been heightened by the transfer of
      courses into higher education and staffing problems in the NHS. Comparisons with
      other occupations can help prevent introspection in analysis of policy issues in
      nursing. Teacher training is a particularly useful comparator because it entered
      higher education before nursing, and teachers have failed to maintain a level of
      autonomy that nurses would once have envied. This paper compares nursing and
      teacher training with particular reference to quality assurance. The UK
      government has adopted a centralized quality assurance and funding system for
      teacher training. Nursing is included in higher education quality assurance
      systems but funding is devolved. The tensions between training and education
      within nursing and teacher training are examined, and implications for the
      development of nursing considered.

PMID- 10895120
TI  - Untangling the Web... barriers and benefits for nurse education... an Australian
      perspective.
AB  - The Internet... a Web of information technology. The potential exists now and
      increasingly in the future to use this technology to deliver widely distributed,
      creative, innovative learning to students across vast distances and at times
      which suit individual needs. The implications of this technology for nurse
      education, and indeed health care in general, are exciting. The technology is
      growing at such a vast rate that it would be easy to blindly accept it and
      promote its use. However, there is a need to stop and consider some of the
      practical barriers to the use of this technology, particularly for nursing
      education.

PMID- 10895121
TI  - Future directions for gerontology: a nursing perspective.
AB  - This paper discusses the contribution nursing has made to the development of
      person-centred services, and the influence of gerontology upon such developments.
      It examines traditional attitudes to medicine and nursing, when curing was all
      important and caring treated as secondary and the shift away from this attitude
      to a more holistic approach to nursing, where the dignity of the patient is an
      important issue. It argues that good practice utilizes different sources of
      knowledge, including intuitive knowledge, and discusses the integrated programme
      of policy, development, research and education activities that the Royal College
      of Nursing is developing. The options currently available to anyone wishing to
      study gerontology are discussed, and the pros and cons of the current emphasis on
      broad-based clinical and educational experience prior to specialization analysed.
      The key aim of the RCN is to develop the specialism of gerontological nursing and
      the quality of care experienced by older people. With this end in view, this
      paper describes the education programme being developed by the RCN, leading to
      the award of Gerontological Nurse Specialist--a person able to demonstrate
      knowledge of rehabilitation, clinical assessment, health care assessment and a
      holistic knowledge of the ageing process.

PMID- 10895122
TI  - The place of nursing history in an undergraduate curriculum.
AB  - It has been stated that the history of nursing is, in itself, a suitable subject
      for research (Maggs 1996) but that historians of nursing have looked to the
      broader social sciences for their frame of reference. Over the past decade or
      more there has been debate as to the purposes of nursing history and its
      relevance to the education of modern nurses and to practice. There is also
      discussion as to the contribution nursing history has, or could, make to nursing
      theory and its development. Nursing history has been part of nursing curricula
      for many years in some shape or form, with variation in its timing, structure,
      content and the emphasis and importance placed on it by nurse educators. We have
      recently reintroduced nursing history to the curriculum in the form of a stand
      alone course. The aim of this paper is to describe the formal reintroduction of
      nursing history into the curriculum and its place in a newly developed honours
      undergraduate programme. A review of the literature will be undertaken which will
      outline the main areas of importance. The review will be followed by a discussion
      of the history of nursing course and its inception. Using points identified in
      the literature, the rationale for content and structure are made and the
      integration of history with theoretical and practical aspects of nursing is
      explained. The impact of the supporting sciences, both physical and behavioural,
      and issues surrounding students efforts to reconcile the art and science of
      nursing are analysed. The introduction has posed questions which are currently
      being addressed and changes will be made for the new academic year.This supports
      the philosophy of the Nursing & Midwifery School that history has relevance to
      the education of nurses and therefore a significant place in the curriculum.

PMID- 10895123
TI  - The role of the personal tutor in the academic context.
AB  - This paper is the second of a series on the role of the nurse teacher and is
      based on a review of the literature and the personal experience of the authors.
      Identifying the most appropriate way to support students in both the academic and
      clinical setting has been a major concern for nurse teachers. The move of nurse
      education into the higher education arena has increased the diverse nature of the
      nurse teachers role and raised questions about the nature and function of the
      personal tutor in relation to students undertaking nursing courses. This paper
      discusses the concept of the personal tutor, with particular focus on the
      academic aspects of the role. The time implication of adopting an all
      encompassing personal tutor role, within the current climate of higher education,
      is considered. The paper also highlights that the roles tutors adopt in practice
      are diverse and usually as a result of convenience rather than identified
      outcomes.

PMID- 10895124
TI  - Did Project 2000 nurse training change recruitment patterns or career
      expectations?
AB  - In the UK, Project 2000 nurse education, introduced over the last eight years,
      aimed to increase the professional status of nurses and enhance skills, focusing
      on wider community care. This paper reports some of the results from a research
      project conducted between 1994 and 1996, funded by the Department of Health
      (Project 2000 Fitness for Purpose 1996). It was hypothesized that the changes in
      Project 2000 training might attract those more academically qualified and lead to
      more rapid career progression. The results found in this study did not support
      either of these hypotheses and suggestions are made about the reasons for the
      negative findings.

PMID- 10895125
TI  - Bladder cancer: one enemy, many fronts.

PMID- 10895126
TI  - Molecular mechanisms and pathways in bladder cancer development and progression.
AB  - BACKGROUND: The basis for bladder cancer development and progression is complex
      and involves genetic abnormalities. These abnormalities yield phenotypic changes
      that allow normal transitional cells to become cancerous and finally acquire the
      "malignant phenotype." METHODS: The authors review the most common genetic
      alterations in bladder cancer and the molecular mechanisms and pathways involved
      in the conversion of normal transitional cell into malignant transitional cancer
      cells. RESULTS: There are several potential genetic changes of the urothelium
      that eventually cause bladder cancer initiation and tumor progression. Some of
      these alterations are also found in other malignancies suggesting that key common
      pathways exist in the development of cancer. CONCLUSIONS: As the roles of certain
      genes or proteins are further elucidated, a better understanding of cancer
      development can aid in the prevention, diagnosis, and treatment of bladder
      cancer.

PMID- 10895127
TI  - Contemporary management of superficial bladder cancer.
AB  - BACKGROUND: Bladder cancer is the second most common urologic malignancy after
      prostate cancer. Superficial bladder cancer presents as a heterogeneous group of
      tumors with variable biological potential. A significant percentage of patients
      diagnosed with superficial cancer will have multiple recurrences, and some will
      progress to invasive disease. METHODS: Patients are stratified into low- or high
      risk for recurrence and progression. We review the most recent literature
      regarding intravesical therapy for superficial bladder cancer, and we summarize
      indications for the use of intravesical agents as well as their efficacy,
      toxicity, and cost. RESULTS: Several intravesical agents are available for the
      treatment of superficial bladder cancer. Patients may be identified as low- or
      high-risk for recurrence and progression. High-risk patients benefit from
      intravesical therapy. CONCLUSIONS: Superficial bladder cancer is a heterogeneous
      group of diseases. Treatment is effective in preventing recurrences and
      progression in the high-risk group.

PMID- 10895128
TI  - Bladder-sparing treatment of invasive bladder cancer.
AB  - BACKGROUND: Radical cystectomy with pelvic lymph node dissection is the standard
      treatment for patients with invasive bladder cancer. However, many alternative
      techniques to spare the bladder have been investigated. METHODS: We review the
      experience reported in the literature on bladder-sparing techniques, including
      transurethral resection, chemotherapy, and radiation for muscle-invasive disease.
      RESULTS: Most comparative studies indicate that local recurrence and survival
      outcomes for bladder-sparing approaches are inferior to those from radical
      cystectomy to control muscle-invasive bladder cancer. CONCLUSIONS: Although
      molecular biologic techniques may have the capacity to identify a subgroup who
      may benefit from a bladder-sparing approach, cystectomy is normally required for
      optimal results.

PMID- 10895129
TI  - Progress in the management of metastatic bladder cancer.
AB  - BACKGROUND: Inadequate survival results from single agents in the management of
      advanced bladder cancer have prompted several trials involving multidrug
      combinations to increase response rates and survival. METHODS: Since the
      development of the MVAC regimen (methotrexate, vinblastine, doxorubicin, and
      cisplatin) and the CMV regimen (cisplatin, methotrexate, and vinblastine), other
      regimens have been tested. We evaluate results from regimens that include
      cisplatin combined with gemcitabine, paclitaxel, or docetaxel, and paclitaxel
      combined with gemcitabine or carboplatin. RESULTS: Objective results observed
      with various new combinations are promising. Objective response (OR) rates of
      41%, 59%, and 71% are reported with a regimen of gemcitabine plus cisplatin.
      Paclitaxel plus cisplatin produced OR rates of 65% and 72%. CONCLUSIONS: The use
      of combination cytotoxic chemotherapy regimens in treating patients with
      metastatic bladder cancer has nearly doubled median survival to 12 months, with a
      3-year survival of approximately 20% to 25%. Caution must be exercised in using
      some of the newer regimens as survival may be inferior compared with the MVAC
      regimen.

PMID- 10895130
TI  - Imaging in oncology. A sonographically well-delineated mass in the kidney.

PMID- 10895131
TI  - Evidence-based medicine and practice guidelines: an overview.

PMID- 10895132
TI  - Evidence-based management of cancer in the elderly.

PMID- 10895133
TI  - Tumors of the thyroid gland: histologic and cytologic features--part 2.

PMID- 10895134
TI  - Reproduction technology in hong kong

PMID- 10895135
TI  - Deletions within the azoospermia factor subregions of the Y chromosome in Hong
      Kong Chinese men with severe male-factor infertility: controlled clinical study.
AB  - OBJECTIVE: To determine the patterns and the prevalence of microdeletions in the
      azoospermia factor subregions of the Y chromosome in Hong Kong Chinese men with
      severe male-factor infertility. DESIGN: Controlled clinical study. SETTING:
      Reproductive centre of a university teaching hospital, Hong Kong. PARTICIPANTS:
      Fifty-eight men with severe male-factor infertility who participated in the in
      vitro fertilisation programme from May 1998 through March 1999, and 46 male
      volunteers with proven fertility. MAIN OUTCOME MEASURES: Polymerase chain
      reaction analysis of DNA from peripheral blood lymphocytes using six loci
      spanning the AZFa, AZFb, and AZFc subregions of the Y chromosome. RESULTS. No
      microdeletions were detected in the fertile controls or in patients with
      obstructive azoospermia. Deletions within the AZFc subregion were found in 9%
      (4/44) of men with non-obstructive azoospermia or severe oligospermia. Neither
      AZFa nor AZFb deletions were detected in any participants. CONCLUSION: Deletions
      within the azoospermia factor subregions of the Y chromosome are associated with
      severe male-factor infertility in Hong Kong Chinese men.

PMID- 10895136
TI  - The effect of ageing on female fertility in an assisted reproduction programme in
      Hong Kong: retrospective study.
AB  - OBJECTIVE: To analyse the effect of ageing on female fertility in an in vitro
      fertilisation programme in Hong Kong. DESIGN: Retrospective study. SETTING:
      University teaching hospital, Hong Kong. PATIENTS: Seven hundred and seventy-one
      women in whom 1336 cycles of in vitro fertilisation were initiated between 1
      January 1986 and 31 December 1995. MAIN OUTCOME MEASURES: Patient age and
      indications for treatment; hormonal response; and the number of cancelled cycles,
      oocytes retrieved, oocytes fertilised, cleaving embryos, embryos transferred, and
      clinical pregnancies. RESULTS: Compared with women aged <or =30 years (n=193),
      women aged > or =36 years (n=398) had a significantly higher cycle cancellation
      rate (19.3% versus 10.4%), fewer oocytes retrieved per retrieval cycle (6.6
      versus 9.0), fewer oocytes fertilised per retrieval cycle (5.0 versus 7.0), fewer
      cleaving embryos per retrieval cycle (4.8 versus 6.8), and lower serum oestradiol
      level (9735 [standard deviation, 5681] pmol/L versus 10 708 [5916] pmol/L)
      despite a larger amount of human menopausal gonadotrophin having been used (all
      variables, P<0.01; Chi squared test). The clinical pregnancy rate per initiated
      cycle (range, 7.5%-13.0%) decreased with advancing age (P<0.01; Chi squared
      test). CONCLUSION: Ageing has a significant deleterious effect on women's
      reproductive capability. Women should be encouraged to seek early medical advice
      and treatment for subfertility.

PMID- 10895137
TI  - The C282Y mutation of the HFE gene is not found in Chinese haemochromatotic
      patients: multicentre retrospective study.
AB  - OBJECTIVE: To detect two novel mutations (C282Y and H63D) of the HFE gene in
      Chinese patients with hepatic iron overload. DESIGN: Multicentre retrospective
      study. SETTING: Four public hospitals, Hong Kong. PARTICIPANTS: Fifty Chinese
      patients who presented from January 1987 through December 1999 with hepatic iron
      overload from various causes. MAIN OUTCOME MEASURES: The DNA from liver biopsy
      samples was tested for HFE mutations by restriction fragment length polymorphism
      analysis. RESULTS: The sample DNA quality was unsatisfactory for analysis of the
      C282Y mutation in one case and the H63D mutation in nine cases. The C282Y
      mutation was not detected in any of the 49 satisfactory samples. Three of the 41
      samples were heterozygous for the H63D mutation and only one was homozygous,
      giving an allele frequency of 6.1%. Of the three H63D-heterozygotes, one had beta
      thalassaemia major, one had beta-thalassaemia minor, and one had hereditary
      spherocytosis. None of the 12 patients who were presumed to have primary
      haemochromatosis were positive for either mutation. CONCLUSIONS: The classical
      form of human leukocyte antigen-linked hereditary haemochromatosis appears to be
      absent form this locality. The H63D mutation is found in a minority (9.8%) of the
      patients, in whom it may act synergistically with an erythropoietic factor.

PMID- 10895138
TI  - Epidemiology of heart failure in Hong Kong, 1997.
AB  - OBJECTIVE: To analyse the epidemiology of heart failure in Hong Kong, 1997.
      DESIGN: Retrospective study with 1-year follow-up. SETTING: Accident and
      emergency departments of 11 hospitals of the Hospital Authority, Hong Kong.
      PATIENTS: All patients admitted to hospital in 1997 with heart failure as the
      primary diagnosis, as shown in their discharge summaries. MAIN OUTCOME MEASURES:
      Demographic data, incidence and prevalence of heart failure, and survival status
      up to 1 year. RESULTS: There were 4589 new and 1614 old cases of heart failure
      that required hospital admission in 1997. The largest age-group was the 75- to 84
      year group; 85% of the patients were older than 65 years and 56% of the patients
      were female. The incidence of heart disease increased with age, approximately
      doubling with each decade of age and reaching an annual incidence of 14 per 1000
      men and 20 per 1000 women older than 85 years. The 1-year mortality rate also
      increased with age, reaching 40% for patients older than 85 years (overall, 32%).
      CONCLUSION: Heart failure is a common problem and has high mortality, especially
      in elderly patients. Detailed analyses of the aetiology and early preventive
      measures are needed to alleviate the problem.

PMID- 10895139
TI  - Laboratory aspects of assisted reproduction.
AB  - A number of advances have been made concerning the laboratory aspects of assisted
      reproduction. Intracytoplasmic sperm injection has revolutionised the treatment
      of male infertility. With the development of better embryo culture media,
      blastocyst transfer is now possible and is likely to reduce high-order multiple
      pregnancy in assisted reproduction treatment. Pre-implantation genetic diagnosis
      has become an alternative to prenatal diagnosis. The recent use of molecular
      biology techniques to detect small genetic defects in men with severe male-factor
      infertility has provided information for the better counselling of these
      patients. Other techniques that are being developed are likely to have a
      tremendous impact on assisted reproduction treatment. These include in vitro
      maturation, follicle culture, and oocyte/ovarian tissue cryopreservation. The
      current status of the developments in the laboratory aspects of assisted
      reproduction is reviewed in this article.

PMID- 10895140
TI  - Recent advances in clinical aspects of in vitro fertilisation.
AB  - While early success rates using in vitro fertilisation ranged from 10% to 15%,
      improved technology has more than doubled that rate, owing to the availability of
      recombinant follicle-stimulating hormone, improved ovarian stimulation protocols,
      and assisted fertilisation technology. This latter technology has already
      revolutionised the management of male-factor infertility. The future goal is to
      further increase the overall pregnancy rate and to reduce the risk of multiple
      gestation by using pre-implantation genetic diagnosis and blastocyst transfer.

PMID- 10895141
TI  - Patient selection for assisted reproductive technology treatments.
AB  - Assisted reproductive technologies refer to procedures in which the oocyte is
      handled or manipulated in vitro before replacement, either as an oocyte or an
      embryo. Because of rapid advances in this area, infertile couples may seek direct
      referral for assisted reproductive treatments, instead of trying simpler measures
      such as ovulation induction and intrauterine insemination. It is important to
      establish whether these conventional infertility treatments are appropriate, as
      such treatments are generally safer, less stressful, and more affordable. On the
      other hand, subjecting infertile couples to unnecessary delay by offering
      inappropriate treatments-for example, ovulation induction for tubal infertility
      or intrauterine insemination for severe male-factor infertility-would reduce the
      overall chance of success because of the age-related decline in female fecundity.
      The choice of infertility treatments thus depends on a balance of factors: the
      chance of pregnancy without treatment; the chance with simpler and safer, but
      less successful, infertility treatments; or the chance with the more complex and
      costly, but more effective, assisted reproductive treatments. The factors that
      should be taken into consideration include the age of the woman, the duration of
      infertility, the causes of infertility, the availability and cost of alternative
      treatments, and-most importantly-the acceptability.

PMID- 10895142
TI  - Microdeletions on the long arm of the Y chromosome and their association with
      male-factor infertility.
AB  - Significant advances in treatment have enabled previously infertile males to
      achieve fatherhood, when only a few years ago they would have had no chance of
      biological paternity. In contrast to the overall success of assisted
      reproduction, the aetiology of male-factor infertility is poorly understood.
      Recent studies have shown, however, that a significant proportion of men with
      severe infertility have microdeletions of the Y chromosome. Furthermore, reports
      have shown that male infants conceived through assisted reproductive techniques
      have inherited the same Y-chromosome microdeletion as their fathers. It has thus
      become important to screen men who are at risk of Y-chromosome microdeletions, as
      this will determine if counselling is needed prior to starting infertility
      treatment. This review examines the significance and limitations of the current
      understanding of Y-chromosome microdeletions in male infertility.

PMID- 10895143
TI  - A 12-month review of autopsies performed at a university-affiliated teaching
      hospital in Hong Kong.
AB  - OBJECTIVE: To review the autopsies performed at a university-affiliated teaching
      hospital over a 12-month period. DATA SOURCES: Records of autopsies performed at
      a university-affiliated teaching hospital during 1997, and Medline literature
      search (1966-1998). STUDY SELECTION: The key words used in the literature search
      were 'autopsy' and 'audit'. DATA EXTRACTION: Data were extracted and analysed by
      the authors. Any discrepant cases (in which the final diagnoses were either
      unexpected or not made before death) were identified from the hospital records.
      DATA SYNTHESIS: Interest in autopsy results has increased, owing to the greater
      emphasis on medical audit and quality assurance procedures. Of the yearly total
      of 403 autopsies, 332 cases were reviewed; the discrepancies found were
      classified as either major or minor, according to their effect on the clinical
      outcome. The major and minor discrepancy rates were 23% and 9%, respectively. In
      2% of cases, the cause of death was due to complications resulting from surgical
      intervention. These discrepancy rates were comparable to the figures quoted in
      the literature. CONCLUSION: Autopsy is a valid medical quality-assurance
      mechanism in Hong Kong.

PMID- 10895144
TI  - The association between cigarette smoking and ocular diseases.
AB  - OBJECTIVE: To review the effect of smoking on common ocular disorders. DATA
      SOURCES: Medline literature search, 1966 to 1999. STUDY SELECTION: The following
      key words were used: smoking; Graves' disease, age-related macular degeneration;
      glaucoma; cataract. DATA EXTRACTION: Epidemiological and experimental studies
      were reviewed. DATA SYNTHESIS: Cigarette smoking is an important risk factor for
      cardiovascular, respiratory, and malignant diseases. There is also a strong
      association between smoking and a number of common eye diseases, which include
      Graves' ophthalmopathy, age-related macular degeneration, glaucoma, and cataract.
      Despite the multifactorial aetiology of these ocular syndromes, smoking is an
      independent risk factor that has dose-response effects. It causes morphological
      and functional changes to the lens and retina due to its atherosclerotic and
      thrombotic effects on the ocular capillaries. Smoking also enhances the
      generation of free radicals and decreases the levels of antioxidants in the blood
      circulation, aqueous humour, and ocular tissue. Thus, the eyes are more at risk
      of having free-radical and oxidation attacks in smokers. CONCLUSION: Smoking, if
      continued, may perpetuate further ocular damage and lead to permanent blindness.
      Cessation of smoking and avoidance of passive smoking is advised to minimise the
      harmful effects of smoking on the eyes.

PMID- 10895145
TI  - Oral care for children with leukaemia.
AB  - OBJECTIVES: To review the oral care regimens for children with acute leukaemia,
      and to present an easy-to-follow oral care protocol for those affected children.
      DATA SOURCES: Medline and non-Medline search of the literature; local data; and
      personal experience. STUDY SELECTION: Articles containing supportive scientific
      evidence were selected. DATA EXTRACTION: Data were extracted and reviewed
      independently by the authors. DATA SYNTHESIS: Cancer is an uncommon disease in
      children, yet it is second only to accidents as a cause of death for children in
      many countries. Acute leukaemia is the most common type of malignancy encountered
      in children. The disease and its treatment can directly or indirectly affect the
      child's oral health and dental development. Any existing lesions that might have
      normally been dormant can also flare up and become life-threatening once the
      child is immunosuppressed. Proper oral care before, during, and after cancer
      therapy has been found to be effective in preventing and controlling such oral
      complications. CONCLUSION: Proper oral care for children with leukaemia is
      critical. Long-term follow-up of these children is also necessary to monitor
      their dental and orofacial growth.

PMID- 10895146
TI  - Obstructive sleep apnoea syndrome: treatment update.
AB  - Obstructive sleep apnoea syndrome is a common but underrecognised disorder with
      associated substantial morbidity and mortality. Excessive daytime sleepiness
      caused by the disorder leads to poor work performance and increases the risk of
      an individual having an automobile accident. The main objective of treatment for
      sleep apnoea is the relief of disabling daytime sleepiness and the improvement of
      quality of life. Conservative measures such as weight reduction and the avoidance
      of alcohol should be initiated when appropriate. Nasal continuous positive airway
      pressure devices have remained the standard treatment since it was first
      introduced in 1981. Oral appliances provide an alternative treatment choice in
      mild-to-moderate cases, whereas surgery is useful in selected cases.

PMID- 10895147
TI  - An audit of the early outcomes of ambulatory inguinal hernia repair at a surgical
      day-care centre.
AB  - Ambulatory surgery has been recently gaining popularity owing to the increasing
      constraints on public-sector health care resources. Inguinal hernia repair is one
      of the most common day-case operations. This study was conducted to audit the
      early outcomes of 271 consecutive day-case inguinal hernia repairs performed at
      the Day Surgery Centre of the Tung Wah Hospital from 1 December 1995 through 31
      December 1998. No patients died on the day of their surgery; in 265 (97.8%)
      cases, patients were discharged home on the day of their operation. Two patients
      required readmission because of fever and urinary retention, and the
      postoperative morbidity rate was approximately 5% (14/271 cases). Wound
      complication was the most common morbidity encountered and pain was the most
      common discomfort experienced by patients at home. These results suggest that
      ambulatory hernia repair can be performed safely in a day centre and yields
      excellent early outcomes.

PMID- 10895148
TI  - Interferon treatment for multiple sclerosis patients in Hong Kong.
AB  - We report on nine patients with multiple sclerosis who had received interferon
      beta-1a treatment for 6 months or more. Seven patients were Chinese and two were
      Caucasian. Seven patients had the relapsing-remitting type of multiple sclerosis,
      one had the primary-progressive type, and one had the progressive-relapsing type.
      Among the six compliant patients with the relapsing-remitting type of disease,
      four had less frequent relapses after treatment. This study could not show
      whether or not the use of interferon beta-1a was beneficial to non-compliant
      patients, or patients with other types of multiple sclerosis.

PMID- 10895149
TI  - Facial nerve palsy and Kawasaki disease.
AB  - We report on a case of facial nerve palsy associated with Kawasaki disease in a 2
      year-old boy. Facial nerve palsy is one of the rare neurological manifestations
      of Kawasaki disease. Twenty-seven other cases that have been reported in the
      literature are reviewed. There is a high incidence of coronary artery aneurysm
      (52%) and a female predilection in patients with Kawasaki disease. The facial
      palsy associated with the disease is self-limiting. Recovery is spontaneous in
      surviving patients, although the use of intravenous immunoglobulin may be able to
      hasten the recovery.

PMID- 10895150
TI  - Three different presentations of bulimia nervosa.
AB  - This case report describes the different presentations of three women with
      bulimia nervosa, all of whom demonstrated purging behaviour. Two of the patients
      also had hypokalaemia, whereas the third exhibited Russell's sign-that is,
      calluses on the dorsum of each hand. Drug treatment and psychosocial intervention
      improved the condition of all three patients. The report emphasises the need for
      both health care professionals and the public to recognise this potentially
      dangerous but treatable disorder.

PMID- 10895151
TI  - A case of Penicillium marneffei osteomyelitis involving the axial skeleton.
AB  - Fungal infection of bone by Penicillium marneffei is rare. We report on a case of
      Penicillium marneffei infection in a Filipino woman, which involved multiple soft
      tissue abscesses and infection of the axial skeleton. Early diagnosis and
      treatment of this potentially reversible disease is emphasised. Such an approach
      is essential to prevent bony destruction from becoming too advanced and, more
      importantly, to prevent any damage to the spinal cord from occurring.

PMID- 10895152
TI  - Maggots in ulcers: friend or foe?

PMID- 10895153
TI  - Paper version of the Hong Kong Medical Journal should stay.

PMID- 10895154
TI  - Constant clinical surveillance is also important when monitoring blood gases.

PMID- 10895155
TI  - Conceptual changes in cancer chemotherapy--biochemical modulation of 5-FU from
      bench to clinic.
AB  - Recently, a demand for therapy of higher usefulness in cancer patients has
      increased. We described in this paper a therapeutic modality which is based on
      SRC (self-rescuing concept) featuring dual activity, i.e., effect-enhancing
      activity and adverse reaction-reducing activity. We presented the theory and
      practice of S-1, a novel oral fluoropyrimidine anti-cancer agent designed to
      enhance anticancer activity and reduce gastrointestinal toxicity through the
      deliberate combination of the following components: an oral fluoropyrimidine
      agent tegafur; a DPD inhibitor (CDHP) which is more potent than uracil used in
      UFT; and an ORTC inhibitor (Oxo) which localizes in the gastrointestinal tract. S
      1, as a combination drug with a molar ratio of 1:0.4:1 in FT, CDHP, and Oxo,
      respectively. A clinical pharmacology study to examine blood concentrations of 5
      FU after twice-a-day administration of S-1 at a dose 40 mg/m2. Consequently ,
      blood concentrations of 5-FU were 60 to 200 ng/m/ in all twelve patients
      examined. The overall response rate was 44.6% (45/101). In addition, the
      incidence of adverse reactions judged to be G3 or higher was 10% or less.
      Furthermore, we referred to combination therapy with 5-FU (CIV)(5-FU: 250 to 350
      mg/body, 24-hour CVI, consecutive days) and low-dose cisplatin (CDDP: 3 to 5
      mg/body, iv, 5 days/week) in which CDDP was used as modulator of 5-FU. Low-dose
      FP therapy provided response rates as high as 40 to 60% in 163 patients with
      sorts of gastrointestinal cancers except pancreas cancer. The incidence of
      adverse reactions which were judged to be G3 or higher was 2.5% (4/163) in nausea
      and vomiting. The incidences of other adverse reactions were 1% or less. And to
      the theory and practice of combination therapy with 5-FU (CVI) 24-hour CVI; 5-FU:
      750 to 1000 mg/body/day on Monday, Wednesday, and Friday; withdrawal on Tuesday,
      Thursday, Saturday, and Sunday) intermittent administration and low-dose CDDP (3
      to 5 mg/body/day day 1-5/w) consecutive administration in which a difference in
      cell cycle between gastrointestinal mucosal cel l and tumor cell or between bone
      marrow cell and tumor cell was utilized . Little adverse reactions, e.g.,
      diarrhea and stomatitis, were observed despite the overall response rate which
      was as high as 52.4% (22/42). We intend in the future to combine the above
      mentioned therapeutic modalities provoking less adverse reactions and being
      gentle to patients with cancer in an effort to further increase their life
      expectancy.

PMID- 10895156
TI  - Result of 11,946 gastric cancer treatment with immunochemosurgery.
AB  - Although the therapeutic results of gastric cancer have markedly improved, it
      still remains the most common of cancer deaths in Korea. Annually more than 700,
      and all together 11,946, gastric cancer patients were surgically treated from
      1970 to 1998 at Seoul National University Hospital. Stage III gastric cancer is
      already a systemic disease, Radical surgery alone cannot cure the patient, and
      about 35% recurred within 2-3 years. To improve the prognosis of advanced gastric
      cancer, systemic treatment such as immunotherapy and chemotherapy is required in
      the early postoperative period to kill the micrometastatic or remaining cancer
      cells after curative resection. We evaluated the survival rate and prognostic
      factors for 9,262 consecutive patients from 1981 to 1996. The clinicopathologic
      variables used for evaluating prognostic values were classified into patient, 
      tumor- and treatment-related factors. The prognostic significance of treatment
      modality was evaluated in stage III gastric cancer. The five-year survival rates
      were 55.9% for overall patients and 64.8% for patients who received curative
      resection. Radical lymph node dissection was found to produce survival gains in
      patients with stage II and IIIa. For postoperative adjuvant therapy,
      immunochemotherapy was most effective in patients with stage III. In multivariate
      analysis, curability of operation, depth of invasion, and ratio of involved-to
      resected lymph nodes were the significant prognostic factors. Consequently, early
      detection and real curative resection with radical lymph node dissection,
      followed by immunochemotherapy (particularly in patients with stage III gastric
      cancer) should be recommended as a standard treatment principle for patients with
      gastric cancer.

PMID- 10895157
TI  - Role of pHyde novel gene product as an intrinsic factor for apoptotic pathway in
      prostate cancer.
AB  - Induction of apoptotic cell death mechanism can be regulated by internal
      factor(s), such as by gene product(s) that directly upregulate the apoptosis
      pathway or indirectly by down-regulating the anti-apoptosis gene. This
      homeostasis is a normal phenomenon in a biological system disturbed by cancer. It
      is thus important to find any gene functioning as an upregulator for the
      apoptosis pathway that may have a potential application in the context of cancer
      gene therapy. We have cloned a novel rat gene, denoted as pHyde, that fulfilled
      this objective. Internally, this pHyde gene product renders the stable
      transfectant of rat prostatic cancer cell lines more susceptible to apoptosis
      even without any external inducer. By using an external agent, such as 5-fluoro
      2'-deoxyuridine (FdUr), apoptotic responses of the stable transfectants are even
      higher, suggesting that both intrinsic and extrinsic factors work
      synergistically. The pHyde gene product was termed an intrinsic factor, whereas
      FdUr was considered an extrinsic factor for the apoptosis in rat prostate cancer
      model.

PMID- 10895158
TI  - Docetaxel (Taxotere) in the treatment of non-small cell lung cancer (NSCLC)--is
      there a role for a new chemotherapy programme?
AB  - Phase II with single-agent docetaxel, in second-line NSCLC, demonstrated an
      overall response rate of 20%, with a median response duration of 7 months and a
      median survival time of 9 months. These results suggested that docetaxel had
      promising activity in patients with platinum-resistant or refractory NSCLC. Phase
      III studies in this patient population subsequently confirmed this activity;
      docetaxel prolonged survival when compared to either vinorelbine/ifosfamide or
      the best supportive care. The phase II studies with docetaxel in first-line NSCLC
      produced an overall response rate of 30% in evaluable patients, with a median
      response duration of 6 months and a median survival time of 9 months. A phase III
      randomized study demonstrated a significant improvement in survival and time to
      progression with docetaxel, compared to the best supportive care. Based on the
      activity observed with single-agent docetaxel, combination and multimodality
      studies with docetaxel have also been conducted. Docetaxel is an active agent in
      first- and second-line NSCLC. Ongoing studies in the front-line treatment of
      NSCLC will further define the role of docetaxel in the neo-adjuvant setting.

PMID- 10895159
TI  - New advances in the treatment of locally advanced non-small cell lung cancer and
      breast cancer.

PMID- 10895160
TI  - Chemotherapy and chemoimmunotherapy for metastatic malignant melanoma: review and
      recent advances.

PMID- 10895161
TI  - Cell phenotype-dependent splicing reflecting differential promoter usage for EBNA
      transcripts in EBV-carrying cells.
AB  - Three types of virus-host cell interactions have been described in cells latently
      infected with EBV: EBNA 1 expression in type I Burkitt's lymphoma cell lines
      (BL), EBNA 1, LMP1 and 2 expression in most nasopharyngeal carcinomas (NPC) and
      EBNA 1-6 with LMP 1 and 2 expression in group III BL-lines as well as
      lymphoblastoid cell lines (LCL). Two group I BL lines that express only EBNA 1
      were found to initiate their EBNA 1 mRNA transcription from a promoter in the Bam
      HI Q-fragment. They use a sequence at +210 bp relative to the Fp transcription
      initiation site in group I BL cell lines. The Fp promoter-region seems to be
      activated in the lytic cycle. LCLs initiate their transcription from one of
      several upstream sites, usually the Cp promoter or, less frequently, one of
      several Wp-promoters. Using RNA-reverse transcription polymerase chain reaction
      (RT-PCR), we have now shown that EBV carrying cells that do not express EBNA 2-6
      always splice their EBNA mRNA at the Q-exon, while EBNA 2-6 positive cells use
      either the Cp or one of the Wp promotors. When EBNA 2-6 are downregulated by
      somatic cell hybridisation between EBNA 1-6 positive B-cell lines and non B-cells
      of hematopoetic, epithelial or fibroblastic origin that express the phenotype of
      the non-B cell parent, the parental usage of Cp/Wp is switched off, and the Q
      exon is activated. NPC cells show the same pattern of promoter usage as the
      hybrids with non-B phenotype. Group III BL cells use both promoter regions. Thus,
      the virus can use two alternative programs, depending on the cell phenotype. The
      "EBNA-1 only" program is activated from the Q-promoter. In cells with an
      immunoblastic (LCL or BL group III) phenotype, the upstream Cp/Wp promoters
      generate a 100 kb. long pre-mRNA, from which all the EBNAs are spliced. As a
      rule, only one of the two programs is used for each phenotype, except for the BL
      group III cells that began as group I but subsequently developed into a more LCL
      like cell. Such cells used both promoter regions, with or without activation of
      the lytic cycle.

PMID- 10895162
TI  - Ameloblastoma of the jaws.
AB  - Ameloblastoma is a histologically benign tumor derived from odontogenic
      apparatus. The tumor can infiltrate into surrounding tissues. Although it is
      benign, it presents symptoms of a malignant tumor, such as infiltration into the
      lungs, pleura, regional and distant metastases, orbit, base of skull, brain and
      has resulted in death. It also has a high incidence of recurrences, the existence
      of regional or distant metastasis, showing a microscopic pattern of ameloblastic
      carcinoma with cytologic features of an increasing nuclear/cytoplastic ratio,
      nuclear hyperchromatism, and the presence of mitosis. We report a study of 12
      patients of ameloblastoma of the jaws between January 1992 and December 1996
      consisting of 8 affected in the mandible and 4 in the maxilla. One patient with a
      tumor in the maxilla was excluded from this study, due to a different
      histological and clinical behaviour of the ameloblastoma.

PMID- 10895163
TI  - Breast conservation therapy--surgical aspects.
AB  - Breast conservation therapy is now accepted as an alternative to mastectomy for
      early stage breast cancer. In 1991 the NIH recommended a regime consisting of the
      excision of a primary tumour with a 1 cm-margin of breast tissue around and an
      axillary node dissection followed by postoperative administration of 45-50 Gy
      irradiation. Although this regime is popular in most centres, several issues
      remain controversial. These are (1) selection of cases, (2) surgical technique,
      (3) histopathology and radiology, and (4) adjutant therapy. In this presentation
      I shall deal mainly with the surgical aspects of breast conservation.

PMID- 10895164
TI  - New development of treatment for locally advanced breast cancer.

PMID- 10895165
TI  - Pathological aspects of brain tumors.
AB  - Brain tumors based on their histogenesis, consist of all tumors, derive from the
      entirely tissue in the intracranial space, both from the neuro-ectodermal/neuro
      epithelial tissue and the mesenchymal tissue. By their location they can be
      divided into infratentorial or supratentorial, and further into deep vs.
      superficial. The interesting and unique, there are age distribution or location
      sex specificity of some brain tumors (BT). WHO Histopathological Typing of Tumors
      by the CNS, also showing progress on both of their members and new special types
      of some BT, especially for the meningiomas and neuro-epithelial/neuroglial type.
      Periodic investigations by the Department of Anatomic Pathology, the Faculty of
      Medicine, University of Indonesia did not show major changes in their BT types,
      but there was on their tumors ranging. Astrocytoma (including glioblastoma
      multiforma) for a while was replaced by meningioma as the most common
      CNS/Intracranial tumor. There are some techniques for the handling of CNS
      specimens depending on further purposes through on biomolecular activities or
      defects. The routine technique using light microscope examination was the most
      useful one for daily diagnosis for many years. Some immunohistochemistry
      techniques are needed for difficult cases, e.g., GFAP, NE 14, NSE, S100, and MBP.
      Diagnostic problems could be caused by tissue- or cell-sampling errors, which are
      influenced by the tumor location itself. Thus, neurosurgeons encounter problems
      to pick biopsy intraoperative, or by mishandling by the laboratory of anatomic
      pathology. Formerly, as final diagnosis, grading of CNS tumors must be put
      according to the Clinical interest for further management of the patient. CNS
      grading ranges from grade I (benign looking) to IV (malignant). Morphological
      grading is based on Kernohan and Adson (1949), or Kernohan and Sayre (1952).

PMID- 10895166
TI  - Interferon-alpha and cytosine arabinoside therapy in chronic myeloid leukemia.

PMID- 10895167
TI  - Present status and future aspects in radiation oncology.

PMID- 10895168
TI  - High dose rate interstitial brachytherapy for mobile tongue cancer: Part 1. Phase
      I/II study of HDR hyperfractionated interstitial brachytherapy for oral cancer.

PMID- 10895169
TI  - High-dose rate interstitial brachytherapy for mobile tongue cancer: Part 2. Phase
      III trial of HDR versus LDR interstitial brachytherapy for T1-T2N0 carcinoma of
      the mobile tongue.

PMID- 10895170
TI  - High-dose rate interstitial brachytherapy for mobile tongue cancer: Part 3.
      Comparative study of early mucosal reaction and late tongue atrophy between LDR
      and HDR Ir-192 interstitial brachytherapy for patients with carcinoma of the
      mobile tongue.

PMID- 10895171
TI  - Prospective study of external radiotherapy with and without intraluminal
      brachytherapy for esophageal cancer in Japan. JASTRO Study Group.
AB  - To improve the results of treatment of patients with esophageal cancer, it is
      important to achieve good local control. Since the esophagus is adjacent to
      highly radiation-sensitive organs such as the lungs, bone marrow, etc., it is
      difficult to irradiate tumors with high doses. Although irradiation techniques
      have improved as a result of advances in treatment-planning equipment and
      irradiation equipment, there are still some patients for whom radical radiation
      therapy within doses that the bone marrow and lungs can tolerate is difficult
      with external irradiation alone. On the other hand, intraluminal brachytherapy
      allows high-dose irradiation of esophageal cancer with little risk to adjacent
      organs. However, intraluminal brachytherapy, in which the dose sharply declines
      with the distance from the radiation source, is suggested to be a useful
      technique for tumors with relatively shallow invasion. With the aim of improving
      the results of esophageal cancer treatment, we designed this study to establish
      the optimal irradiation method in radical radiation therapy for esophageal cancer
      by clinically evaluating external irradiation alone and in combination with
      intraluminal brachytherapy.

PMID- 10895172
TI  - Endoscopic therapy for early gastric cancers due to radiographic and endoscopic
      diagnosis.

PMID- 10895173
TI  - The prognostic dilemma of nodal micrometastases in breast carcinoma.
AB  - The presence of axillary lymph node metastasis in patients with breast cancer is
      a major prognostic factor and also determines the use of adjuvant chemotherapy.
      Micrometastasis has been arbitrary defined as deposits of < 2 mm dimension.
      Earlier studies of micrometastases failed to demonstrate prognostic relevance.
      However, when larger numbers of patients were followed up for longer periods,
      micrometastasis was shown to be a significantly poor prognostic parameter with
      patients having a survival rate similar to those with macrometastasis or nodal
      disease. There are no compelling reasons to retain the term "micrometastasis" in
      the light of these findings and our understanding of tumor biology. Routine
      histological examination of axillary lymph nodes is a notoriously inaccurate
      method for the detection of metastases. When serial or multilevel sectioning
      and/or immunohistochemical staining for cytokeratin were employed, detection
      rates increased by as much as 33%. Reverse transcriptase-polymerase chain
      reaction and Southern blotting for CK19 may be a more accurate method of
      examination. However, there are inherent technical problems associated with this
      method, and the recent finding of a pseudogene with great homology to CK19 in
      normal peripheral blood nucleated cells further emphasises the need for caution
      in this approach. It is not cost-effective to employ serial sectioning and
      immunohistochemistry when examining the axillary contents. However, the
      introduction of sentinel-node biopsy may allow detailed examination of the single
      node most likely to harbour a metastatic tumor.

PMID- 10895174
TI  - The clinical benefit of the histoculture drug response assay.

PMID- 10895175
TI  - Epstein-Barr virus latent membrane protein 1 (EBV-LMP1) and tumor proliferation
      rate as predictive factors of nasopharyngeal cancer (NPC) radiation response.
AB  - BACKGROUND: Irradiation is still the treatment of choice in NPC treatment as one
      of highest malignancy in Indonesia as well as in Southeast Asia. Up to now there
      is no accurate predictor on radiation response, since that the similar histo
      morphological pattern, as a well-known prognostic factor can revealed a wide
      range of treatment outcomes. Purpose of the study is to established the influence
      of EBV-LMP 1 as the most important protein expressed by EBV oncogenes in cellular
      behaviour such as proliferation rate, tumor aggressivity in NPC and to find out
      the role of both, proliferation rate and EBV-LMP1 expression as a predictor on
      NPC radiation response. MATERIALS AND METHODS: 172 paraffin-embedded biopsy
      specimens from NPC patients were analysed flow-cytometrically to obtain the S
      phase fraction value as the proliferation parameter. From this group of patients,
      81 fresh specimen biopsies could be collected, and the EBV-LMP 1 expression were
      detected by western blotting technique (mAB S12--Karolinska Instituet) could be
      done. Several variables such as clinical stage, pathology pattern and radiation
      response were also collected. The radiation responses were established clinically
      (by nasopharyngoscopy), by CT scanning and pathologically. RESULTS: Sixty-five
      percent of our patients belong to the T3 and T4, whereby the N2-3 group consists
      75% of them. Fourteen percent of the patients are Hsu type I, 48% are Hs type II
      and the rest belong to Hsu type III. Our study revealed that the mean SPF value
      was 14.62% (10.18%, which correlated (p < 0.05) with the tumor and nodal sizes.
      The rate of positive expression of the EBV-LMP1 was 50%, and did not show a
      correlation with the proliferation activity as well as the radiation response.
      However, it showed a significant correlation with the tumor and nodal size. There
      was a significant correlation between this proliferation value with the radiation
      response calculated by both, bivariate as well as by multivariate analysis. The
      complete and incomplete response group of patients has a SPF mean value of 10.1%
      +/- 9% and 17.1% +/- 9.3% respectively, with the SPF cut off value of 11%. There
      is no correlation between the proliferation rate with the histology pattern of
      NPC, as well as this radiation response with the histology pattern. CONCLUSIONS:
      It is assumed that the expression of EBV-LMP1 prevents the apoptosis process
      through increasing the level of A20 protein, rather than inducing the expression
      of the EGFR in the proliferation pathway. SPF, one of the proliferation rate
      parameters, was the only factor that can be used as a radiation response
      predictor of NPC. It is assumed that the patients with high proliferation rate
      (SPF > 13%) should be irradiated in the unconventional irradiation scheme such as
      hyper-fractionated irradiation, or combined with another modality that will
      enhance the radiation effect, since the proliferation is too fast for once-a-day
      irradiation scheme. There were no correlations among pathology pattern, the
      proliferation rate and radiation response in NPC.

PMID- 10895176
TI  - Diagnostic imaging of hepatocellular carcinoma in interventional radiology.

PMID- 10895177
TI  - Recent advances of molecular biology in colorectal cancer.

PMID- 10895178
TI  - Preliminary experiences in tracheobronchial stent application for airway
      stenosis.

PMID- 10895179
TI  - Pathology of nasopharyngeal carcinoma.

PMID- 10895181
TI  - Chemotherapy of advanced or recurrent cervical carcinoma with a consecutive low
      dose cisplatin combined with bleomycin, vincristine, and mitomycin-C (consecutive
      low-dose BOMP).
AB  - There are many problems encountered in devising chemotherapy for patients with
      advanced or recurrent cervical carcinoma, in part because the vast majority of
      such patients have received prior radiation therapy with or without radical
      hysterectomy. Prior radiation therapy not only impairs bone marrow reserve but
      also interferes with the vascular supply to the tumor bed and delivery of the
      drug. In addition, many of the patients with advanced or recurrent cervical
      carcinoma have ureteral obstruction with impaired renal excretion of certain
      agents, thus limiting the tolerance to these agents. Despite these problems,
      there is considerable information regarding the chemosensitivity of this disease,
      and there is no doubt that cervical carcinoma is sensitive to platinum compounds.
      The authors have designed a new chemotherapy protocol utilizing a consecutive low
      dose cisplatin to overcome the above difficulties. This review article includes
      the results of this regimen for recurrent or persistent cervical carcinoma and
      the preliminary data obtained from patients with advanced cervical carcinoma
      receiving this regimen in a neoadjuvant setting.

PMID- 10895180
TI  - Intraperitoneal chemotherapy and intraperitoneal washing cytology in management
      of ovarian cancer.

PMID- 10895182
TI  - Results of the clinical trial of transdermal therapeutic system-fentanyl in
      strong opioid pre-treated adult patients with cancer-related pain.

PMID- 10895183
TI  - Preoperative chemo- and radiotherapy in locally advanced esophageal cancer.

PMID- 10895184
TI  - Preoperative therapy for local-regional gastric cancer: rationale and review of
      trials.
AB  - The standard approach for patients with local-regional gastric carcinoma is an
      attempted surgical resection to achieve a "curative resection" (also called an R0
      resection) with adequate lymph node dissection. Western patients, who often get
      suboptimal surgery and have a high incidence of regional lymph node involvement,
      remain at higher risk of local and systemic relapse after an R0 resection than
      most Japanese patients. Numerous postoperative adjuvant therapy trials have not
      yet established an advantage for these patients. Thus in the West, the concept of
      preoperative therapy is appealing. The preoperative approach can potentially
      result in downstaging (or downsizing) of the primary tumor and, therefore,
      increasing the rate of R0 resection. Investigators are still refining the
      treatment strategies and defining ideal patient population for this approach.
      Undoubtedly, properly designed prospective randomized trials will be needed to
      establish any advantage with this approach. A number of newer agents hold a great
      deal of promise.

PMID- 10895185
TI  - Chemotherapy of metastatic gastric cancer.

PMID- 10895186
TI  - Intermittent hormone therapy: its potential in early prostate cancer and intra
      epithelial neoplasia.
AB  - This paper reviews results from a pilot study of 40 patients entered on
      intermittent hormone therapy having achieved a PSA complete remission. The median
      time to clinical progression and need for further hormone therapy was 14 month;
      and 88% of patients retreated are progression-free at 1 year and an overall 88%
      are alive at 3 years. There was some evidence that there was slower progression
      to require treatment in older patients and those who had been on treatment for
      more than 15 months. Since the overall survival in this study is better than that
      of patients with M0 disease on hormone therapy in the immediate arm of the MRC
      immediate vs. deferred therapy study, it is thought reasonable to justify
      progression to a randomised trial. This should also include all patients failing
      to achieve PSA complete remission in order to examine the issue of whether
      androgen withdrawal is required in the terminal treatment phase of hormone
      resistance patients to keep the hormone sensitive clone under control.

PMID- 10895187
TI  - The plausibility and promptness of some pathological aspects of breast cancer.
      "DHARMAIS" NCCH.
AB  - Breast Cancer (BC) still interest to be discussed, comparison studies from
      several investigators still in controversial, especially on risk factors of BC,
      otherwise BC morbidity and mortality were stationary, infact, had a tendency
      increasing. Epidemiology studies on BC, daily observation for a long period
      explored that some Indonesian BC cases from different areas were young, plenty of
      the Indonesian BC cases were admission to hospital in a late stage (TNM III-IV).
      Western style of life influences on diet, cooking, breast feeding, smoking, etc.
      Recent studies on bimolecular sciences gave so much hopes on a large scope of
      human being-non human being, though there were also some threatenings and
      confusions. On Pathology Molecular, there were so many bimolecular techniques
      approached to search what was the exactly happening in cellular level of some
      diseases; so do on carcinogenesis. Searching intracellular abnormalities could be
      divided into: cellular membrane level, cytoplasmic level, nucleic membrane level,
      and intranucleus (DNA, RNA) level. Formerly, cytology and histopathology
      examination had only emphasized the morphological appearances of varied
      pathological lesions, included Cancer-BC. Recently there were new techniques
      worldwide well established, well known. Which one we will choose for BC? Benefit?

PMID- 10895189
TI  - Pathological diagnosis of bone sarcoma.
AB  - The diagnosis of bone lesions should be established in every case by combined
      clinical, radiologic and pathologic investigations. For pathologic investigation,
      a surgical biopsy or needle biopsy should be carried out. Before attempting to
      make a diagnosis, the pathologist must determine that the tissue to be studied is
      representative. If clinical and radiologic information is not readily available,
      the pathologist must insist on its submission before rendering a diagnosis on a
      slide. It is said that to merely "read slides" without full comprehension of the
      clinical setting and the radiologic clues of the biologic behavior of the tumor
      can easily lead to an erroneous diagnosis. A specimen from aspiration biopsy is
      generally adequate for immediate diagnosis for some bone tumors, but in many
      cases it is not sufficient for accurate classification of either benign or
      malignant tumors.

PMID- 10895188
TI  - Dietary macro/micro-nutrients as a breast cancer risk: findings from nutritional
      case-control study in Jakarta, Indonesia.

PMID- 10895190
TI  - Perioperative high-dose rate hyperfractionated brachytherapy for bone and soft
      tissue sarcomas.

PMID- 10895191
TI  - Effects of cisplatin dose intensity on response and survival for patients with
      unresectable and untransplantable hepatocellular carcinoma: an analysis of 57
      patients.

PMID- 10895192
TI  - Continuous hyperthermic peritoneal perfusion (CHPP) for malignant ascites and
      irresectable intra-abdominal cancer.

PMID- 10895193
TI  - Palliative care in cervical cancer.
AB  - 1. Cervical cancer is the most frequent cancer in females and also the most
      frequent among female genital cancers. 2. Ever though the modality of diagnostic
      procedures for early detection has improved, in fact most of the patients present
      in the late stages, so the disease is already incurable, and palliative care is
      really needed. 3. Palliative care is needed not only for the terminally ill
      patients, but can be started at the time the cancer is diagnosed. 4. Palliative
      care is a multidisciplinary approach requiring teamwork. 5. Palliative care in
      Indonesia, especially in Dr. Soetomo Hospital, is a new modality in the fight
      against cancer, so we suffer many disadvantages, e.g., disability, limitation,
      lack of experience. However, such problems will stimulate the team to learn more.

PMID- 10895194
TI  - Treatment of malignant brain tumors.

PMID- 10895195
TI  - Experience of treatment of lung cancer patients using paclitaxel and carboplatin.
AB  - Nineteen patients with stage III & IV nonsmall cell lung cancer were treated with
      a regimen containing paclitaxel and carboplatin at Dharmais National Cancer
      Center Hospital and Pertamina Central General Hospital, Jakarta, Indonesia. There
      were 14 males and 5 females, the histologic diagnosis being adenocarcinoma in 13
      patients, squamous carcinoma in 5 patients and adenosquamous carcinoma in 1
      patient. Fourteen patients were in stage IV, 4 had stage IIIB, and one had stage
      IIIA disease. The regimen contained paclitaxel 135-200 mg/m2, combined with
      carboplatin 300 mg/m2 or AUC 6 mg/ml.min, given every 3 weeks. Those who
      underwent at least 3 cycles of chemotherapy were followed up until death.
      Objective improvement (PR) was seen in 12 patients or 63%; 2 had stable disease
      (11%) and 5 had progressive disease (26%). Two patients are still alive at 17.5
      months and 19 months after starting chemotherapy. The one-year survival rate was
      58%, and median survival time was 14 months.

PMID- 10895196
TI  - Preliminary report concomitant irradiation and paclitaxel as radiosensitizer to
      increase the operability of unresectable locally advanced breast cancer.

PMID- 10895198
TI  - Lactation and the risk of breast cancer.
AB  - Some factors are suggested to have an association with an increased risk of
      breast cancer, which are called risk factors. Lactation is one of the risk
      factors that still needs to be studied because of conflicting findings in
      epidemiological studies and also uncertainty regarding biologic plausibility. Our
      objective was to study the relationship between lactation and the risk of breast
      cancer. A pair of unmatched case control studies was held among parous women at
      Dr. Soetomo Hospital (general hospital) and some private hospitals in the
      Surabaya municipality. There are 219 (51.9%) cases and 203 (48.1%) controls
      analyzed in this study. Age, age at menarche, regular menstruation and number of
      parity between both groups are not statistical different. When we divided the age
      at menarche (below 13), it was statistically different. The cases consisted of
      more women with menarche below 13 (p = 0.00038). Other factors showing
      statistical differences in the risk of breast cancer between case and control are
      age at first delivery, family history of breast cancer and age at menopause.
      Women who have lactated (more than 4-month duration of breast feeding) show a
      "protective effect" against breast cancer, OR 0.57 (95% CI 0.33-0.99). However,
      there was no clear duration of lactation and the risk of breast cancer. Logistic
      regression analysis showed that lactation was not any independent factor.
      Lactation exerts a "protective effect" against breast cancer. However, the
      duration of lactation did not show an influence in reducing the risk of breast
      cancer, and logistic regression analysis did not show that lactation was an
      independent factor in the risk of breast cancer.

PMID- 10895197
TI  - Clinical update of gemcitabine in pancreas cancer.
AB  - Pancreatic cancer constitutes less than 2% of all cancers diagnosed in Singapore,
      consistent with the proportion described worldwide. About 40% of patients are
      diagnosed when the disease is locally advanced but without metastases. Another
      40% are diagnosed with distant metastases. Only 20% are diagnosed when
      resectable. Most are adenocarcinomas arising from the head of the pancreas.
      Systemic chemotherapy is used for advanced metastatic pancreatic cancer but has
      met with limited success. Gemcitabine is a new fluorine-substituted cytarabine
      compound. In a randomised study it appears to confer statistically significant,
      although modest, improvement in quality of life and survival of patients with
      metastatic pancreas cancer. Evaluation of the drug in combination chemotherapy
      regimens and with radiation continues.

PMID- 10895199
TI  - Chromosome abnormalities in acute myeloid leukemia: a cytogenetic study in an
      Indonesian population.

PMID- 10895200
TI  - Telomerase activity in different clinical staging of colorectal adenocarcinoma.
AB  - Increased telomerase activity is proposed to be related with the proliferation of
      some gastrointestinal cancers, including colorectal adenocarcinoma. To date,
      little is known about the activity of telomerase in different clinical stagings
      of colorectal adenocarcinoma, which may reflect its association with the
      progression of colorectal adenocarcinoma. We will examine the activity of
      telomerase enzyme in different clinical stagings of colorectal adenocarcinoma to
      know whether it has diagnostic and prognostic value as a tumor marker in the
      management of colorectal adenocarcinoma. The telomerase activities of primary
      tumor and normal adjacent mucosa in 17 cases with different clinical stagings of
      colorectal adenocarcinoma were measured by TRAP assay during the period of 28
      September 1998 to 28 February 1999. The activities of the enzyme were measured
      both qualitatively and quantitatively, and the diagnostic value was assessed by
      diagnostic test using 2 x 2 table contingency. The association between telomerase
      activities and other related factors were assessed by multivariate analysis.
      Increased telomerase activities were found in 82.4% (14/17) of colorectal
      adenocarcinoma, but in only 23.5% (4/17) of normal adjacent mucosa, which was
      significantly higher (p = 0.008) compared to that of normal mucosa. The mean
      values of telomerase activity between different clinical stagings were 0, 0.661,
      and 1.449 units/410 (g protein for Dukes' stage B, C, and D, respectively, which
      gave p value of 0.025 with ANOVA. Using a cut off level of 0.2-units/410 (g
      protein for positive activity, we revealed that the accuracy, sensitivity, and
      specificity were 77.77%, 82.35%, and 76.47%, respectively. There was no
      association found between the histopathologic grading of the tumor and telomerase
      activity. Increased telomerase activity was found in colorectal adenocarcinoma
      compared to the adjacent normal mucosa. Telomerase activity correlates well with
      the progression of colorectal adenocarcinoma. Therefore, telomerase enzyme may
      have a potential diagnostic and prognostic values in the management of colorectal
      adenocarcinoma.

PMID- 10895202
TI  - A profile of DNA ploidy status and proliferative activity of solid tumors.

PMID- 10895201
TI  - Preliminary results of multicenter phase II trial of docetaxel (Taxotere) in
      combination with doxorubicin as first line chemotherapy in Indonesian patients
      with advanced or metastatic breast cancer.
AB  - RATIONALE: Docetaxel and doxorubicin have produced a high degree of activity in
      previously untreated/treated patients with metastatic breast cancer (MBC). The
      efficacy of Taxotere (T) single agent as 2nd line chemotherapy is well
      established in large randomized phase III studies. OBJECTIVE: The objective of
      this study is to confirm the efficacy and safety of a combination of Taxotere
      with doxorubicin as 1st line chemotherapy in Indonesian MBC patients. TREATMENT
      AND METHOD: Eighteen patients age < or = 70 years with advanced or metastatic
      breast cancer (MBC) with no prior taxane chemotherapy or prior cumulative
      doxorubicin (D) of no more than 250 mg/m2 and no heart disease were enrolled in
      this phase II study of D (50 mg/m2) IV bolus followed one hour later by Taxotere
      (T) 60 mg/m2 IV infusion over 1 hour every 3 weeks for 6 cycles treatments. A 3
      day oral corticosteroid premedication was administered starting one day before
      the infusion of each cycle. Left ventricular ejection fraction (LVEF) was
      evaluated at baseline and after cycle 6. PATIENTS CHARACTERISTICS: 18 patients
      (pts) have been treated with 108 cycles administered. Median age was 46 years (31
      58), WHO PS 0 = 50%, 1 = 50% and number of organs involved were: 2 (72%), 3 (22%)
      and 4 (6%). RESULTS: After 3 cycles, partial (PR) and no change (NC) responses
      occurred in 15 pts (83.3%) and 3 pts (16.7%). The best overall response after 6
      cycles, including complete (CR) and partial (PR) responses, occurred in 13 pts
      (72.2%) including 3 CRs and 10 PRs. Two patients with extensive liver metastases
      at the baseline had a complete disappearance after 6 cycles. No patients
      developed congestive heart failure (CHF). Grade 3/4 hematological toxicities
      included leukopenia in 18 pts (100%), febrile neutropenia in 6 pts (33%),
      leukopenia with infection in 2 pts (11%), leukopenia with fever in 1 pt (5.5%),
      and anemia in 6 pts (33.3%). Nonhematological toxicities grade 3/4 included
      alopecia (61%), asthenia (4.6%), nausea/vomiting (2.7%), pain (2.7%), stomatitis
      (2.7%), and diarrhoea (0.9%). Leukopenia was generally of short duration,
      occurred mainly during the first and second cycle, and did not require any dose
      reduction. There was one death due to progressive disease after six cycles of
      treatment. CONCLUSION: Taxotere--doxorubicin combination is very active in the
      first-line treatment of MBC, seems to be especially effective in patients with
      liver metastases, and is associated with a manageable toxicity profile.

PMID- 10895203
TI  - A higher PSA-density cut-off level in patients with intermediate PSA values for
      the early detection of prostate cancer.
AB  - The use of PSA-density (PSAD) as an indicator for prostate biopsy at intermediate
      PSA values has generated controversy. There are investigators who consider that
      the determination of PSAD is futile, and that it is better to do a prostate
      biopsy based on PSA values alone, TRUS (Transrectal Ultrasound) findings and/or
      DRE examinations. Asian countries, especially in the Far East, are considered to
      have a low incidence of prostate cancer (PCa). However, based on western
      references, we still measure PSA-density with a cut-off level of 0.15 to promote
      prostate biopsy in patients with intermediate PSA values (4.1-10.0 ng/ml). Our
      study aims to evaluate the usefulness of PSAD as an indication for biopsy in
      patients with intermediate serum PSA values. To evaluate the usefulness of this
      indicator, we conducted a retrospective study of 132 uncatheterized (to minimize
      potential bias) BPH and PCa cases that were hospitalized in our department
      between 1995-1997 (3 years). This group comprised 127 BPH and 5 PCa patients.
      Mean age was 66.1 +/- 7.69 years; mean PSA was 7.92 +/- 9.289 ng/ml; mean
      prostate volume was 54.1 +/- 26.72 cc; mean PSAD was 0.15 +/- 0.185. More
      specifically, there were 49 patients with intermediate PSA values (47 BPH & 2
      PCa). The receiver operator characteristic (ROC) curve revealed an optimum cut
      off level of 0.19. At this level of PSA density, the measured sensitivity was
      100% with a specificity of 79%. We concluded that, in our uncatheterized patients
      (without retention) series, the PSAD cut-off level for prostate biopsy (0.19) was
      higher than that in the western world (0.12 or 0.15).

PMID- 10895204
TI  - Monoclonal immunoglobulins in serum and urine specimens from patients with plasma
      cell disorders.

PMID- 10895205
TI  - Combination chemotherapy of continuous 5-FU infusion and low-dose cisplatin
      infusion for the treatment of advanced and recurrent gastric and colorectal
      adenocarcinomas.
AB  - We evaluate the efficacy and toxicities of low-dose FP therapy in the treatment
      of advanced and recurrent gastric and colorectal adenocarcinomas. 104 patients
      (gastric adenocarcinoma: 52, colorectal adenocarcinoma: 52) were enrolled. Low
      dose FP therapy consisted of 5-FU (160 mg/m2/day every day by continuous
      infusion) and cisplatin (3 mg/m2/day in 100 ml of normal saline by infusion over
      30 minutes on days 1-5/W). Patients were treated for 4 consecutive weeks with
      subsequent one-week rest period. Ninety-four of 104 patients completed this
      therapy, and the treatment accomplishment rate was 90%; 82% in gastric
      adenocarcinomas, 96% in colorectal adenocarcinomas. Two cases had CR, and 47
      cases had PR, with an overall response rate of 52.1%. Response rates, 50%
      survival time, 1-year survival rates, and 2-year survival rates were 65.9%, 249
      days, 33.7%, 19.7% in gastric adenocarcinomas, and 40.0%, 466 days, 56.7%, 29.4%
      in colorectal adenocarcinomas, respectively. Nausea/vomiting was the most common
      toxicity, occurring in 44.2% of patients treated and was predominantly mild to
      moderate (up to Grade 2). In 5 cases Grade 3 toxicity was observed. Low-dose FP
      therapy has a high antineoplastic effect and low-grade toxicity, and this therapy
      should become the first-choice chemotherapy for the treatment of advanced and
      recurrent gastric and colorectal adenocarcinomas.

PMID- 10895206
TI  - Exenteration of the orbit by the oncology rule.
AB  - The operation of malignant tumors must follow the rule of oncology procedure. The
      fact is very important to avoid complications in the short- or long-term. The
      complication in the short term is bleeding during the operation, and the
      complications in the long-term are: metastasis of the tumor and locally recidive.
      Metastasis is of the tumor can occur because of the opening of the vessels, so
      that particles or microparticles of the tumor can enter into the lumen of the
      artery or the vein. However, this can also happen by the lymphatic route. If the
      operating procedure follows the rule of oncology, we hope that the tumors will be
      completely eradicated, complications will be much reduced, and the survival rate
      of the patient also increases. Metastasis and other complications can occur more
      rapidly after tumor surgery. Many steps can be taken to avoid such complications.
      One of them is to operate on the tumor by observing the oncology rule. The aim of
      this paper is to avoid the complications of surgery by following the oncology
      rule. Steps that must be taken before the operation are: biopsy of the tumor;
      staging; consultation with medical oncologists and radiology oncologists, and
      then the resection of the tumor if necessary.

PMID- 10895207
TI  - Experience in detecting p53 mutation in various malignancies using single-strand
      conformation polymorphism (SSCP) technique applied on Phast-System.

PMID- 10895208
TI  - Biclonal gammopathy in multiple myeloma: a case report.
AB  - Monoclonal gammopathy is a group of B-cell disorders which result in the
      production of a specific and unique monoclonal immunoglobulin (M-component).
      Biclonal gammopathy is characterized by the simultaneous appearance of two
      different M-components. The incidence is about 1% of all monoclonal gammopathy.
      This paper reports on a 48-year-old male who had a chief complaint of back-pain
      beginning 7 months earlier. A physical examination was unremarkable, except for
      anemia and tenderness in the back. Hemoglobin was 5.4 g/dl, white blood cells 4.5
      x 10(3)/microliter, platelets 157 x 10(3)/microliter, and reticulocytes 0.9%.
      Serum iron was 79 mg/dl, and total iron-binding capacity was 210 mg/dl. A blood
      smear showed the formation of rouleaux, but no plasma cells were found. Serum
      creatinine was 5.4 mg/dl, with a creatinine clearance of 18.1 ml/min. Serum
      electrolytes were normal except for serum calcium which was 14.4 mg/dl. The
      urinalysis showed strongly positive proteinuria (+2), with negative Bence Jones
      protein. Serum protein electrophoresis showed an increase and a spike pattern of
      beta-2 globulin (2.8 g/dl) and alpha-2 globulin (1.5 g/dl), with normal gamma
      globulin. By nephelometry technique, serum IgG was normal (1388 mg/dl), IgA was
      high (900 mg/dl), and IgM was also high (517 mg/dl). Advanced and extensive
      osteolytic lesions were found in the clavicle, ribs, skull, humerus, femur, and
      columna vertebralis. Plasma cells (myeloma cells) in bone marrow were 32%. The
      clinical diagnosis was multiple myeloma (biclonal gammopathy) stage IIIB (Durie
      and Salmon staging system). Clinical response was good after two series of
      conventional chemotherapy, with normal serum electrophoresis, decreasing serum
      creatinine and serum calcium. Based on the above data, the diagnosis of multiple
      myeloma with biclonal gammopathy was confirmed. This is a rare case with a
      combination of IgA and IgM M-components.

PMID- 10895209
TI  - Cancer in Cipto Mangunkusumo Hospital, Jakarta.

PMID- 10895210
TI  - Paclitaxel (T) and carboplatin (CB) in ovarian cancer patients in Dharmais
      National Cancer Hospital, 1993-1999.

PMID- 10895211
TI  - Rationale for using serum prostate-specific antigen (PSA) level and PSA density
      (PSAD) to detect prostatic malignancy in a country with low prostate cancer
      incidence.
AB  - Prostate-specific antigen (PSA) and PSA density (PSAD) values in Indonesia had
      been found uniquely much higher than the normal accepted values in western
      countries. However, PSA more than 10 ng/ml and PSAD above 0.15 in intermediate
      PSA of 4-10 ng/ml are still indicative of a prostate biopsy. This condition had
      led to unnecessary biopsies in view of the low incidence of prostatic carcinoma
      in our country. Our objective is to find alternative serum PSA levels and PSAD
      cutoff points that enhance the specificity and sensitivity of prostate cancer
      detection. This retrospective cross-sectional study included 805 consecutive
      patients from 40 to 95 years old in Sumber Waras Hospital (SWH) and Cipto
      Mangunkusumo Hospital (CMH) from 1994 to 1997. All patients underwent digital
      rectal examination (DRE) and transrectal ultrasonography (TRUS) to measure
      prostate volume. After the serum PSA level was determined and PSAD was
      calculated, prostate biopsies were performed if the PSA level was greater than 10
      ng/ml or PSAD more than 0.15 at intermediate PSA levels of 4-10 ng/ml. The
      ability of PSA, intermediate PSA level, and PSAD to improve the accuracy of
      prostate cancer detection was evaluated using univariate analysis. Among 805
      patients, 240 patients had PSA level < 4 ng/ml, 230 patients had PSA level 4-10
      ng/ml, and 335 had PSA level > 10 ng/ml. Of the 230 patients with intermediate
      PSA level, 108 had PSAD > 0.15. Thirty-five patients had histologically confirmed
      prostatic carcinoma, i.e., 3 of 108 patients with PSA 4-10 ng/ml and PSAD > 0.15,
      and 32 of 335 patients with PSA > 10 ng/ml. There were 105 and 303 unnecessary
      biopsies in those groups. With a PSA cutoff level of > or = 8 ng/ml, we found
      100% sensitivity to prostate cancer. PSAD > or = 0.20 within a PSA level of 8-30
      ng/ml gave 100% sensitivity to prostate cancer. Using these new cutoffs there
      would be 148 biopsies (33.4%) saved. We concluded from this study that the
      commonly accepted values of serum PSA level and PSAD resulted in many unnecessary
      biopsies in our patients. Instead, the most sensitive cutoff points to perform
      prostate biopsy are serum PSA level greater than 8.0 ng/ml, and PSAD of more than
      0.20 at an intermediate serum PSA level of 8-30 ng/ml.

PMID- 10895212
TI  - Intramedullary oligodendroglioma: a case report.

PMID- 10895213
TI  - Spontaneous total regression of suspected metastatic brain tumor: what to do
      next? A case report.

PMID- 10895214
TI  - Role of magnetic resonance imaging (MRI) in early cervical cancer.
AB  - The aim of this study was to prospectively determine if invasive carcinoma of the
      cervix can be ruled out by negative magnetic resonance image (MRI) findings.
      Eligible patients were those who were scheduled to undergo either hysterectomy or
      conization because of invasive or non-invasive lesions of the cervix. T2-weighted
      and T1-dynamic enhancement images were reviewed by two radiologists who had no
      information on these patients except for the preoperative diagnosis. Clinical
      information regarding location of the disease was not given. At least 12
      longitudinal sections prepared from the surgically removed cervix were reviewed
      by a pathologist who was not provided with MRI information. The correlation
      between MRI and histological findings was analyzed in terms of depth of invasion.
      Seventy cases were entered and 66 were evaluable. Sensitivities of T2 and dynamic
      MRI for invasive and non-invasive disease by radiologist 1 were 0.8824 and
      0.8235, respectively, and those by radiologist 2 were 0.6296 and 0.7647,
      respectively. Specificities were 0.8776 and 0.8571, respectively, for radiologist
      1 and 0.8974 and 0.8367, respectively, for radiologist 2. When sensitivities and
      specificities were calculated for prediction of non-invasive plus microinvasive
      lesions < or = 5 mm vs. invasive lesions > 5 mm, specificities of T2 and dynamic
      MRI became 1.0000 for both radiologists. Negative findings on T2 and/or dynamic
      MRI indicated non-invasive or early invasive cervical diseases < or = 5 mm. The
      dynamic technique provided only limited additional value in the detection of
      early invasive cervical carcinoma.

PMID- 10895215
TI  - Knowledge and attitude concerning cigarette smoking among schoolchildren in
      central Jakarta.

PMID- 10895216
TI  - The role of low dose cisplatin plus 5-fluorouracil for treatment of recurrent
      and/or advanced squamous cell carcinoma of the head and neck.
AB  - To improve survival rate in advanced head and neck cancer, we scheduled 90
      patients to receive low dose cisplatin plus 5-fluorouracil regimen as
      neoadjuvant(NAC), concurrent(CC), adjuvant(AC), and second line chemotherapy (SC)
      setting. Our regimen consisted of cisplatin (CDDP 5 mg/m2/1 hr infusion on days 1
      5, 8-12, 15-19, 22-26) and 5-fluorouracil (5-FU 200 mg/m2/24 hr infusion or oral
      administration of tegaful-uracil (UFT-E) 400 mg/body on days 1-28). The
      concurrent chemoradiotherapy consisted of conventional irradiation with 1.6-2.0
      Gy/day on five days per week up to a total dose around 60Gy, and CDDP 3 mg/m2 by
      intravenous infusion over 1 hour plus 5-FU 150 mg/m2 by intravenous infusion over
      24 hours per day on five days per week. For SC, 24 patients evaluable for
      response, 4 CR and 6 PR with RR of 42% were achieved. For NAC, 14 patients were
      evaluated for response, 2 CR and 7 PR were achieved. CC was indicated for locally
      unresectable cases. Of the 33 patients evaluable for response were 17 CR and 9 PR
      with RR of 79%. Dose limiting toxicities for chemotherapy were anemia and
      leukopenia and chemoradiotherapy was mucositis. Our treatment modality showed
      marginal toxicity and good response. Moreover, our regimen could be given in an
      outpatient setting safely so quality of life for patients was identical. We
      concluded that for advanced head and neck cancer, these treatment options were
      effective for second line and adjuvant setting. Chemoradiotherapy with this
      regimen also gave a impact for improving local control and survival period for
      locally unresectable cases.

PMID- 10895217
TI  - Correlation of clinical, pathological status, hormone receptor and C-erbB-2
      oncoprotein in breast cancer patients.
AB  - This study is to evaluate the correlation of some established prognostic factors,
      hormone receptor and C-erbB-2 expression of breast cancer patients in Yogyakarta,
      Indonesia. Beginning January 1997, 60 breast cancer patients who were treated
      either by mastectomy, breast conserving surgery or biopsy, were evaluated
      clinically in connection with age, menopausal status, stage, tumor size, nodes;
      also histologically regarding type, grade and mitotic index. Patients were
      evaluated for estrogen and progesterone receptor, as well as C-erbB-2 expression
      with immunohistochemical techniques. Median age was 47.5 years old, range from 28
      to 80 years old. Most of them were premenopause (65.0%). One patient (1.7%) was a
      man. Most of the patients were stage IIB (25.0%), 51.7% with positive estrogen
      receptor and 65.9% with positive progesterone receptor. The type was mostly
      invasive duct carcinoma, high grade (70.0%). Most of the tumor size ranged
      between 2-5 cm (56.9%), with more than 3 nodes in 38.3% of patients. High mitotic
      index was found in 69.5% and positive C-erbB-2 in 71.7% patients. Correlation of
      C-erbB-2 and other prognostic factors showed that only stage, node and mitotic
      index had significant correlations (p = 0.016; 0.035 and 0.005, respectively). A
      significant correlation was also found between ER and PR level, PR and tumor
      size, stage and tumor size, stage and nodes, tumor size and nodes (p < 0.05), and
      a borderline correlation between ER and tumor size (p = 0.065) in conclusion,
      this preliminary study showed that breast cancer in Yogyakarta had an aggressive
      phenotype. C-erbB-2 positivity was correlated significantly with stage of the
      disease, number of nodes involved and mitotic index. Hormone receptors also
      correlated with some prognostic factors in breast cancer patients.

PMID- 10895218
TI  - Postoperative closed chest drainage without an underwater seal: a preliminary
      report.
AB  - The Aldon's urobag (e.g. simpla S4) which consists of a 2 litre plastic bag with
      a flutter valve and a drainage tube has been used in 29 consecutive cases as a
      postoperative pleural drainage system. The age range of patients was between 2
      months and 74 years (mean 26.7 years). Indications for pleural drainage included
      lobectomy (3 cases), decortication (2 cases), lung biopsy (2 cases). Blalock
      Taussig shunt (5 cases), patent ductus arteriosus patent ductus arteriosus (PDA)
      ligation (1 case), closed mitral valvotomy (1 case), oesophageal surgery (13
      cases) and chest wall resection (2 cases). The period of pleural drainage ranged
      from 1 to 8 days (mean 3.75 days). The only operative death was not related to
      drainage system. No complications were attributable to the drainage system. This
      alternative chest drainage was found to enhance early ambulation, increase the
      efficiency of patient nursing and reduced the cost of consumables.

PMID- 10895219
TI  - Low birth weight and its correlates among Nigerian twins.
AB  - The incidence and correlates of low birth weight (LBW) among an index population
      of 525 newborn Nigerian twins and a control population of 363 singletons were
      studied. The incidence of LBW among the twins (53.9%) was significantly higher
      than the incidence of 11.8% among the singletons (P < 0.001). Smallness for
      gestational age (SGA) was also higher (14.3%) among the twins compared with 1.4%
      among the singletons (P < 0.001). Morbidity factors frequently associated with
      LBW among the twins were perinatal asphyxia, hypothermia, neonatal seizures, and
      intracranial haemorrhage. Intrapartum asphyxia was particularly common in those
      preterm LBW twins who were also SGA. This raises serious concern because of the
      known higher risks of SGA preterm babies for severe neurologic sequelae. Low
      socioeconomic status (SES) of mothers was an important predisposing factor to LBW
      and SGA as well as to premature deliveries among the twins. Improved SES of the
      maternal population and increased awareness by health practitioners of the risks
      LBW twins face, should improve their immediate and later outcome. Furthermore,
      there is a need for the development of an intrauterine growth chart for Nigerian
      twins to enhance accurate diagnosis of LBW and SGA among newborn twins.

PMID- 10895220
TI  - Clinical study of cerebral malaria in African children.
AB  - Of 51 consecutive children with cerebral malaria, fever, convulsions, and
      drowsiness were the commonest presenting symptoms. Decerebrate and decorticate
      postures and absent cornea reflex were the commonest brain stem signs. Opening
      lumbar cerebrospinal (CSF) pressure was raised in all but one of 24 children in
      whom it was reliably measured [mean 15.2 +/- 5.7 mmHg, range 6-24]. Hyponatraemia
      occurred in 17 (33%). Acute renal failure was not uncommon; the combination of
      hypercreatininaemia (plasma creatinine > 100 mumol/L) and hyperkalaemia (plasma
      potassium > 6.0 mumol/L) was fatal in 5 out of 7 patients in whom it occurred.
      Disturbances of acid-base status were present in all 40 children in whom it was
      assessed on admission. Mortality rate was 16% (8 patients). Neurological deficits
      occurred in 7 (14%) of the survivors and included cortical blindness [3], aphasia
      [3], hypertonia [3], hearing loss [2], and dystonia [1]. In addition to the
      present measures aimed at reducing morbidity and morality in children with
      cerebral malaria, efforts should be directed at rapid assessment of renal
      function and prompt correction of such dysfunction if found.

PMID- 10895221
TI  - Health problems and socio-demographic findings in elderly Nigerians.
AB  - Nine hundred and fifty-one persons aged 60 years and over, living at home in four
      locations in southwestern Nigeria were studied. The cohort representing urban and
      rural dwellers, constituted 7.8% of the total population. Female residents had
      higher widowhood rates and lower levels of educational attainment than males.
      Multigenerational living arrangements were popular. Ninety-five percent of the
      cohort had no physical impairment on assessment of activities of daily life. Only
      6.4% were on a regular pension (males more than females, P < 0.001) and income
      for 75% was less than the estimated poverty line (females more than males P <
      0.001). Estimated crude death rate was also higher than the national average. The
      effects of these socio-demographic factors on health are diverse. Comparisons
      were made with similar studies in other cultures.

PMID- 10895222
TI  - Effect of diabetes mellitus on glomerular filtration rate in an urban hospital
      diabetic population.
AB  - Glomerular filtration rate (GFR) as assessed by endogenous creatinine clearance
      was studied in 46 male and 38 female patients with diabetes mellitus (DM). Of
      these, 44 patients had uncomplicated DM (Group I) whilst 40 patients had
      complicated DM (Group II). There were 20 insulin-dependent diabetes mellitus
      (IDDM) patients in Group I and 5 in Group II, and 24 non-insulin dependent
      diabetes mellitus (NIDDM) patients in Group I and 35 in Group II. In Group I, 6
      IDDM and 4 NIDDM patients had supranormal glomerular filtration rate (creatinine
      clearance 125 ml/min) and in Group II 1 IDDM and 6 NIDDM patients had supranormal
      GFR. The presence of diabetic complications and the mode of therapy of the
      diabetic state did not significantly affect the glomerular filtration rate. This
      concludes that glomerular hyperfiltration occurred in both IDDM and NIDDM
      Nigerian patients.

PMID- 10895223
TI  - Polymorph function and cellular immunity in Nigerians with pulmonary
      tuberculosis.
AB  - Polymorphonuclear leukocyte intracellular killing of Staphylococcus aureus and
      chemotactic indices as well as T and B lymphocyte subpopulations were determined
      in 35 healthy controls and 70 Nigerians with pulmonary tuberculosis. The patients
      were radiologically classified into exudative, fibro-cavitary, miliary, and mixed
      lesions groups. Migration inhibition factor (MIF) production and glucose-6
      phosphate dehydrogenase (G-6 PD) levels were also determined in 40 patients and
      20 controls. The polymorph function as shown by chemotaxic and killing index was
      significantly reduced (P < 0.05) in all patients when compared to the controls.
      Reduced G-6-PD levels though found in patients when compared to the controls was
      not significant. A reversal of the T helper/T suppressor ratio was found in all
      tuberculosis patients when compared to the controls as a result of decreased T
      helper cell numbers. T helper cells as well as the MIF index tended to be lowest
      in the miliary lesions group.

PMID- 10895224
TI  - A comparison of the cardiovascular responses to treadmill and bicycle ergometer
      exercise in healthy male Nigerians.
AB  - Cardiovascular responses to maximal exercise testing with treadmill (TD) and
      bicycle ergometers (BE) were compared in 60 healthy male Nigerians aged 20-45
      years. The duration of exercise (DOE), maximal heart rate (MHR), peak systolic
      blood pressure (PSBP), and peak rate pressure product (PRPP) values were higher
      with TD than BE (P < 0.0001). The MHR correlated significantly with the DOE in
      both exercise modes (r = 0.5) but only with age in the TD mode (r = -0.4; P <
      0.05). Twenty of these subjects (aged 20-26 years) were further randomized to
      commence with either TD or BE and afterwards to proceed with the second exercise.
      Haemodynamic responses were significantly higher as submaximal exercise on BE
      than TD, while during maximal exercise these responses were significantly higher
      on TD than BE. The rate of perceived exertion was different for two exercise
      modes. Seventeen subjects (85%) preferred the TD while 3 (15%) preferred the BE
      for their personal physical exercise programme. Factors such as varying exercise
      test responses, exercise mode preference, and rate of perceived exertion should
      be taken into consideration whenever exercise testing or training is required in
      various individuals with or without heart disease.

PMID- 10895225
TI  - The clinicopathological pattern of carcinoma of bronchus and lung in Africa: a 20
      year clinical, histopathological, and autopsy study in Ibadan, Nigeria.
AB  - The clinicopathological pattern of carcinoma of the bronchus at the University
      College Hospital, Ibadan over a 20-year period, 1971-1990, was studied. An
      increased incidence of this disease was observed when compared to the study that
      was carried out in the sixties in the same environment. The reasons for the
      increase in incidence and the pattern of clinical presentation are discussed. The
      findings suggest that increasing industrialization and increased acquisition of
      modern diagnostic facilities are responsible for the increased incidence. The
      factors responsible for the poor response to treatment in the series are also
      discussed.

PMID- 10895226
TI  - The social condition of a cohort of peasant farmers in rural community in
      southwest Nigeria.
AB  - This study focused on the psychosocial condition of a cohort of rural farmers,
      highlighting the social condition of their children, their life style, life
      events in the past year, the extent of their involvement in farming, the
      sufficiency of material sustenance from their products, their unmet needs and
      social aspirations, difficulties encountered in farm work, satisfaction with
      farming, and psychological distress. In 1992, 186 farmers were interviewed during
      health education visits at farm villages in Idere town, Oyo State. There were 161
      (87%) males and 25 (13%) females mean age 49.9 (sd 11.7) years: who were
      illiterate, mainly polygamous, with 4-6 children per household. Only two families
      had a child each in institutions of higher learning. The general picture that
      emerged was that of a peasant, hardworking (six-day per week) farmer who relaxes
      with a game of cards in the evenings. His greatest problem is that of
      transportation and hiring extra hands for work. He is impressed by the yield from
      his farm. Compared with urban junior civil servants, the farmers had
      significantly lesser life events and GHQ-12 (psychological symptoms) scores. They
      had unmet social needs and were not satisfied with their condition of living.
      Meeting some of the basic needs of these farmers will boost their morale, enhance
      yield, and lower prices of food for the general population.

PMID- 10895227
TI  - Ferritin and serum iron levels in adult patients with sickle cell anaemia at
      Ibadan, Nigeria.
AB  - The ferritin and serum iron levels in 100 adult patients with sickle cell anaemia
      (SCA) and in ten pregnant (SCA) females were measured. All the adult sickle cell
      anaemia patients had serum ferritin levels ranging between 325 ng/dl and > 1500
      ng/dl. These levels are within and above the normal range. The same trend was
      observed in the pregnant adult females with SCA. However, in the pregnant women,
      significantly lower ferritin levels than in the non-pregnant women were recorded.
      There is, therefore, a reduction in ferritin levels in pregnancy. This could be
      due to the increased iron requirements and demand by the developing foetus. Serum
      iron was below normal in 30% of the pregnant women, only 6% of all the adult
      patients had serum iron levels below the normal levels. Given the adequacy of
      ferritin levels in the patients studied and the very low incidence of below
      normal serum iron levels, it is concluded that the sickle cell anaemia patients
      in the area of study have adequate levels of iron and ferritin in their serum.
      Iron should therefore be given only in proven cases of iron deficiency anaemia.

PMID- 10895228
TI  - The prevalence of isolated sleep paralysis among a sample of Nigerian civil
      servants and undergraduates.
AB  - The study investigated the prevalence of isolated sleep paralysis (ISP) among
      workers; and the relationship between examination stress and ISP among 183
      undergraduates in the week of examination, compared with 61 control students. The
      correlation between ISP experience and psychological distress and distressing
      life conditions was explored using Goldberg's General Health Questionnaire (GHQ
      12) and a life events scale. It was found that 153 (35.5%) subjects admitted
      having ISP at least twice in the past year. There was no significant difference
      in prevalence between workers and students. There was non-significant tendency
      for students under examination stress to report higher frequencies of ISP. ISP
      was significantly associated with GHQ-12 and life events scores. The findings are
      similar to African-American reports. An illustrative case was cited to support
      the psychoanalytic view of ISP as a manifestation of an inhibition that serves to
      ward off forbidden impulses. It is hoped that the awareness of ISP promoted by
      these studies will empower therapists to help people who suffer from the psychic
      distress associated with ISP whilst demystifying the enigma of ISP among those
      who seek help at religious faith healing centres, where supernatural beliefs
      concerning ISP are encouraged.

PMID- 10895229
TI  - High dietary calcium attenuates the enhanced vasoconstrictor effects of serum
      from salt-loaded rats.
AB  - The effect of calcium supplementation and salt loading on blood pressure, serum
      electrolytes, and vasoconstrictor response to serum and vascular prostaglandin
      synthesis were studied in Sprague Dawley rats. The mean arterial pressure of salt
      loaded rats was higher (P < 0.05) than the mean arterial pressure of normal rats,
      salt-loaded-calcium-fed rats, or calcium-fed rats. Serum from salt-loaded rats
      had lower serum potassium (4.47 +/- 0.39 Meq/L) and salt-loaded-calcium-fed rats
      (5.14 +/- 0.47 Meq/L). The vasoactivity of serum from the salt-loaded rats
      (1116.67 +/- 160.13 mg) was higher than the contraction produced by sera from
      normal rats (643.80 +/- 37.50 mg) or from salt-loaded-calcium fed rats (562.47 +/
      37.50 mg). Indomethacin did not alter the contractile response of aortae from
      normal rats and salt-loaded rats to noradrenaline, but it significantly enhanced
      the contractile response of aortae from salt-loaded-calcium-fed and calcium-fed
      rats. The results suggest that dietary calcium may lower blood pressure by
      reducing the circulating levels of some plasma vasoactive factors induced by salt
      loading and by enhancing the synthesis of vasodilator prostaglandins.

PMID- 10895232
TI  - Surgery of toxic goitre in non-euthyroid patients: a preliminary report.
AB  - In recent years, the cost of medical care has skyrocketed and since medical
      treatment is not free, some drugs are now beyond the reach of some patients. One
      of such drugs is the antithyroid drug, carbimazole, which has been priced beyond
      the reach of our thyrotoxic patients. We have therefore been forced to operate on
      these patients whenever they present, even while thyrotoxic. The principle of our
      management is to anticipate the development of thyroid crises and to prevent its
      occurrence post-operatively by using saturated solution of potassium iodide
      (SSKI) or Lugol's iodine, propranolol, diazepam, and hydrocortisone. This is a
      preliminary report of the first twelve consecutive patients so treated.

PMID- 10895230
TI  - Outbreak of neonatal Klebsiella septicaemia: a review of antimicrobial
      sensitivities.
AB  - A 10-week prospective study was undertaken to document the antibiotic
      susceptibilities of klebsiella organisms which were responsible for an outbreak
      of septicaemia on the neonatal units of the University College Hospital, Ibadan,
      Nigeria. The thirty-nine isolates obtained comprised K. pneumoniae, 18 (46.2%),
      K. aerogenes, 17 (43.6%), K. edwardsii, 3 (7.7%), and K. oxytoca, 1(2.5%). All
      the strains were sensitive to ciprofloxacin and ofloxacin, but resistant to
      ampicillin. The percentage of qualitative sensitivities of the klebsiella species
      to other available drugs were 41% for ceftazidime, 36% for cefotaxime, 31% for
      ceftriazone, 23% for cefuroxime, 21% for gentamycin, and 15% for kanamycin.
      Quantitative sensitivities of the three most commonly isolated sub-types to
      netilmycin were 63%, 36%, and 33%, respectively. A comparison with a previous
      antibiotic susceptibility study still showed persistent resistance to the
      available aminoglycosides.

PMID- 10895233
TI  - Interrelationship in nutrient intake of Nigerian mothers and their children:
      nutritional and health implications.
AB  - This study examined the interrelationships in the nutrient intake of mothers and
      their children. One hundred and eight mother-child pairs participated in the
      study. The children were aged 36-59 months (mean age 44 months) while the mean
      age of the mother was 31.0 years. The subjects were drawn from rural locations,
      were largely illiterate, and farming and petty trading were main occupations.
      Intakes of energy, protein, total fat, and iron were assessed from 3 consecutive
      24 hour recalls given by the mothers. There were significant positive
      correlations between energy, total fat, and iron intakes of mothers and their
      children. There was no significant correlation in protein intakes of mothers and
      children. The results also indicate that total fat and protein make little
      contribution to the total energy intake of the subjects. Mother's age was
      significantly correlated with child's protein intake (r = 0.21, P < 0.01) but not
      with child's energy, total fat, or iron intakes. Although mother's energy intake
      was significantly correlated with child's energy intake (r = 0.39, P < 0.001)
      this was not the case with the intakes of the other three nutrients. The results
      indicate aggregation of nutrient intakes in mothers and their children which has
      important nutritional and health implications.

PMID- 10895231
TI  - Acceptability of prenatal diagnosis of sickle cell anaemia by a sample of the
      Nigerian population.
AB  - The acceptability of prenatal diagnosis (PND) as a means of controlling sickle
      cell anaemia (SCA) in Nigeria was examined using a semi-structured questionnaire.
      The aim of the study was to examine the attitudes of well-informed, educated
      Nigerians to the use of PND and abortion of confirmed HbSS pregnancies in the
      control of SCA. There were 433 respondents comprising 204 males and 210 females
      (gender was not recorded for 19 respondents). They were aged 15-50 (31 +/- 18)
      years. Forty percent had HbAA, 15% HbAS, 1.6% HbAC, 2% HbSS, and 0.2% HbSC; 153
      (35%) had no knowledge of their haemoglobin electrophoretic patterns "genotypes".
      The majority of the respondents (69.5%) appreciated the role of both parents in
      the transmission of the disease. Only 45 (18%) of the respondents heard of SCA
      for the first time through sickle cell counsellors, 23% through newsmedia, 29%
      through friends and relations, 21% obtained the information through health
      workers, while 5% had never heard of sickle cell disease before the interview. As
      many as 192 (44%) of the respondents were aware that SCA could be diagnosed in
      pregnancy; 45% would opt for termination of the affected pregnancies. Avoidance
      of the problems associated with managing SCA children was the most important
      reason for approving pregnancy termination, whereas 73% of those rejecting
      pregnancy termination did so for religious and moral reasons. Seventy-eight
      percent of those interviewed would want PND started in Nigeria. The two approved
      control measure for SCA by most of the respondents were genetic counselling and
      PND; both should, therefore, be considered in implementing control measures for
      SCA in this country.

PMID- 10895235
TI  - The epithelium of the vesicular gland of the African giant rat (Cricetomys
      gambianus, Waterhouse): histology and ultrastructure.
AB  - The epithelium of the vesicular gland of the African giant rat was studied by the
      light and electron microscopes. The gland is compound tubuloalveolar, lined by a
      columnar epithelium, the apical surface of which is covered by a few short
      microvilli. The epithelial cells are the principal and basal cells. The principal
      cells have an abundance of rough surfaced endoplasmic reticulum (rER), which are
      often arranged in whorls. Basal cells are few, being wedged between adjacent
      principal cells in the basal region. They are fairly electron lucent and contain
      fewer organelles. Intraepithelial lymphocytes, which also occur mostly in the
      basal region are also present in the epithelium. The presence of these latter
      cells is noteworthy in that they are not a known feature of the epithelium of the
      vesicular gland of other species.

PMID- 10895234
TI  - Serum calcium levels in patients with active pulmonary tuberculosis.
AB  - One hundred and two consecutively diagnosed pulmonary tuberculosis patients were
      recruited and followed up to ascertain the occurrence of hypercalcaemia before
      and during treatment with the modified short course antituberculosis therapy.
      Forty-five patients had hypocalcaemia at presentation, four of whom had
      hypoalbuminaemia. All those with hypocalcaemia had moderate to extensive
      radiographic disease on enrollment with BMI of less than 20. On commencement of
      treatment with the modified short course therapy, two of those with extensive
      cavitary radiographic disease developed transient asymptomatic hypercalcaemia.
      Although the hypoalbuminaemia and the hypocalcaemia seem to be related to the
      extent of radiographic disease and the poor nutritional status of the patients at
      presentation, no specific cause for the transient hypercalcaemia was found.

PMID- 10895236
TI  - Hypertension and primary myocardial disease in congestive cardiac failure.
AB  - This study has tried to use end diastolic diameter the index of chamber
      dilatation to discriminate between hypertensive heart failure and diluted
      cardiomyopathy as both conditions are known to overlap in cases of congestive
      cardiac failure. The sensitivity, specificity and positive predictive value was
      66.7%, 68% and 66.7% respectively. This means that alone, end diastolic diameter
      is not a very acute discriminator in cases where an overlap as shown in the
      figure occurs. It is therefore necessary to use all discriminatory indices in
      combination to get better accuracy.

PMID- 10895238
TI  - Analysis of the essential oil of Juniperus procera Endl. growing in Kenya.
AB  - The essential oil of the wood of Juniperus procera Endl. (Cupressaceae) from the
      Aberdares mountains, Central Province, Kenya has been extracted by steam
      distillation for varying times and analyzed using GC and GC-MS. The optimum time
      has been found to be 8 hours with the yield of the oil and cedrol as 0.48 and
      79.10%, respectively. Other constituents include 3,4-dimethylbiphenyl, a-cedrene,
      camphor, trans-geraniol, eugenol, and a-terpineol.

PMID- 10895237
TI  - The role of adrenergic receptors in the increased glucose uptake by the canine
      gut.
AB  - The study was carried out on fasted anaesthetized dogs. A vein draining a segment
      of the upper jejunum was cannulated for blood flow measurement. Arterial blood
      and venous blood from the upper jejunal segment, were obtained for measurement of
      glucose content. Glucose uptake was calculated as the product of jejunal blood
      flow and the difference between arterial and venous glucose levels. Prazosin,
      (0.2 mg/kg) had no effect on the glucose uptake induced by insulin and glucagon
      injections and glucose infusion. However, prazosin reduced the glucose uptake by
      about 50% during adrenaline-induced hyperglycaemia. Pretreatment of the animal
      with propranolol (0.5 mg/kg) significantly reduced the increased glucose uptake
      caused by adrenaline, glucagon and glucose hyperglycaemia. Propranolol also
      reduced by half the negative glucose uptake during insulin-hypoglycaemia. Since
      both the alpha and beta adrenergic receptor blocking agents did not abolish the
      induced glucose uptake, it was concluded that the effects of adrenaline,
      glucagon, glucose and insulin on intestinal glucose uptake are mediated in part
      by beta adrenergic receptors.

PMID- 10895239
TI  - Altered responses of isolated aortic smooth muscle following chronic ingestion of
      palm oil diets in rats.
AB  - The responsiveness of the rat aorta after chronic consumption of 15% (wt/wt)
      fresh and thermally oxidized palm oil diets was studied under standard organ bath
      procedures. Aortic rings from the oxidized oil-fed group showed significantly (P
      < 0.05) enhanced vascular responses to noradrenaline and potassium chloride when
      compared with the control and fresh palm oil-fed groups. The maximum tensions
      were 285.10 +/- 30 mg/mg tissue weight for the oxidized oil-fed group and 148.98
      +/- 36 mg/mg for the control in response to noradrenaline. The fresh oil-fed
      group produced maximum tension of 133.9 +/- 20 mg/mg which was not significantly
      different from the control. The trend was similar with potassium chloride. The
      maximum tensions were 206.31 +/- 25 mg/mg for the oxidized oil-fed group and
      93.33 +/- 13 mg/mg for the control group. The fresh oil-fed group produced
      maximum tension of 109.31 +/- 7.8 mg/mg which was not significantly different
      from the control. Relaxation to acetylcholine was significantly (P < 0.01)
      attenuated in the aortic rings obtained from the oxidized palm oil-fed group when
      compared with the control and fresh palm oil-fed groups. The percentage maximum
      relaxations to acetylcholine were 28.1 +/- 6.7% in the oxidized oil-fed group,
      71.4 +/- 6.0% in control and 78.2 +/- 6.0% in the fresh oil-fed groups. The
      relaxation in the fresh oil-fed group was not significantly different from
      control. These results suggest that functional changes occur in rat blood vessels
      after chronic consumption of thermally oxidized palm oil.

PMID- 10895240
TI  - Measurement of cell numbers by means of the endogenous enzyme hexosaminidase:
      applications to cell adhesion assays in endometrial and ovarian carcinoma cell
      lines.
AB  - Using a chromogenic substrate for the lysosomal enzyme, hexosaminidase to
      estimate cell numbers, a sensitive, simple, and non-radioactive procedure has
      been previously developed (1) in which microtiter reaction wells are directly
      scanned using a spectrophotometer. The applications of this method to
      quantitation of cell numbers and adhesion assays to coated substrates in
      endometrial adenocarcinoma (Ishikawa) and epithelial ovarian cancer (Ovcar) cells
      are discussed. The methods are safe, cheap, and easily applicable to biological
      researches particularly in developing countries.

PMID- 10895241
TI  - Perception of gingival bleeding by Nigerians.
AB  - Two hundred and seventy-five (275) subjects were seen to assess their perception
      of gingival bleeding and relate it to their periodontal status, sex, and age.
      Only about a quarter of the subjects claimed to bleed from the gingivae during
      routine oral prophylaxis. Unfortunately, about the same number admitted to having
      gum disease, whereas during clinical oral examination it was discovered that all
      these subjects had gingival bleeding. Also this study showed that more of the
      subjects who claimed to bleed from the gums thought it was normal compared to
      those who claimed not to bleed from the gums. The conclusion from the study is
      that there is poor perception of gingival bleeding and little relevance is placed
      on its presence in the mouth. There is poor awareness of it as a sign of the
      presence of pathology of the tooth supporting structures (periodontium), which
      may be due to local or systemic body disorders. The medical community must,
      therefore, recognize this fact and educate their patients and the public at
      large.

PMID- 10895242
TI  - Thyroid function in haemodialysed patients of Gassim, Saudi Arabia: TRH
      stimulation.
AB  - To study the hypophysical-pituitary-thyroid axis in Saudi patients on (RDT), 200
      units of TRH were given intravenously predialysis to each of 21 such subjects. As
      expected (TSH) rose promptly within 30 minutes followed by a gentle decline at 60
      minutes. A more gentle rise was also noted in T3 which continued for the 60
      minutes of observation. Rather unexpectedly, T4 level was noted to show a
      reciprocal decline. To our knowledge, this pattern has not been defined in
      literature. In 12 patients (GH) was noted to rise promptly within 30 minutes
      followed by a gentle decline at 60 minutes. (LH) and (FSH) did not follow any
      definite pattern as observed for T3 and T4. Since the oral preparation of TRH is
      now available, can (TRH) be effectively used to treat renal dwarfism?

PMID- 10895243
TI  - Acute encephalopathy associated with metronidazole therapy.
AB  - A forty-eight year-old male with amoebic liver abscess became encephalopathic 3
      days following oral metronidazole. Withdrawal of the drug led to prompt
      resolution of all encephalopathic symptoms.

PMID- 10895244
TI  - Cervicovaginitis emphysematosa mimicking carcinoma of the cervix: a case report.
AB  - Cervicovaginitis emphysematous is a rare self-limiting disease in which multiple
      gas-filled cysts are present in the submucosa of the upper vagina and ectocervix.
      We report a case in a 40 year-old trader who presented with clinical features
      suggestive of carcinoma of the cervix. It is hoped that this case report will
      heighten the awareness of clinicians and pathologists in the recognition of this
      unusual condition.

PMID- 10895245
TI  - Treatment of parkinsonian syndromes in developing countries.
AB  - Parkinsonism is the commonest extrapyramidal disorder. The condition arises when
      the striatonigral dopamine content falls below a critical value. The principle of
      treatment is dopamine replacement or counteracting the effects of acetycholine,
      the neurotransmitter which is in abundance. The choice of drug is determined by
      availability, cost, and side effects. The most commonly prescribed drugs in
      developing countries are the anticholinergics, which are the least expensive. The
      dopamine-replacement agents are second-line drugs and it appears as if low doses
      are effective in improving rigidity, gait abnormality, and postural instability.
      The use of dopa-agonist drugs is more limited, because of cost and side effects.
      Surgical management of cases is still in its infancy in developing countries.
      This review also highlights the more recent modes of management practised mainly
      in developed countries.

PMID- 10895246
TI  - Neuro-ophthalmological features of cerebral venous obstruction.

PMID- 10895247
TI  - Intersexuality and gender identity differentiation.

PMID- 10895248
TI  - The development of sexual orientation in women.

PMID- 10895249
TI  - Clinical ethnography and sexual culture.

PMID- 10895250
TI  - Revisiting the concept of sexual motivation.

PMID- 10895251
TI  - Central nervous system pathways involved in the control of penile erection.

PMID- 10895252
TI  - Sex, social institutions, and social structure: anthropological contributions to
      the study of sexuality.

PMID- 10895254
TI  - Evaluating sexual science: problems and prospects.

PMID- 10895253
TI  - The sexual pain disorders: is the pain sexual or is the sex painful?

PMID- 10895256
TI  - Kell, Kx and the McLeod syndrome.
AB  - The antigens of the Kell blood group system are carried on a 93 kDa type II
      glycoprotein encoded by a single gene on chromosome 7 at 7q33. XK is a 50.9 kDa
      protein that traverses the membrane ten times and derives from a single gene on
      the X chromosome at Xp21. A single disulphide bond, Kell Cys 72-XK Cys 347, links
      Kell to XK. The Kell component of the Kell/XK complex is important in transfusion
      medicine since it is a highly polymorphic protein, carrying over 23 different
      antigens, that can cause severe reactions if mismatched blood is transfused and
      in pregnant mothers antibodies to Kell may elicit serious fetal and neonatal
      anaemia. The different Kell phenotypes are all caused by base mutations leading
      to single amino acid substitutions. By contrast the XK component carries a single
      blood group antigen, termed Kx. The physiological functions of Kell and XK have
      not been fully elucidated but Kell is a zinc endopeptidase with endothelin-3
      converting enzyme activity and XK has the structural characteristics of a
      membrane transporter. Lack of Kx, the McLeod phenotype, is associated with red
      cell acanthocytosis, elevated levels of serum creatine phosphokinase and late
      onset forms of muscular and neurological defects.

PMID- 10895255
TI  - What do mouse gene knockouts tell us about the structure and function of the red
      cell membrane?
AB  - Recent development of knockout mice with targeted deletion of specific genes
      encoding various red cell membrane proteins has added valuable armamentarium to
      red cell membrane structure-function studies. In this chapter we will summarize
      the various recent developments regarding the structure and function of the red
      cell membrane derived from studies using knockout mice. In addition to being
      expressed in red cells, all major red cell membrane proteins are also expressed
      in cells of various tissues. The potential use of knockout mice to decipher the
      biological functions of red cell membrane proteins in non-erythroid cells is also
      explored.

PMID- 10895257
TI  - Erythroid band 3 variants and disease.
AB  - This review describes some of the naturally occurring band 3 (AEI) variants and
      their association with disease. Southeast Asian Ovalocytic (SAO) band 3, an
      inactive and misfolded protein, is probably only maintained in certain
      populations because it provides protection against the cerebral form of malaria.
      Many mutations that cause instability of band 3, either at the mRNA or protein
      level, result in hereditary spherocytosis (HS). Some polymorphisms alter amino
      acid residues in the extracellular loops of band 3 and are associated with blood
      group antigens. A truncated form of AEI is expressed in kidney cells and certain
      AEI mutations are associated with distal renal tubular acidosis (dRTA). The
      molecular basis of these variants and their effect on the structure and function
      of band 3 are discussed. The association between band 3 and glycophorin A (GPA)
      and the structure/function changes of band 3 in the absence of GPA are also
      described.

PMID- 10895258
TI  - RH blood group system and molecular basis of Rh-deficiency.
AB  - Rhesus (Rh) antigens are defined by a complex association of membrane
      polypeptides that are missing or severely deficient from the red cells of rare
      Rhnull individuals who suffer a clinical syndrome of varying severity
      characterized by abnormalities of the red cell shape, cation transport and
      membrane phospholipid organization. The Rhnull phenotype is an inherited
      condition that may arise from homozygosity either for a 'suppressor' gene
      unrelated to the RH locus ('regulator type') or for a silent allele at the RH
      locus itself ('amorph type'). A current model suggests that the proteins of the
      Rh complex (Rh, RhAG, CD47, LW, GPB) are assembled by non-covalent bonds and that
      it is not assembled or transported to the cell surface when one subunit is
      missing. Rh and RhAG proteins belong to the same protein family and are
      quantitatively the major components that form the core of the complex, which is
      firmly linked to the membrane skeleton. Molecular analysis of Rhnull individuals
      has revealed that abnormalities occur only at the RHAG and RH loci, without
      alteration of the genes encoding the accessory chains. Mutations of the RHAG
      gene, but not of RH, occur in all Rhnull individuals of the regulator type
      (including Rhmod) investigated so far (13 cases), strongly suggesting that RHAG
      mutants act as 'suppressors' and not as transcriptional regulators of the RH
      genes and that variable expression of the RHAG alleles may account for the Rhmod
      phenotypes (exhibiting weak expression of Rh antigens). Conversely, mutations of
      the RHCE gene, but not of RHAG, occur in two unrelated Rhnull individuals of the
      amorph type, supporting the view that RH mutants result from a 'silent' allele at
      the RH locus. These findings strongly support the Rh complex model since when
      either the Rh or RhAG protein is missing, the assembly and/or transport of the Rh
      complex is defective. Transcriptional as well as post-transcriptional mechanisms
      may account for the molecular abnormalities, but experimental evidence based on
      expression models is required to test these hypotheses, in the hope that they may
      help to clarify the biological role of the Rh proteins in the red cell membrane.

PMID- 10895259
TI  - The congenital dyserythropoietic anaemias.
AB  - Congenital dyserythropoietic anaemias (CDA) are a category of rare genetic
      diseases that affect erythropoiesis. Dyserythropoiesis is associated with
      abnormal erythroblasts and leads to altered red cells, the amount of which is
      insufficient. There are three main, well-defined CDAs, CDA I, II and III. Their
      characterization is based on a careful examination of the bone marrow under light
      and electron microscopes. In addition, a number of rare or unique forms of
      dyserythropoiesis have been reported. At least with respect to CDA I to III, the
      clinical evaluation is reaching an ever increasing refinement: age of discovery,
      determinants of iron overload and/or biliary complications. Over the past few
      years, a more promising breakthrough has been the localization of the genes
      responsible for CDA I, II and III, that is, 15q15.1-q15.3, 20q11.2 and 15q21-q25,
      respectively. Epidemiological studies have now become possible. The
      identification of the genes is pending.

PMID- 10895260
TI  - The hereditary stomatocytoses and allied disorders: congenital disorders of
      erythrocyte membrane permeability to Na and K.
AB  - The hereditary stomatocytoses and allied disorders are a set of dominantly
      inherited haemolytic anaemias in which the plasma membrane of the red cell
      'leaks' sodium and potassium. There are about 10 different forms of these
      conditions, ranging from a moderately severe haemolytic anaemia to minor
      conditions in which the haematology is essentially normal, but where the patients
      present with pseudohyperkalaemia, due to leakage of K from the red cells on
      cooling to room temperature. Frequently misdiagnosed as atypical hereditary
      spherocytosis, these conditions can show marked thrombotic complications after
      splenectomy, which should be avoided. Laboratory studies of these conditions have
      drawn attention to a 32 kDa membrane protein, stomatin, which seems to act as a
      regulator of Na and K transport in human and animal tissues generally, but
      mutations in this gene do not cause these diseases. Genetic mapping in some
      kindreds, but not all, points to a mutation locus on chromosome 16.

PMID- 10895261
TI  - Erythroid cell adhesion molecules Lutheran and LW in health and disease.
AB  - The Lutheran and LW glycoproteins are blood group-active proteins found at the
      surface of human red cells. The Lutheran glycoprotein (Lu gp) is a member of the
      immunoglobulin superfamily (IgSF) that binds the extracellular matrix protein
      laminin, in particular, laminin isoforms containing the alpha 5 subunit. The LW
      glycoprotein (LW gp), also an IgSF member, has substantial sequence homology with
      the family of intercellular adhesion molecules (ICAMs). LW gp binds the integrin
      very late antigen-4 (VLA-4, alpha 4 beta 1) and alpha V-containing integrins.
      Studies on the expression of LW and Lu gps during erythropoiesis utilizing in
      vitro cultures of haemopoietic progenitor cells have shown that LW gp expression
      precedes that of Lu gp. These observations have led to the suggestion that LW gp
      on erythroblasts may interact with VLA-4 on macrophages to stabilize
      erythroblastic islands in normal bone marrow and that Lu gp may facilitate
      trafficking of more mature erythroid cells to the sinusoidal endothelium where
      alpha 5-containing laminins are known to be expressed. Levels of Lu gp and LW gp
      expression on sickle red cells are greater than on normal red cells and sickle
      red cells adhere to alpha 5-containing laminins. These data suggest that the Lu
      and LW molecules may contribute to the vaso-occlusive events associated with
      episodes of acute pain in sickle cell disease.

PMID- 10895262
TI  - Adhesive receptors on malaria-parasitized red cells.
AB  - Antigenic variation, rosetting and cytoadhesion are key determinants in the
      survival and virulence of the malaria parasite Plasmodium falciparum. These
      properties reside in a multigene protein family called P. falciparum erythrocyte
      membrane protein I (PfEMPI), encoded by the large and diverse var gene family.
      PfEMPI plays a central role in the biology of P. falciparum and its interaction
      with the human host. The molecular mechanism and the domains involved in
      cytoadherence, rosetting and antigenic variation are beginning to unfold. Domains
      mediating rosetting and adhesion to several key host receptors have already been
      identified. Understanding the role of PfEMPI in the pathogenesis and survival of
      malaria parasites is the key for the development of anti-adhesion vaccines and
      therapeutics to reduce the mortality and morbidity of P. falciparum infections.

PMID- 10895263
TI  - Human genome project: implications for medical science.

PMID- 10895264
TI  - An effective and affordable cervical carcinoma screening programme for Sri Lanka.

PMID- 10895265
TI  - Genital warts.

PMID- 10895266
TI  - Developing a molecular marker for metachronous colorectal cancer.
AB  - OBJECTIVE: To determine the prevalence of microsatellite instability in patients
      with metachronous colorectal cancer as a potential marker for identification of
      high risk individuals. SETTING: Surgical research laboratory, Whittington
      Hospital, Highgate Hill, London. SUBJECTS AND METHODS: 37 colorectal tumours from
      18 individuals with metachronous colorectal cancers were investigated at five
      microsatellite loci by single stranded conformational polymorphism (SSCP)
      analysis. A control group of 11 individuals who had developed one sporadic
      colorectal cancer each were also similarly analysed. MEASUREMENTS: Tumour
      microsatellite instability was defined as the appearance of new polymarase chain
      reaction (PCR) bands, either larger or smaller than those produced from the
      normal mucosa. RESULTS: 27 of the total of 37 metachronous cancer specimens PCR
      amplified successfully. Microsatellite instability was demonstrated in 59.3%
      (16/27) of individuals with metachronous tumours. None of the tumours in the
      control group showed microsatellite instability. CONCLUSIONS: These results
      suggest that individuals with colorectal cancer with replication errors are at a
      greater risk of developing metachronous colorectal cancer than those without
      replication errors.

PMID- 10895267
TI  - Thyroid function in thalassaemia major.
AB  - INTRODUCTION: Short stature is common in thalassaemia major. Hypothyroidism
      resulting from haemosiderosis has been implicated, but this complication has not
      been investigated in Sri Lanka. OBJECTIVES: To estimate the thyroid hormone level
      of patients with thalassaemia major and correlate height with age, iron status
      and thyroid hormone level. SETTING: University Unit, Lady Ridgeway Hospital,
      Colombo. DESIGN: A cross-sectional comparative study. METHODS: 33 patients with
      thalassemia major (19 males) aged 2 years 6 months to 23 years were studied. 21
      healthy age and sex matched subjects from the same neighbourhood as the patients
      served as controls. Anthropometric measurements, skeletal maturity, serum
      ferritin and thyroid hormone levels were estimated. RESULTS: The height centiles
      and height standard deviation scores (SDS) were significantly lower in the
      patient group. Skeletal maturation was delayed by more than 1 year in 69% of
      patients. Undernutrition was not seen. The height SDS showed significant
      reduction with age (r = -0.5, 95% confidence limit -0.72 to -0.18) and with
      elevated serum ferritin levels (r = -0.8, 95% confidence limit = -0.9 to 0.62).
      Serum ferritin levels were elevated in the entire patient group with 70% being
      heavily iron overloaded (serum ferritin > 7000 ng/ml). The thyroxine (T4) levels
      were within the normal range in all 33 patients. The TSH levels were normal in 32
      patients. The patient too had a normal T4 level. The control group had TSH levels
      comparable with the patients. CONCLUSION: Hypothyroidism was not present in our
      iron overloaded thalassaemic patients. The thyroid hormone levels were similar in
      patients with mild and heavy iron overload. We conclude that routine surveillance
      for hypothyroidism is unnecessary in thalassaemia major. Other causes for delayed
      skeletal maturation and short stature need investigation.

PMID- 10895268
TI  - Severe systemic effects of Merrem's hump-nosed viper bite.
AB  - OBJECTIVE: To report unpredictable severe systemic effects of hump-nosed viper
      envenomation. SETTING: Medical unit, General hospital, Anuradhapura. METHODS: The
      clinical outcome of seven patients bitten by Merrem's hump-nosed viper were
      monitored until recovery or death. Limited autopsies were performed on the
      latter. Offending snakes were positively identified by medical officers and in
      one instance by a herpetologist. CONCLUSION: Merrem's hump-nosed viper bites,
      caused an array of potentially fatal systemic manifestations. One patient
      developed neurological effects, severe Raynaud's syndrome leading to ascending
      gangrene of distal limbs and adult repiratory distress syndrome (ARDS), in
      addition to the known complications of severe renal cortical necrosis and
      haemostatic dysfunction. Two patients who developed acute renal failure and
      prolonged coagulopathy recovered completely. The combination of extensive renal
      cortical necrosis, disseminated intravascular coagulation, and ARDS proved fatal
      in three.

PMID- 10895269
TI  - A case of eosinophilic meningitis.
AB  - A case of eosinophilic meningitis is reported, a condition not previously
      reported from Sri Lanka. We propose Angiostrongylus cantonesis to be the most
      likely causative agent in this patient.

PMID- 10895270
TI  - Kimura's disease in a Sri Lankan man.

PMID- 10895271
TI  - Neonatal herpes zoster infection.

PMID- 10895272
TI  - Cigarette smoking and anaesthesia.

PMID- 10895273
TI  - Heat stroke in young adults.

PMID- 10895274
TI  - All that glitters in glitazones.

PMID- 10895275
TI  - Re-emergence of measles.

PMID- 10895276
TI  - Antipersonnel mines--a continuing threat to Sri Lankans in the new century.

PMID- 10895277
TI  - Intestinal helminth infections among children in a slum community in Enderamulla.

PMID- 10895278
TI  - Methyldopa use should be restricted.

PMID- 10895279
TI  - A sailor with a bubo.

PMID- 10895280
TI  - Successful desensitisation of allopurinol-induced erythema multiforme.

PMID- 10895281
TI  - Prostatic carcinoma in Sri Lanka--is it more common than cancer registry
      statistics?

PMID- 10895282
TI  - [The effect of obesity on ovarian function. I. Serum insulin and insulin
      dependent protein concentrations in obese patients with polycystic ovary
      syndrome].
AB  - OBJECTIVES: The aim of the present study was to estimate the role of insulin in
      the pathogenesis of polycystic ovary syndrome. DESIGN: The study was carried out
      in 21 obese women with PCO, 18 obese women without menstrual disturbances and 9
      normal-weight healthy women. MATERIALS AND METHODS: In all patients
      antropomethric parameters: weight, height, % of body fat, waist and hip girths
      were measured and than BMI and WHR were calculated. Oral glucose tolerance test
      after 75 g glucose was done after overnight fast. Plasma glucose and insulin were
      measured in 0 min, 60 min and 120 min of the test. The concentrations of IGF-I,
      IGFBP-1, SHBG, LH, FSH, testosterone, cortisol, PRL, estradiol, were estimated.
      RESULTS: There was statistical significant difference between plasma insulin
      concentrations in obese patients with PCO in comparison to obese women with
      normal menstrual cycle (p < 0.05) and control group (p < 0.001). The
      concentrations of IGFBP-1 and SHBG were similar in both groups of obese patients
      and differ markedly in comparison to the control group. There were significant
      correlation between plasma insulin and % body fat, BMI and waist girth in all
      studied groups. CONCLUSIONS: We conclude that in obese women with PCO insulin
      influence ovarian androgen production and decreases the serum SHBG and IGFBP-1
      which could contribute in the augmentation of the symptoms of PCO.

PMID- 10895283
TI  - [The influence of obesity on ovarian function. II. Plasma leptin concentration in
      women with polycystic ovary syndrome].
AB  - OBJECTIVES: The aim of the present study was to estimate the leptin role in the
      pathogenesis of polycystic ovary syndrome. DESIGN: The study was carried out in
      21 obese women with PCO, 18 obese women without menstrual disturbances and 9
      normal-weight healthy women. MATERIALS AND METHODS: In all patients
      antropomethric parameters: weight, height, % of body fat, waist and hip girths
      were measured and than BMI and WHR were calculated. Plasma concentrations of
      leptin, insulin, LH, FSH, testosterone, cortisol, PRL, estradiol were estimated.
      RESULTS: There were no statistical significant difference between plasma leptin
      concentrations in obese patients with PCO in comparison to obese women with
      normal menstrual cycle. In both groups of obese patients plasma leptin
      concentrations was significantly higher than in control group (p < 0.001, p <
      0.001). There were significant correlation between plasma leptin and % body fat,
      BMI and waist girth in all studied groups. CONCLUSIONS: We conclude that leptin
      is not directly involved in observed hormonal disturbances in polycystic ovary
      syndrome. The main predictor of plasma leptin concentrations in patients with PCO
      is amount of body fat.

PMID- 10895284
TI  - [May GM-CSF influence the ability to fertilize oocytes?].
AB  - The aim of this work was to evaluate the concentration of granulocyte-macrophage
      colony stimulating factor (GM-CSF), IL-1 beta IL-6 and TNF alpha in follicular
      fluid obtained from mature oocytes during in vitro fertilization scheme and to
      determine a correlation between GM-CSF concentration and the analyzed cytokines.
      Material consisted of 36 samples of follicular fluid which were divided into two
      groups: the first one--17 samples of follicular fluid obtained from follicles
      with successful oocyte fertilization and cleavage and the second one--19 samples
      of follicular fluid with unsuccessful fertilization. The concentration of GM-CSF
      as well as IL-6, IL-1 beta and TNF alpha in follicular fluid was evaluated by
      using the ELISA immunosorbent assays. The mean concentration of GM-CSF, IL-6, IL
      1 beta was similar in both groups, however, the frequency of occurrence of these
      parameters as well as coexistence of GM-CSF with analyzed cytokines were higher
      in the second group i.e. in the follicular fluid with unsuccessful fertilization.
      We found a positive correlation between concentration of GM-CSF and IL-6 in
      follicular fluid of all samples. The authors suggested that activation of
      macrophages to an increased release of GM-CSF during disturbance of oocyte's
      maturation might implicate a relation between immune and endocrine systems with
      cytokine mediation.

PMID- 10895285
TI  - [Analysis of the frequency of prevalence of endometrial hyperplasia and
      endometrial adenocarcinoma based on own material in the year 1975, 1985 and
      1995].
AB  - We analysed the frequency of prevalence of endometrial hyperplasia and
      endometrial adenocarcinoma in the years 1975, 1985 and 1995. Significant
      differences between endometrial simple hyperplasia and complex hyperplasia with
      atypia was found. There were no statistic differences in the frequency of the
      prevalence of endometrial adenocarcinoma between analysed years.

PMID- 10895286
TI  - [Evaluation of using Levovist in the differential diagnosis of ovarian tumors].
AB  - The research on applying Levovist was carried out in the Department of Obstetrics
      and Gynaecology of Medical Academy in Bydgoszcz, Poland, in the years 1997-1998.
      Out of 118 hospitalised patients with preliminary diagnosis: tu. hypogastrii, tu.
      adnexorum, tu. ovarii, cystis ovari, due to the suspicious ultrasound result,
      and/or decreased parameters of arterial blood flow (PI < 1.0; RI < 0.6) and or
      presence of abdominal fluid, 32 women were included in the study. The changes in
      the Doppler image under the influence of Levovist and their correlation with
      histologic features were analysed. The time span between injection of Levovist
      and the enhancement of the Doppler image was not characteristic for any tumor.
      However, it was observed, that the mean return time i.e. from the enhancement of
      the Doppler signal to the initial pattern, was considerably longer in carcinomas
      than in other ovarian tumours. No signal enhancement was observed in benign
      lesions.

PMID- 10895287
TI  - [Omental cyst imitating tumor of ovary: case report].
AB  - Omental cyst is a rare lesion occurring primarily during childhood and young
      adulthood. The rarity of these lesions, with an incidence of only about 1 in
      105,000 to 1 in 140,000 hospital admissions, and the absence of characteristic
      clinical findings makes diagnosis difficult. The authors describe a case of an
      omental cyst in woman aged 49 years which became directed to Department of
      Gynecology & Obstetric in Hospital of Slupsk on account suspicions of ovarian
      tumor. The diagnosis of omental cyst and subserosum uterine myoma was done after
      ultrasonographic examination. The laparotomy was performed: the excision of
      omental cyst and uterine fibrome was done. The histological examination confirmed
      the macroscopic observations. The post-operative period was uneventful.

PMID- 10895288
TI  - [Normal pregnancy after laser salpingostomy, blighted ovum, and right tubal
      pregnancy treated with methotrexate].
AB  - The 8-years lasting primary infertility in 28 years old woman was caused by
      bilateral hydrosalpinx, anovulation and husband's oligozoospermia. CO2 laser
      salpingostomy, treatment of the husband and ovulation induction with clomiphene
      citrate were successful. The consecutive pregnancies were achieved: 1. blighted
      ovum, 2. right tubal pregnancy cured with (MTX), 3. normal pregnancy.

PMID- 10895289
TI  - [Pathophysiological aspects of adipose tissue development in women].
AB  - The fat cell, the functional entity of adipose tissue, is mainly involved in
      energy storage and mobilization. The deposition of fat in, and the mobilization
      of fat from, adipose tissue are precisely controlled by enzyme activities: LPL
      and HSL. These functions are under control of hormones such as insulin,
      catecholamines and, to some extent, steroid hormones. The adipocytes have been
      recently identified as the source of many factors that may act like hormones
      either in the local environment or at distant sites, are also target cells for
      many more hormones. Adipose tissue metabolism varies from one region of the body
      to another. The metabolic activity is the lowest in the subcutaneous
      gluteofemoral area, followed by the abdominal subcutaneous area, and the highest
      in the visceral region. The metabolic activity of gluteofemoral fat is activated
      in lactating mothers. Body fat content changes with female age. Puberty, parity
      and menopause seems to increase accretion of adipose tissue. Obesity is defined
      as an increase in body fat content. There is general agreement that obesity
      develops as an interaction between a genetic susceptibility and environment which
      is expressed when the subject is exposed to a certain set of environmental
      conditions. Obesity develops when energy intake exceeds energy expenditure over a
      prolonged period. Excess body weight is associated with several diseases which
      can shorten life expectancy. The prevalence of obesity is high and increases
      steadily. Approximately 20-40% of women are overweight (BMI 25-30 kg/m-2) and 5
      20% are obese (BMI > 30 kg/m-2).

PMID- 10895290
TI  - [Obesity as an obstetric risk factor].
AB  - Obesity-related metabolic and functional disorders may disturb adaptation process
      taking place in pregnant women body. Insufficient adaptation may lead to
      development of several medical complications during pregnancy, labor, delivery,
      and puerperium. Maternal obesity is associated with increased frequencies of
      hypertension, preeclampsia, gestational diabetes mellitus, fetal macrosomia,
      congenital malformations, labor abnormalities (including prolonged second stage
      of labor, meconium-stained amniotic fluid, FHR abnormalities and shoulder
      dystocia), postdatism, and cesarean delivery. Operative complications among obese
      women undergoing cesarean delivery include increased blood loss, prolonged
      operative time, and increased rates of postoperative infection, thrombophlebitis.
      Treatment of these complications increases hospital stays and costs. Obese women
      should be carefully examined by dietetician before conception and cared for
      dietetically and medically during gestation.

PMID- 10895292
TI  - [Immunohistochemically expression of the protein p53 evaluated in invasive
      squamous cell carcinoma of the cervix].
AB  - The p53 protein expression in the invasive squamous cell carcinoma of the cervix
      was evaluated immunohistochemically. Its predictive role in the correlation with
      histological grading and staging was analyzed. 13.7% of examined cases (10/73)
      presented positive protein expression. There was no correlation between the
      intensified protein p53 expression and particular prognostic histological
      factors.

PMID- 10895291
TI  - [Beta subunit of human chorionic gonadotropin, CA 125 antigen and CA 19-9 antigen
      with non-trophoblastic malignancy of genital tract. Vulval cancer].
AB  - Our investigations embraced the group of patients with vulval cancer before
      surgical treatment (n = 10). We measured in serum of blood the level of the total
      human chorionic gonadotrophin hCG, beta subunit of human Chorionic Gonadotrophin,
      CA 125 and CA 19-9 antigen. We ascertained significant elevation the beta subunit
      of hCG level in the group of women with neoplasms in comparison with control
      group (n = 96) and significant positive correlation between beta subunit level
      and degree of cancer cells maturity (r = 0.66, p < 0.05). We also ascertained
      strong positive correlation among beta subunit of hCG and CA 19-9 antigen level
      in the serum of the patients with vulval cancer (r = 0.55 and p < 0.05).

PMID- 10895293
TI  - [The influence of selected prognostic factors on the results of combined
      treatment of invasive carcinoma of the cervix on stage IB and stage IIA].
AB  - This is a retrospective analysis of 180 patients treated by combination of
      radical surgery and radiotherapy for invasive carcinoma of the cervix in stage IB
      and IIA. The influence of the following prognostic factors on the survival has
      been evaluated: the presence of pelvic lymph node metastases, histopathology of
      the tumor, the size of the primary tumor, presence of vascular space invasion and
      surgical margines. Nodal status has proved to be the most important prognostic
      factor: 91% of patients without pelvic lymph node metastases survived 5 years,
      57% with up to two metastases and 36% with three and more metastases to the
      pelvic nodes. A significantly worse prognosis has also been observed in patients
      with adenocarcinoma of the cervix, and with the size of the tumor of more than 2
      cm.

PMID- 10895294
TI  - [Changes in arylsulphatase activity (EC 3.6.1) in the blood serum and urine in
      women during the pregnancy and in the course of delivery].
AB  - By the determination of arylsulphatase A activity (EC 3.1.6.1) in the blood serum
      and urine obtained from 66 women using the modified method by Lee-Vaupel and
      Conzelmann it was noticed the increase in the enzyme activity during the
      pregnancy comparing to the non-pregnant group. The highest enzyme activity was
      observed in the III trimester of pregnancy. In the following stages of delivery
      (I, II, III) it was assumed the increase in enzyme activity in urine. The highest
      enzyme activity in urine was observed in the stage III, and in the serum--in the
      stage II. It was compared the enzyme activity in primiparae and multiparae
      proving, that in the serum nd urine this activity is higher in the stages I and
      II in multiparae, and in the stage III in primiparae.

PMID- 10895295
TI  - [The arylsulphatase A (EC 3.1.6.1) activity in serum, urine and amniotic fluid
      from pregnant women with EPH-gestosis].
AB  - In serum, urine and amniotic fluid obtained from the 52. women divided into three
      groups the arylsulphatase A (EC 3.1.6.1) activity was measured by the modified
      Lee-Vaupel and Conzelmann method. It was noticed in serum from the pregnant women
      with EPH-gestosis the statistically significant (p < 0.05) increase in the enzyme
      activity comparing to the results from non-pregnant women and pregnant with
      normal course of pregnancy. It was no statistically significant differences in
      the urine from pregnant with EPH-gestosis and from the healthy pregnant, but
      there was the increase (p < 0.01) in the enzyme activity in amniotic fluid from
      pregnant women with EPH-gestosis comparing to the physiological course of
      pregnancy. According to our data, the arylsulphatase A activity assay could be
      recommended as a diagnostic marker in the EPH-gestosis.

PMID- 10895296
TI  - [Hypoglycemia in newborn of the diabetic mother in relation to some indicators of
      perinatal hypoxia].
AB  - DESIGN: To examine whether perinatal hypoxia increases the risk of occurrence of
      hypoglycaemia--between first and second hour of life--in newborn of the diabetic
      mother. MATERIAL AND METHODS: The study material consisted of 151 newborns born
      to 58 pregestational and 93 gestational diabetes mothers. The occurrence of
      hypoglycaemia was examined in accordance with some perinatal hypoxia indicators
      such as: 1 and 5 minutes Apgar scores, umbilical arterial blood gas analysis and
      cord blood erythropoietin (EPO) level. RESULTS: Newborns of the diabetic mothers
      in whom hypoglycaemia was recognised had lower 1 minutes Apgar scores, lower pH
      values, higher pCO2 values and higher EPO levels than those, in whom
      normoglycaemia was recognised. CONCLUSIONS: Low 1 minutes Apgar scores and
      occurrence of even mild perinatal hypoxia are factors increasing the risk of
      hypoglycaemia in the group of newborns of the diabetic mothers in the time
      between first and second hour of life.

PMID- 10895297
TI  - [Use of computer-assisted monitoring of twin pregnancy: a case report].
AB  - The authors present the use of computer-aided monitoring of pregnancy in case of
      twins. The computer program predicts date of delivery, birth weight and fetal
      maturity for single fetus pregnancy, however this values are in twins overstated.
      A valuable short time prediction are actual weight and biological age of each
      twin.

PMID- 10895298
TI  - [Vascular endothelium in pathogenesis of hypertension assosiated with pregnancy].
AB  - The role of vascular endothelial cell dysfunction and damage in pathogenesis of
      preeclampsia have been discussed in this paper.

PMID- 10895299
TI  - [Deontological aspects of ovarian stimulation].
AB  - The physician and the infertile couple should be partners in the development of a
      treatment plan that optimally meets the couple's needs. The information about the
      benefits, side effects and costs of treatment is to be presented to the couple.
      Stimulation of the ovary has become the central component of rapidly developing
      assisted reproduction. The fundamental rule in ovulation induction is individual
      approach to each patient and close monitoring of the stimulation, because the
      dangers of ovarian hyperstimulation syndrome, multiple pregnancy and putative
      longer term risks. There is general agreement that multiple pregnancies,
      including twins, are still too common and must be avoided as they are the major
      causes of maternal and fetal morbidity. Since the advent of ICSI tens of oocytes
      are not necessary to achieve fertilization, and milder forms of ovarian
      stimulation should suffice in most IVF/ICSI cycles. Our target in infertility
      treatment should be the birth of healthy, singleton babies, with no health risks
      to their mothers.

PMID- 10895301
TI  - WHO in partnership. Examples of work with the public and private sectors to fight
      infectious diseases.

PMID- 10895300
TI  - Progress towards poliomyelitis eradication, Nepal, 1996-1999.

PMID- 10895302
TI  - Biological phenotype and coreceptor usage of human immunodeficiency virus (a
      short review).

PMID- 10895303
TI  - The influence of chromium compounds on yeast physiology (a review).

PMID- 10895304
TI  - High pressure processing of foods for microbiological safety and quality (a short
      review).
AB  - Consumers are demanding foods that are "natural", of good nutritional and sensory
      quality, free from chemical preservatives, microbiologically safe and with
      extended shelf-life. High pressure processing can, potentially, meet these
      criteria. Recent advances in equipment design now allow foods to be processed up
      to 900 MegaPascals (130,000 psi). However, further work is required to more fully
      understand the factors that can affect the response of microorganisms, including
      pathogens, to pressure so that treatments can be optimised and microbiological
      safety can be assured. This paper describes how the pressure resistance of
      microorganisms can vary depending on factors such as species, strain, stage of
      growth and food composition. Strategies for overcoming the problem of pressure
      resistance will be discussed, for example the use of pressure cycling and the
      combination of pressure with mild heat. The current commercial uses of high
      pressure to preserve foods will be reported and potential applications will also
      be discussed.

PMID- 10895305
TI  - Genetic distinctness of African, Asian and South American local chickens.
AB  - The genetic variability of various local chicken populations derived from
      Bolivia, India, Nigeria and Tanzania was evaluated with 22 microsatellites.
      Between two and 11 alleles per locus were detected. All populations showed high
      levels of heterozygosity with the lowest value of 45% for the population named
      Aseel from India and the highest value of 67% for Arusha from Tanzania. A
      dendrogram was constructed based on CHORD distance by upgMa analysis. Within this
      tree the populations were assorted according to their geographical origin.
      Bootstrapping values within the dendrogram were between 37 and 99%. The
      contribution of the determination of genetic variability with genetic markers to
      the decision on conservation and/or further use of the populations in
      crossbreeding programs designed to create genetic stocks with improved
      adaptability and productivity in tropical countries is discussed.

PMID- 10895307
TI  - Linkage mapping and comparative analysis of bovine expressed sequence tags
      (ESTs).
AB  - Bovine expressed sequence tags (ESTs) containing microsatellites are suitable
      markers for both linkage and comparative maps. We isolated clones from a bovine
      fetal thigh skeletal muscle cDNA library that were positive for a (CA)10 probe.
      Thirty individual clones were isolated and characterised by sequencing. Sequences
      from the 5' and 3' ends of a clone were considered as separate ESTs until a
      contiguous sequence was identified. A total of 47 ESTs were sequenced from the 5'
      and/or 3' ends and full sequence was obtained for the 30 clones. BLAST nucleotide
      analysis identified significant homology to known mammalian coding regions for 31
      of the bovine ESTs, 30 of which also matched human ESTs or sequence-tagged sites
      (STS). The remaining 16 bovine ESTs represented novel transcripts.
      Microsatellites were isolated in 27 of the ESTs, 11 of which were developed into
      markers and placed on the MARC bovine linkage map. Human cytogenetic map
      positions were available for 20 of the 30 human EST orthologs, and a putative
      bovine map position for 17 of the sequences could be inferred using comparative
      mapping data. These results demonstrated that mapping bovine ESTs containing
      microsatellites is a plausible strategy to increase the density of gene markers
      on the bovine linkage and comparative maps.

PMID- 10895306
TI  - Characterisation of gene expression in bovine adipose tissue before and after
      fattening.
AB  - It has been reported that fattening causes bovine adipose tissue development
      associated with an enlargement in adipocyte cell size. As a first study to
      elucidate mechanisms of bovine adipose tissue development during fattening, our
      experiment was designed to characterise gene expression in bovine adipose tissue
      before and after fattening. We randomly isolated a large number of cDNA clones
      derived from bovine adipose tissue before and after fattening. Sequence analysis
      of the isolated clones showed that 3 and 10 clones from before and after
      fattening, respectively, correspond to genes related to adipocyte development
      and/or function in the adipose tissue. In addition, we isolated cDNA clones that
      possess negative signal by hybridising the cDNA population from the adipose
      tissue after fattening with that before fattening as a probe. As a result, we
      identified five types of transcripts observed in the adipose tissue after
      fattening but not before fattening. Two of the five are likely to encode bovine
      orthologs of phospholipase A2 and RNA helicase p68, while the other three
      represent unknown genes. Further functional investigation of the identified genes
      might lead to elucidation of mechanisms of bovine adipose tissue development
      during fattening.

PMID- 10895308
TI  - Phylogenetic analysis of the tribe Bovini using microsatellites.
AB  - The objective of the present study was to determine if the generally accepted
      phylogenetic relationships in the tribe Bovini correspond to a phylogenetic
      scheme derived from polymorphisms at 20 bovine microsatellite loci. This study
      comprises 17 representative populations: eight Bos taurus, two Bos indicus, one
      Poephagus, one Bibos, one Bison, three Bubalus and one Syncerus. Phylogenetic
      analyses using (delta mu)2 and chord (DC) distances revealed substantial
      divergence among species. Neighbor-joining trees with both distance measures
      showed only minor differences. Bos taurus and Bos indicus grouped first, followed
      by Bos frontalis (Mithan) and Bos grunniens (Yak), Bison bison branched off next
      and Bubalus bubalis and Syncerus caffer emerged as the two most divergent species
      from the Bos clade. These findings would suggest that Bos, Poephagus, and Bibos
      should be integrated into the Bos genus with each group classified as a subgenus.
      On the other hand, Bison, Bubalus and Syncerus should each be considered a
      separate genus. Direct estimates of the divergence times were calculated using
      the (delta mu)2 genetic distance. Bos taurus and Bos indicus were estimated to
      have diverged 0.31-0.82 MYA, Bos and Poephagus: 0.57-1.53 MYA, Bos and Bibos:
      0.57-1.52 MYA, Bos and Bison: 0.46-1.23 MYA, Bos and Bubalus: 1.85-4.93 MYA and
      Bos and Syncerus: 0.98-2.61 MYA.

PMID- 10895309
TI  - Mapping quantitative trait loci for stress induced alterations in porcine
      leukocyte numbers and functions.
AB  - To identify quantitative trait loci (QTLs) with effects on 'stress' induced
      alterations of porcine immune functions, a number of immune capacity traits were
      analysed in the F2 generation of a Wild Boar--Yorkshire intercross. All traits
      were measured prior, and one day after, exposure to experimental 'stress' (mixing
      and transport). The 'stress' protocol induced a decrease in numbers of
      circulating neutrophils and in spontaneous proliferation in vitro, whereas
      phagocytic capacity, mitogen induced proliferation and spontaneous IL-2 activity
      increased. The IFN-alpha production tended to decrease, although the individual
      variation was pronounced. More than 200 genetic markers have been scored in the
      entire pedigree and were used to trace the inheritance of individual chromosome
      segments. Wild Boar alleles were on average associated with higher mitogen
      induced IL-2 activity and a slightly lower decrease in IFN-alpha production after
      mixing and transport. Four QTLs with significant effects were identified; one
      influencing 'stress' induced alteration in numbers of neutrophils (chromosome 8),
      one influencing spontaneous proliferation after 'stress' (chromosome 2), one
      influencing mitogen induced IL-2 activity after 'stress' (chromosome 6) and one
      influencing 'stress' induced alterations in mitogen induced IL-2 activity
      (chromosome 12). In addition, several suggestive QTLs were indicated.

PMID- 10895310
TI  - Identification of a premature stop codon in the melanocyte-stimulating hormone
      receptor gene (MC1R) in Labrador and Golden retrievers with yellow coat colour.
AB  - We have examined whether black/yellow coat colour in Labrador retrievers is
      controlled by allelic variants at the extension locus. As the gene encoding the
      melanocyte-stimulating hormone receptor (MC1R) has been shown to correspond to
      the extension locus in several species, we have determined the genomic MC1R
      sequence in Labrador retrievers with black and with yellow coat colour. Using
      primers based on the fox (Vulpes vulpes) MC1R sequence we initially isolated and
      sequenced the innerpart of the canine MC1R. By means of inverse PCR we succeeded
      in the characterization of both flanking regions of the MC1R gene (Genbank:
      AF064455). Comparison of the complete MC1R sequences of a yellow and a black
      Labrador retriever revealed a single C-->T mutation at nucleotide position 916 in
      the yellow dog. This transition changed the codon for arginine at position 305
      into a stop codon, resulting in the elimination of the evolutionary strongly
      conserved 10 carboxyterminal amino acid residues. With an allele-specific
      oligonucleotide (ASO) test it was shown that the mutation cosegregated with the
      recessively inherited yellow coat colour in the Labrador retriever. Golden
      retrievers also appeared to be homozygous for the mutation. Seventeen other
      breeds were all negative for the mutation. Since the Labrador and Golden
      retriever are closely related, we suggest a common founder for the yellow coat
      colour in Labrador and Golden retrievers.

PMID- 10895311
TI  - Evolution of the ovine MHC DQA region.
AB  - Southern hybridisation was used to define an apparent gene duplication event at
      the ovine DQA2 locus. Approximately 500 sheep from five different breeds were
      genotyped at their DQA1 and DQA2 loci. A subset of these were selected for
      further characterisation. Southern hybridisation of TaqI digested DNA revealed no
      DQA1 region in some sheep. It was also noted in these DQA1 null animals the DQA2
      specific probe hybridised to two bands. An EcoRV-RFLP designed to distinguish
      copy number confirmed this duplication of the DQA2 region. The results showed
      that the duplication was exclusively associated with the DQA1 null haplotype and
      occurred only in alleles DQA2-F, -G, -I and -J. Comparison with bovine MHC genes
      revealed that they also contained a DQA1 null haplotype and that this haplotype
      was associated with a putative DQA3 gene. The potential for an ovine DQA3 locus
      is discussed.

PMID- 10895312
TI  - Consensus and comprehensive linkage maps of bovine chromosome 7.
AB  - The objective of this project was to integrate the currently available linkage
      maps for bovine chromosome 7 (BTA7) by combining data sets from eight research
      groups. A total of 54 unique markers were typed in eight pedigrees. Multilocus
      linkage analysis with CRI-MAP produced a bovine chromosome 7 consensus framework
      map of 27 loci ordered with odds greater than 1000:1. Furthermore, we present a
      bovine chromosome 7 comprehensive map integrating 54 loci. The locus order is in
      general agreement with the recently published linkage maps except for one
      discrepancy. The order of loci BM9289, BMS713, and ILSTS001 was reversed in the
      consensus framework map relative to the published USDA-MARC bovine chromosome 7
      linkage map.

PMID- 10895314
TI  - Microsatellite marker based genetic linkage maps of Oreochromis aureus and O.
      niloticus (Cichlidae): extensive linkage group segment homologies revealed.
AB  - Partial genetic linkage maps, based on microsatellite markers, were constructed
      for two tilapia species, Oreochromis aureus and Oreochromis niloticus using an
      interspecific backcross population. The linkage map for O. aureus comprised 28
      markers on 10 linkage groups and covered 212.8 CM. Nine markers were mapped to
      four linkage groups on an O. niloticus female linkage map covering 40.6 CM.
      Results revealed a high degree of conservation of synteny between the linkage
      groups defined in O. aureus and the previously published genetic linkage map of
      O. niloticus.

PMID- 10895313
TI  - Geographic and breed distribution of an Msp I PCR-RFLP in the bovine growth
      hormone (bGH) gene.
AB  - Information is presented on the frequency of the Msp I (-) allele in the third
      intron of the bovine growth hormone gene in a large number of cattle breeds.
      Consideration of the breed frequencies in relation to their geographic origin
      shows a low frequency for breeds originating in Northern Europe, moderate
      frequencies for breeds originating in Eastern Europe or the countries surrounding
      the Mediterranean basin, and very high frequencies for breeds originating in the
      Indian subcontinent. Consideration of breed frequencies in relation to breed
      type, shows low to moderate frequencies for the humpless breeds, high frequencies
      for the humped breeds. Various explanations for this distribution are discussed,
      among them the possibility that the Msp I (-) allele originated in the Bos
      indicus breeds of the Indian subcontinent, from which it diffused through the
      humpless Bos taurus breeds of Eastern Europe, the Mediterranean basin, eventually
      reaching Western, Northern Europe, Western Africa in low frequencies.

PMID- 10895315
TI  - Sequence and transfection of BoLA-DRB3 cDNAs.
AB  - Bovine MHC (BoLA-) DRB3 alleles encoded by the DH8A, DH22A and DH24A class II
      haplotypes were cloned from cDNA and characterized by sequence analysis.
      Comparison with other full-length DRB3 sequences suggested that DRB3 alleles may
      have evolved through multiple lineages. All three BoLA-DRB3 alleles were shown to
      express on the surface of transfected cells, and the transfectants were used to
      define or confirm the class II specificity of a panel of monoclonal antibodies.

PMID- 10895316
TI  - Evaluation of RDS/Peripherin and ROM1 as candidate genes in generalised
      progressive retinal atrophy and exclusion of digenic inheritance.
AB  - Generalised progressive retinal atrophy (gPRA) is a heterogeneous group of
      hereditary diseases causing degeneration of the retina in dogs and cats. As a
      combination of mutations in the RDS/Peripherin and the ROM1 genes leads to the
      phenotype of retinitis pigmentosa in man we first performed mutation analysis to
      screen these genes for disease causing mutations followed by the investigation of
      a digenic inheritance in dogs. We cloned the RDS/Peripherin gene and investigated
      the RDS/Peripherin and ROM1 genes for disease causing mutations in 13 gPRA
      affected dog breeds including healthy animals, obligate gPRA carriers and gPRA
      affected dogs. We screened for mutations using single strand conformation
      polymorphism (SSCP) analysis. Sequence analysis revealed several sequence
      variations. In the coding region of the RDS/Peripherin gene three nucleotide
      exchanges were identified (A277C; C316T; G1255A), one of which leads to an amino
      acid substitution (Ala339Thr). Various silent sequence variations were found in
      the coding region of the ROM1 gene (A536G, G1006A, T1018C, T1111C, C1150T,
      C1195T), as well as an amino acid substitution (G252T; Ala54Ser). By excluding
      the respective gene as a cause for gPRA several sequence variations in the
      intronic regions were investigated. None of these sequence variations
      cosegregated with autosomal recessively (ar) transmitted gPRA in 11 breeds. The
      candidate gene RDS/Peripherin obviously does not harbour the critical mutation
      causing the autosomal recessive form of gPRA because diseased individuals show
      heterozygous genotypes for sequence variations in the Miniature Poodle,
      Dachshund, Australian Cattle Dog, Cocker Spaniel, Chesapeake Bay Retriever,
      Entlebucher Sennenhund, Sloughi, Yorkshire Terrier, Tibet Mastiff, Tibet Terrier
      and Labrador Retriever breeds. In the following breeds the ROM1 gene was also
      excluded indirectly for gPRA: Miniature Poodle, Dachshund, Australian Cattle Dog,
      Sloughi, Collie, Tibet Terrier, Labrador Retriever and Saarloos/Wolfhound.
      Digenic inheritance for gPRA is practically excluded for both these genes in four
      breeds: Miniature Poodle, Dachshund, Labrador Retriever and Saarloos/Wolfhound.

PMID- 10895317
TI  - Dinucleotide repeat polymorphism at the ovine McMA7, McMA10, McMA13, McMA16,
      McMA17, McMA27, McMA29, McMA42, McMA47 and McMA49 loci.

PMID- 10895318
TI  - The porcine melanocortin-5 receptor (MC5R) gene: polymorphisms, linkage and
      physical mapping.

PMID- 10895319
TI  - Nine polymorphisms within the head and hinge region of the feline cardiac beta
      myosin heavy chain gene.

PMID- 10895320
TI  - Linkage and physical mapping of the sheep perforin (PRF1) gene to OAR 25.

PMID- 10895321
TI  - First seven microsatellites developed for the Peking duck (Anas platyrhynchos).

PMID- 10895322
TI  - Characterization of three PCR-RFLPs in an intron of the porcine liver- and red
      cell-type pyruvate kinase (PKLR) gene.

PMID- 10895323
TI  - The isolation and characterization of 34 equine microsatellite loci, TKY290
      TKY323.

PMID- 10895324
TI  - A highly polymorphic marker identified in intron 15 of the feline cardiac
      troponin T gene by SSCP analysis.

PMID- 10895325
TI  - Characterisation of 25 new physically mapped horse microsatellite loci: AHT24++
      48.

PMID- 10895326
TI  - Detection of a polymorphic 27 bp insertion/deletion in exon 4 of the canine
      calcitonin/calcitonin gene-related peptide gene I (CALCA).

PMID- 10895327
TI  - The equine CD74 gene has a polymorphic (CAG)n repeat in the 5'-untranslated
      region.

PMID- 10895329
TI  - An open invitation from the International Poverty and Health Network to all
      health professionals to combat poverty.

PMID- 10895328
TI  - Physical assignment of markers, SJ017, SJ042, and SJ065 to swine chromosome X.

PMID- 10895330
TI  - Cystoscopic diagnosis of bladder cancer by intravesical instillation of 5
      aminolevulinic acid induced porphyrin fluorescence--the Singapore experience.
AB  - OBJECTIVES: 1) To determine whether fluorescence cystoscopy after intravesical
      administration of 5-aminolevulinic acid (5-ALA) is more sensitive in detection of
      dysplasia and bladder cancer when compared with conventional cystoscopy. 2) To
      determine the safety of using 5-ALA. MATERIALS AND METHODS: A 3% 5-ALA solution
      was instilled intravesically before cystoscopy in 41 patients. The 5-ALA-induced
      porphyrin fluorescence was excited by violet light from a xenon arc lamp (lambda
      375-440 mm). RESULTS: Among the 175 biopsies obtained, the sensitivity of the
      fluorescence cystoscopy was greater than that of conventional cystoscopy (89.1%
      versus 65.6%, P < 0.05). Specificity was at 64.8% and 83.8% respectively with P <
      0.05. Duration of ALA instillation did not seem to affect the sensitivity and
      specificity of photodynamic diagnosis. The procedures were well tolerated by all
      patients with no additional complication. CONCLUSIONS: Fluorescence-guided
      biopsies are more sensitive than random biopsies in detecting dysplasia or
      bladder cancer without additional risk or complication. The duration of ALA
      instillation did not seem to affect the accuracy of photodynamic diagnosis.

PMID- 10895332
TI  - Adverse operative risk factors for perforated peptic ulcer.
AB  - INTRODUCTION: Mortality from perforated peptic ulcer still remains high as a
      result of more perforations in the elderly who are generally more ill. We
      conducted this retrospective study to determine the adverse operative risk
      factors for perforated peptic ulcers. MATERIALS AND METHODS: Two hundred and six
      consecutive patients operated for perforated peptic ulcers from 1 January 1993 to
      31 December 1997 were reviewed. RESULTS: Majority (n = 194) of the patients had
      perforations at the pyloroduodenal region and the remaining 10 patients had
      perforated benign gastric ulcers. The median age at surgery was 58 years (range
      18 to 91 years). Forty-four patients (21.4%) were more than 70 years old. The 30
      day operative mortality rate was 10.7% (n = 22). Advanced age (> 70 years),
      female gender, concurrent major medical illness, perforation developed while
      hospitalised for other medical illnesses, prolonged perforation (> 24 hours) and
      preoperative hypotension (systolic blood pressure < 90 mmHg) were indicators for
      operative mortality by univariate analysis. By logistic regression analysis, only
      concurrent major medical illness, prolonged perforation and preoperative
      hypotension were independent adverse risk factors. The operative mortality rate
      for patients with 0, 1, 2 and 3 independent adverse risk factors were 0%, 11%,
      30% and 88%, respectively. CONCLUSIONS: As concurrent medical illness is a non
      modifiable factor and preoperative hypotension is usually resulting from
      treatment delay and inadequate resuscitation, emphasis should place on shortening
      the time to surgery as well as prompt resuscitation.

PMID- 10895331
TI  - Philadelphia positive acute lymphoblastic leukaemia (ALL): clinico-haematologic
      characteristics, molecular analyses and 3-year follow up--a single institution
      study.
AB  - INTRODUCTION: The Philadelphia chromosome is one of the commonest chromosomal
      aberration in adult acute lymphoblastic leukaemia (ALL) patients. We present the
      results of a 3-year prospective study to look at the clinico-haematologic,
      immunophenotypic, cytogenetic and molecular profile of 13 adult patients with
      Philadelphia (Ph) positive ALL out of 35 newly diagnosed ALL seen at our
      institution over the past 3 years. MATERIALS AND METHODS: Thirty-five adult ALL
      patients seen between 1996 and 1998 comprised the study group. Marrow samples
      were obtained for immunophenotyping and karyotypic analysis at diagnosis. Samples
      were also obtained simultaneously for molecular testing for Ph chromosome.
      RESULTS: Thirteen patients were found to be Ph positive by molecular analysis
      while cytogenetic studies identified the chromosomal abnormality in 9 of these
      patients. The median age of our Ph positive patients was similar to those without
      Ph chromosome. Pre-B phenotype appears to be common in this group of patients. In
      concordance with other studies, Ph positive ALL was associated with a poor
      prognosis in our patients. CONCLUSION: Identification of Ph chromosome is
      important in the management of patients with ALL as it is an important prognostic
      marker.

PMID- 10895333
TI  - Perioperative and rehabilitative outcomes after amputation for ischaemic leg
      gangrene.
AB  - INTRODUCTION: Amputation of the severely ischaemic leg is often done when limb
      salvage is not possible or the patient is not fit enough for it. It is therefore
      important to determine the natural history of these amputees as our understanding
      of this will have significant impact on decision making. The aim of this study
      was to determine the early and late morbidity and mortality rates and
      rehabilitative outcome of these patients with lower limb amputation for end-stage
      arterial occlusive disease. MATERIALS AND METHODS: A retrospective study was done
      on 72 patients with 77 lower limb amputations for critical limb ischaemia (rest
      pain, gangrene, ischaemic ulcers) from 1993 to 1998 at the Singapore General
      Hospital. RESULTS: The mean age of the amputees was 69.7 years. Fifty-one per
      cent of the patients were male. Forty-five (58%) of the amputations were
      performed because the limb vasculature was not reconstructable, 12 (16%) because
      the limbs were too late for salvage and the remaining 20 (26%) because vascular
      reconstruction failed. Below knee amputations account for 63.6% of all
      amputations, above knee amputations account for 35.1% and through knee
      amputations account for 1.3%. Fifteen (19%) of the amputations had wound
      infection and 8% of amputations required re-amputation at a higher level for
      wound infection or failure of wound healing. The contralateral amputation rate
      was 21%. The 30-day mortality for all amputations was 11.1% and the commonest
      cause was acute myocardial infarction which accounted for 37.5%. Vascular
      reconstruction did not alter the overall or perioperative mortality rate.
      Cumulative survival figures showed that at the end of four years, only 38% of all
      amputees were still alive. 52.5% of amputees were wheelchair-bound, only 15% were
      household ambulators and 27.5% were community ambulators. Of all the patients
      with unilateral below knee amputations, 40% could walk out of home while only 20%
      of unilateral above amputations and 12.5% of bilateral below knee amputations
      could walk out of home. CONCLUSION: Early and late rehabilitation after
      amputation for critical limb ischaemia remain poor and efforts should be made to
      salvage critically ischaemic limbs wherever possible in patients who are fit
      enough.

PMID- 10895334
TI  - The predictive value of intraoperative ST-segment monitoring as a marker of
      myocardial injury.
AB  - AIM: To evaluate the usefulness of dynamic intraoperative ST-monitoring in high
      risk patients comparing it to preoperative clinical assessment and concurrent
      biochemical markers of cardiac injury. MATERIALS AND METHODS: Twenty-three
      patients clinically assessed as being at high risk for perioperative cardiac
      complications were recruited into this prospective, observational study in a
      public hospital. All had serial ECGs, cardiac enzymes and troponin-T
      measurements. The sensitivity, specificity, positive and negative predictive
      value of ST-segment changes in terms of predicting cardiac complications were
      calculated. We investigated the relationship between ST changes and biochemical
      markers of ischaemia and the predictive value of nonspecific (ASA) and specific
      (Goldman) clinical scores for cardiac complications. RESULTS: When correlated
      with cardiac complications, ST-segment monitoring had sensitivity 45.4%,
      specificity 100%, positive predictive value 100% and negative predictive value
      66.7%. The correlation with CK-MB and troponin T was sensitivity 16.7% and 25%,
      specificity 73.3% and 75%, positive predictive value 20% and 20%, and negative
      predictive value 68.8% and 80%, respectively. The percentage of patients with
      cardiac complications increased with poor Goldman and ASA clinical scores; 25%,
      40%, 62.5% and 100% in Goldman risk index groups of 0-5, 6-12, 13-25 and > 25,
      respectively; and 33.3% and 52.6% in ASA II and ASA III, respectively.
      CONCLUSIONS: This study demonstrates the importance of the anaesthesiologist
      preoperative assessment of cardiac risk. The probability that a patient with
      significant ST-depression will develop subsequent cardiac complications is 100%,
      which reflects its usefulness in this high-risk pre-selected sample. However, the
      test has a low sensitivity (45.4%).

PMID- 10895335
TI  - Audit of oxygen therapy in acute general medical wards following an educational
      programme.
AB  - INTRODUCTION: Previous studies have shown that the administration of
      supplementary oxygen (O2) in hospitalised patients outside the intensive care
      units (ICU) was usually empirical, inappropriate and not in compliance with
      physiological guidelines. It has been suggested that routine use of portable
      pulse oximeters in general wards plus in-service education of doctors and nurses
      may ameliorate this problem. MATERIALS AND METHODS: We introduced the use of
      pulse oximeters in general wards and instituted an educational programme on O2
      therapy in a University Hospital. We then audited the process of O2 therapy in
      100 consecutive adult medical inpatients. RESULTS: We found that, despite an
      educational programme and the easy availability of pulse oximeters, the quality
      of O2 therapy was poor. Half the patients did not receive objective pre-treatment
      assessment while 43% of patients were not adequately reassessed after O2
      supplementation had been started. The most common error was excess use of O2
      which occurred in 75% of patients. CONCLUSION: The quality of O2 therapy in the
      non-ICU setting was poor. Excessive O2 use was the most common error. We suggest
      that titration of O2 therapy, guided by pulse oximeter-guided protocols, may be
      needed to improve the quality and reduce the cost of O2 therapy in the hospital.
      This intervention may best be instituted within the environment of a continuous
      quality improvement model of health care delivery.

PMID- 10895337
TI  - Surgical results of intercondylar fractures of the adult femur.
AB  - INTRODUCTION: Although surgical treatment of intercondylar fractures of the adult
      femur gives satisfactory results in the majority of cases, there are
      complications reported with operative management. We aim to analyse the surgical
      results of these cases performed in our institution and compare them to other
      reported series. MATERIALS AND METHODS: A total of 16 patients with intercondylar
      fractures of the femur were operatively treated from 1989 to 1997. The ages of
      these patients ranged from 24 to 77 years, with a mean age of 42 years. Average
      length of follow-up was 28 months. The fractures were classified according to AO
      classification. Twenty-five per cent of the fractures were significantly
      comminuted. They were internally fixed with various implants such as cancellous
      screw fixation, dynamic condylar screw plate, condylar blade plate and condylar
      buttress plate. RESULTS: Average time to full weight bearing was 12 weeks.
      Results of treatment were assessed according to the criteria described by
      Shelbourne. Eighty-three per cent of minimally comminuted fractures had a good
      result, but only 50% of significantly comminuted fractures did well. CONCLUSIONS:
      We recommend the use of anterior midline approach and condylar buttress plate for
      very comminuted fractures. Infection, if detected early and treated aggressively
      could avoid a poor outcome. Elderly patients should benefit from internal
      fixation and earlier mobilisation.

PMID- 10895336
TI  - Total intravenous anaesthesia using 3-in-1 mixture of propofol, alfentanil and
      mivacurium.
AB  - INTRODUCTION: To avoid errors and confusion associated with 3 separate infusions,
      we conducted a feasibility study of total intravenous anaesthesia (TIVA) using 1
      electrically-powered syringe pump to deliver a 3-in-1 mixture containing fixed
      proportions of propofol, alfentanil and mivacurium. MATERIALS AND METHODS: The 3
      in-1 mixture was obtained by mixing 200 mg propofol, 1 mg alfentanil, 20 mg
      mivacurium, and making up to 40 mL with 5% dextrose solution. Electrical zone
      sensing sizer and light microscopy were used to compare emulsion instability of
      the 3-in-1 with control mixtures. In 50 ASA 1 patients, bolus infusions of 0.4 mL
      of the 3-in-1 mixture per kg body weight were given for induction of anaesthesia.
      All patients were subsequently intubated and ventilated with air-oxygen mixtures.
      Anaesthesia was maintained using a continuous infusion of the 3-in-1 mixture with
      the infusion rate titrated to satisfactory clinical response. Intravenous
      morphine 0.1 mg/kg was given for intra- and postoperative analgesia. Residual
      neuromuscular blockade was reversed using glycopyrronium and neostigmine at the
      end of surgery. RESULTS: The 3-in-1 mixtures remained stable for up to 5 hours
      after preparation. Induction and maintenance of anaesthesia were smooth,
      intubation conditions satisfactory, and intraoperative haemodynamic changes
      acceptable. Recovery from anaesthesia and neuromuscular blockade was rapid. There
      were no major intra- or immediate postoperative complications. CONCLUSIONS: The 3
      in-1 mixtures remained stable for up to 5 hours after preparation. It may be
      feasible to provide TIVA using the 3-in-1 mixture for induction and maintenance
      of anaesthesia in ASA 1 patients.

PMID- 10895338
TI  - Initial experience of radiofrequency catheter ablation of supraventricular
      tachycardia in paediatric patients.
AB  - INTRODUCTION: The management of supraventricular tachycardia (SVT) in paediatric
      patients until recently has frequently been pharmacologic therapy, but this
      approach suffers from the drawbacks of treatment failure, development of drug
      intolerance and/or side-effects. AIM: In keeping with recent advances in
      paediatric cardiology, we share our experience with radiofrequency catheter
      ablation as an alternative and definitive modality of therapy. MATERIALS AND
      METHOD: 4 young patients with recurrent SVT underwent electrophysiologic study
      followed by radiofrequency ablation of the accessory pathways. RESULTS:
      Resolution of symptoms was achieved in all patients and no major complication was
      encountered. CONCLUSIONS: The ability to ablate permanently the reentrant circuit
      responsible for SVT has now permitted cure by non-surgical means, and is an
      important alternative to drug therapy in the management of SVT in children.

PMID- 10895339
TI  - Microdochectomy for single-duct nipple discharge.
AB  - INTRODUCTION: Isolated single-duct nipple discharge is worrying and poses a
      surgical dilemma. Factors predicting malignancy are controversial. MATERIALS AND
      METHODS: Retrospective review of 92 consecutive microdochectomies for single-duct
      nipple discharge in a tertiary referral centre over 8 years. RESULTS: The
      commonest causes were ductal papilloma (52%) and fibrocystic diseases of the
      breast (21%). Five (5%) patients had breast carcinoma, of whom only 1 had an
      invasive component. The median age of these patients was 43 years (range 26 to 72
      years) which was similar to median age of the whole cohort. Sixty-seven (73%)
      patients presented with blood-stained nipple discharge. The 5 patients with
      breast carcinoma had blood-stained discharge. Mammography was abnormal in 1 out
      of 4 patients in the carcinoma group. CONCLUSIONS: The incidence of breast
      carcinoma in patients presenting with isolated single-duct nipple discharge was
      low (5%) among Singaporean women. There was no reliable predictors of malignancy,
      though all patients with carcinoma presented with blood-stained discharge.
      Microdochectomy still remains an effective treatment for nipple discharge both
      for cure and diagnosis.

PMID- 10895340
TI  - Six-year follow-up of untreated T1 carcinoma of prostate.
AB  - INTRODUCTION: The management of T1 carcinoma of prostate remains controversial
      and the critical role of histopathology is often underestimated. MATERIALS AND
      METHODS: A retrospective review was conducted on 27 cases of T1 prostate
      carcinoma diagnosed between 1980 and 1992, all of which were managed on a
      surveillance programme. Pathological material of 24 cases was available for re
      examination by a single histopathologist without prior knowledge of the
      originally assigned grade. Gleason's scoring system was used in the current
      review. RESULTS: Twenty-two (81.5%) were T1a and 5 (18.5%) T1b. Mean duration of
      follow-up was 77.3 months (1.0 to 159.0) and median age was 72.0 years (61.0 to
      84.0). Twenty-five (92.6%) were originally graded as well differentiated, 1
      (3.7%) was moderately differentiated and 1 (3.7%) was poorly differentiated.
      Three of the well-differentiated tumours were upstaged because of tumour volume.
      On review, differences in grading were noted in 13 cases (54.2%) and 11 (45.8%)
      were, as a consequence, upstaged. Progression was recorded in 5 cases (18.5%).
      Mean disease-free interval was 47.6 months (7.0 to 75.0) and mean serum PSA at
      progression was 34.2 ug/l (2.3 to 62.5). Four responded to delayed therapy.
      Mortality was recorded in 13 cases (48.1%) but cancer-specific mortality was only
      7.7% (1/13). Mean age at death was 78.1 years. CONCLUSION: The importance of
      accurate grading and staging cannot be overemphasized given its pivotal role in
      subsequent management. The impact of age is also apparent and surveillance
      appears a reasonable option for those with limited life expectancy after
      diagnosis.

PMID- 10895341
TI  - DNA testing for fragile X syndrome in 255 males from special schools in
      Singapore.
AB  - INTRODUCTION: Fragile X syndrome, the most common cause of inherited mental
      retardation, results from unstable expansion of a trinucleotide (CGG)n repeat in
      the FMR1 gene. Phenotypic expression is variable making clinical diagnosis
      difficult, while diagnosis by Southern blotting is relatively expensive and
      labour intensive. The prevalence in Singapore has not been studied. MATERIALS AND
      METHODS: We developed a rapid screening test using a PCR analysis. We studied 255
      males with unexplained cause for learning difficulties from 8 special schools. A
      clinical scoring system based on characteristic features described was devised.
      RESULTS: PCR analysis showed absence of the band for the normal allele in 11
      samples, 6 of which were confirmed by Southern blotting to be positive for FMR1
      expansion, giving a 2% false-positive rate with PCR. Sensitivity of the PCR test
      was evaluated by performing Southern blotting in all PCR-normal samples; all of
      which were confirmed to be normal. This PCR test was shown to be highly
      reproducible. Clinical criteria were not predictive. CONCLUSIONS: Six (2.4%) new
      cases of fragile X syndrome were detected. There is a need to incorporate fragile
      X testing in routine screening of patients with developmental delay and learning
      difficulties. The use of PCR could eliminate the need for Southern blotting in up
      to 95% of cases. PCR analysis provides a simple, reliable and rapid tool for
      screening.

PMID- 10895342
TI  - A rational alternative for the diagnosis of diabetes mellitus in high risk
      individuals.
AB  - INTRODUCTIONS: To facilitate early, accurate diagnosis, tests should be easy,
      cheap and reproducible. We studied volunteers with an increased risk of
      developing diabetes mellitus (DM) to see if HbA1c levels could replace the oral
      glucose tolerance test (OGTT) in diagnosing DM. MATERIALS AND METHOD: One hundred
      and eleven individuals were studied, using the standard oral glucose tolerance
      test, and simultaneous measurement of HbA1c levels. Receiver operator
      characteristic (ROC) analysis was performed to assess the sensitivity and
      specificity of various HbA1c cut-off levels for diagnosing DM. The relationship
      between fasting plasma glucose (FPG) and DM diagnosis was also investigated.
      RESULTS: The majority of DM and impaired glucose tolerance (IGT) cases were
      diagnosed on the basis of two-hour OGTT glucose values. If FPG alone had been
      used, 29% of the study population with DM or IGT would have been missed. HbA1c
      cut-off of 6.2% or 6.3% gives the optimal sensitivity and specificity. In linear
      regression analysis, FPG was found to be a significant predictor of 2-hour OGTT,
      but only accounted for 45% of the variability of 2-hour OGTT glucose value.
      CONCLUSIONS: Our data support the view that although HbA1c alone cannot replace
      the OGTT in the diagnosis of DM, it can still provide a useful guide to rational,
      cost-effective screening for diabetes mellitus.

PMID- 10895343
TI  - Classical and amyopathic dermatomyositis seen at the National Skin Centre of
      Singapore: a 3-year retrospective review of their clinical characteristics and
      association with malignancy.
AB  - INTRODUCTION: Dermatomyositis is a condition well-known to medical physicians,
      especially rheumatologists and dermatologists. Classically, patients present with
      typical cutaneous features and proximal muscle weakness. Amyopathic
      dermatomyositis has been reported in recent literature where patients present
      with skin changes without muscle involvement. MATERIALS AND METHODS: We reviewed
      28 patients diagnosed with dermatomyositis at the National Skin Centre over a 3
      year period from 1996 to 1998 to assess the prevalence of this amyopathic variant
      in our local population and its association with malignancy. RESULTS: Out of the
      28 patients, 13 (46.4%) had no clinical or laboratory evidence of myositis at
      presentation. Nine patients (32.1%) had clinical muscle weakness and 6 patients
      (21.4%) had laboratory evidence of myositis. Malignancies were detected in 12
      patients (42.8%), half of which were nasopharyngeal carcinomas. There was no
      significant difference in the prevalence of malignancy between those with
      detectable muscle weakness (33.3%) and those without (47.4%). However, there was
      a significant higher prevalence of malignancy in those with clinical and
      laboratory evidence of myositis (66.6%) than those without (15.4%). CONCLUSION:
      We conclude that amyopathic dermatomyositis is a common presentation in our
      population and may have a lower risk of malignancy than the classical variant.
      Screening for malignancy, especially nasopharyngeal carcinoma, is recommended for
      all dermatomyositis patients.

PMID- 10895344
TI  - Technetium-99m sestamibi for the assessment of myocardial salvage following
      reperfusion therapy in acute myocardial infarction.
AB  - INTRODUCTION: Reperfusion therapy with either thrombolysis or angioplasty has
      been shown to be beneficial in acute myocardial infarction. Tc-99m sestamibi is a
      myocardial tracer that can be used to assess myocardial salvage because of its
      property of very limited redistribution. MATERIALS AND METHODS: To assess the
      feasibility of this technique locally, Tc-99m sestamibi was injected before and
      after reperfusion therapy with angioplasty (n = 11) or streptokinase (n = 18) in
      29 patients with acute myocardial infarction (anterior = 25, inferior = 4).
      Single-photon emission computed tomography (SPECT) was performed within 4 hours
      of reperfusion and repeated 5 to 7 days later. RESULTS: Initial perfusion defect
      size ranged from 6% to 78% (mean 36.3 +/- 18.7%), and final defect size from 0%
      to 50% of the left ventricle (mean 23.7 +/- 14.8%, P < 0.001). Patients with
      proximal left anterior descending artery (LAD) lesions had larger defects
      compared to those with mid LAD lesions (mean defect size 52% for pLAD versus 28%
      for mLAD, P < 0.013). However, there were wide variations in initial defect size
      (myocardium at risk) for a given infarct-related artery location. The mean
      decrease in defect size was 12% in the 28 patients with patent arteries compared
      to only 2% in the patient with an occluded artery (47% to 45%). There was no
      significant difference in amount of salvage between patients who had thrombolysis
      (mean 13%, P = 0.0003) and patients who had percutaneous transluminal coronary
      angioplasty (PTCA) (mean 12%, P = 0.005). CONCLUSIONS: Assessment of myocardial
      salvage is feasible using Tc-99m sestamibi SPECT imaging. It allows for
      quantitation of myocardium at risk and the amount of myocardial salvage, which is
      not possible by angiography alone.

PMID- 10895345
TI  - Incidence of ischaemic heart disease and stroke in Chinese, Malays and Indians in
      Singapore: Singapore Cardiovascular Cohort Study.
AB  - INTRODUCTION: This is the first prospective cohort study in Singapore to describe
      the incidence of ischaemic heart disease (IHD) and stroke among Chinese, Malays
      and Asian Indians. MATERIALS AND METHODS: The Singapore Cardiovascular Cohort
      Study is a longitudinal follow-up study on a general population cohort of 5920
      persons drawn from 3 previous cross-sectional surveys. Morbidity and mortality
      from IHD and stroke were ascertained by record linkage using a unique
      identification number with the death registry, Singapore Myocardial Infarct
      Registry and in-patient discharge databases. RESULTS: There were 193 first IHD
      events and 97 first strokes during 52,806 person-years of observation. The
      overall incidence of IHD was 3.8/1000 person-years and that of stroke was
      1.8/1000 person-years. In both males and females, Indians had the highest IHD
      incidence, followed by Malays and then Chinese. For males after adjusting for
      age, Indians were 2.78 times (95% CI 1.86, 4.17; P < 0.0001) and 2.28 times (95%
      CI 1.34, 3.88; P = 0.002) more likely to get IHD than Chinese and Malays
      respectively. For females after adjusting for age, Indians were 1.97 times (95%
      CI 1.07, 3.63; P = 0.03) and 1.37 times (95% CI 0.67, 2.80; P = 0.39) more likely
      to get IHD than Chinese and Malays respectively. For stroke, male Chinese and
      Indians had higher incidence than Malays (though not statistically significant).
      However, in females, Malays had the highest incidence of stroke, being 2.57 times
      (95% CI 1.31, 5.05; P = 0.008) more likely to get stroke than Chinese after
      adjustment for age. CONCLUSIONS: This prospective study of both mortality and
      morbidity has confirmed the higher risk of IHD in Indians. It has also found that
      Malay females have a higher incidence of stroke, which deserves further study
      because of its potential public health importance.

PMID- 10895346
TI  - Screening for hearing impairment in hospitalised elderly.
AB  - OBJECTIVES: The objective of this study was to determine the prevalence of
      hearing impairment in hospitalised elderly patients using the Welch Allyn
      Audioscope 3. PATIENTS AND METHOD: Consecutive geriatric patients admitted to an
      acute 38-bedded geriatric ward over a 4-week period in 1998 were screened for
      hearing impairment. The examination was conducted in a quiet side-room adjacent
      to the ward. Ability to hear normal conversation at arm's length and the
      whispered voice were noted. A conventional auroscopy was done. Screening using
      Welch Allyn Audioscope 3 was then conducted at 40 dB using speech frequencies of
      500, 1000 and 2000 Hz. Individuals who failed to respond at any 2 frequencies in
      the better ear were deemed to have significant hearing impairment. Patients with
      impacted earwax had repeat audioscopic examination after wax was cleared.
      RESULTS: One hundred and twenty-four patients were enrolled. Fifty-four patients
      were excluded from the study: 37 patients had dementia, 11 were critically ill, 5
      were dysphasic while 1 had acute confusion. The remaining 70 patients were
      included in the study. The median age of the study group was 81 years (range 72
      to 96 years). There were equal number of males and females. Forty-seven (67.1%)
      patients had hearing impairment. Nineteen (40.4%) out of 47 hearing-impaired
      patients could not hear normal conversation at arm's length while 34 (72.3%) out
      of the same 47 patients failed the whispered voice test. Only 22 (46.8%) hearing
      impaired patients complained of hearing difficulties. Four out of the 47 hearing
      impaired patients possessed hearing aids. Majority (83.0%) of patients with
      hearing impairment did not want hearing aids and cited "no necessity" as the main
      reason for not wanting them. Five (7.1%) and 12 (17.1%) patients had bilateral
      and unilateral impacted ears respectively. Two out of 20 ears cleared of wax
      improved by one tone on repeat auroscopy. CONCLUSION: The prevalence of hearing
      impairment in hospitalised elderly patients was found to be very high during
      screening with an audioscope. However, identification of hearing impairment using
      the audioscope was not associated with keenness of wanting a hearing aid. The
      important factors associated with keenness for wanting a hearing aid were
      difficulty with hearing conversation at arm's and complaint about being
      handicapped socially by hearing difficulty. Screening for hearing impairment
      should be part of the routine in the examination of a hospitalised elderly as the
      prevalence of the disease is very high. Ability to hear normal conversation at
      arm's length alone was not a reliable method of screening for hearing impairment
      and it should be complemented by the whispered voice test. The audioscope is an
      expensive instrument and not widely available. Although the audioscope screening
      method was able to pick up more cases of hearing impairment, it did not result in
      more patients wanting hearing aid. Those detected to have hearing impairment will
      require further counselling regarding the usefulness of a hearing aid and
      detailed audiological assessment if they are keen for a hearing aid.

PMID- 10895347
TI  - Upper airway resistance syndrome--report of three cases.
AB  - INTRODUCTION: Patients with the upper airway resistance syndrome are frequently
      overlooked, and even if clinically suspected, often escape identification by
      polysomnographic monitoring. CLINICAL PICTURE: Three cases (2 women and a man)
      with excessive daytime sleepiness and fatigue were confirmed to have the upper
      airway resistance syndrome after undergoing polysomnography with oesophageal
      pressure monitoring. TREATMENT: Nasal CPAP during sleep was prescribed for 2
      cases but 1 case refused all available treatment options. OUTCOME: After one
      month of CPAP therapy, the 2 cases reported improved symptoms and Epworth
      sleepiness scores. Lower daytime blood pressures were also recorded. CONCLUSIONS:
      Oesophageal pressure monitoring and EEG arousal analysis can greatly enhance the
      diagnostic accuracy in the upper airway resistance syndrome. Accurate diagnosis
      and effective treatment of this condition is important because of its sequelae of
      hypersomnolence and association with other disorders like systemic hypertension.

PMID- 10895348
TI  - A case report of Aspergillus hypersensitivity syndrome with obstructing bronchial
      aspergillosis.
AB  - INTRODUCTION: A 62-year-old Indian male with diabetes mellitus presented with
      atypical, overlap features of Aspergillus hypersensitivity syndrome and
      obstructing bronchial aspergillosis. CLINICAL PICTURE: He was febrile and
      tachypnoeic with diffuse crepitations and wheezing. Chest X-ray was normal but
      eosinophil count was 2900/mm3 and Ig E > 10,000 IU/ml. TREATMENT AND OUTCOME: He
      responded initially to high dose steroid therapy but deteriorated subsequently
      from extensive mucus plugging of the bronchial tree which resulted in respiratory
      failure and death. He was HIV-negative. CONCLUSION: Culture and histologic
      examination of bronchoscopically identified tracheobronchial mucus plugs should
      be performed as early treatment may be life-saving.

PMID- 10895349
TI  - An unusual case of cutaneous vasculitis.
AB  - INTRODUCTION: We report an unusual case of a patient with clinical and
      histological features of cutaneous vasculitis. CASE PICTURE: A middle-aged
      Chinese male presented with livedo reticularis and digital gangrene without
      visceral involvement. Skin biopsy showed features suggestive of cutaneous
      vasculitis. Repeated testing for anticardiolipin antibody was negative.
      TREATMENT: He was treated with two courses of intravenous prostacyclin and pulsed
      with one course of intravenous methylprednisolone. He was also put on oral
      prednisolone, pentoxifylline, aspirin, nifedipine and colchicine in addition to
      symptomatic therapy. OUTCOME: There was gradual improvement of his toe
      discolouration and relief of pain. CONCLUSIONS: This is an interesting case of
      cutaneous vasculitis, which has features of polyarteritis nodosa and the
      antiphospholipid syndrome, who responded well to intravenous prostacyclin,
      steroids, pentoxifylline, aspirin, nifedipine and colchicine.

PMID- 10895350
TI  - Candida arthritis in a premature infant treated successfully with oral
      fluconazole for six months.
AB  - INTRODUCTION: Candida arthritis in premature infants is a rare condition mainly
      treated with parenteral amphotericin B. CLINICAL PICTURE: Arthritis 9 weeks after
      birth. The infection resulted out of colonisation at birth and fungaemia at day 6
      and day 13 of life. TREATMENT: Oral fluconazole for 6 months (5 mg/kg/day after
      loading with 7 mg/kg/day). OUTCOME: Full remission. CONCLUSIONS: Oral fluconazole
      is an alternative to parenteral amphotericin B in the treatment of premature
      infants, but proof of absorption and an extended treatment period according to
      prematurity might be warranted.

PMID- 10895351
TI  - Subcutaneous emphysema and pneumomediastinum after endotracheal anaesthesia.
AB  - INTRODUCTION: We report a case of subcutaneous emphysema and pneumomediastinum
      that presented postoperatively after tracheal extubation. CLINICAL PICTURE: A 51
      year-old man had an uneventful anaesthesia lasting about 6.5 hours. Intubation
      was performed by a very junior medical officer and was considered difficult. He
      developed sore throat, chest pain, numbness of both hands and palpable crepitus
      around the neck postoperatively. Chest X-ray revealed diffuse subcutaneous
      emphysema, pneumomediastinum and possible pneumopericardium. TREATMENT: He was
      treated conservatively with bed rest, oxygen, analgesia, antibiotic prophylaxis,
      reassurance and close monitoring. OUTCOME: The patient made an uneventful
      recovery. CONCLUSIONS: We discussed the possible causes.

PMID- 10895352
TI  - Transurethral surgery and the adductor spasm.
AB  - INTRODUCTION: Transurethral surgery has become the dominant treatment for bladder
      and prostatic tumours. Regional anaesthesia is the favoured anaesthetic technique
      but adductor spasm leading to bladder wall perforation and increased morbidity is
      not uncommon. This review seeks to outline the cause, risk factors predisposing
      to this complication and the various techniques that have been adopted to
      eradicate it. METHODS: Literature search was performed from PubMed (1965
      onwards). All studies related to obturator nerve stimulation or adductor spasm in
      transurethral surgery were short-listed. RESULTS: Various methods have been
      attempted. These ranged from local blockade of the obturator nerve, periprostatic
      and subvesical lignocaine infiltration, changing the site of the inactive
      electrode, reduction of the electrocoagulation voltage and general anaesthesia
      with muscle relaxants. CONCLUSIONS: Hitherto, local blockade of the obturator
      nerve, either by the direct method or "3-in-1" method is the most effective in
      preventing this complication. With the aid of a nerve stimulator, greater
      accuracy and use of smaller volumes of local anaesthetic will improve the safety
      of this block.

PMID- 10895353
TI  - Association or agreement.

PMID- 10895354
TI  - 4th Yahya Cohen Lecture. Management of growth arrest with tissue-engineered
      cells.

PMID- 10895355
TI  - 3rd Tan Tock Seng Hospital oration: the changing fabric of medicine--an ethical
      and social revolution.

PMID- 10895356
TI  - A systematic review of effective cognitive-behavioural supervision.
AB  - OBJECTIVES: A systematic review was undertaken of studies that have assessed
      objectively the impact of supervision and consultancy. As well as gauging
      effectiveness, we examined the methodological rigour of these studies. METHOD:
      Twenty-eight empirical studies of the change processes occurring between
      participants within the educational pyramid, 'consultant-->supervisor',
      'supervisor-->supervisee' and 'supervisee-->patient', were analysed. The
      inclusion criteria also required that supervision was analysed under field
      conditions and there were objective measures of learning outcomes. Each study was
      analysed by reference to an evaluation manual, with two independent raters
      obtaining satisfactory reliability. RESULTS: Studies meeting the above criteria
      came mainly from the intellectual disability specialty and included many studies
      using cognitive-behavioural methodologies. The studies included in this sample
      had more rigorous methodologies than those reviewed by Ellis, Ladany, Krengel,
      and Schult (1996). The findings of the review suggested that the pyramid approach
      benefited patients. Closely monitoring the supervisee, modelling competence,
      providing specific instructions, goal setting and providing contingent feedback
      on performance were the dominant methods of supervision and were associated with
      benefits to supervisees. CONCLUSION: Despite the large body of literature on
      supervision, there have been relatively few empirical investigations of the
      educational pyramid. This work identified a number of studies with good
      methodological rigour, although these too often failed to provide adequate
      background and assessment details regarding each of the members of the pyramid,
      particularly the consultant. The results of cognitive-behavioural supervision
      were found to be positive.

PMID- 10895357
TI  - The effect of extended family living on the mental health of three generations
      within two Asian communities.
AB  - BACKGROUND: A study by Shah & Sonuga-Barke (1995) identified a relationship
      between family structure and the mental health of Pakistani Muslim mothers and
      their children. Children in extended families fared better, but their mothers
      fared worse than their nuclear family counterparts. The present study replicates
      and extends this study by exploring the impact of nuclear and extended family
      living on the mental health of three generations (children, mothers and
      grandmothers) in British Hindu as well as Muslim communities. METHOD: 44 Muslim
      and 42 Hindu families participated in the study. The mental health of mothers and
      grandmothers and the behavioural problems of children (aged 5-11) were examined.
      Both mothers and grandmothers completed the Hospital Anxiety and Depression
      Scale. The children's behavioural adjustment was rated by their teachers using
      the Rutter Scale. Other relevant variables such as acculturation levels were also
      measured. RESULTS: Children and grandmothers were better adjusted in extended
      families than nuclear families. In contrast, mothers were better adjusted in
      nuclear families. This interaction between family type and generation was evident
      in both Muslim and Hindu families and did not appear to be mediated by other
      variables such as acculturation. Furthermore, mothers' and childrens' adjustment
      was significantly correlated with grandmothers', but not mothers', mental health
      in extended families (although not in nuclear families). DISCUSSION: These
      results provide further evidence for the link between family structure and mental
      health in Asian communities. They also challenge some of the assumptions about
      maternal mental health, its effects on child adjustment and its links to systems
      of social support. In extended families where social support was likely to be
      most available mothers were at greatest risk, while their children profited and
      this advantage seemed to be linked to the grandmaternal presence.

PMID- 10895358
TI  - Associations between primary appraisals and life-events while controlling for
      depression.
AB  - OBJECTIVES: The main objective of this paper was to explore the associations
      between life-events and primary appraisals (threat, challenge and loss)
      controlling for depression. It was predicted that specific associations between
      life-events and primary appraisals would remain once depression had been
      partialled. A subgoal of this paper was to develop a content analytic coding
      frame for student life-events. DESIGN: This study was a retrospective survey in
      which participants provided accounts of recent stressful encounters, and
      completed indices of primary appraisals and depression. METHOD: The participants
      were 979 undergraduates who provided descriptions of life-events. A subsample of
      391 provided additional information on primary appraisals and depression. The
      primary outcomes were the partial correlations between life-events and primary
      appraisals. RESULTS: There were significant associations between life-events and
      primary appraisals above and beyond variance explained by depression. Results
      also indicated that the definition of loss appraisals could be extended to
      include events that were related to anticipated future loss, especially if the
      event was also perceived as threatening. Also certain self-defined negative life
      events were appraised as positive. Life-events were shown to vary systematically
      as a function of external constraints (e.g. stage of the academic year).
      CONCLUSIONS: A variety of events were associated with loss appraisals and this
      may have implications for risk factors in depression.

PMID- 10895359
TI  - Carers' attributions for challenging behaviour.
AB  - OBJECTIVES: The purpose of this study was to apply Weiner's (1986) attributional
      model of helping to the care of clients presenting with challenging behaviour. A
      number of predictions were tested: (a) that aggressive, destructive, and self
      injurious behaviours would differentially affect carers' ratings of attributional
      dimensions; (b) that carers' propensity to help would be mediated by positive
      affect rather than optimism; (c) that optimism would be reduced by a perceived
      stable cause, such as client's level of dependency. DESIGN AND METHOD: The
      participants were 50 care staff working in challenging behaviour day services,
      who were presented with six case studies to rate. A two-factor repeated measures
      design was employed to examine the effects of challenging behaviour and
      dependency on carers' ratings of attributional dimensions, affects, optimism and
      helping. Correlational analysis was employed to examine the relative effects of
      positive affect, negative affect and optimism on carers' propensity to help.
      RESULTS: All three predictions were confirmed. The more independent and outer
      directed the challenging behaviour, the greater the carers' attributions of
      control and negative affect, and the less the propensity to help. The more self
      directed and dependent the client's challenging behaviour, the greater the
      carers' attribution of stability, positive affect and propensity to help.
      CONCLUSIONS: The results are discussed in relation to the concept of helping and
      the experience of carers coping with challenging behaviours.

PMID- 10895360
TI  - Factor analysis of three standardized tests of memory in a clinical population.
AB  - OBJECTIVES: The aim of this study was to determine the factor structure of three
      standardized memory tests: Wechsler Memory Scale-Revised (WMS-R), Warrington
      Recognition Memory Test (WRMT), Doors and People Test (D&P). We investigated
      whether these different standardized tests of memory are consistent in their
      evaluation of memory function, and the extent to which these tests discriminate
      between different memory functions (e.g. recall/recognition and verbal/non-verbal
      memory). DESIGN: Fifty patients with selective memory impairment were tested on
      the WMS-R, WRMT and D&P. METHODS: Age-scaled scores from selective measures of
      these tests (WMS-R-verbal, WMS-R-visual, WMS-R-delay, WRMT-words, WRMT-faces, D&P
      people, D&P-doors, D&P-shapes, D&P-names) were used as input to a factor
      analysis. RESULTS: Maximum likelihood factor analysis yielded a three-factor
      solution consistent with a theoretically motivated fractionation of memory
      function into recall and recognition components. Recognition performance, but not
      recall performance, showed dissociation into visual and verbal components.
      CONCLUSIONS: The WMS-R, WRMT and D&P are highly consistent in their assessment of
      memory function. The results of the factor analysis are consistent with a
      theoretically motivated fractionation of recall and recognition memory. They are
      also partially consistent with a dissociation between visual and verbal memory
      function.

PMID- 10895361
TI  - Short test of semantic and phonological fluency: normal performance, validity and
      test-retest reliability.
AB  - Tests of verbal fluency, whether of Semantic Fluency (SF) or Phonological Fluency
      (PF), are often used as a standard method of neuropsychological assessment.
      However, very little normative data, standardized on a UK sample, is available,
      and little is known about the utility of popularly used 'short-forms' of these
      tasks. Additionally, very little is known about verbal fluency test-retest
      reliability. In this report we describe the performance of N = 365 normal
      participants on a version of SF requiring the generation of exemplars of the
      category 'animals' and a version of the PF task requiring participants to
      generate words beginning with the letter 'B'. From this data we have derived a
      percentile distribution for both tasks. We also addressed the impact of sex, age,
      years of education and IQ upon both SF and PF performance. No sex differences
      were found on either the PF or the SF tasks. A significant but small correlation
      between age and SF, but not PF, was observed. Modest correlations between both
      years of education and IQ and PF and SF performance were also seen. We also
      report test-retest reliability scores for performance on both SF and PF tasks.
      Performance on the longer 'FAS' version was found to correlate highly with scores
      obtained using just the letter 'B'. This suggests that little additional
      advantage obtains from administering three-letter versions of PF. An extremely
      high degree of correlation between SF tasks in which participants are given 1
      minute and scores obtained when participants are given 1 minute 30 seconds was
      also observed. Finally, in order to assist users in deciding whether a changed
      retest score is due to error measurement or a real effect, we calculated Standard
      Error of Prediction (SEP) scores.

PMID- 10895362
TI  - Differential environmental factors in anorexia nervosa: a sibling pair study.
AB  - OBJECTIVES: Previous studies have explored differences in psychosocial and
      familial factors between women who develop anorexia nervosa and those who do not.
      However, these studies have generally used between-group comparisons. This study
      looks at the environmental factors which may be antecedents of anorexia nervosa
      looking at sister pairs where one had anorexia nervosa and the other did not.
      DESIGN: A paired design was used to compare anorexic women with an unaffected
      sister on a number of background variables, including sibling interaction,
      parental care, peer group characteristics and other events unique to the
      individual. METHODS: The Sibling Inventory of Differential Experience (SIDE) was
      used to determine non-shared environment. Out of an initial sample of 148 women
      with past or current anorexia nervosa, 28 were identified who had sisters with no
      reported history of eating disorders and who also consented to complete the
      questionnaire. RESULTS: Anorexic sisters perceived more maternal control and
      reported more antagonism towards and jealousy of their sisters than did
      unaffected sisters. In addition, anorexic women reported having had fewer friends
      and boyfriends than their sisters. CONCLUSIONS: These results confirm the
      perceived differences in background environment between women with and women
      without anorexia nervosa. These issues are discussed in relation to behavioural
      genetics, family dynamics and psychosexual development.

PMID- 10895363
TI  - The relationship between parental bonding and core beliefs in anorexic and
      bulimic women.
AB  - OBJECTIVE: The role of core beliefs in the psychopathology of eating disorders
      has been considered in recent years. Young (1994) hypothesized that unhealthy
      core beliefs originate from the experience from the first few years of life. The
      aim of the present study was to consider whether perceived parental bonding might
      explain the development of such beliefs in eating disordered women. METHOD: The
      participants were 30 anorexics, 27 bulimics and 23 comparison women who completed
      measures of core beliefs and perceived parental bonding. RESULTS: There were
      significant differences in perceived parental bonding behaviours across groups.
      The association between parental bonding and core beliefs were much stronger in
      the anorexic group than that in either the bulimic or the control group. In
      particular, a perceived low level of parental care was predictive of the presence
      of some unhealthy core beliefs in anorexic women. CONCLUSION: Longitudinal
      research is needed to confirm these findings among anorexic and bulimic women.
      Clinically, these findings provide insight into the possible origins or core
      beliefs, and hence might aid their challenge in schema-focused cognitive therapy.

PMID- 10895364
TI  - Underlying assumptions and core beliefs in anorexia nervosa and dieting.
AB  - OBJECTIVE: To investigate assumptions and beliefs in anorexia nervosa and
      dieting. DESIGN AND METHOD: The Eating Disorder Belief Questionnaire (EDBQ), was
      administered to patients with anorexia nervosa, dieters and female controls.
      RESULTS: The patients scored more highly than the other two groups on assumptions
      about weight and shape, assumptions about eating and negative self-beliefs. The
      dieters scored more highly than the female controls on assumptions about weight
      and shape. CONCLUSIONS: The cognitive content of anorexia nervosa (both
      assumptions and negative self-beliefs) differs from that found in dieting.
      Assumptions about weight and shape may also distinguish dieters from female
      controls.

PMID- 10895365
TI  - Cutaneous vasculitis and cancer: a clinical approach.

PMID- 10895366
TI  - Raloxifene reduces vertebral fracture risk in postmenopausal women with
      osteoporosis.

PMID- 10895367
TI  - Interferon gamma and tumor necrosis factor alpha induce Fas expression and anti
      Fas mediated apoptosis in a salivary ductal cell line.
AB  - BACKGROUND: We previously reported that Fas antigen was strongly expressed on
      salivary duct epithelial cells and that some salivary infiltrating cells showed
      the Fas ligand in patients with severe sialoadenitis due to Sjogren's syndrome
      (SS). Apoptotic changes were observed in ductal epithelial cells and some
      infiltrating cells by DNA nick end labeling methods. These findings suggest that
      the Fas-Fas ligand system may play a role in the pathogenesis of sialoadenitis in
      SS. OBJECTIVE: To elucidate the mechanism of the de novo expression of ductal Fas
      antigen in sialoadenitis associated with SS, we investigated the induction of Fas
      antigen and apoptosis by cytokines in a human salivary duct cell line. METHODS:
      Human salivary duct cell line (HSG) was cultured with interferon gamma (IFN
      gamma), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta),
      interleukin 2 (IL-2), interleukin 4 (IL-4), and granulocyte monocyte colony
      stimulating factor (GM-CSF). The expression of Fas antigen in HSG was examined by
      immunoperoxidase cell ELISA. The appearance of DNA strand breaks during apoptosis
      induced by anti-Fas antibody was detected by DNA nick end labeling methods.
      RESULTS: Unstimulated HSG cells constitutively expressed low levels of Fas
      antigen. IFN-gamma and TNF-alpha consistently upregulated constitutive levels of
      Fas. In contrast, IL-1 beta, IL-2, IL-4, and GM-CSF had no effect on Fas levels.
      HSG cells expressing Fas antigen in response to IFN-gamma or TNF-alpha were
      susceptible to apoptosis by anti-Fas antibody. CONCLUSION: Our findings suggest
      that IFN-gamma or TNF-alpha secreted by infiltrating lymphocytes induces ductal
      Fas expression and ductal apoptosis in sialoadenitis associated with SS.

PMID- 10895368
TI  - Birmingham vasculitis activity score, disease extent index and complement factor
      C3c reflect disease activity best in hepatitis C virus-associated
      cryoglobulinemic vasculitis.
AB  - OBJECTIVE: Clinical measures of vasculitis activity (Birmingham vasculitis
      activity score = BVAS) and disease extent (Disease Extent Index = DEI),
      serological and immunological parameters were evaluated for the monitoring of
      hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV), treated with
      either cyclophosphamide or interferon-alpha 2b depending on disease severity.
      METHODS: Serial serum samples of 15 patients with HCV-associated CV were
      analyzed, and BVAS, DEI, serological and immunological parameters were recorded
      at diagnosis and during therapy. Eight patients were treated with interferon
      alpha 2b and 7 patients with cyclophosphamide. RESULTS: A complete or partial
      response of the CV was seen in both treatment groups. BVAS, complement factor
      C3c, cryoglobulinemia, and rheumatoid factor significantly decreased in both
      treatment groups during 6 months (p < 0.05). DEI decrease was significant in the
      cyclophosphamide group (p < 0.05), and there was a trend in the interferon-alpha
      2b group (p = 0.06). BVAS and DEI were significantly positively correlated, and
      both parameters were significantly negatively correlated with C3c levels in both
      treatment groups (interferon-alpha 2b/cyclophosphamide: r = -0.89, p = 0.001
      versus r = -0.87, p < 0.001, respectively) whereas other parameters were not,
      e.g. ESR and CRP. CONCLUSIONS: Patients with different degrees of disease
      severity, treated with either cyclophosphamide or interferon-alpha 2b depending
      on their disease activity, achieved remission of their CV. BVAS, DEI and C3c were
      especially useful in the follow-up of HCV-associated CV. C3c correlated with BVAS
      and DEI during therapy and provided additional information about vasculitis
      activity that was not reflected by other serological or immunological parameters,
      e.g. ESR or CRP.

PMID- 10895369
TI  - Vertebral bone mineral density changes in female rheumatoid arthritis patients
      treated with low-dose methotrexate.
AB  - OBJECTIVE: To assess vertebral bone mineral density (BMD) changes in rheumatoid
      arthritis (RA) patients taking low-dose methotrexate (MTX). METHODS: We evaluated
      in a 2-year, longitudinal study female RA patients, who had recently started a
      disease-modifying antirheumatic drug (DMARD), divided into two groups: group A,
      receiving MTX, and group B, receiving other DMARDs. Lumbar spine BMD was assessed
      at baseline and every year; RA activity was assessed every 3 months. RESULTS:
      Sixty-two patients were enrolled in the study; 40 completed the follow-up period:
      22 of group A, and 18 of group B. The results after 2 years showed that both
      groups lost bone significantly vs baseline (p < 0.001) in a comparable fashion:
      group A (mean +/- SD) -3.9 +/- 4.9% vs group B -3.0 +/- 3.7% (p = NS). The
      patients who showed active disease lost significantly (p < 0.05) more bone (-5.5
      +/- 3.8%) than those with less active disease (-1.1 +/- 3.6%), independently of
      their DMARD. CONCLUSION: Low-dose MTX in RA does not seem to exert relevant
      effects on trabecular bone.

PMID- 10895370
TI  - IL-1-mediated expression of membrane type matrix-metalloproteinase in rheumatoid
      osteoblasts.
AB  - OBJECTIVE: To determine whether the activation of metalloproteinases can be
      achieved by the interaction of the inflammatory cytokine, IL-1 beta, with
      rheumatoid osteoblasts. RESULTS: MMP-2 is not secreted by rheumatoid osteoblasts
      as a proenzyme; however, IL-1 beta stimulation induced the secretion of MMP-2 as
      an active form from rheumatoid osteoblasts. This MMP-2 activating activity was
      detected significantly in IL-1 beta-stimulated rheumatoid osteoblasts. In support
      of this result, IL-1 beta stimulation induced the expression of membrane type
      matrix-metalloproteinase (MT-MMP), a newly-identified MMP-2 specific activator,
      in rheumatoid osteoblasts. CONCLUSION: These results suggest that IL-1 beta
      induces MMP-2 activation in part by up-regulating MT-MMP expression and
      represents a new mechanism for cytokine-mediated articular destruction in RA.

PMID- 10895371
TI  - Detection of the tax gene of HTLV-I in labial salivary glands from patients with
      Sjogren's syndrome and other diseases of the oral cavity.
AB  - OBJECTIVE: To confirm a possible association between Sjogren's syndrome (SS) and
      the tax gene of human T lymphotropic virus type I (HTLV-I). METHODS: We studied
      by PCR labial salivary glands (LSG) from 50 patients with definite SS and from 58
      controls including 32 patients with LSG involved by other inflammatory processes
      and 26 normal LSG. Antibodies to HTLV-I and antibodies to the Tax protein were
      searched for in serum. RESULTS: We detected the tax gene of HTLV-I in LSG from
      15/50 (30%) of patients with SS but also in specimens from 9/32 (28%) patients
      with LSG involved by other inflammatory processes (3/9 graft-versus-host disease,
      5/19 extra-vasated cysts, 1/4 sarcoidosis) and from only 1/26 (4%) normal LSG. A
      652 bp region, sequenced in 2 SS patients, was 98-98.5% homologous to the canonic
      sequence of tax HTLV-I. The HTLV-I gag, pol and env genes were never detected.
      The serum of the SS patients did not contain antibodies to HTLV-I. However, anti
      Tax antibodies were detected in the serum of 18/25 (72%) SS patients, 10/10
      (100%) patients positive for tax DNA in their LSG and 8/15 (53%) patients
      negative for tax DNA in their LSG. CONCLUSION: Our observations raise the
      possibility that a very low number of copies of the tax gene may be harbored
      innocuously in cells within the oral cavity in some healthy individuals, but that
      this gene may play a role as a co-factor in the development of SS or other
      diseases of oral cavity.

PMID- 10895373
TI  - Serum levels of interleukin-6 and dehydroepiandrosterone sulphate in response to
      either fasting or a ketogenic diet in rheumatoid arthritis patients.
AB  - OBJECTIVE: To investigate the effects of either a 7-day fast or a 7-day ketogenic
      diet upon serum interleukin-6 (IL-6) and dehydroepiandrosterone sulphate (DHEAS)
      in RA patients. METHODS: We measured serum concentrations of DHEAS and IL-6 in 23
      RA patients with active disease, 10 of whom followed a 7-day sub-total fast and
      13 of whom consumed a ketogenic diet (isoenergetic, carbohydrate < 40 g/day) for
      7 days. Clinical and laboratory variables were measured at baseline, on day 7 and
      after re-feeding on day 21. Correlation analyses were used to assess the
      associations between serum IL-6, DHEAS and disease activity variables at each
      timepoint. RESULTS: Fasting, but not the ketogenic diet, decreased serum IL-6
      concentrations by 37% (p < 0.03) and improved disease activity at day 7. Both
      fasting and the ketogenic diet increased serum DHEAS levels by 34% as compared
      with baseline (both p < 0.006). Levels of IL-6, but not DHEAS, correlated with
      several disease activity variables. CONCLUSION: Both fasting and a ketogenic diet
      significantly increased serum DHEAS concentrations in RA patients. Only fasting
      significantly decreased serum IL-6 levels and improved disease activity. As the
      increases in serum DHEAS were similar in response to both fasting and a ketogenic
      diet, it is unlikely that the fall in serum IL-6 or clinical improvements after
      fasting were directly related to increases in serum DHEAS. The fasting-induced
      fall in serum IL-6 may underlie the fall in CRP and ESR observed in RA patients
      in response to a 7-day fast.

PMID- 10895372
TI  - A double-blind placebo-controlled trial of antioxidant therapy in limited
      cutaneous systemic sclerosis.
AB  - OBJECTIVE: To evaluate the effects of a combination of micronutrient antioxidants
      (selenium, beta-carotene, vitamin C, vitamin E and methionine) with allopurinol
      in patients with limited cutaneous systemic sclerosis (SSc). METHODS: The study
      was designed as a placebo-controlled double-blind crossover study. A carryover
      effect was detected retrospectively for some of the prescribed antioxidants, and
      so the data were analysed as: (a) a between group comparison of the first 10 week
      treatment period; and (b) a within group comparison of the first and second 10
      week periods in those who received placebo treatment first. Study end-points were
      plasma von Willebrand factor (vWF), thermographic response to a standard cold
      challenge, frequency and duration of Raynaud's attacks, patient opinion, and
      specialised biochemical parameters (fatty acid profiles, antioxidants and markers
      of free radical injury). RESULTS: Thirty-three patients were recruited. The
      median duration of Raynaud's phenomenon was 10 years (range 2 to 50 years) in the
      active-first group and 10 years (range 4 to 53 years) in the placebo-first group.
      In the 10-week study, there were no differences between the active and placebo
      groups in the change from baseline for vWF, for the parameters of the rewarming
      curve, or for patients' symptoms. Despite a rise in circulating antioxidant
      levels, there was no fall in markers of free radical mediated injury. In the 20
      week cross-over study, patients did not experience any clinical benefit from
      active treatment compared to placebo. CONCLUSION: No clinical benefit could be
      demonstrated from active treatment. There are several possible explanations for
      this negative result, including the short duration of therapy. It is possible
      that antioxidant therapy, to be effective, needs to be given early in the SSc
      disease process, before the onset of irreversible tissue damage.

PMID- 10895375
TI  - Insufficiency fractures in rheumatic patients: misdiagnosis and underlying
      characteristics.
AB  - OBJECTIVE: To report 9 patients with rheumatic diseases referred to our
      observation due to presumed exacerbation of their rheumatic disease, subsequently
      diagnosed as stress insufficiency fractures, and to characterize the clinical
      profile of patients prone to this complication. METHODS: The medical history of
      the patients was reviewed with special emphasis on their rheumatic disease, its
      course, duration and management, their menopausal state, location and
      characteristics of the fracture, its presentation and the initial presumed
      diagnosis, the delay in diagnosis, imaging diagnostic tests performed and
      outcome. Three representative case reports are presented. RESULTS: All 9 patients
      were women, 8 of them aged 50 years old or more, 8 with rheumatoid arthritis and
      1 with polymyalgia rheumatica. They were all treated with corticosteroids and had
      reduction in their bone mass density when evaluated. Three of the patients
      presented with subcapital fracture of the femur, 4 had fractures of metatarsal
      bones and 2 had fractures of the distal tibia. In only one patient was a stress
      fracture initially suspected. Diagnosis was delayed by a mean of 31 days.
      CONCLUSION: The diagnosis of stress fractures in patients with rheumatic diseases
      may often be delayed or missed, and thus improperly treated. Increased awareness
      of this entity is of importance for prompt diagnosis and correct management.

PMID- 10895374
TI  - Safety of disease modifying anti-rheumatic agents in rheumatoid arthritis
      patients with chronic viral hepatitis.
AB  - OBJECTIVE: To examine the safety of the use of disease modifying anti-rheumatic
      drugs (DMARDs) in rheumatoid arthritis (RA) patients with chronic viral hepatitis
      (CVH). METHODS: Records of 600 Chinese patients satisfying the ARA criteria for
      RA in two rheumatology centers were reviewed. Patients with CVH were studied.
      Liver enzymes were checked before (baseline) and during DMARD use at 3-month
      intervals or more frequently if necessary. Drug-episodes (D-Ep), defined as the
      continuous use of DMARD, singly or in combination, for more than 6 months in a
      patient, were analysed. Changes in serum liver alanine transaminase (ALT) levels
      as multiples of the upper range of normal were taken to reflect the severity of
      hepatotoxicity. Changes of ALT to > or = 1.5 times the upper range of normal if
      they were measured at baseline or > or = 2 times the upper range of normal if
      they were measured during and after the use of DMARD were considered as abnormal.
      Control patients included those with CVH alone (n = 623) or RA without CVH (n =
      62) matched for age, sex and D-Ep. RESULTS: 30 RA patients were found to have
      concomitant CVH. One patient was excluded because of use of NSAID alone (n = 1).
      Among the 29 patients, 23 were HBsAg +ve and 6 were anti-HCV Ab +ve. A total of
      47 D-Ep were analysed. 20/47 (42.6%) of D-Ep in 16/29 (55.2%) RA + CVH patients
      developed abnormal ALT levels after a mean 1.9-year duration of DMARD use. This
      was statistically significant when compared with 13/94 (13.8%) of D-Ep which
      ended with abnormal ALT levels in 13/62 (21%) patients with RA alone (p < 0.0001
      for D-Ep which ended up with abnormal ALT, and p < 0.02 for the number of
      patients who developed abnormal ALT) and 128/623 (20.5%) patients with CVH alone
      (p < 0.005). 53% (9/17) of hydroxychloroquine (HCQ) D-Ep were associated with an
      abnormal outcome. Corresponding figures for sulphasalazine (SAZP) and oral or
      intramuscular gold preparations were 55.6% (5/9) and 0% (0/3) respectively. Two
      patients on methotrexate, used either singly or in combination, had normal ALT
      levels throughout the study period. One patient on azathioprine developed
      reactivation of hepatitis B infection. When D-Ep of the RA + CVH group were
      further analysed, 16/43 (37.2%) and 4/4 (100%) D-Ep which started with normal and
      abnormal baseline ALT respectively developed further liver enzyme derangement.
      CONCLUSION: The use of DMARD in RA + CVH patients is associated with a high
      incidence of hepatotoxicity. The effect is likely to be synergistic. This
      includes drugs such as HCQ, which is generally believed to be less hepatotoxic.

PMID- 10895376
TI  - Palindromic rheumatism: effect of dietary manipulation.
AB  - OBJECTIVE: Evaluation of the contribution of dietary components in triggering the
      attacks of palindromic rheumatism (PR), and the effect of dietary manipulation on
      the frequency and severity of PR attacks. METHODS: Sixteen patients (10 males, 6
      females) were diagnosed as having PR during 1994-8 in one center. Their mean age
      was 45 +/- 6, duration of symptoms prior to diagnosis was 4 +/- 1.4 years, and
      frequency of PR attacks were 3.1 +/- 1.8/month. All patients were instructed to
      make a list of the food that was consumed daily and to specify the dates of PR
      episodes. Data were evaluated after a period of 2-4 months in each patient.
      RESULTS: In 5 patients (31%) there was an association between episodes of PR and
      certain foods that were consumed within 36 hours prior to PR episodes. These were
      fish (2 patients), eggs, canned vegetables and processed cheese (each in one
      case). Elimination of the relevant food from each patient's diet resulted in
      complete cessation of the PR attacks in two of the cases, while the other three
      had milder, infrequent attacks. Four patients were rechallenged with the
      offending food. In all cases it resulted in recurrence of the PR attacks. No
      association between PR episodes and prior consumption of certain foods could be
      documented in the other 11 patients. CONCLUSIONS: In some PR patients ingestion
      of certain foods, specific for each case, can trigger the typical attack. It is
      suggested that this association should be looked for in any PR patient, as
      elimination of the offending food from the diet may help in preventing the PR
      attacks.

PMID- 10895377
TI  - Is 99mTc human immunoglobulin G scintigraphy (HIG-scan) useful for the detection
      of spinal inflammation in ankylosing spondylitis?
AB  - OBJECTIVE: To determine the effectiveness of technetium-99m labelled polyclonal
      human immunoglobulin G (HIG-scan) scintigraphy to detect spinal inflammation in
      patients with ankylosing spondylitis. METHODS: Six ankylosing spondylitis (AS)
      patients with inflammatory axial pain and 3 spinal osteoarthritis (OA) patients
      with mechanical axial pain underwent an HMDP scan and an HIG-scan. RESULTS: In
      both AS and spinal OA patients complaining of axial back pain, mechanical and
      inflammatory axial pain, bone scintigraphy revealed foci of markedly increased
      tracer accumulation. An HIG-scan of the region of increased uptake on bone
      scintigraphy did not reveal increased tracer accumulation in either group of
      patients. CONCLUSION: The data suggest that the HIG-scan is not useful in
      detecting inflammatory spinal lesions in ankylosing spondylitis.

PMID- 10895378
TI  - Musculoskeletal infections in intravenous drug addicts: report of 34 cases with
      analysis of microbiological aspects and pathogenic mechanisms.
AB  - OBJECTIVE: To analyse characteristics of musculoskeletal infections in Spanish
      intravenous (i.v.) drug addicts. METHODS: A retrospective analysis of 34 medical
      records was carried out and the aetiologic agent was confirmed in all cases.
      RESULTS: The mean age was 26 years and the sex ratio was 25M/9F. Twenty-four
      patients were HIV-positive and 10 HIV-negative. There were no differences between
      the 2 subgroups. Septic arthritis, seen in 27 cases (79%), was the most common
      type of infection. Axial involvement was present in 23 cases (67%). The organisms
      isolated included Staphylococcus aureus (25 cases), Candida albicans (3 cases),
      Mycobacterium tuberculosis (2 cases), and Neisseria gonorrhoeae, Salmonella
      typhi, Staphylococcus epidermidis and Streptococcus pyogenes in one case each.
      Candida albicans affected the sternocostal joints. Laboratory data showed non
      specific findings. The outcome was mostly good and only one patient died.
      CONCLUSION: Human immunodeficiency virus does not affect characteristics of
      musculoskeletal infections in i.v. drug addicts. Staphylococcus aureus is the
      most frequently isolated pathogen in this population.

PMID- 10895379
TI  - Prediction of 20-year outcome at onset of seropositive rheumatoid arthritis.
AB  - OBJECTIVE: With the advent of new and expensive antirheumatic treatments with
      potentially serious side effects, it would be essential to identify as early as
      possible those rheumatoid arthritis (RA) patients who have a poor prognosis. Here
      study was made of the prognostic value of different markers recorded at the onset
      of RA. METHODS: At the 20-year follow-up of our prospective study, 66 patients
      had rheumatoid factor-positive (RF+) RA. At commencement of follow-up (disease
      duration < 6 months), the prognostic value of 19 demographic, laboratory,
      clinical and radiographic variables was tested to explain the 20-year Larsen
      score for peripheral joints and the Health Assessment Questionnaire (HAQ) index
      using Somers'd for asymmetrical associations. RESULTS: An association was
      observed between onset blood platelets (0.17), serum IgG (0.18), the onset Larsen
      score (0.33) and the 20-year Larsen score. Old age (0.30), serum orosomucoid
      (0.17), the function score (0.28), morning stiffness (0.28), and grip strength
      (0.24) were associated with the 20-year HAQ. CONCLUSION: The correlation between
      the investigated entry variables and end-point outcome was poor. In our
      discussion we conclude that the most important prognostic factor in RF + RA is
      the treatment.

PMID- 10895380
TI  - RANTES gene polymorphism in polymyalgia rheumatica, giant cell arteritis and
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether a biallelic polymorphism (A or G) occurring
      within the promoter region of the RANTES gene (position-403) is associated with
      polymyalgia rheumatica (PMR), giant cell arteritis (GCA) and rheumatoid arthritis
      (RA). METHODS: A PCR-RFLP method was used to genotype cases and controls for this
      polymorphism. 3 groups of patients were examined; these comprised GCA patients
      who did not exhibit features of PMR (n = 30), PMR patients who did not exhibit
      features of GCA (n = 53) and RA patients (n = 99). All patients and controls (n =
      65) originated from the area surrounding Lugo, Galicia, NW Spain. RESULTS: A
      significant increase in the frequency of allele A was found in PMR patients
      compared with normal controls. A marginal increase of this allele frequency was
      observed in RA but not in GCA patients. CONCLUSION: This is the first report of
      an association of a RANTES gene polymorphisms with PMR and RA. Our data suggest a
      possible role for of RANTES in the development of both PMR and RA.

PMID- 10895381
TI  - Reiter's syndrome caused by Streptococcus viridans in a patient with HLA-B27
      antigen.
AB  - A 26-year-old male patient with mitral valve prolapse and HLA-B27 antigen
      received endodontic treatment for dental caries. Two weeks later fever, dysuria,
      diarrhea, sterile inflammatory arthritis of lower limbs, enthesitis, dactylitis,
      conjunctivitis, and uveitis consecutively developed. Blood culture performed at
      the time of active arthritis yielded Streptococcus viridans. He did not have any
      history of psoriasis, acute infectious diarrhea, chronic inflammatory bowel
      diseases, or sexually transmitted diseases. Laboratory studies also excluded the
      possibility of infections by human immunodeficiency virus, hepatitis B or C
      virus, chlamydia, and streptococci from the upper airway. This report indicates
      that Streptococcus viridans can be the triggering microorganisms of Reiter's
      syndrome in some circumstances.

PMID- 10895382
TI  - Pachymeningitis in microscopic polyangiitis (MPA): a case report and a review of
      central nervous system involvement in MPA.
AB  - A case of microscopic polyangiitis (MPA) with pachymeningitis is described. The
      patient had renal, skin, gallbladder and peripheral nervous system involvement,
      simultaneously with pachymeningitis. Necrotizing glomerulonephritis with crescent
      formation, and necrotizing small vessel vasculitis in the kidney and skin were
      confirmed by biopsy. A highly elevated titer of antineutrophil cytoplasmic
      antibody for myeloperoxidase (MPO-ANCA) was observed. All of the clinical and
      laboratory abnormalities improved with high-dose pulse and conventional steroid
      therapy. The literature on central nervous system involvement in MPA and
      perinuclear-ANCA (p-ANCA)-related vasculitis is reviewed. This case serves to
      emphasize that pachymeningitis can occur as one of the features of MPA.

PMID- 10895383
TI  - Sarcoidosis presenting with large vessel vasculitis and osteosclerosis-related
      bone and joint pain.
AB  - A 34-year-old African-American female diagnosed earlier with idiopathic
      thrombocytopenic purpura (ITP), lymphadenopathy, splenomegaly, uveitis, and
      pulmonary nodules, developed a subclavian artery aneurysm, and generalized
      annular osteosclerotic lesions with disabling arthralgias. Biopsies from bone and
      lymph node revealed non-caseating granulomas and no evidence of malignancy or
      infection, confirming the clinical impression of sarcoidosis.

PMID- 10895384
TI  - Use of intravenous immunoglobulin in livedo vasculitis.
AB  - We describe a 36-year-old woman with livedo vasculitis (atrophie blanche) lasting
      for 15 years. After the failure of numerous therapeutic modalities the patient
      was treated with intravenous immunoglobulin. Significant resolution of the
      cutaneous lesions was seen with a concomitant alleviation of pain. To the best of
      our knowledge this is the first patient with livedo vasculitis described in the
      medical literature ever to be treated with IVIG and to achieve a successful
      outcome.

PMID- 10895385
TI  - Evidence-based medicine in pediatric rheumatology.
AB  - Evidence-based medicine (EBM) has increasingly gained importance over the past
      two decades. This review defines and discusses EBM in the light of specific
      issues relating to pediatrics and pediatric rheumatology. The efforts of
      pediatric rheumatologists to practice and promote EBM are summarized.

PMID- 10895386
TI  - Fibromyalgia syndrome: experience in a pediatric rheumatology clinic.
AB  - OBJECTIVE: To report our experience of fibromyalgia syndrome (FMS) in pediatric
      rheumatology clinic settings. METHODS: Clinical and laboratory data were reviewed
      in all patients with FMS between March 1992 and March 1996. Patients with FMS and
      an underlying rheumatic disease were excluded from the study. At presentation and
      follow-up visits, all patients had a tender points (TP) count that was conducted
      by thumb palpation. Both the children and their parents were questioned
      concerning the presence of widespread pain or aching. All the patients fulfilled
      the ACR criteria for the diagnosis of primary FMS. All children were evaluated by
      a protocol that included relevant information on FMS. Telephone survey
      questionnaires were used for patients who missed some of their follow-up visits.
      RESULTS: There were 59 children (47 F and 12 M) diagnosed with primary FMS. The
      mean age at onset was 13.7 years, and the mean age at diagnosis was 15.5 years.
      The mean duration of follow-up was 18.3 months. Diffuse aching was reported in 57
      patients (97%), headaches in 45 (76%), and sleep disturbances in 41 (69%). Less
      common were stiffness in 17 (29%), subjective joint swelling in 14 (24%), fatigue
      in 12 (20%), abdominal pain in 10 (17%), and joint hypermobility and depression
      in 8 (14%) and 4 (7%) patients, respectively. The mean ESR was 15 mm/h, RF was
      negative in all patients, and ANA was positive (mean titer 1:160) in 17 patients.
      The mean initial TP count was 14.6. Nine patients were not available for follow
      up. There were 50 patients available for follow-up and survey analysis, and of
      these 30 (60%) had improved, while 18 (36%) remained unchanged, and 2 (4%) became
      worse when compared with initial presentation. At the end of study follow-up, 37
      patients (74%) were still taking medication (20 of them daily). Out of 25
      patients whose TP counts were available at the end of follow-up, the mean TP
      dropped from 14.12 to 12.04 (p = 0.09) for the total group, and 14.05 to 10.84 (p
      < 0.01) for the patients who had improved. 22 out of 30 patients in the improved
      group and 7 out of 20 in the unchanged or worse group had continued active
      exercise programs (p < 0.001). CONCLUSION: The clinical spectrum of FMS in
      children is similar to that of adults but with better outcomes. The TP count
      correlates with clinical status only in patients who had improved. Active
      exercise programs seem to correlate with better outcomes. Prospective and larger
      patient population studies, and a longer follow-up of children with FMS are
      needed to clarify these findings.

PMID- 10895387
TI  - CYP17 polymorphisms and androgen levels in postmenopausal patients with
      rheumatoid arthritis.

PMID- 10895388
TI  - Headache in SLE.

PMID- 10895390
TI  - HLA-DR shared epitope in familial cases of Japanese rheumatoid arthritis.

PMID- 10895389
TI  - A retrospective evaluation of the treatment of 7 patients with Churg-Strauss
      syndrome.

PMID- 10895391
TI  - Results of a multi-national survey regarding a feasibility study for a
      therapeutic trial in juvenile systemic sclerosis.

PMID- 10895392
TI  - Tolerance of parenteral, higher dose methotrexate in children with juvenile
      chronic arthritis.

PMID- 10895393
TI  - Visual recovery after retinal stroke due to giant cell arteritis.

PMID- 10895394
TI  - A case of Bartter's syndrome, gout and Becker's muscular dystrophy.

PMID- 10895395
TI  - New antiepileptic drugs in children: which ones for which seizures?
AB  - Until 1993, carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), and
      valproate (VPA) accounted for the great majority of the prescriptions written for
      the treatment of epilepsy. Since 1993, five antiepileptic drugs (AEDs) have been
      released in the United States, and at least three additional drugs are expected
      to be released by the end of the year 2000. As a group, these newer drugs differ
      from the established drugs in terms of their pharmacokinetics, interaction
      potential, and adverse effects. In addition, any one of the newer drugs may
      achieve seizure control in situations in which an established drug had not. The
      newer drugs certainly represent a welcome addition to the existing options for
      the treatment of epilepsy in children. However, the availability of several new
      AEDs represents a therapeutic dilemma for the clinician because optimal use of
      these drugs has not yet been established. This is particularly true in children
      because (i) newer drugs are often studied less frequently in children, (ii)
      pharmacokinetics in children differ from those in adults, (iii) children may have
      different adverse effects, and (iv) children have a broader spectrum of various
      seizure types and epilepsy syndromes. In the first part of this review, the
      clinical pharmacology of the currently available newer AEDs is discussed
      individually, with special emphasis on data in children. In particular,
      pharmacokinetics, interactions, dosage and titration, efficacy spectrum, and
      adverse effect profile is discussed for each drug. In the second part, an attempt
      is made to determine the place for the newer drugs in the treatment of the
      different pediatric seizures and epilepsy syndromes.

PMID- 10895396
TI  - Transdermal administration of piribedil reverses MPTP-induced motor deficits in
      the common marmoset.
AB  - The ability of transdermal administration of the dopamine D2/D3 agonist piribedil
      (1-[3,4-methylenedioxybenzyl)]-4-[(2-pyrimidinyl)]piperazine) to reverse
      hypokinesia and other motor deficits observed in MPTP-treated common marmosets
      was investigated. Piribedil (2.5-10.0 mg/animal), applied directly to the skin of
      the abdomen as a paste, produced a long-lasting and concentration-dependent
      reversal of motor deficits. The antiparkinsonian actions of piribedil occurred
      within 10 minutes of drug administration and lasted as long as 10 hours.
      Transdermally applied piribedil produced a pattern of locomotor activity
      characteristic of normal motor behavior in this species. Symptoms of nausea
      (marked excessive salivation, retching, and/or vomiting) were not observed after
      transdermal application of piribedil. Additionally, pretreatment with the
      peripheral dopamine antagonist domperidone enhanced the antiparkinsonian effects
      of piribedil. Application to the skin of monolayer or bilayer patches impregnated
      with piribedil also produced a marked increase in locomotor activity and reversal
      of motor deficits. After application of various patch fractions (whole, one-half,
      or one-fourth), the increase in locomotor activity and reversal of disability
      correlated well with the surface area of skin covered. Measurement of serum
      levels of piribedil after single application of bilayer patches showed a positive
      relationship between drug levels and antiparkinsonian activity. Repeated daily
      application of piribedil bilayer patches for 5 days to MPTP-treated common
      marmosets primed to show dyskinesia by previous exposure to L-Dopa produced
      antiparkinsonian activity accompanied by dyskinetic movements. Transdermal
      administration of dopamine agonists such as piribedil may provide a useful means
      of producing a long-lasting reversal of motor deficits in Parkinson's disease
      while avoiding acute adverse effects such as nausea.

PMID- 10895397
TI  - The relationship between COMT genotype and the clinical effectiveness of
      tolcapone, a COMT inhibitor, in patients with Parkinson's disease.
AB  - Patients with Parkinson's Disease (PD) have a variable response to tolcapone, a
      catechol-O-methyltransferase (COMT) inhibitor. In addition, a subset of patients
      develop severe diarrhea as a side effect. Two codominant alleles for the COMT
      gene exist, coding for low and high activity, resulting in low-, medium-, and
      high-activity genotypes. This study investigates the relationship between this
      variation in genotype and clinical effects in patients with PD taking tolcapone.
      To investigate the relationship between COMT polymorphism and clinical response,
      24 patients who completed tolcapone clinical trials provided blood samples for
      COMT genotype analysis. Change in levodopa dose and United Parkinson Disease
      Rating Scale (UPDRS) Part III (motor subscale) were analyzed at baseline, at 1-2
      weeks, and 6 months after initiation of tolcapone. Genotype analysis was
      performed on seven patients who had diarrhea as a side effect. There was no
      significant correlation between genotype and improvement in UPDRS score (p =
      0.29) according to a linear models approach that adjusted for the subject's
      severity of PD, tolcapone dose (either 100 or 200 mg three times daily) and
      initial differences in baseline scores. No significant difference was seen in
      change in daily levodopa intake and genotype. There was also no relation between
      diarrhea and COMT genotype. These results indicate that, in the treatment of
      Parkinson's disease, COMT genotype is not a major contributor to the clinical
      response to tolcapone.

PMID- 10895398
TI  - Evaluation of the abuse liability of modafinil and other drugs for excessive
      daytime sleepiness associated with narcolepsy.
AB  - Psychostimulants have been used routinely for the treatment of the disabling
      daytime sleepiness associated with narcolepsy. However, the perceived and real
      potential for abuse of amphetamine and amphetaminelike stimulants prompted a
      search for new wake-promoting compounds with lower dependency and abuse
      liabilities. Modafinil is a novel wake-promoting agent with a mechanism of action
      that differs markedly from that of amphetamine and amphetamine-like stimulants.
      In controlled clinical trials, modafinil has been shown to be an effective and
      well-tolerated treatment for excessive daytime sleepiness (EDS) in patients with
      narcolepsy. With a benzhydrylsulfinylacetamide structure, modafinil has a low
      level of solubility in water (< 1 mg/mL) and is unstable at temperatures > or =
      180 degrees C, physicochemical properties that reduce the potential for its abuse
      via intravenous injection and smoking, respectively. Available preclinical and
      clinical data on the abuse liability of modafinil suggest a much lower potential
      for abuse and dependency than amphetaminelike stimulants commonly used for
      treating EDS in patients with narcolepsy. Therefore, modafinil represents a
      valuable therapeutic option for the treatment of EDS associated with narcolepsy.

PMID- 10895399
TI  - An open study of fluvoxamine augmentation of neuroleptics in schizophrenia with
      obsessive and compulsive symptoms.
AB  - Patients whose schizophrenia is characterized by marked obsessive-compulsive
      features can be difficult to treat successfully and often require a combination
      treatment. The aim of this open-label study was to evaluate the efficacy and
      tolerability of an addition of fluvoxamine--a selective serotonin reuptake
      inhibitor (SSRI)--to standard neuroleptics in treatment of obsessive-compulsive
      (OC) symptomatology in patients with schizophrenia. Sixteen patients with
      schizophrenia were treated with conventional neuroleptics and fluvoxamine in
      doses of 100-200 mg/d for 8 weeks. The patients were assessed with use of the
      Brief Psychiatric Rating Scale (BPRS) and the Yale Brown Obsessive-Compulsive
      Scale (YBOCS) at baseline and endpoint. Results included considerable reduction
      in BPRS (39.4%) and Y-BOCS (32.9%) scores. None of the patients showed an acute
      exacerbation during the whole study period. Side effects were clinically
      insignificant. This open-label trial supports previous suggestions that
      coadministration of SSRIs and neuroleptics in patients with schizophrenia with OC
      symptoms is associated with robust improvements of these symptoms. Therefore, the
      use of SSRIs in patients with schizophrenia with OC symptomatology may be
      warranted and safe.

PMID- 10895400
TI  - Beneficial effect of fluoxetine in a case of sporadic hyperekplexia.
AB  - We studied a 67-year-old woman with a sporadic form of hyperekplexia, who
      experienced 8-10 excessive startle responses to unexpected stimuli per month.
      Therapy with fluoxetine had a definite beneficial effect. This finding supports
      the hypothesis that serotonergic mechanisms play a role in this disorder.

PMID- 10895401
TI  - Sertraline-induced panic attacks.
AB  - Sertraline is a selective serotonin reuptake inhibitor that is approved by the
      U.S. Food and Drug Administration for the treatment of major depression,
      obsessive-compulsive disorder (in adults and children), and panic disorder.
      Although numerous studies have found sertraline to be very effective in the
      treatment of anxiety, there have been few case reports of panic attacks actually
      being induced by treatment with sertraline. In this article, we present the cases
      of two patients without any personal or family history of anxiety disorders who
      developed panic attacks shortly after the initiation of sertraline therapy. We
      will also review the literature in regard to the development of anxiety symptoms
      during treatment with the newer antidepressants and discuss the neurochemical
      basis of these antidepressant-induced panic attacks.

PMID- 10895402
TI  - Akathisia and exacerbation of psychopathology: a preliminary report.
AB  - Akathisia has previously been reported to exacerbate psychopathology and to be
      associated with noncompliance, suicidality, and violence. One previous study
      found brisk decrements in psychopathology after acute treatment of akathisia with
      intramuscular biperiden. This study assessed changes in akathisia and
      psychopathology in 19 patients after separate one-day treatments with
      intramuscular benztropine and oral propranolol. Benztropine and propranolol led
      to clinically meaningful and statistically significant decrements in ratings of
      subjective and objective measures of akathisia and in psychopathology scores.
      Changes in psychopathology correlated significantly with changes in subjective
      measures of akathisia after benztropine and with subjective and objective
      measures of akathisia after propranolol. Changes in akathisia accounted for 9%
      42% of the variance in changes in psychopathology. After treatment, statistically
      significant decrements in Brief Psychiatric Rating Scale (BPRS) positive symptoms
      were noted, and individual items not directly related to the akathisia syndrome,
      such as conceptual disorganization, hallucinatory behavior, and unusual thought
      content declined, although not significantly. These findings, taken together with
      the results of a similar previous study, indicate that the effect of akathisia in
      exacerbating psychopathology is large. If suspected, akathisia should be treated
      promptly.

PMID- 10895403
TI  - Is abnormal postprandial lipemia a familial risk factor for coronary artery
      disease in individuals with normal fasting concentrations of triglycerides and
      cholesterol?
AB  - OBJECTIVE: To assess the postprandial response to a fat load in patients with
      coronary artery disease (CAD) and age-matched controls. METHODS: Postprandial
      lipemia was assessed in patients with CAD confirmed by angiography (study group,
      n = 44) and in patients without coronary lesions (control group, n = 20). Family
      members of patients with CAD were also included (spouses group, n = 22; progeny
      group, n = 33). Fasting triglyceride and cholesterol concentrations in the
      control and study groups were less than 2.3 and 6.47 mmol/l, respectively. After
      initial blood sampling, the patients consumed 30% cream (200 ml/m2 body area).
      Repeat measurements of triglycerides, total cholesterol and high-density
      lipoprotein were made after 2, 4, 6, and 8 h. RESULTS: Changes were most marked
      in triglyceride concentrations. Peak values were observed after 4 h in the
      spouses, progeny, and control groups, and after 6 h in the study group. To
      compensate for the large age span (8-40 years) of the progeny, two subgroups were
      formed, taking 25 years as the cut-off value. Triglycerides continued to increase
      until the 4th hour in both subgroups, but the subgroups differed as to the
      absolute concentration of triglycerides. During the first 6 h of the test, the
      concentrations were significantly greater in the subgroup of older progeny than
      in their fathers with CAD. CONCLUSIONS: These findings indicate that
      triglycerides are metabolized at a slower rate and remain longer in the
      circulation of patients with CAD, as compared with patients without CAD. A
      significantly greater level of postprandial lipemia has been observed in adult
      progeny of patients with CAD, suggesting a genetic disorder of triglyceride
      metabolism in these individuals.

PMID- 10895404
TI  - Clandestine ischemia in patients with vasospastic angina.
AB  - BACKGROUND: Coronary vasospasms generally occur at rest, but can also be
      triggered by physical exercise. Anginal pain and ST-segment elevation may be seen
      during exercise-stress tests. ST-segment depression, due to nonocclusive
      vasospasms, has also been found to occur. When the result of a test is positive,
      scintigraphy usually reveals perfusion defects. True silent or clandestine
      ischemia (normal result of exercise test with perfusion defects) in these
      patients is very uncommon. OBJECTIVE: To stress the need for suspecting
      occurrence of coronary vasospasms in order to perform a proper diagnosis.
      METHODS: Eight patients with angina were selected for this study. They had
      negative results of exercise tests with perfusion defects detected by thallium
      201 tomography, normal coronary arteries and vasospasms. Maximal exercise-stress
      tests with thallium-201 tomography were performed. Sizes of perfusion defects
      were quantified by examining polar maps. Coronary angiography and then an
      intracoronary ergonovine test were performed for each patient. RESULTS:
      Significant defects were seen in territory of the right coronary artery, the left
      anterior descending artery, or both. Lung:heart ratio was normal in every case.
      The coronary arteries were normal and vasospasms were elicited with ergonovine in
      all the patients. Correspondence between the location of perfusion defects and
      angiographic spasms was generally observed. After treatment with calcium
      antagonists and nitrates all of them improved and defects detected by thallium
      tomography were no longer found when tests were repeated. CONCLUSIONS: Some
      patients with vasospastic angina may have normal results of exercise-stress tests
      and reversible perfusion defects detectable by scintigraphy. This finding must
      lead one to perform coronary angiography without administration of nitroglycerine
      beforehand and an ergonovine test if the coronary arteries are normal.

PMID- 10895405
TI  - Release of platelet activation markers during coronary angioplasty.
AB  - BACKGROUND: Authors of several studies have reported that activation of platelets
      occurs during coronary angioplasty, but consistent results have not been
      obtained. Levels of serotonin in coronary circulation have been found to be
      elevated during percutaneous transluminal coronary angioplasty but greater than
      normal concentrations of beta-thromboglobulin and platelet factor 4 have not been
      detected. OBJECTIVE: To perform a serial analysis of platelet-activation markers
      with simultaneous measurements of levels of serotonin, beta-thromboglobulin and
      platelet factor 4 in blood samples from the coronary artery and coronary sinus of
      patients undergoing coronary angioplasty. METHODS: Twenty patients undergoing
      elective coronary angioplasty were studied. Measurements of levels of beta
      thromboglobulin, platelet factor 4, and serotonin in samples from the ostium of
      the coronary artery and the coronary sinus were performed immediately before
      angioplasty and after the first balloon deflation. RESULTS: Concentrations of
      beta-thromboglobulin and platelet factor 4 in coronary artery and coronary sinus
      were elevated in all patients before dilatation, whereas concentrations of
      serotonin were elevated in 85% of the patients. Concentrations of all markers in
      coronary sinus decreased after the first inflation. The coronary-sinus: coronary
      artery concentration ratios before dilatation for beta-thromboglobulin, platelet
      factor 4, and serotonin were > 1 for the majority of patients, particularly for
      those with complex culprit lesions, indicating that coronary activation of
      platelets was occurring. Ratios remained unchanged or decreased after the first
      inflation, depending on initial values. CONCLUSIONS: Both systemic and coronary
      activation occur in patients subjected to percutaneous transluminal coronary
      angioplasty before the onset of intervention. After balloon deflation the greater
      than normal baseline coronary-sinus:coronary-artery concentration ratios of all
      markers (beta-thromboglobulin, platelet factor 4 and serotonin) tend to decline
      or remain unchanged, depending on the level of activation.

PMID- 10895406
TI  - Age and sex differences in presentation of symptoms among patients with acute
      coronary disease: the REACT Trial. Rapid Early Action for Coronary Treatment.
AB  - BACKGROUND: There are few data on possible age and sex differences in
      presentation of symptoms for patients with acute coronary disease. OBJECTIVE: To
      investigate demographic differences in presentation of symptoms at the time of
      hospital presentation for acute myocardial infarction (AMI) and unstable angina.
      METHODS: The medical records of patients who presented with chest pain and who
      also had diagnoses of AMI (n = 889) or unstable angina (n = 893) on discharge
      from 43 hospitals were reviewed as part of data collection activities of the
      Rapid Early Action for Coronary Treatment trial based in 10 pair-matched
      communities throughout the USA. RESULTS: Dyspnea (49%), arm pain (46%), sweating
      (35%), and nausea (33%) were commonly reported by men and women of all ages in
      addition to the presenting complaint of chest pain. After we had controlled for
      various characteristics through regression modeling, older persons with AMI were
      significantly less likely than were younger persons to complain of arm pain and
      sweating, and men were significantly less likely to report vomiting than were
      women. Among persons with unstable angina, arm pain and sweating were reported
      significantly less often by elderly patients. Nausea and back, neck, and jaw pain
      were more common complaints of women. CONCLUSIONS: Results of this study suggest
      that there are differences between symptoms at presentation of men and women, and
      those in various age groups, hospitalized with acute coronary disease. Clinicians
      should be aware of these differences when diagnosing and managing patients
      suspected to have coronary heart disease.

PMID- 10895407
TI  - Evaluation of myocardial viability in asymptomatic patients early after
      infarction with perfusion/metabolism single-photon-emission computed tomographic
      imaging and dobutamine echocardiography.
AB  - OBJECTIVE: To study the impact of detection of viability of myocardium in
      asymptomatic patients early (3-10 days) after Q-wave myocardial infarction on
      segmental recovery of left ventricular function after elective revascularization.
      METHODS: Patients were studied with low-dose dobutamine echocardiography (LDDE)
      and single photon-emission computed tomography with 99mTc sestamibi and [18F]
      fluorodeoxyglucose (FDG) imaging. Viability of myocardium was defined as
      detection of improvement in segmental thickening of left ventricle by LDDE
      (versus baseline echocardiographic data), uptake of 99mTc sestamibi > 50% of
      maximum counts, uptake of [18F]-FDG > 50% of maximum normal, combined uptake of
      99mTc sestamibi or [18F]-FDG > 50% of normal maximum, uptake of [18F]-FDG > 50%
      or mismatched pattern (uptake of [18F]-FDG greater than that of 99mTc sestamibi).
      Functional recovery was defined as improvement of segmental thickening of left
      ventricle detected at follow-up 8 weeks after infarction (versus baseline resting
      echocardiographic data). Interpretation of the tests was blinded with respect to
      the angiographic data and the results of the alternative method. RESULTS: In
      total 18 patients with 133 left-ventricle segments with abnormal contractile
      function at baseline were analysed; 29% were hypocontractile and 71% were
      noncontractile. Examination with LDDE showed that 18% of the segments had normal
      contractility and 26% were hypocontractile; the respective percentages were 29
      and 28% according to follow-up resting echocardiography. Radionuclide tests for
      viability of myocardium gave positive results in 57% (uptake of [18F]-FDG > 50%)
      and 62% (uptake of 99mTc sestamibi > 50%) of cases. With respect to segmental
      analysis, there was a 25-27% positive concordance, a 24-27% negative concordance,
      and a 48-50% discordance between the LDDE and the radionuclide definitions of
      viability of myocardium. Additionally, there was no significant difference among
      sensitivities and specificities for the definitions of viability. The sensitivity
      was 69% for the uptake of 99mTc sestamibi > 50% criterion, and the highest
      specificity was 66% for the LDDE. Incorporation of imaging with [18F]-FDG into
      the analysis yielded a marginally higher sensitivity of 71% for the criterion of
      uptake of [18F]-FDG or 99mTc sestamibi > 50%, versus imaging with the 99mTc
      sestamibi alone. CONCLUSION: LDDE was more specific and radionuclide imaging more
      sensitive for detection of viability of myocardium in asymptomatic patients early
      after infarction. Possibly defective myocardial metabolization of glucose in the
      period early after infarction and the specific LDDE protocol applied account for
      the limited benefit of these studies in terms of facilitating prediction of
      segmental functional recovery after revascularization in this clinical setting.

PMID- 10895408
TI  - Value of the initial electrocardiogram in patients with inferior-wall acute
      myocardial infarction for prediction of multivessel coronary artery disease.
AB  - BACKGROUND: Patients with inferior-wall acute myocardial infarction (AMI) who
      have ST-segment depression in the left precordial leads (LSTD+) on the initial
      electrocardiogram were reported to have more diffuse coronary artery disease
      (CAD) than had those without this finding (LSTD-). This suggests that LSTD+
      patients may need extensive revascularization interventions more often than do
      LSTD- patients. However, this has not yet been confirmed. OBJECTIVE: To compare
      the coronary angiographic findings and treatment strategies for patients with
      inferior-wall AMI according to the LSTD pattern. METHODS: The clinical outcomes
      and the angiographic findings for 238 consecutive patients aged < or = 75 years
      who had been admitted to our hospital between 1 February 1995 and 1 February 1997
      with inferior-wall AMI were retrospectively analyzed. The patients were divided
      into two groups according to the pattern of precordial ST-segment depression:
      LSTD+, ST-segment depression in leads V4-V6; and LSTD-, absence of this finding.
      All patients were treated according to current practice guidelines including with
      thrombolysis and revascularization interventions. RESULTS: The final study
      population included 217 patients; 83 were LSTD+ and 134 were LSTD-. All underwent
      coronary angiography within 30 days of the infarction. Compared with LSTD-
      patients, LSTD+ patients tended to be older (mean age 62.7 +/- 11.7 versus 58.3
      +/- 9.6 years, P = 0.004), and had higher incidences of hypertension (39.8 versus
      24.6%, P = 0.019) previous myocardial infarction (45.8 versus 20.1%, P = 0.0001)
      and congestive heart failure (21.7 versus 3.7%, P = 0.00008). Three-vessel CAD
      was much more common, and single-vessel CAD much less common, in the LSTD+ than
      in LSTD- group (62.7 versus 13.4% and 8.4 versus 50.7%, P < 0.00001 for both).
      Coronary-artery-bypass surgery and multivessel percutaneous coronary
      interventions (PCI) were used in treating 65.1% of the LSTD+ versus only 6.0% of
      the LSTD- patients (P < 0.00001), whereas single-vessel PCI was used in treating
      71.6% of the LSTD- patients versus only 24.1% of the LSTD+ patients (P <
      0.00001). Thus, the LSTD- pattern predicted single-vessel disease and single
      vessel PCI only, whereas the LSTD+ pattern was predictive of multivessel CAD and
      of use of coronary-artery-bypass surgery or multivessel PCI (predictive values of
      94.0 and 65.1%, respectively). CONCLUSIONS: Among patients with inferior-wall
      AMI, left precordial ST-segment depression predicts a very high prevalence of
      multivessel CAD and use of extensive revascularization interventions. The absence
      of this finding predicts nondiffuse CAD and lack of a need for extensive
      revascularization.

PMID- 10895409
TI  - Effect of adjunctive intracoronary adenosine on myocardial ischemia, hemodynamic
      function and left ventricular performance during percutaneous transluminal
      coronary angioplasty: clinical access to ischemic preconditioning?
AB  - BACKGROUND: Ischemic preconditioning has been defined as a mechanism that renders
      the heart more resistant to subsequent ischemia. Adenosine plays an important
      role in the pathogenesis of ischemic preconditioning. OBJECTIVE: To assess
      whether intracoronary administration of adenosine prevents the deterioration of
      left ventricular performance and hemodynamic function by allowing adaptation to
      myocardial ischemia in the setting of percutaneous transluminal coronary
      angioplasty (PTCA). DESIGN: This was a prospectively randomized doubly blinded
      trial. METHODS: We investigated 20 patients undergoing PTCA of the left anterior
      descending coronary artery supplying myocardium with normal left ventricular
      function in the setting of stable angina pectoris. Patients were randomly
      allocated to be administered adenosine intracoronarily (20 mg/10 min) or an equal
      amount of saline, providing a control population. Results of standardized chest
      pain questionnaires, tolerated inflation times, ST-segment shifts, left
      ventricular and aortic pressures, isovolumetric phase indexes, and indexes of
      volume and ejection fraction during the course of PTCA between the two groups
      were compared. RESULTS: Patients administered adenosine tolerated significantly
      longer balloon-inflation times (188 +/- 41 versus 153 +/- 36 s; P = 0.03), which
      were associated with less pronounced signs of ischemia, and exhibited less
      deterioration of isovolumetric phase indexes during PTCA. Deterioration of left
      ventricular ejection fraction was slightly less severe with adenosine (72 +/- 5%
      before PTCA versus 64 +/- 6% during angioplasty) than it was for the control
      group (71 +/- 7% before PTCA versus 60 +/- 7% during angioplasty; P = 0.11).
      CONCLUSIONS: Intracoronary application of adenosine prior to coronary angioplasty
      increases tolerance of ischemia and prevents deterioration of left ventricular
      hemodynamics during ischemia. One potential explanation of these results is that
      induction of ischemic preconditioning took place.

PMID- 10895410
TI  - The relative rapidity of recanalization induced by recombinant tissue-type
      plasminogen activator (r-tPA) and TNK-tPA, assessed with enzymatic methods.
AB  - BACKGROUND: Comparison of different plasminogen activators is difficult because
      conventional endpoints such as mortality are relatively insensitive to potential
      differences in efficacy with respect to rapidity of recanalization of infarct
      related arteries. METHODS: This study was performed to determine whether valid
      comparisons could be made by means of biochemical endpoints that have been
      demonstrated previously to permit estimation of the time of opening of an infarct
      related artery in experimental animals and in patients. The method is based on
      time-dependent interconversion of isoforms of creatine kinase mediated by
      carboxypeptidase N, an enzyme present in excess in circulating blood. A small
      subset of 39 patients studied in the ASsessment of the Safety and Efficacy of a
      New Thrombolytic agent (ASSENT-2) trial were evaluated to determine the
      feasibility of using the creatine kinase isoform method for comparison of two
      tissue-type plasminogen activators (tPA), recombinant tPA (r-tPA) and TNK-tPA.
      RESULTS: Early recanalization (within 40 min of the onset of treatment with the
      plasminogen activator) occurred in 56% of patients treated with r-tPA and 76% of
      those treated with TNK-tPA. CONCLUSIONS: Differences in the efficacy of
      plasminogen activators with respect to rapidity of recanalization appear to be
      readily detectable by means of assaying creatine kinase isoforms in serially
      acquired blood samples under conditions that permit widespread application of the
      approach developed.

PMID- 10895412
TI  - Bibliography. Current world literature.

PMID- 10895411
TI  - Risk factors for coronary artery disease in old persons in an academic hospital
      based geriatrics practice.
AB  - BACKGROUND: Risk factors for coronary artery disease (CAD) in old men and women
      include age, cigarette smoking, hypertension, diabetes mellitus, dyslipidemia,
      and obesity. OBJECTIVE: To investigate the association of risk factors with
      prevalence of CAD. METHODS: We performed a retrospective analysis of charts for
      all old persons seen during the period from 1 January 1998 through 15 June 1999
      at an academic hospital-based geriatric practice to investigate associations of
      risk factors with prevalence of CAD among old persons. We studied 467 men, mean
      age 80 +/- 8 years, and 1444 women, mean age 81 +/- 8 years. RESULTS: CAD was
      present in 201 of 467 men (43%) and in 473 of 1444 women (33%; P < 0.0001). Risk
      factors for CAD according to univariate analysis were age (P < 0.0001 for women),
      cigarette smoking (P < 0.0001 for men and women), hypertension (P < 0.0001 for
      men and women), diabetes mellitus (P < 0.0001 for men and women), obesity (P <
      0.0001 for men and women), and serum levels of total cholesterol (P < 0.0001 for
      men and P = 0.0001 for women), low-density lipoprotein (LDL) cholesterol (P <
      0.0001 for men and P = 0.001 for women), and high-density lipoprotein (HDL)
      cholesterol (inverse association; P = 0.0001 for men and women). Stepwise
      logistic regression analysis showed that significant independent risk factors for
      CAD were cigarette smoking (odds ratio 6.7 for men), hypertension (odds ratios
      3.3 for men and 2.7 for women), and serum levels of HDL cholesterol (odds ratio
      0.83 for men and women) and LDL cholesterol (odds ratios 1.10 for men and 1.09
      for women). CONCLUSIONS: Significant independent risk associations with
      prevalence of CAD among old persons were found for cigarette smoking by men,
      hypertension in men and women, and serum levels of HDL cholesterol (inverse
      association) in men and women, and of LDL cholesterol in men and women.

PMID- 10895413
TI  - Selective DNA release from DQAsome/DNA complexes at mitochondria-like membranes.
AB  - The number of diseases found to be associated with defects of the mitochondrial
      genome has grown significantly over the past decade (Wallace 1999). Despite major
      advances in understanding mtDNA defects at the genetic and biochemical level,
      there is no satisfactory treatment available for the vast majority of patients
      and the exploration of gene therapeutic approaches is highly warranted. However,
      mitochondrial gene therapy still appears only theoretical and speculative. Any
      possibility for gene replacement depends on the use of a yet unavailable
      mitochondria-specific transfection vector. Mitochondria-specific vectors must
      posses two properties: they have to transport DNA to the side of mitochondria;
      they must not release DNA during endocytosis. Amphiphile compounds with
      delocalized cationic charge centers such as rhodamine 123 and the bolaamphiphile
      dequalinium have long been known to accumulate in mitochondria. Sufficient
      lipophilicity combined with delocalization of the positive charge to reduce the
      free energy change when moving from an aqueous to a hydrophobic environment are
      believed to be prerequisite for mitochondrial accumulation in response to the
      mitochondrial membrane potential. We have recently succeeded in preparing
      cationic vesicles made of dequalinium that we termed DQAsomes (Weissig et al.
      1998a). We have shown that DQAsomes bind and protect DNA against DNase activity
      (Lasch et al. 1999). Based on the intrinsic property of dequalinium to
      preferentially accumulate in mitochondria in response to the electrochemical
      gradient at the mitochondrial membrane, we believe that DQAsomes can serve as a
      vector to deliver DNA to mitochondria in living cells. As a first step in the
      development of mitochondria-specific DNA delivery systems, we report here that
      DQAsome/DNA complexes selectively release DNA at cardiolipin-rich liposomes
      mimicking both the inner and the outer mitochondrial membrane. We demonstrate
      that DNA remains tightly associated with DQAsomes in the presence of an excess of
      anionic lipids other than cardiolipin.

PMID- 10895414
TI  - Influence of the fluidity of liposome compositions on percutaneous absorption.
AB  - The penetration into the stratum corneum of fluorescein, as the acid form or as a
      sodium salt, encapsulated in liposomes formed by liquid- or gel-state
      phospholipids, with or without cholesterol, was investigated in humans by the
      stripping method. Liposomes prepared by extrusion were applied to the forearms of
      healthy human volunteers and 30 min later, strippings were performed. Fluorescein
      was extracted and determined by spectrofluorimetry. The skin penetration of
      sodium fluorescein was higher from fluid liposomes (phosphatidylcholine) than
      from rigid liposomes (hydrogenated phosphatidylcholine), but it was independent
      of the content of cholesterol. It seems that the liquid-crystalline state of the
      lipids is the main aspect involved in the fluidity of the liposome bilayer itself
      as well as in the interaction with the lipids of the stratum corneum. The similar
      enhanced penetration behavior obtained for unsaturated liposomes containing
      sodium or acid fluorescein seems to support the hypothesis of a previous
      destruction of the vesicles during its passage through the lipid intercellular
      pathway in the stratum corneum.

PMID- 10895415
TI  - A microsphere-liposome (microplex) vector for targeted gene therapy of cancer.
      II. In vivo biodistribution study in a solid tumor model.
AB  - Cationic liposomes are commonly used for transfection of plasmids into mammalian
      cells, while microspheres have been traditionally used for selective delivery of
      anticancer agents into tumor vasculature. We have developed a novel vector,
      comprised of cationic liposomes electrostatically bound to ion-exchange
      microspheres (termed 'microplex') for targeted gene therapy of solid tumors. The
      delivery modes tested in a rat solid tumor model were free plasmids, plasmids
      bound to microspheres, to liposomes, or to the combination vector. The greatest
      amount of chloramphenicol acetyltransferase (CAT) reporter gene expression in
      tumors was achieved using the microplex vector; 3.4-fold compared with free, and
      1.8-fold compared with both microspherical and liposomal deliveries (p < 0.01).
      Tumor-to-normal kidney tissue CAT expression ratios were as follows: free 1.9:1;
      microspherical 3.7:1; liposomal 1.4:1 and microplexical 2.7:1. Expression between
      the two types of tissues was significantly different (p < 0.01) for all delivery
      modes. Microspheres targeted the plasmids to the tumors, while the action of
      cationic liposomes on cellular membranes allowed more plasmids to breach the cell
      membrane. This study has proven that the novel microplex vector is capable of
      selective delivery of genes to tumors and has the potential to target genes in
      clinical trials.

PMID- 10895416
TI  - Modulating blood-brain barrier interactions of amino acid-based anticancer
      agents.
AB  - The large neutral amino acid (LNAA) transporter at the blood-brain barrier (BBB)
      mediates brain uptake of amino acid-based anticancer agents (e.g., melphalan and
      acivicin). In this study, we blocked the amino acid terminus of the anticancer
      agents using a bioreductive drug delivery system (TDDS). This molecular
      modification of the anticancer agents is expected to prevent LNAA carrier
      mediated transport across the BBB. In this study, we demonstrate that the parent
      amino acid containing anticancer agents are substrates for the LNAA transporter
      at the BBB, whereas the TDDS is not recognized by the LNAA transporter. An in
      situ rat brain perfusion technique was used to determine competition for LNAA
      carrier-mediated transport at the BBB using [14C]L-leucine. The BBB capillary
      permeability-surface area (PA) product for the radiotracer [14C]L-leucine
      (control) was determined to be 5.18 +/- 0.32 x 10(-2) ml/s/g (100%). The control
      PA value for [14C]L-leucine was competitively inhibited (down to 7-18% of
      control) by excess L-phenylalanine as well as by excess concentration of the
      anticancer amino acids, melphalan and acivicin, showing competition for the LNAA
      transporter at the BBB. In contrast, brain perfusion of [14C]L-leucine in
      presence of excess TDDS resulted in no competition for brain uptake of [14C]L
      leucine via the LNAA transporter. Thus, bioreversible derivatization of the
      parent anticancer amino acids resulted in blocking the amino acid functional
      group, thereby leading to loss of recognition for the cerebrovascular LNAA
      transporter at the BBB.

PMID- 10895417
TI  - Safety assessment of encapsulated morphine delivered epidurally in a sustained
      release multivesicular liposome preparation in dogs.
AB  - We have shown that the epidural (EPI) delivery of morphine encapsulated in
      multivesicular liposomes (DepoFoam drug delivery system) produces a sustained
      clearance of morphine and a prolonged analgesia. We have sought to subsequently
      determine the likelihood of deleterious effects on local tissue of repetitive
      epidural injections of this encapsulated morphine preparation (C0401). Beagle
      dogs were prepared according to protocol approved by the Institutional Animal
      Care and Use Committee under volatile general anesthesia with chronic lumbar EPI
      catheters and subcutaneous injection ports. Male and female dogs (three groups)
      received a total of 4 EPI injections at 8-day intervals of 3 mL of C0401 (10
      mg/mL morphine) (N = 6), DepoFoam vehicle (N = 6), or 0.9% sodium chloride (N =
      6). Following EPI-C0401, but not saline or DepoFoam vehicle, there were transient
      (< 72 hr) decreases in food consumption, arousal, hindlimb muscle tone, and body
      temperature. Heart rate was unaltered, but there were modest decreases in blood
      pressure and respiratory rate, which persisted for 24-72 hr after C0401. No
      persistent changes in sensory/motor function, body weight, or stool/urine
      production were observed. Cerebrospinal fluid, blood chemistry, and urinalysis
      performed at surgery and on the day of sacrifice (24 hr after the last dose) were
      within normal ranges. Gross pathology at necropsy was unremarkable. Spinal
      histopathology findings were judged to be minimal (e.g., modest pericatheter
      inflammation and fibrosis) and present in all dogs. However, a statistical trend
      in the rank order of pathology scores was noted (Saline < DepoFoam vehicle <
      C0401). Repeated EPI injection of C0401 at the maximum dose that could be
      administered (30 mg) resulted in moderate, transient behavioral and physiological
      effects after each injection, consistent with morphine administration, and a
      modest effect on cord histopathology. This level of pathology is reflected in the
      lack of change observed in cerebrospinal fluid and lack of neurological findings.
      These results suggest that C0401 is without significant pathological effects at
      this dose after repeated epidural delivery in dogs.

PMID- 10895418
TI  - Comparison of the effects of dimyristoyl and soya phosphatidylcholine liposomes
      on human fibroblasts.
AB  - The in vitro effects of prolonged exposure (8 days) of human skin fibroblasts to
      several concentrations of extruded dimyristoyl (dm-PC) and soya
      phosphatidylcholine (soya-PC) liposomes were compared. Prepared liposome
      suspensions were added to the fibroblast culture medium at phospholipid
      concentrations of 10, 50, 100, 200, and 300 microM. Survival curves and values of
      50% inhibitory concentration (IC50) and area under the curve (AUC) were used to
      compare the response of the fibroblasts to the two types of liposomes. The effect
      of the incorporation of vitamin E in the liposomal preparations also was
      determined. Fibroblasts showed greater sensitivity toward the soya-PC liposomes
      (IC50 = 150 microM) than the dm-PC liposomes (IC50 = 212 microM). The presence of
      vitamin E in the soya-PC liposomes led to a 1.9-fold increase in the IC50, while
      dm-PC liposomes containing vitamin E showed an IC50 that was 1.1 times higher
      than that shown by control vitamin-free liposomes. Soya-PC liposomes containing
      vitamin E at a molar ratio of 10:0.5 (phospholipid:vitamin) were best tolerated
      by the fibroblasts (IC50 > 300 microM). It would appear that dm-PC liposomes are
      better tolerated by fibroblasts than those composed of soya-PC. However, the
      incorporation of vitamin E into the liposomes seems to reverse this effect, and
      it is the vitamin-containing soya-PC liposomes that are most compatible with the
      growth of fibroblasts in culture.

PMID- 10895419
TI  - A calorimetric study on diflunisal release from poly(lactide-co-glycolide)
      microspheres by monitoring the drug effect on dipalmitoylphosphatidylcholine
      liposomes: temperature and drug loading influence.
AB  - Diflunisal release from poly-Lactide-co-Glycolide (50:50, 34,000 MW) microspheres
      loaded with two different amounts of drug (2.5 +/- 0.5% and 10 +/- 0.5% w/w) was
      monitored by following the effects exerted by the drug on the thermotropic
      behavior of dipalmitoylphosphatidylcholine unilamellar vesicles at different
      temperatures. The effects of the drug released from the microspheres on the
      thermotropic behavior of lipid aqueous dispersion containing different molar
      ratios of drug was detected by differential scanning calorimetry and was compared
      with the effects exerted by the free Diflunisal. Diflunisal affects mainly the
      temperature (Tm) of the transition characteristic of phospholipid vesicles as
      model biomembrane, causing a shift toward lower values. This shift was modulated
      by the drug molar fraction with respect to the lipid concentration in the aqueous
      dispersion. Afterward, calorimetric measurements were performed on suspensions of
      blank liposomes added to weighed amounts of unloaded and differently Diflunisal
      loaded microspheres as well as free powdered Diflunisal after incubation for
      increasing times at three different temperatures (25, 37, and 50 degrees C). The
      Tm shifts of the lipid bilayer, caused by the drug released from polymeric system
      as well as by the free drug during incubation periods, were compared with that
      caused by free drug increasing molar fractions dispersed directly on the
      membrane, employed as a calibration curve to obtain the fraction of drug
      released. This in vitro study suggests that the kinetic process involved in drug
      release is influenced by the amount of drug loaded in the microspheres as well as
      by the temperature acting on drug solubility and membrane disorder. This drug
      release model, monitored by the calorimetric technique shows that a) the poly
      Lactide-co-Glycolide microspheres are a good delivery system able to sustain the
      drug release; b) the differential scanning calorimetry technique applied on the
      drug interaction with biomembranes constitutes a good tool to follow the drug
      release; 3) this model, representing an innovative alternative in vitro model,
      should be used to determine the different kinetics involved in the drug transfer
      from a drug delivery system to a membrane as uptake site.

PMID- 10895420
TI  - Advantages of low output mobile communication systems in hospitals.
AB  - Mobile telephone systems using radio waves with very low power outputs rarely
      interfere with electronic medical equipment, which allows them to be safely
      installed in hospitals. The Personal Handy-phone System, PHS, which was developed
      and is widely used in Japan, is one such system. It has many useful functions
      including voice communication, string message transfer, e-mail, an answering
      system limited to selected persons or groups, paging, automatic call transfer,
      and handset positioning. In this paper we discuss the benefits of these functions
      confer to hospital communication systems.

PMID- 10895421
TI  - A proposed scheduling model to improve use of computed tomography facilities.
AB  - A nonpreemptive queuing system based upon operations management theory is used to
      evaluate expected steady state wait periods for traditional and distributed CT
      scheduling models. Both models are constructed using two classes of patient
      service--emergent and nonemergent. The former model uses only one point of
      service per scanner while the latter employs multiple points of service in order
      to accomplish all of the functions necessary to complete a CT scan. Sample data
      are drawn from a tertiary care hospital-based system using a traditional service
      model. Comparison of a traditional and distributed service system, each with
      emergent and nonemergent service classes, shows that breaking as many activities
      as possible out of the scanner should provide substantial improvements in cost
      efficiency and service for patients having CT scans. Nonemergent patients may
      experience as much as an 89% reduction in steady-state wait times while emergent
      patients may experience as much as a 59% reduction in wait times. The cost
      efficiencies recognized either through increased scanner utilization or reduced
      scanner needs, even with only modest improvements, should more than offset any
      additional personnel needed to implement a distributed model. Proper
      implementation of a distributed scheduling model for CT scanning can provide
      substantial cost efficiencies and improvements in service for both nonemergent
      and emergent CT scans.

PMID- 10895422
TI  - Extending simulation modeling to activity-based costing for clinical procedures.
AB  - A simulation model was developed to measure costs in an Emergency Department
      setting for patients presenting with possible cervical-spine injury who needed
      radiological imaging. Simulation, a tool widely used to account for process
      variability but typically focused on utilization and throughput analysis, is
      being introduced here as a realistic means to perform an activity-based-costing
      (ABC) analysis, because traditional ABC methods have difficulty coping with
      process variation in healthcare. Though the study model has a very specific
      application, it can be generalized to other settings simply by changing the input
      parameters. In essence, simulation was found to be an accurate and viable means
      to conduct an ABC analysis; in fact, the output provides more complete
      information than could be achieved through other conventional analyses, which
      gives management more leverage with which to negotiate contractual
      reimbursements.

PMID- 10895423
TI  - Design of low-cost general purpose microcontroller based neuromuscular
      stimulator.
AB  - In this study, a general purpose, low-cost, programmable, portable and high
      performance stimulator is designed and implemented. For this purpose, a
      microcontroller is used in the design of the stimulator. The duty cycle and
      amplitude of the designed system can be controlled using a keyboard. The
      performance test of the system has shown that the results are reliable. The
      overall system can be used as the neuromuscular stimulator under safe conditions.

PMID- 10895425
TI  - Control of dental prosthesis system with microcontroller.
AB  - In this study, a microcontroller-based electronic circuit was designed and
      implemented for dental prosthesis curing system. Heater, compressor and valve
      were controlled by 8-bit PIC16C64 microcontroller which is programmed using MPASM
      package. The temperature and time were controlled automatically by preset values
      which were inputted from keyboard while the pressure was kept constant.
      Calibration was controlled and the working range was tested. The test results
      showed that the system provided a good performance.

PMID- 10895424
TI  - Regional variation in physician practice pattern: an examination of technical and
      cost efficiency for treating sinusitis.
AB  - OBJECTIVE: An examination of the physician efficiency and resulting cost patterns
      by region. DATA SOURCES: Virginia Medicaid sinusitis related claims for 1993 were
      aggregated to physician level (n = 178), and Area Resources File for 1993 was
      used to identify regions for evaluation. STUDY DESIGN: The best practice
      performance in the usage of five resources (i.e., primary care physician visits,
      referral services, emergency room visits, prescriptions, laboratory tests) was
      identified using Data Envelopment Analysis (DEA). Five regions in Virginia were
      identified according to regional planning to evaluate the variation in efficiency
      across these regions. PRINCIPAL FINDINGS: Inefficient physicians consumed
      significantly more resources and were 48% more costly than efficient physicians.
      Substantial regional variation was found and mainly attributed to the differences
      in use of prescriptions and laboratory procedures. Urban-rural discrepancy may
      explain part of the variation. CONCLUSIONS: As this study reveals the existence
      of substantial variation in physician efficiency, actions should be taken to
      minimize the variation that is more affected by personal and structural factors.
      For example, information on efficient use of resources and corresponding patient
      outcomes can be disseminated to the attending physicians. Educational workshops
      can be conducted to allow sharing of experience between efficient and inefficient
      physicians. Efforts should also be directed to help inefficient physicians to
      adhere to practice guidelines.

PMID- 10895426
TI  - Remote control of microcontroller-based infant stimulating system.
AB  - In this paper, a remote-controlled and microcontroller-based cradle is designed
      and constructed. This system is also called Remote Control of Microcontroller
      Based Infant Stimulation System or the RECOMBIS System. Cradle is an infant
      stimulating system that provides relaxation and sleeping for the baby. RECOMBIS
      system is designed for healthy full-term newborns to provide safe infant care and
      provide relaxation and sleeping for the baby. A microcontroller-based electronic
      circuit was designed and implemented for RECOMBIS system. Electromagnets were
      controlled by 8-bit PIC16F84 microcontroller, which is programmed using MPASM
      package. The system works by entering preset values from the keyboard, or pulse
      code modulated radio frequency remote control system. The control of the system
      and the motion range were tested. The test results showed that the system
      provided a good performance.

PMID- 10895427
TI  - Hepatitis C virus (HCV)

PMID- 10895428
TI  - Epidemiology of hepatitis C: geographic differences and temporal trends.
AB  - Hepatitis C Virus (HCV) infection appears to be endemic in most parts of the
      world, with an estimated overall prevalence of 3%. However, there is considerable
      geographic and temporal variation in the incidence and prevalence of HCV
      infection. Using age-specific prevalence data, at least three distinct
      transmission patterns can be identified. In countries with the first pattern
      (e.g., United States, Australia), most infections are found among persons 30-49
      years old, indicating that the risk for HCV infection was greatest in the
      relatively recent past (10-30 years ago) and primarily affected young adults. In
      countries with the second pattern (e.g., Japan, Italy), most infections are found
      among older persons, consistent with the risk for HCV infection having been
      greatest in the distant past. In countries with the third pattern (e.g., Egypt),
      high rates of infection are observed in all age groups, indicating an ongoing
      high risk for acquiring HCV infection. In countries with the first pattern,
      injection drug use has been the predominant risk factor for HCV infection,
      whereas in those with the second or third patterns, unsafe injections and
      contaminated equipment used in healthcare-related procedures appear to have
      played a predominant role in transmission. Much of the variability between
      regions can be explained by the frequency and extent to which different risk
      factors have contributed to the transmission of HCV. Because different strategies
      are required to interrupt different patterns of HCV transmission, determining the
      epidemiology of HCV infection in areas where that information has not yet been
      assessed is critical for developing appropriate prevention programs.

PMID- 10895429
TI  - Recovery, persistence, and sequelae in hepatitis C virus infection: a perspective
      on long-term outcome.
AB  - Hepatitis C has emerged in recent years as the most common basis for liver
      disease in the United States, having infected an estimated 3.9 million people in
      this country and an estimated 170 million worldwide. Currently, it is the
      predominant reason for undergoing liver transplantation. The disease it causes is
      characterized by silent onset in most infected individuals, a high rate of viral
      persistence, and the potential for development of ever-worsening chronic liver
      disease, ranging from chronic hepatitis to cirrhosis and occasionally to
      hepatocellular carcinoma. Such progression, when it occurs, is also most commonly
      a silent process that may take 20-40, and occasionally even more, years to reach
      its end point. Because of these characteristics, it has been exceedingly
      difficult to accurately assess the natural history. Efforts to accomplish this
      have consisted of retrospective, prospective, and cohort studies. The most
      concerning data have derived from the retrospective study approach, generally
      performed at tertiary referral centers. Because these centers commonly attract
      persons with existing chronic liver disease, they have tended to describe a high
      rate of progression to cirrhosis and cancer. This "referral bias" is avoided in
      the prospective and cohort study approach, and data derived from these studies
      indicate a lower rate of progression and a correspondingly higher rate of either
      recovery or minimal liver disease. In this review, we briefly describe potential
      mechanisms of viral persistence; present detailed information on outcomes that
      have derived from retrospective, prospective, and cohort studies, involving both
      adults and children; examine the data regarding progression of fibrosis and of
      progression to hepatocellular carcinoma; consider cofactors that might enhance
      liver disease progression; and report the emerging data that suggest that
      spontaneous viral clearance may be higher than is currently believed. We conclude
      with the view that severe, life-threatening, progressive liver disease clearly
      occurs in a sizable minority (perhaps 30%) of chronically infected persons but
      speculate that fibrosis progression is neither linear or inevitable and hence
      that most hepatitis C virus carriers will have either a stable nonprogressive
      course or such indolent progression that they will die from an unrelated disease
      before the severe sequelae of hepatitis C become manifest or will have a
      sustained "curative" response to therapy. Although this view provides reasonable
      hope to the hepatitis C virus-infected individual, it does not deny the enormous
      burden this infection presents as the result of its high prevalence and global
      distribution. The sheer magnitude of the infected population will result in a
      large number with severe life-threatening liver disease even if the proportion of
      infected individuals that develop progressive disease is relatively small.

PMID- 10895430
TI  - Transmission, natural history, and treatment of hepatitis C virus infection in
      the pediatric population.
AB  - Compared with the adult population, hepatitis C virus infection may differ in the
      pediatric age group with respect to transmission, course, and response to
      treatment. The prevalence of hepatitis C in children is between 0.05% and 0.4%.
      The major mode of acquisition has shifted from parenteral transmission to
      maternal-infant transmission. However, the actual rate of maternal-infant
      transmission is low. The natural history of hepatitis C in children is not well
      characterized, although the available information suggests a milder disease than
      in adults. In the eight studies of treatment with interferon for hepatitis C in
      children, the incidence of a complete sustained response varied from 0 to 45%. No
      pediatric studies have evaluated quality of life or the effect of treatment on
      the development of cirrhosis and hepatocellular carcinoma. Children may respond
      better to treatment than adults. We recommend that children with hepatitis C are
      considered for treatment only as part of a controlled clinical trial.

PMID- 10895431
TI  - Fibrosis in patients with chronic hepatitis C: detection and significance.
AB  - Estimates of the extent of hepatic fibrosis and the rate of fibrosis progression
      represent important surrogate end points for evaluation of the vulnerability of
      an individual patient and for assessment of the impact of treatment on natural
      history in chronic hepatitis C. Using the median fibrosis progression rate, the
      median expected time to cirrhosis in untreated patients is around 30 years.
      However, one third of patients have an expected median time to cirrhosis of less
      than 20 years and one third will only progress to cirrhosis in more than 50
      years, if ever. Factors independently associated with fibrosis progression are
      duration of infection, age, male gender, consumption of alcohol, human
      immunodeficiency virus co-infection, and low CD4 count. Evaluation of fibrosis
      progression is useful to decide treatment. Among patients with sustained viral
      response, fibrosis regresses. Evaluation of fibrosis progression has permitted
      validation of the concept of suppressive therapy. Among patients without viral
      clearance, interferon alone or in combination with ribavirin significantly
      reduces fibrosis progression rate in comparison with progression before treatment
      and to control groups. There is a major need for noninvasive markers of liver
      fibrosis. None are clearly useful today for the diagnosis of early stages of
      fibrosis.

PMID- 10895432
TI  - Hepatitis C virus RNA codes for proteins and replicates: does it also trigger the
      interferon response?
AB  - Hepatitis C virus (HCV) is a positive sense virus with a genomic RNA molecule
      roughly 9,600 nucleotides in length. The single-stranded genomic RNA has a
      nontranslated region (NTR) at each end and a long open reading frame (coding
      region) in between. The 5'NTR and portions of the 3'NTR are the most conserved
      parts of HCV RNA. These conserved regions contain signals for replication and
      translation. Much of the 5'NTR is folded into a structure that binds ribosomes.
      This structure, an internal ribosome entry site, promotes the initiation of
      protein synthesis and is critical for HCV gene expression. The ribosome binding
      site may extend into the coding region; its exact boundaries are not known. The
      open reading frame encodes the HCV polyprotein, which is slightly more than 3,000
      amino acids in length. The 3'NTR plays a key role in HCV replication and may also
      influence the rate of HCV protein synthesis. During replication, the genomic RNA
      is copied by virally encoded enzymes into a complementary antigenomic RNA, which
      itself is a template for the synthesis of progeny RNAs. At steady state, genomic
      strands outnumber antigenomic strands about 10 to 1. HCV RNA replication is
      thought to take place in the cytoplasm and is an error-prone process. It
      generates a mixed population of RNA sequences (quasispecies), including mutants
      that may be more fit than the parental type, less fit, or equally fit (but
      distinct). Natural selection acts upon the progeny RNAs, causing the population
      to change and drift. Over time, mutation, selection, and population bottlenecks
      led to the evolution of varied genotypes. The HCV replication complex is a
      potential source of double-stranded RNA, a powerful inducer of interferon. Thus,
      HCV-specific double-stranded RNA may trigger the first steps of innate immunity;
      however, for unknown reasons, the immune system often fails to clear the
      infection. The plasticity of the HCV genome and the low level of HCV gene
      expression may counterbalance any immunostimulatory effects of HCV RNA and allow
      the virus to escape specific immune responses. Antisense drugs and ribozymes
      directed against HCV RNA are under investigation. Future interventions may
      include nucleic acid drugs (antisense and ribozymes) and smaller pharmaceuticals
      that bind to intricate structures in HCV RNA and HCV-specific double-stranded
      RNA. Infectious clones of HCV RNA are available. These clones and other systems
      for expressing HCV proteins pave the way for vaccine development.

PMID- 10895433
TI  - Biochemical and immunologic properties of the nonstructural proteins of the
      hepatitis C virus: implications for development of antiviral agents and vaccines.
AB  - Infection with the hepatitis C virus (HCV) is the major cause of non-A, non-B
      hepatitis worldwide. The viral genome, a positive-sense, single-stranded, 9.6-kb
      long RNA molecule, is translated into a single polyprotein of about 3,000 amino
      acids. The viral polyprotein is proteoytically processed to yield all the mature
      viral gene products. The genomic order of HCV has been determined to be C-->E1-
      >E2-->p7-->NS2-->NS3-->NS4A-->NS4B-->NS5A++ +-->NS5B. C, E1, and E2 are the
      virion structural proteins. Whereas the function of p7 is currently unknown, NS2
      to NS5B are thought to be the nonstructural proteins. Generation of the mature
      nonstructural proteins relies on the activity of viral proteinases. Cleavage at
      the NS2-NS3 junction is accomplished by a metal-dependent autocatalytic
      proteinase encoded within NS2 and the N-terminus of NS3. The remaining downstream
      cleavages are effected by a serine proteinase contained also within the N
      terminal region of NS3. NS3, in addition, contains an RNA helicase domain at its
      C-terminus. NS3 forms a heterodimeric complex with NS4A. The latter is a membrane
      protein that acts as a cofactor of the proteinase. Although no function has yet
      been attributed to NS4B, NS5A has been recently suggested to be involved in
      mediating the resistance of the HCV to the action of interferon. Finally, the
      NS5B protein has been shown to be the viral RNA-dependent RNA polymerase. This
      article reviews the current understanding of the structure and the function of
      the various HCV nonstructural proteins with particular emphasis on their
      potential as targets for the development of novel antiviral agents and vaccines.

PMID- 10895434
TI  - Distribution of markers of hepatitis C virus infection throughout the body.
AB  - The detection of markers of hepatitis C virus (HCV) infection is complicated by
      the presence of virus in circulating blood. Consequently, it is necessary to
      target the negative-strand virus RNA or the nonstructural proteins. This has
      proved challenging, due to unforeseen difficulties in the specific detection of
      negative-strand viral RNA. However, recent data suggest that although the liver
      is the major target organ, the virus may be able to replicate in peripheral blood
      mononuclear cells, lymph nodes, and pancreas and to a more limited degree in bone
      marrow cells, thyroid, adrenal glands, and spleen. An analysis of the
      distribution of virus-infected cells in the liver has proved equally challenging.
      It is clear from the paucity of data generated by immunoblot and Northern blot
      hybridization that the level of HCV replication in the liver is very low, and
      this has necessitated studies to detect the viral RNA and antigens by in situ
      hybridization and immunohistochemistry, respectively. The results of these
      studies are quite disparate. Those related to in situ hybridization are
      nonreproducible and reflect wide disparities in the methodology used by different
      research workers. The data are often internally inconsistent or are inconsistent
      with data generated by nucleic acid amplification methods to detect the viral RNA
      in purified RNA extracts or inconsistent with our current understanding of the
      virus replication cycle. In contrast, the detection of the viral proteins is more
      reproducible, and some consensus can be reached. It is clear that frozen sections
      rather than formalin-fixed paraffin-embedded tissue are preferable. Indeed, it is
      likely that the use of the latter samples can generate nonspecific positive
      reactions. Surprisingly, many of the most useful data were derived by the use of
      polyclonal human antibodies from chronic carriers. HCV proteins were detected in
      the cytoplasm of infected hepatocytes, often in a punctate granular pattern in
      some hepatocytes and occasionally in monocytes and other cell types. There is
      often no correlation between HCV antigen expression and the degree of liver cell
      injury, although patients with lower levels of antigen expression are more likely
      to respond to interferon therapy.

PMID- 10895435
TI  - Clinical significance of hepatitis C virus genotypes and quasispecies.
AB  - Hepatitis C virus (HCV) is a major cause of morbidity and mortality worldwide.
      The infection becomes chronic in about 85% of infected individuals, in the face
      of a strong humoral and cellular immune response. One of the most important
      features of HCV is its high degree of genetic variability, which is due to the
      inherent low fidelity of the viral replication machinery. As a consequence, HCV
      circulates in vivo as a population of divergent, albeit closely related, genomes
      exhibiting a distribution that follows the model referred to as a quasispecies.
      The genetic variability of HCV is complex and has been classified into four
      hierarchical strata: genotypes, subgenotypes, isolates, and quasispecies. Over
      the past few years, an extraordinary interest has been focused on the biologic
      and clinical implications of the genetic variability of HCV. Although there is
      consensus that the genotypes may influence the out come of antiviral therapy,
      their clinical significance in the natural history of the disease, as well as in
      transmission, infectivity, and pathogenesis of HCV infection, remains elusive.
      Conversely, evidence has accumulated that the quasispecies nature of HCV provides
      a large reservoir of biologically different viral variants that may have
      important clinical implications for viral persistence by immune escape
      mechanisms, for the generation of antiviral drug resistance, and for the
      development of an effective vaccine. This article reviews the state of the art on
      the biologic and clinical implications of the genetic variability of HCV.

PMID- 10895436
TI  - Introduction to hepatitis B transplantation.

PMID- 10895437
TI  - Overview of hepatitis B and transplantation in the hepatitis B patient.
AB  - Hepatitis B is a disease that infects 300,000 people in the United States each
      year, resulting in 15,000-30,000 cases of chronic hepatitis. Outcomes include
      death; development of chronic carrier state, chronic hepatitis, fibrosis,
      cirrhosis, and hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg)
      carriers, especially those with cirrhosis, are at high risk for development of
      hepatocellular carcinoma. Histologically, chronic carriers of HBsAg may have a
      range of degree of tissue changes, ranging from normal, to varying degrees of
      portal or lobular inflammation, to significant cell injury with widespread
      necrosis, fibrosis and cirrhosis. Current histological grading systems reflect
      both graded inflammation and stage of fibrosis.

PMID- 10895438
TI  - Transplantation in the hepatitis B patient and current therapies to prevent
      recurrence.
AB  - Hepatitis B is the sixth most common indication for liver transplantation in the
      United States, accounting for about 7% of all transplants among adults.
      Transplantation for hepatitis B is especially problematic because the virus is
      not eradicated and there is great potential for reinfection that can lead to
      graft failure or death. This risk is higher still in patients with active viral
      replication and chronic liver disease. Treatment with short-term hepatitis B
      immune globulin (HBIG) delays reinfection of the allograft, but only long-term
      treatment with HBIG has led to a decline in the reinfection rate. Combination
      therapy using HBIG with nucleoside analogues will likely become the standard of
      care to maintain stable serum titers of protective anti-HBs antibody and to
      prevent posttransplantation reinfection.

PMID- 10895440
TI  - Posttransplantation: future therapies.
AB  - Recent advances in prophylaxis and treatment of hepatitis B virus (HBV) infection
      after liver transplantation have improved the outcome of liver transplantation
      for hepatitis B. Currently, the long-term use of hepatitis B immune globulin
      (HBIG) and/or nucleoside analogues are the only effective therapies to prevent or
      ameliorate HBV recurrence in liver transplant patients. However, they are very
      expensive, and breakthrough infections due to resistant HBV mutants are not
      infrequent. New strategies are being sought to decrease the risks of breakthrough
      infection and to increase the cost-effectiveness of liver transplantation for
      hepatitis B. Vaccination to prevent de novo infection is strongly recommended
      before transplantation, despite a decreased response in this immunosuppressed
      population. Adoptive transfer of immunity with such therapies as bone marrow or
      cytotoxic T lymphocyte transplants or xenotransplantation of an organ from a
      donor, which is not susceptible to infection by HBV may be effective in
      preventing or treating recurrent HBV posttransplantation. In addition, gene
      therapies and use of nucleoside and nucleotide analogues to disrupt various
      stages of the HBV life cycle may prevent or slow viral replication or assembly of
      the virus. Ultimately, the most effective therapy for the prevention of recurrent
      hepatitis B after liver transplantation will involve a combination of HBIG with
      one or more of the new antiviral agents.

PMID- 10895439
TI  - Posttransplantation: emerging and future therapies.
AB  - Liver transplantation in patients infected with hepatitis B virus (HBV) commonly
      results in reinfection that, if untreated, often compromises the viability of the
      allograft and negatively influences survival. Posttransplant treatment with
      hepatitis B immune globulin (HBIG) is now the standard of care, but patients
      appear to require lifelong treatment to prevent reinfection. In the past several
      years, new management strategies in patients with HBV have been developed, with
      an aim to decrease HBV-DNA replication before transplantation. Such an approach
      should increase the success of transplantation by decreasing the risk of
      reinfection and thus preventing recurrent disease posttransplantation. Nucleoside
      analogues, either alone or in conjunction with HBIG, are currently in use and are
      being studied in clinical trials as a means of preventing viral recurrence.
      Ganciclovir, famciclovir, and lamivudine all have demonstrated efficacy, although
      they vary in terms of effectiveness. Resistance may develop with the use of these
      agents and leads to reinfection by the mutant virus. Combination therapy may
      minimize the risk of viral mutation. Research continues to search for more
      effective ways to prevent and, if necessary, treat viral recurrence in patients
      undergoing liver transplantation for HBV.

PMID- 10895441
TI  - Hepatitis B transplantation: special conditions.
AB  - Patients with hepatitis B virus (HBV) infection may be coinfected with other
      viral diseases, such as hepatitis C virus (HCV) and/or D virus (HDV), or have
      serious diseases secondary to the hepatitis, such as hepatocellular carcinoma.
      These coexisting conditions have an impact on the success of treatment and of
      liver transplantation. Patients with HBV and HDV are at lower risk for HBV
      recurrence than are patients with HBV alone; likewise, patients with HBV/HCV
      coinfection appear to have a higher 5-year survival rate posttransplantation.
      Treatment of coinfection is similar to that used for HBV alone. Hepatitis B
      immune globulin and interferon have been found to be effective in varying
      degrees. Recurrence or reinfection of disease after liver transplantation
      presents many clinical problems that will require new therapeutic approaches.
      Future studies will help to begin solving these challenges.

PMID- 10895442
TI  - Case studies of the hepatitis B patient: a panel discussion.
AB  - In recent years, there have been significant advances in the treatment of
      patients with hepatitis B who are candidates for liver transplantation. This
      includes the prevention and management of hepatitis B posttransplantation.
      However, there is no established protocol for treating these patients.
      Ultimately, the goal would be to have patients HBV-DNA negative
      pretransplantation and then to prevent HBV recurrence posttransplantation to help
      ensure their quality of life. Several clinical case scenarios are presented and
      possible treatment solutions have been suggested. The timing of a transplant is
      critical due to the risk of viral mutation while the patient is on a nucleoside
      analogue antiviral agent and waiting for an organ. One successful option might be
      to start therapy pretransplant and continue it posttransplant. Combination
      therapy appears to provide the most effective course of treatment. This should
      include a nucleoside analogue and patients should be covered with hepatitis B
      immune globulin throughout the course of therapy. Several other variations of
      combination therapy are discussed, but many clinical issues remain to be
      resolved. Guidelines for future studies designed to answer these questions are
      proposed.

PMID- 10895443
TI  - Hypoplastic left heart syndrome.
AB  - Hypoplastic left heart syndrome may be accurately diagnosed during fetal life.
      Prenatal diagnosis provides the opportunity for parents to make an informed
      choice about their options, including surgery, nonintervention postnatally or
      termination of pregnancy. Short to medium term survival continues to improve for
      a condition that was previously invariably lethal. There continues to be a
      significant mortality and morbidity associated with hypoplastic left heart
      syndrome, and the long-term prognosis is unknown. Knowledge of the condition
      prior to birth means that babies who are to undergo surgery present in optimal
      condition for such interventions. Parents who have had an affected fetus or child
      should be offered detailed fetal echocardiography to exclude a recurrence in
      subsequent pregnancies.

PMID- 10895444
TI  - Breast ultrasound: new frontiers in imaging?

PMID- 10895445
TI  - Congenital microcephaly detected by prenatal ultrasound: genetic aspects and
      clinical significance.
AB  - OBJECTIVE: The aim of this study was to analyze fetuses with prenatally diagnosed
      microcephaly including the nature of associated anomalies and the genetic
      diagnostic implications. DESIGN: Retrospective study design. METHODS: A total of
      30 fetuses with reliable dates and with prenatally diagnosed microcephaly as a
      common feature were analyzed. RESULTS: Microcephaly was diagnosed at a mean
      gestational age of 28 weeks. More than half of the fetuses were also small for
      gestational age. Five subsets of microcephaly emerged from this study: (1)
      isolated microcephaly (16.7%); (2) microcephaly due to holoprosencephaly (16.7%);
      (3) microcephaly associated with chromosomal disorders (23.3%); (4) microcephaly
      as part of a genetic syndrome (20.0%); and (5) microcephaly as part of multiple
      anomalies (23.3%). CONCLUSIONS: In 25 out of 30 infants microcephaly proved to be
      part of a complex problem, emphasizing the need of a meticulous search for
      structural anomalies and fetal karyotyping when biometric data are not according
      to gestational age. The etiologic heterogeneity and variability of microcephaly
      in genetic syndromes are among the more difficult issues in prenatal ultrasound
      in pregnancies either with an incidental finding of this anomaly, or in cases
      with a recurrence risk. The complex situations described in this study
      demonstrate the importance of follow up, post-mortem investigation and careful
      genetic counseling.

PMID- 10895446
TI  - Prediction of preterm birth by second trimester cervical sonography in twin
      pregnancies.
AB  - OBJECTIVES: To determine the predictive value of sonographic cervical length and
      of funneling for spontaneous preterm delivery (PTD) in twin pregnancies under 26
      weeks' gestation. METHODS: Women with twin pregnancies were studied prospectively
      with transvaginal or translabial ultrasound of the cervix from 18 to 26 weeks'
      gestation. Exclusion criteria were: signs of preterm labor, prophylactic cervical
      cerclage, placenta previa, or severe congenital fetal anomaly. The primary
      outcome was spontaneous preterm birth at < 35 weeks' gestation. RESULTS: Sixty
      five twin pregnancies were analyzed, of which 23% (15/65) delivered preterm.
      Cervical ultrasound examination was performed by 22 weeks' gestation in 75% and
      by 24 weeks' gestation in 91% of women. Cervical length < or = 25 mm and < or =
      30 mm was associated with sensitivities of 27% and 53%, respectively, and with
      67% and 62% rates of PTD, respectively (R.R. 4.6, C.I. 2.0-10.3 and R.R. 3.6,
      C.I. 1.6-7.8, respectively). A cervical length > 35 mm was associated with only a
      4% rate of PTD (R.R 0.13; C.I. 0.02-0.93). Of 10 women (15%) with any cervical
      funneling, 70% delivered preterm, all under 32 weeks' gestation. By logistic
      regression analysis, both short cervix < or = 30 mm and any funneling were
      strongly predictive of PTD. CONCLUSIONS: Both cervical length < or = 30 mm and
      cervical funneling in twin pregnancies under 26 weeks' gestation are
      independently and strongly associated with high risk for preterm birth. A long
      cervix, of length > 35 mm, is associated with very low risk (4%) for preterm
      birth.

PMID- 10895447
TI  - Cervical assessment at the routine 23-weeks' scan: problems with transabdominal
      sonography.
AB  - OBJECTIVES: To compare transabdominal and transvaginal sonographic measurements
      of cervical length in pregnancy and examine the factors that may influence these
      measurements. METHODS: The study population consisted of 149 women with singleton
      pregnancies attending for routine ultrasound examination at 23 weeks of
      gestation. In all women the cervix was successfully visualized by transvaginal
      sonography and cervical length was measured after emptying of the bladder. This
      measurement was compared to that obtained by transabdominal sonography. In
      addition the ability to visualize the cervix transabdominally was examined in
      relation to body mass index (BMI), bladder volume and cervical length. RESULTS:
      The percentage of cases in which the cervix could be seen transabdominally
      increased from 42% for bladder volume of < 50 ml to 73% for volumes > 150 ml, and
      13% for cervical length < 20 mm to 51% for lengths > 40 mm. The ability to
      visualize the cervix was unrelated to BMI. Although there was a significant
      association between measurements taken transabdominally with those made
      transvaginally, measurements taken with a full bladder were significantly longer
      than those with an empty bladder. CONCLUSION: The aim of cervical assessment in
      pregnancy is to identify women with a short cervix because they are at high risk
      of preterm delivery. This aim can not be fulfilled by transabdominal sonography.
      Such a scan fails to visualize the cervix in a high proportion of cases and in
      particular those with a short cervix. Furthermore, successful visualization
      requires a full bladder which falsely increases cervical length.

PMID- 10895448
TI  - Intra- and interoperator repeatability of the nuchal translucency measurement.
AB  - OBJECTIVE: The aim of this study was to assess the repeatability of nuchal
      translucency measurement by well-trained sonographers either experienced or
      inexperienced with the measurement. METHODS: The nuchal translucency was measured
      three times by two out of nine operators in 161 pregnant women attending two
      teaching hospitals. Intra-operator and inter-operator variation was assessed by
      calculating the standard deviation (SD). Intraclass Correlation Coefficients
      (ICC) with a 95% lower confidence limit (95% CL) were calculated for each
      operator and for pairs of operators. Intra- and inter-operator kappa statistics
      were calculated, after dichotomising the results into a nuchal translucency
      smaller or larger than 3 mm. RESULTS: The SD of intra-operator difference was
      0.35 mm. The intra-operator repeatability showed ICCs varying from 0.83 to 0.95
      for the experienced operators and from 0.47 to 0.83 for the inexperienced. The SD
      of inter-operator differences was 0.56 mm, 0.46 mm and 0.44 mm, based on one, two
      and three measurements, respectively. The inter-operator repeatability showed a
      variation in ICC from 0.74 to 0.95 in pairs of experienced sonographers to 0.51
      in one pair inexperienced with the measurement. The kappa value expressing the
      intra and inter-operator repeatability as being > 3 mm or < 3 mm was 0.88 and
      0.85, respectively. CONCLUSION: This study supports the finding that the nuchal
      translucency measurement is reproducible, as long as it is performed by
      sonographers well trained in the technique of this measurement.

PMID- 10895449
TI  - Transabdominal first trimester embryofetoscopy as a potential approach to early
      in utero stem cell transplantation and gene therapy.
AB  - OBJECTIVE: To explore the potential of embryofetoscopy for early diagnosis and
      for access to the fetal circulation in the first trimester of gestation. DESIGN:
      Transabdominal embryofetoscopy was performed in 14 patients scheduled for
      termination of pregnancy using a 1-mm semirigid fibreoptic telescope with a 18
      gauge examination sheath and a single-chip digital camera. A 25 gauge needle was
      inserted through an additional 21 gauge side port to access the fetal
      circulation. RESULTS: Fetal head, face, abdomen, complete upper and lower limbs
      could be visualized in over 80% of cases. On the contrary, the fetal back and
      external genitalia could be examined in detail only in some cases (35.7% and
      64.3%, respectively). Injection of 10-20 ml saline improved visibility in 43% of
      cases. Funipuncture was successful in two of three attempts. CONCLUSIONS: Our
      experience suggests that embryofetoscopy is a useful tool for early diagnosis in
      the first trimester of pregnancy. Funipuncture is possible thus providing the
      means for an early intravascular stem cell application.

PMID- 10895450
TI  - Fetal penile length.
AB  - OBJECTIVE: To construct a reference range for fetal penile length. METHODS: The
      length of the penis was measured during ultrasound assessment of 95 structurally
      normal male fetuses of gestational ages 16-38 weeks. Two fetuses with bladder
      outflow obstruction were also examined. RESULTS: Fetal penile length increases
      significantly with gestational age, from a mean value of 6.0 mm at 16 weeks to
      26.4 mm at 38 weeks. One fetus with urethral agenesis had a penile length on the
      0.3rd centile. CONCLUSIONS: Measurement of the fetal penis is easy and not time
      consuming. In cases of bladder outflow obstruction, assessment of penile length
      assists in the differentiation between urethral agenesis and posterior urethral
      valves.

PMID- 10895451
TI  - Does texture analysis improve breast ultrasound precision?
AB  - OBJECTIVE: To evaluate the possibility of distinguishing between benign and
      malignant breast tumors using a computer-aided evaluation of echogenicity and
      echostructure of ultrasound findings at certain focal points. STUDY DESIGN: The
      ultrasound images from 89 cases of breast tumor were documented under
      standardized conditions using a linear array machine and 7.5 MHz transducer. In
      each sonographic image, the maximum area of the 'region of interest' of the tumor
      was marked and then subjected to consecutive statistical analysis and correlation
      with the histological findings. For evaluation of tumor status eight parameters
      of first and second order texture statistics (gray level histogram, Fourier
      analysis, co-occurrence matrix) were applied. RESULTS: Benign tumors were clearly
      distinguished from carcinomas in the evaluation of the co-occurrence matrix and
      the Fourier analysis on the basis of Wilcoxon and Student t-test (P < 0.05) but
      not in the gray level histogram. Using logistic regression a sensitivity of 73.8%
      and a specificity of 54.2% were obtained. A statistically significant difference
      between benign tumors and moderately differentiated together with poorly
      differentiated carcinomas could be demonstrated. CONCLUSION: This study concludes
      that texture analysis appears to distinguish between benign and most malignant
      tumors. A computer texture analyzing system is able to improve the subjective
      assessment of ultrasound images of the breast but can not replace it. Where the
      limits of subjective assessment of a given tumor are reached, computerized
      texture analysis will provide additional information in the differentiation of
      benign from malignant findings.

PMID- 10895452
TI  - Endometrial thickness and histological abnormalities in women on hormonal
      replacement therapy: a transvaginal ultrasound/hysteroscopic study.
AB  - OBJECTIVES: The aim of this study was to assess if endometrial thickness could be
      used to select postmenopausal women on hormonal replacement therapy (HRT) at
      increased risk for endometrial abnormalities. The secondary aim was to assess if
      endometrial abnormalities were more likely to occur in patients with increased
      endometrial thickness or in patients with unexpected bleeding. METHODS: Bi
      endometrial thickness was measured by transvaginal ultrasound (TVS) in
      postmenopausal patients on sequential or combined HRT regimens. Women following a
      sequential regimen underwent TVS examination immediately after their withdrawal
      bleed, always between 5 and 10 days after the last progesterone tablet. A
      hysteroscopy with endometrial biopsy was performed within 5 days after the TVS
      examination, when endometrial thickness was > or = 4 mm, or when unscheduled
      bleeding was observed. RESULTS: A total of 190 women were recruited. In 138 women
      on sequential regimens, the mean value of endometrial thickness was 3.6 mm +/-
      1.5, and in 52 women on combined regimens it was 3.2 mm +/- 1.8 (P = n.s.) Twenty
      eight patients (15%) had an endometrial thickness > 4 mm, 35 patients (18.4%)
      reported unexpected bleeding. The percentage of abnormal endometrial findings
      (9%; three of 35) in patients selected for unscheduled bleeding was significantly
      lower than the percentage of abnormal findings in patients selected for
      hysteroscopy for endometrial thickness > 4 mm (36%; 10 of 28) (P < 0.01). All
      patients with unexpected bleeding and endometrial thickness < or = 4 mm (24
      cases) were found to have an atrophic endometrium. CONCLUSIONS: Endometrial
      thickness in patients on sequential HRT, measured soon after withdrawal bleeding,
      is not significantly different from thickness measured in patients on combined
      HRT. Patients on HRT with an endometrial thickness of > 4 mm could be considered
      for histological sampling. The prevalence of abnormal endometrial findings in
      patients with a thick endometrium is significantly higher than the prevalence
      observed in patients with unexpected bleeding.

PMID- 10895453
TI  - Errors in the measurement of endometrial depth using transvaginal sonography in
      postmenopausal women on tamoxifen: random error is reduced using saline
      instillation sonography.
AB  - OBJECTIVE: The endometrium in women on tamoxifen is often made irregular by small
      cysts. The aim of this study was to assess the accuracy and precision of the
      measurement of endometrial depth by transvaginal sonography. METHODS: The
      endometrial depth from endometrial biopsies obtained with the resectoscope in 15
      women receiving tamoxifen was compared to the endometrial depth measured by TVS.
      The inter-observer variability was measured in 58 women. RESULTS: In those
      biopsies of sufficient quality to allow a measurement, the corresponding depth
      measurement obtained by ultrasound was up to 3 mm greater than the histological
      measurement. The interobserver variability for the measurement of endometrial
      depth using TVS was assessed in 58 postmenopausal women on tamoxifen. The
      interobserver variability deteriorated as the mean endometrial depth increased,
      probably because the increase in depth resulted from greater morphological
      changes within the endometrium such as cyst formation which resulted in an
      irregular endometrial/myometrial boundary. This may, however, be improved by
      performing saline instillation sonography. In a prospective study of 10
      postmenopausal women, the interobserver variability was significantly greater
      during tamoxifen treatment compared to pretreatment. CONCLUSIONS: On the basis of
      the above, if uterine surveillance using TVS were to be offered to postmenopausal
      women on tamoxifen, then the procedure should be augmented by saline instillation
      sonography if the endometrial depth is > 4 mm, as this will improve the
      measurement precision and also identify intrauterine pathology.

PMID- 10895454
TI  - The bright edge of the endometrial polyp.
AB  - OBJECTIVE: To evaluate the accuracy of sonographic detection of endometrial
      polyps using a new ultrasound marker denoted 'the bright edge of the polyp'.
      METHODS: The ultrasound scans of the uterus were examined for the presence of the
      bright edge in two groups of women. The first, a retrospective group, included 40
      women in whom both a histological diagnosis of endometrial polyps and sonographic
      scans were available for evaluation. The second, a prospective group, included 80
      women scheduled for operative hysteroscopy because of endometrial irregularities
      detected by sonography. In this group the hysteroscopical and histological
      results of the removed endometrial tissue were correlated with the sonographic
      diagnosis. RESULTS: In the retrospective group, the bright edge marker,
      indicative of the presence of a polyp, was detected in 30 out of 40 scans
      available for evaluation. In the prospective group this marker was detected in 60
      women out of 80. Endometrial polyps were confirmed in 56 of these 60 women. In
      three cases a submucosal myoma was found and in one case the histology showed
      simple cystic hyperplasia. Two polyps were found in 20 cases where the bright
      edge had not been detected. This marker has a sensitivity of 96%, specificity of
      82%, positive predictive value of 93%, and negative predictive value of 90% in
      this group at high risk for endometrial abnormalities. CONCLUSION: The bright
      edge of the polyp is an accurate sonographic marker for the detection of
      endometrial polyps in women with endometrial irregularities demonstrated on
      ultrasound.

PMID- 10895455
TI  - Prenatal diagnosis of fetal nephrolithiasis.

PMID- 10895456
TI  - Prenatal diagnosis of an aneurysm of the vein of Galen with three-dimensional
      color power angiography.
AB  - The prenatal diagnosis of an aneurysm of the vein of Galen has been reported on
      only a few occasions. This rare arterio-venous fistula is suspected when an
      intracerebral hypoechoic cyst is found in which blood flow can be demonstrated by
      Doppler ultrasound. This is one of the few conditions where Doppler ultrasound is
      critical for the diagnosis. Three-dimensional color power Doppler (3D-CPA) is a
      recent ultrasound modality which enables the three-dimensional visualization of
      vessels and which is more readily available than magnetic resonance imaging (MRI)
      We report a fetus in which an aneurysm of the vein of Galen was detected at 33
      weeks' gestation and where the application of 3D-CPA enabled a better
      understanding of the spatial orientation and course of the dilated vessels. The
      neonate was successfully treated with coil angiography but subsequently died at 5
      months of age from cardiac decompensation. Where fetal malformations involve the
      vascular system, 3D-CPA appears to be a promising technique.

PMID- 10895458
TI  - Three-dimensional color power angiography of an aneurysm of the vein of Galen.

PMID- 10895457
TI  - Prenatal depiction of angioarchitecture of an aneurysm of the vein of Galen with
      three-dimensional color power angiography.
AB  - A fetus with a large supratentorial cyst and cardiomegaly was encountered at 33
      weeks of gestation. The cyst appeared as an aneurysmal, fluid-filled structure
      extending posteriorly with a finger-like appendage. Using color flow mapping, we
      disclosed rapid in-and-out blood flow with marked turbulence within the cyst. For
      evaluation of its blood supply and venous drainage of the vascular malformation,
      a three-dimensional reconstruction of the power Doppler image was conducted. The
      results revealed that the vascular malformation was supplied by a small
      contralateral aneurysm from the branches of Willis' circle, draining posteriorly
      into an abnormal falcine sinus and then into the superior sagittal sinus. No
      other fetal abnormality such as hydrocephalus or hydrops was discovered. The
      prenatal diagnosis of an aneurysm of the vein of Galen was made on the basis of
      the gray-scale, color Doppler findings, and also the angioarchitecture obtained
      by three-dimensional power Doppler imaging. The woman was admitted at 37 weeks of
      gestation due to labor onset and delivered the baby via the vaginal route without
      complication. Postnatal angiography and magnetic resonance imaging confirmed the
      diagnosis of an aneurysm of the vein of Galen, and the angioarchitecture depicted
      it before birth. We suggest that three-dimensional power Doppler ultrasonography
      may assist in the diagnosis of an aneurysm of the vein of Galen, and precisely
      delineate the complicated corresponding vasculature. This may guide postnatal
      management and predict the prognosis more accurately.

PMID- 10895459
TI  - Diagnosis of Asherman's syndrome with three-dimensional ultrasound.

PMID- 10895460
TI  - Rapid diagnosis and treatment of post-cesarean parametrial abscess by
      transabdominal ultrasound-guided needle aspiration.

PMID- 10895461
TI  - Prenatal depiction of the angioarchitecture of an aneurysm of the vein of Galen
      with three-dimensional color power angiography.

PMID- 10895462
TI  - [Andrology in the next millenium].

PMID- 10895463
TI  - [Before dementia--early features in Alzheimer's disease].

PMID- 10895464
TI  - [Manipulation of the cervical area--a critical review of its effectiveness and
      complications].

PMID- 10895465
TI  - [Hereditary polycystic liver disease].

PMID- 10895466
TI  - [Corrosive injury of proximal esophagus caused by strong drain detergent].

PMID- 10895467
TI  - [Chronic pain and other symptoms following treatment of breast cancer].

PMID- 10895468
TI  - [Fever, polyarthritis and varicose ulcer as manifestations of the gout].

PMID- 10895469
TI  - [Unclear fever in a school child].

PMID- 10895470
TI  - [Function of the kidney 1: glomerulus].

PMID- 10895471
TI  - [Treatment of social phobia].

PMID- 10895472
TI  - [Red eyes].

PMID- 10895473
TI  - [Elevated blood pressure and headache in a student].

PMID- 10895474
TI  - [Congratulations to the editors and authors of Duodecim's Christmas number].

PMID- 10895475
TI  - [General practitioner's handbook and data base--in ten years to a concept].

PMID- 10895476
TI  - [Mother, child and coronary artery disease].

PMID- 10895477
TI  - [Conservative treatment of urinary stress incontinence in women].

PMID- 10895478
TI  - [Occupational causes of lung cancer].

PMID- 10895479
TI  - [Cerebral amyloid angiopathy--an underdiagnosed cause for cerebral hemorrhages].

PMID- 10895480
TI  - [From practice to theory--and back. Treatment recommendations as a part of the
      development strategy for quality in health care].

PMID- 10895481
TI  - [Carbamazepine medication paralyzed the elderly man].

PMID- 10895482
TI  - [Function of the kidney II: tubule and collecting tubule].

PMID- 10895483
TI  - [Achilles tendon ruptures are increasing--surgical or conservative treatment?].

PMID- 10895484
TI  - [The treatment of acne].

PMID- 10895485
TI  - [A child with chronic abdominal problems].

PMID- 10895486
TI  - [Prolonged fever].

PMID- 10895487
TI  - [Does evolution theory offer help to the problems of medicine?].

PMID- 10895488
TI  - [Location, profession and variation in sick days].

PMID- 10895489
TI  - [EHEC infections in Finland].

PMID- 10895490
TI  - [Does exercise cause eating disorders?].

PMID- 10895491
TI  - [Lung computer tomography guided fine-needle biopsies].

PMID- 10895492
TI  - [Enterohemorrhagic Escherichia coli--infection and a hemolytic uremic syndrome].

PMID- 10895493
TI  - [Treatment of pruritus].

PMID- 10895494
TI  - [Cytostatic drugs in the treatment of rheumatic and connective tissue diseases].

PMID- 10895495
TI  - [Fever and neck ache in a middle-aged man].

PMID- 10895496
TI  - [An asymmetric pupil].

PMID- 10895497
TI  - [Adverse effects on health from pesticide use in the tropics].

PMID- 10895499
TI  - [Treatment of claudication].

PMID- 10895498
TI  - [Alkaptonuria--one more case].

PMID- 10895500
TI  - [Eyes open].

PMID- 10895501
TI  - [Aging population and developing techniques: blessing and curse of cataract
      surgery].

PMID- 10895502
TI  - [Radiotherapy in age-related macular degeneration].

PMID- 10895503
TI  - [Sudden disturbances of vision, carotid artery stenosis and risk of death].

PMID- 10895504
TI  - [New aspects on systemic adverse effects of ocular drugs].

PMID- 10895505
TI  - [Some light on the early phases of diabetic retinopathy].

PMID- 10895506
TI  - [Leber's optic neuropathy: a mitochondrial disease revealing its secret].

PMID- 10895507
TI  - The science blues.

PMID- 10895508
TI  - Debate over the history of placebos in medicine.

PMID- 10895509
TI  - Testing the immortality hypothesis.

PMID- 10895510
TI  - Exploring the use of hypnosis in surgery.

PMID- 10895511
TI  - Growing the path to the patient: an editorial outlook for Alternative therapies.

PMID- 10895512
TI  - Trance surgery in Brazil.
AB  - This report presents the results of fieldwork in Brazil on healer-mediums who
      perform crude forms of surgery, often employing sharp instruments. We found that
      these healer-mediums were in a hyperaroused brain state while they were engaged
      in behaviors commonly described in the anthropology literature as "possession
      trance"; therefore, this practice is termed "trance surgery" in this report. The
      research was conducted at widely scattered sites throughout Brazil. We observed
      several thousand patients being treated by 9 trance surgeons and videotaped
      several hundred of these cases. In addition to background information and our own
      observational material, this paper includes 2 medical case reports, physiological
      data gathered from healers and patients, and results of a pathologist's
      examination of a surgically excised tumor. Topographic brain mapping revealed
      increased brain activity (36-44 Hz) when healer-mediums were engaged in trance
      behaviors, compared to resting baseline conditions at midline scalp locations
      (Cz, P < .009 and Pz, P < .004; both matched t tests). These results suggest the
      presence of a hyperaroused brain state associated with the trance behaviors of
      the healers. We believe that such a state is required for this unusual practice,
      but other factors may also be involved. In contrast, a small sample of patients
      monitored during possession trance surgical procedures revealed no high-frequency
      brain activity; instead, there were indications of cortical quieting, suggesting
      relaxation, despite the absence of anesthesia. Pathohistological examination of a
      tumor excised from a patient in our presence revealed a human fibroadenoma. We
      conclude that these practices are usually benign and that pain is often absent,
      despite the lack of sterile procedures and anesthesia. Although during the period
      of our investigation we were informed anecdotally of 3 cases involving serious
      complications or death, we personally observed no cases of shock, hemorrhage, or
      death. The cases presented in this paper, as well as others we have followed,
      suggest that serious illnesses, not likely to improve without treatment, may do
      so after trance surgery procedures are performed. If the major benefit of trance
      surgery is to initiate self-healing processes, it would have to do so in powerful
      ways, which possibly can be elucidated with positron emission tomography and
      functional magnetic resonance imaging scans. Positive findings would be helpful
      in understanding large-scale healing effects and may lead to new treatment
      protocols.

PMID- 10895513
TI  - Results of dental amalgam removal and mercury detoxification using DMPS and
      neural therapy.
AB  - Sixty consecutive patients who had undergone replacement of dental amalgam
      fillings and a protocol of nutritional support and heavy metal detoxification
      using dimercapto-propanyl-sulfate and neural therapy were surveyed. A
      questionnaire was mailed to the patients and 42 responded, resulting in a
      response rate of 70%. The reasons for undergoing treatment were many, ranging
      from a patient's desire to avoid potential health problems in the future to
      treatment of serious current disease. Although medical diagnoses were made when
      possible before treatment, this survey studied only the patients' estimations of
      their most distressing symptoms and their evaluations of response to treatment.
      The most common complaints were problems with memory and/or concentration; muscle
      and/or joint pain; anxiety and insomnia; stomach, bowel, and bladder complaints;
      depression; food or chemical sensitivities; numbness or tingling; and eye
      symptoms, in descending order of frequency. The most distressing symptoms were
      headache and backache, fatigue, and memory and concentration problems. Headache
      and backache responded best to treatment, but all symptoms showed considerable
      improvement on average. Of the respondents, 78% reported that they were either
      satisfied or very satisfied with the results of treatment, and 9.5% reported that
      they were disappointed.

PMID- 10895514
TI  - Prayer and health outcomes in church members.
AB  - CONTEXT: This study adds to the existing research on religion and health by
      focusing on the specific practice of prayer and its relationship to health
      outcomes. OBJECTIVES: The purpose of this survey is to examine the relationship
      of frequency of prayer to 8 categories of physical and mental health. DESIGN: The
      Presbyterian Church, USA, performed data collection as part of an ongoing
      research program. Members of the Presbyterian Church were randomly selected from
      the national population and surveyed by mail on their frequency of prayer and
      their health status, as measured by the Medical Outcomes Study Short-form 36
      Health Survey. RESULTS: Self-reports of health indicated a high level of
      functioning overall for all 8 categories of physical and mental health. People
      who prayed more often scored lower in their physical functioning and their
      ability to carry out role activities, and higher in their reports of physical
      pain. However, people who prayed more often also had significantly higher mental
      health scores than did those who prayed less frequently, despite their physical
      health problems. CONCLUSION: This study supports the relationship of a high
      frequency of prayer with a more positive mental health. Various explanations of
      the results are explored.

PMID- 10895515
TI  - Culture, ritual, and errors of repudiation: some implications for the assessment
      of alternative medical traditions.
AB  - In this article, sources of error that are likely involved when alternative
      medical traditions are assessed from the standpoint of orthodox biomedicine are
      discussed. These sources include (1) biomedicine's implicit reductive materialism
      (manifested in its negative orientation toward placebo effects), (2) a related
      bias against ritual, and (3) cultural barriers to the construction of externally
      valid protocols. To overcome these biases, investigators must attend to
      ritualistic elements in alternative treatments and should recruit patients from
      appropriate cultural groups. Collaborative research may be the key. Benefits of
      collaborative research include (1) increased mutual respect and integration
      between culturally distinct groups and practices, (2) increased understanding and
      use of sophisticated techniques of empirical analysis among practitioners from
      the alternative traditions, (3) increased appropriation of the therapeutic
      benefits of ritual, and (4) enhanced overall benefit for patients of all cultural
      backgrounds.

PMID- 10895516
TI  - The effects of a short program of detoxification in disease-free individuals.
AB  - CONTEXT: Removal of toxins from the body is an integral part of Ayurvedic, yogic,
      and naturopathic medicine. Symptoms of poor health in people free from diagnosed
      disease may be related to toxin buildup. OBJECTIVE: This study investigates
      whether a 7-day program of detoxification can improve well-being and enhance the
      activity of liver detoxification pathways. METHODS: In this pilot, patient
      outcome-focused, noncontrolled clinical intervention, 25 disease-free
      participants were recruited. Pre- and postmeasures were taken using the Metabolic
      Screening Questionnaire (as a subjective assessment of well-being) and drug
      challenge tests to assess hepatic detoxification capacity. RESULTS: A
      statistically significant (47%) reduction in the Metabolic Screening
      Questionnaire scores resulted. This improvement in patient-assessed health
      occurred concurrently with a 23% increase in liver detoxification capacity, as
      reflected by the caffeine clearance measure. There was an increase in the urinary
      sulfate-to-creatinine ratio after treatment, indicating a trend toward improved
      liver function. DISCUSSION: In disease-free adults, a 7-day course of
      detoxification may produce improvements in subjective health reports. This
      simple, short-term intervention may be appropriate for disease-free individuals
      without specific toxin exposure, for the purpose of enhancing health and
      preventing the development of disease. CONCLUSIONS: A simple 7-day detoxification
      program resulted in a significant reduction in participant symptomology. The
      tendency toward improvement in liver detoxification measures is consistent with
      the hypothesis that improved liver detoxification capacity may contribute to well
      being.

PMID- 10895517
TI  - Alan Abromovitz, MD. Integrated patient care: one physician's story. Interview by
      Bonnie Horrigan.

PMID- 10895518
TI  - Regions Hospital opens holistic nursing unit.

PMID- 10895519
TI  - Three-mode principal components analysis: choosing the numbers of components and
      sensitivity to local optima.
AB  - A method that indicates the numbers of components to use in fitting the three
      mode principal components analysis (3MPCA) model is proposed. This method, called
      DIFFIT, aims to find an optimal balance between the fit of solutions for the
      3MPCA model and the numbers of components. The achievement of DIFFIT is compared
      with that of two other methods, both based on two-way PCAs, by means of a
      simulation study. It was found that DIFFIT performed considerably better than the
      other methods in indicating the numbers of components. The 3MPCA model can be
      estimated by the TUCKALS3 algorithm, which is an alternating least squares
      algorithm. In a study of how sensitive TUCKALS3 is at hitting local optima, it
      was found that, if the numbers of components are specified correctly, TUCKALS3
      never hits a local optimum. The occurrence of local optima increased as the
      difference between the numbers of underlying components and the numbers of
      components as estimated by TUCKALS3 increased. Rationally initiated TUCKALS3 runs
      hit local optima less often than randomly initiated runs.

PMID- 10895520
TI  - Distribution of the standardized mean change effect size for meta-analysis on
      repeated measures.
AB  - When conducting a meta-analysis on studies with repeated measures, a useful
      measure of effect size is Becker's (1988) standardized mean change. This paper
      examines the distributional properties of the standardized mean change, and
      discusses potential problems with the variance formulae given in Becker (1988).
      First, an error in the exact variance formula can lead to severe underestimation
      of the actual sampling variance. Second, Becker (1988) recommended the use of an
      approximation which is shown to underestimate the sampling variance when sample
      size is small. Using the approximation can decrease the accuracy of meta-analysis
      results; however, the degree of error is generally small.

PMID- 10895521
TI  - Robust transformation with applications to structural equation modelling.
AB  - Data sets in social and behavioural sciences are seldom normal. Influential cases
      or outliers can lead to inappropriate solutions and problematic conclusions in
      structural equation modelling. By giving a proper weight to each case, the
      influence of outliers on a robust procedure can be minimized. We propose using a
      robust procedure as a transformation technique, generating a new data matrix that
      can be analysed by a variety of multivariate methods. Mardia's multivariate
      skewness and kurtosis statistics are used to measure the effect of the
      transformation in achieving approximate normality. Since the transformation makes
      the data approximately normal, applying a classical normal theory based procedure
      to the transformed data gives more efficient parameter estimates. Three
      procedures for parameter evaluation and model testing are discussed. Six examples
      illustrate the various aspects with the robust transformation.

PMID- 10895522
TI  - An examination of the robustness of the empirical Bayes and other approaches for
      testing main and interaction effects in repeated measures designs.
AB  - In a previous paper, Boik presented an empirical Bayes (EB) approach to the
      analysis of repeated measurements. The EB approach is a blend of the conventional
      univariate and multivariate approaches. Specifically, in the EB approach, the
      underlying covariance matrix is estimated by a weighted sum of the univariate and
      multivariate estimators. In addition to demonstrating that his approach controls
      test size and frequently is more powerful than either the epsilon-adjusted
      univariate or multivariate approaches, Boik showed how conventional multivariate
      software can be used to conduct EB analyses. Our investigation examined the Type
      I error properties of the EB approach when its derivational assumptions were not
      satisfied as well as when other factors known to affect the conventional tests of
      significance were varied. For comparative purposes we also investigated
      procedures presented by Huynh and by Keselman, Carriere, and Lix, procedures
      designed for non-spherical data and covariance heterogeneity, as well as an
      adjusted univariate and multivariate test statistic. Our results indicate that
      when the response variable is normally distributed and group sizes are equal, the
      EB approach was robust to violations of its derivational assumptions and
      therefore is recommended due to the power findings reported by Boik. However, we
      also found that both the EB approach and the adjusted univariate and multivariate
      procedures were prone to depressed or elevated rates of Type I error when data
      were non-normally distributed and covariance matrices and group sizes were either
      positively or negatively paired with one another. On the other hand, the Huynh
      and Keselman et al. procedures were generally robust to these same pairings of
      covariance matrices and group sizes.

PMID- 10895523
TI  - Repeated measures ANOVA: some new results on comparing trimmed means and means.
AB  - This paper considers the common problem of testing the equality of means in a
      repeated measures design. Recent results indicate that practical problems can
      arise when computing confidence intervals for all pairwise differences of the
      means in conjunction with the Bonferroni inequality. This suggests, and is
      confirmed here, that a problem might occur when performing an omnibus test of
      equal means. The problem is that the probability of rejecting is not minimized
      when the means are equal and the usual univariate F test is used with the Huynh
      Feldt correction (epsilon) for the degrees of freedom. That is, power can
      actually decrease as the mean of one group is lowered, although eventually it
      increases. A similar problem is found when using a multivariate method
      (Hotelling's T2). Moreover, the probability of a Type I error can exceed the
      nominal level by a large amount. The paper considers methods for correcting this
      problem, and new results on comparing trimmed means are reported as well. In
      terms of both Type I errors and power, simulations reported here suggest that a
      percentile t bootstrap used with 20% trimmed means and an analogue of the epsilon
      adjusted F gives the best results. This is consistent with extant theoretical
      results comparing methods based on means with trimmed means.

PMID- 10895524
TI  - Modelling sequentially scored item responses.
AB  - The sequential model can be used to describe the variable resulting from a
      sequential scoring process. In this paper two more item response models are
      investigated with respect to their suitability for sequential scoring: the
      partial credit model and the graded response model. The investigation is carried
      out by first deriving a property of sequential scoring, which will be called item
      characteristic curve invariance, and then demonstrating that the partial credit
      model and the logistic graded response model do not accommodate this property.
      Therefore, when either of these two models is applied to sequentially scored
      variables, a specification error is made.

PMID- 10895525
TI  - Triadic distance models for the analysis of asymmetric three-way proximity data.
AB  - Triadic distance models can be used to analyse proximity data defined on triples
      of objects. Three-way symmetry is a common assumption for triadic distance
      models. In the present study three-way symmetry is not assumed. Triadic distance
      models are presented for the analysis of asymmetric three-way proximity data that
      result in a simultaneous representation of symmetry and asymmetry in a low
      dimensional configuration. An iterative majorization algorithm is developed for
      obtaining the coordinates and the representation of the asymmetry. The models are
      illustrated by an example using longitudinal categorical data.

PMID- 10895526
TI  - Modelling asymmetric similarity with prominence.
AB  - This paper introduces and discusses a geometrically based model, the relative
      prominence model, which is inspired by Tversky's finding that a factor behind
      asymmetric similarity seems to be 'relative prominence'. The model proposes that
      the experienced directed similarity from I to J is proportional to some symmetric
      similarity measure between I and J, and the quotient between the 'prominences'
      for J and I. Analysis of several empirical data sets shows that it is possible
      for a procedure to estimate the parameters of the model quite well. The
      differences between the relative prominence model and related models that handle
      asymmetry in terms of 'stimulus bias' are discussed.

PMID- 10895527
TI  - Mirko Drazen Grmek: the genesis of scientific fact and archaeology of disease.
AB  - Professor Mirko Drazen Grmek (Krapina 1924--Paris 2000) was one of the most
      prominent Croatian scientists. Work in history of science directed him to the
      crossroads of various fields placing his approach in anthropological perspective.
      Two models will serve as illustrations of his main theories. The historical
      reconstruction of scientific discovery (mostly on examples of 17th century) will
      be presented as well as Grmek's ideas on a concept of disease. The introduction
      of the term "memoricide" within his activities during aggression on Croatia is
      mentioned.

PMID- 10895528
TI  - Epidemiology of violence and war.
AB  - The magnitude of the threat that violence and war pose to the health, the quality
      of life, and the very survival of humanity is obvious. A number of scientific
      disciplines have provided, each through its own methodology, insights into the
      causation, genesis, and dynamics of violence and war. Although epidemiological
      and psychological methodologies received priority, the multidisciplinary approach
      to this problem seems to be the most appropriate. This essay attempts to approach
      holistically the study of epidemiology of violence and war and the ways of
      preventing these severe problems of the contemporary society. Conceptual models
      of the causative mechanisms and dynamics of violence and war, mapping the various
      psychic, social, and environmental factors, are presented. These models, besides
      advancing abstract ideas, also provide a concrete framework for determining and
      exploring the interactions and dynamics of the factors and processes which lead
      to violence and war. The types of interventions outlined for control and
      prevention are intended to make an impact upon "critical points" within the
      dynamics of the process which produces violence and war, and are conceived to be
      implemented on both the national and international level. The importance of
      family, community, and school influences is considered, but the role of
      international organizations, including the United Nations, and other governmental
      and non-governmental organizations is also stressed. Discussion is focused on the
      factors which favour peace and hamper aggression, on "internationalization" and
      global society versus xenophobia and nationalism. The conclusions state that
      there is sufficient knowhow to devise and implement a reasonable and effective
      international programme for the control and prevention of violence and war,
      provided there is adequate public and political willingness and support.

PMID- 10895529
TI  - Hope, Arkansas to Hope, Albania: naivete and idealism to reality and tragedy.
AB  - The wars in Croatia, Bosnia and Kosovo were perpretrated by a radical nationalist
      Serbian cultural political consciousness that the American cultural political
      consciousness and leadership had difficulty responding to and understanding.
      There is a great cultural divide between a 'pathology' in Serbian culture,
      Milosevic's radical nationalism, and a humane 'naivete' in American cultural
      consciousness. I discuss why, finally, American political leadership, Bill
      Clinton from Hope, Arkansas, responded to the tragedy of these wars. However, we
      are still left with the question of good vs evil: What is the course of human
      history; psychotic political leadership causing repetitive human tragedy or can
      there be a higher humane and moral order to human cultural events?

PMID- 10895530
TI  - Exile and the undestroyable perpetuity of stigmatizations--some critical
      (medical) anthropological reflections.
AB  - The writing of this paper has been stimulated by the observable widening
      dichotomy between present pluralist discourses of multiculturalism, which claim
      the future of mutual understanding and harmony vs. the true prevalence of a
      dramatically growing discordance in human relations world-wide. Given the
      experience of working in the long-term exile fieldwork, as well as coming from a
      geographically interesting and highly media-presented country, ones capacity to
      rethink and self-detect the modes of treating alterity seems to grow together
      with the imposed self-reflexivity. It remains to be seen whether the decades in
      which many have been on the receiving end of approaches that address the Other-
      the perceptual fields of "race" vs. race and visible vs. non-visible ethnicity's,
      etc.--will yield an output of constructive scientist voices. The potential
      dialogue could bring us closer to apprehending the simplistic nature of
      multicultural discourses, as well as expose better the reasons why they yield
      such slow results. Namely, we need deeper levels of understanding, and although
      the psychoanalytic approaches to these issues have been often discarded as
      reductionist, only they can orientate us, after making us painfully aware that
      prejudice and tolerance can present themselves side by side, and are not solely
      dependent on the processes of our becoming more conscious and knowledgeable
      citizens. The many scientists that equally engage in stereotyping, testify this
      claim. Thus, this is an insider's meta-narrative that joins the list of present
      approaches that firstly engage in tracing one's own stigmatization processes
      rather than solely deconstructing others.

PMID- 10895531
TI  - The effect of a compulsory curriculum on ethical attitudes of medical students.
AB  - The purpose of the present study was to assess the influence of a compulsory
      curriculum on first-year medical students. The ethical attitude study was
      performed at the School of Medicine, University of Rijeka, Croatia. The samples
      consisted of 171 medical students (68 males and 103 females) interviewed at the
      beginning of the first year of studies. Some of them, namely 143 (56 males and 87
      females) were interviewed again at the end of the same academic year. Data were
      analysed by applying factor analysis under principal component model and varimax
      criterion as the rotation model. The results clearly show that the current
      compulsory curriculum without formal ethical education has a limited influence on
      first-year medical students. That points to the obvious necessity to implement
      the medical ethics in the course of medical education.

PMID- 10895532
TI  - Attitudes, behaviour and knowledge on sexuality among female adolescents in
      Zagreb, Croatia.
AB  - The aim of this study was to estimate the level of knowledge about sexuality,
      attitudes and sexual behaviour of female adolescents. The study included 194
      female students, 117 from Medical High School (MHS) and 77 from General High
      School (GHS) in Zagreb. Data was collected using an anonymous self-administered
      questionnaire. In addition to items on personal data (age, parental education
      etc.), the participants were asked to define terms about sexuality (e.g.
      menstruation, puberty) the definitions of which are found in biology textbooks
      for the fifth and eighth grade of primary school. The aim of the third part of
      the survey was to collect information about attitudes and behaviour of female
      adolescents. The results showed a low level of knowledge in students of both
      schools. General High School students showed a higher level of knowledge than
      their Medical High School peers. One fifth of General High School students and
      1/3 of Medical High School students were unable to define the term
      "menstruation". The majority of adolescents talk about sexuality with their
      friends, 92.1% of General High School and 81.2% of Medical High School students.
      Almost 50% of students of both schools would like to talk about sexuality with
      their school doctor. 6.9% of Medical High School students had at least one sexual
      intercourse while none of the General High School students had been sexually
      active at the time of the survey. As the majority of students were not sexually
      active and results showed a rather low level of knowledge, this seems to be the
      ideal period for the implementation of educational programs aimed at increasing
      the level of knowledge, and thus preventing unwanted consequences (STD,
      pregnancy, abortion, infertility).

PMID- 10895533
TI  - Drug use among Croatian students.
AB  - The subject of this study was to determine the frequency of drug use and
      attitudes toward drug use in Croatian high school students. The study was carried
      out in a middle-class high school in Zagreb. Out of 273 students who participated
      in an anonymous, self-report, 23-item questionnaire, 69 reported that they had at
      least once used drugs. The most frequently used drug was cannabis. While one
      third of students have been offered drugs, even 41% of the students would have
      take the drug if it becomes available. It can be concluded that the drugs appear
      to be highly available among Croatian students. According to our results, even
      more stronger increase in the number of drug users in Croatia could be expected.

PMID- 10895534
TI  - The Croatian Health Survey--SF-36: I. General quality of life assessment.
AB  - The objective of the Croatian Health Survey was the assessment of population
      health related quality of life in the transitional environment of Croatia. Health
      status measures incorporate dimensions such as physical, psychological, and
      social functioning, role performance and perception of wellbeing. In order to
      assess health status, "The medical outcome study 36-item short-form health survey
      (SF-36) model" was used. A total sample of 5048 inhabitants (1983 males and 3065
      females), 18 years and over, represents approximately 1% of the general
      population of Croatia. Mean scores were as follows: physical functioning (PF)
      69.94, role-physical (RP) 63.01, bodily pain (BP) 64.51, general health (GH)
      53.40, vitality (VT) 51.85, social functioning (SF) 72.96, role-emotional (RE)
      72.42, mental health (MH) 61.71 and health transition (HT) 44.79. Results of the
      SF-36 health survey in Croatia are very much like the results in other European
      countries with indication that general quality of life is lower in Croatia.

PMID- 10895535
TI  - Health status as geneologic burden in aging process.
AB  - Knowledge of modern molecular biology is leading to the idea that aging and
      diseases of the aged are two different entities. Healthy life is relatively
      limited by the specific number of chronic conditions which are present more in
      old age. Up to now the idea of aging as a process in relation to the individual,
      organ, tissue, cell or a molecule. There are only few studies on the influence of
      aging within a single family and even less of aging within several generations of
      the same family. Genealogic level is one way of getting into the process of
      family system and aging throughout time. The aim of the study was to determine
      the significance of genealogical burden with regard to the health status in
      examinees with different cognitive capabilities. The difference according to sex
      and age was not significant between the two groups. Health status of the
      examinees proband in both groups showed 34.4% healthy examinees in the group D
      and 65.3% in group G. The difference between the two groups was statistically
      significant. The difference of health status of parents (II. generation) was
      statistically significant in both groups. Morbidity of diseases was not
      statistically significant. Most of the ancestors from the grandmothers and
      grandfathers (III generation) died. (group G--97.5%, group D--100%).
      Statistically significant difference is present among the diseases of the
      circulatory system and those of digestive system in this generation. Data on the
      ancestors of the IV. generation showed that all the relatives died in both
      groups. CONCLUSION: The health status of the examinees with higher impairment in
      the test of cognitive capabilities is worse and they come from the families with
      worse health status.

PMID- 10895536
TI  - The comparison of forensic-psychiatric traits between female and male
      perpetrators of murder or attempted murder.
AB  - The aim of this investigation was to define more clearly specific forensic
      psychiatric characteristics of female murder or attempted murder perpetrators.
      The retrospective method applied was based on the comparison of the data from
      forensic-psychiatric assessments carried out in the Center for Forensic
      Psychiatry, Psychiatric Hospital Vrapce, Zagreb, from 1983 to 1997 (including 70
      female and 70 male subjects--who committed murder or attempted murder). Compared
      with men, female offenders were most often in some way emotionally related to
      their victims, and they were more often victimized themselves before committing
      the crime. In men alcoholism was a more significant circumstantial factor in the
      assessment of their accountability. Psychiatric security measures were more often
      given to male offenders. The intensity of aggression was lower in females than in
      males. This investigation reveals that there are some sex specific forensic
      psychiatric traits of murder or attempted murder perpetrators. The obtained
      results could be of help in everyday forensic-psychiatric practice, both in
      assessments and treatment.

PMID- 10895537
TI  - Gender differences in body build and physiological functions in the adult
      population of Yucatan, Mexico.
AB  - This study, conducted in 1994-95, evaluates differences in body build, blood
      pressure and respiratory functions between sexes and age groups of low
      socioeconomic strata individuals living in Merida, Yucatan, Mexico. The cross
      sectional sample includes 344 males and 320 females, 20-98 years of age divided
      into six age groups (20-29, 30-39, 40-49, 50-59, 60-69 and 70+ years) by sex.
      Differences between age cohorts in height, weight, fatness, systolic blood
      pressure, and most respiratory variables (excluding expiratory reserve volume,
      minute ventilation and respiration rate) are greater among women than in men. The
      more marked secular trend in stature and bigger biological differences between
      age cohorts in women might have its beginning in 19th century when living
      conditions of women were worse than those of men. Only since the last decades of
      20th century, migrations and improvements in living conditions might caused more
      drastic changes in women of low social strata than in men. Results of regression
      analysis show a greater relationship between studied variables in women than in
      men what confirms that women are less sensitive to environmental factors. A
      pattern of changes in minute ventilation (MV) with rising age of the cohorts
      differs between men and women (smaller differences appear in the women's cohort)
      Also a different pattern (MV) is seen in European populations. The latter may
      suggest existence of some adaptational phenomena to the local environment.

PMID- 10895538
TI  - Differential reproductive success and body size in !Kung San people from northern
      Namibia.
AB  - The associations patterns between reproductive success, measured by the total
      number of offspring, number of living offspring and number of dead offspring, and
      parental body size, estimated by stature, body weight and Body mass index, were
      tested in 65 female and 103 male members of a !Kung San population ageing between
      25 and 40 years (x = 30.2 yr.) from northern Namibia. In both sexes a significant
      interaction between fertility patterns and body dimensions was found.
      Nevertheless, the association patterns differed markedly between the two sexes.
      While in males tallness and an improved weight status was associated
      significantly with a higher number of surviving offspring, smaller and lighter
      females had significantly more surviving children. In males a directional
      selection towards increased stature and better weight status is in accordance
      with the well known secular trend of acceleration. In females first of all the
      postpartum changes in body composition and body weight, resulting from exhausting
      infant feeding practices seem to support the maternal depletion hypothesis.

PMID- 10895539
TI  - The effect of high birth weight (400 g or more) on the weight and height of adult
      men and women.
AB  - Three hundred and twenty eight examined adult men and 346 examined adult women
      were macrosomic at birth (4000 g or over). The control group consisted of 564
      adult men and 749 adult women with birth weights of 2500 to 3999 g. Both male and
      female macrosomic babies achieve greater weights and heights in adulthood than
      those in the control group. There are more overweight and obese men in the
      macrosomic group than in the control group and the same is true of the women (p <
      0.001). The mean values of the BMI (body mass index) for the macrosomic adults
      are greater than those for the control group (p < 0.001). Fetal macrosomia is a
      good predictor of the weight and height of adult men and women.

PMID- 10895540
TI  - Chronology, dynamics and period of permanent tooth eruption in Zagreb children
      (Part II).
AB  - The aim of the present paper is to determine the beginning, order, median time,
      termination, dynamics, continuity and intensity of the permanent tooth eruption,
      as well as its calendar, in a sample of Zagreb children. The study included 2768
      children (1398 boys and 1370 girls). All subjects were classified in one-year age
      groups. The continuity of tooth eruption occurs from 5.1 years to 14.97 years,
      i.e., for a period of 9.87 years. Each particular tooth has its own dynamics of
      eruption (V5-V95) which on the average amounts to 4.25 years. The continuity of
      eruption is 10.1 years in boys and 9.8 years in girls. The dynamics of eruption
      is 4.15 years in boys and 4.35 years in girls. A certain asymmetry in eruption
      has been described.

PMID- 10895541
TI  - Change in the inclination of the occlusal plane during craniofacial growth and
      development.
AB  - The aim of this study was to examine the change in the occlusal plane inclination
      that takes place during craniofacial growth relative to various facio-cranial
      reference lines, as well as to find possible differences in means between sexes,
      to determine if there were correlations among variables, and to find out which of
      the parameters were the most reliable in determining the occlusal plane
      inclination. The investigation was carried out on 192 lateral radiographs of
      subjects divided into five age groups. The radiographs were traced and six
      angular roentgencephalometric variables were analysed by using different
      reference lines: cranial base (OLNS), Frankfort horizontal (OLFH), maxillary base
      (OLPL), mandibular base (OLML), anterior face height (OLNM) and posterior face
      height (OLSGO). It could be concluded that the change in occlusal plane
      inclination shows anterior rotation (left profile) during growth. The most
      significant change of the occlusal plane inclination was found using variables
      OLPL, OLFH and OLNS. There were no significant differences according to sex.
      Small but significant correlations were found between all investigated variables,
      except OLML.

PMID- 10895542
TI  - Preventive sealing of dental fissures with Heliosil: a two-year follow-up.
AB  - Due to their shape and configuration of dental crown, especially its biting
      surface with numerous pits and fissures permanent molars are suitable sites for
      retaining food remnants and bacteria. For this reason, preventive efforts and
      early prophylactic procedures should prevent the development of caries at these
      critical sites. Deciduous and permanent teeth of 300 children aged 6-7 years with
      healthy parallel teeth were included in the study. Fissure sealing was performed
      on one side, whereas contralateral teeth served as controls. During a two-year
      period, control examinations with finding recording were performed every six
      months. During the two-year follow-up period, the sealed teeth remained free of
      caries as long as the coating persisted. In deciduous teeth, the sealant was
      first observed to be missing at 18 months in 5%, and at 24 months in 8% of the
      teeth. None of these teeth was affected by caries, suggesting that a part of the
      sealant was retained in the fissures. In permanent teeth, caries developed in 18%
      of the sealed teeth at 24 months.

PMID- 10895543
TI  - Relationship of gastric metaplasia and age, sex, smoking and Helicobacter pylori
      infection in patients with duodenal ulcer and duodenitis.
AB  - Gastric metaplasia is one of the factors in duodenal ulcer appearance. The aim of
      this study was to investigate the frequency of gastric metaplasia and its
      connection with age, sex, cigarette smoking and H. pylori infection. In the study
      216 patients were included. There were 98 patients with duodenal ulcer, 60 with
      duodenitis, and 58 healthy control subjects. There was no statistically
      significant difference in gastric metaplasia frequency according to age and sex.
      Gastric metaplasia was statistically more significant in patients with duodenal
      ulcer (p < 0.01). In all the subjects cigarette smoking did not significantly
      influence gastric metaplasia. In smokers with duodenal ulcer, and those who
      besides duodenal ulcer and smoking had H. pylori infection gastric metaplasia was
      more frequent (p < 0.01). However, in patients with duodenal ulcer, there was no
      statistically significant difference of gastric metaplasia related to H. pylori
      presence. It may be suggested that H. pylori infection is not of indispensable
      significance for gastric metaplasia appearance.

PMID- 10895544
TI  - Left ventricular hypertrophy in obese hypertensives: is it really eccentric? (An
      echocardiographic study).
AB  - In order to study left ventricular hypertrophy patterns in obese hypertensives,
      we examined 132 patients with essential hypertension by 2D, M-mode and Doppler
      echocardiography. The patients were classified in four comparable groups,
      corresponding to the values of Quetelet's body mass index (BMI) and grades of
      obesity. More obese hypertensives had on average larger left ventricles with
      thicker walls and larger left atria than less obese, or lean ones. Left
      ventricular mass increased significantly and progressively with advancing grades
      of obesity, but relative wall thickness (wall thickness/cavity size ratio) did
      not diminish. Doppler echocardiography revealed significantly higher prevalence
      of left ventricular diastolic dysfunction among obese than among lean
      hypertensives. In the second part of our study, we analyzed the subgroups defined
      by the severity of hypertension and the age of the patients. The correlation of
      the indices of left ventricular and left atrial hypertrophy with the BMI values
      was considerably better in the group of moderate than in the group of mild
      hypertension. The r values were 0.62 vs. 0.22 for left ventricular mass and 0.64
      vs. 0.26 for left atrial dimension. The group of patients with severe
      hypertension was characterized by left ventricular cavity enlargement in
      correlation with increasing BMI values, but without corresponding left
      ventricular wall thickening. So called left ventricular "eccentricity index", as
      the reverse value of relative wall thickness, correlated well (r = 0.76) with the
      BMI values. The indices of left ventricular hypertrophy correlated with the BMI
      values slightly better in middle age groups than in the groups of the youngest (<
      or = 30 years) or the eldest (> or = 61 years) hypertensives. In conclusion,
      eccentric left ventricular hypertrophy does not seem to be a distinctive feature
      of hypertensive heart disease in obesity. There is only some tendency toward the
      "eccentricity" of left ventricular geometry which becomes more apparent in more
      severe forms of hypertension, especially in very obese persons.

PMID- 10895545
TI  - Haematological profile in healthy urban population (8 to 70 years of age).
AB  - Haematological profile for 17 constituents of blood were determined in 998
      healthy school children (8-19 years old) and 2246 healthy adult persons (20-70
      years old) residing permanently or at least 5 years in a defined geographic
      region of Zagreb, Croatia. Physiological variations corresponding to age and sex
      were studied as the most important factors affecting biological variation in
      haematological constituents of blood. In our study erythrocytes, haemoglobin and
      haematocrit values were not sex dependent until the age of 13 after which the
      values were higher in men that in women. Sedimentation rate showed sex and age
      related differences in the adult age with higher values in women especially after
      50 years. Total leukocyte count declined with age and in adults the values were
      slightly lower in women. Segmented neutrophil granulocytes showed the upward
      trend with age whereas the lymphocyte and monocyte counts declined. Women showed
      slightly higher platelet count in the adult age. Based on biological variation,
      we have estimated the reference intervals for 17 haematological constituents of
      blood in order to provide medically reliable evaluation of haematological
      laboratory results.

PMID- 10895546
TI  - Haemodynamic changes in patients with whiplash injury measured by transcranial
      Doppler sonography (TCD).
AB  - The daily increasing number of cervical whiplash injuries presents ever-greater
      requirement for vertebrobasilar diagnostics. A cervical spine injury, which is
      quite frequent injury, may occur during a fall, or industrial, traffic, sport or
      war injury. Transcranial Doppler (TCD) sonography with Transcan 3-D EME device
      and 2 MHz probe was used for the assessment of vertebrobasilar circulation in
      patients with a whiplash injury of the cervical spine, that occurred mostly in
      car accident. This study includes 47 patients with clinically verified cervical
      spine trauma with x-ray evidence of no bone lesion. The patients were examined by
      TCD within a month, and then six months following the accident. The obtained
      values were compared to normal blood flow velocities and correlated with the
      severity of clinical picture. During the first month after the injury,
      statistically significant disturbances in the vertebrobasilar circulation were
      recorded, such as the increase in mean blood flow velocities in AVL (68%), AVR
      (62%) and BA (51%) (mostly as spasam). Six months later, normal findings were
      obtained in about 50% of the vessels, whereas in rest of the patients vasospasam
      persisted in one, two or all examined blood vessels. TCD of the vertebrobasilar
      circulation was found to be a very useful method in the diagnostics and follow-up
      of patients with a whiplash injury.

PMID- 10895547
TI  - Value of color-Doppler imaging in diagnosis of intrabulbar and intraorbital
      tumors.
AB  - Patients with intrabulbar and intraorbital tumours have been investigated by
      colour Doppler imaging. In the first group there were 20 patients with malignant
      melanoma of the uvea and in the second group there were 19 patients with
      cavernous hemangioma. The third group was a control group represented by 20
      healthy individuals. In the group of patients with uveal melanoma it has been
      established that every patient, except one, has a blood flow inside of tumour
      tissue. Internal blood flow of intraorbital hemangioma was slower than inside the
      melanoma and the resistance index was lower. Comparison of blood flow in all
      patients has shown that there is no statistically significant difference between
      ophthalmic artery, central retinal artery and posterior ciliary arteries except
      in maximal blood flow in central retinal artery and posterior ciliary arteries.

PMID- 10895549
TI  - System of the performance evaluation criteria weighted per positions in the
      basketball game.
AB  - Based upon the expertise performed by ten basketball professional relative
      importance coefficients with regard to positions in the game were determined for
      nineteen performance evaluation criteria. High degree of interobservers agreement
      was obtained concerning all positions (from 0.91 to 0.98). In concordance with
      the obtained results the particular play positions were explicitly described, as
      well as similarities and differences between them were determined from the aspect
      of the single criteria importance. The following criteria had an above average
      importance for the: Position 1--levels of defensive pressure, transition defense
      efficiency, the ball control, passing skills, dribble penetration, outside shots,
      and transition offence efficiency; Position 2--level of defensive pressure,
      transition defense efficiency, outside shots, dribble penetration, offence
      without the ball, and transition offence efficiency; Position 3--transition
      defense efficiency, outside shots, dribble penetration, offense without the ball,
      free throws, and transition offence efficiency; Position 4--defensive and
      offensive rebounding efficiency, inside shots, dribble penetration, efficiency of
      screening, and free throws; Position 5--defensive and offensive rebounding
      efficiency, inside shots, dribble penetration, efficiency of screening, drawing
      fouls and three-point plays, and free throws. The research results could be
      usefully applied by the basketball practitioners to selecting and following-up
      players, the teching-learning process directing and improving, the training
      process programming and the transformational effects controlling.

PMID- 10895548
TI  - Prognosis for the patients with chronic hepatitis B.
AB  - The purpose of the research was to determine the influence of the hepatitis B
      virus on the progression of the chronic liver disease. In the present paper, 127
      patients who were followed up for five years and who had histologically verified
      chronic liver disease, are described. Fifty two of them were carriers of HBsAg,
      75 patients were HBsAg negative, but had other markers typical for a previous
      infection of HBV in the sera. All the patients were nonalcoholics and no drug
      addicts. In the sera of these 127 patients markers of HBV were prospectively
      followed up: HBsAg, HBeAg, anti-HBs, anti-HBc, anti-HBe, HBVDNA, antiHCV for C
      virus and anti-D for D virus. It was proved by these investigations that HBV
      provokes very severe chronic hepatitis: CAH (chronic active hepatitis) and CH
      (cirrhosis hepatis). It was also proved that HBV replicated in 44.20% patients,
      namely, HBVDNA was positive in the sera of those patients. In 26.08% of such
      patients the mutant form of HBV was present. In spite of progressive liver
      disease and without any antiviral therapy all the patients with chronic HBV
      cirrhosis hepatis were, after five year-follow-up, in Child-Pugh A grade. It was
      found that the patients who were HBsAg negative, but had one or more markers of
      HBV positive in the sera, had also a severe chronic hepatitis. That group of
      patients remains our object of further research. The five-years follow-up of all
      these patients demonstrates that it is necessary to find out an efficient
      medicament against HBV chronic hepatitis. Obligatory vaccination of the risk
      population against virus B remains the only prevention against this severe
      disease.

PMID- 10895550
TI  - Doses in the vicinity of mobile X-ray equipment in a children's intensive care
      unit.
AB  - Most of the patients in the intensive care unit for children are newborns and
      infants having an infection of the central nervous system, with systemic septic
      and respiratory infections. Therefore, mobile X-ray equipment including mobile
      shields is routinely used for diagnosis of the respiratory tract, heart and
      endovascular catheterization. The aim of this work was to determine the radiation
      exposure to the children in the vicinity of the exposed patient in the same or
      next room. Three measurement runs were carried out with thermoluminescence
      dosimetry system. The results show that the homogeneity of the irradiation field
      is adequate, the exposure of children to radiation in the vicinity of the exposed
      patient in the same or next room is very low, practically in the range of the
      lowest detectable dose. The entrance dose on the breast of the patient was found
      to be 0.07 mSv. Therefore, there is no basis for the risk estimation of genetic,
      leukemogenic and cancerogenic detriment.

PMID- 10895551
TI  - Hereditary hemorrhagic telangiectasia or Rendu-Osler-Weber syndrome in the same
      family.
AB  - The authors present the case of three patients from the same family in whom
      hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber syndrome was
      diagnosed. The disease is rare and occurs with multiple telangiectases of the
      skin and mucosa, and pulmonary arteriovenous fistulae. The clinical status of our
      patients included multiple telangiectases of the skin and mucosa, recurrent
      epistaxis, exertion dyspnea and cyanosis. Polycythemia and hypoxemia were
      observed in the blood. The clinical status and conventional radiological
      examination of the thoracic region, with the suspicion of arteriovenous (A-V)
      fistulae, pointed to HHT. A-V fistulae were confirmed by pulmonary angiography.
      The pulmonary A-V fistulae were operated in all three patients and diagnosis was
      confirmed by histopathological examination of the operated samples. Clinical
      improvement was observed after the operation and cyanosis, dyspnea, hypoxemia and
      polycythemia disappeared.

PMID- 10895552
TI  - Prognosis for the patients with alcoholic and nonalcoholic liver disease.
AB  - The purpose of this investigation was to determine the role of alcohol in
      development of progressive liver disease. For this purpose, 41 alcoholic patients
      were followed up for 5 years. Criteria for alcohol abuse was that the patients
      were enjoying 20 g alcohol daily in a period of 5 years for females and
      respectively 60 g daily for males. In the same time a group of 51 nonalcoholic
      patients with histologically proven chronic liver disease were investigated. In
      all 92 patients chronic liver disease and progression of the disease was proven
      by liver biopsy during a 5-years follow-up. In sera of all patients the markers
      of hepatitis viruses B, D and C were continuously determined and chronic viral
      hepatitis was excluded. Also, autoimmune chronic hepatitis was excluded. The
      results of the investigation showed that alcoholics develop cirrhosis hepatitis,
      in most cases 78.04%. The most progressive chronic liver diseases--cirrhosis and
      hepatocellular carcinoma--are significantly present among nonalcoholics (p < or =
      0.05). In the mentioned investigation a large group of 51 patients with severe
      chronic hepatitis without a proven etiology of disease was found and it deserves
      priority in future research.

PMID- 10895553
TI  - Libido and PTSD.
AB  - The most frequent PTSD treatment is group therapy. Experiences gained from this
      kind of work warn us of big difficulties, especially if psychotherapist is an
      analytically oriented person. He has to do with non-presence of insight. These
      groups are dominated by projection and catharsis, which is often a source of
      secondary traumas. However, patients are fond of these group sessions. In the
      dynamics of such group sessions, what can be recognized is the tendency towards
      repression of the actual problems a PTSD patient has in his family, at work and
      in social relations. One of these problems, marked for the intensity of
      repression and negation, is the problem of libido. Weakness of potency and other
      libidinous problems are often the source of family problems as well as auto
      aggressive acts. Libidinous problems are a taboo topic and the task of a
      psychodynamically oriented psychotherapeutist is to point out at this problem.
      Psychotherapeutic process changes its dynamics while directing verbalization to
      the problem of libido. Apart from readiness for solving the problem, patients
      with PTSD diagnosis show an interest in the members of their family being
      involved into psychotherapy. A special dynamics is being developed while solving
      the libidinous problems of the widows whose husbands were killed in war.

PMID- 10895554
TI  - In memoriam. Mirko Drazen Grmek (1924-2000).

PMID- 10895555
TI  - Strategies used with intrusive thoughts: a comparison of OCD patients with
      anxious and community controls.
AB  - Models of intrusive thoughts attribute a key role to strategies used by people to
      cope with their unwanted cognitions. In an extension of previous work, the
      authors conducted structured interviews with 38 people with obsessive-compulsive
      disorder, 38 people with another anxiety disorder, and 19 healthy volunteers. The
      interview identified the repertoire of strategies used with the participant's
      most troubling thought. The 2 clinical groups reported significantly more
      strategies than the nonclinical group. The clinical groups also reported
      significantly greater intensity of the thought and their emotional response and
      lower efficacy for the strategies. People with OCD reported a significantly
      higher proportion of strategies that were specifically linked to the thought
      content (as distinct from nonspecific strategies that were only linked
      sequentially in time). The results identify both common and differential
      characteristics of intrusive cognition in anxiety disorders.

PMID- 10895556
TI  - Coping with Gulf War combat stress: mediating and moderating effects.
AB  - The authors examined relationships between method of coping with combat-related
      stress and psychological symptoms among Gulf War Army personnel (N = 1,058).
      Participants were surveyed on return from the Gulf region (Time 1) with the
      Coping Responses Inventory (R. Moos, 1990) and a measure of combat exposure.
      Outcomes were symptom measures of posttraumatic stress disorder (PTSD) and
      depression. At Time 2 (18-24 months) participants completed the same symptom
      measures and an index of postwar stress. Higher proportions of approach-based
      coping in the war zone were related to lower levels of psychological symptoms.
      Combat exposure moderated the effects of coping on Time 1 PTSD. Coping predicted
      changes in symptoms of depression but not PTSD. Combat exposure affected changes
      in depression through postwar stress but had a direct negative effect on PTSD.

PMID- 10895557
TI  - Mood and alcohol consumption: an experience sampling test of the self-medication
      hypothesis.
AB  - In this investigation the authors applied the experience sampling method to
      prospectively test the self-medication hypothesis. In vivo reports gathered in
      the context of daily life demonstrated that nervousness was the only negative
      mood state to predict increases in alcohol consumption later in the course of the
      day. Further examination of this within-person relationship demonstrated that men
      were more likely to consume alcohol when nervous than were women, but this
      association was unrelated to family history of alcoholism, problem drinking
      patterns, or trait anxiety and depression. Consistent with the self-medication
      hypothesis, cross-sectional analyses also confirmed that alcohol consumption was
      generally associated with lower levels of nervousness; this effect varied by
      several demographic and clinical variables. These findings are discussed in terms
      of the diversity of reasons for alcohol consumption and their potential for
      explaining problem drinking.

PMID- 10895558
TI  - War zone stress, personal and environmental resources, and PTSD symptoms in Gulf
      War veterans: a longitudinal perspective.
AB  - Cross-sectional research has demonstrated a link between personal and
      environmental resources and development of emotional distress after war zone
      service. Less is known about the longitudinal relationship between resources and
      distress. The authors addressed this issue in a study of 348 Gulf War returnees
      tested at 2 time points. Resources decreased and posttraumatic stress disorder
      (PTSD) symptoms increased over time. Time 1 avoidance and family cohesion
      predicted PTSD symptoms at Time 2. Regression analyses revealed a bidirectional
      relationship over time between resources and PTSD symptoms. Time 1 resources
      predicted Time 2 psychopathology after accounting for Time 1 emotional distress.
      PTSD symptoms at Time 1 also predicted changes in coping and family
      relationships, even after accounting for Time 1 resources. Findings are
      consistent with the concept of a loss spiral (Hobfoll, 1989), in which resource
      factors and emotional sequelae to war stress exert reciprocal effects.

PMID- 10895559
TI  - Directed forgetting of emotional stimuli in borderline personality disorder.
AB  - On the basis of clinical literature, the authors hypothesized that individuals
      with borderline personality disorder (BPD) would show biased information
      processing when they were exposed to negative affective stimuli of a particular
      type. Individuals with BPD and controls were tested using a directed forgetting
      paradigm. Study participants were exposed to 3 types of words (borderline,
      neutral, positive) and were cued to either remember or forget each word as it was
      presented. There were no group differences on a free recall task for words in the
      remember condition. However, participants with BPD recalled significantly more of
      the borderline words from the forget condition than did controls. In other words,
      borderline participants remembered borderline words that they were instructed to
      forget. These results may be consistent with enhanced encoding of salient words
      and perhaps related themes in BPD individuals.

PMID- 10895560
TI  - A longitudinal study of high scorers on the hypomanic personality scale.
AB  - Former college students (n = 36) identified by high scores on the Hypomanic
      Personality Scale (HYP; Eckblad & Chapman, 1986) were compared with control
      participants (n = 31) at a 13-year follow-up assessment. As hypothesized, the HYP
      group reported more bipolar disorders and major depressive episodes than the
      control group. The HYP group also exceeded the control group on the severity of
      psychotic-like experiences, symptoms of borderline personality disorder, and
      rates of substance use disorders. HYP group members with elevated scores on the
      Impulsive-Nonconformity Scale (Chapman et al., 1984) experienced greater rates of
      bipolar mood disorders, poorer overall adjustment, and higher rates of arrest
      than the remaining HYP or control participants.

PMID- 10895561
TI  - The external validity of Asperger disorder: lack of evidence from the domain of
      neuropsychology.
AB  - The present study compared individuals with high-functioning autism (HFA) and
      Asperger disorder (AD) in intellectual, motor, visuospatial, and executive
      function domains. Participants with AD demonstrated significantly higher Verbal
      and Full Scale IQ scores, significantly larger Verbal-Performance IQ
      discrepancies, and significantly better visual-perceptual skills than those with
      HFA. Once the superior intellectual abilities of the AD group were controlled
      (both statistically through analysis of covariance and by examining IQ-matched
      subgroups of HFA and AD participants), no significant group differences in motor,
      visuospatial, or executive functions were evident, save a marginally significant
      trend toward poorer fine motor performance in the AD group. This suggests that AD
      may simply be "high-IQ autism" and that separate names for the disorders may not
      be warranted. The relation of these findings to theories of autism and AD are
      discussed.

PMID- 10895562
TI  - Age differences in genetic and environmental influences on eating attitudes and
      behaviors in preadolescent and adolescent female twins.
AB  - A sample of 680 11- and 602 17-year-old female twins was used to examine (a) age
      differences in genetic and environmental influences on disordered eating
      attitudes and behaviors and (b) associations between body mass index (BMI) and
      eating attitudes and behaviors. Univariate, biometrical model-fitting analyses
      indicated that 11-year-old twins exhibited less genetic and greater shared
      environmental influence on eating attitudes and behaviors than 17-year-old twins.
      Bivariate model-fitting analyses indicated that the relationship between BMI and
      eating attitudes was mediated primarily by common shared environmental influences
      in 11-year-old twins and common genetic influences in 17-year-old twins.
      Nonetheless, the majority of genetic influences on eating attitudes and behaviors
      in older twins were due to genetic effects that are independent of those
      operating in BMI.

PMID- 10895563
TI  - Neuropsychological functioning in nonreferred siblings of children with attention
      deficit/hyperactivity disorder.
AB  - The goal of this study was to assess neuropsychological functioning in
      nonreferred siblings of children with attention deficit/hyperactivity disorder
      (ADHD). Participants were 156 siblings of ADHD probands with (N = 40) and without
      (N = 116) ADHD (according to criteria of the Diagnostic and Statistical Manual of
      Mental Disorders (3rd edition, revised; American Psychiatric Association, 1987)
      and 118 siblings of non-ADHD normal controls of similar age, IQ, and grade level.
      Information on attention, executive, and memory functions was obtained in a
      standardized manner without knowledge of clinical status. Compared with siblings
      of controls, siblings with ADHD were significantly impaired on the Stroop test
      and on verbal learning and memory. In contrast, siblings without ADHD were
      similar to controls on virtually all measures. These data suggest that some
      executive, attention, and verbal learning deficits are found in nonreferred
      individuals with ADHD but that neuropsychological deficits are unlikely to
      constitute an endophenotype to ADHD.

PMID- 10895564
TI  - Schizophrenia outpatients' perceptions of their parents: is expressed emotion a
      factor?
AB  - The factors that mediate the association between expressed emotion (EE) and
      relapse in schizophrenia patients are still unknown. Many researchers hypothesize
      that interactions with high-EE individuals are stressful for patients, leaving
      them vulnerable to relapse. It would be useful to investigate whether patients
      perceive interactions with high-EE parents as stressful. In this study,
      associations were examined between levels of EE in parents and the types of
      personal memories patients had about these parents. EE ratings were obtained for
      both parents of 27 schizophrenia outpatients, and patients were asked to describe
      "happy, nonstressful" memories and "unhappy, stressful" memories during 2
      interviews. Patients recounted fewer nonstressful memories and more stressful
      memories about high-versus low-EE parents. Implications of these results are
      discussed.

PMID- 10895565
TI  - Nightmares and bad dreams: their prevalence and relationship to well-being.
AB  - This study, for the first time, distinguishes between nightmares and bad dreams,
      measures the frequency of each using dream logs, and separately assesses the
      relation between nightmares, bad dreams, and well-being. Eighty-nine participants
      completed 7 measures of well-being and recorded their dreams for 4 consecutive
      weeks. The dream logs yielded estimated mean annual nightmare and bad-dream
      frequencies that were significantly (ps < .01) greater than the mean 12-month and
      1-month retrospective estimates. Nightmare frequency had more significant
      correlations than bad-dream frequency with well-being, suggesting that nightmares
      are a more severe expression of the same basic phenomenon. The findings confirm
      and extend evidence that nightmares are more prevalent than was previously
      believed and underscore the need to differentiate nightmares from bad dreams.

PMID- 10895566
TI  - Unconscious memory bias in depression: perceptual and conceptual processes.
AB  - Mood-congruent memory (MCM) bias in depression was investigated using 4 different
      implicit memory tests. Two of the implicit tests were perceptually driven, and 2
      were conceptually driven. Depressed participants and nondepressed controls were
      assigned to 1 of 4 implicit memory tests after studying positive and negative
      adjectives. Results showed no MCM bias in the perceptually driven tests. MCM was
      demonstrated in 1 of the conceptually driven tests, but only for adjectives that
      were conceptually encoded. Results support the theory that mood-congruent
      processes in depression are limited to conceptual processing. However, activation
      of conceptual processes may not be sufficient for demonstrating mood congruency.

PMID- 10895567
TI  - De novo conditioning in trauma-exposed individuals with and without posttraumatic
      stress disorder.
AB  - Differential conditioning was assessed in 15 medication-free individuals meeting
      Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American
      Psychiatric Association, 1994) criteria for chronic posttraumatic stress disorder
      (PTSD) and 18 trauma-exposed individuals who never developed PTSD (non-PTSD).
      Conditioned stimuli (CSs) were colored circles, and the unconditioned stimulus
      was a "highly annoying" electrical stimulus. Individuals with PTSD had higher
      resting heart rate (HR) and skin conductance (SC) levels and produced larger SC
      orienting responses. During conditioning, the PTSD group showed larger
      differential SC, HR, and electromyogram responses to the reinforced vs.
      nonreinforced stimuli (CS+ vs. CS-) compared with the non-PTSD group. Only PTSD
      participants continued to show differential SC responses to CS+ vs. CS- during
      extinction trials. Results suggest that individuals with PTSD have higher
      sympathetic nervous system arousal at the time of conditioning and are more
      conditionable than trauma-exposed individuals without PTSD.

PMID- 10895568
TI  - Predictors of time to remission from depression in primary care patients: do some
      people benefit more from positive life change than others?
AB  - The authors examined the role of personality, social support, and coping
      strategies and their interaction with positive life change (PLC) in influencing
      time to remission from depression in 86 depressed primary care patients (69%
      women, mean age = 36.6 years), who were followed for 3.5 years. Diagnostic
      information was obtained by the Present State Examination (J. K. Wing, J. Cooper,
      & N. Sartorius, 1974), and life change by the Life Events and Difficulties
      Schedule (G. W. Brown & T. O. Harris, 1978). The association of PLC and other
      predictors with the time to remission was studied by means of Cox regression. PLC
      reduced time to remission in women, but not in men. Other predictors that
      expedited remission were low severity of premorbid difficulties, high self
      esteem, and a tension-reducing coping style. Neuroticism modified the effect of
      PLC in that the remission forward bringing effect of PLC was stronger for highly
      neurotic people. The results suggests that women and psychologically vulnerable
      persons benefit most from PLC.

PMID- 10895569
TI  - Evaluating gene x psychological risk factor effects in the pathogenesis of
      anxiety: a new model approach.
AB  - The present study evaluated the singular and interactive effects of a functional
      polymorphism (variation) in the serotonin transporter (5-HTT) gene and a
      psychological trait (anxiety sensitivity [AS], i.e., fear of arousal symptoms) in
      predicting subjective and physiological responses to a 35% carbon dioxide (CO2)
      challenge in a community sample (N = 72). Genotypes were divided into 2 groups in
      accord with prior research. Findings were partially supportive of the
      hypothesized risk model. These indicated that the Group L genotype (homozygous
      for the 1 allele), compared with the Group S genotype (homozygous for the s
      allele plus heterozygous individuals), predicted greater fearful response to the
      biological challenge. There was also an AS x Genotype interaction predicting
      heart rate variability (HRV) in response to the CO2, suggesting that high AS plus
      Group L status predicts decreased HRV.

PMID- 10895570
TI  - Comprehension of televised stories in boys with attention deficit/hyperactivity
      disorder and nonreferred boys.
AB  - Two studies compared comprehension of televised stories by 7- to 12-year-old boys
      with attention deficit/hyperactivity disorder (ADHD) and nonreferred comparison
      boys. Boys watched one show with toys present and one with toys absent. Visual
      attention was continuously recorded, and recall was tested after each show.
      Across studies, visual attention was high with toys absent but decreased sharply
      with toys present for boys with ADHD. Groups showed similar levels of cued recall
      of discrete units of information regardless of differences in attention. When
      recall tasks and television story structure required knowledge of relations among
      events, the reduced attention of boys with ADHD interfered with recall. Although
      visual attention of comparison boys also decreased to some extent with toys
      present, there was no such decrement in recall. Implications of the difficulties
      children with ADHD have in integrated story comprehension are discussed.

PMID- 10895571
TI  - Autobiographical memories in women remitted from major depression.
AB  - Several studies show that depressed people tend to overgeneralize when asked to
      recall autobiographical memories (AM); in particular, they respond with categoric
      descriptions. The authors sought to find out whether this tendency also occurs
      after remission from depression. Two groups of women who were not depressed at
      the time of the study were compared; only 1 group had a history of major
      depression. With an AM test, women in remission from major depression retrieved
      significantly more categoric descriptions when responding to negative cue words
      than women without a major depression in their biography. These findings support
      the assumption that AM is a correlate and a consequence of depression.

PMID- 10895572
TI  - The importance of callous-unemotional traits for extending the concept of
      psychopathy to children.
AB  - This study focused on the use of callous-unemotional (CU) traits to identify a
      subgroup of children with both attention deficit/hyperactivity disorder (ADHD)
      and a conduct problem diagnosis (oppositional defiant disorder [ODD] or conduct
      disorder [CD] who show characteristics similar to adults with psychopathy. In a
      clinic-referred sample of children aged 6 to 13 years (N = 154), those with
      diagnoses of both ADHD and ODD/CD were divided on the basis of teacher ratings of
      CU traits. Children high on these traits showed features typically associated
      with psychopathy, such as a lack of fearfulness and a reward-dominant response
      style. Furthermore, children with CU traits seemed less distressed by their
      behavior problems. These findings are consistent with research on adults showing
      that impulsivity and antisocial behavior alone are insufficient to document
      persons who fit the construct of psychopathy.

PMID- 10895573
TI  - A prospective study of psychophysiological arousal, acute stress disorder, and
      posttraumatic stress disorder.
AB  - This study investigated the role of acute arousal in the development of
      posttraumatic stress disorder (PTSD). Hospitalized motor-vehicle-accident
      survivors (n = 146) were assessed for acute stress disorder (ASD) within 1 month
      of the trauma and were reassessed (n = 113) for PTSD 6 months posttrauma. Heart
      rate (HR) and blood pressure (BP) were assessed on the day of hospital discharge.
      Participants with subclinical ASD had higher HR than those with ASD and no ASD.
      Participants who developed PTSD had higher HR in the acute posttrauma phase than
      those without PTSD. Diagnosis of ASD and resting HR accounted for 36% of the
      variance of the number of PTSD symptoms. A formula composed of a diagnosis of ASD
      or a resting HR of > 90 beats per minute possessed strong sensitivity (88%) and
      specificity (85%) in predicting PTSD. These findings are discussed in terms of
      acute arousal and longer term adaptation to trauma.

PMID- 10895574
TI  - Clinical implications of "subthreshold" depressive symptoms.
AB  - There is active debate regarding whether diagnosable depression exists on a
      continuum with subthreshold depressive symptoms or represents a categorically
      distinct phenomenon. To address this question, multiple indexes of dysfunction
      (psychosocial difficulties, mental health treatment history, and future incidence
      of major depression and substance abuse/dependence) were examined as a function
      of the extent of depressive symptoms in 3 large community samples (adolescent,
      adult, and older adult; N = 3,003). Increasing levels of depressive symptoms were
      associated with increasing levels of psychosocial dysfunction and incidence of
      major depression and substance use disorders. These findings suggest that (a) the
      clinical significance of depressive symptoms does not depend on crossing the
      major depressive diagnostic threshold and (b) depression may best be
      conceptualized as a continuum. Limitations of the present study are discussed.

PMID- 10895575
TI  - [Summer, sun, UV risks. Health during sunbathing].

PMID- 10895576
TI  - [The gambler--you patient?. Interview by Dr. Brigitte Moreano].

PMID- 10895577
TI  - [Coronary heart disease: grave deficiencies in secondary prevention. Almost no
      one is concerned with blood lipids].

PMID- 10895579
TI  - [Hypertension in pregnancy].

PMID- 10895578
TI  - [Peptic ulcer in the elderly--endoscopy in suspected ulcer. Therapy always
      includes proton pump inhibitor].
AB  - In the elderly patient, peptic ulcer disease is associated with increased
      morbidity and mortality. Abdominal pain is often absent, and the first sign is
      blood in the stools. The major risk factors are infection with Helicobacter
      pylori and the use of non-steroidal antiinflammatory drugs (NSAIDs). Endoscopic
      and medical treatment of peptic ulcer is independent of the age. The use of
      proton pump inhibitors is the treatment of choice. In the event of an infection
      with H. pylori, eradication treatment is usually carried out. Currently, however,
      H. pylori eradication is not recommended in patients with NSAID-associated
      ulcers; if possible, the NSAIDs should be discontinued. The development of a new
      generation of NSAIDs holds out the promise of a marked reduction in
      gastrointestinal side effects.

PMID- 10895580
TI  - ["Panorama images" with ultrasound. A computer program joins individual images to
      make a continuous image].
AB  - SieScape is a novel method that enables the investigator to obtain continuous
      ultrasonographic images of extensive structures. Its ease of use and rapidity of
      deployment make SieScape the method of choice for the documentation and
      monitoring of large superficial lesions, for example hematomas following arterial
      puncture. With the aid of Color Sie Scape, not only views can be obtained in any
      desired plane, but also the relationship of the hematoma to the vascular
      structures can be documented.

PMID- 10895581
TI  - [Pain therapy. Value of unconventional methods].

PMID- 10895582
TI  - [Vasodilating beta blockers as effective antihypertensive agents. Results of a
      multicenter observational study].

PMID- 10895583
TI  - [Vasculitis syndrome. 1: Introduction].

PMID- 10895585
TI  - [Sequelae of the integration process].

PMID- 10895584
TI  - [Dyspnea in infarct diagnosis. Myocardial perforation with contrast medium
      extravasation into the pericardium].

PMID- 10895586
TI  - [In occupational disease and occupational accidents. How independent are expert
      witnesses?].

PMID- 10895587
TI  - [This EBM will reach its goal: it really is not meant to function. Interview by
      Werner Loosen].

PMID- 10895588
TI  - [Pilot project in general practice. Early flu warning via the internet].

PMID- 10895589
TI  - [Clinico-pharmacologic 24-hour action. Distally active diuretics better than loop
      diuretics].

PMID- 10895590
TI  - [When there is a risk for fractures. No time limit for fluorides].

PMID- 10895591
TI  - [Mobilization to control heart and cerebral infarct].

PMID- 10895592
TI  - [Prevention of thromboembolism. Which internal medicine patients are at risk?].

PMID- 10895593
TI  - [Sunlight exposure and skin cancer].

PMID- 10895594
TI  - [Give them a pill?].

PMID- 10895595
TI  - [Sunbathing habits and risk of melanoma].
AB  - The increasing frequency of malignant melanoma (MM) is believed mainly to be due
      to the habit of sunbathing, which has an impact on the skin due to ultraviolet
      radiation, especially if intermittent and causing sunburn. Frequent use of
      tanning booths possibly increases the risk of MM but the question has not been
      settled. Use of sunscreens has a certain prophylactic effect on actinic
      keratoses, but no documented effect on MM. This does not imply that sunscreens
      are not advisable, but stresses the importance of correct use of sunscreens
      together with other sun protective measures. Primary prevention of MM is mainly a
      question of minimizing the impact of ultraviolet radiation (including tanning
      booths) on the skin: limit time in the sun, cover up with clothing, and use a
      sunscreen with a protection factor of at least 15.

PMID- 10895596
TI  - [Dermatoscopic diagnosis of cutaneous malignant melanoma. Secondary prophylaxis].
AB  - During the last four decades the incidence of malignant melanoma has increased
      seven fold. Clinically, it is often difficult to distinguish malignant melanoma
      from a benign naevus. The macroscopic clinical ABCD rule and the Glasgow 7-point
      checklist are didactically helpful, but inaccurate with many false positive and
      negative diagnoses. Dermatoscopy performed by a trained physician has increased
      the diagnostic accuracy to a sensitivity of 89% and specificity of 80% (meta
      analysis of 11 studies). The dermatoscopic ABCD rule and the Risk Stratification
      method (RS) are reviewed.

PMID- 10895597
TI  - [Treatment of bipolar depression with antidepressive agents--a dilemma].

PMID- 10895598
TI  - [Roller skating accidents--the pattern of injuries and use of protective devices.
      Roller skating accidents in Viborg 1995-1998].
AB  - Circumstances and outcome of roller skating accidents (RSA) and the use of
      protective gear was surveyed. During 1.1.95-31.12.98 a questionnaire survey was
      conducted among subjects involved in RSA and combined with data from the A + E
      dept. A major increase in RSA was reported during this four year study period. A
      total of 399 injuries were recorded, of which 178 had wrist-related injuries and
      of which 125 had fractures. RSA accounted for a total of 17% of all wrist
      fractures among 11-15 year-old teenagers. In 1998 this percentage had increased
      to 28%. The median age for wrist fracture was 12.6 years. Of the 325 injured who
      answered the questionnaire, 67% (mostly children) did not use any kind of
      protective gear, and only 64% had purchased such gear. Beginners and experienced
      skaters showed differences regarding characteristics and risk profile. Education
      in non-risk behaviour and the recommendation of wrist guards seems permissible,
      as the number of injured is suspected to be steadily growing among teenagers.

PMID- 10895600
TI  - [Socioeconomic costs due to tobacco smoking].
AB  - The objective of the study was to calculate costs attributable to smoking from
      both a societal and a public finance perspective. The Cost-of-Illness analysis
      was based on incidence data from 1995 and 1996, estimated with the attributable
      fraction, based on English and Danish RR-estimates respectively. The indirect
      costs are calculated with both the friction and the human capital method. In
      1995, smoking attributable costs in Denmark amounted to 4100 million DKK with the
      friction method and based on Danish RR-estimates, including 3600 million in
      direct costs and 500 million in indirect costs. A public cash flow analysis
      showed a net revenue of about 3900 to 5600 million DKK. Compared with previous
      results for Denmark (1983), the annual costs to society increased by about 118%.
      It is suggested that similar Cost-of-Illness analyses are carried out at regular
      intervals to monitor the economic consequences of smoking in society.

PMID- 10895599
TI  - [Roller skating accidents. A registry and questionnaire study].
AB  - At the University Hospital of Odense DK an increasing number of roller skating
      injuries has been observed, and a total of 283 injuries were registered in 1996.
      They all received a questionnaire in order to obtain information about: The
      differences between users of conventional and in-line roller skaters in pattern
      of injury, to what extent safety gear was used and occurrence of "splint-top"
      fractures. Eighty-seven percent were returned. It showed that "in-liners" and
      conventional roller skaters showed no statistical differences in pattern of
      injury. Accidents occurred at low speed. Twenty-nine percent used protective
      gear. There was a significantly lower rate of injuries to the hand and wrist when
      wrist guards were used. Splint-top fractures were not observed. Increasing
      experience seems to lower the incidence of fractures. An increase in the use of
      protective gear seems to occur following an injury.

PMID- 10895601
TI  - [Dementia and pseudodementia in the municipality of Ringkobing].
AB  - Social services estimated on September 1, 1997 that 221 individuals out of a
      population of about 16,000 in the whole of Ringkobing County were believed to
      suffer from dementia. Citizens believed to suffer from dementia were offered an
      assessment by a trained nurse and a general practitioner. In the following six
      months, 119 people were screened by the nurse with the Mini Mental State
      Examination, the Geriatric Depression Scale-15 and Gottfries-Brane-Steen scale
      for evaluating functional deficiencies in demented patients. In addition, somatic
      and laboratory screening was done by the GP's. Approximately 40 citizens or 33%
      were not found to suffer from dementia but suffered from other illnesses. One
      year later all the GP's answered questionnaires concerning number of cases of
      depression, hypothyroidism, vitamin B12 deficiency or other illnesses not earlier
      known to the GP. Twenty-two diseases were identified and six patients improved.

PMID- 10895602
TI  - [Planned second-look gastroscopy in patients with bleeding ulcer].
AB  - Preliminary studies have suggested a beneficial effect of second look endoscopy
      in patients with bleeding peptic ulcer. We have performed a retrospective survey
      of 70 patients with bleeding peptic ulcer admitted to our department. Planned
      second look endoscopy and repeated sclerotherapy was standard care. We found 15
      of the 70 patients to rebleed after initial sclerotherapy. Overall success rate
      of endoscopic therapy was 63/70 patients (90%). The most important factor
      predicting rebleeding was the occurrence of active bleeding at the initial
      endoscopy. Compared with an expected rebleeding rate derived from the literature
      of 20-25 patients, the present study suggests a beneficial effect on rebleeding
      rate of planned second look endoscopy. Future controlled trials should verify
      this hypothesis.

PMID- 10895603
TI  - [Periostal interposition in epiphysiolysis, diagnosed by ultrasound].
AB  - Musculoskeletal ultrasound is a rapidly expanding diagnostic field. High
      frequency transducers with high spacial resolution make it possible to
      demonstrate superficial soft tissue structures such as tendons, muscles,
      ligaments and even, under certain circumstances, fractures and periosteum. A case
      is presented where ultrasound clearly visualised periostal interposition in a
      distal tibial epiphysiolysis in an eight year-old boy, and some aspects of
      ultrasound in musculo-skeletal imaging are discussed.

PMID- 10895604
TI  - [The wandering gastrostomy tube].
AB  - A case is described in which a patient with a gastrostomy tube (PEG) was admitted
      to hospital with chronic and severe diarrhoea and signs of cachexia. The
      gastrostomy tube had been inserted by percutaneous endoscopic procedure two
      months before, and the patient had been suffering from diarrhoea ever since. X
      ray investigation by contrast documented that the PEG ended inside the colon, at
      the left colic flexure. The case emphasizes the need to control the position of a
      PEG, should unexpected gastrointestinal symptoms occur.

PMID- 10895605
TI  - [Picture of the month. Ectopic intrathecal thyroid tissue].

PMID- 10895606
TI  - [Recombinant human TSH].

PMID- 10895608
TI  - [HUGO--an attempt to correct a widely spread misunderstanding].

PMID- 10895607
TI  - [Aging and antioxidants].

PMID- 10895609
TI  - [What happens with Yersinia in agriculture?].

PMID- 10895610
TI  - Changing concepts of decorum and allure in the representation of teeth in art.
AB  - During the twentieth century western attitudes towards facial beauty have been
      transformed by developments in modern dental science. The possibility not only of
      retaining one's own teeth in adulthood, but also improving their appearance,
      changing the position, shape and colour, altering the contours of the face,
      eliminating deformity through different kinds of surgery--all of these
      astonishing developments have brought about a fundamental change in the way we
      see the human face, and how we expect it to look back at us. This paper
      illustrates the extent of the transformation of western attitudes towards facial
      beauty in the twentieth century by examining the ways artists have represented
      or, more frequently, concealed teeth in European painting and sculpture at key
      points since the sixteenth century. It examines some traditional prejudices
      (which still flourished in Victorian Britain, for example) against the open
      display of teeth, long regarded as threatening, indecent, at times lurid, rarely
      beautiful. It explores the widespread belief that rotten teeth were synonymous
      with moral corruption. It assesses the impact of modern media upon recent and
      quite radically different canons of beauty--the twentieth-century emphasis upon
      facial symmetry, for example, a concept foreign to the European portrait
      tradition--and concludes by examining a unique collaboration between artists,
      patients and maxillofacial surgeons currently taking place in the Cleft Palate
      Unit at Guy's Hospital in London, a project organized by the Ruskin School of
      Drawing at Oxford University.

PMID- 10895611
TI  - Interdisciplinary dentofacial therapy (IDT): a comprehensive team approach.
AB  - Modern dentistry, with its various disciplines, has an exciting and unmatched
      potential to enhance the overall quality of life for our patients. In this
      environment one of the greatest challenges for clinicians is to properly utilize
      this vast potential. It can be very difficult to consistently establish health
      and physiological occlusal relationships in patients with significant dental,
      periodontal, dentoalveolar, temporomandibular, and/or skeletal problems. This
      task is further complicated by ever-increasing patient and provider demands for
      results with optimal dentofacial aesthetics and long-term stability.
      Interdisciplinary Dentofacial Therapy (IDT) is a proven diagnostic and clinical
      pathway for consistently maximizing patient outcomes in these complicated areas.
      Within a climate of increasing scientific and technological advances in
      dentistry, today's dental professional must study continuously to stay abreast in
      one area, let alone in all of them. The responsibility to the patient, however,
      is to utilize fully the extensive options that the profession can provide. As
      stated above, a proven treatment philosophy for accomplishing this is called
      Interdisciplinary Dentofacial Therapy, or IDT. When properly performed, IDT can
      produce unparalleled professional satisfaction and camaraderie by reaching higher
      levels of patient care through optimal coordination of knowledge and skills in
      the various disciplines. In addition, IDT can consistently produce optimal
      treatment results while simultaneously producing profound practice management,
      time management and marketing benefits for practitioners. This paper briefly
      describes these benefits while defining the philosophies and hallmarks of IDT. It
      will also give insight into the implementation of IDT and why it will be even
      more necessary and valuable in the future than it is today.

PMID- 10895612
TI  - A common sense approach to TMJ and implant imaging.
AB  - During the last two decades, computer-based imaging technology has contributed
      significantly to our assessment of patients with head and neck anomalies. For
      instance, magnetic resonance imaging has given us a modality for visualizing the
      hard and soft tissues of the temporomandibular joint. We are fortunate that this
      has led to the refinement of the concepts of normality and the characterization
      of non-normal conditions. In the pre-surgical assessment of alveolar bone prior
      to implant placement, tomography in its various forms has provided the
      possibility of three dimensional bony assessment thus potentially optimizing
      fixture placement and minimizing potential failure. Unfortunately, there has been
      a reluctance to employ these techniques as they are either not available or both
      the equipment and the cost of image acquisition time is too expensive. Until
      recently, there has been a lack of consensus as to the selection of imaging
      modalities appropriate to patient presentation and the clinical value of the
      information obtained. The more recent development of computer-controlled
      panoramic imaging has made available to us many special projections which are
      capable of producing hard tissue images of either the TMJ or a potential implant
      site in multiple dimensions at lower cost (both financially and in terms of X-ray
      dose) than the more advanced modalities. These projections can now be
      incorporated into a clinically determined patient-based protocol and thus provide
      the clinician with both an economical and common sense approach to diagnostic
      imaging.

PMID- 10895614
TI  - A general review of the p53 gene and oral squamous cell carcinoma.
AB  - Oral cancer has increased recently in Australia, and overall survival rates have
      not improved in the past 30 years. Dentists are uniquely well placed to screen
      their patients at regular recall examinations and detect cancers or pre-cancerous
      lesions at an early curable stage. Although the major risk factors--tobacco
      smoking and alcohol abuse--have been identified, only a minority of patients at
      risk will develop oral cancer. Molecular analysis has now detected an
      accumulation of genetic lesions in oral cancer, but the earliest molecular
      changes in the oral epithelium in the progression to malignancy in at-risk
      patients has not yet been determined. These changes could if known be exploited
      for screening purposes. How long human oral carcinogenesis takes to progress from
      the initiated cell to an invasive tumour, and whether molecular biology can be
      used to identify the minority of patients who will develop cancer from the large
      population exposed to the risk factors, are other important unanswered questions.
      p53 tumour suppressor gene mutations are the most frequently found genetic errors
      in oral cancer and the p53 gene is a likely target for tobacco and alcohol.

PMID- 10895613
TI  - The use of systemic antibiotics in dental practice.
AB  - Clinical dental practice is immersed in the primary treatment and corrective
      management of infectious bacterial diseases of the oral and peri-oral region.
      Systemic antibiotics play a key role in achieving either therapeutic and/or
      prophylactic treatment goals. There are a number of theoretical considerations
      associated with the use of systemic antibiotics in dental practice. These are
      related to the principles of infection management, microbiology and host
      response, and the pharmacology of the particular agent. In the clinical setting,
      these principles are modulated by a number of factors. These factors need to be
      understood to ensure appropriate prescribing of antibiotics. Minimizing the
      occurrence of antibiotic misuse and abuse has global implications for the
      containment of resistant bacterial strains. This paper discusses some of the
      current understanding of prescribing practices by dentists. Also presented is an
      outline of the factors that may be considered in the use of antibiotics.

PMID- 10895615
TI  - Endodontic treatment: what can and what can't be saved.
AB  - Although endodontic treatment is generally considered to have a high success
      rate, not all teeth provide an opportunity for predictable salvage by endodontic
      therapy and subsequent restoration. New studies are yielding valuable information
      about factors that affect the outcome of treatment, which enhances the ability of
      the clinician to make a more accurate preoperative assessment and improve the
      quality and predictability of treatment. Most teeth can be saved by endodontic
      treatment; however, some cases fail despite good treatment. How can we assess and
      predict the outcome of treatment? This paper reviews reasons for biological
      failure of endodontic treatment and describes clinical factors that influence
      whether you might treat, refer, or extract the tooth.

PMID- 10895616
TI  - Implants: success and failure--a literature review.
AB  - There has been increased emphasis within the literature regarding the ailing
      (treatable) and failing (non-treatable) implant. This review will describe
      current literature regarding the criteria for implant failure and explains what
      factors influence the likelihood of failure. Failure mechanisms can be divided
      into those occurring prior to, and after osseointegration. Progressive peri
      implant bone loss together with a soft tissue inflammatory lesion can be defined
      as peri-implantitis, and is a major cause of failure after osseointegration.
      Regular maintenance of implants is critical to monitor the peri-implant situation
      for early detection of the signs of implant failure. More research is required
      involving diagnostic parameters in the early recognition of implant failure.

PMID- 10895617
TI  - Periodontics and its influence on aesthetics.
AB  - The gingival tissues form the soft tissue frame of the dentition and play an
      important role in dental aesthetics in the maxillary anterior region of the
      mouth. Alterations to the form and symmetry of the gingivae through
      developmental, pathologic or iatrogenic factors can significantly alter the
      appearance and harmony of the natural dentition or prosthetic tooth replacement.
      This paper describes the techniques available for the management of gingival
      recession and for surgical lengthening of the clinical crown with particular
      emphasis on diagnosis and case selection.

PMID- 10895618
TI  - Some principles in the selection and use of some tooth-coloured materials and
      techniques--1998.
AB  - In an era when many clinicians are confused or almost overwhelmed by the rapidity
      of change in the field of conservative dentistry, the purpose of this
      presentation/paper is to identify briefly, with 'bottom line' statements, the
      research evidence in many topics within this field. The fields to be covered are
      glass ionomer restorations, 'compomer' restorations, composite resins, 'posterior
      composites', post-restoration sensitivity, direct pulp therapy, resin bonding to
      enamel and to dentine.

PMID- 10895619
TI  - A new classification and techniques for simple restorative dentistry.
AB  - It is nearly one hundred years since G. V. Black proposed a simple, five-stage
      classification for carious lesions based upon the site of the lesion and the type
      of restorative material likely to be used for restoration. In the absence of both
      effective preventive measures and a knowledge of remineralization his approach
      was essentially surgical: having identified a lesion remove it surgically, as
      well as all surrounding susceptible tooth structure, to prevent recurrence.
      Surgery is no longer regarded as the primary choice for treatment of a disease
      and there are many factors which suggest that this system is out of date.
      Preservation of natural tooth structure should be the principal aim and this is
      best achieved through remineralization. Remaining cavitated areas can then be
      restored more conservatively, thus assisting in maintaining aesthetics as well as
      strength in the tooth crown. If the profession is to adopt a new approach to
      operative dentistry it is suggested that the psychology of introducing a new
      classification for carious lesions is a desirable move.

PMID- 10895620
TI  - Rhinoplasty in achieving total facial harmony.
AB  - Surgical alteration of the nose has challenged surgeons for decades and
      rhinoplasty is often described as one of the most difficult aesthetic procedures
      to master. As in the case of planning the orthognathic patient, there is a blend
      of aesthetic and functional goals. While patients may primarily present for
      cosmetic reasons, the maintenance of functional nasal airways in the pursuit of
      an improvement in facial balance is essential. It is the purpose of this paper to
      present the assessment and management of common nasal deformities, some of which
      are integrated within simultaneous orthognathic surgery.

PMID- 10895621
TI  - A modified approach to the Le Fort II osteotomy.
AB  - A modified technique of Le Fort II osteotomy is described for the correction of
      naso-maxillary hypoplasia. The surgical access was via a combination of bicoronal
      flap and transoral sulcular incision. Any periorbital skin incision is avoided.
      This is made possible by having the medial orbital cut made through the lacrimal
      groove. The anterior limb of the medial canthal ligament is detached, but leaving
      the posterior and superior limbs intact. Following mobilization, the osteotomy
      segment is stabilized by miniplates without intermaxillary fixation. This method
      eliminates the need for facial incision and hence the residual scar. Patients'
      recovery and acceptability of this modified approach to Le Fort II osteotomy is
      much enhanced.

PMID- 10895622
TI  - The effects of zygomatic and chin augmentation on facial aesthetics.
AB  - The most obvious and prominent parts of the facial anatomy which affect
      aesthetics are the nose, the prominence of the zygoma and the chin. These three
      structures are extremely important when assessing facial aesthetics, and whilst
      basal structures of the maxilla and mandible are important, it is the positioning
      of the zygoma, nose and chin which ultimately are the determining factors of good
      facial aesthetics. This paper outlines the various methods of zygomatic and chin
      augmentation and describes the intra-oral approach to performing an osteotomy of
      the zygoma. These procedures are commonly performed in association with
      orthognathic surgical procedures to correct the occlusion and can be carried out
      primarily with the initial surgery, or secondarily for aesthetic enhancement.

PMID- 10895623
TI  - A review of myeloproliferative disease with presentation in the head and neck
      region.
AB  - The diagnosis of an essential thrombocytosis is demonstrated in this presentation
      of a well-looking 53 year old man who had a five-year history of increasing
      facial asymmetry as evidenced by deviation of his mandible to the right and
      malocclusion. The enlarged mandibular condyle was the first manifestation of his
      underlying myeloproliferative disorder. His management will be discussed.
      Neoplastic diseases of the multipotent haematopoietic stem cells result in four
      major diseases: chronic myelogenous leukaemia (CML); polycythaemia vera (PV);
      agnogenic myeloid metaplasia with myelofibrosis (AMM/MF); essential
      thrombocytosis (ET). CML: demonstrates increased production of neutrophils and
      marked splenomegaly. It is divided into a chronic phrase typified by hyperplasia
      of mature bone marrow elements and a blastic or acute phase which evolves into a
      proliferation of immature marrow elements and can develop into acute myelogenous
      leukaemia. PV: associated with increased production of all myeloid cells but
      dominated by increased red blood cells with splenomegaly. AMM/MF: allows the
      neoplastic stem cells to proliferate and lodge in multiple sites outside the bone
      marrow. Splenomegaly and fibrosis of marrow spaces also occurs. ET: resulting in
      a markedly elevated platelet count in the absence of a recognizable stimulus.
      Treatment revolves around measures to maintain hydration, to relieve arthralgias,
      to prevent thrombotic episodes, and to prevent infections.

PMID- 10895624
TI  - The use of bone grafts and substitutes in the craniomaxillofacial region.
AB  - Craniomaxillofacial defects arise from congenital abnormalities or are acquired
      following trauma or ablative surgery. Various bone grafting techniques have been
      developed for application in the facial skeleton to assist in the reconstruction
      of small alveolar deficiencies to more complex, extensive bony defects.
      Autogenous grafts from different sites vary in volume, stability and contour
      characteristics. The introduction of allogeneic grafts has further increased the
      possibilities for hard tissue replacement as have alloplastic substitutes which
      have been used successfully. Recent advances in bone regeneration in the
      maxillofacial region using distraction osteogenesis and the recent advent of cell
      culture techniques have introduced new therapeutic approaches that will provide
      the foundation for a significant shift in the approach to reconstructive surgery
      of the facial skeleton.

PMID- 10895625
TI  - An overview of aesthetic surgery of the face.
AB  - This article explores the interface between the aesthetic aspects of dentistry
      and complementary cosmetic surgery of the face. Dentists do not often think of
      facial cosmetic surgery and plastic surgeons do not often think of aesthetic
      dentistry as being complementary to their endeavours. This paper is designed to
      help breach this gap. An outline is given of the various cosmetic surgery
      procedures used on the face with emphasis on those in the perioral region.
      Procedures discussed include meloplasty, blepharoplasty, laser resurfacing,
      liposculpture, lip augmentation, rhinoplasty, chin augmentation, correction of
      prominent ears, and skin care.

PMID- 10895626
TI  - International oral and maxillofacial surgery: the medical/dental interface.
AB  - Oral and maxillofacial surgery is a unique specialty based in dentistry but
      requiring extensive surgical training. The vast proliferation of medical and
      dental knowledge has resulted in extreme pressure on educational processes in
      both professions and, as a result, current medical graduates have little
      knowledge of dentistry and dental education has suffered with a reduction in
      teaching in medical and surgical disciplines. The specialty of oral and
      maxillofacial surgery has become the referral base for a wide variety of the
      surgical and pathological problems in the maxillofacial region. The specialty,
      therefore, finds itself in a position where its expertise in specialty procedures
      is frequently poorly understood by both medical and dental colleagues. There is a
      need for strong international cooperation in order to maintain a viable
      monospecialty without fragmentation. This must include coordinated training
      programmes placed on the now widely accepted guidelines for training and
      education adopted by the International Association of Oral and Maxillofacial
      Surgeons.

PMID- 10895627
TI  - The interface between United Kingdom, Irish and Australasian college
      qualifications.
AB  - Colleges in different parts of the world fulfil an important role in setting
      standards and ensuring a high calibre of postgraduate dental education and
      training. They have evolved to fulfil the requirements of the particular
      circumstances prevailing in each country. With the changes that are taking place
      throughout the world and the increasing demands for high quality general and
      specialist dental care, all of the colleges are modifying their structures and
      examination formats. In many ways these changes are bringing the colleges more in
      line with each other. In view of this, there is a need for better communication
      and closer collaboration between the colleges. In the United Kingdom and Ireland
      proposals for shorter, more structured training programmes and for more
      specialist dental care to be provided outside hospitals, together with the
      influence of European Community law, have resulted in major changes. Among the
      effects of these changes are a restructuring of training programmes, the
      development and recognition of new specialties and the reconfiguration of college
      qualifications.

PMID- 10895628
TI  - Radiological features of osteogenic sarcoma of the jaws. A comparative study of
      different radiographic modalities.
AB  - OBJECTIVE: To evaluate the clinical and radiological features of osteogenic
      sarcoma of the jaws with particular reference to the effectiveness of the
      radiographic modalities used. MATERIAL AND METHODS: A total of 66 cases (57 from
      the English-language literature and nine new cases) were critically evaluated for
      the features depicted with intra-oral and panoramic radiography and CT. RESULTS:
      The mean age of the patients was 36 years (median 31.5 years). There were no
      differences in gender distribution. A ratio of 1:1.6 between the maxilla and the
      mandible was found. Lesions had diffuse borders in 78% of cases and defined but
      not corticated borders in 22%. Twenty-nine per cent were radiolucent, 29%
      radiopaque and 41% mixed density. Widening of the periodontal ligament space
      (PDL) was seen in 14 of the 47 (28%) lesions associated with teeth and structural
      changes in the mandibular canal in 34% of the mandibular lesions. There was a
      periosteal reaction in 48% and soft tissue involvement in 33% of the lesions.
      CONCLUSIONS: Widening of the PDL space was best demonstrated on periapical
      radiographs. Structural changes in the mandibular canal were shown mainly with
      panoramic radiographs. Periosteal reaction was best demonstrated by occlusal
      radiographs and soft tissue involvement by CT. Thorough radiological examination
      using periapical, occlusal and panoramic radiography, and recognition of the
      radiological features of osteogenic sarcoma should lead to earlier diagnosis.

PMID- 10895629
TI  - Mail survey of dental radiographic techniques and radiation doses in Greece.
AB  - OBJECTIVES: To measure the entrance dose from periapical radiography in Greece
      and to determine the relative influence of factors affecting it. METHODS: Special
      packs, containing a questionnaire, a film (X-Omat MA 18 x 22.4 cm, Ready Pack,
      Kodak-Pathe, Paris, France) with an attached aluminium stepwedge and a pre
      exposed Ektaspeed Plus (Kodak) film, were mailed to 550 randomly selected dental
      practitioners. The results were tested statistically using an Analysis of
      Variance (level P < 0.05). RESULTS: Three hundred and sixty-four packs were
      returned: 311 were complete but in 53 the pre-exposed film had not been
      developed. The average HVL was 1.4 mm Al 51% of the units had pointed cones and
      34% a beam diameter larger than 6 cm. 54% of the dentists used E-speed films.
      Eighty per cent of the films were inadequately processed. For the total group the
      average entrance dose was 6.9 mGy (range 0.6-36 mGy), and 6.3 mGy (range 0.6-35
      mGy) for the completed packs (n = 311). The radiation dose for the completed
      packs was significantly influenced by HVL, film speed, length of cone and
      standard of processing. CONCLUSIONS: HVL, film speed, length of cone and
      standards of processing influence the entrance dose. Not all of the available
      measures for reducing radiation dose are commonly practised in Greece. Continuing
      education programs can help to improve radiation safety for dental patients.

PMID- 10895630
TI  - Validation of spiral computed tomography for dental implants.
AB  - OBJECTIVES: To investigate the accuracy of 2DCT orthoradial reformatted images
      from spiral computed tomography (CT) for pre-surgical planning of dental implants
      in proximity to the mental foramen. METHODS: Eight cadaver heads were imaged by
      spiral CT (S/Xpress, Toshiba-America, Tustin, CA) with 1 mm thick axial slices by
      1 mm/sec of table feed. The image data set was transferred to a networked
      computer workstation. Using computer graphics the data was analysed with 2D
      orthoradial reformatting using the ToothPix (Cemax, Fremont, CA, USA) protocol.
      Linear measurements were made by two oral radiologists independently from the
      superior border of the mental foramen to the crest of the alveolar process and
      from the inferior border of the mental foramen to the mandibular inferior border.
      The soft tissues were removed and physical measurements made using a 3 Space
      (Polhemus, Colchester, VT) electromagnetic digitizer with a personal computer
      running Windows 95. RESULTS: The differences between the measurements on
      orthoradial 2DCT images and the physical measurements were not statistically
      significant (P > 0.05). CONCLUSIONS: Two-dimensional spiral CT imaging allows
      highly accurate measurements for dental implant placement in proximity to the
      mental foramen. Computer graphics software, using reformatted reconstruction, is
      suitable for implant planning.

PMID- 10895631
TI  - Computed tomography in the diagnosis of maxillofacial mass lesions in younger
      children.
AB  - OBJECTIVE: To evaluate the CT findings of maxillofacial mass lesions in younger
      children and to discuss the effectiveness of CT in their differential diagnosis.
      PATIENTS AND METHODS: CT findings of 17 patients (age range, 0 years 5 months to
      3 years 3 months) with histopathologically proven maxillofacial mass lesions were
      retrospectively evaluated. About two-thirds (11/17) comprised congenital lesions
      or more common lesions in infancy or younger children. RESULTS: Hemangiomas,
      dermoid cysts and ranulas in this age group presented characteristic CT findings
      in common with those occurring in adults. Two invasive lesions (melanotic
      neuroectodermal tumor and aggressive fibromatosis) had irregular margins and the
      latter also showed aggressive bone destruction. Two angiomas had irregular
      margins. A fibrosarcoma showed expansile bone destruction but had a regular
      margin. CONCLUSION: CT was useful in demonstrating the extent of maxillofacial
      mass lesions in children and for surgical treatment planning. Although some
      invasive lesions could be correctly diagnosed on the basis of CT, its diagnostic
      value in differentiating malignant from benign maxillofacial lesions in younger
      children was limited.

PMID- 10895632
TI  - Radiographic study of the mental foramen in a selected Saudi population.
AB  - OBJECTIVES: To determine the most common position of the mental foramen in a
      selected Saudi population and to compare the results with those reported for
      other populations. METHODS: Four hundred and fourteen panoramic radiographs of a
      Saudi population from four different dental centres were studied. RESULTS: The
      commonest position of the mental foramen was in line with the longitudinal axis
      of the second premolar (45.3%) followed closely by location between the first and
      second premolars (42.7%). The mental foramen was symmetrical in 80% of patients.
      CONCLUSION: Clinicians should expect to find the position of the mental foramen
      to be symmetrical and in line with the second premolar teeth.

PMID- 10895633
TI  - Quantitative analysis of spiral computed tomography for craniofacial clinical
      applications.
AB  - OBJECTIVE: To determine the relative accuracy of craniofacial measurements
      obtained from volumetric spiral computed tomography (CT) in two-dimensional (2D)
      and three-dimensional (3D) reconstructions. MATERIALS AND METHODS: Nine cadaver
      heads were examined with spiral CT at 3 mm collimation with 2 mm/s table feed.
      The CT data, stored on optical disks to allow full retrospective review of any
      image, were transferred to a networked computer workstation for off-line
      visualization, measurement and analysis. Three-dimensional surface images (3DCT)
      were generated from spiral CT scans (2DCT). Measurements (n = 28) were made from
      (both unique and conventional craniometric anatomical) landmarks (n = 23)
      identified in 2DCT and 3DCT images by two observers twice. The soft tissues were
      then removed from the cadavers and the measurements performed with an
      electromagnetic digitizer. RESULTS: The accuracy for 3DCT was higher than 2DCT
      images for seven of 28 measurements. Twenty five per cent of the 2DCT
      measurements were found to be significantly different from the physical
      measurements. All measurements with 3DCT were found to have satisfactory accuracy
      in comparison with physical measurements. CONCLUSIONS: Three-dimensional spiral
      CT can distinguish craniofacial anatomy more accurately with some measurements.

PMID- 10895634
TI  - Sources of radiographic distortion in conventional and computed tomography of the
      temporal bone.
AB  - OBJECTIVES: To identify those bony regions of the glenoid fossa where, due to the
      inclination, there is an increased risk of radiographic distortion in
      conventional and computed tomography (CT). METHODS: The inclination of the roof
      and posterior wall of the glenoid fossa was determined relative to established
      imaging planes. Measurements were performed on 50 corrected coronal MR and 50
      axial CT images and 200 sagittal cryosections of 50 temporomandibular joints
      (TMJs). The location of regions with unfavourable bone wall inclination was
      identified using the condyle as a reference. RESULTS: The inclination of parts of
      the fossa roof exceeded the limit for reliable depiction in corrected sagittal
      and coronal planes in 40% and 8% of the joints respectively. The inclination of
      parts of the posterior wall of the fossa exceeded the limit for reliable
      depiction in corrected sagittal and in true sagittal planes in 100% and 84% of
      the joints respectively. In 84% of the joints the inclination exceeded the limit
      for reliable depiction in the axial plane. For both bone walls the regions with
      unfavourable inclination were in the medial part of the joint. CONCLUSIONS: The
      angulation of parts of the roof and posterior wall of the glenoid fossa in
      relation to established imaging planes makes them highly susceptible to
      distortion. The oblique coronal projection is well suited for depiction of the
      roof of the fossa and preferable to a sagittal projection. An oblique axial
      projection is required for the posterior wall.

PMID- 10895635
TI  - Implementation of an oral and maxillofacial radiology image management and
      communication system.
AB  - OBJECTIVES: To implement an oral and maxillofacial radiology image management and
      communication system (OMFR IMACS) in the School of Dentistry, National Taiwan
      University. METHODS: An OMFR IMACS has been implemented over 3 years in three
      phases: (1) Establishment of an OMFR image processing laboratory for research and
      graduate student training; (2) Installation of network infrastructure and (3)
      Total system integration. RESULTS AND CONCLUSIONS: Intraoral, panoramic,
      cephalometric, and TMJ radiographs are directly processed with digital image
      acquisition devices or are converted into a digital format for viewing via UTP
      cable through FastEthernet in the eleven different divisions of the school. The
      system archives about 400 Mb of imaging data daily, representing 80% of the
      workload of the OMFR Division. The system is now used parallel to the
      conventional film-library system and has been integrated as part of the oral
      health service.

PMID- 10895636
TI  - Juvenile ossifying fibroma of the mandible. An 8 year radiological follow-up.
AB  - An 8-year follow-up of a juvenile ossifying fibroma in the left mandible of a 4
      year-old boy is presented. The case demonstrated initial lack of radiological
      evidence of demarcation and subsequent eccentric enlargement, selective tooth
      displacement and a multilocular appearance in areas of active growth. An
      aneurysmal bone cyst and a decrease in the bone content was present in the
      excision specimen.

PMID- 10895637
TI  - Thrombosed varix in the submandibular space.
AB  - Thrombosed varix in the oral region often appears as a pigmented mass in the
      mucosa simulating a hemangiomatous lesion. It rarely occurs in the deeper
      orofacial region. We report a case of thrombosed varix in the submandibular space
      with symptoms of a tumor. The clinical symptoms and MRI and CT findings are
      discussed. The clinical symptoms were not characteristics. High signal intensity
      on CT (80 HU) and a concentric signal distribution on CT and MRI may suggest a
      thrombosed varix.

PMID- 10895639
TI  - Linear occlusion.

PMID- 10895638
TI  - Sydney Blackman 1898-1971. A pioneer of panoramic radiography.

PMID- 10895640
TI  - Neurosensory changes following orthognathic surgery.
AB  - Much variability exists among studies of neurosensory disturbance following
      facial surgery. This diversity of findings may be a function of the different
      surgical procedures and measurement methods used. The present study compared 3
      methods of assessing neurosensory loss following surgical orthodontics. Two
      objective tests and 1 subjective test were administered to 24 patients
      preoperatively and 4 weeks postoperatively. These included measures of 2-point
      discrimination, pressure-pain thresholds, and perceived sensation changes in
      specific facial regions. Postoperatively, all patients needed greater separation
      on the 2-point discrimination test in the lower facial regions, but not in the
      upper regions. Bilateral sagittal split osteotomy patients, especially males,
      required greater separation on these lower sites. Pressure-pain thresholds were
      not significantly impaired in most patients. Those who underwent combined
      maxillary and mandibular procedures experienced lower thresholds on the lower
      lip, while bilateral sagittal split osteotomy patients reported lower thresholds
      on the upper lip. The 2-point discrimination test was consistent with patients'
      self-ratings of neurosensory problems using facial maps, but the pressure-pain
      test was not. The majority of patients reported changed sensation in the lower
      facial regions postoperatively, regardless of surgery type. Examiners were less
      likely to rate these same facial regions as different in sensory acuity. Male
      patients were more likely to report sensory loss or pain postoperatively. These
      findings suggest that self-reports of neurosensory change following orthognathic
      surgery are consistent with tests of 2-point discrimination and somewhat higher
      than examiner ratings, but the objective test of pressure-pain thresholds in this
      study was least sensitive to neurosensory changes.

PMID- 10895641
TI  - Neurosensory function after sagittal split osteotomy of the mandible: a
      comparison between subjective evaluation and objective assessment.
AB  - A large variety of neurosensory testing modalities have been used to evaluate
      skin sensitivity of the lower lip and chin after sagittal split osteotomy of the
      mandible. In this study we compared purely clinical impressions of the
      sensitivity of the lower lip and chin with objective assessments of it. The
      examination modalities included visual analogue scale, light-touch perception,
      and perception thresholds of warm and cold temperatures. The results indicate
      that there is a relatively good positive correlation between subjective
      evaluation and objective assessment of the sensitivity of the lower lip and chin
      after sagittal split osteotomy of the mandible.

PMID- 10895642
TI  - The optical surface scan as an alternative to the cephalograph for soft tissue
      analysis for orthognathic surgery.
AB  - The aim of this study was to compare cephalographs and optical surface scanner
      images (lasergraphs) by measuring the lipincisor relationship, the nasolabial
      angle, nasal tip projection, the nasofacial angle, the nasomental angle, and the
      labiomental angle in pre- and postoperative orthognathic surgery patients. The
      results showed that the methods were comparable, but the optical surface scan
      (lasergraph) could be used to greater advantage for pre- and postoperative
      assessment of soft tissue changes with orthognathic surgery, because of its
      clarity and 3-dimensional potential.

PMID- 10895643
TI  - Prediction of soft tissue profiles in orthodontic surgery with the Dentofacial
      Planner.
AB  - Since the early 1990s, there have been continuous improvements in the software
      available for planning orthognathic surgery. This study investigates the
      precision of profile prediction by version 1.51 of the Dentofacial Planner (DFP).
      Orthognathic operations in 40 patients with different types of dysgnathia were
      evaluated. The preoperative and postoperative lateral cephalograms were analyzed
      in the DFP. The computer profiles were simulated on the basis of the skeletal
      alterations of the jaws observed postoperatively. The predicted soft tissue
      profiles were compared with the postoperative profile lines and evaluated
      statistically. The quality of the soft tissue prediction varied from one profile
      region to another. Significant differences were shown in various operation
      categories. Appreciable prediction errors were observed in the lip region. In
      particular, the upper lip revealed inadequate protrusion in bimaxillary
      operations. The smallest number of significant errors was found in single-jaw
      operations on the mandible. Significant features were not shown in the chin
      prediction profile, especially caudal to the superior labiomental furrow. The DFP
      version tested in the investigation shows some improvements in the convenience of
      the application compared to the previous versions. The profile prognosis is
      satisfactory, even in complicated bimaxillary operations. Results continue to be
      unsatisfactory in the lip profile prognosis. Further development of the software
      is necessary.

PMID- 10895644
TI  - A comparison of the perception of facial profile by the general public and 3
      groups of clinicians.
AB  - Orthodontists and maxillofacial surgeons frequently plan orthognathic treatment
      to produce an "ideal" Class I occlusion and skeletal relationship. The aim of
      this study was to investigate whether the preferred facial profile chosen by
      orthodontists, maxillofacial surgeons, dental students, and members of the
      general public conformed to a Class I profile. Photographs were taken of 2 male
      and 2 female adult subjects with Class I profiles, and by means of a computer
      program the images were manipulated to produce Class II, Class III, and long face
      profiles. The orthodontists, surgeons, dental students, and members of the
      general public ranked each group of 4 photos in order of their attractiveness.
      Orthodontists and maxillofacial surgeons were found to be significantly more
      likely to choose a Class I skeletal relationship as the most attractive profile.
      A significant difference was found between orthodontists and dental students (P <
      0.01) and between orthodontists and the general public (P < 0.001) with regard to
      the assessment of the Class I profile as the most attractive, when all 4 subjects
      were considered. Similar results were noted for maxillofacial surgeons. Whether
      the assessor was an orthodontist, maxillofacial surgeon, or a member of the
      general public was found to be significant when examining subjects 1 (female) and
      3 (male). The sex of the assessor was also a significant factor for subject 3
      (male), where female assessors were more likely to rank the Class I profile as
      most attractive (P < 0.05).

PMID- 10895645
TI  - Long-term stability of anterior segmental maxillary osteotomy.
AB  - The long-term stability of anterior segmental maxillary osteotomy was evaluated
      in 11 patients. Both the Wunderer and down-fracture procedures were used. The
      patients were examined periodically until 18 months after surgery. Operative and
      postoperative cephalograms were compared; a more reliable method was utilized to
      assess the displacement of the osteotomy segment. Linear and angular measurements
      were used for evaluation of relapse. No major complications were recorded, and no
      correlation was found between the magnitude of segment repositioning and degree
      of relapse. Positional changes at the end of the study, though statistically
      significant, were clinically acceptable and subjectively undetectable. Results
      emphasized the merits and potential of the surgical osteotomy. Satisfactory
      correction of anterior maxillary excess was achieved, with absolute improvement
      in esthetics and occlusion.

PMID- 10895646
TI  - Bimaxillary orthognathic surgery in a patient with long face: a case report.
AB  - The primary characteristics of long face patients are gummy smile and/or anterior
      open bite. Consequently, correction of esthetic and functional problems are
      especially important for long face patients. Since orthodontic therapy alone is
      not sufficient to solve the problem, orthognathic surgical approach is indicated
      for these patients. In this report, orthognathic surgical therapy of a severe
      long face patient with similar findings was presented. Following clinical and
      cephalometric examination and preoperative orthodontic therapy, a Le Fort I
      osteotomy, a bilateral sagittal split osteotomy, and vertical and horizontal
      reduction genioplasties were performed. Alternative surgical therapies,
      complications, and the effects on the upper respiratory tract are also discussed.

PMID- 10895647
TI  - The nasal frame osteotomy: technical note.
AB  - In the practice of orthognathic surgery, a patient presenting with a gummy smile
      and lip incompetence is readily diagnosed as having vertical maxillary excess,
      and a maxillary impaction osteotomy is usually the proposed treatment. If a short
      nose, an arched and upwardly displaced upper lip, and a broad face accompany
      these 2 features, nasal lengthening and caudal repositioning of the central
      portion of the upper lip by a nasal frame osteotomy should be considered instead.
      The technique of the nasal "frame" osteotomy, which was used in 1 patient with a
      4-year follow-up, is described.

PMID- 10895648
TI  - Modified sagittal split ramus osteotomy with a reciprocating saw and new
      retractors.
AB  - Modified sagittal split ramus osteotomy with new instruments and a reciprocating
      saw is reported. With this modification, the sagittal separation of the ramus is
      performed by the reciprocating saw with an original wide-blade buccal retractor
      and a new lingual retractor, instead of the traditional channeled retractor. The
      wide-blade retractor is inserted to the buccal aspect of the mandibular ramus,
      which ensures protection from instrumental injury to the adjacent soft tissues
      and vessels, and the new lingual retractor, instead of the channeled retractor,
      is inserted to the lingual aspect of the ramus. The osteotomy line follows that
      of Dal Pont's modification. Close attention must be paid to the direction of the
      saw blade. The separated bone plane should be located in the external cortical
      bone layer of the ramus, so as to avoid injury of the inferior alveolar
      neurovascular bundle. The osteotomy is completed with the smooth osteotomized
      interface, which facilitates positioning of the bone segments by the surgeon. The
      new instruments and the reciprocating saw may provide safe and rapid sagittal
      split ramus osteotomy.

PMID- 10895649
TI  - Stepwise overjet reduction with a modified twin-block appliance.

PMID- 10895650
TI  - Chairside technique for the eruption of ectopic maxillary molars.

PMID- 10895651
TI  - A fan-shaped maxillary expander.

PMID- 10895652
TI  - Maxillary molar distalization with a modified pendulum appliance.

PMID- 10895653
TI  - Bilateral transposition of maxillary canines to the incisor region.

PMID- 10895654
TI  - A computerized tooth-width analysis.

PMID- 10895655
TI  - Loss of anterior torque control due to variations in bracket slot and archwire
      dimensions.

PMID- 10895656
TI  - An impacted central incisor with a severe root malformation.

PMID- 10895657
TI  - Ideal appliance placement with APC brackets and indirect bonding.

PMID- 10895659
TI  - Efficacy of open-bite treatment with the Thera-spoon. Correction

PMID- 10895658
TI  - The Spring Jet for slow palatal expansion.

PMID- 10895660
TI  - 1999 JCO Orthodontic Practice Study. Part. 3. Practice growth and other
      variables.

PMID- 10895661
TI  - Dr. Junji Sugawara on the skeletal anchorage system. Interview by Dr. Larry W.
      White.

PMID- 10895662
TI  - Technique clinic. Custom-fit plastic chin cup.

PMID- 10895663
TI  - Lingual lever-arm technique for en masse translation in patients with generalized
      marginal bone loss.

PMID- 10895664
TI  - A new appliance for orthopedic correction of Class III malocclusion.

PMID- 10895665
TI  - A simple method of determining the bite-opening effect of posterior extrusion.

PMID- 10895666
TI  - Nitinol total control: a new orthodontic alloy.

PMID- 10895667
TI  - 1999 JCO Orthodontic Practice Study. Part. 1. Trends.

PMID- 10895668
TI  - Butterfly expander for use in the mixed dentition.

PMID- 10895669
TI  - A comparison of three digital cameras for intraoral photography.

PMID- 10895670
TI  - Prevention of gagging with a modified Krol's method.

PMID- 10895672
TI  - JCO roundtable on ethics in orthodontic practice. Part. 6. Correction

PMID- 10895671
TI  - An orthodontic appliance used in management of lingual focal dystonia.

PMID- 10895673
TI  - Effective taper criterion for the full veneer crown preparation in preclinical
      prosthodontics.

PMID- 10895674
TI  - Long-term reliability of semiadjustable articulator interchangeability.
AB  - PURPOSE: Interchangeability between articulators allows mounted casts to be
      accurately transferred from one articulator to another. The purpose of this study
      was to evaluate the interchangeability of Whip-Mix model #2240 articulators (Whip
      Mix Corporation, Louisville, KY) that had been in clinical use for between 1 and
      6 years. MATERIALS AND METHODS: Forty-six Whip-Mix model #2240 articulators that
      had been in clinical use by students, practitioners, or laboratory technicians
      for between 1 and 6 years were evaluated for interchangeability using the Whip
      Mix #2245 check system. The horizontal tolerance of the check system was 94
      microns. The articulators were also evaluated in the vertical dimension at four
      locations around the check system cylinders using 26-micron shimstock. Vertical
      discrepancies between the cylinders were recorded as the thickness of 0, 1, 2, or
      more than 2 pieces of shimstock. RESULTS: Thirty-eight of the articulators (83%)
      passed the test for interchangeability. These articulators were interchangeable
      with other Whip-Mix model #2240 articulators fabricated over a 5 1/2-year period
      (December 1990 to August 1996). In the vertical dimension, most articulators had
      discrepancies < or = 26 microns. Three articulators (6.5%) had vertical
      discrepancies greater than 52 microns. CONCLUSIONS: (1) Eighty-three percent of
      Whip-Mix model #2240 articulators that had been in clinical use for between 1 and
      6 years remained interchangeable within a tolerance of 94 microns in the
      horizontal dimension. (2) Only three articulators in this study (6.5%) had a
      vertical discrepancy at any location between the cylinders greater than 52
      microns. (3) The model #2240 articulator has the potential to remain
      interchangeable during clinical use.

PMID- 10895675
TI  - Comparison of sectioning rates among carbide and diamond burs using three casting
      alloys.
AB  - PURPOSE: This study compared the sectioning rates of commercially available high
      noble, noble, and base metal casting alloys using two new cross-cut tungsten
      carbides specifically manufactured for alloy sectioning and two medium grit
      diamond burs. MATERIALS AND METHODS: Rectangular bars cast from a base metal
      alloy (Ni-Cr-Mo-Be), a noble alloy (Pd-Cu-Au), and a high noble alloy (Au-Ag-Cu
      Pd) were sectioned under controlled conditions. Two types of cross-cut tungsten
      carbide and two types of medium grit diamond burs were tested using a high-speed
      handpiece under a coolant flow rate of 20 mL/min and an applied load at the bur
      tip of 0.9 N (91.5 g). Three 4-mm cuts were made through the alloy specimens
      using six burs of each type. The time required for Cuts 1, 2, and 3 was recorded,
      and sectioning rates in millimeters per minute were calculated as a relative
      measure of cutting efficiency. For each alloy, the total time required for the
      three cuts was analyzed using one-way analysis of variance (one-way ANOVA) and
      Scheffe tests (alpha = 0.05) to determine differences in sectioning rate among
      bur types. RESULTS: In general, mean sectioning rate for Cut 1 through Cut 3
      decreased with longer use of the bur. Regarding total sectioning times, the
      carbide burs sectioned the base metal alloy significantly faster (P < .001) than
      the diamond burs. However, diamond burs sectioned the high noble alloy
      significantly faster (P < .001) than the carbide burs. Diamond burs also
      sectioned the noble alloy more quickly than the carbide burs, but the difference
      was not statistically significant. CONCLUSIONS: The cross-cut tungsten carbide
      burs should be used to section the base metal alloy but the medium grit diamond
      burs should be used to section the high noble alloy.

PMID- 10895676
TI  - Effect of toothbrushing on elemental release from dental casting alloys.
AB  - PURPOSE: This study assessed the effect of toothbrushing on the elemental release
      from common dental casting alloys. MATERIALS AND METHODS: A Au-Pt high-noble
      alloy, a Au-Pd high-noble alloy, a Pd-Cu-Ga noble alloy, and a Ni-Cr base-metal
      alloy were placed into a biological medium for 1 week to allow equilibration of
      elemental release, then brushed for 30 minutes at 90 strokes/min under 200 g of
      force with a soft toothbrush. The brushing was performed in neutral saline or
      lactic acid at pH 4 with or without toothpaste. The alloys were then transferred
      back into a biological medium for 1 week. Atomic absorption spectroscopy was used
      to measure the mass lost from each alloy during and in the week after brushing.
      Mass loss was expressed as micrograms per square centimeter of alloy surface, and
      the various brushing conditions were compared by analysis of variance and Tukey
      multiple comparison intervals (alpha = 0.05). RESULTS: During brushing, element
      release increased significantly over nonbrushed controls for all alloys except
      the Ni-Cr. Toothpastes, acidic solutions, or combinations of these conditions
      with toothbrushing further enhanced elemental release, but Ni release from the Ni
      Cr alloy increased the most (30-fold). In the week after brushing, brushing alone
      increased elemental release only from the Ni-Cr alloy. However, toothpastes and
      acidic solutions increased elemental release for all alloys significantly, except
      for the Au-Pd alloy. In general, elemental release during brushing was far
      greater than in the week after brushing. CONCLUSIONS: Under the conditions of
      this study, toothbrushing increased the elemental release from dental casting
      alloys.

PMID- 10895677
TI  - Vertical height loss: an investigation of four restorative materials opposing
      enamel.
AB  - PURPOSE: The objective of this in vitro investigation was to compare the vertical
      wear produced by cone-shaped styli of three ceramic restorative materials and a
      Type III gold alloy opposing flattened human enamel. Vertical wear was measured
      as enamel height loss, material stylus height loss, and total vertical height
      loss (the sum of the enamel height loss and the restorative material height
      loss). MATERIALS AND METHODS: Ten cone-shaped styli were fabricated from each of
      four restorative materials, which included two machined ceramics, a pressed
      ceramic, and a Type III gold alloy. To maintain the standardized shape, styli
      were not polished or glazed. Specimens were subjected to wear in the presence of
      water for 100,000 cycles at 1.2 Hz under a load of 75 N using a wear simulation
      device. Enamel wear was evaluated by profilometry, and stylus wear was evaluated
      by computer imaging. Vertical wear was reported as enamel height loss, material
      stylus height loss, and total vertical height loss (the sum of the enamel height
      loss and material height loss). Data were compared using one-way analysis of
      variance and Scheffe's analysis (alpha = 0.05). RESULTS: Significant differences
      existed among materials based on material height loss (p = .0001), enamel height
      loss (p = .0001), and total vertical height loss (p = .0118). No significant
      difference among the three ceramics was found in mean total height loss, which
      ranged from 0.280 to 0.305 mm. However, the Type III gold exhibited less mean
      total wear (0.231 +/- 0.082) than the pressed and one machineable ceramic. This
      machined ceramic exhibited the most material height loss (0.249 +/- 0.044 mm).
      With the other ceramics, mean enamel wear was significantly more (0.211 and 0.216
      mm, respectively). CONCLUSIONS: During wear simulation, pressed or machineable
      ceramics opposing flattened enamel exhibited a similar degree of total vertical
      height loss. One machined ceramic material wore significantly more than the other
      materials. The other machineable ceramic and the pressed ceramic wore the
      opposing enamel significantly more.

PMID- 10895678
TI  - Dental burs--what bur for which application? A survey of dental schools.
AB  - PURPOSE: The purpose of this study was to survey North American dental schools
      regarding recommendations for rotary instrumentation for fixed prosthodontic and
      operative procedures at the predoctoral and postgraduate level. MATERIALS AND
      METHODS: A 25-question survey was sent to 64 North American dental schools, of
      which 15 questions specifically related to rotary instrument recommendations. One
      questionnaire was addressed to the individual at each school having
      administrative responsibility for teaching tooth preparation techniques. A high
      response rate was assured by follow-up telephone calls and faxes. The
      distributions of bur recommendations for both predoctoral and advanced
      prosthodontic programs were analyzed by chi-squared tests at an a priori alpha =
      0.05. RESULTS: Completed surveys were received from 58 of 64 dental schools, a
      response rate > 90%. Medium grit burs predominate in predoctoral education for
      gross tooth reduction for fixed prosthodontics, whereas coarse grit burs
      predominate at the graduate level (p < .05). The use of the diamond bur alone
      predominates for axial wall refinement, whereas the use of carbide burs or
      carbide burs in combination with diamond burs prevails for marginal refinement (p
      < .05). In predoctoral operative dentistry, recommendations for cavity outline
      form were similar at all dental schools (p > .05) and were principally tungsten
      carbide (WC) burs. Carbide burs are the instrument of choice for internal walls,
      but the WC bur alone or in combination with diamond burs is preferred for
      refining composite margins (p < .05). CONCLUSIONS: There is a broad consensus
      within North American dental schools on rotary instrumentation used by dental
      students. There is a greater use of coarser grit burs for gross tooth reduction
      in fixed prosthodontics at the postgraduate than predoctoral level.

PMID- 10895679
TI  - Fabrication of a surgical stent for bilateral tuberosity and mandibular alveolar
      reduction.
AB  - A technique for constructing a single surgical stent to direct bilateral
      preprosthetic maxillary tuberosity reductions and mandibular alveolectomies is
      presented. The stent is fabricated using unaltered articulated definitive casts.
      The stent allows the oral surgeon to replicate the desired vertical dimension of
      occlusion for a thorough assessment of the sufficiency of the surgical revisions.
      The situation illustrated is unique, in that preoperatively, the patient's
      maxillary tuberosities were situated inferior and medial to their ipsilateral
      retromolar pads.

PMID- 10895680
TI  - Fabrication of complete denture bases reinforced with polyethylene woven fabric.
AB  - Incorporation of 5 layers of woven, high-modulus polyethylene fiber into acrylic
      resin denture bases produces substantial improvements in mechanical properties
      and dimensional changes. A modified split-pack technique has been developed using
      conventional dental-laboratory compression molding to accommodate multiple layers
      of woven fabric in complete denture bases. A recess formed in the resin by a
      spacer allows the reinforcement to be embedded in the denture base without
      exposing the fibers. Embedded fibers do not compromise the esthetics of complete
      dentures.

PMID- 10895681
TI  - A technique to create appropriate abutment tooth contours for removable partial
      dentures.
AB  - A technique is presented for using light-cured composite resin to create
      desirable contours on abutment teeth for the retention and support of removable
      partial dentures. The desired tooth shape is created on a diagnostic cast,
      captured in a clear temporary splint material, and formed in resin on the
      abutment teeth with the splint acting as a matrix.

PMID- 10895682
TI  - The history of articulators: a perspective on the early years, Part II.

PMID- 10895683
TI  - Staged approach for treatment of a severe ridge defect with implant placement. A
      case report.

PMID- 10895684
TI  - Protease enzyme profiles of 7 commercial enzymatic cleaners.

PMID- 10895685
TI  - Dentistry in 1000 A.D.

PMID- 10895686
TI  - Making non-competition clauses in employment agreements reasonable and
      enforceable.

PMID- 10895687
TI  - Apoptosis in Porphyromonas gingivalis-specific T-cell lines.
AB  - Fluorescence-activated cell sorter analysis and transmission electron microscopy
      were used to determine the presence of apoptotic cells in Porphyromonas
      gingivalis-specific T-cell lines established from the peripheral blood of 10 P.
      gingivalis-infected individuals. P. gingivalis outer membrane antigens were
      presented to the T cells by autologous Epstein-Barr virus-transformed B cells for
      6, 24, 48 and 72 h. Transmission electron microscopy demonstrated the presence of
      typical apoptotic cells in all cultures. Annexin V-positive cells were present at
      low concentrations at all 4 four periods. A mean of approximately 2-3% of the CD4
      cells and 1-3.5% of the CD8 cells were annexin V-positive, with an increase to
      around 5.5% positive CD4 cells at 6 h in wells containing P. gingivalis compared
      with cultures not containing antigen. This difference was not, however,
      significant at the 0.05 level (P = 0.073). The mean (+/- standard error) CD4:CD8
      ratios of the T-cell lines when first established using peripheral blood
      mononuclear cells as antigen-presenting cells was significantly higher (5.2 +/-
      1.1) than when transformed B cells were used as antigen-presenting cell (1.2 +/-
      0.5). While this study has shown apoptosis occurring in the T-cell lines, it has
      not shown definitively that the reversion in the CD4:CD8 ratio in the P.
      gingivalis-specific T cells following antigen presentation by autologous Epstein
      Barr virus-transformed B cells is due to apoptosis of a CD4 population.
      Alternatively, the reversion in the CD4:CD8 ratio could be due to a selective
      proliferation of the CD8 population which, in turn, could be relevant to the
      immunopathology of periodontal disease induced by P. gingivalis.

PMID- 10895688
TI  - Isolation and characterization of the rml gene homologs from Porphyromonas
      gingivalis.
AB  - We cloned four genes from the Porphyromonas gingivalis chromosome, the gene
      products of which catalyze the anabolism of dTDP-L-rhamnose from D-glucose-1
      phosphate when they were expressed in Escherichia coli. The amino acid sequences
      deduced from these genes showed significant homology to proteins encoded by the
      rml genes involved in dTDP-L-rhamnose biosynthesis in other gram-negative
      bacteria. Reverse transcriptase polymerase chain reaction analysis revealed that
      these four genes are expressed as a single transcript in P. gingivalis. To
      clarify the role of the rml gene homologs in this organism, construction of
      mutants defective in the rml gene homologs was attempted by allelic exchange.
      Unexpectedly, any mutants defective in the rml gene homologs were unable to be
      isolated, and the allelic exchange was possible only if the wild-type rml gene
      homologs were present on the chromosome. These results suggest that the rml gene
      homologs might be essential for the viability of P. gingivalis under the culture
      conditions used in this study.

PMID- 10895689
TI  - Proteolysis and utilization of albumin by enrichment cultures of subgingival
      microbiota.
AB  - Subgingival dental plaque consists mainly of microorganisms that derive their
      energy from amino acid fermentation. Their nutrient requirements are met by the
      subgingival proteolytic system, which includes proteases from microorganism and
      inflammatory cells, and substrate proteins from sulcus exudate, including
      albumin. To determine the selective effect of individual proteins on microbiota,
      we used albumin as the main substrate for growth. Eight subgingval plaque samples
      from untreated periodontal pockets of patients with adult periodontitis were
      inoculated in peptone yeast medium with bovine albumin (9 g/l). After three
      subculture steps, cell yields of the enrichment cultures at the medium with 0,
      1.25, 2.5, 5, 10, and 20 g/l albumin were determined. Proteolytic activity
      (U/absorbance at 550 nm) of the enrichment cultures and different isolates
      derived from the cultures was estimated by the degradation of resorufin-labeled
      casein. It was observed that the yield of the mixed culture was albumin limited,
      and the proteolytic activities of the cultures in albumin broth were higher than
      in control (peptone broth). Among the isolates from the enrichment cultures,
      Peptostreptococcus micros, Prevotella melaninogenica, Prevotella buccae and
      Prevotella bivia demonstrated proteolysis. The frequent occurrence of
      Streptococcus gordonii and Streptococcus anginosus in the albumin cultures is
      explained by their ability to utilize arginine as an energy source for growth.
      Albumin in the medium was partly degraded by pure cultures but completely
      consumed in enrichment cultures, indicating synergy of bacterial proteinases. It
      is concluded that the subgingival microbiota possesses proteolytic activity and
      may use albumin as a substrate for their growth. Enrichment cultures on albumin
      may serve as a relatively simple in vitro model to evaluate the effects of
      proteinase inhibitors.

PMID- 10895690
TI  - Prevalence of beta-lactamase-producing strains among 149 anaerobic gram-negative
      rods isolated from periodontal pockets.
AB  - In a prospective study, 47 adults presenting a rapidly progressive periodontitis
      were selected in order to evaluate the prevalence of beta-lactamase-producing
      strains among oral anaerobic gram-negative rods. Predominant anaerobes were
      identified from two of the deepest periodontal pockets. beta-Lactamase-positive
      strains fulfilled to at least two of three criteria: positive nitrocefin test,
      penicillin Etest minimal inhibitory concentration > 1 microgram/ml, and disk
      diffusion synergy between amoxycillin and clavulanic acid > 10 mm. At least one
      beta-lactamase-producing strain was found in 53.2% of patients and 39.4% of the
      periodontal pockets investigated. Prominent beta-lactamase-positive species were
      Prevotella buccae and Prevotella intermedia (respectively 16 of 38: 42% and 18 of
      52: 35% positive strains), followed by Prevotella bivia, Prevotella disiens,
      Prevotella denticola and Fusobacterium nucleatum (respectively 1 of 6: 17%, 1 of
      10: 10%, 1 of 10: 10%, and 1 of 13: 8% positive strains). No beta-lactamase
      producer could be evidenced in Porphyromonas gingivalis (10 strains tested). All
      the beta-lactamase-positive strains with the nitrocefin test had penicillin
      minimal inhibitory concentrations > 1 microgram/ml with the Etest, and a strong
      synergy between amoxicillin and clavulanic acid was always observed.

PMID- 10895691
TI  - Adhesion of oral Candida species to human buccal epithelial cells following brief
      exposure to nystatin.
AB  - Opportunistic oral infections caused by Candida albicans and non-albicans Candida
      species are particularly common in compromised patients. Nystatin, which belongs
      to the polyene group of antimycotics, is frequently used as a topical agent in
      the treatment of oro-pharyngeal candidosis. It is recognized that due to the
      delivery mode of nystatin (i.e. topical, intermittent), as well as the cleansing
      effect of saliva within the oral environment, the yeasts undergo a relatively
      brief exposure to this drug during treatment. Nevertheless, there is a sparsity
      of data on the effect of such brief exposure to nystatin on the pathogenic
      attributes of Candida such as their adherence to host surfaces. The adhesion of
      microbes to host mucosal surfaces is a major determinant of successful
      colonization and infection. Thus the main aim of our investigation was to compare
      the in vitro adhesion of 30 oral isolates of Candida belonging to six different
      species (comprising Candida albicans, Candida tropicalis, Candida glabrata,
      Candida guilliermondii, Candida krusei and Candida parapsilosis) to human buccal
      epithelial cells, following their brief exposure (1 h) to minimum inhibitory
      concentration of nystatin, and subsequent removal of the drug. The adhesion of
      these isolates to buccal epithelial cells was assessed by a previously described
      adhesion assay. Compared with the controls, there was a significant reduction in
      buccal epithelial cell adhesion of all six Candida species after drug exposure
      (54%-68%). However the adhesion of C. albicans isolates was the least affected by
      nystatin exposure, which was significantly different from that of the non
      albicans species. These findings imply that sub-therapeutic levels of nystatin,
      which are likely to persist in the oral cavity during dosing intervals, may also
      be beneficial, as they inhibit candidal colonization. The significant difference
      in nystatin-induced suppression of adhesion between C. albicans and the non
      albicans species investigated is a further testimonial for the pre-eminent
      virulence of the former species.

PMID- 10895692
TI  - Candida albicans triggers interleukin-6 and interleukin-8 responses by oral
      fibroblasts in vitro.
AB  - Oral candidiasis is the most frequent opportunistic infection associated with an
      immunocompromised host. Production of proinflammatory cytokines, such as
      interleukin-6 (IL-6) and IL-8, by host cells in response to Candida albicans can
      be expected to have a major impact in the activation of immune effector cells
      against the invading microorganism. Using a human cell--C. albicans coculture
      model system, we determined that this microorganism can trigger secretion of
      these potent chemoattractant and proinflammatory cytokines by oral mucosal
      fibroblasts. This response varied depending on the infecting strain and required
      fungal viability, germination of yeast into hyphae and mannose-mediated direct
      contact between the host cell and Candida. The secretion of proinflammatory
      cytokines by oral mucosal fibroblasts in response to C. albicans suggests that
      these cells have the potential to enhance the host defense against this organism
      in vivo. This may have important implications in controlling fungal overgrowth in
      the oral cavity.

PMID- 10895693
TI  - Expression of beta-defensin genes by human salivary glands.
AB  - This study investigated expression of genes encoding human beta-defensins 1 and 2
      by human salivary glands. Tissues from surgical biopsies were collected fresh
      onto ice and stored in liquid nitrogen. Total RNA was extracted using Trizol
      reagent and human beta-defensin messenger RNA detected by reverse transcriptase
      polymerase chain reaction amplification. DNA sequencing of amplified fragments,
      after ligation into pGEM-T Easy vector and transformation of competent
      Escherichia coli, confirmed identities of cloned fragments. Human beta-defensin 1
      messenger RNA was detected in all 25 samples that generated amplifiable cDNA, as
      assessed using abl-specific primers. Three of 13 submandibular gland samples (two
      normal, one chronically inflamed), and 2 of 2 minor salivary gland samples (one
      normal, one chronically inflamed) expressed human beta-defensin 2 messenger RNA.
      All six parotid gland samples studied were negative for human beta-defensin 2
      messenger RNA. Thus, human beta-defensin 1 gene expression occurred in all human
      major and minor salivary glands studied, whereas human beta-defensin 2 expression
      occurred only in a small number of gland samples.

PMID- 10895694
TI  - Antibodies to Treponema pallidum in serum from subjects with periodontitis:
      relationship to pathogen-related oral spirochetes.
AB  - Pathogen-related oral spirochetes were identified in dental plaque using
      monoclonal antibodies to putative Treponema pallidum-specific proteins, and serum
      from subjects with necrotizing ulcerative gingivitis contained immunoglobulin G
      to molecules thought to be restricted to T. pallidum. The purpose of this study
      was to determine whether subjects with periodontitis were more likely to have
      serum antibodies to T. pallidum if pathogen-related oral spirochetes were
      present. Pathogen-related oral spirochetes were detected in subgingival plaque
      from 27 of 40 subjects, and 33 subjects had serum antibodies that bound T.
      pallidum proteins in immunoblots. Subjects with pathogen-related oral spirochetes
      were no more likely to have IgA, IgG or IgM to 15-, 37- or 47-kDa proteins than
      were subjects without pathogen-related oral spirochetes. In contrast to subjects
      with necrotizing ulcerative gingivitis, subjects with periodontitis had no
      detectable antibodies to 37- or 12-kDa proteins. Further research is needed to
      identify the stimulus for antibodies that cross-react with T. pallidum proteins.

PMID- 10895695
TI  - Adherence to and penetration through endothelial cells by oral treponemes.
AB  - Oral spirochetes were co-incubated with monolayers of endothelial cells seeded
      into multiwell plates or onto filters mounted in plastic chambers. Attachment was
      assessed using an enzyme-linked immunosorbent assay and scanning electron
      microscopy. Invasiveness was determined by monitoring media beneath filters
      within chambers for spirochetes using darkfield microscopy. Transmission electron
      microscopy was used to estimate intercellular and intracellular passage of
      spirochetes through monolayers. All tested treponemes attached to monolayers in a
      dose- and time-dependent manner, except Treponema phagedenis. A few treponemes
      were observed within host cell cytoplasm. Unidentified spirochetes obtained from
      dental plaque were also invasive. Results indicate that oral spirochetes possess
      virulence-associated characteristics shared with pathogenic spirochetes. Further
      studies should examine the possibility that invasive spirochetes could
      disseminate from within affected gingiva.

PMID- 10895696
TI  - Factors affecting the formation of spherical bodies in the spirochete Treponema
      denticola.
AB  - The oral spirochete Treponema denticola typically is a helically shaped, motile
      bacterial cell. However, morphological variations of T. denticola cells in the
      form of "spherical bodies" are sometimes seen. Little is known about the
      environmental factors that cause their formation. The effects of oxygen, growth
      temperature, nutrient depletion and the addition of metabolic end-products were
      tested to determine their role in the morphogenesis of the spherical bodies. It
      was found that the age of the culture, the omission of individual components
      (yeast extract, rabbit serum, volatile fatty acids or thiamine pyrophosphate)
      from the medium and the addition of the metabolic end product lactic acid
      enhanced the formation of these bodies. However, their formation was decreased
      upon omission of the medium components asparagine and sodium bicarbonate.

PMID- 10895697
TI  - Genotyping of Actinobacillus actinomycetemcomitans serotype d isolates based on
      polymerase chain reaction.
AB  - The aims of the study were to determine the genetic diversity of the rare
      Actinobacillus actinomycetemcomitans serotype d and to compare the ability of the
      repetitive extragenic palindromic element (REP)-based polymerase chain reaction
      (PCR) with that of the arbitrarily primed (AP)-PCR to discriminate between and
      within A. actinomycetemcomitans serotypes. The material included 26 A.
      actinomycetemcomitans serotype d isolates, 3 reference strains, and 21 A.
      actinomycetemcomitans isolates, representing the previously described 17 AP-PCR
      genotypes from 4 serotypes (a, b, c and e). Among A. actinomycetemcomitans
      serotype d isolates (n = 26), the AP-PCR primer distinguished 2 genotypes,
      whereas the REP-primer pair (REP1R-I and REP2-I) and the (GACA)4 primer each
      produced one genotype. Among the total of 50 A. actinomycetemcomitans isolates,
      REP-primer pair distinguished 6 genotypes, the primer (GACA)4 7 genotypes, and
      the AP-PCR 19 genotypes. Among A. actinomycetemcomitans serotype a isolates (n =
      6), REP-primer pair yielded 3 genotypes and (GACA)4 and AP-PCR primer 4
      genotypes, and among serotype e isolates (n = 6) 3 genotypes. All serotype b
      isolates (n = 7), representing the AP-PCR genotypes 2, 9, 8, 12, 13, 16 and
      serotype c isolates (n = 5), AP-PCR genotypes 3, 4, 14, 15, belonged to the
      (REP1R-I and REP2-I)-PCR genotype 4 and to the (GACA)4-PCR genotype 4. In
      conclusion, based on both the AP-PCR method and the less discriminative REP-PCR
      methods, the present genotyping results indicated limited genetic diversity among
      serotype d isolates of A. actinomycetemcomitans.

PMID- 10895698
TI  - Antimicrobial effect of acidified nitrite on cariogenic bacteria.
AB  - The antimicrobial agent nitric oxide (NO) is formed in the mouth and its
      concentration is directly related to salivary nitrite, which in turn is related
      to dietary nitrate intake. The aim of this study was to determine whether nitrite
      under acidic conditions will have an inhibitory effect, possibly occurring
      through NO production, on Streptococcus mutans, Lactobacillus casei and
      Actinomyces naeslundii. Whereas the growth of S. mutans was inhibited by a more
      acid pH, the addition of nitrite caused a marked, further dose-dependent
      reduction in bacterial numbers after 24 h of exposure. Similar effects were
      observed with A. naeslundii and L. casei. The ability of these bacteria to
      recover from nitrite exposure was also markedly affected by nitrite
      concentration. At acidity levels below pH 7, low concentrations of nitrite (0.2
      mM) caused effective complete killing of S. mutans, with similar effects on the
      other organisms tested. These results demonstrate the possibility that nitrite in
      saliva has an effect on the growth and survival of cariogenic bacteria.

PMID- 10895699
TI  - Case study. Aneurysmal bone cyst.

PMID- 10895700
TI  - California's sweet taste of freedom.

PMID- 10895701
TI  - Upstairs in the corporate world.

PMID- 10895702
TI  - Is alcohol that dangerous in dentistry?

PMID- 10895703
TI  - A committee's morals.

PMID- 10895704
TI  - More than just 'skin deep'.

PMID- 10895705
TI  - Case study. Dentin dysplasia.

PMID- 10895706
TI  - An Alaskan adventure.

PMID- 10895707
TI  - Fraud or confusion?

PMID- 10895708
TI  - Keeping the sharper edge.

PMID- 10895709
TI  - Case study. Hand, foot, and mouth disease.

PMID- 10895710
TI  - The interview.

PMID- 10895711
TI  - How they "manage" behind prison walls.

PMID- 10895713
TI  - Case study. Primordial cyst/OKC.

PMID- 10895712
TI  - St. John's Wort: is it effective and harmless?

PMID- 10895714
TI  - An earful.

PMID- 10895715
TI  - Optimal answers.

PMID- 10895716
TI  - Blending into Romania.

PMID- 10895717
TI  - Case study. Periapical cemento-osseous dysplasia.

PMID- 10895718
TI  - Preceptorship + managed care = unemployment line?

PMID- 10895719
TI  - Lighten up!

PMID- 10895720
TI  - Painful inspiration.

PMID- 10895721
TI  - Case study. Polymorphous low-grade adenocarcinoma.

PMID- 10895722
TI  - A spirit of collaboration ... and, yes, independence.

PMID- 10895723
TI  - A summer in Mongolia.

PMID- 10895724
TI  - Fluoride supplements.

PMID- 10895725
TI  - To stain ... or not to stain.

PMID- 10895726
TI  - Case study. Basal cell carcinoma.

PMID- 10895727
TI  - Going the 'full monty' in dental hygiene.

PMID- 10895728
TI  - Soft tissue therapy with lasers.

PMID- 10895729
TI  - Sporting injuries.

PMID- 10895730
TI  - Take my (bad) breath away ... please?

PMID- 10895731
TI  - Ongoing infection-control training.

PMID- 10895732
TI  - Are herbal remedies a natural solution?

PMID- 10895733
TI  - Patient satisfaction with dental care in a municipal hospital.
AB  - Quality assurance activities are an important part of a hospital dental
      department. This study reports the results of a patient satisfaction
      questionnaire distributed as part of the quality assurance activities at a
      municipal hospital. The results show patient satisfaction questionnaires are
      applicable to the hospital setting, patients report relative satisfaction with
      the care received, and they can identify specific areas of satisfaction and
      dissatisfaction. The number of visits, easy access and convenience to the clinic,
      and out-of-pocket payment for dental care are predictive of satisfaction with the
      dental care received at this clinic.

PMID- 10895734
TI  - Patient age and general dentists' treatment decisions.
AB  - To test whether a patient's age plays a role in dentists' treatment planning
      decisions, a convenience sample of 159 general dentists attending a state dental
      society annual meeting was presented a vignette including intra-oral photographs,
      a brief case history and clinical diagnosis of a patient. The patient was
      partially dentate, and was described as having irreversible pulpitis of tooth
      #19. Three versions of the vignette were developed, with identical materials and
      information except for the patient's age (either 44, 65, or 84 years), and were
      randomly assigned to the participating dentists who were asked to develop a
      treatment plan for the patient's mandibular arch. The dentists planned limited
      therapy for the 84 year old because of their assumptions about the patient's
      brief life expectancy, cost, concern about the inability of the patient to
      tolerate extensive treatment, and a low cost/benefit ratio. These findings
      suggest that a patient's age influences general dentists' treatment planning
      decisions, perhaps limiting the treatment options offered to older adults.
      Additional research is necessary to further test these associations.

PMID- 10895735
TI  - A clinical comparative trial of saliva substitutes in radiation-induced salivary
      gland hypofunction.
AB  - Use of saliva substitutes may become necessary to manage xerostomia when no means
      of stimulating saliva production is effective. Few clinical trials have compared
      products that may act as salivary substitutes. Patients' preference of products
      depended on effect duration, lubrication, taste, delivery system, and cost. Many
      patients did not continue with the use of the products studied, and instead chose
      to rely on frequent use of water. Clinical trials of the products are recommended
      before prescription to indicate what may be the best choice for the individual
      patients.

PMID- 10895736
TI  - A comparison between fluconazole tablets and clotrimazole troches for the
      treatment of thrush in HIV infection.
AB  - Fluconazole, a newly available triazole, has been evaluated extensively as a
      treatment for thrush. It has been effective in the treatment of this condition in
      patients with HIV infection. Clotrimazole troches have been a common treatment
      for thrush in patients with HIV infection for several years. This study compared
      the efficacy and safety of fluconazole 100 mg tablets once per day versus
      clotrimazole 10 mg troches five times per day in the treatment of thrush in
      patients with HIV infection. Patients were evaluated at baseline, day 7, 14, 28,
      and 42. The following parameters were evaluated: clinical cure, colonization at
      the end of treatment, relapse at day 28, and relapse at day 42. Side effects
      including liver enzyme values were also monitored. Clinical cure was superior
      with fluconazole tablets than with clotrimazole troches. Also, rates of
      colonization at the end of therapy and relapse at days 28 and 42 were less with
      fluconazole tablets than with clotrimazole troches. However, these differences
      were not statistically significant. Patient compliance with fluconazole was
      superior to that of clotrimazole. This difference was statistically significant.
      Both fluconazole tablets and clotrimazole troches are effective in treating
      thrush in patients with HIV infection. The avoidance of multiple-per-day dosing
      would appear to favor fluconazole.

PMID- 10895737
TI  - Self-inflicted oral trauma: report of case.
AB  - An easily made, reusable mouth-guard suitable for comatose patients with
      neuropathologic chewing is presented. Its use is described for a comatose child
      with self-inflicted tongue trauma.

PMID- 10895738
TI  - Social work in a dental program for the developmentally disabled.
AB  - This article discusses the role of a social worker in a dental school based
      program for the developmentally disabled. Developmentally disabled people
      constitute a heterogeneous population with problems that often prevent them from
      receiving appropriate dental services. A social worker in the dental care setting
      can help this population access dental services. Data gathered during a 2-year
      period support the hypothesis that patients living at home present more obstacles
      to dental care and require more social work intervention in obtaining dental care
      than patients living in residential settings.

PMID- 10895739
TI  - Self-assessment of dental health among Danish noninstitutionalized psychiatric
      patients.
AB  - This survey provides a description of the living conditions, dental health self
      assessment, dental health behavior, and knowledge and attitudes to dental care in
      a population of noninstitutionalized psychiatric patients. A total of 84
      individuals (70% of the persons selected) were interviewed using a pretested
      structured questionnaire. One of five participants did not perform oral hygiene
      as a daily routine and 45% had no regular dental visit habits. A proportion of
      about 40% reported symptoms from teeth or gingiva within the previous year.
      Despite an acceptable level of general knowledge on caries and periodontal
      problems, only a small proportion were aware of the caries-inducing potential of
      psychotropic drugs. People with more than five admissions to the psychiatric ward
      more often reported symptoms from teeth and gingiva; irregular dental visit
      habits were also related to number of admissions and to manic-depression. The
      survey indicates poor oral health among psychiatric patients compared with the
      general population and the need for specific oral care programs leveled at
      noninstitutionalized psychiatric patients is stressed.

PMID- 10895740
TI  - Spinal cord injury and direct laryngoscopy--the legend lives on.

PMID- 10895741
TI  - The effects of regional analgesia on the progress of labour and delivery.

PMID- 10895742
TI  - Sedation of children by non-anaesthetists.

PMID- 10895744
TI  - Epidural ropivacaine with fentanyl following major gynaecological surgery: the
      effect of volume and concentration on pain relief and motor impairment.
AB  - In a prospective, randomized, double-blind study, 40 patients undergoing
      gynaecological oncology surgery received either 0.1% ropivacaine with fentanyl 1
      microgram ml-1 or 0.2% ropivacaine with fentanyl 2 micrograms ml-1. A PCEA pump
      was set to deliver ropivacaine 8 mg with fentanyl 8 micrograms with each
      successful demand and a lockout period of 15 min without background infusion.
      Patients were observed for rest and activity pain VAS, side effect incidence,
      peak expiratory flow rate (PEFR), leg strength, sensory block to cold and
      pinprick, and PCEA usage into the second postoperative day. Passive and active
      pain scores for both groups were both satisfactory and comparable for the
      duration of the study. There were no differences between groups with regard to
      side effects. There was a 24% increase in total drug used in the high
      concentration/low-volume group (P < 0.05). The study demonstrated that PCEA
      ropivacaine with fentanyl is an effective means of postoperative analgesia for
      this patient population. Reduced drug consumption with high-volume/low
      concentration solution confirms similar findings by other investigators using
      alternate local anaesthetic agents, and suggests that the therapeutic ratio of
      ropivacaine is widened if a low-concentration/high-volume solution is used.

PMID- 10895743
TI  - Randomized controlled comparison of epidural bupivacaine versus pethidine for
      analgesia in labour.
AB  - We compared the incidence of Caesarean delivery in nulliparous women randomized
      to receive epidural analgesia with those randomized to intramuscular (i.m.)
      pethidine. On admission to the delivery suite in established labour, 802
      nulliparae had already agreed to be randomized with respect to their first
      analgesia. One hundred and eighty-eight women required either no analgesia or 50%
      nitrous oxide in oxygen (Entonox) only. Of the remaining 614 women, 310 were
      randomly allocated to receive i.m. pethidine up to 300 mg and 304 to receive
      epidural bupivacaine. Labour management was standardized according to the
      criteria for active management of labour. The intention-to-treat analysis showed
      similar Caesarean section rates in those randomized to epidural (12%) or
      pethidine analgesia (13%). The difference in Caesarean rate was -1.1% with 95%
      confidence intervals from -6.3% to +4.1%. The normal vaginal delivery rates were
      similar (epidural, 59%; pethidine, 61%).

PMID- 10895745
TI  - Caesarean section for placenta praevia: a retrospective study of anaesthetic
      management.
AB  - A retrospective survey of anaesthesia for Caesarean section (CS) for placenta
      praevia was performed, covering the period between January 1, 1984 and December
      31, 1998. Three hundred and fifty consecutive cases of placenta praevia were
      identified. Overall a regional technique was used 60% of the time. Five women had
      a placenta accreta which required Caesarean hysterectomy: one had general
      anaesthesia (GA) throughout and four initially received a single-shot spinal
      injection. Of these latter four cases, two were converted to GA during the
      hysterectomy and two continued with spinal anaesthesia throughout. Two other
      women (both GA), suffered postoperative thrombotic episodes (one pulmonary
      embolus and one cerebral thrombosis) but made full recoveries. Control of blood
      pressure when using regional anaesthesia (RA), even in the presence of
      considerable haemorrhage, was not a problem. Statistical regression models
      indicated that RA was associated with a significantly reduced estimated blood
      loss and reduced need for blood transfusion. This retrospective survey finds no
      data to support the much quoted aphorism that RA is contraindicated for CS in the
      presence of placenta praevia.

PMID- 10895746
TI  - Does wound irrigation with triamcinolone reduce pain after surgery to the lumbar
      spine?
AB  - This prospective, randomized study compared postoperative pain scores, morphine
      consumption and length of stay in 95 adults who underwent elective lumbar spine
      surgery via a posterior incision. Immediately prior to closure the wound was
      irrigated with triamcinolone 40, 20 or 0 mg. Visual analogue scale pain scores at
      24 h after surgery were median 12 (interquartile range 3-24), 15 (6-34) and 33
      (20-59) mm for patients receiving triamcinolone 40, 20 mg or no steroid,
      respectively (P < 0.0005, Kruskal-Wallis test). Total morphine usage after 24 h
      was 26 (21-39), 27 (17-43) and 43 (27-73) mg for the same groups (P < 0.001,
      Kruskal-Wallis test). The proportion of patients discharged from hospital on the
      first day after surgery was 83.9, 77.4 and 54.8% for patients receiving
      triamcinolone 40, 20 mg and no steroid, respectively (P < 0.028, chi-squared
      test). Extra-dural triamcinolone reduces pain after lumbar spine surgery and
      reduces time to discharge from hospital.

PMID- 10895747
TI  - Breath interval as a measure of dynamic opioid effect.
AB  - We measured breath interval to characterize the time course of opioid effect in
      anaesthetized patients breathing spontaneously during knee replacement surgery
      with concurrent regional nerve blockade. Breath interval was recorded before and
      after a single dose of fentanyl 0.75 microgram kg-1 i.v. Breath interval was
      measured between the start of successive inspirations, identified by a decrease
      in carbon dioxide concentration, sampled at the laryngeal mask connection.
      Nineteen patients were admitted to the study, of whom nine were withdrawn (there
      was a recording failure for one patient, five patients had inadequate block and
      three were excessively depressed by the fentanyl). Using MKMODEL software, the
      mean (SD) dynamic elimination half-life and dynamic mean brain residence time of
      fentanyl were 15.3 (7.8) and 24.1 (8.1) min, respectively. The times to detection
      of change from baseline, and peak effect of fentanyl on breath interval were 0.9
      (0.6) and 5.2 (1.4) min, respectively. Breath interval increased from 2.9 (1.0) s
      to a maximum of 9.0 (5.7) s. There were no differences between the time course of
      changes in breath interval and end-tidal carbon dioxide concentrations. End-tidal
      carbon dioxide concentrations increased from a baseline of 6.6 (0.9)% to a peak
      of 8.2 (0.8)%. Breath interval was a useful and reproducible method of monitoring
      the duration of opioid effect in anaesthetized patients breathing spontaneously
      when surgical stimulation was not affecting the CNS. The data provide information
      on the duration of action of fentanyl and could guide dosage.

PMID- 10895748
TI  - Comparison of ketamine and morphine for analgesia after tonsillectomy in
      children.
AB  - In a double blind study we compared the effects of i.m. ketamine with morphine on
      postoperative analgesia in children undergoing tonsillectomy. Eighty children
      (aged 6-15 yr) were randomized to receive either i.m. morphine 0.1-0.15 mg kg-1
      or ketamine 0.5-0.6 mg kg-1, after induction of a standard general anaesthetic.
      Pain scores 30 min after extubation were higher (P < 0.05) in the ketamine group,
      but were similar thereafter to the morphine group. Mean (SD) times to recovery
      from anaesthesia were 20.1 (SD 6.5) min in the ketamine group compared to 14.2
      (5.6) min in the morphine group (P < 0.01). There were no differences in
      supplemental analgesia requirements, or the incidence of vomiting or dreaming
      between the groups. We conclude that ketamine 0.5 mg kg-1 i.m. may be an
      alternative analgesic for children undergoing tonsillectomy.

PMID- 10895749
TI  - Sedation and general anaesthesia in children undergoing MRI and CT: adverse
      events and outcomes.
AB  - Quality assurance data were collected prospectively for children who were sedated
      (n = 922) or given general anaesthesia (n = 140) for magnetic resonance imaging
      (MRI) or computerized tomography (CT). The data included patient characteristics,
      concurrent medication, adequacy of sedation, adverse events and requirement for
      escalated care. The quality of scans was evaluated. Reasons for preselection of
      general anaesthesia included previously failed sedation (28%), potential for
      failed sedation (32%) and perceived medical risk (14%). Hypoxaemia occurred in
      2.9% of sedated children, and was more common in children classified as ASA III
      or IV. Sedation was inadequate for 16% of children and failed in 7%. Failed
      sedation was associated with greater age (P = 0.009), higher ASA status (P =
      0.04) and use of benzodiazepines as sole sedatives (P < 0.03). More of the
      children who underwent general anaesthesia were ASA III or IV than sedated
      children, yet the procedure was successful in all the children who underwent
      general anaesthesia, with one incident of laryngospasm. Excessive motion was
      noted in 12% of scans of sedated children and 0.7% of those completed with
      general anaesthesia. We conclude that sedation of children for MRI and CT is
      associated with risks of hypoxaemia and of inadequate or failed sedation. These
      adverse events were more likely to occur in older children, those with a higher
      ASA status and those in whom benzodiazepines had been used as sole sedatives. For
      a preselected high-risk group of children, general anaesthesia may make MRI and
      CT scans more successful with minimal adverse events.

PMID- 10895750
TI  - Fentanyl and midazolam anaesthesia for coronary bypass surgery: a clinical study
      of bispectral electroencephalogram analysis, drug concentrations and recall.
AB  - Bispectral index (BIS) was assessed as a monitor of depth of anaesthesia during
      fentanyl and midazolam anaesthesia for coronary bypass surgery. In 10 patients
      given morphine premedication, anaesthesia was induced with a combination of
      midazolam and fentanyl and thereafter maintained with a continuous infusion of a
      mixture of midazolam and fentanyl 5 and 50 micrograms kg-1 h-1, respectively. BIS
      was recorded continuously but not shown to the attending anaesthetist. Plasma
      concentrations of midazolam and fentanyl were measured five times during the
      procedure. An auditory stimulus was given during bypass. All patients were
      interviewed twice after operation for explicit and implicit recall. No patient
      had any anaesthetic complications. BIS decreased during anaesthesia, but varied
      considerably during surgery (range 36-91) with eight patients having values > 60.
      Midazolam and fentanyl drug concentrations did not correlate with BIS. No patient
      reported explicit or implicit recall. During clinically adequate anaesthesia with
      midazolam and fentanyl BIS varies considerably. The most likely reason is that
      BIS is not an accurate measure of the depth of anaesthesia when using this
      combination of agents.

PMID- 10895751
TI  - Haemodynamic effects of the lateral decubitus position and the kidney rest
      lateral decubitus position during anaesthesia.
AB  - We measured the haemodynamic effects of changing from the supine position to the
      lateral decubitus (lateral) position, and then to the kidney rest lateral
      decubitus (kidney) position in 12 patients undergoing nephrectomy under
      isoflurane anaesthesia. Eight control patients undergoing pulmonary surgery
      remained in the lateral position. The lateral position produced no significant
      changes. In the kidney position, however, significant reductions occurred in the
      mean arterial (P < 0.01), right atrial (P < 0.05) and pulmonary artery wedge
      pressures (P < 0.01). There were also significant reductions in cardiac index
      (from 3.04 (SD 0.21) to 2.44 (0.26) litre min-1 m-2, P < 0.01) and stroke volume
      index (from 40 (5) to 31 (5) ml beat-1 m-2, P < 0.01). The systemic vascular
      resistance index increased significantly (P < 0.05). Cardiac output was probably
      reduced by a decrease in venous return and an increase in systemic vascular
      resistance.

PMID- 10895752
TI  - Do fluid administration and reduction in norepinephrine dose improve global and
      splanchnic haemodynamics?
AB  - We studied global and splanchnic haemodynamics in patients with septic shock,
      while reducing norepinephrine doses by progressive fluid loading administration.
      Ten patients (six female, four male, aged 39-86 yr, mean 61 yr) were assessed
      using a transpulmonary thermo-dye dilution technique to measure cardiac output,
      intrathoracic blood volume and total blood volume. Splanchnic blood flow was
      measured by the steady state indocyanine green technique using a hepatic venous
      catheter. Gastric mucosal blood flow was estimated by regional carbon dioxide
      tension (PRCO2). Hydroxyethylstarch was infused in two stages while maintaining
      mean arterial pressure, allowing a reduction in norepinephrine dose from 0.54 to
      0.33 to 0.21 microgram kg-1 min-1. Mean (SD) heart rate significantly decreased,
      from 104 (13) to 94 (15) beats min-1. Total blood volume index (mean (SD))
      increased from 2650 (638) to 3655 (885) ml m-2, intrathoracic blood volume index
      from 888 (204) to 1050 (248) ml m-2 and cardiac index from 3.6 (1.0) to 4.0 (0.9)
      litres min-1 m-2. Splanchnic blood flow did not change significantly--either
      absolute (from 0.81 to 0.98 litres min-1 m-2) or fractional (from 22.3% to
      23.9%). Gastric mucosal (PRCO2) increased from 7.5 (2.5) to 9.0 (2.8) kPa. The
      PCO2 gap, i.e. the difference between regional and end-tidal PCO2, increased from
      3.1 (2.5) to 4.0 (2.9) kPa. Marked individual variation in responses suggests
      that norepinephrine dose reduction by fluid loading in patients with stabilized
      septic shock does not necessarily increase global or splanchnic blood flow.

PMID- 10895753
TI  - Serum myoglobin and creatine kinase following surgery.
AB  - Serum myoglobin (by radioimmunoassay) and creatine kinase were measured for up to
      7 days in 30 patients following surgical procedures, including total hip
      replacement and bilateral subcostal abdominal incisions. Serum myoglobin reached
      a maximum of 1390 micrograms litre-1 (median 345 micrograms litre-1 for major
      surgery patients) on the first postoperative day but levels were still elevated
      by day 7 in some patients. Creatine kinase reached a maximum of 1339 i.u. litre-1
      at day 2 (median 422 i.u. litre-1 for major surgery patients), generally peaking
      1 day after myoglobin in individual patients. These values may have significance
      when investigating a suspicion of coincident perioperative events such as
      myocardial infarction or malignant hyperthermia.

PMID- 10895754
TI  - Ignorance of post-exposure prophylaxis guidelines following HIV needlestick
      injury may increase the risk of seroconversion.
AB  - Needlestick injury is relatively common amongst healthcare workers, particularly
      those, such as anaesthetists, who regularly perform invasive procedures. The risk
      of seroconversion following needlestick injury may be reduced by knowledge of
      body fluids that are high risk and knowledge of post-exposure prophylaxis
      following possible HIV-contaminated needlestick injury. A structured
      questionnaire was used to establish knowledge regarding high HIV risk body fluids
      and measures to be taken following needlestick injury in anaesthetists working in
      a large teaching hospital. Completed questionnaires were obtained from all 76
      anaesthetists working in the department (39 consultant, 37 trainee/non
      consultant). Only 45.2% correctly identified high-risk body fluids. Sixty-eight
      per cent of anaesthetists knew the appropriate first aid measures to be taken
      following needlestick injury. Only 15% of anaesthetists were aware that post
      exposure prophylaxis (oral medication) should be administered within 1 h of
      injury. This study reveals a surprisingly poor knowledge of high-risk body fluids
      and action to be taken following needlestick injury. Timely post-exposure
      prophylaxis, after needlestick exposure to high-risk body fluids, is believed to
      reduce the risk of seroconversion to HIV. Ignorance of this may increase the risk
      of seroconversion to HIV for anaesthetists and other healthcare professionals.

PMID- 10895755
TI  - Effects of propofol on functional activities of hepatic and extrahepatic
      conjugation enzyme systems.
AB  - The effect of propofol on the hepatic and extrahepatic conjugation enzyme systems
      was assessed in vitro using microsomal and cytosolic preparations of human liver,
      hamster kidney, lung and gut. The functional activities of phase-II enzymes,
      including uridine diphosphate-glucuronosyltransferase (UDPGT), glutathione S
      transferase (GST) and N-acetyltransferase (NAT) were evaluated in the presence of
      various concentrations of propofol (0.05-1.0 mmol litre-1), using 1-naphthol, 1
      chloro-2,4-dinitrobenzene and p-aminobenzoic acid as substrates respectively.
      Propofol produced concentration-dependent inhibition of UDPGT activity in human
      liver microsomes. Propofol did not produce significant inhibition of human
      hepatic GST activity at concentrations below 1.0 mmol litre-1. In contrast, NAT
      activity was unaffected by propofol 0.05-1.0 mmol litre-1 in human liver
      cytosolic preparations. In extrahepatic tissues, hamster renal and intestinal
      UDPGT activities were significantly inhibited by propofol at 0.25-1.0 mmol litre
      1. In these tissues, GST and NAT were unaffected by propofol at 1.0 mmol litre-1.
      Propofol produced differential inhibition of human liver and hamster extrahepatic
      conjugation enzymes as a result of different substrate and tissue specificities.
      The potential interference of the metabolic profile of phase-II enzymes as a
      result of inhibition by propofol (especially of UDPGT and GST) should be
      considered when using propofol with other drugs for anaesthesia.

PMID- 10895756
TI  - Vagally mediated sympathoexcitation and central depression by desflurane in
      rabbits.
AB  - The effects of desflurane on renal sympathetic nerve activity (RSNA) were studied
      in intact or vagotomized anaesthetized rabbits with initial concentrations of 4.5
      18%, subsequently equilibrated to end-tidal concentrations from 3%, 6%, 9% and
      12% each for 20 min allowing sympathetic activity to stabilize. In intact
      animals, immediate transient increases in mean sympathetic activity from 27% to
      63% were closely related to initial concentrations from 4.5% to 18%. During
      subsequent equilibration this remained elevated by 25-30% up to 6%, returned to
      control at 9% and fell by 33% at 12%. Bilateral vagotomy abolished
      sympathoexcitation apart from small increases in sympathetic activity, for
      example 14% at 4.5% (P < 0.05). We conclude that increases in inspired desflurane
      concentrations evoked rapid transient vagally mediated reflex sympathoexcitation
      with a small extra-vagal contribution. Central depression of sympathetic activity
      started at 6% and was 33% below baseline at 12%.

PMID- 10895757
TI  - Volume replacement in the surgical patient--does the type of solution make a
      difference?

PMID- 10895758
TI  - Intravenous clonidine infusion in critically ill children: dose-dependent
      sedative effects and cardiovascular stability.
AB  - Clonidine is used for analgesia and sedation in paediatric anaesthesia, but there
      are no data on its sedative properties and side effects in critically ill
      children. We studied 30 ventilated children aged 10 yr and under to determine an
      effective i.v. dosing range and to assess its cardiovascular effects. Twenty non
      paralysed, ventilated children were given a background infusion of midazolam 50
      micrograms kg-1 h-1 combined with a variable clonidine infusion (0.1-2 micrograms
      kg-1 h-1) to maintain optimal sedation. The effects of clonidine 1 microgram kg-1
      h-1 on cardiac index were measured in 10 postoperative cardiac patients using a
      reverse Fick method. Dose-dependent sedation was achievable (713 out of 861 h)
      without cardiovascular side effects, but an infusion limit of clonidine 1
      microgram kg-1 h-1 was inadequate in two patients. An increased dose limit of 2
      micrograms kg-1 h-1 combined with midazolam 50 micrograms kg-1 h-1 achieved
      satisfactory sedation scores for 602 out of a total of 672 h studied with no
      failures. Clonidine in combination with midazolam at 1 microgram kg-1 h-1 was not
      associated with significant changes in heart rate arterial pressure or cardiac
      index.

PMID- 10895759
TI  - Complications from regional anaesthesia for carotid endarterectomy.
AB  - The complications of carotid endarterectomy (CEA) under cervical plexus blockade
      have yet to be fully evaluated. Two different cases are presented; both patients
      suffered sudden collapse following superficial and deep cervical plexus block in
      preparation for CEA. The causes, presenting signs and differential diagnoses are
      discussed. The safest cervical plexus anaesthetic block technique has not yet
      been established.

PMID- 10895760
TI  - Transthoracic echocardiography for perioperative haemodynamic monitoring.
AB  - Transoesophageal echocardiography (TOE) is valuable for perioperative monitoring
      in patients at risk from haemodynamic disturbance. However, its use is not
      practicable in patients undergoing surgical procedures under regional
      anaesthesia. We describe two cases showing that transthoracic echocardiography
      (TTE) has the same advantages as TOE and thus may be valuable for monitoring
      awake patients. TTE should be considered when extended perioperative haemodynamic
      monitoring is needed but TOE is not possible.

PMID- 10895761
TI  - Successful resuscitation from recurrent ventricular fibrillation secondary to
      butane inhalation.
AB  - Resuscitation from cardiac arrest caused by volatile substance abuse is rarely
      successful. Large doses of catecholamines given during resuscitation, in the
      presence of butane, may cause recurrent ventricular fibrillation. We report a
      case of prolonged resuscitation in a young man who had inhaled butane. Cardiac
      output was restored 10 min after the administration of intravenous amiodarone. We
      suggest that antiarrhythmic agents should be used early during resuscitation to
      prevent recurrent arrhythmias.

PMID- 10895762
TI  - Management of complications of tracheal surgery--a case of dehiscence.
AB  - We report a case of tracheal stenosis in a patient with immune thrombocytopenia
      who presented 4 yr after splenectomy. The 20-yr progression of the stenosis and
      management, including resection, is charted. The period after resection was
      complicated by wound infection, surgical emphysema, mediastinitis and dehiscence
      of the anastomosis of the trachea. The management of patients with tracheal
      lesions is discussed, but concentrates on airway care after tracheal resection
      when complications developed. A laryngeal mask airway was used to stabilize an
      uncuffed tracheal tube at the site of dehiscence.

PMID- 10895763
TI  - Microalbuminuria following anaphylaxis with general anaesthesia.
AB  - Microalbuminuria is increasingly recognized as a marker of pathologies that cause
      acute systemic capillary leak. We report a case of an anaphylactic reaction to
      general anaesthesia involving cardiac arrest. In this case the urinary excretion
      of albumin following resuscitation suggests that severe anaphylaxis is another
      condition for which microalbuminuria is a sensitive monitor.

PMID- 10895764
TI  - Laboratory assessment of the Bird T-Bird VS ventilator performance using a model
      lung.
AB  - We assessed the Bird T-Bird VS ventilator using a model lung constructed to
      standard 10651-1 of the International Standards Organization. We used different
      combinations of lung compliance and airway resistance to simulate normal and
      diseased adult and paediatric lungs. Different preset tidal volumes at various
      respiratory rates were delivered to the model lung and compared with the actual
      measured tidal volumes. The results showed that the delivered tidal volumes were
      within the manufacturer's specification of +/- 10% of the preset tidal volumes in
      normal adult and paediatric combinations of lung compliance and airway
      resistance. The ventilator can be powered by mains electricity supply or battery
      and requires only optional compressed oxygen. The ventilator is suitable for the
      provision of advanced ventilatory support during prolonged patient transfer.

PMID- 10895765
TI  - Recommendations for uniform reporting of data following major trauma--the Utstein
      style. An International Trauma Anaesthesia and Critical Care Society (ITACCS)
      initiative.

PMID- 10895766
TI  - Anaesthesia without anaesthetics--a possible mechanism revisited.

PMID- 10895767
TI  - Inappropriate methods for patient satisfaction.

PMID- 10895768
TI  - EEG-controlled rapid opiate detoxification under general anaesthesia.

PMID- 10895769
TI  - Histaminoid reactions associated with rocuronium.

PMID- 10895770
TI  - Comparison of laryngeal mask and intubating laryngeal mask insertion by the naive
      intubator.

PMID- 10895771
TI  - Severe vasovagal attack during regional anaesthesia for caesarean section.

PMID- 10895772
TI  - Severe vasovagal attack during regional anaesthesia for caesarean section.

PMID- 10895773
TI  - Spinal anaesthesia in children: are we missing the point?

PMID- 10895774
TI  - Effect of continuous epidural 0.2% ropivacaine vs 0.2% bupivacaine on
      postoperative pain, motor block and gastrointestinal function after abdominal
      hysterectomy.

PMID- 10895775
TI  - Hidden hazards of scavenging.

PMID- 10895776
TI  - Contamination of saline.

PMID- 10895777
TI  - Acute dystonia in a 14-yr-old following propofol and fentanyl anaesthesia.

PMID- 10895778
TI  - Laparotomy following femoral venous line insertion.

PMID- 10895779
TI  - Fractured femur in the elderly.

PMID- 10895781
TI  - Multiple authorship.

PMID- 10895780
TI  - Temperature coefficients of the solubilities of inhaled anaesthetics.

PMID- 10895782
TI  - XI International Workshop in Magnetic Resonance Angiography: new aspects on
      visualisation of macro- and microcirculation. Lund, Sweden, September 22-25,
      1999. Abstracts.

PMID- 10895783
TI  - Society for Epidemiologic Research 33rd annual meeting. Seattle, Washington, USA.
      June 15-17, 2000. Abstracts.

PMID- 10895785
TI  - Royal Australasian College of Surgeons annual scientific congress. Melbourne, 7
      12 May 2000. Abstracts.

PMID- 10895784
TI  - Clinical practice guidelines for nutrition in chronic renal failure. K/DOQI,
      National Kidney Foundation.

PMID- 10895786
TI  - Author and keyword indexes for volumes 337-344 (1999).

PMID- 10895788
TI  - British Association of Urological Surgeons annual meeting. Birmingham, United
      Kingdom, 19-23 June 2000. Abstracts.

PMID- 10895787
TI  - European Society for Paediatric Urology 11th annual meeting. Tours, France, 7-10
      June 2000. Abstracts.

PMID- 10895789
TI  - British Society for Haematology annual scientific meeting. Bournemouth, United
      Kingdom, 27-29 March 2000. Abstracts.

PMID- 10895790
TI  - IOS 2000--Imaging, Oncology, Science. Birmingham, United Kingdom, 22-24 May 2000.
      Abstracts.

PMID- 10895791
TI  - Association of Surgeons of Great Britain and Ireland and Surgical Research
      Society millennium meeting. Cardiff, 23-26 May 2000. Abstracts.

PMID- 10895792
TI  - The 1st International Conference on Women, Heart Disease and Stroke. Victoria,
      British Columbia, Canada. May 7-10, 2000. Abstracts.

PMID- 10895793
TI  - 5th International Symposium on Biological Therapy of Cancer: From Basic Research
      to Clinical Applications. Munich, Germany, 27-30 October 1999. Abstracts.

PMID- 10895794
TI  - American Society for Biochemistry and Molecular Biology and American Society for
      Pharmacology and Experimental Therapeutics joint meeting with the French
      Pharmacological Society and the Pharmacological Society of Canada. ASBMB/ASPET
      2000. Boston, Massachusetts, USA. June 4-8, 2000. Abstracts.

PMID- 10895795
TI  - FEBS Letters volumes 442-464 (1999) master index.

PMID- 10895796
TI  - European Conference on Management of Coronary Heart Disease. Nice, France, 17-19
      April 2000. Abstracts.

PMID- 10895797
TI  - The Expert Consensus Guideline Series: Medication Treatment of Bipolar Disorder
      2000.
AB  - OBJECTIVES: New treatments for bipolar disorder have been reported since we first
      published survey-based expert consensus guidelines in 1996. The evidence for
      these treatments varies widely; data are especially limited regarding comparisons
      between treatments and how to sequence them. We therefore undertook a new survey
      of expert opinion in order to bridge gaps between the research evidence and key
      clinical decisions. METHOD: Based on a literature review, a written survey was
      prepared which asked about 1,276 options for psychopharmacologic interventions in
      48 specific clinical situations. Most options were scored using a modified
      version of the RAND Corporation 9-point scale for rating appropriateness of
      medical decisions. We contacted 65 national experts, 58 of whom (89%) completed
      the survey. Consensus on each option was defined as a non-random distribution of
      scores by chi-square test. We assigned a categorical rank (first-line/preferred
      choice, second-line/alternate choice, third-line/usually inappropriate) to each
      option based on the confidence interval of its mean rating. Guideline tables
      indicating preferred treatment strategies were then developed for key clinical
      situations. RESULTS: The expert panel reached consensus on many key strategies,
      including acute and preventive treatment for mania (euphoric, mixed, and
      dysphoric subtypes), depression, and rapid cycling, and approaches to managing
      the complications of treatment resistance and comorbidity. Use of a mood
      stabilizer is recommended in all phases of treatment. Divalproex (especially for
      mixed or dysphoric subtypes) and lithium are the cornerstone choices among this
      class for both acute and preventive treatment of mania. Regardless of which is
      selected first, if monotherapy fails, the next recommended intervention is to use
      these agents in combination. The combination can then serve as the foundation on
      which other medications are added, if needed. Carbamazepine is the leading
      alternative mood stabilizer for mania. Expert opinion regards other new
      anticonvulsants as second-line options (e.g., if the previously mentioned mood
      stabilizers fail or are contraindicated). For milder depression, a mood
      stabilizer, especially lithium, may be used as monotherapy. Divalproex and
      lamotrigine are other first-line choices. For more severe depression, a standard
      antidepressant should be combined with lithium or divalproex. Bupropion,
      selective serotonin reuptake inhibitors (SSRIs), and venlafaxine are preferred
      antidepressants, and should be tapered 2 to 6 months after remission. Divalproex
      monotherapy is recommended for initial treatment of either depression or mania
      with rapid cycling. Antipsychotics are recommended for use with the above
      regimens for mania or depression with psychosis, and as potential adjuncts in non
      psychotic episodes. Atypical antipsychotics, especially olanzapine and
      risperidone, were generally preferred over conventional antipsychotics.
      Recommendations are also given concerning the use of electroconvulsive therapy
      (ECT), clozapine, thyroid hormone, stimulants, and various novel agents for
      patients with treatment-refractory illness. CONCLUSIONS: The experts reached high
      levels of consensus on key steps in treating bipolar disorder despite obvious
      gaps in high-quality data. To evaluate many of the treatment options in this
      survey, the experts had to extrapolate beyond controlled data; however, their
      recommendations are generally conservative. Experts reserve strongest support for
      initial strategies and individual medications for which there are high-quality
      research data, or for which there are longstanding patterns of clinical usage.
      Within the limits of expert opinion and with the understanding that new research
      data may take precedence, these guidelines provide clear pathways for addressing
      common clinical questions in a manner that can be used to inform clinicians and
      educate patients regarding the relative merits of a variety of interventions.

PMID- 10895798
TI  - Transplantation 2000. 1st Joint annual meeting of the American Society of
      Transplant Surgeons and the American Society of Transplantation. Chicago,
      Illinois, USA. May 13-17, 2000. Abstracts.

PMID- 10895799
TI  - [The ICD-9-CM code for oncologic and hemato-oncologic recovery: between rules,
      uncertainty, and discretion: what to do?].

PMID- 10895800
TI  - The structure of the bladder neck, urethra and pelvic floor in relation to female
      urinary continence.

PMID- 10895801
TI  - Gynecologic effects of tamoxifen: case reports and review of the literature.
AB  - The literature regarding the gynecologic effects of tamoxifen contains very
      little data on the vagina and lower urinary tract. The authors present two
      patients receiving tamoxifen who had gynecologic surgery complications that could
      be associated with tamoxifen use. Both patients had poor healing which improved
      when the tamoxifen was discontinued. Possible explanations are given for this
      observation based on what is known about this unusual drug. Owing to the success
      of tamoxifen in breast cancer patients, its use is currently being extended to
      include groups of healthy women at risk for the development of breast cancer.
      Because the number of women receiving tamoxifen may be increasing the authors
      include a review of its effects, with which all health care providers caring for
      women should be familiar.

PMID- 10895802
TI  - TENS: a treatment option for bladder dysfunction.
AB  - To ascertain the mode of action and benefits of transcutaneous electrical nerve
      stimulation (TENS) in detrusor overactivity, stress incontinence and interstitial
      cystitis, an English-language literature search using Medline (1984-1995) was
      undertaken with detrusor instability, incontinence, interstitial cystitis,
      neuromodulation, transcutaneous electrical nerve stimulation and urodynamics as
      keywords and the material so identified was reviewed. The mode of action of TENS
      and optimal stimulation parameters in bladder dysfunction remain unclear. Lack of
      strict selection criteria and deficient reporting of subjective and objective
      outcomes precluded full assessment of therapeutic efficacy. A beneficial effect
      was evident in some studies of detrusor overactivity and interstitial cystitis. A
      trial of TENS in detrusor overactivity and interstitial cystitis refractory to
      conventional therapy would seem justified. Continued experimental research and
      further clinical studies will lead to refinement of the treatment modality.

PMID- 10895803
TI  - Anticholinergic medication for the unstable bladder: prospective trials of
      imipramine/propantheline versus penthienate and oxybutynin versus penthienate.
AB  - A comparison was made of three drug regimens: imipramine
      (Tofranil)/propantheline, oxybutynin (Ditropan) and penthienate bromide
      (Monodral). Two comparative trials were performed in prospective studies, using a
      randomization and cross-over design. All the drugs were found to improve the
      urinary symptoms and urodynamic changes associated with the unstable bladder, but
      penthienate was shown to be more effective than imipramine/propantheline. Its
      effect on the unstable bladder was equivalent to that of oxybutynin. Side-effects
      were common and most common with oxybutynin. However, the inability of these
      drugs to prevent the uninhibited detrusor contractions of the unstable bladder
      consistently and objectively was demonstrated.

PMID- 10895804
TI  - Vaginal axis after abdominal, vaginal and laparoscopic hysterectomy: a
      preliminary study with perineal ultrasonography using contrast medium.
AB  - Fifteen consecutive women (mean age 44.5 years) without pelvic relaxation
      underwent total abdominal (5), vaginal (5) and laparoscopic (5) hysterectomy for
      benign disease. The vaginal axes of the patients were examined prior to and on
      average 7 weeks (range 3-10) after the operation with perineal ultrasonography
      enhanced with an ultrasound contrast medium (SHU454/Echovist-300). Transabdominal
      and vaginal hysterectomies were performed in the classic manner, i.e. the round
      as well as cardinal and sacrouterine ligaments were attached to the vaginal
      vault, followed by peritonealization. In laparoscopic hysterectomy the round,
      broad and outer parts of the uterosacral and the upper parts of the cardinal
      ligaments were desiccated by bipolar electrocoagulation and cut with laparoscopic
      scissors. The vagina was closed by interrupted sutures with no specific fixation
      of the round, cardinal or uterosacral ligaments. Preoperative ultrasound findings
      showed that in all women the vagina was an angulated organ. The mean preoperative
      angle between the upper and lower vaginal portions was 108 degrees, in both the
      supine and the standing positions. Postoperatively this angulated shape remained
      almost unchanged after vaginal (mean angle 117 degrees ) and laparoscopic
      hysterectomy (mean angle 130 degrees ), whereas after transabdominal hysterectomy
      the vaginal axis rotated anteriorly and became an almost straight tube (mean
      angle 158 degrees). We conclude that the vaginal axis, at least at an early stage
      after vaginal and laparoscopic hysterectomy remained in almost the same position
      as preoperatively, in contrast to that after abdominal hysterectomy. A tight
      attachment of the round ligaments to the vaginal vault in the abdominal approach
      could explain the outcome of transabdominal hysterectomy, and should be called
      into question.

PMID- 10895805
TI  - Electrovesicogram in stress urinary incontinence: a preliminary study.
AB  - Electrovesicograms (EVG) were studied in 20 women with stress urinary
      incontinence (SUI) and 12 healthy female volunteers with a mean age of 44.8 and
      48.2 years, respectively. Recordings were performed by means of three electrodes
      applied to the skin in the hypogastric area and one reference electrode to the
      lower limb. In the 12 healthy women pacesetter potentials (PPs) were recorded as
      regular triphasic waves. Of the 20 SUI patients 16 showed normal EVG, and the
      remaining 4 exhibited 'tachyvesica', i.e. increased PP frequency. These 4
      patients proved to have combined urge and stress incontinence with detrusor
      hyperreflexia. It was concluded that SUI patients have normal EVG unless there is
      an associated pathology.

PMID- 10895806
TI  - Postpartum pelvic floor conditioning using vaginal cones: not only for
      prophylaxis against urinary incontinence and descensus.
AB  - Seventy-one women were examined 6-8 weeks after spontaneous delivery by pelvic
      floor (PF) palpation, inspection, manometry and gravimetry. Re-examination was
      performed in the same way after 4-6 weeks of daily cone training. Control groups
      included 20 women prior to and after conventional puerperal exercises, and 8
      nulliparae prior to and after the same cone training, using a five-cone set. The
      number of puerperae not capable of voluntary PF contraction declined from 34%
      before to 6% after training. Optimum initial and post-training responses were
      exhibited by all nulliparae. Differences between cone and conventional exercise
      groups were of minor importance. Contractility increased from 5 to 10 mmHg on
      average in puerperae and from 15 mmHg to 21 mmHg in nulliparae. Cone nos. 1-3
      were most frequently required at the beginning of training, and nos. 3-5 towards
      the end. Cone training works well as an alternative or complement to conventional
      postpartum exercises, and may therefore be recommended especially to puerperae
      who are not capable of holding vaginal cones of 20-70 g 6 weeks after delivery.

PMID- 10895807
TI  - Treatment of refractory interstitial cystitis.
AB  - Interstitial cystitis is the most therapeutically frustrating condition of the
      urinary tract. The vast array of treatments available clearly indicates that none
      is particularly effective. As the majority of patients fail to experience a
      significant and prolonged response to standard treatments, new options are
      frequently being developed. These include the oral administration of cimetidine,
      the intravesical use of hyaluronic acid and BCG, and total cystectomy with the
      formation of a continent urinary diversion. Unfortunately, the acceptance of many
      new treatments is based on incomplete evaluation, and this has resulted in a
      confusing array of disparate alternatives. Effective and durable treatment will
      not be available until the nature of the disease is better understood and the
      mechanisms of action of current therapies are elucidated.

PMID- 10895808
TI  - An algorithm for the management of urinary stress incontinence.
AB  - An algorithm for the management of urinary incontinence in the female is
      presented. The performance of history, physical examination, and simple office
      bladder testing are reviewed. Patients are categorized into a complex group which
      require multi-channel urodynamic testing or a non-complex group which may proceed
      to surgical intervention without such testing. Indications for collagen injection
      and pubo-vaginal sling procedure are discussed.

PMID- 10895809
TI  - The need for standardization of the valsalva leak-point pressure.
AB  - The Valsalva leak-point pressure is a new test being advocated for evaluation of
      urethral sphincter function. However, there is currently no standardized
      technique for performing the test, and therefore it is difficult to draw
      conclusions regarding its ability to define the degree of function or dysfunction
      of the urethral sphincter mechanism. This article reviews the current literature
      regarding the parameters and techniques for performing the Valsalva leak-point
      pressure test. Based on what is known, recommendations for testing parameters and
      conditions under which the test should be performed are provided. This test may
      play a role in the evaluation of the urethral sphincter and give prognostic
      information regarding surgical outcomes, but first the technique for performing
      the test should be standardized and agreed upon. Until this is done no general
      conclusions can be drawn regarding the usefulness of this test in the evaluation
      of the incontinent woman.

PMID- 10895810
TI  - Ureterovaginal fistula following laparoscopic-assisted vaginal hysterectomy--a
      case report with review of literature.
AB  - The authors present a case of ureterovaginal fistula following laparoscopy
      assisted vaginal hysterectomy, which was successfully managed by
      ureteroneocystostomy with bladder psoas hitch.

PMID- 10895811
TI  - Recommendations on functional sonography of the lower female urinary tract.

PMID- 10895812
TI  - Chordoid meningioma: a clinicopathologic study of 42 cases.
AB  - The term chordoid meningiomas was first used by Kepes et al. in 1987 to describe
      a meningeal tumor in young patients associated with microcytic anemia and/of
      dysgammaglobulinemia. Such tumors were composed of spindle or epithelioid cells
      disposed in chordoma-like clusters and cords in a myxoid matrix and often
      featured a prominent lymphoplasmacellular infiltrate. Our study includes 42
      chordoid meningiomas that represented 0.5% of all meningiomas operated at Mayo
      Clinic during the interval 1975 to 1997. The male to female ratio was 1:1 and the
      age range was 12 to 77 years (mean, 47.4 yrs). Only two (5.2%) occurred in
      children. The majority (88%) were large and supratentorial. No manifestation of
      systemic disease was noted. Chordoid elements comprised 10% to 100% of the
      tumors: 34 (81%) were more than 50% chordoid. Thirty-seven tumors (88%) were
      classified as typical and five as atypical. Lymphoplasmacytic infiltrates varied,
      being moderate in 10 cases (23.8%), mild in 15 (35.7%), and absent in 17 (40.5%).
      In 14 (42%) of the 33 cases with available follow up, one or more recurrences
      were noted. All but one recurrent tumor had been subtotally resected. In 86% of
      recurrent tumors, the primary lesion was more than 50% chordoid in pattern and
      contained little or no inflammatory infiltrate. In our experience, chordoid
      meningiomas are primarily tumors of adults, lack sex predilection, are
      unassociated with systemic manifestations, and uniformly recur when subtotally
      excised.

PMID- 10895813
TI  - A clinicopathologic study of 100 cases of pulmonary sclerosing hemangioma with
      immunohistochemical studies: TTF-1 is expressed in both round and surface cells,
      suggesting an origin from primitive respiratory epithelium.
AB  - Pulmonary sclerosing hemangioma (SH) is a lung neoplasm of uncertain histogenesis
      that is composed of two major cell types: surface and round cells. The authors
      studied 100 cases of pulmonary SH that presented as a peripheral (95%), solitary
      (96%) mass of less than 3 cm in diameter (74%) in asymptomatic patients who were
      mostly women (83%) with a mean age of 46.2 years. Immunohistochemistry of
      multiple epithelial, mesothelial, pneumocyte, neuroendocrine, and mesenchymal
      markers was performed on 47 cases to investigate the histogenesis of this
      neoplasm. Both surface and round cells stained with epithelial membrane antigen
      (EMA) and thyroid transcription factor-1 (TTF-1) in more than 90% of cases;
      however, the round cells were uniformly negative for pancytokeratin and positive
      for cytokeratin-7 and CAM 5.2 in only 31% and 17% of cases, respectively.
      Surfactant proteins A and B as well as Clara cell antigen were positive in
      varying numbers of surface cells but they were negative in the round cells.
      Neuroendocrine cells either as isolated scattered cells or as a tumorlet within
      the center of SH were detected (chromogranin, Leu-7, synaptophysin positive) in
      three cases. The expression of TTF-1 in the absence of surfactant proteins A and
      B and Clara cell antigens in the round cells of SH suggests that they are derived
      from primitive respiratory epithelium. The alveolar pneumocytes and
      neuroendocrine cells may either represent phenotypic differentiation of a
      primitive respiratory epithelial component or they may correspond to non
      neoplastic entrapped or hyperplastic elements. The concomitant positivity of both
      cell types in SH for TTF-1 and EMA, and the negativity of round cells for
      pancytokeratin and neuroendocrine markers, provide useful clues not only for
      histogenesis but also for the diagnosis of this lung neoplasm.

PMID- 10895814
TI  - Metanephric stromal tumor: report of 31 cases of a distinctive pediatric renal
      neoplasm.
AB  - We report 31 cases of a novel pediatric renal neoplasm, metanephric stromal tumor
      (MST). Mean patient age was 2 years, and the most common presentation was that of
      an abdominal mass. Gross examination typically revealed a fibrous lesion centered
      in the renal medulla containing smooth-walled cysts (mean tumor size, 5.5 cm).
      MST is histologically identical to the stromal component of metanephric
      adenofibroma (MAF, previously termed nephrogenic adenofibroma) and is an
      unencapsulated spindle cell lesion that entraps native kidney. Characteristic
      histologic features of MST include alternating cellularity that imparts a nodular
      low-power appearance, onion-skin cuffing around entrapped renal tubules,
      heterologous differentiation (glia or cartilage), and vascular alterations
      (angiodysplasia of entrapped arterioles, juxtaglomerular cell hyperplasia in
      entrapped glomeruli). Three tumors in which the vascular alterations were
      particularly florid were associated with extrarenal vasculopathy and attendant
      morbidity. A majority of cases stained for CD34, although the degree of staining
      was variable. Most patients were treated with surgical excision alone, and none
      experienced recurrence or metastasis. Recognition of this entity can spare a
      child potentially toxic adjuvant chemotherapy that might be used for lesions in
      its differential diagnosis, specifically clear cell sarcoma of the kidney.

PMID- 10895815
TI  - Myxoid leiomyosarcoma of soft tissue, an underrecognized variant.
AB  - Myxoid leiomyosarcoma is an uncommon tumor which, although previously well
      described in the uterus, is recognized to a lesser extent at other sites. We
      describe 18 cases of soft tissue leiomyosarcoma in which myxoid stroma occupied
      >50% of the tissue examined. Patients ranged in age from 22 to 84 years old
      (median, 57.5 yrs) and female patients outnumbered male patients 14 to 4. Tumor
      locations included the limbs (6 cases), female external genitalia (4 cases), head
      and neck region (3 cases), chest (2 cases), nipple, paratesticular soft tissue,
      and perineum (one case each). The tumors had a grossly gelatinous appearance and
      adopted three major histologic architectures: fascicular, reticular/microcystic,
      and "myxofibrosarcoma-like." The tumor cells were predominantly spindled in all
      cases with typical features of smooth muscle differentiation; there was a mixture
      of spindle and epithelioid cells in one case. No cases with pure epithelioid
      cytology were seen. All tumors displayed immunoreactivity for smooth muscle
      markers (smooth muscle actin 16/17, desmin 8/18) and, in addition, four cases
      were positive for keratin CAM 5.2 and three for epithelial membrane antigen. The
      tumors had a tendency to be morphologically lower grade (9 tumors were grade I, 8
      were grade II, and only 1 was grade III). Follow up was available in 13 patients
      with a duration of 8 months to 41 years (median, 39 mos), and revealed local
      recurrences (often repeated) in five cases and metastases in two cases. There
      were three tumor-related deaths, of which two were the result of uncontrolled
      local disease. The differential diagnosis of myxoid leiomyosarcoma is broad and
      encompasses both benign and malignant lesions. Accurate diagnosis is critical
      because therapies may differ widely for entities in the differential diagnosis of
      myxoid leiomyosarcoma.

PMID- 10895816
TI  - Molecular detection of the ETV6-NTRK3 gene fusion differentiates congenital
      fibrosarcoma from other childhood spindle cell tumors.
AB  - Congenital fibrosarcoma (CFS) is a pediatric spindle cell tumor of the soft
      tissues that usually presents before the age of 2 years. Although these tumors
      display histologic features of malignancy and frequently recur, they have a
      relatively good prognosis and only rarely metastasize. CFS must therefore be
      differentiated from more aggressive spindle cell sarcomas that occur during
      childhood, particularly adult-type fibrosarcoma (ATFS), which can have an
      identical morphology. CFS must also be distinguished from benign but cellular
      fibroblastic lesions of the same age group, including infantile fibromatosis
      (IFB) and myofibromatosis (MFB). Unfortunately, standard pathologic examination
      often does not differentiate CFS from these other conditions. The authors
      recently identified a novel chromosomal translocation in CFS, t(12;15)(p13;q25),
      which gives rise to an ETV6-NTRK3 gene fusion. They subsequently developed
      reverse transcription-polymerase chain reaction (RT-PCR) assays that can detect
      ETV6-NTRK3 fusion transcripts in CFS frozen or paraffin-embedded tumor specimens.
      To confirm the use of this assay in the differential diagnosis of CFS, they have
      screened a larger series of childhood pediatric spindle cell lesions for ETV6
      NTRK3 gene fusions, including 11 cases of CFS, 13 malignant spindle cell tumors
      (including ATFS), and 38 benign spindle cell tumors (including IFB and MFB). Of
      the 11 cases diagnosed as CFS, 10 showed the ETV6-NTRK3 gene fusion, whereas none
      of the 51 other malignant or benign spindle cell tumors demonstrated this fusion
      gene. They also compared their RT-PCR findings with those of conventional
      cytogenetics and with immunohistochemical detection of the ETV6-NTRK3 protein
      using antisera to NTRK3. They conclude that RT-PCR analysis is superior to these
      techniques for the detection of the ETV6-NTRK3 gene fusion in pediatric spindle
      cell tumors, and it is a reliable and specific modality for the diagnosis of CFS.

PMID- 10895817
TI  - Gastrointestinal stromal tumor versus intra-abdominal fibromatosis of the bowel
      wall: a clinically important differential diagnosis.
AB  - Intra-abdominal fibromatosis (IAF) is an uncommon benign neoplasm that usually
      occurs in the mesentery or retroperitoneum and may, on occasion, mimic a
      gastrointestinal stromal tumor (GIST). Differentiating between these two entities
      is important clinically because IAF is a benign tumor whereas GISTs frequently
      have malignant potential. In this study, the authors identified 13 cases of IAF
      with prominent involvement of the bowel wall as well as 35 GISTs of the small
      intestine, colon, or mesentery and analyzed their clinical, gross, histologic,
      immunophenotypic, and ultrastructural characteristics to identify important
      distinguishing features. Patients with IAF were younger (mean, 34 yrs) than
      patients with GIST (mean, 54 yrs). Both types of tumors tended to be large, but
      GISTs were soft and lobulated with hemorrhage, necrosis, or cystification whereas
      IAFs were firm, tan, and homogeneous. Histologic features characteristic of GIST
      included the presence of spindle or epithelioid cells with variable architecture,
      mitotic activity (range, <1-95 mitoses/50 high-power fields [hpf]; mean, 15
      mitoses/50 hpf), nuclear atypia, and myxoid or hyalinized stroma. Necrosis and
      hemorrhage were seen in 16 and 25 tumors, respectively. In contrast, IAFs were
      composed of broad, sweeping fascicles of monotonous spindle cells with mitotic
      activity (range, <3-11 mitoses/50 hpf; mean, 4 mitoses/50 hpf), bland nuclear
      features, and finely collagenous stroma. Necrosis, hemorrhage, and myxoid
      degeneration were not seen. Immunohistochemical studies performed on a limited
      number of GISTs and IAFs demonstrated that cells expressed vimentin (100% GIST
      and IAF), CD117 (88% GIST and 75% IAF), CD34 (42% GIST and 0% IAF), smooth muscle
      actin (63% GIST and 75% IAF), muscle actin (75% GIST and 75% IAF), desmin (8%
      GIST and 50% IAF), and S-100 protein (16% GIST and 0% IAF). Ultrastructural
      analysis of 21 GISTs revealed incomplete smooth muscle differentiation in some
      tumors whereas IAFs were shown to have complete myofibroblastic/fibroblastic
      differentiation. Information regarding clinical outcome was available on 29
      patients and revealed that three patients with histologically benign GISTs were
      alive with no evidence of disease at 5 months to 6 years (mean, 3.5 yrs) and one
      patient with a histologically benign tumor died of disease after 7 years. Of
      patients with histologically malignant GIST, one died of surgical complications,
      10 were alive without disease at I to 13 years (mean, 5.4 yrs), four were alive
      with disease at 4 months to 15 years (mean, 3.8 yrs), three had disseminated
      disease at operation, and seven were dead of disease at 10 months to 3 years
      (mean, 2.2 yrs). Follow up of eight patients with IAF demonstrated that five were
      alive without disease at 4 months to 15 years (mean, 5.3 yrs) and three had
      recurrences at 1 (two patients) and 2 years (one patient). In summary, IAFs can
      have many features (large size, infiltration of adjacent structures, mitotic
      activity) that can cause diagnostic confusion with GISTs and, importantly, the
      degree of mitotic activity present in IAFs may overlap that seen in malignant
      GISTs. These entities can be distinguished primarily by their light microscopic
      and ultrastructural features but there is a notable overlap in their
      immunohistochemical profiles. The distinction between these neoplasms is
      important because there are important clinical implications for the patient.

PMID- 10895818
TI  - Mixed epithelial and stromal tumor of the kidney.
AB  - We describe the clinicopathologic features of 12 patients with a distinctive
      tumor of the kidney characterized by a mixture of epithelial and stromal elements
      that form solid and cystic growth patterns. Similar tumors were reported
      previously in the literature under various names, including adult mesoblastic
      nephroma. All but one of the patients were women. The only man had a long history
      of treatment with lupron and diethylstilbesterol. Seven of the women had
      histories of long-term oral estrogen use of whom six had undergone total
      abdominal hysterectomy and bilateral salpingo-oophorectomy several years prior,
      and the seventh patient had been using oral contraceptives for many years.
      Another woman had this operation but did not receive any hormone therapy. Ages
      ranged from 31 to 71 years (mean, 56 yrs). Six patients presented with symptoms,
      including pain and infections attributable to mass effect, and in six the tumor
      was detected incidentally. Grossly, the tumors were well-circumscribed (mean
      size, 6 cm; range, 3-12 cm) and consisted of solid and cystic components, most
      often in equal proportions but in variable distribution. Microscopically, the
      spindle cell component ranged in appearance from scar-like fibrous tissue to
      leiomyoma-like interlacing fascicles; usually there was a mixture of both. More
      cellular foci reminiscent of ovarian stroma or solitary fibrous tumor were also
      present. No blastema was present. Epithelial elements (composed of clusters of
      tubules with variable lining) were scattered amidst the spindle cells, and
      focally transformed into large cysts lined by cells with abundant pink cytoplasm
      and a hobnail appearance. Immature epithelial elements typical of Wilms' tumor
      were not present. Muscle markers (desmin and smooth muscle actin) were positive
      diffusely and strongly in the spindle cells of all tumors, whereas HMB-45 and
      CD34 were absent. Estrogen receptors were detected in the nuclei of spindle cells
      in seven tumors and progesterone receptors in three. The distinctive
      clinicopathologic characteristics of these lesions warrant their classification
      as a separate category of kidney tumor. We suggest the descriptive term "mixed
      epithelial and stromal tumor" for this group until its nature and relationship to
      other kidney lesions are further clarified. Its preponderance in females with a
      history of long-term estrogen replacement and the history of long-term sex
      steroid use in the only male patient, combined with the frequent content of
      estrogen and progesterone receptors in the spindle cells, suggest that the
      hormonal milieu plays a role in the evolution of these tumors. The clinical and
      pathologic parallels with mucinous cystic tumors of pancreas and liver raise the
      possibility of a common pathogenetic mechanism that may be linked to the
      periductal fetal mesenchyme. We think this entity is a benign composite neoplasm
      in which stroma and epithelium are both integral neoplastic components.

PMID- 10895819
TI  - Orbital and extraorbital giant cell angiofibroma: a giant cell-rich variant of
      solitary fibrous tumor? Clinicopathologic and immunohistochemical analysis of a
      series in favor of a unifying concept.
AB  - The clinicopathologic and immunohistochemical features of one orbital and nine
      extraorbital soft tissue lesions, the morphology of which overlaps with giant
      cell angiofibroma and solitary fibrous tumor, are presented. There were 3 male
      and 7 female patients. Age at diagnosis ranged from 18 to 81 years (median: 45
      yrs). Development of a mass was the main presenting symptom. For two patients,
      the lesion had been evident for several years before excision. Extraorbital
      tumors were located in the head and neck area (3), back (3), retroperitoneum (1),
      hip (1), and vulva (1). Tumor size ranged from 1.3 cm to 11 cm (median: 4.5 cm).
      The lesions presented grossly as well-demarcated, unencapsulated soft tissue
      masses. Histologically, they were characterized by the presence of alternating
      cellular and sclerosing areas, keloidal collagen deposition, round- to staghorn
      shaped, thick-walled vessels and multinucleated giant stromal cells often lining
      pseudovascular spaces. Cellular areas were composed of non-atypical spindle to
      round cells set in a variably collagenous background. Mitotic activity ranged
      from 1 to 3 mitoses/10 high-power fields. Immunohistochemical studies showed
      positive staining of the spindle/round cells and multinucleated stromal cells
      invariably for vimentin, CD34, CD99, and mostly for bcl-2 but negative for muscle
      specific actin, desmin, CD31, CD117 (c-kit), and inhibin. Occasionally, focal
      reactivity was observed for smooth muscle actin, S-100 protein, epithelial
      membrane antigen, and keratin. Treatment consisted of simple tumorectomy in eight
      patients and wide excision in two. Follow-up information for eight patients
      (range: 7-32 mos; median: 14 mos), including four with microscopically positive
      surgical margins, showed no recurrence. These lesions share the clinical,
      pathologic, and immunohistochemical features of giant cell angiofibroma and
      solitary fibrous tumor, supporting the view that these tumors are closely
      related. In addition, it shows that giant cell angiofibroma occurs equally in
      both sexes and has a wider distribution than initially thought, developing even
      more often in extraorbital locations than in the orbit.

PMID- 10895820
TI  - Grading the invasive component of urothelial carcinoma of the bladder and its
      relationship with progression-free survival.
AB  - Although grading is valuable prognostically in pTa and pT1 papillary urothelial
      carcinoma, it is unclear whether it provides any prognostic information when
      applied to the invasive component in muscle-invasive carcinoma. The authors
      analyzed 93 cases of muscle-invasive urothelial carcinoma of the bladder treated
      with radical cystectomy for which follow-up information was available. Each case
      was graded using the Malmstrom grading system for urothelial carcinoma, applied
      to the invasive component. Pathologic stage, lymph node status, and histologic
      invasion pattern were also recorded and correlated with progression-free
      survival. Thirty-four cases (37%) were pT2, 40 (43%) were pT3, and 19 (20%) were
      pT4. Of the 77 patients who had a lymph node dissection at the time of
      cystectomy, 34 (44%) had metastatic carcinoma to one or more lymph nodes. The
      median survival for pT2, pT3, and pT4 stages was 85, 24, and 29 months,
      respectively (p = 0.0001). Lymph node-negative and lymph node-positive patients
      had a median survival of 63 and 23 months, respectively (p = 0.0001). Fifteen
      patients (16%) were graded as 2b and 78 patients (84%) were graded as 3. Median
      survival of patients graded as 2b was 34 months compared with 31 months for
      patients graded as 3 (p value not significant). Three invasive patterns were
      recognized: nodular (n = 13, 14%), trabecular (n = 39, 42%), and infiltrative (n
      = 41, 44%). The presence of any infiltrative pattern in the tumor was associated
      with a median survival of 29 months, compared with 85 months in tumors without an
      infiltrative pattern (p = 0.06). Pathologic T stage and lymph node status remain
      the most powerful predictors of progression in muscle-invasive urothelial
      carcinoma. In this group of patients histologic grade, as defined by the
      Malmstrom system and as applied to the invasive component, provided no additional
      prognostic information. An infiltrative growth pattern may be associated with a
      more dismal prognosis.

PMID- 10895821
TI  - Extensively necrotic cystic renal cell carcinoma: a clinicopathologic study with
      comparison to other cystic and necrotic renal cancers.
AB  - Renal cell carcinomas often show varying degrees of necrosis and cystic change.
      The prognostic importance of necrosis so extensive that only a few tumor cells
      can be identified is not clear. We gathered clinicopathologic and follow-up data
      on a group of eight such cases ("type I"). These patients were compared with two
      other groups of renal cell carcinomas: those with extensive necrosis (>50%), yet
      with readily identifiable tumor ("type II"), and cancers with extensive cystic
      change not resulting from necrosis, usually multiloculated ("type III"). The
      groups showed similar demographic characteristics, and within each group there
      was great variation in tumor size. Conventional (clear cell) histology was more
      common than papillary morphology in all groups. The type II neoplasms tended to
      be of higher nuclear grade and pathologic stage than the other groups. While one
      of six type I patients with follow up progressed 131 months after diagnosis,
      eight of 20 type II patients showed progression. None of the six type III
      patients with follow up progressed. We conclude that renal cell carcinomas
      showing extensive necrosis are capable of aggressive behavior, and patients with
      these lesions cannot be assured of cure following surgery. Pathologists must be
      aware of this entity and extensively sample any renal lesion showing extensive
      necrosis. The tumors showing a greater amount of viable neoplastic cells yet at
      least 50% necrosis had a higher rate of progression than did the type I patients.
      The lack of progression of any of the type III cases supports the idea that type
      III multiloculated cystic renal cell carcinomas may carry a distinctly better
      prognosis than other forms of renal cell carcinoma.

PMID- 10895822
TI  - Indeterminate fibrohistiocytic lesions of the skin: is there a spectrum between
      dermatofibroma and dermatofibrosarcoma protuberans?
AB  - Routine histology and immunohistochemistry can usually distinguish dermatofibroma
      (DF) and dermatofibrosarcoma protuberans (DFSP). DF generally expresses factor
      XIIIa whereas DFSP generally expresses CD34. The authors report 10 cutaneous
      fibrohistiocytic lesions combining clinical, histologic, and immunohistochemical
      features of both DF and DFSP. The lesions had an average size of 1.2 cm (range,
      0.4-2.7 cm), and occurred on the trunk (n = 6), extremities (n = 3), and face (n
      = 1) of four men and six women (average age, 30.6 yrs; age range, 15-50 yrs).
      Eight lesions exhibited acanthosis and densely cellular fascicles with focal
      storiform areas. All had keloidal collagen, infiltrated the subcutis in a
      honeycomb pattern, and had low mitotic counts (0 to 4 mitoses per square
      millimeter). All were diffusely immunoreactive for factor XIIIa (30%-60% of the
      neoplastic cells) as well as CD34 (20%-70%). This series raises the possibility
      of a biologic spectrum between DF and DFSP; however, double-immunolabeling
      studies showed no notable coexpression of factor XIIIa and CD34 by individual
      cells, suggesting coexistence of two different cellular populations. After an
      average follow up of 22.3 months (range, 10-46 mos) in six cases, a single
      recurrence was documented. The ambiguous histologic features and the potential
      for local recurrence suggest that performing a complete excision may be prudent
      in these diagnostically indeterminate lesions.

PMID- 10895823
TI  - Bile duct apoptosis and cholestasis resembling acute graft-versus-host disease
      after autologous hematopoietic cell transplantation.
AB  - BACKGROUND: Acute graft-versus-host disease (GVHD) of the liver is a frequent
      complication of allogeneic hematopoietic cell transplantation. This report
      describes hepatic GVHD following autologous transplantation. METHODS: We reviewed
      116 consecutive autologous transplant recipients. A diagnosis of GVHD was based
      on histology (segmental to subtotal destruction of bile ductal epithelial cells
      with apoptosis and lymphocytic infiltrates), clinical criteria (elevated serum
      alkaline phosphatase), a response to immunosuppressive therapy, and finding no
      other cause for cholestatic liver disease. RESULTS: Two patients developed
      cholestatic liver disease (alkaline phosphatase levels over five times the normal
      upper limit) and had liver biopsies showing apoptotic and dysmorphic ductular
      epithelial cells typical of GVHD. Three additional patients developed cholestasis
      and intestinal symptoms but had gastric biopsies only, showing apoptotic crypt
      epithelial cells and crypt cell drop-out typical of GVHD. CONCLUSION: Two
      recipients of autologous hematopoietic cells developed histologic abnormalities
      of small bile ducts and cholestatic liver disease resembling GVHD of the liver
      after allogeneic transplant. The mechanisms of bile duct damage in this setting
      may involve immune dysregulation related to reconstitution of immunity with
      peripheral blood stem cells.

PMID- 10895824
TI  - Histochemical and immunohistochemical characterization of foamy histiocytes
      (muciphages and xanthelasma) of the rectum.
AB  - Despite being relatively common in the rectum, foamy histiocytes have received
      scant attention as to the antecedent lesion that causes them to form or their
      histologic characterization on the types of muco-substances they accumulate. One
      hundred consecutive tissue sections of the rectum from an equal number of
      patients were reviewed for the presence of foamy histiocytes, evaluated for their
      associated histologic features, and examined histochemically for five types of
      mucin. Immunohistochemical and electron microscopic studies were performed. Forty
      (40%) of the rectal biopsy tissues contained foamy histiocytes. Patients
      presented with diarrhea, hematochezia, intestinal habit change, constipation,
      hemorrhoids, and abdominal pain. Endoscopically, 19 patients were thought to have
      rectal nodules or polyps. Histologically, 25 of the patients had regenerative
      changes in the adjacent mucosa and 14 had hyperplastic changes. In 36 patients
      (90%), the foamy histiocytes were located superficially in the lamina propria.
      Associated changes indicated that they are found in areas that are subject to an
      injury that is in a healing phase. These changes included mild fibrosis and
      chronic inflammation of lamina propria with mild architectural distortion. Thirty
      five (88%) cases showed staining for D-PAS, Alcian blue stain pH 2.5, and the
      cocktail Alcian blue stain/PAS. Mucicarmine was positive in 25 (63%) cases. The
      Alcian blue stain pH 1.0 was positive in 19 (59%) of 32 cases. Ultrastructural
      studies showed electron-dense globules. Two cases were histologically identical
      to the other 38 but they did not stain for any mucin. Ultrastructural features
      disclosed clear vacuoles and thus represent a xanthelasma of the rectum. The
      foamy cells in all cases were confirmed to be histiocytes by immunohistochemistry
      and electron microscopy. Although muciphages and xanthelasma of the rectum may
      mimic polyps endoscopically, they are not related to any specific symptom or
      clinical finding, despite the fact that they probably represent remnants of a
      previous injury. Muciphages contain neutral, weakly acidic or strongly acidic
      mucin. The main type of acidic mucin is sialomucin with a smaller component of
      sulfated mucin.

PMID- 10895825
TI  - Effect of formalin tissue fixation and processing on immunohistochemistry.
AB  - Although immunohistochemistry is routinely performed by many pathology
      laboratories, its standardization still lags behind. A major cause of variation
      in the reproducibility of immunohistochemical staining is induced by tissue
      fixation and, to a lesser degree, tissue processing. This report, stemming from
      the first meeting of the International Consensus Group on Standardization and
      Quality Control (ICGSQC) in Nice, France, summarizes the problem and suggests
      solutions to begin to achieve standardization of fixation and processing. Most
      laboratories use neutral-buffered formalin (10%) for tissue fixation which
      introduces cross-links, whereas coagulative fixatives are less popular. Problems
      with formalin fixation comprise delay of fixation and variations in the duration
      of the fixation mainly. Solutions to these problems could be to start fixation
      soon (<30 min) after surgical removal of the tissue and to avoid overfixation
      (>24-48 hrs). For tissue processing, the most important problem is inadequate
      tissue dehydration prior to paraffin embedding. This can be prevented by
      preparing all solutions freshly every week, depending on the volume of tissue
      processed. If consistently applied, these procedures could eliminate some of the
      sources of variation in immunohistochemical stains.

PMID- 10895826
TI  - Extraskeletal myxoid chondrosarcoma with neuroendocrine differentiation: a
      pathologic, cytogenetic, and molecular study of a case with a novel translocation
      t(9;17)(q22;q11.2).
AB  - A case of extraskeletal myxoid chondrosarcoma (EMC) in which there was
      histochemical, immunohistochemical, and ultrastructural evidence of
      neuroendocrine differentiation is reported. Genetic investigations showed the
      recently described novel translocation t(9;17)(q22;q11.2) and associated fusion
      of the CHN and RBP56 genes, contrasting with the translocation t(9;22)(q22;q12)
      and EWS/CHN gene fusion found in the majority of EMCs.

PMID- 10895827
TI  - Hepatosplenic alphabeta T-cell lymphoma: an unusual case with clinical,
      histologic, and cytogenetic features of gammadelta hepatosplenic T-cell lymphoma.
AB  - Hepatosplenic gammadelta T-cell lymphoma is a recently identified entity in which
      lymphoma cells bearing the gammadelta T-cell receptor (TCR) infiltrate the
      sinusoids of the liver and the sinuses of the splenic red pulp and bone marrow,
      without lymph node involvement. It is also characterized by a recurrent
      cytogenetic finding, isochromosome 7q (i7q10). The authors report a case of
      hepatosplenic lymphoma of alphabeta T-cell phenotype that shares the same
      clinical, histologic, and cytogenetic characteristics of the previously described
      hepatosplenic gammadelta T-cell lymphoma. Fluorescent in situ hybridization
      performed with chromosome 7 probes showed the typical pattern of isochromosome
      7q. Genomic analysis of the TCR gamma locus failed to detect a clonal
      rearrangement. This unique case of hepatosplenic lymphoma of alphabeta T-cell
      phenotype supports the possibility that lymphoid populations of different
      alphabeta or gammadelta phenotype that share similar homing and presumably
      functional properties could give rise to lymphomas displaying similar clinical
      and pathologic findings.

PMID- 10895828
TI  - Nodular desmoplastic variant of trichoblastoma.

PMID- 10895829
TI  - Anatomic pathology image capture using a consumer-type digital camera.

PMID- 10895830
TI  - Unique cytologic and chromosome aberrations in chondroid lipoma.

PMID- 10895831
TI  - Heterogeneity of Kaposi's sarcoma-associated herpesvirus (HHV-8)-positive
      effusions.

PMID- 10895832
TI  - Primary prevention of type 2 diabetes in high-risk populations.

PMID- 10895833
TI  - Cardiovascular and metabolic benefits of ACE inhibition: moving beyond blood
      pressure reduction.

PMID- 10895834
TI  - Risk-adjusted quality of care rating for diabetes: ready for prime time?

PMID- 10895835
TI  - The 10-g monofilament: the diagnostic divining rod for the diabetic foot?

PMID- 10895836
TI  - Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in
      patients with type 2 diabetes.
AB  - OBJECTIVE: To assess whether ACE inhibitors are superior to alternative agents
      for the prevention of cardiovascular events in patients with hypertension and
      type 2 diabetes. RESEARCH DESIGN AND METHODS: This study is a review and meta
      analysis of randomized controlled trials that included patients with type 2
      diabetes and hypertension who were randomized to an ACE inhibitor or an
      alternative drug, were followed for > or =2 years, and had adjudicated
      cardiovascular events. RESULTS: A total of 4 trials were eligible. The
      Appropriate Blood Pressure Control in Diabetes (ABCD) trial (n = 470) compared
      enalapril with nisoldipine, the Captopril Prevention Project (CAPPP) (n = 572)
      compared captopril with diuretics or beta-blockers, the Fosinopril Versus
      Amlodipine Cardiovascular Events Trial (FACET) (n = 380) compared fosinopril with
      amlodipine, and the U.K. Prospective Diabetes Study (UKPDS) (n = 758) compared
      captopril with atenolol. The cumulative results of the first 3 trials showed a
      significant benefit of ACE inhibitors compared with alternative treatments on the
      outcomes of acute myocardial infarction (63% reduction, P < 0.001),
      cardiovascular events (51% reduction, P < 0.001), and all-cause mortality (62%
      reduction, P = 0.010). These findings were not observed in the UKPDS. The ACE
      inhibitors did not appear to be superior to other agents for the outcome of
      stroke in any of the trials. None of the findings were explained by differences
      in blood pressure control. CONCLUSIONS: Compared with the alternative agents
      tested, ACE inhibitors may provide a special advantage in addition to blood
      pressure control. The question of whether atenolol is equivalent to captopril
      remains open. Conclusive evidence on the comparative effects of antihypertensive
      treatments will come from large prospective randomized trials.

PMID- 10895837
TI  - Delay in onset of awareness of acute hypoglycemia and of restoration of cognitive
      performance during recovery.
AB  - OBJECTIVE: To examine the time course for the onset of, and recovery from, acute
      hypoglycemia in healthy subjects. RESEARCH DESIGN AND METHODS: Eight healthy male
      volunteers were studied on 2 occasions in random order using a hyperinsulinemic
      (1.5 mU x kg(-1) x min(-1)) glucose clamp technique. During control studies,
      euglycemia (5.01 +/- 0.02 mmol/l) was maintained for 225 +/- 3 min. On the other
      occasion, after a euglycemic baseline period, arterialized plasma glucose was
      allowed to fall rapidly to 2.65 +/- 0.02 mmol/l, then maintained at this nadir
      for 90 min before euglycemia was rapidly restored. RESULTS: Cognitive function
      assessed by a battery of sensitive tests (4-choice reaction time, Stroop word,
      and color-word test) became impaired immediately at onset of hypoglycemia (P <
      0.05 for all in the hypoglycemic study vs. those in the euglycemic study).
      Counterregulatory hormone responses (epinephrine, norepinephrine, glucagon,
      cortisol, and growth hormone) and symptomatic awareness of hypoglycemia (assessed
      by a questionnaire) were relatively delayed, being detected 20 min after the
      onset of hypoglycemia. There was no diminution (adaptation) of any responses,
      cognitive, humoral, or symptomatic, during sustained hypoglycemia. During
      recovery, the 4-choice reaction time continued to be abnormal even after
      resolution of symptomatic awareness (P = 0.025). CONCLUSIONS: During
      hypoglycemia, cognitive performance may become impaired before symptomatic
      awareness. During recovery from hypoglycemia, recovery of cognitive function lags
      behind the restoration of glucose levels and resolution of symptoms. Our findings
      have implications for the design of studies examining experimental hypoglycemia
      and need to be investigated in people with diabetes.

PMID- 10895838
TI  - Reduced prevalence of impaired glucose tolerance and no change in prevalence of
      diabetes despite increasing BMI among Aboriginal people from a group of remote
      homeland communities.
AB  - OBJECTIVE: To examine trends in glucose tolerance and coronary risk among
      Aboriginal people from a group of homeland communities in central Australia
      during a 7-year follow-up period. RESEARCH DESIGN AND METHODS: Community-based
      screenings of adult volunteers were performed in 1988 (n = 437; 93% response
      rate) and in 1995 (n = 424; 85% response rate). A health promotion intervention
      program commenced after the 1988 survey that focused on the benefits of exercise
      and appropriate diet. RESULTS: Mean (95% CI) BMI increased significantly from
      22.8 kg/m2 (22.3-23.2) to 24.2 kg/m2 (23.8-24.7) during the follow-up period (P <
      0.001). This increase was similar for men and women and across all age-groups.
      The increase in BMI was greater among subjects residing adjacent to a store
      compared with those residing in communities located far from a store (P < 0.001).
      Decreases were evident in the prevalence of impaired glucose tolerance (IGT)
      (from 22.5 to 10.1% among women, P < 0.001; from 12.2 to 6.5% among men, P =
      0.074) and hypercholesterolemia (from 36.7 to 25.8% among women, P < 0.01; from
      52.4 to 44.0% among men, P = 0.147), but no change was evident in the prevalence
      of diabetes. Smoking remained rare among women (<4%) and decreased among men
      (from 52.9 to 40.8%, P < 0.05). CONCLUSIONS: The trends in glucose intolerance
      were clearly better than have been observed in other Aboriginal communities. The
      institution of an intervention program corresponded with reductions in the
      prevalence of IGT, hypercholesterolemia, and smoking. The prevalence of diabetes
      remained unaltered despite a significant increase in mean BMI, possibly because
      of the promotion of increased physical activity levels.

PMID- 10895839
TI  - Long-term follow-up of infants of mothers with type 1 diabetes: evidence for
      hereditary and nonhereditary transmission of diabetes and precursors.
AB  - OBJECTIVE: To estimate the impact of type 1 diabetes during pregnancy on
      transgenerational genetically caused and/or fuel-mediated amplification of types
      1 and 2 diabetes and to estimate the impact of elevated amniotic fluid insulin
      levels. RESEARCH DESIGN AND METHODS: A total of 75 white offspring of type 1
      diabetic mothers and 49 control subjects of similar age and pubertal stage were
      examined at 5-15 years of age. All offspring had an oral glucose tolerance test.
      Glucose, insulin, and C-peptide were measured at 0, 30, 60, and 120 min after
      loading. Lipids and autoimmune antibodies were measured in fasting plasma.
      RESULTS: Of the 75 offspring, 4 (5.3%) had overt diabetes, and 16 of 71 (22.5%)
      had autoimmune antibodies. Offspring of diabetic mothers had significantly higher
      BMI; symmetry indexes; cholesterol, glucose, insulin, and C-peptide levels; and
      insulin resistance than control subjects. With the exception of cholesterol,
      these values were significantly elevated in offspring who had elevated amniotic
      fluid insulin levels (>8 microU/ml, >48 pmol/l) during pregnancy compared with
      normoinsulinemic offspring and control subjects. CONCLUSIONS: Offspring of type 1
      diabetic mothers have an increased risk for diabetes later in life. The relative
      risk for type 1 and type 2 diabetes is 71.6 and 3.2, respectively. Type 2
      diabetes-associated risk factors, such as high BMI; elevated glucose, insulin,
      and C-peptide levels; and insulin resistance, are related to the fetal metabolic
      experience in utero, as reflected by amniotic fluid insulin concentration.

PMID- 10895840
TI  - Sex differences in the association of endogenous sex hormone levels and glucose
      tolerance status in older men and women.
AB  - OBJECTIVE: Some evidence suggests an inverse association between type 2 diabetes
      and androgens in men and a positive association between type 2 diabetes and
      androgens in women. The purpose of this community-based study was to evaluate sex
      differences in the association between endogenous total and bioavailable estrogen
      and testosterone levels and glucose tolerance status. RESEARCH DESIGN AND
      METHODS: We included in this study 775 men and 633 postmenopausal non-estrogen
      using women, all > or =55 years of age (mean ages 72 and 75 years, respectively).
      A 75-g oral glucose tolerance test (OGTT) was administered to fasting subjects
      from 1984 to 1987, when sera were frozen for measurement of total and
      bioavailable hormone levels. Total testosterone and estradiol levels were
      measured by radioimmunoassay, and bioavailable hormone levels were determined
      using a modified ammonium-sulfate precipitation method. The association between
      steroid hormones and glucose tolerance status was tested. RESULTS: In sex
      specific age- and BMI-adjusted analyses, men with impaired glucose tolerance
      (IGT) had significantly lower total testosterone levels. Women with IGT or type 2
      diabetes had significantly higher bioavailable testosterone and total and
      bioavailable estradiol levels than those with normal glucose tolerance. Total
      testosterone and fasting plasma glucose were inversely associated in men (P =
      0.0001), whereas bioavailable testosterone and estradiol were positively
      associated with fasting plasma glucose in women (P = 0.0001 and 0.001,
      respectively). CONCLUSIONS: Additional studies are needed to further develop the
      hormone-diabetes connection.

PMID- 10895841
TI  - Performance status of health care facilities changes with risk adjustment of
      HbA1c.
AB  - OBJECTIVE: To develop a risk adjustment method for HbA1c, based solely on
      administrative data and to determine the extent to which risk-adjusted HbA1c
      changes the identification of high- or low-performing medical facilities.
      RESEARCH DESIGN AND METHODS: Through use of pharmacy records, 204,472 diabetic
      patients were identified for federal fiscal year 1996 (FY96). Complete
      information (HbA1c levels, demographic data, inpatient records, outpatient
      pharmacy utilization records) was available on 38,173 predominantly male patients
      from 48 Veterans Health Administration (VHA) medical facilities. Hierarchical
      mixed-effects models were used to estimate risk-adjusted unique facility-level
      HbA1c. RESULTS: Predicted HbA1c demonstrated expected patterns for major factors
      known to influence glycemic control. Poorer glycemic control was seen in
      minorities and patients with greater disease severity, longer duration of disease
      (using treatment type or presence of amputation as surrogates), and more
      extensive comorbidity (measured by an adapted Charlson index). Better glycemic
      control was seen in Caucasians, older diabetic patients, and patients with higher
      outpatient utilization. The number of performance outliers was reduced as a
      result of risk adjustment. For mean HbA1c levels, 7 facilities that were
      initially identified as statistically significant outliers were no longer
      outliers after risk adjustment. For high-risk HbA1c (>9.5%) rates, 12 facilities
      that were initially identified as statistically significant outliers were no
      longer outliers after risk adjustment. CONCLUSIONS: Risk adjustment using only
      administrative data resulted in substantial changes in identification of high or
      low performers compared with non-risk-adjusted HbA1c. Although our findings are
      exploratory, risk adjustment using administrative data may be a necessary and
      achievable step in quality assessment of diabetes care measured by rates of high
      risk HbA1c (>9.5%).

PMID- 10895842
TI  - Influences on day-to-day self-management of type 2 diabetes among African
      American women: spirituality, the multi-caregiver role, and other social context
      factors.
AB  - OBJECTIVE: Many African-American women are affected by diabetes and its
      complications, and culturally appropriate lifestyle interventions that lead to
      improvements in glycemic control are urgently needed. The aim of this qualitative
      study was to identify culturally relevant psychosocial issues and social context
      variables influencing lifestyle behaviors--specifically diet and physical
      activity--of southern African-American women with diabetes. RESEARCH DESIGN AND
      METHODS: We conducted 10 focus group interviews with 70 southern African-American
      women with type 2 diabetes. Group interviews were audiotaped and transcripts were
      coded using qualitative data analysis software. A panel of reviewers analyzed the
      coded responses for emerging themes and trends. RESULTS: The dominant and most
      consistent themes that emerged from these focus groups were 1) spirituality as an
      important factor in general health, disease adjustment, and coping; 2) general
      life stress and multi-caregiving responsibilities interfering with daily disease
      management; and 3) the impact of diabetes manifested in feelings of dietary
      deprivation, physical and emotional "tiredness," "worry," and fear of diabetes
      complications. CONCLUSIONS: Our findings suggest that influences on diabetes self
      management behaviors of African-American women may be best understood from a
      sociocultural and family context. Interventions to improve self-management for
      this population should recognize the influences of spirituality, general life
      stress, multi-caregiving responsibilities, and the psychological impact of
      diabetes. These findings suggest that family-centered and church-based approaches
      to diabetes care interventions are appropriate.

PMID- 10895843
TI  - Depression and poor glycemic control: a meta-analytic review of the literature.
AB  - OBJECTIVE: Depression is common among patients with diabetes, but its
      relationship to glycemic control has not been systematically reviewed. Our
      objective was to determine whether depression is associated with poor glycemic
      control. RESEARCH DESIGN AND METHODS: Medline and PsycINFO databases and
      published reference lists were used to identify studies that measured the
      association of depression with glycemic control. Meta-analytic procedures were
      used to convert the findings to a common metric, calculate effect sizes (ESs),
      and statistically analyze the collective data. RESULTS: A total of 24 studies
      satisfied the inclusion and exclusion criteria for the meta-analysis. Depression
      was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001). The
      standardized ES was in the small-to-moderate range (0.17) and was consistent, as
      the 95% CI was narrow (0.13-0.21). The ES was similar in studies of either type 1
      or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and
      diagnostic criteria rather than self-report questionnaires were used to assess
      depression (ES 0.28 vs. 0.15). CONCLUSIONS: Depression is associated with
      hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are
      needed to establish the directional nature of this relationship and to determine
      the effects of depression treatment on glycemic control and the long-term course
      of diabetes.

PMID- 10895844
TI  - The summary of diabetes self-care activities measure: results from 7 studies and
      a revised scale.
AB  - OBJECTIVE: To review reliability, validity, and normative data from 7 different
      studies, involving a total of 1,988 people with diabetes, and provide a revised
      version of the Summary of Diabetes Self-Care Activities (SDSCA) measure. RESEARCH
      DESIGN AND METHODS: The SDSCA measure is a brief self-report questionnaire of
      diabetes self-management that includes items assessing the following aspects of
      the diabetes regimen: general diet, specific diet, exercise, blood-glucose
      testing, foot care, and smoking. Normative data (means and SD), inter-item and
      test-retest reliability, correlations between the SDSCA subscales and a range of
      criterion measures, and sensitivity to change scores are presented for the 7
      different studies (5 randomized interventions and 2 observational studies).
      RESULTS: Participants were typically older patients, having type 2 diabetes for a
      number of years, with a slight preponderance of women. The average inter-item
      correlations within scales were high (mean = 0.47), with the exception of
      specific diet; test-retest correlations were moderate (mean = 0.40). Correlations
      with other measures of diet and exercise generally supported the validity of the
      SDSCA subscales (mean = 0.23). CONCLUSIONS: There are numerous benefits from
      standardization of measures across studies. The SDSCA questionnaire is a brief
      yet reliable and valid self-report measure of diabetes self-management that is
      useful both for research and practice. The revised version and its scoring are
      presented, and the inclusion of this measure in studies of diabetes self
      management is recommended when appropriate.

PMID- 10895845
TI  - Development and validation of a questionnaire to evaluate patient satisfaction
      with diabetes disease management.
AB  - OBJECTIVE: To develop a reliable and valid questionnaire to measure patient
      satisfaction with diabetes disease management programs. RESEARCH DESIGN AND
      METHODS: Questions related to structure, process, and outcomes were categorized
      into 14 domains defining the essential elements of diabetes disease management.
      Health professionals confirmed the content validity. Face validity was
      established by a patient focus group. The questionnaire was mailed to 711
      patients with diabetes who participated in a disease management program. To
      reduce the number of questionnaire items, a principal components analysis was
      performed using a varimax rotation. The Scree test was used to select significant
      components. To further assess reliability and validity; Cronbach's alpha and
      product-moment correlations were calculated for components having > or =3 items
      with loadings >0.50. RESULTS: The validated 73-item mailed satisfaction survey
      had a 34.1% response rate. Principal components analysis yielded 13 components
      with eigenvalues > 1.0. The Scree test proposed a 6-component solution (39
      items), which explained 59% of the total variation. Internal consistency
      reliabilities computed for the first 6 components (alpha = 0.79-0.95) were
      acceptable. CONCLUSIONS: The final questionnaire, the Diabetes Management
      Evaluation Tool (DMET), was designed to assess patient satisfaction with diabetes
      disease management programs. Although more extensive testing of the questionnaire
      is appropriate, preliminary reliability and validity of the DMET has been
      demonstrated.

PMID- 10895846
TI  - High cardiovascular disease mortality in subjects with visual impairment caused
      by diabetic retinopathy.
AB  - OBJECTIVE: The aim of this study was to assess mortality and causes of death in
      subjects with visual impairment caused by diabetic retinopathy (DR). Only limited
      data are available concerning the mortality of subjects with DR, and to our
      knowledge, no data so far have been published on the mortality of subjects with
      visual impairment caused by DR. RESEARCH DESIGN AND METHODS: We identified 34 men
      and 73 women living in northern Finland with visual impairment caused by DR on 31
      December 1993. The median age of the subjects was 71 years (range 27-88). The
      mortality of these 107 diabetic subjects was followed up for 4 years, until 31
      December 1997, and compared with the mortality rates of 3 age- and sex-matched
      control groups. The first control group consisted of subjects treated for DR by
      laser coagulation from 1990 to 1993. The second control group consisted of
      diabetic subjects who had had fundus photographs taken from 1991 to 1992. The
      third control group comprised nondiabetic subjects selected from the population
      register. Information on deaths was obtained from official death certificates.
      RESULTS: A total of 91 diabetic and 10 nondiabetic subjects died during the
      follow-up. Of the deaths, 51 occurred in the subjects with visual impairment
      caused by DR, with a 4-year mortality rate of 477/1,000 (95% CI 382-571/1,000).
      Mortality rates were 224/1,000 (145-303/1,000) for the diabetic subjects with
      retinopathy treated by laser coagulation; 150/1,000 (82-217/1,000) for the
      diabetic subjects who had undergone fundus photography; and 94/1,000 (46
      165/1,000) for the nondiabetic subjects. Cardiovascular diseases were the
      underlying cause of death in 55% of the subjects with visual impairment.
      Nephropathy was mentioned as the immediate cause of death for only 10% of the
      subjects. Compared with the nondiabetic control subjects, the odds ratios (ORs)
      for all-cause mortality were 5.1 (2.6-11) in the diabetic subjects with visual
      impairment caused by DR, and 5.6 (2.1-19) for mortality caused by diseases of the
      circulatory system. The ORs for all-cause mortality were 2.4 (1.1-5.6) in the
      diabetic subjects with retinopathy treated by laser coagulation and 1.6 (0.68
      4.0) in the diabetic subjects with fundus photographs taken. CONCLUSIONS: The
      survival of diabetic subjects with visual impairment caused by DR was poor. The
      high mortality rate was attributed mainly to cardiovascular diseases. Therefore,
      severe retinopathy proves to be a risk marker of cardiovascular death in diabetic
      patients.

PMID- 10895847
TI  - Impact of diabetes on coronary artery disease in women and men: a meta-analysis
      of prospective studies.
AB  - OBJECTIVE: Women are at a much lower risk of coronary disease mortality than men
      are. It is widely believed that diabetes "erases" this female advantage,
      increasing the risk of heart disease much more in women than in men. In reality,
      the extent of this increased risk is controversial, with studies showing
      conflicting results and wide confidence intervals. Clarification of this issue
      has implications for the pathogenesis of coronary disease, and for public health
      efforts to reduce coronary disease in women. RESEARCH DESIGN AND METHODS: We
      performed a meta-analysis to calculate a summary estimate of the relative risk of
      coronary death among women with diabetes as compared to those without. For
      comparison, we also calculated the analogous risk among men. All prospective
      cohort studies containing both men and women, and both patients with and without
      diabetes, were examined. Sixteen studies were identified; 10 had sufficient data
      for statistical analysis. RESULTS: After combining studies that adjusted for
      other cardiac risk factors, the relative risk of coronary death from diabetes was
      2.58 (95% CI 2.05-3.26) for women and 1.85 (1.47-2.33) for men. This difference
      is statistically significant (P = 0.045). Other sensitivity analyses did not
      change these estimates appreciably. CONCLUSIONS: The impact of diabetes on the
      risk of coronary death is significantly greater for women than men. Further
      research is required to explain this clinically meaningful difference between the
      sexes.

PMID- 10895848
TI  - No major association of breast-feeding, vaccinations, and childhood viral
      diseases with early islet autoimmunity in the German BABYDIAB Study.
AB  - OBJECTIVE: Environmental factors have been suggested to play an important role in
      the pathogenesis of type 1 diabetes. The aim of this study was to assess the
      influence of breast-feeding, vaccinations, and childhood viral diseases on the
      initiation of islet autoimmunity in early childhood. RESEARCH DESIGN AND METHODS:
      Data were prospectively collected from questionnaires obtained at birth, at 9
      months of age, and at 2 years of age in 823 offspring from parents with type 1
      diabetes. By 2 years of age, 31 offspring had islet antibodies, and 10 developed
      overt diabetes by the time of follow-up. RESULTS: In offspring from mothers with
      type 1 diabetes, duration of exclusive and total breast-feeding did not differ
      between islet antibody-positive and -negative children, regardless of HLA
      genotype, and breast-feeding of 3 months or longer was not associated with
      protection from antibody development or diabetes onset. In offspring from
      diabetic fathers, non-statistically significant reductions in exclusive and total
      breast-feeding times were observed in the antibody-positive cohort. Neither type
      nor quantity of vaccinations (including Bacille Calmette-Guerin vaccine;
      haemophilus influenzae vaccine; diphtheria, tetanus, and pertussis vaccine; tick
      born encephalitis vaccine; or measles, mumps, and rubella vaccine) were
      associated with the development of islet antibodies and diabetes. Measles, mumps,
      and rubella were not reported in children with islet antibodies or diabetes.
      CONCLUSIONS: This study showed no evidence that proposed environmental factors
      affect islet antibody development in the first 2 years of life in offspring from
      parents with type 1 diabetes.

PMID- 10895849
TI  - Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients
      with younger age of onset and autoimmune thyroid disease.
AB  - OBJECTIVE: We studied the association between type 1 diabetes with autoimmune
      thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene
      in a Japanese population. RESEARCH DESIGN AND METHODS: We studied 74 Japanese
      type 1 diabetic patients with or without AITD and 107 normal subjects to identify
      the association between CTLA-4 polymorphism and type 1 diabetes using polymerase
      chain reaction-restriction fragment length polymorphism analysis. RESULTS: The
      frequency of the CTLA-4 G allele differed significantly between the type 1
      diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The
      difference in the CTLA-4 G allele became greater between patients with a younger
      age of onset of type 1 diabetes (age at onset <30 years) and the normal control
      subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G
      allele did not differ between type 1 diabetic patients with younger and older age
      of onset (64% vs. 57%). The G allele frequencies in the patients with younger
      onset type 1 diabetes and AITD increased more than in the control patients (P =
      0.025). These differences reflected a significant increase in the frequency of
      G/G genotype--that is, 54% in those with younger-onset type 1 diabetes and AITD,
      39% in those without AITD, and 28% in control subjects. CONCLUSIONS: An
      association was detected between the CTLA-4 gene polymorphism and younger-onset
      type 1 diabetes with AITD. The G variant was suggested to be genetically linked
      to AITD-associated type 1 diabetes of younger onset in this apanese population.
      The defect in these patients presumably lies in a T-cell-mediated autoimmune
      mechanism.

PMID- 10895850
TI  - Repaglinide/troglitazone combination therapy: improved glycemic control in type 2
      diabetes.
AB  - OBJECTIVE: This multicenter open-label clinical trial compared the efficacy and
      safety of repaglinide/troglitazone combination therapy, repaglinide monotherapy,
      and troglitazone monotherapy in type 2 diabetes that had been inadequately
      controlled by sulfonylureas, acarbose, or metformin alone. RESEARCH DESIGN AND
      METHODS: Patients with type 2 diabetes (n = 256) who had inadequate glycemic
      control (HbA1c > or =7.0%) during previous monotherapy were randomly assigned to
      receive repaglinide (0.5-4.0 mg at meals), troglitazone (200-600 mg once daily),
      or a combination of repaglinide (1-4 mg at meals) and troglitazone (200-600 mg
      once daily). After a 4-6 week washout period, the trial assessed 22 weeks of
      treatment: 3 weeks (weeks 0-2) of forced titration, 11 weeks of fixed-dose
      treatment (weeks 3-13), and 8 weeks (weeks 14-21) of titration to maximum dose.
      Changes in HbA1c and fasting plasma glucose (FPG) values were measured. RESULTS:
      The combination therapy showed a significant reduction in mean HbA1c values (
      1.7%) that was greater than with either type of monotherapy Repaglinide
      monotherapy resulted in a reduction of HbA1c values that was significantly
      greater than troglitazone (-0.8 vs. -0.4%) (P < 0.05). Combination therapy was
      more effective in reducing FPG values (-80 mg/dl) than either repaglinide (-43
      mg/dl) or troglitazone (-46 mg/dl) monotherapies. Adverse events were similar in
      all groups. CONCLUSIONS: Combination therapy with repaglinide and troglitazone
      leads to better glycemic control than monotherapy with either agent alone.
      Repaglinide monotherapy was more effective in lowering HbA1c levels than
      troglitazone monotherapy Repaglinide/troglitazone combination therapy was
      effective and did not show unexpected adverse events.

PMID- 10895851
TI  - Differences in the performance of commercially available 10-g monofilaments.
AB  - OBJECTIVE: This independent study was designed to determine the accuracy of 10-g
      monofilaments manufactured and supplied by popular commercial companies. RESEARCH
      DESIGN AND METHODS: A total of 160 new 10-g monofilaments (30 Semmes-Weinstein
      monofilaments [North Coast Medical], 30 Timesco/Sensory Testing Systems
      monofilaments, 50 Owen Mumford Neuropens, and 50 Bailey Instruments
      monofilaments) were tested using a calibrated load cell. Each monofilament was
      subjected to 10 mechanical bucklings of 10 mm while the load cell detected the
      maximum buckling force. Longevity testing was performed on a subset of the
      monofilaments by subjecting them to continuous compressions until the buckling
      force was <9 g. RESULTS: The accuracy of monofilaments to produce a buckling
      force of 10 g varies among manufacturers. Bailey Instruments and Owen Mumford
      filaments were the most accurate with 100% buckling within +/-1.0 g of 10 g. Only
      70% of the Semmes-Weinstein monofilaments from North Coast Medical buckled within
      +/-1.0 g of 10 g. A total of 80% of Timesco filaments buckled at <8 g. Longevity
      tests on Bailey Instruments and Owen Mumford monofilaments demonstrated that 80%
      continued to buckle within 10% of 10 g after 100 compressions, but only 50% were
      within this range after 200 compressions. The maximum amount of recovery achieved
      in any monofilament occurred within 24 h. CONCLUSIONS: Monofilaments made by
      either Bailey Instruments or Owen Mumford are recommended for use in clinical
      practice. North Coast Medical monofilaments may operate differently in the U.S.
      because of different environmental conditions such as differences in humidity.
      Timesco/Sensory Testing Systems monofilaments were neither accurate enough nor
      Conformity European marked to recommend their use in the U.K. Longevity and
      recovery testing suggest that each monofilament will survive usage on
      approximately 10 patients before needing a recovery time of 24 h before further
      use.

PMID- 10895852
TI  - Autonomic dysfunction and urinary albumin excretion rate are associated with an
      abnormal blood pressure pattern in normotensive normoalbuminuric type 1 diabetic
      patients.
AB  - OBJECTIVE: To analyze the role of autonomic function and other possible factors
      associated with a blunted fall in nocturnal blood pressure. RESEARCH DESIGN AND
      METHODS: A total of 39 normotensive normnoalbuminuric type 1 diabetic patients
      were studied. Glomerular filtration rate (51Cr-EDTA technique), extracellular
      volume (51Cr-EDTA distribution volume), and urinary albumin excretion rate (UAER)
      (by radioimmunoassay) were measured. The subjects' 24-h ambulatory blood pressure
      and a 24-h electrocardiogram were recorded simultaneously Heart rate variability
      was calculated in the time domain for 24 h, in the frequency domain at night, at
      rest in the supine position, and during tilt. Patients were classified according
      to diastolic blood pressure (dBP) night/day ratio as dipper patients (< or =0.9)
      and nondipper patients (>0.9). RESULTS: Nondipper patients presented a higher low
      frequency (LF) component (a sympathetic index) and higher LF/high-frequency (HF)
      ratio during sleep than dipper patients (0.29 +/- 0.12 vs. 0.19 +/- 0.10
      normalized units [n.u.], P = 0.008; and 0.98 +/- 0.53 vs. 0.55 +/- 0.45 n.u., P =
      0.007, respectively). At rest, the LF component in nondipper patients (0.38 +/-
      0.13 n.u.) was higher than in dipper patients (0.27 +/- 0.12 n.u., P = 0.04).
      After the tilt, nondipper patients did not show an increase in the LF component
      (P = 0.32), but in dipper patients, the increase was significant (P = 0.001). In
      both groups, tilting promoted a decrease in the HF component (a parasympathetic
      index). In a stepwise multiple linear regression analysis, the LF component
      during sleep and the UAER accounted for 24% of the variability in the dBP
      night/day ratio. CONCLUSIONS: The predominance of sympathetic activity and
      increased levels of UAER, although within the normal range, are associated with a
      blunted fall in nocturnal dBP in normoalbuminuric normotensive type 1 diabetic
      patients.

PMID- 10895853
TI  - Transmembrane electron transfer in diabetic nephropathy.
AB  - OBJECTIVE: Erythrocytes (red blood cells [RBCs]) reduce extracellular
      ferricyanide by transmembrane transfer of reducing equivalents involving
      ascorbate recycling. RESEARCH DESIGN AND METHODS: Because ascorbate regeneration
      is glutathione (GSH) dependent and cells may be depleted of GSH in diabetes, we
      measured RBC GSH, plasma sulfhydryl (SH) groups, and RBC-mediated ferricyanide
      reduction in 30 type 1 diabetic patients (age 34 +/- 10 years, disease duration
      20 +/- 8 years; no complications, n = 10; retinopathy, n = 10; nephropathy, n =
      10), their 36 siblings (age 39 +/- 13 years), and matched healthy volunteers.
      RESULTS: Fasting plasma glucose was 15 +/- 7 mmol/l (vs. 5 +/- 1 in control
      subjects, P < 0.001), HbA1c 8.4 +/- 1.5% (vs. 5.4 +/- 0.3, P < 0.001), GSH 0.76
      +/- 0.12 mg/ml packed RBCs (vs. 0.88 +/- 0.18, P < 0.01), SH groups 401 +/- 72
      micromol/l (vs. 444 +/- 56, P < 0.05), and ferrocyanide generation 15 +/- 5
      micromol/ml RBC per h (vs. 13 +/- 5, NS). In comparison with 10 normoalbuminuric
      diabetic subjects with retinopathy, 10 patients with diabetic nephropathy had
      similar fasting plasma glucose, HbA1c, and SH groups; lower RBC GSH (0.73 +/-
      0.08 vs. 0.85 +/- 0.11, P < 0.05); and higher ferrocyanide generation (18 +/- 4
      vs. 14 +/- 5, P < 0.05). The 10 patients without complications differed from the
      10 healthy volunteers in glycemic control and RBC GSH. RBC electron transfer
      correlated with plasma lactate (r = 0.8, P = 0.01) only in the uncomplicated
      group. No difference was detected between siblings and healthy control subjects
      or between siblings of subjects in the nephropathy and retinopathy groups. Among
      diabetic patients, the rate of ferrocyanide generation was associated with
      urinary albumin excretion, plasma creatinine, and SH groups (multiple r = 0.6, P
      < 0.01). CONCLUSIONS: Transmembrane electron transfer is selectively increased in
      diabetic nephropathy, where RBC GSH is also depleted. The abnormality is peculiar
      to the nephropathy group and not contributed by familial or hereditary components
      because the electron flow was normal in siblings. The close relationship between
      cytosolic NADH and RBC electron transfer observed in diabetic patients without
      complications seems to be lost in the microangiopathic patients. Whereas patients
      with retinopathy alone still had normal activity of the RBC-reducing system,
      patients with nephropathy showed significantly increased activity, unrelated to
      metabolic parameters or plasma lactate concentration and correlated with renal
      function parameters and plasma thiols.

PMID- 10895854
TI  - Effect of pinitol treatment on insulin action in subjects with insulin
      resistance.
AB  - OBJECTIVE: Endogenous low-molecular-weight glycans containing pinitol (3-O-methyl
      D-chiro-inositol) and D-chiro-inositol are thought to mediate certain actions of
      insulin. We tested the hypothesis that oral administration of soybean-derived
      pinitol would improve insulin sensitivity in obese subjects (BMI = 36.6 kg/m2)
      with diet-treated type 2 diabetes or glucose intolerance (HbA1c = 6.8%). RESEARCH
      DESIGN AND METHODS: There were 22 subjects randomized to receive either pinitol
      20 mg x kg(-1) x day(-1) (n = 12) or placebo (n = 10) in a 28-day double-blinded
      trial. RESULTS: No toxicity due to the pinitol was observed during the study The
      sensitivity of glucose and lipid metabolism to insulin were assessed by
      measurement of whole-body glucose, palmitate, and glycerol kinetics during basal
      conditions and a hyperinsulinemic-euglycemic clamp. Metabolic measurements were
      made at baseline and again at the end of the study Final plasma levels of pinitol
      were 48-fold (1.06 +/- 0.15 vs. 0.02 +/- 0.01 micromol/l, P < 0.0001) and D-chiro
      inositol levels 14-fold (0.56 +/- 0.08 vs. 0.04 +/- 0.02 micromol/l, P < 0.0001)
      greater in the pinitol group compared with placebo. CONCLUSIONS: Four weeks of
      pinitol treatment did not alter baseline glucose production, insulin-mediated
      glucose disposal, or rates of appearance of free fatty acids and glycerol in
      plasma. We conclude that plasma levels of both pinitol and D-chiro-inositol are
      very responsive to pinitol ingestion, but insulin sensitivity does not increase
      after pinitol treatment in individuals with obesity and mild type 2 diabetes.

PMID- 10895856
TI  - European Association for the Study of Diabetes Annual Meeting, 1999: treatment
      modalities.

PMID- 10895855
TI  - Lipoprotein concentrations and carotid atherosclerosis by diabetes status:
      results from the Insulin Resistance Atherosclerosis Study.
AB  - OBJECTIVE: Lipoprotein concentrations are associated with the development of
      atherosclerosis in people with and without diabetes. The relative strength of
      these associations could differ by diabetes status as a result of diabetes
      related lipoprotein modifications. RESEARCH DESIGN AND METHODS: The associations
      between lipoprotein concentrations and internal and common carotid artery intimal
      medial thickness (IMT) assessed by B-mode ultrasonography were examined by
      diabetes status in a cross-sectional analysis among 1,391 participants in the
      Insulin Resistance Atherosclerosis Study. Participants included 442 individuals
      with type 2 diabetes, 308 with impaired glucose tolerance, and 641 with normal
      glucose tolerance. RESULTS: The differences in internal and common carotid IMT
      between the highest and lowest tertiles of LDL were 58.1 microm (P = 0.054) and
      51.0 microm (P < 0.001), respectively. The differences in internal and common
      carotid IMT between the lowest and highest tertiles of HDL were 56.2 microm (P =
      0.07) and 37.8 microm (P = 0.003), respectively Triglycerides and VLDL were not
      associated with IMT. These associations did not differ significantly because of
      diabetes status. CONCLUSIONS: These results support the importance of
      dyslipidemia as a major risk factor for atherosclerosis in people with diabetes.
      Future research in humans should measure lipoprotein oxidizability, glycation,
      size, and composition directly in people of differing glucose tolerance status to
      address the importance of diabetes-related lipoprotein modifications more
      conclusively.

PMID- 10895857
TI  - Ketosis-onset diabetes without islet-associated autoantibodies in a patient with
      MELAS.

PMID- 10895859
TI  - Coxsackie B virus-induced autoimmunity to GAD does not lead to type 1 diabetes.

PMID- 10895858
TI  - Stability of disease-associated antibody titers in pregnant women with type 1
      diabetes with or without residual beta-cell function.

PMID- 10895860
TI  - Does the choice of treatment for type 2 diabetes affect the physiological
      response to hypoglycemia?

PMID- 10895862
TI  - Hyperinsulinemia and central adiposity: influence of chronic insulin therapy in
      type 1 diabetes.

PMID- 10895861
TI  - Hypoglycemia and pulmonary edema: a forgotten association.

PMID- 10895863
TI  - High total serum renin concentrations are associated with the development of
      background retinopathy in adolescents with type 1 diabetes.

PMID- 10895865
TI  - Risk for silent celiac disease is higher in diabetic children with a diabetic
      sibling than in sporadic cases.

PMID- 10895864
TI  - Plasma homocysteine and its determinants in diabetic retinopathy.

PMID- 10895866
TI  - Laboratory testing for microalbuminuria in the general community.

PMID- 10895867
TI  - Elevated plasma levels of proinsulin in adult patients with Down's syndrome.

PMID- 10895869
TI  - Castration and diabetes.

PMID- 10895868
TI  - Angiotensin II blockade is associated with decreased plasma leukocyte adhesion
      molecule levels in diabetic nephropathy.

PMID- 10895870
TI  - Decompensation of leucine nitrogen kinetics in gestational diabetes mellitus.

PMID- 10895871
TI  - Response to Glasgow and Anderson. Compliance and adherence.

PMID- 10895872
TI  - Increased plasma plasminogen activator inhibitor 1 in relatives of type 2
      diabetic patients.

PMID- 10895873
TI  - Homeostasis model assessment and related simplified evaluations of insulin
      sensitivity from fasting insulin and glucose.

PMID- 10895874
TI  - Assessment of insulin sensitivity: comparison between simplified evaluations and
      minimal model analysis.

PMID- 10895875
TI  - Lack of evidence for bromocriptine effect on glucose tolerance, insulin
      resistance, and body fat stores in obese type 2 diabetic patients.

PMID- 10895876
TI  - Are the results really different?

PMID- 10895877
TI  - Homocysteine and insulin levels in type 2 diabetic patients.

PMID- 10895878
TI  - Comparison between 2 insulin sensitivity indexes in obese patients.

PMID- 10895879
TI  - Type 1 diabetes in sardinia is not linked to nitrate levels in drinking water.

PMID- 10895880
TI  - Puberty as a risk factor for diabetic neuropathy.

PMID- 10895881
TI  - No relationship between antibodies to GAD and microangiopathic complications in
      young Chinese diabetic patients.

PMID- 10895882
TI  - Changes in neuronal activities in the two ventral posterior medial thalamic
      nuclei in an experimental model of trigeminal pain in the rat by constriction of
      one infraorbital nerve.
AB  - The present study analyzes the activity of 120 neurons recorded in the two ventro
      postero-medial (VPM) nuclei of the thalamus in a rat model of trigeminal
      neuropathic pain. Twenty-eight rats were tested 2 weeks after a chronic
      constriction injury (CCI) of the infraorbital nerve (IoN). These animals
      exhibited violent pain-related reactions to extremely weak mechanical stimuli
      applied to the lesioned and, to a lesser extent, unlesioned IoN territories. The
      activities of neurons recorded in the VPMc (n = 80) and VPMi (n = 40),
      contralateral and ipsilateral to the injured nerve, respectively, were compared
      with those of 62 neurons recorded in the VPM of ten normal rats (VPMn). The
      neuronal background activity was higher in the VPM of CCI-IoN rats than in normal
      rats (about 4 vs 1 spike/s). The proportion of neurons which were driven by
      mechanical stimulations applied contralaterally to their recording site, was
      comparable in the three VPM (63-70%), but the effective stimulus modality
      differed significantly between the normal and the lesioned rats. In particular,
      the number of neurons driven by vibrissa or guard hair movements dramatically
      decreased in the VPM of CCI-IoN rats, mainly in the VPMc (67% of neurons with a
      receptive field (RF) in the VPMn vs 12% in the VPMc). Inversely, a consistent
      number of neurons in both the VPMc and VPMi were driven by other stimulus
      modalities applied to the IoN territory (moderate pressure for VPMc neurons,
      pinch or pinprick for both VPMc and VPMi neurons). The responses so induced were
      especially intense and included afterdischarges. In contrast to the VPMn neurons,
      the RFs of both the VPMc and VPMi neurons included two vibrissae at least, and
      were occasionally discontinuous and multimodal, including both vibrissae and
      cutaneous areas for VPMc units. The bilateral changes in VPM responsiveness and
      in behavior suggest the involvement of central processing of sensory information,
      which are set off by the CCI-IoN. The putative mechanisms and functional
      implication of the changes in the VPM neuronal activities are discussed.

PMID- 10895883
TI  - Hierarchy within human SI: supporting data from cytochrome oxidase,
      acetylcholinesterase and NADPH-diaphorase staining patterns.
AB  - The human primary somatosensory cortex consists of four cytoarchitectonic
      subdivisions (3a, 3b, 1 and 2) that are likely to contain distinct somatosensory
      representations. The intraareal organization of these areas as well as that of
      the primary motor cortex (area 4) has been analyzed using histochemical stains of
      cytochrome oxidase, acetylcholinesterase and NADPH-diaphorase activity in normal
      human brains. Cytochrome oxidase activity was revealed in individual cortical
      neurons and neuropil. Areas 4, 3a and 3b were on average darker than areas 1 and
      2. The laminar distribution of cytochrome oxidase activity varied in different
      areas. A prominent dark band was present in layers IV and lower III in areas 3a
      and 3b and in layer III in areas 1, 2 and 4. Acetylcholinesterase staining
      revealed fibers and pyramidal cells in layers III and V; stained layer III
      pyramids were rare in areas 3a and 3b and numerous in areas 1, 2 and 4. NADPH
      diaphorase positive elements included Golgi-like stained non-pyramidal neurons
      and Nissl-like stained pyramidal neurons; the former were found, in small
      numbers, in layer II of areas 4, 3a, 3b and 1, and the latter in layers III and V
      of areas 4 and 3a and in layer V of areas 1 and 2. The dark cytochrome oxidase
      staining of layer IV and the paucity of acetylcholinesterase positive pyramids in
      areas 3a and 3b resemble the pattern found in primary visual and auditory areas,
      whereas the dark cytochrome oxidase staining in layer III and abundance of
      acetylcholinesterase positive pyramids in areas 1 and 2 that of association
      areas. These results suggest that the four areas included in human SI constitute
      hierarchical stages of cortical processing, with 3a and 3b corresponding to
      primary and 1 and 2 to secondary areas.

PMID- 10895884
TI  - Attention-related, cross-modality modulation of somatosensory neurons in primate
      ventrobasal (VB) thalamus.
AB  - Attention-related modulation (AM) of the somatosensory responses of single
      neurons has been demonstrated in the cerebral cortex and medullary dorsal horn,
      but not in the ventrobasal thalamus. The somatically evoked activity was recorded
      of single units in the ventral posterior lateral thalamus (VPL) of awake monkeys
      while they detected the termination of task-relevant somatic or visual stimuli.
      Eighteen of 56 somatically responsive VPL neurons are reported that were recorded
      for enough time for a complete analysis of their responses during both the visual
      and somatic attention tasks. All neurons were spontaneously active and responded
      either to innocuous cutaneous (13/18) or deep (5/18) stimuli. Seven neurons
      (7/18, 38.8%) showed AM of somatosensory responsiveness. Two cells (2/7, 28.6%)
      showed AM only during the visual task, two others (2/7, 28.6%) only during the
      somatosensory task, and three cells (3/7, 42.8%) showed AM during both tasks. All
      five cells showing AM during the somatosensory task had enhanced responses to the
      task-relevant somatic stimulus. In contrast, the somatosensory responses of all
      five cells showing AM during the visual task were reduced. It is concluded that
      selective attention is associated with a modality specific modulation of the
      somatosensory responses of a sub-population of neurons within the primate VPL
      nucleus.

PMID- 10895885
TI  - Effects on discrimination performance of selective attention to tactile features.
AB  - This study examined selective attention to tactile dimensions by combining a
      selective cueing paradigm with a test of integrality. In Experiment 1, subjects
      selectively attended to changes in the frequency or duration of pairs of
      vibrotactile stimuli and identified the higher frequency or longer duration
      stimulus. In Experiment 2, using surface gratings in an identical experimental
      procedure, subjects identified the rougher or longer duration stimulus. In both
      experiments, greater performance accuracy was found on trials where the cue
      correctly (valid) predicted the changing dimension, vs incorrectly (invalid) cued
      or no-cue (neutral) trials. More errors on the invalidly vs neutrally cued trials
      show the cost of focal attention. Increases in performance on validly vs
      neutrally cued trials show a benefit of filtering irrelevant stimuli in the cued
      conditions. Results effectively demonstrate focal attention to tactile features.
      Tests of integrality, in terms of the effects of correlated change in both
      dimensions, showed no redundancy gain for either vibrotactile or grating tasks,
      suggesting that frequency and roughness are separable from stimulus duration.
      Interference of negative correlated change for frequency but not roughness
      discriminations may be explained by differences in task difficulty.

PMID- 10895886
TI  - Immunocytochemical identification of proteins within the Pacinian corpuscle.
AB  - Light- and electron-microscopic immunocytochemistry (ICC) was performed on
      Pacinian corpuscles (PCs) obtained from cat mesentery to determine the presence
      and location of various proteins within the accessory capsule and the neurite.
      Antibodies to tubulin, neurofilament 200, actin, collagen II and V, glial
      fibrillary acidic protein (GFAP) and S-100 were used. Type II collagen was
      localized only in the outer core of the accessory capsule, which is composed of
      an inner core, an intermediate layer or growth zone, an outer core and an
      external capsule. Type V collagen was found only in the intermediate growth zone.
      Intermediate filaments labeled with anti-GFAP were only found in the inner core.
      The calcium-binding protein that was labeled by anti-S-100 was found only in the
      inner core. Diffuse and variable staining for actin is present throughout the
      accessory capsule. The differences in distribution of these various proteins
      within the capsule suggest different structural/functional properties of the
      various capsule regions. The neurite was found to contain microtubules (i.e.,
      tubulin) and neurofilaments throughout, but these cellular inclusions were not
      found within the cytoplasmic extensions (filopodia) that project from the neurite
      into the hemilamellar clefts formed by the inner-core hemilamellae. The
      extensions, however, were found to contain actin in a much greater density than
      that seen in the neurite proper. The presence of actin, but apparent lack of
      other cytostructural elements within the extensions, is highly reminiscent of the
      composition of stereocilia found on vestibular and auditory hair cells. Since
      stereocilia have been shown to play a role in hair-cell mechanotransduction, it
      is possible that the cytoplasmic extensions are significantly involved with
      mechanotransduction within the PC.

PMID- 10895887
TI  - Coding of deflection velocity and amplitude by whisker primary afferent neurons:
      implications for higher level processing.
AB  - Within the rat whisker-to-barrel pathway, local circuits in cortical layer IV are
      more sensitive to the initial timing of deflection-evoked thalamic responses than
      to the total number of spikes comprising them. Because thalamic response timing
      better reflects whisker deflection velocity than amplitude, cortical neurons are
      more responsive to the former than the latter. The aim of this study is to
      determine how deflection velocity and amplitude may be encoded by the primary
      afferent neurons innervating the vibrissae. Responses of 81 extracellularly
      recorded trigeminal ganglion neurons (60 slowly and 21 rapidly adapting) were
      studied using controlled whisker stimuli identical to those used previously to
      investigate the velocity and amplitude sensitivities of thalamic and cortical
      neurons. For either slowly (SA) or rapidly adapting (RA) neurons, velocity is
      reflected by both response magnitude, measured as the total number of evoked
      spikes/stimulus, and initial firing rate, measured as the number of spikes
      discharged during the first 2 ms of the response. Deflection amplitude, on the
      other hand, is represented only by the SA population in their response
      magnitudes. Thus, in both populations initial firing rates unambiguously reflect
      deflection velocity. Together with previous findings, results demonstrate that
      information about deflection velocity is preserved throughout the whisker-to
      barrel pathway by central circuits sensitive to initial response timing.

PMID- 10895888
TI  - Dual task-related changes in the synchronous activity of wrist extensor type
      identified motor units in humans.
AB  - The coupling between the firings of 33 pairs of motor units tested in the
      extensor carpi radialis muscles was evaluated by cross-correlation analysis and
      compared during isometric wrist extension and hand clenching. A slightly greater
      amount of synchrony was observed during hand clenching (0.042 +/- 0.024 vs 0.035
      +/- 0.017 synchronous impulses per trigger). This trend did not reach however the
      level of significance and the changes were actually found to be heterogeneous: in
      15 out of the 33 pairs tested, synchronous activity with a narrow coupling (4.6
      +/- 2.4 ms) consistent with short-term synchrony was greater during hand
      clenching whereas in nine other pairs, synchronous activity with a broader
      dispersion (9.0 +/- 4.5 ms) was reduced. These opposite changes could not be
      explained in terms of changes in the firing pattern of the motor units and were
      found instead to correlate with the motor units' biomechanical properties. Motor
      units with high recruitment thresholds and fast rising twitches showed
      predominantly an increase in synchrony; whereas the motor unit pairs with low
      recruitment thresholds and slow twitches showed either an increase or a decrease.
      The enhanced short-term synchrony suggests that common inputs distributed to
      motoneurones of all types were more effective during hand clenching whereas the
      decrease in weakly coupled synchronous activity suggests that other inputs
      synchronized at a pre-synaptic level and distributed more specifically to motor
      units recruited at low force levels were less effective. The possible origins of
      the inputs reflected in the dual changes are discussed in terms of the supra
      spinal and peripheral pathways controlling the wrist extensor motoneurones during
      wrist extension and hand clenching.

PMID- 10895889
TI  - The effects of stimulus location on the gating of touch by heat- and cold-induced
      pain.
AB  - The influence of heat- and cold-induced pain on tactile sensitivity, a "touch
      gate", was measured under conditions in which the location of the noxious stimuli
      was varied with respect to the tactile stimulus applied to the thenar eminence of
      humans. Vibrotactile thresholds were measured in the absence of pain and during
      administration of a painful stimulus, with the stimulus frequencies selected to
      activate independently the four psychophysical channels hypothesized to exist in
      human glabrous skin. Heat-induced pain produced by spatially co-localizing the
      noxious stimuli with the tactile stimuli was found, on average, to elevate
      threshold amplitude by 2.2 times (6.7 dB). Co-localized, cold-induced pain raised
      the average thresholds by about 1.5 times (3.6 dB). Heat-induced pain presented
      contralaterally produced no change in vibrotactile sensitivity indicating that
      the effect is probably not due to attentional mechanisms. Ipsilateral heat
      induced pain caused an elevation in tactile thresholds even when the noxious and
      non-noxious stimuli were not co-localized, and the effect may seem to require
      that the painful stimulus be within the somatosensory region defined possibly in
      terms of dermatomal organization. Thus the effect is probably related to
      somatotopic organization and is not peripherally mediated. A brief discussion as
      to the possible locus of the touch gate within the nervous system is also given.

PMID- 10895890
TI  - Questions duration of treatment with phenylbutazone.

PMID- 10895891
TI  - Cardiac output measured by lithium dilution, thermodilution, and transesophageal
      Doppler echocardiography in anesthetized horses.
AB  - OBJECTIVE: To assess the suitability of lithium dilution as a method for
      measuring cardiac output in anesthetized horses, compared with thermodilution and
      transesophageal Doppler echocardiography. ANIMALS: 6 horses (3 Thoroughbreds, 3
      crossbreeds). PROCEDURE: Cardiac output was measured in 6 anesthetized horses as
      lithium dilution cardiac output (LiDCO), thermodilution cardiac output (TDCO),
      and transesophageal Doppler echocardiographic cardiac output (DopplerCO). For the
      LiDCO measurements, lithium chloride was administered i.v., and cardiac output
      was derived from the arterial lithium dilution curve. Sodium nitroprusside,
      phenylephrine hydrochloride, and dobutamine hydrochloride were used to alter
      cardiac output. Experiments were divided into 4 periods. During each period, 3
      LiDCO measurements, 3 DopplerCO measurements, and 3 sets of 3 TDCO measurements
      were obtained. RESULTS: 70 comparisons were made between LiDCO, DopplerCO, and
      triplicate TDCO measurements over a range of 10 to 43 L/min. The mean (+/- SD) of
      the differences of LiDCO - TDCO was -0.86 +/- 2.80 L/min; LiDCO = -1.90 + 1.05
      TDCO (r = 0.94). The mean of the differences of DopplerCO - TDCO was 1.82 +/-
      2.67 L/min; DopplerCO = 2.36 + 0.98 TDCO (r = 0.94). The mean of the differences
      of LiDCO - DopplerCO was -2.68 +/- 3.01 L/min; LiDCO = -2.53 + 0.99 DopplerCO (r
      = 0.93). CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that lithium
      dilution is a suitable method for measuring cardiac output in horses. As well as
      being accurate, it avoids the need for pulmonary artery catheterization and is
      quick and safe to use. Monitoring cardiac output during anesthesia in horses may
      help reduce the high anesthetic mortality in this species.

PMID- 10895892
TI  - Passive transfer of colostral immunoglobulin G in neonatal llamas and alpacas.
AB  - OBJECTIVE: To evaluate precolostral hypogammaglobulinemia in neonatal llamas and
      alpacas, to determine when postcolostral peak serum IgG concentrations develop,
      to determine whether differences in postcolostral serum IgG concentrations
      between llamas and alpacas exist, and to determine postcolostral half-life of
      serum IgG in llamas and alpacas. DESIGN: Prospective observational study.
      ANIMALS: 29 llama and 10 alpaca crias. PROCEDURE: Blood samples were collected
      prior to suckling and on days 1, 2, and 3 after parturition and analyzed for
      serum IgG concentration by use of a commercial radial immunodiffusion assay.
      Additional samples were collected on days 8, 13, and 18 from 8 crias to determine
      mean half-life of IgG. RESULTS: Llamas and alpacas are born severely
      hypogammaglobulinemic. Mean serum IgG concentrations for day-1, -2, and -3
      samples for llamas were 1,578 mg/dl, 1,579 mg/dl, and 1,401 mg/dl, respectively,
      and for alpacas were 2,024 mg/dl, 1,806 mg/dl, and 1,669 mg/dl, respectively.
      Peak serum immunoglobulin concentration developed between days 1 and 2. Mean half
      life of IgG for all crias was 15.7 days. CONCLUSIONS AND CLINICAL RELEVANCE:
      Although increased mortality has been linked to failure of passive transfer, it
      is clearly possible to raise crias that have low serum immunoglobulin
      concentrations. Llamas and alpacas do not differ significantly with respect to
      immunoglobulin absorption or IgG concentration in neonates. The optimal sampling
      time for passive transfer status is between 1 and 2 days.

PMID- 10895893
TI  - Evaluation of the measurement of leukotriene B4 concentrations in exhaled
      condensate as a noninvasive method for assessing mediators of inflammation in the
      lungs of calves.
AB  - OBJECTIVE: To determine whether measurement of an inflammatory mediator in
      exhaled condensate could provide a noninvasive method for evaluating lungs of
      calves. ANIMALS: 84 calves < or = 2 months old. PROCEDURE: Concentration of
      leukotriene B4 (LTB4) was evaluated in the exhaled condensate of healthy calves
      and calves with experimentally induced respiratory tract infections. For
      collection of samples of exhaled condensate, the total amount of exhaled air was
      directed into a cooled double-jacketed tube. Each tube was sealed and stored at 
      80 C. The LTB4 concentration was measured, using an ELISA. RESULTS: In exhaled
      condensates of clinically healthy calves, normally distributed and highly
      reproducible LTB4 concentrations (mean +/- SD, 116.1 +/- 55.4 pg/ml) were
      measured. After experimentally induced infection with Pasteurella multocida
      serovar D, LTB4 in exhaled condensate increased significantly (mean, 179%
      increase), compared with basal concentrations before infection; this increase in
      LTB4 was significantly correlated with deterioration in lung function. In 2 of 4
      calves experimentally infected with bovine respiratory syncytial virus, the LTB4
      concentration in exhaled condensate increased (300 to 400% increase), compared
      with baseline values, which was associated with development of bronchial
      hyperresponsiveness after infection. CONCLUSIONS AND CLINICAL RELEVANCE:
      Collection of exhaled condensate is tolerated well by calves and is an acceptable
      method for obtaining fluid from exhaled air originating from the lungs. This
      method provides alternatives for diagnosing and evaluating treatment of naturally
      acquired and experimentally induced diseases of the lungs and airways in calves.

PMID- 10895894
TI  - Reference values for activated coagulation time in cats.
AB  - OBJECTIVE: To establish reference values for activated coagulation time (ACT) in
      cats by use of jugular venipuncture and direct collection of blood into ACT
      vacuum tubes. ANIMALS: 100 clinically normal cats that were to have elective
      surgery performed at a private practice. PROCEDURE: Collection of 3 blood samples
      for ACT measurement was attempted for each cat at the time of elective surgery:
      sample 1, obtained before sedation; sample 2, tube 1 of 2 consecutive samples
      obtained from a single venipuncture of the contralateral jugular vein after
      sedation with acepromazine and ketamine hydrochloride; and sample 3, tube 2
      collected immediately following collection of sample 2 without removing the
      needle from the vein. Venipuncture quality was rated subjectively on a 3-point
      scale. RESULTS: Median ACT were 95 seconds for each sample group. The middle 95%
      of values ranged inclusively from 55 to 185 seconds (sample 1), 65 to 135 seconds
      (sample 2), 45 to 145 seconds (sample 3), and 55 to 165 seconds overall (samples
      1, 2, and 3). Significant differences in ACT values were not detected between
      sample groups. Significant relationships between ACT and venipuncture quality or
      sex of cat were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: With the ACT
      protocols used, clinically normal cats had ACT of < 165 seconds. The ACT in cats
      does not appear to be significantly affected by sex, sedation with acepromazine
      and ketamine, or by moderately traumatic venipunctures. These results refute
      widespread statements that ACT should be < 65 seconds in healthy cats. Cats with
      ACT repeatedly > 165 seconds should be further evaluated for hemostatic
      disorders.

PMID- 10895895
TI  - Cytokine secretion by peripheral blood mononuclear cells from cows infected with
      Mycobacterium paratuberculosis.
AB  - OBJECTIVE: To compare cytokine secretion patterns of peripheral blood mononuclear
      cells (PBMC) from healthy cows and cows subclinically and clinically infected
      with Mycobacterium paratuberculosis. ANIMALS: 5 noninfected cows, 6 cows with
      subclinical paratuberculosis, and 4 cows with clinical paratuberculosis.
      PROCEDURE: PBMC were isolated, and concentrations or activities of secreted
      interleukin (IL)-1, IL-2, IL-6, tumor necrosis factor (TNF), and interferon-gamma
      (IFN-gamma) were measured after in vitro stimulation of cells with concanavalin A
      (ConA), lipopolysaccharide (LPS), or a whole-cell sonicate of M paratuberculosis
      (MpS). Proliferative responses of PBMC were also determined after stimulation
      with ConA, phytohemagglutinin, pokeweed mitogen (PWM), or MpS. RESULTS: After
      stimulation with ConA, cells from subclinically infected cows secreted
      significantly more, and cells from clinically infected cows secreted
      significantly less, IFN-gamma, compared with cells from control cows. Cells from
      cows with subclinical paratuberculosis produced significantly more TNF and IFN
      gamma in response to MpS than cells from the other 2 groups. Stimulation of PBMC
      from subclinically infected cows with ConA or MpS resulted in significantly
      higher proliferative responses, compared with cells from control and clinically
      infected cows. In contrast, clinically infected cows had significantly higher
      proliferative responses to PWM than cells from the other 2 groups. CONCLUSIONS
      AND CLINICAL RELEVANCE: A decrease in T-cell responses to mitogens or MpS was
      observed in cows clinically infected with M paratuberculosis, compared with
      subclinically infected cows, suggesting that activated T cells may delay the
      progression of paratuberculosis.

PMID- 10895896
TI  - Pharmacokinetics and pharmacodynamics of terbutaline in healthy horses.
AB  - OBJECTIVE: To determine pharmacokinetics of terbutaline in healthy horses and to
      relate serum terbutaline concentrations with the drug's pharmacodynamic effects.
      ANIMALS: 6 healthy horses. PROCEDURE: Horses were given terbutaline i.v. (10
      microg/kg of body weight) and, 1 week later, p.o. (100 microg/kg). Responses to
      drug administration (eg, heart rate and serum lactate concentration) were
      measured. Serum terbutaline concentration was measured by means of gas
      chromatography with mass spectrometry. Protein binding was determined in vitro.
      RESULTS: Following i.v. administration, median maximum serum terbutaline
      concentration and mean residence time were 9.3 ng/ml and 30 minutes,
      respectively. Bioavailability following oral administration was < 1%. All horses
      developed sweating, trembling, excitement, and tachycardia during i.v. infusion.
      The 2 horses with the highest serum terbutaline concentrations developed severe
      tachycardia and CNS stimulation; 30 minutes after the i.v. infusion was
      completed, they were hyperventilating and lethargic. Heart rate and serum lactate
      concentration increased as serum terbutaline concentration increased. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results indicated that terbutaline is rapidly cleared
      from the bloodstream following i.v. administration to horses, suggesting that
      continuous i.v. infusion would be needed to maintain therapeutic serum
      concentrations. Oral administration of terbutaline to horses is not practical
      because of the low bioavailability.

PMID- 10895897
TI  - Effects of human recombinant interleukin-1beta on canine articular chondrocytes
      in three-dimensional culture.
AB  - OBJECTIVE: To determine the effects of interleukin (IL)-1beta on matrix synthesis
      and degradation by chondrocytes cultured in a 3-dimensional (3-D) gel medium.
      SAMPLE POPULATION: Chondrocytes from 7 dogs. PROCEDURE: Articular chondrocytes
      were harvested and cultured in 3-D gel medium alone or with 10 or 20 ng IL
      1beta/ml that was added beginning on day 0, 3, 6, or 9. On days 3, 6, 12, and 20
      of 3-D culture, samples of the liquid medium were evaluated for glycosaminoglycan
      (GAG), prostaglandin E2 (PGE2), and matrix metalloprotease (MMP)-3 content. The 3
      D plug in each well was evaluated for histologic characteristics of viability,
      cell morphology, and proteoglycan staining, immunohistochemically stained for
      collagen type II, and spectrophotometrically analyzed for GAG content. RESULTS:
      Significant differences for all variables were detected between controls and each
      IL-1beta group, among groups with different IL-1beta concentrations, and among
      groups with IL-1beta added at various time points. Chondrocytes exposed to IL
      1beta had loss of GAG, increased PGE2 and MMP-3 concentrations, and lack of
      collagen type-II synthesis. These IL-1beta effects appeared to be time and
      concentration dependent. CONCLUSIONS: Addition of IL-1beta to chondrocytes in 3-D
      gel medium results in time- and concentration-dependent effects on matrix
      synthesis and degradation and provides an appropriate in vitro model for many of
      the pathophysiologic events associated with osteoarthritis.

PMID- 10895898
TI  - Hematologic, plasma protein, and biochemical profiles of brown pelicans
      (Pelecanus occidentalis).
AB  - OBJECTIVE: To establish hematologic and biochemical reference values for the
      brown pelican (Pelecanus occidentalis). ANIMALS: 31 captive, healthy, but
      permanently disabled pelicans and 35 wild-caught, healthy pelicans from a
      rehabilitation facility on the east coast of Florida. PROCEDURES: Samples of
      venous blood were collected from each pelican, and hematologic, plasma
      biochemical, and electrophoretic protein analyses were performed. Student t-tests
      were used to compare blood values between captive versus wild-caught, adult male
      versus adult female, and adult versus juvenile pelicans. RESULTS: Hematologic and
      electrophoretic values were similar between male and female, adult and juvenile,
      and captive and wild-caught pelicans. Significant sex differences existed for
      plasma calcium and triglyceride concentrations. Plasma concentrations of calcium,
      cholesterol, and CO2 content differed between captive and wild-caught adults. No
      significant differences were found between wild-caught adult and juvenile
      pelicans. CONCLUSIONS AND CLINICAL RELEVANCE: Our plasma biochemical results are
      similar to those of other brown pelicans and confamilial species. Additional
      studies on seabirds are encouraged, as age, sex, reproductive status, feeding
      habits, and captivity are important variables for health assessment in this and
      other aquatic species.

PMID- 10895899
TI  - Pharmacokinetics of the insulin-sensitizing agent troglitazone in cats.
AB  - OBJECTIVE: To determine pharmacokinetics of troglitazone in healthy cats after
      i.v. and oral administration of a single dose of the drug. ANIMALS: 5 healthy
      ovariohysterectomized adult cats. PROCEDURE: Using a randomized crossover design,
      cats were given 5 mg of troglitazone/kg of body weight i.v. and 40 mg of
      troglitazone/kg orally. Blood and urine samples were collected after drug
      administration, and concentrations of troglitazone in plasma and urine were
      determined by use of high-performance liquid chromatography. RESULTS: Area-moment
      analysis was used to calculate pharmacokinetic variables. Terminal phase half
      life was 1.1 +/- 0.1 hours. Steady-state volume of distribution was 0.23 +/- 0.15
      L/kg. After i.v. administration, clearance was 0.33 +/- 0.04 L/h/kg. Drug was not
      detected in urine samples. Mean bioavailability of orally administered
      troglitazone was 6.9%. CONCLUSIONS AND CLINICAL RELEVANCE: The overall
      disposition of troglitazone in cats was similar to that reported in other
      species, including humans. Troglitazone has low and variable oral
      bioavailability. Clearance of the compound is moderate. Little if any unchanged
      troglitazone is excreted in urine; thus, metabolism and biliary excretion play
      predominant roles in elimination of the drug. On the basis of troglitazone
      pharmacokinetics in healthy cats, as well as on the basis of pharmacodynamics of
      the drug in humans and other animals, a regimen that uses a dosage of 20 to 40
      mg/kg administered orally once or twice per day to cats will produce plasma
      concentrations of the insulin-sensitizing agent that have been documented to be
      effective in humans.

PMID- 10895900
TI  - Bacterial contamination of suction tips used during surgical procedures performed
      on dogs and cats.
AB  - OBJECTIVE: To determine prevalence of bacterial contamination of surgical suction
      tips. SAMPLE POPULATION: Surgical tips used during 44 surgical procedures
      performed on 42 dogs and 2 cats. PROCEDURE: Surgical procedures were classified
      into 1 of 3 categories according to degree of bacterial contamination of the
      surgical site (clean, clean-contaminated, contaminated). Two sets of suction
      apparatuses were used for test and control suction tips. Test tips were used
      normally to suction blood and fluid, whereas control tips were placed on the
      surgical drapes but not in the surgical wound. Suction tips were collected
      aseptically and placed into thioglycolate broth tubes for qualitative aerobic and
      anaerobic bacterial culture at the end of each procedure. RESULTS: Test and
      control suction tips were contaminated with bacteria during 30 of 44 (68%)
      procedures. Staphylococcus spp were the predominant bacteria in tips used during
      clean and clean-contaminated surgeries. When surgery was performed on clean
      contaminated or contaminated wounds, prevalence of isolation of other bacteria
      such as Pseudomonas spp, Streptococcus spp, and Escherichia coli from both test
      and control suction tips was higher than for clean wounds. Mean time of
      procedures during which both test and control suction tips became contaminated
      was not significantly different from time of procedures during which neither tip
      became contaminated. CONCLUSION AND CLINICAL RELEVANCE: Surgical suction tips
      often become contaminated during standard veterinary surgical procedures. The
      risk of wound infection after surgery may be influenced by bacterial
      contamination of surgical suction tips.

PMID- 10895901
TI  - Evaluation of diet as a cause of gastric ulcers in horses.
AB  - OBJECTIVE: To measure pH, volatile fatty acid (VFA) concentrations, and lactate
      concentrations in stomach contents and determine number and severity of gastric
      lesions in horses fed bromegrass hay and alfalfa hay-grain diets. ANIMALS: Six 7
      year-old horses. PROCEDURE: A gastric cannula was inserted in each horse. Horses
      were fed each diet, using a randomized crossover design. Stomach contents were
      collected immediately after feeding and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24
      hours after feeding on day 14. The pH and VFA and lactate concentrations were
      measured in gastric juice Number and severity of gastric lesions were scored
      during endoscopic examinations. RESULTS: The alfalfa hay-grain diet caused
      significantly higher pH in gastric juice during the first 5 hours after feeding,
      compared with that for bromegrass hay. Concentrations of acetic, propionic, and
      isovaleric acid were significantly higher in gastric juice, and number and
      severity of nonglandular squamous gastric lesions were significantly lower in
      horses fed alfalfa hay-grain. Valeric acid, butyric acid, and propionic acid
      concentrations and pH were useful in predicting severity of nonglandular squamous
      gastric lesions in horses fed alfalfa hay-grain, whereas valeric acid
      concentrations and butyric acid were useful in predicting severity of those
      lesions in horses fed bromegrass hay. CONCLUSIONS AND CLINICAL RELEVANCE: An
      alfalfa hay-grain diet induced significantly higher pH and VFA concentrations in
      gastric juice than did bromegrass hay. However, number and severity of
      nonglandular squamous gastric lesions were significantly lower in horses fed
      alfalfa hay-grain. An alfalfa hay-grain diet may buffer stomach acid in horses.

PMID- 10895902
TI  - Use of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II), a
      liposomal cisplatin analogue, in cats with oral squamous cell carcinoma.
AB  - OBJECTIVE: To determine clinical response and toxic effects of cis-bis
      neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (L-NDDP) administered
      i.v. at escalating doses to cats with oral squamous cell carcinoma (SCC).
      ANIMALS: 18 cats with oral SCC. PROCEDURE: Cats that failed to respond to
      conventional treatment or had nonresectable tumors were included. Data included a
      CBC, serum biochemical analyses, urinalysis, cytologic examination of a fine
      needle aspirate of enlarged lymph nodes, and thoracic and oral radiographs for
      clinical staging. A starting dose (75 to 100 mg/m2 of L-NDDP) was administered
      i.v.. At 21-day intervals, subsequent doses increased by the rate of 5 or 10
      mg/m2. Response was evaluated every 21 days by tumor measurement and thoracic
      radiography. Quality of life was assessed by owners, using a performance status
      questionnaire. RESULTS: On average, cats received 2 treatments. Toxicoses
      included an intermittent, acute anaphylactoid-parasympathomimetic reaction,
      lethargy or sedation (< or = 24 hours), inappetence or signs of depression (< or
      = 72 hours), mild to moderate increase in hepatic enzyme activity, and melena.
      Pulmonary, renal, or hematopoietic abnormalities were not evident. Performance
      status surveys indicated normal behavior and grooming or decreased activity and
      self-care (19/20 assessments), ate well with or without assistance (15/20), and
      did not lose weight (15/20). Median survival time was 59.8 days (mean, 54.1
      days). CONCLUSIONS AND CLINICAL RELEVANCE: L-NDDP was ineffective for treatment
      of cats with oral SCC. None of the cats had a complete or partial remission.
      Acute toxicoses and poor therapeutic response limit therapeutic usefulness of L
      NDDP in cats, unless dosage, frequency, and administration procedures can be
      improved.

PMID- 10895903
TI  - Relationship between serum leptin immunoreactivity and body fat mass as estimated
      by use of a novel gas-phase Fourier transform infrared spectroscopy deuterium
      dilution method in cats.
AB  - OBJECTIVE: To validate a recently developed commercially available leptin
      radioimmunoassay (RIA) for use with feline serum and evaluate the relationship
      between serum leptin concentrations and body fat mass in domestic cats. ANIMALS:
      19 sexually intact male specific-pathogen-free domestic cats that weighed 3.8 to
      7.1 kg and were 1.1 to 3.5 years old. PROCEDURE: Specificity for feline leptin
      was evaluated by use of gel filtration chromatography and reverse-phase high
      performance liquid chromatography fractionation of serum. Body fat mass was
      determined by use of the deuterium oxide (D2O) dilution method. Serum water D2O
      enrichment was measured by use of gas-phase Fourier transform infrared
      spectroscopy. RESULTS: Body fat mass and percentage body fat ranged from 0.3 to
      2.3 kg and 7.5 to 34.9%, respectively. Serum leptin concentrations were lower in
      the unfed versus the fed state and ranged between 1.6 and 4.9 ng/ml human
      equivalent (HE); mean +/- SD value was 2.9 +/- 0.2 ng/ml HE. Leptin
      concentrations increased with increasing body fat mass and percentage of body
      fat. CONCLUSIONS: Leptin is in the serum of domestic cats in free (> 78%) and
      apparently bound forms. The relationship between body fat and serum leptin
      concentration was similar to that observed in humans and rodents and indicative
      of a lipostatic role for leptin in cats. Cats that have an overabundance of body
      fat appear to be less sensitive to the weight-normalizing action of leptin than
      cats of ideal body condition.

PMID- 10895904
TI  - In vitro effects of nonsteroidal anti-inflammatory drugs on cyclooxygenase
      activity in dogs.
AB  - OBJECTIVE: To establish an in vitro assay and determine the differential
      suppressive activity of non steroidal anti-inflammatory drugs (NSAID) on
      cyclooxygenase (COX)-1 and COX-2 isoenzymes in dogs. PROCEDURE: COX activity was
      evaluated in the presence and absence of 4 NSAID (meloxicam, tolfenamic acid,
      carprofen, and ketoprofen), using a canine monocyte/macrophage cell line that
      constitutively expresses COX-1, but can be induced to express COX-2 when
      incubated with lipopolysaccharide. Inhibition of prostaglandin E2 TPGE2)
      synthesis by each NSAID was measured by enzyme immunoassay and attributed to
      specific COX-1 or COX-2 activity through assessment of COX messenger RNA
      expression by use of northern blot analysis and reverse transcription-polymerase
      chain reaction (RT-PCR). The COX selectivity of each drug was evaluated from dose
      response curves by calculating a ratio (COX-1:COX-2) of inhibitory concentration
      values on the basis of concentrations that reduced PGE2 by 50% in each COX model.
      RESULTS: Meloxicam and tolfenamic acid preferentially inhibited COX-2, with
      meloxicam inhibiting COX-2 activity 12 times more effectively than COX-1
      activity. Carprofen was only 1.75 times more selective for COX-2 than for COX-1,
      and ketoprofen was slightly more selective for COX-1. CONCLUSIONS: COX-1 and COX
      2 were differentially sensitive to inhibition in vitro by NSAID. Meloxicam and
      tolfenamic acid were selective for COX-2. Effects of carprofen and ketoprofen
      approached equipotency against both isoenzymes. Selective COX-2 inhibitors are a
      new class of drugs with anti-inflammatory effects similar to conventional NSAID
      but with fewer adverse effects. Development of these agents for veterinary use
      would be facilitated by the convenience of using a canine cell line as a model
      system to screen COX-1 and COX-2 inhibitor activities in vitro.

PMID- 10895905
TI  - Pharmacokinetics of penicillin G procaine versus penicillin G potassium and
      procaine hydrochloride in horses.
AB  - OBJECTIVE: To compare the pharmacokinetics of penicillin G and procaine in
      racehorses following i.m. administration of penicillin G procaine (PGP) with
      pharmacokinetics following i.m. administration of penicillin G potassium and
      procaine hydrochloride (PH). ANIMALS: 6 healthy adult mares. PROCEDURE: Horses
      were treated with PGP (22,000 units of penicillin G/kg of body weight, i.m.) and
      with penicillin G potassium (22,000 U/kg, i.m.) and PH (1.55 mg/kg, i.m.). A
      minimum of 3 weeks was allowed to elapse between drug treatments. Plasma and
      urine penicillin G and procaine concentrations were measured by use of high
      pressure liquid chromatography. RESULTS: Median elimination phase half-lives of
      penicillin G were 24.7 and 12.9 hours, respectively, after administration of PGP
      and penicillin G potassium. Plasma penicillin G concentration 24 hours after
      administration of penicillin G potassium and PH was not significantly different
      from concentration 24 hours after administration of PGP. Median elimination phase
      half-life of procaine following administration of PGP (15.6 hours) was
      significantly longer than value obtained after administration of penicillin G
      potassium and PH (1 hour). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest
      that i.m. administration of penicillin G potassium will result in plasma
      penicillin G concentrations for 24 hours after drug administration comparable to
      those obtained with administration of PGP Clearance of procaine from plasma
      following administration of penicillin G potassium and PH was rapid, compared
      with clearance following administration of PGP.

PMID- 10895906
TI  - Failure to detect bovine immunodeficiency virus contamination of stud bull
      spermatozoa, blood leukocytes, or semen leukocytes in samples supplied by
      artificial insemination centers.
AB  - OBJECTIVE: To determine whether bovine immunodeficiency virus (BIV) infection
      could be detected in spermatozoa, blood leukocytes, or semen leukocytes from stud
      bulls in artificial insemination centers. ANIMALS: 30 bulls at 3 artificial
      insemination centers. PROCEDURE: Polymerase chain reaction testing that used 3
      sets of primer pairs targeting pol and env regions of the BIV proviral genome was
      performed on DNA extracted from semen leukocytes, spermatozoa, and blood
      leukocytes from each bull. Southern blot analysis was performed to increase
      sensitivity of detection. Western blot analysis of plasma samples was used to
      detect antibodies against BIV. RESULTS: BIV provirus was not detected in DNA
      samples obtained from semen leukocytes, spermatozoa, or blood leukocytes, and
      antibodies against BIV were not detected. CONCLUSIONS AND CLINICAL RELEVANCE:
      Contrary to our report of high point prevalence of BIV contamination of semen
      from a single artificial insemination center, bulls of the study reported here
      did not appear to be infected. Maximum risk of BIV infection in similar bulls was
      estimated at 10% with a confidence level of 95%.

PMID- 10895907
TI  - Effects of dietary fructooligosaccharide on selected bacterial populations in
      feces of dogs.
AB  - OBJECTIVE: To evaluate fecal concentrations of selected genera of colonic
      bacteria in healthy dogs, and to investigate effects of dietary
      fructooligosaccharides (FOS) on those bacterial populations. ANIMALS: 6 healthy
      adult Beagles. PROCEDURE: Dogs were randomly assigned to 2 groups of 3 and fed an
      unsupplemented diet for 370 days. After 88 days, fecal samples were collected.
      Another fecal sample was collected from each dog 282 days later. Group A then
      received a diet supplemented with FOS, and group B continued to receive the
      unsupplemented diet. Twenty-eight to 29 days later, fecal samples were collected.
      Diets were switched between groups, and fecal samples were collected 31 and 87
      days later. Concentrations of Bifidobacterium spp, Lactobacillus spp, Clostridium
      spp, Bacteroides spp, and Escherichia coli in freshly collected feces were
      determined. Effects of diet and time on bacterial concentrations were compared
      between groups. RESULTS: Bifidobacterium spp and Lactobacillus spp were
      inconsistently isolated from feces of dogs fed either diet. Sequence of diet
      significantly affected number of Bacteroides spp subsequently isolated from
      feces, but diet had no effect on numbers of Clostridium spp or E coli.
      CONCLUSIONS AND CLINICAL RELEVANCE: Some genera of bacteria (eg, Bifidobacterium)
      believed to be common components of colonic microflora may be only sporadically
      isolated from feces of healthy dogs. This deviation from expected fecal flora may
      have implications for the effectiveness of supplementing diets with prebiotics.

PMID- 10895908
TI  - Effect of age on immunocytochemical staining characteristics of adenohypophyseal
      cells in Mongolian pony mares and stallions.
AB  - OBJECTIVE: To determine the effect of age on immunocytochemical staining
      characteristics of adenohypophyseal cells of Mongolian pony mares and stallions.
      ANIMALS: 35 Mongolian ponies. PROCEDURE: Pituitary glands from 1- to 22-year-old
      horses of both sexes were collected at a commercial slaughterhouse in China and
      allocated into 7 groups according to age and sex: prepubertal stallions (n = 5; 1
      to 2 years old), young stallions (6; 3 to 7 years old), middle-aged stallions (4;
      10 to 12 years old), old stallions (5; 15 to 22 years old), young mares (3; 3 to
      7 years old), middle-aged mares (5; 10 to 12 years old), and old mares (7; 15 to
      22 years old). Pituitary glands were processed for microscopy, and sections were
      immunocytochemically stained for various pituitary hormones. The percentages and
      cell areas of 6 types of adenohypophyseal cells were determined by use of
      morphometry. RESULTS: Age-related alterations in adenohypophyseal cells were
      detected in horses > 15 years old. Percentage of somatotrophs decreased with age
      regardless of sex, and percentage of lactotrophs increased with age in stallions.
      In old mares, percentage of follicle-stimulating hormone cells increased, whereas
      cell area of follicle-stimulating hormone and luteinizing hormone cells
      decreased. Differences between sexes for percentage of somatotrophs and
      lactotrophs, and cell area of follicle-stimulating hormone and luteinizing
      hormone cells were not evident in old horses. CONCLUSIONS AND CLINICAL RELEVANCE:
      Differences among percentages and cell areas of pituitary cell types in old
      horses may be associated with degeneration of the sex organs.

PMID- 10895909
TI  - Comparison of the trotting gaits of Labrador Retrievers and Greyhounds.
AB  - OBJECTIVE: To compare the trotting gaits of Labrador Retrievers and Greyhounds to
      determine whether differences in locomotion are attributable to differences in
      their manner of moving or to body size and shape differences between these 2
      breeds. ANIMALS: 8 healthy 5-month-old Greyhounds and 5 healthy Labrador
      Retrievers between 6 and 18 months old. PROCEDURE: A series of 4 force platforms
      was used to record independent ground reaction forces on the forelimbs and hind
      limbs during trotting. Values of stride parameters were compared between breeds
      before and after normalization for size differences. Standard values of absolute
      and normalized stride period and stride length were determined from linear
      regressions of these parameters on relative (normalized) velocity. Forces were
      normalized to body weight and compared at the same relative velocity. RESULTS:
      Greyhounds used fewer, longer strides than the Labrador Retrievers to travel at
      the same absolute speed. After normalization for body size differences, most
      measurable differences between breeds were eliminated. Subtle differences that
      did persist related to proportion of the stride that the forefoot was in contact
      with the ground, timing of initial hind foot contact relative to initial forefoot
      contact, and distribution of vertical force between the forelimbs and hind limbs.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that apparent differences in
      the trotting gait between Labrador Retrievers and Greyhounds are mainly
      attributable to differences in size, and that dogs of these 2 breeds move in a
      dynamically similar manner at the trot.

PMID- 10895911
TI  - Development and use of a polymerase chain reaction-based diagnostic test for the
      causal mutation of progressive retinal atrophy in Cardigan Welsh Corgis.
AB  - OBJECTIVE: To develop an allele-specific polymerase chain reaction (ASPCR)-based
      diagnostic test for the mutation in the cyclic guanosine monophosphate
      phosphodiesterase alpha subunit gene (PDE6A) that causes the rcd3 form of
      progressive retinal atrophy (PRA) in Cardigan Welsh Corgis. ANIMALS: 1 affected
      homozygote, 1 unaffected carrier, 1 genotypically normal dog, and 500 unknown-PRA
      status Cardigan Welsh Corgis. PROCEDURE: Control blood samples were collected
      from Cardigan Welsh Corgis of known PRA status (ie, affected homozygote,
      unaffected carrier, and a genotypically normal dog) for test development. Test
      blood samples were collected from 500 Cardigan Welsh Corgis of unknown PRA
      status. Genomic DNA was used as a template in ASPCR. One pair of primers was
      designed to specifically amplify only the mutant allele, and another set to
      amplify only the wildtype allele. The PCR conditions were adjusted to ensure each
      reaction was 100% specific. RESULTS: The PCR conditions were identified so that
      each ASPCR only amplified the allele it was designed to amplify. Of the 500
      Cardigan Welsh Corgis tested using the newly developed ASPCR, 457 were homozygous
      for the normal allele (genotypically normal), 43 were heterozygous
      (phenotypically normal carriers), and none were homozygous for the mutant allele.
      CONCLUSION AND CLINICAL RELEVANCE: A rapid, ASPCR diagnostic test able to detect
      the PDE6A gene mutation responsible for the rcd3 form of PRA in Cardigan Welsh
      Corgis was developed. The test provides a useful service for Cardigan Welsh Corgi
      breeders and will enable them to prevent the birth of homozygote mutant dogs.

PMID- 10895910
TI  - Effects of various adjuvants on efficacy of a vaccine against Streptococcus bovis
      and Lactobacillus spp in cattle.
AB  - OBJECTIVE: To determine efficacy of vaccines incorporating QuilA, alum, dextran
      combined with mineral oil, or Freund adjuvant for immunization of feedlot cattle
      against Streptococcus bovis and Lactobacillus spp. ANIMALS: 24 steers housed
      under feedlot conditions. PROCEDURE: Steers were randomly assigned to 4
      experimental groups and a control group. Animals in experimental groups were
      inoculated on days 0 and 26 with vaccines containing Freund adjuvant (FCA),
      QuilA, dextran combined with mineral oil (Dex), or alum as adjuvant. Serum anti-S
      bovis and anti-Lactobacillus IgG concentrations were measured, along with fecal
      pH, ruminal fluid pH, and number of S bovis and Lactobacillus spp in ruminal
      fluid. RESULTS: Throughout the study, serum anti-S bovis and anti-Lactobacillus
      IgG concentrations for animals in the Dex, QuilA, and alum groups were similar to
      or significantly higher than concentrations for animals in the FCA group. Serum
      anti-S bovis and anti-Lactobacillus IgG concentrations were significantly
      increased on days 26 through 75 in all 4 experimental groups, and there was a
      linear relationship between anti-S bovis and anti-Lactobacillus IgG
      concentrations. For animals in the QuilA and Dex groups, mean pH of feces
      throughout the period of experiment were significantly higher and numbers of S
      bovis and Lactobacillus spp in ruminal fluid on day 47 were significantly lower
      than values for control cattle. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggest that immunization of feedlot steers against S bovis and Lactobacillus spp
      with vaccines incorporating Freund adjuvant, QuilA, dextran, or alum as an
      adjuvant effectively induced high, long-lasting serum anti-S bovis and anti
      Lactobacillus IgG concentrations. Of the adjuvants tested, dextran may be the
      most effective.

PMID- 10895912
TI  - Flow cytometric analysis of nuclear DNA for sex identification in three
      psittacine species.
AB  - OBJECTIVE: To evaluate flow cytometric analysis for sex identification in 3
      psittacine species, establish reference values for blood cell DNA content for
      each species, and determine effects of sample storage on DNA content. ANIMALS: 36
      orange-winged Amazon parrots, 41 budgerigars, and 39 cockatiels. PROCEDURE: Blood
      samples were stained and analyzed by use of flow cytometry to measure cellular
      DNA content. Samples were analyzed immediately after collection and after being
      stored at 4 C for 48 and 72 hours. RESULTS: Mean DNA content (picograms per cell)
      was 3.248 for Amazon parrots, 2.702 for budgerigars, and 2.946 for cockatiels;
      DNA concentrations in samples analyzed immediately overlapped in a male and a
      female Amazon parrot and among 19 cockatiels. For budgerigars, DNA overlap
      between sexes was not detected in samples analyzed immediately or after storage
      for 72 hours. Sex was identified correctly in 94.4% of Amazon parrots, 100% of
      budgerigars, and 51.3% of cockatiels. For both sexes, DNA content in samples
      analyzed immediately was significantly different from that of stored samples.
      CONCLUSIONS AND CLINICAL RELEVANCE: Flow cytometric analysis was accurate for sex
      identification of Amazon parrots and budgerigars. Sample storage at 4 C for 48 or
      72 hours caused variability in DNA content.

PMID- 10895914
TI  - Emergency medical services providers and weapons in the prehospital setting.
AB  - OBJECTIVES: To investigate emergency medical services (EMS) providers' experience
      with weapons encountered while working, and evaluate the training they have
      received regarding searching for and confiscating weapons in the field. METHODS:
      This was a descriptive, cross-sectional survey anonymously completed by a
      convenience sample of EMS providers in the metropolitan Boston and Los Angeles
      (LA) areas. RESULTS: Of 2,672 surveys distributed, 2,224 (83%) were returned.
      Forty-two percent of the respondents (39% of Boston and 46% of LA) reported
      searching patients for weapons, and 62% (51% of Boston and 76% of LA) reported
      finding weapons. The LA respondents were more likely than the Boston respondents
      to have found a firearm. Twenty-seven percent of the respondents reported they
      had found more than five weapons in their careers. One thousand seven hundred
      seventy-two (80%) providers replied that they would report discovered weapons,
      most frequently to law enforcement personnel. Providers with higher EMS education
      and ones who received weapons-related training were more likely to search for,
      find, and report weapons. Four hundred fifty-one (20%) respondents reported
      receiving formal weapons-related training, 291 (13%) considered their initial EMS
      training on weapons-related topics to be adequate, and 292 (13%) considered their
      continuing education in these areas adequate. CONCLUSIONS: These data suggest
      that weapons encountered in the field are a widespread problem for EMS providers.
      Although many EMS providers search for and find weapons on their patients, most
      of them feel they have been inadequately trained in this area. Prospective
      studies are needed to document the actual incidence of weapon encounters in the
      prehospital setting. Multidisciplinary discussions are needed to address the
      above issues.

PMID- 10895913
TI  - Prehospital use of analgesia for suspected extremity fractures.
AB  - INTRODUCTION: Pain and its control have been studied extensively in the emergency
      department. Numerous studies indicate that inadequate treatment of pain is
      common, despite the availability of myriad analgesics. It has been suggested that
      oligoanesthesia is also a common practice in the prehospital setting. OBJECTIVE:
      To assess the use of prehospital analgesia in patients with suspected extremity
      fracture. METHODS: Emergency medical services (EMS) call reports were reviewed
      for all patients with suspected extremity fractures treated from June 1997 to
      July 1998 in a midwestern community with a population base of 223,000. Data
      collected included demographic information, mechanism of injury, medications
      given, and field treatment. Standing orders for administration of analgesia were
      available and permitted paramedics to give either morphine sulfate or nitrous
      oxide per protocol. RESULTS: The EMS call reports were analyzed for 1,073
      patients with suspected extremity fractures. The mean patient age was 47 years.
      Accidental injuries comprised 86.5% of those reviewed. Suspected leg fractures
      were most common (20%), followed by hips (18%), arms (11%), knees (10%), ankles
      (9%), shoulders (7.2%), hands (5.5%), and wrists (5.3%). Multiple trauma and
      assorted broken digits accounted for the remaining 14%. The most common
      mechanisms of injury were: fall (43%), motor vehicle collision (21%), and human
      assault (10%). Intravenous lines were placed in 9.4% of patients; 17% received
      ice packs; 16% received bandage/dressings; 25% received air splints; and 19% were
      fully immobilized. Analgesia was administered to 18 patients (1.8%): 16 patients
      received nitrous oxide and two received morphine. CONCLUSION: Administration of
      analgesics to prehospital patients with suspected fractures was rare. Prehospital
      identification and treatment of pain for patients with musculoskeletal trauma
      could be improved.

PMID- 10895915
TI  - Physician field response: a national survey.
AB  - OBJECTIVE: To assess the availability, scope of practice, and training of
      physician field response (PFR) units for emergency medical services (EMS) systems
      in the United States. METHODS: The physician medical directors of EMS systems in
      the 125 most populous U.S. cities were surveyed by mail, with a second mailing
      and phone follow-up to nonresponders. In cities that listed multiple services, a
      survey was sent to each. RESULTS: One hundred sixty-eight surveys were mailed,
      and 121 responses were received (72%), representing 109 of the 125 cities (87%).
      Seventy-seven cities (71%) reported having no PFR capability. Of the 32 (29%)
      with some type of PFR, two reported having a dedicated field response unit, while
      30 had an "on-call" system from the hospital or home. Staffing patterns were
      highly variable, with no dominant pattern. The number of annual PFR responses
      ranged from 0 to 10,000 (median 15, IQR 3-200). All systems reported that their
      PFR unit was well accepted by EMS providers. The following scope-of-practice
      items were reported (n = 30): physician triage, 30 teams (94%); on-scene medical
      direction, 14 (47%); amputation, six (20%); tube thoracostomy, 12 (40%); and
      blood administration, 29 (97%). The following training requirements for physician
      team members were reported (n = 32): incident command system, 15 (47%); emergency
      vehicle operations, 12 (38%); hazardous materials, 13 (41%); vehicle
      rescue/extrication, seven (22%); confined space medicine, four (13%); and none 12
      (38%). CONCLUSION: There is a wide variability in the availability, training, and
      scope of practice of PFR units across the country. No standardization or trends
      could be detected.

PMID- 10895916
TI  - Emergency response team: Hurricane Georges in Key West.
AB  - Hurricane Georges (category 2) struck Key West, Florida, on September 25, 1998.
      Lower Florida Keys Hospital, which serves Key West and the Lower Keys, had
      previously been evacuated of inpatients and staff. An emergency response team
      composed of three emergency medicine (EM) physicians and four EM nurses was sent
      at the request of the state to maintain emergency department (ED) operations at
      the hospital. Eighty-six patients presented to the ED during the 72-hour period.
      Medical problems accounted for the majority of visits (52.3%), with minor trauma
      next (41.9%). Initially, patients requiring hospitalization were evacuated, but
      as the storm neared, this was stopped. Six patients required hospitalization at
      Lower Florida Keys Hospital during the period that evacuations were unavailable.
      Four deaths occurred during the 24-hour period. Complicating factors included
      environmental conditions, limited laboratory and radiologic studies, limited
      medication stocks, and closure of local pharmacies before and after the
      hurricane. More than 300 nursing home patients were housed at the nearby jail
      shelter. Knowledge of such high-risk groups that remain in the vicinity is
      crucial to planning a response plan.

PMID- 10895917
TI  - Cancellation of responding ALS units by BLS providers: a national survey.
AB  - OBJECTIVE: In many emergency medical services (EMS) systems, personnel without
      advanced life support (ALS) training are authorized to cancel responding ALS
      units before the ALS personnel arrive and examine the patient. This study was
      conducted to examine these cancellations in major U.S. cities. METHODS: A survey
      was mailed to the physician medical directors of the EMS services of the 125
      largest U.S. cities, with telephone follow-up of nonresponders. The survey
      requested information on system structure, and on policies governing cancellation
      of responding ALS units by non-ALS personnel. RESULTS: Ninety-four cities
      responded (75%), from 35 states. Nineteen systems (20%) are all-ALS with no basic
      life support (BLS) tier, and these were eliminated. Of the remaining 75 systems,
      eight (11%) use BLS ambulances (BLS-A), 35 (47%) use BLS first responders (BLS
      FR), and 32 (43%) use both. Of these 75 systems, 60 (80%) allow cancellation of
      responding ALS units by BLS personnel. Only 24 of these (40%) have written
      protocols for such cancellations, and only 12 of those (50%) involve specific
      medical criteria, with two (8%) relying on the best judgment of the BLS personnel
      with no medical criteria, and another eight (33%) allowing cancellation only for
      logistic reasons. Of the 60 systems that permit cancellation, 13 (22%) perform
      some type of medical oversight review of all such calls, 26 (43%) review some
      such calls (median 10%, range 2-80% for the 19 systems specifying a percentage),
      15 (25%) do not review any, and six did not specify. CONCLUSIONS: Fewer than half
      of the surveyed EMS systems that permit non-ALS personnel to cancel responding
      ALS units use written protocols to guide these decisions, and only half of those
      protocols utilize specific medical criteria. Medical oversight review of these
      calls is highly variable, with many systems reviewing few or none of these
      cancellations.

PMID- 10895918
TI  - The lay public's expectations of prearrival instructions when dialing 9-1-1.
AB  - OBJECTIVE: To determine whether the lay public expects public safety answering
      points (PSAPs) to provide prearrival instructions. METHODS: Two thousand
      telephone numbers were randomly generated from all listed residential numbers in
      a county containing urban, suburban, and rural communities served by 26 enhanced
      9-1-1 PSAPs. Only a minority of the PSAPs provided prearrival instructions.
      Research assistants made two attempts to contact an individual at each telephone
      number. A survey was administered to any person who answered the telephone
      provided the person was at least 18 years of age and gave verbal consent. The
      respondents were asked their age, level of education, and gender. They were also
      asked what number they would call for first aid or an ambulance and whether they
      would expect telephone instructions from the dispatcher if a close relative was
      choking, not breathing, bleeding, or giving birth. RESULTS: One thousand twenty
      four individuals were successfully contacted; and 524 (51%) were at least 18
      years of age and agreed to participate. The respondents' mean age was 50
      (standard deviation 19 years). Sixty-five percent of the respondents were female;
      and 90% had at least a high school diploma. Only 37% had previously called 9-1-1
      (nine-one-one) for an emergency. Ninety-seven percent said they would dial either
      9-1-1 (85%) or 9-11 (nine-eleven) (12%) in an emergency. Seventy-six percent (95%
      CI: 73%-80%) expected prearrival instructions for all four medical conditions.
      Specifically, prearrival instructions were expected by: 88% for choking (95% CI:
      85%-90%), 87% for not breathing (95% CI: 84%-90%), 89% for bleeding (95% CI: 86%
      91%), and 88% for childbirth (95% CI: 86%-91%). Ninety-nine of 117 respondents
      (81%) served by a PSAP that did not provide prearrival instructions expected to
      receive phone instructions for all four emergencies. Logistic regression revealed
      that knowing to dial 9-1-1 or 9-11 in an emergency was the only significant
      predictor of prearrival instruction expectation [p < 0.03, odds ratio 3.4 (95%
      CI: 1.16-9.78)]. Age, gender, service by a PSAP providing prearrival
      instructions, and level of education were not predictive. CONCLUSION: The lay
      public expects prearrival instructions when calling 9-1-1, although they may not
      currently receive this service.

PMID- 10895919
TI  - Can current EMS dispatch protocols identify layperson-reported sentinel
      conditions?
AB  - INTRODUCTION: Managed care organizations are seeking opportunities to capitate
      for emergency medical services (EMS). These and others pressures are motivating
      EMS planners to find innovative ways to redeploy existing EMS resources. A
      successful redeployment of resources implies a mechanism for more carefully
      matching EMS resources to need than currently exists. OBJECTIVE: To determine
      whether the methods dispatchers currently use to assign nature codes (NCs) and
      severity codes (SCs) also can distinguish between patients with important
      sentinel conditions and those without. METHODS: This was a six-month prospective
      study (June to November 1997). Portland Fire Bureau (PFB) paramedic units
      documented dispatcher-assigned NCs and SCs and the presence or absence of study
      established sentinel findings. The PFB paramedics also verified or corrected
      dispatcher-assigned NCs and SCs using dispatch algorithms identical to those in
      use at this urban dispatch center. Cross-tabulation tables (SPSS version 6.1)
      with chi-square statistics were established to illustrate the relationship
      between SC strata within specific NCs and the presence or absence of sentinel
      findings. RESULTS: One thousand two hundred eighty-five usable cases fell into 25
      unique NCs. The designation SC 1 (emergent) was assigned by the dispatcher 307
      (24%) times, SC 3 (urgent) was assigned 907 (71%) times, and SC 9 (neither
      emergent nor urgent) was assigned 26 (2%) times. The SC was missing 45 (3%)
      times. The PFB records were matched to 1,040 (82%) dispatch records. Sentinel
      conditions were identified in 411 (40%) of these cases. Eight (32%) of 25 NCs
      were stratified into two or more levels of dispatcher-determined SCs. One cross
      tabulation table for each of these eight NCs was developed to display the
      relationship between SC strata and the presence or absence of a sentinel
      condition. Five tables produced statistically significant chi-square tables (p <
      0.05). None achieved the study-specified level of 95% sensitivity. CONCLUSION:
      Current dispatcher-assigned NCs and SCs do not appear adequate to detect callers
      with study-developed sentinel criteria.

PMID- 10895920
TI  - Ability of EMT-Bs to determine which wounds can be repaired in the field.
AB  - INTRODUCTION: In certain emergency medical services (EMS) systems, emergency
      medical technicians-paramedics (EMT-Ps) repair lacerations in the field. This
      practice is supported by studies showing equivalence between nonphysicians and
      physicians regarding infection rates and cosmetic outcomes. OBJECTIVE: To
      evaluate the ability of emergency medical technicians-basic (EMT-Bs) to identify
      wounds repairable in the field or requiring tetanus prophylaxis. METHODS: This
      was a prospective, double-blind convenience sample study at an urban teaching
      hospital. Eleven EMT-B volunteers, trained by a one-hour lecture and bedside
      teaching, evaluated lacerations for prehospital repair by answering three
      questions: Could this wound be repaired in the field, and if no, why not? If on
      an adult forearm, could this wound be repaired in the field, and if no, why not?
      Does this patient need tetanus prophylaxis, and if no, why not? A blinded
      principal investigator also answered these questions, and a person uninvolved in
      the study correlated results. Statistical evaluation was performed using kappa
      statistics. RESULTS: The EMT-Bs identified 17 of 17 potentially repairable wounds
      and 163 of 163 wounds excluded from prehospital repair. Placing the wound on the
      forearm, the EMT-Bs identified 82 of 87 potentially repairable wounds and 93 of
      93 wounds excluded from prehospital repair (sensitivity 94%, specificity 100%,
      positive predictive value 100%, negative predictive value 95%, kappa 0.97). For
      five of five wounds, physicians disagreed with the EMT-Bs and thought the wound
      repairable prehospital. The EMT-Bs and physicians agreed on individual wound
      exclusion criteria in 207 of 239 (86.6%) instances. Finally, the EMT-Bs
      identified 108 of 108 patients requiring tetanus prophylaxis. CONCLUSIONS: Basic
      EMTs can accurately identify wounds eligible for prehospital repair and/or
      requiring tetanus prophylaxis.

PMID- 10895921
TI  - Maximizing comfort and minimizing ischemia: a comparison of four methods of
      spinal immobilization.
AB  - OBJECTIVE: To determine which of four methods of spinal immobilization causes the
      least ischemic pain. METHODS: A prospective, nonblinded comparative trial was
      conducted at a statewide emergency medical services training facility using a
      convenience sample of emergency medical technician students. After lying
      motionless for 10 minutes, students evaluated each device using a 10-centimeter
      visual analog scale. Subjective comfort was used as a measure of ischemia.
      RESULTS: Comfort scores were significantly different for all methods (F = 101, p
      < 0.001). A backboard padded with a gurney mattress and eggcrate foam (the
      equivalent of a spinal rehabilitation bed) caused the least ischemic pain (9.6
      cm, 95% CI, 8.9 to 9.8 cm). A backboard padded with a gurney mattress was the
      second most comfortable device (7.0 cm, 95%/CI, 6.4 to 7.4 cm). A backboard
      padded with a folded blanket was the third most comfortable (3.3 cm, 95% CI, 2.6
      to 4.9 cm). The backboard alone caused the most pain (0.8 cm, 95% CI, 0.7 to 2.1
      cm). CONCLUSION: Increasing the amount of padding on a backboard decreased the
      amount of ischemic pain caused by immobilization.

PMID- 10895922
TI  - Medication calculation skills of practicing paramedics.
AB  - OBJECTIVE: To assess the medication calculation skills among a group of
      practicing paramedics, the types of computations they find most difficult, and
      the relationship between drug calculation skills and various demographic
      characteristics. METHODS: A demographic survey and a ten-item drug calculation
      examination were administered to a convenience sample of 109 practicing
      paramedics representing a cross-section of emergency medical services (EMS)
      system characteristics in North Carolina. Examinations were scored independently
      by two graders and error types were assigned to incorrect responses. Examination
      results were then correlated with demographic and EMS system characteristics.
      RESULTS: Overall performance on the drug calculation examination was poor. The
      mean score was 51.4% (SD 27.4). Intravenous flow rate problems and medication
      bolus problems were calculated correctly in 68.8% of the cases, followed by non
      weight-based medication infusions (33.9%), weight-based medication infusions
      (32.5%), and percentage-based medication infusions (4.5%). Examination scores
      were higher among paramedics with college level education, but scores were lower
      among paramedics with more years of EMS experience. Conceptual errors (i.e.,
      errors in setting up the problem) were more prevalent than mathematical errors,
      errors in weight conversion, or errors in unit conversion (e.g., grams to
      milligrams). The participants reported that drug calculations were infrequently
      performed in daily practice and were rarely a topic of continuing education
      programs. CONCLUSION: Similar to findings among other allied health professions,
      medication calculation skills were found to be lacking among a group of
      practicing paramedics. In addition, the paramedics reported infrequent
      opportunities to perform this skill in the clinical setting and that medication
      calculations were not a routine part of EMS continuing education programs.

PMID- 10895923
TI  - Health care facility preparation for weapons of mass destruction.
AB  - Weapons of mass destruction (WMD) are a threat that all health care facilities
      must be prepared for. Every health care facility is a vital part of the community
      response system and must be ready to respond. A terrorist attack using WMD can
      occur in any location, urban or rural. Private vehicles or buses may transport
      the majority of patients, with only a small percentage arriving by emergency
      medical services. Most will go to the hospitals closest to the incident, even if
      this results in overcrowding. Others will go directly to their private
      physicians' offices or primary hospitals, even if these facilities are not part
      of the local disaster plan. Most of these victims will not be decontaminated
      before arrival. If a hospital allows any of these patients in, the staff may
      become ill from the toxic exposure and the facility may require closure for
      decontamination. Since the risk is universal, all health care facilities must
      plan for the care of victims of a WMD incident. They must plan for communications
      that allow local government to transmit alerts regarding the emergency. Health
      care facilities must also communicate their status and emergency needs to local
      officials during the emergency. They must be prepared to establish a single entry
      control point and attempt to secure all other entrances. They must be able to
      establish a patient decontamination team from on-duty staff with only a few
      minutes' notice at any time of the day or night.

PMID- 10895924
TI  - Acute stroke: implications for prehospital care. National Association of EMS
      Physicians Standards and Clinical Practice Committee.

PMID- 10895925
TI  - Managed care and EMS: an interrogatory model to assist communities in evaluating
      innovative partnerships. National Association of EMS Physicians Managed Care Task
      Force.

PMID- 10895926
TI  - Application of the assay of aflatoxins by liquid chromatography with fluorescence
      detection in food analysis.
AB  - HPLC using fluorescence detection has already become the most accepted method for
      the determination of aflatoxins due to its several advantages over other
      analytical methods. Both normal- and reversed-phase HPLC can be used. However the
      reversed-phase HPLC methods are more popular. Liquid chromatographic
      determination of aflatoxins using fluorescence detection and its application in
      food analysis is reviewed in this article.

PMID- 10895927
TI  - Determination of aflatoxins in food by overpressured-layer chromatography.
AB  - Legislative measures for monitoring and control of aflatoxin levels in foods and
      foodstuffs have been introduced in many countries. The aim of the present work
      was to make developments in the field of aflatoxin analysis, focusing upon the
      use of overpressured-layer chromatography (OPLC) for quantitative determination.
      OPLC methods have been developed for the determination of aflatoxins B1, B2, G1,
      G2 in different foods. These methods are suitable for sample clean-up and
      separation as well. Using OPLC we could analyze 10 samples simultaneously. The
      methods were investigated with fish, corn and wheat samples spiked with 2-10 ng/g
      aflatoxins. Quantitative evaluation of aflatoxins was accomplished by
      densitometry. Average recoveries from each food were greater than 73%. The OPLC
      technique seems to be a rapid, reproducible and cost-effective analysis for
      quantitative determination of aflatoxins in foods.

PMID- 10895928
TI  - Chromatographic determination of the mycotoxin patulin in fruit and fruit juices.
AB  - Patulin is a mycotoxin produced by several fungal species of the genera
      Penicillium and Aspergillus, but principally by Penicillium expansum on fruit
      such as apples. The occurrence of patulin as a natural contaminant of apple juice
      is a worldwide problem and international recommendations and regulations have
      been made for maximum levels permitted in consumer products. This paper reviews
      currently available analytical methods for its determination in fruit and fruit
      juices. Of these, HPLC with ultraviolet or, preferably, photodiode array
      detection is most widely used, although GC and TLC methods have also been
      described.

PMID- 10895929
TI  - Simultaneous determination of trichothecene mycotoxins and zearalenone in cereals
      by gas chromatography-mass spectrometry.
AB  - Trichothecene mycotoxins are commonly distributed in crop fields in the world,
      and zearalenone has been found in cereals. Rapid and accurate methods for the
      determination of these mycotoxins is required to prevent the intoxication of
      humans, and to contribute to the supply of safe foods and feeds for human and
      livestock. Gas chromatography-mass spectrometry (GC-MS) is a useful method for
      the determination of these toxins. We describe here our current GC-MS analysis
      for the simultaneous determination of trichothecenes and zearalenone contaminants
      in cereals.

PMID- 10895930
TI  - Solid-phase extraction applied to the determination of ochratoxin A in wines by
      reversed-phase high-performance liquid chromatography.
AB  - A reversed-phase high-performance liquid chromatographic method is described for
      the analysis of Ochratoxin A at low microg l(-1) levels in samples of
      artificially contaminated wines. The method involves solid-phase extraction of
      samples using octadecylsilane cartridges and an additional preconcentration step
      prior to chromatography with isocratic elution and fluorimetric detection. The
      method was evaluated for accuracy and precision with relative standard deviations
      lower than 10%. Recoveries of ochratoxin A added to commercial wines over the
      range 0.1-3.0 microg l(-1) were higher than 80% in the assays. The performance of
      the octadecylsilane cartridge method tested compared very favourably with results
      of other published studies of ochratoxin A which use immunoaffinity columns or
      solvent extraction techniques.

PMID- 10895931
TI  - Regulatory problems caused by contamination, a frequently overlooked cause of
      veterinary drug residues.
AB  - The occurrence of violative residues of veterinary medicines and other,
      unauthorised, drugs in food of animal origin is an issue of popular concern
      within the European Union. Violations can occur as a result of improper use of a
      licensed product or through the illegal use of an unlicensed substance. However,
      a "violative" analytical result does not necessarily mean that abuse has
      occurred. Contamination of animal feedingstuffs, environmental contamination and
      animal-to-animal transfer of drugs can also cause residue violations. This paper
      reviews these inadvertent causes of residues violations in food, and includes
      data generated using chromatographic and non-chromatographic methods of analysis.

PMID- 10895932
TI  - Determination of trenbolone and zeranol in bovine muscle and liver by liquid
      chromatography-electrospray mass spectrometry.
AB  - A sensitive and selective method using liquid chromatography (LC)-electrospray
      mass spectrometry for the determination of growth promoters, trenbolone and
      zeranol, in bovine muscle and liver has been developed. The LC separation was
      performed on a Zorbax XDB-C18 column (150x2.1 mm I.D.) using 0.005% acetic acid
      acetonitrile (60:40, v/v) as the mobile phase at a flow-rate of 0.2 ml/min. The
      positive ionization produced typical (M+H)+ molecular ions of alpha-trenbolone
      and beta-trenbolone. On the other hand, the negative mode produced (M-H)- ion of
      zeranol. The calibration graphs for alpha-trenbolone, beta-trenbolone and zeranol
      were rectilinear from 2.5 pg to 1.0 ng with selected ion monitoring. The drugs
      were extracted with 0.2% metaphosphoric acid-acetonitrile (6:4, v/v), and the
      extracts were cleaned up on a OASIS HLB (60 mg) cartridge. The recoveries of the
      hormones from bovine muscle fortified at 2 ng/g were 82.3-85.1%, and detection
      limits were 0.5 ng/g for each drug.

PMID- 10895933
TI  - Quantitation of nine quinolones in chicken tissues by high-performance liquid
      chromatography with fluorescence detection.
AB  - A simple reversed-phase high-performance liquid chromatographic method was
      developed and validated for simultaneous analysis of nine quinolones
      (ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, flumequine,
      marbofloxacin, nalidixic acid, oxolinic acid, sarafloxacin) in chicken tissue.
      The analytes were extracted from homogenized muscle using an acetonitrile basic
      solution. After centrifugation and partial evaporation, direct injection was
      possible. Three different HPLC conditions were applied to quantify the residual
      quinolones. Separation was achieved on a PLRP-S column and detection was
      performed with a monochromator fluorescence detector. The recovery, the limit of
      detection, the limit of quantification, the accuracy and the precision of the
      method were evaluated from spiked tissue samples at concentration levels ranging
      from 15 microg kg(-1) to 300 microg kg(-1) according to the maximum residue limit
      of each quinolone. This method is also suitable for porcine, bovine, ovine and
      fish muscle tissue.

PMID- 10895934
TI  - Determination of nicarbazin and clopidol in poultry feeds by liquid
      chromatography.
AB  - A rapid and very effective analytical procedure for the simultaneous liquid
      chromatographic determination of two coccidiostats, clopidol (CLOP) and
      nicarbazin (NICA), in poultry feeds was developed and tested. The ground feed
      samples were extracted using aqueous dimethylformamide after moistening with
      water. Co-extracted feed constituents were removed with a solid-phase extraction
      alumina-basic column and the eluates were directly analyzed on an ODS column
      (250x4.6 mm, 5 microm) with acetonitrile-0.01 M acetate buffer (pH 4.6) as
      eluent. UV detection of CLOP and the 4,4'-dinitrocarbanilide portion of NICA was
      carried out at 265 and 345 nm, respectively. The mean recovery from NICA spiked
      samples was 95% with a RSD of 4% in a concentration range of 2-150 mg/kg while
      for CLOP it was 98% with a RSD of 5% in a concentration range of 5-150 mg/kg. The
      limits of detection of NICA and CLOP in feed, based on a detector signal-to-noise
      ratio of 3, were estimated to be 1 mg/kg and 2.5 mg/kg, respectively, and the
      lowest levels tested in feeds by this procedure were 2 mg/kg and 5 mg/kg,
      respectively.

PMID- 10895935
TI  - Determination of clopidol residues in chicken tissues by high-performance liquid
      chromatography-mass spectrometry.
AB  - A high-performance liquid chromatographic-mass spectrometric (HPLC-MS) method has
      been developed for determination of clopidol residues in chicken tissues. Samples
      are extracted with acetonitrile. The extracts are cleaned up on an alumina column
      followed by an anion-exchange column. The clopidol is separated on a column (150
      cmx4.6 mm) of Intertsil by using acetonitrile-water (20:80) as mobile phase. The
      clopidol was qualitatively identified by molecule mass and determined
      quantitatively by selected ion monitoring mode at 190 m/z. The recoveries with
      RSDs ranged from 91.6+/-10.1 to 97.3+/-5.7 at 0.010 to 10.0 mg/kg by spiking
      three matrices (chicken muscle, liver, and kidney). The limit of detection was
      0.005 mg/kg, and the limit of quantification was 0.010 mg/kg.

PMID- 10895936
TI  - Determination of four nitroimidazole residues in poultry meat by liquid
      chromatography-mass spectrometry.
AB  - A multi-residue liquid chromatography-mass spectrometry (LC-MS) assay method is
      described for the determination of four nitroimidazoles in poultry muscle. The
      extraction procedure is based on liquid-liquid extraction with ethyl acetate
      followed by an evaporation step. A deuterated internal standard is used. The LC
      separation was made on a C18 bonded silica column with an aqueous formic acid
      (0.2%) solution-methanol-acetonitrile (81:13:6) mobile phase. Following
      electrospray ionization, the protonated molecular ion [M+H]+ is obtained for each
      compound. Monitoring several ions for each nitroimidazole provides the
      specificity required for confirmatory assay. Validation of the method was
      performed to estimate linearity, intra-day and inter-day repeatability, accuracy
      and detection limit. The present method is capable of identifying nitroimidazole
      residues in muscle at levels below 5 microg/kg.

PMID- 10895937
TI  - Simultaneous determination of triclabendazole and its sulphoxide and sulphone
      metabolites in bovine milk by high-performance liquid chromatography.
AB  - A simple method has been developed for the simultaneous determination of
      triclabendazole and its metabolites (sulphoxide and sulphone) in bovine milk by
      reversed-phase high-performance liquid chromatography (HPLC). A milk sample was
      homogenized with sodium sulfate anhydrous and acetonitrile, and centrifuged. The
      supernatant was isolated, rinsed with n-hexane saturated with acetonitrile, and
      evaporated. The residue was dissolved with 0.1 M potassium dihydrogenphosphate,
      and 0.1 M sodium hydrogencarbonate, and then cleaned up on a Bond Elut C18
      cartridge. The three compounds were separated on a Capcell Pak C18 UG 120 (5
      microm, 150x4.6 mm I.D.) column and determined by UV detection at 295 nm. The
      mobile phase was acetonitrile-0.05 M ammonium acetate (50:50), and the flow-rate
      was 0.8 ml/min at 40 degrees C. The mean recoveries (n=4) were 89.1-95.0% with a
      relative standard deviation of 1.1-2.6%. The detection limits were 0.004-0.006
      microg/g in milk. The proposed method was used to monitor raw milk samples for
      the market, and applied to the analysis of milk samples from 10 cows which had
      been administered with triclabendazole to control the liver fluke. The
      confirmation of the triclabendazole and its metabolites in the above milk sample
      has been achieved by electrospray LC-MS for the first time.

PMID- 10895938
TI  - Chromatographic analysis of tetracycline antibiotics in foods.
AB  - Tetracycline antibiotics (TCs), such as oxytetracycline, tetracycline,
      chlortetracycline, and doxycycline, have for decades continued to play an
      important role in veterinary medicine and feed additives because of the broad
      spectrum antibiotics and their economical advantages. Many analysis methods of
      TCs, therefore, have been reported to monitor their residues in foods. We review
      the recent developments in chromatographic analysis methods for TCs in foods.
      This review involves the following techniques: thin layer chromatography,
      capillary electrophoresis, high-performance liquid chromatography, and sample
      preparation including extraction and clean up procedures.

PMID- 10895939
TI  - Stability of penicillin antibiotic residues in meat during storage. Ampicillin.
AB  - Incurred samples from a pig treated with ampicillin, one of the most important
      penicillin antibiotic drugs used in food-producing animal treatments, were
      analyzed at the residue level of the drug in muscle tissue (approximately 100
      microg kg(-1)) during their freezing storage and using three different
      techniques: quantitative microbiological assay, HPLC-UV and LC-MS. Two parameters
      have been specifically monitored: storage temperature (-20 and -75 degrees C) and
      storage packaging (ground meat or bulk meat). No significant decrease was
      observed during the first 3 months of storage monitoring at -20 and -75 degrees
      C. On the contrary, the sample preparation significantly affected the drug
      concentration in muscle from the very beginning of the storage. Grinding the meat
      before storage allowed to keep the drug near the higher level of concentration
      (approximately 100 microg kg(-1)) when bulk meat stored frozen systematically led
      to a decreased value (approximately 75 microg kg(-1)). After 8 months of storage
      at -20 degrees C, a significant decrease arose and was never observed at -75
      degrees C. All the results were similarly obtained with the three different
      techniques used simultaneously, which allows to indicate a good correlation
      between the techniques.

PMID- 10895940
TI  - Determination of cephalosporins in raw bovine milk by high-performance liquid
      chromatography.
AB  - A high-performance liquid chromatographic (HPLC) method based on solid-phase
      extraction was developed for the determination of cefazolin, cefoperazone,
      cefquinome and ceftiofur in raw bovine milk. The milk fat was removed by
      centrifugation and the cephalosporins were extracted in acetonitrile. The extract
      was cleaned up by solid-phase extraction on an octadecyl sorbent. The compounds
      were separated by ion-paired gradient HPLC on a phenyl column with ultraviolet
      detection at 270 nm. The limits of detection estimated by a conservative model
      were 11 microg/kg for cefazolin and cefoperazone and 7 microg/kg for cequinome
      and ceftiofur. The mean recoveries were 86-88% for cefazolin, 91-93% for
      cefoperazone, 69-72% for cefquinome and 84-88% for ceftiofur in the concentration
      range 20-200 microg/kg.

PMID- 10895941
TI  - Pesticide residue determination in fruit and vegetables by liquid chromatography
      mass spectrometry.
AB  - An overview is given of pesticide residue determination in fruit and vegetables
      by liquid chromatography-mass spectrometry (LC-MS). Emphasis is placed on the
      thermospray, particle beam and atmospheric pressure ionization interfaces
      including advantages and drawbacks and typical detection limits. The capacity of
      each interface to provide useful data for identification/confirmation of analytes
      and the possibility of obtaining structural information for the identification of
      target and non-target compounds is discussed. Finally, sample preparation
      techniques are dealt with in relation to their influence on further LC-MS
      determination.

PMID- 10895942
TI  - Analysis of herbicide residues in cereals, fruits and vegetables.
AB  - The determination of herbicide residues in cereals, fruits and vegetables by
      chromatographic methods is reviewed. The principal chemical groups of herbicides,
      like phenoxyacids, benzonitriles, ureas, triazines, dinitroanilines,
      chloroacetamides, carbamates, uracils, glyphosate and bipyridylium compounds, are
      considered. This review briefly provides some basic information on food sample
      extraction, clean-up, derivatization and determination of herbicide residues.

PMID- 10895943
TI  - Simplified method for the determination of chlorinated fungicides and
      insecticides in fruits by gas chromatography.
AB  - A fast, reliable method for the determination of more than twenty chlorinated
      fungicides and insecticides in a variety of fruit samples is presented. The
      pesticides are extracted from chopped samples with magnetic stirring, after
      adding 13 ml of acetone-phosphate buffer-brine solution (12:1, v/v) with 5 ml of
      n-hexane. The continuous module employed allows sequential decolourization of the
      organic phase, solvent changeover and solid-phase extraction for clean-up and
      preconcentration purposes. A 1-microl aliquot of the pesticides in ethyl acetate
      (eluent) is finally injected into the gas chromatograph for separation and
      identification. The method provides excellent clean-up despite the complexity of
      the matrices involved. Fruit samples (5-20 g) containing 0.1-1250 ng/g pesticides
      were analysed with a high precision (4-6%). After contamination of the fruit
      samples for 12 h, average recoveries >90% at fortification levels of 5-25 ng/g
      were obtained for most of the pesticides. Positive findings of these pesticides
      in fruits purchased at local markets were confirmed by GC-MS.

PMID- 10895944
TI  - Multiresidue analysis of seventeen pesticides in wine by gas chromatography with
      mass-selective detection.
AB  - We have developed a multiresidue method permitting the simultaneous quantitation
      of 17 pesticides in wine: dicloran, dimethoate, diazinon, chlorpyrifos-methyl,
      vinclozolin, carbaryl, methiocarb, dichlofluanid, parathion-ethyl, triadimefon,
      procymidone, myclobutanil, iprodione, imidan, dicofol, phosalone and azinphos
      methyl. Solid-phase extraction of 0.5 ml of wine sample is followed by direct
      injection of 1 microl of the eluent onto a DB-5 MS gas chromatographic column
      followed by mass-selective detection using one target and two qualifier ions for
      each pesticide. The extraction and injection steps are carried out with automatic
      instrumentation. Good resolution of all compounds was achieved with a run-time
      approximating 23 min. Detection and quantitation limits were around 2 microg/l
      and 10 microg/l, respectively, with linear calibration curves up to 3 mg/l for
      most constituents. Recovery in half the compounds was >90%, and >80% in most of
      the remainder. Imprecision (relative standard deviation) was <10% for most
      pesticides and <18% in all. Further analytes can be added to the repertoire
      without difficulty. The method merits consideration together with four other
      multiresidue methods now available that offer similar analytical characteristics,
      slower run-times, and a different selection of analytes.

PMID- 10895945
TI  - Multiresidue method for the rapid determination of organophosphorus insecticides
      in grapes, must and wine.
AB  - A rapid multiresidue gas chromatographic method for determining 12 insecticides
      in grapes, must and wine is described. A simple on-line microextraction method
      for isolating frequently applied insecticides on vineyard is used. The matrix,
      once extracted with an acetone-dichloromethane (1:1, v/v) mixture, was filtered
      and concentrated. Nitrogen-phosphorus detection (NPD) and electron-capture
      detection (ECD) were used to identify and quantify the insecticides, the findings
      being confirmed using mass spectrometric detection (MSD). No clean-up was
      necessary for either NPD or ECD. The regression coefficients relating to
      linearity were at least 0.99. Recoveries from spiked grape, must and wine samples
      ranged from 80 to 108% and relative standard deviations were no higher than 16%
      in the most unfavourable case. Individual detection limits were in the range 0.02
      0.1 ng. Limits of quantification varied from 0.01 to 0.05 mg kg(-1), which are
      below the maximum residue limits set by the legislation of the main wine
      producing countries of the European Union. Only in the case of methidathion and
      quinalphos were the limits of quantification equivalent to the maximum residue
      limits (0.05 mg kg(-1)) established by Spanish and French legislation,
      respectively.

PMID- 10895946
TI  - Multiresidue method for the rapid determination--in grape, must and wine--of
      fungicides frequently used on vineyards.
AB  - A rapid multiresidue gas chromatographic method for determining 17 fungicides in
      grapes, must and wine, widely used on vineyards, is described. A simple on-line
      microextraction method for isolation of fungicides was used. Nitrogen-phosphorus
      and electron-capture detection were used for the identification and quantitation
      of pesticides. For confirmation, mass spectrometic detection was used. Because of
      the high selectivity of both detection methods, no clean-up was necessary. The
      regression coefficients relating to linearity were at least 0.994. Recoveries
      from spiked grapes, must and wine samples ranged from 78 to 107% and relative
      standard deviations were not higher than 14%. Individual detection limits were in
      the range 0.02-0.1 ng. Limits of quantification varied from 0.01 to 0.05 mg/kg,
      smaller in all cases than the maximum residue limits set down by the legislations
      of Spain, France and Italy, the main wine-producing countries of the European
      Union. Only for fludioxonil and hexaconazole do the limits of quantification
      coincide with the maximum residue limits (0.05 mg/kg) established by the Spanish
      legislation.

PMID- 10895947
TI  - Interlaboratory study of identification and quantitation of multiresidue
      pyrethroids in agricultural products by gas chromatography-mass spectrometry.
AB  - This paper deals with the different GC-MS analytical conditions adopted by four
      laboratories in an attempt to confirm the accuracy of the GC-electron-capture
      detection (ECD) analytical results during the international collaborative study
      for the establishment of the AOAC Official Method 998. 01. What is especially
      noted is that two laboratories have conducted comparative analysis of the
      respective 12 blind samples with both methods of GC-ECD and GC-MS, and the
      analytical results of the two methods turn out to be basically identical. This
      fully demonstrates that GC-MS is not only an effective confirmation tool in the
      analysis of the pyrethroid residues but also of sufficient sensitivity regarding
      the maximum residue limit of determination prescribed by FAO/WHO. Moreover, its
      selectivity is better than GC-ECD.

PMID- 10895948
TI  - Gas chromatographic determination of acrinathrine and 3-phenoxybenzaldehyde
      residues in honey.
AB  - A procedure involving an extraction step and further gas chromatographic analysis
      with flame ionization detection to determine residues of acrinathrine and its
      main metabolite, 3-phenoxybenzaldehyde, in honey is proposed. Residues can be
      isolated from the matrix by means of liquid-liquid extraction with a mixture of
      benzene-isopropanol, by solid-phase extraction with octadecylsilane cartridges or
      Florisil packed columns, the latter method giving higher recoveries. Assays on
      spiked honey samples are carried out to test the procedures that are afterwards
      applied to honey samples from treated beehives.

PMID- 10895949
TI  - Polycyclic aromatic hydrocarbons in edible fats and oils: occurrence and
      analytical methods.
AB  - This review deals with analytical methods for polycyclic aromatic hydrocarbon
      (PAH) determination in oils and fats. The data reported in the introduction deal
      with PAH dietary intake from this group of food and contamination levels recently
      found by some authors in different vegetable oils, stressing the importance of
      establishing a method suitable for routine analyses. Traditional sample
      preparation relies on tedious, time-consuming procedures. They generally consist
      of an extraction step (liquid-liquid partition, caffeine complexation,
      saponification) followed by one or more purification procedures (column
      chromatography, thin-layer chromatography, solid-phase extraction). The
      analytical determination is usually carried out by HPLC and spectrofluorometric
      detection, or through high-resolution capillary GC coupled to flame ionisation
      detection or mass spectrometry. LC is a valid alternative to the traditional
      sample preparation, and off-line LC-LC allows performing an accurate PAH analysis
      in less than 2 h. Also supercritical fluid extraction, allowing performing both
      extraction and clean-up in one combined step, is a promising technique.
      Hyphenated techniques such as LC-GC and LC-LC-GC seem to be very promising. A
      completely on-line method for alkylated PAH determination in oils or lipidic
      extracts contaminated with mineral oil involves a two-dimensional LC-step with
      intermediate eluent evaporation and GC transfer through a vaporiser/overflow
      interface.

PMID- 10895950
TI  - Contamination in food from packaging material.
AB  - Packaging has become an indispensible element in the food manufacturing process,
      and different types of additives, such as antioxidants, stabilizers, lubricants,
      anti-static and anti-blocking agents, have also been developed to improve the
      performance of polymeric packaging materials. Recently the packaging has been
      found to represent a source of contamination itself through the migration of
      substances from the packaging into food. Various analytical methods have been
      developed to analyze the migrants in the foodstuff, and migration evaluation
      procedures based on theoretical prediction of migration from plastic food contact
      material were also introduced recently. In this paper, the regulatory control,
      analytical methodology, factors affecting the migration and migration evaluation
      are reviewed.

PMID- 10895951
TI  - Determination of synthetic phenolic antioxidants in food by high-performance
      liquid chromatography.
AB  - This review deals with HPLC method to be used for the determination of synthetic
      phenolic antioxidants added to various foods. Sample preparation, isolation
      techniques, separation systems as well as detection methods used in applied food
      analysis procedures are discussed.

PMID- 10895952
TI  - Application of chromatographic and electrophoretic methodology to the speciation
      of organomercury compounds in food analysis.
AB  - Trace metals such as mercury, especially its organic compounds, are an important
      risk to the environment and to man due to their accumulation in the food chain.
      For this reason, the routine determination of the very toxic methylmercury, and
      of other organic and inorganic mercury compounds in marine and land animals,
      vegetables, fruits and fresh water is of increasing importance in health and
      environmental control programmes throughout the world. The majority of speciation
      methods for organomercurials involve a series of fundamental steps for the
      identification and quantification of samples of biological origin: extraction or
      isolation from the matrix; derivatisation and concentration; detection;
      separation of different species of interest and of interference. Each of these
      steps, as part of the chromatographic analysis of MeHg and of other
      organomercurials is revised in this study using food samples.

PMID- 10895953
TI  - Eliminating the chlorite interference in US Environmental Protection Agency
      Method 317.0 permits analysis of trace bromate levels in all drinking water
      matrices.
AB  - A post-column reagent (PCR) method for bromate analysis in drinking water with a
      method detection limit (MDL) and method reporting limit (MRL) of 0.1 and 0.5
      microg/l, respectively, has been developed by the United States Environmental
      Protection Agency (EPA) for future publication as EPA Method 317.0. The PCR
      method provides comparable results to the EPA's Selective Anion Concentration
      (SAC) method used to support the laboratory analysis of Information Collection
      Rule (ICR) low-level bromate samples and offers a simple, rugged, direct
      injection method with potential to be utilized as a compliance monitoring
      technique for all inorganic Disinfectants/Disinfection By-Products (D/DBPs). It
      has superior sensitivity for bromate compared to EPA Method 300.1, which was
      promulgated as the compliance monitoring method for bromate under Stage 1 of the
      D/DBP rule. This paper addresses elimination of the chlorite interference that
      was previously reported in finished waters from public water systems (PWSs) that
      employ chlorine dioxide as the disinfectant. An evaluation of Method 317.0 for
      the analysis of bromate in commercial bottled waters is also reported.

PMID- 10895954
TI  - On-line microdialysis-ion chromatographic determination of inorganic anions in
      olive-oil mill wastewater.
AB  - A fully automated method is presented for the determination of inorganic anions
      in olive-oil mill effluents using on-line dialysis-ion chromatography. The
      wastewater is first of all sonicated at room temperature to make it homogeneous,
      then diluted and microdialized. Most of the organic load of the effluents is
      removed in a few minutes without using reagents, while soluble anion quantitation
      remains unaffected. The clear solution is analyzed for the inorganic anions
      content by direct injection on to an ion chromatograph equipped with a
      conductivity detector. In the absence of standards, the separation efficiency of
      microdialysis has been investigated by spiking wastewater samples as well as
      standard oil emulsions with varying amounts of inorganic anions and subjecting
      them to microdialysis for different periods of time prior to performing
      instrumental analysis. Excellent spike recoveries and low relative standard
      deviations are obtained for all the anions if a 10 min microdialysis time is
      overcame. Chloride, nitrite, nitrate, phosphate and sulphate are not affected by
      the microdialysis procedure and their recovery is between 96 and 104% in
      wastewater as well as in standard oil emulsion. Calibration plots are linear over
      about two orders of magnitude. The dialysis membrane has been replaced after more
      than 100 analyses. The UV photolysis pre-treatment of the same sample evidences
      the different information that can be obtained by the two sample pre-treatment
      procedures.

PMID- 10895955
TI  - Monitoring and control of industrial downstream processing of sugar beet
      molasses.
AB  - In present work the determination of several amino acids during the industrial
      chromatographic desugarisation of molasses is presented. The use of innovative
      biosensor systems for highly specific detection of serine is described. Using two
      dimensional fluorescence spectrometry, a non-invasive method for the
      determination of several product fractions could be established in an industrial
      chromatographic procedure.

PMID- 10895964
TI  - The role of cytokines in rhinosinusitis.
AB  - Since the last decade, new insights into inflammatory processes have become
      possible by investigating the pattern of cytokines in acute and chronic sinus
      diseases. This review aims to update and discuss the findings of in vitro and in
      vivo studies concerning the role of cytokines in sinusitis and nasal polyposis.
      The proinflammatory cytokines interleukin-1beta, interleukin-6 and the neutrophil
      chemoattractant interleukin-8 may play a major role in acute sinusitis, as shown
      in viral and allergic rhinitis. In chronic sinusitis interleukin-3 dominates the
      cytokine profiles, giving support to a variety of inflammatory cells. Interleukin
      5 is a key protein in the pathogenesis of nasal polyposis. Activation and
      survival of eosinophils in nasal polyps are thought to be regulated by
      interleukin-5. Further investigation of cytokine expression patterns in
      inflammatory sinus diseases will lead to a better understanding of their
      pathogenesis and to a development of new therapeutic modality.

PMID- 10895965
TI  - Clinical correlations of peripheral blood microchimerism after liver
      transplantation.
AB  - The aim of this study was to evaluate microchimerism after human liver
      transplantation (LT). This study included 13 female recipients who received
      hepatic allograft from male donors at Asan Medical Center. A nested PCR specific
      for Y-chromosome gene (DYZ3) was used to analyze the small number of male cells
      in the peripheral blood mononuclear cells of the female recipients.
      Microchimerism was observed in 6 of 13 recipients and 16 out of 35 samples. Only
      3 patients showed microchimerism 3 months after LT. There was no statistical
      difference between the presence of microchimerism and clinical findings such as
      type of donor, type of immunosuppression, episode of rejection and age of
      recipient. This study did not show any clinical relevance of microchimerism and
      further larger study are needed to confirm the results.

PMID- 10895966
TI  - BCG infection during pre-sensitization or even post-sensitization inhibits airway
      sensitivity in an animal model of allergic asthma.
AB  - The objective of this study is to investigate whether BCG infection before,
      during or after sensitization suppresses allergen-induced airway
      hyperresponsiveness and eosinophilic inflammation in allergic asthma rats, and to
      determine the required dose of BCG to induce such an inhibition. Eighty-seven
      Sprague-Dawley (SD) rats were sensitized and provoked with ovalbumin (OA). A
      pretreatment of 6 x 10(4) or 6 x 10(5) colony forming units (CFUs) of BCG or
      saline was done at four different times: 3 days before sensitization, at
      sensitization, 3 days before provocation, or at provocation. The assessment of
      tracheal smooth muscle (TSM) responsiveness to electrical field stimulation or
      acetylcholine (ACh) and bronchoalveolar lavage (BAL) were performed 1 day after
      OA provocation. Doses of 6 x 10(4) CFUs inhibited TSM sensitivity of rats
      infected 3 days before sensitization or at sensitization, but not 3 days before
      provocation or at provocation. However, doses of 6 x 10(5) CFUs significantly
      inhibited not only the airway eosinophilia of rats infected 3 days before
      sensitization or at sensitization, but also the TSM sensitivity of rats infected
      3 days before provocation or at provocation. In conclusion, BCG infection
      suppresses the development of sensitivity of airway smooth muscle and airway
      eosinophilic inflammation in allergic asthma rats. Furthermore, a relatively high
      dose of BCG infection inhibits airway sensitivity, even after allergen
      sensitization.

PMID- 10895967
TI  - Activated platelets induce secretion of interleukin-1beta, monocyte chemotactic
      protein-1, and macrophage inflammatory protein-1alpha and surface expression of
      intercellular adhesion molecule-1 on cultured endothelial cells.
AB  - Atherosclerosis is an inflammatory disease. Platelet-endothelium interaction
      plays an important role in the pathophysiology of atherogenesis. We investigated
      the role of activated platelets for secretion of interleukin (IL)-1beta, monocyte
      chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha and
      expression of intercellular adhesion molecule (ICAM)-1 on endothelial cells.
      Human umbilical vein endothelial cells (HUVEC) were incubated with non-stimulated
      or ADP-activated platelets for 6 hr. Secretion of interleukin (IL)-1beta, MCP-1
      and MIP-1alpha and surface expression of ICAM-1 were measured by ELISA and flow
      cytometry. In the presence of activated platelets, the secretion of IL-1beta, MCP
      1, and MIP-1alpha and surface expression of ICAM-1 were significantly increased
      compared with non-activated platelets. The present study shows that activated
      platelets may contribute to expression of various inflammatory mediators on
      endothelial cells.

PMID- 10895968
TI  - Vascular endothelial growth factor in malignant and tuberculous pleural
      effusions.
AB  - The purpose of this study is to assess the usefulness of soluble vascular
      endothelial growth factor (VEGF) in the effusions of patients with malignant and
      tuberculous diseases. Using a sandwich enzyme-linked immunoadsorbent assay, VEGF
      concentration was measured in malignant (n=17) and tuberculous (n=11) pleural
      effusions. Pleural biopsy, cytology or microbiological methods were used to make
      final diagnoses. Adenosine deaminase (ADA) levels in tuberculous pleural
      effusions were significantly higher than those in malignant pleural effusions.
      The median level of VEGF in patients with malignant effusions (median, 2418
      pg/mL; range, 97-62103 pg/mL) was significantly higher than tuberculous effusions
      (median, 994 pg/mL; range, 44-3552 pg/mL). There were no significant differences
      in pleural VEGF levels in patients with different histological types of lung
      cancer. The VEGF level was not correlated with ADA, lactate dehydrogenase and
      total protein levels of pleural fluid. In conclusion, pleural VEGF levels in
      patients with malignant effusions were significantly higher than tuberculous
      effusions, and the measurement of pleural VEGF is helpful in discriminating
      between malignant and tuberculous effusions. Further studies are needed to
      determine the clinical value of VEGF as a tumor marker and a prognostic factor.

PMID- 10895969
TI  - Abnormalities of erythrocyte membrane proteins in Korean patients with hereditary
      spherocytosis.
AB  - Hereditary spherocytosis (HS) is a common inherited erythrocyte membrane disorder
      characterized by chronic hemolytic anemia. Clinical manifestations and
      biochemical abnormalities of HS are heterogeneous. In this study, we investigated
      erythrocyte membrane protein defects in 27 Korean HS cases. Utilizing both the
      Fairbanks system and the Laemmli system, sodium dodecyl sulfate polyacrylamide
      gel electrophoresis of erythrocyte membrane proteins was performed. Proteins were
      stained with Coomassie brilliant blue and gels were scanned using a densitometer.
      We detected spectrin deficiency in 7.4% of cases (2/27), ankyrin deficiency in
      29.6% (8/27), combined spectrin and ankyrin deficiency in 3.7% (1/27), band 3
      deficiency in 11.1% (3/27) and protein 4.2 deficiency in 14.8% (4/27). Membrane
      protein deficiencies were not observed in nine cases (33.3%, 9/27). Members of
      two of seven families tested showed the same protein defects as the proband.
      Ankyrin deficiency alone and combined with spectrin deficiency accounted for
      33.3% of cases (9/27), and they were the most common biochemical defects in
      Korean HS cases. Protein 4.2 deficiency caused HS more frequently in Koreans than
      in Caucasians.

PMID- 10895970
TI  - Genetic variation of the Apo Al-CIII-AIV gene cluster in hypertriglyceridemic
      patients with chronic renal failure undergoing hemodialysis.
AB  - Many patients with chronic renal failure (CRF) requiring hemodialysis present
      with hypertriglyceridemia (HTG). But the exact cause of HTG in CRF is still
      unknown. Genetic variation of the apo AI-CIII-AIV gene cluster was reported to be
      associated with primary HTG, atherosclerosis and coronary artery disease. This
      study was designed to evaluate the association between the restriction fragment
      length polymorphism (RFLP) of the apo AI-CIII-AIV gene cluster and HTG in
      patients with CRF undergoing hemodialysis. Genetic variations of the apo AI-CIII
      AIV gene cluster were analysed in peripheral leukocyte samples from 59 patients
      with CRF undergoing hemodialysis: 17 patients with HTG (CRF-HTG) and 42 patients
      without HTG (CRF-NTG). The RFLP was achieved through the digestion of PCR
      products by two restriction enzymes, SstI and MspI. The frequency of SstI minor
      allele (S2) in CRF-HTG was 0.44, which was significantly higher than that in CRF
      NTG (0.17). Frequencies of MspI minor allele (M2) in CRF-HTG and CRF-NTG were not
      significantly different (0.5 vs 0.32) (p=0.07). Frequencies of S2-M2 genotype
      were 0.65 in CRF-HTG, and 0.27 in CRF-NTG (p<0.005). These data indicate that
      genetic variation of the apo AI-CIII-AIV gene cluster may serve as one of the
      causes of HTG in CRF.

PMID- 10895972
TI  - The effect of oxytocin antagonist on uterus in response to exogenous oxytocin.
AB  - This study was performed to determine the action mode of oxytocin antagonist. In
      Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was
      examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr.
      Uterine activities were monitored with a polygraph. Study 2 determined the effect
      of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI
      treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study
      1, the uterine contractile response to oxytocin was significantly inhibited
      (p<0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No
      differences in response were detected compared to controls (p>0.05) at later
      hours. In Study 2, no differences (p>0.05) between the AI and control animals in
      either oxytocin receptor number or binding affinity was found. These data suggest
      that the major mode of AI action is via competitive inhibition at the uterine
      oxytocin receptor and not by altering receptor number or binding affinity. AI is
      suggested to have the potential of being a potent and specific tocolytic agent
      for prevention of preterm labor in human.

PMID- 10895971
TI  - Effects of acetaldehyde on responses of rabbit corpus cavernosal smooth muscle.
AB  - Ethanol has various effects on male sexual activity under the influence of direct
      and indirect, in acute and chronic alcohol ingestion. However, whether
      acetaldehyde, a principal metabolite of ethanol, may affect penile erection
      directly has still not been elucidated. This present study was, therefore,
      designed to clarify the pharmacologic effects of the acetaldehyde on corpus
      cavernosal smooth muscle. Corpus cavernosal strips were prepared from rabbit
      penises. Isometric tension changes of rabbit corpus cavernosal strips to various
      drugs and electrical field stimulation (EFS) in an organ chamber were recorded
      with a pressure transducer after active muscle tone had been induced by
      phenylephrine (10(-5) mol/L). At the concentrations employed, acetaldehyde had no
      effect on the pH of the bathing medium. Acetaldehyde in each concentration did
      not significantly affect resting tone of the smooth muscle during 30 min
      incubation. Acetaldehyde suppressed contractility induced by phenylephrine and
      KCI at 10(-4) mol/L, and relaxation induced by EFS and bethanechol at 10(-3)
      mol/L and 10(-4) mol/L respectively, but acetaldehyde enhanced relaxation induced
      by ATP at high acetaldehyde level. Sodium nitroprusside-induced relaxation was
      not affected at any employed acetaldehyde concentration. This suggests that
      increasing the acetaldehyde level may contribute to male erectile dysfunction
      mainly by the inhibition of nitric oxide formation.

PMID- 10895973
TI  - FES-biofeedback versus intensive pelvic floor muscle exercise for the prevention
      and treatment of genuine stress incontinence.
AB  - We undertook this work to compare the treatment efficacies and the changes of
      quality of life after pelvic floor muscle (PFM) exercise and the functional
      electrical stimulation (FES)-biofeedback treatment, both of which are being
      widely used as conservative treatment methods for female urinary incontinence. We
      randomly selected 60 female incontinence patients who visited our department and
      divided them evenly into two groups. They were treated for a period of 6 weeks.
      The subjective changes in the severity of incontinence and discomfort in daily
      and social life were measured using a translated version of the questionnaire by
      Jackson. Objective changes of pelvic muscle contraction force were measured using
      a perineometer. Pre- and post-treatment maximal pelvic floor muscle contractile
      (PMC) pressure and changes in the severity of urinary incontinence and discomfort
      of the two groups showed statistically significant differences (p<0.001). In
      particular the FES-biofeedback group showed significantly increased maximal PMC
      pressure and a decreased severity of urinary incontinence and discomfort compared
      to the intensive PFM exercise group (p<0.001). In conclusion, FES-biofeedback
      proved more effective than simple PFM exercise.

PMID- 10895974
TI  - Matrix metalloproteinases in human gliomas: activation of matrix
      metalloproteinase-2 (MMP-2) may be correlated with membrane-type-1 matrix
      metalloproteinase (MT1-MMP) expression.
AB  - To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue
      inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix
      metalloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these
      proteins were investigated in ten cases of human glioma and two meningioma
      tissues and eight human glioma cell lines. In gelatin zymography, MMP-2
      activities of glioblastomas were higher than astrocytomas. The activated form of
      MMP-2 was seen in five of six cases of glioblastomas, but not in astrocytomas.
      MMP-9 activity was detected in all cases of malignant astrocytomas but the
      reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expression in
      glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas
      with activated form of MMP-2 had MT1-MMP expressions. In vitro, human glioma cell
      lines with high expression of MT1-MMP also showed high MMP-2 activity. TIMP-1
      transcripts were constitutively present in almost all glioma tissues and cell
      lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance
      of TIMP-2/MMP-2 was observed using immunoprecipitation analysis in a glioma cell
      line. High expression of MMP-2 and MT1-MMP is possibly involved in invasiveness
      of malignant glioma.

PMID- 10895975
TI  - Potentials and limitations of adenovirus-p53 gene therapy for brain tumors.
AB  - We investigated the antineoplastic potentials of recombinant adenovirus
      containing wild-type p53 cDNA (Ad5CMV-p53) for malignant gliomas. In four human
      glioma cell lines (U-251 and LG expressing endogenous mutant p53, and U-87 and
      EFC-2 expressing wild-type p53) and two rat glioma cell lines (9L and C6, each
      expressing mutant and wild-type p53), gene transfer efficiency determined by X
      gal staining and Western blotting was varied (10-99% at 10-500 multiplicity of
      infection, MOI). Growth inhibitory effect was drastic (>90% at 100 MOI) in U-251
      cells and only moderate or minimal in other cell lines harboring wild-type p53 or
      low gene transfer efficiency. Ex vivo transduction of U-251 cells with Ad5CMV-p53
      suppressed the in vivo tumorigenicity of the cells. Histopathologic examination
      for Ad5CMV-p53 toxicity to rat brains showed inflammatory reactions in half of
      the tested brains at 10(8) MOI. U-251 cells were inoculated intracerebrally in
      nude mice and injected Ad5CMV-p53 into the tumor, in which neither the tumor
      suppression nor the survival benefit was observed. In conclusion, heterogeneity
      of the cellular subpopulations of malignant glioma in p53 status, variable and
      insufficient gene delivery to tumor, and adenoviral toxicity to brain at higher
      doses may be limiting factors to be solved in developing adenovirus-p53 gene
      therapy for malignant gliomas.

PMID- 10895976
TI  - Effects of oncostatin M on hormone release of rat pituitary cells in primary
      culture.
AB  - It has become increasingly clear that cytokines play an important role in
      modulating neuroendocrine regulation, especially in the secretion of
      corticotropin (ACTH) in the pituitary. Oncostatin M (OSM), a cytokine of IL-6
      family has been reported to increase ACTH secretion and pro-opiomelanocortin
      (POMC) transcription in murine corticotroph pituitary tumor cells (AtT20 cells).
      The present study was undertaken to determine the effects of OSM on hormonal
      release in primary culture of rat pituitary cells. Growth hormone or prolactin
      release was not affected by OSM. OSM (1 nM) stimulated ACTH release (35.1%
      increase versus control, p<0.001) in dispersed pituitary cells of rat to a lesser
      extent than in AtT20 cells. Corticotropin releasing hormone (CRH) (10 nM) also
      induced a 2.3-fold increase of ACTH secretion (p<0.001), but co-treatment of OSM
      and CRH did not exhibit any synergistic effect on ACTH secretion. We conclude OSM
      has a stimulatory effect on ACTH secretion in normal rat pituitary cell cultures,
      and OSM acts mainly on corticotroph, supporting the potential role of OSM to
      modulate immune-endocrine regulation in the pituitary.

PMID- 10895978
TI  - Congenital cytomegalovirus infection: three autopsy case reports.
AB  - We report three autopsy cases of congenital cytomegalovirus (CMV) infection in
      fetuses with a review of literature. The clinical manifestations in these cases
      of congenital CMV infection include intrauterine fetal death, hydrops fetalis,
      and CMV pneumonia associated with cardiovascular defect. The pathological
      characteristics were as follows: 1) the kidney was the most frequently involved
      organ, followed by lung and liver, 2) CMV inclusions were found predominantly in
      epithelial cells and to a lesser degree in endothelial cells, 3) intrahepatic
      bile duct epithelial cells were frequently involved, and 4) inflammatory reaction
      around CMV inclusions was not prominent in the early stage of pregnancy.
      Diagnostic confirmation was obtained by in situ hybridization (ISH) using a
      biotinylated CMV-DNA probe, which demonstrated intranuclear inclusions and
      sometimes recognized cells that did not show intranuclear inclusion.

PMID- 10895977
TI  - Anti-oxidative neuroprotection by estrogens in mouse cortical cultures.
AB  - Estrogen replacement therapy in postmenopausal women may reduce the risk of
      Alzheimer's disease, possibly by ameliorating neuronal degeneration. In the
      present study, we examined the neuroprotective spectrum of estrogen against
      excitotoxicity, oxidative stress, and serum-deprivation-induced apoptosis of
      neurons in mouse cortical cultures. 17beta-estradiol as well as 17alpha-estradiol
      and estrone attenuated oxidative neuronal death induced by 24 hr exposure to 100
      microM FeCl2, excitotoxic neuronal death induced by 24 hr of exposure to 30
      microM N-methyl-D-aspartate (NMDA) and serum-deprivation induced neuronal
      apoptosis. Furthermore, estradiol attenuated neuronal death induced by Abeta25
      35. However, all these neuroprotective effects were mediated by the anti
      oxidative action of estrogens. When oxidative stress was blocked by an
      antioxidant trolox, estrogens did not show any additional protection. Addition of
      a specific estrogen receptor antagonist ICI182,780 did not reverse the protection
      offered by estrogens. These findings suggest that high concentrations of estrogen
      protect against various neuronal injuries mainly by its anti-oxidative effects as
      previously shown by Behl et al. Our results do not support the view that
      classical estrogen receptors mediate neuroprotection.

PMID- 10895979
TI  - Acute respiratory distress syndrome associated with scrub typhus: diffuse
      alveolar damage without pulmonary vasculitis.
AB  - Pathologic findings of scrub typhus have been characterized by vasculitis of the
      microvasculature of the involved organ resulting from a direct invasion by
      Orientia tsutsugamushi. We experienced a case of acute respiratory distress
      syndrome (ARDS) associated with scrub typhus. The case was proven by eschar and
      high titer of serum IgM antibody (positive at 1:1280). Open lung biopsy showed
      diffuse alveolar damage (DAD) in the organizing stage without evidence of
      vasculitis. Immunofluorescent antibody staining and polymerase chain reaction for
      O. tsutsugamushi failed to demonstrate the organism in the lung tissue. The
      patient expired due to progressive respiratory failure despite doxycycline
      therapy. Immunologic mechanism, without direct invasion of the organism, may
      participate in the pathogenesis of ARDS associated with scrub typhus.

PMID- 10895980
TI  - Eosinophilic fasciitis preceding relapse of peripheral T-cell lymphoma.
AB  - Although eosinophilic fasciitis (EF) may precede hematologic malignancy or
      Hodgkin's disease, association with peripheral T-cell lymphoma (PTCL) is
      extremely rare. Only four cases of EF preceding or concomitant PTCL have been
      reported in the world literature. We experienced the first Korean case of EF
      complicated by the later relapse of peripheral T-cell lymphoma. A 63-year-old
      Korean male has been followed at our outpatient clinic periodically after
      treatment for stage IV PTCL. He had been in complete remission for seven and a
      half years when he developed edema of both lower extremities followed by
      sclerodermatous skin change in both hands with peripheral eosinophilia. Biopsy
      from the left hand showed fibrous thickening of the fascia with lymphoplasmacytic
      and eosinophilic infiltrate, consistent with EF. Twenty-five months later, a
      newly developed lymph node from the left neck showed recurrence of PTCL. EF may
      occur as a paraneoplastic syndrome associated with the relapse of PTCL.
      Therefore, in a patient with EF, the possibility of coexisting and/or future
      occurrence of hematologic neoplasm should be considered.

PMID- 10895981
TI  - Hepatic and small bowel mucormycosis after chemotherapy in a patient with acute
      lymphocytic leukemia.
AB  - Mucormycosis is a rare but invasive opportunistic fungal infection with increased
      frequency during chemotherapy-induced neutropenia. The clinical infections due to
      Mucor include rhinocerebral, pulmonary, cutaneous, gastrointestinal and
      disseminated diseases. The first two are the most common diseases and all
      entities are associated with a high mortality rate. Still hepatic involvement of
      Mucor is rarely reported. We experienced a case of hepatic and small bowel
      mucormycosis in a 56-year-old woman after induction chemotherapy for B-cell acute
      lymphocytic leukemia. Initial symptoms were a high fever unresponsive to broad
      spectrum antibiotics and pain in the left lower abdominal quadrant. It was
      followed by septic shock, deterioration of icterus and progressively elevated
      transaminase. An abdominal CT demonstrated multiple hypodense lesions with
      distinct margins in both lobes of liver and pericolic infiltration at small bowel
      and ascending colon. Diagnosis was confirmed by biopsy of the liver. The
      histopathology of the liver showed hyphae with the right-angle branching, typical
      of mucormycosis. The patient was managed with amphotericin B and operative
      correction of the perforated part of the small bowel was performed. However, the
      patient expired due to progressive hepatic failure despite corrective surgery and
      long-term amphotericin B therapy.

PMID- 10895982
TI  - Isolated splenic metastasis from colorectal carcinoma: a case report.
AB  - Isolated splenic metastasis arising from colorectal carcinoma is very rare and
      there has been only 6 cases reported in the English literature. A new case is
      presented, and its possible pathogenesis was considered with previously reported
      cases. A 65-year-old male patient had received a right hemicolectomy for
      ascending colon cancer 36 months earlier. He was followed up regularly with
      serial measurement of serum carcinoembryonic antigen (CEA). Rising serum CEA was
      discovered from 33 months postoperatively and CT revealed an isolated splenic
      metastasis. He therefore underwent splenectomy, which was proven to be a
      metastatic adenocarcinoma with similar histological feature to the original
      tumor. As all reported cases showed elevated serum CEA at the time of metastasis,
      isolated splenic metastasis might be associated with CEA in regard to its
      biological functions of immunosuppression and adhesion.

PMID- 10895983
TI  - Primary peritoneal pregnancy implanted on the uterosacral ligament: a case
      report.
AB  - Peritoneal pregnancies are classified as primary and secondary. Primary
      implantation on the peritoneum is extremely rare in extrauterine pregnancy and is
      a potentially life-threatening variation of ectopic pregnancy within the
      peritoneal cavity, representing a grave risk to maternal health. Secondary
      abdominal pregnancies are by far the most common and result from tubal abortion
      or rupture, or less often, after uterine rupture with subsequent implantation
      within abdomen. Early diagnosis and appropriate surgical management, regardless
      of stage of gestation, appear to be important in achieving good results. We
      report a case of primary peritoneal pregnancy in a 28-year-old woman, who had
      severe lower abdominal pain one day before laparotomy for a preoperative
      diagnosis of ectopic pregnancy. The conceptus was implanted on the left
      uterosacral ligament. A fresh embryo of approximately 8 weeks' gestation was
      found in the conceptus.

PMID- 10895984
TI  - Metastatic tumors in the sellar and parasellar regions: clinical review of four
      cases.
AB  - Metastatic tumors in the sellar and parasellar regions are uncommon and rarely
      detected in clinical practice. We present four cases of sellar and parasellar
      metastatic tumors, which metastasized from distant organ in one case and extended
      directly from adjacent structures in three. Common presenting symptoms were
      cranial neuropathies, headache and facial pain. Invasion into the cavernous sinus
      was noted in all cases. We report rare cases of sellar and parasellar metastases.
      Also, we should consider the possibility of metastasis in these regions for
      patients who showed the above clinical presentations in systemic cancer patients.
      In extensive diseases, transient symptomatic relief could be obtained by direct
      surgical management, even in restricted degree.

PMID- 10895985
TI  - Intradural extramedullary tuberculoma of the spinal cord: a case report.
AB  - Intradural extramedullary (IDEM) tuberculoma of the spinal cord is uncommon
      entity and moreover, few reports have been documented on concurrent IDEM and
      intracranial tuberculomas. Authors report a case of IDEM spinal tuberculoma
      having intracranial lesion simultaneously. A 49-year-old woman suffered from
      paraparesis and urinary incontinence while being given medical treatment for
      tuberculous meningitis. Magnetic resonance imaging (MRI) revealed an IDEM mass
      lesion between the T1 and T2 spinal levels, and multiple intracranial tuberculous
      granulomas. Surgical resection of the IDEM tuberculoma followed by anti
      tuberculous medication resulted in good outcome.

PMID- 10895986
TI  - Metabolism of desipramine in Japanese psychiatric patients: the impact of CYP2D6
      genotype on the hydroxylation of desipramine.
AB  - We investigated the impact of the genotype of CYP2D6 on the hydroxylation of
      desipramine in eighteen patients who were administered desipramine hydrochloride
      per os. Significantly higher plasma concentration of desipramine/daily dose of
      desipramine/body weight was observed in the subjects with two mutated alleles
      than in the subjects with either no mutated alleles or one mutated allele (two
      mutated alleles versus no mutated alleles=530.4+/-215.2 versus 118.1+/-63.9
      ng/ml/mg/kg, t=5.68, P<0.001; two mutated alleles versus one mutated
      allele=530.4+/-215.2 versus 176.2+/-62.3 ng/ml/mg/kg, P<0.001; One-way analysis
      of variance followed by Bonferroni's multiple comparison test, respectively).
      Significantly higher ratio of desipramine/2-hydroxy-desipramine was observed in
      the subjects with two mutated alleles compared to subjects with no mutated
      alleles or the subjects with one mutated allele (two mutated alleles versus one
      mutated allele= 4.39+/-0.36 versus 2.00+/-0.64, t=5.12, P<0.001; two mutated
      alleles versus no mutated alleles=4.39+/-0.36 versus 2.02+/-0.59, t=4.42,
      P<0.01). The genotyping of CYP2D6 only grossly predicts the steady state
      concentration of desipramine, mainly predicts the risk of getting very high
      plasma levels. Within each genotype there is marked interindividual variability.

PMID- 10895987
TI  - Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver
      microsomes.
AB  - Silibinin, the main constituent of silymarin, a flavonoid drug from silybum
      marianum used in liver disease, was tested for inhibition of human cytochrome P
      450 enzymes. Metabolic activities were determined in liver microsomes from two
      donors using selective substrates. With each substrate, incubations were carried
      out with and without silibinin (concentrations 3.7-300 microM) at 37 degrees in
      0.1 M KH2PO4 buffer containing up to 3% DMSO. Metabolite concentrations were
      determined by HPLC or direct spectroscopy. First, silibinin IC50 values were
      determined for each substrate at respective K(M) concentrations. Silibinin had
      little effect (IC50>200 microM) on the metabolism of erythromycin (CYP3A4),
      chlorzoxazone (CYP2E1), S(+)-mephenytoin (CYP2C19), caffeine (CYP1A2) or coumarin
      (CYP2A6). A moderate effect was observed for high affinity dextromethorphan
      metabolism (CYP2D6) in one of the microsomes samples tested only (IC50=173
      microM). Clear inhibition was found for denitronifedipine oxidation (CYP3A4;
      IC50=29 microM and 46 microM) and S(-)-warfarin 7-hydroxylation (CYP2C9; IC50=43
      microM and 45 microM). When additional substrate concentrations were tested to
      assess enzyme kinetics, silibinin was a potent competitive inhibitor of
      dextromethorphan metabolism at the low affinity site, which is not CYP2D6
      (Ki.c=2.3 microM and 2.4 microM). Inhibition was competitive for S(-)-warfarin 7
      hydroxylation (Ki,c=18 microM and 19 microM) and mainly non-competitive for
      denitronifedipine oxidation (Ki,n=9 microM and 12 microM). With therapeutic
      silibinin peak plasma concentrations of 0.6 microM and biliary concentrations up
      to 200 microM, metabolic interactions with xenobiotics metabolised by CYP3A4 or
      CYP2C9 cannot be excluded.

PMID- 10895988
TI  - DNA adduct levels and intestinal lesions in congenic rapid and slow acetylator
      syrian hamsters admi food mutagens 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP) or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ).
AB  - Epidemiological studies indicate that rapid acetylators with a high intake of
      well-done red meat have an increased risk of colorectal cancer. Arylamine N
      acetyltransferase enzymes (E.C. 2.3.1.5) activate carcinogenic heterocyclic
      amines found in the crust of fried meat via O-acetylation of their N
      hydroxylamines to reactive intermediates that bind covalently to DNA and produce
      mutations. Syrian hamsters as well as humans express two N-acetyltransferase
      isozymes (NAT1 and NAT2) which differ in substrate specificity and genetic
      control. Nucleic acid substitutions in the NAT2 gene segregate individuals into
      rapid, intermediate and slow acetylator phenotypes. In the present paper, we
      examined the role of the polymorphic NAT2 acetylator genotype in carcinogenesis
      induced by the food mutagens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) or 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) by comparing Syrian
      hamster lines congenic at the NAT2 locus. No differences were found between rapid
      and slow acetylator congenic hamsters in levels of intestinal PhIP-DNA adducts.
      In contrast to previous studies in rats, no carcinogen-related induction of the
      preneoplastic lesions aberrant crypt foci or tumors was found in the intestines
      of rapid and slow acetylator congenic Syrian hamsters administered PhIP or IQ.

PMID- 10895989
TI  - Prejunctional muscarinic receptor modulation of noradrenaline release from
      sympathetic neurones in rabbit aorta.
AB  - The prejunctional muscarinic modulation of stimulation-evoked release of 3H
      noradrenaline from sympathetic neurones in rabbit aorta was examined. The role of
      transmitter uptake, alpha-adrenoceptor blockade, stimulation frequency and
      endothelium on the modulation was investigated. Rings of aorta were incubated
      with (-)-3H-noradrenaline and subsequently subjected to electrical-field
      stimulation. Fractional 3H-overflow was determined by liquid scintillation
      counting. Acetylcholine (10(-8)-3 x 10(-6) M) added cumulatively, reduced the
      stimulation-evoked 3H-overflow up to 80%. The effect of acetylcholine was the
      same in intact and endothelium-free aorta. The inhibitory effect of acetylcholine
      was inversely related to the frequency of stimulation (1-10 Hz). The maximal
      inhibition (%) was 80 (1 Hz), 53 (3 Hz) and 14 (10 Hz). The inhibitory effect of
      acetylcholine (10(-6) M) and carbachol (10(-5) M) reached a maximum 15 min. after
      addition and then remained almost constant. Cocaine (3 x 10(-5) M) did not alter
      the effect of acetylcholine. Desipramine (10(-6) M) and corticosterone (4 x 10(
      5) M) attenuated the inhibition seen with low concentrations (10(-8)-10(-7) M) of
      acetylcholine. The acetylcholine-induced inhibition was antagonized by
      desipramine. Cocaine plus corticosterone attenuated the inhibition seen with high
      concentrations (10(-6)-3 x 10(-6) M) of acetylcholine. Rauwolscine (10(-6) M)
      enhanced the maximal inhibitory effect of acetylcholine. We conclude that the
      inhibitory effect of acetylcholine on 3H-overflow from rabbit aorta preloaded
      with 3H-noradrenaline is (1) inversely related to stimulation frequency; (2)
      independent of endothelium; (3) unaffected by neuronal and extraneuronal
      transmitter uptake; (4) that cocaine is not a prejunctional muscarinic
      antagonist; (5) that cocaine, but not desipramine, is suited as a neuronal uptake
      inhibitor in studies of prejunctional muscarinic receptor subtypes; and (6) and
      that there is an inverse interaction between prejunctional alpha2-adrenoceptors
      and muscarinic receptors.

PMID- 10895990
TI  - Regional differences in neurogenic signal transduction pathway of cholera toxin
      induced fluid, electrolyte and serotonin accumulation in the porcine jejunum.
AB  - Serotonin, acetylcholine and substance P are mediators involved in the secretory
      response to cholera toxin in the small intestine. The aim of this study was to
      investigate the regional difference in the effect of a serotonin receptor type 3
      antagonist (ondansetron), a nicotinic receptor antagonist (hexamethonium), and a
      substance P antagonist (the neurokinin receptor type 1 antagonist, CP 99,994) on
      the cholera toxin-induced fluid accumulation in the porcine jejunum. A dose-range
      of cholera toxin (0.32-56.00 microg/loop) was instilled for 4 hr in ligated loops
      in two regions of the proximal jejunum in 6-8-week-old pigs. Ondansetron (200
      microg/kg), hexamethonium (10 mg/kg), CP 99,994 (1 mg/kg), or saline alone
      (control) were given intravenously 10 min. before cholera toxin instillation.
      Cardiovascular parameters, blood gas data, net fluid accumulation, serotonin and
      electrolyte concentration in the accumulated fluid were measured. Cardiovascular
      and blood gas parameters were within the normal range in all treatments. The
      apparent maximal response in fluid accumulation was reduced 20% in case of
      ondansetron, and by 33% using CP 99,994 in the aboral region compared to control,
      whereas no effect was observed in the oral region. Hexamethonium reduced the
      apparent maximal secretory response in both the oral and aboral regions by 45%.
      None of the treatments with antagonists changed the luminal content of serotonin
      or the electrolyte concentrations in the accumulated fluid. The results
      demonstrate that the involvement of serotonin receptor type 3 and neurokinin type
      1 receptors in the transductional pathway of cholera toxin-induced fluid
      accumulation vary significantly within the jejunum, while the cholinergic
      (nicotinic) transmission plays an even role.

PMID- 10895991
TI  - Protective role of metallothionein on DNA damage in rat kidney caused by cis
      diamminedichloroplatinum.
AB  - Cis-diamminedichloroplatinum (cis-DDP) has been used as an anticancer agent but
      it also causes nephrotoxicity. To study the cis-DDP metabolism and its effects,
      the induction of metallothioneins and DNA damage caused by cis-DDP were observed.
      Cis-DDP or trans-DDP was administered to seven-week-old Wistar male rats as three
      daily injections of 8.0 mg/kg body wt., intraperitoneally. Using the obtained
      kidneys, gel filtration assay, metal analysis, immunohistochemistry and terminal
      deoxy transferase-mediated deoxy uracil triphosphate nick end labeling (TUNEL)
      method were carried out to examine localization of metallothioneins and DNA
      damage caused by cis-DDP. Platinum (Pt) contents, 26.05+/-12.01 microg/g body wt.
      and 51.29+/-4.59 microg/g body wt. (average+/-S.E.) were detected in the kidney
      of rats injected with both cis- and trans-DDP, respectively. Metallothionein was
      detected in the cortex of the kidney in rats administrated cis-DDP or trans-DDP.
      The mRNA was also detected in the same region. On the other hand cis-DDP showed
      induction of DNA damage on the cells in the outer stripe of the outer medulla but
      trans-DDP did not show any damage. The region-induced DNA damage differed from
      that induced by metallothioneins. Cis-DDP is suggested to be mainly trapped at
      the proximal tubules by metallothioneins, and the rest of cis-DDP induces DNA
      damage at the outer stripe of the outer medulla. Metallothioneins are considered
      to contribute to the protection against cis-DDP in the rat cortex.

PMID- 10895992
TI  - Amiodarone for rapid cardioversion of chronic atrial tachyarrhythmia?
AB  - Electrical cardioversion of atrial tachyarrhythmia has disadvantages, such as the
      need for general anaesthesia, skin burns and thoracic pain. Pharmacodynamic
      cardioversion is without these side effects, but the reports of the efficacy of
      the treatment vary a lot. Amiodarone has been the only drug so far reported to
      give a combination of high efficacy and low frequency of serious side effects
      such as ventricular tachycardia and shock. The purpose of the present study was
      to assess the effect of amiodarone on chronic atrial tachycardia. Seventeen
      patients with chronic atrial fibrillation or flutter were given an oral dose of
      30 mg/kg amiodarone. Serial blood tests after amiodarone ingestion were taken to
      document absorption. Patients, who did not convert to sinus rhythm within 24 hr
      were treated by electrical cardioversion. No patients converted
      pharmacodynamically to sinus rhythm. Twelve patients (71%) reached the
      recommended serum concentration of amiodarone (2-2.5 mg/l, median 2.4 mg/l, range
      0.96-4.7). The concentration of desethylamiodarone remained low (<0.2 mg/l), and
      there were no objective or subjective side effects following the treatment.
      Sixteen patients (94%) were converted to sinus rhythm the day after by electrical
      cardioversion without complications. A single high dose of amiodarone is a safe
      but ineffective method of converting chronic atrial fibrillation and flutter, and
      may be used as adjuvant therapy in combination with electrical cardioversion.

PMID- 10895993
TI  - Human isolated coronary artery contraction to sumatriptan characterised by the
      selective 5-HT1B/1D receptor antagonist GR55562.
AB  - The antimigraine drug, sumatriptan, contracts the human coronary artery both in
      vivo and in vitro. Because sumatriptan has been associated with cardiac side
      effects, it is important to characterise the receptor involved in sumatriptan
      induced coronary artery contraction. Using the agonists sumatriptan and 5
      carboxamidotryptamine and the selective 5-HT1B/1D receptor antagonist GR55562, we
      have investigated the involvement of 5-HT1B/1D receptors in the contraction of
      the human isolated coronary artery. Contractions to sumatriptan (pEC50: 6.1+/
      0.2, maximal effect: 21+/-4% of 100 mM K+-induced contraction) were competitively
      antagonised by GR55562. The pA2 of GR55562 (7.40+/-0.16) was in accord with its
      reported affinity at the human 5-HT1B receptor. Since the contractions to 5
      carboxamidotryptamine did not reach a maximum with the highest concentration used
      (10 microM), pEC50 values could not be calculated for Schild analysis. However,
      using the pEC10%/K+ values (negative logarithm of the concentration needed to
      induce 10% of the contraction to 100 mM K+), GR55562 proved a less potent
      antagonist against 5-carboxamidotryptamine than against sumatriptan. These
      results show that sumatriptan contracts the human isolated coronary artery via 5
      HT1B/1D receptors, most probably the 5-HT1B subtype. 5-Carboxamidotryptamine may
      contract the human isolated coronary artery, at least partly, via a novel yet to
      be characterised, receptor.

PMID- 10895994
TI  - Treadmill training with body weight support: its effect on Parkinson's disease.
AB  - OBJECTIVE: To test whether body weight-supported treadmill training (BWSTT) is
      effective in improving functional outcome of patients with Parkinson's disease.
      DESIGN: Prospective crossover trial. Patients were randomized to receive either a
      4-week program of BWSTT with up to 20% of their body weight supported followed by
      4 weeks of conventional physical therapy (PT), or the same treatments in the
      opposite order. Medications for parkinsonism were not modified throughout the
      study. SETTING: Inpatient rehabilitation unit for neurologic diseases. SUBJECTS:
      Ten patients (5 men, 5 women) with Hoehn and Yahr stage 2.5 or 3 parkinsonism;
      mean age 67.6 years, mean duration of Parkinson's disease 4.2 years. MAIN OUTCOME
      MEASURES: The Unified Parkinson's Disease Rating Scale (UPDRS), ambulation
      endurance and speed (sec/10 m), and number of steps for 10-meter walk. RESULTS:
      The mean total UPDRS before/after BWSTT was 31.6/25.6, and before/after PT was
      29.1/28.0. Analysis of covariance for improvement of UPDRS demonstrated a
      significant effect of type of therapy (F(1, 16) = 42.779, p < .0001) but not
      order of therapy (F(1, 16) = 0.157, p = .697 1). Patients also had significantly
      greater improvement with BWSTT than with PT in ambulation speed (BWSTT,
      before/after = 10.0/8.3; PT, 9.5/8.9), and number of steps (BWSTT, 22.3/19.6; PT,
      21.5/20.8). CONCLUSIONS: In persons with Parkinson's disease, treadmill training
      with body weight support produces greater improvement in activities of daily
      living, motor performance, and ambulation than does physical therapy.

PMID- 10895995
TI  - A taxonomy for classification of stroke rehabilitation services.
AB  - OBJECTIVE: To develop a taxonomy for use in measuring stroke rehabilitation
      services. DESIGN: A cross-sectional study using facility-level survey data and
      extant data files. SETTING: Veterans Administration medical centers (VAMCs).
      VARIABLES: (1) A list of rehabilitation characteristics, including personnel,
      physical facilities, coordination of care, and hospital characteristics; and (2)
      a classification or typology of VAMCs according to the type of postacute stroke
      care on-site. MAIN OUTCOME MEASURES: Data sources included extant Veterans
      Administration (VA) computerized databases, VA central office administrative
      files, and 2 mailed surveys to VA rehabilitation medicine services and stroke
      acute care services. The rehabilitation taxonomy was derived using 2 methods that
      assess face and construct validity, respectively: (1) an expert panel rating,
      using a modified Delphi process, of the clinical importance of each of the
      rehabilitation characteristics; and (2) a comparison of rehabilitation
      characteristics across the different types of VAMCs. Variables were included in
      the final taxonomy if the expert panel reached consensus that the variable was
      clinically important, or if there were statistically significant differences in
      these characteristics across the different types of medical centers. RESULTS: Of
      67 possible rehabilitation characteristics, a multidisciplinary expert panel
      reached consensus about the likely clinical importance of 21 rehabilitation
      characteristics, 11 of which showed statistically significant differences across
      different types of VAMCs. An additional 9 variables that lacked expert panel
      consensus differed significantly among the different medical centers. These 30
      variables represent a preliminary taxonomy of key rehabilitation characteristics.
      Among the 20 variables that varied significantly across the different types of
      medical centers, 18 showed a pattern with the greatest amount of resources and
      organizational sophistication being found in VAMCs with rehabilitation units,
      followed by medical centers with geriatric units, and the least amount of
      resources and organizational sophistication was seen in medical centers whose
      postacute care services were limited to nursing home or intermediate care.
      CONCLUSION: Thirty rehabilitation characteristics had face validity and/or
      construct validity, and can be considered to represent a preliminary taxonomy for
      measuring stroke rehabilitation services. This study also shows that there are
      significant differences among hospitals in resources and organization of care
      deemed to be important for stroke patients.

PMID- 10895996
TI  - The stroke impairment assessment set: its internal consistency and predictive
      validity.
AB  - OBJECTIVE: To study the scale quality and predictive validity of the Stroke
      Impairment Assessment Set (SIAS) developed for stroke outcome research. DESIGN:
      Rasch analysis of the SIAS; stepwise multiple regression analysis to predict
      discharge functional independence measure (FIM) raw scores from demographic data,
      the SIAS scores, and the admission FIM scores; cross-validation of the prediction
      rule. SETTING: Tertiary rehabilitation center in Japan. PATIENTS: One hundred
      ninety stroke inpatients for the study of the scale quality and the predictive
      validity; a second sample of 116 stroke inpatients for the cross-validation
      study. MAIN OUTCOME MEASURES: Mean square fit statistics to study the degree of
      fit to the unidimensional model; logits to express item difficulties; discharge
      FIM scores for the study of predictive validity. RESULTS: The degree of misfit
      was acceptable except for the shoulder range of motion (ROM), pain, visuospatial
      function, and speech items; and the SIAS items could be arranged on a common
      unidimensional scale. The difficulty patterns were identical at admission and at
      discharge except for the deep tendon reflexes, ROM, and pain items. They were
      also similar for the right- and left-sided brain lesion groups except for the
      speech and visuospatial items. For the prediction of the discharge FIM scores,
      the independent variables selected were age, the SIAS total scores, and the
      admission FIM scores; and the adjusted R2 was .64 (p < .0001). Stability of the
      predictive equation was confirmed in the cross-validation sample (R2 = .68, p <
      .001). CONCLUSIONS: The unidimensionality of the SIAS was confirmed, and the SIAS
      total scores proved useful for stroke outcome prediction.

PMID- 10895997
TI  - Correlation of polyelectromyographic patterns and clinical upper motor neuron
      syndrome in hemiplegic stroke patients.
AB  - OBJECTIVE: To investigate the correlation between movement patterns, measured by
      polyelectromyography (PEMG), and clinical upper motor neuron (UMN) syndrome in
      stroke patients. DESIGN: PEMG patterns, recorded from pairs of flexor-extensor
      muscles during voluntary maneuvers, and motor outcomes were assessed
      approximately 1 month after stroke (early stage). Motor outcomes were reassessed
      6 months later (late stage). PARTICIPANTS: Thirty-nine hemiplegic stroke patients
      and 18 healthy control subjects. MAIN OUTCOME MEASURES: Passive stretch reflexes
      (PSRs), Brunnstrom's stages, and walking ability. RESULTS: Six PEMG patterns,
      varying from complete reciprocal to complete synchrony, were identified. Higher
      PEMG pattern scores were associated with better Brunnstrom's stages (r > .80),
      walking ability (r > .39), and some PSRs (r < -.37). PEMG patterns could separate
      patterns 1 and 2 from patterns 3 and 4 for patients with early Brunnstrom's
      stages 1 and 2. Patterns 1 and 2 (reduced agonist electromyographic activities)
      indicated weakness and resulted in the worst motor outcomes. Patterns 3 and 4
      (cocontraction and coactivation) indicated spasticity and associated synergistic
      movements. Patients with patterns of 5 and 6 (reciprocal electromyographic
      activities) had more selective motor control. CONCLUSIONS: PEMG patterns
      correlate with clinical UMN syndromes and may allow treatment strategy planning
      on the basis of underlying motor control, as well as the prediction of final
      motor outcomes soon after stroke, even in patients who cannot move their legs
      initially.

PMID- 10895998
TI  - Factors predicting stroke disability at discharge: a study of 793 Chinese.
AB  - OBJECTIVE: To identify factors predicting stroke disability at discharge in a
      Chinese population. DESIGN: Retrospective analysis of data collected from stroke
      patients. SETTING: A 25-bed stroke rehabilitation unit in Hong Kong.
      PARTICIPANTS: A total of 793 Chinese patients with acute stroke consecutively
      admitted for inpatient rehabilitation. INTERVENTIONS: All patients received
      traditional rehabilitation therapies including physical, occupational, and speech
      therapies when appropriate. MAIN OUTCOME MEASURES: Disability was measured with
      the Barthel index (BI), and mild disability at discharge was defined as a BI
      score of > or =15. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      computed. RESULTS: Logistic regression analysis revealed that a BI score of > or
      = 15 points at admission strongly predicted that the patient's BI at discharge
      would be > or =15. For those whose BI score at admission was less than 15, these
      factors correlated negatively with a discharge BI of 15: BI at admission of <5
      (OR .08, CI .04-.17); National Institutes of Health stroke scale at admission of
      >7 (OR .23, CI .12-.43); urinary incontinence at admission (OR .35, CI .21-.60);
      age > or =65 years (OR .44, CI .25-.77); and abbreviated mental test at admission
      of <7 (OR .56, CI .33-.94). CONCLUSIONS: For Chinese stroke patients, the
      disability at admission is the most important predictor for disability at
      discharge. Patients with very severe disability, severe neurologic impairment,
      urinary incontinence, old age, and impaired cognition at admission are less
      likely to recover to mild disability at discharge. Although hemorrhagic stroke is
      more common among Chinese populations, it is not an independent predictor for
      disability at discharge.

PMID- 10895999
TI  - First-stroke recovery process: the role of family social support.
AB  - OBJECTIVE: To determine the role of family social support in three stroke
      rehabilitation variables (functional status, depression, social status) during a
      6-month recovery period. DESIGN: Assessment of first-stroke patients' functional
      status, depression, and social status before discharge and at 1, 3, and 6 months
      after stroke onset, in comparison with the amount of family social support
      received. The family social support scale--compliance, instrumental, and
      emotional support--was employed in the first month. SETTING: A university
      hospital and patients' residences. PATIENTS: A consecutive sample of 43 first
      stroke patients meeting the inclusion criteria. MAIN OUTCOME MEASURES: Changes of
      patients' rehabilitation variables over the 6-month period were tested by use of
      repeated multivariate analysis of variance measures. RESULTS: Observers of
      functional, depression, and social status changes were blind to patient grouping
      according to levels of family support. These three variables were significantly
      affected by higher levels of support (p = .001, p = .001, p = .020,
      respectively), but a significant interaction was found only with regard to
      functional status adjusted for initial stroke severity (p = .019). Patients with
      moderate/severe stroke and high levels of social support attained a significantly
      better and progressively improving functional status than those with less
      support. CONCLUSIONS: High levels of family support--instrumental and emotional-
      are associated with progressive improvement of functional status, mainly in
      severely impaired patients, while the psychosocial status is also affected.

PMID- 10896000
TI  - Electromechanical delay and reflex response in spastic cerebral palsy.
AB  - OBJECTIVE: Electromechanical delay (EMD) and reflex response in patients with
      spastic cerebral palsy (CP) were quantified and compared with those in normally
      developing individuals. It was hypothesized that the increased muscle stiffness
      associated with spasticity must make EMD shorter than the EMD of normally
      functioning muscles. DESIGN: Electromechanical reflex behavior was assessed in a
      case-control study. SETTING: Motion Analysis and Motor Performance Laboratory,
      University of Virginia, a tertiary clinical referral center and research
      facility. PARTICIPANTS: A volunteer sample of 12 children diagnosed with spastic
      CP and 12 age-matched, normally developing children recruited from the local
      community and clinical services. RESULTS: EMD in the patients with spasticity was
      significantly shorter than in the normally developing subjects, 40.5 msec and
      54.7 msec, respectively. The spastic group also had greater reflex activity, rate
      of force development, and antagonistic muscle activation. Knee flexion angle did
      not influence EMD in either group. CONCLUSIONS: Increased biomechanical stiffness
      in spastic muscle results in abnormally reduced EMD. Reciprocal excitation of
      antagonistic cocontraction was uniquely observed in the spastic group, but did
      not explain the reduced EMD.

PMID- 10896001
TI  - Muscle force production and functional performance in spastic cerebral palsy:
      relationship of cocontraction.
AB  - OBJECTIVE: To determine cocontraction's relation to strength and motor function
      in children with spastic cerebral palsy (CP). DESIGN: Prospective evaluation with
      a convenience sample of 10 subjects. SETTING: Pediatric rehabilitation center at
      a tertiary care hospital. PATIENTS: Ten ambulatory children with spastic CP, mean
      age 5 to 14yrs. MAIN OUTCOME MEASURES: A single comprehensive assessment of
      hamstring and quadriceps muscle strength; gait analysis while monitoring
      electromyographic (EMG) activity in those muscles; administration of the Gross
      Motor Function Measure (GMFM); heart-rate monitoring during quiet rest versus
      gait to compute an energy expenditure index (EEI). Cocontraction ratios and
      magnitudes were determined for the gait and strength testing trials using the EMG
      data. RESULTS: Cocontraction ratios during strength tests correlated directly
      with those during free gait. Cocontraction magnitude and total EMG magnitude had
      an inverse relationship to EEI; children with more muscle activity in the agonist
      and antagonist tended to be more energy efficient. Knee extensor muscle strength
      correlated positively with the GMFM and gait velocity. Neither cocontraction
      ratio nor magnitude during gait was related to strength. CONCLUSIONS: Children
      with CP used a similar muscle activation strategy across two different motor
      tasks. Strength and cocontraction were uniquely related to different aspects of
      motor function. Further research is needed to quantify more precisely
      cocontraction and force to EMG relations in this population.

PMID- 10896002
TI  - Hyperactive tendon reflexes in spastic multiple sclerosis: measures and
      mechanisms of action.
AB  - OBJECTIVE: To develop new measures of tendon reflexes and evaluate hyperactive
      reflexes in patients with spastic multiple sclerosis (MS). DESIGN: With the
      subject relaxed, a hand-held instrumented hammer was used to tap the patellar
      tendon and record the tapping force, while knee extension torque and quadriceps
      EMG were recorded isometrically as measures of the reflex response. SETTING:
      Research laboratory in a rehabilitation hospital. SUBJECTS: Ten spastic MS and 14
      healthy subjects. MAIN OUTCOME MEASURES: Tendon tapping force (designated as
      system input), reflex torque (as output), their dynamic relationship
      (characterized as system parameters tendon reflex gain, contraction rate, and
      reflex loop delay), Ashworth scale, and tendon reflex scale. RESULTS: The system
      parameters provide more repeatable measures than do input or output parameters
      alone because they quantify the input and output simultaneously and dynamically.
      Compared with control subjects, MS patients had a significantly lower threshold
      in tapping force (p = .026), yet their evoked reflex torque was significantly
      higher (p = .033). Despite significant quadriceps weakness (p < .0001), MS
      patients had a significantly higher reflex gain (p = .0002) and contraction rate
      (p = .0002), and shorter reflex loop delay (p = .0046), indicating
      hyperexcitability of motoneurons and peripheral receptors, and indicating that
      relatively more of the muscle was activated reflexively, with greater recruitment
      of larger fast-twitch fibers. Both the reflex gain and rate measures correlated
      more closely with the Ashworth scale and tendon reflex scale than did the output
      measures, indicating their potential clinical value. CONCLUSIONS: With
      appropriate simplification, the method may be used in clinical practice to
      quantify more precisely the tendon jerk than is currently feasible with standard
      clinical tests.

PMID- 10896003
TI  - Motor branch block of the rectus femoris: its effectiveness in stiff-legged gait
      in spastic paresis.
AB  - OBJECTIVE: To verify the efficacy of motor branch block of the rectus femoris for
      stiff-legged gait in spastic patients. DESIGN: Before-after treatment trial.
      SETTING: University hospital physical medicine and rehabilitation department
      outpatient clinic. PATIENTS: Thirty-one adult spastic patients with stiff-legged
      gait. INTERVENTION: Motor branch block of the rectus femoris with 2% lidocaine
      and 5% phenol. OUTCOME MEASURES: Subjective assessment of gait performance by
      patients themselves and objective assessment of gait speed and sagittal knee
      kinematics. RESULTS: Seventy-four percent (23/31) of patients felt an improvement
      (improved knee bending, disappeared toe dragging) after nerve block with
      lidocaine. Sixteen of 17 patients with an abnormal swing phase activity of the
      rectus femoris without that of the vastus medialis or lateralis and 20 of 23
      patients with a sufficient hip flexor strength expressed an improvement
      subjectively. Gait analysis showed increased maximal knee flexion at swing phase
      and increased slope of knee flexion curve at toe off (p < .05). Phenol block was
      performed in 19 of 23 patients who had had a subjective improvement in their gait
      performance after nerve block with lidocaine. Gait speed, maximal knee flexion
      angle at swing phase, and slope of knee flexion curve at toe off increased
      significantly after phenol block (p < .05). CONCLUSION: Motor branch block of the
      rectus femoris can be an effective treatment in stiff-legged gait. Its effect is
      varied with hip flexor strength and dynamic electromyographic findings of
      quadriceps.

PMID- 10896004
TI  - Fatigue of abdominal and paraspinal muscles during sustained loading of the trunk
      in the coronal plane.
AB  - OBJECTIVE: To measure fatigue-related changes in the electromyographic signals of
      trunk muscles during lateral bend loading, and to determine the effects of load
      magnitude, gender, and contraction time on these changes. DESIGN: A factorial
      experimental design. SETTING: A research laboratory. PARTICIPANTS: Twenty-four
      healthy volunteers (12 men, 12 women; mean age +/- SD, 22.9 +/- 3.1 yrs).
      INTERVENTION: Subjects sustained lateral bend loads at 20%, 40%, and 60% of their
      maximal exertion. OUTCOME MEASURES: Median frequency and total power of the power
      spectrum of the electromyographic signals. RESULTS: Trunk muscles' median
      frequency signals decreased and their total power increased as contraction time
      increased. These changes became more pronounced as the magnitude of loading
      increased. Men and women showed a similar rate of median frequency decline, but
      the total power of signals in men was larger than that in women. All muscles
      showed signs of fatigue, except that at 20% of maximal exertion only thoracic
      erector spinae fatigued significantly. CONCLUSIONS: Endurance training of
      paraspinal and abdominal muscles may be useful in preventing low back pain
      associated with lateral bend loading. The risk of back pain is similar in both
      genders and is higher with larger load magnitude and longer contraction time.

PMID- 10896005
TI  - Baclofen-induced cough suppression in cervical spinal cord injury.
AB  - OBJECTIVE: To determine the effect of the GABA-agonist baclofen on cough reflex
      sensitivity in subjects with cervical spinal cord injury (C-SCI). Baclofen has
      been shown to inhibit the cough reflex in able-bodied volunteers. DESIGN:
      Prospective, nonrandomized control trial. SETTING: Veterans Affairs medical
      center with large outpatient SCI population. PARTICIPANTS: Twelve adult males (11
      outpatients) with C-SCI chronically maintained on oral baclofen for the treatment
      of muscle spasm. INTERVENTION: Subjects underwent cough challenge testing with
      inhaled capsaicin. The concentrations (microM) of capsaicin inducing 2 or more
      (C2) and 5 or more (C5) coughs were determined. Mean values for log C2 and log C5
      were compared with a control group of outpatients with C-SCI not receiving
      baclofen. RESULTS: Subjects treated with baclofen had a significantly higher
      cough threshold (diminished cough reflex sensitivity) than control subjects. Mean
      (+/- standard error of the mean) values for log C2 in study subjects and controls
      were 1.28 +/- .16 and .65 +/- .15, respectively (p = .009). Mean values for log
      C5 in subjects receiving baclofen and in control subjects were 2.20 +/- .22 and
      1.43 +/- .23, respectively (p = .024). Subjects and controls did not differ in
      terms of age, spirometric parameters, or duration of injury. CONCLUSIONS: The
      results suggest that chronic therapy with baclofen diminishes cough reflex
      sensitivity in subjects with C-SCI. The clinical significance of this finding
      remains to be elucidated.

PMID- 10896006
TI  - Health outcomes among American Indians with spinal cord injury.
AB  - OBJECTIVE: To identify factors related to risk for poor health outcomes and
      secondary conditions in a sample of American Indians with spinal cord injury
      (SCI). DESIGN: Interviews were conducted by telephone with most participants;
      those who did not have telephones returned materials by mail. SETTING: A large
      rehabilitation hospital in the Western/ Mountain region of the United States.
      PARTICIPANTS: Ninety-seven American Indians with SCI completed a comprehensive
      health interview. All participants were adults with traumatic SCI and were at
      least 1 year postinjury. MAIN OUTCOME MEASURES: Selected items from the
      Behavioral Risk Factor Surveillance System were used to assess health behaviors
      and general health outcomes. Two secondary conditions were also investigated as
      outcome measures: pressure sores and post-SCI injuries. RESULTS: Multiple linear
      regression was used to predict seven health-related outcomes. Depressive
      symptomatology and post-SCI injuries were the primary predictors of the majority
      of health outcomes. Alcohol consumption was associated with a greater risk for
      post-SCI injuries, and being older at injury was associated with poorer health
      outcomes. CONCLUSIONS: Interventions to reduce depression, injuries, and alcohol
      misuse have potential for improving health among American Indians with SCI.

PMID- 10896007
TI  - Anxiety and depression after spinal cord injury: a longitudinal analysis.
AB  - OBJECTIVE: To examine the prevalence of anxiety and depression longitudinally in
      a sample of patients with a spinal cord injury (SCI). DESIGN: A prospective,
      longitudinal, multiple wave panel design with measures taken on 14 observational
      periods ranging from initial contact in the acute stages of hospitalization to 2
      years' postdischarge to the community. SETTING: The National Spinal Injuries
      Centre, Stoke Mandeville Hospital, Aylesbury, UK, and the general community.
      PARTICIPANTS: The cohort consisted of 104 patients with traumatic SCI (19 women,
      85 men), although the numbers assessed at each interval ranged from 5 to 85. MAIN
      OUTCOME MEASURES: Measures included the Beck Depression Inventory, the Beck
      Hopelessness scale, the State Anxiety Inventory, the functional independence
      measure, and the Social Support Questionnaire. RESULTS: When examined
      longitudinally, the data illustrate a consistent pattern of results across
      measures, with scores highest in the acute phase of the injury and during the
      months leading up to discharge. CONCLUSION: The numbers of persons scoring above
      clinical cut-off scores for anxiety and depression highlight the need to continue
      to ensure that appropriate psychological care is available within SCI
      rehabilitation settings. Moreover, the nature of the longitudinal results
      provides an indicator of subtle changes in anxiety and depression over time.

PMID- 10896008
TI  - Simulated work performance tasks in persons with neuropathic and myopathic
      weakness.
AB  - OBJECTIVES: To determine the test-retest reliability of selected simulated work
      performance tasks in persons with neuropathic and myopathic weakness and control
      subjects, and the association between muscular performance during these work
      tasks and conventional isolated muscle group testing. DESIGN: Measurement of
      three tasks performed on a work simulation device on two different days separated
      by 1 week. Associations between work task performance and previously reported
      strength measures in six muscle groups by hand-held dynamometry (HHD) were
      examined. SETTING: Human performance laboratory of a university. PARTICIPANTS:
      Convenience sample of ambulatory outpatients with hereditary motor and sensory
      neuropathy, type I (n = 9), myotonic muscular dystrophy (n = 10), and able-bodied
      controls (n = 11). MAIN OUTCOME MEASURES: For work simulation, isokinetic peak
      torque and total work; and for HHD, maximal isometric torque. RESULTS: Mean
      between-session differences for work simulation tasks ranged from -11% to +4% for
      peak torque and from -12% to +12% for total work; test sessions did not differ
      significantly for either patient or control groups. All groups had between
      session intraclass correlation coefficients usually >.80, indicating good
      consistency. In general, correlations between peak torque during work simulation
      and HHD were strongest in the control group. CONCLUSION: Persons with
      neuromuscular weakness reliably performed the simulated work tasks examined in
      this investigation. Work simulation tasks may be a useful tool to assess muscular
      performance in persons with neuromuscular weakness.

PMID- 10896009
TI  - Glenohumeral joint subluxation and reflex sympathetic dystrophy in hemiplegic
      patients.
AB  - OBJECTIVE: To examine the relation between glenohumeral joint subluxation and
      reflex sympathetic dystrophy (RSD) in hemiplegic patients. DESIGN: Case-control
      study. SETTING: Inpatient rehabilitation hospital. PATIENTS: Thirty-five
      hemiplegic patients with RSD (RSD group) and 35 hemiplegic patients without RSD
      (non-RSD group) were included in the study. Patients with rotator cuff rupture,
      brachial plexus injury, or spasticity greater than stage 2 on the Ashworth scale
      were excluded. MAIN OUTCOME MEASURES: Both the RSD and non-RSD groups were
      assessed for presence and grade of subluxation from radiographs using a 5-point
      categorization. The degree of shoulder pain of the non-RSD group was assessed by
      a visual analogue scale of 10 points. RESULTS: Glenohumeral subluxation was found
      in 74.3% of the RSD and 40% of the non-RSD group (p = .004). In the non-RSD
      group, 78.6% of the patients with subluxation and 38.1% of the patients without
      subluxation reported shoulder pain (p = .019). No correlation was found between
      the degree of shoulder pain and grade of subluxation in the non-RSD group (p =
      .152). CONCLUSION: Findings from this study suggest that shoulder subluxation may
      be a causative factor for RSD. Therefore, prevention and appropriate treatment of
      glenohumeral joint subluxation should be included in rehabilitation of hemiplegic
      patients.

PMID- 10896010
TI  - Incidence and risk factors associated with cardiac arrhythmias during
      rehabilitation after coronary artery bypass surgery.
AB  - OBJECTIVE: To evaluate the clinical relevance of cardiac arrhythmias during
      rehabilitation after coronary artery bypass graft (CABG) surgery. DESIGN: Survey
      of consecutive patients admitted to an inpatient cardiac rehabilitation center.
      SETTING: A rehabilitation center acting as a reference for cardiology clinics
      lacking this facility. The program was performed in the inpatient setting.
      PATIENTS: Two hundred sixty patients undergoing elective CABG surgery for angina.
      INTERVENTIONS: Four-week cardiac rehabilitation program. A 24-hour
      electrocardiographic examination was performed during the first 2 days and,
      subsequently, on a daily basis. MAIN OUTCOME MEASURES: Incidence and type of
      cardiac arrhythmias during rehabilitation; identification of factors associated
      with an increased risk of cardiac arrhythmias. RESULTS: Cardiac arrhythmias were
      recorded in 33.5% of the patients and were more frequent in patients with
      hypertension (47%), diabetes (42.4%), and hyperlipidemia (36.5%), compared with
      patients free from these diseases (15.5%) (p < .05). Arrhythmias were also
      recorded in patients older than 70 years (49%), compared with those younger
      (29.2%) (p < .01), and in patients who discontinued amiodarone (64.3%) compared
      with those who did not interrupt the drug (16%) (p < .005). Arrhythmias precluded
      rehabilitation in 5% of the patients and caused death in one patient. CONCLUSION:
      Surveillance for the development of cardiac arrhythmias during cardiac
      rehabilitation after CABG surgery may allow the early detection and treatment of
      arrhythmias in a substantial number of patients.

PMID- 10896011
TI  - Oxygen consumption during treadmill walking with and without body weight support
      in patients with hemiparesis after stroke and in healthy subjects.
AB  - OBJECTIVE: To compare oxygen consumption during walking with body weight support
      (BWS) with oxygen consumption during unsupported treadmill walking. DESIGN:
      Patient and reference group. Comparisons between two walking conditions within
      each group. SETTING: Research laboratory of a university hospital. PARTICIPANTS:
      Nonrandom convenience sample of 9 hemiparetic and 9 healthy subjects, mean age of
      56 and 57 years, respectively. INTERVENTIONS: The subjects walked on a treadmill
      with 0% and 30% BWS at their self-selected and maximum walking speeds. The trials
      were performed twice. MAIN OUTCOME MEASURES: Ventilatory oxygen uptake (VO2) and
      heart rate were measured by computerized breath-by-breath analysis and
      electrocardiography. RESULTS: VO2 was lower during walking with 30% BWS than
      during unsupported walking. At self-selected speed the Wilcoxon's signed rank p
      values were <.01 for both patients and reference group; at maximum velocity, p
      values were p < .02 for the patients and p < .05 for the reference group.
      Patients' heart rates were lower when they walked with 30% BWS than at 0% BWS, at
      both self-selected and maximum walking speeds (p < .05 and p < .02,
      respectively). CONCLUSIONS: The 30% body weight supported condition requires less
      oxygen consumption than full weight bearing. Treadmill training with BWS can be
      tolerated by patients with cardiovascular problems.

PMID- 10896012
TI  - Heart rate response to two lifting techniques.
AB  - OBJECTIVE: To determine the heart rate response to repetitive lifting of light
      weights employing two techniques, stoop and squat. DESIGN: Randomized cross-over
      trial. PARTICIPANTS: Twenty healthy volunteers (11 women, 9 men), mean age of 25
      years, recruited from the staff of a physical medicine and rehabilitation
      department. METHODS: Subjects lifted and lowered a box weighing 0, 1, or 3 kg,
      using the stoop (bent at waist with knees straight) and squat (knees bent)
      techniques, 20 times in 1 minute. MAIN OUTCOME MEASURES: The heart rate was
      recorded every 5 seconds during the effort aid 30 seconds and 1 minute after the
      test. RESULTS: Significantly higher heart rates were found during both the test
      and recuperation phases of the squat technique with each of the three loads (p <
      .05). The heart rate increase was also higher with the 3 kg load than with the 1
      kg or 0 kg load (p = .0001). CONCLUSION: The heart rate is lower using the stoop
      technique for lifting. This may explain why individuals choose the more
      ergonomically risky stoop technique in everyday lifting tasks.

PMID- 10896013
TI  - Low-intensity exercise as a modifier of physical frailty in older adults.
AB  - OBJECTIVE: To examine the effects of a 3-month low-intensity exercise program on
      physical frailty. DESIGN: Randomized clinical trial. SETTING: Regional tertiary
      care hospital and academic medical center with an outpatient rehabilitation
      fitness center. PARTICIPANTS: Eighty-four physically frail older adults (mean
      age, 83 +/- 4 yrs). INTERVENTION: Three-month low-intensity supervised exercise
      (n = 48) versus unsupervised home-based flexibility activities (n = 36). MAIN
      OUTCOME MEASURES: Physical performance test, measures of balance, strength,
      flexibility, coordination, speed of reaction, peripheral sensation. RESULTS:
      Significant improvement was made by the exercise group on our primary indicator
      of frailty, a physical performance test (PPT) (29 +/- 4 vs 31 +/- 4 out of a
      possible 36 points), as well as many of the risk factors previously identified as
      contributors to frailty; eg, reductions in flexibility, strength, gait speed, and
      poor balance. Although the home exercise control group showed increases in range
      of motion, the improvements in flexibility did not translate into improvements in
      physical performance capacity as assessed by the PPT. CONCLUSIONS: Our results
      suggest that physical frailty is modifiable with a program of modest activities
      that can be performed by virtually all older adults. They also indicate that
      exercise programs consisting primarily of flexibility activities are not likely
      to reverse or attenuate physical frailty. Although results suggest that frailty
      is modifiable, it is not likely to be eliminated with exercise, and efforts
      should be directed toward preventing the condition.

PMID- 10896014
TI  - Managing delayed-onset muscle soreness: lack of effect of selected oral systemic
      analgesics.
AB  - OBJECTIVE: To investigate the efficacy of commonly available analgesics in the
      management of delayed-onset muscle soreness over an 11-day period. DESIGN: Double
      blind, placebo-controlled randomized trial. SETTING: University laboratory.
      PARTICIPANTS: Sixty healthy volunteers (30 men, 30 women) with no current arm
      pain or pathology completed the experimental procedure. INTERVENTIONS: Subjects
      were randomly allocated to one of five experimental groups: control; placebo;
      aspirin (900 mg); codeine (60 mg); and paracetamol (1000 mg) (n = 12 in all
      groups). Delayed soreness was induced in the nondominant elbow flexors using a
      standardized exercise protocol of repeated eccentric contractions. MAIN OUTCOME
      MEASURES: Pain (visual analogue scale; McGill pain questionnaire [MPQ]), range of
      extension, flexion and resting angle (universal goniometer), and mechanical pain
      threshold (pressure algometer). Measurements were taken before and after drug
      administration each day, except for the MPQ, which was completed on the first and
      third days of the experiment. RESULTS: Analysis of results using repeated
      measures analysis of variance and relevant post hoc tests provided no evidence of
      the effectiveness of any of the preparations. CONCLUSION: There is no beneficial
      effect from the medications, at least at the doses stated, in the management of
      delayed-onset muscle soreness.

PMID- 10896015
TI  - Nonsurgical treatment of zygapophyseal joint cyst-induced radicular pain.
AB  - OBJECTIVE: To evaluate the role of fluoroscopically guided injection procedures
      in the nonsurgical treatment of zygapophyseal joint cyst-induced radicular pain.
      DESIGN: Retrospective study with independent clinical review. PARTICIPANTS:
      Fourteen patients (average age, 60.2 yrs), with an average symptom duration of
      18.8 months, were included. METHODS: Medical records were reviewed; patients with
      a radiographically observed zygapophyseal joint cyst that may have represented a
      compressive lesion corresponding to the patient's symptoms of radicular pain were
      eligible for inclusion. The level of nerve root involvement was confirmed by
      physical examination or electrodiagnostic findings. Patients whose root level
      involvement remained undetermined were required to demonstrate a positive
      response to a fluoroscopically guided diagnostic selective nerve root block
      (SNRB). Nonsurgical treatments included therapeutic SNRB, intraarticular
      zygapophyseal joint corticosteroid injection, and cyst puncture. Data collection
      and analysis were performed by an independent clinical reviewer. OUTCOME
      MEASURES: Pain score, work status, medication usage, and patient satisfaction
      with treatment. RESULTS: The majority of the observed cysts (71.4%) were at the
      L4-L5 level. Follow-up data collection was done at an average of 1.4 years after
      termination of treatment. An excellent outcome was observed in 4 patients
      (28.6%). Fifty percent of patients underwent surgery. CONCLUSIONS: Preliminary
      findings suggest a role for fluoroscopically guided injection techniques in the
      nonsurgical treatment of zygapophyseal joint cyst-induced radicular pain, with up
      to one-third of patients experiencing lasting symptomatic relief.

PMID- 10896016
TI  - Manual scapular stabilization: its effect on shoulder rotational range of motion.
AB  - OBJECTIVES: To study the effect of a recently described method of measuring
      shoulder rotational range of motion in which the scapula is manually stabilized,
      and to determine the reliability of that technique compared with measurements
      taken with the scapula unstabilized. DESIGN: Fifty high school athletes underwent
      measurement of shoulder rotational range of motion with and without the scapula
      manually stabilized. Measurements were performed by two groups of physical
      therapists blinded to the movement results, with repeat measurements performed 5
      days later. RESULTS: Rotational motion measured with the scapula stabilized was
      significantly less than when it was measured with the scapula unstabilized.
      Reliability was comparable for the two techniques when measuring external
      rotation, but the new technique was more reliable for measuring internal
      rotation. CONCLUSION: Scapular stabilization should be used when measuring
      internal rotation of the shoulder to obtain more accurate measurement of pure
      glenohumeral rotation. The technique described is promising, but warrants further
      refinement before it can be recommended for widespread clinical use. With
      practice, in experienced clinicians' hands, this technique may be the most
      reliable method for measuring outcome in clinical trials and for following
      clinically significant rotational motion deficits.

PMID- 10896017
TI  - Effect of varying frequency, intensity, and pulse duration of transcutaneous
      electrical nerve stimulation on primary hyperalgesia in inflamed rats.
AB  - OBJECTIVES: To examine the effect of varying frequency, intensity, and pulse
      duration of transcutaneous electrical nerve stimulation (TENS) on primary
      hyperalgesia (increased response to a noxious stimuli) to heat and mechanical
      stimuli induced by carrageenan paw inflammation in rats. DESIGN: Inflammation was
      induced by injection of 3% carrageenan into the hindpaw. Two frequencies (high,
      100 Hz; low, 4 Hz), 2 intensities (high, motor; low, sensory), and 2 pulse
      durations (100 microsec, 250 microsec) were applied for 20 minutes to the
      inflamed paw. The paw withdrawal latency (PWL) to radiant heat, threshold to
      mechanical stimuli, and spontaneous pain-related behaviors were measured before
      and 4 hours after induction of inflammation, after TENS, and at 8, 12, and 24
      hours after inflammation. A 3-factor (frequency, intensity, pulse duration)
      repeated-measures (time) design was used to analyze the changes in PWL.
      Mechanical threshold and spontaneous pain-related behaviors were compared for
      frequency, intensity, and pulse duration with a Kruskal-Wallis analysis of
      variance. RESULTS: For changes in PWL to heat, there was an effect for time (p =
      .0001) and frequency (p =.0001), but not for intensity (p = .45) or pulse
      duration (p = .21). For changes in mechanical threshold, there was also an effect
      for frequency (p = .007), but not for intensity (p = .055) or pulse duration (p =
      .058), after treatment with TENS. High-frequency TENS significantly reduced the
      primary hyperalgesia to heat and mechanical stimuli when compared with controls
      receiving no TENS or treatment with low-frequency TENS. High-frequency motor TENS
      also reduced spontaneous pain-related behaviors for 1 day after treatment.
      CONCLUSION: High-frequency TENS reduces primary hyperalgesia to heat and
      mechanical stimuli for up to 1 day after treatment. In contrast, low-frequency
      TENS is ineffective in reducing primary hyperalgesia. Varying intensity or pulse
      duration had no effect on the degree of antihyperalgesia produced by high
      frequency TENS.

PMID- 10896018
TI  - Superior mesenteric artery syndrome in traumatic paraplegia: a case report and
      literature review.
AB  - Superior mesenteric artery syndrome (SMAS) is a relatively rare condition thought
      to be caused by the functional obstruction of the third part of the duodenum as
      it passes between the superior mesenteric artery and the aorta. The following
      case report describes a patient who developed SMAS in the setting of traumatic
      paraplegia. The patient began to exhibit symptoms consistent with SMAS
      (epigastric pain, postprandial epigastric fullness, nausea, emesis) shortly after
      his injury and during home therapies. On admission to an inpatient rehabilitation
      hospital, the patient's symptoms persisted and prevented participation in any
      therapies. When radiographic studies demonstrated the existence of SMAS,
      conservative and surgical management were discussed with the patient and the
      family. The patient was managed conservatively with positional changes during
      feeding and the administration of metoclopramide (10mg orally, three times a day)
      before meals and before sleep. The patient was able to meet or exceed all short
      term physical and occupational therapy goals with one episode of postprandial
      nausea noted. The patient returned home 21 days after admission to the
      rehabilitation hospital with home therapies. The patient was able to perform
      transfer skills and most self-care tasks.

PMID- 10896019
TI  - Pure trigeminal motor neuropathy: a case report.
AB  - Pure trigeminal motor neuropathy is a trigeminal motor paralysis unaccompanied by
      signs of trigeminal sensory or other cranial nerve involvement. We present a case
      of a 38-year-old man complaining of progressive weakness and wasting of the right
      masticatory muscles after a bout of mild cold symptoms. No sensory symptoms were
      present. History, neurologic examination, electrophysiologic studies, and
      magnetic resonance imaging of the brain led to the diagnosis of pure trigeminal
      motor neuropathy. The cause may have been an autoimmune reaction to a viral
      infection.

PMID- 10896020
TI  - The reliability of centralized pain response.

PMID- 10896021
TI  - Passive leg cycling in persons with spinal cord injury.

PMID- 10896022
TI  - Carpal tunnel syndrome: the tethered median nerve test revisited.

PMID- 10896023
TI  - Role of nitric oxide in human pulmonary microvascular endothelial cell adhesion.
AB  - We examined the effect of nitric oxide (NO) on cell adhesion using cultured human
      pulmonary microvascular endothelial cells (PMVEC). Attachment of these cells to
      fibronectin was significantly inhibited by NO donors, spermine NONOate and S
      nitroso-N-acetyl-penicillamine or L-arginine, but not 8-bromoguanosine-3',5'
      cyclic-monophosphate. Similar results were obtained with the electrical cell
      substrate impedance sensor (ECIS) technique. Addition of NO donors or L-arginine,
      but not 8-bromoguanosine-3',5'-cyclic-monophosphate or N2,2'-O-dibutyrylguanosine
      3',5'-cyclic-monophosphate, to confluent PMVEC monolayers resulted in a transient
      decrease in cell adhesion, which was quantitated by the ECIS. Exposure to 1 U/ml
      alpha-thrombin reduced the monolayer electrical resistance by approximately 50%.
      The observed response was significantly suppressed by pretreatment of cells with
      intracellular calcium chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid or NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester,
      but not guanylate cyclase inhibitor, 6-anilino-5,8-quinoline-quinone. Selective
      knockout of endothelial NO synthase with antisense oligodeoxynucleotides also
      significantly reduced thrombin-induced decrease in monolayer resistance. Our
      findings indicate that thrombin stimulates calcium-dependent release of NO from
      PMVEC, which mediates the retraction of endothelial cells via a cGMP-independent
      pathway. Our results suggest that NO modulates cell-matrix and/or cell-cell
      adhesion in PMVEC and that this molecule might modify microvascular permeability
      in the human lung.

PMID- 10896024
TI  - Reduced inflammatory response in rats fed fat-rich diets: role of leukotrienes.
AB  - The effect of fat-rich diets on the acute inflammatory response was examined.
      Male Wistar rats aged 21 days were fed, for 6 weeks, with a control diet (4% fat
      content), or a control diet supplemented with coconut or soybean oils (15% fat
      content). Carrageenan-induced paw oedema and pleurisy were evaluated.
      Prostaglandin (PG) E2 and leukotriene (LT) C4/D4 concentrations were determined
      in the pleural exudate (ELISA). Pleural samples were tested for their effect on
      cutaneous vascular permeability of control rats and the effect of a LTD4 receptor
      antagonist (L660-711; 10 mg/kg; i.v.) examined. Relative to controls, rats fed
      both fat-rich diets presented a significant reduction in protein leakage and
      oedema formation without affecting the number of migrating leukocytes. Production
      of LTC4/D4 in pleural exudate was significantly increased from 1.8 +/- 0.2 ng/ml
      in controls to 2.8 +/- 0.2 and 3.0 +/- 0.3 ng/ml in animals fed coconut and
      soybean oil enriched diets, respectively, without changes in PGE2 production. The
      activity of these samples on cutaneous vascular permeability was 50% reduced,
      returning to control values after treatment of testing animals with a LTD4
      receptor antagonist. Rats fed fat-rich diets presented a reduced inflammatory
      response due, at least in part, to the LTC4/D4 mediated vasoconstrictor effect.

PMID- 10896025
TI  - Sildenafil relaxes rabbit clitoral corpus cavernosum.
AB  - The role of phosphodiesterase type 5 inhibition in the modulation of female
      sexual dysfunction was investigated by assessing its effects on in vitro
      relaxation of rabbit clitoris. Stimulation of the non-adrenergic, non-cholinergic
      neurons of the clitorus elicited a frequency-dependent relaxation response.
      Inhibition of NO synthase with L-NAME (100 microM) or inhibition of soluble
      guanylate cyclase with ODQ (1.0 microM) almost completely abolished the
      electrical field stimulation-induced relaxation of clitorus suggesting that NO
      cGMP pathway mediates the relaxation response to electrical field stimulation.
      Similarly, tetrodotoxin, a neuronal sodium channel blocker abolished the
      electrical field stimulation-induced clitoral relaxation implying a neuronal
      release of NO contributes to the electrical field stimulation elicited
      relaxation. Pretreatment of the clitoral corpus cavernosum strips with sildenafil
      (100 nM) enhanced the electrical field stimulation-induced relaxations both in
      magnitude and duration. The results suggest that sildenafil enhances electrical
      field stimulation elicited clitoral relaxation by a NO-cGMP dependent pathway.
      These data also imply that sildenafil may be useful to treat female sexual
      dysfunction.

PMID- 10896026
TI  - Modulation of acetylcholine release from mouse cortex by protein kinase C:
      dependence on stimulation intensity.
AB  - Activation of protein kinase C (PKC) results in enhanced action-potential evoked
      release of a variety of transmitters. However, previous studies have suggested
      that acetylcholine release is poorly modulated by PKC compared to other
      transmitter types. We investigated the effect of stimulation conditions on PKC
      modulation of electrical stimulation-induced acetylcholine release in mouse
      cortex, which were incubated with [3H]choline. The PKC activator phorbol
      dibutyrate (PDB) enhanced acetylcholine release at low stimulation frequencies
      (0.1 and 0.5 Hz) and not at 3 or 10 Hz. At 3 Hz stimulation, when release was
      inhibited by neostigmine, PDB enhanced acetylcholine release, suggesting that at
      low levels of acetylcholine release, exogenous activation of PKC can elevate
      acetylcholine release. However, at higher frequencies, PKC may already be
      endogenously activated since the PKC inhibitor polymyxin B (PXB) inhibited
      acetylcholine release. The other PKC inhibitors, Ro 318220, Go 6976,
      bisindolylmaleimide and calphostin C appeared to have no effect at 3 Hz. It may
      be that these inhibitors do not effectively block PKC in this functional system.
      Indeed, polymyxin B completely blocked the facilitatory effect of PDB but Ro
      318220 was without effect.

PMID- 10896027
TI  - Is a "color effect" demonstrated for hair analysis of carbamazepine?
AB  - Psillakis et al. have reported on the concentration of carbamazepine recovered
      from hair samples collected from patients receiving this anti-seizure medication
      under medical supervision and determined that their was a high correlation
      between dose and quantitation of recovered analyte. The analyte was identified by
      two techniques, FPIA (Abbott TDx) and HPLC and the correlation was high for both
      procedures. In the literature on hair analysis some have suggested that analyte
      concentration in hair is critically dependent on hair color. In reporting their
      data Psillakis et al. reported the hair color of each patient but made no attempt
      to analyze their results in relation to color. This article performs a secondary
      analysis of the Psillakis et al. data in order to determine whether there is a
      hair color effect discernible in the recovery of carbamazepine from hair.
      Analysis of this data set for both the FPIA and HPLC by one-way analysis of
      variance fails to identify a color effect at p = .05. Weighting the data for per
      patient dosage values fails to discern a color effect. Examination of all
      possible two-color comparisons also fails to identify a statistically significant
      effect for any subset of combinations. These data suggest that carbamazepine does
      not exhibit a color effect when using either FPIA or HPLC assay methods.

PMID- 10896028
TI  - Relationship between cocaine-induced hepatotoxic neurobehavioral & biochemical
      changes in mice: the antidotal effects of buprenorphine.
AB  - Cocaine (COCA)-induced neurobehavioral symptoms, which can be observed
      simultaneously with exacerbation in biochemical markers, were evaluated in mice,
      and compared with the changes observed in a representative hepatic failure model
      induced by thioacetamide (TAA). The effects of pretreatment with buprenorphine
      (BUP) (0.25, 0.5 or 1 mg/kg i.p.), a mixed opioid agonist-antagonist and an
      antidote against fatal COCA toxicity, were also examined. At 5 min after the COCA
      administration (65 mg/kg i.p.), the liver ATP levels were attenuated, and an
      exacerbation of the CNS-stimulating effects of COCA could be characteristically
      observed for hepatotoxicity-related neurobehavioral symptoms (changes in
      alertness, interest, body tension, head movement and walking). At 24 h, the ALT
      (alanine aminotransferase) activity was elevated, and hepatotoxic attenuation was
      observed for all of the scores on the neurobehavioral symptoms; this was almost
      identical to the symptoms observed in the TAA-treated group of mice. Recovery was
      observed by 72 h for all of the morbid changes. The hepatotoxic biochemical
      changes and the sum score for all five neurobehavioral symptoms were
      significantly ameliorated by low doses (0.25 and 0.5 mg/kg) of BUP, both at 5 min
      and 24 h.

PMID- 10896029
TI  - Human umbilical cord blood effect on sod mice (amyotrophic lateral sclerosis).
AB  - In previous studies we observed that human umbilical cord blood (HUCB) could have
      a protective effect on the onset of disease and time of death in MRL Lpr/Lpr mice
      which have an autoimmune disease that may be considered similar to human lupus.
      We believed a temporary xenograph may have occurred in these animals with the
      disease process delayed and the life span markedly increased. When HUCB is stored
      at 4 degrees C in gas permeable bags, there is a decrease of the cell reaction in
      mixed lymphocyte cultures. The blood, however, maintains a significant number of
      cells capable of producing replatable colonies. This study attempted to determine
      the effect of HUCB on SOD1 mice (transgenic B6SJL-TgN(SOD1-G93A)1GUR), which have
      a mutation of the human transgene, (CuZn superoxide dismutase gene SOD1) that has
      been associated with amyotrophic lateral sclerosis. We previously developed
      evidence that the survival of lethally irradiated mice was related to the number
      of human mononuclear cells administered. In the present study, we decided to
      investigate the effect of a relatively large dose of human mononuclear cord blood
      cells on SOD1 mice subjected to a sublethal dose of irradiation preceded by
      antikiller sera (rabbit anti-asialo). The SOD1 mice show evidence of paralysis at
      4 to 5 months. The average expected lifetime of these mice is reported to be 130
      days (Jackson Laboratory). In this experiment, there were 23 mice. Two mice died
      before the onset of paralysis. The remainder were divided into three groups:
      group I: control group of 4 untreated mice; group II: an experimental group of 6
      mice treated with antikiller sera, 800 cGy irradiation plus 5 x 10(6) congenic
      bone marrow mononuclear cells; group III: another experimental group of 11 mice
      treated with antikiller sera, 800 cGy irradiation plus 34.2-35.6 x 10(6) HUCB
      mononuclear cells, previously stored for 17-20 days at 4 degrees C in gas
      permeable bags. The results were as follows: the average age at death was: (I)
      127 days for the untreated control group, (II) 138 days for the group that
      received 800 cGy of irradiation and congenic bone marrow (BM) and (III) 148 days
      for the group that received irradiation and HUCB. (P < 0.001 HUCB vs control, p <
      0.01 HUCB vs BM). The longest surviving mouse in each group was 131, 153, and 182
      days old respectively. In summary, large doses of HUCB mononuclear cells produced
      considerable delay in the onset of symptoms and death of SOD1 mice. These
      preliminary results may not only indicate that amyotrophic lateral sclerosis is
      an autoimmune disease, but may also indicate a possible treatment for a
      devastating disease and possibly others.

PMID- 10896030
TI  - Receptor selectivity of Met-enkephalin-Arg6-Phe7, an endogenous opioid peptide,
      in cerebral cortex of human and rat.
AB  - This study was undertaken to examine the receptor selectivity of Met-enkephalin
      Arg6-Phe7 (MERF) employing radioreceptor binding assays in human cerebral cortex
      membranes, and to elucidate the responsible receptors that mediate the regulatory
      action of MERF on high (20 mM) K+-stimulated release of [3H]norepinephrine ([3H]
      NE) in rat cortex slices. Specific binding of [3H]MERF was inhibited by DAMGO,
      Tyr-D-Arg-Phe-Sar(TAPS), bremazocine and ethylketocyclazocine (EKC), but not by
      U69,593 (U69) and DPDPE. MERF showed high affinity for specific binding sites of
      [3H]DAMGO. However, MERF had little influence on the specific binding of
      [3H]DPDPE, [3H]U69 and [3H]diprenorphine ([3H]DIP) in the presence of 1 microM
      each of DAMGO, DPDPE and U69. In [3H]NE release experiments using rat cortex
      slices, DAMGO, MERF and EKC, in order of their potency, inhibited K+-stimulated
      release of [3H]NE. The inhibitory effects of MERF and DAMGO were more sensitive
      than that of EKC to antagonism by CTAP, nor-binaltorphimine (nor-BNI) and
      naloxone. These results suggested that MERF possesses high affinity for mu
      receptors, but not for delta-, kappa1-, and very low affinity for kappa2
      receptors in human cerebral cortex membranes. Also, the inhibitory effect of MERF
      on the K+-stimulated release of [3H]NE appears to be mediated by mu-receptors in
      rat cerebral cortex slices.

PMID- 10896031
TI  - Effects of bimoclomol, the novel heat shock protein coinducer, in dog ventricular
      myocardium.
AB  - The effects of the novel HSP-coinducer bimoclomol was studied on action
      potentials, ionic currents and [Ca2+]i transients in isolated canine ventricular
      myocytes using conventional microelectrode techniques and whole cell voltage
      clamp combined with fluorescent [Ca2+]i measurements. Contractility was studied
      in right ventricular trabeculae. All preparations were paced with a frequency of
      0.2 Hz. Bimoclomol (100 microM) shortened action potential duration measured at
      50% repolarization, but lengthened action potentials at the 90% repolarization
      level, decreased action potential amplitude and maximum depolarization velocity
      in a reversible manner. In voltage clamped myocytes, the drug activated a steady
      state outward current at positive membrane potentials leaving the peak inward
      current unaffected. [Ca2+]i transients, measured under voltage clamp control,
      were increased in amplitude and had accelerated decay kinetics in the presence of
      the compound, in addition to reduction of diastolic [Ca2+]i. Bimoclomol
      significantly decreased the force of contraction in right ventricular trabeculae.
      Comparison of present data to previous results indicate that the cardiac effects
      of bimoclomol strongly depend on actual experimental conditions. The reduced
      contractility in spite of the increased amplitude of [Ca2+]i transients suggests
      that 100 microM bimoclomol may decrease calcium sensitivity of the contractile
      apparatus.

PMID- 10896032
TI  - Comparison of the effects of zolpidem and zopiclone on nocturnal sleep and sleep
      latency in the morning: a cross-over study in healthy young volunteers.
AB  - Zolpidem (ZOL) and zopiclone (ZPC) are non-benzodiazepine hypnotics, with unique
      effects on sleep architecture compared with conventional benzodiazepines. The two
      compounds have different profiles in action to two major subtypes of the GABA-A
      receptors, therefore different effects on sleep structure may be expected. In the
      present study, the effects of ZOL (10mg) and ZPC (7.5mg) were compared in nine
      healthy young male subjects during nine-night sessions, employing a crossover
      design. Time courses during the sessions were significantly different between the
      compounds in the ratio (%) of S2 and S1. Compared to the baseline, an increase of
      S2 and a decrease of S1 and SR were caused by ZPC, not by ZOL. SWS was increased
      by both ZPC and ZOL. Significant changes by ZOL were found during the first 150
      min, while changes by ZPC were mostly observed during the second 150-min. This
      might be related to their half-lives. ZOL did not affect sleep latency in the
      morning, while ZPC caused a significant decrease. Subjective sleepiness, however,
      was not increased in the ZPC or ZOL mornings. It was speculated that difference
      in the action to the GABA-A receptor subtypes might be related to the differences
      in the effects on the sleep architecture between the compounds.

PMID- 10896033
TI  - Morin hydrate: a potential antioxidant in minimizing the free-radicals-mediated
      damage to cardiovascular cells by anti-tumor drugs.
AB  - The co-incubation of morin hydrate with either doxorubicin or mitomycin C could
      minimize the toxicity of these anti-tumor drugs on cardiovascular cells, such as
      red blood cells, human umbilical vein endothelial cells (ECV304) and primary
      mouse cardiomyocytes, whereas morin hydrate did not lower the cytotoxicity of the
      drugs on human hepatocellular carcinoma cells (HepG2). Morin hydrate may not
      exert its antioxidant effect by enhancing the antioxidant enzymatic activity
      because it did not cause any induction on the mRNA levels of manganese superoxide
      dismutase expression in ECV304 cells and HepG2 cells.

PMID- 10896034
TI  - Micro-spoon technique in estimation of sperm concentration in rat epididymis.
AB  - Several technical procedures were described for estimation of epididymal sperm
      concentration until today. In all of the described techniques, epididymal
      material was drawn into a micro-pipette before counting procedure. We aimed to
      proceed this stage without using any pipette because of the difficulty in
      aspirating very viscous epididymal material into a micro-pipette. For measuring
      epididymal material we used a 2 microl reservoir which we named as a micro-spoon.
      It was filled with the epididymal material and layered in a tube with Ringer's
      solution of 2 ml containing sodium hyaluronate. Then, it was mixed in order to
      obtain 1/1000 diluted suspension. Sperm cells in this suspension were counted on
      a Makler chamber under a light microscope. The procedure was easy and time
      saving, compared to the other techniques.

PMID- 10896035
TI  - Auto iris pigment epithelial cell transplantation in patients with age-related
      macular degeneration: short-term results.
AB  - Autologous iris pigment epithelial cell transplantation was performed on patients
      with exudative age-related macular degeneration (AMD). Autologous IPE cell
      culture was performed using autologous serum after iridectomy in 7 patients with
      AMD. The cell suspensions (2 approximately 20 x 10(4) cells) were transplanted
      into the submacular lesion of individuals after removal of neovascular membranes.
      Subsequent ophthalmological examinations, including best corrected visual acuity
      and fluorescein or indocyanine green angiography, were performed. In addition, 15
      patients with AMD, who underwent removal of neovascular membrane without
      transplantation, were evaluated as non randomized controls. Varying degrees of
      atrophy or defects of choriocapillaris and retinal pigment epithelium were
      observed in all of the patients. No cystoid macular edema or fluorescein leakage
      was observed after treatment, but window defects were present. No patient had
      decreased visual acuity. One treated patient developed mild subretinal fibrosis
      and an other patient developed mild preretinal fibrosis, however no difference
      was significant when compared with the control. In conclusion, the treatment
      resulted in no significant improvement in macular function, as compared with the
      control; however, no rejection or deterioration in visual acuity occurred up to
      the 13 month follow up.

PMID- 10896036
TI  - Tissue doppler imaging of left and right ventricles in normal children.
AB  - Tissue Doppler imaging is a new ultrasound technology that derives measurements
      of contraction and relaxation velocities directly from the myocardium. However,
      data on myocardial velocities by using tissue Doppler imaging have not been
      established in normal children. In 48 normal children, myocardial velocities were
      measured using tissue Doppler imaging at three different sites (base, middle, and
      apex) in the left and right ventricles and the interventricular septum. In the
      left ventricular wall, the peak myocardial velocities during early diastole (peak
      E), during atrial contraction (peak A), and during systole (peak S) waves
      decreased gradually between the base and apical sites, whereas the ratio of E to
      A waves (peak E/A wave ratio) did not change among the 3 segments. Similar
      findings were obtained from the myocardial velocities in the right ventricle and
      the interventricular septum. A systolic and diastolic velocity gradient was also
      observed between the different ventricular walls. Significant correlations of the
      tissue Doppler parameters with age or heart rate were observed. In the left
      ventricle, the peak E wave demonstrated a stronger relation with age (r=0.77)
      than with heart rate (r=-0.65). The peak A wave did not change with age but
      correlated with heart rate. The peak E/A wave ratio showed a weaker relation with
      age (r=0.54) than with heart rate (r=0.62). The peak S wave was related to age
      (r=0.65) and to a lesser extent to heart rate (r= -0.51). Similar relationships
      of tissue Doppler parameters with age or heart rate were observed for the right
      ventricle and interventricular septum. The heterogeneous pattern and age- and
      heart-rate-related changes in normal myocardium demonstrated in this study must
      be taken into account when attempting to identify altered regional myocardial
      function with tissue Doppler echocardiography.

PMID- 10896037
TI  - Unique electroencephalographic change of acute encephalopathy in glutaric
      aciduria type 1.
AB  - We report the peculiar serial electroencephalographic (EEG) findings in a 7-year
      old boy with glutaric aciduria type 1 during an episode of acute encephalopathy.
      The patient developed Reye-like syndrome triggered by cellulitis. Cranial
      magnetic resonance imaging demonstrated diffuse softening of cerebral hemisphere.
      The EEG on the day following onset of acute encephalopathy showed suppression
      burst pattern including continuous 14-15 Hz rhythmic waves at first. Then,
      periodic synchronous discharge appeared and lasted for about 40 minutes. Periodic
      synchronous discharge finally disappeared and nearly total electrocerebral
      silence continued. There have been no reports indicating such a change of EEG in
      a short period. The serial EEG changes probably reflect the process of electrical
      death of neurons in cerebral hemispheres.

PMID- 10896038
TI  - Broad specificity in binding of NIPP-1, nuclear inhibitor of protein phosphatase
      1, to PP1 isoforms in vivo.
AB  - Protein phosphatase type-1 (PP1), one of the most abundant Ser/Thr protein
      phosphatases, plays a central role in the regulation of various cell functions.
      Almost all the PP1 molecules exist as holoenzymes in vivo consisting of a
      catalytic subunit (PP1C) and a variable regulatory subunit that regulates
      substrate specificity and/or subcellular localization. In order to clarify fine
      regulation of PP1, we overexpressed a nuclear inhibitor of PP1 (NIPP-1) in a Flag
      tagged form in mammalian cells. The Flag-tagged NIPP-1 was found to be
      immunoprecipitated with three isoforms of PP1C, namely, PP1alpha, PP1gamma1, and
      PP1delta with a similar efficiency, suggesting that NIPP-1 makes a complex with
      the PP1C through the region conserved among the three isoforms. These results
      suggested that NIPP-1 can be involved in the regulation of various PP1
      holoenzymes in vivo.

PMID- 10896039
TI  - The effect of globopentaosylceramide on a depression model, mouse forced
      swimming.
AB  - We investigated the late effects of serotonergic drugs on mouse forced swimming
      and found that serotonin 1A antagonist NAN-190 hydrobromide (NAN-190) and
      serotonin 2 agonist R(-)-DO1 hydrochloride (DO1) increase the typical anti
      depressive behavior climbing 6 hours after the intraperitoneal injection. With
      the use of ion exchanger, ultra filtration and chemical extraction methods, a
      substance having remarkable anti-depressive activity on mouse forced swimming was
      extracted from the serums of the mice treated with the drugs. The substance was
      strongly suggested to be a glycolipid having a specific sugar chain structure
      GalNAcalpha1-3GalNAc in its terminal. In fact, globopentaosylceramide, another
      glycolipid having the structure in the terminal also showed marked anti
      depressive activity on mouse forced swimming, but globotetraosylceramide lacking
      the sugar chain structure did not. The GalNAcalpha1-3GalNAc-lipid reactivity in
      the serum and typical anti-depressive behavior climbing increased corresponding
      to the doses of NAN-190 and DO1. These findings clearly indicate that the
      terminal structure GalNAcalpha1-3GalNAc has the essential role in the anti
      depressive activity of globopentaosylceramide, and that serotonin 1A antagonism
      and serotonin 2 agonism increase the production of an anti-depressive glycolipid
      having the terminal structure in mouse serum.

PMID- 10896040
TI  - A new method to identify the internal auditory canal during the middle cranial
      fossa approach: a preliminary report.
AB  - A new method which facilitates identification of the internal auditory canal
      during the middle cranial fossa approach is described. This method uses
      illumination of the external auditory meatus as a guide to the internal auditory
      canal. When the external auditory meatus is illuminated by a light source system
      such that used for a flexible fiberscope, areas of the middle ear air cell system
      are illuminated and observable through the plate of bone constituting the base of
      the middle cranial fossa. In the case of ordinary pneumatization of the middle
      ear system, the attic is the site of the most intense illumination. Knowledge of
      the exact location of the attic obtained by this new method is extremely useful
      when performing drilling to expose the internal auditory canal in the middle
      cranial fossa approach. This is because the internal auditory canal is located
      medial to the attic, and also because such knowledge is helpful in identifying
      the two conventional landmarks of this approach, i.e., the arcuate eminence and
      the greater superficial petrosal nerve, as the locations of these structures are
      intimately related to the attic. The method described is very simple, timesaving
      and inexpensive, and is very helpful in detecting the internal auditory canal.
      Further anatomical study is being undertaken to establish a method of pinpointing
      the internal auditory canal, starting from the attic which is readily
      identifiable by use of this method.

PMID- 10896041
TI  - Cytocompatibility of UV and visible light photoinitiating systems on cultured
      NIH/3T3 fibroblasts in vitro.
AB  - This work investigates the cytocompatibility of several photoinitiating systems
      for potential cell encapsulation applications. Both UV and visible light
      initiating schemes were examined. The UV photoinitiators included 2,2-dimethoxy-2
      phenylacetophenone (Irgacure 651), 1-hydroxycyclohexyl phenyl ketone (Irgacure
      184), 2-methyl-1-[4-(methylthio) phenyl]-2-(4-morpholinyl)-1-propanone (Irgacure
      907), and 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (Darocur
      2959). The visible light initiating systems included camphorquinone (CQ) with
      ethyl 4-N,N-dimethylaminobenzoate (4EDMAB) and triethanolamine (TEA) and the
      photosensitizer isopropyl thioxanthone. A cultured fibroblast cell line, NIH/3T3,
      was exposed to the photoinitiators at varying concentrations from 0.01% (w/w) to
      0.1% (w/w) with and without the presence of initiating light. The results
      demonstrated that at low photoinitiator concentrations (< or = 0.01% (w/w)), all
      of the initiator molecules were cytocompatible with the exception of CQ, Irgacure
      651, and 4EDMAB which had a relative survival approximately 50% lower than a
      control. In the presence of low intensity initiating light (approximately 6 mWcm(
      2) of 365 nm UV light and approximately 60 mWcm(-2) of 470-490 nm visible light)
      and initiating radicals, Darocur 2959 at concentrations < or = 0.05% (w/w) and CQ
      at concentrations < or = 0.01% (w/w) were the most promising cytocompatible UV
      and visible light initiating systems, respectively. To demonstrate the potential
      use of cytocompatible photoinitiating systems in cell encapsulation applications,
      chondrocytes were encapsulated in a photocrosslinked hydrogel using 0.05% (w/w)
      Darocur 2959 (cytocompatible) and 0.01% (w/w) Irgacure 651 (cyto-incompatible).
      After photopolymerizing for 10 minutes with approximately 8 mWcm(-2) of 365 nm
      light, nearly all the chondrocytes survived the process with Darocur 2959 while
      very few of the chondrocytes survived the process with Irgacure 651.

PMID- 10896042
TI  - Phase transfer and characterization of poly(epsilon-caprolactone) and poly(L
      lactide) microspheres.
AB  - A method suitable for transfer of poly(epsilon-caprolactone) and poly(L-lactide)
      microspheres (synthesized by pseudoanionic dispersion polymerization of epsilon
      caprolactone and L-lactide in heptane-1,4-dioxane mixed solvent) from heptane to
      water was developed. This method consists of treating the microspheres with KOH
      ethanol in the presence of surfactants (nonionic Triton X-405, anionic sodium
      dodecyl sulfate (SDS), and zwitterionic ammonium sulfobetaine-2 (ASB)). Partial
      hydrolysis of polyesters results in the formation of hydroxyl and carboxyl groups
      in the surface layer of microspheres and enhances their stability in water-based
      media. Minimal concentrations of surfactants, needed to obtain stable suspensions
      of particles, were equal to 3 x 10(-2) and 6 x 10(-2), and 3 x 10(-2) mol l(-1)
      for Triton X-405. SDS, and ASB, respectively. In the case of poly(epsilon
      caprolactone) microspheres, suspensions in water were stable for all three
      surfactants for pH values ranging from 3 to 11. Suspensions of poly(L-lactide)
      were stable in the same range of pH values only for ASB. Surface charge density
      determined by electrophoretic mobility varied for poly(epsilon-caprolactone)
      microspheres from 2.6 x 10(-7) to 8.9 x 10(-7) mol m(-2), for particles
      stabilized with Triton X-405 and ASB. respectively. In the case of poly(L
      lactide) microspheres, surface charge density varied from 3.9 x 10(-7)
      (stabilizer: Triton X-405) to 7.4 x 10(-7) mol m(-2) (stabilizer: ASB). Carboxyl
      groups located in the surface layer of poly(L-lactide) microspheres were used for
      covalent immobilization of 6-aminoquinoline, a fluorophore with an amino group.
      Maximum surface concentration of immobilized 6-aminoquinoline was equal to 1.9 x
      10(-6) mol m(-2). Poly(epsilon-caprolactone) microspheres transferred into water
      were loaded with ethyl salicylate. Loading up to 38% (w/w) was obtained.

PMID- 10896043
TI  - In vitro testing of ten bone cements after different time intervals from
      polymerization.
AB  - Biological response of cells to implanted bone cement is a fundamental but often
      neglected issue in successful cemented implants. In this study, ten acrylic bone
      cements for orthopedics were assayed using two different in vitro testing methods
      on L929 cells. The cements were mixed as prescribed, cured for either 1 h or 7
      days and then extracted in minimum essential medium (MEM) according to the ISO
      standard for the preparation of samples. For the evaluation of cytotoxicity, the
      neutral red uptake assay (NRU) and the incorporation of propidium iodide (PI)
      were used to detect the viability/death of cells. The two methods were shown to
      be well correlated (p < 0.0001) in the case of both the 1-h and the 7-day
      extracts. Two cements, i.e. CERIM LT and CMW2, were found to be toxic after 1-h
      curing through both the spectrophotometric NRU assay and the cytofluorometric
      assay with PI. After 7-day curing, these two cements, as well as the Zimmer-low
      viscosity cement, were toxic according to the NRU assay. The toxic effect of all
      the cements disappeared after dilution of extracts 1:2 with MEM, except in the
      case of CERIM LT. In the search for the component inducing the toxic effect, the
      possible contribution of the residual monomer was discarded on the basis of
      literature data and the influence of various other factors was analyzed,
      including the contrast medium (barium sulphate or zirconium dioxide) and the
      concentrations of N,N-dimethyl-paratoluidine and of benzoyl peroxide (< 1% or >
      or = 1%). Unlike zirconium dioxide, barium sulphate was found to damage the cells
      at the 1-h endpoint. Benzoyl peroxide at concentration > or = 1% was found to
      affect cells at the same endpoint, whereas dimethylparatoluidine had no effect
      regardless of the proportion.

PMID- 10896044
TI  - Physiological and cell biological aspects of perfusion culture technique employed
      to generate differentiated tissues for long term biomaterial testing and tissue
      engineering.
AB  - Optimal results in biomaterial testing and tissue engineering under in vitro
      conditions can only be expected when the tissue generated resembles the original
      tissue as closely as possible. However, most of the presently used stagnant cell
      culture models do not produce the necessary degree of cellular differentiation,
      since important morphological, physiological, and biochemical characteristics
      disappear, while atypical features arise. To reach a high degree of cellular
      differentiation and to optimize the cellular environment, an advanced culture
      technology allowing the regulation of differentiation on different cellular
      levels was developed. By the use of tissue carriers, a variety of biomaterials or
      individually selected scaffolds could be tested for optimal tissue development.
      The tissue carriers are to be placed in perfusion culture containers, which are
      constantly supplied with fresh medium to avoid an accumulation of harmful
      metabolic products. The perfusion of medium creates a constant microenvironment
      with serum-containing or serum-free media. By this technique, tissues could be
      used for biomaterial or scaffold testing either in a proliferative or in a
      postmitotic phase, as is observed during natural development. The present paper
      summarizes technical developments, physiological parameters, cell biological
      reactions, and theoretical considerations for an optimal tissue development in
      the field of perfusion culture.

PMID- 10896045
TI  - Surface photo-grafting of polyurethane with 2-hydroxyethyl acrylate for promotion
      of human endothelial cell adhesion and growth.
AB  - Cytocompatible polyurethane (PU) surface was prepared by photo-grafting 2
      hydroxyethyl acrylate (HEA) onto the membrane surface. Graft polymerization was
      conducted by combining the use of the photo-oxidation and irradiation grafting.
      PU membrane was photo-oxidized to introduce the hydroperoxide groups onto the
      surface, then the membrane, immersed previously in monomer solution, was
      irradiated under UV light. The ATR-FTIR spectra, element spectroscopy for
      chemical analysis (ESCA), scanning electron microscopy (SEM) and water contact
      angle characterized the grafted copolymers and verified the occurrence of graft
      polymerization. The results showed that UV irradiation could realize the graft
      polymerization effectively and the grafting was confined within the surface
      layer. The grafted membrane showed minimal surface morphology. Human umbilical
      vein endothelial (HUVE) cells were seeded on the grafted surface. The performance
      of the surface in cell attachment and growth correlated with the oxygen content
      and mainly the carbonyl content on the surface. Cells were spread more
      extensively and grew faster on the surface with a higher oxygen content.

PMID- 10896046
TI  - Hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA) copolymers for cell
      microencapsulation: effect of HEMA purity.
AB  - Thermoplastic copolymers of 2-hydroxyethyl methacrylate (HEMA) and methyl
      methacrylate (MMA) (molar ratio: 75/25 HEMA-MMA) were synthesized using HEMA
      containing different amounts of ethylene glycol dimethacrylate (EGDMA) to
      investigate their suitability for cell microencapsulation. Pure HEMA (0.0% EGDMA)
      was obtained with preparative chromatography to prepare a linear copolymer.
      Microcapsules (with a diameter of 300-400 microm) were readily made with the
      copolymers by interfacial precipitation. Smaller and more transparent capsules
      were obtained using the copolymer prepared from purer HEMA. Chinese hamster ovary
      (CHO) fibroblasts, as model cells, were microencapsulated in the linear
      copolymer. The CHO cells survived the microencapsulation process and the
      metabolic activity of the encapsulated cells increased within the 14 days
      observation period.

PMID- 10896047
TI  - Electrochemical behavior and differential pulse polarographic determination of
      piperacillin sodium.
AB  - In an aqueous piperacillin sodium solution, a well-defined single wave or single
      peak was observed by direct current (DC) polarography or differential pulse
      polarography (DPP). The peak potential change per pH unit was -54 mV in the
      phosphate buffer at 18 degrees C, which indicated that protons were involved in
      the electrochemical reduction of the 2,3-dioxopiperazine moiety of piperacillin
      sodium with a H+/e- ratio of one. Using a phosphate buffer of pH 4.3, the 1.0 x
      10(-7) M piperacillin sodium single peak could be determined by DPP with relative
      standard deviation of 1.6% (n=3). Piperacillin sodium could be analyzed without
      interference from penicillin G-potassium, which enabled the employment of DPP as
      a fast and simple technique for monitoring the synthetic process of the
      antibiotic.

PMID- 10896048
TI  - A concise synthetic pathway for trans-metanicotine analogues.
AB  - A convenient pathway for synthesis of trans-metanicotine analogues was developed.
      trans-Metanicotine, a subtype (alpha4beta2)-selective ligand for neuronal
      nicotinic acetylcholine receptor, is under clinical phase for Alzheimer's
      disease. Zn-mediated allylation of allyl bromide and acetaldehyde followed by
      Heck reaction with 3-bromopyridine gave 5-pyridin-3-yl-pent-4-en-3-ol (2).
      Tosylation of 5-pyridin-3-yl-pent-4-en-3-ol followed by substitution reaction
      with methylamine in sealed tube gave methyl-(1-methyl-4-pyridin-3-yl-but-3-enyl)
      amine (4) in good yields. Thus, trans-metanicotine analogues modified at the
      alpha-position of the methylamino group with various functional groups can be
      obtained in 4 steps.

PMID- 10896049
TI  - Synthesis and biological evaluation of phosphonate analogues of 1alpha,25
      dihydroxyvitamin D3.
AB  - A new series of phosphonate side chain analogues of 1alpha,25-dihydroxyvitamin D3
      (1) have been synthesized. Antiproliferative activities of theses analogues (8a,b
      and 9a,b) using human keratinocyte cell shows that analogues which have natural A
      ring show higher activity than unnatural A-ring series and almost equally active
      to 1alpha,25-Dihydroxyvitamin D3 (1) at 1 microM level.

PMID- 10896050
TI  - Preparation and determination of structure of L-3-deoxymimosine-containing
      peptides.
AB  - L-3-Deoxymimosine-containing decapeptides were prepared for the development of
      protein tyrosine kinase (PTK) inhibitors. During the preparation of peptides,
      several side products were formed. Identification and determination of major
      peptides generated were reported.

PMID- 10896051
TI  - Synthesis and biological activity of conformationally controlled 2-PAM
      derivatives.
AB  - A series of conformationally controlled 2-PAM derivatives were prepared from 2
      acetylpyridine and 2,3-pyrido[b]cycloalkenones in two steps and their
      reactivities towards parathion poisoned AChE were evaluated. The most planar 2,3
      pyrido[b]cyclohexanone oxime methiodide showed an activity comparable to 2-PAM
      implying E-syn is that the most active conformation of 2-PAM in the biological
      system.

PMID- 10896052
TI  - Enantioselective preparation of metoprolol and its major metabolites.
AB  - To obtain the standard compounds of metoprolol for a pharmacokinetic study, a
      convenient synthetic procedure to prepare enantiomers of metoprolol (3a) and its
      major metabolites, 2-4-(2-hydroxy-3-isopropylamino)propoxyphenylethanol (3b) and
      4-(2-hydroxy-3-isopropylamino)propoxyphenylacetic acid (4), was developed from
      their respective starting materials, 4-(2-methoxyethyl)phenol (1a), 4-(2
      hydroxyethyl)phenol (1b) and methyl 4-hydroxyphenylacetate (1c). These phenolic
      compounds (1a, b, c) were converted in situ to their corresponding phenoxides
      with sodium hydroxide treatment followed by (R)- or (S)-epichlorohydrin
      treatment. The resulting epoxides 2 were transformed to 3 through reaction with
      isopropylamine. Ester 3c was hydrolyzed to the metabolite 4. Measured using the
      HPLC method on chiral column without any derivatization, the optical purity of
      enantiomers of metoprolol and o-demethylated metabolite 3b ranged between 96-99%
      ee and that of enantiomers of carboxylic acid metabolite 4 ranged 91% ee.

PMID- 10896053
TI  - Chiral separation of the enantiomers of metoprolol and its metabolites by high
      performance liquid chromatography.
AB  - (1'R, 2R)-, (1'R, 2S)-, (1'S, 2R)- and (1'S, 2S)-alpha-hydroxymetoprolol; (2R)-
      and (2S)-O-desmethylmetoprolol; and (2R)- and (2S)-metoprolol acid are major
      metabolites of (2R)-and (2S)-metoprolol, beta-adrenergic antagonist. The focus of
      most chiral separation methods until now has been on determination of the
      enantiomeric parent drug. However, it is just as important to be able to follow
      the metabolism of the enantiomers and their possible chiral metabolites.
      Therefore, for the study of stereoselective metabolism and pharmacokinetics of
      metoprolol, the chiral separation of the enantiomers of metoprolol and its
      metabolites has been investigated using four chiral stationary phases, i.e.,
      Chiralcel OD, Chiral-AGP, Cyclobond I and Sumichiral OA-4900 columns. Metoprolol
      acid was resolved only by Sumichiral OA-4900. Chiralcel OD provided the highest
      separation factor and resolution value for metoprolol and O-desmethylmetoprolol
      and partially resolved the four stereoisomers of alpha-hydroxymetoprolol.
      Diastereomeric alpha-hydroxymetoprolols were resolved using the coupled column
      chromatographic system of two chiral stationary phases, Sumichiral OA-4900 column
      and Chiralcel OD column.

PMID- 10896054
TI  - Isolation of luteolin 7-O-rutinoside and esculetin with potential antioxidant
      activity from the aerial parts of Artemisia montana.
AB  - The antioxidant activity of Artemisia montana was determined by measuring the
      radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and
      inhibitory activity against free radical generation of hepatocytes (AC2F). The
      methanol extract of A. montana showed strong radical scavenging activity at a
      concentration of 10.1 microg/ml, and thus fractionated by solvent extraction.
      Esculetin and luteolin 7-O-rutinoside (scolymoside) were isolated as the active
      principles from the EtOAc and Interphase fractions, respectively. The antioxidant
      activity of these compounds were comparable to that of L-ascorbic acid.

PMID- 10896055
TI  - Immunomodulating activity of a polysaccharide isolated from Mori Cortex Radicis.
AB  - The immunomodulating activity of a polysaccharide isolated from Morus alba (PMA)
      root bark was examined in murine splenic lymphocytes. PMA enhanced proliferation
      of splenic lymphocytes in a synergistic manner in the presence of mitogens.
      However, PMA suppressed primary IgM antibody production from B cells, which was
      activated with lipopolysaccharide, a polyclonal activator, or immunized with a T
      cell dependent antigen sheep red blood cells. Our observations showed that the
      immunomodulating activity of PMA increased lymphocyte proliferation and that PMA
      decreased antibody production from B cells, which was distinct from those of
      other plant-originated polysaccharides.

PMID- 10896056
TI  - Aromatase inhibitors from Isodon excisus var. coreanus.
AB  - The diethyl ether extract of Isodon excisus var. coreanus exhibited significant
      inhibitory activity in aromatase assay. Bioactivity-guided fractionation of the
      extract led to the isolation of three active compounds: inflexin (ent-1alpha
      hydroxy-3beta,6a-diacetoxykaur-16-en-11,15-dione ) (1), ursolic acid (2), and
      ursolic acid 3-O-acetate (3).

PMID- 10896057
TI  - Establishment of a high-throughput screening system for caspase-3 inhibitors.
AB  - In most tissues, apoptosis plays a pivotal role in normal development and for
      regulating cell number, thus inappropriate apoptosis underlies a variety of
      diseases. Caspase-3 is one of a family of caspases that are mainly involved in
      the apoptotic signal transduction pathway, where caspase-3 acts as an effect
      molecule to proteolytically cleave intracellular substrates that are necessary
      for maintaining cell survival. Recent evidences show that apoptotic cell death
      can be blocked by inhibiting caspase-3, suggesting its inhibitors have potential
      to be therapeutic drugs for the diseases related with inappropriate apoptosis. We
      have established a screening system to search caspase-3 inhibitors from chemical
      libraries stocked in our institute. The enzyme assay is configured entirely in 96
      well format, which is easily adapted for high throughput screening. Before
      performing mass screening, 80 in-house compounds were screened as a preliminary
      experiment, and we found that morin hydrate inhibited caspase-3 by 66.4% at the
      final concentration of 20 microM.

PMID- 10896058
TI  - A mouse thymic stromal cell line producing macrophage-colony stimulating factor
      and interleukin-6.
AB  - A thymic stromal cell line, TFGD, was established from a thymic tumor mass
      developed spontaneously in p53 knock out mouse, and was found to produce
      cytokines that could induce bone marrow hematopoietic stem cells (HSCs) to
      differentiate into macrophages. The cytokines produced by the TFGD line were
      assessed by immunoassays. High level of macrophage-colony stimulating factor (M
      CSF) and interleukin (IL)-6 was detected in the TFGD-culture supernatant, whereas
      granulocyte/macrophage-colony stimulating factor (GM-CSF), IL-3, IL-4, IL-5, IL
      13, or interferon (IFN)-gamma was undetectable. Blocking experiments showed that
      anti-M-CSF monoclonal antibody could neutralize the differentiation-inducing
      activity shown by the TFGD-culture supernatant. Dot blot analysis of the total
      RNA isolated from the cultured fetal thymic stromal cells showed that M-CSF
      transcripts were expressed in the normal thymus. These observations, together
      with the earlier finding that M-CSF plus IL-6 is the optimal combination of
      cytokines for the induction of macrophage differentiation from HSCs in vitro, may
      indicate that thymic macrophages could be generated within the thymus by
      cytokines involving M-CSF.

PMID- 10896059
TI  - Evaluation of tTA-mediated gene activation system on human cytomegalovirus and
      herpes simplex virus type-1 infections.
AB  - The tetracycline-controlled transactivator (tTA)-mediated gene activation system
      was examined in virus infected cells to determine its role in the control of gene
      expression. In the presence of tTA, the gene expression from the tetO-modified
      minimal promoter was efficiently activated in the uninfected cells, whereas
      essentially no activation was observed from the only minimal promoter without the
      seven direct repeats of 42 bp tetO sequences. However, essentially no activation
      was observed when only the minimal promoter was used, without the seven direct
      repetitions of the 42 bp tetO sequences. On the other hand, in the infected
      cells, a substantial background of beta-glucuronidase expression was detected in
      the absence of tTA, even though tTA stimulated the gene expression by
      approximately 7-fold. This background expression indicates that the sequences
      within or nearby tetO are involved in the background stimulation of the gene
      expression by HCMV and HSV-1. These results suggest that the application of the
      tTA-mediated gene activation system may not be extremely useful for studying the
      biological roles of HCMV and HSV genes in the viral replicative cycles, because
      of the basal activity of the gene expression.

PMID- 10896060
TI  - Inhibitory effects of crude drugs on alpha-glucosidase.
AB  - The inhibitory activity of several crude drugs on alpha-glucosidases, which are
      the key enzymes for carbohydrate digestion and the prevention of diabetic
      complications, was investigated. Several crude drugs including Terminaliae
      Fructus, Mori Cortex Radicis, Caesalpiniae Lignum and Gyrophora esculenta
      potently inhibited maltase and sucrase isolated from rat intestine, while Arecae
      Semen and Corni Fructus remarkably inhibited alpha-amylase. Caesalpiniae Lignum
      and Gyrophora esculenta exhibited significant reductions of blood glucose
      elevation in mice loaded with maltose and sucrose.

PMID- 10896061
TI  - Flying into the post-genome era.

PMID- 10896062
TI  - The next molecule of the year?: Carbon monoxide as a regulator of host
      inflammatory responses.

PMID- 10896063
TI  - Enteral nutrition: the neglected primary therapy of active Crohn's disease.

PMID- 10896064
TI  - Enteral nutrition and corticosteroids in the treatment of acute Crohn's disease
      in children.
AB  - BACKGROUND: The optimal treatment of acute Crohn's disease in children remains
      controversial. In adults, steroid therapy has been shown to be superior to
      exclusive enteral nutrition. However, enteral nutrition is effective at inducing
      a remission in many children with acute Crohn's disease. Steroid usage in
      children has been associated with adverse side effects, particularly with delayed
      growth and pubertal development. METHODS: Randomized clinical trials comparing
      exclusive enteral nutrition with corticosteroids were identified. Two independent
      reviewers extracted data from selected studies. Studies were assessed for
      heterogeneity and relative risks for remission induction with enteral nutrition
      were obtained. Sensitivity analyses were performed in partially randomized
      studies. Estimates were made of the number of studies needed to overturn the
      current result. Other outcome measures were qualitatively assessed. RESULTS: In
      five randomized clinical trials comprising 147 patients, enteral nutrition was as
      effective as corticosteroids at inducing a remission (RR = 0.95 [95% confidence
      interval 0.67, 1.34]). Addition of two further nonrandomized trials did not
      significantly alter the result. A minimum of 10 further studies, equal in size
      and outcome to the largest reported pediatric trial to date (n = 68, RR = 0.84),
      would be required to demonstrate a significant benefit of steroid therapy over
      enteral nutrition. CONCLUSIONS: There is no difference in efficacy between
      enteral nutrition and corticosteroid therapy in the treatment of acute Crohn's
      disease in children. Improved growth and development, without the side effects of
      steroid therapy, make enteral nutrition a better choice for first-line therapy in
      children with active Crohn's disease.

PMID- 10896065
TI  - Lactulose-mannitol intestinal permeability test in children with diarrhea caused
      by rotavirus and cryptosporidium. Diarrhea Working Group, Peru.
AB  - BACKGROUND: The relationship between intestinal permeability and acute secretory
      diarrheal syndromes caused by rotavirus and Cryptosporidium parvum in infants
      less than 36 months of age was studied using the lactulose-mannitol excretion
      assay. METHODS: An oral solution containing 0.4 g/kg lactulose and 0.1 g/kg
      mannitol was administered to 15 infants with rotavirus, 7 with Cryptosporidium
      infection and a control group of 7 with secretory diarrhea admitted to the Oral
      Rehydration Unit of the National Children's Hospital in Lima, Peru. Urinary sugar
      excretion was measured using an enzymatic spectrophotometric method. The ratio of
      urinary excretion of lactulose to mannitol was used to measure intestinal mucosal
      permeability, with higher ratios indicative of increased intestinal permeability.
      Infants in all three groups were retested 20 days after the initial test.
      RESULTS: The (mean +/- SE) lactulose:mannitol (L:M) excretion ratios during the
      acute phase (day 1) of diarrhea in infants with rotavirus or Cryptosporidium and
      control infants were 0.67 +/- 0.1, 0.76 +/- 0.16, and 0.26 +/- 0.04,
      respectively. In the convalescent phase (day 20) the ratios were 0.19 +/- 0.02,
      0.28 +/- 0.05, and 0.29 +/- 0.07, respectively. Significant reductions in L:M
      ratios were noted in rotavirus patients between days 1 and 20 (paired t-test; P <
      0.01), Cryptosporidium patients between days 1 and 20 (paired t-test; P < 0.05),
      and between control subjects on day 1 and rotavirus patients on day 1 and
      Cryptosporidium patients on day 1 (unpaired t-tests; P < 0.05 for both). There
      were no significant differences in control subjects between days 1 and 20,
      control subjects and rotavirus patients on day 20, or control subjects and
      Cryptosporidium patients on day 20. CONCLUSIONS: The results indicate that
      increased intestinal permeability caused by rotavirus or cryptosporidium
      infections in Peruvian infants less than 36 months of age is a significant but
      reversible phenomenon. The temporal relationship observed in the current study
      and the contribution of such alterations in intestinal mucosal integrity to the
      burden of diarrheal disease and the development of malnutrition in developing
      countries is discussed.

PMID- 10896066
TI  - Celiac disease and human leukocyte antigen genotype: accuracy of diagnosis in
      self-diagnosed individuals, dosage effect, and sibling risk.
AB  - BACKGROUND: Celiac disease is an autoimmune disorder of the small intestine
      characterized by intolerance to gluten. Traditionally, diagnosis is made by
      intestinal biopsy. Testing for immunoglobulin (Ig) A endomysial antibodies in the
      serum also is used for diagnosis. Biopsy and serology revert to normal with
      adherence to a gluten-free diet. Often, after an index case is diagnosed,
      siblings with symptoms adhere to a gluten-free diet without biopsy or serologic
      confirmation. More than 90% of patients with celiac disease have the human
      leukocyte antigen (HLA) DQA1*0501-DQB1*0201 genotype. Non-HLA genes also have
      been implicated. METHODS: One hundred ninety-five individuals with confirmed or
      suspected celiac disease were identified in 73 families affected by the disease.
      IgA endomysial antibody testing was performed for all symptomatic family members
      who did not have biopsy-confirmed diagnoses. DNA samples were genotyped at D6S276
      and the HLA class II loci DQA and DQB. RESULTS: At the time sampling was begun in
      families, 88 of 177 (49.7%) individuals were self-diagnosed and adhering to a
      gluten-free diet. Ninety percent (91/101) of confirmed cases (biopsy or serology)
      had at least 1 copy of the DQA1*0501-DQB1*0201 genotype, whereas only 67% (46/69)
      of cases self-diagnosed (adherence to gluten-free diet without confirmation) had
      at least 1 copy. Of confirmed cases, 61% carried two copies of DQB*0201. It is
      estimated that the HLA association and other unlinked genes contribute
      approximately equally to the sibling risk of celiac disease. CONCLUSIONS: A
      dosage effect of DQB1*0201 may be associated with an increased risk of celiac
      disease. Self-diagnosis of celiac disease is as common as confirmed diagnosis in
      families in the United States. Diagnosis of celiac disease on the basis of
      clinical response to gluten restriction is inaccurate. With long-term adherence
      to a gluten-free diet, serologic test results are likely to be negative. Based on
      HLA genotype, approximately one third of self-diagnosed individuals are unlikely
      to have celiac disease. However, it is not possible to determine which
      individuals consuming a gluten-free diet have the disease. Therefore, before
      starting a gluten-free diet, serologic screening and biopsy confirmation are
      necessary.

PMID- 10896067
TI  - Direct measurement of pancreatic enzymes after stimulation with secretin versus
      secretin plus cholecystokinin.
AB  - BACKGROUND: Direct measurement of pancreatic enzymes after administration of
      pancreatic secretagogues is the gold standard in the assessment of exocrine
      pancreatic function. Recent experience at the authors' institution showed that
      endoscopic collection of pancreatic secretions 5, 10, and 15 minutes after
      intravenous administration of secretin is useful in screening for pancreatic
      insufficiency. Concomitant administration of intravenous cholecystokinin has been
      a subject of debate. The purpose of this study was to compare pancreatic enzyme
      levels after administration of secretin versus secretin plus cholecystokinin and
      to validate the timing of collection of duodenal fluid. METHODS: A prospective,
      randomized, double-blind study was conducted from September 1997 through
      September 1998. Patients scheduled for pancreatic enzyme sampling were randomly
      assigned to receive intravenous secretin (2 U/kg) plus placebo (group 1) or
      intravenous secretin (2 U/kg) plus cholecystokinin (0.02 microg/kg [Group 2]).
      Duodenal fluid was collected 5, 10, and 15 minutes later and placed in dry ice.
      Samples were measured for the levels of trypsin, amylase, lipase, and
      chymotrypsin. RESULTS: Twenty patients were assigned to each group. The age range
      was similar in both groups: 12 months to 16 years, 8 months in group 1 (median,
      2.1 years) and 15 months to 13 years, 7 months in group 2 (median, 2.5 years).
      Group 2 had a greater number of patients with all four enzymes at normal levels
      during at least one of the time points, 75% versus 50% (P = 0.102). The
      difference in enzyme levels at the 5-, 10-, and 15-minute collections was
      statistically significant. For all four enzymes in both groups, values varied
      from highest to lowest with time (P = 0.0001). The enzyme levels at 10 minutes
      were close to the enzyme levels at 5 minutes; the lowest values occurred at 15
      minutes. CONCLUSIONS: Higher pancreatic enzyme levels were obtained after
      administration of secretin plus cholecystokinin, although the trend did not reach
      statistical significance. Pancreatic enzyme levels are highest at 5 and 10
      minutes, indicating that collections of duodenal fluid should be completed within
      10 minutes of the administration of the secretagogues.

PMID- 10896068
TI  - Growth, body composition, and nutritional status in children and adolescents with
      Crohn's disease.
AB  - OBJECTIVE: To examine growth, body composition, and nutritional status in a large
      sample of children, adolescents, and young adults with Crohn's disease (CD).
      METHODS: One hundred thirty-two subjects (48 females) with CD, aged 5 to 25
      years, and 66 healthy control subjects (37 females) of similar age. Growth,
      nutritional status, and body composition were measured by anthropometry and dual
      energy x-ray absorptiometry. Genetic potential of linear growth was predicted
      using the adjusted heights of Himes et al. Pubertal status and skeletal age were
      assessed. Average Pediatric Crohn's Disease Activity Index (PCDAI) and lifetime
      steroid exposure (in milligrams per day) were obtained from medical charts. The
      variables were examined in relation to gender and measures of disease activity.
      RESULTS: Males and females with CD did not differ by age, disease duration, or
      PCDAI. Males with CD had significantly lower values for growth and nutritional
      status than control subjects (z-scores for weight: -0.66 +/- 1.18 vs. 0.26 +/-
      0.95, P = 0.00002; height -0.81 +/- 1.14 vs. 0.28 +/- 0.93, P = 0.00001; adjusted
      height -1.05 +/- 1.03 vs. 0.40 +/- 1.03, P = 0.00001) and delayed skeletal age of
      0.9 +/- 1.6 years. Impaired linear growth in the males was present regardless of
      pubertal stage. Associations between disease severity indicators and growth
      parameters were more consistent for females. CONCLUSIONS: Crohn's disease is
      associated with impaired growth. Despite similarities in disease duration,
      activity, and lifetime steroid exposure, growth in males was more impaired.
      Gender may confer risk for impaired growth in CD.

PMID- 10896069
TI  - Deep sedation with inhaled sevoflurane for pediatric outpatient gastrointestinal
      endoscopy.
AB  - BACKGROUND: Sevoflurane is an inhaled anesthetic agent with ideal properties for
      achieving deep sedation during pediatric outpatient gastrointestinal endoscopy.
      This is a comparison of experience with this gas and other sedation methods used
      in the authors' hospital. METHODS: Retrospective chart review and statistical
      analysis of data from children receiving inhaled sevoflurane administered by an
      anesthesiologist through laryngeal insufflation, intravenous propofol, or
      intravenous midazolam-fentanyl-ketamine in any combination to achieve deep
      sedation for outpatient gastrointestinal endoscopy. Anesthesia was administered
      in a dedicated procedure room. The intravenous drugs were administered by
      pediatric intensivists in the intensive care unit. The same endoscopist performed
      all the procedures. RESULTS: A total of 248 procedures were reviewed (midazolam
      fentanyl-ketamine 67, propofol 114, and sevoflurane 67). All patients were
      adequately sedated with sevoflurane, and no intravenous access was required. Time
      (in minutes) to awakening (midazolam-fentanyl-ketamine 47.15, propofol 36.12,
      sevoflurane 5.70), discharge (midazolam-fentanyl-ketamine 141.99, propofol 91.20,
      sevoflurane 53.34), and total time, including induction and procedure (midazolam
      fentanyl-ketamine 163.97, propofol 119.40, sevoflurane 73.93), were significantly
      lower for sevoflurane (P < 0.01). The complication rate for sevoflurane (4.5%)
      was lower (P < 0.05) than for midazolam-fentanyl-ketamine (13.4%) and for
      propofol (17.5%). Charges for room use and medications were also lower for
      sevoflurane (P < 0.01). The total charges for sedation (U.S.$) were comparable
      for sevoflurane (688.10) and propofol (723.08) but were higher for midazolam
      fentanyl-ketamine (855.10, P < 0.01). CONCLUSIONS: Deep sedation with inhaled
      sevoflurane for pediatric outpatient gastrointestinal endoscopy is as safe as
      conventional sedation techniques, potentially less expensive, increases endoscopy
      unit productivity, and eliminates the inconvenience associated with obtaining
      intravenous access in children.

PMID- 10896070
TI  - Treatment of recurrent abdominal pain: components analysis of four treatment
      protocols.
AB  - BACKGROUND: Recurrent abdominal pain (RAP) affects up to 34% of the world's
      population of children. Medical management has been limited, but behavioral
      strategies have been shown to be effective. In this study several components of
      published treatment protocols were adapted and/or improved and then compared
      using a pretest-posttest control group design. METHODS: Sixty-four children and
      teenagers (mean age, 9.75 +/- 2.46 years) with diagnosed recurrent abdominal pain
      were randomly assigned to four groups: 1) fiber-only comparison group; 2) fiber
      and biofeedback-assisted cultivated low arousal; 3) fiber, biofeedback, and
      cognitive-behavioral interventions; and 4) fiber, biofeedback, cognitive
      behavioral, and parental support. Participants were treated over 8 weeks in
      individual sessions. Biofeedback was supplied using small thermal devices.
      RESULTS: All groups showed improvement in self-reported pain, even the fiber-only
      comparison group; however, the active treatment groups showed significantly more
      improvement before and after than the fiber-only comparison group (fiber only
      comparison group pain reduction at 79%; fiber and biofeedback at 100%; fiber,
      biofeedback, and cognitive-behavioral at 94%; fiber, biofeedback, cognitive
      behavioral, and parental support at 93%). CONCLUSIONS: This suggests that any of
      the active treatment protocols assessed in this investigation work better than
      established treatments that have been reported in the literature. Because the
      addition of cognitive and parental support components did not seem to increase
      treatment effectiveness, it is concluded that increased fiber with biofeedback
      assisted cultivated low arousal was effective and efficient as a treatment
      modality.

PMID- 10896071
TI  - Iron-deficiency anemia associated with Helicobacter pylori gastritis.
AB  - BACKGROUND: Recent studies have suggested an association of Helicobacter pylori
      and iron-deficiency anemia (IDA). This is a report of six cases of IDA associated
      with H. pylori gastritis. METHODS: Six patients with IDA were studied (5 boys and
      1 girl; mean age 13.6 years; range 13-15 years). Five had a medical history of
      long-standing IDA and of oral iron supplementation at outpatient clinics. The
      anemia recurred after the iron therapy had been discontinued. The sixth patient
      was admitted to the hospital with severe IDA. An extensive work-up was ordered
      that included technetium-99m (99mTc) scans for Meckel's diverticulum, total
      colonoscopy, and gastrointestinal endoscopy. After biopsy-based H. pylori test
      results were confirmed to be positive, anti-H. pylori therapy consisting of
      lansoprazole, clarithromycin, and metronidazole was administered for 2 weeks with
      no iron supplementation. The hematologic profile and iron status were assessed
      periodically after the end of the eradication regimen. RESULTS: Upper
      gastrointestinal endoscopy revealed a marked antral nodularity but no evidence of
      bleeding lesions in all the patients. Given the histology and the fact that rapid
      urease test results were positive, chronic active gastritis with H. pylori was
      diagnosed in all these cases. H. pylori was successfully eradicated in all the
      patients. There was no evidence of IDA in any of the follow-up examinations
      between 27 and 50 months after anti-H. pylori therapy. CONCLUSIONS: H. pylori
      infection may be involved in cases of IDA of unknown origin, and the eradication
      of H. pylori can be associated with the resolution of anemia.

PMID- 10896072
TI  - Molybdenum supplementation in phenylketonuria diets: adequate in early infancy?
AB  - BACKGROUND: Molybdenum concentrations in formulas exceed those in human milk by
      far. Infants with phenylketonuria require semisynthetic phenylalanine-restricted
      diets. Because these diets are presently supplemented with molybdenum, a study
      was conducted to determine whether retention and plasma concentration in the
      recipients are equivalent to those of healthy breast-fed infants. METHODS:
      Balance and plasma studies were conducted in healthy breast-fed infants (n = 17)
      and in patients with phenylketonuria (n = 4) at the age of 4 weeks, and the
      plasma investigations were repeated at the ages of 4 and 12 months. The samples
      were analyzed by atomic absorption spectroscopy (balance studies) and high
      resolution inductively coupled plasma mass spectrometry (plasma). RESULTS:
      Molybdenum intake and retention in all infants with phenylketonuria were more
      than 18 times those of breast-fed infants. The plasma concentrations reflected
      these differences. A median of 0.04 microg/l was assessed in breast-fed infants
      at 4 weeks and less than 0.02 microg/l at 4 months of age. Comparative results of
      infants with phenylketonuria were 2.9 microg/l and 2.5 microg/l, respectively.
      There were no significant differences between the groups at 12 months of age.
      CONCLUSIONS: The phenylketonuria diets investigated showed excessive retention
      and plasma concentrations of the essential trace element molybdenum in early
      infancy. In view of these findings, the present practice of molybdenum
      fortification should be revised.

PMID- 10896073
TI  - Sulfomucins in Helicobacter pylori-associated chronic gastritis in children: is
      this incipient intestinal metaplasia?
AB  - BACKGROUND: Little is known about early stages of intestinal metaplastic in
      chronic gastritis. The purpose of this study was to determine the presence of
      sulfated mucosubstances hence most probably intestinal metaplasia, in isolated
      cells of surface gastric pits, and glands in pediatric patients with Helicobacter
      pylori-associated chronic gastritis. METHODS: Participants were nine patients
      (nine different biopsies; mean age 11.5 years, range 3-16 years) with sulfomucin
      containing cells evident in the gastric biopsy specimen. Eight of the patients
      were selected from a group of 15 patients with histologically documented H.
      pylori-associated chronic gastritis in whom the utility of the Sydney system was
      being tested. RESULTS: Symptoms and endoscopic findings of H. pylori-associated
      chronic gastritis were the same regardless of the presence or absence of
      sulfomucin-containing cells. On hematoxylin and eosin stained tissues, neither
      intestinal metaplasia nor atrophy was apparent. However, periodic acid-Schiff
      (PAS)-alcian blue (pH 1.0) stain revealed the presence of sulfated mucosubstances
      in isolated cells of gastric pits and glands in the nine patients. CONCLUSIONS:
      This finding may represent a "minimal" form of incomplete intestinal metaplasia
      (type III). Because the nine patients had been untreated, the change is probably
      reversible. Two follow-up biopsies in patients in whom H. pylori had been treated
      and eradicated showed absence of sulfated mucins. Although these findings cannot
      be regarded as fully developed type III intestinal metaplasia, it is possible
      that left untreated, the alteration may persist and evolve into some other
      complication. This conclusion justifies follow-up of these patients.

PMID- 10896074
TI  - Dieulafoy's lesion in an infant: a rare cause of massive gastrointestinal
      bleeding.

PMID- 10896075
TI  - Gastrointestinal dysfunction associated with syringomyelia and hydromyelia.

PMID- 10896076
TI  - Infantile esophageal intramural pseudodiverticulosis.

PMID- 10896077
TI  - Perianal Crohn's disease in infancy.

PMID- 10896078
TI  - Idiopathic perforation of the bile duct in an infant.

PMID- 10896080
TI  - Clinical quiz. Crohn's disease.

PMID- 10896079
TI  - Refractory enteric amebiasis in pediatric patients with acute graft-versus-host
      disease after allogeneic bone marrow transplantation.

PMID- 10896081
TI  - Iron and hepatitis C.

PMID- 10896082
TI  - Wilson disease: diagnostic dilemmas?

PMID- 10896083
TI  - Use of beta-blockers for primary prophylaxis of variceal bleeding.

PMID- 10896084
TI  - Long-term effect of early vitamin-D supplementation on bone mineral status in
      prematurely born infants.

PMID- 10896085
TI  - Continued cisapride prescription.

PMID- 10896086
TI  - The Euro-Growth Study: why, who, and how.
AB  - BACKGROUND: Assessment of growth is important in health management of infants and
      children. Evaluation of growth performance requires anthropometric measurements,
      with proper interpretation depending on the use of appropriate references. Europe
      specific growth references have not been available. The purpose of the present
      study was to generate such references for infants and children from birth to 3
      years of age. The study was further intended to assess the influence of nutrition
      and lifestyle factors on growth. METHODS: The Euro-Growth Study was designed as a
      multicenter longitudinal cohort study. This report describes the study design,
      the sample (cohort), and the methods used. Quality control measures included
      standardized measurement techniques with ongoing cross-sectional and longitudinal
      consistency checks. Selectivity in participation and discontinuation and
      reproducibility of data over time were evaluated. RESULTS: Of 2,245 infants who
      were enrolled in the study at 22 study sites in 11 countries, 1,746 (78%)
      provided longitudinal data until 12 months of age, 1,205 (57%) until 24 months of
      age, and 1071 (48%) until 36 months of age. Anthropometric measurements were
      performed on 21,773 occasions. As a result of cross-sectional and longitudinal
      data checks, 209 data points (0.09% of all data points) were rejected. Comparison
      of participants's demographic data with those of nonparticipating local subjects
      indicated that the cohort was selective in maternal age (higher), maternal
      education level (higher), household location, and family structure. The
      withdrawal rate during the study was low (24%), and withdrawals occurred at
      random. Analysis of reproducibility over time resulted in the elimination of the
      data from one study site. CONCLUSION: The Euro-Growth Study provided longitudinal
      growth data from a large cohort of normal European children. Because of the
      chosen sampling method, the study cohort ws somewhat selective relative to the
      local background population. Internal validity was satisfactory in that the
      reproducibility of anthropometric measurements was high in 21 sites and the
      withdrawal rate was low and random.

PMID- 10896087
TI  - Euro-Growth references for length, weight, and body circumferences. Euro-Growth
      Study Group.
AB  - BACKGROUND: Several concerns have been raised by World Health Organization (WHO)
      expert groups regarding the adequacy of currently existing growth references,
      including those currently supported by WHO. As part of a concerted action of the
      European Union, new references were developed that were based on a well-defined
      sample of the European population and were compared with existing references.
      METHODS: During the longitudinal, observational multicenter study, anthropometric
      measurements using standardized methodology were performed in 2,245 children
      between 1 and 36 months of age, and sex- and age-specific growth references for
      recumbent length, weight, mid-upper arm, thigh, and calf circumferences were
      developed. RESULTS: The validity of the curve-fitting programs was demonstrated
      by comparing the selected sex-specific percentile distributions for all indices
      with the smoothed references. Comparison with the National Center for Health
      Statistics (NCHS)-WHO references for length and weight for age indicated that the
      -2 z-score value of the WHO reference as cutoff value shows that a substantial
      part of the children with suspected failure to thrive should be classified as
      normal. The references also indicate that the mid-upper arm circumference is age
      and sex dependent and that a single cutoff value for children less than 5 years
      of age should no longer be used. Mid-parental height was the best single
      predictor of recumbent length until 36 months of age. CONCLUSIONS: The Euro
      Growth references that were developed reflect growth of a well-defined, large
      cohort of healthy infants and can be used for international comparisons.

PMID- 10896088
TI  - Euro-Growth references on increments in length, weight, and head and arm
      circumferences during the first 3 years of life. Euro-Growth Study Group.
AB  - BACKGROUND: Reliable assessment of growth performance of infants and young
      children requires reference data increments. Available increment references are
      based on data fitted to mathematical models, a process that diminishes variation
      in increment values. METHODS: Fully longitudinal data from the multicenter Euro
      Growth Study (21 study sites: n = 2145 children) were used to develop sex
      specific percentiles for increments in length, weight, and head and mid-upper arm
      circumferences for selected intervals during the first 36 months of life.
      Increments (per unit of time) were calculated for 2-, 3- and 6-month intervals
      from birth to 12 months of age and for 6-month intervals from 12 to 36 months of
      age. Weight increments were also calculated for 1-month intervals from birth to 6
      months of age. The influence of sex, mid-parental height, and study site was
      determined using analysis of covariance. Comparison with other references was
      accomplished using percentile values. RESULTS: Mean and standard deviation values
      as well as selected percentiles (P; P3, P5, P10, P25, P50, P75, P90, P95, and
      P97) of increments are presented. Length increments of boys were higher than
      those of girls until 5 months of age but tended to be lower thereafter. Weight
      increments of boys were higher until 9 months of age. Sex, mid-parental height,
      and study site explained only between 2% and 13% of the variances of increments.
      Mean increments were comparable but P10 and P90 substantially differed from
      published data. CONCLUSIONS: The new Euro-Growth references for increments in
      length, weight, and head and mid-upper arm circumferences provide tools for
      health workers that should be useful in screening for adequacy of growth during
      the first 3 years of life.

PMID- 10896089
TI  - Euro-Growth references for body mass index and weight for length. Euro-Growth
      Study Group.
AB  - BACKGROUND: Fully longitudinal data from the multicenter Euro-Growth study (21
      study sites; n = 2145 children) were used to develop sex-specific percentiles and
      Z-scores for body mass index (BMI) and weight for length (WfL) during the first
      36 months of life. METHODS: Smoothed percentile curves for BMI against age were
      constructed and checked against raw percentiles. Smoothed percentile curves for
      WfL were constructed according to established procedures and were checked against
      raw percentiles. The relation of BMI with length and of WfL with age was
      examined. The relation between BMI and WfL was tested using z-scores of each. The
      influence of gender, geographic location (study site), and genetic factors on BMI
      and WfL was examined. Finally, the new references for BMI and WfL were compared
      with other published references. RESULTS: Selected percentiles (P; P3, P5, P10,
      P25, P50, P75, P90, P95, and P97) for BMI showed a sharp increase from 1 to 6
      months of age and a gradual decline between 12 and 36 months. Smoothed
      percentiles for WfL showed only small deviations from raw percentiles. BMI was
      found to be essentially independent of length, whereas WfL showed some degree of
      dependence on age. Values for BMI and WfL showed very good agreement, except at
      the extremes of the age range. A modest degree of influence of geographic
      location on BMI and WfL was found. Correlations with parental BMI and WfL were
      very weak, however. Comparison with the National Center for Health Statistics
      (NCHS) references showed the latter to have a narrower range of values.
      CONCLUSIONS: The new Euro-Growth references for BMI and WfL provide improved
      tools for health workers and researchers dealing with childhood obesity.

PMID- 10896090
TI  - Euro-Growth references for breast-fed boys and girls: influence of breast-feeding
      and solids on growth until 36 months of age. Euro-Growth Study Group.
AB  - BACKGROUND: The World Health Organization (WHO) recommends exclusive breast
      feeding during the first 4 to 6 months of life, but limited information is
      available regarding the growth performance of infants fed according to the
      recommendation. The present study used data from the Euro-Growth study to
      determine the growth of breast-fed European infants who did or did not receive
      solids from an early age, in comparison with growth of infants who were fed by
      other modes. METHODS: There were 319 infants who were exclusively breast-fed
      according to the WHO recommendations for at least 4 to 5 months, and 185 infants
      who were breast fed but received solids (but no formula) from an early age. There
      were 1,509 infants who were fed in a variety of ways, which included breast
      feeding during the early months of life in the majority (65%) of infants.
      Anthropometric data were available from birth to 36 months of age. Growth of the
      two groups of breast-fed infants was assessed by comparing z-scores of length,
      weight, and body mass index with those of the group fed by other means.
      Furthermore, multiple regression analysis was used to assess the influence on
      increment in length and weight of the duration of breast-feeding and the age at
      which solids were introduced. Euro-Growth references for breast-fed boys and
      girls were developed and compared with the National Center for Health Statistics
      (NCHS)-WHO and Euro-Growth references. RESULTS: The pattern of growth of children
      who were fed according to the WHO recommendations showed higher weight during the
      first 2 to 3 months of life and lower weight and length from 6 to 12 months.
      Between 12 and 36 months of age, differences between groups were small and
      clinically nonrelevant. Duration of breast-feeding was negatively correlated with
      increment in length and weight until 12 and 24 months but not until 36 months of
      age. The influence of duration of breast-feeding was much weaker than that of mid
      parental height. The mean and standard deviation z-scores of the Euro-Growth
      references for weight of breast-fed infants deviate substantially from the NCHS
      WHO references during the first 6 months of life in particular. The mean and
      standard deviation z-scores for length and weight of breast-fed children were
      close to the Euro-Growth references. CONCLUSION: The Euro-Growth references may
      be used to monitor length, weight, body mass index, and body circumferences of
      children who are fed according to WHO recommendations. The additional references,
      which were developed for breast-fed boys and girls, will be useful in view of the
      commitment of WHO to the collection of data for the development of a new
      international growth reference.

PMID- 10896091
TI  - Iodine supply in children from different european areas: the Euro-growth study.
      Committee for the Study of Iodine Supply in European Children.
AB  - BACKGROUND: In many areas of Europe iodine deficiency disorders still exist.
      Urinary iodine excretion is a valuable tool in characterizing the iodine supply
      of a population. However, there is a continuing discussion on the most
      appropriate parameter to measure urinary iodine excretion. METHODS: In 247
      children (ages 3-5 years) from six European centers, spot urine samples were
      analyzed for urinary iodine concentration and urinary iodine-creatinine ratio.
      RESULTS: The median values of urinary iodine concentration from the six centers
      were very similar (90-106 microg/l) corresponding to a normal or marginal iodine
      supply according to the criteria of the World Health Organization. However, the
      median values of the urinary iodine-creatinine ratio from the six centers
      differed significantly (143-445 microg/g, P < 0.001). The different results of
      the two urinary parameters to assess urinary iodine supply were due to large
      significant differences in the urinary creatinine concentration reported by the
      various centers, which probably reflect marked differences in water intake.
      CONCLUSIONS: Iodine deficiency is still a significant health problem in many
      European countries. In comparable and homogeneous population subgroups (even from
      different countries), the urinary iodine-creatinine ratio appears to be a much
      better parameter for assessing iodine supply than urinary iodine concentration.

PMID- 10896092
TI  - Patterns of milk and food intake in infants from birth to age 36 months: the Euro
      growth study.
AB  - BACKGROUND: Little detailed information is available on feeding practices of
      infants in Europe. The Euro-Growth Study is a longitudinal, observational,
      multicenter study of milk feeding, the introduction of complementary solid foods,
      and vitamin and mineral supplementation. Current practice is compared with
      international feeding recommendations. METHOD: Healthy term infants (n = 2,245)
      were recruited at birth or during the first month of life. Dietary records were
      completed at the ages 1, 2, 3, 4, 5, 6, 9, 12, 18, 24, 30, and 36 months by
      semiquantitative dietary recall. RESULTS: At the age of I month, 52% of the
      infants were exclusively breast fed and 26% were exclusively formula fed. At the
      age of 9 months, 18% of infants were fed only cow's milk. At the ages of 3, 4,
      and 5 months, 50%, 67%, and 95% of infants were fed solid foods, respectively.
      CONCLUSIONS: Feeding practices vary considerably throughout Europe. High rates of
      breast-feeding initiation are found in Umea, Sweden, and in Athens, Greece; and
      low rates in Dublin, Ireland, in Toulouse, France, and in Glasgow, United
      Kingdom. The use of cow's milk as the main milk drink before the age of 12 months
      is still common in certain European centers.

PMID- 10896093
TI  - Statistical methods in epidemiology. v. Towards an understanding of the kappa
      coefficient.
AB  - PURPOSE: This paper introduces readers to the problem of measuring interrater
      agreement in observer variation studies. The most usual statistic to quote is the
      kappa coefficient which measures agreement having corrected for chance. METHOD:
      The kappa coefficient for measuring agreement between two observers is
      introduced. Some pointers are given to determining sample size estimation.
      RESULTS: Some properties of the kappa coefficient are illustrated by taking
      examples from the author's teaching experiences. CONCLUSION: The kappa
      coefficient is recommended for measuring agreement in observer variation studies.

PMID- 10896094
TI  - Declines in physical functioning attributable to hip fracture among older people:
      a follow-up study of case-control participants.
AB  - PURPOSE: To identify declines in physical functioning, directly attributable to
      the effects of hip fracture. METHODS: A follow-up study of participants in a case
      control study was conducted in Auckland, New Zealand, between 1993 and 1996. Nine
      hundred and eleven randomly selected older people with a hip fracture at the time
      of the initial interview (cases) and 910 randomly selected older people, without
      hip fracture (controls), were invited to participate in the study. Two year
      changes in physical functioning, defined in terms of self-reported mobility,
      functional dependence and physical activity were examined. RESULTS: Data from the
      survivors (572 cases and 756 controls) showed that, after controlling for pre
      existing chronic medical conditions and disabilities, cases were 4.2 times more
      likely than controls to be community immobile (95% confidence interval (CI) 2.8
      6.2, p < 0.001) and 2.6 times more likely to be functionally dependent (95% CI
      1.7-4.1, p < 0.001). Cases were also spending less hours per day on their feet
      (2.9) compared with controls (3.5) (F1,1211 = 55.7, p < 0.001). CONCLUSIONS: Hip
      fractures are associated with dramatic declines in physical functioning at two
      years, independent of the effects of increasing age, pre-existing medical
      conditions and disabilities.

PMID- 10896095
TI  - Health promotion needs of young people with disabilities--a population study.
AB  - PURPOSE: Few research studies have sought to examine the health promotion needs
      of young people with disabilities. This paper reports the association between
      self-reported disability and various health behaviours (tobacco and alcohol use,
      physical activity, sedentary activities) psycho-social outcomes and school
      satisfaction. METHOD: Cluster stratified random sampling was combined with a
      cross-sectional descriptive design to obtain 3918 school students attending year
      6 (primary school), year 8 and year 10 (high school) throughout New South Wales
      (Australia), to complete a self-administered questionnaire. RESULTS: The
      prevalence of self-reported disability among this student sample was 5.8%. The
      most frequently reported disabilities were physical, sensory and learning
      disabilities. Students with disabilities reported similar health and educational
      outcomes as their able-bodied peers. However, they also reported lower levels of
      school satisfaction, greater voluntary absenteeism and were more likely to get
      drunk or smoke cigarettes. Students with disabilities reported higher levels of
      psycho-social distress. They were also as physically active as other students,
      but also spent more time engaged in sedentary activities. CONCLUSION: Students
      with self-reported disabilities exhibit attitudes and behaviours that are
      consistent with studies of students who are alienated from their school
      communities. Community-based health promotion interventions are required to
      address these issues in order to prevent the onset of secondary disease processes
      or additional disability.

PMID- 10896096
TI  - Factors associated with patients' participation in rehabilitation services: a
      comparative injury analysis 12 months post-discharge.
AB  - PURPOSE: To determine key characteristics or factors associated with
      rehabilitation participation during the first year following discharge for
      persons with either traumatic brain injury (TBI), spinal cord injury (SCI), intra
      articular fracture (IAF), or burn injury (BURNS). METHOD: Medical records and
      longitudinal survey [telephone questionnaire] data were collected for persons in
      the four injury groups and analyzed using hierarchical logistic regression
      procedures for each domain of factors. RESULTS: The only significant predictors
      with odds ratios greater than one were those for vocational rehabilitation
      participation. TBI patients lacking private insurance were 2.6 times more likely
      to participate in vocational rehabilitation; older SCI and TBI patients are about
      twice as likely to participate in vocational rehabilitation; and finally those
      with IAF or BURNS who are married at 12 months post discharge are 11.5 and 4.4
      times respectively more likely to participate in vocational rehabilitation.
      CONCLUSION: Those lacking valuable socio-economic resources, such as private
      insurance (for TBI) and social support systems provided by marriage (for BURNS
      and IAF patients) are much more likely to be referred to vocational
      rehabilitation. This is true for older SCI and TBI patients as well. Lacking such
      resources, patients may be viewed by referral agents as less likely to benefit
      from in or outpatient rehabilitation.

PMID- 10896097
TI  - Polytomous Rasch analysis as a tool for revision of the severity of disability
      code of the ICIDH.
AB  - PURPOSE: To develop a preliminary proposal for the revision of the severity code
      of the ICIDH-D 1980. METHOD: Quantitative analysis (polytomous Rasch analysis) of
      linked existing data sources including items about walking and dressing
      disability. RESULTS: The Rasch analysis provided estimates of threshold
      parameters for walking and dressing item categories. Factor analysis showed that
      more than one dimension was present, but that the first factor could definitely
      be interpreted as 'disability'. The reliability of the solutions was satisfactory
      (0.88 for walking and 0.91 for dressing). CONCLUSION: Based on the results,
      tentatively a new severity code is proposed with more distinct categories of
      'difficulty' than the existing code, and the use of technical aids and personal
      assistance in the higher ranks. The Rasch method could be a useful tool for
      calibrating and measuring disability, as well as for converting existing
      disability data into a new uniform severity of disability code.

PMID- 10896098
TI  - Sensitivity of a clinical scale of balance and gait in frail nursing home
      residents.
AB  - PURPOSE: The purpose of this paper was to describe this application, and to
      assess the sensitivity of the application when evaluating clinical interventions
      for improving balance and gait. METHODS: The records of fifteen consecutive
      patients referred to physical therapy for mobility problems or recent falls were
      reviewed for this study. The subjects were evaluated upon initial referral to
      physical therapy and after 30 days of treatment. Treatment was developed around
      the problems noted on initial evaluation and applied 5 days/week for 20 sessions.
      RESULTS: A Wilcoxon signed-rank comparison of the initial and 30 day re
      evaluation of the balance and the gait assessment indicated that significant
      improvement had occurred in the balance scores (Z = -3.20, p = 0.001) and the
      gait scores (Z = -2.82, p = 0.005) in this group. CONCLUSION: These assessments
      are sensitive to clinical improvements in mobility among frail elders.

PMID- 10896099
TI  - The role of quality management in the European platform for vocational
      rehabilitation.
AB  - PURPOSE: This paper explores the importance of applying the principles of quality
      management to vocational rehabilitation. METHOD/RESULTS: The role of the European
      Platform for Vocational Rehabilitation is outlined and a case made for
      incorporating quality into rehabilitation practice. The goal of this forum is to
      establish European co-operation in order to improve rehabilitation and vocational
      training and guidance for individuals with disabilities and social disadvantages.
      The work of this organization is set within the context of quality management.
      CONCLUSIONS: In exploring the role of the 'platform' it is suggested that there
      are benefits for rehabilitation professionals and individuals with disabilities
      in the European states working together to explore good practice.

PMID- 10896100
TI  - Trans-tibial amputee gait adaptations as a result of prosthetic inertial
      manipulation.
AB  - PURPOSE: To establish through gait analysis how changing the mass at the distal
      end of an in-house, custom-made trans-tibial dynamic elastic response prosthetic
      limb altered selected gait variables. Including; walking velocity, cadence,
      single support and hip power for a single amputee. METHOD: A before-after single
      subject research design was used with two interventions. A 3-dimensional gait
      analysis was conducted to analyse the effect on selected gait variables. The mass
      and moment of inertia of the prosthesis were altered by inserting wedges of
      different materials. RESULTS: Altering the mass had little effect on the cadence,
      single support or the velocity. Both the affected and intact limb hip pull-off
      power at terminal stance was increased, although the effect was greater for the
      affected limb than for the intact limb. The affected limb hip power at initial
      contact did not alter in a manner directly related to the mass. CONCLUSIONS:
      Altering the mass had an inconsistent effect on the gait parameters tested. The
      subject volunteered that he preferred the prosthesis of the middle mass.

PMID- 10896101
TI  - The discovery of [1-(4-dimethylamino-benzyl)-piperidin-4-yl]-[4-(3,3
      dimethylbutyl)-phen yl]-(3-methyl-but-2-enyl)-amine, an N-type Ca+2 channel
      blocker with oral activity for analgesia.
AB  - Our drug discovery efforts for N-type calcium channel blockers in the 4
      piperidinylaniline series led to the discovery of an orally active analgesic
      agent 26.1-[4-Dimethylamino-benzyl)-piperidin-4-yl]-[4-(3,3-dimethyl-but yl)
      phenyl]-(3-methyl-but-2-enyl)amine (26) showed high affinity to functionally
      block N-type calcium channels (IC50=0.7 microM in the IMR32 assay) and exhibited
      high efficacy in the anti-writhing analgesia test with mice (ED50=12 mg/kg by po
      and 4 mg/kg by iv). In this report, the rationale for the design, synthesis,
      biological evaluation, and pharmacokinetics of this series of blockers is
      described.

PMID- 10896102
TI  - Corticotropin releasing hormone: therapeutic implications and medicinal chemistry
      developments.
AB  - Corticotropin releasing hormone (CRH, sometimes known as CRF) is an endogenous 41
      amino acid peptide that has been implicated in the onset of pregnancy, the 'fight
      or flight' response, in addition to a large number of physiological disorders.
      Recently, medicinal chemists have developed a number of potent and selective
      compounds that show promise in a vast array of therapeutic uses. Herein we review
      the current status of research.

PMID- 10896103
TI  - Lincomycin and clindamycin conformations. A fragment shared by macrolides,
      ketolides and lincosamides determined from TRNOE ribosome-bound conformations.
AB  - Two important lincosamide antibiotics, lincomycin and clindamycin were studied in
      the complex state with the bacterial ribosome after a conformational analysis by
      1H and 13C NMR spectroscopy and molecular modelling of the unbound molecules.
      Lincosamide-ribosome interactions were investigated using two-dimensional
      transferred nuclear Overhauser effect spectroscopy (TRNOESY), resulting in a
      bound structure compatible with the experimental NMR data. The results compared
      with the conformational analysis of the substrates in solution indicate that
      specific conformations are preferred in the bound state. Clindamycin, the more
      bioactive antibiotic studied, displayed a stronger NMR response than lincomycin
      showing that in lincosamide-ribosome interactions, a low affinity binding level
      is associated to the tight binding one and is related to biological activity.
      This study shows that conformation plays an essential role for the low affinity
      binding site. Superimposition of lincosamide, macrolide and ketolide bound
      structures exhibited conformational similarities in a particular fragment which
      is in agreement with a hypothesis of partial overlapping lincosamide and
      macrolide binding sites.

PMID- 10896104
TI  - Novel imidazolyl and triazolyl substituted biphenyl compounds: synthesis and
      evaluation as nonsteroidal inhibitors of human 17alpha-hydroxylase-C17, 20-lyase
      (P450 17).
AB  - The synthesis of a new series of P450 17 inhibitors is described. The imidazol-1
      yl compounds 5 showed strong inhibition of P450 17 rat and especially human
      enzyme, the most active compounds being 5ax, 5ay and 5bx with IC50 values of
      0.17, 0.24 and 0.25 microM, respectively (ketoconazole: 0.74 microM). The 1,2,4
      triazol-1-yl compounds 6 were less active, while the 1,2,4-triazol-4-yl compounds
      7 were inactive. The title compounds showed little inhibition of P450 arom. The
      most active P450 17 inhibitors 5ax and 5ay markedly decreased the testosterone
      plasma concentration of SD rats 2 h after application of 0.019 mmol/kg. After 6
      h, 5ay still exhibited a strong effect.

PMID- 10896105
TI  - New anti-HIV derivatives: synthesis and antiviral evaluation.
AB  - A small focused library of 18 compounds incorporating the motif 1,3-(N,N'
      dibenzyl)diamino-2-propanol has been synthesized, using adapted synthetic
      methodologies. These series of compounds were evaluated for their in vitro anti
      HIV activity on infected MT4 cells (syncytium formation observation). Some of the
      new synthesized compounds show potent anti-HIV activities. EC50 values for
      compounds (31, 40, 34, 37 and 46) range from 0.1 to 1 microM. In order to
      determine at which level these new derivatives interfere with the HIV replicative
      cycle, inhibition assays on recombinant HIV protease and HIV integrase have been
      performed. None of the compounds were found active on these two enzymatic
      targets. Experiments are in progress in order to identify their biological target
      within the HIV replicative cycle.

PMID- 10896106
TI  - Tyrosine analogues as alternative substrates for protein tyrosine kinase Csk:
      insights into substrate selectivity and catalytic mechanism.
AB  - Protein tyrosine kinases are critical enzymes in cell signal transduction but
      relatively little is known about the molecular recognition of the tyrosine
      substrate by these enzymes. Details of tyrosine substrate specificity within the
      context of a short peptide were investigated for protein tyrosine kinase Csk. It
      was found that aryl ring functional group substitutions the size of methyl group
      or smaller were generally well tolerated by the protein tyrosine kinase Csk
      whereas larger groups caused a decline in substrate efficiency. Extension of the
      phenol from the peptide backbone by a single methylene was acceptable for
      phosphorylation whereas removal of a methylene nearly abolished reactivity. Only
      the L-tyrosine derivative was processed. A negative charge ortho to the phenol
      hydroxyl was incompatible with substrate reactivity, consistent with previous pH
      rate profiles which indicated the importance of the neutral phenol. Overall,
      these studies confirmed the interpretation of a previous linear free energy
      relationship analysis which suggested that the enzyme followed a dissociative
      transition state mechanism.

PMID- 10896107
TI  - Taxus canadensis abundant taxane: conversion to paclitaxel and rearrangements.
AB  - An efficient conversion of Taxus canadensis abundant taxane, 9-dihydro-13
      acetylbaccatin III to baccatin III is described. Since the synthesis of
      paclitaxel from baccatin III has been reported, this work can be used for
      additional supply of this powerful anticancer drug. In addition, new taxanes
      derived from skeletal rearrangements originating from oxidation reduction
      reactions of the Canadian yew major taxane, are reported.

PMID- 10896108
TI  - Aziridinyl peptides as inhibitors of cysteine proteases: effect of a free
      carboxylic acid function on inhibition.
AB  - Peptides containing aziridine-2,3-dicarboxylate (Azi) as electrophilic building
      block are evaluated as inhibitors of the cysteine proteases papain, cathepsin B,
      cathepsin L and clostripain. The influence of a free carboxylic acid as
      functional group at different positions of the inhibitor molecule on inhibition
      is analyzed. Structure-activity relationships and binding mode hypotheses are
      discussed. In contrast to the bacterial enzyme clostripain, the papain like
      mammalian proteases (cathepsins) are irreversibly inactivated by aziridinyl
      peptides. N-Unsubstituted aziridines are much more potent inhibitors of papain
      and cathepsins if they contain the free carboxylic acid attached to the aziridine
      ring (HOAzi-Leu-ProOBzl). Two free carboxylic acid functions at the aziridine
      ring are necessary for good inhibition of these enzymes by N-acylated aziridinyl
      peptides (BOC-Phe-Azi(OH)2). Chimeric bispeptidyl derivatives are selective CB
      inhibitors if the free acid is located at the C-terminus of the peptide (BOC-Phe
      (EtO)Azi-Leu-ProOH). Clostripain is only inhibited by aziridinyl peptide esters.

PMID- 10896110
TI  - Synthesis, incorporation efficiency, and stability of disulfide bridged
      functional groups at RNA 5'-ends.
AB  - Modified guanosine monophosphates have been employed to introduce various
      functional groups onto RNA 5'-ends. Applications of modified RNA 5'-ends include
      the generation of functionalized RNA libraries for in vitro selection of
      catalytic RNAs, the attachment of photoaffinity-tags for mapping RNA-protein
      interactions or active sites in catalytic RNAs, or the nonradioactive labeling of
      RNA molecules with fluorescent groups. While in these and in similar applications
      a stable linkage is desired, in selection experiments for generating novel
      catalytic RNAs it is often advantageous that a functional group is introduced
      reversibly. Here we give a quantitative comparison of the different strategies
      that can be applied to reversibly attach functional groups via disulfide bonds to
      RNA 5'-ends. We report the preparation of functional groups with disulfide
      linkages, their incorporation efficiency into an RNA library, and their stability
      under various conditions.

PMID- 10896109
TI  - Acyclic amides as estrogen receptor ligands: synthesis, binding, activity and
      receptor interaction.
AB  - We have prepared a series of bisphenolic amides that mimic bibenzyl and
      homobibenzyl motifs commonly found as substructures in ligands for the estrogen
      receptor (ER). Representative members were prepared from three classes: N-phenyl
      benzamides, N-phenyl acetamides, and N-benzyl benzamides; in some cases the
      corresponding thiocarboxamides and sulfonamides were also prepared. Of these
      three classes, the N-phenyl benzamides had the highest affinity for ER, the N
      phenyl acetamides had lower, and the N-benzyl benzamides were prone to
      fragmentation via a quinone methide intermediate. In the N-phenyl benzamide
      series, the highest affinity analogues had bulky N-substituents; a CF3 group, in
      particular, conferred high affinity. The thiocarboxamides bound better than the
      corresponding carboxamides and these bound better than the corresponding
      sulfonamides. Binding affinity comparisons suggest that the p-hydroxy group on
      the benzoate ring, which contributes most to the binding, is playing the role of
      the phenolic hydroxyl of estradiol. Computational studies and NMR and X-ray
      crystallographic analysis indicate that the two anilide systems studied have a
      strong preference for the s-cis or exo amide conformation, which places the two
      aromatic rings in a syn orientation. We used this structural template, together
      with the X-ray structure of the ER ligand binding domain, to elaborate an
      additional hydrogen bonding site on a benzamide system that elevated receptor
      binding further. When assayed on the individual ER subtypes, ERalpha and ERbeta,
      these compounds show modest binding affinity preference for ERalpha. In a
      reporter gene transfection assay of transcriptional activity, the amides
      generally have full to nearly full agonist character on ERalpha, but have
      moderate to full antagonist character on ERbeta. One high affinity carboxamide is
      500-fold more potent as an agonist on ERalpha than on ERbeta. This work
      illustrates that ER ligands having simple amide core structures can be readily
      prepared, but that high affinity binding requires an appropriate distribution of
      bulk, polarity, and functionality. The strong conformational preference of the
      core anilide function in all of these ligands defines a rather rigid geometry for
      further structural and functional expansion of these series.

PMID- 10896111
TI  - Observations on the covalent cross-linking of the binding domain (BD) of the high
      mobility group I/Y (HMG I/Y) proteins to DNA by FR66979.
AB  - FR66979, a drug closely related to the mitomycin C class of antitumor
      antibiotics, is shown to covalently cross-link DNA to the DNA-binding domain of
      the High Mobility Group I/Y (HMG I/Y) DNA-binding proteins in the minor groove.

PMID- 10896112
TI  - Multicomponent synthesis of novel amino acid-nucleobase chimeras: a versatile
      approach to PNA-monomers.
AB  - This paper describes a multicomponent approach to novel totally protected
      precursors of PNA-monomers via Ugi 4CC. The obtained bisamides are converted into
      several partially protected PNA-monomers or derivatives thereof using three
      different procedures. Methods for hydrolysis are shown to be dependent on the
      nature of the isocyano component required for Ugi 4CC. Several novel monomers
      suitable for oligomer synthesis are prepared demonstrating the high versatility
      of the reaction sequence.

PMID- 10896113
TI  - Antimalarial sulfide, sulfone, and sulfonamide trioxanes.
AB  - A series of trioxanes featuring sulfide, sulfone, and sulfonamide substituents in
      diverse positions has been prepared. Structure-activity relationship (SAR)
      generalizations highlight two major factors controlling the antimalarial potency
      of these new chemical entities: (1) the proximity of the sulfur-containing
      substituent to the crucial peroxide bond and (2) the oxidation state of the
      sulfur-containing substituent. Generally, sulfones are more antimalarially potent
      than the corresponding sulfides.

PMID- 10896114
TI  - 2"-Substituted 5-phenylterbenzimidazoles as topoisomerase I poisons.
AB  - 5-Phenylterbenzimidazole (1) is active as a topoisomerase I poison (topo I) and
      is cytotoxic to human tumor cells. No cross-resistance was observed for 1 when it
      was evaluated against the camptothecin-resistant cell line, CPT-K5. Derivatives
      of 1 substituted at the 2"-position, however, did exhibit cross-resistance to
      this cell line. The basis for the resistance of this cell line towards CPT is
      that it possesses a mutant form of topo I. These results suggest that
      substituents at the 2"-position may be in proximity to the wild-type enzyme.
      Therefore, we hypothesized that terbenzimidazoles with 2"-substituents could be
      capable of interacting with the enzyme and thereby influence activity within this
      class of topo I poisons. 5-Phenylterbenzimidazoles with a hydroxy, hydroxymethyl,
      mercapto, amino, N-benzoylaminomethyl, chloro, and trifluoromethyl group at the
      2"-position were synthesized. In addition, several 2"-ethyl-5
      phenylterbenzimidazoles were prepared containing either a methoxy, hydroxy,
      amino, or N-acetylamino group at the 2-position of the ethyl side-chain. These 2"
      substituted 5-phenylterbenzimidazoles were evaluated as topo I poisons and for
      cytotoxic activity. The presence of a strong electron-withdrawing group at the 2"
      position, such as a chloro or trifluoromethyl group, did enhance both topo I
      poisoning activity and cytotoxicity. Studies on the relative DNA binding affinity
      of 1 to its 2"-amino and 2"-trifluoromethyl derivatives did exhibit a correlation
      with their relative differences in biological activity.

PMID- 10896116
TI  - 6-Substituted 2,2-bis(fluoromethyl)-benzopyran-4-carboxamide K+ channel openers.
AB  - In the course of our study to find an ideal antihypertensive potassium channel
      opener (KCO), N-(2-cyanoethyl)-2,2-bis(fluoromethyl)-6-pentafluoroethyl-2H-1-ben
      zopyran-4-carboxamide (13f, KC-515) showed a highly potent, slow and long-lasting
      antihypertensive effect with reduced reflex tachycardia, together with the
      beneficial effects of KCO such as improvement in lipid metabolism. These profiles
      identify KC-515 as a potential candidate. In conscious spontaneously hypertensive
      rats (SHR), the onset of the hypotensive effect of KC-515 (13f) was gradual and
      the maximum response was attained at around 6 h after dosing. The duration of
      action was over 18 h for 0.1 mg/kg. When administered to Zucker rats for 2 weeks
      with 0.03-0.3 mg/kg po range in the antihypertensive doses in hypertensive rat
      models, KC-515 (13f) significantly and dose-dependently reduced serum
      triglycerides to less than 70% of control without affecting total cholesterol.

PMID- 10896115
TI  - 2,3-Dihydro-dithiin and -dithiepine-1,1,4,4-tetroxides: small molecule non
      peptide antagonists of the human galanin hGAL-1 receptor.
AB  - The neuropeptide galanin modulates several physiological functions such as
      cognition, learning, feeding behavior, and depression, probably via the galanin 1
      receptor (GAL-R1). Using an HTS assay based on 125I-human galanin binding to the
      human galanin-1 receptor (hGAL-R1), we discovered a series of 1,4-dithiin and
      dithiipine-1,1,4,4-tetroxides that exhibited binding affinity IC50's to hGAL-R1
      ranging from 190 to 2700 nM. Two of the dithiepin analogues, 7 and 23, behaved
      pharmacologically as hGAL-R1 antagonists in secondary assays involving adenylate
      cyclase activity and GTP binding to G-proteins. Analogues 7 and 23 were also
      active in functional assays involving galanin, reversing the inhibitory effect of
      galanin on acetylcholine (ACh) release in rat brain hippocampal slices and
      electrically-stimulated guinea pig ileum twitch.

PMID- 10896117
TI  - Synthesis of acyclic 6,7-dihaloquinolone nucleoside analogues as potential
      antibacterial and antiviral agents.
AB  - Reaction of the quinolone carboxylic acids 1 and 2 with (2-acetoxyethoxy)methyl
      chloride 3 in the presence of n-Bu4NI afforded the N-alkylated products 4 and 6,
      which could be deblocked to the free nucleoside analogues 5 and 7, respectively.
      The alkylated quinolone carboxylic acids 9 and 10 were obtained by condensation
      of I and 2 with 1,4-dichlorobut-2-ene 8 in the presence of NaH. Hydrolysis of 9
      gave the alcohol 11. Similar treatment of 1 with 8 in the presence of K2CO3 at
      relatively high temperature furnished 12. Prolonged heating of the ester 13 with
      8 in NaH/DMF afforded the conjugated-diene 15. Treatment of 1 and 2 with dimethyl
      acetylenedicarboxylate 16 furnished the pyrano[4,3-b]quinolones 17 and 18,
      respectively. Antibacterial and antiviral evaluations of the new products are
      reported.

PMID- 10896118
TI  - Pyrrolo-quinoline derivatives as potential antineoplastic drugs.
AB  - Some novel pyrrolo-quinoline derivatives have been synthesized as potential
      antineoplastic agents. They contain an angular aromatic tricyclic or tetracyclic
      system, to which the methanesulfon-anisidide side chain typical of amsacrine as
      such, or lacking the m-methoxy substituent, is connected. A methyl group can be
      present at position 7 of the pyrrolo-quinoline ring. The novel compounds exhibit
      interesting cell growth inhibitory properties when tested against the NCI panel
      of cell lines, in particular those obtained from solid tumors like CNS-, melanoma
      and prostate-derived cells. The mechanism of cytotoxic action does not seem to
      be related to topoisomerase II poisoning ability. Most active proved to be
      compound 4a, which lacks both methyl and methoxy substituents, followed by 5a,
      having the methoxy group only. Biological activity is less pronounced in the
      tetracyclic family of derivatives 6 and 7.

PMID- 10896119
TI  - Antimycobacterial pyrroles: synthesis, anti-Mycobacterium tuberculosis activity
      and QSAR studies.
AB  - A number of known antifungal pyrrole derivatives and some newly synthesized
      compounds (5-33) were tested in vitro against Mycobacterium tuberculosis CIP
      103471. The majority of tested compounds were efficient antimycobacterial agents
      showing MIC values ranging from 0.5 to 32 microg/mL. A 3-D-QSAR study has been
      performed on these pyrrole derivatives to correlate their chemical structures
      with their observed inhibiting activity against M. tuberculosis. Due to the
      absence of information on a putative receptor responsible for this activity,
      classical quantitative structure-activity relationships (QSAR) and comparative
      molecular field analysis (CoMFA) have been applied. A model able to well
      correlate the antimycobacterial activity with the chemical structures of pyrrole
      derivatives 5-33 has been developed which is potentially helpful in the design of
      novel and more potent antituberculosis agents. The combination of CoMFA with
      classical QSAR descriptors led to a better hybrid 3-D-QSAR model, that
      successfully explains the structure-activity relationships (r2 = 0.86) of the
      training set. A comparison between the QSAR, CoMFA and mixed QSAR-CoMFA models is
      also presented. The hybrid model is to be preferred, however, because of its
      lowest values of the average absolute error of prediction toward a limited
      external test set.

PMID- 10896120
TI  - Comparative molecular field analysis of colchicine inhibition and tubulin
      polymerization for combretastatins binding to the colchicine binding site on beta
      tubulin.
AB  - A molecular modeling study using Comparative Molecular Field Analysis (CoMFA) was
      undertaken to develop a predictive model for combretastatin binding to the
      colchicine binding site of tubulin. Furthermore, we examined the potential
      contribution of lipophilicity (log P) and molecular dipole moment and were unable
      to correlate these properties to the observed biological data. In this study we
      first confirmed that tubulin polymerization inhibition (IC50) correlated (R2 =
      0.92) with [3H]colchicine displacement. Although these data correlated quite
      well, we developed two independent models for each set of data to quantify
      structural features that may contribute to each biological property
      independently. To develop our predictive model we first examined a series of
      molecular alignments for the training set and ultimately found that overlaying
      the respective trimethoxyphenyl rings (A ring) of the analogues generated the
      best correlated model. The CoMFA yielded a cross-validated R2 = 0.41 (optimum
      number of components equal to 5) for the tubulin polymerization model and an R2 =
      0.38 (optimum number of components equal to 5) for [3H]colchicine inhibition.
      Final non-cross-validation generated models for tubulin polymerization (R2 of
      0.93) and colchicine inhibition (R2 of 0.91). These models were validated by
      predicting both biological properties for compounds not used in the training set.
      These models accurately predicted the IC50 for tubulin polymerization with an R2
      of 0.88 (n = 6) and those of [3H]colchicine displacement with an R2 of 0.80 (n =
      7). This study represents the first predictive model for the colchicine binding
      site over a wide range of combretastatin analogues.

PMID- 10896121
TI  - Bioisosteric replacement strategy for the synthesis of 1-azacyclic compounds with
      high affinity for the central nicotinic cholinergic receptors.
AB  - Bioisosteric replacement of the isoxazole heterocycle in (3-methyl-5
      isoxazolyl)methylene-azacyclic compounds with pyridine, oxadiazole, or an acyl
      group resulted in ligands with high to moderate affinity for the central
      nicotinic cholinergic receptors (IC50 = 2.0 to IC50 > 1000 nM) labeled by
      [3H]methylcarbamylcholine. Additionally, further support of an important distance
      parameter for high-affinity nicotinic compounds has been provided.

PMID- 10896122
TI  - Identification of new Cdc25 dual specificity phosphatase inhibitors in a targeted
      small molecule array.
AB  - Dual specificity protein phosphatases (DSPases) are key regulators of signal
      transduction, oncogenesis and the cell cycle. Few potent or specific inhibitors
      of DSPases, however, are readily available for these pharmacological targets. We
      have used a combinatorial/parallel synthetic approach to rigidify the variable
      core region and modify the side chains of 4-(benzyl-(2-[2,5-diphenyl-oxazole-4
      carbonyl)-amino]-ethyl)-carbamoyl)- 2-decanoylamino butyric acid (or SC
      alphaalphadelta9), which is the most active element in a previously described
      library of phosphatase inhibitors (Rice, R. L.; Rusnak, J. M.; Yokokawa, F.;
      Yokokawa, S.; Messner, D. J.; Boynton, A. L.; Wipf, P.; Lazo, J. S. Biochemistry
      1997, 36, 15965). Several analogues were identified as effective inhibitors of
      the protein tyrosine phosphatase (PTPase) PTP1B and the DSPases VHR and Cdc25B2.
      Two compounds, FY3-alphaalpha09 and FY21-alphaalpha09, were partial competitive
      inhibitors of Cdc25B2 with Ki values of 7.6+/-0.5 and 1.6+/-0.2 microM,
      respectively. FY21-alphaalpha09 possessed only moderate activity against PTP1B.
      Consistent with its in vitro anti-phosphatase activity, FY21-alphaalpha09
      inhibited growth in MDA-MB-231 and MCF-7 human breast cancer cell lines. FY21
      alphaalpha09 also inhibited the G2/M transition in tsFT210 cells, consistent with
      Cdc25B inhibition. Several architectural requirements for DSPase inhibition were
      revealed through modification of the side chain moieties or variable core region
      of the pharmacophore, which resulted in decreased compound potency. The structure
      of FY21-alphaalpha09 provides a useful platform from which additional potent and
      more highly selective phosphatase inhibitors might be generated.

PMID- 10896123
TI  - Bromal-derived tetrahydro-beta-carbolines as neurotoxic agents: chemistry,
      impairment of the dopamine metabolism, and inhibitory effects on mitochondrial
      respiration.
AB  - The mammalian alkaloids tryptoline (1) and eleagnine (2) as well as the highly
      halogenated (X = F, Cl, Br) tetrahydro-beta-carbolines (THbetaCs) 3-5,
      structurally similar to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP, 6), were found to have a common feature of inducing a
      severe impairment of the nigrostriatal dopamine metabolism and inhibiting complex
      I of the mitochondrial respiratory chain highly selectively. Within the series of
      compounds tested, 1-tribromomethyl-1,2,3,4-tetrahydro-beta-carboline ('TaBro',
      5), which was prepared in high yields from the biogenic amine tryptamine ('Ta',
      7) and the unnatural aldehyde bromal ('Bro', 8) by a Pictet-Spengler cyclization
      reaction, turned out to be the most potent toxin in vitro and in vivo. As
      demonstrated by voltammetric measurements on rats, for all the THbetaCs 1-5
      investigated, intranigral application of a single dose of 10 microg resulted in a
      significant reduction of the dopaminergic activity in the striatum, with the
      strongest effect being observed for TaBro (5). Using rat brain homogenates, again
      5 (IC50 = 200 microM) as well as its dehydrohalogenation product 11 (IC50 = 150
      microM) exhibited the most pronounced inhibitory potential on mitochondrial
      respiration. The halogen-free THbetaCs 1 and 2 as well as the MPTP metabolite 1
      methyl-4-phenylpyridinium ion (MPP+), by contrast, showed only a moderate
      inhibition at concentrations in the millimolar range (e.g. for MPP+: IC50 = 3.5
      mM). For an elucidation of the role of hydrophobic portion in the inhibitory
      action against complex I activity, several N-acyl derivatives (15-21) of 5 were
      synthesized and tested. An X-ray diffraction study on the 3-dimensional structure
      of trifluoroacetylated highly halogenated THbetaCs (12-14) revealed the
      tetrahydropyrido part to adopt a nearly planarized half-chair conformation.
      Because of the steric demand of the trihalogenmethyl moiety (CF3 < CCl3 < CBr3),
      the N-substituent is dramatically pushed out of that ring 'plane'.

PMID- 10896124
TI  - Synthesis of N-substituted piperidine-4-(benzylidene-4-carboxylic acids) and
      evaluation as inhibitors of steroid-5alpha-reductase type 1 and 2.
AB  - The synthesis of N-substituted piperidine-4-(benzylidene-4-carboxylic acids) is
      described [benzoyl (1), benzyl (2), adamantanoyl (3), cyclohexanoyl (4),
      cyclohexylacetyl (5), diphenylacetyl (6), dicyclohexylacetyl (7), 2
      propylpentanoyl (8), diphenylcarbamoyl (9), trimethylacetyl (10), 3,3
      dimethylacryloyl (11), dicyclohexylacetyl derivative of the benzyl compound
      (12)]. Compounds were tested for inhibitory activity toward 5alpha-reductase
      isozymes 1 and 2 in human and rat. The test compounds inhibited 5alpha-reductase,
      showing a broad range of inhibitory potencies. In rat, compounds 6 (IC50 = 3.44
      and 0.37 microM for type 1 and 2, respectively) and 9 (IC50=0.54 and 0.69 microM
      for type 1 and 2, respectively) displayed the best inhibition toward both
      isozymes. Compound 7 showed a strong inhibition toward type 2 human and rat
      enzyme (IC50 = 60 and 80 nM) but only a moderate activity versus type 1 enzyme
      (IC50 approximately 10 microM for rat and human enzyme). In vivo, selected
      compounds reduced prostate weights in castrated testosterone treated rats.

PMID- 10896125
TI  - Coumarinic derivatives as mechanism-based inhibitors of alpha-chymotrypsin and
      human leukocyte elastase.
AB  - Novel coumarinic derivatives were synthesized and tested for their inhibitory
      potency toward alpha-CT and HLE. Cycloalkyl esters and amides were found to be
      essentially inactive on both enzymes. On the opposite, aromatic esters strongly
      inactivated alpha-CT whereas HLE was less efficiently inhibited with
      dichlorophenyl ester derivatives (kinact/K(I) = 4000 M(-1) s(-1) for 36).
      Representative examples of amide, ester, thioester and ketone derivatives were
      prepared in order to evaluate the influence of the link between the coumarinic
      ring and the phenyl side chain. The irreversible inactivation of alpha-CT by 6
      chloromethyl derivatives should be due to alkylation of a histidine residue as
      suggested by the amino acid analysis of the modified chymotrypsin. Conversely the
      inhibition of HLE was transient. Intrinsic reactivity of coumarins has been
      calculated using a model of a nucleophilic reaction between the ligand and the
      couple methanol-water. From this calculation, it appears that differences in the
      inhibitory potency expressed by these molecules cannot only be explained by
      differences in the reactivity of the lactonic carbonyl group toward the
      nucleophilic attack.

PMID- 10896126
TI  - Substituted 1-phenyl-2-cyclopropylmethylamines with high affinity and selectivity
      for sigma sites.
AB  - A series of 1-phenyl-2-cyclopropylmethylamines structurally related to (+)- and (
      )-MPCB were synthesized and their binding affinities for sigma1, sigma2, opioid
      and dopamine (D2) receptors were evaluated. Substitution of the cis-N
      normetazocine with different aminic moieties provided compounds with high
      affinity and selectivity for sigma binding sites with respect to opioid and
      dopamine (D2) receptors. The observed increase in sigma2 affinity as compared to
      the parent (+)-MPCB, supports the idea that the particular stereochemistry of (+)
      cis-N-normetazocine affects sigma1 selectivity but does not affect sigma1
      affinity. The (+/-)-cis isomers of methyl 2-[(1-adamantylamino)methyl]-1
      phenylcyclopropane-1-carboxyl ate (18) displayed a higher affinity and
      selectivity for the sigma1 and sigma2 receptor subtypes compared to the (+/-)
      trans 19. Interestingly, the enantiomer (-)-cis 18 displayed a preference for
      sigma1 receptor subtype whereas the (+)-cis 18 did for sigma2. These results
      prompt us to synthesize compounds with modification of nitrogen and carboxyl
      groups. The compounds obtained showed high affinities and selectivity for sigma
      sites. Moreover, modifications of carboxyl groups provided compounds with the
      highest affinities in the series. In particular, compound 25 with reverse-type
      ester showed a Ki of 0.6 and 4.05 nM for sigma1 and sigma2 binding sites,
      respectively.

PMID- 10896127
TI  - Alkyl and alkoxycarbonyl derivatives of ginkgolide B: synthesis and biological
      evaluation of PAF inhibitory activity.
AB  - Alkyl and alkoxycarbonyl derivatives 6-24 of ginkgolide B, prepared in one step
      from ginkgolide B through alkylation and acylation and evaluated for their in
      vitro ability to inhibit the PAF-induced aggregation of rabbit platelets, show
      equivalent or superior activities to ginkgolide B.

PMID- 10896128
TI  - The significance of a coincidence between evolutionary landmarks found in mating
      affinity and a DNA sequence.

PMID- 10896129
TI  - FtsZ and organelle division in Protists.

PMID- 10896130
TI  - Dictyostelium, a model organism for microtubule-based transport.

PMID- 10896131
TI  - Investigations on gene copy number, introns and chromosomal arrangement of genes
      encoding the fucoxanthin chlorophyll a/c-binding proteins of the centric diatom
      Cyclotella cryptica.
AB  - The gene arrangement, existence of introns and the number of gene copies of genes
      (fcps) encoding fucoxanthin chlorophyll a/c-binding proteins (Fcps) of the
      centric diatom Cyclotella cryptica were investigated by polymerase chain reaction
      (PCR), Southern blotting and denaturing gradient gel electrophoresis (DGGE)
      experiments. PCR-mediated amplification of the fcp genes using chromosomal DNA as
      template demonstrated the absence of introns within the amplified regions.
      Clustering of genes could not be demonstrated in these experiments. Digestion of
      chromosomal DNA of Cy. cryptica followed by Southern blotting and hybridization
      with specific fcp probes revealed minimum and maximum values of 12 and 20,
      respectively, for the gene copies. In addition, the DGGE technique confirmed and
      strengthened the results obtained from Southern blotting experiments as
      amplification of gene fragments from genomic DNA with different sets of specific
      primers revealed values of 21 and 23, for the minimum and maximum gene copy
      number, respectively.

PMID- 10896132
TI  - Ultrastructure and 18S rDNA sequence analysis of Wobblia lunata gen. et sp. nov.,
      a new heterotrophic flagellate (Stramenopiles, Incertae sedis).
AB  - A new heterotrophic flagellate Wobblia lunata gen. et sp. nov. is described. This
      organism usually attaches to the substratum showing a wobbling motion, and
      sometimes glides on the substratum or swims freely in the medium. W. lunata has
      various features characteristic of the stramenopiles. These include a hairy
      flagellum with tripartite tubular hairs, a mitochondrion with tubular cristae,
      arrangement of flagellar apparatus components and a double helix in the flagellar
      transition zone. W. lunata shares a double helix with heterotrophic
      stramenopiles, including Developayella elegans, oomycetes, hyphochytrids,
      opalinids and proteromonads, and could be placed in the phylum Bigyra Cavalier
      Smith. However, from 18S rDNA tree analysis, these organisms form two distantly
      related clades in the stramenopiles, and Wobblia appears at the base of the
      stramenopiles. Evaluation of morphological features and comparison of 18S rDNA
      sequences indicate that W. lunata is a member of the stramenopiles, but it is
      distinct from any other stramenopiles so far described. Its phylogenetic position
      within the stramenopiles is uncertain and therefore W. lunata is described as a
      stramenopile incertae sedis.

PMID- 10896133
TI  - The Leishmania major RNA polymerase II largest subunit lacks a carboxy-terminus
      heptad repeat structure and its encoding gene is linked with the calreticulin
      gene.
AB  - The gene encoding the RNA polymerase II largest subunit (RPOIILS) has been
      isolated and sequenced from the kinetoplastid protozoan, Leishmania (Leishmania)
      major. The RPOIILS gene was shown to be present as a single copy and is composed
      of an uninterrupted open reading frame of 4.99 kb, specifying a protein 1663 aa
      in length with a predicted molecular mass of approximately 185 kDa. The carboxy
      terminus domain (CTD) of the RPOIILS from L. (L.) major, typical of the more
      evolutionary primitive protozoa, lacked a heptad repeat structure which is
      present in higher eukaryotes and some other protozoan phyla. Comparison of the
      predicted aa composition of the CTD from a diverse range of eukaryotic species
      revealed the abundance of Ser and Pro residues as the only discernible
      evolutionary conservative feature. A putative ATG start codon for an additional
      expressed sequence was located 1.1 kb downstream of the L. (L.) major RPOIILS
      gene stop codon. Nucleic acid database searches revealed the identity of this
      gene as that encoding the calcium binding protein calreticulin (CLT). The close
      proximity of the RPOIILS and CLT genes in L. (L.) major raises the possibility
      that these genes are transcribed as part of the same polycistronic unit.

PMID- 10896134
TI  - Estimating the growth potential of the soil protozoan community.
AB  - We have developed a method for determining the potential abundance of free-living
      protozoa in soil. The method permits enumeration of four major functional groups
      (flagellates, naked amoebae, testate amoebae, and ciliates) and it overcomes some
      limitations and problems of the usual 'direct' and 'most probable number'
      methods. Potential abundance is determined using light microscopy, at specific
      time intervals, after quantitative re-wetting of air-dried soil with rain water.
      No exogenous carbon substrates or mineral nutrients are employed, so the
      protozoan community that develops is a function of the resources and inhibitors
      present in the original field sample. The method was applied to 100 soil samples
      (25 plots x 4 seasons) from an upland grassland (Sourhope, Southern Scotland) in
      the UK. Median abundances for all four functional groups lie close to those
      derived from the literature on protozoa living in diverse soil types. Flagellates
      are the most abundant group in soil, followed by the naked amoebae, then the
      testate amoebae and ciliates. This order is inversely related to typical organism
      size in each group. Moreover, preliminary evidence indicates that each functional
      group contains roughly the same number of species. All of these observations
      would be consistent with soil having fractal structure across the size-scale
      perceived by protozoa. The method described will be useful for comparing the
      effects on the soil protozoan community of different soil treatments (e.g. liming
      and biocides).

PMID- 10896135
TI  - Karl G. Grell and the mid-20th century renaissance of protozoology in Germany.

PMID- 10896136
TI  - Structure determination of tubular crystals of membrane proteins. I. Indexing of
      diffraction patterns.
AB  - Indexing of diffraction patterns is the starting point of every crystallographic
      analysis. The diffraction patterns from helical particles consist of a series of
      layer-planes, the indexing of which involves the assignment of the start numbers
      of the helices that contribute to the layer-planes. The indexing could be
      challenging if the diameter of the helical particle is large and if the
      conventional indexing methods based on selection rule is used. Presented here is
      a tutorial on how to index them using (h, k; n) indexing method, which is
      particularly useful for tubular crystals of membrane proteins.

PMID- 10896137
TI  - Structure determination of tubular crystals of membrane proteins. II. Averaging
      of tubular crystals of different helical classes.
AB  - A set of programs has been developed for averaging the data from tubular crystals
      belonging to different helical classes. This was done either by (i) cutting out
      molecules constituting a unit cell from density maps, and aligning and averaging
      them in real space; (ii) transforming the densities in a unit cell to layer-line
      data according to a (possibly artificial) helical symmetry, aligning and
      averaging them in reciprocal space. These methods were applied to tubular
      crystals of Ca2+-ATPase. Either method worked well and substantially improved the
      data quality. Transforming the reconstructed images to the layer-line data has
      many advantages and is essential for fully exploiting the power of averaging.

PMID- 10896138
TI  - Structure determination of tubular crystals of membrane proteins. III. Solvent
      flattening.
AB  - Solvent flattening is considered to be a principal means for improving the data
      quality in X-ray crystallography. It could be equally effective for tubular
      crystals of membrane proteins imaged by electron microscopy because of the large
      empty space inside the tubes. However, tubular crystals are difficult objects for
      solvent flattening due to lack of electron diffraction amplitudes. Therefore,
      solvent flattening was used to align images more accurately and to improve the
      completeness of the data by reducing contributions of noise in the solvent (+
      lipid) region. The methods developed were tested with the tubular crystals of
      Ca2+-ATPase embedded in amorphous ice. The improvement of the data quality was
      remarkable when solvent flattening was applied to many individual images before
      averaging. In this way, noises contaminated in the protein region by contrast
      transfer function were removed effectively. Solvent flattening was far more
      powerful than simple averaging described in Part II of this series (K. Yonekura,
      C. Toyoshima, Ultramicroscopy 84 (2000) 15).

PMID- 10896139
TI  - Automated identification of symmetry in CBED patterns: a genetic approach
AB  - The genetic algorithm has been applied for automated identification of symmetry
      in CBED patterns. A normalized inner product between an original and its symmetry
      operated CBED patterns was found to be a good measure of similarity between them,
      and this inner product was used as the objective function in the genetic
      algorithm. A real floating number implementation of this genetic approach has
      been applied successfully in identifying rotation axes and mirror planes in
      experimental CBED patterns obtained from a single crystal of silicon. In
      particular a three-fold rotation axis reflecting the true three-dimensional
      symmetry of silicon is clearly distinguished from a six-fold rotation axis as
      expected from a two-dimensional crystal in the experimental <1 1 1> zone axis
      CBED pattern.

PMID- 10896140
TI  - Defocus-gradient corrected back-projection.
AB  - Three-dimensional reconstructions of icosahedral viruses from cryoelectron
      microscope images have reached resolutions where the microscope depth of field is
      a significant resolution-limiting factor. An analytical treatment presented here
      shows how the depth of field limitation can be understood as an envelope function
      which gradually attenuates the signal, starting well before the numerical depth
      of field is actually reached. A simple modification to the well-known back
      projection reconstruction algorithm is described, called the defocus-gradient
      corrected back-projection, which computationally corrects for the contrast
      transfer function along a defocus gradient. Computer simulations demonstrate how
      the algorithm effectively eliminates the depth of field limitation.

PMID- 10896141
TI  - Annular dark-field image simulation of the YBa2Cu3O(7-delta)/BaF2 interface
AB  - Scanning transmission electron microscope (STEM) images of the interface of a
      YBa2Cu3O(7-delta) (YBCO)/BaF2 thin film bilayer show a relatively wide
      (approximately 40 A) contrasting band at the interface when viewed edge-on.
      Simulation of annular dark-field (ADF) images of this interface reveal that a
      significant contribution to this wide band of contrast is due to strain from
      dislocations oriented perpendicular to the incident beam direction and this
      contrast cannot be explained using solely a Z-contrast interpretation of ADF
      images. We believe that these are the first such calculations which predict that
      the presence of a misfit dislocation network can contribute a significant amount
      of contrast to cross-section ADF images of an interface.

PMID- 10896142
TI  - Multiport-readout frame-transfer 5 megapixel CCD imaging system for TEM
      applications.
AB  - A multiport-readout, frame-transfer charge-coupled device (CCD) digital imaging
      system has been successfully developed and tested for intermediate-high-voltage
      electron microscopy (IVEM) applications up to 400 keV. The system employs a back
      thinned CCD with 2560 x 1960 pixels and a pixel size of 24 microm x 24 microm. In
      the current implementation, four of the eight on-chip readout ports are used in
      parallel each operating at a pixel rate of 1- or 2-MHz so that the entire CCD
      array can be read out in as short as 0.6 s. The frame-transfer readout functions
      as an electronic shutter which permits the rapid transfer of charges in the
      active pixels to four masked buffers where the charges are readout and digitized
      while the active area of the CCD is integrating the next frame. With a thin film
      based phosphor screen and a high-performance lens relay, the system has a
      conversion factor of 2.1 digital units per incident electron at 400 keV, and a
      modulation transfer function value of 14% at the Nyquist frequency.

PMID- 10896143
TI  - Mapping and fuzzy classification of macromolecular images using self-organizing
      neural networks.
AB  - In this work the effectiveness of the fuzzy kohonen clustering network (FKCN) in
      the unsupervised classification of electron microscopic images of biological
      macromolecules is studied. The algorithm combines Kohonen's self-organizing
      feature maps (SOFM) and Fuzzy c-means (FCM) in order to obtain a powerful
      clustering technique with the best properties inherited from both. Exploratory
      data analysis using SOFM is also presented as a step previous to final
      clustering. Two different data sets obtained from the G40P helicase from B.
      Subtilis bacteriophage SPP1 have been used for testing the proposed method, one
      composed of 2458 rotational power spectra of individual images and the other
      composed by 338 images from the same macromolecule. Results of FKCN are compared
      with self-organizing feature maps (SOFM) and manual classification. Experimental
      results prove that this new technique is suitable for working with large, high
      dimensional and noisy data sets and, thus, it is proposed to be used as a
      classification tool in electron microscopy.

PMID- 10896144
TI  - HREM of CoSi2/SiC heterophase interface: facts and artifacts in the interface
      distance profile measurements
AB  - When studying heterophase interfaces, one of the ultimate goals is to determine
      the local distortions and to extract a chemical profile. In this respect, HREM is
      a powerful tool. Nevertheless, the non-linearity of the image formation leads to
      artifacts both in the images and in the distance profiles extracted from the
      images. The present SiC/silicide interface study illustrates the
      misinterpretation, which might arise from measurements made on images recorded
      under limited experimental conditions.

PMID- 10896145
TI  - Thermal noise reduction of mechanical oscillators by actively controlled external
      dissipative forces
AB  - We show that the thermal fluctuations of very soft mechanical oscillators, such
      as the cantilever in an atomic force microscope (AFM), can be reduced without
      changing the stiffness of the spring or having to lower the environment
      temperature. We derive a theoretical relationship between the thermal
      fluctuations of an oscillator and an actively controlled external dissipative
      force. This relationship is verified by experiments with an AFM cantilever where
      the external active force is coupled through a magnetic field. With simple
      instrumentation, we have reduced the thermal noise amplitude of the cantilever by
      a factor of 3.4, achieving an apparent temperature of 25 K with the environment
      at 295 K. This active noise reduction approach can significantly improve the
      accuracy of static position or static force measurements in a number of practical
      applications.

PMID- 10896146
TI  - More cables to Abl.

PMID- 10896147
TI  - Timing isn't everything.

PMID- 10896148
TI  - An optimal preparation for studying optimization.

PMID- 10896149
TI  - Attending to contrast.

PMID- 10896150
TI  - The making of a synapse: target-derived signals and presynaptic differentiation.

PMID- 10896151
TI  - In hot pursuit of the elusive heat transducers.

PMID- 10896152
TI  - Pretraining and the function of hippocampal long-term potentiation.

PMID- 10896153
TI  - Neural coding.

PMID- 10896154
TI  - Mathematical modeling of gene networks.

PMID- 10896155
TI  - Optical imaging of calcium transients in neurons and pharyngeal muscle of C.
      elegans.
AB  - Electrophysiology and optical indicators have been used in vertebrate systems to
      investigate excitable cell firing and calcium transients, but both techniques
      have been difficult to apply in organisms with powerful reverse genetics. To
      overcome this limitation, we expressed cameleon proteins, genetically encoded
      calcium indicators, in the pharyngeal muscle of the nematode worm Caenorhabditis
      elegans. In intact transgenic animals expressing cameleons, fluorescence ratio
      changes accompanied muscular contraction, verifying detection of calcium
      transients. By comparing the magnitude and duration of calcium influx in wild
      type and mutant animals, we were able to determine the effects of calcium channel
      proteins on pharyngeal calcium transients. We also successfully used cameleons to
      detect electrically evoked calcium transients in individual C. elegans neurons.
      This technique therefore should have broad applications in analyzing the
      regulation of excitable cell activity in genetically tractable organisms.

PMID- 10896156
TI  - Gating of Ca2+-activated K+ channels controls fast inhibitory synaptic
      transmission at auditory outer hair cells.
AB  - Fast inhibitory synaptic transmission in the central nervous system is mediated
      by ionotropic GABA or glycine receptors. Auditory outer hair cells present a
      unique inhibitory synapse that uses a Ca2+-permeable excitatory acetylcholine
      receptor to activate a hyperpolarizing potassium current mediated by small
      conductance calcium-activated potassium (SK) channels. It is shown here that
      unitary inhibitory postsynaptic currents at this synapse are mediated by SK2
      channels and occur rapidly, with rise and decay time constants of approximately 6
      ms and approximately 30 ms, respectively. This time course is determined by the
      Ca2+ gating of SK channels rather than by the changes in intracellular Ca2+. The
      results demonstrate fast coupling between an excitatory ionotropic
      neurotransmitter receptor and an inhibitory ion channel and imply rapid,
      localized changes in subsynaptic calcium levels.

PMID- 10896157
TI  - GRASP-1: a neuronal RasGEF associated with the AMPA receptor/GRIP complex.
AB  - The PDZ domain-containing proteins, such as PSD-95 and GRIP, have been suggested
      to be involved in the targeting of glutamate receptors, a process that plays a
      critical role in the efficiency of synaptic transmission and plasticity. To
      address the molecular mechanisms underlying AMPA receptor synaptic localization,
      we have identified several GRIP-associated proteins (GRASPs) that bind to
      distinct PDZ domains within GRIP. GRASP-1 is a neuronal rasGEF associated with
      GRIP and AMPA receptors in vivo. Overexpression of GRASP-1 in cultured neurons
      specifically reduced the synaptic targeting of AMPA receptors. In addition, the
      subcellular distribution of both AMPA receptors and GRASP-1 was rapidly regulated
      by the activation of NMDA receptors. These results suggest that GRASP-1 may
      regulate neuronal ras signaling and contribute to the regulation of AMPA receptor
      distribution by NMDA receptor activity.

PMID- 10896158
TI  - C. elegans locomotory rate is modulated by the environment through a dopaminergic
      pathway and by experience through a serotonergic pathway.
AB  - Caenorhabditis elegans modulates its locomotory rate in response to its food,
      bacteria, in two ways. First, well-fed wild-type animals move more slowly in the
      presence of bacteria than in the absence of bacteria. This basal slowing response
      is mediated by a dopamine-containing neural circuit that senses a mechanical
      attribute of bacteria and may be an adaptive mechanism that increases the amount
      of time animals spend in the presence of food. Second, food-deprived wild-type
      animals, when transferred to bacteria, display a dramatically enhanced slowing
      response that ensures that the animals do not leave their newly encountered
      source of food. This experience-dependent response is mediated by serotonergic
      neurotransmission and is potentiated by fluoxetine (Prozac). The basal and
      enhanced slowing responses are distinct and separable neuromodulatory components
      of a genetically tractable paradigm of behavioral plasticity.

PMID- 10896159
TI  - Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase
      upregulation, and neurite outgrowth.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a small serine/threonine kinase that plays a
      pivotal role during development of the CNS. Cables, a novel protein, interacts
      with Cdk5 in brain lysates. Cables also binds to and is a substrate of the c-Abl
      tyrosine kinase. Active c-Abl kinase leads to Cdk5 tyrosine phosphorylation, and
      this phosphorylation is enhanced by Cables. Phosphorylation of Cdk5 by c-Abl
      occurs on tyrosine 15 (Y15), which is stimulatory for p35/Cdk5 kinase activity.
      Expression of antisense Cables in primary cortical neurons inhibited neurite
      outgrowth. Furthermore, expression of active Abl resulted in lengthening of
      neurites. The data provide evidence for a Cables-mediated interplay between the
      Cdk5 and c-Abl signaling pathways in the developing nervous system.

PMID- 10896160
TI  - TRPgamma, a drosophila TRP-related subunit, forms a regulated cation channel with
      TRPL.
AB  - TRP and TRPL are two light-sensitive cation channel subunits required for the
      Drosophila photoresponse; however, our understanding of the identities, subunit
      composition, and function of the light-responsive channels is incomplete. To
      explain the residual photoresponse that remains in the trp mutant, a third TRP
      related subunit has previously been proposed to function with TRPL. Here, we
      identify such a subunit, TRPgamma. We show that TRPgamma is highly enriched in
      photoreceptor cells and preferentially heteromultimerizes with TRPL in vitro and
      in vivo. The N-terminal domain of TRPgamma dominantly suppressed the TRPL
      dependent photoresponse, indicating that TRPgamma-TRPL heteromultimers contribute
      to the photoresponse. While TRPL and TRPgamma homomultimers are constitutively
      active, we demonstrate that TRPL-TRPgamma heteromultimers form a regulated
      phospholipase C- (PLC-) stimulated channel.

PMID- 10896161
TI  - Activity coregulates quantal AMPA and NMDA currents at neocortical synapses.
AB  - AMPA and NMDA receptors are coexpressed at many central synapses, but the factors
      that control the ratio of these two receptors are not well understood. We
      recorded mixed miniature or evoked synaptic currents arising from coactivation of
      AMPA and NMDA receptors and found that long-lasting changes in activity scaled
      both currents up and down proportionally through changes in the number of
      postsynaptic receptors. The ratio of NMDA to AMPA current was similar at
      different synapses onto the same neuron, and this relationship was preserved
      following activity-dependent synaptic scaling. These data show that AMPA and NMDA
      receptors are tightly coregulated by activity at synapses at which they are both
      expressed and suggest that a mechanism exists to actively maintain a constant
      receptor ratio across a neuron's synapses.

PMID- 10896162
TI  - Selective depression of low-release probability excitatory synapses by sodium
      channel blockers.
AB  - Sodium channels (NaChs) play a central role in action potential generation and
      are uniquely poised to influence the efficacy of transmitter release. We
      evaluated the effect of partial NaCh blockade on two aspects of synaptic efficacy
      First, we evaluated whether NaCh blockade accounts for the ability of certain
      drugs to selectively depress glutamate release. Second, we evaluated the
      contribution of NaChs to intraneuronal variability in glutamate release
      probability (p(r)). The antiglutamate drug riluzole nearly completely depresses
      glutamate excitatory postsynaptic currents (EPSCs) at concentrations that barely
      affect GABAergic inhibitory postsynaptic currents (IPSCs). NaCh inhibition
      explains the selective depression. Unlike other presynaptic depressants, partial
      NaCh blockade increases paired-pulse EPSC depression. This result is explained by
      selective depression of low-p(r) synapses. We conclude that local variations in
      the action potential contribute to p(r) variability among excitatory synapses.

PMID- 10896163
TI  - Inhibitory transmission mediated by asynchronous transmitter release.
AB  - At fast CNS synapses, the role of asynchronous release following initial
      synchronous release is poorly understood. We examined the contribution of
      asynchronous release to GABAergic transmission in the cochlear nucleus across a
      40-fold range of electrical stimulus frequencies. Whereas quantal release was
      highly synchronized at low frequencies, it was largely continuous and
      desynchronized at high frequencies. Despite the change in release mode, intense
      and steady inhibitory transmission was virtually maintained. Experimental
      analyses and modeling studies indicated that this "desynchronization" process was
      dependent on presynaptic Ca2+ accumulation, facilitation of vesicle release, and
      short-term depletion of available vesicles. Asynchronous release at high
      frequencies may help generate a smooth inhibitory "tone" by minimizing the
      consequences of random timing of presynaptic action potentials.

PMID- 10896164
TI  - Adaptive rescaling maximizes information transmission.
AB  - Adaptation is a widespread phenomenon in nervous systems, providing flexibility
      to function under varying external conditions. Here, we relate an adaptive
      property of a sensory system directly to its function as a carrier of information
      about input signals. We show that the input/output relation of a sensory system
      in a dynamic environment changes with the statistical properties of the
      environment. Specifically, when the dynamic range of inputs changes, the
      input/output relation rescales so as to match the dynamic range of responses to
      that of the inputs. We give direct evidence that the scaling of the input/output
      relation is set to maximize information transmission for each distribution of
      signals. This adaptive behavior should be particularly useful in dealing with the
      intermittent statistics of natural signals.

PMID- 10896165
TI  - Attention increases sensitivity of V4 neurons.
AB  - When attention is directed to a location in the visual field, sensitivity to
      stimuli at that location is increased. At the neuronal level, this could arise
      either through a multiplicative increase in firing rate or through an increase in
      the effective strength of the stimulus. To test conflicting predictions of these
      alternative models, we recorded responses of V4 neurons to stimuli across a range
      of luminance contrasts and measured the change in response when monkeys attended
      to them in order to discriminate a target stimulus from nontargets. Attention
      caused greater increases in response at low contrast than at high contrast,
      consistent with an increase in effective stimulus strength. On average, attention
      increased the effective contrast of the attended stimulus by a factor of 1.51, an
      increase of 51% of its physical contrast.

PMID- 10896166
TI  - Neural correlates of contrast detection at threshold.
AB  - Human psychophysical studies have demonstrated that, for stimuli near the
      threshold of visibility, detection of motion in one direction is unaffected by
      the superimposition of motion in the opposite direction. To investigate the
      neural basis for this perceptual phenomenon, we recorded from directionally
      selective neurons in macaque visual area MT (middle temporal visual area).
      Contrast thresholds obtained for single gratings moving in a neuron's preferred
      direction were compared with those obtained for motion presented simultaneously
      in the neuron's preferred and antipreferred directions. A simple model based on
      probability summation between neurons tuned to opposite directions could
      sufficiently account for contrast thresholds revealed psychophysically,
      suggesting that area MT is likely to provide the neural basis for contrast
      detection of stimuli modulated in time.

PMID- 10896167
TI  - Segregation of object and background motion in visual area MT: effects of
      microstimulation on eye movements.
AB  - To track a moving object, its motion must first be distinguished from that of the
      background. The center-surround properties of neurons in the middle temporal
      visual area (MT) may be important for signaling the relative motion between
      object and background. To test this, we microstimulated within MT and measured
      the effects on monkeys' eye movements to moving targets. We found that
      stimulation at "local motion" sites, where receptive fields possessed
      antagonistic surrounds, shifted pursuit in the preferred direction of the
      neurons, whereas stimulation at "wide-field motion" sites shifted pursuit in the
      opposite, or null, direction. We propose that activating wide-field sites
      simulated background motion, thus inducing a target motion signal in the opposite
      direction. Our results support the hypothesis that neuronal center-surround
      mechanisms contribute to the behavioral segregation of objects from the
      background.

PMID- 10896168
TI  - Olfactory functions are mediated by parallel and hierarchical processing.
AB  - How the human brain processes the perception, discrimination, and recognition of
      odors has not been systematically explored. Cerebral activations were therefore
      studied with PET during five different olfactory tasks: monorhinal smelling of
      odorless air (AS), single odors (OS), discrimination of odor intensity (OD-i),
      discrimination of odor quality (OD-q), and odor recognition memory (OM). OS
      activated amygdala-piriform, orbitofrontal, insular, and cingulate cortices and
      right thalamus. OD-i and OD-q both engaged left insula and right cerebellum. OD-q
      also involved other areas, including right caudate and subiculum. OM did not
      activate the insula, but instead, the piriform cortex. With the exception of
      caudate and subiculum, it shared the remaining activations with the OD-q, and
      engaged, in addition, the temporal and parietal cortices. These findings indicate
      that olfactory functions are organized in a parallel and hierarchical manner.

PMID- 10896169
TI  - The mechanism of interaction between visual flow and eye velocity signals for
      heading perception.
AB  - A translating eye receives a radial pattern of motion that is centered on the
      direction of heading. If the eye is rotating and translating, visual and
      extraretinal signals help to cancel the rotation and to perceive heading
      correctly. This involves (1) an interaction between visual and eye movement
      signals and (2) a motion template stage that analyzes the pattern of visual
      motion. Early interaction leads to motion templates that integrate head-centered
      motion signals in the visual field. Integration of retinal motion signals leads
      to late interaction. Here, we show that retinal flow limits precision of heading.
      This result argues against an early, vector subtraction type of interaction, but
      is consistent with a late, gain field type of interaction with eye velocity
      signals and neurophysiological findings in area MST of the monkey.

PMID- 10896170
TI  - Leptin: a multifunctional hormone.
AB  - Leptin is the protein product encoded by the obese (ob) gene. It is a circulating
      hormone produced primarily by the adipose tissue. ob/ob mice with mutations of
      the gene encoding leptin become morbidly obese, infertile, hyperphagic,
      hypothermic, and diabetic. Since the cloning of leptin in 1994, our knowledge in
      body weight regulation and the role played by leptin has increased substantially.
      We now know that leptin signals through its receptor, OB-R, which is a member of
      the cytokine receptor superfamily. Leptin serves as an adiposity signal to inform
      the brain the adipose tissue mass in a negative feedback loop regulating food
      intake and energy expenditure. Leptin also plays important roles in angiogenesis,
      immune function, fertility, and bone formation. Humans with mutations in the gene
      encoding leptin are also morbidly obese and respond to leptin treatment,
      demonstrating that enhancing or inhibiting leptin's activities in vivo may have
      potential therapeutic benefits.

PMID- 10896171
TI  - Human mu-opioid receptor overexpressed in Sf9 insect cells functionally coupled
      to endogenous Gi/o proteins.
AB  - Human mu-opioid receptor (HmuOR) with a tag of six consecutive histidines at its
      carboxyl terminus had been expressed in recombinant baculovirus infected Sf9
      insect cells. The maximal binding capacity for the [3H] diprenorphine and
      [3H]ohmefentanyl (Ohm) were 9.1 +/- 0.7 and 6.52 +/- 0.23 nmol/g protein,
      respectively. The [3H] diprenorphine or [3H] Ohm binding to the receptor
      expressed in Sf9 cells was strongly inhibited by mu-selective agonists [D-Ala2, N
      methyl-Phe4, glyol5]enkephalin (DAGO), Ohm, and morphine, but neither by delta
      nor by kappa selective agonist. Na+ (100 mM) and GTP (50 microM) could reduce
      HmuOR agonists etorphine and Ohm affinity binding to the overexpressed HmuOR. mu
      selective agonists DAGO and Ohm effectively stimulated [35S]GTP-gammaS binding
      (EC50 = 2.7 nM and 6.9 nM) and inhibited forskolin- stimulated cAMP accumulation
      (IC50 = 0.9 nM and 0.3 nM). The agonist-dependent effects could be blocked by
      opioid antagonist naloxone or by pretreatment of cells with pertussis toxin
      (PTX). These results demonstrated that HmuOR overexpressed in Sf9 insect cells
      functionally coupled to endogenous G(i/o) proteins.

PMID- 10896172
TI  - An electron microscopic-cytochemical localization of plasma membrane Ca(2+)
      ATPase activity in poplar apical bud cells during the induction of dormancy by
      short-day photoperiods.
AB  - Plasma membrane (PM) Ca2+-ATPase activity in poplar apical bud meristematic cells
      during short-day (SD)-induced dormancy development was examined by a cerium
      precipitation EM-cytochemical method. Ca2+-ATPase activity, indicated by the
      status of cerium phosphate precipitated grains, was localized mainly on the
      interior face (cytoplasmic side) of the PM when plants were grown under long days
      and reached a deep dormancy. A few reaction products were also observed on the
      nuclear envelope. When plant buds were developing dormancy after 28 to 42 d of SD
      exposure, almost no reaction products were present on the interior face of the
      PM. In contrast, a large number of cerium phosphate precipitated grains were
      distributed on the exterior face of the PM. After 70 d of SD exposure, when buds
      had developed a deep dormancy, the reaction products of Ca2+-ATPase activity
      again appeared on the interior face of the PM. The results seemed suggesting that
      two kinds of Ca2+-ATPases may be present on the PM during the SD-induced dormancy
      in poplar. One is the Ca2+-pumping ATPase, which is located on the interior face
      of the PM, for maintaining and restoring the Ca2+ homeostasis. The other might be
      an ecto-Ca2+-ATPase, which is located on the exterior face of the PM, for the
      exocytosis of cell wall materials as suggested by the fact of the cell wall
      thickening during the dormancy development in poplar.

PMID- 10896173
TI  - The expression of glucose regulated protein-94 in colorectal carcinoma cells
      treated by sodium butyrate.
AB  - The expression of glucose regulated protein 94 (GRP94) during the treatment of
      human colorectal carcinoma cell line-Clone A cells with sodium butyrate was
      studied. Sodium butyrate (SB) can cause functional and morphological effects on
      Clone A cells including growth arrest at G0/G1 stage and cell differentiation as
      observed by morphological changes, MTT and flow cytometry assays, as well as
      reduced Grp94 gene expression as shown by Northern blot and Western blot assays.
      The possible mechanism of the correlation between Grp94 gene expression and tumor
      growth inhibition and cell differentiation is briefly discussed.

PMID- 10896174
TI  - Nuclear assembly of purified Crythecodinium cohnii chromosomes in cell-free
      extracts of Xenopus laevis eggs.
AB  - Incubation of dinoflagellate Crythecodinium cohnii chromosomes in cytoplasmic
      extracts of unfertilized Xenopus laevis eggs resulted in chromosomes
      decondensation and recondensation, nuclear envelope assembly, and nuclear
      reconstitution. Dinoflagellate Crythecodinium cohnii is a kind of primitive
      eukaryote which possesses numerous permanently condensed chromosomes and
      discontinuous double-layered nuclear membrane throughout the cell cycle. The
      assembled nuclei, being surrounded by a continuous double membrane containing
      nuclear pores and the uniformly dispersed chromatin fibers are morphologically
      distinguishable from that of Dinoflagellate Crythecodinium cohnii. However,
      incubation of dinoflagellate Crythecodinium cohnii chromosomes in the extracts
      from dinoflagellate Crythecodinium cohnii cells does not induce nuclear
      reconstitution.

PMID- 10896175
TI  - Activation of phospholipase D activity in transforming growth factor-beta-induced
      cell growth inhibition.
AB  - Cells regulate phospholipase D (PLD) activity in response to numerous
      extracellular signals. Here, we investigated the involvement of PLD activity in
      transforming growth factor-beta (TGF-beta1)-mediated growth inhibition of
      epithelial cells. TGF-beta1 inhibits the growth of MDCK, Mv1Lu, and A-549 cells.
      In the presence of 0.4% butanol, TGF-beta1 induces an increase in the formation
      of phosphatidylbutanol, a unique product catalyzed by PLD. TGF-beta1 also induces
      an increase in phosphatidic acid (PA) level in A-549 and MDCK cells. TGF-beta1
      induces an increase in the levels of DAG labeled with [3H]-myristic acid in A-549
      and MDCK cells but not in Mv1Lu cells. No increase of DAG was observed in cells
      prelabeled with [3H]-arachidonic acid. The data presented suggest that PLD
      activation is involved in the TGF-beta1-induced cell growth inhibition.

PMID- 10896176
TI  - Leafy head formation of the progenies of transgenic plants of Chinese cabbage
      with exogenous auxin genes.
AB  - The experiment was performed to evaluate the progenies of plant lines transgenic
      for auxin synthesis genes derived from Ri T-DNA. Four lines of the transgenic
      plants were self-crossed and the foreign auxin genes in plants of T5 generation
      were confirmed by Southern hybridization. Two lines, D1232 and D1653, showed
      earlier folding of expanding leaves than untransformed line and therefore had
      early initiation of leafy head. Leaf cuttings derived from plant of transgenic
      line D1653 produced more adventitious roots than the control whereas the cuttings
      from folding leaves had much more roots than rosette leaves at folding stage, and
      the cuttings from head leaves had more roots than rosette leaves at heading
      stage. It is demonstrated that early folding of transgenic leaf may be caused by
      the relatively higher concentration of auxin. These plant lines with auxin
      transgenes can be used for the study of hormonal regulation in differentiation
      and development of plant organs and for the breeding of new variety with rapid
      growth trait.

PMID- 10896177
TI  - A commentary on brain-computer interfacing and its impact on rehabilitation
      science and clinical applicability.

PMID- 10896178
TI  - Brain-computer interface technology: a review of the first international meeting.
AB  - Over the past decade, many laboratories have begun to explore brain-computer
      interface (BCI) technology as a radically new communication option for those with
      neuromuscular impairments that prevent them from using conventional augmentative
      communication methods. BCI's provide these users with communication channels that
      do not depend on peripheral nerves and muscles. This article summarizes the first
      international meeting devoted to BCI research and development. Current BCI's use
      electroencephalographic (EEG) activity recorded at the scalp or single-unit
      activity recorded from within cortex to control cursor movement, select letters
      or icons, or operate a neuroprosthesis. The central element in each BCI is a
      translation algorithm that converts electrophysiological input from the user into
      output that controls external devices. BCI operation depends on effective
      interaction between two adaptive controllers, the user who encodes his or her
      commands in the electrophysiological input provided to the BCI, and the BCI which
      recognizes the commands contained in the input and expresses them in device
      control. Current BCI's have maximum information transfer rates of 5-25 b/min.
      Achievement of greater speed and accuracy depends on improvements in signal
      processing, translation algorithms, and user training. These improvements depend
      on increased interdisciplinary cooperation between neuroscientists, engineers,
      computer programmers, psychologists, and rehabilitation specialists, and on
      adoption and widespread application of objective methods for evaluating
      alternative methods. The practical use of BCI technology depends on the
      development of appropriate applications, identification of appropriate user
      groups, and careful attention to the needs and desires of individual users. BCI
      research and development will also benefit from greater emphasis on peer-reviewed
      publications, and from adoption of standard venues for presentations and
      discussion.

PMID- 10896179
TI  - The mental prosthesis: assessing the speed of a P300-based brain-computer
      interface.
AB  - We describe a study designed to assess a brain-computer interface (BCI),
      originally described by Farwell and Donchin [9] in 1988. The system utilizes the
      fact that the rare events in the oddball paradigm elicit the P300 component of
      the event-related potential (ERP). The BCI presents the user with a matrix of 6
      by 6 cells, each containing one letter of the alphabet. The user focuses
      attention on the cell containing the letter to be communicated while the rows and
      the columns of the matrix are intensified. Each intensification is an event in
      the oddball sequence, the row and the column containing the attended cell are
      "rare" items and, therefore, only these events elicit a P300. The computer thus
      detects the transmitted character by determining which row and which column
      elicited the P300. We report an assessment, using a boot-strapping approach,
      which indicates that an off line version of the system can communicate at the
      rate of 7.8 characters a minute and achieve 80% accuracy. The system's
      performance in real time was also assessed. Our data indicate that a P300-based
      BCI is feasible and practical. However, these conclusions are based on tests
      using healthy individuals.

PMID- 10896180
TI  - A direct brain interface based on event-related potentials.
AB  - Cross-correlation between a trigger-averaged event-related potential (ERP)
      template and continuous electrocorticogram was used to detect movement-related
      ERP's. The accuracy of ERP detection for the five best subjects (of 17 studied),
      had hit percentages >90% and false positive percentages <10%. These cases were
      considered appropriate for operation of a direct brain interface.

PMID- 10896181
TI  - Linear classification of low-resolution EEG patterns produced by imagined hand
      movements.
AB  - Electroencephalograph (EEG)-based brain-computer interfaces (BCI's) require on
      line detection of mental states from spontaneous EEG signals. In this framework,
      surface Laplacian (SL) transformation of EEG signals has proved to improve the
      recognition scores of imagined motor activity. The results we obtained in the
      first year of an European project named adaptive brain interfaces (ABI) suggest
      that: 1) the detection of mental imagined activity can be obtained by using the
      signal space projection (SSP) method as a classifier and 2) a particular type of
      electrodes can be used in such a BCI device, reconciling the benefits of SL
      waveforms and the need for the use of few electrodes. Recognition of mental
      activity was attempted on both raw and SL-transformed EEG data from five healthy
      people performing two mental tasks, namely imagined right and left hand
      movements.

PMID- 10896182
TI  - A virtual reality testbed for brain-computer interface research.
AB  - Virtual reality promises to extend the realm of possible brain-computer interface
      (BCI) prototypes. Most of the work using electroencephalograph (EEG) signals in
      VR has focussed on brain-body actuated control, where biological signals from the
      body as well as the brain are used. We show that when subjects are allowed to
      move and act normally in an immersive virtual environment, cognitive evoked
      potential signals can still be obtained and used reliably. A single trial
      accuracy average of 85% for recognizing the differences between evoked potentials
      at red and yellow stop lights will be presented and future directions discussed.

PMID- 10896183
TI  - The thought translation device (TTD) for completely paralyzed patients.
AB  - The thought translation device trains locked-in patients to self-regulate slow
      cortical potentials (SCP's) of their electroencephalogram (EEG). After operant
      learning of SCP self-control, patients select letters, words or pictograms in a
      computerized language support program. Results of five respirated, locked-in
      patients are described, demonstrating the usefulness of the thought translation
      device as an alternative communication channel in motivated totally paralyzed
      patients with amyotrophic lateral sclerosis.

PMID- 10896184
TI  - Brain-computer interface research at the Neil Squire Foundation.
AB  - The ultimate goal of our research is to utilize voluntary motor-related
      potentials recorded from the scalp in a direct Brain Computer Interface for
      asynchronous control applications. This type of interface will allow an
      individual with a high-level impairment to have effective and sophisticated
      control of devices such as wheelchairs, robotic assistive appliances, computers,
      and neural prostheses.

PMID- 10896185
TI  - Work toward real-time control of a cortical neural prothesis.
AB  - Implantable devices that interact directly with the human nervous system have
      been gaining acceptance in the field of medicine since the 1960's. More recently,
      as is noted by the FDA approval of a deep brain stimulator for movement
      disorders, interest has shifted toward direct communication with the central
      nervous system (CNS). Deep brain stimulation (DBS) can have a remarkable effect
      on the lives of those with certain types of disabilities such as Parkinson's
      disease, Essential Tremor, and dystonia. To correct for many of the motor
      impairments not treatable by DBS (e.g. quadriplegia), it would be desirable to
      extract from the CNS a control signal for movement. A direct interface with motor
      cortical neurons could provide an optimal signal for restoring movement. In order
      to accomplish this, a real-time conversion of simultaneously recorded neural
      activity to an online command for movement is required. A system has been
      established to isolate the cellular activity of a group of motor neurons and
      interpret their movement-related information with a minimal delay. The real-time
      interpretation of cortical activity on a millisecond time scale provides an
      integral first step in the development of a direct brain-computer interface
      (BCI).

PMID- 10896186
TI  - Direct control of a computer from the human central nervous system.
AB  - We describe an invasive alternative to externally applied brain-computer
      interface (BCI) devices. This system requires implantation of a special electrode
      into the outer layers of the human neocortex. The recorded signals are
      transmitted to a nearby receiver and processed to drive a cursor on a computer
      monitor in front of the patient. Our present patient has learned to control the
      cursor for the production of synthetic speech and typing.

PMID- 10896187
TI  - Parallel man-machine training in development of EEG-based cursor control.
AB  - A new parallel man-machine training approach to brain-computer interface (BCI)
      succeeded through a unique application of machine learning methods. The BCI
      system could train users to control an animated cursor on the computer screen by
      voluntary electroencephalogram (EEG) modulation. Our BCI system requires only two
      to four electrodes, and has a relatively short training time for both the user
      and the machine. Moving the cursor in one dimension, our subjects were able to
      hit 100% of randomly selected targets, while in two dimensions, accuracies of
      approximately 63% and 76% was achieved with our two subjects.

PMID- 10896188
TI  - Applications of cortical signals to neuroprosthetic control: a critical review.
AB  - Cortical signals might provide a potential means of interfacing with a
      neuroprosthesis. Guidelines regarding the necessary control features in terms of
      both performance characteristics and user requirements are presented, and their
      implications for the design of a first generation cortical control interface for
      a neuroprosthesis are discussed.

PMID- 10896189
TI  - A natural basis for efficient brain-actuated control.
AB  - The prospect of noninvasive brain-actuated control of computerized screen
      displays or locomotive devices is of interest to many and of crucial importance
      to a few 'locked-in' subjects who experience near total motor paralysis while
      retaining sensory and mental faculties. Currently several groups are attempting
      to achieve brain-actuated control of screen displays using operant conditioning
      of particular features of the spontaneous scalp electroencephalogram (EEG)
      including central mu-rhythms (9-12 Hz). A new EEG decomposition technique,
      independent component analysis (ICA), appears to be a foundation for new research
      in the design of systems for detection and operant control of endogenous EEG
      rhythms to achieve flexible EEG-based communication. ICA separates multichannel
      EEG data into spatially static and temporally independent components including
      separate components accounting for posterior alpha rhythms and central mu
      activities. We demonstrate using data from a visual selective attention task that
      ICA-derived mu-components can show much stronger spectral reactivity to motor
      events than activity measures for single scalp channels. ICA decompositions of
      spontaneous EEG would thus appear to form a natural basis for operant
      conditioning to achieve efficient and multidimensional brain-actuated control in
      motor-limited and locked-in subjects.

PMID- 10896190
TI  - Brain-computer interfaces based on the steady-state visual-evoked response.
AB  - The Air Force Research Laboratory has implemented and evaluated two brain
      computer interfaces (BCI's) that translate the steady-state visual evoked
      response into a control signal for operating a physical device or computer
      program. In one approach, operators self-regulate the brain response; the other
      approach uses multiple evoked responses.

PMID- 10896191
TI  - EEG-based communication: a pattern recognition approach.
AB  - We present an overview of our research into brain-computer interfacing (BCI).
      This comprises an offline study of the effect of motor imagery on EEG and an
      online study that uses pattern classifiers incorporating parameter uncertainty
      and temporal information to discriminate between different cognitive tasks in
      real-time.

PMID- 10896192
TI  - Current trends in Graz Brain-Computer Interface (BCI) research.
AB  - This paper describes a research approach to develop a brain-computer interface
      (BCI) based on recognition of subject-specific EEG patterns. EEG signals recorded
      from sensorimotor areas during mental imagination of specific movements are
      classified on-line and used e.g. for cursor control. In a number of on-line
      experiments, various methods for EEG feature extraction and classification have
      been evaluated.

PMID- 10896193
TI  - The effects of self-movement, observation, and imagination on mu rhythms and
      readiness potentials (RP's): toward a brain-computer interface (BCI).
AB  - Current movement-based brain-computer interfaces (BCI's) utilize spontaneous
      electroencephalogram (EEG) rhythms associated with movement, such as the mu
      rhythm, or responses time-locked to movements that are averaged across multiple
      trials, such as the readiness potential (RP), as control signals. In one study,
      we report that the mu rhythm is not only modulated by the expression of self
      generated movement but also by the observation and imagination of movement. In
      another study, we show that simultaneous self-generated multiple limb movements
      exhibit properties distinct from those of single limb movements. Identification
      and classification of these signals with pattern recognition techniques provides
      the basis for the development of a practical BCI.

PMID- 10896194
TI  - Brain-computer interface research at the Wadsworth Center.
AB  - Studies at the Wadsworth Center over the past 14 years have shown that people
      with or without motor disabilities can learn to control the amplitude of mu or
      beta rhythms in electroencephalographic (EEG) activity recorded from the scalp
      over sensorimotor cortex and can use that control to move a cursor on a computer
      screen in one or two dimensions. This EEG-based brain-computer interface (BCI)
      could provide a new augmentative communication technology for those who are
      totally paralyzed or have other severe motor impairments. Present research
      focuses on improving the speed and accuracy of BCI communication.

PMID- 10896195
TI  - A binary spelling interface with random errors.
AB  - An algorithm for design of a spelling interface based on a modified Huffman's
      algorithm is presented. This algorithm builds a full binary tree that allows to
      maximize an average probability to reach a leaf where a required character is
      located when a choice at each node is made with possible errors. A means to
      correct errors (a delete-function) and an optimization method to build this
      delete-function into the binary tree are also discussed. Such a spelling
      interface could be successfully applied to any menu-orientated alternative
      communication system when a user (typically, a patient with devastating
      neuromuscular handicap) is not able to express an intended single binary
      response, either through motor responses or by using of brain-computer
      interfaces, with an absolute reliability.

PMID- 10896196
TI  - Cycling by means of functional electrical stimulation.
AB  - The goal of this paper was the development of an optimized stimulation pattern of
      leg muscles that would allow paraplegic subjects to perform the movement of
      pedaling and thereby to drive a tricycle by means of functional electrical
      stimulation (FES). To obtain maximum average power output with minimum muscle
      force, the start, duration and amplitude of the stimulation signal applied to the
      individual muscles had to be optimized depending on the pedaling frequency. For
      the basic theoretical investigations the rider-tricycle system was modeled as a
      rigid body system on which the muscle forces are applied as joint moments. The
      muscles gluteus maximus, rectus femoris, vastii, and hamstrings were stimulated
      and the passive forces of some other muscles were considered. The modeling and
      simulation approach was then used to produce maximum power pedaling and steady
      state pedaling at 35 rpm. Hamstrings (41.9%) and vastii (35.8%) were the primary
      contributors to the optimization cost function of maximum power with minimum
      muscle loading. Based on these theoretical investigations an efficient
      stimulation pattern could be provided, taking into account the realistic
      possibilities of today's practical applications.

PMID- 10896197
TI  - Nerve cuff recordings of muscle afferent activity from tibial and peroneal nerves
      in rabbit during passive ankle motion.
AB  - Activity from muscle afferents regarding ankle kinesthesia was recorded using
      cuff electrodes in a rabbit preparation in which tactile input from the foot was
      eliminated. The purpose was to determine if such activity can provide information
      useful in controlling functional electrical stimulation (FES) systems that
      restore mobility in spinal injured man. The rabbit's ankle was passively flexed
      and extended while the activity of the tibial and peroneal nerves was recorded.
      Responses to trapezoidal stimulus profiles were investigated for excursions from
      10 degrees to 60 degrees using velocities from 5 degrees/s to 30 degrees/s and
      different initial ankle positions. The recorded signals mainly reflect activity
      from primary and secondary muscle afferents. Dorsiflexion stretched the ankle
      extensors and produced velocity dependent activity in the tibial nerve, and this
      diminished to a tonic level during the stimulus plateau. The peroneal nerve was
      silent during dorsiflexion, but was activated by stretch of the peroneal muscles
      during ankle extension. The responses of the two nerves behaved in a reciprocal
      manner, but exhibited considerable hysteresis, since motion that relaxed the
      stretch to the driving muscle produced an immediate cessation of the prior
      stretch induced activity. A noted difference between the tibial and peroneal
      nerve responses is that the range of joint position change that activated the
      flexor afferents was greater then for the extensor afferents. Ankle rotation at
      higher velocities increased the dynamic stretch evoked responses during the
      stimulus ramp but showed no effect on the tonic activity during the stimulus
      plateau. Prestretching the muscles by altering the initial position increased the
      response to the ramp movement, however, for the peroneal nerve, when the
      prestretch brought the flexor muscles near to their maximal lengths, the response
      to additional stretch provided by the ramp movement was diminished. The results
      indicate that the whole nerve recorded muscle afferent activity may be useful for
      control of FES assisted standing, because it can indicate the direction of
      rotation of the passively moved ankle joint, along with coarse information
      regarding the rate of movement and static joint position.

PMID- 10896198
TI  - Quantitative evaluation of two methods of control of bilateral stimulated hand
      grasps in persons with tetraplegia.
AB  - Electrical stimulation has been applied to the paralyzed muscles of both hands of
      two persons with tetraplegia using percutaneous and implantable electrodes. Two
      separate methods of user control were being investigated. The first monitored the
      myoelectric signals from the user's own sternocleidomastoid muscles and the
      second monitored wrist joint angle. These signals were used as commands to modify
      the stimulated grasps. The hands were instrumented to detect the degree of hand
      closure and grip force and the users matched these to specific target parameters
      using the controller during tracking tasks. Performance in these tracking tasks
      was measured quantitatively. Wrist control was found to be less sensitive to the
      direction of hand opening/closing required than the myoelectric control. The
      user's performance with the myoelectric control demonstrated sensitivity to the
      target size and the speed of hand movement in response to the command control.
      The wrist controller required less training than the myoelectric controller for
      users to become proficient in its use. Based on these results, the wrist
      controller and the myoelectric controller both provide successful control of
      bilateral hand grasp and release. Of the two controllers, the wrist controller is
      likely to provide the greater ease of use, although it is only available to the
      population of users with active wrist extension.

PMID- 10896199
TI  - The afferent neural response to electrotactile stimuli: preliminary results.
AB  - We recorded action potentials from three RA fibers innervating primate fingerpad,
      while applying electrotactile (electrocutaneous) stimulation. Negative pulses
      required 1.3-1.5 times more current than positive ones for entrainment. The
      strength-duration time constant was approximately 151 micros. Suprathreshold
      sinusoidal vibration synchronized to 30-Hz electrotactile pulses changed the
      electrotactile entrainment current slightly, indicating a possible electrical
      mechanical transduction interaction.

PMID- 10896200
TI  - Tissue factor and cancer procoagulant expressed by glioma cells participate in
      their thrombin-mediated proliferation.
AB  - The relationship between coagulation cascade activation and glioma cell
      proliferation was examined. The human glioma cell lines T98G, TM-1 and normal
      human astrocyte cell strain (NHA) were examined. Using anti-tissue factor (TF)
      antibody, immunocytochemical detection of TF antigen was obtained in both cell
      lines and cell strain. TF antigen in cell lysates was also measured by enzyme
      linked immunosorbent assay (ELISA). In a one-stage clotting assay, T98G, TM-1 and
      NHA revealed procoagulant activity (PCA) in normal human plasma and factor VII
      deficient plasma. PCA in normal human plasma was significantly inhibited by both
      inhibitory anti-TF antibody and cysteine protease inhibitor HgCl2. This result
      indicates that T98G, TM-1 and NHA cells express not only TF but also cancer
      procoagulant (CP) at the same time. In a cell proliferation assay, thrombin
      induced proliferation in T98G and TM-1 cells in a dose-dependent fashion and in
      NHA cell in a bell-shaped fashion. This mitogenic stimulant was inhibited by the
      specific thrombin inhibitor hirudin. The combinations of coagulation factors II,
      V, and X with or without factor VII induced proliferation in T98G, TM-1, and NHA
      cells. The maximal mitogenic stimulatory effects were larger in glioma cells than
      in NHA. These mitogenic stimulatory effects were also inhibited by hirudin. Each
      coagulation factor on its own or in any other combination of coagulation factors
      had no proliferative effect. Thus, these mitogenic stimulatory effects were
      considered to be the effect of thrombin. In conclusion, T98G and TM-1 human
      glioma cells express two different types of procoagulants TF and CP. In the
      presence of coagulation factors, these glioma cells can generate thrombin and
      this thrombin generation is capable of inducing glioma cell proliferation in
      vitro.

PMID- 10896201
TI  - Prognostic significance of endothelial surface score and MIB-1 labeling index in
      glioblastoma.
AB  - The aim of this study is to investigate the usefulness of a vascular endothelial
      surface score (VESS) and MIB-1 labeling index (MIB-1 LI), in a defined series of
      glioblastomas, as biological markers with prognostic significance of survival.
      Tumor tissue and survival were studied in a series of 38 patients with
      glioblastoma, previously treated by surgical resection and radiotherapy. For each
      tumor, immunohistochemical and morphometric studies were performed in order to
      study MIB-1 LI, and VESS, expressed as the CD-34 immunostained endothelial
      surface per 1000 tumor cells. The survival for the entire patient population of
      the series was 48.1+/-14.1 weeks, and the mean VESS for the tumors of the series
      ranged from 16.7 to 107 microm2 per 1000 tumor cells (mean: 38.7+/-18.2). Factors
      such as age or MIB-1 LI were not significatively associated with survival, but
      the median survival for the 18 patients with a VESS less than 35 was 50.7+/-3.7
      weeks, versus 45.9+/-2.8 weeks for the 20 patients showing a VESS higher than 36
      (p < 0.05). Our present results suggest that tumor VESS, expressed as the CD-34
      immunostained endothelial surface per each 1000 tumor cells, may have usefulness,
      as angiogenic-related factor influencing survival, in patients with glioblastoma.

PMID- 10896202
TI  - Analysis of the p300/CBP-Associated Factor (PCAF) gene in astrocytic tumors.
AB  - The PCAF gene encodes the p300/CBP-Associated Factor (PCAF), a histone
      acetyltransferase, which regulates p53 by acetylation of Lys320 in the C-terminal
      portion of p53. While the p53 gene is one of the most frequently mutated tumor
      suppressor genes in human tumors, such mutations occur in only 30% of astrocytic
      tumors. Since PCAF can regulate p53 activity, abrogation of PCAF function by PCAF
      gene mutation could be an alternate mechanism to inactivate the p53 pathway in
      tumors lacking p53 mutations. To test this hypothesis, we determined the
      nucleotide sequence of the entire PCAF coding region in 37 astrocytic tumors (17
      glioblastomas, 10 anaplastic astrocytomas, 7 low-grade astrocytomas, and 3
      pilocytic astrocytomas). We detected two single-nucleotide alterations that
      represented non-deleterious polymorphisms (GAG > GAA Glu103Glu, AAT > AGT
      Asn386Ser) but no obvious functional mutations. Moreover, the frequency of the
      Asn386Ser allele that contained Ser386 in glioma patients was not statistically
      different from its frequency in individuals without disease, and no significant
      association was observed between the PCAF polymorphisms and the presence or
      absence of p53 mutations in the tumors. We conclude that the PCAF gene is not
      mutated during the development of the astrocytic tumors studied here.

PMID- 10896203
TI  - A histopathological contribution to supratentorial glioma grading, definition of
      mixed gliomas and recognition of low grade glioma with Rosenthal fibers.
AB  - BACKGROUND: Previous glioma studies have described separate grading systems for
      oligodendrogliomas and astrocytomas. Many of these gliomas contain mixtures of
      neoplastic astrocytes and oligodendrocytes. Prognosis may be related to the
      percentages of these neoplastic components. Previous survival/grading studies
      have been limited to histopathological features but have not evaluated the
      importance of percentages of neoplastic components. This study attempted to
      perceive the relative importance of percentages of neoplastic astrocytes and
      oligodendrocytes for definition of astroglial, oligodendroglial and mixed
      oligoastroglial tumors. After determination of these limits we explored the
      possibility to develop a grading system for common supratentorial gliomas based
      on reproducible histopathological features. METHODS: A retrospective study was
      performed of 362 cases of unselected supratentorial glioma. One hundred and
      thirty-eight binary and nine continuous histopathological variables, amongst
      which percentages of neoplastic astrocytes and oligodendrocytes, were scored and
      related to survival. Only well reproducible histological features were accepted
      in Cox regression to define glioma grades. RESULTS AND CONCLUSIONS:
      Supratentorial gliomas appeared to be composed of variable percentages of
      neoplastic oligodendrocytes and astrocytes, but this spectrum did not correspond
      to a continuous change in prognosis. Gliomas containing 30% or more neoplastic
      oligodendrocytes had a slightly better outcome (p < 0.0432) but higher
      percentages did not further improve prognosis. Percentages of neoplastic
      astrocytes were not correlated to survival. We therefore propose to designate
      gliomas containing 30% or more neoplastic oligodendrocytes as oligodendroglial
      tumors, and others as astroglial tumors. From a prognostic point of view there is
      no need to recognize mixed oligoastrocytomas. An interesting finding was the
      recognition of a low grade glioma group with Rosenthal fibers, which had the
      longest postoperative survival. Another prognosticator of interest concerns the
      mitotic rate as a continuous variable. Atypical mitoses indicated the worst
      survival, after necrosis. It was possible to develop a grading system for all
      supratentorial gliomas using six reproducible histological parameters: necrosis,
      atypical mitoses, the mitotic rate, endothelial proliferative activity,
      percentage of neoplastic oligodendrocytes and Rosenthal fibers. This resulted in
      four grades for astroglial tumors (p < 0.002) and three grades for
      oligodendroglial tumors (p < 0.008) which differed significantly within each
      group with respect to survival.

PMID- 10896205
TI  - Radiosurgery of meningeal melanocytoma.
AB  - The authors present a case of meningeal melanocytoma arising from Meckel's cave.
      A coal-black, vascular tumor was partially removed by surgery.
      Histopathologically, the tumor lacked anaplastic features. Immunohistochemical
      studies confirmed that the tumor was of neuroectodermal origin and had low
      proliferating activity. The patient underwent gamma knife radiosurgery for the
      residual tumor, in which 25 Gy of radiation was delivered to the tumor margin.
      Three years after irradiation, the tumor showed marked shrinkage without
      complication.

PMID- 10896204
TI  - The peripheral benzodiazepine receptors: a review.
AB  - Peripheral benzodiazepine receptors (PBRs) have been identified in various
      peripheral tissues as well as in glial cells in the brain. This review describes
      the tissue and subcellular distribution of the PBR in mammalian tissues and
      analyzes its many putative endogenous ligands. It deals with the pharmacological,
      structural and molecular characterization of the PBR, the proteins associated
      with the receptor (VDAC, ANC, PRAX-1) and their roles in cell growth and
      differentiation, cancer, steroid biosynthesis, and other physiological roles.

PMID- 10896206
TI  - Brain tumor imaging with 99mTc-tetrofosmin: comparison with 201Tl, 99mTc-MIBI,
      and 18F-fluorodeoxyglucose.
AB  - The purpose of the present study was to assess the ability of technetium-99m
      tetrofosmin (99mTc-TF) to predict tumor malignancy and to compare its uptake with
      that of thallium-201 (201Tl), technetium-99m-hexakis-2-methoxyisobutyl isonitrile
      (99mTc-MIBI) and fluorine-18-fluorodeoxyglucose (18F-FDG) in brain tumors. 99mTc
      TF single-photon emission computed tomography (SPECT) imaging was performed in 22
      patients with brain tumors and 3 healthy controls. Some of the patients underwent
      201Tl (n = 12) and 99mTc-MIBI SPECT (n = 14) and 18F-FDG positron emission
      tomography (PET) (n = 12). The radioactivity ratio of tumor to contralateral
      normal tissue (T/N) and the ratio of tumor to contralateral white matter (T/WM)
      were calculated in SPECT and PET images, respectively. In healthy controls, 99mTc
      TF uptake was seen only in scalp, in the choroid plexus and pituitary gland, but
      not in normal cerebral parenchyma. TF T/N in low grade gliomas (2.8+/-0.4) was
      significantly lower than that in high grade gliomas (22.5+/-29.8) and malignant
      non-gliomas (8.3+/-2.8) without overlap of values (p = 0.003 and p = 0.014,
      respectively). TF T/N was significantly correlated with MIBI T/N (p = 0.92, p =
      0.001), Tl T/N (p = 0.72, p = 0.017), and FDG T/WM (p = 0.65. p = 0.031). There
      was an excellent agreement between TF T/N and MIBI T/N values on linear
      regression analysis (MIBI T/N = -0.63+/-0.97 x TF T/N). These preliminary results
      indicate that SPECT imaging with 99mTc-TF may be useful for the non-invasive
      grading of brain tumors. They also suggest that 99mTc-TF and 99mTc-MIBI may
      accumulate in brain tumors by a similar mechanism or in relation to a similar
      process of tumor cell proliferation.

PMID- 10896207
TI  - Prognostic value of the expression of tumor suppressor genes p53, p21, p16 and
      prb, and Ki-67 labelling in high grade astrocytomas treated with radiotherapy.
AB  - Cumulative inactivation of tumor suppressor genes and/or amplification of
      oncogenes lead to progressively more malignant astrocytic tumors. We have
      analyzed the significance of tumor suppressor genes p53, p21, p16 and
      retinoblastoma protein (pRb) and proliferative activity for survival in 77 high
      grade astrocytic tumors. After operation, the patients--25 anaplastic
      astrocytomas (AA) and 52 glioblastomas (GBs)--were treated with similar
      radiotherapy. The expression of the suppressor genes and the proliferative
      activity were analyzed immunohistochemically. p53 immunopositivity was found in
      44% of AAs and 46% of GBs. Tumors with aberrant p53 expression had lower
      proliferation indices than p53 immunonegative tumors. Neither p53 expression nor
      p21 immunonegativity (52% of AAs and 48% of GBs) correlated with survival. p16
      immunostaining was negative in 16% of AAs and in 44% of GBs, and it correlated
      inversely with survival in both uni- and multivariate analyses. pRb
      immunostaining was negative only in 8% of both AAs and GBs and the absence of p16
      and pRb were mutually exclusive. Ki-67 labelling index (LI) was significantly
      higher in GBs (26.8%) than in AAs (20.3%), and in multivariate analysis it was an
      independent prognostic factor for survival. In 48% of AAs Ki-67 LI exceeded 20%
      and this subset of AAs had similar prognosis as GB. In high grade astrocytic
      tumors p16 immunonegativity was an independent indicator of poor prognosis in
      addition to the previously established patient's age, histopathology and Ki-67
      LI. Furthermore, there was a subset of AAs with a high proliferation rate (> 20%)
      in which the histopathological hallmarks of GB were lacking, but which had
      similarly dismal prognosis as GB.

PMID- 10896208
TI  - Matrix metalloproteinase 2 (MMP-2) immunoreactive protein is associated with poor
      grade and survival in brain neoplasms.
AB  - Matrix metalloproteinases play an important role in the invasion of tumor cells
      and the progression of cancer. The 72 kDa type IV collagenase, a matrix
      metalloproteinase 2 (MMP-2) has been shown to contribute to the invasion and
      metastasis in diverse malignant neoplasms. OBJECT: To elaborate the potential
      role of MMP-2 in brain tumor invasion we studied the expression and localization
      of this enzyme protein in 101 brain tumors representing different types of brain
      neoplasms. For the first time, we also correlated the expression of MMP-2 protein
      to patient survival. METHODS: Using immunohistochemistry and a monoclonal
      antibody specific for MMP-2 we found that MMP-2 protein was primarily localized
      in tumor cells and vasculature cells as well as inflammatory cells. The
      expression of MMP-2 was absent or negligible in benign tumors (pilocytic
      astrocytoma and meningioma). Thirty-three percent (6/18) of astrocytomas, 38%
      (3/8) of anaplastic astrocytomas, 14% (1/7) of anaplastic oligodendrogliomas, 54%
      (19/35) of glioblastomas and 100% (6/6) of metastatic brain tumors were positive
      for MMP-2. A correlation between MMP-2 expression and survival was found in
      malignant brain tumors. The mean survival of patients with an MMP-2 negative
      tumor was 36 months, when it was only 7-14 months in patients with an MMP-2
      positive tumor. CONCLUSIONS: Our data suggest that MMP-2 is associated with
      histological malignancy and poor survival in brain tumors.

PMID- 10896209
TI  - Membrane targeting and translocation of bacterial hydrogenases.
AB  - Periplasmic or membrane-bound bacterial hydrogenases are generally composed of a
      small subunit and a large subunit. The small subunit contains a peculiar N
      terminal twin-arginine signal peptide, whereas the large subunit lacks any known
      targeting signal for export. Genetic and biochemistry data support the assumption
      that the large subunit is cotranslocated with the small subunit across the
      cytoplasmic membrane. Indeed, the signal peptide carried by the small subunit
      directs both the small and the large subunits to the recently identified Mtt/Tat
      pathway, independently of the Sec machinery. In addition, the twin-arginine
      signal peptide of hydrogenase is capable of directing protein import into the
      thylakoidal lumen of chloroplasts via the homologous deltapH-driven pathway,
      which is independent of the Sec machinery. Therefore, the translocation of
      hydrogenase shares characteristics with the deltapH-driven import pathway in
      terms of Sec-independence and requirement for the twin-arginine signal peptide,
      and with protein import into peroxisomes in a "piggyback" fashion.

PMID- 10896210
TI  - Molecular biology and regulation of methane monooxygenase.
AB  - Methanotrophs are ubiquitous in the environment and play an important role in
      mitigating global warming due to methane. They are also potentially interesting
      for industrial applications such as production of bulk chemicals or
      bioremediation. The first step in the oxidation of methane is the conversion to
      methanol by methane monooxygenase, the key enzyme, which exists in two forms: the
      cytoplasmic, soluble methane monooxygenase (sMMO) and the membrane-bound,
      particulate methane monooxygenase (pMMO). This paper reviews the biochemistry and
      molecular biology of both forms of MMO. In the past few years there have been
      many exciting new findings. sMMO components have been expressed in heterologous
      and homologous hosts. The pMMO has been purified and biochemically studied in
      some detail and the genes encoding the pMMO have been sequenced. Copper ions have
      been shown to play a key role in regulating the expression of both MMO enzyme
      complexes. We also present a model for copper regulation based on results from
      Northern analysis, primer-extensions and new sequence data, and raise a number of
      unanswered questions for future studies.

PMID- 10896211
TI  - The bidirectional hydrogenase of Synechocystis sp. PCC 6803 works as an electron
      valve during photosynthesis.
AB  - The activity of the bidirectional hydrogenase of the cyanobacterium Synechocystis
      sp. PCC 6803 was found not to be regulated in parallel to respiration but to
      photosynthesis. A mutant with a deletion in the large hydrogenase subunit gene
      (hoxH), which contains the active site, was impaired in the oxidation of
      photosystem I (PSI) when illuminated with light, which excites either PSI alone
      or both photosystems. The fluorescence of photosystem II (PSII) of this mutant
      was higher than that of wild-type cells. The transcript level of the
      photosynthetic genes psbA, psaA and petB was found to be different in the
      hydrogenase-free mutant cells compared to wild-type cells, which indicates that
      the hydrogenase has an effect on the regulation of these genes. Collectively,
      these results suggest that the bidirectional hydrogenase functions as a valve for
      low-potential electrons generated during the light reaction of photosynthesis,
      thus preventing a slowing down of electron transport. This conclusion is
      supported by growth curves demonstrating that the mutant cells need more time to
      adapt to changing light intensities. Investigations of the wild-type and
      deltahoxH strains strongly suggest that Synechocystis contains only the
      bidirectional hydrogenase, which seems to be essentially insensitive to oxygen.

PMID- 10896212
TI  - Chemical analysis of processing of spiralin, the major lipoprotein of Spiroplasma
      melliferum.
AB  - The plasma membrane of Spiroplasma melliferum contains a major membrane
      associated lipoprotein called spiralin. In this study, the processing pathway of
      spiralin was investigated by chemical analysis of the purified protein and by
      using [35S]cysteine, [35S]methionine, [14C]myristic acid (14C-14:0),
      [14C]palmitic acid (14C-16:0), and globomycin. SDS-PAGE analysis of membrane
      proteins showed the leader peptide cleavage of prospiralin and provided evidence
      for an apparent selectivity in the acylation: the unprocessed protein was
      labelled with 14C-16:0 only (O-ester-linked acyl chains), and the mature form
      with both 14C-labelled fatty acids (O-ester-linked + amide-linked chains).
      Chemical analysis of the purified protein revealed that spiralin contains S
      glycerylcysteine and is covalently modified with two O-ester-linked acyl chains
      and one amide-linked fatty acid chain. However, a specific selectivity in the O-
      and the N-acylations was not confirmed; palmitate and stearate were the major
      components. The amounts of O-ester- and amide-linked acyl chains, the resistance
      to Edman degradation and the presence of S-glycerylcysteine together indicate
      that spiralin is a "classical" lipoprotein (i.e. is triacylated) and is probably
      processed by a mechanism similar to that described for gram-negative eubacteria.
      On the basis of these findings, a biogenesis pathway for spiralin is proposed.

PMID- 10896213
TI  - Molecular analysis of an outer membrane protein, MopB, of Methylococcus
      capsulatus (Bath) and structural comparisons with proteins of the OmpA family.
AB  - The gene encoding a major outer membrane protein (MopB) of the methanotroph
      Methylococcus capsulatus (Bath) was cloned and sequenced. The cloned DNA
      contained an open reading frame of 1044 bp coding for a 348-amino-acid
      polypeptide with a 21-amino-acid leader peptide. Comparative sequence analysis of
      the predicted amino acid sequence revealed that the C-terminal part of MopB
      possessed sequences that are conserved in the OmpA family of proteins. The N
      terminal half of the protein had no significant sequence similarity to other
      proteins in the databases, but the predicted secondary structure showed stretches
      of amphipathic beta-strands typical of transmembrane segments of outer membrane
      proteins. A region with four cysteines similar to the cysteine-encompassing
      region of the OprF of Pseudomonas aeruginosa was found toward the C-terminal part
      of MopB. Results from whole-cell labeling with the fluorescent thiol-reacting
      reagent 5-iodoacetamidofluorescein indicated a surface-exposed location for these
      cysteines. A probe consisting of the 3'-end of the mopB gene hybridized to the
      type I methanotroph Methylomonas methanica S in Southern blots containing DNA
      from nine methanotrophic strains representing six different genera.

PMID- 10896214
TI  - Growth phase and metal-dependent regulation of the dpsA gene in Synechococcus sp.
      strain PCC 7942, USA.
AB  - The Synechococcus sp. strain PCC 7942 dpsA gene encodes a stress-inducible DNA
      binding protein whose transcription increases in the stationary phase. Such
      transcription is likely under the control of an alternative sigma factor. Our
      current work indicated that dpsA transcription is also important under metal-ion
      limitation, because dpsA mRNA levels increased 12-fold under low-iron conditions,
      and that dpsA function is essential for growth under iron-limiting conditions.
      Promoter activity of the dpsA-promoter-lacZ reporter gene constructs implied that
      a region of dyad symmetry centered 28 nucleotides from the transcription start is
      required for metal-dependent repression, as judged by the level of lacZ induction
      following treatment of cultures with the chelator 2,2'-dipyridyl. This potential
      operator sequence is distinct from the site recognized by the cyanobacterial Fur
      repressor homologue. No other nutrient stresses (nitrogen, sulfur, phosphorus)
      yielded the high level of induction seen following chelator treatment. These
      studies suggest that there may be more than one class of metal-dependent
      repressor in cyanobacteria.

PMID- 10896215
TI  - Cellular localization and metabolic function of n-butylamine-induced amine
      oxidases in the fungus Aspergillus niger AKU 3302.
AB  - Using transmission electron microscopy, the amine oxidase activity in Aspergillus
      niger AKU 3302 was localized to the outer side of the cell wall but not inside
      the cell using the cerium perhydroxide deposition method. The presence of cerium
      in the deposit was confirmed by energy-dispersive microanalysis of X-rays.
      Interestingly, immunocytochemical localization using gold labeling with a
      specific antibody indicated the presence of amine oxidase protein inside the cell
      wall and not only on the outer surface. Besides labeling of the cell wall, a high
      level of labeling was also observed inside the cell in what seemed to be
      secretory vesicle structures. It is proposed that the highly active amine oxidase
      AO-I is located in the cell wall and serves primarily as a detoxifying agent,
      preventing amines from entering and damaging the cell. The amine oxidation
      exhibits an interesting spatial orientation involving a release of toxic hydrogen
      peroxide into the extracellular space. The inactive amine oxidase protein located
      inside the cell is most probably the amine oxidase AO-II, found in cell
      homogenates. It is also likely that the less active AO-II is an improperly folded
      precursor of AO-I, which acquired low-level activity after cell homogenization in
      the presence of Cu(II) and oxygen due to autooxidative formation of topaquinone.

PMID- 10896216
TI  - Regulation of nitrogenase activity in Rhodobacter capsulatus under dark microoxic
      conditions.
AB  - Rhodobacter capsulatus modulates its in vivo nitrogenase activity in the light in
      response to the addition of NH4+ in a variety of ways: with ADP-ribosylation of
      the Fe-protein of nitrogenase, with a switch-off response that is independent of
      ADP-ribosylation, and with a "magnitude response." In the light, these responses
      are differentially shown by cultures that differ in the degree of their nitrogen
      limitation. Here we examined the response of these culture types to the addition
      of NH4+ under dark, microoxic conditions and found that all three responses can
      be observed under these conditions. However, the magnitude response was much more
      sensitive to the ammonium concentration, and the ADP-ribosylation response
      correlated only poorly with activity changes, similar to results obtained in the
      light. In contrast to previous reports, Fe-protein was not ADP-ribosylated in
      response to the presence of oxygen.

PMID- 10896217
TI  - Effect of metal complexation on the bioavailability of nitrilotriacetic acid to
      Chelatobacter heintzii ATCC 29600.
AB  - Many polluted sites contain a mixture of organics and heavy metals.
      Nitrilotriacetic acid has been chosen as a model organic compound to study the
      effect of metal binding on organic bioavailability and degradation of organics.
      The effect of varying the ratio of metal to nitrilotriacetic acid on its
      utilisation has been examined using the gram-negative bacterium Chelatobacter
      heintzii ATCC 29600. The following parameters of substrate utilisation were
      examined: growth, degradation, respiration, mineralisation and nitrilotriacetic
      acid uptake. Complexation of nitrilotriacetic acid by Cu(II), Ni(II), Co(II) and
      Zn(II) prevented utilisation of nitrilotriacetic acid by C. heintzii;
      complexation to Fe(III) or Mn(II) did not. The pattern of inhibition was
      consistent with a 1:1 stoichiometry of metal binding to nitrilotriacetic acid.
      Inhibition was not due to metal ion toxicity, but was a result of metal
      nitrilotriacetic acid complexes being recalcitrant to degradation. In addition,
      the effect of complexing (phosphate) and non-complexing (PIPES) buffers on
      bioavailability was examined: Co and Zn prevented degradation of nitrilotriacetic
      acid in PIPES buffer, but not in phosphate buffer. This was due to the removal of
      Co and Zn from solution by phosphate precipitation, leaving nitrilotriacetic acid
      uncomplexed. The results demonstrated that metal-organic complexation can alter
      the bioavailability of organic pollutants and may also modulate the toxicity of
      heavy metals.

PMID- 10896218
TI  - Analysis of promoter sequences from Lactobacillus and Lactococcus and their
      activity in several Lactobacillus species.
AB  - Promoter-active fragments were isolated from the genome of the probiotic organism
      Lactobacillus rhamnosus strain GG using the promoter-probe vector pNZ272. These
      promoter elements, together with a promoter fragment isolated from the vaginal
      strain Lactobacillus fermentum BR11 and two previously defined promoters
      (Lactococcus lactis and Lactobacillus acidophilus ATCC 4356 slpA), were
      introduced into three strains of Lactobacillus. Primer-extension analysis was
      used to map the transcriptional start site for each promoter. All promoter
      fragments tested were functional in each of the three lactobacilli and a purine
      residue was used to initiate transcription in most cases. The promoter elements
      encompassed a 52- to 1,140-fold range in promoter activity depending on the host
      strain. Lactobacillus promoters were further examined by surveying previously
      mapped sequences for conserved base positions. The Lactobacillus hexamer regions
      (-35: TTgaca and -10: TAtAAT) closely resembled those of Escherichia coli and
      Bacillus subtilis, with the highest degree of agreement at the -10 hexamer. The
      TG dinucleotide upstream of the -10 hexamer was conserved in 26% of Lactobacillus
      promoters studied, but conservation rates differed between species. The region
      upstream of the -35 hexamer of Lactobacillus promoters showed conservation with
      the bacterial UP element.

PMID- 10896219
TI  - Menaquinol oxidase activity and primary structure of cytochrome bd from the amino
      acid fermenting bacterium Corynebacterium glutamicum.
AB  - Cytochrome d was spectroscopically detected in membrane fractions of the amino
      acid-fermenting, high-G+C gram-positive bacterium Corynebacterium glutamicum.
      Inhibition of NADH oxidase activity in the membranes by cyanide suggested that
      the main terminal respiratory oxidase during the stationary phase was a type of
      cytochrome bd. Cytochrome bd-type quinol oxidase, purified from the membranes,
      was composed of two subunits. Its reduced form showed absorption peaks at 627,
      595, and 560 nm, which were due to haem d, high-spin protohaem, and low-spin
      protohaem, respectively. The air-oxidised form showed a peak at 645 nm, which
      might be due to oxygenated ferrous haem d. The spectral features and the size of
      subunit I are more similar to the properties of cytochromes bd from
      Proteobacteria, such as Escherichia coli, than to those of cytochrome bd from low
      G+C gram-positive bacteria, such as Bacillus stearothermophilus. The menaquinol
      oxidase activity of the purified cytochrome bd was low, but was enhanced about
      fivefold by pre-incubating the enzyme with menaquinones. The order of
      effectiveness of quinols as oxidase substrates was clearly different from that of
      quinones as the activators of enzyme activity. Furthermore, activation was
      destroyed by ultraviolet irradiation of the pre-incubated enzyme and then
      restored by a second incubation with menaquinone. These results indicate that the
      enzymatic properties of this new oxidase are more similar to the properties of
      cytochromes bd from low-G+C gram-positive bacterial than to those of
      proteobacterial counterparts. They also suggest that the enzyme has a second
      quinone-binding site essential for full activity, in addition to the active
      centre for substrate oxidation. By using probes based on partial peptide
      sequences of the subunits, the genes for the two subunits of C. glutamicum
      cytochrome bd were cloned. The deduced amino acid sequence demonstrated that
      subunit I lacks the C-terminal half of the Q loop and that the primary structure
      of C. glutamicum cytochrome bd is more similar to that of other gram-positive
      bacteria than to proteobacterial cytochromes bd.

PMID- 10896220
TI  - CO2-dependent fermentation of phenol to acetate, butyrate and benzoate by an
      anaerobic, pasteurised culture.
AB  - Fermentative degradation of phenol was studied using a non-methanogenic,
      pasteurised enrichment culture containing two morphologically different bacteria.
      Phenol was fermented to benzoate, acetate and butyrate and their relative
      occurrence depended on the concentration of hydrogen. Proportionately more
      benzoate was formed with high initial levels of H2. The influence of PH2 on the
      fermentation pattern was studied both in dense cell suspensions and in growing
      cultures by addition of hydrogen. An increase in growth yield (OD578) was
      observed, compared to controls, as a consequence of phenol degradation; however,
      the increase was less in H2-amended treatments, in which most of the phenol ended
      up as benzoate. The degradation of phenol in the dense cell suspension
      experiments was dependent on CO2. Benzoate was not degraded when added as a
      substrate to the growing culture. This is, to our knowledge, the first report
      concerning the fermentative degradation of phenol to nonaromatic products.

PMID- 10896221
TI  - Stigmatella aurantiaca Sg a15 carries genes encoding type I and type II 3-deoxy-D
      arabino-heptulosonate-7-phosphate synthases: involvement of a type II synthase in
      aurachin biosynthesis.
AB  - 3-Deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthases catalyse the first
      step of the shikimate pathway. Two unrelated DAHP synthase types have been
      described in plants and bacteria. Two type II (aroA(A2) and aroA(A5)) and one
      type I DAHP synthase gene (aroA001) were identified from the myxobacterium
      Stigmatella aurantiaca Sg a15. Inactivation of aroA(A5) leads to a mutant that is
      impaired in the biosynthesis of aurachins, which are electron transport
      inhibitors and contain an anthranilate moiety. Feeding of anthranilic acid to the
      mutant culture restores production of aurachins. Inactivation of aroA(A2) and
      aroA001 does not impair production of aurachins or other known secondary
      metabolites of S. aurantiaca Sg a15.

PMID- 10896222
TI  - PhrA, the major photoreactivating factor in the cyanobacterium Synechocystis sp.
      strain PCC 6803 codes for a cyclobutane-pyrimidine-dimer-specific DNA photolyase.
AB  - A new broad-host-range plasmid, pSL1211, was constructed for the over-expression
      of genes in Synechocystis sp. strain PCC 6803. The plasmid was derived from
      RSF1010 and an Escherichia coli over-expression plasmid, pTrcHisC. Over-expressed
      protein is made with a removable N-terminal histidine tag. The plasmid was used
      to over-express the phrA gene and purify the gene product from Synechocystis sp.
      strain PCC 6803. PhrA is the major ultraviolet-light-resistant factor in the
      cyanobacterium. The purified PhrA protein exhibited an optical absorption
      spectrum similar to that of the cyclobutane pyrimidine dimer (CPD) DNA photolyase
      from Synechocuccus sp. strain PCC 6301 (Anacystis nidulans). Mass spectrometry
      analysis of PhrA indicated that the protein contains 8-hydroxy-5-deazariboflavin
      and flavin adenine dinucleotide (FADH2) as cofactors. PhrA repairs only
      cyclobutane pyrimidine dimer but not pyrimidine (6-4) pyrimidinone photoproducts.
      On the basis of these results, the PhrA protein is classified as a class I, HDF
      type, CPD DNA photolyase.

PMID- 10896223
TI  - Carotenoids of an Antarctic psychrotolerant bacterium, Sphingobacterium
      antarcticus, and a mesophilic bacterium, Sphingobacterium multivorum.
AB  - The major carotenoid pigments of an Antarctic psychrotolerant bacterium,
      Sphingobacterium antarcticus, and a mesophilic bacterium, Sphingobacterium
      multivorum, were identified as zeaxanthin, beta-cryptoxanthin, and beta-carotene.
      Analysis was based on ultraviolet-visible spectroscopy, mass spectroscopy, and
      reversed-phase HPLC. Photoacoustic spectroscopy of intact bacterial cells
      revealed that the bulk of the pigments in S. antarcticus and S. multivorum was
      associated with the cell membrane. In vitro studies with synthetic membranes of
      phosphatidylcholine demonstrated that the major pigment was bound to the
      membranes and decreased their fluidity. The relative amounts of polar pigments
      were higher in cells grown at 5 degrees C than in cells grown at 25 degrees C. In
      the mesophilic strain, the synthesis of polar carotenoids was quantitatively less
      than that of the psychrotolerant strain.

PMID- 10896224
TI  - Dimethylsulfone as a growth substrate for novel methylotrophic species of
      Hyphomicrobium and Arthrobacter.
AB  - Dimethylsulfone is a major product of the chemical oxidation in the atmosphere of
      the principal biogenic sulfur gas, dimethylsulfide, but no studies have been
      reported on the mechanisms for its microbiological degradation. Three novel
      strains of bacteria have been isolated from enrichment cultures provided with
      dimethylsulfone as the only carbon and energy substrate. These are novel
      facultatively methylotrophic species of Hyphonmicrobium and Arthobacter, capable
      of growth on a range of one-carbon substrates. Cell-free extracts contained
      activities of enzymes necessary for a reductive/oxidative pathway for
      dimethylsulfone degradation: membrane-bound-dimethylsulfone and dimethylsulfoxide
      reductases, dimethylsulfide monooxygenase, and methanethiol oxidase. Enzymatic
      evidence is also presented for the subsequent oxidation of formaldehyde by
      formaldehyde and formate dehydrogenases in the Hyphomicrobium strain and by a
      dissimilatory ribulose monophosphate cycle in the Arthrobacter strains. The
      strains also grew on dimethylsulfoxide and dimethylsulfide, and dimethylsulfide
      grown bacteria oxidized dimethylsulfide and dimethylsulfoxide but not
      dimethylsulfone. Formaldehyde assimilation was effected in the Hyphomicrobium
      strain by the serine pathway, but enzymes of the ribulose monophosphate cycle for
      formaldehyde assimilation were present in the Arthrobacter strains grown on
      dimethylsulfone. In contrast, one of the Arthrobacter strains was shown to switch
      to the serine pathway during growth on methanol. Growth yields on dimethylsulfone
      and formaldehyde were consistent with the occurrence of the serine pathway in
      Hyphomicrobium strain S1 and the ribulose monophosphate cycle in Arthrobacter
      strain TGA, and with the proposed reductive pathway for dimethylsulfone
      degradation in both.

PMID- 10896225
TI  - Characterization of the Sinorhizobium meliloti genes encoding a functional
      dihydrodipicolinate synthase (dapA) and dihydrodipicolinate reductase (dapB).
AB  - In bacteria, the known pathways for diaminopimelate (DAP) and lysine biosynthesis
      share two key enzymes, dihydrodipicolinate synthase and dihydrodipicolinate
      reductase, encoded by the dapA and dapB genes, respectively. In rhizobia, these
      genes have not yet been genetically characterized. In this work, by sequence
      analysis, we identified two divergent open reading frames on the 140-MDa plasmid
      pRmeGR4b of Sinorhizobium meliloti strain GR4. Termed dapA and dapB, these encode
      products which show significant sequence similarities to DapA and DapB proteins,
      respectively. Escherichia coli DAP auxotrophs (dapA and dapB mutants) could be
      complemented with the pRmeGR4b dapA and dapB genes, indicating that these genes
      code for functional dihydrodipicolinate synthase and dihydrodipicolinate
      reductase, respectively. Reverse-transcriptase PCR analyses and beta
      galactosidase assays using transcriptional dapA-lacZ and dapB-lacZ fusions
      suggest that these genes are constitutively expressed in S. meliloti. The dapA
      and dapB genes are not widely distributed in S. meliloti and appear to be
      specific for strains carrying pRmeGR4b-type plasmids.

PMID- 10896226
TI  - Novel glycoproteins of the halophilic archaeon Haloferax volcanii.
AB  - Archaea possess many eukaryote-like properties, including the ability to
      glycosylate proteins. Using oligosaccharide staining and lectin binding, this
      study revealed the existence of several glycosylated Haloferax volcanii membrane
      proteins, besides the previously reported surface layer (S-layer) glycoprotein.
      While the presence of glycoproteins in archaeal S-layers and flagella is well
      documented, few archaeal glycoproteins that are not part of these structures have
      been reported. The glycosylated 150, 98, 58 and 54 kDa protein species detected
      were neither precursors nor breakdown products of the 190 kDa S-layer
      glycoprotein. Furthermore, these novel glycoproteins were outwardly oriented and
      intimately associated with the membrane.

PMID- 10896227
TI  - Tissue factor in neutrophils.

PMID- 10896228
TI  - The RsaI polymorphism in the alpha-fibrinogen gene and response of plasma
      fibrinogen to physical training--a controlled randomised clinical trial in men.
AB  - We have previously reported cross-sectional data on an interaction effect between
      physical activity and alpha-fibrinogen RsaI polymorphism on fibrinogen in
      postmenopausal women. In the present controlled randomised study, we investigated
      the role of the RsaI polymorphism in determining the response of fibrinogen to
      long-term regular exercise. Middle-aged men (n = 140), randomly selected from the
      population registry, were randomised into an exercise or a reference group for a
      3-year low intensity exercise intervention. Complete data were available in 125
      men. The RsaI restriction enzyme detects threonine (Thr) to alanine change in the
      fibrinogen alpha codon 312. Anaerobic ventilatory threshold increased by 4%, but
      decreased by 2% in the exercise and reference groups, respectively. Mean
      fibrinogen did not decrease in either study group. However, in the exercise
      group, individual changes in anaerobic threshold explained 48% of the variance in
      fibrinogen changes in the Thr homozygotes. Our data offer a new aspect of
      beneficial effects of regular physical exercise on risk factors for coronary
      heart disease.

PMID- 10896229
TI  - Treatment with interferon plus ribavirin in anti-HIV negative patients with
      congenital coagulation disorders and chronic hepatitis C.
AB  - BACKGROUND: Hepatitis C virus (HCV) infected hemophiliacs respond at low rate to
      interferon (IFN) monotherapy. AIMS: To assess efficacy of IFN and RBV in HIV
      negative hemophiliacs with chronic hepatitis C and identify early predictive
      factors of response. METHODS: Twenty naive patients were treated with interferon
      and RBV for twelve months. Response was assessed by both serial ALT and HCV RNA
      levels. RESULTS: Normalization of ALT with clearance of HCV RNA occurred in seven
      (35%) patients. Age and age at infection were the only features associated with a
      higher likelihood of response. In all responders the viral load had decreased by
      at least one log within two months of starting treatment. CONCLUSIONS:
      Combination of interferon and ribavirin is well tolerated by hemophiliacs who
      achieve similar sustained response rates to non-hemophiliacs. Quantitative
      assessment of viral load at two months of treatment is a useful method to
      identify non-responders at an early stage.

PMID- 10896230
TI  - Sucrose formulated recombinant human antihemophilic factor VIII is safe and
      efficacious for treatment of hemophilia A in home therapy--International Kogenate
      FS Study Group.
AB  - To add an increased level of safety to antihemophilic factor replacement therapy,
      a full-length, recombinant Factor VIII (rFVIII) product has been developed
      without human-derived plasma proteins during purification and formulation and
      using an additional solvent/detergent viral inactivation step. This first
      clinical trial of a sucrose-formulated full-length rFVIII (rFVIII-FS) was
      conducted in previously treated patients (> or = 100 prior exposure days) with
      severe (<2% FVIII) hemophilia A in North America (NA) and Europe (EU).
      Pharmacokinetic profiles for rFVIII-FS were compared with those of currently
      licensed rFVIII product (Kogenate) in 35 patients. Safety and efficacy during
      home therapy were evaluated in 71 patients. The new formulation displayed a
      pharmacokinetic profile similar to that of rFVIII. Patients on home therapy
      received a cumulative total of 11,867 exposure days, 12,546 infusions, and
      22,443,694 IU of rFVIII-FS. Of 2585 bleeds, 93.5% were treated with 1-2 infusions
      and 80.5% of responses were rated as excellent or good. No evidence of de novo
      inhibitor formation was observed. Only 0.27% of infusions were associated with
      any drug-related adverse event. Except for an episode of intermittent chest pain
      with palpitations which ceased after treatment with analgesics, associated
      adverse events were mild or moderate. Overall, rFVIII-FS provided excellent
      hemostatic control, was well-tolerated, and caused no significant adverse
      effects, thus demonstrating safety and efficacy for treatment of bleeds in
      patients with hemophilia A.

PMID- 10896231
TI  - Venous thrombotic risk in family members of unselected individuals with factor V
      Leiden.
AB  - The factor V Leiden mutation (FVL) leads to a seven-fold increased risk of venous
      thromboembolism (VTE). In thrombophilic families. 25% of carriers have
      experienced thrombosis before the age of 40 years. Aim of our study was to assess
      the association of FVL with VTE in first-degree family members of unselected
      symptomatic and asymptomatic carriers of FVL. We tested 197 relatives of
      consecutive thrombosis patients with FVL and 36 relatives of asymptomatic
      carriers on the presence of FVL and the occurrence of VTE. The incidence of VTE
      in relatives with FVL of symptomatic carriers was 0.34%/year. This was similar to
      the incidence in relatives with FVL of asymptomatic carriers. Kaplan Meier
      analysis in relatives of symptomatic propositi showed that at the age of 58
      years, thrombosis-free survival was reduced to 75% in carriers and 93% in non
      carriers (P <0.05). Carriers of FVL had a three times higher thrombotic risk than
      non-carriers. In combination with environmental risk factors, FVL clearly adds to
      the risk of VTE. The thrombotic incidence rate in these unselected relatives with
      FVL. however, is considerably lower than was seen in carriers of thrombophilic
      families (1.7%/year). Therefore, special care should be paid to individuals with
      a positive family history of venous thrombosis while exposed to these risk
      factors.

PMID- 10896232
TI  - Prevalence of factor V Leiden in patients with myocardial infarction and normal
      coronary angiography.
AB  - Factor V Leiden is associated with an increased risk of venous thrombosis and
      myocardial infarction in young women, but not in men in this latter case. The aim
      of this study was to evaluate the prevalence of this mutation in patients with
      myocardial infarction but normal coronary angiography. We compared 3 groups of
      patients: one group consisted of 107 patients with premature myocardial
      infarction but no significant coronary artery stenosis; another group of 244
      patients with myocardial infarction and significant coronary artery stenosis; a
      third group of 400 healthy controls. Factor V Leiden was found in 13 patients
      (12.1%) who had a myocardial infarction without significant coronary artery
      stenosis, 11 patients (4.5%) who had a myocardial infarction with significant
      coronary artery stenosis (p = 0.01) and in 20 controls (5%) (p = 0.01). Odds
      ratio associated with factor V Leiden were respectively 2.93 (CI95: 1.18-7.31 )
      and 2.63 (CI95: 1.19-5.78) when we compared myocardial infarction patients
      without significant coronary artery stenosis to controls or to patients with
      significant coronary artery stenosis. In myocardial infarction patients without
      significant coronary artery stenosis, prevalence of factor V Leiden is
      significantly higher than in controls. This new finding supports the hypothesis
      that thrombosis plays a key role in this selected situation.

PMID- 10896233
TI  - Tissue factor and homocysteine levels in ischemic heart disease are associated
      with angiographically documented clinical recurrences after coronary angioplasty.
AB  - BACKGROUND: In ischemic heart disease (IHD) patients high plasma levels of Tissue
      Factor (TF), the trigger of coagulation cascade, are present. Homocysteine (Hcy)
      is a risk factor for coronary artery disease, and several different
      pathophysiological mechanisms by which Hcy may play a role in thrombus formation
      have been postulated in "in vitro" studies. We investigated the "in vivo" role of
      Hcy in affecting plasma levels of TF, its inhibitor Tissue Factor Pathway
      Inhibitor (TFPI) and hypercoagulability. METHODS AND RESULTS: We investigated 119
      IHD patients who underwent PTCA and compared them with 103 healthy subjects. TF,
      TFPI, Thrombin-Antithrombin complexes (TAT) and Hcy levels were significantly
      higher in the patients than in the controls. A positive correlation was found
      between Hcy and TF (r = 0.54; p < 0.0001), Hcy and TFPI (r = 0.26; p <0.05) as
      well as Hcy and TAT (r = 0.33; p <0.0001) levels. An inverse correlation existed
      between folate intake and Hcy levels (r = -0.28; p = 0.001). Hcy levels within
      the first quartile and in the highest quartile were associated with a lower (p <
      0.001) and higher (p <0.0001) rate of clinical recurrences, respectively.
      Patients with TF values in the first quartile had a lower rate of
      angiographically documented clinical recurrences as compared to those in the
      fourth quartile (p <0.01); those in the highest quartile of TF showed a higher
      rate of recurrences (p = 0.001). Multivariate analysis confirmed these results
      (first quartile of Hcy: OR 0.02, C1 0.002-0.27; fourth quartile of Hcy: OR 36.5,
      C1 3.6-365/first quartile of TF: OR 0.006, C1 0.001-0.44; fourth quartile of TF:
      OR 16.4, C1 3.0 - 90.0), also after adjustment for risk factors and Hcy and TF
      respectively. CONCLUSIONS: In this study we show that TF, TFPI and TAT levels are
      correlated with Hcy plasma levels in IHD patients, providing evidence of an "in
      vivo" pathophysiological mechanism of hyperhomocysteinemia. The observed
      association between angiographically documented clinical recurrences and TF and
      Hcy values awaits confirmation in studies designated to evaluate this issue on a
      larger number of patients.

PMID- 10896234
TI  - Humanized severe combined immunodeficient mice as a potential model for the study
      of tolerance to factor VIII.
AB  - A Severe Combined Immunodeficient (SCID) mouse model has been established to
      evaluate experimental conditions leading to the production of factor VIII (FVIII)
      autoantibodies. To this end, we humanized 10 groups of 7 mice with peripheral
      blood mononuclear cells of 10 unrelated healthy blood donors (15 x 10(6)
      cells/mouse). Mice were injected with saline or immunized i.p. with 50 IU of a
      plasma derived human FVIII 24 h after reconstitution. Further immunization was
      made with 25 IU of FVIII every fortnight during 6 weeks and animals were
      sacrificed after 8 weeks. All reconstituted mice showed a spontaneous production
      of anti-FVIII antibodies in the absence of immunization with the corresponding
      antigen. However, no differences were observed regarding the quantity or the
      quality of these antibodies produced in the immunized or the saline group,
      indicating that tolerance to FVIII had been transferred with cell reconstitution.
      Affinity purified FVIII specific antibodies were capable of inhibiting FVIII
      activity and preventing the binding of FVIII to phospholipids in a dose-dependent
      manner. Immunoprecipitation experiments showed that the antibodies recognized
      only the C1 and C2 light chain domains. Since antibodies of interest can be found
      in the SCID mouse model and, moreover, since they are qualitatively comparable
      with the source donor's antibodies, this model provides a tool to study the
      regulation of tolerance against self antigens in normal subjects and in acquired
      haemophilia patients.

PMID- 10896236
TI  - Relationship between factor VIII mutation type and inhibitor development in a
      cohort of previously untreated patients treated with recombinant factor VIII
      (Recombinate). Recombinate PUP Study Group.
AB  - A cohort of 79 previously untreated patients (PUPs) with moderate-severe
      haemophilia A (baseline Factor VIII < or =2%) were enrolled in a study to
      evaluate the safety, efficacy and immunogenicity of recombinant factor VIII (r
      FVIII, Recombinate). Blood samples were obtained retrospectively from a total 55
      PUPs who were investigated for the spectrum of FVIII gene mutations responsible
      for their haemophilia. FVIII gene inversion mutations were found in 27 (49%)
      patients. Two patients had partial gene deletions. The remaining 26 patients were
      then screened for mutations in the FVIII gene coding region using conformation
      sensitive gel electrophoresis. Point mutations were identified in 22 (85%) of the
      patients and 14 of these mutations were novel. Study subjects were monitored for
      the development of FVIII inhibitors throughout the study. A total of 23 of the 73
      evaluable subjects (including one subject with a low inhibitor titer at baseline)
      demonstrated an inhibitor on one or more occasions; 11 (15%) were persistent.
      Inhibitors were detected in patients with partial gene deletions and inversions
      and in three of eight patients with missense mutations. No inhibitors were found
      in 11 patients with small insertions or deletions resulting in an alteration of
      the protein translation reading frame (frameshift mutations). The results
      corroborate the observation that mutation type is an important determinant of the
      propensity to develop inhibitory anti-FVIII antibody.

PMID- 10896235
TI  - Prothrombotic risk factors in children with acute lymphoblastic leukemia treated
      with delayed E. coli asparaginase (COALL-92 and 97 protocols).
AB  - Hereditary prothrombotic risk factors have been shown to increase the risk of
      venous thrombosis in children treated with the combination of E. coli
      asparaginase and steroids. In the present study the role of prothrombotic risk
      factors in children with ALL treated according to the COALL study protocol was
      investigated in 108 consecutively recruited childhood patients. The prevalence
      rates of prothrombotic risk factors [factor V G1691A mutation, the prothrombin
      G20210A variant, the TT677 methylenetetrahydrofolate reductase genotype,
      deficiencies of protein C, protein S, antithrombin, elevated lipoprotein (a)] in
      this cohort were within the range reported for healthy Caucasians, and comparable
      to previously reported data for other leukemic patients. Venous thromboembolism
      occurred in 3 of the 108 children (induction n = 1; reinduction n = 2: 2.8%), and
      none of these children carried a prothrombotic risk factor. The results of the
      present study, suggest that the role of hereditary and acquired disturbances of
      coagulation in the development of thromboses might depend on the treatment
      regimen.

PMID- 10896237
TI  - A computer generated induction system for hospitalized patients starting on oral
      anticoagulant therapy.
AB  - There is an increasing use of computer-based dosage programs to monitor oral
      anticoagulant therapy in outpatients. DAWN AC INDUCTION by 4S, UK, is a computer
      generated system to initiate oral anticoagulant therapy providing fast access to
      the maintenance program. This method of initiation of anticoagulant therapy has
      not been validated. We therefore randomized 50 hospitalized patients starting
      oral anticoagulation to control by the computer and 51 by manual dosing using a
      dosing schedule based on a locally defined algorithm. After a 7 days follow up,
      the daily mean INR was 2.09 and 2.07 and the proportion of dose adjustments was
      48% and 45% in the computer and manually controlled groups respectively. Twenty
      eight % of the patients monitored by the computer system required at least one
      manual overriding. DAWN AC INDUCTION provided a simple and accurate organization
      of the data, with an overall quality comparable to that of the manual system.
      Furthermore, the induction programme provided simple access to the maintenance
      programme. Although it required careful monitoring, the programme resulted in a
      significant saving in personnel time.

PMID- 10896238
TI  - Enhanced tissue factor pathway activity and fibrin turnover in the alveolar
      compartment of patients with interstitial lung disease.
AB  - Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity
      pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and
      sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar
      hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant
      activity (PCA), tissue factor (TF) activity and F VII activity were assessed by
      means of specific recalcification assays. The overall fibrinolytic activity (FA)
      was measured using the (125)I-labeled fibrin plate assay. Fibrinopeptide A (FP
      A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type
      (t-PA), PA-inhibitor I (PAI-1) and alpha2-antiplasmin (alpha2-AP) were determined
      by ELISA technique. As compared to Controls, all groups with interstitial lung
      disease (ILD) displayed an increase in BALF PCA by approximately one order of
      magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F
      VII-activity was increased in all ILD groups, and elevated FP-A levels were
      noted. There was no significant difference in procoagulant activities between the
      different ILD entities, but the increase in TF was significantly correlated with
      deterioration of lung compliance. Overall fibrinolytic activity did not
      significantly differ between ILD entities and Controls, although some reduction
      in IPF subjects was observed. Nevertheless, changes in the profile of the
      different pro- and antifibrinolytic compounds were noted. U-PA, but not t-PA
      levels were significantly reduced in all ILD groups. alpha2-AP was markedly
      elevated throughout, whereas PAI-1 levels were lowered. As a balance of

PMID- 10896239
TI  - Induction of tissue factor expression in whole blood: lack of evidence for the
      presence of tissue factor expression in granulocytes.
AB  - The present investigation was undertaken to explore the effect of platelets,
      tumor necrosis factor (TNF) and phorbel ester [phorbol 12-myristate 13-acetate
      (PMA)] on lipopolysaccharide (LPS)-induced tissue factor (TF) activity and TF
      antigen by using Western blot and ELISA-techniques. LPS was found to induce
      correlating levels of TF antigen and the activity in monocytes. TNF and PMA, when
      used alone, failed to induce TF activity and the antigen in monocytes, but
      enhanced the LPS-induced TF activity and the antigen by 2 to 3-fold. Addition of
      platelet rich plasma to isolated blood cells enhanced the LPS-induced TF activity
      but not the antigen levels in monocytes. In contrast to whole platelets, platelet
      lysates enhanced both LPS-induced TF activity and the antigen. Granulocytes
      isolated from heparinized plasma incubated for 2 or 24 h with LPS alone or
      together with PMA, failed to generate TF antigen or the activity. Although
      granulocyte preparations isolated from whole blood that was incubated for 24 h
      with LPS and PMA apparently possessed a significant amount of TF activity and the
      antigen, this could be accounted for by trace levels of contaminating monocytes.
      Upregulation of LPS-induced TF activity but not the antigen by platelets in the
      presence of granulocytes suggests that the increased TF activity could be the
      result of PS enrichment of monocytes by fusion or platelets with activated
      monocytes.

PMID- 10896240
TI  - Aspirin potentiates LPS-induced fibrin formation (FPA) and TNF-alpha-synthesis in
      whole blood.
AB  - The effect of aspirin on LPS-incubation of whole blood was investigated. Aspirin
      induced a concentration dependent increase (2.5-5-fold at 5 mM aspirin) in LPS
      induced appearance of TNF-alpha and fibrinopeptide A (FPA) in plasma, despite the
      concomitant increase in the inhibitory cytokine IL-100. Aspirin substantially
      raised the levels of LPS-induced TF-mRNA and TNFalpha-mRNA in monocytes isolated
      from whole blood. The median ratio for TF-/beta-actin mRNA increased from 1.5 +/-
      0.44 in the presence of LPS-alone, to 2.5 +/- 0.51 when 5 mM aspirin was added.
      The TNFalpha/beta-actin mRNA ratios were 1.8 +/- 0.4 and 5.5 +/- 2.7
      respectively. Addition of exogenous PGE2 before incubation nearly abrogated the
      effect of aspirin on TNF-alpha, substantiating the role of PGE2 as a regulator of
      TNF-alpha synthesis, whereas the effect on FPA was small. Thus, in the presence
      of LPS in this whole blood model, aspirin apparently had a pro-inflammatory
      rather than an anti-inflammatory effect.

PMID- 10896241
TI  - A monoclonal antibody raised against human beta-factor XIIa which also recognizes
      alpha-factor XIIa but not factor XII or complexes of factor XIIa with C1 esterase
      inhibitor.
AB  - A monoclonal antibody (mAb 2/215) against human beta-factor XIIa (beta-FXIIa),
      was shown by equilibrium binding studies to have a high affinity for alpha-factor
      XIIa (alpha-FXIIa) (Kd 1.8 nM) and beta-FXIIa (Kd 0.65 nM) but no detectable
      reaction with FXII zymogen or alpha-FXIIa:C1 esterase inhibitor (C1-INH) complex.
      Surface plasmon resonance studies showed that the mAb 2/215 bound to immobilized
      alpha-FXIIa with high affinity (KD 3.93 +/- 1.46 x 10(-11) M). Western blots
      employing mAb 2/215 indicated that human plasma contained small amounts of alpha
      FXIIa but no beta-FXIIa. mAb 2/215 did not inhibit the amidolytic activity of
      beta-FXIIa and protected beta-FXIIa from inhibition by C1-INH. The recovery by
      ELISA,employing mAb 2/215 as the capture antibody, of alpha-FXIIa added to plasma
      was 11.3%, 42% after inhibition of alpha-FXIIa with 3:4dichloroisocoumarin, and
      82% when 0.5% Triton-X100 was added to the assay. Gel filtration showed that the
      majority of plasma alpha-FXIIa existed as a complex (Mr approximately 170,000).
      This distinctive mAb increases the capacity to study the contact system in health
      and disease.

PMID- 10896242
TI  - In vivo penetration of experimentally produced clots by monoclonal antibodies.
AB  - Antifibrin monoclonal antibodies show potential as clot targeting agents for
      diagnosis and possibly therapy in thrombotic disease. To be effective the
      antibody must bind to the fibrin component of the clot. The ability of two
      antifibrin mabs (NIB 1H10 and NIB 12B3) to penetrate occlusive clots in vivo was
      investigated. Both mabs react with human fibrin but not with human fibrinogen nor
      with the fibrin or fibrinogen from the species used in this study. Two
      heterologous animal (sheep and rabbit) thrombus models were used. Clots in both
      cases were made within isolated vein segments using a mixture of human and native
      fibrinogen. The clots in sheep veins were observed radiographically and found to
      be occlusive for a mean of 4.2 +/- 2.2 days and thereafter appeared only
      partially occlusive. When targeted in their occlusive phase (131)I labelled mab
      accumulated in the clot reaching a maximum ratio of 1.82 +/- 0.42 when compared
      to counts in homologous sheep clots in the contralateral limb. It was confirmed
      in the rabbit jugular vein model that total occlusivity did not prevent antibody
      accumulation in the heterologous clot by injecting the fibrin specific mab 1H10
      and examining the clot excised after 1, 6 and 24 h using immunofluorescence. In a
      further series of similar experiments (125)I labelled mab 1H10 was used and
      detected using autoradiography. Both sets of experiments indicated that
      penetration of occlusive clots by the antibody occurred and that considerable
      accumulation was present at 6 and 24 h. The results indicate that a circulating
      antibody can readily gain access to experimentally produced clots in occluded
      veins.

PMID- 10896243
TI  - Demonstration of an association between Chlamydia pneumoniae infection and venous
      thromboembolic disease.
AB  - Chlamydia pneumoniae infection has been linked to atherosclerosis, but a possible
      relationship with venous thromboembolism (VTE) has not been sought. We determined
      circulating anti-C. pneumoniae antibody levels in patients with VTE. We studied
      176 case patients with objectively diagnosed VTE and 197 age- and sex-matched
      healthy controls, in a retrospective study. Acquired risk factors for VTE and
      frequent predisposing genetic factors (factor V Arg 506 Gln and factor II G 20210
      A mutations) were assessed in all the subjects. Anti-C. pneumoniae IgG antibodies
      were determined by microimmunofluorescence. All positive plasma samples (titer >
      or =128) were precisely quantified and tested for the presence of specific IgM
      antibodies. Fifty-four percent of the cases and 15.9% of the controls had
      specific IgG titers of at least 256 (p <0.0001). The crude odds ratio for VTE was
      6.2 (95% CI, 3.8-10.1), and rose to 7.7 (4.5-13.2) after excluding subjects
      carrying the factor V Arg 506 Gln or factor II G 20210 A mutations. The odds
      ratio for VTE increased with the IgG titer: the adjusted odds ratios were 2.1
      (95% CI, 1.1-4.1), 5.3 (2.7-10.6) and 33.0 (4.4-248.4) for titers of 256, 512 and
      1024, respectively. Only one subject (a case patient) with a high IgG titer (> or
      =256) also had specific IgM. High titers of anti-C. pneumoniae IgG antibodies are
      frequently found in patients with previous venous thromboembolism. This
      association deserves to be confirmed in other case-control studies and
      prospective studies.

PMID- 10896244
TI  - Clinical evaluation of a monoclonal antibody-based enzyme immunoassay for fibrin
      degradation products in patients with clinically suspected pulmonary embolism.
      ANTELOPE-Study Group.
AB  - We prospectively evaluated the diagnostic accuracy of the Fibrinostika FbDP assay
      in 304 consecutive patients with suspected pulmonary embolism and examined
      potentially useful cut-off points at which the disease can be excluded. The
      prevalence of pulmonary embolism was 31%. The assay generated an area under the
      Receiver Operating Characteristic curve of 0.79 (95% CI 0.73-0.84). A cut-off
      point of 0.05 microg/ml yielded a sensitivity, specificity, negative predictive
      value and an exclusion efficiency of 100% (95% CI 96-100), 5% (95% CI 2-9), 100%
      (95% CI 69-100) and 3% (95% CI 2-6), respectively. A clinically useful cut-off
      point seems to be 0.11 microg/ml which corresponded with a sensitivity,
      specificity, negative predictive value and an exclusion efficiency of 96% (95% CI
      90-99), 27% (95% CI 24-28), 93% (95% CI 84-98) and 20% (95% CI 16-25),
      respectively. We conclude that the assay has potential clinical utility for the
      exclusion of pulmonary embolism, but it cannot be used as a sole test.

PMID- 10896245
TI  - The Bbeta-sheet in the PAI-1 molecule plays an important role for its stability.
AB  - We have investigated the B beta-sheet in PAI-1 regarding its role for the
      stability of the molecule. The residues from His(219) to Tyr(241) (except for
      Gly(230) and Pro(240)), covering the s2B and s3B strands, and in addition
      His(185) and His(190)) were substituted by amino acids with opposite properties.
      The 23 generated single-site changed mutants and also wild type PAI-1 (wtPAI-1)
      were expressed in E. coli. Subsequently they were purified by heparin-Sepharose
      and anhydrotrypsin agarose affinity chromatographies. The stability of the
      purified PAI-1 variants was analyzed at 37 degrees C and at different pHs (5.5,
      6.5 or 7.5). At pH 7.5 and 37 degrees C, single substitutions of the residues in
      the central portions of both strands 2 and 3 in the B beta-sheet (Ile(223) to
      Leu(226) on s2B and Met(235) to Ile(237) on s3B), caused a significant decrease
      in stability, yielding half-lives of about 10-25% as compared to wtPAI-1. On the
      other hand, mutations at both sides of the central portion of the B beta-sheet
      (Tyr(221), Asp(222), Tyr(228) and Thr(232)) frequently resulted in an increased
      PAI-1 stability (up to 7-fold). While wtPAI-1 exhibited prolonged half-lives at
      pH 6.5 and 5.5, the PAI-1 variant Y228S was more stable at neutral pH (half-life
      of 9.6 h at pH 7.5) as compared to its half-life at pH 5.5 (1.1 h). One of the 4
      modified histidine residues (His(229)) resulted in a variant with a clearly
      affected stability as a function of pH, suggesting that it may, at least in part,
      be of importance for the pH dependence of the PAI-1 stability. Thus, our data
      demonstrate that the B beta-sheet is of great importance for the stability of the
      molecule. Modifications in this part causes decreased or increased stability in a
      certain pattern, suggesting effects on the insertion rate of the reactive center
      loop into the A beta-sheet of the molecule.

PMID- 10896246
TI  - Plasma TAFI antigen variations in healthy subjects.
AB  - The Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a recently described
      inhibitor of fibrinolysis. The physiological variations of plasma TAFI antigen
      are not well known. We studied TAFI antigen values in healthy populations with a
      commercially available kit from Milan Analytica (Switzerland). Broad range of
      TAFI antigen values (from 41% to 259%) was found in a population of 249 healthy
      individuals. Gender as well as pregnancy did not influence mean values of TAFI
      antigen. There was a positive correlation between TAFI antigen and age in female
      (r = 0.28; p <0.05) but not in male populations. Mean TAFI antigen value of a
      black African male group [mean +/- SD (range): 87 +/- 23 (39-144%)] was
      significantly lower than the one of age matched Caucasian men [114 +/- 34 (52
      259%)] (p <0.0001). TAFI antigen values were very stable within individuals, they
      did not significantly vary on day time or at several months period. Thus, in
      contrast to large inter-individual variations, TAFI antigen levels are quite
      stable within individuals.

PMID- 10896247
TI  - Elastase mediated fibrinolysis in acute promyelocytic leukemia.
AB  - The bleeding syndrome of acute promyelocytic leukemia (APL) is complex and
      consists of disseminated intravascular coagulation (DIC) and hyperfibrinolysis.
      Elastase, derived from malignant promyelocytes, is believed to mediate the
      fibrinogeno- and fibrinolysis by aspecific proteolysis. In this study we measured
      the role of elastase in fifteen patients with APL by using an assay for elastase
      degraded fibrin(ogen) and the results were compared with those obtained in
      patients with sepsis induced DIC. High levels of elastase were observed in sepsis
      and APL. The levels of fibrinogen and fibrin degradation products were
      significantly higher in APL patients compared to patients with sepsis induced
      DIC. Nevertheless, the level of elastase degraded fibrin(ogen) was higher in the
      sepsis group (635.3 ng/ml, compared to 144.3 ng/ml in APL; p <0.0001). So, the
      enormous increase in fibrin and fibrinogen degradation products in APL cannot be
      explained by elastase activity. This study suggests a minor role for elastase
      mediated proteolysis in the hemorrhagic diathesis in APL patients.

PMID- 10896248
TI  - Proteolytic modulation of thrombopoietin activity: comparison of thrombin,
      plasmin, and urokinase.
AB  - Several observations suggest that limited proteolysis of full-length 70 kD human
      thrombopoietin (Tpo) may be important for Tpo biology. Recently, it was reported
      that thrombin cleaves full-length recombinant human Tpo (rhTpo) sequentially at
      two sites, Arg(195) within the glycan domain followed by Arg(117) within the
      cytokine domain, and that these cleavages modulate Tpo activity in vitro. We
      demonstrate that urokinase and plasmin also cleave rhTpo in a time-dependent
      manner. Urokinase cleavage is confined to the glycan domain, and generates a 35
      kD N-terminal fragment that contains the intact cytokine domain, and is
      associated with increased Tpo activity. In contrast, plasmin cleaves Tpo
      sequentially at two specific sites (Arg(205) within the glycan domain followed by
      Lys(52) within the cytokine domain), and is associated with a marked decrease in
      Tpo activity. These proteolytic events have potential implications for regulation
      of Tpo activity in vivo.

PMID- 10896249
TI  - Incomplete inhibition of platelet aggregation and glycoprotein IIb-IIIa receptor
      blockade by abciximab: importance of internal pool of glycoprotein IIb-IIIa
      receptors.
AB  - Resting platelets contain a substantial internal pool of GPIIb-IIIa complexes
      that is exposed on the surface of activated platelets. Whether the exposure of
      internal GPIIb-IIIa complexes on the activated platelet surface affects therapy
      with GPIIb-IIIa antagonists is poorly understood. We addressed this issue in
      thirteen patients who underwent elective coronary stenting and received
      abciximab. Platelet aggregation, surface expression of GPIIb-IIIa and P-selectin,
      receptor blockade of GPIIb-IIIa, and platelet release in response to ADP and
      thrombin-receptor activating peptide (TRAP) were determined ex vivo by Lumi
      aggregometry and flow cytometry before, during and after abciximab
      administration. We found that inhibition of aggregation and GPIIb-IIIa blockade
      of ADP-stimulated platelets was almost complete during abciximab administration.
      In contrast, when TRAP was used to stimulate platelets ex vivo aggregation was
      only partially inhibited, most likely due to release of internal pool of
      unblocked GPIIb-IIIa complexes. Using electron microscopy we found that 7E3
      occupied GPIIb-IIIa complexes are internalized into the surface connected system
      (SCS) and the alpha-granules of washed platelets which was associated with a
      reduced degranulation of the alpha-granula membrane protein P-selectin. We
      conclude, that despite internalization of abciximab into the internal pool of
      GPIIb-IIIa, upon strong platelet activation with thrombin a significant amount of
      unblocked internal GPIIb-IIIa can be exposed on the platelet surface and mediate
      platelet aggregation. Incomplete blockade of the internal GPIIb-IIIa pool may
      limit clinical efficacy of abciximab.

PMID- 10896250
TI  - Platelets release thrombopoietin (Tpo) upon activation: another regulatory loop
      in thrombocytopoiesis?
AB  - Thrombopoietin is produced at a constant rate by the liver and kidney and is
      removed from the circulation upon binding and subsequent uptake via the Tpo
      receptor, c-Mpl, expressed by platelets and mega-karyocytes. Apart from uptake,
      this study shows that platelets can also function as a storage pool for Tpo. Upon
      stimulation with various platelet agonists, full-length biologically active Tpo
      was released by platelets. Platelet fractionation experiments indicated that this
      Tpo most likely is contained in the granules. When platelets were preincubated
      with Tpo-peptide mimetic or truncated Tpo prior to maximal activation, a three-
      to fivefold increment in Tpo release was seen. whereas, the release of other
      granule proteins such as vWF-propeptide or serotonin remained unchanged.
      Therefore, the Mpl agonists might compete with Mpl-bound Tpo, thereby releasing
      Tpo into the platelet supernatant. Intravascular release of Tpo by platelets
      might occur in patients with massive platelet activation, as occurs in patients
      with disseminated intravascular coagulation. The Tpo concentration in these
      patients is elevated (p <0.01) and correlates with markers for thrombin
      generation, TAT complexes and F1+2(r(p)= 0.8 and 0.9; p <0.01). This suggests
      that the increment in Tpo concentration was attributed to Tpo release by
      activated platelets in vivo, which might be instrumental in subsequent
      stimulation of thrombocytopoiesis.

PMID- 10896251
TI  - Hereditary thrombocytopenia due to reduced platelet production--report on two
      families and mutational screening of the thrombopoietin receptor gene (c-mpl).
AB  - Hereditary thrombocytopenias represent heterogeneous clinical and genetic
      syndromes. They include a consistent group of families which are considered as a
      separate clinical entity, characterized by autosomal dominant transmission,
      incomplete penetrance in females, chronic thrombocytopenia with early age of
      onset and frequently increased platelet volume, without any other hematologic
      abnormality. The molecular defect in these families is still unknown. We describe
      2 families in 3 generations (10 patients), and report the first study of the
      TPO/c-mpl system in autosomal dominant thrombocytopenia. We performed mutational
      screening of c-mpl coding, flanking introns and promoter regions in 2 probands
      from the two families by DNA sequencing. The results do not provide evidence of c
      mpl sequence alterations in either of the 2 families investigated. Moreover, the
      normal TPO serum levels detected in 5 patients from each family leads us to
      exclude the possibility of a defect in TPO production in our families. Finally,
      the involvement of both c-mpl and TPO genes in the pathogenesis of
      thrombocytopenia in these two families was excluded by negative results of
      linkage analysis.

PMID- 10896252
TI  - Heparin induces synthesis and secretion of tissue factor pathway inhibitor from
      endothelial cells in vitro.
AB  - TFPI is a potent inhibitor of the extrinsic coagulation system constitutively
      synthesized by endothelial cells. A major portion of intravascular TFPI is stored
      associated with endothelial cells. and administration of unfractionated heparin
      (UFH) in vivo causes a prompt mobilization of TFPI into the circulation. The
      present study was conducted to investigate how UFH affected the synthesis,
      secretion and anticoagulant potency of TFPI in endothelial cells in vitro. A
      spontaneously transformed immortal endothelial cell line was used (ECV304).
      Stimulation of ECV304 cells with UFH caused a prompt dose-dependent (0-5 IU
      UFH/ml) release of TFPI to the medium accompanied by no change of TFPI at the
      surface membrane assessed by immunocytochemical methods. Northern blot analysis
      revealed two mRNA transcripts for TFPI with a molecular size of 1.4 kb and 4.4
      kb, respectively. Stimulation of ECV304 cells for 24 hrs with various
      concentrations of UFH caused a dose-dependent increase of TFPI in the medium (6.2
      29.6 ng/10(6) cells within the concentration range 0-10 IU/ml). A similar dose
      dependent increase in the expression of both TFPI mRNA species was observed. Long
      term incubation of ECV304 cells with 5.0 IU/ml UFH caused a 5-10 fold increase in
      the TFPI concentration accumulated in the medium over 48 hrs. The increased TFPI
      mRNA expression induced by UFH appeared already after 10 min, peaked after 2-4
      hrs, remained augmented throughout the entire period of UFH exposure, and
      preceded the synthesis-dependent increase in TFPI release by 2-4 hrs. The
      procoagulant activity of the cells was downregulated by 36% and the contribution
      of TFPI to the anticoagulant potency of ECV304 cells was moderately increased
      after 24 hrs heparin stimulation. It is suggested that these mechanisms are of
      major importance for the anticoagulant function of heparins.

PMID- 10896253
TI  - Reduced expression of endothelial cell markers after long-term transdermal
      hormone replacement therapy in women with coronary artery disease.
AB  - The effects of 12 months hormone replacement therapy (HRT) on biochemical markers
      associated with endothelial function were studied in 98 postmenopausal women with
      CAD, who were randomized to transdermal HRT or a control group. A significant
      reduction in the levels of von Willebrand factor in the HRT-group compared to
      controls was seen after 3 months, maintained after 12 months (p <0.001).
      Significant reduction in the HRT-group compared to controls was also seen in VCAM
      1 after 3 months, sustained after 12 months (p = 0.013 and p = 0.045,
      respectively), and E-selectin was reduced by about 20% after 3 months on HRT, the
      reduction being statistically significant after 12 months (p <0.001).
      Significantly reduced levels of ICAM-1 were also seen after 12 months (p =
      0.048). No effects could be observed on tPA-antigen or thrombomodulin. The
      reduction in procoagulant and proinflammatory markers of endothelial function
      after long-term transdermal HRT could indicate a beneficial effect on the
      endothelium and thus a potentially modulating effect on the progression of
      atherosclerosis in women with CAD.

PMID- 10896254
TI  - Expression of vascular endothelial growth factor in human umbilical vein
      endothelial cells stimulated with interleukin-1alpha--an autocrine regulation of
      angiogenesis and inflammatory reactions.
AB  - Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial
      cells. We studied the production of VEGF by human umbilical vein endothelial
      cells (HUVEC) and smooth muscle cells (SMC) in response to the stimulation with
      interleukin-1alpha (IL-1alpha). HUVEC expressed VEGF mRNA in response to IL
      1alpha in dose- and time-dependent manners. In HUVEC VEGF protein was detected
      only in cell lysates whereas in SMC most of the VEGF protein was detected in the
      conditioned medium. Immunofluorescent staining also confirmed the cell-associated
      VEGF in HUVEC. IL-1alpha also induced the expression of mRNA for IL-1alpha itself
      in HUVEC. Cycloheximide treatment of HUVEC slightly inhibited the IL-1alpha
      induced expression of VEGF mRNA, and IL-1alpha may mediate, at least in part,
      VEGF expression in response to IL-1alpha. The growth of HUVEC stimulated with IL
      1alpha was inhibited by a neutralizing antibody against VEGF. We conclude that IL
      1alpha and VEGF may play an important role in autocrine growth regulation of
      HUVEC.

PMID- 10896255
TI  - CD9 gene deficiency does not affect smooth muscle cell migration and neointima
      formation after vascular injury in mice.
AB  - The hypothesis that CD9, a member of the tetraspanin family, plays a role in
      smooth muscle cell (SMC) migration was tested with the use of a vascular injury
      model in wild-type (CD9+/+) and CD9-deficient (CD9-/-) mice. Neointima formation
      3 weeks after electric injury of the femoral artery was not significantly
      different in CD9+/+ and CD9-/- mice (area of 0.019 +/- 0.0034 mm2 versus 0.013 +/
      0.0036 mm2; mean +/- SEM, n = 6). The medial areas were also comparable,
      resulting in intima/media ratio's of 1.3 +/- 0.15 and 0.90 +/- 0.22,
      respectively. Nuclear cell counts in cross-sectional areas of the injured region
      were comparable in media (33 +/- 5 versus 27 +/- 2) and neointima (135 +/- 16
      versus 97 +/- 17) of CD9+/+ and CD9-/- arteries. Immunocytochemical analysis
      revealed expression of CD9 in the endothelium, by SMC in the media and by some
      fibroblasts in the adventitia of non-injured femoral arteries. Three weeks after
      injury, there appeared to be a gradient of increased CD9 expression from the
      adventitia to the neointima, in which SMC are abundantly present. Immunogold
      labeling and electron microscopy with non-injured femoral arteries of CD9+/+ mice
      confirmed the presence of CD9 at the surface of adventitial fibroblasts and in
      SMC or pericytes, as well as in the endothelium. Thus, in this model CD9 is
      highly expressed by migrating SMC, but deficiency of CD9 does not affect SMC
      migration or neointima formation after perivascular injury.

PMID- 10896256
TI  - Should superficial vein thrombosis of the proximal greater saphenous vein be
      objectively evaluated in emergency wards?

PMID- 10896257
TI  - In the presence of other inherited or acquired high-risk situations, the FV
      Cambridge mutation may be an additional thrombophilic risk factor, through its
      effect on APC sensitivity.

PMID- 10896258
TI  - High frequency of factor V Leiden mutation in Parsis--a highly endogamous
      population in India.

PMID- 10896259
TI  - Massive skin necrosis associated to the prothrombin gene G20210A mutation.

PMID- 10896260
TI  - A new dilution for the modified APTT-based assay for activated protein C
      resistance: improvement of the reliability in patients with a lupus
      anticoagulant.

PMID- 10896261
TI  - Determination of total plasma homocysteine: comparison of a new enzyme
      immunoassay and a HPLC method.

PMID- 10896262
TI  - Operating characteristics of automated latex immunoassay fibrin D-dimer tests in
      the diagnosis of angiographically-defined acute pulmonary embolism.

PMID- 10896263
TI  - Impact of our understanding of the genetic aetiology of epilepsy.
AB  - A genetic contribution to aetiology is estimated to be present in up to 40% of
      patients with epilepsy. It is useful to categorise genetic epilepsies according
      to the mechanisms of inheritance into Mendelian disorders, non-mendelian or
      'complex' disorders, and chromosomal disorders. Over 200 Mendelian diseases
      include epilepsy as part of the phenotype, and the genes for a number of these
      have been identified recently. These include autosomal recessive progressive
      myoclonic epilepsies such as Unverricht-Lundborg disease, Lafora disease and the
      neuronal ceroid lipofuscinoses, and three autosomal dominant idiopathic
      epilepsies. The last named have been shown to arise from mutations in ion channel
      genes. Autosomal dominant nocturnal frontal lobe epilepsy is caused by mutations
      in CHRNA4, benign familial neonatal convulsions by mutations in KCNQ2 and KCNQ3,
      and generalised epilepsy with febrile seizures plus by mutations in SCN1B.
      'Complex', familial epilepsies are more difficult to analyse, but evidence has
      been obtained for loci predisposing to juvenile myoclonic epilepsy on chromosome
      6p and 15q. Lastly, the genes underlying several spike-wave epilepsies in mice
      have been cloned, and three of these encode sub-units of voltage-gated calcium
      channels.

PMID- 10896264
TI  - Assessing vestibular function: which tests, when?
AB  - Vertigo and dizziness are common complaints encountered in clinical practice. The
      patient's history and a thorough otoneurological evaluation are essential for
      identifying the specific pathology behind the patient's complaints. If the
      patient reports an illusion of movement (vertigo), this most likely indicates an
      imbalance within the vestibular system. A sensation of rotatory movement together
      with a spontaneous nystagmus suggests a lesion involving the semicircular canals,
      while an illusion of linear movement indicates a disturbance of the otoliths.
      Nystagmus of central origin or caused by a peripheral vestibular lesion can
      usually be distinguished by other features in the history or on clinical
      examination. While peripheral vestibular lesions usually lead to a mixed
      horizontal-torsional or vertical-torsional nystagmus, a pure vertical or pure
      torsional nystagmus is always caused by a central lesion. With simple bedside
      tests such as head-shaking nystagmus and rapid head impulses deficits in
      labyrinthine function can clearly be detected. For a more thorough investigation
      of vestibular function at the level of individual semicircular canals and the
      otoliths, modern techniques are now available such as three-dimensional eye
      movement vector analysis for the evaluation of individual semicircular canal
      function, measurement of the subjective visual vertical for utricular, and click
      evoked myogenic potentials for saccular testing.

PMID- 10896265
TI  - Predominant arm weakness in acute idiopathic polyneuritis: a distinct regional
      variant.
AB  - Acute idiopathic polyneuritis is a heterogeneous disorder with a number of
      clearly established variants. We describe four patients who present with an acute
      neuropathy predominantly affecting the arms which we believe should be considered
      as a distinct variant of acute polyneuritis. In two cases a primary demyelinating
      process affecting both motor and sensory nerves is suggested whereas in the other
      two the features were of a pure motor axonal degeneration. The relationship
      between these neuropathies, other variants of acute idiopathic polyneuritis and
      multifocal motor neuropathy is considered.

PMID- 10896266
TI  - Typical Friedreich's ataxia without GAA expansions and GAA expansion without
      typical Friedreich's ataxia.
AB  - We clinically assessed and performed polymerase chain reaction analysis for the
      GAA trinucleotide repeat expansion in 103 patients from 73 families in Ireland,
      with a prior clinical diagnosis of Friedreich's ataxia (FA) or an unclassified
      progressive ataxic syndrome. The patients were classified as "typical" or
      "atypical" FA according to Harding's mandatory clinical diagnostic criteria. All
      patients underwent blood glucose analysis, and electrocardiography and
      echocardiography was performed in 99 and 101 patients, respectively. Mutation
      screening for expanded CAG trinucleotide repeats, associated with spinocerebellar
      ataxia (SCA) 1, 2, 3 and 6 was performed in 86 patients overall, including all
      GAA negative patients. Forty-nine of 56 typical patients and 13 of 47 atypical
      patients were either homozygous or heterozygous for the GAA expansion. Seven
      patients with a typical FA phenotype were negative for the GAA expansion.
      Although one of these patients had vitamin E deficiency, and two had raised alpha
      fetoprotein levels, three other GAA negative patients with a typical FA phenotype
      had no other identifiable cause for their ataxia, once again raising the
      possibility of locus heterogeneity in FA. It is also possible that these patients
      have two point mutations in the X25 gene, or that they have another ataxic
      syndrome mimicking the FA phenotype. Two families who were homozygous for the GAA
      expansion exhibited intrafamilial phenotypic variability. Only one GAA negative
      patient had the SCA 3 mutation, and this was the only patient in the study with a
      possible autosomal dominant inheritance pattern. In the homozygous GAA population
      typical patients had significantly more repeats on the smaller allele than
      atypical patients, and there was an inverse relationship between the number of
      repeats on the smaller allele and the age at presentation. There was also an
      inverse relationship between the repeat size on both the larger and the smaller
      of the two alleles and the age at becoming wheelchair bound. There was no
      significant relationship between repeat size and the other indices of disease
      severity, including the presence or absence of diabetes or cardiomyopathy. This
      is the first large study of an Irish population with progressive ataxia that has
      shown a similar phenotype/genotype relationship to studies of FA in other
      European and non-European populations. The relatively low sensitivity and
      specificity of Harding's clinical diagnostic criteria must be appreciated when
      clinically assessing patients with a progressive ataxic syndrome. Although
      molecular genetic analysis now plays an essential role in diagnosis and
      classification, patients with a typical FA phenotype without any identifiable
      cause for their ataxia exist.

PMID- 10896267
TI  - Visual event-related potentials in progressive supranuclear palsy, corticobasal
      degeneration, striatonigral degeneration, and Parkinson's disease.
AB  - To determine whether there are characteristic changes in event-related potentials
      (ERPs) in parkinsonian syndromes we studied 8 patients with progressive
      supranuclear palsy (PSP), 10 patients with corticobasal degeneration (CBD), 9
      patients with striatonigral degeneration (SND), and 16 patients with idiopathic
      Parkinson's disease (PD) with a mean duration of illness shorter than 5 years in
      each group. A visual oddball paradigm was employed to elicit P300. P300 to the
      rare target and rare nontarget stimuli and reaction time (RT) to rare target
      stimuli in each group were compared with those in the corresponding age-matched
      normal control group and to each other after age correction. The correlation of
      P300 and RT to motor disability score was also studied. In PSP P300 amplitude was
      markedly reduced while in CBD P300 latency was prolonged. P300 amplitude to rare
      nontargets in SND and PD was attenuated. The mean RT in the PSP and the CBD group
      was significantly longer than in the other two groups. The mean RT in PD and P300
      amplitude to rare nontargets in both CBD and PD showed significant correlation
      with the severity of motor disability. Simultaneous measurement of P300 and RT
      may yield useful supplementary information in facilitating diagnosis of
      parkinsonian syndromes in addition to clinical criteria.

PMID- 10896268
TI  - Familial Creutzfeldt-Jakob disease in a patient carrying both a presenilin 1
      missense substitution and a prion protein gene insertion.
AB  - We describe a patient who was clinically diagnosed with familial early-onset
      Alzheimer disease (AD) carrying both the E318G substitution in presenilin 1
      (PSEN1) and an insertion of 7 octapeptide coding repeats in the prion protein
      gene (PRNP). Neuropathological examination revealed elongated cerebellar prion
      protein deposits in the absence of AD pathology. Further analysis of other family
      members showed that the Creutzfeldt-Jakob disease phenotype in this family was
      caused solely by the PRNP insertion. This observation is consistent with our
      previous finding that PSEN1 E318G is not causally related to AD.

PMID- 10896270
TI  - Guidelines for autologous blood and marrow stem cell transplantation in multiple
      sclerosis: a consensus report written on behalf of the European Group for Blood
      and Marrow Transplantation and the European Charcot Foundation. BMT-MS Study
      Group.
AB  - Recent reports suggest the possible beneficial effects of haemopoietic stem cell
      transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS).
      The definition of the risk/benefit ratio for such a treatment is perceived as a
      major issue for the neurological community worldwide. The First Consensus
      Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was
      held in Milan, Italy on 21 February 1998. Participants from 16 European, North
      American, and South American countries discussed the guidelines for performing
      HSCT in MS. This conference was organized in order to: (a) define criteria for
      patient selection; (b) define transplantation procedures to maximize efficacy of
      the treatment and minimize its toxicity; (c) standardize patient outcome
      evaluation; and (d) establish an international working group to evaluate the
      efficacy and safety of HSCT in MS and to study the immunological changes related
      to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a)
      the preparation and distribution of a consensus report on HSCT in MS and (b) the
      design of an open trial for an initial assessment of the safety and efficacy of
      HSCT in MS. The consensus reached during the meeting and the design of the
      clinical trial are summarized in this contribution.

PMID- 10896269
TI  - Muscle autoantibodies in subgroups of myasthenia gravis patients.
AB  - Myasthenia gravis (MG) is caused by autoantibodies to the acetylcholine receptor
      (AChR), but several other muscle autoantibodies have also been identified in
      patient sera. We studied muscle autoantibodies against AChR, striated muscle
      tissue sections (SH), titin, citric acid antigen (CA), and ryanodine receptor
      (RyR) in sera from 146 consecutive MG patients to evaluate whether a single test
      or several tests together can predict a thymoma. The MG patients were divided
      into five subgroups; ocular MG, early-onset MG (< 50 years), late-onset MG (> 50
      years), MG with thymoma, and AChR antibody negative MG. AChR, SH, titin, CA, and
      RyR antibodies were detected in 85%, 34%, 34%, 25%, and 14% of the MG patients,
      respectively. For thymoma MG, AChR, SH, titin, CA, and RyR antibodies were
      detected in 100%, 75%, 95%, 70%, and 70% respectively. SH, titin, CA, RyR
      antibodies, and computed tomography of the anterior mediastinum have similar
      sensitivity for thymoma MG. The specificity of RyR, titin, CA, and SH antibodies
      for thymoma was 70%, 39%, 38%, and 31%, respectively, which is significantly
      higher for RyR antibodies than for the others. No single muscle antibody assay
      can predict a thymoma, and a combination of several antibody assays is preferred,
      although RyR antibody testing alone showed 70% sensitivity and specificity for
      thymoma MG. SH and CA antibodies provided only little additional information.

PMID- 10896271
TI  - Lower altitudinal bilateral hemianopsia in a patient with moyamoya disease.

PMID- 10896272
TI  - Is the optic-spinal form of multiple sclerosis comparable to typical multiple
      sclerosis?

PMID- 10896273
TI  - Motor neuron loss in a patient with spinocerebellar ataxia type 6: chance co
      occurrence or causally related?

PMID- 10896274
TI  - Repetitive cerebral bleeding in an adult with Klippel-Trenaunay syndrome.

PMID- 10896275
TI  - Progressive chorea and amyotrophy without acanthocytes: a new case of Fotopoulos
      syndrome?

PMID- 10896276
TI  - Striatonigral degeneration with motor neuron disease.

PMID- 10896277
TI  - Harvey William Cushing (1869-1939).

PMID- 10896278
TI  - L-glutamate receptor identified as taste receptor of umami.

PMID- 10896279
TI  - Mutations affecting the beta-beta homomeric interaction in propionic acidaemia:
      an approach to the determination of the beta-propionyl-CoA carboxylase functional
      domains.

PMID- 10896280
TI  - Oral lysine feeding in gyrate atrophy with hyperornithinaemia--a pilot study.

PMID- 10896281
TI  - Two novel mutations (E86A, R113W) in argininosuccinate lyase deficiency and
      evidence for highly variable splicing of the human argininosuccinate lyase gene.

PMID- 10896282
TI  - Measurement of neurotransmitter metabolites in the cerebrospinal fluid of
      phenylketonuric patients under dietary treatment.

PMID- 10896283
TI  - Derangement of the dopaminergic system in phenylketonuria: study of the event
      related potential (P300).

PMID- 10896284
TI  - The influence of L-dopa on methylation capacity in aromatic L-amino acid
      decarboxylase deficiency: biochemical findings in two patients.

PMID- 10896286
TI  - Deprenyl in the treatment of patients with tetrahydrobiopterin deficiencies.

PMID- 10896285
TI  - Pathobiochemical implications of hyperdopaminuria in patients with aromatic L
      amino acid decarboxylase deficiency.

PMID- 10896287
TI  - Genotype-phenotype correlation in dihydropteridine reductase deficiency.

PMID- 10896288
TI  - Osteoporosis in late-diagnosed adult homocystinuric patients.

PMID- 10896289
TI  - 3-Methylglutaconyl-CoA hydratase deficiency: a new patient with speech
      retardation as the leading sign.

PMID- 10896290
TI  - Antenatal expression of multiple acyl-CoA dehydrogenase deficiency.

PMID- 10896291
TI  - Oxidative abnormalities in Menkes disease.

PMID- 10896292
TI  - The diagnosis of carnitine palmitoyltransferase II deficiency is now possible in
      small skeletal muscle biopsies.

PMID- 10896293
TI  - Methylmalonic acid induces excitotoxic neuronal damage in vitro.

PMID- 10896294
TI  - Evaluation of trigger factors of acute encephalopathy in glutaric aciduria type
      I: fever and tumour necrosis factor-alpha.

PMID- 10896295
TI  - Mevalonic aciduria in 12 unrelated patients with hyperimmunoglobulinaemia D and
      periodic fever syndrome.

PMID- 10896296
TI  - Molecular basis of classical mevalonic aciduria and the hyperimmunoglobulinaemia
      D and periodic fever syndrome: high frequency of 3 mutations in the mevalonate
      kinase gene.

PMID- 10896297
TI  - Abnormalities in succinylpurines in fumarase deficiency: possible role in
      pathogenesis of CNS impairment.

PMID- 10896298
TI  - Upregulation of respiratory chain enzymes in guanidinoacetate methyltransferase
      deficiency.

PMID- 10896299
TI  - Biochemical and molecular studies in mild flavin monooxygenase 3 deficiency.

PMID- 10896300
TI  - UDPgalactose epimerase in lens and fibroblasts: activity expression in patients
      with cataracts and mental retardation.

PMID- 10896301
TI  - Haemostatic abnormalities and lupus anticoagulant activity in patients with
      Gaucher disease type I.

PMID- 10896302
TI  - Carbohydrate-deficient glycoprotein syndromes: the Italian experience.

PMID- 10896303
TI  - Carbohydrate-deficient glycoprotein syndrome: beyond the screen.

PMID- 10896304
TI  - Transferrin protein variant mimicking carbohydrate-deficient glycoprotein
      syndrome in trisomy 7 mosaicism.

PMID- 10896305
TI  - Defects in the synthesis of cysteinyl leukotrienes: a new group of inborn errors
      of metabolism.

PMID- 10896306
TI  - Smith-Lemli-Opitz syndrome: molecular-genetic analysis of ten families.

PMID- 10896307
TI  - Serum lipids and apolipoproteins in children with the Smith-Lemli-Opitz syndrome.

PMID- 10896308
TI  - Perturbation of protein kinase C subtype activation in X-ALD fibroblasts:
      possible involvement of protein kinase C in the pathogenesis of
      adrenoleukodystrophy.

PMID- 10896309
TI  - Phytanic acid alpha-oxidation in man: identification of 2-hydroxyphytanoyl-CoA
      lyase, a peroxisomal enzyme with normal activity in Zellweger syndrome.

PMID- 10896310
TI  - Characteristic urine organic acid profile in peroxisomal biogenesis disorders.

PMID- 10896311
TI  - Analysis of plasmenylethanolamines using electrospray tandem mass spectrometry
      and its application in screening for peroxisomal disorders.

PMID- 10896312
TI  - The application of HPLC/ESI tandem mass spectrometry on urine-soaked filter-paper
      strips for the screening of disorders of purine and pyrimidine metabolism.

PMID- 10896313
TI  - Structure-based design of potent CDK1 inhibitors derived from olomoucine.
AB  - Cyclin-dependent kinase 1 (CDK1), an enzyme participating in the regulation of
      the cell cycle, constitutes a possible target in the search for new antitumor
      agents. Starting from the purine derivative olomoucine and following a structure
      based approach, potent inhibitors of this enzyme were rapidly identified. The
      molecular modeling aspects of this work are described.

PMID- 10896314
TI  - Computer based screening of compound databases: 1. Preselection of benzamidine
      based thrombin inhibitors.
AB  - We present a computational protocol which uses the known three-dimensional
      structure of a target enzyme to identify possible ligands from databases of
      compounds with low molecular weight. This is accomplished by first mapping the
      essential interactions in the binding site with the program GRID. The resulting
      regions of favorable interaction between target and ligand are translated into a
      database query, and with UNITY a flexible 3D database search is performed. The
      feasibility of this approach is calibrated with thrombin as the target. Our
      results show that the resulting hit lists are enriched with thrombin inhibitors
      compared to the total database.

PMID- 10896315
TI  - Pharmacophore modelling of structurally unusual diltiazem mimics at L-type
      calcium channels.
AB  - The purpose of this theoretical study was to investigate the molecular features
      of some structurally unusual calcium antagonists with experimentally proved
      affinity to the diltiazem-binding site at L-type calcium channels. Therefore,
      sterical and electronic characteristics of cis-/trans-diclofurime, the verapamil
      like derivatives McN-5691 and McN-6186 as well as the natural products
      papaverine, laudanosine, antioquine and tetrandrine were compared with the
      pharmacophoric requirements detected for classical diltiazem-like derivatives.
      This yielded a common pharmacophore model for all of these compounds. Based on
      this model, one single negative molecular electrostatic potential induced by the
      free electron pairs of the oxime oxygen of trans-diclofurime was detected that
      might be responsible for the stronger effects compared to the cis isomer.
      Furthermore, the dual diltiazem- and verapamil-like features of McN-5691 (and McN
      6186) as well as the distinct pharmacophoric assignment of the laudanosine
      enantiomers may be interpreted on a molecular level. Finally, the crucial partial
      structure of the bis-benzylisoquinoline derivatives antioquine and tetrandrine
      being responsible for the calcium antagonistic effects could be revealed by
      superposition on the most active benzothiazepinone derivative 8-methoxydiltiazem.
      The results obtained for these unusual diltiazem mimics are discussed taking into
      consideration earlier findings for classical diltiazem-like derivatives.

PMID- 10896316
TI  - Evaluation of docking/scoring approaches: a comparative study based on MMP3
      inhibitors.
AB  - An increasing number of docking/scoring programs are available that use different
      sampling and scoring algorithms. A reliable scoring function is the crucial
      element of such approaches. Comparative studies are needed to evaluate their
      current capabilities. DOCK4 with force field and PMF scoring as well as FlexX
      were used to evaluate the predictive power of these docking/scoring approaches to
      identify the correct binding mode of 61 MMP-3 inhibitors in a crystal structure
      of stromelysin and also to rank them according to their different binding
      affinities. It was found that DOCK4/PMF scoring performs significantly better
      than FlexX and DOCK4/FF in both ranking ligands and predicting their binding
      modes. Most notably, DOCK4/PMF was the only scoring/docking approach that found a
      significant correlation between binding affinity and predicted score of the
      docked inhibitors. However, comparing only those cases where the correct binding
      mode was identified (scoring highest among sampled poses), FlexX showed the best
      'fine tuning' (lowest rmsd) in predicted binding modes. The results suggest that
      not so much the sampling procedure but rather the scoring function is the crucial
      element of a docking program.

PMID- 10896317
TI  - A genetic algorithm for the automated generation of small organic molecules: drug
      design using an evolutionary algorithm.
AB  - Rational drug design involves finding solutions to large combinatorial problems
      for which an exhaustive search is impractical. Genetic algorithms provide a novel
      tool for the investigation of such problems. These are a class of algorithms that
      mimic some of the major characteristics of Darwinian evolution. LEA has been
      designed in order to conceive novel small organic molecules which satisfy
      quantitative structure-activity relationship based rules (fitness). The fitness
      consists of a sum of constraints that are range properties. The algorithm takes
      an initial set of fragments and iteratively improves them by means of crossover
      and mutation operators that are related to those involved in Darwinian evolution.
      The basis of the algorithm, its implementation and parameterization, are
      described together with an application in de novo molecular design of new
      retinoids. The results may be promising for chemical synthesis and show that this
      tool may find extensive applications in de novo drug design projects.

PMID- 10896319
TI  - Use of electron-electron repulsion energy as a molecular descriptor in QSAR and
      QSPR studies.
AB  - Electron-electron repulsion energy (<Vee>) is presented as a new molecular
      descriptor to be employed in QSAR and QSPR studies. Here it is shown that this
      electronic energy parameter is connected to molecular quantum similarity measures
      (MQSM), and as a consequence can be considered as a complement to steric and
      electronic parameters in description of molecular properties and biological
      responses of organic compounds. The present strategy considers the molecule as a
      whole, thus there is no need to employ contributions of isolated fragments as in
      many calculations of molecular descriptors, like log P or the Free-Wilson
      analysis. The procedure has been tested in a widespread set of molecules:
      alcohols, alkanamides, indole derivatives and 1-alkylimidazoles. Molecular
      properties, as well as toxicity, are correlated using <Vee> as a parameter, and
      extensions to the method are given for handling difficult systems. In almost all
      studied cases, satisfactory linear relationships were finally obtained.

PMID- 10896318
TI  - Pseudoreceptor model for ryanodine derivatives at calcium release channels.
AB  - This paper describes the generation of a pseudoreceptor model for ryanodine
      receptor (RyR) modulating ryanoids in rabbit skeletal muscle. For this purpose,
      the molecular modelling software PrGen was applied to correlate experimentally
      determined and calculated free energies of binding for a set of 15 ryanodine
      derivatives. The final model indicates a narrow cleft with hydrogen bond donor
      and acceptor capacities (represented by an Asn) as most crucial for binding the
      pyrrole carboxylate substituent at C3 of ryanodine. In addition, hydrophobic
      residues flank the aromatic pyrrole ring (Tyr, Phe, and Ile). Two of those
      residues (Tyr and Ile) interact with the 2-isopropyl moiety, which seems to
      contribute to binding. Opposite to the pyrrole locus, a second hydrophobic region
      (represented by a Leu) restricts ryanodine derivatives in their longitudinal axis
      and leads to the discrimination of equatorial and axial positioned methyl groups
      and of polar substituents at C9. Finally, a charged glutamate residue generates
      strong hydrogen bonding and electrostatic interactions with the hydroxyl groups
      at C10 and C15. For this binding-site model--composed of six amino acid residues-
      a correlation for the training set ligands of R = 0.99 (Q2 = 0.975) and a root
      mean square (rms) deviation of 0.568 kcal/mol for the prediction of the binding
      energies of four test set ligands was obtained. Based on this pseudoreceptor
      model the putative topology of the real binding site of ryanoids will be
      discussed.

PMID- 10896320
TI  - De novo design of molecular architectures by evolutionary assembly of drug
      derived building blocks.
AB  - An evolutionary algorithm was developed for fragment-based de novo design of
      molecules (TOPAS, TOPology-Assigning System). This stochastic method aims at
      generating a novel molecular structure mimicking a template structure. A set of
      approximately 25,000 fragment structures serves as the building block supply,
      which were obtained by a straightforward fragmentation procedure applied to
      36,000 known drugs. Eleven reaction schemes were implemented for both
      fragmentation and building block assembly. This combination of drug-derived
      building blocks and a restricted set of reaction schemes proved to be a key for
      the automatic development of novel, synthetically tractable structures. In a
      cyclic optimization process, molecular architectures were generated from a parent
      structure by virtual synthesis, and the best structure of a generation was
      selected as the parent for the subsequent TOPAS cycle. Similarity measures were
      used to define 'fitness', based on 2D-structural similarity or topological
      pharmacophore distance between the template molecule and the variants. The
      concept of varying library 'diversity' during a design process was consequently
      implemented by using adaptive variant distributions. The efficiency of the design
      algorithm was demonstrated for the de novo construction of potential thrombin
      inhibitors mimicking peptide and non-peptide template structures.

PMID- 10896322
TI  - Radiotherapy-associated anemia: the scope of the problem.
AB  - The impact of anemia on cancer patients undergoing chemotherapy is well
      established, but only recently has the prevalence of anemia in patients receiving
      radiotherapy received much attention. Many cancer patients present with anemia
      prior to radiotherapy, and even more experience anemia or a worsening of anemia
      at some point during treatment. However, the problem of anemia is often ignored
      because patients may experience only functional anemia, defined as a hemoglobin
      level less than 12 g/dl. Unless physiologic anemia (hemoglobin = 8 g/dl) is
      discovered, efforts to correct anemia are often not made. Because hemoglobin
      levels <12 g/dl seem to be associated with tumor hypoxia and poorer outcomes of
      radiotherapy in a number of patient populations, ignoring even modest anemia can
      result in decreased locoregional control, overall survival, and quality of life
      (QOL). Because increasing hemoglobin levels 1-2 g/dl is usually easily
      accomplished, there exists the potential for improving outcomes by paying greater
      attention to this problem. This article focuses on the prevalence of anemia,
      particularly functional anemia, and discusses the impact of anemia on
      locoregional control, overall survival, and QOL.

PMID- 10896321
TI  - Selectivity analysis of 5-(arylthio)-2,4-diaminoquinazolines as inhibitors of
      Candida albicans dihydrofolate reductase by molecular dynamics simulations.
AB  - A series of 5-(arylthio)-2,4-diaminoquinazolines are known as selective
      inhibitors of dihydrofolate reductase (DHFR) from Candida albicans. We have
      performed docking and molecular dynamics simulations of these inhibitors with C.
      albicans and human DHFR to understand the basis for selectivity of these agents.
      Study was performed on a selected set of 10 compounds with variation in structure
      and activity. Molecular dynamics simulations were performed at 300 K for 45 ps
      with equilibration for 10 ps. Trajectory data was analyzed on the basis of
      hydrogen bond interactions, energy of binding and conformational energy
      difference. The results indicate that hydrogen bonds formed between the compound
      and the active site residues are responsible for inhibition and higher potency.
      The selectivity index, i.e the ratio of I50 against human DHFR to I50 against
      fungal DHFR, is mainly determined by the conformation adapted by the compounds
      within the active site of two enzymes. Since the human DHFR active site is rigid,
      the compound is trapped in a higher energy conformation. This energy difference
      between the two conformations deltaE mainly governs the selectivity against
      fungal DHFR. The information generated from this analysis of potency and
      selectivity should be useful for further work in the area of antifungal research.

PMID- 10896323
TI  - The impact of fatigue on patients with cancer: overview of FATIGUE 1 and 2.
AB  - Fatigue is a complex, multifactorial disorder with physical, mental, and
      psychological dimensions that has been associated with diminished quality of life
      (QOL) in patients with cancer. The prevalence and severity of fatigue, however,
      has only recently been studied systematically. Two national surveys commissioned
      by The Fatigue Coalition, a multidisciplinary group of medical practitioners,
      researchers, and patient advocates, whose mission is to study the importance of
      fatigue for patients with cancer and their caregivers, have assessed the
      prevalence, severity, and QOL consequences of fatigue in patients with cancer.
      The most recent survey, initiated in 1998, sought to confirm and extend
      observations on the prevalence and impact of fatigue in patients with cancer as
      part of an initiative to develop guidelines for the differential diagnosis and
      treatment of fatigue. The FATIGUE 2 study probed the emotional, social, physical,
      and economic impact of fatigue on patients with cancer and their caregivers.
      Patient perceptions of the professional response to cancer-related fatigue were
      also assessed. The key findings of these surveys are reviewed.

PMID- 10896324
TI  - Impact of anemia in patients with head and neck cancer.
AB  - Head and neck squamous cell carcinoma, which is comprised of a heterogeneous
      group of tumors arising from the epithelial lining of the oral cavity, pharynx,
      and larynx, is a locoregional disease. Tumor hypoxia and anemia are known to
      adversely effect the efficacy of radiation therapy, a local treatment modality.
      Therefore, head and neck cancers represent an ideal model for assessing the
      impact of anemia following treatment with radiation therapy. Various treatment
      strategies aimed at increasing tumor oxygenation in head and neck cancer patients
      (including hyperbaric oxygen and hypoxic cell radiosensitizers) have been
      studied. These studies have been fueled by evidence that hypoxia adversely
      effects the radiosensitivity of cells. Although the exact mechanism of action of
      the oxygen effect is not known, in vitro studies with conventional photon
      radiation therapy under normoxic conditions have shown an effectiveness of 2.5
      3.0 times greater than that achieved under anoxic conditions. Recent studies,
      including large retrospective analyses, have demonstrated the dramatic adverse
      impact of anemia upon locoregional tumor control and survival. These studies,
      which have revealed hemoglobin levels as a powerful prognostic factor, provide
      compelling evidence for the value of reversing anemia and hence tumor hypoxia in
      head and neck cancer patients.

PMID- 10896325
TI  - The relationship between anemia and quality of life in cancer patients.
AB  - Anemia is a common occurrence in patients with cancer, and especially in those
      who undergo chemotherapy. Traditionally, significantly decreased hemoglobin
      levels have been considered to be < or = 8 g/dl and have been associated with
      physiologic manifestations. More recent data have shown that milder anemia
      (hemoglobin levels 10-12 g/dl) has functional consequences as well. This article
      reviews several community-based studies that have analyzed changes in hemoglobin
      concentrations, transfusion requirements, and QOL parameters in anemic patients
      with cancer before and after treatment with epoetin alfa. The results of these
      studies have been consistent and show an increase in hemoglobin and a reduction
      in transfusion requirements when compared with baseline. Furthermore, a
      relationship between increasing hemoglobin levels and an improvement in QOL is
      suggested that is independent of tumor response. Additional studies are
      evaluating the optimal hemoglobin levels for the greatest incremental improvement
      in QOL.

PMID- 10896326
TI  - SpinThin, a simple, inexpensive technique for preparation of thin-layer cervical
      cytology from liquid-based specimens: data on 791 cases.
AB  - BACKGROUND: Acceptance of liquid-based fixatives for cervical cytology has been
      limited by the more complex slide-preparation procedures, increased cost, and
      reports that increased sensitivity has been based largely on comparison with
      conventional cytology without histologic correlation. Here the authors describe
      and evaluate a technically simple and relatively inexpensive method (which they
      call SpinThin) for preparing Cytospin (Shandon Inc., Pittsburgh, PA) cervical
      cytology slides from samples in liquid fixative using a modified electric
      toothbrush holder to put the cells in suspension. Results are compared with
      conventional cytology and histologic biopsy. METHODS: A total of 791 cervical
      cytology specimens from 2 patient groups at high risk of uterine cervical
      neoplasia were entered into this study, and a spatula and cytobrush (174
      specimens) or cytobroom (617 specimens) were used to collect conventional smears.
      The collection device with remaining cellular sample was placed in an alcohol
      based fixative solution; the cells were put into suspension by a brief burst of
      vibration using a modified electric toothbrush holder, then cytocentrifuged on a
      slide and stained with the Papanicolaou technique. RESULTS: Specimen adequacy in
      SpinThin slides was better than that of conventional cytology smears. However,
      the prevalence of dysplasia, including atypical squamous cells of undetermined
      significance (ASCUS-D), in conventional smears and SpinThin slides was the same-
      27% and 25%, respectively--and excluding ASCUS-D, it was 20% in both. The
      prevalence of neoplasia (low or high grade squamous intraepithelial lesion, or
      carcinoma) histologically was 31% in the 647 cases biopsied, and agreement with
      histology was similar for SpinThin and conventional smears. CONCLUSIONS: Using a
      simple and relatively inexpensive new technique (Spin-Thin), slides prepared from
      fluid-based cervical cytology specimens obtained with the cytobrush or cytobroom
      correlated very well with the corresponding conventional smears within major
      diagnostic categories, and both correlated well with histology.

PMID- 10896327
TI  - Association between initial diagnostic procedure and hysteroscopy and abnormal
      peritoneal washings in patients with endometrial carcinoma.
AB  - BACKGROUND: Hysteroscopy has been implicated in the finding of positive
      peritoneal washings (PW) in patients with endometrial carcinoma in several case
      reports. The current study was designed to evaluate whether there was an
      increased incidence rate of positive peritoneal washings in patients after
      hysteroscopy compared with patients who did not undergo hysteroscopy. METHODS:
      Two hundred eighty-four women with endometrial carcinoma were treated by
      hysterectomy with intraoperative PW at the Memorial Sloan-Kettering Cancer Center
      between 1995-1998. They were diagnosed by either endometrial biopsy (EMB) or
      dilatation and curretage (D & C) with or without hysteroscopy during the same
      period. RESULTS: Of 173 patients diagnosed by EMB, 16 had abnormal PW (9.2%). Of
      111 patients diagnosed by D & C, 11 had abnormal PW (9.9%). There was no
      significant difference between the two groups (P = 0.85). Of 23 patients who were
      diagnosed by D & C with hysteroscopy, 3 had abnormal PW (13.0%). Of 177 patients
      who did not undergo hysteroscopy, 17 had abnormal PW (9.6%). Of 84 patients for
      whom information regarding hysteroscopy was not available, 7 had abnormal PW
      (8.3%). The incidence rates among the three groups were not significantly
      different (P = 0.79). CONCLUSIONS: The initial diagnostic procedure, including
      hysteroscopy, does not appear to be associated with a high incidence rate of
      abnormal PW in patients with endometrial carcinoma.

PMID- 10896328
TI  - A review of cytologic findings in neuroendocrine carcinomas including carcinoid
      tumors with histologic correlation.
AB  - BACKGROUND: The nosology of neuroendocrine neoplasia has evolved substantially in
      recent years. The aim of this study was to review the authors' institutional
      experience and diagnostic accuracy for cytologic specimens of neuroendocrine
      carcinoma (NEC) and to identify features most suggestive of neuroendocrine
      differentiation. METHODS: The cytologic and histologic findings of 29 archival
      NEC in which cytology preceded biopsy or resection were compared. The study was
      comprised of 6 carcinoid tumors, 3 atypical carcinoid tumors, 17 high grade NEC
      (5 small cell, 9 large cell, and 3 mixed small/large cell), and 3 combined
      NEC/nonneuroendocrine carcinomas. Cytologic material was derived from 21 fine
      needle aspirates (FNA), 6 bronchial brushing/washings, and 2 gastrointestinal
      tract brushings. RESULTS: Of the 29 cases, the correct cytologic diagnosis was
      rendered in 11. Two cases were identified as NEC but were graded incorrectly. The
      remaining 16 cases were interpreted as nonsmall cell carcinoma (8 cases);
      diagnostic or suspicious of carcinoma, not otherwise specified (7 cases); and
      atypical, indeterminate for malignancy (1 case). On review, neuroendocrine
      features were identified in 14 of the latter 16 cases. CONCLUSIONS: The cytologic
      diagnosis of NEC, both high and low grade, can be difficult. Because of acinus
      like formations and columnar cell shapes, low grade NEC may be mistaken for
      adenocarcinoma. Small cell carcinomas, especially in bronchial brush and wash
      preparations, may be difficult to classify beyond malignant. Large cell NEC may
      be confused with nonneuroendocrine carcinomas because of abundant cytoplasm and
      nucleoli. Attention to the presence of loose cell aggregates in a background of
      singly dispersed cells; feathery patterns created by tumor cells clinging to
      capillaries; rosette formations; delicate, granular cytoplasm; inconspicuous
      nucleoli; molding in high grade tumors; and, most important, speckled or dusty
      chromatin patterns are useful in identifying neuroendocrine differentiation in
      cytologic specimens.

PMID- 10896329
TI  - Aspiration biopsy and the clinical management of patients with malignant melanoma
      and palpable regional lymph nodes.
AB  - BACKGROUND: The presence of lymph node metastases in patients with malignant
      melanoma implies a significant decrease in survival. The authors investigated the
      efficacy of fine-needle aspiration biopsy (FNAB) in the diagnosis of metastatic
      malignant melanoma in 115 patients with melanoma and clinically suspicious
      regional lymph nodes. METHODS: One hundred thirty-three FNABs were performed by
      cytopathologists after referral from surgeons or oncologists using a 25-gauge or
      27-gauge needle. RESULTS: The cytologic diagnosis was negative in 35, atypical in
      1, suspicious in 2, and positive for malignant melanoma in 95. Regional lymph
      node dissections were performed in 78 patients. Of these, 70 positive FNABs were
      confirmed with no false-positive results. The atypical FNAB was proven positive
      for malignant melanoma at surgery. Of the two suspicious FNABs, one was confirmed
      as positive and one showed dermatopathic lymphadenopathy. Of the 35 negative FNAB
      specimens, 5 patients underwent surgery; 3 FNABs were found to be negative and 2
      FNABS were falsely negative. Twenty patients with negative aspirates were
      followed clinically for 22-45 months (mean, 32 months); 19 patients had no
      evidence of disease and 1 patient died of disseminated melanoma. CONCLUSIONS:
      FNAB of palpable lymphadenopathy in patients with malignant melanoma can provide
      a rapid and accurate assessment of lymph node status and expedite the therapeutic
      management of these patients.

PMID- 10896330
TI  - The value of fine-needle aspiration biopsy in the differential diagnosis of adult
      myxoid sarcoma.
AB  - BACKGROUND: The usefulness of fine-needle aspiration biopsy (FNAB) for the
      histologic subtyping of specific sarcomas still is somewhat controversial but is
      becoming increasingly popular in the U.S. METHODS: To determine the accuracy and
      usefulness of FNAB in the differential diagnosis of myxoid sarcoma, the authors
      retrospectively reviewed 18 FNAB specimens (16 primary tumors, 1 local
      recurrence, and 1 metastasis) in 18 patients. The study sample included
      myxoid/round cell liposarcoma in six patients, myxofibrosarcoma in six patients,
      myxoid chondrosarcoma in five patients, and myxoid leiomyosarcoma in one patient.
      RESULTS: All but one tumor were recognized correctly as malignant. With regard to
      primary tumors, a specific cytologic diagnosis was rendered in 13 of 16 patients
      (81%). Problematic areas included the diagnosis of high grade myxofibrosarcoma
      with minimal amounts of myxoid stroma, myxoid liposarcoma with a predominant
      round cell component, and the single case of myxoid leiomyosarcoma. CONCLUSIONS:
      FNAB represents a valuable diagnostic tool for the differential diagnosis of
      myxoid sarcoma, especially myxofibrosarcoma, low grade myxoid liposarcoma, and
      myxoid chondrosarcoma. Due to its prognostic and therapeutic significance, the
      presence of a predominant round cell component in myxoid liposarcoma should be
      documented adequately. Other sarcomas (e.g., leiomyosarcoma) rarely may exhibit a
      prominent myxoid stroma and therefore should be considered in the differential
      diagnosis of adult myxoid sarcoma.

PMID- 10896331
TI  - The role of fine-needle aspiration biopsy in the primary diagnosis of mesenchymal
      lesions: a community hospital-based experience.
AB  - BACKGROUND: The objective of this study was to determine the utility of fine
      needle aspiration biopsy (FNAB) in the primary diagnosis of mesenchymal lesions.
      A total of 162 cases with a diagnosis of benign or malignant mesenchymal lesion
      (excluding lipoma) on FNAB were retrieved from the cytopathology archives for the
      years 1990-1997. METHODS: Patients selected for inclusion in this study underwent
      FNAB as the primary diagnostic modality without a previous tissue diagnosis and
      had a subsequent surgical procedure for definitive histologic correlation.
      Seventy-two patients were selected on the basis of the above criteria. RESULTS:
      Cytologic diagnoses were categorized as benign, malignant, or suspicious for
      malignancy. Among the 72 cases selected, 42 (58%) benign, 18 (25%) malignant, and
      12 (16%) suspicious diagnoses were rendered. Of the patients with benign FNAB
      diagnoses, 39 of 42 (93%) had a benign lesion on histologic follow-up, and 3 of
      42 (7%) had a malignancy. Of the patients with malignant FNAB diagnoses, 17 of 18
      (94%) had a malignant lesion and 1 of 17 (6%) proved to be benign. In the subset
      of suspicious lesions, subsequent histology was benign in 5 of 12 (42%) and
      malignant in 7 of 12 (58%). CONCLUSIONS: Based on our study, FNAB has excellent
      accuracy (88%), sensitivity (89%), and specificity (87%) for classifying a
      mesenchymal tumor as benign or malignant. FNAB can be a rapid and effective tool
      for the primary categorization of mesenchymal lesions and provide reliable
      information to the clinician for triage of patients.

PMID- 10896332
TI  - Ultrasound-guided fine-needle aspiration cytology in the early detection of
      melanoma metastases.
AB  - BACKGROUND: The early detection and treatment of tumor recurrences in melanoma
      patients is dependent on reliable, sensitive, and specific techniques to verify
      suspected tumor metastases. As of now, fine-needle aspiration cytology (FNAC) has
      yet to establish itself in the routine follow-up of melanoma patients. METHODS:
      FNAC procedures were performed in melanoma patients with palpable tumors or
      nonpalpable, ultrasonically suspicious lesions. Cytodiagnostic evaluation of fine
      needle samples obtained from suspicious lesions was performed morphologically.
      Findings were validated either by histopathologic diagnosis or prolonged clinical
      follow-up. RESULTS: The cytologic examination of 739 FNACs from 330 melanoma
      patients was conducted within 1 day of sampling. Complications were not observed.
      This study showed a sensitivity of 97.9% and a specificity of 100.0%. Moreover,
      in 158 FNACs derived from lesions with a diameter less than 1 cm a sensitivity of
      94.6% was achieved. Diagnosis of metastatic melanoma with unknown primary tumor
      was established in 20 cases. CONCLUSIONS: FNAC is very reliable for the early
      detection of melanoma metastases. FNAC is a swift method free of complications
      and is able to replace diagnostic surgery completely for nonmalignant lesions in
      a large number of patients. Moreover, FNAC is especially useful in combination
      with ultrasound in melanoma follow-up and can enable diagnosis of lesions smaller
      than 1 cm without impairment of sensitivity or specificity.

PMID- 10896333
TI  - Calretinin staining pattern aids in the differentiation of mesothelioma from
      adenocarcinoma in serous effusions.
AB  - BACKGROUND: The differentiation between malignant mesothelioma and adenocarcinoma
      based on morphology alone can be a diagnostic challenge. The majority of the
      available antibodies recognize molecules expressed by adenocarcinoma whereas to
      the authors' knowledge specific markers for mesothelial cells are lacking.
      Calretinin, a calcium-binding protein, has been reported to be a selective marker
      for mesothelioma and largely is absent from adenocarcinoma on histologic
      material. The results with cytologic preparations have been inconsistent.
      METHODS: To evaluate the specificity of calretinin in differentiating
      mesothelioma from adenocarcinoma in cytologic preparations, 21 paraffin embedded
      cells blocks of serous effusions from 15 patients with metastatic adenocarcinoma
      and 16 cell blocks from 9 patients with malignant mesothelioma were stained with
      a monoclonal antibody against calretinin. The immunoreactivity was evaluated
      blindly by two observers. Positive staining was defined as nuclear and
      cytoplasmic staining with or without intense membranous decoration. The former
      resulted in a characteristic "fried egg" appearance. RESULTS: Calretinin staining
      was positive in all but 2 cases of mesothelioma (14 of 16 cases; 87.5%). The
      latter contained predominantly spindle-shaped neoplastic mesothelial cells in the
      cell block preparations. All adenocarcinoma specimens were classified as negative
      for calretinin staining; 9 (42.9%) lacked any immunoreactivity and 12 (57.1%)
      showed weak, sparse, coarse, granular cytoplasmic staining without nuclear or
      membranous staining. Benign reactive mesothelial cells, when observed in
      association with adenocarcinoma, also showed the characteristic "fried egg"
      appearance. The difference in the staining pattern of calretinin between cells of
      mesothelial origin and adenocarcinoma cells was statistically significant.
      CONCLUSIONS: Calretinin is a useful marker in differentiating mesothelioma of the
      epithelial type from adenocarcinoma in serous effusions. The "fried-egg"
      appearance or cytoplasmic and nuclear staining pattern is characteristic of cells
      of mesothelial origin.

PMID- 10896334
TI  - The historical discovery of macular edema.
AB  - The occurrence of macular edema, or of intraretinal fluid in general, was largely
      unknown prior to the invention of the ophthalmoscope. One of the first reports on
      'Retinitis in Glycosuria', a disease complex, which today would partly be
      described as diabetic maculopathy, was published in 1856 by Jaeger. His
      observations were confirmed less than twenty years later by Nettleship in London,
      and in 1875 Appolinaire Bouchardat from Paris described fluid and lipid
      accumulation in the macula which led--in his words--to a glucose induced
      amblyopia. The first pathophysiological hypotheses of fluid accumulation in the
      posterior pole were then put forward in 1882 by Tartuferi, who thought the edema
      represented swelling of photoreceptor sheaths. In 1896, the Frenchman Nuel coined
      the term 'oedeme maculaire' which he had observed in a retinitis pigmentosa
      patient. However, it was not until the end of the first World War, that the Swiss
      ophthalmologist Alfred Vogt observed macular edema in a variety of other ocular
      conditions such as iridocyclitiOFF macular edema to a macular hole. A quarter of
      a century later Bangerter coined the German term 'Zystoides Makulaodem', and in
      1950, Hruby was the first to draw attention to the development of macular edema
      after cataract extraction. Three years later this was followed by Irvine's
      classical paper on cystoid macular edema after intra- and extracapsular cataract
      extraction which had been complicated by incarceration of the vitreous in the
      anterior segment with consecutive tugging on the macula. A decade later, the
      phenomenon of cystic fluid accumulation in the macula after cataract extraction
      was further characterised by Gass and Norton using fluorescein angiography. The
      ensuing years saw the emergence of new concepts regarding the blood-retinal
      barrier and the paramount role of its dysfunction in the development of macular
      edema.

PMID- 10896335
TI  - Cellular mechanisms of blood-retinal barrier dysfunction in macular edema.
AB  - PURPOSE: To determine the mechanism of blood-retinal barrier (BRB) dysfunction in
      human and experimental specimens using immunocytochemistry. METHODS:
      Extravascular albumin was localized in clinical specimens and retinas from
      transgenic mice that overexpress vascular endothelial growth factor (VEGF) in the
      photoreceptors. Transgenic mouse retinas were also labeled with Griffonia
      simplicifolia isolectin-B4 (GSA), a lectin that binds to endothelial cells.
      RESULTS: The BRB is established by the presence of tight junctions between the
      retinal vascular endothelial (RVE) cells and the RPE cells and by a paucity of
      intraendothelial cell vesicles. When BRB breakdown occurs in human ocular
      disorders such as diabetic retinopathy, retinitis pigmentosa, or cystoid macular
      edema, staining for extravascular albumin reveals leakage through the tight
      junctions, an upregulation of intraendothelial vesicles, and permeation of RVE or
      RPE cells that have undergone degenerative changes. VEGF, in addition to inducing
      neovascularization (NV), promotes vascular leakage. In VEGF transgenic mice, BRB
      failure is confined to the outer retina, the area where NV occurs. GSA binds to
      the luminal and abluminal surfaces of RVE cells in new and established vessels
      and to intraendothelial vesicles and interendothelial cell junctions in areas of
      vascular leakage. CONCLUSION: BRB dysfunction may be mediated by leakage through
      the tight junctions of RVE or RPE cells, by trans-endothelial vesicular
      transport, or by permeation of RVE or RPE cells that have undergone degenerative
      changes. GSA may be a useful marker to assist in recognizing open tight junctions
      and an increase in intraendothelial cell vesicles, which are indicative of BRB
      failure.

PMID- 10896336
TI  - The molecular structure and function of the inner blood-retinal barrier. Penn
      State Retina Research Group.

PMID- 10896337
TI  - Mechanisms of fluid accumulation in retinal edema.
AB  - This paper reviews the anatomic and physiologic conditions which predispose to
      fluid accumulation within the retina. Retinal edema has its inception in disease
      that causes a breakdown of the blood-retinal barrier in retinal capillaries
      and/or the retinal pigment epithelium (RPE). Edema develops not only because
      protein and fluid enter the extracellular space, but because the external
      limiting membrane and the convoluted extracellular pathway within the retina
      limit the clearance of albumin and other large osmotically-active molecules.
      These molecules bind water to cause edema. Recognition of edema clinically is
      complicated by the facts that angiographic markers (fluorescein and ICG) do not
      match albumin in size, and that clinical leakage does not always correlate
      closely with tissue swelling or functional loss. Active water transport across
      the RPE is efficient at removing subretinal water, but the flow resistance of the
      retina limits RPE access to the water of retinal edema. Consideration of the
      pathophysiology of retinal edema may aid in the development of better strategies
      for managing retinal edema.

PMID- 10896338
TI  - Regulators of vascular permeability: potential sites for intervention in the
      treatment of macular edema.
AB  - Rather than being a non-specific reaction to a noxious stimulus, breakdown of the
      capillary blood-retinal barrier causing macular edema appears to be dependent on
      a number of active processes which may be open to pharmacological manipulation.
      Extracellular influences which may affect barrier function include serum and
      neighboring cell types, which act though cytokines, such as vascular endothelial
      growth factor and transforming growth factor-beta, and other factors. A number of
      intracellular pathways acting on the cytoskeleton and components of the
      intercellular junctional complexes have been identified which mediate agonist
      induced leak of the vascular endothelium. The further elucidation of these
      processes may be useful in the development of better treatments for breakdown of
      the inner blood-retinal barrier.

PMID- 10896339
TI  - Inhibition of membrane-bound carbonic anhydrase decreases subretinal pH and
      volume.
AB  - PURPOSE: The lipophilic carbonic anhydrase (CA) inhibitor acetazolamide has been
      shown to enhance subretinal fluid resorption, reduce subretinal pH, and can
      improve cystoid macular edema, but its clinical use is limited by systemic side
      effects. While these are most likely a result of inhibiting intracellular CA
      isoenzymes, retinal pigment epithelial (RPE) transport is thought to be modulated
      via membrane-bound CA. This study investigates whether benzolamide, a hydrophilic
      CA inhibitor that does not readily penetrate cell membranes, is sufficient to
      modulate subretinal volume and pH. METHODS: Volume and pH were assessed in the
      subretinal space (SRS) of the perfused chick retina-RPE-choroid preparation by
      calculating these variables from data obtained with two different double
      barreled, ion-selective electrodes (H+ for pH and the extracellular space marker
      tetramethylammonium (TMA+) for SRS volume). Light induced variations and changes
      in baseline measurements were recorded before and after addition of 10(-4) M
      acetazolamide or benzolamide to the basal perfusion. RESULTS: Basal perfusion
      with either drug induced both an acidification of the SRS by 0.02-0.04 pH units,
      which occurred within 60 s, as well as an increase in the amplitude of the light
      induced alkalinisation of the SRS. TMA+ concentration in the SRS increased
      steadily over a period of several minutes after basal perfusion with either of
      the CA inhibitors, and the calculated SRS volume was reduced by 40% within 8-10
      min. CONCLUSION: The observation that benzolamide had effects equal to
      acetazolamide suggests that inhibition of membrane-bound CA at the basolateral
      membrane of the RPE is sufficient to decrease subretinal pH and volume. This may
      represent a clinically important mechanism for the resorption of sub- and
      intraretinal fluid.

PMID- 10896340
TI  - Macular hole formation in diabetic retinopathy: the role of coexisting macular
      edema.
AB  - The aim of this study was to characterise different etiologies for the
      development of macular holes in diabetic retinopathy. We examined 8 eyes of 8
      patients with known diabetic retinopathy who had developed a macular hole. These
      were classified as follows: related to macular edema (4 eyes), non-related to
      macular edema (2 eyes), intraoperative (1 eye) or postoperative (1 eye) after
      pars plana vitrectomy for proliferative diabetic retinopathy. In three patients
      the macular holes were treated with pars plana vitrectomy and fluid air exchange.
      In diabetic eyes with macular edema, macular holes may develop because of
      intraretinal exudation combined with increased vitreomacular attachments and
      tractions. The mechanism of macular hole formation in diabetic eyes without
      macular edema probably results from the same increased tangential vitreous
      traction which is seen in idiopathic age-related macular holes. Iatrogenically
      induced macular holes during pars plana vitrectomy for proliferative diabetic
      retinopathy may be also due to intraoperative vitreoretinal tugging. Finally,
      macular holes developing after vitrectomy may have an etiology not related to
      vitreous tractions or attachments.

PMID- 10896341
TI  - Macular edema in retinal vein occlusion: up-date from the central retinal vein
      occlusion study.

PMID- 10896342
TI  - Visual prognosis of macular involvement in peripheral retinal vascular
      malformations.
AB  - The visual prognosis in eyes with and without macular pathology, after treatment
      of the primary, peripheral retinal vascular malformation (PRVM) was studied.
      Seventeen patients (16 eyes) underwent treatment of the PRVM with laser/cryopexy.
      In 13/17 eyes (76.4%) associated macular pathology included, macular oedema
      and/or hard exudates (5 eyes), epiretinal membrane (2 eyes), exudative retinal
      detachment (3 eyes), vascular malformation in macula (2 eyes) and macular hole (1
      eye). Initial visual acuity ranged from counting fingers 20/200. After treatment
      of the primary lesion, the visual acuity improved in five eyes, decreased in one
      eye and remained stable in 7 eyes. Of the four eyes without macular involvement,
      the vision improved after treatment in two eyes and remained stable in two eyes.
      We conclude that a variety of macular lesions can reduce central vision in eyes
      with PRVM. After treatment of only the primary lesion, the macular lesions also
      show changes. Visual acuity can improve or remain stable after treatment of the
      primary lesion. Rarely, the vision can decrease.

PMID- 10896343
TI  - The pathogenesis and clinical presentation of macular edema in inflammatory
      diseases.
AB  - Cystoid macular edema (CME) is a classical complication of ocular inflammation.
      This syndrome was already described by Irvine in 1953 but the pathogenesis of
      this condition remains unclear. Cystoid macular edema can result either from a
      rupture of the inner or from the outer blood ocular barrier. Clinical CME that is
      responsible for a low visual acuity must be differentiated from angiographic CME
      that can be present even without any decrease in visual acuity. Fluid
      progressively accumulates into the outer plexiform layer of the retina and pools
      into cystic spaces. Fluid accumulation can now be better seen with optical
      coherence tomography (OCT). In chronic CME fluid accumulation is associated with
      thinning of the retina and fibrosis. At this stage irreversible lesions are
      present and CME does not respond to medical therapies. Inflammatory CME must be
      differentiated from CME resulting from irreversible vascular damage such as in
      diabetic CME or due to vein occlusions. Experimental research on cystoid macular
      edema has been hampered by the lack of animal model: most of laboratory animals
      have no macula, monkeys appear to be highly resistant to macular edema. Five
      major causes have been suspected to be at the origin of CME: (1) photic
      retinopathy, (2) trauma of ocular tissue, (3) secondary irritation of the ciliary
      body, (4) vitreous traction and (5) pharmaceutically induced CME. Clinical
      experience has shown that pseudophakic CME usually responds well to local therapy
      of steroids and non-steroidal antiinflammatory drugs (NSAIDs) and/or in
      association with systemic acetazolamide. Acetazolamide is increasing fluid
      resorption through the retinal pigment epithelium. Postoperative CME rarely needs
      additional posterior subtenon's injections to resolve. But in CME occurring
      secondary to uveitis additional posterior sub-Tenon's steroid injections or
      systemic steroids may be necessary to decrease the constant release of
      inflammatory mediators.

PMID- 10896344
TI  - Cystoid macular edema in a patient with acquired immunodeficiency syndrome and
      past ocular history of cytomegalovirus retinitis after initiation of protease
      inhibitors.
AB  - PURPOSE: To describe a patient with acquired immunodeficiency syndrome (AIDS) who
      presented with cystoid macular edema (CME) which was not associated with active
      cytomegalovirus (CMV) retinitis or AIDS-related microvasculopathy. METHOD: A 32
      year-old man with AIDS and a past ocular history of inactive CMV retinitis was
      placed on protease inhibitors when his CD4+ T lymphocyte counts dropped to 8
      cells/mm3. Three months later, after his CD4+ T lymphocyte counts had increased
      to 196 cells/mm3 he complained of micropsia and metamorphopsia in his right eye
      of 1 week duration. The patient had a complete ocular examination including
      fluorescein angiography (FA). RESULTS: Visual acuity (VA) was 7/10 OD. Fundus
      examination revealed CME and inactive CMV retinitis, and FA demonstrated CME and
      a hot disc. Two transseptal injections of corticosteroids were administered 2
      weeks apart in the right eye as treatment of the CME. The patient reported
      gradual visual improvement and 6 weeks later, his VA was 10/10(-2). CME had
      resolved clinically and angiographically. CONCLUSIONS: CME in our case is
      associated with inactive CMV retinitis and gradually increasing number of CD4+ T
      lymphocytes after initiation of treatment with protease inhibitors. It may be
      amenable to regional administration of corticosteroids without reactivation of
      retinitis.

PMID- 10896346
TI  - Macular edema induced by phacoemulsification.
AB  - PURPOSE: To characterise the association between lens phacoemulsification and the
      development of macular edema. METHODS: We studied 15 patients who underwent lens
      phacoemulsification in our clinic between January and April 1998 performed by the
      same surgeon. Ultrasound power and cumulative time was noted. Follow-up was
      performed at 1 day, 1 week, 1, 3 and 6 months after operation. On each visit
      corneal thickness, best corrected visual acuity, biomicroscopy and fluorescein
      angiography were performed. Patients with systemic diseases and/or retinal
      diseases were not included. RESULTS: Visual acuity was inversely related to the
      amount of energy delivered during phacoemulsification. In patients who had
      received more than 1 Joule of energy, fluorescein angiography revealed a higher
      incidence of blood retinal barrier breakdown. Corneal thickness was not
      correlated with the ultrasound energy used. CONCLUSIONS: Excessive use of power
      during phacoemulsification may hamper the postoperative evolution of cataract
      surgery.

PMID- 10896345
TI  - Is scleral fixation a safe procedure for intraocular lens implantation?
AB  - PURPOSE: No consensus currently exists on the optimal method for intraocular
      (IOL) implantation without capsular support. We evaluated the outcome and
      angiographic findings of eyes that underwent the implantation of scleral fixated
      IOLs. METHODS: Iris and retinal fluorescein angiography were performed in 13 eyes
      that had received posterior chamber IOL implantation with scleral fixation.
      Follow-up examinations also assessed visual acuity (VA), intraocular pressure
      (IOP), IOL decentration and complications related to the procedure. RESULTS: Mean
      visual acuity was 0.29 preoperatively and 0.71 postoperatively after a mean
      follow-up of 14.2 months. A best corrected visual acuity of 0.5 or better was
      obtained in 12 eyes. Iris fluorescein angiography did not show major vascular
      abnormalities. Retinal angiography showed 5 cases of macular edema. In 6 eyes
      light-induced retinal lesions occurred. Cellophane maculopathy was disclosed in 4
      eyes. Macular edema was associated with photic injury in 4 cases and with
      cellophane maculopathy in 2 cases. Mean postoperative visual acuity was 0.6 in
      eyes with macular edema and 0.88 in eyes without (SD 0.18; range 0.5-1.0). Four
      of 5 eyes with macular edema had a postoperative visual acuity of 0.5 or better.
      There was no evidence of persistent IOP elevation or IOL decentration. No serious
      complications were recorded during surgery. CONCLUSIONS: Transscleral fixation of
      posterior chamber IOLs provides adequate visual acuity in most patients. Macular
      edema was frequently associated with the procedure. Although this complication
      was a cause of low visual recovery after implantation, the majority of eyes with
      macular edema achieved a visual acuity of 0.5 or better. Light-induced retinal
      injury was a permanent complication.

PMID- 10896347
TI  - Cyst formation in optic disc pit maculopathy.
AB  - PURPOSE: To evaluate the presence and the evolution of cyst formation in optic
      disc pit maculopathy. METHODS: In this prospective study, 18 cases with optic
      disc pit maculopathy were studied. Five of them showed cyst formation in the
      fovea at the initial examination. The fundus findings were documented with slit
      lamp biomicroscopy, indirect ophthalmoscopy, and stereoscopic photography of the
      posterior pole. All 5 patients were treated with a macular scleral buckle
      procedure. RESULTS: The presence of cysts in the elevated macula depends on the
      grade of the disease. Cyst formation can develop not only in the later stage of
      the disease but also quite early. In all 5 patients cyst formation gradually
      decreased and finally disappeared after the surgical procedure. CONCLUSIONS: Cyst
      formation is an entity which accompanies the macular detachment associated with
      optic disc pit. The development of the cysts has been noticed after the
      establishment of the schisis-like separation and before or in conjunction with
      the formation of a lamellar macular hole which usually accompanies the optic disc
      pit maculopathy.

PMID- 10896348
TI  - Optical coherence tomography (OCT) in macular edema.

PMID- 10896349
TI  - Novel imaging techniques for diabetic macular edema.
AB  - Retinal edema should be defined as any increase of water of the retinal tissue
      resulting in an increase in its volume. It may be of cytotoxic or vasogenic
      origin. Development of vasogenic macular edema is dependent on a series of
      factors such as blood pressure, blood-retinal barrier permeability, retinal cell
      damage, retinal tissue osmotic pressure and retinal tissue compliance. Objective
      measurements of retinal thickness are now possible using the Retinal Thickness
      Analyser. Localised measurements of blood-retinal barrier permeability may also
      be obtained using the Retinal Leakage Analyser, a modified confocal scanning
      laser fluorometer, while obtaining simultaneously angiographic images of the
      choroid and retina. These new imaging techniques show that cytotoxic and
      vasogenic retinal edema may occur independently in the early stages of diabetic
      retinopathy. These findings offer new perspectives for designing novel
      therapeutic strategies.

PMID- 10896350
TI  - Reproducibility of volumetric macular measurements in diabetic patients with the
      Heidelberg Retina Tomograph.
AB  - AIMS: To quantify diabetic macular edema by confocal scanning laser
      ophthalmoscopy and assess its usefulness by determining the reproducibility of
      topographic measurements at the macula. METHODS: The volumes above reference
      plane bound by a 2 mm diameter circle centred on the fovea were measured by two
      observers. The reference plane was adjusted to the lowest point of the height
      variation of the contour line. The reproducibility of this technique was assessed
      in 20 eyes of 20 diabetic patients of which 8 eyes had macular edema. Three HRT
      scans of each eye were obtained. The measurements of volume above reference plane
      of each scan were repeated three times. RESULTS: For all diabetic eyes, the intra
      scan coefficients of variability measured 14.71% to 21.21%, the inter scan
      coefficient of variability was 30.46%. The average standard deviations were 0.053
      mm3 for one examination per scan, 0.047 mm3 for two examinations per scan and
      0.044 mm3 for three examinations per scan. Linear regression demonstrated an
      increase in standard deviation with greater volumetric measurements (p < 0.001).
      We found good correlation (r = 0.959, p < 0.001) and strong agreement between the
      two observer's findings for all 20 eyes. For the 8 eyes with macular edema, the
      coefficients of variability were similar to those calculated for all 20 eyes. The
      average SD for one examination per scan were 0.078 mm3, 0.069 mm3 for two
      examinations per scan and 0.062 mm3 for three examinations per scan. We found
      good correlation (r = 0.945, p < 0.001) and strong agreement between the two
      observer's findings in eyes with edema. CONCLUSION: The reproducibility of this
      technique has been demonstrated in diabetic eyes. This may have useful clinical
      applications for the quantification of diabetic macular edema and monitoring of
      laser therapy.

PMID- 10896351
TI  - Diabetic maculopathy induced by vitreo-macular traction: evaluation by optical
      coherence tomography (OCT).
AB  - AIM: To evaluate the role and efficacy of optical coherence tomography (OCT) in
      the evaluation of diabetic maculopathy induced by vitreo-retinal traction.
      METHODS: 12 patients affected by diabetic maculopathy induced by vitreo-retinal
      traction were examined using biomicroscopy with a three-mirror contact lens,
      fluorescein angiography (FA) and OCT scanning in order to identify the presence
      of a vitreomacular traction. RESULTS: OCT revealed two patterns of maculopathy
      which were characterised by a thickening of the superior profile of the OCT
      tomogram or by the disappearance and inversion of the physiologic foveal
      depression respectively. CONCLUSIONS: OCT may be useful in the characterisation
      and monitoring of diabetic maculopathy induced by vitreo-retinal traction.

PMID- 10896352
TI  - Optical coherence tomography (OCT) in idiopathic polypoidal choroidal
      vasculopathy (IPCV).
AB  - PURPOSE: Idiopathic polypoidal choroidal vasculopathy (IPCV) is a distinct
      clinical entity characterized by an edematous maculopathy and typical choroidal
      vascular change. The purpose of this study is to evaluate the use of optical
      coherence tomography (OCT) for diagnosing of this disease. METHODS: 4 patients
      affected by IPVC (mean age 71-84 years) underwent biomicroscopy with a three
      mirror conctact lens, fluorescein angiography (FA), indocyanine green angiography
      (ICGA) and OCT (Humphrey Zeiss) scan. RESULTS: in all 4 cases OCT tomograms
      acquired at the location of the typical choroidal abnormalities demonstrated by
      ICGA, revealed a characteristic hyper-reflectivity in the choroidal layers.
      CONCLUSION: ICGA is essential to diagnose IPVC, but OCT may be able to identify
      characteristic reflectivity patterns.

PMID- 10896353
TI  - New diagnostic tools for macular edema.

PMID- 10896354
TI  - Treatment of cystoid macular edema with non-steroidal anti-inflammatory drugs and
      corticosteroids.

PMID- 10896355
TI  - The role of carbonic anhydrase inhibitors in the management of macular edema.
AB  - Medical treatment of cystoid macular edema (CME) with carbonic anhydrase
      inhibitors has been known for over a decade. Initial observations were based on
      experimental data which suggested that acetazolamide can increase fluid
      absorption across the retinal pigment epithelium. Carbonic anhydrase inhibitors
      (CAI) have also been shown to have other direct effects both on retinal and
      retinal pigment epithelial cell function by inducing an acidification of the
      subretinal space, a decrease of the standing potential as well as an increase in
      retinal adhesiveness. It is thought that acidification of the subretinal space is
      finally responsible for the increase in fluid resorption from the retina through
      the RPE into the choroid. Several clinical studies have suggested that patients
      with cystoid macular edema due to retinitis pigmentosa and uveitis may react more
      favorably to CAI treatment than other etiologies such as diabetic maculopathy or
      macular edema after retinal vein occlusion. The present working hypothesis is
      that diffuse leakage from the RPE responds more readily to CAI treatment than
      leakage from retinal vessels. This may be due to the modulation of membrane-
      bound CA IV in the RPE which may have lost its polarised distribution in the
      presence of macular edema. A normal clinical starting dose of CAI is 500 mg/day
      which should be continued for at least one month to see an effect. This dose may
      be reduced by the patients over the course of therapy. Metaphylaxis to the drug
      may occur with a rebound of the edema despite continuation of treatment.

PMID- 10896357
TI  - Treatment of uveitic macular edema with acetazolamide.

PMID- 10896356
TI  - Medical treatment of macular edema in patients with uveitis.
AB  - PURPOSE: To determine the efficacy of medical treatment of cystoid macular edema
      (CME) in patients with uveitis. METHODS: Retrospective study of 40 patients (57
      eyes) with uveitis and CME. Inclusion criteria were presence of CME with minimal
      and no macular pathology, or vascular disease which could account for CME.
      Patients who had undergone intraocular surgery or had visual acuity (VA) of > or
      = 20/40 were excluded. The diagnosis of CME was based on clinical and/or
      angiographic findings. Three treatment groups were defined: (1) transseptal
      injection of steroids (n=13 eyes); (2) systemic non steroidal anti-inflammatory
      drugs (NSAIDs) (n=11 eyes); both 1 and 2 (n=33 eyes). RESULTS: Overall, 79% of
      eyes improved 3 or more lines of Snellen VA after treatment: 51% improved 4 or
      more lines. The average number of lines improved was 3.8 for eyes treated with
      transseptal injections of steroids, 2.9 for eyes treated with NSAIDs, and 4 for
      eyes treated with both. For all 3 treatment groups between 60-70% of eyes
      improving 2 or more lines reached best VA only after a minimum of 6 months of
      follow up. CONCLUSIONS: CME, a vision threatening complication of uveitis,
      respond fairly well to medical treatment; however, the best VA is achieved after
      several months. The improvement in VA did not differ markedly among the three
      treatment groups.

PMID- 10896358
TI  - When and how to do a grid laser for diabetic macular edema.
AB  - Macular edema is a common feature of posterior segment diseases. It is an
      expression of abnormal permeability in either retinal vessels (inner blood
      retinal barrier) or in the retinal pigment epithelium (outer blood-retinal
      barrier). It occurs in either a diffuse pattern where the macula appears
      generally thickened or, in more severe cases, as cystoid edema with the typical
      petaloid appearance. Grid laser treatment may be useful to reduce macular edema.
      Spots of 100-250 micrometers in diameter are applied to the whole posterior pole,
      one to two groups apart. The foveal avascular zone remains untouched. In patients
      treated bilaterally, areas temporal and nasal to the macula must be spared to
      prevent the development of deep scotomas. The mechanism yielding positive results
      with the grid technique is still debated. Among the most reliable hypotheses are:
      Proliferation of pigment epithelial cells, followed by and improved efficiency of
      the outer blood-retinal barrier; proliferation of endothelial cells in retinal
      capillaries followed by an improved efficiency of the inner blood-retinal
      barrier; improvement of the retinochoroidal exchanges, and finally, release by
      coagulative necrosis of a factor able to improve the efficiency of the blood
      retinal barriers. Lasers with long wavelengths, such as krypton red and diode,
      are the most appropriate ones to perform grid treatment.

PMID- 10896359
TI  - Grid photocoagulation for focal diabetic macular edema with focal leaks and hard
      exsudates involving the peri-foveolar area.
AB  - This study was conducted to determine whether indirect grid laser therapy is
      effective in reducing focal diabetic macular edema characterised by focal leaks
      and hard exsudates involving the para-foveal area (less than 300 microns from the
      center of the fovea). Since focal coagulation of microaneurysms in such a
      critical location can be deleterious, indirect grid pattern laser treatment may
      be used in such cases.

PMID- 10896360
TI  - Grid laser treatment of macular edema in macular branch retinal vein occlusion.
AB  - AIM: Macular branch retinal vein occlusion (MBRVO) is a subgroup of branch
      retinal vein occlusion in which the occlusion is limited to a small venous vessel
      draining a sector of the macular region. The present study aims to evaluate the
      efficacy of grid laser treatment for macular edema in MBRVO. METHODS: 77 Patients
      with MBRVO of recent onset were prospectively studied during a 24 month period.
      Eyes were randomly assigned to a grid laser treatment group and to a control
      group. Clinical parameters such as visual acuity, presence of macular edema and
      angiographic features were recorded during the follow-up period. RESULTS: Visual
      acuity increased significantly in both groups after 3 months of follow-up
      (p<0.001) and after 1 year of follow-up (p<0.005). No additional improvement was
      noted at the two year control. There was no statistical difference between the
      two groups. CONCLUSIONS: The visual prognosis of MBRVO is not improved after grid
      laser treatment of macular edema. This suggests that sudden ischemic damage to
      central photoreceptors rather than macular edema is the main factor for permanent
      visual acuity reduction.

PMID- 10896361
TI  - The place of vitreoretinal surgery in the treatment of macular oedema.

PMID- 10896362
TI  - Vitrectomy for traction macular edema.
AB  - PURPOSE: Traction macular edema may develop through contraction of macular
      epiretinal membranes (ERM), or due to persistent vitreomacular traction during
      the evolution of vitreomacular traction syndrome (VMS). The purpose of this
      retrospective study was to determine the effect of vitreous surgery and the
      release of the vitreomacular traction or the removal of epiretinal membranes, on
      the evolution of traction induced macular edema. MATERIAL AND METHODS: Fourteen
      eyes from 14 patients presenting with idiopathic or secondary epiretinal
      membranes, and 11 eyes from 10 patients presenting with vitreomacular traction
      syndrome, underwent vitrectomy for reduced vision and cystoid macular edema,
      identified by slit-lamp examination and fluorescein angiography. No coexistent
      ocular conditions that might have caused macular traction were present. History,
      preoperative eye examination, operative findings, postoperative course and final
      examination as well as pre- and postoperative fluorescein angiography were
      reviewed. RESULTS: In the ERM group, cystoid macular edema disappeared in all
      cases during the postoperative period and the mean visual acuity (VA) at the end
      of the follow-up (0.48 +/- 0.23) significantly increased compared to the
      preoperative one (0.29 +/- 0.2) (p=0.004). In the group of patients suffering
      from VMS, the posterior vitreous traction on the macula was released and macular
      edema disappeared in all cases but one. The mean v.a. at the end of the follow-up
      (0.42 +/- 0.24) significantly increased compared to the preoperative one (0.18 +/
      0.1) (p=0.01). Complications included intraoperative small petechias and
      postoperative progressive nuclear sclerosis, retinal detachment and retinal
      pigment epitheliopathy. CONCLUSIONS: Cystoid macular edema may develop secondary
      to vitreomacular traction syndrome or epiretinal membrane contraction. Vitrectomy
      is effective in releasing macular traction which, in turn, may induce a decrease
      of the macular edema with improvement of visual acuity.

PMID- 10896363
TI  - Vitrectomy for macular pucker and vitreomacular traction syndrome.
AB  - During the course of a so-called posterior vitreous detachment, a thin layer of
      the posterior vitreous cortex often remains adherent to the underlying retina.
      Tangential stretch of this vitreous pseudomembrane may cause vitreomacular
      traction syndrome, edema, and macular hole formation. The same process appears to
      underlie the development of true epimacular membranes (idiopathic macular
      pucker). Vitrectomy is generally agreed to be the most appropriate treatment for
      these clinical situations. We evaluated the incidence of vitreomacular adhesion
      and of visual improvement after vitrectomy of eyes with macular pucker (group 1;
      n=60) and vitreomacular traction syndrome (group 2; n=50). Vitreomacular
      attachment was assessed during vitrectomy under the condition of continuous air
      infusion. In the two groups, complete or partial vitreous attachment to the
      macula was observed in 57.4% and 74%, respectively. We conclude that
      vitreomacular adhesion is a common feature of the two clinical situations. Visual
      improvement was achieved in 73% of both groups. High rates of postoperative
      visual acuities of 20/50 or better (60.6% in group-1; 65.7% in group-2 cases)
      occurred only in eyes with preoperative values of 20/100 or better. It is
      reported that the visual outcome of vitreoretinal surgery for the two clinical
      conditions deteriorates with increasing duration after initial manifestation.
      Vitrectomy should not be postponed in patients who complain of disturbing visual
      symptoms such as reduced visual acuity, metamorphopsia and disturbance of
      binocular reading.

PMID- 10896364
TI  - Cystotomy for diabetic cystoid macular edema.
AB  - The purpose of this study was to evaluate the role of vitrectomy with cystotomy
      in the treatment of diabetic cystoid macular edema (CME). Among 22 eyes of 21
      patients with diabetic CME underwent phacoemulsification, intraocular lens
      implantation, pars plana vitrectomy, induction of posterior vitreous detachment,
      and cystotomy or cystectomy. Follow-up ranged from 3 to 29 months. Under
      biomicroscopic examination, Cystoid macular edema was eliminated in 16 of 22 eyes
      during the follow-up period. Ring-shaped residual edema was observed in one eye.
      Corrected visual acuity improved in 7 of 22 eyes by more than one Snellen line (P
      = 0.0391, paired t-test), remained the same in 13 eyes, and decreased by more
      than one line in 2 eyes. This pilot study shows that cystotomy may have a role in
      the treatment of cystoid macular edema in diabetic patients.

PMID- 10896365
TI  - Vitrectomy for macular edema combined with retinal vein occlusion.
AB  - This study was performed in order to evaluate the effect of vitrectomy in eyes
      with retinal vein occlusion associated with macular edema. Twenty-nine years eyes
      (27 patients) with branch retinal vein occlusion (BRVO), and 14 eyes (13
      patients) with central retinal vein occlusion (CRVO) both associated with macular
      edema underwent phacoemulsification, intraocular lens implantation, pars plana
      vitrectomy and peeling of the posterior hyaloid membrane. Follow-up ranged from
      12 to 32 months. Macular edema was reduced, and visual improvement was observed
      (p < 0.0001 in BRVO, p = 0.0257 in CRVO, paired t-test). Visual outcome was
      better in eyes with better visual acuity before surgery. Early vitrectomy may be
      recommended for retinal vein occlusion associated with macular edema.

PMID- 10896367
TI  - It's time to sweat the little things.

PMID- 10896366
TI  - Pars plana vitrectomy in diabetic macular edema.
AB  - PURPOSE: To ascertain the association between the improvement of diabetic macular
      edema and increased visual acuity after pars plana vitrectomy. METHODS: From
      January 1994 to December 1996 we prospectively studied 18 patients (18 eyes, 7
      women and 11 men, mean age 52 years, range 37-68) with type II diabetes and
      clinically significant macular edema. One group was composed of 9 patients
      presenting diffuse macular edema (DME); a second group with 9 patients presented
      cystoid macular edema (CME). All patients underwent pars plana vitrectomy.
      RESULTS: Preoperative Snellen visual acuity was 20/143 in DME and 20/441 in CME.
      In both groups vision increased to 20/136 and 20/205, respectively,
      postoperatively. For the DME this difference was statistically significant
      (p<0.05) at 1 month after the surgery, but vision decreased again after 10 months
      reaching preoperative values. CONCLUSIONS: Our results suggest that pars plana
      vitrectomy for diabetic macular edema may increase visual acuity in diffuse
      macular edema, although this increase is only short lived.

PMID- 10896368
TI  - Trauma- and sepsis-induced hepatic ischemia and reperfusion injury: role of
      angiotensin II.
AB  - HYPOTHESIS: We hypothesized that angiotensin II, a potent vasoconstrictor, is
      involved in the occurrence of hepatic ischemia after burn and sepsis, and that
      administration of angiotensin II antagonist DuP753 would ameliorate this process.
      DESIGN: Randomized animal study. SETTING: University laboratory, investigational
      intensive care unit, University of Texas Medical Branch, Galveston. MATERIALS:
      Female pigs (n = 18, weighing 20-25 kg). INTERVENTIONS: All animals were prepared
      with ultrasonic flow probes 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. Escherichia coli lipopolysaccharide (100
      microg/kg) was intravenously administered at 18 hours postburn DuP753 was
      administered intravenously in a dose of 1 microg/kg to 6 pigs immediately after
      the burn. All animals were studied for 42 hours. MAIN OUTCOME MEASURES: Systemic
      and hepatic hemodynamics were measured and blood samples were drawn for
      determinations of arterial, mixed venous, and portal blood gases at baseline and
      at 14 consecutive time points, starting 1 hour after the burn. RESULTS: Burn
      caused a 4.6-fold increase in hepatic arterial vascular resistance and a 49%
      decrease in hepatic arterial blood flow. Postburn administration of angiotensin
      II receptor blocker DuP753 yielded a significant improvement in the hepatic
      arterial hemodynamics (only 12% increase in hepatic arterial vascular resistance
      and 8% decrease in hepatic arterial blood flow, P<.05 vs nontreated group,
      analysis of variance [ANOVA]). Postlipopolysaccharide hepatic arterial blood flow
      was significantly reduced (12% of baseline, P<.05, ANOVA), in contrast to DuP753
      treated animals (64% of baseline, P<.05 vs nontreated group, ANOVA). Postburn
      blocking of angiotensin II receptors yielded a significant improvement in
      postlipopolysaccharide portal venous blood flow (85% of baseline vs 48% of
      baseline in nontreated animals, P<.05, ANOVA ). Postburn endotoxemia resulted in
      a significant decrease of hepatic oxygen delivery (22% of baseline) and hepatic
      oxygen consumption (30% of baseline), while no marked changes were observed in
      the DuP753-treated group (P<.05 vs nontreated group, ANOVA). CONCLUSIONS:
      Angiotensin II seems to play a pivotal role in burn- and sepsis-induced hepatic
      ischemia and reperfusion injury. Blocking angiotensin II receptors by DuP753
      seems to abrogate this adverse effect of thermal injuries and sepsis on hepatic
      perfusion and oxygenation.

PMID- 10896369
TI  - Wound healing trajectories as predictors of effectiveness of therapeutic agents.
AB  - BACKGROUND: One goal of wound healing research is to discover agents to
      accelerate healing. Regulatory agencies have suggested stringent criteria to
      determine efficacy, that of 100% wound closure. Data analysis at a single point
      such as 100% closure does not provide detailed information about agent
      effectiveness over the entire span of healing. HYPOTHESIS: Wound healing
      trajectories can provide such information and can be used to demonstrate utility
      as alternative end points for wound healing trials. DESIGN: Data from 160
      patients in 11 clinical trials of diabetic foot ulcers conducted at 2 centers
      were evaluated. Wound healing trajectories were constructed for patients whose
      wounds healed (100% closure) and those whose did not (<100% closure) over a 20
      week period. The percentage of patients achieving total healing vs time of
      treatment was plotted and divided into patients receiving a test agent or
      placebo. RESULTS: The healing trajectories were almost identical for patients
      achieving complete healing at the 2 centers, as were the trajectories for
      patients with less than 100% closure. However, the trajectories of patients
      achieving total healing were significantly different from those not achieving
      100% closure. Fifty-two percent of all patients achieved 100% healing by 20
      weeks; 61% of patients receiving an experimental agent had total healing compared
      with 39% of placebo-treated patients. Linear regression suggested that all
      patients would achieve total healing by 37 weeks. CONCLUSIONS: Since wound
      healing trajectories for diabetic foot ulcers treated at 2 centers so closely
      mimic one another, trajectories might be useful efficacy end points, and used to
      compare significant points along a continuum rather than a single static end
      point. Shifting of the wound healing trajectory from an impaired to a more ideal
      course may be considered when determining efficacy of new wound treatments.

PMID- 10896370
TI  - Distal polytetrafluoroethylene bypasses in patients older than 75 years.
AB  - HYPOTHESIS: Polytetrafluoroethylene (PTFE) alone is justified for infrapopliteal
      arterial grafting in elderly patients with critical ischemia of the lower limbs
      who lack a suitable, autogenous saphenous vein. DESIGN: A consecutive sample
      clinical study with a mean follow-up of 16 months. SETTING: The surgical
      department of an academic tertiary care center and an affiliated secondary care
      center. PATIENTS: Thirty-one patients older than 75 years with critical ischemia
      of the lower limbs received 34 PTFE bypass grafts to the infrapopliteal arteries:
      12 patients to the anterior tibial, 8 to the peroneal, 8 to the posterior tibial,
      and 2 to the dorsalis pedis artery. MAIN OUTCOME MEASURES: Cumulative survival,
      primary graft patency, and limb salvage rates expressed by standard life-table
      analysis. RESULTS: Operative mortality rate was 3%. Cumulative survival rate was
      80% at 2 years (SE, 9.2%) and 43% at 3 years (SE, 11.4%). Cumulative primary
      patency rate was 67% at 2 years (SE 9.1%), and 61% at 3 years (SE, 12.7%).
      Cumulative limb salvage rate was 77% at 2 years (SE, 8.7%) and 70% at 3 years
      (SE, 12.8%). CONCLUSION: Polytetrafluoroethylene alone is justified as graft
      material for infrapopliteal bypass grafts in elderly patients with critical
      ischemia of the lower limbs and without a suitable autogenous saphenous vein.

PMID- 10896371
TI  - Computers and virtual reality for surgical education in the 21st century.
AB  - Surgeons must learn to perform operations. The current system of surgical
      resident education is facing many challenges in terms of time efficiency, costs,
      and patient safety. In addition, as new types of operations are developed
      rapidly, practicing surgeons may find a need for more efficient methods of
      surgical skill education. An in-depth examination of the current learning
      environment and the literature of motor skills learning provides insights into
      ways in which surgical skills education can be improved. Computers will certainly
      be a part of this process. Computer-based training in technical skills has the
      potential to solve many of the educational, economic, ethical, and patient safety
      issues related to learning to perform operations. Although full virtual-reality
      systems are still in development, there has been early progress that should
      encourage surgeons to incorporate computer simulation into the surgical
      curriculum.

PMID- 10896372
TI  - Hand-assisted laparoscopic vertical banded gastroplasty: report of a series.
AB  - HYPOTHESIS: Hand-assisted laparoscopic vertical banded gastroplasty is
      technically feasible and has weight loss and morbidity outcomes similar to those
      of the standard open technique. DESIGN: Patients in this study met the
      indications for bariatric surgery and were followed up prospectively for
      postoperative morbidity, mortality, and weight loss. PATIENTS: A total of 26
      patients with an average body mass index (calculated as weight in kilograms
      divided by the square of height in meters) of 50.8 underwent hand-assisted
      laparoscopic vertical banded gastroplasty. Follow-up ranged from 3 to 18 months.
      RESULTS: The hand-assisted technique was carried out efficiently, with low
      operative morbidity and no mortality. Weight loss during follow-up was similar to
      that described for the open technique. CONCLUSIONS: Hand-assisted laparoscopic
      vertical banded gastroplasty is technically feasible and has weight loss and
      morbidity outcomes similar to those of the open technique in this first report of
      a series. The hand-assisted technique greatly facilitates performance of the
      procedure over the completely laparoscopic procedure and yet retains the
      advantages realized by laparoscopic surgery.

PMID- 10896373
TI  - Laparoscopic antireflux surgery in the treatment of gastroesophageal reflux in
      patients with Barrett esophagus.
AB  - BACKGROUND: Patients with gastroesophageal reflux and Barrett esophagus may
      represent a group of patients with poorer postoperative outcomes. It has been
      suggested that such patients should undergo open rather than laparoscopic
      antireflux surgery. HYPOTHESIS: The laparoscopic approach to antireflux surgery
      is appropriate treatment for patients with Barrett esophagus who have symptomatic
      gastroesophageal reflux disease. METHODS: The outcome of 757 patients undergoing
      laparoscopic surgery for gastroesophageal reflux disease from January 1, 1992,
      through December 31, 1998, was prospectively examined. Barrett esophagus was
      present in 81 (10.7%) of these patients (58 men and 23 women). The outcome for
      this group of patients was compared with that of patients undergoing surgery who
      did not have Barrett esophagus. RESULTS: The types of operation performed were
      similar for the 2 patient groups. The mean +/- SD length of columnar mucosa was
      47.4 +/- 43.6 mm. The average +/- SD operation time was 79.0 +/- 33.4 minutes.
      Conversion to open surgery occurred in 6 patients. Postoperative outcomes were as
      follows. Esophageal manometry and 24-hour pH studies before and after
      laparoscopic fundoplication demonstrated a significant increase in lower
      esophageal sphincter resting and residual relaxation pressures and a significant
      decrease in distal esophageal acid exposure. Four patients have developed high
      grade dysplasia or invasive cancer within 4 years of their antireflux surgery,
      and all of these have subsequently undergone esophageal resection. CONCLUSIONS:
      The outcome of laparoscopic antireflux surgery is similar for patients with
      Barrett esophagus compared with other patients with gastroesophageal reflux
      disease. This suggests that laparoscopic surgery is appropriate treatment for
      this patient group.

PMID- 10896374
TI  - Laparoscopy-assisted Billroth I gastrectomy compared with conventional open
      gastrectomy.
AB  - BACKGROUND: Although several studies compare surgical results of laparoscopic and
      open colonic resections, there is no study of laparoscopic gastrectomy compared
      with open gastrectomy. HYPOTHESIS: When compared with conventional open
      gastrectomy, laparoscopy-assisted Billroth I gastrectomy is less invasive in
      patients with early-stage gastric cancer. DESIGN: Retrospective review of
      operative data, blood analyses, and postoperative clinical course after Billroth
      I gastrectomy. SETTING: University hospital in Japan. PATIENTS: The study
      included 102 patients who were treated with Billroth I gastrectomy for early
      stage gastric cancer from January 1993 to July 1999: 49 with laparoscopy-assisted
      gastrectomy and 53 with conventional open gastrectomy. MAIN OUTCOME MEASURES:
      Demographic features examined were operation time; blood loss; blood cell counts
      of leukocytes, granulocytes, and lymphocytes; serum levels of C-reactive protein,
      interleukin 6, total protein, and albumin; body temperature; weight loss;
      analgesic requirements; time to first flatus; time to liquid diet; length of
      postoperative hospital stay; complications; proximal margin of the resected
      stomach; and number of harvested lymph nodes. RESULTS: Significant differences
      (P<.05) were present between laparoscopy-assisted and conventional open
      gastrectomy when the following features were compared: blood loss (158 vs 302
      mL), leukocyte count on day 1 (9.42 vs 11.14 x 10(9)/L) and day 3 (6.99 vs 8.22 x
      10(9)/L), granulocyte count on day 1 (7.28 vs 8.90 x 10(9)/L), C-reactive protein
      level on day 7 (2.91 vs 5.19 mg/dL), interleukin 6 level on day 3 (4.2 vs 26.0
      U/mL), serum albumin level on day 7 (35.6 vs 33.9 g/L), number of times
      analgesics given (3.3 vs 6.2), time to first flatus (3.9 vs 4.5 days), time to
      liquid diet (5.0 vs 5.7 days), postoperative hospital stay (17.6 vs 22.5 days),
      and weight loss on day 14 (5.5% vs 7.1%). There was no significant difference
      between laparoscopy-assisted and conventional open gastrectomy with regard to
      operation time (246 vs 228 minutes), proximal margin (6.2 vs 6.0 cm), number of
      harvested lymph nodes (18.4 vs 22.1), and complication rate (8% vs 21%).
      CONCLUSIONS: Laparoscopy-assisted Billroth I gastrectomy, when compared with
      conventional open gastrectomy, has several advantages, including less surgical
      trauma, less impaired nutrition, less pain, rapid return of gastrointestinal
      function, and shorter hospital stay, with no decrease in operative curability.
      When performed by a skilled surgeon, laparoscopy-assisted Billroth I gastrectomy
      is a safe and useful technique for patients with early-stage gastric cancer.

PMID- 10896375
TI  - Portoenterostomy: an old treatment for a new disease.
AB  - HYPOTHESIS: Portoenterostomy may be an effective treatment for patients
      sustaining a thermal injury to the hepatic duct confluence during laparoscopic
      cholecystectomy. DESIGN: Case series. SETTING: A tertiary care referral hospital.
      PATIENTS: A consecutive series of 5 female patients referred and treated between
      November 13, 1991, and December 17, 1998. Ages ranged from 29 to 65 years. In
      addition to the ductal injuries at or above the hepatic duct confluence, 3
      patients also had a major hepatic vascular injury. The patients were available
      for follow-up for 7 to 91 months postoperatively. INTERVENTIONS: All patients
      underwent a portoenterostomy (Kasai procedure) with suturing of a Roux limb to
      the hepatic tissue surrounding the transected hepatic ducts. Transhepatic stents
      were inserted either preoperatively or postoperatively for rising liver enzyme
      levels in 4 patients. MAIN OUTCOME MEASURES: Symptoms and results of liver
      function tests. RESULTS: Stents remained in place for 9 to 25 months in 4
      patients. All 5 patients were symptom free and functioning normally; 3 had normal
      liver functions; 2 had mildly elevated alkaline phosphatase levels only.
      CONCLUSION: Portoenterostomy, usually in combination with postoperative stenting,
      may be an option to consider in life-threatening injuries involving the hepatic
      duct bifurcation in which standard biliary reconstruction techniques are not
      feasible.

PMID- 10896376
TI  - The influence of 2 surgical bandage systems on wound tissue oxygen tension.
AB  - HYPOTHESIS: Local wound heating improves tissue oxygen tension in postoperative
      patients. SETTING: University hospital. PATIENTS: Forty normothermic and well
      hydrated patients recovering from elective open abdominal surgery. INTERVENTIONS:
      A comparison between an experimental bandage system (Warm-Up; Augustine Medical
      Inc, Eden Prairie, Minn) and conventional gauze covered with elastic adhesive
      (Medipore Dress-it; 3M, St Paul, Minn). The experimental system is heated to 38
      degrees C and does not touch the wound. MAIN OUTCOME MEASURES: Subcutaneous
      tissue oxygen tension was measured postoperatively and on the first postoperative
      day. In a subgroup, we also evaluated the effects of bandage pressure per se on
      tissue oxygen. RESULTS: Initial postoperative tissue oxygen tensions were
      approximately 30 mm Hg greater with the experimental bandage, even before
      warming. Subcutaneous oxygen tension during heating remained significantly
      greater in patients with the warmed bandage than the conventional elastic bandage
      (116 +/- 40 vs 85 +/- 34 mm Hg, respectively) while the patients were breathing
      approximately 50% oxygen. The difference was smaller on the first postoperative
      day, but still statistically significant (82 +/- 30 vs 65 +/- 22 mm Hg,
      respectively). In the subgroup analysis, tissue oxygen tension increased
      significantly by 12 +/- 4 mm Hg when the heating bandage was substituted for a
      conventional bandage (P<.001). CONCLUSION: In normothermic and well-hydrated
      surgical patients, much benefit from the heating bandage system appears to result
      from pressure relief. These data suggest that relieving wound pressure markedly
      improves tissue perfusion and oxygenation.

PMID- 10896377
TI  - Decreasing length of stay after pancreatoduodenectomy.
AB  - HYPOTHESIS: Decreased length of stay (LOS) after pancreatoduodenectomy is due to
      multiple factors, including a lower complication rate and more efficient
      perioperative care for all patients, with and without complications. DESIGN: A
      retrospective review, validation cohort. SETTING: A single university hospital
      referral center. PATIENTS: A consecutive sample of patients undergoing
      pancreatoduodenectomy from January 9, 1986, to December 21, 1992 (group 1 [n =
      104]) and from February 16, 1993, to November 9, 1998 (group 2 [n = 111]).
      INTERVENTION: Mann-Whitney test and linear [correction of logistic] regression
      analysis applied to clinical variables and LOS. MAIN OUTCOME MEASURES: Difference
      in median LOS between early and late groups and identification of factors
      predictive of decreased LOS. RESULTS: Total LOS decreased between the 2 groups
      (26 days [range, 13-117 days] vs 15 days [range, 5-61 days]; P<.001), with a
      decrease in preoperative (4 days [range, 0-28 days] vs 2 days [range, 0-36 days];
      P<.001) and postoperative (19 days [range, 11-95 days] vs 12 days [range, 4-58
      days]; P<.001) LOS (data given for group 1 vs group 2). Major complications
      decreased from 49% in group 1 to 25% in group 2 (P<.001). Postoperative LOS
      decreased for patients with (25 days [range, 15-95 days] vs 20 days [range, 8-58
      days]; P = .05) and without (15 days [range, 11-47 days] vs 11 days [range, 4-55
      days]; P<.001) major complications (data given for group 1 vs group 2).
      Multivariate analysis identified age (P = .01), pancreatic fistula (P<.001),
      delayed gastric emptying (P<.001), biliary complications (P<.001), operative time
      (P<.005), extra-abdominal infection (P<.005), use of a percutaneous stent (P =
      .04), and year of operation (P<.001) as independent predictors of total LOS.
      CONCLUSION: A reduction in complications in combination with factors leading to a
      streamlining of perioperative care has contributed to the decreased LOS after
      pancreatoduodenectomy.

PMID- 10896379
TI  - Repeat victims of violence: report of a large concurrent case-control study.
AB  - HYPOTHESIS: Repeat victims of violence (violence victim recidivism) is a
      phenomenon known throughout the nation by those who work in hospital emergency
      departments. A level I trauma center in Baltimore, Md, conducted this study to
      investigate the postulated risk factors for repeat victims of violence, ie,
      unemployment, limited educational attainment, and involvement with illicit drug
      use or drug dealing. DESIGN: A case-control study identified 200 cases and 224
      controls during a 16-month period. Cases were persons admitted with traumatic
      injury secondary to violent assault who had been previously hospitalized for a
      similar reason. Controls were a random selection of eligible age- and sex-matched
      patients admitted for reasons unrelated to violent injury. RESULTS: Prominent
      risk factors associated with recidivism were African American male, median age 31
      years, unemployed, lacking medical insurance, annual income less than $10000,
      current drug user, past or present drug dealer, and a positive test for
      psychoactive substances on admission to the hospital. One hundred seventy-two
      (86%) of the cases felt that disrespect (called "dissing" in the local
      vernacular) was involved with their injury. CONCLUSIONS: The multiplicity of risk
      factors and the fact that they are interrelated mandate a comprehensive approach
      to the difficult problem of violence recidivism. Experiments in hospital-based
      intervention strategies are needed.

PMID- 10896378
TI  - Adenocarcinoma of the esophagus with and without Barrett mucosa.
AB  - HYPOTHESIS: Previous studies have demonstrated an improved prognosis in patients
      with Barrett adenocarcinoma as compared with esophageal adenocarcinoma without
      Barrett. It has been suggested that an earlier presentation due to
      gastroesophageal reflux disease (GERD) may lead to detection of adenocarcinoma at
      an earlier stage. DESIGN: The records of 178 patients with esophageal
      adenocarcinoma presenting to Roswell Park Cancer Institute (Buffalo, NY) between
      1991 and 1996 were reviewed. MAIN OUTCOME MEASURES: The clinical presentation,
      work-up, therapy, and outcome were compared between patients with Barrett
      esophagus (n = 66) and those without endoscopic or pathologic evidence of Barrett
      esophagus (n = 112). RESULTS: There were several favorable prognostic signs in
      the Barrett group, including smaller tumors, lower grade, and earlier stage. More
      patients in the Barrett group had surgically resectable tumors, resulting in an
      improved overall survival. However, there were no differences in the type or
      duration of symptoms. Overall, very few patients presented because of GERD, and
      only slightly more in the Barrett group (14% vs 4%). While survival greatly
      improved in patients diagnosed with Barrett due to GERD, this did not account for
      the difference in prognosis. CONCLUSIONS: Improved prognosis and survival for the
      Barrett group is not due to earlier presentation due to symptoms of GERD. It is
      more likely that all esophageal adenocarcinoma arises from Barrett esophagus, and
      that it is obscured by larger tumors. Reviews limited to resected patients
      greatly overestimate the number of adenocarcinoma cases diagnosed due to GERD.
      Increased efforts to identify high-risk patients and initiate screening are
      necessary to diagnose adenocarcinoma at an earlier stage.

PMID- 10896380
TI  - Preoperative sestamibi scanning and surgical findings at bilateral, unilateral,
      or minimal reoperation for recurrent hyperparathyroidism after subtotal
      parathyroidectomy in patients with multiple endocrine neoplasia type 1.
AB  - HYPOTHESES: Preoperative parathyroid radioisotope scanning is of little or no
      value in patients with multiple endocrine neoplasia type 1 when 4 or more
      hypertrophied glands are present. Scanning using technetium Tc 99m sestamibi and
      single photon emission computed tomography will achieve a high level of
      sensitivity and specificity after 3 or more glands have previously been removed,
      justifying limited surgical reexploration. DESIGN: In a prospective study, the
      preoperative documented report of the predicted site of residual parathyroid was
      compared with the surgical findings in 13 patients having 19 scans and 17
      reoperations. SETTING: All patients belonged to one family, previously described
      as Tasman family 1, and were confirmed by genetic testing as having multiple
      endocrine neoplasia type 1. In 10 of 13 patients, reexploration was being
      undertaken more than 10 years after the first operation. MAIN OUTCOME MEASURES:
      Scanning was regarded as successful when the documented preoperative report
      correctly predicted the side and quadrant in which a gland was found at surgery.
      Surgery was regarded as successful when calcium levels decreased to or below
      normal levels and were maintained. RESULTS: All 13 scans before first
      reexploration were successful in identifying the location of a residual
      parathyroid. From a statistical viewpoint, this equates to 100% sensitivity and
      92% specificity. However, despite accurate localization of 1 residual gland in
      every patient, 7 supernumerary glands in 4 patients and 1 parathyroid remnant in
      a fifth patient were not localized so that sensitivity in locating all glands in
      every patient was only 61%. Scans performed for persistent hypercalcemia 48 to 72
      hours after reexploration in 2 patients were unsuccessful in demonstrating any
      residual parathyroid. Scans performed 3 months after surgery in the same 2
      patients and a third patient were successful, with sensitivity and specificity of
      100%. Apart from patient 11, who awaits reexploration, normocalcemia was
      eventually achieved in every patient, with 11 of 12 having an initial period of
      hypocalcemia. CONCLUSIONS: Three months after reexploration and trimming or
      resection with transplant of half a gland left at first operation, sestamibi
      scanning achieved sensitivity and specificity of 100% in locating supernumerary
      parathyroids in patients with multiple endocrine neoplasia type 1 and persistent
      hypercalcemia. Before first reexploration, however, scans rarely provided new
      information, predominantly showing only the hypertrophied half-gland remnant.

PMID- 10896381
TI  - An evaluation of telemedicine in surgery: telediagnosis compared with direct
      diagnosis.
AB  - HYPOTHESIS: Telemedicine for real-time transmission of clinical documents and
      interactive remote telediagnosis allows accurate clinical application in surgery.
      DESIGN: Prospective cohort study in which 2 hospitals, 120 miles apart, were
      connected via integrated services digital network (ISDN) teleconferencing units,
      and each evaluated clinical cases in real time. SETTING: A tertiary care
      university hospital and primary care county hospital. PARTICIPANTS: Between May
      1, 1998, and June 30, 1998, 112 patients undergoing digestive or endocrine
      surgery were evaluated by teletransmission (study group) and direct vision
      (control group). Diagnosis had to be known by the viewer, and either conventional
      magnetic resonance imaging or computed tomographic scans were available. MAIN
      OUTCOME MEASURES: Picture quality, organ structure, and pathologic finding viewed
      on telemedicine documents were evaluated by radiologists and surgeons blind to
      diagnosis. Accuracy of remote 128-kilobit (kb)/s transmission-rate diagnoses and
      results were compared with those obtained directly. RESULTS: Picture quality was
      "good" or "excellent" in 92.9% of transmitted documents and 95.5% of live images
      (P>.4). The target organ was always recognized, structure and pathologic finding
      were analyzable in 98.2% of transmitted documents and 99.1% of live documents,
      and fine structures were assessable in 89.3% of transmitted pictures and 95.5% of
      live pictures (P>.05). Diagnosis was made in 84.8% of transmitted cases and 93.8%
      of live cases (P = .02). CONCLUSIONS: Low bandwidth (128 kb/s) telemedicine
      application in surgery is reliable in evaluating remote cases. Loss of image
      quality through teletransmission occurred in 2.7% of cases, and diagnosis was not
      possible in 15.2% of transmitted vs 6.2% of live cases, suggesting factors other
      than technical quality (choice of radiological studies, additional clinical
      information required, etc). This underscores the importance of real-time
      interactive discussion during surgical teleconferences.

PMID- 10896382
TI  - Hand-assisted laparoscopic liver resection: lessons from an initial experience.
AB  - BACKGROUND: Recent innovations in laparoscopic instrumentation make routine
      resection of solid organs a clinical possibility. HYPOTHESIS: Hand-assisted
      laparoscopic liver resection is a safe and feasible procedure for solitary
      cancers requiring removal of 2 segments of liver or less. DESIGN AND PATIENTS:
      Eleven patients with liver tumors deemed technically resectable by laparoscopic
      techniques were subjected to laparoscopic evaluation and attempted hand-assisted
      laparoscopic resection between July 1998 and July 1999. During the same period,
      230 patients underwent open liver resection. SETTING: Tertiary care referral
      center for liver cancer. MAIN OUTCOME MEASURES: Success of laparoscopic
      resection, reasons for conversion to open liver resection, blood loss, tumor
      clearance margin, complications, and length of hospital stay. RESULTS: Five
      patients underwent successful resection by the hand-assisted laparoscopic
      technique. Data from the 5 successful cases and the 6 aborted cases are presented
      to outline the issues and the lessons learned. CONCLUSIONS: In selected patients,
      hand-assisted laparoscopic liver resection can be safely performed and might have
      potential advantages over traditional liver resection if the tumor is limited to
      the left lateral segment or is at the margins of the liver.

PMID- 10896384
TI  - Classroom instruction: "a blast".

PMID- 10896383
TI  - Induction of the stress response in vivo decreases nuclear factor-kappa B
      activity in jejunal mucosa of endotoxemic mice.
AB  - BACKGROUND: Results of previous studies suggest that the stress response protects
      cells and tissues by regulating proinflammatory mediators. The transcription
      factor nuclear factor-kappa B (NF-kappa B), normally sequestered in the cytoplasm
      by its inhibitory protein, I kappa B, regulates many genes involved in
      inflammatory responses to critical illness. Endotoxemia is associated with
      increased NF-kappa B activity in intestinal mucosa, but the effect of the stress
      response on endotoxin-induced NF-kappa B activation in intestinal mucosa is not
      known. HYPOTHESIS: Induction of the stress response inhibits NF-kappa B DNA
      binding activity in jejunal mucosa during endotoxemia. METHODS: The stress
      response was induced in mice by hyperthermia (42 degrees C) or injection with
      sodium arsenite (10 mg/kg). After 2 to 5 hours, mice were injected with endotoxin
      (lipopolysaccharide, 12.5 mg/kg) or a corresponding volume of sterile saline. One
      hour later, jejunal mucosa was harvested for preparation of nuclear and
      cytoplasmic extracts. RESULTS: Mucosal levels of heat shock protein-72 increased
      after hyperthermia or treatment with sodium arsenite, consistent with induction
      of the stress response. The increase in NF-kappa B DNA binding activity and
      decrease in I kappa B-alpha levels seen after endotoxin injection were inhibited
      by previous induction of the stress response. CONCLUSION: The protective effects
      of the stress response in vivo might, at least in part, be due to inhibited NF
      kappa B activation.

PMID- 10896385
TI  - American Surgical Association.

PMID- 10896386
TI  - Interleukin 10 and sepsis.

PMID- 10896387
TI  - Hand-assisted laparoscopic aortoiliac surgery.

PMID- 10896388
TI  - A patient's right to truly informed consent.

PMID- 10896389
TI  - Equine viral arteritis.
AB  - Equine viral arteritis (EVA) can cause prominent economic losses for the equine
      industry. The purpose of this review is to provide the pathologist some
      familiarity with the clinical history, lesions, pathogenesis, and diagnosis of
      EVA. EVA is caused by an arterivirus (equine arteritis virus, EAV), and the
      vascular system is the principal but not unique viral target. EVA has variable
      presentations, including interstitial pneumonia, panvasculitis with edema,
      thrombosis and hemorrhage, lymphoid necrosis, renal tubular necrosis, abortion,
      and inflammation of male accessory genital glands. EAV antigen (EAVAg) can be
      demonstrated within the cytoplasm of epithelial cells such as alveolar
      pneumocytes, enterocytes, adrenal cortical cells, trophoblasts, thymus stroma,
      renal tubular cells, and male accessory genital gland cells. It can be also
      demonstrated within endothelia, in vascular, myometrial, and cardiac myocytes,
      macrophages, dendritelike cells of lymphoid organs, and chorionic mesenchymal
      stromal cells. In young and adult horses, following colonization of macrophages,
      the virus spreads systemically using circulating monocytes and enters the
      endothelium and tunica media of blood vessels, histiocytes, and dendritelike
      cells. Eventually, the virus multiplies within renal tubular cells. Lesions are
      uncommon in the aborted fetus; if present, they are mild, and EAVAg is frequently
      not detectable within fetal tissues and placenta. The clinical presentation and
      lesions of EVA may resemble those of other diseases. Complete pathologic
      examination associated with immunohistochemistry, virus isolation, and,
      especially in cases of abortion, serology will guarantee a directed and accurate
      diagnosis.

PMID- 10896390
TI  - Evaluation of angiogenesis in canine mammary tumors by quantitative platelet
      endothelial cell adhesion molecule immunohistochemistry.
AB  - Angiogenesis was evaluated by immunohistochemistry for platelet endothelial cell
      adhesion molecule (CD31) in a series of benign and malignant canine mammary
      neoplasms. Computer image analysis was used to measure the intratumoral
      microvessel density (number of microvessels per square millimeter) and the area
      and perimeter of immunolabeled vascular structures. A higher intratumoral
      microvessel density and lower values for area and perimeter were found in
      malignant neoplasms compared with benign tumors and among the malignant tumors,
      in less differentiated phenotypes and in more anaplastic histological types
      (solid and squamous carcinomas), most of which had metastasized. These findings
      are consistent with an increase in angiogenesis in multistage neoplasia.
      Therefore, in more anaplastic malignant neoplasms, numerous but small and often
      malformed new vessels can be identified. The correlation of angiogenesis data
      with differentiation grade and histological type of mammary neoplasms is
      consistent with the findings in human medicine and demonstrates that angiogenesis
      can also have a prognostic value in veterinary medicine.

PMID- 10896391
TI  - Autoantibodies against the processed ectodomain of collagen XVII (BPAG2, BP180)
      define a canine homologue of linear IgA disease of humans.
AB  - Linear IgA disease (LAD) is an acquired autoimmune subepidermal blistering
      dermatosis that affects human children and adults. In contrast to bullous
      pemphigoid, in which autoantibodies recognize transmembrane type XVII collagen
      (BP180, BPAG2), LAD is associated with skin-fixed and circulating IgA
      autoantibodies that target LAD-1, the processed extracellular form of type XVII
      collagen. An immunologic homologue of LAD in humans was identified in two dogs
      according to the following criteria: 1) erosive, ulcerative, and crusted lesions
      seen on the face, in the oral cavity, and on the extremities, 2) dermoepidermal
      clefting present in the basement membrane lamina lucida without inflammation or
      with mild neutrophilic infiltration, 3) basement membrane-fixed IgG and/or IgA
      antibodies, and 4) circulating IgA and IgG autoantibodies that target the 120-kd
      soluble protein LAD-1. The present study establishes unequivocally the existence
      of a naturally occurring canine model of LAD of humans.

PMID- 10896392
TI  - Canine large granular lymphocyte leukemia and its derived cell line produce
      infectious retroviral particles.
AB  - We describe a case of large granular lymphocyte (LGL) leukemia in a dog that we
      followed over a period of 2 years. Analysis of a hematological profile revealed
      lymphocytosis (19,500 lymphocytes per microliter; reference values, 1,000-4,800
      lymphocytes per microliter), with a majority of LGL on the blood smear. LGL is
      defined as a lymphoid subset comprising 10% of peripheral blood mononuclear cells
      and corresponding to either CD3- CD8- NK cells or CD3+ CD8+ T cells. The cells
      are characterized by abundant basophilic cytoplasm containing distinct granules
      of variable size and number. The characteristic phenotype of our leukemic LGL is
      of a cytotoxic T cell, CD3+ and CD8+. A new cell line, DLC 02, was established
      from the peripheral lymphocytes of the leukemic dog. Particles with type C
      retroviral morphology were found in ultrathin sections of DLC 02 cell pellets.
      These particles were found to have a sucrose gradient density of 1.17 g/liter and
      a reverse transcriptase activity with an Mn2+ preference, suggesting that they
      correspond to a mammalian type C oncovirus.

PMID- 10896393
TI  - Vascular ultrastructure and DNA fragmentation in swine infected with Shiga toxin
      producing Escherichia coli.
AB  - Shiga toxins (Stx) produced by Escherichia coli cause systemic vascular damage
      that manifests as edema disease in swine and hemolytic uremic syndrome in humans.
      In vitro, Stx inhibit protein synthesis and, depending on circumstances, induce
      necrosis, apoptosis, or both. The mechanism of in vivo Stx-mediated vascular
      damage is not known. The ability of Stx to cause apoptosis of vasculature in vivo
      was studied in pigs with edema disease that was produced by oral inoculation with
      Stx-producing E. coli. Arterioles of ileum and brain were evaluated by terminal
      dUTP nick-end labeling (TUNEL) assay for DNA fragmentation in myocytes (10
      infected pigs, 5 control pigs) and by transmission electron microscopy for
      ultrastructural changes characteristic of apoptosis (17 infected pigs, 8 control
      pigs). In comparison with controls, increased numbers of TUNEL-positive
      arterioles were detected in 6/10 (60%) subclinically affected pigs 14-15 days
      after inoculation. Ultrastructurally, lesions in myocytes consisted of lysis
      (necrosis), with cytoplasmic debris and nuclear fragments contained between
      intact basement membranes. Endothelial cell changes ranged from acute swelling to
      necrosis and detachment from basement membrane. Subclinically affected pigs (n =
      14) tended to have changes predominantly in myocytes, whereas pigs with clinical
      illness (n = 3) more commonly had changes in endothelial cells. The arteriolar
      lesions and clinical signs of edema disease are attributed to the effects of Stx
      on vasculature. Therefore, our findings suggest that the Stx-induced arteriolar
      lesions seen in this study were primarily necrotic, not apoptotic. We suspect
      that necrosis was the principal cause of the DNA fragmentation detected.

PMID- 10896394
TI  - Connective tissue growth factor expression in the rat remnant kidney model and
      association with tubular epithelial cells undergoing transdifferentiation.
AB  - Connective tissue growth factor (CTGF) has been shown to mediate many actions of
      transforming growth factor-beta (TGF-beta) in the fibrotic response in several
      diseases. We compared expression of CTGF, TGF-beta, platelet-derived growth
      factor (PDGF), TNF-alpha, and interleukin-1 (IL-1) by in situ hybridization in
      Sprague-Dawley rats euthanized at 0, 2, 4, and 8 weeks after 5/6 nephrectomy
      using the rat remnant kidney model of renal failure. Collagen was evaluated by
      trichrome stains, immunohistochemistry, and electron microscopy. We compared
      expression patterns to cells undergoing metaplasia. Tubular epithelial
      regeneration and transdifferentiation to myofibroblasts were assessed
      morphologically and by proliferating cell nuclear antigen, smooth muscle actin,
      desmin, and vimentin immunohistochemistry. CTGF expression was minimal in
      controls, mild at 2 weeks and marked by 4 to 8 weeks in interstitial fibroblasts,
      coinciding with damage, regeneration, and fibrosis. TGF-beta expression was
      increased in many cell types at 2 weeks, increased further by 4 weeks, then
      remained constant. PDGF-B messenger RNA was found in many stromal cells at 2-4
      weeks, but expression decreased at 8 weeks. No significant IL-1 or TNF-alpha
      staining was detected. We conclude that CTGF and interacting factors are
      associated with development or progression of chronic interstitial fibrosis.
      Proximity of CTGF, TGF-beta, and PDGF mRNA expression to regenerative epithelial
      cells and those transdifferentiating to myofibroblasts suggests that growth
      factors may modulate renal tubular epithelial differentiation.

PMID- 10896395
TI  - Rudimentary hemidesmosome formation in congenital generalized junctional
      epidermolysis bullosa in the Sprague-Dawley rat.
AB  - Seven of 14 newborn pups in a litter of Sprague-Dawley rats were found to have
      generalized detachment of the epidermis, which was thin, wrinkled, and hung in
      loose folds over distal extremities. Histologic and ultrastructural examination
      of the skin showed noninflammatory separation of the epidermis from the dermis at
      the lamina lucida of the basement membrane zone. Ultrastructurally,
      hemidesmosomes were small and had a rudimentary appearance; keratin tonofilaments
      in basal keratinocytes were detached from the hemidesmosomes. The skin lesions
      were consistent with generalized junctional epidermolysis bullosa, which has not
      previously been reported in the rat. In humans, generalized junctional
      epidermolysis bullosa is most commonly caused by autosomal recessive inheritance
      of defective proteins of the hemidesmosomes or anchoring filaments. The specific
      protein defect involved in the rat lesion was not determined because fresh frozen
      tissue was not available.

PMID- 10896396
TI  - Ganglion cysts in a juvenile dog.
AB  - Ganglion cysts were diagnosed in a 4-month-old male Afghan Hound. Grossly, the
      subcutaneous ovoid cysts around the caudal right elbow joint and left ischiatic
      tuberosity had abundant mucinous fluid and internal folding. The lesions recurred
      twice around the elbow joint after surgical removal. Neither cyst communicated
      with the joint cavity. Histologically, the cyst wall consisted of inner
      myxomatous and outer immature connective tissue. Some parts of the cyst wall had
      various stages of myxoid metaplasia of collagen tissue leading to new cyst
      formation. Ultrastructural study revealed that cells in the myxoid metaplastic
      lesion had well-developed cytoplasmic secretory elements, including abundant
      rough endoplasmic reticulum, Golgi apparatus, and many smooth-walled vesicles.
      These ganglion cysts apparently resulted from the metaplasia of fibroblasts to
      secreting cells.

PMID- 10896397
TI  - Squamous cell carcinoma in an American bison (Bison bison bison).
AB  - The following case report is, to the best of our knowledge, the first
      documentation of a squamous cell carcinoma in a full-blooded American bison
      (Bison bison bison). This female bison developed an ulcerated lesion on the left
      flank, at the site of a brand, in the summer of her eighth year. In the winter of
      her ninth year, as the lesion continued to grow, a biopsy was performed, and a
      diagnosis of squamous cell carcinoma was made. Ultimately, there was metastasis
      to the liver, a lung, and a prefemoral lymph node.

PMID- 10896398
TI  - Calcium hydroxylapatite deposition disease in a Great Dane Puppy.
AB  - A 10-week-old male Great Dane Puppy was presented for sudden onset tetraataxia
      and severe paresis of the front legs. Mineral deposits were detected
      radiographically, at gross postmortem examination, and light microscopically
      between the vertebral arches of multiple cervical and lumbar vertebrae. These
      deposits were associated with the interarchial ligaments (ligamentia
      interarcualia), along the interfaces of the synovium and articular cartilage of
      multiple cervical, thoracic, and lumbar facets, on the dorsal aspect of several
      thoracic intervertebral discs, and at the insertion of muscles at the lateral
      aspect of several cervical and thoracic vertebral bodies. The mineral deposits
      were associated with a granulomatous inflammation and synovial fibrocartilaginous
      metaplasia and proliferation, which was focally exuberant. X-ray diffraction
      analyses of the mineral deposits revealed calcium hydroxylapatite as the major
      component. The clinical signs in this puppy were due to focal compression of the
      spinal cord by marked extraarticular ligament-associated fibrocartilaginous
      proliferation.

PMID- 10896400
TI  - A pleomorphic adenoma of the lacrimal gland in a dog.
AB  - A 13-year-old female mongrel dog had a pleomorphic adenoma of the lacrimal gland
      in the right upper orbit. The tumor measured 3.8 x 3.0 x 3.3 cm, appeared white,
      round, and firm, and pressed the right globe and surrounding tissues.
      Histopathologically, the tumor had a thin connective tissue capsule and was
      composed of tubules with two cell types, some resembling luminal epithelial cells
      making up the tubular structures and the other of myoepithelial cells. Epithelial
      tubules were disposed in an adenomatous fashion and separated from each other by
      proliferating pleomorphic myoepithelial cells. Immunohistochemically, large
      numbers of the luminal epithelial cells revealed an immunopositive reaction
      against keratin/cytokeratin (AE1/AE3), and some epithelial cells reacted against
      cytokeratin 14. Spindle-shaped myoepithelial cells revealed an immunopositive
      reaction against cytokeratin 14, alpha-smooth muscle actin, and vimentin. A small
      number of myoepithelial cells reacted against desmin. S-100 protein
      immunopositivity was frequently found in luminal epithelial cells and rarely in
      the pleomorphic myoepithelial cells. Glial fibrillary acidic protein positivity
      was commonly found in myoepithelial cells, myxoid matrices, and intracystic
      materials, but not in luminal epithelial cells.

PMID- 10896399
TI  - Malignant fibrous histiocytoma (giant cell type) associated with a malignant
      mixed tumor in the salivary gland of a dog.
AB  - A 12-year-old male Boxer dog presented with a 5 x 5 x 7-cm partially encapsulated
      mass in the right mandibular salivary gland. Histologically, the mass was
      composed of neoplastic epithelial and mesenchymal cells. The mesenchymal
      component consisted of two cell populations arranged in different patterns:
      coalescing nodules of neoplastic mononuclear cells with rare osteoid and numerous
      osteoclastlike giant cells; and sheets of neoplastic spindle cells intermingled
      with neoplastic epithelial cells and containing osteoid and well-formed bone
      trabeculae lined by osteoblasts and few osteoclastlike giant cells. On the basis
      of these histological features, two malignant salivary tumors were diagnosed: a
      malignant fibrous histiocytoma (giant cell type) and a malignant mixed tumor.
      Immunohistochemical studies demonstrated keratin 5 and 8 expression by the
      neoplastic epithelial cells, indicating a probable salivary ductal origin, and
      vimentin expression by all mesenchymal elements, suggesting a fibroblastic line
      of differentiation.

PMID- 10896401
TI  - Synovial sarcoma in an Ayrshire heifer.
AB  - An 8-month-old Ayrshire heifer had a rapidly growing mass in the axillary region
      of the left thoracic limb. The mass surrounded the distal humerus and entrapped
      nerves of the brachial plexus, causing an abnormal gait. Histologically, the mass
      was composed of clusters and cords of round to polygonal cells with scattered,
      spindle-shaped cells. The neoplastic cells stained positively for vimentin and
      cytokeratin. No staining was found with S-100 protein, kappa and lambda light
      chains, or T-cell markers by immunohistochemistry. On electron microscopic
      evaluation, the cytoplasm of the neoplastic cells contained few organelles,
      principally rough and smooth endoplasmic reticulum and mitochondria. This
      synovial sarcoma has histologic and ultrastructural features characteristic of
      the poorly differentiated subtype of synovial sarcoma in the human classification
      system.

PMID- 10896402
TI  - Bovine teat atresia associated with horn fly (Haematobia irritans irritans (L.))
      induced dermatitis.
AB  - Mammary gland lesions characterized primarily as mammary teat atresia were
      observed in a Limousin beef cattle herd in eastern Texas. Atresia of multiple
      teats per mammary gland was reported in first-calf heifers at the time of
      calving. Pathogens were not identified in eight mammary glands collected at
      slaughter. Histology of affected glands demonstrated superficial and deep
      perivascular inflammation and fibrosing dermatitis of teat and mammary gland skin
      that resulted in formation of the atretic lesions of glandular tissue.
      Institution of a horn fly (Haematobia irritans irritans (L.)) control program
      using insecticide-impregnated ear tags was associated with elimination of the
      problem from the herd.

PMID- 10896403
TI  - Multiple myeloma in cats: variable presentation with different immunoglobulin
      isotypes in two cats.
AB  - Multiple myeloma was diagnosed in two cats with monoclonal hyperglobulinemia,
      proteinuria, and plasma cell proliferations in bone marrow. An immunoglobulin G
      producing myeloma occurred in the vertebral bone marrow of one cat, and twice
      responded to surgical reduction followed by a combination of local irradiation
      and chemotherapy. The cat's survival time was approximately 2 years. The other
      myeloma in a cat that presented with hypercalcemia and renal insufficiency
      involved visceral organs and produced a biclonal peak due to immunoglobulin A
      dimer formation on serum electrophoresis. This cat's tumor did not respond to
      chemotherapy.

PMID- 10896404
TI  - Recent references.

PMID- 10896405
TI  - Time course of neurone-specific enolase and S-100 protein release during and
      after coronary artery bypass grafting.

PMID- 10896406
TI  - Time Course of neurone-specific enolase and S-100 protein release during and
      after coronary artery bypass grafting.

PMID- 10896407
TI  - Computerized survelliance of adverse drug reactions in hospital: pilot study.
AB  - AIMS: To develop and assess the use of computerized laboratory data as a
      detection support tool of adverse drug reactions (ADRs) in hospital. METHODS:
      This was a retrospective observational study of 153 sequential medical admissions
      during a 2-month period to the 34-bed medical ward at the Hadassah University
      Hospital, Jerusalem, Israel. Measurements made were 1) Retrospective chart review
      for recognized and unrecognized adverse drug reactions (ADRs) and 2) Analysis of
      computerizied laboratory data according to defined automatic laboratory signals
      (ALS) for adverse reactions. RESULTS: Forty ADRs have been detected in 38 out of
      the 153 hospital admissions (24.8%). Nine reactions were considered severe.
      Altogether 212 ALS were generated involving 86 admissions. In 25 (65.8%) of the
      ADR-positive admissions ADRs were detected through automatic signals generated
      from the laboratory data. ALS were detected in 56 out of the 115 (48.7%) ADR
      negative admissions. Twenty-four (60%) of the ADRs were not recognized as such by
      the attending physicians. Two of these reactions were severe. ALS could have
      generated an alert for 19 (79.2%) of the unrecognized reactions. CONCLUSIONS:
      Application of automatic laboratory signals can increase the rate of recognition
      of the ADRs and thereby improve medical care. The sensitivity and specificity of
      the method might be increased by refinement and redefinition of the signals.

PMID- 10896408
TI  - Halofantrine and chloroquine inhibit CYP2D6 activity in healthy Zambians.
AB  - AIMS: To determine the effect of therapeutic loading doses of halofantrine and
      chloroquine on CYP2D6 activity in healthy black Zambians. METHODS: Twenty healthy
      black male Zambians were phenotyped for CYP2D6 activity by measuring the
      debrisoquine/4-hydroxydebrisoquine ratio in a 0-8 h urine sample after a 10 mg
      oral dose of debrisoquine hemi-sulphate. The subjects (all 'extensive
      metabolizer' phenotype with respect to CYP2D6) were randomized into two groups of
      10, and 24 h later one group received 1500 mg halofantrine hydrochloride and the
      other group 1500 mg chloroquine phosphate both orally in divided doses. All
      subjects were given further 10 mg doses of debrisoquine at 2 h, 1 week and 2
      weeks after the last dose of the antimalarial drug, and phenotyped as described
      above. RESULTS: The median debrisoquine/4-hydroxydebrisoquine 0-8 h urinary ratio
      was increased by halofantrine (1.39 to 6.05; P<0.01; 95% confidence intervals
      4.00-11.7) and chloroquine (1.96 to 3.91; P<0.01; 95% confidence intervals 1.34
      2.66) when debrisoquine was given 2 h after treatment. The decrease in CYP2D6
      activity remained statistically significant for 1 week after both drugs.
      Halofantrine was a significantly more potent inhibitor of CYP2D6 than chloroquine
      (P=0.037). Phenocopying occurred in two subjects taking halofantrine and one
      taking chloroquine (i.e. the debrisoquine/4-hydroxydebrisoquine ratios became
      consistent with the poor metabolizer phenotype). CONCLUSIONS: Given in
      therapeutic loading doses, both halofantrine and chloroquine caused significant
      inhibition of CYP2D6 activity in healthy black Zambians. With respect to
      halofantrine, this finding reinforces the recommendation that its combination
      with other drugs known to prolong the QT interval should be avoided, especially
      those that are metabolized significantly by CYP2D6.

PMID- 10896409
TI  - Terfenadine-antidepressant interactions: an in vitro inhibition study using human
      liver microsomes.
AB  - AIMS: Inhibition of the metabolism of terfenadine has been associated with
      torsades de pointes ventricular arrhythmias. The aim of this study was to assess
      in vitro the potency of the antidepressants nefazodone, sertraline and fluoxetine
      in inhibiting terfenadine biotransformation. METHODS: Human liver microsomes were
      incubated with terfenadine and the antidepressants at various concentrations.
      Formation of the two major metabolites of terfenadine was determined by h.p.l.c.
      RESULTS: The apparent Km for microsomes from four human livers was 11+/-5 and
      18+/-3 microM (mean +/-s.e.mean) for the N-dealkylation and C-hydroxylation
      pathways, respectively. Nefazodone, sertraline and fluoxetine inhibited
      terfenadine N-dealkylation with K(i) values of 10+/-4, 10+/-3 and 68+/-15 microM
      respectively. Inhibition of the C-hydroxylation pathway yielded noncompetitive
      K(i) values of 41+/-4, 67+/-13 and 310+/-40 microM respectively. CONCLUSIONS:
      Nefazodone and sertraline were moderately weak in vitro inhibitors of terfenadine
      metabolism while fluoxetine was a very weak inhibitor. Clinically significant
      interaction of terfenadine is more likely with nefazodone than sertraline or
      fluoxetine since therapeutic plasma levels of nefazodone are comparatively
      higher.

PMID- 10896410
TI  - A case of non-HFE juvenile haemochromatosis presenting with adrenocortical
      insufficiency.

PMID- 10896411
TI  - Two commonly used indices of thought disorder.

PMID- 10896412
TI  - Central serous chorioretinopathy may be a manifestation of the primary
      antiphospholipid syndrome.

PMID- 10896413
TI  - Acute retinal necrosis following chickenpox in a healthy 4 year old patient.

PMID- 10896414
TI  - Globe perforation with frameless spectacles.

PMID- 10896415
TI  - Ocular ectodermal syndrome of epibulbar dermoid and cutaneous myxovascular
      hamartoma.

PMID- 10896416
TI  - Foveal translocation with secondary confluent laser for subfoveal CNV in AMD: 12
      month follow up.

PMID- 10896417
TI  - The teardrop sign: a rare dermatological reaction to brimonidine.

PMID- 10896419
TI  - Re: "metabolic maladaptation: individual and social consequences of medical
      intervention in correcting endemic hypothyroidism".

PMID- 10896418
TI  - The oil droplet sign.

PMID- 10896420
TI  - A comment on "a glimpse into the process...".

PMID- 10896421
TI  - Re: "Electrical maturation trajectory of human tissues identified by
      bioelectrical impedance vector analysis".

PMID- 10896422
TI  - Asymptomatic haematuria. Scottish guidelines are different from authors
      interpretation of best available evidence.

PMID- 10896423
TI  - Asymptomatic haematuria. Nephrological screening is important.

PMID- 10896424
TI  - Asymptomatic haematuria. Oxford textbook of medicine might have helped author.

PMID- 10896425
TI  - Some people just have asymptomatic haematuria.

PMID- 10896426
TI  - Long term benefits need to be taken into account when evaluating family support
      projects.

PMID- 10896427
TI  - Organ transplantation and discrimination. Treatment should be available to
      everyone.

PMID- 10896428
TI  - Organ transplantation and discrimination. Patients with hepatitis B should not be
      given low priority.

PMID- 10896429
TI  - Midline episiotomy and anal incontinence. A prospective study is needed.

PMID- 10896430
TI  - Midline episiotomy and anal incontinence. Training is needed in the recognition
      and repair of perineal trauma.

PMID- 10896431
TI  - Midline episiotomy and anal incontinence. Results should be interpreted with
      caution in British context.

PMID- 10896433
TI  - Diagnosing and treating depression. Educating family physicians to recognise
      depression.

PMID- 10896432
TI  - Midline episiotomy and anal incontinence. Is episiotomy ethically acceptable?

PMID- 10896434
TI  - Diagnosing and treating depression. Treatment is often challenging.

PMID- 10896435
TI  - Diagnosing and treating depression. A holistic approach is recommended.

PMID- 10896436
TI  - Diagnosing and treating depression. Can primary care improve care for depressed
      patients?

PMID- 10896437
TI  - Diagnosing and treating depression. Learning to look at the illness from both
      sides.

PMID- 10896438
TI  - Managing patients with lung cancer. All evidence was considered when COIN
      guidelines were drawn up.

PMID- 10896439
TI  - Voluntary organisations already help set policy in Scotland.

PMID- 10896440
TI  - Managing patients with lung cancer. Guidelines must help bring us in line with
      European standards.

PMID- 10896441
TI  - Is norethisterone a lifestyle drug? Health is not merely the absence of disease.

PMID- 10896442
TI  - Is norethisterone a lifestyle drug? It's not a lifestyle drug in North Harrow.

PMID- 10896443
TI  - Is norethisterone a lifestyle drug? The term lifestyle is not as clear as it may
      seem.

PMID- 10896444
TI  - [Interview with a remarkable woman: Ginette Rodger].

PMID- 10896445
TI  - The core curriculum in The Netherlands.

PMID- 10896446
TI  - Haplotye analysis of Jaanese families with a superficial variant of granular
      corneal dystrohy: evidence for multiple origins of R124L mutation of
      keratoepithelin.

PMID- 10896447
TI  - Endorepair conversion.

PMID- 10896448
TI  - Aortic arch endorepair.

PMID- 10896449
TI  - Retroperitoneal haematoma.

PMID- 10896450
TI  - Re: Ruddle et al.: The morbidity of secondary vascular access. A lifetime of
      intervention.

PMID- 10896451
TI  - Re: B.S.W. Noorpuri et al.: Pseudo-aneurysm of a geniculate collateral artery
      complicating total knee replacement.

PMID- 10896452
TI  - Treatment for trigeminal neuralgia.

PMID- 10896453
TI  - Calcium-binding proteins in the mesencephalic trigeminal nucleus of the cat.

PMID- 10896454
TI  - Tribute. Gerald P. Murphy, Md, DSc (1935-2000).

PMID- 10896455
TI  - Scientists' Distinguished Awards: Orlando J. Miller, MD, and Mark I. Evans, MD.

PMID- 10896456
TI  - Ocular toxoplasmosis: new directions for clinical investigation.

PMID- 10896457
TI  - Comment on 'Posterior segment inflammation in HLA-B27+ acute anterior uveitis:
      clinical characteristics'.

PMID- 10896459
TI  - International Dental Educators' Conference. Dublin, September, 1998. Proceedings.

PMID- 10896458
TI  - 1999 International International Workshop for a Classification of Periodontal
      Diseases and Conditions. Papers. Oak Brook, Illinois, October 30-November 2,
      1999.

PMID- 10896460
TI  - Interactions with hormonal contraception.

PMID- 10896461
TI  - GP use of anti-D.

PMID- 10896462
TI  - Depo Provera--irregular bleeding management.

PMID- 10896463
TI  - Forgotten IUDS.

PMID- 10896464
TI  - Levonorgestrel IUS use in Islamic Malaysia.

PMID- 10896465
TI  - Psychological effects of sterilization in India.

PMID- 10896466
TI  - Comments on Implanon review.

PMID- 10896467
TI  - Guess what? Linear cutaneous lupus erythematous (LCLE): relationship with
      Blaschko's lines.

PMID- 10896468
TI  - Guess what? Trichlorhinophalangeal syndrome type I.

PMID- 10896469
TI  - [Prospective study of Staphylococcus aureus with reduced susceptibility to
      glycopeptides].
AB  - The emergence of clinical methicillin-resistant Staphylococcus aureus with
      reduced susceptibility to glycopeptides has recently been documented.
      Heterogeneous levels of glycopeptides susceptibility have been demonstrated in
      these isolates. Prospectively, we investigated the presence of S. aureus isolates
      with reduced susceptibility to vancomycin in our hospital from October 1997 to
      January 1998. The vancomycin and teicoplanin susceptibility of 248 consecutively
      methicillin-susceptible and -resistant S. aureus isolates from clinical and
      surveillance specimens was studied by broth microdilution and agar dilution
      methods. In addition, 108 CFU/mI of overnight cultures were plated onto BHI-agar
      plates containing 6 and 10 microg/ml of vancomycin and were incubated for 48
      hours at 35 degrees C. Under these conditions selected colonies were subcultured
      onto vancomycin plates and vancomycin susceptibility (E-test) was determined
      again. Vancomycin MIC(90) values by the agar dilution technique for methicillin
      susceptible and -resistant isolates were 2 and 4 microg/ml, respectively No
      selected colonies were observed on 10 microg/ml vancomycin plates. In contrast,
      12 isolates, including 8 (3.9%) methicillin-susceptible and 4 (9. 1%) methicillin
      resistant isolates, showed subpopulations at a frequency rate of 10(-6)-10(-7) on
      6 microg/ml vancomycin plates. Nevertheless, a significant increase in MIC values
      for vancomycin was not observed in these S. aureus subpopulations.

PMID- 10896471
TI  - Proceedings of the 3rd International Symposium on Interventional
      Electrophysiology in the Management of Cardiac Arrhythmias. Salzburg, Austria,
      September 23-26, 1998.

PMID- 10896470
TI  - [Urinary infection in brachytherapy].

PMID- 10896472
TI  - SRPrises in RNA-protein recognition.
AB  - The recent structure determination of the phylogenetically conserved cor re of
      the signal recognition particle (SRP) reveals a novel of highly un usual RNA
      protein interface, where non-canonical base pairs play a centr al role. The
      structure shows how a helix-turn-helix motif can be employ ed to bind RNA and
      offers hints as to how the signal peptide is recogniz ed by the SRP.

PMID- 10896473
TI  - The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with
      a twist.
AB  - BACKGROUND: ADP-L-glycero--mannoheptose 6-epimerase (AGME) is required for
      lipopolysaccharide (LPS) biosynthesis in most genera of pathogenic and non
      pathogenic Gram-negative bacteria. It catalyzes the interconversion of ADP-D
      glycero-D-mannoheptose and ADP-L-glycero-D-mannoheptose, a precursor of the seven
      carbon sugar L-glycero-mannoheptose (heptose). Heptose is an obligatory component
      of the LPS core domain; its absence results in a truncated LPS structure
      resulting in susceptibility to hydrophobic antibiotics. Heptose is not found in
      mammalian cells, thus its biosynthetic pathway in bacteria presents a unique
      target for the design of novel antimicrobial agents. RESULTS: The structure of
      AGME, in complex with NADP and the catalytic inhibitor ADP-glucose, has been
      determined at 2.0 A resolution by multiwavelength anomalous diffraction (MAD)
      phasing methods. AGME is a homopentameric enzyme, which crystallizes with two
      pentamers in the asymmetric unit. The location of 70 crystallographically
      independent selenium sites was a key step in the structure determination process.
      Each monomer comprises two domains: a large N-terminal domain, consisting of a
      modified seven-stranded Rossmann fold that is associated with NADP binding; and a
      smaller alpha/beta C-terminal domain involved in substrate binding. CONCLUSIONS:
      The first structure of an LPS core biosynthetic enzyme leads to an understanding
      of the mechanism of the conversion between ADP-D-glycero--mannoheptose and ADP-L
      glycero-D-mannoheptose. On the basis of its high structural similarity to UDP
      galactose epimerase and the three-dimensional positions of the conserved residues
      Ser116, Tyr140 and Lys144, AGME was classified as a member of the short-chain
      dehydrogenase/reductase (SDR) superfamily. This study should prove useful in the
      design of mechanistic and structure-based inhibitors of the AGME catalyzed
      reaction.

PMID- 10896474
TI  - Proceedings of the 15th Congress of the Italian Society of Nephrology, Triveneto
      Section. Padova, Italy, September 17, 1999.

PMID- 10896475
TI  - Air injection during FNA-ultrasound and mammographic appearances.

PMID- 10896476
TI  - The ultrasonic Barberpole: midgut volvulus and malrotation in a young adult.

PMID- 10896477
TI  - Giant myelolipoma of the adrenal gland: natural history.

PMID- 10896478
TI  - Adrenaline in reactions to intravenous contrast medium.

PMID- 10896480
TI  - Medicaid managed care in Maryland.

PMID- 10896479
TI  - Unenhanced helical CT for renal colic--is the radiation dose justifiable?

PMID- 10896481
TI  - Current opinion in the treatment of community-acquired pneumonia: results of the
      presymposium interactive question and answer session.

PMID- 10896482
TI  - Consensus among participants for the treatment of community-acquired pneumonia:
      results of the postsymposium interactive question and answer session.

PMID- 10896484
TI  - Reported channel formation by prion protein fragment 106-126 in planar lipid
      bilayers cannot be reproduced.

PMID- 10896483
TI  - The disulphide bond arrangement in the major pepsin inhibitor PI-3 of Ascaris
      suum.

PMID- 10896485
TI  - Advances in Transfusion Safety. Proceedings of a symposium. San Francisco, USA.
      March 18-20, 1999.

PMID- 10896486
TI  - Comparison of endoscopic ligation and propranolol for the primary prevention of
      variceal bleeding.

PMID- 10896487
TI  - A prospective randomized trial of Teflon versus polyethylene stents for distal
      malignant biliary obstruction.

PMID- 10896488
TI  - A blind comparison of the effectiveness of endoscopic ultrasonography and
      endoscopy in staging early gastric cancer.

PMID- 10896489
TI  - In the beginning.

PMID- 10896490
TI  - Telepsychiatry for the management of a liver transplantation candidate in the
      primary care setting.

PMID- 10896491
TI  - When consultants write orders: physicians' attitudes, beliefs, and practices.

PMID- 10896492
TI  - Clinical significance of pseudohallucinations.

PMID- 10896493
TI  - Neuropsychiatric sequelae in a case of St. Louis encephalitis.

PMID- 10896494
TI  - Comorbidity of keratosis follicularis (Darier's Disease) and bipolar affective
      disorder: an indication for valproate instead of lithium.

PMID- 10896495
TI  - Delusional parasitosis following occipito-temporal cerebral infarction.

PMID- 10896496
TI  - The usefulness of single photon emission computed tomography in Charles Bonnet
      syndrome: a case with occipital lobe involvement.

PMID- 10896497
TI  - Musical hallucinations with post-pharyngolaryngoesophagectomy aphonia.

PMID- 10896499
TI  - [Proceedings of the Polish-German Interdisciplinary Symposium: Ethics in
      Medicine. Cracow, 15-17 October 1998].

PMID- 10896498
TI  - Do consultation-liaison services change the behavior of primary care providers? A
      review.

PMID- 10896500
TI  - Publication of population data of human polymorphisms.

PMID- 10896502
TI  - Charley Steinberg 1932-1999.

PMID- 10896501
TI  - Traumatic subarachnoid haemorrhage: a 10-year case study and review.

PMID- 10896503
TI  - AIDS and school children.

PMID- 10896504
TI  - Form and function: the integration of physics and biology.

PMID- 10896505
TI  - The paradox of size and the role of surgery in cancer of the uterine cervix: are
      we doing the correct surgery?

PMID- 10896506
TI  - In regard to Dr. Kondziolka et al.: stereotactic radiosurgery plus whole brain
      radiotherapy alone for patients with multiple brain metastases.

PMID- 10896507
TI  - West Nile virus survives winter; no surprise, says CDC.

PMID- 10896509
TI  - Doing cell science.

PMID- 10896510
TI  - From null hypothesis to clinical significance.

PMID- 10896508
TI  - Tn551-mediated insertional inactivation of the fmtB gene encoding a cell wall
      associated protein abolishes methicillin resistance in Staphylococcus aureus.
AB  - A Tn551 insert in a gene termed fmtB was shown to reduce oxacillin as well as
      Triton X-100 resistance in highly methicillin-resistant Staphylococcus aureus
      (MRSA) COL. Backcrosses of fmtB::Tn551 into S. aureus COL and into two
      genetically distinct MRSA strains, KSA8 and NCTC10443, confirmed the linkage of
      fmtB::Tn551 with loss of oxacillin resistance. The fmtB gene codes for a protein
      of a deduced molecular mass of 263 kDa that contains 17 tandem repeats of 75
      amino acids and a C-terminal LPXTG cell wall-sorting motif. Immunoblots with anti
      FmtB antibodies confirmed its localization in the cell wall fraction. The fmtB
      gene was mapped downstream of the phosphoglucosamine mutase operon glmM which
      catalyses formation of glucosamine-1-phosphate. Oxacillin resistance was not
      restored in fmtB mutants by trans-complementation with fmtB. However, although
      GlmM production was not affected by fmtB inactivation, oxacillin resistance was
      increased in fmtB mutants by introducing a plasmid-borne glmM gene, presumably by
      GlmM overexpression. Interestingly, a similar phenotypic complementation was
      obtained in fmtB mutants by including substrate level concentrations of N
      acetylglucosamine or glucosamine in the growth medium. Inactivation of the fmtB
      gene seems therefore to have an indirect effect on methicillin resistance which
      can be relieved by increasing the production of the cell wall precursor
      glucosamine-1-phosphate.

PMID- 10896511
TI  - The Severe Cognitive Impairment Profile (SCIP).

PMID- 10896512
TI  - Nutrition and you: trends 2000. ADA's Public Relations Team.

PMID- 10896513
TI  - Patient-reported urinary continence and sexual function after anatomic radical
      prostatectomy.

PMID- 10896514
TI  - Immediate hormonal therapy compared with observation after radical prostatectomy
      and pelvic lymphadenectomy in men with node-positive prostate cancer.

PMID- 10896515
TI  - Minimum incidence and diagnostic rate of first urinary tract infection.

PMID- 10896516
TI  - 45,X/46,XY mosaicism: report of 27 cases.

PMID- 10896517
TI  - Acute scrotal pain in children: results of 543 surgical explorations.

PMID- 10896518
TI  - Experimental gestational pyelonephritis induces preterm births and low birth
      weights in C3H/HeJ mice.

PMID- 10896519
TI  - The AIDS epidemic--considerations for the 21st century.

PMID- 10896520
TI  - From the Food and Drug Administration.

PMID- 10896521
TI  - From the Centers for Disease Control and Prevention. Update: Influenza activity-
      United States, and worldwide, 1999-2000 season, and composition of the 2000-2001
      influenza vaccine.

PMID- 10896522
TI  - From the Centers for Disease Control and Prevention. Health-related quality of
      life among adults with arthritis--Behavioral Risk Factor Surveillance System, 11
      states, 1996-1998.

PMID- 10896524
TI  - JAMA Patient Page. Psychiatric illness in older adults.

PMID- 10896523
TI  - From the Centers for Disease Control and Prevention. Progress toward
      poliomyelitis eradication--Democratic Republic of Congo, 1996-1999.

PMID- 10896525
TI  - From the Centers for Disease Control and Prevention. Entry into prenatal care-
      United States, 1989-1997.

PMID- 10896526
TI  - From the Centers for Disease Control and Prevention. Palmar pallor as an
      indicator for anthelminthic treatment among ill children aged 2-4 years--western
      Kenya, 1998.

PMID- 10896527
TI  - From the Centers for Disease Control and Prevention. Scombroid fish poisoning-
      Pennsylvania, 1998.

PMID- 10896528
TI  - From the Centers for Disease Control and Prevention. Neural tube defect
      surveillance and folic acid intervention--Texas-Mexico border, 1993-1998.

PMID- 10896529
TI  - JAMA Patient Page. The benefits of regular physical activity.

PMID- 10896530
TI  - From the Health Care Financing Administration. Evaluation and management services
      guideline.

PMID- 10896531
TI  - From the Centers for Disease Control and Prevention. Surveillance for possible
      estuary-associated syndrome--six states, 1998-1999.

PMID- 10896532
TI  - From the Centers for Disease Control and Prevention. Alcohol policy and sexually
      transmitted disease rates--United States, 1981-1995.

PMID- 10896533
TI  - From the Centers for Disease Control and Prevention. Prevalence of leisure-time
      and occupational physical activity among employed adults--United States, 1990.

PMID- 10896534
TI  - From the Centers for Disease Control and Prevention. Public health aspects of the
      Rainbow Family of Living Light annual gathering--Allegheny National Forest,
      Pennsylvania, 1999.

PMID- 10896535
TI  - JAMA Patient Page. Generalized anxiety disorder.

PMID- 10896536
TI  - [Survey of anesthesia-related incidents in Japan during 1998].

PMID- 10896537
TI  - [Case of pulmonary aspergillosis successfully treated with itraconazole].

PMID- 10896538
TI  - [Therapy of deep seated mycoses--Timing of administration and selection of
      antifungal agents].

PMID- 10896539
TI  - [Two cases of pulmonary aspergillosis treated with itraconazole following
      pneumonectomy].

PMID- 10896540
TI  - [Two cases of pulmonary aspergillosis successfully treated with multidrug
      therapy].

PMID- 10896541
TI  - [Four cases of pulmonary aspergilloma successfully treated with drug therapy].

PMID- 10896542
TI  - Proceedings of the ECETOC - EEMS Symposium on Dose-Response and Threshold
      Mediated Mechanisms in Mutagenesis. Salzburg, Austria, 7 September 1998.

PMID- 10896543
TI  - Effect of ramipril on cardiovascular events in high-risk patients.

PMID- 10896544
TI  - Effect of ramipril on cardiovascular events in high-risk patients.

PMID- 10896545
TI  - Effect of ramipril on cardiovascular events in high-risk patients.

PMID- 10896546
TI  - Effect of ramipril on cardiovascular events in high-risk patients.

PMID- 10896547
TI  - Noninvasive diagnosis of fetal anemia by Doppler ultrasonography.

PMID- 10896548
TI  - Noninvasive diagnosis of fetal anemia by Doppler ultrasonography.

PMID- 10896549
TI  - Implantable cardioverter-defibrillators in hypertrophic cardiomyopathy.

PMID- 10896550
TI  - Tinea incognito misdiagnosed as erythema migrans.

PMID- 10896551
TI  - Atopy and a mutation in the interleukin-4 receptor gene.

PMID- 10896552
TI  - Case 3-2000.

PMID- 10896553
TI  - More on virostatic therapy for advanced lymphoproliferation associated with
      Epstein-Barr virus in an HIV-infected patient.

PMID- 10896554
TI  - Inhibition of megakaryopoiesis by Kell-related antibodies.

PMID- 10896555
TI  - Disclosure of authors' conflicts of interest--a follow-up.

PMID- 10896556
TI  - Disclosure of authors' conflicts of interest--a follow-up.

PMID- 10896557
TI  - Disclosure of authors' conflicts of interest--a follow-up.

PMID- 10896558
TI  - Exercise and coronary endothelial function.

PMID- 10896559
TI  - Angiogenesis factors in acute myocardial ischemia and infarction.

PMID- 10896560
TI  - Fistula between the left internal thoracic artery and the coronary sinus.

PMID- 10896561
TI  - Physician-assisted suicide and euthanasia.

PMID- 10896562
TI  - Physician-assisted suicide and euthanasia.

PMID- 10896563
TI  - Physician-assisted suicide and euthanasia.

PMID- 10896564
TI  - Physician-assisted suicide and euthanasia.

PMID- 10896565
TI  - Physician-assisted suicide and euthanasia.

PMID- 10896566
TI  - High serum potassium concentrations after recentrifugation of stored blood
      specimens.

PMID- 10896567
TI  - Fungal get-together.

PMID- 10896568
TI  - [Exemplary conduct of teaching physicians is a big part of problem-oriented
      learning].

PMID- 10896570
TI  - [Pericardial effusion as presentation form of giant cell arteritis].

PMID- 10896569
TI  - Special issue: Festschrift in honor of Dr. Morris Pollard.

PMID- 10896571
TI  - Rheumatoid factors and Chagas' disease.

PMID- 10896572
TI  - Scientific misconduct. Panel finds scores of suspect papers in German fraud
      probe.
AB  - A new report paints a darker picture of what may be the highest profile case of
      scientific fraud in postwar Germany. After a 2-year investigation of all 347
      scientific articles co-authored by former hematologist and cancer researcher
      Friedhelm Herrmann, a task force jointly sponsored by Germany's main granting
      agency, the DFG, and the country's largest cancer charity released a report on 19
      June indicating that the scope of the fraud--first uncovered 3 years ago--is far
      more extensive than previously thought. Although Herrmann and a co-author have
      left their academic posts, the new revelations could place other careers in
      jeopardy.

PMID- 10896573
TI  - Neurobiology. Death leads to brain neuron birth.
AB  - Although scientists have provided mounting evidence in the past few years that
      new neurons can be produced in some areas of the adult brain, the neocortex--the
      region most concerned with such higher brain functions as memory and learning-
      did not seem capable of such regeneration. Now, in the 22 June issue of Nature,
      neuroscientists report that when they induced certain neurons in the neocortex of
      adult mice to self-destruct, the loss triggered the formation of replacement
      neurons by brain stem cells. If similar regeneration of brain neurons can be
      triggered in humans, the findings could open the door for treatments that might
      restore memory in Alzheimer's disease, for example, or undo the damage wreaked by
      spinal cord injury.

PMID- 10896574
TI  - European science policy. France rebels against gene-patenting law.

PMID- 10896575
TI  - Research policy. Report tracks federal funding in each state.

PMID- 10896576
TI  - Neuroscience. A critical issue for the brain.
AB  - The notion that there is a "critical period" for learning in the first 3 years of
      life has cropped up widely in media reports recently. But although critical
      periods have been well documented for the development of sensory systems in the
      brain, especially vision, researchers differ over whether they exist for the
      development of the brain functions that underlie complex learning and thinking
      skills. Scientists do agree, however, that where critical periods do exist, they
      are not sharply defined, nor are they unique to the first 3 years of life, as has
      been conveyed in the media. The message should give hope to adults who may not
      learn with the ease of early childhood, but can still do it.

PMID- 10896577
TI  - Society for Developmental Biology meeting. A mile-high view of development.
AB  - BOULDER, COLORADO--Nearly 600 scientists gathered at the base of the Flatirons to
      discuss the growth and patterning of organisms including plants, worms, fruit
      flies, fish, and mice at the 59th annual meeting of the Society for Developmental
      Biology. Among the highlights were clues about how blind cave fish lost their
      eyes and how a gene that influences cell movement might help cancer spread.

PMID- 10896578
TI  - Paleontology. Feathers, or flight of fancy?
AB  - On page 2202, researchers describe the 220-million-year-old Longisquama insignis,
      a squat, mouse-sized reptile with at least six vanelike appendages up to 12
      centimeters long sprouting from its spine. The authors argue that the appendages
      are feathers much like those of modern birds; outside the paper, they have touted
      the fossil as "an ideal bird ancestor." That conclusion has infuriated
      paleontologists--not just because it challenges the prevalent theory that birds
      evolved from theropod dinosaurs, but because they say it does so in an
      unscientific way.

PMID- 10896579
TI  - Globalization, ethics, and AIDS vaccines.

PMID- 10896580
TI  - Contributions to the U.S. space program.

PMID- 10896581
TI  - Health care in former Soviet republics.

PMID- 10896582
TI  - Mbeki and AIDS in Africa.

PMID- 10896583
TI  - Many modes of movement.

PMID- 10896584
TI  - Many modes of movement.

PMID- 10896585
TI  - Many modes of movement.

PMID- 10896586
TI  - A chicken in every pot, thanks to sulfonamide drugs.

PMID- 10896587
TI  - China's forest policy for the 21st century.
AB  - A half-century policy of forest exploitation and monoculture in China has led to
      disastrous consequences, including degradation of forests and landscapes, loss of
      biodiversity, unacceptable levels of soil erosion, and catastrophic flooding. A
      new forest policy had been adopted in China called the Natural Forest
      conservation Program (NFCP), which emphasizes expansion of natural forests and
      increasing the productivity of forest plantations. Through locally focused
      management strategies, biodiversity and forest resources will be sustained, and
      downstream regions will be better protected from flooding. This new policy is
      being implemented with a new combination of policy tools, including technical
      training and education, land management planning, mandatory conversion of
      marginal farmlands to forest, resettlement and retaining of forest dwellers,
      share in private ownership, and expanded research. These policy tools may have
      wider relevance for other countries, particularly developing countries.

PMID- 10896588
TI  - Molecular biology. Telomeres keep on rappin'.
AB  - Many molecules help maintain the ends of chromosomes, which get chewed off as
      cells age. Lundblad in her provocative Perspective now tells us about another
      protein, hRap1, that regulates the length of telomeres in human cells with the
      help of the TRF proteins. The homology between hRap1 and its counterpart in yeast
      suggests how the complex molecular machinery needed to maintain chromosome ends
      may have evolved.

PMID- 10896589
TI  - Development. A degrading way to make an organ.
AB  - Working out how organs form during embryonic development is a fascinating area of
      research. In a witty Perspective, Jeff Hardin describes new findings (Nishiwaki
      et al.) that reveal the many intricate steps needed for gonads to form in the
      worm C. elegans. Two key players, GON-1 and MIG-17, are metalloproteases that may
      help migration of distal tip cells by degrading extracellular matrix components.

PMID- 10896591
TI  - HIV and Africa's future.

PMID- 10896590
TI  - Molecular biology. Mothers setting boundaries.
AB  - Certain genes are only expressed at one allele, a phenomenon called imprinting.
      Although it is well established that one allele of certain imprinted genes is
      silenced through methylation, this does not appear to be the case for all
      imprinted genes. In a thoughtful Perspective, Thorvaldsen and Bartolomei discuss
      new findings showing that insertion of insulator elements (boundary regions)
      between the promoter of a gene and its enhancer (a sequence that boosts gene
      expression) may be another way in which genes are silenced during imprinting.

PMID- 10896592
TI  - Ground zero: AIDS research in Africa.
AB  - More and more European and North American AIDS researchers are coming to sub
      Saharan Africa, which is home to a whopping 70% of all HIV-infected people. These
      investigators are collaborating with local researchers on projects that aim to
      slow both HIV's spread and the course of disease in the millions already
      infected. But most African countries--constrained by limited resources, weak
      infrastructures, social mores, and political inaction--have grave difficulties
      translating research insights into prevention and treatment strategies.

PMID- 10896593
TI  - Is AIDS in Africa a distinct disease?
AB  - In Africa, opportunistic infections, transmission patterns, and viral subtypes
      differ from what is seen in the AIDS epidemics of the United States and Europe,
      yet 2 decades into the epidemic, AIDS researchers have only a shaky handle on the
      fundamental question: What accounts for these differences? The answers have
      potentially important implications for both prevention and treatment strategies.

PMID- 10896594
TI  - Balancing the collaboration equation.
AB  - Most African countries can't afford to support much research themselves, so the
      vast majority of studies of HIV/AIDS are being conducted in collaboration with
      scientists from the developed world. These partnerships have brought major
      benefits, but inherent inequalities can cause tensions and require constant give
      and-take from both sides. An inside look at three veteran marriages between
      African AIDS researchers and foreign colleagues illustrates the benefits--and
      stresses--of partnership.

PMID- 10896595
TI  - Major international AIDS research collaborations.
AB  - Science lists the major collaborative research projects throughout sub-Saharan
      Africa. This list will be updated periodically at
      www.sciencemag.org/feature/data/africacollaborations.shl. Please send additions
      and changes to science_news@aaas.org.

PMID- 10896596
TI  - Profile: building a world-class lab from scratch.
AB  - In 1996, Projet RETRO-CI, a U.S.-Ivoirian collaboration funded by the U.S.
      Centers for Disease Control and Prevention, hired virologist John Nkengasong to
      build a virology lab from scratch. Now Nkengasong runs one of the best equipped
      HIV labs in sub-Saharan Africa and has published dozens of papers helping to
      clarify properties of specific strains of the virus.

PMID- 10896597
TI  - Profile: restarting Rwanda's research engine.
AB  - When ethnic tensions between Rwanda's Hutus and Tutsis erupted in April 1994, one
      of Africa's most vibrant scientific communities suddenly vanished. Now molecular
      biologist Etienne Karita has returned to head the Belgian-funded National
      Reference Laboratory for Retroviral Infections.

PMID- 10896598
TI  - Profile. The risks--and rewards--of war zone research.
AB  - Gulu, about 4 hours north of here by car, is in an "upcountry" region torn by
      armed conflict. So upcountry clinical researchers like Matthew Lukwiya, a native
      of the Gulu district, play a critical role--and win high praise from their
      colleagues.

PMID- 10896599
TI  - The mother of all HIV challenges.
AB  - AIDS researchers are finding cheaper and simpler ways to slow the spread of HIV
      from mother to child, and more pregnant women, even in the poorest countries,
      have access to anti-HIV drugs and formula--thanks to the largesse of donors,
      discounts from industry, new trade laws, and the tenacity of individual
      clinicians. But just as researchers offer ways to clear one enormous hurdle--drug
      availability--they run smack into other ones, ranging from social stigmas that
      discourage testing to disinterest on the part of cash-strapped health authorities
      to a deeply ingrained culture of breast-feeding--often supported by government
      policy for otherwise sound health reasons.

PMID- 10896600
TI  - Profile. Preventing infections with today's tools.
AB  - With no vaccine in sight powerful enough to halt the spread of HIV, Africa is
      left with one strategy to combat the epidemic: prevention. The University of
      Manitoba's Frank Plummer, who oversees a large research collaboration in Nairobi,
      Kenya, says his group has identified a half-dozen effective interventions to
      lower HIV transmission rates, but "the scale at which they're implemented is
      tiny."

PMID- 10896602
TI  - Profile: McIntyre and Gray have a will and a way.
AB  - At the Chris Hani Baragwanath Hospital here, where HIV infects more than 20% of
      the 17,000 pregnant women who give birth here each year, pediatrician Glenda Gray
      and obstetrician James McIntyre aggressively try to help HIV-infected pregnant
      women stop the virus from infecting their babies.

PMID- 10896601
TI  - Profile. An ambassador of research.
AB  - Elizabeth Ngugi, a nurse and social worker with a collaborative AIDS research
      program based at the University of Nairobi, plays a role that is crucial for many
      AIDS projects throughout Africa--but one that seldom receives credit in
      scientific circles. Like an ambassador of research, Ngugi connects ostracized
      communities that have little education and even less money to an international
      team of AIDS scientists.

PMID- 10896603
TI  - Searching for the epidemic's origins.
AB  - Theories about the origin of AIDS all suffer from a dearth of data. For more than
      a decade, researchers have recognized the close genetic links between SIV from
      sooty mangabeys and HIV-2, a type of the virus that is mostly confined to west
      African countries, but to date, there are scant data that closely link HIV-1, the
      predominant human AIDS virus, to SIVs found in primates.

PMID- 10896604
TI  - Africa boosts AIDS vaccine R&D.
AB  - Efforts have recently heated up in several African countries to tailor-make
      preparations that many believe offer the best hope yet for stopping HIV cold. But
      all are at the earliest stages, which means it will take years before a vaccine
      might prove its worth.

PMID- 10896605
TI  - Profile: a native son comes home to help.
AB  - In December 1996, Omu Anzala returned to Kenya after completing his Ph.D. work in
      Canada on HIV's interactions with the immune system to work with a collaborative
      AIDS research project started by researchers from his university and the
      University of Manitoba. Now the International AIDS Vaccine Initiative has funded
      Anzala and his collaborators to fashion an AIDS vaccine based on a strain of HIV
      circulating in Kenya.

PMID- 10896606
TI  - South Africa's new enemy.
AB  - Many South Africans long dreamed of the day when the oppressive apartheid system
      would end. That day has come, but now the country faces a new disaster: one of
      the world's worst HIV epidemics--and most confusing government responses.

PMID- 10896607
TI  - Profile: a research renaissance, South African style.
AB  - Shortly after the news broke this winter that President Thabo Mbeki had doubts
      about the link between HIV and AIDS, Malegapuru William Makgoba, the first black
      president of South Africa's Medical Research Council, launched a high-profile,
      frontal assault, including sharply worded editorials in leading South African
      newspapers and in Science. It's not a particularly comfortable position for a man
      who shares many of Mbeki's political views.

PMID- 10896608
TI  - Confronting conference complexities.
AB  - Next month, Hoosen "Jerry" Coovadia will chair the XIII International AIDS
      Conference here, the first time this high-profile gathering has been held in a
      developing country. Coovadia and the other organizers have gone to great lengths
      to make the conference work smoothly. Photos by Malcolm Linton

PMID- 10896609
TI  - Improved identification of axonal shear injuries with gradient echo MR technique.

PMID- 10896610
TI  - Asthma care.

PMID- 10896611
TI  - Ultrasound placement of peripherally inserted central catheters (PICCs) in adults
      with cystic fibrosis.

PMID- 10896612
TI  - Screening for polymorphisms in exon 5 of the glutathione S-transferase P1 gene.

PMID- 10896613
TI  - [A possible approach to improve present meat inspection].
AB  - The final decision in the meat inspection mainly depends on the results of the
      examinations before, during, or directly after the slaughter of animals in the
      slaughterhouse. The present threats to public health cannot be adequately judged
      on that place and under these circumstances. A new approach of the meat
      inspection methods is only possible with the cooperation of the other EU member
      states and the people who are involved in the meat inspection. New views on the
      purpose of meat inspection and the possibility of translation of these ideas
      towards Food Safety Objectives could be the basis for adaptation of the meat
      inspection. The rigid form in which the present meat inspection exists can be
      changed by this approach.

PMID- 10896614
TI  - [Mink breeders provoke discussion. The beginning of the end].

PMID- 10896615
TI  - [Accidental poisoning by commercial cat and dog food].

PMID- 10896616
TI  - [Classic swine fever epidemic in the Netherlands 1997-1998].

PMID- 10896617
TI  - [Large grazers in the Dutch wetland "de Oostvaardersplassen." Reaction to the
      "Guide to Large Grazers" of the State Secretary for Agriculture, Nature
      Management and Fisheries].
AB  - The recently published 'Guidelines large herbivores'from the Secretary of State
      Agriculture, Nature Management and Fisheries are commented upon. These Guidelines
      pay insufficient attention to the welfare of the animals used. Only the
      management of domestic animals is discussed while the management of the deer,
      which form an integral part of the system is left open. The name of the
      Veterinary Guidance Committee Nature is questioned since it suggest an
      independent contribution of specialised veterinary knowledge on the various
      health and welfare issues, but in reality a broad representation of different
      governmental and public organizations is present. The view points of this so
      called veterinary committee seem to disagree with those of the Dutch veterinary
      community as formulated by the Royal Netherlands Veterinary Association.
      Independent of the species of animals used for the management of the area a plea
      is held for active control of the population - 'looking through the eyes of the
      wolve' - to dampen large fluctuations in population size and prevent unnecessary
      suffering through starvation. Since the domesticated animals used to have to
      comply with the strict veterinary regulations when intended for human consumption
      the suggestion is made to investigate the the possibility of using only truly
      wild animals like deer, European bison and wild boar for the management of the
      wetland. When wild animals are used culled animals can be used for human
      consumption and this prevents that every year numerous cadavers of cattle and
      horse have to be collected from the area and incinerated.

PMID- 10896618
TI  - [Veterinary specialization: a strong persevering development in at home and
      abroad].

PMID- 10896619
TI  - Special issue dedicated to the memory of W.M. Stobbs.

PMID- 10896620
TI  - Animal influenza viruses. Proceedings of a symposium. Ghent, Belgium. May 16-18,
      1999.

PMID- 10896621
TI  - Immunosurveillance on Kosovar children refugees in Southern Italy.

PMID- 10896622
TI  - Elevated lipoprotein(a) with statin therapy.

PMID- 10896623
TI  - Chronic fatigue syndrome: the fundamentals still apply.

PMID- 10896624
TI  - Isolated relapse of acute lymphoblastic leukemia in the breast masquerading as
      gynecomastia.

PMID- 10896625
TI  - Scedosporum prolificans infection: an unusual cause of cerebral infarct.

PMID- 10896626
TI  - Distinguishing fulminant perineal necrosis as a result of Wegener's
      granulomatosis from Fournier's gangrene.

PMID- 10896627
TI  - Colonic late-onset familial adenomatous polyposis combined with severe duodenal
      polyposis and familial endometrial cancer.

PMID- 10896628
TI  - Medication bezoar and esophagitis in a patient with HIV infection receiving
      combination antiretroviral therapy.

PMID- 10896629
TI  - Decolonization of methicillin-resistant Staphylococcus aureus by disinfection of
      the skin.

PMID- 10896630
TI  - Hypermagnesemia-induced multiorgan failure.

PMID- 10896631
TI  - Q fever and antineutrophil cytoplasmic antibodies.

PMID- 10896632
TI  - YKL-40 and graft rejection.

PMID- 10896633
TI  - Gabapentin therapy for diabetic neuropathic pain.

PMID- 10896634
TI  - Prevention of ventilator-associated pneumonia.

PMID- 10896635
TI  - Anaesthesia for organ donation in the brainstem dead.

PMID- 10896636
TI  - Salary equity among male and female internists in Pennsylvania.
AB  - BACKGROUND: Women constitute an increasing proportion of physicians in the United
      States. Historically, inequities have existed between male and female physicians
      in professional advancement, but evidence has suggested that disparities in
      salary are resolving. OBJECTIVE: To examine the current state of salary equity
      among male and female internists. DESIGN: Population-based survey mailed to all
      Board-certified female internists and a matched group of male internists who had
      graduated from medical school 10 to 30 years ago and were currently practicing.
      SETTING: Pennsylvania. PARTICIPANTS: 232 male and 213 female internists for whom
      data were complete. MEASUREMENTS: Respondents answered questions about
      demographic characteristics, training, practice type and setting, status within
      the practice, family life, and salary. RESULTS: Women were more likely to be
      involved in the least lucrative practice arrangements. They were more likely to
      be in low-paying specialties, to not be a partner in the practice, and to be
      salaried employees; they also spent fewer hours per week seeing patients. Even
      after adjustment for these differences, hourly earnings were significantly higher
      (14%) among men than among their female colleagues. Men's earnings significantly
      exceeded women's earnings among physicians with no academic affiliation, those in
      high-earning specialties, and those in general internal medicine. CONCLUSIONS:
      Significant salary differentials exist between male and female internists overall
      and in various medical practice settings.

PMID- 10896637
TI  - Effects of growth hormone administration on inflammatory and other cardiovascular
      risk markers in men with growth hormone deficiency. A randomized, controlled
      clinical trial.
AB  - BACKGROUND: Growth hormone-deficient adults have increased cardiovascular
      mortality. Growth hormone replacement may affect cardiovascular risk.
      Inflammation plays an important role in atherosclerosis, and inflammatory markers
      are predictive of cardiovascular events. OBJECTIVE: To investigate the effect of
      growth hormone replacement on inflammatory and other cardiovascular risk factors.
      DESIGN: Randomized, single-blind, placebo-controlled trial. PATIENTS: 40 men with
      adult-onset growth hormone deficiency. INTERVENTION: Growth hormone or placebo
      given for 18 months at a dose adjusted for normal serum insulin-like growth
      factor I level. MEASUREMENTS: Anthropometric, hemoglobin A1c, and central fat
      values were assessed every 6 months. Levels of glucose, insulin, insulin-like
      growth factor I, and lipids were measured at 1, 3, 6, 12, and 18 months. C
      reactive protein, serum amyloid polypeptide A, inteleukin-6, and lipoprotein(a)
      levels were determined at baseline and 6 and 18 months. RESULTS: C-reactive
      protein and inteleukin-6 levels decreased in growth hormone recipients compared
      with placebo recipients (differences between groups, -1.9 +/- 0.6 mg/L [P =
      0.0027] and -1.3 +/- 0.5 ng/L [P = 0.013], respectively). Changes in serum
      amyloid polypeptide A levels between groups did not reach statistical
      significance (difference between groups, -2.4 +/- 1.2 mg/L; P = 0.056). Serum
      cholesterol levels, low-density lipoprotein cholesterol levels, and ratios of
      total cholesterol to high-density lipoprotein cholesterol decreased in growth
      hormone recipients in the first 3 months compared with placebo recipients
      (differences between groups, -0.86 +/- 0.17 mmol/L [-33.2 +/- 6.6 mg/dL] [P <
      0.001], -0.63 +/- 0.20 mmol/L [-24.5 +/- 5.9 mg/dL] [P < 0.001], and -0.56 +/-
      0.26 [P = 0.040], respectively), but the decrease was not maintained from month 6
      to month 18. Lipoprotein(a) levels increased (difference between groups, 22.0 +/-
      8.0 mg/L; P = 0.0096). Short-term increases occurred in glucose levels, insulin
      levels, and insulin-to-glucose ratios (differences between groups, 0.54 +/- 0.16
      mmol/L [9.6 +/- 2.8 mg/dL] [P = 0.0018], 37.9 +/- 9.6 pmol/L [P < 0.001], and 6.0
      +/- 1.8 [P = 0.0025], respectively), but only the increase in glucose level was
      maintained over the long term (difference between groups, 0.56 +/- 0.17 mmol/L
      [10.0 +/- 3.1 mg/dL]; P = 0.0026). Hemoglobin A1c values did not change. Truncal
      fat-to-total fat ratios decreased (difference between groups, -0.018 +/- 0.007; P
      = 0.0087). CONCLUSIONS: Long-term growth hormone replacement in men reduces
      levels of inflammatory cardiovascular risk markers, decreases central fat, and
      increases lipoprotein(a) and glucose levels without affecting lipid levels.

PMID- 10896638
TI  - Body size and risk for clinical fractures in older women. Study of Osteoporotic
      Fractures Research Group.
AB  - BACKGROUND: Small body size predicts hip fractures in older women. OBJECTIVE: To
      test the hypothesis that small body size predicts the risk for other clinical
      fractures. DESIGN: Prospective cohort study. SETTING: Population-based listings
      in four areas of the United States. PATIENTS: 8059 ambulatory nonblack women 65
      years of age or older. MEASUREMENTS: Weight, weight change since 25 years of age,
      body mass index, lean body mass and percent body fat, and nonspine fractures
      during 6.4 years of follow-up. RESULTS: Compared with women in the highest
      quartile of weight, women in the lowest quartile had relative risks of 2.0 (95%
      CI, 1.5 to 2.8) for hip fractures, 2.3 (CI, 1.1 to 4.7) for pelvis fractures, and
      2.4 (CI, 1.5 to 3.9) for rib fractures. Adjustment for total-hip bone mineral
      density eliminated the elevated risk. Results were similar for other body size
      measures. Smaller body size was not a risk factor for humerus, elbow, wrist
      ankle, or foot fractures. CONCLUSIONS: Total body weight is useful in the
      prediction of hip, pelvis, and rib fractures when bone mineral density has not
      been measured.

PMID- 10896639
TI  - Cultural and economic factors that (mis)shape antibiotic use: the
      nonpharmacologic basis of therapeutics.
AB  - The use of antibiotics in both ambulatory and inpatient settings is heavily
      shaped by cultural and economic factors as well as by microbiological
      considerations. These nonpharmacologic factors are relevant to clinicians and
      policymakers because of the clinical and fiscal toll of inappropriate antibiotic
      prescribing, including excessive use, preventable adverse effects, and the
      increasing prevalence of resistant organisms. An understanding of the
      determinants of antibiotic consumption is critical to explain current patterns of
      use and to devise programs to reduce inappropriate use. Patient motivations
      include the desire for a tangible product of the clinical encounter coupled with
      incorrect perceptions of the effectiveness of antibiotics, particularly in viral
      infections. Physician behavior can be explained by such factors as lack of
      information, a desire to satisfy patient demand, and pressure from managed care
      organizations to speed throughput. Marketing campaigns directed at both
      physicians and patients further serve to increase demand, especially for newer,
      costlier products. Studies of antibiotic use patterns in inpatient and outpatient
      care consistently demonstrate considerable inappropriate prescribing, which is
      likely to exacerbate the emergence of resistant organisms. Several approaches
      have been shown to improve the rationality of antibiotic use. Computer-based
      algorithms or reminders can prompt physicians to improve antibiotic choices at
      the time of prescribing; paper-based order entry forms can achieve the same goal.
      Interactive educational outreach ("academic detailing") is a practical
      implementation of social marketing principles to improve antibiotic use. Public
      education programs directed at consumers can help to reduce the inappropriate
      patient demand that helps to drive much improper antibiotic prescribing.

PMID- 10896640
TI  - Pharmacologic treatment of the irritable bowel syndrome: a systematic review of
      randomized, controlled trials.
AB  - PURPOSE: To evaluate the efficacy of pharmacologic agents for the irritable bowel
      syndrome. DATA SOURCES: Electronic literature search of MEDLINE (1966 to 1999),
      EMBASE (1980 to 1999), PsycINFO (1967 to 1999), and the Cochrane controlled
      trials registry and a manual search of references from bibliographies of
      identified articles. STUDY SELECTION: Randomized, double-blind, placebo
      controlled, parallel, or crossover trials of a pharmacologic intervention for
      adult patients that reported outcomes of improvement in global or irritable bowel
      specific symptoms. DATA EXTRACTION: Qualitative and quantitative data reported on
      study groups, interventions, treatment outcomes, and trial methodologic
      characteristics. DATA SYNTHESIS: 70 studies met the inclusion criteria. The most
      common medication classes were smooth-muscle relaxants (16 trials), bulking
      agents (13 trials), prokinetic agents (6 trials), psychotropic agents (7 trials),
      and loperamide (4 trials). The strongest evidence for efficacy was shown for
      smooth-muscle relaxants in patients with abdominal pain as the predominant
      symptom. Loperamide seems to reduce diarrhea but does not relieve abdominal pain.
      Although psychotropic agents were shown to produce global improvement, the
      evidence is based on a small number of studies of suboptimal quality.
      Psychotropic drugs, 5-hydroxytryptamine (5-HT)-receptor antagonists, peppermint
      oil, and Chinese herbal medicine require further study. CONCLUSIONS: Smooth
      muscle relaxants are beneficial when abdominal pain is the predominant symptom.
      In contrast, the efficacy of bulking agents has not been established. Loperamide
      is effective for diarrhea. Evidence for use of psychotropic agents is
      inconclusive; more high-quality trials of longer duration are needed. Evidence
      for the efficacy of 5-HT-receptor antagonists seems favorable, although more
      studies are needed.

PMID- 10896641
TI  - Caring and cost: the challenge for physician advocacy.
AB  - How should physicians respond to the growing tension between care and cost? One
      option is to reinforce the ideal of doing everything to further the best
      interests of the individual patient. Others, however, have argued that because
      health care resources are shared and limited, physicians should consciously
      participate in rationing by saying "no" to patients' requests for some marginally
      beneficial services. But even physicians who endorse the idea of rationing wonder
      whether patient-physician relationships could ever survive a frank admission of
      rationing at the bedside. This article explores the idea that caring about costs
      can be brought to the bedside in a way that will sustain trust among patients and
      the public. By illustrating a hypothetical case and the ensuing conversation
      between a physician and her patient, a mode of "proportional" patient advocacy is
      presented in which physicians can remain forceful agents for patient good while
      acting within a framework that admits to the boundaries of responsible budgets
      for health care needs.

PMID- 10896642
TI  - Risk factors for coronary heart disease in diabetes.

PMID- 10896643
TI  - Epoprostenol for pulmonary hypertension in scleroderma.

PMID- 10896644
TI  - Tatoo-related brachial plexopathies with adjacent muscle atrophy.

PMID- 10896645
TI  - Control group selection is an important but neglected issue in studies of
      antibiotic resistance.

PMID- 10896646
TI  - Mapping it out: using atlases to detect patterns in health care, disease, and
      mortality.

PMID- 10896647
TI  - Nontraditional risk factors for coronary heart disease incidence among persons
      with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study.
AB  - BACKGROUND: Major risk factors explain much of the excess risk for coronary heart
      disease produced by diabetes, but nontraditional factors may also relate to
      incident coronary heart disease. OBJECTIVE: To examine the association of
      traditional and nontraditional risk factors with incidence of coronary heart
      disease in adults with diabetes. DESIGN: Prospective cohort study. SETTING: The
      Atherosclerosis Risk in Communities (ARIC) Study. PARTICIPANTS: 1676 middle-aged
      persons who had diabetes but no history of prevalent coronary heart disease.
      MEASUREMENTS: Multiple risk factors were recorded at baseline. Follow-up was from
      1987 through 1995. RESULTS: 186 participants developed incident coronary heart
      disease events during follow-up. As expected, the incidence of coronary heart
      disease in participants with diabetes was associated positively with traditional
      risk factors (hypertension, smoking, total cholesterol level, and low high
      density lipoprotein [HDL] cholesterol level). After adjustment for sex, age,
      ethnicity, and ARIC field center, incident coronary heart disease was also
      significantly associated with waist-to-hip ratio; levels of HDL3 cholesterol,
      apolipoproteins A-I and B, albumin, fibrinogen, and von Willebrand factor factor
      VIII activity; and leukocyte count. However, after adjustment for traditional
      risk factors for coronary heart disease, only levels of albumin, fibrinogen, and
      von Willebrand factor; factor VIII activity; and leukocyte count remained
      independently associated with coronary heart disease (P < 0.03). The relative
      risks associated with the highest compared with lowest groupings of albumin,
      fibrinogen, factor VIII, and von Willebrand factor values and leukocyte count
      were 0.64 (95% CI, 0.44 to 0.92), 1.75 (CI, 1.12 to 2.73), 1.58 (CI, 1.02 to
      2.42), 1.71 (CI, 1.11 to 2.63), and 1.90 (CI, 1.16 to 3.13), respectively.
      Adjustment for diabetes treatment status attenuated these associations somewhat.
      CONCLUSIONS: Levels of albumin, fibrinogen, and von Willebrand factor; factor
      VIII activity; and leukocyte count were predictors of coronary heart disease
      among persons with diabetes. These associations may reflect 1) the underlying
      inflammatory reaction or microvascular injury related to atherosclerosis and a
      tendency toward thrombosis or 2) common antecedents for both diabetes and
      coronary heart disease.

PMID- 10896649
TI  - Reactive Oxygen Species: From Radiation to Molecular Biology. A festschrift in
      honor of Daniel L. Gilbert. Symposium proceedings. Bethesda, Maryland, USA. July
      2, 1998.

PMID- 10896648
TI  - Reduction in obesity and related comorbid conditions after diet-induced weight
      loss or exercise-induced weight loss in men. A randomized, controlled trial.
AB  - BACKGROUND: The independent effects of diet- or exercise-induced weight loss on
      the reduction of obesity and related comorbid conditions are not known. The
      effects of exercise without weight loss on fat distribution and other risk
      factors are also unclear. OBJECTIVE: To determine the effects of equivalent diet-
      or exercise-induced weight loss and exercise without weight loss on subcutaneous
      fat, visceral fat skeletal muscle mass, and insulin sensitivity in obese men.
      DESIGN: Randomized, controlled trial. SETTING: University research center.
      PARTICIPANTS: 52 obese men (mean body mass index [+/-SD], 31.3 +/- 2.0 kg/m2)
      with a mean waist circumference of 110.1 +/- 5.8 cm. INTERVENTION: Participants
      were randomly assigned to one of four study groups (diet-induced weight loss,
      exercise-induced weight loss, exercise without weight loss, and control) and were
      observed for 3 months. MEASUREMENTS: Change in total, subcutaneous, and visceral
      fat; skeletal muscle mass; cardiovascular fitness; glucose tolerance and insulin
      sensitivity. RESULTS: Body weight decreased by 7.5 kg (8%) in both weight loss
      groups and did not change in the exercise without weight loss and control groups.
      Compared with controls, cardiovascular fitness (peak oxygen uptake) in the
      exercise groups improved by approximately 16% (P < 0.01). Although total fat
      decreased in both weight loss groups (P < 0.001), the average reduction was 1.3
      kg (95% CI, 0.3 to 2.3 kg) greater in the exercise-induced weight loss group than
      in the diet-induced weight loss group (P = 0.03). Similar reductions in abdominal
      subcutaneous, visceral, and visceral fat-to-subcutaneous fat ratios were observed
      in the weight loss groups (P < 0.001). Abdominal and visceral fat also decreased
      in the exercise without weight loss group (P = 0.001). Plasma glucose and insulin
      values (fasting and oral glucose challenge) did not change in the treatment
      groups compared with controls (P = 0.10 for all comparisons). Average improvement
      in glucose disposal was similar in the diet-induced weight loss group (5.6 mg/kg
      skeletal muscle per minute) and in the exercise-induced weight loss group (7.2
      mg/kg skeletal muscle per minute) (P > 0.2). However, these values were
      significantly greater than those in the control and exercise without weight loss
      groups (P < 0.001). CONCLUSIONS: Weight loss induced by increased daily physical
      activity without caloric restriction substantially reduces obesity (particularly
      abdominal obesity) and insulin resistance in men. Exercise without weight loss
      reduces abdominal fat and prevents further weight gain.

PMID- 10896650
TI  - Changes in the antigenicity of a hepatitis B virus mutant stemming from
      lamivudine therapy.

PMID- 10896651
TI  - In vitro development of resistance to ofloxacin and doxycycline in Bacillus
      anthracis Sterne.

PMID- 10896652
TI  - Response to antiretroviral therapy in a patient with an uncommon codon 69
      insertion in the human immunodeficiency virus type 1 reverse transcriptase.

PMID- 10896653
TI  - Diagnostic value of tachypnoea.

PMID- 10896654
TI  - [Compliance in antihypertensive therapy: analyses in scientific articles].
AB  - The aim of this study was to evaluate scientific articles published between 1991
      1995, in order to identify the compliance in antihypertensive therapy, One
      hundred seven scientific articles were evaluated. The results showed that 68%
      were related to patient, 63% to pharmacological treatment, 62% general, 39% non
      pharmacological treatment, 34% organizational factors, and 8% related to disease.
      Compliance with antihypertensive therapy was the major challenge of hypertension
      management and to know how this aspect was focalized in scientific articles
      possible reduce non compliance in hypertension.

PMID- 10896655
TI  - COT kinase proto-oncogene expression in T cells: implication of the JNK/SAPK
      signal transduction pathway in COT promoter activation.
AB  - COT/Tpl-2 proto-oncogene encodes a serine/threonine kinase implicated in cellular
      activation. In this study we have identified the human COT gene promoter region
      and three different human COT transcripts. These transcripts, with the same
      initiation site, display heterogeneity in their 5' untranslated regions and in
      their subcellular localization. Activation of Jurkat T cells with either calcium
      ionophore or alphaCD3 and a phorbol ester increases the levels of the different
      COT transcripts. Analysis of the 5' flanking region of the human COT gene reveals
      a unique transcription initiation site and a TATA element 20 nucleotides
      upstream. Transient expression of COT promoter constructs containing a reporter
      gene indicates that the transcriptional activity of the 5' flanking region of the
      COT gene is regulated by T cell-activating signals. Cotransfection of a dominant
      negative version of SEK-2 abolishes the inducible transcriptional activity of COT
      promoter, indicating that the inducible expression of the COT gene by T cell
      activating signals is mediated by the JNK/SAPK signal transduction pathway. All
      these data indicate stringent regulation of COT kinase proto-oncogene expression.

PMID- 10896656
TI  - Molecular characterization of a first human 3(alpha-->beta)-hydroxysteroid
      epimerase.
AB  - In this report, we describe the isolation and characterization of a cDNA encoding
      an enzyme that exhibits catalytic characteristics of a 3(alpha-->beta)
      hydroxysteroid epimerase (3(alpha-->beta)-HSE). The enzyme overexpressed in human
      293 embryonic kidney cells transforms androsterone into epi-androsterone in two
      steps: the oxidation of androsterone to 5 alpha-androstane-3,17-dione, followed
      by the reduction of the latter to epi-androsterone. The reverse reaction, 3(beta-
      >alpha)-hydroxysteroid epimeration, is approximately 10-fold weaker. These
      results are confirmed by V(max)/K(m) determination, which shows that the enzyme
      catalyzes the oxidation of androsterone to 5 alpha-androstane-3,17-dione and the
      reduction of 5 alpha-androstane-3,17-dione to epi-androsterone more efficiently
      than the reverse reactions. The selective catalysis of the reaction following the
      3(alpha-->beta) direction is also observed in intact transfected cells in
      culture, which better reflect physiological conditions. In vitro assays reveal
      that the recombinant enzyme prefers NAD(+) and NADH as cofactors and could
      recognize both C-19 and C-21 3 alpha-hydroxysteroids as substrates. DNA sequence
      analysis predicts a protein of 317 amino acids. Tissue distribution analysis
      using RT-PCR reveals that the mRNA of the enzyme is expressed in various tissues,
      including liver, brain, prostate, adrenal, and uterus, with the most abundant
      expression in the liver. Because active hydroxysteroids generally exert their
      effect in a stereo-specific manner, 3(alpha-->beta)-HSE could thus potentially
      play an important role in regulating the biological activities of various
      steroids.

PMID- 10896657
TI  - Temperature-dependent arrest of neutrophil apoptosis. Failure of Bax insertion
      into mitochondria at 15 degrees C prevents the release of cytochrome c.
AB  - Apoptosis is essential for the resolution of neutrophilic inflammation. To define
      the mechanisms triggering the execution phase of apoptosis we developed and
      utilized a model in which culture of human neutrophils at 15 degrees C for 20 h
      arrested apoptosis and subsequent warming to 37 degrees C triggered a synchronous
      burst of apoptosis. Treatment of 15 degrees C cultured neutrophils with the pan
      caspase inhibitor zVAD-fmk just before warming to 37 degrees C inhibited the
      morphological changes associated with apoptosis, but did not prevent the
      insertion of the proapoptotic protein Bax into mitochondria nor the inhibition of
      secretion and the externalization of phosphatidylserine, indices of neutrophil
      apoptosis. In both intact neutrophils and a cell-free extract, cytochrome c
      released from mitochondria induced proteolytic cleavage of procaspase-3. At 15
      degrees C the binding of Bax to mitochondria was uncoupled from Bax insertion
      into the mitochondrial membrane required for the release of cytochrome c.
      Apoptosis was also inhibited by low pH during warming to 37 degrees C, suggesting
      that changes to the conformation of Bax, necessary for membrane insertion, were
      being inhibited. Bax insertion was only sensitive to zVAD-fmk when added at the
      start of the 15 degrees C culture period, suggesting that a cytoplasmic substrate
      of the effector caspases may mediate in the mechanism of Bax insertion into
      mitochondria.

PMID- 10896658
TI  - Hepatocyte growth factor-induced differential activation of phospholipase cgamma
      1 and phosphatidylinositol 3-kinase is regulated by tyrosine phosphatase SHP-1 in
      astrocytes.
AB  - Hepatocyte growth factor (HGF) elicits pleiotropic effects on various types of
      cells through the c-Met receptor tyrosine kinase. However, the mechanisms
      underlying the diverse responses of cells remain unknown. We show here that HGF
      promoted chemokinesis of rat primary astrocytes through the activation of
      phosphatidylinositol 3 (PI3)-kinase without any influence on mitogenesis of the
      cells. Under the same condition, phospholipase Cgamma1 (PLCgamma1), which is
      another signal mediator of c-Met, was not tyrosine-phosphorylated during HGF
      stimulation. However, treatment of the cells with orthovanadate, a tyrosine
      phosphatase inhibitor, restored the HGF-induced tyrosine phosphorylation of
      PLCgamma1. A tyrosine phosphatase, SHP-1, was associated with both PI3-kinase and
      PLCgamma1 before HGF stimulation, but it was dissociated only from PI3-kinase
      after the stimulation. Furthermore, transfectants of catalytically inactive
      mutant of SHP-1 showed tyrosine phosphorylation of PLCgamma1 and mitogenic
      responses to HGF, and the mitogenic response was blocked with, an inhibitor of
      phosphatidylinositol-specific PLC, and calphostin C, an inhibitor of protein
      kinase C downstream of the PLCgamma1. These results indicate that PLCgamma1 is
      selectively prevented from being a signal mediator by constitutive association of
      SHP-1, and that this selective inhibition of PLCgamma1 may determine the cellular
      response of astrocytes to HGF.

PMID- 10896659
TI  - The small heat shock protein Hsp22 of Drosophila melanogaster is a mitochondrial
      protein displaying oligomeric organization.
AB  - Drosophila melanogaster has four main small heat shock proteins (Hsps), D.
      melanogaster Hsp22 (DmHsp22), Hsp23 (DmHsp23), Hsp26 (DmHsp26), and Hsp27
      (DmHsp27). These proteins, although they have high sequence homology, show
      distinct developmental expression patterns. The function(s) of each small heat
      shock protein is unknown. DmHsp22 is shown to localize in mitochondria both in D.
      melanogaster S2 cells and after heterologous expression in mammalian cells.
      Fractionation of mitochondria indicates that DmHsp22 resides in the mitochondrial
      matrix, where it is found in oligomeric complexes, as shown by sedimentation and
      gel filtration analysis and by cross-linking experiments. Deletion analysis using
      a DmHsp22-EGFP construct reveals that residues 1-17 and an unknown number of
      residues between 17-28 are necessary for import. Site-directed mutagenesis within
      a putative mitochondrial motif (WRMAEE) at positions 8-13 shows that the first
      four residues are necessary for mitochondrial localization. Immunoprecipitation
      results indicate that there is no interaction between DmHsp22 and the other small
      heat shock proteins. The mitochondrial localization of this small Hsp22 of
      Drosophila and its high level of expression in aging suggests a role for this
      small heat shock protein in protection against oxidative stress.

PMID- 10896660
TI  - Gating of inward rectifier K+ channels by proton-mediated interactions of N- and
      C-terminal domains.
AB  - Ion channels play an important role in cellular functions, and specific cellular
      activity can be produced by gating them. One important gating mechanism is
      produced by intra- or extracellular ligands. Although the ligand-mediated channel
      gating is an important cellular process, the relationship between ligand binding
      and channel gating is not well understood. It is possible that ligands are
      involved in the interactions of different protein domains of the channel leading
      to opening or closing. To test this hypothesis, we studied the gating of Kir2.3
      (HIR) by intracellular protons. Our results showed that hypercapnia or
      intracellular acidification strongly inhibited these channels. This effect relied
      on both the N and C termini. The CO(2)/pH sensitivities were abolished or
      compromised when one of the intracellular termini was replaced. Using purified N-
      and C-terminal peptides, we found that the N and C termini bound to each other in
      vitro. Although their binding was weak at pH 7.4, stronger binding was seen at pH
      6.6. Two short sequences in the N and C termini were found to be critical for the
      N/C-terminal interaction. Interestingly, there was no titratable residue in these
      motifs. To identify the potential protonation sites, we systematically mutated
      most histidine residues in the intracellular N and C termini. We found that
      mutations of several histidine residues in the C but not the N terminus had a
      major effect on channel sensitivities to CO(2) and pH(i). These results suggest
      that at acidic pH, protons appear to interact with the C-terminal histidine
      residues and present the C terminus to the N terminus. Consequentially, these two
      intracellular termini bound to each other through two short motifs and closed the
      channel. Thus, a novel mechanism for K(+) channel gating is demonstrated, which
      involves the N- and C-terminal interaction with protons as the mediator.

PMID- 10896661
TI  - Regulation of brain fatty acid-binding protein expression by differential
      phosphorylation of nuclear factor I in malignant glioma cell lines.
AB  - Brain fatty acid-binding protein (B-FABP) is expressed in the radial glial cells
      of the developing central nervous system as well as in a subset of human
      malignant glioma cell lines. Most of the malignant glioma lines that express B
      FABP also express GFAP, an intermediate filament protein found in mature
      astrocytes. We are studying the regulation of the B-FABP gene to determine the
      basis for its differential expression in malignant glioma lines. By DNase I
      footprinting, we have identified five DNA-binding sites located within 400 base
      pairs (bp) of the B-FABP transcription start site, including two nuclear factor I
      (NFI)-binding sites at -35 to -58 bp (footprint 1, fp1) and -237 to -260 bp
      (fp3), respectively. Competition experiments, supershift experiments with anti
      NFI antibody, and methylation interference experiments all indicate that the
      factor binding to fp1 and fp3 is NFI. By site-directed mutagenesis of both NFI
      binding sites, we show that the most proximal NFI site is essential for B-FABP
      promoter activity in transiently transfected malignant glioma cells. Different
      band shift patterns are observed with nuclear extracts from B-FABP(+) and B-FABP(
      ) malignant glioma lines, with the latter generating complexes that migrate more
      slowly than those obtained with B-FABP(+) extracts. All bands are converted to a
      faster migrating form with potato acid phosphatase treatment, indicating that NFI
      is differentially phosphorylated in B-FABP(+) and B-FABP(-) lines. Our results
      suggest that B-FABP expression in malignant glioma lines is determined by the
      extent of NFI phosphorylation which, in turn, is controlled by a phosphatase
      activity specific to B-FABP(+) lines.

PMID- 10896662
TI  - Intersectin can regulate the Ras/MAP kinase pathway independent of its role in
      endocytosis.
AB  - We previously identified intersectin, a multiple EH and SH3 domain-containing
      protein, as a component of the endocytic machinery. Overexpression of the SH3
      domains of intersectin blocks transferrin receptor endocytosis, possibly by
      disrupting targeting of accessory proteins of clathrin-coated pit formation. More
      recently, we identified mammalian Sos, a guanine-nucleotide exchange factor for
      Ras, as an intersectin SH3 domain-binding partner. We now demonstrate that
      overexpression of intersectin's SH3 domains blocks activation of Ras and MAP
      kinase in various cell lines. Several studies suggest that activation of MAP
      kinase downstream of multiple receptor types is dependent on endocytosis. Thus,
      the dominant-negative effect of the SH3 domains on Ras/MAP kinase activation may
      be indirectly mediated through a block in endocytosis. Consistent with this idea,
      incubating cells at 4 degrees C or with phenylarsine oxide, treatments previously
      established to inhibit EGF receptor endocytosis, blocks EGF-dependent activation
      of MAP kinase. However, under these conditions, Ras activity is unaffected and
      overexpression of the SH3 domains of intersectin is still able to block Ras
      activation. Thus, intersectin SH3 domain overexpression can effect EGF-mediated
      MAP kinase activation directly through a block in Ras, consistent with a
      functional role for intersectin in Ras activation.

PMID- 10896663
TI  - Crystal structure of human squalene synthase. A key enzyme in cholesterol
      biosynthesis.
AB  - Squalene synthase catalyzes the biosynthesis of squalene, a key cholesterol
      precursor, through a reductive dimerization of two farnesyl diphosphate (FPP)
      molecules. The reaction is unique when compared with those of other FPP-utilizing
      enzymes and proceeds in two distinct steps, both of which involve the formation
      of carbocationic reaction intermediates. Because FPP is located at the final
      branch point in the isoprenoid biosynthesis pathway, its conversion to squalene
      through the action of squalene synthase represents the first committed step in
      the formation of cholesterol, making it an attractive target for therapeutic
      intervention. We have determined, for the first time, the crystal structures of
      recombinant human squalene synthase complexed with several different inhibitors.
      The structure shows that SQS is folded as a single domain, with a large channel
      in the middle of one face. The active sites of the two half-reactions catalyzed
      by the enzyme are located in the central channel, which is lined on both sides by
      conserved aspartate and arginine residues, which are known from mutagenesis
      experiments to be involved in FPP binding. One end of this channel is exposed to
      solvent, whereas the other end leads to a completely enclosed pocket surrounded
      by conserved hydrophobic residues. These observations, along with mutagenesis
      data identifying residues that affect substrate binding and activity, suggest
      that two molecules of FPP bind at one end of the channel, where the active center
      of the first half-reaction is located, and then the stable reaction intermediate
      moves into the deep pocket, where it is sequestered from solvent and the second
      half-reaction occurs. Five alpha helices surrounding the active center are
      structurally homologous to the active core in the three other isoprenoid
      biosynthetic enzymes whose crystal structures are known, even though there is no
      detectable sequence homology.

PMID- 10896664
TI  - A vibrational structure of 7,8-dihydrobiopterin bound to dihydroneopterin
      aldolase.
AB  - Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7, 8
      dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin and glycolaldehyde. An
      inhibitor of the enzyme, 7,8-dihydrobiopterin, free in solution and bound in its
      complex with the enzyme has been studied by Raman difference spectroscopy. By
      using isotopically labeled 7,8-dihydrobiopterin and normal mode analyses based on
      ab initio quantum mechanic methods, we have positively identified some of the
      Raman bands in the enzyme-bound inhibitor, particularly the important N5=C6
      stretch mode. The spectrum of the enzyme-bound inhibitor shows that the pK(a) of
      N5 is not significantly increased in the complex. This result suggests that N5 of
      7,8-dihydroneopterin is not protonated before the bond cleavage of 7,8
      dihydroneopterin during the DHNA-catalyzed reaction as has been suggested. Our
      results also show that the N5=C6 stretch mode of 7, 8-dihydrobiopterin shifts 19
      cm(-)(1) upon binding to DHNA. Various possibilities on how the enzyme can bring
      about such large frequency change of the N5=C6 stretch mode are discussed.

PMID- 10896665
TI  - Novel RING finger proteins, Air1p and Air2p, interact with Hmt1p and inhibit the
      arginine methylation of Npl3p.
AB  - Heterogeneous nuclear ribonucleoproteins (hnRNPs) are involved in the mRNA
      processing and export and are post-translationally modified by methylation at
      arginine residues in their arginine-glycine-rich (RGG) domains. We screened the
      factors that can interact with the RGG domain of Npl3p only in the presence of
      Hmt1p with the two-hybrid system in Saccharomyces cerevisiae. An isolated clone,
      YIL079, encodes a novel RING finger protein that was not directly bound to Npl3p
      but associated with the N terminus of Hmt1p. Thus, we designated the gene product
      Air1p (arginine methyltransferase-interacting RING finger protein). Air1p
      inhibited the Hmt1p-mediated methylation of Npl3p in vitro. Overexpression of
      Air1p repressed the Hmt1p-dependent growth of cells. Since homology searches
      indicate that the YDL175 gene product has significant identity (45%) with Air1p,
      we designated the gene AIR2. Air2p also has a RING finger domain and was bound to
      Hmt1p. Although single disruption of either gene gave no effect on the cell
      growth, cells lacking Air1p and Air2p grew at an extremely slow rate with
      accumulated poly(A)(+) RNA in the nucleus. Thus, Air1p and Air2p may affect mRNA
      transport by regulating the arginine methylation state of heterogeneous nuclear
      ribonucleoproteins.

PMID- 10896666
TI  - Multiple histone acetyltransferases are associated with a chicken erythrocyte
      chromatin fraction enriched in active genes.
AB  - We have examined salt-soluble chromatin released by micrococcal nuclease from a
      15-day-old chicken embryo erythrocyte nuclei for histone acetyltransferase (HAT)
      activities. This chromatin is enriched in transcriptionally active sequences from
      within the active beta-globin locus and contains elevated levels of acetylated
      core histones. HAT activities present in this fraction target histones H4, H3,
      and H2A when the chromatin itself is used as the substrate. In gel HAT activity
      assay demonstrates that the salt-soluble chromatin fraction contains four
      acetyltransferase molecules distinguished by their different molecular masses
      (47, 33, 32, and 28 kDa). Further separation of the chromatin by centrifugation
      through sucrose gradients shows that the acetyltransferases segregate into
      chromatin-bound and chromatin-free populations. The 32- and 28-kDa HATs are
      associated with chromatin, whereas the 47- and 33-kDa HAT molecules are not. The
      chromatin-bound HAT activities predominantly target H4 to give the diacetyl and
      triacetyl species; some acetylation of H2A can also be seen. Our results suggest
      that the chromatin-associated acetyltransferases have a role in gene regulation.

PMID- 10896667
TI  - Creating temperature-sensitive winged helix transcription factors. Amino acids
      that stabilize the DNA binding domain of HNF3.
AB  - Winged helix transcription factors contain two polypeptide loops, or "wings,"
      that make minor groove contacts with DNA from either side of a three-helix bundle
      that binds the DNA major groove. While wing 1 is stabilized by a beta-sheet,
      parameters that stabilize wing 2 are unknown. Herein we identify two bulky
      aromatic residues in wing 2 that stabilize the loop structure and, thereby, the
      entire protein's DNA binding and transcriptional stimulatory activity by
      interacting with other residues in the three-helix bundle. Mutations of these
      wing 2 residues create proteins that are temperature-sensitive for
      transcriptional activity. Aromatic and/or hydrophobic residues are highly
      conserved among the 150 known winged helix proteins, suggesting conserved
      function. We suggest that the winged helix structure evolved by the acquisition
      of aromatic and/or hydrophobic residues in distal polypeptide sequences that
      helped stabilize the association of a protein loop (wing 2) with the three-helix
      bundle, thereby enhancing DNA binding.

PMID- 10896668
TI  - Structure of free Thermus flavus 5 S rRNA at 1.3 nm resolution from synchrotron X
      ray solution scattering.
AB  - The shape of free Thermus flavus 5 S rRNA in solution at 1.3 nm resolution is
      restored from synchrotron x-ray scattering data using an ab initio simulated
      annealing algorithm. The free 5 S rRNA is a bent elongated molecule displaying a
      compact central region and two projecting arms, similar to those of the tRNA. The
      atomic models of the 5 S rRNA domains A-D-E and B-C in the form of elongated
      helices can be well accommodated within the shape, yielding a tentative model of
      the structure of the free 5 S rRNA in solution. Its comparison with the recent
      protein-RNA map in the ribosome (Svergun, D. I., and Nierhaus, K. H. (2000) J.
      Biol. Chem. 275, 14432-14439) indicates that the 5 S rRNA becomes essentially
      more compact upon complex formation with specific ribosomal proteins. A
      conceivable conformational change involves rotation of the B-C domain toward the
      A-D-E domain. The model of free 5 S rRNA displays no interactions between domains
      E and C, but such interactions are possible in the bound molecule.

PMID- 10896669
TI  - Subunit composition determines Kv1 potassium channel surface expression.
AB  - Shaker-related or Kv1 voltage-gated K(+) channels play critical roles in
      regulating the excitability of mammalian neurons. Native Kv1 channel complexes
      are octamers of four integral membrane alpha subunits and four cytoplasmic beta
      subunits, such that a tremendous diversity of channel complexes can be assembled
      from the array of alpha and beta subunits expressed in the brain. However,
      biochemical and immunohistochemical studies have demonstrated that only certain
      complexes predominate in the mammalian brain, suggesting that regulatory
      mechanisms exist that ensure plasma membrane targeting of only physiologically
      appropriate channel complexes. Here we show that Kv1 channels assembled as homo-
      or heterotetrameric complexes had distinct surface expression characteristics in
      both transfected mammalian cells and hippocampal neurons. Homotetrameric Kv1.1
      channels were localized to endoplasmic reticulum, Kv1.4 channels to the cell
      surface, and Kv1.2 channels to both endoplasmic reticulum and the cell surface.
      Heteromeric assembly with Kv1.4 resulted in dose-dependent increases in cell
      surface expression of coassembled Kv1.1 and Kv1.2, while coassembly with Kv1.1
      had a dominant-negative effect on Kv1.2 and Kv1.4 surface expression. Coassembly
      with Kv beta subunits promoted cell surface expression of each Kv1 heteromeric
      complex. These data suggest that subunit composition and stoichiometry determine
      surface expression characteristics of Kv1 channels in excitable cells.

PMID- 10896670
TI  - Inhaled anesthetic binding sites in human serum albumin.
AB  - Previous evidence suggests multiple anesthetic binding sites on human serum
      albumin, but to date, we have only identified Trp-214 in an interdomain cleft as
      contributing to a binding site. We used a combination of site-directed
      mutagenesis, photoaffinity labeling, amide hydrogen exchange, and tryptophan
      fluorescence spectroscopy to evaluate the importance to binding of a large domain
      III cavity and compare it to binding character of the 214 interdomain cleft. The
      data show anesthetic binding in this domain III cavity of similar character to
      the interdomain cleft, but selectivity for different classes of anesthetics
      exists. Occupancy of these sites stabilizes the native conformation of human
      serum albumin. The features necessary for binding in the cleft appear to be
      fairly degenerate, but in addition to hydrophobicity, there is evidence for the
      importance of polarity. Finally, myristate isosterically competes with anesthetic
      binding in the domain III cavity and allosterically enhances anesthetic binding
      in the interdomain cleft.

PMID- 10896671
TI  - Nerve growth factor (NGF) loop 4 dimeric mimetics activate ERK and AKT and
      promote NGF-like neurotrophic effects.
AB  - Previous work indicating that nerve growth factor (NGF) protein loops 2 and 4
      interact with TrkA receptors raise the possibility that small molecule mimetics
      corresponding to TrkA-interacting domains that have NGF agonist activity can be
      developed. We applied our previously developed strategy of dimeric
      peptidomimetics to address the hypothesis that loop 4 small molecule dimeric
      mimetics would activate TrkA-related signal transduction and mimic NGF
      neurotrophic effects in a structure-specific manner. A loop 4 cyclized peptide
      dimer demonstrated NGF-like neurotrophic activity, whereas peptides with
      scrambled sequence, added or substituted residues, or cyclized in monomeric form
      were inactive. Activity was blocked by the TrkA inhibitors K252a and AG879 but
      not by NGF p75 receptor blocking antibody. Dimeric, but not monomeric, peptides
      partially blocked NGF activity. This profile was consistent with that of a NGF
      partial agonist. ERK and AKT phosphorylation was stimulated only by biologically
      active peptides and was blocked by K252a. The ERK inhibitor U0126 blocked the
      neurite- but not the survival-promoting activity of both NGF and active peptide.
      These studies support the proof of concept that small molecule NGF loop 4
      mimetics can activate NGF signaling pathways and can mimic death-preventing and
      neurite-promoting effects of NGF. This finding will guide the rational design of
      NGF single-domain mimetics and contribute to elucidating NGF signal transduction
      mechanisms.

PMID- 10896673
TI  - Bcl-2 independence of flavopiridol-induced apoptosis. Mitochondrial
      depolarization in the absence of cytochrome c release.
AB  - The new chemotherapeutic agent, flavopiridol, presently in clinical trials, has
      been extensively studied yet little is known about its mechanism of action. In
      this study we show that the induction of apoptosis by flavopiridol is largely
      independent of Bcl-2. This is indicated by the observation that neither
      overexpression nor the antisense oligonucleotide-mediated down-regulation of Bcl
      2 had any effect on flavopiridol-induced cell killing. Our results suggest that
      flavopiridol can induce apoptosis through different pathways of caspase
      activation with caspase 8 playing a pivotal role. In human lung carcinoma cells,
      which contain high levels of endogenous Bcl-2 and lack procaspase 8, flavopiridol
      treatment leads to mitochondrial depolarization in the absence of cytochrome c
      release, followed by the activation of caspase 3 and cell death. These results
      clearly differ from observations made with other anti-tumor drugs and might
      explain, at least in part, the unusual anti-tumor properties of flavopiridol.

PMID- 10896672
TI  - RhoA prenylation is required for promotion of cell growth and transformation and
      cytoskeleton organization but not for induction of serum response element
      transcription.
AB  - The importance of post-translational geranylgeranylation of the GTPase RhoA for
      its ability to induce cellular proliferation and malignant transformation is not
      well understood. In this manuscript we demonstrate that geranylgeranylation is
      required for the proper cellular localization of V14RhoA and for its ability to
      induce actin stress fiber and focal adhesion formation. Furthermore, V14RhoA
      geranylgeranylation was also required for suppressing p21(WAF) transcription,
      promoting cell cycle progression and cellular proliferation. The ability of
      V14RhoA to induce focus formation and enhance plating efficiency and oncogenic
      Ras anchorage-dependent growth was also dependent on its geranylgeranylation. The
      only biological activity of V14RhoA that was not dependent on its prenylation was
      its ability to induce serum response element transcriptional activity.
      Furthermore, we demonstrate that a farnesylated form of V14RhoA was also able to
      bind RhoGDI-1, was able to induce cytoskeleton organization, proliferation, and
      transformation, and was just as potent as geranylgeranylated V14RhoA at
      suppressing p21(WAF) transcriptional activity. These results demonstrate that
      RhoA geranylgeranylation is required for its biological activity and that the
      nature of the lipid modification is not critical.

PMID- 10896674
TI  - PAPIN. A novel multiple PSD-95/Dlg-A/ZO-1 protein interacting with neural
      plakophilin-related armadillo repeat protein/delta-catenin and p0071.
AB  - A neural plakophilin-related armadillo repeat protein (NPRAP)/delta-catenin
      interacts with one of Alzheimer disease-related gene products, presenilin 1. We
      have previously reported the interaction of NPRAP/delta-catenin with synaptic
      scaffolding molecule, which is involved in the assembly of synaptic components.
      NPRAP/delta-catenin also interacts with E-cadherin and beta-catenin and is
      implicated in the organization of cell-cell junctions. p0071, a ubiquitous
      isoform of NPRAP/delta-catenin, is localized at desmosomes in HeLa and A431 cells
      and at adherens junctions in Madin-Darby bovine kidney cells. We have identified
      here a novel protein interacting with NPRAP/delta-catenin and p0071 and named
      this protein plakophilin-related armadillo repeat protein-interacting PSD-95/Dlg
      A/ZO-1 (PDZ) protein (PAPIN). PAPIN has six PDZ domains and binds to NPRAP/delta
      catenin and p0071 via the second PDZ domain. PAPIN and p0071 are ubiquitously
      expressed in various tissues and are localized at cell-cell junctions in normal
      rat kidney cells and bronchial epithelial cells. PAPIN may be a scaffolding
      protein connecting components of epithelial junctions with p0071.

PMID- 10896675
TI  - Overexpression of membrane domain of SCAP prevents sterols from inhibiting
      SCAP.SREBP exit from endoplasmic reticulum.
AB  - SCAP (SREBP cleavage-activating protein) forms a complex with sterol regulatory
      element-binding proteins (SREBPs) and escorts them from the endoplasmic reticulum
      (ER) to the Golgi complex where proteases release transcriptionally active
      segments of SREBPs, which enter the nucleus to activate lipid synthesis. The
      NH(2)-terminal segment of SCAP contains eight transmembrane helices, five of
      which (TM2-6) comprise the sterol-sensing domain. This domain responds to sterols
      by causing the SCAP.SREBP complex to be retained in the ER, preventing
      proteolytic release and reducing transcription of lipogenic genes. Here, we use
      transfection techniques to overexpress a segment of SCAP containing transmembrane
      helices 1-6 in hamster and human cells. This segment does not interfere with
      SCAP.SREBP movement to the Golgi in the absence of sterols, but it prevents
      sterols from suppressing this movement. This block is abolished when SCAP(TM1-6)
      contains a point mutation (Y298C) that is known to abolish the activity of the
      sterol-sensing domain. We interpret these findings to indicate that sterols cause
      the SCAP.SREBP complex to bind to an ER retention protein through an interaction
      that involves the sterol-sensing domain. The SCAP(TM1-6) segment competes with
      the SCAP.SREBP complex for binding to this putative retention protein, thereby
      liberating the SCAP.SREBP complex so that it can move to the Golgi despite the
      presence of sterols. These studies provide a potential mechanistic explanation
      for the ability of sterols to block SCAP.SREBP movement from the ER and thereby
      to control lipid synthesis in animal cells.

PMID- 10896676
TI  - Translational control of the Xenopus laevis connexin-41 5'-untranslated region by
      three upstream open reading frames.
AB  - The Xenopus laevis Connexin-41 (Cx41) mRNA contains three upstream open reading
      frames (uORFs) in the 5'-untranslated region (UTR). We analyzed the translation
      efficiency of constructs containing the Cx41 5'-UTR linked to the green
      fluorescent protein reporter after injection of transcripts into one-cell stage
      Xenopus embryos. The translational efficiency of the wild-type Cx41 5'-UTR was
      only 2% compared with that of the beta-globin 5'-UTR. Mutation of each of the
      three uAUGs into AAG codons enhanced translation 82-, 9-, and 4-fold compared
      with the wild-type Cx41 5'-UTR. Based on these increased translation
      efficiencies, the percentages of ribosomes that recognized the uAUGs were
      calculated. Only 0.03% of the ribosomes that entered at the cap structure scanned
      the entire 5'-UTR and translated the main ORF. The results indicate that all
      uAUGs are recognized by the majority of the scanning ribosomes and that the three
      uAUGs strongly modulate translation efficiency in Xenopus laevis embryos. Based
      on these data, a model of ribosomal flow along the mRNA is postulated. We
      conclude that the three uORFs may play an important role in the regulation of
      Cx41 expression.

PMID- 10896678
TI  - A heme-binding aspartic proteinase from the eggs of the hard tick Boophilus
      microplus.
AB  - An aspartic proteinase that binds heme with a 1:1 stoichiometry was isolated and
      cloned from the eggs of the cattle tick Boophilus microplus. This proteinase,
      herein named THAP (tick heme-binding aspartic proteinase) showed pepstatin
      sensitive hydrolytic activity against several peptide and protein substrates.
      Although hemoglobin was a good substrate for THAP, low proteolytic activity was
      observed against globin devoid of the heme prosthetic group. Hydrolysis of globin
      by THAP increased as increasing amounts of heme were added to globin, with
      maximum activation at a heme-to-globin 1:1 ratio. Further additions of heme to
      the reaction medium inhibited proteolysis, back to a level similar to that
      observed against globin alone. The addition of heme did not change THAP activity
      toward a synthetic peptide or against ribonuclease, a non-hemeprotein substrate.
      The major storage protein of tick eggs, vitellin (VT), the probable physiological
      substrate of THAP, is a hemeprotein. Hydrolysis of VT by THAP was also inhibited
      by the addition of heme to the incubation media. Taken together, our results
      suggest that THAP uses heme bound to VT as a docking site to increase specificity
      and regulate VT degradation according to heme availability.

PMID- 10896677
TI  - Hepatocyte nuclear factor-3 homologue 1 (HFH-1) represses transcription of smooth
      muscle-specific genes.
AB  - Results show that smooth muscle-specific promoters represent novel downstream
      targets of the winged helix factor hepatocyte nuclear factor-3 homologue 1 (HFH
      1). HFH-1 strongly represses telokin promoter activity when overexpressed in A10
      vascular smooth muscle cells. HFH-1 was also found to repress transcription of
      several other smooth muscle-specific promoters, including the SM22alpha promoter.
      HFH-1 inhibits telokin promoter activity, by binding to a forkhead consensus site
      located within an AT-rich region of the telokin promoter. The DNA-binding domain
      alone was sufficient to mediate inhibition, suggesting that binding of HFH-1
      blocks the binding of other positive-acting factors. HFH-1 does not disrupt serum
      response factor binding to an adjacent CArG box within the telokin promoter,
      implying that HFH-1 must compete with other unidentified trans-activators to
      mediate repression. The localization of HFH-1 mRNA to the epithelial cell layer
      of mouse bladder and stomach implicates HFH-1 in repressing telokin expression in
      epithelial cells. This suggests that cell-specific expression of telokin is
      likely mediated by both positive-acting factors in smooth muscle cells and
      negative-acting factors in nonmuscle cell types. We propose a model in which the
      smooth muscle specificity of the telokin promoter is regulated by interactions
      between positive- and negative-acting members of the hepatocyte nuclear factor
      3/forkhead family of transcription factors.

PMID- 10896679
TI  - Phosphoinositide 3-kinase induces the transcriptional activity of MEF2 proteins
      during muscle differentiation.
AB  - The activity of phosphoinositide 3-kinase (PI3-K) is essential for the
      differentiation of skeletal muscle cells by largely unknown mechanisms. Here we
      show that inhibition of PI3-K activity by the pharmacological agent LY294002
      affects early processes of myoblast differentiation including the transcriptional
      activation of myogenin. Previous studies indicated that transcription of myogenin
      was dependent on MyoD and MEF2 proteins. We find that expression of a dominant
      negative form of PI3-K or growth in the presence of LY294002 inhibits cellular
      activity of MEF2 but not of MyoD. Evidence reveals that whereas MEF2
      transcriptional activity is inhibited, its DNA binding activity remains
      unaffected. Recent studies demonstrated that phosphorylation by p38 mitogen
      activated protein kinase (MAPK) induced transcriptional activity of MEF2
      proteins. We show that the phosphorylation of MEF2 occurring during muscle
      differentiation is prevented if the activity of PI3-K is inhibited. However, our
      results also indicate that p38 MAPK is not affected by PI3-K in muscle cells.
      Nevertheless, p38 MAPK can substitute for PI3-K in the induction of MEF2 and
      muscle transcription. Together, these findings indicate that PI3-K affects
      skeletal muscle differentiation by inducing phosphorylation and transcriptional
      activity of MEF2 proteins in a parallel but distinct route from p38 MAPK.

PMID- 10896680
TI  - Biophysical and structural properties of DNA.diC(14)-amidine complexes. Influence
      of the DNA/lipid ratio.
AB  - Cationic liposomes are used as vectors for gene delivery both in vitro and in
      vivo. Comprehension of both DNA/liposome interactions on a molecular level and a
      description of structural modifications involved, are prerequisites to an
      optimization of the transfection protocol and, thus, successful application in
      therapy. Formation and stability of a DNA/cationic liposome complex were
      investigated here at different DNA:lipid molar ratios (rho). Isothermal titration
      calorimetry (ITC) of cationic liposomes with plasmid DNA was used to characterize
      the DNA-lipid interaction. Two processes were shown to be involved in the complex
      formation. A fast exothermic process was attributed to the electrostatic binding
      of DNA to the liposome surface. A subsequent slower endothermic reaction is
      likely to be caused by the fusion of the two components and their rearrangement
      into a new structure. Fluorescence and differential scanning calorimetry
      confirmed this interpretation. A kinetic model analyzes the ITC profile in terms
      of DNA/cationic liposome interactions.

PMID- 10896681
TI  - Lipoprotein lipase-mediated selective uptake from low density lipoprotein
      requires cell surface proteoglycans and is independent of scavenger receptor
      class B type 1.
AB  - Lipoprotein lipase (LpL) hydrolyzes chylomicron and very low density lipoprotein
      triglycerides to provide fatty acids to tissues. Aside from its lipolytic
      activity, LpL promotes lipoprotein uptake by increasing the association of these
      particles with cell surfaces allowing for the internalization by receptors and
      proteoglycans. Recent studies also indicate that LpL stimulates selective uptake
      of lipids from high density lipoprotein (HDL) and very low density lipoprotein.
      To study whether LpL can mediate selective uptake of lipids from low density
      lipoprotein (LDL), LpL was incubated with LDL receptor negative fibroblasts, and
      the uptake of LDL protein, labeled with (125)I, and cholesteryl esters traced
      with [(3)H]cholesteryl oleoyl ether, was compared. LpL mediated greater uptake of
      [(3)H]cholesteryl oleoyl ether than (125)I-LDL protein, a result that indicated
      selective lipid uptake. Lipid enrichment of cells was confirmed by measuring
      cellular cholesterol mass. LpL-mediated LDL selective uptake was not affected by
      the LpL inhibitor tetrahydrolipstatin but was nearly abolished by heparin,
      monoclonal anti-LpL antibodies, or chlorate treatment of cells and was not found
      using proteoglycan-deficient Chinese hamster ovary cells. Selective uptake from
      HDL, but not LDL, was 2-3-fold greater in scavenger receptor class B type I
      overexpressing cells (SR-BI cells) than compared control cells. LpL, however,
      induced similar increases in selective uptake from LDL and HDL in either control
      or SR-BI cells, indicative of the SR-BI-independent pathway. This was further
      supported by ability of LpL to promote selective uptake from LDL in human
      embryonal kidney 293 cells, cells that do not express SR-BI. In Chinese hamster
      ovary cell lines that overexpress LpL, we also found that selective uptake from
      LDL was induced by both endogenous and exogenous LpL. Transgenic mice that
      overexpress human LpL via a muscle creatine kinase promoter had more LDL
      selective uptake in muscle than did wild type mice. In summary LpL stimulates
      selective uptake of cholesteryl esters from LDL via pathways that are distinct
      from SR-BI. Moreover this process also occurs in vivo in tissues where abundant
      LpL is present.

PMID- 10896682
TI  - Botulinum toxin and spasticity.

PMID- 10896683
TI  - Acoustic neuroma surgery as an interdisciplinary approach.

PMID- 10896684
TI  - Cerebral dysfunction and psychotic symptoms in Alzheimer's disease.

PMID- 10896686
TI  - Acoustic neuroma surgery as an interdisciplinary approach: a neurosurgical series
      of 508 patients.
AB  - OBJECTIVES: To evaluate an interdisciplinary concept (neurosurgery/ear, nose, and
      throat (ENT)) of treating acoustic neuromas with extrameatal extension via the
      retromastoidal approach. To analyse whether monitoring both facial nerve EMG and
      BAEP improved the functional outcome in acoustic neuroma surgery. METHODS: In a
      series of 508 patients consecutively operated on over a period of 7 years,
      functional outcome of the facial nerve was evaluated according to the
      House/Brackmann scale and hearing preservation was classified using the
      Gardner/Robertson system. RESULTS: Facial monitoring (396 of 508 operations) and
      continuous BAEP recording (229 of 399 cases with preserved hearing
      preoperatively) were performed routinely. With intraoperative monitoring, the
      rate of excellent/good facial nerve function (House/Brackmann I-II) was 88.7%.
      Good functional hearing (Gardner/Robertson 1-3) was preserved in 39.8%.
      CONCLUSION: Acoustic neuroma surgery via a retrosigmoidal approach is a safe and
      effective treatment for tumours with extrameatal extension. Functional results
      can be substantially improved by intraoperative monitoring. The interdisciplinary
      concept of surgery performed by ENT and neurosurgeons was particularly convincing
      as each pathoanatomical phase of the operation is performed by a surgeon best
      acquainted with the regional specialties.

PMID- 10896685
TI  - Hereditary spastic paraparesis: a review of new developments.

PMID- 10896688
TI  - Emil theodore kocher (1841-1917)

PMID- 10896687
TI  - Cerebral correlates of psychotic symptoms in Alzheimer's disease.
AB  - BACKGROUND: Psychotic symptoms are produced by distributed neuronal dysfunction.
      Abnormalities of reality testing and false inference implicate frontal lobe
      abnormalities. OBJECTIVES: To identify the functional imaging profile of patients
      with Alzheimer's disease manifesting psychotic symptoms as measured by single
      photon emission computed tomography (SPECT). METHODS: Twenty patients with
      Alzheimer's disease who had SPECT and clinical evaluations were divided into two
      equal groups with similar mini mental status examination (MMSE), age, sex, and
      the range of behaviours documented by the neuropsychiatric inventory (NPI),
      except delusions and hallucinations. SPECT studies, registered to a probabilistic
      anatomical atlas, were normalised across the combined group mean intensity level,
      and subjected to a voxel by voxel subtraction of the non-psychotic minus
      psychotic groups. Subvolume thresholding (SVT) corrected random lobar noise to
      produce a three dimensional functional significance map. RESULTS: The
      significance map showed lower regional perfusion in the right and left
      dorsolateral frontal, left anterior cingulate, and left ventral striatal regions
      along with the left pulvinar and dorsolateral parietal cortex, in the psychotic
      versus non-psychotic group. CONCLUSION: Patients with Alzheimer's disease who
      manifest psychosis may have disproportionate dysfunction of frontal lobes and
      related subcortical and parietal structures.

PMID- 10896689
TI  - Hallucinations, delusions, and cognitive decline in Alzheimer's disease.
AB  - OBJECTIVES: To examine the occurrence of hallucinations and delusions in
      Alzheimer's disease over a 4 year period and their association with rate of
      cognitive decline. METHODS: A cohort of 410 persons with clinically diagnosed
      Alzheimer's disease underwent annual clinical evaluations over a 4 year period.
      Participation in follow up exceeded 90% in survivors. Evaluations included
      structured informant interview, from which the presence or absence of
      hallucinations and delusions was ascertained, and detailed testing of cognitive
      function. The primary cognitive outcome measure was a composite cognitive score
      based on 17 individual performance tests. The mini mental state examination
      (MMSE) and summary measures of memory, visuoconstruction, repetition, and naming
      were used in secondary analyses. RESULTS: At baseline, hallucinations (present in
      41%) and delusions (present in 55%) were common and associated with lower
      cognitive function. In analyses that controlled for baseline level of cognitive
      function, demographic variables, parkinsonism, and use of antipsychotic
      medications, hallucinations, but not delusions, were associated with more rapid
      cognitive decline on each cognitive measure. In the primary model, there was a
      47% increase in the average annual rate of decline on a composite cognitive
      measure in those with baseline hallucinations compared with those without them.
      This effect was mainly due to a subgroup with both auditory and visual
      hallucinations. CONCLUSION: These findings suggest that the presence of
      hallucinations is selectively associated with more rapid cognitive decline in
      Alzheimer's disease.

PMID- 10896690
TI  - Which neuropsychiatric and behavioural features distinguish frontal and temporal
      variants of frontotemporal dementia from Alzheimer's disease?
AB  - OBJECTIVES: To investigate the prevalence of changes in mood, personality, and
      behaviour in frontotemporal dementia (FTD) and Alzheimer's disease (AD) and
      hence, which features reliably distinguish between them. To establish whether the
      frontal and temporal variants of FTD are characterised by different behavioural
      changes. METHODS: A questionnaire was designed to assess a wide range of
      neuropsychiatric changes; it incorporated features reported in previous studies
      of FTD and components of the neuropsychiatric inventory.(1) This was completed by
      37 carers of patients with Alzheimer's disease (AD) and 33 patients with
      frontotemporal dementia (FTD), comprising 20 with temporal variant FTD (tv FTD)
      or semantic dementia and 13 with frontal variant FTD (fv FTD). An exploratory
      principal components factor analysis and discriminant function analysis was
      applied. RESULTS: Factor analysis showed four robust and meaningful symptom
      clusters: factor 1-stereotypic and eating behaviour; factor 2-executive
      dysfunction and self care; factor 3-mood changes; factor 4-loss of social
      awareness. Only stereotypic and altered eating behaviour and loss of social
      awareness reliably differentiated AD from FTD with no effect of disease severity.
      By contrast, executive dysfunction, poor self care, and restlessness showed a
      significant effect of disease severity only, with the more impaired patients
      scoring more highly. Changes in mood were found to be equally prevalent in the
      three patient groups. Analysis of individual symptoms showed increased rates of
      mental rigidity and depression in the patients with semantic dementia compared
      with those with fv FTD. Conversely, the latter group showed greater
      disinhibition. Discriminant function analysis correctly classified 71.4% overall
      and 86.5% of the patients with AD. CONCLUSIONS: This questionnaire disclosed
      striking differences between patients with FTD and AD, but only stereotypic
      behaviour, changes in eating preference, disinhibition, and features of poor
      social awareness reliably separated the groups. The patients with fv FTD and
      semantic dementia were behaviourally very similar, reflecting the involvement of
      a common network, the ventral frontal lobe, temporal pole, and amygdala.
      Dysexecutive symptoms and poor self care were found to be affected by the
      severity of the disease, reflecting perhaps spread to dorsolateral prefrontal
      areas relatively late in the course of both FTD and AD. This questionnaire may be
      of value in the diagnosis and the monitoring of therapies.

PMID- 10896691
TI  - Temporal lobe asymmetry in patients with Alzheimer's disease with delusions.
AB  - OBJECTIVE: To test the hypothesis that delusions are associated with asymmetric
      involvement of the temporal lobe regions in Alzheimer's disease. METHODS:
      Temporal lobe atrophy was assessed with a linear measure of width of the temporal
      horn (WTH) taken from CT films. Temporal asymmetry was computed as the right/left
      (R/L) ratio of the WTH in 22 non-delusional and 19 delusional patients with
      Alzheimer's disease. Delusional patients had paranoid delusions (of theft,
      jealousy, persecution). None of the patients had misidentifications or other
      delusions of non-paranoid content. RESULTS: The R/L ratio indicated symmetric
      temporal horn size in the non-delusional (mean 1. 05 (SD 0.20), and right greater
      than left temporal horn in the delusional patients (mean 1.30, (SD 0.46); t=2.27,
      df=39, p=0.03). When patients were stratified into three groups according to the
      R/L ratio, 47% of the delusional (9/19) and 14% of the non-delusional patients
      (3/21; chi(2)=5.6, df=1, p=0.02) showed right markedly greater than left WTH.
      CONCLUSIONS: Predominantly right involvement of the medial temporal lobe might be
      a determinant of paranoid delusions in the mild stages of Alzheimer's disease.

PMID- 10896692
TI  - Electroencephalographic coherence analysis in multiple sclerosis: correlation
      with clinical, neuropsychological, and MRI findings.
AB  - OBJECTIVE: To explore functional corticocortical connections in multiple
      sclerosis by means of coherence of the EEG, and to evaluate their correlations
      with the degree of cognitive impairment and with brain lesion load assessed by
      MRI. METHODS: EEG coherence was studied from 28 patients with clinically definite
      multiple sclerosis. Ten minutes of resting EEG were recorded with 20 scalp
      electrodes, with binaural reference. FFT power and coherence were calculated in
      artifact free epochs of 1 second and compared with values from 22 control
      subjects of comparable age and sex distribution. Patients also underwent MRI
      (n=27) and neuropsychological examination (n=21). RESULTS: Compared with
      controls, patients with multiple sclerosis showed increased theta power in the
      frontotemporal-central regions (p<0.005). theta Band coherence was decreased
      between homologous areas (p<0.02). alpha Band coherence was decreased both in the
      local and long distance connections (p<0.0005). These findings were most striking
      both in patients with high MRI subcortical lesion load and in patients with
      cognitive involvement. A significant correlation was found between
      interhemispheric theta (p=0.02) and alpha (p=0. 017) and anteroposterior alpha
      (p=0.013) coherence and subcortical MRI lesion load, but not with exclusively
      periventricular lesion load. CONCLUSIONS: These findings support the hypothesis
      that cognitive impairment in multiple sclerosis is mostly dependent on
      involvement of corticocortical connections related to demyelination and/or axonal
      loss within the white matter immediately underlying the cortex.

PMID- 10896693
TI  - Increased expression of insulin-like growth factor I in skin in amyotrophic
      lateral sclerosis.
AB  - OBJECTIVES: Insulin-like growth factor I (IGF-I) has potent effects on motor
      neuron survival and is being studied as a possible therapeutic agent for ALS.
      However, little is known concerning IGF-I in the skin of patients with
      amyotrophic lateral sclerosis (ALS). The aim was to evaluate IGF-I
      immunoreactivity of skin in patients with ALS. METHODS: IGF-I immunoreactivity of
      skin from 18 patients with ALS and 16 controls was examined. RESULTS: IGF-I
      immunoreactivity was markedly positive in the epidermis and dermal blood vessels
      and glands and was moderately positive in the reticular dermis in all patients
      with ALS. On the other hand, the epidermis and dermal blood vessels and glands
      and the reticular dermis showed a weak IGF-I immunoreactivity in controls. The
      optical density for IGF-I immunoreactivity of the epidermis and dermal blood
      vessels and glands, and the reticular dermis in patients with ALS was
      significantly higher than in diseased controls, and was significantly increased
      with duration of illness. CONCLUSIONS: These data suggest that a metabolic
      alteration of IGF-I may take place in the skin of patients with ALS.

PMID- 10896694
TI  - Emotional and cognitive consequences of head injury in relation to the glasgow
      outcome scale.
AB  - OBJECTIVE: There is current debate over the issue of the best way of assessing
      outcome after head injury. One criticism of scales of disability and handicap
      such as the Glasgow outcome scale (GOS) is that they fail to capture the
      subjective perspective of the person with head injury. The aims of the study were
      to investigate aspects of the validity of structured interviews for the GOS, and
      address the issue of the relation between the GOS and subjective reports of
      health outcome. METHODS: A total of 135 patients with head injury were assessed
      using the GOS and an extended GOS (GOSE) and other measures of outcome and
      clinical status at 6 months after injury. RESULTS: There were robust correlations
      between the GOS and measures of initial injury severity (particularly post
      traumatic amnesia) and outcome assessed by disability scales (particularly the
      disbility rating scale (DRS)); however, associations with cognitive tests were
      generally modest. There were also strong correlations with self report measures
      of health outcome: both the GOS and GOSE were related to depression measured by
      the Beck depression inventory, mental wellbeing assessed by the general health
      questionnaire, and to all subscales of the short form-36. The GOS scales were
      also strongly associated with frequency of reported symptoms and problems on the
      neurobehavioural functioning inventory. CONCLUSIONS: The GOS and GOSE show
      consistent relations with other outcome measures including subjective reports of
      health outcome; they thus remain useful overall summary assessments of outcome of
      head injury.

PMID- 10896695
TI  - Volume of focal brain lesions and hippocampal formation in relation to memory
      function after closed head injury in children.
AB  - OBJECTIVES: (1) A study of verbal learning and memory in children who had
      sustained a closed head injury (CHI) at least 3 months earlier. (2) To relate
      memory function to focal brain lesion and hippocampal formation volumes using
      morphometric analysis of MRI. METHODS: A group of 245 children who had been
      admitted to hospital for CHI graded by the Glasgow coma scale (GCS), including
      161 patients with severe and 84 with mild CHI completed the California verbal
      learning test (CVLT) and underwent MRI which was analysed for focal brain lesion
      volume independently of memory test data. Brain MRI with 1.5 mm coronal slices
      obtained in subsets of 25 patients with severe and 25 patients with mild CHI were
      analysed for hippocampal formation volume. Interoperator reliability in
      morphometry was satisfactory. RESULTS: Severity of CHI and age at study
      significantly affected memory performance. Regression analysis showed that
      bifrontal, left frontal, and right frontal lesion volumes incremented prediction
      of various learning and memory indices after entering the GCS score and age into
      the model. Extrafrontal lesion volume did not contribute to predicting memory
      performance. CONCLUSIONS: Prefrontal lesions contribute to residual impairment of
      learning and memory after severe CHI in children. Although effects of CHI on
      hippocampal formation volume might be difficult to demonstrate in non-fatal
      paediatric CHI, further investigation using functional brain imaging could
      potentially demonstrate hippocampal dysfunction.

PMID- 10896696
TI  - Impact of botulinum toxin type A on disability and carer burden due to arm
      spasticity after stroke: a randomised double blind placebo controlled trial.
AB  - OBJECTIVES: After stroke, abnormal arm posture due to spasticity in a
      functionally useless arm may interfere with self care tasks. In these patients
      botulinum toxin treatment presents an opportunity to reduce disability. The
      purpose was to investigate whether reduction in spasticity after botulinum toxin
      treatment translates into reduction in disability and carer burden. METHODS:
      Forty patients with stroke with spasticity in a functionally useless arm (median
      duration 3.1 years) were randomised to receive intramuscular botulinum toxin type
      A (BT-A; Dysport) (n=20) or placebo (n=20) in a total dose of 1000 MU divided
      between elbow, wrist, and finger flexors. Spasticity (using the modified Ashworth
      scale), muscle power, joint movement, and pain were assessed. Disability and
      carer burden were measured using an eight item and a four item scale
      respectively. Two baseline and three post-treatment assessments (weeks 2, 6, and
      12) were made. Concurrent treatments as far as possible remained unchanged and
      not optimised. RESULTS: Disability improved at week 6 with BT-A compared with
      placebo. This effect, present at week 2, wore off by week 12. Reduction in carer
      burden was seen at week 6 with BT-A and continued for at least 12 weeks. Forearm
      flexor spasticity was reduced with BT-A up to 12 weeks after treatment. Although
      significant improvement in elbow flexor spasticity was seen at week 2 with BT-A
      compared with placebo, this effect was not evident at weeks 6 and 12. Arm pain
      was not improved after BT-A. Grip strength was reduced with BT-A. No serious BT-A
      related adverse effects were reported. CONCLUSION: BT-A is useful for treating
      patients with stroke who have self care difficulties due to arm spasticity. The
      decision to treat should also include relief of carer burden. As muscle weakness
      may occur, its potential impact on functional activities must be assessed before
      intervention.

PMID- 10896697
TI  - Neuronal metabolic changes in the cortical region after subcortical infarction: a
      proton MR spectroscopy study.
AB  - OBJECTIVES: To investigate whether proton magnetic resonance spectroscopy ((1)H
      MRS) can detect neuronal metabolic changes in the cortical region in patients
      with cortical dysfunction after subcortical infarction. METHODS: Fifteen patients
      with subcortical large (diameter>/=20 mm) infarcts were studied; nine patients
      with cortical dysfunction (group A), and six without (group B). Seven patients
      with lacunar infarction served as controls. Infarct volume was measured on T2
      weighted images with an image analyser. (1)H MRS data were obtained in three
      regions; high signal intensity area on T2 weighted image, overlying cortex with a
      normal T2 MRI appearance, and contralateral homologous cortical region. RESULTS:
      Infarct volume was not different between groups A and B. N-acetylaspartate
      (NAA)/creatine+phosphocreatine (Cr) ratios in the cortical region overlying
      subcortical infarcts in group A were significantly lower than those in group B
      and the control group (p=0.002). The NAA/Cr ratios in the overlying cortex were
      significantly lower than those in the contralateral normal cortex in group A on
      the initial (p=0. 015) and follow up (p=0.028) (1)H MRS, but these differences
      were not found in group B and the control group. CONCLUSIONS: The results support
      the idea that the cerebral cortex is a responsible location for cortical
      dysfunction after subcortical infarctions. (1)H MRS can be used as a sensitive
      method for the detection of a neuronal metabolic damage, which is not
      demonstrated by conventional MRI.

PMID- 10896699
TI  - Upper limb motor function at 5000 metres: determinants of performance and
      residual sequelae.
AB  - Little is known about the effects of age and symptoms of acute mountain sickness
      and the potential benefit of short term acclimatisation on fine motor performance
      at altitude. There is uncertainty about whether time spent at altitude results in
      permanent neurological sequelae. Nine hole pegboard tests were performed on a
      group of trekkers at sea level (n=61), after ascending to Kanchenjunga base camp
      (5100 m; n=46), and 20 weeks after return to sea level (n=43). Comparison of
      baseline and altitude times showed a mean slowing from 36.2 to 39.0 seconds, a 7.
      8% deterioration in performance (p<0.0001), which was greatest in subjects aged
      50 years or older (5.04 v 1.93 seconds, p=0.017), those tested within 24 hours of
      arrival at 5100 m (4.75 seconds, 13. 3% v 0.48 seconds, 1.3% p<0.001), and
      persons experiencing symptoms of acute mountain sickness (p=0.012), each of which
      were independent determinants of deterioration. Repeat pegboard testing at sea
      level after 20 weeks showed no significant change compared with baseline
      (p=0.68). This confirms the deleterious effects of altitude on fine motor
      function, emphasises the benefit of acclimatisation, and suggests that older
      persons and those with symptoms of acute mountain sickness are particularly
      susceptible. The risk of long term motor dysfunction after exposure to these
      relatively moderate altitudes seems to be small.

PMID- 10896698
TI  - Homocysteine, folate, methylation, and monoamine metabolism in depression.
AB  - OBJECTIVES: Previous studies suggest that folate deficiency may occur in up to
      one third of patients with severe depression, and that treatment with the vitamin
      may enhance recovery of the mental state. There are, however, difficulties in
      interpreting serum and red cell folate assays in some patients, and it has been
      suggested that total plasma homocysteine is a more sensitive measure of
      functional folate (and vitamin B12) deficiency. Other studies suggest a link
      between folate deficiency and impaired metabolism of serotonin, dopamine, and
      noradrenaline (norepinephrine), which have been implicated in mood disorders. A
      study of homocysteine, folate, and monoamine metabolism has, therefore, been
      undertaken in patients with severe depression. METHODS: In 46 inpatients with
      severe DSM III depression, blood counts, serum and red cell folate, serum vitamin
      B12, total plasma homocysteine, and, in 28 patients, CSF folate, S
      adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA,
      and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20
      patients with neurological disorders, the second group undergoing CSF examination
      for diagnostic purposes. RESULTS: Twenty four depressed patients (52%) had raised
      total plasma homocysteine. Depressed patients with raised total plasma
      homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S
      adenosylmethionine and all three CSF monoamine metabolites. Total plasma
      homocysteine was significantly negatively correlated with red cell folate in
      depressed patients, but not controls. CONCLUSIONS: Utilising total plasma
      homocysteine as a sensitive measure of functional folate deficiency, a biological
      subgroup of depression with folate deficiency, impaired methylation, and
      monoamine neurotransmitter metabolism has been identified. Detection of this
      subgroup, which will not be achieved by routine blood counts, is important in
      view of the potential benefit of vitamin replacement.

PMID- 10896700
TI  - Reliance on external cues during serial sequential movement in major depression.
AB  - Maintenance of motor set in patients with unipolar major depression was examined.
      Twelve melancholic and 12 non-melancholic depressed patients and 24 age matched
      controls performed a serial choice reaction time task while external cues aiding
      maintenance of a motor set were systematically removed. Melancholic patients were
      significantly slower than controls with no reduction in external cues and with a
      moderate reduction in external cues. At a high level of reduction in external
      cues, seven of 12 melancholic patients (but only three of 12 non-melancholic
      patients and controls) were unable to complete the task; suggesting a greater
      reliance on external cues, perhaps implicating a failure of motor planning
      ability in melancholic patients. This, in turn, may point to a prefrontal
      (premotor) deficit in melancholic depression, with possible commonalities with
      Parkinson's disease.

PMID- 10896701
TI  - Gut focused behavioural treatment (biofeedback) for constipation and faecal
      incontinence in multiple sclerosis.
AB  - OBJECTIVES: To determine whether gut focused behavioural treatment (biofeedback)
      is a useful therapy in multiple sclerosis patients referred for constipation,
      incontinence, or a combination of these symptoms. Most patients with multiple
      sclerosis complain of constipation, faecal incontinence, or a combination of the
      two. Patients rate these bowel symptoms as having a major impact on their life.
      Until now the management of these problems has been empirical, with a lack of
      evaluated therapeutic regimes. METHODS: Thirteen patients (eight women, median
      age 38 years, median duration of multiple sclerosis 10 years) complaining of
      constipation, with or without faecal incontinence underwent a median of four
      sessions of behavioural treatment. Anorectal physiological tests were performed
      before therapy. Impairment and disability were rated with the Kurtzke score and
      the Cambridge multiple sclerosis basic score (CAMBS). Patients were contacted a
      median of 14 months after completion of treatment. RESULTS: A beneficial effect
      was attributed to biofeedback in five patients. Mild to moderate disability,
      quiescent and non-relapsing disease, and absence of progression of multiple
      sclerosis over the year before biofeedback were predictive of symptom
      improvement. No physiological test predicted the response to therapy. CONCLUSION:
      Biofeedback retraining is an effective treatment in some patients with multiple
      sclerosis complaining of constipation or faecal incontinence. A response is more
      likely in patients with limited disability and a non-progressive disease course.

PMID- 10896702
TI  - Are ictal vocalisations related to the lateralisation of frontal lobe epilepsy?
AB  - The purpose was to analyse whether non-speech vocalisations in seizures
      originating in the frontal lobe do have lateralising value. Patients were
      included who had undergone presurgical evaluation with ictal video-EEG monitoring
      at the Epilepsy Centre, had had resective epilepsy surgery involving the frontal
      lobe, and who had remained seizure free>1 year postoperatively. Twenty seven
      patients aged 1-42 years (mean 18) met the inclusion criteria. Age at epilepsy
      onset ranged from 1 month to 41 years (mean 7.1 years). All selected patients had
      a unilateral MRI detected lesion within the frontal lobe. Fifteen patients had
      right sided, 12 patients had left sided epileptogenic zones. Seizures recorded
      during EEG-video monitoring were re-evaluated to identify the occurrence of ictal
      vocalisations. Pure ictal vocalisations were distinguished from ictal sound
      productions due to motor or vegetative seizure activity (for example, cloni or
      respiratory sounds). Pure ictal vocalisation occurred in 11 patients of whom nine
      had a left frontal epileptogenic zone (p<0.01). It is concluded that ictal
      vocalisation could be an additional lateralising sign in frontal lobe epilepsy.
      The results suggest that not only speech, but vocalisation at a subverbal level
      also shows a left hemispheric dominance in humans.

PMID- 10896703
TI  - Can diffusion weighted magnetic resonance imaging help differentiate stroke from
      stroke-like events in MELAS?
AB  - The precise mechanism of neurological symptoms in patients with mitochondrial
      myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is
      still controversial. The diffusion weighted MR findings at the acute phase of a
      neurological event in MELAS are described and the pathophysiology of stroke-like
      lesion in the light of diffusion changes is discussed. Brain MRI was performed 2
      days after the sudden onset of cortical blindness in a 25 year old patient with
      MELAS. Fluid attenuated inversion recovery (FLAIR) images showed multifocal
      cortical and subcortical hyperintensities located bilaterally in the frontobasal
      and the temporo-occipital lobes. Diffusion weighted images showed normal to
      increased apparent diffusion coefficient values in the acute left
      temporooccipital lesion and increased values in the older stroke-like lesions.
      These diffusion weighted findings support the metabolic rather than the ischaemic
      pathophysiological hypothesis for stroke-like episodes occurring in MELAS. Normal
      or increased apparent diffusion coefficient values within 48 hours of a
      neurological deficit of abrupt onset should raise the possibility of MELAS,
      especially if conventional MR images show infarct-like lesions.

PMID- 10896704
TI  - Phenotypic differences between African and white patients with motor neuron
      disease: a case-control study.
AB  - There is increasing evidence that race may affect the phenotype in some
      neurodegenerative diseases. To investigate this in motor neuron disease a
      retrospective case-control study has been carried out on 15 negroid African and
      45 white patients with the disease seen over 8 years. Each African was compared
      with three age and sex matched white patients with motor neuron disease. There
      were no statistically significant differences in age of onset or the mean
      duration of disease in the two groups. The chance of presenting with the "flail
      arm" variant of motor neuron disease was four times as high in the African group
      than the white group (odds ratio 4.33, p=0. 05, 95% confidence interval 0.99
      18.92). Although no overall differences in survival were seen between the two
      groups, in those with the flail arm variant, four out of the six African patients
      had died whereas all six white arm patients were alive at the censoring date of 1
      January 1999 (median follow up 38.5 months). It is concluded that race may
      influence the phenotype and progression of motor neuron disease.

PMID- 10896705
TI  - Ataxia caused by mutations in the alpha-tocopherol transfer protein gene.
AB  - A 48 year old woman with ataxia with vitamin E deficiency is described. Gene
      analysis identified two point mutations in exon 1 of the alpha-tocopherol
      transfer protein (alpha-TTP) gene, one missense mutation and an upstream
      initiation codon mutation in the 5'-untranslated region (Kozak sequence). The
      latter mutation is the first one identified in the translation regulatory region.
      This mutation decreased the level of alpha-TTP protein expression. The clinical
      features included uncommon urinary disturbance and deafness and relatively rare
      retinitis pigmentosa. Supplementary therapy increased her serum vitamin E
      concentration to the normal range with mild improvement of the deep senses.

PMID- 10896706
TI  - Focal amyotrophy in neurofibromatosis 2.
AB  - Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterised by
      bilateral vestibular schwannomas and other CNS tumours including meningiomas and
      spinal schwannomas. Occasionally, peripheral neuropathy occurs in these patients
      but this is the first report of focal amyotrophy. Clinical, electrophysiological,
      and imaging data from four NF2 patients seen at a specialist neurofibromatosis
      clinic over a 4 year period are described in whom symptomatic focal amyotrophy
      preceded the diagnosis of NF2. Two presented with wasting and weakness of a
      single muscle group, several years before NF2 was diagnosed. In one patient a
      mononeuritis multiplex was the presenting feature of NF2, and in one patient
      focal wasting and weakness developed after the diagnosis of NF2 was made. In none
      of the four cases could a focal peripheral nerve or root neurofibroma be
      identified despite extensive imaging with MRI, and the limitations of
      neuroimaging for identifying a structural cause in patients with NF2 with a focal
      peripheral nerve lesion is discussed. It is likely that NF2 may affect peripheral
      nerve structures in a manner distinct from a compressive schwannoma.

PMID- 10896707
TI  - Course and distribution of facial corticobulbar tract fibres in the lower brain
      stem.
AB  - The course and distribution of the facial corticobulbar tract (CBT) was examined
      by correlating MRI of brain stem lesions with neurological symptoms and signs
      including central (C-FP) or peripheral facial paresis (P-FP) in 70 patients with
      localised infarction of the lower brain stem. C-FP occurred more often in
      patients with lesions of the lower pons or upper medulla of the ventromedial
      brain stem. Some patients with dorsolateral infarcts of the upper medulla to the
      lower pons showed C-FP, mostly on the lesion side. P-FP on the side of the lesion
      was also seen in patients with dorsolateral involvement of the lower pons.
      Patients with ventromedial infarction of the brain stem showed paresis of
      extremities contralateral to the lesion. Specific neurological symptoms and signs
      such as dysphagia, vertigo, nystagmus, Horner's syndrome, ipsilateral cerebellar
      ataxia, and contralateral superficial sensory impairment were seen in patients
      with dorsolateral infarcts of the brain stem. It is hypothesised that the facial
      CBT descends at the ventromedial lower pons, near the corticospinal tract, mainly
      to the level of the upper medulla, where the fibres then decussate and ascend in
      the dorsolateral medulla to synapse in the contralateral facial nucleus.

PMID- 10896708
TI  - Limbic encephalitis and antibodies to Ma2: a paraneoplastic presentation of
      breast cancer.
AB  - A patient with atypical medullary breast cancer is described who presented with
      symptoms of limbic encephalitis. The patient's serum and CSF contained antibodies
      that reacted with the nervous system and the tumour. These antibodies recognised
      Ma2, a neuronal protein related to paraneoplastic limbic and brainstem
      encephalitis in men with testicular tumours. This report highlights the
      importance of testing for paraneoplastic antineuronal antibodies in cases of
      unexplained limbic encephalitis and suggests screening for breast cancer in women
      with antibodies predominantly directed to Ma2.

PMID- 10896709
TI  - Diffusion tensor imaging can detect and quantify corticospinal tract degeneration
      after stroke.
AB  - Diffusion tensor imaging (DTI) fully characterises water molecule mobility in
      vivo, allowing an exploration of fibre tract integrity and orientation in the
      human brain. Using DTI this study demonstrates reduced fibre coherence
      (anisotropy) associated with cerebral infarction and in the corticospinal tract
      remote from the lesion, in five patients 2 to 6 months after ischaemic stroke.
      The study highlights the potential of DTI to detect and monitor the structural
      degeneration of fibre pathways, which may provide a better understanding of the
      pattern of clinical evolution after stroke.

PMID- 10896710
TI  - Multiple lesions originating from the ventricular wall.

PMID- 10896711
TI  - Right ipsilateral hypersensation in a case of anosognosia for hemiplegia and
      personal neglect with the patient's subjective experience.

PMID- 10896712
TI  - The synovial lining: a paradigm for connective tissue research?
AB  - It is to be expected that the extensive researches of Professor Levick and his
      group on the exchange of water and solutes between synovial fluid and the
      microcirculation of the synovial lining will advance understanding of the
      nutrition and lubrication of the synovial joint and of the ways in which
      disturbances in these processes are involved in joint disease. What is less
      expected is the way in which this work has raised, and often definitively
      answered, questions that are pertinent to many other areas of physiology and
      biophysics.

PMID- 10896714
TI  - Residues beyond the selectivity filter of the K+ channel kir2.1 regulate
      permeation and block by external Rb+ and Cs+.
AB  - 1. Kir2.1 channels are blocked by Rb+ and Cs+ in a voltage-dependent manner,
      characteristic of many inward rectifier K+ channels. Mutation of Ser165 in the
      transmembrane domain M2 to Leu (S165L) abolished Rb+ blockage and lowered Cs+
      blocking affinity. At negative voltages Rb+ carried large inward currents. 2. A
      model of the Kir2.1 channel, built by homology with the structure of the
      Streptomyces lividans K+ channel KcsA, suggested the existence of an intersubunit
      hydrogen bond between Ser165 and Thr141 in the channel pore-forming P-region that
      helps stabilise the structure of this region. However, mutations of Thr141 and
      Ser165 did not produce effects consistent with a hydrogen bond between these
      residues being essential for blockage. 3. An alternative alignment between the M2
      regions of Kir2.1 and KcsA suggested that Ser165 is itself a pore-lining residue,
      more directly affecting blockage. We were able to replace Ser165 with a variety
      of polar and non-polar residues, consistent with this residue being pore lining.
      Some of these changes affected channel blockage. 4. We tested the hypothesis that
      Asp172 - a residue implicated in channel gating by polyamines - formed an
      additional selectivity filter by using the triple mutant T141A/S165L/D172N. Large
      Rb+ and Cs+ currents were measured in this mutant. 5. We propose that both Thr141
      and Ser165 are likely to provide binding sites for monovalent blocking cations in
      wild-type channels. These residues lie beyond the carbonyl oxygen tunnel thought
      to form the channel selectivity filter, which the blocking cations must therefore
      traverse.

PMID- 10896713
TI  - The actin cytoskeleton in store-mediated calcium entry.
AB  - Store-mediated Ca2+ entry is the main pathway for Ca2+ influx in platelets and
      many other cells. Several hypotheses have considered both direct and indirect
      coupling mechanisms between the endoplasmic reticulum and the plasma membrane.
      Here we pay particular attention to new insights into the regulation of store
      mediated Ca2+ entry: the role of the cytoskeleton in a secretion-like coupling
      model. In this model, Ca2+ entry may be mediated by a reversible trafficking and
      coupling of the endoplasmic reticulum with the plasma membrane, that shows close
      parallels to the events mediating secretion. As with secretion, the actin
      cytoskeleton plays an inhibitory role in the activation of Ca2+ entry by
      preventing the approach and coupling of the endoplasmic reticulum with the plasma
      membrane, making cytoskeletal remodelling a key event in the activation of Ca2+
      entry. We also review recent advances investigating the regulation of store
      mediated Ca2+ entry by small GTPases and phosphoinositides, which might be
      involved in the store-mediated Ca2+ entry pathway through roles in the
      remodelling of the cytoskeleton.

PMID- 10896715
TI  - Mechanisms for the time-dependent decay of inward currents through cloned Kir2.1
      channels expressed in Xenopus oocytes.
AB  - 1. The decay of inward currents was characterized using the giant patch-clamp
      technique in the cloned inward rectifier K+ channels Kir2.1 expressed in Xenopus
      laevis oocytes. 2. The degree of decay was increased by strong hyperpolarization
      and reduced by increases in external [K+]. This voltage (membrane potential, Vm)-
      and K+-dependent decay is referred to as inactivation. The dissociation constant
      for the protective effects of external K+ ions against inactivation was about 5
      mM and was not Vm dependent. 3. Internal K+ ions also showed mildly protective
      effects against inactivation when external K+ sites were not saturated. Results
      from variations in [K+] suggest that the hyperpolarization-induced inactivation
      of the Kir2.1 channels is not dependent on the driving force for K+ ions. 4. In
      the mutant which demonstrates higher external K+ affinity, the degree of
      inactivation was reduced. These results suggest that binding of K+ ions in the
      external channel pore mouth stabilizes channel opening. 5. Internal Mg2+ and
      polyamines induced time-dependent decay of inward currents in a dose-dependent
      but Vm-independent manner between -150 and -60 mV. The order of potency for Mg2+-
      and polyamine-induced decay was different from that for inward rectification.
      Furthermore, mutations with reduced inward rectification did not show parallel
      reduction of Mg2+- and polyamine-induced decay. These results suggest that the
      effects of internal Mg2+ and polyamines on Kir2.1 channels involve different
      binding sites. 6. This study provides evidence for Vm-dependent processes
      controlling the inactivation of the Kir2.1 channels.

PMID- 10896716
TI  - Inhibition of the K+ channel kv1.4 by acidosis: protonation of an extracellular
      histidine slows the recovery from N-type inactivation.
AB  - 1. Acidosis alters the transient outward current, ito, in the heart. We have
      studied the mechanism underlying the effect of acidosis on one of the K+
      channels, Kv1.4 (heterologously expressed in Xenopus laevis oocytes), known to
      underlie ito. 2. At pH 6.5, wild-type Kv1.4 current was inhibited during
      repetitive pulsing, in part as a result of a slowing of recovery from N-type
      inactivation. 3. Acidosis still caused slowing of recovery after deletion of just
      one (either the first or second) of the N-terminal inactivation ball domains.
      However, deletion of both the N-terminal inactivation ball domains greatly
      reduced the inhibition. 4. As well as the N-terminus, other parts of the channel
      are also required for the effect of acidosis, because, whereas the transfer of
      the N-terminus of Kv1.4 to Kv1.2 conferred N-type inactivation, it did not confer
      acidosis sensitivity. 5. Replacement of an extracellular histidine with a
      glutamine residue (H508Q) abolished the slowing of recovery by acidosis.
      Reduction of C-type inactivation by raising the bathing K+ concentration or by
      the mutation K532Y also abolished the slowing. 6. It is concluded that binding of
      protons to H508 enhances C-type inactivation and this causes a slowing of
      recovery from N-type inactivation and, thus, an inhibition of current during
      repetitive pulsing.

PMID- 10896717
TI  - Superfast contractions without superfast energetics: ATP usage by SR-Ca2+ pumps
      and crossbridges in toadfish swimbladder muscle.
AB  - 1. The rate at which an isometrically contracting muscle uses energy is thought
      to be proportional to its twitch speed. In both slow and fast muscles, however, a
      constant proportion (25-40 %) of the total energy has been found to be used by SR
      Ca2+ pumps and the remainder by crossbridges. We examined whether SR-Ca2+ pumps
      account for a larger proportion of the energy in the fastest vertebrate muscle
      known (the toadfish swimbladder), and whether the swimbladder muscle utilizes
      energy at the superfast rate one would predict from its mechanics. 2. The ATP
      utilization rates of the SR-Ca2+ pumps and crossbridges were measured using a
      coupled assay system on fibres skinned with saponin. Surprisingly, despite its
      superfast twitch speed, the ATP utilization rate of swimbladder was no higher
      than that of much slower fast-twitch amphibian muscles. 3. The swimbladder
      achieves tremendous twitch speeds with a modest steady-state ATP utilization rate
      by employing two mechanisms: having a small number of attached crossbridges and
      probably utilizing intracellular Ca2+ buffers (parvalbumin) to spread out the
      time over which Ca2+ pumping can occur. 4. Finally, although the total ATP
      utilization rate was not as rapid as expected, the relative proportions used by
      SR-Ca2+ pumps and the crossbridges were similar to other muscles.

PMID- 10896718
TI  - P2Y purinoceptor activation mobilizes intracellular Ca2+ and induces a membrane
      current in rat intracardiac neurones.
AB  - 1. The mobilization of Ca2+ by purinoceptor activation and the relative
      contributions of intra- and extracellular sources of Ca2+ were investigated using
      microfluorimetric measurements of fura-2 loaded in cultured neurones from rat
      intracardiac ganglia. 2. Reverse transcriptase-polymerase chain reaction (RT-PCR)
      revealed expression of mRNA for the G protein-coupled P2Y2 and P2Y4 receptors. 3.
      Brief application of either 300 microM ATP or 300 microM UTP caused transient
      increases in [Ca2+]i of 277 +/- 22 nM and 267 +/- 39 nM, respectively. Removal of
      external Ca2+ did not significantly reduce these [Ca2+]i responses. 4. The order
      of purinoceptor agonist potency for [Ca2+]i increases was ATP = UTP > 2-MeSATP >
      ADP >> adenosine, consistent with the profile for P2Y2 purinoceptors. ATP- and
      UTP-induced rises in [Ca2+]i were completely and reversibly blocked by 10 microM
      PPADS (a P2 purinoceptor antagonist) and partially inhibited by 100 microM
      suramin (a relatively non-specific purinoceptor antagonist). 5. In the presence
      of the endoplasmic reticulum Ca2+-ATPase inhibitor cyclopiazonic acid (10 microM)
      in Ca2+-free media, the [Ca2+]i responses evoked by ATP were progressively
      decreased and abolished. 6. ATP- and UTP-induced [Ca2+]i rises were insensitive
      to pertussis toxin, caffeine (5 mM) and ryanodine (10 microM) but were
      significantly reduced by U-73122, a phospholipase C (PLC) inhibitor. 7. In fura-2
      loaded cells, perforated patch whole-cell recordings show that ATP and UTP evoked
      slow outward currents at -60 mV, concomitant with the rise in [Ca2+]i, in
      approximately 30 % of rat intracardiac neurones. 8. In conclusion, these results
      suggest that in r intracardiac neurones, ATP binds to P2Y2 purinoceptors to
      transiently raise [Ca2+]i and activate an outward current. The signalling pathway
      appears to involve a PTX-insensitive G protein coupled to PLC generation of IP3
      which triggers the release of Ca2+ from a ryanodine-insensitive Ca2+ store(s).

PMID- 10896719
TI  - Effects of Mg2+ on Ca2+ release from sarcoplasmic reticulum of skeletal muscle
      fibres from yabby (crustacean) and rat.
AB  - 1. The role of myoplasmic [Mg2+] on Ca2+ release from the sarcoplasmic reticulum
      (SR) was examined in the two major types of crustacean muscle fibres, the tonic,
      long sarcomere fibres and the phasic, short sarcomere fibres of the fresh water
      decapod crustacean Cherax destructor (yabby) and in the fast-twitch rat muscle
      fibres using the mechanically skinned muscle fibre preparation. 2. A robust Ca2+
      induced Ca2+-release (CICR) mechanism was present in both long and short
      sarcomere fibres and 1 mM Mg2+ exerted a strong inhibitory action on the SR Ca2+
      release in both fibre types. 3. The SR displayed different properties with
      respect to Ca2+ loading in the long and the short sarcomere fibres and marked
      functional differences were identified with respect to Mg2+ inhibition between
      the two crustacean fibre types. Thus, in long sarcomere fibres, the submaximally
      loaded SR was able to release Ca2+ when [Mg2+] was lowered from 1 to 0.01 mM in
      the presence of 8 mM ATPtotal and in the virtual absence of Ca2+ (< 5 nM) even
      when the CICR was suppressed. In contrast, negligible Ca2+ was released from the
      submaximally loaded SR of short sarcomere yabby fibres when [Mg2+] was lowered
      from 1 to 0.01 mM under the same conditions as for the long sarcomere fibres.
      Nevertheless, the rate of SR Ca2+ release in short sarcomere fibres increased
      markedly when [Mg2+] was lowered in the presence of [Ca2+] approaching the normal
      resting levels (50-100 nM). 4. Rat fibres were able to release SR Ca2+ at a
      faster rate than the long sarcomere yabby fibres when [Mg2+] was lowered from 1
      to 0. 01 mM in the virtual absence of Ca2+ but, unlike with yabby fibres, the net
      rate of Ca2+ release was actually increased for conditions that were considerably
      less favourable to CICR. 5. In summary, it is concluded that crustacean skeletal
      muscles have more that one functional type of Ca2+-release channels, that these
      channels display properties that are intermediate between those of mammalian
      skeletal and cardiac isoforms, that the inhibition exerted by Mg2+ at rest on the
      crustacean SR Ca2+-release channels must be removed during excitation-contraction
      coupling and that, unlike in crustacean fibres, CICR cannot play the major role
      in the activation of SR Ca2+-release channels in the rat skeletal muscle.

PMID- 10896720
TI  - Adenosine inhibits voltage-dependent Ca2+ currents in rat dissociated supraoptic
      neurones via A1 receptors.
AB  - 1. The modulation of voltage-dependent Ca2+ currents (ICa) by adenosine was
      investigated in magnocellular neurones acutely dissociated from the rat
      hypothalamic supraoptic nucleus (SON) by using the whole-cell patch-clamp
      technique. 2. Adenosine dose dependently and reversibly inhibited ICa elicited by
      depolarizing voltage steps from a holding potential of -80 mV to potentials
      ranging from -30 to +20 mV. The mean (+/- s.e.m.) maximum inhibition rate was
      36.1 +/- 4.1 % (n = 6) at -20 mV and the EC50 was 9.8 x 10-7 M (n = 6). 3. The
      inhibition of ICa by adenosine was completely reversed by the selective A1
      receptor antagonist 8-cyclopentyl theophylline (CPT), and was mimicked by the
      selective A1 receptor agonist N 6-cyclohexyladenosine (CHA). 4. The inhibition by
      CHA was strongly reduced when ICa was inhibited by omega-conotoxin GVIA, a
      blocker of N-type Ca2+ channels. 5. The adenosine-induced inhibition of ICa was
      largely reversed by a depolarizing prepulse to +150 mV for 100 ms, which is known
      to reverse the inhibition of Ca2+ channels mediated by G-protein betagamma
      subunits. 6. The adenosine receptor-mediated inhibition of ICa was not abolished
      by intracellularly applied preactivated pertussis toxin (PTX). 7. Using
      immunohistochemistry, Gzalpha-like immunoreactivity (a PTX-resistant inhibitory G
      protein) was observed throughout the SON. 8. These results suggest that adenosine
      modulates the neuronal activity of SON neurones by inhibiting N-type voltage
      dependent Ca2+ channels via A1 receptors which are coupled to PTX-resistant G
      proteins.

PMID- 10896721
TI  - All classes of calcium channel couple with equal efficiency to exocytosis in rat
      melanotropes, inducing linear stimulus-secretion coupling.
AB  - 1. The contribution of low voltage-activated (LVA) T-type Ca2+ channels and four
      different types of high voltage-activated (HVA) Ca2+ channel to exocytosis, and
      the relationship between calcium influx and exocytosis during action potentials
      (APs) were studied in pituitary melanotropes. 2. Selective HVA Ca2+ channel
      blockers reduced exocytosis, monitored by membrane capacitance measurements,
      proportional to the reduction in Ca2+ influx. The efficacy of Ca2+ in stimulating
      exocytosis did not change in the presence of the Ca2+ channel blockers,
      indicating that all HVA Ca2+ channels act together in stimulating exocytosis. 3.
      The relationship between Ca2+ influx and exocytosis during the AP was examined
      using APs recorded from spontaneously active melanotropes as command templates
      under voltage clamp. Under voltage clamp, multiphasic Ca2+ currents were
      activated over the entire duration of the APs, i.e. during the rising phase as
      well as the plateau phase. The maximum amplitude of the Ca2+ current coincided
      with the peak of the AP. 4. The relationship between Ca2+ entry and exocytosis
      was linear for the different phases of the AP. Also, the influx of Ca2+ through
      LVA T-type channels stimulated exocytosis with the same efficacy as through the
      HVA channels. 5. APs of increasing duration ( approximately 50 to approximately
      300 ms) evoked increasing amounts of exocytosis. The number of entering Ca2+ ions
      and the capacitance change were linearly related to AP duration, resulting in a
      fixed relationship between Ca2+ entry and exocytosis. 6. The results show that
      Ca2+ ions, entering a melanotrope, couple with equal strength to exocytosis
      regardless of the channel type involved. We suggest that the linear relationship
      between Ca2+ entry and secretion observed under physiological conditions (during
      APs), results from the equal strength with which LVA and HVA channels in
      melanotropes couple to exocytosis. This guarantees that secretion takes place
      over the entire duration of the AP.

PMID- 10896722
TI  - A regulator of G protein signalling (RGS) protein confers agonist-dependent
      relaxation gating to a G protein-gated K+ channel.
AB  - 1. The effects of RGS4 on the voltage-dependent relaxation of G protein-gated K+
      (KG) channels were examined by heterologous expression in Xenopus oocytes. 2.
      While the relaxation kinetics was unaffected by the acetylcholine concentration
      ([ACh]) in the absence of RGS4, it became dependent on [ACh] when RGS4 was co
      expressed. 3. Kinetic analyses indicated that RGS4 confers to the KG channel a
      voltage-independent inhibitory gating mechanism, which was attenuated by ACh in a
      concentration-dependent fashion. 4. In vitro biochemical studies showed that RGS4
      could bind to the protein complex containing KG channel subunits. 5. Since the
      native cardiac KG channel exhibited similar agonist-dependent relaxation kinetics
      to that mediated by RGS4, it is suggested that KG channel gating is a novel
      physiological target of RGS protein-mediated regulation.

PMID- 10896723
TI  - Phosphorylation regulates spontaneous and evoked transmitter release at a giant
      terminal in the rat auditory brainstem.
AB  - 1. The role of phosphorylation in synaptic transmission was investigated at a
      large glutamatergic terminal, the endbulb of Held, on bushy cells in the rat
      anteroventral cochlear nucleus (AVCN). 2. Whole-cell recordings of excitatory
      postsynaptic currents (EPSCs) were used to examine the effects of kinase
      inhibitors and activators on low-frequency (baseline) evoked release, spontaneous
      release, paired-pulse facilitation (PPF) or depression (PPD), repetitive stimuli
      and recovery from depression. 3. Application of the kinase inhibitor H7 (100
      microM) reduced low-frequency evoked EPSC amplitude (by 15 %) and simultaneously
      increased PPF (or reduced PPD), with no significant change in other aspects of
      transmission. H7 did not affect the amplitude or frequency of spontaneous
      miniature EPSCs. 4. Phorbol esters increased EPSC amplitude (by 50 %) with a
      concomitant decrease in PPF (or increase in PPD), and reduced the final EPSC
      amplitude during repetitive stimuli. The effect of phorbol esters was due
      exclusively to protein kinase C (PKC) activation, as the specific PKC inhibitor
      bis-indolylmaleimide (Bis) completely blocked the potentiating effect of phorbol
      esters on EPSC amplitude. 5. Significantly, phorbol esters did not increase the
      evoked EPSC amplitude at connections in which release was maximized using high
      extracellular calcium concentrations (4-6 mM). 6. Phorbol esters increased the
      frequency of spontaneous miniature EPSCs in physiological calcium (by 275 %), and
      in high extracellular calcium (by 210 %) when phorbol esters did not increase the
      evoked EPSC amplitude. 7. Our results are most consistent with the actions of H7
      to decrease low-frequency release probability and phorbol esters to increase low
      frequency release probability at the endbulb-bushy cell synaptic connection in
      the AVCN. The effects of H7 and phorbol esters on paired-pulse responses and
      tetanic depression appear to be largely consequential to these changes in low
      frequency release probability.

PMID- 10896724
TI  - Specialised pacemaking cells in the rabbit urethra.
AB  - 1. Collagenase dispersal of strips of rabbit urethra yielded, in addition to
      normal spindle-shaped smooth muscle cells, a small proportion of branched cells
      which resembled the interstitial cells of Cajal dispersed from canine colon.
      These were clearly distinguishable from smooth muscle in their appearance under
      the phase-contrast microscope, their immunohistochemistry and their
      ultrastructure. They had abundant vimentin filaments but no myosin, a
      discontinuous basal lamina, sparse rough endoplasmic reticulum, many mitochondria
      and a well-developed smooth endoplasmic reticulum. 2. Interstitial cells were non
      contractile but exhibited regular spontaneous depolarisations in current clamp.
      These could be increased in frequency by noradrenaline and blocked by perfusion
      with calcium-free solution. In voltage clamp they showed abundant calcium
      activated chloride current and spontaneous transient inward currents which could
      be blocked by chloride channel blockers. 3. The majority of smooth muscle cells
      were vigorously contractile when stimulated but did not show spontaneous
      electrical activity in current clamp. In voltage clamp, smooth muscle cells
      showed very little calcium-activated chloride current. 4. We conclude that there
      are specialised pacemaking cells in the rabbit urethra that may be responsible
      for initiating the slow waves recorded from smooth muscle cells in the intact
      syncitium.

PMID- 10896725
TI  - Ca2+-calmodulin-dependent protein kinase II-dependent activation of contractility
      in ferret aorta.
AB  - 1. The present study was undertaken to determine whether Ca2+-calmodulin
      dependent protein kinase II (CaMKII) participates in the regulation of vascular
      smooth muscle contraction, and if so, to investigate the nature of the downstream
      effectors. 2. The contractility of isolated ferret aorta was measured while
      inhibiting CaMKII either with antisense oligodeoxynucleotides against CaMKII or
      with the CaMKII inhibitor KN93. 3. Treatment with antisense oligodeoxynucleotides
      against CaMKII resulted in, on average, a decrease in protein levels of CaMKII to
      56 % of control levels and significantly decreased the magnitude of the
      contraction in response to 51 mM potassium physiological saline solution (KCl).
      Contraction in response to the phorbol ester DPBA was not significantly affected.
      4. The CaMKII blocker KN93 also resulted in a significant decrease in the force
      induced by 51 mM KCl but caused no significant change in the contraction in
      response to DPBA or the alpha-adrenoceptor agonist phenylephrine. 5. During
      contraction with 51 mM KCl, both CaMKII and mitogen-activated protein kinase
      (MAPK) activity increased, as determined by phospho-specific antibodies. The MAPK
      phosphorylation level was inhibited by KN93, PD098059 (a MAPK kinase (MEK)
      inhibitor) and calcium depletion. 6. Myosin light chain (LC20) phosphorylation
      also increased during contraction with KCl and the increase was significantly
      blocked by PD098059 as well as by both KN93 and antisense oligodeoxynucleotides
      to CaMKII. 7. The data indicate that CaMKII plays a significant role in the
      regulation of smooth muscle contraction and suggest that CaMKII activates a
      pathway by which MAPK activation leads to phosphorylation of LC20 via activation
      of myosin light chain kinase.

PMID- 10896726
TI  - The soma and neurites of primary afferent neurons in the guinea-pig intestine
      respond differentially to deformation.
AB  - 1. Intrinsic primary afferent neurons in the small intestine are exposed to
      distortion of their processes and of their cell bodies. Recordings of
      mechanosensitivity have previously been made from these neurons using
      intracellular microelectrodes, but this form of recording has not permitted
      detection of generator potentials from the processes, or of responses to cell
      body distortion. 2. We have developed a technique to record from enteric neurons
      in situ using patch electrodes. The mechanical stability of the patch recordings
      has allowed recording in cell-attached and whole cell configuration during
      imposed movement of the neurons. 3. Pressing with a fine probe initiated
      generator potentials (14 +/- 9 mV) from circumscribed regions of the neuron
      processes within the same myenteric ganglion, at distances from 100 to 500 microm
      from the cell body that was patched. Generator potentials persisted when synaptic
      transmission was blocked with high Mg2+, low Ca2+ solution. 4. Soma distortion,
      by pressing down with the whole cell recording electrode, inhibited action
      potential firing. Consistent with this, moderate intra-electrode pressure (10
      mbar; 1 kPa) increased the opening probability of large-conductance (BK)
      potassium channels, recorded in cell-attached mode, but suction was not
      effective. In outside-out patches, suction, but not pressure, increased channel
      opening probability. Mechanosensitive BK channels have not been identified on
      other neurons. 5. The BK channels had conductances of 195 +/- 25 pS. Open
      probability was increased by depolarization, with a half-maximum activation at a
      patch potential of 20 mV and a slope factor of 10 mV. Channel activity was
      blocked by charybdotoxin (20 nM). 6. Stretch that increased membrane area under
      the electrode by 15 % was sufficient to double open probability. Similar changes
      in membrane area occur when the intestine changes diameter and wall tension under
      physiological conditions. Thus, the intestinal intrinsic primary afferent neurons
      are detectors of neurite distortion and of compression of the soma, these stimuli
      having opposite effects on neuron excitability.

PMID- 10896727
TI  - Heart rate variability is encoded in the spontaneous discharge of thalamic
      somatosensory neurones in cat.
AB  - 1. We studied the spontaneous discharge variability of thalamocortical
      somatosensory neurones in the awake cat in order to disclose its possible
      information content. The presence of slow (0.09-1.39 Hz) regular fluctuations in
      the discharge rate of these cells during the waking state has been previously
      reported. Oscillations in a similar frequency range are known to characterize the
      activity of central and peripheral neurones pertaining to the autonomic nervous
      system and the variability of heart period (RR interval variability). 2. A
      surrogate data test, performed on our database, confirmed the presence of slow
      (0.05-1 Hz) non-random fluctuations in firing rate. 3. Linear regression detected
      the presence of an inverse relationship between the values of RR interval and the
      concurrent levels of neural discharge. 4. Frequency domain analysis indicated
      that a significant coupling between the two variability signals preferentially
      occurred in two frequency bands: in the frequency of the respiratory sinus
      arrhythmia and in correspondence with a slower rhythm (0.07-0.3 Hz), the two
      signals being in phase opposition in most of the cases. 5. Coherent fluctuations
      could also be observed when epochs of evoked activity were analysed, while
      coupling between the two variability signals appeared to be disrupted after sleep
      onset. 6. We conclude that RR interval variability, an internally generated
      dynamic related to basic visceral regulation, is encoded in the discharge of
      single somatosensory thalamocortical neurones during wakefulness. A possible
      interaction with the transmission of somatosensory information has to be
      evaluated.

PMID- 10896728
TI  - Reduction in renal haemodynamics by exaggerated vesicovascular reflex in rats
      with acute urinary retention.
AB  - 1. We examined the possibility that a vesicovascular reflex is exaggerated by
      acute urinary retention, and that the increase in renal vascular resistance
      caused by this reflex may lead to renal dysfunction. We evaluated the
      vesicovascular responses to normal micturition (NM, transcystometric condition)
      and acute urinary retention (isovolumetric condition mimicking complete bladder
      outlet obstruction (CBOO) and partial urethral ligation mimicking partial bladder
      outlet obstruction (PBOO)) in anaesthetized female Wistar rats. 2. Acute urinary
      retention due to CBOO or PBOO provoked a prolonged or increased intravesical
      pressure, an enhancement in both bladder pelvic afferent and bladder pelvic
      efferent nervous activity, and an elevation in mean arterial blood pressure. 3.
      Single-unit analysis showed that these vesicovascular reflexes were triggered by
      activation of low-threshold and high-threshold bladder mechanoreceptors, but not
      by renal uretropelvic mechanoreceptors. 4. Bladder contraction in CBOO and PBOO
      conditions and graded increases in bladder volume significantly reduced renal
      blood flow and cortical microvascular blood flow. The acute urinary retention
      induced renal vasoconstriction was mediated by the renal nerve. Renal
      denervation, but not bilateral ureteral resection, abolished the renal
      vasoconstriction associated with the vesicovascular reflexes. 5. These findings
      indicate that exaggerated activation of bladder afferents exerts a positive
      feedback effect to increase sympathetic outflow to the kidney further, thereby
      contributing to significant renal vasoconstriction via a renal nerve-dependent
      mechanism.

PMID- 10896729
TI  - Role of cortisol in the ontogenic control of pulmonary and renal angiotensin
      converting enzyme in fetal sheep near term.
AB  - 1. This study examined the ontogeny of angiotensin-converting enzyme (ACE)
      concentration in the lungs and kidneys of fetal, newborn and adult sheep, and
      investigated the effects of cortisol infusion on tissue and plasma ACE in the
      chronically catheterised ovine fetus. 2. Pulmonary and renal ACE in utero
      increased from 113 days of gestation towards term; peak tissue ACE concentrations
      were observed in fetuses studied at 143 days (term, 145 +/- 2 days). The high
      level of ACE seen in the fetal lungs close to term was maintained in the lambs
      and adult ewes whereas renal ACE decreased immediately after birth and rose to a
      maximal value in the adult ewes. In all groups of animals studied, higher mean
      concentrations of ACE were observed in the kidneys than in the lungs. Ontogenic
      increments in pulmonary and renal ACE in utero were coincident with the prepartum
      cortisol surge. In untreated and saline-infused fetuses, plasma cortisol
      correlated with both pulmonary (r = 0.83, P < 0.0001) and renal (r = 0.53, P <
      0.01) ACE concentrations, irrespective of gestational age. 3. An intravenous
      infusion of cortisol (2-3 mg kg-1 day-1) at either 113 or 129 days raised plasma
      cortisol to the level seen near term and caused an increase in pulmonary ACE at
      both gestational ages. Pulmonary ACE concentration in the cortisol-infused
      fetuses at 129 days, but not at 113 days, was similar to that observed in the
      fetuses near term. In contrast, cortisol infusion had no effect on renal ACE
      concentration at either 113 or 129 days of gestation. Plasma ACE concentration
      was also increased by exogenous cortisol at 129 days. 4. Therefore, these
      findings suggest that the ontogenic rise in ACE concentration observed in the
      lungs of the sheep fetus near term is induced, at least in part, by the prepartum
      cortisol surge.

PMID- 10896730
TI  - Autonomic and behavioural thermoregulation in starved rats.
AB  - 1. We investigated the mechanism of starvation-induced hypothermia in rats. 2.
      Threshold core temperatures (Tcor) for tail skin vasodilatation and cold-induced
      thermogenesis were determined after a 3 day starvation using a chronically
      implanted intravenous thermode. Food deprivation significantly lowered the
      threshold Tcor for heat production, but did not affect the heat loss threshold.
      3. Thermogenic response to a fall in Tcor below its threshold was enhanced by
      starvation. 4. Preferred ambient temperatures (Tpref) and Tcor were measured
      before and during a 3 day starvation in a thermal gradient. The 3 day starvation
      significantly lowered Tcor only in the light phase of the day. The level of
      hypothermia was the same throughout the fasting period, while Tpref gradually
      increased during the 3 days of starvation. 5. When rats were starved at a
      constant ambient temperature of 25 C (no thermal gradient), their Tcor levels
      were comparable with those of the rats kept in the thermal gradient. 6. The
      results suggest that, in rats, hypothermia caused by starvation was not due to a
      decrement in thermogenic capability, but was due to a decrease in the threshold
      for the activation of thermogenesis.

PMID- 10896731
TI  - Role of hyaluronan chain length in buffering interstitial flow across synovium in
      rabbits.
AB  - 1. Synovial fluid drains out of joints through an interstitial pathway.
      Hyaluronan, the major polysaccharide of synovial fluid, attenuates this fluid
      drainage; it creates a graded opposition to outflow that increases with pressure
      (outflow 'buffering'). This has been attributed to size-related molecular
      reflection at the interstitium-fluid interface. Chain length is reduced in
      inflammatory arthritis. We therefore investigated the dependence of outflow
      buffering on hyaluronan chain length. 2. Hyaluronan molecules of mean molecular
      mass approximately 2200, 530, 300 and 90 kDa and concentration 3.6 mg ml-1 were
      infused into the knees of anaesthetized rabbits, with Ringer solution as control
      in the contralateral joint. Trans-synovial drainage rate was recorded at known
      joint pressures. Pressure was raised in steps every 30-60 min (range 2-24 cmH2O).
      3. With hyaluronan-90 and hyaluronan-300 the fluid drainage rate was reduced
      relative to Ringer solution (P < 0.001, ANOVA) but increased steeply with
      pressure. The opposition to outflow, defined as the pressure required to drive
      unit outflow, did not increase with pressure, i.e. there was no outflow
      buffering. 4. With hyaluronan-530 and hyaluronan-2000 the fluid drainage rate
      became relatively insensitive to pressure, causing a near plateau of flow.
      Opposition to outflow increased markedly with pressure, by up to 3.3 times over
      the explored pressures. 5. Hyaluronan concentration in the joint cavity increased
      over the drainage period, indicating partial reflection of hyaluronan by synovial
      interstitium. Reflected fractions were 0.12, 0.33, 0.25 and 0.79 for hyaluronan
      90, -300, -530 and -2200, respectively. 6. Thus the flow-buffering effect of
      hyaluronan depended on chain length, and shortening the chains reduced the degree
      of molecular reflection. The latter should reduce the concentration polarization
      at the tissue interface, and hence the local osmotic pressure opposing fluid
      drainage. In rheumatoid arthritis the reduced chain length will facilitate the
      escape of hyaluronan and fluid.

PMID- 10896732
TI  - Effect of indomethacin on capillary growth and microvasculature in chronically
      stimulated rat skeletal muscles.
AB  - 1. Capillary proliferation and microvessel diameters were studied in rat ankle
      flexors subjected to chronic electrical stimulation by implanted electrodes (10
      Hz, 0.3 ms pulse width, up to 6 V, 8 h day-1) for 2 or 7 days with or without
      concurrent indomethacin treatment ( approximately 2 mg day-1 in drinking water)
      to study the role of prostaglandins in the microcirculation in relation to
      capillary growth. 2. Diameters of terminal arterioles, capillaries and confluent
      venules were measured in epi-illuminated muscles, together with capillary red
      cell velocity, to evaluate whether changes in capillary pressure and/or shear
      stress participate in capillary growth via release of prostaglandins. 3. Cell
      proliferation was detected following bromodeoxyuridine (BrdU) incorporation and
      immuno-staining of frozen sections. Labelling was assessed as the percentage of
      all interstitial nuclei (Haematoxylin-stained) that were BrdU positive. By
      comparison with serial sections stained for alkaline phosphatase, from which the
      capillary-to-fibre ratio (C:F) was obtained, labelling was derived for nuclei
      colocalised either to capillaries or to other non-capillary interstitial cells.
      4. C:F increased to 1.89 +/- 0.06 from 1.47 +/- 0.04 in controls only after 7
      days stimulation; indomethacin reduced this to 1.55 +/- 0.07. Capillary labelling
      increased from 2.9 +/- 0.5 % in controls to 11.3 +/- 2.2 % after 2 days
      stimulation and 10.6 +/- 0.8 % after 7 days. The increase was attenuated by
      indomethacin at both time points (to 5.8 +/- 1.6 % and 4.2 +/- 0.5 %,
      respectively). 5. Non-capillary interstitial labelling (2.0 +/- 0.4 % in
      controls) increased to 9.5 +/- 2.7 % after 2 days stimulation and was back to
      normal after 7 days (3.2 +/- 0.7 %). Indomethacin depressed the increase at 2
      days to 4.0 +/- 1.3 % and had no effect at 7 days (2.9 +/- 0.13 %). Labelling in
      sham-operated rats with or without indomethacin or in vehicle-treated animals was
      no different from controls. 6. Arteriolar and venular diameters were increased by
      2 days of stimulation but unchanged after 7 days. Indomethacin increased
      diameters of arterioles after 2 days and venules after 7 days in sham-operated
      animals, but had no effect on diameters of either vessel type in stimulated
      muscles. 7. Capillary diameters did not change during acute muscle contractions
      whereas red cell velocity did. Calculated shear stress in capillaries was thereby
      increased by 75 %. 8. Thus during chronic electrical stimulation both capillary
      growth and the cell proliferation that precedes it were attenuated by
      indomethacin. Transient stimulation-induced increases in arteriolar and venular
      diameters, which were unaffected by indomethacin, do not implicate increased
      capillary pressure as a factor in prostaglandin release and capillary growth.
      Estimations of increases in capillary shear stress during muscle contractions and
      of a 45 % higher value even at rest after chronic stimulation for 7 days suggest
      that shear stress is a more likely stimulus for prostaglandin release in
      chronically stimulated muscles.

PMID- 10896733
TI  - Comparison of contractile properties of single motor units in human intrinsic and
      extrinsic finger muscles.
AB  - 1. The purpose of the present study was to compare the contractile properties of
      single motor units in the intrinsic (short) and extrinsic (long) finger muscles
      in awake human subjects using intraneural motor axon stimulation. 2. Twitch
      properties were measured for 17 intrinsic and 11 extrinsic motor units by
      selective stimulation of a single motor axon in the ulnar or the median nerve.
      Force was measured from the appropriate digit, just distal to the muscle's point
      of insertion and single unit EMG was recorded with surface electrodes. Force
      frequency relationships (2-100 Hz) were established for 16 of these units (7
      intrinsic, 9 extrinsic). Across the 16 motor units for which force-frequency data
      were obtained, twitch contraction time (63.7 +/- 6.0 ms, mean +/- s.e.m.) was
      inversely correlated with the frequency required to generate half-maximum tetanic
      force (12.0 +/- 1.1 Hz). 3. We found no systematic differences between the
      contractile properties of intrinsic and extrinsic motor units. There was no
      evidence of a bimodal distribution into large/small or fast/slow units based on
      maximum force or contraction times, although both fast and slow motor units were
      encountered. 4. The peak slope of the sigmoidal force-frequency relationship for
      intrinsic motor units (9.1 and 4.4-12.9 mN Hz-1, median and interquartile range)
      was significantly higher than that for extrinsic motor units (2.9 and 2.3-3.1 mN
      Hz-1; P = 0.028), i.e. greater force steps were produced by the intrinsic motor
      units for a given change in stimulation frequency. This difference suggests that
      motor units in the intrinsic muscles of the hand are more sensitive to modulating
      force output by changes in motoneurone firing rates than are those in the
      extrinsic muscles. This reflects the important role of the intrinsic hand muscles
      in the fine manipulation of objects.

PMID- 10896734
TI  - Stretch reflex distinguished from pre-programmed muscle activations following
      landing impacts in man.
AB  - 1. Electromyographic activity and joint rotation were measured whilst human
      subjects jumped down to land on a solid surface 0.45 m below them and then to a
      false collapsible surface at the same level. The collapsible surface did not
      produce ankle joint rotation. Objective evidence from post-take-off EMG onset
      latencies showed that the subjects were surprised by the false surface. 2.
      Following landing on the solid surface, the gastrocnemius and soleus muscles
      showed peak responses at latencies of 53 and 56 ms, respectively, and the
      antagonist m. tibialis anterior showed an early peak response with a latency of
      26 ms. These responses occurred following landing on the solid surface but not
      following passage through the false surface. 3. The rectus femoris and biceps
      femoris muscles showed no clear reflex activity with this fall distance but pre
      programmed activity was clearly present following impact. 4. It is concluded that
      the post-landing activity in m. soleus and m. gastrocnemius is a short-latency
      spinal reflex triggered by ankle joint rotation.

PMID- 10896735
TI  - Adverse outcomes in group psychotherapy: risk factors, prevention, and research
      directions.
AB  - Group forms of therapy have been growing at a rapid rate, in part because of
      their documented effectiveness and economic considerations such as managed care.
      It is therefore becoming increasingly important to assess the psychological risks
      of these interventions. The author provides an overview of the published
      literature and conference presentations on negative effects in adult outpatient
      groups. Although much of the literature on adverse outcomes in group therapy
      focuses on single risk factors (e.g., negative leader, group process, or patient
      characteristics), the author argues that an interactional model should be
      encouraged. Means of reducing casualties are also discussed, as well as
      methodological issues and research directions.

PMID- 10896736
TI  - The role of therapist characteristics in training effects in cognitive,
      supportive-expressive, and drug counseling therapies for cocaine dependence.
AB  - The role of therapist characteristics in therapy training was examined for 62
      therapists in a multisite psychotherapy outcome study that included cognitive
      therapy (CT), supportive-expressive (SE) psychodynamic therapy, and individual
      drug counseling (IDC) for cocaine-dependent patients. Demographic variables and
      experience and competence ratings prior to training were correlated with measures
      of change in competence during the training phase. Higher competence ratings
      before training were associated with greater change in competence for SE and
      higher average competence for IDC. More years of experience were associated with
      greater change in competence for CT therapists, but more hours of pre-training
      supervision in the CT treatment modality were associated with less change.

PMID- 10896737
TI  - Rater agreement on interpersonal psychotherapy problem areas.
AB  - There has been much outcome research on interpersonal psychotherapy (IPT) but
      little investigation of its components. This study assessed interrater
      reliability of IPT therapists in identifying interpersonal problem areas and
      treatment foci from audiotapes of initial treatment sessions. Three IPT research
      psychotherapists assessed up to 18 audiotapes of dysthymic patients, using the
      Interpersonal Problem Area Rating Scale. Cohen's kappa was used to examine
      concordance between raters. Kappas for presence or absence of each of the four
      IPT problem areas were 0.87 (grief), 0.58 (role dispute), 1.0 (role transition),
      and 0.48 (interpersonal deficits). Kappa for agreement on a clinical focus was
      0.82. IPT therapists agreed closely in rating problem areas and potential
      treatment foci, providing empirical support for potential therapist consistency
      in this treatment approach.

PMID- 10896738
TI  - Under attack: devaluation and the challenge of tolerating the transference.
AB  - Devaluation presents one of the therapist's most difficult challenges: conducting
      therapy and managing resistance with patients who force the therapist into very
      aggressive and uncomfortable experiences. When these situations arise, the
      therapist has a twofold task. He or she must tolerate the transference so as not
      to engage in a countertransferential enactment. Additionally, from this
      vulnerable vantage point, he or she must help the patient understand both the
      meaning of and the consequences of devaluations of the therapist. Two cases are
      presented that recognize devaluation as an example of projective identification
      and illustrate the challenge in working with this dynamic.

PMID- 10896739
TI  - Inadequacy and indebtedness: no-fee psychotherapy in county training programs.
AB  - The nature of the fee arrangement has significant influence on the
      psychotherapeutic process even when there is no fee. Given the large number of
      psychiatrists who receive at least some part of their training in the public
      system, understanding the no-fee arrangement is vital to the psychodynamic
      training of future psychiatrists. Following a brief overview of the meaning of
      money and the fee arrangement, various scenarios are considered under the
      headings of "inadequacy" and "indebtedness. "Although similar dynamics may be
      present in other public and private settings, attention is given to the county
      training program, with the intent to assist psychiatry residents and supervisors
      in their awareness and understanding of the psychodynamics of psychotherapy
      without fee.

PMID- 10896740
TI  - Development of an integrated cognitive-behavioral and social skills training
      intervention for older patients with schizophrenia.
AB  - There is considerable evidence that psychosocial treatments benefit younger
      adults with schizophrenia. However, no studies have been undertaken of such
      interventions for older patients with schizophrenia. This report describes the
      development of a novel integrated treatment combining cognitive-behavioral
      therapy (CBT) and social skills training (SST). This intervention is designed to
      address the needs of older patients with schizophrenia by challenging beliefs
      common in this population that interfere with treatment and by providing
      repetitive practice of behaviors to improve retention and skill development. The
      authors provide two case reports and pilot data suggesting benefits of this
      approach.

PMID- 10896741
TI  - "Moving along" in psychotherapy with schizophrenia patients.
AB  - Current treatment of the schizophrenic patient relies primarily on
      psychopharmacological management, psychoeducation, and family work. If individual
      psychotherapy is an adjunct, it is generally supportive. Recent focus on
      determinants of change in classical psychoanalysis suggests that noninterpretive
      mechanisms may have an impact at least equivalent to that of the well-timed
      transference interpretation. The author argues that the same noninterpretive
      mechanisms may be even more important for change in patients in a supportive
      process. A case study is used to illustrate that such an application of
      psychoanalytic principles and developmental research can be used to help even the
      most disturbed patients.

PMID- 10896742
TI  - Reimbursement options for WOC(ET) nurses in the long-term care setting.

PMID- 10896743
TI  - Show me the data.

PMID- 10896744
TI  - The voice of experience.

PMID- 10896745
TI  - Quasiexperimental designs.

PMID- 10896746
TI  - A national study of pressure ulcer prevalence and incidence in acute care
      hospitals.
AB  - OBJECTIVE: This study sought to establish national benchmarks for pressure ulcer
      prevalence and incidence among acute care health organizations served by Novation
      LLC. SETTING AND SUBJECTS: One hundred sixteen acute care facilities from 34
      states participated; the sample consisted of 17,560 patients in hospital-based
      medical-surgical or intensive care units. INSTRUMENTS: Standardized education
      kits were provided to each participating site. The kits included an educational
      video about pressure ulcer staging, a post-test and answer key, and assessment
      form for patient data collection. METHODS: Pressure ulcer prevalence was measured
      during a predetermined 24-hour period at each facility. Incidence was measured
      over the average length of stay determined for each participating facility.
      Subjects were assessed by teams consisting of a registered nurse and one other
      health care professional (e.g. licensed practical nurse, physical therapist).
      Demographic, wound, and other data were collected for these patients. Data
      collection forms were audited and submitted to a central site for database entry,
      analysis, and generation of reports. RESULTS: The average length of stay for the
      participating facilities was 5 days. Pressure ulcers developed in 7% of the
      subjects (n = 383); 90% were stage I or II pressure ulcers, and 73% occurred in
      patients older than 65 years. The most sites based on both prevalence and
      incidence measurements were the sacrum and coccyx at 26% and 31%, respectively.
      CONCLUSIONS: Prevalence and incidence studies must be routinely conducted to
      clearly identify the extent of the pressure ulcer problem to provide guidance for
      efficient and effective corrective action.

PMID- 10896747
TI  - Patients with existing pressure ulcers admitted to acute care.
AB  - PURPOSE: This study describes the characteristics of patients with pressure
      ulcers present on admission to the hospital and predictors of pressure ulcer
      presence and severity. DESIGN: Prospective cohort study. SETTING AND SUBJECTS:
      Adults (n = 267) admitted to a Pacific Basin military hospital who were expected
      to stay more than 24 hours. INSTRUMENTS: Braden scale, portable vital sign
      machine, and pulse oximeter. METHODS: Pressure ulcer risk was evaluated and skin
      inspection was performed. Demographic, physiologic, and laboratory data were
      obtained. Medical history and patient acuity were recorded. RESULTS: Thirty-four
      of 267 subjects (12.8%) had a pressure ulcer. Most were male and white. Their
      mean age was 65.7 years; mean albumin level, 2.9 g/dL: mean hematocrit level,
      31.9 vol%; mean oxygen saturation, 95.3 mm Hg; and mean hemoglobin level, 10.7
      g/dL. The mean Braden scale score for subjects without ulcers on admission was
      19.7, and it was 15.9 for those with ulcers (P < .05). Analysis of variance
      showed that subjects with pressure ulcers had a significantly lower albumin
      level, total lymphocyte count, hematocrit level, and hemoglobin level. These
      subjects were significantly older and had a longer hospital length of stay.
      Regression showed that albumin level, oxygen saturation, and length of stay (P <
      .01) accounted for 11.3% of the variance of pressure ulcer presence and that
      albumin level and length of stay (P < .001) accounted for 11.2% of the variance
      in ulcer severity. CONCLUSIONS: Poorer nutritional status and decreased oxygen
      perfusion were predictors of pressure ulcers on admission. Nutrition and length
      of stay were predictors of ulcer severity. Further research is warranted.

PMID- 10896748
TI  - Psychosocial adjustment, coping, and quality of life in persons with venous
      ulcers and a history of intravenous drug use.
AB  - OBJECTIVE/PURPOSE: Psychosocial adjustment, coping, and quality of life for
      persons with a venous ulcer and a history of intravenous drug use were examined.
      DESIGN: A cross-sectional design was used. SETTING AND SUBJECTS: Data were
      collected in an urban outpatient clinic. All eligible persons were asked to
      participate. Thirty-two patients agreed to participate, providing an 89% response
      rate. The mean age of participants was 44.6 years (SD = 4.3); 91% were African
      American, and 72% were male. INSTRUMENTS: Subjects responded to questions about
      their health and substance abuse history and completed the Quality of Life With a
      Leg Ulcer Questionnaire, Psychosocial Adjustment to Illness Scale (PAIS), Ways of
      Coping Instrument, and Pain Questionnaire. Leg ulcer tracings were measured with
      the SigmaScan computer program. METHODS: Questionnaires were read to
      participants. Leg ulcers were traced at their borders onto plastic. RESULTS:
      Wound area correlated significantly with the domestic environment (r = .43) and
      the psychosocial distress (r = .38) scores of the PAIS. Wound area was negatively
      correlated to Quality of Life With a Leg Ulcer Questionnaire score (r = -.52).
      Pain interference was significantly related to the self-controlling coping score
      (r = .40), domestic environment score of the PAIS (r = .51), and Quality of Life
      With a Leg Ulcer Questionnaire score (r = -.65). Cox and Wermuth's multiple
      regression modeling approach was used to summarize the study's variables.
      CONCLUSIONS: A larger wound area was associated with greater illness-induced
      difficulties in the home environment, greater psychological distress, and poor
      quality of life. Pain Interference was associated with a greater effort to
      regulate one's feelings and actions, difficulties in the home, and poor quality
      of life.

PMID- 10896749
TI  - Notes on methodology. Reliability coefficients.

PMID- 10896750
TI  - A self-directed home biofeedback system for women with symptoms of stress, urge,
      and mixed incontinence.
AB  - PURPOSE: To evaluate a self-directed home biofeedback treatment system in a group
      of community dwelling, otherwise healthy women with symptoms of stress, urge, and
      mixed urinary incontinence (UI). SETTING AND SUBJECTS: Fifty-five women, aged 25
      to 81 years, participated in the study. METHODS: Initial evaluation included a
      self-reported continence assessment, a 24-hour bladder and fluid habits diary,
      severity indices for stress and urge UI, and assessment of pelvic floor strength
      using a pneumatic biofeedback device. Subjects completed a 16-week self-directed
      program. Assessment and severity index data were self-reported using a continence
      assessment form, a 24-hour bladder habit and fluid form, and stress and urge
      incontinence severity indices. Strength level of the trainer, number of digital
      bands lit on the screen during contraction, number of sessions, and program
      (starter, intermediate, advanced, or maintenance) were recorded on data sheets.
      INSTRUMENTS: The treatment system includes an 8-minute educational and
      motivational video; a journal for education, instructions, and daily
      documentation forms; and a home biofeedback trainer with pneumatic vaginal
      sensors that displays the strength of pelvic muscle contraction. RESULTS: Forty
      four women completed the 16-week program. At the end of treatment, 19 (43%) were
      dry and 16 (36%) reported 50% or more improvement in number of leaks per day,
      number of voids per day, or both. Women with stress leakage experienced a
      significant reduction in the number of incontinent episodes per day and the mean
      severity index of incontinence (P < .001). Participants with urge UI experienced
      a significant reduction in the mean number of voids per day and mean severity
      index for UI (P < .001). Younger subjects were more likely to improve when
      compared with older participants, but no significant differences were found when
      comparing women who take estrogen with those who do not take estrogen or when
      comparing those with a history of bladder surgery with those who had no previous
      surgery. CONCLUSIONS: These data suggest that self-selected healthy women with
      symptoms of urge, stress, and mixed incontinence can improve their symptoms and
      lower their severity index with a minimal intervention, comprehensive, self
      directed home biofeedback continence system.

PMID- 10896752
TI  - National association of clinical nurse specialists represents the CNS

PMID- 10896751
TI  - Care of metastatic skin lesions.

PMID- 10896753
TI  - National association of clinical nurse specialists represents the CNS

PMID- 10896754
TI  - Credit for idea to use ziploc storage bag

PMID- 10896755
TI  - State-dependent barium block of wild-type and inactivation-deficient HERG
      channels in Xenopus oocytes.
AB  - The effects of Ba2+ on current resulting from the heterologous expression of the
      human ether-a-go-go related gene (HERG) (IHERG) was studied with two-electrode
      voltage clamp techniques in Xenopus oocytes. Ba2+ produced time- and voltage
      dependent block of IHERG. Significant inhibition was seen at concentrations as
      low as 1 microM. Inhibition was greatest at step potentials between -40 and 0 mV;
      at more positive potentials, inhibition decreased in association with time
      dependent unblocking of channels. An inactivation-attenuated mutant of HERG
      (S631A) was prepared and expressed in Xenopus oocytes. Ba2+ block of S631A
      differed from that of HERG in that extensive unblocking was no longer seen at
      positive potentials and the voltage dependence of step current block was greatly
      attenuated. A mathematical model was applied to analyse quantitatively the
      inhibitory effects of Ba2+ on IHERG. The model suggested similar voltage
      dependent affinity of Ba2+ for the open and closed states, along with absence of
      binding to the inactivated state, and accounted well for Ba2+ effects on both
      wild-type and S631A channels. We conclude that Ba2+ potently inhibits IHERG in a
      characteristic state-dependent fashion, with strong unblocking at positive
      potentials related to the presence of an intact C-type inactivation mechanism.

PMID- 10896757
TI  - Effects of metabolic inhibitors on ingestive behavior and physiology in
      preweanling rat pups.
AB  - We have previously demonstrated that administration of 2-Mercaptoacetate (MA)
      stimulates independent intake after 1 h in 12 and 15-day-old rat pups, but not
      younger pups. MA also produces decreases in beta-HBA levels, consistent with the
      development of a role of altered fatty acid oxidation in modulating independent
      ingestion in rat pups by 12 days of age. The present experiments extended
      investigations of the role of changes in energy utilization in young rats by
      investigating the duration of the effects of altered fatty acid oxidation and the
      effects of combined blockade of fatty acid oxidation and glucose utilization.
      Pups were tested at 9, 12 or 15 days of age 3 or 6 h following administration of
      a dose of 0, 11.4, 22.8, 45.6 or 91.2 mg/kg MA. In pups aged 12 and 15 days,
      moderate doses of MA stimulated intake 3 h, but not 6 h, following
      administration. Administration of the highest dose of MA produced significant
      decreases in beta-HBA levels in pups at all ages when tested after 3 h, but not
      after 6 h. In the second set of experiments, behavioral and physiological
      responses to administration of MA (0, 11.4 or 22.8 mg/kg) combined with 2
      Deoxyglucose (2-DG: 0, 100 or 200 mg/kg) were investigated in pups aged 6, 9, 12
      or 15 days of age. The results demonstrated that while administration of 2-DG
      produced physiological responses, intake was not stimulated at any age by 2-DG
      alone or in combination with MA. In fact, in 12 and 15-day-old pups,
      administration of 2-DG blocked the stimulatory effects of administration of MA.
      Therefore, while altered utilization of glucose does not appear to be an
      effective stimulus for increased independent ingestion in pups at this age,
      altered fatty acid oxidation may be an early metabolic modulator of intake.

PMID- 10896756
TI  - Swimming eliminates the weight gain and abdominal fat associated with ovariectomy
      in the retired breeder rat despite high-fat diet selection.
AB  - The effects of swim-training on choice of dietary fat, carbohydrate or protein,
      weight gain, energy intake, and energy efficiency were examined in ovariectomized
      and sham-operated retired breeder rats. After a 3 week training period of
      increased duration, rats swam for 75 min per session (5 days per week) for 4
      weeks. Ovariectomized rats gained more weight than sham rats, while swimming
      reduced weight gain and abdominal fat. As a percentage of total intake,
      macronutrient choices (weight and energy) were similar for all groups,
      ovariectomized animals consumed more food and more energy, compared with sham
      animals. All rats freely chose the majority of their food (g) as carbohydrate and
      the majority of energy (kJ) as fat. Results indicate that a moderate intensity
      training program of swimming prevented the weight gain following ovariectomy in
      older rats despite their excessive caloric intake of fat.

PMID- 10896758
TI  - Responsivity to food cues in bulimic women and controls.
AB  - The current study investigated responsivity to individualized food cues
      consisting of binge/favourite foods in 17 women with bulimic nervosa (BN) and 17
      women with no history or current symptoms of eating disorders (C). The hypothesis
      that increasing cue salience would be associated with an increase in responsivity
      was tested by comparison of self reported urges, affective responses and
      salivation to the sight and smell (SS) and the sight, smell and taste (SST) of a
      binge/favourite food compared to a neutral stimulus (lettuce leaf). As predicted,
      the BN group reported a greater urge to binge and higher levels of stress/arousal
      to selected binge/favourite food cues compared to the C group. The BN group also
      reported lower confidence to resist the urge to binge and control over food
      intake compared to the C group. Further, a series of planned comparisons in the
      BN group found that the urge to binge, stress, and loss of control were greater
      when participants were exposed to the SST cue than to the SS cue. There was no
      difference between the groups in salivary responsivity to food cues. These
      results are discussed in terms of a conditioning model of cue reactivity.

PMID- 10896759
TI  - Changing food knowledge, food choice, and dietary fiber consumption by using
      tailored messages.
AB  - The aim of this research was to compare the effects of tailored or general
      nutrition messages on individuals' food knowledge, food consumption, and fiber
      intake. Past research in the area of food choice has applied the Theory of
      Reasoned Action or the Theory of Planned Behavior to identify the determinants of
      choice. Neither theory, however, is structured to allow the researcher to examine
      a person's attitudes toward a wide range of foods and then to specify which
      food(s) from among the set of foods to include in a nutrition message. In
      contrast, the Behavioral Alternatives Model (BAM) allows the researcher to
      examine attitudes toward behavioral alternatives (i.e. foods) and to identify
      which foods are most likely to be selected from among a set of foods. We used the
      BAM to specify the foods to include in a tailored nutrition message. The results
      indicated that respondents who received a tailored message derived from the BAM
      had more food-related knowledge and dietary changes in the recommended direction
      than the respondents who received a general message.

PMID- 10896760
TI  - Cephalic phase responses, craving and food intake in normal subjects.
AB  - Cephalic phase responses (CPRs) are elicited during exposure to food cues. They
      gear up the body to optimize digestion or they compensate for unwanted changes
      during a meal. The cue reactivity model of binge eating predicts that CPRs are
      experienced as craving for food, thereby increasing food intake and playing a
      role in abnormal eating behaviour. The present experiment was designed to measure
      CPRs in normal women and to examine its relationship with craving, food intake
      and restraint. Results show that normal subjects do react to food exposure with
      changes in heart rate, heart rate variability (HRV), salivation, blood pressure,
      skin conductance and gastric activity. These CPRs presumably gear up the body and
      presumably do not reflect compensatory responses. Significant correlations
      between restraint and blood pressure, between blood pressure and craving, and
      between craving and food intake were also found. These results are in line with
      the cue reactivity model and suggest that research into physiological CPRs and
      craving in the field of eating disorders is valuable.

PMID- 10896761
TI  - Lipostat in the lean rat: evidence for a non-causal relationship between
      glucocorticoids and leptin levels.
AB  - In order to assess the long-term impact of a complete depletion of
      glucocorticoids on plasma leptin levels, we bilaterally adrenalectomized 20 lean
      rats, and analysed glucocorticoids and leptin levels for 20 consecutive days.
      Results demonstrate that the adrenalectomy (ADX) significantly lowered the leptin
      levels, as compared to sham-operated controls. On the other hand, a significant
      increase in leptin levels was noticeable from day 1 to day 20 of the experiment
      in the sham-operated controls, even though corticosterone levels remained stable
      during that same period. Plasma leptin concentration was proportional to body fat
      content. These results would indicate a non-causal relationship between
      glucocorticoids and leptin levels in the context of a lipostat in the lean rat.

PMID- 10896762
TI  - Emotions and eating in everyday life.
AB  - This field study assessed emotional states experienced in everyday life and
      examined the subjective motivation to eat associated with these emotional states.
      Twenty-three female subjects rated their momentary emotional state and motivation
      to eat on 6 consecutive days at 11:00a.m., 2:00p.m., 5:00p.m., 8:00p.m. and
      11:00p.m. A cluster analysis of the resulting 634 emotion profiles revealed three
      types of emotional states characterized by the labels "Anger-dominance",
      "Tension/Fear" and "Relaxation/Joy". A fourth cluster showing generally low
      levels of emotions was labelled "Unemotional state". Most of the self-rated
      motivations to eat were increased during periods of negative emotions. During
      negative emotions a heightened tendency to cope with these emotions through
      eating and more intense bodily symptoms of hunger were also reported. No
      differences in motivations to eat were found between the two negative emotion
      clusters or between relaxation/joy and the unemotional state. Results indicate
      the presence of "emotionally instrumental eating" in a non-clinical population
      under real life conditions. Physiological correlates of negative emotional states
      may be involved in emotionally instrumental eating.

PMID- 10896763
TI  - Young children's food preferences: a comparison of three modalities of food
      stimuli.
AB  - Food preferences are widely agreed to be important determinants of eating
      behaviour in young children. Existing studies of methods of assessing preferences
      have suggested tasting and ranking foods can generate reliable responses with
      young children, but there have been few attempts to assess other methods which
      might provide a more convenient alternative in situations where the use of real
      foods could be difficult (e.g. outside the laboratory), or tasting could be
      undesirable (e.g. if there are large numbers of foods, or foods which children
      would be unwilling to taste). The present study is a comparison of the
      reliability of preferences measured using: (i) real foods; (ii) food photographs;
      and (iii) food models, in 3 to 5-year-old children. The results showed that the
      tasting method produced good results, replicating existing data from U.S.
      samples. Food photographs came a close second in reliability but food models
      produced unreliable rankings, especially in the youngest group. Five-year-olds
      produced significantly more consistent results than the younger children. These
      results indicate that using real foods as the stimuli produces the most reliable
      taste preferences with children in this young age range, but photographs may
      provide a convenient alternative with adequate reliability.

PMID- 10896764
TI  - Effect of habitual dietary-protein intake on appetite and satiety.
AB  - To investigate whether appetite response to a high-protein test meal varies
      inversely with habitual protein intake, the satiating influence of dietary
      protein was investigated in 14 subjects. Subjects were divided into two groups on
      the basis of habitual protein intake: means of 1.0 g/kg/day (LP) and 1.4 g/kg/day
      (HP). Appetite was assessed in each group following high protein meals (test a).
      A 13-day period of dietary manipulation increased differences in protein intake
      between groups to a mean of 0.75 g/kg/day (LP) and 1.96 g/kg/day (HP) and a
      second satiety test (b) was performed. A third test (c) was performed in the HP
      group after protein intakes were reduced for 2 days to a mean of 0.85 g/kg/day.
      Differences in satiety were most marked, with significant correlations between
      satiety after the three meals and daily protein intake (r=-0.36). LP satiety was
      significantly greater than HP after test b (p=0.025), and approached significance
      when satiety response during LPb was compared with HPc (p=0.07). Results support
      the hypothesis that the satiating effect of dietary protein varies inversely with
      habitual protein intake.

PMID- 10896765
TI  - Drugs of abuse and reward comparison: a brief review.

PMID- 10896766
TI  - Induction of oral tolerance in the primed immune system: influence of antigen
      persistence and adjuvant form.
AB  - Oral tolerance is being promoted as a therapy for autoimmune diseases and
      therefore will need to be functional in a primed immune system. In previous
      studies, we found that although primed mice could be tolerized by feeding
      ovalbumin (OVA), the degree of the tolerance and its effects on individual
      components of the systemic immune response were more limited than that found in
      naive animals. Here we increased the dose and frequency of antigen feeding in an
      attempt to extend the effects of oral tolerance in primed mice and to understand
      why its effects are limited under these conditions. Increasing the amounts of OVA
      fed, up to a single dose of 400 mg, or using multiple feeds of 5 x 5 or 5 x 25 mg
      OVA, did not radically alter the extent of tolerance, with DTH responses, antigen
      specific proliferation, and IL5 and IFN-gamma production still being tolerized,
      but antibody responses remaining generally resistant. The deficient tolerance in
      primed mice could not be overcome by waiting for maximum clonal expansion to wane
      and was not influenced by persistent release of antigen from a depot adjuvant. We
      conclude that the resistance of primed mice to oral tolerance may be due to the
      fact that antigen-experienced T cells may be inherently resistant to induction of
      tolerance, or that the microenvironment of the primed immune system inhibits the
      delivery of tolerogenic signals to antigen-specific T cells.

PMID- 10896767
TI  - Dual role of B cells in mediating innate and acquired immunity to herpes simplex
      virus infections.
AB  - mu-immunoglobulin chain gene targeted B-cell-deficient mice of susceptible BALB/c
      strain and resistant C57B1/6 strain are up to 100- to 1000-fold more susceptible
      to cutaneous infection by herpes simplex virus (HSV) than the respective control
      wild type mice. The effect of the lack of B cells on immunity to HSV infections
      was analyzed and B cells were found to play a dual role in affecting both innate
      and acquired immune responses. Natural antibodies (IgM isotype), reactive with
      HSV have an anti-viral effect in the innate control of primary cutaneous HSV
      infection. B cells can also function as antigen-presenting cells for the
      stimulation of HSV-specific CD4+ T-cell responses. Consequently, CD4+ T cells and
      interferon-gamma responses were found to be significantly impaired in HSV
      infected B-cell-deficient mice compared to that seen in control mice. No
      significant differences were found in natural-killer-cell- or HSV-specific CD8+ T
      cell activity between control and B-cell-deficient mice. Our results imply a role
      for B cell in mediating innate and CD4+ T-cell-specific immunity in determining
      susceptibility to primary HSV infections.

PMID- 10896768
TI  - Autoantigen-responsive T cell clones demonstrate unfocused TCR cross-reactivity
      toward multiple related ligands: implications for autoimmunity.
AB  - It has been suggested that the cross-reaction of a single T cell receptor with
      multiple different peptide ligands is a mechanism for maintaining a diverse yet
      compact immune repertoire. In the context of autoimmune disease it is important
      to understand how this property is balanced against the maintenance of self
      tolerance. Specifically, whether the cross-reactivity inherent in the immune
      system is focused or unfocused will have important consequences for the
      development of autoimmune disease. If cross-reactivity is "focused," then in an
      immune response to a foreign antigen all T cell receptors that recognize the
      foreign antigen will cross-react with a specific autoantigenic peptide. However,
      if cross-reactivity is "unfocused," an immune response to a foreign antigen will
      result in the activation of a small number of self-reactive cells within a larger
      pool of cells specific for the foreign antigen. We have tested whether cross
      reactivity is focused or unfocused by generating a panel of T cell clones that
      respond to two closely related ligands. W144 is an autoantigenic peptide of
      myelin proteolipid protein, PLP 139-151 (HSLGKWLGHPDKF), and Q144 is an altered
      peptide of PLP 139-151 bearing a glutamine for tryptophan substitution at
      position 144. The Q144-responsive clones have a broad degree of cross-reactivity
      with other position 144 substituted peptides. We find that despite their
      characteristic responses to Q144 and W144, the patterns of responses of these
      clones to other structurally related ligands are random, demonstrating that cross
      reactivity is unfocused in the absence of selection. Maintaining a diverse range
      of cross-reactive interactions may limit nonspecific responses to autoantigens.

PMID- 10896769
TI  - IL-10 deficiency does not inhibit insulitis and accelerates cyclophosphamide
      induced diabetes in the nonobese diabetic mouse.
AB  - IL-10 exterts profound immunostimulatory and immunoinhibitory effects. To explore
      the role of IL-10 in autoimmune diabetes of nonobese diabetic (NOD) mice, we
      generated IL-10-deficient NOD mice. In contrast to our previous results with
      neutralizing antibodies to IL-10, IL-10-deficient NOD mice developed insulitis
      and their splenocytes readily responded to islet antigen glutamic acid
      decarboxylase 65. IL-10-deficient NOD mice did not develop accelerated
      spontaneous diabetes. On the other hand, IL-10-deficient NOD mice developed
      accelerated disease following cyclophosphamide (CYP) injection. These findings
      demonstrate that IL-10 is dispensable for autoimmune diabetes. IL-10's absence
      fails to accelerate endogenous diabetes but potentiates CYP-induced diabetes.

PMID- 10896770
TI  - Induction of apoptosis in bacillus Calmette-Guerin-activated T cells by
      transforming growth factor-beta.
AB  - In view of the critical role played by bacillus Calmette-Guerin (BCG) in the
      development and functional activation of protective T cells against tuberculosis,
      it has become important to understand the mechanisms by which cytokines regulate
      BCG-mediated immune responses. There is evidence that cytokine-mediated
      suppression of T cell function by mechanisms, including apoptosis, may reduce
      host resistance in tuberculosis. However, it is unclear whether cytokine-mediated
      suppression of antigen-responsive T cells through apoptotic mechanisms may be
      operating during human cellular activation induced by BCG. Here we present
      evidence, for the first time, that treatment of BCG-activated T cells with
      transforming growth factor-beta (TGF-beta) induces cellular apoptosis. These
      results were further supported by the fact that treatment of cells with a
      blocking mAb directed to TGF-beta significantly inhibited the percentage of
      apoptosis induced by TGF-beta. Interestingly, TGF-beta-mediated death of BCG
      activated T cells in cultures containing interleukin (IL)-12 was observed.
      Moreover, our results demonstrated the induction of apoptosis by TGF-beta in BCG
      activated T cells cultured in the presence of exogenous IL-12. In addition, our
      data indicated that TGF-beta significantly inhibited both BCG-induced cell growth
      determined by thymidine uptake and BCG-induced IFN-gamma secretion. Finally, TGF
      beta-induced apoptosis in BCG-activated T cells correlated inversely with BCG
      induced IFN-gamma secretion. Taken together, these findings indicate that TGF
      beta induces apoptosis in human T cells activated with BCG and at the same time
      suggest that loss of BCG-reactive T cells through apoptotic mechanisms could
      contribute to an increased susceptibility to Mycobacterium tuberculosis
      infection.

PMID- 10896771
TI  - Heroin-induced alterations in leukocyte numbers and apoptosis in the rat spleen.
AB  - The present study assessed the effects of acute heroin treatment on the
      cellularity of the rat spleen and the rate of splenocyte death by necrosis or
      apoptosis. The results showed that 1 h after a single injection of heroin, the
      total number of leukocytes in the spleen was decreased in a dose-dependent
      manner. Prior injection of naltrexone completely blocked heroin's effect, and the
      heroin-induced decrease in splenic leukocytes was not associated with a heroin
      induced increase in circulating leukocytes. A 1-h exposure to heroin did not
      increase levels of lactate dehydrogenase, a cytosolic enzyme, in supernatants of
      splenic mononuclear cells cultured for 45 min or 24 h, suggesting that heroin
      does not increase necrotic death in the spleen. In contrast, a 1-h heroin
      treatment did increase the percentage of Annexin V(+) cells in 0- and 24-h
      cultures of splenic mononuclear cells, indicating that heroin increases apoptotic
      death in the spleen. A 3-h exposure to heroin also produced a significant
      increase in apoptosis in the spleen. DNA fragmentation, a marker of cells in late
      stages of apoptosis, could not be detected in fresh splenocytes, but was evident
      in 24-h cultures of splenic mononuclear cells from saline- and heroin-treated
      rats. These results demonstrate that a single administration of heroin produces a
      decrease in the number of splenic leukocytes and an increase in the apoptotic
      death of splenic mononuclear cells.

PMID- 10896772
TI  - STAT3 regulates the growth and immunoglobulin production of BCL(1) B cell
      lymphoma through control of cell cycle progression.
AB  - STAT3 is constitutively phosphorylated on tyrosine(705) in self-renewing, CD5(+)
      murine B-1 lymphocytes. Nuclear extracts from untreated primary B-1 or CD5(+)
      BCL(1) B lymphoma cells were found to contain immunoreactive STAT3 protein that
      binds to a sis-inducible element present in the promoter of the p21(waf1/cip1)
      tumor suppressor gene and is constitutively phosphorylated on serine(727). To
      determine the functional significance of constitutive STAT3 activation in B
      lymphoma cells, a specific STAT3 antisense oligonucleotide was developed and used
      to examine basal BCL(1) cell growth and IgM production. Abrogating STAT3
      expression in BCL(1) cells inhibited their proliferative capacity and induced a
      corresponding decrease in secretion of IgM. Cell cycle analysis showed a block in
      progression through G1 in BCL(1) cells treated with the STAT3 antisense
      oligonucleotide. These results indicate that STAT3 controls cell growth and
      immunoglobulin secretion by enhancing progression through the G1 phase of the
      cell cycle in BCL(1) B cell lymphoma.

PMID- 10896773
TI  - Potential role of CagA in the inhibition of T cell reactivity in Helicobacter
      pylori infections.
AB  - The pathogenicity of chronic gastroduodenal diseases is very often related to
      Helicobacter pylori infections. Most H. pylori strains carry the cagA gene
      encoding an immunodominant 120- to 128-kDa protein which is considered a
      virulence marker. The majority of CagA-positive H. pylori isolates also produce a
      95-kDa protein cytotoxin (VacA) causing vacuolation and degradation of mammalian
      cells. In our previous study we have shown that live H. pylori bacteria and their
      sonicates inhibit PHA-driven proliferation of human T lymphocytes. The H. pylori
      CagA and VacA proteins were suspected of a paralyzing effect of H. pylori on T
      cell proliferation. In this report, by using isogenic H. pylori mutant strains
      defective in CagA and VacA proteins, we determined that CagA is responsible for
      the inhibition of PHA-induced proliferation of T cells.

PMID- 10896774
TI  - Involvement of the [uPAR:uPA:PAI-1:LRP] complex in human myogenic cell motility.
AB  - The urokinase-type plasminogen activator system is a proteolytic system involved
      in tissue remodeling and cell migration. At the cell surface, receptor (uPAR)
      bound urokinase (uPA) binds its inhibitor PAI-1, localized in the matrix, and the
      complex is internalized by endocytic receptors, such as the low-density
      lipoprotein receptor-related protein (LRP). We previously proposed a
      nonproteolytic role for the uPA system in human myogenic cell differentiation in
      vitro, i.e., cell fusion, and showed that myogenic cells can use PAI-1 as an
      adhesion matrix molecule. The aim of this study was to define the role of the uPA
      system in myogenic cell migration that is necessary for fusion. Using a two
      dimensional motility assay and microcinematography, we showed that any
      interference with the [uPAR:uPA:PAI-1] complex formation, and interference with
      LRP binding to this complex, markedly decreased myogenic cell motility. This
      phenomenon was reversible and independent of plasmin activity. Inhibition of cell
      motility was associated with suppression of both filopodia and membrane ruffling
      activity. [uPAR:uPA:PAI-1:LRP] complex formation involves high-affinity molecular
      interactions and results in quick internalization of the complex. It is likely
      that this complex supports the membrane ruffling activity involved in the
      guidance of the migrating cell toward appropriate sites for attachment.

PMID- 10896775
TI  - Targeted inhibition of wound-induced PAI-1 expression alters migration and
      differentiation in human epidermal keratinocytes.
AB  - In the adult epidermis, keratinocytes do not normally express the type-1
      inhibitor of plasminogen activator (PAI-1). Basal epithelial cell-specific PAI-1
      synthesis, however, accompanies epidermal wound repair in vivo in which PAI-1
      transcripts and immunoreactive protein are confined to epithelial cells in the
      migrating tongue and the hyperproliferative zone. A model system using human
      keratinocytes (HaCaT cells) was developed to assess functional relationships
      between epithelial growth state transitions and PAI-1 expression. PAI-1 synthesis
      was maximal in low population density, exponentially growing HaCaT cultures;
      relative PAI-1 mRNA and protein levels progressively declined as cells attained,
      and were maintained in, a postconfluent condition. While the fraction of PAI-1(+)
      keratinocytes remained stable (at approximately 85-90% of the population)
      throughout the culture period, both PAI-1 mRNA abundance and mean cell-associated
      PAI-1 protein declined by >90% during prolonged (i.e., 8-day) growth arrest.
      Similar to epidermal trauma in vivo, scrape wounding of HaCaT monolayers resulted
      in the rapid and location-specific induction of PAI-1 protein (an increase of 11-
      to 16-fold relative to unwounded cultures) in cells immediately bordering the
      injury site. PAI-1 expression was evident in keratinocytes that comprised the
      opposed migrating fronts and remained elevated until wound closure. Down
      regulation of PAI-1 synthesis in HaCaT cells transfected with an inducible
      LacSwitch-based antisense vector system markedly impaired both the rate and the
      extent of wound closure. All injuries created in antisense PAI-1 monolayers
      remained unhealed at day 8 postinjury compared to the 3-day complete repair
      typical of control cultures. Vector-driven modulation of PAI-1 synthesis was also
      associated with an increase in the percentage of suprabasal-type keratinocytes
      within the wound field. PAI-1 expression by migrating HaCaT cells appears
      necessary to maintain the basal epidermal phenotype and/or appropriate cell-to
      substrate adhesion during injury repair.

PMID- 10896776
TI  - Histone macroH2A1.2 is concentrated in the XY-body by the early pachytene stage
      of spermatogenesis.
AB  - The pairing of sex chromosomes during meiosis in male mammals is associated with
      ongoing heterochromatinization and X inactivation. This process occurs in a
      specific area of the nucleus that can be discerned morphologically: the sex
      vesicle or XY-body. In contrast to X inactivation in the somatic cells of female
      mammals the reasons for X inactivation in the male germline remain obscure. We
      have recently demonstrated that the inactive X chromosome in somatic cells of
      female mammals is marked by a high concentration of histone macroH2A. Here we
      investigate X inactivation in the meiotic cells of the male germline. We
      demonstrate here that macroH2A1.2 is present in the nuclei of germ cells starting
      first with localization that is largely, if not exclusively, to the developing XY
      body in early pachytene spermatocytes. Our results suggest that inactivation of
      sex chromosomes in the male germ cell includes a major alteration of the
      nucleosomal structure.

PMID- 10896777
TI  - Induction of M-phase arrest and apoptosis after HIV-1 Vpr expression through
      uncoupling of nuclear and centrosomal cycle in HeLa cells.
AB  - The human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr induces
      cell cycle arrest in the G2 phase of the cell cycle followed by apoptosis. The
      mechanism of the arrest is unknown but the arrest is believed to facilitate viral
      replication. In the present study, we have established cell lines that allow
      conditional expression of Vpr, and have examined the mechanism of cell death
      following Vpr expression. We found that cells expressing Vpr enter M phase after
      long G2 arrest but formed aberrant multipolar spindles that were incapable of
      completing karyokinesis or cytokinesis. This abnormality provided the basis for
      apoptosis, which always followed in these cells. The multipolar spindles formed
      in response to abnormal centrosomal duplication that occurred during the G2
      arrest but did not occur in cells arrested in G2 by irradiation. Thus, the
      expression of Vpr appears to be responsible for abnormal centrosome duplication,
      which in turn contributes in part to the rapid cell death following HIV-1
      infection.

PMID- 10896778
TI  - Telomerase expression restores dermal integrity to in vitro-aged fibroblasts in a
      reconstituted skin model.
AB  - The lifespan of human fibroblasts and other primary cell strains can be extended
      by expression of the telomerase catalytic subunit (hTERT). Since replicative
      senescence is accompanied by substantial alterations in gene expression, we
      evaluated characteristics of in vitro-aged dermal fibroblast populations before
      and after immortalization with telomerase. The biological behavior of these
      populations was assessed by incorporation into reconstituted human skin.
      Reminiscent of skin in the elderly, we observed increased fragility and
      subepidermal blistering with increased passage number of dermal fibroblasts, but
      the expression of telomerase in late passage populations restored the normal
      nonblistering phenotype. DNA microarray analysis showed that senescent
      fibroblasts express reduced levels of collagen I and III, as well as increased
      levels of a series of markers associated with the destruction of dermal matrix
      and inflammatory processes, and that the expression of telomerase results in mRNA
      expression patterns that are substantially similar to early passage cells. Thus,
      telomerase activity not only confers replicative immortality to skin fibroblasts,
      but can also prevent or reverse the loss of biological function seen in senescent
      cell populations.

PMID- 10896779
TI  - In vivo migration of transplanted myoblasts requires matrix metalloproteinase
      activity.
AB  - Muscle cell migration and extracellular matrix remodeling are essential aspects
      of muscle development and regeneration. In this study, using a new technique to
      assess in vivo myoblast migration, we have confirmed previous results showing
      that the C(2)C(12) myoblast cell line exhibits a higher migratory capacity than
      primary myoblasts. To test the hypothesis that matrix metalloproteinases (MMPs)
      are required for the migration of C(2)C(12) myoblasts, we determined whether a
      synthetic metalloproteinase inhibitor, BB94 (Batimastat), inhibited this process
      in vivo. Pretreatment with BB94 for 3 days decreased the C(2)C(12) migration at 2
      days after cell injection. Since MMP expression is thus necessary for myoblast
      migration, we have undertaken the identification and characterization of the MMPs
      expressed by the C(2)C(12) cell line. An RT-PCR assay was used to determine the
      pattern of MMP mRNA expression by the C(2)C(12) cell line. The proteolytic
      activities of the MMPs secreted in the culture medium were also assessed by
      gelatin zymography. The results showed that MMP2 (gelatinase A, 72-kDa type IV
      collagenase) and MT1-MMP transcripts were expressed by this cell line; however,
      only MMP2 was secreted and was able to be activated in the extracellular
      environment. This cell line failed to express MMP9 (gelatinase B, 92-kDa type IV
      collagenase), stromelysine 2, or stromelysine 3. Our observation that the
      membrane type MMP (MT1-MMP) transcript is also expressed by the C(2)C(12)
      suggests that the MMP2 proform (pro-MMP2), may be activated by the MT1-MMP. This
      possibility is supported by our observation that the pretreatment of C(2)C(12)
      with concanavalin A (which is known to induce the expression of MT1-MMP) resulted
      in the processing of pro-MMP2 to its mature form, in a dose-dependent manner.
      Overexpression and activation of MMP2 in normal myoblasts showed significant
      increased migration of mouse myoblasts in vivo. Our finding that MMP2 and MT1-MMP
      gene are coexpressed by C(2)C(12) myoblasts could account for the high migratory
      capacity of C(2)C(12). Together these results supported the importance of MMP2
      and its activation by MT1-MMP for myoblast migration.

PMID- 10896780
TI  - In vitro replication and differentiation of normal human oral keratinocytes.
AB  - The replication kinetics and cytological changes of normal human oral
      keratinocytes (NHOK) isolated from the basal surface of oral epithelial sheet and
      cultured as dispersed cells in low (0.15 mM) Ca(2+) medium without serum were
      analyzed. Replicating NHOK were quantitated by cell count and identified by
      [(3)H]thymidine uptake. Cell morphology was analyzed by phase contrast and
      transmission electron microscopy, and by cytochemical staining for endogenous
      beta-galactosidase (beta-gal) activity, involucrin, and cytokeratin types 1 and
      10 (K1/K10). Primary NHOK obtained from 15 different donors whose ages ranged
      from 21 to 62 years consistently showed three distinct phases of replication,
      i.e., exponential, senescing, and senescent, which were independent of the
      donors' age. Initially, the cells replicated exponentially for a period of 20
      days with a doubling time of 26.6 +/- 3.5 h. They then gradually entered
      replication arrest over a period of 18 days. The cells underwent a maximum of
      22.1 +/- 2.8 population doublings. The onset of gradual replication arrest
      coincided with an increase in the fraction of cells, which stopped DNA synthesis
      within a maximum of 48 h and which stained for beta-gal. The fraction of
      terminally differentiated cells stained for K1/K10 did not increase until nearly
      all the cells had stopped replicating (senescent phase) and maximal beta-gal
      staining had been reached. Subsequently, the percentage of beta-gal stained cells
      actually decreased while the percentage of those stained for K1/K10 increased to
      a maximum of 80-90% within 2-3 weeks. Exposure of exponentially replicating NHOK
      to 5-aza-2'-deoxycytidine (5-aza CdR) inhibited DNA replication within 18-48 h
      and induced terminal differentiation 6 days later. In contrast, exposure of these
      cells to 1.5 mM Ca(2+) induced expression of involucrin and K1/K10 within 48 h
      without inhibiting DNA synthesis. Thus, replication arrest preceded
      differentiation in NHOK serially subcultured in vitro; however, differentiation
      could be induced without replication arrest.

PMID- 10896781
TI  - CBP1 associates with the Dictyostelium cytoskeleton and is important for normal
      cell aggregation under certain developmental conditions.
AB  - In cells of the eukaryotic microorganism Dictyostelium discoideum, at least eight
      small, four-EF-hand Ca(2+)-binding proteins of unknown function are expressed at
      specific times during development. One of these proteins, calcium-binding protein
      1 (CBP1), first appears just prior to cell aggregation and then is present at
      relatively constant levels throughout development. To determine a role for CBP1
      during development, the protein was used as bait in a yeast two-hybrid screen to
      reveal putative CBP1-interacting proteins. Two proteins identified in this screen
      were the actin-binding proteins, protovillin and EF-1alpha. Using an in vitro
      binding assay, both of these proteins were found to interact with CBP1 in the
      absence of Ca(2+), but the interaction of CBP1 with EF-1alpha was increased
      substantially by Ca(2+). CBP1 was also shown by fluorescence microscopy and by
      binding assays to associate with the actin cytoskeleton of Dictyostelium cells
      during development, and these interactions were partially Ca(2+)-dependent. cbpA
      null cells grew normally, but under certain developmental conditions, cell
      aggregation was prolonged and irregular. This defect in aggregation appeared to
      be related to a general reduction in cell motility rather than to a decrease in
      the ability of the cells to respond to the chemoattractant cAMP. Together, these
      results suggest that CBP1 might function to help regulate the reorganization of
      the Dictyostelium actin cytoskeleton during cell aggregation.

PMID- 10896782
TI  - Genomic convergence and suppression of centrosome hyperamplification in primary
      p53-/- cells in prolonged culture.
AB  - Chromosome instability, a major property of cancer cells, is believed to promote
      mutations that establish malignant phenotypes. Centrosome hyperamplification and
      the consequential increase in the frequency of aberrant mitoses are the major
      causes of chromosome instability in cancer cells that lack the functional p53
      tumor suppressor protein. Here, we examined dynamic changes of chromosome and
      centrosome behaviors during long-term culturing of primary epithelial cells
      derived from p53-null mice. The heterogeneity in the number of chromosomes per
      cell in the early to mid passage cell population diminished in late passage
      cells, giving rise to distinct subpopulations of cells. Concomitantly, centrosome
      hyperamplification that was observed at a high frequency in early to mid passage
      cells was suppressed in late passage cells. These results provide an explanation
      for the frequent observations that some cancer cell lines and tissues that lack
      functional p53 show normal centrosome behaviors and altered, yet relatively
      stable, chromosomes. Moreover, our in vitro findings may provide a model for
      possible genomic convergence in cultured cells. This may be analogous to the
      genomic convergence model proposed for in vivo tumor progression in which
      chromosome instability initially imposed during tumorigenesis becomes suppressed
      when neoplastic cells have acquired chromosome compositions that promise an
      optimal growth in a given environment.

PMID- 10896783
TI  - Retinoic acid-mediated G1 arrest is associated with induction of p27(Kip1) and
      inhibition of cyclin-dependent kinase 3 in human lung squamous carcinoma CH27
      cells.
AB  - Retinoids are promising agents for the prevention and treatment of several human
      malignancies including lung cancer. In this study, the effect of retinoic acid
      (RA) on cell growth and the mechanism of growth modulation were examined in human
      lung squamous carcinoma CH27 cells. Here we report that RA mediated the dose- and
      time-dependent growth arrest in G1 phase, accompanied by the up-regulation of
      p27(Kip1) and the down-regulation of the cyclin-dependent kinase 3 (Cdk3) and
      p21(CIP1/Waf1) proteins. Furthermore, RA-induced growth arrest of CH27 cells was
      also associated with increased retinoic acid receptor beta (RARbeta) and reduced
      c-Myc expression. However, RA had no effect on the levels of cyclins A, D1, D3,
      E, or H, or on Cdk2, Cdk4, Cdk5, CDk6, Cdk7, p16(Ink4A), p15(Ink4B), p53, or pRb
      proteins in CH27 cells. Evaluation of the kinase activity of cyclin-Cdk complexes
      showed that RA increases p27(Kip1) expression in CH27 cells leading to markedly
      reduced cyclin A/Cdk2 kinase activity and slightly reduced cyclin E/Cdk2 kinase
      activity, with no effect on cyclin D/Cdk4 and cyclin D/Cdk6 activities. Moreover,
      coincident with the decrease in kinase activity was a drastic increase in cyclin
      A-bound p27(Kip1). These results suggest that increases in the levels of
      p27(Kip1) and its binding to cyclin A, as well as reduction of Cdk3 protein
      expression, are strong candidates for the cell cycle regulator that prevents the
      entry into the S phase in RA-treated CH27 cells, with prolongation of G1 phase
      and inhibition of DNA synthesis.

PMID- 10896784
TI  - Phosphorylation of the beta1 integrin cytoplasmic domain: toward an understanding
      of function and mechanism.
AB  - As F9 stem cells differentiate into parietal endoderm they form focal adhesion
      sites. There is a concomitant decrease in the level of phosphorylation of S785 in
      the cytoplasmic domain of the beta1 integrin subunit. Previous transfection
      studies demonstrate that site-specific mutations at this residue, mimicking
      different phosphorylation states, can alter the subcellular localization of the
      subunit in differentiating F9 cells. We now extend these observations in an
      attempt to substantiate the function of beta1 phosphorylation and determine how
      the phosphorylation levels are regulated. We show that treatment of parietal
      endoderm with okadaic acid induces an increase in beta1 phosphorylation and
      selective loss of beta1 from focal adhesion sites. Using a PCR approach, we
      identify two phosphatases expressed in parietal endoderm, including PP2A. Using a
      crosslinking approach, where antibodies are added to live cells, we show that the
      catalytic subunit of PP2A co-immunoprecipitates with beta1. Immunocytochemistry
      shows PP2A colocalizing to focal adhesion sites with beta1. In addition integrin
      linked kinase (ILK) co-immunoprecipitates with beta1 in parietal endoderm and
      localizes to focal adhesion sites. Okadaic acid treatment significantly decreases
      the level of ILK associated with beta1. A possible role for regulated beta1
      phosphorylation in cell migration is discussed.

PMID- 10896785
TI  - Analysis of the alpha4beta1 integrin-osteopontin interaction.
AB  - The integrin alpha4beta1 is involved in mediating exfiltration of leukocytes from
      the vasculature. It interacts with a number of proteins up-regulated during the
      inflammatory response including VCAM-1 and the CS-1 alternatively spliced region
      of fibronectin. In addition it binds the multifunctional protein osteopontin
      (OPN), which can act as both a cytokine and an extracellular matrix molecule.
      Here we map the region of human OPN that supports cell adhesion via alpha4beta1
      using GST fusion proteins. We show that alpha4beta1 expressed in J6 cells
      interacts with intact OPN when the integrin is in a high activation state, and by
      deletion mapping that the alpha4beta1 binding region in OPN lies between amino
      acid residues 125 and 168 (aa125-168). This region contains the central RGD motif
      of OPN, which also interacts with integrins alphavbeta3, alphavbeta5,
      alphavbeta1, alpha8beta1, and alpha5beta1. Mutating the RGD motif to RAD had no
      effect on the interaction with alpha4beta1. To define the binding site the region
      incorporating aa125-168 was divided into 5 overlapping peptides expressed as GST
      fusion proteins. Two peptides supported adhesion via alpha4beta1, aa132-146, and
      aa153-168; of these only a synthetic peptide, SVVYGLR (aa162-168), derived from
      aa153-168 was able to inhibit alpha4beta1 binding to CS-1. These data identify
      the motif SVVYGLR as a novel peptide inhibitor of alpha4beta1, and the primary
      alpha4beta1 binding site within OPN.

PMID- 10896786
TI  - Functional characterization of cultured cells derived from an intraepidermal
      carcinoma of the skin (IEC-1).
AB  - We have successfully isolated a cell line (IEC-1) from an intraepidermal
      carcinoma of the skin of a patient and compared its behavior, in vitro, to normal
      human epidermal keratinocytes (HEK) and squamous cell carcinoma cell lines
      (SCCs). HEK differentiation comprises an initial growth arrest followed by an
      induction of squamous differentiation-specific genes such as transglutaminase
      type 1 (TG-1). Using thymidine uptake and TG-1 induction as markers of
      proliferation and differentiation, respectively, we were able to show that HEKs
      and the IEC-1 cells undergo growth arrest and induce TG-1 mRNA expression in
      response to various differentiation-inducing stimuli, while neoplastic SCC cell
      lines did not. However, differentiation in HEKs was an irreversible process
      whereas differentiation of the IEC-1 cells was reversible. Furthermore, growth of
      IEC-1 cells in organotypic raft cultures revealed differences in their ability to
      complete a squamous differentiation program compared with that of normal HEKs.
      The IEC-1 cells also exhibited a transitional phenotype with respect to
      replicative lifespan; HEKs had a lifespan of 4-6 passages, IEC-1 cells of 15-17
      passages, and SCC cells were immortal. These alterations in IEC-1 cell behavior
      were not associated with functional inactivation or mutations of the p53 gene.
      These data indicate that the IEC-1 cells, derived from a preneoplastic skin
      tumor, exhibit differences in their ability to undergo terminal differentiation
      and have an extended replicative lifespan.

PMID- 10896787
TI  - Establishment of SSEA-1- and Oct-4-expressing rat embryonic stem-like cell lines
      and effects of cytokines of the IL-6 family on clonal growth.
AB  - Here, we demonstrate long-term cultivation of alkaline phosphatase-positive rat
      embryonic stem-like (RES) cell lines. RES cells were characterized by their
      typical growth in highly compacted cell clusters, which were found to be
      sensitive against enzymatic dissociation. RES cells expressed stage-specific
      embryonic antigen-1 (SSEA-1) and transcription factor Oct-4, but Oct-4 mRNA was
      detected at lower levels compared to mouse ES cells. Once established to tissue
      culture, RES cells were able to grow in the absence of feeder cells under clonal
      conditions. Cytokines of the interleukin-6 family known to maintain the
      undifferentiated state of mouse ES cells were comparatively analyzed for their
      capacity to maintain the undifferentiated growth of two cell lines, RES-1 and RES
      15, in a clonal assay. Rat ciliary neurotrophic factor (rCNTF), human oncostatin
      M (hOSM), and interleukin-6 and soluble interleukin-6 receptor (IL-6/sIL-6R) were
      found to support clonal growth of RES cells, but the cytokines did not reach the
      efficiency of the colony forming ability of leukemia inhibitory factor (LIF).
      When RES-1 and RES-15 cells were cultivated without feeder cells, SSEA-1
      expression was maintained after clonal growth in the presence of LIF and LIF +
      rCNTF, respectively. Oct-4 mRNA was significantly detected in RES-15 cells when
      cultivated in the absence of feeder cells in media substituted by LIF and/or IL
      6/sIL-6R, as well as without cytokines. In summary, rat embryonic stem-like cell
      lines could be established from rat blastocysts and were able to proliferate as
      undifferentiated alkaline phosphatase-positive cells. Embryonal stem cell
      properties, such as SSEA-1 and Oct-4 expression, were maintained by members of
      the IL-6 family of cytokines, but most significantly by LIF.

PMID- 10896788
TI  - Modulation of endogenous Smad expression in normal skin fibroblasts by
      transforming growth factor-beta.
AB  - Transforming growth factor-beta (TGF-beta) stimulation of collagen synthesis
      plays a fundamental role in physiological tissue repair as well as pathological
      fibrosis. Members of the SMAD family of intracellular proteins are phosphorylated
      by TGF-beta receptors and convey signals to specific TGF-beta-inducible genes.
      Ligand binding initiates signaling through the SMAD pathway, but it is unknown
      how signaling is terminated. The expression and regulation of Smads have been
      characterized mostly in transformed cells using transient expression systems. In
      this study, we investigated the physiological regulation of endogenous Smads by
      TGF-beta in nontransformed normal skin fibroblasts in vitro. Treatment with TGF
      beta resulted in time- and dose-dependent translocation of SMAD3 and SMAD4 from
      the cytoplasm to the nucleus. The levels of SMAD3 and Smad3 mRNA were profoundly
      down-regulated by TGF-beta1 or TGF-beta3 in a time-dependent manner, whereas
      expression of antagonistic Smad7 was rapidly and transiently induced. The
      stability of Smad3 mRNA transcripts was unaffected by TGF-beta. Cycloheximide
      prevented the inhibition of Smad3, but not the induction of Smad7, mRNA
      expression by TGF-beta1, identifying Smad7 as an immediate-early gene target of
      TGF-beta in fibroblasts. In Smad4-deficient breast cancer cells, TGF-beta failed
      to modulate Smad expression, suggesting that SMADs mediate their own regulation
      in response to ligand. These results demonstrate that TGF-beta not only triggers
      functional activation of the SMAD signaling cascade in primary skin fibroblasts,
      but also simultaneously exerts potent effects on endogenous SMAD expression and
      intracellular trafficking. Taken together with recent reports implicating
      ubiquitination in SMAD turnover, these findings indicate the existence of
      multiple levels of control for modulating SMAD-mediated TGF-beta signaling in
      fibroblasts.

PMID- 10896789
TI  - Posttranscriptional stimulation of endothelial cell matrix metalloproteinases 2
      and 1 by endothelioma cells.
AB  - Matrix metalloproteinases (MMPs) play a critical role in the development of
      hemangioma-like vascular tumors in mice injected with murine eEnd.1 endothelioma
      cells. The current study was designed to (a) characterize the presence of MMPs in
      the vascular tumor, (b) define whether these MMPs originate from the transformed
      cells or from the recruited stromal cells and (c) study the stimulatory effect of
      eEnd.1 cells on the production of MMPs by endothelial cells. Several gelatinases
      were present in the eEnd.1 tumor extract, including latent and activated MMP-2
      (72-kDa gelatinase A, EC 3.4.24. 24) and MMP-9 (92-kDa gelatinase B, EC
      3.4.24.35). Immunohistochemical analysis of the tumor revealed focal reactivity
      for MMP-2. No gelatinase was produced by cultured eEnd.1 cells, or by six of nine
      related endothelioma cell lines, suggesting that stroma cells, particularly
      endothelial cells recruited by the tumor cells, rather than eEnd.1 cells
      themselves, are the source of the gelatinases observed in the tumors in vivo. The
      conditioned medium of eEnd.1 cells stimulated the release of MMP-2 and MMP-1
      (interstitial collagenase, EC 3.4.24.7) by endothelial cells, but not of the
      inhibitor TIMP-2. The increased production of MMP-2 and MMP-1, observed at the
      protein level (zymogram and Western blot analysis), occurred through a
      posttranscriptional mechanism, since no increase in mRNA was observed and the
      stimulation was not prevented by inhibitors of protein synthesis. The inhibitory
      effects of monensin and brefeldin A, inhibitors of protein secretion, and the
      decrease in cell-associated MMP-2 in stimulated endothelial cells indicated that
      regulation occurred mostly at the level of protease secretion. MMPs are known to
      be regulated at different levels; this study indicates that, in endothelial
      cells, the stimulation of MMPs can also occur at the level of secretion, a
      mechanism that provides a rapid mobilization of these crucial enzymes in the
      early phases of angiogenesis.

PMID- 10896790
TI  - Species-divergent regulation of human and mouse osteocalcin genes by calciotropic
      hormones.
AB  - Although osteocalcin is the most abundant noncollagenous protein in bone, its
      role remains undefined. Recent studies have reported diametrically opposing
      responses in the vitamin D regulation of the mouse vs the human and rat
      osteocalcin genes. The aim of this study was to increase the understanding of
      these differences and further elucidate the physiological function and regulation
      of osteocalcin. Direct comparison of the regulation of both the endogenous mouse
      osteocalcin gene (mOC) and a human osteocalcin promoter-chloramphenicol acetyl
      transferase (hOC-CAT) reporter as integrated templates was undertaken in primary
      osteoblastic cultures from OSCAT transgenic mice. Expression of both genes was up
      regulated with the onset of mineralization. Long-term chronic 1, 25
      dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) treatment and acute (2 day) PTH
      treatment inhibited both mOC and hOC-CAT expression. At all stages of
      osteoblastic development studied, hOC-CAT was up-regulated by acute 1,25
      (OH)(2)D(3), whereas mOC was unaffected or inhibited. Mouse osteopontin was
      strongly up-regulated by acute 1, 25-(OH)(2)D(3) treatment. Thus, the divergence
      of the osteocalcin responses to 1,25-(OH)(2)D(3) is specific for the osteocalcin
      gene and for an acute 1,25-(OH)(2)D(3) treatment regime. Elucidation of this
      unique aspect of bone physiology will provide valuable insights into the still
      incompletely understood roles of osteocalcin and 1, 25-(OH)(2)D(3) in bone.

PMID- 10896791
TI  - Calcium and calmodulin are essential for Ras-GRF1-mediated activation of the Ras
      pathway by lysophosphatidic acid.
AB  - The exchange factor Ras-GRF1, also called CDC25Mm, couples calcium signaling and
      G-protein-coupled receptors to Ras and downstream effectors. Here we show that
      when expressed in different cell lines Ras-GRF1 strongly enhances the level of
      active Ras (Ras-GTP) and the activity of mitogen-activated protein kinases
      (MAPK). Moreover, in NIH 3T3 fibroblasts it potentiates the effect of
      lysophosphatidic acid (LPA) on Ras protein and MAPK activity. Calmodulin and
      cytosolic free calcium are essential for Ras and MAPK activation induced by LPA
      and mediated by Ras-GRF1, as shown by the finding that BAPTA-AM, an intracellular
      calcium chelator, and calmodulin inhibitors completely abolished this effect.
      This report demonstrates the relevance of calmodulin in addition to calcium for
      the response of Ras-GRF1 to LPA.

PMID- 10896793
TI  - The effect of a monoclonal antibody coupled to ricin A chain-derived peptides on
      endothelial cells in vitro: insights into toxin-mediated vascular damage.
AB  - Immunotoxins (ITs) containing plant or bacterial toxins have a dose-limiting
      toxicity of vascular leak syndrome (VLS) in humans. The active A chain of ricin
      toxin (RTA), other toxins, ribosome-inactivating proteins, and the VLS-inducing
      cytokine IL-2 contain the conserved sequence motif (x)D(y) where x = L, I, G, or
      V and y = V, L, or S. RTA-derived LDV-containing peptides attached to a
      monoclonal antibody, RFB4, induce endothelial cell (EC) damage in vitro and
      vascular leak in two animal models in vivo. We have now investigated the
      mechanism(s) by which this occurs and have found that (1) the exposed D75 in the
      LDV sequence in RTA and the C-terminal flanking threonine play critical roles in
      the ability of RFB4-conjugated RTA peptide to bind to and damage ECs and (2) the
      LDV sequence in RTA induces early manifestations of apoptosis in HUVECs by
      activating caspase-3. These data suggest that RTA-mediated inhibition of protein
      synthesis (due to its active site) and apoptosis (due to LDV) may be mediated by
      different portions of the RTA molecule. These results suggest that ITs prepared
      with RTA mutants containing alterations in LDVT may kill tumor cells in vivo in
      the absence of EC-mediated VLS.

PMID- 10896792
TI  - The regulation of PGE(2) biosynthesis in MG-63 osteosarcoma cells by IL-1 and FGF
      is cell density-dependent.
AB  - We investigated the molecular mechanisms by which treatment of the human
      osteoblast-like cell line MG-63 with interleukin 1beta (IL-1) and/or fibroblast
      growth factor 1 (FGF-1) elicited prostaglandin biosynthesis. IL-1 induced a 5
      fold increase in PGE(2) production compared to controls. While treatment with FGF
      1 alone did not affect PGE(2) biosynthesis, it enhanced the formation of PGE(2)
      by IL-1 by an additional 3- to 5-fold. IL-1-induced PGE(2) biosynthesis
      accompanied increases in steady-state levels of mRNAs encoding cPLA(2) (10- to 15
      fold) and PGHS-2 (>3-fold) and concomitant increases in cPLA(2) protein (>3-fold)
      and PGHS-2 protein (>1. 5-fold). FGF-1 treatment did not affect PGHS-2 gene
      expression, but enhanced the effect of IL-1 on PGHS-2 expression by an additional
      2- to 3-fold. FGF-1 alone enhanced cPLA(2) expression (5-fold), and the combined
      effects of FGF-1 and IL-1 on cPLA(2) expression were additive. There was no
      measurable effect of either agonist on PGHS-1 expression. We also discovered that
      induction of PGE(2) biosynthesis in response to IL-1 or IL-1/FGF-1 was affected
      by the density of MG-63 cells in culture. Subconfluent cultures displayed a 3- to
      10-fold greater response to IL-1 or IL-1/FGF-1 than confluent cultures. The
      decreased PGE(2) induction by IL-1 in confluent cultures was associated with
      reduced IL-1 receptor expression. We conclude that the signaling pathways
      resulting in PGE(2) biosynthesis in response to proinflammatory agents like IL-1
      are subject to complex regulation by additional soluble mediators as well as cell
      cell or cell-extracellular matrix interactions.

PMID- 10896794
TI  - Inhibition of p38 MAP kinase activity up-regulates multiple MAP kinase pathways
      and potentiates 1,25-dihydroxyvitamin D(3)-induced differentiation of human
      leukemia HL60 cells.
AB  - Differentiation therapy for neoplastic diseases has potential for supplementing
      existing treatment modalities but its implementation has been slow. One of the
      reasons is the lack of full understanding of the complexities of cellular
      pathways through which signals for differentiation lead to cell maturation. This
      was addressed in this study using HL60 cells, a well-established model of
      differentiation of neoplastic cells. SB 203580 and SB 202190, specific inhibitors
      of a signaling protein p38 MAP kinase, were found to markedly accelerate
      monocytic differentiation of HL60 cells induced by low concentrations of 1,25
      dihydroxyvitamin D(3) (1,25D(3)). Surprisingly, inhibition of p38 activity
      resulted in sustained enhancement of p38 phosphorylation and of its in vitro
      activity in the absence of the inhibitor, indicating up-regulation of the
      upstream components of the p38 pathway. In addition, SB 203580 or SB 202190
      treatment of HL60 cells resulted in a prolonged activation of the JNK and, to a
      lesser extent, the ERK pathways. The data are consistent with the hypothesis that
      in HL60 cells an interruption of a negative feedback loop from a p38 target
      activates a common regulator of multiple MAPK pathways. The possibility also
      exists that JNK and/or ERK pathways amplify a differentiation signal provided by
      1,25D(3).

PMID- 10896795
TI  - Surgical site infection surveillance.
AB  - Surgical site infection (SSI) is the third most commonly reported nosocomial
      infection and accounts for 14-16% of all nosocomial infections among hospital
      inpatients. A successful SSI surveillance programme includes standardized
      definitions of infection, effective surveillance methods and stratification of
      the SSI rates according to risk factors associated with the development of SSI.
      Surveillance with feedback of information to surgeons and other relevant staff
      has been shown to be an important element in the overall strategy to reduce the
      numbers of SSIs. This paper examines the essential components of a SSI
      surveillance system including surveillance methods, data collection and handling,
      analysis and presentation of results to clinical staff.

PMID- 10896796
TI  - Selective decontamination of the digestive tract: a life saver.
AB  - Selective decontamination of the digestive tract (SDD), a strategy designed to
      prevent or minimize the impact of infection by potentially pathogenic micro
      organisms in critically ill patients requiring long-term mechanical ventilation,
      comprises four component protocols, aiming to control the three types of
      infection occurring in such cases: (i) a parenteral antibiotic, cefotaxime,
      administered for a few days to prevent primary endogenous infections typically
      occurring 'early'; (ii) the topical antimicrobials polymyxin E, tobramycin and
      amphotericin B employed throughout the stay in the intensive care unit to prevent
      secondary endogenous infections tending to develop 'late'; (iii) a high standard
      of hygiene to prevent exogenous infections that may occur throughout the stay in
      the intensive care unit; (iv) surveillance samples of throat and rectum to
      distinguish between these three types of infection, to monitor the compliance and
      the efficacy of the treatment, and to detect the emergence of resistance at an
      early stage. A recent, rigorous, meta-analysis examining 33 randomized SDD trials
      involving 5727 patients demonstrated a significant reduction in overall mortality
      (20%) and in the incidence of respiratory tract infections (65%); conclusive
      evidence that SDD saves the lives of critically ill patients and confirmation
      that SDD is now an evidence based medicine manoeuvre. This same meta-analysis
      found no instance of the emergence of resistance or of associated superinfections
      and/or outbreaks in any of the 33 studies during a period extending upwards of 10
      years. By the criterion of cost-per-survivor, four recent randomized trials
      showed that patient survival is improved more cheaply by employing SDD than by
      the traditional approaches.

PMID- 10896797
TI  - A prospective study on factors influencing aspergillus spore load in the air
      during renovation works in a neonatal intensive care unit.
AB  - The relationship between air contamination (cfu/m(3)) with fungal spores,
      especially Aspergillus spp., in three renovation areas of a neonatal intensive
      care unit (NICU) and colonization and infection rates in a high care area (HC)
      equipped with high efficiency particulate air (HEPA) filtration and a high
      pressure system, was evaluated. Data on the type and site of renovation works,
      outdoor meteorological conditions, patient crowding and nasopharyngeal
      colonization rate were collected. Factors not associated with Aspergillus spp.
      concentration were outdoor temperature, air pressure, wind speed, humidity,
      rainfall, patient density in the NICU, renovation works in the administrative
      area and in the isolation rooms. Multivariate analysis revealed that renovation
      works and air concentration of Aspergillus spp. spores in the medium care area
      (MC) resulted in a significant increase of the concentration in the HC of the
      NICU. The use of a mobile HEPA air filtration system (MedicCleanAir(R)Forte,
      Willebroek, Belgium) caused a significant decrease in the Aspergillus spp.
      concentration. There was no relationship between Aspergillus spp. air
      concentration and nasopharyngeal colonization in the neonates. Invasive
      aspergillosis did not occur during the renovation. This study highlights the
      importance of optimal physical barriers and air filtration to decrease airborne
      fungal spores in high-risk units during renovation works. The value of patient
      surveillance and environmental air sampling is questionable since no relationship
      was found between air contamination and colonization in patients.

PMID- 10896798
TI  - The in-vitro activity of povidone-iodinecream against Staphylococcus aureus and
      its bioavailability in nasal secretions.
AB  - Due to the emergence of mupirocin-resistance in some epidemic strains of
      methicillin resistant Staphylococcus aureus (EMRSA) and the appearance of EMRSA
      with intermediate resistance to vancomycin, we evaluated the in-vitro activity of
      5% povidone-iodine ('Betadine') cream as a possiblealternative to mupirocin for
      the elimination of nasal carriage of S. aureus. As judged by enrichment culture,
      povidone-iodine was bactericidal against three mupirocin-sensitive strains of S.
      aureus from nasal carriers, and against mupirocin-resistant and -sensitive
      strains of EMRSA types 3, 15 and 16, after incubation with povidone-iodine for
      1.0 min at 32 degrees C. Mupirocin nasal ointment did not prevent growth after
      180 min incubation. In a quantitative suspension test, 1:100 dilution of povidone
      iodine cream completely eliminated an inoculum of 10(8)cfu/mL of all nine test
      organisms after incubation at 32 degrees C for 1.0 min, and 1:1000 dilution
      reduced cfu, by a factor of 10(5). After direct inoculation of the povidone
      iodine cream to give 10(5)cfu/g, none of the test strains were recoverable after
      30 s, giving a killing rate of approximately 10(4)cfu/s; for mupirocin nasal
      ointment, the maximum reduction of mupirocin-sensitive strains was ten fold after
      3 h. Povidone-iodine activity was not detectable in sensitivity-testing agar,
      although 0.025% of povidone-iodine was detectable in a 15% nutrient strength
      tryptone soya agar. Using this minimal medium, the addition of nasal secretions
      (from any of 11 samples) reduced the activity of povidone-iodine by 80-90%, but
      mupirocin activity was unaffected. One millilitre of nasal secretions inactivated
      the equivalent of approximately 22.5 mg of povidone-iodine. These results suggest
      that povidone-iodine cream may have a role in the prevention of colonization and
      infection caused by MRSA, including mupirocin-resistant strains.

PMID- 10896799
TI  - Risk factors for colonization with methicillin-resistant Staphylococcus aureus
      among nursing home residents.
AB  - Risk factors predictive of methicillin-resistant Staphylococcus aureus (MRSA)
      colonization in 786 of 910 nursing home residents were evaluated. A customized
      questionnaire was completed by theresidents, who were screened for MRSA. The risk
      factors significantly associated with MRSA colonization were male sex, age >80
      years, residence in the nursing home for <six months, hospitalization during the
      previous 6 months, peripheral vascular disease, pressure sores, steroid therapy,
      poor general skin condition, antibiotic therapy during the previous three months
      and a mental test score of O14. Multivariate analysis identified male sex and
      pressure sores as independent variables.

PMID- 10896800
TI  - Incidence, risk factors and outcome of infection in a 1-year hysterectomy cohort:
      a prospective follow-up study.
AB  - A prospective study was performed following 687 patients who underwent abdominal,
      vaginal and laparoscopic hysterectomy for benign conditions in Turku University
      Hospital. This study evaluates and compares infection after hysterectomy and
      determines risk factors associated with postoperative infection. Infective
      episodes were recorded during hospital stay, convalescence for 4 to 6 weeks at
      home and for 1 year of follow-up. Factors found to be statistically significant
      for hospital-acquired infection on univariate analysis were subsequently assessed
      by means of multivariate analysis. During the hospital stay 23.7% of the study
      population became infected, 38.1% after vaginal hysterectomy, 23.4% after
      abdominal hysterectomy and 3.0% after laparoscopic hysterectomy. Over half of all
      hospital-acquired infections were lower urinary tract infections. Infection
      during convalescence occurred in 19.2% of patients: 29.5% in the vaginal
      hysterectomy group, 17.4% in the abdominal hysterectomy group and 16.7% in the
      laparoscopic hysterectomy group. One year of follow-up did not find any infection
      directly attributable to surgery. Five factors were found to be related to in
      hospital infection on multivariate analysis. These were lack of antibiotic
      prophylaxis, blood loss during operation, intermittent catheterization, anaemia
      and medication for urinary or bowel dysfunction after operation.

PMID- 10896801
TI  - Identification of the bacteriologicalcontamination of a water treatment line used
      for haemodialysis and its disinfection.
AB  - Renal haemodialysis care units in hospitals use enormous amounts of potable water
      for the functioning of 'artificial kidneys'. In order to avoid complications with
      patients' blood this water has to be specially treated. However, the treatment
      line itself can induce problems due to a high concentration of bacteria in the
      water. A high bacterial load, as well as bacterial toxins, can provoke
      immunological reactions in the patients. This paper shows that a granular
      activated carbon (GAC) filter is a source of bacterial contamination of the water
      due to the presence of a biofilm on the medium's surface. The majority of the
      bacteria released are Gram-negative. Because sloughing events in the biofilm can
      lead to dangerously high concentrations of bacteria and endotoxin levels in
      water, it is important to control this phenomenon. In treatment lines, GAC
      filters are regularly chlorinated. Our pilot experiment studied the disinfection
      of the filter with sodium hypochlorite and peracetic acid. Our results show that
      both disinfectants have a weak and transient effect on the biomass in the filter.
      It appears that chemical treatment of the filter is not the ideal solution to the
      bacteriological threat. Moreover, disinfection of the GAC filter transiently
      increases the contamination of the water. Alternative solutions to the use of
      chemical disinfection procedures are discussed.

PMID- 10896802
TI  - High level of recovery of fungi from water and dialysate in haemodialysis units.
AB  - The counts of yeasts and filamentous fungi were investigated in the municipal
      water supplies of haemodialysis centres, in the treated water and the dialysate
      from all 85 haemodialysis units in Greece, in order to estimate their occurrence,
      their correlation with contamination indicator bacteria and other influencing
      factors. Filamentous fungi and yeasts were isolated from 69 (81.2%) and from
      three (3.5%) feed water samples, from 74 (87.1%) and seven (8.2%) treated water
      samples and from 66 (77.7%) and 11 (12.9%) dialysate samples respectively.
      Aspergillus spp and Penicillium spp were the most frequent moulds, while Candida
      spp were the prevailing yeasts. The occurrence of yeasts was significantly higher
      in dialysate than in tap water samples. Counts of filamentous fungi in all 255
      samples were significantly correlated with the counts of total heterotrophic
      bacteria and enterococci, whereas the counts of yeasts were correlated with
      faecal coliforms, total heterotrophic bacteria, as well as enterococci,
      Pseudomonas spp and total coliforms, while no correlation was detected with the
      age of either haemodialysis units, the age of water treatment system, the number
      of artificial kidney machines or the components of the water purification system.
      High recovery of fungi from haemodialysis aqueous environments implies a
      potential risk for haemodialysis patients and indicates the need for continuous
      maintenance and monitoring.

PMID- 10896803
TI  - Better environmental survival of outbreak vs. sporadic MRSA isolates.
AB  - Environmental sources have been associated with prolonged epidemics of
      methicillin-resistant Staphylococcus aureus (MRSA). Our objective was to evaluate
      whether outbreak MRSA strains differ in their environmental survival from
      sporadic MRSA strains. The strains were detected in five adult patients
      unknowingly colonized by MRSA. The MRSA strains from patients No. 1 (phage
      pattern; III-29) and No. 2 (III-215) caused extensive outbreaks in our hospital.
      Contact tracing after detection of the different MRSA strains in the three other
      patients did not reveal further spread. Suspensions of MRSA with and without
      added hospital dust were made in sterile PBS. Surviving counts of MRSA were made
      by culture at two-weekly or longer intervals up to approximately one year. For
      each MRSA strain the ultimate day of viability was ascertained. The environmental
      survival patterns of the five MRSA strains showed qualitative and quantitative
      differences between the two outbreak and three sporadic strains. A gradual
      decline was noted for all strains. All survived longer than 6 months, but the two
      outbreak strains survived significantly better (P<0.01), i.e. in higher
      quantities (circa 1000-fold) and for a 1-3 months longer period. The survival
      patterns of the MRSA strains with and without added dust were similar.

PMID- 10896804
TI  - The rise of Clostridium difficile: the effect of length of stay, patient age and
      antibiotic use.
AB  - Hospitals in the UK have recently seen a marked increase in C. difficile for
      reasons which are unclear. Reduced standards of hygiene, increasingly elderly
      patients, greater cephalosporin use and longer hospital stay have been suggested.
      We retrospectively studied all cases of C. difficile diarrhoea at Princess
      Margaret Hospital, Swindon, over two years. Cephalosporins, patient age and LOS
      appeared unrelated to the rise in C. difficile; penicillins and macrolides were
      related. Our policy of using amoxycillin and clarithromycin for community
      acquired pneumonia coincided with this study and may explain the observed rise in
      C. difficile.

PMID- 10896805
TI  - Outbreak of human parvovirus B19 in hospital workers.
AB  - We report an outbreak of human parvovirus B19 (HPV B19) infection affecting five
      nursing staff, four hospital office workers and one physiotherapist and its
      possible transmission between hospital staff. We investigated the presence of the
      virus in serum specimens using a nested PCR assay to confirm HPV B19 infection.
      The viral genome was detected in serum specimens from a nurse with a rash and
      arthralgia and from three hospital office workers with a febrile illness. The DNA
      sequence of the PCR products from three staff members was identical. Our findings
      suggest that transmission of HPV B19 between hospital staff members occurred.

PMID- 10896806
TI  - Serratia marcescens causing hospital-acquired lower respiratory tract infection.

PMID- 10896807
TI  - Genotypic similarities among themethicillin-resistant Staphylococcus aureus
      isolates recovered from stools, the respiratory tract and other sites in 20
      patients.

PMID- 10896808
TI  - Handwashing and clinical examinations.

PMID- 10896809
TI  - Handwashing: unanswered questions and compliance.

PMID- 10896810
TI  - An Australasian test of the recent African origin theory using the WLH-50
      calvarium.
AB  - This analysis investigates the ancestry of a single modern human specimen from
      Australia, WLH-50 (Thorne et al., in preparation; Webb, 1989). Evaluating its
      ancestry is important to our understanding of modern human origins in Australasia
      because the prevailing models of human origins make different predictions for the
      ancestry of this specimen, and others like it. Some authors believe in the
      validity of a complete replacement theory and propose that modern humans in
      Australasia descended solely from earlier modern human populations found in Late
      Pleistocene Africa and the Levant. These ancestral modern populations are
      believed to have completely replaced other archaic human populations, including
      the Ngandong hominids of Indonesia. According to this recent African origin
      theory, the archaic humans from Indonesia are classified as Homo erectus, a
      different evolutionary species that could not have contributed to the ancestry of
      modern Australasians. Therefore this theory of complete replacement makes clear
      predictions concerning the ancestry of the specimen WLH-50. We tested these
      predictions using two methods: a discriminant analysis of metric data for three
      samples that are potential ancestors of WLH-50 (Ngandong, Late Pleistocene
      Africans, Levant hominids from Skhul and Qafzeh) and a pairwise difference
      analysis of nonmetric data for individuals within these samples. The results of
      these procedures provide an unambiguous refutation of a model of complete
      replacement within this region, and indicate that the Ngandong hominids or a
      population like them may have contributed significantly to the ancestry of WLH
      50. We therefore contend that Ngandong hominids should be classified within the
      evolutionary species, Homo sapiens. The Multiregional model of human evolution
      has the expectation that Australasian ancestry is in all three of the potentially
      ancestral groups and best explains modern Australasian origins.

PMID- 10896811
TI  - Temporal trends and metric variation in the mandibles and dentition of
      Australopithecus afarensis.
AB  - The Pliocene hominin samples from Hadar and Laetoli are thought to represent one
      species, Australopithecus afarensis, that exhibits stasis throughout its temporal
      range and has high levels of skeletal sexual dimorphism. In this paper, we test
      the hypothesis of stasis in dental and mandibular dimensions using nonparametric
      rank correlation methods to detect temporal trends and randomization tests to
      evaluate their statistical significance. We then use two methods (CV resampling;
      Fligner-Killeen test) to compare overall levels of variation in the fossil sample
      to those of extant hominoid species. Together, these analyses allow us to gauge
      the effects of changes through time on variation in mandibles and teeth of A.
      afarensis.P(3)mesiodistal length, M(3)size, and canine shape change through time
      but do not appear unusually variable in the sample as a whole. These temporal
      trends possibly reflect differences between the Laetoli and Hadar site-samples.
      For mandibles, a pronounced trend towards greater corpus size occurs late in the
      temporal sequence and contributes to high levels of variation compared to African
      apes. These results show that significant directional changes do occur in the A.
      afarensis mandibles and teeth, and in these elements, at least, the species is
      not static. Temporal variation is clearly an important component of overall
      variation in the A. afarensis lineage, even though other factors, such as sexual
      dimorphism, may also play a part.

PMID- 10896812
TI  - The evolution of human skin coloration.
AB  - Skin color is one of the most conspicuous ways in which humans vary and has been
      widely used to define human races. Here we present new evidence indicating that
      variations in skin color are adaptive, and are related to the regulation of
      ultraviolet (UV) radiation penetration in the integument and its direct and
      indirect effects on fitness. Using remotely sensed data on UV radiation levels,
      hypotheses concerning the distribution of the skin colors of indigenous peoples
      relative to UV levels were tested quantitatively in this study for the first
      time. The major results of this study are: (1) skin reflectance is strongly
      correlated with absolute latitude and UV radiation levels. The highest
      correlation between skin reflectance and UV levels was observed at 545 nm, near
      the absorption maximum for oxyhemoglobin, suggesting that the main role of
      melanin pigmentation in humans is regulation of the effects of UV radiation on
      the contents of cutaneous blood vessels located in the dermis. (2) Predicted skin
      reflectances deviated little from observed values. (3) In all populations for
      which skin reflectance data were available for males and females, females were
      found to be lighter skinned than males. (4) The clinal gradation of skin
      coloration observed among indigenous peoples is correlated with UV radiation
      levels and represents a compromise solution to the conflicting physiological
      requirements of photoprotection and vitamin D synthesis. The earliest members of
      the hominid lineage probably had a mostly unpigmented or lightly pigmented
      integument covered with dark black hair, similar to that of the modern
      chimpanzee. The evolution of a naked, darkly pigmented integument occurred early
      in the evolution of the genus Homo. A dark epidermis protected sweat glands from
      UV-induced injury, thus insuring the integrity of somatic thermoregulation. Of
      greater significance to individual reproductive success was that highly melanized
      skin protected against UV-induced photolysis of folate (Branda & Eaton, 1978,
      Science201, 625-626; Jablonski, 1992, Proc. Australas. Soc. Hum. Biol.5, 455-462,
      1999, Med. Hypotheses52, 581-582), a metabolite essential for normal development
      of the embryonic neural tube (Bower & Stanley, 1989, The Medical Journal of
      Australia150, 613-619; Medical Research Council Vitamin Research Group, 1991, The
      Lancet338, 31-37) and spermatogenesis (Cosentino et al., 1990, Proc. Natn. Acad.
      Sci. U.S.A.87, 1431-1435; Mathur et al., 1977, Fertility Sterility28, 1356
      1360).As hominids migrated outside of the tropics, varying degrees of
      depigmentation evolved in order to permit UVB-induced synthesis of previtamin
      D(3). The lighter color of female skin may be required to permit synthesis of the
      relatively higher amounts of vitamin D(3)necessary during pregnancy and
      lactation. Skin coloration in humans is adaptive and labile. Skin pigmentation
      levels have changed more than once in human evolution. Because of this, skin
      coloration is of no value in determining phylogenetic relationships among modern
      human groups.

PMID- 10896813
TI  - Elliptical fourier analysis of symphyseal shape in great ape mandibles.
AB  - The midsagittal profile of the mandibular symphysis has served as both a
      taxonomic marker and a phylogenetically salient character in debates over
      hominoid evolution. Nevertheless, the utility of symphyseal shape as an
      informative attribute for paleobiological reconstructions is suspect.
      Quantification of shape variation has proven to be particularly problematic; it
      has long been recognized that conventional linear measurements (and the indices
      derived from them), while replicable, summarize aspects of shape very poorly
      because of the vast amount of contour information that is lost in the process. In
      this study, a type of Fourier analysis is applied to cross-sectional contours of
      ape mandibles in order to provide a mathematical accounting of shape variation in
      a "global" sense; that is, by applying the "totality" of contour information in a
      comparative analysis. Shape variation in the mandibular symphysis is explored
      through the decomposition of coordinate data into elliptical Fourier
      coefficients. These coefficients are used to compute average taxonomic distances
      (ATD) among individuals of chimpanzees, gorillas, and orang-utans. The resulting
      shape-based distances are summarized via clustering (UPGMA) and ordination
      (principal coordinates analysis-PCO). Principal coordinate scores are subjected
      to analysis of variance in univariate and multivariate designs; these data are
      also applied to discriminant function analyses. Species and sex effects on
      morphology are statistically significant; however, no significant interaction of
      these factors is indicated. This would seem to imply that patterns of sexual
      dimorphism are not distinct among great apes; to the contrary, within-species sex
      comparisons reveal that significant size and shape dimorphism is present only in
      Gorilla. Despite significant size dimorphism in Pan and Pongo, significant shape
      differences between males and females are not apparent in these taxa. These
      results suggest that it is theoretically possible to sort taxa by a symphyseal
      shape criterion, but the discriminant function results suggest that there still
      exists a large potential for error in assigning particular shapes to a given
      species or sex. Thus, despite real shape differences among these species, the use
      of symphyseal shape as a character in species identification or in systematic
      arguments remains limited and problematic.

PMID- 10896814
TI  - Taking a new job--the leadership transition.

PMID- 10896815
TI  - Videoscopic Heller myotomy for achalasia--results beyond short-term follow-up.
AB  - BACKGROUND: Heller myotomy has long been utilized for patients failing
      nonoperative management of achalasia. Videoscopy has been advocated to decrease
      the morbidity of Heller myotomy; however, few reports document outcome beyond 1
      year after videoscopic Heller myotomy. PURPOSE: To determine perioperative
      morbidity, relief of dysphagia, and the incidence of postoperative reflux
      symptoms following videoscopic Heller myotomy with follow-up to over 4 years.
      METHODS: Patients with achalasia documented by barium esophogram and esophageal
      manometry underwent videoscopic Heller myotomy beginning in 1992. Intraoperative
      peroral endoscopy was utilized to guide the cephalad and caudad extent of
      myotomy. A barium esophogram was undertaken in the immediate postoperative period
      to evaluate for subclinical leak and assess esophageal emptying. RESULTS: Seventy
      eight patients underwent videoscopic Heller myotomy. The mean age was 51 years +/
      19 (range 14 to 91). Most (62%) patients had undergone pneumatic dilation prior
      to surgical consultation and 54% had previous botox injections. All patients
      complained of dysphagia and 40% had symptoms of heartburn prior to myotomy. After
      myotomy, 91% of patients stated that their swallowing was improved with myotomy.
      Thirteen patients (18%) experience heartburn more than once per week after
      myotomy. The average length of stay was 2 +/- 2 days, with 72% of patients
      spending 2 days or fewer in the hospital. Six (7.7%) major complications
      occurred: five esophageal perforations and one enterotomy without long-term
      sequellae. Three procedures (3.8%) were converted to "open" procedures. No deaths
      occurred. We conclude that videoscopic Heller myotomy is safe and efficacious,
      with low morbidity and mortality. Videoscopic myotomy provides relief beyond the
      short term for dysphagia due to achalasia with minimal reflux symptoms. We
      advocate videoscopic Heller myotomy in the treatment of severe dysphagia due to
      achalasia not adequately palliated by or amenable to nonoperative management.

PMID- 10896816
TI  - Pulmonary vascular pressures increase after lung volume reduction surgery in
      rabbits with more severe emphysema.
AB  - BACKGROUND: Emphysema is a chronic disease of the lungs with destruction of
      terminal alveoli and airway obstruction. Lung volume reduction surgery (LVRS) is
      being investigated for the treatment of emphysema. Increasing resection volumes
      with LVRS may lead to worsening of carbon monoxide diffusing capacity (Dlco)
      despite improvement in compliance and flow. We hypothesized that the pulmonary
      circulation-related parameters, pulmonary artery pressure (PAP) and diffusing
      capacity (Dlco), may be used as indicators of the maximally tolerated LVRS
      resection volume. METHODS: Emphysema was induced in 55 rabbits by endotracheal
      nebulization, with either single 15,000-unit (mild emphysema) or three 11,000
      unit (moderate emphysema) doses of elastase. At Week 6, bilateral LVRS was
      performed via median sternotomy with an endoscopic stapler. Single-breath Dlco,
      static compliance, and PAP were measured prior to emphysema induction,
      preoperatively, and 1 week following LVRS. Animals were divided into the
      following groups: Group I (mild emphysema, <3 g resected), group II (mild
      emphysema, >3 g resected), group III (moderate emphysema, <3 g resected), group
      IV (moderate emphysema, >3 g resected). RESULTS: All animals having LVRS had
      immediate postoperative increase in pulmonary vascular resistance (PVR) following
      lung resection. Mean PAP, however, remained elevated when measured 1 week after
      LVRS (sacrifice) in animals with moderate emphysema. This is in contrast to
      animals with mild emphysema, in which follow-up PAPs approached preoperative
      baseline. CONCLUSION: These finding suggests that sustained increased PVR,
      denoted by elevated PAP, is more likely to occur after LVRS in animals with more
      severe emphysema and larger volume resection. The spirometric and compliance
      benefits of greater resection volumes have to be weighed against the compromise
      in pulmonary vasculature in the effort to determine the ideal resection volume
      for various degrees of emphysema.

PMID- 10896817
TI  - Increased carboplatin concentration in liver tumors through temporary flow
      retardation with starch microspheres (Spherex) and gelatin powder (Gelfoam): an
      experimental study in liver tumor-bearing rabbits.
AB  - Regional chemotherapy of primary and secondary malignant liver tumors is superior
      to systemic therapy. The regional advantage can be further increased by flow
      retardation. Absorbable gelatin powder (Gelfoam) and starch microspheres
      (Spherex) may serve as embolizing agents because of their particle size and
      embolization time. Carboplatin was for the first time applied as a cytostatic
      agent in regional chemotherapy. Embolization and flow retardation times were
      measured. The embolization time of Gelfoam was 27 min, and that of starch
      microspheres (Spherex), 7 min, on average. Mean flow retardation of Gelfoam was
      153 min, and that of starch microspheres (Spherex) 38 min. The concentration
      differences in systemic and regional chemotherapy were determined in VX-2 liver
      tumor-bearing rabbits. In regional chemotherapy, the tumor concentration was
      increased by a factor of 3.6 compared with systemic therapy. Coapplication with
      an embolizing agent increased the tumor concentration of carboplatin by a factor
      of 44 to 47. Concentrations of absorbable gelatin powder (Gelfoam) and starch
      microspheres (Spherex) did not differ significantly.

PMID- 10896818
TI  - The use of insulin and glucose during resuscitation from hemorrhagic shock
      increases hepatic ATP.
AB  - BACKGROUND: Hemorrhagic shock produces a marked decrease in hepatic ATP,
      adenylate energy charge, and total adenosine nucleotides. This is followed by
      slow recovery to normal levels after resuscitation. Nucleotide metabolites are
      increased following shock and resuscitation. Previous experimental work has shown
      that supraphysiologic doses of insulin have salutary effects in animals with
      hemorrhagic shock and in cardiac patients. It appears that insulin causes
      increased availability of glucose and energy-producing substrates. This study
      examined whether resuscitation with glucose and insulin after hemorrhagic shock
      would alter the changes previously seen to occur in hepatic ATP levels, adenylate
      energy charge, or nucleotide metabolites. METHODS: Male Sprague-Dawley rats were
      bled to a mean arterial blood pressure of 40 mm Hg for 30 min. They were then
      resuscitated with the shed blood and one of three fluids: (1) lactated Ringer's,
      (2) lactated Ringer's with 10% glucose, (3) lactated Ringer's with 10% glucose +
      6 units/kg regular insulin. Liver biopsies were obtained prior to shock
      (baseline), after 30 min of shock (shock), and 90 min after resuscitation (90
      min). Tissue levels of ATP, ADP, AMP, adenosine, inosine, hypoxanthine, and
      xanthine were measured. Serum at 90 min was evaluated for potassium, glucose, and
      tumor necrosis factor alpha (TNF-alpha). RESULTS: The insulin-treated group had
      significantly increased hepatic ATP and energy charge following resuscitation
      compared with the other two groups. The insulin group also exhibited significant
      hypoglycemia. Total adenine nucleotides (ATP, ADP, and AMP) were significantly
      elevated 90 min postresuscitation in the insulin group. Mean blood pressures
      throughout the experiment were not significantly different among groups. TNF
      alpha was highest in the insulin-treated group, but this was not significant.
      CONCLUSIONS: Resuscitation with insulin and dextrose significantly increased
      hepatic ATP and adenylate energy charge after hemorrhagic shock in rats. Total
      nucleotide pool levels were not different between groups, indicating that there
      was a shift of the equilibrium away from the metabolites toward ATP and ADP in
      the insulin-treated group. Insulin treatment had no significant effect on blood
      pressure or TNF-alpha. However, it caused significant hypoglycemia and
      hypokalemia.

PMID- 10896819
TI  - Wound healing: captopril, an angiogenesis inhibitor, and Staphylococcus aureus
      peptidoglycan.
AB  - BACKGROUND: Captopril, an angiotensin-converting enzyme inhibitor, used for
      treating hypertension and heart failure, inhibits angiogenesis in the corneas of
      rats in response to basic fibroblast growth factor, slows the growth of
      experimental tumors in rats, and leads to the regression of Kaposi's sarcoma.
      Because angiogenesis is key to wound healing, we hypothesized that captopril
      would impair wound healing. We hypothesized also that because local application
      at operation of Staphylococcus aureus peptidoglycan (SaPG) increases angiogenesis
      and accelerates wound healing in rats, SaPG would prevent or ameliorate the
      postulated captopril-impaired wound healing. MATERIALS AND METHODS: In each
      experiment, rats were divided randomly into two groups: one drinking tap water,
      and the other, tap water containing 0.5 mg captopril/ml. All ate chow and drank
      ad libitum, pre-operatively (4-12 days) and postoperatively (7 days). In
      experiments 1 and 2, bilateral paravertebral 5.5-cm skin incisions were made
      aseptically (intraperitoneal sodium pentobarbital), and closed with interrupted
      No. 35 stainless-steel sutures. On one side, the wound was immediately inoculated
      with 157 microliter pyrogen-free isotonic saline and on the other side the wound
      was inoculated with 157 microliter saline containing 4.7 mg SaPG (860 microgram
      SaPG/cm incision). In the third experiment, polyvinyl alcohol (PVA) sponges (16
      17 mg dry wt each) containing either 50 microliter saline or 0.5 mg SaPG in 50
      microliter saline were implanted subcutaneously, two on each side, via 1-cm
      incisions closed with a single suture. In the fourth experiment, 5.5-cm bilateral
      skin incisions and subcutaneous implantation of PVA sponges were done as
      described but all sites were instilled with saline only. All rats were euthanized
      (CO(2) asphyxia) 7 days postoperatively. RESULTS: Wound breaking strength (WBS)
      of the saline-treated incisions was significantly higher (P < 0.001) in captopril
      treated rats than in controls (172 +/- 13 g vs 105 +/- 6 g) in experiment 1 and
      higher, but not significantly in captopril-treated rats in experiment 2 (153 +/-
      8 g vs 114 +/- 6 g) (PNS). SaPG inoculation of the incisions increased WBS
      significantly in both control and captopril-treated rats: 187 +/- 11 g vs 105 +/-
      6 g (P < 0.001) and 283 +/- 16 g vs 172 +/- 13 g (P < 0.001), respectively, in
      experiment 1, and 217 +/- 13 g vs 114 +/- 6 g (P < 0.0001) (controls) and 266 +/-
      17 g vs 153 +/- 8 g (captopril-treated rats) (P < 0.0001) in experiment 2. In
      experiment 3, subcutaneous PVA saline-inoculated sponge reparative tissue
      hydroxyproline (OHP) content was similar in control and captopril-treated rats,
      and SaPG inoculation increased reparative tissue OHP significantly in both
      groups: 2458 +/- 218 microgram/100 mg dry sponge vs 3869 +/- 230 microgram/100 mg
      (P < 0.001) (controls) and 2489 +/- 166 microgram/100 mg vs 4176 +/- 418
      microgram/100 mg (P < 0.001) (captopril-treated rats). Histologically,
      angiogenesis and reparative tissue collagen were similar in control and captopril
      treated rats, in both saline-inoculated and SaPG-inoculated sponges. In
      experiment 4 (all incisions and subcutaneous PVA sponges were saline-inoculated),
      there was no significant difference in WBS between control and captopril-treated
      rats (107 +/- 6 g vs 96 +/- 5 g, NS). PVA sponge reparative tissue OHP was
      significantly higher in captopril-treated rats: 3698 +/- 170 microgram/100 mg dry
      sponge vs 2534 +/- 100 microgram/100 mg (P < 0.0001). CONCLUSION: Unexpectedly,
      in four experiments, captopril did not inhibit WBS or PVA sponge reparative
      tissue angiogenesis or collagen accumulation; in fact, WBS was increased
      significantly in one of three experiments, and PVA sponge reparative tissue OHP
      was increased significantly in one of two experiments. Also, captopril did not
      interfere with the wound healing-accelerating effect of SaPG.

PMID- 10896820
TI  - Detrimental effects of octreotide on intestinal microcirculation.
AB  - BACKGROUND: Octreotide (OCT) is used for the protection of pancreato-intestinal
      anastomoses and for treatment of acute pancreatitis. Its effect on jejunal
      microcirculation after ischemia-reperfusion has not been investigated. MATERIAL
      AND METHODS: Intestinal ischemia was induced in Wistar rats (n = 8) by occlusion
      of the superior mesenteric artery for 40 min. Prior to reperfusion infusion of
      OCT (7.5 microgram/h) was started (n = 8). Microvascular perfusion of the jejunal
      mucosal and muscle layers was assessed and compared with that of groups without
      intervention (n = 16) by means of intravital microscopy. RESULTS: Ischemia
      reperfusion decreased mucosal functional capillary density from 838.4 +/- 12.6 to
      418.9 +/- 9.6 cm(-1). Mucosal capillary red blood cell velocity was reduced from
      0.53 +/- 0.01 to 0.35 +/- 0.01 mm/s (P < 0.05). Permanent leukocyte adherence was
      increased. OCT without ischemia-reperfusion decreased functional capillary
      density (735.4 +/- 13.5 cm(-1)) and red blood cell velocity (0.46 +/- 0.01 mm/s).
      After reperfusion OCT led to perfusion heterogeneity demonstrated by villous
      stasis (26 +/- 4%) and a decrease in the index of mucosal perfusion (0.38 +/-
      0.02). Functional capillary density was further decreased compared with ischemic
      controls (234.0 +/- 11.8 cm(-1)). Capillary red blood cell velocity was lower
      (0.30 +/- 0.01 mm/s) than in ischemic controls. CONCLUSIONS: OCT impairs
      microvascular perfusion of the jejunum both under physiological conditions and
      after ischemia-reperfusion.

PMID- 10896821
TI  - Renal amino acid metabolism during endotoxemia in the rat.
AB  - BACKGROUND: The kidney has an important function in the exchange of nitrogenous
      metabolites. Glutamine is the most important substrate for renal ammoniagenesis
      and thus plays a crucial role in acid-base homeostasis. Furthermore, the kidney
      is the main endogenous source for de novo arginine production from citrulline,
      which in turn is derived from intestinal glutamine metabolism. Sepsis is a
      condition in which glutamine availability is reduced, whereas the need for
      arginine biosynthesis may be increased. Limited bioavailability of glutamine may
      affect arginine synthesis, which may have consequences for nitric oxide (NO)
      synthesis. Therefore, we studied renal glutamine and arginine metabolism in a rat
      model of endotoxemia and related this to NO metabolism. MATERIALS AND METHODS:
      Rats were subject to double hit endotoxemia, and control rats received 0.9% NaCl.
      Renal blood flow was measured using para-aminohippuric acid. Concentrations of
      plasma amino acids and nitrate were measured in the aorta and renal vein to
      calculate net renal uptake or release of amino acids and address NO production.
      RESULTS: The arterial concentrations of glutamine and ammonia were not changed in
      endotoxemic rats. Although renal glutamine uptake was reduced, total renal
      ammonia production was not changed during endotoxemia. The arterial concentration
      of citrulline and renal citrulline uptake was not altered in endotoxin-treated
      rats, but renal arginine production was increased. However, no effect was
      observed on nitric oxide production. CONCLUSIONS: Although the kidney has very
      important functions in the excretion of waste products and in interorgan
      metabolism, this study suggests that the kidney has a limited role in glutamine,
      arginine, and NO metabolism during late endotoxemia in rats.

PMID- 10896822
TI  - omega-3 fatty acids decrease endothelial adhesion of human colorectal carcinoma
      cells.
AB  - BACKGROUND: Diets rich in omega-3 fatty acids have been shown to decrease both
      the initiation and promotion of colon carcinogenesis although their effect on
      hepatic metastasis formation is less well understood. Since adhesion of human
      colorectal carcinoma (HCRC) cells to hepatic endothelial cells is an important
      step in the metastatic cascade, the effect of membrane omega-3 fatty acid
      alterations on endothelial cell adhesion was studied. MATERIALS AND METHODS: CX-1
      cells, a moderately differentiated HCRC cell line known to produce hepatic
      metastases in an athymic mouse intrasplenic injection model, were used. Cells
      were grown in omega-3 fatty acid-enriched medium and membrane-free fatty acid
      modifications confirmed with gas chromatography. Both human umbilical vein and
      hepatic sinusoidal endothelial cells were used in the binding assays. Adhesion
      assays were performed in a standard fashion using (51)Cr-labeled cells to tumor
      necrosis factor (TNF)-stimulated endothelial cell monolayers. Immunohistochemical
      analysis was performed for sialyl-Lewis(x), the receptor involved in endothelial
      adhesion on the surface of control and fatty acid-modified cells. RESULTS: Gas
      chromatographic analysis confirmed membrane fatty acid modification of CX-1 cells
      by growth in docosahexanoic acid (omega-3) (4.761 nmol/10(6) cells vs 0.057
      nmol/10(6) cells for controls). Binding of CX-1 to both human umbilical vein and
      hepatic sinusoidal endothelial cells decreased from 38.4 +/- 0.44 to 11.58 +/-
      0.87% (P < 0.01). Immunocytochemical analysis showed a decrease in sialyl
      Lewis(x) expression with omega-3 treatment. CONCLUSIONS: These data indicate that
      omega-3 fatty acids may also be protective against the formation of hepatic
      metastases. The mechanism for this may be decreased endothelial cell adhesion
      which in turn may be due to decreased expression of the endothelial receptor
      sialyl-Lewis(x).

PMID- 10896823
TI  - Hemorrhage and resuscitation induce delayed inflammation and pulmonary
      dysfunction in mice.
AB  - BACKGROUND: It is well known that hemorrhagic shock induces inflammatory changes.
      Our objective was to study the histologic and biochemical changes in the lung and
      evaluate alterations in respiratory function after hemorrhage and resuscitation
      (H/R) in mice. METHODS: After 30 min of hemorrhagic shock, mice were resuscitated
      with shed blood to restore mean arterial blood pressure to baseline. A sham group
      was anesthetized and instrumented for 30 min, but did not undergo hemorrhage.
      Myeloperoxidase (MPO) levels were measured and histologic analysis was performed
      on lung tissue. Pulmonary function was evaluated using whole-body plethysmography
      (WBP) 1, 3, and 5 days postprocedure. Alveolar function was evaluated by
      measuring carbon monoxide uptake via gas chromatography 5 days after H/R.
      RESULTS: Five days after H/R, mice exposed to shock had significantly higher lung
      MPO levels and showed greater histologic evidence of lung injury. Airway
      resistance (Penh) in the sham mice was 0.91 +/- 0.06 versus 1.21 +/- 0.09 in the
      hemorrhage group (P < 0.01). Alveolar function was significantly decreased in the
      H/R group (70.8 +/- 3.6%) compared with shams (81.6 +/- 1.8%) (P < 0.05).
      CONCLUSIONS: Hemorrhage and resuscitation cause delayed biochemical, histologic,
      and physiologic changes in the lung. These were marked by increased lung MPO,
      increased neutrophils, and decreased alveolar function. The alterations of
      pulmonary function and structure were most severe 5 days after H/R.

PMID- 10896824
TI  - Cd1d-restricted cellular lysis by peripheral blood lymphocytes: relevance to the
      inflammatory bowel diseases.
AB  - The CD1d molecule has been implicated to play a role in inflammatory bowel
      diseases (IBD), possibly through its presentation of an intestinal antigen
      trigger. To understand the role of the CD1d class I-like protein in IBD, we
      investigated the molecule's expression in diseased intestinal tissue and
      determined its potential to undergo specific recognition by intraepithelial and
      peripheral blood lymphocytes (PBLs) derived from IBD patients. We have observed
      an increase in precipitable CD1d in inflamed tissues, which suggests CD1d up
      regulation in IBD; this was not accompanied by the occurrence of CD1d-specific
      cytotoxicity by lymphocytes isolated from the same tissue sites. In contrast, we
      have observed CD1d-specific cytotoxicity by PBLs from both patients and normal
      controls mediated by a possibly unique type of lymphocytic cell. These
      observations support a model in which intestinal inflammation may be initiated by
      circulating PBLs following the tissue-specific upregulation of CD1d. These
      activated PBLs may then be the source of the extraintestinal manifestations
      observed with IBD. We therefore propose that the cells responsible for this
      activity may play a role in regulating immune responses through the specific
      recognition of CD1d-specific antigen(s).

PMID- 10896825
TI  - Hepatic parenchymal cell volume and the indocyanine green tolerance test.
AB  - BACKGROUND: Precise evaluation of the hepatic function of preoperative patients
      with liver cirrhosis is controversial. Hepatic functional capacity cannot be
      evaluated easily because hepatic function is not based on morphological aspects.
      PURPOSE: The aim of this study was to evaluate hepatic function with a new
      procedure of the indocyanine green (ICG) tolerance test using an ICG clearance
      meter, and to compare liver parenchymal cell volume with hepatic function.
      PATIENTS AND METHODS: Sixteen patients (seven with histologically normal liver
      and nine with histologically proven liver cirrhosis) scheduled for liver
      resection were selected randomly for the study. Measurement of two blood
      disappearance rate constants of ICG, k(100-900) and k(100-300), and effective
      hepatic blood flow (EHBF) using an ICG clearance meter, as well as conventional
      ICG-k(5,10,15) and ICG-R15, was performed. We calculated k(100-300) and EHBF
      using the early disappearance rate of ICG with the ICG clearance meter. Liver
      parenchymal cell volume was measured using CT volume and the liver parenchymal
      cell ratio with computer-aided image analysis. RESULTS: The value of ICG-k(100
      300) was mostly proportional to liver parenchymal cell volume. EHBF per liver
      parenchymal cell volume did not differ between normal and cirrhotic subjects.
      CONCLUSIONS: ICG-k(100-300) and EHBF are good indices of liver function and are
      proportional to liver parenchymal cell volume. Hepatic dysfunction in cirrhosis
      is due to a decrease in liver parenchymal cell volume.

PMID- 10896826
TI  - Cutaneous window for in vivo observations of organs and angiogenesis.
AB  - BACKGROUND AND OBJECTIVE: The continuous observation in experimental animals of
      internal organs and processes, such as wound healing and angiogenesis, has been
      achieved using a variety of transparent windows and chambers. Our objective was
      to develop procedures for these observations using disposable material for the
      window and simple surgical techniques. METHODS: For observation of wound healing
      in the mouse kidney, the kidney was externalized and a wedge was excised. An oval
      window of polyvinyl chloride film was sutured in place in the skin over the
      wound. The progress of healing of the wound was observed through the window over
      10 days. For observation of angiogenesis, adrenocortical cells were transplanted
      beneath fascia and muscle and a window was sewn into the skin above the site of
      transplantation. RESULTS: Clear observations could be made using these cutaneous
      windows over the period of the experiments. Healing of a wound in the kidney was
      photographed and measured. The growth of new blood vessels over the site of
      adrenocortical cell transplantation was observed. CONCLUSIONS: Continuous in vivo
      observations of organs such as the kidney and processes such as angiogenesis can
      be made in experimental animals using this simple technique.

PMID- 10896827
TI  - Nicotine reorganizes cytoskeleton of vascular endothelial cell through platelet
      derived growth factor BB.
AB  - BACKGROUND: Cigarette smoking has been directly linked to atherosclerosis
      formation and vascular graft failures but the role of nicotine in these processes
      is not yet completely understood. We investigated the release of platelet-derived
      growth factor BB (PDGF BB) by the bovine aortic endothelial cell (EC) after
      nicotine administration at concentrations similar to those found in plasma of
      active and passive smokers and the role of PDGF BB, autocrinally released, in EC
      cytoskeletal modification. METHODS: EC were stimulated in a serum-free medium for
      72 h with (-)-nicotine (from 6 x 10(-4) to 6 x 10(-8) M). The release of PDGF BB
      was assessed by inhibition antibody-binding assay and confirmed by Western
      blotting. Mitogenic activity of nicotine on EC was also determined. The EC
      cytoskeleton was studied with specific antibodies anti-alpha-actin fibers and
      anti-vimentin and the modification induced by PDGF BB was assessed by blocking
      PDGF BB activity with specific antibodies. RESULTS: The greatest PDGF BB release
      was noted at a (-)-nicotine concentration of 6 x 10(-6) M (P < 0.001). The
      addition of antibody anti-PDGF BB to EC exposed to (-)-nicotine decreased
      tritiated thymidine uptake by 20% (P < 0.001). EC exposed to (-)-nicotine
      concentrations of 6 x 10(-6) and 6 x 10(-8) M had a significant alteration in the
      expression of alpha-actin fibers and vimentin as compared with control.
      Administration of the antibody anti-PDGF BB in the culture medium reversed
      cytoskeletal alteration. CONCLUSIONS: Nicotine enhanced the release of PDGF BB by
      EC which in turn caused an alteration in cytoskeletal organization.

PMID- 10896828
TI  - Identification of high-risk residents.
AB  - BACKGROUND: Identification of high-risk residents allows remediation and support
      for administrative action when necessary. This study characterizes differences in
      documentation of marginally performing residents in a general surgery residency.
      METHODS: High-risk residents were identified by the former program director.
      Twenty-four of one hundred fifteen residents over a 10-year period had one to
      four problematic areas: cognitive, synthetic, family/health, and interpersonal
      skills. Outcomes included finished (18), voluntary withdrawal (1), and
      involuntary withdrawal (5). A case-control study matching controls to cases by
      date of entry into the training program was used. Records were reviewed for
      demographics, preentry qualifications, American Board of Surgery In-Training Exam
      (ABSITE) scores, letters of complaint or praise, events of counseling, and
      monthly ratings. The records of 48 residents were reviewed. Ward evaluations were
      on eight categories with a 5-point Leikert scale (3-unacceptable to 7
      outstanding). The evaluation score assigns points only to low ratings. High
      scores represent progressively poorer performance. A Wilcoxon signed ranks test
      was used to compare the cases and controls for continuous variables. The McNemar
      test was used in comparisons of categorical data with binary outcomes. Exact P
      values are reported. RESULTS: Objective data were similar for both groups. Study
      residents tended to score higher on monthly evaluations at Year 2 and by Year 3
      this achieved significance (0.026). Study residents were more likely to have
      negative faculty letters (0.016) and events of counseling by a faculty member
      (0.017) and the program director (0.005). CONCLUSIONS: Identification of
      residents at risk should begin as early as possible during training. A
      combination of faculty evaluations and evidence of letters of counseling can
      detect high-risk residents. Programs may use such indicators to support decisions
      regarding remedial work or administrative action.

PMID- 10896829
TI  - Patterning of the "distal esophagus" in esophageal atresia with tracheo
      esophageal fistula: is thyroid transcription factor 1 a player?
AB  - BACKGROUND: We have recently proposed that the "distal esophagus" in esophageal
      atresia with tracheo-esophageal fistula (EA/TEF) is actually embryologically
      derived from the middle branch of a trifurcation of the embryonic lung bud, which
      subsequently grows caudally in the foregut to connect with the developing
      stomach. We hypothesized that differential mRNA expression of the lung-specific
      patterning transcription factor, thyroid transcription factor 1 (TTF-1), in the
      developing fistula tract in TEF relative to the bronchi (the other branches of
      the lung bud trifurcation) might explain the unique nonbranching pattern of
      growth of the fistula tract. MATERIALS AND METHODS: EA/TEF was induced in Sprague
      Dawley rat embryos via intraperitoneal injection of 2.2 mg/kg adriamycin into
      pregnant dams on Days 6-9 of gestation. The foregut from embryos developing
      EA/TEF and from control embryos (no adriamycin) were isolated on Gestational Days
      13.5, 15.5, and 17.5 (term = 21 days). Some were processed for whole-mount in
      situ hybridization for TTF-1, while others were embedded and sectioned for
      histologic analysis via in situ hybridization for TTF-1. RESULTS: The expression
      of the respiratory-specific transcription factor TTF-1 is conserved in the
      epithelium of the developing fistula tract in TEF. The pattern of expression of
      TTF-1 in the fistula tract mirrors the expression in the large airways of the
      developing lungs, despite the fact that the fistula tract does not form secondary
      branches to give rise to a lung. CONCLUSIONS: The fistula tract in TEF is a
      respiratory-derived structure that expresses the lung-specific transcription
      factor TTF-1 throughout its development in the foregut. Contrary to the
      patterning role that it normally plays in the developing lung, TTF-1 does not
      induce branching morphogenesis in the fistula tract. Thus, the nonbranching
      pattern of growth of the fistula tract may be attributable to local mesenchymal
      epithelial interactions that override TTF-1 patterning activity.

PMID- 10896830
TI  - Tissue oxygen pressure during prolonged ischemia of the liver.
AB  - BACKGROUND: The potential role of hepatovenous back-perfusion in maintaining
      organ viability of the inflow-occluded liver has been reported with respect to
      aspects of tissue perfusion and energy metabolism. In the present study, the
      physiological differences between liver ischemia induced by portal triad clamping
      (PTC) and that induced by total hepatic vascular exclusion (THVE) were
      investigated in a porcine disease model, with special reference to changes in
      tissue oxygen pressure (PtO(2)) of the liver. MATERIALS AND METHODS: Twelve
      female pigs were used for induction of 60 min of normothermic liver ischemia.
      They were assigned to two groups: a PTC group (n = 6) and a THVE group (n = 6).
      PtO(2) was measured before, during, and after the ischemic period at two
      different points in the middle lobe: on the central side close to the
      hepatovenous confluence and on the peripheral side close to the gallbladder bed.
      RESULTS: Although central PtO(2) decreased during ischemia in both groups, PTC
      group values at 40 and 60 min of ischemia remained significantly higher than THVE
      group values (60 +/- 28 and 42 +/- 21 mmHg vs 11 +/- 5 and 13 +/- 3 mmHg,
      respectively; means +/- SD). Peripheral PtO(2) in the PTC group during ischemia
      was low in comparison to corresponding central PtO(2) values. CONCLUSION: Oxygen
      supply to the tissue via hepatovenous reflux may contribute to maintaining organ
      viability under prolonged inflow occlusion of the liver.

PMID- 10896831
TI  - The cysteine-free fibroblast growth factor 1 mutant induces heparin-independent
      proliferation of endothelial cells and smooth muscle cells.
AB  - BACKGROUND: The structure/function relationships of fibroblast growth factor 1
      (FGF-1) are being investigated using site mutation, yielding novel structures
      with potential clinical applicability for modulating tissue responses to vascular
      interventions. We generated a mutant FGF-1 in which all three cysteines were
      converted to serines and then tested the relative mitogenic activities on
      endothelial cells (ECs) and smooth muscle cells (SMCs) and the molecular
      stability of the protein to thrombin-induced degradation. METHODS: The dose
      responses of wild-type FGF-1 and the Cys-free mutant in the absence or presence
      of heparin were tested on ECs and SMCs. Cell proliferation was measured by
      [(3)H]thymidine incorporation. Data were normalized by positive control (20%
      fetal bovine serum) and expressed as percentage of positive control for
      comparison. The molecular stability was examined by exposure of the cytokines to
      thrombin at 37 degrees C for 0.5-24 h and then analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. RESULTS: Unlike wild-type FGF-1 which induced
      only minimal DNA synthesis at concentrations as high as 100 ng/ml, the Cys-free
      mutant induced a dose-dependent proliferation starting at 1 ng/ml on both ECs and
      SMCs in the absence of heparin. At 100 ng/ml, Cys-free mutant induced 4-fold more
      proliferation than wild-type FGF-1 on ECs (76.64 +/- 13.39% vs 14.58 +/- 1.38%, P
      < 0.01) and 12-fold more proliferation on SMCs (143.52 +/- 9.96 vs 11.25 +/-
      3.32, P < 0.01). Heparin 5 U/ml potentiated the mitogenic activity of the Cys
      free mutant at low dose range. Both proteins were degraded by thrombin
      progressively. But the Cys-free mutant showed more susceptibility with
      accelerated appearance of lower-molecular-weight fragment bands after incubation
      with thrombin. CONCLUSIONS: Conversion of cysteine residues to serine changed the
      heparin dependency of the growth factor and increased its mitogenic activity and
      its susceptibility to thrombin-induced degradation.

PMID- 10896832
TI  - Recombinant human hepatocyte growth factor protects the liver against hepatic
      ischemia and reperfusion injury in rats.
AB  - BACKGROUND: Recent evidence indicates that hepatocyte growth factor (HGF) has a
      cytoprotective effect against hepatic injury caused by hepatotoxins and
      inflammatory cytokines. Studies were performed to determine whether HGF
      influences the survival rate of rats subjected to hepatic warm
      ischemia/reperfusion (WI/Rp) injury. METHODS: Male Sprague-Dawley rats were
      subjected to total or segmental hepatic ischemia by occluding the hepatic artery,
      portal vein, and bile duct with a microvascular clip. Rats were treated with four
      intravenous injections of recombinant human HGF (rhHGF 1 mg/kg) or the vehicle
      72, 48, 24, and 12 h before surgery. RESULTS: None of the eight animals in the
      control group were alive 12 h after total hepatic WI/Rp. Seven of eight animals
      in the rhHGF-treated group were alive more than 2 days after the reperfusion. In
      the model of segmental hepatic ischemia, rhHGF inhibited the increase in cytokine
      induced neutrophil chemoattractant in serum. The number of neutrophils
      infiltrating the liver was significantly lower in the rhHGF-treated group than in
      the control group. rhHGF prevented increases in the activity of serum alanine
      transaminase and in hepatic necrosis. Experiments with proliferating cell nuclear
      antigen staining demonstrated that hepatocyte proliferation markedly increased in
      rhHGF-treated rats as compared with controls. CONCLUSIONS: These results indicate
      that HGF facilitates recovery of the liver from hepatic WI/Rp injury, at least in
      part through the prevention of neutrophil infiltration and the activation of
      hepatocyte proliferation.

PMID- 10896833
TI  - The high level of hCDC10 gene expression in neuroblastoma may be associated with
      favorable characteristics of the tumor.
AB  - BACKGROUND: The biological behavior of neuroblastomas detected through mass
      screening (MS, </=1 year of age) and that of mass screening-negative later
      presenting (MSN, >1 year of age) neuroblastomas have been reported to differ in
      many studies. To investigate the biological differences between these two groups,
      we analyzed the differences in mRNA profiles. MATERIALS AND METHODS: We analyzed
      the mRNA profiles of MS and MSN neuroblastomas using differential display, and
      cloned and sequenced the bands differentially expressed between these two groups.
      Using the RNA analysis by polymerase chain reaction (RNA-PCR) method, the
      relative amount of mRNA in tumor tissue in each sample was measured. Associations
      between relative amount of mRNA and clinical and genetic variables related to
      patient prognosis and the effect of the level of mRNA expression on survival
      probability were investigated using statistical methods. RESULTS: Using
      differential display and RNA-PCR, we found that the mRNA for the human homologue
      of the yeast cdc10 gene (hCDC10) identified in Saccharomyces cerevisiae was
      expressed at a higher level in the MS group of patients than in the MSN group of
      patients (0.554 +/- 0.197 for MS neuroblastoma, n = 24 and 0.244 +/- 0.179 for
      MSN neuroblastoma, n = 10, P < 0.01), and this difference was suggested to be
      independent of the histologic subtype of tumor. A high level of hCDC10 mRNA
      expression in neuroblastomas (relative amount of hCDC10 mRNA > 0.35) was also
      suggested to be associated with younger age at diagnosis (</=1 year of age, P <
      0.01), favorable clinical stage (I, II, and IVs, P < 0. 01), and favorable
      histology in the Shimada classification (P < 0. 01), whereas a low level of
      hCDC10 mRNA expression (relative amount of hCDC10 mRNA </=0.35) was suggested to
      be associated with the progression of clinical stage (P < 0.01) and N-myc gene
      amplification (>1 copy, P < 0.05). Patients with neuroblastomas with a high level
      of hCDC10 mRNA expression were suggested to have a better prognosis than those
      with a low level of hCDC10 mRNA expression (P < 0.01). CONCLUSIONS: A high level
      of hCDC10 mRNA expression in neuroblastomas may be associated with favorable
      clinical and biological characteristics, and the expression of hCDC10 mRNA in
      neuroblastomas may affect the clinical and biological characteristics of this
      type of tumor.

PMID- 10896834
TI  - Impaired Kupffer cell function and effect of immunotherapy in obstructive
      jaundice.
AB  - BACKGROUND: Obstructive jaundice is frequently associated with septic
      complications. This study examined the influence of biliary obstruction on
      bacterial clearance and translocation. The study focused on the phagocytic and
      killing activities of Kupffer cells and the preventive effect on bacterial
      translocation of OK-432, which is a hemolytic streptococcal preparation developed
      as a biological response modifier. METHODS: To study the mechanism of sepsis in
      obstructive jaundice, two groups of Wistar rats were examined: rats subjected to
      common bile duct ligation (CBDL) and rats subjected to a sham operation.
      Bacterial clearance, organ distribution, hepatic blood flow, and phagocytic
      function of Kupffer cells were examined. To evaluate the effect of OK-432 on
      bacterial translocation, rats were divided into three groups: sham operation +
      phosphate-buffered saline (PBS), CBDL + PBS, and CBDL + OK-432. RESULTS: In this
      study, clearance of Escherichia coli. from the peripheral blood in CBDL rats was
      decreased significantly compared with that in sham-operated rats. Significant
      decreases in E.coli trapped in the liver and in hepatic blood flow were observed
      in CBDL rats compared with sham-operated rats. Phagocytic activity and superoxide
      production of Kupffer cells isolated from CBDL rats were significantly lower than
      in sham-operated rats. The incidence of bacterial translocation in CBDL rats was
      increased significantly, and oral administration of OK-432 prevented it.
      CONCLUSION: The results suggest that susceptibility to infection in obstructive
      jaundice is due to impaired phagocytic function of Kupffer cells. Furthermore,
      obstructive jaundice promotes bacterial translocation, and OK-432 may be useful
      in preventing this translocation.

PMID- 10896835
TI  - Protease activation during surgical stress in the rat small intestine.
AB  - BACKGROUND: Surgical stress affects intestinal permeability and our earlier study
      using a rat model indicated that oxidative stress plays an important role in this
      process. Proteases are important mediators of cellular damage and are known to be
      activated in oxidative stress. This study looked at protease activity in
      enterocytes after surgical stress. METHODS: Surgical stress was induced by
      opening the abdominal wall and handling the intestine as done during laparotomy,
      in normal and xanthine oxidase-deficient rats. Enterocytes at various stages of
      differentiation were isolated and protease activity and protection offered by
      xanthine oxidase inhibitors were determined. Mitochondria and cytosol were
      prepared from total isolated enterocytes at different periods after surgical
      stress and protease activation was studied. RESULTS: Surgical stress induced
      activation of proteases in both the villus and crypt cells. Protease activation
      is seen in both mitochondria and cytosol, and similar to the other alterations in
      mucosal cells, protease activation was maximum 60 min after stress, returning to
      normal by 24 h. Thiol compounds modulate protease activity in both mitochondria
      and cytosol and the activation is not seen in xanthine oxidase-deficient animals.
      CONCLUSIONS: Surgical stress induces activation of proteases in villus and crypt
      cells of the small intestine. Both mitochondrial and cytosolic proteases are
      activated and free radicals generated by xanthine oxidase may mediate protease
      activation after surgical stress in the intestine.

PMID- 10896836
TI  - Surgical stress and the gastrointestinal tract.
AB  - Surgery on any part of the body results in a wide spectrum of alterations in
      normal body homeostasis. The gastrointestinal tract is extremely sensitive to
      surgical stress, even at remote locations. It is now evident that the G.I. tract
      also plays an important role in development of postoperative complications, such
      as the systemic immune response syndrome and multiple organ failure syndrome. The
      amount of information available on the cellular and subcellular changes occurring
      in the gastrointestinal tract after surgical stress is scant. These changes are
      important since they would act as initiators of tissue damage seen at a later
      stage, which in turn lead to postoperative complications. This review looks at
      the information available on the effect of surgical stress on the small
      intestine, the role of oxygen free radicals in this process, and the changes
      occurring at the cellular level.

PMID- 10896837
TI  - Risk of type 2 diabetes mellitus in young adults from a biracial community: the
      Bogalusa Heart Study.
AB  - BACKGROUND: Since type 2 diabetes has a strong familial component,
      characteristics of young adult offspring of type 2 diabetics were examined in a
      community sample to determine early abnormalities in black and white persons at
      risk. METHODS: The sample consisted of 1,338 fasting young adults (72% white, 28%
      black) aged 19 to 37 years from a biracial community, including those with
      positive parental history of type 2 diabetes (one offspring per family, n = 230)
      or conditions of impaired fasting glucose and type 2 diabetes (n = 22). RESULTS:
      Positive family history of diabetes or impaired fasting glucose and type 2
      diabetes in young adults of both races were significantly associated with adverse
      profiles of measures of obesity and abdominal fat (body mass index, triceps and
      subscapular skinfolds, waist circumference, and abdominal height), systolic and
      diastolic blood pressures, serum total cholesterol, triglycerides, VLDL
      cholesterol, and HDL cholesterol, and indicators of glucose homeostasis (plasma
      glucose and insulin and insulin resistance index). The magnitude of the
      differences in obesity and abdominal fat measures and plasma glucose between
      individuals with and without parental diabetes was greater among blacks versus
      whites (P = 0. 047-0.004). Further, black offspring of both diabetics and non
      diabetics had unfavorable profiles of obesity and abdominal fat measures, blood
      pressure, insulin, and insulin resistance index (P = 0.0001). In a multivariate
      analysis, adiposity measured as body mass index (P = 0.03) and plasma glucose (P
      = 0.003) emerged as the two independent characteristics that distinguished those
      with parental diabetes from those without parental disease. Insulin (P = 0.0001)
      and the insulin resistance index (P = 0.0001) were independently associated with
      conditions of impaired fasting glucose or type 2 diabetes. CONCLUSIONS: The risk
      factors of young adults with parental type 2 diabetes or conditions of impaired
      fasting glucose and type 2 diabetes can be detected early. These observations
      have implications for early prevention and intervention, especially for blacks.

PMID- 10896838
TI  - Children and sports. A message from Preventive Medicine and your physician.

PMID- 10896839
TI  - Diet diversity and colorectal cancer.
AB  - BACKGROUND: Food diversity has been recommended to achieve a healthy diet and
      prevent cancer. The relation between diet diversity and the risk of colorectal
      cancer was investigated using data from a multicenter case-control study carried
      out between 1992 and 1996 in Italy. METHODS: The study included 1225 subjects
      with cancer of the colon (688 men and 537 women), 728 with cancer of the rectum
      (437 men and 291 women), and 4154 controls (2073 men and 2081 women) residing in
      the same geographical areas. Odds ratios (ORs) of colon and rectal cancer and the
      corresponding 95% confidence intervals (CI) according to food diversity were
      derived from unconditional multiple logistic regression equations. RESULTS: For
      colon cancer, an inverse association for total diversity was found in males
      (adjusted OR of 0.65 for the highest vs the lowest quintile of total diversity;
      95% CI: 0.46-0.93) and in females (OR = 0.85; 95% CI: 0.57-1.26). With respect to
      specific food groups, there was an inverse association only with diversity within
      vegetables (OR = 0.66; 95% CI: 0.54-0.81 in colon cancer and OR = 0.71; 95% CI:
      0.55-0.91 in rectal cancer). CONCLUSIONS: This study suggests that total
      diversity is moderately related to a decreased risk of colorectal cancer risk. A
      better understanding of the potential influence of dietary patterns on colorectal
      cancer is needed.

PMID- 10896840
TI  - Social-cognitive and perceived environment influences associated with physical
      activity in older Australians.
AB  - BACKGROUND: Regular physical activity in older adults can facilitate healthy
      aging, improve functional capacity, and prevent disease. However, factors
      associated with physical inactivity in older populations are poorly understood.
      This study attempts to identify social-cognitive and perceived environmental
      influences associated with physical activity participation in older populations.
      METHODS: In a randomly selected sample of 449 Australian adults age 60 and older,
      we assessed self-reported physical activity and a range of social-cognitive and
      perceived environmental factors. Respondents were classified as sufficiently
      active and inactive based on energy expenditure estimates (kcal/week) derived
      from self-reported physical activity. Two logistic regression models, with and
      without self-efficacy included, were conducted to identify modifiable independent
      predictors of physical activity. RESULTS: Significantly more males than females
      were physically active. Physical activity participation was related to age with a
      greater proportion of those age 65-69 being active than those age 60-64 or 70 or
      older. High self-efficacy, regular participation of friends and family, finding
      footpaths safe for walking, and access to local facilities were significantly
      associated with being active. CONCLUSION: Identifying predictors of physical
      activity in older populations, particularly social support, facility access, and
      neighbourhood safety, can inform the development of policy and intervention
      strategies to promote the health of older people.

PMID- 10896841
TI  - Smoking cessation among African Americans: what we know and do not know about
      interventions and self-quitting.
AB  - BACKGROUND: Many studies on cessation interventions and self-quitting have been
      conducted, but few have focused on African Americans. The purpose of this review
      was to critically evaluate the available studies and make recommendations for
      future research. METHODS: Articles published from 1988 to 1998 were collected
      using Medline and other data bases, as well as personal communication. Studies
      were divided into two categories: evaluations of specific cessation interventions
      and examinations of self-quit behaviors and related factors. Studies were
      tabulated using author/year, study design/sample size, variables/results, and
      comments. RESULTS: In the intervention studies, church-based programs may provide
      an effective location for cessation interventions, but the studies to date did
      not demonstrate unequivocal effectiveness. In clinic programs, there do not
      appear to be any interventions that are particularly effective. In community
      based interventions, there were no differences for African and Caucasian
      Americans. With regard to self-quitting, sociodemographic variables were
      similarly related to cessation as in the general population, as were smoking
      history variables. All other categories did not contain enough information for
      firm conclusions to be drawn. CONCLUSIONS: There are some interventions that
      appear to be useful, but little information is available on self-quitting. More
      research is needed on the natural history of quitting, on the social norms for
      smoking among African American groups, and on the conceptual dimensions of race
      in the context of this research.

PMID- 10896842
TI  - The relative importance of social versus commercial sources in youth access to
      tobacco, alcohol, and other drugs.
AB  - BACKGROUND: Youth substance use began to increase in 1992 following a decade-long
      decline, leading to increased interest in controlling access to tobacco, alcohol,
      and other drugs. METHODS: The anonymous and voluntary Minnesota Student Survey
      was administered to 133,794 public school students in grades 6, 9, and 12.
      Questions addressed current frequency of use of tobacco, alcohol, and other drugs
      and how students obtained these substances. Data were analyzed to determine the
      relationship between grade level, gender, race/ethnicity, use frequency, and
      access to substances through social and commercial sources. (Tobacco analyses
      were limited to students under age 18 years.) RESULTS: Social sources (especially
      friends) predominate across all age groups and substances. Students are much more
      likely to obtain tobacco than alcohol from commercial sources but few rely
      exclusively on commercial sources for either. Females and infrequent users are
      more likely to depend on social sources exclusively while males and frequent
      users are more likely to use commercial sources. CONCLUSIONS: Because substances
      are easily accessible through social sources, prevention policies directed at
      retail outlets may not have the desired effect on reducing teen smoking and
      drinking. Greater attention to reducing access to all substances from social
      sources is needed.

PMID- 10896843
TI  - Mothers as active partners in the prevention of childhood diseases: maternal
      factors related to immunization status of preschool children in Italy.
AB  - BACKGROUND: We examined how maternal socio-demographic factors, together with
      mother's education, knowledge, and perception of immunizations, can affect the
      uptake of optional vaccinations of preschool children in Italy. METHODS:
      Interviews of Italian mothers were performed using a structured questionnaire
      administered by trained interviewers with no specific medical competence.
      RESULTS: A convenience sample of 1,035 mothers were interviewed. Fifty-nine
      percent of the respondents reported to have had their child immunized with the
      MMR vaccine and 54% reported to have had their child immunized against pertussis.
      In logistic regression analysis, three variables were significantly associated
      with both the immunization outcomes: mother's positive attitude toward
      immunization (OR = 1.69; IC 1.13-2.52 for pertussis; OR = 1.86, IC 1. 17-2.96 for
      MMR); mothers' residency in the North of the country (OR = 1.74; IC 1.32-2.30 for
      pertussis; OR = 1.63, IC 1.18-2.24 for MMR); and mother's receipt of satisfactory
      information on immunization (OR = 1.67; IC 1.15-2.21 for pertussis; OR = 2.25, IC
      1. 47-3.43 for MMR). An immunization performed in recent years (after 1994),
      probably following the widespread use of acellular vaccine, was the most
      significant predictor for pertussis immunization (OR = 3.21; IC 2.43-4.24).
      CONCLUSIONS: The findings suggest that mothers' attitudes, educational level, and
      socio-demographic characteristics, as well as socio-economic factors and local
      health policies, can influence children's immunization uptake. Health promotion,
      based on a partnership between parents and health professionals, should become a
      priority in Italian vaccination policies.

PMID- 10896844
TI  - Measurement of dietary intake in the UNC Alumni Heart Study. University of North
      Carolina.
AB  - BACKGROUND: Research needs to identify diet and disease associations to provide
      direction about effecting change in individuals with dietary behaviors that
      increase risk of chronic disease. Inclusion of dietary assessment in the
      University of North Carolina Alumni Heart Study (UNCAHS) provides the opportunity
      to prospectively investigate dietary intake and chronic disease associations with
      measures of personality and behavioral risk factors. METHODS: Development of the
      UNCAHS food frequency questionnaire and nutrient intake of 4,443 middle-aged men
      and women is provided stratified by total fat and vitamin A intake within
      demographic and health behavior categories. RESULTS: Alumni consume diets close
      to that recommended by current dietary guidelines. Both men and women have low
      calcium intake. Thirty-nine percent of the alumni consume diets with 30% of
      kilocalories from fat or less and 88% meet the RDA for vitamin A. Never smokers
      had lower fat diets and greater intakes of vitamin A than former or current
      smokers. Over 54% of alumni currently took vitamin/mineral supplements.
      CONCLUSIONS: UNCAHS participants will be tracked as they approach older ages with
      apparently less risk for diet-related chronic diseases than many Americans. The
      psychosocial correlates of these eating behaviors will be evaluated as disease
      endpoints occur.

PMID- 10896845
TI  - Free nicotine patches plus proactive telephone peer support to help low-income
      women stop smoking.
AB  - BACKGROUND: This study tested the impact of free nicotine patches plus proactive
      telephone peer support to help low-income women stop smoking. METHODS: A total of
      214 Medicaid-eligible women smokers of childbearing age were randomized to
      receive free nicotine patches through the mail or free nicotine patches through
      the mail plus the provision of proactive support by telephone from a woman ex
      smoker for up to 3 months. Assessments were conducted by telephone at baseline,
      10 days, and 3 and 6 months after enrollment. RESULTS: At the 3-month follow-up,
      significantly more women in the patch plus proactive telephone support condition
      were abstinent (42%) compared to the patch only condition (28%) (P = 0.03).
      Similarly, more women in the experimental condition were abstinent at both the 10
      day and 3-month assessments (32 v 19%, P = 0.02). However, differences were not
      found at the 6-month follow-up, suggesting that the addition of proactive
      telephone peer support enhanced short-term, but not long-term cessation.
      CONCLUSIONS: This is the first study to demonstrate a beneficial effect for the
      addition of proactive telephone support as an adjunct to free nicotine
      replacement in a low-income population.

PMID- 10896846
TI  - Prophylactic surgery decisions and surveillance practices one year following
      BRCA1/2 testing.
AB  - BACKGROUND: Although genetic testing for breast cancer risk is clinically
      available, its impact on health-related behaviors is unknown. This study examined
      prophylactic surgery and surveillance behavior during the year following BRCA1/2
      gene testing. METHODS: Participants were female members (n = 216) of hereditary
      breast-ovarian cancer families (84 mutation carriers, 83 noncarriers and 49 test
      decliners). In this prospective observational study, utilization of prophylactic
      surgery and surveillance behavior were assessed 1-year following BRCA1/2 testing.
      RESULTS: Only 3% of the unaffected carriers obtained prophylactic mastectomy
      during the 1-year follow-up period. Among the remaining females, carriers had
      significantly higher rates of mammography (68%) than noncarriers (44%); (OR =
      7.1; C.I. = 1.36-37.1; P = 0.02). However, the adherence rate in carriers was
      unchanged from baseline, suggesting that this difference is attributable to a
      reduction in screening among noncarriers. Women ages 25-39 years were
      significantly less likely to obtain mammograms than those aged 40 years and
      older. Cancer-related distress had a positive but nonsignificant (P < 0.07)
      association with adherence in bivariate but not multivariate analysis. With
      regard to ovarian risk, only 13% of carriers obtained prophylactic oophorectomy;
      of the remaining female carriers, only 21% reported a CA125 and 15% reported a
      transvaginal ultrasound. CONCLUSION: The vast majority of BRCA1/2 carriers may
      not opt for prophylactic surgery, and many do not adhere to surveillance
      recommendations. Greater attention to risk communication and medical decision
      making is warranted.

PMID- 10896847
TI  - Health-associated changes in drinking: a period prevalence study of the
      Atherosclerosis Risk In Communities (ARIC) cohort (1987-1995).
AB  - BACKGROUND: Several investigators have suggested that drinking cessation occurs
      because of poor health which may bias studies on the benefit or risk of alcohol
      consumption. METHODS: Drinking status, level of alcohol consumption, and two
      measures of health (perceived health and physician diagnosed chronic disease
      status) were determined from exams 1 (1987-1989) and 3 (1993-1995) on 12,562
      African- and European-American participants, who were aged 45-64 years at exam 1
      in the ARIC Study. For those in good health at exam 1, logistic regression
      analyses were used to model the association between health decline and drinking
      change at exam 3. RESULTS: Among the total population, drinking cessation was
      significantly more common among those who reported poor health at exam 3, and
      nondrinkers were unlikely to begin drinking regardless of exam 3 health. Using
      different measures of health status resulted in associations whose strength and
      significance varied with ethnicity and, in some cases, by gender. CONCLUSION:
      While the current data do not prove that the health decline occurred prior to
      drinking cessation, our findings support the hypothesis that poor health results
      in drinking changes which could potentially bias studies of alcohol's benefit and
      risk even when lifetime abstainers are used as the reference group.

PMID- 10896848
TI  - DNA damage cell checkpoint activities are altered in monocrotaline pyrrole
      induced cell cycle arrest in human pulmonary artery endothelial cells.
AB  - Monocrotaline pyrrole (MCTP) causes cyto- and karyomegaly and persistent cell
      cycle arrest in the G2 stage of the cell cycle in cultured bovine pulmonary
      artery endothelial cells. To better characterize the cell cycle regulatory
      mechanisms of this process as well as determine whether this process would occur
      in cells of human origin, we treated human pulmonary artery endothelial cell
      (HPAEC) cultures with MCTP and determined, by flow cytometry, the expression of
      cyclin B1 and p53 in conjunction with DNA content. We also validated by Western
      blots that the persistence of cdc2 in its inactivated phosphorylated state,
      previously described in bovine cell cultures, occurred in HPAEC. Alterations in
      p53, cyclin A, cyclin B1, and cdc25c expression were also examined in Western
      blots of treated HPAEC extracts. The response of HPAEC to MCTP was compared with
      that of adriamycin and nocodazole, agents known to cause cell cycle alterations.
      Results of these experiments demonstrate that HPAEC treated with MCTP develop a
      population of cells in G2 that has increased cyclin B1 expression. These cells
      express increased amounts of cdc2 but not cdc25c. The ratio of inactive
      triphosphorylated cdc2 to the active monophosphorylated form increased moderately
      from control cultures in contrast to predominance of the active form in
      nocodazole-treated cultures. In addition, a second population of cells expressing
      cyclin B1 had continued incorporation of BrdU and DNA content consistent with 8 N
      chromosomes. A similar 8 N cell population was evident in nocodazole-treated
      cells but these cells had both cyclin B1 positive and negative components.
      Compared with adriamycin, a known inducer of p53, MCTP-treated HPAEC expressed
      p53 only at high concentrations and p53 expression was not coordinated with G2
      arrest or polyploidy. We conclude that HPAEC treated with low concentrations of
      MCTP develop G2 arrest in association with persistent cyclin B1 expression,
      failure to completely activate cdc2, and continued DNA synthesis through a
      pathway that is unrelated to altered expression of p53.

PMID- 10896849
TI  - Electrophysiological and biochemical effects of single and multiple doses of the
      organophosphate diazinon in the mouse.
AB  - Diazinon is an organophosphorus compound (OP) widely used in pesticides. The
      relationship between dose of diazinon, inhibition of acetylcholinesterase, and
      effect on neuromuscular transmission has been studied in a mouse model.
      Inhibition of acetylcholinesterase activity occurred within 1 h, was maximal by 3
      h and remained inhibited for at least 24 h. Blood, brain, diaphragm, and soleus
      acetylcholinesterase activities were differentially affected by diazinon. Brain
      and soleus activities were not affected by low doses. Multiple daily dosing of
      diazinon caused a cumulative decrease in acetylcholinesterase activity, although
      to a lesser extent in brain and soleus. Diazinon had no effect on the activity of
      neuropathy target esterase. Plasma and brain levels of diazinon peaked at 15 min
      after dosing and declined with a half-life of 2.5 h. Metabolic products of
      diazinon were cleared from the urine within 24 h. Increased miniature end-plate
      current half decay times occurred in a dose-dependent manner. Single doses of
      diazinon caused an increase in the jitter (variability of latencies) of evoked
      action potentials recorded in the diaphragm but did not affect end-plate
      potential (EPP) jitter. Multiple lower doses of diazinon caused an increase in
      EPP jitter after 28 days. This effect on nerve function was delayed and occurred
      when acetylcholinesterase activity had returned to control levels. The results
      indicate that diazinon produces long-term electrophysiological changes in
      neurotransmission following repeated dosing in the mouse. This has implications
      for the current use of diazinon; however, there is a need to further define the
      mechanism of this effect.

PMID- 10896850
TI  - Enhanced hepatotoxicity and toxic outcome of thioacetamide in streptozotocin
      induced diabetic rats.
AB  - Diabetes is known to potentiate thioacetamide (TA)-induced liver injury via
      enhanced bioactivation. Little attention has been given to the role of
      compensatory tissue repair on ultimate outcome of hepatic injury in diabetes. The
      objective of this study was to investigate the effect of diabetes on TA-induced
      liver injury and lethality and to investigate the underlying mechanisms. We
      hypothesized that hepatotoxicity of TA in diabetic rats would increase due to
      enhanced bioactivation-mediated liver injury and also due to compromised
      compensatory tissue repair, consequently making a nonlethal dose of TA lethal. On
      day 0, male Sprague-Dawley rats (250-300 g) were injected with streptozotocin
      (STZ, 60 mg/kg ip) to induce diabetes. On day 10 the STZ-induced diabetic rats
      and the nondiabetic rats received a single dose of TA (300 mg/kg ip). This
      normally nonlethal dose of TA caused 90% mortality in the STZ-induced diabetic
      rats. At various times (0-60 h) after TA administration, liver injury was
      assessed by plasma alanine aminotransferase (ALT), sorbitol dehydrogenase (SDH),
      and liver histopathology. Liver function was evaluated by plasma bilirubin. Cell
      proliferation and tissue repair were evaluated by [(3)H]thymidine ((3)H-T)
      incorporation and proliferating cell nuclear antigen (PCNA) assays. In the
      nondiabetic rat, liver necrosis peaked at 24 h and declined thereafter toward
      normal by 60 h. In the STZ-induced diabetic rat, however, liver necrosis was
      significantly increased from 12 h onward and progressed, culminating in liver
      failure and death. Liver tissue repair studies showed that, in the liver of
      nondiabetic rats, S-phase DNA synthesis was increased at 36 h and peaked at 48 h
      following TA administration. However, DNA synthesis was approximately 50%
      inhibited in the liver of diabetic rats. PCNA study showed a corresponding
      decrease of cell-cycle progression, indicating that the compensatory tissue
      repair was sluggish in the diabetic rats. Further investigation of tissue repair
      by employing equitoxic doses (300 mg TA/kg in the non-diabetic rats; 30 mg TA/kg
      in the diabetic rats) revealed that, despite equal injury up to 24 h following
      injection, the tissue repair response in the diabetic rats was much delayed. The
      compromised tissue repair prolonged liver injury in the diabetic rats. These
      studies suggest that the increased TA hepatotoxicity in the diabetic rat is due
      to combined effects of increased bioactivation-mediated liver injury of TA and
      compromised compensatory tissue repair.

PMID- 10896851
TI  - Activation of NF-kappaB by PM(10) occurs via an iron-mediated mechanism in the
      absence of IkappaB degradation.
AB  - Exposure to particulate air pollution (PM(10)) is associated with exacerbations
      of respiratory diseases and increased cardiopulmonary mortality. PM(10) induces
      lung inflammation in rats, which has been attributed to many factors, including
      the ultrafine components of PM(10), endotoxins, and transition metals. In this
      study, we investigated in alveolar epithelial (A549) cells whether PM(10) could
      activate nuclear factor-kappa B (NF-kappaB), a transcription factor stimulated in
      response to many proinflammatory agents. Our results show that PM(10) samples
      from various sites within the United Kingdom cause nuclear translocation, DNA
      binding, and transcriptional activation of NF-kappaB in A549 cells. Furthermore,
      increased NF-kappaB activity was observed in the absence of IkappaB degradation.
      To evaluate the role of iron, A549 cells were exposed to PM(10) previously
      treated with phosphate-buffered saline (PBS), deferoxamine mesylate, or
      deferoxamine plus ferrozine. PBS-treated and, to a lesser extent, deferoxamine
      treated PM(10) were able to activate NF-kappaB, whereas this response was
      completely abrogated in cells exposed to PM(10) treated with both deferoxamine
      and ferrozine. Moreover, we studied the effects of soluble components of PM(10)
      on NF-kappaB activation by exposing alveolar epithelial cells to soluble
      fractions from PM(10) treated with PBS or the metal chelators. We found that,
      compared with fractions from PBS-treated PM(10) which activated NF-kappaB,
      fractions from PM(10) treated with deferoxamine and ferrozine did not stimulate
      NF-kappaB activity above background levels. Coincubation of polymixin B, an
      endotoxin-binding compound, and PM(10) did not inhibit NF-kappaB. In summary,
      PM(10) activates NF-kappaB in A549 cells by an iron-mediated mechanism in the
      absence of IkappaB degradation.

PMID- 10896852
TI  - Zinc is the toxic factor in the lung response to an atmospheric particulate
      sample.
AB  - The atmospheric dust sample EHC-93 is known to induce lung cell injury and
      inflammation in which the toxicity has been attributed to a soluble component,
      possibly metal ions. To determine whether any specific metal is responsible for
      the pulmonary reactivity, various metal salts, at the concentration of metal
      present in the soluble fraction of EHC dust, have now been instilled into mouse
      lung. After 3 days, only a solution containing all metals tested and that of a
      zinc salt alone induced an increase in inflammatory cells and protein in lung
      lavage fluid. These two solutions also increased DNA synthesis in lung cells at
      this time, indicating a reparative response. Other solutions containing metals
      such as Cu, Fe, Al, Pb, Mg, or Ni induced no changes in the preceding
      measurements at the EHC dose level of metal. In a more extensive 28-day study,
      zinc salts induced rapid focal necrosis of Type 1 alveolar epithelial cells
      followed by inflammation and elevation of protein levels in lavage fluid over a 2
      week period. Following the injury, epithelial cell proliferation increased and
      focal fibrosis was seen at 4 weeks. A solution containing all the other metals
      tested without the zinc component induced only minimal lung effects. When a zinc
      salt was administered at a 10x dose, the pulmonary changes were greatly enhanced,
      and after 4 weeks fibrosis could be measured biochemically. The results indicate
      that the acute toxicity associated with EHC atmospheric dust is most likely the
      result of the level of soluble zinc in this particulate sample. This suggests
      that a high soluble metal content of atmospheric dust, in this case the zinc
      level, may be a crucial factor in determining pulmonary cell reactivity to
      inhaled particulates.

PMID- 10896853
TI  - Chlorophyllin suppression of lipopolysaccharide-induced nitric oxide production
      in RAW 264.7 cells.
AB  - Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, functions as an
      anticarcinogen and antioxidant. In the present study, we investigated the effect
      of CHL on nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW
      264.7 cells. Treatment with CHL inhibited nitric oxide production in the LPS
      stimulated RAW 264. 7 cells in a dose-related manner. Competitive RT-PCR
      analysis, using a DNA competitor as an internal standard, demonstrated that the
      treatment with 1, 10, and 50 microM CHL decreased LPS-induced iNOS mRNA
      expression in a concentration-dependent manner. Since the expression of the iNOS
      gene is mainly regulated by NF-kappaB, we then examined the effects of CHL on the
      NF-kappaB DNA binding activity, using an electrophoretic mobility shift assay.
      CHL down-regulated the NF-kappaB DNA binding on its cognate recognition site at
      the concentrations just noted. Employing a transfection and reporter gene
      expression system with p(NF-kappaB)(3)-chloramphenicol acetyl transferase (CAT),
      the treatment of CHL produced a dose-dependent inhibition of CAT activity in RAW
      264.7 cells. Furthermore, CHL partially restored LPS-decreased IkappaBalpha, an
      inhibitory protein against NF-kappaB activation, in the cytosolic extract from
      the LPS-treated cells determined by immunoblot analysis. CHL also protected the
      hydroxyl radical-induced cytotoxicity in RAW 264.7 cells, indicating its
      antioxidant effect. These results suggest that CHL suppresses the nitric oxide
      production and iNOS mRNA expression mediated by the inhibition of NF-kappaB
      activation, and its action mechanism may be based on its antioxidant effect.

PMID- 10896854
TI  - A physiologically based pharmacodynamic analysis of hepatic foci within a medium
      term liver bioassay using pentachlorobenzene as a promoter and diethylnitrosamine
      as an initiator.
AB  - A stochastic clonal growth model for describing quantitative changes in size and
      number of putative preneoplastic lesions was modified to analyze the time-course
      information of cell proliferation and glutathione S-transferase pi (GST-P) foci
      within a medium-term bioassay. The study used F344 rats and a single initiating
      event using diethylnitrosamine (200 mg/kg ip) at Week 0. After a 2-week recovery
      period, chemical treatment began by gavage administration of pentachlorobenzene
      (PeCB; 100 micromol/kg/day, 7 days/week) in a corn oil vehicle and continued for
      6 weeks. One week after beginning gavage dosing, a two-thirds partial hepatectomy
      was performed and the animals were serially euthanized at 48, 120, 168, 624, and
      840 h postsurgery, which corresponds to 216, 288, 336, 792, and 1008 h following
      the beginning of PeCB treatment, respectively. For analysis, two types of models
      were evaluated for describing the time-course changes in GST-P foci. First, a
      sequential model describing the transformation of normal cells into a homogenous
      initiated cell population (i.e., one-cell model). Second, a two-cell model that
      describes a heterogeneous foci population by splitting the initiated cell
      population into two distinct types. In our study, the one-cell model was unable
      to adequately represent the time-course data for changes in both size and number
      of foci. In contrast, the two-cell model, which was parameterized to describe a
      negative selection mechanism, produced adequate simulations of both the size and
      number of foci. This model-based analysis suggested that the differences between
      PeCB-treated and untreated animals were primarily in parameters involving the
      rates of cell death.

PMID- 10896855
TI  - Validation of negligible depletion solid-phase microextraction as a tool to
      determine tissue/blood partition coefficients for semivolatile and nonvolatile
      organic chemicals.
AB  - In the current study, negligible depletion solid-phase microextraction (nd-SPME)
      as a technique to determine tissue/blood (tissue/water and blood/water) partition
      coefficients was validated. With this method the free fraction of chemicals in
      water in the presence of different tissues was determined and, subsequently, the
      partition coefficients were calculated. Liver, blood, muscle, and fat tissues
      obtained from male Wistar-derived rats (U:Wu) were used without homogenization.
      Data obtained were compared with literature data for lindane, parathion, and
      paraoxon. The results show that the data in the present work differ by less than
      a factor of two from those reported in literature. In addition, the standard
      deviations obtained show that the technique is accurate. Therefore, we conclude
      that this accurate and automated method can be used to determine tissue/blood
      partition coefficients for semivolatile and nonvolatile chemicals.

PMID- 10896856
TI  - Hepatoprotection by dimethyl sulfoxide. III. Role of inhibition of the
      bioactivation and covalent bonding of chloroform.
AB  - Dimethyl sulfoxide (DMSO) has previously been shown to have the ability to
      attenuate chloroform (CHCl(3))-induced liver injury in the naive rat even when
      administered 24 h after the toxicant. These studies were undertaken to determine
      if the protective action by late administration of DMSO is due to an inhibition
      of the bioactivation of CHCl(3). This was done by comparing the cytochrome P450
      inhibitors, diallyl sulfide (DAS), and aminobenzotriazole (ABT) to DMSO for their
      protective efficacy when administered 24 h after CHCl(3) exposure. In addition,
      (14)CHCl(3) was utilized to measure the effect of DMSO and ABT on the covalent
      binding of CHCl(3) in the liver following their late administration. Male Sprague
      Dawley rats (300-350 g) received 0.75 ml/kg CHCl(3) po. Twenty-four hours later,
      they received ip injection of 2 ml/kg DMSO, 100 mg/kg DAS, or 30 mg/kg ABT.
      Plasma ALT activities and quantitation of liver injury by light microscopy at 48
      h after CHCl(3) dosing indicated that all three treatments were equally effective
      at protecting the liver. A detailed study of the time course of injury
      development indicated that the protective action of DMSO was occurring within 10
      h of its administration. Therefore, in the radiolabel studies, rats were killed
      24-34 h after receiving 0.75 ml/kg CHCl(3) (30 microCi/kg (14)CHCl(3)) po.
      Treatment with ABT at 24 h after (14)CHCl(3) dosing decreased the covalent
      binding of (14)C to hepatic protein by 35% and reduced the amount of (14)C in the
      blood by 50% by 10 h after its administration. DMSO treatment did not
      significantly affect any of these parameters. The lack of effect by late
      administration of DMSO on the covalent binding of CHCl(3) would indicate that
      DMSO may offer protection by mechanisms other than inhibition of the
      bioactivation of CHCl(3). These studies also indicate that specific cytochrome
      P450 inhibitors may be of benefit in clinical situations to help treat the
      delayed onset hepatitis that can result following poisoning with an
      organohalogen, even if the antidotes are administered a number of hours after the
      initial exposure.

PMID- 10896857
TI  - Multiple comparisons: philosophies and illustrations.
AB  - Statistical procedures underpin the process of scientific discovery. As
      researchers, one way we use these procedures is to test the validity of a null
      hypothesis. Often, we test the validity of more than one null hypothesis. If we
      fail to use an appropriate procedure to account for this multiplicity, then we
      are more likely to reach a wrong scientific conclusion-we are more likely to make
      a mistake. In physiology, experiments that involve multiple comparisons are
      common: of the original articles published in 1997 by the American Physiological
      Society, approximately 40% cite a multiple comparison procedure. In this review,
      I demonstrate the statistical issue embedded in multiple comparisons, and I
      summarize the philosophies of handling this issue. I also illustrate the three
      procedures-Newman-Keuls, Bonferroni, least significant difference-cited most
      often in my literature review; each of these procedures is of limited practical
      value. Last, I demonstrate the false discovery rate procedure, a promising
      development in multiple comparisons. The false discovery rate procedure may be
      the best practical solution to the problems of multiple comparisons that exist
      within physiology and other scientific disciplines.

PMID- 10896858
TI  - Critical oxygen tension in rat brain: a combined (31)P-NMR and EPR oximetry
      study.
AB  - The relationship between cerebral interstitial oxygen tension (Pt(O(2))) and
      cellular energetics was investigated in mechanically ventilated, anesthetized
      rats during progressive acute hypoxia to determine whether there is a "critical"
      brain Pt(O(2)) for maintaining steady-state aerobic metabolism. Cerebral
      Pt(O(2)), measured by electron paramagnetic resonance oximetry, decreased
      proportionately to inspired oxygen fraction. (31)P-nuclear magnetic resonance
      measurements revealed no changes in P(i), phosphocreatine (PCr)/P(i) ratio, or
      intracellular pH when arterial blood oxygen tension (Pa(O(2))) was reduced from
      145.1 +/- 11.7 to 56.5 +/- 4.4 mmHg (means +/- SE). Intracellular acidosis, a
      sharp rise in P(i), and a decline in the PCr/P(i) ratio developed when Pa(O(2))
      was reduced further to 40.7 +/- 2.3 mmHg. The corresponding Pt(O(2)) values were
      15.1 +/- 1.8, 8.8 +/- 0.4, and 6.8 +/- 0.3 mmHg. We conclude that over a range of
      decreasing oxygen tensions, cerebral oxidative metabolism is not sensitive to
      oxygen concentration. Oxygen becomes a regulatory substrate, however, when
      Pt(O(2)) is decreased to a critical level.

PMID- 10896859
TI  - Renal Na excretion in dehydrated and rehydrated adrenalectomized sheep maintained
      with aldosterone.
AB  - The effect of water deprivation for 19 h on renal Na excretion of conscious
      adrenalectomized (ADX) sheep maintained on a constant intravenous infusion of
      aldosterone and cortisol (ADX-constant steroid sheep) was investigated. Both ADX
      and normal sheep showed large increases in renal Na excretion when they were
      deprived of water. ADX-constant steroid sheep also exhibited a normal
      postprandial natriuresis 3-6 h after feeding, whether or not water was available
      to drink. In another experiment, sheep deprived of water for 41 h were then
      allowed to drink water. Both normal and ADX-constant steroid sheep exhibited a
      large reduction of renal Na excretion in the 6 h after rehydration. Changes in
      plasma Na and K concentration and osmolality were similar in normal and ADX
      constant steroid sheep during periods of dehydration and rehydration. These
      results show that change in aldosterone secretion is not a major factor in
      causing either dehydration-induced or postprandial natriuresis. Neither is it a
      major cause of rehydration-induced renal Na retention.

PMID- 10896860
TI  - Receptor-specific influence of endothelin-1 in the erectile response of the rat.
AB  - Specific receptor antagonists were used to examine the role of endothelin-1 (ET
      1) in the erectile response of the rat. In these studies, intact rats were
      cannulated to permit the continuous recording of mean arterial pressure (MAP) and
      intracavernosal pressure (CCP). Erection was induced by electrical stimulation of
      the autonomic ganglion, which regulates blood flow to the penis. The animals were
      subjected to intracavernosal injection with vehicle only (Cont) or with an
      antagonist to the endothelin-A receptor (ET(A)) or to the endothelin-B receptor
      (ET(B)). Blockade of the ET(A) or the ET(B) had no effect on the erectile
      response (CCP/MAP) during maximal ganglionic stimulation. When ET-1 was injected
      into Cont rats, there was a marked vasoconstriction with a sharp rise in MAP and
      a decline in CCP as the cavernosal arterioles constricted and limited inflow. The
      injection of the ET(A) antagonist prevented the vasoconstriction after ET-1
      injection into Cont rats, whereas blockade of the ET(B) had no effect on the
      vasoconstrictive effect to ET-1. Similar results were obtained during submaximal
      ganglionic stimulation. With minimal levels of ganglionic stimulation, ET-1
      injection led to a moderated degree of vasodilation in the presence of the ET(A)
      antagonist. The ET(B) antagonist failed to alter the CCP response during minimal
      stimulation, but it did have a marked effect on the MAP response to ET-1
      injection. The results of these studies confirm that cavernosal tissue of the rat
      penis is highly responsive to ET-1. However, the failure of the ET-1 antagonists
      to affect penile erection in response to ganglionic stimulation reflects a
      minimal role of ET-1 in the erectile response in the rat.

PMID- 10896861
TI  - Reduced fetal, placental, and amniotic fluid PTHrP in the growth-restricted
      spontaneously hypertensive rat.
AB  - Evidence implicates pivotal roles for parathyroid hormone-related protein (PTHrP)
      in stimulating cell growth and differentiation, placental calcium transport, and
      placental vasodilatation. As spontaneously hypertensive rat (SHR) fetuses are
      growth restricted compared with those of its normotensive control, the Wistar
      Kyoto (WKY) rat, we examined intrauterine PTHrP and total and ionic calcium
      concentrations in these rats. Fetal plasma PTHrP concentrations, but not total
      calcium concentrations, were lower in the SHR compared with WKY (P < 0.05). SHR
      placental concentrations of PTHrP were lower than in WKY (P < 0.03) and failed to
      show the increase observed in WKY near term (P < 0.05). PTHrP concentrations in
      amniotic fluid from SHR were not raised near term and were lower compared with
      WKY (P < 0.0005). The increased ionic calcium concentrations in amniotic fluid in
      the WKY near term (P < 0.05) were not detected in the SHR. Thus SHR fetal plasma,
      placental, and amniotic fluid PTHrP concentrations were reduced and associated
      with fetal growth restriction. We suggest that PTHrP may play a role in the
      etiology of both growth restriction during pregnancy and hypertension later in
      life.

PMID- 10896862
TI  - Postnatal age influences the ability of rats to autoresuscitate from hypoxic
      induced apnea.
AB  - Failure to autoresuscitate from apnea by gasping has been suggested to have a
      role in sudden infant death. Little is known, however, about the factors that
      influence the ability of gasping to sustain life during acute hypoxia in the
      newborn. The present experiments were carried out on 105 rat pups to investigate
      the influence of postnatal age on the time to last gasp during a single hypoxic
      exposure and on the ability to autoresuscitate from primary apnea during repeated
      hypoxic exposures. On days 1-2, 5-6, 10-11, 15-16, and 19-20 postpartum, each pup
      was placed into a temperature-controlled chamber regulated to 37 +/- 1 degrees C
      and was exposed either to a single period of hypoxia produced by breathing an
      anoxic gas mixture (97% N(2)-3% CO(2)), and the time to last gasp was determined,
      or repeated exposure to hypoxia was performed, and the ability to autoresuscitate
      from primary apnea was determined. Increases in postnatal age decreased the time
      to last gasp following a single hypoxic exposure and decreased the number of
      successful autoresuscitations following repeated hypoxic exposures. Thus our data
      provide evidence that postnatal age influences protective responses that may
      prevent death during hypoxia as may occur during episodes of prolonged sleep
      apnea.

PMID- 10896863
TI  - Long-term orexigenic effects of AgRP-(83---132) involve mechanisms other than
      melanocortin receptor blockade.
AB  - Overexpression of agouti-related peptide (AgRP), an endogenous melanocortin (MC)
      3 and 4 receptor antagonist (MC3/4-R), causes obesity. Exogenous AgRP-(83---132)
      increases food intake, but its duration and mode of action are unknown. We report
      herein that doses as low as 10 pmol can have a potent effect on food intake of
      rats over a 24-h period after intracerebroventricular injection. Additionally, a
      single third ventricular dose as low as 100 pmol in rats produces a robust
      increase in food intake that persists for an entire week. AgRP-(83---132)
      completely blocks the anorectic effect of MTII (MC3/4-R agonist), given
      simultaneously, consistent with a competitive antagonist action. However, when
      given 24 h prior to MTII, AgRP-(83---132) is ineffective at reversing the
      anorectic effects of the agonist. These results support a critical role of MC
      tone in limiting food intake and indicate that the orexigenic effects of AgRP-(83
      --132) are initially mediated by competitive antagonism at MC receptors but are
      sustained by alternate mechanisms.

PMID- 10896864
TI  - Effects of chronic reduction in uterine blood flow on fetal and placental growth
      in the sheep.
AB  - Pregnancy is associated with a significant increase in uteroplacental blood flow
      (UBF), which is responsible for delivering adequate nutrients and oxygen for
      fetal and placental growth. The present study was designed to determine the
      effects of vascular insufficiency on fetal and placental growth. Thirty-nine late
      term pregnant ewes were instrumented to investigate the effects of chronic UBF
      reduction. Animals were split into three groups based on uterine blood flow, and
      all animals were killed on gestational day 138. UBF, which began at 851 +/- 74
      ml/min (n = 39), increased in controls (C) to 1,409 +/- 98 ml/min (day 138 of
      gestation) and in the moderately restricted (R(M)) group to 986 +/- 69 ml/min. In
      the severely restricted (R(S)) group, UBF was only 779 +/- 79 ml/min on
      gestational day 138. This reduction in UBF significantly affected fetal body
      weight with R(M) fetuses weighing 3,685 +/- 178 g and R(S) fetuses weighing 2,920
      +/- 164 g compared with C fetal weights of 4,318 +/- 208 g. Fetal brain weight
      was not affected, whereas ponderal index was significantly reduced in R(M) (2.94
      +/- 0.09) and R(S) fetuses (2.49 +/- 0.08) compared with the value of the C
      fetuses (3.31 +/- 0.08). Placental weight was also significantly reduced in the
      R(M) group, being 302 +/- 24 g, whereas the R(S) group placenta weighed 274 +/-
      61 g compared with the C values of 414 +/- 57 g. Fetal heart, liver, lung, and
      thymus were all significantly smaller in the R(S) group. Thus the present study
      shows a clear relationship between the level of UBF and both fetal and placental
      size. Furthermore, the observation that fetal brain weight was not affected,
      whereas fetal body weight was significantly reduced suggests that this
      experimental preparation may provide a useful model in which to study asymmetric
      fetal growth restriction.

PMID- 10896865
TI  - Regulation of urinary bladder smooth muscle contractions by ryanodine receptors
      and BK and SK channels.
AB  - This study examines the roles of voltage-dependent Ca(2+) channels (VDCC),
      ryanodine receptors (RyRs), large-conductance Ca(2+)-activated K(+) (BK)
      channels, and small-conductance Ca(2+)-activated K(+) (SK) channels in the
      regulation of phasic contractions of guinea pig urinary bladder smooth muscle
      (UBSM). Nisoldipine (100 nM), a dihydropyridine inhibitor of VDCC, abolished
      spontaneous UBSM contractions. Ryanodine (10 microM) increased contraction
      frequency and thereby integrated force and, in the presence of the SK blocker
      apamin, had a greater effect on integrated force than ryanodine alone. Blocking
      BK (iberiotoxin, 100 nM) or SK (apamin, 100 nM) channels increased contraction
      amplitude and duration but decreased frequency. The contractile response to
      iberiotoxin was more pronounced than to apamin. The increases in contraction
      amplitude and duration to apamin were substantially augmented with ryanodine
      pretreatment. These results indicate that BK and SK channels have prominent roles
      as negative feedback elements to limit UBSM contraction amplitude and duration.
      RyRs also appear to play a significant role as a negative feedback regulator of
      contraction frequency and duration, and this role is influenced by the activity
      of SK channels.

PMID- 10896866
TI  - Osmolyte channel regulation by ionic strength in skate RBC.
AB  - The aim of this study was to determine whether the opening of the osmolyte
      channel in skate red blood cells (RBC) is regulated by intracellular electrolyte
      concentration and conductivity. Consistent with previous studies, experiments
      with hyperosmotic preincubation before cell swelling or swelling with an
      isosmotic electrolyte (e.g., ammonium chloride) showed that an increase in ionic
      strength inhibits the opening of the taurine channel. However, a decrease in
      intracellular ionic strength did not always stimulate taurine efflux to the same
      degree. Whereas hyposmotic swelling caused a large increase in taurine efflux,
      swelling induced by treatment with isosmotic nonelectrolytes produced much
      smaller stimulation. Results with assays for band 3 phosphorylating enzymes were
      consistent with those from the taurine efflux studies; stimulation of enzyme
      activity was lower in cells that were swollen with isosmotic nonelectrolyte media
      than in cells swollen in hyposmotic media. These results indicate that a decrease
      in ionic strength is not the only signal for the opening of the taurine channel
      in skate RBC. Ionic strength does affect channel activity, but there must also be
      some other regulator.

PMID- 10896867
TI  - Changes in cardiac mechanics with heat acclimation: adrenergic signaling and SR
      Ca regulatory proteins.
AB  - The involvement of adrenergic signaling and sarcoplasmic calcium regulatory
      proteins in the development of heat acclimation-induced adaptations in cardiac
      mechanics was studied in heat-acclimated (34 degrees C) rats for 2, 5, and 30
      days (AC(2), AC(5), and AC(30), respectively). Control (C) rats were held at 24
      +/- 1 degrees C. Systolic pressure (LVP) and velocities of contraction (dP/dt/P)
      and relaxation (-dP/dt/P) were measured using a Langendorff system. For
      adrenergic signaling, beta-adrenoreceptor (AR) density and affinity (Scatchard
      plots) and cardiac inotropic response to norepinephrine (10(-7) mM, +/- 10(-6) mM
      propranolol) were measured. For the regulatory proteins, steady-state levels of
      Ca(2+)-ATPase and phospholamban (PLB) mRNAs and the encoded proteins Ca(2+)
      ATPase [sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)] and PLB were measured
      using semiquantitative RT-PCR and Western immunoblotting, respectively. Both
      short (STHA; AC(2) and AC(5))- and long-term heat acclimation (LTHA; AC(30))
      enhanced LVP. However, dP/dt. P and -dP/dt. P in STHA hearts resembled that of
      the controls, whereas on LTHA, both parameters decreased (P < 0.05), implying
      decreased velocity of contraction and relaxation. beta-AR density remained
      unchanged with their affinity markedly decreased (P < 0.05). AR responsiveness,
      however, diminished in AC(2) but was markedly enhanced on LTHA. During STHA, PLB
      and sarcoplasmic reticulum Ca(2+)-ATPase transcripts were upregulated with no
      change in the encoded proteins except for SERCA downregulation on AC(5), leading
      to an increased PLB/SERCA ratio (P < 0.05). This mismatched preacclimation
      lusitropic state on STHA and increased PLB/SERCA ratio was evident (P < 0.05) due
      to downregulation of SERCA and upregulation of PLB. Our data fit a biphasic
      acclimation model in which desensitized adrenergic signaling is dominant during
      STHA, whereas on LTHA, the contractile machinery is influenced by altered
      expression of the calcium regulatory proteins leading to both augmented
      adrenergic inotropic response (via PLB elevation) and decreased velocity of
      relaxation. The sustained low thyroxin measured on LTHA causally associates with
      this response.

PMID- 10896868
TI  - Naltrexone administered to central nucleus of amygdala or PVN: neural
      dissociation of diet and energy.
AB  - There is evidence that opioids may affect food consumption through mechanisms as
      diverse as reward or energy metabolism. However, these hypotheses are derived
      from studies employing peripheral or, more rarely, intracerebroventricular
      administration of drugs. Opioid receptors have a wide distribution in the central
      nervous system and include a number of regions implicated in food intake such as
      the hypothalamic paraventricular nucleus (PVN) and the central nucleus of the
      amygdala (ACe). It is not known whether local opioid receptor blockade in either
      of these regions will produce similar effects on food intake. To examine this
      issue, a chronic cannula was aimed at either the PVN or ACe of rats that were fed
      a choice of a high-fat and high-carbohydrate diet, which allows for the
      measurement of both preference and total energy consumption. Naltrexone
      influenced preferred and nonpreferred food consumption, depending on the site of
      administration. Consumption of both preferred and nonpreferred diets was
      suppressed after PVN naltrexone administration, whereas only preferred diet
      intake was reduced after ACe injection of naltrexone. The present evidence
      indicates that direct stimulation of different brain regions with naltrexone may
      be associated with diverse effects on diet selection, which may be accounted for
      by manipulation of specific functional neural circuitry.

PMID- 10896869
TI  - Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine
      expression.
AB  - The present study was designed to determine the role of endogenous brain
      interleukin (IL)-1 in the anorexic response to lipopolysaccharide (LPS).
      Intraperitoneal administration of LPS (5-10 microgram/mouse) induced a dramatic,
      but transient, decrease in food intake, associated with an enhanced expression of
      proinflammatory cytokine mRNA (IL-1beta, IL-6, and tumor necrosis factor-alpha)
      in the hypothalamus. This dose of LPS also increased plasma levels of IL-1beta.
      Intracerebroventricular pretreatment with IL-1 receptor antagonist (4
      microgram/mouse) attenuated LPS-induced depression of food intake and totally
      blocked the LPS-induced enhanced expression of proinflammatory cytokine mRNA
      measured in the hypothalamus 1 h after treatment. In contrast, LPS-induced
      increases in plasma levels of IL-1beta were not altered. These findings indicate
      that endogenous brain IL-1 plays a pivotal role in the development of the
      hypothalamic cytokine response to a systemic inflammatory stimulus.

PMID- 10896870
TI  - Brief hypoxic stress suppresses postbacteremic NF-kappaB activation and TNF-alpha
      bioactivity in perfused liver.
AB  - Reductions in hepatic O(2) delivery are common early after gram-negative
      bacteremic sepsis owing to cardiopulmonary dysfunction and derangements in
      sinusoidal perfusion. Although gram-negative endotoxin and cellular hypoxia
      independently enhance activation of nuclear factor-kappaB (NF-kappaB) via
      generation of reactive O(2) species (ROS), the combination of these stimuli
      downregulates hepatic TNF-alpha gene expression. Here we tested the hypothesis
      that hypoxic suppression of postbacteremic TNF-alpha gene expression is
      transcriptionally mediated by reduced activation of NF-kappaB. Buffer-perfused
      rat livers (n = 52) were studied over 180 min after intraportal infection at t =
      0 with 10(9) live Escherichia coli (EC), serotype O55:B5, or 0.9% NaCl controls
      under normoxic conditions, compared with 0.5 h of constant-flow hypoxia (PO(2)
      approximately 41 +/- 7 Torr) beginning at t = 30 min, followed by 120 min of
      reoxygenation. In parallel studies, tissue was obtained at peak hypoxia (t = 60
      min). To determine the role of xanthine oxidase (XO)-induced ROS in modulating NF
      kappaB activity after hypoxia/reoxygenation (H/R), livers were pretreated with
      the XO inhibitor allopurinol, with results confirmed in organs of tungstate-fed
      animals. Electrophoretic mobility shift assays were performed on nuclear extracts
      of whole liver lysates using (32)P-labeled oligonucleotides specific for NF
      kappaB. Compared with normoxic EC controls, hypoxia reduced postbacteremic NF
      kappaB nuclear translocation and TNF-alpha bioactivity, independent of
      reoxygenation, tissue levels of reduced glutathione, or posthypoxic O(2)
      consumption. XO inhibition reversed the hypoxic suppression of NF-kappaB nuclear
      translocation and ameliorated decreases in cell-associated TNF-alpha. Thus
      decreases in hepatic O(2) delivery reduce postbacteremic nuclear translocation of
      NF-kappaB and hepatic TNF-alpha biosynthesis by signaling mechanisms involving
      low-level generation of XO-mediated ROS.

PMID- 10896871
TI  - Anatomic patterning in the expression of vestibulosympathetic reflexes.
AB  - To investigate the possibility that expression of vestibulosympathetic reflexes
      (VSR) is related to a nerve's anatomic location rather than its target organ, we
      compared VSR recorded from the same type of postganglionic fiber [muscle
      vasoconstrictor (MVC)] located at three different rostrocaudal levels: hindlimb,
      forelimb, and face. Experiments were performed on chloralose-anesthetized cats,
      and vestibular afferents were stimulated electrically. Single MVC unit activity
      was extracted by spike shape analysis of few-fiber recordings, and unit
      discrimination was confirmed by autocorrelation. Poststimulus time histogram
      analysis revealed that about half of the neurons were initially inhibited by
      vestibular stimulation (type 1 response), whereas the other MVC fibers were
      initially strongly excited (type 2 response). MVC units with types 1 and 2
      responses were present in the same nerve fascicle. Barosensitivity was equivalent
      in the two groups, but fibers showing type 1 responses fired significantly faster
      than those giving type 2 responses (0.29 +/- 0.04 vs. 0.20 +/- 0.02 Hz). Nerve
      fibers with type 1 responses were most common in the hindlimb (21 of 29 units)
      and least common in the face (2 of 11 units), the difference in relative
      proportion being significant (P < 0.05, chi(2) test). These results support the
      hypothesis that VSR are anatomically patterned.

PMID- 10896872
TI  - Vestibular stimulation leads to distinct hemodynamic patterning.
AB  - Previous studies demonstrated that responses of a particular sympathetic nerve to
      vestibular stimulation depend on the type of tissue the nerve innervates as well
      as its anatomic location. In the present study, we sought to determine whether
      such precise patterning of vestibulosympathetic reflexes could lead to specific
      hemodynamic alterations in response to vestibular afferent activation. We
      simultaneously measured changes in systemic blood pressure and blood flow (with
      the use of Doppler flowmetry) to the hindlimb (femoral artery), forelimb
      (brachial artery), and kidney (renal artery) in chloralose-urethane-anesthetized,
      baroreceptor-denervated cats. Electrical vestibular stimulation led to depressor
      responses, 8 +/- 2 mmHg (mean +/- SE) in magnitude, that were accompanied by
      decreases in femoral vasoconstriction (23 +/- 4% decrease in vascular resistance
      or 36 +/- 7% increase in vascular conductance) and increases in brachial vascular
      tone (resistance increase of 10 +/- 6% and conductance decrease of 11 +/- 4%).
      Relatively small changes (<5%) in renal vascular tone were observed. In contrast,
      electrical stimulation of muscle and cutaneous afferents produced pressor
      responses (20 +/- 6 mmHg) that were accompanied by vasoconstriction in all three
      beds. These data suggest that vestibular inputs lead to a complex pattern of
      cardiovascular changes that is distinct from that which occurs in response to
      activation of other types of somatic afferents.

PMID- 10896873
TI  - Hindbrain serotonin and the rapid induction of sodium appetite.
AB  - Both systemically administered furosemide and isoproterenol produce water intake
      (i.e., thirst). Curiously, however, in light of the endocrine and hemodynamic
      effects produced by these treatments, they are remarkably ineffective in
      eliciting intake of hypertonic saline solutions (i.e., operationally defined as
      sodium appetite). Recent work indicates that bilateral injections of the
      serotonin receptor antagonist methysergide into the lateral parabrachial nuclei
      (LPBN) markedly enhance a preexisting sodium appetite. The present studies
      establish that a de novo sodium appetite can be induced with LPBN-methysergide
      treatment under experimental conditions in which only water is typically
      ingested. The effects of bilateral LPBN injections of methysergide were studied
      on the intake of water and 0. 3 M NaCl following acute (beginning 1 h after
      treatment) diuretic (furosemide)-induced sodium and water depletion and following
      subcutaneous isoproterenol treatment. With vehicle injected into the LPBN,
      furosemide treatment and isoproterenol injection both caused water drinking but
      essentially no intake of hypertonic saline. In contrast, bilateral treatment of
      the LPBN with methysergide induced the intake of 0.3 M NaCl after subcutaneous
      furosemide and isoproterenol. Water intake induced by subcutaneous furosemide or
      isoproterenol was not changed by LPBN-methysergide injections. The results
      indicate that blockade of LPBN-serotonin receptors produces a marked intake of
      hypertonic NaCl (i.e., a de novo sodium appetite) after furosemide treatment as
      well as subcutaneous isoproterenol.

PMID- 10896874
TI  - Receptor subtypes mediating depressor responses to microinjections of nicotine
      into medial NTS of the rat.
AB  - Microinjections (50 nl) of nicotine (0.01-10 microM) into the nucleus of the
      solitary tract (NTS) of adult, urethan-anesthetized, artificially ventilated,
      male Wistar rats, elicited decreases in blood pressure and heart rate. Prior
      microinjections of alpha-bungarotoxin (alpha-BT) and alpha-conotoxin ImI
      (specific toxins for nicotinic receptors containing alpha7 subunits) elicited a
      20-38% reduction in nicotine responses. Similarly, prior microinjections of
      hexamethonium, mecamylamine, and alpha-conotoxin AuIB (specific blockers or toxin
      for nicotinic receptors containing alpha3beta4 subunits) elicited a 47-79%
      reduction in nicotine responses. Nicotine responses were completely blocked by
      prior sequential microinjections of alpha-BT and mecamylamine into the NTS.
      Complete blockade of excitatory amino acid receptors (EAARs) in the NTS did not
      attenuate the responses to nicotine. It was concluded that 1) the predominant
      type of nicotinic receptor in the NTS contains alpha3beta4 subunits, 2) a smaller
      proportion contains alpha7 subunits, 3) the presynaptic nicotinic receptors in
      the NTS do not contribute to nicotine-induced responses, and 4) EAARs in the NTS
      are not involved in mediating responses to nicotine.

PMID- 10896875
TI  - Electrical stimulation of afferent vagus nerve induces IL-1beta expression in the
      brain and activates HPA axis.
AB  - Possible roles of the afferent vagus nerve in regulation of interleukin (IL)
      1beta expression in the brain and hypothalamic-pituitary-adrenal (HPA) axis were
      examined in anesthetized rats. Levels of IL-1beta mRNA and protein in the brain
      were measured by comparative RT-PCR and ELISA. Direct electrical stimulation of
      the central end of the vagus nerve was performed continuously for 2 h. The
      afferent stimulation of the vagus nerve induced increases in the expression of
      mRNA and protein levels of IL-1beta in the hypothalamus and the hippocampus.
      Furthermore, expression of corticotropin-releasing factor mRNA was increased in
      the hypothalamus 2 h after vagal stimulation. Plasma levels of ACTH and
      corticosterone were also increased by this stimulation. The present results
      indicate that activation of the afferent vagus nerves itself can induce
      production of IL-1beta in the brain and activate the HPA axis. Therefore, the
      afferent vagus nerve may play an important role in transmitting peripheral
      signals to the brain in the infection and inflammation.

PMID- 10896876
TI  - Brain-blood permeability: TNF-alpha promotes escape of protein tracer from CSF to
      blood.
AB  - The objective of this study was to determine the effect of tumor necrosis factor
      (TNF)-alpha on the efflux of protein from the central nervous system to blood
      based on assessing the clearance of radiolabeled albumin from the cerebrospinal
      fluid (CSF) to blood in rats. (125)I-labeled human serum albumin ((125)I-HSA) was
      injected into a lateral ventricle, and venous blood was sampled hourly to
      determine the basal CSF protein clearance into the blood. After this, rats were
      intraventricularly infused with 10 microliter TNF-alpha and 10 microliter (131)I
      HSA (n = 6) or 10 microliter saline and 10 microliter (131)I-HSA (n = 6). Venous
      blood was sampled hourly for 3 h. (131)I-HSA tracer recovery increased threefold
      in the venous blood and was significantly higher in the spleen, muscles, and skin
      in animals treated with TNF-alpha. No significant changes were observed in
      control animals treated with saline. The data suggest that TNF-alpha promotes the
      clearance of protein macromolecules from the CSF to the venous blood.

PMID- 10896878
TI  - Effect of acute hypoxia on vasopressin release and intravascular fluid during
      dynamic exercise in humans.
AB  - To test the hypothesis that acute hypoxia does not modify the relationship
      between plasma vasopressin concentration ([AVP](p)) and plasma osmolality
      (P(osmol)) during exercise and that the increase in [AVP](p) during exercise is
      due mainly to the exercise intensity-dependent increase in P(osmol), we examined
      [AVP](p) during a graded exercise in a hypoxic condition (13% O(2), N(2) balance)
      in seven healthy male subjects. A graded exercise in a normoxic condition on a
      separate day served as the control. Hypoxia reduced peak aerobic power (VO(2
      peak)) by 32.4 +/- 2.7%. Blood samples obtained during rest and at around 25, 45,
      65, 80, and 100% of VO(2 peak) of each of the respective conditions were used for
      analyses of intravascular water and electrolyte balance. The pattern of the
      changes in fluid and electrolyte balance in response to percent VO(2 peak) was
      similar between the two conditions. Plasma volume decreased linearly as percent
      VO(2 peak) increased while P(osmol) increased in a curvilinear fashion with a
      steep increase occurring at above approximately 66% VO(2 peak). Above this
      relative exercise intensity, plasma sodium, potassium, and lactate concentrations
      also increased, whereas plasma bicarbonate concentration decreased. Thus
      transvascular fluid movement at above approximately 66% VO(2 peak) was due to the
      net efflux of hypotonic fluid out of the vascular space in both conditions. The
      relationship between [AVP](p) and P(osmol) during exercise in response to
      relative exercise intensity was similar between the two conditions. The results
      indicate that acute mild hypoxia itself has no direct effect on vasopressin
      release, and it does not modify the relationship between [AVP](p) and P(osmol)
      during exercise. The results also support the hypothesis that exercise-induced
      vasopressin release is primarily stimulated by increased P(osmol) produced by
      hypotonic fluid movement out of the vascular space in a relative exercise
      intensity-dependent manner.

PMID- 10896877
TI  - Enhanced sarcoplasmic reticulum Ca(2+) release following intermittent sprint
      training.
AB  - To evaluate the effect of intermittent sprint training on sarcoplasmic reticulum
      (SR) function, nine young men performed a 5 wk high-intensity intermittent
      bicycle training, and six served as controls. SR function was evaluated from
      resting vastus lateralis muscle biopsies, before and after the training period.
      Intermittent sprint performance (ten 8-s all-out periods alternating with 32-s
      recovery) was enhanced 12% (P < 0.01) after training. The 5-wk sprint training
      induced a significantly higher (P < 0.05) peak rate of AgNO(3)-stimulated Ca(2+)
      release from 709 (range 560-877; before) to 774 (596-977) arbitrary units Ca(2+).
      g protein(-1). min(-1) (after). The relative SR density of functional ryanodine
      receptors (RyR) remained unchanged after training; there was, however, a 48% (P <
      0.05) increase in total number of RyR. No significant differences in Ca(2+)
      uptake rate and Ca(2+)-ATPase capacity were observed following the training,
      despite that the relative density of Ca(2+)-ATPase isoforms SERCA1 and SERCA2 had
      increased 41% and 55%, respectively (P < 0.05). These data suggest that high
      intensity training induces an enhanced peak SR Ca(2+) release, due to an enhanced
      total volume of SR, whereas SR Ca(2+) sequestration function is not altered.

PMID- 10896879
TI  - Effects of photoperiod reduction on rat circadian rhythms of BP, heart rate, and
      locomotor activity.
AB  - The effects of a photoperiod reduction in the entrainment of circadian rhythms of
      systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR),
      and spontaneous locomotor activity (SLA) were determined in conscious Wistar rats
      by using radiotelemetry. Two groups of seven rats were maintained in a 12:12-h
      light-dark (12L/12D) photoperiod for 11 wk and then placed in a reduced
      photoperiod of 8:16-h light-dark (8L/16D) by advancing a 4-h darkness or by
      advancing and delaying a 2-h darkness for 6 wk. Finally, they were resynchronized
      to 12L/12D. Advancing a 4-h dark phase induced a 1-h advance of acrophase for
      SBP, DBP, and HR, but not for SLA. The percent rhythm, amplitude, and the 12-h
      mean values of all parameters were significantly decreased by the photoperiod
      reduction. When symmetrically advancing and delaying a 2-h dark phase, a 1 h 20
      min delay of acrophases and a decrease in percent rhythms and amplitudes of SBP,
      DBP, HR, and SLA were observed. Only the 12-h mean values of HR and SLA were
      decreased. Our findings show that the cardiovascular parameters differ from SLA
      in phase-shift response to photoperiod reduction and that the adjustment of
      circadian rhythms to change from 12L/12D to 8L/16D photoperiod depends on the
      direction of the extension of the dark period.

PMID- 10896880
TI  - Regulation of myogenin protein expression in denervated muscles from young and
      old rats.
AB  - Myogenin is a muscle-specific transcription factor participating in denervation
      induced increases in nicotinic ACh receptor (nAChR) gene expression. Although
      myogenin RNA expression in denervated muscle is well documented, surprisingly
      little is known about myogenin protein expression. Therefore, we assayed myogenin
      protein and RNA in innervated and denervated muscles from young (4 mo) and old
      (24-32 mo) rats and compared this expression to that of the nAChR alpha-subunit
      RNA. These assays revealed increased myogenin protein expression within 1 day of
      denervation, preceding detectable increases in nAChR RNA. By 3 days of
      denervation, myogenin and nAChR alpha-subunit RNA were increased 500- and 130
      fold, respectively, whereas myogenin protein increased 14-fold. Interestingly,
      old rats (32 mo) had 6-fold higher myogenin protein and approximately 80-fold
      higher mRNA levels than young rats. However, after denervation, expression levels
      were similar for young and old animals. The increased myogenin expression during
      aging, which tends to localize to small fibers, likely reflects spontaneous
      denervation and/or regeneration. Our results show that increased myogenin protein
      in denervated muscles correlates with the upregulation of its mRNA.

PMID- 10896881
TI  - Interaction between CCK and a preload on reduction of food intake is mediated by
      CCK-A receptors in humans.
AB  - Cholecystokinin (CCK) interacts with neural signals to induce satiety in several
      species, but the mechanisms are unclear. We therefore tested the hypothesis that
      alimentary CCK (CCK-A) receptors mediate the interaction of CCK with an appetizer
      on food intake in humans. CCK octapeptide (CCK-8, 0.75 microgram infused over 10
      min) or saline (placebo) with concomitant infusions of saline (placebo) or
      loxiglumide, a specific CCK-A antagonist, was infused into 16 healthy men with
      use of a double-blind, four-period design. All subjects received a standard 400
      ml appetizer (amounting to 154 kcal) but were free to eat and drink thereafter as
      much as they wished. The effect of these infusions on feelings of hunger and
      satiety and on food intake was quantified. CCK-8 induced a reduction in calorie
      intake (P < 0.05) compared with saline. Furthermore, a decrease in hunger
      feelings (P < 0.05, saline-CCK-8 vs. all other treatments) and an increase in
      fullness were observed. These effects were antagonized for hunger and fullness by
      loxiglumide. We conclude that CCK-8 interacts with an appetizer to modulate
      satiety in humans. These effects are mediated by CCK-A receptors.

PMID- 10896882
TI  - Role of adenosine in the hypoxia-induced hypothermia of toads.
AB  - The concept that hypoxia elicits a drop in body temperature (T(b)) in a wide
      variety of animals is not new, but the mechanisms remain unclear. We tested the
      hypothesis that adenosine mediates hypoxia-induced hypothermia in toads.
      Measurements of selected T(b) were performed using a thermal gradient. Animals
      were injected (into the lymph sac or intracerebroventricularly) with
      aminophylline (an adenosine receptor antagonist) followed by an 11-h period of
      hypoxia (7% O(2)) or normoxia exposure. Control animals received saline
      injections. Hypoxia elicited a drop in T(b) from 24.8 +/- 0.3 to 19. 5 +/- 1.1
      degrees C (P < 0.05). Systemically applied aminophylline (25 mg/kg) did not
      change T(b) during normoxia, indicating that adenosine does not alter normal
      thermoregulatory function. However, aminophylline (25 mg/kg) significantly
      blunted hypoxia-induced hypothermia (P < 0.05). To assess the role of central
      thermoregulatory mechanisms, a smaller dose of aminophylline (0.25 mg/kg), which
      did not alter hypoxia-induced hypothermia systemically, was injected into the
      fourth cerebral ventricle. Intracerebroventricular injection of aminophylline
      (0.25 mg/kg) caused no significant change in T(b) under normoxia, but it
      abolished hypoxia-induced hypothermia. The present data indicate that adenosine
      is a central and possibly peripheral mediator of hypoxia-induced hypothermia.

PMID- 10896883
TI  - Regional regulation of choroidal blood flow by autonomic innervation in the rat.
AB  - Regional influences of parasympathetic and sympathetic innervation on choroidal
      blood flow were investigated in anesthetized rats. Parasympathetic
      pterygopalatine neurons were activated by electrically stimulating the superior
      salivatory nucleus, whereas sympathetic neurons were activated by cervical
      sympathetic trunk stimulation and uveal blood flow was measured by laser Doppler
      flowmetry. Parasympathetic stimulation increased flux in the anterior choroid and
      nasal vortex veins but not in the posterior choroid. Vasodilation was blocked
      completely by the neuronal nitric oxide synthase inhibitor 1-(2
      trifluoromethylphenyl)imidazole but was unaffected by atropine. Sympathetic
      stimulation decreased flux in all regions, and this was blocked by prazosin.
      Parasympathetic stimulation did not affect vasoconstrictor responses to
      sympathetic stimulation in the posterior choroid but attenuated the decrease in
      blood flow through the anterior choroid and vortex veins via a nitrergic
      mechanism. We conclude that sympathetic alpha-noradrenergic vasoconstriction
      occurs throughout the choroid, whereas parasympathetic nitrergic vasodilation
      plays a selective role in modulating blood flow in anterior tissues of the eye.

PMID- 10896884
TI  - Differential pattern of spinal sympathetic outflow in response to stimulation of
      the caudal medullary raphe.
AB  - In urethan-anesthetized cats, frequency domain analysis was used to explore the
      mechanisms of differential responses of inferior cardiac (CN), vertebral (VN),
      and renal (RN) sympathetic nerves to electrical stimulation of a discrete region
      of the medullary raphe (0-2 mm caudal to the obex). Raphe stimulation in
      baroreceptor-denervated cats at frequencies (7-12 Hz) that entrained the 10-Hz
      rhythm in nerve activity decreased CN and RN activities but increased VN
      activity. The reductions in CN and RN discharges were associated with decreased
      low-frequency (</=6 Hz) power and either increased (low stimulus intensity) or
      decreased (high stimulus intensity) 10-Hz band power. In contrast, VN 10-Hz band
      power was increased at all stimulus intensities, without changes in low-frequency
      power. High-frequency (25 Hz) stimulation decreased low-frequency activity of CN
      and RN discharges in both baroreceptor-denervated and baroreceptor-intact cats,
      without decreasing VN low-frequency activity. We propose that the differential
      pattern produced by raphe stimulation involves resonance at the level of the 10
      Hz oscillators and differential inhibition of follower circuits that transmit
      both 10-Hz and low-frequency activity to sympathetic nerves.

PMID- 10896885
TI  - Expression of a duplicate Na,K-ATPase beta(1)-isoform in the European eel
      (Anguilla anguilla).
AB  - Recent studies on teleost fish have suggested that their genomes have undergone
      ancient polyploidization events resulting in the duplication of the genome. A
      duplicate copy of the Na,K-ATPase beta(1)-isoform (called beta(233)) has been
      identified in the European eel (Anguilla anguilla). The beta(233)-isoform shares
      high levels of nucleotide (74.8%) and amino acid (69.9%) homology with the eel
      beta(1)-subunit as well as other vertebrate beta(1)-sequences. Compared with the
      widely expressed beta(1)-isoform, expression of beta(233)-mRNA is mainly
      restricted to epithelial tissues. Seawater acclimation induced increases in
      beta(233)-mRNA levels in kidney, gill, and intestine of migratory "silver" but
      not the nonmigratory "yellow" adult eels, suggesting that the factors responsible
      for this upregulation are themselves developmentally regulated. Expression of a
      variably glycosylated 40- to 52-kDa beta(233)-protein in both gill "chloride" and
      intestinal epithelial cells suggests that the beta(233)-isoform of Na,K-ATPase
      may play an important functional role in the major osmoregulatory tissues of
      euryhaline fish such as the eel.

PMID- 10896886
TI  - Attenuation of circadian rhythms of food intake and respiration in aging diabetes
      prone BHE/Cdb rats.
AB  - The hypothesis that BHE/Cdb rats with mutations in their mitochondrial genome
      might accommodate this mutation by changing their food intake patterns was
      tested. Four experiments were conducted. Experiments 1 and 2 examined food intake
      patterns of BHE/Cdb rats fed a stock diet or BHE/Cdb and Sprague-Dawley rats fed
      a high-fat diet from weaning. Experiment 3 examined the daily rhythms of
      respiration and heat production in these rats at 200 days of age. Experiment 4
      examined the effects of diet composition on these measurements at 50-day
      intervals. The Sprague-Dawley rats, regardless of diet, had the typical day-night
      rhythms of feeding and respiration. In contrast, the BHE/Cdb rats fed the high
      fat diet showed normal rhythms initially, but with age, these rhythms were
      attenuated. The changes in rhythms preceded the development of glucose
      intolerance.

PMID- 10896887
TI  - Nucleus of the solitary tract lesions enhance drinking, but not vasopressin
      release, induced by angiotensin.
AB  - Rats with chronic nucleus of the solitary tract lesions (NTS-X) drink water and
      release vasopressin (VP) in response to reduced blood volume despite an absence
      of neural signals from cardiac and arterial baroreceptors. The present study
      determined whether rats with NTS-X have a greater sensitivity to circulating ANG
      II, which may contribute to the drinking and VP responses to hypovolemia. In
      conscious control rats and rats with NTS-X, ANG II was infused intravenously for
      1 h at 10, 100, or 250 ng. kg(-1). min(-1). At the two higher doses, ANG II
      stimulated more water intake with a shorter latency to drink in rats with NTS-X
      than in control rats. In contrast, infusion of ANG II produced comparable
      increases in plasma VP in the two groups. At the two higher doses, ANG II
      produced an enhanced increase in arterial pressure (AP) in rats with NTS-X, and
      the bradycardia seen in control rats was reversed to a tachycardia. Infusion of
      hypertonic saline, which did not alter AP or heart rate, produced comparable
      drinking and VP release in the two groups. These results demonstrate that chronic
      NTS-X increases the dipsogenic response of rats to systemic ANG II but has no
      effect on ANG II-induced VP release or the osmotic stimulation of these
      responses.

PMID- 10896888
TI  - Postprandial metabolism and aversive response in rats fed a threonine-devoid
      diet.
AB  - Lack of an indispensable amino acid in the diet induces a rapid reduction in food
      intake. In this study, we assessed whether the anorectic signal after ingestion
      of a meal lacking threonine originated from either direct perception of the
      decrease in plasma threonine or from an indirect effect related to increased
      postprandial amino acid catabolism and energy expenditure. We observed that 3 g
      of such a meal was sufficient to induce an aversive response to the diet within 2
      h. Postprandial changes to plasma ammonia and urea, urinary urea, and energy
      metabolism did not differ from those measured after a control meal. In contrast,
      plasma threonine levels fell within 1 h after the meal. It is concluded that an
      increase in postprandial energy expenditure is not involved in the anorectic
      response to eating a threonine-devoid diet. The drop in plasma threonine levels
      may be a potential signal, but the fact that the decrease in food intake occurred
      1 h after the decrease in plasma threonine questions a direct causal
      relationship.

PMID- 10896889
TI  - Effects of ambient temperature on metabolic rate, respiratory quotient, and
      torpor in an arctic hibernator.
AB  - Arctic ground squirrels (Spermophilus parryii) overwinter in hibernaculum
      conditions that are substantially below freezing. During torpor, captive arctic
      ground squirrels displayed ambient temperature (T(a))-dependent patterns of core
      body temperature (T(b)), metabolic rate (TMR), and metabolic fuel use, as
      determined by respiratory quotient (RQ). At T(a) 0 to -16 degrees C, T(b)
      remained relatively constant, and TMR rose proportionally with the expanding
      gradient between T(b) and T(a), increasing >15-fold from a minimum of 0.0115 +/-
      0.0012 ml O(2). g(-1). h(-1). At T(a) 0-20 degrees C, T(b) increased with T(a);
      however, TMR did not change significantly from T(b) 0 to 12 degrees C, indicating
      temperature-independent inhibition of metabolic rate. The overall change in TMR
      from T(b) 4 to 20 degrees equates to a Q(10) of 2.4, but within this range of
      T(b), Q(10) changed from 1.0 to 14.1. During steady-state torpor at T(a) 4 and 8
      degrees C, RQ averaged 0.70 +/- 0.013, indicating exclusive lipid catabolism. At
      T(a) -16 and 20 degrees C, RQ increased significantly to >0.85, consistent with
      recruitment of nonlipid fuels. RQ was negatively correlated with maximum torpor
      bout length. For T(a) values <0 degrees C, this relationship supports the
      hypothesis that availability of nonlipid metabolic fuels limits torpor duration
      in hibernating mammals; for T(a) values >0 degrees C, hypotheses linked to body
      temperature are supported. Because anterior body temperatures differ from core,
      overall, the duration torpor can be extended in hibernating mammals may be
      dependent on brain temperature.

PMID- 10896890
TI  - Effect of renal denervation on renin gene expression, concentration, and
      secretion in mature ovine fetus.
AB  - To determine the role of the renal nerves on renin secretion and expression in
      the mature ovine fetus, we performed bilateral renal denervation on eight fetuses
      of time-dated pregnant ewes (126.8 +/- 0.6 days gestation) and compared renin in
      them to seven fetuses that underwent sham denervation (126.7 +/- 0.6 days
      gestation). Fetal arterial and venous catheters were implanted, and after 5-7
      days of recovery isoproterenol was infused. Plasma active renin was lower in
      denervated animals than in intact animals under basal conditions and at each dose
      of isoproterenol. Plasma prorenin levels were lower in denervated fetuses but
      unaffected by isoproterenol. Denervation did not change renal renin, prorenin, or
      renin mRNA, but it did block isoproterenol-induced increases in renin mRNA in
      renocortical cells in vitro. We conclude that the renal nerves are required for
      renin secretory mechanisms and responsiveness of renin mRNA to beta-adrenergic
      stimulation but not for the expression of renin in the fetal kidney. We propose
      that one or more of the factors that maintain renin expression in the perinatal
      period may be absent or may be replaced by the renal nerves in the adult.

PMID- 10896891
TI  - Octreotide-induced drinking, vasopressin, and pressure responses: role of central
      angiotensin and ACh.
AB  - The involvement of central angiotensinergic and cholinergic mechanisms in the
      effects of the intracerebroventricularly injected somatostatin analog octreotide
      (Oct) on drinking, blood pressure, and vasopressin secretion in the rat was
      investigated. Intracerebroventricular Oct elicited prompt drinking lasting for 10
      min. Water consumption depended on the dose of Oct (0.01, 0.1, and 0. 4
      microgram). The drinking response to Oct was inhibited by pretreatments with the
      intracerebroventricularly injected angiotensin-converting enzyme inhibitor
      captopril, the AT(1)/AT(2) angiotensin receptor antagonist saralasin, the
      selective AT(1) receptor antagonist losartan, or the muscarinic cholinergic
      receptor antagonist atropine. The dipsogenic effect of Oct was not altered by
      prior subcutaneous injection of naloxone. Oct stimulated vasopressin secretion
      and enhanced blood pressure. These responses were also blocked by pretreatments
      with captopril or atropine. Previous reports indicate that the central
      angiotensinergic and cholinergic mechanisms stimulate drinking and vasopressin
      secretion independently. We suggest that somatostatin acting on sst2 or sst5
      receptors modulates central angiotensinergic and cholinergic mechanisms involved
      in the regulation of fluid balance.

PMID- 10896892
TI  - Tissue hypoxia inhibits prostaglandin and nitric oxide production and prevents
      ductus arteriosus reopening.
AB  - Regulation of ductus arteriosus (DA) tension depends on a balance between oxygen
      induced constriction and PG and nitric oxide (NO)-mediated relaxation. After
      birth, increasing Pa(O(2)) produces DA constriction. However, as the full-term
      ductus constricts, it develops severe tissue hypoxia in its inner vessel wall
      (oxygen concentration <0.2%). We used isolated rings of fetal lamb DA to
      determine why the constricted ductus does not relax and reopen as it becomes
      hypoxic. We used a modification of the 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3
      pentafluoropropyl) acetamide (EF5) technique (Clyman RI, Chan CY, Mauray F, Chen
      YQ, Cox W, Seidner SR, Lord EM, Weiss H, Wale N, Evan SM, and Koch CJ. Pediatr
      Res 45: 19-29, 1999) to determine mean tissue oxygen concentration. A decrease in
      the ductus' mean tissue oxygen concentration from 1.4 to 0.1% lowers the
      isometric tone of the ductus by 15 +/- 10% of its maximal active tension (the
      maximal tension that can be produced by the ductus). Although decreases in oxygen
      concentration diminish ductus tension, most of the vasoconstrictor tone in the
      ductus is independent of ambient oxygen concentration. This oxygen-independent
      tone is equivalent to 64 +/- 10% of the maximal active tension. At mean tissue
      oxygen concentrations >0.2%, endogenous PGs and NO inhibit more than 40% of the
      active tension developed by the ductus. However, when tissue oxygen
      concentrations drop below 0.2%, the constitutive relaxation of the ductus by
      endogenous PGs and NO is lost. In the absence of PG and NO production, tension
      increases to a level normally observed only after treatment of the ductus with
      indomethacin and nitro-L-arginine methyl ester (inhibitors of PG and NO
      production). Therefore, under conditions of severe hypoxia (tissue oxygen
      concentration <0.2% oxygen), the loss of PG- and NO-mediated relaxation more than
      compensates for the loss of oxygen-induced tension. We hypothesize that this
      increased ductus tone enables the vessel to remain closed as it undergoes tissue
      remodeling.

PMID- 10896893
TI  - Na(+)-K(+)-ATPase is distributed to microvillous and basal membrane of the
      syncytiotrophoblast in human placenta.
AB  - Despite its importance for placental function, syncytiotrophoblast Na(+)-K(+)
      ATPase has not been studied in detail. We purified syncytiotrophoblast
      microvillous (MVM) and basal (BM) membranes from full-term human placenta.
      Western blotting with isoform-specific antibodies demonstrated the presence of
      the alpha(1)-subunit, but not the alpha(2)- or alpha(3)-subunits, in MVM and BM.
      Relative density per unit membrane protein in BM was 48 +/- 1% (mean +/- SE, n =
      4, P < 0.02) of that in the MVM. The activity of Na(+)-K(+)-ATPase was lower in
      BM (1.4 +/- 0.14 micromol. mg(-1). min(-1), n = 8, P < 0.02) than in MVM (3.9 +/-
      0.25 micromol. mg(-1). min(-1)). Immunocytochemistry confirmed the distribution
      of Na(+)-K(+)-ATPase to MVM and BM. These findings suggest that the
      syncytiotrophoblast represents a type of transporting epithelium different from
      the classical epithelia found in the small intestine and kidney, where Na(+)-K(+)
      ATPase is confined to the basolateral membrane only. This unique polarization of
      the Na(+) pump does not, however, preclude a net transcellular transport of Na(+)
      to the fetus.

PMID- 10896894
TI  - Increased expression of spinal cord Fos protein induced by bladder stimulation
      after spinal cord injury.
AB  - These studies examined Fos protein expression in spinal cord neurons synaptically
      activated by stimulation of bladder afferent pathways after spinal cord injury
      (SCI). In urethan-anesthetized Wistar rats after SCI for 6 wk, intravesical
      saline distension significantly (P </= 0.005) increased the number of Fos
      immunoreactive (IR) cells in the rostrolumbar (L1, 38 cells/section; L2, 29
      cells/section) and caudal lumbosacral (L6, 140 cells/section; S1, 110
      cells/section) spinal cord compared with control animals, but Fos expression in
      the L5 segment was not altered. The distribution of Fos-IR cells was also altered
      in the lumbosacral spinal cord. Significantly greater numbers of Fos-IR cells
      were distributed in the dorsal commissure and medial and lateral dorsal horn
      after intravesical distension in SCI animals. Large percentages of
      parasympathetic (75%) and sympathetic (85%) preganglionic neurons also expressed
      Fos-IR after intravesical distension in SCI animals. These results demonstrate
      that bladder distension produces increased numbers and an altered distribution
      pattern of Fos-IR cells after SCI. This pattern resembles that after noxious
      irritation of the bladder in control animals. Pretreatment with capsaicin
      significantly reduced the number of Fos-IR cells induced by bladder distension
      after SCI. These data suggest that SCI can reveal an altered Fos expression
      pattern in response to a nonnoxious bladder stimulus that is partially mediated
      by capsaicin-sensitive bladder afferents.

PMID- 10896895
TI  - Role of the locus ceruleus in baroreceptor regulation of supraoptic vasopressin
      neurons in the rat.
AB  - The goal of this study was to identify the source of baroreceptor-related
      noradrenergic innervation of the diagonal band of Broca (DBB). Male Sprague
      Dawley rats underwent sinoaortic denervation (SAD, n = 13) or sham SAD surgery (n
      = 13). We examined Fos expression produced by baroreceptor activation and
      dopamine-beta-hydroxylase immunofluorescence in hindbrain regions that contain
      noradrenergic neurons. Baroreceptors were stimulated by increasing blood pressure
      >40 mmHg with phenylephrine (10 microgram. kg(-1). min(-1) iv) in sham SAD and
      SAD rats. Controls were infused with 0.9% saline. Only the locus ceruleus (LC)
      demonstrated a baroreceptor-dependent increase in Fos immunoreactivity in
      dopamine-beta-hydroxylase-positive neurons. In a second experiment, normal rats
      received rhodamine-labeled microsphere injections in the DBB (n = 12) before
      phenylephrine or vehicle infusion. In these experiments, only the LC consistently
      contained Fos-positive cells after phenylephrine infusion that were retrogradely
      labeled from the DBB. Finally, we lesioned the LC with ibotenic acid and obtained
      extracellular recordings from identified vasopressin neurons in the supraoptic
      nucleus. LC lesions significantly reduced the number of vasopressin neurons that
      were inhibited by acute baroreceptor stimulation. Together, these results suggest
      that noradrenergic neurons in the LC participate in the baroreflex activation of
      the DBB and may thus be important in the baroreflex inhibition of vasopressin
      releasing neurons in the supraoptic nucleus.

PMID- 10896896
TI  - Spinal GABA(A) receptors do not mediate the sympathetic baroreceptor reflex in
      the rat.
AB  - Activation of baroreceptors causes efferent sympathetic nerve activity (SNA) to
      fall. Two mechanisms could account for this sympathoinhibition: disfacilitation
      of sympathetic preganglionic neurons (SPN) and/or direct inhibition of SPN. The
      roles that spinal GABA and glycine receptors play in the baroreceptor reflex were
      examined in anesthetized, paralyzed, and artificially ventilated rats. Spinal
      GABA(A) receptors were blocked by an intrathecal injection of bicuculline
      methiodide, whereas glycine receptors were blocked with strychnine. Baroreceptors
      were activated by stimulation of the aortic depressor nerve (ADN), and a
      somatosympathetic reflex was used as control. After an intrathecal injection of
      vehicle, there was no effect on any measured variable or evoked reflex. In
      contrast, bicuculline caused a dose-dependent increase in arterial pressure, SNA,
      phrenic nerve discharge, and it significantly facilitated the somatosympathetic
      reflex. However, bicuculline did not attenuate either the depressor response or
      sympathoinhibition evoked after ADN stimulation. Similarly, strychnine did not
      affect the baroreceptor-induced depressor response. Thus GABA(A) and glycine
      receptors in the spinal cord have no significant role in baroreceptor-mediated
      sympathoinhibition.

PMID- 10896897
TI  - Nifedipine-induced inhibition of parasympathetic-mediated vasodilation in the
      orofacial areas of the cat.
AB  - In anesthetized cats, we 1) compared the effects of antihypertensive agents
      (nifedipine, clonidine, phentolamine, propranolol, and nitroprusside) on the
      parasympathetic vasodilations elicited by lingual nerve (LN) stimulation in the
      lower lip and tongue and 2) investigated the mechanisms underlying the inhibitory
      effect of nifedipine on parasympathetic lower lip vasodilation. At the doses
      used, each antihypertensive agent reduced systemic arterial blood pressure by
      approximately 20 mmHg; however, the parasympathetic vasodilation elicited by LN
      stimulation was significantly reduced only by nifedipine. This inhibitory effect
      of nifedipine was not seen when LN was stimulated during ongoing repetitive
      stimulation of the superior cervical sympathetic trunk at 1-Hz frequency. This
      suggests that the ability of lip and tongue blood vessels to relax to
      parasympathetic stimulation is not directly impaired by this calcium channel
      blocker and that the inhibitory effects of nifedipine seen here probably resulted
      from an action on postsynaptic sites in vascular smooth muscle that caused a
      reduction in preexisting sympathetic vasoconstrictor tone (by inhibiting calcium
      influx into the vascular smooth muscle cell).

PMID- 10896898
TI  - Effect of maternal undernutrition in early gestation on ovine fetal blood
      pressure and cardiovascular reflexes.
AB  - Human epidemiological and animal experimental studies suggest that maternal
      undernutrition during pregnancy may alter cardiovascular development of the
      offspring. The extent to which these effects involve changes in fetal
      cardiovascular function and whether they are necessarily linked to reduced fetal
      growth is unknown. In sheep, we investigated the effect of a 15% reduction in
      maternal global nutrition for the first 70 days of gestation (term = 147 days) on
      fetal blood pressure development, baroreflex control of fetal heart rate (FHR),
      and cardiovascular responses to acute hypoxemia in late gestation. Basal mean
      arterial pressure (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood
      pressure (P < 0.05), and rate-pressure product (P < 0.001) were significantly
      lower in fetuses of nutritionally restricted ewes (R) compared with controls (C).
      FHR was not altered. The operating point for the fetal baroreflex was
      significantly lower in R fetuses compared with C (P < 0.01), but there was no
      difference between the groups in the cardiovascular response to hypoxemia. We
      conclude that mild maternal undernutrition alters fetal cardiovascular
      development, producing low blood pressure and resetting of baroreflex control
      mechanisms. This effect occurs without any changes in fetal growth or blood gas
      status.

PMID- 10896899
TI  - Age-related thermoregulatory differences during core cooling in humans.
AB  - The current study assessed sympathetic neuronal and vasomotor responses, total
      body oxygen consumption, and sensory thermal perception to identify
      thermoregulatory differences in younger and older human subjects during core
      cooling. Cold fluid (40 ml/kg, 4 degrees C) was given intravenously over 30 min
      to decrease core temperature (Tc) in eight younger (age 18-23) and eight older
      (age 55-71) individuals. Compared with younger subjects, the older subjects had
      significantly lower Tc thresholds for vasoconstriction (35.5 +/- 0.3 vs. 36.2 +/-
      0.2 degrees C, P = 0.03), heat production (35.2 +/- 0.4 vs. 35.9 +/- 0.1 degrees
      C, P = 0.04), and plasma norepinephrine (NE) responses (35.0 vs. 36.0 degrees C,
      P < 0.05). Despite a lower Tc nadir during cooling, the maximum intensities of
      the vasoconstriction (P = 0.03) and heat production (P = 0.006) responses were
      less in the older compared with the younger subjects, whereas subjective thermal
      comfort scores were similar. Plasma NE concentrations increased fourfold in the
      younger but only twofold in the older subjects at maximal Tc cooling. The
      vasomotor response for a given change in plasma NE concentration was decreased in
      the older group (P = 0.01). In summary, aging is associated with 1) a decreased
      Tc threshold and maximum response intensity for vasoconstriction, total body
      oxygen consumption, and NE release, 2) decreased vasomotor responsiveness to NE,
      and 3) decreased subjective sensory thermal perception.

PMID- 10896901
TI  - Microbe-host interactions in the alimentary tract: the gateway to understanding
      inflammatory bowel disease.

PMID- 10896900
TI  - The science, economics, and effectiveness of combination therapy for hepatitis C.

PMID- 10896902
TI  - Effect of growth hormone and glutamine on the short bowel: five years later.

PMID- 10896903
TI  - Screening and shouting about HCV.

PMID- 10896904
TI  - Improving prognosis in hepatorenal syndrome.

PMID- 10896905
TI  - The stomach talks with the pituitary.

PMID- 10896906
TI  - The role of polyamines in gastric mucus synthesis inhibited by cigarette smoke or
      its extract.
AB  - BACKGROUND: Cigarette smoking was shown to delay gastric ulcer healing and reduce
      synthesis of mucus, which is important for gastric ulcer protection and healing.
      Polyamines are important in these processes. AIMS: To study the effects of
      cigarette smoking on the synthesis of mucus and to investigate if such an effect
      is acting by interference with the polyamine pathway. METHODS: Gastric mucosal
      ornithine decarboxylase activity, mucous secreting layer thickness, and ulcer
      size were determined after different concentrations of cigarette smoke exposure
      (0, 2, or 4%) in intact animals and animals with ulcers. Synthesis of mucus and
      ornithine decarboxylase activity and mRNA expression were also assessed in
      cigarette smoke extract treated MKN-28 cells. RESULTS: Exposure to cigarette
      smoke significantly reduced the thickness of the mucous secreting layer and
      gastric mucosal ornithine decarboxylase activity in animals with or without
      ulcers. Spermidine not only reversed inhibition of mucus synthesis in both intact
      and ulcer bearing animals but also reversed the delay in ulcer healing. Cigarette
      smoke extract significantly reduced mucus synthesis and ornithine decarboxylase
      activity but not its mRNA expression in MKN-28 cells. The reduction in mucus
      synthesis was restored by spermidine. CONCLUSIONS: Cigarette smoke and its
      extract repress mucus synthesis in vivo and in vitro, respectively. Reduction of
      ornithine decarboxylase activity in gastric mucosa is closely associated with
      this effect.

PMID- 10896907
TI  - Leptin secretion and leptin receptor in the human stomach.
AB  - BACKGROUND AND AIM: The circulating peptide leptin produced by fat cells acts on
      central receptors to control food intake and body weight homeostasis. Contrary to
      initial reports, leptin expression has also been detected in the human placenta,
      muscles, and recently, in rat gastric chief cells. Here we investigate the
      possible presence of leptin and leptin receptor in the human stomach. METHODS:
      Leptin and leptin receptor expression were assessed by immunohistochemistry,
      reverse transcriptase-polymerase chain reaction (RT-PCR), and western blot
      analysis on biopsy samples from 24 normal individuals. Fourteen (10 healthy
      volunteers and four patients with non-ulcer dyspepsia and normal gastric mucosa
      histology) were analysed for gastric secretions. Plasma and fundic mucosa leptin
      content was determined by radioimmunoassay. RESULTS: In fundic biopsies from
      normal individuals, immunoreactive leptin cells were found in the lower half of
      the fundic glands. mRNA encoding ob protein was detected in the corpus of the
      human stomach. The amount of fundic leptin was 10.4 (3.7) ng leptin/g mucosa, as
      determined by radioimmunoassay. Intravenous infusions of pentagastrin or secretin
      caused an increase in circulating leptin levels and leptin release into the
      gastric juice. The leptin receptor was present in the basolateral membranes of
      fundic and antral gastric cells. mRNA encoding Ob-RL was detected in both the
      corpus and antrum, consistent with a protein of approximately 120 kDa detected by
      immunoblotting. CONCLUSION: These data provide the first evidence of the presence
      of leptin and leptin receptor proteins in the human stomach and suggest that
      gastric epithelial cells may be direct targets for leptin. Therefore, we conclude
      that leptin may have a physiological role in the human stomach, although much
      work is required to establish this.

PMID- 10896908
TI  - Effect of proinflammatory interleukins on jejunal nutrient transport.
AB  - AIM: We examined the effect of proinflammatory and anti-inflammatory interleukins
      on jejunal nutrient transport and expression of the sodium-glucose linked
      cotransporter (SGLT-1). METHODS: 3-O-methyl glucose and L-proline transport rates
      were examined in New Zealand White rabbit stripped, short circuited jejunal
      tissue. The effects of the proinflammatory cytokines interleukin (IL)-1alpha, IL
      6, and IL-8, IL-1alpha plus the specific IL-1 antagonist, IL-1ra, and the anti
      inflammatory cytokine IL-10 were investigated. In separate experiments, passive
      tissue permeability was assessed and brush border SGLT-1 expression was measured
      by western blot in tissues exposed to proinflammatory interleukins. RESULTS: The
      proinflammatory interleukins IL-6, IL-1alpha, and IL-8 significantly increased
      glucose absorption compared with control levels. This increase in glucose
      absorption was due to an increase in mucosal to serosal flux. IL-1alpha and IL-8
      also significantly increased L-proline absorption due to an increase in
      absorptive flux. The anti-inflammatory IL-10 had no effect on glucose transport.
      The receptor antagonist IL-1ra blocked the ability of IL-1alpha to stimulate
      glucose transport. IL-8 had no effect on passive tissue permeability. SGLT-1
      content did not differ in brush border membrane vesicles (BBMV) from control or
      interleukin treated tissue. CONCLUSIONS: These findings suggest that intestinal
      inflammation and release of inflammatory mediators such as interleukins increase
      nutrient absorption in the gut. The increase in glucose transport does not appear
      to be due to changes in BBMV SGLT-1 content.

PMID- 10896909
TI  - Cytokine gene expression during postnatal small intestinal development:
      regulation by glucocorticoids.
AB  - BACKGROUND: In the intestinal mucosa, numerous cytokines produced by the
      epithelium, fibroblasts, and immune cells were shown to affect epithelial
      differentiation and proliferation through epithelial-mesenchymal and epithelial
      immune cell interactions. To date, the importance of cytokines in postnatal
      development of the rat small intestine has not been established. AIM: To
      investigate the developmental changes in expression of mucosal cytokines in the
      postnatal maturation of the rat small intestinal epithelium and their regulation
      by glucocorticoids (GC). METHODS: Mucosal maturation was assessed by the onset of
      sucrase-isomaltase (SI) mRNA, analysed by in situ hybridisation. The amount of
      transforming growth factor beta1 (TGF-beta1), beta2 (TGF-beta2), tumour necrosis
      factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and TGF-alpha was
      analysed by reverse transcription-polymerase chain reaction (RT-PCR) in mucosal
      extracts from weaning (14-21 days old) and adult rats, or one day after an
      injection of hydrocortisone (HC) in 11 day old rats. Similarly, expression of
      cytokines and the regulatory effect of GC were studied on cultured subepithelial
      myofibroblasts cloned from postnatal jejunum and ileum cultured in the absence or
      presence of dexamethasone (DX). RESULTS: TGF-beta1, TGF-beta2, and IL-1beta
      decreased during the third week of life while levels of TNF-alpha increased and
      TGF-alpha remained constant. In parallel, SI transcripts increased and showed a
      progressive accumulation in the apical part of the enterocytes first localised at
      the base of the villi from 18 days onwards. Interestingly, precocious induction
      of SI mRNA by HC paralleled the decrease in expression of TGF-beta isoforms and
      of IL-1beta. All cytokines were expressed in the myofibroblast cell lines. In
      addition, the results showed that TNF-alpha was differentially expressed in basal
      culture conditions and after DX stimulation in jejunal and ileal myofibroblasts.
      DX decreased IL-1beta but not the TGF-beta isoforms, similar to that in vivo.
      CONCLUSIONS: This study shows that mucosal cytokines are developmentally
      regulated and that GC are potentially involved in this regulation in parallel
      with maturation of the gut mucosa at weaning.

PMID- 10896910
TI  - Effect of high dose growth hormone with glutamine and no change in diet on
      intestinal absorption in short bowel patients: a randomised, double blind,
      crossover, placebo controlled study.
AB  - BACKGROUND: High dose growth hormone, glutamine, and a high carbohydrate diet may
      improve intestinal function in short bowel patients. AIMS: To investigate if
      growth hormone with glutamine and no change in diet improved intestinal function.
      PATIENTS AND METHODS: Eight short bowel patients were randomised in a double
      blind crossover study between placebo and growth hormone (mean 0.12 mg/kg/day)
      with oral (mean 28 g/day) and parenteral glutamine (mean 5.2 g/day) for 28 days.
      Balance studies were performed at baseline and five days after placebo and
      treatment were terminated. Dietary energy, carbohydrate, and fat were maintained
      as usual. RESULTS: Growth hormone with glutamine did not improve intestinal
      absorption of energy (baseline, placebo, treatment, mean: 46%, 48%, 46% of oral
      intake, respectively), carbohydrate (71%, 70%, 71%), fat (20%, 15%, 18%),
      nitrogen (27%, 18%, 19%), wet weight (37%, 39%, 31%), sodium (-16%, -16%, -36%),
      potassium (43%, 47%, 33%), calcium (-16%, -16%, -15%) or magnesium (-3%, 4%, 2%)
      compared with placebo or baseline (p>0.05) five days after treatment was
      terminated. All patients experienced adverse effects. CONCLUSIONS: Combined high
      dose growth hormone and glutamine administered for four weeks did not improve
      intestinal absorption five days after treatment was terminated in short bowel
      patients on their usual diet.

PMID- 10896912
TI  - Vitamin D receptor gene polymorphism: association with Crohn's disease
      susceptibility.
AB  - BACKGROUND: The vitamin D receptor (VDR) gene represents a strong positional
      candidate susceptibility gene for inflammatory bowel disease (IBD). The VDR gene
      maps to a region on chromosome 12 that has been shown to be linked to IBD by
      genome screening techniques. It is the cellular receptor for 1,25(OH)(2) vitamin
      D(3) (calcitriol) which has a wide range of different regulatory effects on the
      immune system. IBD is characterised by activation of the mucosal immune system.
      AIM: To determine if polymorphisms in the VDR gene are associated with
      susceptibility to IBD SUBJECTS: European Caucasoids: 158 patients with ulcerative
      colitis, 245 with Crohn's disease, and 164 cadaveric renal allograft donor
      controls. METHOD: Single nucleotide polymorphisms (TaqI, ApaI, and FokI) in VDR
      were typed in patients with Crohn's disease, ulcerative colitis, and controls by
      polymerase chain reaction with sequence specific primers. RESULTS: There were
      significantly more homozygotes for the TaqI polymorphism at codon 352 of exon 8
      (genotype "tt") among patients with Crohn's disease (frequency 0.22) than
      patients with ulcerative colitis (0.12) or controls (0.12) (odds ratio 1.99; 95%
      confidence interval 1.14-3.47; p=0.017). CONCLUSION: This study provides
      preliminary evidence for a genetic association between Crohn's disease
      susceptibility and a gene that lies within one of the candidate regions
      determined by linkage analysis.

PMID- 10896911
TI  - Thiol methyltransferase activity in inflammatory bowel disease.
AB  - BACKGROUND: Luminal anionic sulphide may contribute to epithelial damage in
      ulcerative colitis. Thiol methyltransferase (TMT) governs sulphide detoxification
      by the colonic mucosa and circulating erythrocytes. AIMS: To measure levels of
      TMT activity in erythrocytes of surgically treated cases of colitis or in rectal
      biopsies of defined groups of colitis. PATIENTS: Venepuncture blood was obtained
      from 37 blood donors and 27 subjects who had previously undergone a
      proctocolectomy for colitis: 18 for ulcerative colitis and nine for Crohn's
      colitis. Rectal biopsies from 122 cases were obtained: 47 without mucosal
      disease, 33 post-colon resection for cancer, 14 with moderate to severe
      ulcerative colitis, 15 with quiescent ulcerative colitis, seven with acute
      Crohn's colitis, and six with radiation proctitis. METHODS: TMT activity was
      measured by high performance liquid chromatography with radioactive detection to
      measure (14)C methylmercaptoethanol formation, the reaction product of cell
      extracts incubated with mercaptoethanol and (14)C S-adenosylmethionine. RESULTS:
      Erythrocyte TMT activity of surgically treated cases of colitis was significantly
      elevated (p<0. 001) compared with control cases. TMT activity of rectal biopsies
      was significantly decreased (p<0.02) in acute but not quiescent ulcerative
      colitis, Crohn's colitis, or radiation colitis. CONCLUSIONS: Erythrocyte TMT
      activity was persistently elevated after proctocolectomy for Crohn's disease and
      ulcerative colitis. No primary defect of TMT activity was found in any case of
      unoperated colitis but mucosal activity was diminished with disease progression
      of ulcerative colitis. Studies of genetic control of TMT activity of erythrocytes
      in inflammatory bowel disease appear worthwhile.

PMID- 10896914
TI  - Bax is downregulated in inflamed colonic mucosa of ulcerative colitis.
AB  - BACKGROUND AND AIMS: One form of epithelial cell injury in inflamed colonic
      mucosa in ulcerative colitis (UC) is reported to involve apoptosis of these
      cells. Bcl-2 family proteins Bax and Bcl-2 are the major regulators of apoptosis.
      The aim of this study was to elucidate the involvement of the Bax/Bcl-2 system in
      induction of apoptosis of the inflamed colonic epithelium in UC. METHODS: Colonic
      epithelium was isolated from colonic biopsy specimens. Expression of CD95, Bax,
      Bcl-xL, and Bcl-2 proteins was determined by western blotting. Bax gene
      expression was assessed by both reverse transcription-polymerase chain reaction
      (RT-PCR) followed by Southern hybridisation and a real time PCR assay. RESULTS:
      Equal levels of expression of CD95, Bcl-xL, and Bcl-2 proteins were noted in
      normal and UC colonic epithelia. Equal levels of expression of Bax protein and
      mRNA were noted in epithelia of normal colon and inactive UC. Levels of
      expression of Bax protein and mRNA were markedly reduced in inflamed UC colonic
      epithelium. CONCLUSIONS: Our study showed for the first time downregulation of
      Bax in inflamed colonic epithelium of UC. The Bax/Bcl-2 system did not seem to be
      involved in induction of apoptosis of epithelial cells in the inflamed colonic
      mucosa of UC.

PMID- 10896913
TI  - Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune
      cell phenotype and TcR-gammadelta expression.
AB  - BACKGROUND AND AIMS: A histopathological feature considered indicative of
      ulcerative colitis (UC) is the so-called basal lymphoid aggregates. Their
      relevance in the pathogenesis of UC is, however, unknown. We have performed a
      comprehensive analysis of the immune cells in these aggregates most likely
      corresponding to the lymphoid follicular hyperplasia also described in other
      colitides. METHODS: Resection specimens of UC and normal colon were analysed by
      immunomorphometry, immunoflow cytometry, and immunoelectron microscopy, using a
      large panel of monoclonal antibodies. RESULTS: (1) In all cases of UC, colonic
      lamina propria contained numerous basal aggregates composed of lymphocytes,
      follicular dendritic cells, and CD80/B7.1 positive dendritic cells. (2)
      CD4(+)CD28(-) alphabeta T cells and B cells were the dominant cell types in the
      aggregates. (3) The aggregates contained a large fraction of cells that are
      normally associated with the epithelium: that is, gammadelta T cells (11 (7)%)
      and alpha(E)beta(7)(+) cells (26 (13)%). The gammadelta T cells used Vdelta1 and
      were CD4(-)CD8(-). Immunoelectron microscopy analysis demonstrated TcR-gammadelta
      internalisation and surface downregulation, indicating that the gammadelta T
      cells were activated and engaged in the disease process. (4) One third of cells
      in the aggregates expressed the antiapoptotic protein bcl-2. CONCLUSIONS: Basal
      lymphoid aggregates in UC colon are a consequence of anomalous lymphoid
      follicular hyperplasia, characterised by abnormal follicular architecture and
      unusual cell immunophenotypes. The aggregates increase in size with severity of
      disease, and contain large numbers of apoptosis resistant cells and activated
      mucosal gammadelta T cells. The latter probably colonise the aggregates as an
      immunoregulatory response to stressed lymphocytes or as a substitute for
      defective T helper cells in B cell activation. gammadelta T cells in the
      aggregates may be characteristic of UC.

PMID- 10896915
TI  - Autoantibodies against the specific epitope of human tropomyosin(s) detected by a
      peptide based enzyme immunoassay in sera of patients with ulcerative colitis show
      antibody dependent cell mediated cytotoxicity against HLA-DPw9 transfected L
      cells.
AB  - BACKGROUND AND AIMS: Recent studies suggest that tropomyosin (TM) may act as a
      putative autoantigen in ulcerative colitis (UC). Recently, we identified, by
      computer homology analysis, a specific peptide (HIAEDADRK) in human TM that can
      bind to HLA-DPw9. The aim of this study was to investigate the presence of
      autoantibodies against this peptide in UC. METHODS: Antibodies were measured by
      ELISA with a synthetic peptide in 20 healthy volunteers, 48 patients with UC, 26
      with Crohn's disease (CD), eight with primary sclerosing cholangitis (PSC), and
      six with primary biliary cirrhosis (PBC). The functional significance of
      antibodies was investigated by antibody dependent cell mediated cytotoxicity
      (ADCC) against DPw9 transfected L cells using a standard (51)Cr release assay.
      RESULTS: Optical density values (mean (SD)) of sera from patients with UC (1.40
      (0. 52)) and PSC (1.65 (0.12)) were significantly higher than those from healthy
      volunteers (0.32 (0.28)) (p<0.05), CD (0.50 (0.34)) (p<0.05) and PBC (0.14
      (0.09)) (p<0.05). Values in UC decreased with clinical improvement. The ADCC
      activity of UC sera correlated well with antibody titre against this synthetic
      peptide. CONCLUSIONS: Anti-TM antibody was detected in UC sera by a specific
      peptide based ELISA with high reproducibility. This peptide may be an antigenic
      epitope of TM involved in the immunopathogenesis of UC and, perhaps, PSC.

PMID- 10896916
TI  - Alpha(2) adrenoceptors regulate proliferation of human intestinal epithelial
      cells.
AB  - BACKGROUND AND AIMS: Previous studies on rodents have suggested that
      catecholamines stimulate proliferation of the intestinal epithelium through
      activation of alpha(2) adrenoceptors located on crypt cells. The occurrence of
      this effect awaits demonstration in humans and the molecular mechanisms involved
      have not yet been elucidated. Here, we examined the effect of alpha(2) agonists
      on a clone of Caco2 cells expressing the human alpha(2A) adrenoceptor. METHODS:
      Cells were transfected with a bicistronic plasmid containing the alpha2C10 and
      neomycin phosphotransferase genes. G418 resistant clones were assayed for
      receptor expression using radioligand binding. Receptor functionality was
      assessed by testing its ability to couple Gi proteins and to inhibit cAMP
      production. Mitogen activated protein kinase (MAPK) phosphorylation was followed
      by western blot, and cell proliferation was estimated by measuring protein and
      DNA content. RESULTS: Permanent transfection of Caco2 cells allowed us to obtain
      a clone (Caco2-3B) expressing alpha(2A) adrenoceptors at a density similar to
      that found in normal human intestinal epithelium. Caco2-3B retained morphological
      features and brush border enzyme expression characteristic of enterocytic
      differentiation. The receptor was coupled to Gi2/Gi3 proteins and its stimulation
      caused marked diminution of forskolin induced cAMP production. Treatment of Caco2
      3B with UK14304 (alpha(2) agonist) induced a rapid increase in the
      phosphorylation state of MAPK, extracellular regulated protein kinase 1 (Erk1),
      and 2 (Erk2). This event was totally abolished in pertussis toxin treated cells
      and in the presence of kinase inhibitors (genistein or PD98059). It was
      unaffected by protein kinase C downregulation but correlated with a transient
      increase in Shc tyrosine phosphorylation. Finally, sustained exposure of Caco2-3B
      to UK14304 resulted in modest but significant acceleration of cell proliferation.
      None of these effects was observed in the parental cell line Caco2. CONCLUSION:
      The results obtained in the present study support a regulatory role for alpha(2)
      adrenoceptors in intestinal cell proliferation.

PMID- 10896917
TI  - The Vienna classification of gastrointestinal epithelial neoplasia.
AB  - BACKGROUND: Use of the conventional Western and Japanese classification systems
      of gastrointestinal epithelial neoplasia results in large differences among
      pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic
      lesions. AIM: To develop common worldwide terminology for gastrointestinal
      epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed
      35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The
      extent of diagnostic agreement between those with Western and Japanese viewpoints
      was assessed by kappa statistics. The pathologists met in Vienna to discuss the
      results and to develop a new consensus terminology. RESULTS: The large
      differences between the conventional Western and Japanese diagnoses were
      confirmed (percentage of specimens for which there was agreement and kappa
      values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01
      for oesophageal lesions). There was much better agreement among pathologists (71%
      and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for
      oesophageal lesions) when the original assessments of the specimens were
      regrouped into the categories of the proposed Vienna classification of
      gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2)
      indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low
      grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade
      adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma),
      and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or
      beyond). CONCLUSION: The differences between Western and Japanese pathologists in
      the diagnostic classification of gastrointestinal epithelial neoplastic lesions
      can be resolved largely by adopting the proposed terminology, which is based on
      cytological and architectural severity and invasion status.

PMID- 10896918
TI  - Association of aldehyde dehydrogenase 2 gene polymorphism with multiple
      oesophageal dysplasia in head and neck cancer patients.
AB  - BACKGROUND: Multiple occurrences of oesophageal dysplasia are frequently observed
      in head and neck cancer patients, and closely associated with alcohol
      consumption. Acetaldehyde, the first metabolite of ethanol, is thought to play an
      important role in the carcinogenesis of the upper aerodigestive tract. AIM: To
      investigate if genetic polymorphism in alcohol metabolising enzymes (ADH3,
      alcohol dehydrogenase 3; ALDH2, aldehyde dehydrogenase 2) is associated with
      oesophageal multiple dysplasia in head and neck cancer patients. METHODS: Thirty
      one consecutive patients with head and neck cancer were included in the study.
      Multiple oesophageal dysplasia was detected endoscopically as multiple Lugol
      voiding lesions (multiple LVL) using the Lugol dye staining method. The ADH3 and
      ALDH2 genotypes were determined by polymerase chain reaction-restriction fragment
      length polymorphism. RESULTS: Among the 31 patients with head and neck cancer, 17
      had multiple LVL. Multiple LVL were closely associated with a second primary
      oesophageal carcinoma in head and neck cancer patients (odds ratio 60.7, 95% CI
      5.6-659). Furthermore, the mutant ALDH2 allele was significantly more prevalent
      in patients with multiple LVL (65% v 29%; p<0.05) whereas no difference was
      observed in ADH3 polymorphism. CONCLUSIONS: The mutant ALDH2 allele appears to be
      a risk indicator for multiple LVL in head and neck cancer patients. Accumulation
      of acetaldehyde due to low ALDH2 activity may play a critical role in cancerous
      changes throughout the mucosa in the upper aerodigestive tract.

PMID- 10896919
TI  - The E-cadherin gene (CDH1) variants T340A and L599V in gastric and colorectal
      cancer patients in Korea.
AB  - INTRODUCTION: Germline mutations in E-cadherin (CDH1) have been reported in
      families with early onset, diffuse gastric cancer. More recently, mutations in
      CDH1 have been described in colorectal cancer cell lines. AIMS: We have
      investigated if germline mutations in CDH1 occur among different groups of Korean
      gastric and colorectal cancer patients, with and without a positive family
      history. METHODS: We studied 131 patients and 168 normal controls (88 Korean and
      80 non-Korean). Patients were divided into five groups: group I, 20 gastric
      cancer patients with a family history; group II, 26 colorectal cancer patients
      with a family history of gastric cancer (those from familial adenomatous
      polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) kindred
      were excluded); group III, 16 HNPCC patients without identified germline
      mutations in hMLH1 and hMSH2; group IV, 35 gastric cancer patients without a
      family history; and group V, 34 colorectal cancer patients without a family
      history. Polymerase chain reaction, single strand conformational polymorphism
      analysis, direct sequencing, and genotyping for identified variants were
      performed. RESULTS: Several germline changes in CDH1 were found. In addition to
      previously described polymorphisms, we found three novel changes, two of which
      were missense changes (T340A and L599V). T340A was present in one patient in
      group III and one in group V. L599V was present in one patient in group II, in
      two in group III, and in one in group IV. T340A was not found in normal controls
      while L599V was present in two of 88 Korean controls. Patients with these
      variants may appear to have a tendency to early onset cancer with a positive
      family history, although differences in frequencies did not reach statistical
      significance. Genotyping results suggest that these variants might have a common
      origin, particularly T340A. CONCLUSION: We have described two new missense
      germline variants in CDH1 in various groups of Korean gastrointestinal cancer
      patients. Further work is required to assess if these variants increase the risk
      of gastrointestinal cancer.

PMID- 10896920
TI  - Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers.
AB  - BACKGROUND/AIMS: In 1998 the PPP2R1B gene encoding the A subunit of the
      serine/threonine protein phosphatase was identified as a putative tumour
      suppressor gene in lung and colon cancer in the chromosome region 11q22-24. The
      aim of the present study was to determine the type of alterations in primary
      rectal cancers as well as colon cancers and the correlation between these
      alterations and clinicopathological data. METHODS: Mutation analyses of the
      PPP2R1B gene sequence encoding the binding sites of the catalytic C subunit
      (Huntington elongation A subunit TOR (HEAT) repeats 11-15) and partial binding
      sites of the regulatory B subunit were carried out on cDNA samples from 30
      primary colorectal cancer specimens and corresponding normal tissues using a
      combination of the polymerase chain reaction and subsequent direct DNA
      sequencing. RESULTS: Five missense mutations producing amino acid substitutions
      were detected in the four colon cancer cases (13.3%; four of 30 colorectal
      cancers): (15)glycine (GGT) to alanine (GCT) and (499)leucine (TTA) to isoleucine
      (ATA) in the same case, and (498)valine (GTG) to glutamic acid (GAG), (500)valine
      (GTA) to glycine (GGA), and (365)serine (TCT) to proline (CCT). Of these five
      mutations, three (60%) were located in HEAT repeat 13 and four (80%) showed T to
      other nucleotide substitutions. In addition, a normal polymorphism, (478)leucine,
      was found. No correlation was found between these mutations and
      clinicopathological data. CONCLUSION: Our results suggest that the PPP2R1B gene
      is one of the true targets at 11q23, and its inactivation is involved in the
      development of all types of colorectal cancers.

PMID- 10896921
TI  - 5'-CpG island methylation of the LKB1/STK11 promoter and allelic loss at
      chromosome 19p13.3 in sporadic colorectal cancer.
AB  - BACKGROUND: In patients with Peutz-Jeghers syndrome (PJS), causative germline
      mutations in the LKB1/STK11 gene on chromosome 19p13.3 have been identified.
      Because of the loss of heterozygosity (LOH) at 19p13.3 in hamartomas and the
      cancer susceptibility of patients with PJS, LKB1/STK11 is suggested to act as a
      tumour suppressor. However, the frequency of genetic and epigenetic inactivation
      of LKB1/STK11 in sporadic tumours is unclear. AIMS: To investigate the LKB1/STK11
      gene for promoter hypermethylation and allelic loss in tumour specimens of
      patients with sporadic colorectal cancer. METHODS: DNA from 50 consecutive
      paraffin embedded sporadic colorectal adenocarcinomas and corresponding normal
      epithelium was extracted. After bisulphite treatment, specimens were analysed for
      methylation of the LKB1/STK11 promoter 5'-CpG island by methylation specific
      polymerase chain reaction (MSP). In addition, tumours were analysed for LOH of
      chromosome 19p13.3. In tumours exhibiting LOH, LKB1/STK11 was sequenced. RESULTS:
      MSP was successful in 48 of 50 tumour specimens. Of those, four (8%) demonstrated
      hypermethylation of the LKB1/STK11 promoter 5'-CpG island. Moreover, LOH at
      either D19S886 or D19S878 was observed in five of 38 (13%) informative tumours.
      All five tumours showing LOH at 19p13.3 were advanced and four of five were
      located in the left sided colon. There was no correlation between LOH and
      LKB1/STK11 promoter hypermethylation or somatic mutation. CONCLUSIONS: In
      sporadic colorectal cancer, hypermethylation of the LKB1/STK11 promoter and
      allelic loss at the STK 11 gene locus are rare events. LOH at 19p13.3 was
      associated with advanced tumour stage and left sided location but not with
      LKB1/STK11 promoter hypermethylation or somatic mutation.

PMID- 10896922
TI  - Prevalence of hepatitis C among pregnant women attending an inner London
      obstetric department: uptake and acceptability of named antenatal testing.
AB  - OBJECTIVE: To examine the value of universal antenatal screening for hepatitis C
      virus (HCV) infection among an inner London population, with regard to
      prevalence, uptake, and acceptability of testing, and identification of new
      cases. DESIGN: Serum analysis for antibodies against HCV in pregnant women
      following informed consent ("opt out" policy). Samples positive for HCV
      antibodies were tested for the presence of HCV RNA by polymerase chain reaction.
      Information on hepatitis C was provided for all women. Acceptability of antenatal
      HCV testing and identification of risk factors for infection were assessed
      through the use of questionnaires randomly distributed among a cohort of 300
      pregnant women. SETTING: Antenatal clinics at St Mary's Hospital, London, serving
      a multiethnic population. SUBJECTS: A total of 4825 pregnant women booking for
      antenatal care between November 1997 and April 1999. RESULTS: The overall
      prevalence of anti-HCV was 0.8% and HCV viraemia was 0.6%. Ninety eight per cent
      of samples (n=4729) were tested; 0.2% of women had a false positive result. In
      207 women who completed a questionnaire regarding our testing policy, 84% made a
      positive decision to be tested for anti-HCV and 92% said that HCV testing should
      be offered to all pregnant women. The majority (22/32-69%) of HCV infected women
      were newly diagnosed and although HCV positive women were significantly more
      likely to have a history of drug abuse, most (16/22-73%) new cases had no
      identified risk factors for HCV infection at booking. CONCLUSION: The prevalence
      of anti-HCV in an inner London multiethnic antenatal population is high (0.8%).
      Routine screening for HCV is acceptable to pregnant women. The majority of women
      diagnosed during their current pregnancy would not have been identified as HCV
      infected by epidemiological risk factors at the time of booking.

PMID- 10896923
TI  - Mechanisms of endotoxin tolerance in patients with alcoholic liver cirrhosis:
      role of interleukin 10, interleukin 1 receptor antagonist, and soluble tumour
      necrosis factor receptors as well as effector cell desensitisation.
AB  - BACKGROUND: In patients with alcoholic liver cirrhosis, endotoxaemia is a
      frequent finding. Unknown mechanisms, however, prevent typical clinical symptoms
      of endotoxaemia in many patients. METHODS: We determined plasma levels of pro-
      and anti-inflammatory mediators, ex vivo cytokine secretion capacity, and
      expression of tumour necrosis factor (TNF) receptors on phagocytic blood cells in
      49 patients with alcoholic cirrhosis and 41 age matched healthy controls.
      RESULTS: In addition to increased levels of proinflammatory cytokines in
      cirrhotic patients, we observed consistent upregulation of the anti-inflammatory
      mediators interleukin 10 (IL-10) (plasma 15.75 (1. 6) v 6.6 (1.3) pg/ml
      (p<0.001); ex-vivo 108.4 (22.0) v 40.1 (7.4) pg/ml (p<0.05)), interleukin 1
      receptor antagonist (plasma 527.1 (83) v 331.4 (56) pg/ml (p<0.05); ex vivo 19.9
      (3.4) v 10.2 (2.7) ng/ml (p<0.01)), and soluble TNF receptors (sTNF-R) in plasma
      (sTNF-RI 3157.2 (506.2) v 607.9 (300.3) pg/ml; sTNF-RII 3331.0 (506. 2) v 1066.4
      (225.1) pg/ml (p<0.001 for both)). Desensitisation at the target cell level was
      indicated by reduced expression of TNF receptor I on granulocytes (64.8 (6.5) v
      40.1 (7.3)% positive cells; p<0.05) and unaltered plasma levels of soluble E
      selectin. CONCLUSION: In patients with alcoholic liver cirrhosis, upregulation of
      the pro- and anti-inflammatory cytokine system and simultaneous desensitisation
      of effector cells could explain the restricted systemic inflammatory response to
      chronic endotoxaemia. This alteration in immune status may lead to impairment of
      host defences against infections which are frequent complications of alcoholic
      cirrhosis.

PMID- 10896925
TI  - Very late onset small intestinal B cell lymphoma associated with primary
      intestinal lymphangiectasia and diffuse cutaneous warts.
AB  - As only a handful of lymphoma cases have been reported in conjunction with
      primary intestinal lymphangiectasia, it is not yet clear if this association is
      merely fortuitous or related to primary intestinal lymphangiectasia induced
      immune deficiency. We report on two female patients, 50 and 58 years old, who
      developed small intestinal high grade B cell lymphoma a long time (45 and 40
      years, respectively) after the initial clinical manifestations of primary
      intestinal lymphangiectasia. They presented with a longstanding history of
      fluctuating protein losing enteropathy, multiple cutaneous plane warts, and
      markedly dilated mucosal and submucosal lymphatic channels in duodenal biopsies.
      One had a large ulcerated tumour of the proximal ileum and the other diffuse
      ileal infiltration. In both, histological examination showed centroblastic high
      grade B cell lymphoma associated with duodenojejuno-ileal mucosal and submucosal
      lymphangiectasia. They were subsequently successfully treated with surgery and
      postoperative chemotherapy (AVmCP: adriamycin, cyclophosphamide, Vm26, and
      prednisolone), and chemotherapy alone (PACOB: adriamycin, cyclophosphamide,
      vincristine, bleomycine, and prednisolone), respectively. A three year follow up
      in both cases showed persistent diffuse lymphangiectasia without evidence of
      lymphoma. The present findings support the hypothesis that primary intestinal
      lymphangiectasia is associated with lymphoma development.

PMID- 10896924
TI  - Long term outcome after transjugular intrahepatic portosystemic stent-shunt in
      non-transplant cirrhotics with hepatorenal syndrome: a phase II study.
AB  - BACKGROUND: Recent small studies on hepatorenal syndrome (HRS) indicate some
      clinical benefit after transjugular intrahepatic portosystemic stent-shunt (TIPS)
      but sufficient long term data are lacking. AIM: We studied prospectively
      feasibility, safety, and long term survival after TIPS in 41 non-transplantable
      cirrhotics with HRS (phase II study). PATIENTS AND METHODS: HRS was diagnosed
      using current criteria (severe (type I) HRS, n=21; moderate (type II) HRS, n=20).
      Thirty one patients (14 type I, 17 type II) received TIPS (8-10 mm) while
      advanced liver failure excluded shunting in 10. During follow up (median 24
      months) we analysed renal function and survival (Kaplan-Meier). RESULTS: TIPS
      markedly reduced the portal pressure gradient (21 (5) to 13 (4) mm Hg (mean
      (SD)); p<0.001) with one procedure related death (3.2%). Renal function
      deteriorated without TIPS but improved (p<0.001) within two weeks after TIPS
      (creatinine clearance 18 (15) to 48 (42) ml/min; sodium excretion 9 (16) to 77
      (78) mmol/24 hours) and stabilised thereafter. Following TIPS, three, six, 12,
      and 18 month survival rates were 81%, 71%, 48%, and 35%, respectively. As only
      10% of non-shunted patients survived three months, total survival rates were 63%,
      56%, 39%, and 29%, respectively. Multivariate Cox regression analysis revealed
      bilirubin (p<0.001) and HRS type (p<0.05) as independent survival predictors
      after TIPS. CONCLUSIONS: TIPS provides long term renal function and probably
      survival benefits in the majority of non-transplantable cirrhotics with HRS.
      These data warrant controlled trials evaluating TIPS in the management of HRS.

PMID- 10896926
TI  - Needle tract recurrence of hepatocellular carcinoma after liver transplantation.

PMID- 10896927
TI  - Epigenetics of inflammatory bowel disease.

PMID- 10896928
TI  - Is the colonic reparative cell lineage yet to be discovered?

PMID- 10896930
TI  - Timing of transfusion, anti-HBc, and hepatitis C virus related hepatocellular
      carcinoma.

PMID- 10896929
TI  - Interleukin 6 and liver regeneration.

PMID- 10896931
TI  - Mutations in the hinge of a dynamic loop broadly influence functional properties
      of fructose-1,6-bisphosphatase.
AB  - Loop 52-72 of porcine fructose-1,6-bisphosphatase may play a central role in the
      mechanism of catalysis and allosteric inhibition by AMP. The loop pivots between
      different conformational states about a hinge located at residues 50 and 51. The
      insertion of proline separately at positions 50 and 51 reduces k(cat) by up to 3
      fold, with no effect on the K(m) for fructose 1,6-bisphosphate. The K(a) for
      Mg(2+) in the Lys(50) --> Pro mutant increases approximately 15-fold, whereas
      that for the Ala(51) --> Pro mutant is unchanged. Although these mutants retain
      wild-type binding affinity for AMP and the fluorescent AMP analog 2'(3')-O
      (trinitrophenyl)adenosine 5'-monophosphate, the K(i) for AMP increases 8000- and
      280-fold in the position 50 and 51 mutants, respectively. In fact, the mutation
      Lys(50) --> Pro changes the mechanism of AMP inhibition with respect to Mg(2+)
      from competitive to noncompetitive and abolishes K(+) activation. The K(i) for
      fructose 2,6-bisphosphate increases approximately 20- and 30-fold in the Lys(50) 
      -> Pro and Ala(51) --> Pro mutants, respectively. Fluorescence from a tryptophan
      introduced by the mutation of Tyr(57) suggests an altered conformational state
      for Loop 52-72 due to the proline at position 50. Evidently, the Pro(50) mutant
      binds AMP with high affinity at the allosteric site, but the mechanism of
      allosteric regulation of catalysis has been disabled.

PMID- 10896932
TI  - A di-aromatic motif in the cytosolic tail of the mannose receptor mediates
      endosomal sorting.
AB  - The mannose receptor (MR), the prototype of a new family of multilectin receptor
      proteins important in innate immunity, undergoes rapid internalization and
      recycling from the endosomal system back to the cell surface. Sorting of the MR
      in endosomes prevents the receptor from entering lysosomes where it would be
      degraded. Here, we focused on a diaromatic sequence (Tyr(18)-Phe(19)) in the MR
      cytoplasmic tail as an endosomal sorting signal. The subcellular distribution of
      chimeric constructs between the MR and the cation-dependent mannose 6-phosphate
      receptor was assessed by Percoll density gradients and cell surface assays.
      Unlike the wild type constructs, mutant receptors with alanine substitutions of
      Tyr(18)-Phe(19) were highly missorted to lysosomes, indicating that the di
      aromatic motif of the MR cytoplasmic tail mediates sorting in endosomes. Within
      this sequence Tyr(18) is the key residue with Phe(19) contributing to this
      function. Moreover, Tyr(18) was also found to be essential for internalization,
      consistent with the presence of overlapping signals for internalization and
      endosomal sorting in the cytosolic tail of the MR. A di-aromatic amino acid
      sequence in the cytosolic tail has now been shown to function in two receptors
      known to be internalized from the plasma membrane, the MR and the cation
      dependent mannose 6-phosphate receptor. This feature therefore appears to be a
      general determinant for endosomal sorting.

PMID- 10896933
TI  - A CDC6 protein-binding peptide selected using a bacterial two-hybrid-like system
      is a cell cycle inhibitor.
AB  - Peptides or small molecules able to modulate protein-protein interactions hold
      promise as tools with which to probe and manipulate biological pathways. An
      important issue in this nascent field is to evaluate different methods with which
      to search libraries for molecules that modulate the function of specific target
      proteins. One strategy is to screen libraries for molecules that bind
      specifically to a protein known to be critical in the pathway of interest, with
      the expectation that the molecules isolated will recognize regions of the target
      protein important for its function and thereby exhibit biological activity. Here,
      a peptide library was screened using a two-hybrid-like system for molecules able
      to bind human CDC6 protein (CDC6p), required for the initiation of DNA
      replication in eukaryotic cells. From a collection of over a million peptides, a
      single species that exhibited good affinity and specificity for binding CDC6p was
      obtained. When expressed in human cells, the peptide inhibited cell cycle
      progression and exhibited other properties expected of a CDC6p inhibitor. This
      approach, which does not require detailed knowledge of the mechanism of action of
      a protein target, may be generally useful for isolating peptides capable of
      manipulating biological pathways.

PMID- 10896934
TI  - Threonine phosphorylation of the beta 3 integrin cytoplasmic tail, at a site
      recognized by PDK1 and Akt/PKB in vitro, regulates Shc binding.
AB  - The mechanism of outside-in signaling by integrins parallels that for growth
      factor receptors. In both pathways, phosphorylation of a cytoplasmic segment on
      tyrosine generates a docking site for proteins containing Src homology 2 (SH2)
      and phosphotyrosine binding domains. We recently observed that phosphorylation of
      a threonine (Thr-753), six amino acids proximal to tyrosine 759 in beta(3) of the
      platelet specific integrin alpha(IIb)beta(3), inhibits outside-in signaling
      through this receptor. We hypothesized that the presence of phosphothreonine 753
      either renders beta(3) a poor substrate for tyrosine kinases or inhibits the
      docking capabilities of the tyrosyl-phosphorylated form of beta(3.) The first
      alternative was tested by comparing the phosphorylation of beta(3) model peptides
      by the tyrosine kinase pp60(c-src) and we found that the presence of a phosphate
      group on a residue corresponding to Thr-753 did not detectably alter the kinetics
      of tyrosine phosphorylation. However, the presence of phosphate on this threonine
      inhibited the binding of Shc to tyrosyl-phosphorylated beta(3) peptide. The
      inhibitory effect of the phosphate group could be mimicked by substituting an
      aspartic acid for Thr-753, suggesting that a negative charge at this position
      modulates the binding of Shc and possibly other phosphotyrosine binding domain-
      and SH2-containing proteins. A survey of several protein kinases revealed that
      Thr-753 was avidly phosphorylated by PDK1 and Akt/PKB in vitro. These
      observations suggest that activation of PDK1 and/or Akt/PKB in platelets may
      modulate the binding activity and/or specificity of beta(3) for signaling
      molecules.

PMID- 10896935
TI  - Ras oncoprotein induces CD44 cleavage through phosphoinositide 3-OH kinase and
      the rho family of small G proteins.
AB  - CD44 is a cell surface adhesion molecule for several extracellular matrix
      components. We previously showed that CD44 expressed in cancer cells is
      proteolytically cleaved at the ectodomain through membrane-anchored
      metalloproteases and that CD44 cleavage plays a critical role in cancer cell
      migration. Therefore, cellular signals that promote the migration and metastatic
      activity of cancer cells may regulate the CD44 ectodomain cleavage. Here, we
      demonstrate that the expression of the dominant active mutant of Ha-Ras (Ha
      Ras(Val-12)) induces redistribution of CD44 to the newly generated membrane
      ruffling area and CD44 ectodomain cleavage. The migration assay revealed that the
      CD44 cleavage contributes to the Ha-Ras(Val-12)-induced migration of NIH3T3 cells
      on hyaluronate substrate. Treatment with LY294002, an inhibitor for
      phosphoinositide 3-OH kinase (PI3K), significantly inhibits Ha-Ras(Val-12)
      induced CD44 cleavage, whereas that with PD98059, an inhibitor for MEK, does not.
      The active mutant p110 subunit of PI3K has also been shown to enhance the CD44
      cleavage, suggesting that PI3K mediates the Ras-induced CD44 cleavage. Moreover,
      the expression of dominant negative mutants of Cdc42 and Rac1 inhibits the Ha
      Ras(Val-12)-induced CD44 cleavage. These results suggest that Ras > PI3K >
      Cdc42/Rac1 pathway plays an important role in CD44 cleavage and may provide a
      novel molecular basis to explain how the activated Ras facilitates cancer cell
      migration.

PMID- 10896936
TI  - Zinc transport and metallothionein secretion in the intestinal human cell line
      Caco-2.
AB  - Caco-2, a human cell line, displays several biochemical and morphological
      characteristics of differentiated enterocytes. Among these is the ability to
      transport zinc from the apical to the basal compartment. This process was
      enhanced following exposure by the apical compartment to increasing
      concentrations of the metal. High pressure liquid chromatography fractionation of
      the media obtained from cells labeled with radioactive zinc showed that
      metallothioneins (MTs), small metal-binding, cysteine-rich proteins), were
      present in the apical and basal media of controls as well as in cells grown in
      the presence of high concentrations of zinc. Following exposure to the metal, the
      levels of Zn-MTs in the apical medium increased, while in the basal compartment
      the greatest part of zinc appeared in a free form with minor changes in the
      levels of basal MTs. Metabolic labeling experiments with radioactive cysteine
      confirmed the apical secretion of MTs. A stable transfectant clone of Caco-2
      cells (CL11) was selected for its ability to express constitutively high levels
      of the mouse metallothionein I protein. This cell line showed an enhanced
      transport of the metal following exposure to high concentrations of zinc and a
      constitutive secretion of the mouse metallothionein I protein in the apical
      compartment. Together, these findings strongly support the hypothesis of a
      functional role between the biosynthesis and secretion of MTs and the transport
      of zinc in intestinal cells.

PMID- 10896937
TI  - Assembly of partial TFIID complexes in mammalian cells reveals distinct
      activities associated with individual TATA box-binding protein-associated
      factors.
AB  - The TATA box-binding protein (TBP) and TBP-associated factors (TAF(II)s) compose
      the general transcription factor TFIID. The TAF(II) subunits mediate activated
      transcription by RNA polymerase II by interacting directly with site-specific
      transcriptional regulators. TAF(II)s also participate in promoter recognition by
      contacting core promoter elements in the context of TFIID. To further dissect the
      contribution of individual TAF(II) subunits to mammalian TFIID function, we
      employed a vaccinia virus-based protein expression system to study protein
      protein interactions and complex assembly. We identified the domains of human (h)
      TAF(II)130 required for TAF(II)-TAF(II) interactions and formation of a complex
      with hTBP, hTAF(II)100, and hTAF(II)250. Functional analysis of partial TFIID
      complexes formed in vivo indicated that hTAF(II)130 was required for
      transcriptional activation by Sp1 in vitro. DNase I footprinting experiments
      demonstrated that purified hTBP/hTAF(II)250 complex reconstituted with or without
      additional TAF(II)s was significantly reduced for TATA box binding (as much as 9
      fold) compared with free hTBP. By contrast, hTAF(II)130 stabilized binding of
      hTBP to the TATA box, whereas hTAF(II)100 had little effect. Thus, our
      biochemical analysis supports the notion that TAF(II)s possess distinct functions
      to regulate the activity of TFIID.

PMID- 10896938
TI  - p130Cas regulates the activity of AND-34, a novel Ral, Rap1, and R-Ras guanine
      nucleotide exchange factor.
AB  - We previously identified a novel murine protein, AND-34, with a carboxyl-terminal
      domain homologous to Ras family guanine nucleotide exchange factors (GEFs), which
      bound to the focal adhesion docking protein p130(Cas). Work by others has
      implicated both the human homologue of AND-34, BCAR3, and human p130(Cas), BCAR1,
      in the resistance of breast cancer cells to the anti-estrogen tamoxifen. Here we
      report that AND-34 displays GEF activity on RalA, Rap1A, and R-Ras but not Ha-Ras
      GTPases in cells. In contrast to several other Ral-GEFs, the Ral GEF activity of
      AND-34 is not augmented by constitutively active Ha-Ras(Val-12), consistent with
      the absence of a detectable Ras-binding domain. Efficient binding to AND-34
      required both the Src-binding domain and a flanking carboxyl-terminal region of
      p130(Cas). The p130(Cas)-binding site mapped to a carboxyl-terminal sequence
      within the AND-34 GEF domain. Overexpression of p130(Cas), but not an AND-34
      binding mutant of p130(Cas), inhibited the Ral GEF activity of co-transfected AND
      34. This work identifies a new potential function for p130(Cas) and a new
      regulatory pathway involved in the control of Ral, Rap, and R-Ras GTPases that
      may participate in the progression of breast cancer cells to tamoxifen
      resistance.

PMID- 10896939
TI  - The upstream region of the Rpe65 gene confers retinal pigment epithelium-specific
      expression in vivo and in vitro and contains critical octamer and E-box binding
      sites.
AB  - RPE65 is essential for all-trans- to 11-cis-retinoid isomerization, the hallmark
      reaction of the retinal pigment epithelium (RPE). Here, we identify regulatory
      elements in the Rpe65 gene and demonstrate their functional relevance to Rpe65
      gene expression. We show that the 5' flanking region of the mouse Rpe65 gene,
      like the human gene, lacks a canonical TATA box and consensus GC and CAAT boxes.
      The mouse and human genes do share several cis-acting elements, including an
      octamer, a nuclear factor one (NFI) site, and two E-box sites, suggesting a
      conserved mode of regulation. A mouse Rpe65 promoter/beta-galactosidase transgene
      containing bases -655 to +52 (TR4) of the mouse 5' flanking region was sufficient
      to direct high RPE-specific expression in transgenic mice, whereas shorter
      fragments (-297 to +52 or -188 to +52) generated only background activity.
      Furthermore, transient transfection of analogous TR4/luciferase constructs also
      directed high reporter activity in the human RPE cell line D407 but weak activity
      in the non-RPE cell lines HeLa, HepG2, and HS27. Functional binding of potential
      transcription factors to the octamer sequence, AP-4, and NFI sites was
      demonstrated by directed mutagenesis, electrophoretic mobility shift assay, and
      cross-linking. Mutations of these sites abolished binding and corresponding
      transcriptional activity and indicated that octamer and E-box transcription
      factors synergistically regulate the RPE65 promoter function. Thus, we have
      identified the regulatory region in the Rpe65 gene that accounts for tissue
      specific expression in the RPE and found that octamer and E-box transcription
      factors play a critical role in the transcriptional regulation of the Rpe65 gene.

PMID- 10896940
TI  - Scavenger receptor-BI inhibits ATP-binding cassette transporter 1- mediated
      cholesterol efflux in macrophages.
AB  - Scavenger receptor BI (SR-BI) facilitates the efflux of cellular cholesterol to
      plasma high density lipoprotein (HDL). Recently, the ATP-binding cassette
      transporter 1 (ABC1) was identified as a key mediator of cholesterol efflux to
      apolipoproteins and HDL. The goal of the present study was to determine a
      possible interaction between the SR-BI and ABC1 cholesterol efflux pathways in
      macrophages. Free cholesterol efflux to HDL was increased ( approximately 2.2
      fold) in SR-BI transfected RAW macrophages in association with increased SR-BI
      protein levels. Treatment of macrophages with 8-bromo-cAMP (cAMP) resulted in a
      4.1-fold increase in ABC1 mRNA level and also increased cholesterol efflux to HDL
      (2.2-fold) and apoA-I (5.5-fold). However, in SR-BI transfected RAW cells, cAMP
      treatment produced a much smaller increment in cholesterol efflux to HDL (1.1
      fold) or apoA-I (3.3-fold) compared with control cells. In macrophages loaded
      with cholesterol by acetyl-LDL treatment, SR-BI overexpression did not increase
      cholesterol efflux to HDL but did inhibit cAMP-mediated cholesterol efflux to
      apoA-I or HDL. SR-BI neutralizing antibody led to a dose- and time-dependent
      increase of cAMP-mediated cholesterol efflux in both SR-BI transfected and
      control cells, indicating that SR-BI inhibits ABC1-mediated cholesterol efflux
      even at low SR-BI expression level. Transfection of a murine ABC1 cDNA into 293
      cells led to a 2.3-fold increase of cholesterol efflux to apoA-I, whereas co
      transfection of SR-BI with ABC1 blocked this increase in cholesterol efflux. SR
      BI and ABC1 appear to have distinct and competing roles in mediating cholesterol
      flux between HDL and macrophages. In nonpolarized cells, SR-BI promotes the
      reuptake of cholesterol actively effluxed by ABC1, creating a futile cycle.

PMID- 10896941
TI  - Type IV collagen of the glomerular basement membrane. Evidence that the chain
      specificity of network assembly is encoded by the noncollagenous NC1 domains.
AB  - The ultrafiltration function of the glomerular basement membrane (GBM) of the
      kidney is impaired in genetic and acquired diseases that affect type IV collagen.
      The GBM is composed of five (alpha1 to alpha5) of the six chains of type IV
      collagen, organized into an alpha1.alpha2(IV) and an alpha3.alpha4.alpha5(IV)
      network. In Alport syndrome, mutations in any of the genes encoding the
      alpha3(IV), alpha4(IV), and alpha5(IV) chains cause the absence of the alpha3.
      alpha4.alpha5 network, which leads to progressive renal failure. In the present
      study, the molecular mechanism underlying the network defect was explored by
      further characterization of the chain organization and elucidation of the
      discriminatory interactions that govern network assembly. The existence of the
      two networks was further established by analysis of the hexameric complex of the
      noncollagenous (NC1) domains, and the alpha5 chain was shown to be linked to the
      alpha3 and alpha4 chains by interaction through their respective NC1 domains. The
      potential recognition function of the NC1 domains in network assembly was
      investigated by comparing the composition of native NC1 hexamers with hexamers
      that were dissociated and reconstituted in vitro and with hexamers assembled in
      vitro from purified alpha1-alpha5(IV) NC1 monomers. The results showed that NC1
      monomers associate to form native-like hexamers characterized by two distinct
      populations, an alpha1.alpha2 and alpha3.alpha4.alpha5 heterohexamer. These
      findings indicate that the NC1 monomers contain recognition sequences for
      selection of chains and protomers that are sufficient to encode the assembly of
      the alpha1.alpha2 and alpha3.alpha4.alpha5 networks of GBM. Moreover, hexamer
      formation from the alpha3, alpha4, and alpha5 NC1 monomers required co-assembly
      of all three monomers, suggesting that mutations in the NC1 domain in Alport
      syndrome may disrupt the assembly of the alpha3.alpha4.alpha5 network by
      interfering with the assembly of the alpha3.alpha4.alpha5 NC1 hexamer.

PMID- 10896942
TI  - Molecular properties of the Goodpasture epitope.
AB  - Goodpasture disease fulfils all criteria for a classical autoimmune disease,
      where autoantibodies targeted against the non-collagenous domain of the alpha3
      chain of collagen IV initiates an inflammatory destruction of the basement
      membrane in kidney glomeruli and lung alveoli. This leads to a rapidly
      progressive glomerulonephritis and severe pulmonary hemorrhage. Previous studies
      have indicated a limited epitope for the toxic antibodies in the N-terminal part
      of the non-collagenous domain. The epitope has been partially characterized by
      recreating the epitope in the non-reactive alpha1-chain by exchanging nine
      residues to the corresponding ones of alpha3. In this study we have investigated
      to what extent each of these amino acids contribute to the antibody binding in
      different patient sera. The results show that seven of the nine substitutions are
      enough to get an epitope that is recognized equally well as the native alpha3
      chain by all sera from 20 clinically verified Goodpasture patients. Furthermore,
      the patient sera reactivity against the different recombinant chains used in the
      study are very similar, with some minor exceptions, strongly supporting a highly
      defined and restricted epitope. We are convinced that the restriction of the
      epitope is of significant importance for the understanding of the etiology of the
      disease. Thereby also making every step on the way to characterization of the
      epitope a crucial step on the way to specific therapy for the disease.

PMID- 10896943
TI  - Crystal structures of apo- and holo-bovine alpha-lactalbumin at 2. 2-A resolution
      reveal an effect of calcium on inter-lobe interactions.
AB  - High affinity binding of Ca(2+) to alpha-lactalbumin (LA) stabilizes the native
      structure and is required for the efficient generation of native protein with
      correct disulfide bonds from the reduced denatured state. A progressive increase
      in affinity of LA conformers for Ca(2+) as they develop increasingly native
      structures can account for the tendency of the apo form to assume a molten
      globule state and the large acceleration of folding by Ca(2+). To investigate the
      effect of calcium on structure of bovine LA, x-ray structures have been
      determined for crystals of the apo and holo forms at 2.2-A resolution. In both
      crystal forms, which were grown at high ionic strength, the protein is in a
      similar global native conformation consisting of alpha-helical and beta
      subdomains separated by a cleft. Even though alternative cations and Ca(2+)
      liganding solvent molecules are absent, removal of Ca(2+) has only minor effects
      on the structure of the metal-binding site and a structural change was observed
      in the cleft on the opposite face of the molecule adjoining Tyr(103) of the
      helical lobe and Gln(54) of the beta-lobe. Changes include increased separation
      of the lobes, loss of a buried solvent molecule near the Ca(2+)-binding site, and
      the replacement of inter- and intra-lobe H-bonds of Tyr(103) by interactions with
      new immobilized water molecules. The more open cleft structure in the apo protein
      appears to be an effect of calcium binding transmitted via a change in
      orientation of helix H3 relative to the beta-lobe to the inter-lobe interface.
      Calcium is well known to promote the folding of LA. The results from the
      comparison of apo and holo structures of LA provide high resolution structural
      evidence that the acceleration of folding by Ca(2+) is mediated by an effect on
      interactions between the two subdomains.

PMID- 10896945
TI  - Functional roles of the two domains of phosducin and phosducin-like protein.
AB  - Phosducin and phosducin-like protein regulate G protein signaling pathways by
      binding the betagamma subunit complex (Gbetagamma) and blocking Gbetagamma
      association with Galpha subunits, effector enzymes, or membranes. Both proteins
      are composed of two structurally independent domains, each constituting
      approximately half of the molecule. We investigated the functional roles of the
      two domains of phosducin and phosducin-like protein in binding retinal
      G(t)betagamma. Kinetic measurements using surface plasmon resonance showed that:
      1) phosducin bound G(t)betagamma with a 2. 5-fold greater affinity than phosducin
      like protein; 2) phosphorylation of phosducin decreased its affinity by 3-fold,
      principally as a result of a decrease in k(1); and 3) most of the free energy of
      binding comes from the N-terminal domain with a lesser contribution from the C
      terminal domain. In assays measuring the association of G(t)betagamma with
      G(t)alpha and light-activated rhodopsin, both N-terminal domains inhibited
      binding while neither of the C-terminal domains had any effect. In assays
      measuring membrane binding of G(t)betagamma, both the N- and C-terminal domains
      inhibited membrane association, but much less effectively than the full-length
      proteins. This inhibition could only be described by models that included a
      change in G(t)betagamma to a conformation that did not bind the membrane. These
      models yielded a free energy change of +1.5 +/- 0.25 kcal/mol for the transition
      from the G(t)alpha-binding to the Pd-binding conformation of G(t)betagamma.

PMID- 10896946
TI  - Lipid raft association of carboxypeptidase E is necessary for its function as a
      regulated secretory pathway sorting receptor.
AB  - Membrane carboxypeptidase E (CPE) is a sorting receptor for targeting
      prohormones, such as pro-opiomelanocortin, to the regulated secretory pathway in
      endocrine cells. Its membrane association is necessary for it to bind a
      prohormone sorting signal at the trans-Golgi network (TGN) to facilitate
      targeting. In this study, we examined the lipid interaction of CPE in bovine
      pituitary secretory granule membranes, which are derived from the TGN. We show
      that CPE is associated with detergent-resistant lipid domains, or rafts, within
      secretory granule membranes. Lipid analysis revealed that these rafts are
      enriched in glycosphingolipids and cholesterol. Pulse-chase and subcellular
      fractionation experiments in AtT-20 cells show that the association of CPE with
      membrane rafts occurred only after it reached the Golgi. Cholesterol depletion
      resulted in dissociation of CPE from secretory granule membranes and decreased
      the binding of prohormones to membranes. In vivo cholesterol depletion using
      lovastatin resulted in the lack of sorting of CPE and its cargo to the regulated
      secretory pathway. We propose that the sorting receptor function of CPE
      necessitates its interaction with glycosphingolipid-cholesterol rafts at the TGN,
      thereby anchoring it in position to bind to its prohormone cargo.

PMID- 10896944
TI  - Bone morphogenetic protein-1 processes probiglycan.
AB  - Bone morphogenetic protein-1 (BMP-1) is a metalloprotease that plays important
      roles in regulating the deposition of fibrous extracellular matrix in
      vertebrates, including provision of the procollagen C-proteinase activity that
      processes the major fibrillar collagens I-III. Biglycan, a small leucine-rich
      proteoglycan, is a nonfibrillar extracellular matrix component with functions
      that include the positive regulation of bone formation. Biglycan is synthesized
      as a precursor with an NH(2)-terminal propeptide that is cleaved to yield the
      mature form found in vertebrate tissues. Here, we show that BMP-1 cleaves
      probiglycan at a single site, removing the propeptide and producing a biglycan
      molecule with an NH(2) terminus identical to that of the mature form found in
      tissues. BMP-1-related proteases mammalian Tolloid and mammalian Tolloid-like 1
      (mTLL-1) are shown to have low but detectable levels of probiglycan-cleaving
      activity. Comparison shows that wild type mouse embryo fibroblasts (MEFs) produce
      only fully processed biglycan, whereas MEFs derived from embryos homozygous null
      for the Bmp1 gene, which encodes both BMP-1 and mammalian Tolloid, produce
      predominantly unprocessed probiglycan, and MEFs homozygous null for both the Bmp1
      gene and the mTLL-1 gene Tll1 produce only unprocessed probiglycan. Thus, all
      detectable probiglycan-processing activity in MEFs is accounted for by the
      products of these two genes.

PMID- 10896949
TI  - alpha-catenin inhibits beta-catenin signaling by preventing formation of a beta
      catenin*T-cell factor*DNA complex.
AB  - alpha-Catenin and beta-catenin link cadherins to the cytoskeleton at adherens
      junctions. beta-Catenin also associates with members of the T-cell factor (Tcf)
      family of transcription factors, and mutations in beta-catenin lead to activation
      of Tcf-dependent transcription and increased cell growth. Although the loss of
      alpha-catenin expression can also promote cell growth, the role of endogenous
      alpha-catenin in beta-catenin signaling is unclear. Here we show that loss of
      alpha-catenin expression in a colon cancer cell line correlates with increased
      Tcf-dependent transcription. The presence of alpha-catenin in colon cancer cell
      nuclei suggests that it inhibits transcription directly, and, in agreement with
      this, ectopic expression of alpha-catenin in the nucleus represses Tcf-dependent
      transcription. Furthermore, recombinant alpha-catenin disrupts the interaction
      between the beta-catenin.Tcf complex and DNA. We conclude that alpha-catenin
      inhibits beta-catenin signaling in the nucleus by interfering with the formation
      of a beta-catenin. Tcf.DNA complex.

PMID- 10896947
TI  - Fibroblast growth factor (FGF)-2 directly stimulates mature osteoclast function
      through activation of FGF receptor 1 and p42/p44 MAP kinase.
AB  - We previously reported that fibroblast growth factor-2 (FGF-2) acts not only on
      osteoblasts to stimulate osteoclastic bone resorption indirectly but also on
      mature osteoclasts directly. In this study, we investigated the mechanism of this
      direct action of FGF-2 on mature osteoclasts using mouse and rabbit osteoclast
      culture systems. FGF-2 stimulated pit formation resorbed by isolated rabbit
      osteoclasts moderately from low concentrations (>/=10(-12) m), whereas at high
      concentrations (>/=10(-9) m) it showed stimulation on pit formation resorbed by
      unfractionated bone cells very potently. FGF-2 (>/=10(-12) m) also increased
      cathepsin K and MMP-9 mRNA levels in mouse and rabbit osteoclasts. Among FGF
      receptors (FGFR1 to 4) only FGFR1 was detected on isolated mouse osteoclasts,
      whereas all FGFRs were identified on mouse osteoblasts. FGF-2 (>/=10(-12) m) up
      regulated the phosphorylation of cellular proteins, including p42/p44 mitogen
      activated protein (MAP) kinase, and increased the kinase activity of
      immunoprecipitated FGFR1 in mouse osteoclasts. The stimulation of FGF-2 on mouse
      and rabbit osteoclast functions was abrogated by PD-98059, a specific inhibitor
      of p42/p44 MAP kinase. These results strongly suggest that FGF-2 acts directly on
      mature osteoclasts through activation of FGFR1 and p42/p44 MAP kinase, causing
      the stimulation of bone resorption at physiological or pathological
      concentrations.

PMID- 10896950
TI  - Glucocorticoid-mediated destabilization of cyclin D3 mRNA involves RNA-protein
      interactions in the 3'-untranslated region of the mRNA.
AB  - Glucocorticoids regulate the expression of the G(1) progression factor, cyclin
      D3. Cyclin D3 messenger RNA (CcnD3 mRNA) stability decreases rapidly when murine
      T lymphoma cells are treated with the synthetic glucocorticoid dexamethasone.
      Basal stability of CcnD3 mRNA is regulated by sequences within the 3'
      untranslated region (3'-UTR). RNA-protein interactions occurring within the CcnD3
      3'-UTR have been analyzed by RNA electrophoretic mobility shift assay. Three
      sites of RNA-protein interaction have been mapped using this approach. These
      elements include three pyrimidine-rich domains of 25, 26, and 37 nucleotides.
      When the cyclin D3 3'-UTR was stably overexpressed, the endogenous CcnD3 mRNA was
      no longer regulated by dexamethasone. Likewise, overexpression of a 215
      nucleotide transgene that contains the 26- and 37-nucleotide elements blocks
      glucocorticoid inhibition of CcnD3 mRNA expression. These observations suggest
      that the 215-nucleotide 3'-UTR element may act as a molecular decoy, competing
      for proteins that bind to the endogenous transcript and thereby attenuating
      glucocorticoid responsiveness. UV-cross-linking experiments showed that two
      proteins of approximate molecular weight 37,000 and 52,000 bind to this 3'-UTR
      element.

PMID- 10896951
TI  - Domain swapping in human alpha A and alpha B crystallins affects oligomerization
      and enhances chaperone-like activity.
AB  - alphaA and alphaB crystallins, members of the small heat shock protein family,
      prevent aggregation of proteins by their chaperone-like activity. These two
      proteins, although very homologous, particularly in the C-terminal region, which
      contains the highly conserved "alpha-crystallin domain," show differences in
      their protective ability toward aggregation-prone target proteins. In order to
      investigate the differences between alphaA and alphaB crystallins, we engineered
      two chimeric proteins, alphaANBC and alphaBNAC, by swapping the N-terminal
      domains of alphaA and alphaB crystallins. The chimeras were cloned and expressed
      in Escherichia coli. The purified recombinant wild-type and chimeric proteins
      were characterized by fluorescence and circular dichroism spectroscopy and gel
      permeation chromatography to study the changes in secondary, tertiary, and
      quaternary structure. Circular dichroism studies show structural changes in the
      chimeric proteins. alphaBNAC binds more 8-anilinonaphthalene-1-sulfonic acid than
      the alphaANBC and the wild-type proteins, indicating increased accessible
      hydrophobic regions. The oligomeric state of alphaANBC is comparable to wild-type
      alphaB homoaggregate. However, there is a large increase in the oligomer size of
      the alphaBNAC chimera. Interestingly, swapping domains results in complete loss
      of chaperone-like activity of alphaANBC, whereas alphaBNAC shows severalfold
      increase in its protective ability. Our findings show the importance of the N-
      and C-terminal domains of alphaA and alphaB crystallins in subunit
      oligomerization and chaperone-like activity. Domain swapping results in an
      engineered protein with significantly enhanced chaperone-like activity.

PMID- 10896952
TI  - Down-regulation of T cell activation following inhibition of dipeptidyl peptidase
      IV/CD26 by the N-terminal part of the thromboxane A2 receptor.
AB  - Using synthetic inhibitors, it has been shown that the ectopeptidase dipeptidyl
      peptidase IV (DP IV) (CD26) plays an important role in the activation and
      proliferation of T lymphocytes. The human immunodeficiency virus-1 Tat protein,
      as well as the N-terminal nonapeptide Tat(1-9) and other peptides containing the
      N-terminal sequence XXP, also inhibit DP IV and therefore T cell activation.
      Studying the effect of amino acid exchanges in the N-terminal three positions of
      the Tat(1-9) sequence, we found that tryptophan in position 2 strongly improves
      DP IV inhibition. NMR spectroscopy and molecular modeling show that the effect of
      Trp(2)-Tat(1-9) could not be explained by significant alterations in the backbone
      structure and suggest that tryptophan enters favorable interactions with DP IV.
      Data base searches revealed the thromboxane A2 receptor (TXA2-R) as a membrane
      protein extracellularly exposing N-terminal MWP. TXA2-R is expressed within the
      immune system on antigen-presenting cells, namely monocytes. The N-terminal
      nonapeptide of TXA2-R, TXA2-R(1-9), inhibits DP IV and DNA synthesis and IL-2
      production of tetanus toxoid-stimulated peripheral blood mononuclear cells.
      Moreover, TXA2-R(1-9) induces the production of the immunosuppressive cytokine
      transforming growth factor-beta1. These data suggest that the N-terminal part of
      TXA2-R is an endogenous inhibitory ligand of DP IV and may modulate T cell
      activation via DP IV/CD26 inhibition.

PMID- 10896953
TI  - Extreme halophiles synthesize betaine from glycine by methylation.
AB  - Glycine betaine is a compatible solute, which is able to restore and maintain
      osmotic balance of living cells. It is synthesized and accumulated in response to
      abiotic stress. Betaine acts also as a methyl group donor and has a number of
      important applications including its use as a feed additive. The known
      biosynthetic pathways of betaine are universal and very well characterized. A
      number of enzymes catalyzing the two-step oxidation of choline to betaine have
      been isolated. In this work we have studied a novel betaine biosynthetic pathway
      in two phylogenically distant extreme halophiles, Actinopolyspora halophila and
      Ectothiorhodospira halochloris. We have identified a three-step series of
      methylation reactions from glycine to betaine, which is catalyzed by two
      methyltransferases, glycine sarcosine methyltransferase and sarcosine
      dimethylglycine methyltransferase, with partially overlapping substrate
      specificity. The methyltransferases from the two organisms show high sequence
      homology. E. halochloris methyltransferase genes were successfully expressed in
      Escherichia coli, and betaine accumulation and improved salt tolerance were
      demonstrated.

PMID- 10896954
TI  - The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional
      diversity of GIT2 through alternative splicing.
AB  - We recently characterized a novel protein, GIT1, that interacts with G protein
      coupled receptor kinases and possesses ADP-ribosylation factor (ARF) GTPase
      activating protein activity. A second ubiquitously expressed member of the GIT
      protein family, GIT2, has been identified in data base searches. GIT2 undergoes
      extensive alternative splicing and exists in at least 10 and potentially as many
      as 33 distinct forms. The longest form of GIT2 is colinear with GIT1 and shares
      the same domain structure, whereas one major splice variant prominent in immune
      tissues completely lacks the carboxyl-terminal domain. The other 32 potential
      variants arise from the independent alternative splicing of five internal regions
      in the center of the molecule but share both the amino-terminal ARF GTPase
      activating protein domain and carboxyl-terminal domain. Both the long and short
      carboxyl-terminal variants of GIT2 are active as GTPase-activating proteins for
      ARF1, and both also interact with G protein-coupled receptor kinase 2 and with
      p21-activated kinase-interacting exchange factors complexed with p21-activated
      kinase but not with paxillin. Cellular overexpression of the longest variant of
      GIT2 leads to inhibition of beta(2)-adrenergic receptor sequestration, whereas
      the shortest splice variant appears inactive. Although GIT2 shares many
      properties with GIT1, it also exhibits both structural and functional diversity
      due to tissue-specific alternative splicing.

PMID- 10896955
TI  - COPE guidelines on good publication practice. Committee on Publication Ethics.

PMID- 10896956
TI  - Committee on Publication Ethics: the COPE report 1999. Guidelines on good
      publication practice.

PMID- 10896958
TI  - How is sex considered in recent epidemiological publications on occupational
      risks?
AB  - OBJECTIVES: Although women account for almost half the working population in
      industrialised countries, a sex bias persists in publications on medical research
      in general and occupational health in particular. The objective was to review
      recent publications on how sex is considered in epidemiological studies of
      occupational health, and to answer the following questions: are men and women
      studied equally, what are the respective characteristics of the studies which
      comprise only men, only women, and both, and what strategy of data analysis is
      chosen by the authors to take account of the sex factor in mixed studies.
      MATERIALS: This review was based on publications in six journals during the year
      1997, and included all the original articles reporting an epidemiological study
      of occupational health. RESULTS: In all, 348 articles were reviewed. In 40
      articles (11%), the sex of the study population was not specified. In 177
      articles (51%), the study population was mixed. In 108 (31%), the population
      consisted exclusively of men, and in only 23 (7%), exclusively of women. Even
      when study populations were mixed, they included fewer women than men. The sex
      composition of the population was related to the occupational risk factor
      considered, and also to health outcome. Industrial sector workers, and exposure
      to chemicals were more likely to be studied in samples of men. Mortality and
      health outcomes such as neoplasms and cardiovascular diseases were also more
      often studied among men. Surprisingly, study design differed significantly
      according to the sex of the population, and prospective studies, cohort studies,
      and exposed versus non-exposed studies were more often carried out in samples of
      men. Among the 177 mixed studies, sex was not investigated in over a quarter
      (27%). In 26 articles (15%), sex was not taken into account, but the authors
      attempted to justify this decision. In 46 mixed studies (26%), the results were
      adjusted for sex, and in 46 (26%), the authors gave separate results for men and
      women. In 11 studies (6%), more complete strategies of data analysis were chosen,
      including research for interactions or adjustment, followed by stratification.
      CONCLUSION: This review of recent publications in occupational health
      epidemiology showed that women are still less often studied than men, and that
      the sex factor is not investigated in many mixed studies. The results therefore
      underline the need for further research on occupational hazards among women, and
      on sex differences.

PMID- 10896957
TI  - Modern approaches to blood pressure measurement.
AB  - BACKGROUND: Blood pressure (BP) is usually measured by conventional
      sphygmomanometry. Although apparently simple, this procedure is fraught with many
      potential sources of error. This review focuses on two alternative techniques of
      BP measurement: ambulatory monitoring and self measurement. REVIEW: BP values
      obtained by ambulatory monitoring or self measurement are characterised by high
      reproducibility, are not subject to digit preference or observer bias, and
      minimise the transient rise of the blood pressure in response to the surroundings
      of the clinic or the presence of the observer, the so called white coat effect.
      For ambulatory monitoring, the upper limits of systolic/diastolic normotension in
      adults include 130/80 mm Hg for the 24 hour BP and 135/85 and 120/70 mm Hg for
      the daytime BP and night time BP, respectively. For the the self measured BP
      these thresholds include 135/85 mm Hg. Automated BP measurement is most useful to
      identify patients with white coat hypertension. Whether or not white coat
      hypertension predisposes to sustained hypertension remains debated. However,
      outcome is better correlated with the ambulatory BP than with the conventional
      BP. In patients with white coat hypertension, antihypertensive drugs lower the BP
      in the clinic, but not the ambulatory BP, and also do not improve prognosis.
      Ambulatory BP monitoring is also better than conventional BP measurement in
      assessing the effects of treatment. Ambulatory BP monitoring is necessary to
      diagnose nocturnal hypertension and is especially indicated in patients with
      borderline hypertension, elderly patients, pregnant women, patients with
      treatment resistant hypertension, and also in patients with symptoms suggestive
      of hypotension. CONCLUSIONS: The newer techniques of BP measurement are now well
      established in clinical research, for diagnosis in clinical practice, and will
      increasingly make their appearance in occupational and environmental medicine.

PMID- 10896959
TI  - Musculoskeletal disorders of the neck and shoulders in female sewing machine
      operators: prevalence, incidence, and prognosis.
AB  - OBJECTIVES: To assess the occurrence and persistence of two restrictively defined
      neck-shoulder disorders among sewing machine operators. To assess factors
      associated with the development of neck-shoulder disorder and prognostic factors
      for remaining a case, when disorders were already present. METHODS: In an initial
      group of 243 sewing machine operators, 178 were followed up for 2 years. At
      baseline and at 1 and 2 years follow up the participants underwent a clinical
      examination of the neck and arms and filled in a questionnaire about current
      musculoskeletal complaints. Clinical criteria for two main neck-shoulder
      disorders were defined: rotator cuff tendinitis and myofascial pain syndrome. A
      baseline control group consisted of 357 women with varied non-repetitive work.
      RESULTS: At baseline the overall prevalence of myofascial pain syndrome and
      rotator cuff tendinitis was 15.2% and 5.8% among sewing machine operators
      compared with 9.0% and 2.2%, respectively, among controls. The presence of the
      disorders was strongly associated with a self perception of poor general health.
      Although myofascial pain syndrome showed a U shaped association with years as a
      sewing machine operator, rotator cuff tendinitis was absent among the newest
      recruits and present among 15% of the women with more than 20 years as a sewing
      machine operator. Besides years as a sewing machine operator, the risk of having
      a neck-shoulder disorder at baseline was significantly associated with high
      stress (prevalence ratio (PR)=2.54; 95% confidence interval (95% CI) 1.28 to
      5.05) when adjusted for age, body mass index, smoking, living alone with
      children, job strain, and social support from colleagues and supervisors. Only
      one of 13 participants with rotator cuff tendinitis at baseline recovered during
      follow up. Myofascial pain syndrome showed a much more fluctuating tendency. Low
      social support (RR 3.72; 95% CI 1.22 to 11.30) and smoking (RR 3.93; 95% CI 1.33
      to 11.58) were associated with the development of neck-shoulder disorders, which
      was also associated with neck-shoulder pain score and living alone with children.
      CONCLUSION: Rotator cuff tendinitis showed a higher degree of persistence than
      myofascial pain syndrome. Both disorders highly influenced the perception of
      general health. Women who lived alone with children, were smokers, or experienced
      low support from colleagues and supervisors had a higher risk of contracting a
      neck-shoulder disorder.

PMID- 10896960
TI  - Determinants of bone and blood lead concentrations in the early postpartum
      period.
AB  - OBJECTIVE: This study investigated determinants of bone and blood lead
      concentrations in 430 lactating Mexican women during the early postpartum period
      and the contribution of bone lead to blood lead. METHODS: Maternal venous lead
      was measured at delivery and postpartum, and bone lead concentrations, measured
      with in vivo K-x ray fluorescence, were measured post partum. Data on
      environmental exposure, demographic characteristics, and maternal factors related
      to exposure to lead were collected by questionnaire. Linear regression was used
      to examine the relations between bone and blood lead, demographics, and
      environmental exposure variables. RESULTS: Mean (SD) blood, tibial, and patellar
      lead concentrations were 9.5 (4.5) microg/dl, 10.2 (10.1) microg Pb/g bone
      mineral, and 15.2 (15.1) microg Pb/g bone mineral respectively. These values are
      considerably higher than values for women in the United States. Older age, the
      cumulative use of lead glazed pottery, and higher proportion of life spent in
      Mexico City were powerful predictors of higher bone lead concentrations. Use of
      lead glazed ceramics to cook food in the past week and increased patellar lead
      concentrations were significant predictors of increased blood lead. Patellar lead
      concentrations explained one third of the variance accounted for by the final
      blood lead model. Women in the 90th percentile for patella lead had an
      untransformed predicted mean blood lead concentration 3.6 microg/dl higher than
      those in the 10th percentile. CONCLUSIONS: This study identified the use of lead
      glazed ceramics as a major source of cumulative exposure to lead, as reflected by
      bone lead concentrations, as well as current exposure, reflected by blood lead,
      in Mexico. A higher proportion of life spent in Mexico City, a proxy for exposure
      to leaded gasoline emissions, was identified as the other major source of
      cumulative lead exposure. The influence of bone lead on blood lead coupled with
      the long half life of lead in bone has implications for other populations and
      suggests that bone stores may pose a threat to women of reproductive age long
      after exposure has declined.

PMID- 10896961
TI  - Is it feasible to construct a community profile of exposure to industrial air
      pollution?
AB  - OBJECTIVE: An epidemiological investigation to assess the validity of residential
      proximity to industry as a measure of community exposure. METHODS: 19 Housing
      estates in Teesside (population 1991: 77 330) in north east England were grouped
      into zones: A=near; B=intermediate; C=further from industry. With residential
      proximity of socioeconomically matched populations as a starting point a
      historical land use survey, historical air quality reports, air quality
      monitoring, dispersion modelling data, and questionnaire data, were examined.
      RESULTS: The populations in zones A, B, and C were similar for socioeconomic
      indicators and smoking history. Areas currently closest to industry had also been
      closest for most of the 20th century. Historical reports highlighted the
      influence of industrial emissions to local air quality, but it was difficult to
      follow spatial pollution patterns over time. Whereas contemporary NO(x) and
      benzene concentrations showed no geographical variation, dispersion modelling of
      emissions (116 industrial stacks, traffic, and domestic sources) showed a
      gradient associated with industry. The presumed exposure gradient of areas by
      proximity to industry (A>B>C) was evident for all of zone A and most of zones B
      and C. CONCLUSIONS: It was feasible to assemble a picture of community exposure
      by integration of measurements from different sources. Proximity of residence was
      a reasonable surrogate for complex community exposure.

PMID- 10896962
TI  - Longest held occupation in a lifetime and risk of disability in activities of
      daily living.
AB  - OBJECTIVES: To examine the association between the longest held occupation in a
      lifetime and risk of disability in activities of daily living (ADL) among elderly
      people (65 years and older) in northern Taiwan. METHODS: A case-control design
      was used nested within two cohorts of a total of 2198 elderly people who had been
      followed up either between 1993 and 1997 or between 1996 and 1997. Cases were 360
      elderly people with ADL disability within the study period. For each case, two
      sex matched controls were randomly sampled from the pool of elderly people free
      from ADL disability. Occupational data were collected through interviews
      conducted in 1997. Performed job contents were classified into occupational
      categories and occupation based social classes. Unconditional logistic regression
      techniques were used to estimate relative risk and 95% confidence intervals (95%
      CIs) of ADL disability. RESULTS: Compared with people who were former
      legislators, government administrators, or business executives and managers,
      workers in agriculture, animal husbandry, forestry, or fishing (odds ratio (OR)
      1.9, 95% CI 1.1 to 3.5) and workers in craft and related trades (OR 1.9, 95% CI
      1.1 to 3.4) had significantly increased risks of subsequent ADL disability.
      Differential risks of ADL disability were found across social classes, with a
      significant dose-response trend in which unskilled blue collar workers had an 1.8
      times higher risk of ADL disability than higher social classes of white collar
      workers. CONCLUSIONS: After adjustment for education, there was still an inverse
      relation between risk of ADL disability and social class. Although total control
      for all the known risk factors for ADL disability among elderly people was
      impossible, the results tend to suggest a potential for an effect of longest held
      occupation in a lifetime on risk of ADL disability.

PMID- 10896963
TI  - Non-fatal work related injuries in a cohort of Brazilian steelworkers.
AB  - OBJECTIVES: Workers in the steel industry are exposed to various severe hazards.
      This study investigated risk factors for non-fatal injury occurring in the
      workplace and during travel to and from work in steelworkers in Brazil. METHODS:
      Non-fatal work related injuries during employment from January 1977 to September
      1992 were analysed in a cohort of 21 732 male workers in the steel plant of
      USIMINAS, Brazil. RESULTS: There were 14 972 non-fatal injuries during follow up,
      with 10 891 injuries in the workplace and 4081 during travel to and from work
      (travel to work injury). The rate of injury in the workplace was 5.6/100 person
      years and that of travel to work injury was 2.1/100 person-years. The most common
      injuries were to hands, arms, and eyes, with 90% of the eye injuries caused by a
      foreign body. Both rates of workplace and travel to work injury increased
      significantly with the number of injuries previously experienced, and decreased
      with number of years in employment and calendar period. The rates of travel to
      work injury also seemed to decrease with age, but age was not an independent
      predictor of workplace injury when we controlled for duration of employment. The
      rate of workplace injury was increased eightfold for workers who had experienced
      more than six previous injuries compared with those with no previous workplace
      injuries after adjusting for duration of employment and calendar period.
      Labourers were most at risk of workplace injury, with about eight injuries per
      100 person-years. Travel to work injury was most common among support workers,
      with nearly half of the travel to work injuries affecting the eyes. CONCLUSION:
      The rate of injury was high in these steelworks, both for workplace and travel to
      work injuries. Characteristics of the work areas and the employees can identify
      high risk groups; protective measures, safety, health training, and injury
      programmes should concentrate particularly on these groups. Prevention of eye
      injury needs special attention in steelworks.

PMID- 10896964
TI  - Risk of mesothelioma from exposure to crocidolite asbestos: a 1995 update of a
      South African mortality study.
AB  - OBJECTIVE: To find the risk of developing mesothelioma in a cohort born in 1916
      36 in Prieska, Northern Cape Province, South Africa. METHODS: A birth cohort
      mortality study was carried out in a small town in the Northern Cape Province,
      South Africa, with a history of crocidolite asbestos mining and milling. The
      cohort comprised all white births registered in the magisterial district of
      Prieska from 1916 to 1936, inclusive (2390). Causes of death due to mesothelioma
      and other cancers as recorded on medical certificates of cause of death were
      investigated. Person-years analysis was used to calculate mortalities due to
      mesothelioma, other respiratory cancers, and other non-respiratory cancers.
      Proportional cancer mortalities were also calculated for mesothelioma and other
      specific neoplasms. RESULTS: The follow up rate for the cohort was 74.3% in 1995,
      and 683 traced members (38.6%) had died. Cause of death was unknown for 6.4% of
      deaths. There were 118 cases of cancer, 28 of them from mesothelioma, giving a
      cause specific mortality for mesothelioma of 277 (170-384) per 10(6) person
      years. The rates for men and women were 366 and 172 per 10(6) person-years,
      respectively. The mortality for lung cancer (29 deaths) was 287 (135-436) per
      10(6) person-years, and that for other non-respiratory cancers (60 deaths) was
      593 (442-745). Two cases of laryngeal and four of colon cancer were observed. All
      cancer mortality, mesothelioma, and lung cancer proportional cancer mortality
      ratios were increased. CONCLUSION: The mortality for mesothelioma in men was
      twice that in women, probably because men were more likely to have had both
      occupational and environmental exposure to asbestos. Nevertheless, the mortality
      in women was still high and is probably indicative of the environmental exposure
      as white women were rarely employed in the asbestos industry in the Prieska area.
      Due to the long latency from first exposure to diagnosis of the neoplasm, the
      cause specific mortality in this cohort could be expected to increase rapidly
      over the next 10 years.

PMID- 10896965
TI  - Lung cancer mortality in a site producing hard metals.
AB  - OBJECTIVES: To study the mortality from lung cancer from exposures to hard metal
      dust at an industrial site producing hard metals--pseudoalloys of cobalt and
      tungsten carbide--and other metallurgical products many of which contain cobalt.
      METHODS: A historical cohort was set up of all subjects who had worked for at
      least 3 months on the site since its opening date in the late 1940s. A full job
      history could be obtained for 95% of the subjects. The cohort was followed up
      from January 1968 to December 1992. The exposure was assessed by an industry
      specific job exposure matrix (JEM) characterising exposure to hard metal dust
      from 1 to 9 and other possibly carcinogenic exposures as present or absent.
      Smoking information was obtained by interview of former workers. Standard
      lifetable methods and Poisson regression were used for the statistical analysis
      of the data. RESULTS: Mortality from all causes was close to the expected
      (standardised mortality ratio (SMR) 1.02, 399 deaths) whereas mortality from lung
      cancer was significantly increased among men (SMR 1.70; 46 deaths, 95% confidence
      interval (95% CI) 1.24 to 2.26). By workshop, lung cancer mortality was
      significantly higher than expected in hard metal production before sintering (SMR
      2.42; nine deaths; 95%CI 1.10 to 4.59) and among maintenance workers (SMR 2.56;
      11 deaths; 95%CI 1.28 to 4.59), whereas after sintering the SMR was lower (SMR
      1.28; five deaths; 95%CI 0.41 to 2.98). The SMR for all exposures to hard metal
      dust at a level >1 in the JEM was in significant excess (SMR 2.02; 26 deaths;
      95%CI 1.32 to 2.96). The risks increased with exposure scores, duration of
      exposure, and cumulative dose reaching significance for duration of exposure to
      hard metal dust before sintering, after adjustment for smoking and known or
      suspected carcinogens. CONCLUSION: Excess mortality from lung cancer was found
      among hard metal production workers which cannot be attributed to smoking alone.
      This excess occurred mostly in subjects exposed to unsintered hard metal dust.

PMID- 10896966
TI  - Cohort mortality and cancer incidence survey of recent entrants (1982-91) to the
      United Kingdom rubber industry: preliminary findings.
AB  - OBJECTIVES: To monitor the occurrence of stomach and lung cancer in a newly
      defined cohort of United Kingdom rubber workers and to report findings for other
      cancers in an early period of follow up. METHODS: A prospective cohort of 9031
      male and female workers from 42 United Kingdom rubber factories has been
      enumerated. All employees had a minimum of 12 months employment and were first
      employed at one of the participating factories in the period 1982-91. Mortality
      data were available for the period 1983-98 and cancer registration data for the
      period 1983-94. The mortality and cancer incidence experienced by the cohort were
      compared with expected values based on national rates defined by period, age, and
      sex. RESULTS: Mortality from lung cancer was close to expectation (men: observed
      (obs) 11, expected (exp) 12.70, standardised mortality ratio (SMR) 87, 95%
      confidence interval (95% CI) 43 to 155; women: obs 0, exp 1.34, SMR 0, 95% CI 0
      to 275). Mortality from stomach cancer was unexceptional (men: obs 1, exp 2.69,
      SMR 37, 95% CI 1 to 207; women: obs 0, exp 0.24, SMR 0, 95% CI 0 to 1537). Many
      statistical comparisons were made both for mortality data and for cancer
      registration data; only one difference between observed and expected numbers was
      significant (mortality from cancer of the testis: obs 3 exp 0.51, SMR 589, 95% CI
      122 to 1722). Corresponding findings for incident cancers of the testis were
      unexceptional (obs 5, exp 5.13, standardised registration ratio (SRR) 97, 95% CI
      32 to 227). CONCLUSION: The findings should be treated with caution as they
      relate to an early period of follow up. Nevertheless, they hold out the prospect
      that the increased SMRs for stomach and lung cancers reported for historical
      cohorts of United Kingdom rubber workers may not be apparent in more recent
      cohorts.

PMID- 10896967
TI  - Interruption of prophylaxis for major opportunistic infections in HIV-infected
      patients receiving triple combination antiretroviral therapy.
AB  - Interruption of prophylaxis for major opportunistic infections in HIV-infected
      patients receiving triple combination antiretroviral therapy. OBJECTIVE: To
      determine whether HIV-infected patients receiving highly active antiretroviral
      therapy (HAART) and recovering a CD4 cell number above 200x10(6)/l may safely
      discontinue primary and secondary prophylaxes for major opportunistic infections.
      DESIGN: Retrospective study of a single-center, prospectively constituted cohort
      of 223 patients receiving HAART with a protease inhibitor, of whom 137 received
      at least one prophylaxis. METHODS: Exhaustive informations on prophylaxis use,
      clinical and laboratory data were used to produce descriptive statistics on
      infectious events, duration of HIV infection, time on HAART, time to prophylaxis
      interruption, length of follow-up and biological values at relevant time points.
      RESULTS: Fifty-one patients with a history of severe immunodepression (median CD4
      nadir: 62x10(6)/l), including 16 patients with CDC stage C infection,
      discontinued at least one prophylaxis. Primary or secondary P. carinii pneumonia
      prophylaxis was discontinued in 43 patients: 1 first episode of PCP occurred
      after 2 months but no other episode was recorded after a median follow-up of 16
      months. Toxoplasmosis primary or secondary prophylaxis, secondary cytomegalovirus
      prophylaxis and primary or secondary M. avium complex prophylaxes were
      discontinued in respectively 37, 5 and 5 patients, and no event was recorded
      after respective follow-ups of 16, 7 and 15 months. Nine secondary and 2 primary
      acyclovir prophylaxes were discontinued, and two events were observed after 1 and
      19 months; no other event was noted after a follow-up of 22 months. CONCLUSION:
      Prophylaxis for opportunistic infections could be safely interrupted in most of
      these severely immunodeficient patients recovering a CD4 cell count above
      200x10(6)/l on HAART. This confirms the efficiency of immune restoration and is
      beneficial to patients but, since 3 infectious events were recorded, caution
      should be taken before making a decision based on immunological and virological
      considerations.

PMID- 10896968
TI  - [Hyperferritinemia].
AB  - Many causes provoke elevated serum ferritin levels including not only iron
      overload, but also many pathological situations where hyperferritinemia or
      modified isoferritin profiles have no direct relationship with body iron stores.
      There are five general categories of hyperferritinemia: hemochromatosis,
      inflammatory syndromes, cytolysis, hemophagocytosis, Still's disease, and other
      etiologies.

PMID- 10896969
TI  - [Antineutrophil cytoplasm antibodies (ANCA): description and immunopathological
      role].
AB  - These antibodies are specific for antigens in the cytoplasm of neutrophils. The
      main antigenic targets are proteinase 3(PR3) and myeloperoxydase (MPO) but other
      targets have been described without determinant conclusions for clinical
      practice. Staining patterns can be distinguished by an indirect
      immunofluorescence test (IFI), in which ethanol fixed neutrophils from healthy
      donors are incubated with patient's sera. Two patterns are distinguished:
      cytoplasmic pattern (c-ANCA) and perinuclear pattern (p-ANCA). When ANCA are
      detected by IFI, from a practical point of view, anti -MPO and anti-PR3
      antibodies are tested. ANCA have been strongly associated with a spectrum of
      necrotizing small vessel vasculitides that includes Wegener's granulomatosis,
      microscopic polyangiitis, Churg and Strauss syndrome, pauci-immune focal
      necrotizing and crescentic glomerulonephritis. ANCA are a diagnosic marker and
      useful for the follow-up of the patients. ANCA can be observed in other
      pathologies: rhumatismal autoimmune diseases, inflammatory gut diseases, after
      drugs (hydralazine, minocycline, propylthiouracil), after silical exposition,
      infections (cystic fibrosis, endocarditis, HIV infection). The specificity is
      different and rarely anti-MPO. The ANCA role for the development of vasculitis is
      not completely elucidated. Some arguments are against a primary role of ANCA in
      the development of vasculitis. Certainly, amplification role for neutrophil
      activation is demonstrated but the primary event responsible of neutrophil
      activation is not yet defined.

PMID- 10896970
TI  - [Polyarteritis nodosa: clinical, prognostic and therapeutic features].

PMID- 10896971
TI  - [Microscopic polyangiitis].
AB  - Microscopic polyangiitis is a non-granulomatous necrotizing vasculitis involving
      small vessels. Clinical manifestations are highly polymorphic, but rapidly
      progressive glomerulonephritis is one of the most frequent and most severe
      manifestations of the disease. Biopsy of an affected organ and detection of
      circulating anti-neutrophil cytoplasmic antibodies (ANCA) are key elements for
      the positive diagnosis of microscopic polyangiitis. Biopsies can disclose
      necrotizing vasculitis affecting small vessels, without granulomas and without
      immune deposits. ANCA are very specific for microscopic polyangiitis, Wegener's
      granulomatosis and Churg-Strauss syndrome when they are positive by indirect
      immunofluorescence and are directed against myeloperoxidase or proteinase 3. Such
      ANCA are found in about 70% of patients with microscopic polyangiitis. Treatment
      of severe forms of microscopic polyangiitis is based on the administration of
      pulse methylprednisolone, oral corticosteroids and cyclophosphamide. In the
      mildest forms of the disease, one can probably try either to competely avoid
      using immunosuppressive drugs, or to replace cyclophosphamide with azathioprine.
      Treatment induces a complete remission of the disease in more than 90% of cases,
      but about 30% of the patients will experience a relapse, and progressive
      worsening of renal function can occur in patients with severe chronic renal
      failure.

PMID- 10896972
TI  - How to optimize the treatment of systemic vasculitides.

PMID- 10896973
TI  - [Prevention of deep venous thrombosis in medical patients].
AB  - Prophylaxis of deep vein thrombosis with standard heparin and low molecular
      weight heparin has been studied in many clinical trials in surgical patients and
      in few and various medical conditions in hospitalized subjects. Clinical trials
      have been conducted in patients with recent myocardial infarction, heart failure,
      stroke, pulmonary sepsis, cancer, or any acute disease with a high risk factors
      for deep vein thrombosis (previous thromboembolism, thrombophilia, obesity,
      recent bedridden, dehydratation.). The combination of a high risk disease with a
      high risk factor related to the history of the patient might reasonably conduct
      to a prophylaxis with low molecular weight heparins. The duration of this
      treatment has to be short and limited to the period of the acute medical
      condition inducing a high risk for deep vein thrombosis. Prophylaxis has to be
      offered to patients with ischemic stroke, cardiac failure, recent myocardial
      infarction, active cancer or any other acute medical disease in patients with a
      previous thromboembolism or thrombophilia history. Bedridden status and age are
      not, by themselves, an indication for prophylaxis with heparins. A widespread
      diffusion of these recommendations is needed to reduce overprescriptions.

PMID- 10896974
TI  - [Neoadjuvant chemotherapy in the treatment of breast cancer].

PMID- 10896975
TI  - [Critical analysis of the causal role of human papillomavirus in cutaneomucosal
      oncology].

PMID- 10896976
TI  - [Acquired amegakaryocytic thrombocytopenic purpura treated with intravenous
      immunoglobulins].
AB  - Acquired amegakaryocytic thrombocytopenic purpura is a rare disorder
      characterized by severe thrombocytopenia due to the absence of bone marrow
      megakaryocytes. The pathogenic mechanisms of this disorder have not well defined;
      consequently, several empirical therapies are used. We reported the case of a 38
      year-old mean who was hospitalized for serious bleeding syndrome. The platelet
      count was 10 yen10(9)/L. The bone marrow aspirate and biopsy showed the absence
      of megakaryocytes but otherwise normal granulocyte and erythroid precursors. No
      definable etiology has been found. After the unsuccessful use of prednisone,
      intravenous immunoglobulin therapy was started and resulted in favorable reponse.

PMID- 10896977
TI  - [Aspirin-induced angioedema of the nape of the neck with naproxen cross-reaction:
      a case report].
AB  - We report a case of angioedema limited to the nape of the neck. The symptoms
      occurred every morning for fifteen days, two or three hours after taking aspirin.
      The patient took salicylic acid, 100mg per day, orally for two years. The
      angioedema occurred alone, without urticaria. When aspirin was stopped, the
      symptoms disappeared. A few weeks later, the patient took napoxen, with
      occurrence of more pronounced symptoms. The causality score was I3 for both
      drugs. The most common side-effects of aspirin intake are asthma and
      urticaria/angioedema. The mechanism of this hypersensitivity is unknown. There
      are numerous cross-reactions between aspirin and other NSAIDs. This case points
      out the importance of accurate history taking concerning self-medication for the
      diagnosis of angioedema.

PMID- 10896978
TI  - [Efficacy of fludarabine in the treatment of angioimmunoblastic lymphoma (AIL)].

PMID- 10896979
TI  - [Sarcoidosis-lymphoma syndrome with alternating outbreaks of the two illnesses].

PMID- 10896980
TI  - [Comments on the case reported by P. Corbi et al.: "Idiopathic aneurysm of the
      main pulmonary artery"].

PMID- 10896981
TI  - [In Process Citation]

PMID- 10896982
TI  - [Evolution of polyvalent intravenous immunoglobulins (IVIg) prescription, at the
      Assistance Publique - Hopitaux de Paris between 1988 and 1997. Results of the
      plan of action set up in order to regulate the prescription].
AB  - In 1991 the public hospitals in Paris set up a plan to regulate the prescription
      of IVIg. The plan includes an expert committee and reliable data collection. The
      expert committee has a threefold mission: i) perform an annual up-date of IVIg
      classification using three categories: accepted indications (group I), currently
      deabated indications (group II), and unwarranted indications (group III); ii)
      develop guidelines for improved therapeutic strategies; iii) stimulate research.
      Data on use of IVIg are collected in 16 pilot hospitals. These data designate
      IVIg prescriptions by indication. Data are centralized by the CEDIT which
      publishes an annual report. Between 1988 and 1991, prescription of IVIg increased
      at an average annual rate of 33%. Between 1991 and 1996, the amount of IVIg used
      leveled off: approximately 330 kilograms/year, excluding research protocols. In
      1997 there was a decline to 299 kilograms accounting for a total expenditure of
      44 million French francs (US$ 6.7M). In 1997, group I prescriptions represented
      80% of all IVIg prescriptions, group II 9.8% and group III 9.1%. Comparison of
      medical practice with a scientificaly recognised reference made it possible for
      AP-HP to set up an effective regulation of IVIg prescriptions. The longevity of
      this evaluation work is by itself a success.

PMID- 10896983
TI  - [Immunomodulatory effects of intravenous immunoglobulins].
AB  - Intravenous immunoglobulin (IVIg) has been used for many years in the treatment
      of primary and secondary antibody deficiencies. IVIg was first demonstrated to be
      effective in auto-immune desorders twenty years ago in the treatment of
      idiopathic thrombocytopenic purpura. The beneficial effect of IVIg has since been
      established in the Guillain-Barre syndrome, chronic inflammatory demenilating
      polyneuropathy, myasthenia gravis, dermatomyositis, Kawasaki syndrome and graft
      versus host disease. The beneficial effect of IVIg has been suggested in a large
      number of other auto-immune and systemic inflammatory conditions. The mode of
      action of IVIg is complex, involving Fc receptor blockade, interference with
      complement activation and the cytokine network, provision of anti-idiotypic
      antibodies and modulation of T and B cell activation and differentiation. Such a
      broad range of activities reflects the function of normal circulating
      immunoglobulins in maintaining tolerance to self in healthy individuals.

PMID- 10896984
TI  - [Treatment of chronic immune-mediated polyneuropathies. State of the art and
      perspectives].
AB  - Chronic immune-mediated polyneuropathies encompass chronic inflammatory
      demyelinating polyneuropathies, polyneuropathies associated with monoclonal
      gammopathy and multifocal motor neuropathy with persistent conduction blocks.
      Their diagnosis is made on clinical, electrophysiological and sometimes
      immunochemical and pathological criteria. The efficacy of short-term treatments
      (corticosteroids, plasma exchanges, intravenous immunoglobulins) depends on the
      type of the polyneuropathy, but these treatments may sometimes lead to prolonged
      improvement. The efficacy of long-term treatments needs further evaluation.

PMID- 10896985
TI  - [Modulation of experimental myasthenia gravis by IVIg].
AB  - Myasthenia Gravis (MG) is an autoimmune disease mediated by antibodies directed
      against the acetylcholine receptor (AChR). Treatment by IVIg is effective in
      acute forms of myasthenia gravis. In order to determine the in vivo effects of
      the various fractions of human immunoglobulins, we used an experimental model of
      myasthenia gravis in SCID mice. To this end, thymic cells from MG patients are
      transferred to these mice according to a well defined protocol. When establishing
      of the model, we noticed the appearance of anti-AChR antibodies and the loss of
      AChR expression at the muscle level. After treatment with IVIgG or IVIgM, the
      mice displayed a lower anti-AChR antibody titer compared to control mice (albumin
      treated) and the loss of the AChR number at the muscle was significantly reduced.
      These results obtained from one MG patient indicate that the human immunoglobulin
      preparations induce significant effects on pathogenic parameters in the SCID
      mouse model. Therefore this model is interesting to approach the mechanisms of
      action of human immunoglobulins and deserves further investigation.

PMID- 10896986
TI  - [Contribution of intravenous immunoglobulins to the treatment of myasthenia].
AB  - Myasthenia Gravis (MG) is an autoimmune disease characterized by the production
      of auto antibodies directed against the acetylcholine receptor of the neuro
      muscular synapse. The signs and symptoms are a muscular deficit involving the
      spinal or cranial muscles. The degree of weakness changes spontaneously over
      shorter or longer periods. Some exacerbations, called myasthenia crisis, involve
      the respiratory muscle and are life-threatening. The prognosis of these crisis
      has been transformed by the use of mechanical ventilation. Treatments directed on
      immune-regulation such as thymectomy, corticosteroids or immunossupressive drugs
      contribute to the improvement in functional status and reduce the risk of
      exacerbation. Plasma exchanges lead to a rapid improvement of weakness during
      exacerbations. They are, despite the lack of controlled study, the reference
      treatment for acute exacerbations. More recently, high doses of immunoglobulins
      have been proposed and a controlled study has shown that they could be an
      alternative for the treatment of acute exacerbations of MG. Indication of
      immunoglobulin in the long term management of MG is not established.

PMID- 10896987
TI  - [Guillain-Barre syndrome: epidemiological, clinical and therapeutic insight].
AB  - The average annual incidence of Guillain-Barre syndrome is 1.5 per 100 000.
      Mortality was about 5% in a recent clinical trial. Ten percent of patients have
      severe neurological sequelae one year after onset. For these patients, general
      care is essential and should be provided in appropriate hospital units.
      Corticosteroids, administered orally or intravenously are ineffective. Plasma
      exchange (PE) was the first treatment to demonstrate efficacy in randomized
      clinical trials. Indications have been recently specified. Patients who can walk
      must be given two PEs and two additional PEs in case of aggravation. Four plasma
      exchanges are sufficient in patients unable to walk unaided (intermediate form)
      or who are mechanically ventilated (severe form). No further PE is required if
      the patient fails to improve. High-dose intravenous immunoglobulins (0.4 g /kg
      daily for 5 days) and PE have equivalent efficacy in intermediate and severe
      forms. The optimal dose of IVIg and the number of Pes in the different severity
      forms are being assessed in an ongoing study.

PMID- 10896988
TI  - [Intravenous immunoglobulins (IVIg) in the treatment of multiple sclerosis].
AB  - Intravenously administered immunoglobulins (IVIg) have been used for the
      treatment of various autoimmune diseases. In multiple sclerosis (MS), recent
      studies point out the beneficial role of this treatment that reduces relapse rate
      and arrests disease progression in relapsing-remitting patients. In the present
      article, we summarize and interpret the clinical, immunological, and neuro
      radiological data related to IVIg treatment in MS. A synthesis between the
      information gathered will enable better understanding and treatment of this
      chronic disease.

PMID- 10896989
TI  - [Birdshot retinochoroidopathy].
AB  - Birdshot retinochoriodopathy is a bilateral posterior uveitis seen in adults over
      45 years of age. The uveitis is associated with moderate vitreal inflammation,
      vasculides of large vessels, chronic papillitis and the yellow birdshot spots
      typical of the disease. The disease shows tight linkages with HLA A29 carried by
      more than 90% of the patients. The visual prognosis depends on the development of
      complications of the chronic ocular inflammation, particularly crystoid macular
      edema. These complications lead to lowered visual acuity which becomes a major
      handicap. Long-term local or general corticosteroid therapy is required and leads
      to cortico-dependence. An immunosuppressor (cyclosporinA) may be associated. As
      these treatments cause major morbidity, intravenous immunoglobulins offer a less
      toxic therapeutic approach. Intravenous immunoglobulins can reduce inflammatory
      phenomena, providing an interesting alternative for the treatment of birdshot
      retinochoroidopathy.

PMID- 10896990
TI  - [Intravenous immunoglobulins in the treatment of polymyositis and
      dermatomyositis].
AB  - Polymyositis and dermatomyositis are two inflammatory muscle diseases of unknown
      origin mediated by a dysimmune mechanism via a cytotoxic effect against the
      muscle fiber in polymyositis and a humoral effect against the muscle vessels in
      dermatomyositis. First line treatment of polymyositis and dermatomyositis is
      still based on corticosteroid therapy. In case of failure, corticosteroid
      dependence, or intolerance, a second line treatment using immunosuppressors or
      polyvalent human intravenous immunoglobulins (IVIg) is usually associated. We
      report our experience with IVIg in the treatment of 50 patients with myositis
      unresponsive to corticosteroids and immunosuppressors. Thirty-five patients had
      polymyositis and 15 had dermatomyositis. We discuss the possible mechanisms and
      their precise role in the therapeutic armamentarium in these dysimmune diseases.

PMID- 10896991
TI  - [Therapeutic use of intravenous immunoglobulins in the antiphospholipid
      syndrome].
AB  - Although experience remains limited and uncontrolled, intravenous immunoglobulin
      (IVIg) therapy probably has a place in the management of selected patients with
      the antiphospholipid syndrome. It seems effective for the prevention of recurrent
      pregnancy losses when conventional strategies using subcutaneous heparin and low
      dose aspirin have failed. IVIg are currently investigated in the treatment of
      recurrent in vitro fertilization failure associated with antiphospholipid
      antibodies. In patients with severe thrombocytopenia, IVIg usually induce a
      prompt but transient remission. Finally, IVIg associated with steroids and
      heparin might improve survival in the rare but life-threatening catastrophic
      antiphospholipid syndrome.

PMID- 10896992
TI  - [Viral safety: European and French directives].
AB  - The viral safety of IVIg is defined by transposition of European Directives.
      Directive 89/381/CEE defines plasma-derived medicinal products (pd-MP) which
      should be registred through a Marketing Authorization (75/318/CEE) and requires
      specific criteria for donation acceptability and fractionation processing.
      Recommendations and Notes for Guidance are prepared by the "Biotechnology Working
      Party" (BWP), Committee for Proprietary Medicinal Products (CPMP) ad hoc group.
      "Note for Guidance on Virus Validation Studies: CPMP/BWP/268/95" defines, for
      conventional viruses, the validation study as regards viral elimination
      /inactivation steps (relevant virus, scale reduction system and statistical
      interpretation of the results). "Note for Guidance on 'blood products'-
      CPMP/BWP/269/95" defines the key issues of viral safety: starting material, viral
      elimination /inactivation steps within the fractionation processing and in
      process controls. Pd-MP used as excipients are also covered. BWP/CPMP recommends
      that exclusion criteria only be considered for sporadic, familial or iatrogenic
      Creutzfeldt-Jakob disease (CJD), while withdrawal should be undertaken, according
      to the precaution principle, when a donor is suffering from nv-CJD (February
      1998). Also, screening tests currently under development for transmissible
      spongiform encephalopathies are encouraged to be introduced for fractionation
      products (January 1999). Some donor exclusion criteria for conventional viruses
      and prions are specific to France. In conclusion, measures taken to ensure pd-MP
      viral safety are constantly changing. Its evaluation can only be done when
      considering numerous parameters within a global context.

PMID- 10896993
TI  - Comparative analysis of thyroid carcinoma in Germany and the U.S.

PMID- 10896994
TI  - Loss of fragile histidine triad gene expression is associated with progression of
      esophageal squamous cell carcinoma, but not with the patient's prognosis and
      smoking history.
AB  - BACKGROUND: Recently, fragile histidine triad (FHIT) gene abnormality has been
      thought to be associated with several malignancies and smoking history. The
      authors previously discovered that methylation of the 5' CpG island of the FHIT
      gene was closely associated with transcriptional inactivation in esophageal
      squamous cell carcinoma (SCC); however, the clinical impact of the FHIT gene in
      esophageal carcinoma is still unknown. METHODS: In this article, the authors
      evaluated the clinical impact of the FHIT gene in 149 esophageal squamous cell
      carcinoma (SCC) patients retrospectively using immunohistochemical analysis. They
      also examined the correlation between FHIT protein expression and smoking
      history. RESULTS: Among 149 curative resection (R0) cases of esophageal SCC,
      normal FHIT protein expression was noted in only 33 cases (22.1%), whereas
      reduced FHIT protein expression was noted in 67 cases and there was no FHIT
      expression in 50 cases. When a tumor invaded the muscle layer, FHIT protein
      expression was markedly reduced. The cases with reduction or loss of FHIT protein
      expression tended to have poor prognoses (P = 0.069). However, Cox multivariate
      analysis revealed that FHIT protein reduction had no relation to prognosis. FHIT
      protein expression had no relation to smoking history. CONCLUSIONS: FHIT protein
      expression was associated with progression of esophageal SCC, however, it may not
      be associated with the patient's prognosis and smoking history.

PMID- 10896995
TI  - Gastric lymphomas in Turkey. Analysis of prognostic factors with special emphasis
      on flow cytometric DNA content.
AB  - BACKGROUND: In contrast to DNA ploidy, to the authors' knowledge the prognostic
      significance of S-phase fraction (SPF) in gastric lymphomas has not been
      determined. In the current study, the prognostic significance of various
      parameters including SPF and DNA aneuploidy were analyzed and some distinct
      epidemiologic and biologic features of gastric lymphomas in Turkey were found.
      METHODS: A series of 78 gastric lymphoma patients followed at Hacettepe
      University is reported. DNA flow cytometry was performed for 34 patients. The
      influence of various parameters on survival was investigated with the log rank
      test. The Cox proportional hazards model was fitted to identify independent
      prognostic factors. RESULTS: The median age of the patients was 50 years. There
      was no correlation between patient age and tumor grade. DNA content analysis
      revealed 4 of the 34 cases to be aneuploid with DNA index values < 1.0. The mean
      SPF was 33.5%. In the univariate analysis, surgical resection of the tumor,
      modified Ann Arbor stage, performance status, response to first-line
      chemotherapy, lactate dehydrogenase (LDH) level, and SPF were important
      prognostic factors for disease free survival (DFS). The same parameters,
      excluding LDH level, were important for determining overall survival (OS). In the
      multivariate analysis, surgical resection of the tumor, disease stage,
      performance status, and age were found to be important prognostic factors for OS.
      CONCLUSIONS: To the authors' knowledge the current study is the first to
      demonstrate the prognostic significance of SPF in gastric lymphomas. The
      distinguishing features of Turkish gastric lymphoma patients are 1) DNA indices
      of aneuploid cases that all are < 1.0, which is a unique feature; 2) a lower
      percentage of aneuploid cases; 3) a higher SPF; 4) a younger age distribution;
      and 5) lack of an age-grade correlation. The authors conclude that gastric
      lymphomas in Turkey have distinct biologic and epidemiologic characteristics.

PMID- 10896996
TI  - Changes in P-glycoprotein expression in gastric carcinoma with respect to distant
      gastric mucosa may be influenced by p53.
AB  - BACKGROUND: The effectiveness of some chemotherapeutic agents used to treat
      gastric carcinoma patients may be impaired by the presence of P-glycoprotein (P
      gp) and the status of p53. A modulation of P-gp expression by p53 or other
      alterations during tumorigenesis have been reported. The authors analyzed P-gp
      expression in relation to p53 and histopathologic features in gastric carcinoma.
      METHODS: Forty-one resected gastric carcinomas and mucosa distant from the tumor
      were assessed for P-gp expression by immunohistochemistry with C494 and JSB-1
      antibodies. p53 expression was also immunohistochemically assessed by DO7
      antibody in tumor samples. P-gp and p53 expression were semiquantitatively
      analyzed according to the percentage of stained cells. Histologic type, grade,
      vessel invasion, and stage were also studied. RESULTS: Moderate or high P-gp
      expression was detected in gastric carcinoma in 29 cases (71%) and in gastric
      mucosa remote from the tumor in 36 cases (88%). This reduction in P-gp expression
      was observed in 22% of the carcinomas, all but 1 being p53 immunonegative tumors.
      Thus, 8 (42%) of the p53 immunonegative carcinomas showed a loss of P-gp
      expression compared with their distant gastric mucosa. All p53 immunopositive
      carcinomas coexpressed P-gp. No correlation between P-gp expression and
      histologic type, grade, vessel invasion, or stage was found. CONCLUSIONS: P-gp
      expression in gastric carcinomas is frequent and coexpression with p53 is found.
      The analysis of P-gp expression in carcinomas and distant mucosa show that it is
      not regulated by p53, but a loss of P-gp detected in some of these carcinomas is
      mainly associated with a lack of p53 protein accumulation.

PMID- 10896998
TI  - Tumor thickness is a histopathologic predictive parameter of tumor metastasis and
      prognosis in patients with Dukes stage C ulcerative-type colorectal carcinoma. A
      two-hospital-based study.
AB  - BACKGROUND: Metastasis to the liver or lymph nodes is an important prognostic
      factor in patients with colorectal carcinoma. The purpose of the current study
      was to estimate the power of tumor thickness in predicting metachronous liver
      metastasis (MLM), lymph node metastasis (LNM), or overall survival (OS) in
      patients at two hospitals (the National Cancer Center Hospital [NCCH] and the
      National Cancer Center Hospital East [NCCHE]) to confirm the reproducibility of
      the study. METHODS: The subjects of this study were 74 and 186 consecutive
      patients with ulcerative-type colorectal carcinoma treated at the NCCH and NCCHE,
      respectively. Tumor thickness was measured in three areas: 1) the marginal
      elevated area (MEA), 2) the central depressed area (CDA), and 3) the most
      thickened area (MTA). Studies were performed with well known histologic
      parameters to compare the predictive power of tumor thickness on MLM, LNM, and OS
      using the Cox proportional hazards regression model or analysis of variance.
      RESULTS: A significant correlation between tumor thickness and MLM was observed
      only in the CDA in the NCCH patients (P = 0.005). The authors applied a tumor
      thickness cutoff value in the CDA of 10 mm (</= 10 mm and > 10 mm) for further
      study. Multivariate analyses demonstrated that a tumor CDA thickness > 10 mm was
      associated significantly with MLM, multiple LNMs, and OS in NCCH patients with
      Dukes Stage C disease (P = 0.002, P = 0.023, and P = 0.002, respectively). A
      significant predictive power for tumor CDA thickness for MLM, multiple LNMs, and
      OS was confirmed by multivariate analysis in NCCHE patients with Dukes Stage C
      disease (P = 0.008, P = 0.021, and P = 0.010, respectively). CONCLUSIONS: The CDA
      thickness of the tumor was found to be a useful predictive parameter for MLM,
      multiple LNMs, and OS in patients with Dukes Stage C ulcerative-type colorectal
      carcinoma who were being treated in two independent hospitals.

PMID- 10896997
TI  - Concomitant chemoradiation treatment in the management of patients with
      extrahepatic biliary tract recurrence of gastric carcinoma.
AB  - BACKGROUND: The aim of this study was to determine the role of concomitant
      chemoradiation in the alleviation of obstructive jaundice in patients with
      extrahepatic biliary tract metastases from gastric carcinoma. METHODS: Thirteen
      patients with good performance status who had obstructive jaundice resulting from
      extrahepatic biliary metastases after gastrectomy for gastric carcinoma were
      treated with palliative intent. Treatment consisted of insertion of a
      percutaneous transhepatic choledochal drainage (PTCD) catheter followed by
      external radiation up to a total dose of 40-60 grays in combination with
      chemotherapy (cisplatin 20 mg/m(2)/day, 5-fluorouracil 600 mg/m(2)/day, and
      leucovorin 90 mg/m(2)/day for 96 hours during the first and fifth weeks) on an
      outpatient basis. RESULTS: The concomitant chemoradiation produced a good
      palliative effect in all 13 patients. Hyperbilirubinemia continued to improve
      after treatment, patients' clay-colored stool resolved within an average of 4
      weeks (range, 2-6 weeks), and bilirubin levels returned to normal. The PTCD
      catheter could be removed after treatment was completed (the seventh week); the
      mean duration of PTCD placement was 2 months. The entire treatment course was
      performed on an outpatient basis; hospital admission was necessary only for PTCD
      insertion and chemotherapy. Ten patients died of their disease, with an average
      survival of 14.4 months (range, 4-31 months) from the time of PTCD insertion.
      Three patients are still alive at 16, 21, and 8 months. Biliary tract patency was
      maintained until death. No serious treatment-related complications occurred, and
      no endoprothesis or intraluminal brachytherapy was needed in this study.
      CONCLUSIONS: Satisfactory palliation can be achieved by concomitant
      chemoradiation for patients with obstructive jaundice resulting from extrahepatic
      biliary metastases from gastric carcinoma, providing an alternative treatment
      choice for these patients.

PMID- 10896999
TI  - Comparative screening with a sensitive guaiac and specific immunochemical occult
      blood test in an endoscopic study.
AB  - BACKGROUND: HemoccultSENSA (HOS), the sensitive guaiac fecal occult blood test
      (FOBT) for colorectal neoplasia, is faulted for its low specificity, which might
      be improved by substituting or adding FlexSure OBT (FS), the immunochemical test
      for human hemoglobin. (Both tests are manufactured by Beckman-Coulter Inc.,
      Primary Care Diagnostics, Palo Alto, CA.) The authors compared both FOBTs in an
      endoscopic study to determine which FOBT to recommend for a population-screening
      program. METHODS: Both FOBTs, without dietary restrictions, were prepared by 1410
      screenees or nonbleeding symptomatic patients (3%). All underwent colonoscopy
      (51.8%) or flexible sigmoidoscopy (if asymptomatic and both FOBTs were negative).
      RESULTS: HOS sensitivity for significant neoplasia, cancers, or adenomas >/= 1 cm
      (20 cases) was similar to that of FS (50% vs. 35%, not significant). However, HOS
      specificity was lower (95% vs. 99%, confidence interval (CIs) 94-96 vs. 98-99, P
      < 0.05). In those 11 cases in which both HOS and FS were positive, specificity
      for significant neoplasia was 100% but sensitivity decreased to 25% (less than
      HOS alone, P < 0.05). HOS was more sensitive than FS for any neoplasia (55
      cases), including adenomas < 1 cm (35% vs. 18%, CIs 22-47 vs. 8-28, P < 0.05),
      but less specific (96% vs. 99%, CIs 95-97 vs. 98-100, P < 0.05). CONCLUSIONS:
      Guaiac HOS, which does not require dietary restrictions, is significantly more
      sensitive for any colorectal neoplasm than the immunochemical FS; it identifies
      more adenomas with a specificity that is low but acceptable for population
      screening.

PMID- 10897000
TI  - Analysis of factors affecting the appearance of hepatocellular carcinoma in
      patients with chronic hepatitis C. A long term follow-up study after histologic
      diagnosis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) occurs more frequently in patients
      with hepatitis C virus (HCV)-related chronic liver disease than those with
      hepatitis B virus-related disease. It is important to assess the factors
      affecting the development of HCC. METHODS: A long term follow-up study involving
      patients with chronic HCV was performed retrospectively. A total of 153 patients
      diagnosed between June 1981 and November 1990 with chronic HCV with or without
      cirrhosis by liver biopsy were enrolled in a long term follow-up study (average,
      99.4 months) and the cumulative incidence rate of HCC and factors affecting the
      appearance of HCC were examined. RESULTS: The 5-year cumulative incidence rate
      was 9%, the 10-year cumulative incidence rate was 23%, and the 15-year cumulative
      incidence rate was 42%. The annual rate of incidence increased as the follow-up
      period progressed. The authors selected ten variables and investigated their
      effect on the incidence rate of HCC, including age, gender, habitual heavy
      drinking, positivity of antibody against hepatitis B virus surface antigen,
      treatment with interferon (IFN) during the follow-up period, maximum and minimum
      serum alanine aminotransferase levels during the follow-up period, histologic
      staging, grading, and irregular regeneration of hepatocytes. Of the 10 variables,
      age (> 50 years), habitual heavy drinking, and histologic staging were determined
      to be independent risk factors according to multivariate Cox proportional hazards
      regression analysis. IFN therapy by itself was not found to be an independent
      factor affecting the appearance of HCC. CONCLUSIONS: In patients with chronic
      HCV, the annual incidence rate of HCC appeared to increase as the follow-up
      period progressed. According to the results of the current study, the factors
      that independently affected the development of HCC were age, habitual heavy
      drinking, and histologic staging.

PMID- 10897001
TI  - p16 is a major inactivation target in hepatocellular carcinoma.
AB  - BACKGROUND: The p16(INK4A) gene encodes 2 cell cycle regulator proteins, p16 and
      p14(ARF), by alternative splicing. This genetic locus also contains another cell
      cycle regulator gene, p15(INK4B), which encodes p15. The inactivation of the p16
      protein has been demonstrated in some hepatocellular carcinomas (HCCs); however,
      the inactivation of the other 2 cell regulator proteins and their inactivation
      patterns are not well characterized. METHODS: To characterize the role of the
      above 3 cell cycle regulator proteins in HCCs, the authors examined the genomic
      status of the p16(INK4A) and p15(INK4B) genes and their RNA products in 20 HCC
      tissues and 7 human HCC cell lines. Homozygous deletions in each exon of
      p16(INK4A) and p15(INK4B) were evaluated by comparative multiplex polymerase
      chain reaction (PCR), and the methylation status of the p16(INK4A) and p15(INK4B)
      promoter region was analyzed by methylation specific PCR. RESULTS: Homozygous
      deletions were found in 6 of 20 HCCs (30%) and 2 of 7 HCC cell lines (29%). In 20
      HCCs, the frequency of homozygous deletions was 20% in exon 1 of p15(INK4B), 20%
      in exon 2 of p15(INK4B), 10% in exon 1beta of p16(INK4A), 25% in exon 1alpha of
      p16(INK4A), 15% in exon 2 of p16(INK4A), and 15% in exon 3 of p16(INK4A). The
      authors found hypermethylation of the p16(INK4A) promoter region in 7 HCCs (35%)
      and 3 HCC cell lines (43%). The overall frequency of p16 alterations in HCCs,
      including hypermethylation and homozygous deletions, was 60% (12 of 20 cases).
      According to reverse transcriptase-PCR analysis, the absence of RNA expression
      was most frequent in p16 (11 of 20 cases, 55%) and less frequent in p15 (7 of 20
      cases, 35%) and p14(ARF) (5 of 20 cases, 25%). CONCLUSIONS: Among the 3 cell
      cycle regulator proteins encoded at the 9p21 genetic locus, inactivation of p16
      is the most frequent event in HCCs in which promoter hypermethylation and
      homozygous deletions are the common mechanisms.

PMID- 10897002
TI  - Six-year recurrence free survival after intraluminal iridium-192 therapy of human
      bilobar biliary papillomatosis. A case report.
AB  - BACKGROUND: Biliary papillomatosis is rare and often fatal. Liver resection or
      transplantation is recommended but may be impossible due to tumor or patient
      factors; furthermore, it appears to the authors of this study that no follow-up
      results after transplantation have been reported in previous studies. METHODS:
      Bilobar but limited biliary papillomatosis in a man age 54 years was mapped by
      cholangiopancreatography, cholecystectomy, and operative cholangioscopy. After
      cholangioscopic electrocoagulation, iridium-192 wires were temporarily inserted
      into the affected bile ducts, giving a dose of 60 grays at a 3-mm distance.
      Another percutaneous cholangioscopic electrocoagulation was performed 3 weeks
      later. RESULTS: The patient has been free of tumor and in good health for 80
      months, but he has a long term stenting of a nonneoplastic stricture at the
      confluence of the bile ducts. CONCLUSIONS: Mechanical tumor reduction and
      intraluminal brachytherapy could possibly replace transplantation (which up to
      now has been suggested but not reported) when this life-threatening disease is
      bilobar, and also possibly replace liver resection for limited tumors in patients
      who are too frail for surgery.

PMID- 10897003
TI  - Epidermal growth factor receptor blockade by antibody IMC-C225 inhibits growth of
      a human pancreatic carcinoma xenograft in nude mice.
AB  - BACKGROUND: Pancreatic carcinoma is associated with a poor prognosis, and
      treatment options for patients with this disease are limited. The epidermal
      growth factor (EGF) receptor and its ligands are overexpressed in human
      pancreatic carcinoma and may contribute to the pathophysiology of these tumors.
      METHODS: The anti-EGF receptor monoclonal antibody IMC-C225 was used to determine
      the effects of EGF receptor blockade on the growth of human pancreatic carcinoma
      BxPC-3 cells in vitro. Athymic mice bearing established (200 mm(3)) subcutaneous
      BxPC-3 xenografts were treated with IMC-C225 (17 or 33 mg/kg every 3 days) alone
      or in combination with 5-fluorouracil (17 mg/kg twice weekly). RESULTS: IMC-C225
      inhibited exogenous ligand-stimulated tyrosine phosphorylation of the EGF
      receptor on BxPC-3 tumor cells. Treatment of BxPC-3 cells with IMC-C225 inhibited
      DNA synthesis (23.8%) and colony formation in soft agar (45.6%). IMC-C225
      treatment significantly suppressed the growth of BxPC-3 tumors compared with
      treatment with vehicle alone (P = 0.003). Combination therapy with IMC-C225 and
      the chemotherapeutic agent 5-fluorouracil enhanced the antitumor effects compared
      with either agent alone and resulted in regression of pancreatic tumors in
      several animals. Histologic examination of pancreatic tumors from mice treated
      with IMC-C225 showed extensive tumor necrosis that coincided with a substantial
      decrease in tumor cell proliferation and an increase in tumor cell apoptosis.
      CONCLUSIONS: These data suggest that IMC-C225 affects the growth of pancreatic
      tumors by inhibiting EGF receptor-dependent proliferation and survival, and
      demonstrates the potential for therapeutic application of IMC-C225 antibody in
      the treatment of human pancreatic carcinoma.

PMID- 10897004
TI  - Tissue polypeptide specific antigen (TPS), a marker for differentiation between
      pancreatic carcinoma and chronic pancreatitis. A comparative study with CA 19-9.
AB  - BACKGROUND: The value of serum tissue polypeptide specific antigen (TPS) as a
      complement to CA 19-9 in the detection of pancreatic carcinoma was determined
      prospectively. TPS and CA 19-9 levels obtained at the time of diagnosis in
      patients suspected of having chronic pancreatitis or pancreatic carcinoma were
      evaluated in receiver operating characteristic (ROC) curve analysis. METHODS:
      Serum TPS and CA 19-9 levels were measured by immunoassays in 122 subjects, 48
      with pancreatic carcinoma and 74 with chronic pancreatitis. RESULTS: Elevated
      levels of CA 19-9 were detected preoperatively in 70% of pancreatic carcinoma
      patients and in 19% of chronic pancreatitis patients. Elevated levels of TPS were
      detected in 100% of patients with pancreatic carcinoma and in 22% of patients
      with chronic pancreatitis. The median levels of TPS and CA 19-9 for pancreatic
      carcinoma were significantly higher than those for chronic pancreatitis (P <
      0.0001). Increasing the upper reference value of TPS allowed for better
      discrimination between chronic pancreatitis and pancreatic carcinoma. ROC curve
      analysis showed that the introduction of 200 U/L as a decision criterion for TPS
      did not reduce its sensitivity but significantly improved its specificity. At a
      specificity of 98% for TPS, discrimination between pancreatic carcinoma and
      chronic pancreatitis was found to be 97%. Increasing the upper reference level
      for CA 19-9 to attain a specificity of 98% decreased its sensitivity from 70% to
      33%. CONCLUSIONS: At an elevated cut-off level for TPS (200 U/L), almost complete
      discrimination between pancreatic carcinoma and chronic pancreatitis was
      obtained. TPS will be more useful than CA 19-9 in the differential diagnosis of
      pancreatic carcinoma and chronic pancreatitis.

PMID- 10897005
TI  - Phase II study of paclitaxel and epirubicin as first-line treatment in patients
      with metastatic nonsmall cell lung carcinoma.
AB  - BACKGROUND: The combination of paclitaxel and epirubicin has shown a favorable
      interaction in patients with advanced breast carcinoma. Therefore the efficacy
      and toxicity of this regimen was evaluated in a Phase II study of patients with
      metastatic nonsmall cell lung carcinoma (NSCLC). METHODS: Thirty-two chemotherapy
      naive patients with AJCC Stage IV NSCLC and an Eastern Cooperative Oncology Group
      performance status of 0-1 were entered into the study. Patients received
      epirubicin, 90 mg/m(2), followed by paclitaxel, 175 mg/m(2) by 3-hour infusion,
      on Day 1. The treatment was repeated every 3 weeks. Granulocyte-colony
      stimulating factor (G-CSF) was not used routinely. RESULTS: A total of 116
      treatment cycles was delivered. All patients could be assessed for response,
      toxicity, and survival. There were 16 partial responses and no complete
      responses, giving rise to an overall response rate of 50% (95% confidence
      interval, 31. 9-68.1%). The median time to progression in responders was 7
      months. The median survival was 8 months, and the 1-year survival rate was 37%.
      World Health Organization Grade 4 neutropenia occurred in 69% of patients, but
      could be managed easily with G-CSF, which was used in 35% of cycles. Cumulative
      peripheral neuropathy was the main nonhematologic toxicity and was observed in 7
      of 8 patients who received 6 treatment courses (Grade 2-3 in 3 cases) and in 6 of
      11 patients who received 4 cycles (Grade 2 in 2 patients). One patient died
      shortly after the first course of chemotherapy from a ventricular arrhythmia.
      CONCLUSIONS: The combination of paclitaxel and epirubicin was found to be
      effective and well tolerated in chemotherapy-naive patients with metastatic NSCLC
      and warrants further evaluation in a multicenter trial of a larger number of
      patients. Careful cardiac evaluation before treatment is indicated.

PMID- 10897006
TI  - c-MYC and nodular malignant melanoma. A case report.
AB  - BACKGROUND: The incidence of skin cancer has been rising since the 1950s. About
      75% of skin cancer-associated deaths are caused by malignant melanoma. Nodular
      malignant melanoma accounts for 20% of melanocytic malignant tumors and is
      associated with a relatively poor prognosis. Extensive research has been
      undertaken, but a molecular marker that can predict a more aggressive course of
      melanoma still has not been found. METHODS: The authors applied cytogenetic and
      molecular genetic techniques to a case of nodular malignant melanoma. They used
      comparative genomic hybridization (CGH) to identify chromosomal regions affected
      by genomic changes and interphase fluorescence in situ hybridization (FISH) on
      touch preparations of the tissue to elucidate the CGH findings further. To
      investigate the functionality of the affected c-MYC gene, the authors detected
      its transcript via reverse transcription and polymerase chain reaction. RESULTS:
      CGH revealed a copy number gain in the 6p and 8q24-8qter region. FISH with c-MYC
      and centromere eight specific probes revealed that the tumor, in contrast to
      unaffected skin, was characterized by a gain in copy numbers of the c-MYC gene.
      The c-MYC gene transcript was detected at higher levels in the tumor than in the
      tissue taken from the safety margin. CONCLUSIONS: The WAF1 gene located on
      chromosome 6p, which in this case had a copy number gain, might be involved in
      melanoma pathogenesis. The authors suggest that the c-MYC gene plays an important
      role in melanoma development and progression. The c-MYC gene seems to be affected
      by gaining functional copies, leading to a change in the normally regulated gene
      dose effect.

PMID- 10897007
TI  - Carcinoembryonic antigen immunoscintigraphy complements mammography in the
      diagnosis of breast carcinoma.
AB  - BACKGROUND: An adjunctive noninvasive test that is predictable and highly
      specific for breast carcinoma would complement the high false-positive rate of
      mammography in certain patients. METHODS: This prospective, multicenter study
      evaluated the accuracy, safety, and immunogenicity of carcinoembryonic antigen
      (CEA) antibody imaging in women with known or suspected breast carcinoma.
      Scintigraphic breast images were obtained approximately 3-8 hours after the
      administration of technetium 99m ((99)Tc) labeled anti-CEA Fab' and correlated
      with histopathology. RESULTS: The (99)Tc labeled anti-CEA Fab' detected tumor CEA
      expression in 46 of 49 women (94%) initially entered with known primary breast
      carcinoma regardless of histology or serum CEA levels. In women scheduled for
      biopsy confirmation of mammographic and physical examination findings, 104 (99)Tc
      labeled anti-CEA Fab' studies had a sensitivity of 61% (17 of 28 cases) and a
      specificity of 91% (69 of 76 cases). In total, (99)Tc labeled anti-CEA Fab'
      detected 52 of 62 invasive ductal carcinomas, 5 of 5 invasive lobular carcinomas,
      and 3 of 6 noninvasive tumors (2 ductal carcinomas in situ and 1 intracystic
      papillary carcinoma). Tumor size significantly affected sensitivity (P = 0.041),
      with 11 of 14 missed lesions </= T1, and proliferative histology significantly
      affected specificity (P = 0.012), with 5 of 7 false-positive tumors being
      premalignant. In 50 breast carcinoma patients, (99)Tc labeled anti-CEA Fab' also
      demonstrated axillary lymph node involvement regardless of serum CEA levels, with
      a sensitivity of 80% when more than three lymph nodes were positive. No immune
      response or other meaningful side effects occurred. CONCLUSIONS: (99)Tc labeled
      anti-CEA Fab' had high specificity and positive predictive values for breast
      carcinoma and the majority of false-positive studies were associated with an
      increased risk of malignancy. Improved imaging techniques, including dedicated
      gamma cameras for breast and axillary lymph node imaging, will likely improve the
      test's sensitivity for smaller lesions.

PMID- 10897008
TI  - Patterns of recurrence in patients with squamous cell carcinoma of the vulva. A
      multicenter CTF Study.
AB  - BACKGROUND: Invasive vulvar carcinoma is a rare disease with an incidence rate of
      3-5% of all female genital neoplasms. The current study discusses the limited
      number of articles in the literature regarding the patterns of recurrence as well
      as the clinical outcome of patients with recurrent disease based on a consistent
      and consecutive series of cases. METHODS: A common clinical chart focusing on the
      study of patterns of recurrence was used in five Italian gynecologic institutions
      with uniform criteria of surgical nomenclature, pathologic variables, and sites
      of recurrence. Between 1980-1994, 502 cases of primary invasive squamous
      carcinoma of the vulva were registered consecutively, treated, and considered for
      this multicentered study. RESULTS: Of 502 patients, 187 (37.3%) developed a
      recurrence. Distribution of the recurrences by site was as follows: perineal,
      53.4%; inguinal, 18.7%; pelvic, 5.7%; distant, 7.9%; and multiple, 14.2%. In a
      multivariate analysis, 3 characteristics appeared to be statistically correlated
      with the risk of recurrence: International Federation of Gynecology and
      Obstetrics Stage > II (P = 0.029), positive lymph nodes (P = 0.009), and vascular
      space invasion (P = 0.004). The 5-year survival rate was 60% for perineal
      recurrences, 27% for inguinal and pelvic recurrences, 15% for distant
      recurrences, and 14% for multiple recurrences. CONCLUSIONS: In the current study
      the prognostic factors found to have statistical significance as prognostic
      factors for risk of recurrence were tumor dimension, lymph node involvement, and
      stromal and vascular space invasion. The presence of inguinal lymph node
      metastases was predictive of multiple and distant recurrences with a low rate of
      incidence of isolated perineal recurrence (27%) compared with negative lymph node
      cases (57.5%). Survival analysis of recurrent disease showed that the surgical
      resection of local recurrences may provide acceptable results (51% at 5 years).
      This observation may justify a follow-up program aimed at identifying those
      patients with early local recurrence suitable for radical resection.

PMID- 10897009
TI  - Antioxidant enzyme expression and reactive oxygen species damage in prostatic
      intraepithelial neoplasia and cancer.
AB  - BACKGROUND: Oxidative stress results in damage to cellular structures and has
      been linked to many diseases, including cancer. The authors sought to determine
      whether the expression of three major antioxidant enzymes, copper-zinc superoxide
      dismutase (SOD1), manganese superoxide dismutase (SOD2), and catalase, was
      altered in human prostate carcinoma and its likely precursor, high grade
      prostatic intraepithelial neoplasia (PIN). The level of reactive oxygen species
      damage was evaluated by measuring the expression of the DNA adduct 8
      hydroxydeoxyguanosine. METHODS: The authors evaluated the tissue expression of
      the antioxidant enzymes in prostate carcinoma by immunohistochemistry, immunogold
      electron microscopy, and enzymatic assay. The polymerase chain reaction was used
      to amplify and screen tissue specimens for the genes of SOD1, SOD2, and
      extracellular SOD (SOD3). Matched paraffin embedded tissue sections were
      evaluated by RNA in situ hybridization for expression of SOD1 and
      immunohistochemically for the DNA adduct 8-hydroxydeoxyguanosine. RESULTS: All
      prostatic tissues, including cancer, displayed immunoreactivity for the three
      antioxidant enzymes in epithelial cells, with no staining of the stroma,
      inflammatory cells, or endothelial cells. The number of immunoreactive cells was
      greater in benign epithelium than in PIN and cancer for each enzyme. The mean
      percentage and intensity of immunoreactive cells was greatest for SOD2,
      intermediate for SOD1, and lower for catalase. Staining in cancer was
      heterogeneous. Immunogold ultrasound studies revealed strong mitochondrial
      labeling for SOD2, which was greater in benign epithelium than in cancer; SOD1
      labeling was invariably weaker, with nuclear labeling in benign epithelium and
      cytoplasmic labeling in cancer cells. There was no difference in enzyme activity
      for the three antioxidant enzymes between benign epithelium and cancer. No
      mutations were found in the 5 exons of SOD1, 5 exons of SOD2, and 3 exons of
      SOD3, except for 3 of 20 cases with polymorphisms for exon 3 of SOD1. Intense
      nuclear immunoreactivity for 8-hydroxydeoxyguanosine was present in fewer than 3%
      of epithelial cells, with no apparent differences among benign epithelium, PIN,
      and cancer. CONCLUSIONS: SOD1, SOD2, and catalase had lower expression in PIN and
      prostate carcinoma than in benign epithelium. The number of immunoreactive cells
      in PIN was similar to cancer, indicating that these are closely related. Enzyme
      activities were variable, with no difference between benign epithelial cells and
      cancer, although this lack of change in enzyme activity could have been due to
      the presence of contaminating benign cells within the cancer specimens. The
      results of reactive oxygen species damage were found only in the epithelium and
      not in the stroma. Expression of the DNA adduct 8-hydroxydeoxyguanosine was
      present in fewer than 3% of cells, with no apparent differences among benign
      epithelium, PIN, and cancer. These findings suggest that oxidative stress is an
      early event in carcinogenesis.

PMID- 10897010
TI  - Modern prostate brachytherapy. Prostate specific antigen results in 219 patients
      with up to 12 years of observed follow-up.
AB  - BACKGROUND: The purported lack of long term modern prostate brachytherapy outcome
      data continues to lead many physicians to recommend other, more traditional
      treatments. This concern for long term results has encouraged the authors to
      supplement their earlier 10-year follow-up of patients receiving brachytherapy;
      in the process, an additional 77 patients (> 50%) were added to the original
      cohort, and the follow-up time was increased by 2 years. METHODS: Between January
      1987 and September 1989, 229 patients with T1-T3 prostate carcinoma underwent
      transperineal prostate brachytherapy using iodine-125 (I-125). No patient
      received adjuvant hormone therapy. The median Gleason sum was 5 (range, 2-10). Of
      these patients, 147 were determined to have a high probability of organ-confined
      disease and were treated solely with an I-125 implant. The remaining 82 patients
      were determined to be at increased risk for extracapsular disease and received
      pelvic external beam radiation in addition to brachytherapy. All patients were
      followed continuously. Failure was defined as a positive biopsy, radiographic
      evidence of metastases, or three consecutive rises in prostate specific antigen
      (PSA) levels as defined by the American Society for Therapeutic Radiology and
      Oncology (ASTRO) consensus article. RESULTS: Excluding deaths from intercurrent
      disease, the median follow-up was 122 months (range, 18-144 months). Fourteen
      patients were excluded from analysis due to insufficient follow-up. Adopting the
      ASTRO definition of failure resulted in minimal change in survival when compared
      with the authors' previous study, which used a PSA level > 0.5 ng/mL as the
      failure point. Observed 10-year disease free survival (DFS) for the entire cohort
      was 70%. In the brachytherapy only group, the observed 10-year DFS was 66%,
      whereas those patients treated with the addition of external pelvic radiation
      achieved a DFS of 79%. None of the patients who were followed for the full 12
      years failed between Years 10 and 12. Only 25% of the failures observed occurred
      > 5 years after treatment, thus confirming the durability of brachytherapy.
      CONCLUSIONS: Prostate brachytherapy provides excellent long term disease control
      with few late failures reported in the authors' program. The addition of external
      beam radiation appears to confer survival advantages in selected patients. Using
      the ASTRO failure criteria for long term follow-up resulted in no significant
      difference compared with using a PSA failure point of 0.5 ng/mL.

PMID- 10897011
TI  - The management and outcome of bladder carcinoma in Ontario, 1982-1994.
AB  - BACKGROUND: To the authors' knowledge no previous study has described the
      management and outcome of bladder carcinoma on a population-based level. The
      objective of the current study was to describe the characteristics, treatment,
      and outcome of newly diagnosed invasive bladder carcinoma (n = 20,822) reported
      in Ontario, Canada between 1982-1994. METHODS: Electronic records of invasive
      bladder carcinoma (International Classification of Diseases code 188) from the
      Ontario Cancer Registry were linked to surgical and radiotherapy (RT) records.
      Bivariate and multivariate techniques were used to assess variations in the use
      of initial cystectomy and pelvic RT. The authors modeled the likelihood of death
      after diagnosis and the probability of cystectomy free survival. All analyses
      were controlled for age, gender, histology, and year of diagnosis. RESULTS: The
      most common histologic type was papillary transitional cell carcinoma. Maximum
      initial treatment was comprised of total cystectomy (5.1%), partial cystectomy or
      open excision (3. 5%), pelvic RT (5.9%), transurethral resection of the bladder
      (66. 7%), or lesser or no procedures (18.7%). The use of total cystectomy and
      pelvic RT varied among the regions of Ontario. Overall 5-year survival was 58.8%,
      and was 86.5% for patients with papillary histology. In multivariate analysis,
      although survival was similar among the regions, the relative risk of cystectomy
      conditional on survival varied. CONCLUSIONS: Papillary tumors portend a better
      survival than nonpapillary tumors. Variations in the use of total cystectomy and
      in the use of pelvic RT among the regions of Ontario did not appear to be
      associated with variations in survival. However, cystectomy free survival
      appeared to vary among the regions. These results suggest that patients can be
      managed safely using a bladder-preserving approach.

PMID- 10897012
TI  - Increased glyceraldehyde-3-phosphate dehydrogenase expression in renal cell
      carcinoma identified by RNA-based, arbitrarily primed polymerase chain reaction.
AB  - BACKGROUND: Renal cell carcinoma (RCC) comprises 85% of renal tumors and displays
      a great capacity to metastasize. The lack of diagnostic and prognostic markers
      complicates its early detection and in the majority of cases metastases are
      present at the time of diagnosis. METHODS: The current study reports on the
      identification of differentially expressed genes in RCC using random arbitrarily
      primed polymerase chain reaction (RAP-PCR). RESULTS: Four genes were identified,
      including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase
      A (LDH A), human leukocyte antigen A (HLA A), and ferritin. GAPDH and HLA A were
      found to be overexpressed in 100% of the tumors and LDH A was increased in > 85%
      of the tumors analyzed compared with normal kidney counterparts. For GAPDH and
      LDH A higher protein levels in the tumors also were determined by Western blot
      analysis. Differential expression did not appear to correlate with gene
      amplification events as demonstrated by Southern blot analysis, indicating that
      regulatory mechanisms controlling the expression of these genes were altered.
      Finally, ferritin was judged to have a variable expression because it was
      decreased in approximately 50% of the tumors and augmented in 20%. The
      implications in proliferation and differentiation of all these genes were
      analyzed in RCC cell lines grown at different stages of confluency and additional
      information was obtained regarding expression of the GAPDH gene in proliferating
      primary cultures of normal and tumor cells derived from the same kidney samples.
      CONCLUSIONS: The authors conclude that RAP-PCR is a useful technique with which
      to identify rapidly differentially expressed genes in a given system. In
      addition, they also conclude that GAPDH is a potent marker of cell proliferation
      in kidney tumor cells whose overexpression appears to be a late event in the
      development of RCC.

PMID- 10897013
TI  - Cancer risk and mortality in users of calcium channel blockers. A cohort study.
AB  - BACKGROUND: Data regarding the association between the use of calcium channel
      blockers and cancer risk have been conflicting. In the current study, the authors
      examined the cancer risk and mortality in users of calcium channel blockers in
      North Jutland County, Denmark. METHODS: The authors conducted a cohort study
      using record linkage between a population-based prescription database, the Danish
      Cancer Registry, and the Danish Death Registry including 23, 167 users of calcium
      channel blockers who received >/=2 prescriptions between January 1, 1989 and
      December 31, 1995. The authors calculated the standardized incidence ratios and
      standard mortality ratios for cancer, along with corresponding 95% confidence
      intervals (95% CI). RESULTS: Overall, 967 incident cases of cancer occurred,
      resulting in a standardized incidence ratio of 1.04 (95% CI, 0.98-1.11). There
      was a slightly elevated nonsignificant risk of tobacco-related cancer. No
      increased risk of breast or colon carcinoma was observed. The cancer mortality
      was close to that expected in the background population (standardized mortality
      ratio of 0.97; 95% CI, 0.89-1.04). CONCLUSIONS: This large-scale, population
      based cohort study adds to the increasing evidence indicating no substantial
      association between the use of calcium channel blockers and the incidence rate of
      cancer or cancer mortality.

PMID- 10897014
TI  - The accumulation of ascorbic acid by squamous cell carcinomas of the lung and
      larynx is associated with global methylation of DNA.
AB  - BACKGROUND: Cigarette smokers are known to have lower concentrations of
      circulating ascorbic acid than nonsmokers. In contrast, there is evidence that
      the extracellular fluid lining of the alveolus, which comes in close contact with
      cigarette smoke, and the alveolar macrophages of smokers are enriched with
      ascorbic acid. The clinical significance of these observations is unknown.
      METHODS: The authors measured the ascorbic acid concentrations and radiolabeled
      methyl incorporation (which is inversely related to the degree of DNA methylation
      in vivo) of paired samples of squamous cell carcinoma (SCC) and adjacent
      uninvolved mucosa of the lung and larynx (n = 22). RESULTS: Cancerous tissues had
      significantly higher ascorbic acid concentrations (mean +/- standard deviation
      [SD, 485 +/- 77; median, 483 ng/mg protein) compared with their matched
      uninvolved tissues (mean +/- SD, 151 +/- 52; median, 72 ng/mg protein; P <
      0.0001). The radiolabeled methyl incorporation was significantly higher in
      cancerous tissues (mean +/- SD, 31,419 +/- 2629; median, 31,416 counts per minute
      [CPM]/microg DNA) compared with their matched uninvolved tissues (mean +/- SD,
      11,883 +/- 1567; median, 11,444 CPM/microg DNA; P < 0.0001). The Spearman
      correlation between ascorbic acid concentrations and radiolabeled methyl
      incorporation by DNA in SCCs was inverse and statistically significant (r = 
      0.58, P = 0.008), indicating a beneficial effect of accumulated ascorbic acid in
      global methylation of DNA. In the uninvolved tissues, this correlation was
      inverse but statistically not significant (r = -0.20, P =0.35). CONCLUSIONS:
      Cancerous tissues of the lung and larynx demonstrated their ability to accumulate
      ascorbic acid. The accumulation of ascorbic acid by these tissues seemed to
      facilitate global methylation of DNA.

PMID- 10897015
TI  - The efficacy of a combination of etoposide, ifosfamide, and cisplatin in the
      treatment of patients with soft tissue sarcoma.
AB  - BACKGROUND: Successful chemotherapy for patients with soft tissue sarcoma (STS)
      has been limited by a lack of active drugs. The most effective single agents are
      doxorubicin, dacarbazine, and, more recently, ifosfamide. Previously the most
      widely used combination has been CYVADIC (cyclophosphamide, vincristine,
      doxorubicin, and dacarbazine). In one randomized trial, ifosfamide was superior
      to cyclophosphamide; two nonrandomized studies also reported favorable results.
      Etoposide monotherapy was successful in 8%; the effectiveness of cisplatin was 5
      23%. In view of these findings, the authors treated STS patients with an
      etoposide, cisplatin, and ifosfamide (VIP) combination. METHODS: The eligibility
      criteria included histologically confirmed, inoperable, metastatic or locally
      recurrent STS; a World Health Organization (WHO) performance status of 0-2; a
      maximum age of 75 years; and progressive, measurable disease. A total of 104
      patients were treated from January 1990 to June 1997. The median age of the
      patients was 42.4 years. The patients were treated with a combination of
      etoposide (100mg/m(2) for 5 days), ifosfamide (2000 mg/m(2) for 2 days), and
      cisplatin (20mg/m(2) for 5 days) once a month via a peripheral vein. The
      treatment response and the toxicity were assessed according to WHO criteria.
      RESULTS: Of 104 evaluable patients, 47 responded. The overall response rate was
      46% (complete response: 10%; partial response: 36%). In 43 patients the disease
      remained stable (41%). Remission duration was 4.6 months. Toxicity was moderate.
      The main adverse events were alopecia (100%), nausea and vomiting (73%), and
      leukopenia (29%). CONCLUSIONS: This new combination is promising for the
      treatment of patients with advanced STS.

PMID- 10897016
TI  - Cancer stage at diagnosis, treatment, and survival among American Indians and non
      American Indians in Montana.
AB  - BACKGROUND: The intent of the current study was to ascertain whether differences
      in cancer survival between Montana non-American Indians (non-AI) and Montana
      American Indians (AI) were related to differences in stage of disease at
      diagnosis or in the type of treatment received. METHODS: A case-control design
      was utilized using data from the Montana Central Tumor Registry and the Indian
      Health Service medical records. AIs diagnosed between January 1, 1984 and
      December 31, 1993 were the cases in the study, and non-AIs diagnosed in the same
      period were the controls. Chi-square tests and life table techniques were used to
      analyze the data. RESULTS: Five hundred twenty-two cases were matched with
      controls. The 5-year cancer survival rate for AIs was 36% and was 47% among non
      AIs. The stage at the time of diagnosis was local in 34% of AIS and 36% of non
      AIs. The stage was regional in 30% of AIs and 26% of non-AIs. Distant disease at
      the time of diagnosis was present in 25% of AIs and 24% of non-AIs, whereas an
      unknown extent of disease was present in 11% of AIs and 14% of non-AIs. AIs
      underwent surgery less frequently than non-AIs (79% vs. 86%), but this did not
      appear to contribute to the survival differences observed. CONCLUSIONS: The
      survival differences observed in the current study cannot be explained easily by
      differences in the cancer stage at diagnosis or the type of treatment received.

PMID- 10897017
TI  - The UICC Telepathology Consultation Center. International Union Against Cancer. A
      global approach to improving consultation for pathologists in cancer diagnosis.
AB  - BACKGROUND: The morphologic diagnosis of tumor specimens with precise tumor
      typing, staging, and grading remains the basis of almost all cancer treatments.
      Thus, in each tumor case, a histologic diagnosis of the highest quality should be
      the physician's priority. In approximately 10-20% of tumor cases, diagnostic
      uncertainty remains to some degree, requiring a second opinion in determining the
      biologic behavior, the histogenesis, the grade of dedifferentiation, or any other
      parameter. Facilitating the communication between pathologists and the exchange
      of cases, telepathology gains more and more importance. To benefit from this
      technical development, the International Union Against Cancer (UICC) has decided
      to establish a Telepathology Consultation Center (UICC-TPCC) for interested
      pathologists around the world. METHODS: The communication and exchange of
      histologic images works via the Internet. To ensure constant documentation, a
      case-based data base and image archive is used. Special TPCC software handles all
      requests to the TPCC and controls the interaction among requesting pathologists,
      TPCC, and UICC experts (transferring, reading, answering, logging, storing,
      etc.). All necessary data for controlling the telepathology service are stored in
      a customized SQL data base. The necessary equipment for the requesting
      pathologist is a personal computer; a digital or television camera/frame grabber,
      which is attached to a microscope; and access to the Internet. The requesting
      party contacts the TPCC's World Wide Web server and uploads the images and the
      clinical data of their case. To ensure uninterrupted functioning, the hardware
      will be part of a high-level communication center, which is connected via ATM
      (asynchronous transfer mode, 155 megabits per second) to the Internet. RESULTS:
      The UICC has decided to establish the TPCC at the Institute of Pathology at the
      Charite, Humboldt-University, Berlin, Germany. The TPCC will not make the
      diagnoses itself but will involve an affiliated specialized expert pathologist.
      He or she will be on the panel of UICC experts who will constitute the
      "diagnostic backbone" of the TPCC. The center will function as follows: If a
      pathologist anywhere on the globe is confronted with the diagnosis of a difficult
      tumor case, he takes digitized histologic images (5-40 in number) and sends them
      along with sufficient clinical data to the server of the UICC-TPCC, asking for a
      second opinion. The center checks the case and transfers it to one of the UICC
      experts. This expert makes his or her diagnostic suggestion, which is then
      transferred back to the requesting pathologist via the UICC-TPCC. CONCLUSIONS:
      The UICC-TPCC will be able to provide rapid and inexpensive diagnostic aid to
      pathologists all over the world, offering the possibility of a second opinion in
      accordance with the UICC-TNM and World Health Organization (WHO) standards.
      During the first and second year, the UICC-TPCC will be financed by sponsors.
      Telepathology makes the distribution of new developments of diagnostic standards,
      e.g., of the TNM system, WHO terminology, new tumor classifications, and updated
      information on actual technologies, globally accessible in a direct and rapid
      way. It also enables a high quality of education and teaching.

PMID- 10897018
TI  - Patterns of care for patients with primary differentiated carcinoma of the
      thyroid gland treated in Germany during 1996. U.S. and German Thyroid Cancer
      Group.
AB  - BACKGROUND: To determine current patterns of care and disease characteristics for
      patients with thyroid carcinoma, a Patient Care Evaluation Study was initiated in
      1996 in the U.S. and Germany. This project addresses ongoing concerns with
      respect to the diagnostic evaluation and treatment of patients diagnosed with
      thyroid carcinoma and raises questions concerning how physicians are interpreting
      current standards and acting on the basis of these recommendations. METHODS:
      Patients with primary thyroid carcinoma were entered into a prospective
      multicenter observational study with free choice of treatment (no control group)
      between January 1, 1996 and December 31, 1996 in Germany. This resulted in a
      total of 2537 cases under observation and analysis; 1685 patients had papillary
      carcinoma (66.4%), 691 had follicular carcinoma (27.2%), 70 had medullary
      carcinoma (2.8%), and 91 had anaplastic carcinoma (3.6%). The 2376 patients with
      carcinoma of either papillary or follicular histology were included in the
      current analysis. RESULTS: The major symptoms reported for patients with
      papillary and follicular thyroid carcinoma was neck mass (reported in 76% and
      79%, respectively) followed by dysphagia (reported in 25% and 27%, respectively),
      stridor (reported in 9% and 14%, respectively), and neck pain (reported in 7% and
      8%, respectively). Greater than 50% of the patients with papillary thyroid
      carcinoma were reported to have American Joint Committee on Cancer/International
      Union Against Cancer Stage I disease. Between 37-39% of the follicular carcinoma
      patients had Stage I and Stage II disease. Only slight differences in the
      diagnostic approach to patients with papillary or follicular carcinoma were
      noted. The majority of patients underwent an ultrasound of the thyroid region
      (78.1%), which was suggestive of carcinoma in only 39% of the cases. A thyroid
      scan was performed on 76.6% of patients, and the results were suggestive of
      carcinoma in 44.8% of the individuals. In contrast, fine-needle aspiration biopsy
      of the thyroid is highly recommended in the current Clinical Practice Guidelines
      (CPG) but results were obtained in only 27.4% of the patients. Total
      thyroidectomy without lymph node dissection was the most commonly used surgical
      procedure in the treatment of patients with papillary and follicular thyroid
      carcinoma. Only approximately 2% of patients at low risk in the group with Stage
      I disease were treated with a lobectomy. In 80% of the patients with Stage I
      papillary thyroid carcinoma and approximately 90% of those patients diagnosed
      with Stage II, III, and IV disease treating physicians chose to utilize
      radioiodine as adjuvant treatment after disease-directed surgery. External beam
      radiation was added to the treatment regimen for many patients diagnosed with
      Stage III and IV disease (30% in patients with papillary thyroid carcinoma and
      33% in patients with follicular thyroid carcinoma). CONCLUSIONS: To the authors'
      knowledge no single effective diagnostic test for thyroid carcinoma currently is
      available and in the majority of cases a combination of ultrasound, thyroid scan,
      or fine-needle aspiration biopsy together with the clinical findings (e.g.,
      thyroid mass) led to a diagnosis of carcinoma. The authors suspect that the high
      prevalence of concomitant pathologic findings such as goiter, even in the healthy
      population in Germany, reduces the accuracy of all diagnostic test methods and
      may account for the frequent use of imaging techniques. The majority of patients
      underwent a total or near-total thyroidectomy. Total thyroidectomy with radical
      lymph node dissection was used very frequently in those patients with papillary
      thyroid carcinoma (22%). German physicians tend to surgically treat early stage
      thyroid carcinoma somewhat more radically than recommended in the CPG. With
      respect to other treatment options employed as part of the first course of
      treatment, radioiodine appears to play the most important role. [See commentary o

PMID- 10897019
TI  - Initial results from a prospective cohort study of 5583 cases of thyroid
      carcinoma treated in the united states during 1996. U.S. and German Thyroid
      Cancer Study Group. An American College of Surgeons Commission on Cancer Patient
      Care Evaluation study.
AB  - BACKGROUND: The American College of Surgeons Commission on Cancer (CoC) has
      conducted national Patient Care Evaluation (PCE) studies since 1976. METHODS:
      Over 1500 hospitals with CoC-approved cancer programs were invited to participate
      in this prospective cohort study of U.S. thyroid carcinoma cases treated in 1996.
      Follow-up will be conducted through the National Cancer Data Base. RESULTS: Of
      the 5584 cases of thyroid carcinoma, 81% were papillary, 10% follicular, 3.6%
      Hurthle cell, 0.5% familial medullary, 2.7% sporadic medullary, and 1.7%
      undifferentiated/anaplastic. Demographics and suspected risk factors were
      analyzed. Fine-needle aspiration of the thyroid gland (53%) or a neck lymph node
      (7%), thyroid nuclear scan (39%), and ultrasound (38%) constituted the most
      frequently utilized diagnostic modalities. The vast majority of patients with
      differentiated thyroid carcinoma presented with American Joint Committee on
      Cancer Stage I and II disease and relatively small tumors. For all histologies,
      near-total or total thyroidectomy constituted the dominant surgical treatment. No
      lymph nodes were examined in a substantial proportion of cases. Residual tumor
      after the surgical event could be documented in 11% of cases, hypocalcemia in 10%
      of cases, and recurrent laryngeal nerve injury in 1.3% of cases. Complications
      were most frequently associated with total thyroidectomy combined with lymph node
      dissection. Thirty-day mortality was 0.3%; when undifferentiated/anaplastic
      cancer cases were eliminated, it decreased to 0.2%. Adjuvant treatment, probably
      underreported in this study, consisted of hormonal suppression (50% overall) and
      radioiodine (50% overall). CONCLUSIONS: In addition to offering information
      concerning risk factors and symptoms, the current PCE study compliments the
      survival information from previous NCDB reports and offers a surveillance
      snapshot of current management of thyroid carcinoma in the U.S. Identified
      opportunities for improvement of care include 1) more frequent use of fine-needle
      aspiration cytology in making a diagnosis; 2) more frequent use of laryngoscopy
      in evaluating patients preoperatively, especially those with voice change; and 3)
      improved lymph node resection and analysis to improve staging and, in some
      situations, outcomes.

PMID- 10897020
TI  - A high number of tumor free axillary lymph nodes from patients with lymph node
      negative breast is associated with poor outcome.

PMID- 10897021
TI  - Author reply

PMID- 10897022
TI  - High dose morphine use in the hospice setting. A database survey of patient
      characteristics and effect on life expectancy.

PMID- 10897023
TI  - Author reply

PMID- 10897024
TI  - Derivation of a new hematopoietic cell line with endothelial features from a
      patient with transformed myeloproliferative syndrome. A case report.

PMID- 10897025
TI  - Author reply

PMID- 10897026
TI  - Significance of axillary lymph node extranodal soft tissue extension and
      indications for postmastectomy irradiation.

PMID- 10897027
TI  - Author reply

PMID- 10897028
TI  - Mandatory second opinion surgical pathology at a large referral hospital.

PMID- 10897029
TI  - Author reply

PMID- 10897030
TI  - Author reply

PMID- 10897031
TI  - Acute myelogenous leukemia after exposure to strontium-89 for the treatment of
      adenocarcinoma of the prostate.

PMID- 10897032
TI  - Author reply

PMID- 10897033
TI  - Transformation of BALB3T3 cells caused by over-expression of rat CD98 heavy chain
      (HC) requires its association with light chain: mis-sense mutation in a cysteine
      residue of CD98HC eliminates its transforming activity.
AB  - CD98 is a 125-kDa glycoprotein (GP125) consisting of an 85-kDa heavy chain (HC)
      and a 40-kDa light chain (LC), and is highly expressed on the cell surface of
      activated lymphocytes and various tumor cells. In addition to the regulatory role
      of CD98HC in L-, y(+)L- and Xc-amino-acid transport systems, which are
      principally mediated by CD98LC, we have reported transforming activity of human
      CD98HC. In this study, we established and analyzed BALB3T3 clones transfected
      with cDNAs encoding wild-type and mutated rat CD98HC proteins designated as
      BrH/Wild, C103S, C325S and 103/325, in which 103 and/or 325 cysteine were intact
      or replaced with serine. Flow cytometry with anti-rat CD98HC MAb B3 revealed that
      wild-type and mutated CD98HC transfectants expressed almost the same amounts of
      rat CD98HC proteins on the cell surface. Immunoprecipitation with B3 revealed
      that exogenous rat CD98HC proteins were associated with endogenous mouse CD98LC
      by a disulfide bond in BrH/Wild and C325S, but not in C103S and 103/325
      transfectants. These transfectants showed similar doubling times and leucine and
      arginine transport activities, as compared with BALB3T3 and control transfectants
      in monolayer culture. Wild-type and C325S transfectants, however, formed much
      larger anchorage-independent colonies than C103S, 103/325 and control
      transfectants in soft agar. In addition, wild-type and C325S transfectants showed
      tumorigenicity in nude mice, although C103S, 103/325 and control transfectants
      did not. These findings indicate that over-expression of CD98HC and its disulfide
      linkage with CD98LC at the cell surface result in malignant transformation of
      murine fibroblasts.

PMID- 10897034
TI  - Frequent loss of BRCA1 mRNA and protein expression in sporadic ovarian cancers.
AB  - Germline mutations in the BRCA1 gene cause inherited susceptibility to breast and
      ovarian cancers. However, somatic mutations of BRCA1 are rare in sporadic breast
      and ovarian tumours. To establish whether BRCA1 is altered during the development
      of sporadic ovarian cancer by mechanisms other than somatic mutation, we have
      analysed 57 sporadic epithelial ovarian tumours for BRCA1 protein and RNA
      expression. Reduced or absent protein expression was observed in 90% of tumours.
      Decreased protein expression was significantly associated with a reduction in the
      levels of RNA expression. Somatic mutations of BRCA1 and LOH at the BRCA1 locus
      were detected in 3.5% and 44% of informative tumours, respectively; there was no
      significant correlation between the levels of protein and RNA expression and the
      DNA mutation and/or LOH status. Together, these data suggest that expression of
      BRCA1 is down-regulated at the level of transcription during the development of
      sporadic ovarian cancers.

PMID- 10897035
TI  - The Helicobacter pylori vacA s1, m1 genotype and cagA is associated with gastric
      carcinoma in Germany.
AB  - BACKGROUND: The H. pylori vacuolating cytotoxin encoded by vacA and the cytotoxin
      associated protein encoded by cagA are considered to be important virulence
      determinants that have been implicated in the development of peptic ulcers and
      gastric carcinoma. However, conflicting results regarding the association between
      these virulence factors and clinical disease have been reported from different
      geographic regions. AIMS: To determine the frequency of vacA genotypes,
      vacuolating cytotoxin activity, and cagA in H. pylori isolates obtained from
      patients with gastric cancer in Germany. METHODS: H. pylori isolates were
      obtained from 34 patients with gastric cancer and from 35 subjects with
      asymptomatic H. pylori gastritis. vacA genotypes and cagA were identified by PCR.
      Cytotoxic activity was determined by HeLa cell assays. Gastritis was assessed
      according to the updated Sydney System. RESULTS: The H. pylori vacA s1,m1
      genotype was significantly more frequent in patients with gastric cancer (24/34,
      70.6%) as compared with controls (12/35, 34. 3%) (p = 0.005). Cytotoxic activity
      was detected in 24 (70.6%) and 15 (42.9%) H. pylori isolates from gastric cancer
      patients and controls, respectively (p = 0.03). The cagA gene was identified in
      30 (88.2%) and 21 (60%) H. pylori isolates in the respective groups (p = 0.01).
      CONCLUSIONS: Our study suggests a significant association between the H. pylori
      vacA s1,m1 genotype, cytotoxic activity, cagA, and gastric cancer. Detection of
      H. pylori possessing these virulence determinants may help to identify patients
      being at an increased risk to develop gastric cancer in our population.

PMID- 10897036
TI  - Identification of EWS/FLI-1 transcripts in giant-cell tumor of bone.
AB  - The EWS/FLI-1 fusion gene, resulting from a t(11;22) translocation, plays a key
      role in the pathogenesis of Ewing's sarcoma. We demonstrate the presence of
      EWS/FLI-1 hybrid transcripts also in giant-cell tumor, a bone neoplasm featuring
      intermediate characteristics between benign and malignant lesions. Chimeric
      products were detected by semi-nested PCR after 2 cycles of amplification in
      13/15 cases of giant-cell tumor, and their presence was confirmed by Southern and
      Western blots and fluorescence in situ hybridization. Moreover, 3/8 primary
      cultures of giant-cell tumor showed the same type of hybrid transcript observed
      in the original tumor sample. Sequencing of PCR products confirmed the presence
      of EWS and FLI-1 sequences in these products. Detection of EWS/FLI-1 fusion
      transcripts in giant-cell tumor of bone provides a model for the study of the
      transforming mechanisms of the EWS/FLI-1 fusion gene in mesenchymal tumors.

PMID- 10897037
TI  - The alpha 3 beta 1 integrin is associated with mammary carcinoma cell metastasis,
      invasion, and gelatinase B (MMP-9) activity.
AB  - The alpha 3 beta 1 integrin is elevated in several types of metastatic tumor and
      has been associated with increased migration and invasion. Our analysis of a
      series of mammary carcinomas of different histotypes and their corresponding
      metastases demonstrated significantly increased expression of alpha 3 beta 1 in
      the tumor metastases. We therefore studied alpha 3 beta 1 expression of several
      human breast carcinoma cell lines and its association with the invasive
      phenotype. The MDA-MB-231 cell line expressed high levels of the beta1, alpha 2,
      alpha 3, alpha 5, and alpha 6 integrin subunits along with moderate levels of the
      alpha v beta 3 integrin. This line was highly migratory and the most invasive
      using a chemo-invasion assay. In contrast, the other lines tested, MDA-MB-145,
      MCF-7, and SK-BR-3, showed lower migratory and invasive activity and reduced
      alpha 3 integrin subunit expression. Metalloproteases capable of degrading
      collagen IV are necessary for the invasive process. RT-PCR showed that MDA-MB-231
      cells expressed MMP-9, but not MMP-2, gelatinase/collagenase IV. Gelatin
      zymography demonstrated that invading MDA-MB-231 cells released high levels of
      MMP-9 gelatinase activity. A direct role for this gelatinase in MDA-MB-231 cell
      invasion was confirmed by inhibition of invasion using the metalloprotease
      inhibitor Batimastat. Treatment of MDA-MB-231 cells with a function-blocking anti
      alpha 3 antibody strongly inhibited migration and invasion. This correlated with
      a marked reduction in MMP-9 activity produced by MDA-MB-231 cells, suggesting a
      role for alpha 3 beta 1 ligand binding in cell signaling and regulation of
      extracellular matrix degradation.

PMID- 10897038
TI  - Apoptosis induced by extracellular glutathione is mediated by H(2)O(2) production
      and DNA damage.
AB  - The biochemical basis of the anti-proliferative effect of exogenous glutathione
      was investigated in A2780 ovarian carcinoma cells. Previous observations have
      implicated gamma-glutamyl transpeptidase-mediated pro-oxidant reactions as a
      primary mechanism of the extracellular effects of glutathione. In 2 cell lines
      (A2780 and IGROV-1), glutathione led to H(2)O(2) production, but only A2780
      cells, characterized by low expression of detoxification enzymes, were sensitive
      to the thiol compound. In A2780 cells, glutathione exposure resulted in DNA
      single-strand break formation, as measured by alkaline elution. Glutathione
      induced DNA damage generated significant levels of apoptosis in A2780 cells, but
      not in IGROV-1 cells. The capability of glutathione to induce apoptosis was
      associated with cleavage of poly(ADP-ribose)polymerase and with generation of a
      low-molecular-weight form of the pro-apoptotic protein bax. In A2780 cells,
      glutathione exposure was followed by p21 and Bax induction and p53 up-regulation,
      as expected for genotoxic stress. Consistently, analysis of cell-cycle
      perturbations demonstrated the occurrence of G(2)M accumulation after exposure to
      glutathione, similar to what was observed for H(2)O(2). Taken together, these
      results indicate that the cytotoxic effect of extracellular glutathione, related
      to membrane metabolism, is mediated by production of H(2)O(2) leading to DNA
      damage and a cellular response involving p53. These findings might also provide
      insights into the cellular and molecular determinants of chemosensitivity to DNA
      damaging agents, as oxidative stress is implicated in p53-dependent apoptosis.

PMID- 10897039
TI  - HER-2/neu is expressed in human renal cell carcinoma at heterogeneous levels
      independently of tumor grading and staging and can be recognized by HLA-A2.1
      restricted cytotoxic T lymphocytes.
AB  - The HER-2/neu oncoprotein, a 185 kDa membrane-associated tyrosine kinase with
      extensive homology to the epidermal growth factor receptor (EGF-R), is
      overexpressed in breast and ovarian carcinomas. Its overexpression is closely
      associated with poor prognosis in the course of disease. Here we demonstrate HER
      2/neu overexpression in both established cell lines and biopsy material obtained
      from renal epithelial tumors. Immunohistochemical analysis of human kidney tumor
      lesions using 2 HER-2/neu-specific antibodies revealed HER-2/neu expression in
      more than 40% of primary epithelial renal tumors and more than 30% of primary
      renal cell carcinoma (RCC) specimens. A distinctive HER-2/neu expression pattern
      was found in different subtypes of kidney tumors with the highest frequency in
      chromophilic and chromophobic RCC, but neither associated with disease stage nor
      tumor grade. Eight of 10 RCC cell lines expressed significant levels of HER-2/neu
      mRNA and protein, but at a lower level compared with HER-2/neu overexpressing
      ovarian carcinoma cells. To evaluate the immune response against HER-2/neu
      expressing HLA-A2-positive (HLA-A2(+)) RCC cells, allogeneic HLA-A2-restricted
      cytotoxic T-lymphocyte (CTL) lines generated by pulsing dendritic cells with 3
      different HER-2/neu-derived peptides, (HER-2(9.369), HER-2(9.435) and HER
      2(9.689), were utilized in chromium-release assays. Specific lysis of HER-2/neu
      expressing HLA-A2(+) RCC cell lines was mediated by CTL lines specific for each
      of these 3 HER-2/neu-derived epitopes. The fine specificity of 2 CTL clones was
      defined to the epitopes HER-2(9.435) and HER-2(9.689). Their specificity was then
      confirmed by cold target inhibition assays. In addition, CTL-mediated lysis was
      enhanced by pulsing tumor cells with exogenous HER-2/neu-specific peptides. Our
      data suggest that (i) HER-2/neu is heterogeneously expressed in different
      subtypes of RCC, (ii) HER-2/neu is naturally processed by RCC and (iii) HER-2/neu
      epitopes presented by RCC can be recognized by HLA-A2-restricted, HER-2/neu
      specific CTL.

PMID- 10897040
TI  - Up-regulation of alpha 2 beta 1 integrin cell-surface expression protects A431
      cells from epidermal growth factor-induced apoptosis.
AB  - High epidermal growth factor (EGF) concentration (10(-8) M) induces inhibition of
      A431 cell proliferation, resulting in part from an apoptotic process. For some
      cells escaping this process, proliferation was associated with a decrease in
      apoptosis. Moreover, these surviving cells displayed marked morphological changes
      consisting of filopodia formation and cell aggregation. Disrupting cell-cell
      contacts by lowering extracellular calcium concentration reversed the resistance
      process, suggesting that apoptosis protection by aggregation may involve
      intercellular adhesion and cell-cell survival signals probably mediated by
      calcium-requiring molecules such as integrins. From a panel of integrins tested,
      only alpha 2 beta 1 integrin cell-surface expression was up-regulated after high
      apoptotic EGF treatment, and this up-regulation was not observed under a growth
      stimulatory EGF concentration (10(-11) M). Double-labeling analysis (alpha 2 beta
      1/DNA) implicated alpha 2 beta 1 integrin in the resistance process since 99% of
      cells that up-regulated alpha 2 beta 1 integrin survived a high dose of EGF.
      Moreover, the involvement of alpha 2 beta 1 integrin up-regulation in the
      survival of A431 cells that escape EGF-induced apoptosis was verified using the
      blocking anti-alpha 2 beta 1 integrin antibody, which was shown to decrease the
      survival of EGF-stimulated cells. Furthermore, under our culture conditions,
      alpha 2 beta 1 integrin-dependent cell-cell adhesion can be inhibited without
      affecting other cell-adhesive interactions, suggesting that alpha 2 beta 1
      integrin is involved more directly in cell-cell interaction than in cell
      substrate adhesion. Our results provide evidence that EGF-induced up-regulation
      of alpha 2 beta 1 integrin contributes to the enhancement of cell-cell adhesion,
      leading to cell aggregate formation, which permits the escape of A431 cells to
      EGF-induced death by alpha 2 beta 1 integrin signaling.

PMID- 10897041
TI  - Characterization of the expression pattern of p63 alpha and delta Np63 alpha in
      benign and malignant oral epithelial lesions.
AB  - The p53 homologue p63 is essential for ectodermal differentiation, such that p63
      /- mice lack all squamous epithelia and teeth. The p63 gene expresses at least 6
      different transcripts, but information regarding the expression, regulation and
      function of the different isoforms has remained sparse, due to the lack of
      adequate reagents directed specifically against the individual proteins. Here we
      characterize the expression of p63 alpha/delta Np63 alpha in benign and malignant
      lesions of the oral epithelium, using a specific antibody raised against a
      peptide derived from the C-terminus of p63 alpha, which does not cross-react with
      p53 or the other p53 homologue, p73. By immunohistochemical analysis, we show
      that these p63 isoforms are expressed in the nucleus of many cells. In normal and
      benign lesions, p63 alpha/delta Np63 alpha-expressing cells are mainly found
      suprabasally, whereas p53-expressing cells are restricted to the basal-cell
      layer. By RT-PCR, we show that delta Np63 alpha is the predominant isoform in
      cell lines from squamous-cell carcinomas of the head and neck, confirming our
      immunochemical observations. Our data are consistent with studies suggesting a
      role for p63 in the transit-amplifying population of epidermal cells. Over
      expression of p63 alpha, and in particular the delta N form, was frequently seen
      in carcinomas. Taken together with previous analyses of p63 expression, our data
      suggest distinct roles for different p63 isoforms in the regulation of growth
      and/or differentiation of epithelial cells. Moreover, our data are compatible
      with the notion that p63 can act to promote neoplastic growth in the oral
      epithelium.

PMID- 10897043
TI  - HTLV-I infection among Nivkhi people in Sakhalin: comparative serologic and
      phylogenetic analyses for 9 years.

PMID- 10897042
TI  - IGFBP-3 mediates TGF beta 1 proliferative response in colon cancer cells.
AB  - Many human tumor cells are resistant to growth inhibition by TGF beta 1.
      Resistance may be caused by mutations in TGFbeta receptors or in other components
      of the TGF beta signal transduction systems, or by knockout of the retinoblastoma
      (Rb) gene, which in fibroblasts converts cellular response to TGF beta 1 from
      growth inhibition to growth stimulation. Our earlier studies showed such a switch
      in response to TGF beta 1 occurred in 45% of colon cancers but without deletion
      of Rb. We now show that insulin-like growth factor binding protein 3 (IGFBP-3)
      mediates the TGF beta 1-induced proliferation of 3 metastatic or highly
      aggressive colon carcinoma cell lines. TGF beta 1 increases IGFBP-3 abundance
      while phosphorothiolated antisense oligonucleotides to IGFBP-3 block the growth
      promoting effect of TGF beta 1 in each of 3 lines.IGFBP-3 induces carcinoma cell
      growth in a dose-dependent and time-dependent manner in vitro. IGFBP-3 may confer
      a selective growth advantage on tumor cells in vivo because levels of mature
      IGFBP-3 were elevated at least 2-fold in 7 of 10 resected colon cancers compared
      with adjacent normal tissue.

PMID- 10897044
TI  - Pharmacokinetics and microdistribution of polyethylene glycol-modified humanized
      A33 antibody targeting colon cancer xenografts.
AB  - Therapeutic proteins have been conjugated with polyethylene glycol (PEGylation)
      to reduce immunogenicity and enhance circulating dose. Here we have investigated
      the effect of PEGylation on immunogenicity, pharmacokinetics, and histologic
      microdistribution of tumor-targeting antibodies with humanized A33 antibody
      (huA33) as a model system. Conjugation of huA33 with methoxy-PEG of M(r) 5,000
      (32%-34% of primary amines modified) or M(r) 20,000 (16%-18% modification)
      preserved >50% of native huA33 binding to SW1222 colon cancer cells. In mice,
      both PEGylated forms cleared from serum moderately slower than native huA33.
      After repeated immunization with PEG-huA33, antiantibody titers in
      immunocompetent mice were <5% of those in huA33-treated controls. Both PEG-huA33
      forms reached approx. 75% of the maximum tumor dose of huA33 in SW1222
      xenografted mice, but their tumor:blood ratios were considerably reduced. To
      demonstrate immunologic specificity of PEG-huA33 targeting in SW1222 tumor
      bearing mice, antigenic sites were presaturated by injecting excess native huA33.
      This reduced subsequent uptake of PEG-huA33 by up to 80%, whereas presaturation
      with hu3S193 control antibody had no significant effect. To assess the
      microdistribution of antibody uptake in the same xenograft model, tumor tissue
      resected at different time points after antibody administration was examined for
      human IgG by immunohistochemistry. Both PEG preparations achieved the same peak
      staining intensity and homogeneity as native huA33 with a delay of several hours.
      Given the measured reduction in immunoreactivity in vitro, these results
      demonstrate that the tumor targeting potential of huA33 in vivo is preserved at
      PEGylation levels sufficient to suppress immunogenicity.

PMID- 10897045
TI  - Evaluation of CD8(+) T-cell frequencies by the Elispot assay in healthy
      individuals and in patients with metastatic melanoma immunized with tyrosinase
      peptide.
AB  - The lack of reproducible, quantitative assays for T-cell responses has been a
      limitation in the development of cancer vaccines to elicit T-cell immunity. We
      utilized the Elispot assay, which allows a quantitative and functional assessment
      of T cells directed against specific peptides after only brief in vitro
      incubations. CD8(+) T-cell reactivity was determined with an interferon (IFN)
      gamma Elispot assay detecting T cells at the single cell level that secrete IFN
      gamma. We studied both healthy individuals and patients with melanoma. Healthy
      HLA-A*0201-positive individuals showed a similar mean frequency of CD8(+) cells
      recognizing a tyrosinase peptide, YMDGTMSQV, when compared with melanoma patients
      prior to immunization. The frequencies of CD8(+) cells recognizing the tyrosinase
      peptide remained relatively constant over time in healthy individuals. Nine HLA
      A*0201-positive patients with stage IV metastatic melanoma were immunized
      intradermally with the tyrosinase peptide together with the immune adjuvant QS-21
      in a peptide dose escalation study with 3 patients per dose group. Two patients
      demonstrated a significant increase in the frequency of CD8(+) cells recognizing
      the tyrosinase peptide during the course of immunization, from approx. 1/16,000
      CD8(+) T cells to approx. 1/4,000 in the first patient and from approx. 1/14,000
      to approx. 1/2,000 in the second patient. These results demonstrate that modest
      expansion of peptide-specific CD8(+) T cells can be generated in vivo by
      immunization with peptide plus QS-21 in at least a subset of patients with
      melanoma.

PMID- 10897046
TI  - Identification of a new HLA-A(*)0201-restricted T-cell epitope from the
      tyrosinase-related protein 2 (TRP2) melanoma antigen.
AB  - For the development of peptide-based immunotherapies, the identification of
      additional tumor antigens and T-cell epitopes is required. Because HLA-A(*)0201
      is the most common allele in Caucasians, who represent the majority of patients
      with melanomas, 6 peptides carrying an HLA-A(*)0201 motif were synthesized from
      tyrosinase-related protein-2 (TRP2) melanoma antigen and tested for binding
      affinity to the HLA allele using processing-defective T2 cells. These peptides
      were then pulsed onto autologous dendritic cells and used to stimulate in vitro
      CD8(+)-enriched T cells isolated from peripheral blood of HLA-A(*)02(+) healthy
      donors or melanoma patients for the induction of specific cytotoxic T lymphocytes
      (CTLs). One peptide, TRP2(288-296) (SLDDYNHLV), the best HLA-A(*)0201 binder,
      elicited specific CTLs from 1 of 4 patients and 3 of 4 healthy donors. The
      induced CTLs from the patient and from 1 donor efficiently recognized HLA
      A(*)02(+) TRP2(+) melanomas as well as COS-7 cells expressing HLA-A(*)0201 and
      TRP2 in an HLA class I-restricted manner, as assessed by cytokine production and
      direct cytolysis. The remaining 2 CTL lines derived from 2 donors displayed low T
      cell receptor avidity, which could lyse melanoma cells in the presence of
      exogenous peptide. Since TRP2 is an antigen expressed in most melanomas,
      identification of the TRP2/HLA-A(*)0201 peptide SLDDYNHLV may facilitate the
      design of present peptide-based immunotherapies for the treatment of a large
      fraction of melanoma patients.

PMID- 10897047
TI  - Cell proliferation and outcome following doxorubicin plus CMF regimens in node
      positive breast cancer.
AB  - At the Istituto Nazionale Tumori of Milan, a randomised adjuvant chemotherapy
      trial was carried out from 1982 to 1990 to compare alternating with sequential
      regimens of doxorubicin and CMF in 403 patients with more than 3 positive
      axillary nodes. Tumour proliferative activity was determined in 71% (285 cases)
      of women entering the clinical study. We investigated the relation between
      proliferative rate, determined as the [(3)H]thymidine labelling index (TLI) on
      tumour specimens obtained at diagnostic surgery, and clinical outcome following
      the 2 regimens, in which the same drugs were administered at the same dose
      intensity but with a different schedule. A high TLI was significantly associated
      with 12-year overall relapse (P = 0.009), distant metastasis (P = 0.001), and
      death (P = 0.002), even in the presence of information provided by tumour size,
      lymph node involvement, oestrogen receptors, and treatment regimen. The highest
      relapse-free survival (RFS) probability (45%, 95% CI 34-55%) was observed for
      patients with tumour TLI <5% and subjected to the sequential treatment. The
      lowest RFS probability (11%, 95% CI 0-26%) was observed for patients with tumour
      TLI >9% following the alternating regimen. Intermediate RFS probabilities,
      ranging from 23% to 34%, were observed for the other kinetic subgroups following
      the 2 treatment regimens. The benefit of sequential administration of doxorubicin
      and CMF was evident mainly in patients with tumours at low to intermediate
      proliferation.

PMID- 10897048
TI  - Targeting of meta-iodobenzylguanidine to SK-N-SH human neuroblastoma xenografts:
      tissue distribution, metabolism and therapeutic efficacy.
AB  - The clinical results of [(131)I]meta-iodobenzylguanidine (MIBG)-targeted
      radiotherapy in neuroblastoma patients is highly variable. To assess the
      therapeutic potential of [(131)I]MIBG, we used the SK-N-SH human neuroblastoma,
      xenografted in nude mice. The model was first characterized for basic parameters
      of MIBG handling in the host species. This demonstrated the presence of both
      strain- and nu/nu mutation-related differences in [(131)I]MIBG biodistribution.
      Fecal and urinary clearance rates of [(131)I]MIBG in mice roughly resemble those
      in humans, but mice metabolize MIBG more extensively. In both species, enzymatic
      deiodination in vivo was not an important metabolic route. Therapy with
      increasing [(131)I]MIBG doses (25-92 MBq) given as single i.v. injections
      resulted in proportionally increasing specific growth delay values (tumor
      regrowth delay/doubling time) of 1 to 5. Using gamma-camera scintigraphy for non
      invasive dosimetry, the corresponding calculated absorbed tumor radiation doses
      ranged from 2 to 11 Gy. We also compared the therapeutic effects of a single
      [(131)I]MIBG administration with those resulting from a more protracted exposure
      by fractionating the dose in 2 to 6 injections or with high dose rate external
      beam irradiation. No therapeutic advantage of a fractionated schedule was
      observed, and 5.5 Gy delivered by low dose-rate [(131)I]MIBG endo-irradiation was
      equi-effective with 5.0 Gy X-rays. The SK-N-SH neuroblastoma xenograft model thus
      appears suitable to evaluate possible treatment improvements to reach full
      potential of MIBG radiotherapy.

PMID- 10897049
TI  - Wide-field radiation as adjunct to adjuvant chemotherapy in high-risk cases with
      early breast cancer: do it or not?

PMID- 10897050
TI  - Therapeutic anti-tumor response induced with epitope-pulsed fibroblasts
      genetically engineered for B7.1 expression and IFN-gamma secretion.
AB  - Mouse fibroblasts (H-2(b)) were genetically engineered to express a co
      stimulatory B7.1 and an IFN-gamma (Fb/IFN-gamma/B7.1). The Fb/IFN-gamma/B7.1
      cells were then pulsed with an ovalbumin epitope (amino acids 257-264, SIINFEKL,
      H-2K(b)-restricted) as a model antigen (Fb/IFN-gamma/B7.1/OVA) and tested for the
      induction of OVA-specific cytotoxic T lymphocytes (CTLs) in C57BL/6 mice (H
      2(b)). Genetically engineered fibroblasts lacking either IFN-gamma or B7.1 were
      constructed and used as controls. Immunization with the Fb/IFN-gamma/B7.1/OVA
      cells induced strong cytotoxic activity against OVA-expressing EL4 (EG7) tumor
      cells but not against other H-2(b) tumor cells, such as EL4, C1498, and B16F1.
      The magnitude of the cytotoxic response in mice with the Fb/IFN-gamma/B7.1/OVA
      cells was significantly higher than that in mice immunized with any other cell
      construct. CD8(+) T cells with OVA-specific cytotoxic activity were predominant
      in mice immunized with Fb/IFN-gamma/B7.1/OVA cells. Furthermore, treatment with
      Fb/IFN-gamma/B7.1/OVA cells significantly prolonged the survival period of EG7
      tumor-bearing mice. Anti-tumor CTL immunity by the Fb/IFN-gamma/B7.1/OVA cells
      could be induced without the help of host antigen-presenting cells, CD4(+) T
      cells, or NK1.1(+) cells. Our results suggest that fibroblasts can be genetically
      modified into efficient antigen-presenting cells for the induction of antigen
      specific CTL response in cancer immunotherapy.

PMID- 10897052
TI  - Pre-natal and peri-natal exposures and risk of testicular germ-cell cancer.
AB  - The present case-control study was undertaken to investigate the association
      between exposure to maternal hormones and risk of testicular germ-cell cancer by
      histologic subgroups. Cases were males, aged 16 to 59 years, diagnosed with
      testicular germ-cell cancer in Ontario between 1987 and 1989. Histologic review
      was performed on all eligible cases for the purpose of categorizing cases as
      seminoma or non-seminoma (the latter classified 2 ways, with and without tumors
      containing seminoma). Risk factor data were collected on 502 cases, 346 case
      mothers, 975 age-matched controls, and 522 control mothers. Exogenous hormone
      exposure was associated with elevated risk (OR = 4.9, 95% CI 1.7-13.9). Several
      additional risk factors were associated with risk of testicular cancer: bleeding
      and threatened miscarriage (OR = 0.6, 95% CI 0.3-1.0), maternal cigarette smoking
      (12+ cigarettes/day OR = 0.6, 95% CI 0. 4-1.0). pre-term birth (OR = 1.6, 95% CI
      1.0-2.5), and treatment for undescended testicle (OR = 8.0, 95% CI 3.2-20.0).
      First births were associated with elevated risk (OR = 1.7, 95% CI 1.0-2.8) among
      mothers below the age of 24 years at conception. There was little evidence that
      risk factors differed by histologic subgroup. We found evidence that exposure to
      maternal hormones, particularly estrogens, is associated with testicular germ
      cell cancer risk. Not only does exposure to elevated levels (exogenous hormone
      use, pre-term birth, and first births among young mothers) increase risk but also
      exposure to relatively lower levels (heavy cigarette consumption and, perhaps,
      bleeding and threatened miscarriage) may decrease cancer risk.

PMID- 10897051
TI  - A polymorphism in the CYP17 gene is associated with prostate cancer risk.
AB  - CYP17 encodes the enzyme cytochrome P-450c17 alpha, which mediates both 17 alpha
      hydroxylase and 17,20-lyase in the steroid biosynthesis pathway. A polymorphism
      in the 5; promoter region of the CYP17 gene has been described. Steroid hormones,
      especially androgens, are believed to play a key role in the etiology of prostate
      cancer. Therefore, polymorphisms in genes involved in the androgen metabolism may
      affect the risk of prostate cancer. We conducted a case-control study of 63
      patients with untreated histologically proven prostate cancer and 126 age-matched
      control men with benign prostatic hyperplasia (BPH) to determine whether a
      polymorphism in the CYP17 gene is associated with prostate cancer risk. This
      polymorphism was investigated by PCR/RFLP using DNA from lymphocytes. The
      transition (T-->C) in the risk allele (A2) creates a new recognition site for the
      restriction enzyme MspAI, which permits designation of the wildtype (A1) and the
      risk allele (A2). The prevalence of the A2/A2 genotype was significantly higher
      (P = 0.03) in the cancer group (23.8%) than in the BPH control group (9.5%). We
      found an increased risk in men carrying 2 A2 alleles (OR = 2.80, 95%CI = 1.02
      77.76). For carrier with at least 1 A2 allele, the OR was 0.90 (95%CI = 0.43
      1.89). After stratification by median age (66 years) at time of diagnosis, a
      marked increased risk was found in carriers of the A2/A2 genotype older than 66
      years (OR = 8.93, 95%CI = 1.78-49.19, P = 0.01). Although the sample size is
      rather small and the controls are BPH patients, our results suggest that the
      CYP17A2/A2 genotype may be a biomarker for prostate cancer risk, especially for
      older men.

PMID- 10897053
TI  - Diet, metabolic polymorphisms and dna adducts: the EPIC-Italy cross-sectional
      study.
AB  - DNA adducts in peripheral leukocytes are considered a reliable indicator of
      internal dose exposure to genotoxic agents and, possibly, of cancer risk. We
      investigated their association with diet and other individual characteristics in
      healthy adults. The prospective study EPIC-Italy, a section of a larger European
      project, enrolled 47,749 men and women, aged 35-64 years, in 5 centres: all
      provided individual information about dietary and life-style habits and a blood
      sample. In a cross-sectional study, approximately 100 volunteers were randomly
      selected from each of the three main geographical study areas (Northern, Central
      and Southern Italy). DNA adducts and four polymorphic metabolic genotypes were
      determined in peripheral leukocytes by using (32)P-postlabelling technique and
      PCR methods. Among 309 subjects (153 men), 72.8% had detectable levels of DNA
      adducts (mean: 8.1 +/- 0.6 per 10(9) nucleotides). Strong negative associations
      emerged with the reported frequency of consumption of fresh fruit and vegetables,
      olive oil, and the intake of antioxidants. DNA adducts were higher in subjects
      with GSTT1 null genotype (p = 0.05). Significant differences between study
      centres emerged in multivariate analyses (mean levels: 11.0, 10.0, 7.2, 6.5 and
      5.2 for Florence, Naples, Turin, Varese and Ragusa, respectively). A possible
      opposite seasonal variation was found according to latitude: adduct levels tended
      to be lower in winter in Florence and the southern centres, and during summer in
      the two northern centres. Frequent consumption of fresh fruit and vegetables is
      associated with reduced levels of DNA adducts, possibly contributing to the role
      of diet in modulating cancer risk.

PMID- 10897054
TI  - Increased risk of head and neck cancer in association with GSTT1 nullizygosity
      for individuals with low exposure to tobacco.

PMID- 10897055
TI  - No evidence for fibroblast growth factor receptor 3 (FGFR-3) R248C/S249C
      mutations in human prostate cancer.

PMID- 10897056
TI  - International Symposium on Biology of Cancer Prevention and Treatment: meeting
      report.

PMID- 10897057
TI  - Predictive value of the ultrasensitive HIV viral load assay in clinical practice.
AB  - The aim of this study was to determine whether an HIV viral load of <50 copies/ml
      (c/ml), in the first available plasma sample to have shown a viral load of <400
      c/ml, in patients on antiretroviral therapy, is correlated with longer term
      suppression of viral load (at <400 c/ml) compared to a viral load of 50-399 c/ml,
      and secondly, to compare the results obtained by ultrasensitive and standard
      viral load assays carried out on the same sample. A total of 98 HIV-positive
      patients on antiretroviral therapy with a viral load of <400 c/ml and at least
      one subsequent viral load measurement, were selected. For each patient, the first
      available specimen showing a viral load of <400 c/ml was tested using the Roche
      Amplicor ultrasensitive viral load assay, and patients were followed up
      subsequently for a median period of 52 weeks. Whether patients achieved an
      ultrasensitive viral load (USVL) of <50 c/ml or not made very little difference
      to the proportion of patients in each group showing continued response to
      treatment (52% vs. 45% respectively). The only variable that was shown to
      significantly predict longevity of response was the number of antiretroviral
      drugs used. Secondly, a standard viral load of <400 c/ml but with a detectable
      signal above background levels, was strongly predictive of a USVL of >50 c/ml.
      Overall, the findings suggest that the advantage in predictive value of the
      ultrasensitive over the standard HIV viral load assay, shown previously in
      clinical trials, may be limited in clinical practice.

PMID- 10897058
TI  - Accuracy of plasma HIV RNA quantification: a multicentre study of variability.
AB  - Inaccurate quantification of plasma HIV RNA concentration may be detrimental to
      patient care, yet little is known about how reproducible results are within and
      between laboratories. Each week between January and April 1998 a different
      laboratory represented at the Public Health Laboratory Service HIV Diagnosis
      Forum sent aliquots of the same anti-HIV positive plasma specimen by First Class
      Mail to the other 12 laboratories and to itself. Aliquots were frozen on receipt
      and examined in the next assay run. At the end of the 13 week period each
      laboratory reported their findings and provided further information about the
      specimen that they had dispatched. The correlation of results between
      laboratories and between the four different assay kits used was generally
      satisfactory. HIV RNA concentrations determined by the Roche Monitor and AcuGen
      kits were higher, and by the Chiron Quantiplex v 2.0 kit lower, than average. The
      Chiron Quantiplex gave the most reproducible concentrations. Nine 'below
      detection limit' results occurred, associated with three specimens. One specimen
      gave a below detection limit result in every one of six laboratories using the
      Organon Teknika Nuclisens HIV-1 QT kit, and was found to contain viral RNA of HIV
      1 clade G. Another below detection limit result was probably due to technical
      error, and the remaining two to assay insensitivity. The findings suggested that
      an unsustained change in HIV RNA of <log(10)1.00 may not be a reliable basis for
      modifying treatment. This study confirms the need for performance assessment and
      for conservative interpretation of isolated changes in the estimate of HIV RNA
      concentration. Parallel testing of consecutive specimens from individual
      patients, though expensive, probably offers the best indication of significant
      change in the HIV RNA concentration.

PMID- 10897059
TI  - Analysis of a human immunodeficiency virus type 1 gag mutant with an engineered
      110-amino-acid insertion in the matrix protein domain.
AB  - A human immunodeficiency virus (HIV) matrix (MA) protein mutant was constructed
      by duplication of 107 codons of the HIV-1 MA domain. This MA protein duplication
      mutant (MAII) still could assemble and process particles, had a wild-type (wt)
      HIV particle density, and possessed reverse transcriptase activity of about 80%
      of the wild type virus level. The incorporation of HIV Env and viral RNA genome
      was not greatly affected. The MAII was noninfectious or poorly infectious,
      however, when pseudotyped with an amphotropic murine leukemia virus envelope
      protein or with the HIV envelope protein. Although the MAII mutant displayed an
      immunofluorescence staining pattern similar to that of the wild type virus,
      subcellular fractionation studies indicated that the membrane association of MAII
      Gag precursors was unstable under high-salt conditions. Electron microscopic
      studies showed that the mutant had a decreased density of particle cores compared
      with that of the wild type virus, suggesting an altered arrangement of the packed
      proteins. As this insertion in the MA gene caused no major effects on virus
      assembly implies that the HIV-1 gag has the potential to adapt large insertions
      of extra coding sequences without loss of the ability to direct particle assembly
      and release.

PMID- 10897060
TI  - Dynamic study of HBsAg and HBeAg in saliva samples from patients with hepatitis B
      infection: diagnostic and epidemiological significance.
AB  - Analysis of 505 cases history of patients among men with viral hepatitis
      demonstrates that HBV infected patients represent 68.9% of the total and that a
      non-parenteral rate of transmission is the most likely means of hepatitis B
      infection. Saliva and serum testing for the presence of specific HBV markers
      (HBsAg, HBeAg and HBV DNA) at different phases of the infection process were
      carried out to review the diagnostic and epidemiological value of saliva samples
      from patients with acute viral hepatitis B. The frequency of HBsAg detection by
      Enzyme Immune Assay (EIA) in saliva of patients in acute period was found to
      correlate with the frequency of its detection in serum. In early convalescence
      the frequency of detection of that antigen in serum (59.5% of patients) was
      significantly higher than in saliva (23.8%) (P < 0.001). The frequencies of HBeAg
      detection by EIA in saliva samples was significantly higher than that in serum
      samples in both acute phase (84.3% and 28.1% of patients, respectively) and in
      early convalescence (56.2% and 3.1% of patients, respectively). The study of
      frequencies of detection of these antigens in the dynamics of the disease up to
      the total recovery of patients (observations were carried out for the period of
      60 days and longer) showed that in most patients there was a faster disappearance
      HBsAg from saliva than from serum. By the end of second month this antigen was
      detected in saliva of only 8.3% of patients whereas in serum in the same period
      HBsAg was detected in 33.3% of patients. HBeAg became undetectable in blood
      whereas HBs-antigenemia was still pronounced, and a month after the beginning of
      the disease it was not found in serum specimens. In saliva, HBeAg was detected in
      95.8% of patients observed directly after admission. A month after the beginning
      of the disease it was detected in saliva of 66.7% of patients and, by the end of
      observation period, in 12.5% of patients recovered from viral hepatitis. HBV DNA
      revealed by PCR in saliva and serum of HBV-infected patients was detected in
      acute period not only in serum (84.6% of cases) but also in saliva (46.2% of
      cases). The data illustrate the diagnostic value of saliva and point to the
      possible role of saliva as a source of HBV infection.

PMID- 10897061
TI  - Combination therapy with interferon-alpha plus N-acetyl cysteine for chronic
      hepatitis C: a placebo controlled double-blind multicentre study.
AB  - A small pilot study in patients with chronic hepatitis C (HCV) infection
      suggested that antiviral treatment with interferon (IFN) plus N-acetyl cysteine
      (NAC) was more effective than treatment with interferon alone [Beloqui et al.
      (1993) Journal of Interferon Research 13:279-282]. An attempt was made to confirm
      this by performing a placebo-controlled double-blind study at 8 medical centres
      in Spain and Italy. One-hundred forty-seven patients with chronic HCV infection
      were investigated, 73 received 3MU IFN-alpha thrice weekly plus NAC 1800 mg daily
      and 74 received IFN alone. Treatment was continued for 6 months and patients were
      followed up for a further 6 months. Amongst patients receiving IFN plus NAC,
      sustained virological responses were observed in 5.5%, transient responses in 26%
      and non-response in 68.5%. The figures for patients receiving IFN only were 4.1%,
      24.3% and 71.6% respectively. Sustained virological response was significantly
      associated with non-type 1 genotypes (P = 0.045) and with low pre-treatment
      viraemia levels (P = 0.034). Biochemical response (serum ALT concentrations)
      correlated with virological outcome in 97% (n = 139) of cases. Patients who
      experienced a sustained virological response also showed reduction in the Knodell
      histological activity index. It is concluded that patients with chronic HCV
      infection are very unlikely to benefit from the addition of N-acetyl cysteine to
      conventional therapy with interferon-alpha.

PMID- 10897062
TI  - Recurrent hepatitis C after liver transplantation.
AB  - Cirrhosis due to hepatitis C is now the commonest indication for liver
      transplantation in Western Europe and in the United States. Graft reinfection is
      almost universal. The natural history of recurrent hepatitis C ranges from
      minimal damage to cirrhosis in a few months or years. Different virus and host
      immune factors are involved in the pathogenesis of hepatitis and are determinants
      of the outcome. The association between immunosuppression and severity of HCV
      recurrence is conflicting and remains to be evaluated fully. The treatment of
      recurrent HCV disease with IFN or ribavirin, as monotherapy, is ineffective.
      Preliminary results from combination therapy, however, are encouraging.
      Currently, a reasonable approach would be to treat patients with histological and
      clinical disease progression. New approaches for the prophylaxis of recurrent
      hepatitis C are under evaluation but whether this treatment will influence the
      severity of liver disease or the outcome of recurrence is still unknown.

PMID- 10897063
TI  - Detection of TT virus DNA in patients with liver disease and recipients of liver
      transplant.
AB  - TT virus (TTV) is transfusion-transmissible but its involvement in post
      transfusion hepatitis is uncertain. To investigate the potential association of
      TTV with liver diseases, the prevalence of TTV DNA was tested by semi-nested PCR
      in 113 carriers of hepatitis C virus (HCV), 10 patients with acute liver failure,
      11 patients with cryptogenic cirrhosis and 200 control blood donors. Thirty-seven
      of these patients underwent liver transplantation and were tested pre- and post
      transplantation. TTV DNA was semi-quantified in serial samples from seven
      patients with unexplained post-transplant hepatitis. TTV genotyping was performed
      on samples from 28 patients by sequence analysis. The prevalence of TTV DNA in
      blood donors was 1.5% and 17% in HCV infected haemophiliacs. In patients with
      acute or chronic liver disease or hepatitis, 6 to 27% prevalence was observed.
      After liver transplantation, the prevalence of TTV DNA increased from 16 to 46%
      (P < 0.01). In patients who developed unexplained hepatitis post-transplantation,
      TTV viraemia did not parallel ALT levels. TTV DNA either increased in titre or
      became detectable shortly after transplantation, suggesting that either TTV was
      transfusion-transmitted, or, more likely, that immunosuppression caused a
      recurrence of low level or undetectable TTV viraemia. TTV had considerable
      genomic diversity in the N22 region, corresponding to at least 4 genotypes.
      Genotype 2 was found in 14/28 patients.

PMID- 10897065
TI  - Diagnosis and surveillance of herpes simplex virus infection of the central
      nervous system.
AB  - Herpes simplex viruses (HSV) are responsible for neurological disorders that
      require rapid diagnostic methods and specific antiviral therapy. During 1997,
      1431 cerebrospinal fluid samples (CSF) collected from 1339 patients with
      neurological disorder presentations were processed for HSV detection. Eleven
      patients were positive for HSV, seven presenting with encephalitis (6/7 due to
      HSV1) and 4 with aseptic meningitis (4/4 due to HSV2). The incidence of HSV
      encephalitis was 2.33 cases / 10(6) inhabitants/year. Among encephalitis (HSV
      encephalitis) cases, 1 patient died due to the late implementation of antiviral
      therapy, and sequelae were observed in 4 cases. No sequelae were observed in
      aseptic meningitis cases. Four HSV encephalitis cases were monitored by PCR
      detection in CSF. Despite acyclovir therapy, PCR remained positive in CSF up to
      20 days in 2 cases. This result suggest that the antiviral treatment for HSV
      encephalitis should be monitored by PCR detection of HSV in CSF.

PMID- 10897064
TI  - Biliary excretion of TT virus (TTV).
AB  - A novel DNA virus (TT virus; TTV) was isolated from a patient with post
      transfusion hepatitis of unknown etiology. If TTV replicates in the liver, TTV
      may appear in the bile. In the present study, to clarify whether fecal-oral
      infection occur via biliary excretion, the presence of TTV DNA was assessed in
      paired serum and bile samples collected from 28 patients with obstructive
      jaundice without parenchymal liver disease. TTV DNA was detected by polymerase
      chain reaction (PCR) using semi-nested primers, and quantified by Real Time
      Detection PCR (RTD-PCR). The nucleotide sequence of isolates TTV DNAs was also
      determined and the sequences were compared between serum and bile samples. Among
      28 patients, 7 were positive for TTV DNA in both samples, and 3 and 2 were
      positive in serum and bile respectively. Of 7 patients positive for TTV DNA in
      both samples, the TTV DNA titer was higher in serum of 4 patients and in bile of
      1 patient. Among 7 patients positive for TTV DNA in serum and bile, 6 had the
      same sequence in both samples. Multiple distinct types of TTV DNA clones were
      isolated from serum in 2 patients and from bile in 4 patients. In conclusion, TTV
      DNA is detected frequently in bile from patients with obstructive jaundice,
      suggesting a fecal-oral route of infection and high prevalence of asymptomatic
      TTV carriers. TTV DNA was detected only in serum from some patients, suggesting
      that replication of TTV may occur in other organs as well as in the liver.

PMID- 10897066
TI  - Treatment with meliacine, a plant derived antiviral, prevents the development of
      herpetic stromal keratitis in mice.
AB  - Herpetic stromal keratitis is caused by ocular infection with herpes simplex
      virus type 1 (HSV-1) and constitutes a leading cause of human blindness. The
      effect of meliacine, an antiviral compound isolated from leaves of Melia
      azedarach L. that inhibits HSV-1 replication in vitro, was examined on
      experimental corneal HSV-1 inoculation in Balb/c mice. Mice were inoculated with
      HSV-1 strain KOS at their corneas after abrasion. Meliacine was administered
      topically 3 times a day for 4 days beginning 1 day before inoculation. Infected
      animals treated or not with meliacine were observed carefully for the development
      of stromal keratitis and the clinical scoring was done 14 days post-infection.
      Histological examination of corneas and viral isolation from eyes from HSV-1
      infected mice treated or not with meliacine were also carried out. It was found
      that the treatment of HSV-1-induced ocular disease in Balb/c mice with meliacine
      reduced significantly the development of clinical disease, as well as the
      histological damage in corneas. The viral titers detected in eyes of infected and
      treated mice were 2-orders-of-magnitude lower than those corresponding to HSV-1
      infected control animals. Mock-infected and treated mice did not reveal any
      corneal alteration due to the administration of the compound. Meliacine was found
      to exert a strong antiviral action on HSV-1-induced ocular disease in mice with
      no evidence of toxic effects.

PMID- 10897067
TI  - Human cytomegalovirus strains associated with congenital and perinatal
      infections.
AB  - The genotypes of human cytomegalovirus (HCMV) isolates from pediatric patients
      differs from those of infected adults in Australia. Genotypes were determined by
      PCR amplification of glycoprotein B (gB) sequences, with subsequent analysis by
      restriction fragment length polymorphism, single-stranded conformation
      polymorphism, heteroduplex mobility analysis and direct DNA sequencing.
      Restriction fragment length polymorphism analysis of gB showed genotypes gB1
      (39%) and gB3 (30%) were more prevalent in infected children and two new
      genotypes (gB6 and gB7) were found. Single-stranded conformation polymorphism was
      used to group isolates into 22 further subtypes and suggested longitudinal co
      infection or viral mutation was occurring over time. Heteroduplex mobility
      analysis was found to be the most accurate and concise of the four methods used
      for genotyping HCMV isolates. DNA sequencing was used to confirm the results
      obtained from heteroduplex mobility analysis, and identified two isolates that
      were incorrectly genotyped by restriction fragment length polymorphism analysis.
      Heteroduplex mobility analysis efficiently genotyped all samples and allowed
      estimation of sequence variation between isolates. These data suggest certain gB
      genotypes are associated more commonly with childhood infections, and these
      differ from strains associated with invasive disease in HIV patients.

PMID- 10897068
TI  - Cytomegalovirus cultured from different major leukocyte subpopulations:
      association with clinical features in CMV immunoglobulin G-positive renal
      allograft recipients.
AB  - Cytomegalovirus (CMV) cultured from peripheral blood mononuclear cells (PBMCs)
      was shown to be associated more closely with clinical manifestations than
      infectious CMV in polymorphonuclear leukocytes (PMNLs) of renal allograft
      recipients with secondary CMV infection. Shell vial culture was carried out with
      ficoll-purified PBMCs and PMNLs of 71 CMV IgG-positive patients after kidney
      transplantation. Thirty-six patients experienced active CMV infections. Of these,
      17 developed clinical symptoms. The diagnostic value of PMNLs and PBMCs viremia
      was determined in comparison to pp65 antigenemia, leukoDNAemia, plasma DNAemia,
      and detection of cytomegalic endothelial cells. In both PMNLs and PBMCs (with or
      without detectable endothelial cells), frequencies and levels of viremia were
      significantly higher among symptomatic patients. Regarding the occurrence of
      clinical CMV manifestations, the sensitivity of culture from PMNLs and from PBMCs
      fractions was 100%. Viremia in PBMCs, however, was far more specific (94%) than
      in PMNLs (74%). Cutoff values established previously for pp65 antigenemia and
      leukoDNAemia, standard markers in the laboratory, had similar specificity (96%
      each) to PBMCs viremia, but were less sensitive (88% each). Plasma DNA-emia was
      both less sensitive (82%) and less specific (69%) than PBMCs viremia. Detection
      of endothelemia showed maximal specificity (100%), but inferior sensitivity
      (47%). All patients had PBMCs viremia before the onset of symptoms. In
      conclusion, infectious CMV present in PBMCs may prove to be a determinant of
      clinical CMV manifestations in seropositive immunocompromised individuals.
      Factors involved in PBMCs tropism may help to understand the pathogenetic
      mechanisms of CMV dissemination in this group of patients.

PMID- 10897069
TI  - Oka varicella vaccine is distinguishable from its parental virus in DNA sequence
      of open reading frame 62 and its transactivation activity.
AB  - When the nucleotide sequences of the Oka vaccine and its parental varicella
      zoster virus (VZV) were compared in 6 open reading frames (ORFs), glycoprotein C
      (gC) and 5 transactivator genes, mutations were detected only in the immediate
      early gene 62. The vaccine virus contained a mixture of different sequences that
      had variations at 15 nucleotide positions, but only one sequence was found for
      the Oka parental virus gene 62. The Oka vaccine virus gene 62 could be
      distinguished from the parental virus gene using a simplified restriction-enzyme
      fragment length polymorphism analysis, using NaeI and BssHII. This analysis was
      based on the sequence data obtained in this study. Studies of the regulatory
      activities of the ORF62 gene product (IE62) in a transient transfection assay
      indicated that IE62 of the parental virus had a stronger transactivational
      activity than that of the vaccine virus in activating immediate-early, early, and
      late gene promoters. These data suggest that IE62 might play an important role in
      the attenuation of VZV.

PMID- 10897070
TI  - Genomic and antigenic variation among rotavirus strains circulating in a large
      city of Argentina.
AB  - Knowledge of the antigenic diversity of rotaviruses circulating in a region
      should be acquired before introducing a rotavirus vaccine. In a collection of 151
      rotavirus-positive samples from Mendoza, Argentina, strain diversity was
      evaluated utilizing G-typing monoclonal antibodies (MAbs), reverse-transcriptase
      polymerase chain reaction (RT-PCR) G and P typing, and electropherotyping (PAGE).
      The G type of 137 (91%) specimens was determined. Typing MAb reactivity with the
      homologous type ranged from 25-94%. For the seven G1 MAbs utilized, 28 patterns
      of reactivity among 68 G1 strains occurred. For the 48 G2 strains, six patterns
      of reactivity occurred utilizing three G2-specific MAbs. Of the 92 samples G- and
      P-typed by reverse-transcriptase-polymerase chain reaction, 89% had single G/P
      combinations: eight G1[P4], one G1[P6], twelve G1[P8], 58 G2 [P4], and two G2
      [P6]. Nine samples had more than one G type with a single P type, one sample had
      two P types associated with one G type, and one sample contained multiple G and P
      types. Twenty-nine PAGE patterns occurred for all G types, but differences of
      antigenic reaction did not predict differences in migration of gene segments 7,
      8, and 9. For three specimens showing discordant results between G type by enzyme
      linked immunosorbent assay (EIA) and RT-PCR, we observed unexpected
      electropherotypes. Complementary evaluation by RT-PCR and MAb-based EIA with
      multiple typing MAbs revealed genetic and antigenic diversity of circulating
      rotaviruses, including extensive intratypic variation of the G1 and G2
      neutralization antigens, in Mendoza during a single season of rotavirus activity.

PMID- 10897071
TI  - Characterisation of rotavirus G9 strains isolated in the UK between 1995 and
      1998.
AB  - G9P[6] and G9P[8] rotavirus strains were identified during 1995/96 through the
      molecular epidemiological surveillance of rotavirus strains circulating in the UK
      between 1995 and 1998. An increase in the incidence and spread of sporadic
      infections with rotavirus genotype G9P[8] across the UK was detected in the two
      following seasons. Partial sequencing of the VP7 gene showed that all the UK
      strains shared a high degree of homology and were related very closely to G9
      strains from the US and from symptomatic infections in India (> or =96%
      homology). The UK strains were related more distantly to the apathogenic Indian
      strain 116E (85-87.8% homology). Phylogenetic analysis revealed clustering of the
      UK strains into 3 different lineages (I to III) and into two sub-lineages within
      lineage I. There were correlations between VP7 sequence clustering, the P type
      and the geographical origin of the G9 strains. Partial sequencing of the VP4 gene
      showed high degree of homology (>98%) among all the P[6] strains, and the
      sequences obtained from the P[8] strains clustered into 2 of the 3 global
      lineages described for P[8] strains associated with other G types. These data
      suggest that G9 strains may be a recent importation into the UK, and that G9P[8]
      strains may have emerged through reassortment in humans between G9P[6] strains
      introduced recently and the more prevalent cocirculating G1, G3 and G4 strains
      that normally carry VP4 genes of P[8] type.

PMID- 10897072
TI  - Cytokine profiles in heart, spleen, and thymus during the acute stage of
      experimental coxsackievirus B3-induced chronic myocarditis.
AB  - Since cytokines play an important role in the pathogenesis of virus-induced
      chronic heart diseases, cytokine mRNA expression was studied in coxsackievirus B3
      infected NMRI mice during the acute phase of myocarditis until the onset of
      chronic cardiac disease. Virus replication, cytokine induction, inflammatory cell
      infiltration and myocardial damage were studied by titer determination, reverse
      transcription-polymerase chain reaction (RT-PCR), and histopathology. To
      investigate whether the coxsackievirus B3-induced cytokine mRNA accumulation was
      only limited to the heart or generalized, spleen and thymus specimens were also
      included. Surprisingly, interleukin (IL)-10 as a deactivator of T cell and
      macrophage functions was transcribed in the myocardium nearly in parallel with
      virus replication from Day 1 through Day 14. At Day 3 p.i., the mRNA of IL
      1alpha, tumor necrosis factor (TNF)-alpha, IL-6, and interferon (IFN)-beta
      accumulated. At Days 4, 7, and 14, IL-12-specific mRNA was produced. Furthermore,
      increasing amounts of IFN-gamma mRNA were found, whereas IL-2 and IL-4 mRNA
      remained undetectable. TNF-alpha, IL-1alpha, IL-10, IL-12, and IFN-gamma mRNA
      persisted into the late stage of myocarditis. In the spleen a closely correlated
      expression of virus and IL-10-specific mRNAs was also found, and in addition, IFN
      beta, TNF-alpha, and IL-6 were detected. In striking contrast to heart and spleen
      tissue, the distinct expression of viral RNA in the thymus was not accompanied by
      an increased cytokine mRNA production. These data provide evidence for a unique
      coxsackievirus B3-induced cytokine pattern in the myocardium and spleen and
      suggest that persistently expressed IL-10 may play a leading role in acute and
      chronic myocarditis by subverting the immune response.

PMID- 10897073
TI  - Detection of reverse transcriptase activity in the serum of patients with motor
      neurone disease.
AB  - The recognition that both human and murine retroviruses can cause motor neurone
      disease-like syndromes has raised the possibility that a retrovirus may be
      involved in the aetiology of motor neurone disease. This possibility was explored
      by looking for evidence of reverse transcriptase in the serum of motor neurone
      disease patients. Sera from 56 patients with motor neurone disease and 58
      controls were tested by the product-enhanced reverse transcriptase assay, a
      technique that is approximately a million fold more sensitive than conventional
      reverse transcriptase assays and capable of detecting very low numbers of
      retroviral particles. Cell-free reverse transcriptase activity was detected in
      the serum of 33 of the 56 motor neurone disease patients (59%) but in only 3 of
      the controls (P < 0.00001). The reverse transcriptase activity was detectable in
      the presence of a large excess of an effective inhibitor of human cellular DNA
      polymerases and was therefore tentatively considered to be compatible with a
      retroviral origin. The reverse transcriptase activity, however, was not found to
      be due to the presence of known human exogenous retroviruses including HIV-1, HIV
      2, HTLV-I, HTLV-II, HRV-5 or human foamy virus, as assessed by PCR-based assays.
      Further investigations will be required to determine the source of the reverse
      transcriptase activity observed in these motor neurone disease patient sera.

PMID- 10897074
TI  - Predictors of treatment outcome for binge eating disorder.
AB  - OBJECTIVE: The purpose of this study was to identify predictors of short-term
      treatment outcome for individuals with binge eating disorder (BED). METHOD: Fifty
      women who met DSM-IV criteria for BED were enrolled in a manual-based group
      cognitive-behavioral therapy that consisted of fourteen 1-hr sessions over an 8
      week period. Baseline measures included the frequency of self-reported binge
      eating from the Eating Behaviors-IV (EB-IV), severity of binge eating and dietary
      restraint using the Binge Eating Scale (BES) and Three-Factor Eating
      Questionnaire (TFEQ), depressive symptoms as assessed by the Beck Depression
      Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS), and self-esteem
      as measured by the Rosenberg Self-Esteem Questionnaire (RSEQ). RESULTS: Logistic
      regression analyses indicated that the baseline frequency of self-reported
      episodes of binge eating that were objectively large predicted the likelihood of
      such episodes at the end of treatment. No variables predicted the likelihood of
      binge eating episodes that were objectively and subjectively large at the
      conclusion of treatment. DISCUSSION: This study indicates that the frequency of
      binge eating episodes at baseline is predictive of outcome status at the end of
      treatment, suggesting that meaningful prognostic factors in BED are identifiable.

PMID- 10897076
TI  - Relationship of temperament and perceptions of nonshared environment in bulimia
      nervosa.
AB  - OBJECTIVE: Examine the relationship between temperament variables and perceptions
      of nonshared environment as they relate to bulimia nervosa. METHOD: Fifty-seven
      adult women completed the Tridimensional Personality Questionnaire and the
      Sibling Inventory of Differential Experience. These measures provided assessments
      of frequently studied temperament traits as well as nonshared environmental
      factors believed to be associated with psychopathology and temperament. RESULTS:
      Bulimic subjects showed higher levels of harm avoidance than did control
      subjects. Also, bulimic subjects perceived their fathers as less affectionate and
      more controlling than control subjects. Among bulimics, high levels of harm
      avoidance were associated with high levels of maternal affection and low levels
      of maternal control. Similarly, among bulimics, high levels of novelty seeking
      were more likely to be associated with decreased paternal control than was true
      for control subjects. DISCUSSION: These findings highlight the possible
      relationship between particular temperamental variables and associated family
      responses in bulimia nervosa.

PMID- 10897075
TI  - Outcome of anorexia nervosa: eating attitudes, personality, and parental bonding.
AB  - BACKGROUND: We examined eating attitudes, personality, and parental bonding in
      women with a history of anorexia nervosa stratified by degree of recovery in
      comparison to randomly selected controls. We were interested in the
      distinguishing characteristics of recovery and of chronic anorexia nervosa.
      METHOD: All female new referrals to an eating disorders service between January
      1, 1981 and December 31, 1984 with probable or definite anorexia nervosa were
      eligible for inclusion. 86.4% of these women ("cases") were located and agreed to
      participate. The control group was a random community sample. All subjects were
      interviewed with a structured diagnostic instrument and completed a battery of
      psychological inventories including the Eating Disorder Inventory (EDI), the
      Three-Factor Eating Questionnaire (TFEQ), the Temperament and Character Inventory
      (TCI), and the Parental Bonding Instrument (PBI). RESULTS: We divided the
      anorexia follow-up sample into full recovery (n = 21), partial recovery (n = 34),
      and chronically ill (n = 15) and compared them to community controls (n = 98).
      The chronically ill group was distinguished by a lower desired body mass index
      (BMI), higher cognitive restraint on the TFEQ, higher Drive for Thinness and
      Bulimia on the EDI, lower maternal and paternal care on the PBI, and high harm
      avoidance and low self-directedness on the TCI. The full recovery group scored
      high on self-directedness and cooperativeness on the TCI. CONCLUSIONS: The
      domains of personality, character, and parental bonding differ among categories
      of recovery in anorexia nervosa. Whether these differences contribute to recovery
      or emerge during recovery or lack thereof remains an unanswered question.

PMID- 10897077
TI  - A prospective study of familial and social influences on girls' body image and
      dieting.
AB  - OBJECTIVE: This study examines the emergence of body image concerns and dieting
      behaviors in early adolescence as a function of girls' perceptions of family
      relationships, maternal modeling of dieting behaviors and body image concerns,
      and familial and peer pressures to diet. METHOD: Self-report measures were
      obtained from 77 White girls and their mothers in early adolescence (mean age =
      12.3 years) and 1 year later. RESULTS: Girls' perceptions of family relations and
      mothers' perceptions of daughters' weight at Time 1 significantly predicted
      girls' dieting behavior 1 year later over and above Time 1 dieting and body
      image. Only girls' previous body image and dieting behaviors significantly
      predicted more body dissatisfaction 1 year later. Girls' body image was found to
      mediate the relationship between family relations and dieting at Time 1
      assessment, but not over time. DISCUSSION: The importance of implementing early
      prevention and interventions programs is discussed.

PMID- 10897078
TI  - Cross-cultural explanations of body image disturbance in Western cultural
      samples.
AB  - OBJECTIVE: We replicated and extended the findings of S. M. Stormer and J. K.
      Thompson (1996), by comparing the relationships among body image disturbance
      (BID) and teasing history, age of pubertal onset, societal pressures to be thin,
      and appearance comparison, across three Western cultures. METHODS: College
      females from the United States, Italy, and England completed several BID
      measures, as well as measures of the four predictors. Body mass levels and self
      esteem, two known correlates of BID, were also examined. Data were analyzed using
      first standard, then hierarchical regression procedures. RESULTS: This
      investigation essentially found no cultural differences in the relationships
      among BID and its correlates for six of the seven criteria (BID) measures. Only
      one of the measures, the Figure Rating Scale (FRS), distinguished across groups.
      DISCUSSION: A lack of true cultural differences, or general similarities among
      university students, might explain these results. Nevertheless, these findings
      support the use of a Western cross-cultural research model.

PMID- 10897079
TI  - Prevalence of anorexia nervosa and bulimia nervosa in a geographically defined
      area in Japan.
AB  - OBJECTIVE: Little has been understood regarding the frequency of eating disorders
      in Japan. This study was designed to identify the prevalence of anorexia nervosa
      (AN) and bulimia nervosa (BN) in Japan. METHOD: We asked doctors in all of the
      relevant medical facilities (130 hospitals and 1,326 clinics) in Niigata
      Prefecture to report patients with DSM-IV-diagnosed eating disorders who appeared
      or were admitted between 20-24 October 1997. The response rate was 94.4%.
      RESULTS: The estimated point prevalences of AN and BN were 4.79 and 1.02,
      respectively, per 100,000 females. Specifically for the age group of 15-29 years,
      the prevalence of AN was 17.10 and that of BN 5.79. DISCUSSION: The prevalence of
      AN and BN in Japan is lower than that for European Caucasian populations. This
      result may be due to cultural and ethnic differences and/or it may be a transient
      phenomenon.

PMID- 10897080
TI  - Hypophosphatemia secondary to oral refeeding in anorexia nervosa.
AB  - OBJECTIVE: Hypophosphatemia is a well-known complication of the refeeding
      syndrome in severe cases of anorexia nervosa, described mostly as a result of
      refeeding with total parenteral nutrition. Few cases have been reported secondary
      to either nasogastric or oral refeeding. METHOD: The authors present three cases
      in which hypophosphatemia developed secondary to oral refeeding in severe
      anorexia nervosa. RESULTS: All 3 patients developed significant hypophosphatemia,
      to a low of 0.9 mg/dl in two cases and a low of 1. 7 mg/dl in the third. The
      first patient received close to 3,000 calories per day, along with intravenous
      fluids, in the hospital; the other 2 patients ate large amounts for several days
      at home. Caloric restriction and replenishment with phosphorous resulted in a
      rapid return of phosphorous values to normal levels. DISCUSSION: Those who treat
      severely malnourished patients with eating disorders, whether as inpatients or
      outpatients, need to be vigilant for the development of the refeeding syndrome,
      even in patients receiving oral refeeding alone.

PMID- 10897081
TI  - Development and validation of the Parental Intrusiveness Rating Scale among
      bulimic and comparison women.
AB  - OBJECTIVE: Based on hypotheses generated during clinical interviews with 80 women
      with a lifetime history of bulimia nervosa (BN), we designed an instrument for
      assessing the extent to which women with BN report parental intrusiveness and
      breakdown of appropriate role boundaries during their adolescent development.
      METHOD: Through an iterative process of item generation and scale administration,
      the Parental Intrusiveness Rating Scale (PIRS), consisting of 20 maternal items
      and 20 paternal items, was developed. Maternal subscales include Invasion of
      Privacy, Jealousy and Competition, and Overconcern with the Daughter's Eating,
      Weight, and Shape. Paternal subscales include Invasion of Privacy, Seductiveness,
      and Overconcern with the Daughter's Eating, Weight, and Shape. We validated the
      instrument using a subset of the above BN and comparison women (ns = 55 and 33,
      respectively), as well as an independent sample of women with BN and college
      comparison subjects (ns = 31 and 540, respectively). RESULTS: Parental
      intrusiveness scores were significantly positively correlated with disturbed
      relationships in the family of origin of our initial cohort. Reliability
      analyses, both test-retest and item-scale correlations, revealed adequate to
      strong statistical associations in the combined sample. CONCLUSION: The PIRS
      promises to enrich our understanding of problematic parental behaviors among
      women who develop BN and allows us to broaden the conceptualization of familial
      risk factors for this disorder.

PMID- 10897082
TI  - Parental intrusiveness in adolescence recalled by women with a history of bulimia
      nervosa and comparison women.
AB  - OBJECTIVE: To learn if women with a lifetime history of bulimia nervosa (BN)
      report more intrusive parental behavior during adolescence than their nonclinical
      peers, and to provide further validation of the Parental Intrusiveness Rating
      Scale (PIRS). METHOD: We administered the PIRS to 86 women with a lifetime
      history of BN and 573 comparison subjects and examined between-group differences.
      RESULTS: Relative to the comparison group, lifetime BN subjects reported higher
      levels of parental intrusiveness, specifically maternal invasion of privacy,
      maternal jealousy and competition, paternal seductiveness, and maternal and
      paternal overconcern with the daughter's eating, weight, and shape. There were no
      between-group differences in paternal invasion of privacy. In exploratory
      analyses with the comparison sample, Caucasian women reported greater maternal
      jealousy and competition than Asian American/Pacific Islander women, but there
      were no other differences. CONCLUSION: These results support clinical
      observations of high levels of parental intrusiveness in the adolescent
      experiences of women who develop BN. Nonclinical women of diverse ethnic
      backgrounds report largely equivalent experiences.

PMID- 10897083
TI  - Why the high rate of dropout from individualized cognitive-behavior therapy for
      bulimia nervosa?
AB  - OBJECT: To investigate predictors of dropout from cognitive-behavior therapy for
      bulimia nervosa. METHOD: Pretreatment assessment measures were examined including
      the Eating Disorder Inventory-2, Body Satisfaction Questionnaire, Beck Depression
      Inventory, Beck Hopelessness Scale, the Locus of Control of Behavior Scale, and
      demographic and behavioral measures. RESULTS: Forty-three percent (n = 14) of
      clients with a DSM-IV diagnosis of bulimia nervosa dropped out of treatment
      prematurely. No differences were found between treatment completers and dropouts
      with respect to the initial severity of bulimia-related symptoms. Noncompleters
      were, however, found to have significantly higher depression and hopelessness
      scores as well as elevated levels of external locus of control. Discriminate
      analysis showed that these variables resulted in a 90% prediction accuracy of
      individuals who prematurely dropped out of treatment. DISCUSSION: Results suggest
      a need to focus treatment directly on factors such as hopelessness and depression
      in addition to standard bulimia procedures to ensure clients are able to engage
      in therapy.

PMID- 10897084
TI  - Film-induced sadness as a trigger for disinhibited eating.
AB  - OBJECTIVE: We tested whether film-induced sadness enhances food intake in
      restrained eaters. METHOD: Female participants scoring either high or low on a
      measure of dietary restraint viewed two film segments in counterbalanced order on
      successive days: an emotionally neutral travelogue and a sad film depicting the
      death of the young female protagonist. RESULTS: Contrast analyses revealed that
      film-induced sadness significantly reduced food intake in low-restraint
      individuals, but only nonsignificantly increased it in high-restraint
      individuals. DISCUSSION: When sadness is induced without an apparent ego threat,
      high-restraint participants may not exhibit as much disinhibited eating as when
      they are exposed to mood inductions that threaten their self-esteem.

PMID- 10897085
TI  - The emergence of dieting among female adolescents: age, body mass index, and
      seasonal effects.
AB  - OBJECTIVE: The purpose of this brief report is to document the emergence of
      dieting in adolescent girls across a 2-year period, and to establish whether the
      changes in dieting status were related to the girls' age, body mass index, or to
      seasonal effects. METHOD: As part of a large-scale longitudinal study concerned
      with adolescent health and well-being, 478 girls, initially aged 12 to 16 years
      old, completed Strong and Huon's (Eating Disorders 5:97-104, 1997) dieting status
      measure on four separate occasions across a 2-year period. RESULTS: A total of
      273 girls (57.1%) identified themselves as nondieters when we first visited their
      school. Of those, approximately 20% indicated that they had begun to diet on one
      of the subsequent testing occasions. The emergence of dieting was observed to
      occur more in the 13- and 14-year-olds than in any other age group. Higher body
      mass index was not associated with the initiation of dieting as some underweight,
      and even very underweight girls, began to diet. DISCUSSION: The emergence of
      dieting occurs in early adolescence and might be triggered by concerns about
      changes in body shape.

PMID- 10897086
TI  - Initiation of dieting among adolescent females.
AB  - OBJECTIVE: This brief report identifies the factors that distinguish girls who
      have begun dieting recently from those who have never dieted, using Huon and
      Strong's (International Journal of Eating Disorders 23:361-369, 1998) model of
      dieting. METHOD: Sixty-two initiating dieters were carefully matched with 62
      never dieters, according to school, grade, age, language spoken at home, and
      country of birth. Both groups completed a battery of questionnaires that assessed
      their dieting status, perceived social influence to diet, conformity disposition,
      assertiveness, and familial context. RESULTS: A discriminant function analysis
      showed that initiating dieters and never dieters could be distinguished most
      clearly by their levels of peer and parental influence. Initiating dieters
      conformed and complied more to their parents. They were also more competitive
      with their peers than were the girls who had never dieted. Perceived
      supportiveness of fathers was also found to set apart those girls who had never
      dieted. DISCUSSION: Girls who are just beginning to diet differ from those who
      have never dieted, predominantly in terms of their perceived social influence.
      The forms of parental influence that distinguish the two groups differ in nature
      from the type of influence exerted by peers.

PMID- 10897087
TI  - Resting energy expenditure and plasma leptin levels in anorexia nervosa during
      acute refeeding.
AB  - OBJECTIVE: To examine changes in plasma leptin levels and resting energy
      expenditure (REE) during short-term refeeding of patients with anorexia nervosa
      (AN). METHOD: This was a longitudinal study of 21 women meeting the DSM-IV
      criteria for AN who were admitted to the hospital for renutrition. Height,
      weight, percent body fat (assessed by skin fold thickness), REE (measured by
      indirect calorimetry), and circulating plasma leptin concentration were assessed
      at the time of admission and 7 days later. RESULTS: Over the course of 1 week of
      refeeding, body mass index (BMI) increased 0.75 +/- 0.15 kg/m(2) (p <.0001), body
      fat increased 0.9 +/- 0.2% (p <.0001), and REE increased 107 +/- 33 kcal/24 hr (p
      =.0037). The change in mean leptin levels was not statistically significant (0.45
      +/- 0.44 ng/ml; p =.32). DISCUSSION: Leptin is unlikely responsible for the
      increase in REE observed with short-term refeeding.

PMID- 10897088
TI  - Cognitive content among bulimic women: the role of core beliefs.
AB  - OBJECTIVE: Most cognitive analyses of bulimic disorders have stressed the role of
      negative automatic thoughts or dysfunctional assumptions regarding weight, shape,
      and food. This study considered the role of more general core beliefs in the
      cognitive content of bulimic disorders. METHODS: Fifty bulimic and 50 comparison
      women completed the Schema Questionnaire (YSQ) and a diary measure of bulimic
      behaviors. RESULTS: The groups could be differentiated using just three of the
      beliefs: perceived Defectiveness/Shame, Insufficient Self-Control, and Failure to
      Achieve. This discrimination included differences between bulimic subgroups. At
      the symptomatic level, the bulimic women's Emotional Inhibition beliefs predicted
      their severity of binging, whereas their Defectiveness/Shame beliefs predicted
      severity of vomiting. CONCLUSIONS: The findings support a model of bulimic
      psychopathology where the central cognitions encompass more than beliefs about
      food, shape, and weight. Clinical implications are considered.

PMID- 10897089
TI  - Some correlates of dieting behavior in Saudi schoolgirls.
AB  - OBJECTIVES: The study examines the correlates of dieting behavior among Saudi
      schoolgirls. METHODS: Stratified cluster sampling was used to select female
      students from Grades 7 to 11 in Riyadh, Saudi Arabia. Subjects completed a
      sociodemographic data sheet and the Eating Disorders Inventory (EDI); their
      heights and weights were measured by a trained nurse. The total sample size was
      1,271 students with a response rate of 92.76%. RESULTS: 15.9% scored positively
      on the EDI-Drive for Thinness subscale. Body mass index, speaking a Western
      language, and having lived in a Western country were the most significant
      personal factors associated with dieting behavior. Small family size and higher
      parental education and better occupation were significant family factors
      associated with dieting. DISCUSSION: Results reflect some culture-specific
      findings that are explained in cultural terms.

PMID- 10897090
TI  - Correction

PMID- 10897091
TI  - A lysine rich C-terminal tail is directly involved in the toxicity of CSTX-1, a
      neurotoxic peptide from the venom of the spider Cupiennius salei.
AB  - CSTX-1 (74 amino acids, 8,352.62 Da) is a potent neurotoxin from the venom of
      Cupiennius salei. With the monoclonal antibody 9H3 against CSTX-1, we identified
      two similar peptides by Western blot analysis. These two peptides were purified
      by RP-HPLC: CSTX-2a (61 amino acids, 6865.75 Da) and CSTX-2b (60 amino acids,
      6709.57 Da). Using ESI-MS analysis and sequencing we verified that CSTX-2a is a
      truncated version of CSTX-1. CSTX-2b differs from CSTX-2a by the absence of
      Arg61. Toxicity of CSTX-1, CSTX-2a, and CSTX-2b to Drosophila melanogaster showed
      that the absence of the last 13 amino acids of CSTX-1 results in a seven-fold
      activity loss. CSTX-2b, which lacks Arg61 is 190-fold less toxic. We conclude
      that the C-terminal part of CSTX-1, especially Arg61, is essential for the
      expression of toxicity. CSTX-1 is degraded to CSTX-2a and CSTX-2b by proteases
      that are released from venom gland cells by apocrine secretion.

PMID- 10897092
TI  - Effects of developmental age, ambient temperature, and dietary alterations on
      delta(12) desaturase activity in the house cricket, Acheta domesticus.
AB  - Double bond formation in polyunsaturated fatty acids (PUFA) is mediated by
      desaturase enzymes. Certain insect species have been found to possess a Delta(12)
      desaturase, previously thought to occur exclusively in plants. We have begun to
      characterize this enzyme to determine its relatedness to those found in plants
      and animals. Desaturase activity can be altered significantly by a number of
      environmental factors in protozoa, cyanobacteria, plants, fish, and rats. We
      present evidence here that Delta(12) desaturase activity in Acheta domesticus is
      affected by developmental stage, starvation, dietary alterations, and
      fluctuations in ambient temperature. Highest activity is observed during the
      middle of the penultimate instar and 3 to 6 days after adult emergence.
      Starvation markedly decreases Delta(12) activity, whereas resumption of feeding
      on fat-free or low fat diets increases activity.

PMID- 10897093
TI  - Purification and molecular cloning of chemosensory proteins from Bombyx mori.
AB  - Soluble low molecular weight acidic proteins are suspected to transport stimulus
      molecules to the sensory neurons within insect sensilla. From the antennae of
      Bombyx mori, we have purified and sequenced a protein (BmorCSP1) bearing sequence
      similarity to a class of soluble chemosensory proteins recently discovered in
      several orders of insects. Based on its N-terminal sequence, the cDNA encoding
      this protein has been amplified and cloned. Differential screening of a B. mori
      antennal cDNA library led to the identification of a second gene encoding a
      related protein (BmorCSP2), sharing 35-40% identity to BmorCSP1 and chemosensory
      proteins from other species. The predicted secondary structures of moth's,
      chemosensory proteins comprise alpha-helical foldings at conserved positions and
      a reduced hydrophobicity with respect to this novel family of chemosensory
      proteins.

PMID- 10897094
TI  - Vitellin and vitellogenin in the soldier bug, Podisus maculiventris:
      identification with monoclonal antibodies and reproductive response to diet.
AB  - A 171,000 M(r )polypeptide of Podisus maculiventris (Say) (Heteroptera:
      Pentatomidae) that constituted 16% of the protein in eggs also constituted up to
      25% of the protein in hemolymph of fed females. It was identified as the major or
      sole apoprotein of vitellogenin. Eggs contained major polypeptides of 171, 106,
      and 51 kDa. The hemolymph polypeptide was identified with a polypeptide
      (vitellin) in egg extracts by comparing molecular weights, specificity of
      occurrence in fed females, and immunological reactivities. Females, starved for 5
      days after eclosion to assure complete previtellogenic development, produced
      vitellogenin within a day after feeding on larval Galleria mellonella, and within
      4 days after feeding on an artificial diet. Appearance of vitellogenin preceded
      ovarian growth by 2-3 days. Two monoclonal antibodies raised against egg proteins
      of P. maculiventris were selected for their strong reaction against egg extract
      and female hemolymph and null reaction against male hemolymph. Only one 170-kDa
      band in egg and hemolymph reacted with the antibodies on denaturing Western
      blots. These monoclonal antibodies are being used to develop an enzyme-linked
      immunosorbent assay (ELISA) to quantitate reproductive response of females to
      diets of differing quality.

PMID- 10897095
TI  - Demonstration of amylase from the zoophytophagous anthocorid Orius insidiosus.
AB  - To better understand facultative phytophagy in the zoophytophagous anthocorid,
      Orius insidiosus, tests for amylase were conducted and the enzyme was partially
      purified. Three activity bands were detected with polyacrylamide-starch gel
      electrophoretic analysis of amylase in O. insidiosus. The major amylase was found
      to have a mean isoelectric point (pI) of 4.53. The presence of amylase indicates
      the ability of O. insidiosus to use starch, a nutrient, derived from plants,
      either by direct ingestion or by ingestion of plant material from the digestive
      system of their prey. The presence of amylase suggests that these predators are
      more committed to plant feeding than other species of predators that lack this
      enzyme.

PMID- 10897097
TI  - Polar organic phase liquid chromatography with packed capillary columns using a
      vancomycin chiral stationary phase
AB  - Vancomycin immobilized on silica served as the chiral stationary phase (CSP) in
      this investigation with polar organic solvents as the mobile phase in liquid
      chromatography (LC). It was shown that trace amounts of water were beneficial for
      improving peak shape and efficiency. To regulate the retention and selectivity an
      acid and/or base were added to the mobile phase where an excess of acid was shown
      to be preferential for enantioseparation. An unusual increase in selectivity with
      increasing temperature was shown for the acidic drug, thalidomide. Additionally,
      nonlinear van't Hoff plots were obtained for metoprolol enantiomers that showed
      increased retention with increasing temperature. Metoprolol also showed unusual
      behavior in the polar organic phase when water was added to resemble reversed
      phase chromatography, with minimum retention observed at high water or high
      methanol concentrations. In both instances a high degree of electrostatic
      interaction between metoprolol and vancomycin was concluded. Metoprolol and ten
      of its analogs were examined on this CSP to evaluate the enantiorecognition
      process. A comparison in enantioselectivity for a number of acidic and basic
      drugs using this CSP was also carried out using the polar organic phase, reversed
      phase, and normal phase LC which were all compared to the results obtained in
      supercritical fluid chromatography (SFC). Polar organic phase LC offered a better
      separation of basic molecules while reversed phase LC was preferred for the
      resolution of acids. SFC showed the broadest enantioselectivity overall and
      normal phase LC indicated similar properties, as expected, to SFC but with lower
      column efficiency. Copyright 2000 Wiley-Liss, Inc.

PMID- 10897096
TI  - Stereospecific versus nonstereospecific assessments for the bioequivalence of two
      formulations of racemic chlorpheniramine.
AB  - Chlorpheniramine (chlorphenamine, CPAM) is a racemic antihistaminic H1 drug
      containing two enantiomers. The aim of this study was to assess the
      bioequivalence of two formulations (reference and Vietnamese-tested formulation)
      of racemic chlorpheniramine combined with phenylpropanolamine in an open-labeled,
      randomized, crossover two-period study, after administration of 8 mg of racemic
      chlorpheniramine in 12 healthy Vietnamese subjects. First, dissolution of both
      formulations was tested in vitro according to USP requirements. Then the 12
      subjects received both formulations after an overnight fast and a 7-day wash-out
      period. Plasma samples were collected up to 168 h. Plasma concentrations of total
      chlorpheniramine and its individual enantiomers were determined with a validated
      chiral HPLC method and pharmacokinetic parameters were estimated using model
      independent analysis. For the reference formulation, Cmax and AUC values were
      higher for (+)S-chlorpheniramine ((+)S-CPAM) compared to (-)R-chlorpheniramine ((
      )R-CPAM) (13.3 vs. 6.8 ng/ml and 409 vs. 222 ng/ml/h, respectively) while Clt/F
      and Vd/F were lower (9.8 vs. 17.6 l/h and 321 vs. 627 l, respectively). No
      difference was observed for Tmax, t(1/2), and MRT. Pharmacokinetic parameters
      were similar for the reference and the Vietnamese-tested formulation.
      Bioequivalence was assessed by Schuirmann test, as recommended by the current FDA
      and European Community criteria. Dissolution tests showed that both formulations
      were equivalent. A nonstereospecific, but not a stereospecific, approach
      indicated bioequivalence between the formulations.

PMID- 10897098
TI  - Optimization of lambda-carrageenan as a chiral selector in capillary
      electrophoresis separations.
AB  - Lambda-carrageenan, a linear high molecular weight sulfated polysaccharide, was
      employed as a chiral selector in capillary electrophoresis for the separation of
      enantiomers of weakly basic pharmaceutical compounds. In order to improve the
      utility of the chiral selector, the purity and concentration of the lambda
      carrageenan and other important capillary electrophoresis method parameters were
      investigated. The results indicated that the purity and concentration of the
      lambda-carrageenan, ionic strength of the buffer, and temperature were critical
      to successful enantioseparation. These new method conditions were then applied to
      previously investigated beta-blockers (such as propranolol HCl and pindolol) and
      racemic tryptophan derivatives. These studies were successful in identifying
      important method conditions for the improved enantioselectivity with lambda
      carrageenan.

PMID- 10897099
TI  - Optical resolution of alpha-alkyl phenyl acetonitriles by HPLC on cellulose
      triacetate chiral stationary phases coated on underivatized silica gel
AB  - Microcrystalline celluloses from two sources were used to prepare cellulose
      triacetate chiral stationary phases (CSPs) coated on underivatized silica gel,
      which shows discriminating chiral recognition for enantiomers. The chiral
      separation of four alpha-alkyl phenyl acetonitriles was investigated on the
      prepared CSPs. It was observed that the concentration of the coating solvent of
      phenol in dichloromethane plays an important role in the resolution of the
      solutes. A series of primary alcohols, including secondary and tertiary alcohols,
      were used as mobile phase modifiers to investigate the effect of the structures
      of these modifiers on the capacity factors (k') and the separation factors
      (alpha). Also, the effect of the concentration of alcohol on the capacity factors
      and separation factors was examined. The chiral recognition mechanism of alpha
      alkyl phenyl acetonitriles on the prepared CSPs is discussed. Copyright 2000
      Wiley-Liss, Inc.

PMID- 10897100
TI  - Separation of amino acid enantiomers by micelle-enhanced ultrafiltration.
AB  - A Micelle-enhanced ultrafiltration (MEUF) separation process was investigated
      that can potentially be used for large-scale enantioseparations. Copper(II)-amino
      acid derivatives dissolved in nonionic surfactant micelles were used as chiral
      selectors for the separation of dilute racemic amino acids solutions. For the
      alpha-amino acids phenylalanine, phenylglycine, O-methyltyrosine, isoleucine, and
      leucine good separation was obtained using cholesteryl L-glutamate and Cu(II)
      ions as chiral selector with an operational enantioselectivity (alpha(op)) up to
      14.5 for phenylglycine. From a wide set of substrates, including four beta-amino
      acids, it was concluded that the performance of this system is determined by two
      factors: the hydrophobicity of the racemic amino acid, which results in a
      partitioning of the racemic amino acid over micelle and aqueous solution, and the
      stability of the diastereomeric complex formed upon binding of the amino acid
      with the chiral selector. The chiral hydrophobic cholesteryl anchor of the chiral
      selector also plays an active role in the recognition process, since inversion of
      the chirality of the glutamate does not yield the reciprocal
      enantioselectivities. However, if the cholesteryl group is replaced by a
      nonchiral alkyl chain, reciprocal operational enantioselectivities are found with
      enantiomeric glutamate selectors.

PMID- 10897101
TI  - Beta-agonist-induced alterations in organ weights and protein content: comparison
      of racemic clenbuterol and its enantiomers.
AB  - Clenbuterol is a relatively selective beta2-adrenergic partial agonist that has
      bronchodilator activity. This drug has been investigated as a potential
      countermeasure to microgravity- or disuse-induced skeletal muscle atrophy because
      of presumed anabolic effects. The purpose of this study was to: 1) analyze the
      anabolic effect of clenbuterol's (-)-R and (+)-S enantiomers (0.2 mg/kg) on
      muscles (cardiac and skeletal) and other organs; and 2) compare responses of
      enantiomers to the racemate (0.4 mg/kg and 1.0 mg/kg). Male Sprague Dawley rats
      were treated with: a) racemic clenbuterol (rac-clenbuterol, 0.4 or 1.0 mg/kg); b)
      enantiomers [clenbuterol (-)-R or (+)-S]; or c) vehicle (1.0 mL/kg buffered
      saline). Anabolic activity was determined by measuring tissue mass and protein
      content. HPLC teicoplanin chiral stationary phase was used to directly resolve
      racemic clenbuterol to its individual enantiomers. In skeletal muscle, both
      enantiomers had equal anabolic activity, and the effects were muscle- and
      anatomic region-specific in magnitude. Although the enantiomers did not affect
      the ventricular mass to body weight ratio, clenbuterol (+)-S induced a small but
      significant increase in ventricular mass. Both clenbuterol enantiomers produced
      significant increases in skeletal muscle mass, while being less active in
      producing cardiac ventricular muscle hypertrophy than the racemic mixture.

PMID- 10897103
TI  - Editorial comment

PMID- 10897102
TI  - The role of panendoscopy in the management of mucosal head and neck malignancy-a
      prospective evaluation.
AB  - BACKGROUND: It is common practice for a panendoscopy to be included in the
      evaluation of patients with mucosal head and neck malignancies. Whether this
      intervention is efficient or cost-effective has not been established in our
      patient population. METHODS: Two hundred twenty-four patients with squamous cell
      carcinoma involving the oral cavity, pharynx, larynx, or neck were evaluated
      prospectively with panendoscopy and chest x-ray with or without barium swallow.
      One hundred fifty-four patients had newly diagnosed tumors and 70 were previously
      diagnosed and currently undergoing symptom-directed investigations. RESULTS: The
      incidence of synchronous primary tumors was 2.6% (4 of 154); pulmonary, 1.3%;
      head and neck mucosa, 1.3%; and esophageal, 0%. There was no associated
      morbidity. CONCLUSIONS: Although there was no associated morbidity, our head and
      neck oncology group is of the opinion that routine panendoscopy is not warranted.
      Specific indications for this investigation are discussed.

PMID- 10897104
TI  - Preoperative imaging to predict orbital invasion by tumor.
AB  - BACKGROUND: Our purpose was to examine the accuracy of preoperative imaging in
      assessing tumor invasion of the orbit and nasolacrimal system. METHODS: Nineteen
      preoperative CT and 17 preoperative MR images from patients at risk for orbital
      invasion were retrospectively reviewed. Invasion was corroborated by pathologic
      and intraoperative assessment. RESULTS: Tumor adjacent to the periorbita was the
      most sensitive predictor of orbital invasion (90%) for both CT and MRI.
      Extraocular muscle involvement on MRI (100%) and orbital fat obliteration (80%
      MRI, 86% CT) had the highest positive predictive values of the criteria
      evaluated. Extraocular muscle displacement and enhancement were less accurate
      (<65%) predictors. No one criterion was >79% accurate in predicting orbital
      invasion. Six or more positive criteria predicted invasion with 67% sensitivity
      and 80% specificity (accuracy, 72%). CT was more accurate than MRI in seven of
      nine criteria. Invasion of the nasolacrimal system was predicted accurately
      (89%). CONCLUSIONS: Although preoperative imaging can aid in surgical planning,
      it should not replace intraoperative assessment in ambiguous cases of orbital
      invasion.

PMID- 10897105
TI  - Use of the radial forearm fasciocutaneous free flap and montgomery salivary
      bypass tube for pharyngoesophageal reconstruction.
AB  - BACKGROUND: Head and neck reconstructive surgeons involved in pharyngoesophageal
      reconstruction have several options available to repair the defect after partial
      or total laryngopharyngectomy. There is no uniform agreement among head and neck
      surgeons as to which of the most frequently used techniques offers the best
      results. METHODS: A retrospective study was performed on 20 consecutive patients
      who had undergone reconstruction of the hypopharynx and cervical esophagus using
      a radial forearm free flap with Montgomery salivary bypass tube at the
      Massachusetts Eye and Ear Infirmary in Boston, Massachusetts, and St. Louis
      University, Department of Otolaryngology-Head and Neck Surgery between 1992 and
      1996. This reconstruction was used for primary reconstruction after total or
      partial laryngopharyngectomy with cervical esophagectomy, partial pharyngectomy
      sparing the larynx, and for reconstruction of the stenotic neopharynx after
      laryngectomy. RESULTS: The overall rate of pharyngocutaneous fistula was 20%, and
      the rate of postoperative stricture was 10%. Of patients reconstructed with this
      technique, 85% were able to resume oral alimentation, whereas 15% remained G-tube
      dependent. Of the 18 patients who did not have their larynges remain intact, 6
      were able to develop useful tracheoesophageal speech. CONCLUSIONS: The results of
      this study show that the radial forearm fasciocutaneous free flap in combination
      with the Montgomery salivary bypass tube is extremely useful for reconstruction
      of partial and circumferential defects of the hypopharynx and cervical esophagus.

PMID- 10897106
TI  - The role of fine-needle aspiration cytology in the management of parotid tumors:
      a critical clinical appraisal.
AB  - BACKGROUND: Fine-needle aspiration cytology (FNA) is a well-established tool for
      investigating many head and neck conditions. It application in parotid tumors is,
      however, very controversial. This article is aimed at defining the exact role of
      FNA in the diagnostic workup of patients. METHODS: A retrospective review of a 12
      years' experience in a university surgical unit of 186 consecutive patients.
      Clinical opinion, FNA results, and final pathologic findings were examined.
      RESULTS: FNA obtained the correct final pathologic condition in 54.3% of cases.
      It increased the identification of malignancy to 64.5% compared with 26% based
      solely on clinical signs. Malignant FNA diagnoses (85.7%) and repeatedly
      inconclusive reports (25.7%) were associated with a higher incidence of
      malignancy. CONCLUSIONS: Methodological interpretation of FNA results provides
      useful preoperative information and enables more reliable patient counseling and
      reduces pathologic surprises. Its enhancement of the preoperative recognition of
      malignant parotid tumors may alert more stringent attention to the operative
      margin and hence better tumor clearance.

PMID- 10897107
TI  - Pretreatment swallowing function in patients with head and neck cancer.
AB  - BACKGROUND: Few objective data characterizing the pretreatment swallow function
      of patients with head and neck cancer are available. METHODS: Pretreatment
      swallowing function in 352 patients with various lesions was evaluated with
      videofluoroscopy and compared with control subjects. RESULTS: Patients had
      significantly longer oral and pharyngeal transit times, greater amounts of oral
      and pharyngeal residue, shorter cricopharyngeal opening durations, and lower
      swallow efficiencies. Swallow function worsened significantly with increased
      tumor stage, and patients with oral or pharyngeal lesions had worse swallow
      function than patients with laryngeal lesions. Frequency of complaint of swallow
      difficulty before treatment was 59%. Patients with lower stage tumors had fewer
      complaints of swallowing, as did patients with oral cavity lesions. CONCLUSIONS:
      Despite demonstrating significant differences from control subjects, patients had
      highly functional swallows before treatment. The tendency for patients not to
      perceive a swallowing problem is consistent with the highly functional nature of
      their pretreatment swallow.

PMID- 10897108
TI  - Antisense inhibition of vascular endothelial growth factor in human head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent paracrine
      angiogenic factor involved in angiogenesis. We determined whether antisense VEGF
      transfection can suppress angiogenic activity of a human squamous cell carcinoma
      of the head and neck (SCCHN) cell line. METHODS: Human SCCHN cell lines were
      screened for VEGF secretion by ELISA. The highest VEGF secreting cell line was
      transfected with an antisense VEGF vector. Endothelial cell migration assays were
      performed using the conditioned medium from the transfected clones.
      Tumorigenicity assays of the transfectants in nude mice were also performed.
      RESULTS: Antisense VEGF expression exhibited a 20-fold inhibition of VEGF
      secretion. The addition of conditioned medium from the antisense clones resulted
      in 50% reduction of endothelial migration. There was no effect on in vivo
      tumorigenicity. CONCLUSIONS: Antisense VEGF transfection effectively down
      regulated VEGF secretion from SCCHN cells that had high VEGF secretion. Targeting
      VEGF expression may be useful for suppressing angiogenesis in head and neck
      cancer.

PMID- 10897109
TI  - Adenoid cystic carcinoma: use of cell proliferation, BCL-2 expression, histologic
      grade, and clinical stage as predictors of clinical outcome.
AB  - BACKGROUND: Although the three basic histologic growth patterns of adenoid cystic
      carcinomas (tubular, cribriform, and solid) provide some indication of clinical
      outcome, additional, perhaps superior, predictors of biologic activity are needed
      for patient management. METHODS: This series is composed of 31 adenoid cystic
      carcinomas that presented in Linkoping between 1982 and 1997. The tumors were
      clinically staged and histologically graded. For each case, after
      immunohistochemical identification, the proportion of tumor cells expressing the
      cell cycle markers MIB-1 and bcl-2 (as an indicator of proliferation and
      apoptosis, respectively) were quantified. Statistical correlation was sought
      between tumor stage and grade and the two cell cycle markers. RESULTS: The
      proportions of cycling tumor cells in adenoid cystic carcinomas ranged from 0.3%
      to 55%. For patients with no evidence of disease and a follow-up of at least 5
      years, the mean percent MIB-1 value was significantly lower than for those
      patients who were alive with local recurrence and/or metastasis or who had died
      from their adenoid cystic carcinoma (p =. 024). MIB-1 tumor cell positivity also
      correlated strongly with tumor grade (p =.053), but not with stage (p =.22).
      Neither clinical stage nor histologic grade correlated with the degree of bcl-2
      tumor cell positivity (p =.97 and p =.49, respectively). CONCLUSIONS: Staging and
      grading continue to play a vital role in the management of patients with adenoid
      cystic carcinoma. Furthermore, in this series of patients with adenoid cystic
      carcinoma, a cycling tumor cell population as measured by the MIB-1 antibody
      greater than 10% indicates this group as biologically more aggressive and at an
      increased risk for a fatal course.

PMID- 10897110
TI  - Urokinase receptor up-regulation in head and neck squamous cell carcinoma.
AB  - BACKGROUND: Urokinase-type plasminogen activator is important for matrix
      degradation and motility of cancer cells. For effective invasion, urokinase has
      to be associated with its cell surface receptor.(1) METHODS: We analyzed 33 head
      and neck squamous cell carcinomas (hnSCC) and 14 mucosal tissue samples for the
      expression of urokinase receptor using Northern hybridization and correlated
      expression levels to clinical and histopathologic data. Urokinase expression was
      determined by fibrin zymography. RESULTS: The expression of urokinase receptor is
      significantly increased in hnSCC compared with adjacent mucosa. Expression levels
      in primary tumors show no statistically significant correlations to T staging,
      metastasis, recurrence, or differentiation stage of the resected tumors.
      Furthermore, there was no correlation between urokinase and urokinase receptor
      expression levels in SCC samples. CONCLUSIONS: Urokinase receptor expression is
      increased in hnSCC, but it is not useful as a prognostic marker for the
      metastatic behavior of primary tumors. Comparison of our data with previously
      published reports is discussed.

PMID- 10897112
TI  - Weight characteristics of the parathyroid glands in renal hyperparathyroidism.
AB  - BACKGROUND: Although the mean weight of normal parathyroid glands is known,
      reports concerning the weight of hyperplastic glands in renal hyperparathyroidism
      are rare. The aim was to collect data about the weight of such glands and also to
      study the intraindividual distribution. METHODS: Statistical results are
      presented about the weight of 60 parathyroid glands that were removed in 20
      patients with renal hyperparathyroidism (the fourth gland was subtotally removed
      and therefore not included in the study). RESULTS: The median weight was 1.005 g,
      with a range from 0.10 to 7.15 g. All removed glands were enlarged, but the most
      salient finding was the wide distribution of weights. Also, the intra-individual
      variation was great. The largest gland of each patient weighed, on average, three
      to four times more than the smallest gland of the same subject. CONCLUSION: The
      weight of the superior glands tended to be somewhat greater in comparison with
      the inferior glands.

PMID- 10897111
TI  - Epstein Barr virus genome in nasopharyngeal carcinomas from New Zealand.
AB  - BACKGROUND: The population in New Zealand is a heterogeneous mix of Caucasians
      (80%), Maori (9%), and Polynesians (10%). It is believed that the Polynesians are
      of Chinese descent and may harbor the same high incidence of nasopharyngeal
      carcinoma (NPC). In addition, it is not known whether the Epstein-Barr virus
      (EBV) is as closely associated with the development of NPC in Polynesians as it
      is in those of Chinese origin. METHODS: This study reexamines the associative
      correlation between EBV and NPC with two methods of genetic detection, polymerase
      chain reaction (PCR) and in-situ hybridization (ISH). In addition, geographic
      heterogeneity was analyzed to determine whether there are differences in the
      prevalence of EBV in NPCs among the ethnic mixed populations found in New
      Zealand. Nasopharyngeal biopsy specimens from 20 patients with NPC and 36
      controls were obtained from Auckland. RESULTS: With PCR, EBNA-1, a genomic
      sequence of EBV in NPC samples was able to be detected with 76.5% sensitivity and
      96.7% specificity. By use of ISH, EBV was detected in NPC tissue with 82.4%
      sensitivity and 100% specificity. CONCLUSION: There seems to be no
      geoanthropologic differences in terms of the association of EBV with NPC.

PMID- 10897113
TI  - The contralateral bilobed trapezius myocutaneous flap for closure of large
      defects of the dorsal neck permitting primary donor site closure.
AB  - BACKGROUND: Various reliable local flaps can be used to cover soft tissue defects
      of the posterior neck. Among others, the (either vertical or transverse)
      trapezius myocutaneous flap is a reliable option in this context. However, for
      defects with a diameter larger than 15 cm, these flaps require skin grafting of
      the donor site. METHODS: To prevent this additional morbidity we describe a
      contralaterally based bilobed trapezius musculocutaneous flap successfully
      applied in two elderly patients with large tumors of the posterior neck in
      palliative situations. RESULTS: This novel approach makes use of a standard
      vertical skin paddle to cover the neck, together with a transverse cervical flap
      in a bilobed design to primarily close the paravertebral donor site. CONCLUSIONS:
      The bilobed technique allows the primary closure of massive soft tissue neck
      wounds. Preservation of the accessory nerve to the superior fibers of the
      trapezius muscle permitted normal arm elevation in our patients.

PMID- 10897114
TI  - Endoscopic laser surgery in the treatment of radiation failure of early laryngeal
      carcinoma.
AB  - BACKGROUND: This study was undertaken to analyze the local control rates and
      survival of patients undergoing endoscopic laser surgery for squamous cell
      carcinoma of the larynx as a salvage procedure for recurrent tumors after
      radiotherapy. METHODS: Twenty-four patients underwent endoscopic laser surgery
      for radiation failure at our hospital from 1988 to 1995. All patients were men,
      between 45 and 88 years old. The localization of the recurrence was in the
      supraglottis in 3 cases and in the glottis in 21 cases. The postirradiation
      recurrences were staged rT1 in 18 patients and rT2 in 6 patients. RESULTS: Local
      recurrence after laser surgery developed in six patients (25%) who had a total
      laryngectomy. Voice preservation was thus achieved in 75% of patients. No patient
      died because of the laryngeal cancer, and the observed 5-year survival rate was
      76%. CONCLUSIONS: These results indicate that in selected cases, endoscopic laser
      surgery may be used successfully for treating radiation failure of early
      laryngeal carcinomas.

PMID- 10897115
TI  - Granular cell tumor of the hypopharynx treated by endoscopic CO(2) laser
      excision: report of two cases.
AB  - BACKGROUND: Granular cell tumor (GCT), or Abrikossoff's tumor, is an unusual
      lesion probably arising from Schwann cells. It is frequently found in the head
      and neck region, where the tongue is the most commonly affected site. Involvement
      of the hypopharynx is exceedingly rare because, to the best of our knowledge,
      only four cases have been reported in the literature. METHODS: We describe
      hypopharyngeal GCT in two women aged 29 and 52 years, respectively. RESULTS: In
      the first patient, preoperative diagnostic examination, including endoscopy, CT,
      and MRI scan, was suggestive of a benign lesion arising from the posterior wall
      of the hypopharynx. In the second patient, a previous biopsy of the postcricoid
      area performed elsewhere suggested a diagnosis of well-differentiated squamous
      cell carcinoma, and CT scan staged the lesion as T1 N0. In both cases, treatment
      included surgical excision under microlaryngoscopy with CO(2) laser. The
      histopathologic study of the specimens, supported by immunohistochemical
      techniques, determined the lesions to be a GCT. The postoperative course was
      uneventful, and the patients were discharged 12 and 2 days after surgery,
      respectively. Both patients were asymptomatic without evidence of recurrence when
      last seen 2 years and 4 months after surgery, respectively. CONCLUSIONS: GCT
      should be included in the differential diagnosis of submucosal hypopharyngeal
      lesions. Endoscopy and radiologic imaging do not display any typical finding
      suggestive of the diagnosis, which can be based only on histologic findings.
      Resection of the tumor, when technically feasible, should be performed under
      microlaryngoscopy with the CO(2) laser, which makes it possible to work in a
      bloodless field with minimal thermal damage and reduction of scarring and
      postoperative edema.

PMID- 10897116
TI  - Congenital dyserythropoietic anemias: a still unsolved puzzle.

PMID- 10897117
TI  - Intracellular cytokine profile of cord blood T-, and NK- cells and monocytes.
AB  - BACKGROUND AND OBJECTIVES: Many functional peculiarities of cord blood (CB)
      lymphocytes and antigen presenting cells, including cytokine production, are
      associated with low intensity of innate and acquired (cellular and humoral)
      responses. These peculiarities may have implications both for immunologic
      maturation in post-natal life and for immune functions after CB transplantation
      [e.g. the lower incidence of graft-versus-host disease (GvHD) in comparison with
      after bone marrow transplantation (BMT)]. The aim of our study was to compare the
      intracellular production of cytokines involved both in phagocyte-dependent
      immunity/inflammation and in humoral immune responses in CB and adult peripheral
      blood (PB). DESIGN AND METHODS: Intracellular single cell analysis by flow
      cytometry was used to detect, following aspecific in vitro stimulation, the
      production of interferon (IFN)-gamma, Interleukin (IL)-2, IL-1alpha, IL-1beta, IL
      8, tumor necrosis factor (TNF)-alpha and -beta, IL-4, IL-5, IL-6, IL-10 and IL-13
      by T-cell subsets, NK-cells and monocytes obtained from 10 CB and 10 PB samples.
      The cytokine production was expressed as the percentage of positive cells.
      RESULTS: Significantly lower number of CD4+ T-cells producing IFN-g (p<0.001),
      TNF-alpha (p=0.012) and TNF-beta (p=0.03) and of CD8+ T-cells producing IFN-gamma
      (p<0.001), IL-2 (p=0.005) and TNF-alpha (p<0.001) were found in CB as compared to
      PB. In CB we have also found a lower number of NK cells and monocytes producing
      TNF-alpha (p<0.001 and p=0.001, respectively). In contrast, the number of IL
      1alpha+ monocytes was higher in CB than in PB (p=0.03). INTERPRETATION AND
      CONCLUSIONS: Our data confirm that the cytokines which normally sustain the
      phagocytic-dependent T helper/cytotoxic 1-type immune responses (IFN-gamma, IL-2
      and TNF-alpha) and the NK cell/monocyte-dependent aspecific responses (TNF-alpha)
      are reduced in CB. Since these cytokines are also involved in acute GvHD
      pathogenesis, these results are in keeping with the evidence of a low incidence
      of acute GvHD after CB transplantation.

PMID- 10897118
TI  - A comparative evaluation of gene transfer into blood cells using the same
      retroviral backbone for independent expression of the EGFP and deltaLNGFR marker
      genes.
AB  - BACKGROUND AND OBJECTIVES: Retroviral vectors are widely used to deliver foreign
      genes to hematopoietic stem cells (HSC). Improvement of marking protocols needs
      reporter genes to allow rapid detection and efficient selection of transduced
      cells. The great potential of EGFP and LNGFR as reporter systems prompted us to
      compare them simultaneously, using the same retroviral backbone and the same gene
      transfer procedures. DESIGN AND METHODS: The EGFP and LNGFR coding sequences were
      separately cloned into the MFG retroviral backbone. A cloning strategy assuring
      that both genes utilize the same ATG as the start codon was adopted. Marker gene
      expression, viral titers, transduction efficiency, and vector stability were
      evaluated in expanded amphotropic packaging clones and human hematopoietic cell
      lines by flow cytometry and PCR analysis. Vectors were also tested for their
      ability to transduce CD34+ peripheral blood cells. RESULTS: A significantly
      larger number of MFG- LNGFR packaging clones were obtained that produced high
      viral titers. A direct correlation between viral titer and marker gene expression
      in packaging clones was demonstrated for both constructs. Similar expression
      kinetics and absence of in vitro toxicity in transduced cells were also observed
      for both constructs. Successful infection of CD34+ cells was achieved even after
      a short time of exposure to recombinant viruses. INTERPRETATION AND CONCLUSIONS:
      Our results demonstrate that EGFP and LNGFR marker genes are equally useful for a
      rapid, specific and non-toxic detection of transduced cells. The MFG-EGFP
      construct appears useful to optimize gene transfer protocols in vitro. On the
      other hand, the MFG-LNGFR construct, for making possible a more efficient
      selection of high titer producer clones, as well as for safety and adaptability
      to the in vivo use, is more suitable for clinical applications.

PMID- 10897119
TI  - Fetal and embryonic hemoglobins in erythroblasts of chromosomally normal and
      abnormal fetuses at 10-40 weeks of gestation.
AB  - BACKGROUND AND OBJECTIVES: During fetal development a change in erythropoiesis
      from hepatic to medullary site occurs. In chromosomally abnormal fetuses this
      change is delayed. Hemoglobin production also undergoes developmental switches
      from embryonic to fetal hemoglobins in the first trimester of pregnancy. The aim
      of study was to determine the proportion of embryonic and fetal hemoglobins in
      fetal erythroblasts of chromosomally normal and abnormal fetuses at 10-40 weeks
      of gestation. DESIGN AND METHODS: Fetal blood was obtained from 93 chromosomally
      normal and 19 abnormal fetuses at 10-40 weeks of gestation. Fetal erythroblasts
      were isolated by triple density gradient centrifugation and magnetic cell sorting
      with CD71 antibody. Fluorescent antibodies were used to immuno-stain for zeta
      (zeta), epsilon (epsilon) and gamma (gamma) hemoglobin chains. RESULTS: The
      percentages of the positively stained cells were calculated. In chromosomally
      normal fetuses the percentage of erythroblasts expressing the zeta chain was 25%
      at 10 weeks but this decreased exponentially with gestation to less than 1% by 17
      weeks. Similarly, the percentage of cells expressing the epsilon chain decreased
      from 97% at 10 weeks to less than 1% by 25 weeks. In contrast, expression of the
      gamma chain increased from about 30% at 10 weeks to 90% by 16 weeks and decreased
      thereafter to 60% at 40 weeks. In the abnormal fetuses, the percentage of
      erythroblasts expressing the zeta chain and the epsilon chain decreased to less
      than 1% by 23 and 28 weeks respectively, while maximum expression of the gamma
      chain was at about 22 weeks. INTERPRETATION AND CONCLUSIONS: In the chromosomally
      abnormal group the pattern of change in the expression of the various hemoglobin
      chains during gestation was similar to that in the normal fetuses but was delayed
      by three to six weeks. These findings suggest that in fetuses with chromosomal
      abnormalities there is a developmental delay in the switch from embryonic to
      fetal hemoglobin chains.

PMID- 10897121
TI  - Relevance of presenting white blood cell count and kinetics of molecular
      remission in the prognosis of acute myeloid leukemia with CBFbeta/MYH11
      rearrangement.
AB  - BACKGROUND AND OBJECTIVES: The detection of CBFbeta/MYH11 transcripts by RT-PCR
      has became a valuable and widely used technique in the accurate cytogenetic and
      molecular classification of acute myeloid leukemia (AML), but the clinical value
      of RT-PCR for monitoring minimal residual disease (MRD) during follow-up remains
      unclear. DESIGN AND METHODS: We analyzed the factors predicting relapse and the
      value of MRD monitoring by RT-PCR in a series of 16 patients with CBFb/MYH11
      positive AML (15 M4Eo; 1 M4). Fifteen were newly diagnosed cases (CR1) and one
      was studied after first relapse (CR2). Eight patients had clinical relapse at 6
      to 19 months from the achievement of CR. RESULTS: Presenting WBC count had a
      significant prognostic influence on disease-free survival (p=0.001). All four
      patients with a WBC count >100x10(9)/L relapsed, while only four additional
      relapses occurred among the eleven patients who had an initial WBC count below
      100x10(9)/L. With regards to molecular monitoring, all relapses but one occurred
      in patients who showed persistent RT-PCR positivity during hematologic remission.
      By contrast, conversion to a repeatedly PCR-negative status was observed in the
      seven patients who remained in CR1 after a median follow-up of 48 months (range
      31-79 months), as well as in the transplanted patient who was monitored in CR2.
      In these patients a PCR-positivity could be detected up to 24 months after
      diagnosis (median time to conversion to PCR-negative: 8 months). INTERPRETATION
      AND CONCLUSIONS: In conclusion, marked hyperleukocytosis (>100x10(9)/L) confers
      poor prognosis to the patient with CBFbeta/MYH11-positive AML. In addition, slow
      kinetics of molecular remission was observed in this subset of AML, but the
      CBFb/MYH11 fusion transcript is no longer detectable in long-term survivors,
      indicating that molecular remission is an important therapeutic goal.

PMID- 10897120
TI  - Folate status in Italian blood donors: relation to gender and smoking.
AB  - BACKGROUND AND OBJECTIVES: Folate deficiency in the general population is
      associated with a risk of cardiovascular disease and various cancers. The aim of
      this study was to evaluate folate status in Italian blood donors and its
      relationship with gender and smoking habit. DESIGN AND METHODS: A prospective
      study of 201 first visit donors (99 males and 102 females) was undertaken to
      evaluate folate status by measuring serum folate (SF) and red blood cell folate
      (RCF) levels and relating those with gender and smoking habit (100 smokers and
      101 non-smokers). RESULTS: The rates of SF level less than 6.8 nmol/L and RCF
      less than 340 nmol/L were 9.9% and 25.3%, respectively in Italian blood donors.
      Mean RCF level was significantly lower (p<0.05) in females than in males and in
      smokers compared to non-smokers (p<0.001). The risk of reduced RCF levels in
      smokers was related to the number of cigarettes smoked per day, more than nine
      cigarettes increased the relative risk (RR) of low RCF level to 2.93 (95% C.I.:
      1.34-6.41). INTERPRETATION AND CONCLUSIONS: This study suggests that folate
      deficiency, evaluated by RCF and SF levels, is widespread in Italian blood
      donors. Moreover, RCF values seem related to gender in non-smokers and modified
      by smoking habit, according to the cigarettes number smoked per day.

PMID- 10897122
TI  - Combined use of reverse transcriptase polymerase chain reaction and flow
      cytometry to study minimal residual disease in Philadelphia positive acute
      lymphoblastic leukemia.
AB  - BACKGROUND AND OBJECTIVES: The Philadelphia chromosome in acute lymphoblastic
      leukemia (Ph+ ALL) is associated with a poor prognosis given the high frequency
      of chemoresistance and leukemia relapse. Minimal residual disease (MRD) detection
      before cytogenetic and hematologic relapse could be useful in early therapy. The
      most suitable methods for detecting MRD in Ph+ ALL are flow cytometry (FC) and
      reverse transcriptase polymerase chain reaction (RT-PCR). However, since both
      techniques carry the risk of false-negative results the combined use of these two
      techniques could overcome this problem. DESIGN AND METHODS: We report our
      experience using this approach in 47 bone marrow samples obtained from 10 Ph+ ALL
      patients. Twenty-seven marrow aspirates were taken from patients in clinical
      remission (CR). The samples were considered positive for MRD by FC when two
      conditions were met: 1) detection of an abnormal B-cell differentiation pattern
      and 2) presence of more than 1x10(-3) cells coexpressing CD22/CD34/CD45 or
      CD66/CD34/CD10. After FC analysis, RNA was purified using standard methods.
      RESULTS: FC was positive in 23/27 samples in CR (sensitivity 85%). RT-PCR was
      successfully performed in 23 samples in CR. RT-PCR was positive in 18/23 samples
      (sensitivity 78%). There were 5 samples with discordant results. FC was positive
      in 3 samples with a negative RT-PCR and FC was negative in 2 samples with a
      positive RT. All the 10 patients relapsed and only 1 is currently alive after an
      allogeneic stem cell transplantation (alloSCT). The median (range) time from MRD
      detection to relapse in patients treated with chemotherapy was 42 (39-71) days.
      INTERPRETATION AND CONCLUSIONS: These data suggest that RT-PCR may be negative
      despite the presence of neoplastic cells identified by their immunophenotypic
      traits. We conclude that immunologic and molecular techniques can be used in
      tandem for monitoring MRD in Ph+ ALL.

PMID- 10897123
TI  - Clinical significance of P-glycoprotein expression and function for response to
      induction chemotherapy, relapse rate and overall survival in acute leukemia.
AB  - BACKGROUND AND OBJECTIVES: A multidrug-resistance (MDR) phenotype mediated by P
      glycoprotein (P-gp) contributes to chemotherapy failure in acute leukemia.
      However, the exact prognostic significance of this resistance mechanism is still
      unclear, mostly due to methodologic problems in P-gp detection. We therefore
      investigated, whether P-gp expression levels or functional P-gp activity better
      predict response to induction chemotherapy, relapse rate and overall survival in
      acute leukemia. DESIGN AND METHODS: We examined cell samples of 121 adults with
      de novo acute myeloid leukemia (AML) and 102 children with newly diagnosed acute
      lymphoblastic leukemia (ALL) for P-gp expression and functional P-gp activity by
      flow cytometry. P-gp function was determined by the rhodamine 123 (rh123)-efflux
      test (AML n=121, ALL n=102) and P-gp expression levels using the P-gp specific
      monoclonal antibodies (moabs) MRK-16 (AML n=51, ALL n=31), 4.E3 (AML n=35, ALL
      n=32), or UIC-2 (AML n=68, ALL n=50). We correlated our findings with the
      immunophenotype, FAB morphology, cytogenetics and clinical data of the examined
      patients. RESULTS: P-gp expression levels as detected by MRK-16 and 4.E3 were
      very low and did not differ between AML and ALL as estimated using relative
      fluorescence intensity (RFI) values and D-values by Kolmogorow-Smirnov (KS)
      statistics. For moab UIC-2, P-gp expression levels were higher in AML than in
      ALL. Within AML, moab UIC-2 mainly reacted with myelomonocytic-differentiated
      leukemic cells of the FAB M4/5 subtypes. No correlation between P-gp expression
      levels as detected by MRK-16, 4.E3 or UIC-2 and the response to induction
      chemotherapy or relapse rate, both in AML and ALL, was observed. However, a
      prognostic impact of P-gp expression levels on overall survival in AML was seen
      for moab MRK-16. Moreover, within AML, P-gp function was higher in immature blast
      cells as defined by immunophenotype and FAB morphology and correlated with
      response to induction chemotherapy, relapse rate, overall survival as well as
      cytogenetic risk groups. In ALL, the overall functional P-gp activity was lower
      than in AML and did not correlate with immunophenotypical subgroups, response to
      induction chemotherapy, relapse rate or overall survival. INTERPRETATION AND
      CONCLUSIONS: Our data demonstrate a prognostic impact of P-gp in AML but not ALL
      and indicate that the functional rh123-efflux assay should be preferred for flow
      cytometric P-gp evaluation in acute leukemia compared with P-gp expression
      analysis by monoclonal antibodies.

PMID- 10897124
TI  - Lomustine and melphalan cannot be replaced by cyclophosphamide and etoposide
      without reducing efficacy in MOPPEBVCAD chemotherapy for advanced Hodgkin's
      disease.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the feasibility, toxicity and preliminary
      results of a potentially less toxic variant of the MOPPEBVCAD chemotherapy
      regimen for advanced Hodgkin's disease: MOPPEBVCyED, in which cyclophosphamide
      and etoposide replace lomustine and melphalan, respectively, with the remaining
      components being unaltered. DESIGN AND METHODS: The study was multicenter,
      prospective and randomized, and enrolled 67 patients with newly diagnosed stage
      IIB, III, IV Hodgkin's disease (62 were expected on the grounds of statistical
      considerations). Radiotherapy was restricted to sites of bulky involvement or to
      areas that responded incompletely to chemotherapy. Median follow-up was 48
      months. RESULTS: Comparing MOPPEBVCAD vs. MOPPEBVCyED, the results were as
      follows: complete remissions 35/35 vs. 30/32 (plus one partial remission and one
      disease progression); relapses 5 vs. 8; deaths 2 (one of myelodysplasia) vs. 2;
      delivered mean dose intensity (DI): lomustine 0.79+/-0.67 vs. cyclophosphamide
      0.82+/-0.32; melphalan 0.80+/-0.13 vs. etoposide 0.86+/-0.18; average DI of the 7
      drugs common to both regimens 0.73+/-0.10 vs. 0.83+/-0.11; all 9 drugs 0.75+/
      0.13 vs. 0.84+/-0.09 (p=0.002); projected 5-year failure-free survival 0.79 vs
      0.62; second cancers, two myelodysplasias vs. one carcinoma of the kidney.
      Toxicities were not statistically different except for heavier thrombocytopenia
      being recorded with MOPPEBVCAD. INTERPRETATION AND CONCLUSIONS: The higher
      cumulative and single drug DI recorded with MOPPEBVCyED may reflect better short
      term tolerability, but it does not lead to better disease control. Its late
      toxicity may be expected to be lower in the future but at present it does not
      seem to be a sufficient reason to substitute MOPPEBVCyED for MOPPEBVCAD.

PMID- 10897125
TI  - Efficacy of the VBM regimen in the treatment of elderly patients with Hodgkin's
      disease.
AB  - BACKGROUND AND OBJECTIVES: No specific chemotherapy regimens have yet been
      recommended for elderly Hodgkin's disease (HD) patients. We investigated the
      therapeutic efficacy and toxicity of the three-drug-combination VBM (vinblastine,
      bleomycin, and methotrexate) regimen in a group of 19 elderly HD patients. DESIGN
      AND METHODS: Vinblastine (6 mg/m(2) i.v.), bleomycin (10 mg/m(2) i.v.) and
      methotrexate (25 mg/m(2) i.v.) were administered on days 1 and 8. Chemotherapy
      was repeated every 28 days for a total of 6 cycles. Local radiotherapy was given
      only to patients who presented bulky disease at the time of diagnosis. Of the 19
      patients, 13 patients had stage II, 2 stage III, and 4 stage IV disease; the
      median age was 68 years (range 60 to 75). RESULTS: Of the 19 patients, 15 (79%)
      achieved complete response (CR) and 3 (16%) partial response, while the remaining
      patient showed no benefit from the treatment. With a median follow-up of 48
      months, the estimated 5-year relapse-free survival was 79%, and overall survival
      was 64%. Hematologic grade 3-4 toxicity was seen in only 1 (5%) patient; no
      severe non-hematologic side effects or deaths were associated with the
      administration of the VBM regimen. INTERPRETATION AND CONCLUSIONS: These
      preliminary data indicate that the VBM regimen provides a safe and effective
      therapeutic option for elderly patients with untreated HD.

PMID- 10897126
TI  - Patient management strategies and transplantation techniques in european stem
      cell transplantation centers offering breast cancer patients high-dose
      chemotherapy with peripheral blood stem cell support: a joint report from the
      EORTC and EBMT.
AB  - BACKGROUND AND OBJECTIVES: It is increasingly being realized that there are very
      considerable variations in individual hospitals' strategies for managing a
      particular group of patients, even if using similar therapeutic regimens. Such
      variations make it impossible to generalize estimations of treatment costs from
      one setting to others. The objective of this study is to examine the extent of
      variation in the current approaches in Europe to peripheral blood stem cell
      transplantation (PBSCT) in breast carcinoma. DESIGN AND METHODS: A questionnaire
      was developed and sent to the EBMT member institutions. The questionnaire
      comprised 85 questions covering the technical and clinical issues involved and
      the strategies followed for the management of the patients. This paper reports
      the results of the survey primarily by means of descriptive, univariate frequency
      distributions. The results of a more analytical approach, aiming at explaining
      patterns in the variations observed are also presented. RESULTS: A completed
      questionnaire was returned by 162 centers; 60% university hospitals, 14% cancer
      centers and the rest general hospitals. Considerable variations are observed
      between the centers with respect to all aspects of patient management and
      technical procedures investigated. In many respects, general hospitals follow
      different routines from university hospitals and dedicated cancer centers.
      INTERPRETATION AND CONCLUSIONS: Variability to the extent observed indicates an
      important scope for optimization of the procedures and a large potential for
      reduction of costs and perhaps for improvement of outcomes. Economic evaluations,
      for instance comparing PBSCT with autologous BMT as support for high dose
      chemotherapy, can not be generalized from one setting to another without careful
      examination of the procedures and strategies followed in each setting. European
      hospitals treating breast cancer patients with high dose chemotherapy supported
      by transplantation of peripheral blood stem cells use very different technical
      procedures for mobilization, harvest and re-implantation of stem cells. In
      addition, there are also wide variations in the way they manage the patients,
      e.g. with regard to the criteria for discharge from hospital after re
      implantation.

PMID- 10897127
TI  - Computed tomographic scan of the chest, latex agglutination test and plasma
      (1AE3)-beta-D-glucan assay in early diagnosis of invasive pulmonary
      aspergillosis: a prospective study of 215 patients.
AB  - BACKGROUND AND OBJECTIVES: Blood and radiologic tests are frequently used for
      diagnosis of invasive pulmonary aspergillosis, but it remains unknown which is
      more useful for its early diagnosis. Aim of the study was to compare usefulness
      of computed tomographic (CT) scan of chest, latex agglutination (LA) test and
      determination of plasma (1-->3)-beta-D-glucan (BDG) levels for early diagnosis of
      invasive pulmonary aspergillosis (IPA). DESIGN AND METHODS: We treated 215
      consecutive patients who underwent cytotoxic chemotherapy. From initiation of
      chemotherapy until death or discharge, blood samples were taken weekly and
      subjected to LA and BDG tests. We performed chest CT scans when patients had any
      signs of pulmonary infection or an antibiotic-resistant fever. RESULTS: Of the
      215 patients, 30 (14. 0%) were diagnosed as having IPA. In sixteen cases the
      diagnosis was definite and in 14 it was suspected. In patient-based analysis,
      sensitivities of LA and BDG were 44% and 63%, respectively. Sensitivity tended to
      be lower in patients with IPA localized to the lung than those with disseminated
      invasive aspergillosis. Specificities were 93% and 74%, respectively. Either a
      halo or an air-crescent was observed in 7 of the 16 patients with IPA, and all of
      the IPA patients showed some abnormal signs on chest CT scans. On average, CT
      scan signs preceded a positive LA test by 7.1 days and a positive BDG assay by
      11.5 days. In 6 of the 11 patients who became positive for either LA or BDG
      assay, CT scan signs preceded the positive results by more than seven days.
      INTERPRETATION AND CONCLUSIONS: Chest CT scan is more beneficial than the blood
      tests and X-ray for early diagnosis of IPA.

PMID- 10897130
TI  - Granulocytic sarcoma in a non-leukemic patient presenting with unusual cutaneous
      paraneoplastic syndrome.

PMID- 10897128
TI  - Congenital dyserythropoietic anemia type III.
AB  - BACKGROUND AND OBJECTIVES: Congenital dyserythropoietic anemia type III (CDA-III)
      is a group of very rare disorders characterized by similar bone marrow
      morphology. The clinical picture is characterized by hemolytic anemia and
      dramatic bone marrow changes dominated by active erythropoiesis with big
      multinucleated erythroblasts. The aim of this review is to describe the clinical
      manifestations, laboratory findings, and management CDA-III. EVIDENCE AND
      INFORMATION SOURCES: The present review critically examines relevant articles and
      abstracts published in journals covered by the Science Citation Index and
      Medline. The authors have performed several studies on CDA-III. STATE OF ART AND
      PERSPECTIVES: The clinical and laboratory manifestations of CDA-III indicate that
      the gene responsible for it, which has been mapped to chromosome 15q22, is
      expressed not only in erythroblasts during mitosis but also in B-cells, and in
      cells of the retina. Preliminary results indicate genetic and phenotypic
      similarities between a Swedish and an American family, both with an autosomally
      dominant inherited form of CDA-III. It is possible that the genetic lesion is
      identical in these families, but the different phenotypes and modes of
      inheritance reported among some other cases of CDA-III are probably the results
      of other genetic lesions. At present, the function of the gene responsible for
      the Swedish (V sterbotten) variant of CDA-III (CDAN3) is unknown and it is an
      important goal to characterize and clone this gene in order to study its
      function.

PMID- 10897129
TI  - Cutaneous promyelocytic sarcoma at sites of vascular access and marrow
      aspiration. A characteristic localization of chloromas in acute promyelocytic
      leukemia?
AB  - Extramedullary disease (EMD) is a rare clinical event in acute promyelocytic
      leukemia (APL). Although the skin is involved in half of the reported EMD cases,
      the occurrence of cutaneous promyelocytic sarcoma (PS) has been described very
      rarely. We report here three cases of PS which have the peculiarity of appearing
      at sites of punctures for arterial and venous blood and marrow samples (sternal
      manubrium, antecubital fossa, wrist over the radial artery pulse, catheter
      insertion scar). At presentation, all patients had hyperleukocytosis and a
      morphologic diagnosis of microgranular acute promyelocytic leukemia variant
      confirmed at the genetic level by demonstration of the specific chromosomal
      translocation t(15;17). A BCR3 type PML/RARa transcript was documented in the two
      patients for whom diagnostic RT-PCR was available. Patients had morphologic bone
      marrow remission at the time the PS appeared. A predilection for the development
      of cutaneous PS at sites of previous vascular damage has been noted, but the
      pathogenesis remains largely unknown. A potential role for all-trans retinoic
      acid has been advocated, although one of the three patients in our series had
      received no ATRA. A review of the literature revealed six similar cases and
      hyperleukocytosis at diagnosis was a consistent finding in all of them. A careful
      physical examination of these particular sites in the follow-up of patients at
      risk, as well as cutaneous biopsy and laboratory examination of suspected lesions
      are strongly recommended.

PMID- 10897132
TI  - Dihydrofolate reductase activity in the erythroblasts of patients with 5q-
      syndrome.

PMID- 10897131
TI  - Avid (67)Ga uptake in multiple myeloma relapsing after bone marrow transplant.

PMID- 10897133
TI  - Beneficial effect of low dose G-CSF and cyclosporin-A in a case of chronic
      neutropenia.

PMID- 10897134
TI  - Translocation (15;17)(q22;q21) not associated with acute promyelocytic leukemia
      and negative for PML/RARa rearrangement.

PMID- 10897136
TI  - Difficulties in the diagnosis of primary cardiac lymphomas.

PMID- 10897135
TI  - Lung toxicity following fludarabine, cytosine arabinoside and mitoxantrone (flan)
      treatment for acute leukemia.

PMID- 10897137
TI  - Gallium-67 uptake by cutaneous lesions in a patient with Burkitt-like non
      Hodgkin's lymphoma.

PMID- 10897138
TI  - Simultaneous occurrence of multiple myeloma and Hodgkin's disease. A case report.

PMID- 10897139
TI  - Demonstration of Epstein-Barr virus in a case of multiple myeloma after renal
      transplantation.

PMID- 10897140
TI  - A new case of Sezary cell leukemia: a morphological variant of prolymphocytic
      leukemia.

PMID- 10897141
TI  - Modifications of lymphocyte subsets in autoimmune thrombocytopenic purpura
      patients submitted to splenectomy.

PMID- 10897143
TI  - Effect of oral anticoagulant therapy on fibrinolysis parameters in chronic non
      rheumatic atrial fibrillation.

PMID- 10897144
TI  - Donor lymphocyte infusion for post-transplant relapse of Hodgkin's lymphoma.

PMID- 10897142
TI  - Abnormal bleeding in a patient with chronic lymphocytic leukemia and acute
      hepatitis due to a circulating heparin-like anticoagulant.

PMID- 10897145
TI  - Severe disseminated toxoplasmosis after unrelated bone marrow transplantation: a
      case report.

PMID- 10897146
TI  - Immunological short term reconstitution after tandem unselected peripheral blood
      progenitor cell transplantation for multiple myeloma.

PMID- 10897147
TI  - Characterization of neuronal migration disorders in neocortical structures: loss
      or preservation of inhibitory interneurons?
AB  - PURPOSE: Neuronal migration disorders (NMD) are often associated with therapy
      resistant epilepsy. In human cerebral cortex, this hyperexcitability has been
      correlated with a loss of inhibitory interneurons. We used a rat model of focal
      cortical NMD (microgyria) to determine whether the expression of epileptiform
      activity in this model coincides with a decrease in inhibitory interneurons.
      METHODS: In 2-to 4-month-old rats, the density of interneurons immunoreactive for
      gamma-aminobutyric acid (GABA), calbindin, and parvalbumin was determined in
      fronto-parietal cortex in nine 200-microm-wide sectors located up to 2.5 mm
      lateral and 2.0 mm medial from the lesion center in primary parietal cortex
      (Par1). Quantitative measurements in homotopic areas of age-matched sham-operated
      rats served as controls. RESULTS: The freeze lesion performed in newborn rat
      cortex resulted in adult rats with a microgyrus extending in a rostro-caudal
      direction from frontal to occipital cortex. The density of GABA-and parvalbumin
      positive neurons in fronto-parietal cortex was not significantly different
      between lesioned and control animals. Only the density of calbindin
      immunoreactive neurons located 1.0 mm lateral and 0.5 mm medial from the lesion
      was significantly (Student t test, p < 0.05) larger in freeze-lesioned rats
      (5,817 +/- 562 and 6,400 +/- 795 cells per mm3, respectively; n = 12) compared
      with measurements in homotopic regions in Par1 cortex of controls (4,507 +/- 281
      and 4, 061 +/- 319 cells per mm3, respectively; n = 5). CONCLUSIONS: The
      previously reported widespread functional changes in this model of cortical NMD
      are not related to a general loss of inhibitory interneurons. Other factors, such
      as a decrease in GABA receptor density, modifications in GABAA receptor subunit
      composition, or alterations in the excitatory network, e.g., an increase in the
      density of calbindin-immunoreactive pyramidal cells, more likely contribute to
      the global disinhibition and widespread expression of pathophysiological activity
      in this model of cortical NMD.

PMID- 10897148
TI  - Effect of ganaxolone on flurothyl seizures in developing rats.
AB  - PURPOSE: To determine the effects of a newly synthesized epalon, ganaxolone
      (GNX), on primarily generalized seizures in rats of various ages during
      development. Epalons are classified as neuroactive steroids that interact at
      unique site of the GABAA receptor-Cl- channel complex in the central nervous
      system. METHODS: Sprague-Dawley male rats were used at 9, 15, 30, and 60
      postnatal days (PN). GNX dissolved in 2-hydroxypropylbeta-cyclodextrine was
      administered intraperitoneally in different doses at various time points before
      flurothyl testing. The incidence and threshold of clonic and tonic-clonic
      flurothyl seizures were evaluated. Behavioral changes were also assessed.
      RESULTS: In all age groups, the effects of GNX were dose dependent and more
      prominent 10 min after its administration. In PN 60 and PN 30 rats, GNX had dose
      dependent anticonvulsant effects; tonic-clonic seizures were more sensitive to
      GNX treatment than clonic seizures. In PN 15 and PN 9 rats, GNX demonstrated dose
      and time-dependent anticonvulsant effects against both types of flurothyl-induced
      seizures. GNX was more effective in PN 15 rats than in other age groups, but at
      doses that altered motor behavior. CONCLUSIONS: GNX has anticonvulsant effects
      against flurothylinduced seizures in all age groups tested. Its effects are more
      prominent in the two younger age groups, especially in PN 15 rats, but are
      associated with motor side effects.

PMID- 10897150
TI  - Prevalence, classification, and severity of epilepsy in children in western
      Norway.
AB  - PURPOSE: To determine prevalence of active epilepsy in school children in a
      defined area and assess the usefulness of International League Against Epilepsy
      classification of seizures and epileptic syndromes, with special emphasis on
      frequency, additional handicaps, and therapeutic problems of severe cases.
      METHODS: The latest International League Against Epilepsy International
      Classification of Epileptic Seizures (ICES, 1981) and Epilepsies and Epileptic
      Syndromes (ICE, 1989) were used for determination of prevalence rates, seizure
      types, epilepsies and epileptic syndromes, and additional neurological deficits
      in all 6-to 12-year-old children with epilepsy in a Norwegian county. Children
      had neuropediatric and EEG examination, intelligence evaluation, and, when
      necessary, additional investigations. RESULTS: Prevalence of active epilepsy on
      January 1, 1995, was 5.1 per 1,000. Main seizure type and epilepsy syndrome could
      be classified in 98% and 90% of patients, respectively. Seizure types/epileptic
      syndromes were more often partial/localization related than generalized. Among
      generalized epilepsies, idiopathic forms were more frequent in girls, and
      cryptogenic and symptomatic forms more frequent in boys. Epileptogenic EEG
      activity was most often generalized or localized to one or two areas of the brain
      and was never found in 14% of patients. Symptomatic etiology was found in 46% of
      all children and in 81% of therapy-resistant cases, respectively. Over the years,
      11% of children had never used antiepileptic drugs (AED), 62% had tried one or
      two AEDs, and 26% had tried from three to 15 AEDs. Twenty-five percent of
      children were without present AED treatment. Complementary/alternative medicine
      had been tried by 12% of children. CONCLUSIONS: Although most epilepsies could be
      classified, the number of cases in non-specific categories was relatively high.
      Symptomatic etiology was frequent, especially in therapy-resistant cases.
      Multidisciplinary therapeutic and habilitation approaches are often needed in
      childhood epilepsy.

PMID- 10897149
TI  - Sleep and epilepsy: A key role for nitric oxide?
AB  - PURPOSE: It has been suggested that nitric oxide (NO) is involved in sleep
      mechanisms and in the pathophysiology of epilepsy. Data are, however,
      controversial because it is not clear whether NO facilitates sleep or waking, or
      whether it exerts pro-or antiepileptic influences. METHODS: The question was
      considered through NO voltammetric measurements and electroencephalographic
      recordings performed in GAERS rats (Genetic Absence Epilepsy Rat from
      Strasbourg): an experimental model of "petit-mal" human disease. Regulatory
      processes of sleep and epilepsy were studied after administration of a NO
      synthase inhibitor [l-arginine-p-nitroanilide (l-ANA) 100 mg/kg i.p.], a NO donor
      (SIN-1 100 ng/2 microl i.c.v.), and the antiepileptic drugs used in clinic
      [valproate (VPA 200 mg/kg i.p.) and ethosuximide (ESM 100 mg/kg i.p.)]. RESULTS:
      In GAERS rats, spontaneous circadian organizations of spike-wave discharges and
      paradoxical sleep (PS) occur in an opposite way; spontaneous NO concentrations
      are higher during seizures than during wakefulness, slow-wave sleep, and PS,
      respectively. l-ANA induces a disappearance of NO peak, an epileptic induction,
      and a loss of PS while SIN-1 induces opposite effects. Antiepileptic effects of
      VPA and ESM are associated with a PS increase and a significant release of NO.
      CONCLUSIONS: These results indicate that NO could be, in GAERS rats, a central
      piece in the reciprocal inhibitory mechanisms regulating the induction of PS and
      spike-wave discharges. NO could prevent absence epilepsy and act as an
      antiepileptic substance in facilitating PS. Antiepileptic efficiency of VPA and
      ESM may work through their ability to release NO. A track for a new treatment of
      petit-mal disease in children can be envisioned.

PMID- 10897151
TI  - Spatial distribution of neuronal complexity loss in neocortical lesional
      epilepsies.
AB  - PURPOSE: Nonlinear EEG analysis is valuable in characterizing the spatiotemporal
      dynamics of the epileptogenic process in mesial temporal lobe epilepsy. We
      examined the ability of the measure neuronal complexity loss (L*) to characterize
      the primary epileptogenic area of neocortical lesional epilepsies during the
      interictal state. METHODS: Spatial distribution of L* (L* map) was extracted from
      electrocorticograms (n = 52) recorded during presurgical assessment via subdural
      64-contact grid electrodes covering lesions in either frontal, parietal, or
      temporal neocortex in 15 patients. The exact location of recording contacts on
      the brain surface was identified by matching a postimplant lateral x-ray of the
      skull with a postoperatively obtained sagittal MRI scan. Reprojecting L* maps
      onto the subject's brain surface allowed us to compare the spatial distribution
      of L* with the resection range of the extended lesionectomy. RESULTS: In each of
      the six patients who became seizure-free, maximum values of L* were restricted to
      recording sites coinciding with the area of resection. In contrast, L* maps of
      most patients who had no benefit from the resection indicated a more widespread
      extent or the existence of additional, probably autonomous, foci. The mean of L*
      values obtained from recording sites outside the area of resection correctly
      distinguished 13 patients (86.7 %) with respect to seizure outcome. CONCLUSIONS:
      Relevant information obtained from long-lasting interictal electrocorticographic
      recordings can be compressed to a single L* map that contributes to a spatial
      characterization of the primary epileptogenic area. In neocortical lesional
      epilepsies, L* allows for identification and characterization of epileptogenic
      activity and thus provides an additional diagnostic tool for presurgical
      assessment.

PMID- 10897152
TI  - Reduction of benzodiazepine receptor binding is related to the seizure onset zone
      in extratemporal focal cortical dysplasia.
AB  - PURPOSE: Comparison of regional reduction of GABA receptor binding and seizure
      onset zone in patients with extratemporal epilepsy due to focal cortical
      dysplasia. METHODS: Two patients with frontal lobe epilepsy who remained seizure
      free after partial frontal lobe resection were investigated with magnetic
      resonance imaging, positron emission tomography (PET) with 18F-fluoro-deoxy
      glucose (FDG) and 11C-flumazenil, subdural EEG-video recordings, and
      postoperative benzodiazepine (BDZ)-receptor autoradiography. RESULTS: The area of
      reduced BDZ-receptor binding as documented by preoperative flumazenil-PET and
      postoperative BDZ-receptor autoradiography corresponded to the seizure onset zone
      and was smaller than the interictal hypometabolism documented by FDG-PET.
      CONCLUSION: Flumazenil-PET is a useful tool for localization of the epileptogenic
      zone in patients with extratemporal epilepsy caused by focal cortical dysplasia.
      Neuronal distribution of BDZ-receptor density confirms in vivo flumazenil-PET
      findings. The regional reduction of BDZ-receptor binding in focal cortical
      dysplasia seems to be confined to the seizure onset zone and not to the extent of
      dysplastic cortex.

PMID- 10897153
TI  - Proton magnetic resonance spectroscopic imaging studies in patients with newly
      diagnosed partial epilepsy.
AB  - PURPOSE: To assess whether the N-acetyl aspartate (NAA) to creatine ratio
      (NAA/Cr) is abnormally low at the onset of epilepsy and whether successful
      treatment of seizures with antiepileptic drugs is sufficient for normalization of
      NAA/Cr. PATIENTS AND METHODS: Proton magnetic resonance spectroscopic imaging (1H
      MRSI) was used to measure NAA/Cr in temporal lobes of eight patients with newly
      diagnosed epilepsy before or soon after starting medication. Six patients had
      follow-up 1H-MRSI examinations 7 months later. Clinical pattern of the seizures
      and the EEG findings suggested partial seizures in all and TLE in five patients.
      None of the patients had lesional epilepsy according to magnetic resonance
      imaging. RESULTS: Initial 1H-MRSI of the temporal lobes showed significantly low
      NAA/Cr values in five of eight patients. Five of six patients who had follow-up
      1H-MRSI were seizure-free after using medication; the remaining patient did not
      take medication and continued to experience occasional auras. Wilcoxon rank sign
      comparison of NAA/Cr on initial 1H-MRSI examination and follow-up 1H-MRSIs showed
      no significant difference (Z = 135, p = 0.893, 2-tailed) for five seizure-free
      patients. CONCLUSIONS: Neuronal dysfunction is present at an early stage of the
      epileptic process. NAA/Cr recovery in seizure-free patients controlled with
      antiepileptic drugs is less evident, compared with successful surgical treatment.
      Thus, absence of seizures is not necessarily coupled with NAA/Cr improvement and
      observed variable response warrants further investigation.

PMID- 10897154
TI  - Lateralization of temporal lobe epilepsy (TLE) and discrimination of TLE from
      extra-TLE using pattern analysis of magnetic resonance spectroscopic and
      volumetric data.
AB  - PURPOSE: To examine whether or not pattern analysis of magnetic resonance
      volumetric (MRVol) and proton magnetic resonance spectroscopic imaging (1H-MRSI)
      data would enable (a) the accurate lateralization of temporal lobe epilepsy (TLE)
      and (b) the discrimination of TLE from extratemporal epilepsy (E-TLE). METHODS:
      For lateralization analysis, we used data from 150 nonforeign tissue lesional TLE
      patients [88 left-sided (L-TLE), 46 right-sided (R-TLE), and 16 bilateral (Bi
      TLE)]. For the discrimination of TLE from E-TLE, we used data from 174 patients
      (145 with unilateral TLE, 14 with unilateral E-TLE, and 15 with widespread
      epileptogenic zones involving both the TL and extra-TL regions-multilobar
      epilepsy). A series of "leave-one-out" cross-validated linear discriminant
      analyses were performed using the MRVol and 1H-MRSI data sets to lateralize TLE
      and discriminate it from E-TLE. RESULTS: Lateralization: The leave-one-out linear
      discriminant analyses were able to correctly lateralize (with a posterior
      probability >0.50) 120 (90%) of the 134 L-TLE and R-TLE patients. Imposing higher
      posterior probability (>0.95) increased accuracy of lateralization to 98%, with
      only two discordant cases who underwent surgery on the side of
      electroencephalogram, and both had bad outcome. Discrimination: the leave-one-out
      linear discriminant analyses were able to correctly classify (with a posterior
      probability >0.50) 142 (89%) of the 159 TLE and E-TLE patients. Accuracy
      increased slightly as higher posterior probability cutoffs were imposed, with
      fewer patients being classified. CONCLUSIONS: Pattern analysis of 1H-MRSI and
      MRVol data can accurately lateralize TLE. Discriminating TLE from E-TLE was less
      accurate, probably due to the presence of temporal lobe damage in some patients
      with E-TLE reflecting dual pathology.

PMID- 10897155
TI  - Factors predictive of the outcome of frontal lobe epilepsy surgery.
AB  - PURPOSE: To identify factors that predict the outcome in seizure control after
      frontal lobe epilepsy surgery (FLES). FLES is the second most frequent type of
      epilepsy surgery, but the results are generally not as good as those after
      anterior temporal lobectomy. METHODS: Our cohort consisted of 68 consecutive
      patients whose first epilepsy surgery involving the frontal lobe occurred between
      1987 and 1994. Clinical history and results of imaging and
      electroencephalographic studies were reviewed in detail. Excellent outcome was
      defined as being seizure free or having only nondisabling seizures at last follow
      up. RESULTS: Forty of the 68 patients (58.8%) had an excellent outcome; none of
      the patients with a history of childhood febrile seizures had an excellent
      outcome, whereas outcome was excellent in 63% of those without that history (p
      </= 0.01). The other significant presurgical factor was the presence of a
      potentially epileptogenic lesion in the frontal lobe on neuroimaging (excellent
      outcome in 72% when present versus 41% when absent, p </= 0.001). The only
      significant postsurgical factor was early postoperative seizure control in the
      first year (excellent outcome in 96% with early control versus 25% without, p </=
      0.01). CONCLUSIONS: History of childhood febrile seizures is a poor prognostic
      factor in FLES patients. It may suggest that the structural basis of all or some
      of the patients' intractable seizures is mesial temporal sclerosis. On the other
      hand, neuroimaging detection of a potentially epileptogenic frontal lobe lesion
      and early postoperative seizure control are associated with subsequent excellent
      outcome.

PMID- 10897156
TI  - Rectal absorption of lamotrigine compressed tablets.
AB  - PURPOSE: Interruption of oral drug administration poses a significant clinical
      problem for antiepileptic drugs that have no parenteral formulation. If a drug is
      absorbed rectally, rectal administration can be a useful alternative when the
      oral route of administration is not possible. The purpose of this study was to
      compare the single-dose pharmacokinetics of lamotrigine (LTG) compressed tablets
      after rectal and oral administration in healthy volunteers. METHODS: A single LTG
      compressed tablet (100 mg) was administered orally and rectally to 12 volunteers
      in this single-dose, two-period, crossover study with a 2-week washout between
      doses. For rectal administration, tablets were crushed and suspended in 10 mL of
      water. Plasma samples were collected from 0 to 120 hr after each dose and
      analyzed for LTG by an HPLC method developed for this investigation. RESULTS: LTG
      plasma concentrations were lower after rectal administration versus oral
      administration. The average area under the curve was 28.90 +/- 9.5 microg/mL/hr
      after rectal administration and 51.71 +/- 19.2 microg/mL/hr after oral
      administration. The average maximum LTG concentration was 0.53 +/- 0.14 microg/mL
      after rectal administration and 1.45 +/- 0.35 microg/mL after oral
      administration. The relative bioavailability for LTG compressed tablets was 0.63
      +/- 0.33 for rectal administration. There were no drug-related rashes or serious
      side effects. CONCLUSIONS: LTG suspension prepared from LTG compressed tablets is
      absorbed rectally, although not to the same extent or rate as when given orally.

PMID- 10897157
TI  - Body dimensions of infants exposed to antiepileptic drugs in utero: observations
      spanning 25 years.
AB  - PURPOSE: To investigate the influence of maternal antiepileptic drug (AED)
      treatment on pregnancy duration, birth weight, body length, head circumference,
      and intrauterine growth in infants exposed in utero to antiepileptic drugs in
      Sweden between 1973-1997, with 963 singleton infants. METHODS: Data collected
      from (a) 1973-1981 (record linkage between a hospital discharge register and a
      medical birth register); (b) 1984-1995 (prospectively collected information in
      one defined catchment area with two delivery hospitals); and (c) 1995-1997
      (medical birth register data). Observed numbers of infants below a defined size
      for body measurements compared with expected numbers calculated from all births
      in Sweden after stratification for year of birth, maternal age, parity, and
      education or smoking habits in early pregnancy. Standard deviation scores
      estimated with same stratification procedures. RESULTS: Fraction of monotherapy
      exposures increased from approximately 40% to approximately 90% from 1973 to
      1997. Significantly increased numbers of infants with small body measurements
      found in exposed group. Negative influence on body dimensions decreased over
      time. More marked effects found in infants exposed to polytherapy. In
      monotherapy, only infants exposed to carbamazepine consistently showed reduction
      in body dimensions. Significant effect on gestational age in girls and on number
      of small for gestational age (<2 SD) in boys. CONCLUSIONS: Polytherapy with
      antiepileptic drugs and negative influence on body dimensions decreased. In
      monotherapy, only carbamazepine has a negative influence on body dimensions in
      this study.

PMID- 10897158
TI  - Lamotrigine-induced tic disorder: report of five pediatric cases.
AB  - PURPOSE: To describe the clinical spectrum of lamotrigine (LTG)-induced tics (an
      uncommon side effect) in children. METHODS: Retrospective analysis of patients
      from our hospital-based practice who developed tics while on LTG. Data obtained
      from medical records, interviews with parents, video-EEGs, and homemade
      videotapes. RESULTS: Three males and two females (range, 2.5-12 years; mean, 6.9
      years) developed a movement disorder within the first 10 months of therapy
      (maintenance doses, 4-17 mg/kg/day). Four patients exhibited simple motor tics;
      one patient experienced mostly vocal (i.e., gasping sounds) tics. Laryngoscopic
      evaluation of one 2.5-year-old with repetitive gasping sounds was normal. In
      three cases, tics resolved completely within 1 month of drug cessation; tics
      recurred in two of these patients after reintroduction of LTG. A fourth patient
      experienced gradual improvement after stopping LTG over 4 months; the fifth
      patient's simple motor tics improved spontaneously with a reduction in
      medication. None of the patients had clinical features of a neurodegenerative
      disorder, and none met diagnostic criteria for Tourette syndrome. Two patients,
      however, had a diagnosis of acquired epileptic aphasia syndrome, and one patient
      had nonprogressive expressive and receptive language dysfunction. A fourth
      patient had global static encephalopathy, and the fifth patient had only
      attentional problems. In all patients, tics were not associated with ictal EEG
      changes. CONCLUSIONS: LTG may infrequently induce simple motor tics, vocal tics,
      or both. Patients with severe language dysfunction may be particularly
      susceptible to this uncommon side effect. Further studies are necessary to
      clarify the population at risk.

PMID- 10897159
TI  - Effect of levetiracetam on epilepsy-related quality of life. N132 Study Group.
AB  - PURPOSE: To evaluate the short-term effect of levetiracetam (LEV; UCB L059) as
      add-on therapy on health-related quality of life in the treatment of refractory
      partial-onset seizures. METHODS: Patients were enrolled in protocol UCB N132 if
      they had >/=12 partial-onset seizures with or without secondary generalization
      during the 12-week baseline period with a minimum of two seizures every 4 weeks.
      Randomization was made to placebo, LEV 1,000 mg, or LEV 3,000 mg, with sample
      size based on seizure frequency reduction. The 31-item Quality of Life in
      Epilepsy (QOLIE-31) questionnaire was completed by 246 patients at the end of
      baseline and at 18-week follow-up, or earlier if withdrawn. RESULTS: Significant
      differences were found among the three treatment groups for Seizure Worry (p = 0.
      0003), Overall Quality of Life (p = 0.04), and Cognitive Functioning domains (p =
      0.01), as well as the Total Score (p = 0.009). Responders (>/=50% partial onset
      seizure reduction) had significant improvements in all areas, except Medication
      Effect, compared with nonresponders (all p > 0.006). Clinically noticeable
      improvement (>/=10% change from baseline to follow-up) was perceived by LEV 3,
      000 mg responders in all areas, except Emotional Well-Being, by LEV 1,000 mg
      responders in 5 of 9 areas, and by placebo responders in 2 of 9 areas.
      CONCLUSIONS: Addition of LEV to standard medication seems to have a positive
      impact on health-related quality of life, particularly among responders in this
      short-term study. These exploratory analyses require additional studies to
      evaluate long-term changes in a larger population.

PMID- 10897160
TI  - Conduct of trials in private clinical practice.
AB  - PURPOSE: Trials of antiepileptic medications are usually based in tertiary
      referral centers with teaching hospital resources. Epilepsy Research & Services
      (ERS) is part of a private outpatient neurological clinic that is involved in
      research as part of multicenter clinical trials, adhering to Good Clinical
      Research Practice. ERS is subject to external monitoring and auditing, but does
      so outside of the teaching hospital environment. METHODS: The clinic is operated
      by a neurologist supported by a research assistant, administrative and nursing
      staff and has no formal university attachment. Patients are recruited for trials
      from routine referrals for clinical care. The center has formal ties with the
      ethics committee of the local teaching hospital, but none of the team is formally
      attached to that hospital. RESULTS: The center conducted trials of zonisamide,
      oxcarbazepine, gabapentin, remacemide, tiagabine, vigabatrin, felbamate, and
      lamotrigine both as add-on trials in refractory seizure disorders and as
      monotherapy trials in de novo epilepsy. More than 200 patients have been
      recruited for trials at ERS (with some patients being involved in more than one
      trial). External review endorsed ERS as a superior environment for such research
      and as a model for other centers. CONCLUSIONS: Private practice is a viable
      alternative for the conduct of clincial trials and should be considered when
      establishing such protocols. Simplicity of administration and clinical practice,
      which more closely mirrors standard patient care, may enhance recruitment and
      management.

PMID- 10897161
TI  - Successful use of intravenous immunoglobulin as initial monotherapy in Landau
      Kleffner syndrome.
AB  - PURPOSE: There is a need for new and more effective therapies for Landau-Kleffner
      syndrome. In this article we present the first case in which a patient with
      Landau-Kleffner syndrome was given intravenous immunoglobulin (IVIG) as his first
      and only therapy and responded to it. METHODS: This previously healthy, left
      handed boy presented at 31 months of age with a 3-month history of auditory
      agnosia, behavioral abnormalities, and progressive, eventually complete loss of
      speech. Electroencephalography (EEG) showed frequent and, in sleep, continuous
      right central and temporal spike slow wave discharges. Metabolic workup, magnetic
      resonance imaging, and auditory evoked potentials were normal. Cerebrospinal
      fluid IgG index was high (18%). The patient was treated with IVIG, as his initial
      and only therapy, receiving 500 mg/kg/day over four consecutive days. RESULTS: On
      the third day of IVIG, the patient started using single words, and on the fourth,
      two-word sentences. Two weeks later his speech and behavior returned to normal.
      At the end of 4 days of IVIG therapy, EEG was within normal limits. Two months
      later, however, he had a severe relapse clinically and by EEG. He promptly
      responded to another course of IVIG. A subsequent cerebrospinal fluid IgG index
      showed normalization (6%). Three months later he had essentially normal speech
      and behavior. CONCLUSIONS: Repeated, immediate, and remarkable clinical and EEG
      responses of this patient suggest that IVIG was helpful as first-line therapy in
      the treatment of Landau-Kleffner syndrome. It also supports the hypothesis that
      immunological mechanisms contributed to his symptoms.

PMID- 10897162
TI  - Refractory idiopathic absence status epilepticus: A probable paradoxical effect
      of phenytoin and carbamazepine.
AB  - PURPOSE: To compare the frequency of seizures and status epilepticus and their
      response to first-line drugs in patients with idiopathic generalized epilepsies
      receiving carbamazepine or phenytoin to those receiving other drugs or no
      treatment. METHODS: We performed a retrospective chart review of all cases of
      idiopathic generalized epilepsies treated by the authors between 1985 and 1994.
      We compared seizure frequency and mean intravenous benzodiazepine dose required
      to control absence status epilepticus, intraindividually in subjects on
      carbamazepine or phenytoin before and after discontinuation of these compounds,
      and interindividually to subjects without treatment or receiving other drugs.
      RESULTS: Bouts of absence or tonic-clonic status epilepticus and seizures in
      subjects treated with phenytoin or carbamazepine at therapeutic concentrations
      were considerably more frequent and proved intractable to treatment with valproic
      acid or benzodiazepines, compared with a cohort of subjects also with idiopathic
      generalized epilepsies, but naive to, or receiving subtherapeutic or therapeutic
      doses of other agents. CONCLUSIONS: Our observations strongly suggest that
      therapeutic concentrations of phenytoin and carbamazepine exacerbate idiopathic
      generalized epilepsies. Subjects in whom absence is one of the seizure types seem
      at a particularly high risk for responding paradoxically. These findings
      underscore the value of accurate classification of seizures and particularly the
      syndromic approach to diagnosis and point to the potential for iatrogenic
      complications with indiscriminate use of antiseizure drugs.

PMID- 10897163
TI  - Should patients with psychogenic nonepileptic seizures be allowed to drive?
AB  - PURPOSE: To investigate the risk of driving accidents in patients with
      psychogenic nonepileptic seizures. METHODS: First, a survey was conducted in 82
      physician-members of the American Epilepsy Society to determine what they
      recommend in patients with psychogenic seizures in regard to driving privileges.
      Second, we studied a population of 20 patients with proven psychogenic
      nonepileptic seizures diagnosed by prolonged EEG-video monitoring. We obtained
      the patients' driving records from the Wisconsin Department of Transportation. We
      used 1991 Wisconsin crash data as the reference year. We compared the expected
      number of motor vehicle crashes with the observed number of crashes. chi2 with
      Yates' correction for continuity was used to test for statistical significance.
      RESULTS: Of the 82 physicians questioned, 37 (45%) responded. Among respondents,
      the distribution was as follows: 49% applied the same restrictions as for
      patients with epilepsy; 32% did not place patients under any restrictions; and
      19% decided on a case-by-case basis. The total number of reported crashes in the
      sample was eight, with no fatal crashes. This was not statistically significant
      (corrected chi2, 0.53) compared with the expected number of motor vehicle crashes
      for the sample. CONCLUSIONS: This small series does not support the use of
      driving restrictions for patients with psychogenic nonepileptic seizures.

PMID- 10897164
TI  - An unusual complication of intracranial electrodes.
AB  - This report describes two patients who developed persistent neurologic deficits
      during intracranial EEG recording without clear evidence of intracranial edema or
      infarction. Both patients had previously received high-dose brain radiation
      therapy and chemotherapy. Because of this experience, we strongly caution the use
      of intracranial electrodes in patients with similar profiles.

PMID- 10897165
TI  - Tonsillar pain mimicking glossopharyngeal neuralgia as a complication of vagus
      nerve stimulation: case report.
AB  - An adolescent girl presented with severe, lancinating tonsillar pain exacerbated
      by swallowing 6 weeks after initiation of left vagus nerve stimulation for
      intractable epilepsy. Her symptoms mimicked those seen in glossopharyngeal
      neuralgia and were relieved by temporary cessation of stimulation. Gradual
      reinstitution of therapy with alteration in stimulus parameters resulted in
      improved seizure control as well as cessation of pain symptoms. Direct
      stimulation of the vagus nerve may result in vagoglossopharyngeal neuralgia,
      which, in this case, was amenable to stimulus modification.

PMID- 10897167
TI  - Valproic acid-induced hyperammonemic encephalopathy with triphasic waves.
AB  - PURPOSE: To examine a patient with valproic acid (VPA)-induced hyperammonemic
      encephalopathy accompanied by triphasic waves. METHODS: A 61-year-old male
      patient with epilepsy experienced disturbance of consciousness after VPA dose was
      increased because of poor seizure control. The electroencephalogram (EEG) taken
      on admission revealed triphasic waves and high-amplitude delta-activity with
      frontal predominance. Although serum hepatic enzymes, such as AST and ALT, were
      normal, serum ammonium level was high at 96 microg/dl (normal range, 3-47
      microg/dl). Serum amino acid analysis showed multiple minor abnormalities.
      Administration of VPA was discontinued immediately after admission, while other
      anticonvulsants were continued. RESULTS: The patient's condition was improved on
      the fourth day of admission. An EEG, serum ammonium level, and amino acid profile
      were normal on the eighth day. Based on VPA administration, serum ammonium
      levels, and results of amino acid analysis, this patient had VPA-induced
      hyperammonemic encephalopathy. CONCLUSIONS: Our case indicates that caution is
      required if triphasic waves appear in VPA-induced hyperammonemic encephalopathy.

PMID- 10897166
TI  - Abnormal Wada and neuropsychological testing results due to topiramate therapy.
AB  - A 46-year-old man experienced intractable seizures since childhood. Due to lack
      of response to antiepilepsy drugs (AEDs), he underwent a surgical evaluation that
      was consistent with seizure onset in the left medial temporal lobe. While on
      topiramate and carbamazepine, his preoperative neuropsychological scores and
      sodium amytal (Wada) scores were low and may have excluded him from surgery.
      Repeat testing on lamotrigine and carbamazepine showed improvement in his scores,
      allowing him to undergo surgery. Physicians must therefore be cautious in
      evaluating such test scores while a patient is on topiramate.

PMID- 10897168
TI  - The epilepsy of Emperor Michael IV, Paphlagon (1034-1041 A.D.): accounts of
      Byzantine historians and physicians.
AB  - PURPOSE: Presentation of epilepsy suffered by Byzantine Emperor Michael IV,
      Paphlagon (who reigned from 1034 to 1041 A.D.) and the attitude of his
      contemporary society to his disorder. METHODS: Research into the accounts of
      Byzantine historians and chroniclers referring to the case of the emperor and
      Byzantine medical texts revealing the opinion of official medicine about the
      disorder. RESULTS: Byzantine historians and chroniclers provide detailed clinical
      descriptions of the seizures of Emperor Michael IV. Nearly all, expressing
      popular opinion, considered his disease to be demonic possession that constituted
      a form of divine punishment for the emperor's adultery and act of murder; his
      royal entourage continually attempted euphemistically to present this condition
      as a psychic disease. On the contrary, research into Byzantine medical texts
      reveals that the physicians, already from the 4th century, following Hippocratic
      tradition, believed that epilepsy was primarily a brain-related disorder and
      based their treatment on this etiological principle. CONCLUSIONS: From the study
      of the Byzantine histories and chronicles, it can be deduced that Emperor Michael
      IV, Paphlagon, suffered from generalized tonic-clonic epileptic seizures. Despite
      the concept then held by well-educated Byzantine doctors, who considered epilepsy
      a brain disorder, information indicates the deep prejudices of his social
      environment.

PMID- 10897169
TI  - Re: Mazarati et al. "...clinically available [antiepileptic drug] with a moderate
      affinity for the glycine site of the N-methyl-D-aspartate (NMDA) receptor".

PMID- 10897171
TI  - Re: Begemann et al. article describing the first case of nonconvulsive status
      epilepticus (NCSE) successfully treated with propofol.

PMID- 10897170
TI  - Emphasis in medicine on statistically sound and unbiased (blinded) research.

PMID- 10897172
TI  - Re: Sadler's article regarding lamotrigine-associated insomnia in an adult
      tertiary care epilepsy out-patient clinic.

PMID- 10897173
TI  - The public health challenges of the HIV epidemic.

PMID- 10897174
TI  - Children and older persons: AIDS' unseen victims.

PMID- 10897175
TI  - A change in approach to prenatal HIV screening.

PMID- 10897176
TI  - Ignore AIDS and it will bury the rest of you.

PMID- 10897177
TI  - HIV prevention research: accomplishments and challenges for the third decade of
      AIDS.
AB  - The past 2 decades have taught us that HIV prevention can work. We now have
      evidence from places as diverse as Senegal, Thailand, Uganda, and Australia that
      concerted HIV prevention efforts at the national level have resulted in the
      maintenance of low seroprevalence rates where they otherwise would have been
      expected to rise. We are beginning to observe declining rates of HIV prevalence
      and incidence in places and populations with historically high rates--for
      example, injection drug users in New York City. This trend points to the long
      term impact of prevention efforts in those communities. The best of these efforts
      have been based on sound scientific research. As we move into the third decade of
      the AIDS epidemic, it is important to restate principles, acknowledge advances,
      and identify challenges and future directions in HIV prevention research.

PMID- 10897178
TI  - HIV: challenging the health care delivery system.
AB  - HIV offers a lens through which the underlying problems of the US health care
      system can be examined. New treatments offer the potential of prolonged quality
      of life for people living with HIV if they have adequate access to health care.
      However, increasing numbers of new cases of HIV occur among individuals with poor
      access to health care. Restrictions on eligibility for Medicaid (and state-by
      state variability) contribute to uneven access to the most important safety net
      source of HIV care financing, while relatively modest discretionary programs
      attempt to fill in the gap with an ever-increasing caseload. Many poor people
      with HIV are going without care, even though aggregate public spending on HIV
      related care will total $7.7 billion in fiscal year 2000, an amount sufficient to
      cover the care costs of one half of those living with HIV. But inefficiencies and
      inequities in the system (both structural and geographic) require assessment of
      the steps that can be taken to create a more rational model of care financing for
      people living with HIV that could become a model for all chronic diseases.

PMID- 10897179
TI  - Tracking the HIV epidemic: current issues, future challenges.
AB  - The emergence of a new infectious disease, AIDS, in the early 1980s resulted in
      the development of a national AIDS surveillance system. AIDS surveillance data
      provided an understanding of transmission risks and characterized communities
      affected by the epidemic. Later, these data provided the basis for allocating
      resources for prevention and treatment programs. New treatments have dramatically
      improved survival. Resulting declines in AIDS incidence and deaths offer hope
      that HIV disease can be successfully managed. However, to prevent and control
      HIV/AIDS in the coming decades, the public health community must address new
      challenges. These include the defining of the role of treatment in reducing
      infectiousness; the potential for an epidemic of treatment-resistant HIV; side
      effects of treatment; complacency that leads to relapses to high-risk behaviors;
      and inadequate surveillance and research capacity at state and local levels to
      guide the development of health interventions. Meeting these challenges will
      require reinvesting in the public health capacity of state and local health
      departments, restructuring HIV/AIDS surveillance programs to collect the data
      needed to guide the response to the epidemic, and providing timely answers to
      emerging epidemiologic questions.

PMID- 10897180
TI  - Culture, sexuality, and women's agency in the prevention of HIV/AIDS in southern
      Africa.
AB  - Using an ethnographic approach, the authors explored the awareness among women in
      southern Africa of the HIV epidemic and the methods they might use to protect
      themselves from the virus. The research, conducted from 1992 through 1999,
      focused specifically on heterosexual transmission in 5 sites that were selected
      to reflect urban and rural experiences, various populations, and economic and
      political opportunities for women at different historical moments over the course
      of the HIV epidemic. The authors found that the female condom and other woman
      controlled methods are regarded as culturally appropriate among many men and
      women in southern Africa and are crucial to the future of HIV/AIDS prevention.
      The data reported in this article demonstrate that cultural acceptability for
      such methods among women varies along different axes, both over time and among
      different populations. For this reason, local circumstances need to be taken into
      account. Given that women have been clearly asking for protective methods they
      can use, however, political and economic concerns, combined with historically
      powerful patterns of gender discrimination and neglect of women's sexuality, must
      be viewed as the main obstacles to the development and distribution of methods
      women can control.

PMID- 10897181
TI  - The social geography of AIDS and hepatitis risk: qualitative approaches for
      assessing local differences in sterile-syringe access among injection drug users.
AB  - While significant gains have been achieved in understanding and reducing AIDS and
      hepatitis risks among injection drug users (IDUs), it is necessary to move beyond
      individual-level characteristics to gain a fuller understanding of the impact of
      social context on risk. In this study, 6 qualitative methods were used in
      combination with more traditional epidemiologic survey approaches and laboratory
      bioassay procedures to examine neighborhood differences in access to sterile
      syringes among IDUs in 3 northeastern cities. These methods consisted of (1)
      neighborhood-based IDU focus groups to construct social maps of local equipment
      acquisition and drug use sites; (2) ethnographic descriptions of target
      neighborhoods; (3) IDU diary keeping on drug use and injection equipment
      acquisition; (4) ethnographic day visits with IDUs in natural settings; (5)
      interviews with IDUs about syringe acquisition and collection of syringes for
      laboratory analysis; and (6) focused field observation and processual
      interviewing during drug injection. Preliminary findings from each of these
      methods are reported to illustrate the methods' value in elucidating the impact
      of local and regional social factors on sterile syringe access.

PMID- 10897182
TI  - Project CREST: a new model for mental health intervention after a community
      disaster.

PMID- 10897183
TI  - Perceived unmet need for oral treatment among a national population of HIV
      positive medical patients: social and clinical correlates.
AB  - OBJECTIVES: This study examines social, behavioral, and clinical correlates of
      perceived unmet need for oral health care for people with HIV infection. METHODS:
      Baseline in-person interviews with 2864 individuals were conducted with the HIV
      Cost and Services Utilization Study cohort, a nationally representative
      probability sample of HIV-infected persons in medical care. Bivariate and
      logistic regression analyses were conducted, with unmet need in the last 6 months
      as the dependent variable and demographic, social, behavioral, and disease
      characteristics as independent variables. RESULTS: We estimate that 19.3% of HIV
      infected medical patients (n = 44,550) had a perceived unmet need for dental care
      in the last 6 months. The odds of having unmet dental needs were highest for
      those on Medicaid in states without dental benefits (odds ratio [OR] = 2.21), for
      others with no dental insurance (OR = 2.26), for those with incomes under $5000
      (OR = 2.20), and for those with less than a high school education (OR = 1.83).
      Low CD4 count was not significant. CONCLUSIONS: Perceived unmet need was related
      more to social and economic factors than to stage of infection. An expansion of
      dental benefits for those on Medicaid might reduce unmet need for dental care.

PMID- 10897184
TI  - Economic deprivation and AIDS incidence in Massachusetts.
AB  - OBJECTIVES: This study quantified AIDS incidence in Massachusetts in relation to
      economic deprivation. METHODS: Using 1990 census block-group data, 1990 census
      population counts, and AIDS surveillance registry data for the years 1988 through
      1994, we generated yearly and cumulative AIDS incidence data for the state of
      Massachusetts stratified by sex and by neighborhood measures of economic position
      for the total, Black, Hispanic, and White populations. RESULTS: Incidence of AIDS
      increased with economic deprivation, with the magnitude of these trends varying
      by both race/ethnicity and sex. The cumulative incidence of AIDS in the total
      population was nearly 7 times higher among persons in block-groups where 40% or
      more of the population was below the poverty line (362 per 100,000) than among
      persons in block-groups where less than 2% of the population was below poverty
      (53 per 100,000). CONCLUSIONS: Observing patterns of disease burden in relation
      to neighborhood levels of economic well-being elucidates further the role of
      poverty as a population-level determinant of disease burden. Public health
      agencies and researchers can use readily available census data to describe
      neighborhood-level socioeconomic conditions. Such knowledge expands options for
      disease prevention and increases the visibility of economic inequality as an
      underlying cause of AIDS.

PMID- 10897185
TI  - HIV-infected parents and their children in the United States.
AB  - OBJECTIVES: This study sought to determine the number, characteristics, and
      living situations of children of HIV-infected adults. METHODS: Interviews were
      conducted in 1996 and early 1997 with a nationally representative probability
      sample of 2864 adults receiving health care for HIV within the contiguous United
      States. RESULTS: Twenty-eight percent of infected adults in care had children.
      Women were more likely than men to have children (60% vs 18%) and to live with
      them (76% vs 34%). Twenty-one percent of parents had been hospitalized during the
      previous 6 months, and 10% had probably been drug dependent in the previous year.
      Parents continued to have children after being diagnosed with HIV: 12% of all
      women conceived and bore their youngest child after diagnosis, and another 10%
      conceived before but gave birth after diagnosis. CONCLUSIONS: Clinical and
      support services for people affected by the HIV epidemic should have a family
      focus.

PMID- 10897186
TI  - Bridging the gap between the science and service of HIV prevention: transferring
      effective research-based HIV prevention interventions to community AIDS service
      providers.
AB  - OBJECTIVES: AIDS service organizations (ASOs) rarely have access to the
      information needed to implement research-based HIV prevention interventions for
      their clients. We compared the effectiveness of 3 dissemination strategies for
      transferring HIV prevention models from the research arena to community providers
      of HIV prevention services. METHODS: Interviews were conducted with the directors
      of 74 ASOs to assess current HIV prevention services. ASOs were randomized to
      programs that provided (1) technical assistance manuals describing how to
      implement research-based HIV prevention interventions, (2) manuals plus a staff
      training workshop on how to conduct the implementation, or (3) manuals, the
      training workshop, and follow-up telephone consultation calls. Follow-up
      interviews determined whether the intervention model had been adopted. RESULTS:
      The dissemination package that provided ASOs with implementation manuals, staff
      training workshops, and follow-up consultation resulted in more frequent adoption
      and use of the research-based HIV prevention intervention for gay men, women, and
      other client populations. CONCLUSIONS: Strategies are needed to quickly transfer
      research-based HIV prevention methods to community providers of HIV prevention
      services. Active collaboration between researchers and service agencies results
      in more successful program adoption than distribution of implementation packages
      alone.

PMID- 10897187
TI  - HIV testing among the general US population and persons at increased risk:
      information from national surveys, 1987-1996.
AB  - OBJECTIVES: We used data from national surveys to measure the rate of HIV testing
      in the general US population and among persons at increased behavioral risk and
      summarized what has been learned about HIV testing from these surveys. METHODS:
      Three nationally representative surveys were used: the National Health Interview
      Survey for 1987 through 1995, the 1995 National Survey of Family Growth, and the
      1996 National Household Survey on Drug Abuse. These surveys asked about HIV
      testing experience and behavioral risks for HIV. Rates of testing were computed
      for all persons, including those at increased risk for HIV. RESULTS: From 1987 to
      1995, the percentage of adults ever tested increased from 16% to 40%. The 3
      surveys were consistent with one another, and all showed much higher rates of
      testing for persons at increased risk for HIV. CONCLUSIONS: Surveys have provided
      information on HIV testing that is not available elsewhere, including rates of
      testing from private sources and public programs. Efforts to measure HIV testing
      and its correlates should continue and should be improved to provide information
      essential for effective programs.

PMID- 10897188
TI  - A participant observation study using actors at 30 publicly funded HIV counseling
      and testing sites in Pennsylvania.
AB  - OBJECTIVES: This study was designed to augment an evaluation of Pennsylvania
      publicly funded HIV counseling and testing sites, particularly of the staff
      client interaction. METHODS: Actors were trained as research assistants and sent
      to 30 randomly chosen sites to be tested and counseled for HIV disease.
      Instruments based on Centers for Disease Control and Prevention (CDC) guidelines
      were designed and used to evaluate them. RESULTS: Data were generated that
      identified the range of compliance with CDC guidelines and state policy. Among
      the findings were that 10 of 30 sites required signed consents despite a state
      policy allowing anonymous testing. Only 17% of providers developed a written risk
      reduction plan, even though 69% of all sites surveyed by mail asserted that such
      plans were developed. Only 2 of 5 HIV-positive actors were offered partner
      notification services, even though 100% of sites visited by an interviewer
      claimed to offer such services. CONCLUSIONS: The findings suggest that although
      evaluation methods such as mail surveys and site visits are useful for evaluating
      the existence of appropriate policies and protocols and gathering baseline data,
      they might not be sufficient for assessing actual staff-client interaction.

PMID- 10897190
TI  - Behavioral risk reduction in a declining HIV epidemic: injection drug users in
      New York City, 1990-1997.
AB  - OBJECTIVES: This study assessed trends in HIV risk behaviors among injection drug
      users in New York City from 1990 to 1997. METHODS: Injection drug users were
      recruited continuously from a large drug detoxification treatment program (N =
      2588) and a research storefront located in a high-drug-use area (N = 2701).
      Informed consent was obtained, and a trained interviewer administered a
      structured interview covering sociodemographics, drug use history, HIV risk
      behavior, and participation in syringe exchange. RESULTS: Trends were assessed
      for 5 risk behaviors in the 6-month period before the interview. The 3 injection
      risk behaviors declined significantly over time at each site (all P < .01). When
      data were pooled across sites, all 5 risk behaviors declined significantly over
      time (all P < .01). Participation in syringe exchange programs and in HIV
      counseling and testing increased greatly from 1990 to 1997. CONCLUSIONS: The
      continuing risk reduction among injection drug users indicates a "declining
      phase" in the large HIV epidemic in New York City. HIV prevention programs appear
      to be making an important contribution to the declining phase.

PMID- 10897189
TI  - HIV transmission and the cost-effectiveness of methadone maintenance.
AB  - OBJECTIVES: This study determined the cost-effectiveness of expanding methadone
      maintenance treatment for heroin addiction, particularly its effect on the HIV
      epidemic. METHODS: We developed a dynamic epidemic model to study the effects of
      increased methadone maintenance capacity on health care costs and survival,
      measured as quality-adjusted life-years (QALYs). We considered communities with
      HIV prevalence among injection drug users of 5% and 40%. RESULTS: Additional
      methadone maintenance capacity costs $8200 per QALY gained in the high-prevalence
      community and $10,900 per QALY gained in the low-prevalence community. More than
      half of the benefits are gained by individuals who do not inject drugs. Even if
      the benefits realized by treated and untreated injection drug users are ignored,
      methadone maintenance expansion costs between $14,100 and $15,200 per QALY
      gained. Additional capacity remains cost-effective even if it is twice as
      expensive and half as effective as current methadone maintenance slots.
      CONCLUSIONS: Expansion of methadone maintenance is cost-effective on the basis of
      commonly accepted criteria for medical interventions. Barriers to methadone
      maintenance deny injection drug users access to a cost-effective intervention
      that generates significant health benefits for the general population.

PMID- 10897192
TI  - Predicting smoking cessation and major depression in nicotine-dependent smokers.
AB  - OBJECTIVES: This study examined the relationship of nicotine dependence with
      smoking cessation and major depression, using the Fagerstrom Test for Nicotine
      Dependence (FTND) and the Diagnostic and Statistical Manual of Mental Disorders,
      Revised Third Edition (DSM-III-R). METHODS: In an epidemiologic study of young
      adults that used the FTND and the National Institute of Mental Health Diagnostic
      Interview Schedule, 238 daily smokers were assessed with respect to nicotine
      dependence. Cessation (abstinence for 1 year or more) was assessed 2 years later.
      RESULTS: FTND-defined nicotine dependence predicted cessation, with non-dependent
      smokers 4 times more likely to quit. DSM-III-R-defined nicotine dependence also
      predicted cessation, but much more weakly. Number of cigarettes per day was the
      best predictor of cessation. FTND-defined dependence was unrelated to major
      depression, whereas DSM-III-R-defined dependence signaled a 3-fold risk for major
      depression. The association of DSM-III-R-defined nicotine dependence with major
      depression might be driven by the behavioral rather than the physiologic symptoms
      of dependence. CONCLUSIONS: The more a measure of dependence is based exclusively
      on level of daily smoking, the greater is its ability to predict cessation. The
      number of DSM-III-R behavioral symptoms might be an indicator of severity of
      dependence or of personality traits, which in turn might be associated with major
      depression.

PMID- 10897191
TI  - Frequent use of lubricants for anal sex among men who have sex with men: the HIV
      prevention potential of a microbicidal gel.
AB  - OBJECTIVES: This study assessed frequency of rectal lubricant use, opinions about
      rectal microbicidal gels, and willingness to participate in acceptability trials
      of rectal microbicides among Latino men who have sex with men (MSM). METHODS:
      Latino MSM (N = 307) living in New York City were surveyed from October 1995
      through November 1996. Eleven Latino MSM participated in a focus group. RESULTS:
      Among those having anal sex during the prior year, 93% used lubricants (59%
      always and 74% in at least 80% of sexual encounters) regardless of condom use. Of
      the 29 men who practiced anal sed but did not use condoms, 90% used lubricants
      with similar frequency. Of those using lubricants, 94% used at least 1 teaspoon
      per occasion. A transparent product, free of smell and taste, was favored. Of the
      MSM in the sample, 92% said that they would use a lubricant with an anti-HIV
      microbicidal agent, and 87% expressed interest in participating in an
      acceptability trial. Product and dispenser preferences also were discussed.
      CONCLUSIONS: A rectal lubricant with microbicidal properties appears acceptable
      and desirable to Latino men who have anal sex with other men.

PMID- 10897193
TI  - Racial and ethnic differences in the use of cardiovascular procedures: findings
      from the California Cooperative Cardiovascular Project.
AB  - OBJECTIVES: This study used data from the California Cooperative Cardiovascular
      Project to examine the use of invasive and noninvasive cardiovascular procedures
      among Whites, African Americans, and Hispanics. METHODS: The use of
      catheterization, percutaneous transluminal coronary angioplasty (PTCA), coronary
      artery bypass graft (CABG) surgery, and several noninvasive tests among all
      patients 65 years or older with a confirmed acute myocardial infarction in
      nonfederal hospitals from 1994 to 1995 was studied. RESULTS: African Americans (n
      = 527) were less likely than Whites (n = 9489) to have received catheterization
      (adjusted odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.50, 0.76),
      PTCA (OR = 0.64, 95% CI = 0.49, 0.85), or CABG surgery (OR = 0.42, 95% CI = 0.27,
      0.64); somewhat more likely to have received a stress test or an echocardiogram;
      and equally likely to have received a multiple-gated acquisition scan. Hispanics
      (n = 689) also were less likely than Whites to have received catheterization (OR
      = 0.82, 95% CI = 0.68, 0.98) or PTCA (OR = 0.58, 95% CI = 0.45, 0.75).
      CONCLUSIONS: African Americans were less likely than Whites to undergo costly
      invasive cardiovascular procedures. In addition, Hispanics were less likely than
      Whites to have received catheterization and PTCA.

PMID- 10897194
TI  - Preaching to the choir: preference for female-controlled methods of HIV and
      sexually transmitted disease prevention.
AB  - OBJECTIVES: This study assessed interest in female-controlled methods of HIV and
      sexually transmitted disease (STD) prevention. METHODS: Surveys were conducted
      with 168 African American women, aged 18 to 32 years, who had had unprotected sex
      and at least 3 sexual partners in the last 2 years. RESULTS: Of 44 potential
      features, "female control" (where women control the method by either wearing or
      applying it) ranked 22nd in average importance. Women who rated female control as
      highly important had fewer sex partners and fewer STDs and were more likely to
      use existing prevention methods frequently. CONCLUSIONS: Female control may be of
      less interest to women most at risk for HIV and other STDs. This underscores the
      need to take the priorities and preferences of women into consideration when
      developing new prevention methods.

PMID- 10897195
TI  - Delays in seeking HIV care due to competing caregiver responsibilities.
AB  - OBJECTIVES: This study sought to describe the characteristics of HIV-infected
      persons who delay medical care for themselves because they are caring for others.
      METHODS: HIV-infected adults (n = 2864) enrolled in the HIV Cost and Services
      Utilization Study (1996-1997) were interviewed. RESULTS: The odds were 1.6 times
      greater for women than for men to put off care (95% confidence interval [CI] =
      1.2, 2.2); persons without insurance and with CD4 cell counts above 500 were also
      significantly more likely to put off care. Having a child in the household was
      associated with putting off care (odds ratio [OR] = 1.8, 95% CI = 1.4, 2.3).
      CONCLUSIONS: Women or individuals with a child in the household should be offered
      services that might allow them to avoid delays in seeking their own medical care.

PMID- 10897197
TI  - Scientific silence: AIDS and African Americans in the medical literature.

PMID- 10897196
TI  - Self-reports of induced abortion: an empathetic setting can improve the quality
      of data.
AB  - OBJECTIVES: This study estimated the proportion of incomplete abortions that are
      induced in hospital-based settings in Tanzania. METHODS: A cross-sectional
      questionnaire study was conducted in 2 phases at 3 hospitals in Tanzania. Phase 1
      included 302 patients with a diagnosis of incomplete abortion, and phase 2
      included 823 such patients. RESULTS: In phase 1, in which cases were classified
      by clinical criteria and information from the patient, 3.9% to 16.1% of the cases
      were classified as induced abortion. In phase 2, in which the structured
      interview was changed to an empathetic dialogue and previously used clinical
      criteria were omitted, 30.9% to 60.0% of the cases were classified as induced
      abortion. CONCLUSIONS: An empathetic dialogue improves the quality of data
      collected among women with induced abortion.

PMID- 10897198
TI  - Prevention counseling for HIV-negative persons.

PMID- 10897199
TI  - Condom promotion in microbicide trials.

PMID- 10897200
TI  - Condom counseling in microbicide testing: a right of choice.

PMID- 10897201
TI  - Ethics require the inclusion of condoms and counseling in anti-HIV microbicide
      trials.

PMID- 10897202
TI  - Microbicide research and "the investigator's dilemma".

PMID- 10897203
TI  - Further thoughts about vaginal microbicide testing.

PMID- 10897204
TI  - [Non-myeloablative stem cell transplant].
AB  - Myeloablation and immunosuppression were considered to be the two major roles of
      the conditioning regimens for allogeneic stem cell transplantation to facilitate
      engraftment. It has turned out, however, that immunosuppression is more important
      and myeloablation is not necessary for engraftment. At the same time, it is
      considered that the major anti-tumor effect of allogeneic stem cell
      transplantation depends on the graft-versus-leukemia effect, not on the
      conditioning regimen itself. In patients with CML who relapsed after allogeneic
      transplantation, for example, infusion of donor lymphocytes can induce a second
      complete remission. Non-myeloablative stem cell transplantation (NST) was
      developed in the late 90s based on these theories. Low-dose, less toxic, so
      called "non-myeloablative" preparative regimens have been designed not to
      eradicate the malignancies, but to provide sufficient immunosuppression to allow
      donor cells to engraft, while the graft-versus-malignancy effects eradicate the
      tumor. This strategy permits allogeneic transplantation to be used in patients
      who are not eligible for conventional, often myeloablative, transplantation
      because of advanced age or organ dysfunction. Non-myeloablative preparative
      regimens contain purine analogs, such as fludarabine or cladribine. The NST
      regimen being used at the National Cancer Center Hospital, Tokyo, Japan, consists
      of cladribine (0.11 mg/kg x 6 days), busulfan (4 mg/kg x 2 days) and rabbit anti
      thymocyte globulin (2.5 mg/kg x 4 days). We enrolled 6 patients in this NST
      protocol so far: 1 with severe aplastic anemia (sibling-PBSCT), 2 with MDS-RA (1
      for sibling-PBSCT and 1 for matched uBMT), 1 with AML-CR2 (matched uBMT), 1 with
      AML-CR3 (sibling-PBSCT), and 1 with relapsed AML (mismatched related PBSCT). All
      patients achieved engraftment within 14 days with complete donor chimerism. In
      addition to leukemias, a graft-versus-malignancy effect was also reported in
      allogeneic NST of solid tumors, such as renal cell carcinoma and malignant
      melanoma. The long-term efficacy of NST remains to be determined, and further
      clinical trials are warranted.

PMID- 10897205
TI  - [Cancer research avenues paved from oblivion].

PMID- 10897206
TI  - [Possible clinical application of immunochemotherapy experimented in animals].
AB  - The author has been investigating the value of combination chemotherapy in order
      to augment the effects of immunotherapy (biotherapy) for experimental tumors in
      animals. The accumulated evidence from experimental immunochemotherapy is briefly
      reviewed in this paper; for example, low-dose chemotherapy not only reduced tumor
      burden but also brought about immunological effects such as restoration of anti
      tumor immune responses. The paper also contains a summary of the immune escape
      mechanisms frequently observed in tumor-bearing hosts. Clinically, immunotherapy
      is generally applied to cancer patients in order to overcome the immune escape
      mechanisms and restore the immune responses to tumor cells. It is hard to expect,
      however, that the various strategies of cancer immunotherapy which show strong
      immunological effects in immunocompetent hosts would overcome the immune escape
      mechanisms in tumor-bearing hosts. The combined use of chemotherapy enhanced the
      effects of immunotherapy in the experiments. The author suggests that low-dose
      chemotherapy can augment the immune responses to tumor cells by overcoming the
      immune escape mechanisms in tumor-bearing hosts. Other findings presented are
      that the activity of immunosuppressor T cells or the production of an immuno
      suppressive cytokine, TGF-beta, by tumor cells could be selectively inhibited by
      low-dose chemotherapy. On the basis of such evidence in animal experiments, the
      author presents his proposals for clinical cancer treatments.

PMID- 10897207
TI  - [Reevaluation of immunopotentiation therapy for cancer].
AB  - Various cancer immunotherapies are thought to be insufficient to suppress cancers
      by themselves. Thus, they are usually applied in cancer therapy as an
      immunopotentiator in combination with chemotherapy. However, chemotherapy itself
      seems to be hazardous for activated immune cells. On the other hand,
      immunotherapy after surgical treatment for cancer patients of stages I through
      III significantly reduced cancer deaths compared to historical control data for
      the same surgeon team. Some lymph node metastases are cured by immunotherapy
      after resection of the main tumors. The potential of immunocancer therapy and
      problems in the future development of new cancer therapies are discussed.

PMID- 10897208
TI  - [Genetic diagnosis and construction of its system--importance of the individual
      characteristics of cancer].
AB  - Genetic diagnosis is necessary to correct mistaken cancer therapy. Today, the
      human genome project is rapidly progressing, and genetic diagnosis is also
      growing more diversely. To make genetic diagnosis truly useful in the treatment
      of cancer patients, we need to establish a new system which gives real benefit to
      the patient. One way to make such a system is based on the idea of focusing on
      the proper characteristics of individual cancers. In addition, we should never
      forget that the surgically resected tissue reflects the spirit and life of the
      patient.

PMID- 10897209
TI  - [Conceptual changes in cancer chemotherapy--biochemical modulation of 5-FU].
AB  - Recently, the demand for more useful therapies for cancer patients has increased.
      We describe in this paper a therapeutic modality based on a self-rescuing concept
      (SRC), and which features dual activity, i.e., an effect-enhancing activity and
      an adverse reaction-reducing activity. We present the theory and practice of S-1,
      a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer
      activity and reduce gastrointestinal toxicity through the deliberate combination
      of the following components: the oral fluoropyrimidine agent tegafur; a DPD
      inhibitor (CDHP) which is more potent than uracil, which is used in UFT; and an
      ORTC inhibitor (Oxo) which localizes in the gastrointestinal tract. S-1 is a
      combination drug with a molar ratio of 1:0.4:1 in FT, CDHP, and Oxo,
      respectively. A clinical pharmacology study was conducted to examine blood
      concentrations of 5-FU after twice-a-day administration of S-1 at a dose of 40
      mg/m2. Blood concentrations of 5-FU were found to be 60 to 200 ng/ml in all
      twelve patients examined. The overall response rate was 44.6% (45/101). In
      addition, the incidence of adverse reactions judged to be grade 3 or higher was
      10% or less. We have also reported a combination therapy with 5-FU (civ) (5-FU:
      250 to 350 mg/body, 24-hour cvi, consecutive days) and low-dose cisplatin (CDDP:
      3 to 5 mg/body, i.v., 5 days/week), in which CDDP was used as a modulator of 5
      FU. Low-dose FP therapy provided response rates as high as 40 to 60% in 163
      patients with various gastrointestinal cancers other than pancreas cancer. The
      incidence of the adverse reactions of nausea and vomiting which were judged to be
      grade 3 or higher was 2.5% (4/163). The incidences of other adverse reactions
      were 1% or less. In line with the theory and practice of combination therapy with
      5-FU (cvi) 24 hr cvi; 5-FU: 750 to 1,000 mg/body/day on Monday, Wednesday, and
      Friday (withdrawal on Tuesday, Thursday, Saturday and Sunday) intermittent
      administration and low-dose CDDP (3 to 5 mg/body/day day 1-5/w) consecutive
      administration was utilized in which there was a difference in cell cycle between
      gastrointestinal mucosal cell and tumor cell, or between bone marrow cell and
      tumor cell. Few adverse reactions, e.g., diarrhea and stomatitis, were observed
      despite the overall response rate being as high as 52.4% (22/42). The incidence
      of adverse reaction judged to be grade 3 or higher was as low as 9.3% (5/54),
      with an incidence of 9.3% (5/54) in Grade 3 or higher myelotoxicity. We intend in
      the future to combine the abovementioned therapeutic modalities, which provoke
      fewer adverse reactions and are easy on patients with cancer in an effort to
      further increase their life expectancy.

PMID- 10897210
TI  - [Mismatches in the treatment for gastric cancer and their correction].
AB  - Mismatches in the treatment of gastric cancer to date in Japan are as follows: 1.
      Difference in the definitive pathological diagnosis even among well-known,
      experienced pathologists. The case of a patient who was successfully treated by
      the authors is reported in this paper. 2. The insufficient number of medical
      oncologists for gastric cancer. 3. The administration of adjuvant chemotherapy
      after surgery without obvious evidence that it is needed. 4. Inadequate
      preventive measures, i.e. refrainment from smoking and eradication of
      Helicobacter pylori. 5. The application of standard surgery, which is designed
      basically to treat advanced gastric cancer with serosal and nodal involvement, in
      cases of early gastric cancer. These mismatches have been corrected recently by
      the adoption of modified surgery and an endoscopic approach to the early gastric
      cancer. These modifications could be attained through our pioneering effort to
      find a balance between the two contradictory approaches of radical treatment and
      preservation of organic function, which are often irreconcilable in cancer
      treatment in general, after the accumulation of sufficient data on early gastric
      cancer in a Japanese nationwide study.

PMID- 10897211
TI  - [The clinical effect of low-dose FP (5-FU + low-dose CDDP) in patients with far
      advanced gastric cancer, and their quality of life].
AB  - Low-dose FP therapy was carried out in 30 patients with far advanced gastric
      cancer and assessed according to anti-tumor effect and quality of life (QOL).
      This therapy consisted of CDDP (3.5-7 mg/m2/day infused on Days 1-5 every week)
      and continuous infusion of 5-FU (250 mg/m2/day for 28 days). A partial response
      was observed in 15 cases, so the overall response rate was 50%. The response
      rates with stomach and lymph node cancers were higher than those of other organs
      (64.3% and 55.6%). Patients without peritoneal dissemination, with good
      performance status (PS) (0, 1) and differentiated histologic type showed a
      significantly higher response rate than patients with peritoneal dissemination,
      poor PS (2, 3, 4) and undifferentiated histologic type (p = 0.0034, 0.0253,
      0.0080). No side effects (> or = WHO grade 3) were observed. The QOL of patients
      was assessed according to the percentage of patients with an observed improvement
      of diet, who could be discharged from hospital, and the duration in hospitals in
      relation to survival time (hospital stay). The QOL of patients with low-dose FP
      therapy was better than that of patients with usual combination chemotherapy. Low
      dose FP therapy is a promising regimen for patients with far advanced gastric
      cancer.

PMID- 10897212
TI  - [Biweekly low-dose cisplatin and 5-fluorouracil combination chemotherapy for
      advanced gastrointestinal carcinoma].
AB  - Biweekly intravenous infusions of low-dose cisplatin (CDDP) and 5-fluorouracil (5
      FU) were evaluated in 80 patients with advanced or recurrent gastric, colorectal,
      pancreatic or gallbladder adenocarcinoma. CDDP was given biweekly at a dose of 15
      mg/m2 infused for 30 minutes, and 5-FU 375 mg/m2 was infused for 2 hours as many
      times as possible. The response rate among patients with gastric cancer was 26%,
      colorectal cancer 10%, pancreatic cancer 7.7%, and gallbladder cancer 42.9%. The
      response rates were not so high, but the median survival time of patients with
      recurrent gastric cancer was 17.3 months, pancreatic cancer 6.7 months, and
      gallbladder cancer 10.7 months. A patient with unresected advanced pancreatic
      head cancer with liver and para-aortic lymph node metastases received this
      therapy 38 times, and lived for 54 months. No severe side effects occurred in any
      of these cases. Thus, this chemotherapy could well be effective for the outcome
      of cases of advanced gastrointestinal carcinoma.

PMID- 10897213
TI  - [Peripheral blood stem cell harvest in patients with limited stage small-cell
      lung cancer].
AB  - Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced
      mobilization of peripheral blood stem cells (PBSC) was performed in patients with
      limited stage small-cell lung cancer. Chemotherapy consisted of
      cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34
      positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected
      during 2-3 courses of apheresis were 3.1 +/- 2.9 x 10(6)/kg (n = 10) and 3.1 +/-
      1.5 x 10(5)/kg (n = 8), respectively. Adequate amounts of PBSC were also
      harvested even in patients treated with concurrent chemoradiotherapy. Eight
      patients were successfully treated with high-dose chemotherapy consisting of
      ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone
      marrow reconstruction was rapid and no treatment-related death was observed.

PMID- 10897214
TI  - [In vitro growth and clinical response of leukemia cells to macrophage colony
      stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF) in
      acute leukemia].
AB  - The in vitro growth and clinical response of leukemia cells to macrophage colony
      stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF) were
      studied in 24 patients with acute leukemia. Among cases of acute myelogenous
      leukemia, a positive response to M-CSF (stimulation index > or = 2.5) was seen in
      27.3% of the cases, and a significantly higher response rate (81.8%) was seen
      following G-CSF treatment of leukemia cells in vitro. In cases of acute monocytic
      leukemia, M-CSF showed a higher stimulating index than that observed for non
      monocytic leukemia. G-CSF was administered in 19 cases and M-CSF in 5 cases after
      chemotherapy, and none of the patients showed leukemia cell proliferation in
      vivo. There was no correlation between in vitro test results and clinical
      response of leukemia cells to the CSFs administered.

PMID- 10897215
TI  - [Clinical significance of serum p53 antibody detection in a chemosensitivity
      assay in cases of human colorectal cancer].
AB  - Alteration of the p53 gene product occurs frequently during the progression of
      colorectal cancer. Recently, mutated p53 protein was found to induce the
      production of anti-p53 antibodies in the serum of patients. The purpose of this
      study was to evaluate the relationship between p53 status in serum and
      chemosensitivity in resectable colorectal cancer patients. A total of 35 patients
      with primary colorectal cancer who underwent surgical treatment were examined by
      chemosensitivity test with the viable tumor samples using Histoculture Drug
      Response Assay (HDRA). Serum samples of these patients to test for p53 antibodies
      were obtained before tumor resection, and assayed in duplicate by using an enzyme
      linked immunosorbent assay (ELISA) kit. The inhibition index of 5-FU and CDDP,
      determined by the HDRA method, in the sero-positive group was significantly lower
      than that of the sero-negative group (p < 0.01). Furthermore, significant
      statistical differences in chemosensitivity to 5-FU and CDDP were revealed
      depending on the presence of serum p53 antibodies. There was no relationship
      between chemosensitivity assay and tumor marker positivity or clinicopathological
      features in these patients. Detection of serum p53 antibodies, which reflects p53
      mutations in tumor tissue, is a simple method which correlates with
      chemosensitivity, and may contribute to the selection of favorable
      chemotherapeutic strategies of colorectal cancer.

PMID- 10897216
TI  - [Comparison of pharmacokinetics of 5-FU and alpha-fluoro-beta-alanine, a
      metabolite of 5-FU, in plasma after administration of UFT, tegafur, 5-FU or
      doxifluridine to rats].
AB  - Toxic effects (neurotoxicity and cardiotoxicity) of 5-FU and its derivatives have
      been reported by many investigators. These toxicities are considered to be caused
      by the inhibition of the TCA cycle by alpha-fluoro-beta-alanine (FBAL), a
      metabolite of 5-FU, and later metabolites. In this study, we focused on FBAL as
      an index of the above toxicities. We compared the concentrations of 5-FU and FBAL
      in plasma after administration of UFT, tegafur (FT), 5-FU or doxifluridine (5'
      DFUR) to rats (75 mumol/kg) in order to evaluate which compound has the better
      balance of efficacy and toxicity. UFT exhibited the lowest FBAL concentration in
      plasma followed by FT, 5'-DFUR and 5-FU. The ratio of FBAL to 5-FU in Cmax and
      AUC after dosing of UFT was the lowest among these four test compounds. These
      data indicate that the lowest ratio of FBAL to 5-FU resulted from the inhibitory
      effect of uracil, a component of UFT, on the metabolism of 5-FU. In conclusion,
      the present results suggest that UFT has a better balance of efficacy and
      toxicity than FT, 5-FU and 5'-DFUR.

PMID- 10897217
TI  - [Expression of recombinant human dihydropyrimidine dehydrogenase and its
      application to the preparation of anti-DPD antibodies for immunochemical
      detection].
AB  - Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the catabolism of 5
      fluorouracil (5-FU), and its expression in a tumor is thought to reduce the
      efficacy of 5-FU against the tumor. To detect a DPD molecule by immunoblotting
      and/or immunohistochemical methods, we attempted to prepare highly specific
      antibodies against recombinant human DPD (rhDPD) expressed in the baculovirus
      expression system using hDPD cDNA. The expressed rhDPD protein was found to
      retain its entire molecular form and to show a high 5-FU-degrading activity
      equivalent to that of human liver DPD. Using this recombinant protein, both
      monoclonal and polyclonal antibodies to ehDPD were generated and their
      specificities, relationship to enzyme activity and the possibility of
      immunohistochemical measurement of tumoral DPD expression were investigated. The
      results revealed that anti-rhDPD monoclonal antibodies recognized only human DPD,
      while anti-rhDPD polyclonal antibodies reacted with both human and rodent DPD.
      The DPD content in 26 tumor cells, estimated by immunoblotting, was closely
      related to the 5-FU-degrading activities in those cells (r = 0.874). Moreover,
      immunohistochemical evaluation of tumor cellular DPD expression using our anti
      rhDPD antibodies revealed that tumor cells expressing high levels of DPD showed
      strongly positive staining, but not those expressing low level or no DPD. These
      results suggest that immunochemical detection of tumoral DPD expression using our
      anti-rhDPD antibodies may be a means to predict the clinical response to 5-FU
      based chemotherapy.

PMID- 10897218
TI  - [A case of advanced esophageal carcinoma successfully treated with chemoradiation
      therapy with low-dose cisplatin and 5-fluorouracil].
AB  - We have experienced a case of advanced esophageal carcinoma successfully treated
      with chemoradiation therapy together with low-dose cisplatin and 5-fluorouracil,
      having only minor toxicity. A 55-year-old man was admitted to our hospital
      because of dysphagia. Cervical esophageal carcinoma was found to have invaded the
      larynx through endoscopy, and invasion to thyroid gland and trachea was suspected
      from a cervical CT. We diagnosed the condition as advanced esophageal carcinoma
      (A2N(-)M0Pl0 Stage III). We then treated the patient by chemoradiation therapy.
      After the treatment, the carcinoma could not be detected by CT and endoscopy, and
      endoscopic biopsy revealed there were no active carcinoma cells. The side effects
      of the therapy were very mild, therefore the patient could be discharged after a
      short time. No evidence of a tumor relapse was found 5 months after the therapy.
      We treated 4 patients with esophageal carcinoma using the same regimen, and the
      results of the therapy were 2 CR, 1 PR, and 1 PD, with an overall response rate
      of 75%.

PMID- 10897219
TI  - [A case of nonresectable scirrhous type gastric cancer successfully treated by
      low-dose cisplatin (CDDP), 5-fluorouracil (5-FU) and pirarubicin (THP)].
AB  - There have been few effective chemotherapeutic regimens for scirrhous type
      gastric cancer. Recently, the usefulness of combined cancer agent chemotherapy
      based on the concept of biochemical modulation has been reported. For example
      sequential MTX and 5-FU therapy, low-dose CDDP plus 5-FU, and the like. In this
      paper, we report the usefulness of low-dose CDDP plus 5-FU therapy in combination
      with pirarubicin (THP) for inoperable scirrhous type gastric cancer. A 32-year
      old man who was suffering from scirrhous type gastric cancer with pyloric
      stenosis was treated with this regimen. Eight weeks after the start of therapy,
      his gastric capacity and lumen diameter had clearly increased, and he was taking
      ordinary meals. Ascites had also completely disappeared. CR has now been
      continued about 7 months. This regimen is considered to be promising for
      scirrhous type gastric cancers with a poor prognosis.

PMID- 10897221
TI  - [Weekly low-dose CPT-11 and HCFU for advanced colorectal cancer on an outpatient
      treatment basis].
AB  - We attempted a new outpatient treatment using weekly low-dose CPT-11 for advanced
      colorectal cancer patients. A 73-year-old female with para-aortic lymph node
      metastases from advanced rectal cancer was given outpatient treatment for more
      than 5 months with weekly low-dose CPT-11 and HCFU. CPT-11 was given
      intravenously at a dose of 20 mg/m2 on day 1 every week. On days 2-7, she was
      treated by oral administration of HCFU (600 mg). Her serum CEA level decreased
      and continued to do so for more than 5 months. The size of the para-aortic lymph
      node was reduced by approximately 40%. There were no adverse effects except
      leukopenia (grade 2). These results suggest that weekly low-dose CPT-11 and oral
      HCFU may be an effective therapy on an outpatient basis in cases of advanced
      colorectal cancer.

PMID- 10897220
TI  - [A case of gastric cancer with multiple liver metastasis responding to combined
      chemotherapy with low-dose cisplatin and 5-fluorouracil].
AB  - A 68-year-old man who had Borrmann type 4 gastric cancer with multiple liver
      metastases was admitted to our hospital on October 20, 1998. He was considered
      nonresectable and placed on neoadjuvant chemotherapy consisting of low-dose CDDP
      and 5-FU. After 9 weeks of administration, the liver metastases had disappeared
      on abdominal computed tomography, but the primary lesion had progressed. On May
      12, 1999, a total gastrectomy with a partial resection of the transverse colon
      and resectional biopsy of a white nodule of the liver were performed. This was a
      non-curative operation because of the peritoneal dissemination. A
      histopathological examination of the liver nodule revealed that the cancer cells
      had disappeared. The patient had an uneventful postoperative course and 4 weeks
      of chemotherapy were added. He remains alive with no symptoms or re-growth of the
      liver metastatic tumor 4 months after the surgery.

PMID- 10897222
TI  - [Malignant pheochromocytoma with remarkable response to CVD chemotherapy--a case
      report].
AB  - A 60-year-old man was admitted to our hospital with the chief complaint of a left
      upper abdominal mass. 131I-MIBG scintiscan revealed a left upper abdominal mass,
      and the patient's serum catecholamine level was very high. Our diagnosis was
      pheochromocytoma of the left adrenal gland. On Oct. 19, 1995, a left nephrectomy
      and adrenectomy were performed. The serum catecholamine level then decreased and
      blood pressure was normalized. Two years later, it became difficult to control
      the patient's hypertension, and multiple metastatic liver cancer was found by an
      abdominal CT scan. The diagnosis of malignant pheochromocytoma was confirmed by
      the accumulation of 131I-MIBG in the liver. We started CVD chemotherapy. After 10
      cycles of this chemotherapy, the serum catecholamine level was almost normalized
      and the metastatic liver cancer was reduced to one-third in size.

PMID- 10897223
TI  - [Current problems of early phase clinical trials for new anticancer agents in
      Japan].
AB  - The agreement of the International Conference of Harmonization (ICH) states that
      any pharmaceutical company shall be able to apply for new drug applications in
      any country or area. The new version of Good Clinical Practice (GCP) has changed
      the principal process and structure of clinical development of new drugs, and
      most medical institutions have experienced many difficulties in adapting to the
      new version of GCP. Pharmaceutical companies have moved the main area of
      investigation for their new drugs from Japan to Europe or the United States, and
      have decreased the number of early phase clinical trials in Japan. If this
      situation continues in Japan for long, it will without doubt cause a decline in
      the level of medical practice here. We must make efforts to establish a total
      system for the clinical development of anticancer agents in Japan, and maintain a
      place for young Japanese medical oncologists to participate actively in the
      establishment of effective new treatments for cancer patients.

PMID- 10897224
TI  - The case for drug testing.

PMID- 10897225
TI  - Should the government allow genes to be patented?

PMID- 10897226
TI  - Going ... going ... gone?

PMID- 10897227
TI  - A new era in outpatient care.

PMID- 10897228
TI  - A modern marriage.

PMID- 10897229
TI  - Establishment of phase I trials in Israel.

PMID- 10897230
TI  - Behavior of patients with flu-like symptoms: consultation with physician versus
      self-treatment.
AB  - BACKGROUND: The reasons that patients consult the clinic physician for common
      minor symptoms are not clearly defined. For seasonal epidemic events such as flu
      like symptoms this characterization is relevant. OBJECTIVES: To identify the
      factors that prompt patients to seek medical attention, and correlate patient
      behavior with different demographic and disease variables. METHODS: A random
      sample of 2,000 enrolled people aged 18-65 years and registered with eight
      primary care clinics located throughout Israel were asked to report whether they
      had had flu-like symptoms within the previous 3 months. Those who responded
      affirmatively (n = 346) were requested to complete an ad hoc questionnaire
      evaluating their treatment-seeking behavior. RESULTS: A total of 318 patients
      completed the questionnaire (92% response rate), of whom 271 (85%) consulted a
      physician and 47 (15%) did not. Those who sought medical assistance had more
      serious symptoms as perceived by them (cough, headache and arthralgia) (P <
      0.05), and their main reason for visiting the doctor was "to rule out serious
      disease." Self-employed patients were more likely than salaried workers to visit
      the clinic to rule out serious disease (rather than to obtain a prescription or
      sick note or to reassure family). They also delayed longer before seeking
      treatment (P = 0.01). CONCLUSION: In our study the majority of individuals with
      flu symptoms tended to consult a physician, though there were significant
      variations in the reasons for doing so, based on a combination of
      sociodemographic variables. We believe these findings will help primary care
      physicians to characterize their practices and to program the expected demand of
      flu-like symptoms.

PMID- 10897231
TI  - Demographic characteristics of patients with community-acquired bacteriuria and
      susceptibility of urinary pathogens to antimicrobials in northern Israel.
AB  - BACKGROUND: Urinary tract infection is one of the most common bacterial
      infections. Since antibiotics are given empirically, it is necessary to assess
      the distribution and susceptibility of the microorganisms in each case.
      OBJECTIVES: To evaluate the demographic characteristics of ambulatory patients
      with UTI, the distribution and susceptibility of uropathogens, and the risk
      factors associated with trimethoprim-sulfamethoxazole resistant bacteria in
      women. METHODS: During 12 days in August 1997 all the urine cultures sent to the
      Tel-Hanan Laboratory (Haifa) were evaluated. Demographic characteristics of the
      patients, their underlying diseases and the previous use of antibiotics were
      obtained. RESULTS: During the 12 day survey 6,495 cultures were sent for
      evaluation. Of the 1,075 (17%) that were positive 950 were included in the study;
      83.7% were from females, of whom 57% were > or = 50 years old. Escherichia coli
      was the most common pathogen, with 74.7% in the female and 55% in the male
      population; 86.2% of the E. coli were resistant to amoxicillin, 38.8% to
      cephalexin and 46.8% to TMP-SMX. Cefuroxime (4.2%), ofloxacin (4.8%),
      ciprofloxacin (4.8%) and nitrofurantoin (0.4%) showed the lowest rates of
      resistance. By a multivariant analysis, post-menopause and recurrent UTI were
      found to be independent factors related to TMP-SMX resistance in women.
      CONCLUSION: In northern Israel, ampicillin, cephalexin and TMP-SMX cannot be used
      empirically in the treatment of community-acquired UTI. Post-menopause and
      recurrent UTI are independent factors associated with TMP-SMX resistant pathogens
      in women.

PMID- 10897232
TI  - The natural course of upper gastrointestinal submucosal tumors: an endoscopic
      ultrasound survey.
AB  - BACKGROUND: Differentiating between benign and malignant submucosal tumors is
      difficult. Moreover, the natural course of benign-appearing SMTs is not clearly
      elucidated. OBJECTIVES: To evaluate the natural course of upper gastrointestinal
      SMTs by endoscopic endosonography. METHODS: We followed 25 consecutive patients
      with small (< 40 mm) SMTs for a mean period of 19 months. Evaluation included
      maximal tumor diameter, internal echo pattern, and outer margin of lesions.
      RESULTS: Follow-up revealed no change in echo features in 24 of 25 patients
      (96%). In only one patient a homogenous hypoechoic smooth margin lesion converted
      to a non-homogenous tumor with an irregular outer margin. This lesion also
      increased in size from 30 to 38 mm. On surgical removal this tumor was found to
      be a stromal tumor with high malignant potential. CONCLUSIONS: Most small SMTs do
      not change during a period of 19 months and a conservative policy of surveillance
      is warranted.

PMID- 10897233
TI  - Rheumatic fever in the Nazareth area during the last decade.
AB  - BACKGROUND: Acute rheumatic fever is considered a relatively uncommon disease in
      developed countries. Although cases are encountered in the Nazareth area in
      Israel, no systematic study of this disease has been done in the last 20 years.
      OBJECTIVE: To study the incidence and characteristics of acute rheumatic fever
      cases in the Nazareth area during the last decade. METHODS: Cases of acute
      rheumatic fever diagnosed according to the modified Jones criteria were
      identified in two hospitals in the Nazareth area during the 10 years. These two
      hospitals receive about 75% of non-obstetric referrals to the emergency room.
      Clinical, laboratory and treatment data of these patients were documented and the
      incidence of disease calculated. The population census in the Nazareth area was
      obtained from the Central Bureau of Statistics. RESULTS: Forty-four patients,
      with a mean age of 18 years, were identified. The mean annual incidence was 5
      cases/100,000 population. Arthritis was found in 98% of the patients (migratory
      in 52%) and carditis in 34%, but only one patient had a subcutaneous nodule, and
      none had either erythema marginatum or chorea. Only one patient with carditis
      developed heart failure a few months later due to severe mitral stenosis.
      CONCLUSION: Rheumatic fever in the Nazareth area is still manifest. The mean age
      of the patients was higher than found previously. In only half of the patients
      was the arthritis migratory, with other major manifestations of rheumatic fever
      found only rarely.

PMID- 10897234
TI  - Patients' perceptions of drug therapy counseling in Israel.
AB  - BACKGROUND: The more patients know about their medications the higher their
      compliance with drug therapy, reflecting an effective communication between
      health professionals and their patients. Numerous studies on this subject have
      been published, but none has been conducted in Israel. OBJECTIVES: To evaluate
      patients' perceptions of drug counseling by health professionals--the prescribing
      physician and dispensing pharmacist--and to determine whether there is a
      difference in the patient's perception according to his or her place of birth and
      mother tongue. METHODS: A total of 810 patients were interviewed following
      receipt of their medications from in-house pharmacies at two community clinics of
      Israel's largest sick fund. Each patient was interviewed in his or her mother
      tongue according to a constructed questionnaire, which included the patient's
      demographic background, type of medications received, the patient's perceptions
      of drug counseling given by both the physician and the pharmacist, and the
      patient's perception of non-prescription drug counseling given by the dispensing
      pharmacist. RESULTS: Of the 810 patients enrolled in this study, 32% received
      three or more medications at each physician visit. The main therapeutic classes
      of medications prescribed and dispensed were for neurological disorders,
      cardiovascular diseases, gastrointestinal problems and respiratory diseases.
      While 99% of the patients claimed that they knew how to use their medications,
      only 96% reported receiving an explanation from either physician or pharmacist.
      The quality of counseling, as evaluated by the patients, was ranked above average
      for 75% of the consultations with the prescribing physician and 63% with the
      dispensing pharmacist. CONCLUSIONS: Although few conclusions can be drawn from
      this study based on the initial statistical analysis of the data, the major
      findings were that patients value highly the counseling they receive and that 99%
      believe they have the requisite knowledge for using their medications. Compared
      to the international literature, our results--based on the patients' perceptions-
      indicate that counseling by pharmacists is a common and well-accepted activity in
      Israel and occurs at a high rate.

PMID- 10897235
TI  - Pediatric emergency room response to community pediatricians' expectations.
AB  - BACKGROUND: In Israel the pediatric emergency room functions as an urgent primary
      care clinic in addition to dealing with life-threatening situations. Due to
      health insurance stipulations, most patients come to the PER with a referral from
      the community clinic. The relationship between the referring physician's
      expectations and the subsequent management of the referred patient in the PER is
      not well defined. OBJECTIVES: To evaluate the relationship between the
      expectations of the primary care physician and the management of referred
      patients in the PER, assess the type of information provided by the referring
      physician, and examine the effect of additional information obtained from the
      referring physician on patient management in the PER. METHODS: We reviewed the
      records of patients presenting at the PER with referrals from primary care
      physicians as well as additional information obtained by telephone interviews
      with the referring physicians. RESULTS: The expectations of the referring
      physicians were not fully documented in the referral form. The PER responded to
      the patient as if the PER was the initial contact. There was no significant
      difference in the response of PER physicians with or without additional
      information from the referring physicians. CONCLUSIONS: The PER acts as an
      independent unit with no obligation to satisfy the expectations of the referring
      physicians. The relationship between the PER and the referring physicians needs
      to be clarified. Guidelines and structured PER referral forms should be
      implemented in all primary care clinics to improve patient management and
      communication between health providers.

PMID- 10897236
TI  - Smoking and first acute myocardial infarction: age, mortality and smoking
      cessation rate.
AB  - BACKGROUND: Cigarette smoking is a major contributor to the risk of acute
      myocardial infarction and the subsequent morbidity and mortality. Physicians can
      play an important role in smoking cessation among patients with AMI because of
      their frequent contact with the patient during the event. OBJECTIVES: To study
      the prevalence of smoking, age, localization of coronary occlusion, mortality and
      rate of smoking cessation in consecutive patients who were diagnosed with a first
      AMI in our center in 1989-93. METHODS: The study included 1,510 consecutive
      patients with first AMI: 973 men (512 smokers, 52.6%) and 537 women (215 smokers,
      40%), whose mean age was 64.1 +/- 6.7 and 68.6 +/- 5.2 years respectively.
      RESULTS: The median age at the first AMI in non-smoking and smoking men differed
      significantly (70.4 +/- 6.8 vs. 56.6 +/- 6.1 years, P < 0.001) while the
      difference in the women was smaller (70.4 +/- 6.9 vs. 66.8 +/- 7.2). The
      proportion of smokers/non-smokers among men was greater at a younger age and
      decreased proportionally with age. The overall mortality was 11.3% with a
      significant difference in mortality rate in the younger age groups between
      smokers and non-smokers (1% vs. 0% in the age group 31-40 years, P < 0.05, and
      6.1% vs. 0.8% in the 41-50 year age group, P < 0.001). Only 62% of the smokers
      who survived the AMI declared that they had received anti-smoking advice from a
      physician during hospitalization. The cessation rate in this group was
      significantly higher than in smokers who had not been cautioned against smoking
      (56% vs. 18%). CONCLUSIONS: Current smokers sustained their first AMI more than
      one decade earlier than non-smokers, and the younger smokers had a higher
      mortality rate. The majority of the smokers who received anti-smoking advice
      during their hospitalization for AMI quit smoking in the year following the acute
      event.

PMID- 10897238
TI  - The role of functional neurosurgery in Parkinson's disease.

PMID- 10897237
TI  - The influence of aprotinin on myocardial function after liver ischemia
      reperfusion.
AB  - BACKGROUND: The beneficial effect of aprotinin, a naturally occurring protease
      inhibitor, on preservation of organs such as the liver, kidney and lung has been
      documented. OBJECTIVE: To explore the effects of hepatic ischemia and reperfusion
      on both liver and myocardial function, using a dual isolated perfused organ model
      with and without aprotinin. METHODS: Isolated rat livers were stabilized for 30
      minutes with oxygenated modified Krebs-Henseleit solution at 37 degrees C. Livers
      were then perfused continuously with KH or KH + aprotinin 10(6) KIU/L for an
      additional 135 min. Livers of two other groups were made globally ischemic for
      120 min, then perfused for 15 min with KH or with KH + aprotinin. Isolated hearts
      (Langendorff preparation) were stabilized for 30 min and then reperfused with KH
      or KH + aprotinin exiting the liver for 15 min. The liver's circuit was
      disconnected, and hearts were re-circulated with the accumulated liver + heart
      effluent for an additional 50 min. RESULTS: In the ischemia and ischemia +
      aprotinin groups, portal vein pressure (1 and 15 min reperfusion) was 331 +/- 99%
      and 339 +/- 61% vs. 308 +/- 81% and 193 +/- 35% of baseline, respectively (P <
      0.03 vs. ischemia). There were no other differences in the enzyme leakage between
      aprotinin-treated or untreated ischemic livers. Left ventricular pressure was
      stable in the controls. However, LV pressure in groups perfused with ischemic
      liver effluent declined within 65 min reperfusion, whether aprotinin treated or
      not (84 +/- 8% and 73 +/- 5% of baseline, respectively, P < 0.004 only for
      ischemia vs. control). CONCLUSION: When aprotinin was used, LV pressure was
      inclined to be higher while liver portal vein pressure was lower, thus providing
      protection against liver and heart reperfusion injury.

PMID- 10897239
TI  - Systemic lupus erythematosus and antiphospholipid syndrome during pregnancy:
      maternal and fetal complications and their management.

PMID- 10897240
TI  - Genomic and transcriptional characterization of the human ACHE locus: complex
      involvement with acquired and inherited diseases.
AB  - BACKGROUND: Abnormal levels of the acetylcholinesterase enzyme or aberrations
      involving the long arm of chromosome 7, harboring the ACHE gene at 7q22, occur in
      various diseases such as Alzheimer's, Parkinson's, and leukemias. However, the
      cause(s) of these abnormalities are still unknown. OBJECTIVE: To search for the
      genomic elements and transcriptional processes controlling ACHE gene expression
      and the plausible stability of its locus, by isolating, sequencing and
      characterizing the human (h)ACHE locus and its mRNA products. METHODS: Three
      clones containing the ACHE gene were isolated from a human chromosome 7 cosmid
      library. Two of these clones were thereafter sequenced and searched for
      repetitive elements, open reading frames and corresponding expressed sequence
      tags. Reverse transcription-polymerase chain reaction was employed to further
      explore these findings. RESULTS: The locus harboring the G,C-rich ACHE gene was
      found to be exceptionally rich in Alu repeats. It includes an additional,
      inversely oriented gene (ARS), tentatively associated with arsenite resistance.
      EST clones corresponding to both genes were found in cDNA libraries from 11
      different human tissue sources, with ARS expressed in 10 additional tissues. Co
      regulation of brain ACHE and ARS was suggested from their mutually increased
      expression following acute psychological stress. CONCLUSIONS: The abundance of
      Alu retrotransposones may predispose the ACHE locus to chromosomal
      rearrangements. Additionally, coordinated transcriptional regulation is implied
      from the joint ARS-AChE expression in stress insult responses. Disease-related
      changes in AChE may therefore reflect locus-specific regulation mechanisms
      affecting multiple tissues.

PMID- 10897241
TI  - Gouty olecranon bursae.

PMID- 10897242
TI  - Penetrating neck trauma.

PMID- 10897243
TI  - The inflammation meter (INFLAMET): a new diagnostic approach to reveal the
      presence of an inflammatory response and assess its intensity.

PMID- 10897244
TI  - Phase I trials in Israel: some considerations.

PMID- 10897245
TI  - Rheumatic fever: a never-ending story?

PMID- 10897246
TI  - Successful treatment of chronic Henoch-Schonlein purpura with colchicine and
      aspirin.

PMID- 10897247
TI  - Pseudohypertension [correction of Pseudohypotension] in a patient with malignant
      hypertension.

PMID- 10897248
TI  - Pedal edema associated with clozapine use.

PMID- 10897249
TI  - New weight-reducing medication: the patient's request and the doctor's
      prescription.

PMID- 10897250
TI  - Chlamydia pneumoniae and heart.

PMID- 10897251
TI  - A review of current and future treatment strategies for malignant astrocytomas in
      adults.
AB  - BACKGROUND: For more than 20 years, after establishing the role of postoperative
      radiotherapy for malignant astrocytomas, no definitive improvement in survival
      rates could be observed, despite advances in established treatment modalities
      such as radiotherapy and chemotherapy. This review discusses available laboratory
      and clinical data as well as recent advances in our knowledge about prognostic
      factors (Table 1) and their implications for the design of future clinical
      trials. RESULTS: Elucidation of the biology of malignant astrocytomas allowed for
      development of rational new approaches, such as gene therapy and immunotherapy,
      which could interfere with established treatment regimens or being used
      independently. Possible strategies include the restoration of defective cancer
      inhibitory genes, cell transduction or transfection with antisense DNA
      corresponding to genes coding for growth factors and their receptors, or with the
      so-called suicide genes. Several antiangiogenic approaches such as administration
      of thalidomide, protamine, or monoclonal antibodies against vascular endothelial
      growth factor have been developed, too. Further treatment possibilities include
      modulation of drug resistance, e.g. by P-glycoprotein antagonists or O6-alkyl
      guanine-DNA-transferase inhibitors, inhibition of matrix metalloproteinases,
      inhibition of protein kinase C, and administration of agents such as
      phenylbutyrate or valproic acid that showed promising antiproliferative effects
      in vitro. CONCLUSIONS: Several rational new approaches are now entering clinical
      trials (Table 2). In the light of limited survival after standard treatment it is
      recommended that patients should be offered participation in such trials.

PMID- 10897252
TI  - Supratentorial low-grade glioma: results and prognostic factors following
      postoperative radiotherapy.
AB  - BACKGROUND AND PURPOSE: To assess treatment outcome and prognostic factors
      following postoperative external radiotherapy in 77 patients with low-grade
      glioma. PATIENTS AND METHODS: Between 1977 and 1996, 45 patients with
      astrocytoma, 14 with oligodendroglioma and 18 with mixed glioma received
      postoperative radiotherapy with a median total dose of 52 Gy (range, 45 to 61
      Gy). Sixty-seven patients were treated immediately following surgery, 10 patients
      with tumor progression. The influence of various factors including histology,
      gender, age, seizures, duration of symptoms (< or = 6 weeks vs > 6 weeks), CT
      pattern (enhancement vs no enhancement), type of surgery, total radiotherapy dose
      and timing of radiotherapy on relapse-free survival and overall survival was
      investigated. RESULTS: The median overall survival time was 81 months, the 5- and
      10-year survival rates were 54% and 31%, respectively. The median time to
      progression was 56 months, while the 5- and 10-year progression-free survival
      rates were 45% and 24%. Univariate analyses identified the total radiotherapy
      dose (p = 0.01), duration of symptoms (p = 0.05), the presence of seizures (p =
      0.04), and the CT pattern following intravenous contrast (p = 0.005) as
      significant prognostic factors for overall survival. Progression-free survival
      rates were influenced by the total dose (p = 0.04), the duration of symptoms (p =
      0.01) and CT pattern (p = 0.006). On multivariate analysis, only the CT pattern
      (enhancement vs no enhancement) remained as independent prognostic factors for
      both progression-free survival and overall survival. CONCLUSIONS: A minimum total
      dose of 52 Gy is recommended for the postoperative radiotherapy in low-grade
      glioma. Tumors with CT enhancement seem to need further intensification of
      treatment.

PMID- 10897253
TI  - Adjuvant and neoadjuvant radiochemotherapy in ductal pancreatic carcinoma.
AB  - BACKGROUND: Ductal pancreatic carcinoma ranks third among malignancies of the
      gastrointestinal tract and its incidence is rising. Today, patients with this
      disease still have fatal prognosis necessitating efforts towards more effective
      treatment. MATERIAL AND METHODS: This report provides a review of adjuvant and
      neoadjuvant radiotherapy in pancreatic carcinoma without distant metastasis.
      Particular respect is given to prospective, randomized trials. They are analyzed
      according to clinical staging: 1. In resectable tumors adjuvant, neoadjuvant or
      intraoperative radiotherapy is performed. 2. Radiotherapy in neoadjuvant
      intention is an approach for downstaging to achieve resectability in initially
      irresectable tumors. RESULTS: The widespread use of new techniques such as
      supervoltage irradiation, computer based 3-D-planning, interventional therapy and
      combination of different therapeutic modalities induced a great number of
      studies. When concomitant chemotherapy was added to radiotherapy, results became
      significantly better compared to exclusive radiotherapy. It is shown that
      patients with operable tumors will have better survival rates and lower risk of
      relapse, if radiochemotherapy is added to surgery. Patients with irresectable
      tumors possible can be downstaged and be brought to resection nevertheless.
      CONCLUSIONS: Simultaneous radiochemotherapy with 5-FU and mitomycin C can be
      performed without elevated risk of acute side effects of higher degree. This
      approach may be indicated in the case of adjuvant situations in patients free of
      distant metastases. Neoadjuvant simultaneous radiochemotherapy should only be
      performed as a part of a clinical trial.

PMID- 10897254
TI  - A new verification film system for routine quality control of radiation fields:
      Kodak EC-L.
AB  - BACKGROUND: The use of modern irradiation techniques requires better verification
      films for determining set-up deviations and patient movements during the course
      of radiation treatment. This is an investigation of the image quality and time
      requirement of a new verification film system compared to a conventional portal
      film system. MATERIAL AND METHODS: For conventional verifications we used Agfa
      Curix HT 1000 films which were compared to the new Kodak EC-L film system. 344
      Agfa Curix HT 1000 and 381 Kodak EC-L portal films of different tumor sites
      (prostate, rectum, head and neck) were visually judged on a light box by 2
      experienced physicians. Subjective judgement of image quality, masking of films
      and time requirement were checked. RESULTS: In this investigation 68% of 175
      Kodak EC-L ap/pa-films were judged "good", only 18% were classified "moderate" or
      "poor" 14%, but only 22% of 173 conventional ap/pa verification films (Agfa Curix
      HT 1000) were judged to be "good". CONCLUSIONS: The image quality, detail
      perception and time required for film inspection of the new Kodak EC-L film
      system was significantly improved when compared with standard portal films. They
      could be read more accurately and the detection of set-up deviation was
      facilitated.

PMID- 10897255
TI  - p53: biology and role for cellular radiosensitivity.
AB  - PURPOSE: p53 is the most commonly mutated gene in human tumors with large impact
      on cellular biology and response to radiation. Many excellent reviews are
      available on various aspects but for several years none about the role of p53 for
      radiosensitivity. The latter is the aim of the present paper. METHODS: Review of
      the literature. RESULTS: p53 is a regulator of apoptosis mainly in hematopoetic
      tissue. In normal tissue and solid tumors presumably other functions have more
      impact on the cellular response. p53 controls cell-cycle progression after
      irradiation and also DNA-repair, namely homologous and non-homologous
      recombination. Mutations of p53 alter these functions which may be responsible
      for an enhanced cellular and tumor radioresistance. At present only few reports
      were able to show that under tightly controlled conditions loss of p53 wild-type
      function leads to enhanced radioresistance. A general proof is still lacking.
      CONCLUSIONS: The emerging picture in the year 2000 shows p53 as a central protein
      in a multi-enzyme multi-function network which is far from being fully
      understood. Although p53 appears to be a major regulator it is certainly not the
      unreplaceable component the loss of which uniformly determines radioresistance.
      Only further understanding of modifiers and co-operators in the cell and in the
      specific tissue context will elucidate p53's role for radiosensitivity and
      radiotherapy.

PMID- 10897256
TI  - [Radiotherapy of hidradenitis suppurativa--still valid today?].
AB  - PURPOSE: In a retrospective analysis the efficacy of radiotherapy in the
      treatment of hidradenitis suppurativa was assessed. PATIENTS AND METHODS: Data
      from 231 patients undergoing radiotherapy for hidradenitis suppurativa in the
      last years in 2 hospitals were analyzed. The patients were treated with an
      orthovoltage therapy unit with 175 kV, 0.5 mm copper-filtering. The single doses
      reached from 0.5 Gy to 1.5 Gy up to total doses between 3.0 Gy and 8.0 Gy in one
      series. In chronic recurrent disease 2 or more series with a total dose of more
      than 10.0 Gy were given. RESULTS: Complete relief of symptoms at the end of
      radiotherapy was achieved in 89 patients (38%). In 92 patients (40%) there was
      clear improvement of symptoms. Only 2 patients did not react to radiotherapy. No
      side effects of radiotherapy occurred. CONCLUSION: Radiotherapy should be given
      more consideration as a treatment option for hidradenitis suppurativa.

PMID- 10897257
TI  - [Quality outcome of adjuvant CMF therapy in patients with breast cancer].

PMID- 10897258
TI  - [Does neoadjuvant therapy promote or delay metastasis in breast cancer?].

PMID- 10897259
TI  - [Endocrine therapy versus observation after R0 resection in node positive
      prostate cancer].

PMID- 10897260
TI  - The intensive care unit as a trauma unit.
AB  - The ICU plays a pivotal role in the care of the critically injured patient. From
      the resuscitative phase of care through the life-support phases and finally the
      recovery phase, advances in ICU care have been made in recent years. As a result,
      an improved outcome for traumatically injured patients often is seen, and the
      third peak in the trimodal distribution of trauma deaths has been affected
      significantly.

PMID- 10897261
TI  - The contemporary surgical intensive care unit. Structure, staffing, and issues.
AB  - Modern ICUs present unique challenges to physician-administrators in the current
      health care environment. Several models of care (e.g., open versus closed ICUs,
      physician extenders in the ICU) are used throughout the country, with varying
      degrees of success. Although all care models may work, the ideal model for a
      given ICU can be found only through ongoing performance improvement.

PMID- 10897262
TI  - Tertiary survey of the trauma patient in the intensive care unit.
AB  - The issues surrounding the arrival of trauma patients to the ICU have been
      defined. By necessity, many of these topics are dealt with elsewhere in greater
      detail. The basic framework within which this phase of care could be optimized
      has been provided. Pitfalls related to patients' mode of arrival to the ICU
      affect subsequent management and should direct specific clinical activity. The
      tertiary survey is a complete summation and cataloguing of a patient's injuries.
      The need for ongoing resuscitation determines how much attention can be paid to
      the tertiary survey. Clinical suspicion based on mechanism and pattern of injury
      and thorough, repeated, complete physical examination are the essential elements
      of the tertiary survey. The survey is affected by factors that alter patients'
      mental status because examination is most reliable in patients who can localize
      pain. Medications, intoxication, and head injuries are common factors that
      interfere with the reliability of the tertiary survey for variable periods.
      Radiographic assessment is used to identify injuries suspected on the basis of
      mechanism of injury, injury pattern, and findings on physical examination. Some
      studies may be done portably; others require transport within the hospital. The
      intensivist must prioritize these ongoing diagnostic studies based on patient
      stability and the need for ongoing resuscitation.

PMID- 10897263
TI  - A critical assessment of endpoints of shock resuscitation.
AB  - Modern hemodynamic therapy is not only the recognition and treatment of
      hypotension but also the avoidance and treatment of shock in its broadest sense.
      The major issues include the recognition of hypoperfusion of the body as a whole
      or its individual tissues and organ systems and the determination of the best
      endpoints for the treatment of shock. Even if all of the commonly used clinical
      indicators of shock are "normal," shock on a cellular, tissue, or organ basis may
      still be present. Whether "organ-specific" assessments, such as gastric tonometry
      or tissue oxygen tension measurement, are the ultimate answer to this problem
      remains to be seen. The determination of adequate intravascular volume (preload)
      continues to present major difficulties in the care of critically ill or injured
      patients. Although PCWP is frequently helpful, it is not a gold standard. A
      bedside ultrasonic technique, such as esophageal Doppler sonography, may replace
      the Swan-Ganz catheter technique in many patients.

PMID- 10897264
TI  - Hypothermia, coagulopathy, and acidosis.
AB  - The management of patients requiring a damage control approach taxes the
      abilities of the best equipped trauma center. These patients present with severe
      metabolic abnormalities, most notably characterized by a deadly triad of
      hypothermia, coagulopathy, and acidosis. Using volumetric, oxymetric pulmonary
      artery catheters, hypothermia and any ongoing cardiovascular abnormalities can be
      identified quickly and treatment can be monitored. External, forced air rewarming
      is a valuable technique in treating the patient with hypothermia, as are more
      invasive modalities, including body cavity lavage. Although there is no shotgun
      approach to blood component transfusion therapy, the coagulopathy shown by these
      patients has a time course that is more rapid than stat laboratories can
      presently keep up with. Given the fulminant nature of this coagulopathy, the
      authors feel justified in empirically initiating platelet and plasma or
      cryoprecipitate transfusion on identification of visible coagulopathy. The
      willingness of trauma surgeons to push the envelope in treating these most
      severely afflicted patients has allowed patients who once would have certainly
      died to lead meaningful lives.

PMID- 10897265
TI  - The early assessment and intensive care unit management of patients with severe
      traumatic brain and spinal cord injuries.
AB  - The assessment and management of neurotrauma have progressed significantly over
      the past several years. Improved understanding of the physiology of injured
      neural tissue and advances in technology have refined the approach to the care of
      patients suffering neurologic injury. Evidence-based clinical management
      guidelines, such as those developed by the Brain Trauma Foundation and the
      American Association of Neurological Surgeons, for the management of traumatic
      brain injury have been introduced to standardize certain aspects of care. The
      ongoing evolution of critical care also has had a significant impact on the care
      of patients suffering from neurotrauma. This article reviews some current issues
      related to the diagnosis and management of traumatic brain injury and spinal cord
      injury as we head into the next millennium.

PMID- 10897266
TI  - Respiratory failure. Conventional and high-tech support.
AB  - Although significant progress has been made in the treatment of patients with
      acute lung failure in the critical care setting, the mortality rate from acute
      lung injury and ARDS is unacceptably high, given the numbers of patients treated
      for these syndromes each year. The improved understanding of the pathophysiology
      of respiratory failure from basic science and clinical research is reflected in
      improved survival rates over the years. Advances in the mechanical ventilator
      (through microprocessor technology); biosurface technology; liquid ventilation;
      and, in some cases, returning to so-called "antiquated" practices of patient care
      (e.g., prone positioning) seem to have had an impact nonetheless. As refinement
      continues to occur in these areas, morbidity and mortality from lung failure will
      have a lesser impact on patients as physicians treat the consequences of organ
      failure in the ICU.

PMID- 10897267
TI  - Inflammatory responses and mediators.
AB  - The host response to injury is usually appropriate in degree and is self-limited.
      In more severe injury, the host response may persist inappropriately, leading to
      SIRS and MODS and possibly multiple organ failure. The initial response to injury
      is mediated primarily by norepinephrine, and is directed toward preservation of
      circulation to the heart and brain at the expense of other vascular beds. If
      fluid resuscitation is adequate and necrotic tissue is debrided, a hypermetabolic
      state ensues, mediated by epinephrine and directed toward supporting repair of
      injured tissue by leukocytes. Inflammatory cells are recruited to the site of
      injury and elaborate cytokines, which promote repair locally, but in severe
      injury may be systemically released and trigger remote inflammation. Cytokine
      biology presently is poorly understood, and simple anticytokine strategies have
      failed to improve survival of critically ill patients. Current therapy of SIRS
      and MODS is directed toward symptoms. Presently, it is unclear how an abnormal
      stress response arises. Cytokine spillover into the systemic circulation may
      occur. Selective transcriptional failure may be the cellular basis of organ
      dysfunction. Inappropriate production of peroxynitrite or its precursor, NO, is
      implicated in mediating cellular injury in SIRS and MODS.

PMID- 10897268
TI  - Contemporary issues with bacterial infection in the intensive care unit.
AB  - Nosocomial infection in the critically ill results from defects in the intrinsic
      barriers to microbial invasion. The diagnosis is complicated by an inability to
      perform an adequate physical examination in a patient with several compounding
      findings, usually necessitating sophisticated technologies to aid in the
      diagnosis. Pneumonia, line sepsis, urosepsis, sinusitis, endocarditis,
      peritonitis, and acalculous cholecystitis are the more common infections that
      challenge the care of the critically ill. Antibiotic therapy is adjunctive to
      efforts to preserve the barrier, but should be started early, should be targeted
      as specifically as possible to the offending organisms, and should be dosed
      adequately to ensure an effective concentration in the infected tissue.

PMID- 10897269
TI  - Monitoring organ function. Heart, liver, and kidney.
AB  - No other part of critical care evaluation is more challenging than the monitoring
      of end-organ function. Defining the endpoints of resuscitation using organ
      function is complex and controversial. Although replete with opinions and data,
      the observation of cardiac, renal, and hepatic function and the technical ability
      to categorize organ performance is crucial to providing adequate intensive care
      resuscitation and monitoring.

PMID- 10897270
TI  - Practical nutritional management in the trauma intensive care unit.
AB  - Critically injured patients offer an exceptional challenge to intensivists. Pre
      existing disease states complicate horrendous disruptions in normal anatomy and
      physiology. The hypermetabolic, catabolic response brought on by trauma, shock,
      or sepsis serves to reprioritize the normal nutritional homeostasis of the body.
      Appropriate nutritional support not only minimizes the wasting effects of
      hypermetabolism but potentially offers additional benefits. Studies of feeding
      routes, substrates, and timing suggest that adequate support may decrease
      infectious complications and modulate the metabolic response. Injured patients
      are a heterogenous group, making the definition of adequate support and
      interpretation of experimental findings difficult. Ultimately, most severely
      injured patients need directed nutritional support because of their inability to
      ingest nourishment by conventional means. This article emphasizes a practical
      approach to these patients.

PMID- 10897271
TI  - Anesthetics, sedatives, and paralytics. Understanding their use in the intensive
      care unit.
AB  - This article reviews the use of inhalational, intravenous, and epidural agents
      used in the operating room and ICU. An emphasis is placed on the rationale for
      their selection. Additionally, the side effects and expected complications are
      discussed. By developing expertise with one's own repertoire of sedatives,
      narcotics, and neuromuscular blocking agents, one may decrease postoperative
      complications and lengths of stay.

PMID- 10897272
TI  - The traveling intensive care unit patient. Road trips.
AB  - Transport of critically ill or injured patients in the hospital is a necessary
      part of ICU care. Although the overall severity of misadventures occurring during
      patient transfer is minimal, potential complications risk patient deterioration
      in settings that may not be equipped to handle cardiovascular, respiratory, or
      neurologic emergencies safely. The critical care team should provide the same
      level of monitoring and care to the transported patient outside the ICU as he or
      she receives the unit. Each hospital should have a system that meets acceptable
      standards for safe transfer of the ICU patient, which minimizes risk and
      maximizes diagnostic and treatment yield.

PMID- 10897273
TI  - The intensive care unit as an operating room.
AB  - This article is an overview of the different procedures currently performed on
      the ICU patient and emphasizes percutaneous tracheostomy and percutaneous
      gastrotomy. The steps necessary to prepare the patient, the ICU staff, and
      intensivist to achieve a safe and successful procedure are described, as are the
      indications, technique, complications, safety, and advantages to perform these
      techniques in the ICU.

PMID- 10897274
TI  - Ultrasound and other imaging technologies in the intensive care unit.
AB  - As technology advances, more imaging and procedures are performed at the bedside
      on critically ill patients in ICUs, thereby eliminating the risks of transporting
      patients. These imaging techniques can serve as diagnostic and therapeutic tools
      in treating the acute and chronic consequences of injured, critically ill
      patients. One area of growth is ultrasonography. Critical care applications of
      ultrasonography are expanding, and the learning curve of surgeons and
      intensivists performing some of these studies is improving. Ultrasonography can
      supplement physical examination and provide useful "real-time" information on
      nearly every body cavity. Other imaging technology is also available in a
      portable form, enabling imaging directly at the bedside. Images are now becoming
      readily and easily available with the advancement of teleradiology. Some of the
      imaging modalities are still in development, and their clinical effectiveness is
      being studied. In the future, more uses of these various imaging technologies may
      become evident and cost-effective.

PMID- 10897275
TI  - The injured elderly in the trauma intensive care unit.
AB  - The injured elderly patient in the ICU presents many challenges. Demographic
      changes in western society will dramatically increase the patient population in
      question, and new, older, subsets are growing. The association of severe injury,
      preinjury comorbidity, and the aging process narrows the ability of the patient
      to respond to the stress of injury. When compared with younger patients, the
      elderly have greater mortality, morbidity, and higher costs. Age alone, however,
      does not predict outcome. Although aggressive or maximally supportive care is
      advocated, controlled data supporting this approach are lacking. Significant
      economic, sociologic, and ethical issues confront the care providers in almost
      every case. Continued and heightened study of all aspects of our injured elders
      focusing on the determinants of outcome is required. A realistic appraisal of the
      limitations of care and a reassessment of the financial implications of providing
      extended care are critical to the continuing ability to respond to this growing
      need.

PMID- 10897276
TI  - Issues in potential organ donor management.
AB  - The shortage of organ donors has become a serious problem in modern medicine.
      Room for improvement exists in our ability to convert potential donors to actual
      donors based on the available numbers and a significant amount of recent
      research. A significant percentage of the potential donors represent head-injured
      patients, so a significant amount of responsibility falls on surgeons to optimize
      the opportunity for donation. There are clear steps along the pathway from
      potential to actual donor where physicians can have a significant effect on the
      rate of successful donation: 1. Identify all potential donors and institute a
      review system to verify that all potential donors are being identified in your
      area. 2. Establish an acceptable method to rapidly and accurately determine brain
      death in potential donors using the local available services. 3. Approach all
      potential donor families for consent, decouple death notification and consent
      request, use a member of the hospital team and an OPO representative to approach
      the family, and make the request in a private setting. 4. Use an aggressive,
      proactive approach to the medical management of the potential donor using the
      techniques described to limit the number of medical failures and maximize the
      number of organs donated per donor. Institute a review process to evaluate any
      medical failures that occur. Given the difference between the numbers of
      potential versus actual donors, the authors' significant contact with potential
      donors, and the clear opportunities for improvement in their approach, the
      surgical community must address these issues surrounding the optimal management
      of potential donors and their families.

PMID- 10897277
TI  - Substance abuse and withdrawal in the intensive care unit. Contemporary issues.
AB  - Because 36% of intentional injury victims are drug dependent, the association
      between drug abuse and violence, especially in urban settings, is high.
      Withdrawal syndromes in ICU patients confuse their clinical management, may be
      extremely difficult to diagnose, are often lethal, need to be suspected, and
      should be prophylaxed against; therefore, all ICU patients should be considered
      to be at high risk for drug or alcohol dependence, should be tested for evidence
      of such drugs, and should be interviewed (together with their family members) for
      the presence of drug dependence traits. Appropriate patients should be referred
      for formal evaluation and treatment. Withdrawal syndromes must be promptly
      recognized, differentiated from traumatic or metabolic deterioration, and
      immediately treated. As patients are unique, so is their drug dependence.
      Individualized withdrawal therapy, not a "one method fits all" approach, works
      best. The mainstay of most withdrawal therapy is supportive care and
      benzodiazepine therapy. Also, considering the high rate of multiple intoxicants
      present in trauma patients, withdrawal can occur from multiple agents in a single
      patient, further compounding these difficulties. Withdrawal from unusual
      substances, such as GHB, or from therapeutic interventions (e.g., prolonged
      opioid or benzodiazepine administration) also must be considered.

PMID- 10897278
TI  - Termination of life support after major trauma.
AB  - As the population continues to age, greater numbers and more severely injured
      elderly patients require care in ICUs. With the attendant increase in the medical
      complexity of such patients, investigators anticipate that trauma and critical
      care resources will become increasingly stretched. Because of economic and
      societal forces, it will become increasingly important for trauma surgeons to
      appropriately counsel patients and their families regarding the outcome from
      their injuries and to become comfortable approaching families about withdrawal of
      support when medical futility is recognized. The authors propose the following
      guidelines for discussing limitation or termination of life support with patients
      and their families. Physicians should (1) discuss the patient's wishes regarding
      life support on admission or early in the hospital course; (2) at the initial
      discussion, establish who the decision maker will be if the patient is or becomes
      incapacitated; (3) maintain regular communication and continuity of care; and (4)
      inevitably, when conflict occurs, involve consultants and a hospital ethics
      committee for assistance in its resolution.

PMID- 10897279
TI  - Billing, coding, and documentation in the critical care environment.
AB  - Optimal conduct of modern-day physician practices involves a thorough
      understanding and application of the principles of documentation, coding, and
      billing. Physicians' role in these activities can no longer be secondary.
      Surgeons practicing critical care must be well versed in these concepts and their
      effective application to ensure that they are competitive in an increasingly
      difficult and demanding environment. Health care policies and regulations
      continue to evolve, mandating constant education of practicing physicians and
      their staffs and surgical residents who also will have to function in this
      environment. Close, collaborative relationships between physicians and
      individuals well versed in the concepts of documentation, coding, and billing are
      indispensable. Similarly, ongoing educational and review processes (whether
      internal or consultative from outside sources) not only can decrease the
      possibility of unfavorable outcomes from audit but also will likely enhance
      practice efficiency and cash flow. A financially viable practice is certainly a
      prerequisite for a surgical critical care practice to achieve its primary goal of
      excellence in patient care.

PMID- 10897280
TI  - Foreword: concepts of minimally invasive plate osteosynthesis.

PMID- 10897281
TI  - The evolution of modern plate osteosynthesis.
AB  - Plate osteosynthesis is still recognized as the treatment of choice for most
      articular fractures, many metaphyseal fractures, and certain diaphyseal fractures
      such as in the forearm. Since the 1960s, both the techniques and implants used
      for internal fixation with plates have evolved to provide for improved healing.
      Most recently, plating methods have focused on the principles of 'biological
      fixation'. These methods attempt to preserve the blood supply to improve the rate
      of fracture healing, decrease the need for bone grafting, and decrease the
      incidence of infection and re-fracture. The purpose of this article is to provide
      a brief overview of the history of plate osteosynthesis as it relates to the
      development of the latest minimally invasive surgical techniques.

PMID- 10897282
TI  - Minimally invasive plate osteosynthesis and vascularity: preliminary results of a
      cadaver injection study.
AB  - A cadaver arterial injection study was performed to analyse the vascular supply
      to the femur and to study the effects of two surgical plating techniques on
      femoral vascularity. A 16-hole LC-DCP was applied on the intact femora of five
      fresh human cadavers. On one side, the plate was inserted using a conventional
      lateral plate osteosynthesis (CLPO) technique with elevation of the vastus
      lateralis muscle to expose the shaft. On the contralateral side, the plate was
      inserted percutaneously beneath the muscle using a minimally invasive plate
      osteosynthesis (MIPO) technique. After plating, blue silicone dye was injected
      through the common femoral artery. Cadaveric dissection was then performed to
      identify the femoral perforating arteries (PAs) and the nutrient artery (NA) of
      the femur. The pattern of periosteal filling and medullary perfusion of the
      injected dye was analysed and the topography of the PAs and NA was determined.
      CLPO placed the PAs and NA of the femur at risk. MIPO maintained the integrity of
      the PAs and NA and was associated with superior periosteal and medullary
      perfusion. The results of this study indicate that MIPO is superior to the CLPO
      in maintaining arterial femoral vascularity and perfusion.

PMID- 10897283
TI  - Minimally invasive plate fixation in femoral shaft fractures.
AB  - Bridge-plating with its advantages in terms of vascularity and bone healing is a
      well established procedure today in the treatment of comminuted femoral
      fractures. Bridge-plating means that the fracture site is not interfered with
      during the operative procedure. This paper introduces a surgical technique in
      which the plate is inserted through isolated proximal and distal incisions only,
      behind the vastus lateralis. Alignment is secured by the plates, the fracture
      site remains untouched, fixation and screw insertion is restricted to the
      proximal and distal main fragments. Longitudinal femoral fractures extending
      right into the trochanteric and or condylar areas are the main indication for
      minimally invasive plate fixations with angled blade plates or condylar screws
      since fractures which are restricted to the diaphyseal area are mostly treated by
      nailing today. The surgical trauma resulting from plating by proximal and distal
      incisions only is less than that associated with conventional techniques.
      Indirect reduction of femoral fragments is much easier since the integrity of the
      surrounding muscles and soft tissue is preserved, the fragments often being
      reduced simply by traction. Adjustment of rotation is an essential aspect
      requiring careful attention. For special indications, namely comminuted fractures
      affecting a large part of the femur and extending into the trochanteric or
      condylar areas, insertion of the plate via proximal and distal incisions only is
      a further development in bridge-plating which minimizes surgical trauma and
      operation time.

PMID- 10897284
TI  - Minimally invasive percutaneous plate osteosynthesis (MIPPO) using the DCS in
      proximal and distal femoral fractures.
AB  - In a prospective study, 14 cases of supracondylar or subtrochanteric fractures or
      osteotomies were stabilized with a dynamic condylar screw (DCS) inserted using a
      minimally invasive percutaneous plate osteosynthesis (MIPPO) technique. The
      technique consisted of 4 major steps: 1) placement of the guide wire under
      fluoroscopic control and condylar screw insertion through a stab incision; 2)
      plate insertion beneath the vastus lateral muscle; 3) engagement of the condylar
      screw to the plate using a modified T-handle and, 4) plate fixation to the shaft
      using percutaneously inserted self-cutting screws. Between October 1994 and
      December 1995, 14 cases in 12 patients met the inclusion criteria. There were 11
      acute fractures (6 subtrochanteric, 5 supracondylar) and 3 corrective
      osteotomies. Nine fractures were closed, and 2 were open. One 97-year-old patient
      died 6 weeks after trauma. There were no infections and 12 of 13 cases healed
      without a second procedure. There was 1 implant failure (plate screw breakage),
      which required repeat fracture fixation. At follow-up, there were 2 varus
      deformities above 5 degrees, 2 shortenings over 20 mm, and 1 rotational deformity
      of 20 degrees. According to the Neer score, there were 6 excellent, 1
      satisfactory, 3 unsatisfactory results and no failures. The results of this
      technique compare favourably with those of other series of osteosynthesis of
      subtrochanteric or supracondylar femoral fractures treated with internal fixation
      without the added morbidity associated with an extensive approach or autogenous
      bone grafting. However, the surgical technique is demanding, and care must be
      taken to restore the axial alignment.

PMID- 10897285
TI  - Transarticular joint reconstruction and indirect plate osteosynthesis for complex
      distal supracondylar femoral fractures.
AB  - In a prospective study conducted between 1992 and 1995, displaced Muller type C2
      C3 intraarticular fractures of the distal femur were treated using an indirect
      plate fixation technique and a lateral parapatellar arthrotomy for the direct
      reduction of the condylar block. There were 6 closed, and 2 open fractures (1
      grade II and 1 grade IIIB). Following reconstruction of the articular block, the
      block was indirectly reduced and fixed to the shaft by a plate inserted by the
      retrograde method beneath the vastus lateralis. Transcutaneous/transmuscular
      screws were used to fix the plate to the shaft. Time to bone healing was 12 weeks
      (median range 8-17 weeks) after surgery without needing primary or secondary bone
      grafts. There were no infections or refractures. Except for one case which
      required a corrective osteotomy for 10 degrees of varus malalignment, there were
      no revisions. According to the Neer score, there were 6 excellent or satisfactory
      results, 2 unsatisfactory results, and no failures. At follow-up, there were 2
      varus-valgus deformities greater than 5 degrees, 2 leg length discrepancies
      greater than 10 mm, and 2 rotational deformities of 15 degrees. The treatment
      results for complex supracondylar/intracondylar fractures of the distal femur
      obtained with this technique compare favourably with other reported series using
      different techniques without the added morbidity associated with autogenous bone
      grafting. However, the surgical technique is demanding and special care must be
      taken to ensure correct axial alignment.

PMID- 10897286
TI  - Minimally invasive plate osteosynthesis of distal fractures of the tibia.
AB  - Minimally invasive plate osteosynthesis of distal tibial fractures is technically
      feasible and may be advantageous in that it minimizes soft tissue compromise and
      devascularization of the fracture fragments. The technique involves open
      reduction and internal fixation of the associated fibular fracture when present,
      followed by temporary external fixation of the tibia until swelling has resolved.
      Subsequent limited, but open reduction and internal fixation of the articular
      fragments when displaced followed by minimally invasive plate osteosynthesis of
      the tibia utilizing precontoured tubular plates and percutaneously placed
      cortical screws is performed. The semitubular plate was chosen because it adapts
      more easily to the bone contours than the stiffer small fragment LC-DCP does.
      Twenty patients (age 25-59 years) with unstable intraarticular or open
      extraarticular fractures have been treated including 12 A-type, 1 B-type and 7 C
      type fractures according to the AO classification. Two fractures were open (both
      Gustilo Type I). Closed soft tissue injury was graded according to Tscherne with
      3 type C0, 7 type C1, 7 type C2 and 1 type C3. All fractures healed without the
      need for a second operation. Time to full weight-bearing averaged 10.7 weeks
      (range 8-16 weeks). Two fractures healed with > 5 degrees varus alignment and 2
      fractures healed with > 10 degrees recurvatum. No patient had a deep infection.
      The average range of motion in the ankle for dorsiflexion was 14 degrees (range 0
      30 degrees) and plantar flexion averaged 42 degrees (range 20-50 degrees). With
      longer follow-up and a larger number of patients, the authors feel confident that
      the minimally invasive technique for plate osteosynthesis for the treatment of
      distal tibial fractures will prove to be a feasible and worthwhile method of
      stabilization while avoiding the severe complications associated with the more
      standard methods of internal or external fixation of those fractures.

PMID- 10897287
TI  - Beyond black, white and Hispanic: race, ethnic origin and drinking patterns in
      the United States.
AB  - This study used data on 42,862 U.S. adults, including 18,352 past-year drinkers,
      to describe differentials by race and national origin in U.S. drinking patterns.
      Age-sex standardized estimates were presented within 21 categories of ethnic
      origin for whites and within five categories each for individuals of black and
      other races. Of the three racial groups, whites were the most likely to drink,
      but blacks had the highest volume of intake and frequency of heavy drinking.
      Differences by ethnic origin within racial categories were as marked as
      differentials between races. Compared to whites of European origin, those of
      Hispanic and native American origin were less likely to drink but consumed more
      alcohol on days when they drank. Whites of Southern and Eastern European origin
      drank proportionately more wine and demonstrated more moderate drinking patterns
      (lower intake per drinking day and/or less frequent heavy drinking) than those of
      Northern or Central European origin. Hispanics of Caribbean origin were less
      prone to heavy drinking than other white Hispanics; similarly, blacks from the
      English-speaking Caribbean showed more moderate drinking patterns than other
      blacks. Individuals of Asian origin, in particular those of non-Japanese origin,
      had the most moderate drinking patterns within the category of other race.
      Although the black/white differentials in volume of intake and frequency of heavy
      drinking disappeared after adjusting for marital status, education and income,
      most of the differences by ethnic origin retained their statistical significance
      if not their original magnitudes. These findings indicate that cultural forces
      exert a strong effect on drinking behavior. Differences among European whites
      with respect to prevalence of drinking, beverage preference and frequency of
      heavy drinking suggest that the association between ethnic origin and drinking
      behavior may persist even after many generations of presumed acculturation.

PMID- 10897288
TI  - The drinking of earlier and more recent Russian immigrants to Israel: comparison
      to other Israelis.
AB  - OBJECTIVES: Russia has a high level of per capita alcohol consumption, while the
      level in Israel is low. Since 1989, over 820,000 Russian Jews immigrated to
      Israel. In the 1970's and early 1980's, a smaller wave of immigration from Russia
      to Israel occurred (approximately 170,000). The drinking of earlier immigrants
      was compared to recent immigrants and other Israelis. METHODS: Data came from a
      1995 national survey of Israeli household residents. Of 4984 Israeli respondents,
      292 were Russian immigrants who arrived since 1989 and 131 were Russians who
      immigrated earlier. Groups were compared with logistic regression. RESULTS:
      Recent Russian immigrants were more likely to drink in the last 12 months, to
      drink frequently and to get drunk than other Israelis. The earlier Russian
      immigrants were not more likely than other Israelis to report drinking in the
      last 12 months or frequent drinking, but were more likely to report 30-day
      drinking and getting drunk. In direct comparison of recent and earlier Russians,
      recent immigrants reported more frequent drinking than earlier immigrants.
      CONCLUSIONS: The results for drinking and frequency of drinking are consistent
      with acculturation effects as well as other explanations. Further investigation
      in studies with appropriate designs will be necessary to clarify the meaning of
      these results.

PMID- 10897289
TI  - Implications of privatizing/deregulating alcohol retail sales: projections of
      alcohol consumption in Ontario.
AB  - PURPOSE: To project the consequences of privatizing or deregulating current
      alcohol retail monopolies in Ontario, Canada. METHODS: The projection is based on
      a multiplicative model and applied to estimate per capita alcohol consumption for
      four hypothetical scenarios, including both partial and complete privatization
      for the Province of Ontario, Canada. Those scenarios are mainly focused on the
      two dimensions of changes affected by privatization: alcohol physical
      availability and economic availability (i.e., retail prices). Various assumptions
      involving availability and prices are largely based on the Canadian and
      international research literature on deregulation/privatization. RESULTS AND
      IMPLICATIONS: The study showed that per capita alcohol consumption in the
      short/medium term is expected to increase in all four hypothetical scenarios
      examined, with the magnitude ranging from 11% to 27%. The sensitivity analysis
      also revealed a similar increase in alcohol consumption, even though the
      magnitude of the increase would be less for some scenarios. Therefore, any
      deliberations on modifying alcohol control policies are well advised to proceed
      with caution, since an increase in alcohol consumption is likely to be associated
      with elevated levels of drinking-related problems.

PMID- 10897290
TI  - Factors associated with the initiation of smoking by Kuwaiti males.
AB  - PURPOSE: To estimate the age patterns in cumulative probability of smoking
      initiation among Kuwaiti adult males and to study the differentials in smoking
      initiation in relation to factors such as age-cohort, marital status, educational
      level, income, type of residence, and history of smoking among family members and
      friends. METHODS: A stratified three stage cluster sampling design was
      implemented for the selection of the sample. A self-administered questionnaire
      was completed by 1798 Kuwaiti adult males working in different ministries.
      RESULTS AND IMPLICATIONS: Of the 1798 respondents, 34.4% were classified as
      current smokers, 17.7% as former smokers and 47.9% as non-smokers. The highest
      probability of smoking initiation (among current and former smokers) was found
      for the age group 15-20 years, where almost 29% of the respondents initiated
      smoking. In the univariate analysis, marital status, education, income, type of
      residence, and history of smoking among family members and friends showed
      significant variation in the age-patterns of initiation. In the Cox proportional
      hazard regression model, education, type of residence, and history of smoking
      among family members and friends were found to be independently associated with
      the risk of initiation. The highest risk of initiation (Relative Risk (RR) =
      1.85; 95% CI: 1.62-2.10) was found among those who had a history of smoking in
      family and friends. Individuals in the lowest education category (RR = 1.64; 95%
      CI: 1.32-2.04) and those residing in apartments (RR = 1.65; 95% CI: 1.43-1.92)
      were at a higher risk of initiation compared with those who had university
      education or those who resided in villas. The results of the study should prompt
      further efforts to develop tobacco control policies in Kuwait and the other
      Arabian Gulf countries to help establish norms for not initiating smoking through
      persistent messages to not start or to stop smoking. There is also a need to
      enhance awareness about the influence of smokers in family or friends on other
      people to initiate smoking.

PMID- 10897291
TI  - Social class, drinking and alcohol-related mortality.
AB  - The main purpose of this study is to investigate the magnitude of class
      differences in the distribution of alcohol consumption in Sweden, and to assess
      whether this is compatible with the observed pattern in class-specific mortality.
      The emphasis is put on analyses of survey data from 1990, but we also provide an
      overview of earlier published data. The findings suggest that, over the past 20
      30 years, there has been an equalization, or even reversal, between social strata
      in the average consumption of alcohol, such that the consumption level for manual
      laborers is now at parity with, or possibly exceeds, the level for non-manual
      employees. This shift may also have been accompanied by a shift in the
      dispersion: the 1990 survey data indicate that the consumption distribution for
      the manual laborers is more skewed than that for the non-manual employees, while
      no such tendency was detected in the early data. Calculations demonstrated that
      this difference in dispersion may well account for the elevated rate of alcohol
      related mortality among manual laborers. The results are finally discussed as a
      case of deviation from the general rule of collective change in consumption.

PMID- 10897292
TI  - Smoking initiation and cessation in Norway and the United States: a comparison of
      two cross-sectional surveys.
AB  - PURPOSE: Smoking prevalence in a population is affected by the proportion of
      adolescents who start to smoke, and the proportion of smokers who quit. Smoking
      prevalence has declined linearly in the US and in the state of California during
      the last 2 decades. Due to an increase in female smoking, the Norwegian smoking
      prevalence has been stable at around 35% since 1980, while other European
      countries have seen reductions of at least 10 percentage points. METHODS: We
      compared data from two cross-sectional studies; one from Western and Central
      Norway (n = 5014), and one from Northern California (Stanford Five-City Project)
      (n = 2189). RESULTS: Norwegian smoking prevalence figures were significantly
      higher in all age-sex groups younger than 60 years. The proportion of former
      smokers was not different, suggesting that the differences between the samples
      are due to higher smoking initiation in Norway. University education was the most
      potent covariate of both ever-smoking and current smoking across samples and
      gender. Amount of physical exercise was associated with never-smoking in Norway,
      but not in the US. Having smoking parents was related to ever-smoking in women
      but not in men in both samples. Smoking parents also was related to current
      smoking in Norway but not in the US. IMPLICATIONS: Norway should increase efforts
      to prevent smoking initiation among adolescents, and especially among girls.

PMID- 10897293
TI  - Cutting film violence: effects on perceptions, enjoyment, and arousal.
AB  - The authors investigated the effects of cutting specific graphic scenes of film
      violence on self-reports of arousal, enjoyability, and perceptions of violence
      among a sample of U.S. students. In 3 studies, they varied film exposure from 1
      1/2 min in the 1st study to a complete motion picture (American vs. British
      version of same film) in the 3rd. In all 3 studies, the participants rated the
      cut versions as less violent than the uncut versions. The participants
      distinguished quite subtle differences in levels of violence, even when the cuts
      were minor and contextualized within an entire movie. Cutting the movie
      significantly increased its enjoyability for the women; for the men, there was no
      significant difference. Cutting violent films made no difference in arousal for
      the men but substantially lowered self-report levels of arousal for the women.

PMID- 10897295
TI  - Assumptive world of traumatized South African adults.
AB  - One way of understanding the impact of traumatic events is through exploration of
      cognitive changes that confront a traumatized individual. The author investigated
      changes in individuals' basic assumptions after traumatic experiences. The
      participants were 65 people who had been traumatized by representatives of the
      South African apartheid government. From the total sample, 36 participants had
      witnessed the violent death of a close relative (sibling, mother, or father). The
      remaining 29 had been tortured and detained. The author administered the World
      Assumption Scale (R. Janoff-Bulman, 1989), a semistructured questionnaire on
      basic assumptions developed for the present study, and the Post-Traumatic Stress
      Disorder Clinical Checklist (American Psychiatric Association, 1994). Traumatic
      events affected the participants' basic assumptions about the meaning and
      benevolence of the world. The tortured and detained group and the bereaved group
      showed differences in their assumptions of self-worth following the trauma.
      Cognitive approaches can yield invaluable therapeutic insights into strategies
      for coping with trauma.

PMID- 10897296
TI  - Coping with failure: relationship with self-concept discrepancy and attributional
      style.
AB  - In the relationship of attributional style and self-concept discrepancy with
      coping behavior among 10th-grade Hong Kong Chinese students, 3 significant
      canonical variate pairs were identified. The total criterion redundancy showed
      that self-concept discrepancy and attributional style predicted about 20% of the
      variance of coping behavior. The 1st variate pair indicated that students with
      small self-concept discrepancy and low-depressive attributional style tended to
      cope with failure by planful problem solving and by positive reappraisal. The 2nd
      variate pair showed that students, particularly girls, with small self-concept
      discrepancy in verbal ability and same-sex peer relations tended to cope with
      failure by seeking social support. The last variate pair showed that students
      with great self-concept discrepancy in same-sex peer relations and parent
      relations tended to cope with failure by avoiding or escaping. The 3 canonical
      variate pairs also suggested a new taxonomy for coping behavior: mobilization of
      internal coping resources, mobilization of external coping resources, and the
      inability to mobilize any coping resources.

PMID- 10897294
TI  - Attributions of deviance to self and peers by Japanese and U.S. students.
AB  - The author examined self-enhancement bias among 5th and 11th graders in the
      United States and Japan. After listening to stories describing aggressive,
      depressive, oppositional, and school-phobic behaviors of hypothetical peers, the
      participants rated the likelihood that they themselves and other students their
      age would act like the story protagonists. The U.S. students generally showed no
      greater self-enhancement tendencies than did the Japanese students; in addition,
      the relationships between positive and negative self-concepts and ratings of self
      similarity to deviant exemplars were similar in both samples. In the depressed
      and oppositional stories, the 11th graders rated themselves less like the deviant
      characters and more different from their peers than did the 5th graders.

PMID- 10897297
TI  - Covert self-reinforcers, fear of consequences, and health behavior.
AB  - A sample of 125 U.S. college students reported how frequently they exercised
      vigorously; wore seat belts in automobiles; and avoided consumption of red meat
      and foods high in dietary cholesterol, saturated fat, and salt. They also
      reported their fears of long-term negative effects from the unhealthful
      alternatives and both the frequencies and intensities of 6 self-administered
      covert consequences: 3 positive for healthful behaviors and 3 negative for the
      unhealthful alternatives. Diet-related health behaviors were best predicated by a
      single scale composed of all 12 covert-consequence items. Factor analyses
      suggested the use of 2 scales for exercise and use of seat belts: 1 rating
      positive consequences and the other rating negative consequences. For both
      behaviors, only the positive-item scale predicted in multiple regression. Fear
      was correlated with all health behaviors except exercise, but it contributed
      independently only to red-meat avoidance.

PMID- 10897298
TI  - [Manifestations of histoplasmosis].
AB  - Two patients, a 34-year old man-to-woman transsexual and a 32-year-old man, with
      aids presented with pulmonary symptoms, fever, serious weight loss and an oral
      ulcer. A third patient, a 16-year-old boy, had signs of transverse myelitis and
      meningitis without immunodeficiency. All were South American citizens and had
      disseminated histoplasmosis. After antifungal treatment they recovered, although
      the third patient remained a wheelchair user. If pulmonary or miliary
      tuberculosis is suspected in a patient originating from South America,
      histoplasmosis should be considered. Oral ulcers and skin lesions can be
      diagnostic clues. Specific stainings of direct preparations and longer-lasting
      cultures of various materials, especially of biopsy samples, then provide the
      diagnosis.

PMID- 10897299
TI  - [Timing of administration of sulfonyl urea derivatives].
AB  - In daily practice the optimal time of administration of sulphonylurea derivatives
      is not always clear. Administration 30 minutes prior to meals allegedly offers
      the advantage that an active plasma level has been reached when food enters the
      gastrointestinal tract. Alleged disadvantages are higher risk of hypoglycaemia
      and poor compliance. In publications from Medline 1966-1999 the 24-hour
      availability of sulphonylurea derivates was the same after administration at
      different times. The absorption rate of glibenclamide and tolbutamide was not
      affected by food. Study results concerning gliclazide were contradictory. The
      absorption rate of glipizide was reduced after ingestion during breakfast. In
      several, partly the same, small studies the findings concerning the variation of
      the glucose level in time in patients with type 2 diabetes mellitus were
      equivocal. The pharmacokinetic and pharmacodynamic evidence that sulphonylurea
      derivatives should be taken 30 minutes before meals appears to be so limited that
      in our opinion it is out-weighed by the potential risk that this advice may
      compromise the drug compliance of users.

PMID- 10897300
TI  - [Practice of systematic reviews. VI. Searching, selection and methodological
      evaluation of etiological research].
AB  - Optimal search strategies for the identification of publications on aetiological
      research are currently not available. The definition of adequate selection
      criteria is necessary to limit the harvest to a relevant and homogeneous set of
      publications. Yet, the harvest should be high in order to prevent many relevant
      papers being missed. The methodological assessment of aetiological research
      should be aimed at the estimation of the presence of selection bias, information
      bias, and confounding. Important items of the methodological assessment are
      independent and standardised assessment of exposure and outcome, high response
      rate, no selective dropout, and adjustment for confounding in the analysis.

PMID- 10897301
TI  - [Immunology in the medical practice. XXVII. Mannose-binding lectin, an important
      link for nonspecific or hereditary immune reaction].
AB  - In the course of the past two decennia, a 3rd route of complement activation
      (next to the classical and the alternative routes) has been identified: the
      lectin route in which mannose-binding lectin (MBL) plays an essential role. MBL
      is produced in the liver. From the phylogenetic and functional points of view,
      complement activation via MBL falls in between the alternative and the classical
      routes and combines the advantages of the former (an early response, without the
      intervention of antibodies) with those of the latter (high specificity). The
      binding of MBL to the surface of a microorganism results in the activation of two
      serine proteases (MASP1 and MASP2) that are coupled to MBL. These enzymes can
      activate C4 and C2 so that, via the MBL route, the C3-convertase of the classical
      route (C4b2b) is produced long before there are any specific antibodies. The gene
      for MBL is located on the long arm of chromosome 10 and consists of a promoter
      gene and 4 exons coding for the protein. The prevalence of mutations in the MBL
      gene is about 10%, but in Africa South of the Sahara it is as high as 30%. MBL
      deficiency predisposes both children and adults to all sorts of infectious
      diseases, chronic diarrhoea, tonsillitis, otitis media, pneumonia,
      (meningococcal) meningitis, sepsis and osteomyelitis. Remarkably, MBL deficiency
      may actually be advantageous in some infections, because certain microorganisms
      use MBL or complement to invade the cell.

PMID- 10897302
TI  - [Diagnosis and treatment of non-Hodgkin lymphoma in Netherlands: variation in
      guidelines and in practice].
AB  - OBJECTIVE: To investigate current guidelines for diagnosis and treatment of
      intermediate or high grade non-Hodgkin's lymphoma (NHL), stage I-IV (Burkitt's
      and lymphoblastic lymphoma excluded) and to compare this with current clinical
      practice. DESIGN: Descriptive. METHOD: An inventory of guidelines for diagnosis
      and treatment of NHL of the Regional Cancer Centres (RCCs) was made in mid-1998,
      an enquiry containing questions about the practical situation concerning the
      diagnosis and treatment of NHL patients was sent to 59 internists-haematologists
      in non-university hospitals of the RCC regions Amsterdam, Rotterdam and South.
      RESULTS: Apart from the standard diagnostics, the RCCs recommended several
      examinations for staging. For the initial staging the haematologists not always
      requested the recommended CTs of chest and abdomen and most of them did no
      restaging after the last course of chemotherapy. Half of them left the assessment
      of lymph node biopsy samples to a lymphoma panel. The recommended primary
      treatment consisted mainly of chemotherapy with cyclophosphamide-doxorubicin
      vincristine-prednisone (CHOP). In certain regions, the schedule was slightly
      changed, with additional tenoposide and bleomycin (CHVmP/BV). The treatment
      schedules were heterogeneous, especially for stage I NHL. In leukopenia and/or
      thrombocytopenia, postponement was recommended, but dosage reduction was carried
      out immediately, especially in older patients, sometimes with administration of a
      haemopoietic growth factor. Recurrence NHL was treated in accordance with the
      guidelines with second-line chemotherapy, if possible followed by peripheral stem
      cell transplantation in a haematooncological centre. CONCLUSION: Considering
      these results development of national guidelines for NHL would seem to be
      desirable.

PMID- 10897303
TI  - [Fatal anaphylactic reaction after oral acetazolamide (diamox) for glaucoma].
AB  - A woman aged 66 was prescribed acetazolamide (Diamox) in the outpatient clinic
      because of glaucoma. She went into irreversible anaphylactic shock with massive
      pulmonary oedema, probably due to a cross reaction in sulphonamide allergy.
      Before prescribing acetazolamide, the physician should inquire about sulphonamide
      allergy because of the related chemical structure of the substances. Such an
      allergy should be regarded as a contraindication.

PMID- 10897304
TI  - [Serum lactate levels as an indicator of tissue hypoxia in severely ill
      patients].

PMID- 10897305
TI  - [Proctocolectomy with ileum 'pouch'-anal anastomosis: results from 100
      consecutive patients in the Academic Medical Center in Amsterdam, 1994-1999].

PMID- 10897306
TI  - [2nd International Meeting on Hypertension and the Kidney. Madrid, Spain, 3-5
      February 2000. Abstracts].

PMID- 10897307
TI  - Leukemia. There are reasons for hope.

PMID- 10897308
TI  - Health tips. Understanding your T-score.

PMID- 10897310
TI  - Walking cuts heart attack risk.

PMID- 10897309
TI  - New influenza drug offers some help.

PMID- 10897311
TI  - Hypertension drugs. They can treat more than high blood pressure.

PMID- 10897313
TI  - Staying connected. Close ties promote health.

PMID- 10897312
TI  - Prostatitis. A common, often vexing problem.

PMID- 10897314
TI  - I've heard about tear duct plugs to manage dry eyes. Are these safe?

PMID- 10897315
TI  - Do I need to see a doctor to get a prescription for Viagra? I've seen ads
      offering Viagra direct by mail.

PMID- 10897316
TI  - 24th Annual meeting of the German Society for Cell Biology. Karlsruhe, March 26
      30, 2000. Abstracts.

PMID- 10897317
TI  - 4th Congress of the European Federation of Neurological Societies. Lisbon,
      Portugal, September 7-11, 1999. Abstracts.

PMID- 10897318
TI  - 2nd International Meeting on Inflammatory Bowel Diseases. Capri, Italy, June 18
      21, 2000. Abstracts.

PMID- 10897319
TI  - Epidemiology and classification of urinary incontinence.
AB  - Urinary incontinence is a common symptom affecting the physical, psychological,
      social and economic well-being of individuals and their families. It also poses a
      considerable economic burden on health and social services. The literature
      reports widely varying prevalence rates for incontinence that are partially
      explained by methodological differences between studies. However, community-based
      studies indicate that approximately 6% of the population, particularly women and
      older people, will have urinary incontinence of sufficient severity to interfere
      with their quality of life. This represents a significant demand for health care.
      Although further research on prevalence is unlikely to add anything new to
      current knowledge on the size of the problem, more information is needed on the
      onset, progression and risk factors of urinary incontinence to inform methods of
      effective treatment and preventive strategies. In addition, there has been little
      investigation of the triggers to seeking professional help or of the response of
      health professionals to patients' demands for treatment, either for incontinence
      or other lower urinary tract symptoms. The aetiology of incontinence is
      multifactorial; incontinence is caused by pathophysiological impairments to the
      lower urinary tract and neurological system, as well as a range of external
      factors. The key to effective management, therefore, is a comprehensive
      assessment of the patient, including other lower urinary tract symptoms, so that
      appropriate intervention is tailored on a diagnosis and not on symptoms.

PMID- 10897320
TI  - Urinary incontinence: anatomy, physiology and pathophysiology.
AB  - Urinary continence in the female depends on urine being stored in a receptive
      bladder closed by a competent sphincter mechanism. Incontinence can result from a
      failure of storage, i.e. detrusor instability or a failure of the sphincter
      mechanism leading to stress incontinence. In addition there is a complex neural
      control which co-ordinates urethral and bladder function to alter from storage to
      voiding at socially acceptable times. Although the majority achieve continence
      early in childhood, there are a number of insults brought to bear on the
      continence mechanism other than advancing age. The most notable of these is
      childbirth with resultant neuromuscular damage to the pelvic floor. The onset of
      the menopause with oestrogen deprivation and increased risk of urinary tract
      infection can further compromise bladder function. Restoration of continence in
      those affected involves a thorough knowledge of normal functioning anatomy and
      physiology of the lower urinary tract as only through improved understanding of
      disease mechanisms can rational treatment be applied.

PMID- 10897321
TI  - Assessment and investigations for urinary incontinence.
AB  - Assessment of a woman complaining of urinary incontinence includes full
      urological, gynaecological, medical, surgical and drug histories. General,
      neurological, abdominal and pelvic examinations are undertaken and with the
      history, enable a presumptive diagnosis to be formulated. Investigations for
      incontinence should be selected to suit the individual woman's need. Non
      specialist investigations include urine testing, completion of a urinary diary
      and symptom score, pad testing, measurement of residual urine volume and
      biochemical tests. Specialist investigations include uroflowmetry, conventional
      and ambulatory cystometry, urethral pressure profilometry and measurement of
      urethral electrical conductance and leak point pressure. Imaging using
      ultrasound, X-ray, magnetic resonance or isotopes is sometimes indicated. While
      neurophysiological testing has little clinical application, cystourethroscopy is
      of value in various subgroups of women. Thorough assessment and appropriate
      investigation together result in an accurate diagnosis which in turn allows
      appropriate treatment for urinary incontinence to be initiated.

PMID- 10897322
TI  - Conservative management for urinary incontinence.
AB  - Gynaecologists have become increasingly aware of the need to offer conservative
      therapy for genuine stress incontinence. There is good objective evidence from
      randomized controlled trials to support the use of supervised pelvic floor
      exercises. The efficacy of biofeedback therapy, vaginal cone weights and
      electrostimulation therapy is variable and requires further study to identify
      those women who will benefit the most. The mainstay of therapy for detrusor
      instability/sensory urgency remains bladder training, which has proven objective
      efficacy, but new treatments such as transcutaneous electrical nerve stimulation
      (TENS) offer promise. Finally, for certain groups of women with mixed stress and
      urge leak, a new range of vaginal and urethral devices provide useful additional
      options. The specific requirements for future research are discussed.

PMID- 10897323
TI  - Drug therapy for urinary incontinence.
AB  - Drugs used for treatment of urinary incontinence may act on the central nervous
      system (CNS) or peripherally. Few drugs with a defined CNS site of action are
      available for treatment of urine storage disorders; most of those currently used
      have a peripheral site of action. To treat bladder overactivity associated with
      urgency and urge incontinence, antimuscarinic drugs, alpha-adrenoceptor
      antagonists, beta-adrenoceptor agonists, prostaglandin synthesis inhibitors, and
      several other agents most often developed for non-urological indications, are
      employed. Current treatment is based on the use of antimuscarinic drugs, and
      oxybutynin is, despite a high incidence of side-effects, the gold standard.
      Pharmacological treatment of stress incontinence has had limited success, and
      only alpha-adrenoceptor agonists, with and without combination with oestrogens
      have had a documented effect. New drugs, specifically directed at treatment of
      urine storage disorders, are desirable.

PMID- 10897324
TI  - Surgery for urinary incontinence.
AB  - The surgical treatment for genuine stress incontinence will be dependent upon the
      presence or absence of previous surgery, the severity of the incontinence, the
      general medical fitness of the patient, and the expectations of the patient in a
      balance between efficacy and complications. No single operative procedure is the
      first-line treatment for all patients. A patient who is incontinent following
      surgery should not be assumed to have had failed surgery but should be
      appropriately investigated in order to exclude detrusor instability, fistula and
      chronic retention with overflow. Although the treatment of detrusor instability
      is primarily non-surgical, surgical options are available for selected patients
      in whom non-surgical treatment has failed. The management of vesico-vaginal
      fistulae is dependent upon an accurate assessment of the extent of the fistula
      and the absence of co-existing disease while success should be improved by
      centralizing surgical expertise.

PMID- 10897325
TI  - The role of the nurse in urinary incontinence.
AB  - Specialist nursing is dynamic and needs to be sensitive, flexible and responsive
      to changes in care delivery. Clinical, educational, managerial, audit and
      research activities are all integral to the role of the specialist continence
      nurse. Nurse specialists need to be careful that they do not de-skill the role of
      more generalist nurses, but rather enhance their contribution to continence care.
      They also need to work collaboratively with their Specialist Continence
      Physiotherapist colleagues. There is evidence that care in the community setting
      and on ward areas is sub-optimal. Recent audit activities have shown that nurses
      feel comfortable about assessing the person with continence problems but less
      certain about treatment. One way to address this imbalance is through the use of
      care pathways, examples of which are illustrated.

PMID- 10897326
TI  - Coping strategies for women with urinary incontinence.
AB  - Incontinence is a common and complex condition affecting women of all ages,
      social and cultural backgrounds. 'Coping strategies' play an important role for
      managing incontinence and include changes in lifestyle, protection, aids, and
      catheters, whether they are indwelling or intermittent. By the time women seek
      medical advice for urinary incontinence they have usually tried various tactics
      to either limit the leakage or protect themselves from it. The most common
      tactics to limit leakage include fluid restriction, regular toileting, exercises
      and weight reduction. With medical advice, women can change concomitant
      medication that may be exacerbating the problem. Aids for mobilization can also
      have a dramatic effect on the ability to cope with urinary problems. Pads used
      for protection are often unsuitable and some even wear 'home-made' pads in the
      form of rolled up tissue, commonly to save money. Many different types of pads
      are available although women are often ignorant as to what is best for them.
      Catheters should only be used for intractable incontinence and following
      appropriate investigation. When possible intermittent catheterization should be
      considered. It is essential that all women are assessed and investigated before
      any form of containment becomes long-term management.

PMID- 10897327
TI  - Quality of life and urinary incontinence.
AB  - Quality of life assessments have become increasingly important for the assessment
      of urinary incontinent women. The advent of validated condition-specific
      questionnaires with proven reliability and sensitivity to clinical change has
      encouraged their inclusion in clinical trials of continence care. Only by fully
      understanding the impact of urinary incontinence on quality of life of women can
      we hope to improve its treatment.

PMID- 10897329
TI  - Genetic relation of lobular carcinoma in situ, ductal carcinoma in situ, and
      associated invasive carcinoma of the breast.
AB  - AIMS: The mutual relation of lobular carcinoma in situ (LCIS) and ductal
      carcinoma in situ (DCIS) of the breast, as accepted precursor lesions of invasive
      breast cancer, is controversial. Because they display genetic heterogeneity, it
      is not clear how genetically advanced these entities are and what causes the
      transition to an invasive carcinoma. METHODS: Six cases of LCIS, four of them
      with associated lobular invasive carcinoma, four cases of intermediately
      differentiated DCIS with an associated invasive lobular carcinoma, and nine cases
      of intermediately and poorly differentiated DCIS with associated ductal invasive
      carcinoma were investigated by means of comparative genomic hybridisation (CGH)
      after microdissection and immunohistochemical staining of E-cadherin. RESULTS:
      LCIS was characterised by a low average rate of copy number changes, no evidence
      of amplifications, and a high rate of gains and losses of chromosomal material at
      1q and 16q, respectively. A high degree of genetic homology with well
      differentiated DCIS was obvious, as reported previously. The cases of
      intermediately differentiated DCIS with associated lobular invasive components
      and lobular differentiation revealed striking homologies, and a significant
      difference of E-cadherin expression. The comparison of preinvasive and invasive
      breast lesions, irrespective of differentiation within the same patient, revealed
      no specific alteration that might be associated with invasion. Genetic
      alterations seen in invasive carcinoma were not necessarily seen in the adjacent
      precursor lesions. CONCLUSIONS: These results provide strong evidence that
      invasive breast cancer is a disease with multiple cytogenetic subclones already
      present in preinvasive lesions. Moreover, specific CGH alterations associated
      with invasion were not observed. Furthermore, the close genetic association
      between well differentiated and a subgroup of intermediately differentiated DCIS
      and LCIS led to the hypothesis that LCIS and a subgroup of DCIS are different
      phenotypic forms of a common genotype.

PMID- 10897328
TI  - Monoclonal antibodies.
AB  - Monoclonal antibodies are essential tools for many molecular immunology
      investigations. In particular, when used in combination with techniques such as
      epitope mapping and molecular modelling, monoclonal antibodies enable the
      antigenic profiling and visualisation of macromolecular surfaces. In addition,
      monoclonal antibodies have become key components in a vast array of clinical
      laboratory diagnostic tests. Their wide application in detecting and identifying
      serum analytes, cell markers, and pathogenic agents has largely arisen through
      the exquisite specificity of these unique reagents. Furthermore, the continuous
      culture of hybridoma cells that produce these antibodies offers the potential of
      an unlimited supply of reagent. In essence, when compared with the rather limited
      supply of polyclonal antibody reagents, the feature of a continuous supply
      enables the standardisation of both the reagent and the assay technique. Clearly,
      polyclonal and monoclonal antibodies have their advantages and disadvantages in
      terms of generation, cost, and overall applications. Ultimately, monoclonal
      antibodies are only produced when necessary because their production is time
      consuming and frustrating, although greatly rewarding (at least most of the
      time!). This is especially apparent when a monoclonal antibody can be applied
      successfully in a routine pathology laboratory or can aid in the clinical
      diagnosis and treatment of patients. In this article, the generation and
      application of monoclonal antibodies are demystified to enable greater
      understanding and hopefully formulate novel ideas for clinicians and scientists
      alike.

PMID- 10897330
TI  - Expression of pi-class glutathione S-transferase: two populations of high grade
      prostatic intraepithelial neoplasia with different relations to carcinoma.
AB  - BACKGROUND/AIMS: Patients with high grade prostatic intraepithelial neoplasia of
      the transition zone appear to be at increased risk of developing prostatic
      carcinoma, although not to the same degree as patients with high grade prostatic
      intraepithelial neoplasia of the peripheral/central zone. Previous investigations
      have shown loss of expression of pi-class glutathione S-transferase (GST-pi; an
      enzyme that protects against electrophilic carcinogens) in prostatic carcinoma
      and in high grade prostatic intraepithelial neoplasia. The aim of this study was
      to compare the expression of GST-pi in high grade prostatic intraepithelial
      neoplasia of the transition zone with that in high grade prostatic
      intraepithelial neoplasia of the peripheral/central zone (that is, non-transition
      zone). METHODS: Immunostaining with the anti-GST-pi antibody was performed on 20
      high grade prostatic intraepithelial neoplasia samples of the transition zone,
      either isolated or associated with prostatic carcinoma (groups 1 and 2,
      respectively; 10 cases each) and on 20 high grade prostatic intraepithelial
      neoplasia samples of the non-transition zone, either isolated or associated with
      prostatic carcinoma (groups 3 and 4, respectively; 10 cases each). This study
      also included six samples of high grade prostatic intraepithelial neoplasia
      simultaneously present in the transition and non-transition zones and not
      associated with prostatic carcinoma (group 5). The presence of immunostaining,
      staining intensity, and the distribution of immunostaining were evaluated in the
      high grade prostatic intraepithelial neoplasia lesions and in the normal tissue
      and cancer areas. RESULTS: The GST-pi antibody stained the cytoplasm of the cells
      lining the ducts and acini of normal prostate tissue. Staining was stronger and
      more diffuse in the basal cell layer than in the luminal (or secretory) cell
      layer. Immunohistochemical staining with anti-GST-pi antibodies failed to detect
      the enzyme in all prostatic carcinoma foci but one. Two patterns were detected in
      high grade prostatic intraepithelial neoplasia. One was represented by GST-pi
      staining similar to that of the normal tissue (pattern A). The other deviated
      from it and was characterised by absence of GST-pi expression in the secretory
      cells and abundant expression in scattered basal cells (pattern B). Pattern A
      staining was seen more frequently in the transition than in the non-transition
      zone. Pattern B staining was seen mainly in high grade prostatic intraepithelial
      neoplasia of non-transition zone associated with cancer. CONCLUSIONS: The
      differential expression of GST-pi in the transition and non-transition zones
      indicates the existence of two populations with the morphological appearance of
      high grade prostatic intraepithelial neoplasia that might have different
      associations with carcinoma.

PMID- 10897331
TI  - Interphase argyrophilic nucleolar organiser regions and nucleolar counts in
      transitional cell bladder tumours.
AB  - AIMS: To see whether a correlation exists between clinicopathological parameters,
      argyrophilic nucleolar organiser regions (AgNORs), and nucleolar counts in the
      nuclei of tumour cells in patients with transitional cell bladder carcinoma.
      METHODS: Paraffin wax embedded sections from a total of 62 cases of primary
      transitional cell bladder carcinoma were stained with the silver colloid method.
      The numbers of individual silver grains (AgNORs) in nucleoli and the numbers of
      nucleoli were counted in 100 nuclei. The correlation between AgNORs and nucleolar
      counts and patients' sex, tumour grade, disease stage, recurrence pattern, and
      tumour related survival was analysed. RESULTS: The numbers of nucleoli in tumour
      cells were higher in male patients (p < 0.032). AgNOR numbers correlated with
      tumour grade (p = 0.017) and recurrence (p = 0.046). In multivariate analysis,
      the variation coefficient of AgNOR scores was found to be the only independent
      predictor of the duration of tumour free period in patients with recurrent
      disease (p < 0.002). AgNOR scores and nucleolar counts were of no value in
      distinguishing superficial and invasive tumours or in predicting tumour related
      survival. CONCLUSIONS: AgNOR scores in transitional cell bladder carcinoma
      reflect variations in tumour biological behaviour; however, the clinical value of
      this technique in patients with urinary bladder carcinoma is limited.

PMID- 10897332
TI  - Telomerase activity in pancreatic endocrine tumours: a potential marker for
      malignancy.
AB  - AIMS: Telomerase activation is known to be a common event in human cancer and may
      be a useful marker for malignancy. In general, the histological features of
      pancreatic endocrine tumours cannot be used to determine their malignant
      potential. The aim of this study was to investigate the role of testing
      telomerase activity in pancreatic endocrine tumours. METHODS: Prospectively
      collected fresh frozen tissue specimens from 10 patients with pancreatic
      endocrine tumours (nine insulinomas, one adrenocorticotrophin producing
      pancreatic endocrine tumour) were examined by a highly sensitive polymerase chain
      reaction (PCR) based telomerase repeat protocol (TRAP). RESULTS: Of the 10
      pancreatic endocrine tumours, three had telomerase activity. The positive cases
      included two frankly malignant tumours with liver metastases and one pancreatic
      endocrine tumour occurring in the setting of multiple endocrine neoplasia type 1.
      The latter had an infiltrative border. Vascular and perineural tumour
      infiltration was noted. In the two malignant pancreatic endocrine tumours with
      liver metastases, telomerase activity was noted in the tumour and the adjacent
      morphologically non-neoplastic pancreas. CONCLUSION: To our knowledge, this is
      the first report of the role of telomerase activity in pancreatic endocrine
      tumours. Telomerase activity might be useful for distinguishing between benign
      and malignant pancreatic endocrine tumours.

PMID- 10897333
TI  - Role of chromosome 3p12-p21 tumour suppressor genes in clear cell renal cell
      carcinoma: analysis of VHL dependent and VHL independent pathways of
      tumorigenesis.
AB  - AIMS: Chromosome 3p deletions and loss of heterozygosity (LOH) for 3p markers are
      features of clear cell renal cell carcinoma but are rare in non-clear cell renal
      cell carcinoma. The VHL tumour suppressor gene, which maps to 3p25, is a major
      gatekeeper gene for clear cell renal cell carcinoma and is inactivated in most
      sporadic cases of this disease. However, it has been suggested that inactivation
      of other 3p tumour suppressor genes might be crucial for clear cell renal cell
      carcinoma tumorigenesis, with inactivation (VHL negative) and without
      inactivation (VHL positive) of the VHL tumour suppressor gene. This study set out
      to investigate the role of non-VHL tumour suppressor genes in VHL negative and
      VHL positive clear cell renal cell carcinoma. METHODS: Eighty two clear cell
      renal cell carcinomas of known VHL inactivation status were analysed for LOH at
      polymorphic loci within the candidate crucial regions for chromosome 3p tumour
      suppressor genes (3p25, LCTSGR1 at 3p21.3, LCTSGR2 at 3p12 and at 3p14.2).
      RESULTS: Chromosome 3p12-p21 LOH was frequent both in VHL negative and VHL
      positive clear cell renal cell carcinoma. However, although the frequency of 3p25
      LOH in VHL negative clear cell renal cell carcinoma was similar to that at 3p12
      p21, VHL positive tumours demonstrated significantly less LOH at 3p25 than at
      3p12-p21. Although there was evidence of LOH for clear cell renal cell carcinoma
      tumour suppressor genes at 3p21, 3p14.2, and 3p12, both in VHL negative and VHL
      positive tumours, the major clear cell renal cell carcinoma LOH region mapped to
      3p21.3, close to the lung cancer tumour suppressor gene region 1 (LCTSGR1). There
      was no association between tumour VHL status and tumour grade and stage.
      CONCLUSIONS: These findings further indicate that VHL inactivation is not
      sufficient to initiate clear cell renal cell carcinoma and that loss of a
      gatekeeper 3p21 tumour suppressor gene is a crucial event for renal cell
      carcinoma development in both VHL negative and VHL positive clear cell renal cell
      carcinoma.

PMID- 10897334
TI  - Expression of the matrix metalloproteinase 9 in Hodgkin's disease is independent
      of EBV status.
AB  - BACKGROUND: In vitro the Epstein-Barr virus (EBV) encoded latent membrane protein
      1 (LMP-1) has been shown to upregulate expression of matrix metalloproteinase 9
      (MMP-9), a member of a family of zinc dependent endopeptidases that is believed
      to facilitate tumour invasion and metastasis by degradation of the extracellular
      matrix. AIM: To test whether the expression of MMP-9 in Hodgkin's disease
      correlates with EBV status and survival and to investigate whether LMP-1
      expression affects MMP-9 concentrations in the Hodgkin's disease cell line, L428.
      METHODS: MMP-9 expression was measured by means of immunohistochemistry in a
      series of Hodgkin's disease tumours and this expression was correlated with EBV
      status and survival. The influence of LMP-1 on MMP-9 expression was also
      investigated in the Hodgkin's disease cell line, L428. RESULTS: MMP-9 expression
      was demonstrated in the malignant Hodgkin and Reed-Sternberg cells of all (n =
      86) formalin fixed, paraffin wax embedded Hodgkin's disease tumours examined.
      Although the intensity of MMP-9 immunostaining varied between cases, there was no
      correlation between MMP-9 expression and EBV status or survival. MMP-9 expression
      was also detected in a variety of non-malignant cells, including fibroblasts. MMP
      9 was detected by zymography in the L428 and KMH2 Hodgkin's disease cell lines,
      whereas low or undetectable amounts of MMP-9 were found in the L591 Hodgkin's
      disease cell line. Induction of LMP-1 expression in the Hodgkin's disease cell
      line L428 did not result in a detectable increase in the values of MMP-9 as
      measured by zymography. CONCLUSIONS: These results demonstrate that MMP-9 is
      consistently expressed by the Hodgkin and Reed-Sternberg cells of Hodgkin's
      disease tumours and by the Hodgkin's disease cell lines, L428 and KMH2. However,
      this expression does not appear to be related either to LMP-1 values or to
      survival.

PMID- 10897335
TI  - Detection of clonal T cell populations by high resolution PCR using fluorescently
      labelled nucleotides; evaluation using conventional LIS-SSCP.
AB  - AIMS: To detect clonal T cell populations by high resolution polymerase chain
      reaction (PCR) using fluorescently labelled nucleotides and analysis on an ABI
      377 DNA sequencer, and to evaluate this method using low ionic strength single
      strand conformation polymorphism (LIS-SSCP) analysis. METHODS: DNA samples from
      11 patients diagnosed with a T cell disease and 15 with no known T cell disorder
      were amplified using four multiplex T cell receptor gamma (TCR gamma) PCR
      reactions containing fluorescently labelled nucleotides. PCR products were
      analysed using both LIS-SSCP electrophoresis and an ABI 377 DNA sequencer using
      Genescan software. A Jurkat T cell leukaemia cell line was used to determine the
      sensitivity of the two methods. RESULTS: Clonal TCR gamma populations were
      detected in all 11 samples from patients with a T cell disease and no clonal
      populations were detected in samples from patients without a T cell disorder,
      using both LIS-SSCP and DNA sequencer analysis. Although the sensitivity of the
      two methods was comparable, the data generated by the sequencer were easier to
      interpret than the LIS-SSCP gels, and allowed accurate size determination of
      every product, which was not possible using LIS-SSCP. CONCLUSIONS: The use of
      fluorescent labelled nucleotides provides a more flexible and economical
      alternative to end labelled fluorescent primers for the detection of clonal TCR
      gamma gene rearrangements. This method allows clonal populations to be sized
      accurately and reproducibly, permitting the detection of identical clonal
      populations in different samples, and providing a method of monitoring disease
      progression and response to treatment.

PMID- 10897337
TI  - Selective genetic analysis of p53 immunostain positive cells.
AB  - The isolation of p53 immunostain positive cells from histological sections for
      molecular genetic studies is a difficult task, especially if there are few
      positive cells. To eliminate contaminating DNA from p53 negative cells, which can
      obscure the results of molecular assays, a variation on the technique of
      immunohistoselective sequencing was developed. This is a highly selective
      approach, whereby immunostained sections of formalin fixed, paraffin wax embedded
      tissue are exposed to ultraviolet irradiation to damage the DNA in p53 negative
      cells. The DNA in positive cells remains unaffected because the dark immunostain
      protects their nuclei from ultraviolet light. Polymerase chain reaction single
      strand conformation polymorphism of samples enriched with p53 immunostain
      positive cells has shown that this method can produce pure samples of mutated
      DNA. The isolation of DNA from minority immunostain positive cells allows a wide
      range of molecular analyses to be carried out on these samples, which would
      otherwise be hampered by the problem of contaminating background cells.

PMID- 10897336
TI  - Immunoblotting can help the diagnosis of ocular toxoplasmosis.
AB  - AIMS: To determine whether IgG immunoblotting can improve the diagnosis of ocular
      toxoplasmosis. METHODS: Samples of serum were tested from patients with ocular
      lesions that could be caused by toxoplasmosis. All such samples from Scotland and
      Northern Ireland are usually referred to the Scottish Toxoplasma Reference
      Laboratory. From questionnaires filled out by the clinicians, two groups of sera
      were identified: ocular toxoplasmosis (active and quiescent), n = 54 (group 1);
      and eye disease as a result of other causes, n = 36 (group 2). Control groups
      were made up of sera from patients with no eye disease and a normal dye test
      result (< or = 125 IU/ml), n = 16 (group 3); and toxoplasma seronegative,
      cytomegalovirus (CMV) positive, and herpes simplex virus (HSV) positive sera
      (group 4), n = 18. RESULTS: Immunoblots with an active pattern could be
      identified (IgG antibodies against at least four antigens with molecular weight
      of 6, 20, 22, 23, 25, and 36 kDa). Significantly more of this pattern was found
      in group 1 (33 of 54; 61.1%) compared with group 2 (nine of 36; 25%) or group 3
      (six of 16; 37.5%). Within group 1, significantly more sera with an active
      pattern had dye test results > or = 65 IU/ml compared with those without. More
      sera from patients < 30 years of age were found with the active pattern in group
      1 compared with group 2. No group 4 sera had active immunoblot patterns.
      CONCLUSIONS: The immunoblot result adds more support to the diagnosis of ocular
      toxoplasmosis. In cases where the clinical diagnosis is difficult, immunoblots
      are particularly indicated; if negative, other causes of eye disease should be
      sought.

PMID- 10897338
TI  - Detection of Epstein-Barr virus in archival Hodgkin's disease specimens.

PMID- 10897339
TI  - Improving the reliability of visual acuity measures in young children.
AB  - Whilst the methodology of adult letter acuity measurement has been substantially
      refined over the last two decades, relatively little development has occurred in
      methods for quantifying letter acuity in young children. This study compares a
      recently developed visual acuity test (Glasgow Acuity Cards), which incorporates
      several key design features used in adult test charts to improve the sensitivity
      and reliability of visual acuity measurements. The equivalence of acuity
      measurements made with Glasgow Acuity Cards were compared with the Bailey-Lovie
      logMAR chart and Snellen chart in adults, and with traditional Single Letter
      Acuity and a modified Single Letter Acuity test in children. The test-retest
      reliability of acuity measurements made with Glasgow Acuity Cards and the Single
      Letter Acuity tests were also assessed in a large group of visually normal
      children. In addition, the ability of the pre-school letter acuity tests to
      detect differences in acuity between the two eyes, and to detect amblyopia were
      examined. Ninety-five percent of vision measurements made with the Bailey-Lovie
      chart and Glasgow Acuity Cards differ by less than 0.07 log unit. Furthermore,
      the sensitivity of Glasgow Acuity Cards to detecting changes in acuity
      longitudinally and inter-ocular differences in acuity is considerably greater as
      compared with traditional Single Letter Acuity tests. Improvements in paediatric
      acuity chart design are important for the effective detection and management of
      children with amblyopia.

PMID- 10897340
TI  - Near visual function in young children. Part I: Near point of convergence. Part
      II: Amplitude of accommodation. Part III: Near heterophoria.

PMID- 10897341
TI  - The effect of prism adaptation on the response AC/A ratio.
AB  - Vergence adaptation, also known as prism adaptation, is a phenomenon in which a
      patient's heterophoria changes after prolonged viewing through prism. The effect
      of prism adaptation on the accommodation-convergence relationship, quantified by
      the AC/A ratio, is not known. Previous studies of AC/A ratio stability and
      alterability have used only stimulus AC/A ratio calculations, or have measured
      accommodative responses to only one or two stimuli. The ideal study of AC/A ratio
      stability and alterability would measure accommodative responses to several
      accommodative stimuli, and use these along with vergence responses to calculate
      response AC/A ratios, rather than stimulus AC/A ratios. In addition, the gradient
      method should be used to avoid any effect of proximal vergence resulting from
      changes in target distance. This paper describes a project which investigated the
      effect of vergence (prism) adaptation on the gradient response AC/A ratio, using
      accommodative responses measured for five different accommodative stimuli. The
      response AC/A ratio did not significantly change following a period of adaptation
      to base-in prism for six of the eight subjects in this study. In addition, the
      response AC/A ratio did not significantly change following a period of adaptation
      to base-out prism for six of the eight subjects.

PMID- 10897342
TI  - Vergence adaptation and the clinical AC/A ratio.
AB  - The accuracy of the gradient technique for measuring the clinical accommodative
      convergence to accommodation (AC/A) ratio is dependent upon obtaining veridical
      heterophoria measurements. However, previous studies have demonstrated that the
      sustained output of slow fusional vergence, which may take several minutes or
      even hours to decay, can bias heterophoria assessment. In the clinical setting,
      it is usual to estimate the AC/A ratio after just a few seconds of dissociation.
      This study investigated whether the slow fusional vergence response alters this
      crosslink ratio by comparing values of AC/A measured both before and immediately
      after a 1-hr period of continuous monocular occlusion. Sustained occlusion
      produced a significant change in near heterophoria in 10 out of the 21 subjects
      examined, but no significant change in AC/A was observed in either the adapting
      or non-adapting subgroups. Accordingly, while the sustained output of slow
      fusional vergence will influence clinical measurements of heterophoria, its
      presence does not alter the stimulus AC/A ratio significantly.

PMID- 10897343
TI  - Characteristics of a paediatric low vision population in a private eye hospital
      in India.
AB  - While private hospitals provide an important access point for low vision services
      for children in urban India, little is known about this service delivery route. A
      cross sectional survey was done of consecutive records of 220 children presenting
      at a newly opened paediatric low vision centre in a private eye hospital in
      Hyderabad. On presentation, 49% of the children were classified as moderately
      visually impaired, 31% were severely visually impaired and 20% were blind. The
      four major causes of visual impairment were the hereditary/genetic conditions of
      congenital glaucoma, hereditary macular degeneration, retinitis pigmentosa and
      albinism. Approach magnification was sufficient for required near tasks in all
      pre-school children and about 50% of school children. Provision of a distance
      refraction decreased the prevalence of severe visual impairment and blindness by
      31%. The most commonly prescribed low vision devices were spectacles indicating a
      key role for optometry in the management of visual impairment in Indian children.
      Establishment of low vision clinics in existing Indian eye hospitals using
      associated optometric staff would be a cost effective method to minimise visual
      impairment in Indian children.

PMID- 10897344
TI  - The three point vernier alignment or acuity test (3Pt VA test): an analysis of
      variance.
AB  - A very useful clinical vernier acuity or vernier alignment test has been
      developed in this and associated laboratories over a span of two decades. We seek
      to refine further this test, to seek internal inconsistencies and to optimize
      parameters used in a variety of devices and environments. Vernier testing, and
      many aspects of this work have been considered by numerous able scientists over a
      long time period (not reviewed here), but none have encountered conditions faced
      by this group, particularly in the developing world. The three point vernier
      alignment (acuity) threshold test (3Pt VeA test) employed here has broad
      applications; it can be used as a clinical test of vision status, for triage, and
      as a reference standard for vision testing (in general). As one example, if
      sufficient luminance is employed, the test is applicable in the presence of truly
      dense media disorders, even advanced leucomas, mature cataracts, intraocular
      bleeds, as well as combinations of these disorders, with or without a window to
      the retina. Only retinal and centrally-based neural disorders, eccentricity from
      fixation, and about 50% of hypermature cataracts affect outcomes. With minor
      alterations, this test can be employed to assess the visual field. An analysis of
      variance (ANOVA) was performed on a defined set of parameters, to enable us to
      understand better the special properties and requirements associated with this
      test. Results are not significantly altered between ages 10-94 years (not
      assessed here). Employing settings well above threshold for test spot detection
      and well separated individual test spots, changes in test spot luminance, or
      background luminance (or adaptation level), contrast, veiling glare, test spot
      size, clear and variously degraded images, seem not to affect meaningfully
      measured outcomes. If an observer can define well a center of gravity for each
      test spot viewed, he can align the three points with remarkable precision.

PMID- 10897345
TI  - An introduction to analysis of variance (ANOVA) with special reference to data
      from clinical experiments in optometry.
AB  - This article is aimed primarily at eye care practitioners who are undertaking
      advanced clinical research, and who wish to apply analysis of variance (ANOVA) to
      their data. ANOVA is a data analysis method of great utility and flexibility.
      This article describes why and how ANOVA was developed, the basic logic which
      underlies the method and the assumptions that the method makes for it to be
      validly applied to data from clinical experiments in optometry. The application
      of the method to the analysis of a simple data set is then described. In
      addition, the methods available for making planned comparisons between treatment
      means and for making post hoc tests are evaluated. The problem of determining the
      number of replicates or patients required in a given experimental situation is
      also discussed.

PMID- 10897346
TI  - Modelling adaptation effects in vergence and accommodation after exposure to a
      simulated virtual reality stimulus.
AB  - Natural viewing conditions place equal demands on the vergence and accommodation
      systems. The two responses are co-ordinated via the interactive components which
      couple the two systems: accommodative vergence and vergence accommodation. The
      crosslink components are usually quantified by the AC/A and CA/C ratios. Whether
      these ratios are stable entities, genetically determined, or modifiable by
      experience has been the subject of some debate. A 'Virtual Reality' stimulus was
      used to place unequal demands on the vergence and accommodation systems. Pre-task
      and post-task measures of AC/A and CA/C were objectively determined. The changes
      in the post-task measures are discussed with reference to a dual interactive
      model of vergence and accommodation. Model simulations suggest that adaptation of
      the vergence and accommodative controllers (tonic adaptation) may also play a
      part by altering the open loop bias. The results therefore support the idea that
      vergence accommodation and accommodative vergence are capable of adaptation.

PMID- 10897347
TI  - Towards a colorimetric characterization of the human iris.
AB  - We propose a new approach to the quantitative determination of the iris colour
      through the spectroradiometric measurement of a set of 72 artificial irises under
      controlled illumination and geometry. The spread of these samples in the CIELAB
      colour space indicates no clearly distinguished groups within the set analysed.
      Colour measurements for different points of these irises and for the overall
      irises (pupil and specular image of the light source included) are well
      correlated. Complementary colour measurements were also performed for the irises
      of 25 ocular prostheses and 40 real observers. All these colour measurements
      appear to be quite consistent, the average standard deviation of any of the three
      a*, b*, L* co-ordinates being lower than 1.0 units. In a visual experiment where
      11 normal observers matched the 25 ocular prostheses using the 72 artificial
      irises, the results indicate that a simple criterion based on the lowest colour
      difference agreed with the observers' judgements in only 18% of the cases. This
      result suggests that, although colour appears to be a major parameter in the
      overall characterization of the human iris, additional factors such as patterns
      or textures should also be considered.

PMID- 10897349
TI  - The resurgence of tuberculosis in the tropics. Improving tuberculosis control-
      social science inputs.
AB  - Public health has for long been dominated by the notion of 'control'. However,
      social science research on tuberculosis in the tropics indicates that policies
      and programmes that take 'control' as their primary focus may fail to meet the
      health needs of patients and their communities. It is proposed that research and
      programmes meet the public health goal of lowering the prevalence of disease in
      populations by forging and cementing partnerships which take the support and care
      of patients as their focus. These will be partnerships between researchers in the
      North and the South, between research and programmes/policy, between outside
      'experts' and communities themselves and between (public) health and other social
      service sectors. Social science approaches to operations research in tuberculosis
      are outlined, and data from a recent project in New Delhi are introduced.

PMID- 10897348
TI  - Annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa:
      literature survey, Internet access and review.
AB  - This paper presents the results of an extensive search of the formal and informal
      literature on annual Plasmodium falciparum entomological inoculation rates (EIR)
      across Africa from 1980 onwards. It first describes how the annual EIR data were
      collated, summarized, geo-referenced and staged for public access on the
      internet. Problems of data standardization, reporting accuracy and the subsequent
      publishing of information on the internet follow. The review was conducted
      primarily to investigate the spatial heterogeneity of malaria exposure in Africa
      and supports the idea of highly heterogeneous risk at the continental, regional
      and country levels. The implications for malaria control of the significant
      spatial (and seasonal) variation in exposure to infected mosquito bites are
      discussed.

PMID- 10897350
TI  - The resurgence of tuberculosis in the tropics. An engineering approach to the
      control of Mycobacterium tuberculosis and other airborne pathogens: a UK hospital
      based pilot study.
AB  - The world-wide occurrence of tuberculosis (TB) is very high, and in many parts of
      the world prevalence has reached epidemic proportions. While the WHO's global
      'directly observed therapy short-course' (DOTS) programme has yielded some
      notable successes, it has reached only 12% of the world's TB cases (1996 data).
      This suggests that the use of drug therapy alone is not enough to solve the
      global TB problem and that prevention using public health engineering techniques
      may provide a complementary solution. There are a number of engineering control
      strategies, such as the use of ultraviolet germicidal irradiation (UVGI) and
      advanced ventilation techniques, which can be used to combat the spread of
      Mycobacterium tuberculosis and other airborne pathogens. This paper describes a
      pilot study currently being undertaken at the Leeds General Infirmary in the UK,
      which is investigating the use of UVGI to disinfect air in ward spaces.

PMID- 10897351
TI  - Tropical diseases in ancient Egypt.

PMID- 10897353
TI  - Socio-economics of visceral leishmaniasis in Bihar (India).

PMID- 10897352
TI  - Visceral leishmaniasis in Sudan: first identifications of Leishmania from dogs.

PMID- 10897354
TI  - Japanese encephalitis among paediatric patients with acute encephalitis syndrome
      in Tamil Nadu, India.

PMID- 10897355
TI  - Local-scale variation in malaria infection amongst rural Gambian children
      estimated by satellite remote sensing.
AB  - We investigated local-scale variation in malaria transmission and infection in
      children within a continuous landscape by retrospective spatial analysis of
      entomological and clinical data collected during 1988 and 1989 in The Gambia,
      West Africa. Parasite prevalence was negatively correlated with vector abundance
      and exposure to malaria parasites in 10 villages where entomological surveillance
      had been carried out. Variation in bednet use did not explain this finding.
      Mosquito-breeding habitat was retrospectively mapped using 20-m spatial
      resolution multispectral SPOT satellite imagery from 1988. From these data we
      estimated by linear regression the risk of exposure to malaria parasites in 26
      villages where clinical surveys of children had been made. As exposure increased,
      so did parasite prevalence; but at higher levels of exposure, parasite prevalence
      declined. Our findings demonstrate marked differences in exposure to malaria in
      villages over distances of less than 2 km from mosquito breeding sites and
      suggest that there are also large differences in immunity between neighbouring
      settlements.

PMID- 10897356
TI  - The epidemiology of leishmaniases in Lebanon.
AB  - The prevalence of leishmaniasis in Lebanon was studied in 1993-97 for a Lebanese
      population sample of about 81,000 subjects (60% rural and 40% urban) constituting
      roughly 3.4% of the total population. The prevalence of cutaneous leishmaniasis
      was found to be 0.18% in the rural versus 0.41% in the urban areas. Visceral
      leishmaniasis was practically non-existent in both environments. In addition,
      skin tests were done and anti-Leishmania antibodies were sought in a sample of
      the population at risk in the rural area. Skin tests were positive in 2.5% of the
      tested subjects, and 1% of the normal population had elevated levels of anti
      Leishmania antibodies. The difference between the prevalence of clinical disease
      and positive skin testing and/or antibodies may be due to the existence of past
      or present subclinical disease. An unexpected finding was that the prevalent
      dermotropic parasite in Lebanon belongs to the L. donovani complex. Further
      characterization of the isolates by molecular techniques and definition of the
      transmission cycle of this parasite may explain our epidemiological findings.

PMID- 10897357
TI  - Contrasting incidence of Clostridium difficile and other enteropathogens in AIDS
      patients in London and Lusaka.

PMID- 10897358
TI  - Disappearance of pan-malarial antigen reactivity using the ICT Malaria P.f/P.v
      kit parallels decline of patent parasitaemia as shown by microscopy.

PMID- 10897359
TI  - Cross-reactivity of anti-Plasmodium falciparum antibodies and HIV tests.

PMID- 10897360
TI  - Evaluation of a 200-kDa amastigote-specific antigen of L. donovani by enzyme
      linked immunosorbent assay (ELISA) for the diagnosis of visceral leishmaniasis.
AB  - A purified 200-kDa antigenic fraction from Leishmania donovani axenic amastigotes
      was evaluated by ELISA for the detection of antibody response in visceral
      leishmaniasis (VL) patients, post kala-azar dermal leishmaniasis (PKDL) patients
      and controls, for the diagnosis of visceral leishmaniasis. A positive antibody
      response to the 200-kDa amastigote fraction and to Leishmania amastigote soluble
      antigen (LASA) was found in 29 (96.6%) and 30 ((100%) confirmed VL patients,
      respectively, by the use of ELISA. However, only 1 (10%) out of 10 PKDL patients
      had detectable antibody response to 200-kDa fraction while all the 10 (100%) PKDL
      patients exhibited an immune response to LASA. Therefore, use of the 200-kDa
      antigenic fraction for the detection of antibody response in an ELISA follow-up
      (post treatment) of VL patients may have prognostic significance, and it may also
      be useful for differentiating active VL and PKDL.

PMID- 10897361
TI  - An improved Knott's concentration test for the detection of microfilariae.

PMID- 10897362
TI  - Clinical epidemiology and classification of human oesophagostomiasis.
AB  - The intestinal helminth Oesophagostomum bifurcum is highly and focally endemic in
      northern Ghana and Togo, and its juveniles produce a nodular inflammatory
      response as they develop in the intestinal wall. This pathology can produce
      clinical symptoms. We report on 156 cases of oesophagostomiasis presenting in
      1996-98 to Nalerigu hospital in northern Ghana. The disease accounted for 0.2% of
      the out-patient department new presentations (about 1 patient per week), and 1%
      (16) of the major acute surgical cases. Children aged 5-9 years were most
      commonly affected. Multinodular disease (13% of the cases) results from hundreds
      of pea-sized nodules within the colon wall and other intra-abdominal structures,
      and presents with general abdominal pain, persistent diarrhoea and weight loss.
      Dapaong tumour (87%) presents as an abdominal inflammatory mass often associated
      with fever. The 3-6-cm tumour is painful, well-delineated, smooth, spherical,
      'wooden', periumbilical, and adhered to the abdominal wall. Cases most commonly
      presented during the late rains and early dry season. Diagnosis by ultrasound has
      reduced the need for exploratory surgery, and the ability to sonographically
      evaluate conservative treatment with albendazole has curtailed management by
      colectomy or incision and drainage.

PMID- 10897363
TI  - Adults with cerebral malaria do not have sensory evoked responses typical of deep
      general anaesthesia.

PMID- 10897364
TI  - Pentatrichomonas hominis in empyema thoracis.

PMID- 10897365
TI  - Disseminated Penicillium marneffei infection in an African AIDS patient.

PMID- 10897366
TI  - Sulfadoxine-pyrimethamine for the treatment of Plasmodium falciparum malaria in
      Gabonese children.
AB  - Chloroquine can no longer be recommended as the first-line treatment for
      falciparum malaria in several parts of Africa, given the increasing resistance of
      Plasmodium falciparum to this drug. The sulfadoxine-pyrimethamine combination
      (SP) is obviously an alternative candidate, that has already been selected as
      first-line antimalarial treatment by a few African countries. However, the extent
      of resistance to SP appears to be highly variable within Africa. Therefore, we
      investigated the efficacy of SP to treat uncomplicated malaria attacks in
      children from south-east Gabon. Sixty-six children presenting with a P.
      falciparum malaria attack were given a standard regimen of SP, and were followed
      at Days 3, 7, 14, and 21. No RIII response was observed, but relatively high
      prevalences of RII (18.2%) and RI (12.1%) were present. Moreover, analysis of the
      clinical outcome according to CDC criteria showed that initial clinical response
      was lacking in 8.5% of children, and that clinical failure occurred in 9.1%.

PMID- 10897367
TI  - Two-year impact of praziquantel treatment for Schistosoma japonicum infection in
      China: re-infection, subclinical disease and fibrosis marker measurements.
AB  - We studied a community cohort of 193 individuals exposed to endemic Schistosoma
      japonicum infection in the Dongting Lake region of China to assess subclinical
      morbidity and the 2-year benefit of curative therapy (praziquantel) administered
      in 1996. Prevalence and intensity of S. japonicum infection before treatment were
      28% and 192 eggs per gram faeces (epg), respectively. Two years after cure, 22%
      of the cohort were re-infected, but with a lighter intensity (67 epg). Sixty-four
      subjects (37%) showed significant improvement in ultrasound parenchyma images
      after treatment and 51 subjects (54%) showed significant improvement of
      periportal fibrosis. Left-lobe enlargement also reversed (P < 0.05) and
      splenomegaly reversed in 6 of 8 cases and developed in only 1. Two years post
      treatment a dilated portal vein became less frequent, but the decline was not
      significant (16% vs 11%, P < 0.05). The serum levels of laminin and collagen IV
      associated with re-infection and intensity and hyaluronic acid levels correlated
      with ultrasound findings (P < 0.01). Overall, treatment induced a marked decrease
      in subclinical hepatosplenic morbidity attributable to S. japonicum although low
      intensity re-infection after treatment remained relatively frequent. Stratified
      analysis and logistic models evaluated potential confounding factors for
      assessment of treatment effects on hepatic fibrosis. S. japonicum infection and
      moderate-heavy alcohol intake interacted: improvement in parenchymal morbidity
      was impeded among drinkers (P < 0.05). Chemotherapy focused on at-risk residents
      controls prevalent subclinical hepatic fibrosis but re-infection indicates the
      need for complementary control strategies.

PMID- 10897368
TI  - Selected chemotherapy and seasonally transmitted Schistosoma haematobium
      infections in the middle valley of the Senegal River Basin.

PMID- 10897369
TI  - Short-course, cost-effective treatment with amphotericin B-fat emulsion cures
      visceral leishmaniasis.
AB  - Although short-course therapy with new lipid formulations of amphotericin B
      represents an advance over lengthy traditional treatments in visceral
      leishmaniasis (kala-azar), high cost has rendered these agents largely irrelevant
      in developing countries where the disease is endemic. Therefore, we tested
      standard amphotericin B deoxycholate mixed with a commercial fat emulsion as
      short-course treatment for Indian visceral leishmaniasis in Bihar in 1997/98.
      Seventy children and adults with splenic aspirate-documented infection, 23 of
      whom had failed prior antimony (Sb) therapy, received 5 alternate-day infusions
      of 2 mg/kg. Apparent cure, which required a parasite-free splenic aspirate smear,
      was assessed 20 days after treatment (day 30); definitive cure was determined at
      6 months. Other than anticipated infusion-related fever and/or chills, treatment
      was safe and well tolerated. One patient required dose modification because of
      mild, reversible renal insufficiency. Sixty-nine patients (98.6%, CI 92.3-100%)
      had apparent cures; during follow-up, there were 4 treatment failures (relapses,
      3; unrelated death, 1), yielding definitive cures in 65 of 70 patients (92.9%, CI
      84.1-97.6%). Including retreatment costs for patients in Bihar (who now often
      fail initial Sb therapy), the final per patient cost of the tested regimen (US
      $260) was 59% and 43% less than treatment with Sb or conventional amphotericin B
      alone, respectively. Short-course treatment with amphotericin B-fat emulsion is
      active, cost-effective treatment for patients with visceral leishmaniasis
      including those with Sb-unresponsive infection.

PMID- 10897370
TI  - A randomized double-blind placebo-controlled field trial of ivermectin and
      albendazole alone and in combination for the treatment of lymphatic filariasis in
      Ghana.
AB  - The efficacy and safety of single-dose ivermectin (150-200 micrograms/kg) and
      albendazole (400 mg) treatment administered separately or in combination for
      Wuchereria bancrofti infections were assessed in 1996-98 in a randomized double
      blind placebo-controlled field trial in Ghana: 1425 individuals from 4 lymphatic
      filariasis-endemic villages, 340 of whom were microfilaria (mf)-positive before
      treatment, were randomized into 4 groups to receive albendazole alone, ivermectin
      alone, combination of albendazole and ivermectin, or placebo, respectively.
      Individuals were followed for 5 days after treatment to record any adverse
      reactions, and the effect of treatment on microfilaraemia was monitored in night
      blood samples after 3, 6 and 12 months. Treatment efficacy was analysed for 236
      mf-positive individuals who had > or = 100 mf/mL of blood and who were also
      present for examination at 12 months after treatment. Compared to the placebo
      group, the ivermectin and combination groups both showed statistically
      significant reductions in geometric mean mf intensities at the follow-up
      examinations (to 6.7% and 0.9%, 9.9% and 6.9%, and 21.7% and 11.4% of pre
      treatment levels, respectively, at 3, 6 and 12 months after treatment). Compared
      to the ivermectin group, however, the reduction in the combination group was
      significantly greater only at 3 months after treatment, but not after 6 or 12
      months. The albendazole group showed a slow but non-significant reduction over
      the same period. Adverse reactions were few and mostly mild (no severe reactions
      were recorded), and no significant differences were observed between the
      treatment groups. Both ivermectin and combination treatment thus appeared
      effective and safe for treatment of lymphatic filariasis, but the difference in
      efficacy was minor and the study did not provide clear evidence for the
      combination drug therapy, as compared to ivermectin therapy alone, to be superior
      for control of lymphatic filariasis.

PMID- 10897371
TI  - Antibiotic susceptibility and genotypes of non-typhi Salmonella isolates from
      children in Kilifi on the Kenya coast.
AB  - A 4-year retrospective study was undertaken at the Kilifi District Hospital on
      the coast of Kenya to determine the antibiotic-susceptibility patterns and
      genotypes of non-typhi Salmonella (NTS) isolates from children. Overall, during
      the period 1994-97, positive cultures were obtained from 543 (14%) of 3885 blood
      samples, 364 (30%) of 1210 stool samples and 143 (11%) of 1283 cerebrospinal
      fluid (CSF) samples. NTS were isolated from 151 (27.8%), 72 (19.8%), and 11
      (7.7%) of these positive cultures, respectively. The total 234 NTS isolates were
      serotyped: the most frequent were Salmonella enterica serotype Enteritidis (41%)
      and S. enterica serotype Typhimurium (38%). Antibiotic sensitivity testing was
      done using ampicillin (amp), chloramphenicol (chl), gentamicin (cn), co
      trimoxazole (s-t), cefuroxime (cxm), ciprofloxacin (cip), cefotaxime (ctx),
      amoxicillin-clavulanic acid 20 micrograms-10 micrograms (amc), and tobramycin
      (tob). Of the 234 isolates, 43 were sensitive to all antibiotics tested and 133
      were multiple drug resistant (MDR). The most common resistance type seen was amp,
      cn, cxm, s-t, ctx, amc, tob (36/234). Our results indicate a high proportion of
      MDR amongst the isolates from Kilifi. We conclude that 2 major serotypes of
      salmonella, i.e., S. enterica serotype Typhimurium and S. enterica serotype
      Enteritidis, of micro-epidemic nature that have been previously unrecognized in
      Kilifi are responsible for infection in Kilifi district on the coast of Kenya and
      that over half (56.8%) of total NTS isolates are MDR.

PMID- 10897372
TI  - Haptoglobin 1-1 is associated with susceptibility to severe Plasmodium falciparum
      malaria.
AB  - The haptoglobin (Hp) phenotypes were determined by polyacrylamide-gel
      electrophoresis in plasma samples obtained in 1997 from 113 Plasmodium falciparum
      malaria patients (aged 1-12 years) with strictly defined cerebral malaria, severe
      malarial anaemia, or uncomplicated malaria and 42 age-matched healthy controls
      from the same area (coastal Ghana). Hp1-1 was significantly more prevalent among
      the patients (43%) than among healthy controls (7.1%), whereas Hp2-1 and Hp2-2
      were underrepresented among the patients (11% and 2%, respectively) compared to
      the control donors (33% and 14%, respectively). No significant difference in
      frequency of Hp0 was observed between patients and controls. Among the malaria
      patients, the Hp1-1 phenotype was significantly more prevalent among patients
      with the complications of cerebral malaria and severe anaemia compared to
      patients with uncomplicated disease, whereas the reverse was seen with respect to
      Hp2-1 and Hp2-2. Our data suggest that the Hp1-1 phenotype is associated with
      susceptibility to P. falciparum malaria in general, and to the development of
      severe disease in particular.

PMID- 10897373
TI  - Tuberculin conversion after BCG vaccination: comparison by gestation and by age
      at immunization in Myanmar.

PMID- 10897374
TI  - Local and systemic concentrations of tumour necrosis factor-alpha, interleukin-6
      and interleukin-8 in bacterial osteomyelitis.
AB  - Osteomyelitis is a major cause of morbidity worldwide but there are few data
      investigating pathogenesis of infection and no investigations into local
      secretion of proinflammatory cytokines in patients. Tumour necrosis factor-alpha
      (TNF), interleukin (IL)-6 and IL-8 concentrations were measured in pus of
      infected bone from 30 Zambian patients with chronic osteomyelitis (principally
      caused by Staphylococcus aureus), in plasma, and after lipopolysaccharide
      stimulation of whole-blood leucocytes. Patients had reduced body mass index
      compared to controls (P = 0.025) and an acute-phase response. Elevated
      concentrations of proinflammatory cytokines were detected in bone compared to
      plasma (all P < 0.0002). Bone IL-8 concentrations were greater than IL-8 levels
      after lipopolysaccharide stimulation of whole blood (P < 0.01). In contrast,
      systemic and ex-vivo-stimulated concentrations of proinflammatory cytokine were
      similar in patients and controls, despite differences in body mass index and an
      acute-phase response. In summary, we observed marked local TNF, IL-6 and IL-8
      secretion in established bacterial osteomyelitis without systemic cytokine
      release.

PMID- 10897375
TI  - Central nervous system involvement in African trypanosomiasis: presence of anti
      galactocerebroside antibodies in patients' cerebrospinal fluid.

PMID- 10897376
TI  - Malaria and Salmonella infections: cause or coincidence?

PMID- 10897377
TI  - ParaSight-F test for malaria diagnosis.

PMID- 10897378
TI  - Molecular basis of clarithromycin-resistance in Mycobacterium avium
      intracellulare complex.
AB  - Nucleotide sequences of domain V and domain II regions of the 23S rRNA gene were
      determined in both in vitro-made mutants and clinical isolates of Mycobacterium
      avium and M. intracellulare conferring clarithromycin-resistance. All laboratory
      made mutants showed high level resistance to clarithromycin (> 150 micrograms ml
      1) and mutation at position 2058 (cognate with Escherichia coli base) in domain V
      region. In the clinical isolates, while the susceptible ones had no mutation in
      domain V, the resistant strains showed mutation at 2058 or 2059. Six isolates
      with low level of resistance exhibited no mutation in domain V. All strains
      tested had no mutation in domain II region. These results suggested that most of
      the resistance arose from the mutation in domain V of the 23S rRNA gene, but
      other unknown mechanisms evidently exist in mycobacteria.

PMID- 10897379
TI  - Immunization with f-Met peptides induces immune reactivity against Mycobacterium
      tuberculosis.
AB  - OBJECTIVE: To determine whether synthetic peptides containing an amino terminal
      formyl-methionine residue and corresponding to the sequence of several proteins
      produced by Mycobacterium tuberculosis, would elicit an immune response in mice.
      DESIGN: Peptides corresponding to the amino termini of 8 M. tuberculosis proteins
      and initiating with formyl methionine residues were synthesized. The ability of
      these peptides to bind to the mouse non-classical MHC class I molecule H-2M3a was
      determined by flow microfluorimetry. These peptides were used to pulse dendritic
      cells that were then injected into normal mice. These mice were subsequently
      challenged with aerosolized M. tuberculosis and, 30 days later, the number of
      viable bacteria in the lungs was determined. RESULTS: Four of the 8 synthetic
      peptides bound to H-2M3a and stabilized its expression on the cell surface.
      Injection of mice with dendritic cells pulsed with H-2M3a binding peptides
      elicited non-MHC restricted cytotoxic T lymphocytes that killed peptide pulsed
      target cells and macrophages infected with M. tuberculosis. Immunization of mice
      with syngeneic dendritic cells pulsed in vitro with 2 of these peptides led to
      retardation of the growth of M. tuberculosis following aerosol challenge.
      CONCLUSION: Peptides that bind to non-polymorphic class I molecules can elicit
      immune reactivity directed towards M. tuberculosis.

PMID- 10897380
TI  - Comparative analysis of mycobacterial infections in susceptible I/St and
      resistant A/Sn inbred mice.
AB  - SETTING: The availability and appropriate use of animal models is of significant
      importance for a better and more detailed understanding of the genetic,
      immunological and pathological mechanisms underlying the development of
      mycobacterial disease in humans. OBJECTIVE: To define a mouse model for
      tuberculosis severity that can be easily adapted to genetic and immunological
      analysis of host response to Mycobacterium tuberculosis infection. DESIGN: We
      describe here two inbred strains of mice, I/St and A/Sn (both Nramp1'), that
      differ vastly in commonly used parameters of susceptibility to infection with
      virulent and attenuated strains of M. tuberculosis. RESULTS: Following infection
      with a high dose of virulent H37Rv. M. tuberculosis and compared to their
      resistant A/Sn counterparts, I/St mice displayed more than a 2-fold shorter mean
      survival time and a more rapid onset and progression of severe body weight loss
      (cachexia). Moreover, I/St mice supported 20-100-fold higher multiplication of M.
      tuberculosis following challenge with H37Rv over a large range of infectious
      inocula. The high susceptibility of I/St mice was also reflected by more severe
      lung histopathology as evidenced by larger and more numerous lung granuloma and
      macrophage dominated cellular infiltrates. Finally, we determined that I/St are
      also unable to control infection with attenuated H37Ra M. tuberculosis and two
      strains of M. bovis (BCG and Ravenel) indicating hyper-susceptibility of the I/St
      mouse strain to mycobacterial infections. CONCLUSIONS: The results of our
      experiments suggest that comparative analysis of resistant A/Sn and susceptible
      I/St mice provides an ideal way to study host dependent aspects of tuberculosis
      susceptibility under the controlled conditions provided by an animal model.

PMID- 10897381
TI  - Kinetics of circulating antibodies, immune complex and specific antibody
      secreting cells in tuberculosis patients during 6 months of antimicrobial
      therapy.
AB  - OBJECTIVE: During the follow-up of a group of patients with active tuberculosis,
      the predictive potential of several antibody-based assays was evaluated in
      monitoring treatment efficacy. DESIGN: Eleven patients with bacteriologically
      documented pulmonary tuberculosis and two patients with tuberculosis pleurisy
      were studied over a period of 6 months, from the day before treatment to its
      completion. The kinetics of the humoral response to Mycobacterium tuberculosis
      was determined by the number of specific circulating antibody secreting cells
      (ASC) (ELISPOT assay), as well as the titres of specific circulating antibody and
      specific antibody present in circulating immune complexes (quantitative ELISA).
      RESULTS: Follow-up ELISPOT assays, performed after initiation of tuberculosis
      therapy showed a rapid increase of ASC, during the first week, followed by rapid
      3-10 fold decline of ASC in 12 of 13 patients tested. This decline occurred more
      rapidly than the mycobacterial culture conversion. In contrast, follow-up of
      ELISA assays did not give relevant information in assessing the outcome of
      treatment. CONCLUSION: In comparison with direct detection of tubercle bacilli in
      sputum samples, the rapid clearance of specific circulating ASC occurring early
      on after the onset of therapy could suggest a potential usefulness of ELISPOT in
      monitoring therapeutic response.

PMID- 10897382
TI  - Interaction of Mycobacterium tuberculosis with MH-S, an immortalized murine
      alveolar macrophage cell line: a comparison with primary murine macrophages.
AB  - We are interested in identifying a suitable model for investigating mycobacteria
      interactions with alveolar macrophages. MH-S, a murine alveolar macrophage cell
      line, is a possible candidate. OBJECTIVE: To compare the receptor mediated
      interactions of mycobacteria with primary murine macrophages and MH-S. DESIGN:
      The association of MH-S monolayers with Mycobacterium tuberculosis (MTB) and
      other defined particles was compared to that of resident Day 1 peritoneal
      macrophage (PM) and Day 4 alveolar macrophage (AM) monolayers. RESULTS: In the
      absence of serum, the association of MTB with MH-S was comparable to that of AM,
      with approximately 35% of each macrophage type binding at least one bacterium. In
      contrast, almost 80% of PM bound at least one bacterium. MTB binding was enhanced
      for all macrophage types by a heat-labile component of normal mouse serum.
      Antibodies recognising CR3 inhibited the serum-mediated enhanced binding of MTB
      by MH-S. Binding of latex, immunoglobulin coated or complement coated SRBC by MH
      S, AM and PM was comparable. Binding of zymosan by MH-S was greatly inferior to
      AM and PM. CONCLUSION: The receptor expression and particle binding properties of
      MH-S are similar to AM in many, but not all, ways. MH-S, therefore, has the
      potential to be used as a model for investigating MTB-macrophage interactions.

PMID- 10897383
TI  - Genomic mutations in the katG, inhA and aphC genes are useful for the prediction
      of isoniazid resistance in Mycobacterium tuberculosis isolates from Kwazulu
      Natal, South Africa.
AB  - Genotypic analysis of isoniazid (INH) resistance in 79 isolates of M.
      tuberculosis (MTB) was undertaken by PCR-single strand conformation polymorphism
      (SSCP), Msp1 restriction enzyme analysis and sequence analysis of specific
      regions of three genes (part of the coding sequence of katG, and promoter regions
      of the inhA operon and ahpC) in order to determine the particular allelic
      variants within these genes. The epidemiologic relatedness was determined using
      IS6110 and polymorphic G-C region (PGRS (MTB484(1)) based restriction fragment
      length polymorphism (RFLP). Mutations in katG, inhA locus and ahpC were
      identified in 77/79, 19/79 and 10/79 isolates respectively. The ability of PCR
      SSCP to detect mutations associated with INH resistance in katG, inhA and ahpC
      genes was 100% (CI 91.2-99.7%), 98.7% (CI 74.0-99.9%), and 100% (CI 69.2-100%)
      respectively. Specificity was 100%. All isolates with mutations in the 209 bp
      fragment of the MTB katG gene containing the Ser315Thr codon were positive by PCR
      RFLP using Msp1 enzyme restriction analysis. Sixteen of 19 isolates with
      alterations on the 3' end of the ribosome binding site upstream of mabA in inhA
      locus simultaneously harbored Ser315Thr mutations in KatG. In 9/10 isolates,
      mutations in the ahpC promoter region were located in the 105 bp oxyR-ahpC
      intergenic region. None of 17 INH drug susceptible isolates harbored mutations in
      any of the three genetic regions, although the katG1 allele (Arg 463 Leu) was
      present in one isolate. Characterization by IS6110/PGRS(MTB484(1))RFLP analysis
      revealed that a number of drug resistant clones are widespread in the community.
      We conclude that the frequency of the Ser315Thr katG mutation in the local strain
      population makes the PCR-RFLP MTB katG assay a reliable, rapid and useful method
      for detecting INH resistance.

PMID- 10897384
TI  - [Clinical effectiveness of magnetic field therapy--a review of the literature].
AB  - To verify the efficacy of electromagnetic fields on various diseases we conducted
      a computer-assisted search of the pertinent literature. The search was performed
      with the aid of the Medline and Embase database (1966-1998) and reference lists.
      Clinical trials with at least one control group were selected. The selection
      criteria were met by 31 clinical studies. 20 trials were designed double-blind,
      randomised and placebo-controlled. The studies were categorised by indications.
      Electromagnetic fields were applied to promote bone-healing, to treat
      osteoarthritis and inflammatory diseases of the musculoskeletal system, to
      alleviate pain, to enhance healing of ulcers and to reduce spasticity. The action
      on bone healing and pain alleviation of electromagnetic fields was confirmed in
      most of the trials. In the treatment of other disorders the results are
      contradictory. Application times varied between 15 minutes and 24 hours per day
      for three weeks up to eighteen months. There seems to be a relationship between
      longer daily application time and positive effects particular in bone-healing.
      Patients were treated with electromagnetic fields of 2 to 100 G (0.2 mT to 10 mT)
      with a frequency between 12 and 100 Hz. Optimal dosimetry for therapy with
      electromagnetic fields is yet not established.

PMID- 10897385
TI  - [Electromagnetic fields--effects on health].
AB  - This literature review shows the current knowledge of health effects on humans
      concerning static, low frequency electric and magnetic fields and high frequency
      electromagnetic fields up to 300 GHz. Basic physical knowledge and the current
      thresholds are demonstrated. Different frequency ranges of electromagnetic
      fields, their natural and technical origins and the different biological effects,
      especially possible hazards such as cancerogenity or risks for the brain, are
      discussed. Open questions and future research aspects are demonstrated. Finally
      electrosensibility and psychological aspects are shown.

PMID- 10897386
TI  - [Coronary angiography in patients over 80 years of age: indications, results,
      consequences].
AB  - Due to the continuous increase of elderly individuals in the society the
      cardiologist has to deal with elderly patients more often. The apparative
      expenditures and the invasive procedure require a critical consideration of
      benefits and risks prior to performing coronary angiography in these patients.
      The indication and frequency of coronary angiography in patients with eighty
      years or above were investigated. Furthermore, the results of angiography, the
      risks of the procedure and the therapeutic consequences were evaluated. The whole
      study population consisted of 2,500 consecutive patients (1,557 men, 943 women),
      who underwent coronary angiography at our institution from January 1st to
      November 16th in 1998. A retrospective analysis of 66 coronary angiographies (3%)
      in 61 patients (26 men, 35 women) aged 80 years or older was performed. Among
      these 61 patients, 51 were referred because of suspected coronary artery disease.
      Due to the clinical presentation a high percentage (42 patients = 82%) was
      classified as having unstable angina. 10 patients were referred due to valvular
      heart disease. Single-vessel disease was found in 14, two-vessel disease in 5 and
      multi-vessel disease in 28 patients, respectively. Percutaneous coronary
      intervention was performed in 17 patients, among these were 9 patients with multi
      vessel disease and PTCA of the culprit lesion, and 3 patients underwent bypass
      surgery. Medical therapy was decided as to 28 patients. Aortic valve replacement
      was performed in 2 of 9 patients with aortic stenosis. The clinical appearance of
      coronary artery disease in elderly patients was mostly unstable angina,
      explaining the need for intervention. Coronary angiography disclosed multi-vessel
      disease in 55% of patients. A revascularization procedure could be performed at
      least in 43% of patients with multi-vessel disease.

PMID- 10897387
TI  - [Pericardial effusion and aortitis: unusual main manifestations of giant cell
      arteritis].
AB  - Giant cell arteritis is a systemic vasculitis with segmentary vascular
      localisation, usually manifesting as temporal arteritis (Horton's disease). The
      predominant localisation in different vascular districts leads to clinical
      heterogeneity and poses a considerable diagnostic challenge. We describe a 77
      year old woman with atypical presentation of giant cell arteritis, suffering from
      fever, weight loss and fatigue, but without classical symptoms such as
      polymyalgias, arthralgias and headache. The findings of pericardial effusion and
      thickening of aortic wall in chest-CT suggested the diagnosis of giant cell
      arteritis, fully confirmed by the following biopsy and histologic examination of
      a macroscopically and palpatory normal arteria temporalis. Undergoing an
      appropriate corticosteroid-medication the patient has been free of symptoms since
      8 months.

PMID- 10897388
TI  - [Apical hypertrophic cardiomyopathy--clinical and diagnostic characteristics
      based on a case report].
AB  - Chest pain and shortness of breath are the most common symptoms of hypertrophic
      non obstructive cardiomyopathy (HCM). Accurate diagnosis of HCM and ruling out
      more common diseases such as coronary or hypertensive heart disease are important
      for the further course of the patient but can be difficult to perform with non
      invasive diagnostic tools and invasive strategies are sometimes required. We
      report on a 77-year old woman suffering from chest pain for many years. Cardiac
      catheterisation confirmed diagnosis of apical hypertrophic cardiomyopathy.

PMID- 10897389
TI  - Recurrent septicemia with lethal outcome during and after cyclosporine therapy in
      severe ulcerative colitis.
AB  - High dose corticosteroids have been the mainstay in the treatment of fulminant
      ulcerative colitis (UC) for a long time. In the last years intravenous
      cyclosporine (CyA) has been reported to be rapidly effective and relatively safe
      in patients with severe corticosteroid-resistant UC. We report on a 64 year old
      patient with a severe flare-up of UC who responded well to intravenous CyA after
      a standard therapy with high dose corticosteroids alone had been ineffective.
      However, recurrent staphylococcus aureus sepsis developed during CyA therapy.
      Despite a long-time antibiotic therapy two further episodes of staphylococcus
      aureus sepsis occurred after discontinuation of CyA treatment. Being in remission
      with his UC the patient died 14 months later of staphylococcus aureus sepsis
      despite intense antibiotic treatment. Infectious complications of this
      therapeutic regime in severe UC are known but to our knowledge a recurrent sepsis
      complicating this therapy even after cessation of CyA has not been reported in
      the literature so far.

PMID- 10897391
TI  - Three-dimensional imaging of the internal auditory canal in patients with
      acoustic neuroma.
AB  - Three-dimensional imaging of the internal auditory canal (IAC) was carried out in
      21 patients with acoustic neuromas using helical computed tomography. The IAC was
      widened in 20 patients, but no irregularities of the canal walls were seen. In
      addition, the shape of the enlarged IAC corresponded to that of the tumor on
      magnetic resonance imaging. The data suggest that widening of the IAC in acoustic
      neuroma patients is due to enlargement of the tumor. Other mechanisms, for
      example, tumor invasion or destruction caused by release of a specific mediator
      from the tumor, are unlikely to explain these findings; however, further
      investigation is needed.

PMID- 10897390
TI  - [Reciprocal modification of Fas activation and stress protein response decides
      apoptosis or resistance development of cells].
AB  - Activation of heat shock factor (HSF)-1 DNA binding and heat shock protein (hsp)
      70 expression enable resistance of cells to various forms of stress and maintain
      cell survival. Fas, a membrane-bound protein, is a central pro-apoptotic factor.
      Its activation leads to a cascade of events resulting in programmed cell death.
      Herein, these two mechanisms with contrary functions, promoting either cell
      survival or death, were addressed for their potential to inhibit each other's
      activation. Induction of Fas-mediated signalling was followed by a rapid decrease
      of HSF1 DNA binding and inducible hsp70 expression. Inhibition of HSF1 DNA
      binding was demonstrated to be based on absent hyperphosphorylation of HSF1
      during FAS-signalling. These effects of Fas-activation on the HSF1/hsp70 stress
      response were blocked by ICE (caspase 1)-inhibitors, suggesting an ICE-mediated
      process. Furthermore, inhibition of HSF1/hsp70 was accompanied by an increase of
      apoptosis rates from 20% to 50% in response to heat stress. When analyzing Fas
      mediated apoptosis in the presence of HSF1/hsp70 activation, decreased apoptosis
      rates were detected with induced expression of hsp70 but not with activation of
      HSF1-DNA binding alone. Thus, we conclude that inhibition of the HSF1/hsp70
      stress response during Fas-mediated apoptosis and vice versa may facilitate a
      cell to pass a previously chosen pathway, stress resistance or apoptosis.

PMID- 10897392
TI  - Relationship between cystic change and rotatory vertigo in patients with acoustic
      neuroma.
AB  - Acoustic neuromas are benign neoplasms that most often arise from the vestibular
      nerve. Many patients with this tumor experience some degree of vestibular
      symptoms. However, patients rarely complain of rotatory vertigo. Acoustic
      neuromas are known to exhibit a cystic appearance in some patients. It was
      hypothesized that cystic change might be a causative factor for rotatory vertigo.
      A retrospective study of 178 patients with unilateral acoustic neuroma who
      underwent surgery in the Department of Otolaryngology at Tokyo Medical and Dental
      University was carried out. The cystic appearance of the tumors was detected
      preoperatively by magnetic resonance imaging and confirmed at surgery. The
      relationship between cystic change of the tumor and presentation with rotatory
      vertigo was examined. Of the 178 patients studied, only 10 had both cystic change
      of the tumor and rotatory vertigo, and 120 had neither cystic tumor nor rotatory
      vertigo. Of the remaining 48 patients, 24 experienced rotatory vertigo with
      negative findings for cystic tumor and the other 24 had evidence of cystic tumor
      but no rotatory vertigo. Tumor with cystic change was observed in 34 patients,
      accounting for 19.1% of all patients studied. Rotatory vertigo was also
      experienced in 34 patients (19.1%). Of the 34 patients with cystic lesions, 29.4%
      (10) had rotatory vertigo. The difference in percentage of the two groups did not
      reach statistical significance. It is suggested that there may be other factors
      causing rotatory vertigo in patients with acoustic neuromas than cystic change of
      the tumor.

PMID- 10897393
TI  - Contrast-enhanced magnetic resonance imaging of the cranial nerves in patients
      with acoustic schwannoma: correlation with surgical findings.
AB  - Eighteen patients with acoustic schwannoma were examined on a 1.5-T magnetic
      resonance imaging (MRI) unit with precontrast and postcontrast T1-weighted spin
      echo sequences. Each abnormality was assessed in terms of the size, location,
      extensions and signal intensity of the lesions. If a nerve was enhanced and was
      involved by the tumor around the fundus of the internal auditory canal (IAC), the
      nerve was interpreted to be the originating nerve. The postcontrast T1-weighted
      images revealed enhanced masses of the cerebellopontine angle and/or the IAC in
      all cases. In 11 of the 19 operated patients with shwannomas, the site of tumor
      origin (or origin nerve) was confirmed by surgery. In 2 of the 11 cases (18%),
      surgical findings coincided with the T1-weighted image findings. Facial nerve
      enhancement on the ipsilateral side of the tumor was noted in 10 cases (53%) and
      the contralateral facial nerve enhancement was demonstrated in 7 (70%). The
      enhancement of facial nerve associated with acoustic schwannoma was not
      correlated to the degree of nerve compression by the tumor. These results
      demonstrate that it was possible, although infrequent, to predict the site of
      origin of acoustic schwannoma before surgery in some patients. Improvement of the
      imaging matrix or multiplanar reconstruction techniques with three-dimensional
      data acquisition may make it possible to overcome the limitations of MRI.

PMID- 10897394
TI  - Positron emission tomographic imaging of acoustic neuromas.
AB  - Positron emission tomography (PET) examination with both [11C]methyl-l-methionine
      (Met) and [18F]fluoro-2-deoxyglucose (FDG) was performed in the same patients
      with acoustic neuroma wherever possible in order to compare the usefulness of the
      two methods. The study included six patients who visited the Osaka City
      University Hospitals, between April 1994 and October 1998, for complaints
      associated with acoustic neuroma. All patients were examined by magnetic
      resonance imaging (MRI) and Met-PET. Four patients were examined by FDG-PET. The
      tumor's region of highest accumulation was selected as the region of interest;
      the tumor/normal ratio (T/N ratio) was defined as the ratio of radioisotope
      counts for tumor and normal gray matter. All tumors in this series were detected
      by MRI. In the Met-PET images, four tumors were easily identified, with a high
      T/N ratio. However, two tumors could not be identified using Met-PET. On FDG-PET,
      no cases could be identified. The T/N ratio for the four patients with positive
      Met-PET findings averaged 1.694 +/- 0.266. PET, especially Met-PET, is a powerful
      means of examination providing functional information on tumors in acoustic
      neuroma. Met-PET may therefore be useful for acoustic neuroma, which is known to
      proliferate slowly, as for malignant tumors, in evaluating the proliferating
      potential of a tumor, in determining patients in whom to perform radiological
      treatment and in monitoring post-treatment progress.

PMID- 10897396
TI  - Sudden-onset tinnitus associated with arterial dissection of the vertebrobasilar
      system.
AB  - Magnetic resonance (MR) images of 62 patients with tinnitus were reviewed. These
      included T1-weighted and T2-weighted axial images and three-dimensional spoiled
      gradient-recalled acquisition in steady-state (3D-SPGR) imaging with
      gadopentetate dimeglumine. In 49 cases with tinnitus occurring gradually, the MR
      images of 2 cases (4.1%) suggested arterial dissection of the vertebrobasilar
      system. One of these patients underwent vertebral angiography (VAG) and no
      dissection was confirmed. In 13 cases of sudden-onset tinnitus, MR images of 3
      cases (23.1%) suggested arterial dissection. Of these three cases, VAG was
      performed in two, resulting in arterial dissections being confirmed in two cases.
      It was concluded that the arterial dissection of the vertebrobasilar system was
      one of the causes of sudden-onset tinnitus. Abnormalities in neurotological
      examinations in cases with tinnitus caused by the arterial dissection of
      vertebrobasilar system implied that the tinnitus was caused by inner ear
      dysfunction.

PMID- 10897395
TI  - Evaluation of the vestibular aqueduct in vestibulocochlear disorders by magnetic
      resonance imaging.
AB  - The visibility of the vestibular aqueduct (VA) was examined using magnetic
      resonance imaging (MRI) in 95 patients: 15 patients with Meniere's disease, 4
      with vestibular Meniere's disease, 4 with cochlear Meniere's disease and 72
      patients with other vestibular and/or cochlear disorders. In order to visualize
      the VA, the T2-weighted image (T2WI) and the proton-density weighted image (PDWI)
      were obtained in the sagittal plane with a head coil. The visibility of the VA
      was classified into 4 grades, i.e. grade 0 (not visible), grade 1 (partially
      visible with PDWI), grade 2 (partially visible with T2WI) and grade 3 (clearly
      visible with T2WI). The visibility of the VA was significantly lower bilaterally
      in Meniere's disease, vestibular Meniere's disease, cochlear Meniere's disease
      and idiopathic bilateral sensorineural hearing loss (IBSNHL) than in the other
      diseases. The differences among Meniere's disease, vestibular Meniere's disease
      and cochlear Meniere's disease were not significant. The significance of
      decreased visibility in IBSNHL is unknown so far. The VA studies using MRI
      strongly suggest that the pathogenesis of Meniere's disease, vestibular Meniere's
      disease, cochlear Meniere's disease and IBSNHL is, at least in part, related to
      the findings of the VA.

PMID- 10897397
TI  - Evaluation of radiological examination for sensorineural hearing loss.
AB  - The accuracy of radiological examinations has improved and their diagnostic
      ability has markedly increased. However, the cost of such examinations has also
      recently become an issue. In this study, the clinical significance of
      radiological examinations for sensorineural hearing loss (SNHL) was evaluated and
      the value of their utilization was reconsidered. A total of 1,276 ears of 724
      patients who demonstrated unilateral or bilateral SNHL was studied
      retrospectively. Findings of radiological examinations such as plain X-ray (X-p),
      computed tomography (CT) and magnetic resonance imaging (MRI) of the brain or the
      temporal bone were investigated. Temporal bone X-p was usually performed to rule
      out acoustic tumors (AT). CT was further performed in 119 patients (16.4%) and
      MRI in 84 patients (11.6%) in total. The reasons or symptoms for further
      examination such as CT or MRI were X-p findings or auditory symptoms suspicious
      for AT or vertigo/dizziness suspicious for intracranial disease. Of five causes
      with AT, two with a small tumor exhibited normal findings for the internal
      auditory canal on temporal bone X-p. These small ATs were finally confirmed by
      MRI. MRI could also detect lacunar infarctions, cerebral atrophy and high jugular
      bulb which might be related to SNHL. These findings confirmed that MRI is very
      useful for detecting small ATs and suggested that MRI also reveals cerebral
      vascular insufficiency in patients with SNHL.

PMID- 10897398
TI  - Consecutive imaging of the facial nerve using high-resolution magnetic resonance
      imaging.
AB  - This study examined the signal intensity of the facial nerve on T1-weighted
      images using the multiplanar reconstruction (MPR) method of the high-resolution
      magnetic resonance imaging technique. The facial nerves of 12 sides in 6 normal
      adults were consecutively observed from the mastoid area to the intraparotid
      area. Results indicated that facial nerves showed similar or relatively high
      signal intensity compared with the intensity of the parotid parenchyma. Although
      previous studies have indicated that the intraparotid facial nerve had a low
      signal intensity, facial nerves were probably confused with the intraparotid
      ductal system or vessels which show low signal intensity on T1-weighted images or
      with low signal lines due to chemical artifacts. All facial nerve trunks were
      clearly identified; however, 33% (4/12) of second branches of the nerves shifted
      or curved too strongly to be detected in the parotid parenchyma with this method.

PMID- 10897399
TI  - High-resolution computed tomography using multiplanar reconstruction for the
      facial nerve canal.
AB  - Multiplanar reconstruction (MPR) images along the facial nerve canal were
      prepared with high-resolution computed tomography (HRCT) and their clinical
      usefulness was evaluated. Over a period of 6 years, temporal bone HRCT was
      performed on 628 cases. Of these cases, 6 patients exhibited facial nerve
      lesions, including facial nerve schwannoma (n = 3), traumatic facial nerve palsy
      (n = 2) and congenital facial nerve palsy (n = 1). Thirty patients without facial
      nerve lesions, such as chronic otitis media, were randomly selected as controls.
      Two types of MPR image were composed. One was along the labyrinthine and tympanic
      segment, and the other was along the tympanic and mastoid segment. Other MPR
      images, such as those along the facial nerve canal and bone fracture line, were
      composed as needed. All MPR images were prepared with real-time observation of
      delicate angles. In all cases, MPR images delineated the labyrinthine and
      tympanic segment in one image, and the tympanic and mastoid segment in another
      image. In two patients with traumatic facial nerve palsy, the MPR images revealed
      a relationship between the facial nerve canal and the bone fracture. In
      conclusion, MPR images of the facial nerve canal are easy to obtain and are
      useful in detecting facial nerve schwannoma, traumatic facial nerve palsy and
      congenital facial nerve palsy.

PMID- 10897400
TI  - Identification of the intraparotid facial nerve on magnetic resonance imaging.
AB  - As a result of recent advances in magnetic resonance imaging (MRI) technology,
      direct imaging of the intraparotid facial nerve has become possible. The
      usefulness of MRI is well known in the diagnosis of parotid tumors. Using a 0.5 T
      midfield MR unit, this study aimed to visualize the intraparotid facial nerve in
      5 normal volunteers and 14 patients with parotid tumors (on 24 normal sides and
      14 affected sides). Under appropriate conditions for MRI, the facial nerve was
      detectable on 9 out of 10 affected sides and 17 out of 20 normal sides. The
      running course of the facial nerve was consistent with MRI findings in five
      patients who underwent surgery. The imaging conditions suitable for visualizing
      the intraparotid facial nerve are reported and the usefulness of MRI in the
      diagnosis of parotid tumors is discussed.

PMID- 10897401
TI  - Usefulness of high-resolution magnetic resonance cisternography in patients with
      hemifacial spasm.
AB  - To analyse the usefulness of preoperative magnetic resonance (MR) cisternography
      in patients with hemifacial spasm (HFS), MR observations were compared with
      surgical findings. High-definition images were obtained using MR cisternography
      which employed a long echo train length, fast spin-echo sequence, which revealed
      both nerves and blood vessels without any contrast media. In 35 HFS patients,
      certified radiologists examined the presence of vascular compression of the
      facial nerve and identified the offending vessels. MR cisternography depicted
      neurovascular compression in 31 patients (sensitivity 88.6%) and correctly
      determined the offending vessels in 28 patients. In 4 patients, MR cisternography
      revealed the presence of the vessel near the facial nerve, but the radiologist
      evaluated the compression as questionable (false-negative rate 11.4%). Even in
      these patients, MR cisternography revealed the precise anatomy of
      cerebellopontine (CP) cistern. High-resolution MR cisternography is useful in
      identifying the vessels and nerve bundles in the CP cistern, and in so doing can
      provide surgeons with valuable information regarding neurovascular decompression
      for HFS.

PMID- 10897402
TI  - Magnetic resonance imaging findings in a patient with bilateral facial paralysis
      due to malignant lymphoma.
AB  - In malignant lymphomas, especially non-Hodgkin's lymphomas, invasion to the
      central nervous system (CNS) often occurs. A patient is reported here with
      bilateral facial paralysis due to invasion of a malignant lymphoma to the CNS.
      Contrast magnetic resonance imaging (MRI) revealed swelling of the entire length
      internal auditory meatus and enhancement in the entire length of the facial
      nerve. Transcranial magnetic stimulation and MRI revealed that later facial nerve
      injury was present before the onset of paralysis due to a malignant lymphoma.
      Therefore treatment should be performed with consideration given to the possible
      invasion of the tumor to the CNS.

PMID- 10897403
TI  - Inner ear anomaly of three-dimensional computed tomography: computed tomographic
      attenuation and image changes.
AB  - With regard to image diagnosis of inner ear anomalies, three-dimensional computed
      tomography (3D-CT) is useful in obtaining very realistic images that are
      unmatched by 2D-CT. Unlike the step scanning in the existing 2D-CT, in helical 3D
      CT, scanning is performed in a spiral motion by continuously rotating the scanner
      and moving the table along the body axis at a constant speed. As a result, data
      obtained by this CT are continuous and very smooth curves can be obtained. Among
      the data, the CT attenuation determines the quality of the final 3D images. In
      the present paper, the usefulness of 3D-CT was investigated in a case with
      Mondini-type inner ear malformation.

PMID- 10897404
TI  - Three-dimensional magnetic resonance imaging findings of inner ear anomaly.
AB  - Using three-dimensional magnetic resonance imaging (3D-MRI), the membranous
      labyrinth was examined in normal cases and in a case with bilateral Mondini-type
      inner ear malformations. Both ears were also examined by high-resolution computed
      tomography (CT) of the temporal bone. 3D-MRI provided more detail than findings
      obtained by conventional high-resolution CT and it enabled 3D observations to be
      made. Detailed examination of maximum intensity projection images along the
      cochlea axis revealed the cochlear turns in three dimensions.

PMID- 10897405
TI  - Mannose receptor and scavenger receptor: two macrophage pattern recognition
      receptors with diverse functions in tissue homeostasis and host defense.
AB  - In this report we have reviewed our recent data which suggest a new function for
      MR in antigen delivery in lymphoid organs, together with highlighting three
      recent discoveries from our laboratory concerning the role of SR-A in adhesion,
      phagocytosis of apoptotic cells and protection from endotoxic shock in mice. The
      diversity of functions mediated by each receptor demonstrates there is much yet
      to be discovered about how macrophages use their cell surface receptors to 'see'
      the external environment, and yet perform a wide range of strictly regulated
      functions.

PMID- 10897406
TI  - Complement receptor 3 (CR3): a public transducer of innate immunity signals in
      macrophages.

PMID- 10897407
TI  - The role of C-type lectins in the innate immunity against pulmonary pathogens.

PMID- 10897408
TI  - Modulation of nitric oxide production by lung surfactant in alveolar macrophages.

PMID- 10897409
TI  - Development of chimeric collectins with enhanced activity against influenza A
      virus.

PMID- 10897410
TI  - Initial steps in Streptococcus pneumoniae interaction with and pathogenicity to
      the host.
AB  - Streptococcus pneumoniae (Pnc) is one of the leading pathogens in the world.
      Attachment to respiratory mucosal and lung surfaces is presumed to be involved in
      carriage, in disease and in the interaction with macrophages initiating innate
      immune responses. We hypothesized that bacterial adhesins mediate Pnc adhesion
      and host cell invasiveness. Initial studies have focused on the purification of
      cell wall and membrane proteins using fetuin affinity chromatography, SDS PAGE
      and western blot analysis probed with pooled healthy human sera. Using a Pnc
      clinical isolate, and a gpt mutant we have detected 10-lectin proteins isolated
      from the cell wall and adherent to the affinity column and 15 lectins isolated
      from membrane extracts. The fetuin-captured lectins agglutinated rabbit
      erythrocytes. 15 proteins in the cell wall and 18 proteins in the membrane that
      failed to bind to the fetuin column did not agglutinate rabbit erythrocytes.
      Further purification of the cell wall and membrane fetuin-separated fractions was
      achieved via anion exchange FPLC, was verified by SDS PAGE. These proteins
      maintained their agglutinating activity, and were subsequently tested for their
      ability to interfere with Pnc adhesion and invasion of epithelial cells in
      culture. Additional biochemical, immunological and molecular techniques are being
      used in attempt to identify relevant proteins.

PMID- 10897411
TI  - Role of cytokines in the maturation and function of macrophages. Effect of GM-CSF
      and IL-4.

PMID- 10897412
TI  - Mast cell modulation of the innate immune response to enterobacterial infection.

PMID- 10897413
TI  - The NADPH oxidase diaphorase activity in permeabilized human neutrophils and
      granulocytic like PLB-985 cells.
AB  - The phagocyte NADPH oxidase is a multicomponent transport chain that generates
      superoxide, a precursor of microbicidal oxidants, important for host defense.
      This transport chain is contained mainly in the large membrane subunit of the
      oxidase (gp91phox), and transfers electrons from cytosolic NADPH, through FAD
      binding and heme centers, to molecular oxygen (Babior, 1999; Fujii and Kakinuma,
      1991; Rotrosen et al., 1992; Segal and Abo, 1993). Cross et al. have recently
      described a novel NADPH oxidase diaphorase activity present in the membrane
      fraction of activated neutrophils, using a cell free model (Cross et al., 1994).
      This diaphorase activity is measured by the artificial electron acceptor 4
      iodonitrotetrazolium violet (INT) and is attributed to the reduction of the
      flavin center of the flavocytochrome (Cross et al., 1994; Li and Guillory, 1997).
      In the present study we establish a system for detecting diaphorase activity in
      intact cells. Neutrophils and PLB-985 cells, that were differentiated using 1.25%
      dimethyl sulfoxide (DMSO) to granulocyte phenotype, were permeabilized by
      electroporation, and diaphorase activity was determined using INT. Neutrophils
      and differentiated PLB-985 cells stimulated by PMA or GTP gamma S showed a
      diaphorase activity that was not present in unstimulated differentiated cells.
      The diaphorase activity could not be detected in undifferentiated cells and was
      developed during differentiation. The pattern of diaphorase activity in
      stimulated parent differentiated PLB cells was similar to that observed in
      stimulated human neutrophils. The permeabilized-INT cell system offers a unique
      tool for the evaluation of NADPH oxidase diaphorase activity, in whole cells.

PMID- 10897414
TI  - Activation of cytosolic phospholipase A2 by opsonized zymosan in human
      neutrophils requires both ERK and p38 MAP-kinase.
AB  - The present study demonstrates that stimulation of human neutrophils with
      opsonized zymosan (OZ), which binds to Fc gamma receptors (Fc gamma Rs) and C3b
      receptors, activates both ERK and p38 MAP-kinase. Thus, the relative role of both
      types of MAP-kinase, ERK and p38, in activation of cPLA2 by OZ was studied. cPLA2
      activation by OZ was detected 15 sec after stimulation, maintained a plateau for
      10 min and decreased thereafter. p38 MAP-kinase activation exhibited kinetics
      similar to that of cPLA2, while ERK activation was detected within 15 sec but
      decreased significantly in less than 5 min after stimulation. Pretreatment of the
      cells with the MEK inhibitor, PD-098059, or the p38 MAP-kinase inhibitor, SB
      203580 resulted in total inhibition of ERK or p38 MAP-kinase activity,
      respectively. Each inhibitor caused a partial inhibition during the time course
      of cPLA2 activity, while their combination caused a total inhibition. Compared to
      OZ, inactivated OZ, which does not contain the complement proteins, induced an
      identical time-dependent stimulation of ERK and p38 MAP-kinase as well as a
      similar cPLA2 activity, suggesting that the role of the C3b receptors in this
      system is negligible. It is concluded that OZ activates both ERK and p38 MAP
      kinase and that the two isotypes are required for the onset and maintenance of
      cPLA2 activity.

PMID- 10897415
TI  - Cytosolic phospholipase A2 is required for the activation of the NADPH oxidase
      associated H+ channel in phagocyte-like cells.
AB  - The NADPH oxidase producing-superoxide is the major mechanism by which phagocytes
      kill invading pathogens. The human myeloid cell line PLB-985 was transfected to
      express p85 cytosolic phospholipase A2 (cPLA2) antisense mRNA and stable clones
      were selected which lack detectable cPLA2. cPLA2-deficient PLB-985 cells
      differentiate similarly to control PLB-985 cells in response to retinoic acid,
      DMSO or 1,25 dihydroxyvitamin D3 indicating that cPLA2 is not involved in the
      differentiation process. Despite the normal synthesis of NADPH oxidase subunits
      during differentiation of cPLA2-deficient PLB-985 cells, these cells fail to
      activate NADPH oxidase in response to a variety of soluble and particulate
      stimuli, but addition of exogenous arachidonic acid (AA) fully restores oxidase
      activity. This establishes an essential requirement of cPLA2 generated AA for
      activation of phagocyte NADPH oxidase. In order to elucidate the mechanism by
      which cPLA2 regulates the oxidase, the role of cPLA2 in NADPH oxidase associated
      H+ channel was studied. Activation of differentiated PLB cells resulted in a Zn+2
      sensitive alkalization, indicating H+ channel activity. In contrast,
      differentiated PLB-D cells failed to activate the H+ channel, but addition of
      exogenous AA fully restored this activity, indicating an essential and specific
      physiological requirement of cPLA2-generated AA for activation of the H+ channel.
      The presence of the H+ channel inhibitor, Zn+2, caused significant inhibition of
      NADPH oxidase activity, suggesting a role of the NADPH oxidase associated H+
      channel in regulating oxidase activity.

PMID- 10897416
TI  - The role of NK cells in innate immunity.

PMID- 10897417
TI  - Similarities and dissimilarities between humans and mice looking at adhesion
      molecules defects.

PMID- 10897418
TI  - The role of dendritic cells at the early stages of Leishmania infection.

PMID- 10897419
TI  - DNA-based vaccines: role of dendritic cells in antigen presentation.

PMID- 10897420
TI  - Distinct patterns of IL-1 alpha and IL-1 beta organ distribution--a possible
      basis for organ mechanisms of innate immunity.

PMID- 10897422
TI  - Structure activity relationship study of polymyxin B nonapeptide.

PMID- 10897423
TI  - The clinical significance of neutrophil dysfunction.

PMID- 10897421
TI  - Structure and biology of cathelicidins.

PMID- 10897424
TI  - Clinical significance of functional aberrations in macrophage and NK cells, in
      type-1 cytokines and in lectin-binding molecules.

PMID- 10897425
TI  - Klebsiella infections in the immunocompromised host.

PMID- 10897426
TI  - Macrophage-recognized molecules of apoptotic cells are expressed at higher levels
      in AKR lymphoma of aged as compared to young mice.
AB  - While a direct relation between aging and tumorigenesis is well established, a
      slower tumor progression rate was reported in old as compared to young cancer
      patients. The mechanisms responsible for the less aggressive behavior of tumors
      in the aged, are largely unknown. We have recently shown an increase in apoptotic
      cell death in tumors derived from aged as compared to young animals in the AKR
      lymphoma. This was shown by DNA flow cytometry and by the ladder type DNA
      fragmentation in agarose gel electrophoresis. Analysis of the expression of genes
      involved in apoptosis in tumors derived from young and old animals showed a lower
      bcl-2 expression in those from the aged. The Fas antigen, on the contrary,
      displayed higher expression levels on lymphoma cells derived from old than on
      those from young mice. Apoptotic cells are recognized and phagocytosed mainly by
      macrophages. One molecular property of apoptotic cells which is recognized by
      macrophages is a loss in cell surface sialic acid concomitantly uncovering
      galactose residues. While comparing the "eat me status" phenotype of the tumor
      cells derived from young and aged animals, by the use of lectins recognizing
      sialic acid and galactose residues, FACS analysis showed a decrease in cell
      surface sialic acid and a gain in galactose residues in aged as compared to young
      mice. Moreover, Western blot analysis showed that a 130 Kda sialylated membrane
      glycoprotein was expressed at a lower level in tumors from the old as compared to
      young mice. Our results, at both the cellular and molecular levels, particularly
      with regard to molecules recognized by macrophages, indicate that increased
      apoptotic cell death in tumors from old as compared to those from young animals
      constitutes, as we have previously suggested, one of the mechanisms of the age
      related decrease in tumor progression rate.

PMID- 10897427
TI  - Sensitivity to macrophages decreases with tumor progression in the AKR lymphoma.
AB  - Resistance to immune reactions, innate or acquired, may be one of the mechanisms
      responsible for the progression of tumors. We have, indeed shown higher numbers
      of macrophages surrounding low- as compared to high-malignancy cells. In the
      present study we examined the level of cell surface molecules known to determine
      sensitivity to macrophages, namely galactose (GAL) and sialic acid (SA) residues.
      A histochemical assay for identification of SA by electron microscopy showed a
      higher cell surface content on metastatic (MT) than on primary (PT) tumor cells.
      The FACS data seen with fluorescent lectins showed a higher binding of Sambucus
      nigra agglutinin, which identifies SA attached to terminal GAL in -2.6 or -2.3
      linkage, in MT than in PT cells. Binding of Maakia amurensis lectin (MAL-1),
      which identifies SA at position 3 of GAL, showed that the MT cells contain two
      subpopulations, one binding more MAL-1 and another less. Cell sorting showed a
      more aggressive behavior of the first population. The comparison of Peanut
      agglutinin (PNA) binding, which identifies GAL, demonstrated a decreased amount
      of PNA receptors in MT as compared to PT cells. Western blot analysis of the
      membranal proteins with different lectins, identified 3 sialylated glycoproteins.
      The 88 kDa glycoprotein had no significance for metastatic potential. The 130 kDa
      glycoprotein was higher in MT than on PT cells. The 220 kDa glycoprotein was
      practically present only on MT cells. The tendency observed was of a higher level
      of membranal glycoconjugates terminally sialylated with subterminal galactose
      residues, inMT cells as compared to PT cells. This may explain the recently found
      decrease in apoptotic cell death with increasing aggressiveness of the AKR
      lymphoma and suggests a lower sensitivity to macrophages with tumor progression.
      Treatment based on the reduction in sialic acid content might render the tumor
      cells more vulnerable to macrophages. We found, indeed, that Wheat germ
      agglutinin (WGA) injected in vivo, exerted an inhibitory effect on growth of the
      lymphoma. We found moreover that WGA-treated tumor cells were more sensitive than
      nontreated cells to macrophages in vitro.

PMID- 10897428
TI  - Opposing effects of IL-1 alpha and IL-1 beta on malignancy patterns. Tumor cell
      associated IL-1 alpha potentiates anti-tumor immune responses and tumor
      regression, whereas IL-1 beta potentiates invasiveness.

PMID- 10897429
TI  - [Hereditary diseases in pathologoanatomy practice].
AB  - This paper is a review of pathological aspects of hereditary diseases. High
      significance of mutations in lethal effects of human reproduction is shown,
      especially in miscarriages and infant death. The importance of genetic approaches
      for the pathologist's practice is emphasized. Current pathology diagnosis of
      hereditary diseases includes autopsy, biopsy, histological, histochemical,
      electron microscopic, cytogenetic, molecular genetic tests. Geneticists and
      pathologists should work together in the directions: analysis of clinical
      mistakes, study of pathogenesis, etiopathogenic nosology of the diseases,
      development of new diagnostic methods.

PMID- 10897430
TI  - [Bronchoalveolar neoplasms].
AB  - This review concerns the development and progression of one of the forms of
      peripheral lung cancer--bronchiolo-alveolar carcinoma (BAC). The study is based
      on the comparison of roentgenological, histological, immunohistochemical
      examinations and results of surgical treatment of 482 patients with this tumor.
      Morphological and clinical variants of BAC are defined. It is confirmed that
      their biological behavior may vary within the forms and differ from common
      adenocarcinoma. A close correlation exists between clinicoroentgenological
      picture and histological form of BAC.

PMID- 10897431
TI  - [Morphologic and molecular-genetic characteristics of keratinization and
      apoptosis in squamous cell lung carcinoma].
AB  - 46 samples of squamous-cell lung carcinoma (SqCLC) from surgical patients were
      examined for biomolecular tumor markers (pancytokeratins, c-myc, p53, bcl-2, Bax,
      Ki-67, IGF-system) and apoptosis. Keratinization appeared an independent from
      apoptosis type of programmed cell death. It relates to cell death by
      differentiation, is followed by accumulation of c-fos, c-myc, Bax, IGF-II, IGFBP
      2, IGFBP-5 this indicating their involvement in the regulation of this process.
      High level of apoptosis does not determine positive prognosis of the neoplastic
      process as it is not a single variant of programmed cell death in SqCLC.
      Malignant grade of SqCLC depends upon correlation between the proliferative
      processes and various types of cell death. Better prognosis of well and
      moderately differentiated SqCLC (as compared to poorly differentiated carcinomas)
      may be due to the fact that high proliferative activity of the tumor cells is
      balanced by their death by keratinization.

PMID- 10897432
TI  - [Atypical adenomatous hyperplasia of the lung].
AB  - Clinicomorphological analysis was performed in 12 cases of atypical adenomatous
      hyperplasia of the lung (AAH). This is the proliferative lesion consisting of
      atypical epithelial cells along the alveolar septa which are found incidentally
      during pathologic examination of the lung resected because of cancer. We studied
      morphological and biological characteristics of AAH cells including
      cytodifferentiation, proliferative activity, tumor-suppressor genes. Our review
      of the studies of AAH revealed that AAH is alveolar intraepithelial dysplasia and
      a precursor of lung adenocarcinoma. AAH is an important lesion corresponding to a
      step in carcinogenesis for peripheral lung adenocarcinomas.

PMID- 10897433
TI  - [Rapid progression of passaged mouse hepatocarcinoma associated with the loss of
      cell polarity].
AB  - Two transplantable differentiated mouse hepatocarcinomas were obtained in B6 D2
      F1 mice from primary tumors induced by initiation (NDEA)-promotion
      (phenobarbital) protocol. Both HC were slowly growing with time from passage to
      passage of 5-7 months (s-HC). A fast-growing variant with time between passages
      of 2-3 weeks appeared in one mouse on the third passage (f-HC). The three HC
      strains constantly retained their phenotype. The s-HCs were characterized by
      prominent cell polarity according to organization of the cytoskeleton and
      distribution of domain-specific membrane-associated markers. Cell polarity was
      completely destroyed in the fast-growing variant. Cell adhesion in the latter
      tumor was very low. An in vitro growing strain of f-HC was easily obtained
      enabling experimental study of regulation of progression in HCs.

PMID- 10897434
TI  - [Specific characteristics of skin basal cell carcinoma invasion].
AB  - Histological, electron-microscopic and immunomorphologic studies were made in 30
      cases of basal cell carcinoma (BCC) of the skin. In the immunomorphological study
      the antibodies to pankeratin, to keratins of N8, 17 (K N8, K N17) and to laminin
      were used. Two microscopical types of BCC growth distinguished by their clinical
      manifestations were revealed: compact-nodulous and diffuse-infiltrative. In BCC
      with diffuse-infiltrative type of growth the basement membrane was markedly
      fragmentated or completely absent in some regions. This indicates aggressive
      character of these tumors. This type of BCC growth was characterized by
      pronounced expression of K N8. The expression of K N17 was revealed in all BCCs.

PMID- 10897435
TI  - [Structural organization of sigmoid and rectum wall in patients with cancer after
      use of enterosorbent with adsorbed metronidazole].
AB  - Preoperative preparation with enterosorbent SUMS-1 followed by lavage improves
      microcirculation in the colon wall and decreases issue of toxins and antigens
      from the colon lumen as compared to lavage alone. Oral use of the sorbents in the
      presurgical period in patients with colon carcinoma allows to protect lymphatic
      and blood system from excessive resorption of toxins, bacteria and metabolites
      and rapidly decrease the degree of the inflammation in the wall of the organ.

PMID- 10897436
TI  - [Chronic viral hepatitis and alcoholic liver: clinico-morphological
      correlations].
AB  - 69 patients with alcohol addiction infected with hepatitis viruses underwent
      clinical, laboratory and morphological examinations using light and electron
      microscopic studies of liver biopsies. Light microscopy revealed three variants
      of liver damage: viral, alcoholic and mixed. Both etiological factors affect
      manifestations and course of the disease as shown by electron microscopy in spite
      of morphological signs of only viral or mixed lesion. The lowest index of
      histological activity is found in combination alcohol + HCV, the highest index
      being in patients with HBV + HCV and HBV + HDV. Alcohol abuse in combination with
      HCV infection increases histological activity of liver damage.

PMID- 10897437
TI  - [Spindle-cell variant of thyroid medullary carcinoma with favourable prognosis].
AB  - A case of a favourable outcome of spindle-cell medullary carcinoma of the thyroid
      is reported. Electron-microscopically, there was no correlation between
      histological and ultrastructural differentiation. The tumor consisted mainly of
      ultrastructurally differentiated cells with endocrine granules which may be the
      cause of the favourable prognosis.

PMID- 10897438
TI  - [A rare complication after surgical correction of the rupture of Valsalva's sinus
      aneurysm into the right heart ventricle].
AB  - Postsurgical myocardial infarction in a 68-year-old female was observed after
      occasional compression of the coronary artery by a teflon gasket when P-like
      suture was applied on the anterior wall of the right ventricle in the course of
      surgical intervention for closure of the aortic-right-ventricular fistula. The
      latter had formed after the rupture of Valsalva's sinus aneurysm into the right
      ventricle this being the cause of the surgery. The authors propose how to
      document the diagnosis and medical death certificate in similar cases.

PMID- 10897439
TI  - [Pulmonary microembolism with particles of synthetic polymer "Polysorb"in the
      treatment of postpartum endometritis].
AB  - A case of fatal massive pulmonary microembolism with particles of the synthetic
      polymer preparation in a female of 26 early after delivery is reported. The case
      is interpreted as a maternal death of the 1st group due to occasional damage in
      the process of uterine cavity washing with a suspension of a synthetic polymer
      preparation polysorb in the treatment of purulent postpartum endometritis.

PMID- 10897440
TI  - [Chronic endometritis].
AB  - The author reviews literature data on the incidence, etiology and morphological
      diagnosis of chronic endometritis, analyses information on differences in cell
      composition of the endometrium in normal conditions and in chronic inflammation,
      focuses on alterations in systemic and local immunological parameters in chronic
      inflammation and chronic endometritis, in particular.

PMID- 10897441
TI  - [Report from the II Congress of the International Union of Pathologists
      Associations].

PMID- 10897442
TI  - [The 17-th European Pathologists Congress, September 18-23, 1999, Barcelona].

PMID- 10897444
TI  - [In Process Citation]

PMID- 10897443
TI  - [The 3-rd All-Russia Methodological Conference on teaching of pathological
      anatomy].

PMID- 10897445
TI  - Tailflick escape behavior in larval and juvenile lobsters (Homarus americanus)
      and crayfish (Cherax destructor).
AB  - We examined the escape behavior of larvae and postlarvae of the American lobster
      (Homarus americanus) and of adult immature (stage ADI) crayfish (Cherax
      destructor). Responses to standardized water jet stimuli delivered through a
      pipette were observed and analyzed. Lobster larvae did not respond to stimuli
      within 60 ms, indicating that they do not have functional giant fibers. The first
      movement by lobster larvae in response to water jet stimuli was a hyperextension
      of the abdomen. Larval escape responses also showed very little habituation.
      Postlarval lobsters and ADI crayfish showed the same range of responses as adult
      animals. Displacement efficiency of tailflicks exhibited by the different animals
      and stages was examined and related to the morphology of the animals. A separate
      behavior from tailflicking by larval lobsters in response to water jet stimuli
      was also observed. Here, the abdomen was hyperextended and the thoracic
      appendages were promoted. We termed this behavior a "starburst" response. The
      features of the tailflicking behavior suggest that it evolved to make the larvae
      difficult prey to handle for small, slower moving predators, and possibly to
      allow them to ride the bow waves of faster moving predators.

PMID- 10897446
TI  - Catecholamines modulate metamorphosis in the opisthobranch gastropod Phestilla
      sibogae.
AB  - Larvae of the nudibranch Phestilla sibogae are induced to metamorphose by a
      factor from their adult prey, the coral Porites compressa. Levels of endogenous
      catecholamines increase 6 to 9 days after fertilization, when larvae become
      competent for metamorphosis. Six- to nine-day larvae, treated with the
      catecholamine precursor L-DOPA (0.01 mM for 0.5 h), were assayed for
      metamorphosis in response to coral inducer and for catecholamine content by high
      performance liquid chromatography. L-DOPA treatment caused 20- to 50-fold
      increases in dopamine, with proportionally greater increases in younger larvae,
      so that L-DOPA-treated larvae of all ages contained similar levels of dopamine. A
      much smaller (about twofold) increase in norepinephrine occurred in all larvae.
      The treatment significantly potentiated the frequency of metamorphosis of 7- to 9
      d larvae at low concentrations of inducer. In addition, L-DOPA treatment at 9 d
      increased aldehyde-induced fluorescence in cells that were also labeled in the
      controls, and revealed additional cells. However, all labeled cells were
      consistent with the locations of cells showing tyrosine-hydroxylase-like
      immunoreactivity. Catecholamines are likely to modulate metamorphosis in P.
      sibogae, but rising levels of catecholamines around the time of competence are
      insufficient alone to account for sensitivity to inducer in competent larvae.

PMID- 10897447
TI  - Induction of metamorphosis in the sea urchin Holopneustes purpurascens by a
      metabolite complex from the algal host Delisea pulchra.
AB  - Most benthic invertebrates have complex life cycles with planktonic larvae that
      return to the substratum to settle and metamorphose into a benthic stage.
      Although naturally produced chemical cues have long been thought to be important
      for the settlement or metamorphosis of invertebrate larvae, few ecologically
      relevant chemical cues have been clearly identified. The marine echinoid
      Holopneustes purpurascens has a complex life cycle, with a planktonic, nonfeeding
      dispersive larva that metamorphoses into a benthic stage that lives in the canopy
      of subtidal benthic algae such as the red alga Delisea pulchra and the kelp
      Ecklonia radiata. Recently recruited juveniles are found primarily on D. pulchra,
      and we hypothesized that this was in response to a chemical cue produced by this
      alga. Competent larvae metamorphosed in the presence of D. pulchra, or seawater
      surrounding this alga, but not in response to the presence of E. radiata or its
      extracts. A cue for metamorphosis was isolated and characterized from D. pulchra
      and found to be a water-soluble complex of the sugar floridoside and isethionic
      acid in a 1:1 molar ratio. The floridoside-isethionic acid complex also triggered
      settlement in H. purpurascens; however, this response was less specific than
      metamorphosis and was reversible. Larvae of H. purpurascens also metamorphosed in
      the presence of several other species of red, but not brown or green, algae from
      their habitat. Floridoside is found only in red algae, suggesting that the
      floridoside-isethionic acid complex may be acting as a cue for metamorphosis in
      other red algae as well as in D. pulchra.

PMID- 10897448
TI  - Energetics of larval swimming and metamorphosis in four species of Bugula
      (Bryozoa).
AB  - The amount of energy available to larvae during swimming, location of a suitable
      recruitment site, and metamorphosis influences the length of time they can spend
      in the plankton. Energetic parameters such as swimming speed, oxygen consumption
      during swimming and metamorphosis, and elemental carbon and nitrogen content were
      measured for larvae of four species of bryozoans, Bugula neritina, B. simplex, B.
      stolonifera, and B. turrita. The larvae of these species are aplanktotrophic with
      a short free-swimming phase ranging from less than one hour to a maximum of about
      36 hours. There is about a fivefold difference in larval volume among the four
      species, which scales linearly with elemental carbon content and, presumably,
      with the amount of endogenous reserves available for swimming and metamorphosis.
      Mean larval swimming speeds (in centimeters per second) were similar among
      species. Specific metabolic rate and larval size were inversely related. For
      larvae of a given species, respiration rates remained similar for swimming and
      metamorphosis; however, because metamorphosis lasts about twice as long as a
      maximal larval swimming phase, it was more energetically demanding. Larger larvae
      expended more energy to complete metamorphosis than did smaller larvae, but in
      terms of the percentage of larval energy reserves consumed, swimming and
      metamorphosis were more "expensive" for smaller larvae. A comparison of the
      energy expended during larval swimming calculated on the basis of oxygen
      consumption and on the basis of elemental carbon decrease suggests that larvae of
      Bugula spp. may not use significant amounts of dissolved organic material (DOM)
      to supplement their endogenous energy reserves.

PMID- 10897449
TI  - The calcium dependence of pigment translocation in freshwater shrimp red ovarian
      chromatophores.
AB  - The roles of calcium in cell signaling consequent to chromatophorotropin action
      and as an activator of mechanochemical transport proteins responsible for pigment
      granule translocation were investigated in the red ovarian chromatosomes of the
      freshwater shrimp Macrobrachium olfersii. Chromatosomes were perfused with known
      concentrations of free Ca++ (10(-3) to 10(-9) M) prepared in Mg(++)-EGTA-buffered
      physiological saline after selectively permeabilizing with 25 microM calcium
      ionophore A23187 or with 10(-8) M red pigment concentrating hormone (RPCH). The
      degree of pigment aggregation and the translocation velocity of the leading edges
      of the pigment mass were recorded in individual chromatosomes during aggregation
      induced by RPCH or A23187 and dispersion induced by low Ca++. Aggregation is Ca++
      dependent, showing a dual extracellular and intracellular requirement. After
      perfusion with reduced Ca++ (10(-4) to 10(-9) M), RPCH triggers partial
      aggregation (approximately 65%), although the maximum translocation velocities
      (approximately 16.5 microns/min) and velocity profiles are unaffected. After
      aggregation induced at or below 10(-5) M Ca++, spontaneous pigment dispersion
      ensues, suggesting a Ca++ requirement for RPCH coupling to its receptor, or a
      concentration-dependent, Ca(++)-induced Ca(++)-release mechanism. The Ca(++)
      channel blockers Mn++ (5 mM) and verapamil (50 microM) have no effect on RPCH
      triggered aggregation. An intracellular Ca++ requirement for aggregation was
      demonstrated in chromatosomes in which the Ca++ gradient across the cell membrane
      was dissipated with A23187. At free [Ca++] above 10(-3) M, aggregation is
      complete; at 10(-4) M, aggregation is partial, followed by spontaneous
      dispersion; below 10(-5) M Ca++, pigments do not aggregate but disperse slightly.
      Aggregation velocities diminish from 11.6 +/- 1.2 microns/min at 5.5 mM Ca++ to
      7.4 +/- 1.3 microns/min at 10(-4) M Ca++. Half-maximum aggregation occurs at 3.2
      x 10(-5) M Ca++ and half-maximum translocation velocity at 4.8 x 10(-5) M Ca++.
      Pigment redispersion after 5.5 mM Ca(++)-A23187-induced aggregation is initiated
      by reducing extracellular Ca++: slight dispersion begins at 10(-7) M, complete
      dispersion being attained at 10(-9) M Ca++. Dispersion velocities increase from
      0.6 +/- 0.2 to 3.1 +/- 0.5 microns/min. Half-maximum dispersion occurs at 7.6 x
      10(-9) M Ca++ and half-maximum translocation velocity at 2.9 x 10(-9) M Ca++.
      These data reveal an extracellular and an intracellular Ca++ requirement for RPCH
      action, and demonstrate that the centripetal or centrifugal direction of pigment
      movement, the translocation velocity, and the degree of pigment aggregation or
      dispersion attained are calcium-dependent properties of the granule translocation
      apparatus.

PMID- 10897450
TI  - A morphological study of nonrandom senescence in a colonial urochordate.
AB  - Botryllus schlosseri is a clonally modular ascidian, in which individuals
      (zooids) have a finite life span that is intimately associated with a weekly
      budding process called blastogenesis. Every blastogenic cycle concludes with a
      synchronized phase of regression called takeover, during which all zooids in a
      colony die, primarily by apoptosis, and are replaced by a new generation of
      asexually derived zooids. We have previously documented that, in addition to this
      cyclical death phase, entire colonies undergo senescence during which all
      asexually derived individuals in a colony, buds and zooids, die in concert. In
      addition, when a specific parent colony (genet) is experimentally separated into
      a number of clonal replicates (ramets), ramets frequently undergo senescence
      simultaneously, indicating that mortality can manifest itself in nonrandom
      fashion. Here, we document a morphological portrait of senescence in laboratory
      maintained colonies from Monterey Bay, California, that exhibit nonrandom
      mortality. Nonrandom senescence proceeded according to a series of characteristic
      changes within the colony over a period of about one week. These changes included
      systemic constriction and congestion of the vasculature accompanied by massive
      accumulation of pigment cells in the zooid body wall (mantle), blood vessels, and
      ampullae; gradual shrinkage of individual zooids; loss of colonial architecture,
      and ultimately death. At the ultrastructural level, individual cells exhibited
      changes typical of ischemic cell death, culminating in necrotic cell lysis rather
      than apoptosis. Collectively, these observations indicate that senescence is
      accompanied by unique morphological changes that occur systemically, and which
      are distinct from those occurring during takeover. We discuss our findings in
      relation to current experimental models of aging and the possible role of a
      humoral factor in bringing about the onset of senescence.

PMID- 10897451
TI  - Vestigial ophiopluteal structures in the lecithotrophic larvae of Ophionereis
      schayeri (Ophiuroidea).
AB  - Evolution of echinoderm development from a feeding to a non-feeding mode can be
      examined by studying non-feeding larvae with structures that appear to be
      vestiges derived from a feeding ancestral state. The lecithotrophic larvae of the
      Australian brittle star Ophionereis schayeri possess such features, and the early
      development of this species was documented by light and scanning electron
      microscopy. The embryos undergo irregular cleavage, resulting in the formation of
      different sized blastomeres, with subsequent development through a wrinkled
      blastula stage. The lecithotrophic larva of O. schayeri possesses several
      vestigial ophiopluteal structures, including a continuous ciliated band, a larval
      gut, and a larval skeleton. The ciliated band is a reduced expression of the
      continuous ciliated band typical of ophioplutei. The larval gut is a transiently
      complete system, but an esophageal plug and rapid closure of the blastopore
      renders it nonfunctional. The larval skeleton, though reduced, consists of four
      rods corresponding to the body, posterolateral, anterolateral, and postoral rods
      characteristic of an ophiopluteus. Due to a heterochrony in larval
      skeletogenesis, the postoral rods develop early and simultaneously with the other
      rods. Compared with the larvae of other lecithotrophic ophiuroids, the larva of
      O. schayeri is one of the most reduced ophiopluteal forms reported to date.

PMID- 10897452
TI  - Larval development of the tropical deep-sea echinoid Aspidodiadema jacobyi:
      phylogenetic implications.
AB  - The complete larval development of an echinoid in the family Aspidodiadematidae
      is described for the first time from in vitro cultures of Aspidodiadema jacobyi,
      a bathyal species from the Bahamian Slope. Over a period of 5 months, embryos
      grew from small (98-micron) eggs to very large (3071-micron) and complex
      planktotrophic echinopluteus larvae. The fully developed larva has five pairs of
      red-pigmented arms (preoral, anterolateral, postoral, posterodorsal, and
      posterolateral); fenestrated triangular plates at the bases of fenestrated
      postoral and posterodorsal arms; a complex dorsal arch; posterodorsal vibratile
      lobes; a ring of cilia around the region of the preoral and anterolateral arms;
      and a long, unpaired posterior process containing a fenestrated rod. The presence
      of a posterior process and posterodorsal arms makes the larva of Aspidodiadema
      jacobyi much more similar to larvae of irregular urchins in the order
      Spatangoidea than to other families of the order Diadematoida, to which the
      family is normally assigned. This unexpected larval form lends support to a
      recommendation that the Aspidodiadematidae should be either elevated to ordinal
      status as a sister group of the order Diadematoida, or split off as a sister
      group of the other families within the order. In either case, if we accept the
      parsimonious hypothesis that the aboral process and posterodorsal arms were
      derived only once in the evolutionary history of euechinoids, then the larval
      data suggest that the Aspidodiadematidae may be very near the node where the
      irregular and regular euechinoids first diverged.

PMID- 10897453
TI  - Genetic diversity of oceanic island Lasaea (Mollusca: Bivalvia) lineages exceeds
      that of continental populations in the northwestern Atlantic.
AB  - Direct-developing lineages of the intertidal marine bivalve Lasaea have colonized
      both upstream mainland (southeastern Florida) and downstream oceanic island
      (Bermuda) locations in the western North Atlantic. Replicate samples from these
      two regional populations, separated by about 1500 km of open ocean, were
      sequenced for a 655-nucleotide portion of the mitochondrial (mt) cytochrome
      oxidase subunit I gene. Twelve haplotypes (2 Floridian and 10 Bermudan) were
      obtained that differed by a maximum of four substitutions among pairwise
      comparisons. Phylogenetic analysis yielded a parsimony network within which the
      mainland lineages clustered in one of the terminal branches; a mirror image of a
      priori expectations based on regional surface-current polarity. It is difficult,
      however, to envisage a plausible countercurrent dispersal mechanism. This tree
      topology may stem from divergent demographic processes operating on these two
      evolutionarily recent regional populations. The starlike phylogenetic pattern of
      Bermudan lineages is consistent with a history of rapid population growth. The
      restricted genetic repertoire and relative ecological scarcity of Floridian
      lineages imply either a recent founder event by unstudied Caribbean source
      populations or else a history of pronounced bottlenecks in population size.
      Bermuda's impoverished Caribbean marine biota may allow western North Atlantic
      Lasaea lineages to escape severe competitive interactions impacting other parts
      of their geographic range.

PMID- 10897454
TI  - Cuttlebone morphology limits habitat depth in eleven species of Sepia
      (Cephalopoda: Sepiidae).
AB  - The cuttlebone is a rigid buoyancy tank that imposes a depth limit on Sepia, the
      only living speciose cephalopod genus with a chambered shell. Sections of 59
      cuttlebones from a geographically diverse sample of 11 species were examined
      using confocal microscopy. Sepia species that live at greater depths had thicker
      septa and less space between pillars than did shallow species. A plate theory
      analysis of cuttlebone strength based on these two measures predicted maximum
      capture depths accurately in most species. Thus cuttlebone morphology confers
      differing degrees of strength against implosion from hydrostatic pressure, which
      increases with increasing habitat depth. Greater strength may come at the cost of
      increased cuttlebone density, which impinges on the cuttlebone's buoyancy
      function.

PMID- 10897455
TI  - Using the Baldrige management system framework in health care: the Veterans
      Health Administration experience.
AB  - BACKGROUND: In 1998 the Veterans Health Administration (VHA) developed the
      Quality Achievement Recognition Grant, a competitive grant application open to
      all Veterans Integrated Service Networks (VISNs) within the VHA system and based
      on the Baldrige management framework. Eight of the 22 VISNs attended the
      educational programs and initiated the grant application process; 7 completed
      applications. Team award experts from VHA and external sources reviewed, scored,
      and wrote feedback reports to all applicants and conducted four site visits.
      IDENTIFICATION OF BEST PRACTICES AND RECOMMENDATIONS FOR FUTURE APPLICANTS: Each
      application was compared to examples of ideal applications to identify areas of
      excellence and areas for improvement. In general, the best applicants identified
      and described key processes and articulated the methods used to evaluate and
      improve processes. For example, they were able to identify the process used to
      incorporate key constituents into the strategy development process. One applicant
      developed a series of management advisory committees, the membership of which
      includes veterans' service organizations, academic affiliates, community members,
      and congressional delegates, which were tapped to develop a strategic plan.
      Leading applicants in the future are likely to be able to demonstrate evidence of
      deployment and constant review of the strategy and to emphasize the human
      resources plan into the strategic planning and deployment. CONCLUSIONS: The
      Baldrige management framework is a useful tool for identification of areas of
      achievement and areas for improvement within the VHA. Potential applicants for
      the award could benefit from ensuring coherence across the application, placing a
      greater emphasis on work systems, and incorporating more extensive analysis of
      market conditions.

PMID- 10897456
TI  - Effecting and leading change in health care organizations.
AB  - BACKGROUND: Understanding change is crucial to implementing quality improvement
      (QI) initiatives. Widespread change will be required to correct what many
      consider to be outmoded and deficient systems of care. This article summarizes
      the current literature--within both health care and the fields of business and
      management--regarding how change occurs at the individual and organizational
      levels. Part 1 focuses on changing clinician behavior, which is instrumental to
      any effort directed in the health care setting. Part 2 examines the culture of
      change. Part 3 addresses issues of leadership, along with the necessary steps to
      guide change in an organization. Part 4 summarizes key elements of change.
      Finally, Part 5 provides three case examples of QI initiatives reported in the
      recent literature to illustrate how the application of the knowledge of change
      management can assist in the successful implementation of QI programs. KEY
      ELEMENTS OF CHANGE: The knowledge base regarding successful change in health care
      organizations can be summarized in eight crucial strategies or principles: (1)
      develop a vision for change, (2) focus on the change process, (3) analyze which
      individuals in the organization must respond to the proposed change and what
      barriers exist, (4) build partnerships between physicians and the administration,
      (5) create a culture of continuous commitment to change, (6) ensure that change
      begins with leadership, (7) ensure that change is well communicated, and (8)
      build in accountability for change. CONCLUSION: A knowledge of change management
      can help leaders of QI programs in health care organizations successfully apply
      these concepts to bring about much-needed transformations in health care.

PMID- 10897457
TI  - Does patient-centered care pay off?
AB  - BACKGROUND: Hospitals have adopted patient-centered practices that focus on
      patients' needs, values, and preferences in hopes of improving quality and
      controlling costs. Patient-centered practices are intended to involve patients in
      treatment decisions, increase communication between patients and care-givers, and
      increase interaction with family members and friends. Rapid adoption of these
      practices has occurred, even though little is known about the effects of patient
      centered care on outcomes and cost. METHODS: A simultaneous equations regression
      model was developed to examine the reciprocal relationships between patient
      centeredness, outcomes, and cost. A consortium of employers obtained data from 52
      hospital units in southeastern Michigan. Two hundred randomly selected patients
      were sampled from all discharges on the medical, surgical, and obstetric units at
      each hospital for the first three months of 1997; the patients were sent the
      survey in May. Patient-centeredness was measured by patient reports of whether
      key clinical events occurred (The Picker Inpatient Survey). Outcomes were
      assessed by rates of unexpected mortality and complications. Cost was defined by
      self-insured purchaser payments. RESULTS: Hospital units that were more patient
      centered were associated with statistically significantly better outcomes and
      higher costs than those that were less patient centered. The joint relations
      between outcomes and cost were insignificant. CONCLUSIONS: Patient-centeredness
      was associated with better outcomes and higher cost. For either the short run or
      long run, managers, patients, and purchasers should determine whether the
      improvement in outcomes and patient satisfaction associated with becoming patient
      centered is worth the investment in costs.

PMID- 10897458
TI  - Providing consumers with information about the quality of health plans: the
      Consumer Assessment of Health Plans demonstration in Washington State.
AB  - BACKGROUND: In 1995 the Agency for Health Care Policy and Research began a five
      year project, Consumer Assessment of Health Plans (CAHPS), to create instruments
      to collect data from consumers about their health care experiences, to develop
      sophisticated methods to convey these data to consumers, and to evaluate the
      value of these data to consumers who are selecting health plans. Results were
      obtained from one of the first CAHPS demonstration sites, the Washington State
      Health Care Authority. METHODS: The survey was distributed in May-June 1997 to
      15,885 enrollees in 20 health plans; 8,204 (51.6%) surveys were completed. Survey
      results were summarized in a report that described the performance of plans,
      which was distributed to 97,000 enrollees, and reactions to the report were
      obtained from more than 1,500 individuals. RESULTS: Nearly everyone who was
      mailed the report said they saw it. A large proportion said they read most or all
      of it, and most thought the report was easy to understand, contained information
      needed to rate plans, and was helpful to learning about differences between
      plans. Those who used the CAHPS performance report were more likely to switch
      plans and to report that they were confident they had selected the best plan for
      their situation. DISCUSSION: The study was unique in that it attempted to
      evaluate whether employees read the performance report, how they reacted to it,
      and whether reading it influenced their decision to switch plans or their
      confidence that they had selected a suitable plan. Choosing a new plan probably
      stimulated more intense scrutiny of the report than not anticipating switching.

PMID- 10897459
TI  - Implementing emergency department observation units within a multihospital
      network.
AB  - BACKGROUND: The proportion of emergency department (ED) chest pain patients who
      undergo an extended "rule out MI (myocardial infarction)" evaluation beyond the
      ED determines both the quality and cost of patient care. The higher an
      organization's rate of such evaluations, the lower the average miss rate for MI.
      Five of the 13 hospitals in the Voluntary Hospital Association Northeast
      multihospital network implemented ED observation units by June 1997 for
      outpatient rule out MI evaluations. RESULTS: Compared with historical and case
      controls, the five hospitals with ED observation units had a higher observation
      rate (16% versus 0% [p < .001] and 2% [p < .001]) and a higher rule out MI
      evaluation rate (61% versus 46% [p < .01] and 45% [p < .01]), without a
      significantly higher admission rate (47% versus 46% and 45%). For the three
      hospitals with observation units that collected charge data during 1997 on a
      consecutive series of chest pain patients who had negative rule out MI
      evaluations, charges for patient services were lower for patients evaluated in
      the ED observation unit ($2,214.80 +/- $80.40) than in the hospital ($5,464.30 +/
      $393.60). CONCLUSIONS: ED observation units represent a cost-effective
      restructuring of the diagnostic approach to patients with acute chest pain. In an
      improvement of quality of patient care, a larger proportion of ED chest pain
      patients receive an extended evaluation than is possible with hospital admission
      as the only ED disposition option.

PMID- 10897460
TI  - The AMA clinical quality improvement forum on addressing patient safety.
AB  - BACKGROUND: More than 200 health care policy makers and researchers, clinicians,
      quality professionals, and other representatives of health care organizations,
      government, and academia attended the Division of American Medical Association
      Clinical Quality Improvement's conference, "Addressing Patient Safety," April 28,
      2000, in Chicago--the first national conference to respond to the recent
      Institute of Medicine (IOM) report, To Err Is Human: Building a Safer Health
      System. ADDRESSING PATIENT SAFETY--PUBLIC AND PRIVATE PERSPECTIVES: John M.
      Eisenberg, MD, stated that research on errors is needed to describe the scope and
      nature of the problem, understand the barriers to and benefits of improvement,
      and develop and test strategies for improvement. Kenneth W. Kizer, MD, MPH,
      stated that the National Quality Forum will develop a compendium of best
      practices and will develop core measures for serious adverse events, and health
      care organizations and government health programs should act now to make a clear
      organizational commitment to patient safety, create a nonpunitive health care
      culture of safety, and implement known safe medication practices. Alan R. Nelson,
      MD, stated that the IOM report places its emphasis on continuous quality
      improvement and technology that can be used to mitigate the risks in a complex
      health system. HOSPITAL AND ACCREDITATION AGENCY ACTIVITIES ON PATIENT SAFETY
      ISSUES: Donald M. Nielsen, MD, discussed the American Hospital Association's
      (AHA's) Medication Safety Initiative, which promised to provide its members with
      successful practices, tools, and resources and to track progress of
      implementation of the recommended successful practices. Dennis S. O'Leary, MD,
      stated that when a hospital reports a sentinel event, the hospital is expected to
      implement improvements to reduce risk and monitor their effectiveness. The
      National Committee for Quality Assurance is considering changes to its
      accreditation standards to further address patient safety.

PMID- 10897461
TI  - A practical way to diagnosis personality disorder: a proposal.
AB  - General criteria for the diagnosis of personality disorder are provided based on
      rating a few items describing four core features of personality disorder: (a) low
      Self-directedness, (b) low Cooperativeness, (c) low Affective Stability, and (d)
      low Self-transcendence. These core features correspond closely with the basic
      concept of personality disorder in DSM-IV and are based on specific items easy
      for clinicians to rate in a short time. Criteria are also provided for rating
      severity of personality disorganization and for subtyping based on a profile of
      three additional dimensions corresponding to core features of DSM-IV clusters A,
      B, and C. This approach should facilitate efficient screening in clinical
      practice, encourage an understanding of the development of comorbidity as a self
      organizing process, and provide a theory-driven basis for therapeutic planning
      with drugs and psychotherapy.

PMID- 10897462
TI  - A prototype matching approach to diagnosing personality disorders: toward DSM-V.
AB  - The current diagnostic system for personality disorders (PD) has a number of
      problems that may require a thorough revision for DSM-V. This article (a)
      outlines problems with the current taxonomy that suggest the need for a different
      approach to PD diagnosis that preserves the strengths of the current system while
      addressing some inherent weaknesses; (b) discusses key issues that must be
      addressed in moving toward DSM-V, such as revising the distinction between Axis I
      and Axis II and combining categorical and dimensional diagnosis; and (c)
      describes a prototype matching approach to diagnosis, which we believe has the
      potential to be both psychometrically sound and faithful to the clinical data.

PMID- 10897463
TI  - The classification of personality disorders should be rooted in biology.
AB  - As scientific classifications develop over time, they become based less on
      observations and more on mechanisms. Existing dimensional schema are limited by
      being overly broad and by being rooted in self-report rather than theory. Future
      models should be consistent with a scientific hierarchy, leading to a bottom-up
      classification of traits and disorders, linking molecular genetics,
      neurobiological markers, and temperamental variations.

PMID- 10897464
TI  - Toward an empirically based classification of personality disorder.
AB  - A framework for an empirically based classification of personality disorder is
      proposed that has two components: (a) a definition of personality disorder, and
      (b) a scheme for describing individual differences in personality disorder
      traits. It is suggested that the diagnosis process should begin by establishing
      the presence of personality disorder and then proceed to a description of the
      personality on a set of trait dimensions. It is argued that a definition of
      personality disorder should reflect an understanding of the nature of the
      "harmful dysfunction" implied by a diagnosis of personality disorder. With this
      approach, personality disorder is defined as the failure to solve life tasks
      involving the development of integrated representations of self and others, and
      the capacity for adaptive kinship and societal relationships. The second
      component of a classification is a system to describe individual differences. It
      is suggested that these should be based on taxonomies of normal and disordered
      traits, and that the classification incorporates both higher-order patterns and
      more specific basic traits. Given that personality appears to be inherited as a
      large number of genetic dimensions, it is suggested that the primary level for
      describing individual differences is that of the basic or lower-level traits
      rather than broader or higher-level traits used in descriptions of normal
      personality.

PMID- 10897465
TI  - Personality assessment of homeless adults as a tool for service planning.
AB  - The psychiatric status of homeless adults has been described primarily in terms
      of Axis I disorders. By adding a subset of the Personality Assessment Inventory,
      this study tests the feasibility and usefulness of a brief, self-administered
      questionnaire to obtain scores on several dimensions of personality. Cluster
      analysis sorted 112 tested subjects into four groups characterized by distinct
      profiles. Two of these were characterized by extreme scores on pathological
      dimensions of personality (borderline features, antisocial traits, and
      aggressivity) and differed primarily on the dimension of suicidality. The third
      reflected moderate levels of personality dysfunction and the fourth did not
      deviate from adult nonclinical norms. The validity of the clusters was supported
      by demographic, background, and diagnostic subgroup differences. Brief
      personality assessment can be a cost-effective approach to matching services with
      clinical needs of homeless adults by attending to interpersonal dimensions that
      will likely affect service provision.

PMID- 10897466
TI  - Personality disorders in a Dutch forensic psychiatric sample: convergence of
      interview and self-report measures.
AB  - Convergence of PDQ-R- and SIDP-R-derived personality disorder diagnoses was
      studied in a sample of 85 forensic psychiatric patients. For categorical
      diagnoses, the mean kappa was .34, but on a dimensional level convergence was
      somewhat higher. Paranoid, antisocial and borderline personality disorders had
      prevalence rates around 40%; the other personality disorders occurred with much
      lower frequency. The PDQ-R yielded more diagnoses, except for antisocial,
      histrionic, narcissistic, and sadistic personality disorder. Because the latter
      disorders are among the most prevalent in forensic settings, and because they
      have important risk and treatment implications, the PDQ-R is not suitable as a
      screening device in forensic populations. Semistructured interviews that make use
      of collateral information are recommended for diagnosing personality disorders in
      forensic subjects.

PMID- 10897467
TI  - Associations between four types of childhood neglect and personality disorder
      symptoms during adolescence and early adulthood: findings of a community-based
      longitudinal study.
AB  - Data from a community-based longitudinal study were used to investigate the
      association between childhood neglect and personality disorder (PD) symptom
      levels during adolescence and early adulthood. Psychosocial and psychiatric
      interviews were administered to a representative sample of 738 youths and their
      mothers from upstate New York in 1975, 1983, 1985-1986, and 1991-1993. Evidence
      of childhood cognitive, emotional, physical, and supervision neglect was obtained
      from the maternal interviews that were conducted in 1975, 1983, and 1985-1986,
      and from New York State records. PDs were assessed among the youths in 1985-1986,
      when they were adolescents, and in 1991-1993, when they were young adults.
      Findings indicated that childhood emotional, physical, and supervision neglect
      were associated with increased risk for PDs and with elevated PD symptom levels
      during adolescence and early adulthood, after age, sex, childhood physical or
      sexual abuse, other types of childhood neglect, and cooccurring PD symptoms were
      controlled statistically. Childhood emotional neglect was associated with
      increased risk for avoidant PD and with paranoid and Cluster A PD symptom levels
      during adolescence and early adulthood. Childhood physical neglect was associated
      with increased risk for schizotypal PD and with Cluster A PD symptom levels
      during adolescence and early adulthood. Childhood supervision neglect was
      associated with increased risk for passive-aggressive and Cluster B PDs and with
      borderline, paranoid, and passive-aggressive PD symptom levels during adolescence
      and early adulthood. The present findings suggest that childhood emotional,
      physical, and supervision neglect may play a role in the etiology of some PDs.

PMID- 10897468
TI  - Measurement of flow characteristics during individual contractions in bovine
      mesenteric lymphatic vessels.
AB  - We developed a novel technique for measuring flow characteristics during
      individual contractions in lymph vessels. Bovine mesenteric lymph vessel segments
      (n = 15) were mounted in organ baths and allowed to equilibrate for 1 hr.
      Transmural pressure was subsequently increased by 2 cm H2O increments at 15 min
      intervals and vessel outputs were collected during the final 10 min of each
      period and measured. Flow also was continuously recorded with an in-line Doppler
      transducer connected to a flow analyzer, and flow characteristics were analyzed.
      The two methods of flow measurement correlated well (r2 = 0.92). Mean flow
      increased with increasing transmural pressure and reached a maximum of 0.5 +/-
      0.1 ml/min at a transmural pressure of 8 cm H2O. The rate of spontaneous
      contractions, the peak flow during a contraction-induced wave, and the total
      volume of flow during a wave also increased with increasing transmural pressure
      and reached maximums of 12.4 +/- 1.0 min-1, 8.2 +/- 1.6 ml/min, and 0.21 +/- 0.06
      ml, respectively. Wave duration changed little in response to changes in
      transmural pressure. Continuous in-line flow measurement is an accurate technique
      for assessing flow characteristics during individual contractions in lymph
      vessels in vitro. Transmural pressure regulates flow by influencing spontaneous
      contraction frequency and total and peak flows during contraction-induced waves.

PMID- 10897469
TI  - Lipedema complicated by lymphedema of the abdominal wall and lower limbs.
AB  - We describe a 52 year-old woman in whom lymphedema primarily of the abdominal
      wall was superimposed on lipedema resulting in an abdomen of enormous dimensions
      with marked impairment of ambulation. Treatment consisted of preoperative
      compression of the legs by an external pneumatic device (Lympha-Press) followed
      by excision of the lymphedematous abdominal fat pad in conjunction with
      "debulking" of the right leg. The patient illustrates the extremes of lipedema
      complicated by lymphedema and the technical difficulties associated with its
      management.

PMID- 10897470
TI  - The functional evolution of GALT: a review.
AB  - This synopsis of the evolution of gut-associated lymphoid tissue (GALT) in
      increasingly complex animals suggests that GALT plays an essential role in
      cellular nutrition and energy metabolism as well as in immunity. Throughout
      phylogeny, the mediation of immunity as well as cell nutrition depends on the
      normal capacity of GALT to produce lymphocytes which customarily generate an
      evolving variety of soluble globulins during maturation and proceed to migrate
      throughout the body as emperipoletic cytoplasm-depleted cells which donate their
      residual constituents to genetically compatible cells; and destroy living matter
      recognized as genetically incompatible. A dividend is that the lymphocytes not
      only destroy the genetically foreign but also render the remains innocuous or
      useful as food.

PMID- 10897471
TI  - The effects of manually applied intermittent pulsation pressure to rat ventral
      thorax on lymph transport.
AB  - The present study evaluated the effects of tissue massage on a part of the body
      remote from the region of lymph uptake into the initial lymphatics. Lymph uptake
      was assessed with a fluorescent probe placed in a potential space of the lower
      extremity of anesthetized female Sprague-Dawley rats. Tail blood was assayed at
      intervals over 15 hours for fluorescence. A total of 63 animals were utilized
      (treatment = 32 and control = 31). The manipulated group received lymph flow
      enhancing treatment (LFET) five minutes per rat per hour until they were aroused.
      The control group were left lying prone in cages until a blood sample was taken.
      The LFET procedure was bilateral finger pressure applied to the lower ribs of a
      supine rat followed immediately by a light tap to the sternum. These maneuvers
      were repeated for 5 minutes. The rate of appearance of fluorescent probe was
      greater during the first nine hours of the experiment in the treatment group than
      in the controls but not at hours 12 and 15. This study demonstrates that
      mechanical pressure to body regions physically distant from the location of lymph
      formation enhances lymph uptake.

PMID- 10897472
TI  - Prostaglandin synthesis in human lymphatics from precursor fatty acids.
AB  - (Iso)-eicosanoids appear to play a pivotal role in lymphatic contractility.
      Because prostaglandin (PG)I2, an arachidonic acid (20:4) metabolite, is a key
      substance generated by human lymphatics, both from exogenous and endogenous
      substrates, it is reasonable to assume that altered nutritional intake of
      precursor fatty acids (FA) influences formation of respective eicosanoids
      qualitatively and quantitatively, and thereby modify its biological effects on
      human lymphatics. We, therefore, examined the effect of 2 other FA-precursors,
      dihomo-gamma-linolenic (20:3) and eicosapentaenoic acid (20:5) on the formation
      of the respective PG-metabolites in human lymphatics removed from the legs in
      patients undergoing amputation after traumatic injury. 20:3 and 20:5 were poorer
      substrates to form PGs. Because these PGs exert different biological actions and
      their synthesis may be altered by vascular environmental risk factors such as
      cigarette smoking, diabetes mellitus, hyperlipidemia, and availability of FA
      precursors and therefore nutrition, PGs may profoundly modulate the lymphatic
      contractile response under a variety of circumstances. The full effect of all the
      formed compounds of the 1- and 3-series PGs on lymph vessel contractility,
      however, still needs to be tested.

PMID- 10897473
TI  - Dendritic (Langerhans) cells in central lymph of rabbits.

PMID- 10897474
TI  - Effects of compression bandaging...

PMID- 10897475
TI  - Oxidation of xenobiotics by plant microsomes, a reconstituted cytochrome P450
      system and peroxidase: a comparative study.
AB  - The microsomal fraction from tulip bulbs (Tulipa fosteriana, L.) contains
      cytochrome P450 (CYP3, EC 1.14.14.1) and peroxidase (EC 1.11.1.7.) enzymes
      catalyzing the NADPH--and hydrogen peroxide--dependent oxidation of the
      xenobiotic substrates, N-nitrosodimethylamine (NDMA), N-nitrosomethylaniline
      (NMA), aminopyrine and 1-phenylazo 2-hydroxynaphthalene (Sudan I), respectively.
      Oxidation of these model xenobiotics has also been assessed in a reconstituted
      electron-transport chain with a partially purified CYP fraction, phospholipid and
      isolated tulip NADPH:CYP reductase (EC 1.6.2.4.). Peroxidase isolated from tulip
      bulbs (isoenzyme C) oxidizes these xenobiotics, too. Values of kinetic parameters
      (Km, Vmax), requirements for cofactors (NADPH, hydrogen peroxide), the effect of
      inhibitors and identification of products formed from the xenobiotics by the
      microsomal fraction, partially purified CYP and peroxidase C were determined.
      These data were used to estimate the participation of the CYP preparation and
      peroxidase C in oxidation of two out of the four studied xenobiotics (NMA, Sudan
      I) in tulip microsomes. Using such detailed study, we found that the CYP
      dependent enzyme system is responsible for the oxidation of these xenobiotics in
      the microsomal fraction of tulip bulbs. The results demonstrate the progress in
      resolving the role of plant CYP and peroxidase enzymes in oxidation of
      xenobiotics.

PMID- 10897476
TI  - Species identification of Radix Astragali (Huangqi) by DNA sequence of its 5S
      rRNA spacer domain.
AB  - About 300 species and varieties of Astragalus are identified in China, making the
      identification of the origin of a particular Astragalus species on the consumer
      market difficult. A molecular genetic approach was developed to identify various
      species of Astragalus. Although the 5S-rRNA coding sequence is conserved in
      higher eukaryotes, the spacer domain of the 5S-rRNA gene has great diversity
      among different species. The 5S-rRNA spacer domain was amplified by polymerase
      chain reaction (PCR) from the isolated genomic DNA, and the PCR products
      (approximately 300 bp) covering the 5S-rRNA spacer domain were sequenced. The
      nucleotide sequences of Astragalus membranaceus, A. membranaceus var.
      mongholicus, A. lehmannianus, A. hoantchy, and of one closely related species
      Hedysarum polybotrys (Hongqi), were determined. Diversity in DNA sequence and
      restriction enzyme mapping among various species was found in their 5S-rRNA
      spacer domains. This is the first report on the detection of 5S-rRNA spacer
      region sequence of Astragalus, and the results could be used for genetic
      identification of Huangqi.

PMID- 10897477
TI  - Comparison of neutral lipid profile of various trilaminar outer cell wall (TLS)
      containing microalgae with emphasis on algaenan occurrence.
AB  - The neutral lipid profiles of nine species of thin trilaminar outer wall (TLS)
      containing freshwater and marine microalgae from the class of Chlorophyceae were
      studied with emphasis on the relationship between the lipid content and the
      occurrence of insoluble non-hydrolysable biopolymer (i.e. algaenan). All the
      freshwater microalgae produce a highly aliphatic algaenan. In sharp contrast, no
      algaenan was isolated from the two marine microalgae, Chlorella marina and
      Chlorella minutissima marina, supporting the absence of a close relationship
      between the presence of TLS and the occurrence of algaenan. High molecular weight
      straight-chain hydrocarbons (C23-C29) were identified in most of the algaenan
      producing microalgae and in the algaenan-devoid C. minutissima marina, whereas
      only low molecular weight hydrocarbons were detected in algaenan-producing
      Scenedesmus subspicatus and in algaenan-devoid C. marina. Sterols, phytol and
      fatty alcohols were the major constituents of the polar fraction of the neutral
      lipids of all the microalgae investigated. High molecular weight saturated or
      mono-unsaturated alcohols were detected in C. emersonii and in all the microalgae
      belonging to the genus Scenedesmus. High amounts of saturated C30 and C32
      alpha,omega-diols were also detected in S. subspicatus, S. armatus and S.
      pannonicus. Three classes of lipids were encountered in very small amounts in the
      medium polarity fraction of the neutral lipids of the microalgae investigated:
      (i) Monoesters composed predominantly of saturated C16 or C18 fatty acids and
      saturated C8, C16 or C18 alcohols and (ii) long-chain methyl ketones from C25 to
      C31 were detected in several species and (iii) methyl esters of fatty acids
      ranging from C16 to C28 were identified in all the microalgae. Attempts to use
      the neutral lipid composition and particularly the unusual long-chain lipids, as
      specific indicators of the occurrence of algaenan in TLS-containing microalgae
      were unsuccessful.

PMID- 10897478
TI  - Stereochemical fate of C-26 and C-27 during the conversion of isofucosterol to
      sitosterol and of 24-methylenecholesterol to campesterol and
      dihydrobrassicasterol in Oryza sativa cell cultures.
AB  - Administration of pro-R-methyl-13C-labeled isofucosterol to cultured cells of
      Oryza sativa revealed that the pro-R and pro-S methyls at C-25 become the pro-R
      and pro-S methyls at C-25 of sitosterol, respectively. Similar administration
      experiments using pro-S-methyl-13C-labeled 24-methylenecholesterol established
      that the pro-R and pro-S methyls at C-25 of 24-methylenecholesterol become the
      pro-R and pro-S methyls of campesterol, and the pro-S and pro-R methyls of
      dihydrobrassicasterol, respectively. These results are compatible with our
      recently proposed 'syn-SE2' mechanism' for double bond isomerization of delta
      24(28) into delta 24(25).

PMID- 10897479
TI  - Induction of clovamide by jasmonic acid in red clover.
AB  - The effect of jasmonic acid (JA) on the secondary metabolism of 5-day-old red
      clover seedlings was investigated. Induction of the formation of four compounds
      was found in roots after treatment with 50 microM JA for 48 h, while no induction
      was observed in the shoots. These compounds, whose formation was induced by JA
      addition, were isolated and identified as caffeoyl DOPA (clovamide),
      caffeoyltyrosine, p-coumaroyl DOPA and p-coumaroyltyrosine, by ion-spray MS and
      1H NMR analyses, and by chemical synthesis. Among them, clovamide was the most
      abundant, while the other amides represented only a minor portion. Clovamide
      started to increase in amount 24-36 h after treatment and reached a maximum after
      96 h (2.81 nmol/mg fr. wt.). The induction of their formation was observed even
      with 5 microM of JA, and the amount increased with concentrations up to 100
      microM. Treatment with 1 mM CuCl2, which elicits accumulation of the phytoalexin
      maackiain in red clover, caused a decrease in clovamide amount.

PMID- 10897480
TI  - The effect of growth temperature on the long-chain alkenes composition in the
      marine coccolithophorid Emiliania huxleyi.
AB  - The hydrocarbon fraction of a pure culture of Emiliania huxleyi, composed of a
      mixture of C31, C33, C37 and C38 polyunsaturated n-alkenes, appeared strongly
      dependent on the growth temperature of the alga between 8 degrees C and 25
      degrees C. The total hydrocarbon content increased linearly with decreasing
      temperatures. C37 and C38 alkenes (which accounted for more than 90% of the total
      hydrocarbons) showed distinct changes in distribution compared to C31 and C33
      alkenes, suggesting different biological syntheses and/or functions for these two
      groups of compounds. C37 and C38 alkenes and C37 methyl ketones (alkenones) all
      showed a trend to lower proportions of the two diunsaturated isomers and to
      higher proportions of the corresponding trienes with decreasing temperature.
      Unlike the alkenone unsaturation ratio (U37k'), ratios based on the C37 and C38
      alkadi- and trienes could be linearly related to the growth temperature of E.
      huxleyi only between 15 degrees C and 25 degrees C. The modifications in the
      distribution of alkenes induced by varying temperature appeared, however, to be
      twice as fast as the modifications undergone by the alkenones. Although
      structurally and biochemically related, the distinct evolutions of alkenes and
      alkenones in response to changes in growth temperature might indicate that these
      two classes of compounds play two distinct physiological functions. The non
      systematic linearity of relationships to temperature of parameters based on
      alkenes distribution suggested that these compounds are of limited use as
      paleotemperature indicator in the marine environment in contrast with the
      alkenones.

PMID- 10897481
TI  - Occurrence of diacylglyceryltrimethylhomoserines and major phospholipids in some
      plants.
AB  - Over 40 higher plant species were examined for the contents of total lipids,
      phospholipids, diacylglyceryl-N,N,N-trimethylhomoserine (DGTS),
      phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol
      (PG) by using micro-HPTLC. The results showed a wider range of plants containing
      betaine lipids. So, DGTS was found in some higher plant species, not studied
      earlier, belonging to Equisetophyta, Polypodiophyta; the lipid composition of
      many other species from Spermatophyta was also studied. It was demonstrated that
      more primitive plant species contained, as a rule, the betaine lipid DGTS. The
      quantitative data for the distribution of the main phospholipid classes PC, PE,
      and PG in various plant species and their tissues are given in this paper.

PMID- 10897482
TI  - Anti-inflammatory and immunologically active polysaccharides of Periandra
      mediterranea.
AB  - Three polysaccharides, glucans with mean M(r)'s of 1.5 x 10(5), 3.6 x 10(4) and
      2.1 x 10(4), were isolated from dried roots of Periandra mediterranea by
      fractionation on Sephacryl S-300 HR and Sephadex G-25. Chemical and spectroscopic
      studies indicated that they have a highly branched glucan type structure composed
      of alpha-(1-->4) linked D-glucopyranose residues with both (3-->4) and (4-->6)
      branching points. The polysaccharides enhance phagocytosis in vivo, and exhibit
      anti-inflammatory activity.

PMID- 10897483
TI  - An antimalarial stilbene from Artocarpus integer.
AB  - Antimalarial activity-guided study of the aerial parts of Artocarpus integer led
      to the isolation of the prenylated stilbene, trans-4-(3-methyl-E-but-1-enyl)
      3,5,2',4'-tetrahydroxystilbene with an EC50 of 1.7 micrograms/ml against
      Plasmodium falciparum in culture. The known stilbenes, trans-4-isopentenyl
      3,5,2',4'-tetrahydroxystilbene and 4-methoxy-2,2-dimethyl-6-(2-(2,4
      dihydroxy)phenyl-trans-ethenyl)chromene , were also isolated. Structures of these
      compounds were deduced on the basis of their spectral data.

PMID- 10897484
TI  - Betalains from Christmas cactus.
AB  - The presence of 14 betalain pigments have been detected by their characteristic
      spectral properties in flower petals of Christmas cactus (Schlumbergera x
      buckleyi). Along with the known vulgaxanthin I, betalamic acid, betanin and
      phyllocactin (6'-O-malonylbetanin), the structure of a new phyllocactin-derived
      betacyanin was elucidated by various spectroscopic techniques and carbohydrate
      analyses as betanidin 5-O-(2'-O-beta-D-apiofuranosyl-6'-O-malonyl)-beta-D
      glucopyranosid e. Among the more complex betacyanins occurring in trace amounts,
      the presence of a new diacylated betacyanin ?betanidin 5-O-[(5"-O-E-feruloyl)-2'
      O-beta-D- apiofuranosyl-6'-O-malonyl)]-beta-D-glucopyranoside? has been
      ascertained. Furthermore, the accumulation of betalains during flower development
      and their pattern in different organs of the flower has been examined.

PMID- 10897485
TI  - Six novel tetraterpenoid ethers, lycopanerols B-G, and some other constituents
      from the green microalga Botryococcus braunii.
AB  - Six novel tetraterpenoid ethers, lycopanerols B-G, were isolated from lipidic
      extracts of the green microalga Botryococcus braunii (L race), along with a
      series of phytyl esters and alpha- and beta-tocopherols. The structures of the
      compounds were determined by means of spectral analyses including 2D NMR
      techniques. A biogenetic relationship is proposed between lycopanerols and
      lycopadiene, the acyclic diunsaturated tetraterpenoid hydrocarbon synthesized by
      the alga.

PMID- 10897486
TI  - Lignans causing photodiscoloration of Tsuga heterophylla: 8-hydroxy
      oxomatairesinol from sapwood.
AB  - A lignan, (8S,8'S,)-(+)-8-hydroxy-oxomatairesinol, has been isolated from the
      sapwood of Tsuga heterophylla (western hemlock, Pinaceae). The known lignans
      matairesinol, lariciresinol and secoisolariciresinol were also obtained. The
      structure of the compound was established by 1D and 2D NMR spectroscopy. Results
      of the light-irradiation test of the lignans from T. heterophylla are also
      reported.

PMID- 10897487
TI  - Effects of concentrated ambient particles in rats and hamsters: an exploratory
      study.
AB  - Considerable controversy surrounds the biological plausibility of adverse effects
      from exposure to ambient particulate matter (PM)*, chiefly because these adverse
      effects have been observed at particle mass concentrations below those that have
      been shown to produce effects in healthy animals and human volunteers in the
      laboratory. To address this research gap, we examined the potential for
      concentrated ambient PM to produce pulmonary and cardiovascular changes in
      compromise rodent models. Normal healthy and monocrotaline-treated rats received
      single or multiple exposures to concentrated ambient PM, and their responses were
      tested using functional, cellular, biochemical, and histological endpoints.
      Analyses determined that no changes in pulmonary function or structure occurred
      after exposure to concentrated ambient PM. Cardiac arrhythmias did not increase
      after PM exposure in normal or monocrotaline-treated rats. Increased atrial
      conduction time, accompanied by a decrease in the duration of the T wave portion
      of the electrocardiogram (ECG) waveform, was observed in PM-exposed monocrotaline
      treated rats in one experiment. In addition, on several but not all exposure
      days, small yet statistically significant increases in heart rate and peripheral
      blood cell differential counts were observed in normal and monocrotaline-treated
      rats within 6 hours after exposure to concentrated ambient PM. The observed
      changes in cardiovascular parameters in rats returned to control values by 24
      hours after exposure. In a hamster cardiomyopathy model, no adverse cardiac or
      pulmonary changes were detected after exposure to concentrated ambient PM. Thus,
      these studies found that cardiopulmonary effects could be produced in rats, but
      not in hamsters with cardiomyopathy, exposed to concentrated ambient PM. None of
      the changes occurred on every exposure day and none appeared to be life
      threatening. Thus, the cardiac changes may reflect changes in homeostasis that
      could affect individuals who are critically ill, and these findings do not
      resolve the biological plausibility of adverse health effects associated with
      ambient PM in epidemiologic studies.

PMID- 10897488
TI  - [Risks and consequences of tumor seeding after percutaneous fine needle biopsy
      four diagnosis of hepatocellular carcinoma].
AB  - A review of the literature shows that tumour seeding after fine-needle biopsy of
      a hepatocellular carcinoma is observed in 0.6 to 5.1% of cases. This complication
      may be detected between one and 72 months after needle biopsy, and the lapse of
      time between biopsy and diagnosis of recurrence is influenced neither by the
      tumour grading nor by the diametre of the needle and number of puncture. In most
      cases, needle biopsy is not necessary to establish the surgical indication and
      may compromise the result of surgery; it should therefore be restricted to
      exceptional cases. Because needle-tract seeding may be the sole tumour
      recurrence, close follow-up of patients who have undergone pre-operative needle
      biopsy is important for early detection and possible cure.

PMID- 10897489
TI  - [Stress echocardiography: analysis of results in 100 coronary angiography
      patients].
AB  - Stress echocardiography is increasingly accepted as a reliable, noninvasive
      method for assessment of coronary artery disease. We retrospectively analysed the
      results of the first 100 consecutive patients (79 males, 62 +/- 10 years), who
      had both stress echocardiography and coronary angiography within 3 months without
      intercurrent revascularisation. In 71% of the patients treadmill- was performed
      and in 29% dobutamine-stress echocardiography. No patient had severe side
      effects. In the 100 patients, positive predictive accuracy for detection of
      significant coronary artery disease was 95% and for multivessel disease 80%.
      There was no significant difference in positive predictive value for detection of
      significant stenosis in the posterior perfusion territory (left circumflex, right
      coronary artery), with 79% compared to the anterior perfusion territory (86%, p =
      ns). Sensitivity for the left circumflex (60%) tended to be lower compared to the
      right coronary artery (76%) or left anterior descending coronary artery (82%) (p
      = ns). Despite poorer echocardiographic image quality in dobutamine-stress
      echocardiography patients, there was no significant difference between treadmill-
      and dobutamine-stress echocardiography regarding the positive predictive value
      for detection of coronary artery disease (98 vs 92%) or for recognition of
      multivessel disease (79 vs 79%) (p = ns). False results of stress
      echocardiography were rare (7%): false positive results were more common in the
      presence of wall motion abnormalities at rest, false negative results after an
      insufficient stress-induced increase in heart rate. Gender or left ventricular
      hypertrophy had no impact on stress echocardiography results (p = ns). In
      conclusion, both dobutamine- and treadmill-stress echocardiography are reliable,
      sensitive methods for non-invasive assessment of coronary artery disease; this is
      also valid in women and in left ventricular hypertrophy.

PMID- 10897490
TI  - [Evaluating the efficacy and tolerance of atorvastatin in hyperlipidemia in
      general practice (SWITCH Study)].
AB  - Elevated levels of serum lipids and lipoproteins are known to play a major role
      in the development of atherosclerosis and subsequent coronary heart disease
      (CHD). In controlled clinical studies, atorvastatin (Sortis), a new 3-hydroxy-3
      methyl-glutaryl-coenzyme-A (HMG-CoA)-reductase inhibitor, proved to be a very
      effective and safe lipid-lowering agent. The aim of this open-label, multicentre
      study (without a control group) was to confirm the efficacy and safety of
      atorvastatin in a private practice group, including 181 Swiss cardiologists,
      internists, and general practitioners. A total of 877 hyperlipidaemic patients
      requiring treatment participated in this study. To evaluate the effectiveness of
      the treatment with atorvastatin over a period of 12 weeks, total plasma
      cholesterol (TC), HDL cholesterol, LDL cholesterol and triglycerides (TG) were
      determined every 4 weeks. The initial atorvastatin dose was 10 mg in 78% of
      patients and 20 mg in 22%. The dose was doubled every 4 weeks until the target
      values of TC < or = 5.2 mmol/l and TC/HDL < or = 5 were reached. After 12 weeks
      of treatment with atorvastatin the mean reduction in TC, TC/HDL, LDL and TG
      compared to baseline levels was 33, 37, 42, and 25% respectively. At the same
      time the HDL concentration was increased by 9%. These results were evidenced in
      patients with existing coronary heart disease, in high risk patients without
      manifest coronary heart disease and in patients with significantly elevated lipid
      levels (TC > 7.8 mmol/l, TC/HDL > 6.5). After treatment with atorvastatin for 12
      weeks, 59% of patients had reached the therapeutic target of TC < or = 5.2
      mmol/l. The target of TC/HDL < or = 5 was reached by 79%. Atorvastatin was almost
      without exception well tolerated, the most frequently reported side effects being
      nausea, myalgia, and headache. In this open-label multicentre study atorvastatin
      was found to be effective and well tolerated. The observed reduction in the lipid
      and lipoprotein concentration is in accordance with the results of published
      controlled studies. The lipid and lipoprotein concentrations were decreased
      significantly in patients with slight to moderate elevation of lipid levels as
      well as in those with significantly raised values.

PMID- 10897491
TI  - [R-hirudin (lepirudin, refludan) as an alternative anticoagulant in heparin
      induced thrombocytopenia during cardiopulmonary bypass connection].
AB  - A 72-year-old patient with heparin-induced thrombocytopenia (HIT) and global
      cardiac decompensation underwent cardiac surgery using an extracorporeal circuit
      (ECC). For systemic anticoagulation r-Hirudin (lepirudin, Refludan) was
      administered as a heparin substitute during extracorporeal circuit. During
      cardiopulmonary bypass (100 min) the concentration of r-Hirudin was between 2.9
      and 4.6 mcg/ml under continuous infusion of r-Hirudin at between 1.5 and 4.5
      mcg/kg/min. The operation was successful and during its course no abnormal
      bleeding or fibrin formation in the extracorporeal circuit was observed. One hour
      after operation haemorrhage occurred and rethoracotomy was performed without
      discovering the cause of the surgical bleeding. After substitution with fresh
      frozen plasma, thrombocytes and Prothromblex the bleeding stopped on the
      operation day. The further postoperative course was uncomplicated. After 3 days
      the patient came to nursing station and was discharged from hospital to a
      rehabilitation centre after 13 days. After a further 3 weeks he went home in a
      good general condition.

PMID- 10897492
TI  - [Acute dysphagia: gastroesophageal reflux disease with meat bolus in the lower
      esophagus].

PMID- 10897493
TI  - [Ernst L. Wynder, M.D., Dr. Sc. h.c. (mult.), Dr. med. h.c.--1922-1999. A
      memorial].

PMID- 10897494
TI  - [Prevalence of tobacco use in Switzerland in the 1990's--estimation of
      consumption trends based on 2 methods].
AB  - Smoking prevalence rates in Switzerland in the 1990s++ have been estimated from
      Perma data, which have been available quarterly since 1991, as well as from the
      data of the first and second Swiss Health Surveys, conducted in 1992/93 and 1997.
      Both sources--each providing data on more than 10,000 respondents--have been
      large-scale surveys that have used different but complementary survey designs.
      The probabilistic sampling design of the Health Surveys assures representative
      findings; the Perma data, although obtained through a non-probabilistic sampling
      design, permits trend analysis as Perma uses multiple measurement points and
      therefore time-series methodology can be applied. Both Perma and the Health
      Surveys yielded approximately the same prevalence of 37% male smokers in 1992/93
      and 39% in 1997. For females Perma gave 4% higher prevalence rates than the
      Health Surveys (Surveys 1992/93: 24%; 1997: 31%). For both sexes the increase in
      total smoking prevalence was accounted for mainly by adolescents and young
      adults. Whereas the Surveys showed an increase from 29% to 41% (18% to 39%) in
      males (females) aged 15 to 19 years, the corresponding increase derived from
      Perma was 50% less. Except for this youngest age-group, differences between the
      methods remained within standard statistical norms. There is no doubt, however,
      that smoking in adolescents increased between 1992/93 and 1997.

PMID- 10897496
TI  - Exercise and physical activity: an analysis of answers to an open-ended survey
      question.
AB  - In this paper 708 comments made in response to an open-ended question at the end
      of a lifestyle survey are analysed in order to explore issues in exercise
      behaviour. Quantitative and qualitative techniques are used. Five areas are
      identified as important in shaping people's exercise behaviour: 1) Health-related
      factors; 2) Factors related to available facilities; 3) Issues of behavioural
      change; 4) Issues of health information and promotion; and 5) Miscellaneous
      issues. Each of the five areas of responses is discussed and related to current
      theory on exercise behaviour. Three substantive conclusions are drawn. Firstly,
      environmental change might be important to people but not necessarily in a
      personalized way. Secondly, health problems are an important barrier to
      exercising. Thirdly, health promotion possibly targets sedentary individuals too
      much. With regard to the methodology, the open-ended question proves to yield
      interesting information. However, a single powerful factor cannot be found in the
      data and the data seems to suffer from a problem of low-explained variance.

PMID- 10897495
TI  - [Evaluation of the "future non-smokers" campaign of the Swiss Society of
      Pharmacists].
AB  - In order to promote low threshold smoking cessation, a campaign was organized by
      the Swiss Society of Pharmacists in 616 Swiss pharmacies. The evaluation of this
      project took into consideration the actual smoking cessation counselling and the
      attitudes towards the campaign and tobacco prevention of the person responsible
      for the campaign in the pharmacy. Consultations with smokers were documented in
      activity statistics one week before and throughout the six weeks of the campaign.
      The attitude was assessed by a standardized questionnaire. 32% of the
      participating pharmacies completed activity statistics, 58% participated in the
      attitude survey. Frequency of counselling was best predicted by the customer
      pattern of pharmacies. The highest frequency was observed among pharmacies with a
      majority of non regular customers. Intensity of counselling was best predicted by
      the extent of preliminary training of the pharmacy personnel. The most positive
      view towards tobacco prevention and the highest degree of interest in a future
      campaign were shown by the campaign responsibilities of pharmacies characterized
      with both frequent and intensive counselling activity. The results of this study
      show that pharmacies can play a role in offering low threshold smoking cessation
      programs. Major pre-requisites for this are motivation with regard to prevention,
      as well as continuing education of pharmacists and the pharmacy personnel.

PMID- 10897497
TI  - Parental family variables and likelihood of divorce.
AB  - It has long been established that divorced men and women have substantially
      higher standardized general mortality than same gender persons. Because the
      incidence of divorce is increasing in many countries, determinants of divorce
      rates assume great importance as indirect risk factors for several diseases and
      conditions that adversely affect health. We have undertaken a study in Athens,
      Greece, to evaluate whether sibship size, birth order, and the gender composition
      of spousal sibships are related to the probability of divorce. 358 high school
      students, aged between 15 and 17 years, satisfactorily completed anonymous
      questionnaires, indicating whether their natural parents have been separated or
      divorced, their parents' educational achievement, birth order and sibship size by
      gender. The study was analyzed as a twin case-control investigation, treating
      those divorced or separated as cases and those who were not divorced or separated
      as controls. A man who grew up as an only child was almost three times as likely
      to divorce compared to a man with siblings, and this association was highly
      significant (p approximately 0.004). There was no such evidence with respect to
      women. After controlling for sibship size, earlier born men--but not women-
      appeared to be at higher risk for divorce compared to those later born. There was
      no evidence that the gender structure of the sibship substantially affects the
      risk for divorce. Even though divorce is not an organic disease, it indirectly
      affects health as well as the social well-being. The findings of this study need
      to be replicated, but, if confirmed, they could contribute to our understanding
      of the roots of some instances of marital dysfunction.

PMID- 10897498
TI  - AIDS lessons from South Africa.

PMID- 10897499
TI  - Daybreak of AIDS epidemic in Japan.

PMID- 10897500
TI  - Case report: pemphigus vulgaris in a patient infected with HIV.

PMID- 10897502
TI  - HIV infection with negative serological tests: development of seropositivity in
      association with highly active antiretroviral therapy.
AB  - A 19-year-old woman with well-documented HIV-1 infection had persistently
      negative enzyme immunoassay (EIA) and Western blot serological tests. She has
      plasma HIV-1 RNA levels of > 480,000 copies/mL and T-helper cell counts of
      approximately 100/mm3. When treated with highly active antiretroviral therapy
      (HAART), the viral load became undetectable (< 400 copies/mL), the T-helper cell
      count increased to > 500/mm3 and EIA and Western blot tests became positive.

PMID- 10897501
TI  - Effect of HIV-1 infection on tuberculosis and fertility in a large workforce in
      Kinshasa, Democratic Republic of the Congo.
AB  - To determine the effect of an HIV counseling service on the incidence of HIV and
      tuberculosis infection and on the fertility rate in a large workforce cohort of
      adult men and women from Kinshasa, Democratic Republic of Congo (formerly Zaire),
      we conducted a 2-year prospective longitudinal cohort study, two large Kinshasa
      businesses (a commercial bank and a textile factory). We determined baseline HIV
      1 seroprevalence, HIV-1 and tuberculosis mortality/morbidity, and fertility rates
      during 24 months of follow-up on 8866 employees and 6411 wives of male employees.
      The baseline HIV-1 seroprevalence was 2.8% in male employees (n = 6657), 8.4% in
      female employees (n = 417), and 2.4% in the wives of male employees (n = 4692).
      The HIV-1 seroincidence per 100 person-years of follow-up in these three groups
      was 0.9, 0.5 and 0.8, respectively. The incidence of tuberculosis was 2.4/100
      person years in persistently seropositive individuals compared with a 0.38 rate
      in persistently seronegative individuals (p < 0.01). The annual fertility rate in
      persistently seronegative women was 250.0/1000 women compared with a rate of
      140/1000 in persistently seropositive women (p < 0.001). Forty-eight (44%) of 105
      male employees and 17 (26%) of 60 wives of male workers who died during follow-up
      were HIV-1 seropositive. HIV infection was responsible for nearly one half of all
      deaths in this large workforce. Tuberculosis incidence was six times higher in
      HIV-1-infected compared with uninfected individuals. Counseling of HIV-infected
      women and their husbands appeared to be effective as their cumulative fertility
      rate was 44% lower than the rate in similarly aged uninfected women.

PMID- 10897503
TI  - Developing a self-administered tool to predict adherence to antiretroviral
      therapy: design, method, and objectives.
AB  - Noncompliance to current antiretroviral therapy may be one of the greatest public
      health challenges associated with the management of HIV/AIDS. The public health
      consequences extend beyond an individual's health decisions, judgements, and
      responsibilities to include societal concerns and ethical considerations.
      Understanding the predictors of compliance and noncompliance to current
      antiretroviral therapies, and identifying individuals according to their expected
      compliance outcomes are important aspects associated with the successful
      management of HIV-infected individuals. The stepwise methodological approach
      utilized to develop the self-administered survey instrument predictive of
      compliance to complex antiretroviral drugs regimens and adherence to other
      medical recommendations is reported, and the implications discussed.

PMID- 10897504
TI  - Correlates of alcohol and/or drug use among HIV-infected individuals.
AB  - The purpose of this article is to describe the psychosocial factors associated
      with alcohol and/or drug (AOD) use among HIV-infected individuals. Their
      attitudes toward AOD use are also examined. Three hundred and three HIV-infected
      adults completed a survey on AOD use while waiting for their appointment at the
      largest, HIV-outpatient clinic in the Gulf South. Logistic regression showed that
      associating with others who use drugs and hospitalization for a mental illness
      were associated with current AOD use. Variables derived from the AIDS Risk
      Reduction Model that integrates elements of the Health Belief Model, efficacy
      theory, and social network theory, indicated that 14% of the sample admitted to
      having an AOD problem. Twenty-six percent of the AOD users reported that they
      have little social support to help them stop their AOD use. A disturbing finding
      was that 24% of the AOD users have actively sought help or treatment for their
      AOD problem and have not been able to find help. These patients differ
      significantly from the AOD users who could find help in that they are primarily
      African-American and 46% have been hospitalized for a mental illness.
      Motivational strategies and mental health interventions are necessary, which
      provide peer counseling and social support, factors that have been found to
      greatly influence behavior change. The intervention may also need to include
      spiritual and humor components because the vast majority of AOD users are
      interested in treatment approaches that include these two elements.

PMID- 10897505
TI  - HIV/AIDS prevention: a model for educating the inpatient psychiatric population.
AB  - Scientific and medical research in the field of HIV/AIDS prevention has recently
      moved closer to finding a vaccine and a cure. Behavior change, however, is
      currently the only available means to decrease new cases of HIV, and the proper
      use of condoms is the most effective preventative measure for people with severe
      and persistent psychiatric disabilities who are sexually active. It is now well
      documented that educating this population about safer-sex practices can reduce
      their risk of getting HIV/AIDS and other sexually transmitted diseases (STDs).
      The following article is a brief review of a model used to educate clients in an
      inpatient, state psychiatric hospital. Strategies that focus on developing
      behavioral skills are outlined.

PMID- 10897506
TI  - Public policy update. An amfAR report.

PMID- 10897507
TI  - KS trial begins.

PMID- 10897508
TI  - Gel for neuropathy studied.

PMID- 10897509
TI  - Repeat prescribing: a role for community pharmacists in controlling and
      monitoring repeat prescriptions.
AB  - BACKGROUND: Traditional systems of managing repeat prescribing have been
      criticised for their lack of clinical and administrative controls. AIM: To
      compare a community pharmacist-managed repeat prescribing system with established
      methods of managing repeat prescribing. METHOD: A randomised controlled
      intervention study (19 general medical practices, 3074 patients, 62 community
      pharmacists). Patients on repeat medication were given sufficient three-monthly
      scripts, endorsed for monthly dispensing, to last until their next clinical
      review consultation with their general practitioner (GP). The scripts were stored
      by a pharmacist of the patient's choice. Each monthly dispensing was authorised
      by the pharmacist, using a standard protocol. The cost of the drugs prescribed
      and dispensed was calculated. Data on patient outcomes were obtained from
      pharmacist-generated patient records and GP notes. RESULTS: A total of 12.4% of
      patients had compliance problems, side-effects, adverse drug reactions, or drug
      interactions identified by the pharmacist. There were significantly more problems
      identified in total in the intervention group. The total number of consultations,
      deaths, and non-elective hospital admissions was the same in both groups. Sixty
      six per cent of the study patients did not require their full quota of prescribed
      drugs, representing 18% of the total prescribed costs (estimated annual drug cost
      avoidance of 43 Pounds per patient). CONCLUSION: This system of managing repeat
      prescribing has been demonstrated to be logistically feasible, to identify
      clinical problems, and to make savings in the drugs bill.

PMID- 10897510
TI  - The economics of employing a counsellor in general practice: analysis of data
      from a randomised controlled trial.
AB  - BACKGROUND: Counselling is currently adopted in many general practices, despite
      limited evidence of clinical and cost effectiveness. AIM: To compare direct and
      indirect costs of counsellors and general practitioners (GPs) in providing care
      to people with emotional problems. METHOD: We carried out a prospective,
      randomized controlled trial of non-directive counselling and routine general
      practice care in 14 general practices in north London. Counsellors adhered to a
      Rogerian model of counselling. The counselling sessions ranged from one to 12
      sessions over 12 weeks. As reported elsewhere, there were no differences in
      clinical outcomes between the two groups. Therefore, we conducted a cost
      minimisation analysis. We present only the economic outcomes in this paper. Main
      outcome measures were cost data (service utilisation, travel, and work absence)
      at baseline, three months, and nine months. RESULTS: One hundred and thirty-six
      patients with emotional problems, mainly depression, took part. Seventy patients
      were randomised to the counsellors and 66 to the GPs. The average direct and
      indirect costs for the counsellor was 162.09 Pounds more per patient after three
      months compared with costs for the GP group; however, over the following six
      months the counsellor group was 87.00 Pounds less per patient than the GP group.
      Over the total nine-month period, the counsellor group remained more expensive
      per patient. CONCLUSIONS: Referral to counselling is no more clinically effective
      or expensive than GP care over a nine-month period in terms of direct plus
      indirect costs. However, further research is needed to establish indirect costs
      of introducing a counsellor into general practice.

PMID- 10897511
TI  - The validity of the diagnosis of depression in general practice: is using
      criteria for diagnosis as a routine the answer?
AB  - BACKGROUND: In general practice, making a diagnosis does not follow the same
      lines as in secondary care because every new diagnosis is made against
      'foreknowledge' and could be coloured by it. This could explain low accordance
      and differences in diagnoses between primary and secondary care, in particular
      when mental illness such as depression is concerned. When criteria are used for
      diagnosis there should be no differences. AIM: To establish the accordance with
      the Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV)
      criteria of major depressive disorder when the diagnosis of depression has been
      made by general practitioners (GPs) for whom coding and using criteria for
      diagnosis is a daily routine (ICHPPC-2 criteria). METHOD: Ninety-nine general
      practice patients from four general practices belonging to the Continuous
      Morbidity Registry (CMR) of the University of Nijmegen in The Netherlands were
      interviewed using the Composite International Diagnostic Interview (auto) 12
      month version (DSM-IV criteria). Thirty-three patients had a code for depression;
      33 patients a code for chronic nervous functional complaints (CNFC); and 33 had
      no code for mental illness (the depression and CNFC codes were given in the 12
      months prior to the interview). Specificity and accordance with the DSM-IV
      criteria of major depressive disorder (MDD) were calculated with the results from
      the interviews. RESULTS: Of the 33 general practice depression cases (all
      matching ICHPPC-2 criteria), 28 matched DSM-IV criteria: 26 for MDD and 2 for
      dysthymia. No cases of DSM-IV MDD were found in the control group without a code
      for a mental disorder, and seven out of 33 were found in the control group with
      the code for CNFC. CONCLUSION: The specificity of diagnosis of depression made by
      GPs in a continuous morbidity registry and the accordance with DSM-IV criteria
      are high. Using criteria for diagnosis, which is a trend, could be one of the
      solutions towards a better diagnosis. As far as the sensitivity is concerned, GPs
      should not be distracted from using criteria for the diagnosis of depression when
      a large variety of complaints is presented.

PMID- 10897512
TI  - Higher professional education for general practitioners: postal questionnaire
      survey.
AB  - BACKGROUND: There is no consensus about whether higher professional education
      (HPE) is necessary for general practitioners (GPs) to complete their vocational
      training. AIM: To investigate beliefs about the need for HPE, its funding,
      duration, curriculum, and whether new principals (NPs) are eligible to undertake
      it. METHOD: A confidential postal questionnaire was sent to senior partners, GP
      registrars, NPs, GP trainers, and GP tutors, principally in the old South West
      region of England, and nationally to other 'academic' GPs. RESULTS: Of 1199 GPs,
      750 (62.6%) replied; 561 (79.2%) responders agreed with the principle of HPE for
      NPs, especially members of the Royal College of General Practitioners and
      academic GPs; senior partners (SPs) were less likely to agree (all P < 0.001). Of
      700 GPs, 331 (50.3%) believed that HPE should last one or two years, 66.4% agreed
      that NPs should have a major input into the HPE curriculum, and 54.6% agreed that
      health authorities should be major sources of funding, together with the
      postgraduate deans (29.9%). GP tutors and trainers should have the main
      responsibility for teaching HPE. The principal barriers to setting up a HPE
      course are the financial cost, the time cost, difficulty in changing the status
      quo, and various practical problems. The facilitatory influences are: the
      enthusiasm of the NPs and of their clinical colleagues, an appropriate
      educational environment, a high quality clinical base, and recognition that NPs
      have specific needs. Of 668 GPs, 89.7% would release NPs if an HPE course were
      free and locums were paid, although SPs were less likely to agree (P < 0.001); if
      the HPE course cost the practice money, then only 30.6% would release NPs.
      CONCLUSION: If adequately externally funded, then there is widespread support for
      HPE with most GPs willing to release NPs. NPs and existing GP teachers should
      decide the curriculum. Its aim should be to provide educational support for NPs
      during the transition from GP registrar to fully-trained GP principal.

PMID- 10897513
TI  - Higher professional education for general medical practitioners: key informant
      interviews and focus group findings.
AB  - BACKGROUND: If higher professional education (HPE) for general practitioners
      (GPs) is to be implemented, then key stakeholders will need to be supportive.
      AIM: To investigate stakeholders' beliefs about the concept of HPE, its funding,
      and relationships to education and care. METHOD: Interviews were conducted using
      a topic guide with a health authority (HA) representative, the Local Medical
      Committee Chair, the Medical Audit Advisory Group Chair, a GP tutor from each of
      the six health authorities in the old South West region, and a senior member of
      the three academic GP departments and the two Royal College of General
      Practitioners faculties in the region. Focus groups were held with GP registrars
      on both vocational training schemes (VTSs) and on the one HPE course in the
      region. These were recorded, transcribed verbatim, and analysed for emergent
      themes that were triangulated with the ideas expressed in the focus groups; the
      same topic guide was used for both. RESULTS: Of 29 key informants, 24 were
      interviewed. Six focus groups were held (the one HPE group and five out of the
      nine VTSs), after which no new ideas emerged. There is a transition period, after
      becoming a new principal (NP) and before becoming a fully competent independent
      GP, during which NPs need support. Benefits would include receiving peer support
      to reduce stress during the transition, enhanced non-clinical competencies,
      becoming a better skilled GP, avoiding the negative personal impact of a career
      as a GP, and helping recruitment. To improve patient care there must be a link
      between education and service provision. Funding is the major consideration in
      setting HPE; mixed funding is best coming from top-sliced General Medical
      Services (GMS), the HA, and regional educational funds. Barriers might include
      NPs' practice workload, their enthusiasm, and their partners' attitudes. The
      other key is a local enthusiast to initiate a course and coordinate the
      'players'. The curriculum would be principally non-clinical and should be agreed
      by learners and the course tutor together, taking advice from various interested
      parties. CONCLUSION: There is a need for HPE for new NPs. It will require funding
      external to individual practices or NPs and a local enthusiast. Top-slicing of
      GMS funds is one source of funding, with additional funds from regional education
      and HAs. HPE must be related to service provision, to NP needs, and to vocational
      training.

PMID- 10897514
TI  - Organising primary health care for people with asthma: the patient's perspective.
AB  - BACKGROUND: The 1993 chronic disease management contract encourages United
      Kingdom general practices to implement a standardised package of care with an
      emphasis on regular visits to an asthma clinic. AIM: To explore the views of
      people with asthma about the organisation of asthma care in general practice.
      METHOD: Semi-structured interviews with 20 patients registered with one practice
      with a nurse-run asthma clinic. The sample was selected to provide people with a
      wide range of ages and disease severity, and included parents of children.
      RESULTS: The age range of the interviewees was five to 87 years (parents of
      children were interviewed) and half of the interviewees had attended the asthma
      clinic at some time. In describing how they managed their asthma, people
      identified their medical care alongside other important factors, such as avoiding
      smoking and pollution, and a decision to seek medical help was made in the
      context of all of life's other priorities. People expressed diverse views about
      the organisation of care, describing how their needs changed over time and how
      they balanced up several factors in deciding what was best for them. These
      factors were encompassed by four themes: the accessibility of care, severity of
      asthma and dealing with uncertainty, self-knowledge and self-management, and
      expert knowledge and therapeutic relationships. Interviewees were evenly split
      between wishing to be seen regularly in the clinic and wishing only to attend
      when needing help. CONCLUSION: Patients required asthma services that allow
      individual choice and flexibility, and eight service objectives were identified
      that would cover most people's needs.

PMID- 10897515
TI  - Evaluation of a direct doctor-patient telephone advice line in general practice.
AB  - A general practitioner-staffed direct access telephone advice line was made
      available for 30 minutes every morning at an inner-London practice to advise
      patients with urgent problems. Users valued the service, but the impact on
      surgery consultations was too small for this to be advocated as an alternative to
      emergency consultations.

PMID- 10897516
TI  - GPs' referral to mental health care during the past 25 years.
AB  - Previous research has shown that mental disorder in the community has remained
      fairly constant over the past 30 years. As a result there has been a shift in
      mental health care from primary care to specialised mental health care. This
      shift should be visible in higher referral figures from general practice. In this
      longitudinal analysis of mental health referrals (1971 to 1997), the authors
      aimed to answer whether these higher referral rates have occurred, whether there
      are increases in referral for specific groups, and whether the referral pattern
      has changed. The results demonstrate an increase in referral rate with a factor
      of 4.5. It is concluded that we are witnessing a pull from mental health care
      together with a push from general practice, thus reinforcing each other.

PMID- 10897517
TI  - Management of acute uncomplicated urinary tract infections in general practice in
      the south of The Netherlands.
AB  - There is debate about the ideal diagnostic procedure for urinary tract infections
      (UTIs) in general practice. The aim of this study was to evaluate nitrite and
      leucocyte esterase strip test procedures in general practice patients, and to
      relate the results to the decision of the general practitioner to prescribe
      antibiotic therapy. A total of 292 female patients from eight general practices
      in the Maastricht area, who were aged 12 years or over with complaints suggesting
      UTI, were included in the study. All eight practices tested fresh urine samples
      using the nitrite strip test, and seven also used the leucocyte esterase strip
      test. The positive predictive value of the nitrite test was greater than the
      leucocyte test. Antibiotic therapy was nearly always prescribed when either or
      both of these tests were positive. Bacterial culture was positive in 159 (59%)
      cases, although treatment was started in 70 (27%) cases where there was an
      absence of significant bacteruria. It was found that the choice of agent used to
      treat the patient was related to the antibiotic susceptibility of the
      uropathogens that were isolated.

PMID- 10897518
TI  - Are general practitioners able to accurately diagnose dementia and identify
      Alzheimer's disease? A comparison with an outpatient memory clinic.
AB  - Since the introduction of agents for the treatment of Alzheimer's disease, and in
      order to increase understanding of a patient's changed behaviour, it has become
      particularly important that dementia is both diagnosed at an early stage and
      differentiated into its subtypes. This study aims to ascertain whether GPs were
      able to diagnose dementia and identify the type of dementia accurately and
      confidently. GPs were well able to assess the firmness of their own dementia
      diagnoses, which supposes that they are able to make appropriate selection for
      referral. Diagnostic support from a specialised team can particularly contribute
      to identifying the type of dementia.

PMID- 10897519
TI  - General practitioner psychological management of common emotional problems (I):
      Definitions and literature review.
AB  - General practitioners' (GPs') treatment of patients with common emotional
      problems often includes some form of psychological management within the
      consultation. Such psychological management may be limited to listening and
      discussion or may also include more specific psychological approaches, such as
      use of counselling, problem-solving, or cognitive-behavioural techniques. This
      paper defines GP psychological management and reviews what is known about its
      frequency and effectiveness. MEDLINE and PsychLIT searches were undertaken of
      empirical studies of the psychological management of emotional problems by GPs in
      routine consultations published up to 1998. Thirty-six studies were identified.
      Most lacked details of the nature of the psychological management reported,
      making it difficult to compare studies. The frequency of use of psychological
      management by GPs was found to be generally less when rated by external observers
      than when assessed by GP self-report. There is preliminary evidence from a few
      studies of the clinical effectiveness of GP psychological management in routine
      consultations.

PMID- 10897520
TI  - The state of primary care in the United States of America and lessons for primary
      care groups in the United Kingdom.
AB  - The health care system of the United States of America (USA) is lavishly funded
      and those with adequate insurance usually receive excellent attention. However,
      the system is fragmented and inequitable. Health workers often find it difficult
      to separate vocational roles from business roles. Care tends to focus on the
      acute rather than the chronic, on 'episodes of illness' rather than 'person
      centred' care, on short-term fixes rather than long-term approaches, on
      scientific/technical solutions rather than discourse or the 'art of healing', and
      on individual health rather than population health. The majority of US doctors
      are trained in the 'hightech' hospital paradigm and there is no equivalent of the
      United Kingdom (UK) general practitioner (GP), who lies at the hub of a primary
      health care team (PHCT) and who is charged with taking a long-term view, co
      ordinating health care for individual patients, and acting as patient advocate
      without major conflicting financial incentives. However, primary care
      groups/trusts (PCGs) could learn from US management and training techniques, case
      management, NHS Direct equivalents, and the effects of poorly developed PHCTs.
      PCGs could develop the UK's own version of utilisation management. A cash
      limited, unified budget within an underfunded National Health Service poses
      threats to general practice. In both the USA and the UK, primary care is a
      prominent tool in new attempts at cost control. PCGs offer the opportunity of
      better integration with public health and social services, but threaten GPs' role
      as independent advocates by giving them a rationing role. Managed care has forced
      a similar role onto our US counterparts with consequent public displeasure and
      professional disillusion. UK GPs will have to steer a careful course if they are
      to avoid a similar fate.

PMID- 10897521
TI  - General practitioners' prescribing data for multiple sclerosis patients indicates
      a link with asthma.

PMID- 10897522
TI  - Incidence and management of hypoglycaemia in children.

PMID- 10897523
TI  - General practice computing.

PMID- 10897524
TI  - General practice computing.

PMID- 10897525
TI  - Snake wars.

PMID- 10897526
TI  - Muddling through in a parallel track universe.

PMID- 10897527
TI  - Communicating for better health.

PMID- 10897528
TI  - Randomised controlled trials in general practice.

PMID- 10897529
TI  - The Shipman inquiry: implications for the public's trust in doctors.

PMID- 10897530
TI  - The use of HRT in patients with breast cancer: yes, no, or sometimes?

PMID- 10897531
TI  - GP frequent attendance in Liverpool and Granada: the impact of depressive
      symptoms.
AB  - BACKGROUND: Frequent attendance in general practice increases workload and
      affects doctor-patient relationships. It is a complex phenomenon, but patients'
      psychological problems appear to be important. AIM: To assess whether frequent
      attendance is more likely to be associated with depressive symptoms than with
      physical health problems. METHOD: The study was carried out in two general
      practices: one in Liverpool and one in Granada. Subjects comprised 127 frequent
      attenders (FAs) plus 175 matched controls, stratified by age and sex. Measures
      included demographic factors, Beck Depression Inventory (BDI), self-reported
      health, and current health problems classified by ICHPPC-2 criteria. RESULTS:
      Seventy-five (59%) FAs had a BDI score > or = 13, compared with 9 (5%) controls
      (odds ratio [OR] = 26.6, 95% confidence interval [CI] = 12.4 to 56.8, P < 0.001).
      A total of 136 (78%) controls reported their health to be good or excellent,
      compared with 40 (31%) FAs (OR = 7.6, 95% CI = 4.5 to 12.7, P < 0.001).
      Respiratory problems were present in 50 (39%) FAs and 47 (27%) controls (chi 2 =
      6.992, P < 0.03). Depression rates were similar in Liverpool and Granada,
      although Liverpool subjects were less likely to report good health. On logistic
      regression, BDI status was the major predictor of frequent attendance (OR =
      17.18, 95% CI = 7.54 to 39.01). Self-reported ill health (OR = 2.67, 95% CI =
      1.40 to 5.10) and respiratory problems (OR = 2.20, 95% CI = 1.11 to 4.37) were
      also associated with frequent attendance. CONCLUSION: Depressive symptoms were
      the major predictor of frequent attendance in this study. Clinical and research
      activity should therefore concentrate on the identification and management of
      psychological problems among FAs in general practice.

PMID- 10897532
TI  - Fatal toxicity associated with antidepressant use in primary care.
AB  - BACKGROUND: New selective serotonin reuptake inhibitors (SSRIs) are perceived to
      be much safer in use than older tricyclic antidepressants (TCAs). However,
      previous assessments of association with fatal toxicity were made too soon after
      the introduction of the new drugs to permit accurate estimation. AIM: To
      determine the level of association of antidepressant drugs with fatal poisoning
      in the treatment of depression. METHOD: National data for England and Wales for
      three years (1993 to 1995) for fatal poisonings associated with antidepressants
      were obtained and, together with national primary care data on prescribing, were
      used to calculate fatality association by antidepressant drug. RESULTS: There
      were substantial variations between drugs in the level of association with fatal
      poisoning. Assuming an average treatment episode lasted three months, one
      fatality is associated with 11,800 treatment episodes of antidepressant use (95%
      CI = 11,120 to 12,580) when only single substance fatalities are considered. For
      SSRIs as a group the association was one in 411,800 (95% CI = 243,300 to 1.34
      million) and for TCAs one in 8130 (95% CI = 7650 to 8670). However, for one of
      the newer TCAs, lofepramine, the single substance fatality rate associated with
      its use was one in 233,700 (95% CI = 124,500 to 1.89 million), which is not
      statistically significantly different from the SSRIs (P = 0.35). CONCLUSIONS:
      Estimated death rates associated with specific antidepressants should be compared
      with caution because drugs may be used selectively in patients with differing
      severity of depression. The proportion of these fatalities that could be
      prevented by switching to safer antidepressants is unclear when so few deaths are
      recorded as accidental; when there is intent to do self-harm the potential for
      switching to other means is unknown. However, this approach to relative toxicity
      may remain the best available since it is unlikely that a randomised trial will
      ever be conducted with a large enough sample size to obtain experimental data.
      Fatalities from antidepressant poisoning are very rare but if safety is paramount
      then lofepramine or an SSRI are justifiable treatment choices.

PMID- 10897533
TI  - Practical aspects of conducting a pragmatic randomised trial in primary care:
      patient recruitment and outcome assessment.
AB  - BACKGROUND: Conducting a pragmatic randomised trial in primary care is often
      accompanied by practical problems. Such problems are seldom reported and may
      constitute useful lessons for researchers planning future trials. AIM: To address
      the difficulties involved in patient recruitment and to present measures to
      minimise bias during outcome assessment. METHOD: A recently conducted trial
      comparing the effects of corticosteroid injections and physiotherapy for painful
      stiff shoulder was used to illustrate problems related to patient recruitment and
      outcome assessment. RESULTS: Recruitment of patients was not without difficulties
      despite careful preparation. Recruitment was discontinued after 20 months, when
      109 of the intended 120 patients had been admitted to the trial. The shoulder
      trial mainly included patient-oriented subjective outcome measures. Subgroup
      analyses demonstrated that patient preferences might have had some influence on
      outcome. CONCLUSIONS: General practitioners might be willing or unwilling to
      participate in research for many reasons. The researcher should take these
      motivations into account when inviting physicians to take part in research.
      Strategies to enhance enrolment should be prepared before the start of the trial.
      When blinding of patients is problematic, patient preferences should be assessed
      before randomisation and their influence on the outcome studied. Although
      involving a blinded independent observer enables a more objective assessment of
      outcome, the success of blinding should be clearly evaluated.

PMID- 10897534
TI  - Health status and management of chronic non-specific abdominal complaints in
      general practice.
AB  - BACKGROUND: While chronic non-specific abdominal complaints are common in general
      practice, data on patients' perspective and management of these complaints are
      lacking. Knowledge of these data is important for the development of guidelines
      for management and assessment of the burden of chronic non-specific abdominal
      complaints on society. AIM: To draw a comprehensive picture of chronic non
      specific abdominal complaints in general practice, including volume, patients'
      perspective, and health care involvement. METHOD: In a retrospective study, 644
      patients were selected in 16 general practices. Patients and general
      practitioners (GPs) received a questionnaire regarding the nature of complaints
      and health care management during the previous 12 months. RESULTS: Overall, 619
      questionnaires were returned and 291 patients participated. Of the study
      population, 15% of patients were diagnosed as suffering from non-ulcer dyspepsia,
      39% from irritable bowel syndrome, and 45% from other abdominal complaints. Over
      50% of patients suffered from chronic non-specific abdominal complaints on a
      daily or weekly basis. In these patients, general health perception is impaired
      and above norm scores on SCL-anxiety and SCL-depression scales were recorded.
      Only 4% of patients showed complete resolution of complaints during the previous
      12 months. Fifty-two per cent of patients consulted their GP for abdominal
      complaints. Diagnostic modalities were used frequently. Medication was prescribed
      in 83% of patients with abdominal complaints. Twenty per cent of patients were
      referred to secondary or tertiary care. There was a considerable inter-doctor
      variation in the management of chronic non-specific abdominal complaints.
      CONCLUSION: Once non-specific abdominal complaints have become chronic they are
      mainly managed by the GP. The impact on patients' physiological and psychological
      well being is large. Diagnostic and therapeutic modalities are frequently used.
      Given the considerable inter-doctor variation, research into the evidence base of
      management strategies is recommended.

PMID- 10897535
TI  - GP referral to an eating disorder service: why the wide variation?
AB  - BACKGROUND: Early detection and management of patients with eating disorders is
      thought to improve prognosis, yet little is known about the factors associated
      with referral of these patients to treatment centres. AIM: To calculate general
      practitioner (GP) referral rates to a specialist eating disorder service and
      determine the association between referral rate and general practice and
      practitioner factors. METHOD: Referral rate was calculated from a database of
      routine referrals to St George's Hospital Eating Disorder Service from January
      1990 to May 1996 and correlated with practice and practitioner details obtained
      from medical directories and health authority data. RESULTS: There was a wide
      variation in referral rates. A higher referral rate was found to be associated
      with practice size, proximity to the clinic, female GPs, GPs having the MRCGP
      qualification, being United Kingdom qualified, and offering full contraceptive
      services. Fundholding was associated with lower rates of referral. CONCLUSION:
      Patients with eating disorders may be at a disadvantage in certain practices.
      Educational interventions could be targeted towards low referrals.

PMID- 10897536
TI  - GPs' attitudes towards the treatment of drug misusers.
AB  - General practitioners (GPs) are encouraged to play a major part in the care and
      treatment of drug users; however, many regularly encounter physical or verbal
      abuse and feel frustration, disappointment, and disillusionment when treating
      such patients. Furthermore, communication difficulties between doctor and patient
      and the advent of HIV serve to intensify these problems. In order to address
      these issues, a questionnaire survey was carried out to assess what proportion of
      GPs are commonly employed in the management of drug misusers, and to examine the
      attitudes towards, and knowledge of, the management of these patients. The
      results show that this group of GPs are concerned about drug misuse in their
      immediate geographic area and believe it should be detected in general practice.
      Despite this, fewer than half of the GPs felt they had adequate knowledge of the
      issues surrounding opiate misuse. This finding certainly raises the question of
      the availability of training and education in the area of drug misuse.

PMID- 10897537
TI  - Research in primary care: extent of involvement and perceived determinants among
      practitioners from one English region.
AB  - The lack of research evidence relevant to and generated by general practitioners
      (GPs) has been a concern in the context of a putative primary care-led National
      Health Service (NHS). However, very little has been published on the current
      extent or determinants of research activity among United Kingdom primary care
      doctors. We surveyed all (n = 2770) service GPs in the West Midlands Region in
      order to quantify their research involvement and to explore determinants of this.
      The response rate was 49% (n = 1351). A total of 84% of responders reported
      participating in research or audit, with 16% having initiated their own research;
      9% of GPs had been published in a peer-reviewed journal; 6% had generated
      research funding; and 3% had held a research training fellowship. The
      characteristics positively associated with initiating research included an
      involvement in teaching, having research-active partners, the availability of
      protected time, and working in a larger practice. The most commonly perceived
      barriers to undertaking research were lack of time (92%), lack of staff to
      collect data (73%), and a lack of funding (71%). In all, 41% of responders
      reported no interest in research. Overall, the extent of research activity among
      responding GPs appears to be greater than is often assumed. Recent NHS research
      and development proposals to strengthen and develop research in primary care are,
      therefore, relevant in highlighting changes to address these issues.

PMID- 10897538
TI  - What are the attitudes of general practitioners towards research?
AB  - There is an urgent need for high quality primary care research to provide a firm
      scientific basis for a primary care-led National Health Service; however,
      relatively little is known about general practitioners' (GPs') stated practices
      and attitudes towards research. This cross-sectional questionnaire study
      documents the attitudes and stated practices of general practitioners towards
      undertaking and using research. Virtually all 249 (90%) GP responders felt that
      primary care research was important, while majorities expressed interest in
      research (61%), using research to directly influence practice (68%), and an
      interest in undertaking future research (53%). Perceived priorities for future
      primary care research are chronic illness, primary care organisation, and patient
      behaviour.

PMID- 10897539
TI  - Doctors and the assessment of blood glucose testing sticks: does colour blindness
      matter?
AB  - A group of doctors with congenital colour vision deficiency (CCVD) were compared
      with a group of controls in their assessment of colour blocks in the colour range
      of a widely available blood glucose testing stick. The majority of doctors with
      CCVD agreed with controls on colour matching. However, subjects with severe CCVD
      tended to match test blocks to a wider range of options than either those with a
      less severe defect or controls. This paper discusses the implications of these
      findings.

PMID- 10897540
TI  - General practitioner psychological management of common emotional problems (II):
      A research agenda for the development of evidence-based practice.
AB  - The majority of patients with common emotional or psychological problems are
      treated solely by general practitioners (GPs). Such treatment frequently includes
      some form of psychological management within the consultation, whether limited to
      listening and discussion or involving more specific techniques. This paper sets
      out a research agenda for the development of effective approaches to GP
      psychological management. Evidence is reviewed on three core components of all
      psychological treatments: establishing a positive therapeutic relationship,
      developing a shared understanding of the problem, and promoting change in
      behaviour, thoughts or emotions. The application of these components in GP
      psychological management is outlined and methodological issues in the development
      and evaluation of GP management approaches are discussed. Since the number of
      patients with emotional problems seen by each GP is so large, the population
      effects of even small improvements in psychological management would be sizeable.

PMID- 10897541
TI  - What does it cost the patient to see the doctor?
AB  - Against a background of increasing demands on limited resources, there will be an
      emphasis on undertaking studies that relate benefits of an intervention to the
      costs that are incurred in their production. Patient costs are an important, but
      often overlooked, part of an economic exercise and include transport costs, loss
      of employment, and loss of leisure time. This paper highlights the theoretical
      difficulties inherent in deriving patient costs and suggests a pragmatic
      framework to derive unit costs in these areas. We demonstrate that these costs
      are not inconsiderable when compared with the cost of a general practitioner
      consultation.

PMID- 10897542
TI  - Examinations.

PMID- 10897543
TI  - Which method of communication do GPs prefer to use?

PMID- 10897544
TI  - (Un)deserving male impotence.

PMID- 10897545
TI  - Patient-held cancer records.

PMID- 10897546
TI  - Withdrawal syndrome after long-term treatment with tramadol.

PMID- 10897547
TI  - The leap forward.

PMID- 10897548
TI  - Stopping antihypertensive drugs in general practice.

PMID- 10897549
TI  - Stopping antihypertensive drugs in general practice.

PMID- 10897550
TI  - Childhood obesity: nursing prevention and intervention approaches are needed.

PMID- 10897551
TI  - Listening to the quiet voices of Hispanic migrant children about health.
AB  - There is a paucity of literature related to school-aged migrant children's
      perceptions of their own health. To best provide culturally competent care, more
      information is needed about migrant children's experiences. Focus-group
      methodology allowed the voices of migrant children to be heard by primary health
      care providers at a summer school program for children of migrant farm workers in
      south Georgia. Seventy-three children participated in 14 focus-group sessions.
      Six themes emerged from the data that were analyzed by using a qualitative
      software system. They are healthy behaviors, acculturation issues, environmental
      influences, health care actions, health behavior outcomes, and learning needs.
      Emerging patterns within each theme render insight about these migrant children.
      The findings suggest implications for pediatric nurses related to culturally
      competent care.

PMID- 10897552
TI  - Measurement of physical activity, exercise, and physical fitness in children:
      issues and concerns.
AB  - Data to support the type and level of physical activity that are necessary for
      health benefits in children and for later prevention of disease as adults are not
      available. This lack of information may be caused by inconsistency in terminology
      and by issues and concerns with available instruments to measure the concept. The
      purpose of this article is to address measurement issues related to physical
      activity/exercise or physical fitness in children. Implications of these issues
      for researchers and practitioners are discussed.

PMID- 10897553
TI  - Developmental problems and interactions between mothers and prematurely born
      children.
AB  - This study explored how the developmental status of 49 3-year-old prematurely
      born children related to the interactions between these children and their
      mothers. Two 2-hour observations of mother-child interactions, the Home
      Observation for Measurement of the Environment (HOME) inventory, a developmental
      assessment, and Nursing Child Assessment Teaching Scale (NCATS) were scored when
      the child was 3 years corrected age. The effects of specific developmental
      problems (cognitive, language, and attention) were examined by comparing
      subgroups with and without these problems. Children with normal IQs spent less
      time not playing and scored higher on the NCATS than children with low IQs.
      Mothers of children with normal IQs scored higher on provision of play materials
      on the HOME. The mothers of children with language concerns interacted less,
      talked less, were more negative, and scored lower on the HOME and NCATS than
      mothers of the children with normal language abilities. Children with attention
      problems were more active than children with normal attention spans. These
      findings suggest that mother-child interactions might be useful for identifying
      children at risk for developmental delay and that interventions with preschool
      children with developmental delays will probably be more effective if their
      mothers are helped to provide a more appropriate social environment.

PMID- 10897554
TI  - Linear scleroderma: a Neuman nursing perspective.
AB  - Although quite a rare pediatric disease, linear scleroderma (LS), a chronic
      disease, may leave scarring and may have devastating effects on a child and
      family. This article provides an overview of the disease, presents a case history
      of a boy with LS, and discusses how nurses and other health-team members assisted
      the child and family in managing the illness. The description of the nursing care
      is based on the Neuman systems model and on the nursing diagnoses of fear,
      disturbed self-concept, and impaired physical mobility.

PMID- 10897555
TI  - The company they keep: the influence of peer relationships on adjustment to
      cystic fibrosis during adolescence.
AB  - A grounded theory approach was used to explore the influence of peer
      relationships on adjustment to cystic fibrosis (CF) in 15 adolescents.
      Discovering the course was the core category that captured the influence of peers
      on adjustment to CF. Four subcategories were identified: (1) losing ground, (2)
      being out of the loop, (3) finding a new company of friends, (4) fighting a never
      ending battle. The downward progression of CF and increasing social interactions
      with peers with CF during hospitalization helped them learn CF was a lifelong
      disease with relentless demands. Interventions should focus on strategies for
      promoting peer support, a positive attitude, and hope to create a sense of
      belonging, social competence, and well-being.

PMID- 10897556
TI  - International nursing education: Istanbul, Turkey.
AB  - To assist Turkish nurses in reaching educational standards and goals, an
      international neonatal program was developed that would incorporate a train-the
      trainer module. The primary goal was to develop and teach a neonatal intensive
      care course while exposing identified trainers to content, theory, teaching
      strategies, and concepts. The expectations of the future trainers were to use the
      knowledge they obtained from the course to enable them to provide future neonatal
      intensive care courses and serve as experts in the field of neonatal nursing. The
      achievement of this program was a direct reflection of a collaborative effort
      between two diverse cultures with the same goal of improving quality of nursing
      care delivered to high-risk neonates. Striving for nursing care excellence means
      continuously learning and keeping pace with the newest technologies and trends.
      Turkish nurses now have one more way of maintaining current knowledge and
      professionalism.

PMID- 10897557
TI  - Pediatric asthma: a clinical management update.

PMID- 10897558
TI  - Serving children.

PMID- 10897559
TI  - Ethics of care and the empowerment of nurses.

PMID- 10897560
TI  - Perception of Jordanian male nursing students about caring for children in the
      pediatric units after graduation.
AB  - Jordan is one of the countries that witnessed a severe shortage in nursing and a
      rapid increase in the number of male nurses in the nursing workforce. Therefore,
      working in certain clinical settings resulted in failure to compensate for the
      severe shortage of nurses in other areas such as maternity and pediatrics. The
      scarcity of research in the area of male nurses, in general, and their perception
      in working in pediatric units, specifically, are the impetus of this qualitative
      study. The purpose of this study is to explore the opinions of male nursing
      students, regarding male nurses caring for children after graduation. The
      findings of this study were classified in to the following themes: communication
      issues, qualification and specialized care, social constraints, and
      characteristics of children's health care providers. The findings showed that
      gender and sociocultural issues might be the most important factors underlying
      all issues related to barriers to caring for children, as perceived by male
      nursing students. Strategies to promote and enhance the caring of children among
      male nursing students were emphasized and addressed at the administrative and
      educational levels.

PMID- 10897561
TI  - [Intrathoracic transplantation of musculocutaneous flap for chronic empyema].
AB  - We have used the musculocutaneous (MC) flap to treat 4 patients with chronic
      empyema secondary to pulmonary tuberculosis. Subjects were 4 male patients aged
      72.8 in average. The period of illness was 10 months at the shortest and 15 years
      at the longest. All of the patients had been introduced to our department after
      open drainage thoracostomy. Two patients had been performed intrathoracic
      transplantation of the pedicled omentum flaps, however infection had been
      recurred and one patient had been carried out abdominal surgery, thus in whom the
      omentum flap couldn't be used. Intrathoracic transplantation of two latissimus
      dorsi musculocutaneous flaps and two rectus abdominis musculocutaneous flaps were
      carried out. After the radical operations, their refractory infected empyemas
      were completely healed. The MC flap was shown to be useful as a radical operation
      for severe chronic empyema, especially for the case in which the omentum flap
      can't be used.

PMID- 10897562
TI  - [Heart transplantation; restarted in Japan].
AB  - The first heart transplantation after organ transplantation law was successfully
      carried out in February, 1999 in Japan. The case was a male patient with dilated
      phase of hypertrophic cardiomyopathy and had been supported by implantable left
      ventricular assist device for 4 months. The procurement of the heart was done at
      distant place and transportation required about 2 hours by helicopter. The
      operation was done uneventfully using Lower-Shumway method and the patient was
      discharged 75 days later and has returned to the previous work at 1 year follow
      up.

PMID- 10897563
TI  - [Surgical results of the Senning operation and arterial switch operation for
      complete transposition of the great arteries].
AB  - From March 1980 to August 1997, 42 patients with complete transposition of the
      great arteries (TGA) type I and II underwent arterial switch procedure (n = 20)
      or Senning (n = 22) procedure in our institution. In arterial switch procedure
      group, there were two operative death. No late death occurred, and one patient
      underwent reoperation and one underwent balloon pulmonary angioplasty for right
      sided obstruction. The freedom from the intervention rate for right sided
      obstruction was 83.0% at 5 years, subsequently. In Senning procedure group,
      operative death occurred in two patients with TGA type II, and one patient with
      TGA type II and two patients with type I died because of cardiac events in the
      late stage. In this group, two patients died from accident. The survival rate
      excluding accidental deaths was 77.7% and 77.7% at 5 and 10 years, respectively.
      However, those patients who died in the late stage had severe pre-operative and
      post-operative complication. In conclusion, mid-term results of arterial switch
      procedure is satisfactory, however, reintervention rate was not so low. Long term
      results of Senning procedure without preoperative or postoperative complication
      was satisfactory.

PMID- 10897564
TI  - [A case of aconitine poisoning saved with cardiopulmonary bypass].
AB  - "Torikabuto" is a kind of plant which contains deadly poison. Its ingredient is
      aconitine alkaloids. We report a case of aconitine poisoning with fatal
      arrhythmia and acute pulmonary edema who was saved with cardio pulmonary bypass.
      A 41-year-old male ate to mistake "Torikabuto" for wild plant. He developed
      symptoms of dysarthria and admitted to our hospital. He developed ventricular
      tachycardia and fibrillation soon after his admission. Then he developed
      cardiogenic shock. He was resuscitated and supported with a percutaneous cardio
      pulmonary bypass. Ventricular tachycardia disappeared 24 hours after admittion.
      About 1 week later, cardio pulmonary bypass was terminated and about 3 months
      later, he discharged from our hospital.

PMID- 10897565
TI  - [A resected case of large cell neuroendocrine carcinoma].
AB  - Large cell neuroendocrine carcinoma (LCNEC) is a rare lung cancer and it has a
      poor prognosis. We describe our experience with a patient in whom LCNEC was
      diagnosed. 38-year-old woman who complained of a cough and low grade fever up was
      admitted to our hospital. Chest X-ray and CT shoued 6.5 x 5.0 mass in rt-S1 and
      S2. It was suspected as LCNEC of the right lung because of broncopscopic
      cytology. The upper lobectomy of the right lung and desection of mediastinal
      lymph nodes were performed. Pathological diagnosis was III B (T2N2M0) LCNEC. Four
      weeks after the operation, one cycle of chemotherapy (CDDP + VP - 16 + VDS) and
      one cycle of chemoradiotherapy (thoracic radiation of 40 Gy, CDDP + 5 - FU) were
      performed. There are no findings of tumor recurrence 7 months after operation.

PMID- 10897566
TI  - [Clinical evaluation of hepatic blood flow and oxygen metabolism during
      thoracoabdominal aortic surgery using pulse dye-densitometry combined with
      hepatic venous oxygen saturation].
AB  - OBJECTIVE: There has been no report that pulse dye-densitometry (PDD), a novel
      non-invasive modality for monitoring hepatic blood flow (HBF), was applied during
      cardio-pulmonary bypass (CPB). We investigated weather PDD was useful to measure
      HBF during thoracoabdominal aortic surgery using partial CPB. Furthermore, HBF
      and hepatic metabolism were assessed during selective visceral perfusion or shunt
      using PDD, hepatic venous oxygen saturation (ShO2), and analysis of hepatic
      metabolic products. METHODS: A prospective study was carried out in eight
      patients who underwent thoracoabdominal aortic surgery from April 1998 to October
      1999. Operative adjuncts were partial CPB with mild hypothermia in six (femoral
      veno-arterial bypass: FF group) and deep hypothermic circulatory arrest in two
      (DHCA group). Measurements were performed at following five time points; just
      before initiating CPB, just after establishing CPB, during selective visceral
      perfusion, during selective visceral shunt, and just after weaning CPB. RESULTS:
      Plasma clearance rate of indocyanine green measured by PDD well correlated with
      that obtained by in vitro spectrophotometry (p < 0.0001, R2 = 0.644). PDD
      demonstrated that decreased IIBF during selective visceral perfusion or shunt was
      well compensated by increased hepatic oxygen extraction rate in FF group and
      reduced oxygen consumption in DHCA group. Lactic acid extraction ratio and
      arterial ketone body ratio also decreased during this period. ShO2 during
      selective visceral shunt correlated with systemic systolic arterial pressure
      (SAP), and it showed a marked decrease under 20% when SAP was below 80 mmHg.
      Postoperative time course of serum total bilirubin and alanine aminotransferase
      of almost patients were within acceptable limits except the patient who required
      large amount of homologous blood transfusion. CONCLUSIONS: PDD proved to be a
      useful modality that enabled non-invasive monitoring of HBF even during partial
      CPB. Decreased HBF during selective visceral perfusion or shunt in
      thoracoabdominal aortic surgery was within physiological compensation, which led
      us conclude that it might be effective adjuncts, for visceral organ protection.

PMID- 10897567
TI  - [MVP for MR associated with extensive calcification of the mitral valve annulus].
AB  - We experienced two surgical cases of MR associated with extensive calcification
      of the mitral valve annulus. For two cases we performed MVP which consisted of
      valve repair and annular remodeling. Annular remodeling was performed only on the
      annulus without calcification using 3 mm Gore-tex graft, because calcified
      annulus did not contribute to annular dilatation and would not dilate in the
      future. Both patients recovered uneventfully. Postoperative echocardiography
      revealed no MR in both cases.

PMID- 10897568
TI  - [Four cases of third time operation of coronary artery bypass grafting].
AB  - Reoperative coronary artery bypass operations are increasing in frequency.
      Consequently, an ever-increasing pool of patients now is being seen with need of
      coronary revascularization for repeated time. Four cases of second reoperation
      were retrospectively investigated. Until March 1999, 2,563 cases of isolated
      coronary artery bypass grafting were done at the Heart Institute of Japan, Tokyo
      Women's Medical University, Tokyo, Japan. Within those cases, 124 cases (4.8%)
      were reoperated. And among those 124 cases, 4 cases (3.2%) were secondly
      reoperated. There were one hospital death and two had a perioperative myocardial
      infarction. All of them needed intraaortic balloon pump support after operation.
      Three were discharged with relief of the symptoms. The average age at the primary
      operation was 51.1 years. All these cases, at the primary operation, no ITA graft
      was used. Two cases were incompletely revascularized, because of coronary
      arteries were ungraftable. Both at reoperation and at second reoperation, we are
      trying to make a complete revascularization by all arterial grafts. But because
      of limited number of arterial graft at repeated operation, all arterial complete
      revascularization is not done without difficulty. Therefore it is concluded that
      saphenous vein graft is still needed at repeated operation.

PMID- 10897569
TI  - [Hepatic function after surgical repair of constrictive pericarditis].
AB  - We report the results of long-term follow up in 9 patients who underwent
      pericardiectomy for constrictive pericarditis. In order to test whether if
      congestive liver dysfunction due to the disease could be reversible or not after
      the surgical repair, the patients were evaluated by indocyanine green (ICG)
      clearance test. All the patients improved in NYHA classification after long-term
      periods following surgical repairs. The percentage of ICG retention at 15 minutes
      (ICG-R15) improved in most of the patients. However, two patients who had a long
      history from the onset before surgery became worse in ICG-R15. From the above
      reports, reversibility of hepatic function might be dependent on the duration of
      liver congestion before surgical repairs.

PMID- 10897570
TI  - [Thoracoscopic surgery for pulmonary nodules in patients with previous malignant
      tumor].
AB  - We evaluated the clinico-pathological characteristics of thirty-four cases with
      previous malignant tumor who was operated under thoracoscopy for pulmonary
      nodules. In twenty-three cases (67.6%), including 20 cases suspected metastatic
      pulmonary tumor before operation, thoracoscopic surgery was performed without
      doing the preoperative examinations for the definite diagnosis. The mean diameter
      of resected tumors was 13.5 mm and the definite diagnosis was determined in all
      cases by the intraoperative pathological diagnosis. There were 26(76.5%) cases of
      malignancy, including 20 cases(58.8%) of metastatic pulmonary tumor and 6 cases
      (17.7%) of primary lung cancer. Accuracy rate of predictive diagnosis before
      operation was 67.6%. From the analysis of difference between pre- and post
      operative diagnoses, inflammatory nodules or tuberculoma in the solitary nodule
      and intrapulmonary lymph nodes or silicotic nodules in the multiple nodules
      should have been considered with more carefully attention. Univariate and
      multivariate analysis showed that patients with metastatic tumor previously was
      only a predictive factor for metastatic tumor. Age, gender, CT findings, the
      number of nodules, disease free interval and tumor markers were unreliable
      factors in this study. In conclusion, there were a lot of cases with previous
      malignant tumor in which thoracoscopic surgery could become a first choice of
      modalities for the diagnosis of pulmonary nodules. Early thoracoscopic procedure
      will be recommended for such patients to perform the immediate treatment.

PMID- 10897571
TI  - [MRSA septicemia caused by an infected pacemaker lead: a case report with a
      review of Japanese literatures].
AB  - A 50-year-old woman was admitted to our hospital because of MRSA septicemia
      caused by a contaminated permanent pacemaker lead. A pacemaker system was
      successfully removed under cardiopulmonary bypass support. Postoperative
      antibiotics was administered for 7 weeks. Total removal of a pacemaker system
      under cardiopulmonary bypass support is the treatment of choice in a case with
      pacemaker infection associated with MRSA septicemia.

PMID- 10897572
TI  - [A case of aneurysm of the ductus arteriosus in the adult].
AB  - Aneurysm of the ductus arteriosus in the adults is rare. A 60-year-old male with
      no symptoms was admitted to our hospital. 3 D-CT scans and aortograms indicated a
      diagnosis of aneurysm of the ductus arteriosus. Operation was done through median
      sternotomy with the aid of partial cardiopulmonary bypass. The saccular aneurysm
      was located between the aortic isthmus and the left pulmonary artery. The
      aneurysm was resected and closed a patch. The post-operative course was
      uneventful.

PMID- 10897573
TI  - [Aortic valve replacement for aortic valve stenosis due to congenital bicuspid
      aortic valve with abnormal positioning of coronary orifice, pseudotendon, and
      persistent left superior vena cava, report of a case].
AB  - A patient was a 65-year-old female who had a complaint of palpitation was
      diagnosed aortic valve stenosis due to congenital bicuspid aortic valve with
      pseudotendon by the echocardiographic examination. We suspected left single
      coronary artery by the aortography and the coronary artery angiography. Aortic
      valve replacement and resection of pseudotendon was performed with Carbomedics
      supra-annular aortic valve (21 A). During surgery, persistent left superior vena
      cava was detected. High-posterior take-off right coronary artery was casually
      detected at aortic closure. Ventricular fibrillation due to insufficient supply
      of cardioplegic solution at right coronary area frequently occurred after cardio
      pulmonary bypass and percutaneous cardiopulmonary support was required. The
      patient was discharged 32 days after the operation. Preoperative and
      intraoperative evaluation was important in the case of aortic valvular disease.

PMID- 10897574
TI  - [Surgical treatment for infective endocarditis with multiple embolic
      complications].
AB  - A 59-year-old man was transferred to our hospital because of severe right leg
      pain, dyspnea and anuria. Due to severe cyanosis of the legs below the knees and
      severe hyperkalemia, he had undergone embolectomy of the right femoral artery and
      hemodialysis. Medical treatment for infective endocarditis was started after the
      first operation, because transesophageal echo cardiography revealed severe aortic
      regurgitation and massive vegetation of the aortic valve. Amputation of the right
      leg below the knee and of the left leg below the Lisfranc joint was performed
      after 19 days and aortic valve replacement with patch closure of a perivalvular
      abscess was performed one month after the first operation. The post-operative
      course was uneventful. He was weaned from hemodialysis and the follow-up
      echocardiographic study revealed no vegetation.

PMID- 10897575
TI  - [A case of adenoid cystic carcinoma of the trachea resected surgically after Nd
      YAG laser therapy].
AB  - A case of primary tracheal tumor ablated by endoscopic Nd-YAG laser prior to
      tracheal sleeve resection was reported. A 53-year-old man had dry cough, bloody
      sputum and dyspnea. Bronchoscopic examination revealed polypoid tumor which
      located 2 cm below the vocal cords and obstructed the airway almost completely.
      After tumor vaporized by Nd-YAG laser, bronchoscopy type 200 could pass through
      the tracheal lumen and the length of the lesion was diagnosed within 4 cm. Biopsy
      specimen was confirmed adenoid cystic carcinoma. Cervical trachea was resected of
      six tracheal cartilage (first to sixth cartilage) combined with left thyroid lobe
      under collar incision and median sternotomy. The neck was fixed for ten days by
      tying the jaw to the anterior chest wall in order to reduce excessive tension to
      the anastomosis. Pathological examination revealed the tumor residual
      microscopically, 60 Gy of radiotherapy was conducted.

PMID- 10897576
TI  - [A case of malignant fibrous histiocytoma of the chest wall].
AB  - A case of malignant fibrous histiocytoma of the chest wall. A 56-year old man was
      admitted to the hospital with a complaint of showing abnormal shadow on chest X
      ray. Chest X-ray and chest CT scan showed a calcified tumor of the chest wall.
      Histological diagnosis could not be made prior to the operation. Wide resection
      of the right chest wall containing the tumor and partial resection of the right
      lung were done. Malignant fibrous histiocytoma (MFH) showing a striform
      pleomorfic pattern was recognized histologically with resected specimen. MFH
      commonly arises in the soft tissues of the extremities, but rarely in those of
      the chest. This paper also presents a review of 38 reported cases of MFH
      originated from the chest wall.

PMID- 10897577
TI  - [A case of the cancer of an unknown primary site with elevated titer of serum CEA
      which was followed by the right sleeve upper lobectomy and mediastinal lymph node
      dissection].
AB  - A 63-year-old man was admitted because of right pneumothorax. As serum CEA
      revealed high titer, we underwent further evaluation, but we were not unable to
      find any lesion except mediastinal and hilar lymph node swelling. Though we
      performed sleeve resection of right upper lobe and mediastinal lymph node
      dissection, we were not unable to find primary lesion. But serum CEA was reduced
      markedly after surgery and we are not able to find the apparent primary site
      after that.

PMID- 10897578
TI  - [The vanishing testis: diagnosis and histological findings].
AB  - PURPOSE: Controversy exists on how to diagnose the vanishing testis and the
      degree of investigation required. In this series, we reviewed anatomical and
      histological findings in vanishing testes and investigated the effectiveness of
      diagnostic laparoscopy and imaging studies. MATERIALS AND METHODS: Between 1974
      and March 1999, 107 boys with nonpalpable testis underwent surgery. Of the total,
      52 had spermatic vessels, vas deferens, and/or nubbin, and as a result the
      diagnosis of vanishing testis was made. RESULTS: The affected side of vanishing
      testis was left 41, right 9 and bilateral 2.35 nubbins were found and the lengths
      of 24 nubbins were 5 mm or less. Histological examinations were performed in 43
      cases including 27 nubbins. From that total, 31 had vas deferens and 11 had
      epididymis. Only two nubbins had seminiferous tubules but they included no germ
      cells. The two nubbins were greater than 5 mm long. Laparoscopic surgery was
      undertaken in 12 separate cases of the vanishing testis and as a result
      hypoplastic spermatic vessels were present in 7 of the 12 cases. CONCLUSION: The
      incidence of viable testicular tissue in vanishing testes was 4.7% in our series
      and it ranges from 0-16% in other series. We submit that one can diagnose the
      inguinal vanishing testis with preoperative imaging and laparoscopy, and that the
      nubbin seldom contains testicular tissue. Our results do not support the
      necessity to remove nubbins.

PMID- 10897579
TI  - [Bone fracture receiving LH-RH agonists for prostatic cancer].
AB  - BACKGROUND: Luteinizing hormone-releasing hormone (LHRH) agonists are popularly
      used drugs in the treatment of prostatic cancer. However, it has been reported
      that continuation of a low testosterone level following a longterm administration
      of these drugs reduces the bone mineral density and makes for osteoporosis, which
      is accountable for fracture, we measured the bone mineral density and bone
      metabolic markers in the cases who suffered fracture receiving LHRH agonists for
      prostatic cancer. PATIENTS AND METHODS: Between 1994 and 1998, 196 patients (mean
      age 78.1 years) were treated with LHRH agonists for prostatic cancer. Of these
      patients, 13(7%) who had bone fracture during treated with LHRH agonists were
      divided into fracture group, and 70 patients who had not bone fracture divided
      into non-fracture group. Fracture by traffic accident was excluded. The bone
      density in the third lumbar vertebra was measured using quantitative computed
      tomography (QCT). Osteocalcin, 1, 25- (OH)2 vitamin D, urinary type 1 collagen
      cross-linked N-telopeptides (NTx), parathyroid hormone (PTH) and calcitonin were
      measured as bone metabolic markers. RESULTS: The mean age of fractured cases was
      78 years. The period from the start of treatment to fracture was 11 to 45 months
      (mean 27 months). No case of fracture at the site of metastasis of prostatic
      cancer was found. The bone density was significantly low in the fracture group
      compared with that of non-fracture group. Of the bone metabolic markers, NTx
      showed high values in the fracture group. CONCLUSION: There is a need to measure
      bone mineral density and bone metabolic markers periodically and to evaluate
      secondary osteoporosis in the patients receiving LHRH agonists for prostatic
      cancer.

PMID- 10897580
TI  - [Determinations of oxalate in urine and plasma by capillary electrophoresis].
AB  - PURPOSE: The determinations of oxalate in urine and plasma are important in the
      evaluation and treatment of patients with calcium oxalate nephrolithiasis.
      Although many analytical methods for determining oxalate have been developed,
      most of them need complicated sample preparation, and are expensive for routine
      examination. Especially for estimation of plasma oxalate, much more sensitive
      measurement is required because of the extremely low concentration. A simple and
      rapid assay for oxalate in urine and plasma by capillary electrophoresis has been
      described here, and utilized for assessment of renal oxalate clearance. In
      addition, simultaneous determination of urinary oxalate and citrate was
      developed. METHODS: A Waters Quanta 4000E system was used with a detection at 185
      nm. Separation was obtained on a fused silica capillary, 60 cm long x 75 microns
      and 100 microns (i.d.) for urine and plasma samples respectively. Urine samples
      were diluted with 60 mM hydrochloric acid, and ultrafiltrates of plasma were
      acidified and diluted with 300 mM boric acid and 50 mM phosphoric acid. RESULTS:
      The intraassay coefficient variation was 2.7-4.0% for urinary oxalate, and 1.3
      3.9% for citrate. The mean recovery ratio of 0.2 mM oxalate and 1.0 mM citrate
      added to 10 samples were 99.0% (92.6-107.4%) and 98.4% (91.2-103.9%),
      respectively. In the determination of plasma oxalate, the minimum detectable
      limit was 0.9 microM, the coefficient variation was 5.8-16.0%, and the recovery
      rate was 101.5% (87.8-125.6%). The plasma oxalate levels in 8 adult males were
      2.39 +/- 1.46 microM (Mean +/- SD). Renal oxalate clearances with one hour method
      were 72.9 +/- 20.0 ml/min in 6 healthy controls and 83.2 +/- 27.8 ml/min in 8
      stone formers. Oxalate/creatinine clearance ratios in each groups were 0.70 +/-
      0.16 and 1.11 +/- 0.34 respectively. CONCLUSION: The simultaneous determination
      of urinary oxalate and citrate was satisfactory. Capillary electrophoresis is
      suited for routine examination of urinary oxalate and citrate with the advantage
      on simplicity and economy. The assay of plasma oxalate by this method was also
      acceptably sensitive, specific under a low temperature and an acidification.

PMID- 10897581
TI  - [Changes in liver function induced by flutamide in patients with prostate cancer
      (studies in patients treated with total androgen blockage)].
AB  - OBJECTIVES: The incidence of flutamide-induced liver toxicity was studied in 30
      consecutive patients with prostate cancer who were treated with total androgen
      blockage (TAB) therapy (luteinizing hormone releasing hormone [LHRH] analogue and
      flutamide) in our hospital during the last 3 years and in 20 consecutive patients
      with prostate cancer who were treated by partial androgen blockage (PAB) therapy
      (LHRH analogue alone). METHODS: Liver function test, including measurement of
      serum levels of aspartate aminotransferase (AST) alanine aminotransferase (ALT),
      total cholesterol, total bilirubin, gamma-glutamyl transpeptidase (gamma-GTP),
      and cholinesterase were performed at regular interval. RESULTS: The incidence of
      liver toxicity in patients receiving TAB (10 cases of 25 patients) was
      significantly higher than in patients receiving PAB (2 of 18 patients). Two
      patients in whom severe liver toxicity developed after receiving TAB were
      hospitalized. However, after flutamide was discontinued all patients with liver
      damage recovered with normalization of AST and ALT levels. Levels of total
      cholesterol and gamma-GTP did not differ significantly in either patient group.
      In two patients receiving TAB total bilirubin levels showed slight, transient
      elevations after maximum elevations of AST and ALT. In 80% of patients receiving
      TAB serum levels of cholinesterase were significantly higher than those in
      patients receiving PAB. CONCLUSION: These data suggest that the risk of flutamide
      induced liver toxicity is significant in patients receiving TAB. However, this
      damage can be normalized after flutamide has been discontinued. Serum levels of
      cholinesterase also increase significantly in patients receiving TAB. This
      previously unreported phenomenon suggests an unknown effect of flutamide on liver
      function in patients with prostate cancer.

PMID- 10897582
TI  - [A case of Collet-Sicard syndrome caused by skull base metastasis of prostate
      carcinoma].
AB  - A case of Collet-Sicard Syndrome caused by skull base metastasis of prostate
      carcinoma is reported. A fifty-five years old man presenting multiple lymph node
      and bone metastases of prostate carcinoma was treated with LH-RH agonist and
      Flutamide, which induced transient decrease in serum PSA levels and size of lymph
      node metastases. After 8 months of the treatment, the patient started complaining
      headache, dysphagia and dysarthria. Brain CT and MRI demonstrated a soft tissue
      mass replacing left pyramidal bone and occipital bone around left jugular
      foramen. The tumor was diagnosed as skull base metastasis of the prostate
      carcinoma and was treated with 50Gy of radiation. The symptom improved after the
      radiation but died of the disease in 4 months. The autopsy revealed the skull
      base metastasis of the prostate carcinoma and the tumor was proved to be poorly
      differentiated adenocarcinoma, which was positively stained by anti-PSA antibody.
      The case showed cranial nerve palsy of IX to XII, which is usually called Collet
      Sicard syndrome. This is the third case report of Collet-Sicard syndrome caused
      by the skull base metastasis of prostate carcinoma, and it is the first case in
      Japan.

PMID- 10897583
TI  - [Two case reports of unilateral adrenal hyperplasia with contralateral renal cell
      carcinoma].
AB  - We report two cases of unilateral adrenal hyperplasia with contralateral renal
      cell carcinoma. First case was a 66-year-old man with right renal mass who came
      to our hospital for study. Although no major symptoms were complained, blood
      pressure was consistently above normal. Hypokalemia, low plasma renin activity
      and high plasma aldosterone level were detected. CT revealed that he had a right
      renal mass and a left adrenal tumor. Preoperative diagnosis was right renal tumor
      and primary aldosteronism due to left adrenal adenoma. Second case was a 59-year
      old man with right renal mass who also came to our hospital for study. He also
      had a left adrenal tumor, however his blood pressure was normal and serum
      hormonal analysis showed normal adrenal cortical function. Preoperative diagnosis
      was right renal tumor and non-functional left adrenal adenoma. Two patients were
      performed right radical nephrectomy with contralateral adrenarectomy.
      Pathological diagnosis were right renal cell carcinoma and left adrenocortical
      hyperplasia. One Patient clinically showed primary aldosteronism and the other
      had no clinical symptoms. These patients were rare cases with unilateral adrenal
      hyperplasia.

PMID- 10897584
TI  - [Effects of calcium on HPV16 gene transcription in cultured laryngeal epithelial
      cells].
AB  - Human papillomavirus (HPV) gene transcription is closely linked to the
      differentiation status of infected epithelial cells. A variety of physiological
      agents, including calcium, regulates the differentiation of cultured epithelial
      cells. The expression of cytokeratin No.13 (CK13) can be used as a marker for
      differentiation in cultured laryngeal epithelial cells (HLEC cells). The purpose
      of this study is to examine the effects of calcium on CK13 expression and HPV16
      gene transcription in HLEC cells. We analyzed two types of HPV16-containing HLEC
      cells: HPV 16-immortalized HLEC cells (HLEC16 cells) and HPV16-positive
      (infected) cultured laryngeal papilloma cells (HLP16 cells). In the HLEC16 cells,
      the viral genes were integrated into the host cell chromosomes, while the HLP16
      cells contained extra-chromosomal viral genes. The effects of increasing calcium
      concentrations on CK13 expression were then evaluated using immunocytochemistry.
      Both the HLP16 and the HLEC16 cells responded to an increased calcium
      concentration by inducing CK13 expression. In HLP16 and HLEC16 cells, the CK13
      expression was undetectable at low calcium concentrations (0.1 mM) but became
      clearly detectable at high calcium concentrations (1.0 mM). The level of viral
      RNA was elevated in HLP16 cells with added calcium (1.0 mM) but was similar in
      HLEC16 cells grown in either low (0.1 mM) or high (1.0 mM) calcium
      concentrations. These results suggest that a calcium-induced differentiation
      results in the up-regulation of HPV16 gene transcription in HLP16 cells. The
      integration of viral gene into the host cell chromosomes may be an important
      determinant for the differentiation-independent transcription of HPV16 genes.

PMID- 10897585
TI  - [Usefulness of the urea method in nasal discharge analysis].
AB  - We examined urea used as a dilution marker of broncho-alveolar lavage fluid to
      determine whether it was also useful as a dilution marker of nasal lavage fluid.
      We measured the concentration of urea in nasal secretions and peripheral blood
      for 91 cases. As a comparison, we also measured the total protein and albumin in
      nasal secretions and peripheral blood. The urea concentrations in nasal
      secretions were strongly correlated with that in peripheral blood (coefficient of
      correlation 0.925). The urea concentration in nasal secretions was approximately
      2.4 times higher than the level in peripheral blood. No correlation was observed
      between total protein or albumin levels in nasal secretions and those in
      peripheral blood. In two patients with Japanese cedar pollinosis, we measured
      histamine concentration in nasal lavage fluid. Although no change in histamine
      concentration was observed by direct measurement, after the values were corrected
      for urea level, an increase in histamine was clearly observed during the cedar
      pollen season. The urea method was found to be useful as a dilution marker for
      nasal lavage fluid.

PMID- 10897586
TI  - [Forecast of total pollen counts of sugi (Cryptomeria japonica) from the amount
      of male flower development and the revised total pollen counts].
AB  - We have successfully forecast the total pollen counts of sugi (Cryptomeria
      japonica) since 1996 by the amount of male flower development. The amount of male
      flower development was observed at 11 forests in the Tanba Mountains and 10
      forests in the Chugoku Mountains depending on both in Hyogo Prefecture. The
      amount of male flower development on each tree was assigned to one of five
      classes by the number of male flowers per spring. After a large harvest of male
      flowers, the production of male flowers declined in the following years,
      especially at high altitudes. It was also followed by a decrease in the number of
      airborne pollen grains in the later pollen season. According to an analysis of
      weather conditions, total pollen counts were correlated with the high temperature
      between July 6 and 20 and the total pollen counts of the previous season.
      However, the amount of male flower development was the most significant indicator
      for forecasting total pollen counts. Decrease in total pollen counts due to
      abnormal weather during the pollen season was correlated with discrepancies in
      forest flowering time according to observations made in the Rokko Mountains.
      Increase in total pollen counts was connected by a development of the sugi forest
      areas. Twenty percent of mature sugi forests from 1992 which showed an annual
      increase were associated with an increase in total pollen counts. The accuracy of
      the forecast was improved by revising the total pollen counts for weather
      conditions during the dispersion stage, a decrease in the production of male
      flowers at high altitude, and an increase in the production of male flowers
      connected by a developing forest areas.

PMID- 10897587
TI  - [Three-dimensional analysis of eye movements induced by roll and pitch tilt].
AB  - The torsional eye movements induced by the right and left ear-down position are
      known as "ocular counter-rolling" but the mechanism of the horizontal and
      vertical eye movements has not been clarified. The vertical eye movements induced
      by backward tilt are known as the "doll reflex", but clear eye movements are
      induced by forward tilt. The mechanism of horizontal and torsional eye movements
      are unclear. To detect 3D eye movements in the roll and pitch planes, we
      performed 3D analysis of eye movements by our video-oculographic method. During
      roll tilt, counter-torsional eye movements were clearly induced, but no definite,
      eye movements were observed in the horizontal and vertical components of eye
      movements. During pitch tilt, downward eye movements were observed following
      backward tilt, but no clear eye movements were observed following forward tilt.
      Moreover, no clear horizontal or torsional eye movements were observed during
      pitch tilt. These results suggest that the response to pitch tilt depends on the
      saccular input.

PMID- 10897589
TI  - [Prognostic factors in non-Hodgkin's lymphoma of Waldeyer's ring and the lymph
      nodes of the neck].
AB  - Prognostic factors and treatment outcome of 74 patients with non-Hodgkin's
      lymphoma of Waldeyer's ring (male 34, female 16, median age 63 years) and
      cervical lymph nodes (male 17, female 7, median age 62 years) were analyzed
      retrospectively. The prognostic factors analyzed were: age, B-symptoms, serum LDH
      levels, and Ann Arbor stage. We also analysed the TNM classification (1987) of
      Waldeyer's ring lymphoma (previously referred as nasopharyngeal and oropharyngeal
      cancer) as a new prognostic factor. The 5-year-survival rate of the patients with
      Waldeyer's ring non-Hodgkin's lymphoma was 67%, compared with 34% for cervical
      lymph node lymphoma. In univariate analyses, unfavorable outcome was associated
      with age (age > 60 years), B-symptoms, elevated serum LDH level, and stage.
      Multivariate analysis showed that age and elevated serum LDH level were
      significant independent risk factors for death. The 5-year-survival rate
      according to TNM classification of Waldeyer's ring lymphoma was: T1 (4 cases)
      75%, T2 (23 cases) 83%, T3 (10 cases) 56%, T4 (4 cases) 0%; according to N stage,
      N0 (15 cases) 91%, N1 (7 cases) 73%, N2 (11 cases) 55%, N3 (5 cases), M1 (3
      cases) 0%, and according to TNM stage, stage I (one case) stage II (9 cases)
      100%, stage III (12 cases) 80%, stage IV (19 cases) 34%. These results suggest
      that the N classification of Waldeyer's ring non-Hodgkin's lymphoma may be a new
      prognostic factor.

PMID- 10897588
TI  - [Value of upper gastrointestinal endoscopic examination of head and neck cancer
      patients].
AB  - Between January 1995 and March 1999, we performed the upper gastrointestinal
      endoscopic examinations on 287 patients with head and neck cancers and detected
      23 cases (8%) of esophageal cancer and 8 cases (2.8%) of gastric cancer, showing
      how frequently esophageal cancer occurs in head and neck cancer. The esophageal
      cancer involved the oral cavity in 8 cases (9.5%), the oropharynx in 3 cases
      (8.6%), the hypopharynx in 10 cases (19.6%), and the larynx in 2 cases (2%).
      Esophageal cancer occurred most frequently in hypopharyngeal cancer, particularly
      the pyriform sinus type and the postcricoid type. We conclude that upper
      gastrointestinal endoscopic examination, including Lugol staining, is necessary
      in head and neck cancer patients.

PMID- 10897590
TI  - [Autotransplantation of ectopic lingual thyroid--a case report].
AB  - A 22 year-old female came to our clinic complaining of a swallowing disturbance
      and dyspnea. ENT examination revealed a spherical mass at the base of the tongue
      partially obstructing the airway. Scintigraphy with an iodine isotope confirmed
      that the mass was an ectopic thyroid. Under general anesthesia, and the mass was
      carefully dissected together with its the feeding vessels and transplanted into
      the right submandibular gland was removed the space that had been created. The
      postoperative course was uneventful. Thyroid function one month after surgery was
      at the same level as before surgery, and scintigraphy two months after the
      operation revealed normal uptake in the area of the transplanted thyroid.

PMID- 10897591
TI  - [Clinical study of 18 pediatric cadaveric renal transplantations: organ sharing
      in pediatric renal transplantation after enforcement of the organ transplant law
      in Japan].
AB  - Renal transplantation is considered to be the optimal replacement therapy for
      children with end-stage renal disease. However, the number of pediatric renal
      transplants in Japan is much lower than in the USA and/or Europe. Since October
      1997, pediatric(< 15 years) recipients are given priority over adult recipients
      for organ sharing, only if one or two HLA-DR antigen(s) are matched between the
      recipient and pediatric(< 15 years) donor. However, the number of pediatric
      transplants is not increasing. One hundred and twenty-four pediatric renal
      transplantations were performed in Tokyo Women's Medical University between 1983
      and 1999, of which 18(14.5%) were cadaveric transplants and the others (106,
      85.5%) were living-related transplants. We examined 18 pediatric cadaveric renal
      transplantations. Seven patients received their graft from pediatric donors less
      than 15 years of age and 11 from adult donors. The mean age at transplantation
      was 13.2 years (range 4.5-18.7 years). Major etiologies of renal disease are
      hereditary renal disease(38.8%), chronic glomerulonephritis(33.3%), and focal
      segmental glomerulosclerosis[FSGS] (16.7%). Zero matches in HLA-DR locus were
      observed in 72.2%. Patient survival rate was 100%. Graft survival rates at 1 and
      5 years after transplantation were 83% and 64% successively. There was no
      significant difference between the graft survival of cadaveric and living-related
      transplantation at 1 and 5 years. All 5 patients who received their graft between
      1994 and 1998 have maintained normal graft function. Causes of their graft loss
      were chronic rejection in 3, recurrence of FSGS in 2, primary non-function in 1,
      and graft thrombosis in 1. Donor age and HLA-DR mismatching did not affect the
      outcome. We propose that pediatric renal grafts should be provided to children
      with priority, regardless of their HLA-A, B and HLA-DR matching.

PMID- 10897592
TI  - [Clinical effects of trandolapril in chronic glomerulonephritis patients with
      renal insufficiency].
AB  - Trandolapril is a newly developed angiotensin converting enzyme inhibitor (ACEI)
      whose characteristic is that it undergoes hepatic excretion. ACEI appears to have
      a specific reno-protective and antiproteinuric role in patients with chronic
      glomerulonephritis(CGN). Although renally excreted ACEI tend to accumulate and
      cause side-effects in patients with renal dysfunction, the pharmacokinetics of
      trandolapril were not affected by renal dysfunction. We compared the effect of
      other renally excreted ACEI with those of trandolapril on serum creatinine (s
      Cr), creatinine clearance(Ccr), proteinuria and total protein(TP) in CGN patients
      who switched from another ACEI to trandolapril. Twelve hypertensive patients with
      chronic renal failure(nine males and three females, ranging from 30 to 72 years
      of age) who were treated by other renally excreted ACEIs for long periods(2 to 8
      years) with some effects on proteinuria and renal function, were enrolled in the
      present study. After ACEI therapy, s-Cr had decreased(2.09 to 1.80 mg/dl, p <
      0.01) as well as proteinuria(1.65 to 0.71 g/day, p < 0.01). A single daily oral
      dose of 1 mg of trandolapril was administered to these patients regardless of
      their blood pressure status and renal functions. After change to trandolapril
      therapy, s-Cr(2.25 to 2.06 mg/dl, p < 0.01) and urinary protein(1.82 to 1.34
      g/day, p < 0.05) significantly decreased. On the contrary, both Ccr and TP
      significantly increased at the level of 39.4 to 44.4 ml/min(p < 0.05) and 6.80 to
      7.02 g/dl (p < 0.01), respectively. No apparent side effects, such as
      hyperkalemia, hyponatremia, anemia or worsening of the existing renal dysfunction
      except for coughing, were observed in these patients. Furthermore, none of the 12
      patients treated with trandolapril required discontinuation of the compound. In
      conclusion, it was shown from this study that trandolapril is effective for the
      treatment of hypertensive patients with renal insufficiency irrespective of the
      original diseases. Thus, it can be envisaged that trandolapril is one of the most
      appropriate agents compared to other renally excreted ACEI for these patients
      with renal insufficiency. We recommend the change from other ACEIs to
      trandolapril, when renal dysfunction might be due to ACEI accumulation.

PMID- 10897593
TI  - [Contrast nephropathy with a non-ionic iodide medium in patients with normal and
      mildly impaired renal function].
AB  - Effects of infusion of a non-ionic contrast medium(iopamidol, 370 mg l/ml) on
      renal function in a normovolemic state were examined in patients with normal and
      mildly affected renal function who underwent coronary angiography(CAG). The
      patients were divided into three groups: group I (n = 69) with serum creatinine(S
      Cr) level < 1.0 mg/dl; group II (n = 50) with S-Cr level of 1.0 to 1.3 mg/dl and
      group III(n = 17) with S-Cr level of 1.3 to 2.0 mg/dl. Patients with S-Cr > or =
      2.0 mg/dl were subjected to 3-h hemodialysis immediately after CAG(group HD, n =
      11). Serum(S) and urine(U) values of Cr, Na, K, Cl, beta 2-microglobulin(beta
      2MG), and U-N-acetyl-beta-D-glucosaminidase(NAG) were measured before and 24 h
      after CAG. U-NAG and U-beta 2MG were corrected for U-Cr, and fractional excretion
      of beta 2MG(FE beta 2MG) was determined. Basal U-NAG/Cr, U-beta 2MG/Cr and FE
      beta 2MG were increased in groups III and HD, suggesting the preexistence of
      tubular dysfunction. S-Cr was increased significantly only in group I, but there
      was no change in S-beta 2MG. U-NAG/Cr after CAG was elevated in all the groups,
      whereas U-beta 2MG/Cr(or FE beta 2MG) was increased only in group III. Greater
      than two-fold increases of U-NAG/Cr were noted equally in groups I through III.
      In contrast, the greater than two-fold increase of U-beta 2MG/Cr(or FE beta 2MG)
      occurred more frequently in group III as compared to the other groups. The
      incidences of such cases in group HD were similar to those of group III. The half
      life of serum iodide concentration was significantly shortened by 3-h HD(1.8 +/-
      0.3 h vs. 15.9 +/- 3.8 h without HD). In conclusion, patients presenting S-Cr >
      or = 1.3 mg/dl were at high risk of renal tubular dysfunction even when contrast
      media was administered in the absence of significant increase in S-Cr. Whether an
      increase in U-NAG/Cr indicates tubular damage or is merely the result of tubular
      reabsorption of the agent remains to be clarified. Post-CAG hemodialysis
      efficiently eliminates contrast medium from the circulation.

PMID- 10897594
TI  - [Clinical evaluation of cases with massive ascites accumulation after
      discontinuation of CAPD: an attempt to establish the concept of the pre
      sclerosing encapsulating peritonitis(pre-SEP) state].
AB  - Sclerosing encapsulating peritonitis(SEP) is a most serious complication of
      continuous ambulatory peritoneal dialysis(CAPD). Although the criteria of
      diagnosis and guidelines for therapy of SEP have been proposed by the Japanese
      SEP Study Group already, SEP is refractory to treatment when the disease process
      is complete. It is important to detect the latent phase of SEP(pre-SEP state) in
      order to treat patients at an early stage. We evaluated the characteristics of
      ascites in four patients with massive ascites accumulation after discontinuation
      of CAPD. Age and the duration of CAPD of the subjects were 53.3 +/- 9.7 years and
      126.5 +/- 6.8 months, respectively. However, the patients were withdrawn from
      CAPD because of peritonitis or ultrafiltration failure. We also followed
      cytokines and parameters of collagen metabolism of ascites in two patients during
      adrenocorticosteroid therapy and conducted a histopathological evaluation of the
      peritoneum of an autopsy case who had died of pneumonia. Ascites seems to be
      exudative because of the high concentration of protein, cytokines and parameters
      of collagen metabolism such as interleukin-1 beta, interleukin-6, transforming
      growth factor-beta 1, procollagen 3 peptide, and type IV collagen 7S, the levels
      of which were 21.3 +/- 9.3 pg/ml, 8,153 +/- 7,327 pg/ml, 6.7 +/- 3.6 ng/ml, 89.3
      +/- 67.8 U/ml, and 59.0 +/- 36.2 ng/ml, respectively. The histopathological
      findings of the peritoneum from the autopsy case showed dense fibrous tissue
      permeated with inflammatory infiltration and widespread infiltration of fibrin.
      These findings suggested that the peritoneum was inflamed when massive ascites
      accumulated. The amount of ascites and concentration of cytokines and parameters
      of collagen metabolism of ascites diminished during adrenocorticosteroid therapy.
      We concluded that massive and refractory accumulation of ascites appearing after
      the discontinuation of CAPD should be regarded as a sign of the pre-SEP state,
      and prophylactic treatment should be started at this stage of disease.

PMID- 10897596
TI  - [Nephrolithiasis: a new approach to the old disease].
AB  - The epidemiology and metabolic causes of the nephrolithiasis may be different.
      The author discusses, in a very selective way, major advances in the
      understanding of this disease.

PMID- 10897595
TI  - [A case of hepatitis C virus-associated glomerulonephropathy presenting with MPO
      ANCA-positive rapidly progressive glomerulonephritis].
AB  - We report a case of hepatitis C virus-associated glomerulonephropathy presenting
      with MPO-ANCA-positive, rapidly progressive glomerulonephritis(RPGN). A 60-year
      old woman was admitted to our hospital for evaluation of RPGN. Laboratory
      evaluation revealed microhematuria, proteinuria(800 mg/day), anemia, renal
      failure(blood urea nitrogen 27 mg/dl, serum creatinine 2.2 mg/dl),
      cryoglobulinemia, hypocomplementemia, positive MPO-ANCA(232 EU), and hepatitis C
      virus infection(GOT 58 IU/l, GPT 38IU/l, HCV-RNA(PCR) 1,200 kcopy/ml, serotype
      1). After admission, the patient's renal function and anemia deteriorated
      rapidly, then prednisolone(30 mg/day) was started. After treatment her renal
      function gradually improved, then a renal and liver biopsy was performed. The
      renal biopsy revealed six sclerosing fibrous crescentic glomeruli in twelve
      glomeruli. Immunofluorescent examination revealed granular deposits of IgG, C3,
      and fibrinogen along the glomerular basement membrane and mesangial matrix. The
      pathogenesis of RPGN in this case may relate to the deposition of immune
      complexes in the glomeruli because immunofluorescent examination was revealed to
      be the immune-complex type, but not pauci immune type nephritis. Liver histology
      revealed chronic active hepatitis with mild piecemeal necrosis and did not reveal
      vasculitis. Although her renal function was improved after treatment with
      prednisolone, she suffered from pulmonary manifestations(dry cough etc.) on the
      120th hospital day. Suddenly she died because of pulmonary hemorrhage on the
      180th hospital day. These findings suggest that various HCV-induced immunological
      abnormalities, such as positive MPO-ANCA, cryoglobulinemia and
      hypocomplementemia, play an important role in the pathogenesis of this RPGN,
      although we could not demonstrate deposition within glomeruli of immune complexes
      containing HCV. The effect of interferon therapy on such immunological
      abnormalities remains to be documented. Since interferon is known to have
      immunomodulatory effects, we selected corticosteroid therapy. Future studies need
      to focus on the optimal treatment strategy for hepatitis C virus-associated
      glomerulonephritis.

PMID- 10897597
TI  - [The role of environmental factors in the formation of kidney calculi].
AB  - Various endo- and exogenous factors play a role in the urinary stones formation
      tract. The aim of the study was to define the type and frequency of
      hyperexcretion of lithogenic substances in school children population and to
      determine an influence of risk factors on hyperexcretion of crystallizing
      substances. The study included 220 school children. Preurolithiasis state (PS)
      was found in 30% children. The most frequently hyperoxaluria, hyperuricosuria and
      hypercalciuria were diagnosed and it may be connected with abnormal nutritional
      habits, excessive application of multivitamins, vitamin D and calcium,
      disturbances in drinking water chemical composition (higher amount of calcium,
      smaller amount of magnesium, abnormal pH). Urinary tract infections, particularly
      in children with obstructive uropathy are an important risk factor in the
      examined population. Positive familial history of urolithiasis in 43.3% children
      may indicate for the important role of the genetic factor in the pathogenesis of
      the disease.

PMID- 10897598
TI  - [Etiology of nephrolithiasis in children: own observation].
AB  - Recurrent formation of renal calculi may be prevented by selective medical
      therapy designed to correct underlying metabolic disturbances in urine
      biochemistry. The aim of the study was to estimate potential risk factors of
      urolithiasis in 102 children before ESWL treatment. Metabolic disturbances
      followed by anatomical malformations of urinary tract, recurrent urinary tract
      infections caused by urease-induced microorganisms are the most frequent risk
      factors. In single cases possible risk factors were: immobilization and chronic
      corticosteroid therapy.

PMID- 10897599
TI  - [Importance of dietary sodium in the hypercalciuria syndrome and
      nephrolithiasis].
AB  - The studies involved 20 children with idiopathic hypercalciuria (IH). An
      influence of urinary sodium excretion, and reflection of its intake, on urinary
      calcium excretion has been assessed. Children who were normocalciuric had
      significancy lower values of urine sodium excretion when compared with those with
      persisting hypercalciuria. The main factor responsible for hypercalciuria in
      children seemed to be urine sodium excretion. As urine sodium excretion reflects
      its intake, reduction dietary salt, rather than calcium intake, may be useful in
      the management of children with hypercalciuria and nephrolithiasis.

PMID- 10897600
TI  - [Uric acid metabolism in children with hyperuricosuria].
AB  - We treated 39 children with hyperuricosuria (18 boys and 21 girls aged between 6
      and 11 years). Treatment consisted of increased fluid intake, low salt and low
      purine diet and urine alkalization up to pH 6.5-6.8. We have selected two groups
      of patients with different uric acid [UA] metabolism parameters. In group I (21
      children) mean value of serum UA was 2.52 mg/dL, mean urine UA excretion was
      13.11 mg/kg/d and UA FE was 21.51%. In group II (18 children) mean value of serum
      UA was 4.7 mg/dL, mean urine UA excretion was 12.8 mg/kg/d and UA FE was 10.9%.
      In group I, treatment did not normalize uricosuria (13.57 mg/kg/d), urine pH was
      elevated (6.56). In group II uricosuria was diminished (8.37 mg/kg/d), urine pH
      was 6.37. 1. Disturbances of tubular secretion may be suspected in some children
      with hyperuricosuria and without hypouricemia. 2. The maintenance of urine pH
      within normal values is the basic of treatment in children with hyperuricosuria.
      3. In children suspected of tubular transport disturbances appropriate tests of
      uric acid metabolism should be performed.

PMID- 10897601
TI  - [Hyperuricosuria in children].
AB  - Hyperuricosuria (HU), defined as an increased urinary acid excretion, seems to be
      responsible for the of kidney stone formation. Hyperuricosuria was identified as
      a potential etiology of hematuria in children and adult patients too. The aim of
      the study was to analyze clinical course of hyperuricosuria in 77 children (43
      girls and 33 boys) treated in 1995-1999. We analyzed familial history of
      urolithiasis, reasons of hospital admissions, laboratory findings and treatment.
      HU has been suspected to cause hematuria in patients. Children with higher
      urinary acid excretion are in increased risk of stone formation.

PMID- 10897602
TI  - [Hypocitraturia in children with urolithiasis].
AB  - Inhibitors of crystallization process play an important role in renal-stone
      forming patients. One of well-known inhibitor is citrate. The aim of the study
      was to define the type of metabolic abnormality in children with nephrolithiasis
      and the role of urinary citrate excretion. 52 children with nephrolithiasis were
      examined. Hypocitraturia was observed in 42.3% of patients, most frequently in
      children with hypercalciuria, hyperoxaluria, and hyperoxaluria with
      hyperuricosuria. Low urinary citrate excretion found in patients with
      nephrolithiasis may play an important role in the pathogenesis of the disease.
      Urinary citrate excretion should be examined in patients with nephrolithiasis.

PMID- 10897603
TI  - [Urolithiasis and urinary tract abnormalities in children: own experience].
AB  - The study aimed analyzing case histories of 36 children (21 girls and 15 boys),
      from between 3 weeks and 17 years old, with urinary tract abnormalities, admitted
      to the Pediatric Nephrology Department for renal stone disease within a 5-year
      period (1995-1999). Most common clinical manifestations, requiring further
      urinary tract investigation, were: pain, urinary tract infections caused mainly
      by Gram-negative bacteria, and erythrocyturia. Most frequent anomalies observed
      in our patients were those resulting in urinary outlet obstruction. Disturbances
      in uremic acid and oxalate metabolism were abnormalities we have often found in
      the examined children. The majority of patients underwent a successful
      conservative treatment. The obtained results indicate that disorders in the urine
      flow are main risk factors for crystallization in children with urinary tract
      abnormalities.

PMID- 10897604
TI  - [Urolithiasis in children less than 4 years of age].
AB  - The aim of the study was to analyse the cases of nephrolithiasis in the youngest
      children from 2 months and 4 years. 30 children treated between 1955 and 1999
      were included in to the study. Nephrolithiasis causes, clinical course of the
      disease and risk factors for the urinary stone formation were taken under
      consideration.

PMID- 10897605
TI  - [Urolithiasis in children: an analysis of clinical cases].
AB  - The authors on the basing on clinical observation of 116 children with
      urolithiasis, in aged between 3 and 17 years have concluded the following: among
      the patients of the pediatric ward urolithiasis amounts to 9% of patients. It has
      been concluded that to diagnose urolithiasis ultrasounds are necessary, but in
      treatment and prevention an assay of crystallization components is indispensable.
      In all cases of children with urolithiasis, besides an infection, one must look
      for coexisting defects in the urinary tract.

PMID- 10897606
TI  - [A form of premorbid condition of urolithiasis and urinary stone composition in
      children with urolithiasis].
AB  - In diagnosis, monitoring and prophylaxis of urolithiasis it is important to use
      simple, non-invasive tests. The aim of the study was to define the value of
      crystallizing ratios in urine in correlation with chemical stone composition in
      presumptive diagnosis and monitoring patients with urolithiasis. The study
      involved 102 children. An analysis of chemical stone composition was carried out
      in 62 cases. A correlation between values of crystallizing ratios in the urine,
      indicating the kind of preurolithiasis state and chemical stone composition has
      been found.

PMID- 10897607
TI  - [Conservative treatment of urolithiasis in children].
AB  - Treatment of urolithiasis depends on the stone and secretion renal tubular
      transport disturbances. Conservative treatment of urolithiasis and prevention of
      stone formation in children should consist of: adequate fluid intake, low salt
      and animal protein diet in all stone formers; calcium-oxalate stones: diet
      containing a proper amount of dairy product, low oxalate diet, if indicated:
      thiazide diuretics, magnesium salts, citrate; uric acid stones: low purine diet,
      alkalization of urine up to pH 6.5-7.0, if indicated: allopurinol; infection
      stones: treatment of the urinary tract infection, low phosphate diet; cystinuria:
      low animal protein diet, alkalization of urine up to pH 7.0, if indicated:
      captopril, d-penicillamine.

PMID- 10897609
TI  - [New possibilities in cystine lithiasis therapy: preliminary report].

PMID- 10897608
TI  - [Results of ESWL treatment in children with urolithiasis: own experience].
AB  - Actually extracorporeal shock wave lithotripsy (ESWL) is the most frequent method
      in the treatment of urolithiasis in children. The aim of the study was to
      estimate the results of ESWL in children with urolithiasis. Between 1991 and 1999
      y, in our Department 260 "reno-ureteral units" in 203 children were treated by
      lithotripsy. Totally of 518 ESWL procedures were performed. In general efficacy
      of ESWL was 88.08%, in children with single stone in kidney--97.80%., with
      multiple stones in kidneys--78.65%, in ureterolithiasis--71.88%. For complete
      recovery in patients mean 1.99 ESWL procedures were performed on 1 "reno-ureteral
      unit" on the average diameter of the stone/stones 13.3 mm.

PMID- 10897610
TI  - [Metabolic disorders in children with urolithiasis].
AB  - Nephrolithiasis is a common disease of multifactorial ethiopatogenesis. The
      majority of stone formers has disturbances in the metabolism and excretion of
      stone constituents, promotors or inhibitors of crystallization. The aim of our
      study was to evaluate metabolic disturbances in children with nephrolithiasis in
      the early stages of the disease. Cases with severe urinary obstruction, infection
      and glomerular filtration decrease were excluded. Daily calcium, uric acid,
      oxalate, phosphate, sodium, potassium, chloride, citrate, and magnesium excretion
      was examined in 27 children (12 M, 15 F, mean age--10.4 +/- 3.9 y).
      Hypercalciuria (10 cases) and hiperurykosuria (8 cases) were most often found in
      the studied group. We concluded that early diagnosis of metabolic background of
      stone formation (promotors and inhibitors) enables to apply proper preventive
      measures.

PMID- 10897611
TI  - [Urinary calcium/creatinine excretion in children with isolated hematuria].
AB  - The aim of this study was to assess the oxalate excretion (Ox) in 23 children
      aged 3-17 years with haematuria (I), using the enzymatic method. Control group
      (II) consisted of 21 healthy children. The results showed out that in children
      with haematuria both mean oxalate excretion (Ox/ker) and mean calcium excretion
      (Ca) and calcium/creatinine ratio (Ca/ker) were higher than in control group.
      However, the differences were not significant important (p > 0.05). Significantly
      higher oxalate and calcium excretion was diagnosed in 5 children with renal stone
      disease and 8 children without stones but with paroxysmal abdominal pain and
      positive family history.

PMID- 10897612
TI  - [Urinary calcium/creatinine, phosphate/creatinine, magnesium/creatinine and
      Sulkowicz test in the second morning urine sample in neonates and infants].
AB  - The aim of the paper was to determine the values of the 5th and 95th percentiles
      of Ca/Cr, P/Cr and Mg/Cr, ratios in the second-morning urine samples in healthy
      neonates and infants. The collected Ca/Cr ratios were correlated with the results
      of Sulkowicz test performed on the same urine sample. The tests were done on the
      group of 30 neonates and 43 infants. The comparison of the 95th percentiles in
      the individual ratios in tested groups showed low values in the early newborn,
      distinctive increase in the first half followed by the decrease in the second
      half of the first year of live. There was no correlation found between the Ca/Cr
      ratios and the results of Sulkowicz tests.

PMID- 10897613
TI  - [Urolithiasis in children with cerebral palsy or following surgical treatment of
      myelomeningocele: preliminary report].
AB  - In 20 children with cerebral palsy and following treatment of myelomeningocele
      sonography of urinary tract was performed. In 7 out of them (3 with meningocele
      and 4 with cerebral palsy) calcified deposits in urinary tract have been found.

PMID- 10897614
TI  - [Changes of kidney parenchyma in children with nephrolithiasis after ESWL
      treatment in ultrasonography, power Doppler and thermovision monitoring].
AB  - The authors discuss the results ultrasonographic (USG), power Doppler (PD) and
      thermovision (TV) examination in monitoring changes of kidney parenchyma in 30
      children with nephrolithiasis after ESWL treatment. To monitor possible effect of
      shock wave on the kidney parenchyma the USG, PD and TV examination were done
      before ESWL treatment as well as, 48 hours and 3 months following the treatment.
      Parts of kidney parenchyma localized on the way of shock wave to the stone were
      analysed. Echogenicity of kidney parenchyma was analysed by comparison of echo
      amplitude in subsequent USG examinations. Parenchymal blood flow by computer
      analyse was estimated. In TV examination the temperature distribution in the
      place of skin kidney projection was estimated. Changes in echogenicity of kidney
      parenchyma and impaired kidney parenchymal blood flow 48 hours after ESWL were
      found. In TV examination 48 hours after ESWL transient reduction in skin
      temperature was observed in the place of shock wave transmission. In 3 months
      after ESWL disturbances in the kidney parenchyma in USG, PD and TV were not
      observed.

PMID- 10897615
TI  - [Results of the treatment of pre-urolithiasis state in children with recurrent
      urinary tract infections].
AB  - Urolithiasis often coexists with recurrent urinary tract infections (RUTI). The
      aim of the study was to determine the correlation of preurolithiasis state (PS)
      and recurrent urinary tract infections and to establish an effect of the
      treatment UTI recurrence incidence. PS was found in 202(21.1%) children, most
      frequently: hyperoxaluria--in 61/202 (30.2%), hypercalciuria--in 32/202 (15.8%),
      and hyperuricosuria--in 30/202 (14.9%) children. Complex metabolic abnormality
      was observed in 62/202 (30.7%) patients. Therapeutic management comprised of:
      antibacterial prophylaxis, high fluid intake, proper diet, correction of urine
      pH, and pharmacological treatment if necessary. Disappearance of RUTI and PS in
      88/202 (43.6%) children, disappearance of RUTI in spite of persistent PS in
      36/202 (17.8%), and decrease of RUTI in 54/202 (26.7%) patients were method. In
      110/202 (54.5) children PS disappeared.

PMID- 10897616
TI  - [Health status and physical development of children delivered by mothers who
      suffered from nephrotic syndrome in their infancy].
AB  - Numerous complications of nephrotic syndrome due to either the illness itself or
      repeated courses of high-dose corticosteroids have been well recognised for
      several score years. However, investigations concerning children of ex-patients
      are lacking. The purpose of this study was to assess physical development and
      health state in the group of children whose mothers had suffered from the
      idiopathic nephrotic syndrome during their childhood. 34 such children were
      studied. Thorough medical history was taken from children and their mothers and
      available medical documents data were obtained. Physical examination was
      performed and centile position of weight, height and their proportion was stated.
      The authors found that stillborn foetus, premature or low birth weight newborn
      incidence is much higher than in general population and the percentage of
      overweight and obesity is higher in the studied group than in general population.
      To confirm these findings further investigations with greater number of patients
      are necessary.

PMID- 10897617
TI  - [CD3-CD25 lymphocyte population and blood serum Il-2R in children with
      liponephrosis].
AB  - It has been suggested that the immune system is involved in the development of
      lipoid nephrosis. The aim of the study was to estimate whether an elevated serum
      concentration of soluble interleukin-2 receptor (sIL-2R) is caused by increased
      expression of IL-2 receptors on the surface of lymphocytes T (CD3+CD25+). 20
      children with lipoid nephrosis and 15 healthy children served as control were
      evaluated. T cell subpopulations were assayed with flow cytometry, using
      monoclonal antibodies. The concentration of sIL-2R was determined by enzyme
      linked immunosorbent assay (ELISA). The patients with lipoid nephrosis had
      elevated serum levels of sIL-2R compared with healthy controls. Although the
      subpopulation of T cell CD3+CD25+ was decreased in nephrotic children. These
      results could testify against direct contribution of T cell immune response in
      the pathogenesis of lipoid nephrosis.

PMID- 10897618
TI  - [Total antioxidant status (TAS) in children with nephrotic syndrome].
AB  - The aim of the study was to estimate total antioxidant status (TAS) as the most
      reliable factor involved in antioxidant protection in children with nephrotic
      syndrome. 28 children with NS (12 with first episode and 16 with relapse NS) aged
      4-16 were included into the study. TAS was estimated using two-regent Randox
      Total Antioxidant Status test in plasma. Laboratory investigations were performed
      before steroid treatment. RESULTS: 1) in children with NS TAS was significantly
      reduced comparing to controls (0.81 +/- 0.14; 1.21 +/- 0.62 mmol/L; p = 0.002),
      2) negative correlation between Tchol and LDL and TAS was found (TAS vs Tchol p =
      0.0005, R = 0.61; TAS vs LDL p = 0.03, R = 0.41), 3) TAS was higher in children
      with the first episode of NS comparing to children with following relapse (0.88
      +/- 0.07; 0.75 +/- 0.16; mmol/l; p = 0.14). CONCLUSION: In children with NS
      reduced antioxidant protection is one of the factors leading to renal injury and
      may be a consequence a cause reason of lipids abnormalities.

PMID- 10897619
TI  - [Resistance to therapy in primary nephrotic syndrome: effect of MDR1 gene
      activity].
AB  - MDR1 gene encodes for a transmembranous glycoprotein, gp-170, which acts as a
      drug export pump and is also a cyclosporine(CsA)-binding protein. This study
      aimed at evaluating MDR1 expression in NS sensitive(S) and resistant(R) to
      therapy (steroids/S/, cyclophosphamide/C/, CsA) patients. Twenty six boys, 13
      girls aged 3-8 years were included to the study. MDR1 was analysed using: 1)
      evaluation of gp-170 activity according to DiC2/3/ [3,3-Diethyloxa-carbocyanine
      Iodide] by means of flow cytometry and as 2) mRNA expression of MDR1 determined
      by RT-PCR. The analysis was performed in the lymphocyte subset CD4/CD45RA
      presenting suppressor-inducer activity. Negative control, Jurkat-T-cell line, not
      expressing the MDR1 phenotype, was transfected with viral expression vector
      containing a full-length cDNA for the human MDR1 gene. We found that: in SR-NS
      the high expression of MDR1 was associated mainly with the suppressor-inducer T
      cells (CD45RA+CD4+) and was subsequently enhanced during an ineffective treatment
      with C and/or CsA. C-R-NS and CsA-R-NS were partially reversible by S- and R
      Verapamil; this was in vitro confirmed by inhibition of export pump activity, gp
      170. SS-NS, C-S-NS and CsA-S-NS presented the low expression and activity of MDR1
      comparing to R-children (p < 0.001) and healthy controls (p < 0.00001).
      Resistance to therapy in NS patients seems to be resulted from the enhanced
      expression of MDR1 gene and subsequent high activity of export pump P-gp-170.
      Calcium channel blockers may reverse the MRD1-related resistance in the therapy
      of NS. Analysis of MDR1 may help to detect of suspected therapy resistance in NS.

PMID- 10897620
TI  - [Does the changed Th1/Th2 activity in children with the assessment of body water
      in children with nephrotic syndrome: initial results].
AB  - T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of
      the study was to determine whether the activity of T-helper-1 (Th1) and T-helper
      2 (Th2) cells are predictive for steroid sensitivity in children with primary NS.
      These parameters were assessed at the onset of disease, before initiation of
      steroid therapy. Two groups of NS children were retrospectively formed according
      to steroid sensitivity(SS) or resistance(SR). Activity of Th1 and Th2 cells was
      defined by the production of IL-2, IFN-gamma and IL-4, IL-10 (ELISA),
      respectively, in the supernatants of the culture of CD4+ T cell cultures
      activated with autologous monocytes presenting tetanus toxoid (TT). Peripheral
      lymphocyte subsets were determined using double or triple colour flow cytometry.
      In SS children with NS we found the cytokine synthesis indicating the
      predominance of Th2 activity. We conclude that prior to treatment the Th1 and Th2
      cell activity provides a useful tool to evaluate the probability of steroid
      sensitivity in patients with primary NS.

PMID- 10897621
TI  - [Value of bioelectrical impedance analysis in the assessment of body water in
      children with nephrotic syndrome: initial results].
AB  - The study aims at assessing the value of bioelectrical impedance analysis in
      estimation of fluid compartments in children with nephrotic syndrome. The study
      included 23 children aged, 2 and 20.5 y. In 9 children in remission measured
      parametres were normal. In the group of 14 children with relapses and oedemas,
      significantly higher TBW and ECM/BCM were observed. These parameters decreased
      during the course of disease with clinical improvement, but did not reach normal
      levels at the disappearance of oedemas. BIA is a simple, non-invasive and
      valuable method for assessment of total body water and fluid compartments.

PMID- 10897622
TI  - [Activation of coagulation cascade in children during an idiopathic nephrotic
      syndrome relapse].
AB  - The objective of this study was to assess concentrations of selected markers of
      coagulation in children with relapse of idiopathic nephrotic syndrome during a 6
      week therapy. Study groups: 22 subjects (32 relapses)--14 males, 8 females (mean
      age 7.15 +/- 1.5 y.) with no thrombotic complications were included into the
      study. All children were clinically steroid-sensitive. METHODS: Coagulation
      markers (platelet count, thrombin time, APTT, INR, fibrinogen 1 + 2 fragments (F1
      + 2), thrombin-antithrombin complexes (TAT), serum levels of D-dimer (DD), fibrin
      monomers (FM) and antithrombin activity (ATIII)) were measured three times: on
      admission, after 2 and 6 weeks. The control group consisted of 13 healthy
      children. RESULTS: Serum concentration of TAT or F1 + 2 did not differ between 3
      stages (p > 0.05). However, values at 0 and 2 weeks were significantly higher
      than in control group (p < 0.05). We found no correlation between TAT or F1 + 2
      and FBG, ALB, TCH, TG levels. [table: see text] CONCLUSIONS: The coagulation
      cascade in relapse of NS was activated during first 6 weeks of therapy whereas
      metabolic disturbances (low ALB, high FGB, TCH, TG, high platelets) normalized.
      It is speculative whether it was caused by active immunological process but
      definitely it resulted in "prothrombotic state" in INS patients.

PMID- 10897623
TI  - [Bone mineralization and calcium/phosphate metabolism in children with nephrotic
      syndrome].
AB  - The study was carried out in 20 children aged 6-18 years receiving long-term
      corticosteroid treatment for nephrotic syndrome. In these children densitometric
      evaluation of bone by DEXA method (total body and spine) and ultrasound
      measurement of heel were performed. Moreover, basic parameters of calcium
      phosphate metabolism were determined. Osteoporosis and osteopenia were diagnosed
      in 6/20 (30%) patients. Disturbances of bone mineralisation were accompanied by
      hyperhydroxyprolinuria, hypercalciuria, hypocalcemia and also by some clinical
      symptoms. The results of these pilot investigations point at necessity periodical
      assessment of bone mineralisation and calcium-phosphate metabolism in children
      with nephrotic syndrome receiving corticosteroid treatment.

PMID- 10897624
TI  - [The assessment of Helicobacter pylori eradication with the urea breathing test
      (13C UBT)].
AB  - The purpose of the study was to assess the efficacy of Helicobacter pylori (HP)
      infection treatment in children with the nephrotic syndrome, using non-invasive
      urea breathing test (13C UBT). The study comprised 20 children with nephrotic
      syndrome treated with prednisone. Children were divided into two groups: those
      who recurred prednisone for a short time (1-3 months) and those treated longer
      than 6 months. In all children gastroscopic examination, histopathologic
      assessment of gastric mucous membrane specimens and 13C UBT were performed. 65%
      of nephrotic children was HP (+). In those treated for 1-3 months incidence of HP
      infection was 40%, whereas in those were treated longer than 6 months it was 90%.
      In all children treatment of HP infection was instituted. Seven weeks after
      cessation of treatment its efficacy was assessed by 13C UBT. The treatment was
      successful in all nephrotic children. In the nephrotic controls with negative
      histopathologic assessment for HP infection the results of UBT were normal.
      CONCLUSION: 1. Children with the nephrotic syndrome are more susceptible to HP
      infection as compared with healthy ones. 2. In those children treatment of HP
      infection is efficient. 3. 13C UBT allows to estimate HP infection treatment
      efficacy in a non-invasive way.

PMID- 10897625
TI  - [Results of treatment of lupus nephritis in children. Own experience].
AB  - The study aims at assessing the results of treating lupus nephritis in 31
      children, aged 4-16 years at the diagnosis of the disease. Renal biopsy was
      performed in 29 patients. Patients were divided into 2 groups. Group 1 included
      15 children treated in 1980-92 and group 2 included 16 children treated in 1993
      98. The average age, sex and follow-up were similar in both groups. All children
      were treated with corticosteroids. Alkylating agents were administered to 12
      patients in group 1 and in 14 in group 2. Group 2 patients were given
      cyclophosphamide in monthly intravenous pulses, and methylprednisolone according
      to the Mendoza regime. In Group 1, 8 remissions (53%) were observed. Better
      results with more aggressive treatment were obtained in group 2--13 remissions
      (81%).

PMID- 10897626
TI  - [Changing clinical course of hemolytic uremic syndrome in children].
AB  - An incidence of hemolytic-uraemic syndrome as a cause of the acute renal failure
      in childhood, its early survival rate and long-term sequela quences were compared
      in the 1970s, 1980s, and 1990s in the same geographical area. 196 children with
      HUS were treated between 1972-1999. 94% had a typical D+ HUS. The majority were
      of patients severely ill with 87% requiring peritoneal dialysis of an average 14
      days duration. The children were grouped into three 9-year periods for comparison
      (1972-1980, 1981-1989, 1990-1999). 105 patients were followed for 2-27 years
      (mean 1 years). An incidence of HUS as a cause of ARF in childhood ranged from
      58% and 50% in the 1970s and 1980s to 30% in the past decade. With time survival
      rate has improved dramatically over the years from 80% and 75% to 97% in the
      1990s. Deo spite better short term outcome the late consequences of HUS are
      serious. The longer the follow-up, the greater percentage of patients with severe
      outcome. At last follow-up only 32% children showed full recovery. 33% are on
      renal replacement therapy or have impaired renal function. The severity of the
      initial lesions to the kidney measured by the duration of anuria is a marker of
      poor late prognosis. With improving early outcome the clinical significance of
      HUS is focusing on its severe long-term consequences.

PMID- 10897627
TI  - [The I/D polymorphism of the ACE gene in children with Henoch-Schoenlein
      purpura].
AB  - The study group consisted of 24 children with Henoch-Schoenlein purpura (HSP) (13
      girls and 11 boys, aged 66-233 months) who were treated in the Ist Pediatric
      Department between 1980 and 1998. The I/D polymorphism of ACE gene was determined
      by PCR amplification of genomic DNA with primers flanking the polymorphic region.
      Our preliminary results suggest lack of association between ACE genotype and
      kidney function. However, further follow-up studies based on sufficient number of
      participants are necessary to elucidate the role of ACE polymorphism in
      appearance and progression of renal symptoms in HSP.

PMID- 10897628
TI  - [Urine culture analysis in children with urinary tract infections treated at
      Pediatric Clinical Department in Bytom in the years 1998-1999].
AB  - Sensitivity of bacterial strains causing urinary tract infections was analysed.
      High sensitivity of bacteria to nitrofurantoin, guinolones and cephalosporines-
      mainly of the III generation, as well as minute sensitivity to penicillins were
      demonstrated.

PMID- 10897629
TI  - [Beta-2 microglobulinuria in children with vesico-ureteral reflux and recurrent
      urinary tract infections].
AB  - Recurrent urinary tract infections in children with vesico-ureteral reflux are
      the one of risk factors in the process of reflux nephropathy. One of markers of
      early kidney parenchyma damage is beta 2-microglobulin. The aim of the study was
      to evaluate the value of beta 2-microglobulin excretion in urine and its serum
      levels in children with vesico-ureteral reflux and recurrent urinary tract
      infections. It was found that abnormal urinary excretion of beta 2-microglobulin
      and its serum levels of proceeded post-inflammatory changes in kidney parenchyma
      observed in imaging examinations of urinary tract and impared parameters of renal
      function in biochemical analyses.

PMID- 10897630
TI  - [Clinical assessment of Uro-Vaxom in the treatment and prophylaxis of recurrent
      urinary tract infection in children: preliminary results].
AB  - The aim of the study was to determine the efficiency of Uro-Vaxom in the
      treatment of recurrent urinary tract infection in children. We examined 19 girls
      in aged 4-17 years treated in our Department since Jan 1998 until Jan 1999 for of
      recurrent urinary tract infection induced by E. coli (RUTI). All girls have been
      cured with Uro-Vaxom in single daily dose for 3 months. Disappearance of RUTI in
      47% of children and decrease in RUTI in 42% reveals that Uro-Vaxom plays
      significant role in the treatment of this disease.

PMID- 10897631
TI  - [Specificity of uroflowmetry as a screening test for the urinary tract diseases
      in children].
AB  - The aim of the study was to determine the specificity of uroflowmetry a screening
      testing the urinary diseases in children. We have investigated 70 children.
      Patients were divided in 3 groups. Group I included 38 children with recurrent
      urinary tract infections, group II included 18 children with enuresis, and group
      III included 14 children with preurolithiasis state. Pathological uroflowmetry
      was detected in 11 children (15.7%), which indicating the need of using this test
      during diagnostic process.

PMID- 10897632
TI  - [Simple renal cysts in children: treatment with ethyl alcohol injection into
      their lumen].
AB  - OBJECTIVE: The authors assess the efficacy of treatment of simple renal cysts
      with 95.5% ethyl alcohol injected into their lumen. MATERIAL AND METHOD: The
      diagnosis was confirmed by traditional US and color Doppler, urography, and renal
      scintigraphy. In four children with simple renal cysts ultrasound-guided
      puncture, aspiration of fluid and instillation of 95.5% of ethyl alcohol for 15
      20 minutes were performed and a needle was withdrawn. RESULTS: In three children
      3 weeks after the procedure diameter of cysts began to diminish and by the 5th
      week cysts were not detected in US. In the fourth child the cyst started to
      diminish 2 months after the procedure and disappeared after the next 3 months.
      There was no cyst recurrence after the procedure (average follow-up: 22 months).
      CONCLUSIONS: In 4 children treatment of simple renal cyst with 95.5% ethyl
      alcohol has proved safe and effective treatment.

PMID- 10897633
TI  - [Ultrasound-guided renal biopsy with automatic needle with a leader].
AB  - The aim of this work was to discuss the results of percutaneous renal biopsy
      under control of ultrasound, using automated needle. 110 specimen in 55 children
      aged 3-18 years were obtained. Adequate biopsy was obtained in 53 children. Only
      in 26% of children the number of glomeruli in each specimen was below 8. The most
      frequent complication was microscopic haematuria, lasted 1-3 days, which was
      shown in 70.9% of children. Perirenal haematoma smaller than 2 cm was observed in
      about 12% of children and pain during the first day after biopsy in 20% of
      examined children. CONCLUSION: Percutaneous renal biopsy using automated biopsy
      needle under control of ultrasound is safe and efficient method, which is used
      for definitive diagnosis.

PMID- 10897634
TI  - [Renoscintigraphy applied with etylenedicysteine labeled with technetium 99m and
      SPECT technique as a method of examining kidneys in children with vesicoureteric
      reflux].
AB  - Vesicoureteric reflux (VUR) can lead to renal parenchymal damage. Renal scarring
      is an important cause of chronic renal failure and hypertension in children. The
      significance of possible effects determines the necessity of early diagnosis of
      urinary tract pathology. The aim of the paper was to evaluate the morphology and
      function of kidneys with VUR using selected radioisotope techniques, and to
      compare the sensitivity of planar technique and single-photon emission computed
      tomography (SPECT) technique in detection of renal scarring. In 45 children with
      VUR the following test were performed: ultrasonography, renoscintigraphy with
      technetium-99m-ethylenedicysteine (EC-Tc-99m) and technetium-99m
      dimercaptosuccinic acid (DMSA-Tc-99m) scintigraphy with planar and SPECT mode.
      Stage of VUR correlates with stage of cortical lesions estimated as a value of
      effective renal plasma flow (ERPF) in kidney, as well as scarring intensity in
      static scintigraphy. The use of SPECT increases sensitivity of examination for
      detection small, single scars. It seems that SPECT should be used more frequently
      in children in the group of scarring risk. That would allow for earlier diagnosis
      of renal scarring, enabling efficient treatment. Due to the correlation between
      ERPF and parameters obtained in DMSA scintigraphy, renoscintigraphy with EC-Tc
      99m may be applied to monitor the progress of renal scarring.

PMID- 10897635
TI  - [Dual X-ray absorptiometry (DEXA) in children with chronic diseases].
AB  - Dual energy X-ray absorptiometry (DEXA) can be used for the measurement of bone
      density at the level of lumbar spine, whole body scan, and also for the
      measurement of bone mass content (BMC), lean body mass (LBM), and fat body mass
      (FBM). Although this method has been originally developed for the diagnosis and
      monitoring of osteoporosis in adults, it is used in children with chronic
      diseases like chronic renal failure, chronic gastrointestinal and rheumatological
      diseases. However, children with chronic disease often demonstrate statural
      growth disturbances and decreased growth velocity. Therefore, their actual height
      does not correspond to the actual chronological age. Normal values of DEXA for a
      given age are based on data from children with normal height. Interpretation of
      DEXA regardless of the actual height, which is usually stunted, may lead to false
      conclusions and wrong therapeutic attitudes. Thus, when interpreting results
      obtained in such patients a few transformations and calculations should be done.

PMID- 10897636
TI  - [Epidemiology and clinical course of HCV infection in children and adolescents
      with chronic renal failure].
AB  - The aim of the study was to evaluate epidemiology and clinical course of HCV
      infection in children and adolescents with end-stage renal disease. The study
      involved 70 patients, aged 1-25 years, 31 M, 39 F: group of 40 dialysed (27 HD,
      13 CAPD) and 30 patients suffering from different chronic renal disease as a
      control group. Anti-HCV antibodies were assayed by EIA 3rd gene (Abbott
      Diagnostic) and were sought by LIATEK HCV 3rd gene. HCv RNA was detected and
      measured by a standardised HCV RNA PCR assay (Amplicor Roche). HCV genotypes were
      identified by InnoLIPA (Innogenetics). HCV infection was diagnosed in 20 (50%)
      dialysed and in 3 (10%) non-dialysed patients. None of the HCV infected patients
      presented the clinical symptoms of hepatitis; the mild activity of ALT was
      observed in 8 cases only. HCV viremia was relatively low: 365 x 103 copies/mL in
      PD and 110,9 x 103 copies/mL in HD patients. 3 genotypes of HCV were identified:
      1a, 1b and 4c/4d. In 3 cases liver biopsy was performed, no cirrhosis was
      diagnosed.

PMID- 10897637
TI  - [Cyclic vomiting with ketosis as a cause of acute kidney dysfunction: own
      clinical experience].
AB  - The aim of the study was to evaluate renal activity during cyclic vomiting with
      ketosis. The clinical material was obtained from 50 cases of children
      hospitalized in Department of Pediatrics Military Medical University within 1993
      1999 what makes about 1% of all patients. The examined group consisted of 26 boys
      (52%) and 24 girls (48%). Three of the children were repeatedly hospitalized (3
      to 8 times) because of acetonemic vomiting. The special attention during the
      laboratory studies was paid to evaluation of renal activity. Vomiting with
      ketosis were associated with temporary kidneys acute dysfunction in 46% of cases.
      In 98% of cases the parenteral hydration was necessary. Ketonemic vomiting with
      kidneys dysfunction was observed mainly with the children in pre-school age.

PMID- 10897638
TI  - [Renal transplantation in children in the Czech Republic].
AB  - The aim of the study is to review results of pediatric renal transplantation in
      center in Prague, Czech Republic. Results are compared with the registry data
      from Europe and United States. Patients, who underwent RTx at the University
      Hospital Motol, Prague (Czech Republic) between 1977 and the end of 1999, were
      analyzed. Since 1977 128 Rtx from cadaveric donors were performed in children in
      mean age 12.8 +/- 4.1 years. In 1977-1987, patients were treated with prednisone
      and azathioprine, and since 1988, cyclosporine A, added to prednisone and
      azathioprine. Sequential quadruple immunosuppression was used only in few highly
      sensitized patients. Acute graft rejections were treated with methylprednisolone
      pulses, antithymocyte globulin and monoclonal antibodies OKT3, in selected cases.
      In 1988 and 1999 cyclosporine A was replaced by tacrolimus as initial
      immunosuppression in some patients. The number of Tx ranged between 5 and 13 per
      year. Patients and graft survival were significantly lower in the first time
      period 1977-1987 with a median patients 5-year survival rate of only 50% and
      graft survival 30%. In the last period (1988-1999) 5-year patients survival is
      90% and 5-year graft survival is 68% (p = 0.01). Two cases of posttransplant
      lymphoproliferative disease were diagnosed so far. One of them died several
      months after RTx, the other received cytostatic therapy for Hodgkin tumor and
      graft function was maintained. Main causes of graft failure were chronic
      rejection followed by acute steroid resistant rejections, severe cytomegalovirus
      infections, noncompliance, vascular thrombosis, and recurrence of original
      disease.

PMID- 10897639
TI  - [Hypertension in children with chronic renal failure].
AB  - Hypertension is one of the main risk factors of mortality for children on renal
      replacement therapy. It has also been recognised as one of the major risk factors
      for progression of renal failure. The aim of the study was to define the
      prevalence of hypertension in children with chronic renal failure, treated in a
      single centre, and to assess the efficacy of its diagnosis and management.
      Hypertension was present in 27% of 40 children before the onset of chronic renal
      failure, increasing to 57% with the development of CRF, and reaching 86% at onset
      of dialysis. Reflux nephropathy, hemolytic-uraemic syndrome and glomerular
      disease were most frequently associated with severe hypertension. ACE inhibitors
      (70%), diuretics (52%), and calcium channel blockers were the most frequently
      used antihypertensives with 49% of the children being on monotherapy. Despite
      therapy 43% of children had elevated blood pressure levels and 16% had
      echocardiographic signs of LVH. A 24 hour ambulatory blood pressure measurements
      were more sensitive in diagnosing hypertension and assessing adequacy of blood
      pressure control. Early and intensified treatment should prevent end organ damage
      though optimal blood pressure values to aim obtain are still to be defined.

PMID- 10897640
TI  - [Bone mineral density in children with end-stage renal disease].
AB  - The aim of the study was to evaluate bone mineralisation in comparison to
      chronological age, bone age and high age in children with end-stage renal
      disease. Fourty-four patients (16 female, 28 male) aged 7-16 years were examined.
      DXA bone densitometry of total body, bone age evaluated by Greulich-Pyle method
      and high age were performed in all patients. In our patients bone, and high age
      were significantly decreased in comparison to chronological age. In contrast mean
      value of Z-score TG BMD bone and high age compared to mean value of Z-score TB
      BMD for chronological age were increased significantly. We conclude that bone
      mineralisation should be compared with or high age not to chronological age in
      patients with end-stage renal disease.

PMID- 10897641
TI  - [Risk factors of adynamic bone disease in children with end-stage renal failure:
      personal experience].
AB  - The aim of the study was to estimate predisposing factors which can cause
      adynamic bone disease (ABD) and biochemical markers, bone densitometry results,
      bone histomorphometry in 17 children with this from of the renal osteodystrophy.
      Half of these of patients were treated with alphacalcidol pulses. In 47% of
      patients hypercalcemic episodes were noted, 76% had PTH level < 50 pg/ml. Four
      patients with osteoporosis (low bone volume at histological analysis) were
      distinguished. Two of them were treated with corticosteroids, 1 was immobilized
      for a long time.

PMID- 10897643
TI  - [Effect of lipid lowering diet on serum lipids in peritoneal dialysis patients].
AB  - The aim of the study was to assess an effect of lipid lowering diet on serum
      lipids in peritoneal dialysis patients. Total cholesterol (TC) decreased after 3
      months of low-fat diet from 203.7 mg/dl to 181 mg/dl, probably due to increased
      P/S ratio (PUFA/SFA) from 0.4 to 0.57. After another 3 months of the diet, a
      decrease in P/S ratio and concomitant increase in TC and LDL-C levels were found.
      Nutritional status of patients during lipid lowering diet was stable.

PMID- 10897642
TI  - [Bone metabolism markers and bone histomorphometry in children with chronic renal
      failure in predialysis period during growth hormone treatment].
AB  - The aim of the study was to estimate biochemical bone metabolism markers and bone
      histomorphometric parameters in children with chronic renal failure (CRF) treated
      with recombinant human growth hormone (rhGH). Twelve children with CRF aged 2
      13.4 years were treated with rhGH 1-1.1 IU/kg per week and alfacalcidol. Bone
      biopsies were performed before and after 12 months of therapy. An increase in the
      biochemical markers of bone formation and bone resorption were noted. A
      statistically significant increase in mineral apposition rate (MAR) was observed
      in bone histomorphometry. The administration of active vitamin D metabolites
      enable proper bone mineralization in fast growing children with CRF during rhGH
      treatment.

PMID- 10897644
TI  - [Sulphur amino acids, vitamin B12 and folic acid in children with chronic renal
      failure].
AB  - Aim of the study was to: 1) estimate plasma profile of sulphur AA in children
      with chronic renal failure (CRF) and in children on hemodialysis (HD), and 2) to
      evaluate any correlation with serum folic acid (FA) and vitamin B12. PATIENTS: 32
      pts with CRF: 9 with GFR > 20 ml/min/1.73 m2 (group 1), 9 with GFR < 20
      ml/min/1.73 m2 (group 2), and 14 pts on HD (group 3). METHODS: plasma
      homocysteine (Hcys), methionine (Met), cysteine (Cys), serine (Ser) were measured
      with gas chromatography. Serum FA and vit. B12 were measured using MEIA method.
      RESULTS: median Hcys concentrations were the lowest in group 1: 5 mumol/l vs 9
      mumol/l (group 2) and 20 mumol/l (group 3) (p = 0.03). Similarly, the lowest Met
      levels were observed in group 1--26 mumol/l, vs 66 mumol/l (group 2) and 281
      mumol/l (group 3) (p = 0.001). Median Cys level in group 1 was 98 mumol/l vs 54
      mumol/l (group 2), and 122 mumol/l (group 3) (p = 0.02). No differences were
      found in median Ser levels: 153 mumol/l (group 1) vs 239 mumol/l (group 2) and
      240 mumol/l (group 3). The median concentrations of FA were 6.3 ng/ml (group 1)
      vs 8 ng/ml (group 2) and 15 ng/ml (group 3) (NS). Median concentrations of vit.
      B12 were 256 pg/ml (group 1) vs 379 pg/ml (group 2) and 322 pg/ml (group 3) (NS).
      There were no correlation between sulphur AA and FA and vit. B12 levels. The only
      difference between pts with Hcys levels remaining in lower and upper quartile
      concerned Met concentration (38 vs 263 mumol/l, p < 0.02) and GFR (p < 0.01).
      CONCLUSIONS: Hyperhomocysteinemia develops already in moderate CRF. In pts on HD
      levels of Met and Cys are also raised. FA and vit. B12 concentrations are normal
      and do not correlate with plasma concentrations of sulphur AA.

PMID- 10897645
TI  - [Blood serum hepatocyte growth factor in children with chronic renal failure
      treated with CAPD and HD].
AB  - HGF--hepatocyte growth factor--belongs to the growth factors family, derivatives
      of plasminogen. HGF is a potent mitogen for hepatocytes, and has also renotropic
      properties. The study aimed at analysing HGF serum concentration in 20 children
      on continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis (HD)
      treatment. 10 healthy children served as a control group (K). CAPD group has been
      examined during routine monthly control, whereas HD group before a haemodialysis
      session. In HD treated children the highest HGF concentration was obtained in
      comparison to children on CAPD and control group. There was no significant
      difference HGF levels between children on HD and healthy ones. We found no
      relationship between the dialysis treatment duration, mean arterial pressure
      values, serum total cholesterol, triglycerides, ionised calcium concentration,
      haemoglobin concentration, hematocrit and serum HGF concentration. In examined
      group of children with chronic renal failure the highest HGF values were noted in
      children on HD, not strictly observing the dietetic regime and proper daily fluid
      intake. Diminished HGF concentration in children on CAPD could be explained by
      the absence of stimulating action of heparin and by transperitoneal removal of
      substances false by elevating HGF. It is necessary to carry out studies in larger
      group of children with chronic renal failure on CAPD in order to estimate
      transperitoneal clearance of HGF and its metabolites.

PMID- 10897646
TI  - [Prevalence of Helicobacter pylori-specific IGG and IGA in children and
      adolescents with chronic renal failure].
AB  - Helicobacter pylori, a bacteria first described in 1984, since that time is
      linked with chronic gastritis and duodenitis. Dyspeptic symptoms and chronic
      gastritis are common in patients with chronic renal failure (CRF). The aim of the
      study was to evaluate of Helicobacter pylori-specific IgG and IgA prevalence in
      73 CRF children and possible link of H. pylori infection and dyspeptic symptoms.
      Anti-H. pylori IgG antibodies were present in 20.5% CRF children (treated
      conservatively--21%; on CAPD--9%; chronically hemodialysed--29.6%), IgA
      antibodies was present only in 3 dialysed children (4.1%). Comparing to adult CRF
      patient, a lower rate of H. pylori infection was observed. No correlation between
      H. pylori seropositivity and a presence of dyspeptic symptoms was observed.
      Prevalence of H. pylori antibodies was higher in older CRF children and
      adolescents.

PMID- 10897647
TI  - [An incidence and etiology of Tenckhoff catheter in patients treated with CAPD].
AB  - Continuous ambulatory peritoneal dialysis (CAPD) is a renal replacement therapy
      of choice in small children, the elderly, diabetics, subjects with cardiovascular
      disease and with difficulties in vascular access. Frequent complication of this
      method is the infection of the Tenckhoff catheter exit site, definition of which
      has not been firmly established yet. The aim of this study was to assess the
      frequency of catheter exit infections, its bacterial etiology and the efficacy of
      antibiotic treatment. The study material consisted of 21 subjects (11 female, 10
      male) treated with CAPD in 1992-99 at our department, mean age 19.8 +/- 11.8 yrs,
      with mean CAPD treatment time 33 +/- 27 months. They were divided into two
      groups: group I--patients aged > or = 5 yrs, and group II--patients aged 15 yrs.
      Mean catheter usage time was 15.8 +/- 14.9 months. 43 cases of catheter exit site
      infection was diagnosed (0.7 case of infection per patient per year). Infection
      frequency was found to be 1 case in 9.4 months and 1 in 26.5 months, in group I
      and II, respectively (p < 0.001). Catheter usage in two groups was 10.4 +/- 8.2
      and 21.4 +/- 15.4 months, respectively (p < 0.01). The most frequent pathogen was
      S. aureus (31 cases), with 5 cases of MRSA strains found. Antibiotic treatment
      was applied according to Keane's recommendations and it lasted 13.2% of CAPD
      treatment duration. In conclusion, catheter exit site infection occurred more
      often in children under the age of 5 yrs, and the catheter usage time was
      significantly shorter in this group of patients.

PMID- 10897648
TI  - [CAPD treatment in children with renal amyloidosis].
AB  - The aim of the study was to summarize the experience in the treatment of chronic
      renal failure due to secondary amyloidosis in the course of juvenile rheumatoid
      arthritis. Fourteen children aged 7.5-17.7 years were treated with dialysis; 12
      with CAPD, 2 with HD. Our results indicate that CAPD is a proper dialysis
      technique for children with amyloidosis, despite a high rate of complications in
      early period of CAPD, such as: bleeding, leaks, hernias, and impaired wound
      healing.

PMID- 10897649
TI  - [A role of hemodialysis in the treatment of acute renal failure in children less
      than 5 years of age].
AB  - Mortality in acute renal failure (ARF) still exceeds 50%. However, while the
      outcome data for ARF in adults are readily available, similar data for pediatric
      population are scarce. Children survival rate varies between centres,
      particularly in regard to age and size of a child, and cause of ARF. Dialysis
      continues to be a major supportive intervention in severe acute renal failure.
      There are few data available that address treatment modality impact on ARF
      outcome. The youngest patients are usually treated with peritoneal dialysis,
      though sometimes hemodialysis is used even in children with very low birth body
      weight. We reviewed a 9-year experience with hemodialysis in children under 5
      years of age. 33 children (13 boys, 10 girls) were treated with hemodialysis in
      the analysed period. Their mean age was 26.8 +/- 23.0 years, mean body weight
      10.6 +/- 4.6 kg. Cardiac surgery and haemolytic-uremic syndrome were the major
      causes of ARF in the studied group. Dialysis duration, ultrafiltration rate,
      maximum blood flow, mortality and its risk factors were analysed. 232 dialyses
      were conducted in the studied group, mean 6 dialyses per patient. Mean dialysis
      time was 85 +/- 42 min for the first and 135 +/- 38 min for consecutive
      procedures. Urea reduction rates in the first and following dialyses were 50% and
      58% respectively. Maximum blood flow was 7.4 ml/kg/min, i.e. higher than
      recommended. However, no adverse events were caused by that. Mortality rate was
      38%. Hemodialysis may be used in small children, when indicated, with no higher
      death rate than standard peritoneal dialysis.

PMID- 10897650
TI  - [Quality of life in children and adolescent with end-stage renal disease treated
      with dialysis and kidney transplantation].
AB  - This study investigates the quality of life of 139 patients remaining on
      alternative therapies for end-stage renal disease. Data from self-report
      questionnaires concerning physical activity, physical and social well-being,
      signs of depression and general assessment of situation, and "hope for future"
      were compared. Results indicate that self-assessment of quality of life (physical
      activity, physical and social well-being) among transplant patients is the best
      compared to both dialysis groups. These differences sustained in spite of
      deterioration of general health state with time. There were no differences
      between dialysis groups in terms of evaluated parameters. Overall results of
      quality of life assessment expressed by patients treated with hemodialysis seem
      to slightly improve during treatment.

PMID- 10897651
TI  - [Factors influencing the development of chronic renal allograft nephropathy in
      children].
AB  - Chronic renal graft nephropathy (CRGN), with progressive deterioration of graft
      function and development of chronic graft pathology remains the main cause of
      late graft loss. Overall 191 patients, at aged 1.5 to 19 years were evaluated,
      divided in two groups: #1 (n = 103) with pathomorphological CRGN pattern in renal
      biopsy, and #2 (n = 88) with no chronic changes (22) or no indication to biopsy
      (66). Several factors were evaluated, including HLA matching, PRA, early graft
      function, early and late acute rejection, hypertension index, proteinuria,
      hemoglobin and albumin level, CsA dosing, blood levels and instability, CMV
      infection, CMV in-situ presence in the graft and correlations with graft survival
      and time post-transplant when CRGN assessed with Banff and CADI scales, occurred
      in renal biopsy, were analyzed. Statistical analysis showed, that significantly
      lower CsA blood level and dosage at 1,2,3 years post-transplant, CsA blood level
      instability, acute rejection within first year post-transplant, poor control of
      hypertension, proteinuria, lower hemoglobin level and hypoalbuminemia were major,
      while delayed graft function, CMV infection and CMV in-situ presence in renal
      tissue were minor factors affecting development of CRGN.

PMID- 10897652
TI  - [Critical evaluation of preparing pediatric recipients for renal transplantation:
      central waiting list analysis].
AB  - Transplantation is optimal modality of the renal replacement therapy (RRT),
      particularly in children. The number of transplants and improvement of tissue
      typing may depend not only on overall number of procured organs, but also on the
      number of properly prepared recipients. The cases of pediatric recipients on
      central waiting list were analyzed. From 117 cases placed on the list (which is
      only about a half of the whole dialyzed population), 25% were temporarily
      disqualified and in 30% the period of time from introducing RRT to referral the
      data and blood to transplant center was about one year. In 45% of disqualified
      patients the reason was uncorrected urological defect or missing current medical
      data from dialysis centers. This condition seems to be unacceptable and requires
      many efforts to improve.

PMID- 10897653
TI  - [Analysis of causes of death in children and adolescents on chronic peritoneal
      dialysis and hemodialysis in 10 year period: single center experience].
AB  - Causes of death in children and adolescents treated with chronic peritoneal
      dialysis or hemodialysis in 1990-1999 in single centre were analysed. Overall 131
      patients were treated, including 55 on peritoneal dialysis (PD) and 76 on
      hemodialysis (HD). Overall mortality in a 10-year period was 12% (16 patients).
      10 patients in PD (18%) and 6 patients in HD group (7.8%) died. The main causes
      of death in PD patients were cardiac insufficiency, sudden cardiac arrest,
      ischemic stroke and atherothrombotic disease. In HD patients the main cause of
      death was hemorrhagic stroke.

PMID- 10897654
TI  - [Bilateral renal obstruction caused by cystine stones in a child with Henoch
      Schonlein syndrome].
AB  - Haematuria is a typical symptom of glomerular involvement in Henoch-Schoenlein
      syndrome in children. The authors present an unusual case of haematuria and
      deterioration of renal function caused by cystine stones in a child with
      anaphylactic purpura. This 6 year old girl was hospitalized because of severe
      gastrointestinal symptoms in the course of a typical Henoch-Schoenlein syndrome.
      After 4 weeks of illness--the child demonstrated haematuria and oliguria with
      severe loin pain and a rise in serum creatinine to 5.8 mg%. Urine findings of
      mainly non-glomerular erythrocytes and slight proteinuria were suggestive of a
      non-glomerular cause of renal failure. Ultrasound examination revealed the
      unexpected finding of bilateral kidney obstruction caused by multiple renal
      stones. Cystine crystals observed under microscopic examination of the urinary
      sediment and a positive cyanide-nitroprusside test suggested cystinuria as the
      cause of nephrolithiasis. High water intake and alkalization of urine and
      captopril for cystine excretion reduction resulted in fast improvement of renal
      function and and with time complete dissolution of calculi. The symptoms of
      Henoch-Schoenlein syndrome resolved over several weeks, and the child did not
      develop any signs of glomerular involvement.

PMID- 10897655
TI  - [Generalized tuberculosis as a cause of renal amyloidosis in a 9-year- old girl].
AB  - We present a case of a 9 years old girl with generalized tuberculosis diagnosed
      at the age of 5. Renal amyloidosis was diagnosed 21 months later. Clinically
      amyloidosis has been presented with steroid-resistant nephrotic syndrome, which
      within 15 months led to end stage renal failure. The girl is on automatic
      peritoneal dialysis with no signs of active tuberculosis up to now.

PMID- 10897656
TI  - [Familial, recurring plasma infusion dependent thrombotic thrombocytopenic
      purpura/hemolytic uremic syndrome].
AB  - Two siblings with chronic relapsing TTP/HUS from early childhood are presented.
      An onset of the disease was probably neonatal period and it did not involved the
      organ until puberty. During puberty the course of the disease aggravated with
      renal involvement and became fulminant in a girl who died disseminated TTP. Her
      older brother had episode of severe atypical HUS responding to plasma therapy.
      Now, his renal function is normal but the symptoms are depend an regular,
      prophylactic plasma infusions.

PMID- 10897658
TI  - [Multiorgan dysfunction syndrome complicating hyperosmolar hyperglycemic syndrome
      as the primary feature of juvenile diabetes].
AB  - Diabetic ketotic acidosis and hyperosmolar hyperglycemic syndrome are regarded as
      the most serious diabetes complications. Acute renal failure frequently develops
      simultaneously with the symptoms of multiorgan disfunction and might be a factor
      indicating the severity of the primary disease. Authors present a case of a 11
      year-old boy with acute renal failure due to defective perfusion and disseminated
      intravascular coagulation as the complications of hyperosmolar hyperglycemic
      syndrome. This syndrome was the first feature of juvenile diabetes. Intensive
      treatment of fluid and electrolyte disorders, mechanic ventilation, renal
      replacement therapy, and close collaboration of trained nephrologist with
      intensive care unit specialists allowed to cure critical health states and
      improve the course of diabetes.

PMID- 10897657
TI  - [Index of histopathological changes in rapidly progressive glomerulonephritis: a
      preliminary report].
AB  - We present the case of an 8-year-old girl with rapidly progressive
      glomerulonephritis. The activity and chronicity index of histopathological
      changes in this patient was determined in 2 renal biopsies performed in a 25
      month interval. The determination of this index in renal biopsies may be useful
      in the choice of glomerulonephritis with bad prognosis therapy.

PMID- 10897659
TI  - [Different effect of angiotensin convertase inhibitors and AT1 receptor blockers
      on renal function in patients with chronic renal failure: report of two cases].
AB  - In two patients with chronic renal failure (CRF) different effects of angiotensin
      convertase inhibitors (ACEI) and angiotensin receptor 1 blockers (AT1B) were
      observed. In patient 1 with CRF due to hemolytic-uremic syndrome (HUS), with
      arterial hypertension (HT) and proteinuria, a switch from AT1B to ACEI led to
      significant deterioration of renal function. After restitution of AT1B, renal
      function returned to previous range. The 2nd patient with CRF and severe HT,
      without proteinuria, due to atypical HUS, was on CAPD. Because of severe HT he
      received 3-4 hypertensives and ACEI in full dose was the main medication. Despite
      relatively low urea and creatinine values while on dialysis and high residual
      diuresis several attempts an end of CAPD was unsuccessful because of hyperkalemia
      and unacceptable increase of urea and creatinine concentrations after few days.
      Conversion from ACEI to AT1B enabled withholding CAPD, stabilisation of renal
      function and good control of HT. It seems that in patients with CRF without
      hyperfiltration syndrome and sensitive to changes in glomerular hemodynamics, in
      whom blockade of angiotensin action is needed AT1B may be a better option than
      ACEI. When using ACEI in patients with CRF, it is important to adjust the dose to
      renal function.

PMID- 10897660
TI  - [Ultrasound of exit-site and tunnel infections in children on peritoneal
      dialysis].
AB  - Ultrasound diagnosis of catheter related infections in patients on peritoneal
      dialysis is easy to perform diagnostic procedure which enables more precise
      diagnosis and better follow-up of therapy. The authors present three cases of
      exit site and tunnel infections in children, illustrating the value of ultrasound
      evaluation in their diagnosis and in decisions on conservative treatment or
      catheter removal.

PMID- 10897661
TI  - [Secondary hyperparathyroidism as a cause of delayed functioning of renal graft.
      Reports of two cases].
AB  - Parathormone (PTH) exerts vasomodulatory effect. In patients with severe
      hyperparathyroidism (HPTx) post transplant (Tx) PTH level decreases slowly and
      this could be a reason of delayed graft function. Case 1: 19 years old female; 2
      years of CAPD-renal Tx lost after 8 years--6 years on hemodialysis (HD), clinical
      symptoms of severe HPTx (iPTH > 1300 pg/ml). Elective parathyroidectomy was
      cancelled as patient received the second graft. Then she was oliguric and
      required regular HD from the 4th day after Tx. We observed increasing resistance
      index (RI) and finally no diastolic blood flow in graft USG-Doppler scan. Ten
      days after Tx, the patient was revised surgically and renal biopsy was performed.
      No pathology but slight ATN was found. At the same time iPTH level was 1225
      pg/ml. Plasmapheresis (PF) was introduced, decreasing iPTH level to 850 pg/ml,
      995 pg/ml, and 345 pg/ml respectively. After the second PF urine output increased
      (to 600 ml). Serum creatinine level decreased from 7.3 to 1.3 mg/dL within the
      next 10 days. Actually (5 months post Tx) graft function remains stable
      (creatinine 1.2 mg/dl). The level of iPTH at the second month after Tx was 756
      pg/ml, at 4th month--439 pg/ml. Case 2: M.P. 20 years old female initially on HD,
      then Tx, lost after 5 months because of FSGS recurrence--again HD therapy. She
      developed severe secondary HPTx (iPTH level > 1300 pg/ml). Planned
      parathyroidectomy was cancelled as she received a second transplant. After Tx she
      was anuric for 5 weeks and was treated with HD. She had high RI index in repeated
      USG-Doppler scans, blood flow in renal cortex was deceleration. Repeated renal
      biopsy showed no pathology and PF therapy was introduced. After the first PF the
      patient started to urinate, after the 5th--the urine output was 1000 ml. Overall
      10 PFs were done. Now, 13 months after Tx, graft function is satisfactory
      (creatinine level 2.1 mg/dL). The level of iPTH in 4th month after Tx was 772
      pg/ml, in 10th month--631 pg/ml. We suggest that disturbances in graft blood flow
      were influenced by high level of iPTH, decreased successfuly by PF therapy.

PMID- 10897662
TI  - [Mechanism of progression of chronic renal failure and new treatment strategies].
AB  - Chronic renal failure is a self-perpetuating, progressive disease leading to end
      stage renal failure, even if primary insult to the kidneys was removed.
      Progressive course of disease is caused by chronic interstitial inflammation
      leading to fibrosis, tubular atrophy, and glomerular sclerosis. Main predictive
      risk factors of the disease progression include: proteinuria, systemic and
      glomerular hypertension. It is presumed that in most cases progressive course of
      the disease is related to genetic predisposition to greater activity of renin
      angiotensin system. Among attempts to slow progressive course of the disease
      effective are interventions acting on renin-angiotensin system, endothelin 1 and
      on profibrotic cytokines. Role of dietary factors and potential treatment
      modalities are discussed.

PMID- 10897663
TI  - [Hepatitis C virus infection in renal diseases: state of knowledge, therapeutic
      problems and perspectives].
AB  - Chronic infection with hepatitis C virus (HCV) is estimated to affect almost 170
      million individuals worldwide. 20-30% of these individuals develop cirrhosis and
      its sequelae. Only 15-20% of patients with chronic hepatitis C achieve a
      sustained virological response to interferon monotherapy. The prevalence of anti
      HCV antibodies in dialysis patients varies between 1% and 29% in Western Europe.
      In patients with ESRD on maintenance HD therapy, in whom a blunted immune
      response per se is observed, the usefulness of IFN-alpha therapy is usually
      discussed in the context of subsequent transplantation associated with intensive
      immunosuppressive treatment regimens. A recent study has shown that in this
      patient group renal transplantation is associated with a fivefold increase in
      posttransplantation liver disease as well as a relative risk of death of 3.3
      compared to HCV-negative patients. Thus, eradication of HCV infection in patients
      with ESRD may substantially reduce morbidity and mortality in renal allograft
      recipients. The imbalance of T-helper (Th) lymphocyte cytokine production may
      play an important role in the immunopathogenesis of chronic HCV infection. Little
      is known about the effects of IFN-alpha therapy on Th1/Th2 activity in HD
      patients. The type of immune response against infectious agents is determined in
      part by the pattern of cytokines secreted by T lymphocytes. Th1 cells promote
      cellular immunity against infectious agents, while Th2 cells induce humoral
      immune response and immune tolerance activity. The measurement of Th1/Th2 profile
      should increase our understanding of the immune status of patients with HCV
      infection. Therefore, the recently presented studies were undertaken to evaluate
      the influence of IFN-a therapy on Th1/Th2 balance in HD patients with chronic HCV
      infection.

PMID- 10897664
TI  - [VEGF is an essential molecule for glomerular endothelial cells and its excretion
      in urine might be a unique marker of glomerular injury].
AB  - A glomerulus is a functional unit of the kidney, and endothelial cells in the
      glomerulus are often exposed to more than 5 times higher pressure than peripheral
      capillaries. Glomerular development proceeds through angiogenesis and VEGF was
      shown to mediate the angiogenesis. VEGF is constitutively expressed in the
      glomerulus from the embryo to adults. When VEGF signal was blocked by the
      antibody, glomerular endothelial cells were swollen and capillary lumen was
      interrupted. Changes were more prominent in the juxta-medullary than in the
      cortical glomerulus. A major VEGF receptor, Flk-1/KDR, is specifically localized
      to the glomerular endothelial cell among tissues and more predominantly in the
      juxta-medullary than in the cortical glomerulus. As capillary pressure is higher
      in the juxta-medullary than in the cortical glomeruli, endothelial cells in the
      former are exposed to more tension than those in the latter. VEGF might be a
      protective molecule for endothelial cells against tension. The effect of VEGF on
      the repair of an impaired glomerulus was evaluated in the rat Thy-1
      glomerulonephritis. VEGF inhibited early endothelial injury and accelerated
      consequent remodeling of the glomerulus. In the patient study, VEGF excretion in
      the urine was independent from its serum or plasma level, but increased as renal
      function decreased. VEGF signaling is essential in glomerular development,
      maintenance and repair. VEGF excreted in the urine might reflect its generation
      in the kidney and be a unique marker of renal function.

PMID- 10897665
TI  - [Molecular dynamics of proteins found exclusively in glomerular epithelial
      cells].
AB  - The visceral glomerular epithelial cells or podocytes of the renal glomerulus are
      uniquely characterized by a large cell body and numerous foot processes. These
      foot processes are kept wide open to facilitate passage of glomerular filtrate
      and are held together tenuous slit diaphragms that bridge the filtration slits.
      By contrast, nephrosis results in the apical displacement of the glomerular
      filtration slit membrane by newly formed intercellular occluding-type junctions.
      It is still unknown what kind of proteins are involved in the morphological
      changes of podocytes in nephrotic conditions. Our data show that one isoform of
      ZO-1 found exclusively in the tight junction(TJ) is expressed in the highly
      specialized slit diaphragm. In nephrotic rats induced by puromycin
      aminonucleoside(PAN) treatment or perfusion with polycations such as protamine
      sulfate(PS), the slit diaphragms are displaced by occluding-type junctions. In
      these cases, ZO-1 was concentrated along both the newly formed occluding-type
      junctions and the remaining slit diaphragms. Also, perfusion of glomeruli with
      polycations induces tyrosine phosphorylation of some proteins including ZO-1
      within 15 min. What kind of molecules contribute to such a signal transduction? A
      possible candidate is podocalyxin, which is the major sialoglycoprotein of the
      rat glomerular epithelial cell. We cloned rat podocalyxin gene and analyzed its
      molecular nature. Furthermore, we have made a number of monoclonal antibodies
      against rat podocytes. Monoclonal antibody P-31 we made recognizes a novel
      intermediate filament-associated protein(p250) in rat podocytes. Our data suggest
      that p250 would play a important role in the organization of the intermediate
      filament network in both normal and diseased conditions.

PMID- 10897666
TI  - [Analysis of urinary mononuclear cells as markers of renal injury].
AB  - The presence of macrophages(M phi) in the urine of patients with
      glomerulonephritis(GN) reflects the pathological events in the kidney, and we
      have discovered the following correlations between the M phi phenotype and the
      pattern of renal injury. 1) Urinary macrophage(M phi) counts increase in patients
      with proliferative GN, especially in the presence of active glomerular
      lesions(glomerular tuft necrosis, crescent, and endocapillary proliferation). In
      patients with hematuria, a combination of urinary M phi and T-lymphocyte counts
      can be used to differentiate proliferative GN from non-proliferative renal
      disease(hereditary nephropathy and idiopathic renal hematuria). 2) The urinary M
      phi of patients with active proliferative GN express Fc gamma RIII(CD16)
      regardless of the type of GN. 3) There are two types of urinary CD68+ cells,
      CD68+25F9- cells(infiltrating M phi) and CD68+25F9+ cells(mature M phi). The
      CD68+25F9- cell counts in the urine correlate well with the activity of
      proliferative GN, and the CD68+25F9+ cell counts in the urine correlate with the
      magnitude of non-selective proteinuria and with the subsequent decline of renal
      function. The CD68+25F9+ cell count increase in the urine of patients with focal
      segmental glomerular sclerosis, but their numbers are negligible in minimal
      change nephrotic syndrome. These findings indicate that analysis of the urinary M
      phi phenotype is a useful strategy for evaluating renal injury as a "risk-free
      renal biopsy".

PMID- 10897667
TI  - [Surgical stress and CARS: involvement of T cell loss due to apoptosis].
AB  - The term compensatory anti-inflammatory response syndrome(CARS) is the cytokine
      antagonist cascade which down-regulates the inflammatory cascade that appeared to
      contribute to the onset of bacterial infection. CARS represents
      immunosuppression, in which state reduced numbers of T cells in blood were
      encountered. Here we have determined whether this T cell loss is a consequence of
      bacterial antigen-mediated activation-induced cell death(AICD). By flowcytometric
      analysis, less than 0.3% of freshly isolated T cells from healthy volunteers and
      patients with severe pneumonia were identified as apoptosis. However, during
      culture, the rate of apoptosis in peripheral blood T cells from patients was 3.0
      + 0.9%, and increased further in the presence of anti-CD3(7.4 + 2.1%) and
      decreased when IL-2 was added(4.4 + 1.3%). In contrast, there were no changes
      observed in healthy volunteers on addition of anti-CD3. Further, anti-CD3
      significantly increased susceptibility to apoptosis of CD45RO+ T cells, but not
      CD45RA+ T cells from patients. Collectively, these findings demonstrated that
      bacteria-reactive T cells were more susceptible to AICD, and AICD of CD45RO+ T
      cells, therefore, provides an explanation for the loss of bacteria-reactive T
      cells during CARS.

PMID- 10897668
TI  - [SIRS and the coagulation of normality].
AB  - Systemic inflammatory response syndrome(SIRS) is a pathologic condition
      associated with infection and tissue injury and it frequently leads to multiple
      organ dysfunction syndrome and disseminated intravascular coagulation(DIC).
      Pathologic events observed in SIRS can be attributable to the actions of
      cytokines such as tumor necrosis factor-alpha(TNF-alpha) and interleukin-1 beta.
      These cytokines activate monocytes and endothelial cells to induce the expression
      of tissue factor on their cell surfaces. Tissue factor then activates the
      extrinsic pathway of the coagulation system to induce microthrombus formation.
      These cytokines also contribute to microthrombus formation by decreasing the
      endothelial expression of thrombomodulin and glycosaminoglycans that regulate the
      coagulation system. Consequently, these cytokines induce DIC. These cytokines can
      activate neutrophils to release various inflammatory mediators which are capable
      of damaging the endothelial cell. The resultant endothelial cell injury, together
      with the microthrombus formation, may lead to microcirculatory disturbance which
      plays a role in ischemic organ dysfunction. Although physiological anticoagulants
      such as antithrombin and activated protein C can prevent endothelial cell injury
      by inhibiting leukocyte activation, heparin does not. Thus, these anticoagulants
      except for heparin may be effective in treating DIC associated with SIRS.

PMID- 10897669
TI  - [Modulation of SIRS].
AB  - SIRS is a systemic inflammatory reaction occurring in the course of several
      diseases and it is considered that SIRS is hyper-cytokinemia. Recently, the
      control mechanism of IL-10 anti-inflammatory cytokine for the superfluous
      inflammatory reaction by inflammatory cytokines such as TNF has received
      considerable attention. IL-10 tends to inhibit monocytes/macrophages and the
      production of TNF, IL-1 and IL-8 is suppressed. In addition, the production of
      oxygen radicals and proteases from activated neutrophils is directly suppressed.
      IL-10 seems to control the generation of tissue injury that accompanies
      neutrophil activation by also suppressing CD11a, CD11b and TNF receptor
      expression of neutrophil surface directory. In this study, we observed the effect
      of a drug that controls cytokine production by lymphocytes after LPS loading,
      using an antibacterial agent and steroids, to observe the effect of the drug on
      the control mechanism of SIRS. As the result, TNF production by lymphocytes was
      suppressed by macrolide, new quinolone and fosphomycin. Steroid also dosage
      dependently suppressed TNF production of lymphocytes after 24 hours of incubation
      while IL-10 production increased. From these results, it was considered that some
      antibacterial agents and steroids have anti-inflammatory or a modulating effect
      on inflammation. Clinically, the control of inflammation in patients with SIRS by
      these drugs is expected.

PMID- 10897670
TI  - [SIRS in surgical stress].
AB  - It has been suggested that SIRS are triggered by superfluous pro-inflammatory
      cytokine production, and that organ injury is caused by uncontrolled inflammatory
      responses. However, the results of clinical studies, on the usefulness of
      specific cytokine antagonists and anti-TNF antibodies for the treatment of septic
      shock, have been unsatisfactory. The reason for this might have been that when
      uncontrolled inflammatory reactions progressed locally, anti-inflammatory
      reactions were elevated in the circulated blood by way of CARS, thus the timing
      of administration and pharmacokinetics did not match clinical course. Recent
      research has shown that SIRS is always accompanied by CARS, and since it seems to
      do the amplitude of SIRS and CARS to each other so that there may be a deep
      valley, if there is a high mountain. We introduce the recent knowledge which
      indicates that SIRS is a preliminary alert for not only organ dysfunction but
      also immunosuppression after severe injury or major surgery.

PMID- 10897672
TI  - [Feasibility of a simple measurement for white blood cell by immunologically
      measured granulocyte elastase in whole blood].
AB  - Using whole blood sample, we examined the correlation between concentration of
      granulocyte elastase (GEL) in granulocyte obtained by immunoassay and white blood
      cell counts. The correlation between concentration of GEL and granulocyte cell
      counts was also examined. The correlation coefficient between concentration of
      GEL and white blood cell counts was R = 0.87, and that between concentration of
      GEL and granulocyte cell counts was R = 0.91. The correlation coefficients of
      outpatients and patients with diseases accompanied by inflammation except for
      tumors were better than those of inpatients. The GEL concentration in granulocyte
      using whole blood sample well responded to the white blood cell counts against
      the tolerance for a short time, such as after operations. Especially on screening
      tests of diseases accompanied by inflammation and primary care, analysis of GEL
      in whole blood is not only useful for observation of inflammation and its
      progress but also suggests possibility of converting GEL to white blood cell
      counts or granulocyte. Furthermore, because it can be measured by easy-operative
      latex agglutination turbidimetric method, an easy measurement system can be
      built. Extended usage of the system as a rapid diagnostic tool on emergency tests
      in general clinics and hospitals are expected.

PMID- 10897671
TI  - [SIRS and CARS: discussion based on the pathologic condition of acute
      pancreatitis].
AB  - Relationship between SIRS and CARS in the pathologic condition of acute
      pancreatitis was discussed. SIRS promotes excessive inflammatory reaction and
      CARS induces the susceptibility to infection. Both conditions can develop into
      organ failure in acute pancreatitis. Hence, countermeasures for both conditions
      are mandatory in the care of patients with acute pancreatitis.

PMID- 10897673
TI  - [Evaluation of F1 + 2/TAT ratios in Japanese patients with antiphospholipid
      syndrome].
AB  - The clinical manifestations of the antiphospholipid syndrome(APS) include
      arterial and venous thrombosis and a fetal loss, but the pathogenic mechanisms
      remain unclear. To clarify the mechanism of thrombogenic state in APS, we
      investigated the markers for thrombosis including thrombin-antithrombin
      complex(TAT) in patients with antiphospholipid antibodies(aPL). Prothrombin
      fragment 1 + 2(F1 + 2) in patients with APS and in autoimmune disease patients
      with aPL increased significantly compared with those obtained in autoimmune
      disease patients without aPL or in control subjects. However, there was not a
      significant difference in the TAT level of each group, suggesting that the
      formation of TAT was impeded in APS. To investigate which aPL is responsible for
      the disturbance of the TAT formation, the ratio of F1 + 2/TAT was calculated. The
      ratio increased in patients with lupus anticoagulant, especially with prolonged
      kaolin clotting time, and furthermore the ratio strongly increased in patients
      with IgG type-anticardiolipin antibodies(aCL). Our results suggest that IgG-aCL
      is associated with thrombogenic state in APS because free thrombin is present in
      patients' blood by impeding the formation of TAT by mainly IgG-aCL.

PMID- 10897674
TI  - [Characteristics of plasma DNA and its application for detection of K-ras gene
      mutation].
AB  - DNA diagnosis is useful and significant for clinical oncology, but its use is
      limited due to a difficulty in preparing tumor-derived DNA materials. To overcome
      this problem, we investigated the characterization of plasma DNA and it
      application to successfully detecting K-ras mutation at codon 12 in normal
      persons, hematopoietic neoplasms, and solid tumors. The range of plasma DNA in
      each group was 15.8 +/- 5.2 ng/ml, 43.3 +/- 29.8 ng/ml, and 26.8 +/- 17.0 ng/ml,
      respectively. The ranges in patients with solid tumor were gradually decreased to
      the normal level of around 15 ng/ml in 3 weeks postoperatively. Plasma DNAs
      consisted of about 200 bp DNA fragmentation and were convenient for PCR
      amplification of K-ras gene. The mutation at codon 12 by PCR-RFLP analysis was
      detected in 13(27%) of 49 patients with solid tumors such as pancreatic cancer,
      breast cancer, colon cancer, and gastric cancer. The diagnostic specificity was
      100%. Serial observations by the PCR-RFLP analysis revealed disappearance of the
      mutant K-ras about 7 days after successful curative surgery in a patient with
      gastric cancer.

PMID- 10897675
TI  - [The clinical study on KL-6 and SP-D in sera of patients with various pulmonary
      diseases].
AB  - It has been reported that serum levels of KL-6 and surfactant protein D(SP-D) can
      be useful indicators for interstitial pneumonia(IP). In the present study, we
      evaluated the clinical significance of KL-6 and SP-D by measuring the serum
      levels of patients with various pulmonary diseases by enzyme-linked immunosorbent
      assay. Serum levels of KL-6 in patients with idiopathic interstitial
      pneumonia(IIP), collagen disease with interstitial pneumonia(CDIP), lung
      cancer(LC) and LC with idiopathic interstitial pneumonia were significantly
      higher than of those in healthy controls. Moreover, serum levels of KL-6 were
      significantly higher in patients with active IP than in those with inactive IP.
      Serum levels of SP-D in patients with IIP and CDIP were significantly higher than
      of those in healthy controls. When a cut-off level of KL-6 or SP-D in sera was
      defined as a value of healthy controls representing the means + 2SD, the serum KL
      6 positive diagnostic rate for IP(79.2%) was higher than that of SP-D(66.7%). The
      SP-D positive diagnostic rate for lung diseases other than IP(11.6%) was lower
      than that of KL-6(34.9%). The serum concentration of KL-6 in patients with the
      pulmonary diseases significantly correlated with that of SP-D. These findings
      suggest that KL-6 may be superior in the sensitivity of IP and can be used to
      evaluate the disease activity of IP. In addition, SP-D may be more specific for
      IP than KL-6.

PMID- 10897676
TI  - [A case of ANCA positive idiopathic crescentic glomerulonephritis initiated with
      fever and liver dysfunction].
AB  - We studied a case of a 63 year old Japanese man who presented in October, 1994
      with general fatigue, low grade fever, micro hematuria and leukocytosis, elevated
      CRP as well as liver dysfunction. A liver biopsy at that time revealed mild
      cholangiolitis. Six months later he was admitted because of weight loss, protein
      urea, and renal failure. At that time he was positive for antineutrophil
      cytoplasmic antibody(ANCA) with perinuclear staining patter(p-ANCA) done by
      indirect immunofluorescence. He was also positive for anti-myeloperoxidase
      antibody(MPO-ANCA) done by ELISA. A renal biopsy showed idiopathic crescentic
      glomerulonephritis with pauci-immune type(ICGN). Despite therapy with steroids
      and cyclophosphamide, which improved his subjective symptoms, his renal failure
      accelerated necessitating hemodialysis which he has been on for over four years.
      In conclusion, this patient has a rare case of ICGN that presented with liver
      dysfunction similar to autoimmune hepatitis. Since ANCA has been known to be
      associated with systemic vasculitides as well as chronic inflammatory
      diseases(e.g. ICGN, microscopic polyarteritis nodosa, ulcerative colitis or
      autoimmune liver diseases), both the crescent formation in this patient's
      glomeruli and cholangiolitis in his liver may have shared the common etiology
      related to ANCA.

PMID- 10897677
TI  - [Cognitive dysfunction in schizophrenia--analysis using exploratory eye
      movements].
AB  - Studies of exploratory eye movements on patients with schizophrenia were
      reviewed. Cognitive dysfunction in schizophrenia was examined from two aspects:
      the schema by Neisser, and the reaction to an object or a stimulus using
      exploratory eye movements. The schema by which subjects view an object with a
      spacial spread and with a sequence of time was disturbed in schizophrenia
      patients, and this schema was not changeable in the response to various
      conditions in these patients compared with non-schizophrenic individuals. The
      responsive search score (RSS) in schizophrenia was extracted as the disturbance
      of schema in the interpersonal setting. The lowering of RSS was a common feature
      in many patients with schizophrenia and remarkably reflects a trait of
      schizophrenia. We discussed a relationship between the RSS and other trait
      markers in schizophrenia, and it was suggested that the concept of "Disturbance
      of Schema" can explain abnormal results of other indicators and can lead us to
      understand several theories of cognitive dysfunction in schizophrenia.

PMID- 10897678
TI  - [The mental health of school children after the Great Hanshin-Awaji Earthquake:
      I. Epidemiological study and risk factors for mental distress].
AB  - We conducted surveys to study the magnitude and nature of psychological
      consequences of school children affected by the Great Hanshin Awaji Earthquake,
      which occurred in Kobe on January 17th, 1995. It measured 7.2 in magnitude,
      killed more than 6000 people and destroyed at least 170,000 buildings and houses.
      The investigations were carried out 4 months following of the disaster. SUBJECTS:
      About 9000 school children in the 3rd grade, the 5th grade, the 8th grade living
      in the disaster areas. About 2000 children living in distant areas were also
      surveyed as control subjects. METHOD: The questionnaire was in a self-descriptive
      format and consisted of 10 items regarding situation and behavior when the
      earthquake occurred and 22 items about mental health condition. The responses
      were rated from 1 to 4 depending on the frequency of the symptoms, and
      statistically analyzed. RESULT: By factor analysis, three factors were elicited.
      Factor 1 was interpreted as being related to fear and anxiety, factor 2 as
      related to depression and physical symptoms, and factor 3 as related to pro
      social tendencies. The highest mean score of factor 1 was associated with the
      most heavily damaged areas. Less severe damage was associated with a lower mean
      score, and the control areas showed the lowest score. These results show that the
      children in the damaged areas were strongly affected. Factor 2 shows a different
      pattern from factor 1. The score of heavily damaged areas is conspicuously high.
      However, the differences between the other areas were not significant, the
      control areas had scores almost the same as these of the slightly damaged areas.
      These results may mean that in less damaged areas than in more heavily damaged
      areas, there was a more remarkable "heroic phase" after the disaster, which hid
      depressive moods and lasted longer than in the more severely damaged areas, where
      people had to face stern reality in the early stages. Factor 3 shows the reverse
      pattern of factor 2. The slightly damaged areas had the highest score. This
      result also shows the influence of the "heroic stage". As for the mean scores of
      factors 1 and 2, younger children showed higher scores. There were no differences
      in the scores of factor 3 between students in the 3rd grade and 5th grade. The
      score of the students in the 8th grade was the lowest among all. It can be seen
      that adolescents generally lessen their consideration for society as a
      developmental stage in their growth. All of the mean scores of factors 1, 2 and 3
      of females are higher than those of males. In the heavily damaged areas, factor 1
      is associated with an experience of being rescued and injuries of the children
      themselves. Factor 2 is associated with injuries of the children themselves. In
      the moderately damaged areas, factors 1 and 2 are associated with injuries of the
      children themselves and taking in victims in the children's homes. In the
      slightly damaged areas, factor 1 is associated with injuries within families.
      Factor 2 is associated with injuries within families and taking in victims in the
      childrens' homes. CONCLUSIONS: School-aged children exposed to a high-magnitude
      natural disaster had 3 categories of emotions: "fear and anxiety," "depressive
      mood and physical symptoms" and "pro-social tendency." The severity of disaster,
      younger age, and female gender were high risk factors for distress. In the
      heavily damaged areas, an experience of being rescued and injuries of the
      children themselves had a great influence on the mental health of children. In
      lesser damaged areas, taking in victims in the childrens' homes and injuries
      within families had an influence.

PMID- 10897679
TI  - [The mental health of school children after the Great Hanshin-Awaji Earthquake:
      II. Longitudinal analysis].
AB  - We conducted surveys to investigate the nature of the recovery processes and
      psychological reactions of children and adolescents affected by the Great Hanshin
      Awaji Earthquake. The investigations were carried out 4 times at 4 months, 6
      months, one year and two years after the disaster. SUBJECTS: About 9000 school
      children in the 3rd grade, the 5th grade, the 8th grade living in the disaster
      area. METHOD: The questionnaire consisted of 9-12 items regarding situation and
      behavior when the earthquake occurred, and 22 items regarding mental health
      condition, and was filled out in the classroom under supervision by the teacher
      in charge. The responses were rated from 1 to 4 depending on the frequency of the
      symptoms, and statistically analyzed. RESULTS: By factor analysis, three factors
      were elicited. Factor 1 was interpreted as being related to fear and anxiety,
      factor 2 as related to depression and physical symptoms, and factor 3 as related
      to pro-social tendencies. These 3 factors were distinct and stable throughout all
      4 surveys and each of them showed unique recovery processes. The mean score of
      factor 1 was highest at 4 months after the earthquake, and decreased as time
      passed. This factor shows that fear and anxiety seem to be directly related to
      the experience of the earthquake. According to the severity of the disaster, more
      severe damage brought about a higher mean score of factor 1. Furthermore, younger
      children and girls were more strongly affected. Each of the differences in the
      severity of disaster, in age, and in gender decreased as time passed. The mean
      score of factor 2 peaked at 6 months, and it slightly recovered after one year.
      However, the score at the 1st year was still higher than that of the 4th month.
      At two years the score returned to almost the same level as that of the 4th
      month. We think that factor 2, involving depressive mood and psychophysical
      symptoms, may be a secondary phenomenon to fear and anxiety. Other possibilities
      are that they may be caused by environmental changes after the disaster,
      inconveniences of daily life, loss of jobs of parents, or masked by hypomanic
      mood which covered over the disaster area soon after the earthquake (so-called
      heroic phase). Older children have a greater tolerance for depressive mood and
      psychophysical symptoms, but those symptoms occurring in older children have a
      tendency to continue for a longer time. Girls are more heavily affected and need
      more time to recover from trauma than boys. The mean score of factor 3 showed a
      gradual decrease as time passed. There was no difference in the way of decrease
      according to the severity of disaster, age and gender. It may be natural that,
      since the interest in the earthquake decreased as time passed, consideration for
      the victims decreased. CONCLUSIONS: The problems of mental health of children and
      adolescents after the disaster may consist of at least 2 different components;
      "fear and anxiety," which appeared just after the disaster and decreased earlier;
      "depressive and psychophysical symptoms" appeared later and stayed longer.

PMID- 10897680
TI  - [Clinical features of recent methamphetamine abusers: comparison between smoking
      abusers and injection abusers].
AB  - The author studied the clinical features of recent methamphetamine (MAP) abusers
      in Japan by comparing two methods of MAP use: smoking and injection. Of all the
      methamphetamine abusers that consulted Kanagawa Prefectural Center of Psychiatry,
      Serigaya Hospital, between June '97 and November '98, 67 patients that the author
      interviewed and treated were selected to participate in this study. The subjects
      consisted of two groups: 31 smoking abusers and 36 injection abusers. The results
      clearly showed the following: 1. Injection abusers tended to abuse organic
      solvents in addition to MAP, and had criminal records, lower education, and
      alcoholic parents more often than smoking abusers. On the other hand, smoking
      abusers tended to abuse cannabis, and lived in an environment similar to the
      general population. 2. Smoking abusers could not control MAP use, and developed
      acute psychotic symptoms such as hallucinations and delusions more quickly than
      injection abusers. 3. No remarkable differences in psychotic symptoms at acute
      intoxication among the two groups were seen; however, injection abusers showed
      more auditory hallucinations at first consultation. 4. No remarkable differences
      in the percentage of prolonged/chronic psychosis were detected among the two
      groups; however, injection abusers with psychosis needed higher doses of
      neuroleptics. 5. The families of smoking abusers attended family seminars more
      than those of injection abusers; however, there were no remarkable differences in
      the prognosis of the addiction rehabilitation program between the two groups.
      Based on the results, the author proposed a new type of MAP abuser was generated
      when smokable MAP was introduced to Japan. Furthermore, it was found that
      smokable MAP is more likely to cause loss of control and acute psychosis.
      However, this speculation was solely based on observation and treatment of
      abusers who sought consultation at medical facilities, and numerous smoking
      abusers who have not received treatment are considered to exist.

PMID- 10897681
TI  - [Molecular biology of germinal center: a novel cell proliferation-related protein
      in immune system].

PMID- 10897682
TI  - [Sex determination of higher plants].

PMID- 10897683
TI  - [A new cytokine-receptor recognition scheme revealed by the complex structure of
      G-CSF and its receptor].

PMID- 10897684
TI  - [The high-affinity choline transporter].

PMID- 10897685
TI  - [A crucial role of tetraspanin, CD9 in fertilization].

PMID- 10897686
TI  - [Regulation of axonal growth cone motility by neural cell adhesion molecules: L1
      intracellular trafficking and signaling pathways].

PMID- 10897687
TI  - [DNA damage-induced signal pathway of p53 as a tumor suppressor and the gene
      mutation in human cancer].

PMID- 10897688
TI  - [Tobacco mosaic virus: pioneering research for a century].

PMID- 10897689
TI  - [Cell adhesion and detachment control toward cell sheet engineering utilizing
      temperature-responsive intelligent culture dishes].

PMID- 10897690
TI  - [Introduction to ion cyclotron resonance mass spectrometry and it's application].

PMID- 10897691
TI  - Education report needed to be more prescriptive.

PMID- 10897692
TI  - Government misses the point on residential care.

PMID- 10897693
TI  - Professional misconduct case studies. Case 12: Poor interprofessional
      collaboration. Lack of respect shown to a terminally ill patient and his family.

PMID- 10897694
TI  - A surgical approach for patients with endstage emphysema.
AB  - For patients with emphysema who experience deteriorating lung function and
      concomitant comorbidity, there has been little to offer apart from best
      supportive care and more recently pulmonary rehabilitation. The early promise of
      lung transplantation for these patients has failed to materialize--a shortage of
      donors has meant that younger patients are more likely to receive donor lungs. A
      renewed interest in lung volume reduction surgery (LVRS) appears to offer hope
      for selected patients. This article looks at the history of LVRS and illustrates
      its benefits with a case study. However, if LVRS is a clinically significant
      approach to the treatment of emphysemic patients, then it requires careful
      clinical trials so that its benefits and costs can be fully evaluated.

PMID- 10897695
TI  - Radiation-induced reactions. 1: An examination of the phenomenon.
AB  - In this article, the first in a series of three, the author examines the
      phenomenon of radiation-induced skin reactions. This includes a description of
      the theoretical aspects of radiation and its effect on the skin, the prevalence
      and significance of skin reactions seen in clinical practice and a summary of the
      assessment tools that have been used in their evaluation. From this information,
      an analysis of the key signs and symptoms of radiation-induced skin reactions is
      presented. These clinical indicators and descriptors are then available to be
      used as the basis for the development of a comprehensive yet specific assessment
      tool. In part two, these descriptions are integrated into an assessment tool to
      measure radiation-induced skin reactions and the radiation-induced skin reaction
      assessment scale (RISRAS) is described. In part three the methods and results
      from the initial evaluation of the RISRAS are reported.

PMID- 10897696
TI  - Validity of the Walsall Community Pressure Sore Risk Calculator.
AB  - The Walsall Community Risk Score Calculator has been in use for the past 8 years.
      Outcomes from a trust-wide prevalence audit identified that this assessment tool
      may benefit from re-evaluation. This study examined the tool's validity and
      reliability and has resulted in some changes being made to the original score. To
      assess validity, a cross-sectional study of 720 patients was undertaken looking
      at the incidence of pressure damage, despite intervention, over a 12-week period.
      Using logistic regression analysis new weightings for each category were
      developed. This also led to the removal of one factor (bodily pain) which did not
      appear to contribute to increased risk of pressure damage. The updated score
      shows an improved prediction of pressure sore development compared with the
      existing method.

PMID- 10897697
TI  - Phase 1 studies: the development of new dressing technology.
AB  - This article describes the use of phase 1 studies in the research process when
      developing new dressing technology. A phase 1 study refers to the first time that
      humans are exposed to a new therapy. In general, participation is open to healthy
      volunteers only. Phase 1 studies are an essential element in the research process
      and are used to test the safety of a new product. In this study, volunteers were
      patch tested on broken skin to assess whether they were sensitive to a new
      product.

PMID- 10897698
TI  - Is there a risk of cross-infection from laundered reusable bedpads?
AB  - The risk of cross-infection from reusable incontinence bedpads was assessed by
      determining their microbial content after one night's use by incontinent adults
      and after laundering using the standard foul wash procedure specified by the NHS
      Executive (NHS E, 1995) (which includes heat disinfection at 71 degrees C for 3
      minutes). Measurements were made on a total of 145 bedpads from five different
      product designs. It was found that effective laundering destroyed all known
      pathogenic organisms, although some commensal flora were isolated in small
      numbers (mean 12.2 colony forming units/ml). It is concluded that laundering
      reusable incontinence pads using the foul wash procedure leaves pads safe for
      multiple patient reuse with no demonstrable risk of cross-infection.

PMID- 10897699
TI  - Treatment of a patient with a deep leg ulcer using Biatain Adhesive.
AB  - This article looks at the use of Biatain Adhesive, a new foam dressing from
      Coloplast which is manufactured by incorporating 3D polymer structures within the
      central pad. It is now available on the Drug Tariff. The article discusses the
      treatment of exuding wounds and highlights the benefits of Biatain Adhesive by
      focusing on the case of an 84-year-old woman who had a history of long-standing
      leg ulcers where previous dressings had failed to promote healing.

PMID- 10897700
TI  - NaturCare from AlphaMed: the non-scented ostomy deodorant.
AB  - NaturCare is an ostomy deodorant manufactured and distributed by AlphaMed.
      Currently, it is the only non-scented deodorant available on prescription. Odour
      can be extremely stressful to both the person with a stoma (ostomist) and those
      involved in their care. Since NaturCare has no artificial scents added to its
      formula, it can be extremely helpful to those who find the odour embarrassing.

PMID- 10897701
TI  - Investing in practice: enquiry- and problem-based learning.
AB  - Enquiry-based learning (EBL) and problem-based learning (PBL) are two similar
      methods of educating nurses and midwives which have been recommended by the UKCC
      in its new report 'Fitness for Practice' (UKCC, 1999). The integration of theory
      and practice within the student programme is the key to bridging the
      theory/practice gap. The incorporation of EBL and PBL into the curriculum may
      help resolve this gap. As these methods of education foster learning through the
      use of real client scenarios it is important to stress that the partnership
      between clinical and academic staff is of paramount importance. This article
      explores EBL and PBL from the practitioner's perspective and examines some of the
      factors necessary for its successful implementation.

PMID- 10897702
TI  - Confidentiality. 8: Role of the NHS trust and patient confidentiality.

PMID- 10897703
TI  - Peach report reaffirms traditional nursing values.

PMID- 10897704
TI  - Nurses must be wary of their role in walk-in clinics.

PMID- 10897705
TI  - 'Alert' letters and the issue of public protection.

PMID- 10897706
TI  - Case 13: Interim suspension. Nurse who prescribed adult doses of drugs to a
      child.

PMID- 10897707
TI  - Educational preparation: specialist practice in continence care.
AB  - Contributing factors to effective continence service provision include funding,
      organization, and expert knowledge among the individuals providing care. Expert
      knowledge can be gained through clinical experience and appropriate ongoing
      education. It has been widely reported that undergraduate education in this area
      for nurses, doctors and physiotherapists is limited (Brocklehurst, 1990;
      Swaffield, 1994; Laycock, 1995). Many nurses providing continence care have
      accumulated knowledge through experience and trial and error. Little is known
      about the effectiveness of advanced postgraduate education of 'experts' in
      continence care. This article outlines a continence education module developed to
      prepare a specialist group of nurses to provide a high standard of continence
      care that is both safe and effective in a clinical environment. This module was
      designed and evaluated specifically as part of the Leicestershire Medical
      Research Council (MRC) Incontinence Study. Changes in continence knowledge,
      attitudes to research, and acceptability of the module have been explored. When
      setting up a new nurse-led continence service, it is of great importance to
      systematically detail the components of the educational preparation of the nurses
      providing the service. Open discussion of any problems in the design and
      implementation of this module may inform future modules in this and other areas.

PMID- 10897708
TI  - Radiation-induced skin reactions. 2: Development of a measurement tool.
AB  - Radiation-induced skin reactions occur commonly in clinical practice and cause
      various problems for the patient. Assessment and treatment of these reactions is
      an important part of the healthcare professional's role in the radiotherapy unit.
      To accomplish this effectively a specific, yet comprehensive, measuring tool is
      needed. The first article in this three-part series (Vol 8(17): 1134-40) examined
      the phenomenon of radiation-induced skin reactions, including descriptions of how
      radiotherapy affects the skin and the prevalence and significance of these skin
      reactions. Using the literature, the most common signs and symptoms were
      isolated. This provided the basis for the development of a specific yet holistic
      assessment tool. In this article, an explanation of the methods used to collect
      and analyse data for the development of an assessment tool to measure radiation
      induced skin reactions is described. The tool is called the Radiation-Induced
      Skin Reaction Assessment Scale (RISRAS). In the third article in the series, the
      results of RISRAS's initial evaluation is reported along with its efficacy for
      clinical practice.

PMID- 10897709
TI  - Infection control: public health, clinical effectiveness and education.
AB  - In this article the author discusses three main issues in infection control: the
      development of clinical effectiveness, education and public health. Present day
      infection control practice is based on principles put forward by Florence
      Nightingale over 100 years ago. Despite medical advances, hospital-acquired
      infection remains a major cause of morbidity and mortality. Further research is
      required to assess how effective present day infection control activities and
      policies are in reducing the spread of infection. The success of implementing
      evidence-based practice relies on multidisciplinary, user-friendly educational
      initiatives. It is imperative that community practitioners are involved in the
      promotion of infection control. Greater public awareness of infectious agents and
      the importance of basic hygiene will ensure that infection control cannot remain
      the exclusive property of hospitals, but must extend to all areas of public
      health.

PMID- 10897710
TI  - Improving primary health care for people with learning disabilities.
AB  - 'Signposts for Success' (Department of Health (DoH), 1998a) states that
      specialist learning disability services (SpLDS) must promote liaisons with, and
      offer specialist advice to, primary healthcare teams (PHCTs). With the advent
      primary care groups (DoH, 1998b), genuine collaboration and partnership-forging
      is necessary and timely to prevent people with learning disabilities being
      excluded from healthcare services. The project described in the article had three
      broad aims: first, to establish a practice register of people with learning
      disabilities in all practices involved in the project; second, to enable practice
      nurses (PNs), with support, to carry out a systematic health check within the
      practice of people with learning disabilities; and third, to enable the project
      nurse to act as a crucial link between SpLDS and the PHCT. The health checks
      highlighted unmet health and social needs, which were then met through
      appropriate referral and intervention, mainly to specialist services. Follow ups
      were conducted to measure any health gain as a result of the applied
      Interventions. Evidence of health gain was revealed, pointing to the clinical
      effectiveness of performing such checks within the PHCTs.

PMID- 10897711
TI  - Eco-maps: facilitating insight in learning-disabled sex offenders.
AB  - The assessment of risk in relation to men who have learning disabilities and who
      sexually offend can be difficult as innovative means for eliciting information or
      presenting it to them require careful consideration. A risk assessment model has
      been designed which introduces an interactive tool called an 'eco-map' as a means
      of gathering important information from the offender as well as presenting the
      identified risks. The author explores the use and development of the eco-map from
      its crude beginnings to its use in practice. The tool enables offenders to
      rationalize and understand the often complicated concepts which contribute to
      their behaviour and allows them to be actively involved in the risk assessment
      process.

PMID- 10897712
TI  - Case study approach to peripherally inserted central catheters.
AB  - This article looks at the referral of a patient (Mr H) for parenteral nutrition
      and the subsequent insertion of a peripherally inserted central catheter (PICC)
      by the nutrition nurse (NN). It explores the issues directly related to the PICC
      insertion including the route of intravenous access, the ability of the NN to
      insert the PICC, preparation, communication and consent, and prevention of the
      mechanical and septic complications of insertion. This case study demonstrates a
      good technical mastery of PICC insertion in relation to the issues raised. Mr H
      was satisfied with his care, offering positive feedback at follow-up visits to
      clinic. Critical analysis of the case study also revealed implications for
      further development of the role of the NN in ordering the check X-ray and the
      development of evidence-based standards and guidelines related to this procedure.

PMID- 10897713
TI  - Role of the cardioprotective diet in preventing coronary heart disease.
AB  - Diet is a significant feature in the prevention of primary and secondary coronary
      heart disease (CHD). Obesity management is crucial because of its direct
      influence on many CHD risk factors, angina symptoms and capacity to exercise.
      Much evidence is available on the best dietary and nutritional intake for maximum
      cardiac protection. The dietary habits enjoyed by the Mediterranean countries
      appear to confer the best health benefits. These involve eating plenty of fruit,
      vegetables, pulses, nuts, cereal products, olive oil and fish and only small
      amounts of meat and dairy foods. The Mediterranean diet does not contain the
      amounts of animal fats, margarines, cakes, sweets, biscuits and manufactured
      foods that are characteristic of the British diet. Nurses, in their professional
      capacity, can motivate and support patients to change their eating habits.

PMID- 10897714
TI  - The experience of therapeutic touch from a nursing perspective.
AB  - This article describes the phenomenon of therapeutic touch (TT). Similarities and
      differences in the experience of the phenomenon from the perspective of a novice
      practitioner and healthy volunteers are highlighted. A qualitative analysis of
      findings indicates that the experiences of giving and receiving TT can be
      classified within two categories: the cognitive (knowing in the widest sense);
      and conative (instinct and feeling). The key constructs which emerged in this
      study are associated with feelings such as tingling, warmth, coolness, comfort,
      peace, calm and security. Formulation of the two main categories, cognitive and
      conative, emphasize the relationship associated with what is known by the mind
      and instinctively felt by the body. The holistic aspects associated with the
      phenomenon of TT are confirmed in the therapeutic relationship which can be
      formed between the practitioner and recipient during the administration of TT. It
      is suggested that TT, when provided by the nurse in the clinical setting, can
      promote feelings of comfort, peace, calm and security among patients.

PMID- 10897715
TI  - Nurse consultants herald new era for clinical nursing.

PMID- 10897716
TI  - Reflecting.

PMID- 10897717
TI  - Electrical stimulation and pulsed electromagnetic energy: differences in opinion.

PMID- 10897718
TI  - HHRGs: does it hurt too bad to laugh?

PMID- 10897720
TI  - Wound care in Scandinavia.

PMID- 10897719
TI  - Defining extraordinary care.
AB  - Criteria-based protocols are an ethically appropriate strategy to addressing
      issues such as allocation of scarce resources; however, protocols can conflict
      with the ethical ideal of respect for individual autonomy. This article
      illustrates the conflict that can occur between individual patient situations and
      standardized criteria-based protocols. Furthermore, ordinary care and treatment
      outlined in criteria-based protocols can become extraordinary in some cases. The
      case study presented illustrates why it is important to distinguish between
      ordinary and extraordinary care in some situations. The distinction between the
      two is described herein.

PMID- 10897721
TI  - Like a terrorist.

PMID- 10897722
TI  - Living with a chronic wound: the voices of sufferers.
AB  - As the American population continues to age and people live longer, a growing
      number of individuals have chronic health problems. Of these health problems,
      chronic wounds are among the costliest. The focus of this research was to
      understand the meaning of having a nonhealing wound. Heideggerian hermeneutics-
      one of several approaches to interpretive scholarship--was used in this study.
      Through interpreting language or texts, Heideggerian hermeneutics seeks to reveal
      meanings. In this study, the researchers interviewed 10 participants with chronic
      wounds and performed data analysis of the transcripts using qualitative software,
      and then Diekelmann's framework of Heideggerian hermeneutical analysis. Two
      constitutive patterns with six themes emerged from the data--"contending with the
      wound" and "staying home; staying back." Profound themes of oozing and smelling,
      losing sleep, being in pain, and noticing are described in the participants own
      words in the text. By listening to the participants' stories and understanding
      what it is like to live with a chronic wound, healthcare providers can create
      caring contexts.

PMID- 10897723
TI  - Comprehensive care: the healthcare provider's perspective.
AB  - A paradigm shift, or change in worldview, is currently occurring in which clients
      are being comprehensively viewed within the environmental context. This shift
      addresses both mind and body in client care and views healthcare providers as
      part of the environment. Wound care specialists can refine and extend their
      practice by: a) using concepts from comprehensive care and holistic nursing, b)
      focusing on the outcome and process of delivering care, and c) caring for
      themselves in a comprehensive manner. This article describes the author's
      development as a comprehensive and holistic healthcare provider and the impact of
      comprehensive care on her practice.

PMID- 10897724
TI  - Beyond the pressure ulcer blame game: reflections for the future.
AB  - The concept of skin wounds caused primarily as a result of external physical
      forces has been the focus of many healthcare professionals for decades.
      Unfortunately, some of the choices made regarding the definition, description,
      and topical management of pressure ulcers hampers the appreciation of the
      complexity of issues that generally accompany the occurrence of these wounds. As
      the healthcare industry increasingly focuses on quality and accountability,
      industry watchdogs continue to develop metrics to evaluate quality of care while
      legal professionals demand more accountability for healthcare interventions. The
      management of pressure ulcers is often scrutinized and many healthcare providers
      are often unfairly accused of neglect. The occurrence of pressure ulcers, when
      viewed as a failure of the healthcare system, prevents the comprehensive and
      constructive attention this topic deserves. Therefore, as wound care providers,
      we must change the image of pressure ulcers and provide a more balanced portrayal
      of the influences, treatments, and likely outcomes of these wounds. We must
      separate fact from fiction and reality from the psychological reaction that
      pressure ulcers evoke. It is now time to recreate a dialogue for pressure ulcers
      that is productive, realistic, and likely to result in the advancement of care.

PMID- 10897725
TI  - [A 3-day fair and the possibilities it offers: Elder Care 2000 and the Day of
      Geriatrics].

PMID- 10897726
TI  - [Geriatric care 1999: training in nursing needs new ideas].

PMID- 10897727
TI  - [New nursing perspectives, Bremen, 1999: teaching self esteem--knowledge and care
      management].

PMID- 10897728
TI  - [Performing blood transfusion: consideration of ethical aspects].

PMID- 10897729
TI  - [The Robath therapeutic concept assures quality of training].

PMID- 10897730
TI  - [When the "motor of life" is on strike: nursing care in heart surgery--a new
      specialty is presented].

PMID- 10897731
TI  - [Nursing care of brain damaged patients. 2. To provide security and
      satisfaction].

PMID- 10897732
TI  - [Family care: incorporating nursing care into the family].

PMID- 10897733
TI  - [Pediatric clinics in the 21st century: between competition and cooperation].

PMID- 10897734
TI  - [More than just a conversation: a cooperative discussion between coworkers].

PMID- 10897735
TI  - [A model project of the "Patient Information Center": growing up aided by
      professional counselling].

PMID- 10897737
TI  - [Developing and encouraging self esteem: laziness and being well fed do not
      encourage changes in character].

PMID- 10897736
TI  - [Law to improve health care: Health Reform 2000 and implications for the hospital
      system].

PMID- 10897738
TI  - [Creativity in professional life.... Desire to create and pleasure of doing it].
AB  - The human being transforms the rules into actions by using new norms for his
      work. He transgresses the initial standards to apply them to real life. In the
      job of radiology manipulation, creativity is in the heart of the ingenuity which
      would constitute, in a way, the moving force of the profession, the intelligence
      of the body, the cunning intelligence. Explaining the work is therefore difficult
      and complex because the visibility spaces are informal spaces, a mixture of fear
      and of need to show. Creativity, as the binder of the standards jigsaw, adds
      value to the knowledge and, step by step, makes it more useful.

PMID- 10897739
TI  - [The focus of discipline in nursing: clarification with ontologic basis].
AB  - The discipline of nursing is enhanced by the contributions of theoricians,
      researchers and practitioners in nursing who created ways that promote the
      knowledge development of nursing. The contribution of ontology allows for the
      clarification of the nature of reality from which stem the visions about
      phenomena to be studied. In nursing sciences, these visions are embedded in two
      different paradigms that influence the nature of the focus of the discipline as
      well. Some statements about the focus of the discipline are analysed and rules
      allowing for the choice of a coherent heuristic mode are set forth according to
      the chosen paradigm. The coexistence of paradigms deserves the respect of the
      different visions and the engagement to evaluate the theories of the discipline
      in relation with the values grounding our service to the society.

PMID- 10897740
TI  - [Hardiness, coping and quality of life of nurses working in intensive care
      units].
AB  - The goals of the study are two-folds: on the one hand, to examine the relations
      between hardiness, coping strategies and quality of life at work of french nurses
      working in the intensive care units; on the other hand, to examine the mediating
      effect of coping strategies between hardiness and quality of life at work. Data
      was collected using a self-administered questionnaire, anonymously filled by 137
      nurses which represented 60% participation from the initial sample population.
      Maddi & Kobasa's theory (1984) of Hardiness is the foundation for the present
      study and Baron & Kenny's statistical model (1986) was used to determine the
      mediating effect of the coping strategies. Regression analysis demonstrated that
      positive reevaluation/problem solving strategies had a mediating effect between a
      sense of commitment, a sense of mastery and quality of life at work. These
      results prompted various propositions in order to improve nurses quality of life
      at work.

PMID- 10897741
TI  - [The perception of postoperative pain as a stigma on the patient who underwent
      cholecystectomy as well as on the attending nurses].
AB  - Through a descriptive research, we wished to investigate the perception by the
      patients who underwent a cholecysectomy and by the caregivers, of the post
      operative pain in its sociological dimension. The question of the research is as
      follows: How far is the post-operative pain perceived as stigmata by the patients
      who underwent a cholecysectomy and by the nurses? The reference framework is
      built up on the basis of a theoretical approach of cholecystectomy and of the
      notions of pain and stigmata. We carried out interviews with ten patients and ten
      nurses. The sample size does not enable a scientific use of the enquiry results.
      Pain, such as it is perceived by the majority of the patients, as normal and
      acceptable, does not seem to bring them into disrepute. Stigmatization appears in
      the relation caregiver-patient. It contributes to disturbing the flow of
      interactions between the patients and the nurses. When the nurses do not meet the
      expectations of the patients, they are no longer considered as "initiate" but as
      "normal". The affectivity arising in the relationship caregiver-patient, seems to
      have an influence in the management of post-operative pain.

PMID- 10897742
TI  - [Effects of the preparation on anxiety before bronchoscopy].
AB  - In their daily practice, the nurses note the patients' anxiety when they are in
      hospital for diagnosis exams. Considering this observation, we wanted to assess
      the potential benefits provided by the behavioural and relational techniques,
      such as sophrology, maintenance of the help relation, visualization-relaxation.
      In order to carry out this survey, we adopted the model of Betty NEUMAN, who
      relies on the concept of homeostasis and on the stress theory of Hans Seyle. The
      measurement of anxiety by the STAI (State Trait Anxiety Inventory), a scale
      worked out by SPIELBERGER, enabled us to prove that these relational tools, used
      by the nurses, made it possible for the patients to better mobilize their
      adjustment or coping strategies. Recommendations concerning the management of
      anxiety were set out as not to trigger an attitude of vigilant coping.

PMID- 10897744
TI  - [Evaluation of pain in children. Nursing care].
AB  - In conformity with legislation and the present recommendations of public health,
      fight against pain must be a steady concern for the nurses. The authors focus on
      the pain of the children hospitalized in pediatric surgery. The survey carried
      out with the nurses in two services, tries to assess the level at which they
      acknowledge and manage pain. The results highlight the fact that pain care
      remains within the medical area. Few assessment tools are used by the nurses who
      do not objective the concept of pain.

PMID- 10897743
TI  - [Waste management as part of self-care: an in-hospital training?].
AB  - As a health care professional, I feel concerned by the gap existing between urban
      and hospital practice concerning the management of waste, even when it is the
      same objects which are disposed. In the daily practice of the hospital care
      givers, the patients' education is mainly focused on the prevention measures or
      the care techniques to be adopted. The waste dumping modes are very seldom taken
      in consideration, despite the fact that everybody is afraid at the discovery of
      care material abandoned in a public place. That is why the following hypothesis
      was formulated: "The better the patient is educated, the better he will manage
      his self-care waste." The methods used for this diploma work are the documentary
      research and the investigation interviews with all the actors in and out of the
      hospital concerned by the patients' education and/or the management of care
      waste. The pilot study was conducted by means of enquiry questionnaires. It was
      focused on the hospital care givers and on the insulin-dependent diabetic
      patients who practice their self-care, through the enquiry technique "before
      after" The aims of this research were to assess the quality of the education
      given by the hospital care giving staff on the management of self-care waste and
      the impact of this training on the patients. The drawing up of a system of
      reference (at the end of this research investigation work) should enable the
      improvement of the present situation. The small size of the sample used for the
      pilot study did not enable us to invalidate or confirm our working hypotheses.
      But the results obtained during out pilot study showed the bad quality of the
      training given by the hospital care givers and the inadequacy of the patients'
      procedure. That is why our professional project is based on an updating of the
      knowledge of the hospital care givers for the management of the self-care
      material in order to improve the quality of the care given by a hospital team and
      its adequation to the needs of the population at which it is aimed.

PMID- 10897745
TI  - Patient education depends on correct interpretation.

PMID- 10897746
TI  - Computer chairs: invest in a good one.

PMID- 10897747
TI  - Oncology today: new horizons. Prostate cancer.

PMID- 10897748
TI  - Mapping out a clinical pathway.

PMID- 10897749
TI  - Looking for adventure?

PMID- 10897750
TI  - Tetanus--still a problem.

PMID- 10897751
TI  - Through the looking glass: tomorrow's hospital.

PMID- 10897753
TI  - Bedside monitors.

PMID- 10897752
TI  - Hypertensive crisis.

PMID- 10897754
TI  - When a patient bites you.

PMID- 10897755
TI  - Clinical trials. How informed should consent be?

PMID- 10897756
TI  - Managing constipation that's opioid-induced.

PMID- 10897757
TI  - Take this coding challenge.

PMID- 10897758
TI  - Insect stings.

PMID- 10897759
TI  - [Can gene transfer be used to modify the response to radiotherapy?].
AB  - Several recent studies suggest that gene transfer can be combined with
      irradiation to increase anti-tumor efficacy. Among genes of particular interest
      to be used in this combined approach are those involved in the regulation of
      radiation-induced lethality (apoptosis, DNA repair). Some additional aspects
      appear to be relatively specific to these combinations, such as the type of
      vector to be used (anaerobic bacteria) or the type of promoter (radio-inducible
      promoters). The first results obtained in mice bearing human xenograft tumors,
      combining gene transfer and irradiation, are encouraging, but no clinical study
      has been performed so far. Finally it should be pointed out, in this area as well
      as in cancer gene therapy in general, that progress in gene vectorisation is
      mandatory to optimize gene distribution within the tumor.

PMID- 10897760
TI  - [Use of fast neutrons in the treatment of tumors of the salivary glands:
      rationale, review of the literature and experience in Orleans].
AB  - If low LET radiation therapy (photons, electrons), following radical
      microscopically and complete surgery can improve results in term of local control
      from 34 to 74% for salivary gland tumors, local control is more difficult to
      achieve in advanced tumors and only palliative treatment is usually attempted. In
      this survey, all the patient series treated worldwide were reviewed. They show an
      overall control rate of 31% with photon vs 64% with neutron therapy. A
      prospective randomised trial sponsored by the RTOG and the MRC published in 1988
      and reviewed in 1993 showed an overall locoregional complete tumor clearance of
      67% for neutrons and 17% for photons (P < 0.005), with 68% and 25% survival at
      two years for neutrons and photons respectively. This study was closed for
      ethical reasons. In Orleans, since 1987, 59 patients have been treated. At five
      years the persistent local control probability was 69.5%, the five-year crude
      survival probability 66% and the five-year tumor free survival probability was
      64.5%. This review provides evidence that surgical treatment for salivary gland
      tumors should be limited to patients presenting a high likelihood of negative
      surgical margin and a small risk of facial nerve damage. Others patients should
      receive neutron radiation therapy alone as definitive treatment.

PMID- 10897762
TI  - [High dose endobronchial brachytherapy: a curative treatment].
AB  - PURPOSE: New endobronchial techniques of treatment allow a good unblocking.
      Nevertheless, only high dose rate brachytherapy delivers a curative treatment for
      invasive carcinomas. This study analyses the results of the first 33 consecutive
      patients treated with curative intent by this technique from 1994 to 1997, and
      followed-up more than one year. PATIENTS AND METHODS: Thirty-seven lesions were
      treated, with usual schedule delivering 30 Gy at 1 cm depth in six fractions and
      three to five weeks. All the patients were meticulously selected on the local
      involvement of the tumour and absolute contraindications to a surgical treatment.
      All of them have a pulmonary disease history or a general contraindication.
      RESULTS: With a 14-month follow-up, the local control at two months after the
      treatment was 95% (endoscopic and histologic), and 90% of the patients presented
      a prolonged local control. Four patients died of the treated cancer, another of a
      controlateral cancer. Ten patients died of another disease, five of them from a
      respiratory insufficiency. The overall survival rate at two years was 53% and the
      specific survival rate 80%. The acute tolerance was good, without incident.
      Asymptomatic bronchial stenoses, described by endoscopic follow-up, were
      described for seven patients. CONCLUSION: We conclude that, on the basis of a
      good selection of the patients and a respect of the indications, high dose rate
      endobronchial brachytherapy is an effective curative treatment. It offers a new
      curative option and must be proposed for the small invasive carcinomas in non
      operable patients.

PMID- 10897761
TI  - [Radiotherapy and intra-arterial chemotherapy of locally advanced hepatocellular
      carcinoma. Analysis of prognostic factors].
AB  - Prognostic factors in the treatment of local advanced hepatocellular carcinoma
      with radiotherapy, transcatheter arterial embolization and arterial infusion.
      PURPOSE: The treatment effects of radiotherapy and combination modality therapy
      for the local advanced hepatocellular carcinoma (HCC) were retrospectively
      reviewed. MATERIAL AND METHODS: Three hundred and fifty-six patients of HCC (187
      recurrent cases after surgical resection) were treated by 1) radiotherapy only;
      2) Bi-therapeutic method: hepatic artery ligation (HAL) and/or hepatic artery
      embolization (HAE) plus radiotherapy; and 3) tri-therapeutic method (bi
      therapeutic method plus hepatic artery infusion) from 1975 to 1996. Kaplan-Meier
      method has been used to evaluate the survival rates. RESULTS: There were no
      significant differences among these three treatment groups in the symptom relief
      rate, but the mean relief time period was much shorter in radiotherapy alone
      group (2.5 vs 44 months, P < 0.05). A lower tumor response rate was found in the
      radiotherapy alone group (P < 0.05), although that was similar for both primary
      or recurrent tumors (P > 0.05). There were evident differences in five-year
      survivals among these three treatment groups: 0% for radiotherapy alone, 22.8%
      for bi-therapeutic method and 38.8% for tri-therapeutic method (P < 0.01). The
      prognosis was influenced by Okuda classification. CONCLUSION: Non-resectable
      local advanced HCC can be treated by the combination modality therapy, including
      radiotherapy, with a quite high cure rate. Radiotherapy alone can relief the
      symptoms.

PMID- 10897763
TI  - [Effect of Ginkgo biloba extract (EGb 761) on rats in an experimental model of
      acute encephalopathy after total body irradiation].
AB  - PURPOSE: To define the therapeutic effect of Ginkgo biloba extract (EGb 761) in
      an experimental model of acute encephalopathy following total body irradiation in
      rats. MATERIAL AND METHODS: Ninety four-month-old rats received 4.5 Gy total body
      irradiation (TBI) at day 1 while 15 rats received sham irradiation. A behavioural
      study based on a conditioning test of negative reinforcement, the one-way
      avoidance test, was performed test, was performed after irradiation. Orally
      treatment was started one day (study A) or twenty two days (study B) after
      irradiation and repeated daily for twelve days. In the irradiated group, three
      subgroups were defined according to the treatment received: EGb 761 (50 mg/kg),
      EGb 761 (100 mg/kg), water. RESULTS: This work comprised two consecutive studies.
      In study A (45 rats) the one-way avoidance test was administered daily from day 7
      to day 14. In study B (45 rats) the behavioural test was performed from day 28 to
      day 35. Study A (three groups of 15 rats): following TBI, irradiated rats treated
      with water demonstrated a significant delay in a learning the one-way avoidance
      test in comparison with sham-irradiated rats (P < 0.0002) or irradiated rats
      treated with EGb 761 (50 mg/kg; P < 0.0017) or EGb 761 (100 mg/kg; P < 0.0002).
      The irradiated rats, treated with EGb 761 (50 or 100 mg/kg) did not differ from
      the sham-irradiated controls. Study B (three groups of 15 rats): the irradiated
      rats, treated with water or EGb 761 (50 or 100 mg/kg) did not differ from the
      sham-irradiated controls. CONCLUSION: This study indicates that a relatively low
      dose of total body irradiation induces a substantial acute learning dysfunction
      in the rat, which persists fourteen days after TBI. This effect is prevented by
      the administration of EGb 761 (50 or 100 mg/kg) started twenty-four hours after
      irradiation.

PMID- 10897764
TI  - [Dosimetric evaluation of conformal radiotherapy: conformity factor].
AB  - The aim of three-dimensional conformal therapy (3DCRT) is to treat the Planning
      Target Volume (PTV) to the prescribed dose while reducing doses to normal tissues
      and critical structures, in order to increase local control and reduce toxicity.
      The evaluation tools used for optimizing treatment techniques are three
      dimensional visualization of dose distributions, dose-volume histograms, tumor
      control probabilities (TCP) and normal tissue complication probabilities (NTCP).
      These tools, however, do not fully quantify the conformity of dose distributions
      to the PTV. Specific tools were introduced to measure this conformity for a given
      dose level. We have extended those definitions to different dose levels, using a
      conformity index (CI). CI is based on the relative volumes of PTV and outside the
      PTV receiving more than a given dose. This parameter has been evaluated by a
      clinical study including 82 patients treated for lung cancer and 82 patients
      treated for prostate cancer. The CI was low for lung dosimetric studies (0.35 at
      the prescribed dose 66 Gy) due to build-up around the GTV and to spinal cord
      sparing. For prostate dosimetric studies, the CI was higher (0.57 at the
      prescribed dose 70 Gy). The CI has been used to compare treatment plans for lung
      3DCRT (2 vs 3 beams) and prostate 3DCRT (4 vs 7 beams). The variation of CI with
      dose can be used to optimize dose prescription.

PMID- 10897765
TI  - [In vitro oxygen-dependent survival of 2 human cell lines after radiation
      combined with tirapazamine (SR-4233) and cisplatin].
AB  - Recent data have shown that the in vitro and in vivo cytotoxicity of bioreductive
      drugs could be significantly increased by combination with ionising radiation or
      chemotherapy. Various parameters such as oxygen tension and timing of
      administration of the drugs could play a crucial role in the efficacy of combined
      treatment modalities. The aim of this study was to define the oxygen dependency
      of cell survival after in vitro irradiation and incubation with tirapazamine, a
      bioreductive drug, and cisplatin given alone or simultaneously. Two human cell
      lines were studied: one cell line sensitive to tirapazamine, Na11+, a pigmented
      melanoma with a high percentage of hypoxic cells, and a less sensitive cell line
      to tirapazamine, HRT18, a rectal adenocarcinoma. Gas changes were made to study
      cell survival at four different oxygen concentrations (pO2): air (20.9% O2), 10.2
      and 0.2% O2. Cells were incubated with tirapazamine and cisplatin alone or
      combined for one hour at 37 degrees C, then irradiated and cultured. For Na11+,
      cell survival after irradiation was comparable in air and at 10% oxygen with the
      two drugs given alone or combined. At 2 and 0.2% oxygen, cell killing was largely
      increased by tirapazamine and was not modified by the addition of cisplatin. For
      HRT18, cell survival was not modified when cisplatin was added to radiation,
      whatever the oxygen partial pressure. At low pO2 (2 and 0.2%) the cytotoxic
      effect of tirapazamine was not significantly decreased by the addition of
      cisplatin. When cytotoxic and bioreductive drugs are combined to radiation, the
      magnitude of the observed effect is highly dependent on the partial oxygen
      pressure and on the sensitivity of the cell line to the individual drugs. This
      has very important implications for clinical strategies based on combined chemo
      radiotherapy.

PMID- 10897766
TI  - [Standards, options, and recommendations for radiotherapy of kidney cancer].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR), initiated in 1993,
      is a collaborative project between the Federation of the French Cancer Centres
      (FNCLCC), the 20 French Cancer Centres and specialists from French Public
      Universities, General Hospitals and Private Clinics. The main objective is the
      development of clinical practice guidelines to improve the quality of health care
      and outcome for cancer patients. The methodology is based on literature review
      and critical appraisal by a multidisciplinary expert group, with feedback from
      specialists in cancer care delivery. OBJECTIVES: To develop clinical practice
      guidelines for the diagnosis, management and treatment of patients with renal
      cancer. This review is part of previously published complete guidelines and
      focuses on the place of radiotherapy in this disease. METHODS: The data was
      identified by literature search using Medline (up to June 1999) and personal
      reference lists. The main endpoints considered were survival, risk factors for
      late effects of radiotherapy, safety and quality of life. RESULTS: The key
      recommendations are: 1) In localised renal cancer, adjuvant radiotherapy has a
      limited role: it is not indicated for T1 and T2 tumours and there is no proof of
      a survival benefit for T3 N1-N2 tumours. Postoperative radiotherapy can be
      considered in young patients without risk factors for the development of post
      radiotherapy complications and without loco-regional invasion (renal capsule,
      renal pelvis, vena cava, regional lymph nodes); 2) For metastatic tumours, the
      multidisciplinary team must decide whether palliative radiotherapy is appropriate
      after consideration of the prognostic factors. An isolated metastasis can be
      treated by radiosurgery and stereotaxic radiosurgery may be of benefit in the
      case of one or two cerebral metastasis. The optimal dose for palliative treatment
      is not known. Radiotherapy followed by immunotherapy can also be considered if
      the patient has no contraindication to such treatments.

PMID- 10897767
TI  - [Definition of Barrett esophagus].

PMID- 10897768
TI  - [Physiopathology of Barrett mucosa].

PMID- 10897769
TI  - [Barrett esophagus: epidemiology and natural history of tumor progression].

PMID- 10897770
TI  - [Contribution of new tools to the characterization of Barrett mucosa].

PMID- 10897771
TI  - [Surveillance of Barrett esophagus].

PMID- 10897772
TI  - [Objectives and modalities of treatment of Barrett esophagus].

PMID- 10897773
TI  - [Liver transplantation in France. Current and future status, seen by the French
      transplant establishment].

PMID- 10897774
TI  - [Role of liver transplantation in the treatment of viral cirrhosis C].

PMID- 10897775
TI  - [Results and indications of liver transplantation in alcoholic cirrhosis].

PMID- 10897776
TI  - [Follow-up of liver transplantation].

PMID- 10897777
TI  - [Alternatives to liver transplantation].

PMID- 10897779
TI  - [What is effective nutritional therapy in digestive disease?].

PMID- 10897778
TI  - [Intestinal transplantation].

PMID- 10897780
TI  - [Lactose in diets used for digestive disorders].

PMID- 10897781
TI  - [Vitamins in digestive diseases].

PMID- 10897782
TI  - [Gluten-free diet and celiac disease in adults].

PMID- 10897783
TI  - [Residue-free diet: definition, indications].

PMID- 10897784
TI  - [Is dietary fiber useful in intestinal functional diseases?].

PMID- 10897785
TI  - [Diet and colorectal carcinogenesis: recent data].

PMID- 10897786
TI  - [Endoscopy of chronic intestinal inflammatory diseases: basic semiology and
      usefulness for diagnosis].

PMID- 10897787
TI  - [Endoscopy of chronic inflammatory intestinal diseases: importance for
      surveillance].

PMID- 10897788
TI  - [Cytokines and anti-cytokines in chronic inflammatory intestinal diseases].

PMID- 10897789
TI  - [Corticoids in intestinal inflammatory diseases: use].

PMID- 10897790
TI  - [Use of immunosuppressors in chronic inflammatory intestinal diseases].

PMID- 10897791
TI  - [Role of antibiotics in Crohn's disease].

PMID- 10897792
TI  - [Diet therapy in chronic inflammatory intestinal diseases: current status and
      perspectives].

PMID- 10897793
TI  - Non-random distribution of the pericentromeric heterochromatin in meiotic
      prophase nuclei of mammalian spermatocytes.
AB  - The central or peripheral distribution of condensed chromatin (CC) was studied in
      pachytene spermatocyte nuclei in Mus domesticus, 2n = 40; Pudu puda, 2n = 70;
      Ctenomys opimus, 2n = 26 and Octodon degus, 2n = 58. Species were chosen
      according to the morphological characteristics of their chromosomal complements
      and in particular, the terminal or medial chromosomal localisation of the
      pericentromeric constitutive heterochromatin. Counts were made by defining the
      areas corresponding to peripheral and central location in each nuclear section
      from a series. The null hypothesis (i.e. random distribution of CC) was rejected.
      In the nuclear sections of Mus domesticus and Pudu puda, 69% and 74% of CC,
      respectively, was found in the peripheral nuclear space, while in those of
      Octodon degus and Ctenomys opimus, 69% and 65% of CC, respectively, was found in
      the central nuclear space. We estimate that if the CC measured in spermatocyte
      nuclei corresponds mainly to pericentromeric constitutive heterochromatin, the
      distribution found is consistent with that expected in accordance with the
      nuclear architecture model for meiocytes (Fernandez-Donoso, 1982; Fernandez
      Donoso & Berrios, 1985). This model proposes a peripheral nuclear localisation
      for pericentromeric heterochromatin of telocentric bivalents and a relatively
      central nuclear localisation for pericentromeric heterochromatin of metacentric
      bivalents. We also discuss some of the biological consequences that could arise
      from the conservation of such distributions.

PMID- 10897794
TI  - Nature and distribution of constitutive heterochromatin in fishes, genus
      Hypostomus (Loricariidae).
AB  - Some Hypostomus species were studied concerning the features of the karyotype
      structure and the constitutive heterochromatin. The karyotype of Hypostomus sp. F
      from the Sao Francisco river (Minas Gerais state, Brazil) is now described for
      the first time. A diversity in the diploid number, ranging from 2n = 68 to 2n =
      80, as well as in the karyotype formulae, is evident in this fish group. Two
      types of heterochromatin, GC- and AT-rich, could be identified with the use of
      base-specific fluorochromes. In some species heterochromatic bands are mainly
      located on the centromeric and telomeric chromosomal regions, while in other
      species they are also observed at interstitial locations. Hypotheses concerning
      this heterochromatic distribution in Hypostomus karyotypes are discussed. A case
      of supernumerary heterochromatic segment and a centric fusion appear to be
      related with two variant karyotypic formulae observed among specimens from the
      Mogi-Guacu and Sao Francisco rivers, respectively. The available data permit us
      to characterize a divergent karyotypic evolution among the Hypostomus species
      already analyzed, both at the macro- and microstructural levels, that is, their
      general karyotype organization and particular features related to chromosomal
      banding or staining, respectively.

PMID- 10897795
TI  - Karyotype characterization of three species of the genus Trichomycterus
      (Teleostei, Siluriformes) from Iguacu river basin.
AB  - Three species belonging to the genus Trichomycterus were collected from Iguacu
      river basin and analyzed from the cytogenetic point of view. Although the species
      studied had the same diploid number 2n = 54 chromosomes and fundamental number
      108, they differed in their karyotypic formulae. C-band patterns showed presence
      of specific-species markers in T. davisi and T. stawiarski. Results of analysis
      from the nucleolus organizer region, obtained by silver nitrate staining and
      CMA3, showed that size heteromorphism observed in this region may be due to gene
      duplication. Evolution aspects of the Trichomycteridae family and the presence of
      B chromosome in T. davisi are discussed.

PMID- 10897796
TI  - Structural and genetic studies of the proliferation disrupter genes of Drosophila
      simulans and D. melanogaster.
AB  - To examine whether structural and functional differences exist in the
      proliferation disrupter (prod) genes between Drosophila simulans and D.
      melanogaster, we analyzed and compared both genes. The exon-intron structure of
      the prod genes was found to be the same--three exons were interrupted by two
      introns, although a previous report suggested that only one intron existed in D.
      melanogaster. The prod genes of D. simulans and D. melanogaster both turn out to
      encode 346 amino acids, not 301 as previously reported for D. melanogaster. The
      numbers of nucleotide substitutions in the prod genes was 0.0747 +/- 0.0180 per
      synonymous site and 0.0116 +/- 0.0039 per replacement site, both comparable to
      those previously known for homologous genes between D. simulans and D.
      melanogaster. Genetic analysis demonstrated that D. simulans PROD can compensate
      for a deficiency of D. melanogaster PROD in hybrids. The PRODs of D. simulans and
      D. melanogaster presumably share the same function and a conserved working
      mechanism. The prod gene showed no significant interaction with the lethality of
      the male hybrid between these species.

PMID- 10897797
TI  - Genomic P elements and P-M characteristics of eastern Australian populations of
      Drosophila melanogaster.
AB  - As part of our effort to monitor changes in the clinical pattern of P element
      associated traits in eastern Australian Drosophila melanogaster, we investigated
      the genomic P elements of 293 isofemale lines collected in the period 1991-1994
      from 45 localities. P elements were present in many copies in all genomes
      examined, with full-size P and KP element size classes accounting for the large
      majority. SR elements were not present in at least 92% of the lines tested. South
      of about 26 degrees south Latitude (degree SLat), the ratio of KP to full-size P
      elements (KP/P ratio) increased, correlating weakly with the P-M phenotypes of
      the populations, from moderately P populations (26-29 degrees SLat) to M
      populations (37-38 degrees SLat). North of 26 degrees SLat, in weak P
      populations, the KP/P ratio was higher than between 26 and 29 degrees Slat. The
      KP/P ratio appears to be higher in the northern populations than it was when
      previous studies were done. Overall, a high KP/P ratio among lines correlated
      roughly with a lack of P activity, but it also correlated with reduced repressor
      function. In a sample of 30 lines, a maternal effect of repressor function did
      not show a pattern with latitude, nor with KP/P ratio, nor with presence or
      absence of P activity.

PMID- 10897798
TI  - Age- and sex-distribution of the mutation load.
AB  - We investigate the age and sex distribution of genetic fitness under mutation
      selection balance by means of simple one-locus two-allele models. We find that
      the extent of age and sex variation in the mutation load is very dependent on the
      average effect of new mutations. If the average heterozygote selective effect of
      new mutations is large, then age and sex differences may constitute a significant
      fraction of the total load, and be significant as compared to standing genetic
      variation. Whether the mutation load will increase or decrease with age depends
      on the age- and sex-specific effects of the new mutations, and on the rate of
      accumulation of mutations in the germ line as individuals age. We argue that the
      load will most likely increase with age in animals with continuous germ-cell
      division throughout life, and that this will occur even when mutations have
      unconditionally deleterious effects. We show that a male-biased mutation rate is
      likely to result in both a male-biased mutation load and a load that increases
      with male age.

PMID- 10897799
TI  - Ribosomal protein S6 cDNA from two Aedes mosquitoes encodes a carboxyl-terminal
      extension that resembles histone H1 proteins.
AB  - Ribosomal protein S6 (rpS6) is the major phosphorylated protein on the eukaryotic
      ribosome. Because electrophoretic evidence suggested that the homolog of rpS6
      from the mosquitoes Aedes albopictus and Aedes aegypti was measurably larger than
      Drosophila rpS6, we have now isolated full-length cDNAs encoding Aedes albopictus
      and Aedes aegypti rpS6. The mosquito rpS6 cDNAs encoded a 100 amino acid
      extension at the carboxyl-terminus, relative to rpS6 from humans and Drosophila.
      This region had homology to cDNAs encoding histone H1 from various species and
      accounted for the larger size of the mosquito protein on polyacrylamide gels. On
      Northern blots, the mosquito cDNA hybridized to a single band measuring
      approximately 1.2 kb.

PMID- 10897800
TI  - L-alpha-glycerylphosphorylcholine enhances the amplitude of the pattern
      electroretinogram in rhesus monkeys. A pilot study.
AB  - The effects of L-alpha-glyceryl-phosphorylcholine (LGPC), a putative
      acetylcholine precursor, were studied on the pattern electroretinogram (PERG) in
      two rhesus monkeys. In the time interval 10-30 min after LGPC administration (85
      mg/kg i.m.), the amplitude of the PERG increased significantly. In both monkeys
      the amplitude enhancement was more pronounced for low spatial frequency stimuli
      (1 cycle/degree) than for medium spatial frequency gratings (5 cycles/degree).
      This result suggests that besides the general facilitatory properties, LGPC may
      have specific spatial frequency tuning effects at the level of retinal
      information processing.

PMID- 10897801
TI  - Long-term portocaval shunt and changes in rat brain amine systems.
AB  - Brain amine system parameters were investigated in Wistar rats sacrificed 7
      months following portocaval shunt or sham operation. After removal of the
      cerebellum and pons, the hypothalamus and remaining parts of the brain were
      examined. Histamine was assayed radioenzymatically; indoles and catechols by HPLC
      with electrochemical detection; spermidine and spermine by HPLC with fluorometry.
      MAO-A and MAO-B activities were estimated with radioassays employing serotonin
      and beta-phenylethylamine, respectively and specific inhibitors, clorgyline and
      deprenyl. Long-term portocaval shunt did not significantly alter cerebral
      catecholamines, serotonin, spermidine or spermine concentrations. However, brain
      histamine and 5-hydroxyindoleactic acid were significantly raised. Of the MAO
      enzymes only MAO-B activity was elevated (ca. 25%, p < 0.05) in the hypothalamus
      but not in the rest of the brain. The kinetic measurements suggest an adaptive
      change in MAO-B protein synthesis. The data suggest changes evoked by portocaval
      shunt in brain amine systems are permanent and there are species differences in
      MAO enzymes' response to higher substrate supply.

PMID- 10897802
TI  - Neural tissue transplant in the lateral hypothalamic lesioned rats: functional
      recovery pattern.
AB  - Transplantation has come of age as an important investigative tool for studying
      normal growth and development of the brain tissue. The present study reports the
      effect of lateral hypothalamic (LHA) lesion and foetal hypothalamic tissue
      transplantation on the feeding behaviour. In a group of rats, LHA was lesioned
      bilaterally by passing direct current. Subsequently, in a separate group of rats,
      foetal hypothalamic tissue was transplanted at the lesioned site. Following LHA
      lesion, all the rats died of aphagia and adipsia within 7 days, whereas, the rats
      in whom foetal hypothalamus was transplanted, started taking food and water in
      small quantities from the first day of transplantation itself. Later, they were
      able to attain their preoperative values. This recovery of the feeding behaviour
      following foetal tissue transplantation may be due to the formation of synaptic
      connections or due to the release of neurotrophic factors.

PMID- 10897803
TI  - beta-Amyloid[1-40]-induced early hyperpolarization in M26-1F cells, an
      immortalized rat striatal cell line.
AB  - The short-term (20-minute) action of beta[1-40]-amyloid on the resting
      transmembrane potential was investigated by means of flow-cytofluorimetric
      studies in M26-1F cells, an immortalized rat striatal cell line, using the
      potential-sensitive fluorescent probe bis-oxonol. The distribution of the
      individual cell-associated probe fluorescence was found to be shifted to lower
      levels in cells treated with beta-amyloid[1-40] for 20 minutes as compared with
      that of their untreated counterparts. A change in the same direction was caused
      by valinomycin, a hyperpolarizing ionophore, whereas gramicidin, a depolarizing
      ionophore, induced a shift to higher fluorescence intensities. These findings,
      together with the reported behaviour of this particular fluorescent probe at
      different transmembrane potential levels, indicate that beta-amyloid[1-40] is
      capable of inducing early hyperpolarization in M26-1F cells. This is one of the
      earliest cell physiological effect of beta-amyloid peptides that has been
      reported so far. Moreover, our findings indicate an ionophore-like action of
      amyloid peptides.

PMID- 10897805
TI  - A light and electron microscopic analysis of the convergent retinal and visual
      cortical projections to the nucleus of the optic tract (NOT) in the pigmented
      rat.
AB  - It is generally known that the nucleus of the optic tract (NOT) subserves
      visuomotor relations between the retina and preoculomotor structures as the only
      subcortical pathway mediating optokinetic responses (OKR) in mammals. We have
      examined the projections from the retina and visual cortical areas (areas 17, 18a
      and 18b) to NOT using tracers (wheat germ agglutinin-conjugated horseradish
      peroxidase, WGA-HRP and cholera toxin B subunit, CTB) in order to clarify how
      these two different functional inputs to OKR are organized. CTB injection into
      the vitreous body resulted in anterograde label almost exclusively in the
      contralateral NOT. Ultrastructually, the size of the retinal axon terminals was
      small (up to 0.7 micron in diameter), contained round synaptic vesicles and pale
      mitochondria, and made asymmetrical synaptic contacts with both GABA-positive and
      GABA-negative NOT neurons. Visual cortical area 17 and the transitional area
      between area 17 and 18a, or between area 17 and 18b projected their axons to the
      ipsilateral NOT. Ultrastructually, the size of the cortical axon terminals was
      small (up to 0.5 micron in diameter), contained round synaptic vesicles, and made
      asymmetrical synaptic contacts only with GABAnegative NOT neurons. With light and
      electron microscopical observation, there was a considerable overlap in the
      cortico-NOT and retino-NOT projection pattern: GABA-negative (presumably NOT
      projection) neurons simultaneously receive input from both cortical and retinal
      terminals. From these results, it seems reasonable to postulate that inputs from
      visual cortical areas in the pigmented rat cooperate with those from the retina
      in controlling OKR.

PMID- 10897804
TI  - Substance P radioimmunoassay for quantitative characterization of sensory
      neurotransmitter release.
AB  - In the present work we report the development of a new radioimmunoassay method
      for measuring the substance P content liberated from isolated rat tracheae in
      response to electrical or chemical (capsaicin, resiniferatoxin, piperine)
      stimulation. The amount of substance P released by electrical stimulation has
      been found to be dependent on the number of pulses and chemically elicited
      substance P release also proved to be dose-dependent. Our findings reinforce
      previous data that resiniferatoxin is approximately 100 times more potent than
      capsaicin and the potency ratio between piperine and capsaicin is 1/50.

PMID- 10897806
TI  - The effect of nitrogen oxide level modulation on the content of thiol compounds
      and anaerobic sulfur metabolism in mice brains.
AB  - Aminoguanidine (AG) an inhibitor of NO-synthase reduces cysteine (Cys), cystine
      (CC), sulfane sulfur (SS) and glutathione (GSH) in brain stems but practically
      has no effects on the levels of reactive oxygen species (ROS). In cortex AG
      decreases to a lower degree the concentration of Cys, CC, GSH but in this brain
      part significantly decreases ROS levels and increases SS. Under the AG action
      cystathionase (CST) activity very seriously decreases in stems and in cortex and
      simultaneously activity of 3-mercaptopyruvate sulfurtransferase (MPST) increases.
      The morpholinosydnonimine (SIN-1) the specific donor of NO and O2 only slightly
      reduces Cys and GSH in brain stems and ROS and SS remain at the control levels.
      Simultaneously, there is an increase in cortex of the amounts of GSH with the
      reduction of ROS and SS. Furthermore, SIN-1 seriously decreases in stems and
      cortex the activity of CST and increases the activity of MPST. These results
      confirmed the relationship between intracellular levels of NO, sulfhydryl groups,
      ROS, and anaerobic sulfur metabolism.

PMID- 10897807
TI  - Opsoclonus-myoclonus and antineuronal antibodies in neuroblastoma.

PMID- 10897808
TI  - Importance of oral antimetabolite "maintenance" therapy in childhood
      lymphoblastic leukemia.

PMID- 10897809
TI  - Hematology and oncology at the Hospital for Sick Children.

PMID- 10897810
TI  - Department of Pediatric Hematology-Oncology in Crete.

PMID- 10897811
TI  - Pediatric oncology in Slovenia.
AB  - Slovenia, a new country and formerly a part of Yugoslavia, has had its Childrens
      Hospital in Ljubljana since 1865. This became a part of the University Hospital
      in 1945, and in the early 1960s the Department of Pediatric Hematology-Oncology
      was established. The Oncological Institute of Slovenia was established in 1938
      and has developed into a modern facility for comprehensive cancer care, research,
      and teaching. In close cooperation, established in the 1960s, a team from these
      two institutions takes care of the approximately 60 children per year who develop
      cancer in Slovenia. Consisting of pediatricians, radiation oncologists,
      pathologists, cytologists, surgeons, and other ad hoc specialists, the team meets
      at least twice weekly to plan treatment, follow the patients, discuss the
      results, and teach. All patients are subject to regular follow-up indefinitely. A
      separate team has been formed to study the late effects of cancer treatment on
      survivors, who by now are mostly adults.

PMID- 10897813
TI  - Granulocyte colony-stimulating factor in neutropenic, pediatric solid tumor
      patients following chemotherapy.
AB  - Granulocyte colony-stimulating factor (G-CSF) has been used to reduce the
      duration and/or degree of neutropenia of different etiologies in recent years. In
      this study, experience with the use of G-CSF (Neupogen, Roche) after 123 courses
      of highly myelosuppressive chemotherapy administered to 31 (20 female, 11 male)
      patients with pediatric solid tumors is reported. G-CSF was initiated at a white
      blood cell (WBC) count of 918 +/- 452/microL (100-2000), at a dose of 7.6 +/- 2.3
      micrograms/kg/d (5-14) subcutaneously for 5.2 +/- 2.4 days (2-18). G-CSF was
      given for afebrile neutropenia after 82 and for febrile neutropenia after 41
      courses. Only in two episodes where G-CSF was given for afebrile neutropenia,
      fever developed. The average hospitalization period for febrile neutropenia was
      9.8 +/- 3.3 days (5-20). Chemotherapy could be given on scheduled time and dosage
      in 90% of the courses in which G-CSF was used for afebrile neutropenia. G-CSF was
      well tolerated. Bone pain was observed in two patients and urticaria in one
      patient. In conclusion, G-CSF increased the WBC count effectively, there were
      only two febrile episodes in 82 courses in children receiving G-CSF for afebrile
      neutropenia, it was well tolerated, and it was found to be feasible for use in a
      developing country.

PMID- 10897812
TI  - Pharmacokinetics of the 5HT3 receptor antagonist tropisetron in children.
AB  - A pharmacokinetic study in children was performed to assess whether the
      pharmacokinetic profile of tropisetron in pediatric patients in similar to that
      in adults. In three pediatric centers, three dosages were tested in two age
      groups during chemotherapy (Group A, 3-6 years, 2, 5, or 20 mg/m2; group B, 7-15
      years, 2, 5, or 20 mg). Children received tropisetron intravenously (course 1) or
      orally (course 2) before the start of chemotherapy. Blood samples were drawn over
      24 hours. Tropisetron treatment continued for up to 6 days at the same daily
      dose, administered orally. Data were available for 45 patients after intravenous
      and for 38 patients after oral administration. 82% of course 1 patients and 72%
      of course 2 patients had no emesis on day 1. Headache occurred in eight patients
      and abdominal symptoms in three patients. Terminal half-life (5.3-6.6 hours),
      tmax (1.4-1.5 hours), and absolute bioavailability (41-42%) were identical in
      both age groups and comparable to those in adults. Because of a smaller volume of
      distribution, group A children showed a higher Cmax/dose (P < .001) and a higher
      area under curve (AUC) dose (P < .05) than adults. All parameters were
      independent of the dose administered. In conclusion, the elimination and absolute
      bioavailability of tropisetron in children are similar to those in adults.
      Because of its age-dependent volume of distribution, tropisetron should be
      administered once a day according to the body surface area in children below 10
      years of age.

PMID- 10897814
TI  - Immune response of immunocompromised children with malignancies to a recombinant
      hepatitis B vaccine.
AB  - The aim of this study was to interpret the antibody response to hepatitis B
      vaccination following an intensified four-dose schedule in 140 cancer patients
      who presented at our clinic between January 1, 1993 and December 31, 1994.
      According to therapy status, the patients were divided into two groups: group A
      consisted of 76 patients undergoing chemotherapy and group B of 64 patients in
      complete remission and off treatment. The eligibility requirements were negative
      hepatitis B virus (HBV), HCV, and human immunodeficiency virus serologic markers.
      A total of four dose (20 micrograms per dose) of recombinant HB vaccine was
      administered intramuscularly in the deltoid region at 0, 1, 2, and 6 months.
      Blood from the vaccinated subjects was obtained at months 1, 2, 3, and 7 in order
      to measure anti-HBs titer levels. Protective anti-HBs titers were considered to
      be those > or = 10 mIU/mL. The overall seroconversion rate 1 month after the
      fourth dose was 57% (80/140 patients), and the seroconversion rates for groups A
      and B were 31.5% (24/76 patients) and 87.5% (56/64 patients), respectively. Our
      results indicated that immunocompromised children undergoing chemotherapy
      (although less responsive than children in complete remission and off treatment)
      still preserved their potential to produce protective titers of anti-HBs. On this
      basis we recommend (1) HB vaccination after diagnosis of malignancy in pediatric
      patients whenever a high prevalence of HB infection exists and (2) vaccination of
      patients of therapy and in complete remission.

PMID- 10897815
TI  - Myelotoxicity, pharmacokinetics, and relapse rate with methotrexate/6
      mercaptopurine maintenance therapy of childhood acute lymphoblastic leukemia.
AB  - White blood cell and absolute neutrophil counts (WBC, ANC), aminotransferase (AT)
      levels, methotrexate (MTX) and 6-mercaptopurine (6MP) doses, metabolites in
      erythrocytes (E-MTX and E-6TGN), and the prognostic significance of these
      parameters were studied in 58 children receiving MTX/6MP maintenance therapy for
      acute lymphoblastic leukemia diagnosed from July 1986 to December 1991. At the
      end of follow-up July 1995, 13 patients had relapsed (pEFS = 0.77). Weighted
      means of AT, WBC, and ANC during and after maintenance therapy (mAT, mWBCON,
      mWBCOFF, mANCON, mANCOFF), E-MTX (mE-MTX), and E-6TGN (mE-6TGN) were calculated,
      as well as the product of mE-MTX and mE-6TGN (mE-MTX*6TGN), as MTX and 6MP
      probably act synergistically. Beyond higher MTX and 6MP doses to patients with
      high mWBCON, neither mWBCON, (median 3.5 x 10(9)/L), mANCON, nor mAT was
      correlated with the dose of MTX and 6MP, mE-MTX, mE-6TGN, or risk of relapse.
      Patients with mE-MTX*6TGN above or below 828 (nmol/mmol Hb)2 (median value) had
      pEFS values of 0.84 and 0.70, respectively (P = .16). All 5 patients who relapsed
      during therapy had mE-MTX*6TGN < 828 (nmol/mmol Hb)2 (P = .03). mWBCOFF and the
      degree of myelosuppression (= mWBCSHIFT = mWBCOFF - mWBCON; median: 2.5 x
      10(9)/L) were related to age (rs = -0.50, P = .001 and rs = -0.40, P = .006,
      respectively). All eight relapses off therapy occurred in patients with mWBCSHIFT
      < 2.5 x 10(9)/L (P = .02). WBC levels during MTX/6MP therapy may underestimate
      the degree of MTX/6MP treatment intensity, especially in order children.
      Pharmacokinetic monitoring could be useful for optimizing MTX/6MP maintenance
      therapy.

PMID- 10897816
TI  - Successful chemotherapeutic treatment of diencephalic syndrome with continued
      tumor presence.
AB  - A 7-month-old infant with typical features of diencephalic syndrome (DES)
      associated with a hypothalamic mass, most probably a glioma, was treated with
      chemotherapy. The tumor showed clear shrinkage, but after more than 2 years
      regrowth was noted. During the treatment period the child regained normal growth
      and became free of symptoms. As radiation therapy, especially at a young age, has
      significant adverse effects and a neurosurgical approach to the diencephalic
      region also has the potential to cause significant sequelae, a chemotherapeutic
      option, when it exists, is preferred. Thus, in an infant in whom a glioma is
      suspected to be the cause of the DES, based on the clinical picture and the
      neuroimaging appearance, chemotherapy should be considered the primary
      therapeutic modality. Even if its effect is temporary, its use is well justified.
      The most appropriate treatment protocol still needs to be determined.

PMID- 10897817
TI  - Human herpesvirus-6 (HHV-6)-associated hemophagocytic syndrome.
AB  - Virus-associated hemophagocytic syndrome (VAHS) is characterized by histiocytic
      proliferation and phagocytosis triggered by virus infections. Viruses in the
      herpes group, especially the Epstein-Barr virus (EBV), are well known to cause
      VAHS; however, the relationship between this syndrome and human herpesvirus-6
      (HHV-6) infection has rarely been reported. In this study, we describe a 23-month
      old girl who exhibited typical manifestations of VAHS associated with HHV-6
      infection. To the best of our knowledge, this case is the fifth reported case in
      the English literature.

PMID- 10897818
TI  - Involvement of chromosomes 1 and 17 in a case of neuroblastoma.
AB  - We report here the cytogenetic analysis of a neuroblastoma from a 6-month-old
      male. Both conventional GTG banded analysis and fluorescence in situ
      hybridization were performed. The tumour was found to have a
      der(17)t(1;17)(p34;q21).

PMID- 10897819
TI  - Dysembryoplastic neuroepithelial tumor: a curable cause of seizures.
AB  - Dysembryoplastic neuroepithelial tumor (DNT) was first characterized in 1988 by
      Daumas-Duport and Scheithauer [1], who described 39 cases in children with
      morphologically distinct brain tumors. Partial complex seizures (PCSs), well
      defined neuroimages, and typical pathologic findings were characteristic.
      Surgical resection of the tumor was usually curative. We present a new case of a
      child with PCSs who was diagnosed and treated for DNT. The clinical presentation
      and the difficulties of the differential diagnosis are discussed.

PMID- 10897820
TI  - Hodgkin's disease in association with Down syndrome: a case report.
AB  - The increased incidence of malignancies, especially acute leukemia, in Down
      syndrome has been clearly established. The association of Hodgkin's disease with
      Down syndrome has not been extensively documented, and only a few cases have been
      reported. We present here a case report of Hodgkin's disease in an 11-year-old
      female child with Down syndrome. The child presented with a stage IVB nodular
      sclerotic Hodgkin's disease and died of progressive disease. We also present a
      brief review of the mechanisms of development of malignancy in Down syndrome.

PMID- 10897821
TI  - Is there a rationale for the prophylactic prescription of hematopoietic colony
      stimulating factor after a bacteriologically documented neutropenic infection?

PMID- 10897822
TI  - [Bronchial laser: techniques, indications, and results].
AB  - Laser emits a light characterised by being monochromatic, phased and collimated.
      Since the beginning of the '80s the fibers ND-YAG laser, whose energy may be
      transmitted by quartz fibres, is the type principally used for therapeutic
      bronchoscopy. It may be used to coagulate or to vaporize endoluminal lesions. The
      effect looked for depends on the level of density of power selected. During rigid
      bronchoscopy, YAG laser is usually applied in the coagulation mode, with a weak
      liberation of energy. Further resection is then achieved mechanically with the
      rigid tube or forceps. For malignant lesions the laser has a palliative action in
      eliminating endoluminal tumour mass. Its use has overturned the management of
      progressive tracheal or bronchial asphyxia. Outside emergencies, its action can
      be combined with radio and chemotherapy. For benign lesions its action may be
      curative. The laser is however poorly adapted for extrinsic compression and for
      infiltrating lesions where other more appropriate endoscopic methods should be
      used.

PMID- 10897823
TI  - [Endobronchial brachytherapy].
AB  - Endobronchial brachytherapy was developed following the miniaturization of radio
      active sources enabling the use of fiberoptic techniques to deliver treatment at
      high dose yet substantially reducing the duration of treatment. Endobronchial
      brachytherapy has been used in patients presenting with symptomatic obstruction
      of the proximal bronchial tree in association with laser therapy. The level of
      responses in these palliative indications is around 80 per cent. Currently, other
      investigations are undergoing evaluation to test the method in association with
      conventional treatment to determine whether brachytherapy can augment local
      control. In the treatment of small tumours when other conventional treatments are
      not possible brachytherapy employed alone has shown undoubted efficacy. However
      there remain numerous problems to resolve: what is the ideal protocol in terms of
      total dose, dose per fraction, the order of dosing and fractions? How can
      secondary complications to endoluminal irradiation be limited in particular for
      curative therapy. An answer should be found for all these questions before this
      technique is eventually integrated into the primary treatment regimes for
      bronchial cancer.

PMID- 10897824
TI  - [Endobronchial brachytherapy: techniques and indications].
AB  - Endobronchial cryotherapy has seen significant developments in France,
      particularly since 1984. It is a method of relieving obstruction based on the
      cytotoxicity of low temperatures. Flexible or rigid probes are used with nitrous
      oxide. Immediate cytotoxicity is doubled up with a delayed but intense vascular
      effect explaining the haemostatic efficacy of this technique. Tumour destruction
      is invariable without risk of perforation but necrosis is delayed occurring
      within 10 or 15 days. The technique is not adaptable to emergency situations but
      acts perfectly well on very cellular or vascular tumours. Its indications are
      complementary to laser assisted resection and enable the treatment of
      infiltrating lesions, local implantation or early neoplasms. Theoretically the
      histological and vascular effects should potentiate the effects of radiotherapy
      and chemotherapy. Randomised protocols are underway to establish the clinical
      relevance of this.

PMID- 10897825
TI  - [High-frequency thermocoagulation. Use in bronchial endoscopy].
AB  - High frequency thermocoagulation is a relatively recent technique of destroying
      tracheobronchial tumour mass. It selects the thermal effect of electrical current
      whilst avoiding the electrolytic and faradic effects of nerve and muscle
      stimulation. With gentle coagulation which is generally utilised the tissues are
      heated to between 70 and 100 degrees with the formation of water vapour and
      immediate destruction of the tissues. The electrodes are usually unipolar and are
      either rigid or flexible. The HF current which circulates across the tissues is
      gathered and evacuated by neutral electrodes. A new generation of fiberoptic
      bronchoscopes which isolate the exit current may optimise the safety of the
      procedure. New generators delivering a stable voltage controlled by a
      microprocessor enable the control of the process of coagulation and adapt the
      thermal energy delivered to the volume and nature of the tissue to be destroyed.
      The electrode is put in contact with the tissues. The immediate effects is
      similar to those described with laser. The simplicity, speed of utilization,
      minimal morbidity and relatively low cost has made this an interesting technique
      even in developed countries where the investment budgets are becoming more and
      more limited.

PMID- 10897826
TI  - [Phototherapy in the treatment of bronchial cancer].
AB  - Photodynamic therapy (PDT) is a new treatment modality for cancer based on the
      interaction of light and a photosensitizing agent located in the tumour,
      resulting in cell death. The mechanism of action of PDT and clinical applications
      in therapy of lung cancer are discussed. The most encouraging results have been
      obtained in patients with early stage lung cancer. Therapeutical improvement in
      this field may also result from advances in technology and use of new
      photosensitizers.

PMID- 10897827
TI  - [Silicone tracheobronchial endoprosthesis].
AB  - Silicone endoprostheses are used to replace loss of support in tracheobronchial
      cartilage. The main silicone stents are similar to those of the Montgomery T
      tube, the Westaby, Dumon and Cooper-Hood prostheses. The major indications are
      malignant tumours and benign stenosis after anastomotic resection or graft. All
      have in common a degree of narrowing greater than 50%. An initial bronchoscopy
      enables a precise assessment of the zone to support. The prostheses are then put
      in place using a rigid bronchoscope. An annual bronchoscopic review is
      recommended associated with clinical supervision. Their removal is simple even
      after being in position for a long period. A multicentre study (Marseille, Saint
      Etienne, Brescia and Barcelona) report their experience of 1574 prostheses
      positioned in 1058 patients. The localisation was tracheal (54%), left main
      bronchus (21%), right main bronchus (18%). The average time in place was 1.2
      years for benign tumours(maximum 6.2 years) and four months for malignant tumours
      (maximum 4.7 years). Complications were rare and included migrations (9.5%),
      granulomas (7.9%) and obstructions (3.6%). Thanks to their being well tolerated,
      their simplicity in handling, silicone prostheses are currently an essential
      choice to re-establish patency of the airways in patients presenting with benign
      or malignant tracheobronchial pathology.

PMID- 10897828
TI  - [Expandable stents and composite prosthesis].
AB  - Today, numerous expandable and mixed silicone metallic stents for trachea and
      bronchi are available. Among the many technical propositions, Nitinol is a new
      alloy with promising potential, offering the advantage of shape memory. The right
      stent is the one which best meets the needs of the individual stenotic situation
      as evaluated by endoscopy and CT. Sufficient experience has been acquired only
      with the Dumon stent, giving exact information about its qualities and possible
      complications. The new stents are thinner. Some can be inserted under
      fluoroscopic and fibroscopic control. They are presumed to produce fewer
      complications an provide answers to some still unresolved questions such as
      dyskinesia or stenosis on short bronchi. They appear to be more easily inserted
      on the tracheo-bronchial tree. More experience is needed to satisfactorily
      identify specific indications and contraindications. A prospective registry will
      be important to obtain comparative information more quickly.

PMID- 10897829
TI  - [Prosthesis: indications, contraindications and follow-up].
AB  - The use of stents or endoprostheses to treat tracheobronchial obstruction is
      firmly established. The most important indication for stent placement are
      inoperable stenoses of the central airways, whose main component is extrinsic
      compression due to malignant, less frequently to benign disease. In experienced
      hands the short- and long-term results are excellent. When considering stent
      placement the functional benefit for the patient should be highly likely. With
      respect to this, the parameters to be assessed before and in regular intervals
      after stent placement include a physical examination, a chest roentgenogram or a
      CT scan, pulmonary function tests, bronchoscopy, and quality of life. Of all the
      various stents on the market the cylindrical silicone stent designed by Dumon is
      the one most widely used and represents the standard against which all other
      models have to compete. Expandable metal stents have advantages over most
      silicone stents through their thin walls and their excellent adaptability to
      greatly varying airway diameters. The current development of covered expandable
      stents should make it possible to combine the good biocompatibility known of
      silicone stents with the excellent flexibility and favorable wall to inner
      diameter ratio of the metal stents. This development will make expandable stents
      much more versatile for the treatment of malignant and benign obstructions of the
      central airways. Effective sealing of fistulas in airways without a concomitant
      obstructive component is another most welcome indication for this type of stents.
      The future might well belong to hybrid stents with metallic components and a
      smooth synthetic covering of silicone or polyurethane. The ongoing research in
      stents shows that the "ideal stent" for all purposes does not exist and probably
      never will. Quite often the specific stent type needed can only be determined
      during therapeutic endoscopy. Every specialist practicing in the area of stenting
      should therefore have an armamentarium of a few different types available and use
      the one best indicated in a specific situation.

PMID- 10897830
TI  - [Indications of bronchial endoscopy in suspected tracheo-bronchial foreign body
      in children].
AB  - The diagnosis and early extraction of a respiratory foreign body (FB) in a child
      requires a rapid bronchoscopy. Thus, the possibility of a foreign body requires
      an endoscopy even in the absence of clinical or radiological signs. While the
      sensitivity of "the foreign body syndrome" is important (79-85%) its specificity
      is low (21-46%) which results in numerous endoscopies which do not show FB. This
      justifies the promotion of flexible fibroscopy, under a simple local anaesthesia
      of the upper airways and some sedation, each time that the foreign body is not
      obvious. That is when there is an absence of a radio-opaque foreign body (2-20%
      of cases) or an absence of associated unilateral diminution in breath sounds or
      ipsilateral obstructive emphysema (a positive predicted value of 94%, 95%
      confidence interval: 71-100%). The complications of flexible fibroscopy are rare
      but still justify its performance in an environment where there is resuscitation
      equipment and the possibility of rapidly performing a rigid bronchoscopy. Rigid
      bronchoscopy, which requires a general anaesthesia, remains the best technique to
      remove a foreign body in a child. It is also indicated initially in cases of
      respiratory distress where there is a fear of a foreign body in the trachea. The
      extraction of the CE by flexible fibroscopy under general anaesthesia has been
      reported in children but it is more difficult and more risky.

PMID- 10897831
TI  - [Anesthesia in interventional bronchoscopy].
AB  - Interventional rigid bronchoscopy requires the same careful anesthetic management
      as any type of surgery. Furthermore, access to airways for both endoscopist and
      anaesthetist raises difficult problems. Hypoventilation with its consequences is
      a major risk, especially for patients with impaired ventilatory capacity. General
      anesthesia warrants controlled or assisted mechanical ventilation, without
      precise spirometric monitoring because of air leakage. Discussion of indications
      between both operators is needed. Careful preoperative evaluation is required.
      Ultra short intravenous anesthetic agents are chosen for a rapid recovery of
      consciousness and ventilation. Ventilation is generally manually assisted or
      delivered by high frequency jet ventilation. Flexible fiberoptic bronchoscopy is
      systematically performed before extubation. Interventional rigid bronchoscopy is
      ideally performed in an operating room or an adjacent area or in an intensive
      care unit in case of complication. Postoperative supervising in a recovery room
      is mandatory.

PMID- 10897832
TI  - [Post-intubation tracheal stenosis].
AB  - Post intubation tracheal stenosis (STPI) is a rare but serious complication of
      tracheal intubation and/or tracheotomy. The epidemiology has changed over the
      last twenty years. The diagnosis is sometimes difficult to establish on clinical
      grounds alone. Flexible bronchoscopy is often necessary to confirm the diagnosis
      and to influence treatment. The ideal curative treatment is surgical resection of
      the stenosis with end-to-end tracheal anastomosis. In patients presenting with
      definitive or transitory contraindications to this treatment there is a place for
      interventional endoscopy. Rigid bronchoscopy enables mechanical dilatation of the
      STPI which can be associated with Nd-Yag laser ortracheal endoprostheses. In
      certain cases interventional bronchoscopy may be curative. However in all cases
      the management of such lesions remains multi-disciplinary involving
      pulmonologists, thoracic surgeons, otolaryngologists and anaesthetists.

PMID- 10897833
TI  - [Complications of interventional bronchoscopy].
AB  - Interventional bronchoscopy associates different techniques; rigid bronchoscopy
      under general anaesthesia, the utilisation of the laser, cryotherapy,
      electrocoagulation and the positioning of endobronchial prostheses. It it used
      most often in those patients whose respiratory reserve is precarious. It is
      important to recognise the potential complications of these different techniques
      in order to prevent them as far as possible. This article also reviews the
      principal complications which are linked to each technique which has previously
      been described.

PMID- 10897834
TI  - [Therapeutic endoscopy. Synthesis].

PMID- 10897835
TI  - [Interventional medical thoracoscopy].
AB  - Interventional thoracoscopy is an important tool for diagnosis of pleural
      disease. We present a description of available material and thoracoscopic
      methods, discussing therapeutic informations for: pleural effusion, pneumothorax,
      sympathectomy, empyema. Instruction for each therapeutic situation are presented
      together with expected results.

PMID- 10897836
TI  - [Surgical video-thoracoscopy].
AB  - Surgical video thoracoscopy represents a new surgical approach to thoracic
      disease. Its objective is to limit thoracotomy trauma to the pleural wall and at
      the same time to eliminate the consequences of post-thoracotomy pain and post
      operative respiratory dysfunction. There are certain indications which are
      already accepted as the gold standard, others still require validation and the
      inverse that certain interventions will probably be excluded from the domain of
      video thoracoscopy with acquired experience. The best indications are: the
      treatment of spontaneous pneumothorax in a young person, lung biopsy, the
      excision of peripheral parenchymal nodules of uncertain aetiology, the diagnostic
      approach to mediastinal adenopathy notably nodes which are inferiorly situated
      and inaccessible to mediastinoscopy or anterior mediastinotomy, the debridement
      of purulent pleurisy and/or haemothorax, the initial exploration before
      thoracotomy of a pulmonary tumour accompanied by a pleural effusion which may be
      minimal or irregularities of the parietal pleura, a thoracic sympathectomy,
      pleural symphysis for pleural tumour pathology, the pleuropericardial
      fenestration in cases of double pathology, pleural and pericardial requiring both
      a diagnostic approach and symphysis.

PMID- 10897837
TI  - [Bronchial and pulmonary vaso-occlusions].
AB  - The technique of vaso-occlusion (or embolisation) consists in occluding one or
      several vessels which are causing haemoptysis. Either of the pulmonary
      circulations (systemic bronchial or pulmonary) may be the cause and sometimes
      both are. In systemic pulmonary hypervascularization the pathological issues are
      affected by high pressure vascularisation at the expense of functional
      vascularisation and are the source of frequent episodes of bleeding. Bronchial
      and systemic vaso-occlusion has proven efficacy and safety on condition that
      strict rules are respected to avoid complications; the detection of potentially
      dangerous arteries (spinal, coronary and visceral) and a choice of material for
      embolisation which is adapted to the therapeutic strategy and the clinical and
      angiographic presentation. The indications for the procedure are dictated by
      severe or recurrent haemoptysis. Vaso-occlusion of pulmonary arteries which is a
      rarer indication dominated by conditions such as arteriovenous malformation
      (MAVP). The technique is adapted to the number, to the size and to the diffusion
      of MAVP which is characterised precisely by computed tomography. Vaso-occlusion
      is the treatment of first choice for MAVP only leaving failures of vaso-occlusion
      to surgery and certain pedicular forms have a very short afferent of large
      calibre.

PMID- 10897839
TI  - [In Process Citation]

PMID- 10897838
TI  - [Percutaneous treatment of superior vena cava obstruction].
AB  - Endovascular therapies represent the most efficient treatment of benign or
      malignant obstructions of the superior vena cava. The indication of stenting in
      case of malignant obstruction depends on the severity of the superior vena cava
      syndrome, the histological type of the tumor, and the response to radiotherapy
      and chemotherapy. Restoration of the superior vena cava patency is obtained in
      more than 90% of cases, with persistent good mid and long term results.
      Complications are rare, especially after early treatment. Stenting of benign
      obstructions, especially in patients who undergo hemodialysis, allows to restore
      venous accesses. However, indication of treatment may be discussed because the
      initial and late patencies are lower than in malignant obstructions.

PMID- 10897840
TI  - [Exposure to asbestos. Role of thoracic imagery in screening and follow-up].
AB  - Chest radiograph and computed tomography are the most appropriate imaging tools
      for detecting asbestos-related pleural and parenchymal disease due to their
      availability and performances. The cost and irradiation delivery of conventional
      chest X-rays are limited. Technical parameters and reading should be
      standardized. Digital chest radiograph will progressively replace conventional
      techniques but technical standards and performance data are lacking. Computed
      tomography, using spiral or conventional mode, explores the whole lung and
      pleura. High resolution computed tomography samples both lung and pleura but its
      sensitivity for parenchymal fibrosis detection is greater. Several methods can be
      employed and should be recommended to reduce radiation dose in spiral and high
      resolution computed tomography. Computed tomography is more sensitive and
      specific than chest radiograph in early detection of pleural plaques and
      parenchymal fibrosis but is not infallible. The error reading rate of chest
      radiograph for early detection of bronchial carcinoma is high. Computed
      tomography is more sensitive but lacks specificity and leads to detect a high
      rate of lesions the relation to asbestos exposure of which are difficult to
      establish. No scientific data are available to assess the contribution of imaging
      in early detection of mesothelioma.

PMID- 10897841
TI  - [Exposure to asbestos: role of respiratory function tests as tools for screening
      and follow-up].
AB  - Among pulmonary function tests, spirometries and flow-volume curves are used in
      occupational or environmental field. They require the compromise between simple
      and sufficiently performance to be useful. Limitation factors explain the low
      sensitivity and the absence of specificity related to asbestos (tobacco...). The
      wide interindividual variation compared to standards limits meaning for early
      detection. A significant epidemiological difference makes no sense for individual
      detection. The carbon monoxide diffusing capacity, even classical, has restricted
      uses. Unlike diffuse pleural thickening, the worst cases with circumscribed
      pleural plaques lead to limited lung capacity decline. If not, they are
      associated to pulmonary abnormalities or tobacco. The early asbestos-related
      parenchyma diseases are associated to restrictive ventilator disorders, small
      airway obstruction or isolated single breath carbon monoxide diffusing
      limitation, leading to great difficulties for specific early detection criteria
      validation. Comparative pulmonary changes over time greater than the
      physiological pulmonary slope should be a good alert indicator.

PMID- 10897842
TI  - [Measurement of asbestos fibers in the air: description and limitations of the
      measuring techniques used].
AB  - Since the beginning of this century a wide range of methods were used to evaluate
      the asbestos exposure of workers. Instruments such as the konimeter, thermal
      precipitator, impinger or tyndallometer were employed to collect dust samples.
      Currently, the membrane filter method associated with phase contrast optical
      microscopy is widely accepted. These different sampling methods are presented in
      this paper and the relationships between asbestos concentration recorded by means
      of methods used in the past and with the current membrane filter method or with
      direct-reading instruments are discussed. Emphasis is put on the difficulty to
      use such relationships which were often established for specific situations (in
      the mine industry for instance). For non occupational exposure the use of
      electron microscopy methods is evaluated.

PMID- 10897843
TI  - [Role of biometric analysis in the retrospective assessment of exposure to
      asbestos].
AB  - Despite intrinsic limitations due to differences in the bio-persistence of the
      various asbestos types, in the definition of control populations and in
      analytical techniques used by the laboratories, mineralogical analysis of
      biological samples is useful in the assessment of past exposure to asbestos. It
      provides additional information to occupational and environmental questionnaires,
      particularly when exposure to asbestos is doubtful, unknown or forgotten by a
      subject. Results should be interpreted taking into account clinical information.
      A positive result does not mean existence of asbestos-related disease. A negative
      result does not exclude previous significant asbestos exposure, clearly
      identified by an occupational questionnaire (particularly for exposure to
      chrysotile). Threshold values indicative of a high probability of previous
      asbestos exposure have been established for bronchoalveolar lavage fluid (BALF)
      samples and lung tissue samples. Quantification of asbestos bodies by light
      microscopy is easy to perform. Sensitivity and specificity of this analysis
      towards the total pulmonary asbestos fiber burden is good. Therefore this
      analysis should be performed first. Mineralogical analysis in BALF or lung tissue
      should be considered only when sampling is supported by diagnostic or therapeutic
      implications.

PMID- 10897844
TI  - [Biological markers and exposure to asbestos].
AB  - Review of published studies clearly demonstrates the absence of value of the CEA,
      CYFRA21-1 and NSE biomarkers, either alone or combined, for the screening of lung
      cancer. So far, diagnostic value of other biomarkers, such as p53 tumor
      suppressor gene or the detection of antibodies raised against receptors encoded
      by oncogene or against p21 protein (encoded by K-ras oncogne) remains
      speculative. This justifies that efforts should be reinforced in this field.
      Similarly, further studies are needed for biomarkers indicative of individual
      susceptibility to asbestos-related cancers, particularly in the field of P450
      cytochromes or glutathione-S-transferase.

PMID- 10897845
TI  - [Anatomopathological tools for screening and medical surveillance of people
      exposed to asbestos].
AB  - The deleterious effects of asbestos exposure include benign and malignant pleuro
      pulmonary lesions leading to considerable morbidity and mortality, underlying the
      necessity for improvement of early detection strategies. Pathological techniques
      (morphology and immunohistochemistry) remain the gold standard for diagnosis of
      asbestos related disorders, together with mineralogic studies and for
      determination of associated pathological processes. There are yet no reliable
      pathological tools able to survey and detect asbestos exposed patients which are
      non invasive, acceptable for the patients and obvious in directing efficient
      therapy. Three main conclusions are drawn: 1) Promising approach includes EMA
      immunostaining in the evaluation of suspicious mesothelial lesions; 2) P53,
      proteases immunostaining and K-Ras mutation analysis in early detection of
      bronchial preneoplasia; 3) sputum screening for specific tumor markers of
      transformation (hRNPA2/B1), or morphometric DNA quantification for the detection
      of subclinical bronchopulmonary carcinomas. These recent developments are the
      first step of a long road to routine detection of these lesions.

PMID- 10897846
TI  - [Endoscopic diagnosis of mesothelioma].
AB  - Mesothelioma is a rare disease but its incidence is rising. Diagnosis is still
      difficult but has been improved by immunohistochemical techniques and panels of
      pathologists. At the present time thoracoscopy is the most sensitive method for
      diagnosis of mesothelioma and a good alternative to thoracotomy. The main
      indication for thoracoscopy is unexplained pleurisy that cannot be diagnosed by
      needle biopsy. Thoracoscopy allows diagnosis in 95% of cases. Pleural ultrasound
      can be useful for diagnosis of limited pleurisy without multiple radiation
      exposure. Thoracoscopy is usually performed under light general anesthesia using
      a rigid endoscopic system. If possible, pneumothorax should be induced the day
      before the procedure to allow better assessment of the entry route and prevent
      adherences or symphysis. Tolerance of thoracoscopy is excellent. Thoracoscopy
      allows not only complete visualization of the pleural cavity including the
      diaphragmatic visceral pleura and the lung but also multiple biopsies. In early
      stage disease, thoracoscopy permits distinction of patients with stage Ia
      (involvement confined either the parietal or diaphragmatic pleura and purely
      inflammatory aspect in 50% of cases) from patients with stage Ib (involvement of
      the visceral pleura). Median survival is 28.3 months for stage Ia versus 10
      months for stage Ib. Endoscopic observation enables accurate staging of tumor
      involvement which is an important prognostic finding and is an essential
      technique for early diagnosis of mesothelioma.

PMID- 10897847
TI  - [Role of endobronchial endoscopic techniques in the detection of bronchial
      cancer].
AB  - The fiberoptic endoscopy remains the only technique available for the diagnosis
      of roentgenographically occult bronchial carcinomas. In this indication, its use
      is restricted to the exploration of the proximal part of the bronchial tree, and
      practically, to early detection of squamous cell carcinomas. To date, the cost
      and invasiveness of the endoscopic techniques imply that they cannot be used as a
      mass screening tool. However, prospective early lung cancer detection programs
      using fiberoptic endoscopy in a very high risk, selected population could be
      designed. Several research programs are currently conducted around the world to
      evaluate this strategy. The preliminary results of a prospective study conducted
      in Rouen University Hospital suggest that the use of new technologies such as
      fluorescence endoscopy in such programs might be useful to detect very early
      bronchial lesions, especially in smokers with heavy occupational exposure to
      asbestos. To date, the application of such programs to large populations is
      limited by the low availability and high cost of the fluorescence endoscopy
      technique. More precise knowledge on risk factors associated with early proximal
      lung cancer lesions and a strict evaluation of the risk/benefit ratio of the
      endoscopy strategy are also needed.

PMID- 10897848
TI  - [Risk assessment of benign asbestosis (dose-effect relationship, time-effect
      relationship, co-factors)].
AB  - Despite the lack of precision of asbestos exposure assessments and the
      limitations of the main diagnostic epidemiological tool for asbestos-related
      diseases (i.e. standard X ray films), several issues concerning the risk of
      development of asbestos-related diseases are well established. For asbestosis,
      now a rare disease, the existence of a positive dose-response relationship, with
      a threshold or no-effect level, has been clearly demonstrated. The slope of the
      relationship curve is steeper for amphiboles than for chysotile, as it is for
      increased fiber length. Asbestosis is associated with an increased risk of
      bronchial carcinoma, however it is now known that exposure to asbestos of itself
      increases the risk of cancer even in the absence of any radiographic signs of
      pulmonary fibrosis. Pleural plaques occur even when the level of asbestos
      exposure is low. They are not only dose-dependent but are also latency-related.
      They have no prognostic significance in asbestos-exposed workers, but are
      associated with an increased risk for the subsequent development of mesothelioma
      and bronchial carcinoma when compared to the risk of the general population.
      Diffuse pleural thickening is associated with higher levels of asbestos exposure
      than those associated with pleural plaques. It usually follows a benign pleural
      effusion, which is a less frequent but earlier consequence of asbestos exposure
      than the other asbestos-related diseases documented above.

PMID- 10897849
TI  - [Asbestos and risk of cancer: exposure-effect relationships for occupationally
      exposed populations].
AB  - For high levels of exposure (> 1 f/ml), the risk of lung cancer increases
      linearly with the cumulative exposure, and is the same for all types of asbestos;
      the risk of mesothelioma increases linearly with the level of exposure, is time
      dependent and higher for amphiboles. The effects of asbestos and smoking for lung
      cancer are independent, and the probability that a cancer is due to asbestos is
      the same among smokers and non-smokers. There is no scientific method for
      quantifying directly the risks associated to low levels of exposure (< 1 f/ml).
      The only possible approach is to extrapolate from the risks observed at high
      levels to low levels. Proportionality without threshold between dose and risk is
      not certain, but is the most plausible model. Using this model, one can expect
      about 30 additional cases of cancer for 10,000 men exposed at the level of 0.1
      f/ml from 20 to 65 years, and about 16 additional cases for 10,000 women. These
      are high figures compared to other health hazards.

PMID- 10897850
TI  - [Medical impact of screening of benign pleural lesions associated with the
      inhalation of asbestos dust].
AB  - Asbestos-related benign pleural lesions can involve the parietal pleura (pleural
      plaques), and/or visceral pleura as focal or diffuse (diffuse pleural thickening)
      fibrosis. Benign asbestos pleurisy and rounded atelectasis are linked with
      visceral pachypleuritis, the former as a cause, the latter as a consequence. The
      prevalence of these lesions, particularly pleural plaques, is very high, reaching
      25% in populations of workers exposed intermittently to asbestos. Conventional
      radiology has a sensitivity less than 50% for detection of plaques, and a
      specificity less than 85%. Tomodensitometry is today the reference diagnostic
      tool: availability, cost and irradiation have to be considered before its use in
      mass screening. Pleural plaques are most often asymptomatic and a functional
      impairment cannot be proven usually on an individual basis. Visceral pleural
      thickening is more often accompanied by symptoms (dyspnea, pain) and functional
      impairment. There is no treatment susceptible to produce a regression of pleural
      lesions. Asbestos exposure increases the risk of pulmonary and pleural cancers.
      However there is no evidence of an increased risk in subjects with plaques
      compared with subjects without plaques but an equivalent asbestos exposure. The
      cost and the risk of diagnostic procedures induced by the screening, as well as
      the anxiety provoked by the detection of radiologic abnormalities are to be
      considered. Finally it is difficult today to justify the screening of benign
      pleural lesions by arguing an improvement of the life expectancy or of the
      quality of life of former asbestos exposed workers. It is probable that benefit
      of a screening will be of a social type, at an individual or a collective level.

PMID- 10897851
TI  - [Asbestosis].
AB  - Asbestosis is a rare pneumoconiosis secondary to inhalation of asbestos fibers.
      It follows sufficient professional exposures (more than 25 fibers x years/ml).
      The mean latency is 20 years. Clinical symptoms include exertion dyspnea,
      crackles and clubbing. Chest radiography the performances of which have been
      enhanced by the use of the ILO score shows fine reticular or reticulonodular
      opacities which predominate in pulmonary bases often in association with benign
      pleural abnormalities. An ILO score equal or higher than 1/1 is suggestive of
      asbestosis in the context of a compatible professional history. Pulmonary
      function is typical of diffuse interstitial lung disease. High resolution CT is
      the most performance investigation in particular in presence of asbestosis either
      minimal or of recent origin. The diagnosis of asbestosis is based on the
      professional exposure, a compatible interstitial lung and pleural disease and the
      exclusion of alternative hypothesis. The diagnosis can be comforted by
      bronchoalveolar lavage (cytology and biometeorology). Various evolutions are
      possible: stability, progression to respiratory insufficiency, increased
      incidence of bronchial carcinoma. Life expectancy is reduced in severe cases.
      There is no efficient medical treatment. Asbestosis is recognized as a
      professional disease. A better recognition of asbestosis necessitates a
      performance policy of depistage in populations with significant present or past
      exposure and an appropriate diagnostic strategy including high-resolution-CT.

PMID- 10897852
TI  - [Medical impact of screening of broncho-pulmonary cancer in subjects exposed to
      asbestos].
AB  - Most of available data about screening for lung cancer concern smokers. These
      studies concluded that no benefit can be expected from sputum cytology. Moreover
      with radiologic screening, early stages and resectability are more frequent and
      survival of screened patients is longer. Yet lung cancer specific mortality is
      not influenced. Various explanations are presented. For asbestos workers, lung
      cancers can occur even without asbestosis. So screening, if any should be applied
      to any exposed patient with or without radiologic abnormalities. Experts assert
      that medical data are not conclusive to demonstrate the benefit or the absence of
      benefit of radiological screening. If a screening program is planned, asbestos
      workers alone could be included on the condition that such strategy is evaluated.
      Prospective studies about new procedures, especially Chest-CT, are also
      advisable.

PMID- 10897853
TI  - [Malignant mesothelioma: clinical and therapeutic study].
AB  - Like lung cancer, mesothelioma is difficult to diagnose early. Nevertheless
      disease stage is the determinant factor for outcome of treatment. Effective
      diagnostic examinations must be undertaken promptly. Thoracoscopy is one of the
      best diagnostic procedures provided that it is skillfully performed to prevent
      complications such as development of subcutaneous nodules along the pathway of
      the trocar. Several arguments have been proposed against routine screening
      including low incidence of the disease, poor sensitivity and specificity of
      screening techniques, and lack of effective therapy documented by phase III
      study. However there are a number of arguments in favor of screening. The high
      risk population is well defined. Although no control study is currently
      available, promising new results have been observed in limited forms, i.e., 62%
      response rate at stage IA with 39% survival at 5 years in patients presenting
      epithelial forms without lymph node involvement treated by pleuro-pneumonectomy,
      chemotherapy, and radiotherapy. Screening is necessary to recruit more early
      stage patients for further clinical trials to improve therapeutic techniques.
      Poor outcome of treatment could be due to delayed diagnosis. Early diagnosis is
      also needed to allow compensation of occupational disease to begin while the
      patient is still alive.

PMID- 10897854
TI  - [Social impact of screening and of medical surveillance on people exposed to
      asbestos].
AB  - A medical screening program has collective and individual impact. The collective
      benefit of medical screening for people exposed to asbestos would be financial
      (better compensation of occupational diseases related to asbestos). The cost of
      compensation would be attributed to the special assurance fund for occupational
      diseases. A medical screening of asbestos diseases would set an example for other
      Public health problems. It would be important for admission of social damage for
      the French nation. For individuals, social benefits would be better (compensation
      during work stop and annuities). But screening can have a negative psychological
      impact for asymptomatic persons. Persons exposed to asbestos and patients with
      asbestos diseases are able to quit their job for anticipated retirement. Is it a
      benefit for patients with mesothelioma or lung cancer? It is a very important
      benefit for asbestosis. The risk is to change the objective of medical screening
      into a social screening. The financial and medical benefits of screening for
      hyaline plaques is very poor. Awarding social damage is important for
      individuals.

PMID- 10897855
TI  - [Prevention programs for people exposed to asbestos: results of the ongoing
      activities].
AB  - Programs of prevention concerning the populations exposed or having been exposed
      to asbestos include on the one hand, specific programs of medical surveillance
      and on the other hand, interventions of primary prevention. The latter were
      essentially anti-smoking campaigns and chemo-prevention trials of lung cancer
      through taking of vitamin A derivatives. In the first part of this review, the
      results of the experiments of the medical follow, up organized in France and
      abroad will be shown. These studies allow particularly to appraise both the usual
      latency of appearance of lung pathologies due to asbestos and the contribution of
      thoracic scanography in their diagnosis. The interest of the new techniques, such
      as the autofluorescence fiberscopy, is tackled too. The studies on primary
      prevention, detailed in the second part, underline the necessity to stop of
      tobacco consumption among the smokers exposed to asbestos. Moreover, this study
      concludes that the chemo-prevention of lung cancer through vitamin A derivatives
      is not yet effective. Some general principles which may be useful to the setting
      up programs of prevention are put forward in conclusion.

PMID- 10897856
TI  - [Screening of diseases associated with asbestos. On-going activities, synthesis].
AB  - Medical screening requires always assessment. On the basis of ongoing studies on
      occupational health asbestos programs, we suggest some recommendations for
      asbestos screening after occupational exposure. The proposal for asbestos workers
      post-exposure surveillance should take into account the medical but also the
      social aspects of the problem. Post-exposure screening of asbestos workers
      includes an evaluation of occupational exposure, compulsory basis medical check
      up, the characteristics of the radiological investigations and schedule of the
      medical surveillance. In conclusion, we suggest some general recommendations for
      asbestos screening after occupational exposure, particularly the necessity to
      obtain a concerted approach of asbestos screening with regional and national
      networks, the concern of their assessment and the implementation of specific
      research studies.

PMID- 10897857
TI  - [Strategy of clinical medical surveillance of people exposed to asbestos].

PMID- 10897858
TI  - Heart rate and respiratory frequency in hydrostatically compressed, liquid
      breathing mice.
AB  - The effects of hydraulic compression on heart rate and respiratory frequency were
      studied in liquid-breathing, hypothermic (17-31 degrees C) mice. Increasing the
      hydrostatic pressure caused a bradycardia that was first evident at 25 at. and
      progressed to 48% of the control heart rate at 175 at. The bradycardia was
      reversed, although incompletely, by decompression. Similar changes in respiratory
      frequency were seen. Autonomic blockage with atropine and propranolol did not
      change the response patterns to any major extent. Compression rate (2-6 at. x min
      1) did not seem to influence the degree of heart-rate reduction. Compression
      caused an increase in colonic temperature, and decompression a decrease (0.5
      degree C for a pressure change of 100 at.). These temperature changes could be
      ascribed partly to adiabatic heating and cooling of the body tissues as revealed
      by similar changes in dead animals and partly to increased metabolic heat
      generation in connection with compression-induced convulsions. The temperature
      changes, although partly accounting for the hysteresis in the heart-rate changes
      during compression/decompression, were not responsible for the major effects. It
      was concluded that high pressure causes bradycardia by a direct action on cardiac
      pacemaker cells.

PMID- 10897859
TI  - Decompression-induced bubble formation in salmonids: comparison to gas bubble
      disease.
AB  - The relationship of gas bubble disease (GBD) in fish to decompression-induced
      bubble formation was investigated with salmonids. Acute bioassays were used to
      determine equilibration times for critical effects in fish decompressed from
      depths to 200 fsw. It was found that equilibration of critical tissues was
      complete in 60-90 min. Salmonids and air-breathers are sensitive to
      decompressions at similar levels of supersaturation if elimination of excess gas
      following decompression is unrestricted. However, if elimination is restricted,
      bubble formation and growth increase accordingly. Tests with mixtures of He-O2,
      Ar-O2, N2-O2 (80% inert gas: 20% O2) and pure oxygen demonstrated that gas
      solubility as well as supersaturation (delta P), pressure ratio (initial
      pressure: final pressure), and absolute pressure must be considered in setting
      tolerance limits for any decompression. Gases with higher solubility are more
      likely to produce bubbles upon decompression. Oxygen, however, does not follow
      this relationship until higher pressures are reached, probably owing to its
      function in metabolism and in binding with hemoglobin. Tissue responses observed
      in both GBD and decompressed fish involved similar pathological effects at acute
      exposures. The circulatory system was consistently affected by bubbles that
      occluded vessels and blocked flow through the heart.

PMID- 10897860
TI  - Assessment of vertical excursions and open-sea psychological performance at
      depths to 250 fsw.
AB  - A series of 10 two-man descending vertical excursion dives was carried out in the
      open sea from an ocean-floor habitat off the coast of Puerto Rico by four
      aquanauts saturated on a normoxic-nitrogen breathing mixture at a depth of 106
      fsw. The purpose of these dives was two-fold: to validate laboratory findings
      with respect to decompression schedules and to determine whether such excursions
      would produce evidence of adaptation to nitrogen narcosis. For the latter, tests
      designed to measure time estimation, short-term memory, and auditory vigilance
      were used. The validation of experimental excursion tables was carried out
      without incidence of decompression sickness. Although no signs of nitrogen
      narcosis were noted during testing, all subjects made significantly longer time
      estimates in the habitat and during the excursions than on the surface.
      Variability and incomplete data prevented a statistical analysis of the short
      term memory results, and the auditory vigilance proved unusable in the water.

PMID- 10897861
TI  - Left-ventricular performance in man during breath-holding and simulated diving.
AB  - We measured left-ventricular (LV) systolic time intervals (STI) to determine
      whether breath-holding and simulated diving evoke a depression of LV performance
      in man similar to that previously demonstrated in natural divers. Records of STI
      were obtained by a noninvasive procedure in 15 adult males who had breath-holding
      diving experience during supine rest, at 30 and 60 s of simple breath-holding
      (BH) and at 30 and 60 s of BH combined with cold, wet facial stimulation (FS).
      Changes in both BP and HR during FS reflected cardiovascular behavior typical of
      simulated diving. The isovolumic contraction period increased 13% and 31% after
      60 s of BH and FS, respectively. LV ejection time shortened by 30 ms during BH
      and by 37 ms during FS. These measurements of STI represent the first description
      of cardiac cycle components during the human diving response. The alterations in
      STI suggest that a reduction in LV performance, as seen by a decreased rate of
      preejection pressure development and a diminished stroke volume, had occurred
      during the apneic maneuvers. In addition, there was a trend in these measures
      indicating that FS potentiated the response over that which occurred during BH.
      Thus, it appears that man exhibits a depression of LV performance during
      simulated diving similar to that found in natural divers.

PMID- 10897862
TI  - Skeletal response of growing rats to continuous long-term hyperbaric helium
      oxygen exposure.
AB  - Bone growth and composition were studied in growing rats following continuous
      long-term hyperbaric exposure. Six groups of eight rats each were maintained at
      21 ATA He-O2 (200 mm Hg O2) and six groups were kept in simulated test chambers
      under room-air conditions. One group each of pressurized and control animals were
      removed and analyzed after 2, 3, 5, 8, 10, and 12 weeks. Each animal was weighed
      and sacrificed. One femur was removed for fresh, dry, ash, and matrix weight
      measurement and determination of calcium and phosphorus content. The pressurized
      animals showed a significant reduction in body-weight gain after each exposure
      period. Femurs from pressurized animals weighed less than controls but had
      significantly greater femur/body weight percentages. Calcium and phosphorus
      content was normal and the ratio of matrix to mineral was unchanged. Results
      suggest that pressurized animals had accelerated metabolic rates and inadequate
      caloric intake. However, measurements of bone mineral and matrix content indicate
      the skeleton develops normally under hyperbaric conditions.

PMID- 10897863
TI  - Brain stimulation in rats exposed to hyperbaric environments.
AB  - Six rats were trained to make an operant response to receive brief trains of
      electrical current to the lateral hypothalamus (self-stimulation). All animals
      were then randomly exposed to pressures of 4.03, 5.51, 7.06, or 10.1 ATA
      breathing either compressed air or N2-O2 and 13.1 ATA (N2-O2 only). When the
      subjects breathed air at pressures of 7.06 and 10.1 ATA, rate of self-stimulation
      decreased by 32 and 43%, respectively. No differences were observed in rate of
      response at any pressure when the animals breathed N2-O2 with the partial
      pressure of oxygen maintained at 0.2 ATA. When an oxygen-nitrogen mixture was
      breathed at 3 ATA in which the PO2 was similar to compressed air at 10.1 ATA,
      self-stimulation rate was decreased by 40%; this suggests that PO2 is a critical
      variable influencing behavior mediated by brain stimulation. Results are
      discussed in terms of the use of self-stimulation as one tool for better
      understanding the neuronal mechanisms of behavior as they relate to breathing-gas
      mixtures at increased pressures.

PMID- 10897864
TI  - The effects of body position and a vasodilator on xenon133 elimination from human
      subcutaneous fat.
AB  - The elimination of Xe133 from a deposit in the subcutaneous adipose tissue
      adjacent to the anterior tibial muscle was recorded by an external scintillation
      detector in 16 human subjects in sitting and in supine body position in a neutral
      environmental temperature (28 degrees C). The xenon clearance rate was increased
      in supine compared to sitting body position by a mean of 33%. I also studied the
      effect of a sympathomimetic beta 2-receptor stimulating agent using the same
      technique in 16 supine subjects. A perorally administered ester of terbutaline
      increased the xenon-elimination rate by a mean of 103%. The increased xenon
      elimination rates in the supine body position and after the drug administration
      may reflect corresponding increases in adipose-tissue blood flow. The findings
      are in accordance with earlier measurements of an increase in central and
      peripheral blood flow and an increased whole-body, nitrogen-elimination rate
      during supine body position. The results might be of importance in decompression
      routines and in the treatment of decompression sickness.

PMID- 10897865
TI  - Decompression sickness during saturation dives.
AB  - Available Navy saturation diving data were analyzed for an evaluation of the
      therapeutic adequacy of decompression sickness treatment procedures and for
      delineation of precipitant factors in the etiology and treatment of decompression
      sickness during saturation dives. None of the cases of decompression sickness
      recorded during saturation dives involved more than musculoskeletal or joint
      pain, and in 96% of the cases the joint pain was confined to the diver's knees.
      In 89% of the cases symptoms appeared while the divers were still under pressure.
      The subsequent recompression treatment of these cases resulted in full relief in
      only 35% of the cases; the remaining 65% completed the therapy and subsequent
      decompression with residual pain which diminished over a period of weeks. The
      adequacy of the recompression appears to be inversely proportional to the depth
      of reported onset of symptoms and the time required to obtain even partial relief
      is directly related to the magnitude of the recompression ratio used. Four
      explanations are suggested for the limited recompression therapy common in
      saturation diving: increase in musculoskeletal pain with recompression, peer
      pressure to avoid extension of the chamber confinement, lack of severe
      neurological symptoms, and the tremendous depths required to obtain a reasonable
      recompression ratio. The author further suggests that future treatment procedures
      will require a departure from the accepted concept of radically decreasing the
      volume of inert gas bubbles by increasing pressure.

PMID- 10897866
TI  - Automatic compensation by capillary gauge for altitude decompression.
AB  - According to simple theory, the indications of a capillary depth gauge are such
      that ascent rate and decompression-stop position are correct to give unaltered
      gammas (tissue overpressures) and a safe dive profile--independent of the density
      of the medium or of surface altitude--if position indications are used directly
      in a standard decompression table. The usual dial depth gauges must be doubly
      corrected for altitude but not medium before tables can be used, while distance
      measuring systems should be corrected for both altitude and medium. The capillary
      gauge dive profile is theoretically conservative when timed step decompression
      rather than continuous ascent is used if gamma increases with altitude.

PMID- 10897867
TI  - The direction of apparent movement during transient pressure vertigo.
AB  - Pressure vertigo or alternobaric vertigo is the type of vertigo normally
      associated with relative overpressure in the middle ear. As with other types of
      vertigo, it should occur only if there is unequal stimulation of the left and
      right vestibular systems: there should be a lawful relation between the
      orientation of the head, the side of the overpressured ear, and the direction of
      apparent movement. Few published accounts give information on all these aspects.
      This paper reports some old and new cases which suggests that, when the head is
      upright during the ascent, overpressure in the right ear causes apparent bodily
      and visual movement to the right (clockwise), while overpressure in the left ear
      has the opposite effect. Horizontal orientation of the head probably reduces the
      vertigo. There are no detailed and unequivocal reports of pressure vertigo during
      descent, or with the head inverted. Some reports exist of tumbling sensations and
      of tilting of the visual scene, but the exact circumstances are unclear.

PMID- 10897868
TI  - [Endogenous interaction of neurotransmitters and aging: studies on the basal
      ganglia of awake rats].
AB  - The interaction of glutamate and dopamine in the basal ganglia of the awake rat
      during the normal process of aging is revised. Using a novel approach, that of
      blocking the reuptake of glutamate, the effects of increasing concentrations of
      endogenous glutamate on the extracellular concentrations of dopamine in striatum
      and nucleus accumbens in the young rat were investigated. It was found that
      increasing concentrations of glutamate correlated significantly with increasing
      concentrations of dopamine in striatum and nucleus accumbens. Moreover the
      increase of dopamine in both structures was significantly reduced after blockade
      of NMDA and AMPA/kainate glutamate receptors, suggesting that the increase of
      dopamine was mediated by glutamate. The interaction glutamate/dopamine expressed
      by its ratio showed a significant age-related decrease in nucleus accumbens but
      not in neostriatum, so that to a given amount of glutamate less increase of
      dopamine is produced. It is suggested that the interaction glutamate-dopamine
      represents a balanced input to the GABA neuron in the basal ganglia and that
      during aging this balance is disrupted. It is speculated on the significance of
      this glutamate-dopamine disruption in relation to the changes in motor behavior
      found with age.

PMID- 10897869
TI  - [Gregorio Maranon and Walter B. Cannon].
AB  - The story of a friendly relationship between two great scientists, Gregorio
      Maranon (G.M.) and Walter B. Cannon (W.B.C.), is reported. Both share a common
      interest for the biology of emotion. In the early twenties they had already made
      important contributions to the nature of the emotional processes. The meeting
      point was in the interpretation of the somato-visceral response elicited by the
      injection of adrenaline in humans (G.M.) and of the emergency reaction (W.B.C.).
      The relevant moment in their relationship was the utilization by W.B.C. of the
      G.M.'s results concerning the artificial induction of the visceral changes
      typical of strong emotions as the main argument against the James-Lange theory of
      emotion, as no specific emotion was generated by the adrenaline; instead, only
      "as if" subjective feelings were reported by patients. A clear distinction then
      was drawn by G.M. between perception of the vegetative changes and the physical
      emotion proper. Since then it was clearly defined the cognitive component as
      essential and primary as concerns to the nature of emotion. The visceral changes
      are not determinant of the emotional quality. Its role was restricted to the
      strength and duration of the emotional experience.

PMID- 10897870
TI  - [Conservative surgery in ovarian cancer].
AB  - Surgery for ovarian cancer is always radical. In young patients with wish of
      pregnancy and in early stages, the conservative surgery can be contemplated. This
      type of surgery involves removing the tumoral ovary, leaving the healthy ovary
      and uterus. In these cases, the age, stage, histologic type, grade and biological
      factors must be considered. There is controversy about the surgical approach:
      laparoscopy or laparotomy, the indication to perform biopsy of the contralateral
      ovary and pelvic-paraaortic lymphadenectomy. In high-risk cases adjuvant
      chemotherapy must be considered. We present our experience in 330 common
      epithelial and germinal ovarian carcinomas. We performed conservative surgery in
      13. Four patients got pregnant and 3 of them delivered a term newborn. In 13 of
      52 borderline tumors a conservative surgery was performed and 3 term deliveries
      were obtained. All patients are alive and free of disease.

PMID- 10897871
TI  - [Gastroesophageal reflux and Helicobacter pylori].
AB  - The relationship between Helicobacter pylori (H. pylori) infection and
      gastroesophageal reflux disease (GERD) is not well known yet, and has some
      controversial issues. There is indirect epidemiological evident, not yet proven,
      that H. pylori may have a protective role against GERD. Hypochlorhydria caused by
      gastritis located mainly at corpus would be the principal physiopathological
      protector mechanism against GERD. Even knowing that more studies are needed, the
      risk of developing GERD after the H. pylori eradication seems to be increased in
      some groups of patients. In the presence of the microorganism, the efficacy of
      acid suppression therapy may decrease, and its long-term use could favour the
      progression to corpus atrophic gastritis. Specialized intestinal metaplasia in an
      endoscopically normal-appearing cardia may precede adenocarcinoma, and its
      prevention would vary, depending on its controversial origin, secondary to
      carditis, H. pylori or GERD.

PMID- 10897872
TI  - [Catecholaminergic secretions and monovalent cations in adrenal medulla].
AB  - Taken together the results of this work indicate that 1st) The countertransport
      systems, [Na+]i-[Ca2+]o or [Li+]i-[Ca2+]o are implicated on the catecholamine
      secretory response evoked by ouabaine and lithium in the cat adrenal medulla.
      2nd) Both procedures (ouabain, or lithium) induce an increment of cytosolic
      [Ca2+]i, secundary to the accumulation of monavalents cations (Na+ or Li+) in the
      cytosol, which is finally responsible for the catecholamine secretory response
      and 3rd) In addition to [Na+]i-[Ca2+]o or [Li+]i-[Ca2+]o counter transport
      systems, either Na+ or Li+ could depolarize the cell and therefore activate
      voltage-dependent Ca2+, and possibly Na+ channels leading to further increments
      of [Ca2+]i.

PMID- 10897873
TI  - [Coffee and health].
AB  - The authors analyse the use of coffee in the modern society. They inform about
      its consumption in the different environments and more precisely in the
      university community.

PMID- 10897874
TI  - [Physical activity, bone remodeling, and osteoporosis].
AB  - Scientific publications have produced debate about the action of the physical
      activity in the osteoporosis. It's condition by several factors, like the
      repercussion of the physical activity in the bone remodeling, the loss of bone
      mass with immobilization or the gravitational effect. The progressive knowledge
      of the different nutritional and direct and indirect biochemical factors that
      stimulates, inhibits or modulates the bone remodeling, and the new methodology in
      the evaluation of the bone mineral density and the biomarkers of bone resorption
      or bone formation have confirmed or denied the results apparently contradictory.
      We analyse the advantages of the action of the physical activity in the normal
      bone remodeling process, his risk factors in some deportive actions. The not
      confirmation of the therapeutic utility of the physical activity in the
      osteoporosis, and the actual research about the amount of bone that can be gained
      by activity or high bone mass in a determined age, with special emphasis in the
      activity for tension of muscular contraction and the percussion effect for the
      specific sport action.

PMID- 10897875
TI  - Laboratory reports of human viral and selected non-viral agents in Canada--1994
      and 1995.

PMID- 10897876
TI  - Children first. An interview with David Gray Ross.

PMID- 10897877
TI  - The basics of child support enforcement.

PMID- 10897878
TI  - Welfare reform: a state perspective.

PMID- 10897879
TI  - Recent trends and variations in nonmarital childbearing.

PMID- 10897880
TI  - Charting a new approach: the Government Performance and Results Act of 1993.

PMID- 10897881
TI  - Communicating our message. An interview with Ann Garcelon.

PMID- 10897882
TI  - CSE resources on the "net".

PMID- 10897883
TI  - Bringing in fathers.

PMID- 10897885
TI  - Resolving problems through mediation.

PMID- 10897884
TI  - Hospital based paternity establishment in Colorado.

PMID- 10897886
TI  - Partnering with law enforcement.

PMID- 10897887
TI  - A call for reform: the U.S. Commission's report.

PMID- 10897888
TI  - An international perspective: child care in South Africa.

PMID- 10897889
TI  - An outbreak of group C rotavirus gastroenteritis among children attending a day
      care centre in Belem, Brazil.
AB  - In August 1993, an outbreak of group C rotavirus-associated gastroenteritis
      occurred among children attending a day-care centre in Belem, Brazil. Of the 64
      children, 21 (33%) became ill. Group C rotavirus was identified in faecal
      specimens from 8 (38%) children with diarrhoea by electron microscopy (EM) and an
      enzyme immunoassay (EIA), using antibodies specific to the Cowden strain of
      porcine group C rotavirus. By polyacrylamide gel electrophoresis (PAGE), a
      pattern similar to that of group C rotavirus was observed in 5 (62.5%) of the 8
      EM- and EIA-positive samples. These 5 faecal samples were confirmed to be
      positive for group C rotavirus by reverse transcriptase-polymerase chain
      reaction, using specific VP6 and VP7 primers. This is the first report of an
      outbreak of diarrhoea in North Brazil associated with group C rotavirus. These
      findings suggest that group C rotavirus may be an important aetiological agent of
      diarrhoea in this region, which requires further study.

PMID- 10897890
TI  - Characterization of virulence factors of Aeromonas isolated from children with
      and without diarrhoea in Tripoli, Libya.
AB  - During September 1992-August 1993, stool samples from 157 children with diarrhoea
      and 157 matched healthy controls were examined for the presence of Aeromonas and
      other enteropathogens. Aeromonas strains were tested for haemolytic activity,
      haemagglutination patterns, and antibiotic susceptibility. In total, 62 Aeromonas
      were isolated, of which 27 (17.2%) were from children with diarrhoea and 35
      (22.3%) from healthy controls. Only 23 (14.6%) of the diarrhoeal children and 28
      (17.8%) of the healthy controls were positive for Aeromonas; of which, 4 (2.5%)
      of the diarrhoeal children and 6 (3.8%) of the healthy controls showed multiple
      species. Aeromonas hydrophila was isolated from 5 (3.2%) children with diarrhoea
      and from 9 (6.4%) controls, A. veronii bv sobria from 8 (5.1%) and 7 (4.5%), A.
      caviae from 13 (8.3%) and 17 (10.8%), and A. schubertii from 1 (0.6%) and 2
      (1.3%) respectively. No significant difference in the haemolytic activity of
      Aeromonas was found between diarrhoeal and healthy children. However, a
      significant difference (p < 0.002) was observed in mannose-resistant
      haemagglutination (MRHA) by diarrhoeal isolates of Aeromonas (7/27, 26%) compared
      to the healthy controls (1/35, 3%). Aeromonas strains were uniformly sensitive to
      ciprofloxacin, gentamicin, and nalidixic acid. The results of this study suggest
      that A. caviae strains may be associated with diarrhoea in children and MRHA may
      be used as one of the virulence markers for distinguishing between Aeromonas
      isolated from diarrhoeal children and healthy controls or environmental isolates.

PMID- 10897891
TI  - Detection of group- and subgroup-specific antigens of bovine rotaviruses in
      Bangladesh.
AB  - The study was carried out to detect group- and subgroup-specific antigens of
      bovine rotaviruses. Stool specimens, collected from diarrhoeic calves of the
      Savar Dairy Farm, Bangladesh, were examined by an enzyme-linked immunosorbent
      assay, using group- and subgroup-specific monoclonal antibodies. Thirty-three
      specimens showed specificity for group A rotavirus. While subgrouping, 21 group A
      positive specimens showed subgroup I specificity. Twelve specimens did not react
      with either of the subgroup I- and subgroup II-specific monoclonal antibodies.

PMID- 10897893
TI  - WHO-ORS in treatment of shigellosis.

PMID- 10897892
TI  - Enteropathogenicity and antimicrobial susceptibility of new Escherichia spp.
AB  - To determine the mechanism of enteropathogenicity of the newly described
      Escherichia species, a total of 50 clinical isolates of Escherichia spp. from
      diarrhoeal stools were studied. Twelve isolates (24%) were found to be E.
      vulneris, 6 (12%) E. fergusonii, 2 (4%) E. hermannii, and the rest 30 (60%) were
      E. coli. Most isolates of the new species were resistant to ampicillin,
      tetracycline, and co-trimoxazole, but were susceptible to cephalosporins and
      aminoglycosides. The representative strains of all the new species produced
      significant fluid accumulation in the rat ileal loops both by live cells and
      their culture filtrates. E. vulneris, isolated from stools, showed maximum fluid
      accumulation. Thus, it can be inferred that these species are diarrhoeagenic, but
      their roles on extra-intestinal infections remain to be determined.

PMID- 10897894
TI  - Virulence factors in Aeromonas veronii bv veronii.

PMID- 10897895
TI  - Bibliography on diarrhoeal diseases.

PMID- 10897896
TI  - [Psychotherapy on the internet. Without inhibitions in the world wide web].

PMID- 10897897
TI  - [Spelling aids for physicians. A million words correct].

PMID- 10897898
TI  - [Sport as antidepressant?].

PMID- 10897899
TI  - [Chronic hepatitis and cholangitis. The liver at risk].

PMID- 10897900
TI  - [End of the Di Bella cancer therapy].

PMID- 10897901
TI  - [Typhus abdominalis in travelers. Headaches originating in the abdomen].
AB  - The incidence of typhoid fever in emerging countries remains high, being
      estimated to be 500 per 100,000 head of population. Tourists from the
      industrialized countries can contract the infection in particular when travelling
      under conditions of poor hygiene in endemic regions. The risk of contracting
      typhoid appears to be highest on lengthy travels on the Indian subcontinent,
      while short visits to Latin America or Africa appreciably less often result in an
      infection. Currently, two vaccines are approved for use in Germany: a live oral
      vaccine containing the defective S. typhi mutant Ty 21a, and a parenteral
      inactivated vaccine prepared from the Vi capsid antigen of S. typhi. Both
      vaccines are well tolerated and provide similar levels of protection. The
      reported protection rate for the live vaccine varies in various studies between
      33 and 67%; that of the inactivated vaccine between 55 and 75%. Medical advice
      prior to travel should weigh up such risk factors as age, duration of the
      journey, destination and the nature of the journey. While vaccination is
      particularly recommended for travelers with one or more risk factors, it should
      always be pointed out that an infection is nevertheless possible. In view of the
      fact that immunization against hepatitis A and typhoid fever are often indicated
      simultaneously, the development of a combination vaccine would be desirable.

PMID- 10897902
TI  - [Enteritis without diarrhea--a case from general practice. Fever, bradycardia and
      leukopenia lead to the diagnosis].

PMID- 10897903
TI  - [Health education as "safety belt" for the patient. How travel medicine fits into
      general practice].

PMID- 10897904
TI  - [Hemorrhagic erythema. Morphologic and descriptively oriented diagnosis (4)].

PMID- 10897905
TI  - [Cutaneous lupus erythematosus: when does it become systemic?].

PMID- 10897906
TI  - [Exanthemas in childhood].

PMID- 10897908
TI  - [Varicose veins: how to fit compression stockings exactly].

PMID- 10897907
TI  - [Atopic eczema and nutrition].

PMID- 10897909
TI  - [Lyme borreliosis--vaccines in the "pipeline"].

PMID- 10897910
TI  - [Lasers in dermatology--what they can really accomplish].

PMID- 10897911
TI  - [Eating disorders in adolescence: warning signs].

PMID- 10897912
TI  - [Cardiovascular function and anemia. Using caution in patients with established
      cardiac diseases].

PMID- 10897913
TI  - [Saw palmetto fruit extract for treatment of benign prostatic hyperplasia.
      Results of a placebo-controlled double-blind study].

PMID- 10897914
TI  - [Heart failure. 2: Chronic heart failure].

PMID- 10897915
TI  - [Abdominal pain and renal failure after alcoholic intoxication. Intraperitoneal
      urinary bladder rupture after alcohol excess].

PMID- 10897916
TI  - [If reform fails, so will the administration. Interview by Peter Jentsch].

PMID- 10897918
TI  - [Cortisone pulse therapy in dermatology: controlled use promises high rate of
      success].

PMID- 10897917
TI  - [High dosage corticosteroids: in multiple sclerosis pulse therapy is of value].

PMID- 10897919
TI  - [Polyposis nasi: systemic cortisone therapy is suited for prevention or
      pretreatment before surgery].

PMID- 10897921
TI  - [Telemedicine in diabetology: online kids consult the physician much more
      readily].

PMID- 10897920
TI  - [Corticoid research: in non-genomic effects there are still some questions].

PMID- 10897922
TI  - [Sexual dysfunctions in the man and woman. "Oysters before making love"].

PMID- 10897923
TI  - [After introduction of the potency pill. The coming-out of impotent patients].

PMID- 10897924
TI  - [Pain treatment at negative 110 degrees C?].

PMID- 10897925
TI  - [Cancer management and prevention. Progress in small steps].

PMID- 10897927
TI  - [Senile dementia--a diagnostic error from the clinic. Thinking of hypothyroidism
      in the elderly].

PMID- 10897926
TI  - [Medicine in the nursing home--problem analysis and goals. What is essential in
      general practice management].
AB  - Nursing homes are important, but often neglected, facilities for the care of
      frail older people. The demand for nursing home capacity in Germany will continue
      to increase over the next decade despite improvements in infrastructure of home
      care and day care centers. The leading medical reason for this is the growing
      number of elderly persons suffering from neurodegenerative diseases, depression,
      and stroke. Currently, more than 650,000 residents are in various forms of
      institutionalized care in Germany. To date, the medical profession has shown
      little interest in establishing an efficient medical care system for such
      patients, nor are care-providing physicians required to undergo special training
      in Germany. The article describes current practice and future principles of
      geriatric treatment.

PMID- 10897928
TI  - [Patient management in the nursing home: are you fit for patient management?
      Considerations for the practice team].

PMID- 10897929
TI  - [Cement removal in changing hip prosthesis implants. Search for a conservative
      method].

PMID- 10897930
TI  - [Vasculitis with good prognosis. Schoenlein-Henoch purpura in adulthood].

PMID- 10897931
TI  - [Fully automated injection pen for prevention of thrombosis. Tolerance,
      convenience and patient compliance].

PMID- 10897932
TI  - [Polymorphic photodermatitis. 1: Disease picture and clinical aspects].

PMID- 10897933
TI  - [The confusing thyroid gland. Factitious hyperthyroidism].

PMID- 10897934
TI  - [Health care reform: resistance grows. Global budget resistant to reform?].

PMID- 10897935
TI  - [The woman physician and burnout. Do women physicians have more stress?].

PMID- 10897936
TI  - [Gentle abortion with the pill?].

PMID- 10897937
TI  - [With current findings on the wrong path. Retrospective review discloses proper
      diagnosis].

PMID- 10897938
TI  - [Coronary emergency--the best pathway for rapid diagnosis].
AB  - Acute coronary syndrome includes instable angina pectoris, non-Q-wave infarction
      and, in current publications, usually also Q-wave infarction. The common
      pathological substrate is intracoronary plaque rupture with the formation of a
      thrombus. A careful work-up of the symptoms and their classification permits a
      presumptive diagnosis. This must then be confirmed by ECG without delay. On the
      basis of the clinical picture and the ECG, an acute myocardial infarction can be
      diagnosed unequivocally, and treatment initiated immediately. In these cases,
      laboratory findings merely confirm the diagnosis, and provide information on the
      size of the infarction and the success of reperfusion. In the event of an unclear
      ECG, rapid troponin tests may help to establish the diagnosis and monitoring of
      treatment, as well as providing prognostic information. While, formerly, a strict
      differentiation was made between instable angina pectoris, non-transmural and
      transmural infarctions, current pathophysiological knowledge makes the
      overarching term of acute coronary syndrome appear to be a more suitable term.

PMID- 10897939
TI  - [Current therapeutic strategies in acute coronary syndrome. New and established
      drug and interventional therapy].
AB  - Therapeutic options in acute coronary syndrome (unstable angina pectoris/non-Q
      wave myocardial infarction), as also in acute Q-wave infarction, include
      conservative medical and mechanical-interventional measures. Early
      hospitalization for surveillance and induction of treatment is always necessary.
      Administration of oxygen, analgesia, sedation and treatment with nitrates, beta
      blockers or calcium antagonists, acetylsalicylic acid (ASA) and heparin are the
      basic measures. As alternatives to ASA, the new ADP antagonists, ticlopidine,
      clopidogrel, and as an alternative to heparin, hirudin or low-molecular-weight
      heparins can be used. If this does not result in rapid clinical stabilisation
      (here, transient ST-T changes in the ECG and the detection of troponine I or T
      represent major risk indicators) the new glycoprotein-IIb/IIIa receptor
      antagonists may be employed as highly potent platelet aggregation inhibitors. In
      addition, the patients should then undergo coronary angiography prior to
      interventional treatment of the underlying coronary stenosis.

PMID- 10897940
TI  - [Angina at rest as an alarm syndrome. Progress in treatment of acute coronary
      syndrome].

PMID- 10897941
TI  - [Position of the German Hypertension League on diuretic therapy. Risk of cancer
      is minor compared with the benefit of lowering blood pressure].

PMID- 10897942
TI  - [Ambulatory long-term blood pressure determination improves therapy of
      hypertension].

PMID- 10897943
TI  - [Acute perianal venous thrombosis. 2. Surgical therapy in general practice].

PMID- 10897944
TI  - [Unilateral sclerosis of the femur. Paget disease].

PMID- 10897945
TI  - [Physicians may not aid asylum seekers. Interview by Werner Loosen].

PMID- 10897946
TI  - [Before your patients lose control. Pruritus: stopping the pattern].

PMID- 10897947
TI  - [Complementary medicine, III: Homeopathy--well represented on the internet].

PMID- 10897948
TI  - [Adverse drug effects: 10,000 preventable fatalities per year?. Interview by Dr.
      Stephanie Czajka].

PMID- 10897949
TI  - [A pill for smoking cessation. Prospects for success are doubled].

PMID- 10897950
TI  - [Treated cervix carcinoma: what is changed during sex?].

PMID- 10897951
TI  - [Polyposis nasi--effective treatment without operation? Broad etiological
      spectrum, individual therapy].
AB  - Various factors are thought to be involved in the etiology and pathogenesis of
      nasal polyps. The clinical symptoms include nasal obstruction, hyposmia or
      anosmia and recurrent sinusitis. At the cellular level eosinophilic granulocytes
      appear to have an important role to play, the growth, differentiation and
      degranulation of which is apparently controlled by interleukin 5. In the present
      study, practically relevant aspects of the pathophysiology, diagnosis, treatment
      and diagnostic differentiation of the various types of polyps are discussed, with
      the latter point also being examined for its importance with regard to
      therapeutic consequences.

PMID- 10897952
TI  - [Foetor e naso: the nose strikes the alarm. From rhinitis, ozena and foreign
      bodies].

PMID- 10897953
TI  - [Nasal obstruction, anosmia, hypernasal speech--key symptoms for nasal polyps.
      Focal points for the general practice team].

PMID- 10897954
TI  - [When parents decide against therapy for the children. The case of Emil M.: a
      conflict between parents and medicine].
AB  - If parents refuse to allow an accepted, scientifically well-founded treatment for
      their child, and if this results in obvious negative consequences for the child's
      welfare, the physician can appeal to the family court. Before doing so, however,
      a detailed explanation of the situation and counseling of the parents is
      imperative. In an emergency that brooks no delay, however, the physician can
      carried out the treatment he considers absolutely necessary even against the
      wishes of the child's parents. If, as a result of unacceptable parental decisions
      -e.g. withdrawal of treatment from the child--harm to the child ensues, the
      parents can hardly be pursued by the law, since, according to the principles of
      criminal law, this would only be possible if it can be proved without a shadow of
      doubt that the treatment would definitely have prolonged the child's life, or
      with certainty protected it from some other prejudice.

PMID- 10897955
TI  - [Rapid treatment of scabies with a single ivermectin administration. Routine
      topical treatment takes several days].

PMID- 10897956
TI  - [Diarrhea and gastrointestinal hemorrhage. Etiology: hereditary metabolic
      disease].

PMID- 10897957
TI  - [Prevention of thrombosis in genetic susceptibility? Thrombosis ABC: APC
      resistance].

PMID- 10897958
TI  - [Hyperhidrosis. 3: Iontophoresis in treatment of hyperhidrosis plantaris].

PMID- 10897959
TI  - [Unilateral Raynaud phenomenon. Subclavian steal syndrome in total occlusion of
      the left subclavian artery].

PMID- 10897961
TI  - [Dr. Wolfgang Holz, NAV, on laboratory reform. KBV has set costs much too low.
      Interview by Wolfgang Loosen].

PMID- 10897960
TI  - [Promoting general practice management. Health insurance wants still mor power].

PMID- 10897962
TI  - ["Intolerant" combination partners? Nitrates are still not fully utilized].

PMID- 10897963
TI  - [Younger hypertensive patients. High normal RR values are too much!].

PMID- 10897964
TI  - [Oral fluoroquinolones. Rational antibiosis as needed].

PMID- 10897965
TI  - [Drinking tips for patients with urinary calculi. Apple cider instead of beer].

PMID- 10897966
TI  - [Proper eating and drinking. Fewer colics and reduced costs].

PMID- 10897967
TI  - [Laser surgery for myopia. Are eyeglasses superfluous?. Interview by Dr.
      Christina Berndt].

PMID- 10897968
TI  - [Resistance tests to improve therapy. More specific use of AIDS drugs].

PMID- 10897969
TI  - [Infants and young children with fever of unknown origin. Systematic procedure
      based on a diagnosis-therapy diagram].
AB  - Febrile children comprise a substantial proportion of ambulatory pediatric
      visits. The management of febrile children needs to be structured to minimize the
      likelihood of unfavorable outcomes as well as the unnecessary use of antibiotics.
      The guidelines for the management of febrile children in this review are based on
      recently published data and are aimed to be recommendations until bacterial foci
      and pathogens are identified.

PMID- 10897970
TI  - [Measles. A viral illness with risk of permanent damage].
AB  - Measles is a highly contagious exanthematous disease. After an incubation period
      of almost two weeks, catarrhal prodromic, associated with initial attacks of
      fever appear. Typical manifestations are Koplik's spots. The exanthema appears
      together with the second rise in temperature. The illness confers lifelong
      immunity. In individual cases, an encephalitis resulting in permanent
      neurological deficits must be expected. Every effort should be made to prevent
      this condition from arising. To this end, immunization with a combination
      measles, mumps, rubella (MMR) vaccine is recommended.

PMID- 10897971
TI  - [Which lipid parameters are atherogenic? Pathological lipid values and their
      therapeutic consequences].
AB  - In cross-sectional investigations, disturbances in lipid metabolism are found in
      about 40-50% of the population. A particularly close correlation is found between
      cardiovascular mortality and elevated LDL cholesterol. But disordered
      triglyceride metabolism and increased concentrations of lipoprotein(a) are also
      considered major factors that further the atherosclerosis process. A knowledge of
      the underlying mechanisms and the possibilities for influencing lipid metabolic
      disorders provide the basis for rational treatment. Unfortunately, disorders in
      lipid metabolism often continue to go undetected until the so-called endpoints
      (infarction, stroke) have occurred.

PMID- 10897972
TI  - [Therapy of androgenetic alopecia with finasteride. What must be considered in
      consultation and drug prescribing].
AB  - Androgenetic alopecia in men is genetically determined, but occurs only when the
      testosterone metabolite dihydrotestosterone (DHT) is present in normal levels.
      The drug, finasteride, inhibits the enzyme 5-alpha-reductase II, which is
      responsible for converting testosterone to DHT. One 1 mg tablet (Propecia) of
      finasteride daily lowers serum DHT levels by about 70%, and increases serum
      testosterone by 10%. The efficacy of finasteride 1 mg has been demonstrated in a
      randomized, double-blind, placebo-controlled clinical trial involving more than
      1,500 men in whom a significant increase in hair density over a specified area of
      the scalp, and a significant improvement in appearance was noted. Following one
      year to treatment 48%, and following 2 years 66%, of the finasteride patients
      (placebo group 7% after both treatment periods) presented with visibly thicker
      hair growth. Side effects such as decreased libido, ejaculation disorders and
      erectile dysfunction were seen in fewer than 2% of the men in both the
      finasteride and placebo groups.

PMID- 10897973
TI  - [Antithrombin III deficiency: when substitute, when heparin? Thrombosis ABC, 3:
      The role of antithrombin III].

PMID- 10897974
TI  - [Basic therapy of rheumatoid arthritis. 2: Selection, long-term and combination
      therapy].

PMID- 10897975
TI  - [Increased liver values and heart hypertrophy. Primary hemochromatosis with liver
      involvement].

PMID- 10897976
TI  - [Acetylsalicylic acid long-term therapy for the ailing heart. More damage than
      good?].

PMID- 10897977
TI  - [ACE inhibitor even prevents diabetes. Sensational HOPE Study].

PMID- 10897978
TI  - [Not a taboo. Sex in rehabilitation].

PMID- 10897979
TI  - [What do our interest groups offer on the internet?].

PMID- 10897980
TI  - [Pig instead of human--how safe?. Interview by Dr. Beate Schumacher].

PMID- 10897981
TI  - [Exposing obsessive-compulsive patients: often only 3 simple questions are
      enough. The family physician as "facilitator of self-disclosure"].
AB  - For numerous patients with obsessive-compulsive disorder, the family doctor is
      the first contact person. Many of these patients have concealed their problem for
      years. This paper summarizes the forms of the disorder and their indirect
      manifestations in the doctor's office, discusses the reasons for concealment on
      the part of the patient and/or his relatives, and describes the family doctor's
      help in three areas: aiding the "birth of revelation"; initiating pharmacotherapy
      and supporting behavior therapy-related self-help for patient and relatives;
      motivating patient and relatives to seek expert psychiatric and psychotherapeutic
      aid. In the second part of the paper, the family doctor is given model
      explanations designed as answers to common questions asked by sufferers from
      obsessive-compulsive disorder.

PMID- 10897982
TI  - [Drug treatment of obsessive-compulsive disorder. With proper drugs and some
      patience many patients can be helped].
AB  - Pharmacotherapy which, together with behavior therapy, is a major pillar in the
      treatment of obsessive-compulsive disorder (OCD), can bring about a distinct
      symptomatic improvement in 50-70% of the patients. In addition to the classical
      tricyclic antidepressant, clomipramine, a number of new selective serotonin
      reuptake inhibitors have now been approved for the treatment of OCD. In
      comparison with depression, pharmacotherapy of OCD is characterized by a long
      latency of effect of eight to twelve weeks, and by the high doses required by
      some patients. A combination of pharmacotherapy and behavior therapy is superior
      to behavior therapy alone, in particular in the case of patients with
      predominantly obsessive thoughts and additional symptoms of depression. In the
      case of aggregation with the Tourette syndrome or schizotypal personality
      disorders, the additional administration of a neuroleptic is recommended. Open
      studies and case histories have reported good results with pimozide, haloperidol,
      clozapine and risperidone.

PMID- 10897983
TI  - [Emergency house call: dyspnea in a child! Sometimes a paper cup helps].

PMID- 10897985
TI  - [Thrombosis ABC, 4: Leg and pelvic vein thrombosis. Compression stockings on the
      leg and out of bed?].

PMID- 10897984
TI  - [Ambulatory phase II cardiac rehabilitation (Cologne model). 3 year outcome after
      completion of the intervention].

PMID- 10897986
TI  - [Toxoplasmosis. 2: Therapy and prevention].

PMID- 10897987
TI  - [Hip pain in long-term steroid therapy. Septic arthritis].

PMID- 10897988
TI  - [Distressing shoulder pain. Puncture and irrigation of calcium deposits in the
      joint?].

PMID- 10897989
TI  - [Prescription for treatment only a budgetary waste. Without physical therapy, the
      shoulder can easily become stiff].

PMID- 10897990
TI  - [New anticonvulsants under evaluation].

PMID- 10897991
TI  - [Chronically ill due to the environment. Does study involvement help?. Interview
      by Dipl.-Biochem. Petra Eiden].

PMID- 10897993
TI  - [Cotton swabs and ear cleaning. Should one do it or not?].
AB  - Cotton tips for cleaning out the auditory canal are readily available from
      drugstores and supermarkets. They supposedly represent a safe means of cleaning
      the ears and nose. It is the purpose of the present paper to show that the
      insertion into the ear or nose of foreign bodies in the form of cotton tips is
      not only absolutely unnecessary, but is also potentially dangerous.

PMID- 10897992
TI  - [All sudden hearing losses are not alike. Away from infusion therapy?].
AB  - The number of patients requiring treatment for acute functional disorders of the
      inner ear has increased over the last decades. The diagnosis sudden loss of
      hearing is made when the cause of a precipitous hearing impairment cannot be
      determined with clinical diagnostic means. In the large majority of such cases,
      the pathogenesis is unclear, with vascular, viral and autoimmune processes most
      commonly being considered. Against this background, numerous polypragmatic
      therapeutic measures are employed. In general treatment of sudden loss of hearing
      employs a combination of several drugs with perfusion-promoting or anti
      inflammatory effects. However, the efficacy of such an approach has not been
      established. The present article discusses a number of known ideas on the
      pathogenesis of this condition, together with the associated therapeutic
      strategies, and reports on the importance of nitrogen oxide (NO), which as recent
      studies appear to show, plays an important role in the physiology of the cochlea.

PMID- 10897994
TI  - [In sudden hearing loss, timing is important. Information for the practice team].

PMID- 10897995
TI  - [Diabetes therapy in advanced age. Managing specific problems].

PMID- 10897996
TI  - [Softeners in synthetic materials--are they harmful to humans? First indication
      of genotoxic effect of phthalates].
AB  - BACKGROUND: A wide range of phthalate derivatives are added to plastic materials,
      including PVC, as softeners. Although the possibility that these substances pose
      a risk to human health continues to be discussed, a definitive answer has yet to
      be found. In particular, their genotoxic potential has not so far been
      investigated in human material. METHOD: The literature is reviewed to provide an
      overview of the present state of such discussions. We carried out our own in
      vitro investigations into the genotoxicity of dibutylphthalate (DBP) and
      diisobutylphthalate (DIBP) in human mucosa with the aid of the alkaline version
      of single-cell microgel electrophoresis. RESULTS: Various effects of phthalates
      have been identified in the animal model, for example, changes in blood count,
      anti-androgenic or xenoestrogenic effects, proliferation of peroxisomes and
      progression of liver cell tumors. In humans, elevated phthalate levels following
      treatment with extracorporeal oxygenation have not been found to have any direct
      toxic effects. Initial results of our in vitro studies revealed a clear genotoxic
      potential in human oropharyngeal and nasal mucosa. CONCLUSION: Using suitable
      test methods, phthalates need further investigation for their health hazard
      potential in humans. In vitro experiments with two substances of this class
      involving human mucosa, indicate the possibility of geno-toxic effects.

PMID- 10897997
TI  - [Physical therapy in rheumatology. 1: Exercise, Massage, heat].

PMID- 10897998
TI  - [Inflammatory tumor of the large intestine. Florid ulcerous tuberculoid colitis
      of the ascending colon].

PMID- 10897999
TI  - [When the practice network is properly planned. With less work more income?.
      Interview by Werner Loosen].

PMID- 10898000
TI  - [Life and suffering 5,000 years ago. Paleopathologic findings in the "man from
      the ice"].

PMID- 10898001
TI  - [90 years of scientific publications in dental medicine].
AB  - 90 years of dental publications in Belgium are discussed in relation with the
      history of dental associations.

PMID- 10898002
TI  - [Philosophy, a mirror for science?].
AB  - The author regrets the lack of philosophical knowledge (in circles of dentistry)
      to judge the scientific base of research. The western epistemology is explained
      by referring to the models of reasoning used in both medicine and dentistry.
      Referring to the 17th century philosophers, the methodical doubt, the genesis of
      more general points of view, the problem of measurement, the set up of
      experiments and the formulation of laws are discussed. Referring to the 18th and
      19th century philosophers, the question of perception, correlation, interaction
      with the experiment and hypothesis relating to their probability are discussed.
      The 20th century philosophers are the occasion to discuss the influence of
      experimental models on data, the problem of the operation of this information, of
      the scientific terminology and of variability of theories, data and methods. The
      author claims a formation in scientifical philosophy for postgraduate students
      and is also emphasizing that students in the basic education level should be able
      to deal with scientific literature in a critical way.

PMID- 10898003
TI  - [Intellectual hoaxes. Various observations on epistemology and the human
      sciences].
AB  - In 1996, a New York physicist, Alan Sokal, published an article entitled
      "Transgressing the boundaries: towards transformative hermeneutics of quantum
      gravity" in the journal of cultural studies Social Text. He later revealed that
      it was a hoax; In this paper, I discuss the two main issues raised by the hoax:
      firstly, the abuse of scientific terminology by famous intellectuals such as
      Lacan, Kristeva or Irigaray, and other "postmodernist" thinkers; secondly, the
      epistemic relativism and its impact on the history and sociology of science.

PMID- 10898004
TI  - [Review and considerations apropos of the book "Science and Power" by professor
      Isabelle Stengers].
AB  - Isabelle Stengers, philosopher and chemist is professor at the "Universite Libre"
      in Brussels. This philosophical scientific essay is warning us against the abuse
      of the scientific argument for authority. Formulations such as "from a scientific
      point of view" or "objective criteria demonstrate" or "it appears from research"
      are often misused as justification for (political) decision-making and to
      shortcut a discussion.

PMID- 10898005
TI  - [From market conditions to the process of empathy. Interview of Professor M.
      Pourtois by G. Vanbelle].
AB  - G. Vanbelle, President of the Flemish Dental Association, interviews professor M.
      Pourtois of the Free University of Brussels on various topics. Are discussed the
      free market mechanisms, permanent education, quality assurance, policy of editing
      scientific articles, subvention of dental schools, evidence based medicine,
      ethics and empathy for the patient.

PMID- 10898006
TI  - [The contribution of imaging in dentistry and oral medicine].
AB  - This article discusses the new trends since 1991 in imaging modalities in
      dentistry and stomatology with special attention for computed tomography,
      ultrasonography and magnetic resonance imaging.

PMID- 10898007
TI  - [The sampling of plaque specimens in oral microbiology].
AB  - Sampling is the first and most important step in the bacterial analysis of
      periodontal or endodontal infections. Sterile paperpoints are the ultimate tool
      to perform the sampling. Sampling is preferably done under continuous CO2
      flushing, to preserve an anaerobic environment for the bacteria. For the dilution
      and the transport of the bacteria, Reduced Transport Fluid (RTF) is the most
      reliable fluid, when culturing is indicated. In all other cases, sterile
      physiologic water is sufficient.

PMID- 10898008
TI  - [Post-cure response in periodontal practice in Belgium].
AB  - The recall response of patients with prosthetic rehabilitation on implants (n =
      530) and patients treated for periodontal disease (n = 2364) in a periodontal
      private practice was evaluated. The recall response over 7 years following
      treatment showed that (1) with time the response to treatment diminished for all
      patient groups, (2) (post) juvenile periodontitis patients responded poorly to
      follow-up, (3) patients with rapidly progressing periodontitis were most eager to
      regularly visit the periodontist, (4) implant patients with complete
      rehabilitation responded better than those with partial restorations who in turn
      responded better than those with a single crown on an implant.

PMID- 10898009
TI  - [The rational use of mouthwashes].
AB  - This article discusses the currently-accepted indications of a number of
      mouthrinses and their use in the prevention of carious lesions, gingivitis and
      periodontitis.

PMID- 10898010
TI  - [Prevention of caries and osteoradionecrosis in patients irradiated in oncology.
      Critical review].
AB  - In this paper, various preventive measures regarding caries and
      osteoradionecrosis in irradiated patients with the head and neck cancer are
      discussed. Local application of high concentrations of fluoride gel as well as
      good oral hygiene are the most appropriate measures to implement.

PMID- 10898012
TI  - [74th annual meeting of the Japanese Association for Infectious Diseases.
      Fukuoka, Japan. April 20-21, 2000. Abstracts].

PMID- 10898011
TI  - [Treatment of oral epidermoid carcinoma].
AB  - The in 1994 published work in an issue of the Revue Belge de Medecine Dentaire
      devoted to oral cancer, aimed to describe and analyse the treatment modalities of
      oral cancer. Surgical treatment, radiotherapy and chemotherapy were
      systematically detailed. The esthetic and functional problems inherent to radical
      oncological surgery in the face and mouth were analysed. In most cases, surgical
      and/or prosthetic rehabilitative or reconstructive methods could limit these
      functional and esthetic inconvenient to acceptable sequelae. Dental prosthetic
      rehabilitation could with some limits benefit from dental osseointegrated
      implants: the problematic of dental implants in irradiated jaws has been claimed.
      The genuine indications of external radiotherapy and of brachytherapy were
      described and the risks so as the primordial prevention of jaw osteoradionecrosis
      were pointed out. Chemotherapy, either as palliative, adjuvant or as inductive
      treatment, had clearly shown important therapeutic limits. This presented work
      compares the actual treatment modalities of the oral cancer, pointing the main
      therapeutic acquisitions in the last 5 years and gives some optional indications
      for the future.

PMID- 10898013
TI  - [35th conference of Japanese Medical Society of Alcohol and Drug Studies.
      Yokohama, Japan. July 4-6, 2000. Abstracts].

PMID- 10898014
TI  - [The 88th annual meeting of the Japanese Urological Association. Sapporo, Japan.
      June 7-10, 2000. Abstracts].

PMID- 10898015
TI  - [The 101st Congress of the Japanese Society of Otolaryngology. Tokyo, Japan. May
      18-20, 2000. Abstracts].

PMID- 10898016
TI  - [The 43rd annual meeting of the Japanese Society of Nephrology. Nagoya, Japan.
      May 11-13, 2000. Abstracts].

PMID- 10898017
TI  - [42nd annual meeting of the Japan Geriatrics Society. Sendai, Japan. June 15-17,
      2000. Abstracts].

PMID- 10898018
TI  - [The 73rd annual meeting of the Japanese Society for Bacteriology. Sapporo,
      Japan. May 29-31, 2000. Abstracts].

PMID- 10898020
TI  - [The 44th Congress of the Japan Rheumatism Association. Yokohama, Japan. May 13
      15, 2000. Abstracts].

PMID- 10898019
TI  - [The 42nd annual meeting of the Japanese Society of Child Neurology. Osaka,
      Japan. June 8-10, 2000. Abstracts].

PMID- 10898032
TI  - Optical technologies: in search of a clinical home.

PMID- 10898033
TI  - Images of the imager: the essential role of ethics in the future of radiology.

PMID- 10898034
TI  - Discrimination of MR images of breast masses with fractal-interpolation function
      models.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the feasibility of using
      statistical fractal-dimension features to improve discrimination between benign
      and malignant breast masses at magnetic resonance (MR) imaging. MATERIALS AND
      METHODS: The study evaluated MR images of 32 malignant and 20 benign breast
      masses from archived data at the University of Pennsylvania Medical Center. The
      test set included four cases that were difficult to evaluate on the basis of
      border characteristics. All diagnoses had been confirmed at excisional biopsy.
      The fractal-dimension feature was computed as the mean of a sample space of
      fractal-dimension estimates derived from fractal interpolation function models.
      To evaluate the performance of the fractal-dimension feature, the classification
      effectiveness of five expert-observer architectural features was compared with
      that of the fractal dimension combined with four expert-observer features.
      Feature sets were evaluated with receiver operating characteristic analysis.
      Discrimination analysis used artificial neural networks and logistic regression.
      Robustness of the fractal-dimension feature was evaluated by determining changes
      in discrimination when the algorithm parameters were perturbed. RESULTS: The
      combination of fractal-dimension and expert-observer features provided a
      statistically significant improvement in discrimination over that achieved with
      expert-observer features alone. Perturbing selected parameters in the fractal
      dimension algorithm had little effect on discrimination. CONCLUSION: A
      statistical fractal-dimension feature appears to be useful in distinguishing MR
      images of benign and malignant breast masses in cases where expert radiologists
      may have difficulty. The statistical approach to estimating the fractal dimension
      appears to be more robust than other fractal measurements on data-limited medical
      images.

PMID- 10898035
TI  - CT blood pool enhancement in primates with lopromide-carrying liposomes
      containing soy phosphatidyl glycerol.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine the
      feasibility of using iodinated liposomes as blood pool agents for computed
      tomography (CT) in nonhuman primates. MATERIALS AND METHODS: Five normal adult
      baboons (15-21 kg) were anesthetized and intravenously injected with iopromide
      containing soy phosphatidyl glycerol liposomes with a diameter of 195 nm. Each
      animal received a dose of 300 mg total iodine per kilogram (46% encapsulation).
      RESULTS: The animals tolerated the injections well, experiencing no measurable
      electrocardiographic changes, and recovered uneventfully from anesthesia.
      Sequential helical CT scans of the baboons from the base of the skull to the
      symphysis pubis acquired up to 40 minutes after injection showed persistent blood
      pool enhancement. Maximum mean enhancement of major vascular structures was 106
      HU at 1 minute after contrast medium injection. Mean blood pool enhancement was
      76, 72, and 67 HU at 10, 20, and 40 minutes after injection, respectively. Liver
      and spleen were enhanced by 40 and 41 HU, respectively, 40 minutes after
      injection. No significant enhancement was measured in the brain and pancreas.
      CONCLUSION: Soy phosphatidyl glycerol with iopromide liposomes produces prolonged
      vascular enhancement and has potential as a blood pool CT contrast agent in
      primates.

PMID- 10898036
TI  - Interpolation algorithms for digital mammography systems with multiple detectors.
AB  - RATIONALE AND OBJECTIVES: In some full-field digital mammography systems,
      multiple detectors are abutted together, and the physical gaps between adjacent
      detectors produce seams between the resultant subimages. In this study, a variety
      of interpolation algorithms for estimating the missing information in the seams
      were compared, and their effect on image quality was evaluated. MATERIALS AND
      METHODS: Eight representative interpolation algorithms were selected, including
      nearest neighbor, one-dimensional and two-dimensional weighting, mean value, one
      dimensional and two-dimensional polynomial, and one-dimensional and two
      dimensional cubic spline interpolation methods. These methods were applied to
      digital mammograms and phantom images. The effectiveness of each algorithm was
      evaluated for accuracy and geometric distortion. RESULTS: These interpolation
      algorithms offered similar accuracy in estimating missing image information. The
      weighting, polynomial, and cubic spline interpolation algorithms introduced less
      geometric distortion than the nearest neighbor and mean value interpolation
      algorithms. All algorithms were more effective in estimating larger, lower
      contrast features (such as breast masses) than in estimating smaller, higher
      contrast features (such as breast microcalcifications). Small microcalcifications
      within the seams cannot be recovered with interpolation. The probability of a
      microcalcification in a seam is small, however, and the failure to image a few
      microcalcifications of a cluster generally does not substantially alter
      diagnostic performance. CONCLUSION: In the development of full-field digital
      breast imaging systems, appropriate interpolation algorithms can satisfactorily
      fill in narrow gaps between adjacent detectors. The one-dimensional weighting
      interpolation method seems an effective and efficient choice.

PMID- 10898037
TI  - Blood pool and liver enhancement in CT with liposomal lodixanol: comparison with
      lohexol.
AB  - RATIONALE AND OBJECTIVES: The authors compared the time course and blood pool and
      hepatic enhancement of three different doses of liposomal iodixanol with those of
      iohexol. MATERIALS AND METHODS: A liposomal iodixanol formulation was prepared
      with 200 mg of iodine per milliliter total and 80 mg of iodine per milliliter
      encapsulated. Twelve normal New Zealand white rabbits divided into four groups
      received 75-, 100-, or 150-mg encapsulated iodine per kilogram doses of liposomal
      iodixanol or 2 mL/kg iohexol with 300 mg of iodine per milliliter. A liver
      section was scanned with serial computed tomography (CT) before the injection,
      immediately afterward, and at 1-minute intervals for 10 minutes. Region-of
      interest measurements of the aorta and liver were plotted at each time point, and
      contrast enhancement was plotted as a function of time and iodine dose. RESULTS:
      All liposomal iodixanol doses produced greater liver enhancement than iohexol.
      Results were significant (P < .05) for 100 mg and 150 mg iodine per kilogram dose
      groups at time points beyond 2 minutes. Peak hepatic enhancement (change in
      attenuation) was 54.9 HU +/- 7.6 with iohexol, compared with 59.6 HU +/- 6.1,
      73.3 HU +/- 3.6, and 104.1 HU +/- 8.8 for 75, 100, and 150 mg encapsulated iodine
      per kilogram doses, respectively. Hepatic enhancement increased rapidly after
      injection of liposomal iodixanol, plateauing 2-3 minutes later. Blood pool
      enhancement decreased rapidly. Steady-state liver enhancement with liposomal
      iodixanol increased linearly with dose. Aortic enhancement was greater with
      iohexol. CONCLUSION: Liposomal iodixanol yielded greater hepatic enhancement at
      lower total iodine doses than iohexol. Although liver enhancement occurred
      rapidly after injection, blood pool enhancement was brief.

PMID- 10898038
TI  - Use of popular culture as an educational tool in the training of radiology
      residents.

PMID- 10898039
TI  - Research as a profit center in radiology.

PMID- 10898040
TI  - Abnormalities of the pediatric foot.

PMID- 10898041
TI  - International MR Safety Central Web Site.

PMID- 10898042
TI  - New strategies for management of malnutrition in peritoneal dialysis patients.

PMID- 10898043
TI  - Chronic peritoneal dialysis in the elderly: a review.
AB  - During the past few decades, the pattern of end-stage renal disease has changed
      significantly with the emerging predominance of elderly patients. Because this
      heterogeneous population is characterized by a physiological decline in function
      of all organs, the nephrologist must contemplate the special needs of individual
      patients when they develop end-stage renal disease. Before the initiation of
      dialysis, these patients must be given detailed information to help them select
      the particular mode that will maximize their quality of life. According to
      available data, peritoneal dialysis offers some advantages for elderly patients,
      such as hemodynamic stability, steady-state metabolic control, good control of
      hypertension, independence from hospital, and avoidance of repeated vascular
      access. Early referral promotes the establishment of peritoneal access and
      minimizes the consequences of uremia, subsequent morbidity, and frequent
      hospitalization. Elderly patients are compliant and highly motivated to cooperate
      with their treatment. They have no higher modality-related complications than
      younger patients and their quality of life is satisfactory. Although most have
      comorbid conditions that interfere with self-performance of dialysis, such as
      impaired vision and reduced physical and mental activity, they can perform
      peritoneal dialysis successfully if they have a high level of family support.
      Patients who do not have family support may have successful peritoneal dialysis
      if they have access to a network of medical and social support, that is, private
      home nurses, rehabilitation and chronic care dialysis units, or nursing homes.

PMID- 10898044
TI  - Protein-losing enteropathy is associated with peritoneal functional abnormalities
      in peritoneal dialysis patients.
AB  - OBJECTIVE: To evaluate the relationship between acquired peritoneal transport
      disorders and the presence of protein-losing enteropathy (PLE), and their
      contribution to the protein malnutrition in peritoneal dialysis (PD) patients.
      PATIENTS AND METHODS: We studied 31 clinically stable PD patients that received a
      fat overload diet for 3 days. We measured intestinal absorption of fecal fat
      (normal < 6 g/24-hour stool) and nitrogen (normal < 2 g/24-hr stool), intestinal
      protein permeability [fecal clearance of alpha1-antitrypsin (Calpha1AT) (normal <
      12 mL/24-hr stool)], and nutritional markers [normalized protein nitrogen
      appearance (nPNA), half-life medium-term proteins, and body mass index].
      Peritoneal solute transport was measured by mass transfer coefficient (MTC), and
      water transport by peritoneal ultrafiltration (UF) capacity. To define protein
      maldigestion it was necessary to find high fecal nitrogen values with normal
      Calpha1AT; PLE was defined when both values were elevated. RESULTS: High fecal
      nitrogen (mean 2.1+/-1 g/24-hr stool) and fat (mean 5.8+/-3.6 g/24-hr stool) were
      found in 15 patients; 6 patients had high Calpha1AT levels (PLE). These 6
      patients showed a worse nutritional status: lower albumin (3.57+/-0.57 g/dL vs
      3.98+/-0.38 g/dL, p < 0.05) and transferrin (243+/-70 mg/dL vs 272+/-44.3 mg/dL,
      p < 0.05), as well as lower triglycerides (131.3+/-31.7 mg/dL vs 187+/-116 mg/dL,
      p< 0.05). Higher urea MTCs were found in 10 patients, normal in 7, and lower in
      14. Higher creatinine MTCs were found in 8 patients, normal in 15, and lower in
      8. Normal peritoneal UF capacity was found in 25 and lower in 6 patients. These 6
      patients showed higher urea and creatinine MTCs and Calpha1AT. A positive linear
      correlation between Calpha1AT, urea MTC (r = 0.56, p < 0.01), and creatinine MTC
      (r = 0.46, p < 0.01) was found. A similar situation occurred between Calpha1AT,
      fecal fat (r = 0.45, p < 0.05), and fecal nitrogen (r = 0.43, p < 0.05). Thirteen
      patients with previous history of peritonitis showed higher Calpha1AT than those
      without peritonitis (10.2+/-8 mL/24-hr stool vs 5.2+/-4.4 mL/24-hr stool, p <
      0.05). CONCLUSIONS: We confirm that protein and fat malabsorption, maldigestion,
      and PLE are present in some PD patients. Higher fecal Calpha1AT is associated
      with malnutrition and poorer showings of the viability markers of peritoneal
      membrane function.

PMID- 10898045
TI  - Reduced oxidative stress in hypoalbuminemic CAPD patients.
AB  - OBJECTIVE: Albumin is one of the plasma antioxidants. The higher incidence of
      cardiovascular disease in dialysis patients with hypoalbuminemia may be related
      to decreased antioxidant capacity resulting from low serum albumin. We evaluated
      malondialdehyde (MDA), a marker of oxidative stress, and total antioxidant
      capacity (TAC) in relation to serum albumin in continuous ambulatory peritoneal
      dialysis (CAPD) patients. PATIENTS AND METHODS: In this cross-sectional study, we
      measured MDA, TAC, albumin, uric acid (another important plasma antioxidant),
      prealbumin, and C-reactive protein (CRP) in the blood of 66 CAPD patients and 30
      normal controls.Twenty-two CAPD patients with albumin less than or equal to 3.5
      g/dL were divided into two groups: In the experimental group (n = 11), MDA,TAC,
      and CRP were measured before and after repeated infusion of 20% albumin 100 mL
      daily for 7 days. In the control group (n = 11), the same parameters were
      measured without albumin infusion. RESULTS: CAPD patients had lower albumin and
      higher MDA,TAC, and uric acid than normal controls. There were positive
      correlations between albumin and TAC or uric acid in CAPD patients. Contrary to
      our expectation, there was also positive correlation between albumin and MDA in
      CAPD patients (r = 0.37, p = 0.004). MDA showed a positive correlation with TAC.
      Uric acid was correlated with TAC. It did not, however, show correlation with
      MDA. Log CRP was negatively correlated with albumin, but did not show correlation
      with MDA or TAC. Prealbumin was correlated with MDA, TAC, albumin, and uric acid.
      Serum albumin in the experimental group increased from 2.5+/-0.3 g/dL to 3.6+/
      0.2 g/dL (p < 0.001) at the end of repeated infusions. No changes were seen in
      MDA, TAC, and CRP in either group. CONCLUSIONS: The present study suggests that
      lipid peroxidation is increased in CAPD patients and that this is not due to
      weakening of antioxidant defenses of plasma. Increased TAC was mainly caused by a
      higher level of uric acid. Reduced, rather than increased, MDA in hypoalbuminemic
      patients and lack of effects of albumin infusion on levels of MDA suggest that
      the frequent occurrence of cardiovascular disease in dialysis patients with
      hypoalbuminemia is not due to the decrease in antioxidant capacity resulting from
      low serum albumin.

PMID- 10898046
TI  - Phenotypic alterations of recruited eosinophils in peritoneal fluid eosinophilia.
AB  - OBJECTIVE: To characterize eosinophils and soluble factors in effluent from
      continuous ambulatory peritoneal dialysis (CAPD) patients and connect these
      findings to related conditions with eosinophilic accumulation. PATIENTS: Three
      newly started CAPD patients, two with peritoneal fluid eosinophilia (PFE) and one
      with bacteria-induced peritonitis. One patient with PFE was followed up for 10
      visits during a 7-month period. METHODS: Leukocytes were analyzed in dialysate
      and peripheral blood from the patients, by flow cytometry, and soluble mediators
      by ELISA or CAP technique. RESULTS: We found an increased number of neutrophils
      in the effluent from the patient with bacteria-induced peritonitis; accumulation
      of eosinophils in combination with negative cultures was noted in the patients
      with PFE. Increased levels of interleukin (IL)-5 and eosinophil cationic protein,
      but equal levels of eotaxin, were found in effluent from the PFE patients
      compared to the patient with neutrophilia. Peritoneal fluid eosinophils were
      activated by means of EG2, CD11b, CD9, and CD69 expression. Compared to blood
      eosinophils, the cytokine receptors for IL-5 and granulocyte-macrophage colony
      stimulating factor, but not IL-3, were down regulated. CONCLUSION: The finding of
      activated eosinophils in combination with IL-5 and eotaxin in PFE indicates
      existing similarities between PFE and conditions found during recruitment of
      eosinophils in allergic inflammatory responses.

PMID- 10898047
TI  - A survey of CAPD peritonitis management and outcomes in North and South Thames
      NHS regions (U.K.): support for the ISPD guidelines. International Society for
      Peritoneal Dialysis.
AB  - OBJECTIVE: This survey examined the current management of continuous ambulatory
      peritoneal dialysis (CAPD) peritonitis and the effectiveness of the various
      antibiotic protocols in use. DESIGN: The information required was elicited via a
      postal questionnaire. SETTING: The questionnaire was posted to each renal
      dialysis unit offering CAPD throughout the North and South Thames National Health
      Service regions. PATIENTS: All patients using CAPD at each responding unit were
      eligible for inclusion. MAIN OUTCOME MEASURES: Each unit provided details of
      their CAPD peritonitis episodes for 1997. Each unit's empirical treatment regimen
      for CAPD peritonitis was sought in addition to response rates. Also requested
      were numbers for peritonitis episodes, recurrences, and negative cultures, plus
      the peritonitis rate per patient-month. RESULTS: Thirteen units returned the
      questionnaire (87% of the survey population). Nine of the 13 units were using
      vancomycin regimens, with the remainder using cephalosporin regimens. The results
      were compared to the audit standards of the British Renal Association. Seventy
      percent of units reached the 80% mark for response rate; similar results were
      achieved with both the vancomycin and cephalosporin regimens. Ninety-two percent
      achieved the suggested peritonitis rate of 1 episode every 18 patient-months; 30%
      achieved the culture-negative rate of 10%. The average recurrence rate was 19%.
      CONCLUSION: The units contacted achieved most of the standards suggested by the
      British Renal Association; however, wide variations did exist. Recent guidelines
      have suggested avoiding vancomycin-based regimens in order to reduce the
      incidence of vancomycin resistance. The suggested regimen of a cephalosporin with
      an aminoglycoside seems to represent a suitable alternative.

PMID- 10898048
TI  - Dyslipidemia in peritoneal dialysis--relation to dialytic variables.
AB  - OBJECTIVE: To investigate whether the specific lipoprotein (LP) abnormalities of
      peritoneal dialysis (PD) are associated with functional variables of this mode of
      dialysis. DESIGN: A survey of the LP profile in relation to peritoneal dialysis
      capacity (PDC) variables. The LP profile was compared to that of a group of age-
      and sex-matched controls. SETTING: The Peritoneal Dialysis Unit at Sahlgrenska
      University Hospital in Gothenburg, Sweden. PATIENTS: Twenty-two nondiabetic PD
      patients (5 women, 17 men) who had been on PD for at least 6 months. MAIN OUTCOME
      MEASURES: The LP profile included plasma lipids, apolipoproteins (Apo), and
      individual ApoA- and ApoB-containing LP. The PDC measurement determined
      peritoneal glucose uptake, protein losses, effective peritoneal surface area, and
      total weekly creatinine clearance. RESULTS: The patients had been on PD for 6 to
      48 months (mean 15.3 months) and had a total weekly creatinine clearance of
      69.7+/-13.3 L/1.73 m2 body surface area, an average peritoneal glucose uptake
      corresponding to 446+/-162 kcal/24 hour, and a protein loss of 8.1+/-2.5 g/24 hr.
      The patients had significantly higher total cholesterol (7.1 mmol/L),VLDL
      cholesterol (1.0 mmol/L), LDL-cholesterol (4.7 mmol/L), and triglyceride levels
      (2.5 mmol/L); whereas the HDL-cholesterol level (1.2 mmol/L) was significantly
      lower than in controls. The PD patients had increased levels of ApoB-containing
      LPs, both of the cholesterol-rich LP-B and of the triglyceride-rich LP-B complex,
      reflected in higher plasma concentrations of ApoB, ApoC-III, and ApoE.
      Furthermore, they had significantly lower levels of LP-A-I:A-II, as well as of
      ApoA-I and ApoA-II. The LP-A-I:A-II and ApoA-II levels correlated inversely with
      the duration of PD treatment (r = 0.54, p < 0.01 and r = 0.52, p < 0.05,
      respectively). The ApoA-II level was inversely correlated with the peritoneal
      surface area (r = 0.53, p < 0.05). There were no other correlations between LP
      variables and PDC variables, nor did any of the LP variables correlate with
      peritoneal glucose uptake or protein losses. CONCLUSION: The proatherogenic
      lipoprotein profile of patients on PD is characterized by increased
      concentrations of cholesterol-rich and triglyceride-rich ApoB-containing LPs.
      While the duration of treatment appears to have some influence on the development
      of this type of dyslipidemia, the pathophysiological links to the dialysis mode
      must be further explored.

PMID- 10898049
TI  - High prevalence of hyperparathyroidism among peritoneal dialysis patients: a
      review of 176 patients.
AB  - OBJECTIVES: Parathyroid dysfunction continues to produce significant morbidity in
      dialysis patients. Since the introduction of low calcium dialysate for peritoneal
      dialysis (PD), no large studies have been done to determine the prevalence of
      parathyroid dysfunction in these patients. This study was done to assess the
      prevalence of parathyroid disease in the PD population and to determine the risk
      factors associated with this dysfunction. DESIGN: We analyzed data on 176
      patients who received PD at a single center between August 1998 and February
      1999. Clinical data, laboratory variables related to parathyroid function, and
      data pertaining to dialysis treatment and weekly drug dosing were obtained for
      each patient on two different occasions, approximately 3 months apart. Variables
      predictive of the development of parathyroid dysfunction were calculated by
      univariate and multivariate logistic regression analysis. RESULTS: Two-thirds of
      the patients surveyed had an abnormal intact parathyroid hormone (iPTH) level:
      47% had an iPTH level more than three times normal, the mean was 54.6+/-35.4
      pmol/L; 23% had an iPTH value below the upper limit of normal, here the mean was
      3.6+/-1.8 pmol/L. Diabetic patients had lower iPTH levels (22.2+/-28.4 pmol/L)
      than nondiabetics (33.9+/-34.8 pmol/L) (p = 0.02). On multivariate regression
      analysis, we found that age, duration of dialysis, Kt/V, serum bicarbonate, and
      serum ionized calcium levels did not significantly affect parathyroid function.
      Hyperphosphatemia was the only factor that was associated with the development of
      secondary hyperparathyroidism in this study population (p = 0.029). CONCLUSION:
      There is a high prevalence of hyperparathyroidism in the current PD population.
      Phosphate control is suboptimal and hyperphosphatemia is an independent risk
      factor for the development of hyperparathyroidism.

PMID- 10898050
TI  - Continuous ambulatory peritoneal dialysis is responsible for an increase in
      plasma norepinephrine.
AB  - OBJECTIVE: To investigate the reason for increasing norepinephrine (NE) levels
      reported in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS:
      Norepinephrine was measured in the plasma and peritoneal dialysate of CAPD
      patients (n = 22) and in the plasma and the urine of healthy subjects (n = 20).
      It was also measured in the plasma of patients with chronic renal failure (CRF)
      (n = 15) and patients on hemodialysis (HD) (n = 15). RESULTS: It was found that
      NE was increased in CAPD patients compared with healthy individuals (687+/-221
      pg/mL vs 199+/-25 pg/mL, p < 0.01). The daily removal of NE from the peritoneum
      of CAPD patients was lower compared with the amount of NE excreted in the urine
      of healthy subjects. Plasma NE increased after infusion of peritoneal dialysate.
      In 15 new patients on CAPD, it was found that NE plasma levels increased from
      329+/-67 pg/mL before initiation of dialysis, to 584+/-173 pg/mL after 12 months
      of treatment (p < 0.01). Finally, plasma NE in CAPD patients (687+/-221 pg/mL)
      was significantly higher compared with the already increased levels in patients
      on HD or with CRF (406+/-143 pg/mL and 378+/-142 pg/mL, respectively).
      CONCLUSIONS: It is concluded that CAPD in patients with end-stage renal disease
      is responsible for a progressive increase of plasma norepinephrine.

PMID- 10898051
TI  - Intermediate outcomes by race and ethnicity in peritoneal dialysis patients:
      results from the 1997 ESRD Core Indicators Project. National ESRD Core Indicators
      Workgroup.
AB  - BACKGROUND: Hispanics are the fastest growing minority group in the United
      States, and approximately 10% of all end-stage renal disease (ESRD) patients are
      Hispanic. Few data are available, however, regarding dialysis adequacy and anemia
      management in Hispanic patients receiving peritoneal dialysis in the U.S.
      METHODS: Data from the Health Care Financing Administration (HCFA) ESRD Core
      Indicators Project were used to assess racial and ethnic differences in selected
      intermediate outcomes for peritoneal dialysis patients. RESULTS: Of the 1219
      patients for whom data were available from the 1997 sample, 9% were Hispanic, 24%
      were non-Hispanic blacks, and 59% were non-Hispanic whites. Hispanics were more
      likely to have diabetes mellitus as a cause of ESRD compared to blacks or whites,
      and both Hispanics and blacks were younger than white patients (both p < 0.001).
      Although whites had higher weekly Kt/V and creatinine clearance values compared
      to blacks or Hispanics (p < 0.05), blacks had been dialyzing longer (p < 0.01)
      and were more likely to be anuric compared to the other two groups (p < 0.001).
      Blacks had significantly lower mean hematocrit values (p < 0.001) and a greater
      proportion of patients who had a hematocrit level less than 28% (p < 0.05)
      compared to Hispanics or whites, despite receiving significantly larger weekly
      mean epoetin alfa doses (p < 0.05) and having significantly higher mean serum
      ferritin concentrations (p < 0.01). Multivariate logistic regression analysis
      revealed significant differences by race/ethnicity for experiencing a weekly Kt/V
      urea < 2.0 and hypertension, but not for other intermediate outcomes examined
      (weekly creatinine clearance < 60 L/week/1.73 m2, Hct < 30%, and serum albumin <
      3.5/3.2 g/dL). CONCLUSION: Hispanics had adequacy values similar to blacks and
      anemia parameters similar to whites. Additional studies are needed to determine
      the etiologies of the differences in intermediate outcomes by racial and ethnic
      groupings in peritoneal dialysis patients.

PMID- 10898052
TI  - HomeChoice automated peritoneal dialysis machines: the impact of reuse of tubing
      and cassettes.

PMID- 10898053
TI  - The rate, risk factors, and outcome of fungal peritonitis in CAPD patients:
      experience in Turkey.

PMID- 10898054
TI  - Sclerosing encapsulating peritonitis after renal transplantation. Does it make
      sense?

PMID- 10898055
TI  - Iatrogenic peritonitis: the need for prophylaxis.

PMID- 10898056
TI  - Impact of total solute clearance on clinical outcomes in Korean CAPD patients.

PMID- 10898057
TI  - CAPD peritonitis due to Serratia plymuthica.

PMID- 10898058
TI  - Successful pregnancy complicated with peritonitis in a 25-year-old Turkish CAPD
      patient.

PMID- 10898059
TI  - Lean body mass calculation by creatinine kinetics in CAPD. Is it only a measure
      of somatic nutrition?

PMID- 10898060
TI  - No benefit in using nystatin prophylaxis against fungal peritonitis in peritoneal
      dialysis patients.

PMID- 10898061
TI  - Peritonitis prevention in CAPD: to mask or not?
AB  - OBJECTIVE: To assess the efficacy of wearing a face mask to prevent peritonitis
      during continuous ambulatory peritoneal dialysis (CAPD) bag exchange. SETTING:
      Renal unit at a university hospital. PATIENTS: Two groups of patients on CAPD
      were compared: those performing bag exchange with (n = 24) and those without a
      face mask (n = 40). OUTCOMES: Occurrence of first episode of peritonitis and
      total number of episodes. RESULTS: No difference was found between groups with
      respect to probability of developing the first episode of peritonitis (p =
      0.757). Patients holding university degrees had evidence of protection, with
      borderline significance [relative risk (RR) 0.52; confidence interval (CI) 95%,
      0.23 -1.18; p= 0.109]. Cox's proportional hazard regression analysis also
      demonstrated a significant protective factor for patients with university level
      education (RR 0.42; Cl 95%, 0.18 - 0.98; p = 0.04). Incidence of peritonitis was
      not significantly different between groups: with-mask group had 1.0 episode/year,
      and without-mask group had 0.94 episodes/year. Staphylococcus epidermidis was the
      most commonly identified agent. Staphylococcus aureus was found more frequently
      in the with-mask group (p = 0.003). Peritonitis due to Streptococcus viridans and
      Enterococci were detected only in the without-mask group. CONCLUSION: The current
      study suggests that routine use of face masks during CAPD bag exchanges may be
      unnecessary and could be discontinued.

PMID- 10898063
TI  - Literature. May-June 2000.

PMID- 10898062
TI  - PD nurses in Hong Kong: competency, self-motivation, and commitment. Nursing
      application: beyond maintaining PD technique survival.

PMID- 10898064
TI  - Will rheumatoid arthritis still be an important health problem in the 21st
      century?

PMID- 10898065
TI  - Hormone replacement therapy in women with rheumatic diseases.
AB  - Hormone replacement therapy (HRT) for the treatment of menopausal symptoms and
      for the prevention of osteoporosis and cardiovascular diseases has clearly
      increased during the last decades. Women with rheumatic diseases, especially when
      using corticosteroids, are in a high risk of osteoporotic fractures and
      atherosclerotic disease, which cause significant morbidity and mortality in later
      life. In this review, the benefits and risks of HRT in postmenopausal women are
      reviewed in general and, in particular, in women with rheumatic diseases.

PMID- 10898066
TI  - Increased expression of CD23 in rheumatoid synovitis.
AB  - OBJECTIVE: Soluble (s)CD23 is a potent macrophage stimulator. High levels of this
      molecule have been reported in rheumatoid arthritis (RA) serum. We investigated
      the expression of CD23 and its ligands in rheumatoid synovial fluid and cells.
      METHODS: Levels of sCD23, and cellular expression of CD23 and its ligands CD21,
      CD11b, and CD11c were measured in synovial fluid (SF) of RA patients and in blood
      of RA patients and controls. RESULTS: SF contained higher levels of sCD23 than
      either rheumatoid or normal sera (median 4.8, 3.16,and 1.13 ng/ml respectively, p
      <0.01). Synovial CD23 was found to be expressed principally on macrophages. While
      little CD21 expression was detected, CD11b and CD11c were both expressed at high
      levels, particularly on macrophages. CONCLUSIONS: Soluble CD23 is present in high
      levels in RA synovial fluid. Macrophages appear to be the principal source.
      Macrophages also express ligands for sCD23, and may therefore also be the targets
      of this potent pro-inflammatory molecule.

PMID- 10898067
TI  - Methotrexate in the treatment of ankylosing spondylitis.
AB  - The authors carried out an open prospective study analyzing methotrexate (MTX)
      efficacy and toxicity in 34 patients with ankylosing spondylitis (AS) for a
      period of one year. All the patients presented with active axial disease,
      characterized by inflammatory spinal pain, prolonged morning stiffness,
      erythrocyte sedimentation rate (ESR) > or = 25 mm, and failure on treatment with
      non-steroidal anti-inflammatory drugs for a period of more than two years. MTX
      was taken at a single weekly intramuscular dose of 12.5 mg. Thirty-one patients
      (91%) concluded treatment. Eighteen patients (53%) were considered responders to
      MTX; most of them presented peripheral arthritis. Despite clinical improvement,
      axial measures were unaltered at the end of the study. The mean value of ESR
      decreased significantly at the end of the treatment (p=0.0001), predominantly in
      the responders group. Side effects were observed in 23 patients (68%) and
      included dyspeptic syndrome, transient elevation of liver enzymes, and dizziness.
      The results of this one year open study suggest that MTX can be an efficient drug
      in the treatment of AS.

PMID- 10898068
TI  - No permanent reduction in bone mineral density during treatment of polymyalgia
      rheumatica and temporal arteritis using low dose corticosteroids.
AB  - The objective of the study was to examine bone mineral density (BMD) in patients
      with polymyalgia rheumatica (PMR) or temporal arteritis (TA) currently or
      previously treated with prednisolone. BMD (using single or dual x-ray
      absorptiometry) was measured in radius, spine, and hip in 26 currently and 28
      previously prednisolone treated patients with PMR (n = 38) or TA (n = 16). The
      prednisolone treated patients were compared to 30 newly diagnosed PMR (n = 26) or
      TA patients (n=4) examined prior to start of prednisolone, and 70 healthy
      controls. No statistically significant differences were found between the groups
      regarding age, height, weight, and gender. For current users of prednisolone, the
      mean daily dose was 6.5 mg, the mean cumulative dose 7.7 grams, and for previous
      users 5.6 mg and 6.6 grams, respectively. No statistically significant
      differences in BMD at the different measurement sites were found between
      prednisolone treated patients and the two control groups. Similarly, no
      significant differences in BMD were found between current and previous users of
      prednisolone and between the prednisolone treated PMR and TA patients. In
      conclusion, BMD is not substantially reduced in PMR and TA patients currently or
      previously treated with mean low dose prednisolone. However, a tendency to a
      lower BMD was found in PMR/TA patients currently treated with prednisolone and in
      the prednisolone treated TA patients.

PMID- 10898069
TI  - Usefulness of high resolution US in the evaluation of effusion in osteoarthritic
      first carpometacarpal joint.
AB  - OBJECTIVE: The aim of this study is to provide a reproducible and quantitative
      sonographic method for evaluation of effusion in the first carpometacarpal joint
      in osteoarthritis. METHODS: High resolution sonography of the carpometacarpal
      joint of the thumb was carried out in 20 normal joints and in 57 joints from
      patients with osteoarthritis. A 10 MHz transducer was used. RESULTS: The
      articular cavity appeared as a hypoechoic triangular area. In normal joints the
      mean values obtained by measuring the distance between the apex and the base of
      the triangle was 2.89 mm (SD 0.22). In osteoarthritic joints it was significantly
      increased (p<0.001). The authors assert that the presence of effusion is very
      likely if the value is >3.33 mm (mean+2 SD). CONCLUSIONS: Sonography provides
      useful, reproducible, and quantitative data for detection of effusion within the
      first carpometacarpal joint.

PMID- 10898070
TI  - Protracted febrile myalgia of familial Mediterranean fever. Mutation analysis and
      clinical correlations.
AB  - Protracted febrile myalgia (PFM) is a rare form of vasculitic disease that
      affects patients with familial Mediterranean fever (FMF). Mutation analysis
      performed in 15 patients who suffered from this disorder showed that 9 of the 15
      patients were homozygous for M694V. FMF in these 9 patients was associated with
      more severe symptoms compared to a group of 30 M694V homozygous FMF patients
      without PFM.

PMID- 10898071
TI  - Anxiety and depression in a community-based rheumatoid arthritis population.
AB  - OBJECTIVE: To assess anxiety and depression and their explanatory factors in
      rheumatoid arthritis (RA) in a community-based population. METHODS: The subscales
      of the Arthritis Impact Measurement Scales (AIMS) for anxiety and depression were
      used, and the Health Assessment Questionnaire (HAQ) was used for the assessment
      of disability. Cross-tabulation and multivariate logistic regression analysis
      were used to evaluate which variables best describe the patients with either high
      or low depression and anxiety scores. RESULTS: Nearly 20% of our patients had
      probable depression (AIMS depression subscale score > or =4), a figure comparable
      to earlier hospital-based series. Most of the AIMS anxiety subscale variability
      was explained by poor physical function and the male sex, while the AIMS
      depression subscale variability was mostly explained by poor physical function,
      comorbidities, and social inactivity. CONCLUSION: In our cross-sectional,
      community-based RA series, depression was equal to the figures previously
      reported from hospital-based series. Poor physical function was a powerful
      explanatory factor of both depression and anxiety.

PMID- 10898072
TI  - Pes anserinus tendino-bursitis: what are we talking about?
AB  - We studied the ultrasonographic (US) features of the pes anserinus insersion (PA)
      and subcutaneous medial knee fat in patients clinically diagnosed of pes
      anserinus tendino-bursitis (PATB) syndrome. Thirty seven consecutive patients
      with suspected PATB were clinically evaluated and their knees examined using a
      7.5 MHz linear probe. In twenty-three patients with unilateral clinical PATB
      (group A) the painful knee was compared with their painless opposite knee. Six
      patients with bilateral clinical PATB (group B) were compared with 6 healthy
      controls (group C). All patients were women with radiographic knee osteoarthritis
      in 93% and body mass index > 27 in 75%. US pes anserinus tendinitis was found in
      one symptomatic knee and pes anserinus bursitis in two symptomatic knees and in
      one asymptomatic knee. No US signs of panniculitis were found in patients and
      controls. In conclusion, patients diagnosed of PATB syndrome in rheumatology
      rarely have US tendinitis or bursitis of the PA.

PMID- 10898073
TI  - Erythrocyte-methotrexate and disease activity in children treated with oral
      methotrexate for juvenile chronic arthritis.
AB  - The concentration of methotrexate (MTX) in erythrocytes (E-MTX) was measured
      twice with three months interval in 21 children suffering from juvenile chronic
      arthritis (JCA). At the same time joint score, visual analogue scale (VAS), and
      laboratory parameters (CRP, WBC, PMNs, and ALAT) were obtained. There was only a
      weak insignificant correlation between the dose of MTX/m2 and E-MTX (r=0.24,
      p=0.11). No significant relations between the clinical or laboratory parameters
      and E-MTX was found. However, ALAT above normal range was associated with a lower
      dose of MTX (p=0.02) and lower VAS (p=0.02), indicating that toxicity may be
      associated with less articular discomfort. At present we consider routine
      determination of E-MTX in children with JCA of limited value.

PMID- 10898074
TI  - Elevation of only one rheumatoid factor isotype is not associated with increased
      prevalence of rheumatoid arthritis--a population based study.
AB  - OBJECTIVE: To analyse the relationship between different rheumatoid factor (RF)
      isotype patterns and the prevalence of RA. METHODS: Serum samples, collected
      between 1973 and 1983 from nearly 14,000 randomly selected individuals, were
      screened for elevation of RF. In 1987, 173 RF positive and 156 matched RF
      negative participants were evaluated clinically. RESULTS: Participants with
      elevation of only one RF isotype, most commonly IgM, did not have significantly
      higher prevalence of RA than the RF negative controls. Of the 17 RF positive
      individuals who were diagnosed with RA, 14 (82%) had a combined elevation of IgM
      and IgA RF. CONCLUSION: In contrast to a combined elevation of IgM and IgA RF,
      elevation of only one RF isotype may not be a significant risk factor for the
      development of RA.

PMID- 10898075
TI  - Combined use of cyclosporine A and methotrexate in refractory polymyositis.
AB  - Polymyositis is an inflammatory muscle disease with unknown cause that is
      characterized by progressive weakness of the proximal muscles. Limited
      information is available concerning the effectiveness of the combination therapy
      with cyclosporine A and methotrexate in reducing myositis activity. We describe
      here a female patient with polymyositis who showed resistance to pulse
      corticosteroid therapy. Neither the combination of azathioprine (100 mg/day) nor
      methotrexate (10 mg/week) with corticosteroids decreased the value of creatine
      phosphokinase. Normalization of the creatine phosphokinase level as well as
      improvement of muscle strength was obtained only when low-dose cyclosporine A (3
      mg/kg/day) was combined with methotrexate.

PMID- 10898076
TI  - Extracorporeal membrane oxygenation for the management of respiratory failure due
      to ANCA-associated vasculitis.
AB  - We present here two patients whose near fatal respiratory distress was caused by
      pulmonary hemorrhage, and who were treated successfully by extracorporeal
      membrane oxygenation (ECMO). The underlying disease was anti-neutrophil
      cytoplasmic antibody (ANCA)-associated systemic vasculitis. They were initially
      treated with methylprednisolone pulse therapy along with cyclophosphamide.
      However, their respiratory failure progressed with a low PaO2/FiO2 ratio (< 100
      mmHg) despite mechanical ventilation, and ECMO was initiated. After several days,
      the pulmonary hemorrhage subsided, and the patients were weaned successfully from
      ECMO. We suggest that ECMO may be used to manage life-threatening pulmonary
      hemorrhage in patients suffering from ANCA-associated systemic vasculitis.

PMID- 10898077
TI  - Isolated pulmonary hypertension in diffuse cutaneous systemic sclerosis
      successfully treated with long-term plasma exchange.
AB  - Isolated pulmonary hypertension (PHT) in patients with diffuse cutaneous systemic
      sclerosis (dSSc) is one of the most severe complication. Here we report the case
      of a 22 year-old white woman with anti-U3RNP antibody-positive dSSc complicated
      by severe, isolated PHT successfully treated with long-term plasma exchange. This
      beneficial effect persisted for two years, even after plasma exchange
      discontinuation. This is the first observation of isolated PHT in dSSc responsive
      to plasma exchange therapy.

PMID- 10898078
TI  - Cryoglobulinemic vasculitis resistant to intermittent intravenous pulse
      cyclophosphamide therapy.
AB  - We report on a 78-year-old patient with severe disease manifestations including
      polyneuropathy and clinically suspected secondary temporal arteritis due to
      hepatitis C virus-associated cryoglobulinemic vasculitis (CV). Despite
      intermittent intravenous pulse cyclophosphamide therapy and oral corticosteroid
      therapy her condition further deteriorated. Only oral cyclophosphamide therapy
      with high-dose corticosteroid and plasmapheresis was efficient in inducing a
      remission of her CV. This case report demonstrates that pulse cyclophosphamide
      therapy may not be sufficient to control severe manifestations of
      cryoglobulinemic vasculitis.

PMID- 10898079
TI  - Osteoporosis in patients with rheumatoid arthritis: tip of the iceberg?

PMID- 10898080
TI  - The prevalence of rheumatoid arthritis in Sweden.

PMID- 10898081
TI  - Lipoinsulin encapsulated alginate-chitosan capsules: intestinal delivery in
      diabetic rats.
AB  - An oral formulation based on liposome encapsulated alginate-chitosan gel capsules
      was developed for insulin delivery for the treatment of diabetes. Liposome
      encapsulation helped to increase the encapsulation efficiency of insulin in
      alginate-chitosan capsules. This formulation delivers insulin in the neutral
      environment of the intestine, by-passing the acidic media in the stomach, with
      increased drug absorption and bioavailability. Oral administration of this
      formulation was found to reduce blood glucose levels when tested in diabetic
      rats.

PMID- 10898082
TI  - The preparation and drug-release behaviour of CTA/EC and PMS/EC composite
      microcapsules.
AB  - A cellulose triacetate (CTA) and three different molecular weights of poly(alpha
      methyl styrene) (PMS) were used as co-wall materials to prepare composite
      microcapsules with ethylcellulose (EC). A non-solvent-addition phase-separation
      method was used. The core material was theophylline (TH) and the solvent-non
      solvent pair was dichloromethane-n-hexane, and the drug-release rates of the
      microcapsules prepared from these two types of co-wall materials were compared.
      The effects of their phase-separation range on the properties of the
      microcapsules, such as particle size, release rate and the morphology of the
      microcapsules are also discussed. The release rate of microcapsules was also
      affected by the compatibility of the co-wall materials and the EC. The
      dissolution studies indicated that the drug-release time of CTA/EC and PMS/EC
      composite microcapsules was sustained to 10 and 3.5 times, respectively, in
      comparison with that for pure EC microcapsules.

PMID- 10898083
TI  - Sustained release microspheres of metoclopramide using poly(D,L-lactide-co
      glycolide) copolymers.
AB  - Metoclopramide was encapsulated with poly(D,L-lactide co glycolide) copolymers of
      different molecular weights using the emulsification/solvent evaporation
      technique. These polymers included poly(D,L-lactide-co-glycolide) 50:50 with
      inherent viscosity (i.v.) 0.2, and average molecular weight 8000, poly(D,L
      lactide-co-glycolide) 50:50 with i.v. 0.8 and average molecular weight 98000 and
      poly(D,L-lactide-co-glycolide) 85:15 with i.v. 1.4 and average molecular weight
      220000. The effect of the polymers' molecular weights as well as the polymer-to
      drug ratios on the yield, the particle size distribution, and the drug content of
      the microspheres was investigated. The release rate of the drug was studied for
      96 h in a phosphate buffer of pH 7.4. The study also investigated the effect of
      the new poly(lactide-co-glycolide)-H series on the characteristics of the
      prepared microspheres. Data revealed that a higher yield was obtained with
      polymers of lower molecular weights. A lower yield was also obtained with
      increasing the drug-to-polymer ratios for all the investigated polymers. The drug
      content of the microspheres was lower than expected, ranging from 49-85%, which
      suggested a chemical interaction between the drug and the polymers, as proved by
      differential scanning calorimetry (DSC) and infra red (IR) studies. A higher
      interaction was obtained with the H-series of the copolymers. The release of the
      drug mainly followed zero order kinetics on increasing either the polymers'
      molecular weights or the polymer-to-drug ratios. Diffusion kinetics was observed
      only with those batches prepared with low polymer-to-drug ratios. The release
      rate was a function of both the polymers' molecular weights and the drug-to
      polymer ratios.

PMID- 10898084
TI  - Improved preparation and physical studies of polybutylcyanoacrylate nanocapsules.
AB  - An improved method for the preparation of alkylcyanoacrylate nanocapsules is
      proposed that involves the intermediate synthesis of a well defined adduct of a
      single monomer unit to an ethanol molecule. It leads to thinner capsule walls
      and, generally, to a more reproducible capsule structure. The chemical
      composition of the intermediate organic phase has been studied by nuclear
      magnetic resonance spectroscopy. The morphology and size of resulting structures
      is analysed, applying analytical ultracentrifugation and light microscopic
      particle tracking. The sizes of capsules prepared in the described manner depend
      on the concentrations of the oil and the monomer components, as is shown by the
      results of a set of experiments following a simple factorial design.

PMID- 10898085
TI  - Urea-formaldehyde nanocapsules for the controlled release of diclofenac sodium.
AB  - Urea-formaldehyde (UF), polymerized in situ in aqueous media, is a rigid polymer
      that can be used in the controlled release of bioactive molecules. During the
      process of polymerization, liquid neem seed oil (NSO) was encapsulated at three
      different loadings, which was then replaced by diclofenac sodium (DS), the
      presence of which was confirmed by FTIR spectra. The nanocapsules thus prepared
      were evaluated for percentage loading of the drug, particle size and release
      characteristics. Thermal analysis and x-ray data were obtained to understand the
      physical nature of the encapsulated drug. The surface characteristics of the
      nanocapsules were studied using a scanning electron microscope. Particles in the
      size range around 500 nm were obtained. The percentage loading efficiency of NSO
      was approximately 90-95, whereas for DS, the loading efficiency was only 50-60%.
      Complete release of the drug from the matrices occurred in 24 h, whereas, at 8 h
      only 60% of the drug was released.

PMID- 10898086
TI  - Scintigraphic imaging of infections with 99m-Tc-labelled glutathione liposomes.
AB  - In this study, liposomes containing glutathione were evaluated to detect
      infection in mice. Glutathione liposomes were labelled by using 99mTc-labelled
      HMPAO (hexamethyl propylamine oxime). Mice were infected in the thigh by
      intramuscular injection with turbentine. Labelled liposomes were applied to the
      tail vein of the mice intravenously. At fixed time intervals they were
      sacrificed. The animals were imaged under a gamma camera. Then, tissue samples
      were excised and radioactivity of all organs was counted. Abscess-to-muscle,
      abscess-to-liver, and abscess-to-spleen ratios were calculated. The ratios of
      abscess-to-muscle were found to be 1.6 and 11.6 at 1 h and 24 h, respectively.
      According to these data, the abscess can be defined at 1 h and it became more
      clear with time.

PMID- 10898087
TI  - Effects of salt addition on the microencapsulation of proteins using W/O/W double
      emulsion technique.
AB  - The influence of co-encapsulation of stabilizing additives together with BSA on
      microsphere characteristics using the modified water-in-oil-in-water emulsion
      solvent evaporation (W/O/W) method was investigated. For this purpose, poly(L
      lactide) microspheres containing bovine serum albumin (BSA) were prepared. The
      morphology, porosity, specific surface area, particle size, encapsulation
      efficiency and kinetics of drug release of protein loaded microspheres were
      analysed in relation to the influence of co-encapsulated stabilizing additives
      such as electrolytes. High salt concentrations in the internal (W1) aqueous
      phase, often necessary to stabilize protein or antigen solutions, led to an
      increase in particle size, particle size distribution, porosity and specific
      surface area. Bulk density and encapsulation efficiency decreased. The release
      profile was characterized by a high initial burst due to the highly porous
      structure. Addition of salt to the external or continuous water phase (W2),
      however, stabilized the encapsulation process and, therefore, resulted in
      improved microsphere characteristics as a dense morphology, a reduced initial
      burst release, a drastically increased bulk density and encapsulation efficiency.
      Analysis of the specific surface area (BET) showed that the addition of salt to
      W2, regardless of the salt concentration in the W1 phase, decreased the surface
      area of the microspheres approximately 23-fold. Microsphere properties were
      influenced by salts additions through the osmotic pressure gradients between the
      two aqueous phases and the water flux during microsphere formation. Release
      profiles and encapsulation efficiencies correlated well with the porosity and the
      surface area of microspheres. Furthermore, the influence of a low molecular
      weight drug and different time-points of salt addition to W2 on microsphere
      characteristics were studied by encapsulation of acid orange 63 (AO63),
      confirming the results obtained with BSA. This study suggests that modification
      of the external water phase by adding salts is a simple and efficient method to
      encapsulate stabilized protein solution, with high encapsulation efficiency and
      good microsphere characteristics.

PMID- 10898088
TI  - Influence of various technological parameters on the preparation of spray-dried
      poly(epsilon-caprolactone) microparticles containing a model antigen.
AB  - This work evaluates the efficacy of the spray-drying technique to prepare
      poly(epsilon-caprolactone) (PCL) microparticles containing an entrapped model
      antigen (bovine albumin, BSA). The presence of a stabiliser was found to be an
      important parameter when preparing PCL microparticles containing a hydrophilic
      antigen. The effect of various technological parameters (concentration of the
      polymer and protein solutions, organic/aqueous phases ratio, nature of solvents
      and emulsion parameters such as duration and speed of agitation) on microparticle
      morphology and size, BSA entrapment and encapsulation efficiency was studied.
      Microparticles were characterized by a mean size from 9.56+/-0.25 to 24.31+/-2.87
      microm and a BSA entrapment from 0.80+/-0.02 to 24.21+/-0.23% (w/w). SDS-PAGE
      electrophoresis and isoelectric focusing (IEF) confirmed the conservation of the
      physicochemical characteristics of the BSA entrapped within PCL microparticles
      produced by spray-drying. Together, these results showed that spray-drying is an
      efficient technique to overcome the key obstacle that represents the scaling-up
      of the manufacturing process to produce sufficient quantities of vaccine for
      clinical trials and, ultimately, commercialization.

PMID- 10898089
TI  - The influence of magnesium stearate on the characteristics of mucoadhesive
      microspheres.
AB  - Microspheres containing the mucoadhesive polymer chitosan hydrochloride, with
      matrix polymer Eudragit RS, pipemidic acid as a model drug and agglomeration
      preventing agent magnesium stearate were prepared by the solvent evaporation
      method. The amount of magnesium stearate was varied and the following methods
      were used for microsphere evaluation: sieve analysis, drug content and
      dissolution determination, scanning electron microscopy, x-ray diffractometry,
      DSC and FTIR spectroscopy. The results showed that average particle size
      decreased with increasing amount of magnesium stearate used for microsphere
      preparation. This is probably a consequence of stabilization of the emulsion
      droplets with magnesium stearate. Higher pipemidic acid content in the
      microspheres was observed in larger particle size fractions and when higher
      amounts of magnesium stearate were used. It was also found that these two
      parameters significantly influenced the dissolution rate. The important reason
      for the differences in drug content in microspheres of different particle sizes
      is the diffusion of pipemidic acid from the acetone droplets in liquid paraffin
      during the preparation procedure. The physical state of pipemidic acid changed
      from crystalline to mostly amorphous with its incorporation in microspheres, as
      shown by x-ray diffractometry and differential scanning calorimetry. No
      differences were observed in the physical state of pipemidic acid and in
      microsphere shape and surface between different size fractions of microspheres,
      prepared with different amounts of magnesium stearate. Additionally, no
      correlation between the physical state of the drug in different microspheres and
      their biopharmaceutical properties was found.

PMID- 10898090
TI  - Evaluation of 99mTc labelled poly lactic acid microspheres for diagnostic
      radioembolization.
AB  - Radioembolization is used in diagnostic imaging of the lungs and for
      radioembolization therapy of hepatic tumours. Presently, 99mTc labelled
      macroaggregates or microspheres of human serum albumin (HAM) are used for this
      purpose. Poly lactic acid (PLA) is biodegradable, like HAM, and, unlike HAM, is
      not a blood product. The aim of the present study was to evaluate the uptake and
      biodegradation of PLA microspheres in lungs. PLA (MW = 48720 Da) microspheres of
      1.0-100 microm (mean = 39.5 microm) in diameter were prepared by solvent
      evaporation from methylene chloride. They were labelled with 99mTc by stannous
      chloride reduction at pH 3, with an efficiency of 98% and a stability of 96% at
      24 h. For biodistribution studies, 15 mice were i.v. injected with 20 microCi
      99mTc-PLA microspheres in 0.1 ml and sacrificed at 15 min, 1, 3, 6 and 24 h
      (three at each time point). All the organs were removed, weighed and counted
      against a standard prepared from 1/100 dilution of the injected radioactivity.
      Some mice were similarly injected and sacrificed at 30 min, 15 and 30 days. The
      lungs were removed and frozen, and 10 microm sections were obtained, stained with
      haemotoxylin and eosin and examined under a light microscope. Five rabbits were
      i.v. injected with 1 mCi of 99mTc-PLA microspheres. Scintigrams were obtained at
      various intervals up to 24 h. In mice, the lung uptake was significant at 30 min
      1h post-injection. In rabbits, the lungs were the only organs visualized up to 24
      h. Microscopic examination of tissue sections demonstrated slow biodegradation of
      PLA particles. In conclusion; (1) The high lung uptake obtained in mice and
      rabbits indicates the suitability of PLA microspheres for lung imaging, and (2)
      although the slow biodegradation rate might be a disadvantage in patients with
      lung disorders in diagnostic studies, it may be an advantage in therapeutic
      applications with radionuclides which have long physical half lives.

PMID- 10898091
TI  - Literature alerts.

PMID- 10898092
TI  - Up-regulation of endothelin-1 in gastric mucosal inflammatory responses to
      Helicobacter pylori Lipopolysaccharide: effect of omeprazole and sucralfate.
AB  - BACKGROUND: Helicobacter pylori is recognized as a primary etiologic factor in
      the development of gastric disease and the product of particular significance to
      the virulent action of the bacterium is its cell wall lipopolysaccharide. We
      applied the animal model of H. pylori lipopolysaccharide-induced acute gastritis
      to study the effect of antiulcer agents, omeprazole and sucralfate, on the course
      of mucosal inflammatory responses by analyzing the interplay between the extent
      of epithelial cell apoptosis and the mucosal expression of endothelin-1 (ET-1),
      tumor necrosis factor-alpha (TNF-alpha), and the activity of constitutive (cNOS)
      and inducible (NOS-2) nitric oxide synthase. METHODS: Rats pretreated twice daily
      for 3 consecutive days with omeprazole at 40 mg/kg, sucralfate at 100 mg/kg or
      the vehicle, were subjected to intragastric application of H. pylori
      lipopolysaccharide at 50 microg/animal, and after 2, 4, and 10 additional days on
      the antiulcer drug or vehicle regimen their mucosal tissue used for histologic
      and biochemical assessment. RESULTS: In the absence of antiulcer agents, H.
      pylori lipopolysaccharide elicited within 2 days a pattern of acute mucosal
      inflammatory responses accompanied by a massive epithelial cell apoptosis, a 2.9
      fold increase in the mucosal expression of ET-1, an 11.7-fold enhancement in TNF
      alpha, and a 9.3-fold increase in NOS-2, while cNOS activity showed a 5.5-fold
      decrease. The extent of mucosal inflammatory involvement reached a maximum by the
      4th day and showed a decline by the 10th day. This was reflected in a marked
      reduction in epithelial cell apoptosis, decrease in the mucosal expression of ET
      1, TNF-alpha and NOS-2, and the recovery in cNOS activity. Comparing to the
      vehicle controls, treatment with proton pump inhibitor, omeprazole, led at the
      end of a 10 day period to a 48.3% reduction in the extent of mucosal inflammatory
      involvement elicited by H. pylori lipopolysaccharide, while a 74.2% reduction in
      the mucosal inflammatory involvement was achieved with gastroprotective agent,
      sucralfate. Moreover, this advantage of sucralfate over omeprazole in countering
      the lipopolysaccharide-induced changes was reflected at the end of 10 day
      treatment period in a 20.4% greater decrease in apoptosis, a 47.5% greater
      reduction in TNF-alpha and a 50.7% greater reduction in ET-1. However, both
      agents exerted similar influence on the restoration of gastric mucosal cNOS
      activity and showed a comparable effect at the end of a 10 day treatment in
      countering the lipopolysaccharide-induced increase in the expression of NOS-2.
      CONCLUSIONS: The findings suggest that an increase in the mucosal ET-1 level
      elicited by H. pylori lipopolysaccharide, combined with a decline in cNOS may be
      responsible for the induction of TNF-alpha and triggering the inflammatory
      process. We also show that sucralfate exhibits greater efficacy than omeprazole
      in suppressing the H. pylori-induced mucosal inflammatory responses. This
      property of sucralfate may well be due to its ability to suppress the mucosal
      rise in ET-1.

PMID- 10898093
TI  - Effect of adrenalectomy and corticosterone on cocaine-induced sensitization in
      rats.
AB  - Effects of adrenalectomy (ADX) and corticosterone (CORT) on the development and
      expression of sensitization to the locomotor effect of cocaine (COC) were studied
      in rats. Sensitization was evoked by 5 daily injections of COC (10 mg/kg) and
      measured after a challenge dose of the drug (10 mg/kg) after a 5-day withdrawal
      (on day 10 of the experiment). ADX, performed before the start of COC
      administration, completely blocked the manifestation of COC-induced
      sensitization. In contrast, ADX performed on animals already sensitized to COC
      did not affect the sensitized locomotor activity response to a challenge dose of
      COC (on day 18). Pretreatment with CORT, 10 mg/kg, but not 5 mg/kg, before each
      of the 5 daily COC injections facilitated the development of COC sensitization,
      tested after a 5-day withdrawal. When pretreated with CORT alone (10 mg/kg), the
      challenge dose of COC administered on day 10 induced cross-sensitization to CORT.
      CORT (10 mg/kg) injected acutely before COC on day 10, potentiated the expression
      of COC sensitization. When given alone, on day 10 CORT (5-10 mg/kg) induced an
      increase in the locomotor activity of rats pretreated daily (5 injections) with
      COC. No drug treatment induced conditioned locomotion, as measured after saline
      challenge on day 8. Our results indicate that CORT facilitates the development
      and expression of COC sensitization, while ADX blocks the initiation of the
      behavioral phenomenon only. Moreover, there takes place cross-sensitization
      between CORT and COC, which indicates a close relationship between the drug
      related mechanism and behavioral sensitization.

PMID- 10898094
TI  - Cortical localization of dopamine D4 receptors in the rat brain-
      immunocytochemical study.
AB  - Using polyclonal antibody against dopamine D4 receptor we investigated cortical
      distribution of D4 receptors, with the special emphasis on regions of the
      prefrontal cortex. Prefrontal cortex is regarded as a target for neuroleptic
      drugs, and engaged in the regulation of the psychotic effects of various
      substances used in the experimental modeling of schizophrenia. Western blot
      analysis performed on samples from the rat cingulate, parietal, piriform cortices
      and also striatum revealed that antibody recognized one main band of
      approximately 40 kD, which corresponds to the predicted molecular weight of D4
      receptor protein. In immunocytochemical studies we found D4 receptor-positive
      neurons in all regions of prefrontal cortex (cingulate, agranular/insular and
      orbital cortices) and all cortical regions adjacent to prefrontal cortex, such as
      frontal, parietal and piriform cortex. Substantial number of D4 receptor-positive
      neurons has also been observed within the striatum and nucleus accumbens. In
      general, a clear stratification of the D4 receptor-positive neurons was observed
      in the cortex with the highest density seen in layers II/III and V/VI. D4
      immunopositive material was also found in the dendritic processes, particularly
      clearly visible in the layer II/III. At the cellular level D4 receptor
      immunoreactivity was seen predominantly on the periphery of the cell body, but a
      certain population of neurons with clear cytoplasmatic localization was also
      identified. In addition to cortical distribution of D4 receptor-positive neurons
      we tried also to define types of neurons expressing D4 receptor protein. In
      double-labeling experiments, D4 receptor protein was found in nonphosphorylated
      neurofilament H-positive, calbindin-D28k-positive, as well as parvalbumin
      positive cells. Since, used proteins are markers of certain populations of
      pyramidal neurons and GABA-ergic interneurons, respectively, our data indicate
      that D4 receptors are located on cortical pyramidal output neurons and their
      dendritic processes as well as on interneurons. Above localization indicates that
      D4 receptors are not only directly influencing excitability of cortical inter-
      and output neurons but also might be engaged in dendritic spatial and temporal
      integration, required for the generation of axonal messages. Additionally, our
      data show that D4 receptors are widely distributed throughout the cortex of rat
      brain, and that their cortical localization exceeds the localization of
      dopaminergic terminals.

PMID- 10898095
TI  - The influence of adrenal vein occlusion on whole-kidney hemodynamics in the
      spontaneously hypertensive rats.
AB  - It has been shown that occlusion of the adrenal vein causes an increase in renal
      vascular resistance in the ipsilateral kidney in Wistar Kyoto rats (WKY). The
      most probable mechanism of this phenomenon is the direct inflow of adrenal
      catecholamines to the kidney by the adrenal renal portal circulation (ARPC). As
      the number of vessels of the ARPC is bigger and the tonic sympathetic activity is
      higher in spontaneously hypertensive rats (SHR), the aim of the current study was
      to compare the effect of adrenal vein occlusion on renal vascular resistance
      between SHR and WKY. Mean arterial blood pressure and renal blood flow (RBF) were
      measured and renal vascular resistance (RVR) was calculated before and after
      closure of the adrenal vein. Occlusion of the adrenal vein significantly reduced
      RBF and increased RVR in both strains of rats. The rise of the RVR was
      significantly higher in SHR than in WKY. Therefore we assume that the hemodynamic
      responsiveness of the kidney due to increase in blood flow through ARPC is
      greater in SHR and may contribute to the development of arterial hypertension in
      this strain of rat.

PMID- 10898096
TI  - Cardiovascular effects of histamine administered intracerebroventricularly in
      critical haemorrhagic hypotension in rats.
AB  - The study was designed to determine the cardiovascular effects of histamine
      administered intracerebroventricularly (icv) in a rat model of volume-controlled
      haemorrhagic shock. The withdrawal of approximately 50% of total blood volume
      resulted in the death of all control saline icv treated animals within 30 min.
      Icv injection of histamine produced a prompt dose-dependent (0.1-100 nmol) and
      long-lasting (10-100 nmol) increase in mean arterial pressure (MAP), pulse
      pressure (PP) and heart rate (HR), with a 100% survival of 2h after treatment
      (100 nmol). The increase in MAP and HR after histamine administration in bled
      rats in comparison to the normovolaemic animals was 2.7-3.3- and 1.3-3.6-fold
      higher, respectively. Pretreatment with chlorpheniramine (50 nmol icv), H1
      receptor antagonist, inhibited the increase in MAP, PP, HR and survival rate
      produced by histamine, while chlorpheniramine given alone had no effect. Neither
      ranitidine (50 nmol icv), H2 histamine receptor antagonist, nor thioperamide (50
      nmol icv), H3 receptor blocker, influenced the histamine action, however, when
      given alone, both evoked the pressor effect with elongation of survival time. It
      can be concluded that histamine administered icv reverses the haemorrhagic shock
      conditions, and histamine H1 receptors are involved.

PMID- 10898097
TI  - Effect of endothelin-1 receptor antagonist BQ-123 on basilar artery diameter
      after subarachnoid hemorrhage (SAH) in rats.
AB  - Aim of the study was to quantify cerebral vasospasm in rats after subarachnoid
      hemorrhage (SAH) by morphometric examination of basilar artery and to evaluate
      the influence of endothelin receptor blocker BQ-123 on basilar artery
      constriction. The rat cisterna magna (CM) was cannulated and after 7 days SAH was
      developed by administration of 100 microl autologic, non-heparinized blood to the
      CM. The sham subarachnoid hemorrhage was developed by intracisternal
      administration of 100 microl of artificial cerebrospinal fluid. Endothelin
      receptor blocker BQ-123 was injected into the CM in a dose of 40 nmol diluted in
      50 microl of cerebrospinal fluid 20 min. before SAH, and 24h and 48 h after SAH.
      After perfusion fixation the brains were removed from the skull and histological
      preparations of basilar artery were done. The internal diameter and wall
      thickness of basilar arteries was measured by interactive morphometric method.
      The most severe vasospasm was found in rats after SAH. The presence of numerous
      infiltrations composed of neutrophils and macrophages correlated with advanced
      vasospasm (index of constriction 5 times lower than in normal), suggesting the
      role of other factors participating in the late phase of vasospasms after SAH.
      Administration of BQ-123 in the late phase after SAH caused the dilatation of
      basilar artery. Following the administration of BQ-123 in the late phase (48 h
      after SAH) the basilar artery dilated, its wall became thinner, and the number of
      leukocyte infiltrations in the subarachnoid space decreased compared to the
      values after SAH alone.

PMID- 10898098
TI  - A long-term fish diet modifies the toxic properties of human partially oxidized
      LDL on vascular preparations in vitro.
AB  - Both LDL oxidation and LDL fatty acid composition affect vascular relaxation and
      contraction. The aim of this study was to investigate whether long-lasting
      dietary habits (vegetarian, fish and high saturated fat as a control group) can
      change those properties of partially oxidized LDL (ox-LDL) which are reflected in
      altered vascular responses measured with a bioassay. The effects of ox-LDL were
      investigated on rat mesenteric arteries. In endothelium intact arterial rings the
      contractile responses to noradrenaline (NA) tended to be diminished in the
      presence of ox-LDL derived from the fish diet group compared with the other
      groups. In the endothelium denuded arterial rings the contractile responses to NA
      and KCl were significantly enhanced by ox-LDL from the fish diet group compared
      with the control group. The ox-LDL from the fish diet group increased the
      diclofenac, L-NAME resistant relaxations to ACh compared to the control diet
      group suggesting the role of endothelium derived hyperpolarizing factor (EDHF).
      In conclusion, partially oxidized LDL from subjects living on a fish diet is
      biologically more vasoactive in bioassay systems than partially oxidized LDL from
      those living on vegetarian or saturated fatty acid containing diets. The impaired
      responses in vasoconstriction and improved vasodilation seem to be endothelium
      dependent.

PMID- 10898099
TI  - Cardiovascular, metabolic and plasma catecholamine responses to passive and
      active exercises.
AB  - Eight healthy male volunteers (aged 19.6+/-3.0 years) were submitted to the
      unloaded active (AE) and passive (PE) cycling exercise-tests performed on an
      adapted cycle ergometer at a pedalling rate of 50 rpm. Intensity of active
      exercise was about 10% of VO2 max. In the PE exercise test the ergometer was
      moved electrically. During both tests the systolic time intervals (STI), stroke
      volume (SV), heart rate (HR), blood pressure (BP), oxygen uptake (VO2), rating of
      perceived exertion (RPE), electrical muscle activity (EMG), plasma adrenaline
      (A), noradrenaline (NE) and blood lactate (LA) concentrations were measured.
      Exercise induced changes in VO2, RPE and EMG were significantly higher during AE
      than PE. Shortening of the pre-ejection period (PEP) and diminishing of the PEP
      to ejection time (ET) ratio were similar in both types of exercise, whereas HR
      increased only during AE. A significant increase in cardiac output (p<0.01)
      resulted from increased SV (p<0.01) during PE and from increased HR (p <0.01)
      during AE. MAP increased only during PE and it was higher than at rest and during
      AE (p<0.01). Absence of changes in SV and MAP during AE may be considered as a
      secondary effect of the decrease in TPR. Plasma catecholamines did not increase
      above resting values in either type of exercise. Blood LA concentration increased
      during both PE and AE but it reached higher values (p<0.01) after the latter
      test. The present data suggest that the inotropic state depends on the
      mechanoreflexes originated in skeletal muscles. However, contribution of changes
      in preload to shortening of PEP can not be excluded.

PMID- 10898100
TI  - Effects of three-day bed rest on metabolic, hormonal and circulatory responses to
      an oral glucose load in endurance or strength trained athletes and untrained
      subjects.
AB  - The study was designed to find out (1) whether the effect of 3-day bed rest on
      blood glucose (BG) and plasma insulin (IRI) responses to glucose ingestion
      depends on preceding physical activity and (2) whether plasma adrenaline (A),
      noradrenaline (NA) and cardiovascular changes following a glucose load are
      modified by bed rest. Eleven sedentary students (22.5+/-0.3 yrs), 8 long distance
      runners (18.6+/-0.3 yrs) and 10 strength trained athletes (21.2+/-2.1 yrs) were
      examined before and after bed rest. Plasma IRI, BG, NA, A, heart rate (HR), and
      blood pressure (BP) were measured during 2 hrs following glucose (75 g)
      ingestion. The responses of BG and IRI to glucose load were calculated as
      incremental areas under the curves (auc). Both in athletes and untrained subjects
      bed rest markedly increased IRIauc, while BGauc was elevated only in sedentary
      subjects (p<0.05). The greatest increases in IRIauc and IRI/BG ratios were found
      in the endurance athletes. The data from all subjects (n = 29) revealed that the
      initial plasma NA and glucose-induced increases in NA and A were lowered after
      bed rest (p < 0.01). These effects were most pronounced in the endurance
      athletes. Bed rest did not influence HR or BP in any group. It is concluded that
      (1) the athletes have more adequate compensation for the bed-rest-induced
      decrement in insulin sensitivity than sedentary men; (2) three-day bed rest
      diminishes basal sympathetic activity and attenuates sympathoadrenal response to
      oral glucose; (3) endurance athletes have greater sympathetic inhibition than
      strength athletes or sedentary men.

PMID- 10898101
TI  - Relationship between the tension-time area and the frequency of stimulation in
      motor units of the rat medial gastrocnemius muscle.
AB  - The tension-time area is an estimation of the work performed by contracting motor
      units. The relationship between tension and frequency of stimulation and between
      tension-time area and frequency have been studied on 148 single motor units of
      the rat medial gastrocnemius muscle, under isometric conditions. Motor units were
      classified as fast fatigable (FF), fast resistant to fatigue (FR) or slow (S).
      Trains of stimuli of increasing frequency and constant duration were used. For
      all motor units a half of the maximum tetanic tension corresponded to lower
      frequencies compared to frequencies at a half of the maximum tension-time area.
      Moreover, the slopes of tension-frequency and area-frequency curves (change of
      tension or area per 1 Hz rise in frequency) were higher for slow than for fast
      motor units. The tension-time area per one pulse was calculated for different
      frequencies of stimulation. For slow units the maximum area per pulse
      corresponded to significantly lower frequencies than for fast ones, especially of
      FF type. However, for all three types of motor units this optimal frequency
      corresponded to sub-fused tetani with a tension of about 75% of the maximum
      tension, and with the fusion index slightly over 0.90. The absolute values of the
      maximum tension-time area per pulse revealed that in one contraction within the
      tetanus, slow units are generating greater work than FR units. The work performed
      by FF units is nearly two times larger than for S units, although the tension of
      slow units is over eight times lower. The presented results reveal that the
      contraction of slow motor units is much more effective than was suggested based
      on their low tension.

PMID- 10898102
TI  - Dissociation of parathyroid hormone and cyclic-3', 5'AMP effects on Na-Pi uptake
      by cells isolated from proximal straight tubules of rat kidney.
AB  - Studies in respiratory alkalotic or short-term phosphate deprived rats raised the
      possibility that in straight portion of proximal tubules (PST) cAMP might be not
      a mediator of PTH in inhibition of phosphate reabsorption. The present
      experiments directly compared the sensitivity of Na-dependent phosphate [32P] (Na
      Pi) uptake to PTH or cAMP by PCT or PST cells freshly prepared from outer cortex
      and outer stripe of outer medulla of rat kidney. The purity of the cells was
      examined by activity of enzymes specific for PST i.e. glutamine synthetase, gamma
      glutamyl transpeptidase and creatine kinase, a marker enzyme for medullary thick
      ascending limb (MTAL) and distal convoluted tubule. Similar inhibition of Na-Pi
      uptake by 1-34 bPTH by PST and PCT cells was observed: -33.0 and -30.0% (ns),
      respectively. In contrast, dibutyryl cAMP decreased Na-Pi uptake only by PCT but
      not by PST cells: -31.0 and -3.6% (p<0.02), respectively. The 3-isobutyl-1
      methylxanthine (IBMX), a phosphodiesterase inhibitor, resulted in slight
      stimulation of Na-Pi uptake by PST but strong inhibition by PCT cells: 7.8 vs 
      26.0% (p<0.001). In contrast to PCT in PST cells cAMP seems to play a minor role
      as a mediator of inhibition of Na-Pi uptake by PTH.

PMID- 10898103
TI  - The effects of ammonia on pancreatic enzyme secretion in vivo and in vitro.
AB  - BACKGROUND: Recent studies clearly demonstrate that Helicobacter pylori (H.
      pylori) infection of the stomach causes persistent elevation of ammonia (NH3) in
      gastric juice leading to hypergastrinemia and enhanced pancreatic enzyme
      secretion. METHODS: The aim of this study is to evaluate the influence of NH4OH
      on plasma gastrin level and exocrine pancreatic secretion in vivo in conscious
      dogs equipped with chronic pancreatic fistulas and on secretory activity of in
      vitro isolated acini obtained from the rat pancreas by collagenase digestion. The
      effects of NH4OH on amylase release from pancreatic acini were compared with
      those produced by simple alkalization of these acini with NaOH. RESULTS: NH4OH
      given intraduodenally (i.d.) in increasing concentrations (0.5, 1.0, 2.0, 4.0, or
      8.0 mM/L) resulted in an increase of pancreatic protein output, reaching
      respectively 9%, 10%, 19%, 16% and 17% of caerulein maximum in these animals and
      in a marked increase in plasma gastrin level. NH4OH (8 x 0 mM/L, i.d.) given
      during intravenous (i.v.) infusion of secretin (50 pmol/kg-h) and cholecystokinin
      (50 pmol/kg-h) reduced the HCO3 and protein outputs by 35% and 37% respectively,
      as compared to control obtained with infusion of secretin plus cholecystokinin
      alone. When pancreatic secretion was stimulated by ordinary feeding the same
      amount of NH4OH administered i.d. decreased the HCO3- and protein responses by
      78% and 47% respectively, and had no significant effect on postprandial plasma
      gastrin. In isolated pancreatic acini, increasing concentrations of NH4OH (10(-7)
      10(-4) M) produced a concentration-dependent stimulation of amylase release,
      reaching about 43% of caerulein-induced maximum. When various concentrations of
      NH4OH were added to submaximal concentration of caerulein (10(-12) M) or
      urecholine (10(-5) M), the enzyme secretion was reduced at a dose 10(-5) M of
      NH4OH by 38% or 40%, respectively. Simple alkalization with NaOH of the
      incubation medium up to pH 8.5 markedly stimulated basal amylase secretion from
      isolated pancreatic acini, whereas the secretory response of these acini to
      pancreatic secretagogues was significantly diminished by about 30%. LDH release
      into the incubation medium was not significantly changed in all tests indicating
      that NH4OH did not produce any apparent damage of pancreatic acini and this was
      confirmed by histological examination of these acini. CONCLUSIONS: 1. NH4OH
      affects basal and stimulated pancreatic secretion. 2. The excessive release of
      gastrin may be responsible for the stimulation of basal pancreatic enzyme
      secretion in conscious animals, and 3. The inhibitory effects of NH4OH on
      stimulated secretion might be mediated, at least in part, by its direct action on
      the isolated pancreatic acini possibly due to the alkalization of these acini.

PMID- 10898104
TI  - Experimental inflammatory bowel disease--role of T cells.
AB  - BACKGROUND: Our experiments were aimed to test: 1. which lymphocyte
      subpopulations participate in mouse colitis, produced by intrarectal (i.r.)
      deposition of trinitrobenzene sulphonic acid (TNBSA, TNP hapten); 2. the
      expression of cell adhesion molecules on lymphocytes draining the site of
      reaction; 3. the influence of mouse haplotype on the development of colitis.
      METHODS: CBA/J, BALB/c and C57BI/6 inbred and outbred Swiss Webster strains were
      used. Mesentheric lymph node (MLN) cells of immunized animals, unseparated or
      separated into CD4+, CD8+ or gammadelta+ and alphabeta+ T cell subpopulations or
      depleted of B lymphocytes, were transferred into recipients which were challenged
      i.r. with TNBSA. Inflammatory reaction in the colon was confirmed macro- and
      microscopically and by myeloperoxidase (MPO) level. MLN lymphocyte surface
      markers were tested cytofluorimetrically using appropriate antibodies. RESULTS:
      Sensitization with TNP results in chronic colitis (hapten dose-dependent colon
      weight gain and cellular infiltrate, significant increase of MPO level) only in
      CBA/J and BALB/c strains and can be adoptively transferred in a cell-dose
      dependent manner into syngeneic recipients by T alphabeta+ cells of both CD4+ and
      CD8+ subpopulations. T gammadelta+ cells were ineffective and B lymphocytes do
      not participate in the passive transfer reaction. In MLN the number of T
      lymphocytes positive for cell adhesion molecules particularly LPAM-1 (V-CAM1) and
      LPAM-2 increases significantly. CONCLUSIONS: Both CD4+ and CD8+ lymphocytes
      participate in the development of TNP-induced colitis. High MPO level may
      suggests that both Th1 and Th2 cells are involved. Colitis is accompanied by a
      significant accumulation in MLN of T lymphocytes positive for several cell
      surface adhesion molecules characteristic for memory T cells. Significant
      differences in susceptibility to develop colitis were found between different
      strains of mice.

PMID- 10898105
TI  - The influence of indomethacin on the acth secretion induced by central
      stimulation of adrenergic receptors.
AB  - We had previously demonstrated that indomethacin affected the corticosterone
      secretion induced by central stimulation of alpha-but not beta-adrenergic
      receptors in conscious rats. In the present study we investigated whether
      hypothalamic and/or pituitary prostaglandins (PGs) were involved in the central
      adrenergic stimulation of ACTH secretion. Indomethacin, 2 mg/kg ip or 10 microg
      intracerebroventricularly (icv), was administered 15 min before phenylephrine (30
      microg icv), an alpha-adrenergic agonist, clonidine (10 microg), an alpha2
      adrenergic agonist, and isoprenaline (20 microg) or clenbuterol (10 microg), a
      beta1- or beta2-adrenergic agonist. One hour after the last injection the rats
      were decapitated and plasma levels of ACTH were measured. The present results
      show that the ACTH responses induced by icv administration of phenylephrine and
      clonidine were considerably impaired by icv or ip pretreatment with indomethacin,
      an inhibitor of prostaglandin synthesis. Indomethacin given by either route only
      slightly diminished the isoprenaline-induced ACTH response and did not
      substantially alter the clenbuterol-induced response. The adrenergic-induced ACTH
      responses were more potently inhibited by ip than by icv pretreatment with
      indomethacin, which may result from a stronger inhibition of PGs synthesis in the
      median eminence and anterior pituitary by ip pretreatment with indomethacin than
      in hypothalamic structures by its icv administration. These results indicate a
      significant involvement of PGs in central stimulation of the hypothalamic
      pituitary adrenal (HPA) axis by alpha1- and alpha2- but not beta-adrenergic
      receptors.

PMID- 10898106
TI  - Gene expression and peptide localization for LH/hCG receptor in porcine small and
      large luteal cells: possible regulation by opioid peptides.
AB  - The aim of the present studies was to investigate (1) the presence of LH receptor
      (LHR) in porcine separated small (SLCs) and large (LLCs) luteal cells taken from
      mid-luteal corpora lutea and (2) the influence of opioid agonist, FK 33-824 (FK)
      on LHR gene expression in these cells. Immunocytochemistry revealed intense
      staining for LHR in both SLCs and LLCs. Reverse transcription-polymerase chain
      reaction (RT-PCR) and Southern hybridization were used to check the effect of FK
      and hCG on LHR gene expression. The LHR gene expression was observed in non
      stimulated LLCs and in both types of cells after treatment with FK or hCG. FK
      stimulated LHR gene expression in SLCs and inhibited the gene expression in LLCs.
      Moreover, FK inhibited and potentiated stimulatory influence of hCG on the gene
      expression in LLCs and SLCs, respectively. These results suggest that LHR gene
      expression in porcine luteal cells can be regulated by opioid peptides.

PMID- 10898107
TI  - Evaluation of the genetic component of variability in CYP3A4 activity: a repeated
      drug administration method.
AB  - The CYP3A4 enzyme contributes to the disposition of more than 60 therapeutically
      important drugs and displays marked person-to-person variability of the catalytic
      function. However, the extent of genetic contribution to variability in CYP3A4
      activity remains elusive. Recently, we showed that a comparison of between-
      (SDb2) and within-person (SDW2) variances provides an estimate of the genetic
      component of variability in drug disposition. The aim of the present analysis was
      to assess the genetic control of CYP3A4 activity in vivo. A computerized
      literature search was conducted covering 1966 to September 1999 to identify
      studies reporting repeated administration of CYP3A4 substrates. The genetic
      contribution (rGC) to disposition of each CYP3A4 substrate was obtained by the
      formula (SDb2-SDW2)/SDb2. The rGC values approaching 1.0, point to overwhelming
      genetic control, whereas those close to zero suggest that environmental factors
      dominate. A total of 16 studies with 10 different CYP3A4 substrates were
      identified (n = 161 subjects). The rGC for hepatic CYP3A4 activity as measured by
      midazolam plasma clearance or the erythromycin breath test was 0.96 (0.92-0.98)
      (95% Cl) and 0.89 (0.65-0.98), respectively (P < 0.05). The point estimates of
      rGC for composite (hepatic + intestinal) CYP3A4 activity measured after oral
      administration of cyclosporine, ethinylestradiol, ethylmorphine, nifedipine and
      nitrendipine, ranged from 0.66-0.98 (median: 0.83) (P < 0.05). Cyclosporine data
      suggested a higher genetic control of CYP3A4 at night than during the day. These
      data indicate that further molecular genetic investigations are warranted to
      identify genetic variants at CYP3A4 or elsewhere in the genome which contribute
      to regulation of CYP3A4 activity.

PMID- 10898108
TI  - Characterization of two highly polymorphic human tryptase loci and comparison
      with a newly discovered monkey tryptase ortholog.
AB  - Tryptases are serine proteases involved in mast cell-mediated inflammatory
      responses which represent potential targets of drugs against diseases such as
      asthma, arthritis and inflammatory bowel disease. In order to interpret
      pharmacodynamic data on the tryptase inhibitors undergoing clinical trials, we
      defined the genetic variability of the tryptase 1 (TPS1) and tryptase 2 (TPS2)
      loci by screening a reference population of 32 individuals representing three
      major ethnic groups (Caucasian, African American, Asian). Using overlapping PCR
      products, we resequenced the entire tryptase genes with the only exclusion of
      TPS2 intron 1 and 20 bp of TPS2 5' untranslated region included in exon 1 and we
      identified 21 novel single nucleotide polymorphisms in TPS1 and 17 single
      nucleotide polymorphisms plus a large polymorphic deletion in the TPS2 gene. We
      also compared the type, frequency and distribution of single nucleotide
      polymorphisms in TPS1 and TPS2 and we observed that the polymorphism frequency
      within these two loci is unexpectedly high (approximately 1 SNP every 90 bp) and
      that some of the allele frequencies differ significantly among the three ethnic
      groups. Based on differences observed in preclinical studies using a cynomolgus
      monkey (Macaca fascicularis) asthma model system, we investigated the difference
      between monkey and human tryptase genes in order to better understand the
      mechanism of action of our tryptase inhibitors.

PMID- 10898109
TI  - Pharmacological properties of naturally occurring variants of the human
      norepinephrine transporter.
AB  - The human norepinephrine transporter (hNET) gene has five sequence polymorphisms
      that predict amino acid substitutions in the transporter protein: Val69Ile,
      Thr99Ile, Val245Ile, Val449Ile, and Gly478Ser. In order to functionally
      characterize the naturally occurring transporter variants, we used site-directed
      mutagenesis to establish the hNET variants and compared some basic
      pharmacological properties (uptake of norepinephrine and its inhibition by the
      tricyclic antidepressant desipramine) in COS-7 cells transiently expressing
      variant hNETs and wild-type hNET. None of the hNET variants displayed changes in
      the potency (Ki) of desipramine for inhibition of norepinephrine uptake.
      Furthermore, variants Val69Ile, Thr99Ile, ValZ45Ile, and Val449Ile did not affect
      kinetic constants (Km, Vmax) of norepinephrine uptake. However, COS-7 cells
      expressing the hNET variant Gly478Ser displayed an approximately four-fold
      increase in the Km for norepinephrine, while the Vmax was unaffected. The
      increase in the Km, which is equivalent to a four-fold reduction in the affinity
      of the variant hNET for its natural substrate norepinephrine, indicates that the
      glycine in position 478 is part of a substrate recognition domain. The reduced
      clearance of released norepinephrine by reuptake through the Gly478Ser variant
      might cause an increase in the synaptic and the circulating concentration of
      norepinephrine. Elevated norepinephrine concentrations have been associated with
      human diseases and it will be interesting to explore a possible contribution by
      the Gly478Ser variant to certain disease states.

PMID- 10898110
TI  - Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase
      type II.
AB  - Human prostatic steroid 5alpha-reductase, encoded by the SRD5A2 gene on
      chromosome band 2p23, catalyses the irreversible conversion of testosterone to
      dihydrotestosterone (DHT), the most active androgen in the prostate, with NADPH
      as its cofactor. This enzyme has never been purified but a number of competitive
      inhibitors have been developed for this enzyme since increased steroid 5alpha
      reductase activity may cause benign prostatic hypertrophy and prostate cancer. We
      report here the detailed biochemical and pharmacogenetic dissection of the human
      enzyme by analysing 10 missense substitutions and three double mutants which are
      all naturally found in humans. Nine of these 13 mutants reduce activity (measured
      as Vmax) by 20% or more, three increase steroid 5alpha-reductase by more than 15%
      and one results in essentially unaltered kinetic properties suggesting that it is
      a truly neutral ('polymorphic') amino acid substitution. Substantial
      pharmacogenetic variation among the mutants was also observed when three
      competitive inhibitors, finasteride, GG745 (dutasteride) and PNU157706, were
      investigated. Our studies not only define the substrate and cofactor binding
      sites of human steroid 5alpha-reductase, but also have significant consequences
      for the pharmacological usage of steroid 5alpha-reductase inhibitors in human
      patients treated for prostatic conditions.

PMID- 10898111
TI  - Two linked mutations in transcriptional regulatory elements of the CYP3A5 gene
      constitute the major genetic determinant of polymorphic activity in humans.
AB  - Cytochrome P450 3A subfamily members (CYP3A) are the most abundant liver
      cytochrome P450 forms, responsible for the biotransformation of over 50% of all
      drugs. The expression and activity of isoforms CYP3A4 and CYP3A5 show wide inter
      individual variation, influencing both drug response and disease susceptibility.
      The molecular basis for this variation has never been defined. In this study, we
      used midazolam to characterize CYP3A5 phenotype in a panel of liver samples. A
      clear bimodality in metabolism was observed. Analysis of the 5' flanking region
      of the CYP3A5 gene identified two linked polymorphisms, T-369G and A-45G, located
      in transcriptional regulatory elements which are associated with increased
      expression and activity of the gene. A polymerase chain reaction based detection
      assay is described facilitating future studies into both the metabolic
      consequences of this variation and disease association studies relating to
      CYP3A5.

PMID- 10898112
TI  - Effect of gender, sex hormones, time variables and physiological urinary pH on
      apparent CYP2D6 activity as assessed by metabolic ratios of marker substrates.
AB  - The effects of gender, time variables, menstrual cycle phases, plasma sex hormone
      concentrations and physiologic urinary pH on CYP2D6 phenotyping were studied
      using two widely employed CYP2D6 probe drugs, namely dextromethorphan and
      metoprolol. Phenotyping on a single occasion of 150 young, healthy, drug-free
      women and men revealed that the dextromethorphan: dextrorphan metabolic ratio
      (MR) was significantly lower (P < 0.0001) in 56 female extensive metabolizers
      (0.008+/-0.021) compared to 86 male extensive metabolizers (0.020 +/-0.040).
      Urinary pH was a significant predictor of dextromethorphan: dextrorphan MRs in
      men and women (P < 0.001). Once-a-month phenotyping with dextromethorphan of 12
      healthy young men (eight extensive metabolizers and four poor metabolizers) over
      a 1-year period, as well as every-other-day phenotyping with dextromethorphan of
      healthy, pre-menopausal women (10 extensive metabolizers and 2 poor metabolizers)
      during a complete menstrual cycle, did not follow a particular pattern and showed
      similar intrasubject variability ranging from 24.1% to 74.5% (mean 50.9%) in men
      and from 20.5% to 96.2% (mean 52.0%) in women, independent of the CYP2D6
      phenotype (P = 0.342). Using metoprolol as a probe drug, considerable
      intrasubject variability (38.6+/- 12.0%) but no correlation between metoprolol:
      alpha-hydroxymetoprolol MRs and pre-ovulatory, ovulatory and luteal phases (mean
      +/- SD metoprolol: a-hydroxymetoprolol MRs: 1.086+/- 1.137 pre-ovulatory; 1.159+/
      1.158 ovulatory and 1.002+/-1.405 luteal phase; P> 0.9) or 17beta-oestradiol,
      progesterone or testosterone plasma concentrations was observed. There was a
      significant inverse relationship between physiologic urinary pH and sequential
      dextromethorphan: dextrorphan MRs as well as metoprolol: alpha-hydroxymetoprolol
      MRs in men and women, with metabolic ratios varying up to six-fold with
      metoprolol and up to 20-fold with dextromethorphan (ANCOVA P < 0.001). We
      conclude that apparent CYP2D6 activity is highly variable, independent of
      menstrual cycle phases, sex hormones, time variables or phenotype. Up to 80% of
      the observed variability can be explained by variations of urinary pH within the
      physiological range. An apparent phenotype shift as a result of variations in
      urinary pH may be observed in individuals who have metabolic ratios close to the
      population antimode.

PMID- 10898113
TI  - A novel mutation in the flavin-containing monooxygenase 3 gene, FM03, that causes
      fish-odour syndrome: activity of the mutant enzyme assessed by proton NMR
      spectroscopy.
AB  - We have previously shown that primary trimethylaminuria, or fish-odour syndrome,
      is caused by an inherited defect in the flavin-containing monooxygenase 3 (FMO3)
      catalysed N-oxidation of the dietary-derived malodorous amine, trimethylamine
      (TMA). We now report a novel causative mutation for the disorder identified in a
      young girl diagnosed by proton nuclear magnetic resonance (NMR) spectroscopy of
      her urine. Sequence analysis of genomic DNA amplified from the patient revealed
      that she was homozygous for a T to C missense mutation in exon 3 of the FMO3
      gene. The mutation changes an ATG triplet, encoding methionine, at codon 82 to an
      ACG triplet, encoding threonine. A polymerase chain reaction/restriction enzyme
      based assay was devised to genotype individuals for the FMO3Thr82 allele. Wild
      type and mutant FMO3, heterologously expressed in a baculovirus-insect cell
      system, were assayed by ultraviolet spectrophotometry and NMR spectroscopy for
      their ability to catalyse the N-oxidation of TMA. The latter technique has the
      advantage of enabling the simultaneous, direct and semi-continuous measurement of
      both of the products, TMA N-oxide and NADP, and of one of the reactants, NADPH.
      Results obtained from both techniques demonstrate that the Met82Thr mutation
      abolishes the catalytic activity of the enzyme and thus represents the genetic
      basis of the disorder in this individual. The combination of NMR spectroscopy
      with gene sequence and expression technology provides a powerful means of
      determining genotype-phenotype relationships in trimethylaminuria.

PMID- 10898114
TI  - Analysis of paraoxonase (PON1) L55M status requires both genotype and phenotype.
AB  - Paraoxonase (PON1) is tightly associated with high-density lipoprotein particles
      and is believed to contribute to the prevention of atherosclerosis by
      metabolizing oxidized lipids. PON1 also hydrolyses the bioactive oxon forms of
      organophosphorus pesticides such as parathion, diazinon and chlorpyrifos. Two
      common polymorphisms have been identified in the coding sequence of human PON1:
      L55M and R192Q. Several previous studies have found that the presence of the
      PON1R192 allele raises the risk of cardiovascular disease while others found no
      correlation. The studies, however, have focused on the genotype of PON1 and not
      the expression level of the protein. We found that the PON1 expression level in
      plasma, as determined by the rates of paraoxon and diazoxon hydrolysis, varies
      widely among individuals and within a genotype. Previous studies found that
      individuals having Met at PON155 have lower levels of both PON1 mRNA and
      activity. In this study, we determined the plasma activity levels of PON1 and
      examined the relationships between PON155 genotype and PON1 level. As with
      PON1192, we found considerable overlap in activity among the PON155 genotypes. Of
      the 317 individuals whose PON1 status was determined in this study, 48.9% were
      PON1Q192 homozygotes. Analysis of the PON1QQ192 population showed that while the
      average PON1 activity (diazoxon hydrolysis) was 12266 U/L for PON1LL55 and 7777
      U/L for PON1MM55, a given PONMM55 individual could have more than twice the
      activity of a PON1LL55 individual. PON1 status, which includes PON1 level as well
      as PON1192 genotype, may be a better predictor for cardiovascular disease or
      organophosphate susceptibility than PON1 genotype alone.

PMID- 10898115
TI  - Breast cancer, passive and active cigarette smoking and N-acetyltransferase 2
      genotype.
AB  - The relationship of breast cancer to cigarette smoking is inconsistent in the
      literature, possibly due in part to heterogeneity in carcinogen metabolism. N
      acetyltransferase 2 (NAT2) enzyme activity is believed to play a role in the
      activation of tobacco smoke carcinogens. We examined the effect of NAT2 genetic
      polymorphisms on risk of breast cancer from active and passive smoking. Women
      were recruited from those who had suspicious breast masses detected clinically
      and/or mammographically. Questionnaire data were collected prior to biopsy
      diagnosis to blind subjects and interviewers. Histopathology showed 113 cases
      with mammary carcinoma (30 carcinoma in situ) and 278 controls with benign breast
      disease. NAT2 genotype was determined using allele-specific polymerase chain
      reaction amplification to detect slow acetylator mutations. Effects of passive
      and active tobacco smoke and of NAT2 genotype on breast cancer risk were examined
      with logistic regression controlling for known risk factors. Models first
      included all controls, and subsequently 107 with no or low risk (normal breast or
      no hyperplasia), and finally 148 with high risk (hyperplasia, atypical
      hyperplasia, complex fibroadenomas). Referents had no active or passive smoke
      exposure. We found no association between breast cancer risk and NAT2, smoking
      status (never, former, current), smoking duration, or cigarettes per day. There
      were no effects of passive exposure among never-smokers. Models were unchanged
      across control groups. There were no statistical interactions between tobacco
      smoke exposure and NAT2. The results were similar when restricting the analysis
      to invasive cancers. These findings do not support the hypothesis that NAT2 is a
      risk factor for breast cancer or that it alters susceptibility to tobacco smoke.

PMID- 10898116
TI  - Predominant influence of the 3'-region of dopamine D2 receptor gene (DRD2) on the
      clinical phenotype in German alcoholics.

PMID- 10898117
TI  - Genetic polymorphisms in glutathione S-transferase M1 and T1 in an Australian
      Aborigine population.

PMID- 10898119
TI  - Cetirizine and loratadine: a comparison using the ED50 in skin reactions.
AB  - To quantify objectively the comparative potencies of the antihistamines,
      loratadine and cetirizine, we determined the dose that inhibits histamine-induced
      skin reactions by 50% of the maximum response (ED50) for each drug. Cetirizine at
      2.5, 5 or 10 mg, loratadine at 10, 20 or 40 mg or placebo were given to 14
      healthy female subjects in a randomized double-blind crossover design. Inhibition
      of the wheal and flare response to the histamine prick test (10, 100 and 500
      mg/ml) was evaluated. Depending on the histamine concentrations, the ED50s for
      wheals were in the ranges 4.3 - 4.7, 2.1 - 2.2 and 1.7 - 1.9 mg cetirizine, 2, 4
      and 6 h after dosing, respectively. For loratadine, the ED50 for wheals were in
      the ranges 35.6 - > 40, 9.1 - 24.1 and 9.1 - 13.9 mg, 2, 4 and 6 h after dosing,
      respectively. Calculation of the ED50 demonstrated that, on average, cetirizine
      is seven to nine times more potent than loratadine at inhibiting wheal and flare
      reactions.

PMID- 10898118
TI  - Efficacy and safety of cerivastatin 0.8 mg in patients with
      hypercholesterolaemia: the pivotal placebo-controlled clinical trial.
      Cerivastatin Study Group.
AB  - This pivotal, multicentre, double-blind, parallel-group study evaluated the
      efficacy and safety of cerivastatin 0.8 mg. Patients with primary
      hypercholesterolaemia were randomized, after 10 weeks' dietary stabilization on
      an American Heart Association (AHA) Step I diet, to treatment with cerivastatin
      0.8 mg (n = 776), cerivastatin 0.4 mg (n = 195) or placebo (n = 199) once daily
      for 8 weeks. Cerivastatin 0.8 mg reduced mean low density lipoprotein-cholesterol
      (LDL-C) by 41.8% compared with cerivastatin 0.4 mg (-35.6%, P < 0.0001) or
      placebo. In 90% of patients receiving cerivastatin 0.8 mg LDL-C was reduced by
      23.9 -58.4% (6th - 95th percentile). Overall attainment of the National
      Cholesterol Education Program (NCEP) goal was achieved by 84% of patients
      receiving cerivastatin 0.8 mg and by 59% of those with coronary heart disease
      (CHD). In the sub-population meeting the NCEP criteria for pharmacological
      therapy for LDL-C reduction, 74.6% of patients, including the 59% with CHD,
      reached the goal with cerivastatin 0.8 mg. Cerivastatin 0.8 mg also reduced mean
      total cholesterol by 29.9%, apolipoprotein B by 33.2% and median triglycerides by
      22.9% (all P < 0.0001). Mean high density lipoprotein-cholesterol (HDL-C) and
      apolipoprotein A1 were elevated 8.7% (P < 0.0001) and 4.5% (P < 0.0001),
      respectively, by cerivastatin 0.8 mg. Reductions of triglyceride and elevation in
      HDL-C were dependent upon triglyceride baseline levels; in patients having
      baseline triglyceride levels 250 - 400 mg/dl, cerivastatin 0.8 mg reduced median
      triglycerides by 29.5% and elevated HDL-C by 13.2%. Cerivastatin 0.8 mg was well
      tolerated. The most commonly reported adverse events included headache,
      pharyngitis and rhinitis (4 - 6%). Symptomatic creatine kinase elevations > 10
      times upper limit of normal occurred in 0%, 1% and 0.9% of patients receiving
      placebo, cerivastatin 0.4 mg or cerivastatin 0.8 mg, respectively. Cerivastatin
      0.8 mg is an effective and safe treatment for patients with primary
      hypercholesterolaemia who need aggressive LDL-C lowering in order to achieve NCEP
      recommended levels.

PMID- 10898120
TI  - Expression of CD44 variants in lung cancer and its relationship to hyaluronan
      binding.
AB  - We examined the expression of CD44 variant forms and their binding to hyaluronan
      (HA) in lung cancer cell lines. There was no relationship between the level of
      expression of CD44 variants and HA binding in different lung cancer cell lines.
      The expression of CD44v6 and CD44E in some cell lines was not always associated
      with HA binding. There was no relationship between the tissue pathological type
      and CD44 expression or HA binding. Deglycosylation by neuraminidase induced CD44
      HA binding in human lung cancer cell lines. Our findings suggest that the HA
      binding ability of CD44, which is negatively regulated by glycosylation, might be
      a more important factor in tumorigenesis or metastasis than the expression of
      CD44 variant forms.

PMID- 10898122
TI  - Streptozotocin-induced diabetic hyperglycaemia produces more EEG activity than
      normoglycaemia and hypoglycaemia during and after anoxia loading in rats.
AB  - The brain requires oxygen and glucose for energy metabolism. Electroencephalogram
      (EEG) was recorded to determine the effect of glucose concentration on the
      cerebral function in hypoxic episode. Rats were divided into 3 groups: a
      streptozotocin-induced diabetic hyperglycaemic group, a normoglycaemic group, and
      an insulin-induced hypoglycaemic group. Hypoxia was induced by ventilating with
      100% N2 for 3 min. EEG amplitude both 5 and 10 min after anoxia loading was
      higher in the diabetic hyperglycaemic than in the normoglycaemic group, though
      not significantly. Time for decreasing the EEG amplitude during anoxia loading
      was significantly longer in the hyperglycaemic than in the normoglycaemic group.
      Time for recovering the EEG amplitude after anoxia loading was significantly
      shorter in the hyperglycaemic group and was longer, though not significantly, in
      the hypoglycaemic group than in the normoglycaemic one. These results suggest the
      brain is more tolerant to hypoxia during diabetic hyperglycaemia than during
      normoglycaemia.

PMID- 10898121
TI  - Amtolmetin guacyl versus piroxicam in patients with osteoarthritis.
AB  - The efficacy and tolerability of amtolmetin guacyl (AMG), a new non-steroidal
      anti-inflammatory drug, were compared with piroxicam, in patients with
      osteoarthritis. In a randomized double-blind study patients with arthritis (n =
      99) received either 600 mg AMG on an empty stomach or 20 mg of piroxicam on a
      full stomach, once daily for 30 days. All clinical parameters improved
      significantly with both drugs; there were no significant differences between the
      two treatments. Tolerability, assessed by the patients, was significantly better
      in the AMG group. In the piroxicam group nine of 50 patients withdrew because of
      side-effects (gastrointestinal) compared with two of 49 (nausea and headache) in
      the AMG group. There were three cases of perforation, ulcer and bleeding in the
      piroxicam group but no serious side-effects with AMG. Total numbers of side
      effects were similar in the two groups, but epigastric and abdominal pain were
      more frequent and more intense with piroxicam. AMG was as effective as piroxicam
      in controlling the symptoms of osteoarthritis, but showed better gastrointestinal
      tolerability.

PMID- 10898123
TI  - Incidence in young adulthood-onset Type 1 diabetes mellitus in Lithuania during
      1991-1997. Lithuanian Epidemiology Diabetes Study Group.
AB  - Our aim was to determine the incidence of Type 1 diabetes mellitus (T1DM) in the
      15-39-yr-old Lithuanian population from 1991 to 1997. A specifically developed
      communications system with all endocrinologists/diabetologists and general
      practitioners involved in diabetes care covering 100% of the sample Lithuanian
      population was the initial data source. Annual reports from regional
      endocrinologists/diabetologists, death certificates and patients' lists from
      Diabetes Societies remained as secondary sources for case ascertainment. The
      annual incidence was calculated per 100,000 persons/yr. The trend in incidence
      was estimated by fitting the linear regression model with the annual incidence
      data. The total of 769 new cases (496 males and 273 females) of T1DM were
      recorded among the 15-39-yr-old population during the period 1 January 1991-31
      December 1997. The average age-standardised incidence rate was 7.78 per 100,000
      persons/yr [95% Poisson distribution confidence interval (CI) 7.25-8.35] and was
      slightly higher among males (9.68 per 100,000 persons/yr, 95% CI 8.87-10.57) than
      among females (5.71 per 100,000, 95% CI 5.07-6.43). Male/female ratio was 1.82
      (95% CI 1.69-1.95). Results of the linear regression model showed that the
      incidence of T1DM in the 15-39-yr-old population had a tendency to increase. The
      incidence data of T1DM in Lithuania are appropriate to those in Poland and lower
      than in other countries of the Baltic Sea region.

PMID- 10898124
TI  - Aldose reductase mRNA expression is associated with rapid development of diabetic
      microangiopathy in Japanese Type 2 diabetic (T2DM) patients.
AB  - There appears to be an obvious difference in the susceptibility to diabetic
      microangiopathy among Type 2 diabetic (T2DM) patients. We examined the hypothesis
      that aldose reductase (AR) messenger ribonucleic acid (mRNA) expression may be
      enhanced in diabetic patients susceptible to diabetic microangiopathy by
      measuring AR mRNA expression in the polymorphonuclear leukocytes (PMNs) obtained
      from T2DM patients. The AR mRNA and beta-actin mRNA expressions were measured by
      reverse transcription-polymerase chain reaction method. The relative AR mRNA
      expression to beta-actin mRNA expression significantly increased in the PMNs of
      T2DM patients, compared to normal healthy controls. The relative AR mRNA
      expression tended to increase with an increase of glycosylated haemoglobin A1c
      (HbA1c) levels. The patients who showed both progressive diabetic retinopathy and
      diabetic neuropathy within 10 years after the diagnosis of T2DM (Group I) showed
      significantly 1.6 times higher AR mRNA expressions than those who have not shown
      both complications over 10 years after diagnosis (Group II), in spite of no
      obvious difference in glycaemic control between both groups. The present data
      indicate that the AR mRNA expression increased in the PMNs of T2DM patients and
      there is an obvious difference in the PMNs AR mRNA expression between T2DM
      patients susceptible and relatively resistant to the development of diabetic
      microangiopathy.

PMID- 10898125
TI  - Effect of sleep deprivation on insulin sensitivity and cortisol concentration in
      healthy subjects.
AB  - The objective of this study was to assess insulin sensitivity and cortisol
      concentration in healthy subjects with 24-hr sleep deprivation. A randomised,
      single-blind, controlled clinical trial was performed in 28 healthy subjects.
      Fourteen individuals were studied before and after 24-hr sleep deprivation and 14
      volunteers with normal sleep periods (NSP) as a control group. Serum creatinine,
      uric acid, total cholesterol, high-density lipoprotein cholesterol, and
      triglyceride concentrations were measured in both groups. Insulin suppression
      test modified with octreotide (IST) and cortisol levels were performed before and
      after 24-hr sleep deprivation or NSP. Clinical and metabolic characteristics of
      the subjects in both groups are similar. Steady-state glucose (SSG) concentration
      of the IST was significantly higher after 24-hr sleep deprivation (5.7+/-2.1 vs
      6.7+/-2.2 mmol/l; p=0.01). SSG level was similar before and after NSP (5.0+/-2.1
      vs 5.0+/-1.8 mmol/l, respectively; p=0.91). There were not significant
      differences in cortisol levels between initial and final tests in both groups. In
      conclusion, 24-hr sleep deprivation decreased the insulin sensitivity in healthy
      subjects without changes in cortisol levels.

PMID- 10898126
TI  - Metabolic factors that affect beta-cell function and survival.
AB  - Several data suggest that, during the natural history of Type 2 diabetes (T2DM),
      whereas the degree of insulin resistance is quite stable in a single individual,
      insulin secretion is often progressively decreasing. The decline in beta-cell
      function seems, at least in part, acquired. This review focuses on data showing
      that chronically elevated levels of glucose and fatty acids may impair beta-cell
      function and, at a later stage, also affect beta-cell survival. Results obtained
      both in vitro and in vivo demonstrate that beta-cell function is impaired after
      chronic exposure to glucose and fatty acids, with many similarities between the
      two conditions. Basal insulin release is increased as a result of an increase of
      the low-Km component of glucose phosphorylation. Glucose-induced insulin release
      is blunted, probably due to an impairment of glucose oxidation. If the metabolic
      abnormality persists in vivo or the culture is prolonged in vitro, a significant
      increase in the rate of beta-cell death was observed, eventually leading to
      severe destruction of the islet architecture. An attractive hypothesis, currently
      under investigation, is that genetic susceptibility to diabetes may confer an
      increased sensitivity to the adverse effect of high glucose and non-esterified
      fatty acid levels on beta-cell survival.

PMID- 10898127
TI  - Session on protein metabolism in the elderly. Sarcopenia of the elderly.

PMID- 10898128
TI  - Nutrition and muscle protein metabolism in the elderly.

PMID- 10898129
TI  - Exercise, ageing, and protein metabolism.

PMID- 10898130
TI  - Evaluation of insulin response in glucose tolerance test in a patient with
      Werner's syndrome: a 16-year follow-up study.
AB  - To clarify the effect of Werner's syndrome (WS) on beta-islet cell function, the
      oral glucose tolerance test (OGTT) was repeatedly performed over a period of 16
      years in one patient with WS. The data obtained on insulin secretion were
      assessed in this study. The patient was a 50-yr-old woman of consanguineous
      parentage. She presented with gray hair, cataracts, a beak-shaped nose and high
      pitched voice. She was diagnosed as WS on the basis of her characteristic
      appearance. OGTT was performed 14 times during 9 admissions to our hospital.
      After ingestion of glucose, plasma glucose (PG) levels and immuno-reactive
      insulin (IRI) at 0, 30, 60, 90, 120 and 180 min were determined. PG levels during
      OGTT gradually increased during dietary therapy and, at the age of 48, insulin
      treatment was started [PG level at 120 min during OGTT at 46 yr (before
      treatment) was 1.5 times that at 34 yr]. Insulin secretion had also gradually
      decreased during the follow-up period (sum of IRI at 34 yr during OGTT post
      treatment; 550.8 IU/ml, sum of IRI at 50 yr during OGTT post-treatment; 244.5
      IU/ml). However, the insulinogenic indices were maintained at almost the same
      level value. Our results indicate that insufficient insulin secretion, which
      could not overcome insulin resistance, might play a crucial role in the
      pathophysiology and progression of diabetes in WS along with insulin resistance
      due to a post-receptor defect.

PMID- 10898131
TI  - Ciprofloxacin 250 mg twice daily versus ofloxacin 200 mg twice daily in the
      treatment of complicated urinary tract infections in women.
AB  - In a multicenter, prospective, double-blind, double-dummy randomized study
      conducted in Israel and Germany, the efficacy and safety of ciprofloxacin 250 mg
      b.i.d. versus ofloxacin 200 mg b.i.d. was compared in the treatment of women with
      complicated lower urinary tract infection. A total of 465 women were enrolled in
      the study, 427 of whom were included in the intent-to-treat analysis. Two hundred
      fourteen received ciprofloxacin 250 mg b.i.d. and 213 received ofloxacin 200 mg
      b.i.d. Both regimens were administered for 7 days. The primary efficacy parameter
      was the microbiologic result obtained 5-9 days after cessation of therapy;
      secondary efficacy parameters were urine cultures obtained 28-42 days after the
      end of therapy and clinical outcome 5-9 days and 28-42 days post-therapy. There
      were no relevant differences in the primary efficacy parameter or in any
      secondary efficacy parameter between the average response rate of patients who
      received ciprofloxacin and that of patients who received ofloxacin: 90.1% of the
      ciprofloxacin group and 87.2% of the ofloxacin group had sterile urine 5-9 days
      after the end of therapy; 77.1% and 76.1% had sterile cultures, respectively.
      Clinical cure was achieved in 97.2% of both groups 5-9 days after cessation of
      therapy and a month later in 87.7% and 87.3%, respectively. Adverse events were
      mild and similar in both groups. In conclusion, for the primary efficacy
      parameter as well as for all secondary efficacy parameters, ciprofloxacin 250 mg
      b.i.d. is at least as effective as ofloxacin 200 mg b.i.d. in women with
      complicated lower urinary tract infection.

PMID- 10898132
TI  - Management of brain abscesses with sequential intravenous/oral antibiotic
      therapy.
AB  - Eight patients with brain abscesses who refused prolonged hospitalisation were
      treated with a short course (6-12 days) of intravenous antibiotics followed by
      prolonged treatment (15-19 weeks) with an oral antibiotic regimen consisting of
      metronidazole, ciprofloxacin and amoxicillin. All patients responded favourably
      as shown clinically and in imaging studies. No severe adverse events or sequelae
      were noted. On admission all patients had a normal or mildly impaired mental
      status, abscesses less than 3 cm in diameter and no serious predisposing factors.
      Although combined surgical/medical treatment remains the standard approach in
      management of these patients, the findings suggest that oral antibiotic therapy
      only subsequent to a short course of intravenous antibiotics may be an acceptable
      alternative in selected cases.

PMID- 10898133
TI  - Epidemiological investigation of nine respiratory pathogens in hospitalized
      children in Germany using multiplex reverse-transcriptase polymerase chain
      reaction.
AB  - The aim of this study was to generate urgently needed data on respiratory
      pathogens in German children using an economical and efficient tool.
      Nasopharyngeal aspirates of hospitalized children 0-16 years of age with an acute
      respiratory tract infection were tested by a nine-valent multiplex reverse
      transcriptase polymerase chain reaction. Of 1281 children, 449 (35%) had an acute
      respiratory tract infection caused by at least one of the organisms studied;
      there were 29 cases of dual infection. At least 34-42% of severe acute
      respiratory tract infections in children under 5 years of age were caused by
      viruses. In children over 5 years of age, this proportion was 23% (P<0.001).
      Infection during the first 2 years of life was most frequently due to respiratory
      syncytial virus (n = 162 cases). Parainfluenza virus type 3 (n = 22) and type 1
      (n = 14) were detected almost exclusively in children under 5 years of age.
      Influenza A (n = 90) and adenoviruses (n = 98) were prevalent in all age groups.
      The frequency of influenza B virus isolation (n = 17) rose significantly after
      the age of 5 years. Mycoplasma pneumoniae infection (n = 24 cases, 5.2%) was most
      frequent in 5- to 16-year-old patients. Only one case of Chlamydia pneumoniae
      infection was found. Since the distribution of pathogens within the different
      types of lower respiratory tract infections is very similar, it seems that host
      factors determine which form of lower respiratory tract infection develops in an
      individual patient. The multiplex reverse-transcriptase polymerase chain reaction
      may, in the future, become an important tool for epidemiological studies as well
      as for individual diagnosis.

PMID- 10898134
TI  - Nosocomial cluster of Candida lipolytica fungemia in pediatric patients.
AB  - Candida lipolytica has rarely been reported as a human pathogen. An apparent
      outbreak of Candida lipolytica fungemia (n = 5 cases) occurred in a pediatric
      ward over a 9-week period. The five patients infected were hospitalized in three
      adjacent rooms and cared for by the same healthcare workers. The index patient
      had central venous catheter-related fungemia, whereas the second patient, who was
      in the adjacent single room, had transient fungemia. Three additional cases of
      fungemia occurred in patients with hematological disorders who shared the same
      room; all three patients had central venous catheters and had been receiving oral
      fluconazole prophylaxis (50 mg/day for more than 3 weeks) at the time of
      infection. In vitro susceptibility testing of the strains showed that the MIC of
      fluconazole for all the isolates was 32 microg/ml. Random amplified polymorphic
      DNA analysis provided evidence of the clonal origin of the isolates, but the
      source of the outbreak was not identified. All four patients with persistent
      fungemia were successfully treated via catheter removal or empiric amphotericin B
      treatment. This outbreak shows the potential for the nosocomial epidemic
      transmission of Candida lipolytica.

PMID- 10898135
TI  - Comparison of the automated nonradiometric Bactec MGIT 960 system with Lowenstein
      Jensen, Coletsos, and Middlebrook 7H11 solid media for recovery of mycobacteria.
AB  - The aim of this study was to evaluate the sensitivity of as well as the time to
      detection of mycobacteria by three procedures: solid media with traditional
      reading, microscopy on solid media, and liquid culture using the automated
      nonradiometric Bactec MGIT 960 system. A total of 2832 respiratory specimens were
      tested, 315 of which were positive for mycobacteria. The most frequently isolated
      species was Mycobacterium tuberculosis (201 isolates). One hundred twenty
      mycobacteria other than tuberculosis were isolated, 72 of which were
      Mycobacterium xenopi strains. Sensitivity of each of the different media compared
      to all media combined for growth of Mycobacterium tuberculosis was 93%, 76.1%,
      79.6%, and 75.1% for Bactec MGIT 960, Middlebrook 7H11 plates, Lowenstein-Jensen,
      and Coletsos, respectively. Sensitivity of the Bactec MGIT 960 for detection of
      all mycobacterial isolates was 75.1%. When this automated system was supplemented
      with visual inspection, the sensitivity increased to 89.4%. The sensitivity of
      Middlebrook 7H11 plates, Lowenstein-Jensen, and Coletsos was 50.8%, 60.7%, and
      52.3%, respectively. Time to detection of Mycobacterium tuberculosis using the
      Bactec MGIT 960 system and Middlebrook 7H11 plates with microscopic reading was
      12.7 and 13 days, respectively; using the traditional Lowenstein-Jensen and
      Coletsos media, time to detection was 22.8 and 22.7 days, respectively.

PMID- 10898136
TI  - Response to replacement iron therapy in sideropenic individuals with recrudescent
      herpes labialis.
AB  - This study investigated the effects of iron replacement on the incidence of
      recurrent herpes labialis and serum ferritin levels in patients with sideropenia.
      Ten patients with diagnosed sideropenia and a history of recrudescent herpes
      labialis were prescribed ferrous sulphate for a period of 3 months. Patients were
      questioned on the number of episodes of recrudescent herpes labialis that
      developed per month before treatment and the number of episodes of recrudescent
      herpes labialis that developed per month after the commencement of replacement
      iron therapy and during the follow-up period. All blood samples were collected by
      venipuncture for assay of ferritin levels. Serum ferritin levels were
      significantly increased compared to pretreatment levels (P<0.05). The number of
      monthly episodes of recrudescent herpes labialis was reduced from 0.78 to 0.2
      episodes per month following treatment (P<0.05). The findings of this study
      suggest that iron replacement therapy should be further studied as a treatment
      option in sideropenic individuals with frequent recurrences of recrudescent
      herpes labialis.

PMID- 10898137
TI  - Differentiation of Entamoeba histolytica and Entamoeba dispar cysts using
      polymerase chain reaction on DNA isolated from faeces with spin columns.
AB  - Since Entamoeba histolytica and Entamoeba dispar were formally recognized as two
      different species at the World Health Organization (WHO)/Pan American Health
      Organization (PAHO)/United Nations Educational, Scientific and Cultural
      Organization (UNESCO) meeting in Mexico City in 1997, the specific
      differentiation of the two morphologically identical species would seem relevant
      in clinical diagnosis. Several polymerase chain reaction (PCR)-based methods have
      been described and used successfully, but methods for DNA isolation from cysts in
      stool samples are time-consuming and problematic due to inhibitory factors in
      faeces. The use of the slightly modified QIAamp tissue method (Qiagen, Germany)
      for DNA isolation was evaluated in 657 unpreserved faecal samples from cases of
      suspected Entamoeba histolytica/Entamoeba dispar infection. In only 1.7% of the
      cases was PCR hampered by inhibitors present in the faeces. The DNA isolation
      procedure was found to be rapid, simple and one that could easily be implemented
      in a routine diagnostic setting. In 98.8% of Entamoeba histolytica/Entamoeba
      dispar cyst-positive faecal samples, the true identity of the cysts could be
      determined using PCR specific for Entamoeba histolytica and Entamoeba dispar,
      respectively.

PMID- 10898138
TI  - Cutaneous aspergillosis in patients with haematological malignancies.
AB  - The aim of the present study was to evaluate skin infections caused by
      Aspergillus in patients with haematological malignancies. Fifteen cases of
      cutaneous aspergillosis are reported, 12 of which occurred among 4448 consecutive
      patients with acute leukaemia. Cutaneous involvement occurred in 4% of patients
      with documented Aspergillus infection. Primary cutaneous aspergillosis was
      diagnosed in five cases. Infection was fatal in 11 of 15 cases; the absence of
      additional sites of infection other than cutis at presentation appeared to be the
      only factor related to a favourable outcome.

PMID- 10898140
TI  - Antimicrobial resistance in European isolates of Pseudomonas aeruginosa. European
      SENTRY Participants.
AB  - Pseudomonas aeruginosa is responsible for a substantial fraction of hospital
      infections. Twenty-five European university hospitals submitted a total of 1411
      Pseudomonas aeruginosa isolates for susceptibility testing during 1997 and 1998.
      The isolates showed highest susceptibility to amikacin (87.5%), meropenem (87.3%)
      and piperacillin/tazobactam (86.8%). Susceptibility to ciprofloxacin was 73.2%.
      There was no clear geographical distribution of resistance, although isolates
      from northwestern Europe tended to be more susceptible than those from
      southeastern Europe. Isolates that were resistant to one class of antibiotics
      were also often resistant to at least one other class of antibiotics. Imipenem
      resistant isolates were generally not clonally related.

PMID- 10898139
TI  - Cost-effective algorithm for detection and identification of vancomycin-resistant
      enterococci in surveillance cultures.
AB  - A study was undertaken to develop an easy-to-use and cost-effective algorithm for
      the detection and identification of vancomycin-resistant enterococci (VRE) in
      surveillance cultures, because the incidence of VRE outbreaks in institutions
      across Canada has made continuous surveillance a necessity. Enterococcus faecium
      and Enterococcus faecalis carry transferable resistance genes and hence are a
      problem for infection control. In laboratory surveillance, however, Enterococcus
      gallinarum and Enterococcus casseliflavus, which exhibit low-level
      nontransferable resistance, are also encountered and often create confusion in
      identification. Included in this study were a total of 218 strains of enterococci
      and other streptococci isolated from surveillance cultures. Conventional methods
      were used to determine their biochemical activities, and speciation was attempted
      in 121 strains using a rapid multiplex polymerase chain reaction (PCR) method
      that utilized primers for the vanA, B, C1, C2/C3 and ddl genes. The results
      indicated that by using only a few tests (Gram stain, pyrrolidonyl arylamidase
      activity, motility, xylose and methyl-alpha-D-glucopyranoside utilization),
      Enterococcus faecium/faecalis strains could be accurately differentiated from
      Enterococcus gallinarum/casseliflavus strains. For the 121 strains on which PCR
      was performed, there was a 100% correlation with the biochemical identification,
      with the added advantage that the presence of van genes could be determined at
      the same time. The cost of identification using minimal biochemical testing and
      PCR was less than that of identification using automated systems or a battery of
      conventional biochemical methods. The algorithm presented here may be used in the
      microbiology laboratory.

PMID- 10898141
TI  - Congestive heart failure and myocarditis after seroconversion for toxoplasmosis
      in two immunocompetent patients.
AB  - Two cases of myocarditis and congestive heart failure in immunocompetent patients
      with seroconversion for toxoplasmosis are reported. Serological tests showed that
      in the first case the cardiac manifestations occurred at the time of
      seroconversion (low IgG, raised IgM and IgA), whereas in the second case they
      occurred several months after the initial infection when IgM was decreasing, IgG
      levels were very high (>1000 IU/ml) and IgG had high affinity for the antigen.
      The pathophysiological mechanisms underlying cardiac involvement in acute or
      chronic toxoplasmosis are discussed.

PMID- 10898142
TI  - Higher short-term virologic efficacy of three-class versus two-class highly
      active antiretroviral salvage therapy in HIV-infected patients.
AB  - The efficacy of two-class versus three-class antiretroviral salvage treatment was
      analyzed retrospectively in 63 HIV-infected patients in whom highly active
      antiretroviral therapy failed. Twenty-eight patients (group A) received two-class
      therapy, and 35 patients (group B) received three-class therapy. After 3 months
      of treatment, a significantly greater proportion of patients in group B (23/35,
      65.7%) than in group A (8/28, 28.5%) showed a > or = 1 log10 decrease in the
      plasma HIV RNA level (P = 0.0034). However, after 9-12 months, 12 of 23 (52.1%)
      group B responders showed viral load rebound. The results were partially
      explained by the finding that, at baseline, the great majority (21/27, 77.7%) of
      group A patients showed mutations conferring resistance to all drugs
      administered, whereas in group B patients' susceptibility to at least two drug
      classes was retained. However, after 9-12 months of therapy, most (18/20, 90%) of
      the short-term responders in group B showed emergence of additional mutations
      that hampered long-term response.

PMID- 10898143
TI  - Distribution of macrolide-resistance genes in Staphylococcus aureus blood-culture
      isolates from fifteen German university hospitals. M.A.R.S. Study Group.
      Multicentre Study on Antibiotic Resistance in Staphylococci.
AB  - The purpose of the study was to analyze the distribution of the macrolide
      resistance genes in 134 erythromycin-resistant Staphylococcus aureus blood
      culture isolates collected at 15 German university hospitals. The most prevalent
      resistance gene was ermC (68/134; 50.7%), followed by ermA (52/134; 38.8%), ereB
      (10/134; 7.5%), and mrsA/msrB (4/134; 6%). The least common genes were ermB
      (3/134; 2.2%) and ereA (1/134; 0.7%). Overall, resistance to erythromycin was
      predominantly due to the presence of two erm genes, although with different
      distributions, depending on the methicillin-resistance pattern.

PMID- 10898144
TI  - Diagnostic value of cytokine assays in cerebrospinal fluid in culture-negative,
      polymerase chain reaction-positive bacterial meningitis.
AB  - Analysis of bacterial DNA using a polymerase chain reaction performed with broad
      range eubacterial 16S rDNA primers may yield a diagnosis of bacterial meningitis
      in cases where Gram staining of cerebrospinal fluid (CFS), antigen detection
      techniques or culture fail. Since this PCR technique occasionally gives false
      positive results due to contamination of samples or laboratory reagents, a study
      was performed to establish the diagnostic value of assaying concentrations of
      tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in 90 CSF
      samples. A high correlation was found between a positive PCR result and the
      concentrations of TNF-alpha and IL-10, indicating that cytokine assays may be
      used as a confirmatory test. The findings suggested that a combination of the PCR
      technique, amplicon sequencing and assay of TNF-alpha and IL-10 concentrations in
      CSF is a reliable and cost-effective procedure for diagnosis of culture-negative
      bacterial meningitis.

PMID- 10898145
TI  - Comparative evaluation of a commercial system for identification of Candida
      lusitaniae.
AB  - The ability of the API Candida system (bioMerieux, France) to identify Candida
      lusitaniae isolates was evaluated in comparison to the Auxacolor and ID 32C
      systems using 52 clinical isolates previously identified on the basis of their
      morphology and their biochemical reactions in the Auxacolor and ID 32C systems.
      The API Candida system failed to definitively identify most of the strains tested
      within 24 h. No beta-maltosidase activity was detected in 28 strains, and
      supplementary tests were required to discriminate Candida lusitaniae, Candida
      famata and Candida guilliermondii. The API Candida system is not suitable for
      identification of Candida lusitaniae. In comparison, the Auxacolor system is easy
      to use and interpret, allowing rapid identification of this species; however, the
      ID 32C system is required for identification of atypical strains.

PMID- 10898146
TI  - Detection of Leishmania in immunocompromised patients using peripheral blood
      spots on filter paper and the polymerase chain reaction.
AB  - The aim of the present study was to investigate whether the polymerase chain
      reaction could be used to detect Leishmania infantum in peripheral blood spots of
      immunocompromised patients. Although visceral leishmaniasis in immunocompromised
      individuals is routinely diagnosed by direct microscopy or by culture of biopsy
      material, both methods have disadvantages. In order to evaluate an alternative
      method of diagnosis, blood spots were collected on filter paper from 24
      immunocompromised individuals with visceral leishmaniasis diagnosed by bone
      marrow microscopy or culture. The samples were tested using the polymerase chain
      reaction. Leishmania DNA was detected in 15 of 20 patients who had not yet begun
      treatment for Leishmania infection and in two of four patients undergoing
      treatment. Using microscopy or culture, parasites were detected in 5 of 19 and 8
      of 19 fresh blood samples, respectively. The results suggest that the polymerase
      chain reaction can be used with blood spots on filter paper as an initial
      screening method for immunocompromised patients suspected to have Leishmania
      infection.

PMID- 10898147
TI  - Splenic abscess complicating Salmonella typhi infection.

PMID- 10898148
TI  - Reduced specificity of combined IgM and IgG enzyme immunoassay testing for lyme
      borreliosis.

PMID- 10898149
TI  - New synthetic strategies for the preparation of novel chiral stationary phases
      for high-performance liquid chromatography containing natural pool selectors.
AB  - Twelve new chiral stationary phases (CSPs) for high-performance liquid
      chromatography (HPLC) were generally prepared starting from the macrocyclic
      glycopeptide antibiotic teicoplanin, according to novel and efficient 'one-pot'
      synthetic strategies. Their chiral recognition abilities were evaluated under
      polar-organic mode HPLC, towards a variety of biopharmacological interesting
      racemates, such as beta-amino acids and quaternary ammonium salts (e.g. carnitine
      and its derivatives). All materials were prepared by two different synthetic
      strategies, both leading to the formation of one or two stable ureidic functions
      on the CSP structure. The influence of the different spacers and of the silica
      matrix nature on the chiral performances was investigated. The obtained results
      suggested that the optimal synthetic strategy was that leading to the formation
      of two ureidic functions on the CSP structure, spaced-out by a six-carbon atoms
      aliphatic chain; the best chromatographic results were reached with the use of
      the spherical LiChrospher silica gel. Enantioselectivity factors (alpha)
      particularly high and short-time analyses characterised the analytical
      procedures; in addition, analytes lacking in chromophore groups were easily
      detected by evaporative light scattering (ELS) with no need of preliminary
      derivatization.

PMID- 10898150
TI  - Photostability of drugs: photodegradation of melatonin and its determination in
      commercial formulations.
AB  - The photostability of melatonin, a hormone used as supplementary drug in the
      alleviation of jet-lag and other sleep disorders, was studied. The drug
      photodegradation at different pH values was monitored by HPLC methods. The main
      photoproduct was isolated and characterised on the basis of the NMR, FTIR, and
      mass spectra. A HPLC method, in combination with a post-column on-line
      photochemical derivatisation was developed for the selective and reliable quality
      control of commercially available melatonin containing products.

PMID- 10898151
TI  - 1H-NMR and molecular modelling techniques for the investigation of the inclusion
      complex of econazole with alpha-cyclodextrin in the presence of malic acid.
AB  - Carrying on a study where the combination of alpha-cyclodextrin and malic acid
      was found to be the most effective in improving the solubility of econazole, an
      antifungal drug very poorly water soluble, in the present work 1H-NMR and nuclear
      overhauser effect (NOE) experiments and molecular modelling studies were
      performed to gain insight into the interactions in solution between such three
      components and the structure of the supposed multicomponent complex. Findings
      demonstrated that two different complexes can be simultaneously present in
      solution involving, respectively, the inclusion of econazole monochloro-phenyl
      group within the host cavity from the primary hydroxyl side of the cyclodextrin
      cavity, or that of the other phenyl group through the opposite side of the
      cavity. It was shown that also malic acid is strictly involved in the molecular
      assembly of the complex, particularly through interactions with primary hydroxyl
      groups of the cyclodextrin molecule. Molecular modelling studies allowed to
      elaborate possible geometric models of the multicomponent complex and to select
      the more energetically favourable conformations which complied better with
      experimental data. Results suggested the possible formation in solution of stable
      oligomeric aggregates constituted by the repeated concatenation of the three
      components.

PMID- 10898152
TI  - Study of beta-blockers/beta-cyclodextrins inclusion complex by NMR, DSC, X-ray
      and SEM investigation.
AB  - The formation of inclusion complexes between beta-cyclodextrin with the two beta
      blockers, atenolol and celiprolol, have been studied in the aqueous environment
      and in the solid state by nuclear magnetic resonance (NMR) spectroscopy, X-ray,
      differential scanning calorimetry (DSC) and scanning electron microscopy (SEM)
      techniques. The magnitude of the chemical shifts of the interior and exterior
      beta-cyclodextrin protons in the presence of each beta-blocker indicated that
      these are included within the beta-cyclodextrin cavity. In aqueous solution they
      form 1:1 complexes. In the solid state the formation of the beta
      cyclodextrin/atenolol (celiprolol) complexes is confirmed by X-ray, DSC and SEM,
      also employed to characterize pure substances and their physical mixtures.

PMID- 10898153
TI  - Solid-state study of polymorphic drugs: carbamazepine.
AB  - Polymorphs of a compound have solid crystalline phases with different internal
      crystal lattices; in pharmaceuticals, differences due to polymorphism and
      pseudopolymorphism can affect bioavailability and effective clinical use. The aim
      of this work was to obtain the different polymorphic modifications of the
      anticonvulsant drug, carbamazepine, and to characterise them by means of typical
      structure-sensitive analytical techniques, such as FT-IR spectroscopy, XRPD and
      DSC. Further investigations were also performed by Hot Stage FT-IR
      thermomicroscopy, which permitted the visible and spectroscopic characterisation
      of the polymorphic forms during heating. Our results confirm the existence of
      three different polymorphic forms for anhydrous carbamazepine: Form III, the
      commercial one, Form I, obtained by heating Form III and Form II, crystallised
      from ethanolic solution. Substantial differences were detected among the
      polymorphs with regard to solid-state properties. Moreover, Hot Stage FT-IR
      thermomicroscopy proved its analytical potential to characterise the drug's
      polymorphism.

PMID- 10898154
TI  - Conformational analysis of 2-hydroxy-2',5'-diazachalcones.
AB  - Spatial arrangement of 2-hydroxy-2',5'-diazachalcones was studied by means of
      infrared and NMR spectral data and molecular models calculations. The models were
      calculated in vacuum using semi-empirical AM1 method (software HyperChem 5.1).
      The initial geometries of the molecules were built by means of standard
      parameters and then optimized by Polak-Ribiere geometrical optimization. It was
      found that (E)-s-cis-conformers with synperiplanar arrangement of C-alpha and C-6
      have the lowest heats of formation (standard heat of formation).

PMID- 10898155
TI  - Electrospray characterization of selected medicinal plant extracts.
AB  - Extracts of selected medicinal plants were examined by electrospray mass
      spectrometry (ESI-MS). This technique allowed identification of the main
      components of each extract, thereby providing a typical finger-print of the
      examined plants. More specifically, anthocyanins (Vaccinium myrtillus),
      isoflavones (Glycine max, soybean), flavonol-glycosides and terpenes (Ginkgo
      biloba), triterpenes (Centella asiatica), caffeoyl-quinic acids (Cynara scolymus,
      artichoke), ginsenosides (Panax ginseng), catechins (Camellia sinensis, green
      tea) and flavones and flavanones (Propolis) were detected rapidly at levels in
      the range of 0.1-1 microg/ml, using 0.2-1 mg/ml of each medicinal plant extract.

PMID- 10898156
TI  - New biosensor for superoxide radical used to evidence molecules of biomedical and
      pharmaceutical interest having radical scavenging properties.
AB  - A superoxide dismutase biosensor was used to determine the antioxidant properties
      of scavenger molecules and the antiradical activity of healthy and diseased human
      kidney tissues; this biosensor is based on the use of the enzyme superoxide
      dismutase (SOD), which is physically entrapped in a kappa-carrageenan gel
      membrane, and of a transducer consisting of an amperometric hydrogen peroxide
      electrode. Several compounds with scavenging properties were tested, including
      some commercial drugs.

PMID- 10898157
TI  - The development of spectrophotometric and electroanalytical methods for ascorbic
      acid and acetaminophen and their applications in the analysis of effervescent
      dosage forms.
AB  - The electroanalytical study of ascorbic acid, acetaminophen and of several
      mixtures of these compounds in different ratios has been made by using a carbon
      paste electrode (CPE-graphite:solid paraffin 2:1) as working electrode and an
      Ag/AgCl reference electrode. The potential curves were recorded using different
      concentrations of ascorbic acid and acetaminophen by measuring samples between 10
      and 50 microl. The oxidation reactions were studied in a potential range from 
      0.1 to +1.3 V with different sweep rates, at different current sensitivities, in
      stationary working conditions and stirring before each replicate. The oxidation
      of ascorbic acid occurs at +0.31 +/- 0.02 V and the oxidation of acetaminophen at
      +0.60 +/- 0.05 V; meanwhile, the current has a linear variation for the following
      concentration ranges: 10(-3)-10(-2) M for the ascorbic acid and 3 x 10(-6)-7.5 x
      10(-3) M for acetaminophen (r2 = 0.999 for both ascorbic acid and acetaminophen).
      The mixtures of ascorbic acid and acetaminophen were made as follows: 1:1, 1:2,
      1:3, 2:1, and 3:1. The studies revealed the alteration of the voltammograms
      processed according to the validation methodology. The best potential variation
      range for different current sensitivities, the influence of the sweep rate, of
      the solvent volume and of the pH were studied. The mutual interferences of the
      compounds in the mixtures and the electroactive compounds in the pharmaceutical
      dosage forms, especially effervescent ones, also made the object of the research.
      The same mixtures were studied using the direct spectrophotometric method that
      revealed a lot of spectral interferences. In order to solve this problem, an
      appropriate separation or an indirect spectrophotometric method (the apparent
      content curves method) were used. The spectrophotometric and voltammetric methods
      developed were used to determine ascorbic acid and acetaminophen in different
      dosage forms (vials, tablets, suppositories and effervescent dosage forms). The
      results were compared with those obtained by other techniques.

PMID- 10898158
TI  - Flow injection analysis of cholic acids in pharmaceutical preparations using a
      polymeric membrane ISE as detector.
AB  - The results reported in this paper regard the setting up of a polymeric membrane
      ISE that is selective for cholic acids (CA) and able to work in a flow system,
      especially in flow injection analysis (FIA), based on the exchanger
      (tetrakisdecylammoniumcholate, TDACh), which has proved effective, is of very
      simple but suitable structure and is above all easy to synthesise starting from
      commercially available chemicals. A complete analytical characterisation of the
      sensor was performed working both in batch conditions and in FIA, using in the
      latter case a 'wall jet' type of flow cell. The response toward different bile
      acid sodium salts such as the CA, deoxycholic (DCA), chenodeoxycholic (CDCA),
      ursodeoxycholic (UDCA), taurocholic (TCA) sodium salts was checked. The
      application to the analysis of different commercial drugs by FIA was also
      performed to determine the UDCA or CDCA acid content of several pharmaceutical
      formulations. Lastly, a preliminary study is presented concerning the use of the
      investigated electrochemical sensor as high performance liquid chromatography
      (HPLC) detector.

PMID- 10898159
TI  - Determination of cadmium by differential pulse adsorptive stripping voltammetry.
AB  - A study of the adsorptive stripping voltammetry of cadmium on a mercury drop
      electrode is reported in which 2-mercapto-5-phenyl-amino-1,3,4-thiadiazole
      (MPATD), synthesized at home has been used as a chelating agent. The most
      suitable operating conditions and parameters such as buffer, pH, deposition
      potential, deposition time, ligand concentration, scan rate and others were
      selected and the determination of cadmium from aqueous solutions using the
      standard additions method was possible. As validation criteria, the linearity and
      range, repeatability of the signal, repeatability of the concentration and
      accuracy were investigated. A limit of detection of 4.67 x 10(-10) M and a limit
      of quantification of 1.55 x 10(-9) M were achieved. The interference of other
      metals and organic substances was studied. Concerning a possible catalytic
      effect, no one was found. The method was designed in order to determine Cd from
      biological samples.

PMID- 10898160
TI  - Simultaneous stereoselective analysis of venlafaxine and O-desmethylvenlafaxine
      enantiomers in clinical samples by capillary electrophoresis using charged
      cyclodextrins.
AB  - Capillary electrophoresis (CE) was used for the simultaneous chiral determination
      of venlafaxine (Vx), a new antidepressant drug and its main active metabolite. O
      desmethyl venlafaxine (ODV). Among the charged cyclodextrins (CD) tested,
      phosphated gamma-CD was the most appropriate. Resolution of Vx and ODV was
      obtained with 50 mM phosphate buffer (pH 2.5) containing 20 mg/ml of phosphated
      gamma-CD. After optimisation of the method (including robustness), validation was
      carried out. Vx and ODV concentrations, as well as the enantiomeric ratio, were
      investigated in clinical samples. Chiral determination of Vx and ODV was
      performed after a simple liquid-liquid extraction (LLE). In the tested
      concentration range (25-500 ng/ml), coefficients of correlation were superior to
      0.996. Within-day and between-day accuracy and precision were determined at three
      different concentrations for each enantiomer. Analyses of clinical samples (n =
      16) exhibited non-racemic ratios for Vx and ODV, which suggests a stereoselective
      metabolism in humans.

PMID- 10898161
TI  - Chiral resolution of the enantiomers of 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4
      benzothiadiazine 1,1-dioxide using high-performance liquid chromatography on
      cellulose-based chiral stationary phases.
AB  - Analytical high-performance liquid chromatography (HPLC) methods using
      derivatized cellulose chiral stationary phases (CSPs) were developed for the
      separation of the enantiomers of 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4
      benzothiadiazine 1,1-dioxide ((+/-) IDRA21). In previous studies, (+/-) IDRA21
      has been found to have an interesting inhibitory effect on the desensitization of
      alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) receptor
      and improve cognition in animals. This compound possess one chiral carbon atom,
      but very little information has been reported on the stereoselectivity of his
      activity. Therefore resolution of the enantiomers of this compound and subsequent
      identification of stereospecificity in his pharmacological actions are clearly
      matters of interest. The resolution were made under normal- and reversed-phase
      conditions using a mobile phase consisting of n-hexane:2-propanol (70/30, v/v)
      and water:acetonitrile (60/40, v/v) respectively, and a CSP of silica-based
      cellulose tris-3,5-dimethyl-phenylcarbamate (Chiralcel OD and Chiracel OD-R). The
      enantiomeric nature of eluates was confirmed by circular dichroism (CD) spectra.
      A baseline separation (R(S) > 1.5) was obtained in both cases. Furthermore the
      isolation of optical isomers of (+/-) IDRA21 was performed using a
      semipreparative column packed with the same cellulose OD CSP.

PMID- 10898162
TI  - In vitro and ex vivo anti- and prooxidant components of Cichorium intybus.
AB  - The water soluble antioxidant properties of Cichorium intybus var. Silvestre,
      whose production zone is around Chioggia, Italy, were investigated. Vegetable
      juices were obtained by centrifugation, and (1) filtration at 2 degrees C; (2)
      filtration at 25 degrees C, and stored for 3 h; (3) boiled for 30 min at 102
      degrees C, and then analysed. The antioxidant properties were evaluated in vitro
      as antioxidant activity (AA) (model system beta-carotene-linoleic acid) and ex
      vivo as protective activity (PA) against rat liver cell microsome lipid
      peroxidation measured as 2-thiobarbituric acid-reactive substances (TBA-RS)
      generated by peroxide degradation. All the vegetable juices showed high but very
      variable AA (> 83%) and PA (> 64%). After dialysis and analysis of fractions it
      was shown that the vegetable contained both biological antioxidant and prooxidant
      compounds. The prooxidants had MW < 3000, conversely the very active antioxidants
      (PA = 100%) had MW > 15,000. Electrophoretic analysis revealed that the most
      active fraction was a complex mixture of brown components at MW > 300,000.

PMID- 10898163
TI  - Capillary isotachophoretic determination of flufenamic, mefenamic, niflumic and
      tolfenamic acid in pharmaceuticals.
AB  - Anionic capillary isotachophoresis (ITP) with conductimetric detection has been
      used for determining selected non-steroid anti-inflammatory and analgesic drugs
      of the phenamate group, namely tolfenamic (I), flufenamic (II), mefenamic (III)
      and niflumic (IV) acid. Initially the pKa values (proton lost) of I-IV were
      determined as 5.11, 4.91, 5.39 and 4.31, respectively, by the UV
      spectrophotometry in aqueous 50% (w/w) methanol. The optimised ITP electrolyte
      system consisted of 10 mM HCl + 20 mM imidazole (pH 7.1) as the leading
      electrolyte and 10 mM 5,5'-diethylbarbituric acid (pH 7.5) as the terminating
      electrolyte. The driving and detection currents were 100 microA (for 450 s) and
      30 microA, respectively (a single analysis took about 20 min). Under such
      conditions the effective mobilities of I-IV varied between 23.6 and 24.6 m2 V(-1)
      s(-1) (evaluated with orotic acid as the mobility standard). The calibration
      graphs relating the ITP zone length to the concentration of the analytes were
      rectilinear (r = 0.9987-0.9999) in the range 10-100 mg l(-1) of the drug
      standard. The R.S.D.s were 0.96-1.55% (n = 6) when determining 50 mg l(-1) of the
      analytes in pure test solutions. The method has been applied to the assay of the
      phenamates in six commercial mass-produced pharmaceutical preparations (Mobilisin
      gel and ointment, Lysalgo capsules, Nifluril cream, Niflugel gel, and Clotam
      capsules). According to the validation procedure based on the standard addition
      technique the recoveries were 98.4-104.3% of the drug and the R.S.D. values were
      1.25-3.32% (n = 6).

PMID- 10898164
TI  - CZE determination of somatostatin in pharmaceutical preparations.
AB  - We propose a simple and accurate method for CE quantitative determination of
      somatostatin in pharmaceutical preparations. The method is specific for
      somatostatin as indicated by the resolution between the analyte and the analogue
      peptides which differ from somatostatin by one aminoacid. The linearity range is
      from 0.02 to 0.35 mg/ml. The recovery of the somatostatin from a pharmaceutical
      product is about 100.0%.

PMID- 10898165
TI  - Analysis and stability study of retinoids in pharmaceuticals by LC with
      fluorescence detection.
AB  - Liquid chromatographic (HPLC) methods with fluorescence detection at different
      wavelengths were developed for measurements of retinoic acids (13-cis and all
      trans) in pharmaceutical dosage forms and components of 'retinoid solution' (all
      trans retinoic acid, vitamin A palmitate and beta-carotene), a galenical of 'Di
      Bella therapy', using reversed phase columns under isocratic conditions. The
      stability of all-trans retinoic acid in cream and all-trans retinoic acid and
      vitamin A palmitate in 'retinoid solution' was investigated. Solid-phase
      extraction (SPE), using C18 sorbent was applied to the analysis of retinoic acids
      (9-cis, 13-cis and all-trans) in the 'retinoid solution' to obtain a practical
      and reliable sample clean-up. The results showed that these preparations (cream
      and solution) can be conveniently stored in the dark (t.a. or 2-8 degrees C):
      under these conditions about 86-87% of the all-trans retinoic acid initial
      concentration in both formulations and about 73-78% of vitamin A palmitate in the
      'retinoid solution' remained after 90 days, while under sunlight exposure rapid
      degradation of the drugs was observed.

PMID- 10898166
TI  - A rapid LC method for the identification and determination of CNS drugs in
      pharmaceutical formulations.
AB  - Antidepressant, neuroleptic and antiepileptic drugs were identified and
      determined in pharmaceutical formulations (tablets, capsules and oral solutions)
      by a rapid high-performance liquid chromatography method. The sample pretreatment
      consisted of a one-step extraction, filtration and dilution. The chromatographic
      conditions were: reversed-phase C8 column (150 x 4.6 mm i.d., 5 microm);
      acetonitrile-tetramethylammonium perchlorate aqueous solution (pH 2.8; 12.6 mM)
      (45:55, v/v) as the mobile phase; detection wavelength, 230 nm. Calibration
      curves were linear in the 100-1000 ng ml(-1) range for all tested drugs except
      for phenobarbital. The repeatability (or intra-day precision), expressed by the
      relative standard deviation, was better than 2.0%. The accuracy, resulting from
      recovery studies, was between 98.1 and 101.3%. The amount of drug found agreed
      with the declared content within the limits specified by United States
      Pharmacopeia and British Pharmacopeia.

PMID- 10898167
TI  - Validation of a LC method for the analysis of zafirlukast in a pharmaceutical
      formulation.
AB  - A reversed-phase high-performance liquid chromatographic (HPLC) method was
      developed and validated for estimation of zafirlukast in a pharmaceutical
      formulation. Assay samples were extracted utilizing acetonitrile. Drug and
      internal standard were chromatographed on reversed-phase C18 columns, using
      mixtures of acetonitrile/water and the eluents were monitored at different
      wavelengths. The method was validated statistically for its linearity, accuracy,
      robustness and precision. Experimental design was used during validation to
      evaluate method robustness and for the determination of intermediate precision.
      Factors examined for statistical approaches include laboratory, day, analyst,
      instrument, different percentage of organic modifier, temperature, wavelength and
      flow-rate. Due to its simplicity and accuracy, the method may be used for routine
      quality control analysis.

PMID- 10898168
TI  - A validated HPLC method for the determination of thiazinamium methylsulphate in
      pharmaceutical preparations.
AB  - The phenothiazine derivative thiazinamium methylsulphate is a drug with
      antihistaminic and anticholinergic properties, often used in some types of
      obstructive lung diseases. Because there is a lack of chromatographic data
      available for its determination, the objective of the present investigation was
      to develop a sensitive and rapid HPLC method for the quantitative estimation of
      thiazinamium methylsulphate in a pharmaceutical dosage form, applicable to
      routine analysis. The drug was chromatographed on a C18-reversed phase system
      applying a Licrocart column (LiChrospher 100 RP 18, 125 x 4 mm) with a mobile
      phase consisting of acetonitrile-water (3:7, v/v), employing as ion-pairing agent
      octanesulphonic acid sodium salt (20 mM) together with N,N-dimethyloctylamine (20
      mM), adjusted to pH 3. Detection occurred at 254 nm. Propylparaben was used as an
      internal standard. The method was applied to solutions for intramuscular
      injection containing thiazinamium methylsulphate (65 mg/2 ml). Since little
      sample preparation is required, most analyses can be carried out within 15 min.
      The optimized method was validated and provided acceptable results with respect
      to linearity (r = 0.9999), precision and accuracy in the concentration range of
      26-78 microg/ml. The proposed method is presently employed to investigate the
      stability of thiazinamium methylsulphate in solutions for intramuscular injection
      in the presence of anti-oxidizing agents.

PMID- 10898169
TI  - Simultaneous determination of losartan and hydrochlorothiazide in tablets by high
      performance liquid chromatography.
AB  - A method for the simultaneous determination of losartan potassium and
      hydrochlorothiazide in tablets is described. The procedure, based on the use of
      reversed-phase high-performance liquid chromatography, is linear in the
      concentration range 3.0-7.0 microg ml(-1) for losartan and 0.5-2.0 microg ml(-1)
      for hydrochlorothiazide, is simple and rapid and allows accurate and precise
      results. The limit of detection was 0.08 microg ml(-1) for losartan and 0.05
      microg ml(-1) for hydrochlorothiazide.

PMID- 10898170
TI  - Determination of anthocyanins in blood orange juices by HPLC analysis.
AB  - Determination of anthocyanins in fresh and concentrated juices can be a parameter
      for the assessment of authenticity and quality of blood orange juices. This work
      reports an HPLC/UV-Vis method developed for quantitative determination of
      anthocyanins in blood orange juices, by using a calibration curve obtained for
      standard cyanidin-3-glucoside. Samples analysed have been obtained from fruits of
      different trees (one for each of the varieties: 'Moro', 'Tarocco', 'Sanguinello'
      and 'Sanguinello nocellare') harvested about every 15 days during the 1998
      productive season. Seasonal variation has been also evaluated. HPLC results were
      compared with spectrophotometric measurements, using a calibration curve obtained
      for cyanidin-3-glucoside solutions. The two methods showed good agreement, but
      the results obtained greatly differed with the data reported in the literature.

PMID- 10898171
TI  - Headspace SPME method development for the analysis of volatile polar residual
      solvents by GC-MS.
AB  - A solid-phase microextraction (SPME) method has been developed and optimized for
      the polar residual solvent determination in pharmaceutical products. Five
      different polymer-coated fibers were investigated and the
      Carboxen/polydimethylsiloxane was found to be the most sensitive for all
      components. Two Headspace SPME methods were developed and optimized: one for the
      extraction from aqueous solutions, and the other for the extraction from organic
      solutions (N,N-dimethyl formamide (DMF) and dimethyl sulfoxide (DMSO). The
      optimum equilibration time for all components and all systems was 30 min. It was
      found that the sample headspace volume has an important effect on method
      sensitivity and precision. At low headspace volumes (less than one-third of the
      vial volume), sensitivity improves but at the same time, precision worsens. For
      10 ml headspace vials, the optimum headspace volume was found to be 3 ml. The
      total volatile organic content in the sample also has an important effect on
      method sensitivity and precision. At low organic content, sensitivity increases
      but precision drops significantly. Over 0.5% volatile organic content in the
      sample, the system becomes unstable due to stationary phase swelling by the
      organic components, and also the sensitivity of the method is drastically
      reduced. The optimum range for total volatile organic content was found to be
      between 0.01 and 0.1%. The added Na2SO4 quantity increases the extraction yield.
      It was found that slightly pressurizing the headspace vial improves the
      sensitivity of the method by a factor of 2. For the organic system, it was found
      that the addition of 100 microl DMSO or DMF to 50 mg drug substance and slightly
      pressurizing the headspace vial gives good results in terms of sensitivity and
      reproducibility. The measured detection limits were between 0.4 and 200 ng/ml,
      and the relative standard deviation data were between 2 and 9%. The Headspace
      SPME from aqueous solutions was found to be ten times more sensitive than
      Immersion SPME and Headspace SPME from organic solutions.

PMID- 10898172
TI  - Detection of beta-blockers in human urine by GC-MS-MS-EI: perspectives for the
      antidoping control.
AB  - We have developed a general method for the detection of beta-blockers and/or of
      their metabolites in human urine. The method comprises a pretreatment procedure
      (enzymatic hydrolysis, liquid/liquid extraction and derivatization by
      pentafluoropropionic anhydride, PFPA), carried out on an initial aliquot of 2.5
      5.0 ml of urine, and the instrumental analysis of the derivatives, performed by
      GC-MS-MS (ion trap) with electronic impact ionization (EI). The GC-MS-MS analysis
      allows to isolate and to characterize specific fragments of the original
      molecular structure, and particularly the fragments originating from parent ion
      clusters specific for all beta blocking drugs, giving rise to m/z = 366 and 202
      ions respectively. MS-MS analysis of the parent ion allows checking for the
      presence of the above-mentioned peaks in the GC-MS chromatogram. The proposed
      method is capable of detecting a great variety of known (and possibly also of
      newly synthesized) beta-blockers, with an average sensitivity limit of 20 ng/ml
      of drug/metabolite in urine. The method is presently being evaluated as a general
      screening protocol to be followed by an antidoping laboratory to detect illicit
      beta-blockers administration to the athletes.

PMID- 10898174
TI  - Diffusion coefficient (or concentration) determination of ascorbic acid using
      carbon paste electrodes in Fredholm alternative.

PMID- 10898173
TI  - Trolox equivalent antioxidant capacity (TEAC) of Ginkgo biloba flavonol and
      Camellia sinensis catechin metabolites.

PMID- 10898175
TI  - Study of the inclusion complex of atenolol with beta-cyclodextrins.

PMID- 10898176
TI  - Optimization of HPLC analysis for the determination of propylthiouracil levels in
      plasma and serum.

PMID- 10898177
TI  - Predictive factors associated with axillary lymph node metastases in T1a and T1b
      breast carcinomas: analysis in more than 900 patients.
AB  - BACKGROUND: Axillary lymph node metastasis (ALNM) represents the single most
      important prognostic indicator in patients diagnosed with breast cancer. The
      proportion of < or = 1-cm (T1a, T1b) invasive breast carcinomas is increasing.
      The incidence and predictive factors associated with ALNM in patients with < or =
      1-cm tumors remains unclear and the role of axillary lymph node dissection in
      these patients has been questioned. The purpose of this study was to determine
      clinical and pathologic factors predictive of ALNM in patients with < or = 1-cm
      invasive breast carcinomas by univariate and multivariate analyses. STUDY DESIGN:
      Review analysis from a prospective database identified patients with < or = 1-cm
      invasive breast cancers treated at our institution between 1990 and 1996. All
      patients underwent a resection of the primary tumor and axillary lymph node
      dissections. Routine patient and tumor characteristics evaluated included: age,
      race, tumor size, histologic grade, estrogen and progesterone receptor status,
      and lymphatic and vascular invasion. Univariate and multivariate analyses were
      performed. Adjusted odds ratios (OR) and 95% confidence intervals (CI) are
      presented. RESULTS: A total of 919 patients were identified in this study with
      tumors < or = 1 cm. These included 199 patients (21.7%) with T1a tumors and 720
      patients (78.3%) with T1b tumors. ALNM was detected in 165 patients with an
      overall incidence of 18.0%. Of the ALNM group, 32 patients (19.4%) had T1a tumors
      and 133 patients (80.6%) had T1b tumors. Four variables were found to be
      significant in univariate analysis. These included: increasing tumor size, poor
      histologic grade, presence of lymphatic or vascular invasion, and younger age of
      the patient. An increase in tumor size was associated with a significant risk of
      ALNM (OR = 2.66, 95% CI = 1.28 to 5.75; p = 0.01). Poor tumor grade and the
      presence of lymphatic or vascular invasion were also associated with an increased
      risk of ALNM (OR = 2.69, p = 0.003 and OR = 5.52, p = 0.0001, respectively).
      Patients with ALNM were more likely to have a tumor grade of 3 (25.0% ALNM versus
      12.5% node-negative, p = 0.004) and lymphatic or vascular invasion (16.9% ALNM
      versus 3.5% node-negative, p < 0.0001). In multivariate analysis, an increased
      risk of ALNM was demonstrated with increasing tumor size (0.1-cm increments),
      poor histologic grade, and younger age. CONCLUSIONS: This study investigated
      clinical and pathologic factors influencing ALNM in patients with T1a and T1b
      breast carcinomas. We have identified three factors by multivariate analysis as
      significant independent predictors of ALNM in this group of patients. These
      include increasing tumor size, poor histologic grade, and younger age. Given the
      significant amount of ALNM demonstrated in this study (overall 18%) and the
      inability to identify a subgroup of patients that had an acceptable low risk of
      ALNM, the complete omission of assessing the axilla for metastatic disease in
      patients with small breast cancers cannot be advocated. Our recommendation for
      patients diagnosed with T1a and T1b tumors is to have their axilla investigated
      for metastatic disease either by traditional axillary lymph node dissections or
      by intraoperative lymphatic mapping and sentinel lymph node biopsy techniques.

PMID- 10898178
TI  - Use of advanced breast biopsy instrumentation while performing stereotactic
      breast biopsies: review of 150 consecutive biopsies.
AB  - BACKGROUND: Stereotactic breast biopsies are being performed in the United States
      with increasing frequency. Advanced breast biopsy instrumentation (ABBI) is a
      recent addition to the list of available stereotactic breast biopsy devices (eg,
      fine-needle aspiration, automated needle cores, and vacuum-assisted devices).
      Indications for the ABBI procedure in the management of patients with nonpalpable
      mammographic lesions have not been established. STUDY DESIGN: Prospectively
      collected data on 150 patients biopsied with the ABBI procedure were reviewed.
      RESULTS: From April 1996 to May 1997, 150 patients with indeterminate or
      suspicious nonpalpable mammographic lesions were biopsied using the ABBI
      technique. Complications were minor. One patient (0.6%) required a repeat biopsy
      because of insufficient tissue and one patient had repeat excision to confirm the
      diagnosis of atypical ductal hyperplasia. Cancer was diagnosed in 26%. Followup
      mammograms were obtained in 94% of the patients. Lesions were missed in three
      patients (2%), none of whom were later found to have cancer. One patient (0.6%)
      required a repeat ABBI biopsy for postbiopsy architectural distortion.
      Postprocedure mammographic scarring was otherwise minimal and was noted in only
      16% of the patients. Of the 111 patients with benign diagnoses, 67 were seen for
      clinical followup; 98% had good cosmetic outcomes and were satisfied with the
      ABBI technique. CONCLUSIONS: The ABBI technique is a safe, reliable stereotactic
      breast biopsy technique that is well accepted by patients. The sensitivity and
      specificity of ABBI biopsy for the diagnosis of carcinoma in this series were
      each 100% for the 142 patients returning for followup. Indications for the
      technique are similar to those for traditional needle localization excisional
      breast biopsies.

PMID- 10898179
TI  - Judging the therapeutic value of lymph node dissections for melanoma.
AB  - BACKGROUND: The management of the regional lymph nodes remains controversial for
      early-stage melanoma and for those patients with lymph node metastases; American
      Joint Committee on Cancer stage III. This study examines the importance of
      quality of the surgical resection measured by the extent of lymph node dissection
      (quartile of the total number of lymph nodes removed) to determine if this factor
      is an important prognostic factor for survival. STUDY DESIGN: We reviewed our
      computer-assisted database of more than 8,700 melanoma patients prospectively
      collected from 1971 through the present to identify patients who underwent lymph
      node dissection for stage III melanoma. We included only patients who had their
      nodal dissections performed at our institute. Patients who underwent sentinel
      lymph node dissection were excluded. These patients were then analyzed as a group
      and by individual lymphatic basins: cervical, axillary, and inguinal basins.
      Univariate and multivariate analyses were used to examine the model that included
      tumor burden, thickness of the primary melanoma, gender, age, clinical status of
      the lymph nodes (palpable versus not palpable), and the primary site. The
      survival and recurrence rates were analyzed using the Cox proportional hazards
      model. RESULTS: Five hundred forty-eight patients underwent regional lymph node
      dissections. Of these patients, 214 underwent axillary dissections, 181 inguinal
      dissections, and 153 cervical dissections. The extent of the nodal dissections
      was based on the quartile of nodes excised, ranging from 1 to 98 (mean +/- SD =
      25.8 +/- 15.8). Patients were stratified by tumor burden and quartile of number
      of lymph nodes removed. The overall 5-year survival of patients with four or more
      lymph nodes having tumor and the highest quartile of lymph nodes removed was 44%
      and was 23% for the lowest quartile of total lymph nodes excised (p = 0.05). By
      univariate analysis, tumor burden (p = 0.0001), quartile of total lymph nodes
      removed (p = 0.043), and primary site (p = 0.047) were statistically significant
      for predicting overall survival. Gender, clinical status of the nodes, primary
      tumor thickness, age, and dissected basin were not significant (p > 0.05). By
      multivariate analysis only the tumor burden (p = 0.0001) and quartile of lymph
      nodes resected (p = 0.044) were statistically significant. CONCLUSIONS: The
      extent of lymph node dissection for melanoma when analyzed by quartiles is an
      independent factor in overall survival. This factor appears to be more important
      with increasing tumor burden in the lymphatic basin. The extent of lymph node
      dissection should be considered as a prognostic factor in the design of clinical
      trials that involve stage III melanoma.

PMID- 10898180
TI  - Minimally invasive radioguided parathyroidectomy.
AB  - BACKGROUND: Minimally invasive radioguided parathyroidectomy (MIRP) combines
      technetium sestamibi scan, intraoperative gamma probe, methylene blue dye, and
      measurement of circulating parathyroid hormone (PTH) levels. STUDY DESIGN: All
      patients presented with biochemically proved primary hyperparathyroidism. A
      technetium sestamibi scan was performed preoperatively. Technetium sestamibi and
      methylene blue dye (7.5 mg/kg) were administered IV on the day of operation.
      Operative dissection was directed by the gamma probe. Blood samples for PTH assay
      were obtained before and after excision of an abnormal gland. When an appropriate
      decrease in the PTH assay was obtained, the exploration was concluded. Persistent
      PTH elevation instigated further neck exploration. RESULTS: Thirty-six
      consecutive patients were explored for untreated primary hyperparathyroidism and
      three for recurrent hyperparathyroidism. Hypercalcemia was corrected in all 39
      patients. A single adenoma was found in 32 of 36 patients with untreated primary
      hyperparathyroidism, and a single abnormal gland was identified in all of those
      with recurrent hyperparathyroidism. Persistently elevated PTH prompted further
      exploration in two patients, identifying a second abnormal gland in one and
      hyperplasia in the other. Minor local complications occurred in 8% (3 of 39) of
      the patients. Forty-four percent (16 of 36) of the patients were discharged on
      the day of operation and 83% (30 of 36) within 23 hours after the initial neck
      exploration for primary hyperparathyroidism. Comparison of charges for MIRP with
      charges for "standard" neck exploration revealed lower costs with MIRP because of
      decreased duration of the operation, anesthesia, and hospital stay, and
      elimination of intraoperative histologic analysis. CONCLUSIONS: MIRP is a safe
      and effective procedure, resulting in the correction of hypercalcemia in all
      patients. The combination of intraoperative gamma probe and methylene blue dye
      allows rapid identification of the abnormal gland with minimal dissection through
      a small incision. PTH assay after excision provides biochemical confirmation that
      the abnormal gland has been removed. Most patients undergoing MIRP can be treated
      on an outpatient basis. Low postoperative complications, a small incision, and
      rapid return to normal activities resulted in very high patient acceptance of the
      procedure.

PMID- 10898181
TI  - Gastric outlet obstruction resulting from peptic ulcer disease requiring surgical
      intervention is infrequently associated with Helicobacter pylori infection.
AB  - BACKGROUND: Gastric outlet obstruction (GOO) secondary to peptic ulcer disease
      requiring therapeutic intervention remains a common problem. The incidence of
      Helicobacter pylori infection in this cohort has not been well defined. Pneumatic
      dilatation (PD) has been proposed as first-line therapy before surgical
      intervention. If H pylori infection in patients with GOO is infrequent, PD may
      not offer permanent control without the need for longterm antacid therapy. STUDY
      DESIGN: The purpose of this study was to examine the incidence of H pylori
      infection and surgical outcomes in patients undergoing resection for GOO. The
      records of all patients having resection (vagotomy and antrectomy) for benign
      disease from 1993 to 1998 for GOO at the University of Tennessee affiliated
      hospitals were reviewed retrospectively. Smoking history, NSAID use, weight loss,
      previous ulcer treatment, previous treatment for H pylori, and previous attempts
      at PD were among the factors examined. H pylori infection was documented by
      Steiner stain from either preoperative biopsy or, in most patients, final
      surgical specimens. Surgical complications and patient satisfaction were
      ascertained from inpatient records, postoperative clinical notes, and, where
      possible, followup telephone surveys. RESULTS: Twenty-four patients underwent
      surgical resection during the study period. There were 16 men and 8 women, with a
      mean age of 61 years (range 40 to 87 years). Weight loss was documented in 58%
      and averaged 27 lb. Five of 24 patients had previous attempts at PD, 3 of whom
      were H pylori negative. All five had further weight loss after these failed
      attempts. Of the 24 patients reviewed, only 8 (33%) were H pylori positive. There
      were no procedure-related deaths. Longterm clinical followup was possible in 16
      of 24 patients, and all but one demonstrated dramatic clinical improvement by
      Visick score. CONCLUSIONS: We conclude the following: 1) In this cohort, H pylori
      infection was present in a minority; 2) previous attempts at PD were
      unsuccessful, which may be related to the H pylori-negative status of the
      patients; 3) mortality related to the operation was zero; and 4) patient
      satisfaction was positive by the Visick scale. Patients with H pylori-negative
      GOO resulting from peptic ulcer disease should be strongly considered for an
      early, definitive, acid-reducing surgical procedure.

PMID- 10898182
TI  - Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the
      actual risk of liver resection.
AB  - BACKGROUND: Recent reports highlighting reduced mortality rates to less than 1%
      after hepatic resections have evaluated the management of selected patients. The
      current risk of liver resection in unselected patients needs to be more clearly
      defined to appreciate the actual risk of new indications. STUDY DESIGN: From 1990
      to 1997, 747 consecutive patients, including 16 operated in emergency, underwent
      hepatic resection. Resection was indicated for malignancy in 473 patients (63%).
      Major resections were performed in 333 patients (45%). An underlying liver
      disease, including cirrhosis (n = 239) and obstructive jaundice (n = 4), was
      present in 253 patients (35%). Multivariate analysis of the risk factors for
      postoperative mortality, morbidity, and transfusion after stratifying patients
      for the circumstance of the operation and the pathological changes of the remnant
      liver was performed. RESULTS: There was no intraoperative death and the overall
      mortality rate was 4.4%. This rate was 25% after emergency liver resection and
      3.9% after elective liver resection (p < 0.001). After elective resection,
      mortality was significantly higher in patients with cirrhosis (8.7%) or
      obstructive jaundice (21%) than in patients with a normal liver (1%; p < 0.001).
      Analysis of this subgroup of 478 patients with normal liver showed that the
      mortality rate was 0% in 220 patients operated for a benign disease and in 263
      patients who underwent minor resections. All five deaths occurred in patients
      with a malignancy and resulted from extrahepatic complications. In patients with
      a malignancy, the only independent predictor of death was an associated
      extrahepatic procedure. The incidence of postoperative complications was 22% and
      was influenced by the American Society of Anaesthesiology (ASA) score, extent of
      resection, presence of a steatosis, and an associated extrahepatic procedure. The
      incidence of major complications was 8% and of reoperation 3%. Perioperative
      blood transfusion was required in 112 of 478 (23%) and was not associated with
      increased mortality. CONCLUSIONS: The 1% basic risk of elective liver resection
      on normal liver suggests that indications of resection for malignancy could be
      extended, unless an associated extrahepatic procedure is needed. Because of this
      low basic risk, future studies evaluating resection on normal liver should not
      consider in-hospital mortality as the only end point.

PMID- 10898183
TI  - Objective evaluation of liver consistency to estimate hepatic fibrosis and
      functional reserve for hepatectomy.
AB  - BACKGROUND: The empiric evaluation of liver consistency is currently used to plan
      the surgical strategy. The aim of this study was to verify the feasibility of the
      objective measurement of liver consistency and to check its correlation with
      liver fibrosis and liver functional reserve. STUDY DESIGN: Fifty-two consecutive
      patients who underwent hepatic resections in our department were enrolled. The
      indications for liver resection were hepatocellular carcinoma in 36 patients,
      metastatic liver tumors in 12 patients, and other conditions in 4 patients. Liver
      consistency was measured with a new tactile sensor. A fibrosis index was
      calculated as an expression of the percentage of fibrotic tissue. Liver
      consistency was compared with the degree of liver fibrosis observed in histologic
      specimens (fibrosis index) and with liver function parameters. RESULTS: Liver
      stiffness showed a significant positive correlation with fibrosis index (r =
      0.887, p < 0.0001). Liver stiffness also showed significant positive correlation
      with the indocyanine green test (r = 0.631, p < 0.0001) by a univariate analysis.
      The indocyanine green test and platelet count were independently and
      significantly associated with liver stiffness by a multiple regression analysis.
      In five patients, the liver stiffness values measured intraoperatively differed
      markedly from those expected from the indocyanine green test values. In these
      patients, the operative procedures were finally selected based on the liver
      stiffness measured with the tactile sensor and good clinical outcomes were
      obtained. CONCLUSIONS: These results show for the first time that liver stiffness
      can be clinically assessed quantitatively by means of the tactile sensor. The
      tactile sensor adequately estimates liver stiffness and this estimation is well
      correlated with liver fibrosis and functional reserve. Liver consistency
      determined objectively in this manner may be useful for optimizing surgical
      decision making.

PMID- 10898184
TI  - Experimental discordant hepatic xenotransplantation in the recipient with liver
      failure: implications for clinical bridging trials.
AB  - BACKGROUND: Clinical xenotransplantation might start with bridge-to-bridge
      trials. Situations where hyperacute rejection is avoided would provide
      opportunities for the initiation of bridging trials. Patients with liver failure
      have a diminished capacity to initiate antibody and complement-induced injury of
      xenogeneic endothelium. Hyperacute rejection of a liver xenograft manifests as a
      coagulopathy. We examined the ability of a recipient with liver failure to
      hyperacutely reject a liver xenograft in the dog-to-pig model in the immediate
      postoperative period. STUDY DESIGN: Liver failure in pigs was induced with
      galactosamine. Canine livers were transplanted into pigs with liver failure and
      into healthy pigs. The postoperative course was monitored for 1 hour for
      histologic changes in the xenograft, changes in platelet counts, and whole blood
      clotting with Sonoclot analysis. In vitro assays with pig serum and canine
      hepatic sinusoidal endothelial cells were used to assess the effect of liver
      failure on serum cytotoxicity and xenoreactive antibody levels. RESULTS: All
      untreated pig recipients of liver xenografts died from a coagulopathy. Recipients
      with liver failure manifested no signs of coagulopathy, and had minimal change in
      platelet counts or Sonoclot (Sienco Inc., Morrison, CO) tracings. Liver xenograft
      biopsies from recipients with liver failure showed no evidence of the tissue
      injury that characterized the biopsies of control recipients. Serum from pigs was
      less cytotoxic to the canine hepatic sinusoidal endothelium after induction of
      liver failure. The xenoreactive antibody levels and repertoire were similar in
      the pig serum before and after liver failure was induced. CH50 (total complement)
      levels were diminished in pigs after the induction of liver failure. CONCLUSIONS:
      Liver xenotransplantation used in bridging trials in recipients with liver
      failure might not face the barrier of hyperacute rejection.

PMID- 10898185
TI  - Chemically assisted dissection of tissues: an interesting support in abdominal
      myomectomy.
AB  - BACKGROUND: The aim of this study was to verify the efficacy of sodium-2
      mercaptoethanesulfonate (mesna) in the chemical separation of tissues in
      abdominal myomectomies when used with the traditional mechanical separation
      techniques. STUDY DESIGN: In a prospective, randomized study, 58 women underwent
      abdominal myomectomy. In 29 of these, we used mesna for highlighting and
      separating tissues, and in the other 29 we used saline solution for the same
      purposes. The variables evaluated included the number of myomas removed, the
      volume of the biggest myoma, and the total volume of the myomas removed in every
      intervention. We also recorded operating time, the length of hospital stay, the
      degree of procedure difficulty, perioperative blood loss, operative
      complications, and cost. RESULTS: The operation was significantly shorter in the
      mesna group (p < 0.05) even though the volume and the number of myomas were
      larger. The degree of difficulty evaluated by the surgeon at the end of every
      operation was not significantly different in the two groups. The reduction in
      hemoglobin 24 hours after operation was significantly less in the patients
      treated with mesna (p = 0.006), but this difference was probably altered by the
      increase in hematocrit levels. CONCLUSIONS: Because of its ability as a chemical
      dissector, mesna may be a useful aid in this type of benign gynecologic
      operation. Larger studies to confirm this are needed.

PMID- 10898186
TI  - Sir James Paget (1814-1889): a great academic Victorian.

PMID- 10898187
TI  - Vascular drugs in the new millennium.

PMID- 10898188
TI  - Antisense oligonucleotides: an evolving technology for the modulation of gene
      expression in human disease.

PMID- 10898189
TI  - Images for surgeons. Congenital bronchoesophageal fistula in an adult.

PMID- 10898190
TI  - Images for surgeons. Parastomal squamous cell carcinoma in an ileostomy 44 years
      after proctocolectomy.

PMID- 10898191
TI  - Laparoscopic biopsy of abdominal retroperitoneal lymphadenopathy for the
      diagnosis of lymphoma.

PMID- 10898192
TI  - Completely laparoscopic proximal gastrectomy with jejunal interposition and
      lymphadenectomy.

PMID- 10898193
TI  - Striving for statistical significance: how important is it?

PMID- 10898194
TI  - Clinical failure after posterior wall acetabular fractures: the influence of
      initial fracture patterns.
AB  - OBJECTIVE: To determine radiographic and clinical features that predict rapid
      failure after open reduction and internal fixation of posterior wall acetabular
      fractures. DESIGN: Retrospective radiographic review and patient follow-up study.
      SETTING: University hospital. PATIENTS: Forty-two patients with posterior wall
      acetabular fractures. INTERVENTION: Open reduction and internal fixation. MAIN
      OUTCOME MEASURES: Radiographs, Merle D'Aubigne scores, Musculoskeletal Functional
      Assessment. RESULTS: Eleven patients had complete loss of joint space by one year
      postinjury; eight of these individuals required reconstructive surgery. These
      patients more commonly had fractures with comminution of three fragments or more
      (p = 0.001) or fracture into the subchondral arc at the level of the acetabular
      roof (p = 0.045). CONCLUSION: Poor outcomes after open reduction and internal
      fixation are associated with certain types of posterior wall fracture patterns.

PMID- 10898195
TI  - Pelvic fractures in pregnant multiple trauma patients.
AB  - OBJECTIVE: To study the outcome of pelvic fractures and fetuses in pregnant
      patients involved in blunt multiple trauma. DESIGN: Retrospective follow-up
      study. SETTING: Level I trauma center. PATIENTS: Pregnant multiple trauma
      patients with pelvic fractures between 1974 and 1998. INTERVENTIONS: Conservative
      and operative treatment of pelvic fractures adapted to the clinical status of the
      mother. MAIN OUTCOME MEASURES: Clinical, functional, and social outcomes were
      evaluated. RESULTS: Out of 4,196 patients with blunt multiple trauma treated
      between 1974 and June 1998, seven demonstrated the combination of blunt multiple
      trauma, pregnancy, and pelvic fractures. These patients had a mean Injury
      Severity Score of 29.9 points. Five mothers and three fetuses survived their
      injuries. All dead fetuses died on the scene. One surviving fetus was found to
      have hydrocephalus unrelated to the injury; the remaining fetuses had an
      uneventful delivery and were healthy. In two of the three patients whose fetuses
      survived, the treatment of the pelvic fracture was modified for the sake of fetal
      well-being. In all of these patients, acceptable outcome was achieved.
      CONCLUSION: Modification of the treatment of the pelvic fracture in pregnant
      women with multiple trauma may be necessary to minimize the risk of fetal injury.
      In our experience with these rare cases, this modified treatment did not severely
      alter the clinical outcome of the mother's pelvic fracture.

PMID- 10898196
TI  - Electromyography monitoring for percutaneous placement of iliosacral screws.
AB  - OBJECTIVE: To report our experience with the use of continuous electromyography
      (EMG) for placement of iliosacral screws. DATA SOURCES: Concurrently acquired
      data as well as patient charts, intraoperative EMG records, x-rays, and pelvic
      computed tomography (CT) scans. DESIGN: The monitored group of twenty-nine
      patients was studied prospectively. The control group consisted of twenty-two
      patients studied retrospectively. SETTING: Level One trauma center. METHODS:
      Continuous electromyograms were recorded for twenty-nine patients and compared
      with those from a group of twenty-two antecedent patients who were not monitored.
      The primary parameter of interest of this study was the presence or absence of
      neurologic change after iliosacral screw placement. This information was obtained
      prospectively in the study group and by retrospective review in the historical
      control. RESULTS: Four patients in the control group had postoperative and/or
      sensory motor changes prompting a postoperative CT scan; in each of these
      patients, a misdirected screw was identified and subsequently removed in a second
      procedure. There were no neurologic changes subsequent to placement in the twenty
      nine patients who were monitored (7.5 percent versus 0 percent; p = 0.029,
      Fisher's exact test). All monitored patients had postoperative CT scans and
      showed the screw in a safe position with no significant violations of the S1
      tunnel. CONCLUSION: Continuous EMG monitoring during iliosacral screw placement
      may be a useful neuroprotective tool.

PMID- 10898197
TI  - Intraneural sciatic nerve pressures relative to the position of the hip and knee:
      a human cadaveric study.
AB  - OBJECTIVES: To determine the effects of ipsilateral hip and knee position on
      intraneural sciatic nerve pressures. DESIGN: Intraneural sciatic nerve pressures
      measured in intact, fresh cadaveric specimens relative to ipsilateral hip and
      knee positions. LOCATION: Medical school anatomy laboratory. SUBJECTS: Randomly
      acquired adult cadavers. INTERVENTION: Pressure transducer placed within the
      sciatic nerve distal to the femoral attachment of the gluteus maximus.
      Intraneural pressures measured with the hip placed in 0, 45, and 90 degrees of
      flexion while the knee was positioned in 90, 45, and 0 degrees of flexion. MAIN
      OUTCOME MEASUREMENTS: Tissue fluid pressures within the sciatic nerve relative to
      the position of the ipsilateral hip and knee. Tissue fluid pressure within the
      sciatic nerve exceeded previously defined critical thresholds for alteration of
      neural microcirculation and function. Although increased intraneural pressures
      were realized as the hip was positioned in greater flexion and the knee was
      extended, clinically relevant pressures were realized only when the hip was
      flexed to 90 degrees and the knee was fully extended. Pressures with the limbs in
      these positions were fifty-five millimeters of mercury (range 38 to 74
      millimeters of mercury). RESULTS: With the hip held flexed to 90 degrees,
      statistically significantly increased intraneural pressures were measured as the
      knee was extended from 90 to 45 degrees of flexion (p = 0.048) and again from 45
      to 0 degrees of flexion (p < or = 0.01). With the knee positioned in 45 degrees
      of flexion, statistically significantly increased intraneural pressures were
      measured as the hip was flexed from 45 to 90 degrees (p < or = 0.0062). When the
      knee was held fully extended, statistically significantly increased intraneural
      pressures were measured as the hip was flexed from 0 to 45 degrees of flexion (p
      = 0.0006) and again when the hip was brought from 45 to 90 degrees of flexion (p
      < or = 0.01). CONCLUSIONS: Intraneural sciatic nerve pressures are influenced by
      the position of the ipsilateral hip and knee. The magnitude of the pressure
      elevation appears to be related to the excursion of the nerve as the linear
      distance between the greater sciatic notch and the distal aspect of the leg
      increases. Intraneural tissue fluid pressures measured within a localized section
      of the sciatic nerve appeared to exceed published critical thresholds for
      alterations of blood flow and neural function only when the hip was flexed to 90
      degrees and the knee was fully extended.

PMID- 10898198
TI  - Superior gluteal artery in the extended iliofemoral approach.
AB  - OBJECTIVE: To determine the incidence of superior gluteal artery injury following
      fracture of the acetabulum and to determine whether the combination of a superior
      gluteal artery injury and the use of an extended iliofemoral approach to the
      acetabulum creates abductor muscle necrosis. DESIGN: Prospective protocol,
      consecutive cases. SETTING: A consecutive series from the referral practice of
      the senior author plus seven cases from the practices of two other authors.
      PATIENTS: Two hundred twenty-seven patients with fractures of the acetabulum were
      treated operatively between November 1992 and January 1995. Forty-one were
      treated with the use of the extended iliofemoral approach. Preoperative
      angiograms were not performed for any of the patients. All fractures involved the
      posterior column, and all but two fractures had displacement of the greater
      sciatic notch. The average displacement of the notch was 2.5 centimeters (range 6
      to 60 millimeters). INTERVENTION: All patients were treated with open reduction
      and internal fixation via the extended iliofemoral approach. Intraoperative
      Doppler examination of the superior gluteal artery was performed before and after
      reduction and fixation of the posterior column. MAIN OUTCOME MEASURE: Wound
      complications, abductor manual muscle testing, hip range of motion. RESULTS:
      Pulsatile flow was confirmed in forty of forty-one patients. All patients were
      followed for a minimum of six months with an average follow-up of 1.4 years. At
      most recent follow-up, no patients had evidence of complete loss of abductor
      function. Sixty-three percent of patients had achieved Grade 4 of 5 motor
      strength, and 25 percent of them had achieved normal motor strength. CONCLUSIONS:
      No instances of superior gluteal artery laceration and only one instance of
      superior gluteal artery thrombosis were encountered in these forty-one patients
      despite significant fracture displacement involving the sciatic notch. The
      incidence of superior gluteal artery injury was significantly less than would be
      expected from previous studies. Massive abductor necrosis resulting from superior
      gluteal artery injury combined with an extended approach has been described
      primarily in animal and cadaver studies. Although arteriograms are useful in the
      control of hemodynamic instability, we cannot support the recommendation of
      preoperative angiographic study of all patients undergoing acetabular fracture
      surgery via an extended approach. In one case, an extended iliofemoral approach
      was tolerated in a patient with absent superior gluteal artery flow.

PMID- 10898199
TI  - Safe placement of S1 and S2 iliosacral screws: the "vestibule" concept.
AB  - OBJECTIVES: To determine the optimal starting points for placement of S1 and S2
      iliosacral screws as well as the pertinent anatomy surrounding the S1 and S2
      vertebral bodies. DESIGN: Normal subject study evaluating helical CT scans of
      thirty normal posterior pelvic rings. SETTING: Methodist Hospital, Indianapolis,
      Indiana, Level I trauma center. PARTICIPANTS: Consenting adults for limited
      pelvis CT. MAIN OUTCOME MEASUREMENTS: The three-dimensional anatomy of the
      posterior pelvic ring pertinent to S1 and S2 iliosacral screw placement. Safety
      of simulated S1 iliosacral screw placement using different lateral ilium starting
      points. RESULTS: The transversely placed (horizontal) iliosacral screw was the
      least safe of the screws tested. The safest lateral ilium starting point for our
      entire population was at the posterior sacral body sagittally and at the inferior
      S1 foramen coronally. S2 iliosacral screws had less cross-sectional area for
      placement than S1 screws. Placement of the S2 screw slightly to the S1 foraminal
      side of the S2 vertebral body increased the safety of placement. CONCLUSION: The
      iliosacral screw starting point at the posterior sacral body and inferior S1
      foramen was the safest when considering the entire population. Careful attention
      to the size and orientation of the S2 vertebral body should be taken if S2
      iliosacral screws are placed.

PMID- 10898200
TI  - Comminuted fractures of the iliac wing.
AB  - PURPOSE: Comminuted iliac fractures are uncommon and difficult to treat. The
      purpose of this study is to further delineate the fractures, to present a
      management protocol, and to evaluate the results of treatment. DESIGN:
      Retrospective clinical study. SETTING: Level one trauma center at Harborview
      Medical Center. PATIENTS: During a sixty-eight-month period, 695 patients with
      pelvic ring disruptions were treated at a level one trauma center. Thirteen
      (1.9%) of these patients had a severely comminuted iliac fracture. All patients
      were men, ranging in age from twenty to eighty years (mean, 38 years). These
      patients were polytraumatized and had a mean Injury Severity Score of 23. Eleven
      of the thirteen patients had severe iliac and flank degloving injuries. Five
      patients had open fractures, one with fecal contamination requiring diverting
      colostomy. Six patients with clinical signs of hemodynamic instability had local
      arterial injuries associated with their fractures. All five patients with
      extension of the fracture into the greater sciatic notch were found to have a
      local arterial injury on angiography. One patient had a lumbosacral plexopathy on
      the fractured side. Four patients had traumatic brain injuries. INTERVENTION: All
      thirteen patients were treated operatively. Routine pelvic external fixation was
      not possible because of the iliac comminution. Stable internal fixation was
      accomplished by an anterior iliac surgical exposure using lag screw and plate
      combinations. The open wounds and degloving injuries were treated with
      irrigation, debridement, and closed suction drainage. MAIN OUTCOME MEASUREMENTS:
      Healing and stability of fixation were assessed clinically and on pelvic
      radiographs. RESULTS: Comminuted iliac fractures were divided into two patient
      groups, according to associated pelvic ring disruption. Follow-up evaluations
      were available for all patients at a mean of eighteen months after injury. There
      were no deaths. All of the fractures healed clinically and radiographically. In
      one patient, fecal contamination caused a polymicrobial wound infection, and this
      patient had an associated delay in union of the fracture. Another patient with an
      open fracture developed a deep wound infection. Both infections responded to
      local management and antibiotics. There were no complications associated with the
      degloving injuries. CONCLUSIONS: Comminuted iliac fractures occur in two distinct
      patterns and are associated with numerous local injuries that complicate
      management. Management protocols should include early open reduction and stable
      internal fixation. Traumatic open wounds should not be closed primarily. Primary
      closure with closed suction drainage is effective in the management of associated
      degloving injuries. Extension of the fracture into the greater sciatic notch
      warrants further evaluation with pelvic angiography.

PMID- 10898201
TI  - Field hospital treatment of blast wounds of the musculoskeletal system during the
      Yugoslav civil war.
AB  - The spectrum of wounding and treatment of forty-one patients with musculoskeletal
      blast injuries at a U.S. military field hospital in the former Yugoslavia was
      reviewed. Patients underwent wound exploration, irrigation, debridement, broad
      spectrum antibiotic therapy, early fracture stabilization, and appropriate
      reconstructive surgery. Four patients developed wound infections. Two patients
      died as a result of their injuries (overall mortality 5 percent). There were
      three below-knee amputations and five other amputations (above-knee, ankle,
      midtarsal, partial forefoot, and finger). Three patients sustained lumbar burst
      fractures from mines that exploded under their vehicles, resulting in paraplegia
      in one case. Our patients underwent 112 surgical procedures, an average of 2.1
      per patient. Twenty-two patients (54 percent) had other injuries or conditions in
      addition to their orthopaedic wounds. There were wide variations in the bone and
      soft tissue injuries caused by detonating ordnance, and the tissue damage was
      qualitatively different from that caused by gunshot wounds. Early debridement,
      leaving wounds open, and treatment with broad-spectrum antibiotics were important
      factors in wound healing to allow subsequent successful reconstructive surgery in
      an austere field setting.

PMID- 10898203
TI  - Evaluation criteria list for trauma outcome.

PMID- 10898202
TI  - Facts about the disaster at Eschede.
AB  - On June 3, 1998, at 10:59 a.m., a high-speed train (Intercity Express, ICE)
      traveling at 200 kilometers per hour collided with a bridge at Eschede, Germany,
      causing it to collapse. The force of the collision, combined with the speed of
      the train's rear engine, propelled the rear wagons into the structure. The
      accident caused 101 deaths and 103 injuries. Four minutes after the accident, the
      alarm was reported; sixteen minutes after the accident, the first doctor on
      emergency call was on the scene, arriving from Celle, approximately twenty
      kilometers away. In the first four hours after the crash, different rescue
      organizations brought a total of 1,844 people to the accident site, including 461
      ambulance personnel and paramedics. Thirty-nine aircraft, including helicopters
      and army aircraft, were available at the scene. Ninety-five passengers passed
      away on site. Many of the surviving passengers had multiple injuries and were
      stuck in the train; although they had to be rescued from the severely damaged
      wagons, all patients, with one exception, were on the way to hospitals by 12:55
      p.m. The casualties were distributed among twenty-two hospitals; two victims
      later had to be transferred to other hospitals for medical reasons. This paper
      details the factors that were responsible for the success of the rescue
      operations at Eschede.

PMID- 10898204
TI  - Evaluation criteria list for trauma outcome: recommended by AO/ASIF.

PMID- 10898205
TI  - Severely displaced scaphoid fracture treated by arthroscopic assisted reduction
      and osteosynthesis.
AB  - The severely displaced scaphoid fracture, when combined with a scapholunate
      dissociation, is a very rare condition that commonly is treated by open surgery.
      The authors present a case treated by arthroscopic-assisted closed reduction,
      using percutaneous pinning for the scapholunate dissociation and a
      Herbert/Whipple screw insertion for the scaphoid fracture. The patient was able
      to return to work four months after surgery. At twenty-seven months after
      surgery, both the patient's grip power and range of motion in the wrist were
      acceptable. The authors recommend this procedure as a minimally invasive
      operation.

PMID- 10898206
TI  - Flexon-type Salter-Harris I injury of the proximal tibial epiphysis.
AB  - The authors report a case of a flexion-type epiphyseal separation of the proximal
      tibia. The injury described herein is a displaced Salter-Harris type I injury.
      Literature pertaining to this rare injury is reviewed, and management options are
      discussed.

PMID- 10898207
TI  - Isolated tibial shaft fracture.
AB  - A nineteen-year-old otherwise healthy woman is seen in the emergency room after
      being struck by a car. The patient reports left lower extremity pain and has no
      other injuries. Exam shows a Tscherne grade I soft tissue injury with otherwise
      normal motor and sensory exam. There are no signs of compartment syndrome. A
      closed reduction was performed.

PMID- 10898208
TI  - The time of ovulation in relation to estrus duration in gilts.
AB  - The objective of this study was to determine time of ovulation, monitored by
      transcutaneous ultrasonography, relative to the duration of estrus in gilts. We
      exposed 92 cyclic gilts, Camborough x Canabrid terminal line, at Day 19 of their
      third estrous cycle to vasectomized boars every 6 h for the detection estrus.
      Transcutaneous ultrasonography was performed every 6 h, starting 24 h after the
      onset estrus, to determine time of ovulation. Estrus duration was, on average,
      52.6 h (range: 30 to 72 h), and ovulation occurred between 30 and 60 h after the
      onset of estrus (mean: 44 h), about 85 % of the way through the estrus period.
      The time of ovulation during estrus was dependent on the duration of estrus (Time
      of ovulation = (duration of estrus) x 0.409 + 22.7; r = 0.57, P = 0.0001).
      Prediction of the time of ovulation in relation to duration of estrus is
      important for determining the optimal time for inseminating gilts. This knowledge
      would contribute to an improvement in the fertilization rate and in reproductive
      efficiency of the breeding herd.

PMID- 10898209
TI  - The influence of inhibited prostaglandin biosynthesis on post-ovulatory oviductal
      ova transport in sows.
AB  - Changes in prostaglandin and progesterone concentrations after ovulation seem to
      affect reproductive functions in the sow. The influence of lowered prostaglandin
      levels on ova transport velocity through the isthmus part of the oviduct, and on
      progesterone concentrations, was studied during the second estrus after weaning
      in thirteen purebred Yorkshire multiparous sows. To determine the time of
      ovulation transrectal ultrasonographic examination was performed. In the second
      estrus, six sows were given intravenous injections of flunixin meglumine (2.2
      mg/kg body weight) every sixth hour from 4 to 8 h after time of ovulation until
      about 48 h after ovulation, at which time the sows were slaughtered. Blood
      samples were collected every second hour from about 12 h before ovulation until
      slaughter. Progesterone and prostaglandin F2alpha (PGF2alpha) metabolite levels
      were determined. Immediately after slaughter the isthmus part of the oviducts
      were cut into 3 equally long segments and the number of ova in each segment, and
      in the upper part of the uterine horns, was determined. Before start of
      treatment, PGF2alpha metabolite levels were similar in the 2 groups (P=0.84). In
      the treatment group, PGF2alpha values dropped to below the detection limit
      immediately after start of treatment, whereas in the control group the
      concentrations were quite stable throughout the sampling period (P=0.005). Ova
      recovery rate was 94% in the treatment group and 95 % in the control group. At
      time of slaughter, in the treatment group ova had on average passed 2.1 segments
      whereas in the control group the ova had passed 2.5 segments (P=0.57). The
      progesterone levels increased continuously in both groups after ovulation but
      there was no difference in the mean progesterone concentrations between the two
      groups before (P=0.96) or after (P=0.58) ovulation. It can be concluded that the
      transport of ova through the isthmus part of the oviduct is unaffected by an
      inhibition of prostaglandin synthesis immediately after ovulation. Furthermore,
      the post-ovulatory progesterone profile seems unaffected by lowered PGF2alpha
      levels.

PMID- 10898210
TI  - Site of semen deposition in cattle: a review.
AB  - The breeding of cattle using conventional artificial insemination methods
      involves the deposition of semen in the uterine body. However, it has been
      recently proposed by several authors that the site of semen deposition be changed
      to the uterine horns. This suggestion is based on 2 facts: the acceptance that
      the major preovulatory sperm reservoir may be the uterotubal junction rather than
      the cervical canal, and the lack of accuracy by inseminators in depositing semen.
      In over 50% of cases, inseminators were not sufficiently trained to deposit semen
      into the uterine body, so that intracervical insemination was often performed
      resulting in reduced fertility. The advantage of deep uterine insemination,
      whether bicornual or unicornual, is that it favors the deposition of semen nearer
      to the uterotubal junction and thus reduces the incidence of cervical deposition.
      This review updates the literature on the ideal site of semen deposition,
      including cervical, uterine body, cornual and intraperitoneal. Also analyzed are
      the effects of right vs. left side activity of the female reproductive tract on
      the optimum site of semen deposition as it affects fertilization. Finally, the
      question of whether the clinical training of inseminators should be reevaluated
      is discussed.

PMID- 10898211
TI  - Hypoosmotic swelling (HOS) as a screening.
AB  - Semen from 5 Piedmontese bulls was subjected to the hypoosmotic swelling (HOS)
      test in order to determine if the results could be correlated to the fertilizing
      capacity in vitro. Semen was routinely prepared for in vitro fertilization (IVF),
      with aliquots being sampled after thawing, after separation on a Percoll gradient
      and after capacitation in a medium containing heparin. The aliquots were added to
      a fructose-sodium citrate hypoosmotic solution (100 mOsm) and incubated at 37
      degrees C for 5 min. At least 200 spermatozoa were observed at x 400 and
      classified according to the presence or the absence of a swollen tail. After
      capacitation, spermatozoa were used to fertilize in vitro-matured bovine oocytes
      (1.5 x10(6) cells/mL); IVF was performed in Fert-TALP medium supplemented with 6
      mg/mL BSA and 10 microL/mL heparin in a humidified atmosphere with 5% CO2 and 5%
      oxygen. Presumptive zygotes were cultured in SOF medium supplemented with 8 mg/mL
      BSA and amino acids. There were no significant differences in the in vitro
      fertility of the bulls, but a significant difference was found between bulls in
      the response to the HOS test. The 3 assays were significantly correlated, while
      no significant correlation was observed between the percentage of swollen
      spermatozoa and in vitro fertility. The HOS test does not appear to be
      sufficiently sensitive to discriminate between semen samples of intermediate
      fertility like those used in this preliminary research.

PMID- 10898212
TI  - Ovulation and follicular growth in gonadotropin-treated gilts followed by in
      vitro fertilization and development of their oocytes.
AB  - We investigated whether porcine ovaries derived from FSH-pituitary (FSH-P) or hCG
      treated animals can produce oocytes with better in vitro cytoplasmic maturation
      and in vitro embryonic development relative to those derived from saline-treated
      animals. The size of the follicle producing the oocyte was also studied. Each of
      25 prepubertal gilts received 1 of 6 treatments by intramuscular injection: 1)
      saline (3 mL, once, n = 5); 2) FSH-P8-3 (8 mg, 3 times, with a 24-h interval, n =
      4); 3) FSH-P16-3 (16 mg, 3 times, with a 24-h interval, n = 4); 4) FSH-P16-1-P4-2
      (16 mg, once, 4 mg, twice, with a 24-h interval, n = 4); 5) FSH-P16-1 (16 mg,
      once, n = 4); or 6) hCG (100 IU, 3 times, with a 24-h interval, n = 4). The
      ovaries were removed by mid-ventral laparotomy 72 h after the first injection.
      The numbers of corpora hemorrhagica (CH) with each FSH-P treatment were similar
      (P > 0.05). However, compared with gilts treated with saline or hCG, those
      treated with FSH-P8-3 had a greater (P < 0.05) number of CH. Treatment with FSH
      P8-3 or FSH-P16-3 induced significant growth of medium/large follicles (4 to 8 mm
      in diameter) compared with saline or FSH-P16-1. The same results were observed
      when FSH-P8-3 was compared with FSH-P16-P4-2 or hCG. After in vitro
      fertilization, the rates of male and female pronuclei in oocytes derived from
      medium/large follicles did not differ (P > 0.05) between treatments, but in
      oocytes derived from small follicles they were lower (P < 0.05) in saline-treated
      than in FSH-P16-1-P4-2-treated gilts. After 120 h in culture, the percentages of
      the inseminated oocytes from 1 to 3 mm or 4 to 8 mm follicles developing to > or
      = 2-cell did not differ (P > 0.05) between saline- and gonadotropin-treated
      gilts. However, a higher (P < 0.05) percentage of the inseminated oocytes from 4
      to 8 mm follicles had developed to the morula stage or beyond, than those from
      the 1 to 3 mm follicles. In conclusion, administration of single or multiple
      doses of FSH-P induced ovulation, but only 8 or 16 mg FSH-P injected 3 times with
      24-h intervals for 72 h induced growth of 4 to 8 mm follicles. The size of
      follicle from which the oocyte derived also had a significant effect on its
      development in vitro.

PMID- 10898213
TI  - Efficient cryopreservation of bovine blastocysts derived from nuclear transfer
      with somatic cells using partial dehydration and vitrification.
AB  - Preservation by vitrification of Day 7 and Day 8 bovine blastocysts derived from
      nuclear transfer with cumulus cells was compared with preservation of in vitro
      fertilized blastocysts. In Experiment 1, embryos were vitrified in PBS containing
      60% ethylene glycol. In Experiment 2, they were vitrified in combination with
      partial dehydration using a solution of 39% ethylene glycol + 0.7 M sucrose and
      8.6% Ficoll. In Experiment 1, survival and hatching rates were 44 and 95% for
      nuclear transferred embryos, and 78 and 55% for in vitro fertilized embryos,
      respectively. In Experiment 2, survival and hatching rates were 93 and 95% for
      nuclear transfer embryos, and 77 and 85% for in vitro fertilized embryos,
      respectively. It is concluded that Day 7 and Day 8 bovine blastocysts derived
      from cumulus cells could be cryopreserved without the loss of viability by a
      simple and efficient method using a combination of partial dehydration and
      vitrification.

PMID- 10898214
TI  - Production of mice derived entirely from embryonic stem cells after injecting the
      cells into heat treated blastocysts.
AB  - The sensitivity of the inner cell mass (ICM) and trophectoderm (TE) of mouse
      blastocysts to high temperatures was examined. When blastocysts with a diameter
      of 100 to 120 microm treated for 15 to 20 min at 45 degrees C were cultured in
      vitro, the cell number in the ICM did not increase, although that in the TE did
      increase. After transfer of treated blastocysts to recipients, implantation was
      not drastically inhibited but no live fetuses were obtained. These results
      demonstrated that the ICM at the blastocyst stage was more sensitive to high
      temperature than the TE. ICM clumps or ES cells were injected into blastocysts
      treated for 20 min at 45 degrees C. After transfer of injected blastocysts to
      recipients, we obtained mice derived completely from ICM or ES cells as judged by
      GPI analysis. Since 4 of 7 ES-cell derived mice, but none of the 6 mice derived
      from the ICM died after birth, an as yet unidentified epigenetic alteration might
      have occurred during the establishment and/or culture of ES cells.

PMID- 10898215
TI  - Compartmentalization of steroidogen esis by the equine corpus luteum.
AB  - The presence of cytochrome P450C17 within equine follicles and corpora lutea (CL)
      was detected by immunostaining. Two different antibodies were used which had
      previously been shown by immunoblotting to cross-react with equine P450C17.
      Strong positive immunostaining was present in the theca-derived cells of the CL
      during the estrous cycle and pregnancy. In the CL from mares after Day 40 of
      pregnancy there were also occasional bands of positively stained cells which
      resembled the polyhedral-shaped theca cells seen in preovulatory follicles. The
      pattern of immunostaining suggested compartmentalization of steroidogenesis
      within the equine CL with small cells possessing the potential to produce
      androgen which could then be aromatized to estrogen by the large luteal cells.

PMID- 10898216
TI  - Common egg envelope antigens are limited to the animal class.
AB  - The antigens of the egg envelope (zona pellucida) in mammals are of special
      interest because of their possible involvement in immunoinfertility and as
      candidate targets for immunocontraception. Conserved zona epitopes from divergent
      species may present a suitable source and an animal model for investigation of
      the above factors. We compared egg envelope antigens from 6 species of
      vertebrates belonging to 3 different classes in order to demonstrate the
      existence of shared antigens. Egg envelopes from the trout, carp, turtle, hen,
      duck and quail were isolated and heat-solubilized. They were tested with rabbit
      polyclonal antisera against carp, trout and duck egg envelopes by the enzyme
      linked immunosorbent assay. The results showed significant cross-reactions among
      egg envelopes of fish and birds. The examined solubilized preparations did not
      show cross-reactivity with egg envelopes from any other class, suggesting that
      divergent species did not share common egg envelope antigens, and that their use
      may not be appropriate in the investigation of immunoinfertility and
      immunocontraception in humans.

PMID- 10898217
TI  - Evaluation on sperm quality of freshly ejaculated boar semen during in vitro
      storage under different temperatures.
AB  - The purpose of this study was to assess the sperm quality of fresh ejaculated
      boar semen stored under different temperatures for up to 48 h in order to use the
      fresh semen efficiently. Spermatozoa were evaluated by 4 methods: Using trypan
      blue staining, the viability of spermatozoa stored at 39, 20, 15 and 4 degrees C
      for 48 h were 1.6, 46.9, 42.0 and 31.0%, respectively. Employing the hypoosmotic
      swelling test (HOST) showed 1.7%(39 degrees C), 28.7%(20 degrees C), 24.1%(15
      degrees C), and 20.1%(4 degrees C) coiled-tail spermatozoa following 48 h
      storage. With Coomassie blue staining, the rates of acrosome-intact spermatozoa
      stored for 48 h were 4.5%(39 degrees C), 35.3%(20 degrees C), 55.7%(15 degrees C)
      and 22.8%(4 degrees C). Using fluorescein isothiocyanate-peanut agglutinin (FITC
      PNA), the percentages of acrosome-intact spermatozoa stored for 48 h were 4.3%(39
      degrees C), 43.2%(20 degrees C), 17.3%(15 degrees C) and 14.8%(4 degrees C),
      respectively. The cytoplasmic droplets were found in 18.66% of the spermatozoa in
      fresh semen and were gradually shed during storage. The results of these 4
      methods were highly correlated and could be used to characterized sperm-cell
      quality effectively. These findings indicated that both membrane integrity and
      viability of spermatozoa could be preserved well during in vitro storage at 20
      degrees C and 15 degrees C for 24 to 48 h.

PMID- 10898218
TI  - Flow cytometric evaluation of antibiotic effects on viability and mitochondrial
      function of refrigerated spermatozoa of Nile tilapia.
AB  - Improved techniques for storage and evaluation of fish sperm would enhance
      breeding programs around the world. The goal of this study was to test the effect
      of antibiotics on refrigerated sperm from Nile tilapia (Oreochromis niloticus) by
      use of flow cytometry with 2 dual-staining protocols for objective assessment of
      sperm quality. Concentrations of 1 x 10(9). sperm/mL were suspended in Ringer's
      buffer at 318 mOsmol/kg (pH 8.0). The fluorescent stains Sybr 14 (10 microM),
      propidium iodide (2.4 mM), and rhodamine 123 (0.13 microM) were used to assess
      cell viability and mitochondrial function. Three concentrations of ampicillin,
      gentamicin, and an antibiotic/antimycotic solution were added to fresh
      spermatozoa. Motility estimates and flow cytometry measurements were made daily
      during 7 d of refrigerated storage (4 degrees C). The highest concentrations of
      gentamicin and antibiotic/antimycotic and all 3 concentrations of ampicillin
      significantly reduced sperm viability. The highest of each of the 3 antibiotic
      concentrations significantly reduced mitochondrial function. This study
      demonstrates that objective sperm quality assessments can be made using flow
      cytometry and that addition of antibiotics at appropriate concentrations can
      lengthen refrigerated storage time for tilapia spermatozoa. With minor
      modifications, these protocols can be adapted for use with sperm from other
      species and with other tissue types.

PMID- 10898219
TI  - Sexing of porcine embryo by in situ hybridization using chromosome Y- and 1
      specific DNA probes.
AB  - This study was carried out to determine if a rapid, simultaneous detection system
      using chromosome Y- and 1-bearing boar spermatozoa was applicable for sexing
      embryos. Porcine embryos were recovered from gilts and sows 4 to 6 d after
      mating, and whole embryos or biopsy cells were mounted on a glass slide with a
      small amount of fixative (methanol: acetic acid: distilled water = 9:1:4). The
      samples were then stained by means of a fluorescence in situ hybridization (FISH)
      procedure developed specifically for the detection of Y-bearing spermatozoa.
      Hybridization was performed using digoxigenin (dig)-labeled chromosome Y-
      specific DNA, and biotin-labeled chromosome 1-specific DNA sequences were
      detected as a signal of FITC and Texas Red on nucleus visualized DAPI-stain.
      Proportions of whole embryos labeled with chromosome 1-probe were 17 and 97% at
      the 3 to 16 and > or = 32 cell stage, respectively. Of the 93 biopsied embryos
      analyzed by FISH, 85 embryos (91%) could be accurately classified as male or
      female. Of the 65 biopsied embryos, 60 embryos (92%) had a clear blastocoele and
      a inner cell mass after 48 h of culture in vitro, and these embryos were
      evaluated as available embryos. One out of 4 recipient gilts which received sexed
      embryos at transfer farrowed 12 piglets of the expected sex. The results of this
      study demonstrated that porcine embryos at the > or = 32 cell stage can be sexed
      within 2 h using the FISH method. Moreover further development of the FISH
      technique could make it an effective tool for the study of early porcine embryos
      and for the control of porcine sex.

PMID- 10898220
TI  - Hypoxia-regulated gene expression in fetal wound regeneration and adult wound
      repair.
AB  - Fetal skin wounds heal scarlessly while adult wounds scar. Fetal wound healing
      occurs in a physiologically hypoxic environment whereas in adult wound healing,
      cells have to acutely adapt to hypoxia caused by locally impaired blood supply.
      We examined the expression of hypoxia-inducible factor 1 (HIF-1), a potent
      transcriptional regulator of oxygen-dependent genes such as vascular endothelial
      growth factor (VEGF), and transforming growth factor-beta (TGF-beta), a
      potentially HIF-1-regulated scarring cytokine, on fetal and adult responses to
      wounding. Incisional skin wounds were created in four sheep fetuses (twins served
      as controls) and two ewes at 100 days of gestation (term = 150 days). Fetal and
      adult wounds as well as non-wounded control tissues were harvested 2 days post
      wounding. Intraoperative arterial blood gas analyses and invasive subcutaneous
      pO2 measurements revealed that the fetuses were indeed hypoxic while the mothers
      were normoxic. Expression patterns of HIF-1alpha were investigated by Western
      blot analyses. HIF-1alpha expression in fetal wounds and fetal control skin was
      similar, whereas HIF-1alpha was only detected in adult wounds but not in adult
      control skin. Exposure of cultured fetal and adult dermal fibroblasts to hypoxia
      (1% O2) showed a marked induction of VEGF mRNA. In contrast, exposure of these
      cell types to hypoxia did not significantly affect TGF-beta1 mRNA expression in
      comparison to their normoxic controls. The presence of HIF-1alpha in fetal but
      not in adult normal skin indicates that HIF-1alpha might be involved in fetal
      skin development. Conversely, the upregulation of HIF-1alpha in adult but not
      early fetal wound repair might represent a pathway in the pathogenesis of
      scarring, since several growth factors overexpressed in, and associated, with
      scarring are hypoxia-inducible. Further studies need to be performed in order to
      identify hypoxia-regulated HIF-1alpha target genes involved in the pathogenesis
      of scarring.

PMID- 10898221
TI  - Evaluation of probiotic treatment in a neonatal animal model.
AB  - The clinical use of probiotic agents such as enteral Lactobacillus to enhance
      intestinal defense against potential luminal pathogens has been tested in vivo;
      however, an understanding of the mechanisms responsible for the observed
      protection is lacking. The purpose of this study was to evaluate the effects of
      Lactobacillus on bacterial translocation (BT) in a neonatal animal model. Newborn
      New Zealand white rabbit pups were enterally fed a 10% Formulac solution
      inoculated with or without a 10(8) suspension of ampicillin-resistant Escherichia
      coli K1 (E. coli K1A) and/or Lactobacillus casei GG (Lacto GG). Pups received
      either no bacteria (n = 10), Lacto GG (n = 8), E. coli K1A (n = 26), or a
      combination of Lacto GG and E. coli K1A (n = 33). On day 3, representative tissue
      specimens from the mesenteric lymph nodes (MLN), spleen (SPL), and liver (LIV)
      were aseptically harvested in addition to a small-bowel (SB) sample that was
      rinsed to remove luminal contents. The specimens were then cultured in organism
      specific media. Statistical analysis was by one-way ANOVA with P values less than
      0.05 considered significant. Neonatal rabbits receiving Lacto GG-supplemented
      formula exhibited a 25% decrease (P < 0.05) in small-bowel colonization by E.
      coli K1A. In addition, Lacto GG decreased the frequency of extraintestinal BT by
      46% (P < 0.05), 61% (P < 0.05), and 23%, respectively, in the MLN, SPL, and LIV.
      We have shown that enterally-administered Lacto GG decreases the frequency of E.
      coli K1A translocation in a neonatal rabbit model. These results may have
      significant implications for the treatment of BT and sepsis in the human neonate
      and provide a model for further studies.

PMID- 10898222
TI  - The hypoplastic heart in congenital diaphragmatic hernia: reduced expression of
      basic fibroblast growth factor and platelet-derived growth factor.
AB  - Newborn infants with congenital diaphragmatic hernia (CDH) still have high
      mortality. Recently, the possible role of a cardiac maldevelopment in the high
      mortality has been suggested. Human and animal studies have demonstrated that
      heart weight is significantly reduced in the presence of CDH. Basic fibroblast
      growth factor (bFGF) and platelet-derived growth factor (PDGF) are pleiotropic
      regulatory peptides that are expressed in myocardium in precise developmental and
      spatial programs. PDGF and bFGF both stimulate cardiac growth by inducing cell
      proliferation and stimulating the synthesis of extracellular matrix. The aim of
      this study was to investigate the presence of heart hypoplasia in nitrofen
      induced CDH in rats and the role of specific tissue growth factors (bFGF and
      PDGF) in its genesis. CDH was induced in pregnant rats following administration
      of 100 mg nitrofen on day 9.5 of gestation (term 22 days). In control animals the
      same dose of olive oil was given without nitrofen. Cesarean section was performed
      on day 21 of gestation. The fetuses were divided in two groups: normal controls
      (n = 8) and nitrofen-induced CDH (n = 8). Total RNA, DNA, and soluble proteins
      were extracted from the heart in each group and measured. mRNA was extracted from
      total RNA and a reverse transcription-polymerase chain reaction (RT-PCR) was
      performed to evaluate mRNA expression of bFGF and PDGF. The heart/body weight
      ratio (HBWR) and DNA content were significantly decreased (P < 0.01) in CDH
      animals compared to controls. RNA and protein content were also reduced in CDH.
      The expression of bFGF and PDGF mRNA was significantly reduced in the CDH group
      compared to controls (P < 0.01). The decreased HBWR, DNA, RNA, and protein
      content in the CDH heart indicates that the heart is hypoplastic in nitrofen
      induced left CDH. The downregulation of bFGF and PDGF gene expression in the CDH
      heart suggests that these regulating peptides may play an important role in the
      genesis of cardiac hypoplasia in CDH.

PMID- 10898223
TI  - Heparin and in-vitro experimental lung hypoplasia.
AB  - Pulmonary hypoplasia (PH) is a leading contributor to the lethality of congenital
      diaphragmatic hernia (CDH). Studies now suggest that PH arises prior to visceral
      herniation. Growth factors (GF) are pivotal to this embryonic lung growth. With
      striking in-vitro effects on lung morphogenesis, GF are under investigation as
      therapies for PH. Heparin modulates the kinetics of heparan-sulphate binding
      ligands that drive lung development. We hypothesised that heparin may rescue PH
      by favourable alteration of endogenous pulmonary GF activity. Normal and
      hypoplastic lung primordia were microdissected on day 13.5 of gestation and
      cultured for up to 78 h in plain media with and without heparin. In-vitro
      morphological development was studied by serial measurements of terminal bud
      count, lung area, and lung perimeter. Nitrofen-exposed lungs cultured with
      heparin showed no significant improvements in terminal bud count, lung area, and
      lung perimeter at 30, 54, and 78 h compared to untreated hypoplastic lungs
      maintained in vitro. In normal lungs heparin demonstrated no sustained
      significant morphological effects compared to untreated control lungs. In this
      study, heparin did not stimulate branching morphogenesis of normal or hypoplastic
      lungs in our organ culture system. Known at higher concentrations to inhibit
      smooth-muscle proliferation, heparin may ameliorate pulmonary vascular
      hypermuscularisation with the prospect of benefiting CDH infants on
      extracorporeal membrane oxygenation. Future studies will address the impact of
      exogenous GF on hypoplastic lung development in organ culture.

PMID- 10898224
TI  - Antenatal dexamethasone improves atrial natriuretic peptide receptors in
      hypoplastic lung in nitrofen-induced diaphragmatic hernia in rats.
AB  - Atrial natriuretic peptide (ANP) plays a major role in electrolyte and volume
      homeostasis through potent biological effects including vasorelaxation,
      bronchorelaxation, lung permeability, and clearance. There are two distinct
      biochemical and functional classes of ANP receptors, guanylate cyclase receptor
      (GC-R) and clearance receptors (clearance-R). Two subtypes of GC-R have been
      described, GCA-R and GCB-R. Antenatal glucocorticoid therapy (AGT) has been
      demonstrated to improve pulmonary immaturity and abnormal structure of pulmonary
      arteries in animal models of congenital diaphragmatic hernia (CDH). The aim of
      this study was to investigate the effect of antenatal glucocorticoid
      administration on the ANP system in nitrofen-induced CDH hypoplastic lung in
      rats. A CDH model was induced in pregnant rats following administration of
      nitrofen on day 9.5 of gestation. Dexamethasone (Dex) was given intraperitoneally
      on days 18.5 and 19.5; cesarean section was performed on day 21. Reverse
      transcription polymerase chain reaction was performed to evaluate the relative
      amounts of GCA-R, GCB-R and clearance-R mRNA expression. The mRNA expression of
      GCA-R, GCB-R, and clearance-R was significantly increased in CDH compared to
      control lung. ANP receptor mRNA expression was significantly decreased in CDH
      lung with compared to without Dex treatment. Our finding of increased ANP
      receptor mRNA expression in CDH lung suggests that the hypoplastic lung has high
      sensitivity for ANP. Decreased mRNA expression of ANP receptors in CDH lung after
      Dex treatment suggests that AGT may improve pulmonary physiological function of
      ANP in hypoplastic CDH lung.

PMID- 10898225
TI  - Defective epithelial-mesenchymal interactions dictate the organogenesis of
      tracheoesophageal fistula.
AB  - We have previously suggested that the fistula tract in esophageal atresia with
      tracheoesophageal fistula (EA/TEF) arises from a trifurcation of the embryonic
      lung bud. Thus, it appears to be a respiratory-derived structure, and expresses
      the lung-specific transcription factor TTF-1 in its epithelium. The fistula tract
      does not give rise to lungs like the other branches from the bud. It grows
      caudally until it fistulizes with the stomach. We hypothesized that epithelial
      mesenchymal interactions (EMI) dictate the differential pattern of growth of the
      respiratory-derived fistula tract in EA/TEF. EA/TEF was induced in rat embryos
      via prenatal exposure to adriamycin. Microdissection was performed on E13.5
      embryos to isolate developing lung bud, fistula tract, or esophagus from
      adriamycin-treated or control animals, respectively. The mesenchyme and
      epithelium from each of these foregut structures were separated. The individual
      epithelia were recombined with each of the various mesenchymes and grown in
      culture. They were assayed for relative degrees of branching. Isolated lung-bud
      epithelia (LBE) or fistula epithelium were also cultured in Matrigel with
      exogenous fibroblast growth factors (FGF) and subsequently assayed for branching.
      The fistula-tract mesenchyme relatively inhibited branching of lung epithelium.
      The epithelium of the fistula tract could be induced to branch by non-fistula
      (lung or esophageal) mesenchyme. The fistula-tract and adriamycin-treated LBE
      both branched in response to FGF1. In contrast, neither responded to FGF7 or
      FGF10. EMI are defective in the developing EA/TEF. The inability to respond to
      FGF7 and FGF10 suggests an epithelial defect involving the receptor FGF2R-IIIb,
      to which these mesenchymal factors obligately bind. Thus, the mesenchyme around
      the developing fistula tract may lack an FGF branching morphogen(s), such as
      FGF1. Hence, this mesenchyme is unable to induce branching of respiratory
      epithelia and allows the middle branch of the embryonic tracheal trifurcation to
      grow caudally as an unbranched tube until it fistulizes into the stomach.

PMID- 10898226
TI  - The effect of phospholipase A2 on bacterial translocation in a cell culture
      model.
AB  - The activity of phospholipase (PL)A2 is elevated in the intestinal epithelia of
      patients with inflammatory bowel disease (IBD). Recently, we reported that
      lysophosphatidylcholine (L-PC), the PLA2 hydrolysis product of
      phosphatidylcholine (PC), stimulates bacterial translocation (BT) in an
      enterocyte cell-culture model. These two observations stimulated us to examine
      the effects of extracellular PLA2 on intestinal epithelial permeability. Human
      Caco-2 enterocytes were grown to confluence on porous filters in the apical
      chamber of a two-chamber cell-culture system. Monolayer integrity and tight
      junction permeability were measured by dextran blue (DB) permeability and
      transepithelial electric resistance (TEER). Monolayers were treated with PC, L
      PC, or PLA2 with and without PC. The magnitude of BT was determined 2 h after
      treatment by adding Escherichia coli to the apical chamber followed by
      quantitatively culturing basal chamber samples. Thin-layer chromatography (TLC)
      was utilized to verify PLA2 hydrolysis of PC to L-PC. Statistical analysis was
      performed by one-way analysis of variance. The magnitude of BT across monolayers
      pretreated with PLA2 + PC significantly increased compared to either PC or PLA2
      (6.83 +/- 0.069, 2.41 +/- 0.46, and 3.06 +/- 1.14 log10 colony forming units/ml,
      respectively, P < 0.05). Absence of DB-permeability in any group confirmed
      monolayer integrity. TLC of PL samples harvested from the apical monolayer
      surface confirmed PC hydrolysis. PLA2 mediates hydrolysis of PC to L-PC when both
      are applied to the apical surface of cultured enterocyte monolayers, resulting in
      increased BT and increased TEER with no damage to monolayer integrity. These
      observations may have implications in the pathogenesis and treatment strategies
      for IBD.

PMID- 10898227
TI  - Muscarinic acetylcholine receptor expression in aganglionic bowel.
AB  - In Hirschsprung's disease (HD) there exists an overabundance of acetylcholine
      (ACh), which in turn stimulates excessive production of the enzyme
      acetylcholinesterase. Muscarinic ACh receptors (mAChRs) play an important role in
      smooth-muscle contraction. Recent studies have indicated five different subtypes
      of mAChRs encoded by five different genes, ml to m5. The purpose of this study
      was to investigate the expression of each mAChR subtype in aganglionic (AG) colon
      to further understand the pathophysiology of HD. Entire colon resected at the
      time of pull-through operation for HD was obtained from 14 patients. Specimens
      obtained at autopsy from 8 age-matched patients without gastrointestinal disease
      acted as controls. Frozen sections were used for indirect immunohistochemistry as
      well as in-situ hybridization. Immunohistochemistry was performed using specific
      antiserum against each mAChR subtype and in-situ hybridization was performed
      using specific oligonucleotide probes against ml to m5 subtypes. Messenger RNA
      (mRNA) was extracted from normoganglionic (NG) and AG bowel of HD patients and
      normal control bowel. Reverse transcription-polymerase chain reaction was
      performed to evaluate mRNA levels of each mAChR subtype. To adjust the levels of
      mRNA expression, a housekeeping gene G3PDH, known to be expressed normally, was
      used as an internal control. Strong m2 and m3 immunoreactivity was observed in
      the mucosal layer, smooth-muscle layers, and myenteric plexus of NG bowel,
      whereas ml immunoreactivity was only detected in the mucosal layer. The most
      striking finding was the abundance of m3-immunoreactive fibers in muscle layers
      of NG bowel while there was a total lack of m3 fibers in smooth-muscle of AG
      bowel. Intense mRNA signals encoding m2 and m3 and to a lesser degree ml were
      detected in NG bowel, and these signals were weak in AG bowel. Immunoreactivity
      and mRNA expression of m4 and m5 was not detected in NG or AG bowel. The lack of
      m3-immunoreactive fibers in the smooth-muscle layers of AG bowel and decreased m2
      and m3 mRNA expression in AG bowel may be responsible for the motility
      dysfunction in the aganglionic segment.

PMID- 10898228
TI  - Survival of neurons and interstitial cells of Cajal after autotransplantation of
      myenteric ganglia from small intestine in the lethal spotted mouse.
AB  - To avoid mutilating surgery in the treatment of distal aganglionosis,
      transplantation of autologous nervous elements to the affected intestine would be
      an attractive option. This treatment modality has emerged as a possible
      alternative for different brain disorders, mostly using fetal nervous tissue. Our
      objective was to evaluate whether myenteric ganglia (MG) and interstitial cells
      of Cajal (ICC) could survive a transplantation procedure and to evaluate possible
      differences between animals with distal colonic aganglionosis (lethal spotted
      mice) and their healthy littermates. Autologous transplantation of MG with
      adherent smooth muscle from small intestine to the subcapsular space of the
      kidney was performed in mice 3-12 weeks of age. The transplants were evaluated 5
      to 9 days postoperatively. The presence of myenteric neurons in the transplants
      was registered using immunohistochemical detection of different neurotransmitters
      and markers. For identification of ICC antibodies against c-kit, a cell surface
      tyrosine-kinase receptor, were used. The transplants showed overall good
      survival. Neurons containing the general neuronal marker protein gene-related
      product, the neuronal nitric oxide synthesizing enzyme, and the neuropeptides
      vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide,
      calcitonin gene-related peptide, galanin, substance P, and neuropeptide Y could
      be shown throughout the transplants. ICC were consistently seen in the grafted
      tissue among the smooth muscle cells, particularly in the deep muscular plexus,
      and within the MG. No obvious differences in ICC or enteric neuronal tissue
      survival, or in the frequency of the various neuronal populations displayed could
      be detected between the two groups of animals. These findings support the use of
      autologous MG for further research on transplantation of enteric ganglia as a
      possible alternative treatment for colonic aganglionosis.

PMID- 10898229
TI  - The innervation of human bowel mucosa and its alterations in Hirschsprung's
      disease using a whole-mount preparation technique.
AB  - The innervation of the human bowel wall and its structural and functional changes
      in Hirschsprung's disease (HD) are well-recognised. The luminal surface of the
      bowel acts as a multifunctional barrier, and modifications in its physiochemical
      properties can result in serious complications such as enterocolitis (EC). The
      whole-mount preparation (WMP) technique produces a three-dimensional (3D) picture
      to better demonstrate the neuronal networks and the relationship of branching and
      interconnecting nerve fibres to each other. The aim of this study was to
      investigate the innervation of the mucosal layer in normal and HD bowel using a
      WMP immunohistochemistry technique in order to better understand the
      pathophysiology of HD. Full-thickness bowel specimens were collected from 9 HD
      patients at pull-through operation. Normal control small- and large-bowel
      specimens were collected from 10 patients at the time of bladder augmentation.
      Suction rectal biopsies from 8 patients with chronic constipation and 2 patients
      with HD were also included in this study. A WMP of the mucosal layer was made and
      stained with various neuronal markers (S100, PGP 9.5, and LICAM) using
      fluorescein immunohistochemistry. PGP 9.5, S100, and L1CAM immunofluorescence
      staining of the normal mucosa demonstrated a characteristic 3D meshlike neuronal
      network of uniform thickness surrounding the crypts. In the aganglionic bowel
      S100, PGP 9.5, and L1CAM-positive meshlike networks were replaced by thick nerve
      trunks in the muscosa without any interconnecting network. The present study
      demonstrates for the first time the 3D morphology of mucosal innervation in
      normal and aganglionic bowel. The WMP technique clearly demonstrated that the
      mucosal innervation in HD is morphologically abnormal, and this may adversely
      influence secretory and absorptive functions of the bowel. WMPs using suction
      rectal biopsy specimens may be a useful additional technique to diagnose HD.

PMID- 10898230
TI  - Structural immaturity of the pylorus muscle in infantile hypertrophic pyloric
      stenosis.
AB  - Recent reports indicate that extracellular matrix and cytoskeleton plasmalemmal
      elements are altered in infantile hypertrophic pyloric stenosis (IHPS). Desmin is
      a cytoskeletal protein that is important for the organization and function of
      muscular fibers. It has been found to be increased in the smooth muscle in
      chronic intestinal pseudo-obstruction and in skeletal muscle in some forms of
      myopathies as well as in unexplained hypertrophic cardiomyopathies. The aim of
      this study was to analyze the expression of desmin in IHPS. Full-thickness muscle
      biopsy specimens were obtained from 8 IHPS patients (age range 23 to 41 days) at
      pyloromyotomy, from 8 age-matched controls without evidence of gastrointestinal
      (GI) disease at autopsy, and from 2 stillborns who died at 27 and 30 weeks of
      gestation without evidence of GI disease. Indirect immunohistochemistry was
      performed using the avidin-biotin-peroxidase complex method with anti-desmin and
      visualized by development with 3-diaminobenzidine tetrahydrochloride. Pyloric
      muscle in IHPS demonstrated strong desmin immunoreactivity. The expression of
      desmin was also strong in the muscular layers of fetal pylorus. In the age
      matched controls absent or weak desmin immunoreactivity was seen in the pyloric
      muscle layer. The increased amount of desmin in hypertrophied pyloric muscle in
      IHPS may result in inco-ordination of contraction and relaxation of the pylorus,
      thus causing motility dysfunction. The similar pattern of desmin expression in
      IHPS and fetal pylorus suggests that the organization of intermediate filaments
      in IHPS is in a fetal stage of development.

PMID- 10898231
TI  - Organ-specific distribution of major histocompatibility antigens in rats.
AB  - The present study systematically investigated the expression and distribution of
      the major histocompatibility complex (MHC) classes I and II in the rat. About 150
      native tissue probes from eight adult Lewis rats were taken, representative for
      most organs, tissues, and the vascular system. MHC expression was analyzed by two
      monoclonal antibodies (mAb) generated against the non-polymorphic determinants of
      rat MHC class I (Ox-18) and class II (Ox-6). Immunoreactivities were compared to
      those of different endothelial (HIS52, TLD-3A12, Ox-43, REHA-1 antigen),
      histiocytic (ED1, ED2), B-cell (RLN-9D3), and T-cell (MRC Ox-52) markers. A
      nonspecific mAb (MR12/53) served as a negative control. Pretested concentrations
      on various tissues and the alkaline phosphatase-anti-alkaline phosphatase
      technique allowed semiquantitative evaluation of serial cryostat tissue sections.
      MHC class I expression was detected on most immunocompetent cells. Endothelial
      cells were stained heterogeneously along the vascular system and the organ
      specific microcirculation. Furthermore, some organs showed staining of
      parenchymal cells. MHC class II was found on all immunocompetent cells positive
      for the B-cell marker and about 15% of cells positive for the histiocytic
      markers. Besides the well-known expression of MHC class II in the outer zone of
      the renal proximal tubule, further organ-specific cell forms were found positive.
      In conclusion, the present study outlines tissue-specific distribution of MHC I/
      II and implies that each organ carries a variable immunologic burden that needs
      to be considered for any transplantation model.

PMID- 10898232
TI  - Proliferation, zonal maturation, and steroid production of fetal adrenal
      transplants in adrenalectomized rats.
AB  - The present study investigated the histologic maturation, proliferative capacity,
      and steroid production of fetal adrenal transplants (Tx) in adrenalectomized
      rats. A pair of fetal adrenal glands (18-20 days of gestation) was transplanted
      into the omentum of syngeneic Lewis rats (n = 45). Four weeks later, in 5 animals
      the grafts were excised for morphologic evaluation. Proliferation was
      investigated by immunohistochemical staining for KI-67 protein and quantified by
      the proliferation index (PI = positive cells/100 counts). All other hosts (Tx; n
      = 40) underwent bilateral adrenalectomy (AE) to induce Addisonian crisis.
      Postoperatively, survival and concentrations of potassium, sodium, aldosterone,
      and corticosterone were recorded for 6 months. These data were compared to
      controls (C=only AE; n = 30) and a sham group (S; n = 10). At the end of the
      study period all surviving hosts were killed for histologic examination of
      grafts. At 4 weeks post-Tx the adrenal grafts demonstrated a distinct zona
      glomerulosa and frequent proliferation with a PI of 0.084, comparable to normal
      control (0.092). Following AE survival was significantly prolonged in Tx (86% vs
      12% of C, P < 0.05). Control animals developed severe hyponatremia and
      hyperkalemia, whereas in Tx only transient signs of Addisonian crisis were
      recorded. Levels of aldosterone dropped within 7 days in the Tx and C groups, but
      returned to normal for Tx within 8 weeks. Corticosterone levels of Tx animals
      fell to 25% within week, but steadily increased to 70% by the end of the study.
      At 6 months, grafts revealed a mature adrenocortical structure with little
      proliferative activity, which was comparable to controls. In a syngeneic rat
      model fetal adrenal transplants thus mature and proliferate to provide sufficient
      steroid production for adrenalectomized hosts.

PMID- 10898233
TI  - The impact of hepatic xanthine oxidase and xanthine dehydrogenase activities on
      liver function in chronic cholestasis.
AB  - Activities of hepatic xanthine oxidase (XO) and xanthine dehydrogenase (XD),
      serum liver enzymes, and reduced glutathione (GSH) were determined in livers of
      chronic cholestatic rats. The common bile duct was ligated (CBDL) and rats were
      randomized to either an untreated group or to treatment with allopurinol, a
      competitive XO inhibitor, or received a tungsten-supplemented diet to inactivate
      XO and XD, or received antioxidants vitamin C and vitamin E. One group underwent
      only sham laparotomy. After 4 weeks, in untreated CBDL animals serum aspartate
      aminotransferase and bilirubin concentrations were significantly elevated and
      hepatic GSH was significantly decreased when compared with the sham-operated
      group. Histochemical and enzymatic determinations of XD and XO showed a
      significant increase in hepatic XO activity after CBDL. Treatment with
      allopurinol and a tungsten-supplemented, molybdenum-free diet significantly
      attenuated serum liver enzymes, hepatic XO activity, and improved hepatic GSH
      levels, whereas vitamins C and E had a positive effect only on hepatic GSH
      levels. Our results support the hypothesis that cholestasis-induced
      hepatocellular injury is partially triggered by oxidative processes derived from
      increased hepatic XO activity. Inhibition and inactivation of XO exerts a
      hepatocellular protective effect in chronic cholestasis.

PMID- 10898234
TI  - alpha-Glutathione-s-transferase as a new sensitive marker of hepatocellular
      damage in biliary atresia.
AB  - Early identification of patients likely to deteriorate post-hepatic
      portoenterostomy for biliary atresia (BA) would be beneficial. alpha-Glutathione
      s-transferase (alpha-GST) is a serologic marker of reactive hepatocellular damage
      because of its low molecular weight, uniform hepatic distribution, high cytosol
      concentration, and short half-life. We evaluated whether serum alpha-GST in post
      surgical BA patients correlates with liver function (LF) and investigated its
      potential as a medium- to long-term marker of prognosis. Postoperative BA
      patients (n = 30; mean age: 11.8 +/- 3.7 years) were divided into three groups
      based on average LF over the 3 months prior to this study. Group I (n = 8) were
      jaundice-free and had normal LF. Group II (n = 12) had moderate liver
      dysfunction, and group III (n = 10) had severe liver dysfunction. Serum alpha-GST
      was determined using a specific ELISA. Tissue alpha-GST was determined
      immunohistochemically, using liver needle-biopsy specimens. Bile lakes were found
      in 5 group II patients and 5 group III patients. Serum alpha-GST was
      significantly higher in group II (20.7 +/- 8.4 ng/ml) than in groups I (4.7 +/-
      1.3 ng/ml) and III (8.0 +/- 1.2 ng/ml) (P < 0.0001) and was highest in group II
      subjects with bile lakes. In control liver specimens alpha-GST distribution was
      weak but uniform throughout normal liver lobule hepatocytes. In group II there
      was strong staining in centrilobular hepatocytes, and in group III alpha-GST was
      only found in regenerative nodules. We conclude that alpha-GST may be a more
      sensitive indicator of hepatocellular damage in BA because its distribution is
      correlated to the proportion of functioning liver tissue present. This is the
      first report of this relationship, which has great implications for group II
      subjects because a sudden shift in concentration of alpha-GST may be a better
      predictor of impending hepatic dysfunction than conventional LF tests.

PMID- 10898235
TI  - Increased expression of fibroblast growth factors in segmental renal dysplasia.
AB  - Renal dysplasia (RD) is a disorganized development of renal parenchyma that
      results in a deficit of functional renal tissue. Dysplastic renal tissue is
      characterized by primitive tubular epithelium associated with increased
      mesenchyme. Several polypeptide growth factors (GF), which interact with target
      cells through a cell-surface membrane receptor, have been reported to be involved
      in the regulation of urothelial cell growth in normal and neoplastic states.
      Recent reports have demonstrated that basic fibroblast GF (bFGF, FGF-2) is a
      mitogen for renal proximal-tubule epithelial cells. Keratinocyte GF (KGF, FGF-7),
      which belongs to the FGF family, is believed to be a paracrine mediator of
      epithelial-cell proliferation. The aim of this study was to investigate the
      immunoactivity of bFGF and KGF and their receptors in the dysplastic kidney in
      order to further understand the pathogenesis of RD. Specimens of dysplastic upper
      poles of duplex kidneys were surgically resected from ten patients. Age-matched
      control material included six kidney specimens taken at autopsy from patients
      without evidence of urologic disease. Indirect immunohistochemistry was performed
      using the Strept-ABC method with four antibodies: bFGF, KGF, FGF receptor (flg),
      and KGF receptor (bek). There was absent or weak bFGF, KGF, flg, and bek
      immunoreactivity in normal kidneys. In the dysplastic kidneys, there was strong
      immunoreactivity of bFGF and KGF and their receptors in the epithelium of
      primitive tubules. Increased local expression of bFGF and KGF and their receptors
      in primitive tubules suggests that bFGF and KGF may play an important role in the
      development of RD.

PMID- 10898236
TI  - Report of the Advisory Council on Optical Technologies.

PMID- 10898237
TI  - Interaction between tissues and implantable materials.
AB  - Interaction between tissues and implantable materials is a factor of critical
      importance in biocompatibility studies. Bioactivity of implants is expected when
      the resorption or controlled integration of the implant with surrounding tissues
      is required. On the contrary, biomaterial inertness is suitable in the case of
      most load-bearing implants. Both desired and undesired consequences of partial
      implant biodegradation are discussed on the base of the authors' experimental
      work done on alumina and carbon-fiber-reinforced carbon composites (CFRC). Two
      examples of investigations of the interaction between bioceramics (CFRC, alumina,
      hydroxyapatite, and tricalcium phosphate) and cells in culture are shown as an
      alternative to the methods based on experimental implantation. The future of
      research on biomaterial-tissue interaction is discussed with respect to the
      developments in tissue engineering.

PMID- 10898238
TI  - New polymeric biomaterials-phospholipid polymers with a biocompatible surface.
AB  - New biomedical polymers were designed with attention to the surface of biological
      membranes, i.e. the surface was completely covered with phospholipid polar
      groups. The polymers with a phosphorylcholine group, 2-methacryloyloxyethyl
      phosphorylcholine (MPC) co-polymerized with hydrophobic alkyl group, could
      interact with phospholipids in plasma selectively and strongly. The adsorbed
      phospholipids on the polymer surface were concentrated, organized each other and
      then formed a self-assembled biomimetic membrane surface. The surface showed
      excellent resistance for both protein adsorption and blood cell adhesion, i.e.
      the MPC polymer showed good blood compatibility. Based on these characteristics
      of the MPC polymer, it was applied to improve the biocompatibility and
      biostability of an implantable glucose sensor. The relative output current of the
      sensor covered with the MPC polymer membrane was maintained as the initial level
      even after 14 days of subcutaneous implantation in a rat. Therefore, it is
      concluded that the MPC polymer membrane is an excellent material for implantable
      biomedical devices.

PMID- 10898239
TI  - Super-elastic property of Ti-Ni alloy for use in dentistry.
AB  - The super-elasticity of Ti-Ni alloy was investigated in tensile and bending tests
      to evaluate the mechanical properties of the castings and heat treatment effect
      on the bending properties of the wires for new clinical applications of the alloy
      in prosthodontics and orthodontics. In terms of the tensile properties of the
      castings, apparent proof stress increased and elongation decreased with the small
      increase in nickel content or with the decrease in titanium purity. This result
      suggests that precise control of the materials is indispensable to utilize the
      super-elasticity in dental cast appliances. In terms of the bending properties of
      Ti-Ni alloy wires, low residual deflection and small load/deflection ratio were
      obtained by the second heat treatment between 733 and 813 K, which was found to
      be suitable for the shape memory treatment of orthodontic appliances. Moreover,
      the functional force was changeable within this treatment temperature range.

PMID- 10898240
TI  - Kinetic modeling of fluid and solute transport in peritoneal dialysis.
AB  - Mathematical models for fluid and solute transport during peritoneal dialysis are
      described. A model for the transport of the so-called volume marker enables the
      correct estimation of the kinetics of the intraperitoneal dialysate volume as
      well as the rate of peritoneal fluid absorption. On the basis of these
      estimations, the solute transport components (diffusion, convective solute
      transport with ultrafiltrate and peritoneal solute absorption) may be separated
      within the net solute transport using a modified version of the Babb-Randerson
      Farrell (BRF) model. The diffusive mass transport coefficient and sieving
      coefficient are given by the model. A simplified method for the estimation of the
      diffusive mass transport coefficient during the so-called isovolemia period is
      also described and compared to the BRF modeling. The three-pore model and the
      distributed model, which describe the structure-function relationship for the
      peritoneum, are also addressed.

PMID- 10898241
TI  - Dialysis membranes for blood purification.
AB  - All of the artificial membranes in industrial use, such as a reverse-osmosis
      membrane, dialysis membrane, ultrafiltration membrane, microfiltration membrane
      and gas separation membrane, also have therapeutic applications. The most
      commonly used artificial organ is the artificial kidney, a machine that performs
      treatment known as hemodialysis. This process cleanses the body of a patient with
      renal failure by dialysis and filtration, simple physicochemical processes.
      Hemodialysis membranes are used to remove accumulated uremic toxins, excess ions
      and water from the patient via the dialysate, and to supply (deficit)
      insufficient ions from the dialysate. Dialysis membranes used clinically in the
      treatment of patients with renal failure account for by far the largest volume of
      membranes used worldwide; more than 70 million square meters are used a year.
      Almost all dialyzers now in use are of the hollow-fiber type. A hollow-fiber
      dialyzer contains a bundle of approximately 10000 hollow fibers, each with an
      inner diameter of about 200 microm when wet. The membrane thickness is about 20
      45 microm, and the length is 160-250 mm. The walls of the hollow fibers function
      as the dialysis membrane. Various materials, including cellulose-based materials
      and synthetic polymers, are used for dialysis membranes. This paper reviews blood
      purification, hemodialysis and dialysis membranes.

PMID- 10898242
TI  - Blood purification by a membrane technique--a new method for the effective
      removal of low-density lipoprotein cholesterol.
AB  - A membrane plasma fractionation (MPS) technique is applied in order to obtain
      selective removal of pathological plasma components from the extracorporeal
      circuit. An effective plasma fractionation procedure should be characterized by
      the highest possible removal of the pathological plasma components and, equally
      as important, the lowest unwanted protein losses caused mainly by adsorption to
      the membrane structure. In order to obtain a higher efficiency of the MPS
      procedure (high selectivity between removal of pathological plasma components and
      unwanted losses mainly represented by albumin) several methods such as
      thermofiltration, application of pulsate flow at the end of secondary filter,
      etc. have been developed. Clinical verification of these methods led to some
      improvement in MPS procedure but these results did not seem to be optimal. The
      main objective of this paper is to present a new two-stage membrane system
      utilizing a high flow recirculation circuit developed particularly, but not only,
      for effective removal of low-density lipoprotein cholesterol. The designed and
      developed system has been tested in vitro using several different plasma
      fractionation membranes. The results obtained indicated the importance of the
      membrane structure and membrane material on the efficiency of the tested plasma
      fractionation procedure. It was also found that it is possible to obtain
      negligible protein losses for some selected membrane structures applied in the
      assessed system. Based on preliminary results, it seems that the new two-stage
      membrane system proposed could be characterized by a very low range of unwanted
      protein losses leading to high effectiveness of the plasma fractionation
      procedure.

PMID- 10898243
TI  - Urea biosensors and their application in hemodialysis--perspective of EnFET
      application.
AB  - Parameters such as blood urea nitrogen concentration, normalized protein
      catabolic rate and Kt/V that are utilized for urea concentration measurements in
      blood and dialysate for the optimization of the hemodialysis process are reviewed
      in the paper. Basic methods of urea concentration measurement are described. Urea
      biosensors of the EnFET type based on the pH-sensitive Si3N4 gate FET and pNH4
      sensitive FET with a Siloprene membrane containing nonactine, both of our own
      construction, are presented. Application of these biosensors for urea
      concentration measurement in blood and dialysate is described. An experimental
      microdialysis system with urease in detector solution and a pH-ISFET detector are
      described. A comparison of two dialysis procedures, with a commercial dialysate
      an initial of pH 5.6 and with pH kept lowered during the dialysis process applied
      to rats, is given.

PMID- 10898244
TI  - Preliminary study of continuous glucose monitoring with a microdialysis technique
      and a null method--a numerical analysis.
AB  - Monitoring of the subcutaneous tissue glucose concentration is an attractive
      method for continuous monitoring of the glucose concentration in diabetic
      patients. Several researchers have studied this, but no satisfactory method has
      been developed. We have proposed a new method, which can measure the glucose
      concentration of subcutaneous tissue continuously, even as the efficiency of
      membrane perfusion and sensor performance decline. Two reference solutions were
      prepared with concentrations higher and lower than the objective solution. They
      were perfused alternately for different ratios of perfusion times. The glucose
      concentration, after perfusing microdialysis, was detected and the trend of
      changes in the concentration was used to control the ratio of the two perfusion
      solutions. When the trend was a unity, the glucose concentration was calculated
      from the ratio of the two perfusion solutions. The numerical study was performed
      with a compartment model and a basic control theory. In simulation, the 90%
      response time to step change was approximately 7 min, which is fast enough when
      compared with the fluctuation of glucose in the electrolyte. This result
      suggested that this new system might be useful for continuous monitoring of the
      glucose concentration in subcutaneous tissue.

PMID- 10898245
TI  - Genes and longevity: lessons from studies of centenarians.
AB  - In population studies of aging, the data on genetic markers are often collected
      for individuals from different age groups. The idea of such studies is to
      identify "longevity" or "frailty" genes by comparing the frequencies of genotypes
      in the oldest and in the younger groups of individuals. In this paper we discuss
      a new approach to the analysis of such data. This approach, based on the maximum
      likelihood method, combines data on genetic markers with survival information
      obtained from standard demographic life tables. This method allows us to evaluate
      survival characteristics for individuals carrying respective candidate genes. It
      can also be used in the estimation of the effects of allele-area and allele
      allele interaction, either in the presence or absence of hidden heterogeneity. We
      apply this method to the analysis of Italian data on genetic markers for five
      autosomal loci and mitochondrial genomes. Then we discuss basic assumptions used
      in this analysis and directions of further research.

PMID- 10898246
TI  - Increase in basal level of Hsp70, consisting chiefly of constitutively expressed
      Hsp70 (Hsc70) in aged rat brain.
AB  - Alteration of proteins in the function and higher structure has been observed in
      aged organisms. Stress proteins, which have a role to protect proteins from
      denaturation, may respond to the protein denaturation with aging. We found that
      the basal level of Hsp70, consisting chiefly of constitutively expressed Hsp70
      (Hsc70), in 24-month-old Wistar rats was significantly higher in some parts of
      the brain than that in 6-month-old rats. On the other hand, the basal level of
      Hsp70 was significantly lower in 24-month-old rats after restricted feeding,
      which is known to suppress aging, than those fed the diet ad libitum. In the
      pons, medulla, striatum, and thalamus of 24-month-old rat brain, the level of
      Hsp70 increased and the denaturation of the cytosol proteins was suppressed.
      These results suggest that the expression of Hsp70, mostly Hsc70, increases with
      aging and may have a role to suppress protein denaturation.

PMID- 10898247
TI  - Effects of high-intensity resistance training on untrained older men. I.
      Strength, cardiovascular, and metabolic responses.
AB  - Most resistance training studies of older subjects have emphasized low-intensity,
      short-term training programs that have concentrated on strength measurements. The
      purpose of this study was, in addition to the determination of strength, to
      assess intramuscular and transport factors that may be associated with strength
      increments. Eighteen untrained men ages 60-75 years volunteered for the study; 9
      were randomly placed in the resistance-training group (RT), and the other half
      served as untrained (UT) or control subjects. RT subjects performed a 16-week
      high-intensity (85-90% 1 repetition maximum (RT]) resistance training program (2
      x/wk) consisting of 3 sets each to failure (6-8 repetitions based on 1 RM of 3
      exercises): leg press (LP), half squat (HS), and leg extension (LE) with 1-2
      minutes rest between sets. Pre- and post- training strength was measured for the
      3 training exercises using a 1 RM protocol. Body fat was calculated using a 3
      site skinfold method. Biopsies from the vastus lateralis m. were obtained for
      fiber type composition, cross-sectional area, and capillarization measurements.
      Exercise metabolism, electrocardiography, and arterial blood pressure were
      observed continuously during a progressive treadmill test, and resting
      echocardiographic data were recorded for all subjects. Pre- and post-training
      venous blood samples were analyzed for serum lipids. Resistance training caused
      significant changes in the following comparisons: % fat decreased in the RT group
      by almost 3%, strength improved for all exercises: LE = + 50.4%, LP = + 72.3%, HS
      = + 83.5%; type IIB fibers decreased and IIA fibers increased; cross-sectional
      areas of all fiber types (I, IIA, IIB) increased significantly, and capillary to
      fiber ratio increased but not significantly. No differences were noted for ECG
      and echocardiographic data. The RT group significantly improved treadmill
      performance and VO2max. Pre- and post-training serum lipids improved but not
      significantly. No significant changes occurred in any pre- to post-tests for the
      UT group. The results show that skeletal muscle in older, untrained men will
      respond with significant strength gains accompanied by considerable increases in
      fiber size and capillary density. Maximal working capacity, VO2max, and serum
      lipid profiles also benefited from high-intensity resistance training, but no
      changes were observed for HR max, or maximal responses of arterial blood
      pressure. Older men may not only tolerate very high intensity work loads but will
      exhibit intramuscular, cardiovascular, and metabolic changes similar to younger
      subjects.

PMID- 10898248
TI  - Effects of high-intensity resistance training on untrained older men. II. Muscle
      fiber characteristics and nucleo-cytoplasmic relationships.
AB  - During growth and repair of skeletal muscle fibers, satellite cells become
      activated, undergo mitosis, and a daughter nucleus becomes incorporated into the
      muscle fiber to increase myonuclear numbers. An increase in myonuclei appears to
      be required for this postnatal growth. This study examined whether muscle fibers
      of elderly men can hypertrophy with strength training and, if so, whether they
      have the capacity to incorporate nuclei into the fibers. The sarcoplasmic area
      associated with each myonucleus was calculated in nine elderly men before and
      after 16 weeks of strength training, and compared to nine elderly control men.
      Muscle fiber type changes and myosin heavy chain composition were also compared.
      All major fiber types (I, IIA, IIB) became significantly larger after training,
      and a transition of type IIB fibers to IIA occurred with training. The area
      occupied by each fiber type correlated with myosin heavy chain percentage, and
      both of these changed similarly with strength training. The cytoplasm-to
      myonucleus ratio increased, but not significantly (p = .07), with muscle fiber
      hypertrophy. Number of myonuclei per fiber and myonuclei per unit length of
      muscle fiber increased, but not significantly. Cross-sectional areas of the
      muscle fibers in untrained elderly men were much smaller than in untrained young
      men (when compared with our earlier studies). Training increased the sizes of the
      elderly muscle fibers to that of the untrained young men. This hypertrophy of
      muscle fibers by 30% with training resulted in no change in the cytoplasm-to
      myonucleus ratio. This suggests that the myonuclear population continues to adapt
      to growth stimuli in the elderly muscles.

PMID- 10898249
TI  - In vitro oxidation of low-density lipoprotein in two species of nonhuman primates
      subjected to caloric restriction.
AB  - Caloric restriction (CR), which increases longevity and retards age-associated
      diseases in laboratory rodents, is being evaluated in nonhuman primate trials. CR
      reduces oxidative stress in rodents and appears to improve risk factors for
      cardiovascular disease in nonhuman primates. We tested the hypothesis that low
      density lipoprotein (LDL) oxidizability is reduced in two monkey species (rhesus
      and cynomolgus) subjected to chronic CR. In both species, no significant
      differences occurred between CR and control animals on total, LDL, or high
      density lipoprotein (HDL) cholesterol. In rhesus monkeys, triglycerides were
      higher in controls than CR (139 +/- 23 vs 66 +/- 8 mg/dl,p < .01, respectively).
      LDL from CR rhesus monkeys was reduced in triglyceride content and molecular
      weight compared to controls, whereas LDL composition in cynomolgus monkeys was
      similar in CR and control animals. In keeping with minor deviations in lipids,
      antioxidants, and LDL composition, no consistent differences in in vitro LDL
      oxidizability were apparent between CR and controls in either species.

PMID- 10898250
TI  - Water, water everywhere and not a drop to drink.

PMID- 10898251
TI  - Do elderly persons need to be encouraged to drink more fluids?
AB  - BACKGROUND: A recently published and widely quoted modified food guide pyramid
      encourages persons over the age of 70 years to ingest eight glasses (2 liters) of
      fluids per day. We challenge the need for this much fluid intake and even
      question whether it may do more harm than good. METHODS: Equal numbers of
      Hispanic and non-Hispanic white men and women were selected randomly from the
      Health Care Financing Administration (Medicare) rolls and recruited for a home
      interview followed by a 4-hour interview/examination in a senior health clinic.
      Questionnaires and examinations were used to determine usual daily self-reported
      intake of fluids, lying and standing blood pressures, history of falls over the
      past year, and the presence of chronic constipation and chronic fatigue or
      tiredness. Serum samples were obtained for determination of sodium, urea nitrogen
      (SUN) and creatinine concentrations, and calculation of SUN/creatinine ratios.
      RESULTS: Interviews/examinations were conducted on 883 volunteers (mean age of
      74.1 years). Most participants (71%) estimated that their usual fluid intake was
      equal to or exceeded six glasses per day. Evidence of hypernatremia (serum sodium
      concentration > 146 mEq/l) was not observed in the 227 individuals ingesting less
      than this. Hyponatremia also was rare in this population. Fluid intake showed no
      significant associations with lying and standing blood pressures, a history of
      falling, or the frequency of chronic constipation or fatigue/tiredness.
      CONCLUSION: Until we have more evidence-based documentation that fluid intake of
      eight glasses (2 liters) per day improves some aspect of an elderly person's
      health, encouraging a fluid intake above a level that is comfortable for the
      individual seems to serve little useful purpose.

PMID- 10898252
TI  - Oral health problems and significant weight loss among community-dwelling older
      adults.
AB  - BACKGROUND: Studies of hospitalized and institutionalized older adults suggest a
      relationship between poor oral health and subsequent weight loss. Given the
      association between weight loss and subsequent mortality and morbidity, we
      evaluated how oral health problems contributed to significant weight loss over a
      1-year period among a representative sample of community-dwelling older adults.
      METHODS: The study population consisted of 563 adults aged 70 years and older
      living at home in rural and urban areas in six New England states. Baseline data
      included information regarding health status, functional status, physical
      activity, disease diagnoses, lifestyle behaviors, and cognitive and affective
      status. Dentists performed oral health assessments. One year later, participants
      were called and asked questions regarding their health and dietary practices and
      their current weight. RESULTS: Over the 1-year period of follow-up, approximately
      one third of the sample had lost 4% or more of their previous total body weight;
      6% of men and 11% of women lost 10% or more of their previous body weight. Of the
      subjects, 37% were edentulous; most of these individuals wore full dentures. With
      gender, income, advanced age, and baseline weight controlled for, edentulousness
      remained an independent risk factor for significant weight loss (odds ratio 1.63
      for 4% weight loss and 2.03 for 10% weight loss). Individuals with increasing
      numbers of posterior teeth and functional units were at slightly lower risk for
      weight loss; however, these associations did not reach statistical significance.
      CONCLUSIONS: Dentate status is an important risk factor for clinically
      significant weight loss among community-dwelling older adults.

PMID- 10898253
TI  - What can we do to improve physical function in older persons with type 2
      diabetes?
AB  - BACKGROUND: Older persons with type 2 diabetes are at higher risk for functional
      impairment than are their age-matched counterparts without-diabetes. We therefore
      sought to identify factors associated with impaired physical function in older
      persons with type 2 diabetes by using a cross-sectional study design. METHODS: We
      studied 1238 persons with type 2 diabetes who were 55 years of age or older and
      enrolled in the Type II Diabetes Patient Outcomes Research Team (PORT) project.
      Subjects were primary care patients at a large staff model health maintenance
      organization who had completed a mailed survey that collected information about
      demographics (age, race, marital status, income, education, gender, and body mass
      index [BMI]), health behaviors (exercise, smoking, and alcohol), care and control
      of diabetes (therapy, self-reported glucose control, home glucose monitoring, and
      disease duration), mood (Center for Epidemiologic Studies--Depression Scale [CES
      D]), comorbidity, and the Short-Form-36 health survey (SF-36). We evaluated the
      bivariate relationships between the PFI- 10, a 10-item measure of physical
      function from the SF-36, and candidate independent variables from the domains
      described previously. Variables that were significant at an a level of .10 were
      entered into a multiple linear regression model. RESULTS: There were eight
      independent predictors of impaired physical function (all p < .05, R2 = .40).
      Factors associated with impaired function in order of their relative importance
      were as follows: a higher comorbidity score, older age, obesity, lack of regular
      exercise, CES-D score higher than 20, taking insulin, lower formal education, and
      abstinence from alcohol. CONCLUSIONS: Increased comorbidity and older age are
      associated with poorer function, as is the severity of diabetes and less formal
      education. Exercise, lower BMI, and better mood are associated with better
      function. Therefore, promoting regular exercise and weight loss, in addition to
      treating depression, are likely to preserve or even improve the functional status
      of older persons with type 2 diabetes. Moderate alcohol use may be beneficial as
      well. The extent to which these relationships persist in prospective studies or
      clinical trials remains to be evaluated.

PMID- 10898255
TI  - Factors associated with antiepileptic drug use among elderly nursing home
      residents.
AB  - BACKGROUND. Epilepsy, a chronic condition defined as two or more recurrent,
      unprovoked seizures, has the highest incidence at the end of life. Antiepileptic
      drugs (AEDs) are the primary therapeutic mode. Approximately 10%-11% of elderly
      nursing home residents receive one or more AEDs, a higher prevalence than would
      be expected in this age group. In the research literature, there is not a clear
      explanation of variations in AED use in nursing homes. The purpose of this study
      was to examine the prevalence and variations in use of AEDs by resident
      characteristics, AEDs used, drug dosage, and AED combinations in treatment
      regimens. METHODS: This was a retrospective, cross-sectional study of residents
      (N = 21,551) in a convenience sample of nursing homes in 24 states and the
      District of Columbia. The unit of analysis was the individual resident. The study
      period was a single day in 1995. Bivariate and multivariate analyses were used to
      test differences. RESULTS: The prevalence of AED use was 10.5% across all elderly
      residents. In a multivariate analysis, factors associated with AED treatment
      included seizure indication, age group, and geographic region. AED use by age
      group showed declining use as the residents aged, from 65-74 to 75-84 to > or =85
      years. CONCLUSIONS: The inverse relationship between AED use and age group was
      unexpected because the incidence of epilepsy increases with advancing age. This
      finding raises important questions about the future use of these drugs in elderly
      nursing home residents.

PMID- 10898254
TI  - Report of having slowed down: evidence for the validity of a new way to inquire
      about mild disability in elders.
AB  - BACKGROUND: Mild disability in elderly persons may be detected by eliciting
      reports of modified task performance, even in the absence of reported difficulty.
      This study provides evidence for the validity of one type of task modification.
      namely, slowing, as a measure of mild walking disability. METHODS: Community
      dwelling elders (N = 287) were questioned about whether they were walking indoors
      as quickly as they had 1 year before and 10 years before. Construct validity was
      assessed by the degree to which responses to these two questions were logically
      consistent with a general decline in walking speed, and by determining whether
      reported slowing was associated with concurrent reports of difficulty walking and
      with measured gait speed. Predictive validity in subjects without reported
      difficulty walking was gauged by the association of reported slowing with adverse
      walking outcomes at 1-year follow-up. RESULTS: Reports of slowing over 10- and 1
      year periods were almost uniformly consistent with a general decline in speed.
      Reported slowing was significantly associated with reported difficulty walking
      and with slower gait speed. In the subgroup of elders initially reporting no
      difficulty walking, reported slowing significantly predicted incident difficulty
      walking at follow-up, as well as other adverse walking outcomes. For example,
      among elders who reported slowing, 7%, 10%, and 19% developed new difficulty
      walking indoors, new difficulty walking outdoors, or stopped walking for
      pleasure, compared with 0%, 0%, and 3% for those who had not reported slowing (p
      < .05). CONCLUSIONS: This study provides evidence for the construct and
      predictive validity of one type of task modification, namely, slowing in indoor
      walking. This work contributes to the development of new methods for measuring
      mild disability, which may in turn form the basis for clinical interventions
      based on the early identification of functional problems.

PMID- 10898256
TI  - Pain factors associated with physical disability in a sample of community
      dwelling senior citizens.
AB  - BACKGROUND: Little is known about the specific aspects of pain that may
      contribute to the association between pain and disability. This study
      investigated whether the presence of a physical disability is associated with
      specific aspects of musculoskeletal pain. METHODS: Questionnaires sent to a
      sample of community-dwelling seniors included detailed questions about pain; the
      topics covered pain intensity, frequency, duration and location, use of pain
      medication, cause of pain, physical disability, depressive symptoms, chronic
      conditions, and demographic information. RESULTS: Of the 885 respondents, 644
      reported musculoskeletal pain (mean age = 75.85 years, SD = 5.83; 63.2% men vs
      36.8% women). Multiple logistic regression analysis revealed that pain of severe
      or greater intensity was shown to be significantly associated with disability
      (odds ratio [OR] = 4.32, 95% confidence interval [CI] 2.01 and 9.01,
      respectively). Pain experienced all or nearly all of the time (OR = 2.00, 95% CI
      1.07 and 3.72) and taking pain medication (OR = 1.64, 95% CI 1.08 and 2.5 1) were
      also shown to be associated with disability. The number of pain locations
      reported by the respondents was also shown to be significantly associated with
      disability. The OR for the mean number of pain locations (5.8 locations out of a
      possible 45) was calculated to be 2.12 (95% CI 1.43 and 3.16). CONCLUSION: A
      thorough pain evaluation and appropriate management of certain aspects of pain
      may aid in the independent functioning of elderly persons.

PMID- 10898257
TI  - Does private religious activity prolong survival? A six-year follow-up study of
      3,851 older adults.
AB  - BACKGROUND: Previous studies have linked higher religious attendance and longer
      survival. In this study, we examine the relationship between survival and private
      religious activity. METHODS: A probability sample of elderly community-dwelling
      adults in North Carolina was assembled in 1986 and followed for 6 years. Level of
      participation in private religious activities such as prayer, meditation, or
      Bible study was assessed by self-report at baseline, along with a wide variety of
      sociodemographic and health variables. The main outcome was time (days) to death
      or censoring. RESULTS: During a median 6.3-year follow-up period, 1,137 subjects
      (29.5%) died. Those reporting rarely to never participating in private religious
      activity had an increased relative hazard of dying over more frequent
      participants, but this hazard did not remain significant for the sample as a
      whole after adjustment for demographic and health variables. When the sample was
      divided into activity of daily living (ADL) impaired and unimpaired, the effect
      did not remain significant for the ADL impaired group after controlling for
      demographic variables (hazard ratio [RH] 1.11, 95% confidence interval [CI] 0.91
      1.35). However, the increased hazard remained significant for the ADL unimpaired
      group even after controlling for demographic and health variables (RH 1.63, 95%
      CI 1.20-2.21), and this effect persisted despite controlling for numerous
      explanatory variables including health practices, social support, and other
      religious practices (RH 1.47, 95% CI 1.07-2.03). CONCLUSIONS: Older adults who
      participate in private religious activity before the onset of ADL impairment
      appear to have a survival advantage over those who do not.

PMID- 10898258
TI  - Sleep disturbances and their correlates in elderly Japanese American men residing
      in Hawaii.
AB  - BACKGROUND: Elderly people frequently report the presence of chronically
      disturbed sleep. However, most data are derived from predominantly Caucasian
      populations. The current study is an investigation of the prevalence and
      correlates of sleep disturbances in a cohort of elderly Japanese American men
      residing in Hawaii. The importance of this population lies in its representation
      of an ethnic group living in a culture different from their ancestry. METHODS:
      This study is a cross-sectional cohort analysis of data pertaining to sleep
      disturbances and their potential correlates from 3,845 elderly Japanese American
      men residing in Hawaii (mean age. 78 years; range, 71-93 years) who participated
      in the fourth survey of the Honolulu Heart Program (1991-1994), which is the
      baseline exam for the Honolulu-Asia Aging Study. Information collected included
      an extensive survey of medication use, medical history, and assessments of
      physical and mental function, quality of life, and sleep. RESULTS: The prevalence
      of insomnia (DIMS) was 32.6%, a rate similar to that reported in predominantly
      Caucasian populations. Depression, benzodiazepine use, and several chronic health
      problems were the most important factors associated with DIMS. In contrast,
      excessive daytime sleepiness (EDS) had a prevalence of 8.9%, a rate lower than
      that found in elderly Caucasian populations but close to that reported among
      native Japanese. Important factors related to EDS were symptoms of nocturnal
      respiratory disturbance, depression, perception of adverse quality of life,
      Parkinson's disease, and digitalis use. CONCLUSIONS: Elderly Japanese men are
      less likely than elderly Caucasian men to report excessive daytime sleepiness.
      However, their insomnia rates are similar.

PMID- 10898259
TI  - Medication administration hassles reported by family caregivers of dependent
      elderly persons.
AB  - BACKGROUND: Even under the new long-term care mantra for increased home- and
      community-based care options, attention to and an understanding of the ways that
      family caregivers are managing complex care for dependent elderly persons, for
      example, with medication administration, have been slow to materialize. METHODS:
      Twenty-three family caregivers completed semistructured, face-to-face interviews
      to capture the shared and idiosyncratic experiences of individuals responsible
      for all aspects of medication administration regimens for elderly, dependent
      family members. Data analysis consisted of content analysis of the verbatim
      interview transcripts. This article reports an emerging typology of caregiver
      medication administration hassles derived from the interviews. RESULTS: Based on
      122 separate accounts, three categories of medication administration hassles were
      identified. The categories (with the percentage of all accounts represented by
      the category) include (i) scheduling logistics (29.5%), (ii) administration
      procedures (31.9%), and (iii) safety issues (38.6%). CONCLUSIONS: Primary care
      providers must continually reevaluate and simplify medication regimens for
      dependent elderly persons in the care of family members, and the family
      caregivers must be given adequate training and access to ongoing information
      support systems to help them perform safe and effective medication administration
      responsibilities.

PMID- 10898260
TI  - Physical activity, disability, and the risk of hospitalization for breast cancer
      among older women.
AB  - BACKGROUND: A recent investigation of physical activity, disability, and the risk
      of breast cancer among older women in the Iowa 65 + Rural Health Study reported a
      decreased risk of breast cancer among women with any disability compared with
      physically capable but inactive women (relative risk [RR] = 0.4. 95% confidence
      interval [CI] 0.2-0.9). Because of the intriguing nature of that association,
      those investigators urged replication before drawing any conclusions. METHODS: We
      replicated the Iowa approach using the Longitudinal Study on Aging (LSOA). a
      nationally representative, prospective cohort study. The 3131 community-dwelling
      women for whom we had complete data for these analyses ranged in age from 70 to
      98 years old at baseline in 1984. Using ICD9-CM 174 codes, linked Medicare
      hospital claims identified 77 women with hospitalizations for breast cancer
      between 1984 and 1991. Multivariable proportional hazards regression was used to
      model the risk for this event among disabled, inactive, moderately active, and
      highly active women. RESULTS: No significant association between disability in
      older women and the risk of hospitalization for breast cancer relative to
      inactive older women was detected (adjusted hazard ratio [AHR]-0.78, 95% CI 0.41
      1.5). Highly active older women had a significantly reduced risk of
      hospitalization for breast cancer (AHR-0.42, 95% CI 0.194).95). CONCLUSION: The
      intriguing finding from the Iowa 65+ Rural Health Study that disabled older
      women's risk for breast cancer was reduced could not be replicated in the LSOA,
      although power was limited. Highly active older women, however, had a
      significantly lower risk for breast cancer in both studies.

PMID- 10898261
TI  - Two review articles (Arokoski et al., Tyyni & Karlsson) dealing with articular
      cartilage in this and the coming issue treat two different aspects of joint
      cartilage and disease.

PMID- 10898262
TI  - Normal and pathological adaptations of articular cartilage to joint loading.
AB  - Joints are functional units that transmit mechanical loads between contacting
      bones during normal daily or specialized activities, e.g., sports. All components
      of the joint, i.e. articular cartilage, bone, muscles, ligaments/tendons and
      nerves, participate in load transmission. Failure in any of these components can
      cause joint malfunction, which, in turn, may lead to accumulation of damage in
      other joint components. Mechanical forces have great influence on the synthesis
      and rate of turnover of articular cartilage molecules, such as proteoglycans
      (PGs). Regular cyclic loading of the joint enhances PG synthesis and makes
      cartilage stiff. On the other hand, loading appears to have less evident effects
      on the articular cartilage collagen fibril network. Continuous compression of the
      cartilage diminishes PG synthesis and causes damage of the tissue through
      necrosis. The prevailing view is that osteoarthrosis (OA) starts from the
      cartilage surface through PG depletion and fibrillation of the superficial
      collagen network. It has also been suggested that the initial structural changes
      take place in the subchondral bone, especially when the joint is exposed to an
      impact type of loading. This in turn would create an altered stress pattern on
      joint surfaces, which leads to structural damage and mechanical failure of
      articular cartilage. The importance of the neuromuscular system to the initiation
      and progression of OA is still poorly understood. Many surgical extra- and intra
      articular procedures have been used for the treatment of OA. Although some of the
      new methods, such as autologous chondrocyte transplantation and mosaicplasty,
      have given good clinical results, it is reasonable to emphasize that the methods
      still are experimental and more controlled studies are needed.

PMID- 10898263
TI  - Effect of stride length on symptoms of exercise-induced muscle damage during a
      repeated bout of downhill running.
AB  - The purpose of this study was to assess the effects of changes in stride length
      on the symptoms of exercise-induced muscle damage (EIMD) during a repeated bout
      of downhill running in a group of 18 men and women. Muscle tenderness, plasma
      creatine kinase activity (CK) and maximal voluntary isometric force were measured
      before and after two downhill runs, with each run separated by 5 weeks. The first
      downhill run was at the preferred stride frequency (PSF). Participants were then
      randomly allocated to one of three sex-balanced groups with equal numbers of men
      and women: overstride (-8% PSF), understride (+8% PSF) and normal stride
      frequency for the second downhill run. Stride length had no effect (P>0.05) on
      muscle tenderness, CK or isometric peak force. Increases in muscle tenderness
      (P<0.001) and CK were lower (P<0.05) following the second downhill run, although
      there was no difference in the pattern and extent of the strength decrement
      between the two runs. There were also no differences (P>0.05) in muscle
      tenderness, CK or the relative strength loss between the men and the women.
      Results suggest that the symptoms of EIMD are unaffected by gender and small
      alterations to the normal stride pattern during constant velocity downhill
      running. The observation that muscle tenderness and CK were reduced following a
      repeated bout of similar eccentric exercise is consistent with the phenomenon
      known as the 'repeated bout effect' of muscle damage.

PMID- 10898264
TI  - Specific protein alteration in the soleus following immobilization-atrophy.
AB  - To investigate the effect of immobilization in a shortened position on protein
      alteration in the mouse soleus, total protein from immobilized and control muscle
      were analyzed by SDS-PAGE and two-dimensional polyacrylamide gel electrophoresis.
      Five-week-old male ddY mice (n=22) were used throughout this study. A 67.3 kDa
      protein was significantly increased by 1.7-fold in the immobilized muscles in SDS
      PAGE compared to control muscle (P<0.001). This protein had the same mobility as
      serum albumin. The isoelectric point of the 67.3 kDa protein was pH 6.3, similar
      to serum albumin (range from pH 6.0 to 6.3). Specific antibody to the 67.3 kDa
      protein reacted with serum albumin by Western blot analysis. This protein was
      localized in the interstitial space in the control muscle and accumulated in
      pathologic areas in the immobilized muscle. It was presumed that this protein was
      a serum albumin-like protein.

PMID- 10898265
TI  - The effect of heart rate controlled low resistance circuit weight training and
      endurance training on maximal aerobic power in sedentary adults.
AB  - The effects of a 12-week low resistance circuit weight training (CWT) on
      cardiovascular and muscular fitness were studied in 90 healthy sedentary adults.
      The subjects were randomized into three equally fit groups: CWT, Endurance (END)
      and Control (CON) according to their maximal aerobic power (VO2max). Both
      training groups exercised for 12 weeks, 3 days a week in sessions of 40 min, with
      a heart rate (HR) level of 70-80% HRmax. The CWT group trained with air
      resistance machines. Heart rate was controlled by setting the speed of movement.
      The END group walked, jogged, cross-country skied or cycled. The net differences
      (between pre- and posttraining changes) between the CWT and CON groups was
      statistically significant for VO2max (2.45 ml x min(-1) x kg(-1), 95% CI 1.1;
      3.8), for abdominal muscles (3.7 reps, CI 0.3; 7.1), for push-ups (1.1 reps, CI
      0.2; 2.1), and for kneeling (2.25 reps, CI 0.01; 4.5). The net difference
      (between pre- and posttraining changes) in the END and CON groups was
      statistically significant for VO2max (2.75 ml(-1) x min(-1) x kg(-1), 95% CI 0.9;
      4.6), and kneeling (3.0 reps, CI 0.7; 5.3). Low resistance CWT with moderately
      hard HR level has effects comparable to an equal amount of endurance training on
      the cardiovascular fitness of sedentary adults. The CWT model was benefical also
      on muscular fitness. Based on the results, this type of exercise can be
      recommended for beginners because of its multilevel effects.

PMID- 10898266
TI  - Patellar tendinopathy in junior basketball players: a controlled clinical and
      ultrasonographic study of 268 patellar tendons in players aged 14-18 years.
AB  - Anterior knee pain is a common presenting complaint amongst adolescent athletes.
      We hypothesised that patellar tendinopathy may occur at a younger age than is
      generally recognised. Thus, we studied the patellar tendons in 134 elite 14- to
      18-year-old female (n=64) and male (n=70) basketball players and 29 control
      swimmers (17 female, 12 male) clinically and with ultrasonography. We found that
      of 268 tendons, 19 (7%) had current patellar tendinopathy on clinical grounds
      (11% in males, 2% in females). Twenty-six percent of the basketball players'
      patellar tendons contained an ultrasonographic hypoechoic region.
      Ultrasonographic abnormality was more prevalent in the oldest tertile of players
      (17-18 years) than the youngest tertile (14-15.9 years). Of tendons categorised
      clinically as 'Never patellar tendinopathy', 22% had an ultrasonographic
      hypoechoic region nevertheless. This study indicates that patellar tendinopathy
      can occur in 14- to 18-year-old basketball players. Ultrasonographic tendon
      abnormality is 3 times as common as clinical symptoms.

PMID- 10898267
TI  - Anterior knee pain 7 years after an anterior cruciate ligament reconstruction
      with a bone-patellar tendon-bone autograft.
AB  - In order to evaluate the occurrence and predicting factors of anterior knee pain
      in patients after an anterior cruciate ligament reconstruction with a bone
      patellar tendon-bone autograft, a functional, clinical and radiographic
      evaluation was performed on 91 patients on average 7 years after the surgery.
      Also, the isokinetic muscle torque was measured. At 7 years, anterior knee pain,
      as classified by the International Knee Documentation Committee (IKDC), was
      absent in 40 patients, mild in 47 patients, and moderate in 4 patients. None was
      classified as suffering from severe anterior knee pain. In the logistic
      regression analysis of predicting factors (forward-stepping), knee extension
      torque deficit of the operated limb was the only factor that showed significant
      association with anterior knee pain. The other objective measurements of the knee
      (flexion torque deficit, range of motion, stability evaluation, and radiographic
      evaluation of the knee) were not associated with anterior knee pain. Subjectively
      and not surprisingly, the patients without anterior knee pain were more often
      satisfied with the overall outcome than the patients with anterior knee pain.
      Also, the Lysholm and Marshall knee scores and the final outcome in the IKDC
      rating scale were significantly better in patients without than with anterior
      knee pain.

PMID- 10898268
TI  - Waist circumference and VO2max are associated with metabolic and hemostatic risk
      in premenopausal nurses.
AB  - In 21 nurses (34.4+/-3.9 yr), VO2max physical activity, body composition and
      lifestyle parameters were measured to determine which of these characteristics
      are related to metabolic and hemostatic risk for cardiovascular disease. Physical
      activity was assessed with the 7-day recall interview. VO2max was measured in a
      progressive and continuous treadmill test to volitional fatigue. Fasting insulin,
      total cholesterol, HDL-C, triglycerides, fibrinogen, tPA-act, tPA-ag, and PAI-1
      ag were determined from fasting blood samples. Contrary to our expectation, there
      was no association of physical activity with any of these risk indicators. High
      VO2max was associated with lower levels of insulin and fibrinogen. Regression
      analyses indicated that metabolic and hemostatic risk indicators, as measured in
      healthy premenopausal nurses, were mainly predicted by waist circumference and
      oral contraceptive use.

PMID- 10898269
TI  - Physical activity and bone mineral acquisition in peripubertal girls.
AB  - The association of the amount and type of physical activity with bone mineral
      acquisition was studied in 191 peripubertal Caucasian girls aged 9-16 years (66
      gymnasts, 65 runners, and 60 nonathletic controls). Weight, height, stage of
      puberty, the amount of leisure-time physical activity, and years of training were
      recorded, and dietary calcium and vitamin D were assessed by a semi-quantitative
      questionnaire. The bone area, the bone mineral density (BMD), and the bone
      mineral content (BMC) of the femoral neck, lumbar spine and antebrachium were
      measured by dual-energy x-ray absorptiometry. The unadjusted mean values of BMD
      at the femoral neck were 15.2% higher in the pubertal gymnasts than in the
      controls (P<0.001). Compared with the controls, the mean BMC adjusted for bone
      area of the pubertal gymnasts at the femoral neck and lumbar spine was 16.4% and
      10.8% higher, respectively. When comparing the association of the type of
      physical activity among the pubertal athletics by multiple regression analysis,
      height, physical activity, gymnastics, and Tanner stage emerged as significant
      variables and accounted for 54.7% and 63.4% of the total variation in BMD of the
      femoral neck and lumbar spine, respectively. These results indicate that physical
      activity is associated with bone mineral acquisition in peripubertal girls and
      that high-impact weight-bearing exercise seems to be particularly associated with
      the increase of the BMD at the femoral neck.

PMID- 10898270
TI  - Recurrent miscarriage syndrome due to blood coagulation protein/platelet defects:
      prevalence, treatment and outcome results. DRW Metroplex Recurrent Miscarriage
      Syndrome Cooperative Group.
AB  - Although first-time miscarriages are usually caused by chromosomal defects, about
      55% of recurrent miscarriages are caused by procoagulant defects that induce
      thrombosis and infarction of placental vessels. Of recurrent miscarriages, about
      7% are caused by chromosome defects, 15% to hormonal defects, and 10% to 15% to
      anatomical defects. Recurrent miscarriage involves more than 500,000 women in the
      United States each year. During the past 4 years, 179 patients, prescreened for
      chromosomal, hormonal, and anatomical defects, and found to harbor none,
      underwent hemostasis defect evaluation. A total of 160 of these have been
      analyzed. A hemostasis defect was found in 150 of 160 women (n = 94% of screened
      women). The mean age was 33 years; the mean number of miscarriages before
      referral was three. All women with a procoagulant defect (149) were treated with
      preconception ASA at 81 mg/d, and unfractionated porcine heparin at 5000 U every
      12 hours was added immediately postconception; both agents were used to term
      delivery. Only two of 149 patients failed therapy. The defects found were as
      follows: antiphospholipid syndrome, 67%; sticky platelet syndrome, 21%; tissue
      plasminogen activator (TPA) deficiency, 9%; factor V Leiden, 7%; high PAI-1, 6%;
      protein S, 5%; high LP(a), 3%; AT, 2%; protein C, 1%. Thirty-eight patients had
      more than one defect. In the group with antiphospholipid syndrome, 24% only had a
      subgroup antibody (antiphosphatidyl-serine, -inositol, -ethanolamine, -choline, 
      glycerol) or antiphosphatidic acid antibody, in the absence of anticardiolipin
      antibody or lupus anticoagulant. This finding is similar to that recently
      reported in early age ischemic stroke patients (<50 years old). In summary, about
      55% of patients with recurrent miscarriage harbor a procoagulant defect to
      account for placental vascular occlusion. More than 98% will have a normal term
      delivery with preconception aspirin (ASA) and addition of postconception heparin
      to term. Patients should be screened by an obstetrician or by reproductive
      specialists for hormonal and anatomic defects before initiating a procoagulant
      evaluation; if such prescreening is done, the yield of a defect is high and
      appropriate therapy leads to an excellent outcome.

PMID- 10898271
TI  - Secondary prevention of myocardial infarction: beneficial effect of combining
      oral anticoagulant plus aspirin: therapy based on evidence.

PMID- 10898272
TI  - G to A 20210 prothrombin polymorphism and venous thrombosis: simple association
      or causal relationship?

PMID- 10898273
TI  - Effect of sarpogrelate hydrochloride on platelet-derived microparticles and
      various soluble adhesion molecules in diabetes mellitus.
AB  - We measured platelet-derived microparticles, activated platelets, and various
      adhesion molecules in 48 patients with diabetes mellitus. We also performed a
      comparative study of these parameters before and after administration of
      sarpogrelate hydrochloride. The numbers of platelet-derived microparticles and
      activated platelets were increased significantly in diabetic patients, and CD63
      positive platelets were increased in patients with diabetic complications and
      poorly controlled blood glucose. Soluble adhesion molecules and thrombomodulin
      were also increased significantly. After administration of sarpogrelate
      hydrochloride, not only CD62p- and CD63-positive platelets, but also platelet
      derived microparticles were decreased significantly. Soluble adhesion molecules
      and thrombomodulin were also significantly decreased after the treatment. These
      data suggest that (a) in patients with diabetes, antiplatelet therapy with
      sarpogrelate hydrochloride is a useful antithrombin therapy because it suppresses
      the production of intrinsic coagulants by activated platelets; and (b)
      sarpogrelate hydrochloride decreases endothelial cell damage via adhesion
      molecules.

PMID- 10898274
TI  - Coagulation tests and anti-phospholipid antibodies in patients positive for lupus
      anticoagulant.
AB  - We examined activated partial thromboplastin time, kaolin clotting time, mixing
      with normal plasma in kaolin clotting time, dilute Russell's viper venom time,
      dilute Russell's viper venom time at high lipid concentrations, anti-phospholipid
      antibodies, and anti-cardiolipin-beta2-glycoprotein I complex antibody in 135
      patients with prolongation of activated partial thromboplastin time and diagnosed
      86 patients positive for lupus anticoagulant. The sensitivity of activated
      partial thromboplastin time and dilute Russell's viper venom time/dilute
      Russell's viper venom time-high lipid concentrations ratio for lupus
      anticoagulant were markedly high, but the specificity of activated partial
      thromboplastin time for lupus anticoagulant was not markedly high. The
      specificity, but not the sensitivity, of kaolin clotting time-mixing with normal
      plasma in kaolin clotting time was markedly high. In summary, dilute Russell's
      viper venom time to dilute Russell's viper venom time-high lipid concentrations
      ratio gave high sensitivity as well as specificity, being the only assay to
      confirm this. Of the patients positive for lupus anticoagulant, 25% were positive
      for anti-phospholipid antibodies and 17% were positive for anti-cardiolipin-beta2
      glycoprotein I complex antibody. Of the lupus anticoagulant-positive patients
      with thrombosis, 45% were positive for anti-phospholipid antibodies, 35% were
      positive for anti-cardiolipin-beta2-glycoprotein I complex antibody, 60% were
      positive for both anti-phospholipid antibodies and anti-cardiolipin-beta2
      glycoprotein I complex antibody, and only 17% were negative for anti-phospholipid
      antibodies and anti-cardiolipin-beta2-glycoprotein I complex antibody. These
      findings suggest that lupus anticoagulant can be diagnosed by dilute Russell's
      viper venom time/dilute Russell's viper venom time-high lipid concentrations
      ratio, and that thrombosis in lupus anticoagulant-positive may be predictable
      from both anti-phospholipid antibodies and anti-cardiolipin-beta2-glycoprotein I
      complex antibody. Plasma tissue type plasminogen activator level in lupus
      anticoagulant patients was significantly increased, and plasma tissue type
      plasminogen activator and fibrin-D-dimer levels in lupus anticoagulant-positive
      patients with thrombosis were significantly higher than in those without
      thrombosis, suggesting that the diagnosis of thrombosis by hemostatic markers
      might be important in lupus anticoagulant.

PMID- 10898275
TI  - Heparin-induced thrombocytopenia: a critical risk/benefit analysis of patients in
      intensive care treated with R-hirudin.
AB  - Patients in intensive care may be at high risk of in vivo platelet activation
      because comorbid conditions, such as infections, septicemia, shock, disseminated
      intravascular coagulation, and cancer represent procoagulant states.
      Hyperreactivity of platelets with or without a decline of cell count may result
      in thromboembolic complications potentially associated with the phenomenon of
      heparin-induced thrombocytopenia. We analyzed the data of 10 patients highly
      suspected of having heparin-induced thrombocytopenia during their intensive care
      treatment of 29 plus or minus 22 days. In seven patients, thrombocytopenia
      coincided with thromboembolic complications. Six patients had additionally
      undergone fibrinolytic therapy before starting activated partial thromboplastin
      time-adapted alternative anticoagulation with r-hirudin. In three patients, the
      platelet count decreased without a clinical manifestation, of heparin-induced
      thrombocytopenia. R-Hirudin treatment monitored by activated partial
      thromboplastin time and prothrombin time (PT) was effective and safe. The target
      value for activated partial thromboplastin time was a twofold prolongation. In
      four of five patients with deep venous thrombosis, a partial recanalization of
      the lower extremity could be achieved. Three patients with pulmonary embolism
      associated with deep venous thrombosis in two cases and in one additional case
      with an acute myocardial infarction did clinically profit from fibrinolysis with
      recombinant tissue plasminogen activator (rtPA) and r-hirudin treatment. Two
      lethal events probably caused by the underlying multimorbidity could not be
      prevented. No recurrence of thrombosis occurred, and there were no severe
      bleeding complications attributed to r-hirudin treatment. Platelet counts were
      significantly reduced on day 9.4 plus or minus 6.4 of heparin administration in
      all cases (>50% decrease related to the initial values) from 224,000 plus or
      minus 126,000/microL to 96,000 plus or minus 61,000/microL, and increased during
      rhirudin treatment to mean values of 224,000 plus or minus 126,000/microL. The
      heparin-induced platelet activation assay (HIPAA) assay was positive in 8/10
      cases, whereas the PF4 enzyme-linked immunosorbent assay showed a positive result
      in four of eight analyzed cases. In four cases, the assays were concordantly
      positive. The PF4 enzyme-linked immunosorbent assay was not performed in two
      cases.

PMID- 10898276
TI  - Effectiveness of anagrelide in the treatment of symptomatic patients with
      essential thrombocythemia.
AB  - We prospectively evaluated the effect of anagrelide on platelet counts and the
      clinical manifestations of microvascular circulation disturbances in 17 newly
      diagnosed patients with essential thrombocythemia. Ten patients had symptoms
      related to thrombocythemia, eight at the time of starting anagrelide treatment.
      The platelet counts before anagrelide treatment and during maintained remission
      of essential thrombocythemia by anagrelide were 980 (range, 610-2030) and 378
      (range, 212-546) x 10(9)/L, respectively. Spontaneous platelet aggregation was
      found in 6 patients (35%), which disappeared on remission of essential
      thrombocythemia in five cases (P = 0.02). Essential thrombocythemia-related
      microvascular thrombotic and hemorrhagic symptoms disappeared with the
      normalization of platelet count in all cases during maintained remission of
      essential thrombocythemia by long term continuous anagrelide treatment with a
      follow-up period of between 2 and 6 years. However, ET-related symptoms
      reappeared in three patients, coinciding with increased platelet count up to 600
      x 10(9)/L caused by anagrelide dose reduction. We conclude that reduction of
      increased platelet to normal (< 400 x 10(9)/L) in symptomatic patients with
      essential thrombocythemia through use of maintained anagrelide treatment is
      associated with the disappearance of spontaneous platelet aggregation and the
      complete relief of thrombotic and hemorrhagic manifestations.

PMID- 10898277
TI  - Congenital and acquired thrombotic risk factors in women using oral
      contraceptives: clinical aspects.
AB  - We describe the thrombophilic and clinical characteristics of a group of patients
      who suffered venous thrombosis (VT) (n = 36) and ischemic stroke (n = 8) while
      taking oral contraceptives (OC). Our purpose is to ascertain whether there are
      differences between users of second and third generation progestogen and to
      investigate the influence of concurrent congenital and acquired risk factors
      (other than OC) on the onset of the thrombosis. The group of patients included 36
      women with VT and eight with ischemic stroke. The patients' recognized
      predisposing factors were recorded. We also considered age, length of time on OC,
      types of OC, rethrombosis, family history of VT, and the presence of
      thrombophilic genetic defects. In the group of patients with VT, 54% were treated
      with second generation OC (n = 23), and 30% (n = 11) were treated with third
      generation OC. We found no significant statistical differences with respect to
      age and length of time on OC between the two types of OC. The prevalence of
      genetic defects in these patients--factor V (FV) Leiden, prothrombin G20210A
      mutation and protein S deficiency--was 19% (n = 7), 17% (n = 6), and 8% (n = 3)
      respectively. We observed the shortest time lapse between initiating OC and the
      first thrombotic event in carriers of FV Leiden and in patients with combined
      defects, but the differences were not significant. In patients with ischemic
      stroke, 50% were treated with second generation OC and 50% were treated with
      third generation OC. Prothrombin G20210A mutation was detected in two patients.
      In both patients,the stroke occurred earlier than in the rest of the patients,
      but these differences were not statistically significant. With respect to
      preventing thrombotic events in these patients, our data suggest that OC therapy
      should be avoided in patients with a previous history of thrombosis and in
      patients with an evident thrombotic tendency in the family. In patients in whom
      the family history of thrombosis is not very evident, it would be recommended to
      screen for FV Leiden, prothrombin G20210A mutation, and protein S, and to rule
      out OC if the patient does in fact have one of these risk factors. Moreover, if a
      patient develops a thrombotic complication while taking OC, an evaluation to
      search for a thrombophilic defect is warranted, and at the same time, alternative
      methods of contraception should be considered.

PMID- 10898278
TI  - Isoamyl nitrite depolymerized heparin as a universal calibrator for heparins and
      low molecular weight heparins.
AB  - Because the subcutaneous absorption of heparin depends on its molecular weight,
      high performance size exclusion chromatography methods, among others, have been
      developed for its determination. Because heparin consists of polymer chains of
      varying lengths, a large number of calibrators, 19 in our work, are required for
      these molecular weight analyses. Because the preparation of that many calibrants
      is both time-consuming and expensive, other methods requiring fewer calibrants
      are being sought. In pursuit of these aims, a heparinase-degraded heparin has
      been accepted as the first international reference preparation low molecular
      weight heparin for molecular weight calibration. We have previously proposed
      another calibrant, the Heparin Mass Calibrator. In this article, we introduce
      another calibrant, called the Heparin Molecular Mass Calibrant. It offers the
      advantage of a much wider availability because it is a commercial product. In
      addition to having a superior refractive index chromatography run profile, when
      used in combination with two Narrow Range Calibrators with molecular weights of
      34.4 and 18.4 kDa, this new calibrant covers both the higher and the lower
      molecular weight ranges. Besides, ultraviolet detection is not needed for
      molecular weight calculations. Therefore, it is proposed that its feasibility as
      a universal reference calibrator for both heparins and low molecular weight
      heparins be considered.

PMID- 10898279
TI  - Severity of illness, outcomes, and resource use in elderly cancer patients with
      deep venous thrombosis.
AB  - Low-molecular-weight heparins provide new options for outpatient management of
      deep venous thrombosis. Because elderly patients with cancer are at increased
      risk of developing deep venous thrombosis, outpatient therapy for treatment of
      deep venous thrombosis may be important in this population. We compared the
      severity of illness, outcomes, and cost of deep venous thrombosis in elderly
      patients with cancer to those seen in younger patients with cancer. We examined
      all 766 episodes of deep venous thrombosis treated at the University of Texas
      M.D. Anderson Cancer Center between January 1, 1994 and December 31, 1996.
      Severity of illness level and predicted risks of mortality and readmission were
      obtained from a commercially available disease staging system (Inforum System).
      Observed outcomes and cost were based on data collected from the 766 episodes of
      deep venous thrombosis at our institution. One hundred nineteen (16%) episodes of
      deep venous thrombosis occurred in patients 70 years of age or older. The
      severity of illness scale (1-5, least-most severe) were identical (3.7) in the 3
      groups studied (< 70 years, 70-79, years and > or = 80 years). The predicted risk
      of death during hospitalization (6%, 9%, 8%, respectively, by group, P = 0.12)
      and readmission in 30 days (5%, 4%, 3%, respectively, P = 0.04) were similar
      among the groups. The observed death rates during hospitalization were 5%, 6%,
      and 6%, respectively (P = 0.91), and the rates of hospitalization for deep venous
      thrombosis recurrence were 22%, 16%, and 28%, respectively (P = 0.27). The
      similarities in outcomes and resource use between elderly and younger patients
      suggest that elderly patients with cancer are not at greater risk of serious
      clinical outcomes or a prolonged clinical course. There is significant potential
      for outpatient management of these patients.

PMID- 10898281
TI  - Rapid genetic diagnosis in neonatal pulmonary artery thrombosis caused by
      homozygous antithrombin Budapest 3.
AB  - We report a case of spontaneous left pulmonary artery thrombosis in a 3-day-old
      male neonate. The presentation of heparin resistance and thrombosis raised the
      possibility of a type II heparin binding site antithrombin deficiency. A
      continuous infusion of antithrombin concentrate was used successfully, following
      failure of plasma, to correct the heparin resistance. Rapid genetic analysis
      allowed sequencing of the antithrombin gene within 5 working days. This showed
      the infant to be homozygous for the substitution of C to T at nucleotide 2759.
      This base change causes mutation of the native leucine at codon 99 to a
      phenylalanine. This antithrombin variant has been previously reported
      (antithrombin Budapest 3) and results in reduced binding of heparin to
      antithrombin. Such a molecular diagnostic approach is feasible and warranted in
      such cases of neonatal thrombosis because of the diagnostic difficulties
      encountered.

PMID- 10898280
TI  - Portal vein thrombosis associated to prothrombin G20210A mutation and protein C
      deficiency.
AB  - We describe a patient with left branch portal vein thrombosis involving two
      thrombophilic alterations, the prothrombin G20210A mutation and protein C
      deficiency. In spite of not being under anticoagulant treatment, the thrombus in
      the portal vein underwent complete and spontaneous lysis. No other risk factors
      were detected and no family history related to thrombosis was found.

PMID- 10898282
TI  - Granulocyte rheology before and after chemotactic activation in deep venous
      thrombosis.

PMID- 10898283
TI  - Changes in epididymal protein anti-agglutinin on ejaculated boar spermatozoa
      during capacitation in vitro.
AB  - This study is a detailed investigation of changes in epididymal protein anti
      agglutinin on ejaculated boar spermatozoa during an incubation designed to
      promote capacitation in vitro. Ejaculated spermatozoa were collected from six
      mature boars, washed, and incubated to promote capacitation. Sperm samples were
      subjected to Western blotting-densitometric analyses, flow cytometry after
      immunostaining and immunocytochemical observation by indirect immunofluorescence.
      An antiserum to anti-agglutinin was raised in a rabbit by subcutaneous injection
      of a purified antigen, as described previously (Harayama et al. 1999). Western
      blotting-densitometric analyses revealed an approximate halving of the amount of
      sperm-bound anti-agglutinin during the first 45-min incubation, followed by a
      gradual decrease thereafter. Comparison between immunostained sperm samples by
      flow cytometry before and after incubation confirmed this decrease in sperm-bound
      anti-agglutinin during the incubation. Microscopic characterization established
      that this decrease occurred mainly on the acrosome. Supplementation with seminal
      plasma (5% or 10%, v/v) attenuated the decrease. These findings are consistent
      with the conclusion that a large portion of the anti-agglutinin bound to sperm
      acrosomes is released at an early stage of the capacitation process in vitro.

PMID- 10898284
TI  - Effects of hyperthermia on uterine blood flow and shunting through uterine
      arteriovenous anastomoses in the late-pregnant ewe.
AB  - The effect of maternal hyperthermia on uterine blood flow (UBF) through the two
      main uterine arteries and on the proportion of UBF shunted through uterine
      arteriovenous anastomoses (AVAs) was investigated. Eight late-pregnant ewes were
      exposed to normothermic (22-23 degrees C) or hyperthermic (approximately 39
      degrees C) ambient conditions for 8 h. UBF was measured in the left and right
      uterine arteries using flow probes and microspheres were injected into the
      uterine artery before, during and after the experimental period. The distribution
      of microspheres between the uterus and lungs was determined to calculate changes
      in capillary and AVA blood flows. Hyperthermia produced a significant (P<0.05)
      increase in maternal core temperature (+1.5 degrees C), increase in maternal
      blood pH (+0.21; P<0.05) and decrease in maternal pCO2 (-16.2 mmHg; P<0.05).
      Blood flow to the uterine horn ipsilateral to the corpus luteum (CL) remained
      unchanged during hyperthermia, whereas total UBF and blood flow to the
      contralateral uterine horn were significantly decreased (P<0.05), by 23.1% and
      20.8%, respectively, of pre-heat control values. The proportion of UBF shunted
      through uterine AVAs during hyperthermia was not significantly different from
      values observed in normothermic ewes (21.9 +/- 0.7%). Mild to moderate
      hyperthermia in late-pregnant sheep induces respiratory alkalosis and decreases
      total blood flow to the uterus, brought about by a decrease in blood flow to the
      uterine horn contralateral, but not ipsilateral to the CL. Heat treatment does
      not alter the proportion of UBF traversing uterine AVAs.

PMID- 10898285
TI  - Maternal caffeine consumption during pregnancy does not affect preimplantation
      development but delays early postimplantation growth in rat embryos.
AB  - Models for studying prenatal drug-induced intrauterine growth retardation (IUGR)
      have, without exception, measured growth-related factors in the postimplantation
      embryo, fetus or neonate. Therefore, it is not known whether effects of drug
      exposure on growth and metabolism begin early in the preimplantation embryo, or
      whether IUGR is exclusively a postimplantation phenomenon. The present study
      investigates whether caffeine, a drug known to induce a dose-dependent fetal
      IUGR, affects embryo development before and/or after implantation or is
      exclusively a fetal phenomenon. Preimplantation embryo assessment (with treatment
      from Days 2 to 4 of pregnancy) included glucose utilization, cell number
      evaluation and stage of development (morula to hatched blastocyst); whereas,
      postimplantation embryo assessment (treatment from Days 2 to 10, 10.5 or 11 of
      pregnancy) included somite number evaluation and extent of neural tube closure,
      as seen using scanning electron microscopy. Comparing control preimplantation
      embryos with those exposed to 30 and 60 mg kg(-1) caffeine did not reveal any
      effects of caffeine exposure, as assessed on Day 5 of gestation. However,
      postimplantation embryo development assessed on Day 12 of gestation revealed that
      caffeine exposure of 15 and 30 mg kg(-1) significantly reduced, at both dosage
      levels, somite number and the extent of neural tube closure. In addition,
      comparisons of control and experimental groups revealed that in the high-dose
      caffeine group the forebrain cavity was significantly enlarged and bounded by a
      reduced, irregularly aligned neuroepithelium. The findings suggest that IUGR is a
      phenomenon first identifiable during late postimplantation embryogenesis and
      continues in fetal life.

PMID- 10898286
TI  - Antigen-specific systemic and reproductive tract antibodies in foxes immunized
      with Salmonella typhimurium expressing bacterial and sperm proteins.
AB  - Attenuated Salmonella typhimurium strains are potential 'safe' delivery vectors
      of an oral immunocontraceptive vaccine for the European red fox (Vulpes vulpes).
      In the present study, model bacterial (Escherichia coli heat-labile enterotoxin B
      subunit, LTB) and fox sperm (fSP10) antigens were expressed in S. typhimurium
      SL3261 (delta aroA) under the control of the trc promoter. Adult female foxes
      were given three oral immunizations with SL3261 containing either LTB
      (SL3261/pLTB), fSP10 (SL3261/pFSP10) or a control plasmid (pKK233-2 or pTrc99A).
      All foxes raised serum (IgG) and vaginal (IgG and IgA) antibodies against S.
      typhimurium lipopolysaccharide (LPS). Each fox that received SL3261/pLTB raised
      high titre LTB-specific serum and vaginal IgG antibodies. However, only one of
      four foxes immunized with SL3261/pFSP10 raised an anti-fSP10 immune response, in
      the form of low titre serum and vaginal IgG antibodies. No vaginal IgA antibodies
      were raised against either LTB or fSP10 in these experiments. The immune
      responses against recombinant LTB and fSP10 resulted chiefly from the initial
      dose of antigen in the inocula and were minimally influenced by continued in vivo
      antigen expression. This study demonstrates for the first time in the female red
      fox that oral Salmonella can elicit specific systemic and reproductive tract
      antibodies against heterologous, recombinant proteins.

PMID- 10898287
TI  - Reduction in wool follicles prior to birth in Merino sheep.
AB  - This study was undertaken to identify whether all secondary follicles that are
      initiated are present at birth in the Merino fetus, and if not, when does net
      initiation of secondary follicles cease. Skin was sampled from fetal lambs at 36,
      26 and 16 days before the estimated date of parturition and from lambs at birth
      and 2, 4, 6, 8 and 13 weeks after birth. The ratio of secondary to primary
      follicles (S/P) reached a maximum 16 days before birth and was significantly
      lower at birth (P<0.002) and at all postnatal ages (P<0.05). There was no
      difference between S/P at birth and S/P at later ages. Postnatal primary follicle
      density, secondary follicle density and the percentage of fibre-producing
      follicles followed similar patterns to those reported by others. This is the
      first conclusive demonstration that secondary follicle initiation is completed
      several weeks prior to birth and that there are less secondary follicles at birth
      than at 134 days of gestation.

PMID- 10898288
TI  - Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases, induces exit from
      metaphase I arrest in growing pig oocytes.
AB  - Calcium plays an important role in the regulation of meiotic maturation in
      mammalian oocytes. In the present study, mycotoxin cyclopiazonic acid (CPA), an
      inhibitor of calcium-dependent ATPases, was used to mobilize intracellular
      calcium deposits in growing pig oocytes, which had not attained full meiotic
      competence and in which maturation is thus spontaneously blocked at the metaphase
      I stage. CPA treatment significantly increased the ratio of growing oocytes that
      are able to overcome the spontaneously occurring metaphase I block to complete
      their maturation at the metaphase II stage. CPA treatment of a least 2 hours'
      duration is necessary to overcome the metaphase I block in growing oocytes. A
      similar effect upon release from the spontaneous meiotic block at the metaphase I
      stage was observed after treatment of growing pig oocytes with thapsigargin,
      another inhibitor of endogenous calcium-dependent ATPases. Numerous calcium
      deposits in vacuoles, the mitochondria and on the surface of yolk granules in
      growing pig oocytes were observed. CPA treatment is able to mobilize calcium from
      the mitochondria, but deposits in vacuoles and deposits on the surface of yolk
      granules seem to remain intact after CPA treatment. A microinjection of heparin,
      which is known to bind with the inositol trisphosphate receptors, significantly
      decreased the ratio of CPA-treated growing oocytes overcoming the block at the
      metaphase I stage. This indicates that CPA might mobilize calcium in growing pig
      oocytes through inositol trisphosphate receptors. On the other hand, a
      microinjection of procaine or a microinjection of ruthenium red, both inhibitors
      of ryanodine receptors, did not prevent the overcoming of the metaphase I block,
      induced by CPA treatment. The calcium channel blocker, verapamil, significantly
      reduces the proportion of CPA-treated growing oocytes that overcome the metaphase
      I block. This indicates that the influx of calcium from extracellular sources is
      necessary to overcome the metaphase I block. The calmodulin inhibitors ophiobolin
      A and W7 also reduce the proportion of CPA-treated growing oocytes overcoming the
      metaphase I block.

PMID- 10898289
TI  - Timing and regulatory aspects of oocyte maturation in vitro in the tammar wallaby
      (Macropus eugenii).
AB  - Oocytes from a marsupial, the tammar wallaby (Macropus eugenii), resemble those
      of eutherian mammals in their ability to resume meiosis in vitro when cultured
      under suitable conditions. Culture for 42-48 h in Eagle's minimum essential
      medium (EMEM) supplemented with 10% fetal calf serum, and 10 microg mL(-1)
      porcine luteinizing hormone (pLH) was required in order for oocytes, collected
      from the large antral follicles (> 2 mm diameter) of tammar wallabies (primed
      with 6 mg of porcine follicle stimulating hormone twice daily for four days), to
      proceed to metaphase II (MII) of meiosis. Under these conditions, chromatin
      condensation was observed within 4-8 h of culture in 61% of oocytes; metaphase I
      (MI) chromosomes were observed from 18-30 h of culture (66%); and most oocytes
      (76%) progressed to MII by 42 h in vitro. The addition of cycloheximide, a
      protein synthesis inhibitor, at concentrations of 1-100 microg mL(-1), prevented
      maturation of tammar wallaby oocytes in vitro. This effect was reversible, as
      oocytes washed free of cycloheximide after 4 h of incubation were able to
      progress to MII. The addition of cycloheximide to wallaby oocytes at MI of
      meiosis prevented normal progression to MII suggesting that proteins critical for
      nuclear maturation are synthesized throughout the maturation process. Genistein,
      a protein kinase inhibitor decreased maturation of wallaby oocytes in a dose
      dependent manner. However, the concentration required to significantly inhibit
      maturation of wallaby oocytes (60 microg mL(-1)) was greater than that required
      for eutherian species. Most wallaby oocytes were able to undergo germinal vesicle
      breakdown (GVBD) in the presence of high concentrations of genistein but produced
      abnormal chromatin configurations and were unable to progress to MII. Future
      studies will examine whether cytoplasmic changes occur in marsupial oocytes in
      vitro and their temporal relationship to nuclear maturation.

PMID- 10898290
TI  - Expression of intercellular adhesion molecule-1 (ICAM-1) in choriodecidua with
      labour and delivery at term and preterm.
AB  - To evaluate the association between intercellular adhesion molecule-1 (ICAM-1) in
      the choriodecidua and preterm labour and delivery, ICAM-1 mRNA abundance was
      assessed by northern analysis, and protein levels by ELISA, in samples of this
      tissue after term and preterm delivery. The median ICAM-1 mRNA expression
      following preterm delivery (PTD) was 4.8 and 3.8 times (P<0.05), respectively,
      those following elective Caesarean section prior to labour at term (CST) and
      following vaginal delivery after spontaneous labour at term (SLT). The
      concentration of ICAM-1 protein in the PTD samples was 2.2 and 3.0 times (P<0.05)
      those in CST and SLT samples, respectively. The differences between the term
      groups were not significant. The results were substantially the same when a
      preterm spontaneous labour (PTL) subgroup, exclusive of deliveries complicated by
      pre-eclampsia or intrauterine growth restriction, was compared with the term
      groups. Choriodecidual ICAM-1 mRNA expression, but not ICAM-1 protein
      concentration, significantly correlated to the degree of leukocyte infiltration
      of the PTD gestational membranes. Neither correlated significantly to clinical
      indications of intrauterine or neonatal infection. These findings indicate that
      ICAM-1 is expressed by the human choriodecidua and that this expression is
      elevated with preterm labour and delivery, particularly with increased leukocyte
      infiltration.

PMID- 10898291
TI  - The ultrastructure and metabolism of ejaculated tammar wallaby sperm are impaired
      by swim-up procedures when compared with sperm from the cauda epididymidis.
AB  - The metabolism, rate of intracellular accumulation of sugars, motility and
      ultrastructure of ejaculated tammar sperm were impaired by swim-up into
      artificial media, particularly when the cells were subsequently exposed to N
      acetyl-D-glucosamine (NAG). The inclusion of hyaluronate, serum albumin, catalase
      or Desferal in swim-up media helped prevent deterioration of sperm motility, but
      failed to prevent detrimental NAG-induced metabolic and ultrastructural changes.
      However, the sperm were unavoidably diluted during swim-up into artificial media
      and their behavioural properties were modified by dilution. Thus, sperm collected
      from the cauda epididymidis were immotile and their rate of oxygen uptake was low
      in undiluted caudal epididymal semen (CES). Nevertheless, these sperm were
      viable, and vigorous motility was induced by 5- to 50-fold dilution in Krebs
      Ringer phosphate (KRP). Sperm respiration also dramatically increased with
      moderate dilution (5- or 15-fold) in KRP, but decreased again at higher rates (50
      fold). This suggested that motility and the metabolic properties of tammar sperm
      are modified both by dilution and on leaving the suppressing conditions of the
      epididymis. Diluted tammar epididymal sperm also displayed a Pasteur effect, but
      rapidly lost capacity for motility in an oxygen-depleted atmosphere. It was
      concluded that swim-up procedures compromise ejaculated tammar sperm by promoting
      dilution-induced changes. This may alter the permeability of the membrane with
      loss of the enzymes that process the ammonia generated during the metabolism of
      NAG in seminal plasma. Subsequent exposure to NAG further promotes
      ultrastructural damage culminating in loss of viability.

PMID- 10898292
TI  - Origin and ploidy of multipronuclear zygotes.
AB  - Recently, several authors have proposed strategies for correction of triploidy
      based on the removal of the extra pronucleus at the zygote stage. In the present
      bioassay, the following were analysed: (1) the different factors that can induce
      the formation of multipronuclear zygotes in mammals; (2) the different
      morphological patterns established according to the number of pronuclei and polar
      bodies that can be observed at the zygote stage and used to distinguish the
      origin of multipronuclear zygotes; and (3) the pattern of chromosomal segregation
      during the first mitotic division and ploidy status of the resulting
      preimplantation embryos. Such an analysis shows that the morphological criterion
      of counting the number of pronuclei and polar bodies can be misleading and should
      not be used for ascertaining the origin of tripronuclear zygotes. In addition,
      although monospermic digynic zygotes have a single sperm centromere, which likely
      organizes a single bipolar spindle during the first mitotic division, more data
      on chromosomal distribution and segregation of digynic tripronuclear zygotes
      should be collected before strategies for correction of triploidy are implemented
      in humans.

PMID- 10898293
TI  - Intrauterine growth retardation is associated with reduced cell cycle activity,
      but not myofibre number, in ovine fetal muscle.
AB  - Cellular development of muscle was studied in sheep fetuses at 85 days of
      gestation. Large and small fetuses were compared at 100, 115 and 130 days, and an
      additional group of large 130-day fetuses were studied following 7 days of
      maternal undernutrition. Myogenesis in the peroneus longus muscle was completed
      between 100 and 115 days of gestation, and myofibre number did not differ between
      small and large fetuses. The proportion of myofibre-related nuclei identified as
      entering S-phase of the cell cycle was 1.7% per hour in 85-day fetuses. In large
      fetuses, subsequent rates were relatively constant (approximately 1.5% h(-1)),
      whereas in small fetuses cell cycle activity declined with age from 1.3 to 0.9%
      h(-1), and was 0.5% h(-1) in 130-day fetuses of restricted ewes. The constant
      rate of cell cycle activity in large fetuses was associated with an increasing
      estimated rate of muscle growth (peroneus longus (mg) = 0.831 x 10(0.024 x age
      [d]), r2 = 0.98), which contrasted with slow and relatively constant muscle
      accretion in small fetuses (8.4 mg day(-1)), and slower muscle accretion at 130
      days in large fetuses from restricted ewes. Differences in DNA and RNA content in
      the semimembranosus muscle increased with age, large fetuses having 70% more
      muscle DNA, 108% more muscle RNA and 104% larger muscles than small fetuses at
      130 days (all P<0.001). The results demonstrate that myonuclei accumulation, but
      not myofibre number, is associated with fetal growth in sheep and, therefore,
      with fetal nutrition during mid to late gestation.

PMID- 10898294
TI  - Role of peripheral and central aromatization in the control of gonadotrophin
      secretion in the male sheep.
AB  - Both testosterone and its aromatized metabolite, oestradiol-17beta, are known to
      act centrally on the secretion of GnRH, but the major site of aromatization is
      not clear as aromatase activities are found in numerous tissues including brain
      and testis. Here, we tested the importance of central aromatization of
      testosterone using a non-steroidal aromatase inhibitor, fadrozole. To distinguish
      between testicular and non-testicular sites, five intact and five testosterone
      infused castrated rams (600 microg kg(-1) per 24 h for 3 days) were given four
      injections of fadrozole (i.m.; 500 microg kg(-1)) at 48, 52, 64 and 68 h relative
      to the start of testosterone infusion. Control rams (n = 5) received vehicle
      only. Fadrozole treatment decreased plasma oestradiol-17beta concentrations and
      increased the LH pulse frequency in both intact rams and testosterone-treated
      castrates, suggesting that non-testicular sites of aromatization are important in
      the control of pulsatile LH secretion. To test the importance of central
      aromatization, intact rams (n = 5) were infused into the third ventricle with
      vehicle (artificial cerebrospinal fluid) or with fadrozole (20 and 200 microg kg(
      1) per day). After two weeks, the same two doses of fadrozole were infused
      intravenously instead of intracerebrally. Central infusion of fadrozole did not
      affect plasma oestradiol concentrations but increased LH pulse frequency. Only
      the highest dose increased LH pulse frequency when infused intravenously. In
      conclusion, central aromatization is involved in the control of pulsatile LH
      secretion in male sheep.

PMID- 10898295
TI  - An ultrasound-guided procedure to administer a label of DNA synthesis into fetal
      sheep.
AB  - A novel technique was developed to deliver a bolus dose of a DNA label into the
      peritoneal cavity of fetal sheep at 85-130 days gestation. Use of markers to
      identify the site of injection in fetuses from litters up to quadruplets, and
      immunohistochemistry to detect the DNA label, 5-bromo-2'-deoxyuridine (BrdU),
      confirmed the procedure was successful in 85% of cases. Duration of the procedure
      was (mean +/- SD) 44 +/- 16 min, and recovery from anaesthesia was rapid and
      uneventful in all cases. Fetal weight was estimated with a high degree of
      accuracy (residual standard deviation (RSD) = 297 g and r2 = 0.93, P<0.001) and
      the dose of label administered (110 +/- 33 mg BrdU/kg fetal weight) was adequate
      in all cases. BrdU detected in fetal nuclei following injection into amniotic
      fluid highlights the need for positive identification of the injection site in
      timed, short-term studies, and suggests potential to further develop the
      technique to investigate cellular events in fetal sheep younger than 85 days of
      gestation. The results demonstrate that the procedure can be used to determine in
      vivo whether or not nuclei have entered the S-phase of the cell cycle.

PMID- 10898296
TI  - Quantitative vascularity of breast masses by Doppler imaging: regional variations
      and diagnostic implications.
AB  - Seventy-four biopsy proven breast masses were imaged by color and power Doppler
      imaging to evaluate vascular pattern of malignant and benign breast masses. The
      images were analyzed for vascularity. The measurements were made over the entire
      mass as well as regionally at its core, at its periphery, and in the tissue
      surrounding it. The surgical specimens were analyzed for microvessel density. The
      diagnostic performance of Doppler sonographic vascularity indices was evaluated
      by receiver operating characteristic analysis. The malignant masses were 14 to
      54% more vascular than the benign masses. Both types of masses were more vascular
      by ultrasonography than the tissue surrounding them. Whereas benign masses were
      2.2 times more vascular than the surrounding tissue, the malignant masses were
      5.0 times more vascular. In a subset of patients the regional vascularity at the
      core, periphery, and surrounding tissue by Doppler imaging exhibited a strong
      correlation (R2 > 0.9) with the corresponding histologic microvessel density
      measurements. Although the malignant masses exhibited a strong gradient in
      vascularity, core > periphery > surrounding tissue, the benign masses had
      relatively uniform distribution of vascularity. The area under the receiver
      operating characteristic curve (A(Z)) for the Doppler indices ranged from 0.56 +/
      0.07 to 0.65 +/- 0.07. A nonlinear analysis including age-specific values of
      Doppler indices improved the diagnostic performance to A(Z) = 0.85 +/- 0.06. In
      conclusion, quantitative Doppler imaging when used in combination with a
      nonlinear rule-based approach has the potential for differentiating between
      malignant and benign masses.

PMID- 10898297
TI  - Sonography of extraaxial fluid in neurologically normal infants with head
      circumference greater than or equal to the 95th percentile for age.
AB  - The goal of this study was to examine sonographically the extraaxial space in
      neurologically normal infants with occipital frontal circumference greater than
      or equal to the 95th percentile for age and correlate these dimensions with
      neurologic follow-up findings to determine a range of normal values. We thus hope
      to obviate unnecessary workup of these patients, including additional imaging or
      intervention. Our results demonstrate that for infants with a craniocortical
      width or sinocortical width less than 10 mm, the negative predictive value and
      specificity for developing a neurologic abnormality during the 55 week follow-up
      period were 94 to 100%. Thus, for neurologically normal infants with occipital
      frontal circumference greater than or equal to the 95th percentile for age and a
      head ultrasonogram that is otherwise normal, a craniocortical or sinocortical
      width of up to 10 mm can be considered within normal limits. Clinical follow-up
      evaluation is prudent, but additional imaging of these infants is not required.

PMID- 10898298
TI  - Sonographic appearance of ductal carcinoma in situ diagnosed with
      ultrasonographically guided large core needle biopsy: correlation with
      mammographic and pathologic findings.
AB  - The purpose of this study was to evaluate sonographic features of ductal
      carcinoma in situ diagnosed percutaneously at ultrasonographically guided large
      core needle biopsy. Of 619 biopsies, 203 breast carcinomas were diagnosed, of
      which nine were pure ductal carcinoma in situ. All ductal carcinoma in situ
      lesions appeared sonographically as hypoechoic masses without a pseudocapsule.
      Grade 1 lesions (n = 2; mean size, 9.5 mm), grade 2 lesions (n = 4; mean size, 18
      mm) and grade 3 lesions (n = 3; mean size, 32 mm) had means of 0, 1, and 5
      malignant sonographic features, respectively. Ductal carcinoma in situ appeared
      mammographically as a mass, with two of four grade 2 lesions and all grade 3
      lesions demonstrating suspicious microcalcifications. One grade 3 ductal
      carcinoma in situ was spiculated. In conclusion, ductal carcinoma in situ lesions
      tended to show more malignant mammographic and sonographic features as histologic
      grade and size increased.

PMID- 10898299
TI  - Elevated renal rind.
AB  - We describe the findings from a group of five infants ranging in age from 3 weeks
      to 13 months who had shock of differing causes. In each case, sonographic
      evaluation of the abdomen revealed bilateral perirenal hyperechoic bands several
      millimeters thick, surrounding a thin, hypoechoic rim of fluid. The findings were
      identified during the acute phase of each child's illness and persisted after the
      patient's condition had clinically improved, eventually resolving in the three
      surviving children. We have dubbed this sign the "elevated renal rind." We
      believe that the changes are likely secondary to systemic inflammatory mediators
      and do not reflect localized intraabdominal disease.

PMID- 10898300
TI  - Ultrasonographically guided needle biopsy of benign and malignant soft tissue and
      bone tumors.
AB  - In 65 patients an ultrasonographically guided needle biopsy was performed for
      histologic diagnosis of benign and malignant soft tissue and bone tumors. On the
      basis of the histopathologic findings, a final diagnosis could be made in 54
      cases after sonographically guided needle biopsy of the soft tissue tumor
      component. In addition, tumor grouping was possible in seven cases; however, due
      to the small volume of the biopsy specimen, further tumor differentiation proved
      to be unsuccessful. A definite diagnosis was not possible in four patients, who
      had mainly cystoid tumors; however, malignancy could be ruled out in three of
      these cases. The decisive advantage of the ultrasonographically guided needle
      biopsy procedure over what is known as a blind tumor biopsy is that the biopsy
      needle can be positioned exactly by means of imaging control. The ultrasound
      screen enables the user to monitor the biopsy procedure; multiple biopsies of
      different parts of the tumor soft tissue component can be performed using a
      single needle tract. No complications occurred in our study. Because of the far
      reaching consequences of ultrasonographically guided needle biopsy, this type of
      procedure should be performed only at tumor centers.

PMID- 10898301
TI  - Prospective imaging study of asymptomatic patellar tendinopathy in elite junior
      basketball players.
AB  - To evaluate the ability of ultrasonography to predict eventual symptoms in an at
      risk population, 52 elite junior basketball players' patellar tendons were
      studied at baseline and again 16 months later. The group consisted of 10 study
      tendons (ultrasonographically hypoechoic at baseline) and 42 control tendons
      (ultrasonographically normal at baseline). By design, all tendons were
      asymptomatic at baseline. No differences were noted between subjects and controls
      at baseline for age, height, weight, training hours, and vertical jump.
      Functional (P < 0.01) and symptomatic outcome (P < 0.05) were poorer for
      subjects' tendons than for controls. Relative risk for developing symptoms of
      jumper's knee was 4.2 times greater in case tendons than in control tendons. Men
      were more likely to develop ultrasonographic changes than women (P < 0.025), and
      they also had significantly increased training hours per week (P < 0.01) in the
      study period. Half (50%) of abnormal tendons in women became ultrasonographically
      normal in the study period. Our data suggest that presence of an ultrasonographic
      hypoechoic area is associated with a greater risk of developing jumper's knee
      symptoms. Ultrasonographic patellar tendon changes may resolve, but this is not
      necessary for an athlete to become asymptomatic. Qualitative or quantitative
      analysis of baseline ultrasonographic images revealed it was not possible to
      predict which tendons would develop symptoms or resolve ultrasonographically.

PMID- 10898302
TI  - Evaluation of bifid median nerve with sonography and MR imaging.
AB  - Bifid median nerve is an anatomic variation that may be associated with carpal
      tunnel syndrome. It is important for the surgeon to be aware of the existence of
      this condition preoperatively in order to plan the carpal tunnel release. We
      report the correlation between ultrasonographic findings and magnetic resonance
      imaging results in six patients with bifid median nerve, selected from a
      population of 294 patients with carpal tunnel syndrome, who were studied by
      ultrasonography using a high frequency transducer. Sonography showed two
      structures inside the carpal tunnel with the same pattern as the median nerve in
      all six patients. Magnetic resonance imaging confirmed the sonographic findings.
      The patients underwent open surgery, and a bifid median nerve was found. In
      conclusion, bifid median nerve is an anatomic variant that can be demonstrated
      ultrasonographically. It is important to be aware of this anomaly when planning
      carpal tunnel release surgery.

PMID- 10898303
TI  - Large endometrial polyp in a patient on long-term mifepristone therapy.

PMID- 10898304
TI  - Prenatal diagnosis of oral-facial-digital syndrome, type I.

PMID- 10898305
TI  - Prenatal diagnosis of bilateral diaphragmatic hernia: diagnostic pitfalls.

PMID- 10898306
TI  - Inflammatory pseudotumor of the liver: sonographic and computed tomographic
      features with complete regression.

PMID- 10898307
TI  - The interleukin-1 and interleukin-10 gene polymorphisms in primary sclerosing
      cholangitis: no associations with disease susceptibility/resistance.
AB  - BACKGROUND/AIMS: Although primary sclerosing cholangitis is believed to be an
      autoimmune disorder, no tissue-specific auto-antibodies have yet been identified,
      and the strongest support for an autoimmune aetiology comes from HLA-association
      studies. Three different HLA haplotypes are associated with susceptibility to the
      disease and one with protection from it. These HLA haplotypes, however, do not
      account for all of the disease risk and genes outside the HLA region may also
      have a role in disease pathogenesis. The aim of this study was to investigate,
      for the first time, polymorphic genes/sites within the interleukin-1 and
      interleukin-10 genes in a large well-characterised group of patients. METHODS:
      Ninety-six patients and 96 control subjects were studied. A single base-exchange
      polymorphism at position +3953 in the first exon of the IL-1B gene, a penta
      allelic repeat sequence in the IL-1 receptor antagonist gene (IL-1RN) and three
      single base-exchange polymorphisms at positions -592, -819 and -1082 in the IL-10
      gene promoter were determined by standard PCR-based techniques. RESULTS: Overall,
      there was no significant difference in the distribution of any of the IL-1B, IL
      1RN or IL-10 alleles or genes sequences comparing patients and controls. In
      addition, there was no difference when the patients were stratified for the
      presence and absence of the HLA DRB1*0301 (DR3) allele or concurrent inflammatory
      bowel disease. CONCLUSION: Neither the IL-1B +3953, IL-1RN microsatellites
      polymorphisms on chromosome 2q13 nor the IL-10 -592, -819, -1082 promoter gene
      polymorphisms on chromosome 1q31-32 are associated with susceptibility or
      resistance to primary sclerosing cholangitis.

PMID- 10898308
TI  - Decreased energy and phosphorylation status in the liver of lung cancer patients
      with weight loss.
AB  - BACKGROUND/AIMS: Altered energy status has been reported in the liver of tumour
      bearing animals, but data on energy status in humans are scarce. Therefore,
      bioenergetics in tumour-free liver of lung cancer patients were monitored using
      31P magnetic resonance spectroscopy (MRS) with infusion of L-alanine as a
      gluconeogenic challenge. METHODS: Twenty-one overnight-fasted lung cancer
      patients without liver metastases, with (CaWL) or without weight loss (CaWS), and
      12 healthy control subjects (C) were studied. Hepatic energy status was monitored
      before and during an i.v. L-alanine infusion of 1.4-2.8 mmol/kg + 2.8 mmol x kg(
      1) x h(-1) for 90 min by 31p MR spectroscopy. RESULTS: Baseline levels of ATP in
      WL lung cancer patients, expressed relative to total MR-detectable phosphate,
      were reduced (CaWL, 9.5+/-0.9% vs. CaWS, 12.6+/-0.8% and C, 12.4+/-0.8%; p<0.05)
      and inversely correlated with the degree of weight loss in lung cancer patients
      (r=-0.46, p=0.03). Pi/ATP ratios were increased (p<0.05), indicating reduced
      liver phosphorylation status. During L-alanine infusion, ATP levels decreased in
      all groups (p<0.05); in CaWL, ATP levels were lower at all time-points between 0
      90 min as compared to both CaWS and C (p<0.05). Pi/ATP ratios were significantly
      higher after 70-90 min of L-alanine infusion in CaWL compared to CaWS and C
      (p<0.05). CONCLUSIONS: Hepatic ATP and phosphorylation status are reduced in WL
      lung cancer patients, in contrast to WS patients and healthy subjects, and
      continue to decrease during infusion of a gluconeogenic substrate, suggesting
      impaired energy regenerating capacity in these patients.

PMID- 10898309
TI  - Hepatic arterial blood flow velocities: assessment by transcutaneous and
      intravascular Doppler sonography.
AB  - BACKGROUND/AIMS: Doppler sonography has been used to assess hepatic arterial
      perfusion in a number of published reports. However, adequate validation studies
      are available for neither the transcutaneous nor the intravascular Doppler
      approach. The aim of this comparative study was to assess hepatic arterial
      perfusion with both methods. METHODS: In 15 patients the right hepatic artery was
      examined with intravascular and transcutaneous Doppler sonography after
      calibration of Doppler devices in vitro with a thread model. The measurements
      were performed simultaneously in five and separately within 24 h in 10 patients.
      RESULTS: In vitro, the correlations between the velocities of the thread and the
      velocities as determined by intravascular (r=1.0, p<0.001) and transcutaneous
      Doppler sonography (r=1.0, p<0.001) were excellent. In vivo, the best correlation
      was found for systolic peak velocities (intravascular: 58.5+/-18.1 cm/s, mean+/
      standard deviation, transcutaneous: 58.2+/-25.2 cm/s, r=0.63, p=0.01). Although
      lower mean (intravascular: 26.5+/-7.7 cm/s, transcutaneous: 32.5+/-14.4 cm/s) and
      end-diastolic velocities (intravascular: 11.5+/-4.0 cm/s, transcutaneous: 18.4+/
      8.6 cm/s) were found with intravascular compared to transcutaneous Doppler
      sonography, significant correlations were demonstrable between results obtained
      by both methods (r=0.63, p=0.01 for mean and r=0.57, p=0.025 for diastolic
      velocities). Similarly, the calculated resistive (intravascular: 0.79+/-0.07,
      transcutaneous: 0.68+/-0.06, r=0.65, p=0.009) and pulsatility indices
      (intravascular: 1.78+/-0.47, transcutaneous: 1.26+/-0.25, r=0.55, p=0.034) were
      somewhat higher using the intravascular device, but correlated well with the
      numbers obtained by the transcutaneous approach. CONCLUSIONS: The data suggest
      that with use of different Doppler devices, systolic velocities are the most
      suitable parameter for Doppler assessment of hepatic arterial perfusion.

PMID- 10898311
TI  - Serum YKL-40 is increased in patients with hepatic fibrosis.
AB  - BACKGROUND/AIMS: YKL-40, a mammalian member of the chitinase family, is a lectin
      that binds heparin and chitin. The function of YKL-40 is unknown, but it may
      function in tissue remodelling. The aims of this study were to assess the level
      of circulating YKL-40 in patients with various kinds and degree of chronic liver
      disease and its possible relation to liver fibrosis. METHODS: Serum YKL-40 levels
      were determined by radioimmunoassay in 129 patients with suspected liver disease
      and related to histological findings and immunohistochemical staining of YKL-40
      in a liver biopsy taken simultaneously with the blood sample. RESULTS: The median
      serum YKL-40 was highest in patients with alcoholic cirrhosis (532 microg/l), in
      particular in patients with additional alcoholic hepatitis (740 microg/l).
      Patients with alcoholic cirrhosis, post-hepatitic cirrhosis (425 microg/l) and
      non-cirrhotic fibrosis (330 microg/l) had significantly higher serum YKL-40 than
      normal subjects (102 microg/l), patients with fatty liver (195 microg/l) or
      patients with viral hepatitis without fibrosis (174 microg/l). Serum YKL-40 was
      significantly (p<0.001) related to the degree of liver fibrosis with the highest
      levels in patients with moderate (466 microg/l) to severe (676 microg/l)
      fibrosis. Serum YKL-40 was also increased (p=0.018) in patients with slight
      fibrosis (270 microg/l) compared to patients without fibrosis.
      Immunohistochemical analysis demonstrated positive staining for YKL-40 antigen in
      areas with fibrosis, particularly areas with active fibrogenesis. YKL-40 staining
      was never found in hepatocytes. CONCLUSIONS: Our study indicates that the
      increased serum YKL-40 in patients with liver disease of various degree and
      aetiology seems to reflect fibrosis and fibrogenesis.

PMID- 10898310
TI  - Kupffer cell inactivation alleviates ethanol-induced steatosis and CYP2E1
      induction but not inflammatory responses in rat liver.
AB  - BACKGROUND/AIMS: Gadolinium chloride inactivates Kupffer cells and alleviates
      alcohol-induced liver lesions. We investigated the mechanism of gadolinium
      chloride protection after oral ethanol feeding. METHODS: Rats were maintained
      ethanol-intoxicated for 6 weeks by feeding ethanol in a low-carbohydrate/high-fat
      liquid diet. Macrophages were inactivated by intravenous administrations of
      gadolinium chloride. At termination, liver samples and cell lysates obtained from
      the periportal and perivenous region were analyzed for histopathology, mRNA
      expression of endotoxin-associated parameters and cytokines and for enzymes
      involved in oxidative stress. RESULTS: Ethanol treatment alone caused marked
      microvesicular/macrovacuolar steatosis and focal inflammation. Gadolinium
      significantly alleviated pathology, by reducing steatosis but not inflammation.
      Gadolinium treatment eliminated ED2 immunopositive Kupffer cells, which were
      larger and more frequent periportally. Ethanol significantly increased the mRNA
      expression of the endotoxin (LPS) receptor CD14 and the LPS binding protein LBP,
      but not that of the pro-inflammatory cytokines TNF-alpha and IL-1beta. The mRNA
      of CD14 was found to be expressed preferentially in the perivenous region, but
      gadolinium treatment had no significant effect on the expression or the
      distribution. However, gadolinium significantly moderated the ethanol induction
      of CYP2E1 and this effect correlated to the degree of steatosis. Ethanol
      increased glutathione transferase and reduced glutathione peroxidase activity,
      but these changes persisted after gadolinium treatment. CONCLUSIONS: Our results
      suggest that gadolinium chloride reduces symptoms of ALD mainly by counteracting
      steatosis, and that CD14-positive Kupffer cell populations are not involved in
      gadolinium protection. The strong correlation between pathology and CYP2E1
      induction might suggest a steatopathogenic role for this enzyme.

PMID- 10898312
TI  - Platelet-endothelial cell adhesion molecule-1 gene expression in liver sinusoidal
      endothelial cells during liver injury and repair.
AB  - BACKGROUND/AIMS: Platelet-endothelial cell adhesion molecule (PECAM)-1 is
      suggested to be critical for transmigration processes. It is a matter of debate
      whether PECAM-1 is expressed in liver sinusoids and whether it is involved in
      liver inflammation. METHODS: Indirect immunostaining and in situ hybridization
      was used to analyze PECAM-1 gene expression in normal and diseased rat and human
      livers as well as in isolated rat sinusoidal endothelial cells (SECs), hepatic
      stellate cells and hepatocytes. At various time points after the administration
      of CCl4 (6 h, 24 h, 48 h, and 72 h), PECAM-1 gene expression was analyzed in
      livers and in SECs by immunostaining, and Northern blot analysis. RESULTS: In
      normal rat or human livers PECAM-1 immunoreactivity was detected along the
      sinusoids in a pattern similar to ICAM-1 staining. PECAM-1 specific transcripts
      were detected in freshly isolated and cultured SECs. After a single CCl4
      administration, PECAM-1 immunoreactivity did not increase along the sinusoids in
      contrast to the early increase of ICAM-1. Northern blot analysis indicated that
      PECAM-1 expression in liver tissue and in isolated SECs does not increase after a
      single administration of CCl4, whereas ICAM-1 steady-state level increased after
      6 h. In diseased human livers PECAM-1 was detectable along the sinusoids, within
      inflammatory infiltrates and within fibrotic septa. Neither in acutely nor
      chronically diseased human livers was an obvious increase of PECAM-1
      immunoreactivity detectable. CONCLUSIONS: PECAM-1 is expressed by SECs. In
      contrast to ICAM-1, PECAM-1 transcript level is not enhanced during liver damage.

PMID- 10898313
TI  - Hepatocellular carcinoma in patients with acute hepatic porphyria: frequency of
      occurrence and related factors.
AB  - BACKGROUND/AIMS: Previous retrospective studies have suggested an association
      between hepatocellular carcinoma and acute hepatic porphyrias. The incidence, the
      relative risk, the characteristics and the outcome of primary liver cancer were
      prospectively evaluated in patients with acute hepatic porphyrias; the molecular
      mechanism of carcinogenesis in these patients was also pointed out. METHODS: A
      cohort of 650 patients with acute hepatic porphyria was followed over 7 years.
      Standardized rate ratio was used to measure the relative risk of primary liver
      cancer after indirect standardization. Morphological and clinical aspects of
      primary liver cancer were investigated, and survival rates were calculated using
      the Kaplan-Meier method. Common etiological factors involved in liver
      carcinogenesis were screened. Excretion rates of porphyrin precursors, serum
      melatonin levels and mutations in the genes encoding for heme biosynthetic
      enzymes were studied. RESULTS: Hepatocellular carcinoma was found in four
      symptomatic and three asymptomatic patients (four female, three male). The
      overall standardized rate ratio was 36 (95% CI: 14-74). The 5-year disease-free
      survival was 43% in patients with hepatocellular carcinoma. Usual risk factors
      for primary liver cancer were not confounding factors. Hepatocellular carcinoma
      was not related to specific heme biosynthesis gene mutations. Heme precursors
      were significantly increased in porphyric patients with hepatocellular carcinoma,
      and serum melatonin levels were low. CONCLUSIONS: Acute hepatic porphyrias are
      risk factors for hepatocellular carcinoma. Hepatic porphyrias should be sought in
      patients with hepatocellular cancer without obvious etiology, and a periodic
      screening for hepatocellular carcinoma should be evaluated in these patients.
      Genes encoding for heme biosynthetic pathway may not act as tumor suppressor
      genes. Chronic increased levels of delta aminolevulinic acid could lead to the
      generation of free radicals and subsequently to hepatic carcinogenesis.

PMID- 10898314
TI  - The compensatory hyperplasia (liver regeneration) following ligation of a portal
      branch is initiated before the atrophy of the deprived lobes.
AB  - BACKGROUND/AIMS: In rats, partial ligation of portal branches produces atrophy of
      the deprived lobes and hypertrophy of the intact lobes. The hepatocyte
      proliferation observed in the nondeprived lobes is viewed as a compensatory
      hyperplasia, implying that the atrophy somewhat precedes the initiation of the
      proliferative response. As this has not been demonstrated, the time course and
      magnitude of those two sequences of events were investigated and compared with
      the well-defined response to a partial hepatectomy. METHODS: The portal branch
      feeding the anterior liver lobes was ligated in male Wistar rats. One-third and
      two-thirds partial hepatectomies were also performed. Liver weight, the
      aminopyrine demethylation rate, an index of the liver mass, the DNA content and
      various indices of cell proliferation were measured. RESULTS: Resection of the
      anterior lobes (PH) or ligation of their portal blood supply (PBL) induced a
      marked DNA synthesis in the posterior lobes (3H-thymidine incorporation) reaching
      its maximum 24 h after both interventions. This response can even be accelerated
      by performing a sham operation 6 h before the PBL. The process leading to DNA
      synthesis thus seems to start as early after PBL as after a PH, although the
      weight of the liver or the aminopyrine demethylation rate was nearly unchanged 2
      h following PBL. The initiation of the proliferative response clearly precedes
      and is thus independent of the reduction of the liver mass. On the other hand,
      the progressive reduction of the liver mass seems to determine the magnitude of
      the proliferative response, which is, for instance, greatly increased following
      the excision of the deprived lobes, as late as 10 h after ligation of their
      portal branches. In comparison with the results obtained after a 113 PH, the peak
      of DNA synthesis at the 24th hour is greater than predicted by the liver weight
      loss, but this parameter could underestimate the reduction of the functional
      liver mass. CONCLUSION: The proliferative response following a PBL can be divided
      into an early phase occurring independently of the reduction of the liver mass
      and a late phase controlled by this reduction. The paradox of the proliferative
      response which seems to start before the atrophy to be compensated is resolved by
      this hypothesis.

PMID- 10898315
TI  - Plasma fucosyltransferase activity in patients with hepatocellular carcinoma,
      with special reference to correlation with fucosylated species of alpha
      fetoprotein.
AB  - BACKGROUND/AIMS: Our previous results showed that the percentage of fucosylated
      species of alpha-fetoprotein (AFP) in total AFP, fucosylation index, was a very
      useful diagnostic tool to distinguish AFP due to hepatocellular carcinoma from
      AFP due to non-neoplastic liver diseases. On the other hand, alpha1-6 fucosyl
      transferase (alphaFT) catalyzes the addition of fucose from GDP-fucose through an
      alpha1-6 linkage to the reducing end of N-acetylglucosamine residue of N-linked
      oligosaccharides of glycoproteins. However, the biological and clinical
      significance of alphaFT in patients with hepatocellular carcinoma is not fully
      understood. In the present study, we measured alphaFT activity to elucidate the
      enzymatic background of fucosylated species of AFP in hepatocellular carcinoma.
      METHODS: Plasma samples from 84 cases of hepatocellular carcinoma, 40 of liver
      cirrhosis, 40 of chronic hepatitis and 30 of normal controls, and 26 paired
      samples of hepatocellular carcinoma and surrounding noncancerous tissues were
      enrolled in the present study. AlphaFT activity was measured by high performance
      liquid chromatography with a synthesized fluorescence-labeled glycopeptide with
      an asialoagalactobiantennary sugar chain as a substrate in the presence of GDP
      fucose. RESULTS: Plasma alphaFT activities (mean+/-SD, pmol/ml/h) in patients
      with hepatocellular carcinoma, liver cirrhosis, chronic hepatitis and normal
      controls were 435+/-271, 490+/-290, 590+/-209 and 380+/-133, respectively.
      AlphaFT levels in hepatocellular carcinoma and chronic liver diseases were
      increased compared with that in normal controls. A statistically significant
      positive correlation was observed between plasma alphaFT activity and
      fucosylation index of AFP (r=0.34, p= 0.0032) in 60 patients with hepatocellular
      carcinoma, in which increments of serum AFP were observed. When the tentative
      cutoff value of fucosylation index was set at 18%, which corresponded to the
      cutoff value to discriminate between hepatocellular carcinoma and non-neoplastic
      liver diseases in our previous study, the plasma alphaFT activity in
      hepatocellular carcinoma patients whose fucosylation index was more than 18%
      (n=32, 523+/-324 pmol/ml/h) was higher than that in hepatocellular carcinoma
      patients whose fucosylation index was equal to or less than 18% (n=28, 383+/-229)
      (p=0.055). An increment of the plasma levels of alphaFT occurred in accordance
      with an advancement of hepatocellular carcinoma stages. Tissue aFT activity in
      hepatocellular carcinoma (175+/-178 pmol/mg/h) was higher than those in
      surrounding noncancerous liver (144+/-134) and in normal liver (79+/-19). The
      mean alphaFT activities in well-, moderately- and poorly-differentiated
      hepatocellular carcinoma were 38+/-0.7, 177+/-182 and 219+/-189, respectively,
      and they tended to increase with dedifferentiation in hepatocellular carcinoma
      tissues. CONCLUSIONS: The present study indicates that alphaFT is responsible for
      the formation of the fucosylated species of AFP in hepatocellular carcinoma and
      suggests that the measurement of alphaFT provides a possible aid in the
      evaluation of the degree of advancement in patients with hepatocellular
      carcinoma.

PMID- 10898316
TI  - A randomized clinical trial comparing autologous blood clot and gelfoam in
      transarterial chemoembolization for inoperable hepatocellular carcinoma.
AB  - BACKGROUND/AIM: Inoperable hepatocellular carcinoma is common in Asia and is
      usually treated with repeated transarterial chemoembolization. Gunji et al.
      showed better survival and fewer complications with autologous blood clot as
      compared with gelfoam used for embolization. Our aim was to compare the effect of
      blood clot versus gelfoam. METHODS: We conducted a prospective randomized trial
      in 100 patients with inoperable hepatocellular carcinoma, and compared the side
      effects and cumulative survival in the two groups. Cox's proportional hazard
      model was used to study the prognostic factors. RESULTS: The diameter of the main
      tumor was 7.9+/-4.6 cm. Our study did not show additional beneficial effects of
      blood clot. The proportion of side effects was similar and the common ones
      included fever, pain and vomiting. Though the hepatic artery remained patent for
      a longer period with blood clot (p=0.061), there was no difference in survival
      (p=0.129 for Okuda I disease and p=0.388 for Okuda II disease). Subgroup analysis
      showed longer survival in patients with vascular occlusion (p=0.034 for Okuda I
      and p=0.029 for Okuda II disease). The independent factors of survival were sex,
      Child's class, Okuda stage, tumor type and presence of metastases. CONCLUSION:
      This study showed no additional benefits of blood clot in patients with
      inoperable hepatocellular carcinoma, in Okuda I and II disease. The longer
      survival in patients with vascular occlusion suggested that the damage to normal
      liver tissue by planned periodic transarterial chemoembolization may outweigh its
      benefit in later sessions of repeated TACE in certain patients.

PMID- 10898317
TI  - Treatment of mice with EGF and orthovanadate activates cytoplasmic and nuclear
      MAPK, p70S6k, and p90rsk in the liver.
AB  - BACKGROUND/AIMS: Although signal transduction pathways activated by EGF have been
      extensively studied in cultured cells, few such studies have been done in whole
      animals. In this study, activation of hepatic kinases, phosphatases, and DNA
      binding activity of AP-1 was examined after intraperitoneal injections of either
      EGF or sodium orthovanadate into mice. METHODS: Cytoplasmic and nuclear proteins,
      extracted from isolated hepatocytes or whole liver tissue, were
      immunoprecipitated with either anti-ERK1/2, anti-70S6k, or anti-p90rsk antibodies
      and kinase activities were measured using specific substrates. Kinase protein
      levels was evaluated by Western blot analysis. AP-1 DNA binding activity was
      measured by electrophoretic mobility shift assay. RESULTS: Systemic
      administration of EGF induced simultaneous increase in the activities of
      cytoplasmic and nuclear MAPK, p70S6k, and p90rsk. MAPK and p70S6k were more
      potently activated in the cytosol while p90rsk activation was more pronounced in
      the nucleus. Orthovanadate also activated these kinases but to a much lesser
      degree than EGF. In vitro phosphatase assays showed that neither EGF nor
      orthovanadate induced measurable changes in phosphatase activities. EGF, but not
      orthovanadate, activated nuclear AP-1 DNA-binding activity in intact liver,
      indicating that activation of MAPK, p70S6k, and p90rsk by orthovanadate is not
      sufficient to activate this transcription factor. CONCLUSION: These observations
      provide groundwork for future studies to examine the role of EGF-induced kinase
      cascades and transcription factors in liver regeneration and other growth factor
      mediated hepatic processes.

PMID- 10898318
TI  - Transduction of hepatocellular carcinoma (HCC) using recombinant adeno-associated
      virus (rAAV): in vitro and in vivo effects of genotoxic agents.
AB  - BACKGROUND/AIMS: Adeno-associated virus (AAV) is an attractive tool for gene
      therapy. Here we investigated the in vitro and in vivo transduction of
      hepatocellular carcinoma (HCC) cells by an AAV vector and the efficacy of
      different strategies to enhance the transduction of the tumor. METHODS:
      Transduction efficiency was determined by analyzing AAV-mediated beta
      galactosidase gene (rAAV/lacZ) expression. RESULTS: Adenovirus help or
      pretreatment of HCC cells with y-irradiation or with the topoisomerase inhibitor
      etoposide resulted in marked enhancement of cell transduction in vitro. In vivo
      studies in nude mice with subcutaneous HCC tumors showed that HCC cells were not
      transduced by AAV vector alone. However, co-infection of the tumor with
      adenovirus allowed an efficient expression of the reporter gene but only at the
      sites of vector injection. Previous gamma-irradiation of subcutaneous tumors with
      1800 rad was able to improve transduction of HCC cells (up to 30%) using
      recombinant AAV. Continuous i.p. infusion of etoposide in buffalo rats harboring
      HCC tumors in the liver resulted in transduction of normal liver tissue and also
      of very small neoplastic lesions (<2 mm) but no transduction was observed in
      tumors bigger than 2 mm. To analyze this phenomenon we determined etoposide
      concentration in hepatic tissue. Our results revealed high concentrations of the
      drug in non-tumoral tissue but almost undetectable levels in big tumor nodules.
      CONCLUSIONS: Our results indicate that while both radiotherapy and etoposide
      enhance transduction of tumor cells by rAAV in vitro, only radiotherapy increases
      tumor transduction in vivo. Our data suggest the existence of a barrier which
      limits in vivo the diffusion of chemotherapeutic agents to well-established HCC
      nodules.

PMID- 10898319
TI  - Prognosis of alpha-1-antitrypsin deficiency-related liver disease in the era of
      paediatric liver transplantation.
AB  - BACKGROUND/AIM: Alpha-1-antitrypsin deficiency (alpha1ATD) is the commonest
      metabolic disease leading to liver transplantation (LT) in children.
      Approximately 10-15% of the PiZZ population develops liver disease. Five percent
      of them will require LT within the first 4 years of life. This study aimed to
      investigate the prognosis of the liver disease associated with PiZZ alpha1ATD in
      the era of liver transplantation and to determine predictors of outcome. METHODS:
      We reviewed retrospectively the clinical notes of 97 consecutive patients
      referred from January 1989, when LT became routinely available in our Unit, to
      July 1998. RESULTS: Of 26 (27%) patients who developed end-stage liver disease,
      24 have been transplanted and two are waiting for LT. Twenty-one (81%) of these
      patients presented with neonatal hepatitis at a median age of 2.1 months. Of 71
      (73%) children who have not required LT, 61 (86%) presented with neonatal
      hepatitis at a median age of 1.6 months. Among infants with neonatal hepatitis
      who required LT, 18 out of 21 (86%) had jaundice for more than 6 weeks compared
      with 34 of 61 (56%) who survived without LT (p<0.01). Children requiring LT had
      higher aspartate aminotransferase (AST) at presentation (p<0.0001) and both
      higher AST and gamma-glutamyl transferase (GGT) at 6 months (p<0.001), 1-year
      (p<0.0003) and 5-year (p<0.01) follow up when compared to those who are well
      without LT. Furthermore, children who developed end-stage liver disease more
      frequently had severe bile duct reduplication (p<0.01), severe fibrosis (p<0.03)
      with bridging septa (p<0.02) and established cirrhosis (p<0.04) in the initial
      liver biopsy. Ninety-five of the 97 children (98%) are currently alive; two died
      after LT. CONCLUSIONS: The advent of liver transplantation has significantly
      improved the prognosis of liver disease associated with PiZZ alpha1ATD. Duration
      of jaundice, severity of histological features and biochemical abnormalities
      predict outcome at an early stage of the disease.

PMID- 10898320
TI  - Decorin and actin expression and distribution in patients with chronic hepatitis
      C following interferon-alfa-2b treatment.
AB  - BACKGROUND/AIMS: Chronic hepatitis C can lead to cirrhosis and hepatocellular
      carcinoma. Interferon-alfa therapy may prevent the progression of the disease.
      The expressions of decorin and alfa-smooth muscle cell actin of the extracellular
      matrix play a central role in liver fibrosis. We set out to assess the
      expressions of these proteins in chronic hepatitis C patients, and to evaluate
      how they can be modified by interferon-alfa therapy. METHODS: Twenty chronic
      hepatitis C patients received interferon-alfa-2b therapy for 6 months (group I)
      or 12 months (group II). Liver biopsy samples were taken before and after the
      therapy. The alfa-smooth muscle actin-positive cells were determined with a
      monoclonal antibody, and decorin expression was detected with a polyclonal
      antibody. The cells were evaluated with a semiquantitative scoring method. For
      statistical analysis, non-parametric methods were used. RESULTS: Before the
      therapy, alfa-smooth muscle actin-labeled cells and marked decorin expression
      were present throughout all the acinar zones. Interferon-alfa-2b therapy resulted
      in significant decreases in both the number of alfa-smooth muscle actin-positive
      cells and the decorin expression. The alfa-smooth muscle actin-positive cells and
      decorin expression correlated with the histological activity index (R=0.72,
      p<0.03, R=0.68, p<0.05). CONCLUSIONS: This study demonstrates that a large number
      of alfa-smooth muscle actin-positive cells and a marked decorin expression are
      frequent findings in chronic hepatitis C. Treatment with interferon-alfa-2b for
      12 months reduced the number of labeled cells and the decorin expression. The
      results suggest that interferon-alfa-2b is capable of interfering with
      fibrogenesis in an early and presumably still reversible phase of chronic
      hepatitis C.

PMID- 10898321
TI  - Does HIV-infection influence the response of chronic hepatitis C to interferon
      treatment? A French multicenter prospective study. French Multicenter Study
      Group.
AB  - BACKGROUND/AIM: The aim of this prospective study was to compare the response to
      alfa-interferon treatment of chronic hepatitis C in two groups of patients:
      coinfected with human immunodeficiency virus (HIV) (G I) or not (G II). METHODS:
      One hundred and fifty-three patients with chronic hepatitis C had been enrolled
      in 30 French liver units or infectious diseases units between May 1992 and
      January 1995 (G I: 76, G II: 77) to receive alfa-2a interferon: 3 MU thrice
      weekly for 6 months. RESULTS: One hundred and twenty-seven patients (G I: 63, G
      II: 64) fulfilled all criteria for analysis. The two groups were comparable for
      all demographic data, while significantly more severe biological and histological
      (p=0.001) parameters attested to more serious hepatitis among HIV-HCV coinfected
      patients. HCV viremia was higher among HIV-coinfected patients (p=0.0169), while
      genotype repartition was identical among the two groups (more than 52% of
      genotype 1, more than 31% of genotype 3). ALT normalization was, respectively, (G
      I/G II) obtained in 17.46%/26.56% (not significant) of patients at the end of
      treatment and in 11.11%/12.5% (not significant) of patients after 6 months of
      follow-up. In a multivariate analysis, GGT level before therapy (relative risk
      2.1, confidence interval 1.1-5.8) and body surface area (relative risk 1.9,
      confidence interval 1.1-3.7) were the variables independently associated with the
      response to alfa-interferon treatment (higher GGT and more elevated body surface
      area were associated with a risk of non-response). CONCLUSION: In our study HIV
      infection did not affect the alfa-interferon treatment response of chronic
      hepatitis C, and response could be achieved among HIV-coinfected patients.
      Present therapeutic anti-HCV schedules need to be proposed to HIV-HCV coinfected
      patients before severe immunosuppression occurs. On the other hand, more severe
      biological and histological parameters were observed among HIV-HCV coinfected
      patients, which suggests a need to study whether HIV infection is associated with
      a worsening course of chronic hepatitis C.

PMID- 10898322
TI  - Famciclovir in chronic hepatitis B: results of a dose-finding study.
AB  - BACKGROUND/AIMS: Famciclovir, an orally available nucleoside analogue with potent
      in vitro activity against HBV, is being investigated for treatment of chronic
      hepatitis B. METHODS: A dose-finding study was conducted in patients with
      hepatitis B e antigen present in serum. Patients received famciclovir 125 mg, 250
      mg, 500 mg three times daily (tid) or placebo for 16 weeks, followed by 8 months
      post-treatment observation, and 16 weeks open-label treatment. More than 90% of
      patients had previously received alpha-interferon or had baseline characteristics
      indicating a high likelihood of poor response to alpha-interferon. RESULTS:
      Famciclovir induced rapid, dose-dependent suppression of viral replication and
      reduction in alanine aminotransferase (ALT), with greatest efficacy in the 500-mg
      tid treatment group. HBV DNA reduction was maintained throughout the treatment
      period. ALT also steadily declined during the treatment period. Approximately 40%
      of patients with pretreatment ALT>upper limit of normal (ULN) receiving
      famciclovir 500 mg tid, experienced sustained normalization of ALT at the end of
      the 8-month follow-up. Anti-HBe seroconversion occurred more frequently in
      patients receiving famciclovir 500 mg tid compared with placebo (p=0.04).
      Famciclovir was generally well tolerated; the incidence of adverse events was
      comparable to placebo. Exacerbation of liver disease or serious ALT flares were
      not observed. CONCLUSION: Famciclovir 500 mg three times daily may offer an
      alternative to alpha-interferon for treatment for chronic hepatitis B. Anti-HBe
      seroconversion in the famciclovir 500-mg tid group suggests that 16 weeks
      treatment has the potential for HBV clearance. Further studies with a longer
      treatment duration are warranted.

PMID- 10898323
TI  - Effects of delayed freezing of liver biopsies on the detection of hepatitis C
      virus RNA strands.
AB  - BACKGROUND/AIMS: There are no data about the influence of handling conditions of
      liver biopsies on the integrity of viral RNAs. We studied the influence of the
      time delay between obtaining and freezing the liver biopsy on the stability of
      intrahepatic positive and negative hepatitis C virus RNA (HCV-RNA) strands.
      METHODS: Liver samples from 30 anti-HCV patients were included. For each case,
      one portion of the liver biopsy (first sample) was immediately frozen (20-28 s),
      while the other section (second sample) was kept at room temperature (1-30 min)
      before freezing. Each experimental time point was performed in triplicate using
      liver samples from three different patients. Semi-quantitative analysis of the
      positive and negative HCV-RNA strands and of the al-antitrypsin mRNA was
      performed by a Tth-based reverse-transcription polymerase chain reaction.
      RESULTS: A significant time-related decrease in both positive (r=-0.8412,
      p=0.001) and negative (r=-0.8539, p=0.001) HCV-RNA strand titres was found in the
      second liver fractions. There were no appreciable changes in RNA titres in those
      samples frozen after less than 3 min. The RNA titres decreased in all but two
      samples incubated for 4-30 min. Thus, 3/15 (20%) and 7/11 (64%) of these samples
      lost positive and negative HCV-RNA strands, respectively. Alpha-1-antitrypsin
      mRNA titres decreased significantly (r=-0.8935, p=0.01) in those samples kept at
      room temperature for more than 4 min. CONCLUSION: Freezing of liver samples
      immediately after extraction is crucial to avoid false negative HCV-RNA detection
      results, especially for the antigenomic RNA strand.

PMID- 10898324
TI  - Alcohol-induced fatty liver and inflammation: where do Kupffer cells act?

PMID- 10898325
TI  - Recombinant adenoassociated virus in cancer gene therapy.

PMID- 10898326
TI  - Hepatic encephalopathy in chronic liver disease: a clinical manifestation of
      astrocyte swelling and low-grade cerebral edema?

PMID- 10898327
TI  - Hydatid disease--Echinococcus granulosus infection.

PMID- 10898328
TI  - Lamivudine in the last 4 weeks of pregnancy to prevent perinatal transmission in
      highly viremic chronic hepatitis B patients.

PMID- 10898329
TI  - Rapid onset of hematotoxic effects after interferon alpha in hepatitis C.

PMID- 10898330
TI  - Molecular mechanisms of osteolytic bone metastases.
AB  - BACKGROUND: Breast carcinoma commonly metastasizes to the skeleton in patients
      with advanced disease to cause bone destruction and the associated pain,
      hypercalcemia, fracture, and nerve-compression syndromes. In this scenario, the
      bone destruction is mediated by the osteoclast. Tumor-produced parathyroid
      hormone-related protein (PTHrP), a known stimulator of osteoclastic bone
      resorption, is a major mediator of the osteolytic process. Transforming growth
      factor beta (TGFbeta), which is abundant in bone matrix and is released as a
      consequence of osteoclastic bone resorption, may promote breast carcinoma
      osteolysis by stimulating PTHrP production by tumor cells. METHODS: Stable breast
      carcinoma MDA-MB-231 cell lines were constructed that expressed mutant TGFbeta
      receptors, Smad proteins, or estrogen receptor (ER)-alpha and were used to
      determine the role of TGFbeta in modulating tumor production of PTHrP. These
      stable cell lines were applied to a mouse model of human breast carcinoma
      metastases to the bone to dissect the molecular mechanisms responsible for
      osteolytic bone metastases. RESULTS: TGFbeta promoted the development and
      progression of osteolytic bone metastases by inducing tumor production of PTHrP,
      the effect of which was mediated through the Smad signaling pathway. PTHrP
      stimulated osteoclastic bone resorption by increasing osteoblast production of
      the receptor activator of nuclear factor K B (RANK) ligand and decreasing
      osteoblast production of osteoprotegerin (OPG). A constitutively active ER-alpha
      mutation (Tyr537Asn), identified from a human bone metastases, when it was
      expressed in human breast carcinoma cells, caused increased production of PTHrP.
      TGFbeta significantly enhanced the ER-alpha-mediated transcriptional activity
      induced by ER-alpha (Tyr537Asn), and this resulted in further stimulation of
      PTHrP production. CONCLUSIONS: These data indicate a central role for TGFbeta in
      the pathogenesis of osteolytic bone metastases from breast carcinoma by 1) the
      induction of PTHrP through the Smad signaling pathway and 2) the potentiation of
      ER-alpha-mediated transcription induced by a constitutively active ER-alpha.
      Understanding the mechanisms of osteolysis at a molecular level will generate
      more effective therapeutic agents for patients with this devastating complication
      of cancer.

PMID- 10898331
TI  - Bone tissue specific transcriptional control: options for targeting gene therapy
      to the skeleton.
AB  - BACKGROUND: The transplantation of multipotential bone marrow cells containing
      bone tissue specific promoter-controlled transgenes provides an efficacious
      approach to deliver therapeutic gene expression to osteoblasts for the treatment
      of patients with bone disorders or tumor metastasis to the skeleton. The
      specificity of tissue-restricted gene therapy can be refined by utilization of a
      31-amino-acid segment of the hematopoietic and osteogenic AML/CBF transcription
      factors that direct the regulatory proteins to subnuclear sites that support gene
      expression. METHODS: Unfractionated adherent bone marrow cells from transgenic
      mice constructed with the proximal 1.7 kb of the osteocalcin gene promoter fused
      to a CAT reporter were transplanted by intravenous infusion. Engraftment and
      expression at the single-cell level within the context of tissue organization was
      established by immunohistochemistry using an anti-CAT antibody. Sequences that
      support the intranuclear trafficking of AML/CBF transcription factors to
      subnuclear sites that support transcription were determined by the expression and
      visualization of mutated and epitope tagged AML/CBF proteins. RESULTS:
      Immunohistochemical staining of an extensive series of tissue sections from mice
      posttransplantation using an anti-CAT antibody indicated that CAT-positive
      osteoblasts and osteocytes were present in bone sections. These findings indicate
      that donor bone marrow-derived cells engraft in bone tissue in an environment
      that supports maturation to the developmental stage at which a bone specific
      osteocalcin promoter is transcriptionally active. Characterization of functional
      domains in AML/CBF transcription factors has established that there are at least
      two regulated events that are required for targeting the factors to
      transcriptionally active nuclear domains: A nuclear localization signal in the
      amino terminal region controls nuclear import and retention, and a nuclear matrix
      targeting signal in the carboxyl region controls association with nuclear matrix
      linked sites where transcription occurs. CONCLUSIONS: The specificity of
      hematopoietic and bone phenotypic promoters, together with the additional level
      of specificity inherent in the AML/CBF family of hematopoietic and osteogenic
      intranuclear targeting signals, offers viable options for constructing gene
      therapy regimens that are targeted to the skeleton for the control of metastatic
      disease. It is realistic to anticipate that, as additional parameters of gene
      regulatory mechanisms are defined, particularly components of transcriptional
      control that are operative within a three-dimensional context of nuclear
      architecture, opportunities for enhancing the effectiveness of treating patients
      with tumors that metastasize to bone will be extended.

PMID- 10898332
TI  - Molecular basis of the spectrum of skeletal complications of neoplasia.
AB  - BACKGROUND: Neoplasia may produce a spectrum of dysregulatory effects on bone and
      mineral metabolism. The range of these effects and the known molecular mechanisms
      causing them are reviewed. METHODS: The current review is mainly based on
      previously published scientific reports from North America, Europe, and Japan
      that were identified from references in the literature. RESULTS: Osteolysis is
      the most common skeletal manifestation of neoplasia and may be focal or
      generalized. When tumors release abundant parathyroid hormone-related peptide
      (PTHrP) into the circulation, this may act as an endocrine substance to produce
      generalized osteopenia and, ultimately, hypercalcemia. PTHrP also may act in a
      paracrine manner to enhance focal osteolysis associated with metastasis and to
      generate hypercalcemia. The increased circulating PTHrP in tumor states also can
      augment serum calcium by renal mechanisms. PTHrP may contribute to focal
      osteolysis by tumor metastases, even in the absence of hypercalcemia. Strategies
      to reduce PTHrP production or PTHrP signaling, therefore, may be useful to treat
      the tumor-induced bone resorption induced both in hypercalcemic and
      nonhypercalcemic states. The most commonly used intervention, bisphosphonates,
      targets the osteoclast directly. Although osteolytic lesions generally occur with
      some degree of reactive new bone formation, osteoblastic lesions may be
      particularly abundant in association with certain tumors, such as prostate
      carcinoma. The mechanisms underlying these lesions remain unknown; however, a
      variety of osteoblast growth factors may contribute. These include the urokinase
      system, which may have growth factor activity as well as enzymatic activity.
      Finally, osteomalacia may be a manifestation of tumors either through accelerated
      bone formation with insufficient mineralization or through the production of a
      phosphaturic substance. CONCLUSIONS: Elucidation of the mechanisms underlying the
      spectrum of skeletal manifestations of neoplasia is yielding important insights
      into both tumor diagnosis and patient management.

PMID- 10898333
TI  - Parathyroid hormone-related protein as a potential target of therapy for cancer
      associated morbidity.
AB  - BACKGROUND: Proinflammatory cytokines are involved in the genesis of cancer
      associated cachexia. Parathyroid hormone-related protein (PTHrP) is the causative
      agent in humoral hypercalcemia of malignancy (HHM) and is frequently secreted
      from various kinds of solid tumors as well as from adult T-cell
      leukemia/lymphoma. PTHrP, like PTH, acts on PTH receptor type 1 (PTH1R).
      Activation of PTH1R may lead to stimulation of secretion of proinflammatory
      cytokines. It is expected, therefore, that PTHrP constitutes a key factor in the
      activation of the proinflammatory and cachectogenic cytokine network and
      consequently in the development of cachexia in patients with cancer. METHODS: Two
      groups of cancer-bearing patients of similar clinical backgrounds were enrolled.
      Plasma concentrations of PTHrP and cytokines were measured with immunoradiometric
      assay and radioimmunoassay, respectively. Cancer tissues from patients with HHM
      were transplanted into nude mice or nude rats. The effects of humanized antihuman
      PTHrP antibody were examined. RESULTS: In clinical studies, Group B patients
      (with elevated plasma PTHrP), compared with Group A patients (with normal plasma
      PTHrP), tended to exhibit higher plasma levels of tumor necrosis factor (TNF)
      alpha (P = 0.13), interleukin (IL)-5 (P = 0.08), and IL-8 (P = 0.08), and had
      significantly higher levels of IL-6 (P = < or =0.01). The levels of TNF-alpha and
      IL-6 correlated with those of PTHrP. In animal studies, the antibody caused a
      prompt and sustained decline in serum calcium. This response was accompanied by
      improvements in food intake, drinking, body weight gain, and general behavior. It
      also ameliorated the suppression of serum ADH. When those effects were compared
      with those induced either by bisphosphonate or calcitonin, it turned out that not
      all of the beneficial effects of the antibody were directly correlated with the
      depression of blood calcium. CONCLUSIONS: PTHrP is a promising molecular target
      for the development of a novel mode of treatment for patients with cancer
      associated morbidity.

PMID- 10898334
TI  - Pathophysiologic interactions in skeletal metastasis.
AB  - BACKGROUND: This review summarizes evidence that the formation of bone metastases
      is the result of multiple synergistic cellular and molecular interactions between
      metastatic cells and the unique microenvironment in bone. METHODS: Molecular
      technologies have been used to detect cancer cells in bone and to define their
      genotypic and phenotypic properties. Bone organ cultures have been employed to
      analyze the ability of tumor cells to modulate bone resorption and to study the
      effects of resorption products on the phenotypic properties of cancer cells.
      Experimental models of bone metastasis provide the ability to examine the effects
      of modulating specific host or tumor properties in vivo by quantifying their
      effects on the formation of bone tumors. RESULTS: By means of the blood stream,
      cells from many common neoplasms seed bone marrow as an early clinical event. The
      subsequent growth of these cells into clinically significant metastatic lesions
      is associated with their ability to stimulate bone resorption through osteoclasts
      and macrophages or through a direct action on bone. In turn, the products of bone
      resorption, which include matrix-derived growth factors, act on the tumor cells
      to stimulate the expression of properties that promote their metastatic
      competence. These include the induction of integrin adhesion molecules, the
      stimulation of cell motility and chemotaxis, the enhanced expression of matrix
      metalloproteinases, and the stimulation of tumor cell growth. CONCLUSIONS: The
      interdependency of tumor cells and bone was recognized by Steven Paget over 100
      years ago, and it provides a rational basis for the development of current
      therapeutic strategies against bone metastasis.

PMID- 10898335
TI  - Biochemical markers and skeletal metastases.
AB  - BACKGROUND: Skeletal metastases are common occurrences in patients with
      malignancies such as breast and prostate carcinoma, but they are difficult to
      diagnose nonradiologically, and treatment is difficult to follow clinically.
      Recent developments suggest that biochemical markers of bone remodeling, such as
      the bone collagen breakdown product N-telopeptide and the bone formation marker
      known as bone specific alkaline phosphatase, hold great promise as clinical tools
      for the management of patients with metastatic bone disease. METHODS: Serum
      levels of the bone formation marker known as bone specific alkaline phosphatase
      (BAP), along with serum levels of the bone collagen breakdown product
      carboxyterminal telopeptide of Type I collagen (ICTP) and urine levels of
      pyridinoline (PYD), deoxypridinoline (DPD), and N-telopeptide (NTx), were
      measured in a large cohort of patients with newly diagnosed or progressive cancer
      of the breast, prostate, lung, and other sites. Bone marker levels were
      correlated with the presence or absence of bone scan-documented metastases;
      metastatic disease extension in terms of the number of skeletal sites involved;
      and the type of lesion, whether blastic or lytic. Sites examined included the
      pelvis, spine, skull, ribs, and long bones. RESULTS: All of the bone markers
      examined, including BAP and NTx, were abnormally elevated in a high proportion of
      patients with confirmed metastases to bone. Urine NTx levels and bone specific
      alkaline phosphatase were significantly correlated with the number of skeletal
      sites involved, and a significant correlation between marker level and extent of
      skeletal involvement was also observed. In addition, both markers were higher in
      patients with a blastic disease presentation than in patients with osteolytic
      lesions. CONCLUSIONS: Biochemical markers of bone resorption and bone formation
      are abnormally raised in the blood and urine of patients with metastatic bone
      disease. Markers of bone collagen breakdown, such as N-telopeptide, as well as
      markers of osteoblast function, such as bone specific alkaline phosphatase,
      appear to be of use in assessing and managing patients with malignancies that
      metastasize to bone. In this study, both NTx and BAP showed a significant
      correlation with both the presence of bone metastases and the extent of skeletal
      involvement. Biochemical markers of bone remodeling can also be used to guide
      decision making regarding the treatment of metastatic bone disease and to
      determine the effectiveness of therapy for patients with cancer to bone whose
      broad-based symptoms make it difficult to discern true response to therapy.

PMID- 10898336
TI  - The role of positron emission tomography in the management of bone metastases.
AB  - BACKGROUND: Positron emission tomography (PET) is a nuclear medicine technique
      that only recently has been widely used in clinical oncology. PET, as a metabolic
      imaging technique, demonstrates advantages over and complements structural
      imaging methods and also demonstrates differences from conventional nuclear
      medicine, all of which has led to its enormous growth in clinical applications in
      recent years. METHODS: There is now a large body of literature on the use of PET
      with various tracers, especially (18)F-fluorodeoxyglucose ((18)FDG), in large
      numbers of patients with carcinoma. In the assessment of the skeleton in patients
      with carcinoma, early reports of PET imaging are now available with the use of
      (18)F-fluoride as a bone agent and the use of (18)FDG as a tumor agent, and the
      current knowledge is summarized in this report. RESULTS: High-quality tomographic
      PET bone scans are possible with (18)F-fluoride with possible advantages in
      sensitivity and specificity over conventional bone scintigraphy. With (18)FDG, it
      is possible to image tumor metabolism directly, and early studies have
      demonstrated a high sensitivity for the detection of skeletal metastases,
      although the demonstration of osteoblastic metastases may be less satisfactory.
      CONCLUSIONS: The clinical role of PET in the evaluation of patients with bone
      metastases is not yet defined; however, as described in this report, there is
      emerging evidence that this imaging method also may aid patient management in
      this area with the use of either (18)FDG or (18)F-fluoride ion.

PMID- 10898337
TI  - Samarium Sm-153 lexidronam for the palliation of bone pain associated with
      metastases.
AB  - BACKGROUND: In patients with bone pain due to metastatic disease, intravenous
      systemic radioisotope therapy may be a useful adjunct to other methods for
      palliating pain. METHODS: Various studies have been performed utilizing a short
      lived radioisotope conjugated to a tetraphosphonate (samarium 153 lexidronam)
      both as an open label and as a double blinded, placebo-controlled study. Patients
      with varying tumor types including those of the prostate, breast, lung, and other
      sites were studied. Two dose levels were used (0.5 millicuries (mCi)/kg and 1.0
      mCi/kg) with patients monitored for 16 weeks for efficacy (pain scores, opiod
      analgesic score, and quality of life) parameters and adverse events. RESULTS: All
      3 studies showed that at the 1.0 mCi/kg dose level statistically significant
      improvement over placebo was observed by 4 weeks with relief of pain noted in
      many patients by 1 week. The only significant adverse event was transient
      myelosuppression with a nadir at 4-6 weeks and recovery by 8 weeks. Less than 10%
      of patients had National Cancer Institute Common Toxicity Criteria Grade III/IV
      bone marrow toxicity recorded. CONCLUSIONS: Systemic metabolic radiotherapy with
      samarium 153 lexidronam appears to be a safe and efficacious method for treating
      patients with bone pain. The shorter radioisotope half-life allows for a high
      dose rate to be delivered over a short period, which may have certain biologic
      benefits.

PMID- 10898338
TI  - Complications of bone metastases: surgical management.
AB  - BACKGROUND: Patients with metastatic disease to the bone present a management
      challenge. Of the complications encountered in these patients, the predominant
      types that require surgical intervention are pathologic or impending fractures
      and neurologic compromise secondary to cord compression from spinal metastases. A
      multimodality approach is helpful in caring for these patients, and addressing
      complications related to bony metastatic disease with timely and appropriate
      intervention is an important step in optimizing care and quality of life.
      METHODS: This article incorporates information from multiple sources and presents
      recent reviews of the experience at the Memorial Sloan-Kettering Cancer Center
      with acetabular reconstruction for metastatic lesions, and with the use of the
      posterolateral transpedicular approach to address metastatic disease in the
      spine. RESULTS: Of 55 patients who underwent reconstruction of the acetabulum for
      metastatic disease, although there was a 25% incidence of local disease
      progression, there was only a 9% incidence of late fixation failure. Of the 41
      who were evaluable at 3 months, 83% continued to experience significant pain
      relief, and 50% of nonambulatory patients regained walking ability secondary to
      the procedure. Of the patients with more than 2 years of follow-up, 86%
      maintained pain relief and 71% maintained their ability to ambulate and function
      in their community. The preliminary series of 25 patients managed with a
      posterolateral transpedicular approach to address metastatic disease in the spine
      showed excellent tumor control, pain relief, and neurologic preservation with the
      technique. Particular benefit was obtained for patients with extensive epidural
      disease in which an anterior approach was contraindicated. CONCLUSIONS: Although
      a multimodality approach to the treatment of patients with metastatic disease to
      bone combining appropriate surgical intervention with systemic therapy and
      radiation can entail a major operative procedure, the overall benefits to a
      patient's quality of life outweigh the risks in most cases. Clinician awareness
      of the various therapeutic options and their indications, and aggressive advocacy
      of quality of life for these patients, can improve the care delivered to people
      with metastatic disease.

PMID- 10898339
TI  - Markers of bone turnover in bone metastases.
AB  - BACKGROUND: Bone metastases are a frequent complication of cancer disease. The
      evaluation of metastatic bone disease is crucial for the primary cancer staging
      because it will influence the therapeutic decision. The diagnosis of bone
      metastases usually relies on skeletal X-ray and bone scintigraphy. This latter
      technique is a sensitive diagnostic tool but lacks specificity. Moreover, the
      assessment of efficacy in the treatment of bone metastasis is difficult because
      the increased radionucleotide uptake does not always reflect an active metastatic
      area but may correspond to a bone reconstruction in patients responding to
      treatment. Markers of bone remodeling could help the clinician in the diagnosis
      and follow-up of bone metastases. METHODS: A common feature of both types of bone
      metastases (lytic or sclerotic) is an alteration of bone remodeling activity. The
      rate of formation or degradation of the bone matrix can be assessed either by
      measuring a prominent enzymatic activity of the bone forming or resorbing cells
      or by measuring bone matrix components released into the circulation during
      formation or resorption. They have been separated into markers of formation and
      resorption, but when both events are coupled and in balance, either of these
      markers will reflect the overall rate of bone turnover. These markers are of
      unequal specificity and sensitivity, and some of them have not been fully
      investigated yet in bone metastases. None of these markers is disease specific.
      RESULTS: Several studies of breast carcinoma showed increased levels of
      pyridinium cross-links in patients with bone metastases. However, in most
      studies, breast carcinoma patients without evidence of metastatic bone disease
      excreted pyridinium cross-links at a much higher rate than healthy controls.
      Similar findings have been observed with other types of primary cancer including
      lung, prostate, kidney, throat, and digestive carcinoma. Markers of bone
      formation had a low sensitivity in the diagnosis of bone metastasis, but they
      could be useful for prostate carcinoma, in which studies have shown that all
      patients without bone metastasis had normal value of bone alkaline phosphatase.
      Bone markers can be used for the follow-up of treatment, especially
      bisphosphonates therapy. Bisphosphonate infusion induces a large decrease of
      pyridinium cross-link level. Some studies suggest that a high level of resorption
      markers after treatment could reflect a resistance to the treatment. Moreover,
      some studies have shown that level of pyridinium cross-links before treatment
      could be a predictive factor of the response in multiple myeloma and prostate
      carcinoma. CONCLUSIONS: Bone markers have improved greatly in terms of
      sensitivity and specificity and could be useful for an early diagnosis of bone
      metastases. However, the clinical value of the use of bone markers in the
      diagnosis of bone metastasis has not been clearly shown yet with the possible
      exception of BPAL in prostate carcinoma. When bone is the only site of
      metastases, bone markers may be useful for monitoring patients with bone
      metastases. Markers of bone resorption are sensitive to changes in bone turnover
      induced by treatment. Bone resorption markers may be particularly useful for the
      follow-up of bisphosphonate treatment, which is increasingly used in the
      management of bone metastases.

PMID- 10898340
TI  - Cellular and molecular mechanisms of action of bisphosphonates.
AB  - BACKGROUND: Bisphosphonates currently are the most important class of
      antiresorptive agents used in the treatment of metabolic bone diseases, including
      tumor-associated osteolysis and hypercalcemia, Paget's disease, and osteoporosis.
      These compounds have high affinity for calcium and therefore target to bone
      mineral, where they appear to be internalized selectively by bone-resorbing
      osteoclasts and inhibit osteoclast function. METHODS: This article reviews the
      pharmacology of bisphosphonates and the relation between the chemical structure
      of bisphosphonates and antiresorptive potency, and describes recent new
      discoveries of their molecular mechanisms of action in osteoclasts. RESULTS:
      Bisphosphonates can be grouped into two pharmacologic classes with distinct
      molecular mechanisms of action. Nitrogen-containing bisphosphonates (the most
      potent class) act by inhibiting the mevalonate pathway in osteoclasts, thereby
      preventing prenylation of small GTPase signaling proteins required for osteoclast
      function. Bisphosphonates that lack a nitrogen in the chemical structure do not
      inhibit protein prenylation and have a different mode of action that may involve
      the formation of cytotoxic metabolites in osteoclasts or inhibition of protein
      tyrosine phosphatases. CONCLUSIONS: Bisphosphonates are highly effective
      inhibitors of bone resorption that selectively affect osteoclasts. After more
      than 30 years of clinical use, their molecular mechanisms of action are only just
      becoming clear.

PMID- 10898341
TI  - Actions of bisphosphonate on bone metastasis in animal models of breast
      carcinoma.
AB  - BACKGROUND: Bone, which abundantly stores a variety of growth factors, provides a
      fertile soil for cancer cells to develop metastases by supplying these growth
      factors as a consequence of osteoclastic bone resorption. Accordingly,
      suppression of osteoclast activity is a primary approach to inhibit bone
      metastasis, and bisphosphonate (BP), a specific inhibitor of osteoclasts, has
      been widely used for the treatment of bone metastases in cancer patients. To
      obtain further insights into the therapeutic usefulness of BP, the authors
      studied the effects of BP on bone and visceral metastases in animal models of
      metastasis. METHODS: The authors used two animal models of breast carcinoma
      metastasis that they had developed in their laboratory over the last several
      years. One model uses female young nude mice in which inoculation of the MDA-MB
      231 or MCF-7 human breast carcinoma cells into the left cardiac ventricle
      selectively develops osteolytic or osteosclerotic bone metastases, respectively.
      Another model uses syngeneic female mice (Balb/c) in which orthotopic inoculation
      of the 4T1 murine mammary carcinoma cells develops metastases in bone and
      visceral organs including lung, liver, and kidney. RESULTS: BP inhibited the
      development and progression of osteolytic bone metastases of MDA-MB-231 breast
      carcinoma through increased apoptosis in osteoclasts and breast carcinoma cells
      colonized in bone. In a preventative administration, however, BP alone increased
      the metastases to visceral organs with profound inhibition of bone metastases.
      However, combination of BP with anticancer agents such as uracil and tegafur or
      doxorubicin suppressed the metastases not only in bone but also visceral organs
      and prolonged the survival in 4T1 mammary tumor-bearing animals. Of interest,
      inhibition of early osteolysis by BP inhibited the subsequent development of
      osteosclerotic bone metastases of MCF-7 breast carcinoma. CONCLUSIONS: These
      results suggest that BP has beneficial effects on bone metastasis of breast
      carcinoma and is more effective when combined with anticancer agents. They also
      suggest that the animal models of bone metastasis described here allow us to
      design optimized regimen of BP administration for the treatment of breast
      carcinoma patients with bone and visceral metastases.

PMID- 10898342
TI  - The natural history, skeletal complications, and management of bone metastases in
      patients with prostate carcinoma.
AB  - BACKGROUND: Prostate carcinoma poses a significant public health problem.
      Although a minority of men with newly diagnosed prostate carcinoma manifest bone
      metastases or skeletal abnormalities, a significant proportion of men will
      develop these complications over the course of their lives. Patients at highest
      risk for bone metastases include those with high grade, high stage neoplasms,
      those who fail primary curative therapies such as radical prostatectomy or
      radiation therapy, and those who develop biochemical recurrence after hormonal
      therapy. METHODS: The relative risks and prognostic factors for bone metastases
      in each of these settings will be reviewed. RESULTS: In comparison with men
      without prostate carcinoma, benign skeletal complications (osteopenia and
      fractures) occur at significantly increased rates among men with untreated
      prostate carcinoma. Moreover, the incidence rate of these conditions increases
      dramatically among those men who are receiving endocrine therapy. The duration
      and intensity of the endocrine therapy may be associated with the incidence rate
      and severity of skeletal complications. CONCLUSIONS: Given the significant
      incidence rate and quality of life implications of skeletal complications and
      bone metastases, there is an urgent need to identify effective preventive
      therapies and treatments. Bisphosphonates may have a role in preventing
      osteopenia and, potentially, bone metastases among men with prostate carcinoma.

PMID- 10898343
TI  - Establishment of human prostate carcinoma skeletal metastasis models.
AB  - BACKGROUND: Prostate carcinoma progression from an androgen dependent (AD) state
      to an androgen independent (AI) state occurs clinically in patients who undergo
      hormonal therapy. In their laboratory, the authors developed two human prostate
      carcinoma skeletal metastasis models, the LNCaP progression model and the ARCaP
      model, to investigate phenotypic and genotypic changes of prostate carcinoma
      cells during disease progression and to understand molecular pathways for
      potential therapeutic targeting. METHODS: LNCaP or ARCaP cells were inoculated in
      athymic mice and were exposed to selective hormonal conditions both in vivo and
      in vitro. The effects of various hormonal treatment regimens on tumor volumes and
      distant metastasis and the effects of bone stromal cells on prostate specific
      antigen (PSA) expression by prostate carcinoma cells were evaluated. RESULTS: The
      authors propose that prostate carcinoma progression from the AD state to the AI
      state assumes three AI phenotypes: AI that remains androgen responsive, AI that
      is unresponsive to androgen stimulation, and AI that is suppressed by or
      hypersensitive to androgen. AI prostate carcinoma cells interacted reciprocally
      with osteoblasts to produce enhanced tumor growth and osteoblastic reaction when
      they are deposited in bone. Bone stromal cell conditioned media stimulated
      prostate carcinoma cell growth and suppressed its PSA expression, as also
      evidenced by androgen receptor-mediated transactivation of PSA promoter reporter
      activity. Conditioned media obtained from prostate carcinoma cells also
      stimulated osteoblastic cell growth in vitro. A novel gene therapy strategy is
      being developed to target prostatic tumor epithelium and its supporting stroma
      using tissue specific and tumor-restricted, promoter-directed toxic gene
      expression in both cellular compartments. In addition, new strategies are being
      designed to target the tumor endothelial system in the stroma and tumor cell
      extracellular matrix interaction mediated by isotype specific integrins.
      CONCLUSIONS: Prostate carcinoma skeletal metastasis models may prove useful in
      developing a new targeting strategy for the prevention and treatment of patients
      with prostate carcinoma.

PMID- 10898344
TI  - Prostate carcinoma: production of bioactive factors.
AB  - BACKGROUND: Many molecular mechanisms regulate prostate carcinoma pathogenesis,
      proliferation, and progression to bone metastases. The basic molecular mechanisms
      are endocrine, paracrine, autocrine, and intracrine. These mechanisms can be
      mediated by a variety of agents, including gonadal and adrenal steroids, retinoic
      acid and vitamin D derivatives, neuroendocrine factors, growth factors,
      cytokines, lymphokine, and bone factors. Prominent among them is parathyroid
      hormone-related protein (PTHrP). METHODS: The author studied the expression and
      regulation of PTHrP production in prostate carcinoma cells with nucleic acid and
      immunochemical probes for the polypeptide. The robust expression of this
      oncoprotein by prostate carcinoma has been demonstrated. In the current study the
      author reviews his results and the studies of other investigators regarding PTHrP
      and the variety of bioactive factors produced by prostate cells. RESULTS: PTHrP
      is expressed by most prostate carcinoma. It also is expressed by normal and
      hyperplastic prostate cells, and there is a gradient of expression that peaks in
      malignant prostate cells. PTHrP is processed by carcinoma cells into peptides
      that have unique biologic effects. Among them are regulation of growth and
      cytokine expression. It has been observed that the effect of PTHrP can be
      mediated by novel intracrine pathways in prostate carcinoma. These mechanisms
      influence transduction of growth regulatory signaling pathways, cell
      proliferation, immunoregulation, and angiogenesis. CONCLUSIONS: The current study
      identified PTHrP among the bioactive prostate factors that appear to participate
      in prostate carcinoma pathogenesis and progression. This oncofetal protein is
      commonly expressed by prostate carcinoma, and its regulatory interactions with
      other bioactive prostate cell products play an important role in the pathobiology
      of prostate carcinoma. Understanding these regulatory interactions among prostate
      carcinoma, its cell products, and the skeleton continues to provide insights into
      the pathogenesis of this disease entity and may provide clues to clinical
      management.

PMID- 10898345
TI  - Hormone therapy for patients with prostate carcinoma.
AB  - BACKGROUND: Androgen ablation as a treatment for patients with prostate carcinoma
      was described 60 years ago. Despite the long pedigree for this treatment, the
      optimal use of androgen ablation therapy remains extremely controversial.
      Monitoring the level of prostate specific antigen (PSA) has created a dramatic
      shift in the population of patients in whom androgen ablation is initiated. This
      has resulted in a number of changing concepts of treatment. Patients with
      recurrent prostate carcinoma after the failure of local therapy are now diagnosed
      with recurrent disease on the basis of a rising PSA level. These patients have a
      median life expectancy of 10-15 years compared with 3 years for patients who
      present with metastatic disease. This means that the systemic side effects of
      androgen ablation and the impact on quality of life have become more important.
      Controversies exist with respect to the timing of therapy, the use of
      intermittent androgen ablation, and the role of total androgen blockade. METHODS:
      A critical review of the literature, with an emphasis on quality of life and
      recent publications, was performed. RESULTS: Data support the early initiation of
      androgen ablation for patients with locally advanced or lymph node positive
      prostate carcinoma. There are no data supporting a particular PSA trigger point
      or a PSA doubling time for the initiation of androgen ablation therapy after the
      failure of local radical therapy. The combined results of 27 prospective
      randomized trials of total androgen blockade support the finding of a modest
      survival benefit for patients who undergo androgen ablation with combined
      therapy. The average, absolute 5-year survival rate was improved by 3% (a 10%
      reduction in the risk of dying), with a 95% confidence interval between 0.4% and
      6.0%. Intermittent therapy resulted in an improved quality of life in the off
      treatment interval. Uncertainty remains with respect to the long term effect of
      intermittent androgen ablation therapy on patient survival. This is being studied
      in a prospective intergroup trial comparing continuous therapy with intermittent
      therapy carried out by the National Cancer Institute Criteria/Canadian Uro
      Oncology Group and the Southwest Oncology Group. CONCLUSIONS: Androgen ablation
      therapy is an effective treatment for patients with advanced prostate carcinoma.
      It has serious limitations, however. Although it improves patient survival, it is
      not curative, and it is associated with a substantial adverse impact on the
      quality of life for patients, particularly when its use is prolonged. The advent
      of intermittent therapy may reduce this impact. The real challenge, however, is
      to develop better means to avert hormone-refractory prostate carcinoma and better
      treatments for patients with hormone-refractory disease when it occurs.

PMID- 10898346
TI  - Chemotherapy for patients with advanced prostate carcinoma: a new option for
      therapy.
AB  - BACKGROUND: Prostate carcinoma is the second leading cause of cancer-related
      death in men in the United States. In nearly all of these men, cancer progressed
      despite initial treatment with androgen ablation therapy. Managing hormone
      refractory prostate carcinoma remains a difficult challenge for the clinician. In
      the past, cytotoxic chemotherapy was considered inactive, but recent advances
      have altered this view significantly. METHODS: A MEDLINE review of recent studies
      of chemotherapy in hormone-refractory prostate carcinoma was performed. RESULTS:
      Benefit of treatment may now be measured by prostate specific antigen as a marker
      of antitumor activity, quality of life and pain scores, and traditional objective
      measures of response. The antiandrogen withdrawal syndrome and secondary hormonal
      therapies are important treatment options that usually precede chemotherapy. New
      drug combinations are demonstrating promising levels of efficacy and proven
      palliative ability. Two large randomized trials have shown that mitoxantrone in
      combination with steroids is more effective in improving pain and quality of life
      than steroids alone. In several Phase II studies, estramustine combinations with
      vinblastine, etoposide, paclitaxel, or docetaxel produced significant responses
      in over 50% of patients. Future research will define optimal chemotherapy
      combinations and test new agents. In addition, systemic chemotherapy is being
      investigated in earlier stages of prostate carcinoma at high risk for
      progression. CONCLUSIONS: Cytotoxic chemotherapy has demonstrated clear activity
      and palliative benefit in patients with hormone-refractory prostate carcinoma.
      Its role in managing advanced prostate carcinoma patients is growing but remains
      an area of active investigation.

PMID- 10898347
TI  - Bisphosphonates in multiple myeloma.
AB  - BACKGROUND: Myelomatosis is associated with considerable skeletal morbidity,
      particularly bone pain and fractures. Hypercalcaemia is a common presenting
      feature but less common after adequate chemotherapy. These complications are
      caused by progressive focal and generalized osteolysis due, in turn, to increased
      activation of osteoclasts by osteoclast activating factors. These include tumor
      necrosis factor-beta, interleukin-1, and interleukin-6. The knowledge that
      disturbed bone remodeling is due to the activation of authentic osteoclasts
      provides the rationale for the use of bisphosphonates in myelomatosis. METHODS:
      This article reviews the place of bisphosphonates in the management of myeloma.
      RESULTS: There is good evidence that hypercalcaemia can be corrected with
      intravenous or oral bisphosphonates, and they are now the specific treatment of
      choice. Several studies have shown that their intravenous administration is
      beneficial in the acute management of bone pain due to malignancy, but studies in
      myelomatosis are lacking. In contrast, a number of well designed controlled
      studies have shown significant effects of long term treatment with clodronate and
      pamidronate to decrease the incidence of skeletal complications in myelomatosis.
      Benefits reported are a decreased incidence of bone pain, hypercalcaemia,
      vertebral and long-bone fractures, and the extension of osteolytic lesions. There
      may be a beneficial effect on survival, but this is much less certain.
      CONCLUSIONS: These agents provide a valuable adjunct to the management of
      myelomatosis.

PMID- 10898348
TI  - Bisphosphonates and breast carcinoma: present and future.
AB  - BACKGROUND: Bisphosphonates are analogues of endogenous pyrophosphates in which a
      carbon atom replaces the central atom of oxygen. Bisphosphonates are potent
      inhibitors of osteoclastic bone resorption and are effective in decreasing the
      incidence of skeletal complications in breast carcinoma patients with osteolytic
      bone metastases. METHODS: Zoledronate is a new, potent third-generation
      bisphosphonate that is 500-1000 times more potent than pamidronate. A Phase II
      clinical trial of 0.4, 2.0, or 4.0 mg of zoledronate as a 5-minute infusion or 90
      mg of pamidronate as a 2-hour infusion recently was completed. In addition,
      osteoprotegerin (OPG) recently has been identified as a novel, naturally
      occurring protein that inhibits osteoclast formation. RESULTS: A 5-minute
      infusion of 2.0 or 4.0 mg of zoledronate is at least as effective as 90 mg of
      pamidronate in preventing skeletal complications. OPG currently is entering Phase
      I clinical trials. Finally, tumor cells staining strongly for matrix
      metalloproteinases are observed in osteolytic pathologic bone fractures secondary
      to metastatic carcinoma. In many of these lesions frequent tumor cells are
      observed and osteoclasts are rare. CONCLUSIONS: Bisphosphonate treatment can
      decrease skeletal events in patients with breast carcinoma that is metastatic to
      bone. Current trials to improve results further are employing more potent
      bisphosphonates such as zoledronate and nonbisphosphate inhibitors of osteoclasts
      such as OPG. An osteoclast-independent phase of bone destruction also deserves
      further consideration.

PMID- 10898349
TI  - The potential role of bisphosphonates as adjuvant therapy in the prevention of
      bone metastases.
AB  - BACKGROUND: Bisphosphonates (BPs) reduce bone resorption rates by inhibiting
      osteoclast function, although direct antineoplastic effects and poorly understood
      effects on bone pain also may occur. Within the family of BPs there are more
      similarities in pharmacologic effects than differences, although side effect
      profiles, rates of oral absorption, and potency do differ. Oral clodronate and
      intravenous pamidronate reduce skeletal complications in patients with bone
      metastases from breast carcinoma (as well as in myeloma). Uncontrolled trials of
      prostate carcinoma also suggest clinical benefit. METHODS: Animal studies show
      that BPs can reduce the rate of development of bone metastases (for example, in
      Walker 256 carcinoma), but there is little evidence of an effect at nonosseous
      sites. The hypothesis that the growth of subclinical osseous metastases is
      augmented by products of bone resorption (a "vicious cycle") and may be
      diminished by a local reduction of these substances has led to trials of BPs
      involving patients with no clinical evidence of bone metastases. These trials are
      critically assessed in this review. RESULTS: In patients with recurrent breast
      carcinoma but no overt bone metastases, oral clodronate reduced the number of
      diagnosed bone metastases; but the number of patients who had relapses in bone,
      though smaller, was not significantly different from the number among patients
      who took placebo. In a trial of oral pamidronate, no effect was seen, but
      compliance was a problem because of gastrointestinal side effects. Patients
      treated for operable breast carcinoma have four or five times the normal rate of
      vertebral fracture, and BPs do reduce the rate of bone loss. Three adjuvant
      clodronate trials have been reported. The first, an open-label controlled trial
      (Diel et al.), showed a reduction in osseous and nonosseous recurrences and an
      increase in disease free and overall survival with 2 years of clodronate. A
      second open-label trial (Saarto et al.) of similar size involving lymph node
      positive breast carcinoma patients showed no effect on the rate of bone
      metastasis relapse and a deleterious effect on relapse rates of nonosseous
      metastases with 3 years of clodronate. A third placebo-controlled trial involving
      1079 patients reported, in an interim analysis, a reduction in osseous metastases
      during treatment with 2 years of clodronate, but no effect on nonosseous
      metastases or survival. CONCLUSIONS: A confirmatory clinical trial is required
      for two interrelated reasons: 1) scientifically, it is important to demonstrate
      that an agent that has its dominant effect on a normal tissue cell, the
      osteoclast, can influence the growth of neoplastic cells; and 2) from the
      perspective of patient care, it must be unequivocally shown that a reduction in
      the rate of osseous recurrence translates into an improvement in disease free
      survival or an improvement in quality of life through reduction of adverse
      skeletal events. The National Surgical Adjuvant Breast Project has committed to
      conducting this study and including women with operable breast carcinoma.

PMID- 10898350
TI  - Bisphosphonates in the management of prostate carcinoma metastatic to the
      skeleton.
AB  - BACKGROUND: Prostate carcinoma metastasizes frequently to the skeleton, causing
      significant morbidity, particularly severe bone pain. Metastatic lesions
      typically are osteosclerotic, but there is experimental, histologic, and
      biochemical evidence of increased bone resorption. Furthermore, bone resorption
      rates appear to correlate with bone pain. These observations provide the
      rationale for the use of bisphosphonates in the management of patients with
      prostate carcinoma and skeletal metastases. METHODS: The authors reviewed the
      literature and current findings on the use of biphosphonates in the management of
      patients with prostate carcinoma metastatic to the skeleton. RESULTS: Compared
      with the large number of studies with bisphosphonates in predominantly osteolytic
      bone disease, there have been relatively few (mostly uncontrolled) studies in
      patients with prostate carcinoma. Apart from the lack of appropriate experimental
      models, the osteoblastic nature of the metastases and the low incidence of
      objectively assessed endpoints of treatment (e.g., hypercalcemia, pathologic
      fractures) have delayed developments. Available data, however, strongly suggest
      that potent bisphosphonates are efficacious in reducing skeletal morbidity in
      patients with prostate carcinoma. CONCLUSIONS: For the optimal management of
      patients with skeletal metastases from prostate carcinoma with bisphosphonates
      their mode of administration, the dose and duration of treatment need to be
      evaluated. Better understanding of the cellular and molecular mechanisms
      underlying bone metastases can lead to the design of improved treatment protocols
      with potent bisphosphonates.

PMID- 10898351
TI  - Current and future directions in medical therapy: hypercalcemia.
AB  - BACKGROUND: Tumor-induced hypercalcemia (TIH) is essentially due to a marked
      stimulation of osteoclast-mediated bone resorption. An inhibition of bone
      formation and an enhanced tubular reabsorption of calcium play an important
      contributory role. These factors explain why serum calcium often rises rapidly in
      cancer patients and why high doses of bisphosphonates are needed to normalize
      bone resorption and to overcome the contributory role of the kidney. METHODS: The
      author provides a short review of clinical trials in hypercalcemic cancer
      patients, with an emphasis on the most recent trials. RESULTS: Rehydration and
      bisphosphonates now constitute the standard treatment of TIH. A single-day 1500
      mg infusion of clodronate achieves normocalcemia in approximately 80% of the
      cases. Clodronate also can be given by subcutaneous infusion that can be
      particularly useful in the palliative setting. A dose of 90 mg of pamidronate
      achieves normocalcemia in more than 90% of the patients and has a longer-lasting
      effect than clodronate. Newer more potent bisphosphonates, such as ibandronate
      and zoledronate, may improve these results, and they certainly will simplify the
      therapeutic schemes. Ibandronate at the dose of 6 mg normalizes serum calcium in
      more than 75% of the patients with moderate or severe hypercalcemia. Of note, the
      same doses of pamidronate and ibandronate, repeated monthly for 1-2 years, have
      been shown to substantially reduce the skeletal morbidity rate in normocalcemic
      patients with tumor bone disease. Even lower doses of zoledronate, the most
      potent bisphosphonate tested so far, are able to correct TIH when administered as
      a 30-minute infusion. CONCLUSIONS: Bisphosphonates have become the standard
      treatment for cancer hypercalcemia. Success is achieved in more than 90% of the
      cases. Other classes of compounds are being tested for their antiosteoclastic
      activity, and animal studies suggest that osteoprotegerin could be as efficient
      and act faster than bisphosphonates.

PMID- 10898352
TI  - High dose chemotherapy: rationale and results in breast carcinoma.
AB  - BACKGROUND: High dose chemotherapy (HDC) with hematopoietic stem cell support is
      an increasingly important strategy in the management of advanced cancer. Early
      Phase II studies and the development of peripheral blood stem cell support to
      enable safe and tolerable myeloablative chemotherapy has resulted in its
      controversial and widespread use in the management of breast carcinoma. Recently,
      several randomized trials of both advanced breast carcinoma and the adjuvant
      setting have been reported. METHODS: The technical developments in HDC and
      results from the randomized clinical trials reported to date were reviewed.
      RESULTS: Three randomized trials of advanced breast carcinoma and five of high
      risk adjuvant patients were identified. Only two relatively small trials from
      South Africa have so far shown an advantage for high dose chemotherapy, and the
      validity of these trials has recently been seriously challenged. A Scandinavian
      adjuvant trial showed no advantage for HDC when compared with maximum nonablative
      doses supported with granulocyte-colony stimulating factor (G-CSF). Four trials
      were too small to detect clinically realistic differences in outcome, whereas the
      other large adjuvant trial was reported prematurely and the results in the HDC
      arm were dominated by high procedure-related mortality. CONCLUSIONS: It is
      difficult to make specific treatment recommendations based on the conclusions
      from the currently available data. The 1999 American Society of Clinical Oncology
      reports were inconsistent and in some cases were presented before the results
      were sufficiently mature to provide statistically reliable data. However, it is
      clear that, unlike in leukemia, lymphoma, and multiple myeloma, HDC in breast
      carcinoma should not be used outside the context of a clinical trial. The mature
      results of the ongoing trials are eagerly awaited, whereas the use of immediate
      as opposed to consolidation high dose treatment, tandem transplants, and
      developments in immunologic and genetic manipulation of the graft merit further
      evaluation.

PMID- 10898353
TI  - Current and future directions in medical therapy for breast carcinoma: endocrine
      treatment.
AB  - Endocrine therapy remains a mainstay of treatment for breast carcinoma in both
      adjuvant and metastatic settings. The choice of endocrine therapy is guided by
      the presence and degree of expression of estrogen receptor (ER) and progesterone
      receptor (PgR) as well as by clinical parameters. Adjuvant tamoxifen (TAM) given
      for 5 years is accepted standard therapy for postmenopausal ER and/or PgR
      positive (+ve) women. In premenopausal women, 5 years of TAM given alone has
      similar effects, but is used less frequently because chemotherapy has been
      regarded as a standard even in ER and PgR +ve women. Recent literature has
      demonstrated the equivalence or superiority of (Zoladex [ZOL], Zeneca
      Pharmaceuticals, Wilmington, DE) goserelin acetate plus TAM to cyclophosphamide,
      methotrexate, and 5-fluorouracil (CMF) chemotherapy in premenopausal ER and PgR
      +ve women. This, together with older data showing equivalence or superiority of
      ovarian ablation (OA) to CMF chemotherapy in the same setting, as well as
      accumulating data suggesting benefit from the addition of ZOL, OA, and/or TAM to
      chemotherapy in the premenopausal adjuvant setting, has raised issues regarding
      whether ZOL, OA, and/or TAM can substitute for chemotherapy or should always be
      added to it for premenopausal receptor +ve women. In the metastatic setting, the
      second-generation aromatase inhibitors (AI) clearly have moved into position as
      second-line therapy after TAM. Recent data have shown equivalence and perhaps
      some superiority to TAM by at least one AI (anastrazole [AN]) in first-line
      metastatic treatment. The results of adjuvant studies comparing TAM, AN, and TAM
      + AN in the adjuvant setting will be awaited with great interest. In the interim,
      the development of other SERMS (raloxifene, EM 850) and of pure antiestrogens may
      provide new and exciting approaches in the metastatic, adjuvant, and preventive
      settings.

PMID- 10898354
TI  - Developments in chemotherapy of breast cancer.
AB  - BACKGROUND: Breast carcinoma is moderately sensitive to multiple antitumor
      agents. Cytotoxic combination regimens developed in the 1970s were shown to
      produce higher response rates and longer durations of response and survival than
      single-agent therapy. These regimens became the standard of care for the
      management of metastatic, hormone-refractory breast carcinoma, and more recently,
      for primary breast carcinoma. Randomized trials also have demonstrated that
      anthracycline-containing combinations were more effective than combinations
      without anthracyclines. The development of several new cytotoxic agents and novel
      antitumor strategies prompted this review. METHODS: The author conducted a
      computerized literature search of MEDLINE and CANCERLIT and also reviewed the
      abstracts of major oncology meetings (ASCO, American Association for Cancer
      Research, ESMO, and San Antonio Breast Cancer Symposium) over the past 10 years.
      RESULTS: Effective new cytotoxic drugs include the taxanes (paclitaxel and
      docetaxel), vinorelbine, gemcitabine, and capecitabine. The identification of
      specific molecular abnormalities (HER-2/neu or epidermal growth factor receptor
      [EGFR] overexpression) led to the development of targeted therapeutic
      intervention (monoclonal antibodies and tyrosine kinase inhibitors). Trastuzumab,
      a monoclonal antibody against the HER-2/neu oncoprotein, produced objective
      regression in 15-20% of patients with HER-2/neu-overexpressing breast carcinoma
      and improved the efficacy of paclitaxel. Other productive directions of
      therapeutic research include inhibition of intracellular signaling, interference
      with tumor angiogenesis, cell cycle regulation, and the development of vaccines.
      CONCLUSIONS: Expanded understanding of the biology of breast carcinoma led to the
      development of rational therapeutic interventions, many of which are currently
      under active clinical development.

PMID- 10898355
TI  - Bisphosphonates and the prevention of metastasis: first evidences from
      preclinical and clinical studies.
AB  - BACKGROUND: Bisphosphonates have been used successfully for many years in the
      treatment of hypercalcemia and to reduce skeletal-related complications of
      metastases. In the first years of bisphosphonate use, the efficacy of these
      substances was thought to lie purely in the inhibition of osteoclasts. However,
      there is recent evidence to suggest that an antitumor effect also may play a
      role. As well as having an apoptotic and antiproliferative effect on osteoclasts,
      bisphosphonates may exert a similar influence on macrophages and tumor cells.
      METHODS: The current investigation summarizes all results published to date that
      deal with the potential antitumor properties of the bisphosphonates. On the one
      hand, these include results from basic research into the action mechanism and
      preventative models in animals. In addition, the results of initial clinical
      experience with metastasis prophylaxis with bisphosphonates in breast carcinoma
      patients are presented and interpreted. RESULTS: Improvements in the survival
      time of certain subpopulations have been found in many Phase III studies with
      bisphosphonates to date, both in the setting of metastatic breast carcinoma and
      in multiple myeloma. Some preclinical studies showed that down-regulation of bone
      metabolism by bisphosphonates is associated with a lower incidence of bone
      metastases and destruction in animals, whereas activation is correlated with a
      higher number of metastases. However, varying results were found in animal
      experiments with regard to the effect of bisphosphonates on the incidence and
      growth pattern of nonosseous metastases. The results of three randomized studies
      in patients with primary breast carcinoma in which patients received 1600 mg
      clodronate orally have now been evaluated and presented. All three studies
      arrived at different results. Because the dose was identical in all three
      studies, the differing results can only be either random or methodologic
      (inclusion criteria, sample size, etc.). CONCLUSIONS: Overall, the results are
      very promising but need confirmation in further studies. At the moment, we have
      more open than answered questions. First, it is unclear whether this type of
      adjuvant therapy with bisphosphonates should be given continually by the oral
      route, or whether an intravenous interval therapy could produce the same results.
      It is also uncertain whether the doses used in a palliative setting are optimal
      or whether lower doses might also suffice. The optimum period of adjuvant
      treatment is also subject to debate. What is clear, however, is that confirmation
      of the initial clinical results will open a new chapter in the treatment of
      malignant tumors.

PMID- 10898356
TI  - Biology of meningiomas.

PMID- 10898357
TI  - Growth of incidental meningiomas.
AB  - The aim of this study was to assess the growth of incidental meningiomas, to
      establish a strategy for dealing with these tumours. The cases of 37 patients
      with a meningioma revealed incidentally by computerized tomography or magnetic
      resonance imaging, who were followed at least once by an additional imaging
      study, were reviewed. The tumour volume was calculated, to estimate the annual
      growth rate of the incidental meningiomas. Nine of the 37 patients (24.3%) showed
      a considerable increase (the annual growth rate > 1 cu cm/year) in their tumour
      volume (tumour growth). There was no significant difference in the follow-up
      period, age, or the volume of tumour between the patients with and without tumour
      growth. However, a multivariate analysis revealed that the likelihood of tumour
      growth independently and significantly increased according to a decrease in the
      age of the patients (Odds ratio 0.18 for one-standard-deviation change (ISD) 12.6
      years, p = 0.042) and according to an increase in the volume of the tumour (Odds
      ratio 3.64 for ISD 4.46 cu cm, p = 0.042). The majority of patients with
      incidental meningioma can be apparently observed without any surgical
      intervention, because their annual growth rates are generally less than 1 cu
      cm/year. However, clinical and radiological observations would be advisable for
      these patients (especially young patients and patients with a large tumour), in
      view of the presence of rapidly growing tumours in some of the patients.

PMID- 10898358
TI  - Tentorial meningiomas. Report on twenty-seven cases.
AB  - OBJECTIVE: Report our experience with 27 tentorial meningiomas (TM) surgically
      treated between 1985 and 1998. METHODS: The records of 27 patients with TMs were
      retrospectively reviewed for clinical presentation, neuroradiological evaluation,
      surgical treatment and long-term outcome. The extent of tumor resection was
      scored according to the Simpson's grading for tumor removal. Long-term results
      were evaluated according to the Glasgow Outcome Score (GOS). RESULTS: The average
      age was 53 years. Female predominance was 74%. The most common complaints at
      presentation were headaches (51%), gait ataxia (33%), memory disturbances (30%)
      and hypoacousia (30%). A classification of TMs into 5 subgroups according to
      tumor site is proposed on the basis of imaging studies. A cerebrospinal fluid
      shunt was established prior to direct approach in 7 patients and as the sole
      procedure in one inoperable patient. Twenty-seven direct approaches were
      undertaken in 26 patients, including 17 infratentorial and 10 supratentorial
      approaches. Total tumor removal was achieved in 20 patients (77%) and subtotal
      removal in 6 (23%). Fifteen patients (55%) experienced 22 postoperative
      complications. One patient died three months after a subtotal resection
      (mortality = 3.7%). With a mean follow-up of 54 months, all 26 survivors are
      currently alive with 23 having resumed their normal activities and 3 needing
      assistance. Five of 6 patients with subtotal resection survived and were followed
      for a period ranging from 72 to 132 months: none showed residual tumor
      progression and no re-operation was considered. An additional patient experienced
      a (<true>) recurrence 6 years after total removal, with no tumor progression 2
      years after his recurrence was recognized. DISCUSSION: The best surgical approach
      to TMs is still a controversial matter. The advantages and drawbacks of
      conventional versus transbasal approaches are reviewed. Our experience suggests
      that subtotal removal can be associated with long recurrence-free intervals and
      preserved quality of life. TMs located at the tentorial edge carried a definitely
      worse prognosis than peripheral forms.

PMID- 10898359
TI  - Gamma surgery for hemangiopericytomas.
AB  - A retrospective analysis of a consecutive series of 12 patients with 15
      intracranial hemangiopericytomas treated at the University of Virginia using
      Gamma surgery is presented. Clinical and radiographic follow up of 3 to 56 months
      is available for 10 patients with 12 tumors. There was one tumor present at the
      time of initial Gamma surgery in each patient. Two new tumors occurred in
      patients previously treated. Nine of the tumors decreased in volume and three
      remained stable. Four of the nine tumors that shrank later progressed at an
      average of 22 months after treatment. Of the tumors that decreased in volume and
      have not progressed, the response has been for an average of 11 months. The
      follow-up for two tumors that remained unchanged was 10 and 34 months (average 22
      months). A third tumor was unchanged at 42 months but the patient died of new
      disease adjacent to the treated area in the anterior skull base. There were no
      complications and the quality of life following the procedure was maintained or
      improved in every case. Gamma surgery is effective in palliating the patients by
      decreasing tumor volume and delaying recurrence.

PMID- 10898360
TI  - Complete removal of colloid cyst via CT-guided stereotactic biportal
      neuroendoscopy.
AB  - Four patients harbouring a colloid cyst of the 3rd ventricle were operated on
      endoscopically. With the "classical" monoportal technique, through a precoronal
      burr hole only partial removal could be achieved in the first case. As the
      crucial point of the procedure is the safe dissection of the cyst from the thela
      chorioidea and from the internal cerebral veins, adequate control of the
      posterior rim of the foramen of Monro and the roof of the 3rd ventricle is
      mandatory. Accordingly in other three cases a CT-guided biportal endoscopic
      technique was applied, which permitted radical removal of the entire cyst with
      maximum safety. CT-guidance is essential for optimal planning after careful study
      of the individual anatomy. In this way the rigid scopes are moved exclusively
      along their own axes throughout the procedure, the resulting brain damage thereby
      being minimal. With regard to all circumstances of the procedure, the use of
      flexible endoscopes appears to be inappropriate and biportal endoscopy offers
      itself as the method of choice.

PMID- 10898361
TI  - Intramedullary spinal cord ganglioglioma: a report of five cases.
AB  - We report five cases of ganglioglioma in various locations. The tumours were
      removed with gross total resection in most cases without any further neurological
      deterioration. Without any additional treatment, no evidence of recurrence or
      regrowth of tumours was observed in the mean follow-up period of 4.1 years. We
      suggest that intramedullary spinal cord gangliogliomas be resected totally due to
      the high risk of recurrence and regrowth rate of the tumours with subtotal
      resection in the long term considering especially that these tumours affect
      predominantly young patients.

PMID- 10898362
TI  - MRI-findings after uncomplicated anterior cervical discectomy.
AB  - BACKGROUND: The anterior approach for cervical discectomy with methacrylate
      implant involves manipulations on vertebral bodies and ligaments. Foreign
      materials like methacrylate and fibrin sponge are inserted. On postoperative MRI
      it may be difficult to differentiate pathological from "normal" findings caused
      by routine manipulations. METHOD: In this study 14 patients free of symptoms
      after anterior discectomy with methacrylate-implant were examined clinically and
      a MRI was performed on the 7th day after surgery and again after a 6 month follow
      up. All patients had an uneventful recovery and no signs of inflammation after
      surgery. FINDINGS: Independent of the underlying pathology (e.g. soft or hard
      disc) 73% of the patients had a signal reduction within the vertebral bodies
      adjacent to the operated disc on T1-weighted spin-echo images on the 7th
      postoperative day. Signal intensities were normal after 6 months in all patients.
      Remarkable metal artifacts were present in one patient only. The methacrylate
      implant could be identified as a hypo-intense structure on all sequences at any
      time without artifacts. In 80% of the cases a hyperintensity was found on T2
      weighted images between the methacrylate-implant and the dura on the 7th
      postoperative day. A protrusion of the posterior ligament was present at the
      level of the operated disc on day 7 after surgery, which had resolved completely
      6 months later. This may mimic residual disc tissue or osteophytes early after
      surgery. INTERPRETATION: It is very important to know this "normal" postoperative
      appearance of the cervical spine in order to avoid misinterpretations.

PMID- 10898363
TI  - Recurrent trigeminal neuralgia after microvascular decompression using an
      interposing technique. Teflon felt adhesion and the sling retraction technique.
AB  - The causes of recurrence after microvascular decompression for trigeminal
      neuralgia and the results of re-operations were studied in 6 cases. Eighty-two
      patients with trigeminal neuralgia were operated on through microvascular
      decompression using the technique of interposing Teflon felt between the
      offending artery and the pons and/or nerve. Recurrence occurred in 14 cases
      (17.1%) and re-operations were carried out in 6 severe cases at which time the
      sling retraction technique was used. At the second operation, the adhesion of the
      interposed Teflon felt was found at the trigeminal nerve in all cases and the
      adhesions were the main cause of recurrence. The Teflon felt was dissected from
      the nerve, and the sling of the Teflon felt adhering to the offending arteries
      was fixed to the tentorium in order to transpose the arteries and avoid re
      adhesion. All cases resulted in an excellent relief from pain and experienced no
      pain for at least 2 years. The intra-operative findings of our cases indicated
      that the microvascular decompression using the interposing technique may result
      in adhesion of the prosthesis to the nerve and thus eventually lead to
      recurrence. Our surgical experience also suggests that such recurrent cases
      should be re-operated on using the sling retraction technique instead of the
      interposing technique, even for the first microvascular decompression procedure.

PMID- 10898364
TI  - Accurate placement of the distal end of a ventriculoatrial shunt catheter using
      Alphacard: direct intraoperative comparison with fluoroscopy.
AB  - BACKGROUND: Surgical insertion of a ventriculoatrial shunt requires accurate
      placement of the atrial catheter in the right atrium in order to prevent
      postoperative complications. Fluoroscopy is the standard method for monitoring
      correct positioning of the catheter. METHODS: This paper reports a prospective
      study in 50 patients with the aim of comparing electrocardiographic monitoring of
      the catheter position by means of Alphacard with concomitant intraoperative
      fluoroscopic examination. The Alphacard was evaluated in terms of accuracy, time
      requirement, and ease of handling. The mean postoperative follow-up period was 54
      (range 42-66) months. FINDINGS: Reliable control of the catheter position was
      possible by means of electrocardiographic guidance in all 50 patients (100%) by
      fluoroscopy in 49 cases (98%). The average time required for intra-operative
      monitoring of the catheter position was 55 (40-70) seconds for
      electrocardiography as compared to 8 (5-12) minutes for fluoroscopy. None of the
      patients showed obstruction of the atrial catheter during the postoperative
      follow-up period. INTERPRETATION: Alphacard offers an excellent alternative for
      monitoring the position of the tip of an atrial catheter because it requires
      little equipment and time. In terms of reliability, it is comparable or even
      superior to fluoroscopy.

PMID- 10898365
TI  - Motor function changes in the rat following severe spinal cord injury. Does
      treatment with moderate systemic hypothermia improve functional outcome?
AB  - Systemic hypothermia exerts neuroprotective effects following trauma and ischemia
      caused by vascular occlusion in the brain. In the spinal cord similar effects
      have been demonstrated following ischemia after aortic occlusion. We have
      previously presented protective effects on several morphological parameters in
      the early period after the injury, using an established spinal cord compression
      injury model and systemic hypothermia. In the present study we have evaluated the
      effects on motor function following severe spinal cord compression trauma and
      treatment with moderate systemic hypothermia. Thirty Sprague Dawley rats were
      randomized into three groups: In group 1 (n = 4), the animals underwent a
      hypothermic procedure, including a 2 h hypothermic period with a body temperature
      of 30 degrees C, following the initial laminectomy. In group 2 (n = 12) a 50 g
      compression was applied to the spinal cords for 5 min, after which the animals
      were kept under normothermic anesthesia for 3 h. In group 3 (n = 14), the animals
      underwent the same trauma procedure as in group 2 and the same hypothermic
      procedure as in group 1. The animals were allowed to survive for 14 days, during
      which the motor function was recorded. This degree of trauma results in a non
      reversible paraplegia, and the addition of systemic hypothermia as described
      above did not alter the neurological recovery as measured by two different
      methods of recording the motor function up to two weeks after injury. All animals
      survived in group 1. However, the mortality rates in group 2 were 25% and in
      group 3, 50%, respectively, which mirrors the severity of the trauma. The
      application of systemic hypothermia and the lack of experimental therapeutic
      success highlight the difficulties of transferring experimental beneficial
      neuroprotective effects to a clinically useful treatment method. In this
      experimental set-up the effects of the severe primary injury may overshadow the
      effects of the secondary injury mechanisms, which limits the therapeutic
      possibilities of systemic hypothermic treatment.

PMID- 10898366
TI  - Time-course of blood-brain barrier permeability changes after experimental
      subarachnoid haemorrhage.
AB  - An increase in blood-brain barrier (BBB) permeability after subarachnoid
      haemorrhage (SAH) has been described in humans and has been correlated with
      delayed cerebral ischemia and poor clinical outcome. Few studies examined in the
      laboratory the relationship between SAH and BBB, with contrasting results due to
      limitations in experimental probes adopted and in timing of observation. The aim
      of this study was to quantify the time-course of BBB changes after experimental
      SAH. Groups of eight rats received injections of 400 microl of autologous
      arterial blood into the cisterna magna. BBB was assessed 6, 12, 24, 36, 48, 60,
      and 72 hours after SAH and in sham-operated animals separately for cerebral
      cortex, i.e. frontal, temporal, parietal, occipital, subcortical gray matter
      (Caudate-Putamen-Thalamus), cerebellar cortex and nuclei, and brain stem by a
      spectrophotofluorimetric evaluation of Evans Blue dye extravasation. As compared
      to sham-operated controls, SAH determined a significant BBB permeability change
      beginning 36 hours after SAH, peaking at 48 hours, and normalizing on day 3. This
      study provides a quantitative description of the temporal progression and
      recovery of BBB dysfunction after SAH. These results have implications for the
      management of aneurysm patients and for assessing the rationale and the
      therapeutic window of new pharmacological approaches.

PMID- 10898367
TI  - CT-based needle marking of superficial intracranial lesions for minimal invasive
      neurosurgery.
AB  - A CT-based method of marking superficial intracranial lesions with a needle is
      presented. This form of neuronavigation can be applied in every neurosurgical
      centre. Owing to its rapid application it is also suitable for cases of
      emergency. The neurosurgical approach can be centred precisely over the lesion
      providing for a minimally invasive operation. The method has proved its efficacy
      in numerous cases of haematomas and cystic lesions.

PMID- 10898368
TI  - Intraoperative test stimulation with a modified implantable pulse generator in
      deep brain stimulation.
AB  - A modified implantable pulse generator (MIPG) for intraoperative test stimulation
      in chronic deep brain stimulation is described. The MIPG can be used for bipolar
      stimulation with quadripolar electrodes. The device is programmed and controlled
      with a standard console programmer. It can also be used for postoperative test
      stimulation with externalized electrodes. In our experience, the MIPG has several
      advantages as compared to the screener that is usually used.

PMID- 10898369
TI  - Primary intracranial malignant schwannoma of trigeminal nerve. A case report with
      review of the literature.
AB  - The authors report a rare case of primary intracranial malignant schwannoma of
      the trigeminal nerve occuring in a 30-year-old woman without von Recklinghausen's
      neurofibromatosis (VRNF). The tumour arose from the intracranial part of the left
      trigeminal nerve, without skull base destruction. The tumour was partially
      removed operatively, followed by focal 50 Gy irradiation, but unfortunately the
      tumour showed rapid regrowth. A second operation was attempted, but she died of
      cerebral infarction soon after operation. Histologically, the original tumour was
      characterized by the presence of foci of extremely high cellularity, pleomorphism
      and mitosis in an otherwise typical benign schwannoma. Immunohistochemically, the
      tumour cells were positive for S-100 protein even in the atypical areas,
      suggesting the tumour to be of Schwann cell origin. However, the recurrent tumour
      was composed of undifferentiated spindle cells, which were negative for S-100
      protein. Thus, it is possible to consider that the S-100 protein expression could
      reflect the degree of differentiation of Schwann cells. Furthermore, the
      postoperative irradiation might have exacerbated the malignant progression in the
      present case.

PMID- 10898370
TI  - Primary non-Hodgkin's lymphoma of the cranial vault presenting with unilateral
      proptosis.

PMID- 10898371
TI  - Delayed cerebral radiation necrosis occurring twice at different regions and
      times in a patient with a metastatic brain tumour.
AB  - No case of histopathologically confirmed delayed cerebral radiation necrosis
      (DCRN) that occurred twice at different regions and times in the same patient has
      been previously reported. We present a patient with such a rare clinical course
      and who is surviving long-term (over 13 years) with a history of a distant
      metastasis of a malignant tumour. To diagnose DCRN preoperatively was very
      difficult. However, surgical extirpation seemed to be effective for DCRN. The
      patient is still in a good performance status after surgery.

PMID- 10898372
TI  - Ependymal cyst occluding the Foramen Magendie.

PMID- 10898373
TI  - Mental health services for people with intellectual disability: a conceptual
      framework.
AB  - The present paper discusses the application of the 'matrix model' to mental
      health services for people with intellectual disability. There is great
      variability between the service models in this area, which makes comparisons and
      conclusions difficult. The present model facilitates the breaking down of these
      complexities into understandable parts so that future directions for research,
      service planning and delivery can be logical, coherent and evidence-based.

PMID- 10898374
TI  - Factors affecting the risk of behaviour problems in children with severe
      intellectual disability.
AB  - In order to examine the importance of a range of potential risk factors for
      behaviour problems in children with severe intellectual disability, a sample was
      identified by the administration of a screening version of the Vineland Adaptive
      Behaviour Scales (VABS) to the parents of children aged 4-11 years attending six
      special needs schools in three adjacent inner London boroughs. Parents whose
      children had a VABS standard score of < or = 50 were interviewed using the
      Disability Assessment Schedule and both parents and teachers completed the
      Aberrant Behaviour Checklist. Most behaviour problems were more common in
      ambulant children, but problems less dependent on the ability to walk, such as
      sleeping difficulties, screaming and self-injury, were equally common in ambulant
      and non-ambulant children. Among ambulant children, there were few significant
      associations between the severity of the child's behaviour problems and the age
      or sex of the child, the presence or absence of epilepsy, and various indices of
      socio-economic disadvantage. Sleeping difficulties, overactivity, self-injury,
      destructive behaviour and autistic features, such as social withdrawal and
      stereotypies, were strongly associated with skills deficits, but aggression,
      temper tantrums and general disruptive behaviour were not. Limitations in daily
      living skills were better predictors of behaviour problems than were poor
      communication skills.

PMID- 10898375
TI  - Behavioural and emotional difficulties in students attending schools for children
      and adolescents with severe intellectual disability.
AB  - BACKGROUND: For several decades, researchers and clinicians have been aware of an
      increased prevalence of psychiatric disorder in children with intellectual
      disability. However, there are few research studies exploring this issue.
      METHODS: The parents of 123 children attending schools for children with 'severe
      learning difficulties' completed the Developmental Behaviour Checklist (DBC) in
      order to identify those children with clinically significant behavioural and
      emotional problems. Comparisons were made with norms for the DBC and a range of
      child variables were investigated as possible correlates of disorder. RESULTS:
      Some 50.4% of the children scored above the cut-off on the DBC for psychiatric
      disorder. The child's severity of physical disability was related most strongly
      to parental ratings of behavioural and emotional problems. There were also
      effects for the child's age and the absence of Down's syndrome. CONCLUSIONS: The
      present study confirms previous research findings of a high prevalence of
      behavioural and emotional difficulties amongst children with intellectual
      disability, and identifies a number of correlates of disorder which require
      further investigation.

PMID- 10898376
TI  - Predictors of admission to a high-security hospital of people with intellectual
      disability with and without schizophrenia.
AB  - Admission to secure hospital facilities is a rare outcome for people with
      intellectual disability with or without concomitant psychosis. The present study
      compares people with mild intellectual disability with and without schizophrenia
      resident in the Scottish and Northern Irish State Hospital, Carstairs, to matched
      mild intellectual disability controls, also with and without schizophrenia, in
      the community. It is hoped that this study may identify socio-demographic,
      clinical or historical predictors which may lead to admission to secure hospital
      facilities for people with mild intellectual disability. One hundred and eight
      subjects were identified from two previous studies which concerned State Hospital
      patients and patients with intellectual disability with and without
      schizophrenia. Four experimental groups were derived: (1) 14 individuals with
      comorbid intellectual disability and schizophrenia who had been resident in the
      State Hospital; (2) 34 comorbid community control subjects; (3) 33 individuals
      with intellectual disability and no psychosis who had been resident in the State
      Hospital; and (4) 27 community control subjects with mild intellectual
      disability. The four groups were compared on a range of socio-demographic,
      historical and clinical variables obtained from case records and subject
      interviews. Relative to community controls, people with intellectual disability
      and no psychosis in the State Hospital are likely to be single, to have a later
      age of first psychiatric hospital admission, and to have a history of previous
      suicide attempts, alcohol abuse or drug misuse. Subjects with comorbid
      intellectual disability and schizophrenia in the State Hospital are more likely
      to be male, to have an early age of first psychiatric admission, and to have no
      family history of either schizophrenia or intellectual disability. Strategies
      aimed at addressing suicidal behaviour, alcohol and drug misuse amongst people
      with intellectual disability may facilitate a reduction in the number of
      admissions to high-security hospitals in the UK. In people with comorbid
      intellectual disability and schizophrenia, males with an early age of onset and
      no known family history are more likely to require care and treatment in a secure
      psychiatric setting. Such comorbid subjects may be suffering from a particular
      malignant form of schizophrenia, manifesting in childhood as cognitive impairment
      prior to the early onset of psychosis in teenage years.

PMID- 10898377
TI  - Incidence and course of dementia in people with Down's syndrome: findings from a
      population-based study.
AB  - The prevalence rate of Alzheimer's disease (AD) in people with Down's syndrome
      (DS) increases significantly with age. However, the nature of the early clinical
      presentation, course and incidence rates of dementia are uncertain. The aims of
      the present study were to investigate the characteristics of age-related clinical
      changes and incidence rates for dementia in a population-based sample of people
      with DS aged 30 years and older at the age of risk for dementia. A modified
      version of the Cambridge Examination for Mental Disorders of the Elderly
      informant interview was used to determine the extent and nature of changes in
      memory, personality, general mental functioning and daily living skill 18 months
      after a similar assessment At the time of the first assessment, the initial
      changes reported were predominately in behaviour and personality. At the second
      assessment, overall estimated incidence rates for frontal-like dementia were high
      (0.24), mainly in the younger groups, with incidence rates of AD, meeting both
      ICD-10 and DSM-IV criteria, of 0.04 predominately in the older groups. The
      present authors have hypothesized that the observed personality changes and the
      high estimated incidence rates of frontal-like dementia in the younger groups may
      indicate that functions served by the frontal lobes are the first to be
      compromised with the progressive development of Alzheimer-like neuropathology in
      people with DS.

PMID- 10898378
TI  - Hidden psychiatric morbidity in a vocational programme for people with
      intellectual disability.
AB  - The aim of the present study was to assess the point-prevalence of psychiatric
      disorders according to DSM-III-R criteria and the hidden morbidity in individuals
      with intellectual disability working in a vocational setting. The present study
      was carried out in a vocational centre in Southern Spain which is considered to
      be a model for social integration. One hundred and thirty workers with
      intellectual disability were interviewed by two experienced clinicians using the
      Assessment and Information Rating Profile, DSM-III-R criteria, and the General
      Assessment of Functioning and Clinical Global Impression scales. The point
      prevalence of psychiatric morbidity, hidden morbidity and treatment adequacy were
      estimated. Morbidity was hidden (i.e. not previously diagnosed) in 50% of
      psychiatric cases. Forty-two (32.3%) subjects had a psychiatric diagnosis with
      the following distribution: schizophrenia (17.7%), other psychotic disorders
      (9.23%), mood disorders (4.61%), adaptive disorders (2.31%), anxiety disorders
      (1.54%) and other psychiatric disorders (6.15%). Treatment was judged inadequate
      in 30% of subjects. The point-prevalence of psychiatric problems in a vocational
      setting in Spain was similar to that found in other environments. Hidden
      morbidity was similar to that found in primary care. The present study highlights
      the need for standardized instruments for psychiatric assessment in non-clinical
      settings as well as specific training in this area.

PMID- 10898379
TI  - Results of barbiturate antiepileptic drug discontinuation on antipsychotic
      medication dose in individuals with intellectual disability.
AB  - Five individuals with intellectual disability prescribed both a barbiturate
      antiepileptic drug (AED) and an antipsychotic medication were identified in a
      public residential facility. It was hypothesized that antipsychotic medication
      was prescribed at doses higher than necessary as a result of inadvertent
      barbiturate AED behavioural side-effects thought to be part of the underlying
      psychiatric or behavioural condition. To test this hypothesis, barbiturate AEDs
      were gradually reduced, and replaced with either carbamazepine or valproic acid,
      and antipsychotic medication was gradually reduced as well. Challenging
      behaviours, such as physical aggression, self-injurious behaviour and property
      destruction, were measured with a frequency count or partial interval recording,
      and retrospectively analysed for time periods of approximately 60 days before
      phenobarbital reduction, after phenobarbital discontinuation and after the lowest
      antipsychotic medication dose. Challenging behaviour collectively decreased by
      81.5% after barbiturate discontinuation, mean antipsychotic medication dose
      significantly decreased from 146 mg day(-1) (SD = 98) to 106 mg day(-1) (SD = 88)
      chlorpromazine equivalence, and antipsychotic medication was discontinued in the
      cases of two individuals. Compared to the prebarbiturate AED reduction period,
      challenging behaviour collectively decreased by 96.3% after the lowest
      antipsychotic medication dose, which confirmed that reduced antipsychotic
      medication was not achieved at the expense of behaviour deterioration. The data
      supported the hypothesis that discontinuation of barbiturate AEDs results in
      decreased challenging behaviour and less antipsychotic medication.

PMID- 10898380
TI  - Use of the atypical antipsychotics Olanzapine and Risperidone in adults with
      intellectual disability.
AB  - The present study was designed to monitor the use of atypical antipsychotics in
      adults with intellectual disability and to evaluate the clinical effectiveness of
      these drugs. Twenty-one patients were commenced on an atypical antipsychotic: 12
      on Olanzapine and nine on Risperidone. The ICD-10 diagnoses of the subjects were
      mild (13 cases) or moderate (8 cases) mental retardation, and psychiatric
      disorders (17 cases) with significant impairment of behaviour in 10 cases.
      Tolerability was good for 15 patients experiencing minimum or no side-effects,
      and medication was only stopped as a result of side-effects in one case. Clinical
      global outcome was rated as minimally improved or better for 16 cases. The
      present findings suggest that the atypical antipsychotics Olanzapine and
      Risperidone are well tolerated by patients with intellectual disability and
      psychiatric disorders, and are broadly effective against target symptoms.

PMID- 10898381
TI  - Association of a balanced chromosomal translocation (4; 12)(q21.3; q15),
      affective disorder and autism.
AB  - This case report describes a set of monozygotic twins with severe intellectual
      disability, autism and affective disorder with a balanced translocation between
      chromosomes 4 and 12. Their mother, who carries the same balanced translocation,
      had severe postnatal depression. The association between autism affective
      disorder and these chromosome break points has not been reported previously. The
      implications are discussed.

PMID- 10898382
TI  - Test battery for the diagnosis of dementia in individuals with intellectual
      disability. Working Group for the Establishment of Criteria for the Diagnosis of
      Dementia in Individuals with Intellectual Disability.
AB  - A working battery of tests for the diagnosis of dementia, which is applicable to
      most adults with intellectual disability, is proposed by an international Working
      Group. The battery, reflecting contemporary research and practice findings,
      includes scales for informant report of functioning and tests for direct
      assessment. The Working Group recommends the international use of the battery
      both as part of ongoing and new longitudinal research, and in clinical practice.
      The widespread use of a common battery will enhance communication and
      collaborative opportunities among researchers and clinicians at various sites,
      and will help to standardize diagnostic protocols and research findings. The
      collaborative evaluation of such a battery will address one of the greatest
      challenges in the field, that of differentiating change associated with ageing
      from that associated with dementia.

PMID- 10898383
TI  - Removal of precursors for disinfection by-products (Dbps)--differences between
      ozone- and OH-radical-induced oxidation.
AB  - Pre-oxidation is often applied to reduce the formation of disinfection by
      products (DBPs). The aim of pre-oxidation is to remove the centers of natural
      organic matter (NOM) which are responsible for the formation of DBPs. In this
      paper, the differences between ozone- and OH-radical-induced oxidation to remove
      DBP-precursors are compared. The experiments were done with water of the River
      Ruhr (Germany) with a concentration of dissolved organic carbon (DOC) of 2 mg/l.
      Ozonation was able to remove DBP precursors selectively. After application of an
      absorbed ozone mass of 1.5 mg/mg DOC, a reduction in the formation potential for
      (THM-FP) and in the formation potential for organic halogen adsorbable on
      activated carbon (AOX-FP) down to 68 and 73% of the initial concentration was
      achieved, respectively. A removal of NOM was not achieved using absorbed ozone
      masses between 0.5 and 1.5 mg/mg DOC. In the hydrogen peroxide/UV process, in
      which OH-radicals are the reactive species, an increase in the THM concentration
      was measured after application of this process with short irradiation times. The
      maximum value of the THM-FP was 20% higher than the initial THM-FP. After an
      irradiation time of 1,050 min and a hydrogen peroxide consumption of 5.6 mg/l,
      the THM-FP and AOX-FP decreased to 75 and 71% of the initial formation potential,
      respectively. There was no selective removal of DBP precursors because the DOC
      concentration decreased also to 75% of the initial DOC-concentration after 1,050
      min of irradiation.

PMID- 10898384
TI  - Some analytical problems encountered for trace elements determination in the
      airborne particulate matter of urban and rural areas.
AB  - The determination of trace elements (TE) in airborne particulate matter collected
      onto filters requires an accurate evaluation of the entire analytical procedure.
      Since many elements have to be determined at a few milligrams of air dust at
      nanogram levels, possible sources of error can arise from uncontrolled parameters
      such as blank of the filters, sample homogeneity, pre-analytical treatment,
      primary and comparator standards. These potential critical points are presented
      here and discussed on the basis of the experience developed in our laboratory in
      previous studies where several TE monitoring campaigns have been performed for
      air particulate matter collected in urban as well as in rural residential areas
      of north Italy. Instrumental neutron activation analysis (INAA) and
      electrothermal atomic absorption spectroscopy (ET-AAS) have been used for the
      investigation of more than 30 trace elements.

PMID- 10898385
TI  - Conservation practices in US agriculture and their implication for global climate
      change.
AB  - Increase in the use of conservation practices by agriculture in the United States
      will enhance soil organic carbon and potentially increase carbon sequestration.
      This, in turn, will decrease the net emission of carbon dioxide. A number of
      studies exist that calibrate the contribution of various individual, site
      specific conservation practices on changes in soil organic carbon. There is a
      general absence, however, of a comprehensive effort to measure objectively the
      contribution of these practices including conservation tillage, the Conservation
      Reserve Program and conservation buffer strips to an change in soil organic
      carbon. This paper fills that void. After recounting the evolution of the use of
      the various conservation practices, it is estimated that organic carbon in the
      soil in 1998 in the United States attributable to these practices was
      approximately 12,200,000 metric tons. By 2008, there will be an increase of
      approximately 25%. Given that there is a significant potential for conservation
      practices to lead to an increase in carbon sequestration, there are a number of
      policy options that can be pursued. These include education and technical
      assistance, financial assistance, research and development, land retirement and
      regulation and taxes.

PMID- 10898386
TI  - An inventory of historical mercury emissions in maritime canada: implications for
      present and future contamination.
AB  - Mercury is a longstanding concern in Maritime Canada due to high levels of
      contamination in a number of fish and bird species. The recycled component of
      past releases of anthropogenic mercury may be a significant source of ongoing
      pollution in many areas. Historical information on mercury releases can be used
      to quantify past and present anthropogenic contamination. We present an inventory
      of historical mercury emissions from anthropogenic sources in Maritime Canada for
      the years 1800-1995. Long-term trends in mercury emissions and the significance
      of the cumulative burden of mercury released from local sources are discussed.
      Emissions are calculated using both historical monitoring data and the
      application of emission factors. The nature of current anthropogenic sources of
      mercury is quite different than it was several decades ago when many of the
      existing policies governing mercury pollution were created. Our inventory
      illustrates that many of the most significant sources in the past such as the
      chlor-alkali industry, paint containing mercury additives, and pharmaceuticals,
      have been largely phased out with fossil fuel combustion and waste disposal
      remaining as the most significant modern sources. Atmospheric emissions in
      Maritime Canada peaked in 1945 (> 1,750 kg year-1), and again between 1965 and
      1970 (> 2,600 kg year-1). Cumulative releases of mercury from anthropogenic
      sources for the years 1800-1995 were between 115 and 259 t to the atmosphere
      alone, and 327-448 t when discharges to wastewater and effluents were included.
      Assuming that only 0.2% (Nriagu, 1994.) of these releases become part of the
      recycled fraction of current fluxes, we estimate that between 570 and 900 kg Hg
      year-1 is deposited in Maritime Canada from past anthropogenic sources. Modern
      sources within Maritime Canada contribute at least 405 kg year-1 to the total
      annual deposition of 1.71 t over the provinces of New Brunswick, Nova Scotia and
      Prince Edward Island, leaving approximately 735 kg year-1 from natural sources
      and long-range contamination. Further study is needed to verify these estimates
      and clarify the significance of natural and long-range sources of mercury in
      Maritime Canada.

PMID- 10898387
TI  - Effects of Cu2+ on root growth, cell division, and nucleolus of Helianthus annuus
      L.
AB  - The effects of different concentrations (10-5 - 10-2 M) of copper sulfate on root
      growth, cell division and nucleoli in root-tip cells of Helianthus annuus L. were
      investigated. Cu had an inhibitory effect on the root growth at 10-4 - 10-2 M
      during the entire treatment. Cu has toxic effects on chromosomal morphology
      including anaphase bridges and chromosome stickiness and on nucleoli, causing
      some similar silver-stained particulate material scattered in the nuclei. Once
      the nucleolus is poisoned, showing some silver-stained particles scattered in the
      nucleus, the root growth of H. annuus is obviously inhibited. And once more
      silver-stained particles appear in the nucleus, the root growth is almost or
      completely stopped. The possible mechanism of the Cu poisoning of root-tip cells
      of H. annuus is also briefly discussed.

PMID- 10898388
TI  - Electrochemical degradation of humic acid.
AB  - The treatment of natural water for drinking water production goes through the
      degradation of humic substances. In this study, humic acid, extracted from a peat
      area located at the margins of the Mogi Guacu River at Sao Paulo State, Brazil,
      was used to perform electro-oxidation essays in order to evaluate the
      possibilities of electrochemical methods in the degradation of humic substances.
      The working electrodes were dimensionally stable anodes (DSA) type with the
      following compositions: Ti/Ir0.3Ti0.7O2; Ti/Ru0.3Ti0.7O2; and
      Ti/Ir0.2Ru0.2Ti0.6O2. The electrolyses were performed by using a solution
      composed of an electrolyte support (0.1 mol l(-1) KCL) and 30 mg l-1 of the humic
      acid. Samples were taken during the electrolyses and analysed by the pH,
      transmittance, UV-vis spectra and chromatography. The results show that the
      Ti/Ru0.3Ti0.7O2 electrode presents the best performance considering the
      elimination of most of the electro-oxidation products after approximately 2 h of
      electrolysis at 40 mA cm(-2).

PMID- 10898389
TI  - The problem of arsenic interference in the analysis of soils for cadmium by
      inductively coupled plasma-optical emission spectrometry
AB  - Cadmium determination in soils that contain arsenic may be subject to
      interference. When this problem is not appreciated spurious results may be
      accepted as correct. Spectrometric methods for the quantitative determination of
      cadmium in the presence of arsenic were compared. Data are given for each method
      to demonstrate the problem of arsenic interference. Cadmium determination by
      Flame Atomic Absorption Spectrometry was free from arsenic interference. Cadmium
      determination by Inductively Coupled Plasma Spectrometry and Graphite Furnace
      Flame Atomic Absorption Spectrometry were subject to interference at arsenic
      concentrations greater than 50 microg l-1 and 10 mg l-1, respectively. A strategy
      for cadmium determination in arsenic contaminated soils is suggested.

PMID- 10898390
TI  - Polycyclic aromatic hydrocarbons in storm runoff from urban and coastal South
      Carolina.
AB  - Stormwater runoff was collected in urbanized areas of South Carolina to
      investigate the levels and sources of polycyclic aromatic hydrocarbons (PAHs).
      Mean concentrations of total PAHs in runoff (sum(PAHs), 14 compounds), determined
      by gas chromatography-mass spectrometry, were 5590 ng/l in the city of Columbia
      and 282 ng/l in the coastal community of Murrells Inlet. Lower concentrations
      were found in estuarine water at Murrells Inlet (mean = 35 ng/l) and at
      undeveloped North Inlet estuary (13 ng/l). The PAH profiles in Columbia and
      Murrells Inlet runoff were similar to those of atmospheric particulate matter and
      unlike those in used crankcase oil. Examination of the aliphatic fraction of
      Columbia runoff samples by gas chromatography with flame ionization detection
      showed patterns that were more similar to used crankcase oil than to urban
      aerosols.

PMID- 10898391
TI  - Relationship of hair calcium concentration to incidence of coronary heart
      disease.
AB  - This study was designed to evaluate whether hair calcium concentration reflects
      the mortality from coronary heart disease on a UK-wide basis and to determine the
      effect--if any--of environmental factors which might affect calcium metabolism on
      this relationship. The study was based on our earlier findings of an inverse
      relationship between hair calcium concentration and that in the intima of the
      aorta and the association of high aorta calcium with severe alterations to the
      vessel walls which was found never to co-exist with hair calcium concentrations
      greater than 700 ppm. Hair samples were collected from 4393 males in an ethically
      approved study in 40 different health districts. These covered the range in known
      prevalence of heart disease as reflected in the published standardised mortality
      ratios (SMR). Data on water hardness were obtained from the Water Authorities and
      on mean annual sunshine hours from the Meteorological Office. Statistical
      analysis was by regression and multivariate regression techniques. Hair calcium
      was determined by XRF analysis and the accuracy validated by means of certified
      reference samples. Significant relationships were found between health district
      and county SMR and their respective mean hair calcium concentrations accounting
      for 37 and 55% of their respective variances in SMR. Water hardness and sunshine
      hours accounted for 39 and 49% of the variance in mortality from CHD. In
      combination they accounted for 54% of the variance and with the inclusion of hair
      calcium 65%. South-east England had the highest hair calcium, the hardest water
      and the most sunshine hours and the lowest mortality from CHD. The converse was
      true of Scotland. Hair calcium concentration did reflect the risk of CHD on a
      population basis and was strongly influenced by both the hardness of the water
      supply and the annual sunshine hours which also independently affected the SMR
      for CHD.

PMID- 10898392
TI  - Heavy metals in human primary teeth: some factors influencing the metal
      concentrations.
AB  - Human primary teeth have been used as indicators of heavy metal exposure for
      several decades, but the knowledge about the influence of factors such as tooth
      type and the presence of caries and roots on metal concentrations is limited.
      Samples of tooth powder from more than 1200 Norwegian primary teeth without
      fillings have been analyzed for lead, zinc and cadmium content, and 554 of them
      for mercury. The material represents all groups of tooth types (incisors, canines
      and molars), carious and non-carious teeth, and teeth with and without roots.
      Here we investigate how tooth group and the presence of caries and roots are
      related to metal concentrations in the teeth. We find that carious teeth have
      higher metal concentrations than non-carious teeth; the difference was
      statistically significant for lead, mercury and zinc. Teeth with roots have
      higher lead and zinc concentrations than teeth without roots. We find differences
      in metal concentrations between the tooth groups for lead, mercury and zinc.
      Significant, positive correlations are found between lead and the three other
      metals and between mercury and zinc. We conclude that metal concentrations in
      primary teeth are affected by the presence of caries and roots and by tooth
      group.

PMID- 10898393
TI  - Short-term effects of biosolid and municipal solid waste applications on heavy
      metals distribution in a degraded soil under a semi-arid environment.
AB  - Digested biosolid (SS) and municipal solid waste (MSW) were surface-applied to a
      degraded carbonated soil, under semi-arid environment, at rates of 0 and 80
      Mg/ha, to determine the changes in organic matter and in the distribution of
      heavy metals in the topsoil, 1 year after its application. Waste application
      slightly increased the organic matter content and improved the composition of
      humic fractions in the treated soils, mainly in the MSW amended plots. A
      sequential extraction method (Tessier et al., 1979) was used to determine the
      distribution of Cd, Cr, Cu, Ni, Pb and Zn in both the waste and the
      amended.soils. Waste application had little effect on the total concentration of
      Ni and Cr in the treated soils as a consequence of the low availability of these
      metals in the wastes. A considerable increase of Cd, Cu, Pb and Zn was observed
      as a consequence of the high content and/or high availability of these metals in
      the wastes. The more labile fraction (exchangeable fraction) of all metals
      studied increased slightly (< 1.5 mg/kg) when SS and MSW were added. However, a
      remarkable increase in the Fe/Mn oxide fraction of Cd, Cu and Pb and in the
      organic fraction of Zn were noted in treated plots, this increase being higher in
      the MSW treated soils.

PMID- 10898394
TI  - Determination of 14 elements in Taiwanese bones.
AB  - The objective of this study was to measure the concentration of 14 elements in
      human bone and investigate the affecting factors. This study aims to establish a
      database of elements in Taiwanese bone. Seventy-seven bone samples were taken
      from 70 subjects who were undertaking various bone surgeries from a medical
      center in central Taiwan. Bone samples were pretreated using microwave digestion
      and then, after determining the optimal conditions for analysis, fourteen
      elements were analyzed using Inductively Coupled Plasma-Atomic Emission
      Spectroscopy (ICP-AES). Results showed that Ca had the highest concentration,
      followed by Mg and Zn. The lowest concentrations were of Mn, followed by Cd and
      Co. There was a positive correlation between the frequency of seafood intake and
      presence of all the 14 elements in human bone. There were several elements that
      had positive inter-correlation: As with Co; Al, Ag and Ca; Ni with Co, Mn and Al;
      Co with Al, Ag and Ca; Mn with Cr and Cu; Cr with Cu; Mg with Ca; Al with Ag and
      Ca; Ag with Ca; and also Zn with Mg. There were no significant differences found
      between concentrations of elements and etiology of bone disease and age. The
      authors suggest that further studies be conducted to establish a normal value of
      elements in human bone in Taiwan. This will greatly benefit the understanding of
      the relationship between disease pattern and elements in human bone.

PMID- 10898395
TI  - Radiocesium discharges and subsequent environmental transport at the major US
      weapons production facilities.
AB  - Radiocesium is one of the more prevalent radionuclides in the environment as a
      result of weapons production-related atomic projects in the USA and the former
      Soviet Union. Radiocesium discharges during the 1950s account for a large
      fraction of the historical releases from US weapons production facilities.
      Releases of radiocesium to terrestrial and aquatic ecosystems during the early
      years of nuclear weapons production provided the opportunity to conduct
      multidisciplinary studies on the transport mechanisms of this potentially
      hazardous radionuclide. The major US Department of Energy facilities (Oak Ridge
      Reservation in Tennessee, Hanford Site near Richland, Washington, and Savannah
      River Site near Aiken, South Carolina, USA) are located in regions of the country
      that have different geographical characteristics. The facility siting provided
      diverse backgrounds for the development of an understanding of environmental
      factors contributing to the fate and transport of radiocesium. In this paper, we
      summarize the significant environmental releases of radiocesium in the early
      years of weapons production and then discuss the historically significant
      transport mechanisms for 137Cs at the three facilities that were part of the US
      nuclear weapons complex.

PMID- 10898396
TI  - Total arsenic, lead, and cadmium levels in vegetables cultivated at the Andean
      villages of northern Chile.
AB  - Various vegetables (broad beans, corn, potato, alfalfa and onion) were sampled in
      northern Chile, Antofagasta Region. They are the basis of human nutrition in this
      region and of great relevance to human health. This region is characterized by
      volcanic events (eruptions, thermal springs, etc.). Most of the vegetables
      cultivated in this area enter the local markets for a population of approximately
      4000 people, whose ancestors were mainly atacamenos and quechuas (local
      indigenous people). The cadmium and lead in these foods was determined by
      differential pulse anodic stripping voltammetry (DPASV). Results indicate that
      the highest concentration of Pb and Cd are in the potato skin, while the edible
      part of the potatoes contained a lower concentration of these metals. The INAA
      analyses of As in the vegetables from Socaire and Talabre, two towns located
      close to active volcanoes (e.g. Lascar), show a very high As content: 1850
      microg/kg in corn (Socaire) and 860 microg/kg in potatoes (+ skin) (Talabre).
      These values exceed the National Standard for arsenic (500 microg/kg) by
      approximately 400% and 180%, respectively. In general, the data show a
      concentration of Pb greater than Cd with the potential for some vegetables to
      accumulate heavy metals, The values, expressed in fresh weight, vary from 0.2 to
      40 microg/g for Cd and from 0.6 to 94 microg/g for Pb. These concentration
      intervals, except that of arsenic, are within the recommended standards in the
      Food Sanitary Regulation (Decree 977), which, expressed as fresh weight, must be
      equal to or smaller than 500 microg/kg for Pb. There is no legal standard for Cd.

PMID- 10898397
TI  - Total arsenic, lead, cadmium, copper, and zinc in some salt rivers in the
      northern Andes of Antofagasta, Chile.
AB  - The pre-Andes water in the region of Antofagasta is the main drinking and
      irrigation water source for approximately 3000 Atacamena (indigenous) people. The
      concentration for soluble elements (filtration in field through a 0.45-microm
      filter) was: Cd < 0.1 ng/ml; Pb < 0.5 ng/ml; and Zn and Cu between 1 and 10
      ng/ml. In particulate material the concentrations were: for Cd < 0.1 ng/ml; for
      Pb < 0.3 ng/ml; and for Zn and Cu less than 1 ng/ml. The total content of these
      elements is far below the international recommendations (WHO) and the national
      standards (N. Ch. 1333 mod. 1987 and 409-1 of 1984). On the other hand, in some
      rivers a very high arsenic concentration was found (up to 3000 ng/ml) which
      exceed more than 50 times the national standard. In order to verify the
      analytical results, inter-laboratory and comparison with different determination
      methods have been done.

PMID- 10898398
TI  - Biomonitoring of trace elements with lichens in Veneto (NE Italy).
AB  - The concentrations of 13 elements in peripheral parts of the epiphytic lichen
      Xanthoria parietina were measured at 200 stations of Veneto (NE Italy). For each
      element, two maps are presented, showing, respectively, geographic patterns and
      deviations from background levels. The results are summarized by a map, showing
      the joint distribution of elements with concentrations close to Italian
      backgrounds, and of those strongly deviating from background levels. The results
      allow selection of high-risk areas for instrumental monitoring.

PMID- 10898399
TI  - Categorical mapping of marine eutrophication based on ecological indices.
AB  - The present work is concerned with the development of methodological procedures
      for studying the spatial distribution of eutrophication in the marine
      environment. Seven ecological indices (S, number of phytoplankton species; N,
      total number of individuals; D(Mg), Margalef's index; D(Mn), Menhinick's index;
      D(Od), Odum's species per thousand individuals; H', Shannon's Diversity index; E,
      Evenness index), based on phytoplankton community data collected from Saronicos
      Gulf, Greece were used for describing the eutrophication state of the sea
      environment. A representation of the spatial distribution for each ecological
      index was developed using the Inverse Distance Weighted (IDW) interpolation
      method. A eutrophication scale for each index was also developed for indicating
      four different trophic levels in the marine environment (eutrophic, upper
      mesotrophic, lower-mesotrophic, oligotrophic); categorization of the interpolated
      values of each index resulted in a clear illustration of these trophic levels on
      seven thematic maps. Two methodological procedures were finally applied for
      synthesizing the information of these thematic maps. The purpose was the
      development of a final map illustrating the spatial distribution of
      eutrophication in the study area. The first procedure was based on the
      integration of unsupervised and supervised classification methods, widely used in
      the field of remote sensing, while the second one on the overlay technique,
      simply carried out within the frame of a Geographical Information System (GIS).
      The hybrid unsupervised/supervised classification method can assess the optimal
      number of classes in which data values from simultaneously considered parameters
      could be allocated, while the overlay technique is an additive procedure not
      taking into account existing trends in the dataset. The advantages and
      disadvantages of each procedure are further discussed.

PMID- 10898400
TI  - Occurrence of triiodinated X-ray contrast agents in the aquatic environment.
AB  - High concentrations of adsorbable organic iodine (AOI) are found in municipal
      treatment plant effluents and surface waters by specific organic halogen
      determination. The high AOI is caused by widely used triiodinated X-ray contrast
      agents, which are very stable and hydrophilic. We have analysed specifically
      surface water influenced by a municipal treatment plant effluent, the surface
      water after bank filtration and raw drinking water. The X-ray contrast agents
      were determined by liquid chromatography-mass spectrometry with positive
      electrospray ionization after enrichment by solid phase extraction. Diatrizoate
      and iopromide, two triiodinated contrast agents are detectable in all samples,
      whereby the less polar component iopromide seems to be reduced during bank
      filtration. Just a trace of iopromide is identified in surface water after bank
      filtration and in the raw drinking water. Approximately 60% of the initial AOI is
      extractable and approximately 25% of the extractable AOI can be identified as
      specific triiodinated contrast agents.

PMID- 10898401
TI  - Energy consumption and exhaust emissions in mechanized timber harvesting
      operations in Sweden.
AB  - The study presents an estimation of the energy input and the amount of emissions
      to air due to fuel, chainsaw and hydraulic oil consumption by heavy duty diesel
      engine vehicles operating in forest logging operations in Sweden. Exhaust
      concentrations are given for carbon dioxide, carbon monoxide, nitrogen oxides,
      hydrocarbons and particulate matter. Three fuel types (rapeseed methyl ester,
      environmental class 1 and environmental class 3 diesel fuels) and two types of
      lubricating base oil (mineral- and vegetable-based) were examined. Energy input
      per unit of timber production (m3ub) was 82 MJ, 11% of which was due to energy
      consumption during the production phase of the fuel. Emissions during the whole
      life cycle of the fuels and the base oils are included in the study. The highest
      CO2 and NOx emissions occurred when rapeseed methyl ester was used as fuel
      together with rapeseed as base oil for chainsaw and hydraulic oil. The highest HC
      and CO emissions occurred when environmental class 3 diesel fuel was used.

PMID- 10898402
TI  - 137Cs distribution and geochemistry of Lena River (Siberia) drainage basin lake
      sediments.
AB  - The Lena River is the second largest river that discharges into the Arctic Ocean.
      It is therefore important to determine not only the direct impact its discharge
      has on the 137Cs concentration of the Arctic, but also the potential its drainage
      basin has as a 137Cs source. 137Cs surface sediment concentrations and inventory
      values, which range from 4.97 to 338 Bq kg(-1) and 357 to 1732 Bq m(-2),
      respectively, were determined for the Lena River drainage basin lake samples, via
      gamma analysis. The average geochemical and mineralogical composition of a subset
      of samples was also determined using neutron activation analysis, X-ray
      diffraction and X-ray fluorescence spectrometry techniques. Results of these
      geochemical analyses allowed for the identification of key geochemical factors
      that influence the distribution of 137Cs in the Lena River drainage basin. 137Cs
      profiles indicate that Lena River drainage basin lacustrine sediments serve as a
      record of 137Cs fallout. Based on the downcore 137Cs, %illite, %smectite, %Al and
      %Mn distribution patterns, it was concluded that a small fraction of non
      selectively bound 137Cs was remobilized at depth in some cores. Inconsistencies
      between the actual 137Cs fallout record and the 137Cs profiles determined for the
      lake sediments were attributed to 137Cs remobilization in subsurface sediments.
      In addition to establishing the agreement between the global atmospheric fallout
      record and the downcore 137Cs distribution patterns determined for these
      sediments, results indicate that 137Cs deposited during periods of maximum
      atmospheric release was buried and is not susceptible to surface erosion
      processes. However, mean 137Cs concentrations of the lacustrine surface sediments
      (125 Bq kg(-1)) are still significantly higher than those of the nearby Lena
      River estuary (11.22 Bq kg(-1)) and Laptev Sea (6.00 Bq kg(-1)). Our study
      suggests that the Lena River drainage basin has the potential to serve as a
      source of 137Cs to the adjacent Arctic Ocean.

PMID- 10898403
TI  - Volatile organic compounds in indoor environments in Mumbai, India.
AB  - Air samples, representing different types of indoor environments, were collected
      and analyzed for eight hydrocarbons namely, n-hexane, benzene, heptane, toluene,
      p- and o-xylene, ethyl benzene and n-decane using a cryogenic preconcentration
      system and a gas chromatograph with a flame-ionization detector. Simultaneous
      outdoor samples were also collected to determine indoor to outdoor (I/O) ratios
      for every compound at each location. In all, seven different types of indoor
      environments were investigated for VOC levels. Toluene concentration levels were
      found to be high in a hall which was recently renovated. The indoor environment
      of a kitchen in which a kerosene stove was used and smoker's rooms showed high
      levels of benzene. The concentrations of VOCs during painting were found to be
      high and the levels of VOCs depended on the type of paint used. The study
      revealed that the indoor concentrations of selected VOCs on occasions could be
      significantly high due to various sources. The data presented here can be useful
      in developing air quality standards for indoor air.

PMID- 10898404
TI  - Elemental and radioactive analysis of commercially available seaweed.
AB  - Edible seaweed products have been used in many countries, specifically Japan, as
      a food item. Recently these products have become popular in the food industry
      because of a number of interesting medicinal properties that have been associated
      with certain edible marine algae. Very little control exists over the composition
      of these products, which could be contaminated with a number of agents including
      heavy metals and certain radioactive isotopes. Fifteen seaweed samples (six local
      samples from the coast of British Columbia, seven from Japan, one from Norway and
      one undisclosed) were obtained. All samples were analyzed for multiple elements,
      using ICP mass spectrometry and for radioactive constituents. It was found that
      six of eight imported seaweed products had concentrations of mercury orders of
      magnitude higher than the local products. Lead was found at somewhat higher
      concentrations in only one local product. Laminaria japonica had the highest
      level of iodine content followed by Laminaria setchellii from local sources. Only
      traces of cesium-137 were found in a product from Norway and radium-226 was found
      in a product from Japan. Arsenic levels were found to be elevated. In order to
      estimate the effect of these levels on health, one needs to address the
      bioavailability and the speciation of arsenic in these samples.

PMID- 10898405
TI  - The long QT syndromes: genetic basis and clinical implications.
AB  - It is becoming clear that mutations in the KVLQT1, human "ether-a-go-go" related
      gene, cardiac voltage-dependent sodium channel gene, minK and MiRP1 genes,
      respectively, are responsible for the LQT1, LQT2, LQT3, LQT5 and LQT6 variants of
      the Romano-Ward syndrome, characterized by autosomal dominant transmission and no
      deafness. The much rarer Jervell-Lange-Nielsen syndrome (with marked QT
      prolongation and sensorineural deafness) arises when a child inherits mutant
      KVLQT1 or minK alleles from both parents. In addition, some families are not
      linked to the known genetic loci. Cardiac voltage-dependent sodium channel gene
      encodes the cardiac sodium channel, and long QT syndrome (LQTS) mutations prolong
      action potentials by increasing inward plateau sodium current. The other
      mutations cause a decrease in net repolarizing current by reducing potassium
      currents through "dominant negative" or "loss of function" mechanisms.
      Polymorphic ventricular tachycardia (torsade de pointes) is thought to be
      initiated by early after-depolarizations in the Purkinje system and maintained by
      reentry in the myocardium. Clinical presentations vary with the specific gene
      affected and the specific mutation. Nevertheless, patients with identical
      mutations can also present differently, and some patients with LQTS mutations may
      have no manifest baseline phenotype. The question of whether the latter situation
      is one of high risk for administration of QT prolonging drugs or during
      myocardial ischemia is under active investigation. More generally, the
      identification of LQTS genes has provided tremendous new insights for our
      understanding of normal cardiac electrophysiology and its perturbation in a wide
      range of conditions associated with sudden death. It seems likely that the
      approach of applying information from the genetics of uncommon congenital
      syndromes to the study of common acquired diseases will be an increasingly
      important one in the next millennium.

PMID- 10898406
TI  - Techniques characterizing the coronary atherosclerotic plaque: influence on
      clinical decision making?
AB  - The composition of the atherosclerotic lesion rather than the degree of stenosis
      is currently considered to be the most important determinant for acute clinical
      events. Modalities capable of characterizing the atherosclerotic lesion may be
      helpful in understanding its natural history and detecting lesions with high risk
      for acute events. Speaking grossly, three histologic features of the vulnerable
      plaque have been reported: size of the atheroma, thickness of the fibrous cap,
      and inflammation. Imaging techniques are currently being deployed and are under
      development to aid visualization of the vulnerable coronary plaque. Most of these
      diagnostic modalities have the potential to detect locally one or more of the
      three histologically defined features of vulnerable plaque. This review will
      focus on imaging techniques that have been developed to characterize the
      atherosclerotic lesion. Most catheter-based visualization techniques will provide
      insight into components of the local atherosclerotic plaque which may limit their
      predictive value for the occurrence of a clinical event. Therefore, the clinical
      relevance of these imaging tools will be discussed.

PMID- 10898407
TI  - Coronary microembolization.

PMID- 10898408
TI  - Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor
      drugs in male patients with stable angina.
AB  - OBJECTIVE: We sought to study the effects of a single oral dose of sildenafil
      citrate (50 mg) on blood pressure (BP) in men taking the nitric oxide (NO) donor
      drugs isosorbide mononitrate (ISMN) or glyceryl trinitrate (GTN) for stable
      angina. BACKGROUND: Sildenafil, a selective phosphodiesterase type 5 inhibitor,
      is an orally effective treatment for erectile dysfunction. The presence of
      phosphodiesterases in the vasculature suggests the possibility of an interaction
      between sildenafil and NO donor drugs. METHODS: Two double-blind, placebo
      controlled, randomized, two-way crossover trials were undertaken. Sixteen male
      patients received oral ISMN (20 mg twice a day) for five to seven days before
      their dose of sildenafil or placebo and continued receiving ISMN daily until
      administration of the alternate drug seven days later. For the second study, 15
      male patients received sublingual GTN (500 microg) 1 h after sildenafil or
      placebo on each of two study days, which were seven days apart. Sitting or
      standing BP was measured before and for 6 h after the administration of the study
      drug. RESULTS: The effects of sildenafil plus ISMN on BP (standing mean maximum
      reductions from baseline in systolic/diastolic BP, -52/-29 mm Hg) were greater
      than the effects of placebo plus ISMN on BP (-25/-15 mm Hg; p < 0.001).
      Sildenafil plus GTN also resulted in greater sitting mean maximum reductions from
      baseline in systolic/diastolic BP (-36/-21 mm Hg) compared with placebo plus GTN
      (-26/-12 mm Hg; p < 0.01). CONCLUSIONS: Coadministration of sildenafil with ISMN
      or GTN produced significantly greater reductions in BP than ISMN or GTN alone.
      Based on these data, sildenafil should not be administered to patients taking
      nitrates.

PMID- 10898410
TI  - Lack of association of C-reactive protein and coronary calcium by electron beam
      computed tomography in postmenopausal women: implications for coronary artery
      disease screening.
AB  - OBJECTIVES: We sought to test the hypothesis that C-reactive protein, a marker of
      inflammation, would correlate positively with coronary calcium, a marker of
      atherosclerosis, in postmenopausal women. BACKGROUND: High sensitivity testing
      for C-reactive protein (hsCRP) has recently been shown in large population
      studies to predict cardiac events in asymptomatic postmenopausal women. Coronary
      calcification determined by electron beam computerized tomography (EBCT) has also
      been suggested to be predictive of cardiac events in women. METHODS: We performed
      hsCRP testing and determined calcium scores by EBCT in 172 asymptomatic
      postmenopausal women (mean age: 64.5 +/- 7.9 years) at risk for cardiac disease.
      Risk factors were determined by history, physical, electrocardiogram, exercise
      testing, and lipoprotein profiles. RESULTS: Calcium scores ranged from 0 to
      2,618. For analysis, calcium scores were divided into three groups; none (0 to
      10), minimal (>10 to 50), and significant (>50). Overall, there was no
      significant positive relationship between hsCRP level and calcium score.
      Specifically, the hsCRP levels (mg/dl) were 0.24 +/- 0.43, 0.33 +/- 0.47 and 0.17
      +/- 0.32 (medians 0.11, 0.15, and 0.06) for women with none, minimal, and
      significant coronary calcification, respectively. In subgroup analysis, a similar
      lack of positive association was observed after stratification by smoking status
      and by hormone replacement therapy use, two factors known to increase hsCRP.
      CONCLUSIONS: In contrast to our a priori hypothesis, we found no evidence of a
      positive association between hsCRP and calcium score by EBCT. These data thus
      raise the possibility that hsCRP and EBCT calcium score reflect different
      pathologic processes, an issue with implications for coronary artery disease
      screening.

PMID- 10898409
TI  - Exercise testing and electron beam computed tomography in the evaluation of
      coronary artery disease.
AB  - OBJECTIVES: This study compared coronary artery calcium (CC) as detected by
      electron beam computed tomography (EBCT) with conventional stress testing in the
      evaluation of patients with symptoms suggestive of coronary artery disease (CAD).
      BACKGROUND: Exercise electrocardiogram treadmill stress testing (treadmill-ECG)
      is limited by its requirement of a normal resting ECG and the ability of the
      patient to exercise adequately. The addition of myocardial imaging agents such as
      technetium improves the sensitivity and specificity but substantially increases
      the cost and prolongs the testing time. The use of EBCT provides a noninvasive
      and rapid method for identifying the presence and amount of CC, which has been
      shown to be related to atherosclerosis, and may provide additional information in
      combination with more traditional noninvasive testing methods. METHODS: A total
      of 97 patients underwent technetium stress testing (technetium-stress), treadmill
      ECG, and EBCT coronary scanning within three months of coronary angiography for
      the evaluation of chest pain. RESULTS: The relative risk (RR) of obstructive
      angiographic CAD for an abnormal test was higher for EBCT (4.53) than either
      treadmill-ECG (1.72) or technetium-stress (1.96). The low specificity of EBCT
      (47%) was improved by the addition of treadmill-ECG (83%, p < 0.05). CONCLUSIONS:
      Electron beam computed tomography has a higher diagnostic ability than either
      treadmill-ECG or technetium-stress for the detection of obstructive angiographic
      CAD. Electron beam computed tomography is an accurate and noninvasive alternative
      to traditional stress testing for the detection of obstructive CAD in symptomatic
      patients.

PMID- 10898411
TI  - Noninvasive detection of coronary artery stenosis using contrast-enhanced three
      dimensional breath-hold magnetic resonance coronary angiography.
AB  - OBJECTIVES: The purpose of this study was to evaluate a contrast-enhanced three
      dimensional (3D) breath-hold magnetic resonance (MR) technique for detection of
      coronary artery stenoses. BACKGROUND: The accuracy of previously published MR
      coronary angiography protocols varies widely. Recently, coronary artery imaging
      using T1-shortening contrast agent has become possible, but so far there are no
      data concerning its clinical application. METHODS: Magnetic resonance coronary
      angiography was performed in 50 patients with suspected coronary artery disease.
      Magnetic resonance data acquisition using an ultrafast 3D gradient-echo sequence
      lasted over 32 heartbeats within one single breath-hold. Twenty milliliters of
      gadopentetate dimeglumine was injected at a flow rate of 1 ml/s for two
      successive studies covering the main coronary arteries in single-oblique planes.
      Stenosis assessment by MR was compared with significant (diameter stenosis > 50%)
      stenoses on X-ray angiography. Evaluation was limited to the proximal and mid
      coronary artery segments. RESULTS: Two hundred sixty-eight of 350 artery segments
      (76.6%) could be evaluated. Left circumflex coronary artery was only evaluable in
      50% of cases by MR. In the evaluable segments, 48 of 56 stenoses and 193 of 212
      nonstenotic segments were correctly classified by MR. On a patient basis, MR
      correctly identified 34 of 36 patients with and 8 of 14 patients without
      significant coronary stenoses as demonstrated by X-ray angiography (sensitivity
      94.4%, specificity 57.1%). CONCLUSIONS: Oblique projection contrast-enhanced MR
      coronary angiograms obtained within one single breath-hold permit identification
      of patients with coronary stenoses in the proximal and mid segments of the major
      coronary arteries with satisfactory accuracy.

PMID- 10898412
TI  - Ten-year experience with early angioplasty in 759 patients with acute myocardial
      infarction.
AB  - OBJECTIVES: How effective and safe is rescue percutaneous transluminal coronary
      angioplasty [PTCA] compared with primary PTCA, and is it cost effective?
      BACKGROUND: In acute myocardial infarction (AMI), primary PTCA has been shown to
      be beneficial in terms of clinical outcome. In contrast, the value of rescue PTCA
      has not been established. METHODS: In a retrospective analysis, we compared the
      angiographic and clinical outcomes of 317 consecutive patients who had rescue
      PTCA approximately 90 min after failed thrombolysis and 442 patients treated with
      primary PTCA. An estimation of interventional costs was compared with the
      strategies of primary and rescue PTCA or with the strategy of thrombolysis with
      rescue PTCA, when indicated. RESULTS: Baseline characteristics between primary
      and rescue PTCA were comparable for most variables. Treatment delay was longer
      for patients who had rescue PTCA: 240 min. versus 195 min. Coronary patency after
      PTCA was comparable: 90.2% for rescue PTCA and 91.4% for primary PTCA (p = 0.67,
      power 71.9%). In-hospital mortality rates were 4.7% and 6.6%, respectively (p =
      0.37). Also, the other complications were fairly similar during the in-hospital
      phase and during one-year follow-up. Predictors of death were age, infarct size,
      localization of AMI, failed PTCA and left main stem occlusion. The estimated
      interventional costs during one-year follow-up were $7,377 for primary PTCA and
      $8,246 for rescue PTCA: difference $869 (11.7%). CONCLUSIONS: In this
      retrospective analysis of 759 patients with AMI, rescue angioplasty early after
      failed thrombolysis seems to be as effective and safe as primary PTCA. In the
      present evaluation, interventional costs of primary PTCA are less than those of
      rescue PTCA (p = 0.0001).

PMID- 10898413
TI  - The effects of intracoronary brachytherapy on the natural history of
      postangioplasty dissections.
AB  - OBJECTIVES: The aim of this study was to determine the natural history of
      postangioplasty intravascular ultrasound (IVUS)-detected dissections and to
      assess the influence of intracoronary beta-radiation on dissection resolution.
      BACKGROUND: Intracoronary radiotherapy is considered to impair exaggerated vessel
      healing. Conversely, excessive healing impairment may increase the risk of
      complications due to unhealed dissection. Alternatively, residual dissection may
      represent an innocent marker of adequate therapy. METHODS: Immediate
      postangioplasty and six-month follow-up IVUS studies of 94 patients in the IVUS
      substudy of the MultiVitamins and Probucol (MVP) trial and 26 nonstented patients
      in the Beta Energy Restenosis Trial (BERT) were analyzed for the presence or
      absence of dissection. RESULTS: Of the 28 patients with postangioplasty
      dissections in MVP, only one had evidence of residual dissection at six months
      (95% confidence interval [CI] for failure rate 0.2%; 20.2%). Conversely, 9 of 16
      dissections had healed in BERT (95% CI for failure rate 30.6%; 79.2%) (p <
      0.0002). Nevertheless, an index based on dissection arc and length demonstrated
      improvement in the irradiated patients. Irradiated patients with residual
      dissections showed significant increase in lumen area at six-months (5.10 +/-
      0.98 to 7.11 +/- 2.61 mm2, p < 0.02) not noted when there was resolution of the
      dissection (6.03 +/- 2.38 to 6.36 +/- 3.33 mm2, p = NS). In both groups the
      external elastic membrane area was unchanged at follow-up. CONCLUSIONS:
      Resolution appears to be the natural history of IVUS-detected dissections in most
      cases. Significant resolution of dissection occurs following intracoronary beta
      radiation as reflected in reduced dissection index at six-months in these
      patients, although significant impairment of vessel wall healing was noted.

PMID- 10898414
TI  - Late total occlusion after intracoronary brachytherapy for patients with in-stent
      restenosis.
AB  - OBJECTIVES: The study sought to determine the incidence and predictors of late
      total occlusion (LTO, >30 days) in-patients with in-stent restenosis who were
      treated with intracoronary radiation. BACKGROUND: Intracoronary radiation both
      with beta and gamma emitters has been shown to reduce recurrent in-stent
      restenosis. METHODS: We reviewed the records of 473 patients who presented with
      in-stent restenosis and who were enrolled in various radiation protocols, whether
      randomized to placebo versus radiation or entered into registries. There were 165
      placebo and 308 radiated patients, including both gamma and beta emitters.
      Maximum dose to the vessel wall was 30 to 55 Gy. Following radiation, all
      patients received antiplatelet therapy with aspirin and either ticlopidine or
      clopidogrel for one month. All patients completed at least six months of
      angiographic follow-up. RESULTS: The LTO was documented in 28 patients (9.1%)
      from the irradiated group versus 2 placebo patients (1.2%), p < 0.0001. The LTO
      rates were similar across studies and emitters. In the irradiated group, LTO
      presented as acute myocardial infarction in 12 patients (43%), unstable angina in
      14 (50%), and asymptotic in 2 (7%). Mean time to LTO was 5.4 +/- 3.2 months in
      the irradiated group versus 4.5 +/- 2.1 in placebo patients (p = NS). The overall
      rate of restenting for the entire study group at the time of radiation was 48.6%.
      Importantly, new stents were placed in 82% of the irradiated and in 100% of the
      placebo patients who presented with LTO. Multivariate analysis determined that
      new stenting was the main predictor of LTO. CONCLUSIONS: Intracoronary radiation
      for patients with in-stent restenosis is associated with a high rate of LTO.
      Restenting may contribute late thrombosis. Prolonged antiplatelet therapy (up to
      six months) should be considered for these patients.

PMID- 10898415
TI  - Six-month clinical and angiographic outcome after successful excimer laser
      angioplasty for in-stent restenosis.
AB  - OBJECTIVES: This study evaluated the clinical and angiographic six-month follow
      up after excimer laser coronary angioplasty (ELCA) for restenosed coronary
      stents. BACKGROUND: Excimer laser coronary angioplasty has recently been shown to
      be safe and efficient for the treatment of in-stent restenosis. METHODS: Ninety
      six consecutive patients successfully treated with ELCA within 141 stents were
      included in a six-month clinical and angiographic follow-up. RESULTS: During
      follow-up there was one sudden death and one patient with documented myocardial
      infarction. Angina pectoris classified as > or = Canadian Cardiovascular Society
      II reoccurred in 49 patients. Follow-up angiography was obtained in 89 patients
      (93%) with 133 stents. Quantitative coronary angiography revealed a mean diameter
      stenosis of 77 +/- 10% before intervention, 41 +/- 12% after laser treatment and
      11% +/- 12% after adjunctive percutaneous transluminal coronary angioplasty (p <
      0.001). Six months after ELCA the mean diameter stenosis had increased to 60 +/-
      26% (p < 0.001). A > or =50% diameter stenosis was present in 48 patients (54%);
      in 24 of these patients diameter stenosis was > or =70%. Total occlusions
      occurred in an additional 10 patients (11%). There was a trend toward an
      increased recurrent restenosis rate in patients with diabetes mellitus and long
      lesions or total occlusions (p = 0.059). Forty-eight patients (50%) received
      medical treatment after six months. Reinterventions were necessary in 30 patients
      (31%), and coronary artery bypass surgery was performed in 17 patients (18%).
      Event-free survival was 50%. CONCLUSIONS: Excimer laser angioplasty for in-stent
      restenosis was associated with a high incidence of recurrent restenosis in this
      group of patients, suggesting that this technique is unlikely to reduce recurrent
      in-stent restenosis and that other approaches are necessary.

PMID- 10898416
TI  - Occurrence and clinical significance of pseudothrombocytopenia during abciximab
      therapy.
AB  - OBJECTIVES: This study determined the incidence of pseudothrombocytopenia during
      abciximab therapy administered for percutaneous coronary interventions and
      compared the clinical course of patients with pseudothrombocytopenia with the
      clinical courses of patients with thrombocytopenia and patients with normal
      platelet counts. BACKGROUND: Although pseudothrombocytopenia has been previously
      reported during therapy with abciximab, the incidence and significance of this
      occurrence are unknown. The failure to differentiate pseudothrombocytopenia from
      thrombocytopenia could lead to unnecessary interruption of abciximab infusions or
      to platelet transfusions. METHODS: The incidences of pseudothrombocytopenia and
      thrombocytopenia were determined in four large placebo-controlled abciximab
      trials: c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE),
      Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC), Evaluation
      of Percutaneous Transluminal Coronary Angioplasty to Improve Long-term Outcome of
      c7E3 GpIIb/IIIa Receptor Blockade (EPILOG) and Evaluation of Platelet IIb/IIIa
      Inhibitor for Stenting (EPISTENT). The clinical features, bleeding complications
      and major clinical outcomes of patients with pseudothrombocytopenia and those
      with thrombocytopenia were compared with each other and with those of patients
      with normal platelet count. RESULTS: Pseudothrombocytopenia occurred in 2.1% (95%
      confidence intervals [CI]: 1.7%, 2.5%) of abciximab-treated patients and in 0.6%
      of placebo-treated patients (p < 0.001). Thrombocytopenia occurred in 3.7% (95%
      CI: 3.2%, 4.2%) of abciximab-treated patients and in 1.8% (95% CI: 1.3%, 2.3%) of
      placebo-treated patients (p < 0.001). Patients with thrombocytopenia had
      significantly higher rates of major bleeding, major decreases in hemoglobin and
      increased transfusion requirements of both blood and platelets compared with
      those without thrombocytopenia. By contrast, pseudothrombocytopenic patients did
      not differ from patients with normal platelet counts in any of the measures of
      blood loss or transfusion requirements. Thrombocytopenic patients, but not those
      with pseudothrombocytopenia, had increased rates of revascularization at 30 days
      and six months. As previously reported, there was also a higher rate of death and
      myocardial infarction in the thrombocytopenic patients. CONCLUSIONS:
      Pseudothrombocytopenia is the cause of more than one third (36.3%) of low
      platelet counts in patients undergoing coronary interventions who are treated
      with abciximab. This study demonstrates that pseudothrombocytopenia is a benign
      laboratory condition that does not increase bleeding, stroke, transfusion
      requirements or the need for repeat revascularization. It is important to
      recognize pseudothrombocytopenia so that the beneficial effects of abciximab are
      not lost by premature termination of therapy.

PMID- 10898417
TI  - PlA polymorphism of glycoprotein IIIa and risk of adverse events after coronary
      stent placement.
AB  - OBJECTIVE: We designed this prospective study to test the hypothesis that
      platelet antigen (PlA) polymorphism of glycoprotein (GP) IIIa is associated with
      an increased risk for adverse events after coronary stent placement. BACKGROUND:
      Platelets play a central role in arterial thrombosis. The PlA polymorphism of GP
      IIIa, a constituent of the fibrinogen receptor, may influence the platelet
      function and, thereby, the early outcome of patients after coronary stent
      placement. METHODS: The study included 1,759 consecutive patients with stable or
      unstable angina and successful coronary stent placement. Platelet antigen
      genotypes were determined by allele-specific restriction enzyme analysis. The end
      point of the study was a composite of death, myocardial infarction and urgent
      revascularization during the first 30 days after stent placement. RESULTS: The
      PlA1 genotype of the patients included was: 70.2% were homozygous for platelet
      antigen 1 (PlA1), 2.6% homozygous for platelet antigen 2 (PlA1), and 27.2% were
      heterozygous (PlA1/A2). The incidence of the composite end point was 5.5% among
      PlA2 carriers and 5.4% in homozygous PlA1 subjects (p = 0.94). It was 5.4% in
      PlA1/A1 patients, 4.8% in PlA1/A2 patients and 13.0% in PlA2A2 patients (p =
      0.06). The combined incidence of death or myocardial infarction was 4.3% in
      PlA1/A1 patients, 4.2% in PlA1/A2 patients and 13.0% in PlA2/A2 patients (p =
      0.02). CONCLUSIONS: The isolated presence of the PlA2 allele in heterozygous
      patients is not associated with any detectable increase in the risk for an
      adverse 30-day outcome after coronary stenting. This study suggests also that an
      increased risk is likely to be present in homozygous carriers of the PlA2 allele,
      but this should be confirmed in a much larger series of patients.

PMID- 10898418
TI  - PlA2, a variant of GPIIIa implicated in coronary thromboembolic complications.

PMID- 10898419
TI  - Vitamin E supplementation improves endothelial function in type I diabetes
      mellitus: a randomized, placebo-controlled study.
AB  - OBJECTIVES: We sought to determine, in a double-blind, placebo-controlled,
      randomized study, whether vitamin E supplementation (1,000 IU for three months)
      would improve impaired conduit and resistance vessel endothelial vasodilator
      function (EVF) and systemic arterial compliance (SAC) in type I diabetes mellitus
      (DM). BACKGROUND: Oxidative stress is thought to be important in the pathogenesis
      of impaired EVF. Consistent with this hypothesis, we have recently shown that
      impaired EVF is related to low density lipoprotein (LDL) vitamin E content (VEC)
      in young subjects with type 1 DM. METHODS: We assessed EVF in the brachial artery
      (using noninvasive ultrasound, flow-mediated vasodilation [FMD]; n = 41) and in
      the forearm resistance vessels (by flow responses to intrabrachial acetylcholine
      [ACh]; n = 21) and measured SAC (simultaneous aortic blood flow and carotid
      pressure measurements; n = 41) before and after active or placebo therapy.
      RESULTS: The LDL VEC was increased by 127% after supplementation, resulting in a
      significant reduction in the oxidative susceptibility of LDL. There was no time
      dependent change in FMD or in the response to ACh or SAC in the placebo group. A
      significant improvement in FMD (2.6 +/- 0.6% to 7.0 +/- 0.7%, p < 0.005) and the
      dose response to ACh (p < 0.05) were observed in those randomized to vitamin E
      therapy. Systemic arterial compliance was not affected by vitamin E (0.41 +/-
      0.03 vs. 0.49 +/- 0.06 arbitrary compliance units, p = NS). The change in FMD was
      related to the change in LDL VEC (r = 0.42, p < 0.05) and the change in the
      oxidative susceptibility of LDL (r = 0.64, p < 0.0001). CONCLUSIONS: Short-term
      daily oral supplementation with vitamin E improves EVF in both the conduit and
      resistance vessels of young subjects with type I DM.

PMID- 10898420
TI  - Low density lipoprotein cholesterol and coronary microvascular dysfunction in
      hypercholesterolemia.
AB  - OBJECTIVES: The present study evaluates the impact of total cholesterol (TC) and
      its subfractions on coronary flow reserve (CFR), an index of the integrated
      function of the coronary circulation, in asymptomatic subjects. BACKGROUND:
      Endothelial dysfunction of the coronary microcirculation has been reported in
      asymptomatic subjects with hypercholesterolemia. METHODS: Using oxygen-15-labeled
      water and positron emission tomography, myocardial blood flow (MBF, in ml/min per
      g) was measured at rest and during intravenous adenosine (140 microg/kg body
      weight per min) in 80 asymptomatic nonsmoking men: group 1 (n = 61; age 45 +/- 7
      years) had normal TC (< or =6.5 mmol/liter or < or =250 mg/dl) and group 2 (n =
      19; age 48 +/- 10 years) had elevated TC. RESULTS: Total cholesterol were 5.1 +/-
      0.8 and 7.2 +/- 0.7 mmol/liter in groups 1 and 2 (p < 0.0005), respectively; low
      density lipoprotein (LDL) cholesterol levels were 3.2 +/- 0.8 and 4.9 +/- 0.7
      mmol/liter (p < 0.0005); high density lipoprotein (HDL) cholesterol levels were
      1.1 +/- 0.3 and 1.0 +/- 0.4 mmol/liter (p = NS); and triglyceride levels were 1.8
      +/- 1.3 and 3.0 +/- 1.8 mmol/liter (p < 0.005). Groups 1 and 2 did not differ
      with regard to MBF at rest (0.87 +/- 0.14 vs. 0.84 +/- 0.14), MBF during
      adenosine (3.63 +/- 1.02 vs. 3.30 +/- 0.86) or CFR (4.23 +/-1.29 vs. 3.95 +/-
      0.93). A significant but weak correlation was found between CFR and HDL in group
      1 (r = 0.29, p < 0.05), but not in group 2. In contrast, a significant inverse
      correlation between LDL and CFR was found in group 2 (r = -0.61, p < 0.05), but
      not in group 1. CONCLUSIONS: Low density lipoprotein cholesterol but not TC
      correlated inversely with CFR in hypercholesterolemic subjects. Thus, LDL-induced
      coronary microvascular dysfunction could play an important role in the
      pathogenesis of coronary artery disease and its complications.

PMID- 10898422
TI  - Enhanced secretion of cardiac hepatocyte growth factor from an infarct region is
      associated with less severe ventricular enlargement and improved cardiac
      function.
AB  - OBJECTIVES: We hypothesized that the hepatocyte growth factor (HGF) may play a
      cardioprotective role in human myocardial infarction (MI). BACKGROUND: The HGF is
      a novel, multifunctional growth factor implicated in wound healing, angiogenesis
      and promotion of cell survival. Recent animal studies have demonstrated the
      existence of an HGF system in the heart, where it is activated in response to
      myocardial ischemia and reperfusion. METHODS: We studied 40 patients with acute
      myocardial infarction (AMI), who underwent coronary reperfusion therapy upon
      admission. Approximately four weeks later, left ventricular (LV) catheterization
      was repeated to determine the LV ejection fraction (EF), end-diastolic volume
      index (EDVI) and pressure (EDP). The levels of HGF and brain natriuretic peptide
      (BNP) were measured by collecting blood samples from cardiac veins draining the
      infarcted region (MI region) and those draining the noninfarcted region (non-MI
      region). The ratio of the HGF level in the MI region to that in the non-MI region
      (= MI/non-MI ratio) was calculated in each patient as an index of the MI-related
      HGF secretion. The MI/non-MI ratio for BNP was also calculated. RESULTS: The
      MI/non-MI ratio for HGF correlated inversely with LVEDP (r = -0.644, p < 0.0001)
      and LVEDVI (r = -0.843, p < 0.0001) and positively with LVEF (r = 0.763, p <
      0.0001). These correlations were completely opposite in direction from those for
      BNP and LVEDP (r = 0.678, p < 0.0001), LVEDVI (r = 0.783, p < 0.0001) and LVEF (r
      = -0.805, p < 0.0001). These findings indicate that cardiac HGF acts in contrast
      to BNP, a biochemical marker for the development of LV remodeling. CONCLUSIONS:
      Enhanced secretion of cardiac HGF from the MI region is associated with an
      attenuation of ventricular enlargement and an improvement in cardiac function.
      The HGF system may modulate the process of ventricular remodeling and thus have
      important clinical implications.

PMID- 10898421
TI  - Effects of various anticoagulant treatments on von Willebrand factor release in
      unstable angina.
AB  - OBJECTIVES: We tested the hypothesis that different anticoagulant treatments may
      produce different platelet effects and von Willebrand factor (vWf) release in
      unstable angina. BACKGROUND: The early increase of vWf has been reported to be a
      risk factor for adverse outcome in unstable angina. Anticoagulant drugs play a
      key role in stabilization of unstable angina, but they may not have the same
      efficacy and the same effects on acute vWf release. METHODS: We studied 154
      patients enrolled in several clinical trials testing four different anticoagulant
      treatments in unstable angina or non-Q-wave myocardial infarction. Patients were
      treated during at least 48 h by either intravenous unfractionated heparin, one of
      two different low molecular weight heparins (enoxaparin or dalteparin) or the
      direct thrombin inhibitor PEG-hirudin. All patients received aspirin but no
      Ib/IIIa inhibitors. RESULTS: The release of vWf over the first 48 h (delta vWf)
      did not relate to the baseline clinical characteristics. At 30 days of follow-up,
      delta vWf was sevenfold higher in patients with an end point (death, myocardial
      infarction, revascularization) than in patients free of events (+53 +/-7% vs. +7
      +/-14%, p = 0.004). The same trend was present for each component of the
      composite end point with the highest levels for one-month mortality (+87 +/- 32%
      vs. +26 +/- 8%, p = 0.09). The vWf values did not increase over 48 h in patients
      receiving either enoxaparin or PEG-hirudin (+10 +/- 9% and -5 +/- 20%,
      respectively). A serious rise ofvWf was measured in unfractionated heparin
      treated patients (+87 +/- 11%), which differed significantly from the enoxaparin
      group (p = 0.0006) and PEG-hirudin group (p < 0.0001). In dalteparin-treated
      patients, delta vWf was elevated (+48 +/- 8%) and did not differ from the
      unfractionated heparin group (NS). CONCLUSIONS: We confirm that, in unstable
      angina patients, a rise of vWf over the first 48 h is associated with an impaired
      outcome at 30 days. Moreover, the four different anticoagulant treatments tested
      here do not provide the same protection with regards to vWf release, which may
      have important prognostic implications and explain different results observed in
      recent clinical trials.

PMID- 10898424
TI  - Pulse pressure and risk for myocardial infarction and heart failure in the
      elderly.
AB  - OBJECTIVES: We sought to determine whether pulse pressure (PP), a measure of
      arterial stiffness, is an independent predictor of the incidence of coronary
      heart disease (CHD), congestive heart failure (CHF) and overall mortality among
      community-dwelling elderly. BACKGROUND: Current hypertension guidelines classify
      cardiovascular risk on the basis of elevated systolic blood pressure (SBP) or
      diastolic blood pressure (DBP) without considering their combined effects. Recent
      studies suggest that PP is a strong predictor of cardiovascular end points, but
      few data are available among community elderly. METHODS: The study sample
      included 2,152 individuals age > or =65 years, who were participants in the
      Established Populations for Epidemiologic Study of the Elderly program, free of
      CHD and CHF at baseline and still alive at one year after enrollment. Blood
      pressure was measured at baseline. Incidence of CHD, incidence of CHF and total
      mortality were monitored in the following 10 years. RESULTS: There were 328
      incident CHD events, 224 incident CHF events and 1,046 persons who died of any
      cause. Pulse pressure showed a strong and linear relationship with each end
      point. After adjusting for demographics, comorbidity and CHD risk factors, a 10
      mm Hg increment in PP was associated with a 12% increase in CHD risk (95%
      confidence interval [CI], 2% to 22%), a 14% increase in CHF risk (95% CI, 5% to
      24%), and a 6% increase in overall mortality (95% CI, 0% to 12%). While SBP and
      mean arterial pressure (MAP) also showed positive associations with the end
      points, PP yielded the highest likelihood ratio chi-square. When PP was entered
      in the model in conjunction with other blood pressure parameters (SBP, DBP, MAP
      or hypertension stage, respectively), the association remained positive for PP
      but became negative for the other blood pressure variables. The effect of PP
      persisted after adjusting for current medication use and was present in
      normotensive individuals and individuals with isolated systolic hypertension but
      not in individuals with diastolic hypertension. CONCLUSIONS: Elevated PP is a
      powerful independent predictor of cardiovascular end points in the elderly.

PMID- 10898423
TI  - Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin
      mediate leukocyte binding to ischemic heart in humans.
AB  - OBJECTIVES: The expression of endothelial adhesion molecules and their functional
      significance in leukocyte adhesion to human myocardial blood vessels in acute
      myocardial infarction (AMI) were studied. BACKGROUND: Leukocyte extravasation,
      mediated by specific adhesion molecules, exacerbates tissue injury after
      restoration of blood supply to an ischemic tissue. Experimental myocardial
      reperfusion injury can be alleviated with antibodies that block the function of
      adhesion molecules involved in leukocyte emigration, but the relevant molecules
      remain poorly characterized in human AMI. METHODS: Semiquantitative
      immunohistochemistry and in vitro adhesion assays were used to study the
      expression and granulocyte binding abilities of different endothelial adhesion
      molecules in human AMI. Changes in the molecular nature of vascular adhesion
      protein-1 (VAP-1) were evaluated using immunoblotting. RESULTS: Certain
      endothelial adhesion molecules (intercellular adhesion molecule [ICAM-2], CD31
      and CD73) were expressed in myocardial blood vessels homogeneously in normal and
      ischemic hearts, whereas others (E-selectin and peripheral lymph node addressin)
      were completely absent from all specimens. The synthesis of ICAM-1 was locally,
      and that of P-selectin regionally, upregulated in the infarcted hearts when
      compared with nonischemic controls. Vascular adhesion protein-1 showed
      ventricular preponderance in expression and alterations in posttranslational
      modifications during ischemia-reperfusion. Importantly, P-selectin, ICAM-1 and
      VAP-1 mediated granulocyte binding to blood vessels in the ischemic human heart.
      CONCLUSIONS: Human P-selectin, ICAM-1 and VAP-1 appear to be the most promising
      targets when antiadhesive interventions preventing leukocyte-mediated tissue
      destruction after myocardial ischemia are planned.

PMID- 10898425
TI  - Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent
      atrial fibrillation: a randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVES: The primary objective of the present study was to assess the efficacy
      of metoprolol CR/XL to reduce the risk of relapse after cardioversion of
      persistent atrial fibrillation to sinus rhythm. BACKGROUND: Indirect data from
      studies with d,l sotalol provide evidence that the beta-blocking effects of the
      compound are important in maintaining sinus rhythm after cardioversion of atrial
      fibrillation. METHODS: After successful conversion to sinus rhythm, 394 patients
      with a history of persistent atrial fibrillation were randomly assigned to
      treatment with metoprolol CR/XL or placebo. The two treatment groups were similar
      with respect to all pretreatment characteristics. Patients were seen on an
      outpatient basis for recording of resting electrocardiogram (ECG) after one week,
      one, three and six months of follow-up or whenever they felt that they had a
      relapse into atrial fibrillation or experienced an adverse event. RESULTS: In the
      metoprolol CR/XL group, 96 patients (48.7%) had a relapse into atrial
      fibrillation compared with 118 patients (59.9%) in the placebo group (p = 0.005).
      Heart rate in patients after a relapse into atrial fibrillation was significantly
      lower in the metoprolol group (98 +/- 23 beats/min) than in the placebo group
      (107 +/- 27 beats/min). The rate of adverse events reported was similar in both
      groups when the difference in follow-up time was taken into account. CONCLUSIONS:
      The results of this double-blind, placebo-controlled study in patients after
      cardioversion of persistent atrial fibrillation showed that metoprolol CR/XL was
      effective in preventing relapse into atrial fibrillation or flutter.

PMID- 10898426
TI  - beta-blockers for atrial fibrillation: must we consider asymptomatic arrhythmias?

PMID- 10898427
TI  - Increased sympathetic activity after atrioventricular junction ablation in
      patients with chronic atrial fibrillation.
AB  - OBJECTIVES: The aim of this study was to determine the changes in sympathetic
      nerve activity (SNA) after atrioventricular junction (AVJ) ablation in patients
      with chronic atrial fibrillation (AF). BACKGROUND: Polymorphic ventricular
      tachycardia (PMVT) has been reported after AVJ ablation in patients paced at a
      rate of < or =70 beats/min. We hypothesized that AVJ ablation results in
      sympathetic neural changes that favor the occurrence of PMVT and that pacing at
      90 beats/min attenuates these changes. METHODS: Sympathetic nerve activity, 90%
      monophasic cardiac action potential duration (APD90), right ventricular effective
      refractory period (ERP) and blood pressure measurements were obtained in 10
      patients undergoing AVJ ablation. Sympathetic nerve activity was analyzed at
      baseline and during and after successful AVJ ablation for at least 10 min. Data
      were also collected after ablation at pacing rates of 60 and 90 beats/min. The
      APD90 and ERP were measured before and after AV block during pacing at 120
      beats/min. RESULTS: Sympathetic nerve activity increased to 134 +/- 16% of the
      pre-ablation baseline value (p < 0.01) after successful AVJ ablation plus pacing
      at 60 beats/min and decreased to 74 +/- 8% of baseline (p < 0.05) with subsequent
      pacing at 90 beats/min. Both APD90 and ERP increased significantly. CONCLUSIONS:
      1) Ablation of the AVJ followed by pacing at 60 beats/min is associated with an
      increase in SNA. 2) Pacing at 90 beats/min decreases SNA to or below the pre
      ablation baseline value. 3) Cardiac APD and ERP increase after AVJ ablation. The
      increase in SNA, along with the prolongation in APD, may play a role in the
      pathogenesis of ventricular arrhythmias that occur after AVJ ablation.

PMID- 10898428
TI  - Limited posterior left atrial cryoablation in patients with chronic atrial
      fibrillation undergoing valvular heart sugery.
AB  - OBJECTIVES: We sought to evaluate whether a limited surgical cryoablation of the
      posterior region of the left atrium was safe and effective in the cure of atrial
      fibrillation (AF) in patients with associated valvular heart disease. BACKGROUND:
      Extensive surgical ablation of AF is a complex and risky procedure. The posterior
      region of the left atrium seems to be important in the initiation and maintenance
      of AF. METHODS: In 32 patients with chronic AF who underwent heart valve surgery,
      linear cryolesions connecting the four pulmonary veins and the posterior mitral
      annulus were performed. Eighteen patients with AF who underwent valvular surgery
      but refused cryoablation were considered as the control group. RESULTS: Sinus
      rhythm (SR) was restored in 25 (78%) of 32 patients immediately after the
      operation. The cryoablation procedure required 20 +/- 4 min. There were no
      intraoperative and perioperative complications. During the hospital period, one
      patient died of septicemia. Thirty-one patients reached a minimum of nine months
      of follow-up. Two deaths occurred but were unrelated to the procedure. Twenty
      (69%) of 29 patients remained in SR with cryoablation alone, and 26 (90%) of 29
      patients with cryoablation, drugs and radiofrequency ablation. Three (10%) of 29
      patients remained in chronic AF. Right and left atrial contractility was evident
      in 24 (92%) of 26 patients in SR. In control group, two deaths occurred, and SR
      was present in only four (25%) of 16 patients. CONCLUSIONS: Linear cryoablation
      with lesions connecting the four pulmonary veins and the mitral annulus is
      effective in restoration and maintenance of SR in patients with heart valve
      disease and chronic AF. Limited left atrial cryoablation may represent a valid
      alternative to the maze procedure, reducing myocardial ischemic time and risk of
      bleeding.

PMID- 10898429
TI  - Electrical behavior of T-wave polarity alternans in patients with congenital long
      QT syndrome.
AB  - OBJECTIVES: This study was designed to evaluate the incidence and characteristics
      of onset of T-wave polarity alternans (TWPA) in patients with long QT syndrome.
      BACKGROUND: The T-wave alternans is a phenomenon that consists of beat-to-beat
      variability in the amplitude, morphology, and sometimes polarity of the T-wave,
      and it may trigger life-threatening arrhythmias. METHODS: The 24-h Holter
      recordings of 11 patients with congenital long QT syndrome were studied. Episodes
      of TWPA with 10 or more consecutive cycles were selected and analyzed as follows:
      1) mean cycle length (MCL) and QTc interval duration (QTcI) of the episodes of
      TWPA and the 10 cycles preceding and succeeding the TWPA; 2) MCL and QTcI of the
      third, second, and first minute before onset (Mn_3, Mn_2, Mn_1); 3) MCL and QTcI
      from the tenth to the first cycle immediately preceding the onset of TWPA (R_10
      to R_1); 4) MCL and QTcI from the first to the fourteenth cycle during alternans
      (R0 to R14); 5) MCL and QTcI from the first to the tenth cycle immediately
      succeeding TWPA (R+1 to R+10); 6) linear correlation (Lnc) between QT interval
      and cycle length (CL) (LncQT/CL) during alternans and for the 10 preceding
      cycles; 7) Lnc between the first three alternans cycles and episode duration (Lnc
      3CL/EpD); and 8) difference between the longest and shortest QTc interval. We
      also selected episodes consisting of four or more consecutive cycles in order to
      analyze daily rhythms of the phenomenon. RESULTS: The TWPA was observed in 5
      (45%) out of the 11 patients studied. The alternans process is initiated by a
      sudden shortening of the first alternans cycle without previous heart rate
      changes and ends at the moment when prolongation of the cycle tends to occur.
      LncQT/ CL-alternans: r = 0.38 +/- 0.2 (p = 0.20); without alternans: r = 0.81 +/-
      0.06 (p = 0.01). Lnc 3CL/EpD: r = 0.002 (p = 0.992). The QTc difference during
      alternans: 312.0 +/- 52.1 ms; without alternans: 86.0 +/- 36.4 ms (p = 0.001).
      Daily rhythm: 71% of the episodes occurred between 8 AM and 8 PM, with higher
      incidence during the morning. CONCLUSIONS: The TWPA was dependent on the cardiac
      CL; there was loss of the LncQT/CL and an increase in the QT interval
      variability. Like other biological variables, T-wave polarity alternans has a
      higher density during the morning.

PMID- 10898430
TI  - Provocation of neurocardiogenic syncope by clomipramine administration during the
      head-up tilt test in vasovagal syndrome.
AB  - OBJECTIVES: We sought to test the hypothesis that activation of the serotonergic
      system in patients with vasovagal syndrome during the head-up tilt test provokes
      syncope. BACKGROUND: Central serotonergic activation participates in the
      pathogenesis of neurocardiogenic syncope. Drugs increasing serotonin (5-HT) in
      the central nervous system have not been tested as drug challenges during the
      head-up tilt test with clomipramine (Clom-HUT). METHODS: The serotonergic re
      uptake inhibitor clomipramine was infused (5 mg in 5 min) at the start of Clom
      HUT in 55 patients (mean age 40 +/- 17 years) with a positive history of
      recurrent neurocardiogenic syncope and in 22 healthy control subjects (mean age
      46 +/- 15 years). Blood samples were taken at 0, 5, 10 and 20 min for estimation
      of plasma prolactin and cortisol as neuroendocrine indicators of central
      serotonergic responsivity. All subjects had been previously tested with a basic
      60 degrees head-up tilt test (B-HUT) for 30 min, and if negative, isoproterenol
      infusion was given at the end of the test. RESULTS: Twenty-nine (53%) of the 55
      patients and none of the 22 control subjects had a positive result in the B-HUT.
      With Clom-HUT, the proportion of patients who experienced a positive response
      increased to 80% (n = 44), although this happened to only one control subject.
      Prolactin and cortisol plasma levels increased significantly in the positive Clom
      HUT patient group only. CONCLUSIONS: The results indicate an increased
      responsivity of the central serotonergic neural system in subjects with vasovagal
      syndrome, the activation of which leads to sympathetic withdrawal. The use of
      clomipramine infusion with the tilt test seems to considerably improve its
      diagnostic value.

PMID- 10898431
TI  - Tilt methodology in reflex syncope: emerging evidence.

PMID- 10898432
TI  - Misdiagnosis of epilepsy: many seizure-like attacks have a cardiovascular cause.
AB  - OBJECTIVES: We sought to investigate the value of cardiovascular tests to
      diagnose convulsive syncope in patients with apparent treatment-resistant
      epilepsy. BACKGROUND: As many as 20% to 30% of epileptics may have been
      misdiagnosed. Many of these patients may have cardiovascular syncope, with
      abnormal movements due to cerebral hypoxia, which may be difficult to
      differentiate from epilepsy on clinical grounds. METHODS: Seventy-four patients
      (33 men, mean age 38.9 +/- 18 years [range 16 to 77]) who were previously
      diagnosed with epilepsy were studied. Inclusion criteria included continued
      attacks despite adequate anticonvulsant drug treatment (n = 36) or uncertainty
      about the diagnosis of epilepsy, on the basis of the clinical description of the
      seizures (n = 38). Each patient underwent a head-up tilt test and carotid sinus
      massage during continuous electrocardiography, electroencephalography and blood
      pressure monitoring. Ten patients subsequently underwent long-term
      electrocardiographic (ECG) monitoring with an implantable loop recorder. RESULTS:
      In total, an alternative diagnosis was found in 31 patients (41.9%), including 13
      (36.1%) of 36 patients taking an anticonvulsant medication. Nineteen patients
      (25.7%) developed profound hypotension or bradycardia during the head-up tilt
      test, confirming the diagnosis of vasovagal syncope. One other patient had a
      typical vasovagal reaction during intravenous cannulation. Two patients developed
      psychogenic symptoms during the head-up tilt test. Seven patients (9.5%) had
      significant ECG pauses during carotid sinus massage. In two patients, episodes of
      prolonged bradycardia correlated precisely with seizures according to the
      insertable ECG recorder. CONCLUSIONS: A simple, noninvasive cardiovascular
      evaluation may identify an alternative diagnosis in many patients with apparent
      epilepsy and should be considered early in the management of patients with
      convulsive blackouts.

PMID- 10898433
TI  - How the left and right sides of the heart, as well as pulmonary venous drainage,
      adapt to an increasing degree of head-up tilting in hypertrophic cardiomyopathy:
      differences from the normal heart.
AB  - OBJECTIVES: We aimed to assess the differences in the adaptive response of
      patients with hypertrophic cardiomyopathy (HCM) compared with normal subjects, as
      well as any association with increased susceptibility to the test. BACKGROUND:
      Diastolic function contributes importantly in the adaptation of the normal heart
      to head-up tilting. This mechanism may be disturbed by an impaired relaxation in
      HCM. METHODS: Twenty-one male patients with HCM (46 +/- 6 years old) and 22
      healthy men (44 +/- 8 years) were studied using Doppler echocardiography after 1
      and 10 min of head-up tilting at 20 degrees, 40 degrees and 60 degrees. RESULTS:
      In control subjects, tilting was associated with 1) a predominance of diastolic
      pulmonary venous flow and early left ventricular (LV) filling (atrium functioning
      as an open conduit); 2) right ventricular (RV) shrinkage; and 3) no LV
      dimensional variations. In patients with HCM, tilting was associated with 1) a
      prevalence of systolic pulmonary venous flow (atrium functioning as a reservoir
      in which filling depends on atrial relaxation and compliance) and late diastolic
      transmitral flow (atrium working as a booster pump); 2) LV shrinkage; and 3) no
      RV dimension variations. These mechanisms did not prevent stroke volume (SV) from
      decreasing at 40 degrees and 60 degrees in both groups. Because of a lower
      increase in heart rate (HR), a reduction in cardiac output (CO) was greater in
      patients with HCM. The responses were similar after 1 and 10 min of tilting in
      control subjects, whereas in patients, blood pressure (BP), SV and LV dimension
      fell more after 10 min. CONCLUSIONS: Adaptation of the normal heart to tilting is
      based on a ventricular interaction and LV diastolic properties; HCM relies on
      left atrial diastolic and systolic functions. An inadequate HR reaction to a fall
      in BP and SV in HCM (depressed reflexogenic activity) contributes to making CO
      more vulnerable by greater and more prolonged displacements.

PMID- 10898434
TI  - Oxygen uptake efficiency slope: an index of exercise performance and
      cardiopulmonary reserve requiring only submaximal exercise.
AB  - OBJECTIVES: We sought to evaluate, in adults, the efficacy of the Oxygen Uptake
      Efficiency Slope (OUES), an index of cardiopulmonary functional reserve that can
      be based upon a submaximal exercise effort. BACKGROUND: Maximal oxygen uptake
      (VO2,max), the most reliable measure of exercise capacity, is seldom attained in
      standard exercise testing. The OUES, which relates oxygen uptake to total
      ventilation during exercise, was proposed by Baba and coworkers (7) in a study of
      pediatric cardiac patients. They felt this submaximal index of cardiopulmonary
      reserve might be more practical than VO2max and more appropriate than the
      commonly used peak oxygen consumption (VO2 peak). METHODS: Treadmill exercise
      tests with simultaneous respiratory gas measurement were performed in 998 older
      subjects free of clinically recognized cardiovascular disease and 12 male
      patients with congestive heart failure. During incremental exercise, oxygen
      uptake was plotted against the logarithm of total ventilation, and the OUES was
      determined. RESULTS: The OUES, when calculated only from the first 75% of the
      exercise test, differed by 1.9% from the OUES calculated from 100% of exercise
      time in subjects with a peak respiratory exchange rate > or =1.10. On serial
      tests the OUES was less variable than exercise duration or VO2 peak. It
      correlated strongly with VO2max, with forced expiratory volume in 1 s and
      negatively with a history of current smoking. The OUES declined linearly with age
      in both women and men. A small sample of patients with congestive heart failure
      had OUES values much lower than those of older subjects without cardiovascular
      disease. CONCLUSIONS: The OUES is an objective, reproducible measure of
      cardiopulmonary reserve that does not require a maximal exercise effort. It
      integrates cardiovascular, musculoskeletal and respiratory function into a single
      index that is largely influenced by pulmonary dead space ventilation and exercise
      induced lactic acidosis.

PMID- 10898435
TI  - Differential effects of high-frequency versus low-frequency exercise training in
      rehabilitation of patients with coronary artery disease.
AB  - OBJECTIVES: We sought to study the influence of frequency of exercise training
      during cardiac rehabilitation on functional capacity (i.e., peak oxygen
      consumption [VO2] and ventilatory anaerobic threshold [VAT]) and quality of life
      (QoL). BACKGROUND: Although the value of cardiac rehabilitation is now well
      established, the influence of the different program characteristics on outcome
      has received little attention, and the effect of frequency of exercise training
      is unclear. Functional capacity is regularly evaluated by peak VO2 but parameters
      of submaximal exercise capacity such as VAT should also be considered because
      submaximal exercise capacity is especially important in daily living. METHODS:
      Patients with coronary artery disease (n = 130, 114 men; mean age 52 +/- 9 years)
      were randomized to either a high- or low-frequency program of six weeks (10 or 2
      exercise sessions per week of 2 h, respectively). Functional capacity and QoL
      were assessed before and after cardiac rehabilitation. Global costs were also
      compared. RESULTS: Compared with baseline, mean exercise capacity increased in
      both programs: for high- and low-frequency, respectively: peak VO2 = 15% and 12%,
      Wmax = 18% and 12%, VAT = 35% and 12% (all p < 0.001). However, when the programs
      were compared, only VAT increased significantly more during the high-frequency
      program (p = 0.002). During the high-frequency program, QoL increased slightly
      more, and more individuals improved in subjective physical functioning (p =
      0.014). We observed superiority of the high-frequency program, especially in
      younger patients. Mean costs were estimated at 4,455 and 2,273 Euro,
      respectively, for the high- and low-frequency programs. CONCLUSIONS: High
      frequency exercise training is more effective in terms of VAT and QoL, but peak
      VO2 improves equally in both programs. Younger patients seem to benefit more from
      the high-frequency training.

PMID- 10898436
TI  - Elevated circulating levels of serum tumor necrosis factor-alpha in patients with
      hemodynamically significant pressure and volume overload.
AB  - OBJECTIVES: We sought to determine whether serum tumor necrosis factor-alpha (TNF
      alpha) levels are elevated in patients with hemodynamically significant pressure
      and volume overload. BACKGROUND: It has been previously shown that TNF-alpha
      messenger ribonucleic acid (mRNA) and protein are rapidly expressed in the hearts
      of animal models subjected to abrupt hemodynamic overloading. The clinical
      significance of these experimental findings has not been tested in
      pathophysiologically relevant clinical models in human subjects. METHODS: We
      prospectively measured serum TNF-alpha levels and serum TNF receptor 1 and 2
      levels in 21 patients with severe aortic stenosis (AS), in 26 patients with 3+ to
      4+ mitral regurgitation (MR) and in normal age- and gender-matched control
      subjects. Patients with AS and MR were either in New York Heart Association
      (NYHA) functional class I or II and had no significant coronary disease. We
      compared the cytokine levels among the groups using analysis of variance. We
      related cytokine levels to the severity of AS using simple regression analysis.
      RESULTS: Serum TNF-alpha levels in patients with AS (2.1 +/- 1.6 pg/ml, n = 21)
      and MR (1.3 +/-0.7 pg/ml, n = 26) were significantly higher than those in the
      control subjects (0.7 +/-0.2 pg/ml, n = 28). Serum TNF receptor 1 and 2 levels
      were also higher in patients with AS and MR than in control subjects. Cytokine
      levels were higher in patients in NYHA class II than in those in class I. In
      patients with a normal ejection fraction (>50%, n = 16), there was a mild
      positive correlation (r = 0.56, p = 0.025) between serum TNF-alpha levels and the
      mean gradient across the aortic valve. CONCLUSIONS: This study demonstrates that
      serum TNF-alpha is elevated in patients with chronic hemodynamic overloading and
      early cardiac decompensation. Furthermore, these findings suggest not only that
      peripheral TNF-alpha levels correlate with the severity of the hemodynamic
      pressure overload, but also that peripheral TNF-alpha and TNF receptor levels
      increase in direct relation to deteriorating NYHA functional class.

PMID- 10898437
TI  - Baroreceptor dysfunction induced by nitric oxide synthase inhibition in humans.
AB  - OBJECTIVES: We sought to investigate baroreceptor regulation of sympathetic nerve
      activity and hemodynamics after inhibition of nitric oxide (NO) synthesis.
      BACKGROUND: Both the sympathetic nervous system and endothelium-derived
      substances play essential roles in cardiovascular homeostasis and diseases.
      Little is known about their interactions. METHODS: In healthy volunteers, we
      recorded muscle sympathetic nerve activity (MSA) with microneurography and
      central hemodynamics measured at different levels of central venous pressure
      induced by lower body negative pressure. RESULTS: After administration of the NO
      synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 1 mg/kg/min), systolic blood
      pressure increased by 24 mm Hg (p = 0.01) and diastolic blood pressure by 12 mm
      Hg (p = 0.009), while stroke volume index (measured by thermodilution) fell from
      53 to 38 mL/min/m2 (p < 0.002). Administration of L-NMMA prevented the
      compensatory increase of heart rate, but not MSA, to orthostatic stress. The
      altered response of heart rate was not due to higher blood pressure, because
      heart rate responses were not altered during infusion of the alpha-1-adrenoceptor
      agonist phenylephrine (titrated to an equal increase of systolic blood pressure).
      In the presence of equal systolic blood pressure and central venous pressure, we
      found no difference in MSA during phenylephrine and L-NMMA infusion. CONCLUSIONS:
      This study demonstrates a highly specific alteration of baroreceptor regulation
      of heart rate but not muscle sympathetic activity after inhibition of NO
      synthesis in healthy volunteers. This suggests an important role of NO in reflex
      mediated heart rate regulation in humans.

PMID- 10898439
TI  - Echocardiographic findings in fulminant and acute myocarditis.
AB  - OBJECTIVES: We sought to use echocardiography to assess the presentation and
      potential for recovery of left ventricular (LV) function of patients with
      fulminant myocarditis compared with those with acute myocarditis. BACKGROUND: The
      clinical course of patients with myocarditis remains poorly defined. We have
      previously proposed a classification that provides prognostic information in
      myocarditis patients. Fulminant myocarditis causes a distinct onset of illness
      and severe hemodynamic compromise, whereas acute myocarditis has an indistinct
      presentation, less severe hemodynamic compromise and a greater likelihood of
      progression to dilated cardiomyopathy. METHODS: Echocardiography was performed at
      presentation and at six months to test the hypothesis that fulminant (n = 11) or
      acute (n = 43) myocarditis could be distinguished morphologically. RESULTS:
      Patients with both fulminant (fractional shortening 19 +/- 4%) and acute
      myocarditis (17 +/- 7%) had LV systolic dysfunction. Patients with fulminant
      myocarditis had near normal LV diastolic dimensions (5.3 +/- 0.9 cm) but
      increased septal thickness (1.2 +/- 0.2 cm) at presentation, while those with
      acute myocarditis had increased diastolic dimensions (6.1 +/- 0.8 cm, p < 0.01
      vs. fulminant) but normal septal thickness (1.0 +/- 0.1 cm, p = 0.01 vs.
      fulminant). At six months, patients with fulminant myocarditis had dramatic
      improvement in fractional shortening (30 +/- 8%) compared with no improvement in
      patients with acute myocarditis (19 +/- 7%, p < 0.01 for interaction between time
      and type of myocarditis). CONCLUSIONS: Fulminant myocarditis is distinguishable
      from acute myocarditis by echocardiography. Patients with fulminant myocarditis
      exhibit a substantial improvement in ventricular function at six months compared
      with those with acute myocarditis. Echocardiography has value in classifying
      patients with myocarditis and may provide prognostic information.

PMID- 10898438
TI  - Effects of insulin-glucose infusion on left ventricular function at rest and
      during dynamic exercise in healthy subjects and noninsulin dependent diabetic
      patients: a radionuclide ventriculographic study.
AB  - OBJECTIVES: The aim of this study was to evaluate: 1) the effects of insulin
      administration on left ventricular ejection fraction (LVEF) during exercise, and
      2) the eventual impairment of the cardiovascular response to insulin in
      noninsulin dependent diabetes mellitus. BACKGROUND: Insulin influences the
      cardiovascular system, but its effect on left ventricular function has yet to be
      established. METHODS: The effects of normal saline (test A) and insulin-glucose
      (insulin = 1.7 mU x kg(-1) x min(-1); glucose = 6 mg x kg(-1)min(-1)) (test B)
      infusions on systolic and diastolic functions at rest and during dynamic exercise
      were examined by radionuclide ventriculography. Twenty-two noninsulin-dependent
      diabetic patients and 22 gender, age and body mass index matched healthy subjects
      were investigated. RESULTS: Both groups had normal scintigraphic parameters at
      rest and during dynamic exercise. Rest- and stress-LVEF as well as rest- and
      stress-peak filling rate were significantly (p < 0.001) lower in diabetic than in
      healthy subjects, both in test A and B. Rest-LVEF was significantly higher during
      test B than it was in test A only in diabetic subjects (p < 0.01). Stress-LVEF
      was significantly higher (p < 0.05) during test B than it was in test A, in both
      groups. Insulin-glucose infusion did not modify rest- and stress-peak filling
      rate in either group. No difference in left ventricular end diastolic volume and
      in mean blood pressure was found between test A and B at rest and during exercise
      in either group. A significant linear correlation between LVEF and the index of
      insulin sensitivity was found in diabetic patients. CONCLUSIONS: In both normal
      and diabetic humans, insulin induces a very important rise in LVEF after
      submaximal work. However, the rise is significantly lower in diabetic than in
      nondiabetic subjects. The increase in exercise-LVEF on insulin is likely due to
      an enhancement of ventricular contractility. Insulin resistance could justify the
      lower angioscintigraphic indexes in diabetic subjects.

PMID- 10898440
TI  - Is myocardial Na+/Ca2+ exchanger transcription a marker for different stages of
      myocardial dysfunction? Quantitative polymerase chain reaction of the messenger
      RNA in endomyocardial biopsies of patients with heart failure.
AB  - OBJECTIVES: This study was designed to determine the stage of myocardial
      dysfunction at which an upregulation of the Na+/Ca2+ exchanger (EXCH)
      transcription takes place. BACKGROUND: Because EXCH is an important regulator of
      intracellular calcium homeostasis, alterations in EXCH expression may occur
      before the onset of end-stage heart failure (HF) to maintain normal intracellular
      Ca2+ concentrations. We analyzed whether the EXCH transcription level is
      correlated to the degree of myocardial dysfunction and whether it can be a
      suitable molecular marker to define the transition to myocardial decompensation
      early on. METHODS: By quantitative polymerase chain reaction technique, the level
      of EXCH transcription was analyzed in myocardial biopsies from 40 patients with
      various degrees of myocardial dysfunction due to valvular heart disease (VHD; n =
      22) or dilated cardiomyopathy (DCM; n = 18). Additionally, biopsies from 7
      individuals with excluded heart disease and explanted heart tissue from 13
      patients with end-stage HF were investigated. RESULTS: The level of EXCH
      transcription of controls (2.6 +/- 1.2 attomoles [amol]/ng total RNA) did not
      differ from that of patients with DCM (2.3 +/- 1.5 amol/ng) or VHD (2.1 +/- 1.5
      amol/ng). No alteration in the EXCH transcription was found in VHD and DCM
      patients with respect to the severity of myocardial dysfunction. However,
      patients with end-stage HF showed a four-fold increase in EXCH transcription,
      amounting to 8.9 +/- 1.9 amol/ng (p < 0.05). CONCLUSIONS: The upregulation in
      EXCH transcription either occurs very late in human heart failure or is a
      phenomenon of heart transplantation in end-stage HF. Consequently, myocardial
      EXCH transcription cannot be used as a marker for early myocardial
      decompensation.

PMID- 10898441
TI  - End-tidal CO2 pressure decreases during exercise in cardiac patients: association
      with severity of heart failure and cardiac output reserve.
AB  - OBJECTIVES: We measured end-tidal CO2 pressure (PETCO2) during exercise and
      investigated the relationship between PETCO2 and exercise capacity, ventilatory
      parameters and cardiac output to determine the mechanism(s) of changes in this
      parameter. BACKGROUND: It is unclear whether PETCO2 is abnormal at rest and
      during exercise in cardiac patients. METHODS: Cardiac patients (n = 112) and
      normal individuals (n = 29) performed exercise tests with breath-by-breath gas
      analysis, and measurement of cardiac output and arterial blood gases. RESULTS:
      PETCO2 was lower in patients than in normal subjects at rest and decreased as the
      New York Heart Association class increased, whereas the partial pressure of
      arterial CO2 did not differ among groups. Although PETCO2 increased during
      exercise in patients, it remained lower than in normal subjects. PETCO2 in
      relation to cardiac output was similar in patients and normal subjects. PETCO2 at
      the respiratory compensation point was positively correlated with the O2 uptake
      (r = 0.583, p < 0.0001) and the cardiac index at peak exercise (r = 0.582, p <
      0.0001), and was negatively correlated with the ratio of physiological dead space
      to the tidal volume. The sensitivity and specificity of PETCO2 to predict an
      inadequate cardiac output were 76.6% and 75%, respectively, when PETCO2 at
      respiratory compensation point and a cardiac index at peak exercise that were
      less than the respective control mean-2 SD values were considered to be abnormal.
      CONCLUSIONS: PETCO2 was below normal in cardiac patients at rest and during
      exercise. PETCO2 was correlated with exercise capacity and cardiac output during
      exercise, and the sensitivity and specificity of PETCO2 regarding decreased
      cardiac output were good. PETCO2 may be a new ventilatory abnormality marker that
      reflects impaired cardiac output response to exercise in cardiac patients
      diagnosed with heart failure.

PMID- 10898442
TI  - The medium-term findings in coronary arteries by intravascular ultrasound in
      infants and children after heart transplantation.
AB  - OBJECTIVES: The study purposes were to determine 1) whether intravascular
      ultrasound (IVUS) was more sensitive than angiography for the detection of post
      transplant coronary artery disease (PTCAD) in pediatric patients; and 2) whether
      those transplanted as neonates reacted differently than older patients.
      BACKGROUND: Experience with IVUS for the diagnosis of PTCAD in children is
      limited. METHODS: Patients were divided into two groups: those transplanted as
      neonates (early group) and those transplanted in infancy or childhood (late
      group). Morphometric analysis was performed, including maximal intimal thickness
      (MIT) and intimal index (II). Stanford classification was used to grade lesion
      severity. Acute rejection and cytomegalovirus (CMV) status were correlated with
      MIT and II. RESULTS: Thirty children were studied (early group, n = 13; late
      group, n = 17). All segments studied were angiographically normal. Mean MIT and
      mean II were significantly greater in the late group (0.26 +/- 0.14 vs. 0.13 +/-
      0.04 mm, p < 0.001 and 0.11 +/- 0.07 vs. 0.07 +/- 0.03 mm, p = 0.04,
      respectively). There was a significant correlation between MIT and II in those
      who had acute rejection in the late group. Patients in the late group who were
      CMV-positive had a significantly higher MIT compared with those in the late group
      with negative serology (p = 0.04). CONCLUSIONS: Intravascular ultrasound was more
      sensitive than angiography in detecting PTCAD after pediatric heart
      transplantation. There is a possible role for acute rejection and CMV in the
      development of PTCAD.

PMID- 10898443
TI  - Long-term outcome in congenitally corrected transposition of the great arteries:
      a multi-institutional study.
AB  - OBJECTIVES: The purpose of this study was to determine long-term outcome in
      adults with congenitally corrected transposition of the great arteries (CCTGA),
      with particular emphasis on systemic ventricular dysfunction and congestive heart
      failure (CHF). BACKGROUND: Patients with CCTGA have the anatomical right
      ventricle as their systemic pumping chamber, with ventricular dysfunction and CHF
      being relatively common in older adults. METHODS: Retrospective analysis of
      records of 182 patients from 19 institutions were reviewed to determine current
      status and possible risk factors for systemic ventricular dysfunction and CHF.
      Factors considered included age, gender, associated cardiac defects, operative
      history, heart block, arrhythmias and tricuspid (i.e., systemic atrioventricular)
      regurgitation (TR). RESULTS: Both CHF and systemic ventricular dysfunction were
      common in groups with or without associated cardiac lesions. By age 45, 67% of
      patients with associated lesions had CHF, and 25% of patients without associated
      lesions had this complication. The rates of systemic ventricular dysfunction and
      CHF were higher with increasing age, the presence of significant associated
      cardiac lesions, history of arrhythmia, pacemaker implantation, prior surgery of
      any type, and particularly with tricuspid valvuloplasty or replacement. Aortic
      regurgitation (a previously unreported problem) was also relatively common in
      this patient population. CONCLUSIONS: Patients with CCTGA are increasingly
      subject to CHF with advancing age; this complication is extremely common by the
      fourth and fifth decades. Tricuspid (systemic atrioventricular) valvular
      regurgitation is strongly associated with RV (anatomical right ventricle
      connected to aorta in CCTGA patients; systemic ventricle in CCTGA) dysfunction
      and CHF; whether it is causative or a secondary complication remains speculative.

PMID- 10898444
TI  - Isolated ductus arteriosus aneurysm in the fetus and infant: a multi
      institutional experience.
AB  - OBJECTIVES: The purpose of this study was to describe the clinical
      characteristics and outcome and to elucidate the pathogenesis of ductus
      arteriosus aneurysm (DAA). BACKGROUND: Ductus arteriosus aneurysm is a rare
      lesion that can be associated with severe complications including
      thromboembolism, rupture and death. METHOD: We reviewed the clinical records,
      diagnostic imaging studies and available histology of 24 cases of DAA, diagnosed
      postnatally (PD) in 15 and antenatally (AD) in 9 encountered in five
      institutions. RESULTS: Of PD cases, 13 presented at <2 months, and all AD cases
      were detected incidentally after 33 weeks of gestation during a late trimester
      fetal ultrasound study. Of the 24, only 4 had DAA-related symptoms and 6 had
      associated syndromes: Marfan, Smith-Lemli-Opitz, trisomies 21 and 13 and one
      possible Ehlers-Danlos. Three had complications related to the DAA: thrombus
      extension into the pulmonary artery, spontaneous rupture, and asymptomatic
      cerebral infarction. Six underwent uncomplicated DAA resection for ductal
      patency, DAA size or extension of thrombus. In the four examined, there was
      histologic evidence of reduced intimal cushions in two and abnormal elastin
      expression in two. Five of the 24 died, with only one death due to DAA. Of 19
      survivors, all but one remain clinically asymptomatic at a median follow-up of 35
      months; however, two have developed other cardiac lesions that suggest Marfan
      syndrome. A review of 200 consecutive third trimester fetal ultrasounds suggests
      an incidence of DAA of 1.5%. CONCLUSIONS: Ductus arteriosus aneurysm likely
      develops in the third trimester perhaps due to abnormal intimal cushion formation
      or elastin expression. Although it can be associated with syndromes and severe
      complications, many affected infants have a benign course. Given the potential
      for development of other cardiac lesions associated with connective tissue
      disease, follow-up is warranted.

PMID- 10898445
TI  - Long-term effect of angiotensin-converting enzyme inhibitor in volume overloaded
      heart during growth: a controlled pilot study.
AB  - OBJECTIVES: This study examined whether long-term therapy with an angiotensin
      converting enzyme (ACE) inhibitor reduces excessive increases in left ventricular
      (LV) mass as well as volume in growing children with aortic regurgitation or
      mitral regurgitation. BACKGROUND: The ACE inhibitor reduces volume overload and
      LV hypertrophy in adults with aortic or mitral regurgitation. METHODS: This study
      included 24 patients whose ages ranged from 0.3 to 16 years at entry to the
      study. On echocardiography, we measured LV size, systolic function and mass.
      After obtaining baseline data, patients were allocated into two groups. Twelve
      patients were given an ACE inhibitor (ACE inhibitor group), and 12 patients were
      not (control group). Echo parameters were again assessed after an average 3.4
      years of follow-up. RESULTS: Left ventricular parameters at baseline in the two
      groups were similar. The Z value of LV end-diastolic dimensions decreased from
      +0.82 +/- 0.55 to +0.57 +/- 0.58 in the ACE inhibitor group, whereas it increased
      from +0.73 +/- 0.85 to +1.14 +/- 1.04 in the control group (mean change -0.25 +/-
      0.33 for the ACE inhibitor group vs. +0.42 +/- 0.48 for the control group, p =
      0.0007). The mass normalized to growth also reduced from 221 +/- 93% to 149 +/-
      44% of normal in the ACE inhibitor group and increased from 167 +/- 46% to 204 +/
      59% of normal in the control group (mean change -72 +/- 89% of normal for the ACE
      inhibitor group vs. +37 +/- 35% of normal for the control group, p = 0.0007).
      CONCLUSIONS: Long-term treatment with ACE inhibitors is effective in reducing not
      only LV volume overload but also LV hypertrophy in the hearts of growing children
      with LV volume overload.

PMID- 10898446
TI  - Effect of carvedilol in comparison with metoprolol on myocardial collagen
      postinfarction.
AB  - OBJECTIVES: We sought to compare the effects of two different beta-blockers,
      carvedilol and metoprolol, to an angiotensin-converting enzyme (ACE) inhibitor
      (captopril) on myocardial collagen deposition during healing and ventricular
      remodeling after myocardial infarction (MI). BACKGROUND: Beta-adrenergic blockade
      has been shown to be beneficial post-MI and in chronic heart failure. Carvedilol
      is a new-generation vasodilating beta-blocker with additional alpha1-adrenoceptor
      antagonism and an antiproliferative action, but it is not known if it is more
      beneficial than standard selective beta-blockers. METHODS: Using a rat model of
      MI, induced by left coronary ligation, we studied the effects of 11 weeks of
      therapy with oral carvedilol, metoprolol or captopril on hemodynamics, tissue
      weights, collagen volume fraction and hydroxyproline content. RESULTS: Both beta
      blockers caused similar decreases in heart rate and LVEDP compared with untreated
      post-MI rats. At equivalent beta-adrenoceptor blocking doses, however,
      carvedilol, but not metoprolol, attenuated the increase in collagen content in
      noninfarcted regions and prevented the increase in right ventricular weight/body
      weight (all p < 0.05), and its effect was similar to captopril. Metoprolol
      treatment tended to increase right ventricular weight and heart weight (p <
      0.05). There were no differences in infarct size between the groups. CONCLUSIONS:
      Long-term treatment with both beta-blockers, as well as an ACE inhibitor,
      benefited the healing process in rats post-MI. At equivalent myocardial beta
      adrenoceptor blocking doses, however, carvedilol significantly reduced myocardial
      collagen in the noninfarcted myocardium and cardiac hypertrophy in the right
      ventricle, whereas metoprolol had no effect on myocardial collagen deposition.

PMID- 10898447
TI  - Signaling and expression for mitochondrial membrane proteins during left
      ventricular remodeling and contractile failure after myocardial infarction.
AB  - OBJECTIVES: This study was conducted to test hypotheses stating that: 1) altered
      signaling for mitochondrial membrane proteins occurs during postinfarction
      remodeling, and 2) successful myocardial adaptation relates to promotion of
      specific mitochondrial membrane components. BACKGROUND: Abnormalities in high
      energy phosphate content and limitations in adenosine 5'-triphosphate (ATP)
      synthesis rate occur during the transition to contractile failure from
      compensatory remodeling after left ventricular infarction. The adenine nucleotide
      translocator (ANT) and F1-ATPase respectively regulate mitochondrial adenosine 5'
      diphosphate (ADP)/ATP exchange and ADP-phosphorylation, which are key components
      of high-energy phosphate metabolism. METHODS: Steady-state mRNA and protein
      expression for ANT isoform1 and the beta subunit of the F1-ATPase (betaF1) were
      analyzed in myocardium remote from the infarction zone eight weeks after left
      circumflex coronary artery ligation in pigs, demonstrating either successful left
      ventricular remodeling (LVR, n = 8) or congestive heart failure (CHF, n = 4) as
      determined by clinical and contractile performance parameters. RESULTS:
      Substantial reductions in steady-state mRNA expression for ANT1 and betaF1
      relative to normal (n = 8) occur in CHF, p < 0.01, but not in LVR. Relative
      expression for both proteins coordinated with their respective steady-state mRNA
      levels; CHF at 40% normal, p < 0.05 for ANT and 70% normal for betaF1, p < 0.05.
      CONCLUSIONS: Maintained signaling for major mitochondrial membrane proteins
      occurs in association with successful remodeling and adaptation after infarction.
      Reduced expression of these proteins relates to limited ATP synthesis capacity
      and high energy phosphate kinetic abnormalities previously demonstrated in CHF.
      These findings imply that mitochondrial processes participate in myocardial
      remodeling after infarction.

PMID- 10898449
TI  - The fellowship match selection process: where has collegiality gone?

PMID- 10898448
TI  - 8-chloro-cAMP inhibits smooth muscle cell proliferation in vitro and neointima
      formation induced by balloon injury in vivo.
AB  - OBJECTIVES: The aims of the present study were to assess 1) the effect of 8-C1
      cAMP (cyclic-3'-5'-adenosine monophosphate) on vascular smooth muscle cell (VSMC)
      proliferation in vitro and 2) the efficacy of systemic administration of 8-C1
      cAMP on neointimal formation after balloon injury in vivo. BACKGROUND: Neointimal
      formation after vascular injury is responsible for restenosis after arterial
      stenting. Recently, 8-C1-cAMP, a cAMP analogue that induces growth arrest, has
      been safely administered in phase I studies in humans. METHODS: The effect of 8
      C1-cAMP on cell proliferation was first assessed on SMCs in vitro. To study the
      effects of cAMP in vivo, balloon injury was performed in 67 rats using a 2F
      Fogarty balloon catheter. RESULTS: The 8-C1-cAMP markedly inhibited VSMC
      proliferation in vitro, reduced protein kinase A (PKA) RIalpha subunit
      expression, and induced PKA RIIbeta subunit expression. In addition, 8-C1-cAMP
      reduced, in a dose-dependent manner, neointimal area and neointima/media ratio
      after balloon injury. The proliferative activity, assessed by proliferating
      nuclear cell antigen immunostaining, revealed a reduction of proliferative
      activity of VSMCs in vivo in the 8-C1-cAMP group. Moreover, the systemic
      administration of 8-C1-cAMP did not affect renal function, blood pressure and
      heart rate. CONCLUSIONS: We conclude that 8-C1-cAMP potently inhibits VSMC
      proliferation in vitro and reduces neointima formation by balloon injury in vivo
      after systemic administration. These data may have a clinical relevance in
      designing future strategies to prevent restenosis after arterial stenting and
      perhaps after percutaneous transluminal coronary angioplasty.

PMID- 10898450
TI  - Presient's page: the human genome project: implications for cardiologists and
      their patients.

PMID- 10898452
TI  - Nonocclusive coronary dissections: to stent or not to stent?

PMID- 10898451
TI  - Angioplasty for acute myocardial infarction in community hospital without
      surgical back-up: response to Wharton and Angelini publications "should
      guidelines be changed?: not whether but when".

PMID- 10898453
TI  - Coenzyme Q10 as an adjunctive therapy in patients with congestive heart failure.

PMID- 10898454
TI  - Renal effect of low-dose dopamine in high-risk patients undergoing coronary
      angiography.

PMID- 10898456
TI  - Explaining the race paradox of coronary calcium prevalence and survival.

PMID- 10898455
TI  - Extraction efficiency of extracellular MRI contrast agents and its model
      dependent effects on estimates of myocardial blood flow.

PMID- 10898457
TI  - Results from late-breaking clinical trials sessions at ACCIS 2000 and ACC 2000.
      American College of Cardiology.

PMID- 10898458
TI  - American College of Cardiology/American Heart Association Expert Consensus
      Document on electron-beam computed tomography for the diagnosis and prognosis of
      coronary artery disease.

PMID- 10898459
TI  - Histamine fish poisoning revisited.
AB  - Histamine (or scombroid) fish poisoning (HFP) is reviewed in a risk-assessment
      framework in an attempt to arrive at an informed characterisation of risk.
      Histamine is the main toxin involved in HFP, but the disease is not uncomplicated
      histamine poisoning. Although it is generally associated with high levels of
      histamine (> or =50 mg/100 g) in bacterially contaminated fish of particular
      species, the pathogenesis of HFP has not been clearly elucidated. Various
      hypotheses have been put forward to explain why histamine consumed in spoiled
      fish is more toxic than pure histamine taken orally, but none has proved totally
      satisfactory. Urocanic acid, like histamine, an imidazole compound derived from
      histidine in spoiling fish, may be the "missing factor" in HFP. cis-Urocanic acid
      has recently been recognised as a mast cell degranulator, and endogenous
      histamine from mast cell degranulation may augment the exogenous histamine
      consumed in spoiled fish. HFP is a mild disease, but is important in relation to
      food safety and international trade. Consumers are becoming more demanding, and
      litigation following food poisoning incidents is becoming more common. Producers,
      distributors and restaurants are increasingly held liable for the quality of the
      products they handle and sell. Many countries have set guidelines for maximum
      permitted levels of histamine in fish. However, histamine concentrations within a
      spoiled fish are extremely variable, as is the threshold toxic dose. Until the
      identity, levels and potency of possible potentiators and/or mast-cell
      degranulating factors are elucidated, it is difficult to establish regulatory
      limits for histamine in foods on the basis of potential health hazard. Histidine
      decarboxylating bacteria produce histamine from free histidine in spoiling fish.
      Although some are present in the normal microbial flora of live fish, most seem
      to be derived from post-catching contamination on board fishing vessels, at the
      processing plant or in the distribution system, or in restaurants or homes. The
      key to keeping bacterial numbers and histamine levels low is the rapid cooling of
      fish after catching and the maintenance of adequate refrigeration during handling
      and storage. Despite the huge expansion in trade in recent years, great progress
      has been made in ensuring the quality and safety of fish products. This is
      largely the result of the introduction of international standards of food hygiene
      and the application of risk analysis and hazard analysis and critical control
      point (HACCP) principles.

PMID- 10898460
TI  - Hygiene aspects of modern poultry chilling.
AB  - An evaluation was made of six commercial poultry chilling systems in relation to
      factors affecting microbial-contamination of carcasses. These systems included
      water immersion chilling, air chilling and air chilling with evaporative cooling
      using water sprays. Samples of neck skin and body cavity were taken from
      carcasses, together with samples from the chilling environment. These were
      examined for total aerobic mesophilic microbes and counts of presumptive coliform
      bacteria and Pseudomonas spp. at specific points in the chilling process.
      Physical measurements included surface and deep-muscle temperatures of carcasses,
      water temperatures and chlorine concentrations in the immersion system and air
      speed and temperature during air chilling. The results obtained for water
      immersion chilling confirmed previous experience that the washing effect reduces
      microbial contamination of carcasses, although initially the numbers of
      pseudomonads tended to increase. The air chillers varied in design and mode of
      operation, but had little overall effect on microbial contamination of the skin.
      When a completely dry process was used, microbial numbers were reduced
      approximately ten-fold in the body cavity. However, the use of water sprays
      tended to increase contamination of the cavity, while relatively heavy spraying
      using non-chlorinated water, resulted in a substantial increase in the numbers of
      pseudomonads.

PMID- 10898461
TI  - Probability of detection of Salmonella using different analytical procedures,
      with emphasis on subspecies diarizonae serovar 61:k:1,5,(7) [S. IIIb
      61:k:1,5,(7)].
AB  - A parameter for assessing qualitative methods is suggested: 'The probability of
      detection' has been used in this study to compare the efficiency of commonly used
      media for detecting Salmonella in mutton and faeces. Mutton and ovine faeces
      spiked with strains of Salmonella IIIb 61:k: 1,5,(7) and Salmonella Typhimurium
      were analysed and the performance of each combination of media was estimated.
      Extensive variation between serovars and strains of identical serovars were
      recorded. In meat, an inoculum of up to 10(6)/g was needed to detect salmonellae
      with 90% probability, while in faeces even 10(7)/g was not enough for some
      strains of S. IIIb 61:k:1,5,(7). All method combinations thus had a rather low
      efficiency. Based on our experiments, we recommend using a combination of the XLD
      medium and any of the three selective broths for detection of S. IIIb
      61:k:1,5,(7) from mutton, while we recommend using the SC broth with any of the
      three plating media for detection from ovine faeces.

PMID- 10898462
TI  - Karyotype of Penicillium nalgiovense and assignment of the penicillin
      biosynthetic genes to chromosome IV.
AB  - The karyotype of Penicillium nalgiovense was determined by pulsed-field gel
      electrophoresis and compared to the karyotype of P. chrysogenum. Both species
      have four chromosomes, but they differ in the size of the chromosomes and in the
      overall size of the genome. The sizes of the P. nalgiovense chromosomes as
      determined by pulsed-field gel electrophoresis are: 9.1 Mb, 7.9 Mb, 5.4 Mb and
      4.1 Mb which gives in summary a genome size of 26.5 Mb. This compares to 34.1 Mb
      for P. chrysogenum. The penicillin gene cluster was located by Southern
      hybridization on chromosome IV, the smallest chromosome of P. nalgiovense
      compared to chromosome 1, the largest chromosome of P. chrysogenum.

PMID- 10898463
TI  - Evaluation of the hygienic performances of the processes for cleaning, dressing
      and cooling pig carcasses at eight packing plants.
AB  - The hygienic performances of the processes for the production of cooled carcasses
      at eight pork packing plants were assessed from small sets of microbiological
      data. At each plant, a single sample was obtained from a randomly selected site
      on each of 25 randomly selected carcasses at each of three stages of processing,
      which were after polishing, after washing at the end of the dressing process, and
      after cooling. The aerobic bacteria, coliforms and Escherichia coli recovered
      from each sample were enumerated. When bacteria of one type were recovered from >
      or = 20 of 25 samples, the log mean number of those bacteria on the population of
      carcasses undergoing processing was estimated on the assumption that the set of
      counts was normally distributed. The log of the total number recovered from 25
      samples was calculated for each set of counts. The log mean numbers of total
      aerobic bacteria recovered from the polished carcasses at different plants ranged
      from about 1.9 to 3.8 log cfu cm(-2). At six of the plants, the log mean numbers
      of total aerobes on the cooled carcasses did not differ substantially from the
      log mean numbers on the polished carcasses, but the log mean numbers on the
      cooled carcasses were substantially higher at one plant and substantially lower
      at another than on the polished carcasses. Coliforms and E. coli were recovered
      from too few samples in most sets from cooled carcasses for estimation of their
      log mean numbers. However, the log total numbers of coliforms and E. coli
      recovered indicated that substantial numbers of those organisms were added to
      carcasses during the dressing processes at four of the plants, and that the
      numbers on the carcasses were substantially reduced by the processes for cooling
      without spraying at two of the plants. At seven of the plants, the total numbers
      of coliforms and E. coli recovered from cooled carcasses were <3.1 and <2.2 log
      cfu 2500 cm(-2), respectively. The findings indicate that production processes
      for pig carcasses can be operated to give cooled carcasses with log mean numbers
      of total aerobes < 2 cm(-2), and log total numbers of coliforms and E. coli each
      < 1 2500 cm(-2).

PMID- 10898464
TI  - Efficacy of novel organic acid and hypochlorite treatments for eliminating
      Escherichia coli O157:H7 from alfalfa seeds prior to sprouting.
AB  - This study investigated novel two-step organic acid/hypochlorite treatments as
      alternatives to 20000 ppm active chlorine (from calcium hypochlorite) for
      eliminating Escherichia coli O157:H7 from alfalfa seeds prior to sprouting.
      Commercially available alfalfa seeds were inoculated with a five-strain E. coli
      O157:H7 mixture and dried to attain ca. 10(6) CFU/g of seeds. Seeds then
      underwent one of several soak treatments including: (1) 5% (v/v) lactic acid for
      10 min at 42 degrees C; (2) 5% acetic acid (v/v) for 10 min at 42 degrees C; (3)
      2.5% lactic acid for 10 min at 42 degrees C followed by 2000 ppm active chlorine
      (from calcium hypochlorite) for 15 min at 25 degrees C; (4) 5% lactic acid for 10
      min at 42 degrees C followed by 2000 ppm active chlorine for 15 min at 25 degrees
      C; or (5) 20000 ppm active chlorine for 15 min at 25 degrees C. Each treatment
      reduced numbers of inoculum cells by about 6.0 log10 CFU/g as determined by
      plating on Sorbitol MacConkey agar (SMac). Plating on non-selective brain heart
      infusion agar (BHI) showed that treatments 1-4 reduced counts by 2.3-4.1 log10
      CFU/g, thus indicating a large proportion of injured cells. Successive lactic
      acid and hypochlorite treatments (3 and 4) were more lethal than either organic
      acid alone (1 and 2). No surviving cells were detected on SMac or BHI following
      treatment with 20000 ppm active chlorine (treatment 5). Regardless of the
      previous treatment, E. coli O157:H7 counts increased to 10(7)-10(8) CFU/g during
      sprouting. Germination of seeds was not adversely affected by any of the
      treatments (germination > 90%). Results of this study show that: (a) non-lethal
      cell injury must be considered when evaluating intervention treatments against E.
      coli O157:H7 on alfalfa seeds; (b) reductions of 2-4 log10 CFU/g can be attained
      without using 20000 ppm active chlorine; (c) successive lactic acid and
      hypochlorite treatments have greater lethality than organic acid treatments
      alone; and (d) none of the treatments tested can prevent regrowth of surviving E.
      coli O157:H7 during sprouting.

PMID- 10898465
TI  - Biological control of blue mould on apple by a strain of Candida sake under
      several controlled atmosphere conditions.
AB  - The biocontrol potential of the yeast Candida sake (CPA-1) against Penicillium
      expansum decay of apples under several controlled atmosphere conditions was
      investigated. In a laboratory trial under different commercial cold storage
      conditions, increasing concentrations of C. sake improved decay control. A
      maximum reduction of decay was achieved at 3% O2-3% CO2 atmosphere. It amounted
      to a 97% lesion reduction after treatment with a suspension containing 2.4 x
      10(6) CFU/ml of C. sake (CPA-1). In a semi-commercial trial at 1 degree C with
      wounded fruits, the reduction in decay diameter caused by C. sake exceeded 80%
      after 60 days at 21% O2 and 60% after 120 days of storage under controlled
      atmosphere conditions. For seven controlled atmosphere conditions studied, a
      significant influence by C. sake on the P. expansum decay was observed, and the
      lesion size was reduced more than 70% by C. sake at 10(7) CFU/ml. The populations
      of C. sake (CPA-1) on the apple surface followed the same pattern under all
      controlled atmosphere conditions studied. They decreased 4-10-fold during the
      first 2 weeks, followed by an increase to the initial level after 45 days, and
      thereafter the count remained constant for the period of 90 days examined. This
      indicated the capacity of C. sake (CPA-1) to colonize the surface of apples under
      various storage conditions. The ability to colonize was even higher in apple
      wounds.

PMID- 10898466
TI  - Shelf life of modified atmosphere packed cooked meat products: addition of Na
      lactate as a fourth shelf life determinative factor in a model and product
      validation.
AB  - Cooked meat products are often post-contaminated because of a packaging and/or
      slicing step after the pasteurisation process. The shelf life is therefore
      limited and can be extended by adding Na-lactate. A previously developed model
      for the spoilage of gas packed cooked meat products, including temperature, water
      activity and dissolved CO2 as independent variables, was extended with a fourth
      factor: the Na-lactate concentration in the aqueous phase of the meat product.
      Models were developed for the maximum specific growth rate mu(max) and the lag
      phase lambda of the specific spoilage organism Lactobacillus sake subsp.
      carnosum. Quadratic response surface equations were compared with extended
      Ratkowsky models. In general, response surface equations fitted the experimental
      data best but in the case of mu(max) the response surface model predicted
      illogical growth behaviour at low water activities and high Na-lactate
      concentrations. A extensive product validation of the mathematical models was
      performed by means of inoculated as well as naturally contaminated industrially
      prepared cooked meat products. The deviations of the experimentally determined
      versus predicted growth parameters in inoculated cooked meat products were in
      general small. Both types of models were also able to predict the shelf life of
      naturally contaminated cooked meat products, except for pate where an under
      estimation of the shelf life was predicted by the response surface equations. The
      validation studies revealed higher accuracy of the extended Ratkowsky models in
      comparison to the response surface equations. A significant shelf life extending
      effect of Na-lactate was predicted, which was more pronounced at low refrigerated
      temperatures. A synergistic effect has also been noticed between Na-lactate and
      carbon dioxide which, at least partly, could be explained by the pH-decreasing
      effect of CO2.

PMID- 10898467
TI  - Analysis of Salmonella serotypes from selected carcasses and raw ground products
      sampled prior to implementation of the Pathogen Reduction; Hazard Analysis and
      Critical Control Point Final Rule in the US.
AB  - In July 1996, the US Department of Agriculture (USDA), Food Safety and Inspection
      Service (FSIS), published the Pathogen Reduction; Hazard Analysis and Critical
      Control Point (HACCP) Systems final rule to improve food safety of meat and
      poultry products. The final rule established, among other requirements, pathogen
      reduction performance standards for Salmonella for food animal carcasses and raw
      ground products. The final rule is to be fully implemented in three stages in
      successively smaller federally inspected meat and poultry slaughter and
      processing establishments. Implementation began in January 1998 and was completed
      in January 2000. Samples of carcasses of four species of food animals (cattle,
      swine, chickens, turkeys), and raw ground product from each of these species,
      were collected by FSIS from establishments prior to implementation of the final
      rule and cultured for Salmonella. This paper reports Salmonella serotype results
      of samples collected from June 1997 through August 1998. These results represent
      a baseline for future comparisons.

PMID- 10898468
TI  - Listeria spp. in broiler flocks: recovery rates and species distribution
      investigated by conventional culture and the EiaFoss method.
AB  - The occurrence of Listeria monocytogenes in samples from broiler houses and
      cloacal swabs taken at the abattoir was investigated. An automated immunobased
      method (EiaFoss) was used, and 42 samples were also analysed by conventional
      culture; both methods were based on a two-step selective enrichment using
      CHR.4.17; Fraser and Fraser broths. L. monocytogenes was isolated from two of 71
      broiler flocks, yielding an estimated flock prevalence of 3%. The flock
      prevalence of L. inocua was estimated to 13%, and it was speculated that the
      potential of this apathogenic bacteria to grow faster than L. monocytogenes in
      enrichment broths may lead to an underestimation of the prevalence of L.
      monocytogenes. Furthermore, as L. inocua was also detected by the EiaFoss method,
      a significant amount of bacterial confirmation work had to be done. Of 42 samples
      analysed by conventional culture, four yielded L. inocua, of which two were not
      positive by EiaFoss.

PMID- 10898469
TI  - Mitochondrial DNA restriction enzyme analysis and evaluation of the enological
      characteristics of Saccharomyces cerevisiae strains isolated from grapes of the
      wine-producing area of Collio (Italy).
AB  - A total of 70 strains of Saccharomyces cerevisiae were isolated from different
      grapes from the Collio Region. Chemical parameters and mitochondrial DNA (mtDNA)
      restriction patterns were determined. Higher alcohols were the main parameter
      useful for differentiating between strains, whereas the mtDNA analysis
      demonstrated a high genetic variability between strains. A weak correlation was
      observed when the dendrograms obtained from the chemical and genetic results were
      compared.

PMID- 10898470
TI  - Assessment of the microbiological quality and wash treatments of lettuce served
      in University restaurants.
AB  - One hundred and forty-four samples of lettuce from 16 University restaurants were
      analyzed. The mesophilic aerobic counts of all samples ranged from 3.01 to 7.81
      log10 CFU g(-1). Results of total coliforms ranged from < 0.47 to > 3.38 log10
      most probable number (MPN) g(-1). Of the lettuce samples, 25.7% harbored
      Escherichia coli, 22.9% Staphylococcus aureus and 84% group D streptococci.
      Similarly, 10.4% of the samples harbored Aeromonas hydrophila, 2.8% Pseudomonas
      aeruginosa, and coliforms such as 14.6% Citrobacter freundii, 8.3% Klebsiella
      pneumoniae, 4.2% Enterobacter cloacae and 1.4% Providencia spp. Salmonella,
      Shigella and E. coli O157:H7 were not detected. When sodium hypochlorite or
      potassium permanganate solutions were used in washing procedures, the aerobic
      microorganisms were reduced by more than two log units, and total coliforms by at
      least one log.

PMID- 10898471
TI  - Report from the "World Conference on Science" (WCS), "Science for the Twenty
      First Century. A New Commitment", Budapest, Hungary, 26 June-1 July 1999.

PMID- 10898472
TI  - Automatic detection of open and closed eye states in the electroencephalographic
      (EEG) record for background EEG interpretation by the trigger method.
AB  - Automatic detection of open and closed eye states in electroencephalographic
      (EEG) records was investigated in this study as a part of procedures for the
      precise interpretation of the background EEG to achieve a comprehensive automatic
      EEG interpretation system. The features of eye open and closure were extracted
      from the EEG using a Markov process amplitude (MPA) EEG model, which could
      efficiently express the features of the EEG using a small number of parameters. A
      new technique, named the trigger method, was also developed to overcome the
      difficulty resulting from large differences in the EEG features among different
      subjects, because an accurate detection could not be obtained by using the
      conventional threshold method. The proposed method gave satisfactory results
      which conformed with those of visual inspection by a qualified EEGer and could be
      clinically used as a preprocessing method for the automatic interpretation of the
      awake background EEG.

PMID- 10898473
TI  - Functions of masseter and temporalis muscles in the control of temporomandibular
      joint loading--a static analysis using a two-dimensional rigid-body spring model.
AB  - Masticatory forces or bite forces applied to the teeth are known to generate a
      compressive force on the temporomandibular joint (TMJ). This intra-articular
      force is referred to as TMJ loading. TMJ loading is considered to be controlled
      to a certain extent by the stomatognathic system, so as not to exceed a certain
      limit. In order to clarify the control mechanism of the TMJ during biting, the
      controllability of TMJ loading through coordinated activities of the masticatory
      muscles has been numerically analyzed using a static two-dimensional jaw model.
      This model consists of a rigid-body model of the jaws and a spring model of the
      articular disk, which includes three dominant muscle force vectors representing
      the masseter, temporalis and lateral pterygoid muscles. The bite force vector is
      assumed to be applied solely at the first molar. Static equilibrium analyses
      suggest that coordinated activities of the masseter muscle and anterior portion
      of the temporalis muscle can minimize TMJ loading and concentrate the stress
      within the articular disk to the intermediate zone of the disk, and that the
      activity of the posterior portion of the temporalis muscle has the possibility of
      reducing TMJ loading.

PMID- 10898474
TI  - Modulation of neural activities during visual processing in the human
      extrastriate visual cortex.
AB  - Magnetoencephalographic responses to single letters (Japanese monosyllabic
      characters) presented in the left visual field were measured during visual
      cognition tasks, in which subjects judged matching of characters in two different
      processes based on phonological and graphical cues. Equivalent current dipoles,
      which represent focal neural activities, were localized in the extrastriate
      visual cortex of the occipital to occipitotemporal regions. The main activities
      were observed in the right lateral area when the subjects detected shape, and
      also in the medial and inferior areas of both hemispheres when they detected
      rhyme. These results suggest that the neural activities in the extrastriate
      cortex, which are related to early processing of familiar visual forms, can be
      modified by the top-down control.

PMID- 10898475
TI  - Influence of a fat on muscle oxygenation measurement using near-IR spectroscopy:
      quantitative analysis based on two-layered phantom experiments and Monte Carlo
      simulation.
AB  - The influence of a subcutaneous fat layer on measurement of muscle oxygenation
      using near-IR spectroscopy was quantitatively investigated by two-layered phantom
      experiments and Monte Carlo simulations, with the aim of developing an algorithm
      that can correct this influence. The phantom consisted of a fat-like layer, which
      was a mixture of agar and titanium dioxide powder, and a muscle-like layer, which
      was suspension of washed bovine blood in Intralipid solution. An LED with 760 and
      840 nm elements was used as an optical source, and the backscattered light was
      detected by photodiodes at source-detector distances of 20, 30 and 40 mm. The
      relationships between changes in optical density and blood concentrations were
      obtained at fat-like layer thicknesses of 0.5,10 and 15 mm under fully oxygenated
      and fully deoxygenated states. It was experimentally found that the change in
      optical density is significantly decreased and the linearity of measurement
      characteristics is clearly distorted by the presence of a fat layer. In the
      simulations, normalized light reflectance and mean optical pathlength in a muscle
      layer were calculated. The simulation results of the light reflectance agreed
      well with the experimental results. When the absorption in a muscle layer was
      relatively high, the mean optical pathlength in the muscle layer, or the
      measurement sensitivity, was not so dependent on the absorption. Therefore, the
      modified Beer-Lambert law can still be applied to estimate changes in muscle
      absorption from changes in optical density, even when a fat layer is involved.
      The results of simulation also suggested that the influence of a fat layer can be
      eliminated by correcting the measurement sensitivity using the fat layer
      thickness.

PMID- 10898476
TI  - Maximal flow pulsation in the pial arterioles of rats at increased intracranial
      pressure.
AB  - Red cell velocity in the brain pial arterioles ( 12-58 microm in diameter) of
      rats was measured by a fiber-optic laser-Doppler anemometer microscope to study
      the effects of intracranial pressure (ICP) on flow pulsation. The amplitude of
      velocity pulsation in the pial arterioles was 24+/-9% (mean +/- SD) of the
      temporal mean velocity under normal physiological conditions (ICP = 5 mmHg). It
      increased gradually up to 40+/-11% with increasing ICP up to 50 mmHg on average.
      It also increased with the vessel diameter at fixed values of ICP. In each
      arteriole, the velocity amplitude increased steeply at a critical value of ICP as
      ICP increased. The critical value of ICP ranged between 20 and 40 mmHg,.
      increased with the vessel diameter, and decreased downstream along arterial
      trees. These results suggest a correlation between the critical ICP and the
      internal pressure of the pial arteriole.

PMID- 10898477
TI  - Acquisition and analysis of brainstem auditory evoked responses of normal and
      diseased subjects by spectral estimation.
AB  - Human brainstem auditory evoked responses (BAERs) are sensory evoked potentials
      that can be recorded within a few milliseconds following a transient acoustic
      stimulus (click signal). This paper suggests a novel technique to clearly
      demarcate normals and patients with complaints of vertigo and deafness by
      computing hitherto unused power spectral parameters from the BAER signals
      recorded on them. The BAER spectrum of normal subjects contains three main
      frequency components, i.e. low-, mid- and high-frequency components around 100,
      500 and 1000 Hz, respectively, which is not so in the case of diseased subjects.
      The spectral parameters, i.e. the mean power frequency, median frequency, the
      ratios of the integrated power at dominant frequencies to that of the total power
      in spectrum and change in spectral power (CP) between these dominant frequency
      components are used to classify the recorded BAER signals into those of normals
      and the patients, and aid the clinician in quick and better diagnosis. The ranges
      of CP are estimated for the different groups and appear to be the most dominant
      parameter in the classification of the BAER signals.

PMID- 10898478
TI  - Gibberellic acid (GA3) induced changes in proanthocyanidins and malt quality of
      two- and six-row husked barleys.
AB  - Analysis of husked barleys for proanthocyanidins and malt quality attributes has
      shown that not a single variety is free of proanthocyanidins. The
      proanthocyanidins in barley grains varied from 3.85 to 4.94 mg/g as catechin
      equivalent. The concentration of proanthocyanidins decreased, while total soluble
      sugars, reducing sugars, diastatic power and beta-amylase activity increased
      during maltings as well as with exogenous gibberellic acid (GA3) application.
      Alfa 93 (two-row) and RD2560 (six-row) varieties appeared to be superior for
      malting and brewing purposes on the basis of proanthocyanidins, total phenols,
      diastatic power and beta-amylase activity. It is suggested that exogenous
      application of GA3 at 15 ppm may be useful for producing good quality malt from
      barley grains.

PMID- 10898479
TI  - Effect of soaking, cooking and germination on the oligosaccharide content of
      selected Nigerian legume seeds.
AB  - The identity and quantity of and effect of processing on raffinose
      oligosaccharides in raw, mature seeds of lima beans (Phaseolus lunatus), pigeon
      peas (Cajanus cajan), African yam beans (Sphenostylis sternocarpa) and jackbeans
      (Canavalia ensiformis) were investigated. Sucrose, raffinose, stachyose and
      verbascose were identified by HPLC in all the legume seeds. The total alpha
      galactoside contents of the seeds in decreasing order were African yam beans 3.84
      mg/100 mg; white lima beans 3.62 mg/100 mg; cream pigeon peas 3.51 mg/100 mg; red
      lima beans 3.37 mg/100 mg; jackbeans 2.83 mg/100 mg and brown pigeon peas 2.34
      mg/100 mg. The predominant oligosaccharide was verbascose in pigeon peas and
      stachyose in the other three legumes. Cooking unsoaked seeds brought about a
      greater reduction in the total alpha-galactoside content than soaking for nine
      hours. The removal of oligosaccharides was higher in legumes cooked in alkaline
      solution than in water. Germination quantitatively reduced raffinose, stachyose
      and verbascose while sucrose was increased in all seeds except red lima beans and
      jackbeans.

PMID- 10898480
TI  - Aerobic spore-forming bacteria and chemical composition of some Nigerian
      fermented soup condiments.
AB  - A total of 97 strains of spore-forming Bacillus were isolated from 45 samples of
      three Nigerian fermented condiments, obtained from retail markets located in
      Southwestern Nigeria. The isolates were identified as B. subtilis (33%), B.
      pumilus (19%), B. licheniformis (22%), B. brevis (9%), B. megaterium (12%) and B.
      polymyxa (5%). The microbial load of the condiments showed that the average count
      of spore-formers was between 107 to 109 cfu/g. The moisture contents of iru, ugba
      and ogiri were 57.18%, 46.32% and 42.34%, respectively, while the protein
      contents were 18.26%, 17.17% and 17.96%. The percentage fat was 29.88%, 40.25%
      and 44.14% for iru, ugba and ogiri. The ash content ranged from 5.8 to 6.1%; a
      0.1% titratable acidity and pH values above 7.0 were obtained for the three
      condiments.

PMID- 10898481
TI  - Quality attributes and storage stability of locally and mechanically extracted
      crude palm oils in selected communities in Rivers and Bayelsa states, Nigeria.
AB  - The effect of different extraction methods on the quality of crude palm oil
      processed using traditional (local) and mechanical methods in selected areas of
      Rivers and Bayelsa States and their storage stability were investigated. Certain
      quality determining parameters such as free fatty acids (FFA), peroxide value
      (PV), saponification value (SV), moisture, impurities and volatile matter (MIV)
      content were determined prior to and after storage for three months. The free
      fatty acids (FFA) ranged from 7 to 19 percent, peroxide value (PV) ranged from 3
      mEq/kg to 6 mEq/kg and moisture, impurity and volatile matter (MIV) ranged from
      0.21 to 0.64 percent for locally extracted crude palm oil samples and
      mechanically extracted crude palm oil samples. There was no significant
      difference (p > 0.05) in the FFA of samples A and E before and after storage for
      3 months. Also two of the locally extracted crude samples (A and E) stored better
      while one of the samples (D) showed a high level of deterioration as shown in its
      high levels of FFA, PV and IV values. Samples A and E resulted in a better
      quality of oil in terms of FFA (av. 7.25%) and PV (av. 4.5 meg/kg) when compared
      to the mechanically extracted one (sample C) with FFA (10.0%) and PV (5.78
      mEq/kg). However, all the locally and mechanically extracted crude palm oil
      samples could not meet the industrial and international standard quality for
      crude palm with FFA (2-5%) and PV (2-3.5 mEq/kg). Among the three different
      storage containers used under different storage conditions, plastic containers
      (PC) resulted in a better storage stability of the crude palm oils in terms of
      FFA, SV, and IV than transparent bottles stored on shelves (TBS) and amber
      colored bottles stored on the bare floor (BPF).

PMID- 10898483
TI  - Physicochemical, microbiological and sensory changes in stored plantain chips.
AB  - Plantain chips were produced from unripe plantain fruits. The chips were packed
      in polyethylene bags and stored at 30 +/- 2 degrees C for 1, 2 and 3 months,
      respectively. The storage stability of the chips was evaluated by analyzing
      periodically for changes in the physicochemical, microbiological and sensory
      characteristics. Protein and ash contents of the chips did not change (p > 0.05)
      over time. Fat decreased slightly (p > 0.05) over time. Vitamin C decreased and
      was negatively correlated with storage time (r = -95; p < 0.05). Peroxide value
      and microbial count increased with storage (p < 0.05). Sensory scores for chips
      did not change (p > 0.05) at 2 months storage, but, thereafter, decreased (p <
      0.05).

PMID- 10898482
TI  - An evaluation of the effect of Bacillus cells and Bacillus spores in association
      with cowpea granules as starter cultures for the fermentation of African oil bean
      (Pentaclethra macrophylla Bentham) to 'ugba'.
AB  - Studies on the improvement of the traditional production of 'ugba', a protein
      rich fermented African oil bean seed product, were undertaken, by developing
      starter cultures of Bacillus subtilis cells and spores in association with cowpea
      granules. The viability of the cells in association remained stable at 94.5% for
      6 months at 30 degrees C and for up to 10 months at 4 degrees C while the
      viability of the spores in association remained stable at ca. 96% for up to 10
      months at both 4 and 30 degrees C. The starter cultures resulted in high
      increases in protease activity from ca 2.8 mg N/min to about 51.6 +/- 0.4 mg
      N/min in 48 h and a corresponding increase in amino-nitrogen content of ca 2.0 +/
      0.2 mg N 100 g dry matter (DM) to ca 18.5 +/- 0.3 mg N/100 g (DM) during the
      same period. Changes in the protease activity of the natural process were gradual
      and increased from 3.0 mg N/min to 38.0 +/- 0.8 mg N/min after 5 days of
      fermentation. The maximum amino nitrogen content of 'ugba' produced by the
      starter cultures (18.5 +/- 0.3 mg N/100 g DM) after 2 days was significantly (p
      <0.05) higher than the maximum amino nitrogen content (12.5 +/- 0.8 mg N/100 g
      DM), of 'ugba' obtained by the natural process. 'Ugba' produced by the starter
      cultures were well accepted and compared favorably with the natural product.

PMID- 10898484
TI  - Effect of feeding crude red palm oil (Elaeis guineensis) and grain amaranth
      (Amaranthus paniculatus) to hens on total lipids, cholesterol, PUFA levels and
      acceptability of eggs.
AB  - Eggs, though a very nutritious food, also have high amounts of cholesterol and
      hence are not recommended to be consumed regularly by persons having
      hypercholesterolemia and associated cardiovascular diseases (CVD). In this
      context, an attempt was made in this study to reduce the cholesterol content of
      eggs by diet manipulation, using two naturally available and already proved
      hypocholesteromic agents [red palm oil (RPO) and grain amaranth]. Thirteen
      experimental rations using raw and popped grain Amaranth and RPO were fed to 24
      weeks old hens for a period of 6 weeks, singularly and in combinations. Total
      lipids, cholesterol and PUFA contents were analyzed in the experimental and
      control eggs. The results showed that RPO and RPO + popped amaranth feeding
      resulted in a maximum reduction in total lipids and cholesterol contents.
      Significant increase was observed in linoleic acid content in RPO + popped
      amaranth; raw amaranth and RPO fed groups. Acceptability studies showed that the
      products made from lower cholesterol eggs were well accepted.

PMID- 10898485
TI  - Color of single-screw extruded blends of soy-sweet potato flour --a response
      surface analysis.
AB  - Blends of defatted soy flour and sweet potato flour were extruded in a single
      screw extruder run at varying pre-set rotational speeds. Die diameter of the
      extruder was also varied. A central composite, rotatable nearly orthogonal
      response surface design was used in studying the interactive effects of extrusion
      variables on color of the extrudates. Color of raw and processed samples was
      determined on a DRLANGE Tricolor LFM3 instrument. Measurements were made in
      duplicates to obtain the CIELAB L*a*b* values. Results showed that whiteness (L*)
      decreased with increase in sweet potato in the blends during extrusion. Reduction
      in whiteness (darkening) evidenced in decreased L* values of samples was only
      affected by increase in sweet potatoes in the blends. Redness (a*) significantly
      increased as sweet potatoes content increased, which confirmed the decrease in
      whiteness. Yellowness (b*) also increased considerably, but as a result of the
      die diameter.

PMID- 10898486
TI  - Effects of extrusion cooking on some functional properties of soy-sweet potato
      mixtures--a response surface analysis.
AB  - Mixtures of defatted soy flour and sweet potatoes were extruded at 0:100, 25:75,
      50:50, 75:25 and 100:0 ratios in an Insta-Pro 600 single screw extruder operated
      at 180, 200, 220 rpm. Oil (3-5%) was added into the mix before extrusion. A 5 x
      32 fractional factorial central composite response surface design was adopted for
      investigating the variables: feed composition, % oil, and screw rotation speed
      (RPM). Percent oil and screw speed were randomly investigated at three levels,
      while feed composition was randomly investigated at five levels. Effect of
      extrusion cooking on functional properties: bulk density, expansion ratio, water
      absorption and solubility indices and trypsin inhibitor were assessed. Results
      showed that feed composition and screw speed had strong influences on the
      process. The effect of adding oil, into defatted soybean significantly (p < 0.05)
      affected only trypsin inhibitor content. High extrusion temperature (> 130
      degrees C), and accompanying high shear, were the result of the non-pasting
      nature of the extrudate. Therefore the products may have limited uses.

PMID- 10898487
TI  - Sequence analysis or rat integrin alphaE1 and alphaE2 subunits: tissue expression
      reveals phenotypic similarities between intraepithelial lymphocytes and dendritic
      cells in lymph.
AB  - The integrin alphaOX-62 subunit is defined by the OX-62 monoclonal antibody that
      was raised against rat dendritic cells in lymph (veiled cells) and shows
      properties similar to those of human alphaE that is predominantly expressed on
      intraepithelial lymphocytes. To clone alphaOX-62, rat probes generated using
      primers specific for the human alphaE sequence were used to screen rat T cell
      cDNA libraries. cDNA clones encoding two similar but not identical alpha subunits
      that are closely related but distinct from human alphaE were isolated. alphaE1 is
      predicted to be the rat homolog of mouse alphaM290 and alphaE2 corresponds to rat
      alphaOX-62. Immunofluorescence analysis revealed that mouse alphaE1 and rat
      alphaE2 are expressed in dendritic epidermal T cells in the skin, intraepithelial
      lymphocytes in the small intestine and in cells with a dendritic morphology
      present at sites where gammadelta T cells occur in lymphoid organs. Unexpectedly,
      in veiled cells alphaE2 is co-expressed with intracellular CD3-delta and a 33-kDa
      CD3 chain but not the T cell receptor. These findings suggest that veiled cells
      may be derived from a lymphoid precursor. Furthermore, veiled cells show
      phenotypic similarities to intraepithelial lymphocytes.

PMID- 10898488
TI  - CD4+CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen
      presenting cells.
AB  - CD4+CD25+ T cells have been shown to inhibit experimentally induced organ
      specific autoimmune disease and depletion of these regulatory T cells from normal
      mice results in development of such conditions. Furthermore, CD4+CD25+ T cells
      suppress the IL-2 production and thereby the proliferation of polyclonally
      activated CD4+CD25- T cells in vitro. The suppression in vitro is independent of
      secreted factors but requires interactions between CD4+CD25- and CD4+CD25+ T
      cells and antigen-presenting cells (APC). We have now further investigated the
      function of CD4+CD25+ T cells in vitro and have focused on their interactions
      with APC. We found that CD4+CD25+ T cells down-regulated the expression of the co
      stimulatory molecules CD80 and CD86 on dendritic cells. The steady-state level of
      CD80 mRNA was also decreased, while the steady-state level of CD86 mRNA was not,
      suggesting that distinct mechanisms regulate the expression of these molecules.
      The down-regulation occurred even in the presence of stimuli that would normally
      increase the expression of CD80 and CD86 molecules. Thus, down-regulation of co
      stimulatory molecules may be an additional effector function of these regulatory
      T cells.

PMID- 10898489
TI  - Neonatal invariant Valpha24+ NKT lymphocytes are activated memory cells.
AB  - NKT cells are a small subset of T lymphocytes which express an invariant
      V(alpha24JalphaQ TCR and recognize glycolipids presented by CD1d. In adults, NKT
      cells have a memory phenotype, frequently associated with oligoclonal expansion,
      express NK cell markers, and produce TO cytokines upon primary stimulation.
      Because of these features, NKT cells are regarded as lymphocytes of innate
      immunity. We investigated NKT cells from cord blood to see how these cells appear
      in the absence of exogenous stimuli. We found that NKT cells are present at
      comparable frequencies in cord blood and adult peripheral blood mononuclear cells
      and in both cases display a memory (CD45RO+CD62L-) phenotype. However, neonatal
      NKT cells differ from their adult counterparts by the following characteristics:
      (1) they express markers of activation, such as CD25; (2) they are polyclonal;
      (3) they do not produce cytokines in response to primary stimulation. Together,
      our data show that human NKT cells arise in the newborn with an activated memory
      phenotype, probably due to recognition of an endogenous ligand(s). The absence of
      oligoclonal expansion and primary effector functions also suggest that neonatal
      NKT cells, despite their activated memory phenotype, require a further
      priming/differentiation event to behave as fully functional cells of innate
      immunity.

PMID- 10898490
TI  - Prolonged exposure of mouse macrophages to IFN-beta suppresses transcription of
      the inducible nitric oxide synthase gene: altered availability of transcription
      factor Stat1alpha.
AB  - Previous studies from our laboratory have shown that prolonged exposure of mouse
      macrophages to IFN-beta interferes with their subsequent ability to become
      activated for tumor cell killing. Data reported here show that such inhibition is
      due to reduced production of NO, resulting from decreased transcription of the
      gene that encodes inducible NO synthase (iNOS; EC 1.14.13.39). The molecular
      basis for such suppression was shown to be, at least in part, decreased nuclear
      accumulation of tyrosine-phosphorylated Stat1alpha (pStat1alpha), and a
      consequent change in the nuclear ratio of pStat1alpha to non-transactivating
      pStat1beta. Reduced phosphorylation was observed despite the fact that time
      course studies revealed greater than normal quantities of both Stat1alpha and
      Stat1beta proteins in macrophages that had been pre-exposed to IFN-beta. The
      decrease in nuclear pStat1alpha was demonstrated to involve an increase in the
      rate of turnover of phosphorylated protein. The homodimeric form of pStat1alpha
      is essential for the expression of both the iNOS and IFN-regulatory factor-1
      genes (the product of the latter is necessary for full expression of the iNOS
      gene). These results have broad implications, because they suggest that limiting
      the availability of homodimeric pStat1alpha is a means by which down-regulation
      of genes containing promoter-linked IFN-gamma-activated sites might be achieved.

PMID- 10898491
TI  - Differential desensitization of lipopolysaccharide-inducible chemokine gene
      expression in human monocytes and macrophages.
AB  - Bacterial lipopolysaccharide (LPS) has been shown to induce a wide variety of pro
      inflammatory cytokines and chemokines. An initial challenge with minute amounts
      of LPS causes tolerance to later LPS effects which is characterized by a much
      lower or abrogated release of pro-inflammatory cytokines. To explore the
      relationship between the production of chemokines and the induction of LPS
      tolerance, we pretreated human monocytes with increasing LPS doses and thereafter
      restimulated with LPS. The re-expression of the CC chemokines macrophage
      inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES was substantially
      suppressed after pre-incubation with low LPS doses. In striking contrast, the re
      expression of neutrophil-attracting IL-8 and melanoma growth stimulatory activity
      alpha and of the monocyte-attracting monocyte chemotactic protein-1 remained high
      and was, in part, initially increased after restimulation with LPS. The
      corresponding gene expression pattern as determined by Northern blot analyses
      correlated closely with the release of chemokines and cytokines. Thus, a basic
      set of chemotactic mediators that are still produced by otherwise LPS
      desensitized monocytes/macrophages may ensure the continuing recruitment of
      monocytes and neutrophils into an inflammatory process caused by gram-negative
      bacteria.

PMID- 10898492
TI  - Collagen-induced arthritis in C57BL/6 (H-2b) mice: new insights into an important
      disease model of rheumatoid arthritis.
AB  - Collagen-induced arthritis (CIA) is a widely used model of rheumatoid arthritis
      (RA) and has been important for understanding autoimmunity. CIA is purportedly
      restricted to mice bearing the MHC class II H-2q or H-2r haplotypes. In this
      study, we re-examined established concepts regarding susceptibility to CIA. We
      found mice derived from the C57BU6 (B6) (H-2b) background can develop CIA with
      high incidence (60-70%), and sustained severity by using an immunization
      procedure modified for optimum response in DBA/1 (D1) (H-2q) mice. Clinically and
      histologically the B6 disease resembles that of D1 mice and is dependent on
      immunization with type II collagen, as well as on B and CD4+ T cells. In
      contrast, 129/Sv mice, which share H-2b, are resistant to CIA. We conclude that
      susceptibility to CIA may reflect immunization conditions and/or important
      contributions from non-MHC genes, revealed by different immunization protocols. A
      practical outcome is that CIA can be directly applied to gene knockout mice
      generated from B6 embryonic stem cells without need for backcross onto the D1
      background. This model may lead to improved understanding of autoimmunity in CIA
      and RA and may provide a platform for analysis of the contribution of non-MHC
      genes to CIA.

PMID- 10898493
TI  - CD19 signal transduction in normal human B cells: linkage to downstream pathways
      requires phosphatidylinositol 3-kinase, protein kinase C and Ca2+.
AB  - CD19 is required for normal antibody responses in mice. We have shown that CD19
      enhances the activation of extracellular signal-regulated kinase (ERK) 2 by
      membrane (m) IgM but otherwise little is known of CD19 signaling in primary human
      cells. We now ask which pathways link CD19 with ERK2 in human tonsillar B cells.
      In analyses of signaling intermediates, the phosphatidylinositol 3-kinase (PI3K)
      inhibitor wortmannin partially suppressed the release of Ca2+ induced by
      coligation of CD19 and mIgM but the selective PKC inhibitor bisindolylmaleimide I
      (BIM-I) did not. The Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid, BIM-I and wortmannin each had only a small effect on ERK2
      activation induced by surface IgM alone but blocked the enhancement of that
      activation by CD1 9/mIgM coligation. To analyze the mitogen-activated protein
      kinase (MAPK) cascade, we measured activation of Raf, MAPK- or ERK kinase (MEK) 1
      and ERK2. CD19 consistently enhanced activation of ERK2 and MEK1. However,
      synergistic activation of Raf was variably observed. In subpopulation analyses,
      synergistic activation of Raf1 was consistently observed in the IgDlow but not in
      the IgDhigh cells. Thus, in normal human B cells, PI3K is upstream of the Ca2+
      response while PI3K, Ca2+ release and protein kinase C are all required for ERK2
      activation, and CD19 enhances the MAPK cascade at multiple levels, depending on
      the state of differentiation.

PMID- 10898494
TI  - Vav modulation of the Ras/MEK/ERK signaling pathway plays a role in NFAT
      activation and CD69 up-regulation.
AB  - Vav is expressed exclusively in hematopoietic cells and becomes phosphorylated on
      tyrosine in response to antigen receptor ligation. Although Vav can act as a Rac
      specific guanine nucleotide exchange factor in vitro and as a c-Jun N-terminal
      kinase (JNK) activator in ectopic expression systems, its physiological functions
      in lymphocytes remain unclear. Indirect evidence suggests that Vav interacts with
      the Ras/ERK pathway in T cells. Here, we analyzed the effects of Vav on three
      known downstream targets of Ras, i. e. activation of ERK and NFAT, and up
      regulation of the activation antigen CD69. The MEK inhibitor PD90859 inhibited
      Vav-induced activation of ERK, and Vav- or anti-CD3-induced activation of NFAT,
      suggesting that MEK and ERK are involved in Vav-mediated NFAT activation.
      Similarly to Ras, Vav cooperated with constitutively active calcineurin and with
      ERK to activate NFAT, and was capable of up-regulating CD69 expression in T
      cells. Moreover, these Vav-mediated functions were all inhibited by a dominant
      negative Ras mutant. Conversely, however, dominant negative Vav did not inhibit
      NFAT and ERK activation or CD69 expression induced by an active Ras mutant. These
      findings indicate that Ras functions as an important downstream target of Vav in
      signaling pathways that lead to NFAT and ERK activation, and to CD69 expression.
      Moreover, the finding that Vav- (or Ras-) induced CD69 expression was not
      inhibited by a dominant negative Rac mutant indicates that Vav mediates some Ras
      dependent, but Rac-independent, functions in T cells.

PMID- 10898495
TI  - Targeting and selection of mutations in human Vlambda rearrangements.
AB  - The impact of somatic hypermutation on the lambda light chain repertoire of
      individual IgM+ peripheral B cells in the absence (nonproductive rearrangements)
      and presence (productive rearrangements) of selective influences was analyzed. In
      the 27 mutated nonproductive VlambdaJlambda, rearrangements obtained from
      individual peripheral B cells, a significantly greater mutational frequency was
      observed in the complementarity-determining region (CDR) in comparison to the
      framework region (FR), whereas the mutational frequencies in both the CDR and FR
      of the 100 mutated productive VlambdaJlambda rearrangements were significantly
      greater. R mutations were introduced comparably in CDR and FR of nonproductive
      VlambdaJlambda rearrangements, but were significantly decreased in FR of
      productive VlambdaJlambda rearrangements. The majority of codons defined as hot
      spots for R mutations were within CDR in both the nonproductive and productive
      VlambdaJlambda rearrangements. Targeting of mutations to RGYW/WRCY motifs was
      observed such that 38% of all mutations in the nonproductive VlambdaJlambda
      rearrangements were within RGYW/WRCY motifs. Mutations in RGYW/WRCY motifs were
      positively selected and accounted for >50% of all mutations in the mutated
      productive VlambdaJlambda rearrangements. These data indicate that targeting of
      the mutational machinery and selection of mutations in these targeted motifs play
      major roles in influencing nucleotide changes in VlambdaJlambda rearrangements.

PMID- 10898496
TI  - Role of selectins in experimental Staphylococcus aureus-induced arthritis.
AB  - The selectin family of adhesion molecules mediates the initial attachment of
      leukocytes to venular endothelial cells at sites of tissue injury and
      inflammation. To assess the role of selectin family in Staphylococcus aureus
      triggered septic arthritis, we used several approaches. First, treatment with
      fucoidin, a carbohydrate molecule capable of binding to and blocking selectin
      functions, was used. In addition, we used P-selectin gene-targeted mice as well
      as mice pretreated with monoclonal antibody blocking L-selectin function. The P
      selectin-deficient and fucoidin-treated animals initially exhibited a less severe
      septic arthritis both clinically and histopathologically. In the later stages of
      the disease no significant differences with respect to arthritis were evident.
      Pretreatment with L-selectin blocking antibody did not influence the severity of
      arthritis. High numbers of staphylococci were recovered from the kidneys of
      selectin-deficient mice, indicating a less efficient clearance of bacteria. Our
      results demonstrate a dual role for selectins in S. aureus-induced arthritis: on
      the one hand, blockade of these selectins leads to less severe arthritic lesions
      in the initial stage of the disease; on the other, delayed recruitment of
      phagocytes decreases the clearance of bacteria.

PMID- 10898497
TI  - Common cytokine receptor gamma chain (gammac)-deficient B cells persist in T cell
      deficient gammac-mice and respond to a T-independent antigen.
AB  - Defects in the common cytokine receptor gamma chain (gammac) in man result in X
      linked severe combined immunodeficiency disease (SCIDX1) characterized by an
      absence of alphabeta T cells, gammadelta T cells and NK cells, with the presence
      of circulating B cells. Mice made deficient for gammac lack gammadelta T cells
      and NK cells, but in contrast to SCIDX1 patients have appreciable numbers of
      alphabeta T cells, while B cells are reduced about tenfold in numbers and
      disappear with age. Here we show that when gammac- mice are rendered T cell
      deficient, B cell numbers are still reduced but the age-dependent loss of B cells
      does not occur. The peripheral B cells which persisted in gammac-/ nude and
      gammac-/TCRbeta-/- mice were able to respond to mitogen stimulation in vitro and
      to mount antigen-specific T-independent Ig responses in vivo. These results
      demonstrate that gammac- B cells are functionally competent and suggest that
      residual alphabeta T cells are implicated in the B cell loss in gammac mice. The
      gammac-/nude and gammac-/TCRbeta-/- mice provide new models to dissect the role
      of gammac-dependent receptors during murine B cell differentiation.

PMID- 10898498
TI  - HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on
      decidual NK cells.
AB  - Non-classical MHC class I molecule HLA-E is the ligand for CD94/NKG2 NK cell
      receptors. Surface expression of HLA-E requires binding of specific HLA class I
      leader sequences. The uterine mucosa in early pregnancy (decidua) is infiltrated
      by large numbers of NK cells, which are closely associated with placental
      trophoblast cells. In this study we demonstrate that trophoblast cells express
      HLA-E on their cell surface in addition to the previously reported expression of
      HLA-G and HLA-C. Furthermore, we show that the vast majority of decidual NK cells
      bind to HLA-E tetrameric complexes and this binding is inhibited by mAb to CD94.
      Thus, recognition of fetal HLA-E by decidual NK cells may play a key role in
      regulation of placentation. The functional consequences of decidual NK cell
      interaction were investigated in cytotoxicity assays using polyclonal decidual NK
      cells. The overall effect of CD94/NKG2 interaction with HLA-E is inhibition of
      cytotoxicity by decidual NK cells. However, since decidual NK cells are unable to
      kill trophoblast even in the presence of mAb to MHC class I molecules and NK cell
      receptors, HLA-E interaction with CD94/NKG2 receptors may regulate other
      functions besides cytolysis during implantation.

PMID- 10898499
TI  - Co-stimulation of IL-2 production by CD28 is independent of tyrosine-based
      signaling motifs in a murine T cell hybridoma.
AB  - In addition to the antigen-specific stimulus delivered by the TCR, T cells under
      most circumstances require a co-stimulatory signal for complete activation. CD28
      can provide this signal, and the importance of CD28-mediated co-stimulation has
      been well documented both in vitro and in vivo, but the intracellular pathways
      downstream of CD28 are less well characterized. So far, maximal co-stimulation of
      IL-2 production has been attributed to tyrosine-based signaling motifs, either
      including the first cytoplasmic tyrosine residue that binds phosphatidylinositol
      3'-kinase (PI3-K), or the third tyrosine residue. Here we describe results of the
      expression of murine CD28 receptor mutants in a CD28-deficient murine T cell
      hybridoma, A1.1. We show that in A1.1 cells co-stimulation of IL-2 production is
      independent of CD28 cytoplasmic tyrosine residues, since a mutant lacking all
      four cytoplasmic tyrosines is still able to induce a full co-stimulatory
      response. Using truncation mutants, this activity can be attributed to amino
      acids 183 to 194, a sequence containing a conserved diproline motif that may
      recruit SH3 domains of other signaling molecules like Grb2. Thus we have
      identified a novel pathway for CD28-mediated co-stimulation of IL-2 production
      that is independent of PI3-K activity and phosphotyrosine-based signaling motifs.

PMID- 10898500
TI  - Allergen-derived long peptide immunotherapy down-regulates specific IgE response
      and protects from anaphylaxis.
AB  - To evaluate a long peptide-based allergy vaccine in a murine model, CBA/J mice
      were sensitized with low dose alum-adsorbed phospholipase A2 (PLA2), a major bee
      venom allergen. Presensitized mice were treated by daily i.p. injections of a
      mixture of three long overlapping peptides (44- to 60-mer) spanning the entire
      PLA2 molecule (100 microg/peptide) for 6 consecutive days. This therapeutic
      approach induced a sharp drop in PLA2-specific IgE, an increase in specific
      IgG2a, and a marked T cell hyporesponsiveness. T cell cytokine secretion was
      characterized by a shift from a Th2 to a Th1 profile. Prophylactic treatment of
      naive mice with long peptides prior to sensitization with PLA2 induced a
      comparable modulation of B and T cell responses. Upon i.p. challenge with native
      PLA2, presensitized mice treated with the long peptide mixture were fully
      protected from anaphylaxis. This indicated that allergen-derived long overlapping
      peptides were safe and able to modulate an established Th2 response or to prevent
      its development. Furthermore, long peptide-based immunotherapy provided clinical
      protection against anaphylaxis, thus appearing as a promising approach of the
      therapy of allergic diseases.

PMID- 10898501
TI  - Involvement of IFN-gamma receptor-medicated signaling in pathology and anti
      malarial immunity induced by Plasmodium berghei infection.
AB  - IFN-gamma has been implicated in the pathogenesis of experimental cerebral
      malaria (ECM). We have used mice lacking the alpha chain of the IFN-gamma
      receptor (KO mice) to define its role in the pathogenesis of ECM. Infected KO
      mice did not develop ECM and showed no leukocyte or parasite sequestration in the
      brain, and no hemorrhages. The resistance of KO mice to ECM was associated with
      the absence of any increases of TNF-alpha and ICAM-1 proteins in the brain, which
      are both essential for ECM. Wild-type (WT) mice which do not develop ECM, despite
      increased local production of TNF-alpha protein, showed no leukocyte accumulation
      in the brain and this was correlated with the absence of ICAM-1 protein from
      brain microvessels. KO mice infected with 106 parasitized erythrocytes (PE) of
      Plasmodium berghei ANKA (PbA) did not develop ECM, but they had high parasitemia
      and died earlier than WT mice which did not develop ECM. However, KO mice did not
      develop higher parasitemia than WT mice when both groups were infected with a
      lower dose (5x10(5) PE) of PbA-infected red blood cells. This indicates that
      different doses of PE may trigger different IFN-gamma responses and that there
      may be a threshold concentration for protection against parasitemia.

PMID- 10898502
TI  - Beta7 integrin-deficient mice: delayed leukocyte recruitment and attenuated
      protective immunity in the small intestine during enteric helminth infection.
AB  - The ontogeny and function of gut-associated-lymphoid tissue is known to be
      critically dependent on the beta7 integrin subfamily. We have investigated the
      development of intestinal inflammation and pathogen-specific protective immunity
      to enteric helminth infection in beta7 integrin knockout (KO) mice. During
      Trichinella spiralis infection of the small intestine there was a significant
      delay and reduction in the magnitude of intestinal eosinophilia and mastocytosis
      in the absence of P7 integrin, resulting in impaired host protection. Aberrant
      distribution of mast cells was also observed in the small intestine of infected
      KO mice. Adoptive transfer of primed wild-type mesenteric lymph node cells into
      T. spiralis-infected beta7 KO mice did not restore the intestinal mast cell
      response, suggesting that the defect in intestinal mastocytosis is due to the
      absence of beta7 expression on this population rather than an indirect
      consequence of reduced T cell numbers. In contrast, no impairment in leukocyte
      recruitment or protection against Trichuris muris infection of the large
      intestine was observed in KO mice. Taken together the data provide the first
      description of reduced leukocyte homing and attenuated protective immunity
      against helminth infection in beta7 KO mice. Furthermore, these results suggest
      that beta7 integrin-independent adhesion molecule interactions are deployed in
      the large but not small intestine during intestinal inflammation.

PMID- 10898503
TI  - A subpopulation of CD8+ T cells specific for melanocyte differentiation antigens
      expresses killer inhibitory receptors (KIR) in healthy donors: evidence for a
      role of KIR in the control of peripheral tolerance.
AB  - In cancer patients, NK cell inhibitory receptors (IR) are expressed on a fraction
      of melanoma-specific lymphocytes with a unique reactivity for tumor antigens
      derived from normal, nonmutated genes (differentiation antigens). It is presently
      not known whether expression of these receptors is induced during an immune
      response against melanoma cells or whether these receptors can be found on T
      cells harboring a self specificity for such differentiation antigens in healthy
      donors. By analyzing short-term cultures of CD8+ T cells primed in vitro with
      melanocyte differentiation antigens, we found expression of NK cell receptors on
      a small but consistent fraction of CD8+ T cells derived from healthy donors. Both
      long and short forms of NK cell receptors were expressed. Interestingly, only
      long forms were functional and inhibited effector functions (cytotoxicity and IFN
      gamma production) of these CD8+ T cells. Short forms were devoid of any
      detectable activating function. The presence of T cells specific for
      differentiation antigens and expressing NK cell receptors, with an exclusive
      inhibitory function, in healthy donors strengthens the notion that IR may serve
      to control T cell tolerance to some peripheral antigens.

PMID- 10898504
TI  - Analysis of CD8 T cell reactivity to cytomegalovirus using protein-spanning pools
      of overlapping pentadecapeptides.
AB  - The frequencies of human cytomegalovirus (HCMV) protein-specific CD8 T cells,
      identified by the presence of intracellular IFN-gamma, were measured by flow
      cytometry following stimulation of freshly isolated peripheral blood mononuclear
      cells (PBMC) with comprehensive peptide pools. These pools spanned the entire
      amino acid sequences of the HCMV pp65 and major immediate early (IE-1) proteins
      and consisted of 15-amino acid peptides with at least nine overlaps between
      neighboring peptides. As a result all potential CD8 T cell epitopes contained in
      these proteins were provided by the complete pools and, therefore, unlike with
      single epitopes, testing was independent of donor HLA type. Individual
      stimulating peptides from the same pools were identified in parallel experiments.
      Thus we found that our results with the complete pools using PBMC from 26 healthy
      HCMV-seropositive donors were 100% sensitive and specific with respect to
      predicting the presence of recognized epitopes in the respective proteins. In
      addition, cells from 15 renal transplant patients were tested with complete pools
      alone. While our results confirmed our previous contention that HCMV IE-1 is an
      important CD8 T cell target, the technical improvement we made in order to
      address this question has clearly wider implications. Similar pools may be
      applied to examine the role of proteins from other pathogens, in autoimmune
      disease or following vaccination.

PMID- 10898505
TI  - IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation
      pathway.
AB  - IL-10 induces T cell anergy in numerous mouse models and specific immunotherapy
      of allergy in humans. Here, we demonstrate that IL-10 directly acts on T cells
      which are stimulated via CD28 by efficiently blocking proliferation and cytokine
      production. T cells tolerized by IL-10 showed high viability and the unresponsive
      state was reversed by anti-CD3 monoclonal antibody (mAb) stimulation and IL-2,
      but not by anti-CD28 mAb stimulation. Signal transduction via CD28 requires CD28
      tyrosine phosphorylation and binding of phosphatidylinositol 3-kinase. IL-10
      inhibited tyrosine phosphorylation of CD28; thus, the phosphatidylinositol 3
      kinase binding to CD28 was blocked. Consequently, IL-10 inhibited the antigen
      induced secretion of both Th1 and Th2 cytokines, including IL-2, IFN-gamma, IL-4,
      IL-5 and IL-13. Furthermore, neutralization of endogenously produced IL-10
      significantly increased T cell proliferation and both Th1 and Th2 cytokine
      production in vitro. Using superantigen stimuli, T cell suppression by IL-10 was
      merely induced at low doses when co-stimulation by CD28 was essential. Together,
      these data demonstrate that IL-10 directly acts on the CD28 signaling pathway and
      this represents an important T cell suppression mechanism leading to anergy.

PMID- 10898506
TI  - Diagnosis of X-linked lymphoproliferative disease by analysis of SLAM-associated
      protein expression.
AB  - X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency in
      which affected boys show abnormal responses to Epstein-Barr virus infection. The
      gene defective in XLP has been identified and designated SH2D1A and encodes a
      protein termed SLAM-associated protein (SAP). Mutation analysis in individuals
      with typical XLP presentations and family histories has only detected
      abnormalities in approximately 60% of patients. Thus, genetic analysis alone
      cannot confirm a diagnosis of XLP We have developed a SAP expression assay that
      can be used as a diagnostic indicator of XLP We show that SAP is constitutively
      expressed in normal individuals, in patients with severe sepsis and in patients
      with other primary immunodeficiencies. In six XLP patients, four with classical
      and two with atypical presentations, SAP expression was absent. In the latter
      two, who were previously assigned as having common variable immunodeficiency
      (CVID), the diagnosis of XLP was initially made using the protein expression
      assay. In two further patients in whom no mutation could be detected by genetic
      analysis, lack of SAP expression strongly suggests that these individuals have
      XLP. We therefore suggest that XLP should be suspected in certain boys previously
      diagnosed as having CVID and recommend that patients are investigated both by
      genetic analysis of SH2D1A and by expression of SAP protein.

PMID- 10898507
TI  - Rat chromosome 9 bears a major susceptibility locus for IgE response.
AB  - Injection of Brown Norway (BN) rats with gold salts provides a model to analyze
      the genetic control of the IgE response. A cohort of F2 progeny of susceptible BN
      and resistant LEW strains has been studied to carry out a genome-wide search for
      loci controlling the IgE response. Genome scanning identified two previously
      described loci, Atps1 and Atps2, and a new locus, Atps3. Atps1 linked to the MHC
      and Atps2 linked to the cytokine gene cluster that included the IL-4 region have
      been previously associated with serum IgE concentrations and with other Th2
      dependent immune manifestations triggered by gold salts. The new interval, Atps3,
      identified on chromosome 9 (Lod score = 16), appears to play a major role in the
      control of the IgE response since it accounts for 31% of the genetic variance.
      Moreover, Atps3 is linked to anti-laminin antibody response and to glomerular
      immunoglobulin deposits. The identification and functional characterization of
      genes involved in these regions, particularly in Atps3, may shed light on the
      pathogenesis of atopic diseases in man.

PMID- 10898508
TI  - Mannan-binding lectin and C1q bind to distinct structures and exert differential
      effects on macrophages.
AB  - While the interaction of complement component C1q with cellular proteins is
      extensively studied, much less is known about the binding of the structurally
      related molecule, mannan-binding lectin (MBL) to various cells. Here we show by
      cytofluorimetry that the interaction of MBL with immunocompetent cells is much
      more restricted than that of C1q. It is shown that under conditions of
      physiological ionic strength MBL binds to human monocyte-derived macrophages
      (Mphi) and monocytoid cell lines, but not to T and B lymphocytes, in contrast to
      C1q, which interacts with all these cells under the same conditions. As opposed
      to the binding of C1q, low ionic strength does not improve the interaction of MBL
      with Mphi. No competition for cellular binding sites was found when MBL and C1q
      were added simultaneously to the cells. Studying the functional consequences of
      the interaction, we found that the release of TNF-alpha from Mphi is induced by
      C1q but not by MBL. Production of complement C3 by Mphi is stimulated by C1q
      strongly, while the effect of MBL is much weaker. C3 produced upon C1q-mediated
      triggering is shown to opsonize RBC, resulting in enhanced phagocytosis. These
      results suggest that cell membrane molecules binding MBL and C1 q are not
      identical; moreover, biological functions exerted by these proteins are also
      markedly different.

PMID- 10898509
TI  - Aldehyde-mannan antigen complexes target the MHC class I antigen-presentation
      pathway.
AB  - Antigens such as MUC1 coupled to oxidized mannan lead to rapid and efficient MHC
      class I presentation to CD8+ cells and a preferential T1 response; after
      reduction there is class II presentation and a T2 immune response. We now show
      that the selective advantage of the oxidized mannan-MUC1 is due to the presence
      of aldehydes and not Schiff bases, and that oxidized mannan-MUC1 binds to the
      mannose and not scavenger receptors and is internalized and presented by MHC
      class I molecules 1,000 times more efficiently than when reduced. After
      internalization there is rapid access to the class I pathway via endosomes but
      not lysosomes, proteasomal processing and transport to the endoplasmic reticulum,
      Golgi apparatus and cell surface. Aldehydes cause rapid entry into the class I
      pathway, and can therefore direct the subsequent immune response.

PMID- 10898510
TI  - Efficient protection against Mycobacterium tuberculosis by vaccination with a
      single subdominant epitope from the ESAT-6 antigen.
AB  - We have investigated the vaccine potential of two peptides derived from the 6-kDa
      early secretory antigenic target (ESAT)-6 antigen in the mouse model of
      tuberculosis. The peptides were both strongly immunogenic in B6CBAF1 (H-2b,k)
      mice and primed recall responses of the same intensity after immunization.
      However, both tuberculosis infection and immunization with ESAT-6 resulted in
      responses focused towards ESAT-61-20. Multiple antigen peptide constructs as well
      as free peptides were emulsified with dimethyl dioctadecylammonium
      bromide/monophosphoryl lipid A/IL-2 and tested as experimental vaccines in an
      i.v. and aerosol model of tuberculosis in mice. The peptide were highly
      immunogenic and induced cellular responses of the same magnitude. However, only
      vaccines based on the subdominant ESAT-651-70 epitope promoted significant levels
      of protective immunity and the level of protection was equivalent to that
      achieved with ESAT-6 and BCG. These findings demonstrate the potential of peptide
      based vaccines against tuberculosis and indicate that there is not direct
      correlation between the hierarchy of response to naturally processed peptides and
      their ability to induce protective immunity against Mycobacterium tuberculosis.

PMID- 10898511
TI  - A role for IL-5 in the induction of cytotoxic T lymphocytes in vivo.
AB  - IL-5 is generally regarded as a Th2 cytokine involved in eosinophil maturation
      and function and in B cell growth and antibody production, but without any well
      established effects on T cells. Early reports suggested that IL-5 could stimulate
      the production of cytotoxic T lymphocytes (CTL) in vitro, but no evidence has
      been obtained to date for such a role in studies with IL-5-deficient (IL-5-/-)
      mice. Here we demonstrate that when oxidized mannan MUC1 fusion protein (M-FP) is
      used as an antigen in mice, IL-5 is required for the optimal generation of the
      CTL response. IL-5 was as effective as IL-2 for the induction of CTL from spleen
      cells in vitro and both CD4+ and CD8+ T cells from M-FP-immunized animals could
      be shown to secrete IL-5 in culture. In IL-5-/- mice, CTLp frequency was greatly
      diminished resulting in the inability to reject MUC1- tumors. Clearly, IL-5 is
      produced by functional T cells, especially the Tc1 type, after M-FP immunization
      and is required for an optimal CTL response to this antigen.

PMID- 10898512
TI  - Fusogenic liposomes efficiently deliver exogenous antigen through the cytoplasm
      into the MHC class I processing pathway.
AB  - Exogenous soluble proteins enter the endosomal pathway by endocytosis and are
      presented in association with MHC class II rather than class I. In contrast, the
      delivery of exogenous protein antigens (Ag) into the cytosol generates MHC class
      I-restricted cytotoxic T lymphocytes (CTL) responses. Although several
      immunization approaches, such as the utilization of liposomes, have induced the
      in vivo priming of MHC class I-restricted CTL responses to protein Ag, it remains
      unclear whether this priming results from the direct delivery of protein Ag to
      the cytosol. Here we report that fusogenic liposomes (FL), which are prepared by
      fusing simple liposomes with Sendai virus particles, can deliver the encapsulated
      soluble protein directly into the cytosol of cells cultured concurrently and
      introduce it into the conventional MHC class I Ag presentation pathway. Moreover,
      a single immunization with ovalbumin (OVA) encapsulated in FL but not in simple
      liposomes results in the potent priming of OVA-specific CTL. Thus, FL function as
      an efficient tool for the delivery of CTL vaccines.

PMID- 10898513
TI  - Binding of Mycoplasma arthritidis-derived mitogen to human MHC class II molecules
      via its N terminus is modulated by invariant chain expression and its C terminus
      is required for T cell activation.
AB  - Mycoplasma arthritidis-derived mitogen (MAM) is considered to be a member of the
      super-antigen family despite the fact that there is no evidence until now
      indicating its binding to MHC class II molecules. To demonstrate its direct
      binding and to determine the regions involved in MHC class II and TCR
      interactions, we generated a recombinant wild-type and two truncated forms of the
      MAM protein. Data obtained in the course of the present investigation show that
      MAM binds specifically and significantly to human MHC class II molecules.
      Evidence is also provided that MAM bears two distinct binding regions: one is
      located within its N terminus and interacts with MHC class II molecules, while
      the second region which is located in its C terminus mediates its recognition by
      the TCR. Association of the MHC class II-associated invariant chain peptide with
      the peptide binding groove on the cell surface completely abolished MAM binding
      and presentation. This inhibitory effect is restored by the expression of HLA-DM
      molecules, suggesting that the nature of the peptide within the binding groove
      and/or the stability of the MHC class II molecules on the cell surface may
      modulate MAM/MHC class II interactions.

PMID- 10898514
TI  - cAMP-mediated growth inhibition of lymphoid cells in G1: rapid down-regulation of
      cyclin D3 at the level of translation.
AB  - cAMP is an important physiological mediator of lymphoid growth inhibition. The
      purpose of the present study was to establish the link between cAMP and the cell
      cycle machinery leading to inhibition of G1/S transition in human peripheral
      blood lymphocytes (PBL). To unravel immediate effects of cAMP on this part of the
      cell cycle machinery, lymphocytes were synchronized in mid to late G1 after
      stimulation with phytohemaglutenin (PHA) for 32 h. We report that addition of
      forskolin or cAMP analogues to the cells resulted in dephosphorylation of
      retinoblastoma protein commencing as early as 30 min. A rapid effect of forskolin
      was noted on the activity of cyclin-dependent kinase (cdk) 4, which decreased
      significantly within 30 min of treatment. The decrease in cdk4 activity was
      concurrent with reduced levels of cyclin D3 protein and a decrease in the
      fraction of cdk4 associated with cyclin D3. The down-regulation of cyclin D3 was
      at the level of translation, and this event was preceded by a pronounced
      inhibition of Akt/protein kinase B phosphorylation at Ser 473. Taken together,
      our data imply that cyclin D3 is a major effector of cAMP-mediated inhibition of
      cell cycle progression in PBL, and that cAMP exerts its effect on cyclin D3
      expression at the level of translation.

PMID- 10898515
TI  - IL-10 induces apoptosis in human monocytes involving the CD95 receptor/ligand
      pathway.
AB  - The cytokine IL-10 exerts potent immunosuppressive and anti-inflammatory effects,
      although the mechanisms of this action remain largely unknown. In the present
      study, we investigated the effects of IL-10 in human peripheral blood monocytes.
      We were able to demonstrate that IL-10 dose- and time-dependently triggers
      apoptosis in these cells as detected by annexin-V staining, the nick end labeling
      (TUNEL) procedure, electron microscopy and analysis of DNA laddering. IL-10
      induced apoptosis required the activation of proteases of the caspase family,
      since a peptide caspase inhibitor attenuated cell death and, in addition, the
      proteolytic activation of caspase-8 was observed. Since caspase-8 has been
      implicated as a regulator of apoptosis mediated by death receptors, we
      investigated a potential involvement of the CD95 receptor/ligand system. Indeed,
      treatment of monocytes with IL-10 induced a dose-dependent up-regulation of CD95
      receptor and ligand expression on the monocyte surface. Furthermore, a CD95
      ligand-neutralizing antibody significantly inhibited IL-10-induced apoptosis. In
      summary, our data show that IL-10 triggers monocyte apoptosis involving the CD95
      system via an autocrine or paracrine process. Therefore, at least part of the
      anti-inflammatory properties of IL-10 may involve induction of apoptosis in
      monocytes.

PMID- 10898516
TI  - Double mutant MRL-lpr/lpr-gld/gld cells fail to trigger lpr-graft-versus-host
      disease in syngeneic wild-type recipient mice, but can induce wild-type B cells
      to make autoantibody.
AB  - Lethally irradiated mice reconstituted with histocompatible stem cells from Fas
      deficient MRL/lpr mice develop a wasting syndrome reminiscent of chronic graft
      versus-host disease. However, reconstitution with double Fas-/Fas ligand (FasL)
      deficient stem cells does not result in wasting disease, demonstrating that FasL
      expression is an important component of the effector mechanisms leading to this
      syndrome. In the absence of wasting disease double-deficient T cells can induce
      wild-type B cells to make autoantibodies. These data indicate that autoantibody
      production is regulated by FasL-expressing T cells, and that Fas-sufficient wild
      type B cells differ from Fas-deficient Ipr cells only with regard to their
      sensitivity to FasL.

PMID- 10898517
TI  - Two YxxL segments of a single immunoreceptor tyrosine-based activation motif in
      the CD3zeta molecule differentially activate calcium mobilization and mitogen
      activated protein kinase family pathways.
AB  - Immunoreceptor tyrosine-based activation motifs (ITAM), consisting of two YxxL
      segments, transmit signals leading to IL-2 gene activation in T cells. We
      investigated here the functional difference in signal transduction between these
      two YxxL segments in the CD3zeta membrane-proximal ITAM. N-terminal YxxL mutants
      failed to induce ZAP-70 phosphorylation, elevation of intracellular Ca2+
      concentration ([Ca2+]i) or extracellular signal-regulated kinase (ERK) activation
      even in the presence of CD28 co-stimulation, whereas a mutant of the leucine
      residue at the C-terminal YxxL segment retained the ability to induce these
      events although this mutation abrogated the ability to induce IL-2 gene
      activation. In marked contrast to ERK activation, c-Jun N-terminal kinase (JNK)
      activation was observed in all mutants when co-stimulated with CD28. The mutant
      of the leucine residue at the C-terminal YxxL segment had a defect in the
      transcriptional activation at the NF-AT cis-element, which was restored to wild
      type level by addition of a Ca2+ ionophore, suggesting that the intensity and/or
      duration of [Ca2+]i elevation defines the threshold of T cell activation in this
      mutant. Our data collectively indicate that the activation pathways of ERK, JNK
      and Ca2+ mobilization are differentially regulated through YxxL segments of an
      ITAM.

PMID- 10898518
TI  - Control of epithelial Na+ conductance by the cystic fibrosis transmembrane
      conductance regulator.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial Cl-
      channel expressed in luminal membranes of secretory and reabsorptive epithelia.
      CFTR plays a predominant role in both cAMP- and Ca2+-activated secretion of
      electrolytes. Although Ca2+-dependent Cl- channels exist independent of CFTR in
      the airway epithelium, their physiological significance remains to be determined.
      However, CFTR seems to be the only relevant Cl- conductance in the colonic
      epithelium. Apart from its secretory function, CFTR also has a task in regulating
      the reabsorption of electrolytes by controlling the activity of the epithelial
      Na+ channel, ENaC. Accordingly, defects in CFTR causing the disease cystic
      fibrosis (CF) lead to disturbances of both the secretion and absorption of
      electrolytes. Therefore, it is unclear what is pathophysiologically more
      important for the development of CF lung disease, the impaired secretion of Cl-
      or the enhanced reabsorption of Na+ and consecutive hyperabsorption of
      electrolytes. The mechanisms of how CFTR and ENaC interact are unknown. Previous
      work has given rise to several interesting working hypothesis, such as direct
      protein interaction or interaction via cytoskeletal proteins. Recent studies
      demonstrate the importance of the first nucleotide binding fold of CFTR, not only
      for the inhibition of ENaC but also for the interaction with other ion channels.
      Further studies are required to demonstrate whether regulation of other ion
      channels and membrane transport by CFTR occur by a common mechanism.

PMID- 10898519
TI  - The very small-conductance K+ channel KvLQT1 and epithelial function.
AB  - KvLQT1 (KCNQ1) is a very small conductance K+ channel distributed widely in
      epithelial and non-epithelial tissues. Its specific biophysical and
      pharmacological properties are determined by the regulatory subunits IsK (KCNE1)
      and MiRP2 (KCNE3). In epithelial cells of the inner ear, pancreas, and airways it
      interacts with IsK to conduct a voltage-gated and slowly activating K+ current.
      In the colon it coassembles with KCNE3 to conduct an instantaneous and
      constitutively active K+ current. In Cl- secretory epithelia, such as the colon
      and pancreas, this K+ channel provides the driving force for Cl- exit and is
      located in the basolateral membrane. In the inner ear it enables luminal
      secretion of K+ into the endolymphatic space. The functional relevance of KvLQT1
      to epithelial function is revealed by blocking it pharmacologically or by
      studying animals with a genetic defect for it, which result in the breakdown of
      colonic Cl- secretion and endolymph production, respectively. KvLQT1 K+ channels
      are activated via cAMP or Ca2+ and inhibited by the chromanol 293B. Interaction
      with as yet unknown regulatory subunits may determine the properties of KvLQT1 in
      the rectal gland and other epithelial tissues in which KvLQT1 is not inhibited by
      chromanols.

PMID- 10898520
TI  - Effect of sulfhydryl reagents on the regulatory system of the L-type Ca channel
      in frog ventricular myocytes.
AB  - The effects of sulfhydryl (SH) reagents on the L-type Ca current (ICa) were
      studied in frog ventricular myocytes using the whole-cell patch-clamp method.
      Methanethiosulfonate ethylammonium (MTSEA+) was found to enter the cell through
      the membrane and cause a remarkable increase in Ica from the intracellular side.
      Methanethiosulfonate ethyltrimethylammonium (MTSET+) and methanethiosulfonate
      ethylsulfonate (MTSES-) could not penetrate the membrane and were effective only
      when directly applied to the intracellular side. In addition, suppressive effects
      on ICa of these MTS reagents were indicated by the following observation. A
      progressive decay in the peak amplitude of ICa after establishing maximal ICa,
      stimulated by intracellular MTSET+, was prevented by adding extracellular
      dithiothreitol (DTT). The SH-oxidizing agents N-ethylmaleimide (NEM), chloramine
      T (CL-T), 2,2'-dithiodipyridine (DTDP) and 2,2'-dithio-bis-5-nitropyridine
      (DTBNP) also exerted a stimulatory effect on Ica. The effect of SH reagents
      persisted even when cAMP production was inhibited with Rp-cAMP-S, or when G
      protein was inhibited with 1 mM GDPbetaS, indicating that the effect is not due
      to cAMP production or G-protein stimulation. It is concluded that there are sites
      on the Ca channels that are subject to direct modification by SH reagents.

PMID- 10898521
TI  - Spontaneous wheel running attenuates cardiovascular responses to stress in rats.
AB  - We investigated the effect of chronic, 10-week spontaneous wheel running (SWR)
      exercise on stress-induced cardiovascular responses in free-moving male rats,
      using a biotelemetry system. During cage-switch stress or immobilization stress,
      blood pressure and heart rate were significantly increased in both the SWR
      (P<0.001 for each stress) and control groups (P<0.001 for each stress). However
      the blood pressure response was attenuated significantly in the SWR group
      (P<0.001) during cage-switch stress, and the blood pressure and heart rate
      responses were attenuated significantly in the SWR group (P<0.0001 and 0.01,
      respectively) during immobilization stress. The plasma norepinephrine (NE)
      response induced by immobilization stress tended to be attenuated in the SWR
      group, but the groups showed no significant differences in the plasma NE and
      epinephrine (E) responses to both stresses. These results suggest that daily SWR
      in rats has beneficial effects in suppressing excessive blood pressure and heart
      rate responses induced by two different types of stress. The mechanisms
      responsible for the greater resistance to these stresses in the SWR rats should
      be investigated further.

PMID- 10898522
TI  - Nitric oxide synthesis causes inositol phosphate production and Ca2+ release in
      rat parotid acinar cells.
AB  - The activity of nitric oxide synthase (NOS) in rat parotid acinar cells was
      measured using a newly synthesized fluorescent NO indicator DAF-2/DA. Our results
      show that NO production is most effectively stimulated by activation of the beta
      adrenergic receptor, and to a minor extent by substance P (SP). NO activates the
      production of cGMP, an intracellular messenger that has been shown to release
      Ca2+ from ryanodine-sensitive intracellular stores. We found that cGMP is also
      able to release Ca2+ from ryanodine-insensitive intracellular stores. Our data
      show that a rise in the cGMP concentration induces inositol 1,4,5-trisphosphate
      [Ins(1,4,5)P3] synthesis and Ca2+ release from intracellular stores.

PMID- 10898523
TI  - Phenotypic changes in the composition of muscular fibres in rat soleus motor
      units after 14 days of hindlimb unloading.
AB  - The main goal of this study was to identify the different fibre types of the
      motor units (MUs) contained in the soleus muscles from control (CONT) rats and
      from rats submitted to 14 days of hindlimb unloading (HU). The MU types were
      classified according to their contractile properties and also using glycogen
      depletion followed by adenosine triphosphatase (ATPase) staining. In CONT rats,
      the soleus muscle contained two MU types identified as slow and fast types. After
      HU, the MU distribution showed three populations: slow, intermediate and fast.
      All the MUs from HU soleus were heterogeneous in terms of fibre type composition,
      indicating a complex remodelling of the muscle.

PMID- 10898524
TI  - Cyclic ADP-ribose induces a larger than normal calcium release in malignant
      hyperthermia-susceptible skeletal muscle fibers.
AB  - Malignant hyperthermia (MH) is associated with abnormal regulation of
      intracellular calcium in skeletal muscle fibers. Cyclic adenosine diphosphate
      ribose (cADPR) is an endogenous metabolite of beta-NAD+ that induces Ca2+ release
      from intracellular stores in many tissues. Microinjection of cADPR (0.5 or 1
      microM) increased the intracellular resting Ca2+ concentration ([Ca2+]i) in
      intact swine skeletal muscle in a dose-dependent manner. However, the increase in
      [Ca2+]i was greater in malignant-hyperthermia-susceptible (MHS) fibers than in
      non-susceptible (MHN) fibers. Incubation of muscle fibers in low external Ca2+
      solution or in the presence of L-type Ca2+ channel entry blockers, or
      intracellular microinjection of heparin or ruthenium red did not modify the
      effect of cADPR on [Ca2+]i. Dantrolene (50 microM), a known inhibitor of
      intracellular Ca2+ release, decreased resting [Ca2+]i and prevented the cADPR
      induced increase in [Ca2+]i. These results provide evidence: (1) for the
      existence of Ca2+ release mechanisms occurring via non-ryanodine or inositol
      1,4,5-trisphosphate (InsP3) receptor mechanisms; (2) that MHS skeletal muscles
      exhibit a higher responsiveness to cADP-ribose-induced release of Ca2+ and (3)
      that the ability of dantrolene to block cADP-ribose-induced release of Ca2+ could
      be related to its pharmacologic effect on resting [Ca2+]i.

PMID- 10898525
TI  - Muscarinic down-regulation of cAMP-stimulated potassium ion secretion by rabbit
      distal colon.
AB  - The sustained effects of the cholinergic agonist carbachol (CCh) on electrolyte
      transport across the isolated, short-circuited rabbit distal colon were examined
      in the absence and presence of secretagogue (di-butyryl cyclic-adenosine
      monophosphate, dB-cAMP). Steady-state, basal absorption of 22Na+, 42K+ (86Rb+),
      and 36Cl- were not significantly altered by addition of the CCh (10(-4) mmol/l)
      to the serosal reservoir. Stimulation with dB-cAMP (1.0 mmol/l, serosal) promoted
      K+ (or Rb+) and Cl- secretion across the colon, without significantly affecting
      the unidirectional or net fluxes of Na+. Serosal (but not mucosal) addition of
      CCh to dB-cAMP-stimulated tissues reduced the serosal to mucosal flux of Rb+
      (J(Rb)SM) in a concentration-dependent manner with a half-maximum concentration
      approximately equal 5 micromol/l. Pretreatment with CCh (100 micromol/l, serosal)
      inhibited dB-cAMP-induced K+ secretion, but had no significant effect on the
      steady-state unidirectional fluxes of Na+ or Cl-. Serosal histamine (20
      micromol/l) also inhibited J(Rb)SM in dB-cAMP-stimulated tissues. Serosal
      epinephrine (10 micromol/l) promoted a decrease in short-circuit current (Isc)
      and transepithelial potential (VT) that was mirrored by increases in J(Rb)SM.
      Both Isc, and VT became more positive and J(Rb)SM was reduced when CCh was added
      to the epinephrine-stimulated tissues. Serosal muscarine (50 micromol/l) mimicked
      the CCh-induced inhibition of J(Rb)SM, but serosal nicotine (50 micromol/l) had
      no effect. In atropine-treated tissues (1 micromol/l, serosal), CCh failed to
      block dB-cAMP-stimulated increases in J(Rb)SM. The inhibitory action of CCh was
      observed in tissues that had been pretreated with 50 micromol/l serosal
      hexamethonium (a ganglionic transmission blocker) or 2 micromol/l serosal
      tetrodotoxin (a voltage-gated Na+ channel blocker), indicating that the
      inhibitory action of this cholinergic agonist does not depend on remnant enteric
      neural pathways. Rubidium ion transport across confluent monolayers of T84 cells
      was similarly affected by dB-cAMP and CCh, supporting the notion that enteric
      neural pathways are not required. Serosal charybdotoxin (20 nmol/l) mitigated the
      inhibitory action of CCh on J(Rb)SM in dB-cAMP-stimulated tissues, suggesting a
      role for basolateral, Ca2+-dependent K+ channels in the actions of CCh. It is
      concluded that basolateral muscarinic receptors (and possibly other Ca2+
      dependent receptor pathways) of secretory colonocytes mediate the down-regulation
      of potassium ion secretion by rabbit distal colon, possibly by increasing
      basolateral membrane K+ conductance.

PMID- 10898526
TI  - Altered regulation of calcium channels and exocytosis in single human
      pheochromocytoma cells.
AB  - We established primary cultures of human pheochromocytoma chromaffin cells. We
      then tried to find what mechanism of their secretory apparatus could be altered
      to produce the massive release of catecholamines into the circulation and the
      subsequent hypertensive crisis observed in patients suffering this type of tumor.
      Their whole-cell Ca2+ channel currents could be pharmacologically separated into
      components similar to those found in normal human adrenal chromaffin cells: 20% L
      type, 30% N-type, and 50% P/Q-type Ca2+ channels. However, modulation of the
      channels by exogenous or endogenous ATP and opioids, via a G-protein membrane
      delimited pathway, was deeply altered; some cells having no modulation or very
      little modulation alternated with others having normal modulation. This may be
      the cause of the uncontrolled secretory response, measured amperometrically at
      the single-cell level. Some cells secreted for long time periods and were
      insensitive to nifedipine (L-type channel blocker) or to omega-conotoxin MVIIC
      (N/P/Q-type channel blocker), while others were highly sensitive to nifedipine
      and partially sensitive to omega-conotoxin MVIIC. Alteration of the
      autocrine/paracrine modulation of Ca2+ channels may lead to indiscriminate Ca2+
      entry and exacerbate catecholamine release responses in human pheochromocytoma
      cells.

PMID- 10898527
TI  - Altered gating of HERG potassium channels by cobalt and lanthanum.
AB  - Activation of the rapid, delayed rectifier K current (IKr) is important for
      normal repolarization of cardiac action potentials, especially in mammalian
      ventricular muscle. The study of this current has been greatly aided by the
      discovery that the human ether-a-go-go-related gene (HERG) encodes the pore
      forming alpha subunits of these channels. As for other voltage-activated K+
      channels, divalent and trivalent cations affect the gating of HERG channels by
      screening negative membrane surface charges or by direct interaction with the
      channel gating mechanism. Previous studies have reported that IKr of myocytes,
      and HERG channels heterologously expressed in Xenopus oocytes, are reduced by
      external Co2+ and La3+. We have reinvestigated the "blocking" effect of Co2+ and
      La3+ on HERG channels expressed in Xenopus oocytes. At concentrations previously
      reported to block IKr or HERG current (IHERG), Co2+ (10 mM) and La3+ (10 microM)
      had only small effects on the magnitude of fully activated IHERG. The apparent
      block results from altered kinetics and voltage dependence of gating, similar to
      the effects of Ca2+ on HERG channels. Under control conditions, the half-points
      for voltage-dependent activation and inactivation of HERG were -35+/-2.1 and 
      76.3+/-1.7 mV, respectively. Co2+ and La3+ accelerated the rate of deactivation,
      decreased the rate of current activation, and shifted the half-point of the HERG
      channel activation curve by +53 and +65 mV, respectively. Co2+ shifted the
      voltage dependence of inactivation by + 14 mV, whereas La3+ had no effect. Co2+
      also slowed the onset of IHERG inactivation and accelerated the rate of recovery
      from inactivation. These results indicate that reduction of IHERG by Co2+ (10 mM)
      and La3+ (10 microM) during depolarizing pulses is caused by a positive shift in
      the voltage dependence of activation, and does not result from pore block.

PMID- 10898528
TI  - The effect of heptanol on the electrical and contractile function of the
      isolated, perfused rabbit heart.
AB  - Changes in cardiac gap junction expression, such as those following myocardial
      infarction and produced in connexin knockout mice, are associated with a
      predisposition to arrhythmias. The present experiments investigated the effects
      of heptanol, a reversible gap junction inhibitor, on isolated Langendorff
      perfused rabbit hearts. The introduction and withdrawal of heptanol inhibited
      both pressure generation and electrical conduction. These effects were completely
      reversible. Possible mechanisms for these findings were investigated through
      measurement of the concentration dependence of heptanol's effects upon conduction
      velocity and repolarization duration. Low concentrations of heptanol (less than
      0.3 mM) caused small but significant increases in the delay between the stimulus
      (delivered to the basal septum) artefact and local activation of the left
      ventricle, as measured from bipolar electrogram (BEG) recordings. There was a
      steep increase in the latency between stimulus and left-ventricular activation at
      concentrations of heptanol above 0.3 mM. These findings are explicable by earlier
      reports of heptanol actions on gap junctions in vitro and modelling studies of
      the effects of reduced gap junction conductance on conduction velocity. Heptanol
      decreased repolarization duration, measured from the activation recovery interval
      (ARI) of BEGs, and monophasic action potential duration at 70% repolarization
      (MAPD70). Heptanol also reduced left-ventricular developed pressure (LVDP), and
      the maximum rates of contraction and relaxation of the left ventricle; these
      effects were concentration dependent and reversible. However, changes in ARIs,
      LVDP and the maximum rates of change of pressure lacked the steep response to 0.3
      1.0 mM heptanol shown by the latency. These other effects are therefore likely to
      be mediated by cellular targets other than gap junctions. Perfusion of hearts
      with heptanol was also associated with a high incidence of arrhythmias. During
      premature stimulation protocols arrhythmias could be induced in hearts perfused
      with 0.1-0.3 mM heptanol but not at higher concentrations. This suggests that
      there is a critical range of slowed conduction that permits the development of re
      entrant arrhythmias in the normal heart, although the effects of heptanol on
      repolarization duration may also contribute to its pro-arrhythmic activity.

PMID- 10898529
TI  - K+ currents activated by leukotriene D4 or osmotic swelling in Ehrlich ascites
      tumour cells.
AB  - K+ and Cl- currents activated by hypoosmotic cell swelling (IK,vol and Icl,vol)
      or after addition of leukotriene D4 (LTD4) to cells in isotonic medium were
      studied in Ehrlich ascites tumour cells. IK,vol and Icl,vol were not affected by
      strong buffering of intracellular Ca2+ or by additional removal of extracellular
      Ca2+. In isotonic media, 5 nmol/l LTD4 activated large K+ but not Cl- currents.
      The LTD4-activated IK was, as has been shown previously for IK,vol, insensitive
      to charybdotoxin (ChTX) but was blocked by the antiarrhythmic drug clofilium. The
      current/voltage (I/V) relation for the LTD4-activated IK was, as recently
      demonstrated for IK,vol, well fitted by the Goldman-Hodgkin-Katz current equation
      between -130 mV and 30 mV in both physiological and K+-rich extracellular
      solutions. LTD4 had no additional effect on the magnitude of IK in Ehrlich cells
      already activated by the hypoosmotic stimulus. Nevertheless, the onset time for
      IK after hypoosmotic cell swelling was significantly less in the presence of
      LTD4. The similar I/V relation, pharmacological sensitivity and lack of
      additivity suggest that hypoosmotic swelling and addition of LTD4 activate the
      same K+ channels in Ehrlich cells. The influence of [Ca2+]i appears, however, to
      differ between IK,vol and the IK activated by LTD4 in that the latter was reduced
      significantly by strong buffering of [Ca2+]i. This might reflect the involvement
      of some additional factor in the hypoosmotic activation of K+ channels besides
      the stimulation mediated by LTD4.

PMID- 10898530
TI  - Effect of urea and osmotic cell shrinkage on Ca2+ entry and contraction of
      vascular smooth muscle cells.
AB  - The present study was performed to elucidate the effects of urea on vascular
      smooth muscle cells (SMC). Addition of urea (20, 50, 100 mM) to physiological
      salt solution blunted the vasoconstrictory effect of phenylephrine (by 17, 25 and
      30%, respectively) and of an increased extracellular K+ concentration (by 7, 14
      and 19%, respectively) without affecting the basal tone of rabbit arterial rings.
      According to Fura-2 fluorescence in cultured SMC (A7r5), urea had no effect on
      basal intracellular calcium activity ([Ca2+]i), but significantly blunted the
      increase of [Ca2+]i following an increase of extracellular K+. Whole-cell patch
      clamp studies revealed that the Ca2+ current through voltage-sensitive Ca2+
      channels is significantly inhibited in the presence of urea. As evident from
      calcein fluorescence, addition of urea leads to sustained cell shrinkage. The
      effects of urea on vascular tone, [Ca2+]i activity, voltage-gated Ca2+ channels
      and cell volume are mimicked by addition of raffinose or NaCl. However, the cell
      shrinkage induced by urea is sustained, whereas the addition of equiosmolar NaCl
      is only transient and followed by a regulatory cell volume increase. Moreover,
      hypertonic NaCl increases, whereas urea decreases, the transcription of cell
      volume-regulated kinase hsgk. In conclusion, urea leads to sustained shrinkage of
      vascular smooth muscle cells, which is followed by inhibition of voltage-gated
      Ca2+ channels, a decrease of [Ca2+]i and thus blunts the vasoconstrictory action
      of phenylephrine and increased extracellular K+ concentration.

PMID- 10898531
TI  - Ischemia/reperfusion-induced changes in intracellular free Ca2+ levels in rat
      skeletal muscle fibers--an in vivo study.
AB  - Accumulation of intracellular free calcium (Ca2+i) may play an essential role in
      the ischemia/reperfusion injury of skeletal muscle. Although it has been shown
      that Ca2+i levels significantly increase during ischemia/reperfusion, it is still
      a matter of debate whether Ca2+i increases during ischemia alone. It was the aim
      of this study to monitor the in vivo Ca2+i levels in the rat spinotrapezius
      muscle during ischemia of varying duration and reperfusion, using a ratiometric
      fluorescence technique, and to investigate the relationship between the
      postischemic flow patterns and Ca2+i, if any. The muscle was loaded with Indo
      1/AM and imaged by a cooled digital camera. Pre- and postischemic tissue
      perfusion was assessed by means of an analogue camera. Our results show that
      short-term ischemia (5, 15 and 30 min) and subsequent reperfusion (60 min) does
      not alter Ca2+i homeostasis and that tissue perfusion promptly recovers after the
      insult. One or two hours of ischemia resulted in changes in Ca2+i levels, varying
      from preparation to preparation; increases in some and no changes in others. In
      these preparations three distinct flow patterns - normal, compromised and no
      reflow - could be distinguished during the 60-min reperfusion. Our main
      conclusion is that in skeletal muscle Ca2+i levels may increase, the increase
      probably depending on the muscle fiber type exposed.

PMID- 10898532
TI  - Aminoguanidine reduces brain lesion volume after cold injury in the rat.
AB  - The aim of this study was to examine the effect of aminoguanidine (AG), which is
      thought to be an inducible nitric oxide synthase (iNOS) inhibitor, on lesion
      volume induced by cold injury in the parietal cortex of the rat. Cold lesion was
      induced by applying a precooled (-78 degrees C) copper cylinder (diameter: 3 mm)
      for 6 s to the intact dura. Lesion volume was determined using the
      triphenyltetrazolium-chloride method after 24 h. Pretreatment (1 h) and
      posttreatment (7.5 h) with AG [10 or 100 mg/kg body mass (BM)] reduced the lesion
      volume by 15 and 27%, respectively. However, posttreatment alone with AG (10 and
      100 mg/kg BM) caused less of a reduction in lesion volume, by 8 and 20%,
      respectively. Pre- and posttreatment with AG also reduced the plasma
      nitrate/nitrite concentration compared with lesioned, saline-treated rats. Only a
      double therapy with AG (100 mg/kg BM) resulted in a significant reduction (48%)
      compared to saline alone, which was even larger (55%) compared to the sham group.
      The tissue nitrate/ nitrite concentration was significantly attenuated by pre-
      and posttreatment with AG (100 mg/kg BM) not only in the ipsilateral but also in
      the contralateral hemisphere. There was no difference regarding the parameter
      between shams and lesioned, saline-treated rats. Since combined pre- and
      posttreatment with AG reduced the lesion volume more than posttreatment alone and
      the plasma and tissue nitrate/nitrite concentrations were diminished during AG
      therapy compared to shams, we hypothesize that AG inhibits not only iNOS but also
      other enzymes, such as nNOS, diamine oxidase, and advanced glycation endproducts
      synthase.

PMID- 10898533
TI  - The effects of inhibiting myosin light chain kinase on contraction and calcium
      signalling in human and rat myometrium.
AB  - The effect of inhibiting myosin light chain kinase on contractions of human and
      rat myometrium has been investigated, to determine whether force can be produced
      independently of myosin phosphorylation. Two inhibitors were used, wortmannin and
      ML-9, and their effects on spontaneous, high-K-depolarization-induced and
      oxytocin-induced force studied. Both inhibitors reduced and then abolished
      uterine force, irrespective of how it was produced; this was the case for both
      human and rat myometrium, and pregnant and non-pregnant tissue. The effects of
      wortmannin on intracellular [Ca2+] and inward Ca2+ current were examined. The
      data showed that the reduction in force produced by wortmannin occurs without a
      reduction of either the Ca2+ current or [Ca2+]. It is concluded that, under
      normal physiological conditions, myosin light chain kinase phosphorylation of
      myosin is essential for uterine force production and that there is little or no
      role for alternative force-producing pathways.

PMID- 10898534
TI  - Simultaneous patch-clamp recording and calcium imaging in a rhythmically active
      neuronal network in the brainstem slice preparation from mouse.
AB  - Intracellular calcium signals are critical for modulation of neuronal function,
      and also for pathophysiological states during human neurodegenerative disease,
      such as Morbus Alzheimer and amyotrophic lateral sclerosis (ALS). We investigated
      intracellular calcium signals in motoneurones of the nucleus hypoglossus from the
      mouse, which were maintained in a functionally intact state of rhythmic,
      respiratory-related activity. Simultaneous patch-clamp recordings and calcium
      imaging demonstrated that rhythmic inspiratory-related clusters of action
      potential (AP) discharges are paralleled by calcium oscillations both in somatic
      and dendritic compartments. Calcium oscillations resulted primarily from the AP
      induced opening of voltage-dependent calcium channels in the soma and dendrites.
      Dendritic calcium transients differed from somatic responses in their kinetics,
      amplitude, voltage dependence and regulation of basal calcium levels. Based on a
      combination of infrared differential interference contrast optics,
      microfluorimetric calcium imaging and electrophysiological patch-clamp
      recordings, our results demonstrate that the brainstem slice preparation is an
      attractive model system to study the integration and superposition of calcium
      signals in a functionally intact neuronal net.

PMID- 10898535
TI  - The Federation of European Physiological Societies (FEPS). Are physiologists
      ready for new physiology?

PMID- 10898536
TI  - Cisplatin resistance and oncogenes--a review.
AB  - Cisplatin is among the most widely used broadly active cytotoxic anticancer
      drugs; however, its clinical efficacy is often limited by primary or the
      development of secondary resistance. Several mechanisms have been implicated in
      cisplatin resistance, including reduced drug uptake, increased cellular
      thiol/folate levels and increased DNA repair. More recently, additional pathways
      have been characterized indicating that altered expression of oncogenes that
      subsequently limit the formation of cisplatin-DNA adducts and activate anti
      apoptotic pathways may also contribute to the resistance phenotype. Several lines
      of evidence suggest that expression of ras oncogenes can confer resistance to
      cisplatin by reducing drug uptake and increasing DNA repair; however, this is not
      a uniform finding. Tumor cells, in contrast to normal cells, respond to cisplatin
      exposure with transient gene expression to protect or repair their chromosomes.
      The c-fos/AP-1 complex, a master switch for turning on other genes in response to
      DNA-damaging agents, has been shown to play a major role in cisplatin resistance.
      In addition, AP-2 transcription factors, modulated by protein kinase A, are also
      implicated in cisplatin resistance by regulating genes encoding for DNA
      polymerase beta and metallothionines. Furthermore, considerable evidence
      indicates that mutated p53 plays a significant role in the development of
      cisplatin resistance since several genes implicated in drug resistance and
      apoptosis (e.g. mismatch repair, bcl-2, high mobility group proteins, DNA
      polymerases alpha and beta, PCNA, and insulin-like growth factor) are known to be
      regulated by the p53 oncoprotein. Improved understanding of molecular factors for
      the development of cisplatin resistance may allow the prediction of clinical
      response to cisplatin-based treatment. Furthermore, the identification of
      oncogenes involved in cisplatin resistance has already led to in vitro approaches
      which successfully inactivated these genes using ribozymes or antisense
      oligodeoxynucleotides, thus restoring cisplatin sensitivity. It is conceivable
      that these strategies, once transferred to a clinical setting, may have the
      potential to enhance the efficacy of cisplatin against a great variety of
      malignancies and thus more fully exploit the antineoplastic and curative
      potential of this drug.

PMID- 10898537
TI  - Plasma pharmacokinetics of etoposide (VP-16) after i.v. administration to
      children.
AB  - The pharmacokinetics of etoposide (VP-16), a semi-synthetic derivative of
      podophyllotoxin, were studied in 16 pediatric patients (median age 8.3 years;
      range 4 months to 22 years) including two girls with Down's syndrome (DS). The
      drug was administered as infusions (1-3 h) in a wide range of doses (9-322 mg,
      corresponding to 32-210 mg/m2). The area under the plasma concentration versus
      time curve (AUC), dose normalized by the body surface area, was independent of
      age, while AUC normalized by the dose in mg/kg increased with increasing age of
      the patients. The interpatient variability of AUC, normalized for the dose in
      mg/m2, was 23% (CV) compared to 32% (CV) normalized for the dose in mg/kg. The
      terminal half-life time was 4.1 h (median value; range 2.0-7.8 h). The
      pharmacokinetics of etoposide in children with DS and chromosomally normal
      children were very similar with regard to systemic drug exposure and plasma half
      life time. From the pharmacokinetic point of view it was therefore not necessary
      to make any dose modifications in the two girls with DS. The two DS patients did
      not experience any enhanced degree of toxicity from their etoposide treatments.
      The results support that dosing of etoposide to children should be based on body
      surface area.

PMID- 10898538
TI  - Scintillation autofluorographic assessment of isotope uptake in human glioma
      cells grown on microtitration plates using sodium salicylate.
AB  - We describe a simple method for detecting [35S]methionine-labeled protein in
      fixed human astrocytoma cells grown in 96-well microtitration plates using a
      modified scintillation autofluorographic method. Following isotopic labeling,
      cells are fixed in situ and a solution of salicylic acid in methanol is dried
      onto the cell layer. The fluorographic image is detected using blue-sensitive X
      ray film attached to the base of the plate which, following development, can be
      quantitated using a scanning densitometer. The relationship between cell number
      and optical density is linear, and there is a close correlation between the dose
      response curves generated by this method and alternative isotopic detection
      methods and cell counting. This assay provides a suitable alternative to the use
      of potentially toxic scintillation fluids based on organic solvents like toluene
      or xylene in chemosensitivity testing of human brain tumors.

PMID- 10898539
TI  - Docetaxel in 253 previously treated patients with progressive locally advanced or
      metastatic breast cancer: results of a compassionate use program in The
      Netherlands.
AB  - The aims of this study were to evaluate the efficacy and safety of docetaxel
      (Taxotere) in patients with progressive locally advanced or metastatic breast
      cancer, previously treated with at least one chemotherapy regimen, and the effect
      of the number of previous chemotherapy lines on response rate, progression-free
      survival and overall survival. Two-hundred and fifty-three patients from 10
      hospitals in The Netherlands received docetaxel as part of a compassionate use
      program. The majority had received prior anthracycline-containing chemotherapy
      (84.2%). The recommended starting dose was 100 mg/m2 i.v. every 3 weeks. All
      patients received corticosteroid premedication. Two-hundred and thirty patients
      were evaluable for response. The overall response rates (ORR) to docetaxel when
      used as second-, third- or fourth-line treatment were, respectively, 40.2, 26.0
      and 34.6% (p value 0.30). The median progression-free survival for this
      population was 4.9 months and the median overall survival of the whole group was
      8.5 months, and both were not related to the number of previous chemotherapy
      regimens (p value, respectively, 0.71 and 0.16). The toxicity of docetaxel was
      manageable and neutropenia was the most frequently noted toxicity. This study
      confirms that docetaxel is an active cytotoxic agent in pretreated patients with
      progressive locally advanced or metastatic breast cancer and is still active when
      used as third- or fourth-line treatment.

PMID- 10898540
TI  - Docetaxel and irinotecan (CPT-11) in the treatment of malignant pleural
      mesothelioma--a feasibility study.
AB  - We chose to treat malignant pleural mesothelioma with a combination of docetaxel
      and irinotecan (CPT-11), because there have been preliminary reports that CPT-11
      is active against mesothelioma, and docetaxel and CPT-11 were the most active
      agents in our in vitro experiments in human mesothelioma cell lines. Fifteen
      previously untreated patients with pleural mesothelioma (IMIG Stage III-IV) were
      given docetaxel 60 mg/m2 followed by CPT-11 190 mg/m2 on day 1, repeated every 3
      weeks. All the patients were evaluable for toxicity and 13 patients were
      evaluated for response. No objective responses (complete or partial) were
      achieved, but there were two minor responses (overall response rate 15%) each of
      a duration of 4 months. Three patients had stable disease (23%); median time to
      progression was 7 months. Median survival in all the patients was 8.5 months from
      the first chemotherapy cycle and 11 months from diagnosis. Toxicity was severe
      with seven of 15 patients suffering neutropenic fever and six of 15 patients
      grade 3-4 diarrhea. The trial was discontinued because of toxicity and lack of
      activity. We do not recommend the combination of docetaxel and CPT-11 using the
      schedule presented here for further investigation in malignant mesothelioma.
      However, CPT-11 and docetaxel, individually, still warrant further study in this
      disease, especially in combination with cisplatin.

PMID- 10898541
TI  - Dramatic tumor response of bulky liver metastases following treatment with CPT-11
      and a chronomodulated 4-day infusion of 5-fluorouracil, folinic acid and
      oxaliplatin every 2 weeks in a colorectal cancer patient.
AB  - Three active antitumor agents, i.e. 5-fluorouracil (5-FU), oxaliplatin and CPT
      11, are available for the treatment of advanced colorectal cancer (CRC) patients
      and have been successfully combined in two-drug regimens. Hence, CRC has become a
      chemosensitive disease, but the optimal combination of these agents in first-line
      treatment remains to be determined. We report the first case of the combination
      of CPT-11 with oxaliplatin, 5-FU and folinic acid (FA) as first-line chemotherapy
      for a patient with a pre-occlusive sigmoid adenocarcinoma and synchronous bulky
      liver metastases. CPT-11 was given at 125 mg/m2, prior to the start of a
      chronomodulated 4-day infusion of oxaliplatin 25 mg/m2/day, 5-FU 800 mg/m2/day
      and FA 300 mg/m2/day repeated every 2 weeks. The doses could be escalated to 150
      mg/m2 for CPT-11 and 900 mg/m2/day for 5-FU. After six cycles of chemotherapy 70%
      reduction in tumor size was documented in the liver. The primary tumor was no
      longer detectable by barium enema. The toxicity included three episodes of grade
      4 neutropenic fever, and two episodes of severe diarrhea and vomiting with
      dehydration. A cumulative grade 2 neurosensory toxicity was observed after six
      cycles. Following surgery of the primary tumor, because of the major hepatic
      tumor response and of the absence of extra-hepatic metastases, the patient might
      be registered for a liver transplantation program. This first report of combining
      the three active agents in CRC every 2 weeks led to a high dose intensity of each
      agent and was associated with a dramatic tumor response of a very advanced
      disease in a patient with already altered performance status. The antitumor
      activity in this patient suggests that a three-drug intensified regimen might be
      feasible and active. A prospective study appears warranted to further examine the
      efficacy and toxicity of this therapeutic approach, and to determine whether it
      may increase the fraction of advanced CRC patients becoming resectable. This
      aggressive chemotherapy program may contribute to a re-examination of the
      usefulness of liver transplantation in patients with metastatic CRC confined to
      the liver.

PMID- 10898542
TI  - Intra-arterial mitoxantrone and paclitaxel in a patient with Stewart-Treves
      syndrome: selection of chemotherapy by an ex vivo ATP-based chemosensitivity
      assay.
AB  - We report on a 72-year-old patient developing Stewart-Treves syndrome (STS) of
      the right arm 9 years after curative irradiation for ipsilateral stage III breast
      cancer. Facing the poor track record of both irradiation and chemotherapy in this
      highly malignant lymphangiosarcoma, amputation was recommended but refused by the
      patient. Therefore, limb conserving-therapy using three courses of intra-arterial
      mitoxantrone (MX) and paclitaxel (PTX) was attempted. This novel chemotherapy
      protocol was selected by pretherapeutic ex vivo ATP-based chemosensitivity
      testing of autologous tumor tissue. The patient experienced complete response,
      which was subsequent histologically confirmed by compartment resection. When
      developing recurrent STS outside of the perfused area 6 months after primary
      therapy, the patient was retested and reinduced with three other courses of
      intraarterial MX/PTX which again produced durable complete remission. This case
      demonstrates the benefit of indivdualized therapy in this prognostically
      desperate disease allowing both limb conservation and maintained quality of life.

PMID- 10898543
TI  - Effective treatment of a patient with a high-grade endometrial stromal sarcoma
      with an accelerated regimen of carboplatin and paclitaxel.
AB  - The rarity of endometrial stromal sarcoma (ESS) and its poor response to
      treatment provides fertile ground for investigational therapies. An accelerated
      regimen of carboplatin and paclitaxel is investigated. A patient with a recent
      history of treated tuberculosis of the lung represented with infertility and
      acute abdominal pain from suspected fibroids, and underwent a laparotomy with a
      diagnosis of a high-grade ESS. A novel therapeutic approach using a regimen of
      carboplatin and paclitaxel with the reinfusion of filgrastim-mobilized peripheral
      blood progenitor cells is described. A partial response was observed following
      six cycles of chemotherapy. Grade IV thrombocytopenia occurred after the last
      cycle, with recovery prior to pelvic radiotherapy. The patient remained well 1
      year post-diagnosis. High-grade ESS is responsive to combination chemotherapy
      with paclitaxel and carboplatin, and requires further evaluation. The use of an
      accelerated regimen may also have contributed to the response and this question
      awaits randomized trials.

PMID- 10898544
TI  - Colon carcinoma with synchronous ovarian metastasis--report and discussion of
      five cases.
AB  - Ovarian metastasis may present at the time of initial diagnosis of colon
      carcinoma or as a later recurrence. Little meaningful information is available
      regarding the treatment and outcome of synchronous ovarian metastasis of colon
      carcinoma. This report describes the clinical course of five patients with
      synchronous ovarian metastasis of colon carcinoma who were treated with
      aggressive surgery and chemotherapy. The treatment consisted of maximal surgical
      debulking followed by systemic chemotherapy with weekly 24 h infusion of high
      dose 5-fluorouracil and leucovorin. All of the five patients had subsequent
      disease-free periods ranging from 6 to 43+ months following operation. Two of the
      patients who had no or minimal peritoneal involvement were still alive without
      disease at 33 and 43 months. The data from these cases suggest that aggressive
      surgery and systemic chemotherapy may be highly efficacious in the treatment of
      colon carcinoma with synchronous ovarian metastasis. Maximal debulking followed
      by chemotherapy may be particularly effective in those patients with minimal
      peritoneal involvement.

PMID- 10898545
TI  - Modulation of dihydrofolate reductase gene expression in methotrexate-resistant
      human leukemia CCRF-CEM/E cells by antisense oligonucleotides.
AB  - An increase in the cellular levels of dihydrofolate reductase (DHFR) is one of
      the most common mechanisms of tumor resistance to methotrexate (MTX), an
      antimetabolite that is widely used in the treatment of a variety of human
      malignancies. The MTX-resistant phenotype generally occurs as a consequence of
      DHFR gene amplification which in turn is responsible for DHFR gene
      overexpression. We have designed antisense oligodeoxynucleotides (aODNs) against
      the DHFR mRNA and tested their in vitro effect on human leukemia CCRF-CEM/E
      cells, overexpressing the DHFR gene about 20-fold in comparison with the CCRF
      CEM/S parental cell line. An aODN complementary to a region encompassing the AUG
      translation start (DHFR1) of DHFR mRNA and a mixture of two aODNs complementary
      to the 5' untranslated region (DHFR2+DHFR3) have been used. A DHFR1 scrambled
      sequence ODN and a fully degenerated ODN were the controls. All ODNs had a
      phosphodiester backbone. DHFR1 and the relevant scrambled ODN were also capped
      with two phosphorothioate derivatives at both the 5' and 3' ends in order to
      increase ODN stability against serum nucleases. ODNs were vehiculated with a
      cationic lipid, N-[1-(dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate
      (DOTAP), known to enhance ODN cell uptake and biological activity. The effects of
      ODNs on DHFR gene expression were studied after a 4 day treatment by measuring
      both DHFR mRNA levels, using a semi-quantitative reverse transcription polymerase
      chain reaction method, and DHFR protein levels by flow cytometry. A marked
      reduction in DHFR mRNA levels (79.7 and 74.2%, respectively) was observed with
      both DHFR1 and DHFR2+DHFR3 aODNs, associated with a lower decrease in DHFR enzyme
      (44.8 and 61%, respectively). aODN effects on MTX cytotoxicity in CCRF-CEM/E
      cells were also assessed. No marked enhancement of in vitro MTX cytotoxicity was
      observed following co-exposure of cells with aODNs and the tested concentrations
      of the antifol (0.05 and 0.5 microM), indicating that no substantial reversal of
      the MTX-resistant phenotype was induced by the study aODNs.

PMID- 10898546
TI  - Resistance to paclitaxel induces time-delayed multinucleation and DNA
      fragmentation into large fragments in MCF-7 human breast adenocarcinoma cells.
AB  - DNA fragmentation was investigated in MCF7 and the MCF7TAX19 paclitaxel-resistant
      subline exposed to paclitaxel for 24 h. No nucleosome-sized DNA fragmentation was
      observed by DNA agarose gel electrophoresis in both cell lines. However, DNA
      fragmentation was detected by flow cytometry sub-G1 peak analysis in both cell
      lines immediately after paclitaxel exposure. Nuclear abnormalities were observed
      in both cell lines in the range of 35-40% of the total cell population. This
      value was reached immediately in MCF7 cells but was time-delayed in MCF7TAX19
      cells. Significant morphologic differences were observed between sensitive and
      resistant cell lines, 24 h after exposure to 50 nmol/l paclitaxel. Although no
      difference in the sub-G1 cell population was observed between sensitive and
      resistant cells, a significantly higher rate of multinucleated cell features was
      observed in resistant cells.

PMID- 10898547
TI  - Decreased cortisol secretion by adrenal glands perfused with the P-glycoprotein
      inhibitor valspodar and mitotane or doxorubicin.
AB  - The aim of this study was to investigate the role of P-glycoprotein (P-gp) in the
      adrenal gland. It has been presumed that P-gp, rather than being involved in
      physiological cortisol secretion, plays a role in protecting the adrenacortical
      cells from xenobiotics. To explore this a study was performed on perfused bovine
      adrenal glands. Individual experimental groups were perfused with either a
      selective P-gp blocker (valspodar) alone, with a xenobiotic (mitotane or
      doxorubicin) alone or with both valspodar and a xenobiotic. The cumulative
      amounts of cortisol secreted in each individual group were calculated and the two
      sample t-test was used to compare the mean values of cumulative amounts. The mean
      value of cortisol secreted from the group of adrenals perfused with the P-gp
      blocker was not significantly different from that of the control group. Treatment
      with either mitotane or doxorubicin decreased the amount of cortisol secreted but
      not significantly when compared to the amount of cortisol secreted in basal
      conditions. However, treatment with the P-gp blocker valspodar in addition to
      either mitotane or doxorubicin significantly decreased cortisol secreted compared
      to the amount of cortisol secreted by the glands treated with either mitotane
      (p=0.009) or doxorubicin (p=0.017) alone. The regressive changes discovered in
      all experimental groups were most prominent when valspodar was used with either
      mitotane or doxorubicin. We found that P-gp blockade increases by xenobiotic
      (mitotane and doxorubicin)-induced damage of adrenocortical cells, which points
      to a role of P-gp in the protection of adrenal gland from xenobiotics.

PMID- 10898548
TI  - Incomplete Freund's adjuvant reduces diabetes in the non-obese diabetic mouse.
AB  - As the study of type 1 diabetes moves towards preventive therapy, the role of
      adjuvants needs to be addressed. Incomplete Freund's adjuvant (IFA) is thought of
      as "immunologically inert" as, unlike complete FA (CFA), it has no components
      designed to provoke an immune response. We investigated the effect of IFA as an
      immunomodulator on the disease process leading to type 1 diabetes in the non
      obese diabetic (NOD) mouse. 24 NOD mice were injected intradermally (i.d.) at 8
      and 12 weeks of age with a 1:1 mixture of IFA and saline; 24 controls received
      saline alone. Splenocytes were tested against antigens thought to be involved in
      the disease process, namely insulin, a GAD peptide, a beta-casein peptide, a Glut
      2 peptide and concanavalin A (ConA) as a non-specific antigen. In the IFA
      experiment diabetes incidence was 13% compared to 38% in the controls (p < 0.05).
      In vitro, splenocytes from IFA treated animals showed non-specific
      immunosuppression with ConA (p < 0.01), whereas the response to 1-casein and Glut
      2 was raised in IFA treated animals with respect to controls. ELISA using
      supernatants from IFA treated animals, showed a typical Th2 cytokine pattern,
      whereas controls showed a Th1 pattern. In conclusion, IFA alone can reduce
      diabetes incidence in the NOD mouse apparently by modulating the immune response
      towards beta-cell related specific antigens. As IFA has been adopted as an
      adjuvant in preventive trials in the NOD mouse, this might have implications for
      the interpretation of previous and future results.

PMID- 10898549
TI  - Insulin-like growth factor 1-induced alterations in lumbospinal monoamine
      dynamics.
AB  - A wealth of evidence indicates that insulin-like growth factor (IGF-1) is
      involved in neurotransmitter release, synaptic plasticity, morphogenesis and
      regulation of gene expression. RT-PCR and immunocytochemical-based techniques
      revealed that IGF-1 and its receptor are highly expressed by different neuronal
      elements of the spinal cord lumbar enlargement. Accordingly, the present study
      intended to examine lumbospinal monoamine dynamics in the context of the
      neurotrophic factor IGF-1. Spinal release of norepinephrine (NE) represented by 3
      methoxy-4-hydroxyphenylglycol (MHPG)/NE ratio was enhanced by IGF-1. This action
      of IGF-1 was associated with a similar increase in both tyrosine hydroxylase (TH)
      immunoreactivity and the level of its mRNA. In contrast, neuronal contents of
      serotonin and its metabolite 5-hydroxyindoleacetic acid in IGF-1-treated animals
      remained at control level. Genistein, a tyrosine kinase inhibitor, which by
      itself had no effect on NE metabolism, abolished the induction effect of IGF-1 on
      TH and MHPG/NE ratio. Our results suggest that IGF-1 augments the lumbospinal
      noradrenergic system by an intracellular mechanism involving a receptor-linked
      tyrosine kinase. The physiological consequences of the IGF-1 actions are
      discussed in terms of neuroprotection and nociception.

PMID- 10898550
TI  - Analysis of ultrashort feedback regulation in human placenta: synthesis and
      secretion of GnRH by human trophoblastic cells.
AB  - BACKGROUND: Gonadotropin-releasing hormone (GnRH) presumably controls placental
      growth and functions by autocrine/paracrine mechanisms, and is therefore an
      important part of the neuroendocrine network in human placenta. AIM: Our earlier
      work had indicated that GnRH was expressed in human placenta; in extension to
      these findings, we wanted to analyse synthesis and release of GnRH by
      trophoblastic cells. GnRH-associated peptide, co-linearly synthesised with GnRH,
      was used as indicator of actual peptide synthesis. METHOD: First, we immunised
      rabbits with lipopeptides containing partial sequences of GnRH-associated peptide
      (GAP) and developed antibodies for immunohistochemical staining. Second, we set
      up a competitive enzyme immunoassay to measure GnRH: Non-biotinylated GnRH, GnRH
      analogues or trophoblastic cell culture supernatants were used to inhibit binding
      of biotinylated des-pGlu1-GnRH to a monoclonal anti-GnRH antibody. RESULTS: a)
      Placental sections stained positive for GAP in the layers of trophoblastic cells.
      b) GnRH could be detect by a competitive EIA in supernatants of placental
      cultures in concentrations between 200 and 5 nM. CONCLUSIONS: GnRH is synthesised
      and released by trophoblastic cells.

PMID- 10898551
TI  - Results of a two-year treatment with slow release lanreotide in acromegaly.
AB  - In this open sequential study we evaluated the long-term effectiveness and
      tolerability of the i.m. administration of slow release lanreotide 30 mg (SRL) in
      18 acromegalics (7 M/11 F, age 50.9+/-12.7 yr). Baseline mean GH and IGF-1 levels
      were 15.8+/-6.6 ng/ml and 702+/-74 ng/ml, respectively. Four hours, 1, 7, and 14
      days after SRL, mean GH levels were 8.9+/-5.9 (p < 0.005), 11.4+/-6.9 (p < 0.05),
      9.1+/-4.5 (p < 0.05), and 9.1+/-4.1 ng/ml (p < 0.05), respectively; and the IGF-1
      values at 1, 7, and 14 days were 624+/-77 (p < 0.05), 555+/-83 (p < 0.001), and
      467+/-58 ng/ml (p < 0.0001), respectively. Four hours after SRL administration GH
      was < 2.5 ng/ml in 11 patients and decreased 85% of the basal value, without
      normalizing, in another case. In the following 2 weeks, 7 and 2 patients
      maintained GH < 2.5 ng/ ml or < 50% of baseline; 3 and 2 of them attained IGF-1
      values in the normal range or < 50% of basal levels. A patient developed acute
      pancreatitis after the injection of the drug and therefore stopped the treatment.
      Another patient did not continue SRL, and she was turned on octreotide, s.c.
      administered (OCT), because only the latter treatment ameliorated significantly
      the headache. In 16/18 patients the treatment was continued until the 24th month.
      SRL was administered every 14 days until the 24th month in 3 cases, whereas in 13
      patients the dose schedule was increased every 10 days since the 7th month
      because they did not normalize serum GH and IGF-1 levels. In these 16 patients
      baseline GH and IGF-1 levels were 10.0+/-2.5 ng/ml and 671+/-75 ng/ml,
      respectively. At the 1st, 3rd, and 6th month of treatment mean GH levels fell to
      5.4+/-1.4 (p < 0.05), 5.3+/-1.8 (p < 0.05), and 5.0+/-1.6 (p < 0.05) ng/ml,
      respectively; and IGF-1 declined to 511+/-87 (p < 0.005), 565+/-85 (p < 0.05),
      and 525+/-94 (p < 0.01) ng/ml, respectively. Throughout the first semester GH was
      < 2.5 ng/ml in 5 patients and decreased > 50% in another three. IGF-1 levels
      normalized in 3/5. Throughout the following 18 months of treatment, mean GH
      (3.4+/-1.0 ng/ml) and IGF-1 (413+/-75 ng/ml) values decreased significantly in
      comparison with both the baseline concentrations (GH p < 0.01, IGF-1 p < 0.001)
      and the levels measured during the 1st semester of treatment (GH p < 0.05, IGF-1
      p < 0.001). GH remained < 2.5 ng/ml in 11 patients, and in 8/11 cases IGF-1 fell
      in the normal range. Serum GH and IGF-1 levels decreased by more than 50% of
      baseline levels in 2 other cases. At MRI, pituitary adenoma was no longer evident
      in one patient previously treated with OCT and significantly decreased in another
      patient previously treated with surgery plus radiotherapy, as well as in a
      patient previously untreated. During treatment the percentage of patients
      complaining of headache and fatigue decreased significantly (chi2, p < 0.05 and p
      < 0.0005, respectively). Overall, the headache (p < 0.005), arthralgia (p <
      0.05), and paresthesia (p < 0.01) ameliorated significantly. Ultrasound scan
      showed gallbladder sludge or sand-like stones in 5/11 patients. This study, which
      is one of the longest surveys on a relatively large series of acromegalics
      treated with SRL, confirms the long-term effectiveness of this drug for the
      treatment of patients with active acromegaly. SRL decreases significantly GH and
      IGF-1 in most cases and induces the shrinkage of the pituitary tumor in some
      patients previously either untreated or both treated for acromegaly. SRL improves
      significantly clinical symptoms and it is well tolerated.

PMID- 10898552
TI  - A 60 minute hyperglycemic clamp is sufficient to assess both phases of insulin
      secretion.
AB  - The hyperglycemic clamp is considered to be the gold standard for determining
      both first and second phase insulin secretion. In order to achieve a reasonable
      insulin plateau for the second phase, it has become common practice to clamp for
      120 or even 180 minutes at 10 mM. It is unknown whether earlier insulin
      determinations would be sufficient to predict second phase insulin secretion. We
      therefore reviewed the hyperglycemic clamp data of 58 subjects with different
      degrees of glucose tolerance to assess whether one or more insulin concentrations
      determined at earlier time points of the clamp could predict second phase insulin
      secretion (insulin and C-peptide concentration at 120 minutes). The correlation
      coefficients between second-phase insulin secretion and plasma insulin or C
      peptide at 60 min were 0.95 and 0.96, respectively (both p<0.00005). Averaging
      plasma insulin or C-peptide over 2 or more adjacent time points did not improve
      the correlation. In conclusion, a one-hour hyperglycemic clamp can provide the
      standard measurement of first phase insulin secretion plus a good approximation
      of second phase insulin secretion.

PMID- 10898553
TI  - Effects of early protein restriction and adult obesity on rat pancreatic hormone
      content and glucose tolerance.
AB  - Rats were fed a diet containing either 20% ("control") or 8% ("reduced-protein")
      protein throughout pregnancy and lactation. Their female offspring were weaned
      onto the same respective diets. At 63 days of age one set of control and reduced
      protein rats (n = 16 per group) underwent intraperitoneal glucose tolerance tests
      and one week later were killed and their pancreatic hormones extracted and
      measured. The reduced protein rats had better glucose tolerance (p < 0.001) and
      lower pancreatic insulin (p < 0.01) and amylin (p < 0.01) contents. Further sets
      of control and reduced-protein rats were then fed either chow or a cafeteria
      style diet (n = 16 in each of the four groups). These rats underwent
      intraperitoneal glucose tolerance tests at 133 days of age, which showed the
      cafeteria-fed animals to have a worse glucose tolerance than the chow-fed animals
      irrespective of previous diet exposure (p < 0.0001). One week later reduced
      protein rats still had lower pancreatic insulin contents (p < 0.05) (and a trend
      for lower amylin contents), but also had increased pancreatic glucagon contents
      (p < 0.05). There were no detectable differences in pancreatic somatostatin-like
      immunoreactivity or pancreatic polypeptide contents. These results are consistent
      with pancreatic beta- and alpha-cells being selectively susceptible to effects
      associated with early dietary protein restriction.

PMID- 10898554
TI  - Food-related sensory stimuli are able to promote pancreatic polypeptide elevation
      without evident cephalic phase insulin secretion in human obesity.
AB  - The data concerning the cephalic phase of insulin secretion (CPIS) in human
      obesity are controversial. We investigated the effect of a variety of sensory
      challenges on CPIS in 17 non-diabetic obese patients (four males, 13 females,
      mean age 41.1 years, mean BMI 38.7). Water, saccharin, and lemon juice were used
      as oral stimuli, and a complete meal was simply presented as visual and olfactory
      stimulations. Twelve healthy normal-weight subjects (four men, eight women, mean
      age 39.9, mean BMI 22.5) also underwent oral stimulation as controls, and the
      patients who underwent the sight and smell stimulations were also tested for
      pancreatic polypeptide (PP) changes in order to verify the occurrence of truly
      cephalic reflex during the test. Insulin levels were measured before and after
      each stimulation (every min for the first 5 min, and then after 10, 20, and 30
      min). None of the stimuli (saccharin, lemon juice or water retained in the mouth
      for 2 min and were then spat out; the combined and separate sight and smell of a
      meal for 2 min) led to a significant increase in insulin in the obese patients
      (except in the case of one woman after oral stimulation). The oral stimuli led to
      a variable CPIS in one female and three male controls. Despite the absence of
      CPIS, the five obese patients undergoing all three sensory stimulations related
      to the meal (combined sight and smell, sight alone and smell alone) showed an
      early and significant increase in plasma PP concentrations within the first 3
      min; this was more pronounced after the combined than after the separate
      exposure. Although only preliminary, these results underline the variability but
      substantial lack of CPIS in obese patients, thus suggesting that it can be
      considered a relatively rare and unrelevant event even in the presence of a true
      brain-mediated reflex revealed by the rapid and consistent increase in PP found
      in our experiments.

PMID- 10898555
TI  - Oleoyl-estrone lowers the body weight of both ob/ob and db/db mice.
AB  - Homozygous obese db/db (BKS-Lepr(db) and ob/ob (B6-Lep(ob)) mice were treated for
      14 days with a continuous infusion of a fat emulsion (controls) or loaded with
      oleoyl-estrone at doses of 12.5 and 50 nmol/g x d using surgically inserted
      osmotic minipumps. Treatment with oleoyl-estrone resulted in a marked decrease in
      body weight in both strains, compared with the unchecked growth of controls. In
      db/db mice, plasma urea and insulin, as well as liver lipid decreased with
      treatment. In ob/ob mice, the effect on insulin was more marked, in parallel with
      higher plasma lipids pointing to increased fat mobilisation. The results suggest
      that oleoyl-estrone effects on body fat reserves and insulin resistance are not
      mediated by leptin, since ob/ob mice lack this hormone and in the db/db it is
      present but cannot induce effects because of defective leptin receptors; in both
      cases oleoyl-estrone treatment lowers body weight.

PMID- 10898556
TI  - The American Association for Cancer Education: factors relating to the
      participation and growth of membership.

PMID- 10898557
TI  - Topic selection in undergraduate medical education and relevance to general
      practice.
AB  - Most patients who have possibly malignant diseases are first seen by physicians
      not specifically trained in oncology. The cancer education that undergraduate
      medical students receive is frequently dominated by basic science topics,
      detailed staging data, pharmacology of cancer drugs, and treatment protocols.
      This is not in accordance with the needs in general practice. In pre-course
      information and correspondence with reference to the International Summer School
      "Oncology for Medical Students," held in Groningen, The Netherlands, it is
      emphasized that the Summer School focuses on cancer care in general practice. As
      part of the education program participants are required to prepare abstracts and
      posters on oncologic topics in general health care in their own countries.
      Despite the emphasis on cancer care in general practice and despite suggestions
      for topics, some students have first sent in abstracts describing basic sciences
      research projects. Evidently during their medical training the relevancy of
      cancer education to the reality of daily practice had not been taught or had
      already been lost. In teaching undergraduate medical students, it should be
      realized that the vast majority will choose non-oncology disciplines. Thus,
      cancer education of these students should focus mainly on clinical cancer issues
      that are relevant in general practice.

PMID- 10898558
TI  - Oral cancer education training methods: a comparison of self-study and didactic
      approaches.
AB  - BACKGROUND: Dentists' competence and comfort level in detecting oral cancer may
      be strongly influenced by their dental school training. The purpose of this study
      was to compare the demonstrated knowledge of oral cancer topics among students
      receiving lectures and those learning the material through self-instruction at
      two dental schools. METHODS: Students at School 1 received 17 hours of lectures
      on various topics in oral cancer, including epidemiology, etiologic factors,
      histopathology, clinical appearance, clinical management and treatment, and oral
      complications. Lecture topics reflected material in the assigned text. Students
      at School 2 received only an introductory lecture, followed by a ten-week self
      paced course using the same text used in School 1. At the end of the courses, the
      students at the two schools received identical 50-item final examinations.
      RESULTS: The students who had received the lectures and assigned readings scored
      significantly higher than did those assigned self-instruction alone (mean score
      of 91.2% vs 81.3%; p < 0.0001). This difference remained after statistical
      adjustment for entering grade-point average and Dental Aptitude Test score.
      CONCLUSIONS: Self-study of assigned readings may result in lower levels of
      knowledge of oral cancer topics than more traditional lecture-based teaching. The
      impact of this difference on clinical performance has not yet been demonstrated.

PMID- 10898559
TI  - Controversy about mammography screening guidelines and physician practices at a
      university medical center.
AB  - To determine the effect of the 1994 controversy about mammography screening
      guidelines on physicians' practices, the authors surveyed primary care physicians
      at a university medical center in 1995. The 44-item survey elicited information
      about screening practices for women in four age groups, at the time of the study
      and five years earlier. High screening rates were maintained for the
      noncontroversial 50+ age group, but baseline mammography was still being ordered
      for 30-39-year-olds. Women 40-49 years old as well as older women were being
      screened less often in 1995.

PMID- 10898560
TI  - Preconsultation education promoting breast cancer screening: does the choice of
      media make a difference?
AB  - BACKGROUND: Multimedia technology can be a valuable resource for health promotion
      and patient education initiatives because it allows messages to be presented
      within an environment that is both sensory-rich and interactive (i.e., the user
      can explore the information according to his or her particular needs and
      interests). Using clinic waiting time as an opportunity for breast cancer
      education, this investigation examined whether an educational intervention
      promoting breast cancer screening would be more effective when using interactive
      multimedia than when using written materials. METHODS: Over a five-month period,
      108 women (40-70 years of age) from two clinics (a family practice clinic and a
      free clinic for the poor) participated in the study. Participants initially
      completed measures assessing perceptions of the personal importance of breast
      cancer, knowledge, and anxiety about screening procedures. They then were
      randomly assigned to receive breast cancer education by using an interactive
      multimedia program or by reading a brochure. Following the intervention, the
      participants once again completed the perceived importance, knowledge, and
      anxiety measures, and evaluated the educational materials. RESULTS: These women
      perceived breast cancer to be a more personally important health issue, learned
      more, and reported less anxiety about cancer screening following the intervention
      regardless of method. Younger women learned more from the educational materials
      than did older women. Although the multimedia program received more favorable
      evaluations than the brochure, this effect was mediated by the message
      recipient's age, as younger women responded more favorably to the multimedia
      materials than did older women. CONCLUSION: Preconsultation education is a
      valuable but rarely used opportunity to promote breast cancer screening. If well
      constructed, educational materials using a variety of media can be effective.
      While preferences for media may in part depend on the audience's age,
      considerably more research is needed to better understand how the interplay of
      media, message, and audience characteristics can help accomplish health-promotion
      objectives.

PMID- 10898561
TI  - "5 A Day" achievement badge for urban boy scouts: formative evaluation results.
AB  - BACKGROUND: Certain cancers are more common among African Americans (AA). Fruit
      and vegetables (F&V) reduce cancer risk, but Americans, and African Americans in
      particular, do not meet the "5 A Day" goal. Scouting organizations, particularly
      urban Boy Scout groups that target inner-city youth, provide promising channels
      for nutritional behavioral change programs. METHODS: Focus groups were conducted
      with urban Boy Scouts and their parents to identify factors influencing F&V
      consumption and evaluate potential intervention activities. Twenty-four-hour
      dietary recalls were collected from 85 area Boy Scouts. A national data set was
      used to obtain values for F&V consumption by African American and European
      American (boys age 0-16). RESULTS: Vegetable preferences were low and a negative
      peer influence for vegetables was reported. The group has limited food
      preparation skills, but both parents and scouts reported that F&V were available
      in their homes. Use of goal setting and use of problem-solving techniques were
      limited. The local scouts' mean F&V intake was 3.2 servings per day. Ethnic
      differences in F&V consumption were identified in the national data. CONCLUSIONS:
      Based on these results and previous interventions in schools, an overall
      structure for the intervention was developed to include eight weekly troop
      sessions and two camping sessions, parent newsletters, seven weekly home badge
      assignments, and ten comic books.

PMID- 10898562
TI  - Design of "High 5": a school-based study to promote fruit and vegetable
      consumption for reduction of cancer risk.
AB  - BACKGROUND: This paper describes the methods used in "High 5," a school-based
      study to increase fruit and vegetable consumption for cancer risk reduction.
      METHODS: Twenty-eight elementary schools were matched and randomized to
      intervention or control conditions. All students were assessed based on diet and
      psychosocial variables at baseline and one and two years post-baseline. The
      intervention included classroom, parent, and environmental components. RESULTS:
      The study recruited 1,698 families and retained 85%. The two conditions were
      equivalent at baseline; 50% female students, 81% to 84% European-American
      students, and 2.9 servings of fruit and vegetables per day. Good completion was
      achieved across the intervention components (e.g., 90% of lessons taught, 72% of
      parent materials read, 3.6 servings of fruit and vegetables offered in
      cafeterias). CONCLUSIONS: The use of school-based programs, with strong
      evaluation designs, will enhance knowledge about the modification of nutrition
      behavior and cancer risk in children. Lessons learned from the study are
      reported.

PMID- 10898563
TI  - Site specific 1:1 opioid:albumin conjugate with in vitro activity and long in
      vivo duration.
AB  - A site-specific 1:1 dynorphin A-(1-13)-NH(2) derivative conjugated specifically
      to Cys 34 on human serum albumin (CCI-1035) was shown to be an opioid receptor
      agonist in vitro and to be a long lasting antinociceptive agent when administered
      intravenously to mice as assessed by an acetic acid writhing assay. When 10
      micromol/kg of CCI-1035 was administered to mice, rapid antinociception was
      observed within 5 min following intravenous bolus injection and was sustained
      beyond 8 h. Antinociceptive activity was absent in a heat induced pain model
      using a mouse tail-flick assay. This finding represents the first report of a 1:1
      albumin opioid conjugate retaining potent in vivo activity equal to or greater
      than dynorphin A, accompanied by a dramatic extension in duration of action. This
      novel site-specific bioconjugation technology produces an agent that may be
      useful for peripheral pain therapy.

PMID- 10898564
TI  - Synthesis of base-substituted dUTP analogues carrying a photoreactive group and
      their application to study human replication protein A.
AB  - Analogues of dUTP bearing a photoreactive 2-nitro-5-azidobenzoyl (NAB) group
      linked via spacers of varying length (n = 2, 4, 7-13 atoms) to the 5-position of
      the uridine ring (NAB-n-dUTP) were synthesized and characterized. DNA polymerase
      beta efficiently incorporated these analogues into synthetic primer-template
      substrates in place of TTP, which allowed us to selectively introduce a
      photoreactive group at the 3' primer terminus. After completing photoreactive
      primer synthesis, the reaction mixtures were irradiated with monochromatic UV
      light (315 nm) in the presence of human replication protein A (RPA), a
      heterotrimer consisting of three subunits with molecular mass 70 kDa (p70), 32
      kDa (p32), and 14 kDa (p14), and were separated by SDS-PAGE. The photoreactive
      primers cross-linked directly with p70 and p32, but cross-linking of p14 was not
      achieved even by varying the length of the spacer group. The data speak in favor
      of the protection of p14 by other RPA subunits from the interaction with 3'-end
      of the primer. Cross-linking of substrates to pol beta is inhibited when the
      analogue bears a short spacer (n = 2, 4, 7, and 8), but this is abrogated
      somewhat when longer spacers (n = 9-13) are examined. On the basis of these
      observations, we suggest that RPA and pol beta form a complex on primer-template
      substrates.

PMID- 10898565
TI  - Enhanced targeting specificity to tumor cells by simultaneous recognition of two
      antigens.
AB  - Radioimmunotherapy recently afforded convincing results for B-cell non-Hodgkin's
      lymphoma treatment with antibody specific for B-cell differentiation antigens.
      High doses of unlabeled or labeled antibodies are necessary to saturate specific
      sites on normal B-cells. We thus developed a new targeting strategy, taking
      advantage of dual binding cooperativity, to enhance the specificity of the
      radioactive uptake by tumor cells. This approach was evaluated using human
      Burkitt lymphoma cells (Ramos) which express both CD10 and CD20 antigens. Most
      normal cells express at most one of these two differentiation antigens but many
      hematological tumors, including most human B type acute lymphoblastic leukemia
      cells, express both. Cells pretargeted with two bispecific antibodies, one
      recognizing CD10 and a histamine derivative (HSG), the other recognizing CD20 and
      the DTPA-indium complex, bind cooperatively radiolabeled mixed-haptens (DTPA
      HSG). Increased binding (about 5-fold compared to binding to only one of CD10 or
      CD20 antigens) is observed at 37 degrees C, demonstrating the feasibility of the
      technique. This binding enhancement is a slow process, not observed at 4 degrees
      C. Such a binding enhancement will increase specificity for targeting isotopes to
      double antigen positive tumor cells compared to nontumor tissue cells bearing
      only one of them. This approach might be used to increase tumor irradiation with
      minimal irradiation of normal cells.

PMID- 10898566
TI  - Permeability of yeast cell envelope to fluorescent galactosylated telomers
      derived from THAM.
AB  - The work reported herein deals with the study of cellular recognition and
      permeability phenomena in yeasts. Various galactosylated organic telomers derived
      from trishydroxymethyl-aminomethane (THAM) and bearing fluorescent moieties were
      synthesized in order to measure their ability to cross the yeast cell envelope.
      Grafting fluorescent probes on the organic telomer backbone allowed us to study
      their specific behaviors toward the yeasts by fluorescence microscopy. Yeasts
      belonging to the genera Kluyveromyces and Saccharomyces were used for this study.
      With Saccharomyces yeast cells bearing mannose-specific lectins or lectin-like
      proteins, on their outer surface, all the galactosylated or nongalactosylated
      organic telomers passed through the cell envelope and invaded the cytoplasm. With
      Kluyveromyces yeast cells bearing galactose-specific lectins, the galactosylated
      organic telomers were blocked at the outer surface while the nongalactosylated
      derivatives crossed the cell envelope. Moreover, preincubation of Kluyveromyces
      yeasts with galactose or methylgalactose inhibited the cell surface anchorage of
      the organic telomers and allowed their penetration into the cytoplasm. When
      assays were performed on spheroplasts of both Kluyveromyces and Saccharomyces
      yeasts, no fixation on the surface could be observed, and all the derivatives
      went through the membrane and invaded the cytoplasm.

PMID- 10898567
TI  - Conjugation and modeled structure/function analysis of lysozyme on glycine
      esterified cotton cellulose-fibers.
AB  - The antimicrobial activity of lysozyme covalently bound to glycine-derivatized
      cotton cellulose was assessed in a 96-well format. Lysozyme was immobilized on
      glycine-bound cotton through a carbodiimide reaction. The attachment to cotton
      fibers was made through both a single glycine and a glycine dipeptide esterified
      to cotton cellulose. Higher levels of lysozyme incorporation were evident in the
      diglycine-linked cotton cellulose samples. The antibacterial activity of the
      lysozyme-conjugated cotton cellulose against Bacillus subtilis was assessed as a
      suspension of pulverized cotton fibers in microtiter wells. Inhibition of B.
      subtilis growth was observed to be optimal within a range of 0.14-0.3 mM
      (equivalent to 4-20 mg of lysozyme-bound cotton/mL) of lysozyme. Enhancement of
      activity over soluble lysozyme may result from the solid-phase protection
      afforded by the cellulose linkage of the glycoprotein against proteolytic lysis.
      Computational models of lysozyme based on its crystal structure attached through
      aspartate, glutamate, and COOH-terminal residues to cellopentaose-(3) Gly-O-6
      glycyl-glycine ester were constructed. The models demonstrate no steric
      constraints to the active-site cleft from the glycine-conjugated cellulose chain
      when lysozyme is bound at the carboxylates of Asp-87, Glu-7, Asp-119, Asp-18, and
      COOH-terminal Leu-129. The more robust antibacterial activity of the enzyme when
      bonded to cotton fibers suggests good potential for biologically active enzymes
      on cotton-based fabrics.

PMID- 10898568
TI  - Photochemical immobilization of anthraquinone conjugated oligonucleotides and PCR
      amplicons on solid surfaces.
AB  - Ligand immobilization on solid surfaces is an essential step in fields such as
      diagnostics, bio sensor manufacturing, and new material sciences in general. In
      this paper a photochemical approach based on anthraquinone as the chromophore is
      presented. Photochemical procedures offer special advantages as they are able to
      generate highly reactive species in an orientation specific manner. As presented
      here, anthraquinone (AQ) mediated covalent DNA immobilization appears to be
      superior to currently known procedures. A synthetic procedure providing AQ
      phosphoramidites is presented. These reagents facilitate AQ conjugation during
      routine DNA synthesis, thus enabling the AQ-oligonucleotides to be immobilized in
      a very convenient and efficient manner. AQ-conjugated PCR primers can be used
      directly in PCR. When the PCR is performed in solution, the amplicons can be
      immobilized after the PCR. Moreover, when the primers are immobilized prior to
      the PCR, a solid-phase PCR can be performed and the amplicons are thus produced
      directly on the solid support.

PMID- 10898569
TI  - Conjugation of epitope peptides with SH group to branched chain polymeric
      polypeptides via Cys(Npys).
AB  - Since bioconjugates may play an important role as therapeutics in the future, the
      development of new and effective conjugation strategies is necessary. For the
      attachment of peptide-like molecules to carriers, there are two main coupling
      methods involving amide or disulfide bonds. Conjugation through an amide bond can
      be achieved in several well-defined ways known from peptide chemistry. However,
      the formation of disulfide bridges between cysteine-containing peptides and
      carrier molecules still has some problems. In this paper, we describe a novel
      approach in which the carrier polypeptide is modified by 3-nitro-2
      pyridinesulfenyl (Npys)-protected cysteine and this derivative has been applied
      for conjugation of Cys-containing epitope peptides with poly(L-lysine)-based
      branched polypeptides. Considering the stability of Npys group in the presence of
      pentafluorophenol, Boc-Cys(Npys)-OPfp dervivative was selected for introduction
      to the N-terminal of branches of polypeptides backbone. The branches of the
      polymers were built up from oligo(DL-alanine) (poly[Lys(DL-Ala(m))], AK) and
      elongated by an optically active amino acid [poly[Lys(X(i)-DL-Ala(m))], XAK]. We
      found that the nature of X (Glu, Ser, Thr) has great influence on the
      incorporation of the protected cysteine residue. Herpes simplex virus and
      adenovirus epitope peptides were conjugated to Boc-Cys(Npys)-modified
      polypeptides. Results indicate that the incorporation of epitope peptides depends
      on the number of Npys group on the polymers as well as on the presence/absence of
      Boc-protecting group on the Cys residue. This new class of Cys(Npys)-derivatized
      branched polypeptides is stable for a couple of months and suitable for effective
      preparation of epitope peptide conjugates possessing increased water solubility.

PMID- 10898570
TI  - Steric stabilization of poly-L-Lysine/DNA complexes by the covalent attachment of
      semitelechelic poly[N-(2-hydroxypropyl)methacrylamide].
AB  - The concept of steric stabilization was utilized for self-assembling
      polyelectrolyte poly-L-lysine/DNA (pLL/DNA) complexes using covalent attachment
      of semitelechelic poly[N-(2-hydroxypropyl)methacrylamide] (pHPMA). We have
      examined the effect of coating of the complexes with pHPMA on their
      physicochemical stability, phagocytic uptake in vitro, and biodistribution in
      vivo. The coated complexes showed stability against aggregation in 0.15 M NaCl
      and reduced binding of albumin, chosen as a model for the study of the
      interactions of the complexes with plasma proteins. The presence of coating pHPMA
      had no effect on the morphology of the complexes as shown by transmission
      electron microscopy. However, results of the study of polyelectrolyte exchange
      reactions with heparin and pLL suggested decreased stability of the coated
      complexes in these types of reactions compared to uncoated pLL/DNA complexes.
      Coated complexes showed decreased phagocytic capture by mouse peritoneal
      macrophages in vitro. Decreased phagocytosis in vitro, however, did not correlate
      with results of in vivo study in mice showing no reduction in the liver uptake
      and no increase in the circulation times in the blood. We propose that the rapid
      plasma elimination of coated pLL/DNA complexes is a result of binding serum
      proteins and also of their low stability toward polyelectrolyte exchange
      reactions as a consequence of their equilibrium nature.

PMID- 10898571
TI  - Transglutaminase-mediated dual and site-specific incorporation of poly(ethylene
      glycol) derivatives into a chimeric interleukin-2.
AB  - To expand the applications of poly(ethylene glycol) (PEG)-protein conjugates for
      clinical use, we have developed a novel method for dual and site-specific
      incorporations of PEG derivatives into proteins using a substrate peptide
      (AQQIVM, named TG2) and transglutaminase (TGase). In our previous studies, TG2
      was shown to be a special peptide with two adjacent Gln substrates for guinea pig
      liver transglutaminase (G-TGase). We have now constructed a chimeric protein
      (named rTG2-IL-2) of human interleukin-2 (IL-2), in which TG2 was fused to the N
      terminus of IL-2. For the G-TGase-catalyzed reaction, rTG2-IL-2 was dually and
      site-specifically modified with alkylamine derivatives of PEG (PEG10, average
      M(r) 10 kDa) at both the Gln2 and Gln3 residues in the appended tag. To
      demonstrate the effectiveness of the G-TGase-catalyzed PEG-incorporation, we have
      compared the characteristics and the biological properties of PEG10-rTG2-IL-2
      species with two PEG10 molecules attached to rTG2-IL-2 [(PEG10)(2)-rTG2-IL-2]
      with that of (PEG10)(2)-rhIL-2(R), in which PEG10 was randomly incorporated into
      rhIL-2 by a general procedure using a N-hydroxysuccinimidyl ester of PEG (PEG10
      COOSu) (M(r) 10 kDa). (PEG10)(2)-rTG2-IL-2 was found to be superior in its in
      vitro bioactivities and equivalent in its pharmacokinetic profiles to (PEG10)(2)
      rhIL-2(R). Unlike most previous methods, this approach can place dual PEG chains
      at designed sites on chimeric proteins without decreasing their bioactivities.
      Thus, TGase-catalyzed PEG-incorporation would improve the therapeutic utility of
      PEG-protein conjugates.

PMID- 10898572
TI  - Synthesis, conjugation, and radiolabeling of a novel bifunctional chelating agent
      for (225)Ac radioimmunotherapy applications.
AB  - 225Ac (t(1/2) = 10 days) is an alternative alpha-emitter that has been proposed
      for radioimmunotherapy (RIT) due to its many favorable properties, such as half
      life and mode of decay. The factor limiting use of (225)Ac in RIT is the lack of
      an acceptably stable chelate for in vivo applications. Herein is described the
      first reported bifunctional chelate for (225)Ac that has been evaluated for
      stability for in vivo applications. The detailed synthesis of a bifunctional
      chelating agent 2-(4-isothiocyanatobenzyl)-1,4,7,10,13, 16-hexaazacyclohexadecane
      1,4,7,10,13,16-hexaacetic acid (HEHA-NCS) is reported. This ligand was
      conjugated to three monoclonal antibodies, CC49, T101, and BL-3 with chelate-to
      protein ratios between 1.4 and 2. The three conjugates were radiolabeled with
      (225)Ac, and serum stability study of the [(225)Ac]BL-3-HEHA conjugate was
      performed.

PMID- 10898573
TI  - Mechanism of intermolecular purine-purine-pyrimidine triple helix stabilization
      by comb-type polylysine graft copolymer at physiologic potassium concentration.
AB  - We previously reported a novel strategy to stabilize purine motif triplex DNA
      within a mammalian gene promoter at physiologically relevant pH, temperature, and
      potassium (K(+)) concentrations by a comb-type poly(L-lysine)-graft-dextran
      copolymer [Ferdous et al., (1998) Nucleic Acids Res. 26, 3949-3954]. Here we
      describe the major contribution(s) of the copolymer to stabilize the purine motif
      triplex DNA at physiological K(+) concentrations. Self-aggregation through
      guanine-quartet formation of guanine-rich (G-rich) triplex-forming
      oligonucleotides (TFOs) has long been proposed for K(+)-mediated inhibition of
      the purine motif triplex formation. However, this was not the case for the severe
      inhibitory effect of K(+) observed under our reaction conditions. Rather
      significant decrease in rate of triplex formation involving a G-rich TFO was a
      major factor to confer K(+) inhibition. Interestingly, in the presence of the
      copolymer the rate of triplex formation was tremendously increased and K(+)
      induced dissociation of preformed triplexes was not observed. Moreover, the
      triplex-promoting/stabilizing efficiency of the copolymer was amazingly higher
      than that of physiological concentrations of spermine. An absolute increase in
      binding constant of the TFO to the target duplex could therefore be the
      predominant mechanistic source for the copolymer-mediated triplex stabilization
      under physiological conditions in vitro.

PMID- 10898575
TI  - Synthesis and characterization of a sulfhydryl-reactive rhenium metal-ligand
      complex.
AB  - We describe the synthesis and spectral characterization of a rhenium metal-ligand
      complex. This complex reacts with sulfhydryl groups via an iodoacetamide side
      chain on the phenanthroline ligand and displays a high limiting anisotropy near
      0.35 when excited at 442 nm. When covalently linked to human serum albumin, this
      complex displayed a mean decay time of about 1 micros. This decay time is
      appropriate for measuring rotational correlation times on the microsecond time
      scale as may occur for large macromolecular complexes.

PMID- 10898574
TI  - In vivo transchelation of copper-64 from TETA-octreotide to superoxide dismutase
      in rat liver.
AB  - An understanding of the metabolic fate of radiometal-labeled peptides is
      important due to their application in the areas of diagnostic imaging and
      targeted radiotherapy. Radioisotopes of copper ((64)Cu, T(1/2) = 12.7 h; (67)Cu,
      T(1/2) = 62 h) have been labeled to monoclonal antibodies (mAbs) and peptides and
      have applications in the areas of PET imaging and targeted radiotherapy of
      cancer. Copper-64-TETA-D-Phe(1)-octreotide ([(64)Cu]TETA-OC) has been shown to
      bind to the somatostatin receptor, both in vitro and in vivo, and this agent
      inhibited the growth of somatostatin-receptor positive tumors in rats. Copper-64
      TETA-OC, however, showed a retention of activity in the blood, liver, and bone
      marrow, suggesting possible dissociation of (64)Cu from TETA-OC in vivo. The
      purpose of this study was to determine if (64)Cu dissociates from [(64)Cu]TETA-OC
      and binds to the protein, superoxide dismutase (SOD) in rat liver. The liver
      metabolism of [(64)Cu]TETA-OC was examined in normal rats using a gel
      electrophoresis assay specific for SOD and size-exclusion chromatography. The
      major metabolite in rat liver at 20 h postinjection had a molecular weight of 32
      kDa as shown by size-exclusion chromatography. A gel electrophoresis assay
      specific for the detection of SOD [nitro-blue tetrazolium (NBT)] showed that a
      (64)Cu-labeled protein isolated from rat liver homogenates comigrated with SOD.
      Evaluating the metabolic fate of copper radiopharmaceuticals demonstrated that
      Cu(II) dissociates from macrocyclic chelators such as TETA and binds to proteins
      in high concentrations, namely SOD in rat liver.

PMID- 10898576
TI  - Concepts for the syntheses of biotinylated steroids. Part II: 17beta-estradiol
      derivatives as immunochemical probes.
AB  - Biotinylated 17beta-estradiol (E2) derivatives are helpful probes for a better
      understanding of biospecific E2 interactions with steroid-binding proteins such
      as the estrogen receptor and anti-steroid antibodies. We describe synthetic
      strategies for the biotinylation of E2 toward the 3, 6alpha, and 7alpha positions
      using biotinyl-N-hydroxysuccinimide esters with different spacers, varying in
      structure and chain length. Key reaction for biotinylation at the 3 position is
      the regioselective ether formation of the phenolate E2 anion with a linker
      mesylate without protecting the 17beta-hydroxyl group. The 6alpha position is
      accessible via a 3,17beta protected 6alpha-hydroxy E2, prepared by stereospecific
      sodium borohydride reduction of 6-oxo E2. Direct cyanoethylation of the alcohol
      followed by reduction to the amine allows the biotinylation to 6alpha-O-coupled
      cyanoethyloxy linker E2 derivatives. Alternatively, 6alpha-O-coupled
      cyanoalkyloxy polyether linker E2 probes are obtained by a Williamson ether
      synthesis of the alcohol precursor with omega-t-butyl-dimethylsilyloxy-5-oxa
      nonylmesylate. Cyanoethylation of the desilylated compound and further reduction
      of the nitrile led to the terminal amine. Reductive amination of the 3, 17beta
      acetylated 6-oxo E2 compound with 6-cyanoethyloxyhexyl ammonium acetate yields in
      a mixture of 6alpha/beta-N-alkylated E2 nitriles. The epimers are separated by
      reversed-phase HPLC and the 6alpha-compound subsequently reduced to the terminal
      amine. The 7alpha-biotinylated E2 compound is derived from 7alpha-(11'-undecyl-N
      methyl-N-butylamide) E2, which is already known from literature. Subsequently,
      the 3 and 17beta positions are protected, and the amide is reduced to the 7alpha
      (11'-undecanol) compound. Further cyanoethylation and reduction led to the 11'
      amino-ethyloxyundecyl E2. Using (1)H NMR analysis, it could be shown that the
      biotin moiety of the biotinylated 6alpha- and 7alpha-E2 derivatives has an axial
      position which results in a vertical orientation of the substituent toward the
      alpha-face of the planar tetracyclic backbone. Thus, a negligible alteration of
      the original structure of the upper beta-face offers the feasibility of applying
      the 6alpha- and 7alpha-derivatives as optimal tracers in competitive
      immunoassays.

PMID- 10898577
TI  - Tris(3-mercaptopropyl)-N-glycylaminomethane as a new linker to bridge antibody
      with metal particles for biological cell separations.
AB  - Conjugates of nickel beads with CD8 and anti-red blood cell KC16 antibody were
      prepared by using the aminotrithiolate "spider" ligand, tris(3-mercaptopropyl)-N
      glycylaminomethane, in its new function as a linker between the surface of nickel
      beads and antibody via activation of spider ligand attached to nickel beads with
      the common, heterobifunctional cross-linker, sulfosuccinimidyl 4-(N
      maleimidomethyl)cyclohexane-1-carboxylate (sulfo-SMCC). Raw nickel beads were
      cleaned by either mild sonication in a bath or by stronger probe sonication to
      remove surface nickel oxide layers, before attachment of the spider ligand.
      Scanning electron micrographs of the nickel beads before and after probe
      sonication showed a marked change from a corrugated to a smooth bead surface.
      Analyses of the supernatants of conjugation mixtures for antibody gave surface
      densities of 2.5-5.2 mg/m(2) for CD8 and 0.6-12 mg/m(2) for KC16 antibody runs.
      The antibody-spider-nickel bead conjugates were used in magnetic bead depletions
      of targeted CD8+ lymphocytes or red blood cells (rbcs) in whole blood of normal
      donors. For CD8 cell depletions, the undepleted controls and supernatants of
      depleted samples were analyzed for CD8/CD4 cell populations by flow cytometry
      with appropriate fluorescent antibody markers. Enumeration of red blood cells,
      white blood cells (wbcs), and platelets (plts) in undepleted controls and
      supernatants of depleted samples were carried out on appropriate hematology
      counters. Whole blood titer results with various lots of either CD8-spider-nickel
      or KC16-spider-nickel bead conjugates showed varying degrees of depletion ability
      as indicated by bead-to-cell ratios of 2-32 for CD8 beads and by rbc-to-bead
      ratios of 1.2-10 for KC16 beads. Moreover, varying degrees of specificity of CD8
      beads for CD8+ cells over CD4+ cells and of KC16 beads for rbcs over white blood
      cells and platelets were observed from the normalized nontargeted cell population
      figures in undepleted controls versus supernatants of depleted samples.

PMID- 10898578
TI  - Region-selective labeling of antibodies as determined by electrospray ionization
      mass spectrometry (ESI-MS).
AB  - The electrospray ionization-mass spectrometry (ESI-MS) analysis of three sets of
      monoclonal antibody-acridinium-9-carboxamide conjugates is described. The
      conjugates (nine total) were enzymatically digested using papain and the
      resulting fragments [Fc heavy chain, Fab, or F(ab')(2)] were analyzed using
      liquid chromatography/ESI-MS. The average number of labels per fragment were
      calculated using Sigma nx%, where n is the number of acridinium molecules
      covalently bound to the fragment and x% is the percent relative area of the
      corresponding peaks in the mass spectrum. When these values were normalized
      against the molecular weight of their respective region, antibody-dependent
      labeling patterns were observed. For antibodies T (anti-L-T(4)) and F (anti
      FITC), there was a preference for conjugation of the Fab region over the Fc
      region. For antibody B (anti-biotin), the trend was reversed.

PMID- 10898579
TI  - In vitro interleukin-3 binding to leukemia cells predicts cytotoxicity of a
      diphtheria toxin/IL-3 fusion protein.
AB  - Patients with acute myeloid leukemia frequently develop chemotherapy resistant
      blasts. To overcome multidrug resistance, a diphtheria toxin fusion protein
      (DTIL3) was engineered by fusing the catalytic and translocation domains of
      diphtheria toxin (DT) to human interleukin-3 (IL-3). However, when blasts were
      isolated from patients and tested for colony growth inhibition by DTIL3, only a
      third of the samples showed sensitivity to the fusion protein. Prior to clinical
      development, we need to be able to identify which patients are likely to respond
      to therapy with DTIL3. In this report, we compared the inhibition of thymidine
      incorporation in human leukemia cell lines by DTIL3 to the IL-3 receptor number
      and affinity. We found DTIL3 was cytotoxic to four of the eight cell lines tested
      with half-maximal inhibition of thymidine incorporation (IC(50)) from 1 to 50 pM.
      The IL-3 receptor density for these cell lines ranged from 0 to 2635 receptors
      per cell. The dissociation constant for an IL-3 high-affinity receptor agonist
      was 0.5 nM for cell lines with receptors. We found a correlation for the cell
      lines between the presence of high-affinity IL-3 receptors and sensitivity to
      DTIL3 (p = 0.03). These results suggest the variability in sensitivity of patient
      leukemic progenitors to DTIL3 may be due in part to the presence or absence of
      high-affinity IL-3 receptors.

PMID- 10898580
TI  - Biotin reagents for antibody pretargeting. 4. Selection of biotin conjugates for
      in vivo application based on their dissociation rate from avidin and
      streptavidin.
AB  - An investigation was conducted to determine the affect of structural variation of
      biotin conjugates on their dissociation rates from Av and SAv. This information
      was sought to help identify optimal biotin derivatives for in vivo applications.
      Fifteen biotin derivatives were conjugated with a cyanocobalamin (CN-Cbl)
      derivative for evaluation of their "relative" dissociation rates by size
      exclusion HPLC analysis. Two biotin-CN-Cbl conjugates, one containing unaltered
      biotin and the other containing iminobiotin, were prepared as reference compounds
      for comparison purposes. The first structural variations studied involved
      modification of the biotinamide bond with a N-methyl moiety (i.e., sarcosine
      conjugate), lengthening the valeric acid side chain by a methylene unit (i.e.,
      homobiotin), and replacing the biotinamide bond with thiourea bonds in two
      conjugates. The rate of dissociation of the biotin-CN-Cbl derivative from Av and
      SAv was significantly increased for biotin derivatives containing those
      structural features. Nine additional biotin conjugates were obtained by coupling
      amino acids or functional group protected amino acids to the biotin moiety. In
      the conjugates, the biotin moiety and biotinamide bond were not altered, but
      substituents of various sizes were introduced alpha to the biotinamide bond. The
      results obtained from HPLC analyses indicated that the rate of dissociation from
      Av or SAv was not affected by small substituents alpha to the biotinamide (e.g.,
      methyl, hydroxymethyl, and carboxylate groups), but was significantly increased
      when larger functional groups were present. On the basis of the results obtained,
      it appears that biotin conjugates which retain an unmodified biotin moiety and
      have a linker molecule conjugated to it that has a small functional group (e.g.,
      hydroxymethylene or carboxylate) alpha to the biotinamide bond are excellent
      candidates for in vivo applications. These structural features are obtained in
      the biotin amino acid conjugates: biotin-serine, biotin-aspartate, biotin-lysine,
      and biotin-cysteine. Importantly, these biotin derivatives can be readily
      conjugated with other molecules for specific in vivo applications. In our
      studies, these derivatives will be used in the design of new biotin conjugates to
      carry radionuclides for cancer therapy using the pretargeting approach.

PMID- 10898581
TI  - Evaluation of biotin-dye conjugates for use in an HPLC assay to assess relative
      binding of biotin derivatives with avidin and streptavidin.
AB  - In this investigation, studies were conducted to determine if size exclusion HPLC
      could be used to assess relative association rates (on-rates) and dissociation
      rates (off-rates) of biotin derivatives from avidin (Av) and streptavidin (SAv).
      For easy detection and quantification of biotin derivatives, molecules that can
      be detected by UV absorbance were conjugated to biotin. Concern that conjugation
      of the chromophoric moieties (dyes) might affect biotin binding with Av and SAv
      or might interact with the HPLC column led to evaluation of 10 biotin-dye
      conjugates. The dyes conjugated with biotin included dansyl, cyanocobalamin (CN
      Cbl), coumarin 343, Lissamine-rhodamine, fluorescein, Cascade Blue, Lucifer
      Yellow, Oregon Green, tetramethylrhodamine, and Alexa Fluor 594. The biotin-dye
      conjugates were initially evaluated to determine their peak characteristics on
      two different size exclusion HPLC columns. Measurement of the percent of biotin
      dye conjugate bound with Av in the presence of an equal quantity of biotin
      provided an association rate relative to biotin. All of the biotin-dyes tested
      had association rates within a factor of 3x (slower) that of biotin. The relative
      dissociation rate of biotin-dye conjugates was assessed by challenging the biotin
      conjugate bound to Av or SAv with a large excess of biotin. All of the initial
      biotin-dye conjugates tested bound Av and SAv tightly resulting in very slow
      dissociation rates. From the biotin-dye conjugates studied, biotin-CN-Cbl, 6b,
      was selected as the best conjugate for the HPLC assay. To test the HPLC assay, an
      iminobiotin-CN-Cbl conjugate, 13a, and a biotin-sarcosine-CN-Cbl conjugate, 13b,
      were synthesized. The fact that the iminobiotin does not bind with Av at
      physiological pH was easily detected in the size exclusion HPLC assay. The biotin
      sarcosine-CN-Cbl conjugate was expected to have a more rapid dissociation rate
      than the other biotin-dye conjugates. This was confirmed in that HPLC assay.
      Although 13b bound tightly with Av in the absence of added biotin, it was
      completely released within 1 h when challenged by an excess of biotin. A slower
      dissociation of 13b was noted with SAv. The results obtained indicate that CN-Cbl
      conjugates of biotin derivatives can be used to determine relative on-rates and
      off-rates of biotin derivatives with Av and SAv. The studies also demonstrated
      that the biotin-CN-Cbl conjugate, 6b, can be used as a reference compound to
      compare on-rates and off-rates of nonchromophoric biotin derivatives.

PMID- 10898582
TI  - Preparation of an imidazole-conjugated oligonucleotide.
AB  - Postsynthetic modification of an oligonucleotide with an imidazole functional
      group was achieved by formation of an amide bond between the functional group and
      a single 2'-amino-2'-deoxyuridine, d-aU, of the oligonucleotide. The succinimidyl
      ester of N-glutaryl-histamine was synthesized under anhydrous conditions and
      added to the oligonucleotide in an acetonitrile-containing buffer at pH 8.0.
      Formation of the conjugate was assayed by digestion with snake venom
      phosphodiesterase and bacterial alkaline phosphatase, followed by reversed-phase
      HPLC to resolve constituent nucleosides. The disappearance of a peak
      corresponding to d-aU and the appearance of a peak that coelutes with authentic
      2'-(N-glutaryl-N'-histaminyl)-2'-deoxyuridine confirmed the formation of the
      conjugate. Imidazole-conjugated oligonucleotides may have utility as antisense
      agents capable of hydrolyzing RNA.

PMID- 10898583
TI  - A reactive metabolite of furan, cis-2-butene-1,4-dial, is mutagenic in the Ames
      assay.
AB  - Furan is classified as a nongenotoxic hepatocarcinogen. It is thought to be
      activated to a toxic metabolite, cis-2-butene-1,4-dial, which is acutely toxic to
      liver cells. The resulting cytotoxicity is followed by compensatory cell
      proliferation, increasing the likelihood of tumor production. We examined the
      genotoxic activity of cis-2-butene-1,4-dial in several strains of Salmonella
      typhimurium commonly used in the Ames assay. This reactive compound tested
      positive in TA104, a strain that is sensitive to aldehydes. Mutagenic activity
      was concentration-dependent (1000 +/- 180 revertants/micromol). Incubation of cis
      2-butene-1,4-dial with glutathione prior to addition of bacteria inhibited both
      the acute toxic and genotoxic activity of this compound. No evidence of mutagenic
      activity was seen at nontoxic concentrations in TA97, TA98, TA100, and TA102. Our
      findings are consistent with the hypothesis that cis-2-butene-1,4-dial reacts
      with DNA to form mutagenic adducts. Our data suggest that cis-2-butene-1,4-dial
      may be an important genotoxic as well as toxic intermediate in furan-induced
      tumorigenesis.

PMID- 10898584
TI  - Isolation and identification of a new 2-phenylbenzotriazole-type mutagen (PBTA-3)
      in the Nikko river in Aichi, Japan.
AB  - We have previously determined the chemical structures of two 2
      phenylbenzotriazole mutagens (PBTA-1 and PBTA-2) in blue cotton-adsorbed material
      from the Nishitakase River in Kyoto, Japan. In the present study, further
      analysis of mutagenic substances in the Nikko River, which flows through Aichi
      Prefecture in Japan, allowed the isolation of a new mutagen. Material (2.2 g)
      adsorbed on blue cotton (3 kg) at a site below the sewage plant on the Nikko
      River was purified by various column chromatographies, and a mutagen (120 microg)
      accounting for 11% of the total mutagenicity was isolated. On the basis of data
      from UV, mass, and (1)H NMR spectra of the mutagen, the compound was deduced to
      be a PBTA-1 analogue. As with PBTA-1, the mutagen was able to be synthesized from
      the azo dye 2-[(2-bromo-4, 6-dinitrophenyl)azo]-4-methoxy-5-[(2
      hydroxyethyl)amino]acetanilide by reduction and chlorination. Since all spectra
      of the mutagen isolated from the river water were the same as those of the
      synthesized form, the structure was concluded to be 2-[2-(acetylamino)-4-[(2
      hydroxyethyl)amino]-5-methoxyphenyl]-5-amino -7-bromo-4-chloro-2H-benzotriazole
      (PBTA-3). PBTA-3 is a potent mutagen, inducing 81 000 and 3 000 000 revertants
      per microgram of Salmonella typhimurium TA 98 and YG1024 respectively, in the
      presence of an S9 mix. In addition to its detection in the water of the Nikko
      River, PBTA-3 was detected in water samples from three other rivers flowing
      through regions where dyeing industries have been developed. Like PBTA-1 and PBTA
      2, PBTA-3 might have also been produced from azo dyes during industrial processes
      in dyeing factories and/or through treatment at sewage plants.

PMID- 10898585
TI  - DNA damage induced in cells by gamma and UVA radiation as measured by HPLC/GC-MS
      and HPLC-EC and Comet assay.
AB  - The aim of the work was to measure DNA damage induced within tumoral human
      monocytes by gamma rays, UVA radiation, and exogenous photosensitizers. The
      accurate HPLC-EC assay was used to determine the level of 8-oxodGuo. The
      formation of FapyGua and FapyAde was monitored by HPLC/GC-MS analyses after
      formic acid hydrolysis at room temperature. For this purpose, cells were exposed
      to relatively high doses of gamma rays and UVA radiation. The extent of formation
      of FapyGua in the DNA of cells exposed to gamma rays was estimated to be more
      than 2-fold higher than that of 8-oxodGuo, i.e., about 0. 027 lesion per 10(6)
      bases per Gy. The yield of FapyAde was estimated to be 1 order of magnitude
      lower. The latter results were used to calibrate the alkaline comet assay
      associated with DNA N-glycosylases. The latter approach allowed the determination
      of the background level (0.11-0.16 Fpg-sensitive site/10(6) bases) and the yields
      of strand breaks and DNA base damage upon low irradiation doses. Insights into
      the mechanism of radiation-induced DNA damage were gained from these
      measurements. A major involvement of (1)O(2) with respect to hydroxyl radicals
      and type I photosensitization was thus observed within cells exposed to UVA
      radiation.

PMID- 10898586
TI  - The putative benzene metabolite 2,3, 5-tris(glutathion-S-yl)hydroquinone depletes
      glutathione, stimulates sphingomyelin turnover, and induces apoptosis in HL-60
      cells.
AB  - In this study, we show that 2,3,5-tris(glutathion-S-yl)hydroquinone (TGHQ), a
      putative metabolite of benzene, induces apoptosis in human promyelocytic leukemia
      (HL-60) cells. Prior to the onset of apoptosis, TGHQ depletes intracellular
      glutathione (GSH) in a reactive oxygen species (ROS)-independent manner. Neutral,
      Mg(2+)-dependent sphingomyelinases, which are normally inhibited by GSH, are
      subsequently activated, as evidenced by increases in intracellular ceramide and
      depletion of sphingomyelin. As ceramide levels rise, effector caspase (DEVDase)
      activity steadily increases. Interestingly, while catalase has no effect on TGHQ
      mediated depletion of GSH, this hydrogen peroxide (H(2)O(2)) scavenger does
      inhibit DEVDase activity and apoptosis, provided the enzyme is added to HL-60
      cells before an increase in ceramide can be observed. Since ceramide analogues
      inhibit the mitochondrial respiratory chain, these data imply that ceramide
      mediated generation of H(2)O(2) is necessary for the activation of effector
      caspases-3 and/or -7, and apoptosis. In summary, these studies indicate that
      TGHQ, and perhaps many quinol-based toxicants and chemotherapeutics, may induce
      apoptosis in hematopoietic cells by depleting GSH and inducing the proapoptotic
      ceramide-signaling pathway.

PMID- 10898587
TI  - HNE-derived 2-pentylpyrroles are generated during oxidation of LDL, are more
      prevalent in blood plasma from patients with renal disease or atherosclerosis,
      and are present in atherosclerotic plaques.
AB  - Free radical oxidation of human plasma low-density lipoprotein (LDL) produces 2
      pentylpyrrole epitopes that are generated by reaction of 4-hydroxy-2-nonenal
      (HNE), a product of lipid oxidation, with protein lysyl residues. The HNE-derived
      2-pentylpyrrole ("HNE-pyrrole") epitopes were detected with an enzyme-linked
      immunosorbent assay (ELISA) using antibodies (ON-KLH) raised against protein
      bound 2-pentylpyrrole obtained by the reaction of 2-oxononanal (ON) with keyhole
      limpet hemocyanin (KLH). HNE-pyrrole epitopes in human plasma are not associated
      primarily with LDL protein, apolipoprotein (apo) B, since only 15% of the total
      HNE-pyrrole immunoreactivity is removed by immunoprecipitation of apo B. The
      levels of ON-KLH immunoreactivity detected in human plasma were found to be
      significantly elevated in renal failure and atherosclerosis patients when
      compared to those in healthy volunteers. HNE-pyrrole immunoreactivity was also
      detected in atherosclerotic plaques. The highest levels were associated with
      extracellular connective tissue. Levels of ON-KLH immunoreactivity in human
      plasma far exceed levels of free HNE, presumably because of the rapid clearance
      of free relative to protein-bound HNE. Therefore, HNE-pyrrole epitopes provide a
      more indelible marker of oxidative injury than levels of free HNE.

PMID- 10898588
TI  - Characterization of 2'-deoxyadenosine adducts derived from 4-oxo-2-nonenal, a
      novel product of lipid peroxidation.
AB  - Analysis of the reaction between 2'-deoxyadenosine and 4-oxo-2-nonenal by liquid
      chromatography/mass spectrometry revealed the presence of three major products
      (adducts A(1), A(2), and B). Adducts A(1) and A(2) were isomeric; they
      interconverted at room temperature, and they each readily dehydrated to form
      adduct B. The mass spectral characteristics of adduct B obtained by collision
      induced dissociation coupled with multiple tandem mass spectrometry were
      consistent with those expected for a substituted etheno adduct. The structure of
      adduct B was shown by NMR spectroscopy to be consistent with the substituted
      etheno-2'-deoxyadenosine adduct 1' '-[3-(2'-deoxy-beta-D-erythropentafuranosyl)
      3H-imidazo[2, 1-i]purin-7-yl]heptane-2' '-one. Unequivocal proof of structure
      came from the reaction of adducts A(1) and A(2) (precursors of adduct B) with
      sodium borohydride. Adducts A(1) and A(2) each formed the same reduction product,
      which contained eight additional hydrogen atoms. The mass spectral
      characteristics of this reduction product established that the exocyclic amino
      group (N(6)) of 2'-deoxyadenosine was attached to C-1 of the 4-oxo-2-nonenal. The
      reaction of 4-oxo-2-nonenal with calf thymus DNA was also shown to result in the
      formation of substituted ethano adducts A(1) and A(2) and substituted etheno
      adduct B. Adduct B was formed in amounts almost 2 orders of magnitude greater
      than those of adducts A(1) and A(2). This was in keeping with the observed
      stability of the adducts. The study presented here has provided additional
      evidence which shows that 4-oxo-2-nonenal reacts efficiently with DNA to form
      substituted etheno adducts.

PMID- 10898589
TI  - Repair and coding properties of 5-hydroxy-5-methylhydantoin nucleosides inserted
      into DNA oligomers.
AB  - 1-(2-Deoxy-beta-D-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin (5-OH-5-Me
      dHyd) (3) has been shown to be a major oxidation product of thymidine formed upon
      exposure of DNA to (*)OH-radical and excited photosensitizers. To investigate the
      biological and structural significance of the 5-OH-5-Me-dHyd residue to DNA, the
      latter modified 2'-deoxyribonucleoside was chemically prepared and then site
      specifically incorporated into oligodeoxyribonucleotides. This was efficiently
      achieved using the phosphoramidite approach that involved mild deprotection
      conditions. The purity and the integrity of the modified synthetic DNA fragments
      were checked using different complementary techniques such as HPLC and
      polyacrylamide gel electrophoresis, together with electrospray ionization and
      MALDI-TOF mass spectrometry. The piperidine test applied to 5-OH-5-Me-dHyd
      containing oligonucleotides showed a weak instability of hydantoin nucleoside
      inserted into the oligonucleotide chain. Several enzymatic experiments aimed at
      determining the biochemical features of such a DNA lesion were carried out. Thus,
      processing of 5-OH-5-Me-dHyd by nuclease P(1), snake venom phosphodiesterase, and
      calf spleen phosphodiesterase was investigated. The specificity and the mechanism
      of excision of the lesion by several bacterial and yeast DNA N-glycosylases,
      namely, endonuclease III (endo III), endonuclease VIII (endo VIII),
      formamidopyrimidine DNA N-glycosylase (Fpg), Ntg1 protein (Ntg1), Ntg2 protein
      (Ntg2), and Ogg1 protein (yOgg1), were also determined. These repair studies
      clearly showed that all these enzymes, with the exception of the yOgg1 protein,
      are able to recognize and remove 5-hydroxy-5-methylhydantoin from the double
      stranded DNA fragment. Finally, a 22-mer DNA oligomer bearing a 5-OH-5-Me-dHyd
      residue was used as a template to study the in vitro nucleotide incorporation
      opposite the damage by the Klenow fragment of Escherichia coli polymerase I, Taq
      DNA polymerase, and DNA polymerase beta. Thus, it may be concluded that the
      oxidized thymine residue is a strongly blocking lesion for the three studied DNA
      polymerases.

PMID- 10898590
TI  - UVA-Induced DNA single-strand cleavage by 1-hydroxypyrene and formation of
      covalent adducts between DNA and 1-hydroxypyrene.
AB  - 1-Hydroxypyrene (HOP), a metabolite found in the urine of humans and laboratory
      animals exposed to polycyclic aromatic hydrocarbons (PAHs), is known to be both
      acutely toxic and genotoxic. It has been widely used as a biomarker for studying
      PAH exposure. In this research, we have found that, upon UVA irradiation, HOP
      causes DNA single-strand cleavages and forms HOP-DNA covalent adducts. The UVA
      induced cleavage of supercoiled plasmid PhiX174 DNA is dependent upon both HOP
      concentration and UVA dosage. A longer irradiation time or higher HOP
      concentration induces more DNA cleavage. Results of the photocleavage experiments
      carried out in the presence of reactive oxygen species scavengers, histidine,
      sodium azide, mannitol, SOD, and desferal indicate that both the superoxide free
      radical and singlet oxygen are likely involved in causing DNA single-strand
      cleavage. The photocleavage is inhibited by the presence of an excited singlet
      state quencher, KI, indicating that it is an excited-state reaction. Along with
      light-induced DNA cleavage, HOP also forms DNA covalent adducts while being
      degraded upon light irradiation. Light-induced degradation of 20 microM HOP
      follows first-order reaction kinetics in a 10% methanolic buffer (10 mM
      phosphate) solution in the absence or presence of 40 microM calf thymus DNA, with
      degradation half-lives of 20 or 15 min, respectively. The shorter degradation
      half-life in the presence of DNA is due to the formation of the HOP-DNA covalent
      adduct. The formation of the HOP-DNA covalent adduct is evidenced by comparing
      the UV-vis absorption and fluorescence emission spectra of the pure HOP with
      those of the HOP-DNA adduct. The covalent HOP-DNA adduct produced due to
      irradiation was purified by either extensive dialysis (3 x 500 mL buffer
      solutions), phenol and chloroform extraction followed by ethanol precipitation,
      or chloroform extraction alone. The isolated HOP-DNA adduct has an absorption
      peak at 353 nm, which is 8 nm red-shifted compared to that of free HOP. The
      fluorescence emission for HOP-DNA is at least 70 times weaker than that for free
      HOP in solution. In summary, the findings with HOP reveal that, in addition to
      metabolic activation that eventually leads to the formation of alkylated DNA
      adducts or other forms of DNA damage, HOP may be activated by light to produce
      DNA single-strand cleavage and covalent DNA adducts. These DNA lesions can be
      sources of toxicity.

PMID- 10898591
TI  - Lead interaction with human protamine (HP2) as a mechanism of male reproductive
      toxicity.
AB  - During spermatogenesis, histones are replaced by protamines, which condense and
      protect sperm DNA. In humans, zinc contributes to sperm chromatin stability and
      binds to protamine P2 (HP2). Chemical interactions with nuclear protamines, which
      prevent normal sperm chromatin condensation, may induce changes in the sperm
      genome and thus affect fertility and offspring development. Since lead has a high
      affinity for zinc-containing proteins, we investigated lead interactions with HP2
      as a novel mechanism of its toxicity to sperm. UV/vis and CD spectroscopy results
      indicated that HP2 binds Pb(2+) at two different sites, causing a conformational
      change in the protein. They also provided evidence that thiol groups are
      primarily involved in Zn(2+) and Pb(2+) binding to HP2 and that HP2 may have
      additional binding sites for Pb(2+) not related to Zn(2+). HP2 affinities for
      Pb(2+) and Zn(2+) were very similar, suggesting that Pb(2+) can compete with or
      replace Zn(2+) in HP2 in vivo. This interaction of lead with HP2 resulted in a
      dose-dependent decrease in the extent of HP2-DNA binding, although lead
      interaction with DNA also contributed to this effect. Therefore, the ability of
      lead to decrease the level of HP2-DNA interaction may result in alterations to
      sperm chromatin condensation, and thus in reduced fertility.

PMID- 10898592
TI  - trans,trans-2,4-decadienal-induced 1,N(2)-etheno-2'-deoxyguanosine adduct
      formation.
AB  - A number of ring-extended DNA adducts resulting from the reaction of alpha,beta
      unsaturated aldehydes, or their epoxides, with DNA bases have been characterized
      in recent years. These adducts may lead to miscoding during DNA replication,
      resulting, if not repaired, in mutations that can contribute to cancer
      development. trans,trans-2, 4-Decadienal (DDE) is one of the highly cytotoxic
      aldehydes endogenously formed from lipid peroxidation. To evaluate its DNA
      damaging potential, we have investigated the reaction of DDE with 2'
      deoxyguanosine (dGuo) in the presence of peroxides. Three stable adducts were
      isolated by reverse-phase HPLC. Adduct A1, 3-(2-deoxy-beta-D-erythro
      pentafuranosyl)-5,9-dihydro-9H-imidazo[2 , 1-i]purin-9-hydroxy, is a tautomer of
      1, N(2)-etheno-2'-deoxyguanosine, a well-known reaction product of epoxy
      aldehydes with dGuo. Two new diasteroisomeric products, A2-1 and A2-2, 1-?[3-(2'
      deoxy-beta-D-erythro-pentafuranosyl)-5, 9-dihydro-9H-imidazo[2,1-i]purin-9
      hydroxy]-7-yl?-2-one-3-octanol, were isolated and characterized on the basis of
      their spectroscopic features as 1,N(2)-etheno adducts possessing a carbon side
      chain with a carbonyl and a hydroxyl group. The proposed reaction mechanism for
      the formation of adducts A2 involves DDE double epoxidation and hydrolysis of the
      C4 epoxy group prior to nucleophilic addition of the exocyclic amino group of
      dGuo to C1 of the aldehyde, followed by cyclization via nucleophilic attack on
      the C2 epoxy group by N-1 and elimination of H(2)O. After treatment of calf
      thymus DNA with DDE, formation of adducts A1 and A2 was detected by the LC/ESI/MS
      MS technique. These results can contribute to a better understanding of the
      chemical structures of adducts resulting from the reaction of aldehydes with
      nucleic acid bases, a necessary step in assessing the genotoxic risks associated
      with this class of compounds.

PMID- 10898593
TI  - Bioactivation mechanisms of haloalkene cysteine S-conjugates modeled by gas
      phase, ion-molecule reactions.
AB  - Glutathione conjugate formation plays important roles in the detoxification and
      bioactivation of xenobiotics. A range of nephrotoxic haloalkenes undergo
      bioactivation that involves glutathione and cysteine S-conjugate formation. The
      cysteine S-conjugates thus formed may undergo cysteine conjugate beta-lyase
      catalyzed biotransformation to form cytotoxic thiolates or thiiranes. In the
      studies presented here, cysteine conjugate beta-lyase-catalyzed
      biotransformations were modeled by anion-induced elimination reactions of S-(2
      bromo-1,1, 2-trifluoroethyl)-N-acetyl-L-cysteine methyl ester, S-(2-chloro-1,1, 2
      trifluoroethyl)-N-acetyl-L-cysteine methyl ester, and S-(2-fluoro-1,1,2
      trifluoroethyl)-N-acetyl-L-cysteine methyl ester in the gas phase. Examination of
      these processes in the gas phase allowed direct observation of the formation of
      cysteine S-conjugate-derived thiolates and thiiranes, whose formation is inferred
      from condensed-phase results. The cysteine S-conjugates of these haloethenes
      exhibit distinctive patterns of mutagenicity that are thought to be correlated
      with the nature of the products formed by their cysteine conjugate beta-lyase
      catalyzed biotransformation. In particular, S-(2-bromo-1,1,2-trifluoroethyl)-L
      cysteine is mutagenic, whereas the chloro and fluoro analogues are not. It has
      been proposed that the mutagenicity of S-(2-bromo-1,1, 2-trifluoroethyl)-L
      cysteine is correlated with the greater propensity of the bromine-containing
      cysteine S-conjugate to form a thiirane compared with those of the chlorine- or
      fluorine-containing conjugates. The ease of thiirane formation is consistent with
      the gas-phase results presented here, which show that the bromine-containing
      conjugate has a greater propensity to form a thiirane on anionic base-induced
      elimination than the chloro- or fluoro-substituted analogues. The blocked
      cysteine S-conjugates were deprotonated by gas-phase ion-molecule reactions with
      hydroxide, methoxide, and ethoxide ions and then allowed to decompose. The
      mechanisms for these decompositions are discussed as well as the insights into
      the bioactivation of these cysteine S-conjugates provided by the further
      decompositions of thiolate intermediates.

PMID- 10898595
TI  - Studies of the mechanisms of adduction of 2'-deoxyadenosine with styrene oxide
      and polycyclic aromatic hydrocarbon dihydrodiol epoxides.
AB  - The mechanism of adduction of 2'-deoxyadenosine by styrene oxide and polycyclic
      aromatic hydrocarbon dihydrodiol epoxides has been explored using (15)N(6)
      labeled adenine nucleosides. The extent of reaction at N1 versus N(6) was
      evaluated by (1)H NMR of the N(6) adducts after allowing Dimroth rearrangement to
      occur. Products arising from attack at N1 followed by Dimroth rearrangement
      exhibited a small two-bond (1)H-(15)N coupling constant (N1-H2 J approximately 13
      Hz); products from direct attack exhibited a much larger one-bond (1)H-(15)N
      coupling constant (J approximately 90 Hz). In the case of styrene oxide, all of
      the N(6) beta adduct arose by initial attack at N1, whereas the majority (70-80%)
      of the N(6) alpha adducts came from direct attack. The styrene oxide reaction was
      also studied with a self-complementary oligodeoxynucleotide (24-mer) containing
      nine (15)N(6)-labeled adenine residues. NMR examination of the N(6) alpha- and
      beta-styrene oxide adducts isolated after enzymatic degradation of the 24-mer
      gave very similar results, indicating that N1 attack can occur readily even with
      a duplexed oligonucleotide. With the PAH dihydrodiol epoxides, only naphthalene
      dihydrodiol epoxide exhibited significant initial reaction at N1 (50%). No
      detectable rearranged product was seen in reactions with benzo[a]pyrene
      dihydrodiol epoxide or non-bay or bay region benz[a]anthracene dihydrodiol
      epoxide; interestingly, a small amount of N1 attack (5-7%) was seen in the case
      of benzo[c]phenanthrene dihydrodiol epoxide. It appears that initial attack at N1
      is only a significant reaction pathway for epoxides attached to a single aromatic
      ring.

PMID- 10898594
TI  - Ni(II) specifically cleaves the C-terminal tail of the major variant of histone
      H2A and forms an oxidative damage-mediating complex with the cleaved-off
      octapeptide.
AB  - The acetyl-TESHHK-amide peptide, modeling a part of the C-terminal "tail" of
      histone H2A, was found previously by us to undergo at pH 7. 4 a Ni(II)-assisted
      hydrolysis of the E-S peptide bond with formation of a stronger Ni(II) complex
      with the SHHK-amide product [Bal, W., et al. (1998) Chem. Res. Toxicol. 11, 1014
      1023]. To further characterize the hydrolysis and test the resulting Ni(II)
      complex for redox activity, bovine histone H2A and three peptides were
      investigated: acetyl-LLGKVTIAQGGVLPNIQAVLLPKKTESHHKAKGK (H2A(34)), modeling the
      entire "C-tail" of H2A; SHHKAKGK (H2A(8)), modeling the cutoff product of
      hydrolysis; and acetyl-KTESHKAKGK (H2A(10)), modeling a putative Ni(II) binding
      site in a minor variant H2A.4 of human histone H2A. The Ni(II)-assisted
      hydrolysis of H2A and H2A(34) was found to proceed approximately 7-fold faster
      than that of the Ni(II)-acetyl-TESHHK-amide complex under comparable conditions.
      In both cases, the Ni(II) complex with H2A(8) was the smaller product of the
      hydrolysis, indicating a high site specificity of the reaction. Of three other
      metals tested with H2A(34), only Cu(II) cleaved the E-S bond, although much less
      efficiently than Ni(II); Co(II) and Zn(II) had no effect whatsoever. The H2A(10)
      peptide appeared to be fully resistant to hydrolytic cleavage and did not exhibit
      any redox activity versus H(2)O(2) in the presence of Ni(II) at pH 7.4. Likewise,
      redox-inactive was the Ni(II)-H2A(34) complex. In contrast, the Ni(II)-H2A(8)
      complex promoted oxidative damage of pUC19 DNA by H(2)O(2), evidenced by a
      significant increase in the number of single strand breaks and nucleobase
      modifications typical for a hydroxyl radical-like species attack on DNA.
      Interestingly, instead of 8-oxopurines, the corresponding formamidopyrimidines
      were the major products of the damage. The difference in redox activity between
      the Ni(II)-H2A(34) and Ni(II)-H2A(8) complexes is most likely associated with
      their different geometries: octahedral and square planar, respectively.
      Incubation of the Ni(II)-H2A(8) complex with H(2)O(2) also resulted in
      degradation of the peptide ligand, especially at its Ser and His residues. Thus,
      binding of Ni(II) to the ESHHK motif of the histone H2A C-tail is damaging to the
      histone C-terminal tail and to histone-associated DNA. The results support a dual
      mechanism of Ni(II)-induced carcinogenesis, including both genotoxic and
      epigenetic effects.

PMID- 10898596
TI  - Reactions of Genistein with alkylperoxyl radicals.
AB  - Antioxidant actions of the soy isoflavone genistein are believed to contribute to
      its overall chemopreventive activity. However, the mechanisms of its antioxidant
      reactions remain unknown. The objective of this study was to characterize the
      reaction products of genistein (5,7,4'-trihydroxyisoflavone) with peroxyl
      radicals generated by thermolysis of 2,2'-azobis(2,4-dimethylvaleronitrile)
      (AMVN). Genistein oxidations with AMVN-derived peroxyl radicals yielded orobol
      (5,7,3',4'-tetrahydroxyisoflavone), a hydroxylated derivative of genistein, and
      several stable adducts of 4'-oxogenistein with AMVN-derived radicals. Some of
      these adducts include novel structures resulting from secondary oxidations of the
      AMVN-derived moiety. For all the observed oxidation products, the modifications
      occurred on the B-ring of the molecule. Genistein oxidation product structures
      provide potentially useful markers of genistein antioxidant chemistry.

PMID- 10898597
TI  - Phosphobutyrylcholinesterase: phosphorylation of the esteratic site of
      butyrylcholinesterase by ethephon [(2-chloroethyl)phosphonic acid] dianion.
AB  - Ethephon [(2-chloroethyl)phosphonic acid] has two seemingly unrelated types of
      biological activity. It is a major agrochemical absorbed by crops, slowly
      releasing ethylene as a plant growth regulator. Ethephon also inhibits the
      activity of plasma butyrylcholinesterase (BuChE) in humans, dogs, rats, and mice.
      This is totally unexpected for an ionized phosphonic acid (mostly the dianion at
      physiological pH), in contrast to the classical inhibitors (nonionized triester
      phosphates) which phosphorylate serine at the active site. This study tests the
      hypothesis that ethephon (as the dianion) also acts as a phosphorylating agent in
      inhibiting BuChE activity. The sensitivity of plasma BuChE to ethephon (90 min
      preincubation at 25 degrees C) is greatest for humans, dogs, and mice (IC(50) = 6
      23 microM), intermediate for chickens, rabbits, rats, and guinea pigs (IC(50) =
      26-53 microM), and lowest for pigs and horses (IC(50) = 92-172 microM). The
      IC(50) decreases linearly with time on a log-log scale to values of 0.15-0. 3
      microM for human, dog, and horse BuChE at 24 h. The inhibition rate is generally
      related to ethephon concentration, consistent with a bimolecular reaction, e.g.,
      phosphorylation. The extent of inhibition of the esteratic activity of BuChE by
      ethephon is directly proportional to the extent of inhibition of
      [(3)H]diisopropyl phosphorofluoridate ([(3)H]DFP) postlabeling which is not
      reversible on removing the ethephon, either directly or after further incubation
      for 24 h at 25 degrees C. These observations strongly suggest that ethephon, as
      DFP, phosphorylates human plasma BuChE at Ser-198 of the esteratic site, or more
      generally, the formation of a phosphobutyrylcholinesterase. With human plasma
      BuChE, (2-bromoethyl)- and (2-iodoethyl)phosphonic acids have lower affinities
      for the site than ethephon but higher phosphorylation rate constants, consistent
      with their relative hydrolysis rates at pH 7.4 (phosphorylation of water). (2
      Chlorohexyl)phosphonic acid is a poor inhibitor, perhaps being too reactive with
      water. Thus, potency differences for ethephon and its analogues with BuChE of
      various species depend on both the affinities and phosphorylation rates, i.e.,
      the binding and reactivity of the (2-haloalkyl)phosphonic acid dianion in the
      esteratic site.

PMID- 10898598
TI  - Phosphoacetylcholinesterase: toxicity of phosphorus oxychloride to mammals and
      insects that can be attributed to selective phosphorylation of
      acetylcholinesterase by phosphorodichloridic acid.
AB  - Phosphorus oxychloride (POCl(3)) is an intermediate in the synthesis of many
      organophosphorus insecticides and chemical warfare nerve gases that are toxic to
      insects and mammals by inhibition of acetylcholinesterase (AChE) activity. It was
      therefore surprising to observe that POCl(3), which is hydrolytically unstable,
      also itself gives poisoning signs in ip-treated mice and fumigant-exposed
      houseflies similar to those produced by the organophosphorus ester insecticides
      and chemical warfare agents. In mice, POCl(3) inhibits serum
      butyrylcholinesterase (BuChE) at a sublethal dose and muscle but not brain AChE
      at a lethal dose. In houseflies, POCl(3)-induced brain AChE inhibition is
      correlated with poisoning and the probable cause thereof. POCl(3) in vitro is
      selective for AChE (IC(50) = 12-36 microM) compared with several other serine
      hydrolases (BuChE, carboxylesterase, elastase, alpha-chymotrypsin, and thrombin)
      (IC(50) = 88-2000 microM). With electric eel AChE, methylcarbamoylation of the
      active site with eserine reversibly protects against subsequent irreversible
      inhibition by POCl(3). Most importantly, POCl(3)-induced electric eel AChE
      inhibition prevents postlabeling with [(3)H]diisopropyl phosphorofluoridate;
      i.e., both compounds phosphorylate at Ser-200 in the catalytic triad. Pyridine-2
      aldoxime methiodide does not reactivate POCl(3)-inhibited AChE, consistent with
      an anionic phosphoserine residue at the esteratic site. The actual
      phosphorylating agent is formed within seconds from POCl(3) in water, has a half
      life of approximately 2 min, and is identified as phosphorodichloridic acid
      [HOP(O)Cl(2)] by (31)P NMR and derivatization with dimethylamine to
      HOP(O)(NMe(2))(2). POCl(3) on reaction with water and HOP(O)Cl(2) have the same
      potency for inhibition of AChE from either electric eel or housefly head as well
      as the same toxicity for mice. In summary, the acute toxicity of POCl(3) is
      attributable to hydrolytic activation to HOP(O)Cl(2) that phosphorylates AChE at
      the active site to form enzymatically inactive [O-phosphoserine]AChE.

PMID- 10898599
TI  - Peroxynitrite-induced secondary oxidative lesions at guanine nucleobases:
      chemical stability and recognition by the Fpg DNA repair enzyme.
AB  - Synthetic oligodeoxynucleotides containing secondary oxidative lesions at guanine
      nucleobases have been prepared by the site-specific oxidation by ONOO(-) of
      oligomers containing 8-oxoguanine (8-oxo-G). The oligomers have been tested for
      their stability to the standard hot piperidine treatment that is commonly used to
      uncover oxidized DNA lesions. While DNA containing oxaluric acid and oxazolone
      was cleaved at the site of modification under hot piperidine conditions, the
      corresponding cyanuric acid and 8-oxo-G lesions were resistant to piperidine. The
      recognition of the oxidative lesions by formamidopyrimidine glycosylase (Fpg
      enzyme) was examined in double-stranded versions of the synthetic
      oligodeoxynucleotides. Fpg efficiently excised 8-oxo-G and oxaluric acid and to
      some extent oxazolone, but not cyanuric acid. These data suggest that some DNA
      lesions formed via ONOO(-) exposures (cyanuric acid) are not repaired by Fpg and
      are not uncovered by assays based on piperidine cleavage at the site of lesion.
      Our results indicate that cryptic secondary and tertiary oxidation products
      arising from 8-oxo-G may contribute to the overall mutational spectra arising
      from oxidative stress.

PMID- 10898600
TI  - Radicals derived from histone hydroperoxides damage nucleobases in RNA and DNA.
AB  - Exposure of individual histone proteins (H1, H2A, H2B, H3, or H4) and histone
      octamers (consisting of two molecules each of H2A, H2B, H3, and H4) to hydroxyl
      radicals, generated by gamma-irradiation, in the presence of O(2) generates
      protein-bound hydroperoxides in a dose-dependent fashion; this is in accord with
      previous studies with other proteins. These histone hydroperoxides are stable in
      the absence of exogenous catalysts (e.g., heat, light, and transition metal
      ions), but in the presence of these agents decompose rapidly to give a variety of
      radicals which have been identified by EPR spin trapping. Histone hydroperoxide
      derived radicals generated on decomposition of the hydroperoxides with Cu(+)
      react with both pyrimidine and purine nucleobases. Thus, with uridine the histone
      hydroperoxide-derived radicals undergo addition across the C(5)-C(6) double bond
      of the pyrimidine ring to give cross-linked adduct species which have been
      identified by EPR spectroscopy. HPLC analysis of the products generated on
      reaction of histone hydroperoxide-derived radicals with 2'-deoxyguanosine, or
      intact calf thymus DNA, has shown that significant levels of the mutagenic
      oxidized DNA base 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) are formed, with
      the yield dependent on the individual histone protein, the presence of
      hydroperoxide functions, and the concentration of metal ion. These studies
      demonstrate that initial oxidative damage to individual histone proteins or
      histone octamers can result in the transfer of oxidative damage to associated DNA
      via the formation and subsequent decomposition of protein hydroperoxides to
      reactive radicals, and provide a novel route for the formation of mutagenic
      lesions in DNA.

PMID- 10898601
TI  - Thermal and physicochemical properties of rice grain, flour and starch.
AB  - Three types of rices, namely, Thailand rice (Indica), Nipponbare (Japonica), and
      Himenomochi (Japonica waxy), in grain, flour, and starch forms have been studied
      for their thermal and physicochemical properties. In grain form, Indica was
      slender and Japonica rices were bold and thick. Indica had the highest protein
      and amylose equivalent. Protein contents in isolated starches varied from 0.2 to
      0.9%. Cooked Indica grain was hardest and waxy rice was softest; stickiness was
      highest in Japonica rice. Glass transition temperature (T(g)) was highest in
      Indica rice flour (approximately 222 degrees C) and almost the same in Japonica
      rice flours. Melting point was highest for Japonica (approximately 264 degrees C)
      and almost the same for Japonica waxy and Indica rice flours. T(g) values of
      starches were almost the same in Indica and Japonica waxy (approximately 237
      degrees C); defatting caused reduction in this property in all of the starches.
      Highest melting point was shown by Indica starch (approximately 276 degrees C)
      and was almost the same for the other two starches. Protein and fats play a
      critical role in glass transition and melting points of rice flours and their
      respective starches. Viscosities of the cooked pastes of flour and starch during
      cooking in an RVA instrument and their gel and other properties have been
      discussed.

PMID- 10898602
TI  - Identification of fish species after cooking by SDS-PAGE and urea IEF: a
      collaborative study.
AB  - A collaborative study, to validate the use of SDS-PAGE and urea IEF, for the
      identification of fish species after cooking has been performed by nine
      laboratories. By following optimized standard operation procedures, 10
      commercially important species (Atlantic salmon, sea trout, rainbow trout,
      turbot, Alaska pollock, pollack, pink salmon, Arctic char, chum salmon, and New
      Zealand hake) had to be identified by comparison with 22 reference samples. Some
      differences in the recoveries of proteins from cooked fish flesh were noted
      between the urea and the SDS extraction procedures used. Generally, the urea
      extraction procedure appears to be less efficient than the SDS extraction for
      protein solubilization. Except for some species belonging to the Salmonidae
      family (Salmo, Oncorhynchus), both of the analytical techniques tested (urea IEF,
      SDS-PAGE) enabled identification of the species of the samples to be established.
      With urea IEF, two laboratories could not differentiate Salmo salar from Salmo
      trutta. The same difficulties were noted for differentiation between Oncorhynchus
      gorbuscha and Oncorhynchus keta samples. With SDS-PAGE, three laboratories had
      some difficulties in identifying the S. trutta samples. However, in the contrast
      with the previous technique, SDS-PAGE allows the characterization of most of the
      Oncorhynchus species tested. Only Oncorhynchus mykiss was not clearly recognized
      by one laboratory. Therefore, SDS-PAGE (Excel gel homogeneous 15%) appears to be
      better for the identification, after cooking, of fish such as the tuna and salmon
      species which are characterized by neutral and basic protein bands, and urea IEF
      (CleanGel) is better for the gadoid species, which are characterized by acid
      protein bands (parvalbumins). Nevertheless, in contentious cases it is preferable
      to use both analytical methods.

PMID- 10898603
TI  - Flavonoid glycosides of Barbarea vulgaris L. (Brassicaceae).
AB  - Seven flavonoid derivatives were for the first time isolated from aerial parts of
      an alimentary and medicinal plant of the Brassicaceae family, Barbarea vulgaris
      L. The products were characterized on the basis of spectroscopic NMR ((1)H,
      (13)C, COSY, HMQC, HMBC) and FAB-MS data. The occurrence of flavonoids in this
      plant is interesting for their important nutritional properties and for
      chemotaxonomical pourposes.

PMID- 10898604
TI  - Occurrence of flavonols in tomatoes and tomato-based products.
AB  - The flavonol contents of 20 varieties of tomato fruit were investigated in
      relation to variety, size, season, and country of origin. Ten commonly consumed
      tomato-based food products were also assessed. Free and conjugated flavonols were
      identified and quantified using reversed-phase HPLC. Ninety-eight percent of
      flavonols detected in tomatoes were found to occur in the skin. Tomatoes
      contained, primarily as conjugates, quercetin and kaempferol. The main quercetin
      conjugate was identified as rutin (quercetin 3-rhamnosylglucoside) by LC-MS. The
      total flavonol content of the different varieties of tomato that were analyzed
      varied from 1.3 to 22.2 microgram/g of fresh weight (fw). Smaller cherry tomato
      fruits originating from warm sunny climates, such as Spain and Israel, were found
      to contain the highest concentration of flavonols. Among the tomato-based
      products investigated, tomato juice and tomato puree were rich in flavonols,
      containing 14-16 microgram/mL and 70 microgram/g fw, respectively. In contrast to
      fresh tomatoes, most tomato-based products contained significant amounts of free
      flavonols.

PMID- 10898605
TI  - Characterization of anti-irradiation-denatured ovalbumin monoclonal antibodies.
      Immunochemical and structural analysis of irradiation-denatured ovalbumin.
AB  - Five monoclonal antibodies (OVA-01, -02, -03, -04, -06) produced against
      irradiated ovalbumin were investigated in relation to the conformational change
      in the ovalbumin molecule induced by irradiation with Cobalt-60 gamma-rays. Four
      antibodies (OVA-01, -02, -04, -06) recognized both native and irradiated
      ovalbumin, but OVA-03 reacted only with irradiated ovalbumin. These antibodies
      were classified by modified competitive ELISA, and their K(d) values were
      determined by the Klotz equation. Epitope analyses were also performed on OVA-03
      using CNBr-cleaved peptide fragments from ovalbumin, and it was confirmed that
      OVA-03 bound to the fragment corresponding to residues Val173-Met196 of the
      ovalbumin molecule that consists of internal beta-sheet strand 3A and helix F1
      containing one open turn. These results demonstrate that dramatic conformational
      changes in proteins can be induced or that some tertiary or secondary structures
      can be broken down by gamma-ray irradiation, producing new antigenic sites.

PMID- 10898606
TI  - Drying temperature effect on water vapor permeability and mechanical properties
      of whey protein-lipid emulsion films.
AB  - The water vapor permeability (WVP) and mechanical properties of whey protein
      isolate (WPI) and WPI-lipid emulsion films dried at different conditions were
      investigated. As drying temperature increased, WVPs decreased significantly.
      Significantly lower WVP was observed for emulsion films compared to WPI films.
      WPI-Beeswax (BW) and WPI-anhydrous milkfat fraction emulsion films dried at 80
      degrees C and 40% RH gave the lowest WVP compared to 25 degrees C, 40% RH and 40
      degrees C, 40% RH. A large drop in WVP of WPI-BW emulsion films was observed at
      20% BW content. The decrease in WVP for emulsion films as drying temperature
      increased could be due to change in the lipid crystalline morphology and/or lipid
      distribution within the matrix. Mechanical properties of WPI and WPI-lipid
      emulsion films, on the other hand, were not modified by drying conditions.

PMID- 10898607
TI  - Determination of ascorbigens in autolysates of various Brassica species using
      supercritical fluid chromatography.
AB  - A new method of analysis based on normal phase supercritical fluid chromatography
      (SFC) has been developed for investigation of ascorbigens [2-C-(indol-3-ylmethyl)
      beta-L-xylo-3-hexulofuranosonic acid gamma-lactone derivatives]. This method has
      been adapted to preparative isolation and quantitative determinations of
      individual ascorbigens comprising ascorbigen, neoascorbigen, and 4
      methoxyascorbigen. The structures of these compounds have been revealed from 1D
      ((1)H, (13)C) and 2D (COSY, HMQC, HMBC) NMR experiments. The developed SFC method
      had an acceptable linearity for the ascorbigens with correlation coefficients
      (R(2)) > 0.9995 (n = 10) in the range of 0.13-4.9 nmol injected, detection limits
      were below 13 pmol, retention time stabilities were excellent, and relative
      response factors have been determined. The SFC method has been used for
      determination of ascorbigens produced during autolysis of indol-3
      ylmethylglucosinolates in various Brassica vegetables and rapeseed seedlings.
      Generally, 30-60% of the indol-3-ylmethylglucosinolates in the plants were
      transformed into ascorbigens, with the concentration in autolysates varying from
      0.51 +/- 0.002 to 3.72 +/- 0.21 micromol/g of dry weight (DW) for ascorbigen,
      from 0.05 +/- 0.01 to 2.42 +/- 0.23 micromol/g of DW for neoascorbigen, and from
      0.03 +/- 0.002 to 0.84 +/- 0.07 micromol/g of DW for 4-methoxyascorbigen.

PMID- 10898608
TI  - Simplified process for soybean glycinin and beta-conglycinin fractionation.
AB  - A simplification of the pilot-plant scale modified Nagano method yielding two
      protein fractions, glycinin and beta-conglycinin, by pH adjustment and
      ultrafiltration membrane separation was developed and compared with our pilot
      plant-scale modified Nagano procedure and with a soy protein isolate pilot-plant
      procedure as our reference process. Two protein fractions, glycinin and beta
      conglycinin, were produced from our simplified process and compared to the three
      protein fractions, glycinin, beta-conglycinin, and an intermediate protein
      mixture, produced with the modified Nagano method. The pilot-plant yields of
      glycinin, beta-conglycinin, and intermediate mixture fractions from the modified
      Nagano method were 9.4, 10.3, and 4.8% [dry basis (db)], respectively. The yield
      of glycinin fraction of the simplified method was 9.7% (db), and it had a protein
      content and purity similar to those obtained with the modified Nagano method. The
      yield of the beta-conglycinin fraction was 19.6% (db), which was twice that of
      the modified Nagano process. The protein content of beta-conglycinin was 91.6%
      (db), and the purity was 62.6% of the protein content, which was 9% lower in
      purity than the modified Nagano method. Process optimization of the simplified
      method suggested the best operating conditions for the membrane filtration system
      were 20-25 psi inlet pressure and 200-250 L/min ultrafiltration recirculation
      speeds.

PMID- 10898609
TI  - Characterization of two Acacia gums and their fractions using a langmuir film
      balance.
AB  - The mechanical properties of monolayers from two Acacia gums [Acacia senegal (L.)
      Willd. and Acacia seyal Del.] and their three fractions isolated by hydrophobic
      interaction chromatography were studied with a Langmuir film balance to obtain a
      more complete understanding of their action mode. The analysis of compression
      isotherms revealed that A. senegal gums globally exhibit better interfacial
      properties than A. seyal ones. The behavior of the whole gums appeared to be
      strongly influenced by their arabinogalactan-protein complex.

PMID- 10898610
TI  - Enzymatic degradation of cell wall polysaccharides from mango (Mangifera indica
      L.) puree.
AB  - Ripe mango puree (Smith cultivar) was treated with fungal polysaccharidases
      containing pectinolytic, hemicellulolytic, and cellulolytic activities for 2 h at
      50 degrees C. A loss of 30% of the cell wall material (CWM) was measured. CWM
      polysaccharides were hydrolyzed to varying degrees: 88, 65, and 65% of,
      respectively, galacturonic acid-, arabinose-, and rhamnose-containing polymers
      were hydrolyzed, whereas 50% of cellulose was degraded. After 30 min of
      treatment, the ethanol precipitation test on the serum was negative, indicating
      that pectic substances were rapidly hydrolyzed. Oligogalacturonic acids (degree
      of polymerization, 1-12) were observed in the serum. A viscosity drop of 90% was
      measured after 2 h, confirming the dominant role of pectic substances in puree
      viscosity.

PMID- 10898612
TI  - Emulsifying ability of porphyran prepared from dried nori, Porphyra yezoensis, a
      red alga.
AB  - A suspension of low-quality dried nori processed from Porphyra yezoensis, a red
      alga, was autoclaved at 120 degrees C for 30 min, and from the supernatant, five
      preparations of porphyran of differing molecular masses and chemical compositions
      were obtained by preprecipitation with ethanol at stepwise-increasing
      concentrations of 50 and 67% followed by size-exclusion chromatography. The
      porphyran preparations exhibited a high emulsifying activity index and high
      emulsion stability over a wide range of pH and temperature and also in the
      presence of sodium chloride. An adequately high coefficient of correlation
      between the median diameter of oil droplets and their 3,6-anhydrogalactose
      content suggests that 3,6-anhydrogalactose could take part in emulsification with
      porphyran.

PMID- 10898611
TI  - Galactosylpinitols isolated from vetch (Vicia villosa roth.) seeds.
AB  - Three alpha-galactosides of D-pinitol: 1D-O-(alpha-D-galactopyranosyl)-(1-->2)-4
      O-methyl-chiro-inositol, 1, 1D-O-alpha-D-galactopyranosyl-(1-->6)-O-alpha-D
      galactopyranosyl-(1- ->2)-4-O-methyl-chiro-inositol, 2, and 1D-O-alpha-D
      galactopyranosyl-(1-->6)-O-alpha-D-galactopyranosyl-(1-- >6)-O-alpha-D
      galactopyranosyl-(1-->2)-4-O-methyl-chiro-inositol, 3, present in vetch seeds,
      were isolated, purified, and quantitatively determined using column and high
      resolution gas chromatography. Their structures were established by (1)H and
      (13)C NMR 1D and 2D techniques.

PMID- 10898613
TI  - Accumulation of PAL transcript and PAL activity as affected by heat-conditioning
      and low-temperature storage and its relation to chilling sensitivity in mandarin
      fruits.
AB  - The effects of different periods of heating at 37 degrees C on phenylalanine
      ammonia-lyase (PAL) and how this relates to chilling tolerance was investigated
      in fruits of the chilling-sensitive Fortune mandarin. All effective heat
      conditioning treatments caused an early and transient increase in PAL mRNA and
      PAL activity. Conditioning fruits at 37 degrees C for 1 or 2 days prevented the
      manifestation of chilling symptoms but not the accumulation of PAL mRNA and PAL
      activity observed in untreated fruits. In fruits conditioned for 3 days, cold
      induced damage and PAL activity were also suppressed but not the accumulation of
      PAL transcript upon subsequent storage at 2 degrees C. Storage of 3-day-heated
      fruits at a nonchilling temperature (12 degrees C) induced an early and transient
      increase in both PAL mRNA and PAL activity. High levels of PAL transcript and PAL
      activity were detected in freshly harvested fruits of a chilling-resistant
      mandarin (Hernandina) that decreased upon cold storage at 2 degrees C in heat
      treated and nontreated fruits. These results indicate that sensitivity of
      mandarins to chilling correlates with low constitutive levels of PAL mRNA and PAL
      activity and with the inducibility of both upon exposure to low temperatures.

PMID- 10898614
TI  - Purification and characterization of polyphenol oxidase from banana (Musa
      sapientum L.) pulp.
AB  - Polyphenol oxidase (EC 1.10.3.1, PPO) in the pulp of banana (Musa sapientum L.)
      was purified to 636-fold with a recovery of 3.0%, using dopamine as substrate.
      The purified enzyme exhibited a clear single band on polyacrylamide gel
      electrophoresis (PAGE) and sodium dodecyl sulfate (SDS)-PAGE. The molecular
      weight of the enzyme was estimated to be about 41000 and 42000 by gel filtration
      and SDS-PAGE, respectively. The enzyme quickly oxidized dopamine, and its K(m)
      value for dopamine was 2.8 mM. The optimum pH was at 6.5, and the enzyme activity
      was stable in the range of pH 5-11 at 5 degrees C for 48 h. The enzyme had an
      optimum temperature of 30 degrees C and was stable even after a heat treatment at
      70 degrees C for 30 min. The enzyme activity was completely inhibited by L
      ascorbic acid, cysteine, sodium diethyldithiocarbamate, and potassium cyanide.
      Under a low buffer capacity, the enzyme was also strongly inhibited by citric
      acid and acetic acid at 10 mM.

PMID- 10898615
TI  - Inhibition of xanthine oxidase and suppression of intracellular reactive oxygen
      species in HL-60 cells by theaflavin-3,3'-digallate, (-)-epigallocatechin-3
      gallate, and propyl gallate.
AB  - The inhibitory effects of five tea polyphenols, namely theaflavin (TF1),
      theaflavin-3-gallate (TF2), theaflavin-3,3'-digallate (TF3), (-)-epigallocatechin
      3-gallate (EGCG), and gallic acid, and propyl gallate (PG) on xanthine oxidase
      (XO) were investigated. These six antioxidant compounds reduce oxidative stress.
      Theaflavins and EGCG inhibit XO to produce uric acid and also act as scanvengers
      of superoxide. TF3 acts as a competitive inhibitor and is the most potent
      inhibitor of XO among these compounds. Tea polyphenols and PG all have potent
      inhibitory effects (>50%) on PMA-stimulated superoxide production at 20
      approximately 50 microM in HL-60 cells. Gallic acid (GA) showed no inhibition
      under the same conditions. At 10 microM, only EGCG, TF3, and PG showed
      significant inhibition with potency of PG > EGCG > TF3. The superoxide scavenging
      abilities of these six compunds are as follows: EGCG > TF2 > TF1 > GA > TF3 > PG.
      PG was the most potent inhibitor of PMA-stimulated H(2)O(2) production in HL-60
      cells. The order of H(2)O(2) scavenging ability was TF2 > TF3 > TF1 > EGCG > PG >
      GA. Therefore, the antioxidative activity of tea polyphenols and PG is due not
      only to their ability to scavenge superoxides but also to their ability to block
      XO and related oxidative signal transducers.

PMID- 10898616
TI  - Cordycepin: selective growth inhibitor derived from liquid culture of Cordyceps
      militaris against Clostridium spp.
AB  - The growth responses of nine human intestinal bacteria to liquid culture of
      Cordyceps militaris Link. Pt. (Ascomycotina: Clavicipitaceae) collected from a
      pupa of Bombyx mori L. (Lepidoptera: Bombycidae) were examined using
      spectrophotometric and impregnated paper disk methods and compared to those of
      tetracycline and chloramphenicol, as well as those of Coptis japonica root
      derived berberine chloride. The biologically active constituent of the cultures
      was characterized as cordycepin (3'-deoxyadenosine) by spectroscopic analysis.
      This compound revealed potent growth-inhibiting activity toward Clostridium
      paraputrificum and Clostridium perfringens at 10 microgram/disk without adverse
      effects on the growth of Bifidobacterium bifidum, Bifidobacterium breve,
      Bifidobacterium longum, Bifidobacterium adolescentis, Lactobacillus acidophilus,
      and Lactobacillus casei, whereas tetracycline and chloramphenicol inhibited the
      growth of these lactic acid-producing bacteria, clostridia and Escherichia coli.
      However, C. militaris-derived materials revealed no growth stimulation on the
      bifidobacteria and lactobacilli. These results may be an indication of at least
      one of the pharmacological actions of C. militaris. As a naturally occurring
      antibacterial agent, cordycepin could be useful as a new preventive agent against
      various diseases caused by clostridia.

PMID- 10898617
TI  - The effect of high hydrostatic pressure on the strawberry anthocyanins.
AB  - Color stability of fruit juice made from strawberries (Fragaria x ananassa, cv.
      Elsanta) that were subjected to high hydrostatic pressure was studied by
      measuring the anthocyanin content. High hysrostatic pressure is a method of
      preservation of food alternative to heat treatment. It is therefore essential to
      assess the impact of high pressure on color molecules. Samples were pressurized
      under 200, 400, 600, and 800 MPa for 15 min at a temperature controlled between
      18 and 22 degrees C. After application of pressure, the anthocyanin content of
      the strawberry juice was analyzed by HPLC-UV using a novel isocratic elution
      system. The high-pressure treated samples were kept at refrigerator temperature
      (4 degrees C), room temperature (20 degrees C), and 30 degrees C. Two pigments
      were identified and quantified: pelargonidin 3-glucoside and pelargonidin 3
      rutinoside. The highest stability of the anthocyanins was found when strawberries
      were stored at a temperature of 4 degrees C. High-pressure treatment at 800 MPa
      led to the lowest losses, at 4 degrees C.

PMID- 10898618
TI  - Antioxidant activity of various fractions of non-tannin phenolics of canola
      hulls.
AB  - Cyclone canola hulls were extracted with 70% (v/v) acetone. The dried crude
      extract was dissolved in ethanol and fractionated on a Sephadex LH-20 column
      using 95% (v/v) ethanol as the mobile phase. Five major fractions were isolated
      according to the UV absorption. All fractions exhibited marked antioxidant
      activity in a beta-carotene-linoleate model system. Fractions I and II showed the
      best preventive effect against the bleaching of beta-carotene. The scavenging
      effect of fractions I, III, and V, at 1 mg, on alpha, alpha-diphenyl-beta
      picrylhydrazyl (DPPH) radical was 67.4%, 80.7%, and 63.3%, respectively.
      Fractions II and IV showed weak DPPH scavenging effects. The reducing power of
      phenolics present in fractions IV and V was greater than that of fractions I-III,
      and the observed data correlated well (r(2) = 0.937; P = 0.007) with the total
      content of phenolics present in each fraction.

PMID- 10898619
TI  - Antioxidant properties of water extracts from Cassia tora L. in relation to the
      degree of roasting.
AB  - The antioxidant properties of water extracts from Cassia tora L. (WECT) prepared
      under different degrees of roasting were investigated. The water extracts of
      unroasted C. tora L. (WEUCT) showed 94% inhibition of peroxidation of linoleic
      acid at a dose of 0.2 mg/mL, which was higher than that of alpha-tocopherol
      (82%). Water extracts prepared from C. tora L. roasted at 175 degrees C for 5 min
      and at 200 degrees C for 5 min exhibited 83% and 82%, respectively, inhibition of
      linoleic acid peroxidation. This result indicated that the antioxidant activities
      of WECT decreased with longer roasting time or higher roasting temperature. The
      IC(50) of WEUCT in liposome oxidation induced by the Fenton reaction was 0.41
      mg/mL, which was higher than that of alpha-tocopherol (IC(50) = 0.55 mg/mL).
      WEUCT also exhibited good antioxidant activity in enzymatic and nonenzymatic
      microsome oxidative systems. The water extracts of roasted C. tora L. increased
      in the degree of browning and produced chemiluminescence when compared with the
      unroasted sample. However, the total polyphenolic compounds of WECT decreased
      after the roasting process finished. In conclusion, the decrease in the
      antioxidant activity of water extracts from roasted C. tora L. might have been
      due to the degradation of Maillard reaction products and the decrease of
      polyphenolic compounds.

PMID- 10898620
TI  - Monitoring glycation of lysozyme by electrospray ionization mass spectrometry.
AB  - Electrospray ionization mass spectrometry (ESI-MS) was used to study the
      glycation of lysozyme by D-glucose (LZM-G) and by D-fructose (LZM-F) under dry
      heating conditions in the presence and in the absence of oxygen. ESI-MS proved to
      be a precise method for monitoring protein glycation with respect to following
      the extent of glycation and changes in the glycoconjugate profile with time. The
      ESI-MS spectrum of glycated LZM revealed a heterogeneous distribution of
      glycoforms of LZM at different reaction stages. D-Glucose showed a higher level
      of reactivity with the amino groups of LZM than D-fructose, both in the presence
      and in the absence of oxygen. The presence of oxygen in the reaction system
      induced oxidative side reactions, which competed with and slowed the initial rate
      of formation of Amadori or Heyns products. The more reactive glycoxidation
      products formed during the initial stages of incubation in the presence of oxygen
      accelerated the rate of glycation during the later stages of incubation and
      increased the involvement of arginine residues of LZM in the glycation reaction.
      The interaction between the initial glycoxidation product(s) of the reducing
      sugars and intact lysozyme during the later stages of incubation was observed by
      the appearance of a different cluster of glycoconjugates in the mass spectrum
      during the latter stages of incubation. The molecular weight differences between
      the molecular ions of the new cluster of glycoconjugates are consistent with the
      formation of D-glucosone from the autoxidation of D-glucose or from the oxidative
      cleavage of the glucose-lysozyme imine adduct in the lysozyme-glucose system. The
      effect of oxygen-induced glycoxidation on the glycation reaction was also more
      pronounced in the LZM-G system compared with that in the LZM-F system.

PMID- 10898621
TI  - Interactions among protein molecules in freeze-gel of soymilk and protein
      structures in heated soymilk during cooling.
AB  - To estimate the interactions forming in soymilk freeze-gel, lyophilized gel was
      extracted successively with various solvents. A mixture of urea, sodium dodecyl
      sulfate (SDS), and 2-mercaptoethanol (2-ME) dissolved the proteins effectively.
      The thiol-disulfide exchange reactions and hydrophobic interactions were shown to
      have a complex relation with a three-dimensional network. The addition of SDS or
      2-ME resulted in an incomplete gel or no precipitation of soymilk. In our
      previous paper (Shimoyamada et al. Food Sci. Technol. Res. 1999, 5, 284-288), the
      significance of precooling to form small, homogeneously distributed ice crystals
      in soymilk was reported. In this study, precooling was shown to maintain the
      partially denatured structures of soybean proteins in soymilk that had unfolded
      due to heat treatment. These phenomena were considered to be other important
      functions of precooling in freeze-gelation.

PMID- 10898622
TI  - Biogenic amines occurrence in wine. Amino acid decarboxylase and proteolytic
      activities expression by Oenococcus oeni.
AB  - This work deals with the study of the proteolytic and amino acid decarboxylase
      activities of selected Oenococcus oeni isolates and the effect of yeast autolysis
      on biogenic amines production in wine. A total of 220 isolates of O. oeni were
      tested for decarboxylase and proteolytic activity. Only six isolates showed both
      activities, but only after a period of adaptation in a growth medium containing
      wine. The results reported on this paper show that proteolytic activity was
      dependent on medium composition and bacterial growth phase. It can be assumed
      that the ability of O. oeni to use wine peptides and to produce biogenic amines
      is not a constant characteristic of this species, and enzymatic system expression
      appears to be closely dependent on nutritional and energetical composition of the
      medium. It also seems to be strain dependent and not widespread among this
      bacterial community.

PMID- 10898623
TI  - Antioxidant activity of malt rootlet extracts.
AB  - To improve the malt rootlet value, the antioxidant potentialities of this
      byproduct of the malting industry have been analyzed. Three extracts have been
      considered from the points of view of dry matter yield, level of antioxidant
      compounds, and efficiency and cost of the extraction protocols. They respectively
      contain rootlet oil, free phenolic compounds, and bound phenolic compounds. The
      rootlet oil contains only a low quantity of tocopherols (respectively, 20.6 and
      4.2 microgram of alpha-tocopherol and gamma-tocopherol per gram of dry rootlets),
      and a weak antioxidant activity, evaluated in a stripped corn oil by following
      spectrophotometrically the conjugated dienes, has been pointed out. The bound
      compound extract presents a good antioxidant power mainly due to the presence of
      trans-ferulic and trans-p-coumaric acids, but the dry matter yield is low (2%).
      The free compound extract has a good antioxidant power, and the valuable dry
      matter, mainly composed of proteins (52%), sugars (33%), and reducing compounds
      (5.5%), has a yield of 12%. The mixing of bound and free compound extracts
      presents an antagonistic effect on the antioxidant power, but a synergistic
      effect has been pointed out for the mixing of alpha-tocopherol and free compound
      extract.

PMID- 10898624
TI  - LC/MS analysis of cyclohexanedione oxime herbicides in water.
AB  - A multiresidue method for the determination of alloxydim (methyl 2, 2-dimethyl-4,
      6-dioxo-5-[1-[2-propenyloxy)amino]butylidene]cyclohexanec arb oxylate), clethodim
      (E, E)-(+/-)-2-[1-[[3-chloro-2-propenyl)oxy]imino]propyl]-5-[2-(ethylthio
      )propyl]-3-hydroxy-2-cyclohexen-1-one), sethoxydim ((+/-)-2-[1
      (ethoxyimino)butyl]-5-[2-ethylthio)propyl]-3-hydroxy-2 -cy clohexen-1-one), and
      two metabolites, clethodim sulfoxide ((E, E)-(+/-)-2-[1-[[3-chloro-2
      propenyl)oxy]imino]propyl]-5-[2-(ethylsulf inyl)propyl]-3-hydroxy-2-cyclohexen-1
      one) and sethoxydim sulfoxide ((+/-)-2-[1-(ethoxyimino)butyl]-5-[2
      ethylsulfinyl)propyl]-3 -hydroxy- 2-cyclohexen-1-one), in water by high
      performance liquid chromatography/electrospray/mass spectrometry (LC/ES/MS) is
      reported. River water and distilled water were spiked at 0.08 and 0.8 microgram
      L(-1) with all three herbicides, which were then extracted from the water by
      C(18)-SPE (SPE = solid-phase extraction). The herbicides and metabolites were
      quantified and confirmed using selected ion monitoring. The percent recoveries of
      the herbicides from water spiked at 0.8 microgram L(-1) were as follows:
      alloxydim, 117 +/- 11%; clethodim, 96 +/- 14%; sethoxydim, 89 +/- 13%. There was
      no evidence of oxidation of clethodim and sethoxydim during the extraction to
      their respective sulfoxides. The limit of quantitation was <0.1 microgram L(-1).
      We have shown that we can analyze and confirm three cyclohexanedione oxime
      herbicides and two metabolites in water by LC/ES/MS. This multiresidue method
      should also be appropriate for other cyclohexanedione oximes.

PMID- 10898625
TI  - Sensitive spectrophotometric assay for 3-hydroxy-substituted flavonoids, based on
      their binding with molybdenum, antimony, or bismuth.
AB  - A sensitive spectrophotometric assay has been developed for flavonoids based on
      their binding with molybdenum, antimony, or bismuth. Acetylation of the hydroxyl
      group of flavonoids abolished metal binding, thus suggesting a direct role of the
      hydroxyl groups. From a comparison of several related flavonoids differing in the
      position of hydroxyl substitutions, the hydroxyl group at position 3 was found to
      be an important requirement for the formation of a yellow complex. This flavonoid
      metal complex showed that a specific and significant bathochromic shift in the
      visible spectrum of the native flavonoid and the corresponding lambda(max) value
      was used for the colorimetric assays with different metal salts. The molybdenum
      complex was found to yield higher absorbance compared to antimony and bismuth
      complexes of various flavonoids. The present method offers a sensitive assay in
      the 5-25 nM range for these flavonoids and gave comparable results with HPLC
      quantitative determination.

PMID- 10898626
TI  - MALDI-TOF MS quantification of coccidiostats in poultry feeds.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) is a relatively new technique that is having a great impact on
      analyses. This study is the first to demonstrate the use of linear MALDI-TOF MS
      to identify and quantify coccidiostats in poultry feeds. 2,5-Dihydroxybenzoic
      acid (DHB) was found to be the best matrix. In MALDI-TOF MS, coccidiostats form
      predominantly [M + Na](+) ions, with additional small amounts of [M + K](+) and
      [M - H + 2Na](+) ions, and no obvious fragment ions. Salinomycin and narasin were
      unstable in the concentrated DHB matrix solution but were stable when dried on
      the MALDI-TOF MS probe. A simple fast Sep-pak C18 cartridge purification
      procedure was developed for the MALDI-TOF MS quantification of coccidiostats in
      poultry feeds. The MALDI-TOF MS limit of detection for lasalocid, monensin,
      salinomycin, and narasin standards was 251, 22, 24, and 24 fmol, respectively.
      The method detection limit for salinomycin and narasin in poultry feeds was 2.4
      microgram/g.

PMID- 10898627
TI  - Voltammetric iodometric titration of ascorbic acid with dead-stop end-point
      detection in fresh vegetables and fruit samples.
AB  - The present work describes a method for determining ascorbic acid, which combines
      iodometry with a voltammetric technique to detect the end point of the titration.
      In addition, the validity of the method applied to natural vegetable or fruit
      samples was assessed. The results were compared with those obtained by an
      accurate method such as HPLC using UV detection. Similar values of ascorbic acid
      for different natural samples were obtained by means of this approach (p > 0.05).
      The limit of quantification was 0.1 mg. This technique presents the advantage of
      other electroanalytical methods such as avoiding filtration or
      ultracentrifugation steps, with the additional benefit of using the platinum
      electrodes, which are routinely used in the laboratory. These facts allow a rapid
      and efficient quantification of ascorbic acid with very low cost of reagents and
      equipment.

PMID- 10898629
TI  - Development of a sensitive ELISA for the determination of fumonisin B(1) in
      cereals.
AB  - Monoclonal fumonisin B(1) antibodies with high titer were raised by using FB(1)
      glutaraldehyde-keyhole limpet hemocyanin immunogen prepared by a short cross
      linker reagent (glutaraldehyde). Mean cross-reactivities of the selected
      monoclonal antibody for FB(1), FB(2), and FB(3) were 100, 91.8, and 209%,
      respectively; no reactivity was found with hydrolyzed fumonisin. A direct,
      competitive enzyme-linked immunosorbent assay for the quantitative determination
      of FB(1) in cereals has been developed with this antibody. Fifty percent
      acetonitrile-based solvent with some additives was used for extraction of
      cereals, and the diluted extracts were used without cleanup in the test. The mean
      within-assay and interassay coefficients of variation for the standard curve were
      <10%. The measuring range of this test is 10-500 ng/g, with a detection limit of
      7.6 ng/g FB(1). The toxin recovery from cereals infected with 50-200 ng/g of
      FB(1) varied between 61 and 84%. According to the comparable results of naturally
      infected maize samples, this test proved to be suitable for the rapid screening
      of food and feed samples for the presence of FBs.

PMID- 10898628
TI  - Effect of a pilot washing system on dicofol levels in orange matrix.
AB  - An efficient analytical method is described for the analysis of dicofol residues
      in pulp and orange peel. Samples are mixed with Celite and transferred to
      chromatographic columns prepacked with silica gel. Dicofol is eluted with ethyl
      acetate, and the extracts are analyzed by gas chromatography with electron
      capture detection. Mean recoveries for dicofol at levels of 0.5, 2.0, 5.0, and 10
      mg/kg ranged from 87 to 95% with relative standard deviation values between 2.6
      and 9.0%. To investigate the effect of a pilot washing system on dicofol residues
      in oranges, the analytical procedure was applied to samples submitted to
      different treatments with commercial formulations under field and laboratory
      conditions. The orange samples with and without washing were analyzed in
      duplicate, and the results indicated that washing under the described conditions
      did not allow a complete removal of dicofol residues from orange peel.

PMID- 10898630
TI  - Synthesis of (Diethyl-d(10)) coumaphos and related compounds.
AB  - Two deuterated insecticides were prepared for use as internal standards for gas
      liquid chromatographic-mass spectrometric analyses. Diethyl chlorothiophosphate
      d(10) was prepared by reaction of ethanol-d(6) with P(2)S(5) to give labeled
      diethyldithiophosphoric acid, followed by chlorination. Treatment of the acid
      chloride with 3-chloro-4-methyl-7-hydroxycoumarin and potassium carbonate in
      acetone at reflux gave labeled coumaphos. An analogous reaction with 4-methyl-7
      hydroxycoumarin gave labeled potasan, and the technique should be usable for
      synthesis of labeled forms of other dialkyl thiophosphate insecticides.

PMID- 10898631
TI  - Direct and highly species-specific detection of pork meat and fat in meat
      products by PCR amplification of mitochondrial DNA.
AB  - Highly species-specific primers for pork D-loop mtDNA have been designed. Use of
      these and restrictive PCR amplification conditions has improved a reliable and
      rapid method for detecting a PCR-amplified 531 bp band from pork. It has been
      proved useful for detecting both pork meat and fat in meat mixtures, including
      those dry-cured and heated by cooking. Absence of response in PCR-amplified
      samples or mixtures from bovine, ovine, chicken, and human was also demonstrated.
      Furthermore, wild boar and pork samples can be also easily distinguished by a
      simple AvaII restriction analysis.

PMID- 10898632
TI  - Mold occurrence and aflatoxin B(1) and fumonisin B(1) determination in corn
      samples in Venezuela.
AB  - Fumonisins are mycotoxins produced mainly by Fusarium moniliforme and Fusarium
      proliferatum, which have been associated with several animal and human diseases.
      Aflatoxins are hepatotoxic, mutagenic, and teratogenic metabolites produced by
      Aspergillus flavus and Aspergillus parasiticus. Both have been reported at high
      levels in corn. This study was pursued to determine mold, aflatoxin B(1)
      (AFTB(1)), and fumonisin B(1) (FB(1)) levels in white and yellow corn. Mold
      levels were determined using potato dextrose agar and identification of the main
      genus of molds present in corn, AFTB(1) levels by immunoaffinity chromatography,
      and FB(1) levels by a Bond-Elut SAX cartridge and HPLC. AFTB(1) an

PMID- 10898633
TI  - Fagopyritols, D-chiro-inositol, and other soluble carbohydrates in buckwheat seed
      milling fractions.
AB  - Fagopyritols are mono-, di-, and trigalactosyl derivatives of D-chiro-inositol
      that accumulate in seeds of common buckwheat (Fagopyrum esculentum Moench) and
      may be important for seed maturation and as a dietary supplement. Fagopyritols
      and other soluble carbohydrates were assayed in mature groats and 11 milling
      fractions of common buckwheat seed. Because fagopyritols are in embryo and
      aleurone tissues, differences in fagopyritol concentrations reflect varying
      proportions of these tissues in each milling fraction. Bran milling fractions
      contained 6.4 g of total soluble carbohydrates per 100 g of dry weight, 55% of
      which was sucrose and 40% fagopyritols. Flour milling fractions had reduced
      fagopyritol concentration [0.7 g/100 g of dry weight total fagopyritols in the
      dark (Supreme) flour and 0.3 g/100 g in the light (Fancy) flours]. Fagopyritol B1
      was 70% of total fagopyritols in all milling fractions. Fagopyritols were 40% of
      total soluble carbohydrates in groats of two cultivars of common buckwheat but
      21% in groats of tartary buckwheat [Fagopyrum tataricum (L.) Gaertn.], probably a
      reflection of environment and genetics. A rhamnoglucoside present in tartary
      buckwheat was not detected in common buckwheat.

PMID- 10898634
TI  - Flavonoids and other polyphenols in consumer brews of tea and other caffeinated
      beverages.
AB  - The polyphenolic, flavonoid, and caffeine compositions of four commercial tea bag
      products (typical of those used in the UK, US, continental Europe, and the Middle
      East) and beverages prepared from them under a range of typical consumer use
      conditions have been studied. Leaf composition was determined by extraction with
      aqueous methanol: the absolute compositions of all four products were remarkably
      similar in terms of most phenolic compounds. The flavonoids comprised the major
      proportion (93-94%) of the total phenolics estimated by the Folin-Ciocalteu
      method. At brew times up to 2 min the composition of the brew solids was for each
      product practically independent of brew time, with flavonoids again comprising
      the major proportion (86-88%) of the total phenolics. The efficiency of
      extraction in brewing of total phenolics, total flavonoids, catechins, and
      theaflavins was up to 35-55% of the total available in the leaf, whereas the
      flavonol and flavone glycosides and caffeine were more efficiently extracted (up
      to 55-90%). The contribution of tea to the UK adult average total dietary intake
      of flavonols and flavones was calculated to be up to 80% depending on brewing
      conditions.

PMID- 10898635
TI  - Analysis of phenolic compounds in the evaluation of commercial quince jam
      authenticity.
AB  - The phenolic compounds present in 17 samples of Portuguese commercial and three
      homemade quince jams were analyzed by reversed-phase HPLC/DAD, to determine their
      authenticity. Two different extraction methods were needed for the complete
      definition of quince jams profiles, one of them including an Amberlite XAD-2
      cleaning step. These analyses showed that all the samples presented a similar
      profile composed of at least eight identified phenolic compounds, several
      unidentified characteristic procyanidin polymers, and sodium benzoate as
      preservative of quince jams. Several samples also contained arbutin, suggesting
      that these quince jam samples were fraudulently adulterated with pear puree.

PMID- 10898636
TI  - Volatile components of green walnut husks.
AB  - Volatiles were isolated from whole green mature walnuts (Hartley variety) with
      husks still intact using dynamic headspace sweeping with trapping on Tenax. A
      total of 45 volatile compounds were identified by GC-MS. Major volatiles
      identified included (E)-4, 8-dimethyl-1,3,7-nonatriene, pinocarvone, pinocarveol,
      myrtenal, myrtenol, (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene,
      caryophyllene epoxide, verbenol, verbenone, and terpinolene. Green walnuts that
      had been infested with codling moth showed appreciably higher amounts emitted for
      (E)-4,8-dimethyl-1,3,7-nonatriene, (E, E)-4,8,12-trimethyl-1,3,7,11
      tridecatetraene, alpha- and beta-pinenes, sabinene, (E)-beta-ocimene, (E,E)-alpha
      farnesene, and linalool. The infested nuts also emitted benzyl methyl ether,
      isobutyl cyanide, and 1-nitro-3-methylbutane, compounds not found with the
      healthy nuts. Volatiles from uninfested green walnuts at the maturity stage where
      the husk was just beginning to split were also analyzed and compared.

PMID- 10898637
TI  - Content of glucosinolates in cruciferous vegetables grown at the same site for
      two years under different climatic conditions.
AB  - Individual glucosinolates (GLS) were determined in vegetables of three Cruciferae
      species: Brassica oleracea L. (white cabbage, red cabbage, Savoy cabbage,
      Brussels sprouts, cauliflower, kale, kohlrabi), Brassica rapa L. (turnip), and
      Raphanus sativus L. (red radish, black radish, and white radish) produced in two
      years. The cultivars were compared for the contents of total-, indole-, and
      aliphatic GLS. In both years, the total content of GLS was highest in black
      radish, and all examined R. sativus vegetables contained the greatest amount of
      aliphatic GLS. Neither the level nor the identity of GLS differentiated among the
      vegetables of the other cultivars grown in the same year. Comparison of the GLS
      contents of the same cultivar in two production years, which differed in
      temperature and rainfall rate, showed that low average 10-day rainfall and high
      average temperature during the vegetation period significantly increased the GLS
      content of vegetables. This suggests that the year x cultivar interaction
      modified the GLS content of vegetables.

PMID- 10898638
TI  - Determination of furan fatty acids in extra virgin olive oil.
AB  - The presence of 4 different furan fatty acids (F-acids) was detected in 18
      samples of transmethylated monovarietal extra virgin olive oil: methyl 10,13
      epoxy-11,12-dimethyloctadeca-10,12-dienoate [diMeF(9,5)], methyl 12,15-epoxy
      13,14-dimethyleicosa-12,14-dienoate [diMeF(11,5)] and both olefinic derivatives
      of diMeF(11,5) with one unsaturation on the side chains conjugated with the furan
      ring. Transmethylated oils were analyzed by normal phase high-performance liquid
      chromatography coupled on-line with capillary gas chromatography. After the gas
      chromatographic separation step, a more selective detection of F-acids was
      achieved by using a photoionization detector mounted in series with a flame
      ionization detector. The concentration of F-acids ranged between 50 ppb
      (detection limit of the method) and 2.1 ppm in the oil. The olefinic derivatives
      of diMeF(11,5) acids detected were not artifacts created during the sample
      preparation or during the chromatographic analysis.

PMID- 10898639
TI  - Identification of cysteinylated aroma precursors of certain volatile thiols in
      passion fruit juice.
AB  - Together with 3-mercaptohexan-1-ol and 3-mercaptohexyl acetate, already known to
      contribute to the aroma of passion fruit (Passiflora edulis), 3-mercapto-3
      methylbutan-1-ol and 3-mercapto-3-methylbutyl acetate have been identified for
      the first time in this fruit. 3-Mercaptohexan-1-ol and 3-mercapto-3-methylbutan-1
      ol may be produced in vitro from nonvolatile extracts of this fruit by the
      enzymatic action of a cell-free extract of Eubacterium limosum, which has a beta
      lyase activity on S-cysteine conjugates (EC 4.4.1.13). This release strongly
      suggests that these volatile thiols are present in combined form, as S-cysteine
      conjugates. It was possible to identify the precursor of 3-mercaptohexan-1-ol as
      S-(3-hexan-1-ol)-L-cysteine, in the form of trimethylsilylated derivatives from
      the juice of this fruit, using GC/MS analysis. The presence of free and combined
      forms of these volatile thiols in this fruit has now been demonstrated.

PMID- 10898640
TI  - Aroma-active compounds of miniature beefsteakplant (Mosla dianthera Maxim).
AB  - Volatile flavor compounds of miniature beefsteakplant (Mosla dianthera Maxim.)
      from Vietnam were analyzed through gas chromatography-mass spectrometry
      olfactometry (GC-MS-O). Sixty-two compounds were identified by GC-MS. Of these,
      (+/-)-carvone and (+/-)-limonene were the most abundant, followed by (Z)-limonene
      oxide, beta-caryophyllene, and alpha-humulene. Twenty aroma-active compounds were
      detected by aroma extract dilution analysis conducted on two GC columns of
      different polarities (DB-5MS and DB-Wax). The most intense aroma-active compounds
      were linalool (floral/sweet/lemon), (-)-carvone (spearminty), and 1-octen-3-one
      (mushroom/earthy). Other predominant aroma-active compounds included (Z)-3
      hexenol (grassy/leafy/metallic), (Z)-limonene oxide (lemon/floral), myrcene
      (plastic/sweet), (+)-limonene (orange/lemon), alpha-thujene (soy sauce/grassy),
      and (Z)-dihydrocarvone (spearminty/pepperminty). On the basis of the aroma
      characteristics and intensity, it was concluded that (-)-carvone was responsible
      for the characteristic aroma of miniature beefsteakplant.

PMID- 10898641
TI  - Determination of vanillin in orange, grapefruit, tangerine, lemon, and lime
      juices using GC-olfactometry and GC-MS/MS.
AB  - The presence of vanillin in orange, tangerine, lemon, lime, and grapefruit juices
      has been identified and confirmed using high-resolution GC retention index
      values, mass spectra, and aroma quality. The impact of vanillin on the flavor
      score for grapefruit juice is discussed and reported to be minimal. Vanillin
      concentrations are determined to be in the low parts-per-million range for the
      various citrus juices. The calculated concentrations in the orange, tangerine,
      lemon, lime, and grapefruit juices are 0.20, 0.35, 0.41, 0.35, and 0.60 ppm,
      respectively. Pasteurization produced an average 15% increase in the
      concentration of vanillin in grapefruit juices. Vanillin did not correlate well
      with the overall flavor score despite a rather intense signal using OSME gas
      chromatography-olfactometry software.

PMID- 10898642
TI  - Biotransformation of gamma-terpinene and (-)-alpha-phellandrene by the larvae of
      common cutworm (Spodoptera litura).
AB  - gamma-Terpinene was mixed in artificial diet at a concentration of 1 mg/g of
      diet, and the diet was fed to the last instar larvae of common cutworm
      (Spodoptera litura). Metabolites were recovered from frass and analyzed
      spectroscopically. gamma-Terpinene was transformed mainly to p-mentha-1,4-dien-7
      oic acid and p-cymen-7-oic acid (cumic acid). Similarly, (-)-alpha-phellandrene
      was transformed mainly to (4R)-p-mentha-1,5-dien-7-oic acid and p-cymen-7-oic
      acid (cumic acid). The C-7 position (allylic methyl group) of gamma-terpinene and
      (-)-alpha-phellandrene was preferentially oxidized.

PMID- 10898643
TI  - Uruguayan essential oil. 12. Composition of Nova and Satsuma mandarin oils.
AB  - The composition of the laboratory-prepared essential oils from Uruguayan Nova and
      Satsuma mandarins has been studied. The volatile fraction was analyzed by HRGC
      and HRGC/MS (quadrupole); 79 and 73 components were identified in Nova and
      Satsuma mandarin oils, respectively. The linear retention indices were calculated
      for almost all identified components on two different stationary phases. The
      enantiomeric distribution of beta-pinene, sabinene, limonene, linalool, and alpha
      terpineol was studied by multidimensional gaschromatography (MDGC).
      Polymethoxylated flavones, present in the nonvolatile residue, were analyzed by
      normal-phase HPLC.

PMID- 10898645
TI  - Alternaria mycotoxins in weathered wheat from China.
AB  - This is the first report of the natural occurrence of Alternaria mycotoxins in
      Chinese wheat. Wheat kernels were significantly invaded by Alternaria species,
      mostly A. alternata, with an average infection frequency of 87.3%. A total of 22
      samples of weathered wheat kernels from the 1998 crop, representing three
      locations in the suburbs of Beijing, China, were examined for the presence of
      Alternaria mycotoxins by high-performance liquid chromatography. Alternariol
      (AOH) was detected in 20 of 22 samples ranging between 116 and 731 microgram/kg
      (mean = 335 microgram/kg) and alternariol methyl ether (AME) at a mean level of
      443 microgram/kg (range = 52-1426 microgram/kg) in 21 samples. The presence of
      tenuazonic acid (TA), a major Alternaria toxin in terms of quantity, was detected
      in all samples analyzed at an average concentration of 2419 microgram/kg with a
      maximum of 6432 microgram/kg. All samples were free from altertoxin I and
      altenuene. Samples with high levels of AOH and AME also contain a high level of
      TA. There was significant linear regression of correlations between the levels of
      AOH over AME (r = 0.850) and total benzopyrone derivatives (AOH + AME) over TA (r
      = 0.796).

PMID- 10898644
TI  - Oxidative metabolites of the mammalian lignans enterodiol and enterolactone in
      rat bile and urine.
AB  - Recent studies have shown that the mammalian lignans enterodiol (END) and
      enterolactone (ENL) are biotransformed in vitro by hepatic microsomes from rats
      and humans to various metabolites carrying one additional hydroxy group either at
      the aromatic or at the aliphatic moiety. To clarify whether these metabolites are
      also formed in vivo, each lignan was administered intraduodenally at a dose of 10
      mg/kg of bw to bile duct-catheterized female Wistar rats and the 6 h bile
      analyzed by HPLC and GC-MS. With END-dosed rats, three products of aromatic and
      two of aliphatic monohydroxylation were found, whereas six aromatic and five
      aliphatic monohydroxylated biliary metabolites were detected after administration
      of ENL. The metabolites hydroxylated at the aromatic rings were unequivocally
      identified by comparison with synthetic reference compounds. The structures of
      the in vivo metabolites arising from aliphatic hydroxylation could not be
      completely elucidated; they were identical with some of the formerly reported
      microsomal products according to GC retention times and mass spectra. Significant
      amounts of most of the metabolites of the mammalian lignans identified in bile
      were also found in the urine of female rats after oral administration of 10 mg/kg
      of bw END or ENL and in the urine of female and male Wistar rats after they had
      been fed a diet containing 5% flaxseed. Thus, the mammalian lignans END and ENL
      give rise to several hydroxylated metabolites in vivo, which may contribute to
      the biological effects of these important food constituents.

PMID- 10898646
TI  - Nitrogen metabolism in pepper plants applied with different bioregulators.
AB  - Certain bioregulators were studied in relation to nitrogen metabolism of pepper
      plants (Capsicum annuum L. cv. Lamuyo). Plants were grown under controlled
      conditions and submitted to regular fertilization with macro- and micronutrients.
      Treatments were as follows: nontreated control (T0); fosfonutren [essential amino
      acids and micronutrients (46.9 mg L(-)(1))] (T1); biozyme [GA(3) (32.2 mg L(
      )(1)) plus IAA (32.2 mg L(-)(1)) plus zeatin (83.2 mg L(-)(1)) plus chelated
      micronutrients] (T2); and GA(3) [16 mg L(-)(1)] (T3). The concentrations of
      NO(3)(-), organic N, amino acids, and proteins, the activities of nitrate
      reductase (NR) and nitrite reductase (NiR), and finally the foliar dry weight and
      yield were analyzed. The results indicated that the application of certain
      bioregulators, such as fosfonutren (T1), which contain amino acids can cause a
      negative effect on the efficiency and utilization of NO(3)(-), resulting in a
      drastic loss in growth and yield, even under the control treatment, in which no
      bioregulator was applied. On the contrary, the application of certain
      bioregulators based principally on the combination of different hormones, as in
      the case of biozyme (T2), increased NO(3)(-) assimilation under our experimental
      conditions, due possibly to a greater availability of these bioregulators in the
      leaves and increased NR and NiR activities. This appears to explain why the T2
      treatment gave the greatest foliar dry weight and fruit yield per plant in the
      experiment.

PMID- 10898647
TI  - Use of heme iron concentrate in the fortification of weaning foods.
AB  - The purpose of this study was to evaluate the technological feasibility of
      fortifying homogenized weaning food with a porcine heme concentrate. The
      stability of iron and the organoleptic qualities of two infant weaning foods (a
      commercial homogenized nonfortified weaning food, NFWF, and the same food
      fortified with 0.5% of porcine heme concentrate, FWF) were tested throughout 8
      months of storage at room temperature and at 37 degrees C. Heme iron decreased
      with storage time; however, the proportion of this highly available iron was
      considerably higher in FWF than in NFWF. The addition of heme iron changed
      significantly the color of the weaning food measured instrumentally, although
      high temperatures and length of storage time, did not modify Lab, chroma, and hue
      angle values in both samples. Organoleptic attributes presented a marked
      stability even in NFWF stored at room temperature and 37 degrees C.

PMID- 10898648
TI  - Rheological and physicochemical properties of starches from moist- and dry-type
      sweetpotatoes.
AB  - Although starch makes up from 50 to 70% of sweetpotato (SP) dry matter, its role
      in cooked texture is unknown. The purpose of this research was to characterize
      raw starches isolated from SP cultivars and experimental selections (C/S) with a
      wide range of textural properties when cooked and to investigate the relationship
      between textural properties of the cooked roots and characteristics of the
      isolated starches. Shear stress measured by uniaxial compression of cooked SP
      cylinders served as an objective measure of SP texture. Starches were isolated
      from C/S representing three SP texture types: moist (Jewel and Beauregard);
      intermediate (NC10-28 and NC2-26); and dry (NC6-30 and NC8-22). The following
      parameters of isolated starches were measured: amylose content by colorimetric
      and differential scanning calorimetric (DSC) methods; swelling power, solubility,
      gelatinization enthalpy (DeltaH), and pasting properties by Brabender amylograph
      (BA) and rapid viscoanalyzer (RVA). Pasting temperatures for SP C/S measured by
      BA and RVA were significantly correlated. Due to high shear degradation in RVA,
      RVA viscosities of starch suspensions decreased as much as 40% during cooking at
      95 degrees C, whereas the BA viscosities changed little at this temperature.
      There were no statistically significant differences among the C/S for amylose or
      DeltaH. However, significant C/S differences in swelling power, solubility, and
      pasting properties were observed. Although differences in some rheological and
      physical properties were observed for C/S starches, shear stress was
      statistically correlated only with DSC onset temperature (r = 0.78), indicating
      that factors other than the properties measured on isolated starches are mainly
      responsible for the texture of cooked SP C/S.

PMID- 10898649
TI  - Properties of chemically and physically treated wheat gluten films.
AB  - Chemical (vapors of formaldehyde), physical (temperature, UV and gamma
      radiation), and aging treatments were applied to wheat gluten films. Changes in
      film mechanical properties, water vapor permeability, solubility, and color
      coordinates were investigated. An aging of 360 h led to a 75 and 314% increase in
      tensile strength and Young's modulus, respectively, and a 36% decrease in
      elongation. Severe thermal (above 110 degrees C, 15 min) and formaldehyde
      treatments highly improved the mechanical resistance of the films. Under these
      conditions, up to 376 and 654% increase in tensile strength and Young's modulus
      and up to 66% decrease in elongation have been observed. Water solubility was
      only slightly modified, whereas water vapor permeability was not affected. Color
      coordinates of films heated above 95 degrees C changed to a great extent. An
      almost total insolubilization of proteins in sodium dodecyl sulfate occurred for
      heat- and formaldehyde-treated films, due to the modification of protein network
      leading to changes in properties of the films.

PMID- 10898650
TI  - Effect of high-temperature degradative processes on ketocarotenoids present in
      paprika oleoresins.
AB  - Carotenoid pigments in six commercial oleoresins, qualitatively uniform in
      pigment composition, were thermodegraded to determine the degradation kinetics in
      the two (red and yellow) isochromic fractions, structurally differentiated by the
      presence or absence of keto groups. The different rate of degradation of total
      pigment indicates that the oily medium modulates the degradation reaction
      differently, so that each oleoresin shows a different stability. However, in all
      the oleoresins, the red pigment fraction is degraded at a higher rate than the
      yellow. Arrhenius curves reveal an isokinetic temperature (T(isok))
      distinguishing two zones in which the degradation process has a different effect
      on each fraction. At temperatures above T(isok), degradation is preferentially
      toward the red fraction, while at lower temperatures, it is toward the yellow
      fraction. An isokinetic point between the two pigment fractions means that the
      thermal conditions at which the stability of the system is to be determined must
      be stated, as such conditions produce a different effect on each fraction.

PMID- 10898651
TI  - Carotenoid content of the varieties Jaranda and Jariza (Capsicumannuum L.) and
      response during the industrial slow drying and grinding steps in paprika
      processing.
AB  - Fruits of the pepper varieties Jaranda and Jariza (Capsicum annuum L. ) ripen as
      a group, enabling a single harvesting, showed a uniform carotenoid content that
      is high enough (7.9 g/kg) for the production of paprika. The drying system at
      mild temperature showed that fruits with moisture content of 85-88% generated a
      dry product with carotenoid content equal to or higher than the initial one.
      Those high moisture levels allowed the fruits to have a longer period of
      metabolic activity, increasing the yellow fraction, the red fraction, or both as
      a function of what biosynthetic process was predominant. This fact indicates
      under-ripeness of the fruits in the drying step. The results obtained allow us to
      establish that both varieties, Jaranda and Jariza, fit the dehydration process
      employed, yielding a dry fruit with carotenoid concentration similar to that the
      initial one. During the grinding step of the dry fruit, the heat generated by the
      hammers of the mill caused degradation of the yellow fraction, while the red
      fraction is maintained. The ripeness state of the harvested fruits and the
      appropriateness or severity of the processing steps are indicated by the ratio of
      red to yellow (R/Y) and/or red to total (R/T) pigments, since fluctuations in
      both fractions and in total pigments are reflected in and monitored by these
      parameters.

PMID- 10898652
TI  - Metabolism and fate of [(14)C]ethametsulfuron-methyl in rutabaga (Brassica
      napobrassica Mill).
AB  - The metabolism and fate of ethametsulfuron-methyl ?methyl 2-[[[[[4-ethoxy-6
      (methylamino)-1,3, 5-triazin-2-yl]amino]carbonyl]amino]sulfonyl]benzoate? in
      rutabaga were investigated. After 72 h, absorption and translocation of
      [(14)C]ethametsulfuron-methyl in rutabaga did not change for the duration of the
      study (50 days). Less than 4% of recovered radioactivity was present in the
      rutabaga root. Ethametsulfuron-methyl was metabolized through a proposed unstable
      alpha-hydroxy ethoxy intermediate that dissipated 3 days after treatment to two
      major metabolites, O-desethylethametsulfuron-methyl and N-desmethyl-O
      desethylethametsulfuron-methyl, as determined by liquid chromatography-mass
      spectrometry. It was estimated that at a spray dose of 30 g of active ingredient
      ha(-)(1) and a harvest weight of 0.5 kg, the edible portion of the rutabaga root
      would contain no ethametsulfuron-methyl and approximately 1.3 ppb total of both
      identified metabolites. Residue analysis and toxicological assessment show that
      ethametsulfuron-methyl and its metabolites should pose little or no risk to
      consumers of rutabagas.

PMID- 10898653
TI  - Metabolism-based resistance of a wild mustard (Sinapis arvensis L.) biotype to
      ethametsulfuron-methyl.
AB  - Under controlled-environment conditions, ethametsulfuron-methyl doses that
      inhibited growth by 50% (ED(50)) were >100 and <1 g of active ingredient (ai) ha(
      )(1) for ethametsulfuron-methyl-resistant (R) and -susceptible (S) wild mustard,
      respectively. There were no differences between the two biotypes with regard to
      absorption and translocation of the herbicide. Three days after treatment,
      approximately 90, 5, and 2% of the applied [(14)C]ethametsulfuron-methyl was
      found in the treated leaf, foliage, and roots of each biotype, respectively.
      Acetolactate synthase extracted from the two biotypes was equally sensitive to
      both ethametsulfuron-methyl and chlorsulfuron. These results indicate that
      resistance was not due to differences in the target site, absorption, or
      translocation. However, ethametsulfuron-methyl was metabolized more rapidly in
      the R than the S biotype. Approximately 82, 73, 42, 30, and 17% of the recovered
      radioactivity remained as ethametsulfuron-methyl in R wild mustard 3, 6, 18, 48,
      and 72 h after treatment, respectively. Conversely, 84, 79, 85, and 73% of the
      (14)C was ethametsulfuron-methyl in the S biotype 12, 24, 48, and 72 h after
      treatment, respectively. On the basis of these results, it is proposed that
      resistance is due to enhanced metabolism of ethametsulfuron-methyl in the R
      biotype.

PMID- 10898654
TI  - Residue levels, decline curves, and plantation distribution of procymidone in
      green beans grown in greenhouse.
AB  - Residue levels and degradation rates of procymidone residues were studied in
      green beans grown in a greenhouse. Experiments were planned to also assess the
      influence of planting density on the behavior of procymidone residues on this
      type of crop. The study was carried out in four random blocks considering three
      sub-blocks of different planting densities into each block. Plants were sprayed
      with Sumisclex 50 WP (1077.5 g of ai/ha) 52 days after the transplantation, and
      sampling was carried out daily during two different periods of 6 and 5
      consecutive days, respectively, around the two harvest days (days 12 and 28 after
      the treatment). Residue levels of procymidone were determined by using the Luke
      extraction method and GC-NPD. The average residue levels of procymidone in the
      overall planting (mean of 12 determinations) were below 2 mg/kg (European maximum
      residue limit) for all the sampling days, obtaining values of 1.01 +/- 0.55 and
      0.37 +/- 0.10 mg/kg, respectively, at the two harvest days. The decline behavior
      of procymidone residues in the overall plantation and in each block could be
      described as a pseudo-first-order reaction, obtaining half-life values (t(1/2))
      of 10-11 days in all cases. The calculated residue level at the preharvest time
      (5 days) in the overall plantation was 1.7 mg/kg, but this value in the blocks
      depended on the block position along the greenhouse and ranged from 2.3 to 0.9
      mg/kg. In this work, additional data on the residual behavior of the fungicide
      pyrazophos in green beans were also obtained.

PMID- 10898655
TI  - Synthesis and herbicidal activity of N-oxide derivatives.
AB  - As part of an ongoing program on the chemistry and biological activity of N-oxide
      containing molecules, a number of novel 1,2, 5-oxadiazole N-oxide, benzo[1,2
      c]1,2,5-oxadiazole N-oxide, and quinoxaline N,N'-dioxide derivatives were
      synthesized and evaluated for their herbicidal activity. Many of these compounds
      exhibited moderate to good herbicidal pre-emergence activity against Triticum
      aestivum. Dose-response studies were done on the more representative compounds
      (12, 20, and 26). The most active compound, butylcarbamoylbenzo[1,2-c]1,2,5
      oxadiazole N-oxide, 26, displayed herbicidal activity at concentrations as low as
      24 g/ha.

PMID- 10898657
TI  - Composition and some biological activities of the essential oil of Callicarpa
      americana (L.).
AB  - The essential oil profile of Callicarpa americana was examined. Samples were
      collected from Lafayette county in north central Mississippi, and GC-MS data and
      retention indices were used to identify 67 oil components. Humulene epoxide II
      (13.9%), alpha-humulene (10.0%), 7-epi-alpha-eudesmol (9.4%), beta-pinene (8.8%),
      and 1-octen-3-ol (8.5%) were the major components of the steam-distilled oil. The
      oil was selectively toxic toward the cyanobacterium Oscillatoria perornata
      compared to Oscillatoria agardhii and the green alga Selenastrum capricornutum,
      with complete growth inhibition at 28.5 microgram/mL. The oil was only mildly
      phytotoxic and antifungal.

PMID- 10898656
TI  - Natural and synthetic podolactones with potential use as natural herbicide
      models.
AB  - A collection of 11 natural and synthetic podolactones have been tested as
      allelochemicals in a range between 10(-4) and 10(-9) M, and their potential use
      as natural herbicide models is discussed. Their effects on the germination and
      growth of the dicots Lactuca sativa (cv. Nigra and cv. Roman), Lepidium sativum,
      and Lycopersicon esculentum and the monocots Allium cepa, Hordeum vulgare, and
      Triticum aestivum as standard target species have been studied. An important
      inhibitory effect on the germination and growth of all tested species (average =
      90%) was produced by compounds 9-11 at 10(-4) M. The specific structural
      requirements related to their activities are studied. On the basis of these
      results, their use as potential natural herbicide models is proposed.

PMID- 10898658
TI  - Pathways for the hydrolysis of phorate: product studies by (31)P NMR and GC-MS.
AB  - A new intramolecular mechanism is proposed for the hydrolysis of phorate. (31)P
      NMR was used to study the formation of P-containing products of phorate
      hydrolysis in situ. When hydrolysis was followed by (31)P NMR, a dominant P
      containing product was found and was identified to be diethyl dithiophosphate
      using methylation and GC-MS. Combining the data from phorate hydrolysis at three
      different temperatures, thermodynamic parameters were calculated. The
      contributions of various possible pathways to phorate hydrolysis are discussed.

PMID- 10898659
TI  - Adsorption and mobility of linuron in soils as influenced by soil properties,
      organic amendments, and surfactants.
AB  - Adsorption and mobility of the herbicide linuron (3-3, 4-dichlorophenyl-1-methoxy
      1-methylurea) in 35 irrigated soils with organic matter (OM) contents in the 0.43
      2.59% range and in four natural soils with OM contents in the 4.16-11.69% range
      were studied using the batch equilibration technique. The adsorption isotherms
      were found to conform to the Freundlich adsorption equation. The Freundlich
      constant, K, and the distribution coefficient, K(d), were seen to be highly
      significantly correlated (p < 0.001) with the OM content when all soils or only
      those with an OM content above 2% were considered. There was also a significant
      correlation of K and K(d) with the OM content (p < 0.05) and of K(d) with the
      clay and silt plus clay contents (p < 0.1) when the soils with a OM content below
      2% were considered. On the basis of the R(f)() values obtained by soil TLC, the
      pesticide was found to be slightly mobile in 77% and moderately mobile in 23% of
      the soils studied. The results of the leaching of linuron in soil columns
      unmodified and modified with two organic agricultural amendments, a city refuse
      compost, and two surfactants (one of them cationic and the other anionic)
      revealed that the leaching rate and the mass transfer of the herbicide to water
      were affected, increasing or decreasing according to the characteristics of the
      amendments and the doses added. These results also point to the usefulness of
      selected organic materials and surfactants in the development of physicochemical
      methods for preventing the pollution of soils, sediments and aquifers by
      hydrophobic pesticides.

PMID- 10898660
TI  - Degradation behavior of soy protein-wheat gluten films in simulated soil
      conditions.
AB  - Films containing soy protein and wheat gluten were exposed to simulated farmland
      soil mix over a period of 30 days and monitored for degradation. The simulated
      farmland soil mix (topsoil/sand/Sunshine compost/vermiculite, 59:6:25:10, wt %)
      was mixed and stored at ambient humidity (48-55%) and temperature (20-24 degrees
      C); the soil mix was constantly maintained at 15% moisture by weight. Research
      focused on evaluating the effectiveness of gluten and cysteine additions on
      biodegradable behavior in the simulated farmland soil conditions. The four types
      of films, soy protein (S:G 1:0); soy protein with cysteine addition (S:G 1:0 +
      CYS); soy protein-wheat gluten (S:G 4:1); and soy protein-wheat gluten with
      cysteine addition (S:G 4:1 + CYS), were prepared at pH 7. 0 for degradation
      studies. Soy protein-gluten film rapidly degraded with 50% weight loss in about
      10 days and with up to 95% weight loss in 30 days. Tensile strength and
      elongation of all soy protein-gluten films significantly decreased in 3 days.
      However, cysteine addition delayed the degradation rate of soy protein-gluten
      films. Soy protein-wheat gluten film disintegrated after 20 days in the simulated
      farmland soil environment. These results suggest that wheat gluten and cysteine
      addition to soy protein-based films could delay degradation rates due to their
      high disulfide contents.

PMID- 10898661
TI  - Biodegradable films from isolate of sunflower (Helianthus annuus) proteins.
AB  - The film-forming potential of isolate of sunflower proteins (ISFP) was
      investigated. Homogeneous films were obtained by dissolution of ISFP in alkaline
      water (pH 12), addition of a plasticizer, casting, and drying. Maximum protein
      solubilization and unfolding led to films with the highest elasticity. The
      effects of five dissolving bases and five plasticizers on the mechanical
      properties were studied. The use of ionic bases (LiOH, NaOH) capable of
      interfering with the interproteic noncovalent bonds resulted in the greatest
      tensile strength (sigma(max)) and elongation at break (epsilon(max)) values (3.9
      MPa and 215-251%, respectively). Plasticizers conferred diverse tensile
      properties to the films: the use of 1,3-propanediol resulted in the highest
      sigma(max) (27.1 MPa), and glycerol resulted in the greatest epsilon(max) (251%).
      Different mechanical properties were obtained by using mixtures of these
      plasticizers.

PMID- 10898662
TI  - Comparison of the persistence of atrazine and metolachlor under field and
      laboratory conditions.
AB  - A study was carried out in a loamy soil to evaluate the degradation of atrazine
      and metolachlor under laboratory-controlled and field-variable conditions as a
      function of temperature and soil moisture content. In laboratory trials,
      metolachlor showed fast degradation, with half-lives from 100 to 5.7 days in a
      temperature range from 5 to 35 degrees C at 100% of field capacity, whereas in
      the same conditions the degradation rate of atrazine was relatively slow, with
      half-lives from 407 to 23 days. Modeling of laboratory degradation data to
      predict field persistence was carried out. Field persistence of atrazine and
      metolachlor was measured in the same soil during the corn growing seasons in
      1993, 1994, and 1996. In the three years the mean half-dissipation times for
      atrazine and metolachlor were 36 and 21 days, respectively. Calculations from
      model equations gave acceptable prediction of field dissipation of both
      herbicides. Limitations and perspectives of employed modelization procedure are
      discussed.

PMID- 10898663
TI  - Combined effect of sourdough lactic acid bacteria and additives on bread firmness
      and staling.
AB  - The effect of various sourdoughs and additives on bread firmness and staling was
      studied. Compared to the bread produced with Saccharomyces cerevisiae 141, the
      chemical acidification of dough fermented by S. cerevisiae 141 or the use of
      sourdoughs increased the volume of the breads. Only sourdough fermentation was
      effective in delaying starch retrogradation. The effect depended on the level of
      acidification and on the lactic acid bacteria strain. The effect of sourdough
      made of S. cerevisiae 141-Lactobacillus sanfranciscensis 57-Lactobacillus
      plantarum 13 was improved when fungal alpha-amylase or amylolytic strains such as
      L. amylovorus CNBL1008 or engineered L. sanfranciscensis CB1 Amy were added. When
      pentosans or pentosans, endoxylanase enzyme, and L. hilgardii S32 were added to
      the same sourdough, a greater delay of the bread firmness and staling was found.
      When pentosans were in part hydrolyzed by the endoxylanase enzyme, the bread also
      had the highest titratable acidity, due to the fermentation of pentoses by L.
      hilgardii S32. The addition of the bacterial protease to the sourdough increased
      the bread firmness and staling.

PMID- 10898664
TI  - Cloning and expression of an acidic pectin methylesterase from jelly fig (Ficus
      awkeotsang).
AB  - Pectin methylesterase (PME) is the key enzyme responsible for the gelation of
      jelly curd in the water extract of jelly fig (Ficus awkeotasang) achenes. The
      jelly fig PME extracted from achenes was isoelectrofocused at pH 2.5 and
      subjected to N-terminal amino acid sequencing. A cDNA fragment encoding the
      mature protein of this acidic PME was obtained by PCR cloning using a poly(T)
      primer and a degenerate primer designed according to the N-terminal sequence of
      the purified PME. The complete cDNA sequence of its precursor protein was further
      obtained by PCR using the same strategy. The PME clone was overexpressed in
      Escherichia coli, and its expressed protein was immunologically recognized as
      strongly as the original antigen using antibodies against purified PME.
      Fractionation analysis revealed that the overexpressed PME was predominantly
      present in the pellet and thus presumably formed insoluble inclusion bodies in E.
      coli cells.

PMID- 10898666
TI  - Influence of high-intensity ultrasound and heat treatment in continuous flow on
      fat, proteins, and native enzymes of milk

PMID- 10898665
TI  - Oxidation of spruce wood sawdust by MnO(2) plus oxalate: a biochemical
      investigation.
AB  - This paper reports the modification/degradation of lignin within spruce sawdust
      by manganese complexes formed by the association of MnO(2) and oxalate. The Mn
      oxidants formed are shown to modify both the chemical and physical properties of
      the wood cell wall. Scanning electron microscopy analysis of oxidized tracheids
      revealed a smoothing of the cell wall surface from the lumen side due to the
      removal of some material. Thioacidolysis analysis of the oxidized lignin showed
      reductions of up to 30% in the recovery of ether-linked guaiacyl monomers and up
      to 45% for the some dimers composing the polymer. The MnO(2)/oxalate system also
      slightly modified polysaccharides, corresponding to a 10% loss in weight of
      arabinose and glucose in the oxidized sample. However, no delignification
      occurred, according to the acid insoluble lignin content of spruce. Oxalic acid
      at pH 2.5 did not induce detectable changes in the chemical structures of the
      lignin or of the polysaccharides.

PMID- 10898667
TI  - Impact of standard vaccination of health care workers with hepatitis B vaccine on
      reducing the occupational risk of infection.

PMID- 10898668
TI  - Impact of antimicrobial agents and chemotherapy from 1972 to 1998.

PMID- 10898669
TI  - In vitro and in vivo activities of SCH 56592 (posaconazole), a new triazole
      antifungal agent, against Aspergillus and Candida.
AB  - SCH 56592 (posaconazole), a new triazole antifungal agent, was tested in vitro,
      and its activity was compared to that of itraconazole against 39 Aspergillus
      strains and to that of fluconazole against 275 Candida and 9 Cryptococcus
      strains. The SCH 56592 MICs for Aspergillus ranged from </=0.002 to 0.5
      microg/ml, and those of itraconazole ranged from </=0.008 to 1 microg/ml. The SCH
      56592 MICs for Candida and Cryptococcus strains ranged from </=0. 004 to 16
      microg/ml, and those of fluconazole ranged from </=0.062 to >64 microg/ml. SCH
      56592 showed excellent activity against Aspergillus fumigatus and Aspergillus
      flavus in a pulmonary mouse infection model. When administered therapeutically,
      the 50% protective doses (PD(50)s) of SCH 56592 ranged from 3.6 to 29.9 mg/kg of
      body weight, while the PD(50)s of SCH 56592 administered prophylactically ranged
      from 0.9 to 9.0 mg/kg; itraconazole administered prophylactically was ineffective
      (PD(50)s, >75 mg/kg). SCH 56592 was also very efficacious against fluconazole
      susceptible, -susceptible dose-dependent, or -resistant Candida albicans strains
      in immunocompetent or immunocompromised mouse models of systemic infection. The
      PD(50)s of SCH 56592 administered therapeutically ranged from 0.04 to 15.6 mg/kg,
      while the PD(50)s of SCH 56592 administered prophylactically ranged from 1.5 to
      19.4 mg/kg. SCH 56592 has excellent potential for therapy against serious
      Aspergillus or Candida infections.

PMID- 10898670
TI  - Amino acid substitutions in a variant of IMP-1 metallo-beta-lactamase.
AB  - In the course of surveying for the carbapenem-hydrolyzing metallo-beta-lactamase
      gene bla(IMP) in pathogenic bacteria by the PCR method, we detected a gene
      encoding a variant metallo-beta-lactamase, designated IMP-3, which differed from
      IMP-1 by having low hydrolyzing activity for penicillins and carbapenems. PCR
      product direct sequencing of a 2.2-kb segment revealed that the gene bla(IMP-3)
      was located on a cassette inserted within a class I integron in the pMS390
      plasmid. The 741-bp nucleotide sequence of bla(IMP-3) was identical to that of
      bla(IMP-1), except for seven base substitutions. Among these were two, at
      nucleotide positions 314 and 640, which caused amino acid alterations. Hybrid bla
      genes were constructed from bla(IMP-3) and bla(IMP-1) by recombinant DNA
      techniques, and beta-lactamases encoded by these genes were compared with those
      of the parents IMP-3 and IMP-1 under the same experimental conditions. The
      kinetic parameters indicated that the inefficient hydrolysis of benzylpenicillin,
      ampicillin, imipenem, and ceftazidime by IMP-3 was due to the substitution of
      glycine for serine at amino acid residue 196 in the mature enzyme. This
      alteration corresponded to the presence of guanine instead of an adenine at
      nucleotide position 640 of the bla(IMP-3) gene. This indicated that extension of
      the substrate profile in the metallo-beta-lactamase IMP-1 compared to IMP-3 is
      the result of a one-step single-base mutation, suggesting that the gene bla(IMP
      3) is an ancestor of bla(IMP-1).

PMID- 10898671
TI  - Monotherapy with a broad-spectrum beta-lactam is as effective as its combination
      with an aminoglycoside in treatment of severe generalized peritonitis: a
      multicenter randomized controlled trial. The Severe Generalized Peritonitis Study
      Group.
AB  - In a randomized trial conducted in 35 centers, we compared the clinical efficacy
      and safety of piperacillin plus tazobactam (TAZ) alone (monotherapy [MT]) versus
      those of TAZ combined with amikacin (AMK) (combined therapy [CT]) for the
      treatment of severe generalized peritonitis (SGP). Primary analysis consisted of
      blind assessment by an independent committee of the failure rate 30 days after
      the end of treatment in the modified intent-to-treat (ITT) analysis (mITT)
      population. Of the 241 patients with suspected SGP randomized into the study, 227
      were eligible for ITT analysis, including 204 (99 in the MT group and 105 in the
      CT group) with confirmed SGP (mITT population). A total of 159 patients were
      eligible for per-protocol (PP) analysis. The clinical failure rates were
      equivalent in the mITT and PP populations (MT versus CT): 56 versus 52%, (odds
      ratio [OR] 0.87, 90% confidence interval [CI] = 0. 6 to 1.27) for mITT and 49
      versus 49% (OR = 1.03, 90% CI = 0.67 to 1. 59) for PP analysis. Mortality rates
      (ITT population, 19%; PP population, 21%) and overall adverse event rates (ITT
      population, 55%; PP population, 54%) were also similar. Six patients (three in MT
      group and three in the CT group) developed acute renal failure. In conclusion,
      the addition of AMK to TAZ does not seem to be necessary for the treatment of
      SGP, even after adjustment for the simplified acute physiology score (SAPS II)
      and type of SGP.

PMID- 10898672
TI  - beta-lactamases in Shigella flexneri isolates from Hong Kong and Shanghai and a
      novel OXA-1-like beta-lactamase, OXA-30.
AB  - Ninety-one ampicillin-resistant Shigella flexneri strains from Hong Kong and
      Shanghai were studied for production of beta-lactamases. TEM-1-like and OXA-1
      like enzymes were identified in 21 and 79% of the strains, respectively, by
      isoelectric focusing (IEF). No difference in the pattern of beta-lactamase
      production was found between strains from Hong Kong and Shanghai. Four ribotypes
      were detected. Over 88% of OXA-producing strains had the same ribotype. All TEM-1
      like strains harbored a plasmid which hybridized positively with the bla(TEM)
      probe. Total DNA from OXA-1-like strains failed to hybridize or only hybridized
      weakly with an OXA probe. The OXA resistance was not transferable. OXA-1-like
      enzymes exhibited substrate and inhibition profiles similar to that of OXA-1 and
      were shown to have a pI of 7.3 by further IEF using a narrow-range ampholine gel.
      The gene encoding the OXA-1-like enzyme from one isolate (CH-07) was cloned,
      sequenced, and found to differ from bla(OXA-1) at codon 131 (AGA-->GGA; Arg to
      Gly), resulting in the novel designation OXA-30. The predominance of OXA-type
      enzymes in ampicillin-resistant S. flexneri suggests host preference for specific
      beta-lactamases.

PMID- 10898674
TI  - A population pharmacokinetic analysis of the penetration of the prostate by
      levofloxacin.
AB  - Prostatitis has remained a pathological entity that is difficult to treat. Part
      of the difficulty revolves about the putative offending pathogens. For acute
      prostatitis, members of the Enterobacteriaceae, particularly Escherichia coli,
      play a central role, while intracellular pathogens such as Chlamydia are more
      frequently seen in chronic prostatitis. Consequently, a drug needs to be able to
      penetrate to this specialized site in both the acute and chronic infection forms
      of the disease and also have potent activity against the most common causative
      pathogens, both intracellular and extracellular. Levofloxacin has such an
      activity profile. We wished to document its ability to penetrate to the site of
      infection. Patients undergoing prostatectomies were administered 500 mg of
      levofloxacin orally every 24 h for 2 days prior to surgery, and then on the day
      of surgery, 500 mg was administered as an hour-long, constant-rate intravenous
      (i.v.) infusion. A set of blood samples was obtained as guided by stochastic
      optimal design theory. Prostate biopsy times were determined by randomizing
      subjects into one of four groups, based on the interval after the i.v. dose. All
      plasma and prostate drug concentrations were comodeled by a population modeling
      program, BigNPEM, implemented on the Cray T3E Supercomputer housed at the
      Supercomputer Center at the University of California at San Diego. Penetration
      was determined as the ratio of the area under the concentration-time curve (AUC)
      of levofloxacin in the prostate to the plasma levofloxacin AUC. When calculated
      from the mean population parameters, this penetration ratio was 2.96. We also
      performed a 1,000-subject Monte Carlo simulation from the mean parameter vector
      and covariance matrix. The mean penetration ratio here was 4.14 with a 95%
      confidence interval of 0.20 to 19.6. Over 70% of the population had a penetration
      ratio in excess of 1.0. Levofloxacin adequately penetrates a noninflamed prostate
      and should be evaluated for the therapy of prostatitis.

PMID- 10898675
TI  - Population pharmacokinetics and pharmacodynamic modeling of abacavir (1592U89)
      from a dose-ranging, double-blind, randomized monotherapy trial with human
      immunodeficiency virus-infected subjects.
AB  - Abacavir (formerly 1592U89) is a carbocyclic nucleoside analog with potent anti
      human immunodeficiency virus (anti-HIV) activity when administered alone or in
      combination with other antiretroviral agents. The population pharmacokinetics and
      pharmacodynamics of abacavir were investigated in 41 HIV type 1 (HIV-1)-infected,
      antiretroviral naive adults with baseline CD4(+) cell counts of >/=100/mm(3) and
      plasma HIV-1 RNA levels of >30,000 copies/ml. Data for analysis were obtained
      from patients who received randomized, blinded monotherapy with abacavir at 100,
      300, or 600 mg twice-daily (BID) for up to 12 weeks. Plasma abacavir
      concentrations from sparse sampling were analyzed by standard population
      pharmacokinetic methods, and the effects of dose, combination therapy, gender,
      weight, and age on parameter estimates were investigated. Bayesian
      pharmacokinetic parameter estimates were calculated to determine the peak
      concentration of abacavir in plasma (C(max)) and the area under the concentration
      time curve from time zero to infinity (AUC(0-infinity)) for individual subjects.
      The pharmacokinetics of abacavir were dose proportional over the 100- to 600-mg
      dose range and were unaffected by any covariates. No significant correlations
      were observed between the incidence of the five most common adverse events
      (headache, nausea, diarrhea, vomiting, and malaise or fatigue) and AUC(0
      infinity). A significant correlation was observed between C(max) and nausea by
      categorical analysis (P = 0.019), but this was of borderline significance by
      logistic regression (odds ratio, 1.45; 95% confidence interval, 0.95 to 2.32).
      The log(10) time-averaged AUC(0-infinity) minus baseline (AAUCMB) values for HIV
      1 RNA and CD4(+) cell count correlated significantly with C(max) and AUC(0
      infinity), but with better model fits for AUC(0-infinity). The increase in AAUCMB
      values for CD4(+) cell count plateaued early for drug exposures that were
      associated with little change in AAUCMB values for plasma HIV-1 RNA. There was
      less than a 0.4 log(10) difference over 12 weeks in the HIV-1 RNA levels with the
      doubling of the abacavir AUC(0-infinity) from 300 to 600 mg BID dosing. In
      conclusion, pharmacodynamic modeling supports the selection of abacavir 300 mg
      twice-daily dosing.

PMID- 10898673
TI  - Characterization of a fish antimicrobial peptide: gene expression, subcellular
      localization, and spectrum of activity.
AB  - Antimicrobial peptides are proposed to act as the first line of mucosal host
      defense by exerting broad-spectrum microbicidal activity against pathogenic
      microbes. Pleurocidin, a new 25-residue linear antimicrobial peptide, was
      recently isolated from the skin secretions of winter flounder (Pleuronectes
      americanus). The present study identifies the cDNA and gene encoding pleurocidin.
      The pleurocidin gene comprises four exons. Its upstream region demonstrates
      consensus binding sequences for transcription factors found in host defense genes
      in mammals, including sequences identical to the NF-IL6 and alpha and gamma
      interferon response elements. Pleurocidin is predicted to exist as a 68-residue
      prepropeptide that undergoes proteolytic cleavage of its amino-terminal signal
      and carboxy-terminal anionic propiece to form the active, mature peptide.
      Transmission electron microscopy localized pleurocidin to the mucin granules of
      skin and intestinal goblet cells. Significant synergy was shown to occur between
      pleurocidin and D-cycloserine targeting Mycobacterium smegmatis. Pleurocidin was
      functionally active at physiologic concentrations of magnesium and calcium;
      however, high concentrations of these divalent cations ablated pleurocidin's
      activity against a standard test strain, Escherichia coli D31. Pleurocidin was
      tested against bacterial and fungal clinical isolates and showed broad-spectrum
      antimicrobial activity. Together, these data support the hypothesis that
      pleurocidin participates in innate mucosal immunity, and it may prove to be a
      beneficial therapeutic agent.

PMID- 10898676
TI  - Multiple-dose pharmacokinetics and pharmacodynamics of abacavir alone and in
      combination with zidovudine in human immunodeficiency virus-infected adults.
AB  - Abacavir (1592U89) is a nucleoside reverse transcriptase inhibitor with potent
      activity against human immunodeficiency virus type 1 (HIV-1) when used alone or
      in combination with other antiretroviral agents. The present study was conducted
      to determine the multiple-dose pharmacokinetics and pharmacodynamics of abacavir
      in HIV-1-infected subjects following oral administration of daily doses that
      ranged from 600 to 1,800 mg, with and without zidovudine. Seventy-nine subjects
      received abacavir monotherapy for 4 weeks (200, 400, or 600 mg every 8 hours
      [TID] and 300 mg every 12 h [BID]) and thereafter received either zidovudine (200
      mg TID or 300 mg BID) or matching placebo with abacavir for 8 additional weeks.
      Pharmacokinetic parameters were calculated for abacavir after administration of
      the first dose and at week 4 and for abacavir, zidovudine, and its glucuronide
      metabolite at week 12. The concentrations of abacavir in cerebrospinal fluid were
      determined in a subset of subjects. Steady-state plasma abacavir concentrations
      were achieved by week 4 of monotherapy and persisted to week 12. At steady state,
      abacavir pharmacokinetic parameters (area under the plasma concentration-time
      curve for a dosing interval [AUC(tau)] and peak concentration [C(max)]) were
      generally proportional to dose over the range of a 600- to 1,200-mg total daily
      dose. Coadministration of zidovudine with abacavir produced a small and
      inconsistent effect on abacavir pharmacokinetic parameters across the different
      doses. At the clinical abacavir dose (300 mg BID) zidovudine coadministration had
      no effect on the abacavir AUC(tau), which is most closely associated with
      efficacy. Zidovudine pharmacokinetics appeared to be unaffected by abacavir.
      Statistically significant but weak relationships were found for the change in the
      log(10) HIV-1 RNA load from the baseline to week 4 versus total daily AUC(tau)
      and C(tau) (P < 0.05). The incidence of nausea was significantly associated with
      total daily AUC(tau) and C(max). In conclusion, abacavir has predictable
      pharmacokinetic characteristics following the administration of multiple doses.

PMID- 10898677
TI  - Dose-dependent pharmacokinetics of amphotericin B lipid complex in rabbits.
AB  - Amphotericin B lipid complex (ABLC) was recently approved by the Food and Drug
      Administration for treatment of patients with invasive fungal infections who are
      intolerant of or refractory to conventional amphotericin B therapy. Little is
      known, however, about the pharmacokinetics of this new antifungal compound. We
      therefore investigated the pharmacokinetics of ABLC in comparison with those of
      conventional desoxycholate amphotericin B (DAmB) in rabbits. The pharmacokinetics
      of DAmB in a rabbit model were similar to those previously reported in humans.
      The pharmacokinetics of ABLC differed substantially from those of DAmB. Plasma
      amphotericin B levels following ABLC administration were 10 times lower than
      those following administration of an equal dosage of DAmB. The levels of ABLC in
      whole blood were approximately 40 times greater than those in plasma. The ABLC
      model differed from the DAmB model by (i) a dose- and time-dependent uptake and
      return between the plasma compartment and apparent cellular components of the
      blood-sediment compartment and (ii) time-dependent tissue uptake and return to
      plasma from serially connected compartments. Following infusion of ABLC, there
      was a nonlinear uptake into the apparent cellular components of the blood
      sediment compartment. This uptake was related to the reciprocal of the integral
      of the total amount of drug infused (i.e., the more drug infused the greater the
      fractional uptake between 0.5 and 5 mg/kg of body weight for ABLC). The transfer
      of drug from plasma to the cellular components of the blood-sediment compartment
      resulted in initial uptake followed by rapid redistribution back to the plasma.
      The study describes a detailed model of the pharmacokinetics of ABLC and
      characterizes a potential role of the cellular components of the blood-sediment
      compartment in the distribution of this new antifungal compound in tissue.

PMID- 10898678
TI  - Bactericidal activity of gentamicin against Enterococcus faecalis in vitro and in
      vivo.
AB  - The activity of gentamicin at various concentrations against two strains of
      Enterococcus faecalis was investigated in vitro and in a rabbit model of aortic
      endocarditis. In vitro, gentamicin at 0.5 to 4 times the MIC failed to reduce the
      number of bacteria at 24 h. Rabbit or human serum dramatically increased
      gentamicin activity, leading to a >/=3-log(10) CFU/ml decrease in bacterial
      counts when the drug concentration exceeded the MIC. Susceptibility testing in
      the presence of serum was predictive of in vivo activity, since gentamicin alone
      significantly reduced the number of surviving bacteria in the vegetations if the
      peak-to-MIC ratio was greater than 1. However, gentamicin selected resistant
      mutants in rabbits. The intrinsic activity of gentamicin should be taken into
      account in evaluation of combinations of gentamicin and cell wall-active agents
      against enterococci.

PMID- 10898679
TI  - Quantitation of Candida albicans ergosterol content improves the correlation
      between in vitro antifungal susceptibility test results and in vivo outcome after
      fluconazole treatment in a murine model of invasive candidiasis.
AB  - MIC end point determination for the most commonly prescribed azole antifungal
      drug, fluconazole, can be complicated by "trailing" growth of the organism during
      susceptibility testing by the National Committee for Clinical Laboratory
      Standards approved M27-A broth macrodilution method and its modified broth
      microdilution format. To address this problem, we previously developed the sterol
      quantitation method (SQM) for in vitro determination of fluconazole
      susceptibility, which measures cellular ergosterol content rather than growth
      inhibition after exposure to fluconazole. To determine if SQM MICs of fluconazole
      correlated better with in vivo outcome than M27-A MICs, we used a murine model of
      invasive candidiasis and analyzed the capacity of fluconazole to treat infections
      caused by C. albicans isolates which were trailers (M27-A MICs at 24 and 48 h,
      </=1.0 and >/=64 microg/ml, respectively; SQM MIC, </=1.0 microg/ml), as well as
      those which were fluconazole sensitive (M27-A and SQM MIC, </=1.0 microg/ml) and
      fluconazole resistant (M27-A MIC, >/=64 microg/ml; SQM MIC, 54 microg/ml).
      Compared with the untreated controls, fluconazole therapy increased the survival
      of mice infected with a sensitive isolate and both trailing isolates but did not
      increase the survival of mice infected with a resistant isolate. These results
      indicate that the SQM is more predictive of in vivo outcome than the M27-A method
      for isolates that give unclear MIC end points due to trailing growth in
      fluconazole.

PMID- 10898680
TI  - Antibacterial action of structurally diverse cationic peptides on gram-positive
      bacteria.
AB  - Antimicrobial cationic peptides are ubiquitous in nature and are thought to be a
      component of the first line of defense against infectious agents. It is widely
      believed that the killing mechanism of these peptides on bacteria involves an
      interaction with the cytoplasmic membrane. Cationic peptides from different
      structural classes were used in experiments with Staphylococcus aureus and other
      medically important gram-positive bacteria to gain insight into the mechanism of
      action. The membrane potential-sensitive fluorophore dipropylthiacarbocyanine was
      used to assess the interactions of selected antimicrobial peptides with the
      cytoplasmic membrane of S. aureus. Study of the kinetics of killing and membrane
      depolarization showed that, at early time points, membrane depolarization was
      incomplete, even when 90% or more of the bacteria had been killed. CP26, a 26
      amino-acid alpha-helical peptide with a high MIC against S. aureus, still had the
      ability to permeabilize the membrane. Cytoplasmic-membrane permeabilization was a
      widespread ability and an action that may be necessary for reaching an
      intracellular target but in itself did not appear to be the killing mechanism.
      Transmission electron microscopy of S. aureus and Staphylococcus epidermidis
      treated with CP29 (a 26-amino-acid alpha-helical peptide), CP11CN (a 13-amino
      acid, proline- and tryptophan-rich peptide), and Bac2A-NH(2) (a linearized
      version of the 12-amino-acid loop peptide bactenecin) showed variability in
      effects on bacterial structure. Mesosome-like structures were seen to develop in
      S. aureus, whereas cell wall effects and mesosomes were seen with S. epidermidis.
      Nuclear condensation and abherrent septation were occasionally seen in S.
      epidermidis. Our experiments indicated that these peptides vary in their
      mechanisms of action and that the mechanism of action likely does not solely
      involve cytoplasmic-membrane permeabilization.

PMID- 10898681
TI  - BMS-232632, a highly potent human immunodeficiency virus protease inhibitor that
      can be used in combination with other available antiretroviral agents.
AB  - BMS-232632 is an azapeptide human immunodeficiency virus type 1 (HIV-1) protease
      (Prt) inhibitor that exhibits potent anti-HIV activity with a 50% effective
      concentration (EC(50)) of 2.6 to 5.3 nM and an EC(90) of 9 to 15 nM in cell
      culture. Proof-of-principle studies indicate that BMS-232632 blocks the cleavage
      of viral precursor proteins in HIV-infected cells, proving that it functions as
      an HIV Prt inhibitor. Comparative studies showed that BMS-232632 is generally
      more potent than the five currently approved HIV-1 Prt inhibitors. Furthermore,
      BMS-232632 is highly selective for HIV-1 Prt and exhibits cytotoxicity only at
      concentrations 6,500- to 23, 000-fold higher than that required for anti-HIV
      activity. To assess the potential of this inhibitor when used in combination with
      other antiretrovirals, BMS-232632 was evaluated for anti-HIV activity in two-drug
      combination studies. Combinations of BMS-232632 with either stavudine,
      didanosine, lamivudine, zidovudine, nelfinavir, indinavir, ritonavir, saquinavir,
      or amprenavir in HIV-infected peripheral blood mononuclear cells yielded additive
      to moderately synergistic antiviral effects. Importantly, combinations of drug
      pairs did not result in antagonistic anti-HIV activity or enhanced cytotoxic
      effects at the highest concentrations used for antiviral evaluation. Our results
      suggest that BMS-232632 may be an effective HIV-1 inhibitor that may be utilized
      in a variety of different drug combinations.

PMID- 10898682
TI  - Mutations in Plasmodium falciparum cytochrome b that are associated with
      atovaquone resistance are located at a putative drug-binding site.
AB  - Atovaquone is the major active component of the new antimalarial drug Malarone.
      Considerable evidence suggests that malaria parasites become resistant to
      atovaquone quickly if atovaquone is used as a sole agent. The mechanism by which
      the parasite develops resistance to atovaquone is not yet fully understood.
      Atovaquone has been shown to inhibit the cytochrome bc(1) (CYT bc(1)) complex of
      the electron transport chain of malaria parasites. Here we report point mutations
      in Plasmodium falciparum CYT b that are associated with atovaquone resistance.
      Single or double amino acid mutations were detected from parasites that
      originated from a cloned line and survived various concentrations of atovaquone
      in vitro. A single amino acid mutation was detected in parasites isolated from a
      recrudescent patient following atovaquone treatment. These mutations are
      associated with a 25- to 9,354-fold range reduction in parasite susceptibility to
      atovaquone. Molecular modeling showed that amino acid mutations associated with
      atovaquone resistance are clustered around a putative atovaquone-binding site.
      Mutations in these positions are consistent with a reduced binding affinity of
      atovaquone for malaria parasite CYT b.

PMID- 10898683
TI  - Prevalence and characteristics of multinucleoside-resistant human
      immunodeficiency virus type 1 among European patients receiving combinations of
      nucleoside analogues.
AB  - The prevalence and the genotypic and phenotypic characteristics of
      multinucleoside-resistant (MNR) human immunodeficiency virus type 1 (HIV-1)
      variants in Europe were investigated in a multicenter study that involved centers
      in nine European countries. Study samples (n = 363) collected between 1991 and
      1997 from patients exposed to two or more nucleoside analogue reverse
      transcriptase inhibitors (NRTIs) and 274 control samples from patients exposed to
      no or one NRTI were screened for two marker mutations of multinucleoside
      resistance (the Q151M mutation and a mutation with a 2-amino-acid insertion at
      codon 69, T69S-XX). Q151M was identified in six of the study samples (1. 6%), and
      T69S-XX was identified in two of the study samples (0.5%; both of them T69S-SS),
      but both patterns were absent among control samples. Non-NRTI (NNRTI)-related
      changes were observed in viral strains from two patients, which displayed the
      Q151M resistance pattern, although the patients were NNRTI naive. The patients
      whose isolates displayed multinucleoside resistance had received treatment with
      zidovudine and either didanosine, zalcitabine, or stavudine. Both resistance
      patterns conferred broad cross-resistance to NRTIs in vitro and a poor response
      to treatment in vivo. MNR HIV-1 is found only among multinucleoside-experienced
      patients. Its prevalence is low in Europe, but it should be closely monitored
      since it seriously limits treatment options.

PMID- 10898685
TI  - Antimycobacterial activities of novel levofloxacin analogues.
AB  - In order to investigate structure-activity relationships between
      antimycobacterial activities and basic substituents at the C-10 position of
      levofloxacin (LVFX), we synthesized a series of pyridobenzoxazine derivatives by
      replacement of the N-methylpiperazinyl group of LVFX with various basic
      substituents. A compound with a 3-aminopyrrolidinyl group had one-half the
      activity of LVFX against Mycobacterium avium, M. intracellulare, and M.
      tuberculosis. Mono- and dimethylation of the 3-amino moiety of the pyrrolidinyl
      group increased the activities against M. avium and M. intracellulare but not
      those against M. tuberculosis. On the other hand, dialkylation at the C-4
      position of the 3-aminopyrrolidinyl group enhanced the activities against M.
      avium, M. intracellulare, and M. tuberculosis. Thus, introduction of an N-alkyl
      or a C-alkyl group(s) into the 3-aminopyrrolidinyl group may contribute to an
      increase in potency against M. avium, M. intracellulare, and/or M. tuberculosis,
      probably through elevation of the lipophilicity. However, among the compounds
      synthesized, compound VII, which was a 2,8-diazabicyclo[4.3.0]nonanyl derivative
      with relatively low lipophilicity, showed the most potent activity against
      mycobacterial species: the activity was 4- to 32-fold more potent than that of
      LVFX and two to four times as potent as that of gatifloxacin. These results
      suggested that an increase in the lipophilicity of LVFX analogues in part
      contributed to enhancement of antimycobacterial activities but that lipophilicity
      of the compound was not a critical factor affecting the potency.

PMID- 10898686
TI  - Antimicrobial susceptibilities and clinical sources of Facklamia species.
AB  - Facklamia spp. are gram-positive cocci, arranged in short chains or diplos, and
      resemble viridans streptococci on 5% sheep blood agar. Eighteen strains
      representing four species of Facklamia were isolated from blood cultures, an
      abscess, bone, cerebrospinal fluid, gall bladder, vaginal swab, and one unknown
      source. Cultures were tested against 15 antimicrobial agents by using the broth
      microdilution MIC method. Reduced susceptibilities to the beta lactams,
      erythromycin, clindamycin, trimethoprim-sulfamethoxazole, and tetracycline were
      found. These results indicate that the susceptibilities of the Facklamia species
      are varied and that some strains have resistance patterns which may present
      difficulty in managing systemic infections in patients.

PMID- 10898684
TI  - Mutations in 23S rRNA and ribosomal protein L4 account for resistance in
      pneumococcal strains selected in vitro by macrolide passage.
AB  - The mechanisms responsible for macrolide resistance in Streptococcus pneumoniae
      mutants, selected from susceptible strains by serial passage in azithromycin,
      were investigated. These mutants were resistant to 14- and 15-membered
      macrolides, but resistance could not be explained by any clinically relevant
      resistance determinant [mef(A), erm(A), erm(B), erm(C), erm(TR), msr(A), mph(A),
      mph(B), mph(C), ere(A), ere(B)]. An investigation into the sequences of 23S rRNAs
      in the mutant and parental strains revealed individual changes of C2611A, C2611G,
      A2058G, and A2059G (Escherichia coli numbering) in four mutants. Mutations at
      these residues in domain V of 23S rRNA have been noted to confer erythromycin
      resistance in other species. Not all four 23S rRNA alleles have to contain the
      mutation to confer resistance. Some of the mutations also confer coresistance to
      streptogramin B (C2611A, C2611G, and A2058G), 16-membered macrolides (all
      changes), and clindamycin (A2058G and A2059G). Interestingly, none of these
      mutations confer high-level resistance to telithromycin (HMR-3647). Further, two
      of the mutants which had no changes in their 23S rRNA sequences had changes in a
      highly conserved stretch of amino acids ((63)KPWRQKGTGRAR(74)) in ribosomal
      protein L4. One mutant contained a single amino acid change (G69C), while the
      other mutant had a 6-base insert, resulting in two amino acids (S and Q) being
      inserted between amino acids Q67 and K68. To our knowledge, this is the first
      description of mutations in 23S rRNA genes or ribosomal proteins in macrolide
      resistant S. pneumoniae strains.

PMID- 10898687
TI  - Analysis of rdxA and involvement of additional genes encoding NAD(P)H flavin
      oxidoreductase (FrxA) and ferredoxin-like protein (FdxB) in metronidazole
      resistance of Helicobacter pylori.
AB  - Metronidazole (Mtz) is a critical ingredient of modern multidrug therapies for
      Helicobacter pylori infection. Mtz resistance reduces the effectiveness of these
      combinations. Although null mutations in a rdxA gene that encodes oxygen
      insensitive NAD(P)H nitroreductase was reported in Mtz-resistant H. pylori, an
      intact rdxA gene has also been reported in Mtz-resistant H. pylori, suggesting
      that additional Mtz resistance mechanisms exist in H. pylori. We explored the
      nature of Mtz resistance among 544 clinical H. pylori isolates to clarify the
      role of rdxA inactivation in Mtz resistance and to identify another gene(s)
      responsible for Mtz resistance in H. pylori. Mtz resistance was present in 33%
      (181 of 544) of the clinical isolates. There was marked heterogeneity of
      resistance, with Mtz MICs ranging from 8 to >/=256 microg/ml. rdxA inactivation
      resulted in Mtz MICs of up to 32 microg/ml for 6 Mtz-sensitive H. pylori strains
      and 128 microg/ml for one Mtz-sensitive strain. Single or dual (with rdxA)
      inactivation of genes that encode ferredoxin-like protein (designated fdxB) and
      NAD(P)H flavin oxidoreductase (frxA) also increased the MICs of Mtz for sensitive
      and resistant strains with low to moderate levels of Mtz resistance. fdxB
      inactivation resulted in a lower level of resistance than that from rdxA
      inactivation, whereas frxA inactivation resulted in MICs similar to those seen
      with rdxA inactivation. Further evidence for involvement of the frxA gene in Mtz
      resistance included the finding of a naturally inactivated frxA but an intact
      rdxA in an Mtz-resistant strain, complementation of Mtz sensitivity from an Mtz
      sensitive strain to an Mtz-resistant strain or vice versa by use of naturally
      inactivated or functional frxA genes, respectively, and transformation of an Mtz
      resistant Escherichia coli strain to an Mtz sensitive strain by a naturally
      functional frxA gene but not an inactivated frxA gene. These results are
      consistent with the hypothesis that null mutations in fdxB, frxA, or rdxA may be
      involved in Mtz resistance.

PMID- 10898688
TI  - A double-blind placebo-controlled crossover trial of intravenous magnesium
      sulfate for foscarnet-induced ionized hypocalcemia and hypomagnesemia in patients
      with AIDS and cytomegalovirus infection.
AB  - Foscarnet (trisodium phosphonoformate hexahydrate) is an antiviral agent used to
      treat cytomegalovirus disease in immunocompromised patients. One common side
      effect is acute ionized hypocalcemia and hypomagnesemia following intravenous
      administration. Foscarnet-induced ionized hypomagnesemia might contribute to
      ionized hypocalcemia by impairing excretion of preformed parathyroid hormone
      (PTH) or by producing target organ resistance. Prevention of ionized
      hypomagnesemia following foscarnet administration could blunt the development of
      ionized hypocalcemia. To determine whether intravenous magnesium ameliorates the
      decline in ionized calcium and/or magnesium following foscarnet infusions,
      MgSO(4) at doses of 1, 2, and 3 g was administered in a double-blind, placebo
      controlled, randomized, crossover trial to 12 patients with AIDS and
      cytomegalovirus disease. Overall, increasing doses of MgSO(4) reduced or
      eliminated foscarnet-induced acute ionized hypomagnesemia. Supplementation,
      however, had no discernible effect on foscarnet-induced ionized hypocalcemia
      despite significant increases in serum PTH levels. No dose-related, clinically
      significant adverse events were found, suggesting that intravenous
      supplementation with up to 3 g of MgSO(4) was safe in this chronically ill
      population. Since parenteral MgSO(4) did not alter foscarnet-induced ionized
      hypocalcemia or symptoms associated with foscarnet, routine intravenous
      supplementation for patients with normal serum magnesium levels is not
      recommended during treatment with foscarnet.

PMID- 10898689
TI  - Pharmacokinetics of single-dose oral stavudine in subjects with renal impairment
      and in subjects requiring hemodialysis.
AB  - Two open-label studies assessed the pharmacokinetics of single orally
      administered doses of 40 mg of stavudine in subjects with renal impairment. In
      one study (study I), 15 subjects with selected degrees of renal impairment, but
      not requiring hemodialysis, were stratified into three groups of five subjects
      each according to creatinine clearance (CL(CR)) normalized by body surface area
      (ml/min/1.73 m(2)): mild (CL(CR), 60 to 80), moderate (30 to 50), and severe
      (</=20) renal impairment. Five healthy subjects (CL(CR) >/= 90) were also
      enrolled. The stavudine area under the curve from 0 h to infinity (AUC(0
      infinity)) increased nonlinearly with declining renal function: 1,864, 2,215,
      3,609, and 5,928 ng. h/ml for normal renal function and for mild, moderate, and
      severe renal impairment, respectively (P = 0.0001 between renal impairment
      groups). The following stavudine dosage recommendations for renal impairment were
      proposed for subjects weighing >/=60 kg: CL(CR) of >50 ml/min/1.73 m(2), 40 mg
      every 12 h; CL(CR) of 21 to 50 ml/min/1. 73 m(2), 20 mg every 12 h; and CL(CR) of
      10 to 20 ml/min/1.73 m(2), 20 mg every 24 h. For subjects weighing <60 kg, the
      proposed doses were 30, 15, and 15 mg, respectively, with the same dosing
      intervals specified above. In a second study (study II), 12 subjects with end
      stage renal disease requiring hemodialysis three times a week were enrolled in a
      randomized, open-label crossover study (dialysis 2 h after dosing and lasting 4 h
      or dosing without dialysis). There were no statistically significant differences
      for AUC(0-infinity), AUC(2-6), time to maximum concentration of drug in serum,
      half-life, or apparent oral clearance when the two treatment dosage regimens were
      compared. As a result of study II, the recommended dosing rate for subjects
      requiring hemodialysis was the same as that proposed for those with severe renal
      impairment not requiring hemodialysis; however, dosing was recommended to follow
      hemodialysis and to occur at the same time each day.

PMID- 10898690
TI  - Saccharomicins, novel heptadecaglycoside antibiotics produced by Saccharothrix
      espanaensis: antibacterial and mechanistic activities.
AB  - Saccharomicins A and B, two new heptadecaglycoside antibiotics, were isolated
      from the fermentation broth of the rare actinomycete Saccharothrix espanaensis.
      They represent a novel class of bactericidal antibiotics that are active both in
      vitro and in vivo against bacteria and yeast (MICs: Staphylococcus aureus, <0.12
      to 0. 5; vancomycin-resistant enterococci, 0.25 to 16; gram-negative bacteria,
      0.25 to >128; and yeast, >128 microg/ml), including multiply resistant strains.
      Saccharomicins protected mice from lethal challenges by staphylococci
      (subcutaneous 50% effective dose range of 0.06 to 2.6 mg/kg of body weight,
      depending on the S. aureus strain). The 50% lethal dose by the subcutaneous route
      was 16 mg/kg. Mechanistic studies with Escherichia coli imp and Bacillus subtilis
      suggested complete, nonspecific inhibition of DNA, RNA, and protein biosynthesis
      within 10 min of drug treatment. Microscopic examination of drug-treated cells
      also suggested cell lysis. These data are consistent with a strong membrane
      disruptive activity. The antibacterial activities of the saccharomicins against
      gram-positive bacteria were unaffected by the presence of Ca(2+) or Mg(2+), but
      activity against gram-negative bacteria was substantially reduced.

PMID- 10898691
TI  - Selective targeting of topoisomerase IV and DNA gyrase in Staphylococcus aureus:
      different patterns of quinolone-induced inhibition of DNA synthesis.
AB  - The effect of quinolones on the inhibition of DNA synthesis in Staphylococcus
      aureus was examined by using single resistance mutations in parC or gyrA to
      distinguish action against gyrase or topoisomerase IV, respectively. Norfloxacin
      preferentially attacked topoisomerase IV and blocked DNA synthesis slowly, while
      nalidixic acid targeted gyrase and inhibited replication rapidly. Ciprofloxacin
      exhibited an intermediate response, consistent with both enzymes being targeted.
      The absence of RecA had little influence on target choice by this assay,
      indicating that differences in rebound (repair) DNA synthesis were not
      responsible for the results. At saturating drug concentrations, norfloxacin and a
      gyrA mutant were used to show that topoisomerase IV-norfloxacin-cleaved DNA
      complexes are distributed on the S. aureus chromosome at intervals of about 30
      kbp. If cleaved complexes block DNA replication, as indicated by previous work,
      such close spacing of topoisomerase-quinolone-DNA complexes should block
      replication rapidly (replication forks are likely to encounter a cleaved complex
      within a minute). Thus, the slow inhibition of DNA synthesis at growth-inhibitory
      concentrations suggests that a subset of more distantly distributed complexes is
      physiologically relevant for drug action and is unlikely to be located
      immediately in front of the DNA replication fork.

PMID- 10898692
TI  - Antimicrobial resistance and spread of class 1 integrons among Salmonella
      serotypes.
AB  - The resistance profiles, for 15 antimicrobial agents, of 333 Salmonella strains
      representing the most frequent nontyphoidal serotypes, isolated between 1989 and
      1998 in a Spanish region, and 9 reference strains were analyzed. All strains were
      susceptible to amikacin, ceftazidime, ciprofloxacin, and imipenem, and 31% were
      susceptible to all antimicrobials tested. The most frequent types of resistance
      were to sulfadiazine, tetracycline, streptomycin, spectinomycin, ampicillin, and
      chloramphenicol (ranging from 46 to 22%); 13% were resistant to these six drugs.
      This multidrug resistance pattern was found alone or together with other
      resistance types within serotypes Typhimurium (45%), Panama (23%), and Virchow
      (4%). Each isolate was also screened for the presence of class 1 integrons and
      selected resistance genes therein; seven variable regions which carried one
      (aadA1a, aadA2, or pse-1) or two (dfrA14-aadA1a, dfrA1-aadA1a, oxa1-aadA1a, or
      sat1-aadA1a) resistance genes were found in integrons.

PMID- 10898693
TI  - Effects of fluconazole and clarithromycin on rifabutin and 25-O
      desacetylrifabutin pharmacokinetics.
AB  - Ten human immunodeficiency virus-infected patients were given rifabutin in
      addition to fluconazole and clarithromycin. There was a 76% increase in the area
      under the concentration-time curve of rifabutin when either fluconazole or
      clarithromycin was given alone and a 152% increase when both drugs were given
      together with rifabutin. Patients should be monitored for adverse effects of
      rifabutin administered concomitantly with clarithromycin and/or fluconazole.

PMID- 10898694
TI  - Indinavir population pharmacokinetics in plasma and cerebrospinal fluid. The HIV
      Neurobehavioral Research Center Group.
AB  - Plasma and cerebrospinal fluid (CSF) indinavir concentrations were measured by
      high-performance liquid chromatography. The median concentration in plasma
      exceeded that in CSF 10-fold. The modeled CSF curve was flat at 155 nM, and the
      estimated ratio of the areas under the CSF and plasma concentration-time curves
      was 6%. We conclude that CSF indinavir concentrations are lower than levels in
      plasma but exceed the clinical 95% inhibitory concentration range.

PMID- 10898695
TI  - In vitro activities of gemifloxacin versus five quinolones and two macrolides
      against 271 Spanish isolates of Legionella pneumophila: influence of charcoal on
      susceptibility test results.
AB  - The MICs at which 90% of isolates are inhibited for gemifloxacin, trovafloxacin,
      and grepafloxacin were low (</=0.01 microg/ml) for 271 Legionella isolates when
      they were determined by the broth microdilution method but increased (>/=6
      dilutions) when they were determined by the agar dilution method. This was due to
      the charcoal in the agar dilution medium, as shown by the progressive decrease in
      the MICs when the charcoal concentrations decreased. As free drug is the active
      fraction, charcoal binding should be considered.

PMID- 10898696
TI  - Synergy between trovafloxacin and ceftriaxone against penicillin-resistant
      pneumococci in the rabbit meningitis model and in vitro.
AB  - The bactericidal activities of monotherapy with trovafloxacin (-0.37 +/- 0.15
      Delta log(10) CFU/ml. h), vancomycin (-0.32 +/- 0.12 Delta log(10) CFU/ml. h),
      and ceftriaxone (-0.36 +/- 0.19 Delta log(10) CFU/ml. h) for the treatment of
      experimental meningitis in rabbits due to a clinical penicillin-resistant
      pneumococcal strain (MIC, 4 mg/liter) were similar. The combination of
      ceftriaxone with trovafloxacin considerably improved the killing rates (-0.67 +/-
      0.16 Delta log(10) CFU/ml. h) and was slightly superior to ceftriaxone with
      vancomycin (killing rate, -0.53 +/- 0. 22 Delta log(10) CFU/ml. h), the regimen
      most commonly used in clinical practice. In vitro, synergy was demonstrated
      between ceftriaxone and trovafloxacin by the checkerboard method (fractional
      inhibitory concentration index, 0.5) and by time-killing assays over 8 h.

PMID- 10898697
TI  - Selection of naturally occurring extended-spectrum TEM beta-lactamase variants by
      fluctuating beta-lactam pressure.
AB  - Despite the large number of in vitro mutations that increase resistance to
      extended-spectrum cephalosporins in TEM-type beta-lactamases, only a small number
      occur in naturally occurring enzymes. In nature, and particularly in the
      hospital, bacteria that contain beta-lactamases encounter simultaneous or
      consecutive selective pressure with different beta-lactam molecules. All variants
      obtained by submitting an Escherichia coli strain that contains a bla(TEM-1) gene
      to fluctuating challenge with both ceftazidime and amoxicillin contained only
      mutations previously detected in naturally occurring beta-lactamases.
      Nevertheless, some variants obtained by ceftazidime challenge alone contained
      mutations never detected in naturally occurring TEM beta-lactamases, suggesting
      that extended-spectrum TEM variants in hospital isolates result from fluctuating
      selective pressure with several beta-lactams rather than selection with a single
      antibiotic.

PMID- 10898698
TI  - Susceptibility testing of Malassezia species using the urea broth microdilution
      method.
AB  - A urea broth microdilution method to assay the susceptibilities of seven
      Malassezia species was developed. This method indicated the same sensitivities as
      the agar plate dilution method for isolates of Malassezia furfur, M.
      pachydermatis, M. slooffiae, and M. sympodialis.

PMID- 10898699
TI  - Impact of n-6 polyunsaturated fatty acids on growth of multidrug-resistant
      Pseudomonas aeruginosa: interactions with amikacin and ceftazidime.
AB  - Twenty-six multidrug-resistant Pseudomonas aeruginosa isolates were exposed over
      time to 300 microg of gamma-linolenic acid or arachidonic acid per ml or to the
      combination of both acids at 150 microg/ml each with ceftazidime and amikacin
      with or without albumin to observe the in vitro interactions of the antibiotics.
      Antibiotics and albumin were applied at their levels found in serum. Synergy
      between acids and antibiotics was found against 13 isolates, and it was expressed
      after 5 h of growth in the presence of albumin. The results indicate that further
      application in experimental infection models is merited.

PMID- 10898700
TI  - In vitro reversion of amphotericin B resistance in Leishmania donovani by
      poloxamer 188.
AB  - A micellar formulation of amphotericin B (AmB) solubilized with poloxamer 188 was
      evaluated against an AmB Leishmania donovani-resistant line. A concave
      isobologram showed a synergistic effect of this association against
      promastigotes. This result was confirmed with amastigotes since the 50% effective
      concentration of the new formulation was 100 times less than that of the control
      AmB formulation.

PMID- 10898701
TI  - Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae
      isolates from pediatric patients in Singapore.
AB  - One hundred eighty Streptococcus pneumoniae strains isolated from children at a
      pediatric hospital in Singapore from 1997 to 1999 were serotyped and their
      antimicrobial susceptibility patterns were determined. Sixty-three percent of the
      isolates were resistant to penicillin. Significantly large numbers of the strains
      investigated were resistant to trimethoprim-sulfamethoxazole (87.8%),
      tetracycline (71.7%), erythromycin (67.8%), and chloramphenicol (40%). Penicillin
      and multidrug resistance was mostly associated with the frequently isolated S.
      pneumoniae isolates of serotypes (serotypes 19F, 23F, 6B, and 14). Isolates of
      serotype 19F, the serotype most commonly encountered in Singapore (41.1%), had
      the highest prevalence of penicillin (78.4%) and multidrug resistance (94.6%).
      Most of the invasive S. pneumoniae isolates (8 of 17; 47. 1%) were of serotype
      14.

PMID- 10898702
TI  - Fluoroquinolone resistance associated with target mutations and active efflux in
      oropharyngeal colonizing isolates of viridans group streptococci.
AB  - Oropharyngeal samples from 60 hospitalized patients (30 fluoroquinolone [FQ]
      treated and 30 non-FQ-treated patients) and 30 untreated nonhospitalized healthy
      control subjects yielded 20 isolates of viridans group streptococci with reduced
      susceptibility to FQ, mostly from the hospitalized patients. An efflux phenotype
      was commonly encountered, expressed either alone or with topoisomerase mutations.
      Interspecies transfer of the efflux phenotype was demonstrated via transformation
      of Streptococcus pneumoniae R6 with DNA from S. mitis and S. oralis.

PMID- 10898703
TI  - Biochemical-genetic characterization and distribution of OXA-22, a chromosomal
      and inducible class D beta-lactamase from Ralstonia (Pseudomonas) pickettii.
AB  - From genomic DNA of Ralstonia pickettii isolate PIC-1, a beta-lactamase gene was
      cloned that encodes the oxacillinase OXA-22. It differs from known oxacillinases,
      being most closely related to OXA-9 (38% amino acid identity). The hydrolytic
      spectrum of OXA-22 is limited mostly to benzylpenicillin, cloxacillin, and
      restricted-spectrum cephalosporins. OXA-22-like genes were identified as single
      chromosomal copies in five other R. pickettii clinical isolates. The expression
      of OXA-22-like beta-lactamases was inducible in R. pickettii.

PMID- 10898704
TI  - In vitro activity and fecal concentration of rifaximin after oral administration.
AB  - Rifaximin showed moderately high MICs (the MIC at which 90% of the isolates
      tested were inhibited = 50 microg/ml) for 145 bacterial enteropathogens from
      patients with traveler's diarrhea acquired in Mexico during the summers of 1997
      and 1998. Rifaximin concentrations in stool the day after oral administration
      (800 mg daily for 3 days) were high (average, 7,961 microg/g), proving the value
      of the drug.

PMID- 10898705
TI  - Mechanism of metronidazole resistance in Helicobacter pylori: comparison of the
      rdxA gene sequences in 30 strains.
AB  - The rdxA gene of 30 independently isolated Helicobacter pylori strains was
      sequenced. A comparison of the rdxA sequences revealed a higher percentage of
      amino acid substitutions in the corresponding protein than in other housekeeping
      genes. Out of 122 point mutations, 41 were missense and 4 were nonsense. A
      resistant strain with a nucleotide insertion in the rdxA sequence was also found.
      With the exception of the point mutations and the insertion generating a stop
      signal, no particular nucleotide mutation or amino acid substitution could be
      associated to metronidazole resistance. Moreover, phylogenetic analysis of the 30
      nucleotide sequences did not demonstrate specific clusters associated with the
      resistance phenotype.

PMID- 10898706
TI  - Comparative activities of ciprofloxacin, clinafloxacin, gatifloxacin,
      gemifloxacin, levofloxacin, moxifloxacin, and trovafloxacin against
      epidemiologically defined Acinetobacter baumannii strains.
AB  - In vitro activities of seven fluoroquinolones against 140 clinical Acinetobacter
      baumannii isolates representing 138 different strain types were determined. The
      rank order of activity was clinafloxacin > gatifloxacin > levofloxacin >
      trovafloxacin > gemifloxacin = moxifloxacin > ciprofloxacin. The 31 outbreak
      related A. baumannii strains were significantly more resistant than were 109
      sporadic strains.

PMID- 10898707
TI  - Regional differences in metronidazole resistance and increasing clarithromycin
      resistance among Helicobacter pylori isolates from Japan.
AB  - The patterns of antibiotic resistance in Helicobacter pylori were assessed in two
      different regions in Japan. Overall, prevalences of resistance to metronidazole
      and clarithromycin were 12.4 and 12.9%, respectively. While there was no
      difference in clarithromycin resistance, the prevalence of metronidazole
      resistance was significantly higher in Kyoto (23.8%) than in Sapporo (8.1%). From
      1996 to 1999, the prevalence of metronidazole resistance did not change but the
      prevalence of clarithromycin resistance doubled (from 9.1 to 18.7%).

PMID- 10898708
TI  - In vitro antimicrobial activities of novel anilinouracils which selectively
      inhibit DNA polymerase III of gram-positive bacteria.
AB  - The 6-anilinouracils are novel dGTP analogs that selectively inhibit the
      replication-specific DNA polymerase III of gram-positive eubacteria. Two specific
      derivatives, IMAU (6-[3'-iodo-4'-methylanilino]uracil) and EMAU (6-[3'-ethyl-4'
      methylanilino]uracil), were substituted with either a hydroxybutyl (HB) or a
      methoxybutyl (MB) group at their N3 positions to produce four agents: HB-EMAU, MB
      EMAU, HB-IMAU, and MB-IMAU. These four new agents inhibited Staphylococcus
      aureus, coagulase-negative staphylococci, Enterococcus faecalis, and Enterococcus
      faecium. Time-kill assays and broth dilution testing confirmed bactericidal
      activity. These anilinouracil derivatives represent a novel class of
      antimicrobials with promising activities against gram-positive bacteria that are
      resistant to currently available agents, validating replication-specific DNA
      polymerase III as a new target for antimicrobial development.

PMID- 10898709
TI  - In vitro activities of MK-826 (L-749,345) against 363 strains of anaerobic
      bacteria.
AB  - The activity of MK-826 was compared to the activities of cefoxitin, ceftriaxone,
      imipenem, and meropenem against 363 gram-negative and gram-positive anaerobes by
      using NCCLS procedures. At least 98% of the strains were susceptible to the
      carbapenems. All strains of Clostridium perfringens, Fusobacterium nucleatum,
      Peptostreptococcus, and Sutterella wadsworthensis were susceptible to all agents
      tested.

PMID- 10898710
TI  - In vitro activities of the glycylcycline GAR-936 against gram-positive bacteria.
AB  - The in vitro activities of GAR-936, the 9-t-butylglycylamido derivative of
      minocycline, were compared with those of doxycycline, minocycline, and
      tetracycline against 527 gram-positive clinical isolates. GAR-936 inhibited all
      strains, including those resistant to other tetracyclines, at concentrations of
      </=2 microg/ml, except two strains of JK diphtheroids for which the MIC was 4
      microg/ml.

PMID- 10898711
TI  - Analysis of organ physiology in transgenic mice.
AB  - The increasing availability of transgenic mouse models of gene deletion and human
      disease has mandated the development of creative approaches to characterize mouse
      phenotype. The mouse presents unique challenges to phenotype analysis because of
      its small size, habits, and inability to verbalize clinical symptoms. This review
      describes strategies to study mouse organ physiology, focusing on the
      cardiovascular, pulmonary, renal, gastrointestinal, and neurobehavioral systems.
      General concerns about evaluating mouse phenotype studies are discussed.
      Monitoring and anesthesia methods are reviewed, with emphasis on the feasibility
      and limitations of noninvasive and invasive procedures to monitor physiological
      parameters, do cannulations, and perform surgical procedures. Examples of
      phenotype studies are cited to demonstrate the practical applications and
      limitations of the measurement methods. The repertoire of phenotype analysis
      methods reviewed here should be useful to investigators involved in or
      contemplating the use of mouse models.

PMID- 10898712
TI  - Olfactory receptor neurons are complex odorant information processors. Focus on
      "excitation, inhibition, and suppression by odors in isolated toad and rat
      olfactory receptor neurons".

PMID- 10898713
TI  - H(2)O(2)-mediated permeability: role of MAPK and occludin.
AB  - H(2)O(2)-mediated elevation in endothelial solute permeability is associated with
      pathological events such as ischemia-reperfusion and inflammation. To understand
      how H(2)O(2) mediates increased permeability, we investigated the effects of
      H(2)O(2) administration on vascular endothelial barrier properties and tight
      junction organization and function. We report that H(2)O(2) exposure caused an
      increase in endothelial solute permeability in a time-dependent manner through
      extracellularly regulated kinase 1 and 2 (ERK1/ERK2) signal pathways. H(2)O(2)
      exposure caused the tight junctional protein occludin to be rearranged from
      endothelial cell-cell junctions. Occludin rearrangement involved redistribution
      of occludin on the cell surface and dissociation of occludin from ZO-1. Occludin
      also was heavily phosphorylated on serine residues upon H(2)O(2) administration.
      H(2)O(2) mediates changes in ERK1/ERK2 phosphorylation, increases endothelial
      solute permeability, and alters occludin localization and phosphorylation were
      all blocked by PD-98059, a specific mitogen-activated protein (MAP) or ERK kinase
      1 inhibitor. These data strongly suggest that H(2)O(2)-mediated increased
      endothelial solute permeability involves the loss of endothelial tight junction
      integrity through increased ERK1/ERK2 activation.

PMID- 10898714
TI  - Excitation, inhibition, and suppression by odors in isolated toad and rat
      olfactory receptor neurons.
AB  - Vertebrate olfactory receptor neurons (ORNs) exhibit odor-induced increases in
      action potential firing rate due to an excitatory cAMP-dependent current. Fish
      and amphibian ORNs also give inhibitory odor responses, manifested as decreases
      in firing rate, but the underlying mechanism is poorly understood. In the toad,
      an odor-induced Ca(2+)-activated K(+) current is responsible for the
      hyperpolarizing receptor potential that causes inhibition. In isolated ORNs, a
      third manner by which odors affect firing is suppression, a direct and
      nonspecific reduction of voltage-gated and transduction conductances. Here we
      show that in whole cell voltage-clamped toad ORNs, excitatory or inhibitory
      currents were not strictly associated to a particular odorant mixture.
      Occasionally, both odor effects, in addition to suppression, were concurrently
      observed in a cell. We report that rat ORNs also exhibit odor-induced inhibitory
      currents, due to the activation of a K(+) conductance closely resembling that in
      the toad, suggesting that this conductance is widely distributed among
      vertebrates. We propose that ORNs operate as complex integrator units in the
      olfactory epithelium, where the first events in the process of odor
      discrimination take place.

PMID- 10898716
TI  - Intracellular Ca(2+) stores in chemoreceptor cells of the rabbit carotid body:
      significance for chemoreception.
AB  - The notion that intracellular Ca(2+) (Ca(i)(2+)) stores play a significant role
      in the chemoreception process in chemoreceptor cells of the carotid body (CB)
      appears in the literature in a recurrent manner. However, the structural identity
      of the Ca(2+) stores and their real significance in the function of chemoreceptor
      cells are unknown. To assess the functional significance of Ca(i)(2+) stores in
      chemoreceptor cells, we have monitored 1) the release of catecholamines (CA) from
      the cells using an in vitro preparation of intact rabbit CB and 2) the
      intracellular Ca(2+) concentration ([Ca(2+)](i)) using isolated chemoreceptor
      cells; both parameters were measured in the absence or the presence of agents
      interfering with the storage of Ca(2+). We found that threshold [Ca(2+)](i) for
      high extracellular K(+) (K(e)(+)) to elicit a release response is approximately
      250 nM. Caffeine (10-40 mM), ryanodine (0.5 microM), thapsigargin (0.05-1
      microM), and cyclopiazonic acid (10 microM) did not alter the basal or the
      stimulus (hypoxia, high K(e)(+))-induced release of CA. The same agents produced
      Ca(i)(2+) transients of amplitude below secretory threshold; ryanodine (0.5
      microM), thapsigargin (1 microM), and cyclopiazonic acid (10 microM) did not
      alter the magnitude or time course of the Ca(i)(2+) responses elicited by high
      K(e)(+). Several potential activators of the phospholipase C system (bethanechol,
      ATP, and bradykinin), and thereby of inositol 1,4,5-trisphosphate receptors,
      produced minimal or no changes in [Ca(2+)](i) and did not affect the basal
      release of CA. It is concluded that, in the rabbit CB chemoreceptor cells,
      Ca(i)(2+) stores do not play a significant role in the instant-to-instant
      chemoreception process.

PMID- 10898715
TI  - PKA and arachidonic acid activation of human recombinant ClC-2 chloride channels.
AB  - An HEK-293 cell line stably expressing the human recombinant ClC-2 Cl(-) channel
      was used in patch-clamp studies to study its regulation. The relative
      permeability P(x)/P(Cl) calculated from reversal potentials was I(-) > Cl(-) =
      NO(3)(-) = SCN(-)>/=Br(-). The absolute permeability calculated from conductance
      ratios was Cl(-) = Br(-) = NO(3)(-) >/= SCN(-) > I(-). The channel was activated
      by cAMP-dependent protein kinase (PKA), reduced extracellular pH, oleic acid
      (C:18 cisDelta9), elaidic acid (C:18 transDelta9), arachidonic acid (AA; C:20
      cisDelta5,8,11,14), and by inhibitors of AA metabolism, 5,8,11,14
      eicosatetraynoic acid (ETYA; C:20 transDelta5,8,11,14), alpha-methyl-4-(2
      methylpropyl)benzeneacetic acid (ibuprofen), and 2-phenyl-1,2-benzisoselenazol-3
      [2H]-one (PZ51, ebselen). ClC-2 Cl(-) channels were activated by a combination of
      forskolin plus IBMX and were inhibited by the cell-permeant myristoylated PKA
      inhibitor (mPKI). Channel activation by reduction of bath pH was increased by PKA
      and prevented by mPKI. AA activation of the ClC-2 Cl(-) channel was not inhibited
      by mPKI or staurosporine and was therefore independent of PKA or protein kinase C
      activation.

PMID- 10898717
TI  - CFTR induces the expression of DRA along with Cl(-)/HCO(3)(-) exchange activity
      in tracheal epithelial cells.
AB  - Thickening of airway mucus and lung dysfunction in cystic fibrosis (CF) results,
      at least in part, from abnormal secretion of Cl(-) and HCO(3)(-) across the
      tracheal epithelium. The mechanism of the defect in HCO(3)(-) secretion is ill
      defined; however, a lack of apical Cl(-)/HCO(3)(-) exchange may exist in CF. To
      test this hypothesis, we examined the expression of Cl(-)/HCO(3)(-) exchangers in
      tracheal epithelial cells exhibiting physiological features prototypical of
      cystic fibrosis [CFT-1 cells, lacking a functional cystic fibrosis transmembrane
      conductance regulator (CFTR)] or normal trachea (CFT-1 cells transfected with
      functional wild-type CFTR, termed CFT-WT). Cells were grown on coverslips and
      were loaded with the pH-sensitive dye 2', 7'-bis(2-carboxyethyl)-5(6)
      carboxyfluorescein, and intracellular pH was monitored. Cl(-)/HCO(3)(-) exchange
      activity increased by approximately 300% in cells transfected with functional
      CFTR, with activities increasing from 0.034 pH/min in CFT-1 cells to 0.11 in CFT
      WT cells (P < 0.001, n = 8). This activity was significantly inhibited by DIDS.
      The mRNA expression of the ubiquitous basolateral AE-2 Cl(-)/HCO(3)(-) exchanger
      remained unchanged. However, mRNA encoding DRA, recently shown to be a Cl(
      )/HCO(3)(-) exchanger (Melvin JE, Park K, Richardson L, Schultheis PJ, and Shull
      GE. J Biol Chem 274: 22855-22861, 1999.) was abundantly expressed in cells
      expressing functional CFTR but not in cells that lacked CFTR or that expressed
      mutant CFTR. In conclusion, CFTR induces the mRNA expression of "downregulated in
      adenoma" (DRA) and, as a result, upregulates the apical Cl(-)/HCO(3)(-) exchanger
      activity in tracheal cells. We propose that the tracheal HCO(3)(-) secretion
      defect in patients with CF is partly due to the downregulation of the apical Cl(
      )/HCO(3)(-) exchange activity mediated by DRA.

PMID- 10898718
TI  - Insight into the mechanism by which metoclopramide improves immune functions
      after trauma-hemorrhage.
AB  - Although studies have shown that prolactin (Prl) and metoclopramide (Mcp)
      administration restores the depressed cell-mediated immune functions after
      hemorrhage, the underlying mechanism responsible for the immunostimulatory
      effects of Mcp remains unknown. We hypothesized that Mcp improves immune
      responses by upregulating the secretion of Prl. To test this hypothesis, male
      C3H/HeN mice were subjected to sham operation or laparotomy (i.e., soft tissue
      trauma) and hemorrhagic shock (Hem; 35 +/- 5 mmHg for 90 min) and then
      resuscitated. Plasma Prl levels were determined 30 min after Mcp (1 microgram/g
      body wt sc at end of Hem) or vehicle (Veh) treatment in sham and Hem mice. The
      results indicate that plasma Prl levels increased significantly in Mcp-treated
      mice (sham-Veh 249.9 +/- 5.3, Hem-Veh 229.9 +/- 7.6, Hem-Mcp 596.9 +/- 73.1
      ng/ml, one-way ANOVA, P < 0.05 vs. Veh). To determine whether Mcp produces its
      salutary effects directly or indirectly via increased Prl secretion, splenocyte
      proliferation and splenocyte interleukin (IL)-2 and IL-3 release from untreated
      sham or Hem mice were determined in the presence of increasing concentrations of
      mouse Prl or Mcp. The addition of Mcp had no effect on splenocyte immune
      functions in vitro. However, the addition of Prl restored the hemorrhage-induced
      depressed splenocyte proliferation as well as splenocyte IL-2 and IL-3 release in
      vitro in a dose-dependent manner. Thus the beneficial effects of Mcp on immune
      functions after Hem appear to be mediated by Prl. Because Mcp increases plasma
      levels of the immunoenhancing hormone Prl, this agent should be considered a
      useful adjunct for the treatment of immunodepression in trauma victims.

PMID- 10898719
TI  - The effect of rapamycin on single ENaC channel activity and phosphorylation in A6
      cells.
AB  - Rapamycin and FK-506 are immunosuppressive drugs that bind a ubiquitous
      immunophilin, FKBP12, but immunosuppressive mechanisms and side effects appear to
      be different. Rapamycin binds renal FKBP12 to change renal transport. We used
      cell-attached patch clamp to examine rapamycin's effect on Na(+) channels in A6
      cells. Channel NP(o) was 0.5 +/- 0.08 (n = 6) during the first 5 min but fell
      close to zero after 20 min. Application of 1 microM rapamycin reactivated Na(+)
      channels (NP(o) = 0.47 +/- 0.1; n=6), but 1 microM FK-506 did not. Also, GF
      109203X, a protein kinase C (PKC) inhibitor, mimicked the rapamycin-induced
      reactivation in a nonadditive manner. However, rapamycin did not reactivate Na(+)
      channels if cells were exposed to 1 microM FK-506 before rapamycin. In PKC
      assays, rapamycin was as effective as the PKC inhibitor; however, epithelial
      Na(+) channel (ENaC) phosphorylation was low under baseline conditions and was
      not altered by PKC inhibitors or activators. These results suggest that rapamycin
      activates Na(+) channels by binding FKBP12 and inhibiting PKC, and, in renal
      cells, despite binding the same immunophilin, rapamycin and FK-506 activate
      different intracellular signaling pathways.

PMID- 10898720
TI  - Sodium/calcium exchange in amphibian skeletal muscle fibers and isolated
      transverse tubules.
AB  - The Na(+)/Ca(2+) exchanger participates in Ca(2+) homeostasis in a variety of
      cells and has a key role in cardiac muscle physiology. We studied in this work
      the exchanger of amphibian skeletal muscle, using both isolated inside-out
      transverse tubule vesicles and single muscle fibers. In vesicles, increasing
      extravesicular (intracellular) Na(+) concentration cooperatively stimulated
      Ca(2+) efflux (reverse mode), with the Hill number equal to 2.8. In contrast to
      the stimulation of the cardiac exchanger, increasing extravesicular (cytoplasmic)
      Ca(2+) concentration ([Ca(2+)]) inhibited this reverse activity with an IC(50) of
      91 nM. Exchanger-mediated currents were measured at 15 degrees C in single fibers
      voltage clamped at -90 mV. Photolysis of a cytoplasmic caged Ca(2+) compound
      activated an inward current (forward mode) of 23 +/- 10 nA (n = 3), with an
      average current density of 0.6 muA/muF. External Na(+) withdrawal generated an
      outward current (reverse mode) with an average current density of 0.36 +/- 0.17
      muA/muF (n = 6) but produced a minimal increase in cytosolic [Ca(2+)]. These
      results suggest that, in skeletal muscle, the main function of the exchanger is
      to remove Ca(2+) from the cells after stimulation.

PMID- 10898721
TI  - Antithrombin reduces leukocyte adhesion during chronic endotoxemia by modulation
      of the cyclooxygenase pathway.
AB  - Antithrombin (AT) is known as the most important natural inhibitor of thrombin
      activity and has been shown to improve distinct clinical parameters during the
      course of septic (endotoxin)-induced multiple organ dysfunction. We hypothesized
      that AT acts by inhibiting leukocyte activation and microvascular injury via the
      promotion of endothelial release of PGI(2), and therefore, we studied the effects
      of AT on leukocyte/endothelial cell interaction and microvascular perfusion
      during endotoxemia. In a skinfold preparation of Syrian hamsters, severe
      endotoxemia was induced by repeated administration of endotoxin intravenously
      [lipopolysaccharide (LPS), Escherichia coli, 2 mg/kg] at 0 and 48 h. AT (250
      IU/kg) was administered intravenously at 0, 24, and 48 h (n = 6, AT group). In
      control animals (n = 5, control), LPS was given without AT supplementation. By
      intravital fluorescence microscopy, leukocyte-endothelial cell interaction and
      functional capillary density (FCD; measure of capillary perfusion) were analyzed
      during a 72-h period after the first LPS injection. AT significantly attenuated
      LPS-induced arteriolar and venular leukocyte adherence after both the first and
      the second LPS injection [P < 0.01, measures analysis of variance (MANOVA)]. In
      parallel, AT was effective in preventing LPS-induced depression of FCD after the
      first and the second LPS administration (P < 0.05, MANOVA). By pretreatment with
      the cyclooxygenase inhibitor indomethacin (n = 6), effects of AT on leukocyte
      adherence and FCD were found completely abolished. Thus our study indicates that
      AT exerts its beneficial effects in endotoxemia by reducing leukocyte-endothelial
      cell interaction and microvascular perfusion failure probably via liberation of
      prostacyclin from endothelial cells.

PMID- 10898722
TI  - Role of protein phosphatases in the activation of CFTR (ABCC7) by genistein and
      bromotetramisole.
AB  - Genistein and bromotetramisole (Br-t) strongly activate cystic fibrosis
      transmembrane conductance regulator (CFTR; ABCC7) chloride channels on Chinese
      hamster ovary cells and human airway epithelial cells. We have examined the
      possible role of phosphatases in stimulation by these drugs using patch-clamp and
      biochemical methods. Genistein inhibited the spontaneous rundown of channel
      activity that occurs after membrane patches are excised from cAMP-stimulated
      cells but had no effect on purified protein phosphatase type 1 (PP1), PP2A, PP2B,
      PP2C, or endogenous phosphatases when assayed as [(32)P]PO(4) release from
      prelabeled casein, recombinant GST-R domain fusion protein, or immunoprecipitated
      full-length CFTR. Br-t also slowed rundown of CFTR channels, but, in marked
      contrast to genistein, it did inhibit all four protein phosphatases tested. Half
      maximal inhibition of PP2A and PP2C was observed with 0.5 and 1.5 mM Br-t,
      respectively. Protein phosphatases were also sensitive to (+)-p-Br-t, a
      stereoisomer of Br-t that does not inhibit alkaline phosphatases. Br-t appeared
      to act exclusively through phosphatases since it did not affect CFTR channels in
      patches that had low apparent endogenous phosphatase activity (i.e., those
      lacking spontaneous rundown). We conclude that genistein and Br-t act through
      different mechanisms. Genistein stimulates CFTR without inhibiting phosphatases,
      whereas Br-t acts by inhibiting a membrane-associated protein phosphatase
      (probably PP2C) that presumably allows basal phosphorylation to accumulate.

PMID- 10898723
TI  - Sucrose-stimulated subsecond transient increase in cGMP level in rat intact
      circumvallate taste bud cells.
AB  - Initial sweet taste transduction is expected to occur in the subsecond time
      range. We demonstrate a rapid and transient (75-250 ms) increase of cGMP (but not
      cAMP) level in rat intact circumvallate taste cells after stimulation by sucrose.
      This rapid increase does not occur in nonsensory epithelial cells. Pretreatment
      with a nonspecific phosphodiesterase (PDE) inhibitor (IBMX), a specific cAMP-PDE4
      inhibitor (denbufylline), or an adenylyl cyclase activator (forskolin) all
      increased basal cAMP and abolished the sucrose-stimulated cGMP increase at 150
      ms. Pretreatment with a soluble guanylyl cyclase inhibitor (1H
      [1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one) reduced, whereas a specific cGMP-PDE
      inhibitor (zaprinast) abolished, the sucrose-stimulated cGMP increase. It is
      proposed that cGMP is involved in the initial stage of sugar taste transduction
      and that cGMP is more significant than cAMP at this stage. Activation of soluble
      guanylyl cyclase and inhibition of cGMP-PDE may be involved in the transient
      elevation of cGMP in response to sucrose stimulation. Moreover, it appears that
      cAMP level must remain low for sucrose to stimulate an increase in cGMP.

PMID- 10898724
TI  - Intracellular calcium events activated by ATP in murine colonic myocytes.
AB  - ATP is a candidate enteric inhibitory neurotransmitter in visceral smooth
      muscles. ATP hyperpolarizes visceral muscles via activation of small-conductance,
      Ca(2+)-activated K(+) (SK) channels. Coupling between ATP stimulation and SK
      channels may be mediated by localized Ca(2+) release. Isolated myocytes of the
      murine colon produced spontaneous, localized Ca(2+) release events. These events
      corresponded to spontaneous transient outward currents (STOCs) consisting of
      charybdotoxin (ChTX)-sensitive and -insensitive events. ChTX-insensitive STOCs
      were inhibited by apamin. Localized Ca(2+) transients were not blocked by
      ryanodine, but these events were reduced in magnitude and frequency by
      xestospongin C (Xe-C), a blocker of inositol 1,4,5-trisphosphate receptors. Thus
      we have termed the localized Ca(2+) events in colonic myocytes "Ca(2+) puffs. "
      The P(2Y) receptor agonist 2-methylthio-ATP (2-MeS-ATP) increased the intensity
      and frequency of Ca(2+) puffs. 2-MeS-ATP also increased STOCs in association with
      the increase in Ca(2+) puffs. Pyridoxal-phospate-6-azophenyl-2',4'-disculfonic
      acid tetrasodium, a P(2) receptor inhibitor, blocked responses to 2-MeS-ATP.
      Spontaneous Ca(2+) transients and the effects of 2-MeS-ATP on Ca(2+) puffs and
      STOCs were blocked by U-73122, an inhibitor of phospholipase C. Xe-C and
      ryanodine also blocked responses to 2-MeS-ATP, suggesting that, in addition to
      release from IP(3) receptor-operated stores, ryanodine receptors may be recruited
      during agonist stimulation to amplify release of Ca(2+). These data suggest that
      localized Ca(2+) release modulates Ca(2+)-dependent ionic conductances in the
      plasma membrane. Localized Ca(2+) release may contribute to the electrical
      responses resulting from purinergic stimulation.

PMID- 10898725
TI  - Osmotically relevant membrane signaling complex: association between HB-EGF,
      beta(1)-integrin, and CD9 in mTAL.
AB  - The integral membrane proteins cluster of differentiation-9 (CD9), beta(1)
      integrin, and heparin-binding epidermal growth factor-like (HB-EGF) exist in
      association in many cell lines and are linked to intracellular signaling
      mechanisms. Two of the proteins (CD9 and beta(1)-integrin) are induced by
      hypertonicity, suggesting that their related signaling processes may be relevant
      to osmotic stress. The validity of this hypothesis rests upon coexpression and
      physical association between these molecules in nephron segments that are
      normally exposed to high and variable ambient osmolality. In this work, we show
      that CD9 and beta(1)-integrin are induced in rat kidney medulla after
      dehydration. Immunohistochemistry and immunoprecipitation studies show that CD9,
      HB-EGF, and beta(1)-integrin are coexpressed and physically associated in
      medullary thick ascending limbs (mTAL), nephron segments that are normally
      exposed to high and variable extracellular osmolality. Our findings are
      consistent with the existence of a cluster of integral membrane proteins in mTAL
      that may initiate or modulate osmotically relevant signaling pathways.

PMID- 10898726
TI  - Biochemical and functional characterization of intercellular adhesion and gap
      junctions in fibroblasts.
AB  - Despite their significance in wound healing, little is known about the molecular
      determinants of cell-to-cell adhesion and gap junctional communication in
      fibroblasts. We characterized intercellular adherens junctions and gap junctions
      in human gingival fibroblasts (HGFs) using a novel model. Calcein-labeled donor
      cells in suspension were added onto an established, Texas red dextran (10 kDa)
      labeled acceptor cell monolayer. Cell-to-cell adhesion required Ca(2+) and was
      >30-fold stronger than cell-to-fibronectin adhesion at 15 min. Electron
      micrographs showed rapid formation of adherens junction-like structures at
      approximately 15 min that matured by approximately 2-3 h; distinct gap junctional
      complexes were evident by approximately 3 h. Immunoblotting showed that HGF
      expressed beta-catenin and that cadherins and connexin43 were recruited to the
      Triton-insoluble cytoskeletal fraction in confluent cultures. Confocal microscopy
      localized the same molecules to intercellular contacts of acceptor and donor
      cells. There was extensive calcein dye transfer in a cohort of Texas red dextran
      labeled cells, but this was almost completely abolished by the gap junction
      inhibitor beta-glycyrrhetinic acid and the connexin43 mimetic peptide GAP 27.
      This donor-acceptor cell model allows large numbers (>10(5)) of cells to form
      synchronous cell-to-cell contacts, thereby enabling the simultaneous functional
      and molecular studies of adherens junctions and gap junctions.

PMID- 10898727
TI  - Induction of apoptosis using sphingolipids activates a chloride current in
      Xenopus laevis oocytes.
AB  - The purpose of this study was to investigate whether the cell shrinkage that
      occurs during apoptosis could be explained by a change of the activity in ion
      transport pathways. We tested whether sphingolipids, which are potent pro
      apoptotic compounds, can activate ionic currents in Xenopus laevis oocytes.
      Apoptosis was characterized in our model by a decrease in cell volume, a loss of
      cell viability, and DNA cleavage. Oocytes were studied using voltage-clamp after
      injection with N,N-dimethyl-D-erythrosphingosine (DMS) or D-sphingosine (DS). DMS
      and DS activated a fast-activating, slowly inactivating, outwardly rectifying
      current, similar to I(Cl-swell), a swelling-induced chloride current. Lowering
      the extracellular chloride dramatically reduced the current, and the channel was
      more selective for thiocyanate and iodide (thiocyanate > iodide) than for
      chloride. The current was blocked by 5-nitro-2-(3-phenylpropylamino)-benzoic acid
      (NPPB) and lanthanum but not by niflumic acid. Oocytes injected with a
      pseudosubstrate inhibitor of protein kinase C (PKC), PKC-(19-31), exhibited the
      same current. DMS-activated current was abolished by preexposure with phorbol
      myristate acetate. Our results suggest that induction of apoptosis in X. laevis
      oocytes, using sphingolipids or PKC inhibitors, activates a current similar to
      swelling-induced chloride current previously described in oocytes.

PMID- 10898728
TI  - Interaction of D-600 with the transmembrane domain of the sarcoplasmic reticulum
      Ca(2+)-ATPase.
AB  - Experiments were performed to determine whether the organic Ca(2+) channel
      blocker D-600 (gallopamil), which penetrates into muscle cells, affects
      sarcoplasmic reticulum (SR) Ca(2+) uptake by directly inhibiting the light SR
      Ca(2+)-ATPase. We have previously shown that at 10 microM, D-600 inhibits LSR ATP
      dependent Ca(2+) uptake by 50% but has no effect on ATPase activity (21). These
      data suggest that the SR Ca(2+)-ATPase might be a potential target for D-600. The
      ATPase activity of the enzyme is associated with its hydrophilic cytoplasmic
      domain, whereas Ca(2+) binding and translocation are associated with the
      transmembrane domain (18). In the present experiments, we determined which of the
      two domains of the ATPase is affected by D-600. Thermal inactivation experiments
      using the SR Ca(2+)-ATPase demonstrated that D-600 decreased the thermal
      stability of Ca(2+) transport but had no effect on the stability of ATPase
      activity. In addition, D-600 at a concentration of 160 microM did not have any
      leaking effect of Ca(2+) on the Ca(2+)-loaded SR. Thermal denaturation profiles
      of SR membranes revealed that D-600 interacts directly with the transmembrane
      domain of the Ca(2+)-ATPase. No evidence for interaction with the nucleotide
      domain was obtained. We conclude that the Ca(2+) blocker D-600 inhibits the SR
      Ca(2+) pump specifically by interacting with the transmembrane Ca(2+)-binding
      domain of the Ca(2+)-ATPase.

PMID- 10898729
TI  - cAMP activates an ATP-permeable pathway in neonatal rat cardiac myocytes.
AB  - The molecular mechanisms associated with intracellular ATP release by the heart
      are largely unknown. In this study the luciferin-luciferase assay and patch-clamp
      techniques were used to characterize the pathways responsible for ATP release in
      neonatal rat cardiac myocytes (NRCM). Spontaneous ATP release by NRCM was
      significantly increased after cAMP stimulation under physiological conditions.
      cAMP stimulation also induced an anion-selective electrodiffusional pathway that
      elicited linear, diphenylamine-2-carboxylate (DPC)-inhibitable Cl(-) currents in
      either symmetrical MgCl(2) or NaCl. ATP, adenosine 5'-O-(3-thiotriphosphate), and
      the ATP derivatives ADP and AMP, permeated this pathway; however, GTP did not.
      The cAMP-induced ATP currents were inhibited by DPC and glibenclamide and by a
      monoclonal antibody raised against the R domain of the cystic fibrosis
      transmembrane conductance regulator (CFTR). The channel-like nature of the cAMP
      induced ATP-permeable pathway was also determined by assessing protein kinase A
      activated single channel Cl(-) and ATP currents in excised inside-out patches of
      NRCM. Single channel currents were inhibited by DPC and the anti-CFTR R domain
      antibody. Thus the data in this report demonstrate the presence of a cAMP
      inducible electrodiffusional ATP transport mechanism in NRCM. Based on the
      pharmacology, patch-clamping data, and luminometry studies, the data are most
      consistent with the role of a functional CFTR as the anion channel implicated in
      cAMP-activated ATP transport in NRCM.

PMID- 10898730
TI  - Contribution of intermediate filaments to cell stiffness, stiffening, and growth.
AB  - It has been shown previously that intermediate filament (IF) gels in vitro
      exhibit stiffening at high-applied stress, and it was suggested that this
      stiffening property of IFs might be important for maintaining cell integrity at
      large deformations (Janmey PA, Evtenever V, Traub P, and Schliwa M, J Cell Biol
      113: 155-160, 1991). In this study, the contribution of IFs to cell mechanical
      behavior was investigated by measuring cell stiffness in response to applied
      stress in adherent wild-type and vimentin-deficient fibroblasts using magnetic
      twisting cytometry. It was found that vimentin-deficient cells were less stiff
      and exhibited less stiffening than wild-type cells, except at the lowest applied
      stress (10 dyn/cm(2)) where the difference in the stiffness was not significant.
      Similar results were obtained from measurements on wild-type fibroblasts and
      endothelial cells after vimentin IFs were disrupted by acrylamide. If, however,
      cells were plated over an extended period of time (16 h), they exhibited a
      significantly greater stiffness before than after acrylamide, even at the lowest
      applied stress. A possible reason could be that the initially slack IFs became
      fully extended due to a high degree of cell spreading and thus contributed to the
      transmission of mechanical stress across the cell. Taken together, these findings
      were consistent with the notion that IFs play important roles in the mechanical
      properties of the cell during large deformation. The experimental data also
      showed that depleting or disrupting IFs reduced, but did not entirely abolish,
      cell stiffening. This residual stiffening might be attributed to the effect of
      geometrical realignment of cytoskeletal filaments in the direction of applied
      load. It was also found that vimentin-deficient cells exhibited a slower rate of
      proliferation and DNA synthesis than wild-type cells. This could be a direct
      consequence of the absence of the intracellular IFs that may be necessary for
      efficient mediation of mechanical signals within the cell. Taken together,
      results of this study suggest that IFs play important roles in the mechanical
      properties of cells and in cell growth.

PMID- 10898731
TI  - ROCK mediates thrombin's endothelial barrier dysfunction.
AB  - Thrombin-induced endothelial monolayer hyperpermeability is thought to result
      from increased F-actin stress fiber-related contractile tension, a process
      regulated by the small GTP-binding protein Rho. We tested whether this process
      was dependent on the Rho-associated protein kinase, ROCK, using a specific ROCK
      inhibitor, Y-27632. The effects of Y-27632 on thrombin-induced myosin light chain
      phosphorylation (MLCP) and tyrosine phosphorylation of p125 focal adhesion kinase
      (p125(FAK)) and paxillin were measured by Western blotting. F-actin organization
      and content were analyzed by digital imaging, and endothelial monolayer
      permeability was measured in bovine pulmonary artery endothelial cell (EC)
      monolayers using a size-selective permeability assay. Y-27632 enhanced EC
      monolayer barrier function due to a decline in small-pore number that was
      associated with increased EC surface area, reduced F-actin content, and
      reorganization of F-actin to beta-catenin-containing cell-cell adherens
      junctions. Although Y-27632 prevented thrombin-induced MLCP, stress fiber
      formation, and the increased phosphotyrosine content of paxillin and p125(FAK),
      it attenuated but did not prevent the thrombin-induced formation of large
      paracellular holes. These data indicate that thrombin-induced stress fiber
      formation is ROCK dependent. In contrast, thrombin-induced paracellular hole
      formation occurs in a ROCK-independent manner, whereas thrombin-induced monolayer
      hyperpermeability appears to be partially ROCK dependent.

PMID- 10898732
TI  - Cloning of murine glycosyl phosphatidylinositol anchor attachment protein, GPAA1.
AB  - Glycosyl phosphatidylinositols (GPIs) are used to anchor many proteins to the
      cell surface membrane and are utilized in all eukaryotic cells. GPI anchoring
      units are attached to proteins via a transamidase reaction mediated by a GPI
      transamidase complex. We isolated one of the components of this complex, mGPAA1
      (murine GPI anchor attachment), by the signal sequence trap method. mGPAA1 cDNA
      is about 2 kb in length and encodes a putative 621 amino acid protein. The mGPAA1
      gene has 12 small exons and 11 small introns. mGPAA1 mRNA is ubiquitously
      expressed in mammalian cells, and in situ hybridization analysis revealed that it
      is abundant in the choroid plexus, skeletal muscle, osteoblasts of rib, and
      occipital bone in mouse embryos. Its expression levels and transamidation
      efficiency decreased with differentiation of embryonic stem cells. The 3T3 cell
      lines expressing antisense mGPAA1 failed to express GPI-anchored proteins on the
      cell surface membrane.

PMID- 10898733
TI  - Cellular energetics analysis by a mathematical model of energy balance:
      estimation of parameters in human skeletal muscle.
AB  - Cellular energy balance requires that the physiological demands by ATP-utilizing
      functions be matched by ATP synthesis to sustain muscle activity. We devised a
      new method of analysis of these processes in data from single individuals. Our
      approach is based on the logic of current information on the major mechanisms
      involved in this energy balance and can quantify not directly measurable
      parameters that govern those mechanisms. We use a mathematical model that
      simulates by ordinary, nonlinear differential equations three components of
      cellular bioenergetics (cellular ATP flux, mitochondrial oxidative
      phosphorylation, and creatine kinase kinetics). We incorporate data under resting
      conditions, during the transition toward a steady state of stimulation and during
      the transition during recovery back to the original resting state. Making use of
      prior information about the kinetic parameters, we fitted the model to previously
      published dynamic phosphocreatine (PCr) and inorganic phosphate (P(i)) data
      obtained in normal subjects with an activity-recovery protocol using (31)P
      nuclear magnetic resonance spectroscopy. The experiment consisted of a baseline
      phase, an ischemic phase (during which muscle stimulation and PCr utilization
      occurred), and an aerobic recovery phase. The model described satisfactorily the
      kinetics of the changes in PCr and P(i) and allowed estimation of the maximal
      velocity of oxidative phosphorylation and of the net ATP flux in individuals both
      at rest and during stimulation. This work lays the foundation for a quantitative,
      model-based approach to the study of in vivo muscle energy balance in intact
      muscle systems, including human muscle.

PMID- 10898734
TI  - NO regulates PDGF-induced activation of PKB but not ERK in A7r5 cells:
      implications for vascular growth arrest.
AB  - In addition to the well-documented role of nitric oxide (NO) as a vasodilator, NO
      has also been implicated in vascular smooth muscle cell (VSMC) growth arrest.
      Signaling mechanisms responsible for growth factor receptor-mediated VSMC
      proliferation include the extracellular signal-regulated kinase (ERK) and
      possibly the protein kinase B (PKB) cascade. Thus the present study was designed
      to test the hypothesis that, in A7r5 vascular smooth muscle-derived cells,
      platelet-derived growth factor (PDGF)-induced activation of either ERK or PKB is
      regulated by NO, which then modulates cellular proliferation and/or apoptosis.
      PKB-alpha was the predominant isoform of PKB expressed in A7r5 cells and was also
      expressed in rabbit carotid arteries and aortae. Phosphorylation of PKB-alpha and
      ERK induced by PDGF-BB was maximal within 5-15 min in A7r5 cells. Preincubation
      of A7r5 cells with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) resulted
      in a biphasic regulation of PDGF-stimulated PKB-alpha phosphorylation and
      bioactivity. Acute exposure to SNAP significantly augmented PDGF-induced
      activation of PKB-alpha, whereas prolonged incubation led to a marked diminution
      in PDGF-induced activation of PKB-alpha. In contrast, SNAP did not affect PDGF
      induced activation of ERK at any time point. The cGMP-independent effects of SNAP
      on PDGF-induced activation of PKB-alpha were established with the use of an
      inhibitor of soluble guanylyl cyclase, ODQ, as well as a cell-permeable analog of
      cGMP, 8-bromo-cGMP. Prolonged treatment of A7r5 cells with SNAP led to a
      significant decrease in DNA synthesis without an appreciable increase in
      apoptosis. These data suggest that, after prolonged exposure to SNAP, NO
      selectively attenuates PDGF-induced increase in PKB-alpha activation, which in
      turn may contribute to diminished VSMC proliferation by mechanisms involving
      growth arrest but not apoptosis.

PMID- 10898735
TI  - LY-294002-inhibitable PI 3-kinase and regulation of baseline rates of Na(+)
      transport in A6 epithelia.
AB  - Blocker-induced noise analysis of epithelial Na(+) channels (ENaCs) was used to
      investigate how inhibition of an LY-294002-sensitive phosphatidylinositol 3
      kinase (PI 3-kinase) alters Na(+) transport in unstimulated and aldosterone
      prestimulated A6 epithelia. From baseline Na(+) transport rates (I(Na)) of 4.0 +/
      0.1 (unstimulated) and 9.1 +/- 0.9 microA/cm(2) (aldosterone), 10 microM LY
      294002 caused, following a relatively small initial increase of transport, a
      completely reversible inhibition of transport within 90 min to 33 +/- 6% and 38
      +/- 2% of respective baseline values. Initial increases of transport could be
      attributed to increases of channel open probability (P(o)) within 5 min to 143 +/
      17% (unstimulated) and 142 +/- 10% of control (aldosterone) from baseline P(o)
      averaging near 0.5. Inhibition of transport was due to much slower decreases of
      functional channel densities (N(T)) to 28 +/- 4% (unstimulated) and 35 +/- 3%
      (aldosterone) of control at 90 min. LY-294002 (50 microM) caused larger but
      completely reversible increases of P(o) (215 +/- 38% of control at 5 min) and
      more rapid but only slightly larger decreases of N(T). Basolateral exposure to LY
      294002 induced no detectable effect on transport, P(o) or N(T). We conclude that
      an LY-294002-sensitive PI 3-kinase plays an important role in regulation of
      transport by modulating N(T) and P(o) of ENaCs, but only when presented to apical
      surfaces of the cells.

PMID- 10898736
TI  - IL-4 and IL-13 upregulate arginase I expression by cAMP and JAK/STAT6 pathways in
      vascular smooth muscle cells.
AB  - The objectives of this study were to determine whether rat aortic smooth muscle
      cells (RASMC) express arginase and to elucidate the possible mechanisms involved
      in the regulation of arginase expression. The results show that RASMC contain
      basal arginase I (AI) activity, which is significantly enhanced by stimulating
      the cells with either interleukin (IL)-4 or IL-13, but arginase II (AII)
      expression was not detected under any condition studied here. We further
      investigated the signal transduction pathways responsible for AI induction. AI
      mRNA and protein levels were enhanced by addition of forskolin (1 microM) and
      inhibited by H-89 (30 microM), suggesting positive regulation of AI by a protein
      kinase A pathway. Genistein (10 microgramg/ml) and sodium orthovanadate
      (Na(3)VO(4); 10 microM) were used to investigate the role of tyrosine
      phosphorylation in the control of AI expression. Genistein inhibited, whereas
      Na(3)VO(4) enhanced the induction of AI by IL-4 or IL-13. Along with
      immunoprecipitation and immunoblot analyses, these data implicate the JAK/STAT6
      pathway in AI regulation. Dexamethasone (Dex) and interferon (IFN)-gamma were
      investigated for their effects on AI induction. Dex (1 microM) and IFN-gamma (100
      U/ml) alone had no effect on basal AI expression in RASMC, but both reduced AI
      induction by IL-4 and IL-13. In combination, Dex and IFN-gamma abolished AI
      induction by IL-4 and IL-13. Finally, both IL-4 and IL-13 significantly increased
      RASMC DNA synthesis as monitored by [(3)H]thymidine incorporation, demonstrating
      that upregulation of AI is correlated with an increase in cell proliferation.
      Blockade of AI induction by IFN-gamma, H-89, or genistein also blocked the
      increase in cell proliferation. These observations are consistent with the
      possibility that upregulation of AI might play an important role in the
      pathophysiology of vascular disorders characterized by excessive smooth muscle
      growth.

PMID- 10898737
TI  - Tenotomy decreases reporter protein synthesis via the 3'-untranslated region of
      the beta-myosin heavy chain mRNA.
AB  - We tested the hypothesis that the beta-myosin heavy chain (beta-MHC) 3'
      untranslated region (UTR) mediates decreased protein expression after tenotomy of
      the rat soleus. We also tested the hypothesis that decreased protein expression
      is the result of RNA-protein interactions within the 3'-UTR. beta-MHC was chosen
      for study because of its critical role in the function of postural muscles such
      as soleus. Adult rat soleus muscles were directly injected with luciferase (LUC)
      reporter constructs containing either the beta-MHC or SV40 3'-UTR. After 48 h of
      tenotomy, there was no significant effect on LUC expression in the SV40 3'-UTR
      group. In the beta-MHC 3'-UTR group, LUC expression was 37.3 +/- 4% (n = 5, P =
      0.03) of that in sham controls. Gel mobility shift assays showed that a protein
      factor specifically interacts with the beta-MHC 3'-UTR and that tenotomy
      significantly increases the level of this interaction (25 +/- 7%, n = 5, P =
      0.02). Thus the beta-MHC 3'-UTR is directly involved in decreased protein
      expression that is probably due to increased RNA-protein binding within the UTR.

PMID- 10898739
TI  - Force relaxes before the fall of cytosolic calcium in the photomechanical
      response of rat sphincter pupillae.
AB  - In the rat sphincter pupillae, as in other smooth muscles, the primary signal
      transduction cascade for agonist activation is receptor --> G protein -->
      phospholipase C --> inositol trisphosphate --> intracellular Ca(2+) concentration
      ([Ca(2+)](i)) --> calmodulin --> myosin light chain kinase --> phosphorylated
      myosin --> force development. Light stimulation of isolated sphincters pupillae
      can be very precisely controlled, and precise reproducible photomechanical
      responses (PMRs) result. This precision makes the PMR ideal for testing models of
      regulation of smooth muscle myosin phosphorylation. We measured force and
      [Ca(2+)](i) concurrently in sphincter pupillae following stimulation by light
      flashes of varying duration and intensity. We sampled at unusually short (0.01
      0.02 s) intervals to adequately test a PMR model based on the myosin
      phosphorylation cascade. We found, surprisingly, contrary to the behavior of
      intestinal muscle and predictions of the phosphorylation model, that during PMRs
      force begins to decay while [Ca(2+)](i) is still rising. We conclude that control
      of contraction in the sphincter pupillae probably involves an inhibitory process
      as well as activation by [Ca(2+)](i).

PMID- 10898738
TI  - VACM-1, a cullin gene family member, regulates cellular signaling.
AB  - Vasopressin-activated Ca(2+)-mobilizing (VACM-1) receptor binds arginine
      vasopressin (AVP) but does not have amino acid sequence homology with the
      traditional AVP receptors. VACM-1, however, is homologous with a newly discovered
      cullin family of proteins that has been implicated in the regulation of cell
      cycle through the ubiquitin-mediated degradation of cyclin-dependent kinase
      inhibitors. Because cell cycle processes can be regulated by the transmembrane
      signal transduction systems, the effects of VACM-1 expression on the Ca(2+) and
      cAMP-dependent signaling pathway were examined in a stable cell line expressing
      VACM-1 in VACM-1 transfected COS-1 cells and in cells cotransfected with VACM-1
      and the adenylyl cyclase-linked V(2) AVP receptor cDNAs. Expression of the VACM-1
      gene reduced basal as well as forskolin- and AVP-stimulated cAMP production. In
      cells cotransfected with VACM-1 and the V(2) receptor, the AVP- and forskolin
      induced increases in adenylyl cyclase activity and cAMP production were
      inhibited. The inhibitory effect of VACM-1 on cAMP production could be reversed
      by pretreating cells with staurosporin, a protein kinase A (PKA) inhibitor, or by
      mutating S730A, the PKA-dependent phosphorylation site in the VACM-1 sequence.
      The protein kinase C specific inhibitor Go-6983 further enhanced the inhibitory
      effect of VACM-1 on AVP-stimulated cAMP production. Finally, AVP stimulated D-myo
      inositol 1,4, 5-trisphosphate production both in the transiently transfected COS
      1 cells and in the stable cell line expressing VACM-1, but not in the control COS
      1 and Chinese hamster ovary cells. Our data demonstrate that VACM-1, the first
      mammalian cullin protein to be characterized, is involved in the regulation of
      signaling.

PMID- 10898740
TI  - Pathobiology of visceral pain: molecular mechanisms and therapeutic implications
      V. Central nervous system processing of somatic and visceral sensory signals.
AB  - Somatic and visceral sensation, including pain perception, can be studied
      noninvasively in humans with functional brain imaging techniques. Positron
      emission tomography and functional magnetic resonance imaging have identified a
      series of cerebral regions involved in the processing of somatic pain, including
      the anterior cingulate, insular, prefrontal, inferior parietal, primary and
      secondary somatosensory, and primary motor and premotor cortices, the thalamus,
      hypothalamus, brain stem, and cerebellum. Experimental evidence supports possible
      specific roles for individual structures in processing the various dimensions of
      pain, such as encoding of affect in the anterior cingulate cortex. Visceral
      sensation has been examined in the setting of myocardial ischemia, distension of
      hollow viscera, and esophageal acidification. Although knowledge regarding
      somatic sensation is more extensive than the information available for visceral
      sensation, important similarities have emerged between cerebral representations
      of somatic and visceral pain.

PMID- 10898741
TI  - Fibrogenesis I. New insights into hepatic stellate cell activation: the simple
      becomes complex.
AB  - Hepatic stellate cell activation is a complex process. Paradoxes and
      controversies include the origin(s) of hepatic stellate cells, the regulation of
      membrane receptor signaling and transcription, and the fate of the cells once
      liver injury resolves. Major themes have emerged, including the dominance of
      autocrine signaling and the identification of counterregulatory stimuli that
      oppose key features of activated cells. Advances in analytical methods including
      proteomics and gene array, coupled with powerful bioinformatics, promise to
      revolutionize how we view cellular responses. Our understanding of stellate cell
      activation is likely to benefit from these advances, unearthing modes of
      regulating cellular behavior that are not even conceivable on the basis of
      current paradigms.

PMID- 10898742
TI  - Iron-ascorbate alters the efficiency of Caco-2 cells to assemble and secrete
      lipoproteins.
AB  - Although oxidative stress has been implicated in development of gut pathologies,
      its role in intestinal fat transport has not been investigated. We assessed the
      effect of Fe(2+)-ascorbate-mediated lipid peroxidation on lipid synthesis,
      apolipoprotein biogenesis, and lipoprotein assembly and secretion. Incubation of
      postconfluent Caco-2 cells with iron(II)-ascorbate (0.2 mM/2 mM) in the apical
      compartment significantly promoted malondialdehyde formation without affecting
      sucrase activity, transepithelial resistance, DNA and protein content, and cell
      viability. However, addition of the oxygen radical-generating system reduced 1)
      [(14)C]oleic acid incorporation into cellular triglycerides (15%, P < 0.0002) and
      phospholipids (16%, P < 0.0005); 2) de novo synthesis of cellular apolipoprotein
      A-I (apo A-I) (18%, P < 0.05), apo A-IV (38%, P < 0.05), and apo B-48 (45%, P <
      0.003) after [(35)S]methionine addition; and 3) production of chylomicrons (50%),
      VLDL (40%), LDL (37%), and HDL (30%) (all P < 0.0001). In contrast, increased
      total cellular cholesterol formation (96%, P < 0.0001), assayed by [(14)C]acetate
      incorporation, was noted, attributable to marked elevation (70%, P < 0.04) in
      activity of DL-3-hydroxy-3-methyl-glutaryl-CoA reductase, the rate-limiting
      enzyme in cholesterol synthesis. The ratio of Acyl-CoA to cholesterol
      acyltransferase, the esterifying cholesterol enzyme, remained unchanged. Fe(2+)
      ascorbate-mediated lipid peroxidation modifies intracellular fat absorption and
      may decrease enterocyte efficiency in assembling and transporting lipids during
      gut inflammation.

PMID- 10898743
TI  - Functional and molecular biological evidence of SGLT-1 in the ruminal epithelium
      of sheep.
AB  - Because of the effective catabolism of D-glucose to short-chain fatty acids by
      intraruminal microorganisms, the absorption of D-glucose from the rumen was
      thought to be of minor importance. However, clinical studies suggested that
      significant quantities of D-glucose are transported from the ruminal contents to
      the blood. We therefore tested the ruminal epithelium of sheep for the presence
      of Na(+)-glucose cotransporter 1 (SGLT-1) on both the functional and mRNA levels.
      In the absence of an electrochemical gradient, 3-O-methylglucose (3-OMG) was net
      absorbed across isolated ruminal epithelia mounted in Ussing chambers. The net
      transport of 3-OMG followed Michaelis-Menten kinetics and was sensitive to
      phlorizin or decreasing Na(+) concentrations. The mucosal addition of 10 mM D
      glucose induced an immediate, phlorizin-sensitive increase in short-circuit
      current (I(sc)). I(sc) could also be increased by serosal addition of D-glucose
      or D-mannose, but electrogenic uptake of D-glucose or 3-OMG added on the mucosal
      side was still detectable after serosal stimulation of I(sc). RT-PCR using
      primers specific for the ovine intestinal SGLT-1 with subsequent TA cloning and
      sequencing revealed 100% identity between the cloned cDNA and mRNA fragment 187
      621 of ovine intestinal SGLT-1. In conclusion, the ruminal epithelium has a high
      affinity SGLT-1, which indicates that it maintains the capacity for D-glucose
      absorption.

PMID- 10898744
TI  - Cardiac excitation-contraction coupling in the portal hypertensive rat.
AB  - Basal contractility and responses to beta-adrenoceptor activation are compromised
      in hearts from rats with chronic portal vein stenosis. Here we report the effect
      of partial ligation of the portal vein on myocardial G protein expression, beta
      adrenoceptor-G protein coupling, and excitation-contraction coupling (ECC).
      Contractility (dT/dt) was reduced 30-50% in right and left ventricles, but the
      rate of relaxation (-dT/dt) was unaffected. Isoproterenol-induced positive
      inotropism was diminished, but there was no difference in ED(50). The
      concentration-dependent increase in -dT/dt was unaffected. G(s)alpha and
      G(i)alpha expression, cholera toxin- and pertussis toxin-induced ADP
      ribosylation, and formation of the agonist-receptor-G(s) complex were unaffected
      by portal vein stenosis. Of the components of ECC examined, the caffeine
      sensitive sarcoplasmic reticulum Ca(2+) pool was reduced 35%, although the Ca(2+)
      uptake and release processes were unchanged; the apparent density of L-type
      Ca(2+) channels decreased 60% with no change in affinity; the dihydropyridine
      Ca(2+) channel agonist BAY K 8644 produced relative changes in dT/dt that were
      similar in both groups, suggesting normal function in the remaining Ca(2+)
      channels; and Na(+)/Ca(2+) exchange was reduced 50% in the portal vein stenosis
      group. These data suggest that the effect of portal vein stenosis on the
      myocardium is the result of alterations to ECC.

PMID- 10898745
TI  - Agonist-induced cytoplasmic volume changes in cultured rabbit parietal cells.
AB  - Concomitant Na(+)/H(+) and Cl(-)/HCO(3)(-) exchange activation occurs during
      stimulation of acid secretion in cultured rabbit parietal cells, possibly related
      to a necessity for volume regulation during the secretory process. We
      investigated whether cytoplasmic volume changes occur during secretagogue
      stimulation of cultured rabbit parietal cells. Cells were loaded with the
      fluorescent dye calcein, and the calcein concentration within a defined
      cytoplasmic volume was recorded by confocal microscopy. Forskolin at 10(-5) M,
      carbachol at 10(-4) M, and hyperosmolarity (400 mosmol) resulted in a rapid
      increase in the cytoplasmic dye concentration by 21 +/- 6, 9 +/- 4, and 23 +/-
      5%, respectively, indicative of cell shrinkage, followed by recovery to baseline
      within several minutes, indicative of regulatory volume increase (RVI).
      Depolarization by 5 mM barium resulted in a decrease of the cytoplasmic dye
      concentration by 10 +/- 2%, indicative of cell swelling, with recovery within 15
      min, and completely prevented forskolin- or carbachol-induced cytoplasmic
      shrinkage. Na(+)/H(+) exchange inhibitors slightly reduced the initial cell
      shrinkage and significantly slowed the RVI, whereas 100 microM bumetanide had no
      significant effect on either parameter. We conclude that acid secretagoguges
      induce a rapid loss of parietal cell cytoplasmic volume, followed by RVI, which
      is predominantly mediated by Na(+)/H(+) and Cl(-)/HCO(3)(-) exchange.

PMID- 10898746
TI  - Manometric changes during retrograde biliary infusion in mice.
AB  - The manometric, ultrastructural, radiographic, and physiological consequences of
      retrograde biliary infusion were determined in normostatic and cholestatic mice.
      Intraluminal biliary pressure changed as a function of infusion volume, rate, and
      viscosity. Higher rates of constant infusion resulted in higher peak intraluminal
      biliary pressures. The pattern of pressure changes observed was consistent with
      biliary ductular and/or canalicular filling followed by leakage at a threshold
      pressure. Retrograde infusion with significant elevations in pressure led to
      paracellular leakage of lanthanum chloride, radiopaque dye, and [(14)C]sucrose
      with rapid systemic redistribution via sinusoidal and subsequent hepatic venous
      drainage. Chronic extrahepatic bile duct obstruction resulted in significantly
      smaller peak intrabiliary pressures and lower levels of paracellular leakage.
      These findings indicate that under both normostatic and cholestatic conditions
      elevated intrabiliary volumes/pressures result in an acute pressure-dependent
      physical opening of tight junctions, permitting the movement of infusate from the
      intrabiliary space into the subepithelial tissue compartment. Control of
      intraluminal pressure may potentially permit the selective delivery of
      macromolecules >18-20 A in diameter to specific histological compartments.

PMID- 10898747
TI  - The contractile action of platelet-activating factor on gallbladder smooth
      muscle.
AB  - Platelet-activating factor (PAF) may be a mediator of some sequelae of
      cholecystitis, a disorder with gallbladder motor dysfunction. The aims of this
      study were to determine the effect and mechanism of PAF on gallbladder muscle.
      Exogenous administration of PAF-16 or PAF-18 caused dose-dependent contractions
      of gallbladder muscle strips in vitro with threshold doses of 1 ng/ml and 10
      ng/ml, respectively. The PAF-induced contractions were not significantly reduced
      by TTX, atropine, or hexamethonium but were significantly inhibited with the PAF
      receptor antagonists ginkolide B and CV-3988. The PAF-induced contraction was
      reduced by indomethacin. Preventing influx of extracellular calcium with a
      calcium-free solution nearly abolished the PAF contractile response. Nifedipine
      inhibited the PAF contractile response, whereas ryanodine had no effect.
      Pertussis toxin reduced the PAF contractile response. In conclusion, PAF causes
      gallbladder contraction through specific PAF receptors on gallbladder muscle.
      These PAF receptors appear to be linked to a prostaglandin-mediated mechanism and
      to pertussis toxin-sensitive G proteins. The contractile response is largely
      mediated through the utilization of extracellular calcium influx through voltage
      dependent calcium channels.

PMID- 10898748
TI  - Functional vagal input to gastric myenteric plexus as assessed by vagal
      stimulation-induced Fos expression.
AB  - Immunohistochemical detection of c-Fos expression was used to identify gastric
      myenteric plexus neurons that receive excitatory input from vagal efferent
      neurons activated by electrical stimulation of the cervical vagi in anesthetized
      rats. Vagal stimulation-induced Fos expression increased with higher pulse
      frequency, so that with 16 Hz (rectangular pulses of 1 mA/0.5 ms for 30 min)
      approximately 30% and with 48 Hz 90% of all neurons near the lesser curvature
      were Fos positive. In sham-stimulated rats there was no Fos expression. The
      percentage of Fos-activated neurons was only slightly smaller (85% with 48 Hz)
      near the greater curvature. Prior atropine administration (1 mg/kg ip) had little
      effect on vagal stimulation-induced Fos expression, and in unilaterally
      stimulated rats there was no Fos expression on the contralateral (noninnervated)
      side of the stomach, ruling out mediation by gastric motility or secretory
      responses. However, polysynaptic recruitment of third- and higher-order neurons
      cannot be ruled out completely. These results support the idea that, at least in
      the stomach, functional excitatory innervation of myenteric plexus neurons by the
      efferent vagus is profuse and widespread, refuting the notion of only a few vagal
      "command neurons."

PMID- 10898749
TI  - CGRP modulates mucin synthesis in surface mucus cells of rat gastric oxyntic
      mucosa.
AB  - We examined the effects of the calcitonin gene-related peptide (CGRP), including
      the possible participation of nitric oxide (NO), on mucin biosynthesis in the
      surface epithelium and remaining deep mucosa as well as the entire mucosa and
      compared the distribution of CGRP and NO synthase (NOS) using a combination of
      double immunofluorescence labeling and multiple dye filter. Pieces of tissue
      obtained from the corpus and antrum were incubated in a medium containing
      [(3)H]glucosamine and CGRP, with or without the NOS inhibitor. CGRP dose
      dependently enhanced [(3)H]glucosamine incorporation into the corpus mucin but
      had no effect on antral mucin biosynthesis. The CGRP receptor antagonist, CGRP-(8
      37), prevented the increase in (3)H-labeled corpus mucin. This stimulation of
      corpus mucin synthesis disappeared after removal of the surface mucus cell layer.
      CGRP activated the mucin biosynthesis in the surface mucus cells. In the full
      thickness corpus mucosa, CGRP-induced activation was completely blocked by the
      NOS inhibitor. CGRP-immunoreactive fibers were intertwined within the surface
      mucus cell layer with type I NOS immunoreactivity. These results show that CGRP
      stimulated mucin biosynthesis mediated by NO is limited to surface mucus cells of
      the rat gastric oxyntic mucosa.

PMID- 10898750
TI  - Spontaneously developing chronic colitis in IL-10/iNOS double-deficient mice.
AB  - Mice deficient in both inducible nitric oxide synthase (iNOS) and interleukin
      (IL)-10 (iNOS(-/-)/IL-10(-/-)) were created to examine the role of iNOS in
      spontaneously developing intestinal inflammation. IL-10(-/-)/iNOS(-/-) mice were
      compared with IL-10(-/-) (iNOS(+/+)) littermates over 6 mo. RT-PCR, Western blot
      analysis, and immunohistochemistry were performed to measure iNOS message and
      protein levels. Plasma nitrate/nitrite (NO(x)) levels were assessed by HPLC.
      Damage scores (macroscopic and microscopic) and granulocyte infiltration were
      assessed. At 3-4 wk, IL-10(-/-) and IL-10(-/-)/iNOS(-/-) mice had no signs of
      colonic inflammation or granulocyte infiltration. Plasma NO(x) levels were not
      different from controls. By 3-4 mo, IL-10(-/-) mice had increased damage scores
      and granulocyte infiltration concurrent with increased mRNA and protein synthesis
      (restricted to the epithelium) for iNOS in intestinal tissues but not other
      tissues. Plasma NO(x) levels increased fivefold. Interestingly, in the absence of
      iNOS induction or increased plasma NO(x), iNOS(-/-)/IL-10(-/-) mice had damage
      and granulocyte infiltration equivalent to those observed in IL-10(-/-)
      littermates. These data suggest that iNOS does not impact on the development or
      severity of spontaneous chronic inflammation in IL-10-deficient mice.

PMID- 10898751
TI  - Kupffer cell-derived prostaglandin E(2) is involved in alcohol-induced fat
      accumulation in rat liver.
AB  - Destruction of Kupffer cells with gadolinium chloride (GdCl(3)) and intestinal
      sterilization with antibiotics diminished ethanol-induced steatosis in the
      enteral ethanol feeding model. However, mechanisms of ethanol-induced fatty liver
      remain unclear. Accordingly, the role of Kupffer cells in ethanol-induced fat
      accumulation was studied. Rats were given ethanol (5 g/kg body wt)
      intragastrically, and tissue triglycerides were measured enzymatically. Kupffer
      cells were isolated 0-24 h after ethanol, and PGE(2) production was measured by
      ELISA, whereas inducible cyclooxygenase (COX-2) mRNA was detected by RT-PCR. As
      expected, ethanol increased liver triglycerides about threefold. This increase
      was blunted by antibiotics, GdCl(3), the dihydropyridine-type Ca(2+) channel
      blocker nimodipine, and the COX inhibitor indomethacin. Ethanol also increased
      PGE(2) production by Kupffer cells about threefold. This increase was also
      blunted significantly by antibiotics, nimodipine, and indomethacin. Furthermore,
      tissue triglycerides were increased about threefold by PGE(2) treatment in vivo
      as well as by a PGE(2) EP(2)/EP(4) receptor agonist, whereas an EP(1)/EP(3)
      agonist had no effect. Moreover, permeable cAMP analogs also increased
      triglyceride content in the liver significantly. We conclude that PGE(2) derived
      from Kupffer cells, which are activated by ethanol, interacts with prostanoid
      receptors on hepatocytes to increase cAMP, which causes triglyceride accumulation
      in the liver. This mechanism is one of many involved in fatty liver caused by
      ethanol.

PMID- 10898752
TI  - Luminal ammonia retards restitution of guinea pig injured gastric mucosa in
      vitro.
AB  - The present study was conducted to elucidate the mechanisms by which Helicobacter
      pylori (HP)-derived ammonia causes gastric mucosal injury. Intact sheets of
      guinea pig gastric fundic mucosae were incubated in Ussing chambers. Both the
      luminal and the serosal pH were kept at 7.4. Transmucosal potential difference
      (PD) and electrical resistance (R) were monitored as indices of mucosal
      integrity. Restitution was evaluated by recovery of PD, R, and transmucosal
      [(3)H]mannitol flux after Triton X-100-induced mucosal injury. The effects of
      luminal or serosal NH(4)Cl on function and morphology of uninjured or injured
      mucosae were examined. In uninjured mucosae, serosal NH(4)Cl induced more
      profound decreases in PD and R and more prominent vacuolation in gastric
      epithelial cells than did luminal NH(4)Cl. In contrast, luminal NH(4)Cl markedly
      inhibited restitution in injured mucosae and caused an extensive vacuolation in
      gastric epithelial cells, as did serosal NH(4)Cl. Transmucosal ammonia flux was
      greater in the injured than in the uninjured mucosae. These results suggest that
      1) basolateral membrane of gastric epithelial cells is more permeable to ammonia
      than apical membrane and 2) luminal ammonia, at concentrations detected in HP
      infected gastric lumen, retards restitution in injured mucosae.

PMID- 10898753
TI  - Mechanism of the alcohol cyclic pattern: role of the hypothalamic-pituitary
      thyroid axis.
AB  - The cause of the cycle of urinary alcohol levels (UALs) in rats fed ethanol
      continually at a fixed rate is unknown. Rats were fed ethanol intragastrically at
      a constant dose for 2 mo, and daily body temperatures and UALs were recorded.
      Body temperature cycled inversely to UAL, suggesting that the rate of metabolism
      could be mechanistically involved in the rate of ethanol elimination during the
      cycle. To document this, whole body O(2) consumption rate was monitored daily
      during the cycle. The rate of O(2) consumption correlated positively with the
      change in body temperature and negatively with the change in UAL. Since the
      metabolic rate responds to changes in body temperature, thyroid hormone levels
      were measured during the UAL cycle. T(4) levels correlated positively with the
      O(2) consumption rate and negatively with the UALs. In a second experiment using
      propylthiouracil treatment, UALs did not cycle and a fall in body temperature
      failed to stimulate an increase in the rate of ethanol elimination. Consequently,
      rats died of overdose. Likewise, in a third experiment using rats with severed
      pituitary stalks, UALs failed to cycle and rats died of overdose. From these
      observations it was concluded that the UAL cycle depends on an intact
      hypothalamic-pituitary-thyroid axis response to the ethanol-induced drop in body
      temperature by increasing the rate of ethanol elimination.

PMID- 10898754
TI  - Primary structures of PYY, [Pro(34)]PYY, and PYY-(3-36) confer different
      conformations and receptor selectivity.
AB  - We synthesized PYY-(1-36) (nonselective between Y(1) and Y(2) receptor subtype
      agonists), [Pro(34)]PYY (selective for Y(1)), and PYY-(3-36) (selective for Y(2))
      to determine whether solution conformation plays a role in receptor subtype
      selectivity. The three peptides exhibited the expected specificities in
      displacing labeled PYY-(1-36) from cells transfected with Y(1) receptors
      (dissociation constants = 0.42, 0.21, and 1,050 nM, respectively) and from cells
      transfected with Y(2) receptors (dissociation constants = 0.03, 710, and 0.11 nM,
      respectively) for PYY-(1-36), [Pro(34)]PYY, and PYY-(3-36). Sedimentation
      equilibrium analyses revealed that the three PYY analogs were 80-90% monomer at
      the concentrations used for the subsequent circular dichroism (CD) and (1)H
      nuclear magnetic resonance (NMR) studies. CD analysis measured helicities for PYY
      (1-36), [Pro(34)]PYY, and PYY-(3-36) of 42%, 31%, and 24%, suggesting distinct
      differences in secondary structure. The backbone (1)H-NMR resonances of the three
      peptides further substantiated marked conformational differences. These patterns
      support the hypothesis that Y(1) and Y(2) receptor subtype binding affinities
      depend on the secondary and tertiary solution state structures of PYY and its
      analogs.

PMID- 10898755
TI  - Extracellular UTP stimulates electrogenic bicarbonate secretion across CFTR
      knockout gallbladder epithelium.
AB  - The loss of cystic fibrosis transmembrane conductance regulator (CFTR)-mediated
      transepithelial HCO(3)(-) secretion contributes to the pathogenesis of pancreatic
      and biliary disease in cystic fibrosis (CF) patients. Recent studies have
      investigated P2Y(2) nucleotide receptor agonists, e.g., UTP, as a means to bypass
      the CFTR defect by stimulating Ca(2+)-activated Cl(-) secretion. However, the
      value of this treatment in facilitating transepithelial HCO(3)(-) secretion is
      unknown. Gallbladder mucosae from CFTR knockout mice were used to isolate the
      Ca(2+)-dependent anion conductance during activation of luminal P2Y(2) receptors.
      In Ussing chamber studies, UTP stimulated a transient peak in short-circuit
      current (I(sc)) that declined to a stable plateau phase lasting 30-60 min. The
      plateau I(sc) after UTP was Cl(-) independent, HCO(3)(-) dependent, insensitive
      to bumetanide, and blocked by luminal DIDS. In pH stat studies, luminal UTP
      increased both I(sc) and serosal-to-mucosal HCO(3)(-) flux (J(s-->m)) during a 30
      min period. Substitution of Cl(-) with gluconate in the luminal bath to inhibit
      Cl(-)/HCO(3)(-) exchange did not prevent the increase in J(s-->m) and I(sc)
      during UTP. In contrast, luminal DIDS completely inhibited UTP-stimulated
      increases in J(s-->m) and I(sc). We conclude that P2Y(2) receptor activation
      results in a sustained (30-60 min) increase in electrogenic HCO(3)(-) secretion
      that is mediated via an intracellular Ca(2+)-dependent anion conductance in CF
      gallbladder.

PMID- 10898756
TI  - A cortical evoked potential study of afferents mediating human esophageal
      sensation.
AB  - The aim of this study was to compare the characteristics of esophageal cortical
      evoked potentials (CEP) following electrical and mechanical stimulation in
      healthy subjects to evaluate the afferents involved in mediating esophageal
      sensation. Similarities in morphology and interpeak latencies of the CEP to
      electrical and mechanical stimulation suggest that they are mediated via similar
      pathways. Conduction velocity of CEP to either electrical or mechanical
      stimulation was 7.9-8.6 m/s, suggesting mediation via thinly myelinated Adelta
      fibers. Amplitudes of CEP components to mechanical stimulation were significantly
      smaller than to electrical stimulation at the same levels of perception, implying
      that electrical stimulation activates a larger number of afferents. The latency
      delay of approximately 50 ms for each mechanical CEP component compared with the
      corresponding electrical CEP component is consistent with the time delay for the
      mechanical stimulus to distend the esophageal wall sufficiently to trigger the
      afferent volley. In conclusion, because the mechanical and electrical stimulation
      intensities needed to obtain esophageal CEP are similar and clearly perceived, it
      is likely that both spinal and vagal pathways mediate esophageal CEP. Esophageal
      CEP to both modalities of stimulation are mediated by myelinated Adelta-fibers
      and produce equally robust CEP responses. Both techniques may have important
      roles in the assessment of esophageal sensory processing in health and disease.

PMID- 10898757
TI  - Pancreatic CCK(B) receptors: their potential roles in somatostatin release and
      delta-cell proliferation.
AB  - In rodents, cholecystokinin (CCK) induces pancreatic enzyme secretion and
      pancreas growth through its CCK(A) receptors. It is unknown whether occupation of
      the CCK(B) receptors present in pig and human pancreas can cause the same
      effects. This study evaluates CCK(B) receptor expression in rat, mouse, pig, and
      fetal human pancreata using Northern blot, Western blot, and immunofluorescence
      techniques. The reported 2.7-kb CCK(B) receptor mRNA transcript in the rat brain
      and gastric fundus is absent in pancreas; the message was, however, detected by
      RT-PCR and by a CCK(B) receptor antibody as an 80-kDa protein present uniquely in
      islet delta-cells. Proteins of 50 and 80 kDa appear in mouse pancreas, and
      proteins of 50 and 115 kDa appear in pig and human pancreas, respectively, all
      localized in islet delta-cells. Gastrin mRNAs are strongly present in fetal rat
      pancreas, and the hormone is localized in islets; both are repressed 10 days
      after birth. In conclusion, the CCK(B) receptors are present in pancreas of four
      species with exclusive location in islet delta-cells. In such a location, they
      could be indirectly involved in the control of enzyme secretion.

PMID- 10898758
TI  - Triggering of transient LES relaxations in ferrets: role of sympathetic pathways
      and effects of baclofen.
AB  - Activation of gastric vagal mechanoreceptors by distention is thought to be the
      trigger for transient lower esophageal sphincter relaxations (TLESR), which lead
      to gastroesophageal reflux. The contribution of higher-threshold gastric
      splanchnic mechanoreceptors is uninvestigated. GABA(B) receptor agonists,
      including baclofen, potently reduce triggering of TLESR by low-level gastric
      distention. We aimed to determine first whether this effect of baclofen is
      maintained at high-level distention and second the role of splanchnic pathways in
      triggering TLESR. Micromanometric/pH studies in conscious ferrets showed that
      intragastric glucose infusion (25 ml) increased triggering of TLESR and reflux.
      Both were significantly reduced by baclofen (7 micromol/kg ip) (P < 0.05). When
      40 ml of air was added to the glucose infusion, more TLESR occurred than with
      glucose alone (P < 0.01). These were also reduced by baclofen (P < 0.001). TLESR
      after glucose/air infusion were assessed before and after splanchnectomy (2-4, 9
      11, and 23-25 days), which revealed no change. Baclofen inhibits TLESR after both
      low- and high-level gastric distention. Splanchnic pathways do not contribute to
      increased triggering of TLESR by high-level gastric distention.

PMID- 10898759
TI  - Hepatic preconditioning preserves energy metabolism during sustained ischemia.
AB  - We evaluated the possibility that ischemic preconditioning could modify hepatic
      energy metabolism during ischemia. Accordingly, high-energy nucleotides and their
      degradation products, glycogen and glycolytic intermediates and regulatory
      metabolites, were compared between preconditioned and nonpreconditioned livers.
      Preconditioning preserved to a greater extent ATP, adenine nucleotide pool, and
      adenylate energy charge; the accumulation of adenine nucleosides and bases was
      much lower in preconditioned livers, thus reflecting slower adenine nucleotide
      degradation. These effects were associated with a decrease in glycogen depletion
      and reduced accumulation of hexose 6-phosphates and lactate. 6-Phosphofructo-2
      kinase decreased in both groups, reducing the availability of fructose-2, 6
      bisphosphate. Preconditioning sustained metabolite concentration at higher levels
      although this was not correlated with an increased glycolytic rate, suggesting
      that adenine nucleotides and cAMP may play the main role in the modulation of
      glycolytic pathway. Preconditioning attenuated the rise in cAMP and limited the
      accumulation of hexose 6-phosphates and lactate, probably by reducing glycogen
      depletion. Our results suggest the induction of metabolic arrest and/or
      associated metabolic downregulation as energetic cost-saving mechanisms that
      could be induced by preconditioning.

PMID- 10898760
TI  - Attenuated febrile response to lipopolysaccharide in rats with biliary
      obstruction.
AB  - Patients with biliary tract obstruction have unexplained, inordinately high rates
      of perioperative morbidity and mortality, whereas cholestatic animals display
      abnormal hypothalamic responses to pyrogenic stimuli. We asked if obstructive
      cholestasis was associated with abnormal fever generation. Male Sprague-Dawley
      rats (250 g) underwent laparotomy for implantation of thermistors and either bile
      duct resection (BDR) or sham operation. After recovery, temperatures were
      recorded by telemetry and conscious, unrestrained rats in each group were
      injected intraperitoneally with either interleukin-1beta (IL-1beta;1 microg/kg)
      or Escherichia coli lipopolysaccharide (LPS; 50 microg/kg). Baseline temperatures
      in both groups were similar. Febrile responses after IL-1beta injection in BDR
      and sham groups were not significantly different. However, in response to LPS
      injection, BDR rats showed an initial hypothermia with a subsequently attenuated
      febrile response. Administration of anti-tumor necrosis factor-alpha (TNF-alpha)
      antibody 2 h before LPS injection blocked the LPS-induced hypothermia seen in BDR
      animals. However, serum levels of TNF-alpha were not significantly different
      between sham and BDR animals after LPS injection at any time point measured (0,
      1.5, and 3 h).

PMID- 10898761
TI  - Changes in methionine adenosyltransferase and S-adenosylmethionine homeostasis in
      alcoholic rat liver.
AB  - Liver-specific and non-liver-specific methionine adenosyltransferase (MAT) are
      products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation
      of S-adenosylmethionine (SAM). We previously showed that MAT2A expression was
      associated with more rapid cell growth. Changes in MAT expression have not been
      examined in animal models of alcoholic liver injury, which is the focus of the
      current study. After rats were fed intragastrically with ethanol and high fat for
      9 wk, the mRNA level of both MAT forms doubled but only the protein level of
      MAT2A increased. Although liver-specific MAT activity did not change, it was 32%
      lower after one and 68% lower after eight weekly enteral doses of
      lipopolysaccharide. Hepatic levels of methionine, SAM, and DNA methylation fell
      by approximately 40%. c-myc was hypomethylated, and its mRNA level increased.
      Genome-wide DNA strand break increased. Thus in the prefibrotic stage of
      alcoholic liver injury, there is already a switch in MAT expression, global DNA
      hypomethylation, increased c-myc expression, and genome-wide DNA strand break.
      These changes may be important in predisposing this liver disease to malignant
      degeneration.

PMID- 10898762
TI  - Enteric microflora contribute to constitutive ICAM-1 expression on vascular
      endothelial cells.
AB  - Quantitative estimates of endothelial cell adhesion molecule expression have
      revealed that some adhesion molecules [e.g., intercellular adhesion molecule-1
      (ICAM-1)] are abundantly expressed in different vascular beds under normal
      conditions. The objective of this study was to determine whether the enteric
      microflora contribute to the constitutive expression of ICAM-1 and other
      endothelial cell adhesion molecules in the gastrointestinal tract and other
      regional vascular beds. The dual radiolabeled monoclonal antibody technique was
      used to measure endothelial expression of ICAM-1, ICAM-2, vascular cell adhesion
      molecule-1 (VCAM-1), and E-selectin in conventional, germ-free mice and germ-free
      mice receiving the cecal contents of conventional mice to reestablish the enteric
      microflora (total association). Constitutive ICAM-1 expression was significantly
      lower in the splanchnic organs (pancreas, stomach, small and large intestine,
      mesentery, and liver), kidneys, skeletal muscle, and skin of germ-free mice
      compared with their conventional counterparts. These differences were abolished
      after total association of germ-free mice with the indigenous gastrointestinal
      flora. The expression of ICAM-2, VCAM-1, and E-selectin in the various tissues
      studied did not differ between conventional and germ-free mice. These findings
      indicate that the indigenous gastrointestinal microflora are responsible for a
      significant proportion of the basal ICAM-1 expression detected in both intestinal
      and extraintestinal tissues.

PMID- 10898763
TI  - Treatment of gastric ulcers and diarrhea with the Amazonian herbal medicine
      sangre de grado.
AB  - Sangre de grado is an Amazonian herbal medicine used to facilitate the healing of
      gastric ulcers and to treat gastritis, diarrhea, skin lesions, and insect stings.
      This study was designed to evaluate the gastrointestinal applications. Gastric
      ulcers were induced in rats by brief serosal exposure of the fundus to acetic
      acid (80%). Sangre de grado was administered in drinking water at 1:1,000 and
      1:10,000 dilutions from the postoperative period to day 7. Guinea pig ileum
      secretory responses to capsaicin, electrical field stimulation, and the
      neurokinin-1 (NK-1) agonist [Sar(9),Met(O(2))(11)]substance P were examined in
      Ussing chambers. Sangre de grado facilitated the healing of experimental gastric
      ulcer, reducing myeloperoxidase activity, ulcer size, and bacterial content of
      the ulcer. The expression of proinflammatory genes tumor necrosis factor-alpha,
      inducible nitric oxide synthase (iNOS), interleukin (IL)-1beta, IL-6, and
      cyclooxygenase-2 was upregulated by ulcer induction but reduced by sangre de
      grado treatment, particularly iNOS and IL-6. In Ussing chambers, sangre de grado
      impaired the secretory response to capsaicin but not to electrical field
      stimulation or the NK-1 agonist. We conclude that sangre de grado is a potent,
      cost-effective treatment for gastrointestinal ulcers and distress via
      antimicrobial, anti-inflammatory, and sensory afferent-dependent actions.

PMID- 10898765
TI  - The endothelin system in normal human colon.
AB  - Endothelin (ET)-1 is a potent vasoconstrictor and mitogenic peptide that has a
      variety of biological effects in noncardiovascular tissues. The precise cellular
      distribution of the ET-1 system in the wall of the normal human colon was studied
      to identify the physiological role of ET in the gut. In situ hybridization
      revealed ET-converting enzyme-1 (ECE-1) mRNA in all vessels, the colon
      epithelium, and macrophages. Prepro-ET-1 (PPET-1) mRNA had a similar distribution
      except for a scattered signal in mucosal microvessels. ET(A) and ET(B) receptor
      mRNAs were mainly in the lamina propria, pericryptal myofibroblasts,
      microvessels, and mononuclear cells, with ET(A) mRNA more abundant than ET(B)
      mRNA. (125)I-ET-1 binding showed ET(B) along the crypts and in nerve fibers
      descending from the ganglionic plexus that contained PPET-1, ECE-1, and ET(B)
      transcripts, whereas glia contained ET(A) receptors. The finding of the entire ET
      system in the normal mucosa suggests its implication in some characteristic
      functions of the colon and its secretion as both a neuroactive and a vasoactive
      peptide.

PMID- 10898764
TI  - Sustained muscle contraction induced by agonists, growth factors, and Ca(2+)
      mediated by distinct PKC isozymes.
AB  - The role of protein kinase C (PKC) in sustained contraction was examined in
      intestinal circular and longitudinal muscle cells. Initial contraction induced by
      agonists (CCK-8 and neuromedin C) was abolished by 1) inhibitors of Ca(2+)
      mobilization (neomycin and dimethyleicosadienoic acid), 2) calmidazolium, and 3)
      myosin light chain (MLC) kinase (MLCK) inhibitor KT-5926. In contrast, sustained
      contraction was not affected by these inhibitors but was abolished by 1) the PKC
      inhibitors chelerythrine and calphostin C, 2) PKC-epsilon antibody, and 3) a
      pseudosubstrate PKC-epsilon inhibitor. GDPbetaS abolished both initial and
      sustained contraction, whereas a Galpha(q/11) antibody inhibited only initial
      contraction, implying that sustained contraction was dependent on activation of a
      distinct G protein. Sustained contraction induced by epidermal growth factor was
      inhibited by calphostin C, PKC-alpha,beta,gamma antibody, and a pseudosubstrate
      PKC-alpha inhibitor. Ca(2+) (0.4 microM) induced an initial contraction in
      permeabilized muscle cells that was blocked by calmodulin and MLCK inhibitors and
      a sustained contraction that was blocked by calphostin C and a PKC
      alpha,beta,gamma antibody. Thus initial contraction induced by Ca(2+), agonists,
      and growth factors is mediated by MLCK, whereas sustained contraction is mediated
      by specific Ca(2+)-dependent and -independent PKC isozymes. G protein-coupled
      receptors are linked to PKC activation via distinct G proteins.

PMID- 10898766
TI  - Increased nuclear translocation of catalytically active PKC-zeta during mouse
      colonocyte hyperproliferation.
AB  - Protein kinase (PK) C-zeta is implicated in the control of colonic epithelial
      cell proliferation in vitro. However, less is known about its physiological role
      in vivo. Using the transmissible murine colonic hyperplasia (TMCH) model, we
      determined its expression, subcellular localization, and kinase activity during
      native crypt hyperproliferation. Enhanced mitosis was associated with increased
      cellular 72-kDa holoenzyme (PKC-zeta, 3.2-fold), 48-kDa catalytic subunit (PKM
      zeta, 3- to 9-fold), and 24-kDa membrane-bound fragment (M(f)-zeta, >10-fold)
      expression. Both PKC-zeta and PKM-zeta exhibited intrinsic kinase activity, and
      substrate phosphorylation increased 4.5-fold. No change in cellular PKC-iota/PKM
      iota expression occurred. The subcellular distribution of immunoreactive PKC-zeta
      changed significantly: neck cells lost their basal subcellular pole filamentous
      staining, whereas proliferating cell nuclear antigen-positive cells exhibited
      elevated cytoplasmic, lateral membrane, and nuclear staining. Subcellular
      fractionation revealed increased PKC-zeta and PKM-zeta expression and activity
      within nuclei, which preferentially accumulated PKM-zeta. These results suggest
      separate cellular and nuclear roles, respectively, for PKC-zeta in quiescent and
      mitotically active colonocytes. PKM-zeta may specifically act as a modulator of
      proliferation during TMCH.

PMID- 10898768
TI  - Plant genetic diversity in the Canary Islands: a conservation perspective.
AB  - The Canary Islands are an Atlantic volcanic archipelago with a rich flora of ~570
      endemic species. The endemics represent ~40% of the native flora of the islands,
      and ~20% of the endemics are in the E (endangered) category of the International
      Union for Conservation of Nature. A review of allozyme variation in 69 endemic
      species belonging to 18 genera and eight families is presented. The average
      species-level genetic diversity (H(T)) at allozyme loci is 0.186, which is twice
      as high as the mean reported for endemics of Pacific archipelagos. Possible
      factors contributing to this higher diversity are discussed, but the reasons
      remain obscure. An average of 28% of the allozyme diversity within species
      resides among populations, indicating a high level of interpopulational
      differentiation. Studies of reproductive biology indicate that many of the
      endemic species are outcrossers. The high total diversity within species, the
      relatively high differentiation among populations, and the outcrossing breeding
      systems have implications for species conservation. Decreased population sizes in
      outcrossing species would promote biparental inbreeding and increase inbreeding
      depression. The relatively high proportion of allozyme diversity among
      populations indicates that the most effective strategy for preserving genetic
      variation in species is to conserve as many populations as possible. The genetic
      diversity in many Canary Island endemics is endangered by: (1) overgrazing by
      introduced animals, such as barbary sheep, goats, mouflons, rabbits, and sheep;
      (2) interspecific hybridization following habitat disturbance or planting of
      endemics along roadsides or in public gardens; (3) competition with alien plant
      species; and (4) decline of population size because of urban development and
      farming.

PMID- 10898769
TI  - Observations on the mature gametophyte of Phylloglossum (Lycopodiaceae).
AB  - Mature, gametangia-bearing photosynthetic gametophytes of Phylloglossum can be
      grown from the nonphotosynthetic, cylindrical, negatively gravitropic immature
      stages in illuminated axenic culture on a nutrient medium with or without 0.2%
      glucose. The gametangial-bearing region of these gametophytes, the photosynthetic
      crown, grows horizontally from the apex of the immature cylindrical stage. At
      maturity the photosynthetic crown is thickened and bilaterally symmetrical. It is
      usually narrow and bean-shaped with dorsal and ventral regions. Occasionally, the
      ventral region becomes thicker and the crown is deltoid in cross section. The
      dorsal edge or ridge of the crown is the gametangial region with archegonia and
      antheridia. The gametangia are often hidden because they are interspersed among
      numerous uni- or bicellular paraphyses. The lateral surfaces below the
      gametangial region lack outgrowths, and the ventral region is covered with long
      rhizoids. The apical meristem at the anterior end of the crown is overarched by
      the developing dorsal tissue of the gametangial ridge. The lower derivatives of
      the meristem form the ventral region with rhizoids. Phylloglossum gametophytes
      are unusual because their mode of organic nutrition changes from mycorrhizal to
      photosynthetic during ontogeny.

PMID- 10898767
TI  - Cyclooxygenase-2-derived prostaglandin D(2) is an early anti-inflammatory signal
      in experimental colitis.
AB  - The ability of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2
      inhibitors to exacerbate inflammatory bowel disease suggests that prostaglandins
      are important anti-inflammatory mediators in this context. Prostaglandin D(2) has
      been suggested to exert anti-inflammatory effects. We investigated the
      possibility that prostaglandin D(2) derived from cyclooxygenase-2 plays an
      important role in downregulating colonic inflammation in rats. Colitis was
      induced by intracolonic administration of trinitrobenzene sulfonic acid. At
      various times thereafter (from 1 h to 7 days), colonic prostaglandin synthesis
      and myeloperoxidase activity (index of granulocyte infiltration) were measured.
      Prostaglandin D(2) synthesis was elevated >4-fold above controls within 1-3 h of
      induction of colitis, preceding significant granulocyte infiltration. Treatment
      with a selective cyclooxygenase-2 inhibitor abolished the increase in
      prostaglandin D(2) synthesis and caused a doubling of granulocyte infiltration.
      Colonic granulocyte infiltration was significantly reduced by administration of
      prostaglandin D(2) or a DP receptor agonist (BW-245C). These results demonstrate
      that induction of colitis results in a rapid increase in prostaglandin D(2)
      synthesis via cyclooxygenase-2. Prostaglandin D(2) downregulates granulocyte
      infiltration into the colonic mucosa, probably through the DP receptor.

PMID- 10898770
TI  - Cleistogamous capitulum in Centaurea melitensis (Asteraceae): heterochronic
      origin.
AB  - Cleistogamous capitula formed by Centaurea melitensis display a number of
      morphological and functional changes with respect to chasmogamous capitula that
      ensure self-fertilization. Because no studies have hitherto addressed the
      evolution of cleistogamy in Asteraceae, it was considered useful to ascertain
      whether these changes are attributable to one or more of the heterochronic
      processes reported in the literature. Bivariate allometric analyses were
      performed, and changes were represented graphically using Gould's clock models
      for size, shape, and age of several capitulum and floret structures. Results
      suggest that the partially paedomorphic appearance of cleistogamous with respect
      to chasmogamous capitula is attributable to three processes: (1) early onset of
      floral development (predisplacement), (2) decreased growth rate of the whorls
      studied (except gynoecium width) and (3) early offset time (progenesis). The
      latter appears to play the most significant role in the origin of the
      cleistogamous capitulum.

PMID- 10898771
TI  - Stamen development in the Ericaceae. I. Anther wall, microsporogenesis,
      inversion, and appendages.
AB  - Development of the introrse, tetrasporangiate, and normally dorsifixed and
      poricidal stamens has been studied at the gross morphological and cellular level
      in ten species of Ericaceae. Microsporogenesis, followed in four species, is
      normal, with cytokinesis simultaneous, forming tetrahedral tetrads. The
      tricolp(or)ate pollen is shed as permanent tetrads with each segment two-celled
      except in Enkianthus in which pollen grains are three-celled monads. Anther-wall
      development is similar in all four species initially, but no regular pattern of
      wall development could be recognized thereafter. The tapetum, of parietal origin,
      is binucleate, glandular, and mainly uniseriate. Viscin threads occur with the
      tetrads in the three rhododendroid species. A well-developed endothecium appears
      only in Enkianthus.Soon after stamen initiation, anthers of nine species invert
      at the eventual filament-anther junction to become introrse; in Enkianthus
      inversion occurs close to anthesis. Microsporogenesis starts during early
      inversion; greater cell elongation on the abaxial side of the young anther
      completes inversion by the late sporogenous-tissue stage. In Erica and, to a
      lesser extent Calluna, inversion results from greater abaxial than adaxial
      increase in cell number and length just above the filament-anther junction. The
      single vascular strand reflects the degree of inversion. Stamens of six species
      are appendaged; three have only awns, two only spurs, while one has both.
      Appendages arise from residual meristems after inversion is completed (or almost
      so) in all except Enkianthus. Awns develop at what will be the apex at maturity
      of each anther half. Their length and orientation vary among species. Only in
      Vaccinium do the awns become hollow (tubules). Spurs, varying in length, shape,
      and size, arise on the abaxial side from the filament, connective, or thecae.

PMID- 10898772
TI  - Plant growth and phosphorus accumulation of wild type and two root hair mutants
      of Arabidopsis thaliana (Brassicaceae).
AB  - Arabidopsis thaliana root hairs grow longer and denser in response to low
      phosphorus availability. We tested the hypothesis that wild-type Arabidopsis
      would acquire more phosphorus under phosphorus-limiting conditions than mutants
      that do not have the root hair response. The growth and phosphorus acquisition of
      wild-type Arabidopsis (WS) were compared to two root hair mutants (rhd6 and rhd2)
      under eight phosphorus treatments ranging from 0.4 mmol/m to 54 mmol/m
      phosphorus. At the lowest phosphorus treatment, all plants were small and showed
      severe phosphorus stress symptoms. At 1.5 mmol/m phosphorus, WS plants had
      greater shoot biomass, absolute growth rate, total phosphorus, and specific
      phosphorus absorption than the two root hair mutants. At the highest phosphorus
      treatment, there was no difference between genotypes in any of the parameters
      measured. We conclude that the response of increased root hair growth under low
      phosphorus availability in Arabidopsis is important in increasing phosphorus
      acquisition under phosphorus-limiting conditions.

PMID- 10898773
TI  - The efficiency of Arabidopsis thaliana (Brassicaceae) root hairs in phosphorus
      acquisition.
AB  - Arabidopsis thaliana root hairs grow longer and denser in response to low
      phosphorus availability. In addition, plants with the root hair response acquire
      more phosphorus than mutants that have root hairs that do not respond to
      phosphorus limiting conditions. The purpose of this experiment was to determine
      the efficiency of root hairs in phosphorus acquisition at high- and low
      phosphorus availability. Root hair growth, root growth, root respiration, plant
      phosphorus uptake, and plant phosphorus content of 3-wk-old wild-type Arabidopsis
      (WS) were compared to two root hair mutants (rhd6 and rhd2) under high (54
      mmol/m) and low (0.4 mmol/m) phosphorus availability. A cost-benefit analysis was
      constructed from the measurements to determine root hair efficiency. Under high
      phosphorus availability, root hairs did not have an effect on any of the
      parameters measured. Under low-phosphorus availability, wild-type Arabidopsis had
      greater total root surface area, shoot biomass, phosphorus per root length, and
      specific phosphorus uptake. The cost-benefit analysis shows that under low
      phosphorus, wild-type roots acquire more phosphorus for every unit of carbon
      respired or unit of phosphorus invested into the roots than the mutants. We
      conclude that the response of root hairs to low-phosphorus availability is an
      efficient strategy for phosphorus acquisition.

PMID- 10898774
TI  - Organogenesis from internode-derived nodules of Humulus lupulus var. Nugget
      (Cannabinaceae): histological studies and changes in the starch content.
AB  - The sequence of histological and histochemical events occurring during
      organogenesis from Humulus lupulus var. Nugget internode-derived nodules was
      studied. Sections were made and studies were carried out from the start of
      culture treatment until the development of shoot buds. Cell division was observed
      in both cambial and cortical regions during the first week of culture
      establishment. Cell division in cortical cells led to the formation of an
      incipient callus tissue. From the calluses prenodular structures of cambial
      origin appeared and gave rise to nodules from which shoot buds formed. Nodules
      kept separating into "daughter nodules" from which arose an increasing number of
      shoot buds. Iodide staining showed a strong starch accumulation in callus tissue
      and in prenodular structures. During shoot-bud primordia formation starch content
      decreased in nodules. Some starch was also noted in control explants (cultured on
      basal medium), however at a lower level than that observed in explants cultured
      on media with growth regulators. Shoot-bud regeneration was not observed in
      control explants.

PMID- 10898775
TI  - Pollination ecology of Anthyllis vulneraria subsp. vulgaris (Fabaceae): nectar
      robbers as pollinators.
AB  - This paper examines the hypothesis that nectar robbing can affect plant
      reproductive success either positively or negatively. To this end, I investigated
      various aspects of the pollination ecology of a population of the herb Anthyllis
      vulneraria subsp. vulgaris in northwest Spain over 5 yr. By observing floral
      visitors, I found that the most important pollinator species was the long-tongued
      bee Anthophora acervorum, which accounted for ~45% of recorded insect visits.
      However, just over 45% of visits were by the nectar-robbing bumble bees Bombus
      terrestris and B. jonellus. Although the incidence of robbing differed
      considerably over 5 yr of study, the frequency in every season was very high
      (66.4-76.5% of robbing) except for 1997 (0% robbing). Despite this high frequency
      of robbing, robbed flowers had a higher probability of setting fruit than
      nonrobbed flowers in all years of the study (mean: 82.0 vs. 51.0%; excluding
      1997). This increased fruit set in robbed flowers is directly related to bumble
      bee behavior because the robbers' bodies came into contact with both the anthers
      and stigmas while robbing. Thus, the robbers effect pollination. These results
      suggest that the effect of nectar robbers on plant reproductive success is
      dependent both on the robbers' behavior and on flower/inflorescence structure.
      The importance of nectar-robbing bumble bees on the reproductive success of A.
      vulneraria and its yearly high frequency suggest that the relationship between
      robbers and this plant is part of a successful long-term mutualism.

PMID- 10898777
TI  - Is the Prunella (Lamiaceae) hybrid zone structured by an environmental gradient?
      Evidence from a reciprocaltransplant experiment.
AB  - Hybrid zones may be structured by environmentally independent selection against
      intrinsically unfit hybrids (tension zone models), or by environmentally
      dependent fitness differences among parental species and hybrids (ecological
      selection-gradient models). A 30-m slope in a mountain grassland harbors a hybrid
      zone of the clonal perennials, Prunella grandiflora and P. vulgaris (Lamiaceae),
      with P. grandiflora in the upper, P. vulgaris in the lower, and both parental
      species and P. grandiflora * P. vulgaris Hybrids in a narrow middle part. We
      found gradients for soil depth and water content, and vegetation height and
      biomass along the slope. A reciprocal transplant experiment yielded crossing
      reaction norms for vegetative reproduction. Parental species were locally adapted
      to their home sites, while the three taxa did not differ in vegetative
      reproduction in the Hybrid transplant site. Local adaptation for vegetative
      reproduction of P. grandiflora was mediated through higher survival and that of
      P. vulgaris through higher ramet number, indicating adaptation of their clonal
      growth strategies (phalanx vs. guerrilla) to the different habitats. Hybrid
      performance was intermediate between that of the parental species in all three
      sites, although Hybrids flowered more often than the parental species in the
      Hybrid site. Our results support ecological selection-gradient rather than
      tension zone models.

PMID- 10898776
TI  - Competitive suppression of Quercus douglasii (Fagaceae) seedling emergence and
      growth.
AB  - Reduced recruitment of blue oak (Quercus douglasii) seedlings in California
      grasslands and woodlands may result from shifts in seasonal soil water
      availability coincident with replacement of the native perennial herbaceous
      community by Mediterranean annuals. We used a combination of container and field
      experiments to examine the interrelationships between soil water potential,
      herbaceous neighborhood composition, and blue oak seedling shoot emergence and
      growth. Neighborhoods of exotic annuals depleted soil moisture more rapidly than
      neighborhoods of a perennial grass or "no-neighbor" controls. Although effects of
      neighborhood composition on oak seedling root elongation were not statistically
      significant, seedling shoot emergence was significantly inhibited in the annual
      neighborhoods where soil water was rapidly depleted. Seedling water status
      directly reflected soil water potential, which also determined the extent and
      duration of oak seedling growth during the first year. End-of-season seedling
      height significantly influenced survival and growth in subsequent years. While
      growth and survival of blue oak seedlings may be initially constrained by
      competition with herbaceous species, subsequent competition with adult blue oak
      trees may further contribute to reduced sapling recruitment.

PMID- 10898778
TI  - Pollination ecology of Agave macroacantha (Agavaceae) in a Mexican tropical
      desert. I. Floral biology and pollination mechanisms.
AB  - In a study of sexual reproduction in long-lived semelparous plants, we observed
      Agave macroacantha in the tropical desert of Tehuacan-Cuicatlan, Mexico,
      describing duration of flowering, flower phenology, and nectar production
      patterns. We also performed two manipulative experiments evaluating (a) the seed
      production efficiency of different crossing systems (selfing, cross-pollination,
      apomixis, and control), and (b) the effect of different pollinators (diurnal
      exposure to pollinators, nocturnal exposure, exclusion, and control) on the seeds
      produced. Flowering occurred from early May to late July and had a mean duration
      of 29 days in the individual rosettes. The flowers were protandrous; anthesis
      occurred in the afternoon of the third day after floral opening, and the pistils
      matured in the afternoon of the fifth day. The stigmas remained receptive from
      dusk to the following morning. Pollination was mostly allogamous. Nectar was
      produced principally during the night, from the first stages of floral aperture
      until the stigmas wilted and flowering ceased. The flowers were visited during
      the day by hymenoptera, butterflies, and hummingbirds and during the night by
      bats and moths. Only the nocturnal visitors, however, were successful
      pollinators. Agave macroacantha is extremely dependent on nocturnal pollinators
      for its reproductive success.

PMID- 10898779
TI  - Pollination ecology of Agave macroacantha (Agavaceae) in a Mexican tropical
      desert. II. The role of pollinators.
AB  - We did a series of observational studies and manipulative experiments on the
      guild of nocturnal visitors of Agave macroacantha, including (1) a description of
      the hourly patterns of visits by moths and bats, (2) an evaluation of the
      relative contribution of bats and moths to flowering success, and (3) an
      evaluation of the pollination efficiency of the different bat species. Scapes
      exposed to moths but excluded to bats yielded ~50% fewer fruits than those
      exposed to both pollinator groups. Flowers exposed to the bat species
      Leptonycteris curasoae showed similar fruiting success to those exposed to
      Choeronycteris mexicana and to those exposed to the whole nocturnal visitor
      guild. However, the fruits originated from flowers pollinated by Leptonycteris
      curasoae yielded significantly more seed than those exposed to Choeronycteris
      mexicana or to the whole pollinator guild. It is concluded that Agave
      macroacantha is extremely dependent on nocturnal pollinators for its reproductive
      success and that bats are especially important for successful pollination. Some
      of these pollinators are migratory and have been reported to be steadily
      declining. A continuing decline in the populations of pollinators may impede the
      successful sexual reproduction of the plant host and may put the long-term
      survival of this agave species under risk.

PMID- 10898780
TI  - Phylogeny of the Neotropical Alibertia group (Rubiaceae), with emphasis on the
      genus Alibertia, inferred from ITS and 5S ribosomal DNA sequences.
AB  - Phylogenetic relationships of 38 species of the Alibertia group (Rubiaceae) and
      two outgroup species were investigated using the nuclear ribosomal 5S
      nontranscribed spacer (5S-NTS) and the internal transcribed spacers (ITS).
      Analysis of the data sets separately and in combination resulted in several well
      supported and congruent groupings. However, the three analyses yielded different
      results as to the branching order of the basal clades. With the exception of
      Alibertia hispida, the species in the genus Alibertia appear in one weakly to
      moderately supported clade. This clade is in turn composed of two strongly
      supported subclades. One comprises several Alibertia species, including the type
      (A. edulis), three Borojoa species, and Randia tessmannii. The other subclade
      consists of Alibertia species only. This division is also generally supported
      morphologically by fruit size, corolla size, number of corolla lobes, and pollen
      aperture (porate vs. colporate). The sister group to the Alibertia clade
      comprises Duroia with Amaioua species internested. The close relationship of
      Ibetralia and Kutchubaea is corroborated. In addition, Alibertia hispida is a
      member of this strongly supported clade. Likewise, the two "Genipa" species are
      supported as a monophyletic group in 100% of the bootstrap replicates. It is
      concluded that the 5S spacer is superior to the commonly used ITS region in terms
      of resolution and robustness among closely related taxa.

PMID- 10898781
TI  - Phylogenetic relationships within the Gentianales based on NDHF and RBCL
      sequences, with particular reference to the Loganiaceae.
AB  - Phylogenetic relationships in the Gentianales with focus on Loganiaceae sensu
      lato are evaluated using parsimony analyses of nucleotide sequence data from the
      plastid genes rbcL and ndhF. Inter- and intrafamilial relationships in the
      Gentianales, which consist of the families Apocynaceae (including
      Asclepiadaceae), Gelsemiaceae, Gentianaceae, Loganiaceae, and Rubiaceae, are
      studied and receive increased support from the combination of rbcL and ndhF data,
      which indicate that the family Rubiaceae forms the sister group to the
      successively nested Gentianaceae, Apocynaceae, and Loganiaceae, all of which are
      well supported. The family Gelsemiaceae forms a distinct, supported group sister
      to Apocynaceae. The Loganiaceae sensu stricto form a strongly supported group
      consisting of 13 genera: Antonia, Bonyunia, Gardneria, Geniostoma, Labordia,
      Logania, Mitrasacme, Mitreola, Neuburgia, Norrisia, Spigelia, Strychnos, and
      Usteria. These genera form two well-supported lineages. Several members of
      Loganiaceae sensu Leeuwenberg and Leenhouts, i.e., Androya, Peltanthera,
      Plocosperma, Polypremum, and Sanango are clearly not members of the Gentianales.
      The earlier exclusion of Buddlejaceae (including Buddleja, Emorya, Gomphostigma,
      and Nicodemia) as well as the reclassification of the genera Nuxia and Retzia to
      Stilbaceae of the Lamiales are all well supported.

PMID- 10898782
TI  - Relationships within Cupressaceae sensu lato: a combined morphological and
      molecular approach.
AB  - Parsimony analysis of matK and rbcL sequence data, together with a nonmolecular
      database, yielded a well-resolved phylogeny of Cupressaceae sensu lato. Monophyly
      of Cupressaceae sensu stricto is well supported, and separate northern and
      southern hemisphere subclades are resolved, with Tetraclinis within the northern
      subclade; there is no support for any of the tribes sensu Li. Taxodiaceae
      comprise five separate lineages. Chamaecyparis nootkatensis falls within
      Cupressus, clustering with a robust clade of New World species. Libocedrus Florin
      is paraphyletic and should incorporate Pilgerodendron. Evolution of several
      characters of wood and leaf anatomy and chemistry is discussed in light of this
      estimate of the phylogeny; numerous parallelisms are apparent. A new
      infrafamilial classification is proposed in which seven subfamilies are
      recognized: Callitroideae Saxton, Athrotaxidoideae Quinn, Cunninghamioideae
      (Sieb. & Zucc.) Quinn, Cupressoideae Rich. ex Sweet, Sequoioideae (Luerss.)
      Quinn, Taiwanioideae (Hayata) Quinn, Taxodioideae Endl. ex K. Koch. The rbcL
      sequence for Taxodium distichum is corrected, and the implications for a
      previously published estimate of the minimum rate of divergence of the gene since
      the Miocene are highlighted.

PMID- 10898783
TI  - Cytology and mating systems in the climbing cacti Hylocereus and Selenicereus.
AB  - Chromosome numbers and meiotic behavior are reported for the climbing cacti
      species Hylocereus undatus, Hylocereus polyrhizus, and Selenicereus megalanthus.
      The Hylocereus spp. are diploid (2n = 22), while S. megalanthus is a tetraploid
      (2n = 44). Irregular chromosome disjunction at anaphase I in pollen mother cells
      of S. megalanthus is probably the major cause of its reduced pollen viability and
      may contribute to low seed set, low number of viable seeds and, consequently, low
      fruit mass. A pollination study confirmed self-incompatibility in H. polyrhizus
      and a weakened incompatibility reaction in H. undatus and S. megalanthus. Major
      crossability barriers do not exist between the Hylocereus spp. investigated.
      Reciprocal intergeneric crosses were successful between Hylocereus spp. and S.
      megalanthus, suggesting that an Hylocereus sp. might be one of the diploid
      progenitors of the tetraploid S. megalanthus. The implications of the results on
      cacti nomenclature and systematics are briefly discussed.

PMID- 10898784
TI  - Origin of Livistona chinensis var. subglobosa (Arecaceae) on the "islet of the
      gods": Aoshima, Japan.
AB  - RAPD analysis was performed to discuss the origin of Livistona chinensis var.
      subglobosa using samples from eight localities, Iriomotejima, Ishigakijima,
      Okinawa, Yakushima, Tanegashima, Cape Sata, Tsukishima, and Aoshima, in Japan.
      Random amplified polymorphic DNA (RAPD) markers were obtained using five random
      primers and analyzed by the unweighted pair group method arithmetic (UPGMA). Data
      from Iriomotejima clustered with data from Aoshima, suggesting the possibility
      that seeds or green woods were carried by the tidal current from the southern
      fields of Iriomotejima to Aoshima.

PMID- 10898785
TI  - Lineage commitment in the immune system: the T helper lymphocyte grows up.

PMID- 10898786
TI  - Mitf from neural crest to melanoma: signal transduction and transcription in the
      melanocyte lineage.

PMID- 10898787
TI  - Complete lack of NF-kappaB activity in IKK1 and IKK2 double-deficient mice:
      additional defect in neurulation.
AB  - NF-kappaB activity is induced by cytokines, stress, and pathogens. IKK1 and IKK2
      are critical IkappaB kinases in NF-kappaB activation. In this study mice lacking
      IKK1 and IKK2 died at E12. Additional defect in neurulation associated with
      enhanced apoptosis in the neuroepithelium was also observed. MEF cells from IKK1(
      /-)/IKK2(-/-) embryos did not respond to NF-kappaB inducers. Upon crossing with
      kappaB-lacZ transgenic mice, double-deficient embryos also lost lacZ transgene
      expression in vascular endothelial cells during development. Our data suggest
      that IKK1 and IKK2 are essential for NF-kappaB activation in vivo and have an
      important role in protecting neurons against excessive apoptosis during
      development.

PMID- 10898788
TI  - Bcl-2 antiapoptotic protein mediates verotoxin II-induced cell death: possible
      association between bcl-2 and tissue failure by E. coli O157:H7.
AB  - Verotoxin II (VTII: or Shiga-like toxin 2) is a key factor for Escherichia coli
      O157:H7-induced multiple tissue failure and contains a pentameric sequence
      (NWGRI) similar to the Bcl-2 homolog domain, BH1. In the current study, we
      demonstrate that VTII, but not VTI, interacts with Bcl-2 through each BH1 domain
      pentameric sequence (NWGRI) and that the VTII/Bcl-2 complex is necessary for cell
      death induction in target cells. VTII translocates to mitochondria and induces
      cell death only when target cells are expressing Bcl-2. In addition, interruption
      of VTII-Bcl-2 complex formation by a pentameric BH1 synthetic peptide suppresses
      VTII-induced cell death. In the present article, we propose that Bcl-2 mediates
      VTII-induced target cell death by the interaction with each pentameric sequence
      of BH1 domain.

PMID- 10898789
TI  - Inhibition of Wnt signaling by ICAT, a novel beta-catenin-interacting protein.
AB  - Wnt signaling has an important role in both embryonic development and
      tumorigenesis. beta-Catenin, a key component of the Wnt signaling pathway,
      interacts with the TCF/LEF family of transcription factors and activates
      transcription of Wnt target genes. Here, we identify a novel beta-catenin
      interacting protein, ICAT, that was found to inhibit the interaction of beta
      catenin with TCF-4 and represses beta-catenin-TCF-4-mediated transactivation.
      Furthermore, ICAT inhibited Xenopus axis formation by interfering with Wnt
      signaling. These results suggest that ICAT negatively regulates Wnt signaling via
      inhibition of the interaction between beta-catenin and TCF and is integral in
      development and cell proliferation.

PMID- 10898790
TI  - Sexual dimorphism in diverse metazoans is regulated by a novel class of
      intertwined zinc fingers.
AB  - Sex determination is regulated by diverse pathways. Although upstream signals
      vary, a cysteine-rich DNA-binding domain (the DM motif) is conserved within
      downstream transcription factors of Drosophila melanogaster (Doublesex) and
      Caenorhabditis elegans (MAB-3). Vertebrate DM genes have likewise been identified
      and, remarkably, are associated with human sex reversal (46, XY gonadal
      dysgenesis). Here we demonstrate that the structure of the Doublesex domain
      contains a novel zinc module and disordered tail. The module consists of
      intertwined CCHC and HCCC Zn(2+)-binding sites; the tail functions as a nascent
      recognition alpha-helix. Mutations in either Zn(2+)-binding site or tail can lead
      to an intersex phenotype. The motif binds in the DNA minor groove without sharp
      DNA bending. These molecular features, unusual among zinc fingers and zinc
      modules, underlie the organization of a Drosophila enhancer that integrates sex-
      and tissue-specific signals. The structure provides a foundation for analysis of
      DM mutations affecting sexual dimorphism and courtship behavior.

PMID- 10898791
TI  - Drosophila double parked: a conserved, essential replication protein that
      colocalizes with the origin recognition complex and links DNA replication with
      mitosis and the down-regulation of S phase transcripts.
AB  - We identified a Drosophila gene, double parked (dup), that is essential for DNA
      replication and belongs to a new family of replication proteins conserved from
      Schizosaccharomyces pombe to humans. Strong mutations in dup cause embryonic
      lethality, preceded by a failure to undergo S phase during the postblastoderm
      divisions. dup is required also for DNA replication in the adult ovary,
      establishing that dup is needed for DNA replication at multiple stages of
      development. Strikingly, DUP protein colocalizes with the origin recognition
      complex to specific sites in the ovarian follicle cells. This suggests that DUP
      plays a direct role in DNA replication. The dup transcript is cell cycle
      regulated and is under the control of E2F and Cyclin E. Interestingly, dup mutant
      embryos fail both to downregulate S phase genes and to engage a checkpoint
      preventing mitosis until completion of S phase. This could be either because
      these events depend on progression of S phase beyond the point blocked in the dup
      mutants or because DUP is needed directly for these feedback mechanisms.

PMID- 10898792
TI  - The Saccharomyces telomere-binding protein Cdc13p interacts with both the
      catalytic subunit of DNA polymerase alpha and the telomerase-associated est1
      protein.
AB  - Saccharomyces telomeres consist of approximately 350 bp of C(1-3)A/TG(1-3) DNA.
      Most of this approximately 350 bp is replicated by standard, semiconservative DNA
      replication. After conventional replication, the C(1-3)A strand is degraded to
      generate a long single strand TG(1-3) tail that can serve as a substrate for
      telomerase. Cdc13p is a single strand TG(1-3) DNA-binding protein that localizes
      to telomeres in vivo. Genetic data suggest that the Cdc13p has multiple roles in
      telomere replication. We used two hybrid analysis to demonstrate that Cdc13p
      interacted with both the catalytic subunit of DNA polymerase alpha, Pol1p, and
      the telomerase RNA-associated protein, Est1p. The association of these proteins
      was confirmed by biochemical analysis using full-length or nearly full-length
      proteins. Point mutations in either CDC13 or POL1 that reduced the Cdc13p-Pol1p
      interaction resulted in telomerase mediated telomere lengthening. Over-expression
      of the carboxyl terminus of Est1p partially suppressed the temperature sensitive
      lethality of a cdc13-1 strain. We propose that Cdc13p's interaction with Est1p
      promotes TG(1-3) strand lengthening by telomerase and its interaction with Pol1p
      promotes C(1-3)A strand resynthesis by DNA polymerase alpha.

PMID- 10898793
TI  - Long palindromes formed in Streptomyces by nonrecombinational intra-strand
      annealing.
AB  - Long inverted repeats (palindromes) are ubiquitous among prokaryotic and
      eukaryotic genomes. Earlier work has implicated both DNA breaks and short
      inverted repeats (IRs) in the formation of long palindromes in yeast and
      Tetrahymena by a proposed mechanism of intramolecular recombination. Here we
      report that long-palindromic linear plasmids are formed in Streptomyces following
      double strand DNA breakage by a nonrecombinational intra-strand annealing process
      that also involves IRs. By modification of palindrome-generating linear plasmids
      and development of a novel procedure that enables the sequencing of palindrome
      junctions, we show that long-palindrome formation occurs by unimolecular intra
      strand annealing of IRs followed by 3' extension of the resulting DNA fold-back.
      The consequent hairpin structures serve as templates for synthesis of duplex
      linear plasmids containing long palindromes. We suggest that this model for long
      palindrome formation in Streptomyces may represent a generally applicable
      mechanism for generating DNA palindromes.

PMID- 10898794
TI  - Disruption of the ARF transcriptional activator DMP1 facilitates cell
      immortalization, Ras transformation, and tumorigenesis.
AB  - The DMP1 transcription factor induces the ARF tumor suppressor gene in mouse
      fibroblasts, leading to cell cycle arrest in a p53-dependent manner. We disrupted
      sequences encoding the DNA-binding domain of DMP1 in mouse embryonic stem cells
      and derived animals lacking the functional protein. DMP1-null animals are small
      at birth, and males develop more slowly than their wild-type littermates. Some
      adult animals exhibit seizures and/or obstuctive uropathy, each of unknown cause.
      The growth of explanted DMP1-null mouse embryo fibroblasts (MEFs) is
      progressively retarded as cells are passaged in culture on defined transfer
      protocols; but, unlike the behavior of normal cells, p19(ARF), Mdm2, and p53
      levels remain relatively low and DMP1-null MEFs do not senesce. Whereas the
      establishment of cell lines from MEFs is usually always accompanied by either p53
      or ARF loss of function, continuously passaged DMP1-null cells readily give rise
      to established 3T3 and 3T9 cell lines that retain wild-type ARF and functional
      p53 genes. Early-passage DMP1-null cells, like MEFs from either ARF-null or p53
      null mice, can be morphologically transformed by oncogenic Ha-Ras (Val-12) alone.
      Splenic lymphocytes harvested from both DMP1-null and ARF-null mice exhibit
      enhanced proliferative responses in long-term cultures when stimulated to divide
      with antibody to CD3 and interleukin-2. Although only 1 of 40 DMP1-null animals
      spontaneously developed a tumor in the first year of life, neonatal treatment
      with dimethylbenzanthracene or ionizing radiation induced tumors of various
      histologic types that were not observed in similarly treated DMP1(+/+) animals.
      Karyotypic analyses of MEFs and lymphomas from DMP1-null animals revealed
      pseudodiploid chromosome numbers, consistent with the retention of wild-type p53.
      Together, these data suggest that ARF function is compromised, but not
      eliminated, in animals lacking functional DMP1.

PMID- 10898796
TI  - Novel gene expressed in nasal region influences outgrowth of olfactory axons and
      migration of luteinizing hormone-releasing hormone (LHRH) neurons.
AB  - Although a variety of cues have been implicated in axonal targeting during
      embryogenesis and regeneration, the precise mechanisms guiding olfactory axons
      remain unclear. Appropriate olfactory axon pathfinding is essential for
      functional chemoreceptive and pheromone receptive systems. Olfactory axon
      pathfinding is also necessary for establishment of the neuroendocrine LHRH
      system, cells critical for reproductive function. LHRH cells exhibit neurophilic
      migration moving from the nasal region along olfactory axons into the brain.
      Factors involved in the migration of these neuroendocrine cells are as yet
      unresolved. We report identification of a novel factor termed nasal embryonic
      LHRH factor (NELF) that was discovered in a differential screen of migrating
      versus nonmigrating primary LHRH neurons. NELF is expressed in PNS and CNS
      tissues during embryonic development, including olfactory sensory cells and LHRH
      cells. NELF antisense experiments indicate that a reduction in NELF expression
      decreases olfactory axon outgrowth and the number of LHRH neurons that migrate
      out of the nasal tissue. These results demonstrate that NELF plays a role as a
      common guidance molecule for olfactory axon projections and subsequently, either
      directly or indirectly, in the neurophilic migration of LHRH cells.

PMID- 10898795
TI  - BCoR, a novel corepressor involved in BCL-6 repression.
AB  - BCL-6 encodes a POZ/zinc finger transcriptional repressor that is required for
      germinal center formation and may influence apoptosis. Aberrant expression of BCL
      6 due to chromosomal translocations is implicated in certain subtypes of non
      Hodgkin's lymphoma. The POZ domains of BCL-6 and several other POZ proteins
      interact with corepressors N-CoR and SMRT. Here we identify and characterize a
      novel corepressor BCoR (BCL-6 interacting corepressor), which is expressed
      ubiquitously in human tissues. BCoR can function as a corepressor when tethered
      to DNA and, when overexpressed, can potentiate BCL-6 repression. Specific class I
      and II histone deacetylases (HDACs) interact in vivo with BCoR, suggesting that
      BCoR may functionally link these two classes of HDACs. Strikingly, BCoR interacts
      selectively with the POZ domain of BCL-6 but not with eight other POZ proteins
      tested, including PLZF. Additionally, interactions between the BCL-6 POZ domain
      and SMRT, N-CoR, and BCoR are mutually exclusive. The specificity of the BCL
      6/BCoR interaction suggests that BCoR may have a role in BCL-6-associated
      lymphomas.

PMID- 10898797
TI  - The alpha4 isoform of the Na,K-ATPase is expressed in the germ cells of the
      testes.
AB  - In addition to the three isoforms of the catalytic subunit of the Na, K-ATPase
      originally identified (alpha1, alpha2, and alpha3), a fourth alpha polypeptide
      (alpha4) has recently been found in mammalian cells. This novel alpha-subunit of
      the Na,K-ATPase is selectively expressed in male gonadal tissues. In the testes,
      alpha4 is functionally active and comprises approximately half of the Na, K
      ATPase activity of the organ. At present, the pattern of expression of the alpha4
      polypeptide within the cells of the male gonad is unknown. By in situ
      hybridization, immunocytochemistry, and the ouabain inhibition profile of Na,K
      ATPase activity, we show that the alpha4-subunit is expressed in the germ cells
      of rat testes. The highest amounts of the isoform are found in spermatozoa, where
      it constitutes two thirds of the Na,K-ATPase activity of the gametes. The other
      Na pump present in the cells is the ubiquitously expressed alpha1 polypeptide.
      The characteristic localization of alpha4 in the gonad is further supported by
      the drastic reduction of the polypeptide in mice that are infertile as a
      consequence of arrest in maturation of the germ cells. In addition, GC-1spg
      cells, a murine cell line derived from testis spermatogonia, also contain the Na,
      K-ATPase alpha4 polypeptide. However, the level of expression of the isoform in
      these cells is much lower than in the spermatozoa, a fact that may depend on the
      limited ability of the GC-1spg cells to differentiate in vitro. The particular
      expression of the Na,K-ATPase alpha4 isoform we encounter and the specific
      enzymatic properties of the polypeptide suggests its importance for ionic
      homeostasis of the germ cells of the testes.

PMID- 10898798
TI  - Age-related alterations in IL-1beta, TNF-alpha, and IL-6 concentrations in
      parotid acinar cells from BALB/c and non-obese diabetic mice.
AB  - IL-1beta, TNF-alpha, and IL-6 have been implicated in the destruction of parotid
      gland acinar cells (but not duct cells) in autoimmune sialoadenitis. Here we
      report the temporal alterations of these cytokines in parotid acinar cells that
      may lead to this specificity in cell death in the non-obese diabetic (NOD) mouse
      model for Sjogren's syndrome. Immunohistochemistry on paraffin sections of
      parotid gland from 5- and 10-week-old BALB/c and NOD mice confirmed the presence
      of many peri-acinar lymphoid nodules but few T-cells and macrophages between
      acinar cells. RT-PCR on enzymatically dispersed mouse parotid acinar cells
      (MPACs) showed no bands for CD3varepsilon, CD20, or F4/80 regardless of mouse
      strain or age. By ELISA, MPACs from 10-week-old NODs showed a small but highly
      significant (p<0.003) increase in IL-1beta and a large significant decrease
      (p<0.008) in IL-6 compared to 5-week-old NODs. Norepinephrine-stimulated amylase
      release from MPACs was not different regardless of mouse strain or age. These
      data show that alterations in acinar cell production of IL-1beta and IL-6 in
      aging NODs precede periductal lymphoid aggregates and acinar cell secretory
      dysfunction. (J Histochem Cytochem 48:1033-1041,2000)

PMID- 10898799
TI  - Morphological and immunocytochemical analyses on the effects of diet-induced
      hypocalcemia on enamel maturation in the rat incisor.
AB  - During the maturation stage of amelogenesis, the loss of matrix proteins combined
      with an accentuated but regulated influx of calcium and phosphate ions into the
      enamel layer results in the "hardest" tissue of the body. The aim of the present
      investigation was to examine the effects of chronic hypocalcemia on the
      maturation of enamel. Twenty-one-day old male Wistar rats were given a calcium
      free diet and deionized water for 28 days, while control animals received a
      normal chow. The rats were perfused with aldehyde and the mandibular incisors
      were processed for histochemical and ultrastructural analyses and for
      postembedding colloidal gold immunolabeling with antibodies to amelogenin,
      ameloblastin, and albumin. The maturation stage enamel organ in hypocalcemic rats
      exhibited areas with an apparent increase in cell number and the presence of cyst
      like structures. In both cases the cells expressed signals for ameloblastin and
      amelogenin. The content of the cysts was periodic acid-Schiff- and periodic acid
      silver nitrate-methanamine-positive and immunolabeled for amelogenin,
      ameloblastin, and albumin. Masses of a similar material were also found at the
      enamel surface in depressions of the ameloblast layer. In addition, there were
      accumulations of glycoproteinaceous matrix at the interface between ameloblasts
      and enamel. In decalcified specimens, the superficial portion of the enamel
      matrix sometimes exhibited the presence of tubular crystal "ghosts." The basal
      lamina, normally separating ameloblasts and enamel during the maturation stage,
      was missing in some areas. Enamel crystals extended within membrane invaginations
      at the apical surface of ameloblasts in these areas. Immunolabeling for
      amelogenin, ameloblastin, and albumin over enamel was variable and showed a
      heterogeneous distribution. In contrast, enamel in control rats exhibited a
      homogeneous labeling for amelogenin, a concentration of ameloblastin at the
      surface, and weak reactivity for albumin. These results suggest that diet-induced
      chronic hypocalcemia interferes with both cellular and extracellular events
      during enamel maturation.

PMID- 10898800
TI  - A histomorphometric, structural, and immunocytochemical study of the effects of
      diet-induced hypocalcemia on bone in growing rats.
AB  - Despite several studies on the effect of calcium deficiency on bone status, there
      is relatively little information on the ensuing histological alterations. To
      investigate bone changes during chronic hypocalcemia, weanling rats were kept on
      a calcium-free diet and deionized water for 28 days while control animals were
      fed normal chow. The epiphyseal-metaphyseal region of the tibiae were processed
      for histomorphometric, histochemical, and structural analyses. The distribution
      of bone sialoprotein (BSP), osteocalcin (OC), and osteopontin (OPN), three
      noncollagenous bone matrix proteins implicated in cell-matrix interactions and
      regulation of mineral deposition, was examined using postembedding colloidal gold
      immunocytochemistry. The experimental regimen resulted in serum calcium levels
      almost half those of control rats. Trabecular bone volume showed no change but
      osteoid exhibited a significant increase in all its variables. There were a
      multitude of mineralization foci in the widened osteoid seam, and intact matrix
      vesicles were observed in the forming bone. Many of the osteoblasts apposed to
      osteoid were tartrate-resistant acid phosphatase (TRAP)- and alkaline phosphatase
      positive, whereas controls showed few such TRAP-reactive cells. Osteoclasts in
      hypocalcemic rats generally exhibited poorly developed ruffled borders and were
      inconsistently apposed to bony surfaces showing a lamina limitans. Sometimes
      osteoclasts were in contact with osteoid, suggesting that they may resorb
      uncalcified matrix. Cement lines at the bone-calcified cartilage interface in
      some cases were thickened but generally did not appear affected at bone-bone
      interfaces. As in controls, electron-dense portions of the mineralized matrix
      showed labeling for BSP, OC, and OPN but, in contrast, there was an abundance of
      immunoreactive mineralization foci in osteoid of hypocalcemic rats. These data
      suggest that chronic hypocalcemia affects both bone formation and resorption.

PMID- 10898801
TI  - Gene expression patterns of the fibroblast growth factors and their receptors
      during myogenesis of rat satellite cells.
AB  - Satellite cells are the myogenic precursors in postnatal muscle and are situated
      beneath the myofiber basement membrane. We previously showed that fibroblast
      growth factor 2 (FGF2, basic FGF) stimulates a greater number of satellite cells
      to enter the cell cycle but does not modify the overall schedule of a short
      proliferative phase and a rapid transition to the differentiated state as the
      satellite cells undergo myogenesis in isolated myofibers. In this study we
      investigated whether other members of the FGF family can maintain the
      proliferative state of the satellite cells in rat myofiber cultures. We show that
      FGF1, FGF4, and FGF6 (as well as hepatocyte growth factor, HGF) enhance satellite
      cell proliferation to a similar degree as that seen with FGF2, whereas FGF5 and
      FGF7 are ineffective. None of the growth factors prolongs the proliferative phase
      or delays the transition of the satellite cells to the differentiating,
      myogenin(+) state. However, FGF6 retards the rapid exit of the cells from the
      myogenin(+) state that routinely occurs in myofiber cultures. To determine which
      of the above growth factors might be involved in regulating satellite cells in
      vivo, we examined their mRNA expression patterns in cultured rat myofibers using
      RT-PCR. The expression of all growth factors, excluding FGF4, was confirmed. Only
      FGF6 was expressed at a higher level in the isolated myofibers and not in the
      connective tissue cells surrounding the myofibers or in satellite cells
      dissociated away from the muscle. By Western blot analysis, we also demonstrated
      the presence of FGF6 protein in the skeletal musle tissue. Our studies therefore
      suggest that the myofibers serve as the main source for the muscle FGF6 in vivo.
      We also used RT-PCR to analyze the expression patterns of the four tyrosine
      kinase FGF receptors (FGFR1-FGFR4) and of the HGF receptor (c-met) in the
      myofiber cultures. Depending on the time in culture, expression of all receptors
      was detected, with FGFR2 and FGFR3 expressed only at a low level. Only FGFR4 was
      expressed at a higher level in the myofibers but not the connective tissue cell
      cultures. FGFR4 was also expressed at a higher level in satellite cells compared
      to the nonmyogenic cells when the two cell populations were released from the
      muscle tissue and fractionated by Percoll density centrifugation. The unique
      localization patterns of FGF6 and FGFR4 may reflect specific roles for these
      members of the FGF signaling complex during myogenesis in adult skeletal muscle.

PMID- 10898802
TI  - COS cells expression cloning of tyrosine-phosphorylated proteins by
      immunocytochemistry.
AB  - Tyrosine phosphorylation is an important post-translational modification of
      proteins, essential in many aspects of the cell economy, particularly in signal
      transduction pathways. Despite the importance of protein tyrosine
      phosphorylation, the approaches available for molecular cloning remain limited.
      We have developed a COS cell-based eukaryotic expression cloning procedure for
      phosphotyrosine-containing proteins by immunocytochemistry of cell monolayers.
      The approach takes advantage of the low basal levels of tyrosine phosphorylated,
      robust transient expression, availability of specific antibodies against tyrosine
      phosphorylated residues, and rescue of episomal DNA after immunocytochemistry.
      The technique is validated by cloning the rat proto-oncogene c-fgr in its
      tyrosine-phosphorylated form out of a rat kidney cDNA library containing over
      10(6) primary recombinants. This technique set the grounds for expression cloning
      of tyrosine-phosphorylated proteins in eukaryotic cells, and it is anticipated
      that further modifications and refinements will allow the identification of
      protein tyrosine phosphatase substrates.

PMID- 10898803
TI  - Glioma-associated antigen expression in oligodendroglial neoplasms. Tenascin and
      epidermal growth factor receptor.
AB  - Epidermal growth factor receptor (EGFR), its variant, EGFRvIII, and tenascin are
      glioma-associated antigens that are hyperexpressed by neoplastic glial cells
      relative to normal brain, making them attractive antigenic targets for
      immunotherapy. Preliminary surveys indicate that oligodendroglial tumors also
      produce these proteins, although the exact patterns and degrees of reactivity are
      not known. In this study we examined the immunoreactivity of tenascin among 50
      oligodendroglial tumors, including 25 well-differentiated oligodendrogliomas
      (WDOs) and 12 glioblastomas (GBMs) exhibiting high proportions of oligodendroglia
      like cells. We used well-characterized immunoreagents with defined specificities
      against the target antigens on formalin-fixed, paraffin-embedded archival tissue.
      The tumors were graded according to WHO guidelines. Immunoreactivity was reported
      on a 1-3 scale according to staining intensity multiplied by a 1-3 distribution
      scale distribution within tumor as focal (1), multifocal (2), and diffuse (3) for
      both the parenchymal and the perivascular components. Although there is
      considerable overlap in antigen production among the grades of tumor, this study
      establishes the production of tenascin and wild-type EGFR (but not EGFR vIII) in
      oligodendroglial neoplasms and supports the concept that antigen production
      increases with tumor grade.

PMID- 10898804
TI  - Expression of neuronal nitric oxide synthase in several cell types of the rat
      gastric epithelium.
AB  - The aim of this study was to identify which cell types of the rat gastric
      epithelium express neuronal nitric oxide synthase (nNOS) because the results of
      the previous studies have been very divergent regarding this point. By the
      combination of immunohistochemical (IHC) and in situ hybridization (ISH)
      techniques, we detected expression of nNOS in chief and mucosecretory cells of
      the gastric epithelium. Moreover, some gastric endocrine cells were
      immunoreactive for nNOS, although they could not be distinguished in sections
      treated with ISH techniques. The strongest signal for all antibodies in IHC
      techniques was obtained when microwave (MW) heating was performed before the IHC
      procedure. Our results indicate that in the gastric epithelium a variety of cell
      types are able to produce NO. The NO produced by the different cell types (chief,
      mucous, and endocrine) may form a complex network of paracrine communication with
      an important role in gastric physiology.

PMID- 10898806
TI  - Cathepsin A is expressed in a cell- and region-specific manner in the testis and
      epididymis and is not regulated by testicular or pituitary factors.
AB  - The epithelial cells of the testis are involved in the production,
      differentiation, and sustenance of sperm, and those of the epididymis play a
      major role in sperm maturation, protection, and storage. These tissues express
      various proteins that respond differently to androgens. Cathepsin A is a
      multifunctional lysosomal carboxypeptidase that also functions as a protective
      and an activator protein for neuraminidase and beta-galactosidase. In this study,
      cathepsin A was immunolocalized by light and electron microscopy using a
      polyclonal affinity-purified antibody on the testis and epididymis of normal,
      orchidectomized with or without testosterone supplementation, efferent duct
      ligated, and hypophysectomized adult rats. In normal rats, cathepsin A expression
      was noted in lysosomes of Sertoli and Leydig cells but not in germ cells of the
      testis, as well as nonciliated cells of the efferent ducts. In the epididymis, a
      cell- and region-specific distribution of cathepsin A was noted. In
      experimentally treated animals, no changes were noted in the expression of
      cathepsin A. Immunolabeling of tissues examined at the electron microscopic level
      revealed that lysosomes were reactive. These data indicate cell- and region
      specific expression of cathepsin A in cells of the testis and epididymis and also
      indicate that cathepsin A expression is not regulated by testicular or pituitary
      factors.

PMID- 10898805
TI  - Immunohistochemical localization of protein gene product 9.5, ubiquitin, and
      neuropeptide Y immunoreactivities in epithelial and neuroendocrine cells from
      normal and hyperplastic human prostate.
AB  - This study was designed to investigate (a) the presence of protein gene product
      9.5 (PGP 9.5), ubiquitin, and neuropeptide Y (NPY) in the neuroendocrine and
      secretory epithelium of the human normal prostate and its secretions, and (b) the
      changes in immunoreactivity to these proteins in men with benign prostatic
      hyperplasia. Western blotting and light microscopic immunohistochemistry
      techniques were used and the numerical density of immunoreactive neuroendocrine
      cells, and the volume fractions of immunostained secretory epithelium were
      evaluated. Western blotting revealed the presence of the three antigens in both
      tissue homogenates and prostate secretion. Some neuroendocrine cells
      immunoreacted to PGP 9.5 and NPY in all the prostate regions of control
      specimens. Ubiquitin immunoreactivity was detected in the nuclei from both basal
      cells and secretory epithelial cells. The cytoplasm of the secretory cells and
      the glandular lumen also showed immunostaining for the three proteins. The
      numerical densities of both PGP 9.5 and NPY neuroendocrine cells were lower in
      hyperplasia than in controls. No differences in the volume fraction occupied by
      epithelial immunostaining to both proteins was found between hyperplastic and
      control prostates. We concluded that (a) PGP 9.5 and NPY, but not ubiquitin, are
      common antigens in both neuroendocrine and secretory prostate cells, (b) the
      three immunoreactive proteins contribute to the prostate secretions, and (c) the
      secretion of ubiquitin is markedly diminished in the hyperplastic epithelium.(J
      Histochem Cytochem 48:1121-1130, 2000)

PMID- 10898807
TI  - Subcellular localization of leptin in non-tumorous and adenomatous human
      pituitaries: an immuno-ultrastructural study.
AB  - Leptin is a key mediator in the maintenance of neuroendocrine homeostasis.
      Recently, leptin and leptin receptor expression were demonstrated in non-tumorous
      and adenomatous human pituitaries. This study was performed to determine the
      subcellular localization of leptin in human adenohypophyses (n = 3) and in
      various types of pituitary adenoma (n = 16). Immunoelectron microscopy showed
      leptin immunolabeling in most hormone-producing cells of the human non-tumorous
      adenohypophysis, but not in stellate cells. Labeling was noted over secretory
      granules. Immunocytochemistry using double labeling revealed leptin expression in
      GH-, ACTH-, TSH-, and FSH/LH-containing cells but not in PRL cells. The
      percentage of immunopositive cells and the intensity of immunostaining varied
      considerably among the various cell types. Immunoelectron microscopy with double
      gold labeling showed co-localization of leptin and adenohypophysial hormones in
      the same secretory granules. Among pituitary tumors, leptin immunolabeling was
      evident only in corticotroph adenomas. Compared to non-tumorous corticotrophs,
      leptin immunoexpression was less abundant in corticotroph adenomas. The presence
      of leptin and adenohypophysial hormones in the same secretory granules suggests
      that leptin is secreted concomitantly with various adenohypophysial hormones and
      that its release is under the control of hypothalamic stimulating and inhibiting
      hormones.

PMID- 10898809
TI  - Celebrations in Pioneering Electron Microscopy: A Symposium in Honor of Professor
      Archie Howie-Introduction.

PMID- 10898808
TI  - Application of microwave technology to the processing and immunolabeling of
      plastic-embedded and cryosections.
AB  - We have adapted existing microwave irradiation (MWI) protocols and applied them
      to the processing and immunoelectron microscopy of both plastic-embedded and
      frozen sections. Rat livers were fixed by rapid MW irradiation in a mild fixation
      solution. Fixed liver tissue was either cryosectioned or dehydrated and embedded
      in Spurr's, Unicryl, or LR White resin. Frozen sections and sections of acrylic
      embedded tissue were immunolabeled in the MW oven with an anti-catalase antibody,
      followed by gold labeling. Controls were processed conventionally at room
      temperature (RT). The use of MWI greatly shortened the fixation, processing, and
      immunolabeling times without compromising the quality of ultrastructural
      preservation and the specificity of labeling. The higher immunogold labeling
      intensity was achieved after a 15-min incubation of primary antibody and gold
      markers under discontinued MWI at 37C. Quantification of the immunolabeling for
      catalase indicated a density increase of up to fourfold in the sections
      immunolabeled in the MW oven over that of samples immunolabeled at RT. These
      studies define the general conditions of fixation and immunolabeling for both
      acrylic resin-embedded material and frozen sections.

PMID- 10898810
TI  - Extended and Point Defects in Diamond Studied with the Aid of Various Forms of
      Microscopy.
AB  - It is shown that star disclinations can be a significant source of stress in
      chemical vapor deposited (CVD) diamond. This purely geometrical origin contrasts
      with other sources of stress that have been proposed previously. The
      effectiveness is demonstrated of the use of electron irradiation using a
      transmission electron microscope (TEM) to displace atoms from their equilibrium
      sites to investigate intrinsic defects and impurities in CVD diamond. After
      irradiation, the samples are studied by low temperature photoluminescence
      microscopy using UV or blue laser illumination. Results are given that are
      interpreted as arising from isolated <100> split self-interstitials and
      positively charged single vacancies. Negatively charged single vacancies can also
      be revealed by this technique. Nitrogen and boron impurities may also be studied
      similarly. In addition, a newly developed liquid gallium source scanned ion beam
      mass spectrometry (SIMS) instrument has been used to map out the B distribution
      in B doped CVD diamond specimens. The results are supported by micro-Raman
      spectroscopy.

PMID- 10898811
TI  - Threshold Energy Effects in Secondary Electron Emission.
AB  - In large bandgap semiconductors and insulators, the threshold energies for e-h
      pair production and ionization damage can lie above the vacuum level. For low
      energy imaging, a window is then opened whose width is potentially sensitive to
      local changes in work function, doping level, or acidity. Recent progress and
      future opportunities for damage-free imaging of these properties using low energy
      electrons are discussed in the light of the underlying physics, as well as of
      recent instrumental developments in low energy electron microscopy (LEEM),
      environmental scanning electron microscopy (ESEM), photoelectron emission
      microscopy (PEEM), scanned probe microscopy (SPM), and projection electron
      microscopy.

PMID- 10898812
TI  - Insights into the Electronic Structure of Ceramics through Quantitative Analysis
      of Valence Electron Energy-loss Spectroscopy.
AB  - Valence electron energy-loss (VEEL) spectroscopy was performed on six ceramic
      materials in a dedicated scanning transmission electron microscope (STEM).
      Quantitative analysis of these data is described yielding access to the complex
      optical properties and the electronic structure of the materials. Comparisons are
      made on the basis of the interband transition strength describing transitions
      between occupied states in the valence band and empty states in the conduction
      band. This proves that the quantitative analysis of VEEL data is a competitive
      and complementary method to be considered when investigating the electronic
      structure of materials. Possibilities for improvement and extension of the
      analysis are discussed extensively.

PMID- 10898813
TI  - On Low Voltage Scanning Electron Microscopy and Chemical Microanalysis.
AB  - The current status and general applicability of scanning electron microscopy
      (SEM) at low voltages is reviewed for both imaging (low voltage scanning electron
      microscopy, LVSEM) and chemical microanalysis (low voltage energy-dispersive X
      ray spectrometry, LVEDX). With improved instrument performance low beam energies
      continue to have the expected advantages for the secondary electron imaging of
      low atomic number (Z) and electrically non-conducting samples. They also provide
      general improvements in the veracity of surface topographic analysis with
      conducting samples of all Z and at both low and high magnifications. In new
      experiments the backscattered electron (BSE) signal retains monotonic Z
      dependence to low voltages (<1 kV). This is contrary to long standing results in
      the prior literature and opens up fast chemical mapping with low dose and very
      high (nm-scale) spatial resolution. Similarly, energy-dispersive X-ray chemical
      microanalysis of bulk samples is extended to submicron, and in some cases to <0.1
      um, spatial resolution in three dimensions at voltages <5 kV. In favorable cases,
      such as the analysis of carbon overlayers at 1.5 kV, the thickness sensitivity
      for surface layers is extended to <2 nm, but the integrity of the sample surface
      is then of concern. At low beam energies (E(0)) the penetration range into the
      sample, and hence the X-ray escape path length out of it, is systematically
      restricted (R = F(E(0)(5/3))), with advantages for the accuracy or elimination of
      complex analysis-by-analysis matrix corrections for absorption (A) and
      fluorescence (F). The Z terms become more sensitive to E(0) but they require only
      one-time calibrations for each element. The new approach is to make the physics
      of the beam-specimen interactions the primary factor and to design enabling
      instrumentation accordingly.

PMID- 10898814
TI  - Inferring Physical Parameters from Images of Vibrating Carbon Nanotubes.
AB  - We describe a hidden parameter inferencing algorithm for deducing the length,
      width, and vibration profile from images of thermally excited single-wall carbon
      nanotubes. With accurate estimates of these parameters, the Young's modulus can
      be deduced. The algorithm is sensitive to shot noise in the image, primarily
      because of the low nanotube image contrast. Noise causes the nanotube length and
      width to be overestimated, and the vibration amplitude to be underestimated.
      After correcting for shot noise, we infer an average value of the Young's modulus
      of <Y> = 1.20 +/- 0.20 TPa, which is larger than the currently accepted value for
      graphite.

PMID- 10898815
TI  - Microscopy of Metal Oxide Surfaces.
AB  - Elevated temperature scanning tunneling microscopy is used to study oxides that
      are room temperature insulators but become sufficiently electrically conducting
      at higher temperatures to allow imaging to be performed. Atomic resolution images
      of NiO, CoO, and UO(2) have been obtained in this fashion which allow surface
      structure and defect determination. To complement the experiments, modeling of
      the electronic surface structure reveals which atomic sites give rise to the
      contrast observed in the images. Low voltage scanning electron microscopy is used
      to image small equilibrium pores in UO(2) single crystals to evaluate the surface
      energy ratio of the (111) to (001) surfaces.

PMID- 10898816
TI  - Characterization of Amorphous Materials by Electron Diffraction and Atomistic
      Modeling.
AB  - The technique of energy selected electron diffraction gives information about
      amorphous structures which can be used to characterize amorphous materials in
      terms of their structure. The diffraction data can be used to refine models
      obtained using molecular dynamics, resulting in physically reasonable models
      consistent with the diffraction data.

PMID- 10898817
TI  - In Situ Real-time Environmental High Resolution Electron Microscopy of Nanometer
      Size Novel Xerogel Catalysts for Hydrogenation Reactions in Nylon 6,6.
AB  - In situ real-time environmental high resolution electron microscopy (EHREM) under
      controlled reaction environments permits direct atomic resolution imaging of
      dynamic surface and sub-surface microstructures of reacting catalysts. Using the
      EHREM and complementary microscopy methods, we have investigated selective
      hydrogenation reaction mechanisms over novel xerogel catalysts of ruthenium and
      Ru with Co and Au promoters on titania supports, and report an alternative
      heterogeneous catalytic process for the hydrogenation of adiponitrile (ADN) in
      the manufacture of Nylon 6,6. The direct EHREM observations are supported by
      ultra-high resolution low voltage scanning electron microscope (SEM) of spatial
      distributions of the highly dispersed nanometer-size catalyst particles and
      parallel chemical studies. The results demonstrate the important role of in situ
      EHREM in the design of heterogeneous catalytic hydrogenation processes on the
      nanoscale.

PMID- 10898818
TI  - Z-contrast Imaging in an Aberration-corrected Scanning Transmission Electron
      Microscope.
AB  - We show that in the limit of a large objective (probe-forming) aperture, relevant
      to a spherical aberration corrected microscope, the Z-contrast image of a zone
      axis crystal becomes an image of the 1s Bloch states. The limiting resolution is
      therefore the width of the Bloch states, which may be greater than that of the
      free probe. Nevertheless, enormous gains in image quality are expected from the
      improved contrast and signal-to-noise ratio. We present an analytical channeling
      model for the thickness dependence of the Z-contrast image in a zone-axis
      crystal, and show that, at large thicknesses, columnar intensities become
      proportional to the mean square atomic number, Z(2).

PMID- 10898819
TI  - Rapid and Semi-automated Method for Analysis of the Number of Atoms of Ultra
      small Platinum Clusters on Carbon.
AB  - Very high angle ( approximately 100 mrad) annular dark-field (HAADF) images in a
      dedicated scanning transmission electron microscope (STEM) can be used to
      quantitatively measure the number of atoms in a cluster on a support material. We
      have developed a computer program which will automatically find the location of
      the particles and then integrate the intensity to find the number of atoms per
      cluster. We have examined ultra-small Pt clusters on a C substrate by this novel
      mass-spectroscopic technique. We discovered that the Pt clusters maintain their
      three-dimensional shape, and are probably spherical.

PMID- 10898820
TI  - Direct Observation of the Atomic Structure in a Solid-Liquid Interface.
AB  - An experimental high-resolution image of a solid-liquid interface of solid Si and
      liquid Al-Si alloy has been compared with theoretical images obtained by computer
      simulation. It has been concluded that the solid-liquid interface has a
      transition layer, the structure of which is compatible with the 1 x 1 Si-{111}
      surface.

PMID- 10898821
TI  - Annihilation Behaviors of Athermal omega-Phase Crystals Due to Electron
      Irradiation.
AB  - Annihilation behaviors of athermal omega-phase crystals formed by cooling at 131
      K for 10.8 ks under four different electron irradiation conditions of
      acceleration voltages of 200 kV and 160 kV, and beam currents of approximately 20
      pA/cm(2) and 5 pA/cm(2) were investigated using in situ dark field and HREM
      observation methods at 131 K. The effect of acceleration voltages on the
      lifetimes is recognized, i.e., in the case of approximately equal electron beam
      current, lifetimes at 200 kV become shorter than those at 160 kV. Also, lifetimes
      depend on the electron beam current at 200 kV, i.e., the higher the beam
      currents, the shorter the lifetimes become. However, no distinct dependence can
      be seen at 160 kV. Since annihilations of athermal omega-phase crystals begin
      after the electron irradiation for a certain period in each condition, which
      depends on acceleration voltages and beam currents, it is suggested that the
      annihilation behaviors have incubation periods.

PMID- 10898822
TI  - Transmission Electron Diffraction at 200 eV and Damage Thresholds below the
      Carbon K Edge.
AB  - Transmission electron diffraction patterns from ultra-thin aromatic and aliphatic
      organic films at beam energies of 200 eV-1 keV have been recorded in a custom low
      energy electron transmission (LEET) chamber. A significant reduction of the
      molecular damage cross-section, measured by fading of diffraction spots, was
      found for thin films of the aromatic perylene when the beam energy was reduced
      from 400 to 200 eV. The corresponding measurements for the aliphatic tetracontane
      showed a smaller "threshold energy" and the differences are discussed. Electron
      beam damage from other aromatic materials has also been studied at low energy.
      Comparison of the carbon K shell ionization cross-section and the measured damage
      cross-sections show that carbon K-shell ionization is strongly correlated with
      the damage observed in aromatics at beam energies higher than 284 eV. Calculation
      of the minimum number of unit cells needed for imaging a single molecule, and
      comparison of calculated elastic with measured damage cross-sections both
      indicate new possibilities for imaging biomolecules with low energy electrons.

PMID- 10898823
TI  - Field Emission and Electron Microscopy.
AB  - An overview and new results are presented of the investigations carried out in
      the last 5 years on nano-sized tips by means of electron microscopy, an electron
      optical bench, and computation. Tungsten and, in particular, carbon nano-tips
      prepared by carbon contamination in a scanning electron microscope, were studied
      for applications as field-emission electron sources. Several features of their
      use are described and the results concerning the determination of some of their
      basic properties are reported.

PMID- 10898824
TI  - Contrast of Highly Dispersed Metal Nanoparticles in High-resolution Secondary
      Electron and Backscattered Electron Images of Supported Metal Catalysts.
AB  - Platinum nanoparticles finely dispersed in activated carbon powders have been
      observed with high contrast in secondary electron (SE) and backscattered electron
      (BE) images. The factors that contribute to the visibility of small metal
      particles in high-resolution BE and SE images are discussed. Monte Carlo
      simulations provided insight into the scattering of electrons by small, heavy
      element particles located on, or embedded in, light-element supports. The
      visibility of Pt nanoparticles in BE images depends on many factors including the
      size and the location of the Pt particles, the energy of the incident electrons,
      and the size of the electron probe. The SE signals generated by backscattered
      electrons may not significantly contribute to the visibility of small Pt
      particles in high-resolution SE images of carbon supported Pt catalysts. Only
      those small Pt particles that are located on or very close to the surface of the
      carbon support can be revealed in high-resolution SE images.

PMID- 10898826
TI  - News and Commentary.

PMID- 10898825
TI  - Electron Crystallography of Room Temperature Charge Ordering in Fe(3)O(4).
AB  - A previously unknown form of charge ordering has been observed in dislocation
      free thin films of magnetite, Fe(3)O(4). This charge ordering exists on
      tetrahedral sites and is unrelated to the well known low temperature ordering on
      octahedral sites that occurs below 120K. From modeling of electron diffraction
      patterns we deduce that the best fit to the observed diffraction patterns was
      obtained by reducing the scattering power on one tetrahedral site per unit cell
      by about 80%.

PMID- 10898827
TI  - Pharmacokinetics and safety of tazarotene.
AB  - The pharmacokinetic profile of tazarotene helps to ensure that systemic exposure
      to the drug and its metabolites is minimal. First, percutaneous penetration is
      limited, with less than 6% of the applied drug being absorbed into the
      bloodstream. Second, tazarotene is rapidly metabolized into tazarotenic acid and
      other metabolites that are not lipophilic. Third, tazarotene and its metabolites
      are rapidly eliminated from the blood in the urine and feces. These three
      pharmacokinetic features help to ensure that post-treatment plasma levels of
      tazarotene and its metabolites are comparable to those of endogenous retinoids,
      which suggests that the risk of teratogenic effects is minimal. Limited systemic
      exposure to the drug also ensures that any adverse effects are local effects
      rather than systemic effects. Overall, tazarotene has a good safety profile and
      is not associated with contact sensitization, phototoxicity, photoallergic
      reactions, mutagenicity, or carcinogenicity.

PMID- 10898828
TI  - Tazarotene combination treatments in psoriasis.
AB  - In the hope of increasing efficacy and improving safety, several combination
      regimens involving tazarotene gel have been explored for the treatment of plaque
      psoriasis. A number of large-scale studies have shown that the adjunctive use of
      a mid-potency or high-potency steroid can enhance both the efficacy and
      tolerability of tazarotene treatment. A small pilot study also suggested improved
      efficacy when used in combination with calcipotriene. Likewise, the adjunctive
      use of tazarotene can enhance the efficacy and potentially the safety of
      treatment with steroids, broad-band and narrow-band UVB phototherapy, and
      psoralens plus UVA bath therapy.

PMID- 10898829
TI  - Strategies to optimize efficacy, duration of remission, and safety in the
      treatment of plaque psoriasis by using tazarotene in combination with a
      corticosteroid.
AB  - In the treatment of plaque psoriasis with corticosteroids, long-term efficacy and
      safety are often compromised by tachyphylaxis, steroid rebound, and adverse
      effects. However, the results of recent studies demonstrate that the use of
      tazarotene in conjunction with a corticosteroid can help to optimize the
      efficacy, the duration of remission, and the safety of corticosteroid treatment.
      In one study, the adjunctive use of tazarotene with a mid-potency corticosteroid
      promoted greater efficacy, more rapid efficacy, and more prolonged remission
      after treatment than corticosteroid monotherapy. In another study, after the
      induction of remission with tazarotene plus a superpotent corticosteroid,
      maintenance therapy with tazarotene, with or without the superpotent
      corticosteroid, achieved more sustained remissions than vehicle. In a third
      study, tazarotene reduced the degree of epidermal atrophy induced by repeated
      applications of a superpotent corticosteroid on normal skin in healthy
      volunteers.

PMID- 10898830
TI  - Combination azelaic acid therapy for acne vulgaris.
AB  - There is no topical antiacne medication that acts against all four of the major
      pathophysiologic features of acne: hyperkeratinization, sebum production,
      bacterial proliferation, and inflammation. Topical azelaic acid cream helps both
      to normalize keratinization and to reduce the proliferation of Propionibacterium
      acnes, and has proven to be effective against both noninflammatory and
      inflammatory lesions. The results of a recent study now demonstrate that its
      efficacy can be enhanced, and patient ratings of overall impression improved,
      when it is used in combination with other topical medications such as benzoyl
      peroxide 4% gel, clindamycin 1% gel, tretinoin 0.025% cream, and erythromycin
      3%/benzoyl peroxide 5% gel. Furthermore, another study has shown that azelaic
      acid plus benzoyl peroxide achieves greater efficacy and higher patient ratings
      of convenience than monotherapy with erythromycin-benzoyl peroxide gel.

PMID- 10898832
TI  - In memoriam-I. Kenneth adisman, DDS, MS

PMID- 10898831
TI  - Tazarotene versus tretinoin or adapalene in the treatment of acne vulgaris.
AB  - The efficacy and tolerability of tazarotene 0.1% gel in the treatment of acne
      vulgaris have been compared with those of tretinoin 0.025% gel and adapalene 0.1%
      gel in multicenter, double-blind, randomized, parallel-group trials. Preliminary
      results from the tazarotene versus tretinoin trial suggest that once-daily
      tazarotene is more efficacious than once-daily tretinoin in reducing the numbers
      of papules and open comedones, and achieves a more rapid reduction in pustules.
      Both drugs appear to be equally efficacious against closed comedones. Preliminary
      results from the tazarotene versus adapalene trial suggest that, when tazarotene
      is applied only half as frequently as adapalene (every other day versus every
      day), the two drugs achieve comparable reductions in noninflammatory and
      inflammatory lesion counts. The results from these studies, and a separate split
      face tolerability study, suggest that the tolerability of tazarotene gel is
      clinically comparable to that of tretinoin 0.025% gel, tretinoin 0.1% gel
      microsphere, and adapalene 0.1% gel.

PMID- 10898834
TI  - The israel society of oral rehabilitation-founded in 1968

PMID- 10898833
TI  - Turkish prosthodontics and implantology association-founded in 1976

PMID- 10898835
TI  - How to evaluate a dental article about harm.

PMID- 10898836
TI  - The overview: an article that interrogates the literature.
AB  - Although the question on the efficacy of chlorhexidine therapy for the
      clinician's adult patient may not have been totally answered, a greater
      perspective on this treatment modality was gained by the reader because of the
      quality of the overview cited, and the evidence-based approach used by the
      authors in performing the overview.

PMID- 10898837
TI  - Magnetically connected removable sectional denture for a maxillary defect with
      severe undercut: a clinical report.
AB  - A removable sectional denture connected by a cobalt-samarium magnetic retention
      system ( Hicorex for a patient with a severe maxillary defect was described.
      After an observation period of 5 years, the obturator continues to function, with
      no deleterious effects resulting from the use of prosthetic components. This
      magnetic retention system is considered to be clinically useful for interrelating
      and retaining a sectional prosthesis parts.

PMID- 10898838
TI  - Dimensional accuracy of castings produced with ringless and metal ring investment
      systems.
AB  - STATEMENT OF PROBLEM: The ringless casting procedure is in use in clinical
      dentistry, although there is no adequate scientific data to support its use.
      PURPOSE: This study compared the vertical margin accuracy of lost wax castings
      produced with the conventional casting technique using a metal ring and a
      technique that uses a ringless system. MATERIAL AND METHODS: From copings
      fabricated on a metal die, 30 castings were produced from a high palladium alloy
      for metal ceramic restorations (Argedent). Ten castings were cast with Bellavest
      T (Bego) phosphate-bonded investment with the ringless technique, 10 were cast
      with the same investment with a metal ring, and the final 10 were cast using Hi
      temp (Whip Mix) phosphate-bonded investment with a metal ring. The internal
      surface of the castings were not modified before seating with finger pressure.
      For vertical margin discrepancy measurements, an optical microscope at a
      magnification of 100x was used. Data were analyzed with 1-way multivariate ANOVA
      (repeated measures) and the Student-Newman-Keuls test. RESULTS: When following
      the manufacturers' recommendations, the castings of the ringless technique
      provided less vertical margin discrepancy (mean value 181 +/- 71 microm) than the
      castings produced with the conventional metal ring technique (290 +/- 87 microm
      and 291 +/- 88 microm). The difference was significant (P <. 001). CONCLUSION:
      The ringless technique may produce accurate castings for use in fixed
      prosthodontics, therefore further investigation is needed to develop a protocol
      for its use.

PMID- 10898839
TI  - Effect of ring liner and casting ring temperature on the dimension of cast posts.
AB  - STATEMENT OF PROBLEM: If a post does not fit passively, binding with the
      radicular tooth structure occurs, possibly increasing the risk for root fracture.
      Therefore, it is necessary to fabricate slightly undersized cast posts to allow
      for passive fit and cement placement. Shrinkage of the mold cavity may be a
      desired effect during the casting of posts. PURPOSE: This study evaluated the
      influence of: (1) a cellulose ring liner, and (2) a lower casting temperature of
      the metal ring, on the dimensions of a cast post. MATERIAL AND METHODS: Eighty
      plastic posts were divided in 4 equal groups (group 1, 815 degrees C, liner;
      group 2, 815 degrees C, no liner; group 3, 600 degrees C, liner; and group 4, 600
      degrees C, no liner), invested in phosphate-bonded investment and cast with a
      noble alloy. Posts were measured at 2 locations, the tip and base, before and
      after casting. RESULTS: Investing in a lined metal ring and using a casting ring
      temperature of 815 degrees C (group 1) resulted in markedly oversized posts (tip:
      +25.8 microm; base: +20.3 microm). The absence of the cellulose liner in the
      casting ring (group 2) decreased the expansion of the investment producing
      slightly oversized castings (tip: +9.75 microm; base: +4.52 microm). Lined rings
      that were heated to a final temperature of 600 degrees C (group 3) produced posts
      that were oversized (tip: +16.65 microm; base: +11.05 microm). Final casting ring
      temperature of 600 degrees C and the absence of a cellulose liner (group 4)
      resulted in posts slightly undersized (tip: -4.1 microm; base: -2.2 microm).
      CONCLUSION: The use of 2 casting ring temperatures (815 degrees C or 600 degrees
      C) and the influence of a ring liner were investigated. Decreasing the casting
      ring temperature from 815 degrees C to 600 degrees C and the absence of a ring
      liner significantly decreased the dimensions of a cast post.

PMID- 10898840
TI  - Torsional resistance of crowns cemented to composite cores involving three
      stainless steel endodontic post designs.
AB  - STATEMENT OF PROBLEM: There are no studies analyzing the effects of a crown in
      relationship to torsional resistance for a titanium-reinforced core material
      supported by a post. PURPOSE: This study investigated the effects of post design
      on the torsional resistance of a crown supported by a titanium-reinforced
      composite core material (Ti-Core) and 3 endodontic posts (AccessPost, Flexi-Post,
      and ParaPost). MATERIAL AND METHOD: Three groups of 10 specimens per group were
      studied. A total of 30 recently extracted human single-rooted (incisors) teeth
      with their crowns removed were used. Post holes preparations were created
      according to manufacturer's instructions. All posts were cemented using Flexi
      Flow with titanium cement. Scotchbond Multi-Purpose bonding system was used as
      the bonding system for all groups. All cores were fabricated with Ti-Core with
      titanium core material with hard copper bands as the matrix. The Ti-Core core
      material was allowed to set for 1 hour. Metal crowns were fabricated and cemented
      with zinc phosphate cement. Specimens were placed in a special jig and a
      clockwise torsional force was applied. Torsional force was measured on a Lebow
      1102-200 torque transducer and recorded on a Hewlett Packard 7015B X-Y recorder
      in inch x ounce. A 1-way analysis of variance (ANOVA) was used to test for
      statistical significance (P < .001). RESULTS: The torsional values (inch x ounce)
      were AccessPost 77.2 +/- 30.3, Flexi-Post 162.2 +/- 51.2, and ParaPost 60.9 +/-
      28.4. SNK and Scheffe comparison tests revealed that the Flexi-Post group had
      significantly greater resistance to torque loading than the AccessPost and
      ParaPost groups, which were statistically similar to each other. CONCLUSION: Post
      design has an effect on torsional resistance of a crown supported by titanium
      reinforced core build-up and post. The threaded split-shank design of the Flexi
      Post dowel offers significantly greater resistance to torsional loading than the
      passive posts studied.

PMID- 10898841
TI  - Changes in the edentulous maxilla in persons wearing implant-retained mandibular
      overdentures.
AB  - STATEMENT OF PROBLEM: It has been suggested that risk for severe resorption in
      the anterior maxilla is increased in persons wearing mandibular implant-retained
      overdentures. However, little information is available about the changes in the
      edentulous maxilla after mandibular implant treatment. PURPOSE: This study
      determined the possible changes in the width of the maxillary residual ridge 6
      years after receiving mandibular implant-supported or implant-mucosa-supported
      overdentures and evaluated the association between the anatomic changes and
      subjective complaints with maxillary complete dentures. METHODS AND MATERIAL: The
      subjects for this study (n = 55), enrolled among the participants of a
      prospective clinical trial, were randomly assigned into 3 groups treated with:
      (a) implant-supported overdentures on a transmandibular implant system (n = 21);
      (b) implant-mucosa-supported overdentures on 2 IMZ implants (n = 20); or (c)
      conventional complete dentures (n = 14). A lingual contact occlusion concept with
      anterior open bite was used for tooth arrangement in all subjects. Diagnostic
      casts were made at baseline, and again at the 6-year follow-up. Most prominent
      points perpendicular to the crest of residual ridge were located in the incisor,
      canine, and premolar regions, after which the width of the ridge was recorded at
      these points with a Boley gage. Subjects' opinions on their dentures were
      evaluated with a questionnaire. RESULTS: Significant reduction in the width of
      the ridge was found in all measurement areas (mean difference = 0.4 to 0.6 mm; P
      <.0001). However, changes were small and not associated with the type of
      prosthetic restoration in the mandible. In subjects with implant-mucosa-supported
      overdentures, complaint of loose maxillary denture correlated with the decrement
      of residual ridge width. CONCLUSION: The width of residual ridge decreases with
      time, despite the type of mandibular prosthetic restoration.

PMID- 10898842
TI  - Clinical evaluation of single-tooth mini-implant restorations: a five-year
      retrospective study.
AB  - STATEMENT OF PROBLEM: Placement of small diameter implants often provides a
      solution to space problems in implant restoration. Analysis of the success of
      this type of implant restoration has not been clearly determined. PURPOSE: This 5
      year retrospective study presents results from 52 mini-implants for single-tooth
      restorations placed in 44 patients from 1992 to 1994. MATERIAL AND METHODS:
      Dental records of 44 patients with 52 mini-implants placed during 1992-94 were
      reviewed. The implants were all placed by the same surgeon and the single-tooth
      custom screwed posts with cemented crowns were positioned on the implants by the
      same prosthodontist. RESULTS: The results achieved by the mini-implant
      rehabilitation were similar to those reported for standard single-tooth implant
      restoration. Total implant survival rate was 94.2%. Two implants were lost at
      second stage surgery, and another was lost after temporary loading. CONCLUSION:
      The results suggest that single-tooth mini-implant restoration can be a
      successful treatment alternative to solve both functional and esthetic problems.
      They may represent the preferred choice in cases where space problems limit the
      use of standard or wide diameter implants.

PMID- 10898843
TI  - Bilaminar dual-purpose stent for placement of dental implants.
AB  - Proper placement of implants in the posterior maxillary region with poor bone
      density is essential to obtain long-term success. In this article, the
      fabrication of a bilaminar dual-purpose stent that facilitates ease in implant
      placement with improved verification of implant positioning is described. The
      outer lamina is designed for use in the computed tomography evaluation, using
      radiopaque markers. The verification of implant alignment and positioning,
      according to the determined prosthesis, is also performed with this template
      after modifying it for surgery. The inner lamina is designed to accept 2
      removable surgical acrylic resin stents with different guide channels that avoids
      the risk of surgical malpractice.

PMID- 10898844
TI  - Annual review of selected dental literature: report of the Committee on
      Scientific Investigation of the American Academy of Restorative Dentistry.

PMID- 10898845
TI  - Wear and surface roughness of current prosthetic composites after
      toothbrush/dentifrice abrasion.
AB  - STATEMENT OF PROBLEM: Surface changes of prosthetic composites caused by
      toothbrushing are known, although composite materials have been improved and are
      now widely used for various kinds of prosthetic restorations. PURPOSE: This study
      evaluated the influence of toothbrushing on abrasive wear and surface roughness
      of current prosthetic composites. MATERIAL AND METHODS: Seven composite materials
      (Artglass, Axis, Cesead II, Conquest Sculpture, Estenia, Infis, and Targis) were
      assessed, and a machinable ceramic material (Cerec 2 Vitablocs) was used as a
      reference. Composite specimens polymerized with their proprietary curing units
      and sectioned ceramic specimens were stored in water for 14 days, and
      subsequently subjected to toothbrush-dentifrice abrasion. The amount of vertical
      loss and the surface roughness of each specimen after 20,000 strokes were
      determined with a profilometer. Average values of groups of 5 specimens were
      compared with ANOVA and Duncan new multiple range test. RESULT: Significantly (P
      < .05) less wear was observed with respect to the Targis (10.01 microm; SD = 0.53
      microm) and Estenia (13.04 microm; 1.95 microm) materials than for the other
      composites assessed, whereas Artglass (34.08 microm; 3.66 microm) and Conquest
      Sculpture (31.78 microm; 4.67 microm) materials demonstrated the most wear. The
      least surface roughness was exhibited by Conquest Sculpture (Ra, 0.54 microm;
      0.07 microm) material, and the greatest by Cesead II (1.10 microm; 0.13 microm).
      Ceramic material showed a more wear-resistant (4.54 microm; 0.79 microm) and
      smoother (0.26 microm; 0.02 microm) surface than any of the composite materials.
      CONCLUSION: Abrasion and surface roughness of the prosthetic composites caused by
      toothbrushing varied in accordance with the material. Type of prosthetic
      composite significantly influenced the surface condition after toothbrushing.

PMID- 10898846
TI  - Effect of surface treatments on the wettability of vinyl polysiloxane impression
      materials.
AB  - STATEMENT OF PROBLEM: A number of vinyl polysiloxane (VPS) impression materials
      are claimed to be hydrophilic, but it has been hypothesized that the degree of
      hydrophilicity may be altered by the exposure to saliva, disinfecting agents, and
      surfactants. PURPOSE: This study compared the effects of 6 treatment regimes on
      the hydrophilicity of 3 VPS materials. MATERIAL AND METHODS: Three VPS materials
      (Dimension Garant L, Hydroflex, Imprint II, referred to as G, H, and I,
      respectively) were each treated with: (1) nothing (control), (2) saliva, (3)
      saliva and NaOCl, (4) saliva and 2-propanol-based disinfectant, (5) saliva, NaOCl
      and surfactant, and 6) saliva, 2-propanol-based disinfectant, and surfactant.
      Advancing contact angles (thetaA) were measured using a Cahn Dynamic contact
      angle analyzer and WinDCA software. Using saturated CaSO4 solutions, thetaA was
      determined for the 3 materials in each of the 6 conditions. For each combination
      of VPS and treatment, 5 determinations were made using fresh samples and fresh
      solution each time. Considerable contact angle hysteresis was observed. Two-way
      ANOVA was performed, followed by post-hoc Boneferroni-Dunn tests. RESULTS: For
      all outcome variables, the treatment effects were not the same for all materials
      (P < .001). However, for all materials, treatments that included surfactants were
      among the groups with the lowest thetaA values and thus had the best wettability.
      For example, materials G and I, as made, had high thetaA values (109.7 and 115.2
      degrees, respectively), but these values reduced to approximately 90 degrees
      after surfactant treatment. Material H had a thetaA value of 87.1 degrees.
      Exposure of material H to saliva and/or a disinfectant raised this value, but a
      thetaA close to the original value was achieved by the use of a surfactant.
      CONCLUSION: Treatments affected the VPS materials in different ways but, after
      disinfectant treatment, the wetting of "hydrophilic" VPS materials was improved
      by surfactant treatment.

PMID- 10898847
TI  - Quantitative sensory nerve conduction threshold (sNCT) evaluation of the
      trigeminal nerve at the mental foramen area.
AB  - STATEMENT OF PROBLEM: There is a need for a quick, objective, quantitative
      sensory test of the mandibular inferior alveolar nerve to assess sensory
      dysfunction due to trauma, infection, or disease. PURPOSE: This study evaluated
      the reliability and reproducibility of a commercially available electrodiagnostic
      quantitative sensory nerve conduction threshold (sNCT) evaluation testing method
      and established normative values for future evaluation of nerve dysfunction.
      MATERIAL AND METHODS: Rapid current perception threshold (R-CPT) values were
      obtained with Neurometer CPT/C, an electrodiagnostic sNCT device that administers
      an alternating constant-current sinusoid waveform stimulus at either 2000 Hz (H)
      (Hertz [cycles/second]), 250 Hz (M), or 5 Hz (L) at intensity levels ranging from
      0.001 to 10 mA. Thirty-four healthy subjects were tested then retested by the
      same operator from 7 days to 153 days. R-CPT evaluation was performed over the
      mental foramen bilaterally with dual disposable gold-plated electrodes and a
      hypoallergenic electrode gel held in place using nonconductive adhesive tape. Two
      consecutive identical R-CPT measures were obtained for each stimulation frequency
      for determination of the final R-CPT value. RESULTS: On the left side, there was
      no difference between the first and second test (P > .05). On the right side,
      there was a statistical difference between the first and second test for L, M,
      and H, but the confidence interval is very narrow and the differences are not
      clinically significant. CONCLUSION: From the values obtained, R-CPT testing was
      reliable for the quantification of sensory function in healthy individuals.

PMID- 10898848
TI  - Prefabricated acrylic resin bars for splinting implant transfer copings.
AB  - Splinting of implant transfer copings with acrylic resin during impression
      procedures is performed to accurately transfer the spatial relationships of
      implants to the master cast. However, distortion may occur during the splinting
      procedure because of resin polymerization shrinkage. This article describes a
      simple technique for minimizing this effect by fabrication of resin bars.

PMID- 10898849
TI  - Simple method of boxing a final impression.

PMID- 10898850
TI  - Reinforcement of facial prosthetic dental stone molds.

PMID- 10898851
TI  - Occlusal variables are only moderately useful in the diagnosis of
      temporomandibular disorder.

PMID- 10898852
TI  - Reply

PMID- 10898853
TI  - Abasic DNA structure, reactivity, and recognition.
AB  - Loss of a base in DNA, i.e., creation of an abasic site leaving a deoxyribose
      residue in the strand, is a frequent lesion that may occur spontaneously, or
      under the action of radiations and alkylating agents, or enzymatically as an
      intermediate in the repair of modified or abnormal bases. The abasic site lesion
      is mutagenic or lethal if not repaired. From a chemical point of view,the abasic
      site is an alkali-labile residue that leads to strand breakage through beta- and
      delta- elimination. Progress in the understanding of the chemistry and enzymology
      of abasic DNA largely relies upon the study of synthetic abasic duplexes. Several
      efficient synthetic methods have thus been developed to introduce the lesion (or
      a stable analogue) at defined position in the sequence. Physicochemical and
      spectroscopic examination of such duplexes, including calorimetry, melting
      temperature, high-field nmr and molecular modeling indicate that the lesion
      strongly destabilizes the duplex, although remaining in the canonical B-form with
      structural modifications strictly located at the site of the lesion. Probes have
      been developed to titrate the damage in DNA in vitro. Series of molecules have
      been devised to recognize specifically the abasic site, exhibiting a cleavage
      activity and mimicking the AP nucleases. Others have been prepared that bind
      strongly to the abasic site and show promise in potentiating the cytotoxic and
      antitumor activity of the clinically used nitrosourea (bis
      chloroethylnitrosurea).

PMID- 10898854
TI  - Electrostatic factors in DNA intercalation.
AB  - The factors that determine the binding of a chromophore between the base pairs in
      DNA intercalation complexes are dissected. The electrostatic potential in the
      intercalation plane is calculated using an accurate ab initio based distributed
      multipole electrostatic model for a range of intercalation sites, involving
      different sequences of base pairs and relative twist angles. There will be a
      significant electrostatic contribution to the binding energy for chromophores
      with a predominantly positive electrostatic potential, but this varies
      significantly with sequence, and somewhat with twist angle. The usefulness of
      these potential maps for understanding the binding of intercalators is explored
      by calculating the electrostatic binding energy for 9-aminoacridine, ethidium,
      and daunomycin in a variety of model binding sites. The electrostatic forces play
      a major role in the positioning of an intercalating 9-aminoacridine and a
      significant stabilizing role in the binding of ethidium in its sterically
      constrained position, but the intercalation of daunomycin is determined by the
      side-chain binding. Sequence preferences are likely to be determined by a complex
      and subtle mixture of effects, with electrostatics being just one component. The
      electrostatic binding energy is also unlikely to be a major determinant of the
      twist angle, as its variation with angle is modest for most intercalation sites.
      Overall, the electrostatic potential maps give guidance on how positively charged
      chromophores can be chemically adapted by heteroatomic substitution to optimise
      their binding.

PMID- 10898855
TI  - Controllable stability of DNA-containing polyelectrolyte complexes in water-salt
      solutions.
AB  - Destruction of polyelectrolyte complexes (PECs) formed by DNA and synthetic
      polyamines of different structures was carried out by addition of low molecular
      weight electrolyte to PEC solution at different pHs. The dissociation was studied
      by the fluorescence quenching technique using the ability of cationic dye
      ethidium bromide to intercalate into free sites of DNA double helix followed by
      ignition of ethidium fluorescence. Structure of amine groups of the polycation
      was shown to be a decisive factor of PEC stability. PECs formed by polycations
      with quaternary amine groups, i.e., poly(N-alkyl-4-vinylpyridinium) bromides,
      poly(N, N-dimethyldiallylammonium) chloride, and ionene bromide, were pH
      independent and the least tolerant to destruction by the added salt. Primary
      amine groups of basic polypeptides poly-L-lysine hydrobromide and poly-L-arginine
      hydrochloride as well as synthetic polycation poly(vinyl-2-aminoethyl ether)
      provided the best stability of PECs in water-salt solutions under wide pH range.
      Moderate and pH-dependent stability was revealed for PECs included poly(N,N
      dimethylaminoethylmethacrylate) with tertiary amine groups in the chain or
      branched poly(ethylenimine) with primary, secondary, and tertiary amine groups in
      the molecule. The data obtained appear to be the basis for design of DNA
      containing PECs with given and controllable stability. The design may be
      accomplished not only by proper choice of polyamine of one or another type, but
      by using of tailor-made polycations with given composition of amine groups of
      different structure in the chain as well. Thus, quaternization of a part of
      tertiary amine groups of poly(N, N-dimethylaminoethylmethacrylate) resulted in
      expected decrease of stability of DNA-containing PECs in water-salt solutions.
      The destruction of PEC formed by random copolymer of 4-vinylpyridine and N-ethyl
      4-vinylpyridinium bromide was pH sensitive and could be performed under pH and
      ionic strength closed to the physiological conditions. This result appears to be
      particularly promising for addressing DNA packed in PEC species to the target
      cell.

PMID- 10898856
TI  - The reactive extraction of phenylalanine with Aliquat 336: buffer co-extraction
      equilibrium and mass transfer kinetics.
AB  - The occurrence of significant co-extraction of buffer anions by the ion exchanger
      Aliquat 336 is unavoidable when high levels of system buffering is required. The
      co-extraction will result in inaccurate equilibrium and mass-transfer
      characterization of such a system unless its occurrence is taken into account,
      making process design and control difficult. A study of the equilibrium of
      phenylalanine extraction using Aliquat 336, a system where high levels of
      hydroxyl co-extraction occurs, was used as a model case to develop a method of
      accounting for co-extraction in mass-transfer modeling. Analysis of the
      equilibrium between bulk-aqueous-phase chloride and phenylalanine concentrations
      during mass transfer in a stirred-transfer cell showed there to be linear
      equilibrium relationships between the two parameters for a given extraction
      system of the form C(Cl,t) = alpha(C(A,t) - C(A,0)) for forward extraction and
      C(Cl,t) = epsilon C(A,t) + C(Cl,0) for backward extraction. The constants of
      proportionality of these relationships, or the "co-extraction constants," alpha
      and epsilon, were shown to be related to the selectivity of Aliquat 336 for the
      phenylalanine anion by the relationships alpha = -(1/S + 1) and epsilon; = -(1/S(
      1) + 1). The linear equilibrium relationships were used to develop two-film
      theory mass-transfer models for both forward and backward extraction that account
      for co-extraction. These showed much higher accuracy in modeling stirred-transfer
      cell data than the equivalent models which ignored co-extraction.

PMID- 10898857
TI  - Hydrogen production by Anabaena variabilis PK84 under simulated outdoor
      conditions.
AB  - Hydrogen production by autotrophic, vanadium-grown cells of Anabaena variabilis
      PK84, a cyanobacterial mutant impaired in the utilization of molecular hydrogen,
      has been studied under simulated outdoor conditions. The cyanobacterium was
      cultivated in an automated helical tubular photobioreactor (4.35 L) under air
      containing 2% CO(2), with alternating 12-h light (36 degrees C) and 12-h dark (14
      degrees to 30 degrees C) periods. A. variabilis steadily produced H(2) directly
      in the photobioreactor during continuous cultivation for 2.5 months. The maximum
      H(2) production by the continuously aerated culture under light of 332 microE. s(
      1). m(-2) was 230 mL per 12-h light period per photobioreactor and was observed
      at a growth density corresponding to 3.6 to 4.6 microgram Chl a. mL(-1) (1.2 to
      1.6 mg dry weight. mL(-1)). Replacement of air with an argon atmosphere enhanced
      H(2) evolution by a factor of 2. This stimulatory effect was caused mainly by
      N(2) deprivation in the cell suspension. A short-term decrease of the CO(2)
      concentration in the air suppressed H(2) evolution. Anoxygenic conditions over
      the dark periods had a negative effect on H(2) production. The peculiarity of
      hydrogen production and some physiological characteristics of A. variabilis PK84
      during cultivation in the photobioreactor under a light-dark regime are
      investigated.

PMID- 10898858
TI  - Characterization of Trichoderma reesei cellobiohydrolase Cel7A secreted from
      Pichia pastoris using two different promoters.
AB  - Heterologous expression of T. reesei cellobiohydrolase Cel7A in a methylotrophic
      yeast Pichia pastoris was tested both under the P. pastoris alcohol oxidase
      (AOX1) promoter and the glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter
      in a fermentor. Production of Cel7A with the AOX1 promoter gave a better yield,
      although part of the enzyme expressed was apparently not correctly folded. Cel7A
      expressed in P. pastoris is overglycosylated at its N-glycosylation sites as
      compared to the native T. reesei protein, but less extensive than Cel7A expressed
      in Saccharomyces cerevisiae. The k(cat) and K(m) values for the purified protein
      on soluble substrates are similar to the values found for the native Trichoderma
      Cel7A, whereas the degradation rate on crystalline substrate (BMCC) is somewhat
      reduced. The measured pH optimum also closely resembles that of purified T.
      reesei Cel7A. Furthermore, the hyperglycosylation does not affect the
      thermostability of the enzyme monitored with tryptophane fluorescence and
      activity measurements. On the other hand, CD measurements indicate that the
      formation of disulfide bridges is an important step in the correct folding of
      Cel7A and might explain the difficulties encountered in heterologous expression
      of T. reesei Cel7A. The constitutive GAP promoter expression system of P.
      pastoris is nevertheless well suited for activity screening of cellulase
      activities in microtiter plates. With this type of screening method a faster
      selection of site-directed and random mutants with, for instance, an altered
      optimum pH is possible, in contrast to the homologous T. reesei expression
      system.

PMID- 10898859
TI  - Physiological state-specific models in estimation of recombinant Escherichia coli
      fermentation performance.
AB  - Implementation of advanced control strategies in bioprocesses is often hindered
      by the lack of on-line measurements reflecting the physiological state of the
      culture. Although a number of techniques have been used to estimate key variables
      from data monitored on-line, these often do not explicitly take into account
      changes in physiological state and information on many aspects of physiological
      state that may not be present in on-line data. Here we demonstrate that data
      obtained from chemical fingerprinting methods, such as pyrolysis mass
      spectrometry, can be used to identify changes in the physiological state during
      cultivation. This information can be utilized for the estimation of the
      physiological state and can enable physiological state-specific-model development
      for on-line bioprocess control.

PMID- 10898860
TI  - Effect of diffusive and convective substrate transport on biofilm structure
      formation: a two-dimensional modeling study.
AB  - A two-dimensional model for quantitative evaluation of the effect of convective
      and diffusive substrate transport on biofilm heterogeneity was developed. The
      model includes flow computation around the irregular biofilm surface, substrate
      mass transfer by convection and diffusion, biomass growth, and biomass spreading.
      It was found that in the absence of detachment, biofilm heterogeneity is mainly
      determined by internal mass transfer rate of substrates and by the initial
      percentage of carrier-surface colonization. Model predictions show that biofilm
      structures with highly irregular surface develop in the mass transfer-limited
      regime. As the nutrient availability increases, there is a gradual shift toward
      compact and smooth biofilms. A smaller fraction of colonized carrier surface
      leads to a patchy biofilm. Biofilm surface irregularity and deep vertical
      channels are, in this case, caused by the inability of the colonies to spread
      over the whole substratum surface. The maximum substrate flux to the biofilm was
      greatly influenced by both internal and external mass transfer rates, but not
      affected by the inoculation density. In general, results of the present model
      were similar to those obtained by a simple diffusion-reaction-growth model.

PMID- 10898861
TI  - Optical properties of Nannochloropsis sp and their application to remote
      estimation of cell mass.
AB  - The absorption and scattering coefficients and reflectance spectra of ultra-high
      density Nannochloropsis occulata cultures were investigated in detail to identify
      the optical properties of the cultures and devise algorithms for remote
      estimation of dry cell mass in ultra-high cell density cultures. High-spectral
      resolution measurements of apparent absorption and attenuation as well as
      reflectance from 400 to 900 nm were carried out in relation to the dry weight,
      cell count, and pigment concentration in outdoor cultures. Indices calculated as
      (R(NIR) - R(red))/(R(NIR) + R(red)) and R(NIR)/R(red), in which R(NIR) is
      reflectance in the range from 750 to 800 nm and R(red) is reflectance in the
      range 670-680 nm, were used for remote assessment of dry cell mass. Remote
      estimation in the range 1 to 8 g/L was accomplished with an error of less than
      0.66 g/L. A different index, i.e., (R(NIR) - R(red)) was employed for estimation
      of cell-chlorophyll concentration. This is the first report of in vivo specific
      absorption coefficient of chlorophyll-a and specific scattering coefficient per
      dry algal weight of Nannochloropsis sp., providing a basis for remote monitoring
      of dense phytoplankton masses.

PMID- 10898862
TI  - Effects of Ca(OH)(2) treatments ("overliming") on the composition and toxicity of
      bagasse hemicellulose hydrolysates.
AB  - Hemicellulose syrups from dilute sulfuric acid hydrolysates of hemicellulose
      contain inhibitors that prevent efficient fermentation by yeast or bacteria. It
      is well known that the toxicity of these hydrolysate syrups can be ameliorated by
      optimized "overliming" with Ca(OH)(2). We have investigated the optimization of
      overliming treatments for sugar cane bagasse hydrolysates (primarily pentose
      sugars) using recombinant Escherichia coli LY01 as the biocatalyst. A comparison
      of composition before and after optimal overliming revealed a substantial
      reduction in furfural, hydroxymethylfurfural, and three unidentified high
      performance liquid chromatography (HPLC) peaks. Organic acids (acetic, formic,
      levulinic) were not affected. Similar changes have been reported after overliming
      of spruce hemicellulose hydrolysates (Larsson et al., 1999). Our studies further
      demonstrated that the extent of furan reduction correlated with increasing
      fermentability. However, furan reduction was not the sole cause for reduced
      toxicity. After optimal overliming, bagasse hydrolysate was rapidly and
      efficiently fermented (>90% yield) by LY01. During these studies, titration, and
      conductivity were found to be in excellent agreement as methods to estimate
      sulfuric acid content. Titration was also found to provide an estimate of total
      organic acids in hydrolysate, which agreed well with the sum of acetic,
      levulinic, and formic acids obtained by HPLC. Titration of acids, measurement of
      pH before and after treatment, and furan analyses are proposed as relatively
      simple methods to monitor the reproducibility of hydrolysate preparations and the
      effectiveness of overliming treatments.

PMID- 10898863
TI  - Effect of carbon and nitrogen sources on growth dynamics and exopolysaccharide
      production for the hyperthermophilic archaeon Thermococcus litoralis and
      bacterium Thermotoga maritima.
AB  - Batch and continuous cultures were used to compare specific physiological
      features of the hyperthermophilic archaeon, Thermococcus litoralis (T(opt) of 85
      degrees to 88 degrees C), to another fermentative hyperthermophile that reduces S
      degrees facultatively, that is, the bacterium Thermotoga maritima (T(opt) of 80
      degrees to 85 degrees C). Under nutritionally optimal conditions, these two
      hyperthermophiles had similar growth yields on maltose and similar cell formula
      weights based on elemental analysis: CH(1.7)O(0. 7)N(0.2)S(0.006) for T.
      litoralis and CH(1.6)O(0.6)N(0.2)S(0.005) for T. maritima. However, they differed
      with respect to nitrogen source, fermentation product patterns, and propensity to
      form exopolysaccharides (EPS). T. litoralis could be cultured in the absence or
      presence of maltose on an amino acid-containing defined medium in which amino
      acids served as the sole nitrogen source. T. maritima, on the other hand, did not
      utilize amino acids as carbon, energy, or nitrogen sources, and could be grown in
      a similar defined medium only when supplemented with maltose and ammonium
      chloride. Not only was T. litoralis unable to utilize NH(4)Cl as a nitrogen
      source, its growth was inhibited at certain levels. At 1 g/L ( approximately 20
      mM) NH(4)Cl, the maximum growth yield (Y(x/s(max))) for T. litoralis was reduced
      to 13 g cells dry weight (CDW)/mol glucose from 40 g CDW/mol glucose in media
      lacking NH(4)Cl. Alanine production increased with increasing NH(4)Cl
      concentrations and was most pronounced if growth on NH(4)Cl was carried out in an
      80% H(2) atmosphere. In T. maritima cultures, which would not grow in an 80% H(2)
      atmosphere, alanine and EPS were produced at much lower levels, which did not
      change with NH(4)Cl concentration. EPS production rose sharply at high dilution
      rates for both organisms, such that maltose utilization plots were biphasic. Wall
      growth effects were also noted, because cultures failed to wash out at dilution
      rates significantly above maximum growth rates determined from batch growth
      experiments. This study illustrates the importance of effective cultivation
      methods for addressing physiological issues related to the growth of
      hyperthermophilic heterotrophs.

PMID- 10898864
TI  - Growth of Ca-D-malate crystals in a bioreactor.
AB  - To develop a bioreactor for solid-to-solid conversions, the conversion of solid
      Ca-maleate to solid Ca-D-malate by permeabilized Pseudomonas pseudoalcaligenes
      was studied. In a bioreactor seeded with product (Ca-D-malate) crystals, growth
      of Ca-D-malate crystals is the last step in the solid-to-solid conversion and is
      described here. Crystal growth is described as a transport process followed by
      surface processes. In contrast to the linear rate law obeyed by the transport
      process, the surface processes of a crystal-growth process can also obey a
      parabolic or exponential rate law. Growth of Ca-D-malate crystals from a
      supersaturated aqueous solution was found to be surface-controlled and obeyed an
      exponential rate law. Based on this rate law, a kinetic model was developed which
      describes the decrease in supersaturation due to Ca-D-malate crystal growth as a
      function of the constituent ions, Ca(2+) and D-malate(2-). The kinetic parameters
      depended on temperature, but, as expected (surface-controlled), they were hardly
      affected by the stirring speed.

PMID- 10898865
TI  - A novel high-pressure liquid-liquid extraction process for downstream processing
      in biotechnology: extraction of cardiac glycosides.
AB  - This investigation examines phase equilibrium phenomena that can be used to
      create two water-like solvents for liquid-liquid extraction in downstream
      processing in biotechnology: a completely miscible, binary liquid mixture of
      water and a hydrophilic organic solvent (e. g., an alcohol) reveals a liquid
      phase split, when it is pressurized with a "near-critical" gas (i.e., a substance
      which at ambient conditions is a gas, near its critical temperature). This phase
      split results in two hydrophilic liquid phases. Making use of this phenomenon in
      process development first requires research on the phase split phenomenon and,
      second, research on the feasibility of biomolecule extraction and separation. In
      this study, basic fluid phase equilibrium phenomena are briefly described. Then,
      experimental results are reported for the partitioning of small amounts of
      cardiac glycosides (digitoxin and digoxin) on coexisting liquid phases in the
      high-pressure, three-phase, vapor-liquid-liquid equilibrium of the ternary system
      of "near critical" CO(2) + water + 1-propanol, at 313 K and 333 K. Finally, a
      process for extraction and separation of the aforementioned glycosides by means
      of the high-pressure phase equilibrium phenomenon is discussed.

PMID- 10898866
TI  - Phosphate feeding improves high-cell-concentration NS0 myeloma culture
      performance for monoclonal antibody production.
AB  - Phosphorus depletion was identified in high-cell-concentration fed-batch NS0
      myeloma cell cultures producing a humanized monoclonal antibody (MAb). In these
      cultures, the maximum viable and total cell concentration was generally ca. 5 x
      10(9) and 7 x 10(9) cells/L, respectively, without phosphate feeding. Depletion
      of essential amino acids, such as lysine, was initially thought to cause the
      onset of cell death. However, further improvement of cell growth was not achieved
      by feeding a stoichiometrically balanced amino acid solution, which eliminated
      depletion of amino acids. Even though a higher cell viability was maintained for
      a longer period, no increase in total cell concentration was observed.
      Afterwards, phosphorus was found to be depleted in these cultures. By also
      feeding a phosphate solution to eliminate phosphorus depletion, the cell growth
      phase was prolonged significantly, resulting in a total cell concentration of ca.
      17 x 10(9) cells/L, which is much greater than ca. 7 x 10(9) cells/L without
      phosphate feeding. The maximum viable cell concentration reached about 10 x 10(9)
      cells/L, twice as high as that without phosphate feeding. Apoptosis was also
      delayed and suppressed with phosphate feeding. A nonapoptotic viable cell
      population of 6.5 x 10(9) cells/L, as compared with 3 x 10(9) cells/L without
      phosphate feeding, was obtained and successfully maintained for about 70 h. These
      results are consistent with the knowledge that phosphorus is an essential part of
      many cell components, including phospholipids, DNA, and RNA. As a result of
      phosphate feeding, a much higher integral of viable cell concentration over time
      was achieved, resulting in a correspondingly higher MAb titer of ca. 1.3 g/L. It
      was also noted that phosphate feeding delayed the cell metabolism shift from
      lactate production to lactate consumption typically observed in recombinant NS0
      cultures. The results highlight the importance of phosphate feeding in high-cell
      concentration NS0 cultures.

PMID- 10898867
TI  - Improving lipase enantioselectivity in organic solvents by forming substrate
      salts with chiral agents.
AB  - We recently demonstrated (J Am Chem Soc 121:3334-3340, 1999) that enzymatic
      enantioselectivity in organic solvents can be markedly enhanced by temporarily
      enlarging the substrate via salt formation. In the present study, this approach
      was expanded by finding that, in addition to its size, the stereochemistry of the
      counterion can greatly affect the enantioselectivity enhancement. For example,
      the enantioselectivity [E = (k(cat)/K(M))(S)/(k(cat)/K(M))(R)] of crystalline
      Pseudomonas cepacia lipase in the propanolysis of phenylalanine methyl ester
      (PheOMe) in anhydrous acetonitrile was found to be 5.8 +/- 0.6; the E value
      doubled when PheOMe's salt with S mandelic acid was used as a substrate instead
      of the free ester, and rose sevenfold with R mandelic acid as a Bronsted-Lowry
      acid. Similar effects were observed with other bulky, but not petite,
      counterions. The greatest enantioselectivity enhancement was afforded by 10
      camphorsulfonic acid: the E value increased to 18 +/- 2 for a salt with its R
      enantiomer and jumped to 53 +/- 4 for the S. These effects, also observed in
      other organic solvents, were explained by means of structure-based molecular
      modeling of the lipase-bound transition states of the substrate enantiomers and
      their diastereomeric salts.

PMID- 10898868
TI  - Dental biomaterials

PMID- 10898869
TI  - Effect of magnesium content on the microstructure and crystalline phases of
      fluoramphibole glass-ceramics.
AB  - The purpose of this study was to evaluate the effect of magnesium content on the
      microstructure and crystalline phases of glass-ceramics in the system SiO(2)-MgO
      CaO-Na(2)O-K(2)O-F. Four glass compositions were prepared with magnesium content
      varying from 12-18 wt%. The compositions were melted at 1400 degrees C for 2 h
      and cast into 30 x 8 mm ingots. Differential thermal analyses were performed on
      the powdered glasses at a heating rate of 20 degrees C/minute up to 1400 degrees
      C. Bars (4 x 8 x 25 mm) were cut from the ingots with a low-speed diamond saw,
      nucleated in the temperature range 600-650 degrees C for 1-2 h and crystallized
      in the temperature range 900-1000 degrees C for 4-6 h. The crystalline phases
      were analyzed by X-ray diffraction. The microstructure was investigated by
      scanning electron microscopy. The Vickers hardness was determined after
      indentation under a 9.81 N load. Differential thermal analyses revealed that
      crystallization occurred in the temperature range 700-800 degrees C. X-ray
      diffraction showed the presence of fluorrichterite as major crystalline phase
      regardless of the magnesium content in the parent glass or heat treatment
      temperature. The microstructure consisted of interlocked acicular crystals (5-10
      micrometers). The highest magnesium content led to the coexistence of both a mica
      phase and fluorrichterite. This microstructure promoted crack deflections and
      arrest.

PMID- 10898870
TI  - A comparison of the microstructure and properties of the IPS Empress 2 and the
      IPS Empress glass-ceramics.
AB  - The aim of this report is to analyze the microstructures of glass-ceramics of the
      IPS Empress 2 and IPS Empress systems by scanning electron microscopy. The main
      properties of the glass-ceramics were determined and compared to each other. The
      flexural strength of the pressed glass-ceramic (core material) was improved by a
      factor of more than three for IPS Empress 2 (lithium disilicate glass-ceramic) in
      comparison with IPS Empress (leucite glass-ceramic). For the fracture toughness,
      the K(IC) value was measured as 3.3 +/- 0.3 MPa. m(0.5) for IPS Empress 2 and 1.3
      +/- 0.1 MPa. m(0.5) for IPS Empress. Abrasion behavior, chemical durability, and
      optical properties such as translucency of all glass-ceramics fulfill the dental
      standards. The authors concluded that IPS Empress 2 can be used to fabricate 3
      unit bridges up to the second premolar.

PMID- 10898871
TI  - Strength and reliability of surface treated Y-TZP dental ceramics.
AB  - This work was undertaken to evaluate the effects of dental grinding and
      sandblasting on the biaxial flexural strength and Weibull modulus of various Y
      TZP ceramics containing 3 mol% yttria. In addition, the susceptibility of
      pristine and mechanically treated materials to low-temperature degradation under
      the conditions adopted for testing the chemical solubility of dental ceramics was
      investigated. The results revealed that surface grinding and sandblasting exhibit
      a counteracting effect on the strength of Y-TZP ceramics. Dental grinding lowered
      the mean strength and Weibull modulus, whereas sandblasting provided a powerful
      method for strengthening, but at the expense of somewhat lower reliability. The
      finest-grained material exhibited the highest strength after sintering, but it
      was less damage tolerant than tougher, coarse-grained materials. Upon extraction
      with the acetic acid solution and the ammonia solution, a significant amount of
      tetragonal zirconia had transformed to monoclinic, but extensive microcracking
      and attendant strength degradation had not yet occurred. Standard grade Y-TZP
      ceramics are more resistant in an alkaline than in an acidic environment, and
      there was a strong grain-size dependence of the diffusion-controlled
      transformation. Since a special Y-TZP grade containing a small amount of alumina
      exhibited the highest damage tolerance and superior stability in an acidic
      environment, this material shows considerable promise for dental applications.

PMID- 10898872
TI  - A comparison of mechanical properties of all-ceramic alumina dental crowns
      prepared from aqueous- and non-aqueous-based tape casting.
AB  - Alumina-glass dental composites were prepared by aqueous- and non-aqueous-based
      tape casting and sintering at 1120 degrees C, followed by glass infiltration at
      1100 degrees C. Flexural strength and fracture toughness of the composites were
      investigated in terms of influence of tape constituents, namely, alumina powder,
      binder, and plasticizer on the mechanical properties. For the alumina-glass
      composites prepared from the aqueous-based tapes, both strength and toughness
      increased with increasing alumina fraction ratio in tape constituents including
      organic substances, a/a+o, and binder content ratio in binder/binder +
      plasticizer mixture, b/b+p. For the composites prepared from the non-aqueous
      based tapes, on the other hand, both strength and toughness increased with
      increasing the a/a+o ratio but decreased with increasing the b/b+p ratio. These
      observations were consistent with influence of the constituents on mean alumina
      particle distance in tapes, suggesting that high strength of the glass
      infiltrated alumina composites is related to toughening by crack bowing. The
      optimized strength of the aqueous and nonaqueous tape cast composites was 559 and
      508 MPa, and the fracture toughness was 3.3 and 3.1 MPam(1/2), respectively.

PMID- 10898873
TI  - Advanced biomaterials used for a new telescopic retainer for removable dentures.
AB  - Removable dentures supported by cast-metal telescopic crowns often exhibit an
      unpredictable increase or decrease in retentive force after being in clinical use
      for some time. The objective of the present in vitro study was to develop a new
      retainer for removable dentures and to evaluate its tribological properties. The
      new retainer is based on a tapered crown design and consists of a conical all
      ceramic abutment crown and a coping made of electroplated gold. It was compared
      with conventional telescopic retainers made of cast metal. There were 30
      specimens in groups of equal size by material used (abutment crown/coping): Group
      1, gold/gold; Group 2, titanium/titanium; Group 3, ceramic/electroplated gold.
      Each specimen consisted of 2 conical-shaped abutment crowns (alpha =4 degrees; h
      = 6 mm; O(base) = 4,5 mm); their copings were rigidly connected at 25 mm
      intervals. Retentive forces were measured with a universal testing machine
      following axial loading to 5-400 N. Wear was simulated by 500-100, 000 joining
      and separating cycles in the presence of artificial saliva. Metallographic cross
      sections were made to evaluate the specimens' fit and surfaces with an SEM.
      Retentive forces in Groups 1 and 2 increased with load, exhibiting nondirectional
      changes after induced wear. Sometimes the alloys' functional surfaces showed
      considerable tracks of wear. Neither load nor wear had any effect on Group 3
      retentive forces (mean(force) = 5.03 N). The functional ceramic and gold surfaces
      showed no traces of wear and the best fit (median(gap) = 4.9 microm). Replacing
      cast metals by ceramics and electroplated gold results in retainers with
      clinically advantageous tribological effects, implying, in particular, high wear
      resistance.

PMID- 10898874
TI  - Advanced biomaterials used for a new telescopic retainer for removable dentures.
AB  - Telescopic retainers with conical ceramic abutment crowns and electroplated gold
      copings define a new retainer for removable dentures exhibiting favorable
      tribological properties that could offer clinical advantages. The objective of
      this study was to evaluate the clinical effects of this retainer. To do so, a
      novel treatment modality was developed based on intraoral bonding of the copings
      to the framework in order to be able to realize, in a clinical setting, the
      retainer function based on a precision fit. A total of 32 patients wearing 33
      dentures (16 mandibular, 17 maxillary; period of risk [months]: minimum = 3;
      maximum = 58; mean = 27.6), supported by 147 abutments (83 natural teeth, 64
      implants) with ceramic abutment crowns (IPS Empress 1, IPS Empress 2, InCeram,
      Procera, CerAdapt; CeraBase) were followed at 6-month intervals. The ceramic
      abutment crowns showed low plaque accumulation (mean PI = 17.3%). The gingival
      tissues around natural abutments were generally free of inflammation; so was the
      mucosa around the implants (mean SBI = 4.9%). Denture adhesion and occlusion did
      not change, and there were no rocking movements. The mobility (as determined by
      Periotest) of 29 teeth was reduced in a highly significant manner within 6 months
      (t test, p < 0.001). Osseointegration was preserved for all implants. One
      abutment loosened. Six Empress 1 ceramic copings failed (94.6% Kaplan-Meier
      survival rate), and one abutment tooth was lost (99.2% survival rate). All
      patients reported problem-free handling, no rocking movements, and constant
      adhesion. The adhesive strength of one denture was too low at insertion. 94% of
      the patients experienced no problems with oral hygiene. The retainer examined has
      relevant clinical advantages and meets geriatric requirements for removable
      dentures.

PMID- 10898875
TI  - Machinability of IPS Empress 2 framework ceramic.
AB  - Using ceramic materials for an automatic production of ceramic dentures by
      CAD/CAM is a challenge, because many technological, medical, and optical demands
      must be considered. The IPS Empress 2 framework ceramic meets most of them. This
      study shows the possibilities for machining this ceramic with economical
      parameters. The long life-time requirement for ceramic dentures requires a
      ductile machined surface to avoid the well-known subsurface damages of brittle
      materials caused by machining. Slow and rapid damage propagation begins at break
      outs and cracks, and limits life-time significantly. Therefore, ductile machined
      surfaces are an important demand for machine dental ceramics. The machining tests
      were performed with various parameters such as tool grain size and feed speed.
      Denture ceramics were machined by jig grinding on a 5-axis CNC milling machine
      (Maho HGF 500) with a high-speed spindle up to 120,000 rpm. The results of the
      wear test indicate low tool wear. With one tool, you can machine eight occlusal
      surfaces including roughing and finishing. One occlusal surface takes about 60
      min machining time. Recommended parameters for roughing are middle diamond grain
      size (D107), cutting speed v(c) = 4.7 m/s, feed speed v(ft) = 1000 mm/min, depth
      of cut a(e) = 0.06 mm, width of contact a(p) = 0.8 mm, and for finishing ultra
      fine diamond grain size (D46), cutting speed v(c) = 4.7 m/s, feed speed v(ft) =
      100 mm/min, depth of cut a(e) = 0.02 mm, width of contact a(p) = 0.8 mm. The
      results of the machining tests give a reference for using IPS Empress(R) 2
      framework ceramic in CAD/CAM systems.

PMID- 10898876
TI  - Mechanical properties of new composite restorative materials.
AB  - OBJECTIVE: Determination of flexural strength, flexural modulus, fracture
      toughness, Vickers hardness, and wear resistance of condensable composites
      (Solitaire, Surefil, Alert) and an ormocer (Definite) in comparison with a hybrid
      composite (Tetric Ceram) and an ion-releasing composite (Ariston pHc). METHODS:
      Flexural strength, flexural modulus, and fracture toughness were determined in 3
      point bending. Single-edge notched-bend specimens were used to evaluate fracture
      toughness. Microhardness was measured with a Vickers indenter. Wear was
      determined in a pin-on-block-design with a Degusit antagonist at 50 N load and
      quantified by a replica technique after 6000, 10000, 30000, and 50000 load cycles
      using a 3D-laser scanner. All results were statistically analyzed with ANOVA and
      post hoc Tukey HSD tests. RESULTS: Alert exhibited the highest flexural modulus,
      K(IC), and hardness, but lowest wear resistance. Solitaire presented the highest
      wear resistance, but significantly lower flexural strength, flexural modulus,
      K(IC), and hardness than all other materials. No significant correlation could be
      detected between hardness and wear of the tested composites with Pearson's
      correlation coefficient. SIGNIFICANCE: The condensable composites differed
      significantly in their mechanical properties. This study suggested that, besides
      the filler content level and filler size, other factors like matrix-filler
      interactions highly influence the fracture and wear behavior of the materials.

PMID- 10898878
TI  - Internal corrosion in dental composite wear.
AB  - The internal corrosion of dental resin composites is associated with water
      sorption and leads to (1) interfacial debonding, (2) filler dissolution, (3)
      matrix cracking, and (4) subsurface damage. The last factor creates a condition
      for "corrosive-wear" in which the damaged layer is worn with ease exposing a new
      surface and perpetuating the cycle of corrosion and wear. Central to the
      simulation of in vivo corrosive-wear is the recreation of the subsurface damage
      layer. To produce this layer in water, artificial saliva, and in media of low pH
      is time-consuming, because the degradation process in these environments is
      extremely slow. In laboratory wear tests using aqueous environments, the contact
      time of resin composites with water is too short to cause significant internal
      degradation. Thus, data obtained from such tests represent abrasive and not
      corrosive-wear, and do not correlate well with in vivo wear data. In considering
      this limitation of the above media for accelerated wear tests, an alkaline medium
      has been used in this study to simulate corrosive-wear of eleven commercial
      composites. The procedure consists of exposing each material to 0.1 N NaOH at 60
      degrees C for 2 weeks followed by abrasion in a tooth brushing machine. The
      medium choice is based on the rationale that in vivo degradation arises from
      reaction with the OH(-), and this reaction can be enhanced by raising the pH and
      the temperature of the medium. The warm NaOH solution satisfies both these
      conditions. Parameters examined to evaluate the resistance of each composite to
      corrosion and wear were (1) mass loss, (2) Si-loss, (3) degradation depth, and
      (4) wear depth, respectively. A highly significant correlation has been observed
      among various corrosion and wear parameters. SEM examination indicated
      degradation to be associated with interfacial separation, filler dissolution,
      matrix cracking, and subsurface damage. These features are characteristics of in
      vivo worn composite restorations. Time is of utmost importance in laboratory
      evaluation of restorative materials. The ability of NaOH to meet this expediency
      and to mimic the in vivo degradation process makes it a useful medium for
      corrosive-wear studies of dental composites.

PMID- 10898877
TI  - Fracture toughness of aged dental composites in combined mode I and mode II
      loading.
AB  - Resin-based laboratory dental composites for prosthetic restorations have been
      developed in the past years as a cost-effective alternative to conventional
      porcelain-fused-to-metal or full ceramic restorations. The fracture toughness at
      different stress states (K(Ic), K(IIc), and mixed-modes K(I), K(II) ) was
      assessed for three laboratory dental composite resins used for prosthetic
      restorations that were aged up to 12 months in a food simulating fluid (10%
      ethanol) at 37 degrees C. The materials were mainly di- methacrylate based resins
      reinforced with submicron glass filler particles. The Brazilian disk test was
      used on precracked chevron-notched specimens, and different stress states were
      obtained by angulating the precracked chevron notch relative to the diametral
      compressive loading direction. The stress intensity factors were calculated using
      Atkinson et al.'s relation. For all three materials, mode I fracture toughness
      values ranged between 0.48-0.64 MPa. m(0.5) and mode II values ranged between
      0.93-1.2 MPa. m(0.5). Overall, aging time and storage media had little effect on
      toughness. Considering the inherently low toughness of these restorative
      materials, their use should be limited to low stress masticatory areas.

PMID- 10898879
TI  - Physicochemical evaluation of bioactive polymeric composites based on hybrid
      amorphous calcium phosphates.
AB  - Amorphous calcium phosphate (ACP)-filled methacrylate composites were recently
      found to effectively remineralize in vitro caries-like enamel lesions. Their
      inferior mechanical properties compared to glass-filled composites, however,
      limit their use as a dental restorative material. In this study, the feasibility
      of introducing glass-forming elements (tetraethoxysilane or zirconyl chloride)
      during the low-temperature synthesis of ACP was investigated. Composites based on
      such hybrid fillers (mass fraction, 40%) were evaluated to establish whether
      hybridization strengthened the composites via improved interfacial interactions
      with the polymer phase without compromising the release of the mineral ions. Two
      types of visible-light cured resins were prepared: BTHZ resin from 2, 2-bis[p-(2'
      hydroxy-3'-methacryloxypropoxy)phenyl]propane (BisGMA), triethylene glycol
      dimethacrylate (TEGDMA), 2-hydroxyethyl methacrylate (HEMA) and zirconyl
      methacrylate (ZrM), and TP resin from TEGDMA and pyromellitic glycerol
      dimethacrylate (PMGDM). Hybridized fillers and BTHZ- and TP-based composites were
      characterized by the IR spectroscopy, X-ray diffraction,
      dissolution/transformation kinetic studies, and biaxial flexure strength (BFS)
      testing before and after immersion in buffered saline solutions. The feasibility
      of improving the BFS via hybridization, while retaining, if not enhancing the
      remineralizing potential was demonstrated for BTHZ-based composites. Both BFS and
      remineralizing ability of the TP-composites, however, deteriorated upon their
      exposure to an aqueous environment. Therefore, hybridized ACP-filled BTHZ
      composites have a potential for utilization in more demanding restorative,
      sealant, and adhesive applications.

PMID- 10898880
TI  - Clinical and histological findings in guided bone regeneration (GBR) around
      titanium dental implants with autogeneous bone chips using a new resorbable
      membrane.
AB  - The aim of this study was to test the value of a polydioxanon-membrane (PDS(R),
      Ethicon, Norderstedt, Germany) in combination with autogenous bone as a spacer
      for guided bone regeneration of denuded implant surfaces in comparison to simple
      augmentation. Altogether, in 8 Beagle dogs of 12 months, the three mandibular
      premolars were extracted on both sides and, after an uneventful healing of the
      extraction sockets in each mandibular site, two seize defined bone defects were
      produced. The defects were 7 mm long, had a vertical extension of 7 mm, and were
      7 mm deep. These also included, therefore, the resection of the lingual cortical
      bone wall. In the center of all these 32 bone defects, Branemark fixtures with a
      diameter of 3 mm and a length of 10 mm were implanted. Every implant was
      primarily stable due to the fixation in the native bone under the created
      defects. In each mandible site, one bone defect was filled with autologous bone
      resulting from the previous defect preparation. Half of the defects were covered
      with a PDS membrane, and the other half were covered only by the relocation of
      the mucoperiosteal flap. During the observation period of 90-180 days, continuous
      clinical and radiological controls were executed. Aside from the observed
      clinical healing problems in the test sites, such as exposure of the membranes
      and serious inflammatory reactions, the histological and radiological results of
      the control group regarding bone regeneration were superior to these of the test
      group, which were valid also for the subgroups with or without autologous bone
      fillings.

PMID- 10898881
TI  - Development, characterization, and anti-microbial efficacy of hydroxyapatite
      chlorhexidine coatings produced by surface-induced mineralization.
AB  - The surface-induced mineralization (SIM) technique was used to produce
      hydroxyapatite (HAP) coatings on external fixation pins with the antimicrobial
      agent, chlorhexidine, incorporated within the coating. The SIM process involved
      surface modification of the substrate with organic functional groups followed by
      immersion in aqueous supersaturated calcium phosphate solutions. X-ray
      diffraction spectra confirmed that hydroxyapatite coatings were formed.
      Chlorhexidine was incorporated into the coating by placing the substrate into
      various chlorhexidine solutions in between mineralization cycles. Total uptake
      was measured by dissolution of the coating into a 0.1 M nitric acid solution and
      measuring the chlorhexidine concentration using UV spectroscopy at 251 nm.
      Release rates were measured by submersion of coated substrates into saline
      solutions and measuring chlorhexidine UV absorbency at 231 nm as a function of
      time. Results show an initial rapid release followed by a period of slower
      sustained release. The anti-microbial efficacy of the HAP-chlorhexidine coatings
      was evaluated in vitro using a Staphylococcus aureus cell culture. Initial
      results show a large "inhibition zone" formed around the chlorhexidine/HAP
      coating vs. coatings with HAP only. This preliminary work clearly demonstrates
      that SIM HAP coatings have great potential to locally deliver antimicrobial
      agents such as chlorhexidine at implantation sites, which may greatly reduce the
      incidence of pin tract infection that occurs in external fixation.

PMID- 10898882
TI  - Glass-matrix biocomposites.
AB  - CaO-SiO(2) base glass-matrix/Ti particle biocomposite coatings on Ti6Al4V
      substrates have been prepared by means of Vacuum Plasma Spray. The base glass is
      considered bioactive, because, when soaked in a fluid that simulates the
      inorganic ion concentration of human plasma (SBF), it develops a bonelike apatite
      layer on its surface. The aim of this research activity was to toughen this
      brittle bioactive material and to broaden its biomedical applications. Pure
      titanium was chosen as toughening phase because of its well-known
      biocompatibility, and Ti6Al4V alloy as substrate because of both its
      biocompatibility and its mechanical reliability. At first the composites were
      prepared as bulk materials, by means of a simple sintering process. Then, by ball
      milling the sintered composite, the as-obtained "composite powders" were sprayed
      by Vacuum Plasma Spray (VPS) on the substrate. By means of Differential Thermal
      Analysis (DTA) and Differential Scanning Calorimetry (DSC), the characteristic
      temperatures of the base glasses were determined. The thermal properties of
      mixtures of glass powders and different vol% Ti particles were studied by means
      of DTA, DSC, hot-stage microscopy, and dilatometry, with the aim of optimizing
      the sintering conditions. Both the bulk and the coated samples have been
      characterized by means of X-ray diffraction (XRD), scanning electron microscopy
      (SEM), compositional analysis (EDS), Vickers indentations, and leaching tests
      after soaking in a simulated body fluid (SBF).

PMID- 10898883
TI  - Selective laser sintering of ultra high molecular weight polyethylene for
      clinical applications.
AB  - Rapid prototyping is a relatively new technology, which although prominent in the
      engineering industry is only just starting to make an impact in the medical
      field. Its current medical uses are mainly confined to surgical planning and
      teaching, but the technology also has the potential to allow for patient-tailored
      prostheses. The work reported here describes the application of a simplified
      selective laser sintering apparatus with ultra high molecular weight polyethylene
      (UHMWPE). The morphology and chemistry of the starting powders and lased material
      have been characterized using Fourier Transform Infra Red spectroscopy and a
      combination of light and scanning electron microscopy. It was found that solid
      linear continuous bodies could be formed, but material shrinkage caused problems
      when trying to form sheet-like structures. The porosity of the formed material
      was also a concern. The material exposed to the laser beam was shown to have
      undergone degradation in terms of chain scission, cross-linking, and oxidation.
      It has been concluded that to apply this technology to the fabrication of UHMWPE
      devices requires the development of improved starting powders, in particular with
      increased density.

PMID- 10898884
TI  - An evaluation of mechanical property and microstructural development in HAP-Ca
      polycarboxylate biocomposites prepared by hot pressing.
AB  - A hot-pressing technique was used to prepare composites anticipated to be
      biocompatible. Ca(4)(PO(4))(2)O (TetCP) was reacted with an acrylic-itaconic
      copolymer (CoP) in the absence of a solvent to form composites comprised of
      Ca(10)(PO(4))(6)(OH)(2') (hydroxyapatite, or HAp) and the Ca polyalkenoate salt.
      The effect of temperature, pressure, and hot-pressing time on the mechanical
      properties and microstructure of the composites were studied. Results showed that
      both tensile strength and elastic modulus increased when temperature and time
      were increased. When the compaction pressure was increased, these properties
      initially increased but decreased at high pressures. These variations in the
      mechanical properties were correlated with the microstructure of these
      composites. The mechanism of the reaction was also studied. Reaction starts when
      the copolymer is heated to above its T(g) permitting it to flow and react with
      the TetCP grains. The COOH groups on the polymer are neutralized by Ca(2+) ions
      liberated from the TetCP. At the end of reaction, a network of the Ca
      polyalkenoate salt is formed in which HAp crystals are embedded.

PMID- 10898885
TI  - Reconstruction of alveolar bone defect by calcium phosphate compounds.
AB  - Osteoconductivity of newly developed calcium phosphate cements (CP-1, CP-2) was
      estimated in mandibular periapical alveolar bone of rats. The powder phase of CP
      1 was an equimolar mixture of tetracalcium phosphate and dicalcium phosphate
      dihydrate, and that of CP-2 was alpha-tricalcium phosphate. The liquid phase of
      CP-1 and CP-2 was a solution containing tannic acid and citric acid. CP-1, CP-2,
      an apatitic sealer (ARS), or a zinc oxide eugenol sealer (ZOE) was respectively
      applied in the mechanically injured periapical regions through the root canals of
      both mandibular first molars of 15 rats. A further 15 rats were used as controls
      with no material in the region. The results of histopathological examination at
      1, 3, and 5 weeks after operation were analyzed by the chi(2) test (95%
      confidence level). At 1 week, foreign-body giant cells were observed around CP-1
      and CP-2, but not around ARS or ZOE. Congestion of small blood vessels was seen
      in bone defect areas of the controls. After 5 weeks, statistically significant
      bone reconstruction was induced by application of CP-1 (80.0%), CP-2 (90.0%)
      compared with ARS (33.3%). Fibrous scaring was seen in the controls. It is
      concluded that resolvability of CP-1 and CP-2 should contribute to osseous
      healing.

PMID- 10898886
TI  - Mechanical properties, phase stability, and biocompatibility of (Y, Nb)
      TZP/Al(2)O(3) composite abutments for dental implant.
AB  - ZrO(2)/Al(2)O(3) composites were prepared by mixing a tetragonal ZrO(2),
      stabilized by 5.31 mol% Y(2)O(3) and 4.45 mol% Nb(2)O(5), and various amounts of
      Al(2)O(3). Influence of the amount of Al(2)O(3) on strength and toughness and
      tetragonal phase stability in the composites under autoclave conditions was
      investigated. In addition, in vitro and in vivo biocompatibility of the
      composites was examined. The composite, prepared with addition of 20 vol%
      Al(2)O(3), exhibited the highest strength of 700 MPa and toughness of 8.1 MPa.
      m(1/2) and showed no hydrothermal degradation while aging in an autoclave. The
      biocompatibility of the composite exhibited no cytotoxicity and no significant
      adverse soft-tissue response for up to 3 months implant period in guinea pigs.

PMID- 10898887
TI  - Neurologist or psychiatrist? The public and private domains of Jean-Martin
      Charcot.
AB  - The emergence of neurology as an autonomous, prestigious field in late-nineteenth
      century Paris is well known. Less appreciated is the role that neurologists
      played vis-a-vis the cognate older field of psychiatry. Taking Jean-Martin
      Charcot, the most influential neurologist of his time, as a test case, this paper
      contrasts his attitudes and practice in the public setting of teaching and
      hospital work with his private practice. A staunch defender of a clear
      distinction between his field and psychiatry, Charcot's private practice
      displayed more flexibility. Treating hysteria and neurasthenia created a middle
      ground of nervous diseases for him to cultivate. Unpublished case histories and
      other materials, especially from the Charcot library, support the conception of
      neurologists as active agents in constituting a new psychological medicine.

PMID- 10898888
TI  - How Pierre Janet used pathological psychology to save the philosophical self.
AB  - According to traditional French historiography, French scientific psychology was
      born when it differentiated itself from philosophy. This split between the two
      disciplines is attributed to Taine and Ribot, who, consequently, are considered
      to be the "founding fathers" of French psychology. In this paper we shall examine
      the case of Pierre Janet, who, at the turn of the century, was recognized
      worldwide as the most important French psychologist. It is generally said that he
      was the follower of Ribot and of Charcot. However, he was also Paul Janet's
      nephew. Paul Janet was a very well known and influential philosopher of the so
      called French "spiritualistic" school, for which psychology was central to
      philosophy. In 1889, Pierre Janet published his doctoral dissertation,
      L'Automatisme psychologique, which was immediately considered to be a classic in
      psychology. We shall argue that this book is as much indebted to the old
      spiritualistic psychology, which claimed the substantial unity of the self, as to
      the new psychology at the time, which questioned it. With Pierre Janet, the split
      between psychology and philosophy in France was reconsidered. It would be more
      accurate to speak in terms of a compromise between philosophy and the "new"
      physiological and pathological psychology.

PMID- 10898890
TI  - Briefly noted

PMID- 10898891
TI  - News and notes

PMID- 10898889
TI  - Max Weber's methodology: an ideal-type.
AB  - Weber dealt-in contrast to the textbook image of his method-with rational and
      nonempathetic explanatory interpretation. His ideal-type for social action
      emerged in a very formative period, as a mediation between history and theory and
      can be characterized as releasing what was inherent in a historicist tradition in
      crisis. Theoretical elements from Austrian marginalism provided Weber with the
      prototype for developing contrafactual schemes into ideal-types. Weber as a
      scholar at the crossroads resolved the problem of uncontrolled value-intrusion in
      a way that provided rational evidence and limited objectivity, in the form of
      instrumental means-end analysis. His methodology was coherent over time but
      gradually emerged when contemporary polemics called for his voice to be heard.

PMID- 10898892
TI  - Genetics of attention deficit/hyperactivity disorder: are we ready for molecular
      genetic studies?
AB  - Reports of possible genetic associations or linkages for attention deficit
      hyperactivity disorder are appearing at an increasing rate. As with many other
      neuropsychiatric disorders, claims of positive findings are frequently followed
      by negative reports. In this review, the evidence underpinning genetic hypotheses
      for the origins of ADHD is reviewed with particular emphasis on what is the
      heritable phenotype. It is concluded that advances in identifying mutations or
      allelic variations in genes predisposing to ADHD are likely, but the general
      replication of such findings must await a better characterization of the
      heritable phenotypic elements of ADHD and a better understanding of its genetic
      heterogeneity.

PMID- 10898893
TI  - Hypescheme: an operational criteria checklist and minimum data set for molecular
      genetic studies of attention deficit and hyperactivity disorders.
AB  - Investigators engaged in mapping the genetic basis of attention deficit
      hyperactivity disorder (ADHD) currently use a number of measures for the
      collection of clinical information. This gives rise to difficulties in comparing
      datasets and research communications between independent groups. This paper
      describes the development of Hypescheme, which is an operational criteria
      checklist for ADHD, oppositional defiant disorder (ODD), and conduct disorder
      (CD), and is proposed as a minimum dataset for those engaged in molecular genetic
      studies of ADHD. Hypescheme consists of a computerised data checklist system that
      includes all the operational criteria required for both DSM-IV and ICD-10
      diagnostic criteria and a systematic record of information about comorbid
      psychiatric, developmental, and neurological disorders. Using this data, an
      algorithm applies both DSM-IV and ICD-10 criteria to generate operational
      diagnostics under both these systems. Hypescheme is not designed to replace
      current assessment protocols but to be a final common checklist that can be
      completed by experienced researchers using all available data.

PMID- 10898894
TI  - Collaborative possibilities for molecular genetic studies of attention deficit
      hyperactivity disorder: report from an international conference.
AB  - Research on attention deficit hyperactivity disorder (ADHD) suggests that ADHD
      has a substantial genetic component. Although still in their infancy, molecular
      genetic studies have already implicated several genes as mediating susceptibility
      to ADHD. Nevertheless, given that ADHD's mode of inheritance is likely to be
      complex, much more work is needed to fully clarify the genetic architecture of
      the disorder. Because large samples and collaborative efforts will likely be
      needed to attain this goal, researchers in the field have convened a series of
      meetings to discuss measures for assessing ADHD, the feasibility of using common
      measures across sites, ways to increase communication among researchers, and
      strategies for defining genetically useful phenotypes.

PMID- 10898895
TI  - A haplotype relative risk study of the dopamine D4 receptor (DRD4) exon III
      repeat polymorphism and attention deficit hyperactivity disorder (ADHD).
AB  - Attention deficit hyperactivity disorder (ADHD) is a developmental syndrome
      expressed along three domains: inattention, hyperactive-impulsive, and combined
      type. Several investigations have recently examined the role of the dopamine DRD4
      exon III repeat polymorphism in ADHD. The long 7 repeat allele of this receptor
      was shown in three family-based studies, but not in one case control design, to
      be a risk factor for this disorder. We now report an additional family-based
      study of DRD4 exon III repeat region and ADHD. However, in the current study we
      fail to observe preferential transmission of the DRD4 exon III long 7 repeat
      allele, chi(2) = 0. 142, P < 0.1, df = 1. Nor was any preferential transmission
      observed when genotypes were compared, chi(2) = 0.180, P > 0.1, df = 1. Possible
      reasons are discussed, especially lack of sufficient power in analying more
      refined phenotypes, why the current results in contrast to previous findings fail
      to support a role for the long form of the DRD4 receptor as a putative risk
      factor for ADHD.

PMID- 10898896
TI  - Further evidence from haplotype analysis for linkage of the dopamine D4 receptor
      gene and attention-deficit hyperactivity disorder.
AB  - Several studies have suggested a possible association of a polymorphism at the
      dopamine D4 receptor gene and attention-deficit hyperactivity disorder [LaHoste
      et al., 1996; Rowe et al., 1998; Smalley et al., 1998; Sunohara et al.,
      submitted; Swanson et al., 1998]. The allele reported to be associated with
      attention-deficit hyperactivity disorder (ADHD) is the allele with seven copies
      of the 48 bp repeat in the third exon. We extend our study of the dopamine D4
      gene and ADHD by testing for linkage using two additional polymorphisms in the
      dopamine D4 receptor gene and a polymorphism in the closely linked gene, tyrosine
      hydroxylase. We also searched for two previously reported deletions, a 13 bp and
      a 21 bp deletion in the first exon. We examined the haplotypes of three
      polymorphisms of the D4 receptor gene and observed biased transmission of two of
      these haplotypes. Our findings further support the role of the dopamine D4 gene
      in ADHD.

PMID- 10898897
TI  - No association of the dopamine DRD4 receptor (DRD4) gene polymorphism with
      attention deficit hyperactivity disorder (ADHD) in the Irish population.
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent
      childhood-onset syndromes affecting 3%-6% of school-age children worldwide.
      Although the biological basis of ADHD is unknown, a dopaminergic abnormality has
      long been suggested. The dopamine D4 receptor gene (DRD4) has been mapped to
      chromosome 11p15.5 and has been implicated in predisposition to ADHD. Several
      independent genetic association studies have demonstrated increased frequency of
      the DRD4 7-repeat allele in ADHD cases compared with controls or excess
      transmission of the 7-repeat allele from parents to affected offspring. However,
      there have also been few negative studies. In this study we investigated 78 ADHD
      parent proband trios and 21 parent proband pairs for the transmission of the DRD4
      alleles in HHRR and case control design. We found no significant differences in
      the frequency of the DRD4 alleles transmitted or not transmitted to ADHD cases
      from their parents nor when comparing case allele frequencies to ethnically
      matched controls. Therefore, it is unlikely that the DRD4 7-repeat allele is
      associated with ADHD in the Irish population.

PMID- 10898898
TI  - Adult attention deficit hyperactivity disorder and the dopamine D4 receptor gene.
AB  - Attention deficit hyperactivity disorder (ADHD) is a prevalent psychiatric
      condition in children and follow up studies have indicated that 22-33% of
      patients continue to suffer from ADHD during late adolescence and adulthood.
      Convincing evidence supports the contribution of genetic factors in the etiology
      of ADHD, and the interaction of the psychostimulants with the dopamine system
      suggests that dopamine is involved in the pathophysiology. The 7-repeat allele of
      the 48 base pair repeat of the dopamine D4 receptor gene (DRD4) has been
      reported, with several replications, to be associated with ADHD in children. We
      tested for the presence of association between the DRD4 48 base repeat and adult
      ADHD in two independent samples: one comprised of cases and ethnically matched
      controls, and the second made up of nuclear families. Each case was assessed
      using a battery of adult ADHD assessment instruments. The analysis of the 66
      cases and 66 controls showed a significantly higher presence of the 7-repeat in
      the adult ADHD patients vs. controls (chi(2) = 5.65; df = 1; P = 0.01). In the
      analysis of transmission of DRD4 alleles in 44 nuclear families with the
      transmission disequilibrium test, a trend was observed toward a increased
      transmission of the 7-repeat from the heterozygous parents to the affected
      offspring (chi(2) = 2.00; df = 1; P = 0.15). When the two samples were combined,
      the overall significance was stronger (N = 110; z = 2.68; P = 0.003). The results
      of our study suggest a role of the 7-repeat allele in adult subjects suffering
      from ADHD. This finding is an important continuation of the group of studies that
      together strongly suggest the involvement of DRD4 in ADHD.

PMID- 10898899
TI  - Failure to replicate an excess of the long dopamine D4 exon III repeat
      polymorphism in ADHD in a family-based study.
AB  - The DRD4 exon III repeat polymorphism has been associated in adults with Novelty
      Seeking personality traits and in children with attention deficit hyperactivity
      disorder (ADHD) in some but not all studies. In a previous report we failed to
      observe preferential transmission of the long DRD4 repeat in ADHD compared to the
      haplotype relative risk (HRR) derived control group in a group of 49 triads (both
      parents and ADHD child) recruited in the Jerusalem area. In the current study we
      independently recruited an additional group of 49 triads from a different
      geographical location (Petak Tikvah) in Israel but having a similar ethnic
      background. In contrast to previous findings from a number of groups, in the
      current study an excess of the long DRD4 alleles was observed in the HRR control
      group compared to the ADHD subjects (Likelihood ratio = 5.50, P = 0. 02). In the
      expanded Israeli group of 98 triads so-far examined for the DRD4 repeat
      polymorphism there is an excess of the long alleles in the HRR control group
      (Likelihood ratio = 3.81, P = 0.05). These results attest to the complexity of
      ADHD inheritance and the likelihood that genetic heterogeneity characterizes this
      disorder especially across ethnic and cultural boundaries.

PMID- 10898900
TI  - No association between catechol-O-methyltransferase (COMT) gene polymorphism and
      attention deficit hyperactivity disorder (ADHD) in an Irish sample.
AB  - Pharmacological and biochemical studies have indicated that imbalances in
      dopaminergic transmission may contribute to the aetiology of attention deficit
      hyperactivity disorder (ADHD). The enzyme catechol-O-methyltransferase (COMT)
      plays a key role in the degradation of catecholamines such as dopamine, L-DOPA,
      adrenaline, and noradrenaline and therefore could be considered as a candidate
      locus for ADHD susceptibility. We hypothesised that a proportion of the genetic
      susceptibility to ADHD may be a consequence of dopamine depletion in the synapses
      due to high-level activity of the COMT gene (allele 1). Using the haplotype-based
      haplotype relative risk method and 94 affected children and their parents
      genotyped for COMT alleles, we found no significant differences in the frequency
      of the transmitted and nontransmitted alleles to ADHD cases from their parents.
      The absence of association between COMT alleles and ADHD indicated that this
      locus does not play a significant role or at least a role independent of other
      genes, in predisposing to ADHD in the Irish population.

PMID- 10898901
TI  - No association between low- and high-activity catecholamine-methyl-transferase
      (COMT) and attention deficit hyperactivity disorder (ADHD) in a sample of Turkish
      children.
AB  - Biochemical and genetic studies of attention deficit hyperactivity disorder
      (ADHD) suggest that regulation of catecholamine neurotransmission is a key factor
      in the aetiology of the disorder. In particular, it is postulated that an
      underactive dopamine system is associated with the disorder. In this study we
      have tested this hypothesis by screening a clinical sample of Turkish children
      with the combined subtype of ADHD with a functional variant of catecholamine
      methyl-transferase (COMT) that codes for high- and low-activity variants of the
      enzyme. Using within-family tests of association and linkage in a sample of 72
      children, we found no evidence for a genetic association or linkage. We conclude
      that altered regulation of catecholamines due to this polymorphism does not have
      a significant main effect on the risk for ADHD in this population. However, it
      remains feasible that more minor effects or interacting effects with other genes
      or environment exist.

PMID- 10898902
TI  - Association between attention deficit hyperactivity disorder and the DXS7 locus.
AB  - Attention deficit hyperactivity disorder (ADHD) is a prevalent disorder in
      children. The etiology of this disease is not clear. Genetics studies have
      suggested the involvement of the dopamine DRD-4 receptor gene and dopamine
      transporter gene (DAT1). Clinical studies have shown that monoamine oxidase-B
      (MAO-B) inhibitors are effective in the treatment of ADHD. These findings suggest
      that monoamine oxidase (MAO) genes might be involved in the origin of ADHD. In
      the present work, the DXS7 locus of chromosome X, which is closely linked to MAO
      genes, was selected as a marker to study the possible association between ADHD
      and MAO genes in the Chinese population. Haplotype-based haplotype relative risk
      (HHRR) and the transmission disequilibrium test (TDT) methods were employed to
      analyze the association and the linkage disequilibrium, respectively. Significant
      association (X(2) = 15.86; 1 df; P < 0.001) and linkage (X(2) = 14.88; 1 df; P <
      0.001) were detected between the 157-bp allele of the DXS7 locus and the DSM-III
      R-diagnosed ADHD (N = 72) in trios composed of father, mother, and affected
      offspring. The data suggested that ADHD was associated and in linkage with DXS7
      locus.

PMID- 10898903
TI  - Twin study of the etiology of comorbidity between reading disability and
      attention-deficit/hyperactivity disorder.
AB  - This study utilized a sample of 313 eight- to sixteen-year-old same-sex twin
      pairs (183 monozygotic, 130 dizygotic) to assess the etiology of comorbidity
      between reading disability (RD) and attention-deficit/hyperactivity disorder
      (ADHD). RD was assessed by a discriminant function score based on the Peabody
      Individual Achievement Test, a standardized measure of academic achievement. The
      DSM-III version of the Diagnostic Interview for Children and Adolescents was used
      to assess symptoms of ADHD, and separate factor scores were computed for
      inattention and hyperactivity/impulsivity (hyp/imp). Individuals with RD were
      significantly more likely than individuals without RD to exhibit elevations on
      both symptom dimensions, but the difference was larger for inattention than
      hyp/imp. Behavior genetic analyses indicated that the bivariate heritability of
      RD and inattention was significant (h(2)(g(RD/Inatt)) = 0.39), whereas the
      bivariate heritability of RD and hyp/imp was minimal and nonsignificant
      (h(2)(g(RD/Hyp)) = 0.05). Approximately 95% of the phenotypic covariance between
      RD and symptoms of inattention was attributable to common genetic influences,
      whereas only 21% of the phenotypic overlap between RD and hyp/imp was due to the
      same genetic factors.

PMID- 10898904
TI  - The TaqI A1 allele of the dopamine D2 receptor gene and alcoholism in Brazil:
      association and interaction with stress and harm avoidance on severity
      prediction.
AB  - Allele and genotype frequencies of the TaqI A polymorphism of dopamine D2
      receptor (DRD2) gene were compared in 115 alcohol-dependent Brazilian males and
      114 ethnically matched controls. Regression analyses were performed to test for
      an interactive effect between the DRD2 TaqI A1 allele and measures of stress and
      harm avoidance on severity of alcoholism and number of antisocial personality
      symptoms. A slightly positive association of DRD2 TaqI A1 genotypes with
      alcoholism was observed, by standard and molecular heterosis approaches. The DRD2
      TaqI A1 allele showed significant interaction with stress and harm avoidance in
      predicting the severity of physiologic dependence, and with harm avoidance for
      the number of antisocial personality symptoms. Separate partial correlation
      analyses showed that stress-related variables were significantly correlated with
      severity scores in alcoholics with the allele, but not in those without it. This
      is the first demonstration of an interaction between a genetic polymorphism and
      stress-related measures on the severity of psychiatric disorders.

PMID- 10898905
TI  - Alzheimer's disease and 5-HTTLPR polymorphism of the serotonin transporter gene:
      no evidence for an association.
AB  - Recently two independent research groups consistently reported a significant
      association between the serotonin transporter (5-HTT) gene and late-onset
      sporadic Alzheimer's disease (AD). They found that the "short" allele of the 5
      HTT gene-linked polymorphic region (5-HTTLPR), which is associated with reduced
      transcriptional activity of the gene, increases the risk of developing late-onset
      AD. The present study tried to replicate this finding in a Japanese sample. We
      genotyped 41 patients with early-onset AD (<65 years), 82 with late-onset AD, and
      336 controls. There was no significant difference in genotype or allele
      distribution between either patient group and controls in our sample, suggesting
      that the 5-HTTLPR does not play a major role in the pathogenesis of AD in
      Japanese.

PMID- 10898906
TI  - Association study of the tryptophan hydroxylase gene and bipolar affective
      disorder using family-based internal controls.
AB  - The tryptophan hydroxylase (TPH) gene encodes for the rate-limiting enzyme of the
      serotonin metabolism and, therefore, has to be considered a major candidate for
      association studies in affective disorders. Recently, an association between this
      gene and bipolar affective disorder has been reported in a French population. We
      sought to replicate this finding in a German sample. Allele frequencies of a
      biallelic polymorphism (A218C) of the TPH gene were determined in 95 bipolar I
      patients and their parents. Preferential transmission of alleles from
      heterozygous parents to bipolar offspring was tested with the "transmission
      disequilibrium test" (TDT), which eliminates the contribution of population
      stratification to an association finding. Our sample yielded a power >90% to
      detect the originally reported effect. Neither allele 218A nor allele 218C were
      preferentially transmitted from heterozygous parents to bipolar offspring. Our
      results, therefore, do not support the hypothesis that the TPH gene is involved
      in the etiology of bipolar disorder.

PMID- 10898907
TI  - Female with autistic disorder and monosomy X (Turner syndrome): parent-of-origin
      effect of the X chromosome.
AB  - We have ascertained and examined a patient with autistic disorder (AD) and
      monosomy X (Turner syndrome). The patient met Diagnostic and Statistical Manual
      of Mental Disorders (DSM-IV)/International Classification of Diseases (ICD-10)
      criteria for AD verified by the Autism Diagnostic Interview-Revised. The patient
      exhibited both social and verbal deficits and manifested the classical physical
      features associated with monosomy X. Skuse et al. [1997: Nature 387:705-708]
      reported three such cases of AD and monosomy X in their study of Turner syndrome
      and social cognition. They observed that monosomy X females with a maternally
      inherited X chromosome had reduced social cognition when compared with monosomy X
      females with a paternally inherited X chromosome. All three cases of AD and
      monosomy X were maternally inherited. Based on their data, they suggested that
      there was a gene for social cognition on the X chromosome that is imprinted and
      not expressed when the X chromosome is of maternal origin. Thus, we conducted
      parent-of-origin studies in our AD/monosomy X patient by genotyping X chromosome
      markers in the patient and her family. We found that the patient's X chromosome
      was of maternal origin. These findings represent the fourth documented case of
      maternal inheritance of AD and monosomy X and provide further support for the
      hypothesis that parent-of-origin of the X chromosome influences social cognition.

PMID- 10898908
TI  - Analysis of the pseudoautosomal X-linked gene SYBL1in bipolar affective disorder:
      description of a new candidate allele for psychiatric disorders.
AB  - The absence of father-to-son transmission has been observed in a subset of
      families with bipolar disorder (BPD), suggestive of a susceptibility gene on the
      sex-linked portion of the X chromosome. This is supported by some genetic linkage
      studies that have provided evidence for a susceptibility locus near Xq28. We have
      analyzed one candidate gene on Xq28, SYBL1, which maps to the Xq pseudoautosomal
      region (PAR). SYBL1 encodes a member of the synaptobrevin family of proteins that
      is involved in synaptic vesicle docking and membrane transport. Genes in the PAR
      generally escape X-chromosome inactivation and have an active homolog on the Y
      chromosome, which would result in an increase in same-sex concordance in paternal
      transmitted traits. However, SYBL1 is neither expressed on the Y chromosome nor
      the inactive X chromosome and would therefore be expected to show typical sex
      linked transmission. We have screened SYBL1 for mutations that could be tested as
      candidate alleles in the development of BPD. Following single-strand conformation
      polymorphism (SSCP) analysis and DNA sequencing, four single nucleotide
      polymorphisms were detected: a silent mutation at codon 108, two intron mutations
      without any obvious biological significance, and a G-->C transversion in the
      polypyrimidine tract at the 3' splice acceptor site preceding exon 8. This
      polymorphism, which creates a perfect 16/16 stretch of pyrimidines, was analyzed
      in 110 patients with BPD not selected for sex-linked transmission and 119 control
      subjects. The results show a statistical trend toward an increase in the
      frequency of the C allele in males with BPD but not females. Males: chi(2) =
      3.46, 1 df, p =.06; Females: chi(2) =.20, 1 df, p =.66.

PMID- 10898909
TI  - Investigation of dopamine receptor (DRD4) and dopamine transporter (DAT)
      polymorphisms for genetic linkage or association to panic disorder.
AB  - Clinical and animal studies suggest a role for the neurotransmitter dopamine in
      anxiety states. In humans, one such condition is panic disorder, which is
      typified by recurrent panic attacks accompanied by anticipatory anxiety. Family,
      segregation, and twin studies imply a genetic component to the pathophysiology of
      panic disorder. In this study, we examined the genes for the D4 dopamine receptor
      (DRD4) and the dopamine transporter (DAT) using three common sequence
      polymorphisms. Two of these polymorphisms were in DRD4, a 12 base-pair
      insertion/deletion in exon 1 and a 48 base-pair repeat in exon 3, and the third
      was a 40 base-pair repeat in the 3' untranslated region of DAT. We employed a
      family-based design, using 622 individuals in 70 families, as well as 82
      haplotype relative risk "trios". Subjects were genotyped at the polymorphic loci,
      and the data were analyzed for genetic association and linkage. There were no
      significant differences in allele frequencies or occurrence of genotypes within
      the triads for any of the three polymorphisms. No significant linkage between the
      DRD4 or DAT polymorphisms and panic disorder was observed in the multiplex
      families, using a variety of simulations for dominant and recessive models of
      inheritance. However, LOD scores of approximately 1.1 and 1.05 were observed for
      the DAT and DRD4 exon 1 loci, respectively. The results reported here provide
      little support for the role of these polymorphisms in panic disorder.

PMID- 10898910
TI  - Association of smoking and personality with a polymorphism of the dopamine
      transporter gene: results from a community survey.
AB  - In studies that used mixed volunteer samples, Lerman et al. [1999: Health Psychol
      18:14-20] and Sabol et al. [1999: Health Psychol 18:7-13] reported on an
      association of smoking with a polymorphism of the dopamine transporter gene. We
      attempted to replicate this association in a nonvolunteer community sample of 861
      Caucasians. No associations were found with either smoking initiation or smoking
      cessation. Sabol et al. [1999] also reported on an association of the dopamine
      transporter polymorphism with the personality trait of novelty seeking. However,
      we failed to find any associations with a range of personality traits, including
      a scale of fun seeking that correlates with novelty seeking. These negative
      findings suggest that either the original associations are not replicable or that
      any association is very small.

PMID- 10898911
TI  - Failure to establish linkage on the X chromosome in 301 families with
      schizophrenia or schizoaffective disorder.
AB  - The hypothesis that a gene for susceptibility to psychosis (specifically in the X
      Y homologous class) is located on the sex chromosomes has been proposed. Such a
      gene would account for the excess of sex chromosome anomalous males and females
      in populations of patients with psychosis, a tendency towards concordance by sex
      within families, and sex differences associated with psychosis and its underlying
      brain pathology. In earlier studies we observed small positive LOD scores in
      Xp11, and in a more recent and larger cohort of 178 sibling pairs, a peak
      multipoint nonparametric LOD score of 1. 55 at the locus DXS8032 in Xq21. The
      present study with a new set of markers extended the cohort to 301 ill sibling
      pairs and their parents. Despite the increase in sample size, the LOD score did
      not increase. A peak NPL of 1.55 was observed at the locus DXS1068 in proximal
      Xp, a region remote from the previous report. Separating families into those who
      were more likely to have X chromosome inheritance (maternal with no male to male
      transmission) did not yield stronger findings. In spite of the evidence that
      psychosis is related to a sex-dependent dimension of cerebral asymmetry, it is
      concluded that no consistent linkage of schizophrenia to the X chromosome can be
      demonstrated. In the context of the general failure of replication of linkage in
      psychosis, the possibility that the genetic predisposition to psychosis is
      contributed to by epigenetic modification rather than variations in the
      nucleotide sequence has to be considered.

PMID- 10898912
TI  - Department of Veterans Affairs Cooperative Studies Program genetic linkage study
      of schizophrenia: ascertainment methods and sample description.
AB  - To help clarify the genetics of schizophrenia, the Department of Veterans Affairs
      Cooperative Studies Program has completed data collection for a genetic linkage
      study of schizophrenia. This article describes the methodological details of the
      data collection. Subsequent articles will describe the results of our genome
      scan, which is now in progress. The data collection protocol included the
      Diagnostic Interview for Genetic Studies, the Family Interview for Genetic
      Studies, a review of medical records, and the collection of blood for
      transformation into lymphoblast cell lines. Among relatives of schizophrenic
      probands, we assessed auditory attention and verbal memory with
      neuropsychological tests. Among the 166 families ascertained for the study, 143
      had a single affected sib-pair, 17 had three affected siblings, one had five
      affected siblings and five had two sets of affected siblings. There was a total
      of 216 affected sib-pairs in these families. Using the n-1 rule, these families
      contain 188 independent affected sib-pairs.

PMID- 10898913
TI  - Lack of association between the functional variant of the catechol-o
      methyltransferase (COMT) gene and early-onset alcoholism associated with severe
      antisocial behavior.
AB  - Addictive drugs, including ethanol, increase the brain's dopaminergic
      transmission, and catechol-o-methyltransferase (COMT) enzyme has a crucial role
      in dopamine inactivation. A common functional polymorphism in the COMT gene
      results in a three- to four-fold variation in enzyme activity. In a previous
      study, we found an association between type 1 (with late-onset but without
      prominent antisocial behavior) alcoholism and the low activity allele of the COMT
      gene. In this work we analyzed whether the COMT polymorphism has any effect on
      the development of type 2 (with early-onset and habitual impulsive violent
      behavior) alcoholism. The COMT genotype was determined in 62 impulsive violent
      recidivist offenders with early-onset (type 2) alcoholism, 123 late-onset
      nonviolent (type 1) alcoholics, and 267 race and gender-matched controls. The
      allele and genotype frequencies of these groups were compared with each other and
      also with previously published data from 3,140 Finnish blood donors. The type 2
      alcoholics did not differ from either the blood donors or the controls. The low
      activity (L) allele frequency was higher among type 1 alcoholics (chi(2) = 4.98,
      P = 0.026) when compared with type 2 cases. The odds ratio for type 1 alcoholism
      as compared with type 2 alcoholism for those subjects with the LL genotype versus
      the HH genotype was 3.0 (95% confidence interval 1.1-8.4, P = 0.017). The results
      suggest that COMT genotype has no major role in the development of early-onset
      alcoholism with severe antisocial behavior.

PMID- 10898914
TI  - Psychosocial impact of predictive testing for Huntington disease on support
      persons.
AB  - Although a support person is required by many centers during the predictive
      testing protocol for Huntington disease (HD), little is known about the
      psychosocial impact of predictive testing on persons serving in this role.
      Eighteen adults who were support persons during predictive HD testing in one HD
      testing center completed a semi-structured interview to describe their
      experiences. Participants also completed the Impact of Events Scale (IES) to
      assess perceptions of emotional distress regarding predictive testing and the
      State Anxiety Scale of the State Trait Anxiety Inventory (STAI) to assess anxiety
      regarding the interview. State anxiety scores were similar to normative values
      for working adults. Although support persons for individuals with a positive gene
      test scored higher on all measures of the IES than those who were support persons
      for persons with negative gene mutation results, these differences were not
      statistically significant. Support persons identified aspects of the protocol
      that did not fit their needs, perceived the testing process as extending into
      subsequent caregiving responsibilities when the test was positive, and were
      uninformed regarding specific caregiving issues for family members with the gene
      mutation. The impact of the testing experience appeared to be most intense for
      those support persons who were at-risk offspring of probands. Findings suggest
      that individual assessment of support person needs may allow more focused
      counseling of support persons during predictive genetic HD testing. Collaboration
      with health care providers may facilitate symptom management following testing.

PMID- 10898915
TI  - 5-HT2a receptor polymorphism gene in bipolar disorder and harm avoidance
      personality trait.
AB  - The purpose [corrected] of this study was to investigate the relationship between
      bipolar disorder and the harm avoidance personality trait (HA), and the genetic
      contribution of the polymorphic DNA variation T102C in exon 1 of 5-HTR2a
      (chromosome 13q14-21) in bipolar disorder and HA personality trait. Forty bipolar
      patients and 89 normal subjects completed the TPQ questionnaire and were
      genotyped for 5-HT2a. Bipolar patients scored higher than normal subjects on the
      HA dimension. However, no contribution of the 5-HTR2a polymorphism on the bipolar
      disorder or on the HA personality trait emerged. Despite the limited sample size,
      these results exclude a major effect of the 5-HTR2a polymorphism on bipolar
      disorder and HA personality trait but not a minor effect.

PMID- 10898916
TI  - Three probands with autistic disorder and isodicentric chromosome 15.
AB  - We have identified three unrelated probands with autistic disorder (AD) and
      isodicentric chromosomes that encompass the proximal region of 15q11.2. All three
      probands met the Diagnostic and Statistical Manual of Mental Disorders, fourth
      edition [DSM-IV; American Psychiatric Association, 1994], and International
      Classification of Diseases ( ICD-10) diagnostic criteria for AD, confirmed with
      the Autism Diagnostic Interview -Revised (ADI-R). Chromosome analysis revealed
      the following karyotypes: 47,XX,+idic(15)(q11.2), 47,XX, +idic(15) (q11.2), and
      47,XY,+idic(15)(q11.2). Haplotype analysis of genotypic maker data in the
      probands and their parents showed that marker chromosomes in all three instances
      were of maternal origin. Comparison of the clinical findings of the three AD
      probands with case reports in the published literature (N = 20) reveals a
      clustering of physical and developmental features. Specifically, these three
      probands and the majority of reported probands in the literature exhibited
      hypotonia (n = 13), seizures (n = 13), and delayed gross motor development (n =
      13). In addition, clustering of the following clinical signs was seen with
      respect to exhibited speech delay (n = 13), lack of social reciprocity (n = 11),
      and stereotyped behaviors (n = 12). Collectively, these data provide further
      evidence for the involvement of chromosome 15 in AD as well as present
      preliminary data suggesting a clustering of clinical features in AD probands with
      proximal 15q anomalies.

PMID- 10898917
TI  - Investigation of Turner syndrome in schizophrenia.
AB  - Both Turner syndrome and schizophrenia are relatively infrequent conditions.
      Consequently, individuals having both illnesses are rare. Previous reviews of sex
      chromosome abnormalities in schizophrenia have focused primarily on the presence
      of supernumerary X-chromosomes. After identifying two female patients with
      schizophrenia and Turner syndrome, we reevaluated the available literature that
      survey female schizophrenics for the presence of chromosomal abnormalities.
      Eleven patients with Turner syndrome were identified among 6,483 females with
      schizophrenia in non-case-report studies. These survey results indicate that
      Turner syndrome occurs approximately three-fold more frequently in schizophrenic
      females than in the general female population (P < 0.02). Including 6 other case
      reports and our 2 cases, a total of 19 females with both schizophrenia and Turner
      syndrome were reported. Interestingly, whereas most Turner syndrome patients have
      the 45,X karyotype, the majority (18/19) of women with both illnesses have a
      mosaic karyotype (P < 0.0002). Given the potential role of genes on the X
      chromosome in the pathogenesis of schizophrenia, the study of unique populations
      with abnormalities in this chromosome, such as women with Turner syndrome, may
      offer clues into this illness.

PMID- 10898918
TI  - Lack of linkage disequilibrium between serotonin transporter protein gene
      (SLC6A4) and bipolar disorder.
AB  - The serotonin transporter (5HTT) gene appears to be of particular interest as
      5HTT is the selective site of action of selective serotonin reuptake inhibitors
      (SSRIs) that successfully treat bipolar depression (BP). The 5HTT gene is located
      on chromosome 17q11.1-q12 and has a 44 bp deletion/insertion functional
      polymorphism in the promoter region (SLC6A4). Results from association studies on
      SLC6A4 and BP disorder are conflicting. The aim of the present study was to
      investigate for the presence of linkage disequilibrium between SLC6A4 and BP
      disorder. One hundred thirty-three Bipolar I or Bipolar II probands with their
      living parents were recruited. Diagnoses were assessed by the structured
      interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth
      edition [DSM-IV, American Psychiatric Association, 1994] (SCID-I). Genotyping was
      performed with standard procedures and data were analyzed using the Transmission
      Disequilibrium Test [TDT, Spielman et al., 1993: Am J Hum Genet 52: 506-516]. One
      hundred two triads were informative for the analysis. Each of the two alleles of
      the SLC6A4 was transmitted at the same rate to bipolar probands (chi(2) = 0.692,
      df = 1, P = NS). Thus, it appears unlikely that the SLC6A4 plays a fundamental
      role in the pathogenesis of BP disorder. However, further studies focusing on the
      role of the 5HTT gene in predicting the response to SSRIs in BP patients might be
      worthwhile.

PMID- 10898919
TI  - Complex segregation analysis of obsessive-compulsive disorder in 141 families of
      eating disorder probands, with and without obsessive-compulsive disorder.
AB  - Probands affected with eating disorders (ED) present a higher number of relatives
      affected with obsessive-compulsive disorders/tic disorders than a comparison
      population. Therefore, we hypothesized that ED and obsessive-compulsive disorder
      (OCD) might share the same biological liability, and that a single major gene
      might account for that liability. We tested this hypothesis by applying a complex
      segregation analysis to 141 families of probands affected with ED (89 with
      anorexia nervosa, restricting and binge-eating types, 52 with bulimia nervosa).
      Given the hypothesized relationship between OCD and genetic spectrum disorders,
      we considered these diagnoses as affected phenotype in relatives. In Italian ED
      families, ED and OCD followed a Mendelian dominant model of transmission. When
      probands were divided according to co-diagnosis of OCD, best fit in the subgroup
      of families of 114 probands without OCD co-diagnosis was for a Mendelian dominant
      model of transmission whereas a Mendelian additive model of transmission
      represented best fit in the subgroup of families of 27 probands with an OCD co
      diagnosis. Genetic transmission was not shown in those families where the only
      affected phenotype was ED. The existence of a Mendelian mode of genetic
      transmission within ED families supports the hypothesis that a common genetic
      liability could account for both ED and OCD.

PMID- 10898920
TI  - Linkage and family-based association study of schizophrenia and the synapsin III
      locus that maps to chromosome 22q13.
AB  - The human synapsin III gene (synapsin III) is a member of a neuron-specific
      phosphoprotein gene family involved in short-term neurotransmitter release. We
      mapped synapsin III to chromosomal region 22q13 (13.1-13.31) by fluorescence in
      situ hybridization, a region that has been identified as a potential
      schizophrenia susceptibility locus. The dinucleotide repeat marker D22S280
      located in intron 5 of synapsin III was genotyped in a linkage and family-based
      association study to assess the role of the synapsin III locus in the etiology of
      schizophrenia. In 12 pedigrees with periodic catatonia comprising 135
      individuals, we found exclusion of linkage of marker D22S280 using lod score
      analysis with autosomal dominant/recessive models as well as affected only LOD
      score methods with dominant/recessive models. In a family-based association study
      of 61 unrelated parent-offspring trios with schizophrenia (according to the the
      Diagnostic and Statistical Manual of Mental Disorders, fourth edition [DSM-IV,
      American Psychiatric Association, 1994]), we found no association of individual
      D22S280 alleles to disease. Results of a multiallelic transmission/disequilibrium
      test (TDT(max) = 3.00; P = 0.55) challenged the possibility that D22S280 alleles
      appear with DSM-IV schizophrenia more frequently than expected. In addition, no
      evidence for gender differences or parent-of-origin effects were found. Thus, the
      synapsin III locus at chromosome 22q13 is not likely to contain a schizophrenia
      susceptibility gene.

PMID- 10898921
TI  - Investigation of a candidate gene for schizophrenia on Xq13 previously associated
      with mental retardation and hypothyroidism.
AB  - Weak support for linkage of schizophrenia to proximal Xq has previously been
      reported. In addition, an increased prevalence of thyroid disorder has been noted
      in families of individuals with schizophrenia. Recently, a gene mapped to Xq13
      termed HOPA has been found to be associated with mental retardation,
      hypothyroidism, and depression and to function as a coactivator for the thyroid
      receptor. We therefore examined the HOPA gene in a group of 111 probands from a
      larger cohort of multiplex families with schizophrenia, several of whom (n = 53)
      also had a family history of hypothyroidism. Four males and two females were
      found with an alteration in exon 42 of the HOPA gene compared with 8/492 males
      and 18/471 females (942 X chromosomes) compared with consecutively screened
      newborns (chi(2) = 3.92, P < 0.05). However, when available family members of
      each of the probands with an exon 42 variation were subsequently screened, the
      mutation did not segregate with schizophrenia in three of five families, although
      all 6 probands with an exon 42 variation did have hypothyroidism in either
      themselves (n = 3) or their mothers (n = 3) (P < 0.008). These findings replicate
      prior findings demonstrating an association between HOPA polymorphisms and
      hypothyroidism. In addition, the increased frequency of HOPA variants in this
      population may also provide a genetic basis for the familial association of
      thyroid disease and schizophrenia.

PMID- 10898922
TI  - Histamine N-methyltransferase functional polymorphism: lack of association with
      schizophrenia.
AB  - Histamine is a central nervous system (CNS) neurotransmitter that has been
      implicated in the pathophysiology of schizophrenia. Histamine N-methyltransferase
      (HNMT) terminates the neurotransmitter actions of histamine in the mammalian CNS,
      and levels of HNMT activity in human tissues are controlled, in part, by
      inheritance. A common C314T polymorphism in the HNMT gene causes a Thr105Ile
      change in encoded amino acid. The T314 allele results in decreased levels of both
      HNMT enzyme activity and immunoreactive protein. There is also a polymorphic CA
      repeat in intron 5 of the HNMT gene. The frequencies of alleles for the
      functional C314T polymorphism and the polymorphic CA repeat were compared between
      171 schizophrenia cases and 171 ethnically matched controls to test for possible
      disease association. No significant difference was found between the two groups
      in the frequency of the T314 allele in patients with schizophrenia and controls
      (0.068 vs. 0.078, respectively). Allele frequencies for the polymorphic HNMT CA
      repeat also failed to show significant differences between cases and matched
      controls.

PMID- 10898923
TI  - Functional variant in the DRD2 receptor promoter region and subtypes of
      alcoholism.
AB  - Dopaminergic pathway genes are considered as candidate genes for several
      neuropsychiatric diseases including severe alcoholism. Since 1990, there have
      been numerous reports of conflicting association studies of the Taq I A allele of
      the dopamine D2 receptor (DRD2) gene and alcoholism. Functional and structural
      variations in candidate genes offer more direct evaluation of their role in the
      development of a disorder. To determine the role of such variations in the DRD2
      gene in the development of alcoholism subtypes, we screened a sample of 173
      alcoholics and 88 normal controls with the A-241G and -141C Ins/Del variations in
      the promoter region and C311G variation in exon 7 of the DRD2 gene. Comparison of
      alcoholics with normal controls for allele frequency differences of these three
      variations was negative. Allele frequency differences of the two variations in
      the promoter region between type II alcoholics, alcoholics with medical
      complications, and normal controls were not significant. There was linkage
      disequilibrium only between -141 Ins/Del and Taq I D polymorphisms. We conclude
      that the functional and structural variations in DRD2 gene do not play a major
      role in the development of alcoholism subtypes in our sample.

PMID- 10898924
TI  - Five missense variants in the amino-terminal domain of the glucocorticoid
      receptor: no association with puerperal psychosis or schizophrenia.
AB  - Steroid hormone administration causes behavior changes in many and psychosis in a
      few. The clinical features suggest that genetic variants of the glucocorticoid
      receptor or cofactors could produce susceptible subpopulations who react
      adversely to hormonal cascades. To investigate this possibility, coding and
      splice site sequences of the glucocorticoid receptor were scanned for single
      nucleotide polymorphisms in genomic DNA samples from 100 schizophrenics (86
      Caucasians and 14 African-Americans) and 40 Caucasians with puerperal psychosis.
      Five amino acid substitutions were found in the amino-terminal domain at
      frequencies of 0.6 to 3.8% in Caucasians: R23K, F29L, L112F, D233N, and N363S. In
      addition, four silent nucleotide changes were found: E22E, K293K, D677D, and
      N766N; a transversion in intron 4 occurred beyond the splice junction. None of
      these variants can be linked to these disorders at present. However, the N363S
      variant contributes a new potential phosphorylation site and has been associated
      with increased body mass and reduced bone mineral density [Huizenga et al.,
      1998], so it is possible that the other missense variants confer traits that
      currently are unrecognized. Comparisons to natural glucocorticoid receptor
      mutants in the familial glucocorticoid resistance syndrome and steroid resistant
      leukemias suggest that amino acid substitutions at highly conserved residues may
      cause severe functional defects and serious illness, while changes at less
      conserved sites produce lesser alterations and milder disease.

PMID- 10898925
TI  - Genetic polymorphism at the CLOCK gene locus and major depression.
AB  - Genetic analysis in both mouse and Drosophila has indicated that the product of
      the CLOCK gene is an essential component of a circadian rhythm timing system. A
      single nucleotide polymorphism (SNP), T3111C, in the 3' flanking region of the
      human CLOCK gene has been identified. Homozygotes or heterozygotes for the 3111C
      allele have been reported to have higher mean scores on a measure of evening
      preference for activity (vs. morning preference) than subjects homozygous for the
      3111T allele. Since major depression is hypothesized to be closely linked to
      circadian rhythms, we explored whether this polymorphism might be related to
      susceptibility to major depression. We also ascertained allele frequency in an
      African-American control population, to begin to evaluate population variation at
      this locus. CLOCK T3111C allele frequencies were determined in 280 European
      American (EA) subjects, 143 with a history of major depression and 137 screened
      controls, and in 58 African American (AA) screened control subjects, using a
      polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP)
      method. There was no significant difference between EA depressed and control
      subjects in allele frequency. There was a significant difference in allele
      frequency between EA and AA subjects, demonstrating a potential for population
      stratification. In none of these groups were significant deviations from Hardy
      Weinberg equilibrium found. The present data do not support an association
      between CLOCK gene alleles at the T3111C locus and major depression.

PMID- 10898926
TI  - No relationship between Taq1 a polymorphism of dopamine D(2) receptor gene and
      extrapyramidal adverse effects of selective dopamine D(2) antagonists,
      bromperidol, and nemonapride in schizophrenia: a preliminary study.
AB  - The relationship between Taq1 A polymorphism of dopamine D(2) receptor (DRD(2))
      gene and extrapyramidal adverse effects of bromperidol and nemonapride, which are
      both antipsychotic drugs with selective and potent DRD(2) antagonistic property,
      was investigated in Japanese schizophrenic inpatients. Twenty-seven patients were
      treated with bromperidol at 6 or 12 or 18 mg/day, while 25 patients were treated
      with nemonapride at 18 mg/day. The duration of treatment was 3 weeks. The A1 and
      A2 alleles were determined by PCR. The extrapyramidal adverse effects were
      assessed by the Udvalg for Kliniske Unders?ogelser side effects rating scale. Six
      patients were homozygous for the A1 allele, 27 were heterozygous for the A1 and
      A2 alleles, and 19 were homozygous for the A2 allele. There were no significant
      differences in the incidences or severity of extrapyramidal adverse effects
      between the patients with one or two A1 alleles and those with no A1 allele. The
      present study suggests that Taq1 A polymorphism is not related to the development
      of extrapyramidal adverse effects during acute phase of bromperidol and
      nemonapride treatments.

PMID- 10898927
TI  - Low incidence of myotonic dystrophy in Chinese Hans is associated with a lower
      number of CTG trinucleotide repeats.

PMID- 10898928
TI  - Peek-a-boo fragile sites? Not really.

PMID- 10898929
TI  - Peek-a-boo fragile site? Or a peek-a-boo paper?

PMID- 10898930
TI  - Autistic symptoms in isodicentric 15 syndrome: response to Wolpert et al.

PMID- 10898931
TI  - Update on chromosomal locations for psychiatric disorders: report of the interim
      meeting of chromosome workshop chairpersons from the VIIth World Congress of
      Psychiatric Genetics, Monterey, California, October 14-18, 1999.

PMID- 10898932
TI  - Mammalian sperm acrosome: formation, contents, and function.
AB  - Sperm-egg interaction is a carbohydrate-mediated species-specific event which
      initiates a signal transduction cascade resulting in the exocytosis of sperm
      acrosomal contents (i.e., the acrosome reaction). This step is believed to be a
      prerequisite which enables the acrosome-reacted spermatozoa to penetrate the zona
      pellucida (ZP) and fertilize the egg. Successful fertilization in the mouse and
      several other species, including man, involves several sequential steps. These
      are (1) sperm capacitation in the female genital tract; (2) binding of
      capacitated spermatozoa to the egg's extracellular coat, the ZP; (3) induction of
      acrosome reaction (i.e., sperm activation); (4) penetration of the ZP; and (5)
      fusion of spermatozoon with the egg vitelline membrane. This minireview focuses
      on the most important aspects of the sperm acrosome, from its formation during
      sperm development in the testis (spermatogenesis) to its modification in the
      epididymis and function following sperm-egg interaction. Special emphasis has
      been given to spermatogenesis, a complex process involving multiple molecular
      events during mitotic cell division, meiosis, and the process of spermiogenesis.
      The last event is the final phase when a nondividing round spermatid is
      transformed into the complex structure of the spermatozoon containing a well
      developed acrosome. Our intention is also to briefly discuss the functional
      significance of the contents of the sperm acrosome during fertilization. It is
      important to mention that only the carbohydrate-recognizing receptor molecules
      (glycohydrolases, glycosyltransferases, and/or lectin-like molecules) present on
      the surface of capacitated spermatozoa are capable of binding to their
      complementary glycan chains on the ZP. The species-specific binding event starts
      a calcium-dependent signal transduction pathway resulting in sperm activation.
      The hydrolytic and proteolytic enzymes released at the site of sperm-zona
      interaction along with the enhanced thrust of the hyperactivated beat pattern of
      the bound spermatozoon, are important factors in regulating the penetration of
      the zona-intact egg.

PMID- 10898933
TI  - Structure and expression of the human MEP1A gene encoding the alpha subunit of
      metalloendopeptidase meprin A.
AB  - The human genome contains several sequences that are similar to the MEP1A gene
      encoding the alpha subunit of metalloendopeptidase meprin A. We now report the
      first genomic structure for the human MEP1A gene that maps to chromosome 6p21.
      The gene spans approximately 45 kb and consists of 14 exons and 13 introns.
      Overall, about 6.7% (3 kb) of the MEP1A gene corresponds to the exon sequences.
      Tissue specificity of the MEP1A gene expression was examined by dot blot analysis
      of poly(A) RNA from 50 different human tissues. The MEP1A mRNA was detected for
      the first time in kidney and appendix in addition to colon and small intestine
      previously known to express the gene. The elucidated gene structure and tissue
      specific expression of the MEP1A gene set the stage for investigating regulation
      and function of the gene and related sequences in the human genome.

PMID- 10898934
TI  - Topology of catalytic portion of prostaglandin I(2) synthase: identification by
      molecular modeling-guided site-specific antibodies.
AB  - Prostaglandin I(2) synthase (PGIS) is an eicosanoid-synthesizing cytochrome P450,
      located in the endoplasmic reticulum (ER) membrane. The membrane topology of the
      catalytic portion of PGIS is still unknown. General models of the membrane
      topology of microsomal P450s have been proposed in two forms: (a) large part of
      the polypeptide exposed on the cytoplasmic side with an NH(2)-terminal membrane
      anchor to the ER membrane and (b) deep immersion of the polypeptide in the
      membrane, as described by J. P. Miller et al. (1996, Biochemistry 35, 1466-1474).
      We have characterized the membrane topology of catalytic portion of PGIS using
      molecular modeling-guided site-specific antibodies. A 3D working model of PGIS
      was constructed by homology modeling using P450(BM-3) crystal structure as a
      template (S. K. Shyue et al., 1997, J. Biol. Chem. 272, 3657-3662). Three
      hydrophilic peptides corresponding to different regions of the surface portion of
      PGIS with residues 109-127 (P109-127), 353-368 (P353-368), and 411-431 (P411-431)
      predicted from the model and an NH(2)-terminal hydrophobic peptide (residues 1
      28, P1-28) were synthesized and used to prepare site-specific antibodies. All
      three of the hydrophilic peptide antibodies have high titer and are specifically
      recognized human PGIS, as shown by binding assays and Western blot analysis. In
      contrast, the hydrophobic NH(2)-terminal peptide has a much lower titer binding
      to the PGIS protein. The overall arrangement of the PGIS polypeptide with respect
      to the endoplasmic reticulum (ER) membrane was examined by immunocytochemistry
      techniques in transiently transfected COS-1 cells with recombinant human PGIS
      cDNA and in ECV cells expressing endogenous PGIS. The immunofluorescence staining
      for the cells with selective permeabilization of the plasma membrane using
      streptolysin O indicated that all three of the hydrophilic peptide antibodies
      bound to the cytoplasmic surface of the ER membrane. These results provide direct
      experimental evidence supporting the predicted 3D protein topological model in
      which the segments are located on the protein surface and the membrane
      topological model in which PGIS is largely exposed on the cytoplasmic side of the
      ER membrane. It also led us to conclude that the PGIS substrate, prostaglandin
      H(2) (PGH(2)), produced by prostaglandin H(2) synthase (PGHS) in the ER lumenal
      side must pass through the ER membrane barrier to the catalytic site of the PGIS
      in the cytoplasmic side of the ER membrane.

PMID- 10898935
TI  - Ubiquitin-specific proteases from Arabidopsis thaliana: cloning of AtUBP5 and
      analysis of substrate specificity of AtUBP3, AtUBP4, and AtUBP5 using Escherichia
      coli in vivo and in vitro assays.
AB  - A cDNA for a new ubiquitin-specific protease (UBP), AtUBP5, was identified from
      Arabidopsis thaliana flower mRNA using an oligonucleotide made against the
      conserved UBP cysteine (Cys) box. The 924-amino-acid AtUBP5 contains the regions
      characteristic of all UBPs and has 35% identity and 53% similarity overall to a
      mammalian UBP (Unp), resulting from additional significant similarity outside
      these regions. AtUBP5 has 48% identity and 58% similarity overall to two
      uncharacterized Arabidopsis genomic sequences but is distinct outside the UBP
      conserved regions from two other previously published Arabidopsis UBPs, AtUBP3
      and -4. Using in vivo Escherichia coli assays, which allow co-expression of
      GSTAtUBPs and substrates, we show that all three UBPs were active. AtUBP5 was
      active without 311 amino acids N-terminal to the active site cysteine, or without
      233 nonconserved amino acids between the Cys and His boxes, or without both,
      indicating the core region was sufficient. In in vivo and in vitro assays,
      GSTAtUBP3, -4, and -5 exhibited preference for specific Ub-Ub linkages,
      suggesting accessibility and/or conformation is important and demonstrating that
      these enzymes cleave post-translationally. A chimeric UBP consisting of the
      AtUBP5 Cys box with AtUBP3 amino acids was active and exhibited AtUBP3
      specificity, indicating that the modular nature of UBPs and specificity for
      cleavage sites is not determined by the Cys box.

PMID- 10898936
TI  - Evidence that the interaction between insulin-like growth factor (IGF)-II and IGF
      binding protein (IGFBP)-4 is essential for the action of the IGF-II-dependent
      IGFBP-4 protease.
AB  - A variety of human cell types, including human osteoblasts (hOBs), produce an
      IGFBP-4 protease, which cleaves IGFBP-4 in the presence of IGF-II. Recently, the
      pregnancy-associated plasma protein (PAPP)-A has been determined to be the IGF-II
      dependent IGFBP-4 protease produced by human fibroblasts. This study sought to
      define the mechanism by which IGF-II enhances IGFBP-4 proteolysis. Addition of
      PAPP-A antibody blocked the IGFBP-4 proteolytic activity in hOB conditioned
      medium (CM), suggesting that PAPP-A is the major IGFBP-4 protease in hOB CM. Pre
      incubation of IGFBP-4 with IGF-II, followed by removal of unbound IGF-II, led to
      IGFBP-4 proteolysis without further requirement of the presence of IGF-II in the
      reaction. In contrast, prior incubation of the partially purified IGFBP-4
      protease from either hOB CM or human pregnancy serum with IGF-II did not lead to
      IGFBP-4 proteolysis unless IGF-II was re-added to the assays. To further confirm
      that the interaction between IGF-II and IGFBP-4 is required for IGFBP-4 protease
      activity, we prepared IGFBP-4 mutants, which contained the intact cleavage site
      (Met135-Lys136) but lacked the IGF binding activity, by deleting the residues
      Leu72-His74 in the IGF binding domain or Cys183-Glu237 that contained an IGF
      binding enhancing motif. The IGFBP-4 protease was unable to cleave these IGFBP-4
      mutants, regardless of whether or not IGF-II was present in the assay.
      Conversely, an IGFBP-4 mutant with His74 replaced by an Ala, which exhibited
      normal IGF binding activity, was effectively cleaved in the presence of IGF-II.
      Taken together, these findings provided strong evidence that the interaction
      between IGF-II and IGFBP-4, rather than the direct interaction between IGF-II and
      IGFBP-4 protease, is required for optimal IGFBP-4 proteolysis.

PMID- 10898937
TI  - Testis glutathione peroxidase and phospholipid hydroperoxide glutathione
      peroxidase activities in aminoguanidine-treated diabetic rats.
AB  - Severe steroidogenic and spermatogenic alterations are reported in association
      with diabetic manifestations in humans and experimental animals. This study was
      planned to determine whether oxidative stress is involved in diabetes-induced
      alterations in the testes. Diabetes was induced in male rats by injection of 50
      mg/kg of streptozotocin (STZ). Ten weeks after injection of STZ, levels of
      selenium and activities of selenium dependent-glutathione peroxidase (GPx) and
      phospholipid hydroperoxide glutathione peroxidase (PHGPx) were measured in rat
      testis. Lipid and protein oxidations were evaluated as measurements of testis
      malondialdehyde (MDA) and protein carbonyl levels, respectively. Testis sulfydryl
      (SH) levels were also determined. The control levels of GPx and PHGPx activities
      were found to be 46.5 +/- 6.2 and 108.8 +/- 19.8 nmol GSH/mg protein/min,
      respectively. Diabetes caused an increase in testis GPx (65.0 +/- 21.1) and PHGPx
      (155.9 +/- 43.1) activities but did not affect the levels of selenium or SH.
      However, the testis MDA and protein carbonyl levels as markers of lipid and
      protein oxidation, respectively, did not increase in the diabetic group.
      Aminoguanidine (AG) treatment of diabetic rats returned the testis PHGPx activity
      (136.5 +/- 24.9) to the control level but did not change the value of GPx
      activity (69.2 +/- 17.4) compared with diabetic group. MDA and protein carbonyl
      levels in testis were not affected by AG treatment of diabetic rats, but
      interestingly AG caused SH levels to increase. The results indicate that reactive
      oxygen radicals were not involved in possible testicular complications of
      diabetes because diabetes-induced activations of GPx and PHGPx provided
      protection against oxidative stress, which was reported to be related to some
      diabetic complications.

PMID- 10898938
TI  - adapt78 protects cells against stress damage and suppresses cell growth.
AB  - We have previously identified several genes whose RNA products are induced in HA
      1 hamster cells under conditions where a cytoprotective adaptive response is
      observed. One of these genes, designated adapt78, was found to have a human
      homolog with some homology to glucose-regulated protein 78 (Grp78). We
      subsequently determined that adapt78 and grp78 mRNAs are induced by the same
      stress agents and conclude that adapt78 is a stress-response gene and putative
      new member of the grp stress gene family. Here we extend these studies to assess
      the effect of overexpressing adapt78 on stress protection and growth arrest. HA-1
      cells stably transfected with adapt78 cDNA were found to exhibit significantly
      reduced calcium- and hydrogen peroxide-mediated cytotoxicity as compared with
      control transfectants. In addition, adapt78 stable overexpressors exhibited
      significantly reduced cell growth. Both cytoprotection and growth arrest
      accompanied only modest overexpression of adapt78. Flow cytometry revealed that
      the growth arrest occurred in G(1)-phase. Immunoflourescent analysis revealed
      that Adapt78 protein exhibits significant perinuclear staining suggestive of
      endoplasmic reticulum localization in addition to cytoplasmic localization. These
      data indicate that adapt78 is both cytoprotective and growth suppressive and that
      these effects may be mediated by Adapt78 protein at the endoplasmic reticulum.

PMID- 10898939
TI  - Effect of cigarette smoke on salivary proteins and enzyme activities.
AB  - Exposure of human plasma in vitro to gas-phase cigarette smoke (CS) causes a
      marked modification of plasma proteins as measured by protein carbonyl assay.
      Aldehydes present in CS may cause this elevation of protein carbonyls by reacting
      with sulfhydryl groups of proteins. Saliva is the first body fluid to confront
      the inhaled CS. Thus, in vitro exposure of saliva to nine "puffs" of CS also
      showed a distinct increase in protein carbonyls. Ascorbate and desferrioxamine
      mesylate had little effect on protein carbonyl formation, while GSH and N
      acetylcysteine considerably inhibited the accumulation of protein carbonyls due
      to CS exposure. Following the exposure to CS, the activities of several salivary
      enzymes-amylase, lactic dehydrogenase (LDH), and acid phosphatase-were found to
      be significantly reduced (34, 57, and 77%, respectively). However, CS had no
      effect on the activities of aspartate aminotransferase and alkaline phosphatase.
      Addition of 1 mM of GSH and N-acetylcysteine considerably protected LDH and
      amylase activities, suggesting that sulfhydryl groups are affected in LDH and
      amylase. On the other hand, addition of 1 mM ascorbate caused a further loss of
      LDH and amylase activities, which could be partially prevented by the addition of
      desferrioxamine mesylate, implicating metal-catalyzed oxidation processes.
      Finally, loss of acid phosphatase activity was completely unaffected by any of
      the above antioxidants. It is concluded that the loss of salivary enzyme
      activities may be due to various agents in the CS that affect the enzyme
      activities via different mechanisms.

PMID- 10898940
TI  - Secondary structure and calcium-induced folding of the Clostridium thermocellum
      dockerin domain determined by NMR spectroscopy.
AB  - Assembly of the cellulosome, a large, extracellular cellulase complex, depends
      upon docking of a myriad of enzymatic subunits to homologous receptors, or
      cohesin domains, arranged in tandem along a noncatalytic scaffolding protein.
      Docking to the cohesin domains is mediated by a highly conserved domain, dockerin
      (DS), borne by each enzymatic subunit. DS consists of two 22-amino-acid
      duplicated sequences, each bearing homology to the EF-hand calcium-binding loop.
      To compare the DS structure with that of the EF-hand helix-loop-helix motif, we
      analyzed the solution secondary structure of the DS from the cellobiohydrolase
      CelS subunit of the Clostridium thermocellum cellulosome using multidimensional
      heteronuclear NMR spectroscopy. The effect of Ca(2+)-binding on the DS structure
      was first investigated by using 2D (15)N-(1)H HSQC NMR spectroscopy. Changes in
      the spectra during Ca(2+) titration revealed that Ca(2+) induces folding of DS
      into its tertiary structure. This Ca(2+)-induced protein folding distinguishes DS
      from typical EF-hand-containing proteins. Sequential backbone assignments were
      determined for 63 of 69 residues. Analysis of the NOE connectivities and H(alpha)
      chemical shifts revealed that each half of the dockerin contains just one alpha
      helix, comparable to the F-helix of the EF-hand motif. Thus, the structure of the
      DS Ca(2+)-binding subdomain deviates from that of the canonical EF-hand motif.

PMID- 10898941
TI  - Acid phosphatase reaction with peroxyl radicals: inactivation mechanism and
      behavior of the partially modified ensemble.
AB  - Acid phosphatase (AP) is readily inactivated when exposed to the free radicals
      generated in the pyrolysis of 2, 2'-azobis(2-amidinopropane) hydrochloride (AAPH)
      under aerobic conditions. On average, a large number of tryptophan groups are
      modified by each protein molecule that loses its catalytic activity. In spite of
      this, the enzyme inactivation takes place without induction times, a result that
      indicates either that damage is progressive or that damage of a critical target
      is needed to inactivate the enzyme (all-or-nothing mechanism). A Lineweaver-Burk
      plot of the enzyme activity measured at pH 4.8 is not compatible with an all-or
      nothing mechanism, showing that after exposure of the native protein ensemble to
      the free radical source there are partially damaged molecules whose affinity for
      the substrate is widely different from that of the native molecules. On the other
      hand, the partially damaged ensemble shows a normal Michaelis-Menten behavior
      when the activity is measured at pH 7.0, with only a reduced value of V(M),
      relative to that of the unmodified ensemble. These results show that the native
      protein and modified proteins that remain active constitute different
      populations, with different responses to pH changes. Comparative heat
      denaturation studies of the native and pretreated proteins support this proposal.

PMID- 10898942
TI  - A new mechanism for the control of phenoloxidase activity: inhibition and complex
      formation with quinone isomerase.
AB  - Insect phenoloxidases participate in three physiologically important processes,
      viz., cuticular hardening (sclerotization), defense reactions (immune reaction),
      and wound healing. Arrest or even delay of any of these processes compromises the
      survival of insects. Since the products of phenoloxidase action, viz., quinones,
      are cytotoxic, uncontrolled phenoloxidase action is deleterious to the insects.
      Therefore, the activity of this important enzyme has to be finely controlled. A
      novel inhibition of insect phenoloxidases, which serves as a new regulatory
      mechanism for control of its activity, is described. The activity of
      phenoloxidases isolated from both Sarcophaga bullata and Manduca sexta is
      drastically inhibited by quinone isomerase (isolated from Calliphora), an enzyme
      that utilizes the phenoloxidase-generated 4-alkylquinones. In turn, phenoloxidase
      reciprocated the inhibition of isomerase. By forming a complex and controlling
      each other's activity, these two enzymes seem to regulate the levels of
      endogenously quinones. In support of this contention, an endogenous complex
      consisting of phenoloxidase, quinone isomerase, and quinone methide isomerase was
      characterized from the insect, Calliphora. This sclerotinogenic complex was
      isolated and purified by borate extraction of the larval cuticle, ammonium
      sulfate precipitation, and Sepharose 6B column chromatography. The complex
      exhibited a molecular mass of about 620-680 kDa, as judged by size-exclusion
      chromatography on Sepharose 6B and HPLC and did not even enter 3% polyacrylamide
      gel during electrophoresis. The phenoloxidase activity of the complex exhibited a
      wide substrate specificity. Incubation of the complex with N-acetyldopamine
      rapidly generated N-acetylnorepinephrine, dehydro-N-acetyldopamine, and its
      dimers. In addition, transient accumulation of N-acetyldopamine quinone was also
      observed. These results confirm the presence of phenoloxidase, quinone isomerase,
      and quinone methide isomerase in the complex. Attempts to dissociate the complex
      with even trace amounts of SDS ended in the total loss of quinone isomerase
      activity. The complex does not seems to be made up of stoichiometric amounts of
      individual enzymes as the ratio of phenoloxidase to quinone isomerase varied from
      preparation to preparation. It is proposed that the complex formation between
      sequential enzymes of sclerotinogenic pathway is advantageous for the organism to
      effectively channel various reactive intermediates during cuticular hardening.

PMID- 10898943
TI  - Noncompetitive, reversible inhibition of aminoacylase-1 by a series of L-alpha
      hydroxyl and L-alpha-fluoro fatty acids: ligand specificity of aspergillus oryzae
      and porcine kidney enzymes.
AB  - L-lactate and L-beta-phenyllactate have been identified in the culture broth of
      Streptomyces sp. KY-11 as reversible noncompetitive inhibitors of Aspergillus
      oryzae aminoacylase-1 and porcine kidney aminoacylase I. A series of alpha
      hydroxyl acids (DL-R-CH(OH)-COOH, R = Et, n-pro, n-butyl, n-pentyl, n-hexyl) also
      inhibited the two enzymes in reversible noncompetitive kinetics, and the
      inhibition potency (-log K(i)) increased with the increased hydrophobicity of the
      R group. The two eukaryotic enzymes showed distinct preferences to the ligand
      alpha-alkyl group, and the fungus enzyme was inhibited by L-beta-phenyllactate (R
      = benzyl) 10(3)-fold more potently than the mammalian enzyme. L-alpha-Fluoro-beta
      phenyl-propionate and its D-isomer were used to show that the L-configuration of
      the alpha-substituent was important for potent inhibition of both the enzymes.
      The fungus aminoacylase-1 steeply decreased the affinity to alpha-fluoro- and
      alpha-hydroxy-n-caproate as pH was raised from 7 to 11, whereas the mammalian
      enzyme retained the affinity to these ligands under alkaline conditions. These
      results suggest that A. oryzae aminoacylase-1 has an acidic residue that
      interacts with -OH or -F, while the mammalian enzyme would have a basic residue
      that recognizes the alpha-substituents.

PMID- 10898944
TI  - Ferredoxin-dependent iron-sulfur flavoprotein glutamate synthase (GlsF) from the
      Cyanobacterium synechocystis sp. PCC 6803: expression and assembly in Escherichia
      coli.
AB  - The unicellular cyanobacterium Synechocystis sp. PCC 6803 contains two different
      glutamate synthases whose genes, gltB and glsF (previously known as gltS), have
      been cloned (F. Navarro et al., 1995, Plant Mol. Biol. 27, 753-767). The glsF
      gene has been expressed in the glutamate auxotrophic Escherichia coli strain
      CLR207 RecA, but the corresponding protein does not complement the auxotrophy.
      The transformed strain showed ferredoxin-dependent glutamate synthase (Fd-GOGAT)
      activity, demonstrating the capability of E. coli for providing and correctly
      assembling both the iron-sulfur center and the flavin cofactor of the enzyme. Fd
      GOGAT (GlsF) is correctly cleaved at Cys37 to form the mature enzyme in E. coli,
      as occurs with the large subunit of its own NADPH-GOGAT. The recombinant Fd-GOGAT
      has been purified to electrophoretic homogeneity, using as the main purification
      step a ferredoxin-affinity chromatography. The pure enzyme, with a molecular mass
      of about 180 kDa, shows an absorption spectrum characteristic of iron-sulfur
      flavoproteins. The analyses of the prosthetic groups indicate that Fd-GOGAT
      contains only one FMN, but no FAD, and one [3Fe-4S](+,0) cluster per molecule.
      Oxidation-reduction titration, using absorbance changes of the FMN group in the
      visible region, gave a midpoint redox potential of -200 +/- 25 mV at pH 7.5. The
      recombinant enzyme is strictly ferredoxin-dependent and shows apparent K(M)
      values similar to those of the native Synechocystis protein: 4.5 vs 3.5 microM,
      2.2 vs 2.5 mM, and 0.6 vs 0.5 mM for ferredoxin, glutamine, and 2-oxoglutarate,
      respectively. The addition of the reductant dithionite to the enzyme resulted in
      the loss of the absorption peak at 436 nm, characteristic of oxidized flavins,
      which was restored by the anaerobic addition of 2-oxoglutarate, in the presence
      of glutamine.

PMID- 10898945
TI  - Enzyme activities leading to NAD synthesis in human lymphocytes.
AB  - Pyridine nucleotide levels and the activities of enzymes involved in NAD
      synthesis (nicotinic acid phosphoribosyltransferase, nicotinic acid- and
      nicotinamide mononucleotide-adenylyltransferase) have been assayed in human
      normal lymphocytes by an HPLC method using radioactive or nonradioactive
      substrates. NAD concentration was 46.4 +/- 17.2 pmol 10(-6) cells, and that of
      NADP was 14.5 +/- 3.9 pmol 10(-6) cells (mean +/- standard deviation). The
      adenylyltransferase activity using nicotinic acid mononucleotide as substrate was
      1.530 +/- 0.216 nmol h(-1) 10(-6) cells, using nicotinamide mononucleotide was
      1.466 +/- 0.354 nmol h(-1) 10(-6) cells. The apparent K(M) values were 0.015 mM
      for the former substrate and 0.167 mM for the latter. The mean activity of
      nicotinic acid phosphoribosyltransferase was 0.038 +/- 0.014 nmol h(-1) 10(-6)
      cells, and the apparent K(M) for nicotinic acid was 0.165 mM. The proposed
      methods, easy and rapid to perform, are reliable and sensitive, avoiding the use
      of radiolabels except for NAPRT and displaying a very low activity. The reported
      findings, together with the previous ones in human erythrocytes, can provide an
      useful base to investigate NAD metabolism in humans through the study of blood
      cells.

PMID- 10898946
TI  - Studies of L-arginine transport in bovine aortic endothelial cells.
AB  - We have previously demonstrated that p(1),p(4)-diadenosine 5'-tetraphosphate
      induces the release of NO and modulates the uptake of L-arginine by bovine aortic
      endothelial cells (BAEC) [Hilderman, R. H., and Christensen, E. F. (1998) FEBS
      Lett. 407, 320-324; Hilderman, R. H., Casey, T. E., and Pojoga, L. H. (2000)
      Arch. Biochem. Biophys. 375, 124-130]. In this communication we characterize the
      uptake of L-Arg by BAEC. L-Arg is transported into BAEC by at least two different
      transporter systems. One transporter system is protein synthesis dependent, and L
      Arg transported by this system is incorporated into proteins. The second
      transporter system involved in L-Arg uptake is protein synthesis independent, and
      uptake occurs by facilitated diffusion. The L-Arg transported by facilitated
      diffusion is metabolized into L-argininosuccinate. Homologous and heterologous
      competition uptake studies were performed using a fixed concentration of
      radiolabeled L-Arg, L-lysine, and L-leucine with varying concentrations of
      competing nonradiolabeled amino acids. The results of these competition uptake
      studies are consistent with the protein-synthesis-dependent uptake of L-Arg
      taking place through a transporter system that is highly specific for L-Arg and
      with the facilitated diffusion uptake taking place through a transporter that is
      specific for L-Arg and L-Leu.

PMID- 10898947
TI  - Methanococcus jannaschii ORF mj0608 codes for a class C inorganic pyrophosphatase
      protected by Co(2+) or Mn(2+) ions against fluoride inhibition.
AB  - Openreading frame mj0608 of the Methanococcus jannaschii genome, recognized by
      its sequence similarity to that of the gene coding for class C inorganic
      pyrophosphatase in Bacillus subtilis, was cloned and over-expressed in
      Escherichia coli. The protein was purified and characterized by SDS-PAGE, M(r),
      and N-terminal sequence. Under suitable conditions it catalyzed the specific
      hydrolysis of PPi at about 600 micromol x min(-1) x mg(-1) at 25 degrees C, and
      at 8000 micromol x min(-1) x mg(-1) at 85 degrees C. Therefore this protein is a
      specific inorganic pyrophosphatase. The activities of Mg(2+), Mn(2+), Co(2+), and
      Zn(2+) ions as cofactors for hydrolysis of PPi were compared at pH 7.5 and 9.0.
      Unlike the class C pyrophosphatase of B. subtilis, this enzyme required no prior
      activation by low concentrations of Mn(2+) or Co(2+) ions. However, prior
      exposure to these ions afforded striking protection against inhibition by sodium
      fluoride, to which the enzyme was otherwise very sensitive.

PMID- 10898948
TI  - Effect of light on phosphatidate phosphohydrolase activity of retina rod outer
      segments: the role of transducin.
AB  - The aim of the present paper is to evaluate the modulation of phosphatidate
      phosphohydrolase (PAPase) and diacylglyceride lipase (DGL) activities in bovine
      rod outer segment (ROS) under dark and light conditions and to evaluate the role
      of transducin (T) in this phenomenon. In dark-adapted ROS membranes exposed to
      light, PAPase activity is inhibited by 20% with respect to the activity found
      under dark conditions. To determine whether the retinal G protein, T,
      participates in the regulation of PAPase activity in these membranes, the effects
      of GTPgammaS and GDPbetaS on enzyme activity were examined. Under dark conditions
      in the presence of GTPgammaS, which stabilizes T in its active form (Talpha +
      Tbetagamma), enzyme activity was inhibited and approached control values under
      light conditions. GDPbetaS, on the other hand, which stabilizes the inactive
      state of T (Talphabetagamma), stimulated PAPase activity by 36% with respect to
      control light conditions. ADP-ribosylation by cholera and pertussis toxin was
      also studied. In ADP-rybosilated ROS membranes with pertussis toxin under dark
      conditions, PAPase activity was 36% higher than the activity found under control
      light conditions. ADP-ribosylation by CTx, on the other hand, inhibited PAPase
      activity by 22%, with respect to dark control conditions, mimicking light effect.
      The effects of GTPgammaS and GDPbetaS and conditions of ADP-ribosylation by PTx
      and CTx on DGL activity were similar to those of PAPase activities. Based on NEM
      sensitivity we have also demonstrated that the PAPase present in ROS is the PAP 2
      isoform. Our findings therefore suggest that light inhibition of PAP 2 in ROS is
      a transducin-mediated mechanism.

PMID- 10898949
TI  - Purification and characterization of glutamine:fructose 6-phosphate
      amidotransferase from rat liver.
AB  - The enzyme glutamine:fructose 6-phosphate amidotransferase (L-glutamine:D
      fructose-6-phosphate amidotransferase; EC 2.6.1.16, GFAT) catalyzes the formation
      of glucosamine 6-phosphate from fructose 6-phosphate and glutamine. In view of
      the important role of GFAT in the hexosamine biosynthetic pathway, we have
      purified the enzyme from rat liver and characterized its physicochemical
      properties in comparison to those from the published microbial enzymes. The
      purified enzyme has a molecular mass of about 75 kDa as determined by sodium
      dodecyl sulfate polyacrylamide gel electrophoresis. On a Sephacryl S-200 gel
      filtration column, the purified enzyme eluted in a single peak corresponding to a
      molecular mass of about 280 kDa, indicating that the active enzyme may be
      composed of four subunits. The N-terminal amino acid sequence of the purified
      enzyme was determined as X-G-I-F-A-Y-L-N-Y-H-X-P-R, where X indicates an
      unidentified residue. The K(M) values of the purified enzyme for fructose 6
      phosphate and glutamine were 0.4 and 0.8 mM, respectively. The purified enzyme
      was inactivated by 4, 4'-dithiodipyridine, and the activity of the inactivated
      enzyme was restored by dithiothreitol. The inactivation followed pseudo first
      order and saturation kinetics with the K(inact) of 5.0 microM. Kinetic studies
      also indicated that 4,4'-dithiodipyridine is a competitive inhibitor of the
      enzyme with respect to glutamine. Isolation and analysis of the cysteine-modified
      peptide indicated that Cys-1 was the modified site. Cys-1 has been suggested to
      play an important role in enzymatic activity of the Escherichia coli enzyme (M.
      N. Isupov, G. Obmolova, S. Butterworth, M. Badet-Denisot, B. Badet, I.
      Polikarpov, J. A. Littlechild, and A. Teplyakov, 1996, Structure 4, 801-810).

PMID- 10898950
TI  - Reaction of phenylaminoethyl selenides with peroxynitrite and hydrogen peroxide.
AB  - Peroxynitrite, a reactive cytotoxic species generated by the reaction of
      superoxide with nitric oxide, rapidly oxidizes phenylaminoethyl selenide (PAESe)
      and its para-substituted derivatives with second-order rate constants ranging
      from 900 to 3000 M(-1) s(-1) at neutral pH (pH 7.0) and 25 degrees C. These
      values are approximately 3 x 10(4) times greater than the corresponding rate
      constants for the reactions of selenides with hydrogen peroxide. The
      peroxynitrite reaction was also studied at alkaline pH. HPLC analysis confirms
      that both the peroxynitrite and hydrogen peroxide reactions produced the
      corresponding phenylaminoethyl selenoxide (PAESeO) as the sole selenium
      containing product, with a stoichiometry of 1 mol of PAESe oxidized per 1 mol of
      PAESeO formed per 1 mol of oxidant reacted. The influence of para-substituents on
      the rate constants was investigated using Hammett plots; in both cases the data
      are consistent with an S(N)2-type mechanism, wherein the selenium atom acts as
      the nucleophile. Our results provide further evidence that organoselenium
      compounds may play a protective role in the defense against the many reactive
      oxidizing species produced in cellular metabolism.

PMID- 10898951
TI  - CYP2E1 degradation by in vitro reconstituted systems: role of the molecular
      chaperone hsp90.
AB  - One major mode of regulation of cytochrome P450 2E1 (CYP2E1) is at the
      posttranscriptional level, since many low-molecular-weight compounds stabilize
      the enzyme against proteolysis by the proteasome complex. In an in vitro system
      containing human liver microsomes, degradation of CYP2E1 in the microsomes
      required addition of the human liver cytosol fraction in a reaction sensitive to
      inhibitors of the proteasome complex. It is not clear how CYP2E1 in the
      microsomal membrane becomes accessible to the cytosolic proteasome. Since
      molecular chaperones play a role in protein folding and degradation, the possible
      role of heat shock proteins in CYP2E1 degradation by this reconstituted system
      was evaluated. Degradation of CYP2E1 required ATP; ATP-gammaS, a nonhydrolyzable
      analogue of ATP, did not catalyze CYP2E1 degradation by the cytosol fraction,
      indicating that ATP hydrolysis is required. Geldanamycin, a specific inhibitor of
      hsp90, inhibited the degradation of microsomal CYP2E1 by the cytosol fraction.
      Control experiments indicated that geldanamycin was not a substrate/ligand of
      CYP2E1 nor did it prevent microsomal lipid peroxidation, a process which
      increases CYP2E1 turnover. Inhibition by geldanamycin was prevented by molybdate.
      Both of these compounds have been shown to promote alterations in hsp90 structure
      and to modulate hsp90-protein interactions. The proteasome activity in the
      cytosol, as assayed by the cleavage of a fluorogenic peptide, was enhanced when
      ATP was added and inhibited by 30-40% by geldanamycin, effects that are similar,
      although less pronounced, to the degradation of CYP2E1 by the cytosol. Purified
      20S proteasome could catalyze degradation of CYP2E1; however, in an assay using
      equal peptidase activity, the cytosol fraction was much more effective than the
      20S proteasome in promoting CYP2E1 degradation. Immunodepletion of hsp90 from the
      cytosol resulted in prevention of the degradation of CYP2E1, a reaction that was
      reversed by the addition of pure hsp90 to this cytosol. These results suggest
      that in addition to the proteasome, the cytosol fraction contains other factors
      that modulate the efficiency of CYP2E1 degradation. The sensitivity to
      geldanamycin and molybdate and the immunodepletion experiments suggest that hsp90
      is one of these factors that interact with CYP2E1 and/or with the proteasome to
      promote the degradation of this microsomal P450.

PMID- 10898952
TI  - The heme-containing N-fragment (residues 1-56) of cytochrome c is a bis-histidine
      functional system.
AB  - The structural and redox properties of a heme-containing fragment (1-56 residues)
      of cytochrome c have been investigated by spectroscopic (circular dichroism,
      electronic absorption, and EPR) and voltammetric techniques. The results indicate
      that the N-fragment lacks ordered secondary structure and has two histidines
      axially bound to the heme-iron (the native His18 and a misligated His26 or
      His33). Despite the absence of ordered secondary structure, the peptide chain
      shields the heme group from solvent, as shown by (i) the pK(a) of protonation of
      the nonnative histidine ligand (5.18 +/- 0.05), lower than that of the bis
      histidine guanidine-unfolded cytochrome c (5.58 +/- 0.05), and (ii) the redox
      potential, E(o) = 0 +/- 5 mV versus NHE, close to that of bis-histidine
      cytochrome c mutants but less negative than that of bis-histidine complexes of
      microperoxidase with short peptides. The electroactive N-fragment may be taken as
      a "minichrome c" model, with interesting potential for application to biosensor
      technology; further, the system provides useful information for a deeper
      understanding of cytochrome c folding and structural/functional organization.

PMID- 10898953
TI  - Caspase-mediated proteolytic activation of calcineurin in thapsigargin-mediated
      apoptosis in SH-SY5Y neuroblastoma cells.
AB  - We previously demonstrated a loss in calmodulin (CaM)-dependent protein kinase
      activity in SH-SY5Y cells undergoing thapsigargin-mediated apoptosis, (K. M.
      McGinnis et al., 1998, J. Biol. Chem. 273, 19993-20000). Here we demonstrate that
      the large subunit of the CaM-dependent protein phosphatase 2B (calcineurin) is
      fragmented during SH-SY5Y cell apoptosis to a major fragment of 45 kDa in a
      caspase inhibitor-sensitive manner. A 45-kDa fragment was also produced when
      purified calcineurin was digested with recombinant caspase-3. The major cleavage
      site was identified to be DFGD* G(386)ATAA, which removes the C-terminal CaM
      binding and autoinhibitory regions from the catalytic domain. Phosphatase
      activity increased progressively with caspase-3 digestion, coupled with the
      eventual loss of CaM-dependency. Calcineurin-mediated dephosphorylation of NFATc
      was also detected in thapsigargin-treated cells. Last, calcineurin inhibitors
      FK506 and cypermethrin provided partial protection against thapsigargin-mediated
      apoptosis, suggesting that calcineurin overactivation contributes to thapsigargin
      induced apoptosis.

PMID- 10898954
TI  - Mechanism of selective release of membrane proteins from human erythrocytes in
      the presence of liposomes.
AB  - Incubation of erythrocytes with liposomes results in the release of shed vesicles
      rich in glycosyl-phosphatidylinositol (GPI)-anchored proteins but poor in
      transmembranous proteins. We investigated the mechanisms of membrane protein
      polarization by examining the effect of the interaction between spectrin and
      membrane proteins on the release of a transmembranous protein, band 3, and a GPI
      anchored protein, acetylcholinesterase (AChE), from erythrocyte ghosts.
      Polymerization of spectrin resulted in a 30-fold decrease in the released amount
      of band 3 per constant amount of shed vesicles but did not affect the amount of
      released AChE per constant amount of shed vesicles. On the other hand, the amount
      of released band 3 per constant amount of shed vesicles increased by cleaving the
      cytoplasmic part of band 3. Our results first demonstrated that the diffusibility
      of membrane proteins determined by steric hindrance between membrane proteins and
      protein mesh primarily determines the ease of localization of membrane proteins
      into shed vesicles. Taken together with the recent biophysical studies, we built
      a "fence selection model" that retrograding spectrin mesh sweeps diffusing band 3
      molecules from the tip of the membrane crenated area toward the entry of the
      crenated area, but not AChE molecules. Our study describes a novel method for
      isolation of a large number of vesicles containing special and intact membrane
      proteins from cells not by using detergents or organic solvents, but by utilizing
      the fence effect between the cytoskeleton and membrane proteins.

PMID- 10898955
TI  - Molecular mechanisms of apoptosis induced by an immunomodulating peptide on human
      monocytes.
AB  - A short immunomodulating peptide (Pa) containing a defined structural motif
      present in a number of extracellular matrix proteins and autoantigens was found
      to stimulate human monocytes. Pa-induced apoptosis of isolated monocytes, as
      indicated by internucleosomal DNA cleavage, increased annexin V binding capacity
      and cleavage of caspase substrates, such as poly(ADP)ribosylpolymerase. In
      addition, Bcl-2 protein levels were downregulated during Pa-induced cell death.
      Nuclear extracts of monocytes incubated with Pa showed higher neutral, Ca(2+)
      dependent DNase activity than those obtained from nontreated monocytes. Caspase
      inhibitors prevented Pa-induced apoptosis, Bcl-2 depletion, and DNase activation.
      Treatment of monocytes with Pa activated c-Jun N-terminal kinases and p38 kinase,
      in an acidic sphingomyelinase- and caspase-dependent fashion. Pa-induced
      apoptosis was blocked by selective inhibitors of p38 kinase (SB203580) and acidic
      sphingomyelinase (SR33557). These results indicate that JNK and p38 kinase
      stimulation as well as monocyte apoptosis induced by Pa could depend, at least in
      part, on early activation of acidic sphingomyelinase.

PMID- 10898956
TI  - Determination of the disulfide bond and its possible role in tobacco acetolactate
      synthase.

PMID- 10898957
TI  - Monopolar protrusive activity: a new morphogenic cell behavior in the neural
      plate dependent on vertical interactions with the mesoderm in Xenopus.
AB  - We compared the type and patterning of morphogenic cell behaviors driving
      convergent extension of the Xenopus neural plate in the presence and absence of
      persistent vertical signals from the mesoderm by videorecording explants of deep
      neural tissue with involuted mesoderm attached and of deep neural tissue alone.
      In deep neural-over-mesoderm explants, neural plate cells express monopolar
      medially directed motility and notoplate cells express randomly oriented
      motility, two new morphogenic cell behaviors. In contrast, in deep neural
      explants (without notoplate), all cells express bipolar mediolateral cell
      motility. Deep neural-over-mesoderm and deep neural explants also differ in
      degree of neighbor exchange during mediolateral cell intercalation. In deep
      neural-over-mesoderm explants, cells intercalate conservatively, whereas in deep
      neural explants cells intercalate more promiscuously. Last, in both deep neural
      over-mesoderm and deep neural explants, morphogenic cell behaviors differentiate
      in an anterior-to-posterior and lateral-to-medial progression. However, in deep
      neural-over-mesoderm explants, morphogenic behaviors first differentiate in
      intervals along the anteroposterior axis, whereas in deep neural explants,
      morphogenic behaviors differentiate continuously from the anterior end of the
      tissue posteriorly. These results describe new morphogenic cell behaviors driving
      neural convergent extension and also define roles for signals from the mesoderm,
      up to and beyond late gastrulation, in patterning these cell behaviors.

PMID- 10898958
TI  - Too much interference: injection of double-stranded RNA has nonspecific effects
      in the zebrafish embryo.
AB  - We have investigated the ability of double-stranded RNA (dsRNA) to inhibit gene
      expression in a vertebrate, the zebrafish, Danio rerio. Injection of dsRNA
      corresponding to the T-box gene tbx16/spadetail (spt) into early wild-type
      embryos caused a rapid and dramatic loss of tbx16/spt mRNA in the blastula. mRNAs
      from the papc, tbx6, and gata1 genes, which depend on tbx16/spt function for
      their expression, were reduced, apparently mimicking the spt mutant phenotype.
      However, mRNAs from a number of genes that are unaffected by the spt mutation,
      such as beta catenin, stat3, and no tail, were also lost, indicating that the
      "interference" effect of tbx16/spt dsRNA was not restricted to the endogenous
      tbx16/spt mRNA. We compared the effects of injecting dsRNA from the zebrafish
      tbx16/spadetail, nieuwkoid/bozozok, and Brachyury/no tail genes with dsRNA from
      the bacterial lacZ gene. In each case the embryos displayed a variable syndrome
      of abnormalities at 12 and 24 h postfertilization. In blind studies, we could not
      distinguish between the effects of the various dsRNAs. Consistent with a common
      effect of dsRNA, regardless of sequence, injection of dsRNA from the lacZ gene
      was likewise effective in strongly reducing tbx16/spt and beta catenin mRNA in
      the blastula. These findings indicate that, despite published reports, the
      current methodology of double-stranded RNA interference is not a practical
      technique for investigating zygotic gene function during early zebrafish
      development.

PMID- 10898959
TI  - Thoracic skeletal defects in myogenin- and MRF4-deficient mice correlate with
      early defects in myotome and intercostal musculature.
AB  - Myogenin and MRF4 are skeletal muscle-specific bHLH transcription factors
      critical for muscle development. In addition to a variety of skeletal muscle
      defects, embryos homozygous for mutations in myogenin or MRF4 display phenotypes
      in the thoracic skeleton, including rib fusions and sternal defects. These
      skeletal defects are likely to be secondary because myogenin and MRF4 are not
      expressed in the rib cartilage or sternum. In this study, the requirement for
      myogenin and MRF4 in thoracic skeletal development was further examined. When a
      hypomorphic allele of myogenin and an MRF4-null mutation were placed together,
      the severity of the thoracic skeletal defects was greatly increased and included
      extensive rib cartilage fusion and fused sternebrae. Additionally, new rib
      defects were observed in myogenin/MRF4 compound mutants, including a failure of
      the rib cartilage to contact the sternum. These results suggested that myogenin
      and MRF4 share overlapping functions in thoracic skeletal formation. Spatial
      expression patterns of skeletal muscle-specific markers in myogenin- and MRF4
      mutant embryos revealed early skeletal muscle defects not previously reported.
      MRF4-/- mice displayed abnormal intercostal muscle morphology, including
      bifurcation and fusion of adjacent intercostals. myogenin/MRF4-mutant
      combinations displayed ventral myotome defects, including a failure to express
      normal levels of myf5. The results suggested that the early muscle defects
      observed in myogenin and MRF4 mutants may cause subsequent thoracic skeletal
      defects, and that myogenin and MRF4 have overlapping functions in ventral myotome
      differentiation and intercostal muscle morphogenesis.

PMID- 10898960
TI  - An F-Box/WD40 repeat-containing protein important for Dictyostelium cell-type
      proportioning, slug behaviour, and culmination.
AB  - FbxA is a novel member of a family of proteins that contain an F-box and WD40
      repeats and that target specific proteins for degradation via proteasomes. In
      fruiting bodies formed from cells where the fbxA gene is disrupted (fbxA(-)
      cells), the spore mass fails to fully ascend the stalk. In addition, fbxA(-)
      slugs continue to migrate under environmental conditions where the parental
      strain immediately forms fruiting bodies. Consistent with this latter behaviour,
      the development of fbxA(-) cells is hypersensitive to ammonia, the signaling
      molecule that regulates the transition from the slug stage to terminal
      differentiation. The slug comprises an anterior prestalk region and a posterior
      prespore region and the fbxA mRNA is highly enriched in the prestalk cells. The
      prestalk zone of the slug is further subdivided into an anterior pstA region and
      a posterior pstO region. In fbxA(-) slugs the pstO region is reduced in size and
      the prespore region is proportionately expanded. Our results indicate that FbxA
      is part of a regulatory pathway that controls cell fate decisions and spatial
      patterning via regulated protein degradation.

PMID- 10898961
TI  - Metaphase I arrest and spontaneous parthenogenetic activation of strain LTXBO
      oocytes: chimeric reaggregated ovaries establish primary lesion in oocytes.
AB  - Oocytes of strain LT mice, and related strains such as LTXBO, exhibit a high
      incidence of arrest in the progression of meiosis at metaphase I (MI) and in
      spontaneous parthenogenetic activation. Activation of these oocytes within the
      ovary leads to the formation of ovarian teratomas. In this study, the role of the
      oocyte's companion granulosa cells, the cumulus cells, was investigated using
      fully grown oocytes matured in vitro after isolation from LTXBO mice. Results
      showed that the role of cumulus cells in MI arrest is dichotomous. Cumulus cells
      temporarily helped to sustain MI arrest, but they also promoted a delayed
      progression to metaphase II. Cumulus cells also promoted parthenogenetic
      activation that occurred in association with the delayed progression to metaphase
      II. Next, the question of whether the lesion(s) promoting MI arrest and
      spontaneous activation is due to defects in the somatic cells or is intrinsic to
      the oocyte was addressed using chimeric reaggregated ovaries. An improved method
      for completely exchanging the germ cell and the somatic cell compartments of
      ovaries from newborn mice is described. These chimeric reaggregated ovaries,
      grafted beneath the renal capsule of SCID mice, allowed the complete development
      of LTXBO oocytes to occur in association with somatic cells from control
      (B6SJLF(1)) ovaries and development of control oocytes in association with LTXBO
      somatic cells. Oocyte growth and follicular development appeared generally normal
      in reaggregated ovaries. High incidences of MI arrest and spontaneous activation
      of LTXBO oocytes occurred regardless of the genotype of the somatic cells.
      Moreover, there was a low incidence of MI arrest and spontaneous activation of
      control oocytes, even though they underwent complete development and maturation
      associated with LTXBO somatic cells. It is concluded that the phenotypes of MI
      arrest and parthenogenetic activation in LTXBO oocytes are defects caused by
      lesions intrinsic to the oocyte. Nevertheless, the oocyte's companion somatic
      cells play crucial roles in the expression of these lesions.

PMID- 10898962
TI  - Characterization of Brachyury-downstream notochord genes in the Ciona
      intestinalis embryo.
AB  - The notochord has two major roles during chordate embryogenesis, as a source of
      inductive signals for the patterning of neural tube and paraxial mesoderm and as
      a supportive organ of the larval tail. Despite the recent identification of
      mutations that affect the notochord development in vertebrate embryos, little is
      known about genes that are expressed in the differentiating notochord itself. In
      the urochordate ascidian Ciona intestinalis, Brachyury (Ci-Bra) plays a key role
      in notochord differentiation. In a previous study, we isolated cDNA clones for
      nearly 40 potential Ci-Bra target genes that are expressed in notochord cells (H.
      Takahashi et al., 1999, Genes Dev. 13, 1519-1523). Here we characterized 20 of
      them by determining the complete nucleotide sequences of the cDNAs. These genes
      encode a broad spectrum of divergent proteins associated with notochord formation
      and function. Two genes encode ascidian homologs of the Drosophila Prickle LIM
      domain proteins and another encodes the ERM protein, all 3 of which appear to be
      involved in the control of cytoskeletal architecture. In addition, genes for
      netrin, leprecan, cdc45, ATP:citrate lyase, ATP sulfurylase/APS kinase, protein
      tyrosine phosphatase, beta4-galactosyltransferase, fibrinogen-like protein,
      divergent tropomyosin-like proteins, and Drosophila Pellino-like protein were
      identified. The observation of the netrin gene expression in the notochord may
      provide the first molecular evidence that the ascidian notochord is a source of
      signals as in vertebrates. In addition, the present information should be used to
      identify nonchordate deuterostome tissues homologous to the notochord as well as
      genes which are expressed in the notochord cells of vertebrate embryos.

PMID- 10898963
TI  - Spatial and temporal expression of a Polysphondylium spore-specific gene.
AB  - In the cellular slime mold Polysphondylium spherical masses of cells are
      periodically released from the base of the culminating sorogen. These whorls
      undergo a morphogenetic transformation from spherical to radial symmetry, marked
      by the early emergence of a radially symmetric prepattern on the whorl surface.
      In previous experiments, morphogenesis was followed by observing prestalk cell
      markers. Here we describe the isolation and characterization of a spore coat gene
      whose expression pattern is the negative image of the prestalk pattern. To study
      the molecular mechanism of sp-45 gene regulation, we have cloned and analyzed the
      sp-45 promoter. Deletion analysis localized a single positive regulatory element
      (PRE) to a 106-bp fragment between positions -246 and -352 of the upstream coding
      sequence. This fragment can be further divided into a promoter-proximal and
      promoter-distal PRE and a 29-bp sequence between them. The distal PRE can
      regulate prespore expression when fused to a nonfunctioning basal promoter. The
      distal PRE contains two adjacent essential elements, a Gr box (GTGATATAGTGG) and
      a TA box (TAATATATT). Each element can drive prespore cell-specific reporter gene
      expression independently when incorporated into a nonfunctional promoter. Our
      results also show that prespore cell-specific gene expression is solely under
      positive regulation, with no evidence for spore-specific enhancers or cis-acting
      negative regulatory elements. By fusing GFP to the C-terminus of sp-45, we have
      demonstrated that the graded gene expression of SP45 in the sorogen is regulated
      by a sequence lying within the sp-45 coding sequence. The temporal and spatial
      expression pattern of this protein, taken together with the prestalk expression
      pattern, demonstrates unambiguously that the radial symmetries that emerge in the
      whorl are established by a system of positional coordinates and that cell sorting
      plays little if any role in this process.

PMID- 10898965
TI  - James W. Lash (October 24, 1929-January 11, 2000).

PMID- 10898964
TI  - Conserved molecular mechanism for the stage specificity of the mosquito
      vitellogenic response to ecdysone.
AB  - In the mosquito Aedes aegypti, the adult female becomes competent for a
      vitellogenic response to ecdysone after previtellogenic development. Here, we
      show that betaFTZ-F1, the nuclear receptor implicated as a competence factor for
      stage-specific responses to ecdysone during Drosophila metamorphosis, serves a
      similar function during mosquito vitellogenesis. AaFTZ-F1 is expressed highly in
      the mosquito fat body during pre- and postvitellogenic periods when ecdysteroid
      titers are low. The mosquito AaFTZ-F1 transcript nearly disappears in mid
      vitellogenesis when ecdysteroid titers are high. An expression peak of HR3, a
      nuclear receptor implicated in the activation of betaFTZ-F1 in Drosophila,
      precedes each rise in mosquito FTZ-F1 expression. In in vitro fat body culture,
      AaFTZ-F1 expression is inhibited by 20-hydroxyecdysone (20E) and superactivated
      by its withdrawal. Following in vitro AaFTZ-F1 superactivation, a secondary 20E
      challenge results in superinduction of the early AaE75 gene and the late target
      VCP gene. Electrophoretic mobility-shift assays show that the onset of ecdysone
      response competence in the mosquito fat body is correlated with the appearance of
      the functional AaFTZ-F1 protein at the end of the previtellogenic development.
      These findings suggest that a conserved molecular mechanism for controlling stage
      specificity is reiteratively used during metamorphic and reproductive responses
      to ecdysone.

PMID- 10898966
TI  - Commitment factors for T helper cells.
AB  - Cytokines are dominant factors in driving the development of T helper cell
      subsets via specific signaling pathways. Transcription factors specific to the T
      helper cell lineages have also been shown to determine the commitment of Th1 and
      Th2 cells to the production of distinct profiles of cytokines.

PMID- 10898967
TI  - The controlled chaos of shifty pathogens.
AB  - Bacterial pathogens use novel mechanisms to vary their surface structures. Three
      new genome sequences provide a perspective on these mechanisms in Borrelia
      burgdorferi, Neisseria meningitidis, and Campylobacter jejuni, which cause lyme
      disease, meningitis and gastroenteritis, respectively.

PMID- 10898968
TI  - Motor cortex rules for learning and memory.
AB  - Primary motor cortex has a complex, interconnected anatomical and functional
      architecture with dynamic properties. Recent evidence suggests that,
      concomitantly with regulating muscle activity and movements, the motor cortex
      makes key contributions to learning and remembering motor skills.

PMID- 10898969
TI  - Rac and roll over the corpses.
AB  - A genetic pathway controlling the removal of apoptotic corpses has now been
      identified in the nematode. Mammalian homologs of the components of this pathway
      are already known to have key roles in cell motility and integrin-mediated
      signaling, suggesting that the three processes are mechanistically related.

PMID- 10898970
TI  - Spillover in the spotlight.
AB  - Fast neurotransmission in the brain is typically mediated by local actions of
      transmitters at ionotropic receptors within synaptic contacts. Recent studies now
      reveal that, in addition to point-to-point signaling, amino-acid transmitters
      mediate diffuse signaling at extrasynaptic metabotropic receptors.

PMID- 10898971
TI  - Sm-like proteins wRING the neck of mRNA.
AB  - Ring-shaped structures containing seven Sm or Sm-like proteins are stable
      components of several small nuclear ribonucleoprotein particles that function in
      pre-mRNA splicing. Recent reports describe a role for a distinct complex of seven
      Sm-like proteins in a very different process: mRNA degradation.

PMID- 10898972
TI  - The salty tale of Arabidopsis.
AB  - High concentrations of sodium chloride are toxic to most plant species. New
      insights into the mechanisms by which plants tolerate salt have emerged from the
      identification of genes in Arabidopsis thaliana that play a critical part in
      physiological resistance to salt.

PMID- 10898973
TI  - An alternative view of perceptual rivalry.
AB  - The mechanism by which one or the other view of an ambiguous figure - such as the
      Necker cube - gains dominance has been unclear. Recent evidence suggests that the
      right frontoparietal cortex is responsible for the selection process, and that
      each cortical hemisphere represents one of the two rivalling percepts.

PMID- 10898974
TI  - The trouble with tribbles.
AB  - Cell division and cell movements must be coordinated during development. A novel
      inhibitor of cell division, Tribbles, has been identified that blocks mitosis at
      a critical point in Drosophila morphogenesis. The data support a role for
      Tribbles in promoting proteolytic degradation of String/Cdc25, a key regulator of
      mitosis.

PMID- 10898975
TI  - Dynamics of interphase microtubules in Schizosaccharomyces pombe.
AB  - BACKGROUND: Microtubules in interphase Schizosaccharomyces pombe are essential
      for maintaining the linear growth habit of these cells. The dynamics of assembly
      and disassembly of these microtubules are so far uncharacterised. RESULTS: Live
      cell confocal imaging of alpha1 tubulin tagged with enhanced green fluorescent
      protein revealed longitudinally oriented, dynamically unstable interphase
      microtubule assemblies (IMAs). The IMAs were uniformly bright along their length
      apart from a zone of approximately doubly intense fluorescence commonly present
      close to their centres. The ends of each IMA switched from growth ( approximately
      3.0 microm/min) to shrinkage ( approximately 4.5 microm/min) at 1.0 events per
      minute and from shrinkage to growth at 1.9 events per minute, and the two ends
      were equivalently dynamic, suggesting equivalent structure. We accordingly
      propose a symmetrical model for microtubule packing within the IMAs, in which
      microtubules are plus ends out and overlap close to the equator of the cell. IMAs
      may contain multiple copies of this motif; if so, then within each IMA end, the
      microtubule ends must synchronise catastrophe and rescue. When both ends of an
      IMA lodge in the hemispherical cell ends, the IMAs start to bend under
      compression and their overall growth rate is inhibited about twofold. Similar
      microtubule dynamics were observed in cells ranging in size from half to twice
      normal length. Patterned photobleaching indicated no detectable treadmilling or
      microtubule sliding during interphase. CONCLUSIONS: The consequence of the
      mechanisms described is continuous recruitment of microtubule ends to the ends of
      growing cells, supporting microtubule-based transport into the cell ends and
      qualitatively accounting for the essential role for microtubules in directing
      linear cell growth in S. pombe.

PMID- 10898976
TI  - The hypersensitive response facilitates plant infection by the necrotrophic
      pathogen Botrytis cinerea.
AB  - BACKGROUND: Plants have evolved efficient mechanisms to combat pathogen attack.
      One of the earliest responses to attempted pathogen attack is the generation of
      oxidative burst that can trigger hypersensitive cell death. This is called the
      hypersensitive response (HR) and is considered to be a major element of plant
      disease resistance. The HR is thought to deprive the pathogens of a supply of
      food and confine them to initial infection site. Necrotrophic pathogens, such as
      the fungi Botrytis cinerea and Sclerotinia sclerotiorum, however, can utilize
      dead tissue. RESULTS: Inoculation of B. cinerea induced an oxidative burst and
      hypersensitive cell death in Arabidopsis. The degree of B. cinerea and S.
      sclerotiorum pathogenicity was directly dependent on the level of generation and
      accumulation of superoxide or hydrogen peroxide. Plant cells exhibited markers of
      HR death, such as nuclear condensation and induction of the HR-specific gene
      HSR203J. Growth of B. cinerea was suppressed in the HR-deficient mutant dnd1, and
      enhanced by HR caused by simultaneous infection with an avirulent strain of the
      bacterium Pseudomonas syringae. HR had an opposite (inhibitory) effect on a
      virulent (biotrophic) strain of P. syringae. Moreover, H(2)O(2) levels during HR
      correlated positively with B. cinerea growth but negatively with growth of
      virulent P. syringae. CONCLUSIONS: We show that, although hypersensitive cell
      death is efficient against biotrophic pathogens, it does not protect plants
      against infection by the necrotrophic pathogens B. cinerea and S. sclerotiorum.
      By contrast, B. cinerea triggers HR, which facilitates its colonization of
      plants. Hence, these fungi can exploit a host defense mechanism for their
      pathogenicity.

PMID- 10898977
TI  - Cdc42 is required for PIP(2)-induced actin polymerization and early development
      but not for cell viability.
AB  - BACKGROUND: Cdc42 and other Rho GTPases are conserved from yeast to humans and
      are thought to regulate multiple cellular functions by inducing coordinated
      changes in actin reorganization and by activating signaling pathways leading to
      specific gene expression. Direct evidence implicating upstream signals and
      components that regulate Cdc42 activity or for required roles of Cdc42 in
      activation of downstream protein kinase signaling cascades is minimal, however.
      Also, whereas genetic analyses have shown that Cdc42 is essential for cell
      viability in yeast, its potential roles in the growth and development of
      mammalian cells have not been directly assessed. RESULTS: To elucidate potential
      functions of Cdc42 mammalian cells, we used gene-targeted mutation to inactivate
      Cdc42 in mouse embryonic stem (ES) cells and in the mouse germline. Surprisingly,
      Cdc42-deficient ES cells exhibited normal proliferation and phosphorylation of
      mitogen- and stress-activated protein kinases. Yet Cdc42 deficiency caused very
      early embryonic lethality in mice and led to aberrant actin cytoskeletal
      organization in ES cells. Moreover, extracts from Cdc42-deficient cells failed to
      support phosphatidylinositol 4,5-bisphosphate (PIP(2))-induced actin
      polymerization. CONCLUSIONS: Our studies clearly demonstrate that Cdc42 mediates
      PIP(2)-induced actin assembly, and document a critical and unique role for Cdc42
      in this process. Moreover, we conclude that, unexpectedly, Cdc42 is not necessary
      for viability or proliferation of mammalian early embryonic cells. Cdc42 is,
      however, absolutely required for early mammalian development.

PMID- 10898978
TI  - Identification of a phragmoplast-associated kinesin-related protein in higher
      plants.
AB  - The phragmoplast executes cytokinesis in higher plants. The major components of
      the phragmoplast are microtubules, which are arranged in two mirror-image arrays
      perpendicular to the division plane [1]. The plus ends of these microtubules are
      located near the site of the future cell plate. Golgi-derived vesicles are
      transported along microtubules towards the plus ends to deliver materials bound
      for the cell plate [2] [3]. During cell division, rapid microtubule
      reorganization in the phragmoplast requires the orchestrated activities of
      microtubule motor proteins such as kinesins. We isolated an Arabidopsis cDNA
      clone of a gene encoding an amino-terminal motor kinesin, AtPAKRP1, and have
      determined the partial sequence of its rice homolog. Immunofluorescence
      experiments with two sets of specific antibodies revealed consistent localization
      of AtPAKRP1 and its homolog in Arabidopsis and rice cells undergoing anaphase,
      telophase and cytokinesis. AtPAKRP1 started to accumulate along microtubules
      towards the spindle midzone during late anaphase. Once the phragmoplast
      microtubule array was established, AtPAKRP1 conspicuously localized to
      microtubules near the future cell plate. Our results provide evidence that
      AtPAKRP1 is a hitherto unknown motor that may take part in the establishment
      and/or maintenance of the phragmoplast microtubule array.

PMID- 10898979
TI  - Adhesion to target cells is disrupted by the killer cell inhibitory receptor.
AB  - Killer cell immunoglobulin-like receptors (KIR) inhibit the cytotoxic activity of
      natural killer (NK) cells by recruitment of the tyrosine phosphatase SHP-1 to
      immunoreceptor tyrosine-based inhibition motif (ITIM) sequences in the KIR
      cytoplasmic tail [1]. The precise steps in the NK activation pathway that are
      inhibited by KIR are yet to be defined. Here, we have studied whether the initial
      step of adhesion molecule LFA-1-dependent adhesion to target cells was altered by
      the inhibitory signal. Using stable expression of an HLA-C-specific KIR in the NK
      cell line YTS [2] and a two-color flow cytometry assay for conjugate formation,
      we show that adhesion to a target cell expressing cognate HLA-C was disrupted by
      KIR engagement. Conjugate formation was abruptly interrupted by KIR within less
      than 5 minutes. Inhibition of adhesion to target cells was mediated by a chimeric
      KIR molecule carrying catalytically active SHP-1 in place of its cytoplasmic
      tail. These results suggest that other ITIM-bearing receptors, many of which have
      no known function, may regulate adhesion in a wide variety of cell types.

PMID- 10898980
TI  - Interaction of the TNF homologues BLyS and APRIL with the TNF receptor homologues
      BCMA and TACI.
AB  - BLyS (also called TALL-1, THANK, or BAFF) [1] [2] [3] [4] is a member of the
      tumor necrosis factor (TNF) gene family that stimulates proliferation and
      immunoglobulin production by B cells. BLyS interacts with the TNF receptor (TNFR)
      homologue TACI (transmembrane activator and CAML-interactor) [5], and treatment
      of mice with a TACI-Fc fusion protein abolishes germinal center formation after
      antigenic challenge [6]. Here we report a novel interaction between BLyS and
      another TNFR homologue, BCMA (B cell maturation antigen) [7] [8]. Further, the
      TNF homologue APRIL [9], a close relative of BLyS, also bound to BCMA and TACI.
      BLyS or APRIL activated nuclear factor-kappaB (NF-kappaB) through TACI and BCMA,
      and each ligand stimulated immunoglobulin M (IgM) production by peripheral blood
      B cells. These results define a dual ligand-receptor system that may play an
      important role in humoral immunity.

PMID- 10898981
TI  - Rapid induction of apoptosis mediated by peptides that bind initiation factor
      eIF4E.
AB  - Overexpression of the translation initiation factor eIF4E leads to cell
      transformation and occurs in a number of human cancers [1]. mRNA translation and
      cell growth can be regulated through the availability of eIF4E to form initiation
      complexes by binding to eIF4G. The availability of eIF4E is blocked through the
      binding of members of a family of eIF4E-binding proteins (4E-BPs) [2] [3].
      Indeed, cell transformation caused by the overexpression of eIF4E can be reversed
      by the overexpression of 4E-BPs [4] [5] [6] [7] [8]. To study the role of eIF4E
      in cell transformation, we developed a series of peptides based on the conserved
      eIF4E-binding motifs in 4E-BPs and eIF4G [9] linked to the penetratin peptide
      carrier sequence, which mediates the rapid transport of peptides across cell
      membranes. Surprisingly, introduction of these eIF4E-binding peptides into MRC5
      cells led to rapid, dose-dependent cell death, with characteristics of apoptosis.
      Single alanine substitutions at key positions in the peptides impair their
      binding to eIF4E and markedly reduce their ability to induce apoptosis. A triple
      alanine substitution, which abolishes binding to eIF4E, renders the peptide
      unable to induce apoptosis. Our data provide strong evidence that the peptides
      induce apoptosis through binding to eIF4E. They do not induce apoptosis through
      inhibition of protein synthesis, as chemical inhibitors of translation did not
      induce apoptosis or affect peptide-induced cell death. Thus these new data
      indicate that eIF4E has a direct role in controlling cell survival that is not
      linked to its known role in mRNA translation.

PMID- 10898982
TI  - Allele-specific expression patterns of interleukin-2 and Pax-5 revealed by a
      sensitive single-cell RT-PCR analysis.
AB  - Autosomal genes that are subject to random allelic inactivation (RAI), like
      imprinted genes [1] and genes subject to X-inactivation [2], require mechanisms
      that dictate the differential transcriptional regulation of two sequence
      identical alleles. RAI genes include olfactory receptor genes [3], and the
      various genes encoding antigen receptors on lymphocytes (immunoglobulin genes, T
      cell receptor genes and NK receptor genes [4] [5] [6] [7]). These observations
      raise the possibility that other genes might be similarly regulated. Moreover, an
      interesting possibility is that certain genes might be monoallelically expressed
      in some cells and biallelically expressed in others. Recently, reports of
      monoallelic expression of interleukin-2 (IL-2) [8] [9] and IL-4 [10] [11] have
      raised the possibility that the cytokine gene family may be subject to
      monoallelic expression. Another report suggests that the gene encoding the
      transcription factor Pax-5, which is involved in B-cell (and cerebellar)
      development [12] [13], is also subject to monoallelic expression [14]. Using a
      novel single-cell reverse transcription-polymerase chain reaction (RT-PCR)
      approach, we have analyzed the IL-2 and Pax-5 genes in mice. We found that IL-2
      is monoallelically transcribed in some T cells and biallelically transcribed in
      others, raising interesting questions regarding cytokine gene regulation.
      Additionally, our analyses suggest that Pax-5 is consistently biallelically
      transcribed. Thus, the IL-2 gene and other cytokine genes may be regulated in a
      stochastic manner that results in 0, 1 or 2 alleles of a given cytokine gene
      expressed in each T cell. This type of regulation could account for the wide
      variety of different combinations of cytokine genes expressed in individual T
      cells and therefore plays a role in the generation of T cells with a range of
      different effector functions.

PMID- 10898983
TI  - Interactions between the cellular and humoral immune responses in Drosophila.
AB  - Drosophila has highly efficient defenses against infection. These include both
      cellular immune responses, such as the phagocytosis of invading microorganisms,
      and humoral immune responses, such as the secretion of antimicrobial peptides
      into the hemolymph [1] [2]. These defense systems are thought to interact, but
      the nature and extent of these interactions is not known. Here we describe a
      method for inhibiting phagocytosis in Drosophila blood cells (hemocytes) by
      injecting polystyrene beads into the body cavity. This treatment does not in
      itself make a fly susceptible to Escherichia coli infection. However, when
      performed on flies carrying the mutation immune deficiency (imd), which affects
      the humoral immune response [3], the treatment results in a striking decrease in
      resistance to infection. We therefore carried out a sensitized genetic screen to
      identify immunocompromised mutants by co-injecting beads and E. coli. From this
      screen, we identified a new gene we have named red shirt and identified the
      caspase Dredd as a regulator of the Drosophila immune response. The observation
      that mutants with defects in the humoral immune response are further
      immunocompromised by blocking phagocytosis, and thus inhibiting the cellular
      immune response, shows that the Drosophila cellular and humoral immune responses
      act in concert to fight infection.

PMID- 10898984
TI  - Evidence from multiple gene sequences indicates that termites evolved from wood
      feeding cockroaches.
AB  - Despite more than half a century of research, the evolutionary origin of termites
      remains unresolved [1] [2] [3]. A clear picture of termite ancestry is crucial
      for understanding how these insects evolved eusociality, particularly because
      they lack the haplodiploid genetic system associated with eusocial evolution in
      bees, ants, wasps and thrips [4] [5]. Termites, together with cockroaches and
      praying mantids, constitute the order Dictyoptera, which has been the focus of
      numerous conflicting phylogenetic studies in recent decades [6] [7] [8] [9] [10]
      [11] [12]. With the aim of settling the debate over the sister-group of termites,
      we have determined the sequences of genes encoding 18S ribosomal RNA,
      mitochondrial cytochrome oxidase subunit II (COII) and endogenous endo-beta-1, 4
      glucanase (EG) from a diverse range of dictyopterans. Maximum parsimony and
      likelihood analyses of these sequences revealed strong support for a clade
      consisting of termites and subsocial, wood-feeding cockroaches of the genus
      Cryptocercus. This clade is nested within a larger cockroach clade, implicating
      wood-feeding cockroaches as an evolutionary intermediate between primitive non
      social taxa and eusocial termites.

PMID- 10898985
TI  - Sensory and cognitive contributions of color to the recognition of natural
      scenes.
AB  - Although color plays a prominent part in our subjective experience of the visual
      world, the evolutionary advantage of color vision is still unclear [1] [2], with
      most current answers pointing towards specialized uses, for example to detect
      ripe fruit amongst foliage [3] [4] [5] [6]. We investigated whether color has a
      more general role in visual recognition by looking at the contribution of color
      to the encoding and retrieval processes involved in pattern recognition [7] [8]
      [9]. Recognition accuracy was higher for color images of natural scenes than for
      luminance-matched black and white images, and color information contributed to
      both components of the recognition process. Initially, color leads to an image
      coding advantage at the very early stages of sensory processing, most probably by
      easing the image-segmentation task. Later, color leads to an advantage in
      retrieval, presumably as the result of an enhanced image representation in memory
      due to the additional attribute. Our results ascribe color vision a general role
      in the processing of visual form, starting at the very earliest stages of
      analysis: color helps us to recognize things faster and to remember them better.

PMID- 10898986
TI  - The Est3 protein is a subunit of yeast telomerase.
AB  - EST1, EST2, EST3 and TLC1 function in a single pathway for telomere replication
      in the yeast Saccharomyces cerevisiae [1] [2], as would be expected if these
      genes all encode components of the same complex. Est2p, the reverse transcriptase
      protein subunit, and TLC1, the templating RNA, are subunits of the catalytic core
      of yeast telomerase [3] [4] [5]. In contrast, mutations in EST1, EST3 or CDC13
      eliminate telomere replication in vivo [1] [6] [7] [8] but are dispensable for in
      vitro telomerase catalytic activity [2] [9]. Est1p and Cdc13p, as components of
      telomerase and telomeric chromatin, respectively, cooperate to recruit telomerase
      to the end of the chromosome [7] [10]. However, Est3p has not yet been
      biochemically characterized and thus its specific role in telomere replication is
      unclear. We show here that Est3p is a stable component of the telomerase
      holoenzyme and furthermore, association of Est3p with the enzyme requires an
      intact catalytic core. As predicted for a telomerase subunit, fusion of Est3p to
      the high affinity Cdc13p telomeric DNA binding domain greatly increases access of
      telomerase to the telomere. Est1p is also tightly associated with telomerase;
      however, Est1p is capable of forming a stable TLC1-containing complex even in the
      absence of Est2p or Est3p. Yeast telomerase therefore contains a minimum of three
      Est proteins for which there is both in vivo and in vitro evidence for their role
      in telomere replication as subunits of the telomerase complex.

PMID- 10898987
TI  - A ubiquitous family of putative gap junction molecules.

PMID- 10898988
TI  - A floral boost.

PMID- 10898989
TI  - Mastermind is a putative activator for Notch.

PMID- 10898990
TI  - All about Arabidopsis.

PMID- 10898991
TI  - EXXcellence in science.

PMID- 10898992
TI  - Cerebellar function: coordination, learning or timing?
AB  - Theories of cerebellar function have largely involved three ideas: movement
      coordination, motor learning or timing. New evidence indicates these distinctions
      are not particularly meaningful, as the cerebellum influences movement execution
      by feedforward use of sensory information via temporally specific learning.

PMID- 10898993
TI  - DNA topology: feeling the pulse of a topoisomerase.
AB  - The action of individual type II DNA topoisomerases has been followed in real
      time by observing the elastic response of single DNA molecules to sequential
      strand passage events. Micromanipulation methods provide a complementary approach
      to biochemical studies for investigating the mechanism of DNA topoisomerases.

PMID- 10898994
TI  - Endocytosis: why not wait to deubiquitinate?
AB  - Deubiquitination by the Fat facets protein - a regulator of photoreceptor
      differentiation during Drosophila eye development - has been found to activate
      endocytosis, while ubiquitination inhibits endocytosis. Surprisingly, this is the
      opposite effect that ubiquitination has on endocytosis of many plasma membrane
      proteins.

PMID- 10898995
TI  - Language and thought: does grammar makes us smart?
AB  - Many philosophers and psychologists believe that only people with rich language
      skills are capable of abstract reasoning. A man with a severe linguistic
      impairment poses a striking challenge to this view.

PMID- 10898996
TI  - ER stress response: getting the UPR hand on misfolded proteins.
AB  - Unfolded proteins are constantly delivered to the ER lumen, where they must be
      removed by folding or degradation. Recent studies show that the 'unfolded protein
      response' controls essentially all aspects of ER function, coordinating these two
      fates for misfolded proteins in a process necessary for normal cell life.

PMID- 10898997
TI  - Genomic sequencing: the complexity conundrum.
AB  - The concept of 'organismal complexity' has had a chequered career in genetics,
      with no rigorous operational definition available for the term. The recent
      finding that Drosophila melanogaster has more than four thousand fewer genes than
      the nematode forces a re-examination of whether gene number, in itself, can be
      taken as any real guide to complexity.

PMID- 10898998
TI  - Adhesion signaling: PAK meets Rac on solid ground.
AB  - Interaction of cells with the extracellular matrix influences various aspects of
      cellular behavior. A recent study shows that cell-substrate adhesion is necessary
      for effective coupling of the small GTPase Rac to its effector PAK.

PMID- 10898999
TI  - Clock proteins: turned over after hours?
AB  - Light sensitivity and the involvement of unstable proteins are key features of
      circadian clocks. Both photoreception and ubiquitin conjugation may be associated
      with nuclear regulators encoded by genes recently identified in Arabidopsis.

PMID- 10899000
TI  - Signaling pathways and cell mechanics involved in wound closure by epithelial
      cell sheets.
AB  - BACKGROUND: Sheets of cells move together as a unit during wound healing and
      embryonic tissue movements, such as those occurring during gastrulation and
      neurulation. We have used epithelial wound closure as a model system for such
      movements and examined the mechanisms of closure and the importance of the Rho
      family of Ras-related small GTPases in this process. RESULTS: Wounds induced in
      Madin-Darby canine kidney (MDCK) epithelial cell monolayers close by Rac- and
      phosphoinositide-dependent cell crawling, with formation of lamellipodia at the
      wound margin, and not by contraction of a perimarginal actomyosin purse-string.
      Although Rho-dependent actin bundles usually form at the margin, neither Rho
      activity nor formation of these structures is required for wound closure to occur
      at a normal rate. Cdc42 activity is also not required for closure. Inhibition of
      Rho or Cdc42 results, however, in statistically significant decreases in the
      regularity of wound closure, as determined by the ratio of wound margin perimeter
      over the remaining denuded area at different times. The Rac-dependent force
      generation for closure is distributed over several rows of cells from the wound
      margin, as inhibition of motility in the first row of cells alone does not
      inhibit closure and can be compensated for by generation of motile force in cells
      behind the margin. Furthermore, we observed high levels of Rac-dependent actin
      assembly in the first few rows of cells from the wound margin. CONCLUSIONS:
      Wounds in MDCK cell sheets do not close by purse-string contraction but by a
      crawling behavior involving Rac, phosphoinositides and active movement of
      multiple rows of cells. This finding suggests a new distributed mode of signaling
      and movement that, nevertheless, resembles individual cell motility. Although Rho
      and Cdc42 activities are not required for closure, they have a role in
      determining the regularity of closure.

PMID- 10899001
TI  - The protocadherin PAPC establishes segmental boundaries during somitogenesis in
      xenopus embryos.
AB  - BACKGROUND: One prominent example of segmentation in vertebrate embryos is the
      subdivision of the paraxial mesoderm into repeating, metameric structures called
      somites. During this process, cells in the presomitic mesoderm (PSM) are first
      patterned into segments leading secondarily to differences required for somite
      morphogenesis such as the formation of segmental boundaries. Recent studies have
      shown that a segmental pattern is generated in the PSM of Xenopus embryos by
      genes encoding a Mesp-like bHLH protein called Thylacine 1 and components of the
      Notch signaling pathway. These genes establish a repeating pattern of gene
      expression that subdivides cells in the PSM into anterior and posterior half
      segments, but how this pattern of gene expression leads to segmental boundaries
      is unknown. Recently, a member of the protocadherin family of cell adhesion
      molecules, called PAPC, has been shown to be expressed in the PSM of Xenopus
      embryos in a half segment pattern, suggesting that it could play a role in
      restricting cell mixing at the anterior segmental boundary. RESULTS: Here, we
      examine the expression and function of PAPC during segmentation of the paraxial
      mesoderm in Xenopus embryos. We show that Thylacine 1 and the Notch pathway
      establish segment identity one segment prior to the segmental expression of PAPC.
      Altering segmental identity in embryos by perturbing the activity of Thylacine 1
      and the Notch pathway, or by treatment with a protein synthesis inhibitor,
      cycloheximide, leads to the predicted changes in the segmental expression of
      PAPC. By disrupting PAPC function in embryos using a putative dominant-negative
      or an activated form of PAPC, we show that segmental PAPC activity is required
      for proper somite formation as well as for maintaining segmental gene expression
      within the PSM. CONCLUSIONS: Segmental expression of PAPC is established in the
      PSM as a downstream consequence of segmental patterning by Thylacine 1 and the
      Notch pathway. We propose that PAPC is part of the mechanism that establishes the
      segmental boundaries between posterior and anterior cells in adjacent segments.

PMID- 10899002
TI  - Rac is required for constitutive macropinocytosis by dendritic cells but does not
      control its downregulation.
AB  - BACKGROUND: Dendritic cells use constitutive macropinocytosis to capture
      exogenous antigens for presentation on MHC molecules. Upon exposure to
      inflammatory stimuli or bacterial products such as lipopolysaccharide (LPS),
      macropinocytosis is dramatically downregulated as part of a developmental
      programme leading to dendritic cell maturation, migration and activation of T
      cells. It is not known, however, how macropinocytosis is sustained in dendritic
      cells in the absence of exogenous stimuli, nor how it is downregulated upon
      maturation. We have tested the possibility that one or more members of the Rho
      family of GTPases are involved in and control pinocytosis in dendritic cells.
      RESULTS: We established dendritic cell populations that show constitutive
      macropinocytosis that was downregulated by LPS treatment. Microinjection of
      immature cells with dominant-negative Rac (N17Rac1) or treatment with Clostridium
      difficile toxin B, the phosphoinositide 3-kinase (PI3-K) inhibitor wortmannin, or
      LPS all inhibited the formation of macropinosomes but, surprisingly, did not
      eliminate membrane ruffling. Microinjection of N17Cdc42 or the Rho inhibitor C3
      transferase eliminated actin plaques/podosomes and actin cables, respectively,
      but had little effect on the formation of macropinosomes. Surprisingly, dendritic
      cells matured with LPS had equivalent or even somewhat higher levels of active
      Rac than immature cells. Moreover, microinjection of a constitutively active form
      of Rac (V12Rac1) into mature dendritic cells did not reactivate macropinocytosis.
      CONCLUSIONS: Rac has an important role in the constitutive formation of
      macropinosomes in dendritic cells but may be required downstream of membrane
      ruffling. Furthermore, regulation of Rac activity does not appear to be the
      control point in the physiological downregulation of dendritic cell pinocytosis.
      Instead, one or more downstream effectors may be modulated to allow Rac to
      continue to regulate other cellular functions.

PMID- 10899003
TI  - The notch signalling regulator fringe acts in the Golgi apparatus and requires
      the glycosyltransferase signature motif DXD.
AB  - BACKGROUND: Signalling via the Notch receptor is a key regulator of many
      developmental processes. The differential responsiveness of Notch-expressing
      cells to the ligands Delta and Serrate is controlled by Fringe, itself essential
      for normal patterning in Drosophila and vertebrates. The mechanism of Fringe
      action, however, is not known. The protein has an amino-terminal hydrophobic
      stretch resembling a cleaved signal peptide, which has led to the widespread
      assumption that it is a secreted signalling molecule. It also has distant
      homology to bacterial glycosyltransferases, although it is not clear if this
      reflects a shared enzymatic activity, or merely a related structure. RESULTS: We
      report that a functional epitope-tagged form of Drosophila Fringe was localised
      in the Golgi apparatus. When the putative signal peptide was replaced by a
      confirmed one, Fringe no longer accumulated in the Golgi, but was instead
      efficiently secreted. This change in localisation dramatically reduced its
      biological activity, implying that the wild-type protein normally acts inside the
      cell. We show that Fringe specifically binds the nucleoside diphosphate UDP, a
      feature of many glycosyltransferases. Furthermore, specific mutation of a DxD
      motif (in the single-letter amino acid code where x is any amino acid), a
      hallmark of most glycosyltransferases that use nucleoside diphosphate sugars, did
      not affect the Golgi localisation of the protein but completely eliminated in
      vivo activity. CONCLUSIONS: These results indicate that Fringe does not exert its
      effects outside of the cell, but rather acts in the Golgi apparatus, apparently
      as a glycosyltransferase. They suggest that alteration in receptor glycosylation
      can regulate the relative efficiency of different ligands.

PMID- 10899004
TI  - The 5' upstream region of mPer1 gene contains two promoters and is responsible
      for circadian oscillation.
AB  - The mPer1 gene is assumed to be a key molecule in the regulation and functioning
      of the mammalian circadian clock, which is based on the oscillation generated by
      a transcription-(post)translation feedback loop of a set of clock genes [1].
      Robust circadian oscillation and acute light-elicited induction of mPer1 mRNA
      expression have been observed in the suprachiasmatic nucleus (SCN), the mammalian
      circadian center [2] [3]. To investigate the mechanism underlying the complex
      regulation of mPer1 expression, we isolated and characterized the 5' upstream
      region of the mPer1 gene. Unexpectedly, we identified two promoters, each
      followed by alternative first exons of mPer1. Consistent with the presence of
      multiple E-boxes in the promoters, exon-specific in situ hybridization of the SCN
      established that both promoters function in circadian oscillation and in light
      induction of mPer1 expression. Transgenic mice carrying the 5' upstream region of
      the mPer1 gene fused to the luciferase gene demonstrated that a DNA fragment
      carrying both promoter regions is sufficient to elicit striking circadian
      oscillation in the SCN and responsiveness to light. Moreover, luminescence in the
      SCN accurately mirrored the mPer1 transcriptional activity. These transgenic mice
      will be very useful for monitoring clock-specific mPer1 expression in intact
      organisms and to follow the circadian clock in real time.

PMID- 10899005
TI  - Inducible gene expression in transgenic Xenopus embryos.
AB  - The amphibian Xenopus laevis has been successfully used for many years as a model
      system for studying vertebrate development. Because of technical limitations,
      however, molecular investigations have mainly concentrated on early stages. We
      have developed a straightforward method for stage-specific induction of gene
      expression in transgenic Xenopus embryos [1] [2]. This method is based on the
      Xenopus heat shock protein 70 (Xhsp70 [3]) promoter driving the expression of
      desired gene products. We found that ubiquitous expression of the transgene is
      induced upon relatively mild heat treatment. Green fluorescent protein (GFP) was
      used as a marker to monitor successful induction of gene expression in transgenic
      embryos. We used this method to study the stage specificity of Wnt signalling
      function. Transient ectopic Wnt-8 expression during early neurulation was
      sufficient to repress anterior head development and this capacity was restricted
      to early stages of neurulation. By transient over-expression at different stages
      of development, we show that frizzled-7 disrupted morphogenesis sequentially from
      anterior to posterior along the dorsal axis as development proceeds. These
      results demonstrate that this method for inducible gene expression in transgenic
      Xenopus embryos will be a very powerful tool for temporal analysis of gene
      function and for studying molecular mechanisms of vertebrate organogenesis.

PMID- 10899006
TI  - The dynamic behavior of the APC-binding protein EB1 on the distal ends of
      microtubules.
AB  - Adenomatous polyposis coli protein (APC) is a well-characterized tumor suppressor
      protein [1] [2] [3]. We previously showed that APC tagged with green fluorescent
      protein (GFP) in Xenopus A6 epithelial cells moves along a subset of microtubules
      and accumulates at their growing plus ends in cell extensions [4]. EB1, which was
      identified as an APC-binding protein by yeast two-hybrid analysis [5], was also
      reported to be associated with microtubules [6] [7] [8]. To examine the
      interaction between APC and EB1 within cells, we compared the dynamic behavior of
      EB1-GFP with that of APC-GFP in A6 transfectants. Time-lapse microscopy of live
      cells at interphase revealed that EB1-GFP was concentrated at all of the growing
      microtubule ends throughout the cytoplasm and abruptly disappeared from the ends
      when microtubules began to shorten. Therefore, EB1 appeared to be co-localized
      and interact with APC on the growing ends of a subset of microtubules. When APC
      GFP was overexpressed, endogenous EB1 was recruited to APC-GFP, which accumulated
      in large amounts on microtubules. On the other hand, when microtubules were
      disassembled by nocodazole, EB1 was not co-localized with APC-GFP, which was
      concentrated along the basal plasma membrane. During mitosis, APC appeared to be
      dissociated from microtubules, whereas EB1-GFP continued to concentrate at
      microtubule growing ends. These findings showed that the APC-EB1 interaction is
      regulated within cells and is allowed near the ends of microtubules only under
      restricted conditions.

PMID- 10899007
TI  - Differences between the clearance of apoptotic cells by professional and non
      professional phagocytes.
AB  - Both professional and non-professional phagocytes [1] participate in clearing the
      massive numbers of cells that undergo apoptosis during animal development [2],
      but it is not known how they divide this task. Using time-lapse recordings of
      cells in culture, we show that professional phagocytes (brain macrophages or
      microglia) are highly motile, ingest apoptotic cells immediately, and digest them
      quickly. Non-professionals such as BHK and lens epithelial cells are sessile,
      often recognize apoptotic cells as soon as they die by showing characteristic
      palpating movements, but delay ingestion until several hours later. By pre-ageing
      apoptotic cells, we show that this delay is because the apoptotic cells must
      undergo further changes before non-professionals can ingest them. The difference
      was also apparent in vivo, using immunofluorescence and electron microscopy of
      the developing central nervous system. This arrangement favours prompt clearance
      by professionals if present in adequate numbers; if they are scarce, however, non
      professional bystanders will reluctantly clear the apoptotic cells.

PMID- 10899008
TI  - A region of the vertebrate neural plate in which neighbouring cells can adopt
      neural or epidermal fates.
AB  - Cells in the neurogenic region of the fly, Drosophila melanogaster, become either
      neural stem cells or epidermis and the selection of the former requires the
      activity of the proneural genes [1]. In contrast, it is commonly thought that all
      cells in the vertebrate neural plate contribute to the neural tube and that
      consequently there is no need for the selection of individual neural precursors
      (e.g., [2]). Here we present a detailed fate map of the chick caudal neural plate
      (CNP), a cell population that generates the posterior hindbrain and spinal cord.
      We show that this is a unique region of the neural plate where neighbouring cells
      can contribute to neural tube or epidermis. Further, neural tube precursors leave
      the CNP in an approximate rostro-caudal order and give rise to discrete portions
      of the neural tube where they or their progeny behave as neural stem cells [3].
      Our data suggest that neural and epidermal cell fates are acquired on a cell-by
      cell basis within the CNP and thus in a manner strikingly similar to that in the
      fly. Indeed, the assignment of neural cell fate in this region may prove to be
      mediated by the functional homologue of the fly proneural genes (chick achaete
      scute homologue 4, cash4), which is expressed heterogeneously within this cell
      population [4].

PMID- 10899009
TI  - TOR signaling regulates microtubule structure and function.
AB  - The functional diversity and structural heterogeneity of microtubules are largely
      determined by microtubule-associated proteins (MAPs) [1] [2]. Bik1p (bilateral
      karyogamy defect protein) is one of the MAPs required for microtubule assembly,
      stability and function in cell processes such as karyogamy and nuclear migration
      and positioning in the yeast Saccharomyces cerevisiae [3]. The macrocyclic
      immunosuppressive antibiotic rapamycin, complexed with its binding protein
      FKBP12, binds to and inhibits the target of rapamycin protein (TOR) in yeast [4]
      [5]. We report here that TOR physically interacts with Bik1p, the yeast homolog
      of human CLIP-170/Restin [6] [7]. Inhibition of TOR by rapamycin significantly
      affects microtubule assembly, elongation and stability. This function of TOR is
      independent of new protein synthesis. Rapamycin also causes defects in spindle
      orientation, nuclear movement and positioning, karyogamy and chromosomal
      stability, defects also found in the bikDelta mutant. Our data suggest a role for
      TOR signaling in regulating microtubule stability and function, possibly through
      Bik1p.

PMID- 10899010
TI  - Functional association of CTCF with the insulator upstream of the H19 gene is
      parent of origin-specific and methylation-sensitive.
AB  - In mammals, a subset of genes inherit gametic marks that establish parent of
      origin-dependent expression patterns in the soma ([1] and references therein).
      The currently most extensively studied examples of this phenomenon, termed
      genomic imprinting, are the physically linked Igf2 (insulin-like growth factor
      II) and H19 genes, which are expressed mono-allelically from opposite parental
      alleles [1] [2]. The repressed status of the maternal Igf2 allele is due to cis
      elements that prevent the H19 enhancers [3] from accessing the Igf2 promoters on
      the maternal chromosome [4] [5]. A differentially methylated domain (DMD) in the
      5' flank of H19 is maintained paternally methylated and maternally unmethylated
      [6] [7]. We show here by gel-shift and chromatin immunopurification analyses that
      binding of the highly conserved multivalent factor CTCF ([8] [9] and references
      therein) to the H19 DMD is methylation-sensitive and parent of origin-dependent.
      Selectively mutating CTCF-contacting nucleotides, which were identified by
      methylation interference within the extended binding sites initially revealed by
      nuclease footprinting, abrogated the H19 DMD enhancer-blocking property. These
      observations suggest that molecular mechanisms of genomic imprinting may use an
      unusual ability of CTCF to interact with a diverse spectrum of variant target
      sites, some of which include CpGs that are responsible for methylation-sensitive
      CTCF binding in vitro and in vivo.

PMID- 10899011
TI  - A second timeless gene in Drosophila shares greater sequence similarity with
      mammalian tim.

PMID- 10899012
TI  - The mighty mite

PMID- 10899013
TI  - The basal ganglia.

PMID- 10899014
TI  - Kinetochores.

PMID- 10899015
TI  - The gene pool

PMID- 10899016
TI  - Unconscious secrets

PMID- 10899017
TI  - The immunogenicity of human and murine cytomegaloviruses.
AB  - Cytomegaloviruses are strictly host-species-specific. During an aeon of co
      evolution, virus and host have found an arrangement: the productive and
      cytopathogenic cycle of viral gene expression is held in check by the host's
      immune response. As a consequence, cytomegalovirus disease is restricted to the
      immunocompromised host. The virus has evolved strategies to avoid its elimination
      and eventually hides itself in a silent state, referred to as 'viral latency'.
      Redundant molecular mechanisms have been identified by which cytomegaloviruses
      interfere with antigen presentation pathways to 'evade' immune control. In the
      annual period covered by this review, the IE1 protein was revisited as an
      immunodominant antigen of human cytomegalovirus and the identification of a first
      antigenic early-phase peptide of murine cytomegalovirus that escapes viral
      immunosubversive mechanisms may initiate a period of research on the immune
      control of cytomegaloviruses 'beyond immune evasion'.

PMID- 10899018
TI  - Immunological concepts of vaccine adjuvant activity.

PMID- 10899019
TI  - Immune responses in tuberculosis.
AB  - The initial interaction of Mycobacterium tuberculosis with phagocytes through
      Toll-like receptors can affect induction of the adaptive response by inflammatory
      cytokine production, as well as begin the process of bacterial containment by
      induction of antimycobacterial functions. Advances in T cell research in
      tuberculosis include identification of antigens recognized by CD8(+) T cells in
      infected hosts, elucidation of antimycobacterial mechanisms of T cells and the
      discovery of CD8(+) T cells that recognize antigens presented by a variety of non
      classical molecules.

PMID- 10899020
TI  - Functions of tetramer-stained HIV-specific CD4(+) and CD8(+) T cells.
AB  - Significant insight has been gained into constraints on the sensitivity and
      specificity of staining with class I tetramers. The function of the populations
      that are defined varies with the clinical situation. Insight has also been gained
      into the determinants of the CD8(+) T cell response during primary and chronic
      HIV infection. Human class II tetramers have been synthesised but their role in
      defining CD4(+) T cell function in HIV infection remains to be determined.

PMID- 10899021
TI  - Protection or damage: a dual role for the virus-specific cytotoxic T lymphocyte
      response in hepatitis B and C infection?
AB  - During infection with hepatitis B or C viruses, cytotoxic T lymphocytes (CTLs)
      have been implicated as both the mediators of protection and the principal
      effectors of liver pathology. Recent studies have allowed an investigation of the
      relationship between virus-specific CTL responses, liver damage and viral
      replication. In the presence of an efficient virus-specific CTL response, a
      scenario is emerging where inhibition of viral replication can be independent of
      liver pathology. We discuss the possibility that an inadequate CTL response-
      unable to control viral replication - may contribute to liver pathology not only
      directly but also via the recruitment of non-virus-specific T cells.

PMID- 10899022
TI  - The immunology of malaria infection.
AB  - As global malaria mortality increases the urgency for vaccine development,
      analysis of immune responses in naturally exposed populations is providing clues
      to the nature of protective immunity. Recently, sophisticated immune evasion
      strategies adopted by the parasite have been analysed at the molecular level.
      More immunogenic vaccination strategies have been identified, providing renewed
      optimism that effective malaria control through vaccination should be feasible.

PMID- 10899023
TI  - Cytokines and T cells in host defense.
AB  - Soluble and cell-bound ligands profoundly influence the differentiative fate of
      lymphocytes during an immune response. Recent advances have been made in
      understanding the role of cytokine signals and costimulatory signals in the
      regulation of T cell responses associated with resistance or susceptibility to
      infection. There has also been recent progress in defining the requirements for
      the generation and maintenance of immunologic memory, a critical component of
      adaptive immunity.

PMID- 10899024
TI  - Modulation of chemokines by poxvirus infections.
AB  - Viruses that successfully replicate within the host have devised strategies to
      subvert or evade the challenges posed by the innate and adaptive immune
      responses. Many investigators are now beginning to dissect the diverse and
      complex interactions involving chemokines, chemokine receptors and viral
      infection. In recent years, much attention has been focused on the role of
      chemokines in antiviral defense.

PMID- 10899025
TI  - Immunity to Listeria infection.
AB  - Infection with Listeria monocytogenes is a well studied model for understanding
      host resistance to intracellular bacteria. Recent advances in the study of
      Listeria have carefully quantitated the response of CD8(+) T cells to infection
      and analyzed the effector functions of these cells in vivo. A surprising role for
      antibody in mediating resistance to Listeria has also recently emerged, providing
      new insight into the mechanisms of host defense.

PMID- 10899026
TI  - DNA vaccines: a key for inducing long-term cellular immunity.
AB  - Over the past few years, major advances in several areas of immunology have
      provided a foundation for the rational design of vaccines against diseases
      requiring cellular immunity. Among these advances are the cellular mechanisms by
      which DNA vaccines can sustain long-term humoral and cellular immunity.

PMID- 10899027
TI  - The immune response to HTLV-I.
AB  - A strong cytotoxic T lymphocyte response to HTLV-I protects against the
      associated inflammatory disease of the central nervous system, HAM/TSP (HTLV-I
      associated myelopathy/tropical spastic paraparesis), by reducing the proviral
      load of HTLV-I; however, when the proviral load exceeds a threshold level, HTLV-I
      specific cytotoxic T lymphocytes could contribute to inflammation.

PMID- 10899028
TI  - The role of CD4(+) T helper cells in the cytotoxic T lymphocyte response to HIV
      1.
AB  - Virus-specific CD4(+) T cell help and CD8(+) cytotoxic T cell (CTL) responses are
      critical for the maintenance of effective immunity in chronic viral infections.
      HIV-1 infection presents a unique situation in which HIV-1-specific T helper cell
      responses are characteristically impaired and virus-specific CTLs wane over time
      as disease progresses; a relationship exists between T cell help and CTL
      responses in HIV-1 infection.

PMID- 10899029
TI  - Mutations in the gene for the IL-7 receptor result in T(-)B(+)NK(+) severe
      combined immunodeficiency disease.
AB  - Recently, two SCID (severe combined immunodeficiency disease) patients with
      greatly diminished T cells but normal or increased numbers of B and NK cells (T(
      )B(+)NK(+) SCID) were found to have mutations in the gene for the IL-7 receptor.
      This has established a major role for IL-7-receptor-dependent signaling in T cell
      development in humans and probably explains the diminished T cell numbers seen in
      patients with X-linked SCID or SCID that results from Jak3-deficiency.

PMID- 10899030
TI  - The gene defective in X-linked lymphoproliferative disease controls T cell
      dependent immune surveillance against Epstein-Barr virus.
AB  - Our understanding of the X-linked lymphoproliferative syndrome (XLP) has advanced
      significantly in the past two years. The gene that is aberrant in the condition -
      SH2D1A/SAP, which encodes SAP (signaling lymphocytic activation molecule [SLAM]
      associated protein) - was cloned, the crystal structure of its product was solved
      and insights into the signaling mechanisms of this small SH2-domain-containing
      protein via the cell surface receptors SLAM and 2B4 have been provided. SAP
      mutation, and not Epstein-Barr virus infection per se, may be critical for XLP.

PMID- 10899031
TI  - The CD4(+) T cell response to HIV-1.
AB  - Although virus-specific CD4(+) T cells have proven to be a critical component of
      the immunologic control of chronic viral infections in a number of models, the
      role and even the existence of HIV-1-specific CD4(+) T cells in human HIV-1
      infection has been controversial. Recent advances in quantifying and functionally
      characterizing HIV-1-specific T cells may shed light on the participation of
      these cells in anti-HIV-1 host defense.

PMID- 10899032
TI  - Costimulation in antiviral immunity: differential requirements for CD4(+) and
      CD8(+) T cell responses.
AB  - A key step toward improving vaccines is understanding the molecular interactions
      responsible for inducing antiviral T cell responses. An emerging theme from
      recent studies is that CD4(+) and CD8(+) T cell responses require distinct
      costimulatory pathways for activation. In addition, these costimulatory
      interactions can play a crucial role during the death phase of the T cell
      response and determine the number of effector T cells that survive to become
      memory T cells.

PMID- 10899033
TI  - The function of type I interferons in antimicrobial immunity.
AB  - Type I interferons (IFN-alpha and IFN-beta) were originally described as potent
      antiviral substances, which are produced upon infection of animal cells with
      viruses. Despite a large body of literature that has accumulated during the past
      25 years, their regulatory function in the immune system is still much less
      appreciated. Recent studies have highlighted the production of type I IFNs, their
      function in the immune response to infectious agents and the target cells of
      these interferons. Type I IFNs clearly affect the release of proinflammatory
      cytokines or nitric oxide by dendritic cells and macrophages, the capacity of
      type II interferon (IFN-gamma) to activate phagocytes, the differentiation of T
      helper cells and the innate control of non-viral pathogens.

PMID- 10899034
TI  - TNFRSF1A mutations and autoinflammatory syndromes.
AB  - The autoinflammatory syndromes are systemic disorders characterized by apparently
      unprovoked inflammation in the absence of high-titer autoantibodies or antigen
      specific T lymphocytes. One such illness, TNF-receptor-associated periodic
      syndrome (TRAPS), presents with prolonged attacks of fever and severe localized
      inflammation. TRAPS is caused by dominantly inherited mutations in TNFRSF1A
      (formerly termed TNFR1), the gene encoding the 55 kDa TNF receptor. All known
      mutations affect the first two cysteine-rich extracellular subdomains of the
      receptor, and several mutations are substitutions directly disrupting conserved
      disulfide bonds. One likely mechanism of inflammation in TRAPS is the impaired
      cleavage of TNFRSF1A ectodomain upon cellular activation, with diminished
      shedding of the potentially antagonistic soluble receptor. Preliminary experience
      with recombinant p75 TNFR-Fc fusion protein in the treatment of TRAPS has been
      favorable.

PMID- 10899035
TI  - Comparison of cerebrovascular effects of intravenous cocaine injection in fetal,
      newborn, and adult sheep.
AB  - Cocaine may cause stroke, intracranial hemorrhage, seizures, and neurobehavioral
      abnormalities in fetuses, newborns, and adults, and there could be developmental
      and/or species differences in mechanisms for these cocaine-induced
      cerebrovascular effects. To evaluate developmental differences in responses to
      cocaine, we compared the cerebrovascular and metabolic responses to a 2 mg/kg iv
      cocaine dose in unanesthetized fetal (n = 8, previously reported, direct fetal
      injection), newborn (n = 6), and adult (n = 12) sheep. We measured cerebral blood
      flow, mean arterial blood pressure, and arterial and venous O(2) content, and we
      calculated cerebral O(2) consumption and cerebral vascular resistance at baseline
      and at 30 s and at 5, 15, and 60 min after cocaine injection. Cerebral blood flow
      increased 5 min after injection in the fetus and newborn, but not until 15 min in
      the adult. In the fetus, cocaine caused a transient cerebral vasoconstriction at
      30 s; in all three groups, cocaine caused cerebral vasodilation, which was
      delayed in the adult. Cerebral metabolic O(2) consumption increased 5 min after
      injection in the fetus and newborn, but not until 15 min after injection in the
      adult. Arterial O(2) content decreased 5 min after injection in the fetus and 15
      min after injection in the adult. We speculate that clinical differences in
      response to cocaine injection may be explained, in part, by these developmental
      differences in the cerebrovascular and metabolic responses to cocaine.

PMID- 10899036
TI  - Reactive oxygen species may contribute to reduced endothelium-dependent dilation
      in rats fed high salt.
AB  - In normotensive rats, an increase in dietary salt leads to decreased arteriolar
      responsiveness to acetylcholine (ACh) because of suppressed local nitric oxide
      (NO) activity. We evaluated the possibility that generation of reactive oxygen
      species in the arteriolar wall is responsible for this loss of NO activity.
      Arteriolar responses to iontophoretically applied ACh were examined in the
      superfused spinotrapezius muscle of Sprague-Dawley rats fed a low-salt (LS;
      0.45%) or high-salt diet (HS; 7%) for 4-5 wk. Responses to ACh were significantly
      depressed in HS rats but returned to normal in the presence of the oxidant
      scavengers superoxide dismutase + catalase or 2,2,6, 6-tetamethylpiperidine-N
      oxyl (TEMPO) + catalase. Arteriolar responses to the NO donor sodium
      nitroprusside were similar in HS and LS rats. Arteriolar and venular wall oxidant
      activity, as determined by reduction of tetranitroblue tetrazolium, was
      significantly greater in HS rats than in LS rats. Exposure to TEMPO + catalase
      reduced microvascular oxidant levels to normal in HS rats. These data suggest
      that a high-salt diet leads to increased generation of reactive oxygen species in
      striated muscle microvessels, and this increased oxidative state may be
      responsible for decreased endothelium-dependent responses associated with high
      salt intake.

PMID- 10899037
TI  - Modulation of arrhythmias by isoproterenol in a rabbit heart model of d-sotalol
      induced long Q-T intervals.
AB  - Sympathetic influences have been implicated in arrhythmias associated with both
      congenital and acquired long Q-T intervals. We recorded epicardial electrograms,
      a left ventricular endocardial monophasic action potential (MAP), and a bipolar
      electrocardiogram in 23 isolated rabbit hearts. Spontaneous focal arrhythmias
      appeared within 8-18 min following 92 microM d-sotalol in 15 of 23 hearts. The
      epicardial activation-recovery interval was shorter at baseline and increased to
      a significantly greater degree after d-sotalol administration in the hearts that
      developed focal activity. The standard deviation of the activation-recovery
      interval of the epicardial sites also increased. With the addition of 0.01 microM
      isoproterenol, the incidence of focal activity increased, and its mean cycle
      length was shortened by 7%. Also, myocardial recovery time in the epicardium was
      shortened to a greater degree than the endocardial MAP duration. It did not alter
      local epicardial heterogeneity of recovery but did increase the regional
      dispersion between epicardial recovery times, and the endocardial MAP duration.
      Therefore, beta-adrenergic stimulation in the presence of d-sotalol favors the
      appearance of arrhythmias by increasing the propensity for closely coupled focal
      activity and the temporal dispersion of recovery.

PMID- 10899038
TI  - Diacylglycerol and fatty acids synergistically increase cardiomyocyte contraction
      via activation of PKC.
AB  - Lipid signaling pathways are thought to play a prominent role in transducing
      extracellular signals into contractile responses in cardiac muscle. Two putative
      lipid messengers, diacyglycerol and arachidonic acid, can be generated via
      distinct phospholipases in separate signaling pathways, but certain stimuli cause
      them to be elevated in parallel. We tested the hypothesis that these lipids
      function as comessengers in ventricular myocytes by activating protein kinase C
      (PKC). In previous work, we demonstrated that the diacylglycerol analog
      dioctanoylglycerol (diC(8)) can be stimulatory or inhibitory toward myocyte
      twitches depending on how it is applied. Here we report that arachidonic acid and
      other cis-unsaturated fatty acids (UFA), at concentrations too low for direct
      effects, synergistically enhance the stimulatory effects of diC(8) and convert
      inhibitory effects of diC(8) into stimulation of myocyte twitches. Intracellular
      Ca(2+) transients changed in parallel with twitch amplitude, suggesting
      regulation of Ca(2+) homeostasis by these lipids. cis-UFA also interacted
      synergistically with the PKC activator phorbol 12-myristate 13-acetate to promote
      positive inotropic responses. Responses were blocked by the PKC antagonists
      chelerythrine chloride, bisindolylmaleimide, and Go-6976. DiC(8) and arachidonic
      acid also synergistically translocated PKC-epsilon and PKC-alpha in intact
      myocytes. We propose that PKC integrates diacylglycerol and cis-UFA signals in
      the heart, resulting in preferential activation of positive inotropic mechanisms.

PMID- 10899039
TI  - Coexpression with beta(1)-subunit modifies the kinetics and fatty acid block of
      hH1(alpha) Na(+) channels.
AB  - Voltage-gated cardiac Na(+) channels are composed of alpha- and beta(1)-subunits.
      In this study beta(1)-subunit was cotransfected with the alpha-subunit of the
      human cardiac Na(+) channel (hH1(alpha)) in human embryonic kidney (HEK293t)
      cells. The effects of this coexpression on the kinetics and fatty acid-induced
      suppression of Na(+) currents were assessed. Current density was significantly
      greater in HEK293t cells coexpressing alpha- and beta(1)-subunits (I(Na,alpha
      beta)) than in HEK293t cells expressing alpha-subunit alone (I(Na,alpha)).
      Compared with I(Na,alpha), the voltage-dependent inactivation and activation of
      I(Na,alpha beta) were significantly shifted in the depolarizing direction. In
      addition, coexpression with beta(1)-subunit prolonged the duration of recovery
      from inactivation. Eicosapentaenoic acid [EPA, C20:5(n-3)] significantly reduced
      I(Na,alpha beta) in a concentration-dependent manner and at 5 microM shifted the
      midpoint voltage of the steady-state inactivation by -22 +/- 1 mV. EPA also
      significantly accelerated channel transition from the resting state to the
      inactivated state and prolonged the recovery time from inactivation.
      Docosahexaenoic acid [C22:6(n-3)], alpha-linolenic acid [C18:3(n-3)], and
      conjugated linoleic acid [C18:2(n-6)] at 5 microM significantly inhibited both
      I(Na,alpha beta) and I(Na,alpha.) In contrast, saturated and monounsaturated
      fatty acids had no effects on I(Na,alpha beta). This finding differs from the
      results for I(Na,alpha), which was significantly inhibited by both saturated and
      unsaturated fatty acids. Our data demonstrate that functional association of
      beta(1)-subunit with hH1(alpha) modifies the kinetics and fatty acid block of the
      Na(+) channel.

PMID- 10899040
TI  - Diameter changes in skeletal muscle venules during arterial pressure reduction.
AB  - Previous studies in skeletal muscle have shown a substantial (>100%) increase in
      venous vascular resistance with arterial pressure reduction to 40 mmHg, but a
      microcirculatory study showed no significant venular diameter changes in the
      horizontal direction during this procedure. To examine the possibility of venular
      collapse in the vertical direction, a microscope was placed horizontally to view
      a vertically mounted rat spinotrapezius muscle preparation. We monitored the
      diameters of venules (mean diameter 73. 8 +/- 37.0 microm, range 13-185 microm)
      oriented horizontally and vertically with a video system during acute arterial
      pressure reduction by hemorrhage. Our analysis showed small but significant (P <
      0.0001) diameter reductions of 1.0 +/- 2.5 microm and 1.8 +/- 3. 1 microm in
      horizontally and vertically oriented venules, respectively, upon reduction of
      arterial pressure from 115.0 +/- 26. 3 to 39.8 +/- 12.3 mmHg. The venular
      responses were not different after red blood cell aggregation was induced by
      Dextran 500 infusion. We conclude that diameter changes in venules over this
      range of arterial pressure reduction are isotropic and would likely increase
      venous resistance by <10%.

PMID- 10899041
TI  - SHR Y chromosome enhances the nocturnal blood pressure in socially interacting
      rats.
AB  - Our objective was to test the hypothesis that nocturnal mean arterial pressure
      (MAP), heart rate (HR), and activity would be increased in 1) colony over
      individually caged rats and 2) the spontaneously hypertensive rat (SHR) Y
      chromosome strain (SHR/y colony) compared with Wistar-Kyoto (WKY) rats. MAP, HR,
      and activity were monitored using radiotelemetry. The nocturnal MAP rise
      expressed as the percentage change in MAP from light to dark was increased (P <
      0.05) in the SHR/y colony. The SHR Y chromosome increased MAP in both the colony
      and caged groups compared with WKY (P < 0.001). The SHR/y colony animals spent
      23% of a 24-h period at a MAP >120 mmHg, whereas the WKY colony animals spent 2%
      of a 24-h period in this range. The MAP of the SHR/y colony on clonidine was
      reduced (P < 0.001) to WKY baseline values. Activity but not HR was increased (P
      < 0.01) in the WKY and SHR/y colonies compared with caged animals. In conclusion,
      colony housing and the SHR Y chromosome increased MAP compared with individually
      caged housing.

PMID- 10899043
TI  - Mechanism of effect of extracellular pH on L-type Ca(2+) channel currents in
      human mesenteric arterial cells.
AB  - Extracellular pH (pH(o)) influences vasoconstriction partly by modulating Ca(2+)
      influx through voltage-gated Ca(2+) channels in the vasculature. The mechanism of
      this effect of pH(o) is, however, controversial. Using the whole cell voltage
      clamp technique, we examined the influence of pH(o) on L-type Ca(2+) channel
      currents in isolated human mesenteric arterial myocytes. Acidification to pH 6.2
      and alkalinization to 8.2 from 7.2 decreased by approximately 50% and increased
      by 25-30%, respectively, the peak amplitude of Ca(2+) and Ba(2+) currents (1.5
      and 10 mM), with an apparent pK(a) of 6.8. Activation and inactivation of Ca(2+)
      and Ba(2+) currents were shifted toward positive membrane voltages during
      acidification and in the opposite direction during alkalinization. The
      relationship between the current amplitude and shifts in the gating parameters in
      solutions of different pH(o) conformed closely to that predicted by the Gouy
      Chapman model, in which the divalent cation concentration at the outer surface of
      the membrane varies with the extent to which protons neutralize the membrane
      surface potential.

PMID- 10899042
TI  - Neurotransmission of autonomic components of aortic baroreceptor afferents in the
      NTS of awake rats.
AB  - The effect of sequential blockade of N-methyl-D-aspartic acid (NMDA) receptors
      with DL-2-amino-5-phosphonopentanoic acid (AP-5) and non-NMDA receptors with 6,7
      dinitroquinoxaline-2,3 dione (DNQX) in the nucleus tractus solitarii (NTS) on the
      cardiovascular responses to electrical stimulation (ES) of the aortic depressor
      nerve (ADN) was evaluated in awake rats. Two protocols were used. In protocol 1,
      bilateral microinjection of AP-5 into the NTS (n = 7) reduced the hypotensive
      response to ES of the ADN; subsequent microinjection of DNQX produced additional
      reduction in this response. AP-5 reduced the bradycardic response, and DNQX
      almost abolished this response. In protocol 2, bilateral microinjection of DNQX
      into the NTS (n = 6) reduced the hypotensive response, and subsequent
      microinjection of AP-5 significantly reduced this response. DNQX produced a
      significant reduction in bradycardic response, and AP-5 abolished this response.
      The data indicate that processing of the parasympathetic component of the NTS
      aortic baroreceptor afferents is mediated by both NMDA and non-NMDA receptors,
      whereas processing of the sympathoinhibitory component seems to be only partially
      mediated by ionotropic receptors.

PMID- 10899044
TI  - Effects of losartan treatment on cardiac autonomic control during volume loading
      in patients with DCM.
AB  - This study evaluated the effect of angiotensin II receptor blockade on cardiac
      autonomic control adaptation and urine output in response to acute isotonic
      volume load in patients with idiopathic dilated cardiomyopathy (DCM) and
      asymptomatic to mildly symptomatic heart failure. Left ventricular volumes and
      heart rate variability measurements were assessed at baseline and during
      intravenous saline load in 14 patients before and after 2 mo of losartan
      treatment. After losartan treatment, blood pressure values were lower, whereas
      left ventricular ejection fraction was higher (F = 79, P < 0.001), than before
      treatment. During saline load, ejection fraction decreased before losartan
      treatment (F = 5.6, P < 0.05) but did not change after treatment. Urinary volume,
      unchanged during saline load in untreated patients, increased after losartan (F =
      9.38, P < 0. 001). Time-domain measurements that represent vagal modulation of
      heart rate (root-mean-square successive differences and percentage of differences
      between successive R-R intervals >50 ms) decreased during saline load in
      untreated patients (F = 3.1, P < 0.05 and F = 6.5, P < 0.01, respectively), but
      not after losartan. Similarly, a decrease in very low frequency (F = 3.2, P <
      0.05), low-frequency (F = 2.9, P < 0.05), and high-frequency power (F = 6.1, P <
      0.01) after saline load was observed only in untreated patients. In patients with
      DCM, losartan treatment improves the cardiac autonomic adaptation and increases
      urine output in response to volume overload.

PMID- 10899045
TI  - Effect of selective ET(A) receptor blockade on natriuretic peptide gene
      expression in DOCA-salt hypertension.
AB  - To determine the role of endothelin-1 (ET-1) in the upregulation of atrial
      natriuretic factor (ANF) and brain natriuretic peptide (BNP) observed in
      deoxycorticosterone acetate (DOCA)-salt hypertension, the selective ET-1 type-A
      receptor (ET(A)) antagonist ABT-627 was chronically administered to normal
      controls and hypertensive rats. Chronic ET(A) blockade in DOCA-salt-treated rats
      prevented the increase in blood pressure and circulating natriuretic protein (NP)
      levels and partially prevented left ventricular hypertrophy. The changes observed
      in NP gene expression in the atria were not affected by ABT-627. In the
      ventricles, ABT-627 reduced NP gene expression. Rats receiving the ET(A)
      antagonist alone showed reduced left ventricular NP gene expression. ABT-627 did
      not affect ventricular collagen III gene expression but enhanced left ventricular
      alpha-myosin heavy chain expression. These findings suggest that in vivo,
      ventricular but not atrial NP production is regulated by ET-1. This difference in
      response between atrial and ventricular NP gene expression to ET(A) receptor
      blockade is similar to that observed by us after applying angiotensin-converting
      enzyme inhibitors in other hypertensive models. In general therefore, atrial NP
      gene expression may not be as sensitive to the endocrine environment as is
      ventricular NP gene expression.

PMID- 10899046
TI  - Transmural distribution of FDG uptake in stunned myocardium.
AB  - Fasting [(18)F]fluoro-2-deoxyglucose (FDG) uptake is increased in viable,
      chronically dysfunctional myocardium, but the relationship to acute episodes of
      ischemia remains undefined. To investigate FDG uptake in acute stunning,
      chronically instrumented pigs (n = 9) and sham controls (n = 8) were studied
      while in a fasted, closed-chest, anesthetized state. One-hour partial occlusion
      reduced subendocardial flow from 1.24 +/- 0.14 to 0.35 +/- 0.06 ml. min(-1). g(
      1) and wall thickening from 16.8 +/- 2.1 to 3.7 +/- 0.7%. Regional function
      remained depressed during reperfusion (8.3 +/- 1. 4%) despite the return of flow
      to resting levels. Triphenyl tetrazolium chloride staining showed no irreversible
      injury. FDG uptake in stunned myocardium was variably increased and averaged 1. 5
      fold higher than that of normal regions, with no consistent transmural variation.
      Subgroup analysis showed that variability in FDG uptake was related to
      alterations in insulin levels that varied directly with ischemic risk region.

PMID- 10899047
TI  - Cumulative plot of heart rate variability spectrum assesses kinetics of action of
      cholinergic drugs in rats.
AB  - A new approach to assess autonomic nervous system (ANS) activity and its response
      to drug action is presented. Our approach is based on the use of a cumulative
      plot of data obtained by power spectral analysis of heart rate variability, in
      defined frequency bands, during short time epochs (e.g., 2 min in rats). The
      substantial temporal variability in power evolving from the constant balancing
      nature of the ANS activity is minimized by this approach and produces a
      measurable index of ANS activity vs. time. The cumulative plot emphasizes the
      temporal response pattern of different components of the ANS and thereby
      facilitates the investigation of the kinetics of action of drugs affecting the
      ANS. We used this method to measure the activity of cholinergic drugs in freely
      moving Sabra rats. Bolus atropine doses between 0.5 and 2 mg/kg produced a
      similar magnitude of effect, reduction of the ascending slope by 0. 003 power
      units/h, whereas the duration of this effect was dose dependent. A lower atropine
      dose (0.1 mg/kg) or 0.5 mg/kg scopolamine elevated the slope (0.074 and 0.054
      power units/h for 206 and 216 min, respectively). The method was used similarly
      to assess the interaction between cholinergic drugs. Pretreatment with
      pyridostigmine produced temporal blockage of the anticholinergic activity of
      atropine.

PMID- 10899048
TI  - Cardiac interstitial bradykinin release during ischemia is enhanced by ischemic
      preconditioning.
AB  - Ischemic preconditioning is known to protect the myocardium from ischemia
      reperfusion injury. We examined the transmural release of bradykinin during
      myocardial ischemia and the influence of ischemic preconditioning on bradykinin
      release during subsequent myocardial ischemia. Myocardial ischemia was induced by
      occlusion of the left anterior descending coronary artery in anesthetized cats.
      Cardiac microdialysis was performed by implantation and perfusion of dialysis
      probes in the epicardium and endocardium. In eight animals, bradykinin release
      was greater in the endocardium than in the epicardium (14.4 +/- 2.8 vs. 7.3 +/-
      1.7 ng/ml, P < 0.05) during 30 min of ischemia. In seven animals subjected to
      preconditioning, myocardial bradykinin release was potentiated significantly from
      2.4 +/- 0.6 ng/ml during the control period to 23.1 +/- 2.5 ng/ml during 30 min
      of myocardial ischemia compared with the non-preconditioning group (from 2.7 +/-
      0.6 to 13.4 +/- 1.9 ng/ml, P < 0.05, n = 6). Thus this study provides further
      evidence that transmural gradients of bradykinin are produced during ischemia.
      The results also suggest that ischemic preconditioning enhances bradykinin
      release in the myocardial interstitial fluid during subsequent ischemia, which is
      likely one of the mechanisms of cardioprotection of ischemic preconditioning.

PMID- 10899049
TI  - Short-term variability of pulse pressure and systolic and diastolic time in heart
      transplant recipients.
AB  - In heart transplant recipients (HTR), short-term systolic blood pressure
      variability is preserved, whereas heart rate variability is almost abolished.
      Heart period is the sum of left ventricular ejection time (LVET) and diastolic
      time (DT). In the present time-domain prospective study, we tested the hypothesis
      that short-term fluctuations in aortic pulse pressure (PP) in HTR were related to
      fluctuations in LVET. Seventeen male HTR (age 48 +/- 6 yr) were studied 16 +/- 11
      mo after transplantation. Aortic root pressure was obtained over a 15-s period
      using a micromanometer both at rest (n = 17) and following the cold pressor test
      (CPT, n = 14). There was a strong positive linear relationship between beat-to
      beat LVET and beat-to-beat PP in all patients at rest and in 13 of 14 patients
      following CPT (each P < 0.01). The slope of this relationship showed little
      scatter both at rest (0.34 +/- 0.07 mmHg/ms) and following CPT (0.35 +/- 0.09
      mmHg/ms, P = not significant). Given the essentially fixed heart period, DT
      varied inversely with LVET. As a result, in 13 of 17 HTR at rest and in 12 of 14
      HTR following CPT, there was a negative linear relationship between beat-to-beat
      PP and DT. In conclusion, our short-term time-domain study demonstrated a strong
      positive linear relationship between LVET and blood pressure variability in male
      HTR. We also identified a subgroup of HTR in whom there was a mismatch between PP
      and DT.

PMID- 10899050
TI  - Existence of a transient outward K(+) current in guinea pig cardiac myocytes.
AB  - A novel transient outward K(+) current that exhibits inward-going rectification
      (I(to.ir)) was identified in guinea pig atrial and ventricular myocytes. I(to.ir)
      was insensitive to 4-aminopyridine (4-AP) but was blocked by 200 micromol/l
      Ba(2+) or removal of external K(+). The zero current potential shifted 51-53
      mV/decade change in external K(+). I(to.ir) density was twofold greater in
      ventricular than in atrial myocytes, and biexponential inactivation occurs in
      both types of myocytes. At -20 mV, the fast inactivation time constants were 7.7
      +/- 1.8 and 6.1 +/- 1.2 ms and the slow inactivation time constants were 85.1 +/-
      14.8 and 77.3 +/- 10.4 ms in ventricular and atrial cells, respectively. The
      midpoints for steady-state inactivation were -36.4 +/- 0.3 and -51.6 +/- 0.4 mV,
      and recovery from inactivation was rapid near the resting potential (time
      constants = 7.9 +/- 1.9 and 8.8 +/- 2.1 ms, respectively). I(to.ir) was detected
      in Na(+)-containing and Na(+)-free solutions and was not blocked by 20 nmol/l
      saxitoxin. Action potential clamp revealed that I(to.ir) contributed an outward
      current that activated rapidly on depolarization and inactivated by early phase 2
      in both tissues. Although it is well known that 4-AP-sensitive transient outward
      current is absent in guinea pig, this Ba(2+)-sensitive and 4-AP-insensitive K(+)
      current has been overlooked.

PMID- 10899051
TI  - Changes in ionic currents and beta-adrenergic receptor signaling in hypertrophied
      myocytes overexpressing G alpha(q).
AB  - Transgenic overexpression of G alpha(q) causes cardiac hypertrophy and depressed
      contractile responses to beta-adrenergic receptor agonists. The
      electrophysiological basis of the altered myocardial function was examined in
      left ventricular myocytes isolated from transgenic (G alpha(q)) mice. Action
      potential duration was significantly prolonged in G alpha(q) compared with
      nontransgenic (NTG) myocytes. The densities of inward rectifier K(+) currents,
      transient outward K(+) currents (I(to)), and Na(+)/Ca(2+) exchange currents were
      reduced in G alpha(q) myocytes. Consistent with functional measurements,
      Na(+)/Ca(2+) exchanger gene expression was reduced in G alpha(q) hearts. Kinetics
      or sensitivity of I(to) to 4-aminopyridine was unchanged, but 4-aminopyridine
      prolonged the action potential more in G alpha(q) myocytes. Isoproterenol
      increased L-type Ca(2+) currents (I(Ca)) in both groups, with a similar EC(50),
      but the maximal response in G alpha(q) myocytes was approximately 24% of that in
      NTG myocytes. In NTG myocytes, the maximal increase of I(Ca) with isoproterenol
      or forskolin was similar. In G alpha(q) myocytes, forskolin was more effective
      and enhanced I(Ca) up to approximately 55% of that in NTG myocytes. These results
      indicate that the changes in ionic currents and multiple defects in the beta
      adrenergic receptor/Ca(2+) channel signaling pathway contribute to altered
      ventricular function in this model of cardiac hypertrophy.

PMID- 10899052
TI  - Acute cardiovascular response to isocapnic hypoxia. I. A mathematical model.
AB  - A mathematical model of the acute cardiovascular response to isocapnic hypoxia is
      presented. It includes a pulsating heart, the systemic and pulmonary circulation,
      a separate description of the vascular bed in organs with the higher metabolic
      need, and the local effect of O(2) on these organs. Moreover, the model also
      includes the action of several reflex regulatory mechanisms: the peripheral
      chemoreceptors, the lung stretch receptors, the arterial baroreceptors, and the
      hypoxic response of the central nervous system. All parameters in the model are
      given in accordance with the physiological literature. The simulated overall
      response to a deep hypoxia (28 mmHg) agrees with the experimental data quite
      well, showing a biphasic pattern. The early phase (8-10 s), caused by activation
      of peripheral chemoreceptors, exhibits a moderate increase in mean systemic
      arterial pressure, a decrease in heart rate, a quite constant cardiac output, and
      a redistribution of blood flow to the organs with higher metabolic need at the
      expense of other organs. The later phase (20 s) is characterized by the
      activation of lung stretch receptors and by the central nervous system hypoxic
      response. During this phase, cardiac output and heart rate increase together, and
      blood flow is restored to normal levels also in organs with lower metabolic need.
      The model may be used to gain a deeper understanding of the role of each
      mechanism in the overall cardiovascular response to hypoxia.

PMID- 10899053
TI  - Acute cardiovascular response to isocapnic hypoxia. II. Model validation.
AB  - The role of the different mechanisms involved in the cardiovascular response to
      hypoxia [chemoreceptors, baroreceptors, lung stretch receptors, and central
      nervous system (CNS) hypoxic response] is analyzed in different physiological
      conditions by means of a mathematical model. The results reveal the following: 1)
      The model is able to reproduce the cardiovascular response to hypoxia very well
      between 100 and 28 mmHg PO(2). 2) Sensitivity analysis of the impact of each
      individual mechanism underlines the role of the baroreflex in avoiding excessive
      derangement of systemic arterial pressure and cardiac output during severe
      hypoxia and suggests the existence of significant redundancy among the other
      regulatory factors. 3) Simulation of chronic sinoaortic denervation (i.e.,
      simultaneous exclusion of baroreceptors, chemoreceptors, and lung stretch
      receptors) shows that the CNS hypoxic response alone is able to maintain quite
      normal cardiovascular adjustments to hypoxia; however, suppression of the CNS
      hypoxic response, as might occur during anesthesia, led to a significant arterial
      hypotension. 4) Simulations of experiments with controlled ventilation show a
      significant decrease in heart rate that can only partly be ascribed to
      inactivation of lung stretch receptors. 5) Simulations performed by maintaining
      constant cardiac output suggest that during severe hypoxia the chemoreflex can
      produce a significant decrease in systemic blood volume. In all the previous
      cases, model predictions exhibit a satisfactory agreement with physiological
      data.

PMID- 10899054
TI  - Biochemical mechanism(s) of stunning in conscious dogs.
AB  - The mechanism(s) underlying contractile dysfunction in cardiac stunning is not
      completely understood. The expression and/or the phosphorylation state of cardiac
      Ca(2+) homoeostasis-regulating proteins might be altered in stunning. We tested
      this hypothesis in a well-characterized model of stunning. Conscious dogs were
      chronically instrumented, and the left anterior descending artery (LAD) was
      occluded for 10 min. Thereafter, reperfusion of the LAD was initiated. Tissues
      from reperfused LAD (stunned) and Ramus circumflexus (control) areas were
      obtained when left ventricular regional wall thickening fraction had recovered by
      50%. Northern and Western blotting revealed no differences in the expression of
      the following genes: phospholamban, calsequestrin, sarco(endo)plasmic reticulum
      Ca(2+)-ATPase 2a, and the inhibitory subunit of troponin I (TnI). However, the
      phosphorylation state of TnI and phospholamban were reduced in the LAD area.
      Fittingly, cAMP levels were reduced by 28% (P < 0.05). It is concluded that the
      contractile dysfunction in cardiac stunning might be mediated in part by
      decreased levels of cAMP and subsequently a reduced phosphorylation state of
      phospholamban and TnI.

PMID- 10899055
TI  - Low [Mg(2+)](o) induces contraction of cerebral arteries: roles of tyrosine and
      mitogen-activated protein kinases.
AB  - The present study was designed to investigate the mechanism of action of low
      extracellular magnesium ion concentration ([Mg(2+)](o)) on isolated canine
      basilar arteries and single cerebral vascular smooth muscle cells from these
      arteries. Low-[Mg(2+)](o) medium (0-0.6 mM) produces endothelium-independent
      contractions in isolated canine basilar arteries in a concentration-dependent
      manner; the lower the concentration of [Mg(2+)](o), the stronger the
      contractions. The low-[Mg(2+)](o) medium-induced contractions are significantly
      attenuated by pretreatment of the arteries with low concentrations of either SB
      203580, U-0126, PD-98059, genistein, or an Src homology 2 (SH2) domain inhibitor
      peptide. IC(50) levels obtained for these five antagonists are consistent with
      reported inhibitor constant (K(i)) values for these tyrosine kinase and mitogen
      activated protein kinase (MAPK) antagonists. Low-[Mg(2+)](o) medium (0-0.6 mM)
      produces transient intracellular calcium ion concentration ([Ca(2+)](i)) peaks
      followed by a slow, sustained, and elevated plateau of [Ca(2+)](i) in primary
      single smooth muscle cells from canine basilar arteries. Low-[Mg(2+)](o) medium
      induces rapid and stable increases in [Ca(2+)](i); these increases are inhibited
      markedly in the presence of either SB-203580, U-0126, PD-98059, genistein or a
      SH2 domain inhibitor peptide. Several specific antagonists of known endogenously
      formed vasoconstrictors do not inhibit or attenuate either the low-[Mg(2+)](o)
      induced contractions or the elevation of [Ca(2+)](i). The present study suggests
      that activation of several cellular signaling pathways, such as protein tyrosine
      kinases (including the Src family) and MAPK, appears to play important roles in
      low-[Mg(2+)](o)-induced contractions and the elevation of [Ca(2+)](i) in smooth
      muscle cells from canine basilar arteries.

PMID- 10899056
TI  - Free radicals upregulate complement expression in rabbit isolated heart.
AB  - Both free radicals and complement activation can injure tissue. Our study
      determined whether free radicals alter complement production by the myocardium.
      Isolated hearts from New Zealand White rabbits were perfused on a Langendorff
      apparatus and exposed to xanthine (X; 100 microM) plus xanthine oxidase (XO; 8
      mU/ml) (X/XO). The free radical-generating system significantly (P < 0.05)
      increased C1q and also increased C1r, C3, C8, and C9 transcription compared with
      controls. Immunohistological examination revealed augmented membrane attack
      complex deposition on X/XO-treated tissue. X/XO-treated hearts also exhibited
      significant (P < 0.05) increases in coronary perfusion pressure and left
      ventricular end-diastolic pressure and a decrease in left-ventricular developed
      pressure. N-(2-mercaptopropionyl)-glycine (3 mM), in conjunction with the
      superoxide dismutase mimetic SC-52608 (100 microM), significantly (P < 0.05)
      reduced the upregulation of C1q, C1r, C3, C8, and C9 mRNA expression elicited by
      X/XO. The antioxidants also ameliorated the deterioration in function caused by
      X/XO. Local complement activation may represent a mechanism by which free
      radicals mediate tissue injury.

PMID- 10899057
TI  - Colocalization of dihydropyridine and ryanodine receptors in neonate rabbit heart
      using confocal microscopy.
AB  - Because of undeveloped T tubules and sparse sarcoplasmic reticulum, Ca(2+)
      induced Ca(2+) release (CICR) may not be the major mechanism providing
      contractile Ca(2+) in the neonatal heart. Spatial association of dihydropyridine
      receptors (DHPRs) and ryanodine receptors (RyRs), a key factor for CICR, was
      examined in isolated neonatal rabbit ventricular myocytes aged 3-20 days by
      double-labeling immunofluorescence and confocal microscopy. We found a
      significant increase (P < 0.0005) in the degree of colocalization of DHPR and RyR
      during development. The number of voxels containing DHPR that also contained RyR
      in the 3-day-old group (62 +/- 1.8%) was significantly lower than in the other
      age groups (76 +/- 1.3 in 6-day old, 75 +/- 1.2 in 10-day old, and 79 +/- 0.9% in
      20-day old). The number of voxels containing RyR that also contained DHPR was
      significantly higher in the 20-day-old group (17 +/- 0.5%) compared with the
      other age groups (10 +/- 0.7 in 3-day old, 11 +/- 0.6 in 6-day old, and 11 +/-
      0.5% in 10-day old). During this period, the pattern of colocalization changed
      from mostly peripheral to mostly internal couplings. Our results provide a
      structural basis for the diminished prominence of CICR in neonatal heart.

PMID- 10899058
TI  - Effects of exercise training on LV performance and mortality in a murine model of
      dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DC) is a leading cause of cardiovascular morbidity, and
      nonpharmacological therapies, such as exercise training, have been suggested. The
      effects of exercise on left ventricular (LV) function and mortality remain
      controversial. Using a recently described murine model of DC, which involves a
      dominant-negative form of the cAMP response element binding protein (CREB)
      transcription factor (CREB(A133)) under the control of the cardiac myocyte
      specific alpha-myosin heavy chain promoter, we sought to assess the effects of
      moderate-intensity exercise training on LV performance and mortality. Thirty-two
      transgenic mice were subjected to exercise training and compared with sedentary
      controls. There was progressive enlargement in LV dimensions in both the
      sedentary and exercise-trained mice. LV performance was progressively impaired,
      and exercise training did not prevent this decline. The sedentary CREB(A133) mice
      displayed a significantly increased rate of death, and exercise training did not
      prevent or delay this excess mortality. The CREB(A133) murine model of inherited
      DC demonstrated progressive ventricular dilatation and dysfunction with increased
      mortality, which was not altered with 12 wk of moderate-intensity exercise
      training.

PMID- 10899059
TI  - Maturation of end-systolic stress-strain relations in chick embryonic myocardium.
AB  - The embryonic myocardium increases functional performance geometrically during
      cardiac morphogenesis. We investigated developmental changes in the in vivo end
      systolic stress-strain relations of embryonic chick myocardium in stage 17, 21,
      and 24 white Leghorn chick embryos (n = 10 for each stage). End-systolic stress
      strain relations were linear in all developmental stages. End-systolic strain
      decreased from 0.50 +/- 0.02 to 0.31 +/- 0.01 (mean +/- SE, P < 0.05), while
      average end-systolic wall stress was similar at 3.29 +/- 0.34 to 4.19 +/- 0.43
      mmHg (P = 0.14) from stage 17 to 24. Normalized end-systolic myocardial
      stiffness, a load-independent index of ventricular contractility, increased from
      2.98 +/- 0.19 to 6.03 +/- 0.39 mmHg from stage 17 to 24 (P < 0.05). Zero-stress
      midwall volume increased from 0.024 +/- 0.002 to 0.124 +/- 0.004 microl from
      stage 17 to 24 (P < 0.05). These results suggest that the embryonic ventricle
      increases normalized ventricular "contractility" while maintaining average end
      systolic wall stress over a relatively narrow range during cardiovascular
      morphogenesis.

PMID- 10899060
TI  - Postextrasystolic contractile decay always contains exponential and alternans
      components in canine heart.
AB  - In isolated, blood-perfused canine hearts, postextrasystolic potentiation (PESP)
      decays monotonically after a noncompensatory pause following a spontaneous
      extrasystole (ES). The monotonic PESP decay yields myocardial internal Ca(2+)
      recirculation fraction (RF). We have found that after a compensatory pause (CP),
      PESP decays in alternans, consisting of an exponential and a sinusoidal decay
      component. We have proposed that this exponential component also yields RF. In
      the present study, we examined the reliability of this alternative method by
      widely changing the ES coupling interval (ESI), CP, and heart rate in the canine
      excised, cross-circulated left ventricle. We found that all PESP decays consisted
      of the sum of an exponential and a sinusoidal decay component of variable
      magnitudes whether a CP existed or not. Their decay constants as well as the
      calculated RF were independent of the ESI and CP. This confirmed the utility of
      our alternative RF determination method regardless of the ESI, CP, and heart
      rate. Direct experimental evidence of Ca(2+) dynamics supportive of this
      alternative method, however, remains to be obtained.

PMID- 10899061
TI  - Increases in leptin levels, sympathetic drive, and weight gain in obstructive
      sleep apnea.
AB  - Patients with obstructive sleep apnea (OSA) are frequently obese and are
      predisposed to weight gain. They also have heightened sympathetic drive. We
      reasoned that noradrenergic activation of beta(3)-receptors on adipocytes would
      inhibit leptin production, predisposing to obesity in sleep apnea. We therefore
      tested the hypothesis that obesity and predisposition to weight gain in OSA are
      associated with low levels of plasma leptin. We prospectively studied 32 male
      patients (43 +/- 2 yr) with OSA who were newly diagnosed and never treated and
      who were free of any other diseases. Control measurements were obtained from 32
      similarly obese closely matched male subjects (38 +/- 2 yr). Leptin levels were
      13.7 +/- 1.3 and 9.2 +/- 1.2 ng/ml in patients with OSA and controls,
      respectively (P = 0.02). Weight gain over the year before diagnosis was 5.2 +/-
      1.7 and 0.5 +/- 0.9 kg in sleep apnea patients and similarly obese control
      subjects, respectively (P = 0.04). Muscle sympathetic activity was 46 +/- 4 and
      30 +/- 4 bursts/min in patients with OSA (n = 16) and control subjects (n = 18),
      respectively (P = 0.01). Plasma leptin levels are elevated in newly diagnosed
      otherwise healthy patients with untreated sleep apnea beyond the levels seen in
      similarly obese control subjects without sleep apnea. Higher leptin levels in
      OSA, independent of body fat content, suggest that OSA is associated with
      resistance to the weight-reducing effects of leptin.

PMID- 10899062
TI  - Altered cardiac excitation-contraction coupling in ventricular myocytes from
      spontaneously diabetic BB rats.
AB  - Cardiac excitation-contraction (E-C) coupling abnormalities in chemically induced
      diabetes have been well defined. Heart dysfunction has also been reported in
      diabetes of genetic origin. The purpose of this study was to determine whether
      heart dysfunction in genetically predisposed diabetes is attributable to impaired
      E-C coupling at the cellular level. Myocytes were isolated from 1-yr-old BioBreed
      (BB) spontaneously diabetic-prone (BB/DP) rats and their diabetic-resistant
      littermates (BB/DR). Mechanical properties were evaluated by use of a video edge
      detection system. Myocytes were electrically stimulated at 0.5 Hz. The
      contractile properties analyzed included peak shortening (PS), time-to-peak
      shortening (TPS), time-to-90% relengthening (TR(90)), and maximal velocities of
      shortening and relengthening (+/-dL/dt). Intracellular Ca(2+) handling was
      evaluated with fura 2 fluorescent dye. Myocytes from spontaneously diabetic
      hearts exhibited a depressed PS, prolonged TPS and TR(90), and reduced +/-dL/dt.
      Consistent with the mechanical response, myocytes from the BB/DP group displayed
      reduced resting and peak intracellular Ca(2+) concentration associated with a
      slowed Ca(2+)-transient decay. Furthermore, myocytes from BB/DP hearts were less
      responsive to increases in extracellular Ca(2+) and norepinephrine and equally
      responsive to increases in stimulation frequency and KCl compared with those from
      the BB/DR group. These results suggest that the genetic diabetic state produces
      altered cardiac E-C coupling, in part, because of abnormalities of the myocyte,
      similar to that demonstrable after chemically induced diabetes or during human
      diabetes.

PMID- 10899063
TI  - Isometric handgrip training reduces arterial pressure at rest without changes in
      sympathetic nerve activity.
AB  - The purpose of this study was to determine whether isometric handgrip (IHG)
      training reduces arterial pressure and whether reductions in muscle sympathetic
      nerve activity (MSNA) mediate this drop in arterial pressure. Normotensive
      subjects were assigned to training (n = 9), sham training (n = 7), or control (n
      = 8) groups. The training protocol consisted of four 3-min bouts of IHG exercise
      at 30% of maximal voluntary contraction (MVC) separated by 5-min rest periods.
      Training was performed four times per week for 5 wk. Subjects' resting arterial
      pressure and heart rate were measured three times on 3 consecutive days before
      and after training, with resting MSNA (peroneal nerve) recorded on the third day.
      Additionally, subjects performed IHG exercise at 30% of MVC to fatigue followed
      by muscle ischemia. In the trained group, resting diastolic (67 +/- 1 to 62 +/- 1
      mmHg) and mean arterial pressure (86 +/- 1 to 82 +/- 1 mmHg) significantly
      decreased, whereas systolic arterial pressure (116 +/- 3 to 113 +/- 2 mmHg),
      heart rate (67 +/- 4 to 66 +/- 4 beats/min), and MSNA (14 +/- 2 to 15 +/- 2
      bursts/min) did not significantly change following training. MSNA and
      cardiovascular responses to exercise and postexercise muscle ischemia were
      unchanged by training. There were no significant changes in any variables for the
      sham training and control groups. The results indicate that IHG training is an
      effective nonpharmacological intervention in lowering arterial pressure.

PMID- 10899064
TI  - Electrotonic suppression of early afterdepolarizations in isolated rabbit
      Purkinje myocytes.
AB  - Many studies suggest that early afterdepolarizations (EADs) arising from Purkinje
      fibers initiate triggered arrhythmias under pathological conditions. However,
      electrotonic interactions between Purkinje and ventricular myocytes may either
      facilitate or suppress EAD formation at the Purkinje-ventricular interface. To
      determine conditions that facilitated or suppressed EADs during Purkinje
      ventricular interactions, we coupled single Purkinje myocytes and aggregates
      isolated from rabbit hearts to a passive model cell via an electronic circuit
      with junctional resistance (R(j)). The model cell had input resistance (R(m,v))
      of 50 M Omega, capacitance of 39 pF, and a variable rest potential (V(rest,v)).
      EADs were induced in Purkinje myocytes during superfusion with 1 microM
      isoproterenol. Coupling at high R(j) to normally polarized V(rest,v) established
      a repolarizing coupling current during all phases of the Purkinje action
      potential. This coupling current preferentially suppressed EADs in single cells
      with mean membrane resistance (R(m,p)) of 297 M Omega, whereas EAD suppression in
      larger aggregates with mean R(m,p) of 80 M Omega required larger coupling
      currents. In contrast, coupling to elevated V(rest,v) established a depolarizing
      coupling current during late phase 2, phase 3, and phase 4 that facilitated EAD
      formation and induced spontaneous activity in single Purkinje myocytes and
      aggregates. These results have important implications for arrhythmogenesis in the
      infarcted heart when reduction of the ventricular mass due to scarring alters the
      R(m,p)-to-R(m,v) ratio and in the ischemic heart when injury currents are
      established during coupling between polarized Purkinje myocytes and depolarized
      ventricular myocytes.

PMID- 10899065
TI  - Basic FGF reduces stunning via a NOS2-dependent pathway in coronary-perfused
      mouse hearts.
AB  - Basic fibroblast growth factor (FGF-2) may protect the heart from ischemia
      reperfusion injury (stunning) by stimulating nitric oxide (NO) production. To
      test this hypothesis, we pretreated coronary-perfused mouse hearts with 1
      microg/ml FGF-2 or vehicle control before the onset of ischemia. Intracellular
      calcium (Ca(i)(2+)) was estimated by aequorin, and NO release was measured with
      an NO-selective electrode. Hearts perfused with FGF-2 maintained significantly
      better left ventricular (LV) function during ischemia than hearts perfused with
      vehicle. FGF-2 significantly delayed the onset of ischemic contracture and
      improved LV recovery during reperfusion. Ca(i)(2+) was similar in both groups at
      baseline during ischemia and reperfusion. L-N(6)-(1-iminoethyl)lysine, a
      selective inhibitor of inducible NO synthase (NOS2), obliterated the protective
      effects of FGF-2. In transgenic hearts deficient in the expression of NOS2 (NOS2
      /-), FGF-2 did not attenuate ischemia-induced LV dysfunction. Measurements of NO
      release demonstrated that FGF-2 perfusion significantly increased NO in wild-type
      but not in NOS2-/- hearts. We conclude that basic FGF attenuates myocardial
      stunning independent of alterations in Ca(i)(2+) by stimulating NO production via
      an NOS2-dependent pathway.

PMID- 10899066
TI  - Reinforcement of arteriolar myogenic activity by endogenous ANG II:
      susceptibility to dietary salt.
AB  - The purpose of this study was to determine whether endogenous ANG II augments
      arteriolar myogenic behavior in striated muscle. Because circulating ANG II is
      decreased during high salt intake, we also investigated whether dietary salt
      could alter any influence of ANG II on myogenic behavior. Normotensive rats fed
      low-salt (0.45%, LS) or high-salt (7%, HS) diets were enclosed in a ventilated
      box with the spinotrapezius muscle exteriorized for intravital microscopy.
      Dietary salt did not affect resting arteriolar diameters. Microvascular pressure
      elevation by box pressurization caused greater arteriolar constriction in LS rats
      (up to 12 microm) than in HS rats (up to 4 microm). The ANG II-receptor
      antagonists saralasin and losartan attenuated myogenic responsiveness in LS rats
      but not HS rats. The bradykinin-receptor antagonist HOE-140 had no effect on
      myogenic responsiveness in LS rats but augmented myogenic responsiveness in HS
      rats. HOE-140 with the angiotensin-converting enzyme inhibitor captopril
      attenuated myogenic responsiveness to a greater extent in LS rats than in HS
      rats. We conclude that endogenous ANG II normally reinforces arteriolar myogenic
      behavior in striated muscle and that attenuated myogenic behavior associated with
      high salt intake is due to decreased circulating ANG II and increased local kinin
      levels.

PMID- 10899067
TI  - Microvascular dilation in response to occlusion: a coordinating role for
      conducted vasomotor responses.
AB  - In rat cremasteric microcirculation, mechanical occlusion of one branch of an
      arteriolar bifurcation causes an increase in flow and vasodilation of the
      unoccluded daughter branch. This dilation has been attributed to the operation of
      a shear stress-dependent mechanism in the microcirculation. Instead of or in
      addition to this, we hypothesized that the dilation observed during occlusion is
      the result of a conducted signal originating distal to the occlusion. To test
      this hypothesis, we blocked the ascending spread of conducted vasomotor responses
      by damaging the smooth muscle and endothelial cells in a 200-microm segment of
      second- or third-order arterioles. We found that a conduction blockade eliminated
      or diminished the occlusion-associated increase in flow through the unoccluded
      branch and abolished or strongly attenuated the vasodilatory response in both
      vessels at the branch. We also noted that vasodilations induced by ACh (10(-4) M,
      0.6 s) spread to, but not beyond, the area of damage. Taken together, these data
      provide strong evidence that conducted vasomotor responses have an important role
      in coordinating blood flow in response to an arteriolar occlusion.

PMID- 10899068
TI  - P2X(4) receptors mediate ATP-induced calcium influx in human vascular endothelial
      cells.
AB  - ATP induces Ca(2+) influx across the cell membrane and activates release from
      intracellular Ca(2+) pools in vascular endothelial cells (ECs). Ca(2+) signaling
      leads to the modification of a variety of EC functions, including the production
      of vasoactive substances such as nitric oxide and prostacyclin. However, the
      molecular mechanisms for ATP-induced Ca(2+) influx in ECs have not been
      thoroughly clarified. Here we demonstrate evidence that a P2X(4) receptor for an
      ATP-gated cation channel is predominantly expressed in human ECs and is involved
      in the ATP-induced Ca(2+) influx. Northern blot analysis distinctly showed the
      expression of P2X(4) mRNA in human ECs cultured from the umbilical vein, aorta,
      pulmonary artery, and skin microvessels. Competitive PCR revealed that P2X(4)
      mRNA expression was much higher in ECs than was the expression of other subtypes,
      including P2X(1), P2X(3), P2X(5), and P2X(7). Treatment of ECs with antisense
      oligonucleotides designed to target the P2X(4) receptor decreased the P2X(4) mRNA
      and protein levels to approximately 25% of control levels and markedly prevented
      the ATP-induced Ca(2+) influx.

PMID- 10899069
TI  - Shear stress enhances human endothelial cell wound closure in vitro.
AB  - Repair of the endothelium occurs in the presence of continued blood flow, yet the
      mechanisms by which shear forces affect endothelial wound closure remain elusive.
      Therefore, we tested the hypothesis that shear stress enhances endothelial cell
      wound closure. Human umbilical vein endothelial cells (HUVEC) or human coronary
      artery endothelial cells (HCAEC) were cultured on type I collagen-coated
      coverslips. Cell monolayers were sheared for 18 h in a parallel-plate flow
      chamber at 12 dyn/cm(2) to attain cellular alignment and then wounded by scraping
      with a metal spatula. Subsequently, the monolayers were exposed to a laminar
      shear stress of 3, 12, or 20 dyn/cm(2) under shear-wound-shear (S-W-sH) or shear
      wound-static (S-W-sT) conditions for 6 h. Wound closure was measured as a
      percentage of original wound width. Cell area, centroid-to-centroid distance, and
      cell velocity were also measured. HUVEC wounds in the S-W-sH group exposed to 3,
      12, or 20 dyn/cm(2) closed to 21, 39, or 50%, respectively, compared with only
      59% in the S-W-sT cells. Similarly, HCAEC wounds closed to 29, 49, or 33% (S-W
      sH) compared with 58% in the S-W-sT cells. Cell spreading and migration, but not
      proliferation, were the major mechanisms accounting for the increases in wound
      closure rate. These results suggest that physiological levels of shear stress
      enhance endothelial repair.

PMID- 10899070
TI  - Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung
      injury.
AB  - Apocynin (4-hydroxy-3-methoxy-acetophenone) inhibits NADPH oxidase in activated
      polymorphonuclear (PMN) leukocytes, preventing the generation of reactive oxygen
      species. To determine if apocynin attenuates ischemia-reperfusion lung injury, we
      examined the effects of apocynin (0.03, 0.3, and 3 mM) in isolated in situ sheep
      lungs. In diluent-treated lungs, reperfusion with blood (180 min) after 30 min of
      ischemia (ventilation 28% O(2), 5% CO(2)) caused leukocyte sequestration in the
      lung and increased vascular permeability [reflection coefficient for albumin
      (sigma(alb)) 0.47 +/- 0.10, filtration coefficient (K(f)) 0.14 +/- 0.03 g. min(
      1). mmHg(-1). 100 g(-1)] compared with nonreperfused lungs (sigma(alb) 0.77 +/-
      0. 03, K(f) 0.03 +/- 0.01 g. min(-1). mmHg(-1). 100 g(-1); P < 0.05). Apocynin
      attenuated the increased protein permeability at 0.3 and 3 mM (sigma(alb) 0.69 +/
      0.05 and 0.91 +/- 0.03, respectively, P < 0. 05); K(f) was decreased by 3 mM
      apocynin (0.05 +/- 0.01 g. min(-1). mmHg(-1). 100 g(-1), P < 0.05).
      Diphenyleneiodonium (DPI, 5 microM), a structurally unrelated inhibitor of NADPH
      oxidase, worsened injury (K(f) 0.32 +/- 0.07 g. min(-1). mmHg(-1). 100 g(-1), P <
      0.05). Neither apocynin nor DPI affected leukocyte sequestration. Apocynin and
      DPI inhibited whole blood chemiluminescence and isolated PMN leukocyte-induced
      resazurin reduction, confirming NADPH oxidase inhibition. Apocynin inhibited
      pulmonary artery hypertension and perfusate concentrations of cyclooxygenase
      metabolites, including thromboxane B(2). The cyclooxygenase inhibitor
      indomethacin had no effect on the increased vascular permeability, suggesting
      that cyclooxygenase inhibition was not the explanation for the apocynin results.
      Apocynin prevented ischemia-reperfusion lung injury, but the mechanism of
      protection remains unclear.

PMID- 10899072
TI  - Calcium-activated potassium channels and nitric oxide coregulate estrogen-induced
      vasodilation.
AB  - Nitric oxide synthase (NOS) contributes to estradiol-17beta (E(2)beta)-induced
      uterine vasodilation, but additional mechanisms are involved, and the cellular
      pathways remain unclear. We determined if 1) uterine artery myocytes express
      potassium channels, 2) E(2)beta activates these channels, and 3) channel blockade
      plus NOS inhibition alters E(2)beta-induced uterine vasodilation. Studies of cell
      attached patches identified a 107 +/- 7 pS calcium-dependent potassium channel
      (BK(Ca)) in uterine artery myocytes that rapidly increased single-channel open
      probability 70-fold (P < 0.05) after exposure to 100 nM E(2)beta through an
      apparent cGMP-dependent mechanism. In ovariectomized nonpregnant ewes (n = 11)
      with uterine artery flow probes and catheters, local BK(Ca) blockade with
      tetraethylammonium (TEA; 0.05-0.6 mM) dose dependently inhibited E(2)beta-induced
      uterine vasodilation (n = 37, R = 0.77, P < 0.0001), with maximum inhibition
      averaging 67 +/- 11%. Mean arterial pressure (MAP) and E(2)beta-induced increases
      (P </= 0.001) in heart rate (13%) and contralateral uterine blood flow (UBF,
      approximately 5-fold) were unaffected. Local NOS inhibition plus BK(Ca) blockade,
      using submaximal doses of nitro-L-arginine methyl ester (5 mg/ml) and TEA (0.3
      mM), did not alter basal UBF but completely inhibited ipsilateral E(2)beta
      induced uterine vasodilation without affecting MAP and E(2)beta-induced increases
      in contralateral UBF and heart rate. Acute E(2)beta-mediated uterine vasodilation
      involves rapid activation of uterine artery BK(Ca) and NOS, and the pathway for
      their interaction appears to include activation of guanylyl cyclase.

PMID- 10899071
TI  - Preservation of glucose metabolism in hypertrophic GLUT4-null hearts.
AB  - GLUT4-null mice lacking the insulin-sensitive glucose transporter are not
      diabetic but do exhibit abnormalities in glucose and lipid metabolism. The most
      striking morphological consequence of ablating GLUT4 is cardiac hypertrophy.
      GLUT4-null hearts display characteristics of hypertrophy caused by hypertension.
      However, GLUT4-null mice have normal blood pressure and maintain a normal cardiac
      contractile protein profile. Unexpectedly, although they lack the predominant
      glucose transporter in the heart, GLUT4-null hearts transport glucose and
      synthesize glycogen at normal levels, but gene expression of rate-limiting
      enzymes involved in fatty acid oxidation is decreased. The GLUT4-null heart
      represents a unique model of hypertrophy that may be used to study the
      consequences of altered substrate utilization in normal and pathophysiological
      conditions.

PMID- 10899073
TI  - Mechanism of decreased adenosine protection in reperfusion injury of aging rats.
AB  - The purpose of this study was to determine whether the protective effects of
      adenosine on myocardial ischemia-reperfusion injury are altered with age, and if
      so, to clarify the mechanisms that underlie this change related to nitric oxide
      (NO) derived from the vascular endothelium. Isolated perfused rat hearts were
      exposed to 30 min of ischemia and 60 min of reperfusion. In the adult hearts,
      administration of adenosine (5 micromol/l) stimulated NO release (1. 06 +/- 0.19
      nmol. min(-1). g(-1), P < 0.01 vs. vehicle), increased coronary flow, improved
      cardiac functional recovery (left ventricular developed pressure 79 +/- 3.8 vs.
      57 +/- 3.1 mmHg in vehicle, P < 0.001; maximal rate of left ventricular pressure
      development 2,385 +/- 103 vs. 1,780 +/- 96 in vehicle, P < 0.001), and reduced
      myocardial creatine kinase loss (95 +/- 3.9 vs. 159 +/- 4.6 U/100 mg protein, P <
      0.01). In aged hearts, adenosine-stimulated NO release was markedly reduced
      (+0.42 +/- 0.12 nmol. min(-1). g(-1) vs. vehicle), and the cardioprotective
      effects of adenosine were also attenuated. Inhibition of NO production in the
      adult hearts significantly decreased the cardioprotective effects of adenosine,
      whereas supplementation of NO in the aged hearts significantly enhanced the
      cardioprotective effects of adenosine. The results show that the protective
      effects of adenosine on myocardial ischemia-reperfusion injury are markedly
      diminished in aged animals, and that the loss in NO release in response to
      adenosine may be at least partially responsible for this age-related alteration.

PMID- 10899075
TI  - Sodium-potassium-ATPase electrogenicity in cerebral precapillary arterioles.
AB  - Electrogenicity of the Na(+)/K(+) pump has the capability to generate a large
      negative membrane potential independently of ion-channel current. The high
      background membrane resistance of arterioles may make them susceptible to such an
      effect. Pump current was detected by patch-clamp recording from smooth muscle
      cells in fragments of arterioles (diameter 24-58 microm) isolated from pial
      membrane of rabbit cerebral cortex. The current was 20 pA at -60 mV, and the
      extrapolated zero current potential was -160 mV. Two methods of estimating the
      effect of pump electrogenicity on resting potential indicated an average
      contribution of -35 mV. In 20% of the recordings, block of inward rectifier K(+)
      channels by 10-100 microM Ba(2+) led to a small depolarization, but
      hyperpolarization was a more common response. Ba(2+) also inhibited
      depolarization evoked by 20 mM K(+). In arterioles within intact pial membrane,
      Ba(2+) failed to evoke constriction but inhibited K(+)-induced constriction. The
      data suggest that cerebral arterioles are vulnerable to the hyperpolarizing
      effect of the Na(+)/K(+) pump, excessive effects of which are prevented by
      depolarizing inward rectifier K(+) current

PMID- 10899074
TI  - Role of cGMP versus 20-HETE in the vasodilator response to nitric oxide in rat
      cerebral arteries.
AB  - This study examined the response to nitric oxide (NO) in rat middle cerebral
      arteries (MCA). NO donors increased the activity of a 205-pS K(+) channel
      recorded from vascular smooth muscle (VSM) cells isolated from MCA 10-fold.
      Blockade of guanylyl cyclase activity with 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin
      1-one (ODQ, 10(-5) M) did not alter the effect of NO on this channel. In
      contrast, adding 20-hydroxyeicosatetraenoic acid (20-HETE) to the bath (10(-7) M)
      abolished the response to NO. NO donors also increased the diameter of serotonin
      preconstricted MCA to 85% of control. Blockade of K(+) channels with iberiotoxin
      or a high-K(+) medium reduced this response by 50%. ODQ (10(-5) M) reduced this
      response by 47 +/- 3%, whereas preventing the fall of 20-HETE levels reduced the
      response by 59 +/- 2% (n = 5). Blockade of both pathways eliminated the response
      to NO donors. These results indicate that activation of K(+) channels contributes
      50% to vasodilator response to NO in rat MCA. This is mediated by a fall in 20
      HETE levels rather than a rise in cGMP levels or a direct effect of NO.

PMID- 10899076
TI  - Substrate-dependent proton load and recovery of stunned hearts during pyruvate
      dehydrogenase stimulation.
AB  - Stimulation of pyruvate dehydrogenase (PDH) improves functional recovery of
      postischemic hearts. This study examined the potential for a mechanism mediated
      by substrate-dependent proton production and intracellular pH. After 20 min of
      ischemia, isolated rabbit hearts were reperfused with or without 5 mM
      dichloroacetate (DCA) in the presence of either 5 mM glucose, 5 mM glucose + 2.5
      mM lactate, or 5 mM glucose + 2.5 mM pyruvate. DCA inhibits PDH kinase,
      increasing the proportion of dephosphorylated, active PDH. Unlike pyruvate or
      glucose alone, lactate + glucose did not support the effects of DCA on the
      recovery of rate-pressure product (RPP) (without DCA, RPP = 14,000 +/- 1,200, n =
      6; with DCA, RPP = 13,700 +/- 1,800, n = 9). Intracellular pH, from (31)P nuclear
      magnetic resonance spectra, returned to normal within 2.1 min of reperfusion with
      all substrates except for lactate + glucose + DCA or lactate + DCA, which delayed
      pH recovery for up to 12 min (at 2.1 min pH = 6. 00 +/- 0.08, lactate + glucose +
      DCA; pH = 6.27 +/- 0.34, for lactate + DCA). Hearts were also reperfused after 10
      min of ischemia with 0.5 mM palmitate + 5 mM DCA and either 2.5 mM pyruvate or
      2.5 mM lactate. Again, intracellular pH recovery was delayed in the presence of
      lactate. PDH activation in the presence of lactate also decreased coupling of
      oxidative metabolism to mechanical work. These findings have implications for
      therapeutic use of stimulated carbohydrate oxidation in stunned hearts.

PMID- 10899077
TI  - AGT M235T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE
      Family Study.
AB  - We investigated the association between angiotensinogen (AGT) and angiotensin
      converting enzyme (ACE) gene polymorphisms and exercise training responses of
      resting and exercise blood pressure (BP). BP at rest and during submaximal (50
      watts) and maximal exercise tests was measured before and after 20 wk of
      endurance training in 476 sedentary normotensive Caucasian subjects from 99
      families. AGT M235T and ACE insertion/deletion polymorphisms were typed with PCR
      based methods. Men carrying the AGT MM and MT genotypes showed 3. 7 +/- 0.6 and
      3.2 +/- 0.5 (SE) mmHg reductions, respectively, in diastolic BP at 50 watts
      (DBP(50)), whereas, in the TT homozygotes, the decrease was 0.4 +/- 1.0 mmHg (P =
      0.016 for trend, adjusted for age, body mass index, and baseline DBP(50)). Men
      with the ACE DD genotype showed a slightly greater decrease in DBP(50) (4.4 +/-
      0.6 mmHg) than the II and ID genotypes (2.8 +/- 0.7 and 2.4 +/- 0.5 mmHg,
      respectively, P = 0.050). Furthermore, a significant (P = 0.022) interaction
      effect between the AGT and ACE genes was noted for DBP(50); the AGT TT
      homozygotes carrying the ACE D allele showed no response to training. Men with
      the AGT TT genotype had greater (P = 0.007) diastolic BP (DBP) response to acute
      maximal exercise at baseline. However, the difference disappeared after the
      training period. No associations were found in women. These data suggest that, in
      men, the genetic variation in the AGT locus modifies the responsiveness of
      submaximal exercise DBP to endurance training, and interactions between the AGT
      and ACE loci can alter this response.

PMID- 10899078
TI  - Regulation of myocardial [(13)C]glucose metabolism in conscious rats.
AB  - Administration of supplemental glucose and/or insulin is postulated to improve
      the outcome from myocardial ischemia by increasing the heart's relative
      utilization of glucose as an energy substrate. To examine the degree to which
      circulating glucose and insulin levels actually influence myocardial substrate
      preference in vivo, we infused conscious, chronically catheterized rats with D-[1
      (13)C]glucose and compared steady-state (13)C enrichment of plasma glucose with
      that of myocardial glycolytic ([3-(13)C]alanine) and oxidative ([4
      (13)C]glutamate) intermediary metabolites. In fasting rats, [3-(13)C]alanine-to
      [1-(13)C]glucose and [4-(13)C]glutamate-to-[3-(13)C]alanine ratios averaged 0.16
      +/- 0.12 and 0.14 +/- 0.03, respectively, indicating that circulating glucose
      contributed 32% of myocardial glycolytic flux, whereas subsequent flux through
      pyruvate dehydrogenase contributed 14% of total tricarboxylic acid (TCA) cycle
      activity. Raising plasma glucose to 11 mmol/l, or insulin to 500 pmol/l,
      increased these contributions equivalently. At supraphysiological (>6,500 pmol/l)
      insulin levels, the plasma glucose contribution to glycolysis increased further,
      and addition of hyperglycemia made it the sole glycolytic substrate, yet [4
      (13)C]glutamate-to-[3-(13)C]alanine ratios remained </=0.60. Thus plasma levels
      of glucose and insulin independently regulate the proportional contribution of
      exogenous glucose to myocardial glycolytic and TCA cycle flux in vivo in a dose
      dependent manner. However, even at supraphysiological levels, nonglucose
      substrates continue to supply >/=40% of myocardial TCA cycle flux.

PMID- 10899079
TI  - Retinoic acid upregulates beta(1)-integrin in vascular smooth muscle cells and
      alters adhesion to fibronectin.
AB  - Retinoic acid has an established physiological role in differentiation,
      development, and cellular growth. This study investigated the action of all-trans
      retinoic acid (ATRA) on vascular integrins, cell-surface receptors that control
      growth and remodeling of blood vessels. The beta(1)-integrin subunit mRNA and
      protein was induced after treatment with ATRA in two different rat vascular
      smooth muscle cell lines. To relate this result to the in vivo state, the aortas
      from adult rats fed with therapeutic doses of ATRA were examined for beta(1)
      integrin protein. A significant upregulation of the integrin subunit was observed
      in vivo. To assess if this increase contributed to physiological changes in
      cellular function, cells treated with ATRA were tested for alterations in
      adhesion to extracellular matrix proteins. The cells exposed to the retinoid were
      seen to adhere more strongly to fibronectin, via the beta(1)-integrin. These
      results showed that modulation of vascular integrins by ATRA in adult rats
      contributes to functional changes that can cause remodeling of blood vessels.

PMID- 10899080
TI  - Effects of cardiotrophin-1 on hemodynamics and endocrine function of the heart.
AB  - Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily of cytokines,
      possesses hypertrophic actions and atrial natriuretic peptide (ANP)-producing
      activity in vitro. The goal of our study is to elucidate whether CT-1 affects the
      cardiovascular system in vivo. Intravenous injection of CT-1 (4-100 microg/kg) in
      conscious rats evoked significant declines in blood pressure and reflex increases
      in heart rate (HR) in a dose-dependent manner. CT-1 induced no significant change
      in cardiac output (from 260.7 +/- 11.0 to 264.7 +/- 26.6 ml. min(-1). kg(-1), P =
      not significant), which was compatible with the results from isolated perfused
      rat hearts; HR, change in pressure over time, left ventricular developed
      pressure, and perfusion pressure were unaffected. Northern blot and RT-PCR
      analyses revealed that CT-1 increased expression of inducible nitric oxide
      synthase (iNOS) in lung and aorta but not in heart or liver. Pretreatment with
      aminoguanidine, a specific iNOS inhibitor, inhibited both iNOS mRNA production
      and the depressor effect of CT-1. Interestingly, CT-1 increased ventricular
      expression of ANP and brain natriuretic peptide (BNP). The data demonstrate that
      CT-1 elicits its hypotensive effect via a nitric oxide-dependent mechanism and
      that CT-1 induces ANP and BNP mRNA expression in vivo.

PMID- 10899081
TI  - Mathematical models of action potentials in the periphery and center of the
      rabbit sinoatrial node.
AB  - Mathematical models of the action potential in the periphery and center of the
      rabbit sinoatrial (SA) node have been developed on the basis of published
      experimental data. Simulated action potentials are consistent with those recorded
      experimentally: the model-generated peripheral action potential has a more
      negative takeoff potential, faster upstroke, more positive peak value, prominent
      phase 1 repolarization, greater amplitude, shorter duration, and more negative
      maximum diastolic potential than the model-generated central action potential. In
      addition, the model peripheral cell shows faster pacemaking. The models behave
      qualitatively the same as tissue from the periphery and center of the SA node in
      response to block of tetrodotoxin-sensitive Na(+) current, L- and T-type Ca(2+)
      currents, 4-aminopyridine-sensitive transient outward current, rapid and slow
      delayed rectifying K(+) currents, and hyperpolarization-activated current. A one
      dimensional model of a string of SA node tissue, incorporating regional
      heterogeneity, coupled to a string of atrial tissue has been constructed to
      simulate the behavior of the intact SA node. In the one-dimensional model, the
      spontaneous action potential initiated in the center propagates to the periphery
      at approximately 0.06 m/s and then into the atrial muscle at 0.62 m/s.

PMID- 10899082
TI  - Progressive left ventricular remodeling and apoptosis late after myocardial
      infarction in mouse heart.
AB  - We tested the hypothesis that left ventricular (LV) remodeling late after
      myocardial infarction (MI) is associated with myocyte apoptosis in myocardium
      remote from the infarcted area and is related temporally to LV dilation and
      contractile dysfunction. One, four, and six months after MI caused by coronary
      artery ligation, LV volume and contractile function were determined using an
      isovolumic balloon-in-LV Langendorff technique. Apoptosis and nuclear morphology
      were determined by terminal deoxynucleotidyl transferase-mediated nick end
      labeling (TUNEL) and Hoechst 33258 staining. Progressive LV dilation 1-6 mo post
      MI was associated with reduced peak LV developed pressure (LVDP). In myocardium
      remote from the infarct, there was increased wall thickness and expression of
      atrial natriuretic peptide mRNA consistent with reactive hypertrophy. There was a
      progressive increase in the number of TUNEL-positive myocytes from 1 to 6 mo post
      MI (2.9-fold increase at 6 mo; P < 0. 001 vs. sham). Thus LV remodeling late post
      MI is associated with increased apoptosis in myocardium remote from the area of
      ischemic injury. The frequency of apoptosis is related to the severity of LV
      dysfunction.

PMID- 10899083
TI  - Culture and adenoviral infection of adult mouse cardiac myocytes: methods for
      cellular genetic physiology.
AB  - Rapid development of transgenic and gene-targeted mice and acute genetic
      manipulation via gene transfer vector systems have provided powerful tools for
      cardiovascular research. To facilitate the phenotyping of genetically engineered
      murine models at the cellular and subcellular levels and to implement acute gene
      transfer techniques in single mouse cardiomyocytes, we have modified and improved
      current enzymatic methods to isolate a high yield of high-quality adult mouse
      myocytes (5.3 +/- 0.5 x 10(5) cells/left ventricle, 83.8 +/- 2.5% rod shaped). We
      have also developed a technique to culture these isolated myocytes while
      maintaining their morphological integrity for 2-3 days. The high percentage of
      viable myocytes after 1 day in culture (72.5 +/- 2.3%) permitted both
      physiological and biochemical characterization. The major functional aspects of
      these cells, including excitation-contraction coupling and receptor-mediated
      signaling, remained intact, but the contraction kinetics were significantly
      slowed. Furthermore, gene delivery via recombinant adenoviral infection was
      highly efficient and reproducible. In adult beta(1)/beta(2)-adrenergic receptor
      (AR) double-knockout mouse myocytes, adenovirus-directed expression of either
      beta(1)- or beta(2)-AR, which occurred in 100% of cells, rescued the functional
      response to beta-AR agonist stimulation. These techniques will permit novel
      experimental settings for cellular genetic physiology.

PMID- 10899084
TI  - Construction of a very high-density extracellular electrode array.
AB  - Cellular activation mapping (specifying in time and space the electrical
      activation sequence of cells) is a well-established basic research tool in
      cardiac, neural, and gastric physiology. Much recent research in cardiac mapping
      has focused on large arrays (>200 electrodes) with small electrodes (<500
      microm). Construction of such arrays using standard techniques is tedious and
      yields irregular electrode spacing. We present a novel construction technique
      that rapidly produces large arrays with regularly spaced small electrodes. For
      methods, fine-pitch copper ribbon cables, insulated with either polyvinylchloride
      (PVC) or polyimide (flexible printed circuit; FPC), were assembled together such
      that the active surface was the cut end of the cable. The cut end was sanded and
      polished, then coated with silver and sometimes silver chloride. Once completed,
      the alternating current (AC) root-mean-square (rms) potential was measured
      between two adjacent, individual electrodes. Polarization testing was conducted
      according to a previously reported protocol (Witkowski FX and Penkoske PA. J
      Electrocardiol 21: 273-282, 1988). Activation mapping was conducted in the open
      chest guinea pig with both pacing- and defibrillation- strength stimuli. In terms
      of results, four PVC and three FPC arrays were constructed, ranging from 4 to 400
      electrodes. Two hours of labor were needed to create a complete electrode array,
      independent of the number of electrodes, including connectors and silver/silver
      chloride coating. As expected, the addition of a silver/silver chloride coating
      significantly reduced (0.76-0.42 mV, P < 0.001) the AC rms potential difference
      between two electrodes. A nearly immediate recovery of the potential difference
      between adjacent pairs of silver/silver chloride electrodes was observed after
      defibrillation stimuli.

PMID- 10899085
TI  - Estimation of parallel conductance by dual-frequency conductance catheter in
      mice.
AB  - The conductance catheter method has substantially enhanced the characterization
      of in vivo cardiovascular function in mice. Absolute volume determination
      requires assessment of parallel conductance (V(p)) offset because of conductivity
      of structures external to the blood pool. Although such a determination is
      achievable by hypertonic saline bolus injection, this method poses potential
      risks to mice because of volume loading and/or contractility changes. We tested
      another method based on differences between blood and muscle conductances at
      various catheter excitation frequencies (20 vs. 2 kHz) in 33 open-chest mice. The
      ratio of mean frequency-dependent signal difference to V(p) derived by hypertonic
      saline injection was consistent [0.095 +/- 0.01 (SD), n = 11], and both methods
      were strongly correlated (r(2) = 0.97, P < 0.0001). This correlation persisted
      when the ratio was prospectively applied to a separate group of animals (n = 12),
      with a combined regression relation of V(p(DF)) = 1.1 * V(p(Sal)) - 2.5 [where
      V(p(DF)) is V(p) derived by the dual-frequency method and V(p(Sal)) is V(p)
      derived by hypertonic saline bolus injection], r(2) = 0.95, standard error of the
      estimate = 1.1 microl, and mean difference = 0.6 +/- 1.4 microl. Varying
      V(p(Sal)) in a given animal resulted in parallel changes in V(p(DF)) (multiple
      regression r(2) = 0.92, P < 0.00001). The dominant source of V(p) in mice was
      found to be the left ventricular wall itself, since surrounding the heart in the
      chest with physiological saline or markedly varying right ventricular volumes had
      a minimal effect on the left ventricular volume signal. On the basis of V(p) and
      flow probe-derived cardiac output, end-diastolic volume and ejection fraction in
      normal mice were 28 +/- 3 microl and 81 +/- 6%, respectively, at a heart rate of
      622 +/- 28 min(-1). Thus the dual-frequency method and independent flow signal
      can be used to provide absolute volumes in mice.

PMID- 10899086
TI  - Nitric oxide, an important regulator of perfusion-contraction matching in
      conscious pigs.
AB  - We examined whether nitric oxide (NO) inhibition during moderate reduction in
      coronary blood flow (CBF) would affect perfusion-contraction matching. Coronary
      stenosis (CS) was induced in conscious pigs, which resulted in a stable 39 +/- 1%
      reduction in CBF for 1.5 h. Ischemic zone wall thickening (IZWT) decreased by an
      average of 56 +/- 2% during CS from 2.7 +/- 0.2 mm. After reperfusion, myocardial
      stunning was observed, but this recovered without evidence of necrosis. After
      recovery and subsequent administration of systemic NO synthase inhibition
      (N(omega)-nitro-L-arginine, 25 mg. kg(-1). day(-1) x 3 days), CS for 1.5 h
      reduced CBF similarly but decreased IZWT significantly more, P < 0.05, by 89 +/-
      5%. Myocardial stunning, i.e., the decrease in IZWT at 12 h post-CS, was more
      severe (-65 +/- 5% vs. -21 +/- 3%), P < 0.05. Furthermore, CS during NO synthase
      inhibition resulted in multifocal subendocardial areas of necrosis in the area at
      risk. These data suggest that in the intact, conscious pig, NO inhibition
      prevents perfusion-contraction matching, resulting in intensification of post
      ischemic stunning and development of subendocardial necrosis.

PMID- 10899087
TI  - Trastuzumab in the treatment of metastatic breast cancer : anticancer therapy
      versus cardiotoxicity.
AB  - Trastuzumab, a monoclonal antibody against the HER2 receptor, was recently
      approved for the treatment of metastatic breast cancer. However, 28% of patients
      receiving both an anthracycline and trastuzumab developed heart failure. Although
      HER2 overexpression has been associated with the development of cancer, HER2
      receptors seem to be cardioprotective because they mediate the activation of
      important cardiac survival pathways. Because the morbidity and mortality of heart
      failure surpasses that of many cancers, prudent medical practice mandates that
      physicians learn more about the mechanisms of trastuzumab-induced cardiotoxicity
      and develop algorithms for assessing risk/benefit ratios before extending the use
      of this agent to patients with less invasive forms of breast cancer.

PMID- 10899088
TI  - Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid
      component of the delayed rectifier potassium current.
AB  - BACKGROUND-Several cases of unexpected death have been reported with sildenafil
      in patients predisposed to ischemic cardiac events. Although acute episodes of
      ischemia could account for some of these deaths, we hypothesized that sildenafil
      may have unsuspected electrophysiological effects predisposing some patients to
      proarrhythmia. METHODS AND RESULTS-Studies were undertaken in 10 isolated guinea
      pig hearts that demonstrated prolongation of cardiac repolarization in a reverse
      use-dependent manner by sildenafil 30 mcmol/L. Action potential duration
      increased 15% from baseline 117+/-3 to 134+/-2 ms with sildenafil during pacing
      at 250 ms cycle length, whereas a 6% increase from 99+/-2 to 105+/-2 ms was seen
      with pacing at 150 ms cycle length. Experiments in human ether-a-go-go-related
      gene (HERG)-transfected HEK293 cells (n=30) demonstrated concentration-dependent
      block of the rapid component (I(Kr)) of the delayed rectifier potassium current:
      activating current was 50% decreased at 100 mcmol/L. This effect was confirmed
      using HERG-transfected Chinese hamster ovary (CHO) cells, which exhibit no
      endogenous I(K)-like current. CONCLUSIONS-Sildenafil possesses direct cardiac
      electrophysiological effects similar to class III antiarrhythmic drugs. These
      effects are observed at concentrations that may be found in conditions of
      impaired drug elimination such as renal or hepatic insufficiency, during
      coadministration of another CYP3A substrate/inhibitor, or after drug overdose and
      offer a new potential explanation for sudden death during sildenafil treatment.

PMID- 10899089
TI  - Clinical significance of abnormal electrocardiographic patterns in trained
      athletes.
AB  - BACKGROUND-The prevalence, clinical significance, and determinants of abnormal
      ECG patterns in trained athletes remain largely unresolved. METHODS AND RESULTS
      We compared ECG patterns with cardiac morphology (as assessed by
      echocardiography) in 1005 consecutive athletes (aged 24+/-6 years; 75% male) who
      were participating in 38 sporting disciplines. ECG patterns were distinctly
      abnormal in 145 athletes (14%), mildly abnormal in 257 (26%), and normal or with
      minor alterations in 603 (60%). Structural cardiovascular abnormalities were
      identified in only 53 athletes (5%). Larger cardiac dimensions were associated
      with abnormal ECG patterns: left ventricular end-diastolic cavity dimensions were
      56. 0+/-5.6, 55.4+/-5.7, and 53.7+/-5.7 mm (P<0.001) and maximum wall thicknesses
      were 10.1+/-1.4, 9.8+/-1.3, and 9.3+/-1.4 mm (P<0.001) in distinctly abnormal,
      mildly abnormal, and normal ECGs, respectively. Abnormal ECGs were also most
      associated with male sex, younger age (<20 years), and endurance sports (cycling,
      rowing/canoeing, and cross-country skiing). A subset of athletes (5% of the 1005)
      showed particularly abnormal or bizarre ECG patterns, but no evidence of
      structural cardiovascular abnormalities or an increase in cardiac dimensions.
      CONCLUSIONS-Most athletes (60%) in this large cohort had ECGs that were
      completely normal or showed only minor alterations. A variety of abnormal ECG
      patterns occurred in 40%; this was usually indicative of physiological cardiac
      remodeling. A small but important subgroup of athletes without cardiac
      morphological changes showed striking ECG abnormalities that suggested
      cardiovascular disease; however, these changes were likely an innocent
      consequence of long-term, intense athletic training and, therefore, another
      component of athlete heart syndrome. Such false-positive ECGs represent a
      potential limitation to routine ECG testing as part of preparticipation
      screening.

PMID- 10899090
TI  - Dose and time effects of caffeine intake on human platelet adenosine A(2A)
      receptors : functional and biochemical aspects.
AB  - BACKGROUND-We determined whether repeated caffeine administration at different
      dosages and for different periods of time (400 or 600 mg/d for 1 week or 400 mg/d
      for 2 weeks) upregulates human platelet adenosine A(2A) receptors and is
      accompanied by increases in cAMP accumulation and decreases in aggregation and
      calcium levels after stimulation of A(2A) receptors by the selective agonist 2
      hexynyl-5'-N-ethylcarboxamidoadenosine (HE-NECA). METHODS AND RESULTS-Platelets
      were obtained from peripheral venous blood of 45 healthy human volunteers at the
      end of 2 weeks of caffeine abstinence and at 12, 60, and 108 hours after the last
      dose of caffeine. The lowest dose of caffeine, when given for only 7 days, had no
      effect. Increasing the total dose, either by giving 400 mg/d for 14 days or
      giving 600 mg/d, resulted in binding assays performed with the adenosine A(2A)
      receptor radioligand [(3)H]SCH 58261 [5-amino-7(phenylethyl)-2-(2-furyl)
      pyrazolo[4,3-e]-1,2,4-triazolo[1, 5-c]pyrimidine], in the upregulation of A(2A)
      receptors. Moreover, the potency of HE-NECA to produce antiaggregatory effects, a
      rise in cAMP accumulation, and a decrease in calcium levels was significantly
      increased. CONCLUSIONS-Chronic caffeine intake can lead to upregulation of
      adenosine A(2A) receptors, which is accompanied by sensitization, in a time- and
      dose-dependent manner, to the actions of the agonist HE-NECA.

PMID- 10899091
TI  - Elevation of prostate-specific markers after cardiopulmonary resuscitation.
AB  - BACKGROUND-Prostate-specific antigen (PSA), acid phosphatase (AP), and prostatic
      acid phosphatase (PAP) are serum markers for adenocarcinoma of the prostate
      gland. Previous studies indicated that prostatic ischemia may also produce
      elevations of PSA. Cardiopulmonary resuscitation (CPR) is frequently associated
      with profound tissue hypoperfusion. The present study investigated whether PSA,
      AP, and PAP are influenced by prolonged CPR. METHODS AND RESULTS-PSA, AP, and PAP
      were assessed immediately, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days
      after prolonged CPR (>5 minutes) in 14 male and 5 female patients. No changes
      were noted in women. In men, serum levels increased significantly after CPR and
      gradually decreased to near baseline values after 7 days. PSA, AP, and PAP values
      above the normal range were observed in 63%, 71%, and 64% of all patients,
      respectively. Compared with survivors, nonsurvivors exhibited higher peak serum
      levels of PSA (98.6+/-14.3 versus 1.1+/-2.2 mcg/L; P<0.03), AP (57.0+/-71 versus
      8.6+/-8.8 U/L; P<0.05), and PAP (47.0+/-62 versus 5.7+/-8.0 U/L; P=NS). Patients
      with poor neurological outcome exhibited higher peak serum levels of PSA (86.4+/
      135.5 versus 12.0+/-23.8 mcg/L; P<0.05), AP (50.9+/-68.1 versus 8.7+/-9.6 U/L;
      P=NS), and PAP (41.6+/-59.5 versus 5.8+/-8.8 U/L; P=NS) than patients with good
      neurological outcome. CONCLUSIONS-Prolonged CPR is frequently associated with
      increases of PSA, AP, and PAP serum levels. Therefore, PSA cannot be used for
      diagnosis of adenocarcinoma of the prostate during the first weeks after CPR.
      Further evaluation of these parameters as additional prognostic markers after CPR
      is warranted.

PMID- 10899092
TI  - Dual-chamber pacing in the treatment of neurally mediated tilt-positive
      cardioinhibitory syncope : pacemaker versus no therapy: a multicenter randomized
      study. The Vasovagal Syncope International Study (VASIS) Investigators.
AB  - BACKGROUND-This study was performed to compare implantation of a DDI pacemaker
      with rate hysteresis with no implant in respect to syncopal recurrences in
      patients with severe cardioinhibitory tilt-positive neurally mediated syncope.
      METHODS AND RESULTS-Forty-two patients from 18 European centers were randomized
      to receive a DDI pacemaker programmed to 80 bpm with hysteresis of 45 bpm (19
      patients) or no pacemaker (23 patients). Inclusion criteria were >/=3 syncopes
      over the last 2 years and a positive cardioinhibitory (Vasovagal Syncope
      International Study types 2A and 2B) response to tilt testing. The median number
      of previous syncopal episodes was 6; asystolic response to tilt testing was
      present in 36 patients (86%) (mean asystole, 13.9+/-10.2 seconds). All patients
      were followed up for a minimum of 1.0 years and a maximum of 6.7 years (mean,
      3.7+/-2.2). One patient (5%) in the pacemaker arm experienced recurrence of
      syncope compared with 14 patients (61%) in the no-pacemaker arm (P=0.0006). In
      the no-pacemaker arm, the median time to first syncopal recurrence was 5 months,
      with a rate of 0.44 per year. On repeated tilt testing performed within 15 days
      after enrollment, positive responses were observed in 59% of patients with
      pacemakers and in 61% of patients without pacemakers (P=NS). CONCLUSIONS-In a
      limited, select group of patients with tilt-positive cardioinhibitory syncope,
      DDI pacing with hysteresis reduced the likelihood of syncope. The benefit of the
      therapy was maintained over the long term. Even in untreated patients, the
      syncopal recurrence burden was low. A negative result of tilt testing was not a
      useful means to evaluate therapy efficacy.

PMID- 10899093
TI  - Reduced ventricular response irregularity is associated with increased mortality
      in patients with chronic atrial fibrillation.
AB  - BACKGROUND-Variations in the ventricular response interval (VRI) during atrial
      fibrillation (AF) may be reduced in patients with adverse clinical outcomes. The
      properties of VRI dynamics associated with prognosis remain undetermined. METHODS
      AND RESULTS-In 107 patients with chronic AF (age, 64+/-9 years), we analyzed a 24
      hour ambulatory ECG for VRI variability (SD, SD of successive differences, and SD
      of 5-minute averages) and VRI irregularity (Shannon entropy of histogram,
      symbolic dynamics, and approximate entropy of beat-to-beat and minute-to-minute
      fluctuations [ApEn(b-b) and ApEn(m-m)]). During a follow-up period of 33+/-16
      months, 18 patients died (17%), 9 from cardiac causes, 7 from fatal strokes, and
      2 from malignancies. Reductions in all VRI variability and irregularity measures
      were associated with an increased risk for cardiac death but not for fatal
      stroke. A significant association with cardiac death was also found for ejection
      fraction (relative risk, 1.10; 95% confidence interval [CI], 1.04 to 1.17, per 1%
      decrement) and ischemic AF (relative risk, 6.52; 95% CI, 1.62 to 26. 3). After
      adjustment for these clinical variables, all irregularity measures except
      symbolic dynamics had predictive value (relative risks [95% CIs] per 1SD
      decrement: Shannon entropy of histogram, 2. 03 [1.14 to 3.61]; ApEn(b-b), 1.72
      [1.14 to 2.60]; and ApEn(m-m), 1. 90 [1.03 to 3.52]); however, the predictive
      power of variability measures was no longer significant. When the patients were
      stratified with the 33rd and 67th percentile values of ApEn(b-b) (1. 83 and 1.94,
      respectively), the 5-year cardiac mortality rates for the upper, middle, and
      lower tertiles were 0%, 13%, and 43%, respectively (log-rank test, P=0.04).
      CONCLUSIONS-Reduced VRI irregularity in a 24-hour ambulatory ECG has an
      independent prognostic value for cardiac mortality during long-term follow-up in
      patients with chronic AF.

PMID- 10899094
TI  - Two-year changes in blood pressure and subsequent risk of cardiovascular disease
      in men.
AB  - BACKGROUND-It is unclear whether, given a current blood pressure level, the
      previous 2-year change in blood pressure adds important predictive information
      for cardiovascular disease (CVD). METHODS AND RESULTS-We conducted a prospective
      cohort study of 11 150 middle-aged and older men reporting blood pressure in the
      Physicians' Health Study. These men had no history of CVD or antihypertensive
      medication use through the time of the 2-year follow-up questionnaire; after this
      time, follow-up for the current study began. A total of 905 incident cases of CVD
      (705 cases of coronary heart disease and 200 cases of stroke) occurred during a
      median follow-up of 10.8 years. After controlling for current blood pressure and
      other coronary risk factors, we found that previous 2-year changes in systolic
      blood pressure were not associated with the risk of CVD. A similar lack of
      association was found for individual end points of coronary heart disease and
      stroke. However, previous 2-year changes in diastolic blood pressure (DBP) may be
      inversely associated with the risk of CVD (linear trend, P=0.049) independent of
      coronary risk factors and current DBP. In subgroup analyses, previous 2-year
      blood pressure changes only added information in leaner men (body mass index
      <24.39 kg/m(2)). CONCLUSIONS-In this normotensive population of men, the prior 2
      year change in DBP, but not systolic blood pressure, may add information to
      current levels in relation to the risk of CVD. Clinicians may need to consider
      the previous pattern of DBP change when considering the risk associated with the
      current DBP level. These data require confirmation in other studies in which
      blood pressure is measured.

PMID- 10899095
TI  - Common carotid artery intima-media thickness and brain infarction : the Etude du
      Profil Genetique de l'Infarctus Cerebral (GENIC) case-control study. The GENIC
      Investigators.
AB  - BACKGROUND-The use of intima-media thickness (IMT) as an outcome measure in
      observational studies and intervention trials relies on the view that it reflects
      early stages of atherosclerosis and cardiovascular risk. There is little
      knowledge concerning the relation between IMT and brain infarction (BI). METHODS
      AND RESULTS-We investigated the relation of IMT with BI and its subtypes in 470
      cases and 463 controls. Cases with BI proven by MRI were consecutively recruited
      and classified into subtypes by cause of BI. Controls were recruited among
      individuals hospitalized at the same institutions and matched for age, sex, and
      center. IMT was measured at the far wall of both common carotid arteries (CCA)
      using an automatic detection system. Adventitia-to-adventitia diameters and CCA
      IMT were measured on transverse views; lumen diameter was computed using these
      measures. Mean (+/-SEM) CCA-IMT was higher in cases (0.797+/-0.006 mm) than in
      controls (0.735+/-0.006 mm; P<0. 0001). This difference remained after adjustment
      for lumen diameter and when analyses were restricted to subjects free of previous
      cardiovascular or cerebrovascular history. The difference in CCA-IMT between
      cases and controls was significant in the main subtypes. The risk of BI increased
      continuously with increasing CCA-IMT. The odds ratio per SD increase (0.150 mm)
      was 1.82 (95% confidence interval, 1.54 to 2.15); adjustment for cardiovascular
      risk factors slightly attenuated this relation (odds ratio, 1.73; 95% confidence
      interval, 1.45 to 2.07). CONCLUSIONS-An increased CCA-IMT was associated with BI,
      both overall and in the main subtypes. An increased IMT may help select patients
      at high risk for BI.

PMID- 10899096
TI  - Plasma disappearance of albumin and impact of capillary thickness in idiopathic
      dilated cardiomyopathy and after heart transplantation.
AB  - BACKGROUND-The increased plasma disappearance of albumin has previously been
      described in decompensated congestive heart failure (CHF); this disappearance
      normalized after diuretic treatment. Cardiac transplantation (HTX) and current
      medical treatment affect microvascular structure and function. We investigated
      the plasma disappearance of albumin and the impact of microvascular thickness and
      electrostatic properties in patients with compensated CHF and after HTX. METHODS
      AND RESULTS-The fraction of intravascular albumin that passes to the
      extravascular space per unit time, as determined from the plasma disappearance of
      intravenously injected (131)I-labeled albumin, was increased to 7.8+/-1.7% in 16
      patients with CHF compared with 18 controls (6.5+/-1.9%, P<0.05); these levels
      normalized after HTX (5.8+/-2.6%, P<0.01, n=17). The change in ratio between
      (131)I-albumin and simultaneously injected negatively charged glycosylated (125)I
      albumin (selectivity index, >1/hour in controls) was lower in patients with HTX
      (0.993+/-0. 022/hour) than in controls (1.008+/-0.019/hour; P<0.05), which
      indicated a relatively increased plasma disappearance of negatively charged
      albumin in HTX patients. Capillary basement membrane thickness was evaluated
      semiquantitatively from skin biopsies and showed no difference in the 3 groups
      (control, CHF, and HTX patients). However, in all 3 study groups, subjects with
      thicker capillary basement membranes had lower albumin escape rates (6.1+/-1. 8%,
      n=32, versus 7.6+/-2.6% in subjects without thickening of capillary basement
      membranes, n=19; P<0.05). CONCLUSIONS-The plasma disappearance of albumin
      increased in patients with compensated CHF and it normalized after HTX. The
      present normalized capillary basement thicknesses in patients with CHF and the
      direct association between this parameter and plasma albumin disappearance
      indicate that previous compensatory microvascular basement membrane growth
      results in restricted permeability. Microvascular electrostatic properties did
      not relate to plasma albumin disappearance.

PMID- 10899097
TI  - Tumor necrosis factor-alpha is expressed in donor heart and predicts right
      ventricular failure after human heart transplantation.
AB  - BACKGROUND-Myocardial failure is an important problem after heart
      transplantation. Right ventricular (RV) failure is most common, although its
      mechanisms remain poorly understood. Inflammatory cytokines play an important
      role in heart failure. We studied the expression of tumor necrosis factor (TNF)
      alpha and other cytokines in donor myocardium and their relationship to the
      subsequent development of RV failure early after transplantation. METHODS AND
      RESULTS-Clinical details were obtained, and ventricular function was assessed by
      transesophageal echocardiography in 26 donors before heart retrieval. A donor RV
      biopsy was obtained immediately before transplantation, and each recipient was
      followed for the development of RV failure. Reverse transcriptase-polymerase
      chain reaction was performed to detect TNF-alpha, interleukin-2, interferon
      gamma, and inducible nitric oxide synthase expression. Eight of 26 recipients
      (30.8%) developed RV failure. Seven of these 8 (87.5%) expressed TNF-alpha, but
      only 4 of the 18 (22.2%) who did not develop RV failure expressed TNF-alpha
      (P<0.005). As a predictor of RV failure, TNF-alpha mRNA had a sensitivity of
      87.5%, a specificity of 83.3%, a positive predictive value of 70%, and a negative
      predictive value of 93.7%. Western blotting demonstrated more TNF-alpha protein
      in the myocardium of donor hearts that developed RV failure (658+/-60 versus
      470+/-57 optical density units, P<0.05). Immunocytochemistry localized TNF-alpha
      expression to cardiac myocytes. Reverse transcriptase-polymerase chain reaction
      detected interferon-gamma in 2 (7.7%), interleukin-2 in 1 (3.8%), and inducible
      nitric oxide synthase mRNA in 1 (3.8%) of the 26 donor hearts, none of which
      developed RV failure. CONCLUSIONS-TNF-alpha expression in donor heart cardiac
      myocytes seems to predict the development of RV failure in patients early after
      heart transplantation.

PMID- 10899098
TI  - Thrombomodulin overexpression to limit neointima formation.
AB  - BACKGROUND-These studies were initiated to confirm that high-level thrombomodulin
      overexpression is sufficient to limit neointima formation after mechanical
      overdilation injury. METHODS AND RESULTS-An adenoviral construct expressing
      thrombomodulin (Adv/RSV-THM) was created and functionally characterized in vitro
      and in vivo. The impact of local overexpression of thrombomodulin on neointima
      formation 28 days after mechanical overdilation injury was evaluated. New Zealand
      White rabbit common femoral arteries were treated with buffer, viral control, or
      Adv/RSV-THM and subjected to mechanical overdilation injury. The treated vessels
      (n=4 per treatment) were harvested after 28 days and evaluated to determine
      intima-to-media (I/M) ratios. Additional experiments were performed to determine
      early (7-day) changes in extracellular elastin and collagen content; local
      macrophage, T-cell, and neutrophil infiltration; and local thrombus formation as
      potential contributors to the observed impact on 28-day neointima formation. The
      construct significantly decreased neointima formation after mechanical dilation
      injury in this model. By histological analysis, buffer controls exhibited mean
      I/M ratios of 0.76+/-0.06%, whereas viral controls reached 0.77+/-0.08%; in
      contrast, Adv/RSV-THM reduced I/M ratios to 0.47+/-0.06%. Local inflammatory
      infiltrate decreased in the Adv/RSV-THM group relative to controls, whereas
      matrix remained relatively preserved. Rates of early thrombus formation also
      decreased in Adv/RSV-THM animals. CONCLUSIONS-This construct thus offers a viable
      technique for promoting a locally neointima-resistant small-caliber artery via
      decreased thrombus bulk, normal matrix preservation, and decreased local
      inflammation without the inflammatory damage that has limited many other
      adenoviral applications.

PMID- 10899099
TI  - Mechanical unloading versus neurohumoral stimulation on myocardial structure and
      endocrine function In vivo.
AB  - BACKGROUND-Mechanical load and humoral stimuli such as endothelin (ET) and
      angiotensin II (Ang II) are potent modulators of cardiac structure and endocrine
      function, specifically gene expression and production and release of atrial
      natriuretic peptide (ANP). We define the contribution of mechanical load compared
      with neurohumoral stimulation in vivo with specific focus on myocardial and
      circulating ANP during chronic myocardial unloading produced by thoracic inferior
      vena caval constriction (TIVCC). METHODS AND RESULTS-TIVCC was produced by
      banding the IVC for 10 days in 7 dogs, whereas in the 6 control dogs, the band
      was not constricted. TIVCC was characterized by a decrease in cardiac output,
      right atrial pressure, and left ventricular (LV) end-diastolic diameter and
      marked activation of ET and Ang II in plasma and atrial and ventricular
      myocardium. Despite neurohumoral stimulation, LV mass index and myocyte diameters
      in unloaded hearts decreased, reflecting myocyte atrophy. The total number of
      myocytes in the LV remained unchanged. Atrial stores of ANP increased, but plasma
      ANP did not change, in association with a trend toward ANP gene expression to
      decrease in unloaded hearts. CONCLUSIONS-Chronic mechanical unloading of the
      heart results in myocardial atrophy and lack of activation of ANP synthesis
      despite marked neurohumoral stimulation by the growth promoters ET and Ang II.

PMID- 10899100
TI  - Beta-adrenergic receptor subtypes differentially affect apoptosis in adult rat
      ventricular myocytes.
AB  - BACKGROUND-Catecholamine-induced apoptosis is mediated by activation of the beta
      adrenergic signaling pathway. We tested the hypothesis that beta(1)- and beta(2)
      adrenergic receptor (AR) subtypes differentially affect apoptosis in adult rat
      ventricular myocytes in vitro. METHODS AND RESULTS-Myocytes were first exposed to
      norepinephrine (NE) alone (10 mcmol/L) or NE+atenolol (AT) (10 mcmol/L) for 12
      hours. AT, a beta(1)-selective AR antagonist, abolished the NE-induced increase
      in nick end-labeling (TUNEL)-positive cells compared with control (NE, 33+/-3%
      versus control, 3+/-1%, P<0.0001; NE+AT, 4+/-2% versus control, 3+/-1%, P=0. 98).
      Annexin V staining, DNA laddering, and caspase activity determinations
      corroborated these results. Subsequent experiments under prazosin treatment
      established the apoptosis dose-response curves for the increasingly beta(2)
      selective AR agonists isoproterenol (ISO) (beta(1) approximately beta(2)) and
      albuterol (ALB) (beta(2)>beta(1)). ISO and ALB induced significantly less
      apoptosis than NE (beta(1)>beta(2)) at equimolar concentrations as assessed by
      TUNEL staining [1 mcmol/L: NE (8+/-2%) approximately ISO (7+/-1%)>ALB (2+/-1%);
      10 mcmol/L: NE (35+/-2%)>ISO (23+/-1%)>ALB (3+/-1%); 100 mcmol/L: NE (50+/
      2%)>ISO (29+/-2%)>ALB (14+/-1%), P<0.0001 except for NE versus ISO at 1 mcmol/L
      with P=0.62]. ALB-induced apoptosis at 100 mcmol/L was abolished by AT (10
      mcmol/L), indicating a beta(1)AR-mediated effect. Importantly, ICI 118551 (0.1
      mcmol/L), a highly selective beta(2)AR antagonist, did not decrease the
      percentage of NE-, ISO-, and ALB-induced apoptosis. Reverse transcription
      polymerase chain reaction studies revealed that AT completely reversed the beta
      adrenergic signaling-induced changes in the Bcl-2-to-Bax ratio. CONCLUSIONS-These
      observations provide evidence that beta AR-mediated apoptotic death signaling is
      largely dissociated from beta(2)ARs and selectively mediated by beta(1)ARs in
      adult rat ventricular myocytes.

PMID- 10899101
TI  - Improvement of endothelial function by chronic angiotensin-converting enzyme
      inhibition in heart failure : role of nitric oxide, prostanoids, oxidant stress,
      and bradykinin.
AB  - BACKGROUND-Chronic heart failure (CHF) impairs the endothelium-dependent, flow
      mediated dilation (FMD) of small arteries. However, whether chronic angiotensin
      converting enzyme (ACE) inhibition affects the impairment of FMD in CHF is
      unknown. We investigated the effects of long-term ACE inhibition on the FMD of
      peripheral arteries in rats with CHF and the mechanism(s) involved. METHODS AND
      RESULTS-FMD was assessed in isolated, perfused gracilis muscle arteries from sham
      operated, and untreated or ACE inhibitor-treated (perindopril 2 mg. kg(-1). day(
      1) for 10 weeks) rats with CHF (coronary artery ligation). The role of nitric
      oxide (NO), prostaglandins, and free radicals was assessed by pretreating the
      vessels with the NO synthase inhibitor N(W)-nitro-L-arginine, the cyclooxygenase
      inhibitor diclofenac, or the free radical scavenger N-2-mercaptopropionyl-glycine
      (MPG). Endothelial NO synthase mRNA expression was determined by reverse
      transcriptase polymerase chain reaction. In animals with hemodynamic and
      echographic signs of CHF, FMD was converted into vasoconstriction, and this was
      prevented by ACE inhibition. FMD of arteries from sham-operated or ACE inhibitor
      treated CHF rats was abolished by N(W)-nitro-L-arginine. In untreated CHF rats,
      FMD was increased by diclofenac and MPG. In contrast, in arteries from ACE
      inhibitor-treated rats, neither diclofenac nor MPG affected FMD. In parallel, ACE
      inhibition prevented the reduction of endothelial NO synthase mRNA by CHF.
      CONCLUSIONS-In CHF, ACE inhibition normalized NO-dependent dilatation and
      suppressed the production of vasoconstrictor prostanoid(s), resulting in improved
      FMD. The improvement of FMD might contribute to the beneficial effects of ACE
      inhibition during CHF.

PMID- 10899102
TI  - Hirudin reduces tissue factor expression and attenuates graft arteriosclerosis in
      rat cardiac allografts.
AB  - BACKGROUND-Intravascular clotting has been implicated in the pathogenesis of
      cardiac allograft vasculopathy (CAV). We previously identified the expression of
      tissue factor (TF), the primary cellular initiator of blood coagulation, within
      the coronary intima, which was associated with neointimal thickening. In the
      present study, the effect of recombinant hirudin on CAV was assessed in Lewis to
      Fisher rat heterotopic cardiac allografts. METHODS AND RESULTS-Transplant
      recipients were randomized to a control group (n=10) and a hirudin-treated group
      (n=12; 2 mg. kg(-1). d(-1) SC). Histological evaluations of rejection, CAV, and
      TF staining were performed 120 days after transplantation. No significant
      differences were observed between the 2 groups with respect to the degree of
      rejection. Hirudin significantly (P<0.05) suppressed the development of CAV in
      the graft microvessels, but it was less effective in large coronary arteries.
      Graft intimal cells, isolated by laser-assisted cell picking, showed a marked
      upregulation of TF gene transcription, which was prevented by hirudin (P<0.01).
      As demonstrated by immunohistochemistry and quantitative analyses of TF mRNA
      levels by real-time polymerase chain reaction, hirudin treatment resulted in a
      significant reduction of TF protein and mRNA expression (P<0.001). CONCLUSIONS
      Treatment with hirudin in this rat cardiac transplant model inhibited TF
      expression and decreased neointimal hyperplasia. These results suggest that TF
      inhibition by hirudin, in addition to its direct effect on thrombin, may
      attenuate the hypercoagulable state and prevent the development of CAV at least
      in restricted sites of the graft coronary vasculature.

PMID- 10899103
TI  - Images in cardiovascular medicine. Augmentation of coronary blood flow with intra
      aortic balloon pump counter-pulsation.

PMID- 10899104
TI  - Helical velocity patterns in a human coronary artery: a three-dimensional
      computational fluid dynamic reconstruction showing the relation with local wall
      thickness.

PMID- 10899105
TI  - International conference spotlights disaster in sub-Saharan Africa.

PMID- 10899106
TI  - Crystal structure of the conserved core of protein arginine methyltransferase
      PRMT3.
AB  - Protein arginine methylation has been implicated in signal transduction, nuclear
      transport and transcription regulation. Protein arginine methyltransferases
      (PRMTs) mediate the AdoMet-dependent methylation of many proteins, including many
      RNA binding proteins involved in various aspects of RNA processing and/or
      transport. Here we describe the crystal structure of the rat PRMT3 catalytic core
      in complex with reaction product AdoHcy, determined at 2.0 A resolution. The
      results reveal a two-domain structure: an AdoMet-binding domain and a barrel-like
      domain. The AdoMet-binding domain is a compact version of the consensus AdoMet
      dependent methyltransferase fold. The active site is situated in a cone-shaped
      pocket between the two domains. The residues that make up the active site are
      conserved across the PRMT family, consisting of a double-E loop containing two
      invariant Glu and one His-Asp proton-relay system. The structure suggests a
      mechanism for the methylation reaction and provides the structural basis for
      functional characterization of the PRMT family. In addition, crystal packing and
      solution behavior suggest dimer formation of the PRMT3 core.

PMID- 10899107
TI  - Structural basis for activation of alpha-boranophosphate nucleotide analogues
      targeting drug-resistant reverse transcriptase.
AB  - AIDS chemotherapy is limited by inadequate intracellular concentrations of the
      active triphosphate form of nucleoside analogues, leading to incomplete
      inhibition of viral replication and the appearance of drug-resistant virus. Drug
      activation by nucleoside diphosphate kinase and inhibition of HIV-1 reverse
      transcriptase were studied comparatively. We synthesized analogues with a borano
      (BH(3)(-)) group on the alpha-phosphate, and found that they are substrates for
      both enzymes. X-ray structures of complexes with nucleotide diphosphate kinase
      provided a structural basis for their activation. The complex with d4T
      triphosphate displayed an intramolecular CH.O bond contributing to catalysis, and
      the R(p) diastereoisomer of thymidine alpha-boranotriphosphate bound like a
      normal substrate. Using alpha-(R(p))-boranophosphate derivatives of the
      clinically relevant compounds AZT and d4T, the presence of the alpha-borano group
      improved both phosphorylation by nucleotide diphosphate kinase and inhibition of
      reverse transcription. Moreover, repair of blocked DNA chains by
      pyrophosphorolysis was reduced significantly in variant reverse transcriptases
      bearing substitutions found in drug-resistant viruses. Thus, the alpha-borano
      modification of analogues targeting reverse transcriptase may be of generic value
      in fighting viral drug resistance.

PMID- 10899108
TI  - Charged residues dominate a unique interlocking topography in the heterodimeric
      cytokine interleukin-12.
AB  - Human interleukin-12 (IL-12, p70) is an early pro-inflammatory cytokine,
      comprising two disulfide-linked subunits, p35 and p40. We solved the crystal
      structures of monomeric human p40 at 2.5 A and the human p70 complex at 2.8 A
      resolution, which reveals that IL-12 is similar to class 1 cytokine-receptor
      complexes. They also include the first description of an N-terminal
      immunoglobulin-like domain, found on the p40 subunit. Several charged residues
      from p35 and p40 intercalate to form a unique interlocking topography, shown by
      mutagenesis to be critical for p70 formation. A central arginine residue from p35
      projects into a deep pocket on p40, which may be an ideal target for a small
      molecule antagonist of IL-12 formation.

PMID- 10899109
TI  - Expression of ram-5 in the structural cell is required for sensory ray
      morphogenesis in Caenorhabditis elegans male tail.
AB  - Tissue morphogenesis requires complex cellular interaction and communication. The
      sensory ray in the Caenorhabditis elegans male tail has a simple cellular make-up
      and a non-essential function, thus providing an ideal model for studying the
      mechanisms guiding morphogenesis. We present here the analysis of a novel gene,
      ram-5, mutations of which are characterized by abnormal lumpy rays in the male
      tail. Microscopic analysis and behavioral studies revealed that lumpy rays
      contain operational sensory neurons. However, abnormalities were observed in the
      hypodermis and structural cells as well as in appositions between these two cell
      types. Molecular cloning and expression studies revealed that the ram-5 gene
      encodes a transmembrane protein localized in sensory ray support cells, the
      structural cells. Expression of ram-5 in these cells is required for normal ray
      morphogenesis. ram-5-dependent cell-cell communication is implicated in
      organizing the structural cell and the hypodermis, potentially through adhesion
      at the structural cell-hypodermal cell border.

PMID- 10899110
TI  - Vacuolar uptake of host components, and a role for cholesterol and sphingomyelin
      in malarial infection.
AB  - Erythrocytes, which are incapable of endocytosis or phagocytosis, can be infected
      by the malaria parasite Plasmodium falciparum. We find that a transmembrane
      protein (Duffy), glycosylphosphatidylinositol (GPI)-anchored and cytoplasmic
      proteins, associated with detergent-resistant membranes (DRMs) that are
      characteristic of microdomains in host cell membranes, are internalized by
      vacuolar parasites, while the major integral membrane and cytoskeletal proteins
      are not. The internalized host proteins and a plasmodial transmembrane resident
      parasitophorous vacuolar membrane (PVM) protein are detected in DRMs associated
      with vacuolar parasites. This is the first report of a host transmembrane protein
      being recruited into an apicomplexan vacuole and of the presence of vacuolar
      DRMs; it establishes that integral association does not preclude protein
      internalization into the P.FALCIPARUM: vacuole. Rather, as shown for Duffy,
      intracellular accumulation occurs at the same rate as that seen for a DRM
      associated GPI-anchored protein. Furthermore, novel mechanisms regulated by the
      DRM lipids, sphingomyelin and cholesterol, mediate (i) the uptake of host DRM
      proteins and (ii) maintenance of the intracellular vacuole in the non-endocytic
      red cell, which may have implications for intracellular parasitism and
      pathogenesis.

PMID- 10899111
TI  - Discrimination of GLUT4 vesicle trafficking from fusion using a temperature
      sensitive Munc18c mutant.
AB  - To examine the temporal relationship between pre- and post-docking events, we
      generated a Munc18c temperature-sensitive mutant (Munc18c/TS) by substitution of
      arginine 240 with a lysine residue. At the permissive temperature (23 degrees C),
      overexpression of both the wild type (Munc18c/WT) and the R240K mutant inhibited
      insulin-stimulated GLUT4/IRAP vesicle translocation. However, at the non
      permissive temperature (37 degrees C) only Munc18c/WT inhibited GLUT4/IRAP
      translocation whereas Munc18c/TS was without effect. Moreover, Munc18c/WT bound
      to syntaxin 4 at both 23 and 37 degrees C whereas Munc18c/TS bound syntaxin 4
      only at 23 degrees C. This was due to a temperature-dependent conformational
      change in Munc18c/TS, as its ability to bind syntaxin 4 and effects on GLUT4
      translocation were rapidly reversible while protein expression levels remained
      unchanged. Furthermore, insulin stimulation of Munc18c/TS-expressing cells at 23
      degrees C followed by temperature shift to 37 degrees C resulted in an increased
      rate of GLUT4 translocation compared with cells stimulated at 37 degrees C. To
      date, this is the first demonstration that the rate-limiting step for insulin
      stimulated GLUT4 translocation is the trafficking of GLUT4 vesicles and not their
      fusion with the plasma membrane.

PMID- 10899112
TI  - Measles virus matrix protein specifies apical virus release and glycoprotein
      sorting in epithelial cells.
AB  - In polarized epithelial cells measles virus (MV) is predominantly released at the
      apical cell surface, irrespective of the sorting of its two envelope
      glycoproteins F and H. It has been reported previously that the viral matrix (M)
      protein modulates the fusogenic capacity of the viral envelope glycoproteins.
      Here, extant MV mutants and chimeras were used to determine the role of M protein
      in the transport of viral glycoproteins and release of progeny virions in
      polarized epithelial CaCo2 cells. In the absence of M, envelope glycoproteins are
      sorted to the basolateral surface, suggesting that they possess intrinsic
      basolateral sorting signals. However, interactions of M with the glycoprotein
      cytoplasmic tails allow M-glycoprotein co-segregation to the apical surface,
      suggesting a vectorial function of M to retarget the glycoproteins for apical
      virion release. Whereas this may allow virus airway shedding, the intrinsic
      sorting of the glycoproteins to the basolateral surface may account for systemic
      host infection by allowing efficient cell-cell fusion.

PMID- 10899113
TI  - Munc13-1 acts as a priming factor for large dense-core vesicles in bovine
      chromaffin cells.
AB  - In chromaffin cells the number of large dense-core vesicles (LDCVs) which can be
      released by brief, intense stimuli represents only a small fraction of the
      'morphologically docked' vesicles at the plasma membrane. Recently, it was shown
      that Munc13-1 is essential for a post-docking step of synaptic vesicle fusion. To
      investigate the role of Munc13-1 in LDCV exocytosis, we overexpressed Munc13-1 in
      chromaffin cells and stimulated secretion by flash photolysis of caged calcium.
      Both components of the exocytotic burst, which represent the fusion of release
      competent vesicles, were increased by a factor of three. The sustained component,
      which represents vesicle maturation and subsequent fusion, was increased by the
      same factor. The response to a second flash, however, was greatly reduced,
      indicating a depletion of release-competent vesicles. Since there was no apparent
      change in the number of docked vesicles, we conclude that Munc13-1 acts as a
      priming factor by accelerating the rate constant of vesicle transfer from a pool
      of docked, but unprimed vesicles to a pool of release-competent, primed vesicles.

PMID- 10899114
TI  - NAIP interacts with hippocalcin and protects neurons against calcium-induced cell
      death through caspase-3-dependent and -independent pathways.
AB  - Inhibitor-of-apoptosis proteins (IAPs), including neuronal apoptosis inhibitory
      protein (NAIP), inhibit cell death. Other IAPs inhibit key caspase proteases
      which effect cell death, but the mechanism by which NAIP acts is unknown. Here we
      report that NAIP, through its third baculovirus inhibitory repeat domain (BIR3),
      binds the neuron-restricted calcium-binding protein, hippocalcin, in an
      interaction promoted by calcium. In neuronal cell lines NSC-34 and Neuro-2a, over
      expression of the BIR domains of NAIP (NAIP-BIR1-3) counteracted the calcium
      induced cell death induced by ionomycin and thapsigargin. This protective
      capacity was significantly enhanced when NAIP-BIR1-3 was co-expressed with
      hippocalcin. Over-expression of the BIR3 domain or hippocalcin alone did not
      substantially enhance cell survival, but co-expression greatly increased their
      protective effects. These data suggest synergy between NAIP and hippocalcin in
      facilitating neuronal survival against calcium-induced death stimuli mediated
      through the BIR3 domain. Analysis of caspase activity after thapsigargin
      treatment revealed that caspase-3 is activated in NSC-34, but not Neuro-2a,
      cells. Thus NAIP, in conjunction with hippocalcin, can protect neurons against
      calcium-induced cell death in caspase-3-activated and non-activated pathways.

PMID- 10899115
TI  - Phasic characteristic of elementary Ca(2+) release sites underlies quantal
      responses to IP(3).
AB  - Ca(2+) liberation by inositol 1,4,5-trisphosphate (IP(3)) is 'quantal', in that
      low [IP(3)] causes only partial Ca(2+) release, but further increasing [IP(3)]
      evokes more release. This characteristic allows cells to generate graded Ca(2+)
      signals, but is unexpected, given the regenerative nature of Ca(2+)-induced
      Ca(2+) release through IP(3) receptors. Two models have been proposed to resolve
      this paradox: (i) all-or-none Ca(2+) release from heterogeneous stores that empty
      at varying [IP(3)]; and (ii) phasic liberation from homogeneously sensitive
      stores. To discriminate between these hypotheses, we imaged subcellular Ca(2+)
      puffs evoked by IP(3) in Xenopus oocytes where release sites were functionally
      uncoupled using EGTA. Puffs were little changed by 300 microM intracellular EGTA,
      but sites operated autonomously and did not propagate waves. Photoreleased IP(3)
      generated flurries of puffs-different to the prolonged Ca(2+) elevation following
      waves in control cells-and individual sites responded repeatedly to successive
      increments of [IP(3)]. These data support the second hypothesis while refuting
      the first, and suggest that local Ca(2+) signals exhibit rapid adaptation,
      different to the slower inhibition following global Ca(2+) waves.

PMID- 10899116
TI  - Identification and characterization of a highly conserved calcineurin binding
      protein, CBP1/calcipressin, in Cryptococcus neoformans.
AB  - Calcineurin is the conserved target of the immunosuppressants cyclosporin A and
      FK506. Using the yeast two-hybrid system, we identified a novel calcineurin
      binding protein, CBP1, from the pathogenic fungus Cryptococcus neoformans. We
      show that CBP1 binds to calcineurin in vitro and in vivo, and FKBP12-FK506
      inhibits CBP1 binding to calcineurin. Cryptococcus neoformans cbp1 mutant strains
      exhibit modest defects in growth under stress conditions and virulence, similar
      to but less severe than the phenotypes of calcineurin mutants. Saccharomyces
      cerevisiae mutants lacking the CBP1 homolog RCN1 are, like calcineurin mutants,
      sensitive to lithium cation stress. CBP1 shares a central peptide sequence motif,
      SPPxSPP, with related proteins in S.CEREVISIAE:, Schizosaccharomyces pombe,
      Drosophila melanogaster, Caenorhabditis elegans and humans, and peptides
      containing this motif altered calcineurin activity in vitro. Interestingly, the
      human CBP1 homolog DSCR1 is encoded by the Down's syndrome candidate region
      interval on chromosome 21, is highly expressed in the heart and central nervous
      system, and may play a role in calcineurin functions in heart development,
      neurite extension and memory.

PMID- 10899117
TI  - Potential role of PKR in double-stranded RNA-induced macrophage activation.
AB  - In this study, the role of the double-stranded (ds) RNA-dependent protein kinase
      (PKR) in macrophage activation was examined. dsRNA [polyinosinic:polycytidylic
      acid (poly IC)]-stimulated inducible nitric oxide synthase, interleukin (IL)
      1alpha and IL-1beta mRNA expression, nitrite formation and IL-1 release are
      attenuated in RAW264.7 cells stably expressing dominant negative (dn) mutants of
      PKR. The transcriptional regulator nuclear factor (NF)-kappaB is activated by
      dsRNA, and appears to be required for dsRNA-induced macrophage activation. While
      dnPKR mutants prevent macrophage activation, they fail to attenuate dsRNA-induced
      IkappaB degradation or NF-kappaB nuclear localization. The inhibitory actions of
      dnPKR on dsRNA-induced macrophage activation can be overcome by treatment with
      interferon (IFN)-gamma, an event associated with PKR degradation. Furthermore,
      dsRNA + IFN-gamma stimulate inducible nitric oxide synthase expression, IkappaB
      degradation and NF-kappaB nuclear localization to similar levels in macrophages
      isolated from PKR(-/-) and PKR(+/+) mice. These findings indicate that both NF
      kappaB and PKR are required for dsRNA-induced macrophage activation; however,
      dsRNA-induced NF-kappaB activation occurs by PKR-independent mechanisms in
      macrophages. In addition, the PKR dependence of dsRNA-induced macrophage
      activation can be overcome by IFN-gamma.

PMID- 10899118
TI  - Coupling ion specificity of chimeras between H(+)- and Na(+)-driven motor
      proteins, MotB and PomB, in Vibrio polar flagella.
AB  - We have shown that a hybrid motor consisting of proton-type Rhodobacter
      sphaeroides MotA and sodium-type VIBRIO: alginolyticus PomB, MotX and MotY, can
      work as a sodium-driven motor in VIBRIO: cells. In this study, we tried to
      substitute the B subunits, which contain a putative ion-binding site in the
      transmembrane region. Rhodobacter sphaeroides MotB did not work with either MotA
      or PomA in Vibrio cells. Therefore, we constructed chimeric proteins (MomB),
      which had N-terminal MotB and C-terminal PomB. MomB proteins, with the entire
      transmembrane region derived from the H(+)-type MotB, gave rise to an Na(+) motor
      with MotA. The other two MomB proteins, in which the junction sites were within
      the transmembrane region, also formed Na(+) motors with PomA, but were changed
      for Na(+) or Li(+) specificity. These results show that the channel part
      consisting of the transmembrane regions from the A and B subunits can interchange
      Na(+)- and H(+)-type subunits and this can affect the ion specificity. This is
      the first report to have changed the specificity of the coupling ions in a
      bacterial flagellar motor.

PMID- 10899119
TI  - On the binding mechanism of the peptide receptor of the oligopeptide transport
      system of Lactococcus lactis.
AB  - Lactococcus lactis degrades exogenous proteins such as beta-casein to peptides of
      4-30 amino acids, and uses these as nitrogen sources. The binding protein or
      receptor (OppA(Ll)) of the oligopeptide transport system (Opp) of L.LACTIS: has
      the unique capacity to bind peptides from five up to at least 20 residues. To
      study the binding mechanism of OppA(Ll), nonameric peptides were used in which
      the cysteine at position 1, 3, 4, 5, 6, 7 or 9 was selectively labeled with
      either bulky and non-fluorescent or bulky and fluorescent groups. Also, nonameric
      peptides with a non-natural residue, azatryptophan, at positions 3 or 7 were
      used. The fluorescence of azatryptophan reports on the polarity of the
      environment. The studies indicate that the binding protein encloses the first six
      amino acids of the peptide, whereas the remaining residues stick out and interact
      with the surface of the binding protein. The peptide binding mechanism of
      OppA(Ll) is discussed in relation to known three-dimensional structures of
      members of this class of proteins, and an adaptation of the general binding
      mechanism is proposed.

PMID- 10899120
TI  - Role of the spindle pole body of yeast in mediating assembly of the prospore
      membrane during meiosis.
AB  - Spindle pole bodies (SPBs) are the centrosome equivalents in yeast, required for
      microtubule organization. In yeast, the SPB further serves as the attachment
      sites of the prospore membrane during meiosis. Here we report the identification
      of two new meiosis-specific components of the SPB, Mpc54p and Mpc70p, and the
      first protein specific for the prospore membrane, Don1p. Mpc54p and Mpc70p are
      not present in mitotic SPBs, and during meiosis II they are components of a
      meiosis-specific structural alteration of the outer plaque of the SPB. Both
      proteins are dispensable for the meiotic divisions but are essentially required
      for the formation of the prospore membrane. In the mpc54 and mpc70 mutants, the
      Don1p-containing precursors of the prospore membrane can still be found in the
      cytoplasm and associated with the SPB. Unexpectedly, however, the assembly of the
      precursors to a continuous membrane system is affected. Thus, the meiotic SPB is
      directly involved in the formation of a specialized membrane system, the membrane
      of the prospore.

PMID- 10899121
TI  - Mast, a conserved microtubule-associated protein required for bipolar mitotic
      spindle organization.
AB  - Through mutational analysis in Drosopjila we have identified the gene multiple
      asters (mast), which encodes a new 165 kDa protein. mast mutant neuroblasts are
      highly polyploid and show severe mitotic abnormalities including the formation of
      mono- and multi-polar spindles organized by an irregular number of microtubule
      organizing centres of abnormal size and shape. The mast gene product is
      evolutionarily conserved since homologues were identified from yeast to man,
      revealing a novel protein family. Antibodies against Mast and analysis of tissue
      culture cells expressing an enhanced green fluorescent protein-Mast fusion
      protein show that during mitosis, this protein localizes to centrosomes, the
      mitotic spindle, centromeres and spindle midzone. Microtubule-binding assays
      indicate that Mast is a microtubule-associated protein displaying strong affinity
      for polymerized microtubules. The defects observed in the mutant alleles and the
      intracellular localization of the protein suggest that Mast plays an essential
      role in centrosome separation and organization of the bipolar mitotic spindle.

PMID- 10899122
TI  - RNA-dependent cytoplasmic anchoring of a transcription factor subunit during
      Xenopus development.
AB  - The CCAAT box transcription factor (CBTF) is a multimeric transcription factor
      that activates expression of the haematopoietic regulatory factor, GATA-2. The
      122 kDa subunit of this complex, CBTF(122), is cytoplasmic in fertilized Xenopus
      eggs and subsequently translocates to the nucleus prior to activation of zygotic
      GATA-2 transcription at gastrulation. Here we present data suggesting both a role
      for CBTF(122) prior to its nuclear translocation and the mechanism that retains
      it in the cytoplasm before the midblastula transition (MBT). CBTF(122) and its
      variant CBTF(98) are associated with translationally quiescent mRNP complexes. We
      show that CBTF(122) RNA binding activity is both necessary and sufficient for its
      cytoplasmic retention during early development. The introduction of an additional
      nuclear localization signal to CBTF(122) is insufficient to overcome this
      retention, suggesting that RNA binding acts as a cytoplasmic anchor for
      CBTF(122). Destruction of endogenous RNA by microinjection of RNase promotes
      premature nuclear translocation of CBTF(122). Thus, the nuclear translocation of
      CBTF(122) at the MBT is likely to be coupled to the degradation of maternal mRNA
      that occurs at that stage.

PMID- 10899123
TI  - Protein interaction surface of the POU transcription factor UNC-86 selectively
      used in touch neurons.
AB  - The Caenorhabditis elegans POU protein UNC-86 specifies the HSN motor neurons,
      which are required for egg-laying, and six mechanosensory neurons. To investigate
      how UNC-86 controls neuronal specification, we characterized two unc-86 mutants
      that do not respond to touch but show wild-type egg-laying behavior. Residues
      P145 and L195, which are altered by these mutations, are located in the POU
      specific domain and abolish the physical interaction of UNC-86 with the LIM
      homeodomain protein, MEC-3. This results in a failure to maintain mec-3
      expression and in loss of expression of the mechanosensory neuron-specific gene,
      mec-2. unc-86-dependent expression of genes in other neurons is not impaired. We
      conclude that distinct residues in the POU domain of UNC-86 are involved in
      modulating UNC-86 activity during its specification of different neurons. A
      structural model of the UNC-86 POU domain, including base pairs and amino acid
      residues required for MEC-3 interaction, revealed that P145 and L195 are part of
      a hydrophobic pocket which is similar to the OCA-B-binding domain of the
      mammalian POU protein, Oct-1.

PMID- 10899124
TI  - A dual role for zinc fingers in both DNA binding and zinc sensing by the Zap1
      transcriptional activator.
AB  - The Zap1 transcriptional activator of Saccharomyces cerevisiae controls zinc
      homeostasis. Zap1 induces target gene expression in zinc-limited cells and is
      repressed by high zinc. One such target gene is ZAP1 itself. In this report, we
      examine how zinc regulates Zap1 function. First, we show that transcriptional
      autoregulation of Zap1 is a minor component of zinc responsiveness; most
      regulation of Zap1 activity occurs post-translationally. Secondly, nuclear
      localization of Zap1 does not change in response to zinc, suggesting that zinc
      regulates DNA binding and/or activation domain function. To understand how Zap1
      responds to zinc, we performed a functional dissection of the protein. Zap1
      contains two activation domains. DNA-binding activity is conferred by five C
      terminal C(2)H(2) zinc fingers and each finger is required for high-affinity DNA
      binding. The zinc-responsive domain of Zap1 also maps to the C-terminal zinc
      fingers. Furthermore, mutations that disrupt some of these fingers cause
      constitutive activity of a bifunctional Gal4 DNA-binding domain-Zap1 fusion
      protein. These results demonstrate a novel function of Zap1 zinc fingers in zinc
      sensing as well as DNA binding.

PMID- 10899125
TI  - Phosphoacetylation of histone H3 on c-fos- and c-jun-associated nucleosomes upon
      gene activation.
AB  - The induction of immediate-early (IE) genes, including proto-oncogenes c-fos and
      c-jun, correlates well with a nucleosomal response, the phosphorylation of
      histone H3 and HMG-14 mediated via extracellular signal regulated kinase or p38
      MAP kinase cascades. Phosphorylation is targeted to a minute fraction of histone
      H3, which is also especially susceptible to hyperacetylation. Here, we provide
      direct evidence that phosphorylation and acetylation of histone H3 occur on the
      same histone H3 tail on nucleosomes associated with active IE gene chromatin.
      Chromatin immunoprecipitation (ChIP) assays were performed using antibodies that
      specifically recognize the doubly-modified phosphoacetylated form of histone H3.
      Analysis of the associated DNA shows that histone H3 on c-fos- and c-jun
      associated nucleosomes becomes doubly-modified, the same H3 tails becoming both
      phosphorylated and acetylated, only upon gene activation. This study reveals
      potential complications of occlusion when using site-specific antibodies against
      modified histones, and shows also that phosphorylated H3 is more sensitive to
      trichostatin A (TSA)-induced hyperacetylation than non-phosphorylated H3. Because
      MAP kinase-mediated gene induction is implicated in controlling diverse
      biological processes, histone H3 phosphoacetylation is likely to be of widespread
      significance.

PMID- 10899126
TI  - The Ess1 prolyl isomerase is linked to chromatin remodeling complexes and the
      general transcription machinery.
AB  - The Ess1/Pin1 peptidyl-prolyl isomerase (PPIase) is thought to control mitosis by
      binding to cell cycle regulatory proteins and altering their activity. Here we
      isolate temperature-sensitive ess1 mutants and identify six multicopy suppressors
      that rescue their mitotic-lethal phenotype. None are cell cycle regulators.
      Instead, five encode proteins involved in transcription that bind DNA, modify
      chromatin structure or are regulatory subunits of RNA polymerase II. A sixth
      suppressor, cyclophilin A, is a member of a distinct family of PPIases that are
      targets of immuno suppressive drugs. We show that the expression of some but not
      all genes is decreased in ess1 mutants, and that Ess1 interacts with the C
      terminal domain (CTD) of RNA polymerase II in vitro and in vivo. The results
      forge a strong link between PPIases and the transcription machinery and suggest a
      new model for how Ess1/Pin1 controls mitosis. In this model, Ess1 binds and
      isomerizes the CTD of RNA polymerase II, thus altering its interaction with
      proteins required for transcription of essential cell cycle genes.

PMID- 10899127
TI  - Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3-Rpd3
      histone deacetylase.
AB  - Three families of prolyl isomerases have been identified: cyclophilins, FK506
      binding proteins (FKBPs) and parvulins. All 12 cyclophilins and FKBPs are
      dispensable for growth in yeast, whereas the one parvulin homolog, Ess1, is
      essential. We report here that cyclophilin A becomes essential when Ess1 function
      is compromised. We also show that overexpression of cyclophilin A suppresses ess1
      conditional and null mutations, and that cyclophilin A enzymatic activity is
      required for suppression. These results indicate that cyclophilin A and Ess1
      function in parallel pathways and act on common targets by a mechanism that
      requires prolyl isomerization. Using genetic and biochemical approaches, we found
      that one of these targets is the Sin3-Rpd3 histone deacetylase complex, and that
      cyclophilin A increases and Ess1 decreases disruption of gene silencing by this
      complex. We show that conditions that favor acetylation over deacetylation
      suppress ess1 mutations. Our findings support a model in which Ess1 and
      cyclophilin A modulate the activity of the Sin3-Rpd3 complex, and excess histone
      deacetylation causes mitotic arrest in ess1 mutants.

PMID- 10899128
TI  - The forkhead protein Fkh2 is a component of the yeast cell cycle transcription
      factor SFF.
AB  - In the yeast Saccharomyces cerevisiae, the MADS-box protein Mcm1, which is highly
      related to mammalian SRF (serum response factor), forms a ternary complex with
      SFF (Swi five factor) to regulate the cell cycle expression of genes such as
      SWI5, CLB2 and ACE2. Here we show that the forkhead protein Fkh2 is a component
      of SFF and is essential for ternary complex formation on the SWI5 and ACE2
      promoters. Fkh2 is essential for the correct cell cycle periodicity of SWI5 and
      CLB2 gene expression and is phosphorylated with a timing that is consistent with
      a role in this expression. Furthermore, investigation of the relationship between
      Fkh2 and a related forkhead protein Fkh1 demonstrates that these proteins act in
      overlapping pathways to regulate cell morphology and cell separation. This is the
      first example of a eukaryotic transcription factor complex containing both a MADS
      box and a forkhead protein, and it has important implications for the regulation
      of mammalian gene expression.

PMID- 10899129
TI  - SsrA-mediated tagging and proteolysis of LacI and its role in the regulation of
      lac operon.
AB  - SsrA RNA of Escherichia coli, also known as 10Sa RNA or tmRNA, acts both as tRNA
      and mRNA when ribosomes are paused at the 3' end of an mRNA lacking a stop codon.
      This process, referred to as trans-translation, leads to the addition of a short
      peptide tag to the C-terminus of the incomplete nascent polypeptide. The tagged
      polypeptide is then degraded by C-terminal-specific proteases. Here, we focused
      on endogenous targets for the SsrA system and on a potential regulatory role of
      SsrA RNA. First, we show that trans-translation events occur frequently in
      normally growing E. COLI: cells. More specifically, we report that the lacI mRNA
      encoding Lac repressor (LacI) is a specific natural target for trans-translation.
      The binding of LacI to the lac operators results in truncated lacI mRNAs that
      are, in turn, recognized by the SsrA system. The SsrA-mediated tagging and
      proteolysis of LacI appears to play a role in cellular adaptation to lactose
      availability by supporting a rapid induction of lac operon expression.

PMID- 10899130
TI  - Transcriptional termination and coupled polyadenylation in vitro.
AB  - Using a coupled, in vitro transcription and polyadenylation system we have
      investigated the molecular mechanism of transcriptional termination by RNA
      polymerase II (PolII). We showed previously that specific G-rich sequences pause
      transcription and then activate polyadenylation. We show that physiological pause
      sites activate polyadenylation in our in vitro system. We also investigate the
      mechanism of PolII transcriptional termination, and show that these transcripts
      are either directly released from the transcription complex or are 3' end
      processed while still attached to the complex. We also show that 3' product
      (generated by cleavage/polyadenylation) remains associated with the transcription
      complex, but is rapidly degraded on it.

PMID- 10899131
TI  - Distinct roles of two Yth1p domains in 3'-end cleavage and polyadenylation of
      yeast pre-mRNAs.
AB  - Yth1p is the yeast homologue of the 30 kDa subunit of mammalian cleavage and
      polyadenylation specificity factor (CPSF). The protein is part of the cleavage
      and polyadenylation factor CPF, which includes cleavage factor II (CF II) and
      polyadenylation factor I (PF I), and is required for both steps in pre-mRNA 3'
      end processing. Yth1p is an RNA-binding protein that was previously shown to be
      essential for polyadenylation. Here, we demonstrate that Yth1p is also required
      for the cleavage reaction and that two protein domains have distinct roles in 3'
      end processing. The C-terminal part is required in polyadenylation to tether
      Fip1p and poly(A) polymerase to the rest of CPF. A single point mutation in the
      highly conserved second zinc finger impairs both cleavage and polyadenylation,
      and affects the ability of Yth1p to interact with the pre-mRNA and other CPF
      subunits. Finally, we find that Yth1p binds to CYC1 pre-mRNA in the vicinity of
      the cleavage site. Our results indicate that Yth1p is important for the integrity
      of CPF and participates in the recognition of the cleavage site.

PMID- 10899133
TI  - Uncoupling DNA translocation and helicase activity in PcrA: direct evidence for
      an active mechanism.
AB  - DNA footprinting and nuclease protection studies of PcrA helicase complexed with
      a 3'-tailed DNA duplex reveal a contact region that covers a significant region
      of the substrate both in the presence and absence of a non-hydrolysable analogue
      of ATP, ADPNP. However, details of the interactions of the enzyme with the duplex
      region are altered upon binding of nucleotide. By combining this information with
      that obtained from crystal structures of PcrA complexed with a similar DNA
      substrate, we have designed mutant proteins that are defective in helicase
      activity but that leave the ATPase and single-stranded DNA translocation
      activities intact. These mutants are all located in domains 1B and 2B, which
      interact with the duplex portion of the DNA substrate. Taken together with the
      crystal structures, these data support an 'active' mechanism for PcrA that
      involves two distinct ATP-dependent processes: destabilization of the duplex DNA
      ahead of the enzyme that is coupled to DNA translocation along the single strand
      product.

PMID- 10899132
TI  - Role of ribosome recycling factor (RRF) in translational coupling.
AB  - RNA phage GA coat and lysis protein expression are translationally coupled
      through an overlapping termination and initiation codon UAAUG. Essential for this
      coupling are the proximity of the termination codon of the upstream coat gene to
      the initiation codon of the lysis gene (either a <3 nucleotide separation or
      physical closeness through a possible hairpin structure) but not the Shine
      Dalgarno sequence. This suggests that the ribosomes completing the coat gene
      translation are exclusively responsible for translation of the lysis gene.
      Inactivation of ribosome recycling factor (RRF), which normally releases
      ribosomes at the termination codon, did not influence the expression of the
      reporter gene fused to the lysis gene. This suggests the possibility that RRF may
      not release ribosomes from the junction UAAUG. However, RRF is essential for
      correct ribosomal recognition of the AUG codon as the initiation site for the
      lysis gene.

PMID- 10899134
TI  - Two modes of FEN1 binding to PCNA regulated by DNA.
AB  - The FEN1 nuclease functions during Okazaki fragment maturation in the eukaryotic
      cell. Like many other proliferating cell nuclear antigen (PCNA)-binding proteins,
      FEN1 interacts with the interdomain connector loop (IDCL) of PCNA, and PCNA
      greatly stimulates FEN1 activity. A yeast IDCL mutant pcna-79 (IL126,128AA)
      failed to interact with FEN-1, but, surprisingly, pcna-79 was still very active
      in stimulating FEN1 activity. In contrast, a C-terminal mutant pcna-90
      (PK252,253AA) showed wild-type binding to FEN1 in solution, but poorly stimulated
      FEN1 activity. When PCNA was loaded onto a DNA substrate coupled to magnetic
      beads, it stabilized retention of FEN1 on the DNA. In this DNA-dependent binding
      assay, pcna-79 also stabilized retention of FEN1, but pcna-90 was inactive.
      Therefore, in the absence of DNA, FEN1 interacts with PCNA mainly through the
      IDCL. However, when PCNA encircles the DNA, the C-terminal domain of PCNA rather
      than its IDCL is important for binding FEN1. An FF-->GA mutation in the PCNA
      interaction domain of FEN1 severely decreased both modes of interaction with PCNA
      and resulted in replication and repair defects in vivo.

PMID- 10899135
TI  - Inverted Alu repeats unstable in yeast are excluded from the human genome.
AB  - The nearly one million ALU: repeats in human chromosomes are a potential threat
      to genome integrity. ALU:s form dense clusters where they frequently appear as
      inverted repeats, a sequence motif known to cause DNA rearrangements in model
      organisms. Using a yeast recombination system, we found that inverted ALU: pairs
      can be strong initiators of genetic instability. The highly recombinagenic
      potential of inverted ALU: pairs was dependent on the distance between the
      repeats and the level of sequence divergence. Even inverted ALU:s that were 86%
      homologous could efficiently stimulate recombination when separated by <20 bp.
      This stimulation was independent of mismatch repair. Mutations in the DNA
      metabolic genes RAD27 (FEN1), POL3 (polymerase delta) and MMS19 destabilized
      widely separated and diverged inverted ALU:s. Having defined factors affecting
      inverted ALU: repeat stability in yeast, we analyzed the distribution of ALU:
      pairs in the human genome. Closely spaced, highly homologous inverted ALU:s are
      rare, suggesting that they are unstable in humans. ALU: pairs were identified
      that are potential sites of genetic change.

PMID- 10899137
TI  - Are obese plant genomes on a diet?

PMID- 10899136
TI  - Telomere-led bouquet formation facilitates homologous chromosome pairing and
      restricts ectopic interaction in fission yeast meiosis.
AB  - A polarized chromosomal arrangement with clustered telomeres in a meiotic
      prophase nucleus is often called bouquet and is thought to be important for the
      pairing of homologous chromosomes. Fluorescence in situ hybridization in fission
      yeast indicated that chromosomal loci are positioned in an ordered manner as
      anticipated from the bouquet arrangement. Blocking the formation of the telomere
      cluster with the kms1 mutation created a disorganized chromosomal arrangement,
      not only for the regions proximal to the telomere but also for interstitial
      regions. The kms1 mutation also affected the positioning of a linear
      minichromosome. Consistent with this cytological observation, the frequency of
      ectopic homologous recombination between a linear minichromosome and a normal
      chromosome increased in the kms1 background. Intragenic recombination between
      allelic loci is reduced in the kms1 mutant, but those between non-allelic loci
      are unaffected or slightly increased. Thus, telomere-led chromosome organization
      facilitates homologous pairing and also restricts irregular chromosome pairing
      during meiosis.

PMID- 10899138
TI  - "Spot-on" SNP genotyping.

PMID- 10899139
TI  - Minisatellites: mutability and genome architecture.
AB  - Minisatellites have been found in association with important features of human
      genome biology such as gene regulation, chromosomal fragile sites, and
      imprinting. Our knowledge of minisatellite biology has greatly increased in the
      past 10 years owing to the identification and careful analysis of human
      hypermutable minisatellites, experimental models in yeast, and recent in vitro
      studies of minisatellite recombination properties. In parallel, minisatellites
      have been put forward as potential biomarkers for the monitoring of genotoxic
      agents such as ionizing radiation. We summarize and discuss recent observations
      on minisatellites. In addition we take advantage of recent whole chromosome
      sequence data releases to provide a unifying view which may facilitate the
      annotation of tandem repeat sequences.

PMID- 10899140
TI  - A contiguous 66-kb barley DNA sequence provides evidence for reversible genome
      expansion.
AB  - Organisms with large genomes contain vast amounts of repetitive DNA sequences,
      much of which is composed of retrotransposons. Amplification of retrotransposons
      has been postulated to be a major mechanism increasing genome size and leading to
      "genomic obesity." To gain insights into the relation between retrotransposons
      and genome expansion in a large genome, we have studied a 66-kb contiguous
      sequence at the Rar1 locus of barley in detail. Three genes were identified in
      the 66-kb contig, clustered within an interval of 18 kb. Inspection of sequences
      flanking the gene space unveiled four novel retroelements, designated Nikita,
      Sukkula, Sabrina, and BAGY-2 and several units of the known BARE-1 element. The
      retroelements identified are responsible for at least 15 integration events,
      predominantly arranged as multiple nested insertions. Strikingly, most of the
      retroelements exist as solo LTRs (Long Terminal Repeats), indicating that unequal
      crossing over and/or intrachromosomal recombination between LTRs is a common
      feature in barley. Our data suggest that intraelement recombination events
      deleted most of the original retrotransposon sequences, thereby providing a
      possible mechanism to counteract retroelement-driven genome expansion.

PMID- 10899141
TI  - Eleven densely clustered genes, six of them novel, in 176 kb of mouse t-complex
      DNA.
AB  - Targeted sequencing of the mouse t-complex has started with a 176-kb, gene-rich
      BAC localized with six PCR-based markers in inversion 2/3 of the highly
      duplicated region. The sequence contains 11 genes recovered primarily as cDNAs
      from early embryonic collections, including Igfals (previously placed on
      chromosome 17), Nubp2 (a fully characterized gene), Jsap1 (a JNK-binding
      protein), Rsp29 (the mouse homologue of the rat gene), Ndk3 (a nucleoside
      diphosphate kinase), and six additional putative genes of unknown function. With
      50% GC content, 75% of the DNA transcribed, and one gene/16.0 kb (on average),
      the region may qualify as one of the most gene-dense segments in the mouse genome
      and provides candidates for dosage-sensitive phenotypes and mouse embryonic
      lethals mapped to the vicinity.

PMID- 10899142
TI  - Molecular cloning, genomic organization, developmental regulation, and a knock
      out mutant of a novel leu-rich repeats-containing G protein-coupled receptor
      (DLGR-2) from Drosophila melanogaster.
AB  - After screening the Berkeley Drosophila Genome Project database with sequences
      from a recently characterized Leu-rich repeats-containing G protein-coupled
      receptor (LGR) from Drosophila (DLGR-1), we identified a second gene for a
      different LGR (DLGR-2) and cloned its cDNA. DLGR-2 is 1360 amino acid residues
      long and shows a striking structural homology with members of the glycoprotein
      hormone [thyroid-stimulating hormone (TSH); follicle-stimulating hormone (FSH);
      luteinizing hormone/choriogonadotropin (LH/CG)] receptor family from mammals and
      with two additional, recently identified mammalian orphan LGRs (LGR-4 and LGR-5).
      This homology includes the seven transmembrane region (e.g., 49% amino acid
      identity with the human TSH receptor) and the very large extracellular amino
      terminus. This amino terminus contains 18 Leu-rich repeats-in contrast with the 3
      mammalian glycoprotein hormone receptors and DLGR-1 that contain 9 Leu-rich
      repeats, but resembling the mammalian LGR-4 and LGR-5 that each have 17 Leu-rich
      repeats in their amino termini. The DLGR-2 gene is >18.6 kb pairs long and
      contains 15 exons and 14 introns. Four intron positions coincide with the intron
      positions of the three mammalian glycoprotein hormone receptors and have the same
      intron phasing, showing that DLGR-2 is evolutionarily related to these mammalian
      receptors. The DLGR-2 gene is located at position 34E-F on the left arm of the
      second chromosome and is expressed in embryos and pupae but not in larvae and
      adult flies. Homozygous knock-out mutants, where the DLGR-2 gene is interrupted
      by a P element insertion, die around the time of hatching. This finding, together
      with the expression data, strongly suggests that DLGR-2 is exclusively involved
      in development.

PMID- 10899143
TI  - Characterization and repeat analysis of the compact genome of the freshwater
      pufferfish Tetraodon nigroviridis.
AB  - Tetraodon nigroviridis is a freshwater pufferfish 20-30 million years distant
      from Fugu rubripes. The genome of both tetraodontiforms is compact, mostly
      because intergenic and intronic sequences are reduced in size compared to other
      vertebrate genomes. The previously uncharacterized Tetraodon genome is described
      here together with a detailed analysis of its repeat content and organization. We
      report the sequencing of 46 megabases of bacterial artificial chromosome (BAC)
      end sequences, which represents a random DNA sample equivalent to 13% of the
      genome. The sequence and location of rRNA gene clusters, centromeric and
      subtelocentric satellite sequences have been determined. Minisatellites and
      microsatellites have been cataloged and notable differences were observed in
      comparison with microsatellites from Fugu. The genome contains homologies to all
      known families of transposable elements, including Ty3-gypsy, Ty1-copia, Line
      retrotransposons, DNA transposons, and retroviruses, although their overall
      abundance is <1%. This structural analysis is an important prerequisite to
      sequencing the Tetraodon genome.

PMID- 10899144
TI  - Human and mouse gene structure: comparative analysis and application to exon
      prediction.
AB  - We describe a novel analytical approach to gene recognition based on cross
      species comparison. We first undertook a comparison of orthologous genomic loci
      from human and mouse, studying the extent of similarity in the number, size and
      sequence of exons and introns. We then developed an approach for recognizing
      genes within such orthologous regions by first aligning the regions using an
      iterative global alignment system and then identifying genes based on
      conservation of exonic features at aligned positions in both species. The
      alignment and gene recognition are performed by new programs called and,
      respectively. performed well at exact identification of coding exons in 117
      orthologous pairs tested.

PMID- 10899145
TI  - Reverse transcriptase-polymerase chain reaction validation of 25 "orphan" genes
      from Escherichia coli K-12 MG1655.
AB  - Despite the accumulation of sequence information sampling from a broad spectrum
      of phyla, newly sequenced genomes continue to reveal a high proportion (50%-30%)
      of "uncharacterized" genes, including a significant number of strictly "orphan"
      genes, i.e., putative open reading frames (ORFs) without any resemblance to
      previously determined protein-coding sequences. Most genes found in databases
      have only been predicted by computer methods and have never been experimentally
      validated. Although theoretical evolutionary arguments support the reality of
      genes when homologs are found in a variety of distant species, this is not the
      case for orphan genes. Here, we report the direct reverse transcriptase
      polymerase chain reaction assay of 25 strictly orphan ORFs of Escherichia coli.
      Two growth conditions, exponential and stationary phases, were tested.
      Transcripts were identified for a total of 19 orphan genes, with 2 genes found to
      be expressed in only one of the two growth conditions. Our results suggest that a
      vast majority of E. coli ORFs presently annotated as "hypothetical" correspond to
      bona fide genes. By extension, this implies that randomly occurring "junk" ORFs
      have been actively counter selected during the evolution of the dense E. coli
      genome.

PMID- 10899146
TI  - Microsatellites in different eukaryotic genomes: survey and analysis.
AB  - We examined the abundance of microsatellites with repeated unit lengths of 1-6
      base pairs in several eukaryotic taxonomic groups: primates, rodents, other
      mammals, nonmammalian vertebrates, arthropods, Caenorhabditis elegans, plants,
      yeast, and other fungi. Distribution of simple sequence repeats was compared
      between exons, introns, and intergenic regions. Tri- and hexanucleotide repeats
      prevail in protein-coding exons of all taxa, whereas the dependence of repeat
      abundance on the length of the repeated unit shows a very different pattern as
      well as taxon-specific variation in intergenic regions and introns. Although it
      is known that coding and noncoding regions differ significantly in their
      microsatellite distribution, in addition we could demonstrate characteristic
      differences between intergenic regions and introns. We observed striking relative
      abundance of (CCG)(n)*(CGG)(n) trinucleotide repeats in intergenic regions of all
      vertebrates, in contrast to the almost complete lack of this motif from introns.
      Taxon-specific variation could also be detected in the frequency distributions of
      simple sequence motifs. Our results suggest that strand-slippage theories alone
      are insufficient to explain microsatellite distribution in the genome as a whole.
      Other possible factors contributing to the observed divergence are discussed.

PMID- 10899147
TI  - Rice transposable elements: a survey of 73,000 sequence-tagged-connectors.
AB  - As part of an international effort to sequence the rice genome, the Clemson
      University Genomics Institute is developing a sequence-tagged-connector (STC)
      framework. This framework includes the generation of deep-coverage BAC libraries
      from O. sativa ssp. japonica c.v. Nipponbare and the sequencing of both ends of
      the genomic DNA insert of the BAC clones. Here, we report a survey of the
      transposable elements (TE) in >73,000 STCs. A total of 6848 STCs were found
      homologous to regions of known TE sequences (E<10(-5)) by FASTX search of STCs
      against a set of 1358 TE protein sequences obtained from GenBank. Of these TE
      containing STCs (TE-STCs), 88% (6027) are related to retroelements and the
      remaining are transposase homologs. Nearly all DNA transposons known previously
      in plants were present in the STCs, including maize Ac/Ds, En/Spm, Mutator, and
      mariner-like elements. In addition, 2746 STCs were found to contain regions
      homologous to known miniature inverted-repeat transposable elements (MITEs). The
      distribution of these MITEs in regions near genes was confirmed by EST
      comparisons to MITE-containing STCs, and our results showed that the association
      of MITEs with known EST transcripts varies by MITE type. Unlike the biased
      distribution of retroelements in maize, we found no evidence for the presence of
      gene islands when we correlated TE-STCs with a physical map of the CUGI BAC
      library. These analyses of TEs in nearly 50 Mb of rice genomic DNA provide an
      interesting and informative preview of the rice genome.

PMID- 10899148
TI  - From complete genomes to measures of substitution rate variability within and
      between proteins.
AB  - Accumulation of complete genome sequences of diverse organisms creates new
      possibilities for evolutionary inferences from whole-genome comparisons. In the
      present study, we analyze the distributions of substitution rates among proteins
      encoded in 19 complete genomes (the interprotein rate distribution). To estimate
      these rates, it is necessary to employ another fundamental distribution, that of
      the substitution rates among sites in proteins (the intraprotein distribution).
      Using two independent approaches, we show that intraprotein substitution rate
      variability appears to be significantly greater than generally accepted. This
      yields more realistic estimates of evolutionary distances from amino-acid
      sequences, which is critical for evolutionary-tree construction. We demonstrate
      that the interprotein rate distributions inferred from the genome-to-genome
      comparisons are similar to each other and can be approximated by a single
      distribution with a long exponential shoulder. This suggests that a generalized
      version of the molecular clock hypothesis may be valid on genome scale. We also
      use the scaling parameter of the obtained interprotein rate distribution to
      construct a rooted whole-genome phylogeny. The topology of the resulting tree is
      largely compatible with those of global rRNA-based trees and trees produced by
      other approaches to genome-wide comparison.

PMID- 10899149
TI  - Patterns of variant polyadenylation signal usage in human genes.
AB  - The formation of mature mRNAs in vertebrates involves the cleavage and
      polyadenylation of the pre-mRNA, 10-30 nt downstream of an AAUAAA or AUUAAA
      signal sequence. The extensive cDNA data now available shows that these hexamers
      are not strictly conserved. In order to identify variant polyadenylation signals
      on a large scale, we compared over 8700 human 3' untranslated sequences to
      157,775 polyadenylated expressed sequence tags (ESTs), used as markers of actual
      mRNA 3' ends. About 5600 EST-supported putative mRNA 3' ends were collected and
      analyzed for significant hexameric sequences. Known polyadenylation signals were
      found in only 73% of the 3' fragments. Ten single-base variants of the AAUAAA
      sequence were identified with a highly significant occurrence rate, potentially
      representing 14.9% of the actual polyadenylation signals. Of the mRNAs, 28.6%
      displayed two or more polyadenylation sites. In these mRNAs, the poly(A) sites
      proximal to the coding sequence tend to use variant signals more often, while the
      3'-most site tends to use a canonical signal. The average number of ESTs
      associated with each signal type suggests that variant signals (including the
      common AUUAAA) are processed less efficiently than the canonical signal and could
      therefore be selected for regulatory purposes. However, the position of the site
      in the untranslated region may also play a role in polyadenylation rate.

PMID- 10899150
TI  - Distribution of hammerhead and hammerhead-like RNA motifs through the GenBank.
AB  - Hammerhead ribozymes previously were found in satellite RNAs from plant viroids
      and in repetitive DNA from certain species of newts and schistosomes. To
      determine if this catalytic RNA motif has a wider distribution, we decided to
      scrutinize the GenBank database for RNAs that contain hammerhead or hammerhead
      like motifs. The search shows a widespread distribution of this kind of RNA motif
      in different sequences suggesting that they might have a more general role in RNA
      biology. The frequency of the hammerhead motif is half of that expected from a
      random distribution, but this fact comes from the low CpG representation in
      vertebrate sequences and the bias of the GenBank for those sequences. Intriguing
      motifs include those found in several families of repetitive sequences, in the
      satellite RNA from the carrot red leaf luteovirus, in plant viruses like the
      spinach latent virus and the elm mottle virus, in animal viruses like the
      hepatitis E virus and the caprine encephalitis virus, and in mRNAs such as those
      coding for cytochrome P450 oxidoreductase in the rat and the hamster.

PMID- 10899151
TI  - Parking strategies for genome sequencing.
AB  - The parking strategy is an iterative approach to DNA sequencing. Each iteration
      consists of sequencing a novel portion of target DNA that does not overlap any
      previously sequenced region. Subject to the constraint of no overlap, each new
      region is chosen randomly. A parking strategy is often ideal in the early stages
      of a project for rapidly generating unique data. As a project progresses, parking
      becomes progressively more expensive and eventually prohibitive. We present a
      mathematical model with a generalization to allow for overlaps. This model
      predicts multiple parameters, including progress, costs, and the distribution of
      gap sizes left by a parking strategy. The highly fragmented nature of the gaps
      left after an initial parking strategy may make it difficult to finish a project
      efficiently. Therefore, in addition to our parking model, we model gap closing by
      walking. Our gap-closing model is generalizable to many other strategies. Our
      discussion includes modified parking strategies and hybrids with other
      strategies. A hybrid parking strategy has been employed for portions of the Human
      Genome Project.

PMID- 10899152
TI  - A system for specific, high-throughput genotyping by allele-specific primer
      extension on microarrays.
AB  - This study describes a practical system that allows high-throughput genotyping of
      single nucleotide polymorphisms (SNPs) and detection of mutations by allele
      specific extension on primer arrays. The method relies on the sequence-specific
      extension of two immobilized allele-specific primers that differ at their 3'
      nucleotide defining the alleles, by a reverse transcriptase (RT) enzyme at
      optimized reaction conditions. We show the potential of this simple one-step
      procedure performed on spotted primer arrays of low redundancy by generating over
      8000 genotypes for 40 mutations or SNPs. The genotypes formed three easily
      identifiable clusters and all known genotypes were assigned correctly. Higher
      degrees of multiplexing will be possible with this system as the power of
      discrimination between genotypes remained unaltered in the presence of over 100
      amplicons in a single reaction. The enzyme-assisted reaction provides highly
      specific allele distinction, evidenced by its ability to detect minority sequence
      variants present in 5% of a sample at multiple sites. The assay format based on
      miniaturized reaction chambers at standard 384-well spacing on microscope slides
      carrying arrays with two primers per SNP for 80 samples results in low
      consumption of reagents and makes parallel analysis of a large number of samples
      convenient. In the assay one or two fluorescent nucleotide analogs are used as
      labels, and thus the genotyping results can be interpreted with presently
      available array scanners and software. The general accessibility, simple set-up,
      and the robust procedure of the array-based genotyping system described here will
      offer an easy way to increase the throughput of SNP typing in any molecular
      biology laboratory.

PMID- 10899153
TI  - Interdigitated deletion complexes on mouse chromosome 5 induced by irradiation of
      embryonic stem cells.
AB  - Chromosome deletions have several applications in the genetic analysis of complex
      organisms. They can be used as reagents in region-directed mutagenesis, for
      mapping of simple or complex traits, or to identify biological consequences of
      segmental haploidy, the latter being relevant to human contiguous gene syndromes
      and imprinting. We have generated three deletion complexes in ES (Embryonic Stem)
      cells that collectively span approximately 40 cM of proximal mouse chromosome 5.
      The deletion complexes were produced by irradiation of F(1) hybrid ES cells
      containing herpes simplex virus thymidine kinase genes (tk) integrated at the
      Dpp6, Hdh (Huntington disease locus), or Gabrb1 loci, followed by selection for
      tk-deficient clones. Deletions centered at the adjacent Hdh and Dpp6 loci ranged
      up to approximately 20 cM or more in length and overlapped in an interdigitated
      fashion. However, the interval between Hdh and Gabrb1 appeared to contain a locus
      haploinsufficient for ES cell viability, thereby preventing deletions of either
      complex from overlapping. In some cases, the deletions resolved the order of
      markers that were previously genetically inseparable. A subset of the ES cell
      bearing deletions was injected into blastocysts to generate germline chimeras and
      establish lines of mice segregating the deletion chromosomes. At least 11 of the
      26 lines injected were capable of producing germline chimeras. In general, those
      that failed to undergo germline transmission bore deletions larger than the
      germline-competent clones, suggesting that certain regions of chromosome 5
      contain haploinsufficient developmental genes, and/or that overall embryonic
      viability is cumulatively decreased as more genes are rendered hemizygous. Mice
      bearing deletions presumably spanning the semidominant hammertoe locus (Hm) had
      no phenotype, suggesting that the classic allele is a dominant, gain-of-function
      mutation. Overlapping deletion complexes generated in the fashion described in
      this report will be useful as multipurpose genetic tools and in systematic
      functional mapping of the mouse genome.

PMID- 10899154
TI  - SAGEmap: a public gene expression resource.
AB  - We have constructed a public gene expression data repository and online data
      access and analysis, WWW and FTP sites for serial analysis of gene expression
      (SAGE) data. The WWW and FTP components of this resource, SAGEmap, are located at
      http://www.ncbi.nlm.nih. gov/sage and ftp://ncbi.nlm.nih.gov/pub/sage,
      respectively. We herein describe SAGE data submission procedures, the
      construction and characteristics of SAGE tags to gene assignments, the derivation
      and use of a novel statistical test designed specifically for differential-type
      analyses of SAGE data, and the organization and use of this resource.

PMID- 10899155
TI  - Epsilon protein kinase C in pathological myocardial hypertrophy. Analysis by
      combined transgenic expression of translocation modifiers and Galphaq.
AB  - The epsilon isoform of protein kinase C (PKC) has a critical cardiotrophic
      function in normal postnatal developing heart as demonstrated by cardiac-specific
      transgenic expression of epsilonPKC-selective translocation inhibitor (epsilonV1)
      and activator (psiepsilonRACK) peptides (Mochly-Rosen, D., Wu, G., Hahn, H.,
      Osinska, H., Liron, T., Lorenz, J. N., Robbins, J., and Dorn, G. W., II (2000)
      Circ. Res. 86, 1173-1179). To define the role of epsilonPKC signaling in
      pathological myocardial hypertrophy, epsilonV1 or psiepsilonRACK were co
      expressed in mouse hearts with Galpha(q), a PKC-linked hypertrophy signal
      transducer. Compared with Galpha(q) overexpression alone, co-expression of
      psiepsilonRACK with Galpha(q) increased epsilonPKC particulate partitioning by 30
      +/- 2%, whereas co-expression of epsilonV1 with Galpha(q) reduced particulate
      associated epsilonPKC by 22 +/- 1%. Facilitation of epsilonPKC translocation by
      psiepsilonRACK in Galpha(q) mice improved cardiac contractile function measured
      as left ventricular fractional shortening (30 +/- 3% Galpha(q) versus 43 +/- 2%
      psiepsilonRACK/Galpha(q), p < 0.05). Conversely, inhibition of epsilonPKC by
      epsilonV1 modified the Galpha(q) nonfailing hypertrophy phenotype to that of a
      lethal dilated cardiomyopathy. These opposing effects of epsilonPKC translocation
      activation and inhibition in Galpha(q) hypertrophy indicate that epsilonPKC
      signaling is a compensatory event in myocardial hypertrophy, rather than a
      pathological event, and support the possible therapeutic efficacy of selective
      epsilonPKC translocation enhancement in cardiac insufficiency.

PMID- 10899156
TI  - Characterization of the activation domains of AP-2 family transcription factors.
AB  - Despite sequence variation, all AP-2 isotypes are capable of activating
      transcription, which indicates a functional conservation. We used this property
      to gain a unique insight into the structure and function of the activation motifs
      of AP-2 family transcription factors. We have precisely localized the activation
      motif of human AP-2 alpha to amino acids 52-108. Our experiments indicate that
      similar sequence of amino acids in all AP-2 isotypes except Drosophila AP-2 alpha
      harbor their activation motifs. Within this sequence, fewer than 36 residues are
      critical for transcription activation. Our comparison studies and site-directed
      mutagenic analyses show that these critical amino acids are strategically placed
      within this sequence. These residues are interspersed with nonessential and
      influential residues that vary in composition and length, indicating a structural
      flexibility. The Drosophila AP-2 alpha has its partly conserved activation motif
      in an extended region about twice the length of other AP-2 isotypes. Our results
      reveal essential elements of the amino acid composition of activators in general
      and shed new light on the mechanism of transcription activation.

PMID- 10899157
TI  - A protective role of the low density lipoprotein receptor-related protein against
      amyloid beta-protein toxicity.
AB  - In order to delineate the neuroprotective role of the low density lipoprotein
      receptor-related protein (LRP) against amyloid beta-protein toxicity, studies
      were performed in C6 cells challenged with amyloid beta-protein in the presence
      or absence of activated alpha(2)-macroglobulin. Toxicity was assessed via two
      cell viability assays. We found that this endocytic receptor conferred protection
      against amyloid beta-protein toxicity in the presence of activated alpha(2)
      macroglobulin and its down-regulation via inhibition by receptor-associated
      protein or transfection of cells with presenilin 1, increased susceptibility to
      amyloid beta-protein toxicity. Increased surface LRP immunoreactivity in response
      to amyloid beta-protein challenge was associated with increased translocation of
      LRP from the endoplasmic reticulum to the surface, rather than from increased
      mRNA or protein expression. Furthermore, this translocation of LRP to the surface
      was mediated by a calcium/calmodulin protein kinase II-dependent signaling
      pathway. These studies provide evidence for a protective role of LRP against
      amyloid beta-protein toxicity and may explain the aggressive nature of presenilin
      1 mutation in familial Alzheimer's disease.

PMID- 10899159
TI  - Pemphigus vulgaris antibody identifies pemphaxin. A novel keratinocyte annexin
      like molecule binding acetylcholine.
AB  - Because pemphigus vulgaris (PV) IgGs adsorbed on the rDsg3-Ig-His baculoprotein
      induced blisters in neonatal mice, it was proposed that anti-desmoglein 3 (Dsg 3)
      autoantibody causes PV. However, we found that rDsg3-Ig-His absorbs
      autoantibodies to different antigens, including a non-Dsg 3 keratinocyte protein
      of 130 kDa. This prompted our search for novel targets of PV autoimmunity. The PV
      IgG eluted from a 75-kDa keratinocyte protein band both stained epidermis in a
      pemphigus-like pattern and induced acantholysis in keratinocyte monolayers.
      Screening of a keratinocyte lambdagt11 cDNA library with this antibody identified
      clones carrying cDNA inserts encoding a novel molecule exhibiting approximately
      40% similarity with annexin-2, named pemphaxin (PX). Recombinant PX (rPX-His) was
      produced in Escherichia coli M15 cells, and, because annexins can act as
      cholinergic receptors, its conformation was tested in a cholinergic radioligand
      binding assay. rPX-His specifically bound [(3)H]acetylcholine, suggesting that PX
      is one of the keratinocyte cholinergic receptors known to be targeted by disease
      causing PV antibodies. Preabsorption of PV sera with rPX-His eliminated
      acantholytic activity, and eluted antibody immunoprecipitated native PX. This
      antibody alone did not cause skin blisters in vivo, but its addition to the
      preabsorbed PV IgG fraction restored acantholytic activity, indicating that
      acantholysis in PV results from synergistic action of antibodies to different
      keratinocyte self-antigens, including both acetylcholine receptors and desmosomal
      cadherins.

PMID- 10899158
TI  - Xarvcf, Xenopus member of the p120 catenin subfamily associating with cadherin
      juxtamembrane region.
AB  - The catenin ARVCF is a member of the p120(ctn) subfamily of Armadillo proteins. A
      number of catenins directly bind cadherin cytoplasmic tails, contributing to the
      modulation of cell-cell adhesion and motility processes. Some catenins, such as
      beta-catenin (and likely p120(ctn)), have additional roles within signaling
      pathways regulating gene transcription. We have isolated the Xenopus homolog of
      human ARVCF. Utilizing the cadherin membrane proximal region known to bind
      p120(ctn) and delta-catenin, coimmunoprecipitation experiments demonstrate that
      Xarvcf, likewise, binds cadherin in this region and that corresponding point
      mutations within conserved residues abrogate the Xarvcf-cadherin association.
      Western blot analysis of Xarvcf protein across a series of developmental stages
      reveals changes in protein mobility, likely due to changes in phosphorylation.
      Xarvcf is a maternally provided transcript and expressed in the embryo throughout
      all stages of development. Interestingly, Xarvcf mRNA is differentially spliced
      to produce several isoforms, one of which is developmentally regulated. In common
      with the putative post-translational modifications of the Xarvcf protein, the
      presence of alternative splice isoforms suggests that Xarvcf possesses the
      capacity to effect developmental functions in a regulatable manner.

PMID- 10899160
TI  - Single amino acid mutations in transmembrane domain 5 confer to the plasma
      membrane Ca2+ pump properties typical of the Ca2+ pump of endo(sarco)plasmic
      reticulum.
AB  - Conserved residues in some of the transmembrane domains are proposed to mediate
      ion translocation by P-type pumps. The plasma membrane Ca(2+) pump (PMCA) lacks 2
      of these residues in transmembrane domains (TM) 5 and 8. In particular, a
      glutamic acid (Glu-771) residue in TM5, which is proposed to be involved in the
      binding and transport of Ca(2+) by the sarcoplasmic reticulum Ca(2+) pump
      (SERCA), is replaced by an alanine (Ala-854) in the PMCA pump. Ala-854 has been
      mutated to Glu, Asp, or Gln; Glu-975 in TM8, which is an Ala in the SERCA pump,
      has been mutated to Gln, Asp, or Ala. The mutants have been expressed in three
      cell systems, with or without the help of viruses. When expressed in large
      amounts in Sf9 cells, the mutated pumps were isolated and analyzed in the
      purified state. Two of the three TM8 mutants were correctly delivered to the
      plasma membrane and were active. All the TM5 mutants were retained in the
      endoplasmic reticulum; two of them (A854Q and A854E) retained activity. Their
      properties (La(3+) sensitivity and decay of the phosphorylated intermediate,
      higher cooperativity of Ca(2+) binding with a Hill's coefficient approaching 2)
      differed from those of the expressed wild type PMCA pump, and resembled those of
      the SERCA pump.

PMID- 10899161
TI  - Doxorubicin-induced apoptosis in endothelial cells and cardiomyocytes is
      ameliorated by nitrone spin traps and ebselen. Role of reactive oxygen and
      nitrogen species.
AB  - Doxorubicin (DOX) is a broad spectrum anthracycline antibiotic used to treat a
      variety of cancers. Redox activation of DOX to form reactive oxygen species has
      been implicated in DOX-induced cardiotoxicity. In this work we investigated DOX
      induced apoptosis in cultured bovine aortic endothelial cells and cardiomyocytes
      isolated from adult rat heart. Exposure of bovine aortic endothelial cells or
      myocytes to submicromolar levels of DOX induced significant apoptosis as measured
      by DNA fragmentation and terminal deoxynucleotidyltransferase-mediated nick-end
      labeling assays. Pretreatment of cells with 100 microm nitrone spin traps, N-tert
      butyl-alpha-phenylnitrone (PBN) or alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone
      (POBN) dramatically inhibited DOX-induced apoptosis. Ebselen (20-50 microm), a
      glutathione peroxidase mimetic, also significantly inhibited apoptosis. DOX (0.5
      1 microm) inactivated mitochondrial complex I by a superoxide-dependent
      mechanism. PBN (100 microm), POBN (100 microm), and ebselen (50 microm) restored
      complex I activity. These compounds also inhibited DOX-induced caspase-3
      activation and cytochrome c release. PBN and ebselen also restored glutathione
      levels in DOX-treated cells. We conclude that nitrone spin traps and ebselen
      inhibit the DOX-induced apoptotic signaling mechanism and that this antiapoptotic
      mechanism may be linked in part to the inhibition in formation or scavenging of
      hydrogen peroxide. Therapeutic strategies to mitigate DOX cardiotoxicity should
      be reexamined in light of these emerging antiapoptotic mechanisms of
      antioxidants.

PMID- 10899162
TI  - Unusual location of a mitochondrial gene. Subunit III of cytochrome C oxidase is
      encoded in the nucleus of Chlamydomonad algae.
AB  - The algae of the family Chlamydomonadaceae lack the gene cox3 that encodes
      subunit III of cytochrome c oxidase in their mitochondrial genomes. This
      observation has raised the question of whether this subunit is present in
      cytochrome c oxidase or whether the corresponding gene is located in the nucleus.
      Cytochrome c oxidase was isolated from the colorless chlamydomonad Polytomella
      spp., and the existence of subunit III was established by immunoblotting analysis
      with an antibody directed against Saccharomyces cerevisiae subunit III. Based
      partly upon the N-terminal sequence of this subunit, oligodeoxynucleotides were
      designed and used for polymerase chain reaction amplification, and the resulting
      product was used to screen a cDNA library of Chlamydomonas reinhardtii. The
      complete sequences of the cox3 cDNAs from Polytomella spp. and C. reinhardtii are
      reported. Evidence is provided that the genes for cox3 are encoded by nuclear
      DNA, and the predicted polypeptides exhibit diminished physical constraints for
      import as compared with mitochondrial-DNA encoded homologs. This indicates that
      transfer of this gene to the nucleus occurred before Polytomella diverged from
      the photosynthetic Chlamydomonas lineage and that this transfer may have occurred
      in all chlamydomonad algae.

PMID- 10899163
TI  - Isoform-specific differences between the type Ialpha and IIalpha cyclic AMP
      dependent protein kinase anchoring domains revealed by solution NMR.
AB  - Cyclic AMP dependent protein kinase (PKA) is controlled, in part, by the
      subcellular localization of the enzyme (). Discovery of dual specificity
      anchoring proteins (d-AKAPs) indicates that not only is the type II, but also the
      type I, enzyme localized (). It appears that the type I enzyme is localized in a
      novel, dynamic fashion as opposed to the apparent static localization of the type
      II enzyme. Recently, the structure of the dimerization/docking (D/D) domain from
      the type II enzyme was solved (). This work revealed an X-type four-helix bundle
      motif with a hydrophobic patch that modulates AKAP interactions. To understand
      the dynamic versus static localization of PKA, multidimensional NMR techniques
      were used to investigate the structural features of the type I D/D domain. Our
      results indicate a conserved helix-turn-helix motif in the type I and type II D/D
      domains. However, important differences between the two domains are evident in
      the extreme NH(2) terminus: this region is extended in the type II domain,
      whereas it is helical in the type I protein. The NH(2)-terminal residues in
      RIIalpha contain determinants for anchoring, and the orientation and packing of
      this helical element in the RIalpha structure may have profound consequences in
      the recognition surface presented to the AKAPs.

PMID- 10899164
TI  - Clustering of mutations in the first transmembrane domain of the human reduced
      folate carrier in GW1843U89-resistant leukemia cells with impaired antifolate
      transport and augmented folate uptake.
AB  - We have studied the molecular basis for the resistance of human CEM leukemia
      cells to GW1843, a thymidylate synthase inhibitor. GW1843-resistant cells
      displayed a approximately 100-fold resistance to GW1843 and methotrexate but were
      collaterally sensitive to the lipophilic antifolates trimetrexate and AG337,
      which enter cells by diffusion. These cells exhibited a 12-fold decreased
      methotrexate influx but surprisingly had a 2-fold decreased folic acid growth
      requirement. This was associated with a 4-fold increased influx of folic acid, a
      3.5-fold increased steady-state level of folic acid, and a 2.3-fold expansion of
      the cellular folate pool. Characterization of the transport kinetic properties
      revealed that GW1843-resistant cells had the following alterations: (a) 11-fold
      decreased transport K(m) for folic acid; (b) 6-fold increased transport K(m) for
      GW1843; and (c) a slightly increased transport V(max) for folic acid. Sequence
      analysis showed that GW1843-resistant cells contained the mutations Val-29 -->
      Leu, Glu-45 --> Lys, and Ser-46 --> Ile in the first transmembrane domain of the
      reduced folate carrier. Transfection of the mutant-reduced folate carrier cDNA
      into methotrexate transport null cells conferred resistance to GW1843. This is
      the first demonstration of multiple mutations in a confined region of the human
      reduced folate carrier in an antifolate-resistant mutant. We conclude that
      certain amino acid residues in the first transmembrane domain play a key role in
      (anti)folate binding and in the conferring of drug resistance.

PMID- 10899165
TI  - Transcription factor ZBP-89 cooperates with histone acetyltransferase p300 during
      butyrate activation of p21waf1 transcription in human cells.
AB  - Inducible p53-independent regulation of the cyclin-dependent kinase inhibitor
      p21(waf1) transcription is mediated through proximal GC-rich sites. Prior studies
      have shown that Sp1, Sp3, and the histone acetylase co-activator p300 are
      components of the complexes binding to these sites. Although Sp1 and Sp3
      collaborate with p300, a direct interaction between Sp1 and p300 does not occur.
      This study sought to determine whether ZBP-89 rather than Sp1 is the direct
      target of p300 during butyrate induction of p21(waf1). ZBP-89 (BFCOL1, BERF-1,
      ZNF 148) is a Kruppel-type zinc finger transcription factor that binds to GC-rich
      elements and represses or activates known target genes. Adenoviral-mediated
      expression of ZBP-89 in HT-29 cells revealed that ZBP-89 potentiates butyrate
      induction of endogenous p21(waf1) gene expression. Further, cotransfection of a
      ZBP-89 expression vector with a 2.3-kilobase p21(waf1) reporter recapitulated the
      potentiation by butyrate. DNase I footprinting analysis of the human p21(waf1)
      promoter with recombinant ZBP-89 identified a binding site at -245 to -215.
      Electrophoretic mobility shift assays confirmed that both recombinant and
      endogenous ZBP-89 and Sp1 bind to this element. The potentiation was abolished in
      the presence of adenoviral protein E1A. Deletion of the N-terminal domain of ZBP
      89 abolished the potentiation mediated by butyrate treatment. This same deletion
      mutant abolished the ZBP-89 interaction with p300. Cotransfection of p300 with
      ZBP-89 stimulated the p21(waf1) promoter in the absence of butyrate. p300 co
      precipitated with ZBP-89 but not with Sp1, whereas ZBP-89 co-precipitated with
      Sp1. Together, these findings demonstrate that ZBP-89 also plays a critical role
      in butyrate activation of the p21(waf1) promoter and reveals preferential
      cooperation of this four-zinc finger transcription factor with p300.

PMID- 10899166
TI  - Identification and characterization of two neuromedin U receptors differentially
      expressed in peripheral tissues and the central nervous system.
AB  - Two structurally related, G-protein-coupled receptors were identified as
      receptors for the neuropeptide, neuromedin U. This peptide is found in highest
      levels in the gut and genitourinary system where it potently contracts smooth
      muscle but is also expressed in the spinal cord and discrete regions of the
      brain. Binding sites for neuromedin U have been characterized in rat uterus,
      however, little is known about the activity of this peptide in the regions of the
      central nervous system where it is expressed. The receptors characterized in this
      report are activated by neuromedin U at nanomolar potency in heterologous
      expression systems and bind radiolabeled neuromedin U with high affinity.
      Localization of the receptor RNA by quantitative reverse transcription-polymerase
      chain reaction in a variety of human tissues shows distinct expression patterns
      for the two receptors. NMU1 is expressed predominantly in peripheral tissues,
      whereas NMU2 is more highly expressed in the central nervous system.
      Identification of neuromedin U receptor subtypes will greatly aid in the
      determination of the physiological roles of this peptide.

PMID- 10899167
TI  - Bradykinin-regulated interactions of the mitogen-activated protein kinase pathway
      with the endothelial nitric-oxide synthase.
AB  - Activation of the bradykinin B2 receptor in endothelial cells initiates a complex
      array of cellular responses mediated by diverse signaling pathways, including
      stimulation of the mitogen-activated protein (MAP) kinase cascade and activation
      of the endothelial isoform of nitric-oxide synthase (eNOS). Several protein
      kinases have been implicated in eNOS regulation, but the role of MAP kinases
      remains less well understood. We explored the interactions between eNOS and
      components of the MAP kinase pathway in bovine aortic endothelial cells (BAEC).
      Using co-immunoprecipitation experiments, we isolated eNOS in a complex with the
      MAP kinases extracellular signal-regulated kinases 1 and 2 (ERK1/2) as well as
      the protein kinases Raf-1 and Akt. Within minutes of adding bradykinin to BAEC,
      the eNOS-Raf-1-ERK-Akt heteromeric complex dissociated, and it subsequently
      reassociated following more prolonged agonist stimulation. Bradykinin treatment
      of BAEC led to the activation of ERK, associated with an increase in
      phosphorylation of eNOS; phosphorylation of eNOS by ERK in vitro significantly
      reduced eNOS enzyme activity. Evidence for the direct phosphorylation of eNOS by
      MAP kinase in BAEC came from "back-phosphorylation" experiments using [gamma
      (32)P]ATP and ERK in vitro to phosphorylate eNOS isolated from cells previously
      treated with bradykinin or the MAP kinase inhibitor PD98059. The ERK-catalyzed in
      vitro (32)P phosphorylation of eNOS isolated from BAEC treated with bradykinin
      was significantly attenuated compared with untreated cells, indicating that
      bradykinin treatment led to the phosphorylation of ERK-sensitive sites in cells.
      Conversely, eNOS isolated from endothelial cells pretreated with the MAP kinase
      inhibitor PD98059 showed increased ERK-promoted phosphorylation in vitro. Taken
      together, our results suggest that bradykinin-induced activation of ERK leads to
      eNOS phosphorylation and enzyme inhibition, a process influenced by the
      reversible associations of members of the MAP kinase pathway with eNOS.

PMID- 10899168
TI  - ATP and ADP modulate a cation channel formed by Hsc70 in acidic phospholipid
      membranes.
AB  - Heat shock proteins are molecular chaperones that participate in different
      cellular processes, particularly the folding and translocation of polypeptides
      across membranes. In this regard, members of the Hsp70 family of heat shock
      proteins have been observed in close proximity to cellular membranes. In this
      study, the direct interaction between Hsc70, which is constitutively expressed in
      cells, and lipid membranes was investigated. Recombinant Hsc70 was incorporated
      into artificial lipid bilayers, and a transmembrane ion flow was detected,
      suggesting the incorporation of an ion pathway. This ion flow was very stable and
      occurred in well defined, multilevel discrete electrical current events,
      indicating the formation of a multiconductance ion channel. The Hsc70 channel
      activity is ATP-dependent and is reversibly blocked by ADP. This channel has
      cationic selectivity. Thus, Hsc70 can directly interact with lipid membranes to
      create functionally stable ATP-dependent cationic pathways.

PMID- 10899169
TI  - NFkappa B interacts with serum amyloid A3 enhancer factor to synergistically
      activate mouse serum amyloid A3 gene transcription.
AB  - We had previously identified a distal regulatory element (DRE) in the mouse serum
      amyloid A3 (SAA3) promoter that functions as a cytokine-inducible transcription
      enhancer. Within this DRE, three functional elements interact with CCAAT/enhancer
      binding protein (C/EBP) and SAA3 enhancer factor (SEF) transcription factors. In
      this study, we show that cotransfection of the SEF expression plasmid with an
      SAA3/luciferase reporter resulted in 3-5-fold activation of the SAA3 promoter.
      When SEF-transfected cells were further stimulated with conditioned medium or
      interleukin-1, SAA3 promoter activity was dramatically increased, suggesting that
      SEF may cooperate functionally with other interleukin-1-inducible transcription
      factors to synergistically up-regulate SAA3 gene transcription. Indeed,
      cotransfection of SEF and NFkappaBp65 expression DNAs resulted in synergistic
      activation of the SAA3 promoter. Intriguingly, no consensus NFkappaB-binding site
      was found in the SAA3 promoter region; rather a putative NFkappaB-binding
      sequence with 3-base pair mismatches was identified in the DRE. When this
      sequence was used in an electrophoretic mobility shift assay, it interacted with
      NFkappaBp50, albeit with binding affinities that were several hundredfold lower
      than that with the consensus NFkappaB probe. Functional cooperation between SEF
      and NFkappaB was further strengthened by the finding that SEF and NFkappaB formed
      stable cytokine-inducible protein-protein complexes. Finally, despite its weak
      binding, mutation of this NFkappaB-binding site nevertheless dramatically reduced
      both NFkappaBp65- and cytokine-mediated induction of SAA3 promoter. Therefore,
      the molecular basis for the functional synergy between SEF and NFkappaB may, in
      part, be the ability of SEF to recruit NFkappaB through physical interactions
      that lead to enhancement or stabilization of NFkappaB binding to the SAA3
      promoter element.

PMID- 10899170
TI  - Evidence for a common step in three different processes for modulating the
      kinetic properties of glucocorticoid receptor-induced gene transcription.
AB  - The dose-response curve of steroid hormones and the associated EC(50) value are
      critical parameters both in the development of new pharmacologically active
      compounds and in the endocrine therapy of various disease states. We have
      recently described three different variables that can reposition the dose
      response curve of agonist-bound glucocorticoid receptors (GRs): a 21-base pair
      sequence of the rat tyrosine aminotransferase gene called a glucocorticoid
      modulatory element (GME), GR concentration, and coactivator concentration. At the
      same time, each of these three components was found to influence the partial
      agonist activity of antiglucocorticoids. In an effort to determine whether these
      three processes proceed via independent pathways or a common intermediate, we
      have examined several mechanistic details. The effects of increasing
      concentrations of both GR and the coactivator TIF2 are found to be saturable.
      Furthermore, saturating levels of either GR or TIF2 inhibit the ability of each
      protein, and the GME, to affect further changes in the dose-response curve or
      partial agonist activity of antisteroids. This competitive inhibition suggests
      that all three modulators proceed through a common step involving a titratable
      factor. Support for this hypothesis comes from the observation that a fragment of
      the coactivator TIF2 retaining intrinsic transactivation activity is a dominant
      negative inhibitor of each component (GME, GR, and coactivator). This inhibition
      was not due to nonspecific effects on the general transcription machinery as the
      VP16 transactivation domain was inactive. The viral protein E1A also prevented
      the action of each of the three components in a manner that was independent of
      E1A's ability to block the histone acetyltransferase activity of CBP.
      Collectively, these results suggest that three different inputs (GME, GR, and
      coactivator) for perturbing the dose-response curve, and partial agonist
      activity, of GR-steroid complexes act by converging at a single step that
      involves a limiting factor prior to transcription initiation.

PMID- 10899171
TI  - The biosynthesis of hepatic cholesterol esters and triglycerides is impaired in
      mice with a disruption of the gene for stearoyl-CoA desaturase 1.
AB  - Stearoyl-CoA desaturase (SCD) is a microsomal enzyme required for the
      biosynthesis of oleate and palmitoleate, which are the major monounsaturated
      fatty acids of membrane phospholipids, triglycerides, and cholesterol esters. Two
      well characterized isoforms of SCD, SCD1 and SCD2, exist in the mouse. Most mouse
      tissues express SCD1 and 2 with the exception of the liver, which expresses
      mainly the SCD1 isoform. We found that asebia mice homozygous for a natural
      mutation of the gene for SCD1 (SCD-/-) are deficient in hepatic cholesterol
      esters and triglycerides despite the presence of normal activities of acyl
      CoA:cholesterol acyltransferase and glycerol phosphate acyltransferase, the
      enzymes responsible for cholesterol ester and triglyceride synthesis,
      respectively, in the liver of these mice. Feeding diets supplemented with
      triolein or tripalmitolein to the SCD-/- mice resulted in an increase in the
      levels of 16:1 and 18:1 in the liver but failed to restore the 18:1 and 16:1
      levels of the cholesterol ester and triglycerides to the levels found in normal
      mice. The SCD-/- mouse had very low levels of triglycerides in the VLDL and LDL
      lipoprotein fractions compared with the normal animal. Transient transfection of
      an SCD1 expression vector into Chinese hamster ovary cells resulted in increased
      SCD activity and esterification of cholesterol to cholesterol esters. Taken
      together, our observations demonstrate that the oleoyl-CoA and palmitoleyl-CoA
      produced by SCD1 are necessary to synthesize enough cholesterol esters and
      triglycerides in the liver and suggest that regulation of SCD1 activity plays an
      important role in mechanisms of cellular cholesterol homeostasis.

PMID- 10899172
TI  - Specificity of the binding of synapsin I to Src homology 3 domains.
AB  - Synapsins are synaptic vesicle-associated phosphoproteins involved in synapse
      formation and regulation of neurotransmitter release. Recently, synapsin I has
      been found to bind the Src homology 3 (SH3) domains of Grb2 and c-Src. In this
      work we have analyzed the interactions between synapsins and an array of SH3
      domains belonging to proteins involved in signal transduction, cytoskeleton
      assembly, or endocytosis. The binding of synapsin I was specific for a subset of
      SH3 domains. The highest binding was observed with SH3 domains of c-Src,
      phospholipase C-gamma, p85 subunit of phosphatidylinositol 3-kinase, full-length
      and NH(2)-terminal Grb2, whereas binding was moderate with the SH3 domains of
      amphiphysins I/II, Crk, alpha-spectrin, and NADPH oxidase factor p47(phox) and
      negligible with the SH3 domains of p21(ras) GTPase-activating protein and COOH
      terminal Grb2. Distinct sites in the proline-rich COOH-terminal region of
      synapsin I were found to be involved in binding to the various SH3 domains.
      Synapsin II also interacted with SH3 domains with a partly distinct binding
      pattern. Phosphorylation of synapsin I in the COOH-terminal region by
      Ca(2+)/calmodulin-dependent protein kinase II or mitogen-activated protein kinase
      modulated the binding to the SH3 domains of amphiphysins I/II, Crk, and alpha
      spectrin without affecting the high affinity interactions. The SH3-mediated
      interaction of synapsin I with amphiphysins affected the ability of synapsin I to
      interact with actin and synaptic vesicles, and pools of synapsin I and
      amphiphysin I were shown to associate in isolated nerve terminals. The ability to
      bind multiple SH3 domains further implicates the synapsins in signal transduction
      and protein-protein interactions at the nerve terminal level.

PMID- 10899173
TI  - The focal adhesion kinase suppresses transformation-associated, anchorage
      independent apoptosis in human breast cancer cells. Involvement of death receptor
      related signaling pathways.
AB  - The focal adhesion kinase (FAK) is a mediator of cell-extracellular matrix
      signaling events and is overexpressed in tumor cells. In order to rapidly down
      regulate FAK function in normal and transformed mammary cells, we have used
      adenoviral gene transduction of the carboxyl-terminal domain of FAK (FAK-CD).
      Transduction of adenovirus containing FAK-CD in breast cancer cells caused loss
      of adhesion, degradation of p125(FAK), and induced apoptosis. Furthermore, breast
      tumor cells that were viable without matrix attachment also underwent apoptosis
      upon interruption of FAK function, demonstrating that FAK is a survival signal in
      breast tumor cells even in the absence of matrix signaling. In addition, both
      anchorage-dependent and anchorage-independent apoptotic signaling required Fas
      associated death domain and caspase-8, suggesting that a death receptor-mediated
      apoptotic pathway is involved. Finally, FAK-CD had no effect on adhesion or
      viability in normal mammary cells, despite the loss of tyrosine phosphorylation
      of p125(FAK). These results indicate that FAK-mediated signaling is required for
      both cell adhesion and anchorage-independent survival and the disruption of FAK
      function involves the Fas-associated death domain and caspase-8 apoptotic
      pathway.

PMID- 10899174
TI  - Fractalkine cleavage from neuronal membranes represents an acute event in the
      inflammatory response to excitotoxic brain damage.
AB  - Fractalkine is a recently identified chemokine that exhibits cell adhesion and
      chemoattractive properties. It represents a unique member of the chemokine
      superfamily because it is located predominantly in the brain in which it is
      expressed constitutively on specific subsets of neurons. To elucidate the
      possible role of neuronally expressed fractalkine in the inflammatory response to
      neuronal injury, we have analyzed the regulation of fractalkine mRNA expression
      and protein cleavage under conditions of neurotoxicity. We observed that mRNA
      encoding fractalkine is unaffected by experimental ischemic stroke (permanent
      middle cerebral artery occlusion) in the rat. Similarly, in vitro, levels of
      fractalkine mRNA were unaffected by ensuing excitotoxicity. However, when
      analyzed at the protein level, we found that fractalkine is rapidly cleaved from
      cultured neurons in response to an excitotoxic stimulus. More specifically,
      fractalkine cleavage preceded actual neuronal death by 2-3 hr, and, when
      evaluated functionally, fractalkine represented the principal chemokine released
      from the neurons into the culture medium upon an excitotoxic stimulus to promote
      chemotaxis of primary microglial and monocytic cells. We further demonstrate that
      cleavage of neuron-derived, chemoattractive fractalkine can be prevented by
      inhibition of matrix metalloproteases. These data strongly suggest that dynamic
      proteolytic cleavage of fractalkine from neuronal membranes in response to a
      neurotoxic insult, and subsequent chemoattraction of reactive immune cells, may
      represent an early event in the inflammatory response to neuronal injury.

PMID- 10899175
TI  - Laminar specificity of local circuits in barrel cortex of ephrin-A5 knockout
      mice.
AB  - Cortical circuits are characterized by layer-specific axonal arbors. Molecular
      laminar cues are believed to direct the development of this specificity. We have
      tested the hypothesis that ephrin-A5 is responsible for preventing layer 2/3
      pyramidal cell axons from branching within layer 4 (Castellani et al., 1998) by
      assessing the laminar specificity of axonal arbors in ephrin-A5 knockout mice. We
      find that in barrel cortex of knockout mice, layer 2/3 pyramidal neurons form
      axonal arbors specifically in layers 2/3 and 5, avoiding layer 4. This pattern of
      arborization is indistinguishable from that of wild-type littermates.
      Furthermore, we find that in wild-type mice, laminar patterns of ephrin-A5
      expression differ between cortical areas despite the similarity of layer-specific
      local cortical circuits across areas. Most notably, ephrin-A5 is not expressed
      preferentially in layer 4 of wild-type mouse barrel cortex. We conclude that
      ephrin-A5 is not responsible for preventing the development of layer 2/3
      pyramidal cell axonal arbors in layer 4 of mouse barrel cortex. These
      observations also suggest that if ephrin-A5 plays a role in the emergence of
      layer-specific circuits, that role must differ between cortical areas.

PMID- 10899176
TI  - Glutamate transmission in the nucleus accumbens mediates relapse in cocaine
      addiction.
AB  - Elevated dopamine transmission in the nucleus accumbens is thought to be a
      primary mediator of addiction to cocaine. However, repeated exposure to cocaine
      is associated with the recruitment of glutamate transmission. This poses the
      possibility that the behaviors characterizing cocaine addiction, such as craving
      induced relapse, may not be preferentially mediated by dopamine transmission. An
      animal model of relapse was used to demonstrate that glutamate, and not dopamine
      transmission in the nucleus accumbens, is a primary mediator of cocaine-induced
      reinstatement of drug-seeking behavior. Reinstatement was produced by a systemic
      injection of cocaine or by the microinjection of the glutamate receptor agonist
      AMPA or dopamine into the nucleus accumbens. It was found that microinjection of
      an AMPA receptor antagonist into the nucleus accumbens blocked reinstatement by
      all compounds, whereas a dopamine receptor antagonist was effective only in
      blocking reinstatement by intra-accumbens dopamine administration. These data
      suggest an important role for nucleus accumbens glutamate and not dopamine
      transmission in cocaine-induced relapse to drug-seeking behavior.

PMID- 10899177
TI  - Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in
      rats: involvement of heteromeric P2X2/3 receptor signaling in capsaicin
      insensitive primary afferent neurons.
AB  - Extracellular ATP has been known to activate sensory neurons via the ATP-gated
      ion channels P2X receptors, indicating that the P2X receptors may play a role in
      signal transduction of pain from the periphery to the spinal cord in vivo. Here,
      we found a novel nociceptive response induced by ATP, mechanical allodynia
      (hypersensitivity to innocuous mechanical stimulus). Injection of alpha,beta
      methylene ATP (alpha(beta)meATP), an agonist to P2X receptor, into plantar
      surface in rats produced the mechanical allodynia along with previously described
      nocifensive behavior and thermal hyperalgesia. This allodynic response was
      blocked by pretreatment with the P2 receptor antagonist pyridoxal-phosphate-6
      azophenyl-2',4'-disulfonate. Interestingly, only the mechanical allodynia evoked
      by alpha(beta)meATP selectively remained in neonatal capsaicin-treated adult rats
      that had selectively lost the capsaicin-sensitive neurons. ATP has been shown to
      produce two distinguishable electrophysiological responses (inward currents with
      rapid and slow desensitization) in dorsal root ganglion (DRG) neurons. In the
      present electrophysiological experiment, the percentage of DRG neurons that
      responded to alpha(beta)meATP with slow desensitizing inward current remained
      constant in capsaicin-treated rats, whereas the percentage that responded with
      rapid desensitizing current dramatically decreased. Taken together with our
      previous finding that the alpha(beta)meATP-activated slow desensitizing current
      in DRG neurons is mediated by heteromeric P2X2/3 (P2X2 and P2X3) receptors, it is
      hypothesized that activation of heteromeric P2X2/3 receptors in peripheral
      terminals of capsaicin-insensitive primary afferent fibers leads to the induction
      of mechanical allodynia.

PMID- 10899178
TI  - On the mechanism of desensitization in quisqualate-type glutamate channels.
AB  - Desensitization of crayfish glutamate channels was studied in outside-out patches
      employing an improved fast drug-application technique. Low concentrations of
      glutamate produced substantial desensitization without correlation with the
      detected number of open channels. The desensitization time constant (tau(D)) was
      found to be independent of glutamate concentration (0.3-20 mM). These results
      suggest that in addition to desensitization from a state of fully liganded
      channels, a substantial fraction of desensitization occurs also from channels in
      a partly-liganded state. A kinetic model was developed. The model accounts for
      the multifaceted behavior of desensitization as well as for resensitization.

PMID- 10899179
TI  - Properties of the internal representation of gravity inferred from spatial
      direction and body-tilt estimates.
AB  - One of the key questions in spatial perception is whether the brain has a common
      representation of gravity that is generally accessible for various perceptual
      orientation tasks. To evaluate this idea, we compared the ability of six tilted
      subjects to indicate earth-centric directions in the dark with a visual and an
      oculomotor paradigm and to estimate their body tilt relative to gravity.
      Subjective earth-horizontal and -vertical data were collected, either by
      adjusting a visual line or by making saccades, at 37 roll-tilt angles across the
      entire range. These spatial perception responses and the associated body-tilt
      estimates were subjected to a principal-component analysis to describe their tilt
      dependence. This analysis allowed us to separate systematic and random errors in
      performance, to disentangle the effects of task (horizontal vs. vertical) and
      paradigm (visual vs. oculomotor) in the space-perception data, and to compare the
      veridicality of space perception and the sense of self-tilt. In all spatial
      orientation tests, whether involving space-perception or body-tilt judgments,
      subjects made considerable systematic errors which mostly betrayed tilt
      underestimation [Aubert effect (A effect)] and peaked near 130 degrees tilt.
      However, the A effect was much smaller in body-tilt estimates than in spatial
      pointing, implying that the underlying signal processing must have been
      different. Pointing results obtained with the visual and the oculomotor paradigm
      were not identical either, but these differences, which were task-related
      (horizontal vs. vertical), were subtle in comparison. The tilt-dependent pattern
      of random errors (noisy scatter) was almost identical in visual and oculomotor
      pointing results, showing a steep monotonic increase with tilt angle, but was
      again clearly different in the body-tilt estimates. These findings are discussed
      in the context of a conceptual model in an attempt to explain how the different
      patterns of systematic and random errors in external-space and self-tilt
      perception may come about. The scheme proposes that basically similar
      computational mechanisms, working with different settings, may be responsible.

PMID- 10899180
TI  - Distribution of functional glutamate and GABA receptors on hippocampal pyramidal
      cells and interneurons.
AB  - The distribution of functional neurotransmitter receptors is an important
      determinant of neuronal information processing. To map the location of functional
      glutamate and GABA receptors on individual hippocampal neurons, we photolyzed
      "caged" glutamate and GABA while measuring the electrical currents resulting from
      activation of these receptors. Responses to uncaged neurotransmitters were
      spatially nonuniform and varied according to the type of receptor and type of
      neuron. Every region of CA1 pyramidal cells responded to glutamate and GABA, but
      glutamate and GABA receptors increased in density along the length of their
      distal dendrites. Similar gradients of glutamate receptors were found in stratum
      radiatum interneurons, while GABA responses were detectable only in the
      perisomatic region of these interneurons. These regional variations in receptor
      distribution indicate the selective targeting of receptors on central neurons and
      may reflect a mechanism for local regulation of synaptic efficacy.

PMID- 10899181
TI  - Functional role of NMDA autoreceptors in olfactory mitral cells.
AB  - The output of the olfactory bulb is governed by the interaction of synaptic
      potentials with the intrinsic conductances of mitral cells. While mitral cells
      often are considered as simple relay neurons, conveying activity in olfactory
      receptor cells to the piriform cortex, there is strong physiological and
      behavioral evidence that local synaptic interactions within the olfactory bulb
      modulate mitral cell discharges and facilitate odorant discrimination.
      Understanding the circuitry of the olfactory bulb is complicated by the fact that
      most dendrites in this region are both pre- and postsynaptic. Feedback inhibition
      is mediated through reciprocal dendrodendritic synapses between the secondary
      dendrites of mitral cells and GABAergic granule cells. Here we show that
      glutamate released from mitral cell dendrites also activates local N-methyl-D
      aspartate (NMDA) autoreceptors, generating an inward tail current following
      depolarizing voltage steps. Autoreceptor-mediated self-excitation is calcium
      dependent, can be evoked by single action potentials in the presence of
      magnesium, and is graded with the number of spikes in a train. We find that
      dendrodendritic inhibition also is evoked by single action potentials but
      saturates rapidly during repetitive discharges. Self-excitation also underlies
      the prolonged afterdischarges apparent in mitral cells following potassium
      channel blockade. Both afterdischarges and autoreceptor-mediated tail currents
      persist in TTX, suggesting that they are produced by local rather than
      polysynaptic actions of glutamate. Blockade of NMDA autoreceptors with 2-amino-5
      phosphonovaleric acid (APV) reduces the firing frequency within action potential
      cluster. The rapid kinetics of self-excitation suggests a functional role of NMDA
      autoreceptors in prolonging periods of phasic firing in mitral cells.

PMID- 10899182
TI  - Sexually dimorphic regulation of NK-1 receptor-mediated electrophysiological
      responses in vagal primary afferent neurons.
AB  - Neurons can display sexual dimorphism in receptor expression, neurotransmitter
      release, and synaptic plasticity. We have detected sexual dimorphism in
      functional tachykinin receptors in vagal afferents (nodose ganglion neurons,
      NGNs) by studying the effects of hormonal variation on the depolarizing actions
      of substance P (SP) in female guinea pig NGNs. Using conventional "sharp"
      microelectrode recording plus measurement of serum 17beta-estradiol values, we
      examined SP responses in NGNs isolated from 1) ovariectomized females (OVX), 2)
      OVX females treated with 17beta-estradiol (OVX + E2), 3) pregnant females, and 4)
      males. Depending on various manipulations, 19-41% female NGNs were depolarized
      (16 +/- 1.1 mV, mean +/- SE) by 100 nM SP acting through NK-1 receptors. The NGNs
      of OVX + E2 females (41%, 15/37; 17 +/- 2.1 mV) and pregnant females (41%, 32/79;
      16 +/- 1.7 mV) were more likely to respond to SP than those of control males (P <
      0.001). The percentage of SP-sensitive NGNs from OVX females (19%, 21/109; 15 +/-
      1.9 mV) was not significantly different (P = 0.361) from that of control males
      (13%, 11/83; 13 +/- 2.0 mV). The serum 17beta-estradiol values for OVX + E2,
      pregnant, and OVX females were 23.9 +/- 3.3 pg/ml (n = 8), 16.0 +/- 2.4 pg/ml (n
      = 4), and 3.9 +/- 0.3 pg/ml (n = 8), respectively. These data indicate that there
      is a gender difference in NK-1 receptor expression in guinea pig nodose neurons,
      and they suggest that estrogen may modulate SP responsiveness in these neurons.

PMID- 10899183
TI  - Slowly adapting type I afferents from the sides and end of the finger respond to
      stimuli on the center of the fingerpad.
AB  - The central part of the fingerpad in anesthetized monkeys was stimulated by
      spheres varying in curvature indented into the skin. Responses were recorded from
      single slowly adapting type I primary afferent fibers (SAIs) innervating the
      sides and end of the distal segment of the stimulated finger. Although these
      afferents had receptive field centers that were remote from the stimulus, their
      responses were substantial. Increasing the curvature of the stimulus resulted in
      an increased response for most afferents. In general, responses increased most
      between stimuli with curvatures of 0 (flat) and 80.6 m(-1), with further
      increases in curvature having progressively smaller effects on the response. We
      calculated an index of sensitivity to changes in curvature; this index varied
      widely among the afferents but for most it was less than the index calculated for
      afferents innervating the fingerpad in the vicinity of the stimulus. Responses of
      all the SAIs increased when the contact force of the stimulus increased. An index
      of sensitivity to changes in contact force varied widely among the afferents but
      in all cases was greater than the index calculated for SAIs from the fingerpad
      itself. Neither the curvature sensitivity nor the force sensitivity of an
      afferent was related in any obvious way to the location of its receptive field
      center on the digit. There was only a minor correspondence between an afferent's
      sensitivity to force and its sensitivity to curvature. The large number of
      afferents innervating the border regions of the digit do respond to stimuli
      contacting the central fingerpad; they convey some information about the
      curvature of the stimulus and substantial information about contact force.

PMID- 10899184
TI  - Modulation of the startle response during human gait.
AB  - While many studies have shown that there is a phase-dependent modulation of
      proprioceptive and exteroceptive reflexes during gait, little is known about such
      modulation for auditory reflexes. To examine how startle reactions are
      incorporated in an ongoing gait pattern, unexpected auditory stimuli were
      presented to eight healthy subjects in six phases of the step cycle during
      walking on a treadmill at 4 km/h. For both legs, electromyographic activity (EMG)
      was recorded in the biceps femoris (BF), the rectus femoris (RF), the tibialis
      anterior (TA), and the soleus (SO). In addition, stance and swing phases of both
      legs, along with knee angles of both legs and the left ankle angle, were
      measured. All subjects showed various response peaks. Responses with latencies of
      approximately 60 ms (F1), approximately 85 ms (F2), and approximately 145 ms (F3)
      were found. The amplitude of the reflex responses was dependent on the timing of
      the startle stimulus in the step cycle. Although the startle response habituated
      rapidly, the phase-dependent modulation pattern generally remained the same. The
      phase-dependent amplitude modulations were not strictly correlated with the
      modulation of the background activity. The TA even showed a transition from
      facilitatory F2 responses during stance to suppressive responses during midswing.
      Responses were observed in both flexors and extensors, often in coactivation,
      especially during stance. Furthermore the gait characteristics showed a
      shortening of the subsequent step cycle and a small decrease in the range of
      motion of ankle and knees. These results suggest that the responses are adapted
      to achieve extra stability dependent on the phase of the step cycle. However,
      even in the first trials, the changes in kinematics were small allowing a smooth
      progression of gait.

PMID- 10899185
TI  - Dopamine D1/D5 receptor activation modulates a persistent sodium current in rat
      prefrontal cortical neurons in vitro.
AB  - The effects of dopamine (DA) on a persistent Na(+) current (I(NaP)) in layer V-VI
      prefrontal cortical (PFC) pyramidal cells were studied using whole cell voltage
      clamp recordings in rat PFC slices. After blocking K(+) and Ca (2+) currents, a
      tetrodotoxin-sensitive I(NaP) was activated by slow depolarizing voltage ramps or
      voltage steps. DA modulated the I(NaP) in a voltage-dependent manner: increased
      amplitude of I(NaP) at potentials more negative than -40 mV, but decreased at
      more positive potentials. DA also slowed the inactivation process of I(NaP). The
      D1/D5 dopamine receptor agonists SKF 38393, SKF 81297, and dihydrexidine (3-10
      microM), but not the dopamine D2/D3 receptor agonist qiunpirole (1-20 microM),
      mimicked the effects of DA on I(NaP). Modulation of I(NaP) by D1/D5 agonists was
      blocked by the D1/D5 antagonist SCH23390. Bath application of specific protein
      kinase C inhibitor, chelerhythrine, or inclusion of the specific protein kinase C
      inhibiting peptide([19-36]) in the recording pipette, but not protein kinase A
      inhibiting peptide([5-24]), blocked the effect of D1/D5 agonists on I(NaP). In
      current-clamp recordings, D1/D5 receptors activation enhanced the excitability of
      cortical pyramidal cells. Application of the D1/D5 agonist SKF 81297 induced a
      long-lasting decrease in the first spike latency in response to depolarizing
      current ramp. This was associated with a shift in the start of nonlinearity in
      the slope resistance to more negative membrane potentials. We proposed that this
      effect is due to a D1/D5 agonist-induced leftward shift in the activation of
      I(NaP). This enables DA to facilitate the firing of PFC neurons in response to
      depolarizing inputs.

PMID- 10899186
TI  - Temporal characteristics of error signals driving saccadic gain adaptation in the
      macaque monkey.
AB  - Saccadic gain (saccade amplitude/target amplitude) can be reduced gradually by
      repeatedly stepping the target backward during the saccade. The gain reduction
      produced by this paradigm is thought to be driven by an error signal created by
      the backstep. We investigated the effects of varying the timing of this error
      signal relative to the end of the saccade by using two different paradigms in
      macaques. In the brief backstep paradigm, the target was stepped backward 30%
      during the saccade but extinguished after different durations. For very short
      backstep durations (32 ms), little gain reduction occurred. As backstep duration
      increased, the amount of gain reduction also increased. When backstep duration
      reached 80 ms, the amount of gain reduction was just under that achieved during
      the conventional adaptation paradigm in which the backstep remained visible for
      1000-1200 ms. In the delayed backstep paradigm, as the saccade occurred, we
      extinguished the target and then, after a delay, illuminated it for 1 s at the
      backstep location. In most experiments with short delay times of 16-64 ms, the
      saccadic gain reduction reached that achieved during conventional adaptation. At
      delays of 112-208 ms, the amount of gain reduction decreased to approximately 75%
      of that reached during conventional adaptation. With still longer delays, the
      amount of gain reduction decreased more gradually. At delays of 750 ms, average
      gain reduction was 10%. By delays of 1.5 s, gain reduction had fallen essentially
      to zero. Taken together, these data suggest that the error signal must be present
      for a limited time ( approximately 80-100 ms) after the saccade to produce the
      most robust saccadic gain adaptation. However, errors present as long as 750 ms
      after the saccade still can produce a significant gain reduction.

PMID- 10899187
TI  - Saccades to sounds: effects of tracking illusory visual stimuli.
AB  - In 10 normal human subjects, we studied the accuracy of memory-guided saccades
      made to the remembered locations of visual targets and sounds. During the time of
      stimulus presentation, subjects were smoothly tracking a projected laser spot
      that was moving horizontally across a tangent screen, sinusoidally +/-15 degrees
      at 0.25 Hz. In one set of experiments, the laser spot moved across a 40 degrees x
      28 degrees random dot display that moved synchronously in the vertical plane;
      this induced a strong illusion that the trajectory of the laser spot was diagonal
      (variant of Duncker illusion). In control experiments, the laser spot moved
      across the same display, which was stationary. The visual targets and speakers
      were at six locations (range +/-15 degrees ) in the horizontal plane. Saccades
      made to the remembered locations of targets presented during background motion
      (illusion) were significantly (P < 0.05) more inaccurate than with the background
      stationary (control) in 9 of 10 subjects for lights and in 6 of 10 subjects for
      sounds. As a group, the median change in errors due to the Duncker illusion was
      approximately 2.5 times greater for visual compared with acoustic targets (P <
      0.001). These findings are consistent with electrophysiological studies which
      have shown that neurons in the primate lateral intraparietal area (LIP) may
      respond to both visual and auditory targets and these neurons are also influenced
      by the Duncker illusion during programming of memory-guided saccades.

PMID- 10899188
TI  - Electrophysiological features of morphological Dogiel type II neurons in the
      myenteric plexus of pig small intestine.
AB  - By intracellular recording, 99 myenteric neurons with Dogiel type II morphology
      were electrophysiologically characterized in the porcine ileum and further
      subdivided into three groups based on their different types of
      afterhyperpolarization (AHP). In response to a depolarizing current injection, a
      fast AHP (fAHP; duration 34 +/- 11 ms; amplitude -11 +/- 6 mV; mean +/- SD)
      immediately followed every action potential in all neurons. In 32% of the
      neurons, this fAHP was the sole type of hyperpolarization recorded. Statistical
      analysis revealed the presence of two neuronal subpopulations that displayed
      either a long-lasting medium AHP (mAHP; duration after a single spike 773 +/- 753
      ms; 51% of neurons) or a slow AHP (sAHP; 4, 205 +/- 1,483 ms; 17%). Slow AHP
      neurons also differed from mAHP neurons in the delayed onset of the AHP (mAHP 0
      ms; sAHP 100-200 ms), as well as in maximum amplitude values and in the time to
      reach this amplitude (t(max); 148 +/- 11 ms vs. 628 +/- 108 ms). Medium AHP
      neurons further differed from the sAHP neurons in the occurrence of the AHP
      following subthreshold current injection and in their resting membrane potential
      (mAHP, -53 +/- 8 mV; sAHP, -62 +/- 10 mV). Medium AHP and sAHP behaved similarly
      in that a higher number of spikes increased their amplitude and duration, but not
      t(max). The majority of neurons fired multiple spikes (up to 25) in response to a
      500-ms current injection (81/99) and showed a clear TTX-resistant shoulder on the
      repolarizing phase of the action potential (77/99), irrespective of the presence
      of sAHP or mAHP. These results demonstrate that the porcine Dogiel type II
      neurons differ in various essential electrophysiological properties from their
      morphological counterparts in the guinea pig ileal myenteric plexus. The most
      striking interspecies differences were the low occurrence of sAHP (17% vs. 80-90%
      in guinea pig) with relatively small amplitude (-5 vs. -20 mV), the high
      occurrence of mAHPs (unusual in guinea pig) and the ability to fire long spike
      trains (up to 25 spikes vs. 1-3 in guinea pig). In fact, Dogiel type II neurons
      in porcine ileum combine distinct electrophysiological features considered
      typical of either S-type or sAHP-type neurons in guinea pig. It can therefore be
      concluded that in spite of a similar morphology, Dogiel type II neurons do not
      behave electrophysiologically in a universal way in large and small mammals.

PMID- 10899190
TI  - Disparity selectivity of neurons in monkey inferior temporal cortex.
AB  - The inferior temporal cortex (IT) of the monkey, a final stage in the ventral
      visual pathway, has been known to process information on two-dimensional (2-D)
      shape, color, and texture. On the other hand, the dorsal visual pathway leading
      to the posterior parietal cortex has been known to process information on
      location in space. Likewise, neurons selective for binocular disparity, which
      convey information on depth, have been found mainly in areas along the dorsal
      visual pathway. Here, we report that many neurons in the IT are also selective
      for binocular disparity. We recorded extracellular activity from IT neurons and
      found that more than half of the neurons changed their response depending on the
      disparity added. The change was not attributed to monocular responses or eye
      movements. Most neurons selective for disparity were "near" or "far" cells; they
      preferred either crossed or uncrossed disparity, and only a small population was
      tuned to zero disparity. Disparity-selective neurons were also selective for
      shape. Most preferred the same type of disparity irrespective of the shape
      presented. Disparity preference was also invariant for the fronto-parallel
      translation of the stimuli in most of the neurons. Finally, nearby neurons
      exhibited similar disparity selectivity, suggesting the existence of a functional
      module for processing of binocular disparity in the IT. From the above and our
      recent findings, we suggest that the IT integrates shape and binocular disparity
      information, and plays an important role in the reconstruction of three
      dimensional (3-D) surfaces.

PMID- 10899189
TI  - Dopamine depresses excitatory synaptic transmission onto rat subicular neurons
      via presynaptic D1-like dopamine receptors.
AB  - Schizophrenia is considered to be associated with an abnormal functioning of the
      hippocampal output. The high clinical potency of antipsychotics that act as
      antagonists at dopamine (DA) receptors indicate a hyperfunction of the
      dopaminergic system. The subiculum obtains information from area CA1 and the
      entorhinal cortex and represents the major output region of the hippocampal
      complex. To clarify whether an enhanced dopaminergic activity alters the
      hippocampal output, the effect of DA on alveus- and perforant path-evoked
      excitatory postsynaptic currents (EPSCs) in subicular neurons was examined using
      conventional intracellular and whole cell voltage-clamp recordings. Dopamine (100
      microM) depressed alveus-elicited (S)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor-mediated EPSCs to 56 +/- 8% of control
      while perforant path-evoked EPSCs were attenuated to only 76 +/- 7% of control.
      Dopamine had no effect on the EPSC kinetics. Dopamine reduced the frequency of
      spontaneous miniature EPSCs without affecting their amplitudes. The sensitivity
      of subicular neurons to the glutamate receptor agonist (S)-alpha-amino-3-hydoxy-5
      methyl-4-isoxazolepropionic acid was unchanged by DA pretreatment, excluding a
      postsynaptic mechanism for the observed reduction of excitatory synaptic
      transmission. The effect of DA on evoked EPSCs was mimicked by the D1 receptor
      agonist SFK 38393 and partially antagonized by the D1 receptor antagonist SCH
      23390. While the D2 receptor agonist quinelorane failed to reduce the EPSCs, the
      D2 receptor antagonist sulpiride did not block the action of DA. The results
      indicate that DA strongly depresses the hippocampal and the entorhinal excitatory
      input onto subicular neurons by decreasing the glutamate release following
      activation of presynaptic D1-like DA receptors.

PMID- 10899191
TI  - Depolarization-induced calcium channel facilitation in rod photoreceptors is
      independent of G proteins and phosphorylation.
AB  - Depolarization-induced facilitation of L-type Ca channels in rod photoreceptors
      was investigated with nystatin-perforated and ruptured whole cell patch-clamp
      techniques in cells isolated from tiger salamander retina. Induction of
      facilitation was voltage dependent with a half-maximal effect seen at prepulse
      potentials near +31 mV. Reversal of facilitation was time dependent with fast
      (tau approximately 20 ms) and slow (tau approximately 1 s) components at -60 mV.
      Incubation of cells with pertussis toxin or intracellular administration of
      guanosine 5'-O-(3-thiotriphosphate) or guanosine 5'-O-(2-thiodiphosphate) had no
      effect on the degree to which facilitation could be evoked, implying the absence
      of a significant role for G proteins. Application of the phosphatase inhibitor
      okadaic acid or inclusion of ATP, to boost levels of phosphorylation, or
      inclusion of 5'adenylylimidophosphate or inhibitors of protein kinase in the
      pipette, to reduce levels of phosphorylation, had no effect on the development of
      facilitation, suggesting that phosphorylation has little or no role in this
      phenomenon. These results show that the L-type Ca channels in rod photoreceptors,
      which appear to be composed of alpha(1F)-like subunits, undergo voltage-dependent
      facilitation in a manner that differs from some other L-type Ca channels which
      undergo facilitation via phosphorylation or through G-protein-mediated
      inhibition.

PMID- 10899192
TI  - Major potassium conductance in type I hair cells from rat semicircular canals:
      characterization and modulation by nitric oxide.
AB  - Mammalian vestibular organs have two types of hair cell, type I and type II,
      which differ morphologically and electrophysiologically. Type I hair cells alone
      express an outwardly rectifying current, I(K, L), which activates at relatively
      negative voltages. We used whole cell and patch configurations to study I(K,L) in
      hair cells isolated from the sensory epithelia of rat semicircular canals. I(K,L)
      was potassium selective, blocked by 4-aminopyridine, and permeable to internal
      cesium. It activated with sigmoidal kinetics and was half-maximally activated at 
      74.5 +/- 1.6 mV (n = 35; range -91 to -50 mV). It was a very large conductance
      (91 +/- 8 nS at -37 mV; 35 nS/pF for a cell of average size). Patch recordings
      from type I cells revealed a candidate ion channel with a conductance of 20-30
      pS. Because I(K,L) was activated at the resting potential, the cells had low
      input resistances (R(m)): median 25 MOmega at -67 mV versus 1.3 GOmega for type
      II cells. Consequently, injected currents comparable to large transduction
      currents (300 pA) evoked small (</=10 mV) voltage responses. The cells' small
      voltage responses and negative resting potentials (V(R) = -81.3 +/- 0.2 mV, n =
      144) pose a problem for afferent neurotransmission: how does the receptor
      potential depolarize the cell into the activation range of Ca(2+) channels
      (positive to -60 mV) that mediate transmitter release? One possibility, suggested
      by spontaneous positive shifts in the activation range of I(K,L) during whole
      cell recording, is that the activation range might be modulated in vivo. Any
      factor that reduces the number of I(K,L) channels open at V(R) will increase R(m)
      and depolarize V(R). Nitric oxide (NO) is an ion channel modulator that is
      present in vestibular epithelia. Four different NO donors, applied externally,
      inhibited the I(K,L) conductance at -67 mV, with mean effects ranging from 33 to
      76%. The NO donor sodium nitroprusside inhibited channel activity in patches when
      they were cell-attached but not excised, suggesting an intracellular cascade.
      Consistent with an NO-cGMP cascade, 8-bromo-cGMP also inhibited whole cell
      I(K,L). Ca(2+)-dependent NO synthase is reported to be in hair cells and nerve
      terminals in the vestibular epithelium. Excitatory input to vestibular organs may
      lead, through Ca(2+) influx, to NO production and inhibition of I(K,L). The
      resulting increase in R(m) would augment the receptor potential, a form of
      positive feedback.

PMID- 10899193
TI  - Covariation of primate dorsal premotor cell activity with direction and amplitude
      during a memorized-delay reaching task.
AB  - Extensive behavioral evidence suggests that the direction and amplitude of
      reaching movements are planned as two independent parameters by the motor system.
      However, whereas direction-related activity has been well documented by
      neurophysiological studies in many motor structures including the dorsal premotor
      cortex (PMd), there is much less concensus about the prominence and timing of
      amplitude-related premotor activity. We studied this issue using an instructed
      delay task in which prior information about target location (direction and
      distance) must be memorized before movement initiation. The results show that
      prior information about distance is reflected in PMd activity during the delay
      period well before movement initiation, and begins to be expressed as early as
      150 ms after presentation of target location. The prominence of neural correlates
      with direction is relatively constant throughout the trial, but distance
      correlates become gradually more prominent with time, both during and after the
      delay period. A small majority of cells were modulated only by direction during
      the delay period, but very few were modulated only by distance, and most of the
      rest were modulated by both. Therefore PMd neurons usually process information
      about distance only in conjunction with directional information. These results do
      not support a separate neuronal substrate for distance in PMd, but do not
      preclude its existence elsewhere. The results also support a progressive change
      in the nature of the movement-related representation in PMd with time in an
      instructed-delay paradigm.

PMID- 10899194
TI  - Responses of inferior colliculus neurons to amplitude-modulated intracochlear
      electrical pulses in deaf cats.
AB  - Current cochlear prostheses use amplitude-modulated pulse trains to encode
      acoustic signals. In this study we examined the responses of inferior colliculus
      (IC) neurons to sinusoidal amplitude-modulated pulses and compared the maximum
      unmodulated pulse rate (Fmax) to which they responded with the maximum modulation
      frequency (maxFm) that they followed. Consistent with previous results, responses
      to unmodulated pulses were all low-pass functions of pulse rate. Mean Fmax to
      unmodulated pulses was 104 pulses per second (pps) and modal Fmax was 60 pps.
      Above Fmax IC neurons ceased responding except for an onset burst at the
      beginning of the stimulus. However, IC neurons responded to much higher pulse
      rates when these pulses were amplitude modulated; 74% were relatively insensitive
      to carrier rate and responded to all modulated carriers including those exceeding
      600 pps. In contrast, the responses of these neurons (70%) were low-pass
      functions of modulation frequency, and the remaining (30%) had band-pass
      functions with a maxFm of 42 and 34 Hz, respectively. Thus temporal resolution of
      IC neurons for modulated frequencies is significantly lower than that for
      unmodulated pulses. These two measures of temporal resolution (Fmax and maxFm)
      were uncorrelated (r(2) = 0.101). Several parameters influenced the amplitude and
      temporal structure of modulation responses including modulation depth, overall
      intensity and modulation-to-carrier rate ratio. We observed distortions in unit
      responses to amplitude-modulated signals when this ratio was 1/4 to 1/6. Since
      most current cochlear implant speech processors permit ratios that are
      significantly greater than this, severe distortion and signal degradation may
      occur frequently in these devices.

PMID- 10899195
TI  - Long-latency component of the stretch reflex in human muscle is not mediated by
      intramuscular stretch receptors.
AB  - Reflex responses to mechanical stimulation of muscle (brief imposed movement)
      were investigated. Reflexes were elicited in the forefinger, recording from the
      first dorsal interosseous (FDI), and in the foot, recording from soleus. These
      responses typically consisted of a short-latency component (M1) and a long
      latency component (M2) at 33 ms and 53 ms, respectively, after the stimulus in
      the case of FDI, and 37 ms and 68 ms, respectively, in soleus upon stimulation of
      the sole of the foot. Normally, when a muscle is stretched by a mechanical
      stimulus (either naturally or by an experimentally imposed movement), both skin
      receptors and muscle stretch receptors are activated. It is possible, however, to
      devise stimulation parameters where this is not the case. Fixating the finger
      with plasticine enables the effects of skin stimulation to be studied without
      stretching the FDI muscle. On the other hand, tapping a long tendon allows muscle
      stretch receptors to be activated without involving skin or subcutaneous
      structures. Component M1 was always abolished by finger fixation in 40 trials on
      10 subjects, with M2 being essentially unchanged in latency, duration, or
      amplitude. Reflex responses were obtained in soleus muscle in nine experiments by
      prodding the sole of the foot (thereby stimulating both skin and muscle stretch
      receptors). Alternatively, the tendo achilles was prodded (which solely activates
      stretch receptors in the muscle). In the former, M1 and M2 were generated. In the
      latter, only M1 was produced. It is concluded that the long-latency component of
      the stretch reflex, M2, originates in skin and/or subcutaneous nerve terminals
      and that no part of M2 originates in muscle stretch receptors.

PMID- 10899196
TI  - Robustness and variability of neuronal coding by amplitude-sensitive afferents in
      the weakly electric fish eigenmannia.
AB  - We investigated the variability of P-receptor afferent spike trains in the weakly
      electric fish, Eigenmannia, to repeated presentations of random electric field
      AMs (RAMs) and quantified its impact on the encoding of time-varying stimuli. A
      new measure of spike timing jitter was developed using the notion of spike train
      distances recently introduced by Victor and Purpura. This measure of variability
      is widely applicable to neuronal responses, irrespective of the type of stimuli
      used (deterministic vs. random) or the reliability of the recorded spike trains.
      In our data, the mean spike count and its variance measured in short time windows
      were poorly correlated with the reliability of P-receptor afferent spike trains,
      implying that such measures provide unreliable indices of trial-to-trial
      variability. P-receptor afferent spike trains were considerably less variable
      than those of Poisson model neurons. The average timing jitter of spikes lay
      within 1-2 cycles of the electric organ discharge (EOD). At low, but not at high
      firing rates, the timing jitter was dependent on the cutoff frequency of the
      stimulus and, to a lesser extent, on its contrast. When spikes were artificially
      manipulated to increase jitter, information conveyed by P-receptor afferents was
      degraded only for average jitters considerably larger than those observed
      experimentally. This suggests that the intrinsic variability of single spike
      trains lies outside of the range where it might degrade the information conveyed,
      yet still allows for improvement in coding by averaging across multiple afferent
      fibers. Our results were summarized in a phenomenological model of P-receptor
      afferents, incorporating both their linear transfer properties and the
      variability of their spike trains. This model complements an earlier one proposed
      by Nelson et al. for P-receptor afferents of Apteronotus. Because of their
      relatively high precision with respect to the EOD cycle frequency, P-receptor
      afferent spike trains possess the temporal resolution necessary to support
      coincidence detection operations at the next stage in the amplitude-coding
      pathway.

PMID- 10899197
TI  - Spinal nerve injury enhances subthreshold membrane potential oscillations in DRG
      neurons: relation to neuropathic pain.
AB  - Primary sensory neurons with myelinated axons were examined in vitro in excised
      whole lumbar dorsal root ganglia (DRGs) taken from adult rats up to 9 days after
      tight ligation and transection of the L(5) spinal nerve (Chung model of
      neuropathic pain). Properties of subthreshold membrane potential oscillations,
      and of repetitive spike discharge, were examined. About 5% of the DRG neurons
      sampled in control DRGs exhibited high-frequency, subthreshold sinusoidal
      oscillations in their membrane potential at rest (V(r)), and an additional 4.4%
      developed such oscillations on depolarization. Virtually all had noninflected
      action potentials (A(0) neurons). Amplitude and frequency of subthreshold
      oscillations were voltage sensitive. A(0) neurons with oscillations at V(r)
      appear to constitute a population distinct from A(0) neurons that oscillate only
      on depolarization. Axotomy triggered a significant increase in the proportion of
      neurons exhibiting subthreshold oscillations both at V(r) and on depolarization.
      This change occurred within a narrow time window 16-24 h postoperative. Axotomy
      also shifted the membrane potential at which oscillation amplitude was maximal to
      more negative (hyperpolarized) values, and lowered oscillation frequency at any
      given membrane potential. Most neurons that had oscillations at V(r), or that
      developed them on depolarization, began to fire repetitively when further
      depolarized. Spikes were triggered by the depolarizing phase of oscillatory
      sinusoids. Neurons that did not develop subthreshold oscillations never
      discharged repetitively and rarely fired more than a single spike or a short
      burst, on step depolarization. The most prominent spike waveform parameters
      distinguishing neurons capable of generating subthreshold oscillations, and hence
      repetitive firing, was their brief postspike afterhyperpolarization (AHP) and
      their low single-spike threshold. Neurons that oscillated at V(r) tended to have
      a more prolonged spike, with slower rise- and fall-time kinetics, and lower spike
      threshold, than cells that oscillated only on depolarization. The main effects of
      axotomy were to increase spike duration, slow rise- and fall-time kinetics, and
      reduce single-spike threshold. Tactile allodynia following spinal nerve injury is
      thought to result from central amplification ("central sensitization") of
      afferent signals entering the spinal cord from residual intact afferents. The
      central sensitization, in turn, is thought to be triggered and maintained in the
      Chung model by ectopic firing originating in the axotomized afferent neurons.
      Axotomy by spinal nerve injury enhances subthreshold membrane potential
      oscillations in DRG neurons, augments ectopic discharge, and hence precipitates
      neuropathic pain.

PMID- 10899199
TI  - Temporal discharge patterns evoked by rapid sequences of wide- and narrowband
      clicks in the primary auditory cortex of cat.
AB  - The present study investigated neural responses to rapid, repetitive stimuli in
      the primary auditory cortex (A1) of cats. We focused on two important issues
      regarding cortical coding of sequences of stimuli: temporal discharge patterns of
      A1 neurons as a function of inter-stimulus interval and cortical mechanisms for
      representing successive stimulus events separated by very short intervals. These
      issues were studied using wide- and narrowband click trains with inter-click
      intervals (ICIs) ranging from 3 to 100 ms as a class of representative sequential
      stimuli. The main findings of this study are 1) A1 units displayed, in response
      to click train stimuli, three distinct temporal discharge patterns that we
      classify as regions I, II, and III. At long ICIs nearly all A1 units exhibited
      typical stimulus-synchronized response patterns (region I) consistent with
      previously reported observations. At intermediate ICIs, no clear temporal
      structures were visible in the responses of most A1 units (region II). At short
      ICIs, temporal discharge patterns are characterized by the presence of either
      intrinsic oscillations (at approximately 10 Hz) or a change in discharge rate
      that was a monotonically decreasing function of ICI (region III). In some A1
      units, temporal discharge patterns corresponding to region III were absent. 2)
      The boundary between regions I and II (synchronization boundary) had a median
      value of 39.8 ms ICI ([25%, 75%] = [20.4, 58. 8] ms ICI; n = 131). The median
      boundary between regions II and III was estimated at 6.3 ms ([25%, 75%] = [5.2,
      9.7] ms ICI; n = 47) for units showing rate changes (rate-change boundary). 3)
      The boundary values between different regions appeared to be relatively
      independent of stimulus intensity (at modest sound levels) or the bandwidth of
      the clicks used. 4) There is a weak correlation between a unit's synchronization
      boundary and its response latency. Units with shorter latencies appeared to also
      have smaller boundary values. And 5) based on these findings, we proposed a two
      stage model for A1 neurons to represent a wide range of ICIs. In this model, A1
      uses a temporal code for explicitly representing long ICIs and a rate code for
      implicitly representing short ICIs.

PMID- 10899198
TI  - Apparent motion produces multiple deficits in visually guided smooth pursuit eye
      movements of monkeys.
AB  - We used apparent motion targets to explore how degraded visual motion alters
      smooth pursuit eye movements. Apparent motion targets consisted of brief
      stationary flashes with a spatial separation (Deltax), temporal separation
      (Deltat), and apparent target velocity equal to Deltax/Deltat. Changes in pursuit
      initiation were readily observed when holding target velocity constant and
      increasing the flash separation. As flash separation increased, the first deficit
      observed was an increase in the latency to peak eye acceleration. Also seen was a
      paradoxical increase in initial eye acceleration. Further increases in the flash
      separation produced larger increases in latency and resulted in decreased eye
      acceleration. By varying target velocity, we were able to discern that the visual
      inputs driving pursuit initiation show both temporal and spatial limits. For
      target velocities above 4-8 degrees /s, deficits in the initiation of pursuit
      were seen when Deltax exceeded 0.2-0.5 degrees, even when Deltat was small. For
      target velocities below 4-8 degrees /s, deficits appeared when Deltat exceeded 32
      64 ms, even when Deltax was small. Further experiments were designed to determine
      whether the spatial limit varied as retinal and extra-retinal factors changed.
      Varying the initial retinal position of the target for motion at 18 degrees /s
      revealed that the spatial limit increased as a function of retinal eccentricity.
      We then employed targets that increased velocity twice, once from fixation and
      again during pursuit. These experiments revealed that, as expected, the spatial
      limit is expressed in terms of the flash separation on the retina. The spatial
      limit is uninfluenced by either eye velocity or the absolute velocity of the
      target. These experiments also demonstrate that "initiation" deficits can be
      observed during ongoing pursuit, and are thus not deficits in initiation per se.
      We conclude that such deficits result from degradation of the retino-centric
      motion signals that drive pursuit eye acceleration. For large flash separations,
      we also observed deficits in the maintenance of pursuit: sustained eye velocity
      failed to match the constant apparent target velocity. Deficits in the
      maintenance of pursuit depended on both target velocity and Deltat and did not
      result simply from a failure of degraded image motion signals to drive eye
      acceleration. We argue that such deficits result from a low gain in the eye
      velocity memory that normally supports the maintenance of pursuit. This low gain
      may appear because visual inputs are so degraded that the transition from
      fixation to tracking is incomplete.

PMID- 10899200
TI  - Chronic exposure to ethanol alters GABA(A) receptor-mediated responses of layer
      II pyramidal cells in adult rat piriform cortex.
AB  - This study examined the effect of chronic exposure to ethanol on gamma
      aminobutyric acid type-A (GABA(A)) receptor-mediated responses of layer II
      pyramidal neurons of the piriform cortex. Slices containing the piriform cortex
      were derived from pair-fed adult rats maintained on ethanol-supplemented or
      control liquid diet for 30 days. Responses of identified layer II pyramidal
      neurons to exogenously applied GABA were monitored by whole-cell patch-clamp
      recording. Chronic exposure to ethanol resulted in a rightward shift in the
      EC(50) of GABA and a decrease in the amplitude of maximal GABA response. GABA
      induced responses were modulated by acutely applied ethanol (10-100 mM) in both
      chronic ethanol-treated and control groups. No significant difference was found
      in the average change in GABA response, suggesting that tolerance to acute
      ethanol exposure did not develop. When the modulatory responses of individual
      cells were classified and grouped as either being attenuating, potentiating, or
      having no effect, the incidence of potentiation in the ethanol-treated group was
      significantly higher. Consistent with the absence of tolerance to acute ethanol,
      cross-tolerance to diazepam was not observed following 30 days of treatment with
      ethanol. These results are discussed in light of regionally specific effects of
      chronic ethanol treatment on GABA(A) receptor-mediated responses of layer II
      piriform cortical neurons.

PMID- 10899201
TI  - Auditory temporal processing: responses to sinusoidally amplitude-modulated tones
      in the inferior colliculus.
AB  - Time-varying envelopes are a common feature of acoustic communication signals
      like human speech and induce a variety of percepts in human listeners. We studied
      the responses of 109 single neurons in the inferior colliculus (IC) of the
      anesthetized Mongolian gerbil to contralaterally presented sinusoidally amplitude
      modulated (SAM) tones with a wide range of parameters. Modulation transfer
      functions (MTFs) based on average spike rate (rMTFs) showed regions of
      enhancement and suppression, where spike rates increased or decreased
      respectively as stimulus modulation depth increased. Specifically, almost all IC
      rMTFs could be described by some combination of a primary and a secondary region
      of enhancement and an intervening region of suppression, with these regions
      present to varying degrees in individual rMTFs. rMTF characteristics of most
      neurons were dependent on sound pressure level (SPL). rMTFs in most neurons with
      "onset" or "onset-sustained" peri-stimulus time histograms (PSTHs) in response to
      brief pure tones showed only a peaked primary region of enhancement. The region
      of suppression tended to occur in neurons with "sustained" or "pauser" PSTHs, and
      usually emerged at higher SPLs. The secondary region of enhancement was only
      found in eight neurons. The lowest modulation frequency at which the spike rate
      reached a clear peak ("best modulation frequency" or BMF) was measured. All but
      two mean BMFs lay between 0 and 100 Hz. Fifty percent of the 49 neurons tested
      over at least a 20-dB range of SPLs showed a BMF variation larger than 66% of
      their mean BMF. MTFs based on vector strength (tMTFs) showed a variety of
      patterns; although mostly similar to those reported from the cochlear nucleus,
      tMTFs of IC neurons showed higher maximum values, smaller dynamic range with
      depth, and a lower high-frequency limit for significant phase locking. Systematic
      and large increases in phase-lead commonly occurred as SPL increased. rMTFs
      measured at multiple carrier frequencies (F(c)s) showed that the suppressive
      region was not the result of sideband inhibition. There was no systematic
      relationship between BMF and F(c) of stimulation in the cells studied, even at
      low carrier frequencies. The results suggest various possible mechanisms that
      could create IC MTFs, and strongly support the idea that inhibitory inputs shape
      the rMTF by sharpening regions of enhancement and creating a suppressive region.
      The paucity of BMFs above 100 Hz argues against simple rate-coding schemes for
      pitch. Finally, any labeled line or topographic representation of modulation
      frequency is unlikely to be independent of SPL.

PMID- 10899202
TI  - Effects of applied electric fields on low-calcium epileptiform activity in the
      CA1 region of rat hippocampal slices.
AB  - It is well established that exogenous electric fields can suppress activity
      obtained in different models of epileptiform discharge such as penicillin and
      high potassium. In the low-calcium model of epilepsy, spontaneous epileptiform
      bursting is generated in the absence of synaptic transmission. It has been
      suggested that ephaptic interactions play a critical role in neuronal
      synchronization and burst propagation in this nonsynaptic model. We, therefore,
      tested the hypothesis that low-calcium bursting induced in the CA1 region of
      transverse and longitudinal hippocampal slices should be highly sensitive to
      exogenous electric fields. Uniform, low amplitude DC electric fields were applied
      during spontaneous low-calcium epileptiform activity. Modulation and full
      suppression of epileptiform activity was observed at field strengths between 1
      and 5 mV/mm, a value significantly lower than in other in vitro models of
      epilepsy. We further investigated the hypothesis that the efficacy of electrical
      fields was related to changes in the extracellular space. Our results suggest
      that the osmolality of the perfusate can modulate the efficacy of electric
      fields. It was also observed that the ability of a field to suppress or modulate
      low-calcium activity was highly dependent on its orientation, polarity, as well
      as magnitude. Finally, it was observed that the extracellular potassium "waves"
      that normally accompany individual epileptiform events was abolished when the
      individual events were suppressed. These results suggest that DC fields modulate
      and suppress low-calcium activity by directly polarizing CA1 pyramidal cells.

PMID- 10899203
TI  - Reversibility and cation selectivity of the K(+)-Cl(-) cotransport in rat central
      neurons.
AB  - The reversibility and cation selectivity of the K(+)-Cl(-) cotransporter (KCC),
      which normally extrudes Cl(-) out of neurons, was investigated in dissociated
      lateral superior olive neurons of rats using the gramicidin perforated patch
      technique. Intracellular Cl(-) activity (alpha[Cl(-)](i)) was maintained well
      below electrochemical equilibrium as determined from the extracellular Cl(-)
      activity and the holding potential, where the pipette and external solutions
      contained 150 mM K(+) ([K(+)](pipette)) and 5 mM K(+) ([K(+)](o)), respectively.
      Extracellular application of 1 mM furosemide or elevated [K(+)](o) increased
      alpha[Cl(-)](i). When the pipette solution contained 150 mM Cs(+)
      ([Cs(+)](pipette)), alpha[Cl(-)](i) increased to a value higher than the passive
      alpha[Cl(-)](i). An increase of alpha[Cl(-)](i) with the [Cs(+)](pipette) was not
      due to the simple blockade of net KCC by the intracellular Cs(+) since alpha[Cl(
      )](i), with the pipette solution containing 75 mM Cs(+) and 75 mM K(+), reached a
      value between those obtained using the [K(+)](pipette) and the [Cs(+)](pipette).
      The higher-than-passive alpha[Cl(-)](i) with the [Cs(+)](pipette) was reduced by
      1 mM furosemide, but not by 20 microM bumetanide or Na(+)-free external solution,
      indicating that the accumulation of [Cl(-)](i) in the [Cs(+)](pipette) was
      mediated by a KCC operating in a reversed mode rather than by Na(+)-dependent,
      bumetanide-sensitive mechanisms. Replacement of K(+) in the pipette solution with
      either Li(+) or Na(+) mimicked the effect of Cs(+) on alpha[Cl(-)](i). On the
      other hand, Rb(+) mimicked K(+) in the pipette solution. These results indicate
      that K(+) and Rb(+), but not Cs(+), Li(+), or Na(+), can act as substrates of KCC
      in LSO neurons.

PMID- 10899204
TI  - Excitatory cortical inputs to pallidal neurons via the subthalamic nucleus in the
      monkey.
AB  - How the motor-related cortical areas modulate the activity of the output nuclei
      of the basal ganglia is an important issue for understanding the mechanisms of
      motor control by the basal ganglia. In the present study, by using awake monkeys,
      the polysynaptic effects of electrical stimulation in the forelimb regions of the
      primary motor and primary somatosensory cortices on the activity of globus
      pallidus (GP) neurons, especially mediated by the subthalamic nucleus (STN), have
      been characterized. Cortical stimulation induced an early, short-latency
      excitation followed by an inhibition and a late excitation in neurons of both the
      external and internal segments of the GP. It also induced an early, short-latency
      excitation followed by a late excitation and an inhibition in STN neurons. The
      early excitation in STN neurons preceded that in GP neurons. Blockade of STN
      neuronal activity by muscimol (GABA(A) receptor agonist) injection resulted in
      abolishment of both the early and late excitations evoked in GP neurons by
      cortical stimulation. At the same time, the spontaneous discharge rate of GP
      neurons decreased, pauses between the groups of spikes of GP neurons became
      prominent, and the firing pattern became regular. Injection of (+/-)-3-(2
      carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) [N-methyl-D-aspartate
      (NMDA) receptor antagonist], but not 1,2,3, 4-tetrahydro-6-nitro-2,3-dioxo
      benzo[f]quinoxaline-7-sulfonamide disodium [NBQX (non-NMDA receptor antagonist)],
      into the STN attenuated the early and late excitations in GP neurons, suggesting
      that cortico-subthalamic transmission is mediated mainly by NMDA receptors.
      Interference with the pallido-subthalamic transmission by bicuculline (GABA(A)
      receptor antagonist) injection into the STN made the inhibition distinct without
      affecting the early excitation. The present results indicate that the cortico
      subthalamo-pallidal pathway conveys powerful excitatory effects from the motor
      related cortical areas to the GP with shorter conduction time than the effects
      conveyed through the striatum.

PMID- 10899205
TI  - Response of neurons in the lateral intraparietal area to a distractor flashed
      during the delay period of a memory-guided saccade.
AB  - Recent experiments raised the possibility that the lateral intraparietal area
      (LIP) might be specialized for saccade planning. If this was true, one would
      expect a decreased sensitivity to irrelevant visual stimuli appearing late in the
      delay period of a memory-guided delayed-saccade task to a target outside the
      neurons' receptive fields. We trained two monkeys to perform a standard memory
      guided delayed-saccade task and a distractor task in which a stimulus flashed for
      200 ms at a predictable time 300-100 ms before the end of the delay period. We
      used two locations, one in the most active part of the receptive field and
      another well outside the receptive field. We used six kinds of trials randomly
      intermixed: simple delayed-saccade trials into or away from the receptive field
      and distractor trials with saccade target and distractor both in the receptive
      field, both out of the receptive field, or one at each location. This enabled us
      to study the response to the distractor as a function of the monkey's preparation
      of a memory-guided delayed-saccade task. We had assumed that the preparation of a
      saccade away from the receptive field would result in an attenuation of the
      response to the distractor, i.e., a distractor at the location of the saccade
      goal would evoke a greater response than when it appeared at a location far from
      the saccade goal. Instead we found that neurons exhibited either a normal or an
      enhanced visual response to the distractor during the memory period when the
      target flashed outside the receptive field. When the distractor flashed at the
      location of the saccade target, the response to the distractor was either
      unchanged or diminished. The response to a distractor away from the target
      location of a memory-guided saccade was even greater than the response to the
      same target when it was the target for the memory-guided saccade task. Immediate
      presaccadic activity did not distinguish between a saccade to the receptive field
      when there was no distractor and a distractor in the receptive field when the
      monkey made a saccade elsewhere. Nonetheless the distractor had no significant
      effect on the saccade latency, accuracy, or velocity despite the brisk response
      it evoked immediately before the saccade. We suggest that these results are
      inconsistent with a role for LIP in the specific generation of saccades, but they
      are consistent with a role for LIP in the generation of visual attention.

PMID- 10899206
TI  - Mitochondrial and intrinsic optical signals imaged during hypoxia and spreading
      depression in rat hippocampal slices.
AB  - During hypoxia in the CA1 region of the rat hippocampus, spreading-depression
      like depolarization (hypoxic spreading depression or HSD) is accompanied by both
      a negative shift of the extracellular DC potential (DeltaV(o)), and a sharp
      decrease in light transmittance (intrinsic optical signal or IOS). To investigate
      alterations in mitochondrial function during HSD and normoxic spreading
      depression (SD), we simultaneously imaged mitochondrial depolarization, using
      rhodamine-123 (R123) fluorescence, and IOS while monitoring extracellular
      voltage. Three major phases of the R123 signal were observed during hypoxia: a
      gradual, diffuse fluorescence increase, a sharp increase in fluorescence
      coincident with the HSD-related DeltaV(o), primarily in the CA1 region, and a
      plateau-like phase if reoxygenation is delayed after HSD onset, persisting until
      reoxygenation occurs. Two phases occurred following re-oxygenation: an abrupt and
      then slow decrease in fluorescence to near baseline and a slow secondary increase
      to slightly above baseline and a late recovery. Parallel phases of the IOS
      response during hypoxia were also observed though delayed compared with the R123
      responses: an initial increase, a large decrease coincident with the HSD-related
      DeltaV(o), and a trough following HSD. After reoxygenation, there occurred a
      delayed increase in transmittance and then a slow decrease, returning to near
      baseline. When Ca(2+) was removed from the external medium, resulting in complete
      synaptic blockade, the mitochondrial response to hypoxia did not significantly
      differ from control (normal Ca(2+)) conditions. In slices maintained in low
      chloride (2.4 mM) medium, a dramatic reversal in the direction of the IOS signal
      associated with HSD occurred, and the R123 signal during HSD was severely
      attenuated. Normoxic SD induced by micro-injection of KCl was also associated
      with a decrease in light transmittance and a sharp increase in R123 fluorescence
      but both responses were less pronounced than during HSD. Our results show two
      mitochondrial responses to hypoxia: an initial depolarization that appears to be
      caused by depressed electron transport due to lack of oxygen and a later, sudden,
      sharp depolarization linked to HSD. The depression of the second, sharp
      depolarization and the inversion of the IOS in low-chloride media suggest a role
      of Cl(-)-dependent mitochondrial swelling. Lack of effect of Ca(2+)-free medium
      on the R123 and IOS responses suggests that the protection against hypoxic damage
      by low Ca(2+) is not due to the prevention of mitochondrial depolarization.

PMID- 10899207
TI  - Modulation of responses and frequency tuning of thalamic and collicular neurons
      by cortical activation in mustached bats.
AB  - In the Jamaican mustached bat, Pteronotus parnellii parnellii, one of the
      subdivisions of the primary auditory cortex is disproportionately large and over
      represents sound at approximately 61 kHz. This area, called the Doppler-shifted
      constant frequency (DSCF) processing area, consists of neurons extremely sharply
      tuned to a sound at approximately 61 kHz. We found that a focal activation of the
      DSCF area evokes highly specific corticofugal modulation in the inferior
      colliculus and medial geniculate body. Namely a focal activation of cortical DSCF
      neurons tuned to, say, 61. 2 kHz with 0.2-ms-long, 100-nA electric pulses
      drastically increases the excitatory responses of thalamic and collicular neurons
      tuned to 61.2 kHz without shifting their best frequencies (BFs). However, it
      decreases the excitatory responses of subcortical neurons tuned to frequencies
      slightly higher or lower than 61.2 kHz and shifts their BFs away from 61.2 kHz.
      The BF shifts are symmetrical and centrifugal around 61.2 kHz. These corticofugal
      effects are larger on thalamic neurons than on collicular neurons. The cortical
      electrical stimulation sharpens the frequency-tuning curves of subcortical
      neurons. These corticofugal effects named "egocentric selection" last </=2.5 h
      after the cessation of a 7-min-long cortical electrical stimulation. In the
      mustached bat, corticofugal modulation serves to increase the contrast in neural
      representation of sound at approximately 61 kHz, which is an important component
      of an echo bearing velocity information. It is also most likely that the
      corticofugal system plays an important role in plasticity of the central auditory
      system. Another subdivision of the auditory cortex of the mustached bat is called
      the FM-FM area. This area consists of delay-tuned combination-sensitive neurons,
      called FM-FM neurons, and has the echo-delay axis for the systematic
      representation of target distances. A focal electric stimulation of the FM-FM
      area evokes changes in the responses of collicular and thalamic FM-FM neurons.
      These changes are basically the same as those described in the present paper.
      Therefore corticofugal modulation takes place for frequency domain analysis in
      exactly the same way as it does in time domain analysis.

PMID- 10899208
TI  - Learning and decay of prediction in object manipulation.
AB  - Anticipating the consequences of our own actions is a fundamental component of
      normal sensorimotor control and is seen, for example, during the manipulation of
      objects. When one hand pulls on an object held in the other hand, there is an
      anticipatory increase in grip force in the restraining hand that prevents the
      object from slipping. This anticipation is thought to rely on a forward internal
      model of the manipulated object and motor system, enabling the prediction of the
      consequences of our motor commands. Here we investigate the development of such a
      predictive response. Each hand held an object that was attached to its own torque
      motor. On each trial the subject was required to pull on the object held in the
      left hand and to maintain the position of the object held in the right hand. The
      torque motors were computer controlled so that the objects could be either
      "linked" so that the forces on the objects were equal and opposite, acting as
      though they were a single object, or "unlinked," so that they acted as two
      independent objects. A predictive response in the restraining hand is only
      necessary when the objects are linked and is unnecessary in the unlinked
      condition where there is no risk of the object slipping. To examine the learning
      and decay of predictive responses, we measured the grip force responses during
      unlinked trials that followed a linked trial. After a single linked trial,
      anticipatory grip force was quick to develop, but decayed slowly over the
      following unlinked trials. Varying the time between trials showed that the rate
      of decay depended on the number of trials since the last linked trial rather than
      time. Increasing the frequency of linked trials showed an increased level of
      subsequent grip force modulation, but did not alter the decay rate. When the
      torque motors simulated a linked object that did not have normal physical
      properties, prediction was reduced. These results show that the use of predictive
      responses has a different time course for learning and decay, and the response
      depends on experience and the physical properties of the objects.

PMID- 10899209
TI  - Multielectrode evidence for spreading activity across the superior colliculus
      movement map.
AB  - The monkey superior colliculus (SC) has maps for both visual input and movement
      output in the superficial and intermediate layers, respectively, and activity on
      these maps is generally related to visual stimuli only in one part of the visual
      field and/or to a restricted range of saccadic eye movements to those stimuli.
      For some neurons within these maps, however, activity has been reported to spread
      from the caudal SC to the rostral SC during the course of a saccade. This spread
      of activity was inferred from averages of recordings at different sites on the SC
      movement map during saccades of different amplitudes and even in different
      monkeys. In the present experiments, SC activity was recorded simultaneously in
      pairs of neurons to observe the spread of activity during individual saccades.
      Two electrodes were positioned along the rostral-caudal axis of the SC with one
      being more caudal than the other, and 60 neuron pairs whose movement fields were
      large enough to see a spread of activity were studied. During individual
      saccades, the relative time of discharge of the two neurons was compared using 1)
      the time difference between peak discharge of the two neurons, 2) the difference
      between the "median activation time" of the two neurons, and 3) the shift
      required to align the two discharge patterns using cross-correlation. All three
      analysis methods gave comparable results. Many pairs of neurons were activated in
      sequence during saccade generation, and the order of activation was most
      frequently caudal to rostral. Such a sequence of activation was not observed in
      every neuron pair, but over the sample of neuron pairs studied, the spread was
      statistically significant. When we compared the time of neuronal activity to the
      time of saccade onset, we found that the caudal neuronal activity was more likely
      to be before the saccade, whereas the rostral neuronal activity was more likely
      to be during the saccade. These results demonstrate that when individual pairs of
      neurons are examined during single saccades there is evidence of a caudal to
      rostral spread of activity within the monkey SC, and they confirm the previous
      inferences of a spread of activity drawn from observations on averaged neuronal
      activity during multiple saccades. The functional contribution of this spread of
      activity remains to be determined.

PMID- 10899210
TI  - Motor-unit synchronization is not responsible for larger motor-unit forces in old
      adults.
AB  - Motor-unit synchronization, which is a measure of the near simultaneous discharge
      of action potentials by motor units, has the potential to influence spike
      triggered average force and the steadiness of a low-force isometric contraction.
      The purpose of the study was to estimate the contribution of motor-unit
      synchronization to the larger spike-triggered average forces and the decreased
      steadiness exhibited by old adults. Eleven young (age 19-30 yr) and 14 old (age
      63-81 yr) adults participated in the study. Motor-unit activity was recorded with
      two fine-wire intramuscular electrodes in the first dorsal interosseus muscle
      during isometric contractions that caused the index finger to exert an abduction
      force. In a separate session, steadiness measurements were obtained during
      constant-force isometric contractions at target forces of 2.5, 5, 7. 5, and 10%
      of the maximum voluntary contraction (MVC) force. Mean (+/-SD) motor-unit forces
      measured by spike-triggered averaging were larger in old (15.5 +/- 12.1 mN)
      compared with young (7.3 +/- 5.7 mN) adults, and the differences were more
      pronounced between young (8.7 +/- 6.4 mN) and old (19.9 +/- 12.2 mN) men.
      Furthermore, the old adults had a reduced ability to maintain a steady force
      during an isometric contraction, particularly at low target forces (2.5 and 5%
      MVC). Mean (+/-SD) motor-unit synchronization, expressed as the frequency of
      extra synchronous discharges above chance in the cross-correlogram, was similar
      in young [0.66 +/- 0.4 impulses/s (imp/s); range, 0.35-1.51 imp/s; 53 pairs) and
      old adults (0.72 +/- 0.5 imp/s; range, 0.27-1.38 imp/s; 56 pairs). The duration
      of synchronous peaks in the cross-correlogram was similar for each group
      (approximately 16 ms). These data suggest that motor-unit synchronization is not
      responsible for larger spike-triggered average forces in old adults and that
      motor-unit synchronization does not contribute to the decreased steadiness of low
      force isometric contractions observed in old adults.

PMID- 10899211
TI  - Monosynaptic connections between identified A and B photoreceptors and
      interneurons in Hermissenda: evidence for labeled-lines.
AB  - The cellular and synaptic organization of the eye of the nudibranch mollusk
      Hermissenda is well-documented. The five photoreceptors within each eye are
      mutally inhibitory and can be classified into two types: A and B based on
      electrophysiological and anatomical criteria. Two of the three type B and two
      type A photoreceptors can be further identified according to their medial or
      lateral positions within each eye. In addition to reciprocal synaptic connections
      between photoreceptors, photoreceptors also project to second-order neurons in
      the cerebropleural ganglion. The second-order neurons receive convergent synaptic
      input from two additional sensory pathways; however, it has not been previously
      established if lateral A, lateral B, or medial B photoreceptors converge onto the
      same second-order neurons. To determine the specific synaptic organization of
      these components of the visual system, we have examined monosynaptic connections
      between identified lateral and medial type A and B photoreceptors and second
      order cerebropleural (CP) interneurons. We found that monosynaptic connections
      between identified lateral A and lateral and medial B photoreceptors and CP
      interneurons follow a labeled-line principle. Illumination of the eyes or
      extrinsic depolarizing current applied to identified photoreceptors evoked
      excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively)
      in different CP interneurons. The PSPs in CP interneurons followed one-for-one
      spikes in the photoreceptors and could be elicited in artificial seawater
      solutions containing high divalent cations. Identified photoreceptors projected
      to more than one CP interneuron and expressed both excitatory and inhibitory
      connections with the different CP interneurons. In examples where a monosynaptic
      connection between a lateral B photoreceptor and a CP interneuron was identified,
      lateral A, medial A, or medial B photoreceptors did not project to the same CP
      interneuron. Moreover, when connections between medial B and CP interneurons were
      identified, lateral A, medial A, and lateral B connections were not found to
      project to the same CP interneuron. Similar results were obtained for a lateral A
      and CP interneuron connection. These results indicate that divergent labeled
      lines exist between specific photoreceptors and second-order CP interneurons and
      potential convergence of synaptic input from primary and secondary elements of
      the visual system must occur at sites that are postsynaptic to the CP
      interneurons.

PMID- 10899212
TI  - Early components of the human vestibulo-ocular response to head rotation: latency
      and gain.
AB  - To characterize vestibulo-ocular reflex (VOR) properties in the time window in
      which contributions by other systems are minimal, eye movements during the first
      50-100 ms after the start of transient angular head accelerations ( approximately
      1000 degrees /s(2)) imposed by a torque helmet were analyzed in normal human
      subjects. Orientations of the head and both eyes were recorded with magnetic
      search coils (resolution, approximately 1 min arc; 1000 samples/s). Typically,
      the first response to a head perturbation was an anti-compensatory eye movement
      with zero latency, peak-velocity of several degrees per second, and peak
      excursion of several tenths of a degree. This was interpreted as a passive
      mechanical response to linear acceleration of the orbital tissues caused by
      eccentric rotation of the eye. The response was modeled as a damped oscillation
      (approximately 13 Hz) of the orbital contents, approaching a constant eye
      deviation for a sustained linear acceleration. The subsequent compensatory eye
      movements showed (like the head movements) a linear increase in velocity, which
      allowed estimates of latency and gain with linear regressions. After appropriate
      accounting for the preceding passive eye movements, average VOR latency (for
      pooled eyes, directions, and subjects) was calculated as 8.6 ms. Paired
      comparisons between the two eyes revealed that the latency for the eye
      contralateral to the direction of head rotation was, on average, 1.3 ms shorter
      than for the ipsilateral eye. This highly significant average inter-ocular
      difference was attributed to the additional internuclear abducens neuron in the
      pathway to the ipsilateral eye. Average acceleration gain (ratio between slopes
      of eye and head velocities) over the first 40-50 ms was approximately 1.1.
      Instantaneous velocity gain, calculated as Veye(t)/Vhead(t-latency), showed a
      gradual build-up converging toward unity (often after a slight overshoot).
      Instantaneous acceleration gain also converged toward unity but showed a much
      steeper build-up and larger oscillations. This behavior of acceleration and
      velocity gain could be accounted for by modeling the eye movements as the sum of
      the passive response to the linear acceleration and the active rotational VOR.
      Due to the latency and the anticompensatory component, gaze stabilization was
      never complete. The influence of visual targets was limited. The initial VOR was
      identical with a distant target (continuously visible or interrupted) and in
      complete darkness. A near visual target caused VOR gain to rise to a higher
      level, but the time after which the difference between far and near targets
      emerged varied between individuals.

PMID- 10899213
TI  - Intracellular features predicted by extracellular recordings in the hippocampus
      in vivo.
AB  - Multichannel tetrode array recording in awake behaving animals provides a
      powerful method to record the activity of large numbers of neurons. The power of
      this method could be extended if further information concerning the intracellular
      state of the neurons could be extracted from the extracellularly recorded
      signals. Toward this end, we have simultaneously recorded intracellular and
      extracellular signals from hippocampal CA1 pyramidal cells and interneurons in
      the anesthetized rat. We found that several intracellular parameters can be
      deduced from extracellular spike waveforms. The width of the intracellular action
      potential is defined precisely by distinct points on the extracellular spike.
      Amplitude changes of the intracellular action potential are reflected by changes
      in the amplitude of the initial negative phase of the extracellular spike, and
      these amplitude changes are dependent on the state of the network. In addition,
      intracellular recordings from dendrites with simultaneous extracellular
      recordings from the soma indicate that, on average, action potentials are
      initiated in the perisomatic region and propagate to the dendrites at 1.68 m/s.
      Finally we determined that a tetrode in hippocampal area CA1 theoretically should
      be able to record electrical signals from approximately 1, 000 neurons. Of these,
      60-100 neurons should generate spikes of sufficient amplitude to be detectable
      from the noise and to allow for their separation using current spatial clustering
      methods. This theoretical maximum is in contrast to the approximately six units
      that are usually detected per tetrode. From this, we conclude that a large
      percentage of hippocampal CA1 pyramidal cells are silent in any given behavioral
      condition.

PMID- 10899214
TI  - Accuracy of tetrode spike separation as determined by simultaneous intracellular
      and extracellular measurements.
AB  - Simultaneous recording from large numbers of neurons is a prerequisite for
      understanding their cooperative behavior. Various recording techniques and spike
      separation methods are being used toward this goal. However, the error rates
      involved in spike separation have not yet been quantified. We studied the
      separation reliability of "tetrode" (4-wire electrode)-recorded spikes by
      monitoring simultaneously from the same cell intracellularly with a glass pipette
      and extracellularly with a tetrode. With manual spike sorting, we found a trade
      off between Type I and Type II errors, with errors typically ranging from 0 to
      30% depending on the amplitude and firing pattern of the cell, the similarity of
      the waveshapes of neighboring neurons, and the experience of the operator.
      Performance using only a single wire was markedly lower, indicating the
      advantages of multiple-site monitoring techniques over single-wire recordings.
      For tetrode recordings, error rates were increased by burst activity and during
      periods of cellular synchrony. The lowest possible separation error rates were
      estimated by a search for the best ellipsoidal cluster shape. Human operator
      performance was significantly below the estimated optimum. Investigation of error
      distributions indicated that suboptimal performance was caused by inability of
      the operators to mark cluster boundaries accurately in a high-dimensional feature
      space. We therefore hypothesized that automatic spike-sorting algorithms have the
      potential to significantly lower error rates. Implementation of a semi-automatic
      classification system confirms this suggestion, reducing errors close to the
      estimated optimum, in the range 0-8%.

PMID- 10899215
TI  - Physiological activation of presynaptic metabotropic glutamate receptors
      increases intracellular calcium and glutamate release.
AB  - Activation of metabotropic glutamate receptors (mGluRs) has diverse effects on
      the functioning of vertebrate synapses. The cellular mechanisms that underlie
      these changes, however, are largely unknown. The role of presynaptic mGluRs in
      modulating Ca(2+) dynamics and regulating neurotransmitter release was
      investigated at the vestibulospinal-reticulospinal (VS-RS) synapse in the lamprey
      brain stem. Application of the specific Group I mGluRs antagonist 7
      (hydroxyimino) cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) reduced
      the amplitude of consecutive high-frequency evoked excitatory postsynaptic
      currents (EPSCs). A series of experiments using techniques of electrophysiology
      and calcium imaging were carried out to determine the cellular mechanisms by
      which this phenomenon occurs. Concentration-dependent increases in the pre- and
      postsynaptic [Ca(2+)](i) were seen with the application of mGluR agonists.
      Similarly, high-frequency stimulation of axons caused a Group I mGluR-dependent
      enhancement in presynaptic Ca(2+) transients. Application of mGluR agonist caused
      a depolarization of the presynaptic elements, while thapsigargin decreased the
      high-frequency stimulus- and agonist-induced rises in [Ca(2+)](i). These data
      suggest that both membrane depolarization and the release of Ca(2+) from
      intracellular stores potentially play a role in mGluR-induced Ca(2+) signaling.
      To determine the effect of this modulation of Ca(2+) dynamics on spontaneous
      glutamate release, miniature EPSCs were recorded from postsynaptic reticulospinal
      neurons. A potent Group I mGluR agonist, (S)-homoquisqualic acid, caused a large
      increase in the frequency of events. These results demonstrate the presence of
      presynaptic Group I mGluRs at the VS-RS synapse. Activation of these receptors
      leads to a rise in [Ca(2+)](i) and enhances the spontaneous and evoked release of
      glutamate. Taken together, these studies highlight the importance of synaptic
      activation of these facilitatory autoreceptors in both short-term plasticity and
      synaptic transmission.

PMID- 10899216
TI  - An excitatory GABAergic plexus in developing neocortical layer 1.
AB  - Layer 1 of the developing rodent somatosensory cortex contains a dense, transient
      GABAergic fiber plexus. Axons arising from the zona incerta (ZI) of the ventral
      thalamus contribute to this plexus, as do axons of intrinsic GABAergic cells of
      layer 1. The function of this early-appearing fiber plexus is not known, but
      these fibers are positioned to contact the apical dendrites of most postmigratory
      neurons. Here we show that electrical stimulation of layer 1 results in a GABA(A)
      mediated postsynaptic current (PSC) in pyramidal neurons. Gramicidin perforated
      patch recording demonstrates that the GABAergic layer 1 synapse is excitatory and
      can trigger action potentials in cortical neurons. In contrast to electrical
      stimulation, activation of intrinsic layer 1 neurons with a glutamate agonist
      fails to produce PSCs in pyramidal cells. In addition, responses can be evoked by
      stimulation of layer 1 at relatively large distances from the recording site.
      These findings are consistent with a contribution of the widely projecting
      incertocortical pathway, the only described GABAergic projection to neonatal
      cortex. Recording of identified neonatal incertocortical neurons reveals a
      population of active cells that exhibit high frequencies of spontaneous action
      potentials and are capable of robustly activating neonatal cortical neurons.
      Because the fiber plexus is confined to layer 1, this pathway provides a
      spatially restricted excitatory GABAergic innervation of the distal apical
      dendrites of pyramidal neurons during the peak period of cortical synaptogenesis.

PMID- 10899217
TI  - Directional sensitivity of neurons in the primary auditory (AI) cortex of the cat
      to successive sounds ordered in time and space.
AB  - Two transient sounds, considered as a conditioner followed by a probe, were
      delivered successively from the same or different direction in virtual acoustic
      space (VAS) while recording from single neurons in primary auditory cortex (AI)
      of cats under general anesthesia. Typically, the response to the probe sound was
      progressively suppressed as the interval between the two sounds (ISI) was
      systematically reduced from 400 to 50 ms, and the sound-source directions were
      within the cell's virtual space receptive field (VSRF). Suppression of the cell's
      discharge could be accompanied by an increase in response latency. In some
      neurons, the joint response to two sounds delivered successively was summative or
      facilitative at ISIs below about 20 ms. These relationships held throughout the
      VSRF, including those directions on or near the cell's acoustic axis where sounds
      often elicit the strongest response. The strength of suppression varied
      systematically with the direction of the probe sound when the ISI was fixed and
      the conditioning sound arrived from the cell's acoustic axis. Consequently a VSRF
      defined by the response to the lagging probe sound was progressively reduced in
      size when ISIs were shortened from 400 to 50 ms. Although the presence of a
      previous sound reduced the size of the VSRF, for many of these VSRFs a systematic
      gradient of response latency was maintained. The maintenance of such a gradient
      may provide a mechanism by which directional acuity remains intact in an acoustic
      environment containing competing acoustic transients.

PMID- 10899218
TI  - Task-specific neural activity in the primate prefrontal cortex.
AB  - Real-world behavior is typically more complicated than a one-to-one mapping
      between a stimulus and response; the same stimulus can lead to different
      behaviors depending on the situation, or the same behavior may be cued by
      different stimuli. In such cases, knowledge of the formal demands of the task at
      hand is required. We found that in monkeys trained to alternate between three
      tasks, the activity of many neurons in the prefrontal cortex was task dependent.
      This included changes in overall firing rate, in firing-rate profiles (shape of
      responses over time), and in stimulus and response selectivity. These findings
      support the hypothesis that a major prefrontal function is the acquisition and
      implementation of task context and the "rules" used to guide behavior.

PMID- 10899219
TI  - Contribution of superficial layer neurons to premotor bursts in the superior
      colliculus.
AB  - In vitro whole-cell patch-clamp methods were used to examine the contribution of
      one component of intracollicular circuitry, the superficial gray layer, to the
      generation of bursts of action potentials that occur in the intermediate layer
      and that command head and eye movements in vivo. Applying a single brief (0.5 ms)
      pulse of current to the superficial layer of rat collicular slices evoked
      prolonged bursts of excitatory postsynaptic currents (EPSCs) in the cells of the
      intermediate layer. The EPSCs were sufficient to elicit bursts of action
      potentials that lasted as long as 300 ms and resembled presaccadic command
      bursts. To examine the contribution of neurons within the superficial layer to
      the production of these bursts, we determined how superficial neurons respond to
      the same current pulses that evoke bursts in the intermediate layer. Recordings
      from 61 superficial layer cells revealed 19 neurons that produced multiple action
      potentials following stimulation. Nine of these 19 neurons were wide- and narrow
      field vertical cells, which are known to project to the intermediate layer and
      could contribute to producing the EPSC bursts. The remaining cells (n = 42) did
      not generate trains of action potentials and 21 of these showed only subthreshold
      potential changes in response to the stimulus. Our results indicate that most
      superficial cells do not directly contribute to production of the EPSC bursts,
      but a small number do have the properties necessary to provide a prolonged
      excitatory drive to the premotor neurons.

PMID- 10899221
TI  - Segregation of nociceptive and non-nociceptive networks in the squirrel monkey
      somatosensory thalamus.
AB  - The somatosensory thalamus (here we examine neurons in the caudal cutaneous
      portion of ventral posterior lateral nucleus, VPL) is composed of a somatotopic
      arrangement of anteroposteriorly oriented rods. Each rod is a collection of
      neurons with homogeneous properties that relay sensory information to specific
      cortical columns. We developed a multi-electrode recording technique, using fixed
      geometry four-tip electrodes that allow simultaneous recordings from small
      populations of neurons (4-11), in a approximately 150 x 150 x 150 micrometer(3)
      volume of brain tissue (i.e., the approximate diameter of rods) and study of
      their spatiotemporal interactions. Due to the fixed geometry of the four-tip
      electrodes, the relative locations of these neurons can be determined, and due to
      the simultaneity of the recordings, their spike-timing coordination can be
      calculated. With this method, we demonstrate the existence of two distinct
      functional networks: nociceptive and non-nociceptive networks. The population
      dynamics of these two types of networks are different: cross-correlations in each
      type of network were different in direction and strength, were a function of the
      distance between neurons, had an opponent organization for nociceptive networks
      and a non-opponent organization for non-nociceptive networks, and rapidly changed
      under different stimulus conditions independent of changes in firing rates. A
      simple neural network model mimicked these physiological findings, demonstrating
      the necessity of inhibitory interneurons and different amounts of afferent input
      synchronization. Based on these results, we conclude that the somatosensory
      thalamus is composed of two modules, nociceptive and non-nociceptive rods, and
      that the response dynamics differences between these modules are due to
      spatiotemporal differences of their afferent inputs.

PMID- 10899220
TI  - BDNF-Induced potentiation of spontaneous twitching in innervated myocytes
      requires calcium release from intracellular stores.
AB  - Brain-derived neurotrophic factor (BDNF) can potentiate synaptic release at newly
      developed frog neuromuscular junctions. Although this potentiation depends on
      extracellular Ca(2+) and reflects changes in acetylcholine release, little is
      known about the intracellular transduction or calcium signaling pathways. We have
      developed a video assay for neurotrophin-induced potentiation of myocyte
      twitching as a measure of potentiation of synaptic activity. We use this assay to
      show that BDNF-induced synaptic potentiation is not blocked by cadmium,
      indicating that Ca(2+) influx through voltage-gated Ca(2+) channels is not
      required. TrkB autophosphorylation is not blocked in Ca(2+)-free conditions,
      indicating that TrkB activity is not Ca(2+) dependent. Additionally, an inhibitor
      of phospholipase C interferes with BDNF-induced potentiation. These results
      suggest that activation of the TrkB receptor activates phospholipase C to
      initiate intracellular Ca(2+) release from stores which subsequently potentiates
      transmitter release.

PMID- 10899222
TI  - Simulated seizures and spreading depression in a neuron model incorporating
      interstitial space and ion concentrations.
AB  - Sustained inward currents in neuronal membranes underlie tonic-clonic seizure
      discharges and spreading depression (SD). It is not known whether these currents
      flow through abnormally operating physiological ion channels or through
      pathological pathways that are not normally present. We have now used the NEURON
      simulating environment of Hines, Moore, and Carnevale to model seizure discharges
      and SD. The geometry and electrotonic properties of the model neuron conformed to
      a hippocampal pyramidal cell. Voltage-controlled transient and persistent sodium
      currents (I(Na,T) and I(Na,P)), potassium currents (I(K,DR) and I(K,A)), and N
      methyl-D-aspartate (NMDA) receptor-controlled currents (I(NMDA)), were inserted
      in the appropriate regions of the model cell. The neuron was surrounded by an
      interstitial space where extracellular potassium and sodium concentration
      ([K(+)](o) and [Na(+)](o)) could rise or fall. Changes in intra- and
      extracellular ion concentrations and the resulting shifts in the driving force
      for ionic currents were continuously computed based on the amount of current
      flowing through the membrane. A Na-K exchange pump operated to restore ion
      balances. In addition, extracellular potassium concentration, [K(+)](o), was also
      controlled by a "glial" uptake function. Parameters were chosen to resemble
      experimental data. As long as [K(+)](o) was kept within limits by the activity of
      the Na-K pump and the "glial" uptake, a depolarizing current pulse applied to the
      cell soma evoked repetitive firing that ceased when the stimulating current
      stopped. If, however, [K(+)](o) was allowed to rise, then a brief pulse provoked
      firing that outlasted the stimulus. At the termination of such a burst, the cell
      hyperpolarized and then slowly depolarized and another burst erupted without
      outside intervention. Such "clonic" bursting could continue indefinitely
      maintained by an interplay of the rise and fall of potassium and sodium
      concentrations with membrane currents and threshold levels. SD-like
      depolarization could be produced in two ways, 1) by a dendritic NMDA-controlled
      current. Glutamate was assumed to be released in response to rising [K(+)](o).
      And 2) by the persistent (i.e., slowly inactivating) Na-current, I(Na,P). When
      both I(NMDA) and I(Na,P) were present, the two acted synergistically. We conclude
      that epileptiform neuronal behavior and SD-like depolarization can be generated
      by the feedback of ion currents that change ion concentrations, which, in turn,
      influence ion currents and membrane potentials. The normal stability of brain
      function must depend on the efficient control of ion activities, especially that
      of [K(+)](o).

PMID- 10899223
TI  - Altered calcium homeostasis in cerebellar Purkinje cells of leaner mutant mice.
AB  - The leaner (tg(la)) mouse mutation occurs in the gene encoding the voltage
      activated Ca(2+) channel alpha(1A) subunit, the pore-forming subunit of P/Q-type
      Ca(2+) channels. This mutation results in dramatic reductions in P-type Ca(2+)
      channel function in cerebellar Purkinje neurons of tg(la)/tg(la) mice that could
      affect intracellular Ca(2+) signaling. We combined whole cell patch-clamp
      electrophysiology with fura-2 microfluorimetry to examine aspects of Ca(2+)
      homeostasis in acutely dissociated tg(la)/tg(la) Purkinje cells. There was no
      difference between resting somatic Ca(2+) concentrations in tg(la)/tg(la) cells
      and in wild-type (+/+) cells. However, by quantifying the relationship between
      intracellular Ca(2+) elevations and depolarization-induced Ca(2+) influx, we
      detected marked alterations in rapid calcium buffering between the two genotypes.
      Calcium buffering values (ratio of bound/free ions) were significantly reduced in
      tg(la)/tg(la) (584 +/- 52) Purkinje cells relative to +/+ (1,221 +/- 80) cells.
      By blocking the endoplasmic reticulum (ER) Ca(2+)-ATPases with thapsigargin, we
      observed that the ER had a profound impact on rapid Ca(2+) buffering that was
      also differential between tg(la)/tg(la) and +/+ Purkinje cells. Diminished Ca(2+)
      uptake by the ER apparently contributes to the reduced buffering ability of
      mutant cells. This report constitutes one of the few instances in which the ER
      has been implicated in rapid Ca(2+) buffering. Concomitant with this reduced
      buffering, in situ hybridization with calbindin D28k and parvalbumin antisense
      oligonucleotides revealed significant reductions in mRNA levels for these Ca(2+)
      binding proteins (CaBPs) in tg(la)/tg(la) Purkinje cells. All of these results
      suggest that alterations of Ca(2+) homeostasis in tg(la)/tg(la) mouse Purkinje
      cells may serve as a mechanism whereby reduced P-type Ca(2+) channel function
      contributes to the mutant phenotype.

PMID- 10899224
TI  - Selective opiate modulation of nociceptive processing in the human brain.
AB  - Fentanyl, a mu-opioid receptor agonist, produces analgesia while leaving
      vibrotactile sensation intact. We used positron emission tomography (PET) to
      study the mechanisms mediating this specific effect in healthy, right-handed
      human males (ages 18-28 yr). Subjects received either painful cold (n = 11) or
      painless vibratory (n = 9) stimulation before and after the intravenous injection
      of fentanyl (1.5 microgram/kg) or placebo (saline). Compared with cool water (29
      degrees C), immersion of the hand in ice water (1 degrees C) is painful and
      produces highly significant increases in regional cerebral blood flow (rCBF)
      within the contralateral second somatosensory (S2) and insular cortex,
      bilaterally in the thalamus and cerebellum, and medially in the cerebellar
      vermis. Responses just below the statistical threshold (3.5 < Z < 4.0) are seen
      in the contralateral anterior cingulate, ipsilateral insular cortex, and dorsal
      medial midbrain. The contralateral primary sensory cortex (S1) shows a trend of
      activation. Except for slight changes in intensity, this pattern is unchanged
      following a saline placebo injection. Fentanyl reduces the average visual
      analogue scale ratings of perceived pain intensity (47%) and unpleasantness
      (50%), reduces pain-related cardioacceleration, and has positive hedonic effects.
      After fentanyl, but not placebo, all cortical and subcortical responses to
      noxious cold are greatly reduced. Subtraction analysis [(innocuous water +
      fentanyl) - (innocuous water + no injection)] shows that fentanyl alone increases
      rCBF in the anterior cingulate cortex, particularly in the perigenual region.
      Vibration (compared with mock vibration) evokes highly significant rCBF responses
      in the contralateral S1 cortex in the baseline (no injection) and placebo
      conditions; borderline responses (3.5 < Z < 4. 0) are detected also in the
      contralateral thalamus. Fentanyl has no effect on the perceived intensity or
      unpleasantness of vibratory stimulation, which continues to activate
      contralateral S1. Fentanyl alone [(mock vibration + fentanyl) - (mock vibration +
      no injection)] again produces highly significant activation of the perigenual and
      mid-anterior cingulate cortex. A specific comparison of volumes of interest,
      developed from activation peaks in the baseline condition (no injection), shows
      that fentanyl strongly attenuates both the contralateral thalamic and S1 cortical
      responses to noxious cold stimulation (P < 0.048 and 0.007, respectively) but
      fails to affect significantly these responses to vibrotactile stimulation (P >
      0.26 and 0.91, respectively). In addition, fentanyl, compared with placebo,
      produces a unique activation of the mid-anterior cingulate cortex during fentanyl
      analgesia, suggesting that this region of the cingulate cortex participates
      actively in mediating opioid analgesia. The results are consistent with a
      selective, fentanyl-mediated suppression of nociceptive spinothalamic
      transmission to the forebrain. This effect could be implemented directly at the
      spinal level, indirectly through cingulate corticofugal pathways, or by a
      combination of both mechanisms.

PMID- 10899225
TI  - Immunocytochemical and physiological characterization of a population of cultured
      human neural precursors.
AB  - Human neural precursor cells (HNPC) have recently become commercially available.
      In an effort to determine the usefulness of these cells for in vitro studies, we
      have grown cultured HNPCs (cHNPCs) according to the supplier specifications. Here
      we report our characterization of cHNPCs under nondifferentiating and
      differentiating growth conditions and make a comparison to primary HNPCs (pHNPCs)
      obtained at the same developmental time point from a different commercial
      supplier. We found that under nondifferentiating conditions, cHNPCs expressed
      nestin, divided rapidly, expressed few markers of differentiated cells, and
      displayed both 4-aminopyridine (4-AP)-sensitive and delayed-rectifier type K(+)
      currents. No inward currents were observed. On changing to differentiating
      culture conditions, a majority of the cells expressed neuronal markers, did not
      divide, expressed inward and outward time- and voltage-dependent currents, and
      responded to the application of the neurotransmitters acetylcholine and
      glutamate. The outward current densities were indistinguishable from those in
      undifferentiated cells. The inward currents included TTX-sensitive and -resistant
      Na(+) currents, sustained Ca(2+) currents, and an inwardly rectifying K(+)
      current. Comparison of the properties of differentiated cells from cHNPCs with
      neurons obtained from primary fetal cultures (pHNPCs) revealed two major
      differences: the differentiated cHNPCs did not express embryonic neural cell
      adhesion molecule (E-NCAM) immunoreactivity but did co-express GFAP
      immunoreactivity. The co-expression of neuronal and glial markers was likely due
      to the growth of cells in serum containing medium as the pHNPCs that were never
      exposed to serum did express E-NCAM and did not co-express glial fibrillary
      acidic protein (GFAP). The relevance of these results is discussed and compared
      with results from other neuronal progenitor populations and cultured human
      neuronal cells.

PMID- 10899226
TI  - Dopamine D(1) agonist activates temporal lobe structures in primates.
AB  - Changes in the function of dopamine D(1)-influenced neuronal pathways may be
      important to the pathophysiology of several human diseases. We recently developed
      methods for averaging functional imaging data across nonhuman primate subjects;
      in this study, we apply this method for the first time to map brain responses to
      experimental dopamine agonists in vivo. Here we report the use of positron
      emission tomography (PET) in seven normal baboons to measure the regional
      cerebral blood flow (rCBF) responses produced by an acute dose of the dopamine
      D(1) full agonist SKF82958. The most significant rCBF increases were in bilateral
      temporal lobe, including amygdala and superior temporal sulcus (6-17%, P <
      0.001). Blood flow decreased in thalamus, pallidum, and pons (4-7%, P = 0.001).
      Furthermore the rCBF responses were dose-dependent and had a half-life of
      approximately 30 min, similar to that reported for the drug's antiparkinsonian
      effects. Absolute whole-brain blood flow did not change, suggesting that these
      local changes in rCBF reflect neuronal rather than direct vascular effects of the
      agonist. The prominent temporal lobe response to a D(1) agonist supports and
      extends our recent observations that levodopa produces prominent amygdala
      activation both in humans and in other primates. We speculate that levodopa may
      exert its known effects on mood in humans through increased amygdala activity,
      mediated in part by D(1) receptors.

PMID- 10899227
TI  - Segregation of somatosensory activation in the human rolandic cortex using fMRI.
AB  - The segregation of sensory information into distinct cortical areas is an
      important organizational feature of mammalian sensory systems. Here, we provide
      functional magnetic resonance imaging (fMRI) evidence for the functional
      delineation of somatosensory representations in the human central sulcus region.
      Data were collected with a 3-Tesla scanner during two stimulation protocols, a
      punctate tactile condition without a kinesthetic/motor component, and a
      kinesthetic/motor condition without a punctate tactile component. With three
      dimensional (3-D) anatomical reconstruction techniques, we analyzed data in
      individual subjects, using the pattern of activation and the anatomical position
      of specific cortical areas to guide the analysis. As a complimentary analysis, we
      used a brain averaging technique that emphasized the similarity of cortical
      features in the morphing of individual subjects and thereby minimized the
      distortion of the location of cortical activation sites across individuals. A
      primary finding of this study was differential activation of the cortex on the
      fundus of the central sulcus, the position of area 3a, during the two tasks.
      Punctate tactile stimulation of the palm, administered at 3 Hz with a
      5.88(log10.mg) von Frey filament, activated discrete regions within the
      precentral (PreCG) and postcentral (PoCG) gyri, corresponding to areas 6, 3b, 1,
      and 2, but did not activate area 3a. Conversely, kinesthetic/motor stimulation, 3
      Hz flexion and extension of the digits, activated area 3a, the PreCG (areas 6 and
      4), and the PoCG (areas 3b, 1, and 2). These activation patterns were observed in
      individual subjects and in the averaged data, providing strong evidence for the
      existence of a distinct representation within area 3a in humans. The percentage
      signal changes in the PreCG and PoCG regions activated by tactile stimulation,
      and in the intervening gap region, support this functional dissociation. In
      addition to this distinction within the fundus of the central sulcus, the
      combination of high-resolution imaging and 3-D analysis techniques permitted
      localization of activation within areas 6, 4, 3a, 3b, 1, and 2 in the human. With
      the exception of area 4, which showed inconsistent activation during punctate
      tactile stimulation, activation in these areas in the human consistently
      paralleled the pattern of activity observed in previous studies of monkey cortex.

PMID- 10899228
TI  - Microstimulation-induced inhibition of neuronal firing in human globus pallidus.
AB  - Neurosurgical treatment of Parkinson's disease (PD) frequently employs chronic
      high-frequency deep brain stimulation (DBS) within the internal segment of globus
      pallidus (GPi) and can very effectively reduce L-dopa-induced dyskinesias and
      bradykinesia, but the mechanisms are unknown. The present study examined the
      effects of microstimulation in GPi on the activity of neurons close to the
      stimulation site. Recordings were made from GPi using two fixed or independently
      controlled microelectrodes, with the electrode tips usually approximately 250 or
      >600 micrometer apart in PD patients undergoing stereotactic exploration to
      localize the optimal site for placement of a lesion or DBS electrode. The
      spontaneous activity of nearly all of the cells (22/23) recorded in GPi in three
      patients was inhibited by microstimulation at currents typically <10 microA (0.15
      ms pulses at 5 Hz). The inhibition had a duration of 10-25 ms at threshold. These
      findings suggest that microstimulation within GPi preferentially excites the axon
      terminals of striatal and/or external pallidal neurons causing release of GABA
      and inhibition of GPi neurons.

PMID- 10899229
TI  - Blocking adenylyl cyclase inhibits olfactory generator currents induced by "IP(3)
      odors".
AB  - Vertebrate olfactory receptor neurons (ORNs) transduce odor stimuli into
      electrical signals by means of an adenylyl cyclase/cAMP second messenger cascade,
      but it remains widely debated whether this cAMP cascade mediates transduction for
      all odorants or only certain odor classes. To address this problem, we have
      analyzed the generator currents induced by odors that failed to produce cAMP in
      previous biochemical assays but instead produced IP(3) ("IP(3)-odors"). We show
      that in single salamander ORNs, sensory responses to "cAMP-odors" and IP(3)-odors
      are not mutually exclusive but coexist in the same cells. The currents induced by
      IP(3)-odors exhibit identical biophysical properties as those induced by cAMP
      odors or direct activation of the cAMP cascade. By disrupting adenylyl cyclase to
      block cAMP formation using two potent antagonists of adenylyl cyclase, SQ22536
      and MDL12330A, we show that this molecular step is necessary for the transduction
      of both odor classes. To assess whether these results are also applicable to
      mammals, we examine the electrophysiological responses to IP(3)-odors in intact
      mouse main olfactory epithelium (MOE) by recording field potentials. The results
      show that inhibition of adenylyl cyclase prevents EOG responses to both odor
      classes in mouse MOE, even when "hot spots" with heightened sensitivity to IP(3)
      odors are examined.

PMID- 10899230
TI  - Expansion of afferent vestibular signals after the section of one of the
      vestibular nerve branches.
AB  - The anterior branch of N. VIII was sectioned in adult frogs. Two months later the
      brain was isolated to record in vitro responses in the vestibular nuclei and from
      the abducens nerves following electric stimulation of the anterior branch of N.
      VIII or of the posterior canal nerve. Extra- and intracellularly recorded
      responses from the intact and operated side were compared with responses from
      controls. Major changes were detected on the operated side: the amplitudes of
      posterior canal nerve evoked field potentials were enlarged, the number of
      vestibular neurons with a monosynaptic input from the posterior canal nerve had
      increased, and posterior canal nerve stimulation recruited stronger abducens
      nerve responses on the intact side than vice versa. Changes in the convergence
      pattern of vestibular nerve afferent inputs on the operated side strongly suggest
      the expansion of posterior canal-related afferent inputs onto part of those
      vestibular neurons that were deprived of their afferent vestibular input. As a
      mechanism we suggest reactive synaptogenesis between intact posterior canal
      afferent fibers and vestibularly deprived second-order vestibular neurons.

PMID- 10899231
TI  - Functional connectivity between cerebellum and primary motor cortex in the awake
      monkey.
AB  - Simultaneous single neuron and local field potential (LFP) recordings were made
      in arm-related areas of the cerebellar nuclei (CN) and primary motor cortex (M1)
      of two monkeys during a reaching and button pressing task. Microstimulation of
      focal sites in CN caused short latency (median = 3.0 ms) increases in discharge
      in 25% of 210 M1 neurons. Suppressive effects were less common (13%) and observed
      at longer latencies (median = 9.9 ms). Stimulation in CN also caused reciprocal
      facilitation and suppression in averages of antagonist muscle electromyograms
      (EMGs). The latency of these effects was approximately 8-11 ms. In contrast to
      the selectivity of unit and EMG effects, stimulation-evoked changes in LFP
      occurred over a broad range of sites. There were no significant short-latency
      effects detected in cross-correlation histograms between single neurons in CN and
      M1. However, CN spike-triggered averages of M1 LFPs were observed in a few cases
      (10% of 126 cases). In one-half of these, there were effects both before and
      after the CN spikes, which may reflect causal effects from M1 to CN, as well as
      from CN to M1. Overall, these results demonstrate a spatially specific, short
      latency, primarily excitatory pathway from CN to M1. The relatively rare effects
      at the single neuron level may have resulted from the difficulty in achieving
      optimal alignment between cerebellar and cerebral sites because of the
      specificity of these connections.

PMID- 10899232
TI  - Embryonic cord transplants in peripheral nerve restore skeletal muscle function.
AB  - The rapid atrophy of skeletal muscle after denervation severely compromises
      efforts to restore muscle function. We have transplanted embryonic day 14-15 (E14
      E15) ventral spinal cord cells into adult Fischer rat tibial nerve stump to
      provide neurons for reinnervation. Our aim was to evaluate medial gastrocnemius
      reinnervation physiologically because this transplant strategy will only be
      effective if the reinnervated muscle contracts, generates sufficient force to
      induce joint movement, and is fatigue resistant enough to shorten repeatedly.
      Twelve weeks posttransplantation, brief duration electrical stimuli applied to
      the transplants induced medial gastrocnemius contractions that were strong enough
      to produce ankle movement in 4 of 12 rats (33%). The force of these four "low
      threshold" reinnervated muscles and control muscles declined only gradually
      during five hours of intermittent, supramaximal stimulation and without
      depression of EMG potential area, which is strong evidence of functional
      neuromuscular junctions and fatigue resistant muscles. Sectioning of the medial
      gastrocnemius nerves confirmed that these contractions were innervation
      dependent. Weakness in low-threshold reinnervated muscles (8% control force)
      related to incomplete reinnervation, reductions in muscle fiber size, specific
      tension, and/or the presence of nonfunctional neuromuscular junctions. Muscle
      reinnervation achieved using this novel transplantation strategy may salvage
      completely denervated muscle and may provide the potential to evoke limb movement
      when injury or disease precludes or delays peripheral axon regeneration.

PMID- 10899233
TI  - Transition to endogenous bursting after long-term decentralization requires De
      novo transcription in a critical time window.
AB  - Rhythmic motor pattern generation by the pyloric network in the lobster
      stomatogastric ganglion (STG) requires neuromodulatory inputs from adjacent
      ganglia. However, although suppression of these inputs by cutting the
      stomatogastric nerve (stn) causes the pyloric network to fall silent, network
      output similar to that expressed when the stn is intact returns after 3-4 days in
      organ culture. Intracellular recordings from identified pyloric dilator (PD)
      neurons indicate that the fundamental change underlying rhythm recovery resides
      with the intrinsic excitability of pyloric neurons themselves, since the
      prolonged absence of extrinsic modulatory inputs allows the expression of an
      endogenous oscillatory capability that is maintained in a strictly conditional
      state when these inputs are present. To examine whether gene transcription was
      involved in this change in neuronal behavior, we performed in vitro experiments
      in which the STG was exposed to the RNA-synthesis inhibitor actinomycin D (ACD).
      ACD (50 microM) incubation at the time of decentralization prevented subsequent
      reacquisition of PD neuron bursting, but the inhibitor was much less effective
      when applied at later postdecentralization times, suggesting that the recovery
      process arises from new protein synthesis triggered when modulatory inputs are
      first removed. Moreover, in the nondecentralized STG, trans-synaptic modulatory
      instruction may sustain the conditional pyloric network phenotype by continuously
      regulating expression of genes responsible for intrinsic neuronal rhythmogenesis.

PMID- 10899235
TI  - Charles E. Culpeper scholarships in medical science

PMID- 10899234
TI  - Intact functional inhibition in the surround of experimentally induced focal
      cortical dysplasias in rats.
AB  - Early postnatal injections of ibotenate into the rat neopallium induce cortical
      dysplasias mimicking human polymicrogyria which often goes along with seizure
      disorders. Under in vitro conditions these experimentally induced dysplasias
      cause widespread hyperexcitability. The underlying mechanisms are as yet not
      fully understood. Electrophysiologically there is clear evidence of widespread
      alterations of the excitatory system. Intracellular recordings also showed some
      changes of the inhibitory system but have concentrated on recordings from focal
      areas close to the microgyrus. We investigated the integrity of functional
      inhibition using a paired-pulse paradigm to map the whole ipsilateral hemisphere.
      In rat cortical slices double-pulses were applied in layer VI/white matter and
      field potentials recorded in layer II/III. The ratio of the field potential
      amplitude did not show significant alterations in the dysplasias or their
      surround as compared with control and sham-injected animals. This result was
      obtained with two different locations of the dysplasias, excluding a mere areal
      specific effect. Our results show that despite prominent hyperexcitability in the
      surround of ibotenate-induced cortical dysplasias the inhibitory network appears
      to be functionally intact.

PMID- 10899236
TI  - The heterogeneity of chronic obstructive pulmonary disease.

PMID- 10899237
TI  - Respiratory antibiotic use and clostridium difficile infection: is it the drugs
      or is it the doctors?

PMID- 10899238
TI  - Physiological and radiological characterisation of patients diagnosed with
      chronic obstructive pulmonary disease in primary care.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common although often
      poorly characterised, particularly in primary care. However, application of
      guidelines to the management of such patients needs a clear understanding of the
      phenotype. In particular, the British guidelines for the management of COPD
      recommend that the diagnosis is based on appropriate symptoms and evidence of
      airflow obstruction as determined by a forced expiratory volume in one second
      (FEV(1)) of <80% of the predicted value and an FEV(1)/VC ratio of <70%. METHODS:
      A study was undertaken of 110 patients aged 40-80 years who had presented to
      their general practitioner with an acute exacerbation of COPD. The episode was
      treated at home and, when patients had recovered to the stable state (two months
      later), they were characterised by full lung function tests and a high resolution
      computed tomographic (HRCT) scan of the chest. RESULTS: There was a wide range of
      impairment of FEV(1) which was in the normal range (>/=80%) in 30%, mildly
      impaired (60-79%) in 18%, moderately impaired (40-59%) in 33%, and severely
      impaired (<40%) in 19% of patients. A reduced FEV(1)/VC ratio was present in all
      patients with an FEV(1) of <80% predicted but also in 41% of those with an FEV(1)
      of >/=80% predicted. Only 5% of patients had a substantial bronchodilator
      response suggesting a diagnosis of asthma. Emphysema was present in 51% of
      patients and confined to the upper lobes in most (73% of these patients). HRCT
      evidence of bronchiectasis was noted in 29% of patients and was predominantly
      tubular; most (81%) were current or ex-smokers. A solitary pulmonary nodule was
      seen on 9% of scans and unsuspected lung malignancy was diagnosed in two
      patients. CONCLUSIONS: This study confirms that COPD in primary care is a
      heterogeneous condition. Some patients do not fulfil the proposed diagnostic
      criteria with FEV(1) of >/=80% predicted but they may nevertheless have airflow
      obstruction. Bronchiectasis is common in this group of patients, as is
      unsuspected malignancy. These findings should be considered when developing
      recommendations for the investigation and management of COPD in the community.

PMID- 10899239
TI  - Capsaicin responsiveness and cough in asthma and chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Chronic cough is associated with an increased sensitivity to inhaled
      capsaicin in a number of conditions but there are no data for patients with more
      severe asthma or chronic obstructive pulmonary disease (COPD). Moreover, the
      relationships between the capsaicin response (expressed as the concentration of
      capsaicin provoking five coughs, C5), self-reported cough, and routine medication
      is not known. METHODS: The cough response to capsaicin in 53 subjects with
      asthma, 56 subjects with COPD, and 96 healthy individuals was recorded and
      compared with a number of subjective measures of self-reported cough, measures of
      airway obstruction, and prescribed medication. In asthmatic subjects the
      relationships between the cough response to capsaicin and mean daily peak flow
      variability and non-specific bronchial hyperresponsiveness to histamine were also
      examined. RESULTS: Subjects with asthma (median C5 = 62 mM) and COPD (median C5 =
      31 mM) were similarly sensitive to capsaicin and both were more reactive than
      normal subjects (median C5 >500 mM). Capsaicin sensitivity was related to
      symptomatic cough as measured by the diary card score in both asthma and COPD (r
      = -0.38 and r = -0.44, respectively), but only in asthma and not COPD when
      measured using a visual analogue score (r = -0.32 and r = -0.05, respectively).
      Capsaicin sensitivity was independent of the degree of airway obstruction and in
      asthmatics was not related to PEF variability or PC(20) for histamine. The
      response to capsaicin was not related to treatment with inhaled corticosteroids
      but was increased in those using anticholinergic agents in both conditions.
      CONCLUSIONS: These data suggest that an increased cough reflex, as measured by
      capsaicin responsiveness, is an important contributor to the presence of cough in
      asthma and COPD, rather than cough being simply secondary to excessive airway
      secretions. The lack of any relationship between capsaicin responsiveness and
      airflow limitation as measured by the FEV(1) suggests that the mechanisms
      producing cough are likely to be different from those causing airways
      obstruction, at least in patients with COPD.

PMID- 10899240
TI  - Systemic effects of formoterol and salmeterol: a dose-response comparison in
      healthy subjects.
AB  - BACKGROUND: The main adverse effects of inhaled long acting beta(2) agonists
      relate to their systemic activity. The systemic effects seen over eight hours
      after inhalation of three doses of salmeterol and formoterol were therefore
      compared in normal subjects. METHODS: A double blind, randomised, crossover study
      was carried out in 16 healthy subjects who inhaled formoterol 24, 48 and 96
      microg (via Turbuhaler((R))), salmeterol 100, 200 and 400 microg (via
      Diskhaler((R))), or placebo on separate days. Heart rate, systolic and diastolic
      blood pressure, and plasma potassium and glucose concentrations were measured for
      eight hours following each drug and mean values were used to plot the time course
      of change after each dose. Mean maximum (or minimum) absolute values were used to
      construct dose-response curves to calculate the relative dose potency of the two
      drugs. Lunch was taken after the four hour readings and, since this caused
      additional changes to the main outcome measures, data from the first four hours
      are also presented in a post hoc analysis. RESULTS: Both salmeterol and
      formoterol caused an early dose dependent increase in heart rate and glucose
      concentrations and a fall in diastolic blood pressure and plasma potassium
      concentration; formoterol also caused an early increase in systolic blood
      pressure. The cardiovascular effects occurred more rapidly than the metabolic
      effects and the response to formoterol was faster than that of salmeterol, apart
      from the glycaemic response. The effects of salmeterol were slightly more
      prolonged than those of formoterol, although some dose related effects were
      apparent at eight hours with both drugs. The relative dose potency for formoterol
      compared with salmeterol at four and eight hours for the different end points
      excluding systolic blood pressure ranged from 1.6 to 7.0 after adjusting for
      baseline values. Relative dose potencies (95% CI) for maximum heart rate and
      plasma potassium concentrations were 4.1 (3.0 to 5.6) and 5.8 (4.1 to 8.6) over
      four hours and 2.4 (1.2 to 3.8) and 3.0 (1.2 to 5.7) over eight hours.
      CONCLUSIONS: Formoterol and salmeterol cause dose related changes in heart rate,
      diastolic blood pressure, and plasma glucose and potassium concentrations.
      Formoterol has a more rapid onset for most end points whereas salmeterol has
      slightly more prolonged activity. Both drugs have a relatively modest therapeutic
      window. The relative dose potencies of the two drugs for the main end points were
      similar to the fourfold difference in recommended doses. Some differences in the
      pharmacological profile of the two drugs emerged and are as yet unexplained.

PMID- 10899241
TI  - Declining incidence of episodes of asthma: a study of trends in new episodes
      presenting to general practitioners in the period 1989-98.
AB  - BACKGROUND: A study was undertaken to determine trends in the incidence of new
      episodes of asthma presented to general practitioners participating in the Weekly
      Returns Service of the Royal College of General Practitioners, comprising 92
      practices with a registered population of approximately 680 000 persons well
      distributed throughout England and Wales. These practices monitor the morbidity
      presented at every consultation, distinguishing between new episodes of illness
      and ongoing consultations. METHODS: Age specific weekly rates of new episodes of
      asthma (and of acute bronchitis) presenting to the general practitioners over the
      years 1989-98 were examined in four week blocks and analysed by multiple
      regression, separating secular from seasonal trends. RESULTS: Quadratic trends in
      episodes of asthma were evident in each of the age groups with peaks in 1993/4.
      Corresponding analyses for acute bronchitis disclosed similar trends generally
      peaking in the winter of 1993/4. Mean weekly incidence data (all ages combined)
      decreased in all quarters since 1993. Regional analysis (North/Central/South)
      showed similar decreases. CONCLUSIONS: There has been a gradual decrease in the
      incidence of asthma episodes and of acute bronchitis presenting to general
      practitioners since 1993. The trend of an increase before 1993 followed by a
      decrease cannot be explained by changes in the patterns of health care usage or
      diagnostic preference of doctors.

PMID- 10899242
TI  - Comparison of the seasonal patterns of asthma identified in general practitioner
      episodes, hospital admissions, and deaths.
AB  - BACKGROUND: Seasonal variations in asthma are widely recognised. This study was
      undertaken to investigate the relative differences in seasonal patterns by age as
      they impact on episodes of care in general practice, hospital admissions, and
      deaths. METHODS: General practice episode data from the Weekly Returns Service of
      the Royal College of General Practitioners, hospital admissions for asthma in
      England, and deaths registered as due to asthma in England and Wales over the
      years 1990-7 were examined. Age specific weekly rates of new episodes of asthma
      presenting to general practitioners, numbers of hospital admissions and deaths
      were analysed by the multiplicative decomposition method to separate secular from
      seasonal trends. The seasonal indices thereby obtained were plotted as three week
      moving averages. RESULTS: In children aged 0-4 and 5-14 years general practice
      episodes and admissions to hospital were strikingly congruent in timing and in
      magnitude, except in September when particularly high rates of admission
      (absolute and relative to general practice episodes) occurred. In the 15-44 age
      group there were marked mid summer peaks of general practice episodes and deaths
      but admissions to hospital were at about the annual average; in September/October
      there were peaks of episodes and admissions whereas deaths peaked in November. In
      the 45-64 age group a peak in general practice episodes of asthma was evident in
      mid summer when admissions were about average and deaths were at a minimum; all
      three measures tended to increase gradually with the approach of winter. Finally,
      in those age over 65 years, general practice episodes of asthma, admissions to
      hospital, and deaths followed similar 'U' shaped patterns with substantial peaks
      in mid winter. CONCLUSIONS: The seasonal pattern of asthma evolves with age.
      There are important differences in the seasonal pattern of general practice
      episodes, admissions to hospital, and deaths. Individual seasonal histories are
      important for the management of asthma. The combined analysis of these three data
      sets provides a new perspective on the epidemiology of asthma.

PMID- 10899243
TI  - Epidemiology of pneumothorax in England.
AB  - BACKGROUND: Little is known of the epidemiology of pneumothorax. Routinely
      available data on pneumothorax in England are described. METHODS: Patients
      consulting in primary care with a diagnosis of pneumothorax in each year from
      1991 to 1995 inclusive were identified from the General Practice Research
      Database (GPRD). Emergency hospital admissions for pneumothorax were identified
      for the years 1991-4 from the Hospital Episode Statistics (HES) data. Mortality
      data for England & Wales were obtained for 1950-97. Analyses of pneumothorax
      rates by age and sex were performed for all data sources. Seasonal and
      geographical analyses were carried out for the HES data. RESULTS: The overall
      person consulting rate for pneumothorax (primary and secondary combined) in the
      GPRD was 24. 0/100 000 each year for men and 9.8/100 000 each year for women.
      Hospital admissions for pneumothorax as a primary diagnosis occurred at an
      overall incidence of 16.7/100 000 per year and 5.8/100 000 per year for men and
      women, respectively. Mortality rates were 1. 26/million per year for men and
      0.62/million per year for women. The age distribution in both men and women
      showed a biphasic distribution for both GP consultations and hospital admissions.
      Deaths showed a single peak with highest rates in the elderly. There was an urban
      rural trend observed for hospital admissions in the older age group (55+ years)
      with admission rates in the conurbations significantly higher than in the rural
      areas. Analysis for trends in mortality data for 1950-97 showed a striking
      increase in the death rate for pneumothorax in those aged 55+ years between 1960
      and 1990, with a steep decline in the 1990s. Mortality in the younger age group
      (15-34 years) remained low and constant. CONCLUSION: There is evidence of two
      epidemiologically distinct forms of spontaneous pneumothorax in England. The
      explanation for the rise and fall in mortality for secondary pneumothorax is
      obscure.

PMID- 10899244
TI  - Attitudes to fertility issues among adults with cystic fibrosis in Scotland. The
      Collaborative Group of Scottish Adult CF Centres.
AB  - BACKGROUND: With increasing life expectancy, issues of fertility and pregnancy
      are pertinent to patients with cystic fibrosis. For this reason, the four
      Scottish Cystic Fibrosis centres asked men and women with cystic fibrosis about
      their attitudes to fertility and to information given to them by health
      professionals. METHODS: A postal questionnaire was sent to 116 men and 79 women
      aged 16 years and over attending four Scottish Cystic Fibrosis clinics. RESULTS:
      There was a 70% response rate (82 men, 54 women). All but two men knew that they
      were likely to be infertile. 37% of respondents lived with a partner; 14 women
      (26%) and five men (6%) had children. For 85% of men and 72% of women having
      children was important now or would be in the next 10 years. 43% of men and 26%
      of women had never had any discussion on fertility issues with cystic fibrosis
      health professionals. 56% of men thought that first discussion with a health
      professional about infertility should be before the age of 16 years; 12%
      remembered having a first discussion at that age. Learning of their infertility
      was associated with strong negative emotions for most men. Women were more likely
      than men to have initiated first discussion (17 (32%) versus eight (10%);
      p<0.01). Twenty five men (31%) and 32 women (59%) were currently using
      contraception. Ten men (12%) and 15 women (28%) had discussed contraception at
      the Cystic Fibrosis clinic (p = 0.01). CONCLUSIONS: Parenting and fertility
      issues are important for men and women with cystic fibrosis but many patients do
      not find out what they want to know from discussion with health professionals.
      Patients want discussion to begin in early adolescence. Men in particular are
      likely to be reluctant to introduce these issues; health professionals should be
      aware of the need actively to initiate discussion.

PMID- 10899245
TI  - Distinct effects of Broncho-Vaxom (OM-85 BV) on gp130 binding cytokines.
AB  - BACKGROUND: Broncho-Vaxom (OM-85 BV) is known to support respiratory tract
      resistance to bacterial infections. In vivo and in vitro studies in animals and
      humans have shown that the action of the drug is based on the modulation of the
      host immune response, and it has been found to upregulate interferon gamma (IFN
      gamma) and interleukin (IL)-2, IL-6, and IL-8. These immunomodulatory effects of
      the compound may explain its stimulation on T helper cells and natural killer
      cells. Following earlier findings that OM-85 BV induces the synthesis of IL-6, a
      study was undertaken to investigate its possible effect on other gp130 binding
      cytokines including IL-11, IL-12, leukaemia inhibitory factor (LIF), oncostatin M
      (OSM), and ciliary neutrophil factor (CNTF). Its modulation of the corresponding
      receptors of the above mentioned cytokines and of the signal transducer gp130 in
      human pulmonary fibroblasts and peripheral blood lymphocytes was also studied.
      METHODS: Transcription of cytokines was assessed by Northern blot analysis.
      Secretion of cytokines was analysed using commercially available enzyme linked
      immunosorbent assay kits. Cytokine receptors and gp130 proteins were determined
      by Western blot analysis. RESULTS: OM-85 BV increased the expression of IL-11 in
      human lung fibroblasts, but not in lymphocytes, in a dose and time dependent
      manner by maximal fivefold within 20 hours. The compound inhibited serum induced
      IL-12 expression in peripheral blood lymphocytes but did not induce OSM, LIF, or
      CNTF at any concentration. In lung fibroblasts the expression of the IL-6
      receptor was enhanced fourfold at a concentration of 10 microg/ml OM-85 BV while
      that of the IL-11 receptor was not altered. In peripheral blood lymphocytes LIF
      receptor alpha expression was downregulated in the presence of 10 microg/ml OM-85
      BV. At a concentration of 10 microg/ml OM-85 BV enhanced gp130 gene transcription
      fivefold and increased gp130 protein accumulation in cell membranes by 2.5 times.
      CONCLUSION: In vitro OM-85 BV exerts immunomodulatory action via modulation of
      the signal transducer gp130 and gp130 binding cytokines. The increase of IL-6 and
      IL-11 may explain enhanced T and B cell activity, immunoglobulin synthesis, and
      IgM to IgG switch. Suppression of IL-12 and LIF receptor-alpha further
      contributes to organ protection. With regard to gp130 mediated signalling of the
      investigated cytokines, OM-85 BV modifies the host immune response towards an
      increased sensitisation of cells to gp130 binding proteins.

PMID- 10899246
TI  - A hereditary haemorrhagic telangiectasia family with pulmonary involvement is
      unlinked to the known HHT genes, endoglin and ALK-1.
AB  - BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) occur in over 25% of
      patients with the autosomal dominant disorder hereditary haemorrhagic
      telangiectasia (HHT). Mutations in two genes, endoglin and ALK-1, are known to
      cause HHT. Each encodes a protein expressed on vascular endothelial cells and
      involved in signalling by members of the transforming growth factor (TGF)-beta
      superfamily. To date, PAVMs have not been detected in ALK-1 families. There is
      evidence from a single HHT family without pulmonary involvement that a third HHT
      gene may exist. To establish the existence of a further HHT gene responsible for
      PAVMs, linkage analyses were performed on an expanded PAVM-HHT family in which
      HHT did not result from endoglin mutations. METHODS: Family members were assessed
      clinically to assign HHT disease status and were screened for PAVMs. DNA was
      extracted from blood obtained from 20 individuals of known disease status. Short
      tandem repeat polymorphic markers spanning the intervals containing the endoglin
      and ALK-1 genes were amplified by the polymerase chain reaction using (33)P
      labelled oligonucleotide primers, separated by denaturing polyacrylamide gel
      electrophoresis (PAGE), and the resultant autoradiographs were examined for
      allele sizes. Linkage analyses were performed using MLINK and GENEHUNTER.
      RESULTS: Twelve members spanning four generations were affected with HHT. Two had
      proven PAVMs, one with a classical appearance, the other exhibiting microscopic
      PAVMs exacerbated by pregnancy. Two point lod and multipoint lod scores
      significantly excluded linkage to endoglin and ALK-1 in this pedigree.
      CONCLUSIONS: This study confirms the existence of a third HHT locus that accounts
      for disease in some HHT patients with pulmonary involvement.

PMID- 10899247
TI  - Maternal age at menarche and atopy among offspring at the age of 31 years.
AB  - BACKGROUND: Influences of female hormones on the occurrence of allergic disorders
      have been suggested. Age at menarche may be a marker of endogenous oestrogen
      levels. Data from a Finnish birth cohort followed to adulthood were analysed to
      determine whether there is any association between maternal age at menarche and
      the occurrence of atopy among offspring. METHODS: The study was conducted in 5188
      subjects born in northern Finland for whom data collections were started during
      pregnancy and a follow up examination was completed at the age of 31 years. Atopy
      was determined by skin prick tests with cat, birch, grass, and mite extracts, and
      doctor diagnosed asthma was ascertained by questionnaire at follow up. Maternal
      age at menarche was obtained from perinatal data. Logistic regression models were
      used to adjust for maternal age, parity, smoking, season of birth, parental
      allergy, and measures of adiposity and socioeconomic status. RESULTS: The
      prevalence of atopy at the age of 31 years was lower in children whose mothers
      reached menarche at a later age, especially after age 15. Compared with children
      whose mothers started menarche at the age of 16 or over, the adjusted odds ratios
      of being atopic for children whose mothers started menarche younger than or at
      12, 13, 14 and 15 years were 1.43 (95% CI 1.12 to 1.83), 1.29 (95% CI 1.03 to
      1.60), 1. 15 (95% CI 0.93 to 1.42), and 1.19 (95% CI 0.95 to 1.48), respectively.
      Among girls, the offspring's own age at menarche was not significantly associated
      with atopy. CONCLUSION: Our results encourage further evaluation of the potential
      effect of maternal age at menarche on the later development of atopy and possible
      biological mechanisms.

PMID- 10899248
TI  - A paired comparison of tuberculin skin test results in health care workers using
      5 TU and 10 TU tuberculin.
AB  - BACKGROUND: Historically, 10 TU has been employed in Australia and the United
      Kingdom to perform the tuberculin skin test (TST). However, this makes it
      difficult to compare the rates of TST positivity with other countries such as the
      USA who use 5 TU. To assess the impact of the dose of tuberculin on the TST a
      comparison was made of TST responses in health care workers given a TST with both
      5 and 10 TU. METHODS: Two TSTs were performed simultaneously in each health care
      worker using 5 and 10 TU. Each dose was randomly assigned in a blinded manner to
      the right or left forearm and read at 48-72 hours by a single nurse who was
      blinded to the assignment of the 5 and 10 TU doses. RESULTS: A total of 128
      health care workers were enrolled, 119 (93%) of whom had a past history of BCG
      vaccination. The overall mean difference in paired reaction sizes for the two
      doses was 1.5 mm with 95% limits of agreement of -3.6 to 6.5 mm. CONCLUSION: A
      slightly larger TST reading was seen with 10 TU than with 5 TU. The mean
      difference of 1.5 mm between the two doses should be considered when comparing
      rates of TST positivity between countries who use different doses of tuberculin
      to perform the tuberculin skin test.

PMID- 10899249
TI  - Correlation of CD4:CD8 ratio and tumour necrosis factor (TNF)alpha levels in
      induced sputum with bronchoalveolar lavage fluid in pulmonary sarcoidosis.
AB  - BACKGROUND: An increased CD4:CD8 lymphocyte ratio and raised cytokine levels in
      bronchoalveolar lavage (BAL) fluid are characteristic of pulmonary sarcoidosis.
      Sputum induction has been used as a non-invasive tool for investigating the
      airways and may be useful in investigating inflammation in patients with
      sarcoidosis in whom endobronchial, peribronchial, and parenchymal inflammation is
      present. This study aimed to correlate the total and differential cell counts,
      CD4:CD8 ratio, and tumour necrosis factor (TNF)alpha levels between induced
      sputum and BAL fluid in patients with pulmonary sarcoidosis. METHODS: Fourteen
      patients with newly diagnosed biopsy proven sarcoidosis and six healthy controls
      were investigated. Sputum induction and BAL was carried out at the initial visit
      and repeated following six months of treatment with oral prednisone. RESULTS:
      There was no correlation of differential cell counts between induced sputum and
      BAL fluid. The CD4:CD8 ratio in induced sputum correlated strongly with that in
      BAL fluid (5.5 (0. 4:1) versus 4.4 (0.2:1); r = 0.8, p<0.001) and the fall in the
      ratio following six months of treatment in sputum paralleled that in BAL fluid
      (3.4 (0.2:1) versus 2.4 (0.2:1)). The TNF alpha levels in sputum also correlated
      with levels in the BAL fluid (11.9 (1.5) pg/ml versus 17.6 (2.7) pg/ml; r = 0.8,
      p<0.001). The fall in sputum TNF alpha levels following six months of treatment
      paralleled the fall in BAL fluid levels (6.7 (0.9) pg/ml versus 11.6 (1.3)
      pg/ml). CONCLUSIONS: The CD4:CD8 ratio and TNF alpha levels in induced sputum
      correlated with those in BAL fluid and paralleled changes with treatment. Induced
      sputum may therefore be a non-invasive surrogate for certain parameters in BAL
      fluid in patients with sarcoidosis.

PMID- 10899250
TI  - Prevention of adult asthma by early intervention during childhood: potential
      value of new generation immunomodulatory drugs.

PMID- 10899252
TI  - Non-tuberculous mycobacterial lung infection complicated by chronic necrotising
      pulmonary aspergillosis.
AB  - We report four cases of pulmonary mycobacterial disease (three due to
      Mycobacterium malmoense and one to Myco- bacterium avium intracellulare)
      complicated by the development of chronic necrotising pulmonary aspergillosis.
      Difficulties with treatment and the potential benefits of steroids are discussed.

PMID- 10899253
TI  - Induced sputum examination: diagnosis of pulmonary involvement in Fabry's
      disease.
AB  - Fabry's disease is a rare inherited metabolic disorder caused by a deficiency in
      the enzyme alpha-galactosidase A. It can affect almost every organ, including the
      lungs. Confirmation of lung involvement has depended on invasive bronchial biopsy
      specimens or brushings to confirm the presence of typical lamellar inclusion
      bodies within bronchial epithelial cells. We report a patient with known Fabry's
      disease in whom these inclusion bodies were identified by examination of induced
      sputum.

PMID- 10899254
TI  - Role of photodynamic therapy in the management of advanced esophageal cancer.
AB  - Esophageal cancer usually presents at an advanced stage with dysphagia, and
      palliative therapy often is appropriate. Expandable metal stents are used for
      palliation because of their ease of insertion, but long-term complications remain
      common. Photodynamic therapy has been shown to be an effective ablative treatment
      for obstructing esophageal cancer, overall easier to use, and longer lasting than
      Nd:YAG laser ablation. Photodynamic therapy may be particularly useful in areas
      where stents may be problematic, such as in the upper esophagus, at the
      esophagogastric junction (where adenocarcinomas are increasing in frequency), and
      following radiation and chemotherapy.

PMID- 10899255
TI  - Photodynamic therapy of Barrett's esophagus.
AB  - Photodynamic therapy seems to be able to control high-grade dysplasia within
      Barrett's esophagus about 80% of the time. Long-term results are not available,
      but the treatment is promising. Given the success with surgical intervention,
      however, use of photodynamic therapy should be reserved for nonsurgical
      candidates at the current time. The complications that occur with photodynamic
      therapy are not trivial and must be weighed against the potential benefits.

PMID- 10899251
TI  - Respiratory muscle function and free radicals: from cell to COPD.

PMID- 10899256
TI  - Barrett's esophagus: treatment with 5-aminolevulinic acid photodynamic therapy.
AB  - Barrett's esophagus has been identified as the premalignant precursor of
      esophageal adenocarcinoma. The eradication of metaplastic or dysplastic columnar
      lined (Barrett's) esophagus may prevent progression to esophageal adenocarcinoma.
      5-Aminolevulinic acid photodynamic therapy is a simple method for the mucosal
      ablation of the abnormal segment. Areas of metaplastic epithelium may remain
      buried after treatment and continued surveillance is necessary. Repeated
      treatments often are necessary but are very well tolerated with few
      complications.

PMID- 10899257
TI  - Photodynamic therapy of gastric cancer.
AB  - Photodynamic therapy is a fascinating concept that will continue to occupy many
      research groups around the world in coming years. Although a widespread clinical
      application for the method has not yet emerged, there are good prospects that
      photodynamic therapy will establish itself at major gastroenterologic centers as
      an endoscopic procedure with few or no side effects in the treatment of Barrett's
      esophagus (sever dysplasia and early carcinoma) and, in selected cases, for the
      treatment of early gastric carcinoma.

PMID- 10899258
TI  - Photodynamic therapy of cholangiocarcinoma cancer.
AB  - Prognosis of nonresectable cholangiocarcinoma is not good, and in Bismuth type
      III and IV tumors relief of jaundice is seldom achieved, despite successful
      endoprosthesis insertion. Additional photodynamic therapy seems to be a promising
      new approach to these tumors. First pilot studies show relief of jaundice, mainly
      because of opening of the intrahepatic ducts and improvements in quality of life
      indices. Survival time seems to be long; however, randomized studies are
      necessary to confirm these results.

PMID- 10899259
TI  - Complications of photodynamic therapy in gastrointestinal disease.
AB  - The primary complications of photodynamic therapy of the esophagus include
      cutaneous photosensitivity and esophageal strictures. Atrial fibrillation and
      pleural effusion have been reported but appear to be rare or not clinically
      significant. Cutaneous photosensitivity can be minimized if the adequate
      precautions are taken to protect patients from sunlight exposure. Stricture
      formation may be decreased by proper dosimetry and avoiding multiple overlapping
      light applications.

PMID- 10899260
TI  - 5-Aminolevulinic acid-induced protoporphyrin IX for the detection of
      gastrointestinal dysplasia.
AB  - The detection of gastrointestinal dysplasia is an unresolved problem.
      Fluorescence detection of these premalignancies after exogenous application of 5
      aminolevulinic acid, which is converted to protoporphyrin IX and accumulates
      selectively in tumors, is an interesting approach. Illumination with light of
      appropriate wavelength allows the discrimination and detection of
      gastrointestinal neoplasia either by spectroscopy or fluorescence endoscopy
      because of a typical red fluorescence of protoporphyrin IX. Surveillance of
      patients with Barrett's esophagus and ulcerative colitis might benefit from this
      new technique.

PMID- 10899261
TI  - Light sources and delivery devices for photodynamic therapy in the
      gastrointestinal tract.
AB  - This article provides discussion on different light sources and light delivery
      devices used for photodynamic therapy of a variety of gastrointestinal
      malignancies. Different laser and nonlaser sources are discussed with emphasis on
      most commonly used clinical units. The discussion of light delivery devices is
      divided into several sections, each reviewing the evolution of fiberoptic
      delivery devices for different gastrointestinal malignancy. A discussion is
      provided on power meters and wavelength calibration devices used to assure proper
      light dosimetry. Finally, a short discussion is provided on a technique used to
      improve endoscopic monitoring of photodynamic therapy procedure during the
      treatment.

PMID- 10899262
TI  - The biology of photodynamic therapy in the gastrointestinal tract.
AB  - This article reviews current knowledge on the biology of photodynamic therapy on
      normal and diseased tissues in the gastrointestinal tract. There is little effect
      on connective tissue, so the mechanical integrity of the luminal gut is well
      preserved, even with full thickness damage. This makes photodynamic therapy
      suitable for treating small tumors, but strictures may occur after
      circumferential treatment of conditions like Barrett's esophagus unless a muscle
      sparing photosensitizing agent is used. Animal studies show that the pancreas and
      surrounding tissues can tolerate photodynamic therapy, justifying pilot clinical
      trials on percutaneous, interstitial photodynamic therapy for localized,
      inoperable pancreatic cancers.

PMID- 10899263
TI  - Hypercapnic respiratory failure during weaning: neuromuscular capacity versus
      muscle loads.
AB  - Patients who fail a weaning trial develop hypercapnia as a result of alveolar
      hypoventilation, which, in turn, is caused by an imbalance between the
      respiratory muscle load and capacity. In some patients, especially those with
      obstructive lung diseases, respiratory muscle performance is impaired as a result
      of dynamic hyperinflation and paradoxical motion of the rib cage and abdomen.
      Worsening of pulmonary mechanics causes further embarrassment of the respiratory
      muscles and can lead to marked alterations of oxygen use by the peripheral
      tissues. The development of rapid shallow breathing together with worsening of
      pulmonary mechanics results in inefficient clearance of COcf152cf1 during a
      failed weaning attempt.

PMID- 10899264
TI  - Ventilators and weaning modes.
AB  - Although new ventilator modes have become available to facilitate weaning, there
      is little evidence that these have improved weaning outcomes. Knowledge based
      computer weaning systems have also been described, but these are in their
      infancy, and their role is unclear. Prospective, randomized clinical studies are
      required to examine whether such modalities are superior to existing approaches.

PMID- 10899266
TI  - Summarizing the logistics of liberation from mechanical ventilation.
AB  - A goal of critical care clinicians should be to liberate patients from
      ventilators on the first possible day to avoid the multitude of complications
      associated with prolonged mechanical ventilation. The past decade has been marked
      by a deluge of scientific studies that have illuminated methods to expedite
      successful liberation from mechanical ventilation. This article summarizes the
      principle themes for this issue of Respiratory Care Clinics of North America and
      distills the available data to two simple weaning algorithms.

PMID- 10899265
TI  - Approach to patients with long-term weaning failure.
AB  - Efforts to treat reversible disease processes that contribute to ventilator
      dependency in the intensive care unit (ICU) fail in up to 20% of patients,
      resulting in prolonged mechanical ventilation (PMV). Resolution of the insults
      that necessitated ICU admission and mechanical ventilation may be incomplete, and
      the economic pressure to transfer patients is ever increasing. The choice of post
      ICU disposition depends on the patient's clinical condition, the resources of the
      transfer destination, and whether weaning attempts will continue. This article
      reviews data from a decade of weaning beyond the ICU, including outcomes of more
      than 2700 patients with PMV afforded continued attempts at liberation in long
      term acute care facilities and other post-ICU weaning venues. Assessment and
      treatment, weaning strategies, and complications of patients with PMV are
      described.

PMID- 10899267
TI  - Sexual Activity and Cardiac Risk: The Princeton Conference. New Jersey, USA, June
      1999.

PMID- 10899268
TI  - Sexual activity and cardiac risk: the Princeton Conference. Introductory
      comments.

PMID- 10899269
TI  - Sexual activity and cardiac risk: overview of epidemiologic research methods.
AB  - The goal of clinical research is to differentiate among the different possible
      types of associations between the factors under study: no association,
      artifactual association, indirect association, and causal association. This
      article is intended as a brief overview of the research methods used in clinical
      research to differentiate these types of associations. It begins with an overview
      of the scientific method and the types of errors that can be made (i.e., random
      error, confounding, and bias). It then discusses the criteria supporting the
      causal nature of an association (i.e., how can one tell when an association is
      causal?). The criteria reviewed are (1) coherence with existing information; (2)
      time sequence; (3) specificity; (4) consistency; and (5) strength. Included
      within the last are quantitative strength, dose-response relation, and study
      design. Finally, the article provides a very brief outline of the available
      research designs, i.e. , experimental studies, cohort studies, case-control
      studies, analyses of secular trends, case series, and case reports, and the
      advantages and disadvantages associated with each.

PMID- 10899270
TI  - Sex and myocardial infarction: an epidemiologic perspective.
AB  - The relation between sexual activity and acute myocardial infarction (MI) risk is
      one of great interest to people at risk for MI and their physicians. However,
      understanding this relation requires an appreciation of the complex interplay
      among relative, attributable, and absolute risk. Because there is an underlying
      risk of MI in the population, the risk of MI after sexual activity must be
      compared with this underlying baseline risk. The estimated relative risk of MI
      after sexual activity is approximately 2.5 during the 2-hour period after sex,
      indicating a 2.5-fold increase in risk over baseline. However, because the
      baseline risk during any 2-hour period is very low, the absolute increase in risk
      (the risk from sexual activity minus the baseline risk), is extremely small
      (e.g., 0.01% over a year for low-risk individuals engaging in weekly sexual
      activity and 0.1% for higher-risk individuals). In addition, the attributable
      risk (the percentage of MIs due to sexual activity) is <1%. Thus, any
      individual's risk of MI during sexual activity is low. Nonetheless, factors that
      may decrease the risk of MI after sexual activity are important to explore, and
      include regular exercise and perhaps medication use, such as aspirin and beta
      blockers. Although there may be a long-term cardiovascular and mortality benefit
      to regular sexual activity, current data supporting this theory are limited. This
      article describes the relation between sexual activity and acute MI with respect
      to the complex interplay among relative, attributable, and absolute risk.
      Limitations of studies examining the potential long-term benefits of regular
      sexual activity are also discussed.

PMID- 10899271
TI  - Triggering of cardiac events by sexual activity: findings from a case-crossover
      analysis.
AB  - Although anecdotal reports have suggested that sexual activity increases the risk
      of acute myocardial infarction (MI), controlled studies to evaluate the magnitude
      of this risk have only recently been conducted. Using an epidemiologic technique
      called the case-crossover method, the Myocardial Infarction Onset Study (MIOS)
      has provided quantitative data on sexual activity as a trigger of MI onset.
      Sexual activity was found to double the relative risk of acute MI in healthy
      individuals and patients with a prior history of angina or MI. However, the
      absolute risk of sexually triggered MI remains extremely low, because the
      baseline risk of MI is low for most individuals and the increased risk due to
      sexual activity is transient. Regular exercise also was found to reduce the risk
      of MI by sexual activity. Given that >12 million people in the United States have
      coronary artery disease, these findings should be more widely disseminated to
      reassure patients that, in most cases, sexual activity carries little risk of
      causing a cardiac event. In the future, advances in research on the triggering of
      MI are likely to yield new approaches to the prevention of cardiovascular events
      through prospective identification of the vulnerable plaques that lead to
      coronary thrombosis, and prophylactic measures to sever the link between triggers
      and their potentially disastrous consequences.

PMID- 10899272
TI  - Central control of the cardiovascular and erection systems: possible mechanisms
      and interactions.
AB  - Sexual activity is accompanied by vascular changes mediated by parasympathetic
      and sympathetic outflow to the peripheral organs. The brain stem and spinal cord
      contain the neurons that innervate the cardiovascular system and the penis. Heart
      rate and blood pressure increase, suggesting a decrease of the cranial
      parasympathetic outflow and an increase of the activity of sympathetic efferent
      pathways. In contrast, penile erection occurs in response to increased activity
      of the sacral parasympathetic innervation and a decreased activity of sympathetic
      pathways. A modulation of the balance between sympathetic and parasympathetic
      activities may result from an adaptation of an intraspinal network that (1) would
      be the recipient of peripheral and supraspinal information; and (2) would
      coordinate the activity of the different efferent pathways. A variety of nuclei
      in the medulla, pons, and hypothalamus contain premotor neurons that exert an
      influence on brain stem and spinal autonomic motoneurons. These descending
      pathways release amines (noradrenaline, adrenaline, serotonin, dopamine) and
      peptides. A fine tuning of brain stem and spinal activity is made possible by the
      great variety of receptor subtypes through which these neuromediators act. More
      recently, the role of nitric oxide, synthesized and released by different cell
      populations, has been evaluated in the brain and spinal control of the
      cardiovascular system and penile erection. Depending on its central neural
      target, nitric oxide may either activate or inhibit the cardiovascular system. In
      contrast, its role on the central control of penile erection is only excitatory.

PMID- 10899273
TI  - Penile erection and cardiac risk: pathophysiologic and pharmacologic mechanisms.
AB  - Erection is initiated through the parasympathetic nervous system, activation of
      which overrides the sympathetic tone that maintains the penis in a nonerectile
      (flaccid) state. This state is maintained mainly through the release of
      norepinephrine from penile adrenergic nerves. Norepinephrine contracts the
      vasculature and cavernosal smooth muscle. Arousal/erection is associated with a
      decrease of norepinephrine release in the penis, with a release of nitric oxide,
      and with a reduction in penile smooth muscle tone. It is also associated with
      minor cardiovascular changes. Heart rate increases by 4-8 beats per minute, on
      average, and the rate-pressure product and oxygen consumption increase by
      approximately 25%. There may be no changes in systemic venous norepinephrine
      concentrations; systemic venous epinephrine concentrations increase by about 60%.
      Drugs initiating or enhancing erection act by inhibiting norepinephrine-induced
      contraction (e.g., phentolamine) or by enhancing or directly inducing relaxation
      of the corpora cavernosa and the penile vasculature (e.g., sildenafil). Despite
      potentially negative hemodynamic actions when given parenterally, oral
      phentolamine-in doses required for enhancing erection-appears to produce few
      cardiovascular adverse effects. The hemodynamic effects of sildenafil are small,
      even in patients with coronary artery disease. However, the effects of the drug
      on human myocardium have not been conclusively established, and should be further
      investigated. As judged by available information, the cardiac risk associated
      with erection, with or without enhancement of drugs currently used for treatment
      of erectile dysfunction, is low.

PMID- 10899274
TI  - Cardiovascular response to sexual activity.
AB  - The cardiovascular response to coitus and the risk of an acute cardiac event
      related to sexual activity is of clinical importance, especially now that
      effective pharmacologic treatment of male erectile dysfunction permits older men
      to resume active sex lives. Early studies by Masters and Johnson of young
      subjects engaging in coitus in laboratory settings reported that heart rates and
      systolic blood pressures were at near maximum exercise levels. Subsequent data
      from studies by Hellerstein and Friedman and by Stein in men with coronary artery
      disease, using ambulatory electrocardiographic recordings during coitus at home,
      demonstrated significantly lower heart rate and blood pressure responses to
      coitus. The associated myocardial oxygen demand of coitus in these men was found
      to in the range of moderate activities, often achieved or exceeded during their
      workday. The cardiovascular risk of coitus was addressed in the recent ONSET
      study in which myocardial infarction (MI) patients were interviewed shortly after
      their MI about potential triggering activities or events. Coitus was noted to
      represent a very low absolute risk of being a trigger for MI, but had an
      increased relative risk of 2.5 for the subjects in their study. Sexual
      intercourse will, in most men, represent only a moderate "stress" on the heart in
      terms of the responses that impact on myocardial oxygen requirement (heart rates,
      and systolic blood pressure). In patients with coronary artery atherosclerosis,
      coitus, compared with vigorous physical activity and intense emotional responses,
      represents a small risk of triggering an acute MI.

PMID- 10899275
TI  - Sympathetic nervous system activity and female sexual arousal.
AB  - The results of a series of human and animal studies that were conducted in an
      effort to better understand autonomic nervous system influences on female sexual
      arousal are presented. The effects of sympathetic nervous system (SNS) activation
      on self-report and vaginal photoplethysmographic measures of sexual arousal were
      examined in 4 studies using intense acute exercise, and in 1 study using
      ephedrine, to activate the SNS. The effects of SNS inhibition on sexual responses
      in the female rat were examined in 3 studies using clonidine, an alpha(2)
      adrenergic agonist; guanethidine, a postganglionic noradrenergic blocker; and
      naphazoline, an alpha(2)-adrenoreceptor agonist, to inhibit sympathetic outflow.
      In humans, the effects of SNS inhibition on subjective and physiologic sexual
      arousal were also examined using clonidine to suppress SNS activity. Together,
      the findings from these studies suggest that SNS activation may facilitate, and
      SNS inhibition inhibit, the early stages of sexual arousal in sexually functional
      women and in women with low sexual desire.

PMID- 10899276
TI  - Sexual intercourse and stable angina pectoris.
AB  - Stable angina pectoris is a common condition associated with chest pain
      predictable for a given level of exercise. Sexual intercourse does not lead to
      exaggerated heart rate or blood pressure responses and is interpreted by the
      heart as one of many forms of activity that may take place in a 24-hour period.
      Stable angina patients optimally treated are not at significantly increased
      cardiovascular risk during sexual intercourse. Erectile dysfunction (ED)
      increases with age and shares similar cardiovascular risk factors with stable
      angina. Sildenafil citrate can be safely prescribed for stable patients with ED
      providing they are not taking oral, topical, or sublingual nitrates. Sexual
      relationships should not be constrained by the diagnosis of angina pectoris
      provided appropriate medical advice is given on risk status. Family physicians
      and specialists are able to provide this advice based on their knowledge of the
      patient and the social circumstances. Impersonal advice is potentially dangerous
      and should be vigorously discouraged.

PMID- 10899277
TI  - Sexual activity and cardiac risk: is depression a contributing factor?
AB  - There is a well-documented association between depression, ischemic heart
      disease, and cardiovascular mortality. This association has a number of
      dimensions including: (1) depressed patients have a higher than expected rate of
      sudden cardiovascular death; (2) over the course of a lifetime, patients with
      depression develop symptomatic and fatal ischemic heart disease at a higher rate
      compared with a nondepressed group; and (3) depression after myocardial
      infarction (MI) is associated with increased cardiac mortality. Depression is
      also associated with sexual dysfunction, particularly erectile dysfunction. If
      depression is the primary illness, then erectile dysfunction can be considered a
      symptom of the depressive illness. However, if the erectile dysfunction is
      primary, men may develop a depressive syndrome in reaction to the loss of sexual
      function. Regardless of whether erectile dysfunction is a symptom of depression
      or depression is a consequence of erectile dysfunction, these conditions are
      frequently comorbid. Thus, the patient with ischemic heart disease who is
      depressed is more likely to have erectile difficulties. An attempt by this
      patient to engage in sexual activity is therefore more likely to be unsuccessful
      and, given the increase in cardiac mortality associated with depression, it may
      result in a serious cardiac event.

PMID- 10899278
TI  - The mutually reinforcing triad of depressive symptoms, cardiovascular disease,
      and erectile dysfunction.
AB  - The conditions of depression, erectile dysfunction (ED), and cardiovascular
      disease may seem at a superficial level as independent medical problems managed
      by 3 separate and unrelated healthcare disciplines. Various studies, however,
      have revealed significant associations between depression and cardiovascular
      disease, ED and cardiovascular disease, and depression and ED. The purpose of
      this research was to identify whether the 3 medical conditions share mutually
      reinforcing associations and predictors. Population-based epidemiologic studies
      were utilized where possible. Variables including age, heart disease,
      hypertension, sedentary behavior, related medications, cigarette smoking, and
      abnormal lipids have been found to be highly associated with depressive symptoms,
      cardiovascular disease, and ED. It was concluded that all 3 medical conditions
      share many of the same risk factors and etiologic associations and may be best
      modeled in a 3-way holistic, mutually reinforcing relation. Of particular
      relevance, patients with sexual dysfunction have a likely comorbidity of
      cardiovascular disease and depression, as well as the potential increased risk
      for cardiac morbidity and mortality.

PMID- 10899279
TI  - Cardiac disease, anxiety, and sexual functioning.
AB  - Despite the growing amount of reseach on cardiac disease and sexual dysfunction,
      few empirical studies have been published on the overlap of these 2 areas. In
      particular, previous research has noted that the overall attainment of social and
      occupational adjustment for patients with cardiac disease remains a challenge.
      Emotional distress of sufficient intensity to receive a psychiatric diagnosis has
      been estimated to be as high as 37-58% in patients after myocardial infarction
      (MI). In fact, numerous studies have concluded that failure to adjust socially or
      to return to normal activity levels is more strongly related to psychological
      distress than to the extent of the organic disease itself. These factors, either
      pre-existing or after onset of psychological morbidity, are highly likely to
      influence sexual adjustment of the cardiac patient. This article reviews the role
      of anxiety as a risk factor for the development of cardiac disease, as a comorbid
      condition, and the role anxiety may play in the development of sexual
      difficulties. The complicated association between psychological distress,
      previous sexual adjustment, organic factors, and existing family supports should
      be considered in cardiac rehabilitation.

PMID- 10899280
TI  - Evaluating the cardiovascular tolerance for sex.
AB  - The cardiovascular tolerance for sex has largely been equated with physical
      activity, yet sexual arousal plays a major role. Exercise testing is useful,
      primarily for evaluating functional capacity, which reflects the extent of
      physical conditioning and the limitation imposed by symptoms of angina, dyspnea,
      and fatigue. Exercise testing, which is useful for evaluating functional capacity
      in sedentary patients, is generally unnecessary in physically active patients.
      Exercise testing, with or without radionuclide imaging, is of limited value in
      assessing the risk of future cardiovascular events-a limitation shared by all
      diagnostic tests, including coronary angiography. The absolute risks of coition
      induced myocardial infarction (MI) or death are extremely low-on the order of 2
      chances per million per hour in healthy middle-aged individuals or 20 chances per
      million per hour in "high-risk" patients with ischemic heart disease. This is
      equivalent to an annual risk of 1. 01% and 1.2%, respectively. Sex is a
      comparatively weak precipitant of acute coronary events, accounting for only 0.5
      1.0% of all such events. The cardiovascular tolerance for sex in an individual
      can be characterized by the "functional reserve," that is, the extent to which
      the cardiovascular response to sex-measured by the heart rate, blood pressure,
      and oxygen consumption-encroaches on the peak response to exercise.
      Cardiovascular symptoms during sex rarely occur in patients who do not experience
      similar symptoms during exercise testing at a level equivalent to 6 METS.

PMID- 10899281
TI  - Cardiovascular risk and sildenafil.
AB  - Sildenafil citrate is the first oral agent approved for the treatment of erectile
      dysfunction (ED); other oral agents are in the process of development. Because
      the mechanism of action of many of these agents involves vasodilation, there is a
      potential for interaction with the cardiovascular system. Sildenafil inhibits
      phosphodiesterase-5 (PDE-5) which is found in the corpus cavernosum and in the
      systemic vasculature. Sildenafil causes a mild decrease in systemic arterial
      pressure ( approximately -8/-5.5 mm Hg); it causes a synergistic and often major
      decrease in systemic arterial pressure in the presence of organic nitrates
      (nitric oxide donors). Sildenafil is therefore contraindicated in patients taking
      organic nitrates. A review was made of clinical trials in populations of men with
      (1) erectile dysfunction; (2) chronic stable ischemic heart disease and erectile
      dysfunction; and (3) hypertension and erectile dysfunction. This review showed
      that sildenafil was effective and not associated with an increase in serious
      cardiovascular adverse events, myocardial infarction (MI), or death compared with
      placebo. Although there have been spontaneous reports of death among men using
      sildenafil, there are limitations to spontaneous-event reporting. In addition.
      the numbers of such reports are well below the expected numbers of deaths when
      considering the number of men who have received prescriptions for sildenafil and
      their age and cardiovascular risk factor profile. Because there is a small but
      finite risk of having a cardiac event with sexual activity, physicians should
      discuss with their cardiac patients the risks of sexual activity before
      prescribing any treatment for ED. In addition, they should evaluate their
      patients' cardiac status when considering the safety of administering any ED
      treatment that may have systemic vasodilatory properties and can potentially
      lower blood pressure. In some cases, exercise treadmill testing may be warranted
      to determine whether ED patients with coronary artery disease can achieve the
      physiologic workload (4-6 metabolic equivalents) associated with sexual
      intercourse.

PMID- 10899282
TI  - Management of sexual dysfunction in patients with cardiovascular disease:
      recommendations of the Princeton Consensus Panel.
AB  - Sexual dysfunction is highly prevalent in both sexes and adversely affects
      patients' quality of life and well being. Given the frequent association between
      sexual dysfunction and cardiovascular disease, in addition to the potential
      cardiac risk of sexual activity itself, a consensus panel was convened to develop
      recommendations for clinical management of sexual dysfunction in patients with
      cardiovascular disease. Based upon a review of the research and presentations by
      invited experts, a classification system was developed for stratification of
      patients into high, low, and intermediate categories of cardiac risk. The large
      majority of patients are in the low-risk category, which includes patients with
      (1) controlled hypertension; (2) mild, stable angina; (3) successful coronary
      revascularization; (4) a history of uncomplicated myocardial infarction (MI); (5)
      mild valvular disease; and (6) no symptoms and <3 cardiovascular risk factors.
      These patients can be safely encouraged to initiate or resume sexual activity or
      to receive treatment for sexual dysfunction. An important exception is the use of
      sildenafil in patients taking nitrates in any form. Patients in the intermediate
      risk category include those with (1) moderate angina; (2) a recent MI (<6 weeks);
      (3) left ventricular dysfunction and/or class II congestive heart failure; (4)
      nonsustained low-risk arrhythmias; and (5) >/=3 risk factors for coronary artery
      disease. These patients should receive further cardiologic evaluation before
      restratification into the low- or high-risk category. Finally, patients in the
      high-risk category include those with (1) unstable or refractory angina; (2)
      uncontrolled hypertension; (3) congestive heart failure (class III or IV); (4)
      very recent MI (<2 weeks); (5) high-risk arrhythmias; (6) obstructive
      cardiomyopathies; and (7) moderate-to-severe valvular disease. These patients
      should be stabilized by specific treatment for their cardiac condition before
      resuming sexual activity or being treated for sexual dysfunction. A simple
      algorithm is provided for guiding physicians in the management of sexual
      dysfunction in patients with varying degrees of cardiac risk.

PMID- 10899283
TI  - Adaptative effects of loss of vision on upright undisturbed stance.
AB  - In order to evaluate the long term effect of blindness on an undisturbed postural
      task, seven blind individuals (BLI) were compared to twelve healthy individuals
      (REF) who were required to close their eyes. To this aim, centre of pressure (CP)
      trajectories were recorded through a force platform on which the subjects
      remained upright. Through a low-pass filter, the vertical projection of the
      centre of gravity (CG(v)) and consequently the difference CP-CG(v) were
      estimated. The former represents the controlled variable whilst the latter is
      assumed to express the resultant joint stiffness. A first analysis consisted in
      studying the frequency distribution of these motions. Increased mean amplitudes
      in both elementary motions and no difference between frequency distributions were
      observed for the BLI when compared to the REF group. These trajectories were then
      modelled as a fractional Brownian motion process in order to gain insight about
      the nature of the control mechanisms called into play and their spatio-temporal
      organisation. Moreover, the main characteristic observed in the BLI group is a
      decreased in CP-CG(v) motions, which, according to Winter's model, may be related
      to joint stiffness. In addition, reduced spatial transition point co-ordinates
      and more deterministic control mechanisms aimed at returning the estimated CG to
      an equilibrium point during the longest Deltat were observed. This phenomenon is
      more pronounced in the antero-posterior direction and also allows the blind
      subject to significantly diminish their CG sways. Finally, these features are
      discussed in relation to other similarly analysed investigations.

PMID- 10899284
TI  - Riluzole increases high-affinity glutamate uptake in rat spinal cord
      synaptosomes.
AB  - The purpose of this study was to examine the effect of the anti-convulsant agent,
      riluzole, on high-affinity glutamate uptake as measured in rat spinal cord
      synaptosomes. The rate of glutamate uptake was significantly increased in the
      presence of 0.1 microM and 1.0 microM riluzole, but not at the higher
      concentrations examined. Kinetics analysis demonstrated that riluzole (0.1
      microM) decreased the apparent K(m) by 21% and increased the V(max) by 31%.
      Glutamate uptake also was significantly increased in spinal cord synaptosomes
      obtained from rats treated with 8 mg/kg (i.p.) of riluzole and sacrificed 4 h
      later. The increase in glutamate uptake in vitro was not affected by pretreatment
      either with H7, an inhibitor of PKA and PKC, or with the PKC activating phorbol
      ester, 12-O-tetradecanoylphorbol 13-acetate. Previous studies have shown that
      some of the actions of riluzole are mediated by G proteins sensitive to pertussis
      toxin. Surprisingly, treatment of synaptosomes with pertussis toxin alone
      increased the rate of glutamate uptake, while having no effect on uptake in the
      presence of riluzole. However, pretreatment with cholera toxin was found to
      completely block the effects of riluzole on glutamate uptake. These results
      reveal an additional mechanism by which riluzole can affect glutamatergic
      neurotransmission, and provides further support that riluzole may prove
      beneficial in the treatment of traumatic central nervous system injuries
      involving the excitotoxic actions of glutamate.

PMID- 10899285
TI  - Inflammation-induced changes in primary afferent-evoked release of substance P
      within trigeminal ganglia in vivo.
AB  - Substance P (SP) is synthesized in a subset of nociceptive sensory neurons and is
      released from their peripheral and central terminals. Here we demonstrate with
      the use of in vivo microdialysis and radioimmunoassay techniques that SP is also
      released within trigeminal ganglia following intraganglionic application of KCl,
      veratridine or capsaicin, and after electrical stimulation of peripheral afferent
      fibers. Both the basal and KCl-evoked release of SP are shown to be dependent on
      extracellular calcium. Using the turpentine-induced model of unilateral orofacial
      inflammation we also show that both the basal and KCl-evoked release of SP within
      trigeminal ganglia are greatly increased on the inflamed side 48 h after
      induction of inflammation. Coupled with previous demonstrations of excitatory
      effects of SP on sensory neurons, these results suggest that SP fulfils the role
      of a non-synaptically released diffusible chemical messenger that may modulate
      the somatic excitability of neurons within sensory ganglia in inflammatory pain
      states.

PMID- 10899286
TI  - Effects of pre-emptively administered nociceptin on the development of thermal
      hyperalgesia induced by two models of experimental mononeuropathy in the rat.
AB  - Pre-emptive analgesia is thought to be produced by the prevention of spinal
      facilitation evoked by nociceptive input to the spinal cord. Opioid receptor-like
      1 (ORL1) receptor agonist has been reported to inhibit the development of spinal
      facilitation. We investigated the effect of nociceptin, an ORL1 receptor agonist,
      on the development of thermal hyperalgesia and the expression of Fos-like
      immunoreactivity (Fos-LI) in the spinal dorsal horn induced by two neuropathic
      pain models, the chronic constriction injury model and the partial sciatic nerve
      injury model. Chronic constriction injury is created by placing four loosely tied
      ligatures around the right sciatic nerve. Partial sciatic nerve injury was
      created by tight ligation of one third to one half of the right sciatic nerve.
      All drugs were injected intrathecally 10 min before the nerve injury. The anti
      hyperalgesic effect of drugs was evaluated by the measurement of the paw
      withdrawal latency (PWL) against thermal nociceptive stimulation. The PWLs of the
      injured paws were measured 7, 14 and 21 days after the nerve injury. Expression
      of Fos-LI was examined 2 h after the nerve injury. Intrathecal injection of
      nociceptin significantly delayed the development of thermal hyperalgesia and
      decreased the expression of Fos-LI induced by chronic constriction injury, but
      not that induced by partial sciatic nerve injury. These data indicate that pre
      emptive administration of nociceptin might be one strategy for the prevention of
      the development of neuropathic pain.

PMID- 10899287
TI  - Effects of neonatal injury of the inferior alveolar nerve on the development and
      regeneration of periodontal nerve fibers in the rat incisor.
AB  - Our previous study showed that the migration of terminal Schwann cells occurred
      in the periodontal ligament of the rat lower incisor following transection of the
      inferior alveolar nerve (IAN) in the adult animals [Y. Atsumi, K. Matsumoto, M.
      Sakuda, T. Maeda, K. Kurisu, S. Wakisaka, Altered distribution of Schwann cells
      in the periodontal ligament of the rat incisor following resection of the
      inferior alveolar nerve: An immunohistochemical study on S-100 proteins, Brain
      Res. 849 (1999) 187-195]. The aim of the present study was to investigate the
      effects of neonatal transection of the IAN on the regeneration of axon elements
      and Schwann cells in the periodontal ligament of the rat lower incisor. Following
      transection of IAN at post-natal day 5 (PN 5d), when the numbers of both axon
      elements and the terminal Schwann cells were very small, regenerating nerve
      fibers appeared between post-injured days 7 (PO 7d) and PO 14d, and increased in
      number thereafter gradually. Although the terminal morphologies of regenerated
      Ruffini endings became identical to those of the adult animals by PO 54d, the
      number of regenerated PGP 9.5-IR nerve fibers did not recover the adult levels
      even by PO 56d. A small number of Schwann cells migrated into the shear zone, the
      border between the alveolus-related part (ARP) and the tooth-related part (TRP),
      but did not enter into the TRP. Following transection of the IAN at PN 14d or PN
      28d, when clusters of apparent terminal Schwann cells could be recognized, axon
      regeneration started around PO 5d. Individual axon terminals of the regenerating
      Ruffini endings ramified and became identical to those of the adult animals
      around PO 28d, but the number of regenerated Ruffini endings was smaller than
      that of the adult animals. Similar to the adult animals, the migration of Schwann
      cells into the shear zone and TRP occurred, and disappeared prior to the
      completion of the axonal regeneration. The present results indicate that the
      migration of the Schwann cells into TRP during the regeneration of the
      periodontal nerve fibers following nerve injury to the IAN depends on the
      maturation of the terminal Schwann cells of the periodontal Ruffini endings, not
      on post-operative time.

PMID- 10899288
TI  - Truncated TrkB mediates the endocytosis and release of BDNF and neurotrophin-4/5
      by rat astrocytes and schwann cells in vitro.
AB  - Binding and cross-linking studies with radiolabeled neurotrophins demonstrate
      that cultured rat hippocampal astrocytes lack full-length TrkB, but do express
      high levels of truncated TrkB (tTrkB). In astrocytes and Schwann cells, tTrkB
      appears to have the novel function of mediating the endocytosis of neurotrophins
      into an acid-stable, Triton X-100 resistant intracellular pool that is released
      back into the medium in a temperature-dependent manner. Chloroquine treatment,
      trichloroacetic acid solubility, and sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) analysis revealed that when incubated with astrocytes
      or Schwann cells for at least 48 h neither the intracellular nor the released
      neurotrophins were significantly degraded. The endocytosis and release of
      neurotrophins may represent a novel mechanism whereby neuroglia can regulate the
      local concentration of these neurotrophic factors for extended periods of time.

PMID- 10899289
TI  - Involvement of mGluR(5) on acute nociceptive transmission.
AB  - The effect of the mGluR(5) antagonist, MPEP (2-Methyl-6-(phenylethynyl)
      pyridine), and of the mGluR(1) antagonist, AIDA((RS)-1-Aminoindan-1,5
      dicarboxylic acid), were examined on nociceptive neurons in the
      ventroposterolateral (VPL) nucleus of the thalamus in response to pressure
      stimuli to the contralateral hindpaw of rats under urethane anesthesia.
      Intravenous (i.v.) injection of MPEP (0.1, 1, and 10 mg/kg) blocked responses to
      noxious stimulation in a dose-dependent and reversible manner. AIDA (3 and 15
      mg/kg, i.v.), in contrast, had no effect on these cells. MPEP action was
      selective to noxious stimulation because even when tested at the highest dose (10
      mg/kg, i.v.) it did not alter the responses of non-nociceptive neurons to brush
      stimulation. To investigate the site of action of MPEP, intra-thalamic injections
      were made during electrophysiological recordings. Using this method, the mGluR(5)
      antagonist did not affect nociceptive responses, suggesting that thalamic
      receptors were not involved in this action. On the other hand, the NMDA thalamic
      receptors seem to be involved because the NMDA receptor antagonist, MK801,
      successfully blocked responses to noxious pressure stimulation following intra
      thalamic injections. In the spinal cord in vitro model, MPEP (30 microM, 60 min)
      was also able to attenuate ventral root potentials after single shock electrical
      stimulation of the dorsal root and inhibit wind-up response evoked by repetitive
      stimulation. Taken together, these findings suggest that blockade of the
      mGluR(5), but not mGluR(1) decreases nociceptive transmission in the thalamus and
      that these effects may be mediated by spinal cord receptors.

PMID- 10899290
TI  - ARL 17477, a selective nitric oxide synthase inhibitor, with neuroprotective
      effects in animal models of global and focal cerebral ischaemia.
AB  - In the present studies, we have evaluated the effects of N-[4-(2-?[(3
      Chlorophenyl)methyl]amino?ethyl)phenyl]-2-thiophenecarbo ximidamide
      dihydrochloride (ARL 17477) on recombinant human neuronal NOS (nNOS) and
      endothelial NOS (eNOS). We then carried out pharmacokinetic studies and measured
      cortical nitric oxide synthase (NOS) inhibition to determine that the compound
      crossed the blood brain barrier. Finally, the compound was evaluated in a model
      of global ischaemia in the gerbil and two models of transient focal ischaemia in
      the rat. The IC(50) values for ARL 17477 on human recombinant human nNOS and eNOS
      were 1 and 17 microM, respectively. ARL 17477 (50 mg/kg i.p.) produced a
      significant reduction in the ischaemia-induced hippocampal damage following
      global ischaemia when administered immediately post-occlusion, but failed to
      protect when administration was delayed until 30 min post-occlusion. In the
      endothelin-1 model of focal ischaemia, ARL 17477 (1 mg/kg i.v.) significantly
      attenuated the infarct volume when administered at either 0, 1 or 2 h post
      endothelin-1 (P<0.05). In the intraluminal suture model, ARL 17477 at both 1 and
      3 mg/kg i.v. failed to reduce the infarct volume measured at 1, 3 or 7 days post
      occlusion. These results demonstrate that ARL 17477 protects against global
      ischaemia in gerbils and provides some reduction in infarct volume following
      transient middle cerebral artery occlusion in rats, indicating that nNOS
      inhibition may be a useful treatment of ischaemic conditions.

PMID- 10899291
TI  - Interactions between 18-methoxycoronaridine (18-MC) and cocaine: dissociation of
      behavioural and neurochemical sensitization.
AB  - The phenomenon of sensitization has been implicated in various aspects of drug
      addiction. As such, the present study determined the effects of a potential anti
      addictive agent, 18-methoxycoronaridine (18-MC; 40 mg/kg, IP, 19 h earlier), on
      the expression of sensitization following the repeated administration of cocaine
      (COC; five once daily injections of 15 mg/kg, IP) or saline. The effects of 18-MC
      on COC metabolism were also assessed. Compared to vehicle controls, 18-MC
      significantly enhanced the expression of COC-induced locomotion (0, 10, 20 and 40
      mg/kg, IP) in chronic COC treated rats only. In both acute and chronic COC rats,
      18-MC potentiated the stereotypy induced by higher COC doses (20 and 40 mg/kg,
      IP). In contrast, 18-MC abolished the sensitized dopamine (DA) response in the
      nucleus accumbens (NAC) to COC (20 mg/kg), without altering the DA response of
      acute COC rats. None of the interactions between 18-MC and COC appear to be
      related to alterations in COC metabolism as no effect of 18-MC pretreatment was
      observed on extracellular levels of COC or two of its metabolites,
      benzoylecogonine and norcocaine. From the present findings, it is concluded that
      the enhancement of COC-induced behaviour produced by 18-MC pretreatment is
      independent of effects on either COC pharmacokinetics or COC-induced alterations
      in DA transmission. However, given that 18-MC decreases the self-administration
      of COC in laboratory animals, it is proposed that the anti-addictive efficacy of
      18-MC might be related to an ability to selectively block the expression of
      sensitized extracellular levels of DA in the NAC in rats with previous COC
      experience.

PMID- 10899292
TI  - Recovery from methamphetamine induced long-term nigrostriatal dopaminergic
      deficits without substantia nigra cell loss.
AB  - After administration of methamphetamine (METH) (2x2 mg/kg, 6 h apart) to vervet
      monkeys, long term but reversible dopaminergic deficits were observed in both in
      vivo and post-mortem studies. Longitudinal studies using positron emission
      tomography (PET) with the dopamine transporter (DAT)-binding ligand, [11C]WIN
      35,428 (WIN), were used to show decreases in striatal WIN binding of 80% at 1
      week and only 10% at 1.5 years. A post-mortem characterization of other METH
      subjects at 1 month showed extensive decreases in immunoreactivity (IR) profiles
      of tyrosine hydroxylase (TH), DAT and vesicular monoamine transporter-2 (VMAT) in
      the striatum, medial forebrain bundle and the ventral midbrain dopamine (VMD)
      cell region. These IR deficits were not associated with a loss of VMD cell number
      when assessed at 1.5 years by stereological methods. Further, at 1.5 years, IR
      profiles of METH subjects throughout the nigrostriatal dopamine system appeared
      similar to controls although some regional deficits persisted. Collectively, the
      magnitude and extent of the dopaminergic deficits, and the subsequent recovery
      were not suggestive of extensive axonal degeneration followed by regeneration.
      Alternatively, this apparent reversibility of the METH-induced neuroadaptations
      may be related primarily to long-term decreases in expression of VMD-related
      proteins that recover over time.

PMID- 10899293
TI  - In vivo electrical activity of brainstem neurons in fetal rats during asphyxia.
AB  - To see changes in the activity and the sensitivity to glutamate of fetal brain
      neurons during asphyxia, the electrical activity of brainstem neurons was
      recorded extracellularly in fetal rats which were still connected with the dams
      by the intact umbilical cord. In urethan-anesthetized pregnant rats, fetal
      asphyxia (2-10 min) was induced by occluding the umbilical cord with a surgical
      clip, while reperfusion of the umbilical blood flow was performed by local
      application of a relaxant of blood vessels to the occlusion site. The spontaneous
      discharge of fetal brainstem neurons was suppressed for a long period of time by
      umbilical cord occlusion. The suppression of the firing occurred 48-150 (78+/-7)
      s after the start of umbilical cord occlusion, and lasted even after fetal
      cortical PO(2) recovered to control level after reperfusion. The changes occurred
      with a marked reduction in spike amplitude. A similar suppression was observed
      for the spikes induced by iontophoretic application of glutamate, although fetal
      brainstem neurons were extremely sensitive to glutamate before asphyxia. The
      suppression of the spontaneous spikes became more notable and longer when
      asphyxia was repeated. These findings suggest that the long-lasting suppression
      of fetal neurons during asphyxia may contribute to a reduction of cellular energy
      requirements in the fetal brain, thereby playing a role in the resistance of
      fetal neurons to brain damage caused by asphyxia. Furthermore, the reduced
      sensitivity of fetal neurons to glutamate during asphyxia may also contribute to
      prevent brain damage due to excitotoxity of glutamate.

PMID- 10899294
TI  - Changes in striatal dopamine D(2) receptors in relation to expression of and
      recovery from experimental parkinsonism.
AB  - Changes in dopamine D(2) receptor number in 1-methyl-4-phenyl-1,2,3, 6
      tetrahydropyridine (MPTP)-treated cats during various stages of experimental
      parkinsonism were examined. In the normal adult cat, D(2) receptors were
      expressed throughout the striatum. In symptomatic cats (assessed 7 days after the
      last MPTP administration), there was a slight elevation of D(2) receptors in all
      striatal regions. At 2 weeks after MPTP (animals still grossly symptomatic), D(2)
      receptor number was increased 60-75% above normal. At 3 weeks after MPTP (partial
      functional recovery), D(2) receptor number remained elevated at a level slightly
      less than that observed at 2 weeks. At 6 weeks after MPTP (full functional
      recovery), D(2) receptor levels were back to normal. Changes in D(2) receptor
      mRNA expression in the striatum essentially mirrored the changes in receptor
      number. Increases in D(2) receptor number and mRNA expression did not coincide
      with the onset of parkinsonian signs and peaked after the parkinsonism was
      established. Permanent reduction of parkinsonian signs corresponded to
      normalization of D(2) receptor number.

PMID- 10899295
TI  - Antibodies to the C-terminus of the beta-amyloid precursor protein (APP): a site
      specific marker for the detection of traumatic axonal injury.
AB  - Antibodies to the amyloid precursor protein (APP) are commonly used to detect
      traumatic axonal injury (TAI). Carried by fast anterograde axoplasmic transport,
      APP will pool at regions of impaired transport associated with TAI. Based
      primarily upon commercial antibody availability, previous studies have targeted
      the N-terminus of APP, which, with respect to antigen detection, is suboptimally
      located within anterogradely transported vesicles. Recently, antibodies to the
      APP C-terminus, located on the external surface of anterogradely transported
      vesicles, have become available, allowing for the exploration of their utility in
      detecting TAI. To this end, rats were subjected to an impact acceleration injury,
      surviving 30 min to 24 h post-injury. They were then perfused, their brains
      sectioned and prepared for dual label immunofluorescent microscopy, single label
      bright field microscopy, and electron microscopy (EM). Antibodies to the APP C
      terminus yielded the ready detection of intensely labeled TAI with significantly
      reduced diffuse background staining in comparison to antibodies to the APP N
      terminus in both dual label immunofluorescent and single label bright-field
      approaches. EM examination of antibodies to the APP C-terminus in TAI revealed
      intense labeling of pooled intra-axonal vesicular profiles, confirming the
      anterogradely transported vesicular source of the APP seen in TAI. Interestingly,
      in addition to providing a technically superior approach and new detailed
      information on the subcellular localization of APP, antibodies to the APP C
      terminus also proved more cost effective. Immunofluorescent studies of APP C
      terminus immunoreactivity involved 1/3 the cost of targeting the N-terminus,
      while bright field APP C-terminus studies were performed for 1/20 the cost.

PMID- 10899296
TI  - Nitric oxide synthase immunoreactivity in the rat hippocampus after status
      epilepticus induced by perforant pathway stimulation.
AB  - Nitric oxide has recently been implicated in mediation of neuronal excitotoxicity
      and damage. This study aimed at elucidating the changes in the expression of
      neuronal isoform of nitric oxide synthase (nNOS) in the hippocampus after status
      epilepticus induced by perforant pathway stimulation. nNOS-immunoreactivity (nNOS
      ir) and neuronal damage, assessed by silver staining, were evaluated separately
      in different hippocampal subfields 2 weeks after induction of status epilepticus.
      Perforant pathway stimulation resulted in an increase in the number of nNOS
      immunoreactive neurons in the stratum radiatum of the CA1 and CA3 subfields of
      the hippocampus proper, and the hilus of the dentate gyrus. The morphology and
      distribution of the nNOS-ir neurons resembled that of interneurons. No
      correlation of the number of nNOS-ir neurons to the neuronal damage score was
      observed. Our results suggest that status epilepticus provokes a de novo
      expression of nNOS protein, and the nNOS expressing neurons may be selectively
      resistant to epileptic brain injury.

PMID- 10899297
TI  - Blocking the glycine-binding site of NMDA receptors prevents the progression of
      ischemic pathology induced by bilateral carotid artery occlusion in spontaneously
      hypertensive rats.
AB  - This study was designed to investigate the participation of N-methyl-D-aspartate
      (NMDA) receptors in the progression of the pathology induced by bilateral carotid
      artery occlusion (BCAo) in spontaneously hypertensive rats (SHRs). We examined
      the effects of the selective NMDA receptor glycine-binding site antagonist SM
      18400 on the mortality rate, deterioration of neurological signs, and formation
      of brain edema in the SHR-BCAo model. SM-18400 (15 or 30 mg/kg) was administered
      via the tail vein immediately and 2 h after BCAo. Neurological signs were
      monitored continuously for 8 h after BCAo, and the mortality rates were followed
      for 5 days. All SM-18400-treated animals were still alive 5 h after BCAo, whereas
      38% of the animals died in the vehicle-treated group. The mortality rates of the
      SM-18400-treated groups were still lower than those of the vehicle-treated group
      5 days after BCAo. In addition, SM-18400 markedly prevented the deterioration of
      neurological signs. The water content of the telencephalon and
      diencephalon/mesencephalon in the vehicle-treated group, measured 3 h after BCAo,
      was significantly higher than in the sham-operated group. SM-18400 significantly
      inhibited the increase in water content in both regions in a dose-dependent
      manner. These findings suggest that NMDA receptors participate in the increase in
      the mortality rate, deterioration of neurological signs, and formation of brain
      edema following ischemic brain damage in the SHR-BCAo model, and that SM-18400
      can prevent ischemic insults.

PMID- 10899298
TI  - Cytoskeletal protein mRNA expression in the chick utricle after treatment in
      vitro with aminoglycoside antibiotics: effects of insulin, iron chelators and
      cyclic nucleotides.
AB  - In birds, spontaneous recovery of the hair cells of the inner ear can occur after
      damage induced by aminoglycoside antibiotics. The factors that influence this
      recovery and the process of hair cell regeneration itself have until recently
      been investigated largely by morphological and histological methods. The aim of
      this work was to use a molecular biological approach to the analysis of hair cell
      regeneration by measuring the changes that occur in expression of mRNA for hair
      cell-specific cytoskeletal proteins fimbrin and class III beta-tubulin, along
      with that for beta-actin, in the utricle of chicks after hair cell damage both in
      vitro and in vivo. Utricles were removed from 1-day-old chicks and incubated with
      the aminoglycoside antibiotics gentamicin or neomycin (both 1 mM), or chicks were
      injected intraperitoneally with 100 mg/kg gentamicin or neomycin for 4
      consecutive days. At the end of the treatment periods, total RNA was extracted
      from single utricles, reverse transcribed to cDNA and the cDNA amplified by PCR
      with primers for beta-actin, fimbrin and class III beta-tubulin. Co-amplification
      allowed quantitative comparison of mRNA between fimbrin, or class III beta
      tubulin and beta-actin from the same utricle. Both aminoglycosides, either after
      48 h in vitro or immediately after treatment in vivo, caused a significant
      decrease in the expression of fimbrin mRNA and class III beta-tubulin mRNA,
      relative to beta-actin mRNA, which itself increased. Light and electron
      microscopy confirmed that this corresponded to loss of, and damage to, hair
      cells. The relative expression of fimbrin and class III beta-tubulin mRNAs was
      partly restored almost to control levels 4 days after cessation of treatment in
      vivo and fully normalised by 4 weeks, by which time hair cells appeared normal.
      However, their relative expression remained depressed 4 days after removal of
      antibiotic in vitro. The iron chelator desferrioxamine (100 microM) in vitro
      prevented the aminoglycoside-induced reduction in relative expression of mRNA for
      both fimbrin and class III beta-tubulin. Neither insulin (5 microM) nor a
      combination of dibutyryl cyclic AMP (5 mM) and the phosphodiesterase inhibitor
      IBMX (0.5 mM) prevented the decrease in relative expression of the mRNAs for the
      hair cell-specific proteins, but both treatments allowed their partial recovery
      in vitro during the 4-day-period after removal of aminoglycoside. It is concluded
      that the cells of the sensory epithelium of the chick utricle subjected to
      aminoglycoside-induced damage undergo a process in which mRNA expression is
      switched away from the production of functional proteins and towards proteins
      necessary for structural re-organisation. The restoration of mRNA expression to a
      normal pattern is promoted by the growth factor insulin and by cyclic AMP.

PMID- 10899299
TI  - Role of brain angiotensin II in renal nerve inhibition elicited by volume
      expansion in the conscious rabbit.
AB  - Losartan (10 microg/25 microl) or vehicle was injected into the fourth brain
      ventricle prior to volume expansion (VE) with Haemaccel (2 ml/min for 30 min).
      RSNA was reduced by a maximum of 45% in response to the VE following vehicle and
      by 33% following losartan. There was no significant difference between the
      treatments in RSNA, nor in the blood pressure and heart rate responses. We
      conclude that endogenous angiotensin II does not make a major contribution to the
      reflex reduction in RSNA initiated by VE.

PMID- 10899300
TI  - The effect of acute citalopram on extracellular 5-HT levels is not augmented by
      lithium: an in vivo microdialysis study.
AB  - A substantial number of patients do not respond sufficiently to antidepressant
      drugs and are therefore often co-medicated with lithium as an augmentative
      strategy. Since lithium has been demonstrated to affect 5-HT neurotransmission,
      we examined the effect of acute and subchronic lithium on 5-HT levels after a
      challenge with citalopram. We found that subchronic administration of lithium
      increases extracellular 5-HT baseline level and decreases the extracellular 5
      HIAA baseline. However, we found no evidence that the effect of acute citalopram
      on extracellular 5-HT levels is augmented by acute or subchronic lithium.

PMID- 10899301
TI  - Oxidative signaling pathway for externalization of plasma membrane
      phosphatidylserine during apoptosis.
AB  - Active maintenance of membrane phospholipid asymmetry is universal in normal cell
      membranes and its disruption with subsequent externalization of
      phosphatidylserine is a hallmark of apoptosis. Externalized phosphatidylserine
      appears to serve as an important signal for targeting recognition and elimination
      of apoptotic cells by macrophages, however, the molecular mechanisms responsible
      for phosphatidylserine translocation during apoptosis remain unresolved. Studies
      have focused on the function of aminophospholipid translocase and phospholipid
      scramblase as mediators of this process. Here we present evidence that unique
      oxidative events, represented by selective oxidation of phosphatidylserine, occur
      during apoptosis that could promote phosphatidylserine externalization. We
      speculate that selective phosphatidylserine oxidation could affect
      phosphatidylserine recognition by aminophospholipid translocase and/or directly
      result in enzyme inhibition. The potential interactions between the anionic
      phospholipid phosphatidylserine and the redox-active cationic protein effector of
      apoptosis, cytochrome c, are presented as a potential mechanism to account for
      selective oxidation of phosphatidylserine during apoptosis. Thus, cytochrome c
      mediated phosphatidylserine oxidation may represent an important component of the
      apoptotic pathway.

PMID- 10899302
TI  - Structure of the Bordetella pertussis 1414 endotoxin.
AB  - The endotoxin (lipopolysaccharide) of Bordetella pertussis, the agent of whooping
      cough, consists of a lipid A linked to a highly branched dodecasaccharide
      containing several acid and amino sugars. The elucidation of the polysaccharide
      structure was accomplished by first analyzing the structures of fragments
      obtained by hydrolysis and nitrous deamination and then piecing the fragments
      together. The fine structure of the antigenic distal pentasaccharide, presented
      here, was determined by chemical analyses as well as by high-resolution nuclear
      magnetic resonance and mass spectrometry. The complete structure was
      reconstituted and confirmed by matrix-assisted laser desorption/ionization mass
      spectrometry. The following structure was derived from the combined experimental
      data:The detailed structure combined with previously reported serological data
      now allows the synthesis of its epitopes for potential vaccines.

PMID- 10899303
TI  - Tissue-specific expression of multiple mRNA variants of the mouse estrogen
      receptor alpha gene.
AB  - The isolation of five new mouse estrogen receptor alpha mRNA variants (mERalpha
      A, B, F1, F2 and H) is described. All of these transcripts are generated by
      alternative splicing and all encode the 66 kDa ERalpha protein that the
      previously identified mRNA C variant generates. However, these transcripts differ
      in their 5' untranslated regions. RT-PCR and S1 nuclease protection assays
      revealed a tissue- and sex-specific expression pattern of all variants. The C and
      F mRNA variants are the predominantly expressed mERalpha variants in mouse. The
      expression of mERalpha H mRNA is restricted to liver, although female mice
      produce around a five fold higher level of this transcript than males. Our
      results show that the mERalpha gene is a complex genomic unit in mice that
      exhibits alternative splicing which is regulated in a tissue-specific manner.

PMID- 10899304
TI  - Influence of the pK(a) value of the buried, active-site cysteine on the redox
      properties of thioredoxin-like oxidoreductases.
AB  - Thioredoxin constitutes the prototype of the thiol-disulfide oxidoreductase
      family. These enzymes contain an active-site disulfide bridge with the consensus
      sequence Cys-Xaa-Xaa-Cys. The more N-terminal active-site cysteine is generally a
      strong nucleophile with an abnormal low pK(a) value. In contrast, the more C
      terminal cysteine is buried and only little is known about its effective pK(a)
      during catalysis of disulfide exchange reactions. Here we have analyzed the pK(a)
      values of the active-site thiols in wild type thioredoxin and a 400-fold more
      oxidizing thioredoxin variant by NMR spectroscopy, using selectively (13)C(beta)
      Cys-labeled proteins. We find that the effective pK(a) of the buried cysteine
      (pK(b)) of the variant is increased, while the pK(a) of the more N-terminal
      cysteine (pK(N)) is decreased relative to the corresponding pK(a) values in the
      wild type. We propose two empirical models which exclusively require the
      knowledge of pK(N) to predict the redox properties of thiol-disulfide
      oxidoreductases with reasonable accuracy.

PMID- 10899305
TI  - Translocation of Akt/PKB to the nucleus of osteoblast-like MC3T3-E1 cells exposed
      to proliferative growth factors.
AB  - An active phosphatidylinositol 3-kinase (PI3K) has been shown in nuclei of
      different cell types. The products of this enzyme, i.e. inositides phosphorylated
      in the D3 position of the inositol ring, may act as second messengers themselves.
      Nuclear PI3K translocation has been demonstrated to be related to an analogous
      translocation of a PtdIns(3,4,5)P(3) activated PKC, the zeta isozyme. We have
      examined the issue of whether or not in the osteoblast-like clonal cell line
      MC3T3-E1 there may be observed an insulin-like growth factor-I- (IGF-I) and
      platelet-derived growth factor- (PDGF) dependent nuclear translocation of an
      active Akt/PKB. Western blot analysis showed a maximal nuclear translocation
      after 20 min of IGF-I stimulation or after 30 min of PDGF treatment. Both growth
      factors increased rapidly and transiently the enzyme activity of
      immunoprecipitable nuclear Akt/PKB on a similar time scale and after 60 min the
      values were slightly higher than the basal levels. Enzyme translocation was
      blocked by the specific PI3K inhibitor, LY294002, as well as cell entry into S
      phase. Confocal microscopy showed an evident increase in immunostaining intensity
      in the nuclear interior after growth factor treatment but no changes in the
      subcellular distribution of Akt/PKB when a LY294002 pre-treatment was
      administered to the cells. These findings strongly suggest that the intranuclear
      translocation of Akt/PKB is an important step in signalling pathways that mediate
      cell proliferation.

PMID- 10899306
TI  - Synchronous glucose-dependent [Ca(2+)](i) oscillations in mouse pancreatic islets
      of Langerhans recorded in vivo.
AB  - Using microfluorescence in combination with image-analysis techniques we
      monitored intracellular calcium ([Ca(2+)](i)) dynamics in mouse islets of
      Langerhans loaded with fura-2 and recorded in vivo. [Ca(2+)](i) oscillates in the
      glycaemias range 5-10 mM, the duration of the oscillations being directly
      proportional to the blood glucose concentration. The analysis of different areas
      within the same islet shows that [Ca(2+)](i) oscillations are synchronous
      throughout the islet. These results show that in vivo, individual islets of
      Langerhans behave as a functional syncytium and suggest the existence of
      secretory pulses of insulin.

PMID- 10899307
TI  - Water and potassium dynamics inside the KcsA K(+) channel.
AB  - Molecular dynamics simulations and electrostatic modeling are used to investigate
      structural and dynamical properties of the potassium ions and of water molecules
      inside the KcsA channel immersed in a membrane-mimetic environment. Two potassium
      ions, initially located in the selectivity filter binding sites, maintain their
      position during 2 ns of dynamics. A third potassium ion is very mobile in the
      water-filled cavity. The protein appears engineered so as to polarize water
      molecules inside the channel cavity. The resulting water induced dipole and the
      positively charged potassium ion within the cavity are the key ingredients for
      stabilizing the two K(+) ions in the binding sites. These two ions experience
      single file movements upon removal of the potassium in the cavity, confirming the
      role of the latter in ion transport through the channel.

PMID- 10899308
TI  - CDC6 interacts with c-Myc to inhibit E-box-dependent transcription by abrogating
      c-Myc/Max complex.
AB  - The c-myc oncogene product (c-Myc) is a transcription factor that dimerizes with
      Max and recognizes the E-box sequence. It plays key functions in cell
      proliferation, differentiation and apoptosis. It is generally thought that c-Myc
      transactivates genes encoding proteins essential to cell-cycle progression by
      binding to the E-boxes that control them. The functions of c-Myc are also thought
      to be modulated by its associated proteins, several of which have recently been
      identified. In this study, we found that c-Myc directly bound in vivo and in
      vitro to the N-terminal region of human CDC6, a component of the pre-replication
      complex, and that both co-localized in cell nuclei. CDC6 bound to the C-proximal
      region of c-Myc, thereby competing with Max on the E-box sequence and changing c
      Myc/Max heterodimer to a Max/Max homodimer. In consequence, the E-box-dependent
      transcription activity of c-Myc was abrogated. These results suggest that, in
      addition to its DNA replication activity, CDC6 also has a role as a
      transcriptional suppressor of c-Myc.

PMID- 10899309
TI  - Conservation of the 3'-untranslated region of the Rab1a gene in amniote
      vertebrates: exceptional structure in marsupials and possible role for
      posttranscriptional regulation.
AB  - The YPT1/RAB1 protein, a key regulator of the intracellular vesicle transport in
      eukaryotes, is highly conserved in function and amino acid sequence. Here we
      report that the most highly conserved nucleotide sequence of the Rab1a gene of
      amniote vertebrates corresponds to the 3'-untranslated region (3'-UTR) of the
      mRNA. Sequences of 27 species ranging from mammals to sauropsida are >91%
      identical in this region. Secondary structure prediction procedures applied to
      the 3'-UTR sequences between positions 750 and 984 and 1428 (mouse cDNA: Y00094),
      respectively, of the RAB1a mRNAs revealed families of alternative structures
      around nucleotide position 800 as recurrent features. The two hairpin loops are
      also predicted for marsupials, despite of their exceptional extension of the A
      rich sequence in between. Yet, sequence conservation is much higher than required
      to conserve secondary structure. Implications for posttranscriptional regulation
      and protein binding are discussed.

PMID- 10899310
TI  - STAM2, a new member of the STAM family, binding to the Janus kinases.
AB  - We here cloned a cDNA encoding STAM2, a new member of the STAM family, which
      contains an SH3 domain and ITAM. STAM2 like STAM1 is associated with Jak2 and
      Jak3, and involved in the signaling for DNA synthesis and c-myc induction
      mediated by IL-2 and GM-CSF. Co-expression of the SH3 deletion mutants of STAM1
      and STAM2 induces an additive effect on suppressing DNA synthesis upon
      stimulation with IL-2 and GM-CSF, suggesting that STAM1 and STAM2 exhibit
      compensatory effects on the signaling pathways downstream of Jak2 and Jak3 upon
      stimulation with GM-SCF and IL-2, respectively.

PMID- 10899311
TI  - Erv1p from Saccharomyces cerevisiae is a FAD-linked sulfhydryl oxidase.
AB  - The yeast ERV1 gene encodes a small polypeptide of 189 amino acids that is
      essential for mitochondrial function and for the viability of the cell. In this
      study we report the enzymatic activity of this protein as a flavin-linked
      sulfhydryl oxidase catalyzing the formation of disulfide bridges. Deletion of the
      amino-terminal part of Erv1p shows that the enzyme activity is located in the 15
      kDa carboxy-terminal domain of the protein. This fragment of Erv1p still binds
      FAD and catalyzes the formation of disulfide bonds but is no longer able to form
      dimers like the complete protein. The carboxy-terminal fragment contains a
      conserved CXXC motif that is present in all homologous proteins from yeast to
      human. Thus Erv1p represents the first FAD-linked sulfhydryl oxidase from yeast
      and the first of these enzymes that is involved in mitochondrial biogenesis.

PMID- 10899312
TI  - Up-regulation of gut-enriched kruppel-like factor by interferon-gamma in human
      colon carcinoma cells.
AB  - Interferon-gamma (IFN-gamma) induces growth arrest and apoptosis of tumor cells
      but the mechanisms for these functions are unknown. Recently, gut-enriched
      kruppel-like factor (GKLF) was found to possess similar biological properties.
      Treatment of HT-29 cells with IFN-gamma inhibited cell proliferation and induced
      apoptosis, the effect was found to associate with GKLF expression. IFN-gamma
      stimulates GKLF mRNA and protein levels in a dose- and time-dependent manner and
      this process is independent of p53, occurs rapidly and does not require de novo
      protein synthesis indicating that GKLF is an immediate-early IFN-gamma-responsive
      gene. Moreover, overexpression of GKLF results in similar effect as IFN-gamma
      suggesting that GKLF may function as a downstream target of IFN-gamma.

PMID- 10899313
TI  - Translocation of the interleukin-1 receptor-associated kinase-1 (IRAK-1) into the
      nucleus.
AB  - Interleukin-1 (IL-1) signal transduction involves the recruitment of the IL-1
      receptor-associated kinase-1 (IRAK-1). Subsequent signaling finally leads to
      nuclear translocation of NFkappaB. We here show that the association and
      autophosphorylation of IRAK-1 was already detectable 30 s after IL-1 stimulation
      of ECV 304 cells. Significant levels of IRAK-1 accumulated in the nucleus 30 min
      after IL-1 stimulation shown by Western blot analysis and confocal laser scanning
      microscopy. Nuclear transfer of IRAK-1 upon IL-1 stimulation was confirmed in the
      murine T cell line EL-4. This characterizes nuclear localization of IRAK-1 as a
      possibly essential event in the IL-1 signaling cascade.

PMID- 10899314
TI  - Do the extracellular enzymes cellobiose dehydrogenase and manganese peroxidase
      form a pathway in lignin biodegradation?
AB  - The extracellular enzyme manganese peroxidase is believed to degrade lignin by a
      hydrogen peroxide-dependent oxidation of Mn(II) to the reactive species Mn(III)
      that attacks the lignin. However, Mn(III) is not able to directly oxidise the non
      phenolic lignin structures that predominate in native lignin. We show here that
      pretreatment of a non-phenolic lignin model compound with another extracellular
      fungal enzyme, cellobiose dehydrogenase, allows the manganese peroxidase system
      to oxidise this molecule. The mechanism behind this effect is demethoxylation
      and/or hydroxylation, i.e. conversion of a non-phenolic structure to a phenolic
      one, mediated by hydroxyl radicals generated by cellobiose dehydrogenase. This
      suggests that cellobiose dehydrogenase and manganese peroxidase may act in an
      extracellular pathway in fungal lignin biodegradation. Analytical techniques used
      in this paper are reverse-phase high-pressure liquid chromatography, gas
      chromatography connected to mass spectroscopy and UV-visible spectroscopy.

PMID- 10899315
TI  - Density-dependent induction of TNF-alpha release from human monocytes by
      immobilized P-selectin.
AB  - P-selectin purified from human platelets, when immobilized on a solid surface,
      induced monocytes to release tumor necrosis factor-alpha (TNF-alpha). The
      induction of TNF-alpha release was dependent on the concentration of P-selectin
      used for the immobilization, and the maximal stimulation was observed when the
      plate was coated with 0.3 microgram/ml of P-selectin. Use of either a higher or a
      lower concentration of P-selectin for the plate-coating was found to elicit less
      TNF-alpha release, although the higher concentration of P-selectin caused a
      stronger adhesion of HL-60 leukemic cells. The expression of mRNA for TNF-alpha
      roughly paralleled the TNF-alpha secretion, as assessed by RT-PCR. These results
      indicate that monocytes are activated by immobilized P-selectin in a density
      dependent manner.

PMID- 10899316
TI  - Differential immediate-early gene responses to shear stress and intraluminal
      pressure in intact human conduit vessels.
AB  - We have previously shown distinct effects of shear stress and pressure on
      transcription of several potent vascular mediators. In the present study, we
      tested the hypothesis that c-jun and c-fos are regulated differentially by shear
      and pressure. Intact human umbilical veins were perfused with various
      combinations of shear and pressure during 1.5, 3 and 6 h. Protein and gene
      expressions were assessed by immunofluorescence and real-time reverse
      transcription PCR, respectively. Shear stress and pressure exert differential
      temporal effects on c-jun and c-fos gene and protein expression, and these
      immediate-early gene responses appear to be cell-type specific for endothelial
      and smooth muscle cells.

PMID- 10899317
TI  - Haemozoin formation in the midgut of the blood-sucking insect Rhodnius prolixus.
AB  - Malaria parasites digest haemoglobin and detoxify the free haem by its
      sequestration into an insoluble dark-brown pigment known as haemozoin (Hz). Until
      recently, this pigment could be found only in Plasmodium parasites. However, we
      have shown that Hz is also present in the midgut of the blood-sucking insect
      Rhodnius prolixus [Oliveira et al. (1999) Nature 400, 517-518]. Here we show that
      Hz synthesis in the midgut of this insect is promoted by a particulate fraction
      from intestine lumen. Haem aggregation activity is heat-labile and is inhibited
      in vitro by chloroquine (CLQ). Inhibition of Hz formation in vivo by feeding
      insects with CLQ leads to increased levels of haem in the haemolymph of the
      insect, which resulted in increased lipid peroxidation. Taken together, these
      results indicate that a factor capable of promoting Hz crystallisation is present
      in R. prolixus midgut and that this activity represents an important
      physiological defence of this insect against haem toxicity.

PMID- 10899318
TI  - Functional specificity conferred by the unique plasticity of fully alpha-helical
      Ras and Rho GAPs.
AB  - Structural comparisons of the two GTPase activating proteins (GAPs) p120 and p50
      in complex with Ras and Rho, respectively, allowed us to decipher the functional
      role of specific structural features, such as helix alpha8c of p120 and helix A1
      of p50, necessary for small GTPase recognition. We identified important residues
      that may be critical for stabilization of the GAP/GTPase binary complexes.
      Detection of topohydrophobic positions (positions which are most often occupied
      by hydrophobic amino acids within a family of protein domains) conserved between
      the two GAP families led to the characterization of a common flexible four-helix
      bundle. Altogether, these data are consistent with a rearrangement of several
      helices around a common core, which strongly supports the assumption that p50 and
      p120 GAPs derive from a unique fold. Considered as a whole, the remarkable
      plasticity of GAPs appears to be a means used by nature to accurately confer
      functional specificity.

PMID- 10899319
TI  - Cloning and characterization of rat casein kinase 1epsilon.
AB  - Genes differentially expressed in the subjective day and night in the rat
      suprachiasmatic nucleus (SCN) were surveyed by differential display. A gene
      homologous to human casein kinase 1epsilon (CK1epsilon) was isolated, which
      initially appeared to be expressed in the suprachiasmatic nucleus (SCN) in a
      circadian manner. We here describe the cDNA cloning of the rat CK1epsilon and
      characterization of the protein products. The rCK1epsilon is predominantly
      expressed in the brain including the SCN, binds and phosphorylates mPer1, mPer2,
      and mPer3 in vitro, and translocates mPer1 and mPer3, but not mPer2, to the cell
      nucleus depending on its kinase activity when coexpressed with these Per proteins
      in COS-7 cells.

PMID- 10899320
TI  - Evidence for the presence of a component of the Mn complex of the photosystem II
      reaction centre which is exposed to water in the S(2) state of the water
      oxidation complex.
AB  - The interaction of water oxidising photosystem II preparations with the aqueous
      environment has been investigated using electron spin echo envelope modulation
      spectroscopy in the presence of 2H(2)O. The spectra show interaction of 2H of
      2H(2)O with the preparation in the S(2) state. The component interacting with
      water decays during 1-4 weeks storage at 77 K. No interaction of water with the
      classical multiline S(2) Mn signal, which is more stable on storage at 77 K, was
      detected. The results show that a component of the water oxidation complex,
      possibly involving the Mn centre, is accessible to water and may be the water
      binding site for photosynthetic water oxidation.

PMID- 10899321
TI  - Homologous mutations in two diverse sulphate transporters have similar effects.
AB  - Mutations in the human sulphate transporter gene, DTDST, have been implicated in
      several diseases. Analysis of affected patients has linked disease symptoms to
      faulty sulphate transporter activity. We have reproduced two of these mutations
      in SHST1, a homologous member of the family isolated from the tropical legume,
      Stylosanthes hamata. Both mutations significantly reduce sulphate transport
      activity of SHST1. These results indicate that conserved residues between
      distinct members of the family may share essential roles in structure or
      function. The results also suggest that putative helix 9 may be important for
      stability and/or trafficking of SHST1 to the plasma membrane.

PMID- 10899322
TI  - The HIV-1 gp120 inhibits the binding of adenosine deaminase to CD26 by a
      mechanism modulated by CD4 and CXCR4 expression.
AB  - HIV-1 external envelope glycoprotein gp120 inhibits adenosine deaminase (ADA)
      binding to its cell surface receptor in lymphocytes, CD26, by a mechanism that
      does not require the gp120-CD4 interaction. To further characterize this
      mechanism, we studied ADA binding to murine clones stably expressing human CD26
      and/or human CD4, and transiently expressing human CXCR4. In this heterologous
      model, we show that both recombinant gp120 and viral particles from the X4 HIV-1
      isolate IIIB inhibited the binding of ADA to wild-type or catalytically inactive
      forms of CD26. In cells lacking human CXCR4 expression, this gp120-mediated
      inhibition of ADA binding to human CD26 was completely dependent on the
      expression of human CD4. In contrast, when cells were transfected with human
      CXCR4 the inhibitory effect of gp120 was significantly enhanced and was not
      blocked by anti-CD4 antibodies. These data suggest that the interaction of gp120
      with CD4 or CXCR4 is required for efficient inhibition of ADA binding to CD26,
      although in the presence of CXCR4 the interaction of gp120 with CD4 may be
      dispensable.

PMID- 10899323
TI  - Specific defects in double-stranded DNA unwinding and homologous pairing of a
      mutant RecA protein.
AB  - The DNA molecules bound to RecA filaments are extended 1.5-fold relative to B
      form DNA. This extended DNA structure may be important in the recognition of
      homology between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). In
      this study, we show that the K286N mutation specifically impaired the dsDNA
      unwinding and homologous pairing activities of RecA, without an apparent effect
      on dsDNA binding itself. In contrast, the R243Q mutation caused defective dsDNA
      unwinding, due to the defective dsDNA binding of the C-terminal domain of RecA.
      These results provide new evidence that dsDNA unwinding is essential to homology
      recognition between ssDNA and dsDNA during homologous pairing.

PMID- 10899324
TI  - Type I muscle atrophy caused by microgravity-induced decrease of myocyte enhancer
      factor 2C (MEF2C) protein expression.
AB  - To investigate the molecular mechanisms of muscle atrophy under microgravity, the
      paraspinal muscles of rats after 14 days spaceflight and those of ground-based
      controls were examined. In the microgravitational environment, expressions of 42
      genes changed, and the expressions of heat shock protein 70 and t complex
      polypeptide 1 increased. In Northern blotting, myocyte-specific enhancer binding
      factor 2C (MEF2C) and MEF2C-related genes including aldolase A and muscle ankyrin
      decreased. After 9 days ground recovery, expression of MEF2C increased and it was
      located mainly on the satellite cells in the muscle regeneration state. MEF2C
      could be a key transcriptional factor for skeletal muscle atrophy and
      regeneration under microgravity.

PMID- 10899325
TI  - Increase in the adenine nucleotide translocase content of duckling subsarcolemmal
      mitochondria during cold acclimation.
AB  - Intermyofibrillar and subsarcolemmal mitochondria were isolated from duckling
      gastrocnemius muscle. The adenine nucleotide translocase (ANT) content of
      subsarcolemmal mitochondria was found to be half of that present in
      intermyofibrillar mitochondria. In addition, cold acclimation resulted in a 1.7
      fold increase in subsarcolemmal mitochondrial ANT content, with intermyofibrillar
      mitochondrial ANT remaining constant. This change in mitochondrial ANT content
      correlates with the previously reported cold-induced change in the sensitivity of
      mitochondria to palmitate-inhibited ATP synthesis [Roussel et al. (1998) FEBS
      Lett. 439, 258-262]. It is suggested that the mitochondrial ANT content enhances
      or reduces the fatty acid uncoupling activity in tissue, depending on the
      energetic state of mitochondria.

PMID- 10899326
TI  - The pre-transmembrane region of the human immunodeficiency virus type-1
      glycoprotein: a novel fusogenic sequence.
AB  - We have investigated membrane interactions and perturbations induced by NH(2)
      DKWASLWNWFNITNWLWYIK-COOH (HIV(c)), representing the membrane interface
      partitioning region that precedes the transmembrane anchor of the human
      immunodeficiency virus type-1 gp41 fusion protein. The HIV(c) peptide bound with
      high affinity to electrically neutral vesicles composed of
      dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine and cholesterol
      (molar ratio, 1:1:1), and induced vesicle leakage and lipid mixing. Infrared
      spectra suggest that these effects were promoted by membrane-associated peptides
      adopting an alpha-helical conformation. A sequence representing a defective gp41
      phenotype unable to mediate both cell-cell fusion and virus entry, was equally
      unable to induce vesicle fusion, and adopted a non-helical conformation in the
      membrane. We conclude that membrane perturbation and adoption of the alpha
      helical conformation by this gp41 region might be functionally meaningful.

PMID- 10899327
TI  - Cross-bridge action: present views, prospects, and unknowns.
AB  - When the sliding filament hypothesis was proposed in 1953-1954, existing evidence
      showed that (1) contributions to tension were given by active sites uniformly
      distributed within each zone of filament overlap and (2) each site functioned
      cyclically. These sites were identified by electron microscopy as cross-bridges
      between the two filaments, formed of the heads of myosin molecules projecting
      from a thick filament and attaching to a thin filament. The angle of these cross
      bridges was found to be different at rest and in rigor, suggesting that the event
      causing relative motion of the filaments was a change of the angle of the cross
      bridges. At first, it seemed likely that the whole cross-bridge rotated about its
      attachment to actin, but when the atomic structures of actin and myosin were
      obtained by X-ray crystallography, a possible hinge was found between the
      "catalytic domain" which attaches to the actin filament and the "light-chain
      domain" which appears to act as a lever arm. Two attitudes of the lever arm are
      now well established, the transition between them being driven by a
      conformational change coupled to some step in the hydrolysis of ATP, but several
      recent observations suggest that this is not the whole story: a third attitude
      has been shown by X-ray crystallography; a non-muscle myosin has been shown to
      produce its working stroke in two steps; and there are suggestions that an
      additional displacement of the filaments is produced by a change in the attitude
      of the catalytic domain on the thin filament.

PMID- 10899328
TI  - Stretch-shortening cycle: a powerful model to study normal and fatigued muscle.
AB  - Stretch-shortening cycle (SSC) in human skeletal muscle gives unique
      possibilities to study normal and fatigued muscle function. The in vivo force
      measurement systems, buckle transducer technique and optic fiber technique, have
      revealed that, as compared to a pure concentric action, a non-fatiguing SSC
      exercise demonstrates considerable performance enhancement with increased force
      at a given shortening velocity. Characteristic to this phenomenon is very low EMG
      activity in the concentric phase of the cycle, but a very pronounced contribution
      of the short-latency stretch-reflex component. This reflex contributes
      significantly to force generation during the transition (stretch-shortening)
      phase in SSC action such as hopping and running. The amplitude of the stretch
      reflex component - and the subsequent force enhancement - may vary according to
      the increased stretch-load but also to the level of fatigue. While moderate SSC
      fatigue may result in slight potentiation, the exhaustive SSC fatigue can
      dramatically reduce the same reflex contribution. SSC fatigue is a useful model
      to study the processes of reversible muscle damage and how they interact with
      muscle mechanics, joint and muscle stiffness. All these parameters and their
      reduction during SSC fatigue changes stiffness regulation through direct
      influences on muscle spindle (disfacilitation), and by activating III and IV
      afferent nerve endings (proprioseptic inhibition). The resulting reduced stretch
      reflex sensitivity and muscle stiffness deteriorate the force potentiation
      mechanisms. Recovery of these processes is long lasting and follows the bimodal
      trend of recovery. Direct mechanical disturbances in the sarcomere structural
      proteins, such as titin, may also occur as a result of an exhaustive SSC exercise
      bout.

PMID- 10899329
TI  - Movement biomechanics goes upwards: from the leg to the arm.
AB  - The analysis of lower limb movements has been well established in biomechanics
      research and clinical applications for a long time. For these studies, powerful
      and very advanced tools have been developed to measure movement parameters and
      reaction forces. The main focus of interest aims towards gait movements while the
      understanding of the basic concepts is supported by numerous models. Definitions
      of physiological ranges and detection of pathological changes in movements open
      an increasingly valuable clinical field of application. If, however, the primary
      function of the upper extremities as highly variable and adaptive organ for
      manipulating tasks is the subject of interest, the situation becomes considerably
      more complex. The nature of free arm movements is completely different from being
      restricted, repeatable or cyclic as compared to gait. Therefore, the transfer of
      the knowledge and experience gained in lower extremity movement analysis to the
      analysis of upper extremities turns out to be difficult. A proposal for how to
      proceed in measurements, e.g. where to place the markers and how to calculate
      movements and angles of segments involved, will be discussed which results in the
      description of the joint movements of wrist, elbow and shoulder joint. The
      definition of the motion is a specific step in upper extremity motion analysis
      which is important in terms of repeatability and significance of the results. An
      example of assessing movement disorders in children with plexus lesion will
      illustrate the implications and the potential of upper extremity movement
      analysis in clinical applications.

PMID- 10899330
TI  - Studies of human locomotion: past, present and future.
AB  - The study of human locomotion and its applications are examined from a historical
      viewpoint. Several critical steps in the advancement of the discipline are
      considered in the context of addressing a particular need to answer fundamental
      questions regarding the process of human locomotion. In addition, changes in the
      methods of observation are discussed in terms of the advancement of the field. As
      an example, the application of a newly developed point cluster technique to
      reduce the artifact due to skin movement is described. The method was applied to
      a study of patients with anterior cruciate ligament (ACL) deficient knees. The
      results demonstrate that patients with ACL-deficient knees have significantly
      greater than normal anterior-posterior displacement of the femur relative to the
      tibia during walking. Many of the advancements in the tools for observation and
      interpretation have been driven by new demands on our fundamental knowledge.
      Future advancements in the study of human locomotion will likely be motivated by
      new treatment modalities that require an in depth understanding of the subtle
      complexities of human locomotion. Future directions are discussed in the context
      of new methods for reducing errors associated with skin movement combined with
      information obtained from other imaging methods, such as magnetic resonance
      imaging.

PMID- 10899331
TI  - From biomechanical theory to application in top sports: the klapskate story.

PMID- 10899332
TI  - The use of a force-controlled dynamic knee simulator to quantify the mechanical
      performance of total knee replacement designs during functional activity.
AB  - The experimental evaluation of any total knee replacement (TKR) design should
      include the pre-implantation quantification of its mechanical performance during
      tests that simulate the common activities of daily living. To date, few dynamic
      TKR simulation studies have been conducted before implantation. Once in vivo, the
      accurate and reproducible assessment of TKR design mechanics is exceedingly
      difficult, with the secondary variables of the patient and the surgical technique
      hindering research. The current study utilizes a 6-degree-of-freedom force
      controlled knee simulator to quantify the effect of TKR design alone on TKR
      mechanics during a simulated walking cycle. Results show that all eight TKR
      designs tested elicited statistically different measures of tibial/femoral
      kinematics, simulated soft tissue loading, and implant geometric restraint
      loading during an identical simulated gait cycle, and that these differences were
      a direct result of TKR design alone. Maximum ranges of tibial kinematics over the
      eight designs tested were from 0.8mm anterior to 6.4mm posterior tibial
      displacement, and 14.1 degrees internal to 6.0 degrees external tibial rotation
      during the walking cycle. Soft tissue and implant reaction forces ranged from 106
      and 222N anteriorly to 19 and 127N posteriorly, and from 1.6 and 1.8Nm internally
      to 3.5 and 5.9Nm externally, respectively. These measures provide valuable
      experimental insight into the effect of TKR design alone on simulated in vivo TKR
      kinematics, bone interface loading and soft tissue loading. Future studies
      utilizing this methodology should investigate the effect of experimentally
      controlled variations in surgical and patient factors on TKR performance during
      simulated dynamic activity.

PMID- 10899333
TI  - Effect of ageing and vision on limb load asymmetry during quiet stance.
AB  - Although the identification and characterization of limb load asymmetries during
      quiet standing has not received much research attention, they may greatly extend
      our understanding of the upright stance stability control. It seems that the limb
      load asymmetry factor may serve as a veridical measure of postural stability and
      thus it can be used for early diagnostic of the age-related decline in balance
      control. The effects of ageing and of vision on limb load asymmetry (LLA) during
      quiet stance were studied in 43 healthy subjects (22 elderly, mean age 72.3+/-4.0
      yr, and 21 young, mean age 23.9+/-4.8 yr). Postural sway and body weight
      distribution were recorded while the subject was standing on two adjacent force
      platforms during two 120 s trials: one trial was performed with the eyes open
      (EO), while the other trial was with the eyes closed (EC). The results indicate
      that LLA was greater in the old adults when compared with the young control
      subjects. The LLA values were correlated with the postural sway magnitudes
      especially in the anteroposterior direction. Eyes closure which destabilized
      posture resulted in a significant increase of body weight distribution asymmetry
      in the elderly but not in the young persons. The limb load difference between EO
      and EC conditions showed a significantly greater effect of vision on LLA in the
      elderly compared to the young subjects. The observed differences in the LLA may
      be attributed to the decline of postural stability control in the elderly. Ageing
      results in the progressive decline of postural control and usually the nervous
      system requires more time to complete a balance recovery action. To compensate
      for such a deficiency, different compensatory strategies are developed. One of
      them, as evidenced in our study, is preparatory limb unload strategy (a stance
      asymmetry strategy) which could significantly shorten reaction time in balance
      recovery.

PMID- 10899334
TI  - Interaction between series compliance and sarcomere kinetics determines internal
      sarcomere shortening during fixed-end contraction.
AB  - The interaction between contractile force and in-series compliance was
      investigated for the intact skeletal muscle-tendon unit (MTU) of Rana pipiens
      semitendinosus muscles during fixed-end contraction. It was hypothesized that
      internal sarcomere shortening is a function of the length-force characteristics
      of contractile and series elastic components. The MTUs (n=18) were dissected,
      and, while submerged in Ringer's solution, muscles were activated at nine muscle
      lengths (-2 to +6 mm relative to optimal length in 1 mm intervals), while
      measuring muscle force and sarcomere length (SL) by laser diffraction. The MTU
      was clamped either at the bone (n=6), or at the proximal and distal ends of the
      aponeuroses (n=6). Muscle fibers were also trimmed along with aponeuroses down to
      5-20 fibers and identical measurements were performed (n=6). The magnitude of
      shortening decreased as MTU length increased. The magnitude of shortening ranged
      from -0.08 to 0.3 microm, and there was no significant difference between delta
      SL as a function of clamp location. When aponeuroses were trimmed, sarcomere
      shortening was not observed at L(0) and longer. These results suggest that the
      aponeurosis is the major contributor to in-series compliance. Results also
      support our hypothesis but there also appear to be other factors affecting
      internal sarcomere shortening. The functional consequence of internal sarcomere
      shortening as a function of sarcomere length was to skew the muscle length
      tension relationship to longer sarcomere lengths.

PMID- 10899335
TI  - Effects of surface irregularities on flow resistance in differently shaped
      arterial stenoses.
AB  - The combined influence of an asymmetric shape and surface irregularities has been
      explored in a computational study of flow through arterial stenoses with 48%
      areal occlusion. Contrary to the conclusion of an earlier investigation, namely
      that the resistance to laminar flow through a stenosed artery is being reduced in
      the presence of surface irregularities, the present predictions demonstrate that
      the flow resistance is practically unaffected by surface irregularities at low
      Reynolds numbers, whereas an excess pressure drop up to 10% above that for a
      smooth stenosis is observed for higher Reynolds numbers. For a given areal
      occlusion, the flow resistance is reduced with increasing degree of stenosis
      asymmetry and this effect may more than outweigh the influence of surface
      irregularities. This effect is moreover prevailing throughout the entire range of
      Reynolds numbers considered.

PMID- 10899336
TI  - Influence of different approaches for calculating the athlete's mechanical energy
      on energetic parameters in the pole vault.
AB  - The purposes of this study were as follows: (1) To determine the differences
      between two- and three-dimensionally calculated energy of the athlete in the pole
      vault. (2) To determine the differences between CM energy and total body energy.
      (3) To examine the influence of these different approaches of calculating the
      athlete's energy on energetic parameter values during the pole vault. Kinematic
      data were gathered during the pole vault final of the track and field world
      championships in 1997. Two video cameras (50Hz) covered the last step of the
      approach including the pole plant and 2 cameras covered the pole phase up to bar
      clearance, respectively. Twenty successful jumps were analysed. The
      characteristics of the energy development is similar for the different
      approaches. Initial energy, energy at maximum pole bend and energy at pole
      release (primary parameters) show significant differences (p<0.05). The findings
      indicate that rotatory movements and movements relative to the CM have a larger
      influence on the primary parameters than movements apart from the main plane of
      movement. For analysing the energy exchange between the athlete and the elastic
      implement pole only the differences among the secondary parameters (initial
      energy minus energy at maximum pole bend, final energy minus energy at maximum
      pole bend) are needed (Arampatzis et al., 1997 Biomechanical Research Project at
      the Vth World Championships in Athletics, Athens 1997: Preliminary Report. New
      Studies in Athletics 13, 66-69). For those parameters the relative differences
      between the calculation approaches range only between 1.47 and 0.04%. This
      indicates that the influence of the different approaches for calculating the
      athlete's energy on the analysis of energy exchange is negligible.

PMID- 10899337
TI  - Slower speeds in patients with diabetic neuropathy lead to improved local dynamic
      stability of continuous overground walking.
AB  - Patients with diabetic peripheral neuropathy are significantly more likely to
      fall while walking than subjects with intact sensation. While it has been
      suggested that these patients walk slower to improve locomotor stability, slower
      speeds are also associated with increased locomotor variability, and increased
      variability has traditionally been equated with loss of stability. If the latter
      were true, this would suggest that slowing down, as a locomotor control strategy,
      should be completely antithetical to the goal of maintaining stability. The
      present study resolves these seemingly paradoxical findings by using methods from
      nonlinear time series analysis to directly quantify the sensitivity of the
      locomotor system to local perturbations that are manifested as natural kinematic
      variability. Fourteen patients with severe peripheral neuropathy and 12 gender-,
      age-, height-, and weight-matched non-diabetic controls participated. Sagittal
      plane angles of the right hip, knee, and ankle joints and tri-axial accelerations
      of the trunk were measured during 10 min of continuous overground walking at self
      selected speeds. Maximum finite-time Lyapunov exponents were computed for each
      time series to quantify the local dynamic stability of these movements.
      Neuropathic patients exhibited slower walking speeds and better local dynamic
      stability of upper body movements in the horizontal plane than did control
      subjects. The differences in local dynamic stability were significantly predicted
      by differences in walking speed, but not by differences in sensory status. These
      results support the hypothesis that reductions in walking speed are a
      compensatory strategy used by neuropathic patients to maintain dynamic stability
      of the upper body during level walking.

PMID- 10899338
TI  - Wear particle diffusion and tissue differentiation in TKA implant fibrous
      interfaces.
AB  - In the context of mechanical loosening, we studied the hypothesis that wear
      particle migration in the fibrous membrane under tibial plateaus after total knee
      arthroplasty can be explained by the pumping effects of the interstitial fluid in
      the tissue. Further, as a secondary objective we investigated the possibility
      that interface-tissue differentiation is influenced by interstitial fluid flow
      and strain, as mechanical effects of interface motions. For comparative reasons,
      we analyzed a previously published simplified two-dimensional finite-element
      model, this time assuming biphasic tissue properties. We wanted to determine
      hydrostatic pressure and flow velocities in the fluid phase, in addition to
      stresses and strains, for time-dependent loading of the plateau. We found that
      fluid flow in the interface was extremely slow, except in the periphery. Hence,
      loosening due to particle-induced bone resorption appears improbable. The
      results, however, do support the idea that particles migrate with fluid flow,
      when such flow occurs. Where fibrous tissue tends to be prominent in reality, the
      fluid is repeatedly extruded and reabsorbed in the model. Where these values are
      low, fibrocartilage is commonly found. When material properties were varied to
      subsequently represent fibrocartilage and two stages of mineralization, the
      strains and fluid velocities is reduced. Fluid pressure, however, did not change.
      Our results refute the hypothesis that wear particles are pumped through the
      interface tissue below a TKA but support the hypothesis that interface tissue
      type and loosening processes are influenced by mechanical tissue variables such
      as tissue strain and interstitial fluid velocity.

PMID- 10899339
TI  - Coronary stent implantation changes 3-D vessel geometry and 3-D shear stress
      distribution.
AB  - Mechanisms of in-stent restenosis are not fully understood. Shear stress is known
      to play a role in plaque and thrombus formation and is sensitive to changes in
      regional vessel geometry. Hence, we evaluated the regional changes in 3-D
      geometry and shear stress induced by stent placement in coronary arteries of
      pigs.Methods. 3-D reconstruction was performed, applying a combined angiographic
      and IVUS technique (ANGUS), from seven Wallstents (diameter 3.5 (n=3) and 5mm
      (n=4)), which were implanted in seven coronary arteries of five pigs. This 3-D
      geometry was used to calculate locally the curvature, while the shear stress
      distribution was obtained by computational fluid dynamics. Local changes in shear
      stress were obtained at the entrance and exit of the stent for baseline (0. 65+/
      0.22 ml/s) and hyperemic flow (2.60+/-0.86 ml/s) conditions. Results. After stent
      implantation, the curvature increased by 121% at the entrance and by 100% at the
      exit of the stent, resulting in local changes in shear stress. In general, at the
      entrance of the stent local maxima in shear stress were generated, while at the
      exit both local maxima and minima in shear stress were observed (p<0.05).
      Additionally, the shear stress at the entrance and exit of the stent were
      correlated with the local curvature (r: 0.30-0.84).Conclusion. Stent implantation
      changes 3-D vessel geometry in such a way that regions with decreased and
      increased shear stress occur close to the stent edges. These changes might be
      related to the asymmetric patterns of in-stent restenosis.

PMID- 10899340
TI  - Surface roughness parameters as predictors of anchorage strength in bone: a
      critical analysis.
AB  - The surface roughness of a bone implant was defined parametrically. The values of
      the parameters defining the surface were varied. Some traditionally used surface
      roughness parameters were calculated. By means of a theoretical model the bone
      implant interfacial shear strength was estimated. No simple correlation between
      the values of the surface roughness parameters and the estimated interfacial
      shear strength was found. It was concluded that the value of the traditional
      surface roughness parameters as predictors of interfacial shear strength is
      limited. If however a change of the surface topography of an implant is
      restricted to scale a positive correlation was found between the theoretical
      interfacial shear strength and some surface roughness parameters. It is suggested
      that the bone-implant interfacial shear strength in the general case be estimated
      by means of strength analyses based upon a study of the size, shape and density
      of the individual elements constituting the rough surface.

PMID- 10899341
TI  - Numerical simulation of flow fields in a tube with two branches.
AB  - In the present study, a numerical calculation procedure based on the finite
      volume method was employed to simulate flow fields in double-branched tubes. The
      configuration was a tube with two vertical branches; the two branches were either
      on the same side or on the opposite side. The study focused on the baseline flow
      fields and the possible flow interaction between the two branches. The branching
      ratio and the branch /main tube diameter ratio were fixed in this study. The
      results showed that when the two branches were on the same side, the
      low/oscillating shear regions were found on the ventral walls of the branches and
      on the dorsal wall of the main tube distal to the branches. The flow field
      proximal to each branch was similar to that in a single-branched tube when the
      two branches were distant. When the branches were on the opposite side with the
      staggering distance S=0 (symmetric case), the low/oscillating shear regions were
      found on the lateral walls of the main tube. As S increased, the interaction
      between the two branches weakened, the low/oscillating shear regions were found
      on the lateral walls of the main tube to the side of the second branch. The flow
      field near the branch was significantly different from that of a single-branched
      tube. Care should be taken on localization of plaques in multi-branched vessels
      due to the flow pattern change. The numerical results were qualitatively
      consistent with what observed experimentally, by other investigators.

PMID- 10899342
TI  - A sensitivity analysis of the calculation of mechanical output through inverse
      dynamics: a computer simulation study.
AB  - The purpose of this study was to systematically determine the effect of
      experimental errors on the work output calculated using two different methods of
      inverse dynamics during vertical jumping: (a) the conventional (rotational)
      method and (b) the translational method. A two-dimensional musculoskeletal model
      was used to generate precisely known kinematics. Next, the location of each joint
      center (JC) and the location of each segment's center of mass (CM) were
      manipulated by +/-10% of segment length to simulate errors in the location of
      joint centers (delta JC) and errors in the location of segment's center of mass
      (delta CM), respectively. Work output was subsequently calculated by applying the
      two methods of inverse dynamics to the manipulated kinematic data. The results
      showed that the translational method of inverse dynamics was less sensitive (up
      to 13% error in total work output) to delta JC and delta CM than the rotational
      method (up to 28% error in total work output). The rotational method of inverse
      dynamics was particularly sensitive to simulated errors in JC.

PMID- 10899343
TI  - A measure of kinematic limb instability modulation by rhythmic auditory
      stimulation.
AB  - A mathematical method based on computations of residual absolute value sums
      (RAVS) was developed for the quantitative analysis of tremor-like perturbations
      of knee angle during the gait cycle. The method was tested on simulation data
      created by adding sinusoidal tremor of varying frequency and amplitude to the
      knee-angle graph of a healthy test subject. The method was then applied to
      compare knee tremor reduction, with and without auditory rhythm, in a group of
      five traumatically brain-injured patients with gait hemiparesis. Deviations from
      normal gait performance due to tremor were assessed by using self-comparison to a
      17th-degree regression polynomial of each subject's own motion-, time-, and point
      normalized knee- angle curve. With rhythmic cueing, the five subjects had a
      statistically significant RAVS-measured mean tremor reduction of 39.5+/-22.6% (t=
      3.91; p=0.017).

PMID- 10899344
TI  - Critical evaluation of known bone material properties to realize anisotropic FE
      simulation of the proximal femur.
AB  - PURPOSE: In a meta-analysis of the literature we evaluated the present knowledge
      of the material properties of cortical and cancellous bone to answer the question
      whether the available data are sufficient to realize anisotropic finite element
      (FE)-models of the proximal femur. MATERIAL AND METHOD: All studies that met the
      following criteria were analyzed: Young's modulus, tensile, compressive and
      torsional strengths, Poisson's ratio, the shear modulus and the viscoelastic
      properties had to be determined experimentally. The experiments had to be carried
      out in a moist environment and at room temperature with freshly removed and
      untreated human cadaverous femurs. All material properties had to be determined
      in defined load directions (axial, transverse) and should have been correlated to
      apparent density (g/cm(3)), reflecting the individually variable and age
      dependent changes of bone material properties. RESULTS: Differences in Young's
      modulus of cortical [cancellous] bone at a rate of between 33% (58%) (at low
      apparent density) and 62% (80%) (at high apparent density), are higher in the
      axial than in the transverse load direction. Similar results have been seen for
      the compressive strength of femoral bone. For the tensile and torsional
      strengths, Poisson's ratio and the shear modulus, only ultimate values have been
      found without a correlation to apparent density. For the viscoelastic behaviour
      of bone only data of cortical bone and in axial load direction have been
      described up to now. CONCLUSIONS: Anisotropic FE-models of the femur could be
      realized for most part with the summarized material properties of bone if
      characterized by apparent density and load directions. Because several mechanical
      properties have not been correlated to these main criteria, further experimental
      investigations will be necessary in future.

PMID- 10899346
TI  - Dose-adjusted thrombosis prophylaxis in trauma surgery according to levels of D
      Dimer.
AB  - In 234 trauma surgery patients, thrombosis prophylaxis with Nadroparin-Calcium
      low-molecular-weight heparin (LMWH) was adjusted according to levels of D-Dimer.
      Basic prophylaxis was 2,850 IU per day. If D-Dimer concentrations rose above 2
      mg/L after the fourth postoperative (p.o.) day, LMWH was administered twice a
      day. Color Doppler ultrasound was performed between the fifth and seventh p.o.
      days. Patients were divided into a high-risk (group 1: hip, femur, or knee
      replacement surgery, n=102) and a moderate-risk group (group 2: other surgery of
      the knee, tibia, fibula, or foot, n=132). Group 1 showed significantly higher D
      Dimer levels than group 2 (p<0.001). Measurement of D-Dimer on days 2 and 4 p.o.
      showed a sensitivity of 100% and a specificity of 72.8% in identifying patients
      at risk (i.e., D-Dimer>2 mg/L after day 4 p.o.). The overall deep vein thrombosis
      (DVT) rate in group 1 was 3.9%, and the rate of proximal DVT was 1.96%. In group
      2, one distal DVT (0.8%) occurred. The results show that D-Dimer is a useful
      marker to monitor p.o. coagulation activation and to manage LMWH prophylaxis in
      trauma surgery patients.

PMID- 10899345
TI  - Correlation between different intensities of anti-vitamin K treatment and
      coagulation parameters.
AB  - In order to study the effect of different intensities of anti-vitamin K treatment
      on coagulation parameters, 23 patients with venous thromboembolism were given,
      after the initial treatment period, warfarin at doses giving an International
      Normalised Ratio of 1.3-2.0 for 4 weeks, and of 1.1-1.3 for another 4 weeks.
      Blood samples were taken at the end of each of these periods and 4 weeks after
      the end of warfarin treatment. The vitamin K-dependent coagulation factors VII,
      IX, and X, as well as the inhibitor protein C and its cofactor protein S, all
      showed a highly significant correlation with treatment intensity. This was to
      some extent also true for the coagulation activation markers, prothrombin
      fragment 1+2 and thrombin-antithrombin complex. Ratios of pro- and anticoagulant
      factors in some instances showed a decrease at therapeutical (International
      Normalised Ratio) levels, and also sometimes with reduced warfarin treatment
      intensity. Taken together, our results encourage further research addressing
      issues of varying treatment intensity with warfarin and alternative methods for
      monitoring of anti-vitamin K treatment.

PMID- 10899347
TI  - Increased D-dimer levels in twin gestation.
AB  - In normal pregnancy, the hemostatic balance is displaced toward
      hypercoagulability. The elevation in plasma levels of coagulation factors VII,
      VIII, and X and fibrinogen and the increased concentrations of plasminogen
      activator inhibitors [1,2] may predispose individuals to thromboembolism,
      especially near term [1,3]. Because human multifetal gestation requires still
      greater physiological alterations, the imbalance in hemostasis is further
      exaggerated. It has been suggested that the changes in the coagulation system
      near term may even mimic low-grade disseminated intravascular coagulopathy [4].
      However, for the majority of women with multifetal gestation, the coagulopathy
      observed in the laboratory is not clinically apparent [5]. Despite the large body
      of research on the physiological adaptation to pregnancy, relatively little is
      known of the biological adaptation in general and the hemostatic changes in
      particular associated with multiple gestation.

PMID- 10899348
TI  - Microvascular consequences of thrombosis in small venules: an in vivo microscopic
      study using a novel model in the ear of the hairless mouse.
AB  - Little is known of the development of chronic microvascular alterations following
      small vessel thrombosis, which is probably due to the lack of appropriate
      experimental models. Herein we report the first results on thrombosis-associated
      long-term changes of microvascular permeability and vessel tortuosity and
      diameter and blood perfusion using the ear of the hairless mouse, and intravital
      fluorescence microscopy. Thrombosis was induced photochemically in small venules
      (diameter: 75 to 100 microm) using light/dye exposure (fluorescein isothiocyanate
      dextran 150,000), and the microcirculation compromised by the blockade of blood
      drainage was analyzed before and 30 minutes after induction of thrombosis as well
      as repeatedly over a 28-day observation period. Thrombus formation resulted in a
      marked increase (p<0.05) of microvascular permeability (0.85+/-0.11) when
      compared with baseline values (0.46+/-0.04). Permeability remained elevated
      (p<0.05) at days 1 (0.67+/-0.07), 3 (0.58+/-0.02), and 7 (0.60+/-0.06), but
      returned to normal after 28 days (0.43+/-0.03). Tortuosity, diameter, and red
      blood cell velocity of venular segments, located upstream of thrombus formation,
      were found unchanged during the entire 28-day observation period. This was
      probably due to the fact that blood flow from the thrombosis-affected tissue was
      frequently drained into nonaffected tissue via preexisting "through-fare"
      channels, serving as venulo-venular collaterals. In accordance, in 10 to 20% of
      these venular segments the direction of blood perfusion was found changed, while
      those changes were only rarely observed in venular vessel segments of the
      nonthrombotic contralateral ears. We conclude that thrombosis in small cutaneous
      venules is primarily characterized by an increased vascular permeability,
      reflecting an inflammatory response, similar to what is known from
      thrombophlebitis in patients. The model presented herein may be a versatile tool
      to study pathogenesis of chronic microcirculatory derangements in microthrombosis
      and their prevention by novel therapeutic strategies.

PMID- 10899349
TI  - Comparative study of antithrombotic effect of a low molecular weight heparin and
      unfractionated heparin in an ex vivo model of deep arterial injury.
AB  - Thrombosis after plaque rupture triggers the onset of acute coronary events. The
      treatment of choice for patients with acute coronary syndromes is conventional
      unfractionated heparin. Low molecular weight heparin has recently been reported
      to be as effective and even safer than unfractionated heparin. In this study, the
      effects of the low molecular weight heparin reviparin and unfractionated heparin
      on thrombus formation were examined under dynamic conditions using an
      extracorporeal perfusion chamber in a porcine model. Thrombus formation was
      assessed by the deposition of porcine 123I-fibrin(ogen) and autologous 111In
      platelets on porcine tunica media at high and low shear rates. Reviparin reduced
      the fibrinogen molecules deposited on injured vessels at high shear rates (252+/
      80 molecules x 10(12)/cm2 for reviparine (200 U/kg/hour) vs. 624+/-70 x 10(12)/cm
      for unfractionated heparin (200 U/kg/hour) (p<0.05). At low shear rates,
      fibrinogen deposition was also significantly reduced by reviparin (130+/-15
      molecules x 10(12)/cm2) compared to unfractionated heparin (192+/-40 x 10(12)/cm2
      at 200 U/kg/hour; p<0.05). No change in platelet deposition was detected after
      heparin administration in either treatment group. In conclusion, the low
      molecular weight heparin reviparin has a higher antithrombotic potential than
      unfractionated heparin. Reviparin may have advantages over unfractionated heparin
      in treatment and prevention of acute coronary syndromes.

PMID- 10899350
TI  - Age-related changes in coagulation, fibrinolysis, and platelet aggregation in
      male WBN/Kob rats.
AB  - We investigated the age-related changes in blood coagulation, fibrinolysis, and
      platelet aggregation in male WBN/Kob rats, animals that exhibit spontaneously
      diabetes mellitus at more than 6 months of age. The rats aged 6 months or more
      showed significant hyperglycemia, hypoinsulinemia, and hyperlipidemia. As changes
      in coagulation parameters, the data indicated significant increases in factors
      II, V, VII, VIII, IX, X, and XII activities; a significant decrease in
      antithrombin III activity in rats more than 6 months of age; significant
      increases in fibrinogen level and factor XI activity; and significant decreases
      in prothrombin time and activated partial thromboplastin time in those more than
      9 months of age. As changes in fibrinolytic parameters, the animals showed
      significant decreases in plasminogen and tissue-type plasminogen activator, and
      significant increases in alpha2-plasmin inhibitor and plasminogen activator
      inhibitor at more than 6 months of age. In addition, there were significant
      correlations between the plasma levels of coagulation/fibrinolytic markers and
      the 4-hour fasting glucose or lipids. Furthermore, they displayed significant
      increases in ADP- or collagen-induced platelet aggregation and in
      cholesterol/phospholipid molar ratio in platelets at more than 9 months of age.
      The increase in cholesterol/phospholipid ratio may be responsible for
      hyperaggregation of platelets in diabetic animals. These findings suggest that
      WBN/Kob rats are suitable for research on blood coagulation abnormalities in
      diabetes. However, further studies are needed to clarify the details of the
      mechanisms involved.

PMID- 10899351
TI  - Hemodynamic changes and systemic activation of coagulation and fibrinolysis
      during controlled endotoxemia in pigs.
AB  - In this study, we have established a pig model that can combine extensive
      hemodynamic monitoring with simultaneous repetitive (serial) blood sampling for
      the study of multiple variables related to the hemostatic system. Sixteen healthy
      young pigs were studied to evaluate the influence of continuous endotoxin
      infusion on hemodynamic patterns and activation of coagulation and fibrinolysis.
      The chief aim of the study was to investigate the applicability of analytical
      methods primarily developed for use with human plasma samples in quantification
      of factors and reaction products of the porcine coagulation and fibrinolytic
      systems, and further, to use these methods to study the longitudinal changes in
      the plasma levels of these hemostatic variables as a consequence of endotoxin
      infusion. We found that acute, controlled endotoxemia induced a hemodynamic state
      of shock and reduced pulmonary gas exchange. Simultaneously, a gradual increase
      in peripheral blood mononuclear cell tissue factor activity was demonstrated, and
      increased maximally 5.5-fold 4 hours after onset of endotoxin infusion. Thrombin
      antithrombin complexes increased in plasma to maximum levels after 3 hours,
      accompanied by an ethanol gelation test that was regularly positive after 1 to 2
      hours, and fibrin monomer levels that gradually increased maximally 3.8-fold
      after 6 hours. These changes were followed by gradual decreases of both
      fibrinogen and factor VII levels, mainly due to consumption. Plasma levels of
      tissue type plasminogen activator activity peaked at 1.5 hours (11.3-fold
      increase), whereas the peak of plasminogen activator inhibitor-1 activity (14
      fold increase at 4.5 hours) was delayed compared to tissue plasminogen activator
      and completely extinguished plasma tissue plasminogen activator activity. The
      sequential activation of coagulation and fibrinolysis established a procoagulant
      state favoring disseminated intravascular coagulation and microthrombus
      formation, potentially leading to multiple organ dysfunction.

PMID- 10899352
TI  - Antithrombotic efficacy of single subcutaneous administration of a recombinant
      nematode anticoagulant peptide (rNAP5) in a canine model of coronary artery
      thrombolysis.
AB  - We examined the adjunctive benefit of recombinant nematode anticoagulant peptide
      (rNAP5), a factor Xa inhibitor, in a canine model of recombinant (rt)-PA-induced
      thrombolysis. In anesthetized dogs, a stable occlusive thrombus was formed by
      electrolytic injury of the vessel wall, after which the animals were administered
      rt-PA (1.44 mg/kg, i.v.) and rNAP5 (0.1 mg/kg, s.c.: n=13), or rt-PA plus vehicle
      (1-2 ml, s.c.; n=13). Hemodynamic and coagulation parameters were monitored for
      360 minutes. Single subcutaneous administration of rNAP5 resulted in a prolonged
      and sustained increase in the activated partial thromboplastin time (>100-fold),
      whereas prothrombin time was unchanged. The template bleeding time was not
      altered significantly throughout the protocol (maximum 1.4-fold). The incidence
      of reperfusion was similar in the two groups with a trend toward faster
      reperfusion in the rNAP5 group (34+/-4 minutes) compared to the vehicle group
      (63+/-15 minutes; p=0.07). After reperfusion, 80% of the vessels in the vehicle
      group reoccluded, whereas only 14% of vessels reoccluded in the rNAP5-treated
      group. Times to reocclusion were 65+/-21 minutes and 221+/-28 minutes,
      respectively (p<0.05). Single subcutaneous administration of rNAP5 sustained the
      coronary artery blood flow after reperfusion, such that at the end of protocol
      the flow was 47% of the preocclusion value as compared to the vehicle group in
      which the flow was 11% (p<0.05). Cyclic flow reductions were most prominent
      during rt-PA-induced reperfusion and were similar in both groups. The results
      indicate that a single subcutaneous administration of rNAP5 provides a sustained
      antithrombotic effect in maintaining the coronary artery patency during rt-PA
      induced thrombolysis.

PMID- 10899353
TI  - Singlet oxygen ((1)O2) inactivates plasmatic free and complexed alpha2
      macroglobulin.
AB  - alpha2-macroglobulin (alpha2M) is a broad-spectrum proteinase inhibitor and one
      of the major plasma proteins in humans. Activated phagocytes (especially
      granulocytes) generate large amounts of oxidants of the HOCI- and chloramine-type
      that release the mild nonradical, excited (light-emitting) oxidant singlet oxygen
      ((1)O2). These oxidants have been shown to inactivate several specific serine
      protease inhibitors in human blood [e.g., alpha1-antitrypsin or alpha2
      antiplasmin (plasmin inhibitor)]. The studies reported here demonstrate that
      nonradical oxidants also inactivate plasmatic alpha2M. The effective dose for 50%
      inactivation (ED50) of plasmatic alpha2M is similar to that for plasmatic alpha2
      antiplasmin. Chloramines are about 1,000-fold more effective than hydrogen
      peroxide (ED50)=0.75 micromol chloramine T/50 microl plasma). Serine protease
      serine protease inhibitor complexes are resistant to oxidants. In contrast, here
      it is shown that alpha2-macroglobulin, even after binding to serine proteases is
      sensitive to oxidation, the captured protease is released from the
      protease/alpha2M complex. This is the first time that oxidative inactivation of a
      complexed (i.e., bound to a target protease) human protease inhibitor has be
      shown. The (1)O2 inhibitors methionine, cysteine, cystine, or ascorbate-in
      contrast to the oxy-radical scavengers mannitol, superoxide dismutase, or
      catalase-antagonize the chloramine/NaOCl-mediated inactivation of both
      uncomplexed and complexed alpha2M. Thus, the oxidant involved here is of
      nonradicalic nature and has reaction characteristics of (1)O2. For the inhibitory
      function, critical oxidizable methionines or the internal thiol-ester might be
      targets for (1)O2. Consequently, alpha2M can also be considered a carrier for
      proteases, since the alpha2M-complexed proteases regain full activity in an
      oxidative environment. In local areas of inflammation or thrombolysis, activated
      phagocytes could create microenvironments of uncontrolled protease activity by
      generation of (1)O2.

PMID- 10899354
TI  - Microparticle-containing oncotic solutions augment in-vitro clot disruption by
      ultrasound.
AB  - Echocardiographic contrast agents enhance blood clot disruption by ultrasound. It
      has been suggested that the microbubbles add nuclei for the enhancement of
      cavitation by ultrasound. However, microbubbles are rapidly destroyed by the
      ultrasound energy. We assessed whether non-gas filled colloidal solutions
      (hyperoncotic medium molecular hydroxyethyl starch and degraded gelatin
      polypeptides) will facilitate clot disruption by ultrasound. In two separate
      experiments human blood clots, 200-400 mg in weight, were weighed and then
      immersed for 15 seconds in 10 ml normal saline solution containing 0%, 0.1%, 1%,
      2%, and 5% of hyperoncotic medium molecular hydroxyethyl starch or 0%, 0.035%,
      0.175%, 0.35%, and 0.7% degraded gelatin polypeptides. Clots were randomized to
      10 seconds 20 kHz ultrasound or immersion without ultrasound. After treatment,
      the clots were reweighed, and the percent difference in weight was calculated.
      Non-gas filled microparticle-containing solutions such as hyperoncotic medium
      molecular hydroxyethyl starch and degraded gelatin polypeptides significantly
      augmented blood clot disruption by ultrasound. The effect is dependent on the
      colloidal solution concentration with maximal effect achieved with 1%
      hyperoncotic medium molecular hydroxyethyl starch and 0.35% degraded gelatin
      polypeptides.

PMID- 10899355
TI  - The kinetic and structural characterization of the reaction of nafamostat with
      bovine pancreatic trypsin.
AB  - Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, is active
      against a number of the serine proteases involved in coagulation. This has been
      proposed as the basis of its anticoagulant activity. We investigated the reaction
      of Nafamostat with bovine pancreatic trypsin as a model system. It was shown to
      act as a time-dependent competitive inhibitor, and the inhibition constants for
      the binding of Nafamostat to trypsin (i.e., Ki) and the overall inhibition
      constants (i.e., Ki*) were calculated to be 11.5 microM and 0.4+/-0.14 nM,
      respectively. The second-order rate constant for the reaction was 4.5+/
      0.19x10(5) M(-1)s(-1), and the product released following the acylation step, 6
      amidino2-naphthol, showed mixed-type inhibition. The competitive (Kic) and
      uncompetitive (Kiu) inhibition constants were 14.7 microM and 19.5 microM,
      respectively. Formation of the acyl-enzyme intermediate was dissected into at
      least two steps, with rates of 0.9 s(-1) and 195 s(-1). The deacylation step was
      relatively much slower (3.2+/-0.19x10(-5) s(-1), enabling the mass spectroscopic
      analysis of the acyl-enzyme intermediate, which confirmed the covalent attachment
      of 4-guanidinobenzoic acid to trypsin. The product of the deacylation step, 4
      guanidinobenzoic acid, showed no inhibition up to a concentration of 200 microM.
      These data strongly suggest that while Nafamostat is a potent inhibitor of
      trypsin, it is actually an extremely poor substrate, and that apparent inhibition
      is due to the competitive formation of a very stable acyl-enzyme intermediate,
      analogous to some other active site titrants.

PMID- 10899356
TI  - Home-made anticoagulation monitor vs. CoaguCheck-Plus monitoring of oral
      anticoagulation.

PMID- 10899357
TI  - Lead and ethanol coexposure: implications on the dopaminergic system and
      associated behavioral functions.
AB  - The present investigation involves ethanol's effects on the lead-induced
      alterations in the dopaminergic system. Ethanol, at a dose of 3 g/kg body weight
      for 8 weeks, resulted in a marked increase in the accumulation of lead in the
      blood and brain of animals receiving 50 mg lead/kg body weight. Levels of
      dopamine were found to decrease significantly, and were accompanied with
      increased norepinephrine levels in lead and ethanol coexposed animals. Uptake of
      tyrosine as well as the activities of tyrosine hydroxylase and monoamine oxidase
      were seen to increase significantly in lead as well as ethanol-treated animals,
      and these were increased to a greater extent when animals were administered lead
      and ethanol simultaneously. Dopamine receptor binding studies revealed a
      significant elevation in the number of binding sites in lead and ethanol
      coexposed animals. The altered dopaminergic functions were reflected by the
      neurobehavioral deficits in terms of motor incoordination, aggressiveness, and
      hyperactivity of animals exposed to lead, the effect being more pronounced in
      lead- and ethanol-coexposed animals. In brief, results of this study suggests
      that ethanol potentiates lead-induced cellular damage at the neurochemical and
      neurobehavioral level.

PMID- 10899358
TI  - Time course of pharmacodynamic and pharmacokinetic effects of physostigmine
      assessed by functional brain imaging in humans.
AB  - In imaging studies of brain functions using pharmacological probes,
      identification of the time point at which central effects of intravenously
      infused drugs become stable is crucial to separate the effects of experimental
      variables from the concomitant changes in drug effects over time. We evaluated
      the time courses of the pharmacokinetics and pharmacodynamics, including
      butyrylcholinesterase inhibition and central neural responses, of physostigmine
      in healthy young subjects. Ten positron emission tomography (PET) scans that
      alternated between a rest condition (eyes open, ears unplugged) and a working
      memory for faces (WM) task were acquired in healthy subjects. Subjects in the
      drug group received a saline infusion for the first two scans, providing a
      baseline measure, then received an infusion of physostigmine for all subsequent
      scans. Subjects in the control group received a placebo infusion of saline for
      all scans. Physostigmine plasma levels and percent butyrylcholinesterase
      inhibition increased over time (p < 0. 0001), and both became stable by 40 min.
      Physostigmine decreased reaction time (RT) (p = 0.0005), and this effect was
      detected after 20 min of infusion and stable thereafter. Physostigmine also
      decreased regional cerebral blood flow (rCBF) in right prefrontal cortex during
      task (p = 0.0002), and this effect was detected after 40 min of infusion and
      stable thereafter. No change in RT or rCBF was observed in the control group.
      These results indicate that a 40-min infusion of physostigmine was necessary to
      obtain stable central effects. More generally, we have demonstrated that
      experimental effects can vary with time, especially during the initial phases of
      a drug infusion, indicating that it is critical that these changes are
      controlled.

PMID- 10899359
TI  - MDMA stimulus generalization to the 5-HT(1A) serotonin agonist 8-hydroxy-2- (di-n
      propylamino)tetralin.
AB  - The abused substance N-methyl-1-(3, 4-methylenedioxyphenyl)-2-aminopropane, or
      MDMA, serves as a training drug in animals. Because the 5-HT(1A) receptor
      antagonist NAN-190 has been shown to partially antagonize the MDMA stimulus, and
      because NAN-190 binds at several different types of receptors, in the present
      study we examined other agents (e.g., adrenergic, dopaminergic, sigma) in tests
      of stimulus generalization and stimulus antagonism to determine their influence
      on the MDMA stimulus. Each of these agents (i.e., clenbuterol, S(-)propranolol,
      R(+)SCH-23390, amantadine, NANM) was without effect on MDMA-appropriate
      responding. The finding that NAN-190 behaves as a 5-HT(1A) partial agonist in
      some studies prompted examination of the 5-HT(1A) receptor agonist 8-OH DPAT and
      its optical isomers. MDMA-stimulus generalization occurred to racemic 8-OH DPAT
      (ED(50) = 0.3 mg/kg), R(+)8-OH DPAT (ED(50) = 0.2 mg/kg), and to the 5-HT(1A)
      receptor partial agonist S(-)8-OH DPAT (ED(50) = 0.4 mg/kg). The results suggest
      that the MDMA stimulus might possess a 5-HT(1A) component of action. Furthermore,
      because 8-OH DPAT is known to enhance the stimulus effects of hallucinogens as
      discriminative stimuli, and because MDMA reportedly enhances the effects of
      hallucinogenic agents in humans ("flipping," "candy flipping"), this latter MDMA
      induced phenomenon might involve a 5-HT(1A) mechanism.

PMID- 10899360
TI  - Stimulus effects of phenylpropanolamine optical isomers in (+)amphetamine-trained
      rats.
AB  - There are eight phenylpropanolamine optical isomers related in structure to the
      central stimulants methamphetamine and amphetamine. Some of these are quite well
      known, such as (-)ephedrine, whereas others are relatively obscure, such as (
      )cathine. Although certain of these phenylpropanolamines, such as (-)ephedrine
      and (+)cathine, retain central stimulant activity and are about 10- to 25-fold
      less potent than (+)amphetamine, the eight phenylpropanolamines have been
      compared only once before in drug discrimination studies. This latter study
      employed (-)ephedrine as the training drug. Because there are striking
      similarities between (-)ephedrine and (+)amphetamine as training drugs, it was of
      interest to determine and compare the effect of all eight phenylpropanolamines in
      (+)amphetamine trained animals. Using rats trained to discriminate 1 mg/kg of
      (+)amphetamine from saline vehicle under a variable interval 15-s (VI 15-s)
      schedule of reinforcement, the (+)amphetamine stimulus generalized only to (
      )ephedrine (ED(50) = 4. 5 mg/kg) and (+)cathine (ED(50) = 8.0 mg/kg), and both
      agents were at least 10 times less potent that (+)amphetamine (ED(50) = 0.37
      mg/kg). These results stand in contrast to those obtained with the (-)ephedrine
      trained animals where the ephedrine stimulus generalized to all of the
      phenylpropanolamines except for (-)pseudoephedrine and (-)cathine. It is
      concluded that although there might be some similarity between the (-)ephedrine
      and (+)amphetamine stimuli, there are clear differences between them as
      determined in tests of stimulus generalization under the conditions employed.

PMID- 10899361
TI  - Prenatal nicotine exposure: effects on locomotor activity and central [125I]alpha
      BT binding in rats.
AB  - Maternal smoking during pregnancy or in utero exposure of the fetus to nicotine
      may result in learning difficulties and hyperactivity in the child. To elucidate
      possible involvement of the alpha(7) nicotinic receptor subtype in these
      behavioral impairments, pregnant dams were treated with nicotine (9 mg/kg/day)
      via osmotic minipumps throughout gestation. Male offspring were weaned at
      postnatal day 18, and were tested for locomotor activity at postnatal days 20-24.
      Pups were sacrificed on postnatal day 36-38 and 18 discrete brain areas were
      analyzed for [125I]alpha-bungarotoxin (alpha-BT) binding by quantitative
      autoradiography. Prenatal nicotine caused an elevation in locomotor activity
      (vertical movements) in offspring. [125I]alpha-BT binding was significantly
      reduced in the hippocampal CA1 region (29%), dentate gyrus (22%), and medial
      geniculate nucleus (29%). These findings suggest that some of the behavioral
      abnormalities induced by prenatal nicotine exposure may be due to a reduction of
      alpha(7) nicotinic receptors in discrete brain regions.

PMID- 10899362
TI  - MDMA and learning: effects of acute and neurotoxic exposure in the rat.
AB  - In two experiments, the effects of MDMA on the acquisition of lever-press
      responding of rats were examined under procedures in which water delivery was
      delayed by 0, 10, or 20 s relative to the response that produced it. In the first
      study, experimentally naive, water-deprived rats received an intraperitoneal
      injection of MDMA (0, 1.0, 3.2, or 5.6 mg/kg) prior to one 8-h experimental
      session. Response acquisition was observed under all conditions at all drug
      doses. MDMA increased the total number of responses emitted and the total number
      of water deliveries earned in dose-dependent fashion, but only when reinforcement
      was immediate. Under conditions of delay, MDMA had no effect on either measure.
      Under all reinforcement conditions, higher doses of MDMA typically produced an
      initial reduction in lever pressing, and in that sense interfered with learning.
      In the second study, rats received an MDMA injection regimen previously shown to
      be neurotoxic. Control rats received saline solution according to the same
      injection schedule. Two weeks after completing the regimen, rats were water
      deprived and exposed to behavioral procedures as described for the first
      experiment. Although MDMA significantly reduced 5-HT and 5-HIAA levels in the
      striatum and prefrontal cortex, mean performance of rats exposed to MDMA did not
      differ from that of rats exposed to vehicle. Twenty-five percent of the rats
      exposed to MDMA and delayed reinforcement did fail to acquire responding, which
      suggests that further study of the effects of neurotoxic doses of MDMA on initial
      response acquisition is warranted.

PMID- 10899363
TI  - Acute effects of d-amphetamine during the early and late follicular phases of the
      menstrual cycle in women.
AB  - Recent preclinical evidence indicates that ovarian hormones, such as estrogen and
      progesterone, may influence the behavioral effects of psychoactive drugs by
      interacting directly with neurotransmitter systems in the central nervous system.
      However, few studies have examined the effects of ovarian hormones on subjective
      or behavioral responses to psychoactive drugs in humans. In the present study, we
      assessed the subjective and physiological effects of d-amphetamine during the
      early and late follicular phases of the menstrual cycle. Nineteen healthy,
      regularly-cycling women participated in four sessions receiving doses of d
      amphetamine (AMPH; 15 mg oral) or placebo during the early and late follicular
      phases of two menstrual cycles. During the early follicular phase levels of both
      estrogen and progesterone are low, whereas during the late follicular phase
      estrogen levels are higher while progesterone remains low. Dependent measures
      included self-report questionnaires, physiological measures and plasma hormone
      levels. Most of the subjective and physiological effects of AMPH were not
      affected by menstrual cycle phase. However, subjects reported greater Unpleasant
      Stimulation after AMPH, and less Unpleasant Sedation, during the late follicular
      phase than during the early follicular phase. These results provide limited
      evidence that higher levels of estrogen during the late follicular phase alter
      the subjective effects of AMPH in normal, healthy women.

PMID- 10899364
TI  - Further characterization of the discriminative stimulus effects of spiradoline.
AB  - The results of a previous study in rats indicated that spiradoline has
      pharmacologically selective discriminative effects that are mediated by kappa
      opioid receptors. However, the training dose, 3.0 mg/kg, increased response
      latencies, suggesting that it was relatively high. The current study was
      performed to characterize further the discriminative effects of spiradoline by
      using a lower training dose, 1.0 mg/kg, and testing a larger number of drugs for
      generalization with spiradoline. Rats were trained in a discrete-trial
      avoidance/escape procedure to discriminate 1.0 mg/kg spiradoline, SC, from saline
      in an average of 19.7 sessions; response latencies after saline and spiradoline
      were not different from each other. The rats generalized dose dependently and
      completely to other kappa-opioid agonists that have relatively high efficacy:
      ethylketocyclazocine, U69,593, and U50,488. They generalized partially to
      ketocyclazocine, (-)-N-allylnormetazocine, and DuP 747, and not at all to
      cyclazocine, butorphanol, nalorphine, and pentazocine, discriminable opioids that
      have relatively low efficacy at kappa-opioid receptors, or to morphine and
      dextromethorphan, discriminable drugs that do not act at kappa-opioid receptors.
      The discriminative effects of spiradoline were unaffected by the mu-opioid
      antagonist beta-funaltrexamine, but were blocked completely for at least 4 weeks
      by the kappa-opioid antagonist nor-binaltorphimine. Thus, spiradoline-like
      stimulus control of behavior remains kappa-opioid selective, and continues to
      have a high efficacy requirement even at a training dose that does not impair
      performance.

PMID- 10899365
TI  - Altered regulation of dopaminergic activity and impairment in motor function in
      rats after subchronic exposure to styrene.
AB  - Animal and human studies suggest a dopamine-mediated effect of styrene
      neurotoxicity. However, the results reported to date are incomplete and not
      consistent. As such, the mechanism of its neurotoxicity is still unclear. The
      present study has, therefore, reexamined the central dopaminergic system in
      relation to some neurobehavioral effects in rats following subchronic exposure to
      styrene. Groups of adult male Sprague-Dawley rats received 0, 0.25, or 0.5 g
      styrene per kg b.wt. by gavage for 13 consecutive weeks. Twenty-four hours after
      cessation of such treatment with the higher dose (0.5 g/kg), the contents of
      dopamine (DA) and its metabolites were significantly reduced in the corpus
      striatum, hypothalamus, and lateral olfactory tract regions. In vitro styrene
      showed a significant increase in DA release from rat striatal synaptosomes
      similar to that of tyramine. Significant loss of motor function was observed on
      days 56, 70, and 84 during the styrene treatment with the higher dose, and lasted
      over a month after such treatment. However, the treated animals recovered their
      motor function within 45-60 days after cessation of such treatment, along with
      the recovery of normal levels of dopamine and its metabolites. Furthermore,
      styrene-induced initial impairments in measures of dopaminergic activity cannot
      be attributed to altered regulation of tyrosine hydroxylase activity. Specific
      [3H]-spiroperidol binding was also unaltered 7 or 15 days after subchronic
      treatment with styrene. These data imply that despite the dopaminergic neuronal
      loss due to styrene, dopaminergic transmission was not reduced to a level that
      would result in an overall development of dopamine receptor supersensitivity in
      the striatum. Collectively, these studies indicate that the subchronic neurotoxic
      action of styrene may be primarily presynaptic in nature and may involve impaired
      regulation of DA content and stimulation of DA release.

PMID- 10899366
TI  - The delayed effects of DTG and MK-801 on latent inhibition in a conditioned taste
      aversion paradigm.
AB  - The delayed effects of phencyclidine (PCP) have been shown to disrupt latent
      inhibition (LI) in a conditioned taste-aversion paradigm. In an attempt to
      understand the mechanism of this disruption, the delayed effects of the selective
      sigma receptor agonist 1,3-Di(2-tolyl)guanidine (DTG) and the selective NMDA
      receptor antagonist MK-801 on latent inhibition were assessed in the same
      paradigm. Water-deprived male rats were allowed access to either water
      (nonpreexposed; NPE) or 5% sucrose (preexposed; PE) for 30 min on 2 consecutive
      days. On the third day, animals were allowed access to sucrose and subsequently
      injected with lithium chloride. On the forth day, animals were allowed access to
      both sucrose and water. LI was assessed by comparing the percent sucrose consumed
      in PE and NPE groups on the fourth day. DTG (1.0, 5.0, or 10.0 mg/kg), MK-801
      (0.5, 1.0, or 2.0 mg/kg), or vehicle was administered IP 20 h before preexposure
      (days 1 and 2) and conditioning (day 3). In vehicle-treated groups, PE animals
      consumed a significantly higher percent sucrose on the test day than NPE animals,
      indicating the presence of LI. DTG (10.0 mg/kg) and MK-801 (2.0 mg/kg) decreased
      the percent sucrose consumed by animals in the PE group to the level observed in
      the NPE group, indicating disrupted LI. However, this dose of MK-801 was found to
      produce a decrease in percent sucrose consumed in PE animals not treated with
      lithium chloride, indicating that the decrease observed in the LI paradigm could
      be due to MK-801-induced decrease in taste preference for sucrose rather than a
      disruption of LI. Lower doses of MK-801 that did not produce a decrease in taste
      preference for sucrose did not significantly disrupt LI. None of the doses of DTG
      tested altered taste preference for sucrose. These data suggest a role for sigma
      receptors in the previously observed PCP-induced disruption of LI. Published by
      Elsevier Science Inc., 2000

PMID- 10899367
TI  - Effects of serotonergic agents on the transport response in rats.
AB  - In two experiments, researchers investigated the effects of manipulating
      serotonin systems on the transport response and dorsal immobility response in
      developing rats. In Experiment 1, administration of ketanserin and cinanserin,
      but not metergoline, suppressed the transport response in 23-day-old rats. These
      agents were without effect on dorsal immobility durations. In Experiment 2,
      administration of quipazine to 30-, 40-, and 50-day-old rats resulted in
      significant increases in transport response intensities and dorsal immobility
      durations. Results are discussed with respect to the nature of the transport
      response.

PMID- 10899368
TI  - Ketamine blocks a taste-mediated conditioned motor response in perinatal rats.
AB  - Brain N-methyl-D-aspartate (NMDA) glutamate receptors have been implicated as
      important mediators of both learning and neuronal development. The current study
      investigated how ketamine HCl (a well-known NMDA-receptor blocking drug) would
      influence taste-mediated conditioned motor responses in perinatal rats. Dams
      pregnant with E19 rat fetuses were injected with 0, 50, or 100 mg/kg ketamine HCl
      (IP). One-half hour later, a reversible spinal block was performed on the dam,
      and fetuses received an oral injection of 10 microl 0.3% Saccharin (SAC) or water
      while in utero. After the oral injection, fetuses received either saline or LiCl
      (81 mg/kg, IP). The uterus was replaced and, 2 days later (E21), rats received
      oral lavage with SAC. Rats in other litters were born via a normal vaginal
      delivery and were exposed to SAC on postnatal day 3 (P3). Observations of motor
      responses were recorded immediately after the oral lavage of SAC. If SAC had been
      paired with LiCl in utero, both E21 and P3 pups exhibited a conditioned
      suppression of orofacial movements (compared to controls). Both doses of ketamine
      significantly attenuated this taste-mediated conditioned motor response. These
      data reinforce the current conception of the fetus and neonate as sophisticated
      sensors and responders to the uterine and extrauterine environment. Further, our
      findings indicate a role for NMDA receptors in the formation of a conditioned
      motor response in fetal rats.

PMID- 10899369
TI  - Nicotine blood levels and subjective craving for cigarettes.
AB  - This study examined cigarette craving and blood nicotine levels in 11 male heavy
      smokers who were observed during 16 h of tobacco abstinence. Subjects rated their
      urge to smoke on a new brief 10-item questionnaire, Urge to Smoke (UTS), Schuh
      and Stitzer's four-item Visual Analog Scale (SSI), and a Strength of Urge to
      Smoke (SUTS) item. Testing occurred: 1) after 16 h (1700 h the night before to
      0900 h the next morning) of abstinence from smoking; 2) after an ad lib smoking
      period following the 16 h abstinence; 3) every hour during 6 hours of abstinence;
      4) and finally, after the 6 h abstinence, another ad lib smoking period. Thus,
      subjects smoked twice in each session. Blood plasma nicotine levels were measured
      before, after, and every 2 h during the 6-h abstinence period for a total of six
      measures. Blood pressure and heart rate were measured prior to each blood draw.
      There was a significant negative correlation between blood nicotine levels and
      craving for cigarettes on all craving questionnaires (rs = -0.55 to -0.78; ps <
      0.002). Carbon monoxide was shown to correlate highly with nicotine blood levels
      (rs = 0.83 to 0.98 across subjects; ps < 0.001). Results are consistent with the
      hypothesis that "urge to smoke" reflects nicotine seeking in continuing smokers.

PMID- 10899370
TI  - Reinstatement of both a conditioned place preference and a conditioned place
      aversion with drug primes.
AB  - In two experiments, we report that the place-conditioning paradigm can be used to
      demonstrate reinstatement of place preference/aversion by a drug prime following
      extinction training. In Experiment 1, rats were trained to prefer a chamber
      paired with morphine. Following extinction training, a morphine drug prime
      reinstated the morphine place preference. In Experiment 2, a lithium-induced
      conditioned place aversion was reinstated following extinction training by a
      lithium prime prior to testing. These results indicate that not only do rewarding
      drug primes produce reinstatement of learned responses (as demonstrated in the
      drug self-administration paradigm), but also aversive drug primes reinstate
      aversive learned responses.

PMID- 10899371
TI  - Naltrexone alteration of acute smoking response in nicotine-dependent subjects.
AB  - There are mixed results on the effects of opioid antagonists on acute nicotine
      response in humans. The present study examined the effects of a single dose of 50
      mg oral naltrexone relative to placebo on smoking response in 22 chronic smokers
      during short-term nicotine abstinence, after acute smoking and subsequent smoking
      deprivation, and on smoking behavior in a choice paradigm. The results showed
      that naltrexone significantly reduced immediate postcigarette ratings of smoking
      craving and desire to smoke and increased light-headedness, dizziness, and head
      rush (ps < 0.05). Reductions in craving and smoking desire persisted during a
      subsequent 1 h nonsmoking interval. Naltrexone also was found to significantly
      reduce the total number of cigarettes smoked in the choice interval, which was
      supported by objective measures of both reduced CO and plasma nicotine levels (ps
      < 0.01). Exploratory analyses on potential individual difference factors revealed
      that smokers with the highest levels of craving during abstinence showed the most
      pronounced naltrexone attenuation of smoking response. The results support the
      continued exploration of naltrexone as an adjunct to smoking cessation,
      especially in identified smoker subgroups most sensitive to the effects of opioid
      antagonism.

PMID- 10899372
TI  - Effect of the dopamine D(1/5) antagonist SCH 23390 on the acquisition of
      conditioned fear.
AB  - The authors previously reported that typical and atypical antipsychotic drugs
      inhibited the acquisition but not expression of conditioned fear. The present
      study examined the effects of the selective dopamine D(1/5) agonist (SKF 38393)
      and antagonist (SCH 23390) on the acquisition and expression of conditioned fear.
      Drugs were administered subcutaneously to male Sprague-Dawley rats 30 min before
      foot shock (2.5 mA for 5 min). Twenty-four hours after foot shock, rats were
      again placed and observed in the shock chamber without shocks (conditioned fear).
      Freezing behavior induced by conditioned fear, an index of anxiety or fear, was
      recorded using a time-sampling procedure. SCH 23390 (0.1-1 mg/kg) inhibited the
      acquisition of conditioned freezing. The administration of SCH 23390 at a dose of
      0.1 mg/kg 30 min after foot shock did not affect conditioned freezing. Taken
      together, it is concluded that D(1/5) antagonism inhibits the acquisition of
      conditioned fear. SKF 38393 (3-20 mg/kg) failed to change the acquisition of
      conditioned fear. SCH 23390 or SKF 38393 administered prior to testing did not
      reduce the expression of conditioned fear. These results suggest that D(1/5)
      receptors may play a role in the development of fear or anxiety.

PMID- 10899374
TI  - Dexamethasone reverses the ethanol-induced anxiolytic effect in rats.
AB  - The effects of intraperitoneal and intrahippocampal administration of the
      glucocorticoid dexamethasone were assessed regarding ethanol-induced anxiolysis
      in the elevated plus-maze in rats. Animals pretreated with systemic injections of
      dexamethasone (0.5, 1. 0, or 2.0 mg/kg, IP) 15 min before ethanol (1.2 g/kg, 14%
      w/v, IP) administration showed a significant dose-dependent attenuation of the
      increased percentage of frequency and time spent on open arms of the maze.
      However, IP dexamethasone treatment 4 h before the test had no effect. Unilateral
      intrahippocampal injection of dexamethasone (2 and 20 nmol in 0.5 microl) also
      significantly attenuated the increased exploration of the open arms induced by
      ethanol. The results are interpreted in terms of the modulation of the anxiolytic
      effects of ethanol by glucocorticoids and the possible involvement of hippocampus
      in this response. The rapid blockade of ethanol induced anxiolysis by
      dexamethasone strengthens the suggestion that a nongenomic mechanism may underlie
      this response.

PMID- 10899373
TI  - Effects of dopamine, NMDA, opiate, and serotonin-related agents on acute
      methamphetamine-induced self-injurious behavior in mice.
AB  - We examined the biochemical processes responsible for acute methamphetamine (MAP)
      induced self-injurious behavior (SIB) in mice. In initial experiments, a single
      dose of MAP (5, 10, or 15 mg/kg, IP) or an equivalent volume of saline was
      administered to male BALB/c mice. Acute MAP administration dose dependently
      increased the incidence of SIB (p < 0.05). In further experiments, we evaluated
      the effects of SCH23390, sulpiride, MK-801, naloxone or 5-hydroxy-L-tryptophan (5
      HTP) on the incidence of acute MAP (15 mg/kg, IP)-induced SIB. Both SCH23390 (0.5
      and 1.0 mg/kg, IP) and 5-HTP (100 and 200 mg/kg, IP) reduced the incidence of MAP
      induced SIB (p < 0.05). MK-801 (0.125 and 0.25 mg/kg, IP) completely blocked the
      SIB induced by MAP (p < 0.001). In contrast, neither sulpiride (25, 50, and 100
      mg/kg, IP) nor naloxone (1, 5, and 10 mg/kg, IP) affected the incidence of MAP
      induced SIB. It is concluded that dopamine D(1), NMDA, and serotonin
      neurotransmission may be involved in critical biochemical processes responsible
      for acute MAP-induced SIB.

PMID- 10899375
TI  - Increases in sucrose consumption, but not ethanol consumption, following ICV NPY
      administration.
AB  - Neuropeptide Y (NPY) is a centrally acting neuromodulator that influences both
      consummatory behaviors and anxiety. NPY's effects on feeding are primarily
      regulated through Y5 receptors in hypothalamic sites, whereas NPY-induced
      anxiolysis appears to be mediated by Y1 receptors in the amygdala. Recently, NPY
      has been postulated to play a role in the regulation of ethanol consumption. The
      present study assessed the influence of intracerebroventricular (ICV)
      administration of NPY on the consumption of 10% ethanol or 2% sucrose in rats.
      Male Wistar rats were trained to self-administer 10% ethanol using the sucrose
      substitution procedure and then implanted with an intracerebroventricular (ICV)
      cannula. The effects of NPY (0-15 microg) on ethanol consumption and sucrose
      consumption were then examined. ICV NPY infusion had no significant effects on
      the consumption of 10% ethanol, however, NPY significantly increased the
      consumption of 2% sucrose, [F(1, 11) = 6.18, p = 0.03]. These data suggest that
      ethanol intake and sucrose intake are differentially regulated by NPY. It is
      hypothesized that ICV infusion of NPY may be affecting both Y1 and Y5 receptors
      producing increased consummatory drive and anxiolysis, two factors that have
      opposing effects on subsequent ethanol consumption. Therefore, additional studies
      including site specific injection of NPY will be necessary to provide further
      insight into the role of NPY on ethanol consumption.

PMID- 10899376
TI  - Antagonistic effect of pseudoginsenoside-F11 on the behavioral actions of
      morphine in mice.
AB  - The antagonistic effect of pseudoginoside-F11 (PF(11)) on the various actions of
      morphine was studied in mice. The results demonstrated that PF(11), at the doses
      of 4 and 8 mg/kg, PO, significantly inhibited morphine (10 mg/kg, SC)-induced
      memory impairment in the Morris water maze test. PF(11), at 4 mg/kg, PO, did not
      influence conditioned place preference per se, yet markedly blocked the
      conditioned place preference to morphine. PF(11), at the doses of 4 and 8 mg/kg,
      PO, also significantly antagonized morphine (5 mg/kg, SC)-induced analgesia
      tested by tail pinch method. PF(11), at 4 mg/kg, PO, did not influence locomotor
      activity per se, yet inhibited the development of the reverse tolerance, as shown
      by the increase in locomotor activity, to morphine. At the doses of 4 and 8
      mg/kg, PO, PF(11) significantly antagonized the development of analgesia
      tolerance to morphine in the tail pinch test. Thus, the above results demonstrate
      for the first time that PF(11) can antagonize some actions of morphine. However,
      the mechanism of action of PF(11) merits further evaluation.

PMID- 10899377
TI  - Heroin-induced suppression of saccharin intake in water-deprived and water
      replete rats.
AB  - Rats suppress intake of a saccharin conditioned stimulus (CS) when paired with an
      aversive unconditioned stimulus such as lithium chloride. This phenomenon is
      referred to as a conditioned taste aversion (CTA). Rats also suppress intake of a
      saccharin CS when paired with a rewarding sucrose solution and when paired with a
      drug of abuse. Although the suppressive effects of drugs of abuse have long been
      interpreted as CTAs, evidence suggests that rats may suppress intake of the
      saccharin CS following taste-drug pairings because they are anticipating the
      rewarding rather than the aversive properties of the drug. Oddly, however, while
      all other drugs of abuse tested suppress intake of a gustatory CS, the highly
      reinforcing drug, heroin, is reportedly ineffective. The present study reexamined
      this issue in both water-deprived and water-replete rats using procedures that
      sustain both morphine- and cocaine-induced suppression of CS intake. The results
      showed that heroin greatly reduced CS intake following saccharin-heroin pairings
      and that this effect was less variable when assessed in water-replete subjects.
      When taken with other reports, these data suggest that rats suppress intake of a
      saccharin CS in anticipation of the availability of all drugs of abuse tested.

PMID- 10899378
TI  - Serotonin reuptake is less efficient in taste aversion resistant than in taste
      aversion-prone rats.
AB  - We have previously reported the development of rat lines bred selectively for
      differences in taste aversion conditionability. Earlier studies demonstrated that
      the taste aversion resistant (TAR) animals exhibited lower concentrations of
      brain serotonin and consumed greater amounts of ethanol than their taste aversion
      prone (TAP) counterparts. In the present study, TAR rats demonstrated
      significantly less efficient brain serotonin transport compared to TAP rats, but
      the rat lines demonstrated similar levels of serotonin transporter or V(max) and
      similar whole brain paroxetine (a specific serotonin reuptake inhibitor) binding
      (B(max)). These results suggest that the rat lines differ in the mechanisms that
      transport serotonin into nerve endings, but do not differ in the binding of
      serotonin to the transporter or in the number of serotonin transport sites. The
      data support the hypothesis that genetically determined differences in the
      serotonin system contribute to individual differences in taste aversion
      conditionability. The findings further suggest that differences in serotonin
      transport may influence the propensity to self-administer ethanol.

PMID- 10899379
TI  - Involvement of the medial precentral prefrontal cortex in memory consolidation
      for inhibitory avoidance learning in rats.
AB  - Adult male Wistar rats were trained in a step-down inhibitory avoidance learning
      task (3.0-s, 0.4-mA foot shock), received a 0.5-microl infusion of muscimol
      (0.02, 0.1, or 0.5 microg), AP5 (0.16, 0.34, 0. 5, 1.6, or 5.0 microg), SCH 23390
      (0.05, 0.34, 0.5, or 1.75 microg), saline, or vehicle (DMSO 20%) into the
      anterior medial precentral area (Fr2) (CI) immediately after training, and were
      tested 24 h later. Muscimol (0.02, 0.1, or 0.5 microg), AP5 (0.34 or 0.5 microg),
      or SCH (0.5 or 1.75 microg) were amnesic. Then, animals were infused with
      muscimol (0.1 or 0.5 microg), AP5 (0.34, 0.5, or 5.0 microg), or SCH (0.5 microg)
      at other posttraining times and/or into the junction of Fr1-Fr2 (CII). Muscimol
      (0.1 and 0.5 microg) or SCH into CI were amnesic when given 90 or 180 min after
      training, but not when given 270 min after training. Muscimol (0.5 microg, but
      not 0.1 microg) or SCH into CII were amnesic when given 90 min after training,
      but not when given 0 or 180 min after training. AP5 (0.5, but not 5.0 microg) was
      amnesic when given into CI, but not into CII, at 0 or 180 min posttraining, and a
      trend toward an amnesic effect was seen at 90 min posttraining. The results
      suggest that 1) the glutamatergic, GABAergic, and dopaminergic systems in Fr2 are
      involved in the consolidation of memory for inhibitory avoidance learning, either
      directly or as parts of modulatory systems; and 2) timing of involvement of
      anterior Fr2 (CI) is different from that of posterior Fr2 (CII).

PMID- 10899380
TI  - Nitric oxide modulation affects the tissue distribution and toxicity of
      bupivacaine.
AB  - We have previously demonstrated that inhibition of nitric oxide synthase (NOS)
      alters the toxicity of local anesthetics including bupivacaine. Because
      significant changes in blood distribution are associated with the use of
      nonselective NOS inhibitors, the purpose of this study was to determine whether
      modification of bupivacaine toxicity by nonselective NOS inhibition is due to
      alteration in tissue disposition of bupivacaine. Rats were anesthetized with
      halothane and pretreated with either: 1) a nonselective NOS inhibitor, N(omega)
      nitro-L-arginine methyl ester (L-NAME, 2 mg/kg/min, IV for 30 min); 2) a neuronal
      NOS inhibitor, 7-nitroindazole (7-NI, 30 mg/kg, IP); or 3) vehicle (control).
      Thirty minutes later, bupivacaine 2 mg/kg/min IV was infused until onset of
      seizures, arrhythmias, or asystole. L-NAME caused a rapid increase in plasma
      bupivacaine concentrations (3-4 times faster than in the other groups), which was
      associated with markedly lower bupivacaine doses (mg/kg) required to produce
      arrhythmias in L-NAME (4.2 +/- 0.5) vs. control (26 +/- 3, p < 0.01) and 7-NI
      groups (17 +/- 3, p < 0.01). Myocardial bupivacaine concentrations at arrhythmia
      onset were slightly lower in the L-NAME group. Bupivacaine seizure doses in 7-NI
      and L-NAME pretreated animals were similar to control but significantly different
      from each other. Brain bupivacaine concentrations at seizure onset were similar
      among the groups. There were no significant differences between 7-NI and control
      groups in any parameter observed. We conclude that enhanced cardiotoxicity of
      bupivacaine by nonselective NOS inhibition is primarily due to rapid increases in
      plasma and myocardial distribution of bupivacaine.

PMID- 10899381
TI  - Non reciprocal cross-sensitization between cocaine and BTCP on locomotor activity
      in the rat.
AB  - Measurement of locomotor sensitization was employed to characterize the effect of
      intermittent treatment with N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine
      (BTCP) and cocaine in the rat. Like cocaine, BTCP possesses high affinity for the
      dopamine transporter and inhibits dopamine reuptake. Although both drugs exhibit
      similar behavioral and neurochemical profiles with acute administration, there is
      tentative evidence to suggest that following chronic treatment BTCP does not
      induce neurochemical sensitization, and can attenuate cocaine-induced
      neurochemical sensitization in the striatum. Male Wistar rats were randomly
      divided into five groups after determining baseline locomotor activity. Three
      groups were treated with either saline (saline/saline), cocaine (20 mg/kg;
      cocaine/cocaine), or BTCP (10 mg/kg; BTCP/BTCP) for 10 days. The remaining two
      groups were treated with cocaine (20 mg/kg) or BTCP (10 mg/kg) for 3 days,
      followed by administration of BTCP (10 mg/kg; cocaine/BTCP) or cocaine (20 mg/kg;
      BTCP/cocaine) for 7 days. Locomotor sensitization was observed in all groups.
      However, although cross-sensitization on the day of substitution (day 4) was
      found in the BTCP/cocaine group, cross-sensitization was not observed in the
      cocaine/BTCP group. These results suggest that although the locomotor-activating
      effects of BTCP and cocaine are similar, the two drugs do not act identically,
      and different neural mechanisms may underlie BTCP and cocaineinduced
      sensitization.

PMID- 10899382
TI  - Mecamylamine blockade of both positive and negative effects of IV nicotine in
      human volunteers.
AB  - The ganglionic blocker mecamylamine blocks the positive reinforcing effects of IV
      nicotine, but has been shown to increase cigarette smoking behavior under some
      conditions. The effects of mecamylamine on subjective and physiologic responses
      to IV nicotine were evaluated in seven healthy male volunteer cigarette smokers
      who provided informed consent and resided on a clinical pharmacology research
      unit. On four separate days, each subject was given a different oral dose of
      mecamylamine (placebo, 5, 10, or 20 mg). One hour later subjects received the
      first of four doses of IV nicotine (placebo, 0.75, 1.5, and 3.0 mg); the
      remaining injections were given at 1-h intervals. Both the positive effects
      following 0.75 mg and negative effects following 3.0 mg of nicotine were
      significantly reversed by mecamylamine. Thus, the mecamylamine-induced increase
      in smoking may be due both to competitive blockade of nicotinic receptors and
      nicotine's reversal of aversive effects.

PMID- 10899383
TI  - Effects of buspirone, diazepam, and zolpidem on open field behavior, and brain
      [3H]muscimol binding after buspirone pretreatment.
AB  - The effects of 5-HT(1A) receptor agonist buspirone, a nonselective (diazepam),
      and a selective (zolpidem) GABA(A) receptor agonist were compared in the open
      field test of neophobia. Unhabituated rats were pretreated with the drugs once,
      prior to a first exposure to the open field, and their behavior was recorded both
      during this test and during a second trial 24 h later. It has been hypothesized
      that the decrease in exploratory activity observed during the second test session
      may be considered an adaptive reaction to the first day aversive experience
      (neophobia). If so, a selective modulation of 5-HT and GABA systems activity
      during the test could bring about significant changes in animal behavior on the
      retest. Buspirone at the lowest dose of 0.3 mg/kg revealed anxiolytic-like
      properties on the first day, whereas the action of diazepam and zolpidem was
      modulated by the dose-related sedative effect. At the dose of 2.4 mg/kg buspirone
      elicited delayed in time anxiolytic-like action, i.e., produced the
      antithigmotactic effect during the retrial 24 h later. Diazepam and zolpidem
      failed to exhibit similar profile of action. Autoradiography of [3H]muscimol
      binding after pretreatment of rats with buspirone showed a significant increase
      in the selective radioligand binding within the frontal cortex and a similar,
      near-significant tendency in the dentate gyrus of the hippocampus. The behavioral
      data validate buspirone as important drug for the treatment of anxiety disorders,
      devoid of disruptive influence on motor and cognitive processes. The open field
      test, as modified by us, appeared sensitive in distinguishing the behavioral
      profiles of action of different anxiolytic compounds, including 5-HT(1A) receptor
      agonist. The present results support the assumption that reduced turnover of 5-HT
      due to stimulation of 5-HT(1A) autoreceptors, may bring about changes in GABA(A)
      receptor system activity, in some brain structures, leading to the anxiolytic
      effect.

PMID- 10899384
TI  - Modulation of morphine-induced antinociception by palatable solutions in male and
      female rats.
AB  - The analgesic potency of opioid drugs varies as a function of gender, and can be
      modified by the intake of palatable sweet-tasting solutions. To determine if
      gender interacts with diet-induced changes in antinociceptive responses, male and
      female Long-Evans rats were fed laboratory chow and water alone, or chow, water
      and either a 32% w/v sucrose solution or a 0.15% w/v saccharin solution, and
      tested in two analgesic paradigms, the tail-flick test and the hot-plate test.
      For both tests, antinociceptive responses of male and female rats were tested
      following administration of cumulative doses (1.25, 2.5, 5.0, and 10.0 mg/kg, SC)
      of morphine sulfate. On the tail-flick test, morphine produced dose-related
      increases in antinociceptive responses. In addition, relative to both the chow
      only and saccharin conditions, chronic intake of the sucrose solution access
      significantly augmented morphine's antinociceptive properties. On the hot-plate
      test, when the plate was heated to 51 degrees C, morphine led to significant dose
      related increases in antinociceptive responses, but diet did not affected
      antinociceptive responses. When the temperature of the hot plate was increased to
      53 degrees C, there was a trend for animals given sucrose to have greater
      antinociceptive responses than those given either chow alone or saccharin. No
      differences in baseline pain sensitivity or morphine-induced analgesia were
      observed as a function of gender.

PMID- 10899385
TI  - Suppressive effects of vietnamese ginseng saponin and its major component
      majonoside-R2 on psychological stress-induced enhancement of lipid peroxidation
      in the mouse brain.
AB  - We investigated the in vivo effects of Vietnamese ginseng saponin (VG saponin)
      and its major component majonoside-R2 (MR2) on psychological stress-induced
      enhancement of lipid peroxidation in the mouse brain. Psychological stress
      exposure using a communication box system for 4 h significantly increased the
      content of thiobarbituric acid reactive substance (TBARS), an index of lipid
      peroxidation activity, in the brain. Pretreatment with VG saponin (15-25 mg/kg,
      PO) and MR2 (1-10 mg/kg, IP) significantly attenuated the psychological stress
      induced increase in TBARS content in the brain. The aglycone of MR2 (MR2
      aglycone: 1.2 mg/kg, IP), at the equivalent dose of MR2 (i.e., 3 mg/kg, IP), also
      produced the suppressive effect on the increase in the TBARS content. The in vivo
      suppressive effect of MR2 was dose dependently attenuated by flumazenil (3 and 10
      mg/kg, IP), a benzodiazepine receptor antagonist, and pregnenolone sulfate (10
      mg/kg, IP), a neurosteroidal negative allosteric modulator of GABA(A) receptors.
      These findings suggest that VG saponin and its major component MR2 have
      preventive effects on the psychological stress-induced brain cell membrane
      damage, and that the effect of MR2 is partly due to enhancement of GABA(A)-ergic
      systems in the brain.

PMID- 10899387
TI  - Fluorescence ratio intrinsic basis states analysis: a novel approach to monitor
      and analyze protein unfolding by fluorescence.
AB  - Fluorescence ratio intrinsic basis states analysis (FRIBSTA) is a novel method
      allowing quantitative estimation of the stability of proteins in aqueous solution
      as a function of temperature. In FRIBSTA emission fluorescence spectra are
      repeatedly recorded while ramping temperature from < or =-15 to > or =100 degrees
      C. Subsets of these are identified as reference spectra of the protein in either
      its folded or in its heat denatured configuration. Each reference spectrum of
      both sets is normalized by its own integrated fluorescence intensity to give a
      fractional area spectrum. Linear extrapolations of these normalized reference
      spectral shapes over the entire temperature range of measurement are then used to
      deconvolute each experimental emission spectrum to give a fraction of emission
      from native state and a fraction from denatured state. Additionally, the
      integrated emission fluorescence intensity for the native configuration is fitted
      and extrapolated over the temperature range of measurement. Division of the
      deconvoluted native integrated fluorescence intensity by the fitted-extrapolated
      integrated emission fluorescence intensity yields the fraction folded. The free
      energy functions derived from fraction unfolded are presented for beta
      lactoglobulin and phosphoglycerate kinase. According to these results both
      proteins are considerably less stable than heretofore assumed at ambient
      temperatures and partially denatured at temperatures < or =0 degrees C. The
      method is employed to study the effect of denaturants on these proteins as well.
      The major usefulness of FRIBSTA is that one can directly measure the protein
      stability at ambient and subambient temperatures in the absence of denaturants
      rather than predicting it by extrapolation from heat denaturation data.

PMID- 10899386
TI  - Manipulation of central GABAergic and dopaminergic systems alters stress
      responding in the rat.
AB  - Activation of central GABA(A) systems with muscimol has been shown to facilitate
      stress responding and GABA is known to modulate central dopaminergic activity. To
      evaluate the possibility that this effect of muscimol may depend upon a dopamine
      mechanism we have tested the effect of intracerebroventricular coadministration
      of muscimol and the selective D(1) antagonist SCH 23390 on behaviors evoked by
      tail pinch stress. When injected by themselves muscimol (1.75 nmol) facilitated
      stress-evoked oral behavior while SCH 23390 (6-600 nmol) produced a dose-related
      suppression of oral behavior. Coadministration of muscimol and doses of SCH 23390
      selected for producing no (6 and 30 nmol), or marginal (60 nmol), effects on
      stress responding resulted in a dose-related reversal of the increase in orality
      seen with muscimol alone. The results are consistent with the notion that
      stressful stimuli activate central GABA(A) systems which, in turn, enhance
      dopaminergic neurotransmission.

PMID- 10899388
TI  - Adsorption of polyvalent cations to bilayer membranes from negatively charged
      lipid: estimating the lipid accessibility in the case of complete binding.
AB  - The effect of trivalent (Gd(3+) and Yb(3+)) and divalent (Be(2+) and Ca(2+))
      cations on suspensions of multilamellar liposomes formed from brain PS and DMPS
      has been studied using microelectrophoresis and DSC techniques, respectively. The
      zeta potential values have been shown to strongly depend on the total lipid
      concentration in the suspension. At moderate concentrations of the polyvalent
      cations, the total cation concentration exceeds the bulk one several times due to
      adsorption of cations to the liposomes. A modification of the Gouy-Chapman-Stern
      theory in the case of unknown bulk concentration of the polyvalent cation is
      presented. An intrinsic association constant for Be(2+) ions was evaluated to be
      about K(2) approximately 50 M(-1). The algorithm for estimating the
      concentrations of the accessible (to exogenously added polyvalent cations) lipid
      binding sites is described. These values are consistent with the subsurface
      concentrations of the polyvalent cations, which monotonously increase with the
      total concentration of the polyvalent cations. The calculated lipid
      accessibilities are shown to be in accordance with the DSC data.

PMID- 10899389
TI  - Bacterial bioluminescent emission from recombinant Escherichia coli harboring a
      recA::luxCDABE fusion.
AB  - This paper describes the quantitative evaluation of a bioluminescence assay for
      DNA damaging agents with respect to the linearity, sensitivity, specificity and
      dependence on the cell culture status. A recombinant bacterium, DPD2794,
      harboring a plasmid with a recA promoter fused to the luxCDABE operon, showed a
      very sensitive response to DNA-damaging stress. DPD2794 was found to show no
      noticeable response to non-mutagenic agents, i.e. phenol, except for some false
      responses appearing soon after injection. DPD2794 also showed a highly sensitive
      response to Mitomycin C, which was found to be a growth-stage-dependent response,
      not a growth-rate-dependent response. In addition, the relationship between the
      bioluminescence emitted in vivo, luciferase activity measured in vitro, and the
      amount of Lux proteins expressed was determined. The intensity of the
      bioluminescence emitted was found to be proportional to the luciferase activity
      in vitro, while the bioluminescence also seems to be correlated with the level of
      Lux proteins expressed in these Escherichia coli cells, up to 230 min post
      induction.

PMID- 10899390
TI  - Assay for Laccase activity by microcalorimetry: laccase was extracted from china
      lacquer of Rhus vernicifera.
AB  - The reactions between Laccase (extracted from China lacquer of Rhus vernicifera)
      and various substrates (3,4-Dihydroxybenzaldehyde, Guaiacol, Pyrogallol, Gallic
      acid) have been studied using LKB-2107 batch microcalorimetry system. Based on
      calorimetry, a new method has been proposed. Laccase activity and the Michaelis
      constant K(m) have been determined simultaneously by this method. The method is
      simple, sample-saving, and valid for a wider range of substrate concentrations.
      Furthermore, it can be extended for assaying other enzymes catalyzing reactions
      using this method.

PMID- 10899391
TI  - Using a neural network for lane-tracking of DNA sequencing slab gels.
AB  - High quality lane-tracking of gel images is the first task, and thus a
      prerequisite, for successful trace processing and base-calling of DNA sequencing
      slab gels. In most approaches, it is based on statistical calculations, for
      instance variance and co-variance analysis between neighboring pixel columns in
      the image. On the basis of these statistical calculations, Kohonen's self
      organization neural network model was introduced. We have found that, using
      several well-structured input data, Kohonen's self-organization neural network
      model can be trained to fulfill our task of lane-tracking. Furthermore, the
      quality of lane-tracking could be improved compared to algorithmic approaches.

PMID- 10899392
TI  - Simple and rapid method for the determination of coproporphyrinogen oxidase
      activity.
AB  - Coproporphyrinogen oxidase, the sixth enzyme in the biosynthetic heme pathway,
      catalyzes the oxidative decarboxylation of coproporphyrinogen III to
      protoporphyrinogen IX. A reversed-phase high pressure liquid chromatography
      method was developed to measure coproporphyrinogen oxidase enzymatic activity in
      rat liver. With this method, the separation, identification and quantification of
      coproporphyrin III (oxidized substrate) and protoporphyrin IX (oxidized product)
      present in the assays could be carried out with no need of derivatization and in
      less than 15 min. Rat and human liver coproporphyrinogen oxidase basal activities
      determined using this method were 0.41+/-0.05 nmol of protoporphyrin IX/h per mg
      of hepatic protein and 0.87+/-0.06 protoporphyrin IX/h per mg of hepatic protein,
      respectively. Kinetic studies showed that optimum pH for rat CPGox is 7.3, and
      that its activity is linear in the range of protein concentrations and incubation
      times assayed. The present paper describes a sensitive, specific and rapid
      fluorometric high performance liquid chromatography method to measure
      coproporphyrinogen oxidase, which could be applied to the diagnosis of human
      coproporphyria, and which is also suitable for the study of lead and other metal
      poisoning that produce alterations in this enzymatic activity.

PMID- 10899393
TI  - A chromatographic study of the reaction sequence and effect of ligand on the
      reaction of human hemoglobin with negatively charged isothiocyanates:
      characterization of an intermediate modified only on the amino termini of the
      alpha chains.
AB  - A HPLC investigation of the reaction of 4-isothiocyanatobenzoic acid and 4
      isothiocyanatobenzenesulfonic acid with oxy- and deoxyhemoglobin was carried out.
      The initial reaction of aromatic isothiocyanato sulfonates and benzoates with
      either oxy- or deoxyhemoglobin is with the amino termini of the alpha chains
      followed by a much slower reaction with the amino termini of the beta chains.
      Both reactions are much faster with deoxyhemoglobin than with oxyhemoglobin. An
      intermediate reacted only at the termini of the alpha chains with 4
      isothiocyanatobenzoic acid was isolated and purified and its functional
      properties determined. The intermediate showed a reduced oxygen affinity over a
      wide pH range and a reduced alkaline Bohr effect in the absence of chloride. The
      oxygen affinity of the intermediate showed a reduced but still significant
      response to chloride.

PMID- 10899394
TI  - Expression of fos-related antigen-2 in rat hippocampus after middle cerebral
      arterial occlusion.
AB  - AP-1 transcription factors have been shown to be induced in the brain after
      ischemic injury. However, their roles in neuronal survival or death have yet to
      be defined. Here, we report the discovery of elevated nuclear levels of fos
      related antigen-2 (FRA-2) in the nuclei of hippocampal neurons seven days after
      middle cerebral artery occlusion (MCAO). Expression of FRA-2 and AP-1 DNA binding
      activity is elevated in hippocampi ipsilateral as well as contralateral to MCAO.
      Using Fluoro-Jade staining as a marker of neurodegeneration, FRA-2 was not found
      to be expressed in degenerating neurons. Thus, FRA-2 is expressed in neurons that
      survive ischemic insult suggesting a role for this transcription factor in
      neuronal adaptation to the post-injury state.

PMID- 10899395
TI  - Cortical interleukin-1 beta elevation after traumatic brain injury in the rat: no
      effect of two selective antagonists on motor recovery.
AB  - Interleukin-1 is an inflammatory cytokine implicated in secondary responses to
      traumatic brain injury. We utilized a specific IL-beta enzyme-linked
      immunoadsorbant assay to examine the expression of IL-beta after lateral fluid
      percussion brain injury in the rat. IL-beta was significantly elevated in the
      ipsilateral injured cortex at 4 h after injury. Increased levels of IL-beta were
      also observed at 12, 24 and 72 h after injury, although such changes did not
      reach statistical significance. To determine whether injury-induced IL-beta
      expression may contribute to subsequent neurological impairment, we treated rats
      with either of two structurally different, selective IL-1 antagonists and
      monitored neurological recovery 1, 7 and 14 days later. Intracerebroventricular
      treatment with either the endogenous interleukin-1 receptor antagonist (10
      microg) at 15 min, 2, 4, 6, and 8 h after injury or soluble IL-1 receptors (10
      microg) at 15 min, 4 and 8 h after injury did not significantly alter outcome in
      a series of motor tasks. These data suggest that cortical elevations of IL-beta
      follow traumatic brain injury, but they may not contribute to subsequent
      neurological impairment.

PMID- 10899396
TI  - Spectro-temporal receptive fields of midbrain auditory neurons in the rat
      obtained with frequency modulated stimulation.
AB  - Single unit responses at the auditory midbrain of the anesthetized rat were
      characterized in terms of spectro-temporal receptive field (STRF) using random
      frequency modulated (FM) tones and peri-spike averaging. STRFs were obtained from
      121 FM-sensitive units covering a wide range of characteristic frequency (CF).
      Roughly half of the neurons showed clearly preferred stimulus time profiles that
      formed either a single, double or multiple bands. Neurons with a single-band STRF
      appeared to be sorted into positive or negative directional sensitivity for FM
      modulation on the basis of their CF either below or above 10 kHz. This
      directional selectivity is discussed in relation to the most sensitive part of
      the rat's audiogram.

PMID- 10899397
TI  - In utero ethanol exposure decreases rapid eye movement sleep in female Sprague
      Dawley rat offspring.
AB  - There is substantial evidence to suggest that ethanol exposure during vulnerable
      periods of prenatal somatic growth results in a number of morphological
      abnormalities and cognitive deficits in offspring. Amongst the characteristics
      exhibited by affected individuals are abnormal sleeping patterns, particularly
      abnormal rapid eye movement (REM) sleep. To better understand how prenatal
      ethanol exposure specifically affects sleeping patterns in offspring, an animal
      model of fetal alcohol syndrome was investigated using the Sprague-Dawley rat.
      Our study demonstrated that the amount of time spent in REM sleep was reduced in
      female, but not male rats, which were exposed to ethanol in utero as compared to
      male and female saline controls. Similarly, % REM sleep for female saline control
      rats was almost twice that of females exposed to ethanol (11. 9 vs. 6.9%). By
      contrast, ethanol treated and control saline males did not differ on the % REM
      measure (11.5 vs. 10.4%), nor did they differ from the female saline controls. No
      differences were observed between males and females or treatment groups in terms
      of time spent in either slow wave sleep or wakefulness.

PMID- 10899398
TI  - Peripheral chemoreceptor activation enhances 5-hydroxytryptamine release in the
      locus coeruleus of conscious rats.
AB  - Intravenous bolus injection of KCN (40 microg) elicited brief but pronounced
      tachypnea, bradycardia and pressor response, and led to a 37% increase in 5
      hydroxytryptamine (serotonin) (5-HT) release in the locus coeruleus (LC) of
      freely moving rats. Slow infusion of KCN (15 microg/min) for 10 min induced only
      a slight pressor response, but increased the respiration rate (+39 breaths/min),
      as well as 5-HT release in the LC (+60%) throughout the infusion. In rats with
      transected chemoreceptor afferents, neither injection or infusion of KCN changed
      5-HT release, suggesting that in intact animals, the effect on extracellular 5-HT
      was due to activation of peripheral chemoreceptors. In summary, we report that
      peripheral chemoreceptor activation enhances 5-HT release in the LC, indicating
      that 5-HT might be involved in the modulation of LC activity by ascending
      chemosensory information.

PMID- 10899399
TI  - Involvement of sigma 1 receptors in methamphetamine-induced behavioral
      sensitization in rats.
AB  - MS-377 is a novel selective sigma(1) ligand, currently being developed for the
      treatment of schizophrenia. In the present study, we examined the effects of MS
      377 on behavioral sensitization induced by subchronic treatment with
      methamphetamine. MS-377 was administered at doses of 1.875-15 mg/kg (p.o.), to
      rats, and methamphetamine was administered at doses of 2 mg/kg (i.p.), 60 min
      later once daily for 10 days. Repeated administration of methamphetamine caused
      enhanced stereotypy, and behavioral sensitization was developed. MS-377 did not
      affect the acute effects of methamphetamine. However, co-administration of MS-377
      attenuated the development of methamphetamine-induced behavioral sensitization in
      a dose-dependent manner. These results suggested that sigma(1) receptors play an
      important role in the developmental period of behavioral sensitization induced by
      methamphetamine in rats.

PMID- 10899400
TI  - Oxytocin depresses spontaneous gamma-aminobutyric acid-ergic inhibitory
      postsynaptic currents in cultured mitral cells of the rat olfactory bulb by a
      presynaptic mechanism.
AB  - Oxytocin (OT) modulation of synaptic transmission between olfactory bulb neurones
      has been implicated in the induction of maternal behaviour, but the mechanism of
      action is unknown. We examined the action of OT on gamma-aminobutyric acid(A)
      (GABA(A)) receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs)
      in cultured mitral/tufted (M/T) cells with the use of whole-cell patch-clamp
      recordings. OT reversibly reduced the frequency of sIPSCs without affecting the
      amplitudes. The effect of OT on sIPSCs was mimicked by the OT receptor agonist
      [Thr(4), Gly(7)]-OT in a reversible manner and blocked by the OT receptor
      antagonist desGly-NH(2)(9), d(CH(2))(5)-[Tyr(Me)(2), Thr(4)]-ornithine-vasotocin.
      OT has no effect, however, on the membrane currents evoked by exogenous
      application of GABA. These results demonstrate that OT depresses GABA(A) receptor
      mediated sIPSCs in M/T cells by a presynaptic mechanism.

PMID- 10899401
TI  - Alpha-synuclein immunoreactivity of huntingtin polyglutamine aggregates in
      striatum and cortex of Huntington's disease patients and transgenic mouse models.
AB  - Polyglutamine expansions in proteins are implicated in at least eight inherited
      neurodegenerative disorders, including Huntington's disease. These mutant
      proteins can form aggregates within the nucleus and processes of neurons possibly
      due to misfolding of the proteins. Polyglutamine aggregates are ubiquitinated and
      sequester molecular chaperone proteins and proteasome components. To investigate
      other protein components of polyglutamine aggregates, cerebral cortex and striata
      from patients with Huntington's disease and full-length cDNA transgenic mouse
      models for this disease were examined immunohistochemically for alpha-synuclein
      reactivity. Our findings demonstrate that alpha-synuclein can be used as a marker
      for huntingtin polyglutamine aggregates in both human and mice. Moreover in the
      HD transgenic mice, the intensity of immunoreactivity increases with age. The
      significance of recruitment of alpha-synuclein into huntingtin aggregates and its
      translocation away from the synapses remains to be determined. We propose that
      aberrant interaction of mutant huntingtin with other proteins, including alpha
      synuclein, may influence disease progression.

PMID- 10899402
TI  - Non-invasive magnetoneurography for 3D-monitoring of human compound action
      current propagation in deep brachial plexus.
AB  - Compound action current (CAC) propagation along nerve fibers running deep in the
      human brachial plexus was 3D-visualized based on non-invasive 49-channel
      superconducting quantum interference device (SQUID) magnetoneurography. Spatio
      temporal mappings over the upper thoracal quadrant of magnetic fields (<100 fT)
      evoked upon alternating median and ulnar nerve stimulation in seven healthy
      volunteers showed consistently smoothly propagating dipolar patterns for both the
      CAC depolarization and repolarization phases. Multipolar current source
      reconstructions (i) distinguished spatially CAC propagation pathways along either
      median or ulnar plexus fibers, allowed (ii) to calculate local conduction
      velocities ( approximately 56 m/s) and (iii) even to estimate the CAC extension
      along the nerve fibers (depolarization phase: approximately 11 cm). Thus, for
      deep proximal nerve segments magnetoneurography can provide a detailed tracing of
      neural activity which is a prerequisite to localize non-invasively focal nerve
      malfunctions.

PMID- 10899403
TI  - Glutamate is the fast excitatory neurotransmitter of small cardioactive peptide
      containing Aplysia radula mechanoafferent neuron B21.
AB  - B21 is a radula mechanoafferent neuron in the mollusc Aplysia which likely plays
      a crucial role in integrating environmental cues into the feeding motor program.
      To facilitate understanding B21's interactions with its postsynaptic followers,
      we sought to identify its neurotransmitter. We find that B21 makes a chemical
      synapse onto the follower neuron B8. Although B21-induced excitatory postsynaptic
      potentials (EPSPs) in B8 paradoxically diminish in amplitude with B8
      hyperpolarization, we show that an inwardly rectifying current is responsible. We
      conclude that these B21-induced EPSPs are likely glutamatergic as they are
      blocked by the glutamate antagonist DNQX. Furthermore, B8 exhibits a depolarizing
      response to exogenous glutamate, which is antagonized by DNQX. Finally, exogenous
      glutamate occludes B21-evoked EPSPs in B8.

PMID- 10899404
TI  - Increased expression of p53 and Bax in the spinal cords of rats with experimental
      autoimmune encephalomyelitis.
AB  - The expression of pro-apoptotic molecules p53 and Bax in the spinal cord of rats
      with experimental autoimmune encephalomyelitis (EAE) was examined. Apoptosis was
      confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL) method. TUNEL (+) apoptotic cells were mainly either ED1 (+)
      macrophages or T-cells in the parenchyma of EAE. Western blot analysis showed
      that both p53 and Bax expression significantly (P<0. 01) increased in the spinal
      cords of EAE rats at the peak stage, and thereafter declined. An
      immunohistochemical study showed that inflammatory cells (notably T cells) in the
      parenchyma express p53 and Bax, while brain cells, including neurons and glia,
      were devoid of nuclear staining for these molecules. The nuclear expression of
      p53 largely matches apoptotic cells in the parenchyma of EAE. These findings
      suggest that the pro-apoptotic molecules p53 and Bax may play an important role
      in eliminating T cells in the parenchyma in EAE.

PMID- 10899405
TI  - Mediators of neuronal activation in the rat brainstem following intestinal
      anaphylaxis.
AB  - Brainstem neurones become activated following intestinal antigen challenge but
      the signalling mechanisms have not been resolved. Our aim was to determine the
      extent of brainstem activation after intestinal anaphylaxis induced by chicken
      egg albumin (EA). An increase in Fos-positive neurones in the nucleus tractus
      solitarius (nTS) was observed following EA (P<0.05). Fos-expression was decreased
      following pretreatment with pyrilamine and ondansetron i.p. and to a similar
      extent when both antagonists were administered together (all P<0.05 vs. control).
      Indomethacin had no effect on Fos-expression after antigen challenge. 5-HT and
      histamine but not prostanoids, released following intestinal anaphylaxis, induce
      nTS activation via histamine H(1)- and 5-HT(3) receptors. Information on the
      intestinal inflammatory status is relayed centrally and may play a role in
      reflexes and behavioural responses to activation of the immune system.

PMID- 10899406
TI  - The novel non-competitive N-methyl-D-aspartate antagonist gacyclidine blocks the
      glutamate-induced release of hydroxyl radicals in the striatum under conditions
      in which dizocilpine does not. A microdialysis study in rats.
AB  - Gacyclidine, a new neuroprotectant aimed to non-competitively antagonize N-methyl
      D-aspartate (NMDA) receptors, and dizocilpine blocked the hydroxyl radical
      response to toxic amounts of glutamate, perfused through a microdialysis
      implanted in the striatum of conscious rats. Furthermore, the hydroxyl radical
      response resulting from the infusion of lower doses of glutamate, which could not
      be inhibited by the same amounts of dizocilpine nor by acute alcohol exposure,
      still remained sensitive to gacyclidine inhibition. Thus, oxidative stress
      resulting from a glutamate discharge involves the activation of both NMDA
      receptors, and of non-NMDA mechanism(s) which, with moderate glutamate levels,
      were still antagonized by gacyclidine. Enhanced blockage of toxic hydroxyl
      radicals might explain the different and possibly higher neuroprotective property
      of gacyclidine as compared with other non-competitive NMDA antagonists.

PMID- 10899407
TI  - Protective effect of microglial conditioning medium on neuronal damage induced by
      glutamate.
AB  - To examine the effect of microglial conditioning medium (MCM) on damaged neurons,
      cultured neurons exposed to glutamate were incubated with MCM. More neurons
      survived in these groups, particularly in the case of glutamate stimulation of
      microglia. Therefore cultured neurons exposed to glutamate were incubated with
      MCM at predetermined intervals after glutamate stimulation. Neuronal cultures
      using MCM at 1, 2 and 6 h after glutamate stimulation had more surviving cells
      than those using unstimulated MCM. Neuronal cultures using MCM at 12 and 24 h had
      as much surviving cells as those using unstimulated MCM. These results indicate
      that the neuroprotective effect of microglia appears only in the early phase
      after treatment of glutamate and disappears in the late phase.

PMID- 10899408
TI  - Zolmitriptan reverses blink reflex changes induced during the migraine attack in
      humans.
AB  - The question about the 5-hydroxytryptamine (5-HT)(1B-1D) receptors agonists, if
      the clinical efficacy in migraine attacks is linked with the action at the
      central level or at the peripheral one, is still unresolved. We evaluated the
      effects of zolmitriptan and sumatriptan on blink reflex in thirty migraine
      without aura patients during the attacks in order to assess the central action on
      the trigeminal system. Both drugs were effective in reducing headache severity
      compared to placebo. In the migraine attack an increased area of the R3 component
      on the pain side was observed; it was suppressed by zolmitriptan, which confirmed
      its action on the central trigeminal circuits, though the clinical relevance of
      this effect could be questioned.

PMID- 10899409
TI  - The genetic association between Cathepsin D and Alzheimer's disease.
AB  - The aspartyl protease Cathepsin D has previously been suggested to play a role in
      the Alzheimer's disease (AD) process because of its ability to cleave the beta
      amyloid precursor protein and the possibility that it may be one of the
      'secretase' enzymes. A functional C-->T polymorphism in the Cathepsin D gene
      (CATD) has been reported to be associated with increased risk for AD in Caucasian
      case-control studies; specifically, the T-carrying genotypes confer increased
      risk. We have examined this association in our own Caucasian dataset of 210 AD
      cases and 120 controls, and in an additional Hispanic dataset comprising 79 AD
      cases and 112 controls. In Hispanics we find a modest interaction between CATD
      genotype and age of onset on risk for AD, such that the non-T-carrying genotype
      confers increased risk. In our Caucasian dataset we find no evidence for
      association between the CATD polymorphism and AD, although we do observe a small
      tendency towards an increase in the T-carrying genotypes in the case group,
      consistent with previous studies. We conducted an aggregate analysis of the
      published Caucasian datasets and found evidence that this CATD polymorphism (or
      another locus in linkage disequilibrium) does contribute significant, but small
      (<2%) risk for AD.

PMID- 10899410
TI  - A new mutation in the parkin gene in a patient with atypical autosomal recessive
      juvenile parkinsonism.
AB  - We have investigated the presence of mutations in the parkin gene in patients
      with early-onset parkinsonism. Direct sequencing of the polymerase chain reaction
      (PCR) products showed a homozygous G deletion in the exon 7 (c.871delG) in one
      patient. This was a 38-year-old Moroccan woman with a history of parkinsonism of
      18 years of duration. The disease appeared as an apparently sporadic case and was
      characterized by dystonia of the legs at onset and a rapid progression to severe
      generalized parkinsonism but with an excellent maintained response to dopamine
      agonists treatment. The deletion was a frameshift mutation resulting in a stop
      codon at position 297 which causes truncation of the parkin protein. Mutations in
      the parkin gene can be encountered in patients with an apparently sporadic early
      onset parkinsonism, rapidly progressive course and marked and maintained response
      to dopamine agonists.

PMID- 10899411
TI  - Changes in electrophysiological properties of axon terminals of locus coeruleus
      neurons with age in F344 rat.
AB  - Age-dependent changes in electrophysiological properties of locus coeruleus (LC)
      neurons were studied in urethane anesthetized male F344 rats aged 8, 17 and 22
      months. These properties, such as spontaneous firing rate, conduction time, and
      threshold currents were measured for individual LC neurons antidromically
      activated from terminals in the frontal cortex. We found no change in the
      electrophysiological properties with age except for an increased number of low
      threshold LC neurons in 22-month-old rats compared to that of 8-month-old rats.
      These results suggested that the electrophysiological properties of cortical axon
      terminals of LC neurons changed with age.

PMID- 10899412
TI  - Detection of extracellular signal-regulated kinase1/2 in the inner ear of guinea
      pigs.
AB  - Growth factors, such as vascular endothelial growth factor (VEGF) and
      neurotrophins, recently identified in the inner ear of guinea pigs, exert their
      proliferative properties partly through activation of mitogen-activated protein
      kinase/extracellular signal-regulated kinase (MAPK/ERK1/2). In order to
      demonstrate presence of ERK1/2 in the inner ear we performed immunohistochemical
      analysis using specific antibodies to inactive and activated ERK1/2 on paraffin
      sections of temporal bones from guinea pigs (n=5). In the cochlea clear
      immunoreactivity to inactive ERK1/2 was predominant in the spiral ligament, in
      the organ of Corti (intensive staining in supporting cells, faint staining in
      sensory cells) and limbus epithelium, while spiral ganglion cells and nerve
      fibres revealed weak staining. Activated ERK1/2 could be detected sparely in the
      spiral ligament exclusively. In the vestibule inactive ERK1/2 was located in the
      sensory epithelium, in nerve fibres and in vascular endothelium, while activated
      ERK1/2 could be detected in few nerve fibres and synaptic endings (buttons and
      calyces) on hair cells of the maculae and crests and in the endothelium of few
      blood vessels. These findings provide evidence that activated ERK1/2, as a
      general downstream signal of growth factors, may be contributed in the inner ear
      physiology.

PMID- 10899413
TI  - [3H]dihydroalprenolol binding to beta adrenergic receptors in multiple sclerosis
      brain.
AB  - By using immunocytochemistry we previously reported the absence of beta(2)
      adrenergic receptors on astrocytes in multiple sclerosis (MS) white matter. Here,
      we measured beta(1) and beta(2) adrenergic receptor concentrations in postmortem
      brain sections of six MS patients and six controls by using quantitative
      autoradiography with [(3)H]dihydroalprenolol. White matter contained no beta(1)
      adrenergic receptors. In white matter of controls low levels of beta(2)
      adrenergic receptors were detected. In agreement with the immunohistochemical
      study, we were unable to detect beta(2) adrenergic receptors in both normal
      appearing white matter and astrogliotic plaques in MS. Concentrations of beta(1)
      and beta(2) adrenergic receptors in cerebral cortex were not different between
      controls and MS patients.

PMID- 10899414
TI  - Correlation between mammographic manifestations and averaged histopathologic
      nuclear grade using prognosis-predict scoring system for the prognosis of ductal
      carcinoma in situ.
AB  - This retrospective study correlated the mammographic manifestations and averaged
      nuclear grades using Holland, Van-Nuys, and Lagios classifications in 37 cases of
      ductal carcinoma in situ (DCIS); microcalcifications alone were seen in 59.4%,
      microcalcifications with associated mass in 19%, and mass alone in 21.6%. DCIS is
      more likely to be accompanied by microcalcifications than mass on mammography.
      Correlation is good between the nuclear grades of DCIS and mammographic
      manifestations.

PMID- 10899415
TI  - Stereotactic biopsy of noncalcified breast lesions: utility of vacuum-assisted
      technique compared to multipass automated gun technique.
AB  - The purpose of this study was to evaluate the stereotactic 14-gauge, vacuum
      assisted biopsy technique in diagnosing noncalcified breast lesions. Stereotactic
      biopsy of 116 noncalcified breast lesions was performed with either 14-gauge,
      vacuum-assisted technique or multipass, automated large-core technique. The
      number of core samples and time required for each biopsy were compared. Outcome
      for each technique was compared based on recommendations after the mammographic
      histologic review process. Results from surgical excision and mammographic follow
      up were reviewed. The vacuum-assisted technique obtained more tissue cores per
      lesion than the automated gun technique, showed marginal decrease in number of
      repeat biopsies for discordant results, and required fewer short-term follow-up
      mammograms, although the difference did not achieve statistical significance. The
      vacuum-assisted technique can be used successfully to sample noncalcified breast
      masses, with marginal improvement over the automated gun technique.

PMID- 10899416
TI  - Angiolipoma of the breast with microcalcification. Mammographic, sonographic, and
      histologic appearances.
AB  - Angiolipoma of the breast is a rare benign fatty tumor that can be
      mammographically confused with breast carcinoma. We herein report such a case
      presenting as a partial obscured mass with microcalcification on mammogram.
      Sonogram revealed an encapsulated hyperechoic nodule with homogeneous internal
      echo. Microscopic evaluation revealed abundant adipose tissues with evidence of
      proliferating vessels and intravascular hyaline thrombi. To our knowledge,
      angiolipomas of the breast containing microcalcification secondary to
      intravascular thrombi had not been previously reported.

PMID- 10899417
TI  - Central nervous system atypical teratoid/rhabdoid tumour of infancy. CT and mr
      findings.
AB  - In 1995, as a result of the observation of Rhabdoid elements among the other
      components of a Teratoid/Rhabdoid tumor (TRT), a new nomenclature was introduced,
      Atypical Teratoid/Rhabdoid Tumor (ATRT) of infancy and childhood. We report the
      clinical history and radiological findings in a child affected by central nervous
      system (CNS) ATRT.

PMID- 10899418
TI  - Massive hemoptysis due to Mycobacterium fortuitum infection controlled with
      bronchial artery embolization - a case report.
AB  - We reported a case of first reported pulmonary infection due to Mycobacterium
      fortuitum (M. fortuitum) with massive hemoptysis, successfully treated by
      bronchial artery embolization (BAE). A 78-year-old male was admitted to our
      hospital complaining of massive hemoptysis. A biochemical examination and DNA/DNA
      hybridization revealed M. fortuitum in the culture of his sputum. He was treated
      by BAE, and antituberculous agents and levofloxacin. The patient remains well
      without recurrence more than one and a half years after the admission.

PMID- 10899419
TI  - Case report: the "yin-yang" sign-seen with spiral computed tomography for
      pulmonary embolus.
AB  - The diagnostic evaluation of pulmonary embolism has recently been modified to
      include contrast-enchanced spiral computed tomography of the chest. CT has found
      acceptance as not only an imaging modality for diagnosing pulmonary embolus, but
      is also useful in depicting alternate diagnoses to explain acute shortness of
      breath. This article describes a unique pattern of contrast enhancement observed
      during a routine spiral contrast-enhanced CT to evaluate suspected pulmonary
      embolism. The appearance has been named the "yin-yang" sign due to the
      alternating areas of contrast enhancement seen in the cardiac chambers on
      sagittal and coronaly reformatted images. This article describes the appearance
      of the sign and attempts to explain how intravenous contrast assumes this
      configuration with rapid spiral acquisition of images. The importance of
      recognizing this normal variant of contrast enhancement which may appear on
      routine examinations for pulmonary embolus is also discussed.

PMID- 10899420
TI  - Barium enema following incomplete colonoscopy.
AB  - The purpose of this article is to describe our findings on barium enema in
      patients who have had incomplete colonoscopy. For patients undergoing colonoscopy
      and barium enema within 6-months of each other between 1991 and 1997, barium
      enemas were reevaluated for redundant anatomy as well as lesions. Seventy-seven
      women and 30 men underwent 108 barium enemas. The most common finding was a
      redundant colon in 68% (55/81) of study patients, but only 33% (9/27) of control
      (complete colonoscopy) patients.

PMID- 10899421
TI  - Leiomyoma of the extraperitoneal round ligament: CT demonstration.
AB  - We report the computed tomography (CT) description of a leiomyoma involving the
      extraperitional portion of the round ligament. Although unusual, such a lesion
      may mimic other mass lesions in this vicinity including adenopathy,
      endometriomas, and inguinal hernias.

PMID- 10899422
TI  - Evaluation of extrahepatic portal hypertension and surgical portal systemic
      shunts by intravenous CT portography.
AB  - The purpose of this study was to evaluate the splenoportal (SP) axis and patency
      of portal systemic shunts in extrahepatic portal venous obstruction (EHO) by
      intravenous CT portography (CTP). Fifty-five patients of preshunt EHO, and 21
      patients of postshunt (surgical portal systemic shunts) EHO, were subjected to
      intravenous CTP on a subsecond helical CT scanner. Thin, axial sections and three
      dimensional (3-D) reconstructions, including maximum intensity projection (MIP)
      and shaded surface display (SSD), were obtained. The findings were correlated
      with Color Doppler Flow Imaging (CDFI). In the EHO preshunt group, the site of
      the block demonstrated on CTP correlated with CDFI in 53 of 55 cases. In the
      postshunt group, shunt patency evaluation by CTP was in agreement with CDFI in 19
      of 21 patients (8 patent; 13 blocked). Two patients in each group could not be
      evaluated on CDFI, while CTP could provide the appropriate information. There was
      no false positivity or negativity with CTP in patients evaluated on both
      modalities. The etiology of EHO, the global view of collaterals, and the 3-D
      anatomy of SP axis could be well depicted and was well accepted by the surgeons.
      We conclude that CTP is an impressive new technique that can effectively evaluate
      pre- and postshunt cases of EHO.

PMID- 10899423
TI  - Emphysematous pyelonephritis- conversion of type i to type II appearance on
      serial CT studies.
AB  - Recently, emphysematous pyelonephritis (EPN) has been classified into two
      subtypes based on CT findings. We recently experienced a patient whose CT image
      changed from type I (extensive destruction of the renal parenchyma with a large
      amount of air density without any fluid collection) to type II (containing a
      large amount of fluid) during the course of conservative treatment. We believe
      that some patients with type I EPN can change to type II EPN.

PMID- 10899424
TI  - Spondylolysis of the upper lumbar spine. Radiological features.
AB  - To elucidate the radiological features of spondylolysis of the three upper lumbar
      vertebrae, review of radiology reports during an 8-year period was performed.
      Among 17 levels of defects in 14 patients, nine were unilateral. Among 25
      defects, nine had an atypical course. In eight of nine atypical defects, the
      direction was vertical at the inferolateral aspect, and horizontal at the
      superomedial aspect. The spondylolysis of the upper lumbar spine is often
      unilateral and the course of the defect is frequently atypical.

PMID- 10899425
TI  - Unusual case of lumbar synovial cyst.
AB  - Synovial cysts are extradural degenerative lesions associated with symptoms of
      lower back pain and radiculopathy. To our knowledge, all the reported cases of
      synovial cysts in literature were posterolateral in location (1-4). This case
      report describes the previously unreported midline location of the synovial cyst
      in the spinal canal and to increase the level of awareness of diagnosing these
      lesions in a central location, especially in light of the evaluation of lumbar
      radiculopathy.

PMID- 10899426
TI  - Hallux valgus and hallux rigidus: MRI findings.
AB  - The purpose of this article is to describe the MR findings of Hallux Valgus (HV)
      and Hallux Rigidus (HR). Twenty-four patients (11 with HV, 4 with HR, and 9 with
      both HV and HR) were studied at 1.5 Tesla MRI. Two separate observers evaluated
      the first ray blindly for the following signs: sesamoid position, sesamoid
      proliferation, hypertrophy of the median eminence, presence of a lateral facet,
      presence of an adventitial bursa, shape of the first metatarsal head, relative
      length of the first metatarsal, joint space loss, osteophytes (dorsalor lateral),
      marrow edema, geodes, subchondral sclerosis, intra-articular ossicle, and pes
      planus. The most common findings observed in HV were a hypertrophic medial
      eminence (95%), sesamoid proliferation (90%) and adventitial bursitis (70%). The
      most common findings observed in HR were osteophytes (77% and 69%), geodes, and
      marrow edema. We conclude that traditional routine radiograph signs of HV and HR
      may be applied to MR images.

PMID- 10899428
TI  - Alzheimer's amyloid fibrils: structure and assembly.
AB  - Structural studies of Alzheimer's amyloid fibrils have revealed information about
      the structure at different levels. The amyloid-beta peptide has been examined in
      various solvents and conditions and this has led to a model by which a
      conformational switching occurs from alpha-helix or random coil, to a beta-sheet
      structure. Amyloid fibril assembly proceeds by a nucleation dependent pathway
      leading to elongation of the fibrils. Along this pathway small oligomeric
      intermediates and short fibrillar structures (protofibrils) have been observed.
      In cross-section the fibril appears to be composed of several subfibrils or
      protofilaments. Each of these protofilaments is composed of beta-sheet structure
      in which hydrogen bonding occurs along the length of the fibre and the beta
      strands run perpendicular to the fibre axis. This hierarchy of structure is
      discussed in this review.

PMID- 10899427
TI  - Presenilin structure, function and role in Alzheimer disease.
AB  - Numerous missense mutations in the presenilins are associated with the autosomal
      dominant form of familial Alzheimer disease. Presenilin genes encode polytopic
      transmembrane proteins, which are processed by proteolytic cleavage and form high
      molecular-weight complexes under physiological conditions. The presenilins have
      been suggested to be functionally involved in developmental morphogenesis,
      unfolded protein responses and processing of selected proteins including the beta
      amyloid precursor protein. Although the underlying mechanism by which presenilin
      mutations lead to development of Alzheimer disease remains elusive, one
      consistent mutational effect is an overproduction of long-tailed amyloid beta
      peptides. Furthermore, presenilins interact with beta-catenin to form presenilin
      complexes, and the physiological and mutational effects are also observed in the
      catenin signal transduction pathway.

PMID- 10899429
TI  - Oligomerizaiton and fibril asssembly of the amyloid-beta protein.
AB  - In this chapter, we attempt to analyze the evolution of the amyloid-beta (Abeta)
      molecular structure from its inception as part of the Abeta precursor protein to
      its release by the secretases and its extrusion from membrane into an aqueous
      environment. Biophysical studies suggest that the Abeta peptide sustains a series
      of transitions from a molecule rich in alpha-helix to a molecule in which beta
      strands prevail. It is proposed that initially the extended C-termini of two
      opposing Abeta dimers form an antiparallel beta-sheet and that the subsequent
      addition of dimers generates a helical Abeta protofilament. Two or more
      protofilaments create a strand in which the hydrophobic core of the beta-sheets
      is shielded from the aqueous environment by the N-terminal polar domains of the
      Abeta dimers. Once the nucleation has occurred, the Abeta filament grows in
      length by the addition of dimers or tetramers.

PMID- 10899431
TI  - Neuronal models to study amyloid precursor protein expression and processing in
      vitro.

PMID- 10899430
TI  - Regulation of Alzheimer beta-amyloid precursor trafficking and metabolism.
AB  - Alzheimer's disease (AD) is characterized by the intracranial accumulation of the
      4 kDa amyloid-beta peptide (Abeta), following proteolysis of a approximately 700
      amino acid, integral membrane precursor, the Alzheimer amyloid precursor protein
      (APP). The best evidence causally linking APP to AD has been provided by the
      discovery of mutations within the APP coding sequence that segregate with disease
      phenotypes in autosomal dominant forms of familial AD (FAD). Though FAD is rare (
      < 10% of all AD), the hallmark features (amyloid plaques, neurofibrillary
      tangles, synaptic and neuronal loss, neurotransmitter deficits and dementia) are
      indistinguishable when FAD is compared with typical, common, 'non-familial', or
      sporadic, AD (SAD). Studies of some clinically relevant mutant APP molecules from
      FAD families have yielded evidence that APP mutations can lead to the enhanced
      generation or aggregability of Abeta, consistent with a pathogenic role in AD.
      Other genetic loci for FAD have been discovered which are distinct from the
      immediate regulatory and coding regions of the APP gene, indicating that defects
      in molecules other than APP can also specify cerebral amyloidogenesis and FAD. To
      date, all APP and non-APP FAD mutations can be demonstrated to have the common
      feature of promoting amyloidogenesis of Abeta. Epidemiological studies indicate
      that postmenopausal women on estrogen replacement therapy (ERT) have their
      relative risk of developing SAD diminished by about one third as compared with
      age-matched women not receiving ERT [M.X. Tang, D. Jacobs, Y. Stern, K. Marder,
      P. Schofield, B. Gurland, H. Andrews, R. Mayeux, Effect of estrogen during
      menopause on risk and age at onset of Alzheimer's disease, Lancet 348 (2000)
      429432]. Because of the key role of cerebral Abeta accumulation in initiating AD
      pathology, it is most attractive that estradiol might modulate SAD risk or age-at
      onset by inhibiting Abeta accumulation. A possible mechanistic basis for such a
      scenario is reviewed here.

PMID- 10899432
TI  - Transgenic mouse models of Alzheimer's disease.

PMID- 10899433
TI  - Approaches to discovery and characterization of inhibitors of amyloid beta
      peptide polymerization.
AB  - Polymerization of the amyloid beta-peptide (Abeta) has been identified as a major
      feature of the pathogenesis of Alzheimer's disease (AD). Inhibition of the
      formation of these toxic polymers of Abeta has thus emerged as an approach to
      developing therapeutics for AD. Techniques for studying Abeta polymerization
      include the use of fibril nucleation and extension assays in a variety of
      formats. Detection of polymeric forms of Abeta has been achieved using turbidity,
      dye binding, light scattering and toxicity among other methods. Direct and
      indirect methods have been described for the measurement of binding affinities
      for Abeta fibrils. Imaging techniques include electron microscopy, X-ray
      diffraction and atomic force microscopy. These techniques have been used to
      characterize different classes of compounds that inhibit the formation of Abeta
      polymers. These compounds include dyes such as Congo Red, the antibiotic
      rifampicin, the anthracycline 4'-iodo-4'-deoxydoxorubicin, and a large variety of
      Abeta-derived peptides and modified peptides, among other reported inhibitors.

PMID- 10899434
TI  - The role of apolipoprotein E in Alzheimer's disease: pharmacogenomic target
      selection.
AB  - The association of inheritance of different apolipoprotein E (APOE, gene; apoE,
      protein) alleles with the risk and rate of onset of Alzheimer's disease (AD) is
      now well established and widely confirmed. While there are now a collection of
      hypotheses concerning the specific relationship of APOE polymorphisms to various
      phenotypic manifestations of AD, no single compelling theory has been tested and
      universally accepted. The only clear fact emerging during the past 6 years is
      that differences in APOE genotype affect the average rate of disease onset as a
      predictable function of the inheritance of this polymorphic gene. Methods now
      exist to enable experimental designs to study the metabolic effects of inheriting
      different APOE alleles, addressing what differences that may be present for many
      years, perhaps over the entire lifetime, can lead to earlier or later
      manifestations of the disease and are therapeutically tractable. This review
      summarizes part of an experimental approach to identify biological pathways
      influenced by the different APOE polymorphisms that are relevant to the
      pathogenesis of AD.

PMID- 10899435
TI  - Properties of NACP/alpha-synuclein and its role in Alzheimer's disease.
AB  - The precursor of the non-amyloid beta/A4 protein (non-Abeta) component of
      Alzheimer's disease amyloid (NACP)/alpha-synuclein is the human homologue of
      alpha-synuclein, a member of a protein family which includes alpha-, beta- and
      gamma-synuclein. This protein is thought to be involved in neuronal plasticity
      because of its unique expression, mainly in the telencephalon during maturation.
      Consequently, disarrangement of NACP/alpha-synuclein might disrupt synaptic
      activity, resulting in memory disturbance. Previous studies have shown that
      damage to synaptic terminals is closely associated with global cognitive
      impairment and is an early event in the pathogenesis of Alzheimer's disease.
      Although the relationship between synaptic damage and amyloidogenesis is not
      clear, some proteins at the synaptic site have been implicated in both neuronal
      alteration and amyloid formation. Indeed, abnormal accumulation of both
      NACP/alpha-synuclein and Abeta precursor protein occurs at synapses of
      Alzheimer's patients. Other evidence suggests that NACP/alpha-synuclein is a
      component of the Lewy bodies found in patients with Parkinson's disease or
      dementia with Lewy bodies, and that a point mutation in this protein may be the
      cause of familial Parkinson's disease. Consequently, abnormal transport,
      metabolism or function of NACP/alpha-synuclein appears to impair synaptic
      function, which induces, at least in part, neuronal degeneration in several
      neurodegenerative diseases.

PMID- 10899436
TI  - Tau mutations in frontotemporal dementia FTDP-17 and their relevance for
      Alzheimer's disease.
AB  - Alzheimer's disease is characterised by the degeneration of selected populations
      of nerve cells that develop filamentous inclusions prior to degeneration. The
      neuronal inclusions of Alzheimer's disease are made of the microtubule-associated
      protein tau, in a hyperphosphorylated state. Abundant filamentous tau inclusions
      are not limited to Alzheimer's disease. They are the defining neuropathological
      characteristic of frontotemporal dementias, such as Pick's disease, and of
      progressive supranuclear palsy and corticobasal degeneration. The discovery of
      mutations in the tau gene in familial frontotemporal dementia and parkinsonism
      linked to chromosome 17 (FTDP-17) has provided a direct link between tau
      dysfunction and dementing disease. Known mutations produce either a reduced
      ability of tau to interact with microtubules, or an overproduction of tau
      isoforms with four microtubule-binding repeats. This leads in turn to the
      assembly of tau into filaments similar or identical to those found in Alzheimer's
      disease brain. Several missense mutations also have a stimulatory effect on
      heparin-induced tau filament formation. Assembly of tau into filaments may be the
      gain of toxic function that is believed to underlie the demise of affected brain
      cells.

PMID- 10899437
TI  - Structure of tau protein and assembly into paired helical filaments.
AB  - Over the past few years the systematic investigation of paired helical filament
      assembly from tau protein in vitro has become feasible. We review our current
      understanding of the structure and conformations of tau protein and how this
      affects tau's assembly into the pathological paired helical filaments in
      Alzheimer's disease.

PMID- 10899438
TI  - Role of the proteasome in Alzheimer's disease.
AB  - The proteasome is a multicatalytic complex involved in the degradation of
      polyubiquitinated proteins. Here we review the clues of a possible involvement of
      the proteasome in Alzheimer's disease neuropathology. Thus, we discuss the fact
      that the proteasome modulates the intracellular concentrations of presenilins 1
      and 2. These two proteins, when mutated, appear responsible for most of early
      onset forms of Alzheimer's disease and this is thought to be due to the
      exacerbation of the pathogenic pathway of the maturation of the beta-amyloid
      precursor protein. Controlling presenilins concentrations could have drastic
      repercussions on cell physiology as suggested by the fact that proteasome
      inhibitors drastically potentiate the 'normal' or 'pathogenic' presenilins
      phenotype related with betaAPP processing. The possibility of considering the
      proteasome as a potential target for therapeutic intervention in Alzheimer's
      disease is discussed.

PMID- 10899439
TI  - Oxidative stress in Alzheimer's disease.
AB  - Oxidative balance is emerging as an important issue in understanding the
      pathogenesis of Alzheimer's disease. Examination of Alzheimer's disease brain has
      demonstrated a great deal of oxidative damage, associated with both hallmark
      pathologies (senile plaques and neurofibrillary tangles) as well as in normal
      appearing pyramidal neurons. While this suggests that oxidative stress is a
      proximal event in Alzheimer's disease pathogenesis, the mechanisms by which redox
      balance is altered in the disease remains elusive. Determining which of the
      proposed sources of free radicals, which include mitochondrial dysfunction,
      amyloid-beta-mediated processes, transition metal accumulation and genetic
      factors like apolipoprotein E and presenilins, is responsible for redox imbalance
      will lead to a better understanding of Alzheimer's disease pathogenesis and novel
      therapeutic approaches.

PMID- 10899440
TI  - Cellular cofactors potentiating induction of stress and cytotoxicity by amyloid
      beta-peptide.
AB  - Insights into factors underlying causes of familial Alzheimer's disease (AD),
      such as mutant forms of beta-amyloid precursor protein and presenilins, and those
      conferring increased risk of sporadic AD, such as isoforms of apolipoprotein E
      and polymorphisms of alpha2-macroglobulin, have been rapidly emerging. However,
      mechanisms through which amyloid beta-peptide (Abeta), the fibrillogenic peptide
      most closely associated with neurotoxicity in AD, exerts its effects on cellular
      targets have only been more generally outlined. Late in the course of AD, when
      Abeta fibrils are abundant, non-specific interactions of amyloid with cellular
      elements are likely to induce broad cytotoxicity. However, early in AD, when
      concentrations of Abeta are much lower and extracellular deposits are infrequent,
      mechanisms underlying cellular dysfunction have not been clearly defined. The key
      issue in elucidating the means through which Abeta perturbs cellular properties
      early in AD is the possibility that protective therapy at such times may prevent
      cytotoxicity at a point when damage is still reversible. This brief review
      focusses on two cellular cofactors for Abeta-induced cellular perturbation: the
      cell surface immunoglobulin superfamily molecule RAGE (receptor for advanced
      glycation endproducts) and ABAD (Abeta binding alcohol dehydrogenase). Although
      final proof for the involvement of these cofactors in cellular dysfunction in AD
      must await the results of further in vivo experiments, their increased expression
      in AD brain, as well as other evidence described below, suggests the possibility
      of specific pathways for Abeta-induced cellular perturbation which could provide
      future therapeutic targets.

PMID- 10899441
TI  - The role of complement in Alzheimer's disease pathology.
AB  - Complement proteins are integral components of amyloid plaques and cerebral
      vascular amyloid in Alzheimer brains. They can be found at the earliest stages of
      amyloid deposition and their activation coincides with the clinical expression of
      Alzheimer's dementia. This review will examine the origins of complement in the
      brain and the role of beta-amyloid peptide (Abeta) in complement activation in
      Alzheimer's disease, an event that might serve as a nidus of chronic
      inflammation. Pharmacology therapies that may serve to inhibit Abeta-mediated
      complement activation will also be discussed.

PMID- 10899442
TI  - Biochemical detection of Abeta isoforms: implications for pathogenesis,
      diagnosis, and treatment of Alzheimer's disease.
AB  - Prior to the identification of the various abnormal proteins deposited as
      fibrillar aggregates in the Alzheimer's disease (AD) brain, there was tremendous
      controversy over the importance of the various lesions with respect to primacy in
      the pathology of AD. Nevertheless, based on analogy to systemic amyloidosis, many
      investigators believed that the amyloid deposits in AD played a causal role and
      that characterization of these deposits would hold the key to understanding this
      complex disease. Indeed, in retrospect, it was the initial biochemical
      purifications of the approximately 4 kDa amyloid beta-peptide (Abeta) from
      amyloid deposits in the mid 1980s that launched a new era of AD research (Glenner
      and Wong, Biochem. Biophys. Res. Commun. 122 (1984) 1121-1135; Wong et al., Proc.
      Natl. Acad Sci. USA 82 (1985) 8729 8732; and Masters et al., Proc. Natl. Acad
      Sci. USA 82 (1985) 4245-4249). Subsequent studies of the biology of Abeta
      together with genetic studies of AD have all supported the hypothesis that
      altered Abeta metabolism leading to aggregation plays a causal role in AD.
      Although there remains controversy as to whether Abeta deposited as classic
      amyloid or a smaller, aggregated, form causes AD, the relevance of studying the
      amyloid deposits has certainly been proven. Despite the significant advances in
      our understanding of the role of Abeta in AD pathogenesis, many important aspects
      of Abeta biology remain a mystery. This review will highlight those aspects of
      Abeta biology that have led to our increased understanding of the pathogenesis of
      AD as well as areas which warrant additional study.

PMID- 10899443
TI  - Diagnostic approaches to Alzheimer's disease.
AB  - The importance of obtaining an accurate and early diagnosis for Alzheimer's
      disease is now becoming recognized. Nonpharmacological as well as pharmacological
      therapies can be best initiated once a diagnosis is obtained. Biochemical markers
      to identify Alzheimer's disease have been sought for many years, with many
      candidates proposed. Recently criteria were established to evaluate putative
      diagnostic tests. Several biomarkers now show utility in identifying those with
      Alzheimer's disease. The ApoE e4 allele, while a risk factor rather than a
      deterministic gene, in the context of an individual with suspicion of AD has a
      positive predictive value of 94-98% and may come to have utility in predicting
      response to certain classes of pharmacological agents. Independent groups have
      shown that the markers in cerebrospinal fluid tau and Ab42 are, respectively,
      elevated and reduced in patients with AD versus other patient groups and that the
      lumbar puncture itself is usually well tolerated. For early-onset AD, sequencing
      presenilin 1 has come into use and the positive frequency is similar to that
      found in other genetic-based laboratory tests.

PMID- 10899444
TI  - Phenotypic manifestations associated with CAG-repeat expansion in the androgen
      receptor gene in male patients and heterozygous females: a clinical and molecular
      study of 30 families.
AB  - Spinal and bulbar muscular atrophy (Kennedy disease) is an adult form of X-linked
      motor neuron disease caused by the expansion of a polymorphic CAG-repeat sequence
      in the first exon of the androgen receptor gene. We studied clinical and
      molecular features of 36 patients and 19 heterozygous females. Phenotypic
      manifestations and disease severity broadly varied among our spinal and bulbar
      muscular atrophy patients. The size of CAG expansion significantly influences the
      age of disease onset, but neither clinical features nor disease severity. The
      majority of carrier women presented signs of chronic denervation at
      neurophysiological examination and, in three cases, low-amplitude sensory action
      potentials were recorded. Notably, a few women developed mild signs of bulbar
      motor neuron impairment later in life. The identification of a large number of
      patients by the use of the molecular test further supports the hypothesis that
      Kennedy disease had been previously underdiagnosed, probably because of the great
      variability of clinical presentation. Although an early diagnosis may not be
      crucial for treatment, given the lack of effective therapy, the molecular testing
      can be of great relevance for disease prognosis and genetic counseling.

PMID- 10899445
TI  - Childhood chronic inflammatory demyelinating polyneuropathy: clinical course and
      long-term outcome.
AB  - We reviewed the clinical history, electrophysiologic and pathologic findings, and
      response to therapy of 16 children with chronic inflammatory demyelinating
      polyneuropathy. The majority presented with lower limb weakness. Sensory loss was
      uncommon. The illness was monophasic in seven children, relapsing in six, and
      three had a slowly progressive course. All patients were treated with
      immunosuppressive agents. In 11, the initial treatment was prednisolone. All had
      at least a short-term response but five went on to develop a relapsing course.
      Intravenous immunoglobulin was the initial treatment in four patients. Three
      responded rapidly, with treatment being stopped after a maximum of 5 months. In
      resistant chronic inflammatory demyelinating neuropathy, in addition to
      prednisolone and immunoglobulin, plasma exchange, azathioprine, cyclosporine,
      methotrexate, cyclophosphamide and pulse methylprednisolone were tried at
      different times in different patients. On serial neurophysiologic testing slowing
      of nerve conduction persisted for long periods after clinical recovery. Follow-up
      was for an average of 10 years. When last seen 14 patients were asymptomatic, two
      having mild residual deficits. Childhood chronic inflammatory demyelinating
      neuropathy responds to conventional treatment and generally has a favourable long
      term outcome.

PMID- 10899446
TI  - Cerebrotendinous xanthomatosis. Controversies about nerve and muscle:
      observations in ten patients.
AB  - Neuromuscular characteristics were documented in ten patients with biochemically
      and genetically confirmed cerebrotendinous xanthomatosis. An array of genotypes
      was found in these patients. Only one patient complained of muscle weakness,
      while clinical signs of peripheral neuropathy were present in six patients.
      Electromyogram showed predominantly axonal neuropathy in seven patients.
      Neurogenic changes were seen in muscle biopsies of nine patients. Sural nerve
      biopsies of three patients showed features of axonal neuropathy. In addition, in
      one patient, extensive onion bulb formation was seen, which is indicative of a
      primarily demyelinating process. Five patients had normal mitochondrial
      respiratory chain enzyme activity. It is concluded that myopathy is not a feature
      of cerebrotendinous xanthomatosis and that the most prominent neuromuscular
      abnormality is sensorimotor axonal polyneuropathy.

PMID- 10899447
TI  - Neuromuscular syndrome associated with the 3291T-->C mutation of mitochondrial
      DNA: a second case.
AB  - A mutation was found in an Italian child affecting the gene encoding the
      mitochondrial transfer RNA for leucine (codon UUR). This mutation (3291T-->C) had
      previously been reported in a single Japanese patient. In contrast with the
      original patient, who suffered from early-onset mitochondrial encephalomyopathy,
      lactic acidosis and stroke-like episodes (MELAS), our patient presented an
      apparently isolated mild myopathy. Mutational analysis in the proband and her
      family showed that the mutation was heteroplasmic, and that its relative amount
      was positively correlated with the severity of the phenotype. These findings lead
      to the definitive confirmation that the 3291T-->C is indeed pathogenic. As
      commonly found in mitochondrial-DNA related disorders, also for this mutation
      different clinical manifestations can be associated with the same genetic
      abnormality.

PMID- 10899448
TI  - Clinico-electrophysiological correlation of extensor digitorum brevis muscle
      atrophy in children with charcot-marie-tooth disease 1A duplication.
AB  - The purpose of the study is to describe the electrophysiologic abnormalities
      accounting for the appearance and progression of extensor digitorum brevis (EDB)
      muscle atrophy in Charcot-Marie-Tooth-disease type 1A (CMT-1A) children. Twelve
      children with CMT-1A duplication were serially evaluated. Initial ages of clinico
      electrophysiological exams ranged from 1 month to 4 years (mean: 2 years) and
      final ages from 6 to 23 years (mean: 13). All subjects had two or more
      electrophysiological studies of the peroneal nerve. EDB atrophy was observed in
      two out of 12 (17%) patients by the age of 5, in eight out of ten (80%) examined
      between 5 and 9 years, and in all eight (100%) patients who had reached the
      second decade at the end. Nerve conduction maturation was systematically
      abnormal, but by age of 5 the mean values of nerve conduction parameters of
      peroneal nerve did not significantly differ from those in older patients.
      Compound muscle action potential (CMAP) amplitudes of EDB were reduced in 42% of
      cases initially and 100% upon last exam. Furthermore, a constant finding
      throughout the study was progressive attenuation of CMAPs, these becoming
      unobtainable in four cases. EDB muscle atrophy in CMT-1A children is an age
      dependent sign which is accounted for by gradual reduction of the distal peroneal
      nerve CMAP amplitudes.

PMID- 10899449
TI  - Immunohistochemical staining of dystrophin on formalin-fixed paraffin-embedded
      sections in Duchenne/Becker muscular dystrophy and manifesting carriers of
      Duchenne muscular dystrophy.
AB  - We succeeded in immunostaining of monoclonal anti-dystrophin antibodies on
      formalin-fixed and paraffin-embedded muscle sections from patients with Duchenne
      muscular dystrophy, patients with Becker muscular dystrophy, and manifesting
      carriers of Duchenne muscular dystrophy using Catalyzed Signal Amplification(TM)
      system. The Catalyzed Signal Amplification system is an extremely sensitive
      immunohistochemistry staining procedure based on the peroxidase-catalyzed
      deposition of a biotinylated phenolic compound. We used three mouse monoclonal
      antibodies: DYS1, DYS2, and DYS3. Muscle sections were treated using the Target
      Retrieval Solution(TM) and the Catalyzed Signal Amplification system. In control
      patients, DYS1 and DYS2 were stained at the sarcolemma, but DYS3 remained
      unstained. In Duchenne muscular dystrophy patients, DYS1 and DYS2 staining were
      undetected. In Becker muscular dystrophy patients, the immunolabeling of DYSI and
      DYS2 were weak and discontinuous. In manifesting carriers of Duchenne muscular
      dystrophy, DYS1 and DYS2 staining showed a mosaic pattern of dystrophin-positive
      fibers and dystrophin-negative fibers. DYS1 and DYS2 staining patterns of this
      study are similar to those of frozen sections using conventional methods
      previously reported. In cases from whom frozen muscle sections cannot be
      obtained, immunohistochemical dystrophin analysis using the Catalyzed Signal
      Amplification system will be beneficial for the diagnosis and the screening of
      neuromuscular diseases.

PMID- 10899450
TI  - Mitochondrial impairment of human muscle in Friedreich ataxia in vivo.
AB  - Friedreich ataxia occurs due to mutations in the gene encoding the mitochondrial
      protein frataxin. This (31)P magnetic resonance spectroscopy study on the calf
      muscle of Friedreich ataxia patients provides in vivo evidence of a severe
      impairment of mitochondrial function. Mitochondrial adenosine triphosphate
      resynthesis was studied by means of the post-exercise recovery of
      phosphocreatine. After ischemic exercise in calf muscles of all patients,
      phosphocreatine recovery was dramatically delayed. Time constants of recovery
      correlated with mutations of the frataxin gene, the age of the patients, and
      disease duration. (31)P magnetic resonance spectroscopy represents the first
      expedient tool for monitoring therapeutic trials in Friedreich ataxia non
      invasively.

PMID- 10899451
TI  - Adenosine- and 2-chloro-adenosine-induced cytopathic effects on myoblastic cells
      and myotubes: involvement of different intracellular mechanisms.
AB  - We recently suggested that, in muscular dystrophies, the excessive accumulation
      of adenosine as a result of an altered purine metabolism may contribute to
      progressive functional deterioration and muscle cell death. To verify this
      hypothesis, we have taken advantage of C2C12 myoblastic cells, which can be
      differentiated in vitro into multinucleated cells (myotubes). Exposure of both
      proliferating myoblasts and differentiated myotubes to adenosine or its
      metabolically-stable analog, 2-chloro-adenosine, resulted in apoptotic cell death
      and myotube disruption. Cytotoxicity by either nucleoside did not depend upon
      extracellular adenosine receptors, but, at least in part, by entry into cells via
      the membrane nitro-benzyl-thio-inosine-sensitive transporter. The adenosine
      kinase inhibitor, 5-iodotubercidin, prevented 2-chloro-adenosine-induced (but not
      adenosine-induced) effects, suggesting that an intracellular
      phosphorylation/activation reaction plays a key role in 2-chloro-adenosine
      mediated cytotoxicity. Conversely, adenosine cytotoxicity was aggravated by the
      addition of homocysteine, suggesting that adenosine effects may be due to the
      accumulation of S-adenosyl-homocysteine, which blocks intracellular methylation
      dependent reactions. Both nucleosides markedly disrupted the myotube structure
      via an effect on the actin cytoskeleton; however, also for myotubes, there were
      marked differences in the morphological alterations induced by these two
      nucleosides. These results show that adenosine and 2-chloro-adenosine induce
      apoptosis of myogenic cells via completely different metabolic pathways, and are
      consistent with the hypothesis that adenosine accumulation in dystrophic muscles
      may represent a novel pathogenetic pathway in muscle diseases.

PMID- 10899452
TI  - A homozygous missense mutation (A659D) in the myophosphorylase gene in a Spanish
      patient with McArdle's disease.
AB  - We identified a novel missense mutation in the myophosphorylase gene (PYGM) in a
      Spanish patient with McArdle's disease. This homozygous C-to-A mutation results
      in the replacement of a highly conserved alanine at amino acid position 659 with
      an aspartic acid in the C-terminal domain of the myophosphorylase gene protein,
      near binding sites for pyridoxal phosphate and glucose. Our data further expand
      the genetic heterogeneity in patients with McArdle's disease.

PMID- 10899453
TI  - A novel SURF1 mutation results in Leigh syndrome with peripheral neuropathy
      caused by cytochrome c oxidase deficiency.
AB  - We report on a 5-year-old boy with clinical and neuroradiological evidence of
      Leigh syndrome and peripheral neuropathy. Skeletal muscle biopsy showed decreased
      cytochrome c oxidase stain. Ultrastructurally, the nerve biopsy showed a defect
      of myelination. Biochemical analyses of muscle homogenate showed cytochrome c
      oxidase deficiency (15% residual activity). SURF1 gene analysis identified a
      novel homozygous nonsense mutation which predicts a truncated surf1 protein.

PMID- 10899454
TI  - Rhabdomyosarcoma rho(0) cells: isolation and characterization of a mitochondrial
      DNA depleted cell line with 'muscle-like' properties.
AB  - Mutations of mitochondrial DNA are a significant cause of neuromuscular disease.
      Pathological mutant mitochondrial DNA has been studied in control nuclear
      backgrounds. These experiments entailed transfer of patient-derived mitochondria
      to rho(0) cells that lack mtDNA. A limitation of these studies has been the fact
      that the control nuclear backgrounds were unrelated to the affected tissues of
      patients. Therefore a rhabdomyosarcoma cell line that has 'muscle-like'
      properties was tested to determine whether it could be depleted of mtDNA. A human
      rhabdomyosarcoma cell line was treated with the DNA intercalating dye ethidium
      bromide (3, 8-diamino-5-ethyl-6-phenylphenanthridinium bromide) for 45 days. The
      treatment induced complete and permanent loss of mitochondrial DNA (rho(0)) in
      the rhabdomyosarcoma cells, as mtDNA remained undetectable after 8 months of
      growth in medium without drug. Crucially, the rhabdomyosarcoma rho(0) cells
      retained the ability to differentiate into myotubes with expression of muscle
      specific isoenzymes. The rhabdomyosarcoma rho(0) cell line provides a model
      system for studying pathological mutant mtDNA in cells that more closely resemble
      human muscle than the hitherto available human rho(0) cell lines.

PMID- 10899455
TI  - 74th ENMC international workshop: mitochondrial diseases 19-20 november 1999,
      Naarden, the netherlands.

PMID- 10899456
TI  - Mathematical modelling of insect neuropeptide potencies. Are quantitatively
      predictive models possible?
AB  - The potencies of natural adipokinetic hormones and synthetic variants have been
      determined in Locusta migratoria using the lipid mobilisation assay in vivo,
      and/or the acetate uptake assay in vitro. These data are combinations of
      previously published and unpublished data (a total of sixty-nine analogues), and
      form data sets for the construction of mathematical models of the hormone
      potencies. The sequence variations of amino acids in both natural and artificial
      adipokinetic hormone analogues were described using continuous descriptor scales
      z(1)', z(2)', and z(3)', each previously published scale being derived from
      various properties of the amino acids. By means of these z'-scales and partial
      least squares regression we attempted to model the potencies in Locusta
      migratoria of adipokinetic hormones in the two assays. Correlations (r(2) values)
      between predicted and actual potencies of the different peptides were up to 0.73.
      We discuss the potential of the partial least squares method for formulating
      quantitative relationships between different hormone structures and their
      potencies, and describe how the procedure might be used in structure-activity
      prediction with the construction of an optimised peptide data set.

PMID- 10899457
TI  - The piggyBac element is capable of precise excision and transposition in cells
      and embryos of the mosquito, Anopheles gambiae.
AB  - The piggyBac transposable element was tested for transposition activity in
      plasmid-based excision and inter-plasmid transposition assays to determine if
      this element would function in Anopheles gambiae cells and embryos. In the Mos55
      cell line, precise excision of the piggyBac element was observed only in the
      presence of a helper plasmid. Excision occurred at a rate of 1 event per 1000
      donor plasmids screened. Precise excision of the piggyBac element was also
      observed in injected An. gambiae embryos, but at a lower rate of 1 excision per
      5000 donor plasmids. Transposition of the marked piggyBac element into a target
      plasmid occurred in An. gambiae cells at a rate of 1 transposition event per
      24,000 donor plasmids. The piggyBac element transposed in a precise manner, with
      the TTAA target site being duplicated upon insertion, in 56% of transpositions
      observed, and only in the presence of the piggyBac helper. The remaining
      transpositions resulted in a deletion of target sequence, a novel observation for
      the phenomenon of piggyBac element insertion. 'Hot spots' for insertion into the
      target plasmid were observed, with 25 of 34 events involving one particular site.
      These results are the first demonstration of the precise mobility of piggyBac in
      this malaria vector and suggest that the lepidopteran piggyBac transposon is a
      candidate element for germline transformation of anopheline mosquitoes.

PMID- 10899458
TI  - Sunlight-activated insecticides: historical background and mechanisms of
      phototoxic activity.
AB  - Several photosensitizing agents, which are activated by illumination with
      sunlight or artificial light sources, have been shown to be accumulated in
      significant amounts by a variety of insects when they are administered in
      association with suitable baits. The subsequent exposure of such insects to
      UV/visible light leads to a significant drop in survival. Of the photosensitizers
      tested so far, xanthenes (e.g. phloxin B) and porphyrins (e.g. haematoporphyrin)
      appear to be endowed with the highest photoinsecticidal activity. In particular,
      porphyrins absorb essentially all the UV/visible light wavelengths in the
      emission spectrum of the sun; hence they are active at very low doses. Thus, 1 h
      irradiation of Ceratitis capitata, Bactrocera oleae (also known as Dacus oleae)
      or Stomoxys calcitrans which ingested a few nanomoles of porphyrin per fly with
      light intensities of the order of 1000 microE s(-1) m(-2) causes about 100% death
      in laboratory tests. Present evidence suggests that such photosensitizers act on
      the membranes of the midgut with consequent feeding inhibition, as well as on the
      neuromuscular sheath. No apparent onset of photoresistance has been observed. The
      rapid photobleaching of xanthenes and porphyrins when illuminated by visible
      light, as well as the lack of significant toxicity of such compounds in the dark,
      minimizes the risk of an important environmental impact of such photoinsecticidal
      agents.

PMID- 10899459
TI  - Expression and translocation of Drosophila nuclear encoded cytochrome b(5)
      proteins to mitochondria.
AB  - DNA sequence studies of cytochrome b(5) (Cyt-b) genes from Drosophila
      melanogaster and Drosophila virilis predict that the Drosophila Cyt-b proteins
      are extremely hydrophobic and have at least eight potential transmembrane
      spanning domains. Primary protein sequence analysis also predicts that the Cyt-b
      proteins have mitochondrial targeting sequences and they contain sites for
      potential post-translational modification similar to other cytochrome proteins.
      We report the characterization of the cytochrome b(5) proteins from Drosophila
      melanogaster and Drosophila virilis. We have used a Drosophila cytochrome b(5)
      specific antibody to demonstrate that cytochrome b(5) proteins are expressed in
      muscle-containing tissues in the fly. We also provide evidence that the nuclear
      encoded cytochrome b(5) protein that contains a mitochondrial targeting sequence
      is translocated to mitochondria.

PMID- 10899460
TI  - Host hemolymph proteins and protein digestion in larval Habrobracon hebetor
      (Hymenoptera: braconidae).
AB  - Host plasma proteins and protein digestion in larval parasitoids were studied
      during trophic interactions of the ectoparasitoid Habrobracon hebetor Say
      (Hymenoptera: Braconidae), with a host, larvae of the Indianmeal moth, Plodia
      interpunctella Hubner (Lepidoptera: Pyralidae). We could detect no apparent
      differences in host hemolymph protein patterns up to 72 h after paralysation
      and/or parasitization by H. hebetor. A 190 kDa putative apolipophorin I present
      in host hemolymph could not be detected in the midguts of feeding H. hebetor
      larvae indicating that it is rapidly digested. The major 60 kDa storage proteins
      (putative hexamerins) in host hemolymph were detected in the parasitoid midgut
      and were completely digested 24 h after cessation of feeding and the beginning of
      cocoon formation. Host hemolymph had a pH of about 6.4. The pH optima of the
      midgut proteinases in the larval parasitoid were in the alkaline region, but
      midgut fluid in feeding parasitoid larvae was about pH 6. 8. Based on enzyme
      activity against selected artificial proteinase substrates including azocasein, N
      alpha-benzoyl-L-Arg p-nitroanilide (BApNA), succinyl-Ala-Ala-Pro-Phe p
      nitroanilide (SAAPFpNA), succinyl-Ala-Ala-Pro-Leu p-nitroanilide (SAAPLpNA), and
      inhibition by selected proteinase inhibitors, serine proteinases appear to be the
      predominant class of enzymes involved in protein digestion in the midguts of H.
      hebetor. There is also an active aminopeptidase (LpNA) associated with the
      microsomal fraction of midgut preparations. There was no evidence for preoral
      digestion or ingestion of proteinases from host hemolymph by the parasitoid
      larva. There was a very active BApNAase in the soluble fraction of midgut
      extracts. This activity increased on a per midgut basis up to 24 h after the
      beginning of cocoon formation but decreased rapidly by 48 h. Two major (P1 and
      P3) and several minor proteinases were detected in midgut extracts of H. hebetor
      analysed with gelatin zymograms. The apparent molecular mass of P1 varied from 95
      to 49 kDa depending on protein loading. P3 had an apparent molecular mass of 39
      kDa that was independent of protein loading. In summary, electrophoretic evidence
      indicates that host hemolymph protein patterns do not change significantly for at
      least 72 h after paralysation by H. hebetor. The role, if any, of envenomization
      in preventing breakdown of hemolymph proteins during this time remains to be
      determined. Because the predominant host hemolymph proteins, a putative
      apolipophorin I and the putative hexamerins, are readily digested by the serine
      proteinases present in the midguts of this parasitoid larva, these or similar
      proteins would provide an easily digested source of dietary amino acids that
      could be used for development of artificial diets for this beneficial insect.

PMID- 10899461
TI  - Isolation and identification of cell hypertrophy-inducing substances in the gall
      forming aphid Colopha moriokaensis.
AB  - The insect galls on the leaves of Zelkova serrata were formed by the aphid
      Colopha moriokaensis. The crude extracts of the gall-forming aphid showed
      hypertrophy-inducing activity against the cultured cells of Z. serrata. Bioassay
      guided fractionation of the extracts led to isolation of three triacylglycerides
      containing (E,E, E)-octa-2,4,6-trienoic acid.

PMID- 10899462
TI  - Purification, characterization and molecular cloning of prophenoloxidases from
      Sarcophaga bullata.
AB  - Prophenoloxidase (PPO) is a key enzyme associated with both melanin biosynthesis
      and sclerotization in insects. This enzyme is involved in three physiologically
      important processes viz., cuticular hardening, defense reactions and wound
      healing in insects. It was isolated from the larval hemolymph of Sarcophaga
      bullata and purified by employing ammonium sulfate precipitation, Phenyl
      Sepharose chromatography, DEAE-Sepharose chromatography, and Sephacryl S-200
      column chromatography. The purified enzyme exhibited two closely moving bands on
      7.5% SDS-PAGE under denaturing conditions. From the estimates of molecular weight
      on Sephacryl S-100, TSK-3000 HPLC column and SDS-PAGE, which ranged from 90,000
      to 100,000, it was inferred that the enzyme is made up of a single polypeptide
      chain. Activation of PPO (K(a)=40 microM) was achieved by the cationic detergent,
      cetyl pyridinium chloride below its critical micellar concentration (0.8 mM)
      indicating that the detergent molecules are binding specifically to the PPO and
      causing the activation. Neither anionic, nor nonionic (or zwitterionic)
      detergents activated the PPO. The active enzyme exhibited wide substrate
      specificity and marked thermal unstability. Using primers designed to conserved
      amino acid sequences from known PPOs, we PCR amplified and cloned two PPO genes
      from the sarcophagid larvae. The clones encoded polypeptides of 685 and 691 amino
      acids. They contained two distinct copper binding regions and lacked the signal
      peptide sequence. They showed a high degree of homology to dipteran PPOs. Both
      contained putative thiol ester site, two proteolytic activation sites and a
      conserved C-terminal region common to all known PPOs.

PMID- 10899463
TI  - Identification of a point mutation in an esterase gene in different populations
      of the southern cattle tick, Boophilus microplus.
AB  - Two esterase cDNA sequences were obtained from susceptible and organophosphorus
      resistant strains of Boophilus microplus. Both sequences have a high degree of
      homology to carboxylesterase B. One gene has identical sequences in both strains
      and the other showed two point mutations. One mutation produces an amino acid
      substitution when the amino acid sequence is deduced, this mutation was detected
      in six different populations susceptible and resistant to insecticides, but a
      pyrethroid resistant strain was the only one that showed only the mutant allele.
      Identification of this mutation and the strong signal detected in southern blot
      with this strain, suggest that esterases are contributing to detoxification of
      pyrethroid compounds, as a resistant mechanism in Mexican strains of the southern
      cattle tick.

PMID- 10899464
TI  - cDNA cloning, biochemical characterization and inhibition by plant inhibitors of
      the alpha-amylases of the Western corn rootworm, Diabrotica virgifera virgifera.
AB  - We report the characterization and cDNA cloning of two alpha-amylase isozymes
      from larvae of the Western corn rootworm (Diabrotica virgifera virgifera
      LeConte). Larvae raised on artificial media have very low levels of amylase
      activity, and much higher levels are found in larvae raised on maize seedlings.
      At pH 5.7, the optimum pH for enzyme activity, the alpha-amylases are
      substantially but not completely inhibited by amylase inhibitors from the common
      bean (Phaseolus vulgaris) and from wheat (Triticum aestivum). Using the reverse
      transcriptase polymerase chain reaction (RT-PCR), we cloned two cDNAs with 83%
      amino acid identity that encode alpha-amylase-like polypeptides. Expression of
      one of the two cDNAs in insect cells with a baculovirus vector shows that this
      cDNA encodes an active amylase with a mobility that corresponds to that of one of
      the two isozymes present in larval extracts. The expressed enzyme is
      substantially inhibited by the same two inhibitors. We also show that expression
      in Arabidopsis of the cDNA that encodes the amylase inhibitor AI-1 of the common
      bean results in the accumulation of active inhibitor in the roots, and the
      results are discussed with reference to the possibility of using amylase
      inhibitors as a strategy to genetically engineer maize plants that are resistant
      to Western corn rootworm larvae.

PMID- 10899465
TI  - Novel point mutations in the German cockroach para sodium channel gene are
      associated with knockdown resistance (kdr) to pyrethroid insecticides.
AB  - Knockdown resistance (kdr) to pyrethroid insecticides has been attributed to
      point mutations in the para sodium channel gene in more than a half dozen insect
      pest species. In this study, we identified two novel para mutations in five
      highly resistant kdr-type German cockroach strains. The two mutations, from
      glutamic acid (E434) to lysine (K434) and from cysteine (C764) to arginine
      (R764), respectively, are located in the first intracellular linker connecting
      domains I and II. E434K is located near the beginning of the linker (closest to
      domain I), whereas C764R is found toward the end of the linker (closest to domain
      II). Two additional mutations from aspartic acid (D58) to glycine (G58), and from
      proline (P1880) to leucine (L1888), respectively, were found in one of the
      resistant strains. The four mutations coexist with the previously identified
      leucine to phenylalanine (L993F) kdr mutation in IIS6, and are present only in
      the highly resistant individuals of a given strain. These findings suggest that
      these mutations might be responsible for high levels of knockdown resistance
      toward pyrethroid insecticides in the German cockroach.

PMID- 10899466
TI  - ADHD in adolescence.

PMID- 10899467
TI  - Adolescents' understanding of social class: a comparison of white upper middle
      class and working class youth.
AB  - PURPOSE: Social class is increasingly being recognized as an important factor in
      the development of population-based variation in health among teens. However,
      little consensus exists regarding its measurement or conceptualization. METHODS:
      This study examined beliefs about social class of 48 working class and 50 upper
      middle class 16-year-old, white teens. RESULTS: Working class teens were more
      likely to misclassify themselves with regard to social class position.
      Significant class differences were present in beliefs regarding social mobility,
      parents' equity, equality of opportunity within society, and financial status as
      adults. How this conceptualization of social class translates into population
      based variation in health remains an important area for further inquiry.

PMID- 10899468
TI  - Adolescent motor vehicle crashes: the relationship between behavioral factors and
      self-reported injury.
AB  - PURPOSE: To examine the relative importance of demographic and behavioral
      factors, as well as alcohol use, in motor vehicle crash (MVC)-related injuries in
      an adolescent sample. METHODS: Data were collected from two samples of
      adolescents. In Study 1, a total of 1576 9th through 12th graders from three
      different high schools provided information on risk-taking behavior and injuries
      experienced during the previous six months. Study 2 involved a more fine-grained
      analysis of behavioral factors related to MVC-related injuries. A sample of 573
      adolescent males from an all-boys parochial high school completed questionnaires
      assessing risk-taking, attention and behavior problems, alcohol use, driving
      behavior, and self-reported injury. RESULTS: Rates of self-reported MVC-related
      injuries for a 6-month period were consistent across the two studies, ranging
      from 10% in the mixed-gender sample to 16% in the all-male sample. Consistent
      with previous findings, males reported more frequent MVC-related injuries and
      higher rates of risk-taking behavior. In Study 1, age and risk-taking behaviors
      were predictive of injuries while riding or driving in a car. In the all-male
      sample, risk-taking behavior and conduct problems were significant predictors of
      MVC-related injuries. CONCLUSIONS: Risk-taking is a consistent predictor of both
      general and MVC-related injuries. Intervention efforts with adolescents may be
      targeted at increasing safe driving strategies as well as decreasing risk-taking
      behaviors.

PMID- 10899469
TI  - Young drivers' health attitudes and intentions to drink and drive.
AB  - PURPOSE: To evaluate young drivers' intentions to drink and drive in the context
      of a health attitude model, the Protection Motivation Theory (PMT). METHODS:
      Licensed drivers attending college and ranging from 17 to 20 years of age (n =
      304) completed questionnaires assessing PMT variables in the context of drinking
      and driving. More than half the sample consisted of females (62%) and most were
      white (89%). The drivers rated the extent to which they found drinking and
      driving to be personally rewarding, their perceived vulnerability to the risks of
      drinking and driving, the severity of the risks, the response efficacy of
      alternative adaptive responses to drinking and driving, their self-efficacy for
      implementing alternative responses, and the response costs associated with the
      responses. The relationship between PMT variables and drivers' intention to drink
      and drive was tested using hierarchical multiple regression analyses with
      attitudes concerning drinking and driving (rewards, vulnerability, and severity)
      entered in the regression equation first, followed by attitudes concerning
      alternative adaptive responses (response efficacy, self-efficacy, and response
      costs). RESULTS: The PMT model was found to predict intentions to drink and
      drive. Young drivers who perceived rewards for drinking and driving and who felt
      vulnerable to the risks of drinking and driving were significantly more likely to
      report intentions to drink and drive. Attitudes about alternative adaptive
      responses to drinking and driving, including perceiving low self-efficacy for
      implementing alternative responses and perceiving personal costs for engaging in
      alternative options, also contributed to drivers' intentions to drink and drive.
      CONCLUSIONS: Although teenaged drivers are well informed of the dangers of
      drinking and driving, they still put themselves and others at risk by driving
      after consuming alcohol. Health professionals promoting safer alternatives might
      consider how young drivers' attitudes about both drinking and driving and
      alternative adaptive responses contribute to their intentions to drink and drive.

PMID- 10899470
TI  - Associations of sociodemographic, psychosocial, and behavioral factors with
      sexual risk and sexually transmitted diseases in teen clinic patients.
AB  - PURPOSE: To examine the influence of sociodemographic characteristics, sexually
      transmitted disease (STD)/human immunodeficiency virus knowledge, and
      psychosocial and behavioral risk factors on sexual risk and STDs in adolescents
      using constructs from the Information, Motivation, and Behavioral Skills model
      (IMB). METHODS: A convenience sample of 303 sexually experienced, racially
      diverse adolescents (mean age 16.7 years, 57.9% female) who were seeking health
      care at a general health maintenance organization teen clinic were recruited for
      the study and completed a self-reported questionnaire which assessed
      sociodemographic, knowledge, and psychosocial factors, risk behaviors, and
      history of STDs. Multiple regression analyses were used to assess factors
      associated with sexual risk behavior and STD history. RESULTS: Many of the study
      participants were at risk for STDs; 43.8% had four or more lifetime sexual
      partners, 62.8% did not consistently use condoms, 21.1% had a history of
      pregnancy or impregnation, and 28.2% had a history of STDs. A multiple linear
      regression model to assess factors associated with sexual risk behavior (a nine
      item index) indicate that perceptions of higher STD risk, perceptions that
      friends engage in risk behaviors, perceptions that friends will not support their
      STD risk-reduction efforts, knowing someone of a similar age who has had an STD,
      and having no intention of using condoms in the future are significantly
      associated with sexual behavioral risk (R(2) =.22, p <.000). A logistic
      regression model to examine history of STDs reveals that teens who are female,
      African-American, frequently use marijuana, have an older steady sexual partner,
      have a history of pregnancy or impregnation, have a greater number of lifetime
      sexual partners, and perceive that monogamy will not decrease STD risk are
      significantly more likely to report a history of STDs. CONCLUSIONS:
      Sociodemographic factors and constructs of the IMB model are associated with
      adolescents' risk and acquisition of STDs. Teens with such risk profiles should
      be targeted for risk-reduction intervention.

PMID- 10899471
TI  - Use of birth control pills, condoms, and withdrawal among U.S. high school
      students.
AB  - PURPOSE: To examine the use of contraception at last sexual intercourse among
      currently sexually active adolescents. METHODS: We analyzed data from national
      school-based Youth Risk Behavior Surveys (YRBS) conducted in 1991, 1993, 1995,
      and 1997. The YRBS is a self-administered, anonymous survey which uses a national
      probability sample of U.S. students in public and private schools from grades 9
      through 12. RESULTS: From 1991 to 1997, condom use significantly increased (from
      46% to 57%), birth control pill use decreased (from 21% to 17%), and use of
      withdrawal significantly decreased (from 18% to 13%). In 1997, although more
      students were using condoms, 13% reported using withdrawal and 15% reported using
      no method to prevent pregnancy at last sexual intercourse. In 1997, condom use
      among females was significantly lower in the 9th grade than in the 12th grade (p
      <.001), whereas birth control pill use was higher (p <.001) and use of withdrawal
      remained stable. Among males, condom use and withdrawal use remained stable from
      9th to 12th grade, whereas birth control pill use by their partner increased (p
      <.001). CONCLUSIONS: Inadequate contraceptive use among sexually active
      adolescents continues to be a major public health problem in the United States.
      For young people who will not remain sexually abstinent, families, health care
      providers, schools, and other influential societal institutions should promote
      the correct and continued use of condoms as essential protection against sexually
      transmitted diseases and human immunodeficiency virus infection.

PMID- 10899472
TI  - Trauma-triggered migraine and acute confusional migraine.

PMID- 10899473
TI  - Vocal cord dysfunction.

PMID- 10899474
TI  - Trends in injury mortality among young people in the European Union: a report
      from the EURORISC working group.
AB  - PURPOSE: To examine the trends in injury mortality among young people aged 15-24
      years residing in the 15 current member states of the European Union between 1984
      and 1993. METHODS: As part of a European Commission-funded project entitled
      European Review of Injury Surveillance and Control (EURORISC), mortality data for
      all externally caused physical injuries (International Classification of Disease
      Codes E800-999) were obtained from the World Health Organization. Data were
      analyzed to generate age-specific injury mortality rates and proportional
      differences in rates over the study period. Linear regression was used to
      represent the linear component of the mortality profile. RESULTS: Almost a
      quarter of a million young people died as a result of sustaining an externally
      caused physical injury (either unintentional or intentional) in the study
      countries between 1984 and 1993. Injury accounted for two-thirds of all deaths in
      this age group. Over three-quarters (76%) of deaths were due to unintentional
      injury, a further 17% to self-inflicted injuries, and the remaining 7% to
      homicide and other violent causes. Motor vehicle traffic fatalities accounted for
      84% of unintentional injury deaths. Although a decline in injury mortality was
      observed throughout Europe, rates of mortality owing to both unintentional
      injuries and suicide varied widely among study countries at both the beginning
      and end of the study period. CONCLUSIONS: Whereas injury mortality rates in young
      people in most European countries are lower than in other parts of the world
      (including the United States), injuries represent a major public health problem
      in the European Union. The death toll from motor vehicle traffic crashes is a
      particular cause for concern.

PMID- 10899476
TI  - Costly signaling and torch fishing on Ifaluk atoll.
AB  - In this paper I evaluate the merit of costly signaling theory (CST) as a paradigm
      for understanding why men of Ifaluk atoll torch fish. I argue that torch fishing
      is a handicap that signals men's productivity. Consistent with CST, torch fishing
      is observed by the predicted audience (women), energetically costly to perform,
      and a reliable indicator of the frequency a man fishes during the trade wind
      season. Contrary to expectations of who should benefit from torch fishing and
      consequently participate, torch fishers are not primarily young and unmarried.
      Torch fishers, however, are predominately from the matriline that owns the canoe
      on which they fish, suggesting that torch fishing also signals the productivity
      of a matriline. Although these results support the possibility that torch fishing
      is a handicap, no data are presented which demonstrate that torch fishers achieve
      any gains from sending the costly signal. This shortcoming and other directions
      for future research on Ifaluk foraging decisions are discussed.

PMID- 10899475
TI  - The determinants of sexual intercourse before age 16.
AB  - PURPOSE: To identify risk and protective factors for initiation of sexual
      intercourse before age 16 years at the level of the individual, family, and
      school. METHODS: A longitudinal study based on a cohort of 1020 people born in
      Dunedin, New Zealand in 1972/73 and followed up to age 21 years. Demographic
      characteristics of the sample were similar to the New Zealand population of that
      age, except that a smaller proportion (3%) were Maori or Pacific Island
      Polynesian. Information on individual, family and school factors was collected by
      interview with parents at ages 3, 5, 7 and 9 years and then by postal
      questionnaire two-yearly up to 15 years. Subjects were assessed two-yearly from
      age 3 years and interviewed about their behaviours and ambitions at ages 11, 13,
      and 15 years. Questions about age at first intercourse were asked by computer at
      age 21 years. Multivariate logistic regression was used to model associations
      with age of first intercourse less than 16 years. RESULTS: Data on age at first
      intercourse were available for 926/1020 (91%) of surviving members of the cohort
      assembled at age 3 years. Overall 27.5% of males and 31.7% of females reported
      sexual intercourse before age 16 years. In multivariate analyses the independent
      predictors for early sexual initiation for males were: not having outside home
      interests at age 13 years, no religious activity at age 11 years, not being
      attached to school at age 15 years, a low reading score, and a diagnosis of
      conduct disorder in early adolescence. For females, independent predictors were:
      socioeconomic status in the middle range, mother having her first child before
      age 20 years, IQ in the middle range, not being attached to school, being in
      trouble at school, planning to leave school early, cigarette smoking and higher
      self-esteem score. CONCLUSIONS: Individual and school factors appear to be more
      important than family composition or socioeconomic status in the decision to have
      sexual intercourse before age 16 years. The lowering of age at first intercourse
      may be partly a cohort effect related to high rates of teenage childbearing in
      the mothers' generation, and to changes in social acceptability of early sexual
      behaviour.

PMID- 10899477
TI  - Turtle hunting and tombstone opening. public generosity as costly signaling.
AB  - Costly signaling theory (CST) offers an explanation of generosity and collective
      action that contrasts sharply with explanations based on conditional reciprocity.
      This makes it particularly relevant to situations involving widespread
      unconditional provisioning of collective goods. We provide a preliminary
      application of CST to ethnographic data on turtle hunting and public feasting
      among the Meriam of Torres Strait, Australia. Turtle hunting appears to meet the
      key conditions specified in CST: it is (1) an honest signal of underlying
      abilities such as strength, risk-taking, skill, and leadership; (2) costly in
      ways not subject to reciprocation; (3) an effective means of broadcasting
      signals, since the collective good (a feast) attracts a large audience; and (4)
      seems to provide benefits to signalers (turtle hunters) as well as recipients
      (audience). We conclude with some suggestions as to the broader implications of
      this research, and the costly signaling paradigm in general, for understanding
      collective action and generosity in human social groups.

PMID- 10899478
TI  - "It's a Wonderful Life". signaling generosity among the Ache of Paraguay.
AB  - Intensive food sharing among foragers and horticulturists is commonly explained
      as a means of reducing the risk of daily shortfalls, ensuring adequate daily
      consumption for all group members who actively pool resources. Consistently high
      food producers who give more than they receive, however, gain the least risk
      reduction benefit from this daily pooling because they are the least likely to go
      without food on any given day. Why then do some high producers consistently share
      food, and why do some average producers share proportionally more food than
      others? We propose that although these individuals may not receive the same
      amounts they give (i.e., strict Tit-for-Tat), one explanation for their
      generosity is that they receive additional food during hard times. These include
      brief episodes of sickness, disease, injury, or accidents-fairly common events in
      traditional societies that can render individuals incapable of producing food,
      thereby having long-term effects on morbidity and fecundity and ultimately on
      lifetime reproductive success. Data collected among the Ache, a group of South
      American forager-horticulturists, indicate that those who shared and produced
      more than average (signaling cooperative intent and/or ability to produce) were
      rewarded with more food from more people when injured or sick than those who
      shared and produced below average. These results, framed within the context of
      tradeoffs between short-term and long-term fitness, may provide insight into
      motivations behind costly expenditures for establishing and reinforcing status
      and reputation.

PMID- 10899479
TI  - A detailed analysis of menstrual blood loss in women using Norplant and Nestorone
      progestogen-only contraceptive implants or vaginal rings.
AB  - Changes to the pattern of menstrual bleeding are almost universal in women using
      progestogen-only methods of contraception, and are an important cause of
      discontinuation of these methods. The present study was designed to explore the
      changes in menstrual bleeding patterns and objectively measure menstrual blood
      loss (MBL) in 110 women before and during one year of use of 4 different
      progestogen-only contraceptives: Norplant subdermal levonorgestrel implants;
      Nestorone progestogen 4-cm or 6-cm implants nominally delivering 100 microg or
      150 microg daily; or a vaginal ring (CVR) delivering 100 microg of Nestorone
      (NES) daily (CVR users were limited to only 6 months of use). Groups could not be
      directly compared because of the differences in numbers of subjects and durations
      of treatment. The total MBL during each of the three 8-week collection periods
      during treatment decreased significantly in each group compared to the total
      blood loss in the two control cycles (greater than 50% decrease in all groups
      during the first 6 months), although the differences between individual women at
      the extremes remained considerable. The highest blood loss measured on any single
      day during the treatment collection periods was significantly reduced (p <0.001)
      in users of all four devices in all three collection periods compared to the
      control period (CVR users did not have a 3rd collection period). The Nestorone
      releasing CVR was associated with an 88% reduction in mean MBL and a high
      incidence of amenorrhea at 6 months. There was considerable variation in
      percentage reduction in total blood loss at 6 and 12 months between individual
      women ranging from 100% (women with amenorrhea) to a small minority experiencing
      an increase compared with control cycles. The increases in measured blood loss
      during treatment were almost entirely in women with light bleeding in the control
      period and were related to prolonged episodes of light bleeding rather than heavy
      bleeding. Women contemplating use of a progestogen-only contraceptive method need
      to be counseled about alterations to the menstrual cycle but can be reassured
      that total blood loss will usually be much less than with normal cycles.

PMID- 10899480
TI  - Using complete breastfeeding and lactational amenorrhoea as birth spacing
      methods.
AB  - The aim of this study was to evaluate the effectiveness of lactational
      amenorrhoea and to determine the relationship between extended breastfeeding and
      the return of fertility. Breastfeeding pattern, basal body temperature, cervical
      mucus, salivary ferning, vaginal blood discharge, frequency of sexual
      intercourse, and the presence of ovulation in the first cycle after the
      resumption of menses with ultrasonography were evaluated in 40 women. All
      subjects completed the study with only one case of incomplete breastfeeding. No
      pregnancies were observed. The mean number of feeding sessions and mean interval
      between sessions decreased significantly (p <0.01) during the first six months
      postpartum (7.5 +/- 1.3 after 60 days postpartum vs. 5.7 +/- 2.1 after 180 days,
      and 3.6 +/- 0.8 vs. 5.1 +/- 0.9, respectively). Eight women (20%) menstruated
      before weaning, but none had an adequate thermal shift, while 32 (80%) had their
      first vaginal bleeding after weaning with 12 (37.5%) registering an adequate
      thermal shift. Both basal body temperature and salivary ferning proved to be
      suggestive of ovarian activity, while mucus characteristics were not reliable in
      identifying fertile periods. Our study showed that breastfeeding associated with
      lactational amenorrhoea proved to be a good method of postpartum fertility
      control. Since the importance of supplementation is still debated, it is
      recommended that a "complete" breastfeeding program be used.

PMID- 10899481
TI  - Evidence that treatment with monophasic oral contraceptive formulations
      containing ethinylestradiol plus gestodene reduces bone resorption in young
      women.
AB  - The aim of the study was to evaluate if a pill containing the same dose of the
      same type of progestin compound (gestodene, GES, 75 microg) but different doses
      of ethinylestradiol (EE2) (20 or 30 microg) differently influences specific
      markers of bone resorption (urinary levels of pyridinoline (PYR) and
      dexoxypyridinoline (D-PYR)). During the 12 months of the study a significant
      decrease of urinary levels of PYR and D-PYR was found in 2 groups of young post
      adolescent women taking the pills with 20 and 30 microg of EE2 in comparison with
      control women (subjects of the same age group with normal menstrual cycle who did
      not use contraception). In women taking pills with 20 or 30 microg EE2, the
      levels of sex hormone-binding globulin (SHBG) significantly increased during
      treatment in comparison with baseline, whereas in the same time period no changes
      occurred in control women. These findings suggest that similar to the pill
      containing 30 microg EE2, the lower dosage of the EE2 pill (20 microg) is also
      capable of reducing bone resorption. Twenty and 30 microg EE2 pills exert the
      same biological estrogenic effect. In fact, SHBG levels significantly increased
      with both pills. However, an additional effect of the progestin compound that
      could act directly on progestin or estrogen receptors of bone cannot be excluded.
      Since contraception with a pill containing the lowest estrogen dose is associated
      with the lowest incidence of side effects, these findings further suggest a pill
      containing 20 microg EE2 for young post-adolescent women would be the best
      choice.

PMID- 10899482
TI  - Collagen metabolism markers as a reflection of bone and soft tissue turnover
      during the menstrual cycle and oral contraceptive use.
AB  - Two different groups of women, 23 healthy young adults and 13 women with chronic
      posterior pelvic pain, were studied before and during use of oral contraceptives
      (OC). Collagen metabolism markers-here, the amino-terminal propeptide of type I
      procollagen, the carboxy-terminal telopeptide of type I collagen, and the amino
      terminal of procollagen type III-as well as hormones and other endocrine factors
      indicating the balance between androgen expression/anabolism and catabolism of
      the subjects (testosterone, sex-hormone binding globulin, and insulin-like growth
      factor I were measured. Type I procollagen, the carboxy-terminal telopeptide of
      type I collagen, and the amino-terminal of procollagen type III were all
      significantly decreased during OC use. These findings implicate OC use-induced
      changes in collagen type I and III turnover. A shift in the anabolic/catabolic
      balance was also recorded indicating a less anabolic situation during OC use.

PMID- 10899483
TI  - In vitro assessment of the structural integrity of the female condom after
      multiple wash, dry, and re-lubrication cycles.
AB  - Since the introduction of the female condom in the early 90s, there have been
      numerous reports of reuse of the device. In response to these reports, studies
      were undertaken to evaluate the safety of female condom reuse. If reuse were
      shown to be safe, then programmatic costs of introduction of the female condom
      would be reduced allowing it to be more widely available. This article outlines
      the results of in vitro structural integrity testing of the female condom after
      multiple wash, dry, and re-lubrication cycles. Devices were tested up to 10
      washes using water leakage, burst, and tensile seam testing. All results were
      compared to the United States Food and Drug Administration (US FDA) standards for
      an unused female condom. The results of the structural integrity tests for all 6
      washing procedures examined in this study were above the FDA minimum standards
      for seam strength and burst tests. For the water leakage test, 3 of 6 washing
      procedures tested passed the required FDA minimum standards (no holes detected).
      From the results of the study, it seems that washing, drying, and re-lubricating
      the female condom up to 10 times leads to some deterioration in the structural
      integrity of the device for specified washing procedures. Further studies are
      currently being conducted to establish the safety of female condom reuse with
      respect to microbial retention, structural integrity after in vivo use, and viral
      permeability.

PMID- 10899484
TI  - Efficacy, acceptability, and clinical effects of a low-dose injectable
      contraceptive combination of dihydroxyprogesterone acetophenide and estradiol
      enanthate.
AB  - A total of 1,904 women, aged 15-38, used an injectable contraceptive combination
      of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate, given
      once during each menstrual cycle between the 7th and 10th day, and preferably on
      the 8th day of the cycle, for a total of 17,576 cycles. Of these 1,904 women,
      1,197 completed 12 cycles of use of the injectable combination. One subject
      became pregnant during the trial, resulting in a cumulative pregnancy rate of
      0.07%. Principal reasons for discontinuation were personal, non-medical reasons,
      such as lost to follow-up, no longer wished to continue, protocol violation,
      desire to change to another contraceptive method, moved away, or other personal
      reasons. Mean weight of 1,901 subjects at admission to the trial was 53.5 +/- 0.2
      kg and this increased to 54.3 +/- 0.3 kg after 12 cycles of use. Approximately
      50% of subjects experienced menstrual bleeding similar to normal throughout the
      study period. The most frequent menstrual abnormality was irregular bleeding,
      experienced by approximately one-third of subjects.

PMID- 10899485
TI  - DMPA use above the age of 35 in Thai women.
AB  - A prospective study of depot-medroxyprogesterone acetate (DMPA) use in women aged
      above 35 years was conducted in Bangkok, Thailand. The objectives of the study
      were to evaluate efficacy, continuation rate, and side effects of DMPA use in
      these women. A total of 60 women were enrolled in a one-year clinical trial.
      Their mean age was 38 years. Most of them had completed primary school. No
      accidental pregnancies occurred throughout the 1-year use in this study. The
      continuation rate was 20%. Irregular bleeding was the major cause of termination.
      The major side effect was also irregular bleeding. Nevertheless, DMPA in older
      women is a safe and effective contraceptive. DMPA is a contraceptive akterbatuve
      fir women aged above 35 with contraindications to combination oral
      contraceptives.

PMID- 10899486
TI  - Changes in menstrual and haematological indices among Norplant acceptors.
AB  - A longitudinal study of women using Norplant(R) was conducted to determine the
      effects of levonorgestrel implants on menstrual and haematological indices among
      the acceptors. Packed cell volume (PCV), white blood cell (WBC) concentrations
      (total and differential), and platelet concentration were performed at pre
      insertion and at the 12-month follow-up. Each acceptor received a menstrual
      calendar to chart all bleeding, and spotting events. The mean PCV was 40.5 +/- 2.
      4 at insertion and had a statistically significant (p <0.01) rise to a mean value
      of 42.2 +/- 2.6 at 12 months. The mean WBC concentration had a significant
      decrease at 12 months (p <0.001) when compared with the pre-insertion value.
      Similarly, the neutrophil and lymphocyte concentration had a statistically
      significant decrease (p <0.05 and p <0.01, respectively) at 12 months of use. The
      reduced values in the concentrations of monocytes, eosinophils and basophils did
      not reach significant levels. The mean value of the platelet concentrations had a
      significant decline at 12 months of use (p <0.001). Reduced bleeding patterns
      were more commonly reported compared to increased bleeding episodes. This pattern
      was associated with increased PCV, a change that may prevent anaemia in
      developing countries. The decline in the platelet concentration at 12 months of
      study was, however, a source of concern that will require follow-up.

PMID- 10899487
TI  - Provision of emergency contraceptive pills to spermicide users in ghana.
AB  - This study evaluated the effect of two approaches to provision of emergency
      contraceptive pills (ECPs) on ECP use and unprotected intercourse among women
      relying on spermicides for contraception. The study enrolled 211 women at 4
      family planning clinics in Ghana. At two clinics, participants were advised to
      return to the clinic within 3 days after unprotected intercourse to obtain ECPs.
      At the other two clinics, participants were given ECPs to take home for use if
      unprotected intercourse occurred. All participants were asked to maintain daily
      diaries for 8 weeks to record information on sexual activity, spermicide use, and
      ECP use. Women at all clinics used ECPs after at least 78% of unprotected coital
      acts. ECPs were used more promptly by women who had the pills at home. At three
      of the clinics, at most 1.3% of the coital acts were unprotected; at the fourth,
      6.7% were unprotected. Our data did not suggest that the availability of ECPs
      increased the frequency of unprotected intercourse.

PMID- 10899488
TI  - The human pluripotent stem cell: impact on medicine and society.
AB  - OBJECTIVE: To discuss the current state of the science surrounding human
      pluripotent stem cells and to show that the derivation of such cells from donated
      preimplantation human embryos should be eligible for federal funding provided
      that certain protections are met. DESIGN: A literature search focusing on the
      scientific aspects of pluripotent stem-cell research and analyses of current and
      past legislation and federal panel recommendations. CONCLUSION(S): The current
      federal laws regulating the permission necessary to obtain fetal tissue from
      elective pregnancy terminations are intended to insulate the decision to
      terminate a pregnancy from the potential positive influence of fetal tissue
      transplantation. A similar situation can be created for the derivation of cells
      from excess preimplantation human embryos produced by IVF programs. If, as in
      fetal tissue research, assurances can be made that the research will have no
      influence on the decision to dispose of the embryo, the derivation of pluripotent
      stem cells from embryo should proceed with federal funding.

PMID- 10899489
TI  - Fertility drugs and ovarian cancer: what are the practical implications of the
      ongoing debate?

PMID- 10899490
TI  - Effects of tibolone and continuous combined hormone replacement therapy on
      parameters in the clotting cascade: a multicenter, double-blind, randomized
      study.
AB  - OBJECTIVE: To determine the effects of tibolone and continuous combined HRT
      (ccHRT) on parameters in the clotting cascade. DESIGN: Randomized, double-blind
      study. SETTING: Hemostasis unit of a university hospital clinic in Germany.
      PATIENT(S): Sixty healthy postmenopausal women. INTERVENTION(S): Twenty-nine
      subjects were treated with tibolone (2.5 mg/d) and 31 with oral ccHRT containing
      estradiol (2 mg/d) + estriol (1 mg/d) + norethindrone acetate (1 mg/d). MAIN
      OUTCOME MEASURE(S): Effects on parameters in the clotting cascade at baseline and
      after 12 and 24 weeks of treatment. RESULT(S): Tibolone increased fibrinolysis
      parameters without significantly altering coagulation parameters. Treatment with
      ccHRT resulted in a stimulating effect on parameters of both fibrinolysis and
      coagulation. Tibolone showed a stronger reduction of factor VII activity; less
      reduction of AT-III, protein C activity, and protein S activity; stronger
      increase of the activated partial thromboplastin time, plasminogen and
      plasminogen-antiplasminogen complexes; and less increase of D-Dimer than ccHRT.
      Both preparations similarly reduced climacteric complaints, whereas tibolone
      showed less breast complaints than ccHRT. CONCLUSION(S): This study confirms that
      tibolone, and to a lesser extent also ccHRT, changes hemostasis parameters toward
      a more fibrinolytic profile, which may diminish the risk of venous thrombosis.

PMID- 10899491
TI  - Clonidine raises the sweating threshold in symptomatic but not in asymptomatic
      postmenopausal women.
AB  - OBJECTIVE: To determine the effects of clonidine, which reduces central
      sympathetic activation, on the sweating threshold in postmenopausal women with
      and without hot flashes. DESIGN: Laboratory physiologic study. SETTING:
      University medical center. PATIENT(S): 12 healthy postmenopausal women reporting
      frequent hot flashes and 7 reporting none. INTERVENTION(S): In two separate
      sessions, participants received a blind intravenous injection of clonidine HCl (2
      microg/kg of body weight) or placebo, followed by body heating. MAIN OUTCOME
      MEASURE(S): Core body temperature, mean skin temperature, sweat rate, sternal
      skin conductance level, and blood pressure. RESULT(S): Symptomatic women had
      significantly lower core body temperature sweating thresholds than asymptomatic
      women after receiving placebo. Clonidine significantly increased this threshold
      in symptomatic women but lowered it in asymptomatic women. CONCLUSION(S): These
      results support the hypothesis that elevated brain norepinephrine levels reduce
      the sweating threshold in symptomatic women, thereby contributing to the
      initiation of menopausal hot flashes.

PMID- 10899492
TI  - Efficacy of medroxyprogesterone treatment in infertile women with endometriosis:
      a prospective, randomized, placebo-controlled study.
AB  - OBJECTIVE: To determine the efficacy of medroxyprogesterone acetate (MPA), 50
      mg/d for 3 months, in treating endometriosis, with a follow-up of 6 months.
      DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING:
      Academic infertility unit in a teaching hospital. PATIENT(S): One hundred
      infertile women found to have endometriosis at laparoscopy, with 50 recruited to
      each treatment arm. INTERVENTION(S): Laparoscopy within 3 months of finishing
      therapy. MAIN OUTCOME MEASURE(S): Initial and second-look laparoscopy for revised
      American Fertility Society stages and scores, pregnancies achieved, effects on
      well-being via symptomatic improvement, and side effects. RESULT(S): Whether
      initially high or low, both MPA and placebo therapy achieved similar
      statistically significant reductions in stages and scores at second-look
      laparoscopy. MPA was rated more effective in improving overall well-being. Side
      effects were minimal in both groups (10% MPA; 2% placebo). Six pregnancies
      occurred without other endometriosis therapy being instituted in the placebo
      group (3 during therapy), and one with MPA (0 during therapy). CONCLUSION(S):
      Both MPA and placebo appear equally and significantly effective in treating
      endometriosis over a 3-month period, as judged by comparative laparoscopy.
      Therefore, not only must the use of MPA at 50 mg/d over 3 months be questioned,
      but the performance of placebo also suggests the need to review whether therapy
      should be instituted at all as well as the present concept that endometriosis is
      frequently a spontaneously progressive phenomenon.

PMID- 10899493
TI  - Impact of stage III-IV endometriosis on recipients of sibling oocytes: matched
      case-control study.
AB  - OBJECTIVE: To evaluate the impact of severe endometriosis on IVF-ET outcome in
      women receiving oocytes from the-same donor. DESIGN: A matched case-control
      study. SETTING: Oocyte donation program at the Instituto Valenciano de
      Infertilidad. PATIENT(S): Fifty-eight recipients were included in a matched case
      control study of IVF-ET in our oocyte donation program. Twenty-five patients were
      diagnosed by laparoscopy with stage III-IV endometriosis (group I), while the
      remaining 33 were free of the disease (group II). On the day of retrieval,
      oocytes from a single donor were donated to recipients from both groups. Some of
      the donors supplied oocytes for more than 2 patients. Recipients received steroid
      replacement therapy for endometrial preparation. INTERVENTION(S): Ovarian
      stimulation and oocyte retrieval in donors. Uterine embryo transfer (ET) in
      recipients after appropriate exogenous hormone replacement therapy (HRT). MAIN
      OUTCOME MEASURE(S): Pregnancy, implantation, miscarriage, and live birth rates.
      RESULT(S): The number of oocytes donated and fertilized, as well as the number of
      available and transferred embryos, was not statistically different between the
      two groups. Pregnancy, implantation, and miscarriage rates were not affected by
      stage III-IV endometriosis when compared with the control group. The live birth
      rate was 28.0% in the group with endometriosis and 27.2% in the control group.
      CONCLUSION(S): These results show that implantation is not affected by stage III
      IV endometriosis. Given the contemporary methods of endometrial preparation for
      transfer of embryos derived from donor oocytes, any potential negative effect of
      severe endometriosis on the uterine environment is undetectable.

PMID- 10899494
TI  - Secretion of inhibin B during ovarian stimulation is decreased in infertile women
      with endometriosis.
AB  - OBJECTIVE(S): To determine the levels and pattern of inhibin B secretion during
      ovarian stimulation in patients with endometriosis and to evaluate the
      correlation between inhibin B levels and variables of follicular and oocyte
      development. DESIGN: Retrospective cohort study. SETTING: IVF center. PATIENT(S):
      Women with endometriosis (n = 20) and tubal factor (n = 10) as the only cause of
      infertility. INTERVENTION(S): Inhibin B levels were measured during gonadotropin
      stimulation on day 1, days 8-11, day of hCG administration, and oocyte retrieval.
      MAIN OUTCOME MEASURE(S): Patterns and levels of inhibin B secretion were compared
      in the two groups. Other variables analyzed were age, days of gonadotropin
      stimulation and total ampules used, oocytes retrieved, and the fertilization and
      pregnancy rate. RESULT(S): Inhibin B levels and number of oocytes retrieved were
      significantly lower in patients with endometriosis than in the control group. Two
      patterns of inhibin B secretion were noted: It peaked in the midfollicular phase
      or on the day of hCG administration. In contrast, E2 levels peaked on the day of
      hCG administration. Inhibin B in the midfollicular phase in both groups
      correlated positively with number of oocytes retrieved. In addition, E2 and
      inhibin B levels in the midfollicular phase correlated positively. CONCLUSION(S):
      Decreased inhibin B secretion in patients with endometriosis suggests impaired
      granulosa cell function. Inhibin B may serve as an alternate marker to assess
      follicular development or to predict the number of oocytes retrieved.

PMID- 10899495
TI  - Effect of peritoneal fluid from women with endometriosis on implantation in the
      mouse model.
AB  - OBJECTIVE: To investigate the potential role of peritoneal fluid (PF) from women
      with or without endometriosis in implantation in mice with use of the delayed
      implantation model. DESIGN: A murine experimental model with markers of uterine
      receptivity and prospective comparison of the effects of human PF on
      implantation. SETTING: Academic university and hospital program. INTERVENTION(S):
      PF collected from women with and without endometriosis was injected
      intraperitoneally into recently mated mice. MAIN OUTCOME MEASURE(S): Implantation
      sites were counted in treated and untreated animals, and the alphavbeta3 integrin
      was measured in the pregnant mouse uterus by immunohistochemistry with in situ
      hybridization. Leukemia inhibitory factor and the beta3 subunit of alphavbeta3
      were measured by Northern blot during early pregnancy and after injections of PF.
      RESULT(S): Animals receiving PF from infertile women with endometriosis had a
      reduction in the number of implantation sites compared with animals that received
      PF from fertile women or from patients with recently treated endometriosis. In
      the mouse, expression of alphavbeta3 and leukemia inhibitory factor peaked at the
      time of implantation and was reduced by injections of human PF from infertile
      patients with endometriosis. CONCLUSION(S): Leukemia inhibitory factor and
      alphavbeta3 are coexpressed at the time of implantation in the mouse. PF from
      women with endometriosis has a detrimental effect on embryo implantation, perhaps
      by adversely affecting uterine receptivity.

PMID- 10899496
TI  - Polycystic ovaries in adolescents and the relationship with menstrual cycle
      patterns, luteinizing hormone, androgens, and insulin.
AB  - STUDY OBJECTIVE: To evaluate the possible role of inappropriate LH secretion,
      hyperandrogenism, and hyperinsulinemia in the development of polycystic ovaries
      (PCO) and the polycystic ovary syndrome. DESIGN: Observational. SETTING: General
      population samples. PARTICIPANTS: 58 adolescents with regular menstrual cycles,
      50 with irregular menstrual cycles, and 29 with oligomenorrhea (age 16.7+/-0.9
      years). INTERVENTIONS: Transabdominal pelvic ultrasonography and vena puncture.
      MAIN OUTCOME MEASURES: PCO; LH, androstenedione, and testosterone levels;
      overnight fasting insulin concentrations; and oligomenorrhea. RESULTS: The
      prevalence of PCO increased significantly with the irregularity of the menstrual
      cycle pattern, as illustrated by the study, finding PCO in 9% of the girls with
      regular menstrual cycles, 28% of those with irregular menstrual cycles, and 45%
      of oligomenorrheic girls. The LH and androgen concentrations were significantly
      higher in girls with PCO; the insulin levels and the glucose-insulin ratio did
      not differ when the girls with PCO were compared with girls with normal ovaries.
      Oligomenorrheic girls with PCO had the highest androgen and LH concentrations;
      their insulin concentrations and glucose-insulin ratio were in the same range as
      girls with regular menstrual cycles and normal ovaries; and both their hip and
      waist girths were wider, although their waist-hip ratio was normal. CONCLUSIONS:
      PCO in adolescents is associated with irregular menstrual cycles, oligomenorrhea,
      and/or high androgen and LH levels; but no relationship was found with the
      insulin level or glucose-insulin ratio. Thus, it is doubtful that
      hyperinsulinemia is an important factor in the development of PCO or polycystic
      ovary syndrome.

PMID- 10899497
TI  - Prevalence of 21-hydroxylase-deficient nonclassic adrenal hyperplasia and insulin
      resistance among hirsute women from Puerto Rico.
AB  - OBJECTIVE: To determine the prevalence of 21-hydroxylase (21-OH)-deficient
      nonclassic adrenal hyperplasia (NCAH) and insulin resistance in hirsute women
      from Puerto Rico. DESIGN: Cross-sectional prospective study. SETTING: Clinical
      research center. PATIENT(S): 100 consecutive untreated hirsute women. MAIN
      OUTCOME MEASURE(S): Fasting total T, free T, DHEAS, insulin, and glucose were
      measured, and a 60-minute acute ACTH-(1-24) stimulation for 17
      hydroxyprogesterone (17-HP) was performed. A diagnosis of 21-OH-deficient NCAH
      was considered when the stimulated 17-HP level was >30.3 nmol/L. The
      glucose/insulin ratio was calculated as a measure of insulin resistance (normal
      value, > or =4.5). RESULT(S): Patients had a mean (+/-SD) age of 26.8+/-6.6
      years; 82 were oligomenorrheic. Overall, 12%, 8%, and 60% of patients had
      elevated levels of DHEAS, total T, or free T, respectively. One patient was
      identified as having 21-OH-deficient NCAH. Eight women, none of whom had NCAH,
      were found to be hyperglycemic; four of these women had type 2 diabetes mellitus.
      Excluding hyperglycemic patients, a glucose/insulin ratio of <4.5, consistent
      with IR, was found in 51.7%. CONCLUSION(S): The prevalence of 21-OH-deficient
      NCAH among patients from Puerto Rico does not differ significantly from that
      reported for other non-Jewish, non-Hispanic white populations.

PMID- 10899498
TI  - Low serum estradiol concentrations after five days of controlled ovarian
      hyperstimulation for in vitro fertilization are associated with poor outcome.
AB  - OBJECTIVE: To evaluate the prognostic significance of low serum E2 concentrations
      in controlled ovarian hyperstimulation (COH) cycles for IVF. DESIGN:
      Retrospective study. SETTING: Assisted conception unit of a university hospital.
      PATIENT(S): One thousand four hundred and forty patients undergoing COH for IVF.
      INTERVENTION(S): COH, serum E2 measurement, ultrasonographic scanning of ovarian
      follicles, oocyte retrieval, and ET. MAIN OUTCOME MEASURE(S): Cancellation and
      pregnancy rates. RESULT(S): Patients were classified into four groups according
      to serum E2 levels on the sixth day of COH: group A (E2 level < 50 pg/mL [114
      cycles]), group B (E2 level 51-100 pg/mL [189 cycles]), group C (E2 level 101-200
      pg/mL [320 cycles]), and group D (E2 level >200 pg/mL [817 cycles]). Group A
      experienced the highest cancellation rates (65.1%) and lowest pregnancy rates
      (7.8%) despite requiring significantly more hMG ampules (47.8+/-1.7). The
      cancellation rate was higher (75.1%) and no pregnancy occurred in a subset of
      group A in whom COH was initiated with > or =3 ampules (225 IU) of gonadotropins.
      CONCLUSION(S): In COH cycles using luteal phase buserelin, low initial serum E2
      concentrations are associated with poor outcome.

PMID- 10899499
TI  - Coexistent hemoconcentration and hypoosmolality during superovulation and in
      severe ovarian hyperstimulation syndrome: a volume homeostasis paradox.
AB  - OBJECTIVE: To investigate the concomitant time courses of the changes in
      osmolality and calculated blood volume during the genesis of ovarian
      hyperstimulation syndrome (OHSS). DESIGN: Prospective longitudinal study.
      SETTING: IVF-ET program in a university-based assisted reproductive technology
      center. PATIENT(S): Thirty women undergoing superovulation for IVF-ET.
      INTERVENTION(S): Blood and urine samples were obtained on seven occasions from
      the start of FSH stimulation until a pregnancy test. Five women with severe OHSS
      had daily blood and urine tests during hospitalization. MAIN OUTCOME MEASURE(S):
      Changes in serum and urine osmolality, serum electrolytes, albumin, hemoglobin,
      and hematocrit. RESULT(S): Blood volume in women with OHSS decreased
      significantly by 20% from days hCG +2 to +4, followed by a sustained increase of
      30% above baseline from days hCG +8 to +12. There was no statistically
      significant change in blood volume in women without OHSS. There was a sharp
      decrease in serum osmolality in women without OHSS between days 0 and hCG +2,
      which recovered toward baseline from day 4 after hCG. In women with OHSS, there
      was an unexpected increase in osmolality of 6 mOsm/kg between days hCG -2 and 0,
      followed by a decrease of 8 mOsm/kg by day hCG +2; this was sustained until day
      hCG +12. Patients with OHSS demonstrated a concentration and dilution of their
      urine during the acute and recovery phases of the syndrome, respectively, despite
      persistence of the hypoosmolar state. CONCLUSION(S): Decreased osmolality in
      severe OHSS is maintained despite significant decreases and increases in blood
      volume, suggestive of fundamental alterations in osmoregulation.

PMID- 10899500
TI  - Subcutaneously administered Repronex in female patients undergoing in vitro
      fertilization is as effective and well tolerated as intramuscular menotropin
      treatment. Repronex SC, IVF Study Group.
AB  - OBJECTIVE: To determine the efficacy and safety of Repronex SC as compared with
      Repronex IM and Pergonal IM in patients undergoing IVF. DESIGN: Open-label,
      randomized, parallel-group, multicenter study. SETTING: Fifteen academic and
      private fertility clinics with IVF experience. PATIENT(S): Premenopausal women
      with regular ovulatory menstrual cycles undergoing IVF for infertility
      attributable to tubal factors, endometriosis (stage I or II), or unknown factors.
      INTERVENTION(S): Down-regulation with leuprolide acetate followed by up to 12
      days of treatments with gonadotropins, hCG administration, oocyte retrieval, and
      embryo transplant. MAIN OUTCOME MEASURE(S): Mean number of oocytes retrieved,
      chemical, clinical, and continuing pregnancies, incidence of oocyte retrieval and
      embryo transfer, and peak serum E2 concentrations. RESULT(S): There were no
      significant differences among the treatment groups except for a higher percentage
      of continuing pregnancies in the Repronex SC group. Gonadotropin therapy was well
      tolerated in all three treatment groups. The Repronex SC group had a
      significantly higher incidence of transient mild/moderate injection site
      reactions during the first few days of therapy. CONCLUSION(S): Repronex SC is
      comparable in therapeutic effectiveness and safety to Repronex IM and Pergonal IM
      in patients undergoing IVF and provides an alternative route of injection for
      self-administration of gonadotropin.

PMID- 10899501
TI  - Pregnancy rates after embryo transfer depend on the provider at embryo transfer.
AB  - OBJECTIVE: To evaluate the effect of individual providers on pregnancy outcome
      after embryo transfer. DESIGN: Retrospective data analysis. SETTING: University
      based tertiary-care assisted reproductive technology program with 10 physician
      providers. PATIENT(S): Six hundred and seventeen women who underwent 854 fresh
      embryo transfers between January 1996 and January 1999. INTERVENTION(S):
      Pregnancies after embryo transfer were recorded for each provider. MAIN OUTCOME
      MEASURE(S): Establishment of a clinical pregnancy. RESULT(S): Three hundred
      ninety-three clinical pregnancies resulted from 854 embryo transfers, for an
      overall clinical pregnancy rate of 46.0% per embryo transfer. Three hundred forty
      seven (40.6%) pregnancies were ongoing. The clinical pregnancy rate varied
      significantly between providers: for example, 17.0% (47 transfers) vs. 54.3% (57
      transfers) (P<.05). Similarly, the ratio of high-grade embryos required to
      produce a gestational sac differed between providers. The number or quality of
      embryos transferred did not differ significantly. CONCLUSION(S): Significant
      differences were observed in pregnancy rates after embryo transfer done by
      different providers, suggesting that embryo transfer technique may influence
      pregnancy outcome in assisted reproductive technology.

PMID- 10899502
TI  - Development of brief stress management support groups for couples undergoing in
      vitro fertilization treatment.
AB  - OBJECTIVE: To develop and assess the efficacy of couples stress management groups
      offered concurrently with IVF treatment. DESIGN: Couples in IVF treatment were
      given the option of participating in a biweekly stress management group. SETTING:
      The IVF treatment clinic at Wilford Hall Medical Center, San Antonio, Texas.
      PATIENT(S): One or both members of 17 couples participated in the program in one
      of four group cycles. INTERVENTION(S): A cognitive behavioral treatment model was
      used to help couples process their feelings and cognitions about the impact of
      infertility on their life and explore their expectations about their future
      options for becoming parents. MAIN OUTCOME MEASURE(S): Couples were asked to
      anonymously evaluate the efficacy of the group after they had completed their IVF
      cycle. RESULT(S): Participants reported that the group helped them deal with the
      stress of infertility and that they valued the social bonds they formed with
      other group members. CONCLUSION(S): These data suggest that brief focused group
      therapy, offered while couples are undergoing IVF, is an effective way to help
      people deal with the stress of infertility treatment.

PMID- 10899503
TI  - Increased frequency of chromosomal abnormalities in female partners of couples
      undergoing in vitro fertilization or intracytoplasmic sperm injection.
AB  - OBJECTIVE: To determine the prevalence of chromosomal abnormalities in female
      partners of couples undergoing IVF or intracytoplasmic sperm injection (ICSI).
      DESIGN: Prospective study. SETTING: Leuven University Fertility Center.
      PATIENT(S): Female candidates for IVF or ICSI. INTERVENTION(S): An initial
      cytogenetic study was performed on peripheral blood lymphocyte cultures using G-
      and R-banding. In all patients, > or =25 metaphases were examined. If a
      chromosomal aberration was detected, additional cytogenetic studies were
      performed for precise identification. MAIN OUTCOME MEASURE(S): Abnormal female
      karyotypes in comparison with the general female population. RESULT(S):
      Cytogenetic analysis was performed in 263 female partners of couples before
      entering an IVF or ICSI program. The prevalence of autosomal reciprocal balanced
      translocations was seven times higher in the study group (1.14%) than in the
      general population (0.16%). All abnormal karyotypes were found in the IVF group
      with male factor infertility. CONCLUSION(S): Chromosomal abnormalities are more
      frequent in the female partners of couples seeking fertility treatment. We
      recommend chromosomal analysis in women before starting IVF or ICSI treatment,
      even in the presence of male factor infertility.

PMID- 10899504
TI  - Predictive value of basal follicle-stimulating hormone concentrations in a
      general subfertility population.
AB  - OBJECTIVE: To assess the predictive value of elevated basal FSH concentrations
      during the initial subfertility workup with respect to fecundity in a general
      subfertility population with ovulatory menstrual cycles. DESIGN: Nested case
      control study. SETTING: Fertility center of a university hospital. PATIENT(S):
      Fifty subfertile women with basal FSH levels >10.0 IU/L and 50 age-matched
      controls. INTERVENTION(S): Long-term follow-up (3-7 years). MAIN OUTCOME
      MEASURE(S): Pregnancies, deliveries, and time to pregnancy. RESULT(S): Patients
      with elevated basal FSH levels and controls were comparable with regard to basic
      characteristics, clinical diagnoses, and subfertility treatment. Long-term follow
      up showed that 52% of the women with elevated basal FSH concentrations became
      pregnant (positive predictive value 48%) versus 62% of the controls, and 42%
      versus 46% eventually delivered a child, respectively. The mean time to pregnancy
      was 3.0 years in the elevated-FSH group and 3.4 years in controls. Most of the
      pregnancies in both groups occurred after spontaneous conceptions. CONCLUSION(S):
      The results of this study suggest that screening for elevated basal FSH
      concentrations is of no additional value in a general subfertility population
      with ovulatory menstrual cycles.

PMID- 10899505
TI  - Successful pregnancy after 24 consecutive fetal losses: lessons learned from
      surrogacy.
AB  - OBJECTIVE: To offer surrogacy as a treatment option to patients in whom maternal
      rather than fetal factors are responsible for high-order unexplained habitual
      abortions. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 36
      year-old woman with 24 consecutive abortions over 11 years. INTERVENTION(S): A
      regular IVF procedure in the aborting woman and transfer of two good-quality
      embryos to the surrogate mother, who had previously received hormones. MAIN
      OUTCOME MEASURE(S): Ovarian response, oocytes, fertilization, and embryo quality
      in the aborting patient. Endometrial thickness, implantation, pregnancy, and
      delivery in the surrogate mother. RESULT(S): Transfer of two embryos to the
      surrogate mother led to a clinical pregnancy, which was uneventful until term.
      Cesarean section was performed for breech presentation, with delivery of a
      healthy male. CONCLUSION(S): Surrogacy can be offered as a treatment option to
      patients in whom maternal rather than fetal factors are responsible for high
      order unexplained habitual abortions.

PMID- 10899506
TI  - Neutrophils infiltrating the endometrium express vascular endothelial growth
      factor: potential role in endometrial angiogenesis.
AB  - OBJECTIVE(S): To identify leukocytes within the human endometrium expressing
      vascular endothelial growth factor (VEGF). DESIGN(S): Prospective cohort study.
      SETTING(S): Healthy volunteers in an academic research environment. PATIENTS(S):
      Twenty-one normal cycling women without abnormal menstrual bleeding or
      infertility. INTERVENTION(S): Endometrial tissue collection by Pipelle de Cornier
      aspiration. MAIN OUTCOME MEASURES(S): Histologic, immunohistochemical (CD3, CD34,
      CD56, CD68, neutrophil elastase, estrogen and P receptors, VEGF), and
      simultaneous double immunoenzymatic labeling analysis of VEGF-positive cells
      within the human endometrium. RESULT(S): Ten endometrial samples were obtained in
      the proliferative (cycle days 5-10) and 11 samples in the secretory phase (cycle
      days 15-26). Immunohistochemical analyses showed the expected distribution of the
      different leukocyte cell types. Besides epithelial and stromal endometrial cells,
      the predominant cells that stained for VEGF were neutrophil granulocytes.
      Neutrophils were more abundant in the secretory phase but they expressed neither
      estrogen-a nor P receptors. CONCLUSION(S): Neutrophil granulocytes infiltrating
      the human endometrium express VEGF and regulate cyclical endometrial vascular
      proliferation. Ovarian steroids indirectly influence neutrophil migration.

PMID- 10899507
TI  - Expression of transforming growth factor-alpha, epidermal growth factor, and
      epidermal growth factor receptor in follicles of human ovarian tissue before and
      after cryopreservation.
AB  - OBJECTIVE: To study the expression of transforming growth factor-alpha (TGF
      alpha), epidermal growth factor (EGF), and EGF receptor in follicles of human
      ovarian tissue. DESIGN: A retrospective, controlled comparative study. SETTING:
      In vitro fertilization laboratory of a university hospital. PATIENT(S): Fifteen
      women with regular menstrual cycles who underwent laparoscopy and the biopsy of
      ovarian tissue. INTERVENTION(S): Paraffin sections were prepared from ovarian
      tissues, followed by immunohistochemical staining of TGF-alpha, EGF, and EGF
      receptor. MAIN OUTCOME MEASURE(S): Immunostaining for TGF-alpha, EGF, and EGF
      receptor in follicles of fresh and frozen ovarian tissues. RESULT(S):
      Immunoreactivities for TGF-alpha and EGF receptor were observed simultaneously in
      the oocytes of primordial, primary, preantral, and antral follicles. Strong
      staining for TGF-alpha and EGF receptor was present in thecal cells. The TGF
      alpha and EGF receptor was also expressed in some granulosa cells of primary to
      antral follicles. The EGF only stained weakly in the oocytes of primordial and
      primary follicles and in thecal cells. There was no difference in staining
      patterns for TGF-alpha, EGF, and EGF receptor between fresh and frozen ovarian
      tissues. CONCLUSION(S): The TGF-alpha and EGF receptor was expressed in
      primordial to antral follicles, indicating a role of TGF-alpha in regulating
      follicular development through binding to the EGF receptor. Freeze-thawing did
      not substantially alter immunoreactivites for TGF-alpha, EGF, and EGF receptor in
      frozen ovarian tissue.

PMID- 10899508
TI  - Histologic and ultrastructural evaluation of fresh and frozen-thawed human
      ovarian xenografts in nude mice.
AB  - OBJECTIVE: To compare histologic and ultrastructural characteristics of fresh and
      frozen-thawed human ovarian cortical tissue grafted into nude mice. DESIGN:
      Experimental prospective study. SETTING: An academic research environment.
      PATIENT(S): Ovarian biopsy specimens were obtained from 13 women undergoing
      laparoscopy for tubal ligation or infertility. ANIMAL(S): Forty nude mice.
      INTERVENTION(S): A minilaparotomy was performed to place fresh and frozen-thawed
      ovarian grafts subcutaneously (sc) or intraperitoneally (ip). Removal of the
      ovarian grafts was performed at 24 days. MAIN OUTCOME MEASURE(S): [1] the
      follicular population, [2] fibrosis, [3] vascularization of the grafted tissue,
      and [4] ultrastructural evaluation. RESULT(S): A greater fibrosis relative
      surface area was noted in frozen-thawed transplanted tissue than in fresh
      transplants. Regardless of this fibrosis, a similar follicular density was
      observed in fresh and frozen-thawed ovarian tissue 24 days after transplantation.
      Active angiogenesis was proved by both immunohistochemical study of the vascular
      endothelial growth factor and morphometric study of the vascular network. Normal
      ultrastructural characteristics were noted in frozen-thawed ovarian biopsies.
      CONCLUSION(S): Angiogenesis allows implantation of the graft even if it has been
      cryopreserved and thawed similarly to implantation of fresh tissue. The greater
      fibrosis observed in grafts after cryopreservation and implantation does not seem
      to affect the primordial and primary ovocyte population and their ultrastructural
      characteristics, but further studies must be conducted to prove that after
      cryopreservation and transplantation, ovocytes may achieve full maturation and
      fertilization.

PMID- 10899509
TI  - Endometrial glycodelin-A expression in the luteal phase of stimulated ovarian
      cycles.
AB  - OBJECTIVE: To determine if controlled ovarian hyperstimulation (COH) affects the
      endometrial expression of glycodelin-A (GdA). DESIGN: Prospective, controlled
      study. SETTING: Tertiary infertility clinic. PATIENT(S): Fifteen oocyte donors
      undergoing COH cycles and 19 natural-cycle control patients. INTERVENTION(S):
      COH, endometrial biopsies. MAIN OUTCOME MEASURE(S): Immunohistochemical scoring
      of endometrial GdA expression, morphologic endometrial dating, and serum E2, LH,
      and P4 concentrations. RESULT(S): GdA was detected in all subjects throughout the
      implantation window period. Immunolocalization was demonstrated in the
      endometrial glands and not in the stroma or on the surface. A significantly
      increased proportion of GdA-staining endometrial cells were noted in COH cycle
      patients as compared with natural-cycling control patients throughout the window
      of embryo implantation. Both cycle types demonstrated increasing GdA expression
      throughout the late luteal phase. A significant positive correlation was noted
      between GdA expression and serum E2 levels (r = 0.5, P<.001) in natural cycles
      and advanced histology in COH cycles (r = 0.63, P=.01). Neither LH nor P4 were
      correlated with endometrial GdA expression. CONCLUSION(S): COH cycles have a
      significantly increased endometrial GdA expression throughout the implantation
      phase of the luteal cycle when compared with normal menstrual cycles. The
      increased expression may affect implantation during COH cycles.

PMID- 10899510
TI  - Local effects of mifepristone on the nonhuman primate endometrium.
AB  - OBJECTIVE: To determine the effects of a low-dose mifepristone regimen on
      endometrium in the rhesus monkey by endometrial staging and analysis of molecular
      markers of endometrial receptivity. DESIGN: A prospective, randomized comparative
      study. SETTING: Academic research environment. ANIMAL(S): Normally cycling rhesus
      (Macaca mulatta) monkeys. INTERVENTION(S): Monkeys (5 per control or treatment
      group) received 0.03 mg of mifepristone in vehicle (sesame oil) per kilogram of
      body weight or vehicle daily from day 2 of the menstrual cycle to 7 days after
      the midcycle E2 surge. MAIN OUTCOME MEASURE(S): Serum estradiol (E2) and
      progesterone (P) levels; endometrial staging and immunoreactivity of leukemia
      inhibitory factor and interleukin-6 performed on fixed endometrial tissues; and
      relative abundance of endometrial estrogen and P receptor mRNA evaluated with
      semiquantitative reverse transcriptase polymerase chain reaction in which
      cyclophilin mRNA, a housekeeping gene product, was coamplified as the reference
      standard. RESULT(S): Mifepristone at 0.03 mg/kg/d induced a delay in the
      endometrial cycle with a shift from the late to midsecretory phase. This
      treatment regimen did not suppress the midcycle gonadotropin surge or,
      presumably, ovulation because P levels were normal during the midluteal phase.
      The staining intensity of leukemia inhibitory factor and interleukin-6 was
      dependent upon the endometrial stage and was decreased in treated monkeys. E and
      P receptor mRNAs increased significantly with mifepristone treatment compared
      with controls, another indication of delayed uterine staging. CONCLUSION(S):
      Mifepristone at 0.03 mg/kg/d had no antiovulatory effect but delayed development
      of the endometrium from the late to midsecretory phase. This study provides
      further evidence that endometrial maturation can be altered without affecting
      ovarian cyclicity.

PMID- 10899511
TI  - Expression of adrenomedullin in the human corpus luteum.
AB  - OBJECTIVE: Adrenomedullin (AM) is a potent hypotensive peptide found in human
      pheochromocytoma tissue. In the present study, the expression of AM mRNA in the
      human ovary was examined. DESIGN: Ovarian mRNA was analyzed in the follicle, the
      corpus luteum of mid-luteal phase, and early pregnancy. SETTING: Gunma University
      School of Medicine, Gunma, Japan. PATIENT(S): Premenopausal women with
      histologically normal ovary who were undergoing salpingoophorectomy.
      INTERVENTION(S): The dominant follicle and corpora lutea were isolated and total
      RNA was extracted from these tissues. MAIN OUTCOME MEASURE(S): Northern blot
      analysis of AM, receptor activity-modifying protein 2 (RAMP2), and LH/hCG
      receptor mRNA in human samples. RESULT(S): An AM mRNA transcript of 1.6 kilobases
      (kb) was detected in corpus luteum tissue; this transcript was identical to that
      which has been detected in placenta and fetal membrane. The AM and LH/hCG
      receptor mRNA levels were low in the mature follicle but increased in the corpus
      luteum of the mid-luteal phase and were maintained during early pregnancy. A
      single transcript of 0.8 kb for RAMP2 was also seen in the follicle and corpus
      luteum, the level of RAMP2 mRNA was relatively high in the preovulatory follicle
      and RAMP2 was present in the corpus luteum. CONCLUSION(S): The expression of AM,
      its receptor, and LH/hCG receptor may be an important component in the process of
      development and differentiation of the corpus luteum.

PMID- 10899512
TI  - The antiadhesive agent sodium hyaluronate increases the proliferation rate of
      human peritoneal mesothelial cells.
AB  - OBJECTIVE: Evaluating the influence of sodium hyaluronate on the proliferation
      rate of attached and nonattached human peritoneal mesothelial cells to elucidate
      whether this is a possible mechanism of action in peritoneal tissue repair.
      DESIGN: Controlled laboratory experiment. SETTING: A university hospital.
      PATIENT(S): Five patients undergoing colorectal surgery for noninfectious
      reasons. INTERVENTION(S): Human peritoneal mesothelial cells were harvested from
      patients undergoing a laparotomy for noninfectious reasons. Cells, both
      nonattached and attached, were incubated for 4 and 24 hours with different
      concentrations of sodium hyaluronate. Thereafter, the cell proliferation rate was
      measured by XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-car
      boxanilide) colorimetric assay. To mimic peritoneal injury, the cells were
      exposed to tumor necrosis factor alpha and/or lipopolysaccharide and were
      incubated immediately or after 24 hours of exposure to 0% or 0.2% sodium
      hyaluronate. Afterward, the cell proliferation rate was measured. MAIN OUTCOME
      MEASURE(S): Proliferation rate measured by XTT assay. RESULT(S): Sodium
      hyaluronate significantly increased the proliferation rate of mesothelial cells,
      both in a nonattached (P<.005) and attached (P<.001) state. Exposure of the
      mesothelial cells to tumor necrosis factor alpha and/or lipopolysaccharide
      diminished the cells' proliferation rate. However, incubation of these exposed
      cells with 0.2% sodium hyaluronate significantly increased the proliferation
      rate, regardless of whether the sodium hyaluronate was added immediately (P<.001)
      or after 24 hours (P<.001). CONCLUSION(S): Sodium hyaluronate increases the
      proliferation rate of human peritoneal mesothelial cells, both attached and
      nonattached, under normal conditions and after stimulation with tumor necrosis
      factor alpha and/or lipopolysaccharide.

PMID- 10899513
TI  - Detection of Chlamydia trachomatis DNA in archival paraffinized specimens from
      chronic salpingitis cases using the polymerase chain reaction.
AB  - OBJECTIVE: To identify Chlamydia trachomatis by the polymerase chain reaction
      (PCR) in fallopian tube tissues with chronic salpingitis. DESIGN: Retrospective
      case-control study. SETTING: Academic tertiary institution. PATIENT(S): Women
      with a pathological diagnosis of chronic salpingitis or normal fallopian tube
      hospitalized between September 1992 and November 1994. Initial identification of
      248 specimens with final analysis of 154. INTERVENTION(S): Paraffin-embedded
      fallopian tube tissues were analyzed with use of PCR to detect C. trachomatis.
      MAIN OUTCOME MEASURE(S): Identification of C. trachomatis DNA; demographics of
      age, ethnicity, parity, history of sexually transmitted disease, and surgical
      procedure. RESULT(S): C. trachomatis DNA was detected in 9 of 77 chronic
      salpingitis cases. Seventy-seven controls were negative for C. trachomatis. No
      statistically significant difference in age or ethnicity between cases and
      controls was identified. Nulliparity was more frequent in cases (26 of 74) than
      controls (14 of 76). Sexually transmitted disease history was more prevalent in
      cases (24 of 74) than controls (6 of 76). Chlamydia infection was not associated
      with a particular surgical indication. CONCLUSION(S): Chronic salpingitis is
      highly associated with the presence of C. trachomatis infection as detected by
      PCR.

PMID- 10899514
TI  - DNA ploidy of human granulosa cells from natural and stimulated in vitro
      fertilization cycles.
AB  - OBJECTIVE: To analyze and compare the DNA ploidy of granulosa cells from natural
      and gonadotropin-stimulated follicles obtained during IVF. DESIGN: Retrospective
      analysis of laboratory data. SETTING: University medical center. PATIENT(S):
      Seventy-three aspirates of dominant follicles from natural IVF cycles and 113
      aspirates from gonadotropin-stimulated cycles were analyzed. INTERVENTION(S):
      Cytospins were prepared and stained by the Feulgen-thionine method. MAIN OUTCOME
      MEASURE(S): Image DNA analysis was performed on an automated high-resolution
      image cytometer. DNA content and the number of nuclei with DNA content >5c were
      measured. RESULT(S): All samples from natural and gonadotropin-stimulated
      follicles were found to be diploid. Single cells with DNA content >5c were found
      in follicular fluid samples of four women with natural IVF cycles and in samples
      of nine women with gonadotropin-stimulated cycles. CONCLUSION(S): DNA ploidy of
      granulosa cells from natural follicles has not been studied before. In natural
      samples, granulosa cells were only diploid, without euploid polyploidization. We
      were unable to confirm DNA aneuploidy of granulosa cells in gonadotropin
      stimulated follicles of women undergoing IVF.

PMID- 10899515
TI  - Transfer of nonassisted hatched and hatching human blastocysts after in vitro
      fertilization.
AB  - OBJECTIVE: To determine the feasibility of performing blastocyst transfer 6 days
      after oocyte insemination. DESIGN: Retrospective clinical study. SETTING:
      University-based IVF center. PATIENT(S): All cases of IVF over a 1-year span of
      time (June 1998-1999) in which seven 2PN embryos were available for transfer.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and
      multiple pregnancy rates. RESULT(S): Transfer of blastocysts on days 5 and 6
      resulted in implantation rates of 69% and 33% (P=0.0006), clinical pregnancy
      rates of 89% and 59% (P=0.05), and multiple pregnancy rates of 39% and 10%
      (P=0.03), respectively. In cases in which blastocysts were spontaneously hatching
      or hatched on day 6 (9% of embryos), implantation and pregnancy rates were 52%
      and 80%, respectively. Embryos were successfully frozen in the hatched or
      hatching state with resultant clinical pregnancies. CONCLUSION(S): Transfer of
      embryos can be delayed to day 6 after oocyte insemination at which time a small
      percentage of embryos will hatch. Hatching of embryos by day 6 is a favorable
      prognostic factor for IVF outcome. Embryos that fail to hatch by day 6 may have a
      lower implantation potential. Difficulty with hatching embryos sticking to the
      transfer catheter was not encountered. Furthermore, hatching and hatched embryos
      can be frozen and with subsequent transfer result in pregnancies.

PMID- 10899516
TI  - Ovarian stimulation in in vitro fertilization with or without the "long"
      gonadotropin-releasing hormone agonist protocol: effect on cycle duration and
      outcome.
AB  - OBJECTIVE: To study the correlation between stimulation duration of IVF cycles,
      with and without GnRH agonist (GnRH-a), and cycle outcome. DESIGN: Retrospective
      analysis of data. SETTING: University-affiliated IVF clinic. PATIENT(S): 998 IVF
      cycles in which long GnRH-a protocol was used, and 155 cycles with hMG only.
      INTERVENTION(S): IVF cycles. MAIN OUTCOME MEASURE(S): Cycle outcome in number of
      oocytes and embryos, and pregnancy rate. RESULT(S): The mean stimulation duration
      (+/-SD) was 9.6+/-1.7 and 6.7+/-1.0 for the GnRH-a and the hMG-only cycles,
      respectively (P<0.01). In the GnRH-a group, no statistically significant
      correlation between cycle duration and pregnancy rate was found. Interestingly,
      the patients treated for 9 days had the highest number of oocytes retrieved and
      the highest pregnancy rate. Stimulation duration was not affected by age in
      either protocol. GnRH-a cycles yielded a significantly higher number of oocytes
      and embryos compared to cycles without GnRH-a. The pregnancy rate was similar in
      both groups. CONCLUSION(S): Stimulation duration in the long GnRH-a protocol
      group was significantly longer than in the hMG-only group. Stimulation duration
      was not affected by age. No statistically significant correlation was found
      between stimulation duration and cycle outcome in the long protocol group.

PMID- 10899517
TI  - Cancer risk among women sterilized with transcervical quinacrine in Chile: an
      update through 1996.
AB  - OBJECTIVE: To determine whether further follow-up of a cohort of Chilean women
      would demonstrate an increased risk of invasive cancer associated with quinacrine
      sterilization. DESIGN: Cohort study. Cancer cases were evaluated using cohort
      analyses. SETTING: Santiago and Valdivia, Chile. SUBJECT(S): Fourteen hundred
      ninety-two women who received transcervical quinacrine pellets for contraceptive
      sterilization between 1977 and 1989. METHOD(S): Interviews and reviews of medical
      records. MAIN OUTCOME MEASURE(S): Age- and site-specific incidence of invasive
      cancers. RESULT(S): During 13,444 person-years of follow-up, 25 invasive cancers
      were identified, including 8 new cases. This compares with 21.9 expected cancers,
      based on age-specific rates from the Cali, Colombia, cancer registry. Eight cases
      of cervical cancer were observed, compared with the 6.3 expected. Since the
      initial study's confirmation of a single case of leiomyosarcoma, no other
      noncervical uterine cancers have been diagnosed. The number of observed person
      years gives an expectation of 0.62 noncervical uterine cancers. One case of
      ovarian cancer was diagnosed, compared with the 0.99 expected. CONCLUSION(S):
      Rates of cancer among women exposed to intrauterine quinacrine are not
      significantly different from population-based rates.

PMID- 10899518
TI  - No differences in outcome of surgical sperm retrieval with intracytoplasmic sperm
      injection at different intervals after vasectomy.

PMID- 10899519
TI  - Pregnancy and delivery of healthy infants developed from vitrified oocytes in a
      stimulated in vitro fertilization-embryo transfer program.

PMID- 10899520
TI  - Hamartoma in a pubertal patient with complete androgen insensitivity syndrome and
      R(831)X mutation of the androgen receptor gene.

PMID- 10899521
TI  - Prostatic massage as a method for obtaining spermatozoa in men with psychogenic
      anejaculation.

PMID- 10899523
TI  - Range expansion of the tick Amblyomma triguttatum triguttatum, an australian
      vector of Q fever.
AB  - The tick Amblyomma triguttatum triguttatum has previously been reported from
      Western Australia, Queensland and New South Wales. A viable population of this
      species, including all developmental stages, has now been discovered on the
      southern end of Yorke Peninsula, South Australia. Species determination was
      carried out morphologically and using 18S and 16S rRNA. The data for 16S rRNA are
      the first published for this species. Amblyomma t. triguttatum is significant
      through its involvement in the natural, Australian cycle of Coxiella burnetti,
      the pathogen causing Q fever. The environment of Yorke Peninsula contains all of
      the components required for a natural Q fever cycle and three cases of this
      disease have been reported from this area since 1995. These findings reinforce
      the need to put in place effective mechanisms to monitor parasite distributions
      at a time of large scale global change.

PMID- 10899524
TI  - Microsporidia: emerging advances in understanding the basic biology of these
      unique organisms.
AB  - Microsporidia are long-known parasites of a wide variety of invertebrate and
      vertebrate hosts. The emergence of these obligate intracellular organisms as
      important opportunistic pathogens during the AIDS pandemic and the discovery of
      new species in humans renewed interest in this unique group of organisms. This
      review summarises recent advances in the field of molecular biology of
      microsporidia which (i) contributed to the understanding of the natural origin of
      human-infecting microsporidia, (ii) revealed unique genetic features of their
      dramatically reduced genome and (iii) resulted in the correction of their
      phylogenetic placement among eukaryotes from primitive protozoans to highly
      evolved organisms related to fungi. Microsporidia might serve as new
      intracellular model organisms in the future given that gene transfer systems will
      be developed.

PMID- 10899525
TI  - Vitellocytes and vitellogenesis in cestodes in relation to embryonic development,
      egg production and life cycle.
AB  - Vitellocytes have two important functions in cestode embryogenesis: (1) formation
      of hard egg-shell (e.g. Pseudophyllidea) or a delicate capsule (e.g.
      Cyclophyllidea), and (2) supplying nutritive reserves for the developing embryos.
      During evolution any of these two functions can be reduced or intensified in
      different taxa depending on the type of their embryonic development, degree of
      ovoviviparity and life cycles. Within the Cestoda, there are three monozoic taxa
      with only one set of genital organs: Amphilinidea, Gyrocotylidea and
      Caryophyllidea. In these monozoic taxa and some polyzoic groups with well
      developed vitellaria (e.g. Pseudophyllidea, Trypanorhyncha) a single oocyte
      [=germocyte] and a large number of vitellocytes (up to 30) are enclosed within a
      thick, hardened egg-shell, forming a type of eggs typical for the basic pattern
      of Neodermata. Only one type of egg-shell enclosures, the so-called
      'heterogeneous shell-globule vesicle' is common for the above mentioned cestode
      taxa. Each membrane-bounded vesicle of mature vitellocytes contains numerous
      electron-dense shell globules embedded in a translucent matrix. In free-living
      Neoophora and Monogenea there are two types of vesicles with dense granules; the
      second is considered to be proteinaceous reserve material. Within the Cestoda,
      the numbers of vitellocytes per germocyte are reduced in those taxa forming eggs
      of the 'Cyclophyllidean-type' (e.g. Cyclophyllidea, Tetraphyllidea,
      Pseudophyllidea). This is particularly evident in Cyclophyllidea; for example, in
      vitellocytes of Hymenolepis diminuta (Hymenolepididae) there are numerous
      vitelline granules of homogeneously electron-dense material; in Catenotaenia
      pusilla (Catenotaeniidae) there are three large, homogenous vitelline vesicles,
      while in Inermicapsifer madagascariensis (Anoplocephalidae) there is only one
      large vitelline vesicle, containing homogeneously electron-dense material, which
      occupies most of the vitelline cell volume. In this respect the Tetraphyllidea
      and Proteocephalidea, in forming eggs that lack a hard egg-shell, hold an
      intermediate position. A comparison of interrelationships which exist among types
      of vitellocytes, vitellogenesis, types of embryonic development, ovoviviparity
      and life cycles indicates parallelisms and analogies in adaptation to the
      parasitic way of life in different groups of cestodes. Knowledge on cestode
      vitellogenesis may also have an important applied aspect. Vitellocytes, due to
      their high metabolic rate, represent a very sensitive target for analysing effect
      of anthelminthic drugs upon the egg formation (ovicidal effects); rapid
      degeneration of vitellocytes is usually accompanied by a cessation of egg
      production.

PMID- 10899526
TI  - Fatty acid patterns of different stages of Oesophagostomum dentatum and
      Oesophagostomum quadrispinulatum as revealed by gas chromatography.
AB  - Total methylated fatty acid patterns of various developmental stages (third-stage
      larvae (L3), L3 and fourth-stage larvae (L4) cultured in vitro, L4 and female and
      male adults derived from intestinal contents) of the porcine nodular worms
      Oesophagostomum dentatum and Oesophagostomum quadrispinulatum and their
      cultivation medium were analysed by gas chromatography using Microbial
      Identification computer software. Fatty acids ranging from C-12 to C-20 could be
      separated. For each stage and species, characteristic patterns were found. The
      most prevalent fatty acids were C-18. The freshly exsheathed larvae contained the
      greatest variety of fatty acids (including short-chain fatty acids C-12 to C-15)
      with approximately equal amounts of fatty acids with odd and even chain lengths,
      whereas more advanced stages consisted of a lower number of fatty acids with
      mostly even chain lengths >/=C-16. Intestinal stages contained less odd-numbered
      fatty acids and less branched fatty acids than others. In contrast to intestinal
      L4, cultivated L4 had high amounts of C-15:0 and C-17:0. Sheathed L3 contained
      more C-18 than freshly exsheathed ones, and medium incubated for 7 days in the
      presence of parasites contained C-13 to C-15 and monounsaturated C-16, but less C
      18 and C-20:4 than fresh medium or medium incubated without worms. Based on the
      evaluation of stage- and species-specific fatty acid patterns random samples
      could be assigned to the correct stage and species. In a dendrogram based on
      fatty acid patterns the same stages of the two species formed the closest
      relationships, and the intestinal stages formed a clade distinct from the
      cultivated larvae and L3. All stages contained considerable relative amounts of
      arachidonic acid, the main precursor of eicosanoids. The fixed differences
      between species and stages indicate genetic regulation of fatty acid patterns,
      while environmental influences are mirrored by differences between cultivated and
      intestinal stages. Regulation of fatty acid patterns probably plays a role in
      worm physiology and host-parasite interaction.

PMID- 10899527
TI  - In vitro shock response to different stressors in free living and pathogenic
      Acanthamoeba.
AB  - Three stresses, viz heat, oxidative and pH shocks, were applied to cultures of
      three species of Acanthamoeba, free-living Acanthamoeba rhysodes and pathogenic
      Acanthamoeba castellanii and Acanthamoeba culbertsoni. The effect of each
      stressor on trophozoite integrity was evaluated by the amount of heat shock
      protein (HSP)60 and HSP70 produced and by exclusion of 0.2% Congo Red. HSP60 and
      HSP70 levels were estimated using Western blotting and subsequent densitometric
      analyses. Unstimulated trophozoites from A. rhysodes produced the lowest
      background levels of HSP60 and HSP70 and were the amoebae most affected by
      (mammalian-type) stresses as judged by their enhanced HSP production and
      decreased viability upon exposure to such conditions. In contrast, unstimulated
      Acanthamoeba of the pathogenic variety had relatively high background levels of
      test HSPs and seemed undisturbed by the types of stresses they must deal with
      when entering their hosts. These studies suggest that high HSP levels in
      amphizoic acanthamoebae may indicate their involvement in (i) tolerance induction
      to hosts' stressors and/or (ii) in species' virulence.

PMID- 10899528
TI  - Immunolocalization of macrophage adhesion molecule-1 and macrophage inflammatory
      protein-1 in schistosomal soluble egg antigen-induced granulomatous
      hyporesponsiveness.
AB  - This work studied the histopathological changes and the changes in the expression
      of macrophage adhesion molecule-1 (Mac-1) and macrophage inflammatory protein
      1alpha (MIP-1alpha) in a murine model of soluble egg antigen (SEA) - induced
      granulomatous hyporesponsiveness. Histopathological results of hepatic sections
      in an SEA group showed early acceleration of ova destruction and markedly
      diminished granuloma cellularity with eosinophils and macrophages still being the
      predominant cells. Later, giant cells and pigmented macrophages that were
      scattered among granuloma cells and in intimate contact with the deposited eggs
      were more predominant in the SEA group than in the infected control group.
      Concurrently, the counts of Mac-1 positive cells were significantly increased in
      liver sections of the SEA group than the infected control group during the course
      of infection. MIP-1alpha showed early higher counts followed by lower counts in
      the later stages of infection on granuloma cells in the SEA group than the
      infected control group. During the course of infection, similar distribution of
      Mac-1 and MIP-1alpha was present in both groups. This study suggests that
      sensitization with SEA probably leads to enhancement of phagocytic activity of
      macrophages via increasing expression of Mac-1 and hence engulfment of ic3b
      coated schistosomal products such as ova. It leads to rapid destruction of ova
      and hence decreases the host inflammatory response to infection and amelioration
      of hepatic pathology which would be a promising approach in reduction of host
      morbidity and mortality.

PMID- 10899529
TI  - Experimental Trypanosoma cruzi biclonal infection in Triatoma infestans:
      detection of distinct clonal genotypes using kinetoplast DNA probes.
AB  - Monitored biclonal densities of parasites were offered to third-stage larvae of
      Triatoma infestans via an artificial feeding device and 30 days later, the gut
      contents of the insects were processed for microscopic examination and polymerase
      chain reaction (PCR) detection of Trypanosoma cruzi kinetoplast DNA [kDNA]). A
      total of 15 mixtures involving nine different stocks attributed to the 19/20, 32
      and 39 major clonal genotypes of Trypanosoma cruzi were used. The presence of
      each T. cruzi clonal genotype after completion of the cycle through the insects
      was investigated by hybridising the PCR amplification products with genotype
      specific minicircle kDNA probes. Sixty-five out of 90 examined insects (72.2%)
      were positive for parasites by microscopic examination and 85 (94.4%) were
      positive by PCR. The results show that almost half of the biclonal infections are
      not detectable after completion of the cycle, and that there are important
      differences in detection of such biclonal infections according to the clonal
      genotypes considered. Moreover, elimination of a clonal genotype by another is a
      frequent, but not constant, pattern in biclonal infections of T. infestans. The
      use of PCR and kDNA probes makes it possible to avoid the culture phase, which
      makes detection of mixed infections much easier in epidemiological surveys.
      Moreover, the fact that T. infestansdoes not transmit different T. cruzi clonal
      genotypes with the same efficiency has strong implications for the reliability of
      xenogiagnosis.

PMID- 10899530
TI  - Temperature effects on embryonic development and the life cycle of
      Diphyllobothrium dendriticum.
AB  - Diphyllobothrium dendriticum eggs collected from hamster faeces were incubated at
      10 or 20 degrees C, or maintained at 4 degrees C for 11-30 months. On day 65, 20
      50% of eggs failed to hatch at 10 degrees C and 42-51% did not hatch by day 21 at
      20 degrees C. Our study indicates that eggs begin to hatch in mid-August and
      persist until October in many lakes within the natural range of D. dendriticum.
      Our results demonstrate that eggs stored at 4 degrees C will hatch, suggesting
      they can persist in the environment for long periods and contribute to the D.
      dendriticum life cycle in high Arctic lakes by hatching months or years after
      release.

PMID- 10899531
TI  - Characterisation of Toxoplasma gondii isolates using polymerase chain reaction
      (PCR) and restriction fragment length polymorphism (RFLP) of the non-coding
      Toxoplasma gondii (TGR)-gene sequences.
AB  - The Toxoplasma gondii (TGR) genes constitute a family of non-coding sequences,
      three of which have been previously described as possible tools for typing of
      Toxoplasma gondii isolates. We obtained new isolates of T. gondii from domestic
      and wild animals, and used these to evaluate the possibility of using TGR gene
      variants as markers to distinguish among T. gondii isolates from different
      animals and different geographical sources. Based on the band patterns obtained
      by restriction fragment length polymorphism (RFLP) analysis of the polymerase
      chain reaction (PCR) amplified TGR sequences, the T. gondii isolates could be
      separated into seven groups. Sequencing the amplified products showed that at
      least 20 TGR sequences not hitherto described had been found, demonstrating that
      the TGR gene family comprises a large number of different yet highly homologous
      sequences. Each isolate had its own unique TGR sequence. The TGR gene family
      therefore seems a promising target for typing individual T. gondii isolates and
      for studying the genetic distance between two isolates, which can be used for
      tracing routes of infection.

PMID- 10899532
TI  - Mapping of the N terminus of the Schistosoma mansoni tegumental antigen Sm15 to
      its predicted precursor protein.
AB  - Sm15 is a major Schistosoma mansoni 15 kDa tegumental antigen, resulting from the
      proteolytic processing of a larger precursor. The amino terminus of Sm15 was
      identified by direct amino acid sequencing, and the antigen was tentatively
      mapped to the segment spanning amino acids 362-497 of the precursor. This will
      allow subsequent studies to elucidate the possible immunological role of
      proteolytic processing in schistosomiasis.

PMID- 10899533
TI  - Identification by polymerase chain reaction (PCR) of Marshallagia marshalli and
      Ostertagia gruehneri from Svalbard reindeer.
AB  - A polymerase chain reaction (PCR) assay to identify two common abomasal nematodes
      Marshallagia marshalli and Ostertagia gruehneri of Svalbard reindeer was
      developed. Species-specific PCR primers were designed from internal transcribed
      spacer (ITS)-2 sequences of rDNA and validated using morphologically identified
      adult male and female nematodes. Using the species-specific primers, a 110 bp
      fragment was amplified from M. marshalli and its minor morph Marshallagia
      occidentalis and a 149 bp fragment was amplified from Ostertagia gruehneri and
      its minor morph Ostertagia arctica. No PCR products were amplified from the third
      rare species, Teladorsagia circumcincta, or DNA from the reindeer host. The assay
      provides a useful tool to estimate species composition for both sexes in this
      nematode community.

PMID- 10899534
TI  - Pigs become infected after ingestion of livers and lungs from chickens infected
      with Ascaris of pig origin.
AB  - An experimental infection with Ascaris of pig origin showed that Ascaris suum
      larvae can migrate extra-intestinally in chickens. Furthermore, after feeding
      piglets with Ascaris infected chicken liver and lungs, it was possible to recover
      larvae from their lungs. These observations suggest that the chicken could serve
      as a paratenic host for Ascaris. There is also the possibility for zoonotic
      transmission if raw chicken livers are consumed by humans.

PMID- 10899535
TI  - The impact of endogenous estradiol metabolites on carcinogenesis.
AB  - The available literature on estrogen metabolism and estrogen metabolites involved
      in carcinogenesis is reviewed. Endogenous estradiol metabolism leads to metabolic
      products that can have various, and, to some extent, contrary, biologic effects.
      Thus, there are numerous research findings on the stimulation and inhibition of
      cancer growth by estrogen metabolites. Furthermore, there are indications that,
      in certain types of cancer, the production of growth-stimulating estradiol
      metabolites is increased. There are also reports on substances that can influence
      estradiol metabolism. So far, only a few estradiol metabolites have been examined
      with respect to their influence on the development and growth of cancer. It is
      presumed that other metabolites can also intervene directly or indirectly in the
      cancer process, but there is a great lack of research in this area. An
      understanding of the actions of estradiol metabolites may open up new avenues for
      the therapy of malignant diseases. Although little is known about the biologic
      effects of most of the estradiol metabolites, the reported actions of certain
      estradiol metabolites already justify clinical investigations on their possible
      beneficial uses in tumor therapy.

PMID- 10899536
TI  - Regulation of collagenolytic cysteine protease synthesis by estrogen in
      osteoclasts.
AB  - In ovariectomized (Ovx) mice, collagenolytic cysteine protease (CCP) activity in
      calvaria significantly increased 7 days after ovariectomy and was about 50% of
      that observed in sham-operated (Sham) mice 3 weeks later. In Ovx mice,
      subcutaneously (s.c.) administered estradiol-17beta (E2) (10 microg/kg) for 2
      weeks led to a decrease in CCP activity in calvaria to the level observed in Sham
      mice. In Ovx mice, though the amount of cathepsin L increased more than that of
      cathepsin K, cathepsin K and cathepsin L content increased by 200-400% compared
      with the Sham mice; cathepsin K was detected in larger amounts than cathepsin L
      in calvaria from both Sham and Ovx mice. The amounts of cathepsin K and cathepsin
      L in Ovx mice were reduced to the values seen with Sham mice after administration
      (s.c.) of E2 (10 microg/kg) for 2 weeks. In mouse calvarial organ culture, the
      increase of CCP activity and release of hydroxyproline, an indicator of
      degradation of type-I collagen, in the presence of 1alpha,25-(OH)(2)D(3),
      parathyroid hormone, interleukin (IL)-1alpha, IL-6, or tumor necrosis factor
      alpha was suppressed by E2 (10(-9)-10(-7) M). In all cases, secretion of both
      cathepsin K and cathepsin L were suppressed by E2. In osteoclasts, expression of
      cathepsin K and cathepsin L was suppressed by E2 at the mRNA level. Cathepsin B
      was detected faintly or not at all. These results suggest that synthesis of
      cathepsin K and cathepsin L was negatively regulated by E2 at the mRNA level. In
      Ovx mice, deficiency of E2 resulted in an augmentation of cathepsin K and
      cathepsin L synthesis, and the cathepsins might share roles in bone resorption in
      vivo.

PMID- 10899537
TI  - Regioselective derivatization of ouabain with trialkylsilyl reagents and
      selective oxidation of the unprotected alcohols.
AB  - Many mammalian tissues contain cardiac glycoside-like steroids that inhibit the
      sodium pump. A ouabain-like compound has been described in the human circulation
      and suggested to be ouabain or a closely related isomer. Ouabain is a highly
      hydroxylated compound and one of the most potent inhibitors of the sodium pump.
      Trialkylsilyl derivatization of ouabain has been carried out to determine reagent
      selectivity among the eight hydroxy groups as a prelude to the synthesis of
      regiospecific isomers. Mono-, di-, tri-, and hexa-trialkylsilyl derivatives have
      been prepared with substitution at the 19-, the 3',19-, the 1,3',19-, and the
      1,2',3',4',11, 19-positions, respectively. Mass spectrometry and NMR confirmed
      the substitutions. Selective protection of the hydroxy groups allows selective
      oxidation of the unprotected steroid ring alcohols without oxidation of the 2'-
      and 4'-rhamnoside alcohols. Pyridinium dichromate oxidation of the di
      trialkylsilyl and tri-trialkylsilyl derivatives gave the 1,11-diketone and the 11
      ketone analogues, respectively. These regioselective reactions open a route to
      the synthesis of a series of closely related isomers of ouabain and other
      derivatives that may have useful structure-activity relationships and utility in
      the elucidation of the biosynthesis of ouabain-like compounds.

PMID- 10899538
TI  - O-(Acridinium)hydroxylamine (AHA): a reagent for the preparation of
      chemiluminescent acridinium oxime (AO)-steroid conjugates.
AB  - O-(Acridinium)hydroxylamine (AHA) reacted with a representative sample of oxo
      steroids (6-oxoestradiol, estrone, norethindrone, cortisol, progesterone, digoxin
      dialdehyde, and digitoxin dialdehyde) to produce chemiluminescent acridinium
      oxime (AO) conjugates in a single step in 37-68% yield after preparative HPLC.

PMID- 10899539
TI  - A practical large-scale synthesis of 17alpha-acetoxy-11beta-(4-N, N
      dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914).
AB  - A new practical synthesis of 17alpha-acetoxy-11beta-(4-N, N-dimethylaminophenyl)
      19-norpregna-4,9-diene-3,20-dione (CDB-2914) is described. The synthesis gives
      easily isolable solids at all steps and is amenable to large-scale process.

PMID- 10899540
TI  - Oxysterols: 27-hydroxycholesterol and its radiolabeled analog.
AB  - We describe a convenient and stereoselective route to the synthesis of 27
      hydroxycholesterol. Also its radiolabeled analog, 22, 23 di [(3)H]-27
      hydroxycholesterol with high specific radioactivity (55 Ci/mmol) was synthesized
      by this method. Julia condensation of steroidal 22-sulfone with aldehyde, led to
      the addition of the 23-27 carbon side chain building block to the steroid
      backbone. Formed in this reaction beta-hydroxysulfone moiety was reduced by
      sodium amalgam generate 22-23 unsaturated bond. Further reduction either by
      hydrogen or tritium furnished substrates for the synthesis of title compounds.

PMID- 10899542
TI  - High-field NMR studies of 3beta-tetrahydropyranyloxy steroids.
AB  - Comprehensive NMR studies were carried out on 3beta-hydroxy-pregnene and
      cholestene analogs, each containing a tetrahydropyranyl ether group at the 3
      position. Two-dimensional NMR experiments (COSY, TOCSY, HSQC, and HSQC-TOCSY)
      permitted the complete assignments of both the (1)H and (13)C resonances of these
      derivatives in deuterated benzene or chloroform. The aromatic solvent-induced NMR
      signal shifts (ASIS) were also investigated.

PMID- 10899541
TI  - Estrogen and progesterone modulation of eosinophilic infiltration of the rat
      uterine cervix.
AB  - Ripening of the rat cervix involves widespread collagenolysis that follows an
      eosinophilic leukocyte infiltration. The hormonal control of these events is not
      well understood. The aims of this study were to investigate the mechanism through
      which progesterone (P) and 17beta-estradiol (E(2)) modulate eosinophilic invasion
      and to determine if this event is protein synthesis mediated. Cervical
      eosinophilic invasion was measured in intact rats during the second half of
      pregnancy and compared with values from ovariectomized (O) pseudopregnant (PSP)
      rats treated with P and E(2) in doses that mimicked the levels of pregnancy.
      Other O-PSP rats were treated with an E(2) antagonist (tamoxifen) and the
      antiprogestin RU-486. To study the role of protein synthesis in eosinophilic
      invasion of the cervix, rats were treated with actinomycin-D (an inhibitor of
      mRNA synthesis), and animals were sacrificed on D21 or D22 to evaluate
      eosinophilic invasion. Rats treated with E(2) showed high levels of infiltration
      and tamoxifen blocked this E(2) effect. On the other hand, P antagonized the
      stimulatory effects of E(2) on eosinophilic invasion, however when the P and E(2)
      treated rats were injected with RU-486 the inhibitory effect of P was reversed.
      In intact pregnant rats a sharp rise in eosinophilic infiltration was detected on
      D23, 20 h after the fall of serum P. Finally, E(2) treated rats injected with
      actinomycin-D had no invasion of eosinophils. In conclusion, the estrogen
      triggered eosinophil invasion is affected by the classic estrogen receptor
      antagonist tamoxifen and by the mRNA synthesis blocker actinomycin-D suggesting a
      genomic action of E(2). Furthermore, the estrogen effect is blocked by P and this
      inhibition is reversed by RU-486.

PMID- 10899543
TI  - Kinetics and mechanisms of reactions catalyzed by immobilized lipases*
AB  - This review focuses on the kinetics of several modes of immobilization of
      lipases, on the mechanisms of reactions of activation of immobilized lipases, and
      on the kinetics and mechanisms of reactions catalyzed by immobilized lipases. A
      comprehensive overview of the state of the art pertaining to structural features
      of lipases is provided as an aid to understand immobilization, interfacial
      activation, and catalytic performance. General rate expressions are duly derived;
      more frequent simplifying assumptions are stated and the results thereof listed.
      Physicochemical and statistical significance of parameters in rate expressions
      fitted to experimental data are also discussed whenever possible.

PMID- 10899544
TI  - Candida cloacae oxidation of long-chain fatty acids to dioic acids.
AB  - Candida cloacae cells oxidize long-chain fatty acids to their corresponding
      dicarboxylic acids (dioic acids) at rates dependent on their chain length and
      degree of saturation. This is despite the well-known toxicity of the fatty acids.
      Among the saturated substrates, the oxidation is limited to lauric acid (C12).
      The addition of pristane (5% v/v), which acts as an inert carrier for the poorly
      water-soluble substrate, boosts the oxidation of lauric acid to a rate that is
      comparable to that of dodecane. When dissolved in pristane, myristic (C14) and
      palmitic (C16) acids are effective carbon sources for C. cloacae, but dioic acid
      production is very low. Media glucose concentration and pH also influence cell
      growth and productivity. After the glucose is depleted, oxidation is optimal at a
      low pH. A two-phase (pristane/water) reaction was tested in a 2-l stirred tank
      bioreactor in which growth and oxidation were separated. A 50% w/w conversion of
      lauric acid (10 g/l) to dodecanedioic acid was achieved. The bioreactor also
      alleviated poor mass transfer characteristics experienced in shake flasks.

PMID- 10899545
TI  - Characteristics of levan fructotransferase from Arthrobacter ureafaciens K2032
      and difructose anhydride IV formation from levan.
AB  - A microorganism producing levan fructotransferase was isolated from sugar
      disclosed soil and it was identified as Arthrobacter ureafaciens. The major
      product from levan by enzyme reaction was identified as di-D-fructofuranose
      2,6':6,2' dianhydride by mass spectrometry, nuclear magnetic resonance, and
      chemical analyses. Small amounts of several oligosaccharides and free fructose
      were also formed by enzyme reaction. An extracellular enzyme that produces di-D
      fructofuranose 2,6':6,2' dianhydride from levan was purified from the culture
      broth of A. ureafaciens K2032. The enzyme had optimum activity around pH 5.8 and
      45 degrees C and had a dimeric form in solution. The N-terminal amino acid
      residues of the purified enzyme were SAPGSLRAVYHMTPPSGXLXDPQ. The enzyme has
      narrow substrate range and converts the levan to di-D-fructofuranose 2,6':6,2'
      dianhydride with around 62.5% conversion yield.

PMID- 10899546
TI  - Production and characterization of glutathione-S-transferase fused with a poly
      histidine tag.
AB  - Schistosoma japonicum glutathione-S-transferase (SjGST) was genetically
      engineered with a poly-histidine tag at the C-terminus and highly expressed in
      Escherichia coli. Both SjGST and the tagged protein, SjGST/His, were purified
      with glutathione Sepharose 4B gels and subsequently studied for their activities,
      antibody-binding abilities, and metal affinities. The production level of active
      SjGST/His was higher than that of SjGST. Both proteins had similar specific
      catalytic activities and binding abilities with anti-SjGST antibody, while the
      antibody against poly-histidine recognized only SjGST/His. Proteolytic
      degradation was occasionally observed in aged dialyzed SjGST/His preparation.
      Under a native condition, the Co(2+)-chelated TANOL gel (Co-TANOL) had a better
      binding specificity to the tagged protein than did the Ni(2+)-chelated
      nitriloacetic acid (Ni-NTA) agarose gel. However, the binding capacity of the Ni
      NTA gel for SjGST/His was 2-fold higher than that of the Co-TANOL one. To
      increase the native binding specificity of the Ni-NTA gel, 20 mM imidazole had to
      be added to the washing solution. In a denatured state, both gels could only
      capture SjGST/His, and the binding capacity of the Ni-NTA gel was nearly 2-fold
      higher than that of the Co-TANOL gel. The binding association constants of both
      gels with SjGST/His did not differ greatly under either condition. The study
      demonstrated that the C-terminal addition of the poly-histidine tag to SjGST
      increased the metal affinity of the enzyme to the Co-TANOL gel under both native
      and denaturing conditions and to the Ni-NTA gel under denaturing conditions,
      whereas the enzymatic activity and antibody-binding ability were not affected.

PMID- 10899547
TI  - Expression of Bacillus circulans Teri-42 xylanase gene in Bacillus subtilis.
AB  - The xylanase gene of Bacillus circulans Teri-42 was cloned in both B. subtilis
      and Escherichia coli. The enzyme activity was almost 87% higher in B. subtilis
      (pBA7) than in E. coli (pAQ4). No cellulase activity was detected in the clones,
      B. subtilis (pBA7) and E. coli (pAQ4). Approximately 1120 U (80%) of the xylanase
      was secreted extracellularly by the clone B. subtilis (pBA7) as compared to 79 U
      (88%) excreted in E. coli (pAQ4). In B. subtilis (pBA7) the optimal xylanase
      activity was at pH 7.0 and 50 degrees C, which was the same as that of the parent
      B. circulans Teri-42. The recombinant xylanase in B. subtilis was more stable at
      higher temperatures than the parent B. circulans Teri-42. Purification of
      xylanase from the clone B. subtilis (pBA7) showed a 71 kDa polypeptide similar to
      that observed in B. circulans Teri-42.

PMID- 10899548
TI  - Effect of hydrogen peroxide on d-amino acid oxidase from Rhodotorula gracilis.
AB  - D-amino acid oxidase from Rhodotorula gracilis is a FAD-containing enzyme that
      belongs to the oxidase class that is characterized by the ability of the reduced
      flavin to react quickly with oxygen, yielding hydrogen peroxide and the oxidized
      cofactor. Hydrogen peroxide, necessary for the production of glutaryl-7-ACA from
      cephalosporin C had a deleterious effect on the enzyme. H(2)O(2) induced the
      oxidation of tryptophan and cysteine residues of the protein that could be
      involved in the dimerization process, required for the attainment of a fully
      competent enzyme. H(2)O(2) had also a kinetic effect on the reaction catalyzed by
      D-amino acid oxidase. It was a pure noncompetitive inhibitor; the corresponding
      inhibition constants were K(is) = 0.52 mM and K(ii) = 0.70 mM.

PMID- 10899549
TI  - The effect of overliming on the toxicity of dilute acid pretreated
      lignocellulosics: the role of inorganics, uronic acids and ether-soluble
      organics.
AB  - Although the treatment of dilute acid pretreated lignocellulosics with calcium
      hydroxide or carbonate (overliming) is known to improve the fermentability of
      carbohydrate-rich hydrolyzate streams, a firm understanding of the chemistry
      behind the process is lacking. Quantitative evaluation of inorganics, uronic
      acids, and non-polar organics indicates that only a portion of the improvement
      can be ascribed to these materials. Upon overliming the concentrations of
      inorganics either increase (Ca, Mg), decrease (Fe, P, Zn, K) or remain relatively
      the same (Al, Na). Furthermore, organic compounds that are not extractable with
      tert-butyl methyl ether (MTBE) are toxic to Zymomonas mobilis CP4(pZB5).
      Overliming and direct neutralization are somewhat effective in removing sulfate
      anions, although sulfate toxicity is considerably less than that of acetic acid.
      Uronic acids were found to be non-toxic under pH controlled conditions.

PMID- 10899550
TI  - Effect of the growth conditions on the synthesis of a recombinant beta-1,4
      endoglucanase in continuous and fed-batch culture.
AB  - Continuous culture and fed-batch fermentations were used to test the behavior of
      the system Bacillus subtilis DN1885(pCH7) that synthesizes a recombinant beta-1,4
      endoglucanase. Continuous culture experiments were focused on the study of the
      instability aspects of the system as well as determination of the biomass growth
      rate range at which the recombinant enzyme synthesis was improved. Fed-batch
      fermentations were carried out to study the possibility of enhancing recombinant
      enzyme synthesis through the control of medium addition. It was found that, in
      continuous culture fermentations, the culture is less unstable at low dilution
      rates (dilution rate < 0.1 h(-)(1)). Also, low dilution rates give a higher
      specific recombinant enzyme concentration (10 times more than that obtained at
      high dilution rates). In fed-batch fermentation, the final recombinant enzyme
      concentration can be manipulated through the medium addition strategy. To
      increase the recombinant enzyme concentration, the carbon source has to be fed
      slowly, otherwise enzyme synthesis is impaired due to catabolite repression.
      Therefore, an increase in the biomass concentration does not necessarily imply an
      increase in the recombinant enzyme concentration. Higher recombinant enzyme
      concentrations were found in fed-batch fermentations compared to those obtained
      in continuous culture.

PMID- 10899551
TI  - Reversibly soluble biocatalyst: optimization of trypsin coupling to Eudragit S
      100 and biocatalyst activity in soluble and precipitated forms.
AB  - Eudragit S-100, a copolymer of methacrylic acid and methyl methacrylate is
      soluble at pH above 5 and insoluble at pH below 4.5. pH-dependent solubility of
      the polymer is used for the development of reversibly soluble biocatalyst, which
      combines the advantages of both soluble and immobilized biocatalysts. Activity of
      trypsin, covalently coupled to Eudragit S-100, was improved by protecting the
      active site of the enzyme with benzamidine and removing the noncovalently bound
      proteins with Triton X-100 in 0.15 M Tris buffer (pH 7.6). Accurate choice of
      coupling conditions combined with proper washing protocol produced highly active
      enzyme-polymer conjugate with no noncovalently bound protein. Two conjugates with
      100-fold difference in the content of trypsin coupled to Eudragit S-100 were
      studied when the preparations were in soluble and precipitated forms. The
      K(m)values of the soluble enzyme to the lower molecular weight substrate was less
      than that of the free enzyme, whereas that to the higher molecular weight
      substrate was closer to that of the free enzyme. Activities of the soluble and
      precipitated immobilized trypsin with higher molecular weight substrate were
      completely inhibited by soy bean trypsin inhibitor, whereas complete inhibition
      with soy bean trypsin inhibitor was never achieved with lower molecular weight
      substrate, indicating reduced access of high-molecular weight substrate/inhibitor
      to some of the catalytically active enzyme molecules in trypsin-Eudragit
      conjugate.

PMID- 10899552
TI  - The effect of stirring and seeding on the AcPheLeuNH(2) synthesis and
      crystallization in a reversed micellar system.
AB  - The present work describes the enzymatic synthesis and simultaneous
      crystallization of the dipeptide AcPheLeuNH(2) by alpha-chymotrypsin in a
      reversed micellar system of tetradecyltrimethylammonium bromide
      (TTAB)/heptane/octanol/carbonate buffer. The low solubility of the dipeptide in
      the micellar solution led to the formation and growth of needle-like crystals
      during the synthesis as soon as supersaturation was achieved. The crystallization
      process then followed a typical pattern, proceeding in three phases: nucleation,
      de-supersaturation, and re-equilibrium of saturation. Crystallization was
      followed by visual observation with an optical microscope, and the increase of
      crystal number and size was confirmed. Experiments showed that the
      supersaturation concentration decreases with the addition of AcPheLeuNH(2) seeds
      before the reaction, and also with a decrease of the stirring speed. It was also
      observed that the increase of both seed concentration and stirring advances the
      start of crystallization, so that the dipeptide is more quickly removed from
      solution. The consequent decrease in its loss through hydrolysis causes an
      increase in its yield. Both stirring and seeding could constitute important
      generic strategies for promoting crystallization of more soluble dipeptides
      during their synthesis in similar reversed micellar systems.

PMID- 10899553
TI  - Temperature optimization for reactor operation with chitin-immobilized lactase
      under modulated inactivation.
AB  - Temperature effects on all kinetic and inactivation parameters have been
      determined for chitin immobilized lactase from Kluyveromyces marxianus var.
      marxianus, and proper temperature functions have been validated. Maximum reaction
      rate, Michaelis constant referred to lactose, inhibition constant for galactose
      and inactivation rates increased with temperature. Enzyme inactivation was
      adequately modelled by a two-stage series mechanism. The effect of galactose and
      lactose on enzyme inactivation was determined in terms of modulation factors that
      were positive for galactose and negative for lactose over the whole range of
      temperature studied. Modulation factors were mild functions of temperature in the
      first stage and strong functions in the second stage of CIL inactivation where
      galactose positive modulation factors increase with temperature and lactose
      negative modulation factors decrease with temperature. Temperature explicit
      functions for all kinetic and inactivation parameters were incorporated into a
      scheme to optimize the temperature of operation for a sequential batch reactor
      with chitin-immobilized lactase, based on an annual cost objective function for
      reactor operation. Software for temperature optimization was developed creating a
      friendly interface with user that allows the introduction of variations in all
      parameters and operational criteria to perform sensitivity analysis.

PMID- 10899554
TI  - Acetylcholine biosensor involving entrapment of acetylcholinesterase and
      poly(ethylene glycol)-modified choline oxidase in a poly(vinyl alcohol) cryogel
      membrane.
AB  - A bienzymatic sensor for the determination of acetylcholine was prepared by
      physical coimmobilization of acetylcholinesterase and poly(ethylene glycol)
      modified choline oxidase in a poly(vinyl alcohol) cryogel membrane obtained by a
      cyclic freezing-thawing process. The enzyme-modified polymer was applied on a
      platinum electrode to form an amperometric sensor, based on the electrochemical
      detection of enzymatically developed hydrogen peroxide. The analytical
      characteristics of this sensor, including calibration curves for choline and
      acetylcholine, pH, and temperature effects, and stability are described.

PMID- 10899555
TI  - Hydrolysis and large scale ultrafiltration study of alfalfa protein concentrate
      enzymatic hydrolysate.
AB  - Batch enzymatic hydrolysis of insoluble Alfalfa Protein Concentrate by Delvolase
      was carried out at laboratory and at pilot-plant scale coupled to an
      ultrafiltration reactor with a mineral tubular membrane. Parametric studies were
      carried out on the batch system to determine the biochemical and hydrodynamical
      optimum conditions. The hydrolysis conditions selected were 40 degrees C, pH 9.5,
      initial substrate level 3 g protein/100 g and the enzyme substrate ratio 152 U/g
      protein. After 5 h of hydrolysis, 96% of the total amount of initial nitrogen was
      solubilized. The ultrafiltration conditions selected were a 10 000 Nominal
      Molecular Weight Cut-Off, a transmembrane pressure of 1.5 bar, a flux velocity of
      0.8 m/s. Fifty percent of the initial nitrogen appeared in the permeate.

PMID- 10899556
TI  - Effect of fatty acids on the mycelial growth and polysaccharide formation by
      Ganoderma lucidum in shake flask cultures.
AB  - Fatty acids were added into the media to investigate their effects on the
      mycelial growth and polysaccharide formation by Ganoderma lucidum. The
      experiments were carried out in freely suspended cultures or immobilized cultures
      using shake flasks. The results indicate that the extent of stimulation or
      inhibition were associated with the types and levels of fatty acids. Oleic acid
      at the level of 0.15 g/100 ml led to a significant increase in cell concentration
      from 0.20 to 0.46 g/100 ml in a suspended culture and palmitic acid was of great
      advantage to polysaccharide production. In contrast, linoleic acid (0.1 g/100 ml)
      drastically suppressed both mycelial growth and polysaccharide formation. In
      immobilized cultures with fatty acids, the stimulation of mycelial growth
      remained the same level, but the enhancement of polysaccharide production became
      less. In addition, the growth of G. lucidum in the pattern of immobilization
      might be beneficial to the production of mycelia and polysaccharide.

PMID- 10899557
TI  - Production of high-oleic acid tallow fractions using lipase-catalyzed directed
      interesterification, using both batch and continuous processing.
AB  - Immobilized lipases were used to catalyze batch-directed interesterification of
      tallow, resulting in oleins containing significantly higher levels of unsaturated
      fatty acids than obtained by fractionation without lipase. After 14 days, a
      reaction catalyzed by 2% Novozym 435 yielded 57% olein unsaturation, compared
      with 45% in a no-enzyme control. Free fatty acid levels increased to 2-3% during
      reactions. Incubation of the enzyme in multiple batches of melted fat caused a
      gradual loss of interesterification activity, apparently due to progressive
      dehydration. The activity could be restored by addition of water to the reaction
      medium. Immobilized lipase was also used to catalyze directed interesterification
      in a continuous flow reactor. Melted tallow was circulated through a packed bed
      enzyme reactor and a separate crystallization vessel. The temperatures of the two
      parts of the apparatus were controlled separately to allow crystallization to
      occur separately from interesterification. Operation of the reactor with
      conventionally dry, prefractionated tallow allowed the formation of an olein
      consisting of up to 60% unsaturated fatty acids. The greatest changes in olein
      fatty acid composition were achieved when the fractionation temperature was kept
      constant at a value that promoted selective crystallization of trisaturated
      triglycerides that were continuously produced by enzymic interesterification. The
      enzyme could be reused without apparent loss of activity, and its activity was
      apparently enhanced by preincubation in melted tallow for up to several days.
      Control of both the water activity of the enzyme and tallow feedstock and of the
      absorption of atmospheric water vapor were required to maintain enzyme activity,
      during multiple reuse and minimize free fatty acid formation. This method may
      form the basis for a process to produce highly mono-unsaturated tallow fractions
      for use in food applications (e.g. frying) where a "healthy" low saturated fat
      product is required.

PMID- 10899558
TI  - Heterotrophic production of biomass and lutein by Chlorella protothecoides on
      various nitrogen sources.
AB  - The effects of nitrate, ammonium, and urea as nitrogen sources on the
      heterotrophic growth of Chlorella protothecoides were investigated using flask
      cultures. No appreciable inhibitory effect on the algal growth was observed over
      a nitrogen concentration range of 0.85-1.7 g l(-)(1). In contrast, differences in
      specific growth rate and biomass production were found among the cultures with
      the various nitrogen compounds. The influence of different nitrogen sources at a
      concentration equivalent to 1.7 g l(-)(1) nitrogen on the heterotrophic
      production of biomass and lutein by C. protothecoides was investigated using the
      culture medium containing 40 g l(-)(1) glucose as the sole carbon and energy
      source in fermentors. The maximum biomass concentrations in the three cultures
      with nitrate, ammonium, and urea were 18.4, 18.9, and 19.6 g l(-)(1) dry cells,
      respectively. The maximum lutein yields in these cultures were between 68.42 and
      83.81 mg l(-)(1). The highest yields of both biomass and lutein were achieved in
      the culture with urea. It was therefore concluded that urea was the best nitrogen
      source for the production of biomass and lutein. Based on the experimental
      results, a group of kinetic models describing cell growth, lutein production, and
      glucose and nitrogen consumption were proposed and a satisfactory fit was found
      between the experimental results and predicted values. Dynamic analysis of models
      demonstrated that enhancing initial nitrogen concentration in fermentor cultures,
      which correspondingly enhances cell growth and lutein formation, may shorten the
      fermentation cycle by 25-46%.

PMID- 10899559
TI  - Glucose oxidase release from calcium alginate gel capsules.
AB  - Diffusion of glucose oxidase within calcium alginate gel capsules has been
      assayed and the experimental data fitted to a simple semi-empirical power
      equation, which is used to analyse the solute release from polymeric devices. It
      was found that an increase in the concentration of sodium alginate and calcium
      chloride gives rise to a reduction in the enzyme leakage. This was verified when
      glucose oxidase (GOD) diffusion percentages were compared in capsules with
      thicknesses of the same order of magnitude but obtained under different
      experimental conditions. So, the use of sodium alginate and calcium chloride
      solutions of concentrations 0.5% w/v and 2.6% w/v, respectively, lead to a
      diffusion percentage of 25 +/- 2. This percentage was reduced to 8 +/- 3 when
      sodium alginate and calcium chloride concentrations were fixed at 1% w/v and 4%
      w/v, respectively, even though the thicknesses of the capsules were of the same
      order of magnitude.

PMID- 10899560
TI  - Effects of agitation level on the adsorption, desorption, and activities on
      cotton fabrics of full length and core domains of EGV (Humicola insolens) and
      CenA (Cellulomonas fimi).
AB  - The activities (at pH 7 and 50 degrees C) of purified EGV (Humicola insolens) and
      CenA (Cellulomonas fimi) were determined on cotton fabrics at high and low levels
      of mechanical agitation. Similar activity measurements were also made by using
      the core domains of these cellulases. Activity experiments suggested that the
      presence of cellulose binding domains (CBDs) is not essential for cellulase
      performance in the textile processes, where high levels of mechanical agitation
      are applied. The binding reversibilities of these cellulases and their cores were
      studied by dilution of the treatment liquor after equilibrium adsorption. EGV
      showed low percentage of adsorption under both levels of agitation. It was
      observed that the adsorption/desorption processes of cellulases are enhanced by
      higher mechanical agitation levels and that the binding of cellulase with CBD of
      family I (EGV) is more reversible than that of CBD of the cellulase of family II
      (CenA).

PMID- 10899561
TI  - Characterization and immobilization of the laccase from Pleurotus ostreatus and
      its use for the continuous elimination of phenolic pollutants.
AB  - A laccase, the only ligninolytic enzyme produced by the basidiomycete Pleurotus
      ostreatus strain RK 36 was purified to homogeneity and characterized. The enzyme
      is a monomeric protein with a molecular weight of 67 000 Da and an isoelectric
      point of 3.6. Type I and type III Cu(2+) centers were identified by
      spectrophotometry. With syringaldazine as substrate laccase showed the highest
      oxidation rates at pH 5.8, 50 degrees C, and in 40 mM phosphate buffer. Among the
      tested stabilization parameters laccase retained most of its activity in high
      ionic buffer, pH 10, -20 degrees C, in the presence of 10 mM benzoic acid and
      with 35% ethylene glycol respectively. Crude laccase was covalently immobilized
      to Eupergit((R))C. Benzoate was found to stabilize the enzyme during the
      immobilization process. The activity loss of laccase during 10 days at 25 degrees
      C storage was 2% on average. Continuous elimination of 2,6-dimethoxyphenol by
      immobilized laccase was carried out in a packed bed reactor followed by
      filtration of the formed precipitate. The solubility of the polymerisates of
      oxidized syringaldazine, o-dianisidine, and 2,6-dimethoxyphenol with respect to
      temperature, pH-value and organic solvents were examined. The precipitates were
      found to be insoluble under non-extreme environmental conditions.

PMID- 10899562
TI  - A mathematical model of the formation of fermentable sugars from starch
      hydrolysis during high-temperature mashing.
AB  - During the mashing process of brewing, activity of the amylolytic enzymes decays
      due to the high temperatures used to gelatinise the starch. Because the different
      enzymes produce different sugars, high temperatures can be exploited to modify
      the fermentability of resulting worts. This is especially useful when producing
      low alcohol beers. The expression a.exp(b.t)-c.exp(d.t) (where t is the
      temperature of the mash in degrees C) provides a simple but useful description of
      the activity of the amylases. Combining the activities of alpha- and beta
      amylases results in a prediction of the resulting fermentability. A simple
      modification to the expression accommodates changes in mash thickness. The error
      of prediction is approximately 3 degrees of fermentability. The model is not
      appropriate for predicting the fermentability of worts produced at the lower
      standard mashing temperatures. It can be used without the necessity of analytical
      parameters so analyses that the brewer would not normally perform are not
      required. If increased accuracy is needed, the results of two previous mashes can
      be used to modify the parameters used.

PMID- 10899565
TI  - The expression and structure of TGF-beta2 transcripts in rat muscles.
AB  - The transforming growth factor-beta2 (TGF-beta2) transcripts expressed in various
      tissues of rat were characterised by RT-PCR and the nucleotide sequence of the
      cDNAs determined. A transcript with an 84-nucleotide insert in the latency
      associated peptide region, the long form, was found. The long form of TGF-beta2
      was detected in the aorta, primary bronchus, uterus, heart, skeletal muscle,
      sciatic nerve and spinal cord but not in the intestine. The 3' untranslated
      region of TGF-beta2 contained several putative AU-rich elements and multiple
      polyadenylation sites, indicating post-transcriptional regulation of TGF-beta2
      synthesis. The levels of TGF-beta2 transcripts were estimated using semi
      quantitative RT-PCR. They were down-regulated during muscle development and up
      regulated after denervation. The long form constituted approximately 6% of the
      total TGF-beta2 messages in skeletal muscle.

PMID- 10899572
TI  - Mouse integrin alphav promoter is regulated by transcriptional factors Ets and
      Sp1 in melanoma cells.
AB  - A 17-bp region between the -31 and -15 bp region of the mouse integrin alphav
      gene is known to be one of the cis-acting elements for promoter activity.
      Experimental binding of nuclear proteins to the -31/-15 region reveals that the 
      27/-16 region mediates the binding. The -27/-16 region, GGCTCCTCCTCC, has a
      TCCTCC motif, one of the Sp1 binding motifs. An anti-Sp1 IgG and an Sp1-binding
      oligonucleotide interfered with the binding of nuclear proteins to the -27/-16
      oligonucleotide, demonstrating that Sp1 binds to the -27/-16 region. In addition
      to the -27/-16 region, two other regions, -108/-89 and -64/-44, were found to
      bind to nuclear proteins within the -108/+1 alphav promoter region. An
      oligonucleotide containing the Ets-binding consensus sequence of CAGGAAGT
      interfered with their binding, indicating that both regions have a functional Ets
      binding site; which is ACGGAAGT from -106 to -99 bp and ACTTCCTC from -61 to -54
      bp, as deduced from the sequence. Mutations in or deletions from any one of three
      cis-acting elements, the two Ets-binding sites or one Sp1-binding site,
      remarkably decreased the promoter activity detected in the -108/+1 region.
      Cotransfection of both Sp1 and Ets-1 cDNAs with the -108/+1 region into B16F10
      cells increased the promoter activity 2.9-fold. These results demonstrate that
      Sp1 and Ets cooperate to activate the -108/+1-alphav promoter region.

PMID- 10899575
TI  - Structure and heterologous expression of a gene encoding fructose-6-phosphate,2
      kinase/fructose-2,6-bisphosphatase from Arabidopsis thaliana.
AB  - A full-length cDNA clone encoding fructose-6-phosphate, 2-kinase/fructose-2,6
      bisphosphatase from Arabidopsis thaliana (AtF2KP) was isolated. The encoded
      protein is composed of two different regions: (i) a 400 amino acid COOH-terminal
      region, covering the catalytic region of the protein which is homologous to
      enzymes from other eukaryotes. This region is highly conserved among plant
      species (88% identity to spinach F2KP). (ii) A 345 amino acid plant-specific
      NH(2)-terminal region, with 59% identity to spinach F2KP, which is composed of
      homologous motifs and intermittent variable sequences. Western blots show that
      F2KP from several plant species migrates in sodium dodecyl sulphate
      polyacrylamide gel electrophoresis as a similar sized (93 kDa) protein. AtF2KP
      was expressed in Escherichia coli as a full length and a truncated (without the
      NH(2)-terminal region) fusion protein. Both forms had kinase as well as
      phosphatase activity, but presence of the NH(2)-terminal region influenced the
      ratio between the two activities. It is suggested that the NH(2)-terminal region
      represents a regulatory region, which defines specific properties of the plant
      enzymes. A genomic clone for the corresponding gene, AtF2KP, was isolated. The
      clone (9519 bp) included 23 exons, 22 introns and the promoter sequence. Southern
      blot analysis showed only one copy of the gene in the A. thaliana genome.

PMID- 10899580
TI  - Cloning and characterization of the proximal promoter region of the mouse
      glutamate-L-cysteine ligase regulatory subunit gene.
AB  - We describe upregulation of the mRNA for the mouse glutamate-cysteine ligase
      regulatory subunit gene (Glcl-r) in Hepa-1 cells treated with beta-napthoflavone
      (BNF) and tert-butylhydroquinone (tBHQ). A 2-kb fragment of the proximal promoter
      region of the gene was cloned and sequenced, and sequence analysis reveals a high
      degree of homology when compared to the human glutamate-cysteine ligase
      regulatory subunit gene promoter. Primer extension analysis indicates a major
      transcription start site 218 bp upstream of the translation start codon in a CpG
      rich region, suggesting that transcription is Sp1 mediated. Reporter constructs
      containing nested deletion fragments of the Glcl-r promoter demonstrate that
      regulatory elements sufficient for basal and tBHQ-inducible expression lie
      between -273 and -787 bp relative to the translation start codon and that the
      distal promoter may contain negative regulatory elements.

PMID- 10899581
TI  - Identification and characterization of conserved cis-regulatory elements in the
      human keratocan gene promoter.
AB  - Keratocan, along with lumican and mimecan, represent the keratan sulfate
      containing proteoglycans of the vertebrate cornea that play a key role in
      development and maintenance of corneal transparency. In this study, we cloned 4.1
      kb of the human Kera 5'-flanking region and characterized the promoter structure.
      Using primer extension and ribonuclease protection assay, we identify two major
      transcriptional start sites in the first exon. Using luciferase reporter gene
      transfection analysis of 5'-deletion and mutation constructs, we demonstrate
      positive and negative regulatory elements within a 1.3 kb upstream sequence.
      Comparison of human and bovine 5'-flanking sequences reveals three highly
      conserved regions: a 450 bp region in the first exon, a 92 bp promoter proximal
      conserved regulatory region identified as an enhancer in the natural context, and
      a 223 bp promoter distal conserved regulatory region identified as a silencer
      both in the natural context and in a heterologous promoter system. In addition, a
      conserved CArG-box residing 851 bp upstream of the first transcription start site
      also can lead to the repression of Kera expression in cultured corneal
      keratocytes. DNaseI footprinting and electrophoretic mobility shift assay
      demonstrate that cell type-specific factors bind to regulatory elements located
      in the conserved regions. Competition experiments indicate that the CTC factor
      and a protein that binds to the CAGA motif are likely to be among the multiple
      factors involved in the transcriptional regulation of the human Kera gene.

PMID- 10899582
TI  - Molecular cloning and characterization of the human phosducin-like protein
      (hPhLP) promoter.
AB  - Phosducin-like protein (PhLP) is an inducible Gbetagamma binding protein which is
      hypothesized to be a ubiquitous G protein regulator. To elucidate the mechanisms
      regulating the expression of the human PhLP (hPhLP) gene, we have cloned and
      characterized its 5'-flanking region. Primer extension analysis identified a
      major transcription initiation site 172 bp upstream of the ATG start codon.
      Analysis of the 5'-flanking region revealed that, although it lacked a TATA box
      element, the hPhLP promoter did contain several consensus binding motifs
      including AP4, CCAAT, CREB, NF-kappaB, SP1 and E2F. Transient transfection
      analyses using a series of 5'-flanking deletion/luciferase reporter gene
      constructs identified a 25 bp sequence (-80 to -55 bp) that is necessary for
      basal level transcription of the hPhLP gene in all the cell lines investigated.
      Interestingly, dependent upon the cell line, distinct transcription factors bind
      to this region suggesting that basal level hPhLP gene transcription may be
      regulated in a tissue-specific manner.

PMID- 10899584
TI  - Drosophila protein phosphatase 5 is encoded by a single gene that is most highly
      expressed during embryonic development.
AB  - A putative Drosophila melanogaster homologue of mammalian PP5, termed Dm PP5, was
      identified from cDNA. Dm PP5 comprises a phosphatase catalytic domain preceded by
      an amino terminal domain containing three tetratricopeptide repeat motifs and
      shares 60% overall amino acid identity with human PP5. Genomic restriction
      analysis identified a single Dm PP5 gene that was mapped to the third chromosome
      at locus 85E10-12 and a strain carrying a deletion that encompasses this gene was
      identified. Dm PP5 mRNA and protein are more highly expressed in the embryo than
      at later developmental stages, but their expression levels do not always change
      synchronously. Dm PP5 protein localises to both the nucleus and the cytoplasm of
      cells at the periphery of newly cellularized embryos.

PMID- 10899586
TI  - Cloning and recombinant expression of the La RNA-binding protein from Trypanosoma
      brucei.
AB  - We report the isolation, cloning and recombinant expression of a Trypanosoma
      brucei homolog of the La RNA-binding protein. Based on peptide sequence
      information we have isolated a cDNA clone which encodes a protein of 335 amino
      acids with a predicted molecular weight of 37.7 kDa. The amino acid sequence fits
      the domain structure of known La proteins and contains a putative ATP-binding
      site located in the COOH-terminal domain. The cDNA was expressed as a glutathione
      S-transferase fusion protein in Escherichia coli, and the recombinant protein
      displayed RNA-binding activity in an electrophoretic mobility shift assay.

PMID- 10899588
TI  - Cloning and expression of genes encoding meta-cleavage enzymes from 4,6
      dimethyldibenzothiophene-degrading Sphingomonas strain TZS-7.
AB  - Sphingomonas strain TZS-7 was reported as the first strain to have the ability to
      degrade 4,6-dimethyldibenzothiophene (4,6-dmDBT) by the ring-destructive pathway.
      Two genes for meta-cleavage dioxygenases were cloned from strain TZS-7.
      Expression of each gene showed that one enzyme was specific for 2,3
      dihydroxybiphenyl while another was more specific for catechol. The genes for the
      two enzymes were named dmdC and catA. The analysis of deduced amino acid
      sequences indicates that CatA falls into the class of meta-cleavage dioxygenases
      acting on dihydroxylated monocyclic compounds and DmdC falls into the class of
      meta-cleavage dioxygenases acting on dihydroxylated polycyclic compounds.

PMID- 10899593
TI  - Evolutionary conservation of gene structures of the Pax1/9 gene family.
AB  - Based on amino acid sequence comparisons, Pax1 and Pax9 genes are considered to
      form a subgroup of vertebrate Pax genes. We show here that the gene structures of
      mouse Pax1, human PAX9 genes are similar to that of a single Pax1/9 related gene
      in Branchiostoma lanceolatum, AmphiPax1. This supports the hypothesis that Pax1
      and Pax9 genes were derived from a single ancestral gene. A refined protein
      alignment of AmphiPax1, mouse Pax1 and human PAX9 proteins based on the
      determined exon boundaries indicates that sequence divergence at the C-termini
      may be related to the unique functions of the Pax1 and Pax9 genes in vertebrates.
      AmphiPax1 is expressed in adult amphioxus in the pharyngeal endoderm.

PMID- 10899595
TI  - Characterization and expression of the mouse pregnant specific uterus protein
      gene and its rat homologue in the intestine and uterus.
AB  - The pregnant specific uterus protein gene (Psup) is a novel mouse gene expressed
      in pregnant uterus. This paper describes the identification and expression of the
      rat homologue of Psup. The gene is highly expressed in the duodenum. Expression
      decreases in a proximal-distal gradient in the small intestine and was not
      detected in the cecum and colon. The pattern of expression in the mouse was
      similar. Expression of Psup in the mouse was localized to the epithelial cells in
      the intestine and pregnant uterus by in situ hybridization. The data show tissue
      specific expression of Psup.

PMID- 10899597
TI  - The 5S rRNA genes in Macaca fascicularis are organized in two large tandem
      repeats.
AB  - The 5S rRNA genes in Macaca fascicularis are organized in tandem repeats which
      are unusually large and complex. The tandem repeats consist of a 7.3 kb DNA
      fragment with two 5S rRNA genes linked to a 4.3 kb fragment with one gene. The
      total number of genes in the repeats is 50-100 per haploid genome. The 5S rDNA
      has an external promoter, the D box, in the same position relative to
      transcription start as the human gene but is transcribed less efficiently than a
      human 5S rRNA gene in a HeLa cell extract.

PMID- 10899598
TI  - Isolation of quail qMEF2D gene and its expression pattern in the developing
      central nervous system.
AB  - We report here the identification of the first avian MEF2 gene, termed qMEF2D.
      qMEF2D is the first MEF2 protein that contains 41 repeats of glutamine in the C
      terminal. This quail gene is more abundantly expressed, in a transient fashion,
      in the developing brain than in the muscle cells.

PMID- 10899599
TI  - Identification of a cDNA encoding an isoform of human CTP synthetase.
AB  - A full-length cDNA clone encoding an isoform of human CTP synthetase (type II)
      was isolated. A 1761-nucleotide open reading frame which corresponds to a protein
      of 586 amino acids with a predicted molecular mass of 65678 Da was identified.
      The predicted protein sequence showed 74% identity with the translation product
      of a previously identified human CTP synthetase cDNA clone (type I). The function
      of the human cDNA encoding type II CTP synthetase was verified by successful
      complementation of the cytidine-requiring CTP synthetase deficient mutant JF618
      of Escherichia coli. The gene encoding type II CTP synthetase has been localized
      on chromosome Xp22.

PMID- 10899600
TI  - Sequence and molecular analysis of the rpoA cluster genes from Xanthomonas
      campestris pv. campestris.
AB  - The Xanthomonas campestris rpsM (S13)-rpsK (S11)-rpsD (S4)-rpoA (alpha)-rplQ
      (L17) cluster, encoding RNA polymerase alpha-subunit and four ribosomal proteins,
      reside in a 3164-bp DNA region. The N-terminal sequence of the authentic alpha
      protein determined chemically matches that predicted from the nucleotide
      sequence. rplQ is monocistronic, instead of being co-transcribed with the other
      genes as in Escherichia coli. Antiserum against the His-tagged alpha-protein
      cross-reacted with the E. coli alpha-protein.

PMID- 10899602
TI  - Reverse transcriptase activity in bovine bone marrow: purification of a 66-kDa
      enzyme.
AB  - The presence of reverse transcriptase (RT) activity in a DNA-binding protein
      complex of the goat bone marrow has been reported earlier from our laboratory.
      Here we report a procedure for the purification of the enzyme with RT activity
      from bovine bone marrow and show that the basic function is associated with a
      approximately 66-kDa protein. This enzyme can use RT specific homopolymers as
      template and short oligonucleotides as primers, while displaying a Mg(2+)-ion
      requirement. Eukaryotic RTs have been shown to have endogenous RNAs associated
      with the enzymes. Evidence is presented here to show that some endogenous RNAs
      are associated with the RT activity in bovine bone marrow. Even though the enzyme
      activity appears to be associated with a approximately 66-kDa protein, the
      results indicate that for a full expression of its activity, the enzyme needs to
      interact with a 55-kDa protein that co-purifies with the enzyme during ion
      exchange chromatography.

PMID- 10899606
TI  - Temperature and salt effects on proteolytic function of turnip mosaic potyvirus
      nuclear inclusion protein a exhibiting a low-temperature optimum activity.
AB  - The nuclear inclusion protein a (NIa) of turnip mosaic potyvirus is a protease
      responsible for processing the viral polyprotein into functional proteins. The
      NIa protease exhibits an unusual optimum proteolytic activity at about 16 degrees
      C. In order to understand the origin of the low-temperature optimum activity, the
      effects of temperature and salt ions on the catalytic activity and the structure
      of the NIa protease have been investigated. The analysis of the temperature
      dependence of k(cat) and K(m) revealed that K(m) decreases more drastically than
      k(cat) as temperature decreases. The thermodynamic analysis showed that the
      decrease of K(m) is driven entropically, suggesting a possibility that the
      substrate binding might need a large entropy cost. The secondary structure of the
      NIa protease was significantly perturbed at temperatures between 20 and 40
      degrees C and the protease was unfolded at very low concentrations of guanidine
      hydrochloride with a transition midpoint of 0.8 M. These results suggest that the
      NIa protease is highly flexible in structure. Interestingly, salt ions including
      NaCl, KCl, CaCl(2) and MgCl(2) stimulated the proteolytic activity by 2-6-fold
      and increased the optimum temperature to 20-25 degrees C. This stimulatory effect
      of the salt ions was due to the lowering of K(m). The salt ions promoted the
      structural rigidity as evidenced in the higher resistance to the heat-induced
      unfolding in the presence of the salt ions. The increase in rigidity may lead to
      the lowering of K(m) possibly by reducing the entropic cost for substrate
      binding. Taken together, these results suggest that the NIa protease is highly
      flexible in structure and the low-temperature optimum activity might possibly be
      attributed to lowered entropy cost for substrate binding at lower temperatures.

PMID- 10899610
TI  - Conformational specificity of trigger factor for the folding intermediates of
      alpha-lactalbumin.
AB  - To understand the structural features of polypeptides recognized by trigger
      factor, a number of conformational derivatives of alphaLA were prepared and their
      effects on the trigger factor assisted refolding of GAPDH were investigated. It
      was found that the conformers of alphaLA that efficiently reduce the trigger
      factor assisted reactivation of guanidine-denatured GAPDH by competitively
      binding with trigger factor are those derivatives that have loose structure. This
      suggests that trigger factor binds mainly to intermediates formed early during
      folding of GAPDH.

PMID- 10899613
TI  - Characterization of an extracellular chymostatin-sensitive serine protease
      preferentially expressed in young plant tissues.
AB  - Intercellular washing fluids from leaves of all tested higher plant species
      contained a serine-type protease which efficiently cleaved the artificial
      fluorogenic substrate MCA-Pro-Leu-Gly-Leu-Dnp-Ala-Arg (MCA). The activity varied
      between the species. The classification as serine protease was based on the
      sensitivity towards chymostatin and phenylmethylsulfonyl fluoride. MCA protease
      activity strongly declined with leaf age and was also detected in stems, roots
      and flower petals. In tobacco, specific activity of the chymostatin-sensitive MCA
      protease was about 40-fold higher in intercellular washing fluids than in whole
      leaf homogenate confirming the extracellular location of the MCA protease. The
      same enzyme activity was detected in developing tomato fruits; it showed a
      correlation with fruit growth and was not detectable in ripe fruits. The tobacco
      protease was sensitive to temperatures above 50 degrees C, had an isoelectric
      point of 5.8+/-0.1 and an apparent molecular mass of 68 kDa. Its pH optimum was
      very broad with little difference in activity between pH 5 and 9. Conversely, a
      casein-cleaving protease also present in intercellular washing fluids was
      insensitive towards chymostatin and revealed a pronounced pH optimum around 6.0.
      The data biochemically characterize a new type of extracellular proteolytic
      activity which may be particularly important during tissue expansion.

PMID- 10899615
TI  - Expression and characterization of protein geranylgeranyltransferase type I from
      the pathogenic yeast Candida albicans and identification of yeast selective
      enzyme inhibitors.
AB  - Protein geranylgeranyltransferase type I (GGTase I) is a heterodimeric zinc
      metalloenzyme catalyzing protein geranylgeranylation at cysteine residues present
      in C-terminal signature sequences referred to as CaaX (X=Leu) motifs. We have
      studied GGTase I as a potential antifungal target and recently reported its
      purification and cloning from the yeast Candida albicans (Ca GGTase I), an
      important human pathogen. Here, we report the high yield bacterial expression of
      Ca GGTase I by coexpression of maltose binding protein fusion proteins of both
      the alpha (Ram2p) and beta (Cdc43p) subunits. The cleaved and purified
      recombinant Ca GGTase I was demonstrated to be functional and structurally intact
      as judged by the presence of one equivalent of a tightly bound zinc atom and the
      near stoichiometric formation, isolation and catalytic turnover of a
      geranylgeranyl pyrophosphate-GGTase I complex. Kinetic analysis was performed
      with a native substrate protein, Candida Cdc42p, which exhibited significant pH
      dependent substrate inhibition, a feature not observed with other Ca GGTase I
      substrates. Prenyl acceptor substrate specificity was studied with a series of
      peptides in which both the CaaX motif, and the sequence preceding it, were
      varied. The prenyl acceptor K(M)s were found to vary nearly 100-fold, with
      biotinyl-TRERKKKKKCVIL, modeled after a presumably geranylgeranylated Candida
      protein, Crl1p (Rho4p), being the optimal substrate. A screen for inhibitors of
      Ca GGTase I identified compounds showing selectivity for the Candida versus human
      GGTase I. The most potent and selective compound, L-689230, had an IC(50) of 20
      nM and >12,500-fold selectivity for Ca GGTase I. The lack of significant anti
      Candida activity for any of these inhibitors is consistent with the recent
      finding that GGTase I is not required for C. albicans viability [R. Kelly et al.,
      J. Bacteriol. 182 (2000) 704-713].

PMID- 10899618
TI  - A non-specific aminopeptidase from Aspergillus.
AB  - A fermentation broth supernatant of the Aspergillus oryzae strain ATCC20386
      contains aminopeptidase activity that releases a wide variety of amino acids from
      natural peptides. The supernatant was fractionated by anion exchange
      chromatography. Based on the primary amino acid sequence data obtained from
      proteins in certain fractions, polymerase chain reaction (PCR) primers were made
      and a PCR product was generated. This PCR product was used to screen an A. oryzae
      cDNA library from which the full length gene was then obtained. Fusarium
      venenatum and A. oryzae were used as hosts for gene expression. Transformed
      strains of both F. venenatum and A. oryzae over-expressed an active
      aminopeptidase (E.C. 3.4.11), named aminopeptidase II. The recombinant enzyme
      from both fungal hosts appeared as smears on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. After deglycosylation of the N-linked sugars,
      both samples were a sharp band at approximately 56 kDa and had identical N
      terminal amino acid sequences. Aminopeptidase II is a metalloenzyme with,
      presumably, Zn in the active site. Using various natural peptides and para
      nitroanilides (pNAs) of amino acids as substrates, the aminopeptidase was found
      to be non-specific. Only X-Pro bonds demonstrated resistance to hydrolysis
      catalyzed by this aminopeptidase. The optimal enzyme activity was observed at pH
      9.5 and 55 degrees C. Among amino acid pNAs, Leu-pNA appears to have the highest
      value of bimolecular constant of 40 min(-1) mM(-1) (k(cat) = 230 min(-1); K(m) =
      5.8 mM) at pH 7.5 and 21 degrees C. Among Xaa-Ala-Pro-Tyr-Lys-amide
      pentapeptides, the velocity of catalytic hydrolysis at pH 7.5 and 21 degrees C
      was in a decreasing order: Pro, Ala, Leu, Gly and Glu.

PMID- 10899626
TI  - Polynucleotide:adenosine glycosidase activity of saporin-L1: effect on various
      forms of mammalian DNA.
AB  - Saporin-L1 from the leaves of Saponaria officinalis belongs to a group of plant
      polynucleotide:adenosine glycosidases, known as ribosome-inactivating proteins
      due to their property of depurinating the major rRNA. Previous experiments
      indicated that saporin-L1 and other ribosome-inactivating proteins depurinate
      also DNA [Barbieri et al. (1994) Nature 372, 324; and (1996) Biochem. J. 319, 507
      513]. Here we describe the effects of highly purified nuclease-free saporin-L1 on
      mammalian nuclear and mitochondrial DNA. Saporin-L1 had less activity on
      mitochondrial DNA than on nuclear DNA. A low, although significant, depurination
      of both chromatin and whole nuclei was observed. Mitochondrial nucleic acids are
      heavily depurinated in intact mitochondria, although the contribute of mtDNA to
      the deadenylation events is not known. The kinetic constants for several
      substrates were determined.

PMID- 10899625
TI  - Angiotensin II generation by mast cell alpha- and beta-chymases.
AB  - Mast cells secrete alpha- and beta-chymases. Primate alpha-chymases generate
      angiotensin (AT) II by selectively hydrolyzing AT I's Phe(8)-His(9) bond. This is
      distinct from the AT converting enzyme (ACE) pathway. In humans, alpha-chymase is
      the major non-ACE AT II-generator. In rats, beta-chymases destroy AT II by
      cleaving at Tyr(4)-Ile(5). Past studies predicted that AT II production versus
      destruction discriminates alpha- from beta-chymases and that Lys(40) in the
      substrate-binding pocket determines alpha-chymase Phe(8) specificity. This study
      examines these hypotheses by comparing AT II generation by human alpha-chymase
      (containing Lys(40)), dog alpha-chymase (lacking Lys(40)), and mouse mMCP-4 (a
      beta-chymase lacking Lys(40); orthologous to AT II-destroying rat chymase rMCP
      1). The results suggest that human and dog alpha-chymase generate AT II
      exclusively and with comparable efficiency, although dog chymase contains Ala(40)
      rather than Lys(40). Furthermore, AT II is the major product generated by
      degranulation supernatants from cultured dog mast cells, which release tryptases
      and dipeptidylpeptidase as well as alpha-chymase. In contrast to rMCP-1, mMCP-4
      beta-chymase readily generates AT II. Although there is competing AT I hydrolysis
      at Tyr(4), mMCP-4 does not destroy AT II quickly once it is formed. We conclude
      (1) that chymases are the dominant AT I-hydrolyzing mast cell peptidases, (2)
      that residues other than Lys(40) are key determinants of alpha-chymase AT I
      Phe(8) specificity, (3) that beta-chymases can generate AT II, and (4) that alpha
      and beta-chymases are not strictly dichotomous regarding AT I cleavage
      specificity.

PMID- 10899627
TI  - Domain-specific spectroscopy of 5-hydroxytryptophan-containing variants of
      Escherichia coli DnaJ.
AB  - Tryptophan-containing variants of Escherichia coli DnaJ protein were constructed
      in order to examine the hypothetical domain structure by fluorescence quenching
      and denaturant-induced unfolding. Two residues in the J-domain and one in the
      Gly/Phe-rich region were targeted for replacement and the proteins were expressed
      in a tryptophan auxotrophic strain in the presence of 5-hydroxytryptophan (5-HW).
      Fluorescence quenching with iodide of 5-HW in the variant proteins suggests that
      the Gly/Phe-rich region is more accessible to solvent than the J-domain. This is
      consistent with the proposal that the Gly/Phe-rich region is unstructured.
      Unfolding of the 5-HW-containing variants was monitored by fluorescence, and the
      results showed that the unfolding of the J-domain is cooperative and the
      unfolding of the Gly/Phe-rich region is not cooperative.

PMID- 10899628
TI  - Enzyme activity down to -100 degrees C.
AB  - The activities of two enzymes, beef liver catalase (EC 1.11.1.6) and calf
      intestine alkaline phosphatase (EC 3.1.3.1), have been measured down to -97
      degrees C and -100 degrees C, respectively. Enzyme activity has not previously
      been measured at such low temperatures. For catalase, the cryosolvents used were
      methanol:ethylene glycol:water (70:10:20) and DMSO:ethylene glycol:water
      (60:20:20). For alkaline phosphatase, methanol:ethylene glycol:water (70:10:20)
      was used. All of the Arrhenius plots were linear over the whole of the
      temperature range examined. Since the lowest temperatures at which activity was
      measured are well below the dynamic transition observed for proteins, the results
      indicate that the motions which cease below the dynamic transition are not
      essential for enzyme activity. In all cases the use of cryosolvent led to
      substantial increases in Arrhenius activation energies, and this imposed
      practical limitations on the measurement of enzyme activity below -100 degrees C.
      At even lower temperatures, enzyme activity may be limited by the effect of
      solvent fluidity on substrate/product diffusion, but overall there is no evidence
      that any intrinsic enzyme property imposes a lower temperature limit for enzyme
      activity.

PMID- 10899632
TI  - Modulation of plasminogen activation and plasmin activity by methylglyoxal
      modification of the zymogen.
AB  - The effect of methylglyoxal on the plasminogen-plasmin system is studied.
      Treatment of plasminogen with methylglyoxal at a 20-fold molar excess results in
      covalent modification of the molecule as evidenced by the decreased number of
      NH(2) side chains, arginine side chain residues and the new band in the non
      tryptophan dependent fluorescent spectrum. This structural modification is
      associated with profound functional alterations: the rate of activation by
      streptokinase, tissue-type plasminogen activator, urokinase-type plasminogen
      activator and trypsin decreases and the amidolytic activity of the generated
      plasmin is impaired. Plasmin treatment with methylglyoxal on the other hand does
      not alter its steady-state kinetic parameters on a peptidyl-anilide synthetic
      substrate, indicating that modification susceptible side chains are sensitive to
      methylglyoxal only in the zymogen. Our data suggest that in vivo fibrinolysis
      could be impaired under pathological conditions, e.g. increased methylglyoxal
      formation in diabetes mellitus.

PMID- 10899633
TI  - Identical independent sites for dye ligand on bovine serum albumin demonstrated
      by multivariate analysis.
AB  - The most fundamental parameters concerning an interaction between a ligand and a
      protein are equilibrium constants and the number of binding sites. The Scatchard
      plot has for a long time been widely used to obtain those parameters. However,
      controversy in 1982-1983 over the reliability of this plot (the graphical
      estimation of the number of identical independent sites from the x-intercept)
      indicated that some methodologies other than the Scatchard plot are expected.
      Over the past decade, we have developed a method for applying multivariate
      analysis to the problem of determining spectral features of a ligand associated
      with a protein molecule. In principle, this method is based mainly on the
      computer-assisted adjustment of dissociation constants to an assumed reaction
      model. We discovered in this process that an n-parameter, introduced into an
      equation for calculating the amount of dye ligand bound to a protein, coincided
      with the number of identical independent sites, under a certain condition in
      principal factor analysis calculation. In this study, we established a new
      methodology for determining the number of identical independent sites using
      synthesized spectral series, and we then applied this method to a simple reaction
      system composed of bovine serum albumin (BSA) and bromocresol purple (BCP)
      anions. BSA was found to have two identical independent sites for BCP anions at
      pH 8.8.

PMID- 10899637
TI  - Why is creatine kinase a dimer? Evidence for cooperativity between the two
      subunits.
AB  - The dimeric chicken brain type isoenzyme of creatine kinase (BB-CK) was mutated
      by a C283S amino acid exchange in the catalytic site to produce a basically
      inactive dimer (B*B*-CK). The mutated enzyme showed a residual activity of about
      4% compared to the wild-type, whereas substrate binding parameters were not
      altered. The inactivated dimer was hybridized with native dimeric muscle enzyme
      (MM-CK) to produce a partially inactivated MB*-CK heterodimeric hybrid and also
      to a his-tagged BB-CK (hBhB-CK) resulting in a partially inactive hBB*-CK
      homodimer. The generated hybrids were purified by chromatography. The V(max) and
      substrate binding parameters K(m) and K(d) were determined for both directions of
      the CK reaction and compared to the parameters of the wild-type enzymes (MM-, BB
      , hBhB-, MB-CK). In the direction of ATP synthesis (reverse reaction), the MB*-
      and hBB*-CK hybrids showed a decrease of V(max) to 34% and 32%, respectively,
      compared to the unmodified wild-type isoform. The inactivation of a single
      subunit in MB*-CK led to an increase in the K(d) value resulting in an
      significant substrate synergism, not seen with the MB-CK wild-type enzyme. In the
      direction of phosphocreatine synthesis (forward reaction), the modified hybrids
      showed a decrease of V(max) to 50% of the wild-type enzymes and no significant
      alterations of the K(m) and K(d) parameters. These results strongly suggest an
      enzymatic cooperativity of the two subunits in the reverse reaction but
      independent catalytic function in the forward reaction.

PMID- 10899639
TI  - Protein kinases from Dictyostelium discoideum with similarity to LIM kinases.
AB  - We cloned a protein kinase (DdKinY) from Dictyostelium discoideum by low
      stringency hybridization using the catalytic domain from DdKinX [B.W. Wetterauer
      et al., Biochim. Biophys. Acta 1265 (1995) 97-101] as a probe. Both kinases have
      low sequence similarity to other protein kinases in the databases. However,
      phylogenetic analysis showed that both kinases cluster with vertebrate LIM
      kinases due to homology within the catalytic domain.

PMID- 10899641
TI  - All rights reserved, or can we just copy? Cost sharing arrangements and
      characteristics of health care systems.
AB  - In most European countries cost sharing has been introduced in order to reduce
      the demand for care. Different forms of cost sharing are available, but because
      of historically grown system characteristics and prevailing values countries
      differ in the application of specific forms. This review focuses on eighteen
      European countries, and on the combinations of health system characteristics and
      present forms of cost sharing. We found that some combinations are more present:
      different payment systems for primary care physicians go together with different
      forms of cost sharing, different services have different forms of cost sharing.
      In countries with a GP as gatekeeper no charges are in use for the GP. No
      distinct relationship could be found between the financing system (tax-based or
      insurance-based) and the form of cost sharing or the exclusion of vulnerable
      populations. It is concluded that there are two ways of filtering 'unnecessary'
      demand. One is by introducing cost sharing for directly accessible services such
      as GPs. The second way is by having GPs act as gatekeepers to more specialized,
      and more costly care.

PMID- 10899642
TI  - Maximum waiting time - a threat to clinical freedom? Implementation of a policy
      to reduce waiting times.
AB  - This article focuses on physicians as implementers of health policy reforms. In
      1992, a maximum waiting-time guarantee was introduced in Sweden. Initially the
      policy was a successful way to come to terms with long waiting times. However,
      after 2 years the waiting lists started to increase. To understand this
      development it is important to look at the reactions to the policy among the
      implementers, i.e. the physicians. Three questions are addressed: Did the
      implementers understand the intentions and the goals of the reform? Were they
      able to fulfil the guarantee? And, did they approve of the initiative? The study
      subjects were chief physicians at the hospital departments involved with the
      guarantee. Their attitudes towards the policy were ascertained by two surveys.
      Other material, such as statistics on waiting times, was also used. The study
      shows that the physicians approved of the guarantee initially. The measures taken
      in the first years were effective and did not conflict with earlier practice.
      However, increased demand in combination with economic restraints necessitated
      new priorities among patient groups. These changes of clinical practice did not
      coincide with the physicians' professional values and hence they became more
      critical to the initiative and finally chose to abandon the intentions in the
      guarantee.

PMID- 10899643
TI  - Gender and tuberculosis control: perspectives on health seeking behaviour among
      men and women in Vietnam.
AB  - This study explores the perspectives of tuberculosis patients on which factors
      influenced their health seeking behaviour, with special reference to gender
      differentials in terms of delays in health seeking. In 1996, a multi-disciplinary
      research team carried out 16 focus group discussions. The study was done in four
      districts in Vietnam, both in the south and north of the country and in urban and
      rural areas. Qualitative analysis of data was performed following general
      principles of modified grounded theory technique. Participants in the focus
      groups described three main factors as contributing to delay in health seeking.
      These were fear of social isolation, economic constraints and inadequate staff
      attitudes and poor quality of health services. A model illustrating different
      factors influencing health seeking was elaborated and served as a basis for
      discussion of the findings. The main factor contributing to delay among women was
      described as fear of social isolation from the family or the community. Stigma
      was described as closely related to contextual factors such as gender-roles,
      socio-economic status and level of education and seemed to be mediated via denial
      and concealment of tuberculosis diagnosis and disease, thus causing delay. The
      main factor contributing to delay among men was described as fear of individual
      costs of diagnosis and treatment. Staff attitudes and quality of health service
      facilities were described as not always corresponding to people's expectations of
      appropriate health services. Women saw themselves and were seen by others as
      being more sensitive than men to poor service conditions and staff attitudes. A
      typical feature of the described health seeking behaviour of men was that they
      neglected symptoms until the disease reached a serious stage, by which time they
      tended to go directly to public health services without first visiting private
      health practitioners. Women, on the other hand, were described as having a
      tendency to seek out private services and practice self-medication before seeking
      care at public services. In conclusion, there is a need for better understanding
      of behavioural factors and for developing strategies, that take these into
      account. Health workers need to better understand gender and social aspects of
      tuberculosis control, particularly aspects that influence the likelihood for
      achieving equity in diagnosis and cure.

PMID- 10899644
TI  - On hypothetical bias and calibration in cost-benefit studies.
AB  - Despite a sound foundation in economic welfare theory, willingness to pay (WTP)
      has not been used as a measure of benefits in economic evaluations of health and
      health care to the same extent as in other fields. Some have suggested that this
      is due to non-economists' reluctance to placing dollar values on the benefits of
      health care. However, another potential reason could be uncertainties about the
      validity of the WTP measure. In this paper, we outline the bias problems with the
      WTP method, and specifically focus on hypothetical bias; i.e. whether the WTP
      from hypothetical elicitation methods overstates the real WTP or not. This is
      done by examining the literature in this field, with emphasis on economic
      experiments where there is a greater possibility for comparison. The findings are
      that hypothetical WTP in general significantly overestimates real WTP, but that
      calibration methods to reduce or eliminate this difference are currently being
      developed. We conclude that while the area is still very much under development,
      there seem to be reasons to view the use of cost-benefit analysis as a reasonable
      alternative to the more common cost-effectiveness analysis.

PMID- 10899645
TI  - Identification of risk groups in hepatoblastoma--another step in optimising
      therapy.

PMID- 10899646
TI  - Prostate cancer screening: the problem of overdiagnosis and lessons to be learned
      from breast cancer screening.
AB  - Screening for prostate cancer is a relatively new procedure, still under
      experimental evaluation within prospective randomised trials. The design of
      prospective studies has been mainly based on the experience of other cancer
      screenings, particularly breast cancer, for which data of several controlled
      studies are available. Unfortunately, breast cancer is very different from
      prostate cancer, particularly for aspects such as early diagnosis and, thus the
      screening process, originally modelled on the basis of the lesson taught by
      breast cancer screening, needs continuous re-evaluation and adjustment, based on
      data which are now being produced from ongoing screening experiences. In this
      paper, we will consider the most controversial aspects of prostate cancer
      screening and compare prostate screening with breast cancer screening in order to
      promote a better understanding of the current problems and lessons to be learned.

PMID- 10899647
TI  - The role of meta-analyses in assessing cancer treatments.
AB  - The results of individual phase III cancer clinical trials are often inconclusive
      due to the overly optimistic size of treatment differences that are sought.
      Increased power and precision can generally be obtained if the data from several
      different trials studying the same or similar questions are analysed together.
      Individual patient data meta-analyses, which combine together the quantitative
      results from all properly randomised studies, provide an overall estimate of the
      size of treatment differences. Individual patient data meta-analyses have played
      an especially important role in breast and gastrointestinal tract cancers where
      many important questions have been addressed. Although meta-analyses have been
      subject to considerable criticism, individual patient data meta-analyses provide
      the best overall evidence of treatment effect in the absence of large-scale
      trials and have been instrumental in providing objective data that can be used in
      the design of new studies.

PMID- 10899648
TI  - Prevalence of complementary therapy use by women with breast cancer. A population
      based survey.
AB  - The study measured the prevalence and costs of complementary therapy use by women
      diagnosed with breast cancer in the South Thames NHS region. A postal
      questionnaire was sent to a sample of 1023 women from the Thames Cancer Registry
      who had been diagnosed with breast cancer in the previous 7 years. Just over a
      fifth (22.4%) had consulted a complementary practitioner in the previous 12
      months. Almost one third (31.5%) had done so since diagnosis. Almost pound17000
      had been spent on visits in the previous year. The women using complementary
      medicine after diagnosis were slightly younger, more educated and more likely to
      have used complementary medicine before their diagnosis than non-complementary
      medicine users. In conclusion, significant numbers of women are visiting
      complementary therapists for health reasons following a breast cancer diagnosis.
      The out of pocket costs per user, with notable exceptions, are modest. Use of
      practitioners of complementary therapies following diagnosis is a significant and
      possibly growing phenomenon.

PMID- 10899649
TI  - Prognosis and clinical presentation of BRCA2-associated breast cancer.
AB  - 54 female breast cancer patients from 22 families with BRCA2 germ line mutations
      from Sweden and Denmark were compared with 214 age- and date of diagnosis-matched
      controls identified among breast cancer patients from South Sweden. At diagnosis,
      BRCA2-associated cases were more often node-positive (N+). OR=1.9 (95% confidence
      interval (CI)=1.0-3.6; P=0.036), and were more often clinical stage IV: OR=4.6
      (95% CI=1.3-17; P=0.021) than the controls. Bilateral disease was also more
      common among the BRCA2-associated cases: OR=2. 4 (95% CI=1.1-5.3; P=0.027).
      Breast cancer-specific survival (BCSS) was significantly worse among the BRCA2
      associated cases: RR=2.0 (95% CI=1.2-3.4; P=0.010). When stage was corrected for
      in a multivariate analysis, BCSS was no longer significantly worse for the BRCA2
      associated cases: RR=1.6 (95% CI=0.85-3.1). The corresponding effect after
      correction for bilateral disease was: RR=1.8 (95% CI=1.0-3.1; P=0.034). The
      unfavourable prognosis in BRCA2-associated breast cancer seems, to a great
      extent, to be a consequence of the higher clinical stage at diagnosis. The
      increased presence of bilateral cancers appears to have less impact on survival
      in this group of hereditary breast cancer. Data presented here needs to be taken
      into account when counselling healthy carriers of BRCA2 germ line mutations.

PMID- 10899650
TI  - The role of cathepsin D and PAI-1 in primary invasive breast cancer as
      prognosticators and predictors of treatment benefit with adjuvant tamoxifen.
AB  - In the last few years there has been an increased interest in treatment
      predictive factors in breast cancer patients. The aim of the study was to analyse
      the role of cathepsin D and plasminogen activator inhibitor-1 (PAI-1) expression
      as independent prognosticators and to assess their predictive value with respect
      to tamoxifen treatment. This study comprises 1851 patients with primary breast
      cancer diagnosed during 1988-1992. Their median age was 62 years (range: 24-91).
      The end-point was distant disease recurrence-free interval. Adjuvant treatment
      with tamoxifen was given to 1136 patients (61%). The median follow-up time was 59
      months (range: 39-88). Cathepsin D content was shown to be a significant
      independent prognosticator in multivariate Cox analysis (P=0.02). The optimal cut
      off level was 10 fmol/mg protein, other cut-off levels did not improve the
      results. The level of cathepsin D also appeared to predict the benefit of
      tamoxifen among oestrogen receptor (ER)-positive patients although this result
      did not reach statistical significance (P=0.09). In a multivariate Cox analysis
      including 497 patients PAI-1 content was shown to be a significant independent
      prognosticator (P=0.003) but did not appear to predict the benefit of tamoxifen
      treatment. The optimal cut-off level appeared to be 3 ng/mg protein, which was
      close to the median value 2.5 ng/mg (range: 0-51). We conclude that cathepsin D
      is a significant independent prognosticator and may possibly also predict the
      benefit of tamoxifen amongst ER-positive patients. PAI-1 was also found to be a
      strong independent prognosticator but no treatment interaction with adjuvant
      tamoxifen was found.

PMID- 10899651
TI  - DNA adduct level in lung tissue may act as a risk biomarker of lung cancer.
AB  - Lung cancer is a leading cause of mortality in Taiwan. We hypothesised that high
      susceptibility to DNA damage in the target organ acts as a risk biomarker for the
      development of lung cancer. To verify this hypothesis, the aromatic/hydrophobic
      DNA adduct levels of non-tumorous adjacent lung tissues from 73 primary lung
      cancer patients and 33 non-cancer controls were evaluated by 32P-postlabelling
      assay. Wilcoxon rank sum test showed that DNA adduct levels in lung cancer
      patients (49.58+/-33.39 adducts/10(8) nucleotides) were significantly higher than
      those in non-cancer controls (18.00+/-15.33 adducts/10(8) nucleotides, P<0.001).
      The DNA adduct levels among lung cancer and non-cancer samples were not
      influenced by smoking behaviour and cigarette consumption. Our data also showed
      that the polymorphisms of cytochrome P4501A1 (CYP1A1) Msp1, glutathione S
      transferase M1 (GSTM1) and the combination of both genetic polymorphisms were not
      related to the DNA adduct levels. Interestingly, positive association between
      CYP1A1 protein expression and DNA adduct levels was found when CYP1A1 protein
      expression in lung specimens from lung cancer patients was examined by
      immunohistochemistry. Multivariate linear regression analysis indicated that the
      DNA adduct level was not associated with gender, smoking behaviour, or genetic
      polymorphisms of CYP1A1 and GSTM1. Moreover, multivariate logistic regression
      analysis showed that persons with high DNA adduct levels (>48.66 adducts/10(8)
      nucleotides) had an approximately 25-fold risk of lung cancer compared with
      persons with low DNA adduct levels (</=48.66 adducts/10(8) nucleotides). In
      conclusion, DNA adduct levels in lung tissue may be a more reliable lung cancer
      susceptibility biomarker than DNA adduct levels in leucocytes. In addition,
      higher susceptibility to DNA damage in lung cancer patients may partly play a
      role in the development of lung cancer.

PMID- 10899652
TI  - The growing teratoma syndrome: results of therapy and long-term follow-up of 33
      patients.
AB  - Growing teratoma syndrome (GTS) is defined as an increase in tumour size during
      or after chemotherapy for germ cell tumour (GCT), and only mature teratoma at
      histological analysis of the resected tumour specimen. Between 1985 and 1997, 30
      male patients fulfilling GTS criteria were included in the present study. 3
      female patients were also included but analysed separately. A mature teratoma
      component was found in 86% of the primary GCT. 3 male patients (10%) had a
      complication at diagnosis of GTS. One male patient (4%) having undergone complete
      resection (n=24) had a recurrent GTS, compared with all but 1 patient (83%) in
      whom resection was partial (n=6) (P<0.001). 2 (8%) and 3 (50%) male patients
      treated with complete and partial resection subsequently developed a malignant
      NSGCT respectively (P=0.01). 2 female patients treated with partial resection
      presented a recurrent GTS. One of them died of this recurrent GTS. GTS is an
      entity in its own right with respect to complications and the natural history of
      the disease. Complete surgical resection is the treatment of choice for GTS.

PMID- 10899653
TI  - The possible influences of B2A2 and B3A2 BCR/ABL protein structure on
      thrombopoiesis in chronic myeloid leukaemia.
AB  - The Philadelphia chromosome, t(9;22)(q34;q11) gives rise more frequently, in
      chronic myeloid leukaemia (CML), to two BCR/ABL chimeric transcripts differing
      only by the absence of 75 nucleotides and defined as b2a2 and b3a2 types,
      encoding two 210-kDa tyrosine kinase proteins differing only by the absence of 25
      amino acids coded by the b3 exon. In the present study the two transcripts,
      detected by RT-PCR in 88 consecutive unselected CML patients, were correlated
      with haematological findings at diagnosis and with the megakaryocyte size and
      frequency by morphometric evaluation of 45 bone marrow biopsies. The secondary
      structure prediction and hydrophobicity of the b2a2 and b3a2 type BCR/ABL protein
      were also obtained. The prediction results for the b3 exon amino acids using GOR
      IV and NnPredict methods showed a short beta strand corresponding to the
      hydrophobic portion of the peptide. Significantly higher values were found in the
      platelet count of patients carrying b3a2 transcripts. The megakaryocyte size and
      frequency in bone marrow biopsies did not show significant differences between
      the two groups of patients. Stratifying the patients on the basis of white blood
      cell (WBC) count below or above 100x10(9)/l we still had, in both groups, a
      significant difference in the platelet count between the b2a2 and b3a2 patients.
      The possible relationships between the structure of b2a2 and b3a2 types of
      BCR/ABL fused protein and thrombopoiesis are discussed.

PMID- 10899654
TI  - Variants of the long control region of human papillomavirus type 16.
AB  - Expression of the human papillomavirus (HPV) E6 and E7 oncogenes is regulated on
      the transcriptional level by specific protein-binding sites contained in the
      viral long control region (LCR). Sequence changes within the LCR region may have
      an impact on the transcription of viral oncogenes, possibly resulting in
      differences in the oncogenic potential of the virus. The present study was
      designed to determine the sequence variability of the LCR of HPV 16 and to assess
      whether certain LCR variants do correlate with the clinical outcome of the
      disease of the uterine cervix. The entire LCR segment of HPV 16 was analysed from
      37 cervical biopsy specimens derived from 28 women included in the Kuopio long
      term prospective follow-up study. The LCR sequence was identical with the
      reference sequence in six HPV 16 isolates. Overall, 14 different HPV 16 LCR
      variants were identified. One of the variants showed sequence variation typical
      of the Asian-American variant lineage of HPV 16, and all the other variants
      appeared to belong to the European variant group. The European variants exhibited
      low genetic diversity, and only five of these LCR variants contained nucleotide
      changes involving known or proposed binding sites for transcription factors. The
      variants with changes at nucleotide positions 7193 and 7521 was the most
      prevalent, accounting for almost 37% of infections. This variant (7193; 7521) has
      been previously demonstrated to have similar transcriptional activity compared
      with the reference isolate by Veress and colleagues J Gen Virol 1999, 80, 1035
      1043. The reference isolate, variant (7193; 7521) and variants with changes
      within transcription factor binding sites accounted for most of the infections,
      and no significant differences were found in the comparison of the distribution
      of these different LCR isolates in cases where the disease showed progression to
      severe cervical intraepithelial neoplasia (CIN) or carcinoma in situ (CIS).
      Notably, both the reference isolate and variant (7193; 7521) were also closely
      associated with infections showing more aggressive behaviour. According to the
      present findings, in European HPV 16 isolates, intratype genetic variation of the
      LCR region does not seem to be commonly responsible for differences in the
      pathogenicity of the virus and thereby for a risk of progressive infections.

PMID- 10899655
TI  - Quality of life in patients with metastatic breast cancer receiving either
      docetaxel or sequential methotrexate and 5-fluorouracil. A multicentre randomised
      phase III trial by the Scandinavian breast group.
AB  - The purpose of this study was to evaluate the effects of two alternative
      chemotherapy regimes on the quality of life (QoL) of patients with advanced
      breast cancer. In a multicentre trial, 283 patients were randomised to receive
      either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). QoL was
      assessed at baseline and before each treatment using the European Organization
      for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ
      C30). Initial compliance in the QoL study was 96% and the overall compliance 82%.
      QoL data were available for 245 patients (T 130 and 115 MF). Both treatment
      groups showed some improvement in emotional functioning during treatment, with a
      significant difference favouring the MF group at treatment cycles 5 and 6. In the
      T group, the scores on the other functional scales remained stable throughout the
      first six cycles. There were significant differences favouring the MF group on
      the social functioning scale at treatment cycle 6 and on the Global QoL scale at
      treatment cycles 5 and 6. On most symptom and single-item scales there were no
      statistically significant differences between the groups. However, at baseline,
      the T patients reported more appetite loss, at treatment cycles 2-4, the MF
      patients reported more nausea/vomiting, and at treatment cycle 6, the T patients
      reported more symptoms of fatigue, dyspnoea and insomnia. There were no
      statistically significant differences between the groups in the mean change
      scores of the functional and symptom scales. Interindividual variance was,
      however, larger in the T group. Differences in QoL between the two treatment
      groups were minor. Hence, given the expectancy of comparable QoL outcomes, the
      choice of treatment should be made on the basis of the expected clinical effect.

PMID- 10899656
TI  - Pretreatment prognostic factors for children with hepatoblastoma-- results from
      the International Society of Paediatric Oncology (SIOP) study SIOPEL 1.
AB  - The aim of this study was to investigate the prognostic significance of
      pretreatment patient and tumour characteristics for overall (OS) and event-free
      (EFS) survival in 154 children affected by hepatoblastoma (HB) in the first
      prospective liver tumour study run by the International Society of Paediatric
      Oncology. The pretreatment characteristics studied were age, alpha-fetoprotein,
      platelet count, histology; from radiology: intrahepatic tumour extension
      (PRETEXT), lung metastases, enlarged hilar lymph nodes, vena cava or extrahepatic
      vena porta tumour extension and tumour focality. Five-year OS was 75% (95%
      confidence interval (CI) 68-82%) and EFS 66% (95% CI 59-74%). Both were
      univariately associated with PRETEXT and the presence of metastases. Additionally
      tumour focality and enlargement of hilar lymph nodes at diagnosis were
      univariately associated with EFS. In multivariate analysis, PRETEXT was the only
      predictor of OS; PRETEXT and metastases were predictors of EFS. There is a need
      to investigate further these factors to confirm their validity.

PMID- 10899657
TI  - Paclitaxel exposure time determines the nature of the interaction with radiation
      in HeLa cells. the role of apoptosis.
AB  - The purpose of the present study was to investigate further the mechanisms
      underlying subadditive and superadditive interactions of radiation and paclitaxel
      treatments in vitro. The protocol studied was a fixed radiation treatment (7 Gy)
      followed either immediately or after a 10 h delay by paclitaxel treatment.
      Paclitaxel treatment was exposure to either a fixed dose of paclitaxel (10 nM)
      for varying time intervals up to 25 h, or varying doses of paclitaxel up to 20 nM
      for a fixed exposure time of 24 h. The cells used were HeLa. Cell survival was
      assessed by colony forming ability and apoptosis was measured by flow cytometry.
      The results show that when the paclitaxel exposure time was 24 h superadditive
      interactions were observed at all paclitaxel doses. A reasonable correlation
      between surviving fraction as measured by colony forming ability and apoptosis in
      the attached cells at the end of paclitaxel treatment was observed. The nature of
      the interaction of radiation and subsequent paclitaxel treatment is critically
      dependent on the duration of the paclitaxel treatment.

PMID- 10899658
TI  - Macromolecule uptake in human melanoma xenografts. relationships to blood supply,
      vascular density, microvessel permeability and extracellular volume fraction.
AB  - The uptake of albumin-Evans blue in human melanoma xenografts was studied and
      related to blood supply, vascular density, microvessel permeability and
      extracellular volume fraction in an attempt to identify transport barriers
      limiting the delivery of macromolecular therapeutic agents to tumours. Three
      melanoma lines (A-07, R-18, U-25) were included in the study. Tissue
      concentrations of albumin-Evans blue were determined by spectrophotometry. The
      [86Rb] uptake method was used to measure tumour blood supply. Vascular density
      was determined by stereological analysis of histological sections. Microvessel
      permeability was measured by using the indicator diffusion method. Contrast
      enhanced magnetic resonance imaging was used to measure tumour extracellular
      volume fraction. The fractional volume of the extracellular space governed the
      uptake of albumin-Evans blue in the tumours. The uptake of albumin-Evans blue in
      the extracellular space was primarily limited by transport in the vasculature and
      not by transport across the microvascular wall or the transport through the
      interstitium. Our study thus suggests that novel strategies for improving the
      delivery of macromolecular therapeutic agents to tumours should focus on
      enhancing the tumour blood supply, increasing the half-life of the therapeutic
      agent in the blood plasma and/or enhancing the volume of the extracellular space
      available to macromolecules rather than on increasing the permeability of the
      microvascular wall or improving diffusion conditions in the tumour interstitium.

PMID- 10899659
TI  - Initiation-development modelling of allelic losses on chromosome 9 in multifocal
      bladder cancer.
AB  - Multiple low-grade, low-stage superficial tumours were analysed for loss of
      heterozygosity (LOH) on chromosome 9 with 29 markers. Three consensus regions
      were found, one at 9p (9p21-22) and two at 9q (9q21-31 and 9q32-34). Phylogenetic
      trees were calculated for each patient using both designated chromosome 9 regions
      and, separately, using individual microsatellite data. Regional analysis
      suggested that multiple, equally important regions for bladder tumour initiation
      exist on chromosome 9. During the development of tumours all regions were
      eventually affected. The phylogenetic analyses with individual markers were used
      as molecular clocks to trace the ordering of tumours. The results were compared
      with the physical locations of the tumours and a hypothetical development model
      was built. These are novel approaches which, to our knowledge, have not been used
      before.

PMID- 10899660
TI  - Adenosine acts as an inhibitor of lymphoma cell growth: a major role for the A3
      adenosine receptor.
AB  - In this study, we demonstrated several mechanisms exploring the inhibitory effect
      of low-dose adenosine on lymphoma cell growth. Adenosine, a purine nucleoside
      present in plasma and other extracellular fluids, acts as a regulatory molecule,
      by binding to G-protein associated cell-surface receptors, A1, A2 and A3.
      Recently we showed that low-dose adenosine released by muscle cells, inhibits
      tumour cell growth and thus attributes to the rarity of muscle metastases. In the
      present work, a cytostatic effect of adenosine on the proliferation of the Nb2
      11C rat lymphoma cell line was demonstrated. This effect was mediated through the
      induction of cell cycle arrest in the G0/G1 phase and by decreasing the telomeric
      signal in these cells. Adenosine was found to exert its antiproliferative effect
      mainly through binding to its A3 receptor. The cytostatic anticancer activity,
      mediated through the A3 adenosine receptor, turns it into a potential target for
      the development of anticancer therapies.

PMID- 10899661
TI  - Hip deformities in walking patients with cerebral palsy.
AB  - Hip deformities in walking patients with cerebral palsy are rare. Nineteen
      diplegic and four hemiplegic patients with unilateral hip subluxation were
      studied to determine whether or not characteristic gait patterns could be
      identified. All were examined clinically and radiologically as well as undergoing
      observational and instrumented three dimensional gait analysis. Twenty one of the
      patients compensated for the subluxation with an ipsilateral trunk lean and
      contralateral pelvic drop. These patterns were quantified in the kinematic and
      kinetic variables measured. We conclude that hip abductor weakness should be
      considered as the cause of the deformity.

PMID- 10899662
TI  - Three dimensional preparatory trunk motion precedes asymmetrical upper limb
      movement.
AB  - Three-dimensional trunk motion, trunk muscle electromyography and intra-abdominal
      pressure were evaluated to investigate the preparatory control of the trunk
      associated with voluntary unilateral upper limb movement. The directions of
      angular motion produced by moments reactive to limb movement in each direction
      were predicted using a three-dimensional model of the body. Preparatory motion of
      the trunk occurred in three dimensions in the directions opposite to the reactive
      moments. Electromyographic recordings from the superficial trunk muscles were
      consistent with preparatory trunk motion. However, activation of transversus
      abdominis was inconsistent with control of direction-specific moments acting on
      the trunk. The results provide evidence that anticipatory postural adjustments
      result in movements and not simple rigidification of the trunk.

PMID- 10899663
TI  - Significance of load receptor input during locomotion: a review.
AB  - A basic aspect of the neuronal control of quadrupedal locomotion of cat and of
      bipedal stance and gait of humans concerns the antigravity function of leg
      extensors. In humans proprioceptive reflexes involved in the maintenance of body
      equilibrium depend on the presence of contact forces opposing gravity. Extensor
      load receptors are thought to signal changes of the projection of body's centre
      of mass with respect to the feet. According to observations in the cat, this
      afferent input probably arises from Golgi tendon organs and represents a newly
      discovered function of these receptors in the regulation of stance and gait. From
      these experiments it can be concluded that during locomotion there is a closing
      of Ib inhibitory and an opening of Ib extensor facilitatory paths. In humans
      evidence for a significant contribution of load receptor contribution to the leg
      muscle activation came from immersion experiments. Compensatory leg muscle
      activation depends on the actual body weight. Also during gait the strength of
      leg extensor activation during the stance phase is load dependent. In patients
      with Parkinson's disease there is a reduced load sensitivity and decreased leg
      extensor activation, which might contribute to the movement disorder. Recent
      experiments in paraplegic patients show that the beneficial effects of a
      locomotor training critically depends on the initial degree of body unloading and
      reloading during the course of the training period.

PMID- 10899664
TI  - Desperately seeking synergy: the journey to systems integration of women's health
      services.
AB  - Providing women's health services can be a profitable enterprise. With 70% of
      health care purchases being made by women for themselves and their families,
      focusing on women as health care consumers strengthens the entire system.
      However, shrinking reimbursement and market pressures are creating an atmosphere
      of financial instability in health care. Is system integration the answer? The
      four presenters-each an executive champion for the women's service line in their
      systems-agree that integration can potentially reduce costs, improve quality of
      care, and increase patient and stakeholder satisfaction. Benefits can only be
      realized, however, if clinicians are engaged as partners early in the process,
      the organization is prepared to respond quickly to market changes, and
      competitive forces and culture differences across the system are acknowledged and
      addressed. "Women's Services" must also continually demonstrate its value to the
      system and find creative ways to differentiate itself in the marketplace.

PMID- 10899665
TI  - Quality and outcomes of care for older women with chronic disease.
AB  - This is the fourth in a series of six papers that will be published from the 1999
      lecture series on "Quality Assessment in Women's Health Care" held at the
      University of Michigan School of Public Health. The lectures are presented by
      leaders in women's health research, and they explore key issues in the
      definition, measurement, and improvement of quality in women's health services.
      The series is supported by an unrestricted educational grant from Pfizer Inc. and
      is presented by the Interdepartmental Concentration in Reproductive and Women's
      Health at the University of Michigan School of Public Health; the University of
      Michigan National Center of Excellence in Women's Health; and the Michigan
      Initiative for Women's Health. The series coordinator is Carol S. Weisman, PhD,
      and Catherine L. Maroney prepared the summary of the discussants' comments.

PMID- 10899666
TI  - Outcome assessment in women's mental health.
AB  - This is the fifth in a series of six papers that will be published from the 1999
      lecture series on "Quality Assessment in Women's Health Care" held at the
      University of Michigan School of Public Health. The lectures are presented by
      leaders in women's health research, and they explore key issues in the
      definition, measurement, and improvement of quality in women's health services.
      The series is supported by an unrestricted educational grant from Pfizer Inc. and
      is presented by the Interdepartmental Concentration in Reproductive and Women's
      Health at the University of Michigan School of Public Health; the University of
      Michigan National Center of Excellence in Women's Health; and the Michigan
      Initiative for Women's Health. The series coordinator is Carol S. Weisman, PhD,
      and Catherine L. Maroney prepared the summary of the discussants' comments.

PMID- 10899667
TI  - Women's health problems in soap operas: a content analysis.
AB  - A content analysis of women's health problems in network daytime serials is
      reported. Results indicate a preponderance of such problems as substance abuse,
      falls resulting in death or injury, comas or unconsciousness, mental health
      concerns (most notably represented by amnesia and multiple personality), concerns
      about AIDS, automobile accidents, being drugged, fainting, pregnancy problems,
      and violent acts resulting in harm. Such concerns as breast and cervical cancer
      and heart disease are less frequently portrayed.

PMID- 10899668
TI  - Knowledge and preference for breast conservation therapy among women without
      breast cancer.
AB  - We interviewed 419 adult women in Minnesota, who were selected at random and
      without a history of breast cancer, to ascertain what percentage could correctly
      report that cure was the same for breast conservation therapy and mastectomy,
      what percentage would state a preference for breast conservation therapy rather
      than mastectomy, and characteristics associated with these outcomes. Nearly all
      women (n = 360; 86%) had heard of both mastectomy and breast conservation
      therapy; among these women, 37% correctly reported that the two treatments were
      equally efficacious. Given a scenario where they were diagnosed with breast
      cancer amenable to either treatment, 58% of participants stated a preference for
      breast conservation therapy. Older women were less likely than younger women to
      know that cure was the same for breast conservation therapy and mastectomy
      (adjusted OR = 0.5, 95% CI 0.2, 1.0), and women residing in urban areas were more
      likely to prefer breast conservation therapy over mastectomy compared to rural
      residents (adjusted OR = 2.2, 95% CI 1. 3, 3.8). Comparing these findings to
      women diagnosed with breast cancer in Minnesota, breast conservation therapy was
      found to be performed less frequently than preference for such therapy among
      women in our study would suggest. Educating women prior to diagnosis about breast
      cancer treatment options, and exploring reasons for the gap between actual
      utilization of breast conservation therapy and prediagnosis preference, may be
      indicated.

PMID- 10899669
TI  - Genetic aberrations in oral or head and neck squamous cell carcinoma 2:
      chromosomal aberrations.
AB  - Carcinogenesis is the result of a series of genetic mutations resulting in
      unregulated growth of a clone of cells and the development of malignant lesion
      that is largely monoclonal though, with the evolution of further genetic changes,
      there develops a degree of heterogeneity in the tumour. DNA technology,
      especially allelic imbalance (loss of heterozygosity) studies have identified
      chromosomal changes in oral carcinoma and head and neck squamous cell carcinoma
      (SCCHN), suggestive of the involvement of tumour suppressor genes (TSGs),
      particularly in chromosomes 3, 9, 11 and 17. The regions most commonly identified
      have included 3p, especially 3p14.2 (FHIT); 3p24, and 3p21.3, where the TSGs
      involved are as yet unidentified; 9p21 where p16 (INK4A/MTS-1] is the main target
      TSG; and 17p13 where p53 is the major target TSG. Over-expression of oncogenes,
      genes mainly involved in cell signalling, especially those on chromosome 11 (PRAD
      1 in particular) and 17 (H-ras) and mutations in DNA repair genes, have also been
      implicated in the carcinogenesis of SCCHN.

PMID- 10899670
TI  - Is alcohol responsible for more intra-oral cancer?
AB  - The role of the major risk factors, tobacco smoking and alcohol consumption, on
      trends in intra-oral cancer mortality in England and Wales between 1911 and 1990
      was investigated, using lung cancer and liver cirrhosis as surrogate markers for
      smoking and drinking. Standardised mortality data on lung cancer and liver
      cirrhosis from the Office of Population Censuses and Surveys, aggregated into 5
      year time periods for ages 35-64 and 65+ years, were regressed on corresponding
      data for intra-oral cancer. The strongest associations were in males aged 35-64
      with a high negative correlation between lung and intra-oral cancer (rho=-0.98,
      95% CI -0.99 to -0.96, P<0. 01) and, conversely, a positive correlation between
      liver cirrhosis and intra-oral cancer (rho=0.71, 95% CI 0.34 to 0.89, P<0.01).
      The findings suggest that rising alcohol consumption since the 1950s is more
      closely related to increasing intra-oral cancer incidence and mortality than
      smoking, most notably among younger males since the early 1970s.

PMID- 10899671
TI  - Alterations of p53, pRb, cyclin D(1) and cdk4 in human oral and pharyngeal
      squamous cell carcinomas.
AB  - Alteration of expression of tumour suppressor genes and cell cycle regulators may
      be responsible for oral and pharyngeal cancer development. We have studied the
      expression of p53, pRb, cyclin D(1) and cdk4 in 53 cases of oral and pharyngeal
      squamous cell carcinomas using immunohistochemistry. Tumour expression of all
      nuclear proteins was scored according to the percentage of positive cancer
      nuclei. Positive p53 expression was detected in 27/53 (50.94%) cases. Lack of pRb
      immunostaining was observed in 39/53 (73.58%) cases. Overexpression of cyclin
      D(1) was shown in 21 (39.62%) tumours. The overexpression of cdk4 was detected in
      43/53 (81.13%) cases. There was no significant association among these cell cycle
      regulatory proteins. This implies that the aberration of an important cell cycle
      regulator may be sufficient to disrupt regulatory mechanism in a manner favouring
      tumourigenesis. In summary, our results suggest that inappropriate expression of
      p53, pRb, cyclin D(1) or cdk4 is likely to contribute to the development of oral
      and pharyngeal cancers. The lack of pRb expression and/or overexpression of cdk4
      play a crucial role in the development of this malignancy.

PMID- 10899672
TI  - Outcome following a population screening programme for oral cancer and precancer
      in Japan.
AB  - The purpose of this study was to evaluate the validity and outcome of an oral
      mucosal screening programme conducted in Japan. All adults over the age of 40
      years resident in Tokoname city were invited by letter to attend a free general
      health screen and oral examinations annually. Twenty- to 39-year-old females were
      also encouraged to participate. During the years 1996-98, a total of 19056
      subjects (5885 male, 13171 female: mean age 60.7+/-11.3 years) were examined by
      three types of screeners: postgraduate dental residents (n=17), hospital dentists
      (n=5) and general dental practitioners (n=15). In the cohorts examined screening
      dentists recorded oral mucosal lesions in 783 (4.1%) subjects. Of those detected
      with mucosal lesions, 200 (25.5%) were referred and 137 (68. 5%) attended for
      follow up examination in hospital departments by specialists with full diagnostic
      back up facilities. Thirty-nine subjects were confirmed as having oral cancer or
      precancer (two squamous cell carcinomas, 37 leukoplakias) and 40 with lichen
      planus. Five false positives (3.6%) were found. Among the cases referred under
      other diagnostic labels no cancers were detected. Among those who attended for
      confirmation of oral cancer or precancer by a specialist, sensitivity,
      specificity and positive predictive value were 0.92, 0.64 and 0.78, respectively.
      In males with oral cancer/leukoplakia, the prevalence of smoking, drinking and
      combined habits was higher than those with lichen planus or among negative
      subjects. The sensitivity and specificity determined from this research suggests
      that the performance of the Japanese dentists employed in screening was
      satisfactory. An attendance of 68% for re-examination by specialists compares
      well with other reported studies measuring patient compliance.

PMID- 10899673
TI  - Telomerase activity in oral and maxillofacial tumors.
AB  - Telomerase activity was measured in biopsy specimens as well as surgically
      resected tissues of 39 oral squamous cell carcinomas (SCCs), 22 oral
      leukoplakias, 13 normal oral mucosas, 12 malignant salivary gland tumors, 10
      benign salivary tumors and five normal salivary gland tissues adjacent to tumors
      using a polymerase chain reaction (PCR)-based telomerase assay. Telomerase
      activity was detectable in 38.5% (5/13) of normal oral mucosa samples, 54.5%
      (12/22) of leukoplakia samples, 82.1% (32/39) of oral SCC samples, 83.3% (10/12)
      of malignant salivary gland tumor samples and 0% (0/10, 0/5) of benign salivary
      gland tumor and normal salivary gland samples. High-level enzyme activities were
      seen in 20% (3/15) of mild dysplasia specimens, 50% (2/4) of moderate-severe
      dysplasia specimens, 48.7% (19/39) of oral SCC tissue specimens, and no high
      activity was seen in the normal mucosa and hyperkeratosis specimens (P for trend,
      <0.001). We also analyzed the proliferative activity of dysplastic leukoplakia,
      oral SCC, and salivary gland tumor specimens using Ki-67 immunohistochemistry.
      The Ki-67 labeling indices (LI) were significantly higher in dysplastic
      leukoplakia and oral SCC with high telomerase activity than in dysplastic
      leukoplakias and oral SCC with low and negative telomerase activity (P<0.01 and
      P<0.05). These results indicate that telomerase activity has some correlation
      with the progression of multistep oral carcinogenesis with the cellular
      proliferation, and also indicate that telomerase may be a specific marker used to
      distinguish malignant salivary gland tumors from their benign counterparts.

PMID- 10899674
TI  - Expression of proliferating cell nuclear antigen (PCNA) in oral submucous
      fibrosis, oral epithelial hyperkeratosis and oral epithelial dysplasia in Taiwan.
AB  - To test whether the oral epithelia of oral submucous fibrosis (OSF), epithelial
      hyperkeratosis (EH) and epithelial dysplasia (ED) may have increased
      proliferative activity under the long-term exposure to areca quid ingredients and
      whether there is an increased expression of proliferating cell nuclear antigen
      (PCNA) in oral premalignant lesions with disease progression, we used an
      immunohistochemical technique with the mouse monoclonal antibody PC10 to
      investigate PCNA expression in histologic sections of OSF, EH, ED and normal oral
      mucosa (NOM). Positive PCNA staining was found mainly in basal and parabasal
      epithelial cells in all specimens of OSF, EH, ED and NOM. The mean PCNA labeling
      indices (LI) in NOM, OSF, EH and ED were 8.8+/-2.7%, 22.1+/-12.5%, 25.5+/-5. 2%
      and 44.9+/-15.4%, respectively. Significant differences in the PCNA LI were noted
      between NOM and OSF (P<0.01), EH (P<0.001) or ED (P<0.001), as well as between ED
      and OSF (P<0.001) or EH (P<0.01). The gradual increase of PCNA expression with
      the morphologic transformation of normal epithelial cells into dysplastic
      epithelial cells suggests that there is increased proliferative activity in oral
      premalignant lesions with disease progression. However, no significant
      correlation was found between PCNA LI in OSF epithelium and the clinicohistologic
      parameters of OSF. In addition, the mean PCNA LI of p53-positive OSF cases
      (23.7+/-12.0%) was very close to that of p53-negative OSF cases (23.9+/-13.1%),
      suggesting that there was no association between PCNA and p53 expression in OSF.

PMID- 10899675
TI  - Salivary gland carcinosarcoma: immunohistochemical, molecular genetic and
      electron microscopic findings.
AB  - Salivary gland carcinosarcoma, or true malignant mixed tumor, is a very rare and
      extremely aggressive neoplasm. The clonality and clonal origin of this tumor are
      discussed controversially. We report a carcinosarcoma of the left parotid gland
      in a patient who subsequently died of cutaneous, lymphatic and pulmonary
      metastases. Immunohistochemical staining, electron micrograph analysis, loss of
      heterozygosity (LOH) analysis and sequence analysis were performed on this tumor
      with an adenocarcinomatous and a predominant spindle cell-like component. While
      smooth muscle actin was undetectable by immunohistochemistry, cytoplasmatic
      myoepithelial structures could be detected by electron microscopy. LOH analysis
      at 12 genomic locations detected complete deletion of one allele at 17p13.1,
      17q21. 3, and 18q21.3 indicating allelic loss in both components of the tumor.
      Double strand sequencing of the remaining allele of the p53 tumor suppressor gene
      revealed a wild-type allele. Based on our results, we favor the hypothesis of
      monoclonal origin of this salivary gland carcinosarcoma with a common stem cell
      that could be the myoepithelial cell and an inactivated tumor suppressor gene on
      chromosome 17 other than p53.

PMID- 10899676
TI  - Type I collagen degradation by invasive oral squamous cell carcinoma.
AB  - Expression of extracellular matrix-degrading proteases is required for tumor cell
      invasion. In the present study we examined the production of type I collagen
      degrading matrix metalloproteinases (MMPs) in the invasive oral squamous cell
      carcinoma-derived cell line HSC-3. In the absence of serum or exogenous growth
      factors, HSC-3 cells displayed no collagen degradation activity. Addition of
      serum slightly increased collagen proteolysis. However, addition of epidermal
      growth factor (EGF) resulted in nearly complete degradation of the collagen
      matrix. Zymography showed that MMP-2 and -9 are secreted by HSC-3 cells. EGF
      stimulated secretion of an additional gelatinase with a molecular weight similar
      to that of MMP-1. Immunoblotting of conditioned medium confirmed that EGF and, to
      a lesser degree type I collagen, increased production of MMP-1. Finally, in situ
      hybridization revealed intense expression of MMP-1 in oral squamous cell
      carcinoma specimens. Together, these results indicate that MMP-1 is expressed,
      induced by EGF, and required for type I collagen degradation in oral squamous
      cell carcinoma.

PMID- 10899677
TI  - Defining mechanisms of action of interleukin-11 on the progression of radiation
      induced oral mucositis in hamsters.
AB  - Oral ulcerative mucositis is a common toxicity associated with drug and radiation
      therapy for cancer. It impacts on quality of life and economic outcomes, as well
      as morbidity and mortality. Mucositis is often associated with dose limitations
      for chemotherapy or is a cause for dose interruption for radiation. The
      complexity of mucositis as a biological process has only been recently
      appreciated. It has been suggested that the condition represents a sequential
      interaction of oral mucosal cells and tissues, pro-inflammatory cytokines and
      local factors such as saliva and the oral microbiota. The recognition that the
      pathophysiology of mucositis is a multifactorial process was partially suggested
      by the observation that interleukin-11 (IL-11), a pleotropic cytokine, favorably
      altered the course of chemotherapy-induced mucositis in an animal model. In the
      current study, we evaluated a series of biologic and morphologic outcomes to
      determine their roles and sequence in the development of experimental radiation
      induced mucositis and to evaluate the effects of IL-11 in attenuating them. Our
      results suggest that IL-11 favorably modulates acute radiation-induced mucositis
      by attenuating pro-inflammatory cytokine expression. Data are also presented
      which help define the pathobiological sequence of mucositis.

PMID- 10899678
TI  - Inhibition of 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch
      carcinogenesis by S-allylcysteine.
AB  - Consumption of garlic has been reported to be associated with decreased risk of
      cancer. We used the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal
      pouch carcinoma model to assess the oral chemopreventive potential of S
      allylcysteine (SAC), a water-soluble constituent of garlic. Hamsters were divided
      into four groups of six animals each. The right buccal pouches of the animals in
      group I were painted with a 0.5% solution of DMBA in liquid paraffin three times
      a week. The animals in group II were painted with DMBA as in group I and in
      addition received 200 mg/kg body weight SAC intragastrically three times a week
      on days alternate to DMBA application. Group III animals received SAC as in group
      II. Animals in group IV received neither DMBA nor SAC and served as control. The
      hamsters were killed after an experimental period of 14 weeks. Biochemical
      measurements were carried out on tumour and normal pouch tissues. Measurement of
      lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (GPx) and
      glutathione S-transferase (GST) was used to monitor the chemopreventive potential
      of SAC. All hamsters painted with DMBA alone for 14 weeks developed well
      differentiated squamous cell carcinomas. Diminished lipid peroxidation in the
      oral tumour tissue was accompanied by a significant increase in the levels of
      GSH, GPx and GST. Administration of SAC significantly suppressed DMBA-induced
      oral carcinogenesis as revealed by the absence of neoplasms. The results of the
      present study suggest that garlic may exert its chemopreventive effects by
      modulating lipid peroxidation and enhancing the levels of GSH, GPx and GST.

PMID- 10899679
TI  - Increasing incidence of oral cancer amongst young persons: what is the aetiology?
AB  - The reasons for an increasing incidence of oral cancer, particularly amongst
      younger persons is unclear. It has been hypothesised either to be a result of an
      increase in exposure to known risk factors amongst certain groups in the
      community, or to be due to new aetiological agents. Prior to conducting large
      expensive population-based studies, it seems appropriate to conduct initial
      smaller-scale surveys to assess evidence for each of these two hypotheses. This
      survey of young persons with oral cancer suggest that most are exposed to
      traditional risk factors of tobacco smoking, drinking alcohol and a low
      consumption of fruit and vegetables.

PMID- 10899680
TI  - Paraneoplastic pemphigus caused by an epithelioid leiomyosarcoma and associated
      with fatal respiratory failure.
AB  - A patient is described who initially presented with pemphigus vulgaris, limited
      to the oral cavity, and weight loss. Although the various laboratory studies
      pointed to the diagnosis of paraneoplastic pemphigus (PNP), the underlying
      neoplasm was not detected until 6 months later, when the patient developed
      shortness of breath and routine physical examination on admission revealed an
      abdominal mass, which eventually was proven to be an epithelioid leiomyosarcoma.
      In spite of radical excision of the tumour and intensive treatment of the
      dyspnoea, the patient died of respiratory failure 19 months after the PNP had
      been diagnosed. Early diagnosis of PNP is stressed to possibly prevent fatal
      pulmonary involvement.

PMID- 10899681
TI  - "P53 tumor suppressor gene as a clonal marker in head and neck squamous cell
      carcinoma: P53 mutations in primary tumor and matched lymph node metastases" by
      G.W.A. Tjebbes Et al. Oral oncology 35, pp 384-389

PMID- 10899682
TI  - Hyperacute xenorejection of guinea pig-to-rat lung transplantation can be
      attenuated by blood which has perfused another xenograft.
AB  - In discordant xenotransplantation, the recipientOs blood initiates hyperacute
      xenorejection (HXR). We hypothesized that HXR-related lung edema may be reduced
      if a new xenograft is perfused by blood which previously has perfused another
      xenograft. In a syngeneic control group (n = 6), a rat lung (lung XR) was
      perfused by rat blood (blood AR), following which the blood was collected (blood
      BR). After another rat lung (lung YR) was perfused by blood BR, the blood was
      collected (blood CR). In a xenogeneic experimental group (n = 6), a guinea pig
      lung (lung XG) was perfused by rat blood (blood AG), and the blood was collected
      (blood BG). Then, another guinea pig lung (lung YG) was perfused by blood BG, and
      once more the blood was collected (blood CG). White blood cells (WBC),
      polymorphonuclear leukocytes (PMN), red blood cells (RBC), hemoglobin,
      hematocrit, and complement (CH50) in the blood were measured pre- and post
      perfusion. The wet/dry weight ratio (W/D) of the lung was calculated after the
      perfusion. WBC and PMN were higher in blood CR/BR than in blood BR/AR. CH50 was
      higher in blood CG/BG than in blood BG/AG. RBC, hemoglobin, and hematocrit were
      not different among the blood AR, BR, CR, AG, BG, and CG. The W/D was not
      different between lung XR and lung YR. The W/D of lung YG was lower than lung XG.
      In conclusion, the lung edema associated with HXR is reduced when blood which has
      perfused another xenograft is used to perfuse the new xenograft without anemia,
      and complement plays a critical role in reducing lung edema.

PMID- 10899683
TI  - Prevention of postoperative intrapleural adhesion of the thoracotomy incision by
      a bioresorbable membrane in the rat adhesion model.
AB  - For the purpose of reducing the risk of lung injury while separating adhesions in
      repeated pulmonary resections, the inhibitory effect of hyaluronate based
      bioresorbable membrane (HA membrane) on postoperative adhesions was investigated
      in a new pleural adhesion model in rats. First of all, a novel post-thoracotomy
      adhesion model in rats was successfully established by using a combination of
      mechanical, chemical and ischemic injuries of the pleura during operation. After
      undergoing the same adhesion-inducing procedures, one of two groups was treated
      with HA membrane inserted between the lung and the parietal pleura, and the other
      group underwent infusion of saline only. The severity of the adhesion formation
      was macroscopically lower in the HA membrane-treated rats, and they had favorable
      mesothelial regeneration microscopically. Additionally, the activity of type 1
      plasminogen activator inhibitor (PAI-1) in the intrapleural lavage fluid (ILF)
      was measured at 24 hours postoperatively because this is the main influence on
      adhesion formation after surgery. PAI-1 activity was 23.37+/-2.57 U/ml in the
      saline-treated group and 17.85+/-3.06 U/ml in the HA membrane-treated group. The
      result suggests that the HA membrane inhibits postoperative adhesion formation
      through a significant repression of PAI-1 activity.

PMID- 10899684
TI  - Permanent cardiac pacing following surgery for acquired valvular disease.
AB  - Between January 1980 and January 1998, implantation of a permanent pacemaker (PP)
      was performed in 22 patients (6.7%) following 327 acquired valvular surgeries.
      The indications for implantation of a PP were bradycardia with atrial
      fibrillation in 12 cases, sick sinus syndrome in 7 cases and complete
      atrioventricular block in 3 cases. These patients received an implantation after
      surgery for mitral valvular disease in 14 cases, aortic valvular disease in 3
      cases and combined valvular disease in 5 cases. These cases were also concomitant
      with a tricuspid valve annuloplasty in 6 cases for secondary regurgitation and
      with a maze procedure in 4 cases. For the purpose of this study, these patients
      were compared to patients who did not require implantation of a PP after surgery.
      Univariate analysis showed the significant factors to be female gender (p = 0.
      041), preoperative atrial fibrillation (p = 0.013), redo cardiac surgery (p <
      0.0001), and the use of blood cardioplegia (p = 0.003). There were no differences
      in valvular disease, age at the last valvular operation, addition of tricuspid
      valve annuloplasty, extracorporeal circulation times, or aortic cross-clamp times
      between those patients with and those without PP. Among these factors, logistic
      regression analysis showed female gender, redo surgery and the use of blood
      cardioplegia to be more significant predictors for the requirement of PP after
      acquired valvular disease operation. Maze procedure was not a significant
      predictor for the requirement of PP after surgery.

PMID- 10899685
TI  - Quality of life in patients over 70 years of age after heart valve replacement.
AB  - BACKGROUND: Previous studies on valve replacement in patients over 70 years of
      age have been concerned with early and long-term outcome. Little is known,
      however, of the quality of life (QOL) of survivors following surgery. METHODS:
      Thirty-one consecutive patients, mean age 74.0+/-3.1 years, who underwent heart
      valve replacement were reviewed and questioned as to their physical and social
      activities before and after surgery and compared with 75 patients aged less than
      70 years old who underwent similar procedures during the same time interval. QOL
      was measured by using the Rosser distress and disability scores. RESULTS:
      Hospital mortality in the elderly group was the same as in the younger group
      (9.7% vs 2.7%, p = 0.121). Median 5-year survival was 79% in the elderly group
      and 92% in the younger group (p = 0.068). Overall morbidity due to valve-related
      complications was 3.55%/patient-year in the elderly group and 2. 35%/patient-year
      in the younger group, and freedom from all valve-related complications at 5 years
      was 76%, and 83%, respectively (p = 0.202). There were significant improvements
      in the distress and disability scores postoperatively (mean interval: 32. 4+/
      20.4 months). The QOL value rose from 0.960 to 0.981 in the elderly group (p =
      0.0004), and from 0.975 to 0.984 in the younger group (p = 0.07), suggesting that
      the magnitude of improvement in the elderly group was superior to that in the
      younger group. CONCLUSIONS: Heart valve replacement in patients over the age of
      70 years was associated with reasonable early and mid-term morbidity. We believe
      that significant improvements in the symptoms, functional status, and QOL of the
      patients can be expected.

PMID- 10899686
TI  - Coronary artery bypass grafting using the "Super Pulse" dynamic pulsatile
      cardiopulmonary bypass device in patients with cerebrovascular occlusive disease.
AB  - Patients with coronary disease complicated by severe carotid or intracranial
      arterial stenosis underwent coronary artery bypass graft surgery (CABG) using a
      novel method of dynamic pulsatile cardiopulmonary bypass (Super Pulse CPB). The
      Super Pulse technique can maintain the systolic pressure and systolic-diastolic
      amplitude in such a way that they mimic the physiologic circulation. Forty-five
      patients (33 males and 12 females, mean age 65.1 years) with coronary disease who
      had a greater than 75% stenosis of the carotid or intracranial arteries were
      evaluated. Evaluation was performed for the following 3 groups: 8 patients with
      conventional pulsatile CPB (Group I), 8 patients with conventional pulsatile CPB
      plus intraaortic balloon pumping (Group II), and 29 patients with Super Pulse
      CPB. Maximum, minimum, and mean perfusion pressures during CPB were 112.7, 53.6,
      and 76.9 mmHg (integrated mean), respectively, in Group III. The systolic
      diastolic amplitude was significantly better than for Group I and similar to
      baseline pressures. No patients in Group II or Group III developed perioperative
      cerebral disorders or myocardial infarction, while in Group I perioperative
      cerebral disorders developed in 3 patients, myocardial infarction occurred in 2
      patients, and 2 patients died during hospitalization. The initial performance of
      the Super Pulse CPB indicates excellent safety, and is useful for patients with
      co-morbid cerebral arterial disease.

PMID- 10899687
TI  - Thoracoscopic debridement for acute pediatric empyema: efficacy of ultrasonic
      surgical device.
AB  - Few studies have examined thoracoscopic treatment for pediatric empyema. We
      encountered three children with thoracic empyema successfully treated by
      thoracoscopic debridement. Patients were a 3-year-old girl, a 17 month-old boy
      and a 13-year-old girl who developed thoracic empyema during therapy for
      pneumonia. We performed dissection and debridement under thoracoscopy and
      resolved fibrinopurulent collections using an ultrasonic surgical device in two
      cases to search the dissection plane while minimizing injury to the lung
      parenchyma. Ultrasonic surgical device (USUTM) is very useful for performing
      effective debridement and irrigation with minimal pleural damage. Thoracoscopic
      debridement performed early in the course of therapy is recommended even for
      acute pediatric empyema and could prevent the unnecessary open surgical
      intervention or decortication.

PMID- 10899688
TI  - An experience of a case with perforation of an aneurysm in the anterior mitral
      cusp developing after aortic valve replacement.
AB  - Mitral valve aneurysm is a rare disease and in Japan, cases of perforation which
      is considered to be mainly caused by infectious endocarditis is usually only
      encountered through case reports. We experienced a case who received aortic valve
      replacement and mitral valve annuloplasty for combined valvular heart disease of
      aortic insufficiency and mitral insufficiency followed by mitral valve
      replacement for severe mitral valve regurgitation subsequent to perforation of
      the anterior mitral cusp, leading to recovery.

PMID- 10899689
TI  - Two cases of quadricuspid aortic valve: preoperative diagnosis and surgical
      treatment.
AB  - Two cases of severe aortic regurgitation were treated surgically. Both patients
      had a quadricuspid aortic valve, which was diagnosed preoperatively by
      aortography and/or transesophageal echocardiography (TEE). In the first patient,
      both aortic and mitral valve replacement were performed with an ATS prosthetic
      valve. In the second patient, only aortic valve replacement was performed. The
      postoperative course was uneventful in both cases. Quadricuspid aortic valve is
      relatively rare. We discuss the preoperative diagnosis of quadricuspid aortic
      valve, as well as reviewing the relevant literature.

PMID- 10899691
TI  - Off-pump CABG for a patient with a brain tumor.
AB  - Coronary artery bypass grafting (CABG) without cardiopulmonary bypass (off-pump
      CABG) was performed on a patient with a brain tumor. A patient with effort angina
      of the left anterior descending artery (LAD), and diagonal branch stenosis was
      referred to us for CABG. He had a mass lesion in the brain that was diagnosed as
      meningioma involving the internal carotid artery and a middle cerebral artery. To
      avoid brain complications, we performed off-pump CABG using the internal thoracic
      and radial arteries to the LAD and a diagonal branch. Off-pump CABG was an
      effective method to avoid brain complications for patients with a brain tumor
      involving cerebral vessels.

PMID- 10899690
TI  - Aortic valve replacement with concomitant annular enlargement for small aortic
      annulus of less than 19 mm.
AB  - Three female patients with aortic stenosis associated with a severely small
      annulus underwent aortic valve replacement. In intraoperative measurements, a 19
      mm obtulator could not pass through the aortic annulus in each case. We therefore
      concluded that it would be difficult to implant an appropriate-sized prosthesis
      in a routine fashion, so we performed an annular enlargement in a modified Nicks
      procedure. By using a wide teardrop-shaped patch for enlargement and slightly
      tilting insertion of a prosthesis, a 21 mm bileaflet mechanical prosthesis could
      be inserted into the enlarged annulus. Despite being a simpler method than other
      enlarging procedures, a two- or three-sizes larger prosthesis than the native
      annulus can be inserted with relative ease. Thus, the use of a 19 mm mechanical
      prosthesis may be avoidable in most adult cases.

PMID- 10899692
TI  - Bilateral radial arterial T graft and the left thoracotomy approach for second
      redo coronary artery bypass grafting.
AB  - We herein report a case of third coronary artery bypass grafting (CABG) using a
      bilateral radial artery T graft. There were patent grafts on the anterior aspect
      of the heart other than the occluded left internal thoracic artery to the left
      anterior descending (LAD) artery. A T shaped bilateral radial artery conduit was
      anastomosed from the left subclavian artery to the LAD and first diagonal branch
      through a left thoracotomy approach. Postoperative angiography demonstrated
      excellent flow of radial artery conduits. Left thoracotomy with the use of a
      bilateral radial artery T graft is a useful substitute for anterior re-sternotomy
      entry in redo CABG.

PMID- 10899693
TI  - A case report of nonresective staple exclusion of abdominal aortic aneurysm
      associated with horseshoe kidney.
AB  - A 55 year old male with a history of intermittent claudication presented with an
      abdominal mass, and was diagnosed by abdominal computed tomography (CT) with an
      abdominal aortic aneurysm accompanying horseshoe kidney. The horseshoe kidney
      configuration and governing vessels, urinary duct course, and right common iliac
      arterial stenosis were shown by methods such as angiogram, spiral CT, and
      intravenous pyelogram before operation. At the operation, the abdomen was opened
      by a median incision and, using a staple exclusion technique, the abnormal renal
      artery was reconstructed using 189 mm knitted Y shaped dacron graft replacement
      and the great saphenous vein. The isthmus was not resected. There were no post
      operative complications, nor was there any large decrease in renal function. Good
      results were obtained, and we herein report our results together with a
      discussion of the literature.

PMID- 10899694
TI  - Instantaneous end diastolic stiffness (IEDS): a simple, load independent
      measurement of left ventricular diastolic function in patients undergoing cardiac
      surgery.
AB  - The end-diastolic pressure-volume relation is a load-independent measurement of
      diastolic function. However, its clinical utility is limited because of its
      complexity. Instantaneous end-diastolic stiffness (IEDS) is a simple to perform,
      single-point, measurement of ventricular stiffness. We have validated it against
      the end-diastolic pressure-area relation (EDPAR) in patients undergoing cardiac
      surgery. EDPARs were analyzed before and after cardiopulmonary bypass in 29
      patients and compared with IEDS. Data was collected in an additional 69 patients
      in order to estimate the range of values of IEDS. End-diastolic area (EDA)
      measured by transesophageal echocardiography (TEE) was substituted for end
      diastolic volume, and pulmonary capillary wedge pressure (PWCP) was substituted
      for end-diastolic pressure. IEDS = 100 x (log10 PWCP)/EDA. Comparison of the
      methods was done by ordinary least products regression analysis. Agreement
      between EDPAR and IEDS was identified by the absence of fixed and proportional
      bias. The maximal range of corresponding values identified by 95% confidence
      intervals was within +/- 16% of the mean indicating satisfactory agreement. The
      geometric mean and 95% confidence intervals (CI) for IEDS were 8. 7 mmHg/dm2 (8.1
      to 9.4) and for IEDS indexed to body surface area were 17.2 mmHg/dm(2)/m2 (16.0
      to 18.6). IEDS is a load independent index of left ventricular stiffness.

PMID- 10899695
TI  - Development of chondroitin sulfate proteoglycans in the central auditory system
      of rats correlates with acquisition of mature properties.
AB  - Chondroitin sulfate proteoglycans (CSPGs) are macromolecules which regulate the
      structural organization of the extracellular matrix and can mediate cell
      migration and axonal growth. Here the spatiotemporal distribution of CSPGs in the
      central auditory system of rats was investigated using a polyclonal antiserum. In
      adult brains, CSPGs surrounded many neuronal cell bodies and proximal dendrites
      at all stations of the auditory pathway except the medial geniculate body. During
      development, CSPG expression became visible at postnatal day (P) 4 in the
      superior olivary complex, at P8 in the midbrain, and at P18 in the cortex.
      Immunoreactivity increased strongly until P12 in the brainstem and until P24 in
      the cortex. The adult-like pattern in the pontine nuclei, the midbrain, and the
      cortex was seen at P12, P29, and P35, respectively. The relatively late
      expression of strong immunoreactivity indicates that the CSPGs are involved in
      the maturation of axonal connections, but not in early processes such as cell
      migration or neurite outgrowth.

PMID- 10899696
TI  - D-Methionine attenuates inner hair cell loss in carboplatin-treated chinchillas.
AB  - Carboplatin, a second-generation platinum-based antineoplastic drug,
      preferentially destroys inner hair cells (IHCs) in the chinchilla while sparing
      outer hair cells (OHCs). D-Methionine (D-Met), a sulfur-containing amino acid,
      has been shown to protect hair cells from cisplatin damage in rats, but its
      ability to protect IHCs from carboplatin damage has not yet been evaluated in the
      chinchilla. We tested whether D-Met would protect the hair cells in the
      chinchilla from carboplatin. Animals were divided into two groups: a control
      group that only received carboplatin (100 mg/kg, i.p.) and an experimental group
      that received 300 mg/kg D-Met (i.p.) 30 min before carboplatin treatment.
      Ototoxicity was assessed by measuring the amount of IHC and OHC loss. Average IHC
      loss in the group treated with D-Met was 62% compared with 84% in the untreated
      control group. Thus, D-Met causes a statistically significant reduction in IHC
      loss induced by carboplatin.

PMID- 10899697
TI  - Progressive deterioration of central components of auditory brainstem responses
      during postnatal development of the myelin mutant taiep rat.
AB  - Auditory brainstem responses (ABRs) were evaluated during the postnatal
      development (P10-P180) of taiep rats, neurological mutants characterized by early
      abnormal myelin development and subsequent demyelination of the CNS. The disorder
      is produced by an autosomal recessive mutation trait that affects the
      oligodendrocytes but not the Schwann cells. After onset of ABRs (P12-P14), taiep
      rats and their nonaffected heterozygous littermates that served as controls
      showed a similar pattern of maturation for wave I. The central waves (In-IV)
      showed significantly longer latencies in the mutants. By P60-P180, the later
      waves (III and IV) were frequently difficult to discern. From the onset of ABRs,
      the interpeak latency I-IV, corresponding to the central conduction time (CCT) of
      the auditory pathway, showed in taiep rats significantly longer values than
      controls. After an initial reduction, proportional to that of control rats, the
      CCT value increased progressively during the second month of the mutants' lives.
      The electrophysiological results of the present study strongly support the
      hypothesis that mutation in the taiep rat impairs neuromaturation of the central
      auditory pathway in the brainstem by affecting the myelination process in the
      CNS.

PMID- 10899698
TI  - Electrocochleography potentials evoked by condensation and rarefaction clicks
      independently derived by a new numerical filtering approach.
AB  - The cochlear microphonic potential (CM) and the compound action potential (CAP)
      cannot be measured separately but only in combination. In the literature their
      individual estimates are conventionally recovered by the so-called CM
      cancellation technique. This method averages the potential obtained in response
      to rarefaction and condensation clicks under the assumption that changing the
      polarity of the clicks only affects the CM sign and does not alter the CAP in any
      way. However, both theory and evidence suggest that these hypotheses can be
      critical. In addition, recent contributions in the electrocochleography (ECochG)
      literature suggested that assessing the influence of stimulus polarity on the
      evoked CAP may constitute an indicator of clinical usefulness which the CM
      cancellation method cannot supply. In this work we propose a new algorithm to
      estimate the cochlear potentials evoked from positive clicks, CAP+ and CM+, and
      those evoked from negative clicks, CAP- and CM-, by processing the same kind and
      amount of data employed in the CM cancellation method. The application to real
      data taken from 3 subjects exhibiting quantitatively and qualitatively different
      ECochG responses at various levels of stimulation intensity is presented. In
      addition, simulated problems where the true CAP and CM are known are studied to
      permit a fair assessment of the proposed technique. Results suggest that the new
      algorithm is potentially able to point out small differences between CAP+ and CAP
      . This encourages its further employment on a larger scale.

PMID- 10899699
TI  - Passive transfer of experimental autoimmune labyrinthitis.
AB  - The aim of the present study was to establish an animal model of autoimmune
      labyrinthitis using heterologous inner ear antigen (IEAg) and to elucidate
      whether the experimentally induced labyrinthitis could be passively transferred.
      Cochlear and vestibular membranous labyrinthine tissues from bovine temporal
      bones were used as IEAg. Donor mice were inoculated intracutaneously at multiple
      sites with an emulsion consisting of equal parts of IEAg and complete Freund's
      adjuvant. After 10 days, mononuclear cells were collected from lymph nodes,
      spleen and blood of the donor mice and injected intravenously into naive
      recipient mice. Cellular infiltration was observed in the perilymphatic space of
      the cochlea of all donor and recipient mice. Endolymphatic hydrops was also
      observed in 63% of donor and 42% of recipient mice. These findings suggest that
      the experimentally induced labyrinthitis observed in this animal model was
      probably due to an autoimmune reaction to the IEAg and was passively transferred
      by a cell-mediated immune reaction.

PMID- 10899700
TI  - Significance of melatonin in antioxidative defense system: reactions and
      products.
AB  - Melatonin is a potent endogenous free radical scavenger, actions that are
      independent of its many receptor-mediated effects. In the last several years,
      hundreds of publications have confirmed that melatonin is a broad-spectrum
      antioxidant. Melatonin has been reported to scavenge hydrogen peroxide
      (H(2)O(2)), hydroxyl radical (HO(.)), nitric oxide (NO(.)), peroxynitrite anion
      (ONOO(-)), hypochlorous acid (HOCl), singlet oxygen ((1)O(2)), superoxide anion
      (O(2)(-).) and peroxyl radical (LOO(.)), although the validity of its ability to
      scavenge O(2)(-). and LOO(.) is debatable. Regardless of the radicals scavenged,
      melatonin prevents oxidative damage at the level of cells, tissues, organs and
      organisms. The antioxidative mechanisms of melatonin seem different from
      classical antioxidants such as vitamin C, vitamin E and glutathione. As electron
      donors, classical antioxidants undergo redox cycling; thus, they have the
      potential to promote oxidation as well as prevent it. Melatonin, as an electron
      rich molecule, may interact with free radicals via an additive reaction to form
      several stable end-products which are excreted in the urine. Melatonin does not
      undergo redox cycling and, thus, does not promote oxidation as shown under a
      variety of experimental conditions. From this point of view, melatonin can be
      considered a suicidal or terminal antioxidant which distinguishes it from the
      opportunistic antioxidants. Interestingly, the ability of melatonin to scavenge
      free radicals is not in a ratio of mole to mole. Indeed, one melatonin molecule
      scavenges two HO. Also, its secondary and tertiary metabolites, for example, N(1)
      acetyl-N(2)-formyl-5-methoxykynuramine, N-acetyl-5-methoxykynuramine and 6
      hydroxymelatonin, which are believed to be generated when melatonin interacts
      with free radicals, are also regarded as effective free radical scavengers. The
      continuous free radical scavenging potential of the original molecule (melatonin)
      and its metabolites may be defined as a scavenging cascade reaction. Melatonin
      also synergizes with vitamin C, vitamin E and glutathione in the scavenging of
      free radicals. Melatonin has been detected in vegetables, fruits and a variety of
      herbs. In some plants, especially in flowers and seeds (the reproductive organs
      which are most vulnerable to oxidative insults), melatonin concentrations are
      several orders of magnitude higher than measured in the blood of vertebrates.
      Melatonin in plants not only provides an alternative exogenous source of
      melatonin for herbivores but also suggests that melatonin may be an important
      antioxidant in plants which protects them from a hostile environment that
      includes extreme heat, cold and pollution, all of which generate free radicals.

PMID- 10899701
TI  - Pharmacology and physiology of melatonin in the reduction of oxidative stress in
      vivo.
AB  - This brief resume summarizes the evidence which shows that melatonin is a
      significant free radical scavenger and antioxidant at both physiological and
      pharmacological concentrations in vivo. Surgical removal of the pineal gland, a
      procedure which lowers endogenous melatonin levels in the blood, exaggerates
      molecular damage due to free radicals during an oxidative challenge. Likewise,
      providing supplemental melatonin during periods of massive free radical
      production greatly lowers the resulting tissue damage and dysfunction. In the
      current review, these findings are considered in terms of neurodegenerative
      diseases, cancer, ischemia/reperfusion injury and aging. Besides being a highly
      effective direct free radical scavenger and indirect antioxidant, melatonin has
      several features that make it of clinical interest. Thus, melatonin is readily
      absorbed when it is administered via any route, it crosses all
      morphophysiological barriers, e.g., blood-brain barrier and placenta, with ease,
      it seems to enter all parts of every cell where it prevents oxidative damage, it
      preserves mitochondrial function, and it has low toxicity. While blood melatonin
      levels are normally low, tissue levels of the indoleamine can be considerably
      higher and at some sites, e.g., in bone marrow cells and bile, melatonin
      concentrations exceed those in the blood by several orders of magnitude. What
      constitutes a physiological level of melatonin must be redefined in terms of the
      bodily fluid, tissue and subcellular compartment being examined.

PMID- 10899702
TI  - Biological basis and possible physiological implications of melatonin receptor
      mediated signaling in the rat epididymis.
AB  - The mammalian epididymis plays an important role in sperm maturation, an
      important process of male reproduction. Specific high-affinity 2
      [(125)I]iodomelatonin binding sites, satisfying the pharmacokinetic properties of
      specific receptors, have been found in the rat corpus epididymis, suggesting a
      direct melatonin action on epididymal physiology. Subsequent molecular and cell
      biology studies have identified these 2-[(125)I]iodomelatonin binding sites to be
      mt(1) (MEL(1A)) and MT(2) (MEL(1B)) melatonin receptor subtypes. Changes in the
      binding characteristics of these receptors in the rat corpus epididymis in
      response to castration and steroid hormones like testosterone and hydrocortisone
      indicated that these membrane melatonin receptors are biologically functional
      receptors, whose activities are differentially regulated by testosterone and
      hydrocortisone. These melatonin receptors are coupled to pertussis toxin (PTX)
      sensitive G(i) protein and probably participate in androgenic and adrenergic
      regulation of rat corpus epididymal epithelial cell functions. Furthermore, rat
      corpus epididymal epithelial cell proliferation was stimulated by melatonin,
      whose action was dependent on the concentration and duration of exposure to the
      hormone. Interestingly, an MT(2) receptor ligand (4-phenyl-2
      propionamidotetraline, 4-P-PDOT) induced a stimulatory effect on epididymal
      epithelial cell proliferation similar to that produced by melatonin. In contrast,
      a nuclear melatonin receptor agonist (1-[3-allyl-4-oxo-thiazolidine-2-ylidene]-4
      methyl-thiosemi-car bazone , CGP52608) and 8-bromo-cAMP inhibited epididymal
      epithelial cell proliferation. Taken together, our data lead us to postulate that
      one of the possible physiological functions of melatonin on the rat epididymis is
      the stimulation of mt(1) and MT(2) melatonin receptors resulting in the
      inhibition of cAMP signaling and an increase in epithelial cell proliferation.

PMID- 10899703
TI  - Photic regulation of mt(1) melatonin receptors and 2-iodomelatonin binding in the
      rat and Siberian hamster.
AB  - We have investigated the photic regulation of melatonin receptors both at the
      level of binding capacity and mt(1) mRNA expression in the suprachiasmatic
      nucleus (SCN) and the pars tuberalis (PT) of the pituitary of two species: a
      highly photoperiodic one, the Siberian hamster, and a nonphotoperiodic one, the
      Wistar rat. This study has been performed by looking at the effect of a light
      pulse applied during the night on the two receptor parameters. The results show
      that the photic regulations of mt(1) mRNA expression and receptor density are
      distinct from each other in both the SCN and PT of the two species studied. They
      also show that, depending on the species and the structure, this regulation may
      implicate either the circadian clock or melatonin.

PMID- 10899705
TI  - Melatonin and biological rhythms.
AB  - Circadian and seasonal rhythms are a fundamental feature of all living organisms.
      The functional mechanism involved is built around internal biological clock(s)
      and the hormone melatonin (Mel) is one of its critical components. Although
      numerous other sources have been identified (retina, harderian gland, gut), in
      vertebrates Mel is primarily produced by the pineal gland during the dark period
      of the light-dark cycle. This rhythmic Mel is generated directly by circadian
      clock(s). The Mel rhythm is thus an important efferent hormonal signal from the
      clock. The periodic secretion of Mel might thus be used as a circadian mediator
      of a system that can 'read' the message. The duration of the nocturnal Mel
      production is directly proportional to the length of the dark period. It is
      through these changes in duration that the brain integrates the photoperiodic
      information. In essence, the Mel rhythm appears to be an endocrine code of the
      environmental light-dark cycle conveying photic information that is used by
      organisms for both circadian and seasonal temporal organization. The major
      question arising from this effect of Mel concerns it precise mechanism of action.
      From the data reported in the present minireview, it appears that the
      photoneuroendocrine mechanism is not fundamentally different in vertebrates at
      least as far as the role of Mel is concerned.

PMID- 10899704
TI  - Nuclear receptors are involved in the enhanced IL-6 production by melatonin in
      U937 cells.
AB  - This report shows that melatonin enhances IL-6 production by U937 cells via a
      nuclear receptor-mediated mechanism. Resting U937 cells only express membrane
      (mt1) melatonin receptors. In these cells, melatonin did not modify basal
      production of IL-6 or when activated by PMA plus lipopolysaccharide, a treatment
      that downregulates the expression of mt1 receptor. However, in U937 cells
      activated with IFN-gamma, which induces the expression of the ROR alpha 1 and ROR
      alpha 2 nuclear receptors and represses the expression of the mt1 receptor,
      melatonin can activate IL-6 production. These results show that the expression of
      nuclear melatonin receptor but not membrane receptors is sufficient for melatonin
      to activate cytokine production in human lymphocytic and monocytic cell lines.

PMID- 10899706
TI  - Ganglion cells density and retinal resolution in the sea otter, Enhydra lutris.
AB  - The topographic distribution, density, and size of ganglion cells were studied in
      retinal wholemounts of the sea otter, Enhydra lutris. The cell distribution
      showed a well defined horizontal streak of higher cell density, and within this
      streak, a narrow area of the highest cell density. The peak cell density in this
      area ranged from 4050 to 4400 cells/mm(2), with a mean of 4225 cells/mm(2). The
      ganglion cell size ranged from 7 microm to 47 microm but the majority of cells
      were 7 to 30 microm. Cell size distribution revealed three size groups: 7-16, 17
      28, and 29-47 microm. The highest-density area contained mainly small (7-16
      microm) cells. The cell-density data predict a retinal resolution around 7' in
      water. Retinal organization in the sea otter exhibits more properties common with
      terrestrial rather than aquatic mammals, both in terms of ganglion cell
      characteristics and in terms of their topographic distribution.

PMID- 10899707
TI  - The ocular morphology of the southern hemisphere lamprey Mordacia mordax
      Richardson with special reference to a single class of photoreceptor and a
      retinal tapetum.
AB  - A description is given of the morphological and ultrastructural characteristics
      of the eye of Mordacia mordax, one of the two parasitic species of the southern
      hemisphere lamprey family Mordaciidae. The avascular retina is well
      differentiated, containing two ganglion cell sublaminae, two layers of horizontal
      cells and a large population of displaced bipolar cells. Intermediate filaments,
      which stain positively for glial fibrillary acidic protein (GFAP), lie in
      perpendicularly-arranged bundles between the two layers of horizontal cells. M.
      mordax contains only a single type of rod-like photoreceptor, in contrast to
      representatives in the other two lamprey families Geotriidae and Petromyzontidae,
      which possess three (two cone-like and one rod-like) and two (one cone and one
      rod) types of photoreceptor, respectively. The large photoreceptors of M. mordax
      possess a large mitochondrial ellipsosome, a cylindrical outer segment with
      incisures, and a nucleus immediately abutting the outer limiting membrane. The
      photoreceptors are arranged in an hexagonal array with their outer segments
      surrounded by a retinal tapetum which elicits a yellow fundal eyeshine. The
      tapetum contains both diffuse (vitread spheroidal granules) and specular (sclerad
      needles) reflectors. The characteristics of the eye of M. mordax are related to
      the diurnal burrowing of this species during its upstream migration, a feature
      not found in the other two extant families of lampreys. The absence of cone-like
      photoreceptors and the presence of a tapetum suggest that although photopic
      vision is probably greatly diminished, characteristics have been evolved by the
      eye to maximize light capture and increase sensitivity in the low light
      intensities encountered during this species' nocturnal migration.

PMID- 10899708
TI  - Functional connectivity among limbic brain areas: differential effects of
      incubation temperature and gonadal sex in the leopard gecko, Eublepharis
      macularius.
AB  - The neural basis of individual differences in behavior has been studied primarily
      by analyzing the properties of specific neural areas. However, because of the
      organization of the nervous system, it is also plausible that differences in
      behavior are mediated by differences in the interactivity or functional
      connectivity among brain nuclei in particular neural circuits. In the leopard
      gecko, Eublepharis macularius, the temperature of the egg during incubation not
      only determines gonadal sex, but also shapes the sociosexual behaviors,
      reproductive physiology, and hormone sensitivity of adult animals. In this study
      the effects of both incubation temperature and gonadal sex on functional
      connectivity among limbic brain areas were examined. Functional connectivity was
      assessed by analyzing covariance patterns in metabolic capacity, as revealed by
      quantitative cytochrome oxidase histochemistry. It was hypothesized that
      incubation temperature and gonadal sex affect the propensity to display
      aggressive or sexual behaviors by altering the functional connectivity within
      relevant neural circuits. The correlations of metabolic capacity between the
      anterior hypothalamus and both the septum and preoptic area were significant only
      in relatively aggressive individuals, suggesting that these circuits may regulate
      the phenotypic variation in aggressiveness caused by incubation temperature. The
      correlations between the ventromedial hypothalamus and both the dorsal
      ventricular ridge and septum were significant only in females, suggesting that
      these circuits may modulate female-typical sexual behaviors. Correlations among
      preoptic, hypothalamic and amygdalar areas tended to be distributed across both
      sexes, suggesting that there may be shared pathways underlying the expression of
      male-typical and female-typical behaviors.

PMID- 10899709
TI  - Temperature dependence of electrocommunication signals and their underlying
      neural rhythms in the weakly electric fish, Apteronotus leptorhynchus.
AB  - Weakly electric fish emit an electric communication signal that is controlled by
      a highly specialized neural circuit. In Apteronotus, the continuous electric
      organ discharge (EOD) is generated by electrotonically coupled neurons in the
      hindbrain pacemaker nucleus, and transient EOD modulations involve chemical
      synapses from descending midbrain and thalamic prepacemaker nuclei. We
      characterized the effects of temperature change (18-32 degrees C) on both the
      continuous EOD and EOD modulations, chirps, in A. leptorhynchus. EOD frequency
      was linearly related to temperature (Q(10)=1.62). By contrast, the temperature
      dependence of EOD amplitude changed with temperature. Amplitude increased steeply
      with temperature below 25 degrees C (Q(10)=2.0), but increased only gradually
      above 25 degrees C (Q(10)=1.15). EOD waveform, and consequently harmonic content,
      was also affected by temperature. The amplitude of the second harmonic was
      relatively high at both low and high temperature and relatively low at
      intermediate temperatures. The amplitude of the third harmonic increased
      monotonically with temperature. Thus, temperature has qualitative as well as
      quantitative effects on the production of the EOD. Chirp rate (Q(1)0=3.2) had a
      higher temperature dependence than that of the continuous EOD, which likely
      reflects its reliance on chemical rather than electrotonic synapses. In vitro
      pacemaker firing frequency had a similar, but slightly higher Q(10) (1.82) than
      that of the EOD frequency.

PMID- 10899710
TI  - Three-dimensional organization of microtubules in tumor cells studied by confocal
      laser scanning microscopy and computer-assisted deconvolution and image
      reconstruction.
AB  - Confocal microscopy, image deconvolution and computer-assisted methods have been
      used to reconstruct the three-dimensional (3-D) distribution of tubulin in cells.
      The techniques were applied to tumor cells growing under regular culture
      conditions (planar cultivation) and those penetrating into reconstituted collagen
      matrices (spatial cultivation). As expected the application of deconvolution
      algorithms enhanced the resolution of results. The deconvolution using the
      maximum likelihood estimation included the measurement of the point spread
      function of the optical setup. The data visualization of the resulting data sets
      uses volume as well as surface rendering approaches. The 3-D reconstruction gives
      a clear image of the spatial arrangement of tubulin fibers in relation to cell
      shape and position of other cellular organelles, particularly the nucleus. The
      tubulin forms an intricate network of fibers of variable thickness. The highest
      tubulin concentrations appear in the cell periphery and particularly in
      pseudopodia/invadopodia. This is indicative of an enhanced transport of
      intracellular material facilitating cell movement and lysis of the extracellular
      matrix. The investigation is assumed to stimulate further experiments using a
      variety of techniques leading to the complete understanding of the spatial
      architecture of living cells.

PMID- 10899711
TI  - Regeneration of mouse lip epidermis after cryo treatment. Hemidesmosome formation
      and HSPG (heparan sulfate proteoglycan) distribution in basement membrane.
AB  - The processes of degeneration and the regeneration of the lip epidermal cells was
      observed by electron microscopy, focussing on the substance and the structure of
      the lamina lucida, on which regenerating cells migrated. After the repetitive
      freezing and thawing treatment, epidermal cells degenerated and detached from the
      dermis. The separation occurred between the epidermal cells and the basement
      membrane, leaving a small amount of cell debris on the lamina densa. After the
      separation of the epidermis, there were some thick parts in the lamina densa
      which appeared to be the part below hemidesmosomes. Regenerating epidermal cells
      migrated from the nondegenerated area along the cellular surface of the old
      lamina densa. They migrated over the cell debris which was gradually
      phagocitized, and formed new hemidesmosomes with the old lamina densa.
      Regenerating epidermal cells did not make close contact with the old lamina densa
      during their migration, but there was a clear space in between, indicating that
      some of the materials and the structure of the lamina lucida of the old basement
      membrane was preserved. By immunoelectron microscopy using anti-HSPG (heparan
      sulfate proteoglycan) antibody, it became clear that after the epidermal
      separation, HSPG was preserved in the basement membrane to some extent,
      especially in the thick parts of the lamina densa located below. The
      immunoelectron micrographs support the view that hemidesmosomes may reform at the
      previous locations at the old lamina densa.

PMID- 10899712
TI  - Distribution of carbonic anhydrase isozyme VI in the developing bovine parotid
      gland.
AB  - The distribution of bovine carbonic anhydrase isozyme VI (CA-VI), purified from
      bovine saliva, was studied immunohistochemically using antiserum against bovine
      CA-VI in bovine parotid glands during fetal and postnatal development. A weak
      expression of CA-VI in undifferentiated epithelial cells and ductal cells was
      observed in a 4- to 5-month-old fetus with a 26-cm crown-rump length. The
      reaction in both acinar and ductal cells subsequently persisted during late
      gestation and birth. Although anti-CA-VI reactivity was still seen in both
      regions immediately following birth, the reactivity had almost completely
      disappeared from most duct segments by 1 month following birth. Changes in the
      localization and time-dependent expression of the isozyme in parotid glands may
      reflect changes in the biological function of structurally closely related
      isozymes.

PMID- 10899713
TI  - Immunohistochemical and ultrastructural study of pituitary folliculostellate
      cells during aging in rats.
AB  - The impact of aging on pituitary folliculostellate (FS) cells is not well known.
      The aim of the work reported here was to carry out a quantitative
      immunohistochemical assessment of the FS population in male and female rats
      during aging and to correlate the findings with possible changes at the
      ultrastructural level. Young (4 months), old (20 months) and senescent (29
      months) Sprague-Dawley rats of both sexes were sacrificed by rapid decapitation,
      their pituitaries dissected and processed by both light immunohistochemistry and
      electron microscopy. Serial sections (4 microm) were obtained at different levels
      and immunostained by means of rabbit anti-S100 serum as the primary antibody and
      a peroxidase-mediated EnVision System (Dako). Measurement of volume density (VD)
      and cell density (CD) was made in S100-reacting elements by means of an image
      analysis system (Imaging Technology, Optimas). These parameters were found to be
      significantly (p < 0.05) decreased in old and senescent rats as compared to young
      animals. In senescent females, which presented a high incidence of
      microprolactinomas, a significant (p < 0.01) increment of VD and CD was observed
      in FS cells in the area surrounding the adenomas, together with a marked decrease
      in those parameters within the tumors. Sexual dimorphism was not found except for
      the prolactinoma-bearing female group. The ultrastructure of FS cells showed the
      typical characteristics previously described in the pituitary gland. Only
      moderate changes in the endoplasmic reticulum were observed in old and senescent
      animals. We conclude that aging has a clear effect on the morphology of the
      pituitary FS cell population.

PMID- 10899714
TI  - Early bone healing events following rat molar tooth extraction.
AB  - Healing of the rat tooth extraction socket occurs rapidly, indicating a mechanism
      for cancellous bone formation occurring swiftly throughout the matrix. The
      residual periodontal ligament is evident at 2 days after extraction and its rich
      collagen type III fibre content may form a template for future cancellous bone
      formation. In the remainder of the early tooth extraction socket, fibronectin
      staining was generalized. The widespread distribution of fibronectin staining has
      given rise to speculation that the function of fibronectin may be important in
      granulation tissue formation, by providing a template matrix for fibroblast
      migration. Osteoprogenitor cells migrated into the socket from the surrounding
      bone, and produced decorin and proMMP-13 (procollagenase-3). ProMMP-13 was only
      expressed at sites of new bone formation, e.g. the border of the recently formed
      trabecular islands or the periphery of the closing socket. Collagen type I fibres
      were formed later, and were especially evident at 6 days after extraction. The
      pattern of distribution of both collagen type I and III fibres were similar as
      they passed from the bone margin towards the centre of the socket - in the same
      direction as the forming bone trabeculae. Bone formation occurs by rapid movement
      of the osteoprogenitor cells along these collagen fibres to allow a rapid
      healing, rather than that of resorption followed by slow bone deposition.

PMID- 10899715
TI  - Ultrastructural characterization of the rabbit mandibular condyle following
      experimental induction of anterior disk displacement.
AB  - Previous studies in our laboratory have shown that surgical induction of anterior
      disk displacement (ADD) in the rabbit craniomandibular joint (CMJ) leads to
      cellular and extracellular alterations consistent with osteoarthritis. Similar
      findings were also reported in human ADD as well as osteoarthritis of other
      joints. The purpose of this study was to further characterize these
      histopathological findings at the ultrastructural level. The right joint of 15
      rabbits was exposed surgically and all discal attachments were severed except for
      the posterior attachment. The disk was then repositioned anteriorly and sutured
      to the zygomatic arch. The left joint served as a sham-operated control. Ten
      additional joints were used as nonoperated controls. Mandibular condyles were
      excised 2 weeks following surgery and processed for transmission electron
      microscopy. Experimental condyles showed neovascularization, fibrillation and
      vacuolation of the extracellular matrix and an increase in the number of
      apoptotic cells compared to controls. In addition, chondrocytes in osteoarthritic
      cartilage showed an increase in the amounts of rough endoplasmic reticulum and
      Golgi complex suggesting an increase in protein synthesis. The presence of thick
      collagen fibers in osteoarthritic cartilage supports our previous
      immunohistochemical results of the presence of type I collagen instead of
      normally existing type II collagen. It was concluded that surgical induction of
      ADD in the rabbit CMJ leads to ultrastructural changes in the mandibular condylar
      cartilage consistent with degenerative alterations known to occur in
      osteoarthritis.

PMID- 10899716
TI  - Unilateral masticatory function changes the proteoglycan content of mandibular
      condylar cartilage in rabbit.
AB  - Unilateral masticatory function was induced in 10-day-old rabbits by grinding the
      right side molars out of occlusion under general anesthesia. The grinding
      procedure was repeated twice a week thereafter. They were killed at the ages of
      25 and 35 days. Rabbits of the same age with uninterfered occlusions served as
      controls. The changes in articular cartilage of the mandibular condyle were
      studied biochemically and histochemically. There was a significant decrease in
      the proteoglycan content of the condylar cartilage in both groups of animals
      subjected to molar grinding compared to the animals with untouched occlusions.
      Especially the amount of aggregating proteoglycans was reduced. The condylar
      cartilage matrix synthesis is sensitive to loading produced by masticatory
      function during growth. The mechanical properties of the articular cartilage
      after a period of unilateral mastication will be impaired and it is possible that
      this makes the joint cartilage more susceptible to pathological events.

PMID- 10899717
TI  - Growth pattern of the maxillary sinus in the miniature pig (Sus scrofa).
AB  - The biological role of the paranasal sinuses is obscure, can be elucidated
      through a cross-sectional growth study of the maxillary sinus in miniature pigs.
      The maxillary sinus area was obtained from lateral cephalograms of left skull
      halves of 103 female miniature pigs of known ages, from newborn to 24 months. Out
      of several nonlinear models, the growth of the maxillary sinus was best described
      with the Gompertz model. The first derivative of the Gompertz curve revealed an
      increase in the growth rates of the maxillary sinus until 4 months, after which
      sinus growth slowed down. The eruption of the permanent molars did not seem to
      have a significant influence on this growth pattern. Furthermore, growth in
      maxillary sinus size in the miniature pig does not follow growth in skull size
      closely, which showed the highest growth rates in newborn animals. In addition, a
      correlation analysis revealed that the relationship between maxillary sinus area
      and different characteristics of the masticatory apparatus (including linear
      cranial dimensions, and the dry weight of the masseter and zygomatico
      mandibularis muscles) were influenced greatly by skull size. These results
      suggest that the existence of pneumatic cavities within the mammalian skull is
      not satisfactorily explained solely by an architectural theory. Epigenetic
      factors are likely to influence the final shape of the maxillary sinus.

PMID- 10899718
TI  - Geometrical analysis of the femoral neck torsion.
AB  - By the geometrical analysis of three cross sections the surface along the femoral
      neck, the second moments of area and the major axes of symmetry are obtained. The
      surface passing through these axes determined in each section, from the lateral
      to the medial third of the neck, is one of the two anatomical surfaces of
      symmetry of the neck. The geometric structure defined by this surface is a
      helicoid. No plane, in the ordinary sense of the word, has to be defined in the
      femoral neck. At the trochanteric junction, the major axis is inclined about 17
      degrees on the anteversion plane, twists anteriorly and becomes more horizontal
      to finish with a mean inclination of 60 degrees at the cephalic junction.
      Surprisingly, this twist and then the neck torsion are in opposite directions to
      that suggested by the bony markers, often taken as a reference and reported in
      the anatomical descriptions.

PMID- 10899720
TI  - Lymphocyte subsets and cellular immunity in patients with chronic pancreatitis.
AB  - BACKGROUND: An abnormal immune response may play a pathogenetic role in chronic
      pancreatitis. However, to date characterization of the systemic immunological
      changes in patients with chronic pancreatitis has not been undertaken. METHODS:
      Lymphocyte phenotypes and proliferation ((3)H-thymidine) after stimulation with
      mitogens and interleukin-2 were studied in peripheral mononuclear cells from 11
      patients with chronic pancreatitis (alcohol-induced n = 6; idiopathic
      pancreatitis n = 5). The natural killer cell activity was investigated in a
      (51)Cr release cytotoxicity assay. In vitro cytokine release of stimulated
      mononuclear cells was measured. RESULTS: Flow cytometric studies showed a
      significant decrease in the percentage of circulating CD8+, CD56+ and CD25+ cells
      in patients with chronic pancreatitis independent of the etiology. Comparing all
      patients with chronic pancreatitis to controls, the proliferation rate was not
      significantly increased, but patients with pain (n = 5) showed increased
      proliferation in comparison to patients without pain (n = 6). No significant
      difference in natural killer cytotoxicity was observed. The in vitro release of
      tumor necrosis factor-alpha and interleukin-10 by stimulated mononuclear cells
      was increased. CONCLUSIONS: Chronic pancreatitis is accompanied by systemic
      immune dysregulation. The observed changes in peripheral mononuclear cells reveal
      additional evidence that the cell-mediated immune response may contribute to the
      development of pain and tissue destruction in chronic pancreatitis.

PMID- 10899719
TI  - Protective action of lipopolysaccharidesin rat caerulein-induced pancreatitis:
      role of nitric oxide.
AB  - Lipopolysaccharides (LPS), the component of the cell wall of gram-negative
      bacteria, have been implicated in the pathogenesis of acute pancreatitis, but the
      mechanism of their action on the pancreas has not been fully explored. The aim of
      this study was to investigate the effects of various doses of LPS on the
      integrity of intact pancreas and that involved in acute caerulein-induced
      pancreatitis (CIP) in the rat and to compare these effects with those of nitric
      oxide (NO) donor, S-nitrose-acetylpenicillamine (SNAP). The expression of
      constitutive NO synthase (cNOS) and inducible NO synthase (iNOS) mRNA was also
      examined in the isolated pancreatic acini obtained from the inflamed pancreas of
      rats treated with LPS. CIP was produced by subcutaneous (s.c.) infusion of
      caerulein (5 microg/kg.h for 5 h) to conscious rats. Bolus injections of various
      doses of LPS (0.1, 1, 10, 20 or 40 mg/kg) or SNAP (1.5, 3 or 6 mg/kg) were made
      intraperitoneally (i.p.) either alone or 30 min prior to s.c. infusion of
      caerulein to induce CIP. Infusion of caerulein produced acute pancreatitis
      confirmed by histological examination and manifested by an increase of pancreatic
      mass (by about 200%). Blood levels of amylase and lipase were augmented by 400
      and 800% respectively, whereas the pancreatic blood flow (PBF) was decreased by
      50% in rats with CIP. Injection of low doses of LPS (0.1-1 mg/kg i.p.) or SNAP
      (1.5-3 mg/kg i.p.) 30 min prior to caerulein infusion reversed the harmful
      effects of pancreatic overstimulation with caerulein and reduced significantly
      the histological manifestations of CIP such as edema, neutrophil infiltration and
      vacuolization of the acinar cells. These protective effects of low doses of LPS
      pretreatment on the pancreas were completely antagonized by the suppression of
      the activity of NO synthase (NOS) with N(G)-nitro-L-arginine (L-NNA) applied (20
      mg/kg i.p.) 15 min prior to the LPS injection. Combination of L-arginine (100
      mg/kg i.p.), a substrate for NOS, with L-NNA given prior to low doses of LPS,
      restored the LPS-induced protection of the pancreas in rats with CIP. In
      contrast, higher doses of LPS (20-40 mg/kg i.p.) or SNAP (6 mg/kg i.p.), which
      produced a significant fall of the PBF, did not protect the pancreas against CIP.
      Administration of various doses of LPS to rats with CIP resulted in significant
      and dose-dependent stimulation of NO biosynthesis in the isolated acini obtained
      from the pancreas of these animals. LPS enhanced the expression of both cNOS and
      iNOS in the pancreatic acini obtained from rats subjected to CIP. The signal for
      cNOS mRNA was detected in all samples, reaching peak at the protective dose of
      LPS (1 mg/kg i. p.), while iNOS was overexpressed only at the highest doses of
      LPS that failed to exhibit the protective activity. We conclude that the
      pretreatment with low doses of LPS protects the pancreas against the damage
      provoked by CIP and this effect could be attributed, at least in part, to the
      activation of L-arginine-NO system in the pancreas.

PMID- 10899721
TI  - End expiration is more accurate than mid respiration in measuring lower
      esophageal sphincter pressure.
AB  - BACKGROUND/AIMS: Two ways popularly used to measure lower esophageal sphincter
      pressure are the mid-respiratory and end-expiratory methods. The aim of this
      study was to compare the suitability of these methods in the manometric
      assessment of patients with endoscopically documented esophagitis. METHODS:
      Manometry was performed on 22 consecutive patients to determine whether medical
      therapy or surgery was the more appropriate treatment strategy. Lower esophageal
      sphincter pressure was measured during a slow station pull-through. End
      expiratory lower esophageal sphincter pressure was assessed by measuring the
      highest trough which coincided with end expiration. Mid-respiratory lower
      esophageal sphincter pressure was assessed by bracketing the highest pressure
      over >/=3 respiratory cycles and measuring the mid point. RESULTS: Mid
      respiratory lower esophageal sphincter pressure (25.6 mm Hg) was higher (p <
      0.0001) than end-expiratory lower esophageal sphincter pressure (15.7 mm Hg).
      Nine (41%) end-expiratory lower esophageal sphincter pressures were abnormally
      low (i.e., <10 mm Hg), whereas three (14%) mid-respiratory lower esophageal
      sphincter pressures were abnormally low (i.e., <14 mm Hg; p = 0.042). CONCLUSIONS
      Mid-respiratory lower esophageal sphincter pressure measurement includes
      respiratory artifact and does not accurately measure lower esophageal sphincter
      pressure. End-expiratory sphincter pressure better identifies potential surgical
      candidates.

PMID- 10899722
TI  - Evidence of abnormal esophageal motility in syndrome X by radionuclide esophageal
      transit test.
AB  - In 30 patients with syndrome X, esophageal motility was evaluated by radionuclide
      esophageal transit test (RETT). Esophageal motility measurements included
      esophageal mean transit time (MTT), residual fraction (RF), and retrograde index
      (RI). In comparison with 25 age- and sex-matched healthy volunteers, 66% of the
      patients with syndrome X had abnormal RETT findings including 50% of cases with
      longer MTT, 50% of cases with higher RF, and 33% of cases with higher RI. In
      addition, the mean values of MTT, RF, and RI in patients with syndrome X were
      significantly higher than those of healthy volunteers. We conclude that abnormal
      esophageal motility occurred in a large portion of syndrome X patients based on
      an simple and noninvasive RETT.

PMID- 10899723
TI  - Dose-related stimulatory effect of clarithromycin on interdigestive
      gastroduodenal motility.
AB  - BACKGROUND/AIMS: The effect on interdigestive gastroduodenal motility of
      different doses of clarithromycin, an antibiotic commonly used for Helicobacter
      pylori eradication, has been investigated. METHODS: Gastroduodenal motility was
      recorded by means of a low-compliance manometric system in 15 healthy subjects.
      Thirty minutes after the first phase III of the migrating motor complex,
      clarithromycin (CLA) was infused intravenously at a dose of 100 mg in 5, 250 mg
      in 5 and 400 mg in 5 subjects, randomly and in a double-blind manner, continuing
      the recording for at least 1 h. A further study was carried out on 10 subjects, 5
      of whom received 50 mg CLA and 5 normal saline with the same modalities. RESULTS:
      After 100 mg CLA a premature gastroduodenal phase III ensued in all cases, which
      showed a duration, propagation velocity and wave frequency not significantly
      different from the spontaneous one and was followed by a clear phase I. A
      premature gastroduodenal phase-III-like activity occurred in 3 cases of 250 mg
      CLA and 2 cases after 400 mg CLA, followed by a very short or absent phase I and
      characterized by a long duration of the antral phase III, while in the remaining
      cases a long-lasting sequence of about 1/min of antral waves propagated to the
      duodenum appeared, sometimes preceded by an antral phase-III-like activity not
      propagated to the duodenum. After 50 mg CLA a premature phase III appeared in 2
      cases, while a not premature phase III appeared in 2 cases after saline.
      CONCLUSION: CLA shows a dose-related stimulatory effect on interdigestive
      gastroduodenal motility varying from the initiation of a typical phase III to a
      prolonged sequence of gastroduodenal coordinated waves. These motor effects of
      CLA suggest potential therapeutic applications.

PMID- 10899724
TI  - Liver transplantation in primary biliary cirrhosis: risk assessment and 11-year
      follow-up.
AB  - BACKGROUND/AIMS: Liver transplantation (LTx) is the only established treatment in
      patients with end-stage primary biliary cirrhosis (PBC). Although short-term
      survival after LTx in this group of patients is usually good, few data exist on
      the long-term survival. The optimal timing of transplantation is difficult. Thus,
      the aims of this study were to assess the long-term survival of patients with PBC
      after LTx and to identify potential predictive factors for a positive outcome.
      METHODS: Survival of 28 patients with PBC who underwent LTx between 1985 and July
      1999 in a single center was studied by Kaplan-Meier analysis and was compared to
      predicted survival without LTx using established prognostic models for PBC, the
      Mayo and European risk scores. Potential prognostic parameters obtained before
      LTx were tested for correlation to survival. Rates of bone fractures as markers
      of hepatic osteodystrophy were compared before and after LTx. RESULTS: Median
      follow-up after LTx was 90 months with a maximum of 140 months. Actuarial
      survival of patients with PBC was 89% after 1, 5, and 10 years and was
      significantly better than estimated survival without LTx after 1-7 years as
      calculated by the Mayo and European risk scores. Of several parameters tested,
      only serum bilirubin and the prognostic scores, but no other liver function tests
      obtained immediately prior to transplantation were significantly correlated with
      survival after LTx. The duration of intensive care after LTx was not associated
      with any parameters obtained before LTx. Bone fractures were diagnosed in 43% of
      patients of whom the vast majority were osteopenic before LTx as determined by
      osteodensitometry. CONCLUSION: Long-term survival of a well-defined group of
      patients with PBC was excellent after LTx and was inversely correlated with
      preoperative serum bilirubin levels as well as Mayo and European risk scores.

PMID- 10899725
TI  - Elevated soluble tumour necrosis factor receptor serum concentrations and short
      term mortality in liver cirrhosis without acute infections.
AB  - BACKGROUND: Serum concentrations of the soluble 75-kDa tumour necrosis factor
      receptor (sTNF-R 75) are elevated in patients with severe liver disease and may
      be linked to mortality as well as to prognostic markers related to clinical
      outcome and metabolic functions in patients with liver cirrhosis. PATIENTS AND
      METHODS: We prospectively studied the relation of sTNF-R 75 to Child-Pugh score
      points and serum markers of bile acid (total serum bile acids and 7alpha
      hydroxycholesterol), lignocaine (lignocaine metabolite (MEGX) liver function test
      results) and albumin metabolism (albumin and prealbumin) in 10 healthy
      individuals and 30 patients with cirrhosis, all free of acute infections. In
      patients with cirrhosis mortality was recorded for 15 months. RESULTS: Soluble
      TNF-R 75 concentrations correlated with Child-Pugh score points (r = 0.440, p =
      0.015), MEGX test results (r(S) = -0.604, p < 0.001) and prealbumin (r(S) = -0.
      527, p < 0.001) in cirrhosis. Nonsurviving patients had almost threefold higher
      median sTNF-R 75 concentrations (29 ng/ml) than survivors (11 ng/ml) (p = 0.003).
      Soluble TNF-R 75 serum concentrations with an optimal cut off > 14 ng/ml were
      significantly more accurate in predicting patient mortality than Child-Pugh score
      points in a receiver-operator characteristic curve analysis. CONCLUSION: Soluble
      TNF-R 75 serum concentrations appear to be a promising new risk factor for
      mortality in patients with cirrhosis without acute infections.

PMID- 10899726
TI  - Severity of HCV-induced liver damage alters glucose homeostasis in noncirrhotic
      patients with chronic HCV infection.
AB  - BACKGROUND/AIMS: To investigate the link between hepatitis C infection and
      glucose intolerance, we measured insulin sensitivity, glucose effectiveness and
      beta-cell secretion in noncirrhotic HCV-infected patients with normal glucose
      tolerance according to WHO criteria as assessed by oral glucose tolerance tests.
      METHODS: Glucose, insulin and C-peptide data from frequently sampled intravenous
      glucose tolerance tests were analyzed using the minimal modeling technique for
      glucose and C-peptide to determine insulin sensitivity, glucose effectiveness,
      first and second phase insulin secretion in noncirrhotic HCV-infected patients (n
      = 10) and in healthy control subjects (n = 10). Histological activity index (HAI)
      as well as the extent of fibrosis were evaluated by scoring liver biopsies.
      RESULTS: Insulin sensitivity (2.72 +/- 1.63 vs. 6.84 +/- 1. 20 10(-4) min(-1) per
      microU/ml, p < 0.01) and glucose effectiveness (2.29 +/- 0.45 vs. 2.89 +/- 0.39
      10(-2) min(-1), p < 0.05) ere significantly lower in patients with HCV-induced
      liver disease. Insulin sensitivity was negatively related to serum alanine
      aminotransferase (r = -0.47, p < 0.05) and aspartate aminotransferase
      concentrations (r = -0.65, p < 0.05). Multiple linear regression analysis
      revealed a strong relation of insulin sensitivity with fibrosis score and HAI (r
      = -0.82, p < 0.02 for both). Second phase insulin secretion was significantly
      enhanced in HCV-infected patients (14.30 +/- 2.04 vs. 8.29 +/- 1.65 min(-1), p <
      0.05). CONCLUSIONS: HCV-infected patients with normal glucose tolerance are
      insulin and glucose resistant. The impairment of glucose tolerance appears to be
      closely related with the severity of HCV-induced liver damage.

PMID- 10899727
TI  - Refractory sprue syndrome with clonal intraepithelial lymphocytes evolving into
      overt enteropathy-type intestinal T-cell lymphoma.
AB  - INTRODUCTION: Recently, patients with refractory sprue have been shown to contain
      a clonal proliferation of phenotypically abnormal intraepithelial lymphocytes in
      their intestine. Whether this signifies early enteropathy-type intestinal T-cell
      lymphoma (EITCL) or a reactive condition is not clear. We report on a patient
      presenting with the findings of refractory sprue who subsequently developed overt
      EITCL. MATERIAL AND METHODS: Duodenal biopsies from 1997 (refractory sprue) and
      duodenal and jejunal biopsies from 1998 (intestinal T-cell lymphoma) were
      compared by immunohistochemistry and PCR for the detection of T-cell receptor
      (TCR)-gamma gene rearrangements. Clonal PCR products were sequenced. RESULTS: The
      duodenal biopsies from both 1997 and 1998 and the jejunal tumor biopsy showed
      villus atrophy and an increase of intraepithelial lymphocytes with an abnormal
      immunophenotype (CD3+, CD4-, CD8- and TCR-beta-). In all duodenal specimens
      including the one from 1997, and the jenunal tumor biopsy, an identical clonal
      amplificate was detected by enzymatic amplification of the TCR-gamma gene.
      CONCLUSION: These data suggest that refractory sprue containing a clonal
      proliferation of phenotypically abnormal intraepithelial lymphocytes may
      represent an early manifestation of EITCL. The detection of immunohistochemical
      negativity for several antigens normally found on intraepithelial lymphocytes
      such as CD8 or the TCR-beta chain in combination with clonal T-cell populations
      by PCR may be helpful in identifying refractory sprue with a malignant
      transformation.

PMID- 10899728
TI  - Nongastrointestinal disorders in the irritable bowel syndrome.
AB  - A large proportion of irritable bowel syndrome (IBS) patients also complain of
      other functional disorders, such as headache, noncardiac chest pain, low back
      pain, and dysuria. Some of these features, particularly headache, may have a
      negative influence on the outcome of IBS. In a large proportion of female IBS
      patients, sexual intercourse triggers the symptoms, and frequently IBS symptoms
      exacerbate during menses. These gynecological-type symptoms often mislead the
      patients to the gynecological clinic, which may imply unnecessary investigations
      and inappropriate treatments. The diagnostic criteria of the fibromyalgia
      syndrome include IBS, and hence, the apparent relationship of both syndromes is
      difficult to analyze. On the other hand, no convincing evidence has been produced
      to date to sustain an association between IBS and the chronic fatigue syndrome.

PMID- 10899729
TI  - A French translation of the obsessive-compulsive drinking scale for craving in
      alcohol-dependent patients: a validation study in Belgium, France, and
      Switzerland.
AB  - The Obsessive-Compulsive Drinking Scale (OCDS) is an instrument developed to
      measure cognitive aspects of alcohol craving. The aim of this study was to
      validate the French translation of the OCDS according to the international
      methodology as published by Hunt and coworkers (see text), including forward
      backward translations, patient interviews (9 patients), patient's perception of
      acceptability (15 patients), and final validation within a treatment program (50
      patients). All 74 patients were native French-speaking alcohol-dependent patients
      from Belgium, France, and Switzerland. The derived aggregated total (TOT) score
      and both subscores corresponding to the obsessive (OB) and compulsive (CP)
      dimensions were shown to be asymptomatically normal. Good internal consistencies
      were found, with Cronbach alpha: TOT = 0.88; OB = 0. 82; CP = 0.79. The test
      retest procedure was used to examine intrarater reliability (r = 0.81). The
      construct validity was examined with linear correlation of the two main
      components: r(OB, CP) = 0.62; r(OB, TOT) = 0.86; r(CP, TOT) = 0.92. Principal
      components analysis revealed two main factors: the first factor representing the
      total scale score, while the obsessive and compulsive subscale scores were
      distributed along factor two. The translated scale seems to be psychometrically
      as valid as the original English scale and confirms the psychometric properties
      of the OCDS.

PMID- 10899730
TI  - Platelet monoamine oxidase activity in alcoholics with and without a family
      history of alcoholism.
AB  - A number of studies point at platelet monoamine oxidase (MAO) activity being
      reduced in alcoholics with a family history of drinking, this being a possible
      vulnerability marker for alcoholism. To test this hypothesis, we examined a group
      of recently detoxified alcoholics with high (n = 25) and low genetic loading for
      alcoholism (n = 28) and a group of healthy controls (n = 21). Clinical
      assessments were made using the SCID II interview for psychiatric disorders, the
      Family History Assessment Module and the Semi-Structural Assessment of Genetics
      in Alcoholism, a questionnaire especially designed for genetic studies. Platelet
      MAO activity with and without ethanol stimulation and the percentage of MAO
      activity with ethanol did not differ between groups. The only significant
      difference was a lower inhibition of MAO activity with ethanol in alcoholics both
      with and without a family history compared to controls. In patients with
      antisocial personality traits, platelet MAO activity was also not found to be
      different from other alcoholics. Our findings question the hypothesis of reduced
      platelet MAO activity to be a possible vulnerability marker for alcoholism.

PMID- 10899731
TI  - Craving shift in chronic alcoholics.
AB  - In order to investigate changes in the consumption of substances that stimulate
      the reward system, 222 recently detoxified alcoholics were asked about their
      consumptional habits before as compared to after detoxification (mixed
      prospective and retrospective design). Seventy-eight point two percent reported
      an increase in consumption of coffee, cigarettes, chocolate and other sweets,
      while 34.9% managed to reduce at least one of these substances. The increase was
      significant for coffee, chocolate and other sweets. The desire for consumption of
      these substances was correlated with the maximum ever experienced desire for
      alcohol (0.232 for coffee, 0.213 for cigarettes, 0.193 for chocolate and 0.176
      for other sweets), and the actual consumption of coffee, cigarettes and sweets
      was correlated with the actual desire for alcohol (0.172, 0.157 and 0.245,
      respectively). The results lend some support to the hypothesis that psychotropic
      substances might serve as a kind of self-regulation against craving in this
      group. A possible link to biochemical theories is discussed.

PMID- 10899732
TI  - Economic evaluation of Campral (Acamprosate) compared to placebo in maintaining
      abstinence in alcohol-dependent patients.
AB  - We compared the costs of acamprosate in maintaining abstinence in weaned
      alcoholic patients, to no pharmaceutical treatment over a 24-month period. A
      controlled trial (n=448) involving a 12-month treatment with acamprosate and a 12
      month follow-up showed a significant advantage of acamprosate over placebo in the
      prevention of relapse. For the economic analysis, the average costs of relapses
      from the health insurance perspective were calculated based on a Belgian survey
      among general practitioners and on an observational prospective Belgian trial
      among specialists. Calculations resulted in net cost savings of 21,301 BEF (528
      Euro) per patient over a 24-month period for acamprosate compared to no
      pharmaceutical treatment, explained by fewer acute hospitalisations for
      detoxification and less institutionalised rehabilitation. A global anticipated
      net saving of 70 million BEF (1.74 million Euro) over 2 years was estimated for
      the Belgian health insurance.

PMID- 10899733
TI  - Inequity in the hospital care of patients with alcoholism and medication
      addiction.
AB  - In a psychiatric/ecological study, the authors investigated which aspects of a
      town district would provide an explanation to the fact that alcoholics are
      treated above average in addiction-psychiatric wards in a given city district,
      while in other districts treatment is carried out in internal medical wards. The
      research was based on data collected between 1988 and 1994 from approximately 77%
      of all patients suffering from alcohol and legal drug abuse (n = 15,473) in 41
      hospitals in Hamburg. It was established that in somatic departments, mainly
      internal medicine, 70% of male and 67% of female patients were admitted for
      alcohol and legal drug abuse. The results of a geographical analysis of
      hospitalization risks showed that the addiction-psychiatric facilities of
      psychiatric wards are mainly utilized by inhabitants from nearby districts. Risks
      of above-average hospitalization for alcoholics and legal drug abusers in
      internal wards, as well as insufficient addiction-psychiatric care, are to be
      expected in town districts where a shortage of psychiatrists exists, and where
      the unemployment rate is high. In these crucial areas, addiction-specific
      facilities, such as qualified programs for detoxication or techniques for short
      intervention, should be established within the framework of an addiction-specific
      liaison service in general hospitals.

PMID- 10899734
TI  - Stage of change of cigarette smoking in alcohol-dependent patients.
AB  - Despite the heavy burden of tobacco-related problems in alcohol-dependent
      patients, little effort has been directed toward reducing the prevalence of
      smoking in these patients. It seems reasonable to develop nicotine addiction
      treatments for alcohol-dependent patients based on the smoker's stage of change.
      To assess the stage of change for tobacco consumption and possible quitting
      barriers in alcohol-dependent patients, 88 consecutively admitted inpatients of a
      Swiss university-affiliated alcohol withdrawal clinic were interviewed with a
      semistructured schedule. More than half of the alcohol-dependent smokers (50.7%)
      considered the possibility of smoking cessation or had already decided to stop,
      although the majority (83.1%) were highly dependent smokers. Positive reinforcers
      were factors influencing motivation both to stop smoking as well as to continue
      smoking, whereas negative reinforcers had no influence. As recovering alcoholic
      patients are often interested in smoking cessation and the introduction of
      nicotine treatment interventions has been shown not to jeopardize the outcome of
      alcohol treatment, alcohol treatment programs should include counseling for
      smoking cessation. Education and training for staff is essential, as their
      beliefs and habits remain an important barrier.

PMID- 10899735
TI  - Alcohol use disorders in French university hospital patients.
AB  - The adult patients of the somatic departments of Amiens University Hospital were
      screened on a randomly selected day by interviewers who examined them using a
      structured questionnaire regarding lifestyle, with the CAGE questionnaire, and
      their daily alcohol consumption. The medical histories of all patients were
      collected. A patient was considered having an alcohol problem if one or more of
      the following criteria was fulfilled: (1) a CAGE questionnaire score of 2 or more
      positive answers; (2) an alcohol-related diagnosis. In total, 869 patients
      fulfilled the entry criteria (377 patients were excluded owing to predefined
      exclusion criteria). A hundred and sixty-seven patients (19.2%) fulfilled 1 or 2
      of the criteria for an alcohol problem. Eighty-eight patients (10.1%) had an
      alcohol-related discharge diagnosis. The prevalence of patients with a positive
      CAGE score was 13.5% and was significantly higher among male patients (22.7%)
      than among female patients (5.5%). The frequency of a higher socioeconomic status
      or the status of 'living alone' increased significantly with alcohol consumption.

PMID- 10899736
TI  - Measuring met and unmet need of drug misusers: integration of quantitative and
      qualitative data.
AB  - This paper reports on the combination of qualitative and quantitative methods
      which were used to record the attitudes to, and perceptions of, drug treatment
      services by current, ex-, and potential clients in south-east London. Three
      research instruments were employed: a structured current client satisfaction
      survey (n = 333); a questionnaire which included open-ended questions,
      administered to drug users not currently in treatment (n = 88), and focus groups
      for young drug users not in treatment (n = 14), women in treatment (n = 7) and
      men in treatment (n = 11). The data thus collected were used to construct a
      picture of local met and unmet need and obstacles to the uptake of health care,
      which is supported by more than one perspective, and which can reasonably be used
      as the basis for the planning of local health care purchase. Three major concerns
      were revealed by the data: the inadequacy of existing GP drug services; the
      deterrent effect of long waiting lists for methadone treatment, and the role of
      treatment services in relation to those drug users who acknowledge that their
      drug use is problematic, but believe that treatment services have nothing to
      offer them.

PMID- 10899737
TI  - Cells and cytokines in the pathogenesis of inflammatory bowel disease: new
      insights from mouse T cell transfer models.
AB  - Recently, a number of experimental models of human inflammatory bowel disease
      (IBD) of immunological basis have been developed. These have proven useful tools
      in the study of IBD, allowing a more detailed dissection of the pathogenesis of
      the disease. Studies from these models have revealed new, important knowledge
      about environmental factors, cell subset, cytokines and effector molecules in the
      pathogenesis of IBD. This review focuses on recent advances in the understanding
      of the development of IBD obtained from adoptive CD4+ T cell transfer models of
      the disease.

PMID- 10899738
TI  - Polymorphism of transmembrane region of MICA gene and Kawasaki disease.
AB  - Kawasaki disease is a febrile disease of children complicated with vasculitis of
      the coronary arteries and potential aneurysm formation. It has been recognized
      worldwide and appears to be increasing in frequency. Studies have found that
      Kawasaki disease is associated with major histocompatibility complex (MHC) class
      I B antigens. The MHC-class-I-chain-related gene A (MICA) is located near HLA-B.
      It has a triplet repeat microsatellite polymorphism in the transmembrane region.
      We investigated the microsatellite polymorphism in children with Kawasaki disease
      and controls. Seventy children (46 boys), age at diagnosis 1.68 +/- 1.69 years,
      with Kawasaki who were treated with aspirin as well as intravenous gamma-globulin
      were enrolled. Control subjects consisted of 154 children (87 boys), age 2.81 +/-
      2.12 years. Phenotype frequency of allele A4 in patients with aneurysm formation
      was significantly lower than in patients without aneurysms [relative risk (RR) =
      0.06, 95% confidence interval (CI) = 0.01-0.48, p = 0.00469, pc = 0.0232] and
      showed a similar tendency when compared with controls. Gene frequency of allele
      A4 was also significantly lower in patients who developed aneurysms than in
      patients who did not (RR = 0.07, 95% CI = 0.01-0.57, p = 0.0057, pc = 0.0282).
      Gene frequency of allele A5 showed a tendency to be higher in patients who
      developed aneurysms than in controls (RR = 2.35, 95% CI = 0.98-5.63, p = 0.0486,
      pc = 0. 220). Allele A5.1 tended to be negatively associated with Kawasaki
      disease (RR = 0.57, 95% CI = 0.35-0.93, p = 0.022, pc = 0.105). Our study showed
      that allele A4 was negatively associated with coronary aneurysm formation in
      Kawasaki disease. This suggests that allele A4 protects the children with
      Kawasaki disease from developing coronary aneurysms after aspirin and gamma
      globulin therapy.

PMID- 10899739
TI  - A simple estimate of the general population frequency of the MHC susceptibility
      gene for autoimmune polygenic disease.
AB  - We wished to determine the frequencies of the MHC and non-MHC susceptibility
      genes for polygenic autoimmune diseases like type 1 diabetes (IDDM). We used
      Mendelian inheritance and the Hardy-Weinberg equilibrium to calculate the
      frequencies of mating pairs and susceptible offspring under classical recessive
      and dominant inheritance of the MHC susceptibility gene. We then analyzed the
      distribution of haplotype sharing by affected sib pairs of the 4 MHC haplotypes
      in each of the kinds of mating pairs in terms of the frequency of the disease
      susceptibility gene. For IDDM, the analysis was consistent with a recessive, but
      not a dominant, MHC susceptibility gene of frequency 0.525 at a distribution of
      55, 38 and 7% of affected sib pairs who share 2, 1 and 0 MHC haplotypes,
      respectively. A simple relationship was obtained: if inheritance is recessive,
      the MHC susceptibility gene frequency is the square root of the fraction of
      affected sib pairs who share no MHC haplotypes multiplied by 4. For recessive
      inheritance, affected sib pairs who share no haplotypes are solely in families
      where both parents are homozygous MHC-susceptible. Although homozygous MHC
      susceptibles represent over 25% of the population, only 2-3% of them are IDDM
      susceptible at non-MHC susceptibility loci, also required for disease expression.
      Predictions from our analysis fit all published observations of the familial
      occurrence of disease. The analysis is general, simple and provides a single
      estimate (not a range) of the MHC susceptibility gene frequency. This approach
      should be applicable to other MHC-determined polygenic diseases.

PMID- 10899740
TI  - The Teleostei immunoglobulin heavy IGH genes.
AB  - 'Teleostei Immunoglobulin Heavy IGH Genes', the eleventh report of the 'IMGT
      Locus in Focus' section, comprises four tables: (1) 'Teleostei IGHV genes'; (2)
      'Teleostei germline IGHJ genes'; (3) 'Teleostei IGHC genes and alleles'; (4) 'FR
      IMGT and CDR-IMGT length of the Teleostei IGHV genes'. These tables are available
      at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database
      (http://imgt.cines.fr: 8104) created in 1989 by Marie-Paule Lefranc, Universite
      Montpellier II, CNRS, France.

PMID- 10899741
TI  - The telostei immunoglobulin light IGL1 and IGL2 V, J and C genes.
AB  - 'Teleostei Immunoglobulin Light IGL1 and IGL2 V, J and C Genes', the 12th report
      of the 'IMGT Locus in Focus' section, comprises 8 tables: (1) 'Teleostei IGL1V
      genes'; (2) 'Teleostei germline IGL1J genes'; (3) 'Teleostei IGL1C genes and
      alleles'; (4) 'Teleostei IGL2V genes'; (5) 'Teleostei germline IGL2J genes'; (6)
      'Teleostei IGL2C genes and alleles'; (7) 'FR-IMGT and CDR-IMGT length of the
      Teleostei IGL1V genes', and (8) 'FR-IMGT and CDR-IMGT length of the Teleostei
      IGL2V genes'. These tables are available on the IMGT Marie-Paule page from IMGT,
      the international ImMunoGeneTics database (http://imgt.cines.fr: 8104) created in
      1989 by Marie-Paule Lefranc, Universite Montpellier II, CNRS, France.

PMID- 10899742
TI  - [Publications of dissertations on unconventional medical therapy and diagnosis
      procedures--a contribution to "publication bias"].
AB  - BACKGROUND: The problem of the so-called publication bias has received much
      attention during the last few years. It may be a major threat to the results of
      meta-analyses and systematic reviews. Its implications are not completely clear,
      and successful strategies to deal with this problem are far from being
      established. Some studies have begun to identify characteristic items which de-
      or increase the likelihood of publication of research results. AIM: It was to be
      investigated, whether or not a publication bias can be proved for results of
      medical theses on all kinds of complementary medical subjects and which modifying
      factors can be identified. METHODS: All 140 medical theses on aspects of
      complementary medicine of the years 1982-1992 were included. Data were extracted,
      and publications were searched for in MEDLINE and by personal communication with
      the authors and supervisors. Factors that may influence the likelihood of
      publication were identified by means of bivariate analysis and logistic
      regression analysis. RESULTS: Publications were found for 53 (37,9%) of medical
      theses included. The most dominant factors which were found to influence the
      likelihood of publication were 'positive result' (OR 2.337; 95% CI 0.733; 7.450),
      'high-level statistical analysis' (1.483; 95% CI 0.710; 3.097), 'supervisers with
      a high publication output' (1.477; 95% CI 0.164; 13.267), and 'candidates of
      younger age' (0.691; 95% CI 0.388; 1.230). CONCLUSIONS: As it was found for other
      medical subjects, an apparent publication bias was shown in complementary
      medicine, with positive results having a greater chance of publication than
      negative ones.

PMID- 10899743
TI  - [Effect of sulfur administration on lipid levels, antioxidant status and peroxide
      concentration in health resort patients].
AB  - The aim of the study was to test the effect of drinking sulphurous mineral water
      on lipid status and antioxidative balance in patients with degenerative arthroses
      during a 3-week stay in a health resort. Two groups of patients with and without
      drinking sulphurous water were investigated. Lipid levels, glutathione
      peroxidase, superoxidedismutase, antioxidative status, and peroxide concentration
      in plasma were measured. In both groups similar alterations of the activities of
      antioxidative enzymes as well as peroxide concentrations could be detected.
      Possible specific effects of drinking sulphurous mineral water have to be
      investigated in further studies.

PMID- 10899745
TI  - [Use of conventional and unconventional therapies among patients with ankylosing
      spondylitis].
AB  - OBJECTIVE: A large share of rheumatism patients who are treated by
      rheumatologists use unconventional therapies additionally. What is the frequency
      in patients with ankylosing spondylitis who present for treatment at a radon spa?
      PATIENTS: 75 patients with ankylosing spondylitis presenting for treatment at the
      Gasteiner Heilstollen Hospital agreed to participate in the study (6 refused).
      DESIGN: In an open interview a research assistant asked the patients to name all
      interventions which they have used for the treatment of ankylosing spondylitis.
      RESULTS: Unconventional therapies (beside treatment at the Gasteiner Heilstollen)
      were used by 39 patients. Most frequently cited were acupuncture (15x), diet
      (8x), herbal therapy (7x), and homeopathy (6x). In total 40 different forms of
      unconventional therapies were mentioned. All patients claimed to have used at
      least two conventional therapies. CONCLUSION: Patients presenting for treatment
      at a radon spa claim to have used conventional therapies more frequently than
      unconventional forms of treatment.

PMID- 10899746
TI  - [Gynecologic pain syndrome as psychovegetative and reflex-mediated disorders and
      imbalances].
AB  - Chronic lower abdominal pain without organic findings represent a costly
      diagnostic and therapeutic problem. They are presumably caused by decentralized
      neurovegetative disturbances. Their treatment is a connection between
      somatotherapy and psychotherapy. The manifestations of these disorders are local
      sympathical hypertonia (with algodystrophical vasoconstrictions) or local
      parasympathical hypertonia and amphotonical disturbances with pathological
      vasodilatations, respectively, as well as accompanying disturbances of the local
      lymphatic system. Moreover, non-gynecological causes such as the musculus psoas
      syndrome are often not recognized. Diagnosis of the patient's neurovegetative
      status is an essential prerequisite of treatment. First, a relaxation by
      analgesia should take place, and then whole-body neurovegetative stimulations for
      centralization of the nervous control and, additionally, distant reflex and
      decongestive measures should be performed. For physiotherapeutical purposes, the
      inner genital is reached best via the vagina. In order to change the neural tonus
      of the Frankenhauser ganglions the Vagimoran therapy is the optimal choice. The
      cutivisceral stimulations are applied via the segments S2-S4 and Th10-Th12
      (suprapubical!). In future, chronotherapy in the framework of the imitation
      strategy and the consideration of therapeutical surroundings are essential
      elements of therapy.

PMID- 10899744
TI  - [Efficacy and tolerability of Baldrian versus oxazepam in non-organic and non
      psychiatric insomniacs: a randomised, double-blind, clinical, comparative study].
AB  - OBJECTIVE: To show better improvement of sleep quality when treating non-organic
      insomniacs with extractum Valerianae radix siccum instead of oxazepam. DESIGN:
      Randomised, double blind, comparative study. SETTING: Out-patients of 8 general
      practitioners. PATIENTS: Non-organic and non-psychiatric insomniacs aged between
      18 and 70 years were included into the trial. Persons with known hypersensitivity
      to valerian or benzodiazepines, other psychotropic drugs and various
      contraindications/limitations for benzodiazepines were excluded. INTERVENTION: 75
      patients were randomly allocated either to the index group (2 x 300 mg extractum
      Valerianae radix siccum dragees LI 156) or control group (2 x 5 mg oxazepam
      dragees). The patients took study medication daily over a period of 28 days 30
      min before going to bed. OUTCOMES: The factor sleep quality of the SF-B was
      defined as primary outcome. Secondary outcomes were other sleep characteristics
      of the SF-B, well-being (Bf-S) and anxiety (HAMA). Controls were performed before
      treatment as well as after 1, 2 and 4 weeks. Vital and laboratory parameters as
      well as unexpected events were assessed for safety and tolerability. STATISTICS:
      For all outcomes effect sizes between groups were calculated. For the main
      outcome criteria significance was tested by repeated-measures ANOVA considering
      all cases for which data of at least one follow-up existed (n = 70). RESULTS:
      Baseline characteristics were well balanced. 70% (54/75) of the patients were
      females, over 53% (40/75) reported insomnia for more than 1 year. Mean age was 52
      +/- 12 years. In both groups sleep quality improved significantly (p <0.001), but
      no statistically significant difference could be found between groups (p = 0.70).
      Effect sizes between groups varied between 0.02 and 0.25. Five persons withdrew
      due to possibly adverse drug reactions (2 ( valerian, 3 ( oxazepam). No serious
      adverse events happened. CONCLUSIONS: The study showed no differences in the
      efficacy for valerian and oxazepam. Because of the more favourable adverse effect
      profile of valerian compared to oxazepam, this hypothesis should be analysed
      confirmatorily in an equivalence study.

PMID- 10899747
TI  - [Development of body weight, vegetative autonomous system, and breast cancer].
AB  - In a case-control study the patterns of body mass and autonomic tone in the
      premorbid lifetime of breast cancer patients were analyzed retrospectively.
      Premenopausal breast cancer patients are remarkably thin and show patterns of an
      ergotropic predominance in premorbid lifetime. Their body mass index and
      constitution does not agree with the risk factor 'obesity' and the traditionally
      expected predominance of trophotropy. Furthermore, it turned out that in puberty
      these patients had a discontinuous change of their body weight. As reported at
      the time of diagnosis, in women with postmenopausal breast cancer the risk factor
      'obesity' seems to be true. However, in premorbid lifespan overweight could not
      be detected. Therefore, the independent risk factor 'weight gain' is supposed for
      periclimacteric phase. These women do not show indicators of trophotropic
      predominance but weak signs of ergotropy and eveningness.

PMID- 10899748
TI  - [Mistletoe extracts in the therapy of malignant, hematological and lymphatic
      diseases--a monocentric, retrospective analysis over 16 years].
AB  - OBJECTIVE: The aim of the present investigation was to investigate potentials
      risks of treatment with mistletoe extracts in patients with malignant
      haematological and lymphatic diseases consulting the Tumour Ambulance of the
      Community Hospital Herdecke and to evaluate the therapeutic experiences with this
      treatment. PATIENTS AND METHODS: All 700 patients with these diseases who had
      been counselled at the Tumour Ambulance of Community Hospital Herdecke since the
      foundation of the unit were included in a retrospective questionnaire study to
      collect information on the course of the disease and the survival time. Therapy
      with mistletoe extracts had been recommended to all patients. The treatment was
      carried out by the patient's physician outside the hospital. For inclusion into
      further analysis, information on survival time and mistletoe treatment had to be
      available. Survival times of patients who had actually received the recommended
      mistletoe treatment and of patients who had not received the recommended
      mistletoe treatment were compared (internal comparison). Furthermore, the results
      were compared to those of conventionally treated patients obtained from the
      literature (literature comparison). RESULTS: Of 237 patients for whom sufficient
      data was available, 14 had not been treated with a mistletoe extract. The median
      survival time was 9.18 years among patients who had received mistletoe compared
      to 7.54 years among those without. Before a statistical test was carried out, the
      equivalent distribution of diagnosis in the 2 groups was tested. Regarding this
      criterion, only 205 patients treated with mistletoe extract and 9 patients not
      treated with mistletoe extract could be included into the statistical tests of
      the median survival time. The median survival time was 11.4 years (mistletoe
      patients) and 8.6 years (patients without mistletoe therapy). The difference was
      not significant. There were no cases in which mistletoe treatment was associated
      with deterioration. The comparison with data from the literature yielded very
      similar survival times among patients not treated with mistletoe extract and
      those included in our study. CONCLUSION: No indications to risks of a mistletoe
      therapy on progress of the disease and the survival time could be found.
      Therefore, no ethical reservations should be opposed to future prospective
      investigations of mistletoe therapy in patients with malignant haematological
      diseases.

PMID- 10899749
TI  - [Female constitution--mythologic, historical and developmental psychological
      aspects].
AB  - Our constitution is given to us by predisposition. It always reflects our
      psychological dimension; and it can vary during different phases in our lives.
      Myths are collectively shared fantasies that contribute to the psychological
      stability of both individuals and society. The Antigone myth is regarded as one
      of the rare examples of an independent female protagonist. The historical context
      is important for the comprehension of psychosomatic symptoms surfacing in women
      and men which manifest themselves according to valid medical paradigms and
      historical background. Nowadays, the phase of puberty and adolescence represents
      a prolongation of social adolescence implying a possibility of an individual to
      go through these changes in his or her own rhythm. These chances and
      possibilities allow young females to develop a stable female identity and an
      ability to experience sexuality. In this phase, girls are still confronted with
      the conflict between professional career and performance as self-definition on
      the one hand and family commitment and maternity on the other. This tightrope
      walk between male and female roles can lead to specific wounds in women and even
      in some circumstances to psychosomatic illnesses.

PMID- 10899750
TI  - [The non-scientific time of life and illness].

PMID- 10899751
TI  - Evidence for a founder effect in Sicilian patients with glycogen storage disease
      type II.
AB  - Glycogen storage disease type II (GSD II) is an autosomal recessive inherited
      disorder due to the deficiency of the enzyme acid alpha-glucosidase, which causes
      an accumulation of glycogen in lysosomes. The deletion of exon 18 (delta 18) is a
      frequent mutation associated with a severe phenotype. We analyzed 25 Italian
      patients, 5 of whom were found to be delta 18 carriers. All these 5 patients came
      from Catania, a town in Sicily. We report on the analysis of 5 intragenic single
      point polymorphic markers in the delta 18 patients and on the subsequent
      characterization of a delta 18-associated haplotype. The frequency of this
      haplotype in GSD II patients and normal individuals was 1 and 0.196, respectively
      (chi(2) = 20.9; p < 0.001). The high frequency of the delta 18 allele in this
      Italian subpopulation is likely to be due to a founder effect.

PMID- 10899752
TI  - A complete enumeration and classification of two-locus disease models.
AB  - There are 512 two-locus, two-allele, two-phenotype, fully penetrant disease
      models. Using the permutation between two alleles, between two loci, and between
      being affected and unaffected, one model can be considered to be equivalent to
      another model under the corresponding permutation. These permutations greatly
      reduce the number of two-locus models in the analysis of complex diseases. This
      paper determines the number of nonredundant two-locus models (which can be 102,
      100, 96, 51, 50, or 58, depending on which permutations are used, and depending
      on whether zero-locus and single-locus models are excluded). Whenever possible,
      these nonredundant two-locus models are classified by their property. Besides the
      familiar features of multiplicative models (logical AND), heterogeneity models
      (logical OR), and threshold models, new classifications are added or expanded:
      modifying-effect models, logical XOR models, interference and negative
      interference models (neither dominant nor recessive), conditionally
      dominant/recessive models, missing lethal genotype models, and highly symmetric
      models. The following aspects of two-locus models are studied: the marginal
      penetrance tables at both loci, the expected joint identity-by-descent (IBD)
      probabilities, and the correlation between marginal IBD probabilities at the two
      loci. These studies are useful for linkage analyses using single-locus models
      while the underlying disease model is two-locus, and for correlation analyses
      using the linkage signals at different locations obtained by a single-locus
      model.

PMID- 10899753
TI  - A sib-pair regression model of linkage disequilibrium for quantitative traits.
AB  - A multiple-regression model is described for the detection of linkage
      disequilibrium in quantitative trait loci. The model is developed for application
      to large numbers of single nucleotide polymorphism (SNP) markers genotyped on
      small nuclear families. Parental data are not required by the method, although it
      provides a direct means to test quantitative trait locus-marker allele
      association and to determine whether any such association is attributable to
      linkage disequilibrium or population admixture. Analytical expectations for the
      regression coefficients are derived, allowing direct interpretation of the
      parameter estimates. Simulation studies indicate a substantial improvement in
      power over classical linkage studies of sibling pairs and show the effects of
      population admixture on the model outcomes.

PMID- 10899754
TI  - A measure of phase ambiguity in pairs of SNPs in the presence of linkage
      disequilibrium.
AB  - The extent of haplotype ambiguity in a string of single-nucleotide polymorphisms
      (SNPs) was quantified by Hodge et al. [Nat Genet 1999;21:360]. In their measure,
      the level of ambiguity increases with increasing numbers of loci and as loci
      become more polymorphic. That work assumed linkage equilibrium (LE). However,
      linkage disequilibrium (LD) provides additional information about the haplotypes
      at a site, thereby diluting the level of ambiguity. The ambiguity vanishes
      altogether when LD reaches its maximum value. Here, we introduce the ambiguity
      measure, Phi, to allow for LD (between pairs of SNPs). We derive the formula Phi
      = 4x(2)x(3) for ambiguity in individuals, where x(1), x(2), x(3) and x(4) are the
      probabilities of the A(1)A(2), A(1)B(2), B(1)A(2) and B(1)B(2) haplotypes,
      respectively, and w.l.o.g. x(1)x(4) > or = x(2)x(3). Alternatively, Phi can be
      expressed in terms of the allele frequencies and the LD parameter delta. We also
      extend the formula to triads of two parents plus one child. We estimate our
      measure Phi for relevant SNPs in the published lipoprotein lipase (LPL) gene
      dataset [Clark et al., Am J Hum Genet 1998;63:595; Nickerson et al., Nat Genet
      1998;19:233], obtaining values ranging from a low of 0 to a high of 0.11 among
      adjacent pairs of sites. In genome-wide LD studies to map common disease genes, a
      dense map of SNPs may be utilized to detect association between a marker and
      disease. Therefore, the measurement of ambiguity can potentially help
      investigators to determine a more efficient map, designed to minimize ambiguity
      and subsequent information loss.

PMID- 10899755
TI  - TPH gene may be associated with suicidal behavior, but not with schizophrenia in
      the Korean population.
AB  - Tryptophan hydroxylase (TPH) is a rate-limiting enzyme in the biosynthesis of
      serotonin. This study was designed to examine whether A218C polymorphism, which
      has been identified in intron 7 of the TPH gene, may be associated with
      schizophrenia or the suicidal behavior of schizophrenics in the Korean
      population. TPH genotypes were determined in DNA samples from 217 schizophrenics
      and 236 healthy volunteers. Among the schizophrenic group, 27 patients had a
      history of suicidal behavior. Genomic DNA was amplified by a polymerase-chain
      reaction-based method and restricted by Nhel. A218C polymorphism was associated
      with a history of suicidal behavior in schizophrenics. This finding suggests that
      the TPH gene or a gene in its vicinity may influence suicidal behavior in
      schizophrenics. However, genotypic and allelic distrubutions of this polymorphism
      did not significantly differ between schizophrenics and controls.

PMID- 10899756
TI  - The human HNF-3 genes: cloning, partial sequence and mutation screening in
      patients with impaired glucose homeostasis.
AB  - Hepatocyte nuclear factors 3 (HNF-3 alpha, -3 beta and -3 gamma) belong to an
      evolutionarily conserved family of transcription factors that are critical for
      diverse biological processes such as development, differentiation and metabolism.
      Gene expression studies have shown that HNF3 proteins are critical regulators of
      the early-onset type 2 diabetes genes HNF-1 alpha, HNF-4 alpha and IPF-1/PDX-1
      (MODY3, 1 and 4, respectively) and of glucagon transcription and pancreatic alpha
      cell function. In this study, we investigated whether genetic variation in the
      genes encoding HNF-3 alpha, HNF-3 beta and HNF-3 gamma predisposes humans to
      hyperglycemic or hypoglycemic syndromes. In addition, we report the cloning and
      partial nucleotide sequence of the human HNF-3 alpha, -3 beta and -3 gamma genes.
      Mutation screening included 96 subjects with type 2 diabetes mellitus, as well as
      one family with persistent neonatal hypoglycemia. No functional mutations were
      detected in the coding sequences of the three HNF-3 genes. Our results suggest
      that mutations in HNF-3 genes are not a common cause of type 2 diabetes mellitus.
      The data provided will facilitate genetic studies in other populations and will
      advance our understanding of the role HNF-3 plays in the development of diabetes
      mellitus and other metabolic disorders of glucose homeostasis.

PMID- 10899758
TI  - Plant allergens and pathogenesis-related proteins. What do they have in common?
AB  - In the recent past a great number of proteins causing type 1 allergic reactions
      in humans have been isolated and characterised. The main sources containing
      allergens are plants, mites, fungal spores and insects. Plant-derived allergens
      may either be taken in from the upper respiratory tract or they are present in a
      vast range of plant food causing food allergic reactions. Compared to the
      enormous amount of different plant proteins only a small number out of them are
      identified as a an allergen at present. Looking at the allergen encoding
      sequences, relationships by sequence similarity can be found quite frequently to
      a restricted number of plant protein families. Predominantly, these protein
      families are seed storage proteins, structural proteins and proteins involved in
      the defence-related system - pathogenesis-related proteins. In the following, a
      short overview of a number of pathogenesis-related protein families is presented
      in relation to the already known homologous plant allergens.

PMID- 10899757
TI  - Haptoglobin phenotypes in HIV-1-seropositive patients in Ghana: decreased risk
      for Hp0 individuals.
AB  - Plasma haptoglobin phenotypes were determined by polyacrylamide gel
      electrophoresis, followed by benzidine staining for 58 HIV-1 seropositive
      Ghanaians and 79 randomly selected age-matched controls. Hp0 was present in only
      14% of HIV-1 seropositive individuals compared with more than 40% of the
      controls. The Hp0 individuals showed a highly significant reduced risk for HIV-1
      infection (OR = 0. 21, 95% CI = 0.09-0.51, p = 0.0002). Hp0 may have a protective
      effect in HIV-1 infection.

PMID- 10899759
TI  - The adjuvant effect of particles-importance of genetic background and pre
      sensitisation.
AB  - BACKGROUND: We have previously reported that simple and well-characterised
      particles, such as polystyrene particles (PSP), have an IgE adjuvant effect in
      mice. The purpose of this study was to explore the importance of genetic
      background concerning the adjuvant effect of PSP in different strains of mice.
      METHODS: Inbred NIH/Ola, BALB/c and C3H/HeJ mice were given two intraperitoneal
      injections with either PSP plus OVA or OVA alone, and then an intraperitoneal
      challenge with OVA alone. NIH/Ola mice were also pre-sensitised to develop a weak
      or strong IgE response to OVA, and then given an intraperitoneal challenge with
      PSP plus OVA or OVA alone. Serum levels of total and allergen-specific IgE and
      IgG2a were measured. RESULTS: PSP had a specific IgE and IgG2a adjuvant effect in
      NIH/Ola mice but not in C3H/HeJ and BALB/c mice. Weakly pre-sensitised NIH/Ola
      mice showed the same response pattern as the naive NIH/Ola mice. In contrast,
      strongly pre-sensitised mice showed an antibody response pattern similar to that
      of high-responder BALB/c mice. CONCLUSIONS: Our results indicate that the
      allergen responder status, either genetic or induced, is of importance for the
      adjuvant effect from particles. The IgE and IgG2a adjuvant effect may depend on
      the genetically determined susceptibility of an individual to be influenced by
      exposure to the adjuvant. Therefore, the allergy-enhancing effect from particle
      pollution may differ between individuals.

PMID- 10899760
TI  - Resting B cells are not antigen-presenting cells in the induction of oral
      tolerance of specific Th2 immune responses in mice.
AB  - BACKGROUND: It has been shown that antigen presentation by resting B cells can
      induce tolerance to intravenously administered protein antigens, but the role of
      resting B cells in the induction of oral tolerance is unclear. METHODS: Mice
      continuously treated since birth with rabbit anti-mouse IgM serum for 5 weeks
      were depleted of B cells. When 4 weeks old, B cell-depleted mice drank 10%
      chicken egg white (EW) for 5 days. Ten weeks later, they were immunized with 10
      microgram of ovalbumin in alum and their T helper 2 (Th2) immune responses were
      tested. RESULTS: Th2 cell-mediated IgE and IgG1 antibody responses and spleen
      cell production of IL-4 and IL-5 were suppressed by prior EW feeding during anti
      IgM treatment. When anti-IgM-treated spleen cells collected 1 week after EW
      ingestion were transferred to naive recipients, active suppression of Th2 immune
      responses was also demonstrated. CONCLUSIONS: Although resting small B cells
      aggregate in the mantle zone of follicles of intestinal Peyer's patches, the
      present data suggest that they are not antigen-presenting cells in the induction
      of oral tolerance of Th2 immune responses to oral antigens.

PMID- 10899761
TI  - Activation-induced apoptosis in T cells from young and old Fischer 344 rats.
AB  - BACKGROUND: Activation-induced apoptosis is believed to limit cell proliferation
      and eliminate the high number of activated cells during an immune response.
      METHODS: Activation-induced apoptosis was investigated in splenic T cells
      isolated from young (6 months) and old (24 months) male Fischer 344 rats. The
      cells were incubated with anti-CD3, concanavalin A or staphylococcal enterotoxin
      B (primary stimulus) for 72 h, followed by restimulation with anti-CD3 or
      concanavalin A (secondary stimulus). Apoptosis was assessed by DNA fragmentation
      assay and DNA gel electrophoresis. The expression of the apoptotic marker CD95
      was analyzed by flow cytometry and the relative levels of CD95 ligand, Bcl-2 and
      Bax protein were measured by immunoblotting. RESULTS: It was shown that DNA
      fragmentation was very low in the unstimulated T cells from both young and old
      rats. However, the level of DNA fragmentation was 45-55% greater in the activated
      T cells from old rats than in the activated T cells from young rats. The increase
      in DNA fragmentation was paralleled by an increase in the proportion of cells
      expressing the CD95 molecule. The proportion of CD95+ cells was approximately 40%
      higher in T cells from old rats than in T cells from young rats. In addition, it
      was found that the expression of CD95 ligand and Bax increased and Bcl-2
      decreased in the activated T cells from old rats compared to the activated T
      cells from young rats. CONCLUSION: Our data suggest that the increase in
      sensitivity of T cells to apoptosis with age may contribute to age-associated
      immune dysfunction and disorders.

PMID- 10899762
TI  - Interleukin-4 gene promoter polymorphism [C590T] and asthma in Kuwaiti Arabs.
AB  - BACKGROUND: Recent studies have demonstrated an association of the T allele of a
      promoter polymorphism [C590T] of interleukin-4 (IL-4) gene with asthma/atopy in
      the US and Japanese populations, but data from the UK and Australian families
      failed to find an association. We have investigated the association of this
      [C590T] promoter polymorphism in Kuwaiti Arabs with asthma. METHODS: This study
      included 184 subjects (84 asthmatics and 100 non-asthmatics, 47 of whom were
      totally unrelated normal healthy controls with no history of asthma/atopy in
      three generations of near relatives). The [C590T] promoter polymorphism of the IL
      4 gene was analyzed by a polymerase chain reaction-restriction fragment length
      polymorphism method using the restriction enzyme AvaII. RESULTS: The frequency of
      the T allele was found to be 0.79 in asthmatics, 0.75 in non-asthmatic first
      degree relatives and 0.76 in unrealted controls in Kuwaiti Arabs. No significant
      difference was detected in the distribution of the three genotypes (TT, CT and
      CC) between the asthmatic, non-asthmatic relatives and the unrelated controls.
      The incidence of co-existing phenotypes e.g. hay fever, eczema and a positive
      skin prick test was significantly higher in asthmatics than in the non-asthmatics
      irrespective of the [C590T] genotype. However, within the asthmatic group, a
      higher incidence of eczema was detected in asthmatics with a heterozygous CT
      genotype compared to the asthmatics with a TT genotype. CONCLUSIONS: Our results
      do not show an association between [C590T] promoter polymorphism of the IL-4 gene
      and asthma in Kuwaiti Arabs. Our results are in keeping with the reports from the
      UK and Australian families (no association) but in contrast to the findings from
      US and Japanese populations (an association reported).

PMID- 10899763
TI  - IFN-gamma plays a dominant role in upregulation of Candida-specific IgE synthesis
      in patients with atopic dermatitis.
AB  - BACKGROUND: Although Candida albicans (CA) is known to induce Th1 clones that
      suppress IgE synthesis, serum IgE antibody against CA is often increased in
      atopic patients. This study aims to elucidate the mechanism of IgE synthesis
      against CA in atopic patients. METHODS: We measured the production of IL-4 and
      IFN-gamma by peripheral blood mononuclear cells (PBMCs) from atopic patients upon
      stimulation with CA and examined the correlation with the level of serum IgE
      antibody against CA. RESULTS: The level of serum CA-specific IgE antibody (CA
      IgE) was significantly higher in patients with atopic dermatitis (AD) than in
      patients with bronchial asthma (BA) (geometric mean = 3.6 vs. 0.27 U(A)/ml, p <
      0.02) (U(A) = unit allergen), while there was no difference in the level of house
      dust mite-specific IgE antibody between them (67.6 vs. 87.1 U(A)/ml). Although IL
      4 production by PBMCs upon stimulation with CA in patients with AD was not
      significantly different from that in patients with BA (mean = 359.1 vs. 515.3
      fg/ml), IFN-gamma production was significantly lower in the former than in the
      latter group (8.1 vs. 56.2 pg/ml, p < 0.001). Consequently, the ratio of IL-4/IFN
      gamma production was apparently higher in patients with AD than in those with BA,
      which corresponds to the difference between them in the level of serum CA-IgE. A
      significant negative correlation was seen in patients with AD between IFN-gamma
      production by CA-stimulated PBMCs and the level of serum CA-IgE (p < 0.05).
      CONCLUSIONS: IgE synthesis against CA in atopic patients may be precipitated not
      by enhancing IL-4 production, but by reducing IFN-gamma secretion.

PMID- 10899764
TI  - Eosinophil activation status and corticosteroid responsiveness in severe asthma.
AB  - BACKGROUND: Since eosinophils are implicated in asthma pathogenesis, we
      investigated whether these cells were activated in severe asthma. METHODS: Twenty
      six asthmatics with different clinical responses to oral corticosteroid (CS),
      i.e. sensitive [change in forced expiratory volume in 1 s (DeltaFEV(1)) >/= 25%
      after oral methylprednisolone, 40 mg daily, for 14 days, n = 7], resistant
      (DeltaFEV(1) </= 15%, n = 9) and dependent (>/= 20 mg oral prednisone daily for
      acceptable asthma control, n = 10), were studied. RESULTS: Calcium ionophore
      induced leukotriene (LT) C(4) release of purified blood eosinophils was similar
      in the three groups. Cell incubation with granulocyte-macrophage colony
      stimulating factor (GM-CSF) enhanced ionophore-induced LTC(4) release, and this
      effect was higher in CS-sensitive (5-fold) than in CS-resistant subjects (1.7
      fold) (p = 0.02). CS treatment decreased blood eosinophil counts in these two
      groups of subjects (p </= 0.02) and decreased GM-CSF-enhanced LTC(4) release in
      CS-sensitive asthmatics only (p = 0.04). In contrast, despite a high mean daily
      dose of oral CS (35 +/- 8 mg), blood counts of eosinophils from CS-dependent
      subjects were higher (p = 0.03) and GM-CSF enhancement of LTC(4) release was
      greater (2.8-fold) than in CS-sensitive (2. 1-fold) and CS-resistant (1.7-fold)
      subjects (p = 0.04). Interestingly, serum from CS-resistant subjects reduced GM
      CSF enhancement of LTC(4) release by eosinophils of CS-sensitive asthmatics (p =
      0.001). CONCLUSIONS: Eosinophils from CS-dependent asthmatics have an impaired
      response to CS, whereas serum from CS-resistant subjects contains an inhibitor of
      eosinophil response to GM-CSF.

PMID- 10899765
TI  - Expression of FasL and Fas protein and their soluble form in patients with
      hypersensitivity pneumonitis.
AB  - BACKGROUND: Hypersensitivity pneumonitis (HP) is characterized by a lymphocytic
      alveolitis and loosely formed granulomas in lung biopsy specimens. HP improves or
      disappears altogether after cessation of antigen exposure. The Fas-Fas ligand
      (FasL) system is one of the representative systems of apoptosis-signaling
      receptor molecules, and is involved in various inflammatory diseases. We
      hypothesized that the Fas-FasL system may be associated with this disorder.
      METHODS: We examined the expression of FasL and Fas proteins in lung tissues from
      patients with HP using immunohistochemistry. We also measured the soluble form of
      FasL (sFasL) and sFas levels in serum and bronchoalveolar lavage fluid (BALF)
      from patients with HP using enzyme-linked immunosorbent assay (ELISA).
      Furthermore, we also measured the cytotoxic activity of BALF sFasL in vitro.
      RESULTS: FasL was detected in infiltrating mononuclear cells, and Fas was
      detected in infiltrating mononuclear cells, alveolar macrophages, and epithelioid
      cells in HP, whereas FasL was not detected and Fas was detected in few alveolar
      macrophages in controls. The levels of sFasL and sFas in BALF, but not in serum,
      were significantly increased in HP compared with controls. BALF of HP that
      included high levels of sFasL had no cytotoxic activity for bronchiolar
      epithelial cells in vitro. CONCLUSIONS: In HP, there is an upregulation of FasL
      and Fas in lung tissues. Since there is no incidence of apoptosis and no
      cytotoxic activity for lung epithelial cells in BALF from patients with HP, the
      increased levels of BALF sFasL and sFas may reflect the activation and
      sequestration of inflammatory cells rather than apoptosis.

PMID- 10899766
TI  - Inhibitory effect of wheat germ agglutinin on mouse mast cell adhesion to
      fibronectin.
AB  - BACKGROUND: Mast cells play a critical role in allergic and inflammatory
      responses. The interactions between these cells and extracellular matrix
      components influence the distribution of mast cells in tissues and their
      biological responsiveness. It has been reported that the lectin wheat germ
      agglutinin (WGA) inhibits mast cell mediator release. We decided to investigate
      whether adhesion to fibronectin (FN), another mast cell function, which is
      upregulated following FcepsilonRI cross-linking, is also inhibited by WGA.
      METHODS: Mouse bone-marrow-derived mast cell line MCP5/L was used. For
      FcepsilonRI-dependent mast cell activation, MCP5/L cells were sensitized with
      mouse IgE antibodies. WGA was added to cell suspensions simultaneously with a
      challenging agent and, after an appropriate incubation period, beta
      hexosaminidase release and adhesion to FN were determined. RESULTS: Both
      FcepsilonRI cross-linking-dependent mast cell adhesion to FN and mediator release
      were dose-dependently inhibited by WGA; however, the lectin concentrations
      required to induce maximum inhibition of adhesion were significantly lower.
      Furthermore, WGA inhibited phorbol-myristate-acetate- and A-23187-mediated mast
      cell adhesion to FN, i.e. processes that do not engage FcepsilonRI. The effect of
      WGA on FcepsilonRI-mediated secretion was reversed by GlcNAc. In contrast,
      combination of GlcNAc and NeuNAc or N, N'-diacetylchitobiose was required to
      reverse the inhibitory effect of WGA on mast cell adhesion. CONCLUSION: The
      characteristics of WGA-mediated inhibition of MCP5/L mast cell adhesion to FN
      suggest that mast cell integrins are targets of the inhibitory action of WGA and
      the sugar moieties on these receptors might be important for receptor function.

PMID- 10899767
TI  - A sensitive monoclonal antibody sandwich ELISA for the measurement of the major
      olive pollen allergen Ole e 1.
AB  - BACKGROUND: Olive pollen is a major cause of inhalant allergy in countries around
      the Mediterranean sea. The major allergen of olive pollen is Ole e 1. Measurement
      of the major allergen content of allergen products for diagnosis and therapy is
      becoming an essential element of standardization protocols. This study aimed at
      the development of a monoclonal antibody (mAb) sandwich ELISA for Ole e 1.
      METHODS: Balb/c mice immunized with Ole e 1 were used for the production of mAbs.
      Screening of mice and hybridomas was performed in a RIA with radiolabeled
      purified Ole e 1. Purified mAbs were used as catching and/or (biotinylated)
      detecting antibodies in sandwich ELISA. RESULTS: Four mAbs (IgG1kappa) directed
      to nonoverlapping epitopes on Ole e 1 were obtained: 1A12, 5C1, 10A12 and 3H8.
      Both 1A12 and 10A12 were successfully used for affinity purification of Ole e 1
      from olive pollen extract. Two sandwich ELISAs were developed, with 1A12 and
      10A12 as catching, and 5C1 and 3H8 as detecting antibodies, respectively. Both
      catching and detecting antibodies were used in similar concentrations, ranging
      from 60 to 100 ng/well. For both ELISAs, the sensitivity was approximately 1
      ng/ml of Ole e 1. The measuring range was from 1 to 25 ng/ml. No significant
      differences were observed, when the performance of both ELISAs in standardization
      of olive pollen extracts was compared. CONCLUSIONS: Two sensitive sandwich ELISAs
      for the major olive pollen allergen Ole e 1 were developed. They will prove to be
      useful tools in allergen standardization protocols.

PMID- 10899768
TI  - Mechanisms underlying spontaneous calcium spiking in aequorin-loaded ROS 17/2.8
      cells.
AB  - In earlier studies, McLeod and coworkers reported the detection of spontaneous
      calcium spiking in ROS 17/2.8 cells which they suggested was derived from
      individual cells progressing through mitosis or the cell cycle. They also
      indicated that the degree of spiking could be modulated by exposure of the cells
      to time-varying extremely low frequency electric fields. Given the implications
      of such observations for our understanding of the effects of electromagnetic
      fields on biological systems, it appeared important for mechanistic reasons to
      understand the basis of this spiking. In this study, we were able to confirm that
      spontaneous calcium spiking activity could be detected in ROS 17/2.8 cells and
      that this appeared to emanate from individual cells. We found this spiking to be
      completely dependent on extracellular calcium ions and to be independent of the
      inositol 1,4,5-trisphosphate-sensitive intracellular calcium store. This spiking
      is not reduced by treatments which slow down or block the passage of cells
      through the cell cycle. Further, we found that spiking was only detectable in the
      most highly aequorin-loaded subpopulation of cells whose growth rate is reduced
      and whose morphological appearance is abnormal. In conjunction with what is known
      about calcium spiking in other, nonexcitable mammalian cells in culture, the data
      presented strongly argue that the spontaneous calcium spiking observed in ROS
      17/2.8 cells is unrelated to normal events of the cell cycle and most likely
      result from the damaging effects of excessive loading with aequorin.

PMID- 10899769
TI  - Electromagnetic fields (1.8 GHz) increase the permeability to sucrose of the
      blood-brain barrier in vitro.
AB  - We report an investigation on the influence of high frequency electromagnetic
      fields (EMF) on the permeability of an in vitro model of the blood-brain barrier
      (BBB). Our model was a co-culture consisting of rat astrocytes and porcine brain
      capillary endothelial cells (BCEC). Samples were characterized morphologically by
      scanning electron microscopy and immunocytochemistry. The BBB phenotype of the
      BCEC was shown by the presence of zona occludens protein (ZO-1) as a marker for
      tight junctions and the close contact of the cells together with the absence of
      intercellular clefts. Permeability measurements using (14)C-sucrose indicated a
      physiological tightness which correlated with the morphological findings and
      verified the usefulness of our in vitro model. Samples were exposed to EMF
      conforming to the GSM1800-standard used in mobile telephones (1.8 GHz). The
      permeability of the samples was monitored over four days and compared with
      results of samples that were cultured identically but not exposed to EMF.
      Exposure to EMF increased permeability for (14)C-sucrose significantly compared
      to unexposed samples. The underlying pathophysiological mechanism remains to be
      investigated.

PMID- 10899770
TI  - Description of a new computer wire coding method and its application to evaluate
      potential control selection bias in the Savitz et al. childhood cancer study.
AB  - We developed a new computer wire coding method and then applied it to investigate
      the suggestion that control selection bias might explain the observed association
      between wire codes and childhood cancer made in the study conducted by Savitz et
      al. in the Denver area. The computer wire coding method used a geographic
      information system approach with data on the local distribution electric system
      and from tax assessor records. Individual residences were represented as a circle
      scaled to the ground floor area of the residence and centered on the lot
      centroid. The wire code of the residence was determined from the distance between
      the circle and the relevant power line, and from the current carrying capacity of
      that line. Using this method, wire codes were generated for 238 290 residences
      built before 1986, the time of the Savitz et al. study, in the Denver
      metropolitan area. We then attempted to reconstruct the 1985 population of
      hypothetically eligible control children in the Denver metropolitan area by using
      1980 census data. Since data were not available to locate the children in each
      residence within a census block, uniform, Poisson, and negative binomial
      distributions were used to randomly assign children to residences. To evaluate
      the likelihood of the wire code distribution of the controls selected by Savitz
      et al., 100 random trials were conducted for each distribution, matching two
      controls to each case. The odds ratios between childhood cancer and very high
      current configuration (VHCC) wire codes were reduced when the assigned controls
      were used, suggesting control selection bias may have been present. However,
      control selection bias is unlikely to account for all the reported association
      between childhood cancer and wire codes in the Savitz et al. study.

PMID- 10899771
TI  - Analysis of induced currents in a rat exposed to 50 Hz linearly and circularly
      polarized magnetic fields.
AB  - This paper presents a numerical analysis of currents induced in a rat by linearly
      and circularly polarized magnetic fields of 50 Hz. Special focus was placed on
      pineal gland and retina of rats since these organs were often associated with the
      changes of melatonin synthesis and concentration. Induced currents in two MRI
      based rat models with resolutions of up to 0.125 mm(3) were calculated by using
      the impedance method. We characterized the induced currents by amplitude and
      polarization. Calculated induced current densities were extremely small, i.e., <
      30 microA/m(2) for both linearly and circularly polarized magnetic fields of 1.41
      microT (peak). There were no significant differences in amplitude nor
      polarization of induced currents in the pineal gland between the linearly and the
      circularly polarized magnetic fields when the polarization was in a vertical
      plane. In contrast, the magnetic fields rotating in the horizontal plane produced
      most circularly polarized currents both in the pineal gland and in the retina.

PMID- 10899772
TI  - Biological and morphological effects on the brain after exposure of rats to a
      1439 MHz TDMA field.
AB  - We investigated the effects of exposure to a 1439 MHz TDMA (Time Division
      Multiple Access) field, as used in cellular phones, on the permeability of the
      blood-brain barrier (BBB), on the morphological changes of the brain, and on body
      mass fluctuations. Male Sprague-Dawley (SD) rats were divided into three groups
      of eight rats each. The rats in the EM(+) group, which had their heads arrayed in
      a circle near the central antenna of an exposure system, were exposed to a 1439
      MHz field for one hour a day. The rats in EM(-) group were also in the exposure
      system, however, without high-frequency electromagnetic wave (HF-EMW) exposure.
      The animals in the control group were neither placed in the system nor exposed to
      HF-EMWs. The exposure period was two or four weeks. The energy dose rate peaked
      at 2 W/kg in the brain; the average over the whole body was 0.25 W/kg. The
      changes in the permeability of BBB were investigated by Evans blue injection
      method and by immunostaining of serum albumin. HF-EMWs had no effect on the
      permeability of BBB. The morphological changes in the cerebellum were
      investigated by assessing the degeneration of Purkinje cells and the cell
      concentration in the granular layer. No significant changes were observed in the
      groups of rats exposed to HF-EMWs for two or four weeks. Averaged body masses
      were not affected by HF-EMWs exposure. In conclusion, a 1439 MHz TDMA field did
      not induce observable changes in the permeability of the BBB, morphological
      changes in the cerebellums, or body mass changes in rats, as evaluated by the
      conventional methods.

PMID- 10899773
TI  - Design, optimization, realization, and analysis of an in vitro system for the
      exposure of embryonic stem cells at 1.71 GHz.
AB  - The aim of this study was to develop an exposure system which enables in vitro
      experiments to be conducted under variously modulated radiofrequency exposures.
      Based on the evaluation of different possible systems, it was decided to realize
      a system based on rectangular waveguides. The system was optimized for the
      following parameters: (1) homogeneity of the cell exposure, (2) simultaneous
      exposure of several Petri dishes, (3) efficiency, (4) strict environmental
      control, (5) quick and easy access to the Petri dishes, (6) cost, and (7) simple
      operation by non-engineering personnel. The implemented control software enables
      investigation of a wide spectrum of amplitude modulation schemes between 0.1 Hz
      and 1 kHz, including the modulation schemes of current and future digital mobile
      communication systems as well as other exposure protocols. The system described
      has been initially utilized for a study on the differentiation and cell functions
      of embryonic stem cells. Detailed numerical and experimental dosimetry and
      environmental tests have demonstrated that it meets all target objectives. The
      entire system including the sham exposure system fits into a single incubator. It
      enables the carrying out of various experiments designed to test biological
      responses to RF exposures at 1.2-1.7 GHz by using various modulation schemes and
      long term exposure protocols as well as simultaneous data logging.

PMID- 10899774
TI  - Theoretical evaluation of the distributed power dissipation in biological cells
      exposed to electric fields.
AB  - The paper deals with the power dissipation caused by exposure of biological cells
      to electric fields of various frequencies. With DC and sub-MHz AC frequencies,
      power dissipation in the cell membrane is of the same order of magnitude as in
      the external medium. At MHz and GHz frequencies, dielectric relaxation leads to
      dielectric power dissipation gradually increasing with frequency, and total power
      dissipation within the membrane rises significantly. Since such local increase
      can lead to considerable biochemical and biophysical changes within the membrane,
      especially at higher frequencies, the bulk treatment does not provide a complete
      picture of effects of an exposure. In this paper, we theoretically analyze the
      distribution of power dissipation as a function of field frequency. We first
      discuss conductive power dissipation generated by DC exposures. Then, we focus on
      AC fields; starting with the established first-order model, which includes only
      conductive power dissipation and is valid at sub-MHz frequencies, we enhance it
      in two steps. We first introduce the capacitive properties of the cytoplasm and
      the external medium to obtain a second-order model, which still includes only
      conductive power dissipation. Then we enhance this model further by accounting
      for dielectric relaxation effects, thereby introducing dielectric power
      dissipation. The calculations show that due to the latter component, in the MHz
      range the power dissipation within the membrane significantly exceeds the value
      in the external medium, while in the lower GHz range this effect is even more
      pronounced. This implies that even in exposures that do not cause a significant
      temperature rise at the macroscopic, whole-system level, the locally increased
      power dissipation in cell membranes could lead to various effects at the
      microscopic, single-cell level.

PMID- 10899775
TI  - Experimental low-level direct current therapy in liver metastases: influence of
      polarity and current dose.
AB  - Several authors recently reported on the successful local treatment of malignant
      disease with low-level direct current therapy. However, antitumoral effects in
      colorectal metastases has not been investigated experimentally. The aim of the
      present study was to assess the effectiveness of this therapy and the influence
      of polarity and current dose. Colorectal metastases were established in BD IX
      rats by the injection of colon cancer cells under the liver capsule. After three
      weeks, the liver tumor volumes were determined by magnetic resonance imaging of
      the liver. Low-level direct current therapy was applied via five platinum
      electrodes. Four different applications were used: 60 C/cm(3), anode at the
      center; 60 C/cm(3), cathode at the center; 80 C/cm(3), anode at the center; and
      80 C/cm(3), cathode at the center. In the control group, five electrodes were
      placed without applying any direct current. All animals were sacrificed on
      postoperative day 7. Liver metastases were histologically examined for vital
      tumor cells. Statistical analysis was performed with chi(2)-test. The mean
      initial tumor diameter before treatment was 3.6 +/- 1.4 mm (volume: 25.2 +/- 9.7
      mm(3)). Histological examination of the removed livers revealed significant
      destruction of the metastases with localized necroses in all treatment groups;
      37% had a complete response rate and 63% a partial response rate. There were no
      significant necroses in the control group (P < 0.0001). The best treatment
      results were obtained in the group with an anode at the center and a current dose
      of 80 C/cm(3). Direct current therapy offers a new and safe method for the local
      treatment of liver metastases. We were able to observe that tumor damage is
      related to current dose but not to the polarity of the central electrode.

PMID- 10899776
TI  - Human health consequences of environmentally-modulated gene expression: potential
      roles of ELF-EMF induced epigenetic versus mutagenic mechanisms of disease.
AB  - In order to determine if there might be biological and health consequences after
      exposures to extremely-low frequency electromagnetic fields (ELF-EMF), either
      experimentally or epidemiologically, mechanistic understanding of the potential
      means by which any environmental agent can affect cells in a multicellular
      organism has to be reviewed. The goal of this limited review is to demonstrate
      that, while the prevailing paradigm of the environmentally-induced acute and
      chronic diseases involves either cell killing (cytotoxicity) or gene/chromosome
      mutations (genotoxicity), alteration of the expression of genetic information at
      the transcriptional (turning genes "on" or "off"), translational (stabilizing or
      de-stabilizing the genetic message), or posttranslational (altering the gene
      product or protein) levels has the potential to contribute to various diseases.
      This latter mechanism, "epigenetic" toxicity, unlike the former two which are
      irreversible, is characterized by threshold-like action, multiple biochemical
      pathways and chronic, regular exposures to be effective. Ultimately, epigenetic
      toxicants affect one of four potential cell states, namely alteration of cell
      proliferation, cell differentiation, programmed cell death (apoptosis) or
      adaptive responses of differentiated cells.

PMID- 10899777
TI  - Hatching in zebrafish (Danio rerio) embryos exposed to a 50 Hz magnetic field.
AB  - Zebrafish embryos were exposed intra ovo to a 50 Hz AC magnetic field of 1000
      microT rms, and the progress of asynchronous hatching was monitored. A
      statistically significant delay was observed when field exposure started 48 h
      after fertilization. In contrast, when exposure started 2 h after fertilization,
      no statistically significant effect was seen. When field exposure was
      administered together with submaximal doses of progesterone at 48 h
      postfertilization, the two treatments appeared to delay hatching in an additive
      manner. Evaluating the progress of hatching in zebrafish embryos seems relevant
      for exploration of EMF effects on reproduction.

PMID- 10899779
TI  - Reply: comment by S. milham

PMID- 10899778
TI  - Comment: "Accuracy of industry and occupation on death certificates of electric
      utility workers: implications for epidemiologic studies of magnetic fields and
      cancer" by Kurtis W. Andrews and David Savitz, Bioelectromagnetics 20:512-518
      (1999).

PMID- 10899780
TI  - Ordering of adsorbed proteins.
AB  - Adapting a hard hexagon model to describing protein adsorption, we show by using
      Monte Carlo simulations that the ordering of adsorbed proteins may strongly
      depend on the relative location of the hydrophilic and hydrophobic patches on
      their surface. Specifically, proteins may form dimers, trimers, small rings, and
      zig-zag or straight chains or islands consisting of such fragments.

PMID- 10899781
TI  - Modeling protein density of states: additive hydrophobic effects are insufficient
      for calorimetric two-state cooperativity.
AB  - A well-established experimental criterion for two-state thermodynamic
      cooperativity in protein folding is that the van't Hoff enthalpy DeltaH(vH)
      around the transition midpoint is equal, or very nearly so, to the calorimetric
      enthalpy DeltaH(cal) of the entire transition. This condition is satisfied by
      many small proteins. We use simple lattice models to provide a statistical
      mechanical framework to elucidate how this calorimetric two-state picture may be
      reconciled with the hierarchical multistate scenario emerging from recent
      hydrogen exchange experiments. We investigate the feasibility of using inverse
      Laplace transforms to recover the underlying density of states (i.e., enthalpy
      distribution) from calorimetric data. We find that the constraint imposed by
      DeltaH(vH)/DeltaH(cal) approximately 1 on densities of states of proteins is
      often more stringent than other "two-state" criteria proposed in recent
      theoretical studies. In conjunction with reasonable assumptions, the calorimetric
      two-state condition implies a narrow distribution of denatured-state enthalpies
      relative to the overall enthalpy difference between the native and the denatured
      conformations. This requirement does not always correlate with simple definitions
      of "sharpness" of a transition and has important ramifications for theoretical
      modeling. We find that protein models that assume capillarity cooperativity can
      exhibit overall calorimetric two-state-like behaviors. However, common
      heteropolymer models based on additive hydrophobic-like interactions, including
      highly specific two-dimensional Go models, fail to produce proteinlike
      DeltaH(vH)/DeltaH(cal) approximately 1. A simple model is constructed to
      illustrate a proposed scenario in which physically plausible local and nonlocal
      cooperative terms, which mimic helical cooperativity and environment-dependent
      hydrogen bonding strength, can lead to thermodynamic behaviors closer to
      experiment. Our results suggest that proteinlike thermodynamic cooperativity may
      require a cooperative interplay between local and nonlocal interactions. The
      prospect of using calorimetric data to constrain Z-scores of knowledge-based
      potentials is discussed.

PMID- 10899782
TI  - Structural evidence for recognition of a single epitope by two distinct
      antibodies.
AB  - The structure of a complex between the hemagglutinin of influenza virus and the
      Fab of a neutralizing antibody was determined by X-ray crystallography at 2.8 A
      resolution. This antibody and another which has only 56% sequence identity bind
      to the same epitope with very similar affinities and in the same orientation. One
      third of the interactions is conserved in the two complexes; a significant
      proportion of the interactions that differ are established by residues of the H3
      complementarity-determining regions (CDR) which adopt distinct conformations in
      the two antibodies. This demonstrates that there is a definite flexibility in the
      selection of antibodies that bind to a given epitope, despite the high affinity
      of their complexes. This flexibility allows the humoral immune response to be
      redundant, a feature that may be useful in achieving longer lasting protection
      against evolving viral pathogens.

PMID- 10899783
TI  - Hydrogen exchange study of canine milk lysozyme: stabilization mechanism of the
      molten globule.
AB  - The native state (1)H, (15)N resonance assignment of 123 of the 128 nonproline
      residues of canine milk lysozyme has enabled measurements of the amide hydrogen
      exchange of over 70 amide hydrogens in the molten globule state. To elucidate the
      mechanism of protein folding, the molten globule state has been studied as a
      model of the folding intermediate state. Lysozyme and alpha-lactalbumin are
      homologous to each other, but their equilibrium unfolding mechanisms differ.
      Generally, the folding mechanism of lysozyme obeys a two-state model, whereas
      that of alpha-lactalbumin follows a three-state model. Exceptions to this rule
      are equine and canine milk lysozymes, which exhibit a partially unfolded state
      during the equilibrium unfolding; this state resembles the molten globule state
      of alpha-lactalbumin but with extreme stability. Study of the molten globules of
      alpha-lactalbumin and equine milk lysozyme showed that the stabilities of their
      alpha-helices are similar, despite the differences in the thermodynamic stability
      of their molten globule states. On the other hand, our hydrogen exchange study of
      the molten globule of canine milk lysozyme showed that the alpha-helices are more
      stabilized than in alpha-lactalbumin or equine milk lysozyme and that this
      enhanced stability is caused by the strengthened cooperative interaction between
      secondary structure elements. Thus, our results underscore the importance of the
      cooperative interaction in the stability of the molten globule state.

PMID- 10899784
TI  - Adrenodoxin: structure, stability, and electron transfer properties.
AB  - Adrenodoxin is an iron-sulfur protein that belongs to the broad family of the
      [2Fe-2S]-type ferredoxins found in plants, animals and bacteria. Its primary
      function as a soluble electron carrier between the NADPH-dependent adrenodoxin
      reductase and several cytochromes P450 makes it an irreplaceable component of the
      steroid hormones biosynthesis in the adrenal mitochondria of vertebrates. This
      review intends to summarize current knowledge about structure, function, and
      biochemical behavior of this electron transferring protein. We discuss the
      recently solved first crystal structure of the vertebrate-type ferredoxin, the
      truncated adrenodoxin Adx(4-108), that offers the unique opportunity for better
      understanding of the structure-function relationships and stabilization of this
      protein, as well as of the molecular architecture of [2Fe-2S] ferredoxins in
      general. The aim of this review is also to discuss molecular requirements for the
      formation of the electron transfer complex. Essential comparison between
      bacterial putidaredoxin and mammalian adrenodoxin will be provided. These
      proteins have similar tertiary structure, but show remarkable specificity for
      interactions only with their own cognate cytochrome P450. The discussion will be
      largely centered on the protein-protein recognition and kinetics of adrenodoxin
      dependent reactions.

PMID- 10899785
TI  - Structural and functional properties of a Bacillus subtilis temperature-sensitive
      sigma(A) factor.
AB  - Bacillus subtilis DB1005 is a temperature-sensitive (Ts) sigA mutant containing
      double-amino-acid substitutions (I198A and I202A) on the hydrophobic face of the
      promoter -10 binding helix of sigma(A) factor. We have analyzed the structural
      and functional properties of this mutant sigma(A) factor both in vivo and in
      vitro. Our data revealed that the Ts sigma(A) factor possessed predominantly a
      multimeric structure which was prone to aggregation at restrictive temperature.
      The extensive aggregation of the Ts sigma(A) resulted in a very low core-binding
      activity of the Ts sigma(A) factor and a markedly reduced sigma(A)-RNA polymerase
      activity in B. subtilis DB1005, suggesting that extensive aggregation of the Ts
      sigma(A) is the main trigger for the temperature sensitivity of B. subtilis
      DB1005. Partial proteolysis, tryptophan fluorescence and 1-anilinonaphthalene-8
      sulfonate-binding analyses revealed that the hydrophobic face of the promoter -10
      binding helix and also the hydrophobic core region of the Ts sigma(A) factor were
      readily exposed on the protein surface. This hydrophobic exposure provides an
      important cue for mutual interaction between molecules of the Ts sigma(A) and
      allows the formation of multimeric Ts sigma(A). Our results also indicate that
      Ile-198 and Ile-202 on the hydrophobic face of the promoter -10 binding helix are
      essential to ensure the correct folding and stabilization of the functional
      structure of sigma(A) factor.

PMID- 10899786
TI  - Similarity-driven flexible ligand docking.
AB  - A similarity-driven approach to flexible ligand docking is presented. Given a
      reference ligand or a pharmacophore positioned in the protein active site, the
      method allows inclusion of a similarity term during docking. Two different
      algorithms have been implemented, namely, a similarity-penalized docking (SP
      DOCK) and a similarity-guided docking (SG-DOCK). The basic idea is to maximally
      exploit the structural information about the ligand binding mode present in cases
      where ligand-bound protein structures are available, information that is usually
      ignored in standard docking procedures. SP-DOCK and SG-DOCK have been derived as
      modified versions of the program DOCK 4.0, where the similarity program MIMIC
      acts as a module for the calculation of similarity indices that correct docking
      energy scores at certain steps of the calculation. SP-DOCK applies similarity
      corrections to the set of ligand orientations at the end of the ligand
      incremental construction process, penalizing the docking energy and, thus, having
      only an effect on the relative ordering of the final solutions. SG-DOCK applies
      similarity corrections throughout the entire ligand incremental construction
      process, thus affecting not only the relative ordering of solutions but also
      actively guiding the ligand docking. The performance of SP-DOCK and SG-DOCK for
      binding mode assessment and molecular database screening is discussed. When
      applied to a set of 32 thrombin ligands for which crystal structures are
      available, SG-DOCK improves the average RMSD by ca. 1 A when compared with DOCK.
      When those 32 thrombin ligands are included into a set of 1,000 diverse molecules
      from the ACD, DIV, and WDI databases, SP-DOCK significantly improves the
      retrieval of thrombin ligands within the first 10% of each of the three databases
      with respect to DOCK, with minimal additional computational cost. In all cases,
      comparison of SP-DOCK and SG-DOCK results with those obtained by DOCK and MIMIC
      is performed.

PMID- 10899787
TI  - Polymer principles of protein calorimetric two-state cooperativity.
AB  - The experimental calorimetric two-state criterion requires the van't Hoff
      enthalpy DeltaH(vH) around the folding/unfolding transition midpoint to be equal
      or very close to the calorimetric enthalpy DeltaH(cal) of the entire transition.
      We use an analytical model with experimental parameters from chymotrypsin
      inhibitor 2 to elucidate the relationship among several different van't Hoff
      enthalpies used in calorimetric analyses. Under reasonable assumptions, the
      implications of these DeltaH(vH)'s being approximately equal to DeltaH(cal) are
      equivalent: Enthalpic variations among denatured conformations in real proteins
      are much narrower than some previous lattice-model estimates, suggesting that the
      energy landscape theory "folding to glass transition temperature ratio" T(f)
      /T(g) may exceed 6.0 for real calorimetrically two-state proteins. Several
      popular three-dimensional lattice protein models, with different numbers of
      residue types in their alphabets, are found to fall short of the high
      experimental standard for being calorimetrically two-state. Some models postulate
      a multiple-conformation native state with substantial pre-denaturational
      energetic fluctuations well below the unfolding transition temperature, or
      predict a significant post-denaturational continuous conformational expansion of
      the denatured ensemble at temperatures well above the transition point, or both.
      These scenarios either disagree with experiments on protein size and dynamics, or
      are inconsistent with conventional interpretation of calorimetric data. However,
      when empirical linear baseline subtractions are employed, the resulting
      DeltaH(vH)/DeltaH(cal)'s for some models can be increased to values closer to
      unity, and baseline subtractions are found to correspond roughly to an
      operational definition of native-state conformational diversity. These results
      necessitate a re-assessment of theoretical models and experimental
      interpretations.

PMID- 10899788
TI  - Recurrent oligomers in proteins: an optimal scheme reconciling accurate and
      concise backbone representations in automated folding and design studies.
AB  - A novel scheme is introduced to capture the spatial correlations of consecutive
      amino acids in naturally occurring proteins. This knowledge-based strategy is
      able to carry out optimally automated subdivisions of protein fragments into
      classes of similarity. The goal is to provide the minimal set of protein
      oligomers (termed "oligons" for brevity) that is able to represent any other
      fragment. At variance with previous studies in which recurrent local motifs were
      classified, our concern is to provide simplified protein representations that
      have been optimised for use in automated folding and/or design attempts. In such
      contexts, it is paramount to limit the number of degrees of freedom per amino
      acid without incurring loss of accuracy of structural representations. The
      suggested method finds, by construction, the optimal compromise between these
      needs. Several possible oligon lengths are considered. It is shown that
      meaningful classifications cannot be done for lengths greater than six or smaller
      than four. Different contexts are considered for which oligons of length five or
      six are recommendable. With only a few dozen oligons of such length, virtually
      any protein can be reproduced within typical experimental uncertainties.
      Structural data for the oligons are made publicly available.

PMID- 10899789
TI  - Characterization of the active site of group B streptococcal hyaluronan lyase
AB  - Xin Li was inadvertently dropped from the list of authors for this article. The
      authors regret this error.

PMID- 10899790
TI  - Heralding EarlyView(R)!

PMID- 10899791
TI  - Overview: normal and abnormal human brain development.

PMID- 10899792
TI  - Pathophysiology, prevention, and potential treatment of neural tube defects.
AB  - Neural tube defects (NTD) remain a major cause of morbidity in spite of the
      reduction in liveborn incidence with periconceptional folic acid. However, the
      etiology remains unknown. This article reviews studies that address causation and
      potential treatment of NTD in humans and in animal models that resemble aspects
      of the common human NTD. Studies of nutritional markers of vitamin B12 and folic
      acid support a defect in homocysteine metabolism; a thermolabile variant of
      methylene tetrahydrofolate reductase, an enzyme that remethylates homocysteine to
      methionine, correlates with a risk of NTD in some human populations. Numerous
      mouse mutant models of NTD exist, attesting to the ease of disruption of
      neurulation, and a genetic basis for this malformation. Of these models, the
      curly tail mouse mutant most closely resembles the common human NTD. Folic acid
      does not prevent NTD in this model; however inositol supplementation does result
      in a significant reduction in incidence. Recent advances in fetal surgery, and
      evidence from mechanically created myelomeningocele in large animals amenable to
      surgical intervention suggest that the handicaps associated with myelomeningocele
      and associated Chiari Type II malformation may be prevented by in utero NTD
      closure. Success will depend on preservation of neurological tissue until such
      intervention is possible. Further research in animal models at the genetic and
      cellular levels, together with technological surgical advances, provide hope that
      prevention of more NTD and the associated handicaps may be possible. MRDD
      Research Reviews 6:6-14, 2000.

PMID- 10899793
TI  - Genetic approaches to understanding brain development: holoprosencephaly as a
      model.
AB  - Holoprosencephaly (HPE) is the most common major developmental defect of the
      forebrain in humans. Clinical expression is variable, ranging from a small brain
      with a single cerebral ventricle and cyclopia to clinically unaffected carriers
      in familial HPE. Significant etiologic heterogeneity exists in HPE and includes
      both genetic and environmental causes. Defects in the cell signaling pathway
      involving the Sonic Hedgehog (SHH) gene, as well as defects in the cholesterol
      biosynthesis have been shown to cause HPE in humans. More recently, HPE genes
      from additional signaling pathways have been identified. These discoveries and
      current genetic approaches serve as a paradigm for studying normal and abnormal
      brain morphogenesis. MRDD Research Reviews 6:15-21, 2000.

PMID- 10899794
TI  - Neocortical malformation as consequence of nonadaptive regulation of
      neuronogenetic sequence.
AB  - Variations in the structure of the neocortex induced by single gene mutations may
      be extreme or subtle. They differ from variations in neocortical structure
      encountered across and within species in that these "normal" structural
      variations are adaptive (both structurally and behaviorally), whereas those
      associated with disorders of development are not. Here we propose that they also
      differ in principle in that they represent disruptions of molecular mechanisms
      that are not normally regulatory to variations in the histogenetic sequence. We
      propose an algorithm for the operation of the neuronogenetic sequence in relation
      to the overall neocortical histogenetic sequence and highlight the restriction
      point of the G1 phase of the cell cycle as the master regulatory control point
      for normal coordinate structural variation across species and importantly within
      species. From considerations based on the anatomic evidence from neocortical
      malformation in humans, we illustrate in principle how this overall sequence
      appears to be disrupted by molecular biological linkages operating principally
      outside the control mechanisms responsible for the normal structural variation of
      the neocortex. MRDD Research Reviews 6:22-33, 2000.

PMID- 10899795
TI  - Genetics of neuronal migration in the cerebral cortex.
AB  - The development of the cerebral cortex requires large-scale movement of neurons
      from areas of proliferation to areas of differentiation and adult function in the
      cortex proper, and the patterns of this neuronal migration are surprisingly
      complex. The migration of neurons is affected by several naturally occurring
      genetic defects in humans and mice; identification of the genes responsible for
      some of these conditions has recently yielded new insights into the mechanisms
      that regulate migration. Other key genes have been identified via the creation of
      induced mutations that can also cause dramatic disorders of neuronal migration.
      However, our understanding of the physiological and biochemical links between
      these genes is still relatively spotty. A number of molecules have also been
      studied in mice (Reelin, mDab1, and the VLDL and ApoE2 receptors) that appear to
      represent part of a coherent signaling pathway that regulates migration, because
      multiple genes cause an indistinguishable phenotype when mutated. On the other
      hand, two human genes that cause lissencephaly (LIS1, DCX) encode proteins that
      have recently been implicated as regulators or microtubule dynamics. This article
      reviews some of the mutant phenotypes in light of the mechanisms of neuronal
      migration. MRDD Research Reviews 6:34-40, 2000.

PMID- 10899796
TI  - Biology and pathobiology of neuronal development.
AB  - Differentiation of neurons within the central nervous system occurs by the
      combined effects of intrinsic genetic programs and epigenetic stimuli. Disorders
      causing mental retardation and other abnormalities of higher cortical function
      arise by disturbances of the normal developmental sequence. MRDD Research Reviews
      6:41-46, 2000.

PMID- 10899797
TI  - Myelin and disorders that affect the formation and maintenance of this sheath.

PMID- 10899798
TI  - In vivo studies of brain development by magnetic resonance techniques.
AB  - Understanding of the morphological development of the human brain has largely
      come from neuropathological studies obtained postmortem. Magnetic resonance (MR)
      techniques have recently allowed the provision of detailed structural, metabolic,
      and functional information in vivo on the human brain. These techniques have been
      utilized in studies from premature infants to adults and have provided invaluable
      data on the sequence of normal human brain development. This article will focus
      on MR techniques including conventional structural MR imaging techniques,
      quantitative morphometric MR techniques, diffusion weighted MR techniques, and MR
      spectroscopy. In order to understand the potential applications and limitations
      of MR techniques, relevant physical and biological principles for each of the MR
      techniques are first reviewed. This is followed by a review of the understanding
      of the sequence of normal brain development utilizing these techniques. MRDD
      Research Reviews 6:59-67, 2000.

PMID- 10899799
TI  - Developmental neuroimaging of children using magnetic resonance techniques.
AB  - Cognitive and motor development in children remain fascinating processes that are
      uniquely human. Progress has been made in recent years in elucidating the
      prenatal process of human brain development. In addition, much information exists
      regarding the behavioral aspects of postnatal human development. However, little
      is known about the relationship between anatomic postnatal central nervous system
      development and the accretion of functional milestones observed in children from
      the neonatal period through adolescence. Recently, powerful qualitative and
      quantitative magnetic resonance techniques have been developed that will permit
      detailed inquiry into the connection between the developing brain and the
      developing mind. In this review, first, the steps of prenatal and postnatal brain
      development are reviewed briefly. Subsequently, recent magnetic resonance imaging
      data related to human brain development during the fetal, neonatal, and later
      childhood periods are presented. Finally, functional magnetic resonance imaging
      (fMRI) is discussed. Specific examples of its usefulness are provided. Magnetic
      resonance imaging techniques such as quantitative MRI, volumetric MRI, diffusion
      tensor imaging, and functional magnetic resonance imaging (fMRI) when combined
      with neurologic and neuropsychologic evaluation, will provide new insights into
      the cognitive development of children. MRDD Research Reviews 6:68-80, 2000.

PMID- 10899800
TI  - Overview: specific behavioral/cognitive phenotypes of genetic disorders.

PMID- 10899801
TI  - Behavioral phenotype of individuals with Down syndrome.
AB  - Evidence is reviewed for a developmentally-emerging behavioral phenotype in
      individuals with Down syndrome that includes significant delay in nonverbal
      cognitive development accompanied by additional, specific deficits in speech,
      language production, and auditory short-term memory in infancy and childhood, but
      fewer adaptive behavior problems than individuals with other cognitive
      disabilities. Evidence of dementia emerges for up to half the individuals studied
      after age 50. Research issues affecting control group selection in establishing
      phenotypic characteristics are discussed, as well as the possible genetic
      mechanisms underlying variation in general cognitive delay, specific language
      impairment, and adult dementia. MRDD Research Reviews 2000;6:84-95. Wiley-Liss,
      Inc.

PMID- 10899802
TI  - Advances in research on the fragile X syndrome.
AB  - Fragile X syndrome is a neurodevelopmental disorder that results from a single
      gene mutation on the X chromosome. The purpose of this review is to summarize key
      advances made in understanding the fragile X premutation gene seen in carriers
      and the full mutation gene seen in persons with the syndrome. DNA testing has
      replaced cytogenetic testing as the primary method for identification of fragile
      X, although the efficacy of protein level screening is being explored. The
      premutation is associated with no effects, although there is evidence of physical
      effects-primarily premature menopause and mild outward features of the fragile X
      syndrome-among premutation carriers. There is much controversy regarding
      premutation effects on psychological development. The few experimental studies
      carried out to date do not suggest noticeable or significant effects. One
      challenge in addressing this controversy is the sometimes ambiguous
      differentiation between premutation and full mutation genes. There is a well
      established yet highly variable phenotype of the full mutation. Research from
      this decade has helped to address specific aspects of this phenotype, including
      the early course of its development in males, the influence of home and family
      environments, the nature of social difficulties and autistic features seen in
      boys and girls with fragile X, and the potential role of hyperarousal or hyper
      reactivity. Studies in these areas, and on the role of FMR protein, will
      contribute towards ongoing advances in our understanding of fragile X syndrome
      and its mechanisms. The variability in physical, social, and cognitive features,
      as described in this review, is one that prohibits clear-cut screening guidelines
      designed to avoid high rates of both false positives and false negatives. Results
      from recent studies indicate the need to consider behavioral features in
      selecting candidates for fragile X screening. MRDD Research Reviews 2000;6:96
      106.

PMID- 10899803
TI  - Neurobehavioral phenotype of Klinefelter syndrome.
AB  - A defined genetic syndrome with neurobehavioral components offers an unusual
      paradigm for the correlation of genetic defects with neurodevelopmental
      abnormalities. The power of the combination of detailed behavioral,
      neuroanatomical, and genetic studies has been demonstrated in studies of other
      conditions involving the sex chromosomes, such as Fragile X syndrome (Mazzocco
      [2000] Ment Retard Develop Disabil Res Rev. 6:96-106) and Turner syndrome (Ross
      [2000] Ment Retard Develop Disabil Res Rev. 6:135-141). Although the behavioral
      and neurologic difficulties that have been identified in Klinefelter syndrome
      (KS) are in most cases milder than the consequences of many other genetic
      syndromes, the deficits in KS cause significant morbidity, representing a more
      common, but poorly understood, subtype of those with learning disabilities. Both
      as children and as adults, KS subjects appear to offer a powerful genetic model
      for the study of language and language-based learning disabilities. Although it
      has been proposed that the language-based learning difficulties of KS boys are
      similar to those of nonaneuploidic dyslexics [Bender et al., 1986; Geschwind et
      al., 1998], this is not yet well established. The co-morbid frontal-executive
      dysfunction observed in KS is also a likely contributor to learning difficulties
      and, perhaps, social cognition, in many KS patients. It is also proposed that
      altered left-hemisphere functioning, whether causing, or due to, altered
      functional and anatomical cerebral dominance, is at the core of KS subjects'
      language problems. Although X chromosomal loci can provide only part of the
      picture, the study of KS subjects, a population with a relatively homogeneous
      etiology for dyslexia/dysphasia and frontal-executive dysfunction, offers many
      advantages over such a study in the general population, in which both dyslexia
      and attentional disorders are quite genetically heterogeneous [Decker and Bender,
      1988; Pennington, 1990; Grigorenko et al., 1997; Geschwind et al., 1998].
      Furthermore, the interaction of genetic factors and hormonal influences in the
      cognitive phenotypes described remains an unexplored area for future
      investigation. MRDD Research Reviews 2000;6:117-124.

PMID- 10899804
TI  - Behavioral phenotype of neurofibromatosis, type 1.
AB  - Neurofibromatosis, type 1 (NF1) is a very common inherited disorder that was
      first described in the late 19th century. NF1 is associated with a myriad of
      behavioral manifestations in addition to its frequent and often severe medical
      and physical complications. Learning disability, cognitive impairment, emotional
      and psychosocial difficulties have been reported so frequently in
      neurofibromatosis that these are often considered hallmarks. This report briefly
      introduces the medical and physical characteristics of NF1. We then detail the
      behavioral manifestations of NF1 with additional discussion of possible
      etiologies for the high incidence of these behavioral difficulties. MRDD Research
      Reviews 2000;6:117-124.

PMID- 10899805
TI  - Appetitive behavior, compulsivity, and neurochemistry in Prader-Willi syndrome.
AB  - Advances in genetic research have led to an increased understanding of genotype
      phenotype relationships. Excessive eating and weight gain characteristic of
      Prader-Willi syndrome (PWS) have been the understandable focus of much of the
      research. The intense preoccupation with food, lack of satiation, and incessant
      food seeking are among the most striking features of PWS. It has become
      increasingly clear that the behavioral phenotype of PWS also includes symptoms
      similar to obsessive compulsive disorder, which in all probability interact with
      the incessant hunger and lack of satiation to engender the intense preoccupation
      and food seeking behavior that is characteristic of this disorder. Several lines
      of evidence suggest that genetic material on chromosome 15 may alter synthesis,
      release, metabolism, binding, intrinsic activity, or reuptake of specific
      neurotransmitters, or alter the receptor numbers and/or distribution involved in
      modulating feeding. Among the likely candidates are GABAnergic, serotonergic, and
      neuropeptidergic mechanisms. This review summarizes what is known about the
      appetitive behavior and compulsivity in PWS and discusses the possible mechanisms
      underlying these behaviors. MRDD Research Reviews 2000;6:125-130.

PMID- 10899806
TI  - Behavioral phenotype of RSH/Smith-Lemli-Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS, RSH/SLO syndrome, MIM 270400) is an autosomal
      recessive multiple malformation/mental retardation syndrome initially described
      by Smith et al. [1964] that is due to a defect in cholesterol biosynthesis. The
      behavioral phenotype of Smith-Lemli-Opitz syndrome demonstrates cognitive
      abilities from borderline intellectual functioning to profound mental
      retardation, sensory hyperreactivity, irritability, language impairment, sleep
      cycle disturbance, self-injurious behavior, and autism spectrum behaviors. In a
      recent study of 28 subjects, 14 subjects (50%) with SLOS also exhibited the
      behavior of throwing themselves backward in a characteristic upper body movement
      ("opisthokinesis") and 2 adolescents had a stretching motion of the upper body
      accompanied by hand flicking [Tierney et al., 1999]. In that same study, 6 of 13
      subjects (46%) met the Autism Diagnostic Interview-Revised (ADI-R) algorithm
      criteria (Lord et al. [1993] Infant Mental Health 14:234-252; Lord et al. [1994]
      J Autism Dev Disord 24:659-685) and the Diagnostic and Statistical Manual (APA
      [1994] DSM-IV) diagnostic criteria for autistic disorder. Smith-Lemli-Opitz
      syndrome is a metabolic disorder that is associated with autism. MRDD Research
      Reviews 2000;6:131-134.

PMID- 10899807
TI  - Neurodevelopmental and psychosocial aspects of Turner syndrome.
AB  - Turner syndrome (TS) is the complex phenotype of human females with complete or
      partial absence of the second sex chromosome, or monosomy X. A characteristic
      neurocognitive and psychosocial profile has also been described in TS females.
      Typically, specific deficits in visual-spatial/perceptual abilities, nonverbal
      memory function, motor function, executive function, and attentional abilities
      occur in TS children and adults of varying races and socioeconomic status. TS
      associated psychosocial difficulties occur in the areas of maturity and social
      skills. We hypothesize that a subset of the neurocognitive deficits (visual
      spatial/perceptual abilities) are genetically determined and result from abnormal
      expression of one or more X chromosome genes. In addition, a different subset of
      these neurocognitive deficits (memory, reaction time, and speeded motor function)
      result from estrogen deficiency and are at least somewhat reversible with
      estrogen treatment. The TS-associated psychosocial problems are most likely
      linked to these core neurocognitive deficits and do not reflect a separate and
      independent component of the syndrome. Turner syndrome research has progressed
      significantly over the last decade. The field has moved from descriptive reports
      based on single individuals or small clinical samples to the use of experimental
      designs with larger, more diverse and representative samples. This degree of
      variability among individuals with Turner syndrome in all domains (karyotype or
      genetic constitution, physical attributes, neurocognitive and social functioning)
      suggests the need to identify risk and protective factors contributing to the
      heterogeneity in the phenotype. Active education about TS and participation in
      patient advocacy groups such as the Turner Syndrome Society of the United States
      (http://www. turner-syndrome-us.org/) has provided new information for TS adults
      and families as well as a supportive peer group. MRDD Research Reviews 2000;6:135
      141.

PMID- 10899808
TI  - Velo-cardio-facial syndrome: a distinctive behavioral phenotype.
AB  - Velo-cardio-facial syndrome (VCFS) is the most common contiguous gene disorder
      and one of the most common multiple anomaly syndromes in humans. Over 180
      anomalies have been delineated in the syndrome; the most common of which are the
      behavioral manifestations. Learning disabilities, psychiatric illness, attention
      deficit disorder, and a variety of developmental disorders are nearly ubiquitous
      findings in VCFS and are not mutually exclusive, often overlapping to create a
      distinctive yet confusing phenotypic picture. In addition, standard treatments
      for each of these separate clinical findings may not be effective, and may even
      be potentially harmful in individuals with VCFS, such as the use of stimulants
      for hyperactivity. VCFS is caused by a small deletion of DNA from the long arm of
      chromosome 22. Researchers are currently studying the deletion located at 22q11.2
      because of the possibility that a firm genetic link to psychiatric illness and
      learning disorders may be found. This report describes the behavioral
      manifestations of VCFS, emphasizing the overlap between the cognitive and
      psychiatric disorders that are so common in this syndrome. MRDD Research Reviews
      2000;6:142-147.

PMID- 10899809
TI  - Williams syndrome: cognition, personality, and adaptive behavior.
AB  - Williams syndrome is caused by a microdeletion of at least 16 genes on chromosome
      7q11.23. The syndrome results in mild to moderate mental retardation or learning
      disability. The behavioral phenotype for Williams syndrome is characterized by a
      distinctive cognitive profile and an unusual personality profile. Relative to
      overall level of intellectual ability, individuals with Williams syndrome
      typically show a clear strength in auditory rote memory, a strength in language,
      and an extreme weakness in visuospatial construction. The personality of
      individuals with Williams syndrome involves high sociability, overfriendliness,
      and empathy, with an undercurrent of anxiety related to social situations. The
      adaptive behavior profile for Williams syndrome involves clear strength in
      socialization skills (especially interpersonal skills related to initiating
      social interaction), strength in communication, and clear weakness in daily
      living skills and motor skills, relative to overall level of adaptive behavior
      functioning. Literature relevant to each of the components of the Williams
      syndrome behavioral phenotype is reviewed, including operationalizations of the
      Williams syndrome cognitive profile and the Williams syndrome personality
      profile. The sensitivity and specificity of these profiles for Williams syndrome,
      relative to individuals with other syndromes or mental retardation or borderline
      normal intelligence of unknown etiology, is considered. The adaptive behavior
      profile is discussed in relation to the cognitive and personality profiles. The
      importance of operationalizations of crucial components of the behavioral
      phenotype for the study of genotype/phenotype correlations in Williams syndrome
      is stressed. MRDD Research Reviews 2000;6:148-158.

PMID- 10899810
TI  - Evolving European GM regulation: an example of biopolitics at work.

PMID- 10899811
TI  - Recombinant DNA insertion into plant retrotransposons.

PMID- 10899812
TI  - Biotechnology, inquiry, and public education.
AB  - Education of our children is arguably society's most important task, profoundly
      shaping the communities in which we all live. Achievement and success in many
      facets of our culture depend critically on formal education. Education is widely
      perceived as the only viable weapon against the poverty, drug abuse, crime and
      teenage pregnancy that derail many citizens, particularly in the inner cities,
      from realizing their productive human potential. Beyond its value to individuals,
      education is the cornerstone of societal advancement.

PMID- 10899813
TI  - XML: a lingua franca for science?
AB  - XML is a new language designed to solve one of the biggest problems of the World
      Wide Web: its main language, HTML, is not extensible. In this article, the
      authors discuss the current successes and limitations of the World Wide Web,
      briefly explain the basics of XML and present the benefits of using XML as a data
      exchange language. Finally, they discuss real-life applications that have been
      developed using XML, with a focus on biology.

PMID- 10899814
TI  - A SNPshot: pharmacogenetics and the future of drug therapy.
AB  - Pharmacogenetics holds great promise for the optimization of new drug development
      and the individualization of clinical therapeutics in the 21st century. In this
      brief review, we trace the historical roots of pharmacogenetics, discuss its
      rapidly evolving processes and paradigms, and look towards future applications of
      pharmacogenetics in enhancing the efficiency of the drug development pipeline and
      in improving patient care.

PMID- 10899815
TI  - Biocatalytic membrane reactors: applications and perspectives.
AB  - Membranes and biotechnological tools can be used for improving traditional
      production systems to maintain the sustainable growth of society. Typical
      examples include: new and improved foodstuffs, in which the desired nutrients are
      not lost during thermal treatment; novel pharmaceutical products with well
      defined enantiomeric compositions; and the treatment of waste-water, wherein
      pollution by traditional processes is a problem.

PMID- 10899816
TI  - RNA as a drug target: methods for biophysical characterization and screening.
AB  - RNA folds into complex structures that can interact specifically with effector
      proteins. These interactions are essential for various biological functions. In
      order to discover small molecules that can affect important RNA-protein
      complexes, a thorough analysis of the thermodynamics and kinetics of RNA-protein
      binding is required. This can facilitate the formulation of high-throughput
      screening strategies and the development of structure-activity relationships for
      compound leads. In addition to traditional methods, such as filter binding, gel
      mobility shift assay and various fluorescence techniques, newer methods such as
      surface plasmon resonance and mass spectrometry are being used for the study of
      RNA-protein interactions.

PMID- 10899818
TI  - Microtubule bundling

PMID- 10899817
TI  - Defined media and inert supports: their potential as solid-state fermentation
      production systems.
AB  - Solid-state fermentation (SSF) using inert supports impregnated with chemically
      defined liquid media has several potential applications in both scientific
      studies and in the industrial production of high-value products, such as
      metabolites, biological control agents and enzymes. As a result of its more
      defined system, SSF on inert supports offers numerous advantages, such as
      improved process control and monitoring, and enhanced process consistency,
      compared with cultivation on natural solid substrates.

PMID- 10899819
TI  - Perfecting the craft

PMID- 10899820
TI  - Measure and interpretation of CF gene therapy trial results.

PMID- 10899821
TI  - Interpretation of CF gene therapy trial results

PMID- 10899822
TI  - Gene therapies for the hemophilias.

PMID- 10899823
TI  - HSV-1 amplicon vectors--simplicity and versatility.

PMID- 10899824
TI  - Analysis of muscle creatine kinase regulatory elements in recombinant adenoviral
      vectors.
AB  - Adenoviral gene transfer holds promise for gene therapy, but effective
      transduction of a large and distributed tissue such as muscle will almost
      certainly require systemic delivery. In this context, the use of muscle-specific
      regulatory elements such as the muscle creatine kinase (MCK) promoter and
      enhancer will avoid potentially harmful ectopic expression of transgenes. We
      describe here the development and testing of adenoviral vectors containing small,
      striated muscle-specific, highly active MCK expression cassettes. One of these
      regulatory elements (CK6) is less than 600 bp in length and is 12% as active as
      the CMV promoter/enhancer in muscle. A recombinant adenoviral vector containing
      this regulatory element retains very high muscle specificity, expressing 600-fold
      higher levels of transgene in muscle than in liver. Muscle-specific regulatory
      elements may also increase persistence of transduced muscle cells. Adenoviral
      transduction of dendritic cells has been shown to stimulate cytotoxic T
      lymphocyte (CTL) responses directed against transgene epitopes. We show that
      human dendritic cells infected in vitro with MCK-containing adenoviruses do not
      express significant levels of transgene. Furthermore, while adenoviral vectors
      containing nonspecific promoters are normally cleared from muscle tissue within 1
      month, we show that MCK-containing vectors express significant levels of
      transgene 4 months after intramuscular injection.

PMID- 10899825
TI  - Oligonucleotide scanning of native mRNAs in extracts predicts intracellular
      ribozyme efficiency: ribozyme-mediated reduction of the murine DNA
      methyltransferase.
AB  - Modulation of gene expression by catalytic RNA requires accessible ribozyme
      cleavage sites in the target mRNA, and accessibility is determined by the
      secondary and tertiary structure of the target RNA, as affected by its
      interactions with cellular proteins. As we previously reported, an
      oligonucleotide-scanning approach using antisense oligonucleotides can be used to
      determine RNA accessibility in cell extracts. To test whether this method can be
      used to improve selection of ribozyme target sites, we designed ribozymes
      corresponding to the sites identified by oligonucleotide scanning and have
      evaluated their catalytic activities, first in cell extracts and then in
      transduced cell lines. As a target we used the mRNA of murine DNA (cytosine-5)
      methyltransferase 1 (MTase). For intracellular studies, the ribozyme genes were
      inserted downstream of a Pol III tRNAVAL promoter, which in turn was cloned in
      the U3 region of a retroviral vector. We find that the efficiency of the
      ribozymes both in cell extracts and in vivo corresponds with the relative
      effectiveness predicted by the oligonucleotide-scanning assay. The best ribozyme
      causes a 70-80% reduction in the MTase mRNA levels in NIH 3T3 cells that are
      stably transduced with the retroviral constructs. This reduction in mRNA levels
      is accompanied by a small decrease in the methylation of repetitive
      intercisternal A particle DNA elements. Ribozyme expression also increased
      several-fold the reactivation frequency of a methylation-silenced green
      fluorescent protein (GFP) transgene. Both the reduction in methylation and
      reactivation of GFP were roughly equivalent to the effects obtained by treating
      NIH 3T3 cells with 2.5 microM 5-azacytidine, which gives an effect of about 10%
      of maximum. These results confirm the validity of the cell extract approach for
      ribozyme site selection and provide a potentially useful ribozyme for future
      study of DNA methyltransferase function.

PMID- 10899826
TI  - Rejection of disseminated metastases of colon carcinoma by synergism of IL-12
      gene therapy and 4-1BB costimulation.
AB  - In an orthotopic model of metastatic colon carcinoma established in the liver of
      mice, we have previously shown that the natural killer (NK) cells were the major
      effectors after intratumoral delivery of a recombinant adenovirus expressing the
      murine IL-12 gene. However, tumor cure and long-term survival were achieved only
      in a minority of animals. In the present study, we generated an effective
      antitumoral CD8(+ ) T-cell response by the combination of IL-12 gene therapy and
      systemic delivery of an agonistic monoclonal antibody against 4-1BB, a
      costimulatory molecule expressed on activated T cells. In the IL-12 plus anti-4
      1BB combination treatment, the effective dose of IL-12 could even be reduced even
      up to 18-fold and still achieved a better efficacy than the maximal dose of
      either treatment alone. We further demonstrate that the innate and the adaptive
      antitumoral immune responses were synergistic, as animals bearing hepatic as well
      as multiple pulmonary metastases were quantitatively cured of their diseases
      after IL-12 gene therapy + anti-4-1BB combination treatment. Both NK and CD8(+) T
      cells were necessary in maintaining the long-term antitumor immunity, as
      depletion of either cell type in the cured animals abolished their abilities to
      reject tumor cells implanted at distal sites. These results indicate that
      synergism between innate and adaptive immune responses may be effectively
      exploited to treat patients with metastatic diseases.

PMID- 10899828
TI  - Transduction of feline hematopoietic cells by oncoretroviral vectors pseudotyped
      with the subgroup A feline leukemia virus (FeLV-A).
AB  - The domestic cat is an outbred species with many identified analogues of human
      genetic diseases. Therefore, it has the potential to serve as a large animal
      model for evaluating the feasibility of hematopoietic stem cell gene therapy.
      This study compared gene transfer rates into feline hematopoietic progenitors by
      oncoretroviral vectors pseudotyped with the subgroup A feline leukemia virus
      (FeLV-A), the gibbon ape leukemia virus (GALV), and the murine amphotropic virus.
      Gene transfer rates were superior with the FeLV-A pseudotypes, which were then
      tested for their ability to transduce a cat hematopoietic repopulating cell. At
      more than 1 year posttransplantation, persistent marking was seen in both
      lymphoid and myeloid lineages of a myeloablated domestic cat that had received
      autologous marrow cells transduced with an FeLV-A pseudotyped vector.

PMID- 10899827
TI  - Development of a novel trans-lentiviral vector that affords predictable safety.
AB  - Lentiviral vectors derived from human immunodeficiency virus type 1 (HIV-1) hold
      great promise for gene therapy. However, the possibility of generating
      replication-competent retrovirus (RCR) through genetic recombination raises
      concerns for safety. Here we describe a novel HIV-based packaging system (trans
      lentiviral) that splits gag/gag-pol into two parts: One that expresses gag/gag
      pro and another that expresses reverse transcriptase and integrase as fusion
      partners of viral protein R (Vpr). Using a sensitive assay developed to
      specifically detect recombinant lentiviral DNA mobilization, we demonstrated that
      the trans-lentiviral vector prevents the generation of recombinants that contain
      a functional gag-pol structure, while the lentiviral vector generates env-minus
      recombinant lentivirus that mobilizes recombinant genomes to other cells when
      pseudotyped with an exogenous envelope. Since an intact gag-pol structure is
      absolutely required for retroviral DNA mobilization and RCR, the trans-lentiviral
      vector design significantly reduces this risk. Moreover, it makes it possible to
      assess the risk of RCR and DNA mobilization using an in vitro assay that monitors
      trans-lentiviral vector stocks for the regeneration of the gag-pol structure.
      Therefore, the trans-lentiviral vector design will ensure the greatest
      predictable level of safety for the clinical application of retroviral vectors,
      including HIV-based vectors.

PMID- 10899829
TI  - Enhanced gene expression in mouse lung after PEI-DNA aerosol delivery.
AB  - Aerosol gene delivery to the pulmonary system has vast potential for many
      diseases, including cystic fibrosis and lung cancer. We recently reported that
      polyethyleneimine (PEI), a cationic polymer, holds promise as a gene delivery
      vector for transfection in lung by aerosol. To further optimize the gene
      expression in the lung by aerosol, we utilized 5% CO(2) in air for the
      nebulization of PEI-DNA complexes. Five percent CO(2)-in-air gave a threefold
      higher gene expression compared to normal air using the chloramphenicol acetyl
      transferase (CAT) reporter gene delivered by Aerotech II nebulizer. The delivery
      of DNA by PEI was dose dependent with the highest expression obtained when 2 mg
      of DNA in 10 ml was nebulized at a PEI nitrogen:DNA phosphate (N:P) ratio of
      10:1. The optimal N:P ratio for lung transfection was found to be between 10:1
      and 20:1 using the CAT and luciferase reporter genes. The time-course studies
      showed the highest expression at 24 h after aerosol delivery and 40-50% of peak
      level was detectable even after a week. Tissue distribution indicates the
      expression to be specific to the lung with no detectable expression in any other
      tissue examined. Histological and biochemical analysis of lungs revealed no
      evidence of acute inflammation.

PMID- 10899830
TI  - Critical factors influencing stable transduction of human CD34(+) cells with HIV
      1-derived lentiviral vectors.
AB  - Lentiviral vectors have been proposed as a more efficient alternative to Moloney
      murine leukemia virus-based retroviral vectors for transduction of human
      hematopoietic progenitors and stem cells. These studies were designed to evaluate
      the conditions that influence transduction frequency of CD34(+) progenitors, with
      the goal of optimizing efficiency of stable gene transfer with lentiviral
      vectors. CD34(+) human cord blood cells and 293 cells were transduced with a
      human immunodeficiency virus (HIV)-1 derived lentiviral vector pseudotyped with
      vesicular stomatitis virus glycoprotein and carrying an internal human
      cytomegalovirus promoter driving enhanced green fluorescent protein (eGFP)
      expression. Using fluorescence-activated cell sorting analysis of eGFP, we
      observed pseudotransduction beginning at the time of vector addition and lasting
      up to 24 h in CD34(+) cells and up to 72 h in 293 cells. Integrase-defective
      lentiviral vector caused transient eGFP expression for up to 10 days in CD34(+)
      cells and for up to 14 days in 293 cells. Protamine sulfate conferred no increase
      in transduction efficiency of CD34(+) cells on fibronectin-coated plates.
      Transduction frequency was related directly to vector concentration and not to
      multiplicity of infection across the ranges tested. First- and second-generation
      lentiviral vectors transduced CD34(+) cells equally, demonstrating a lack of
      dependence on HIV-1 accessory proteins. These findings will be useful for the
      optimal utilization of this new class of vectors for transduction of human
      hematopoietic stem cells.

PMID- 10899831
TI  - Significantly increased expression of beta-glucuronidase in the central nervous
      system of mucopolysaccharidosis type VII mice from the latency-associated
      transcript promoter in a nonpathogenic herpes simplex virus type 1 vector.
AB  - Herpes simplex virus (HSV) has the ability to establish life-long latent
      infections in postmitotic neurons and to remain transcriptionally active,
      continuously expressing latency-associated transcripts (LAT) while producing
      minimal disease. These properties have made HSV an excellent candidate for
      neuronal gene transfer. Previously, we have shown that in mucopolysaccharidosis
      type VII mice (MPS VII, beta-glucuronidase deficiency) the LAT promoter is
      capable of expressing beta-glucuronidase (GUSB) in the trigeminal ganglion and
      the brainstem after latency is established. However, the number of neurons
      expressing GUSB is much lower than the number expressing 2-kb LAT following a
      wild-type virus infection. In this study, we have evaluated the effect of the
      position of the coding sequence relative to the LAT promoter on beta
      glucuronidase gene expression in the central nervous system (CNS). Non
      neurovirulent (ICP-34.5-deleted HSV-1) vectors were used, allowing direct
      intracranial injection. Significantly more GUSB activity was detected in brains
      of MPS VII mice inoculated with a recombinant virus (HSV-LAT-GUSB-JS) in which
      the GUSB cDNA was inserted near the LAT promoter, compared to viruses where it
      was inserted farther downstream in either the LAT exon 1 or overlapping exon 1
      and the 2-kb LAT intron. This vector produced more than 100 times the number of
      positive cells than the other constructs. During acute infection, the
      distribution of viral replication differed from the distribution of GUSB enzyme
      expression. Viral antigen was predominately present in cells around the site of
      injection in the caudate putamen and in ependymal cells lining the ventricles. In
      contrast, GUSB expression was present mainly in cells of the thalamus and
      hypothalamus, which did not exhibit viral antigen, suggesting that GUSB enzyme
      activity was expressed from latently but not acutely infected neuronal cells.
      This vector design should be useful for high-level expression of various genes in
      the CNS.

PMID- 10899832
TI  - Metabolic routes as targets for immunological discrimination of host and
      parasite.

PMID- 10899833
TI  - Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via
      carbon dioxide production.
AB  - Helicobacter pylori can produce a persistent infection in the human stomach,
      where chronic and active inflammation, including the infiltration of phagocytes
      such as neutrophils and monocytes, is induced. H. pylori may have a defense
      system against the antimicrobial actions of phagocytes. We studied the defense
      mechanism of H. pylori against host-derived peroxynitrite (ONOO(-)), a
      bactericidal metabolite of nitric oxide, focusing on the role of H. pylori
      urease, which produces CO(2) and NH(3) from urea and is known to be an essential
      factor for colonization. The viability of H. pylori decreased in a time-dependent
      manner with continuous exposure to 1 microM ONOO(-), i.e., 0.2% of the initial
      bacteria remained after a 5-min treatment without urea. The bactericidal action
      of ONOO(-) against H. pylori was significantly attenuated by the addition of 10
      mM urea, the substrate for urease, whereas ONOO(-)-induced killing of a urease
      deficient mutant of H. pylori or Campylobacter jejuni, another microaerophilic
      bacterium lacking urease, was not affected by the addition of urea. Such a
      protective effect of urea was potentiated by supplementation with exogenous
      urease, and it was almost completely nullified by 10 microM flurofamide, a
      specific inhibitor of urease. The bactericidal action of ONOO(-) was also
      suppressed by the addition of 20 mM NaHCO(3) but not by the addition of 20 mM
      NH(3). In addition, the nitration of L-tyrosine of H. pylori after treatment with
      ONOO(-) was significantly reduced by the addition of urea or NaHCO(3), as
      assessed by high-performance liquid chromatography with electrochemical
      detection. These results suggest that H. pylori-associated urease functions to
      produce a potent ONOO(-) scavenger, CO(2)/HCO(3)(-), that defends the bacteria
      from ONOO(-) cytotoxicity. The protective effect of urease may thus facilitate
      sustained bacterial colonization in the infected gastric mucosa.

PMID- 10899834
TI  - Involvement of a plasmid in virulence of Campylobacter jejuni 81-176.
AB  - Campylobacter jejuni strain 81-176 contains two, previously undescribed plasmids,
      each of which is approximately 35 kb in size. Although one of the plasmids,
      termed pTet, carries a tetO gene, conjugative transfer of tetracycline resistance
      to another strain of C. jejuni could not be demonstrated. Partial sequence
      analysis of the second plasmid, pVir, revealed the presence of four open reading
      frames which encode proteins with significant sequence similarity to Helicobacter
      pylori proteins, including one encoded by the cag pathogenicity island. All four
      of these plasmid-encoded proteins show some level of homology to components of
      type IV secretion systems. Mutation of one of these plasmid genes, comB3, reduced
      both adherence to and invasion of INT407 cells to approximately one-third that
      seen with wild-type strain 81-176. Mutation of comB3 also reduced the natural
      transformation frequency. A mutation in a second plasmid gene, a virB11 homolog,
      resulted in a 6-fold reduction in adherence and an 11-fold reduction in invasion
      compared to the wild type. The isogenic virB11 mutant of strain 81-176 also
      demonstrated significantly reduced virulence in the ferret diarrheal disease
      model. The virB11 homolog was detected on plasmids in 6 out of 58 fresh clinical
      isolates of C. jejuni, suggesting that plasmids are involved in the virulence of
      a subset of C. jejuni pathogens.

PMID- 10899836
TI  - Central role of endogenous gamma interferon in protective immunity against blood
      stage Plasmodium chabaudi AS infection.
AB  - The role of endogenous gamma interferon (IFN-gamma) in protective immunity
      against blood-stage Plasmodium chabaudi AS malaria was studied using IFN-gamma
      gene knockout (GKO) and wild-type (WT) C57BL/6 mice. Following infection with
      10(6) parasitized erythrocytes, GKO mice developed significantly higher
      parasitemia during acute infection than WT mice and had severe mortality. In
      infected GKO mice, production of interleukin 12 (IL-12) p70 and tumor necrosis
      factor alpha in vivo and IL-12 p70 in vitro by splenic macrophages was
      significantly reduced compared to that in WT mice and the enhanced nitric oxide
      (NO) production observed in infected WT mice was completely absent. WT and GKO
      mice had comparable numbers of total nucleated spleen cells and B220(+) and Mac
      1(+) spleen cells both before and after infection. Infected WT mice, however, had
      significantly more F4/80(+), NK1.1(+), and F4/80(+)Ia(+) spleen cells than
      infected GKO mice; male WT had more CD3(+) cells than male GKO mice. In
      comparison with those from WT mice, splenocytes from infected GKO mice had
      significantly higher proliferation in vitro in response to parasite antigen or
      concanavalin A stimulation and produced significantly higher levels of IL-10 in
      response to parasite antigen. Infected WT mice produced more parasite-specific
      immunoglobulin M (IgM), IgG2a, and IgG3 and less IgG1 than GKO mice. Significant
      gender differences in both GKO and WT mice in peak parasitemia levels, mortality,
      phenotypes of spleen cells, and proliferation of and cytokine production by
      splenocytes in vitro were apparent during infection. These results thus provide
      unequivocal evidence for the central role of endogenous IFN-gamma in the
      development of protective immunity against blood-stage P. chabaudi AS.

PMID- 10899835
TI  - beta-1,2-linked oligomannosides from Candida albicans bind to a 32-kilodalton
      macrophage membrane protein homologous to the mammalian lectin galectin-3.
AB  - beta-1,2-linked oligomannoside residues are present, associated with mannan and a
      glycolipid, the phospholipomannan, at the Candida albicans cell wall surface.
      beta-1,2-linked oligomannoside residues act as adhesins for macrophages and
      stimulate these cells to undergo cytokine production. To characterize the
      macrophage receptor involved in the recognition of C. albicans beta-1,2
      oligomannoside we used the J774 mouse cell line, which is devoid of the receptor
      specific for alpha-linked mannose residues. A series of experiments based on
      affinity binding on either C. albicans yeast cells or beta-1,2-oligomannoside
      conjugated bovine serum albumin (BSA) and subsequent disclosure with biotinylated
      conjugated BSA repeatedly led to the detection of a 32-kDa macrophage protein. An
      antiserum specific for this 32-kDa protein inhibited C. albicans binding to
      macrophages and was used to immunoprecipitate the molecule. Two high-pressure
      liquid chromatography-purified peptides from the 32-kDa tryptic digest showed
      complete homology to galectin-3 (previously designated Mac-2 antigen), an
      endogenous lectin with pleiotropic functions which is expressed in a wide variety
      of cell types with which C. albicans interacts as a saprophyte or a parasite.

PMID- 10899837
TI  - Identification of a novel gene cluster encoding staphylococcal exotoxin-like
      proteins: characterization of the prototypic gene and its protein product, SET1.
AB  - We report the discovery of a novel genetic locus within Staphylococcus aureus
      that encodes a cluster of at least five exotoxin-like proteins. Designated the
      staphylococcal exotoxin-like genes 1 to 5 (set1 to set5), these open reading
      frames have between 38 and 53% homology to each other. All five proteins contain
      consensus sequences that are found in staphylococcal and streptococcal exotoxins
      and toxic shock syndrome toxin 1 (TSST-1). However, the SETs have only limited
      overall sequence homology to the enterotoxins and TSST-1 and thus represent a
      novel family of exotoxin-like proteins. The prototypic gene in this cluster,
      set1, has been cloned and expressed. Recombinant SET1 stimulated the production
      of interleukin-1beta, interleukin-6, and tumor necrosis factor alpha by human
      peripheral blood mononuclear cells. PCR analysis revealed that set1 was
      distributed among other strains of S. aureus but not in the other staphylococcal
      species examined. Sequence analysis of the set1 genes from different strains
      revealed at least three allelic variants. The protein products of these allelic
      variants displayed a 100-fold difference in their cytokine-inducing potency. The
      distribution of allelic variants of the set genes among strains of S. aureus may
      contribute to differences in the pathogenic potential of this bacterium.

PMID- 10899838
TI  - Protection of gerbils from amebic liver abscess by vaccination with a 25-mer
      peptide derived from the cysteine-rich region of Entamoeba histolytica galactose
      specific adherence lectin.
AB  - The protozoan parasite Entamoeba histolytica causes extensive morbidity and
      mortality through intestinal infection and amebic liver abscess. Here we show
      that immunization of gerbils with a single keyhole limpet hemocyanin-coupled 25
      mer peptide derived from the 170-kDa subunit of the E. histolytica galactose
      binding adhesin is sufficient to confer substantial protection against
      experimentally induced amebic liver abscesses. Vaccination provided total
      protection in 5 of 15 immunized gerbils, and abscesses were significantly smaller
      (P < 0.01) in the remaining vaccinated animals. The degree of protection
      correlated with the titer of antibodies to the peptide, and results of passive
      transfer experiments performed with SCID mice were consistent with a role for
      antibodies in protection. In addition, parenteral or oral vaccination of gerbils
      with 13-amino-acid subfragments of the peptide N-terminally fused to the B
      subunit of cholera toxin also significantly inhibited liver abscess formation (P
      < 0.05). These data indicate that small peptides derived from the galactose
      binding adhesin administered by the parenteral or oral route can provide
      protection against amebic liver abscess and should be considered as components of
      a subunit vaccine against invasive amoebiasis.

PMID- 10899839
TI  - Differential tumor necrosis factor alpha expression and release from peritoneal
      mouse macrophages in vitro in response to proliferating gram-positive versus gram
      negative bacteria.
AB  - Viable Escherichia coli and Staphylococcus aureus bacteria elicited markedly
      different in vitro tumor necrosis factor alpha (TNF-alpha) responses when placed
      in coculture with peritoneal murine macrophages. These include quantitative
      differences in TNF-alpha mRNA expression and corresponding protein product
      secretion as well as kinetic differences in the profiles of the TNF-alpha
      responses. Further, lipopolysaccharide (from E. coli) is a major contributing
      factor to these differences, as revealed by comparative experiments with
      endotoxin-responsive (C3Heb/FeJ) and endotoxin-hyporesponsive (C3H/HeJ)
      macrophages. Nevertheless, the eventual overall magnitude of the TNF-alpha
      secretion of macrophages in response to S. aureus was at least equivalent to that
      observed with E. coli, while appearing at time periods hours later than the E.
      coli-elicited TNF-alpha response. Both the magnitude and kinetic profile of the
      TNF-alpha responses were found to be relatively independent of the rate of
      bacterial proliferation, at least to the extent that similar results were
      observed with both viable and paraformaldehyde-killed microbes. Nevertheless, S.
      aureus treated in culture with the carbapenem antibiotic imipenem manifests
      markedly altered profiles of TNF-alpha response, with the appearance of an early
      TNF-alpha peak not seen with viable organisms, a finding strikingly similar to
      that recently reported by our laboratory from in vivo studies (R. Silverstein, J.
      G. Wood, Q. Xue, M. Norimatsu, D. L. Horn, and D. C. Morrison, Infect. Immun.
      68:2301-2308, 2000). In contrast, imipenem treatment of E. coli-cocultured
      macrophages does not significantly alter the observed TNF-alpha response either
      in vitro or in vivo. In conclusion, our data support the concept that the host
      inflammatory response of cultured mouse macrophages in response to viable gram
      positive versus gram-negative microbes exhibits distinctive characteristics and
      that these distinctions are, under some conditions, altered on subsequent
      bacterial killing, depending on the mode of killing. Of potential importance,
      these distinctive in vitro TNF-alpha profiles faithfully reflect circulating
      levels of TNF-alpha in infected mice. These results suggest that coculture of
      peritoneal macrophages with viable versus antibiotic-killed bacteria and
      subsequent assessment of cytokine response (TNF-alpha) may be of value in
      clarifying, and ultimately controlling, related host inflammatory responses in
      septic patients.

PMID- 10899841
TI  - Genetic characterization of a Streptococcus mutans LraI family operon and role in
      virulence.
AB  - Proteins belonging to the LraI (for "lipoprotein receptor antigen") family
      function as adhesins in several streptococci, as a virulence factor for
      endocarditis in at least one of these species, and potentially as metal
      transporters in many bacteria. We have identified and characterized the
      chromosomal locus containing the LraI family gene (designated sloC) from
      Streptococcus mutans, an agent of dental caries and endocarditis in humans.
      Northern blot analysis indicated that sloC is cotranscribed with three other
      genes. As with other LraI operons, the sloA and sloB genes apparently encode
      components of an ATP-binding cassette transport system. The product of the fourth
      gene, sloR, has homology to the metal-dependent regulator from Corynebacterium
      diphtheriae, DtxR. A potential binding site for SloR was identified upstream from
      the sloABCR operon and was conserved upstream from LraI operons in several other
      streptococci. Potential SloR homologs were identified in the unfinished genomic
      sequences from two of these, S. pneumoniae and S. pyogenes. Mutagenesis of sloC
      in S. mutans resulted in apparent loss of expression of the entire operon as
      assessed by Northern blot analysis. The sloC mutant was indistinguishable from
      its wild-type parent in a gnotobiotic rat model of caries but was significantly
      less virulent in a rat model of endocarditis. Virulence for endocarditis was
      restored by correction of the sloC mutation but not by provision of the sloC gene
      in trans, suggesting that virulence requires the expression of other genes in the
      sloC operon.

PMID- 10899840
TI  - Induction of proinflammatory cytokines from human respiratory epithelial cells
      after stimulation by nontypeable Haemophilus influenzae.
AB  - Nontypeable Haemophilus influenzae (NTHi) causes repeated respiratory infections
      in patients with chronic lung diseases. These infections are characterized by a
      brisk inflammatory response which results in the accumulation of
      polymorphonucleated cells in the lungs and is dependent on the expression and
      secretion of proinflammatory cytokines. We hypothesize that multiple NTHi
      molecules, including lipooligosaccharide (LOS), mediate cellular interactions
      with respiratory epithelial cells, leading to the production of proinflammatory
      cytokines. To address this hypothesis, we exposed 9HTEo- human tracheal
      epithelial cells to NTHi and compared the resulting profiles of cytokine gene
      expression and secretion using multiprobe RNase protection assays and enzyme
      linked immunosorbent assays (ELISA), respectively. Dose-response experiments
      demonstrated a maximum stimulation of most cytokines tested, using a ratio of 100
      NTHi bacterial cells to 1 9HTEo- tracheal epithelial cell. Compared with purified
      LOS, NTHi bacterial cells stimulated 3.6- and 4.5-fold increases in epithelial
      cell expression of interleukin-8 (IL-8) and IL-6 genes, respectively. Similar
      results were seen with epithelial cell macrophage chemotactic protein 1, IL
      1alpha, IL-1beta, and tumor necrosis factor alpha expression. Polymyxin B
      completely inhibited LOS stimulation but only partially reduced NTHi whole cell
      stimulation. Taken together, these results suggest that multiple bacterial
      molecules including LOS contribute to the NTHi stimulation of respiratory
      epithelial cell cytokine production. Moreover, no correlation was seen between
      NTHi adherence to epithelial cells mediated by hemagglutinating pili, Hia, HMW1,
      HMW2, and Hap and epithelial cytokine secretion. These data suggest that
      bacterial molecules beyond previously described NTHi cell surface adhesins and
      LOS play a role in the induction of proinflammatory cytokines from respiratory
      epithelial cells.

PMID- 10899843
TI  - Antiviral activity of shiga toxin 1: suppression of bovine leukemia virus-related
      spontaneous lymphocyte proliferation.
AB  - Human infections with Shiga toxin (Stx)-producing Escherichia coli (STEC) cause
      hemorrhagic colitis. The Stxs belong to a large family of ribosome-inactivating
      proteins (RIPs) that are found in a variety of higher plants and some bacteria.
      Many RIPs have potent antiviral activity for the plants that synthesize them.
      STEC strains, both virulent and nonvirulent to humans, are frequently isolated
      from healthy cattle. Interestingly, despite intensive investigations, it is not
      known why cattle carry STEC. We tested the hypothesis that Stx has antiviral
      properties for bovine viruses by assessing the impact of Stx type 1 (Stx1) on
      bovine peripheral blood mononuclear cells (PBMC) from cows infected with bovine
      leukemia virus (BLV). PBMC from BLV-positive animals invariably displayed
      spontaneous lymphocyte proliferation (SLP) in vitro. Stx1 or the toxin A subunit
      (Stx1A) strongly inhibited SLP. Toxin only weakly reduced the pokeweed mitogen-
      or interleukin-2-induced proliferation of PBMC from normal (BLV-negative) cows
      and had no effect on concanavalin A-induced proliferation. The toxin activity in
      PBMC from BLV-positive cattle was selective for viral SLP and did not abrogate
      cell response to pokeweed mitogen- or interleukin-2-induced proliferation.
      Antibody to virus or Stx1A was most effective at inhibiting SLP if administered
      at the start of cell culture, indicating that both reagents likely interfere with
      BLV-dependent initiation of SLP. Stx1A inhibited expression of BLV p24 protein by
      PBMC. A well-defined mutant Stx1A (E167D) that has decreased catalytic activity
      was not effective at inhibiting SLP, suggesting the inhibition of protein
      synthesis is likely the mechanism of toxin antiviral activity. Our data suggest
      that Stx has potent antiviral activity and may serve an important role in BLV
      infected cattle by inhibiting BLV replication and thus slowing the progression of
      infection to its malignant end stage.

PMID- 10899842
TI  - Yersinia pestis YbtU and YbtT are involved in synthesis of the siderophore
      yersiniabactin but have different effects on regulation.
AB  - One prerequisite for the virulence of Yersinia pestis, causative agent of bubonic
      plague, is the yersiniabactin (Ybt) siderophore-dependent iron transport system
      that is encoded within a high-pathogenicity island (HPI) within the pgm locus of
      the Y. pestis chromosome. Several gene products within the HPI have demonstrated
      functions in the synthesis or transport of Ybt. Here we examine the roles of ybtU
      and ybtT. In-frame mutations in ybtT or ybtU yielded strains defective in
      siderophore production. Mutant strains were unable to grow on iron-deficient
      media at 37 degrees C but could be cross-fed by culture supernatants from a Ybt
      producing strain of Y. pestis. The ybtU mutant failed to express four indicator
      Ybt proteins (HMWP1, HMWP2, YbtE, and Psn), a pattern similar to those for other
      ybt biosynthetic mutants. In contrast, strains carrying mutations in ybtT or ybtS
      (a previously identified gene required for Ybt biosynthesis) produced all four
      proteins at wild-type levels under iron-deprived conditions. To assess the
      effects of ybtT, -U, and -S mutations on transcription of ybt genes, reporter
      plasmids with ybtP or psn promoters controlling lacZ expression were introduced
      into these mutants. Normal iron-regulated beta-galactosidase activity was
      observed in the ybtT and ybtS mutants, whereas a significant loss of expression
      occurred in the DeltaybtU strain. These results show that ybtT and ybtU genes are
      involved in the biosynthesis of the Ybt siderophore and that a ybtU mutation but
      not ybtT or ybtS mutations affects transcription from the ybtP and psn promoters.

PMID- 10899844
TI  - Adaptive immunity against Listeria monocytogenes in the absence of type I tumor
      necrosis factor receptor p55.
AB  - Tumor necrosis factor (TNF) and the type I TNF receptor (TNFRI), p55, are
      critical for resistance against primary infections with the intracellular
      bacterial pathogen Listeria monocytogenes. Importantly, however, susceptibility
      to primary listeriosis in cytokine-deficient mice does not preclude the
      development or expression of effective adaptive immunity against virulent L.
      monocytogenes. We used TNFRI(-/-) mice to study adaptive antilisterial immunity
      in the absence of interactions between TNF and TNFRI. Our experiments indicate
      that TNFRI(-/-) mice survive and clear high-dose challenges with an attenuated
      strain of L. monocytogenes that is incapable of cell-to-cell spread. Furthermore,
      TNFRI(-/-) mice immunized with attenuated L. monocytogenes go on to develop
      potent adaptive immunity to subsequent high-dose challenges with virulent L.
      monocytogenes. Interestingly, CD8(+) T-cell depletion in vivo inhibits immunity
      to L. monocytogenes in the spleen but not in the liver of TNFRI(-/-) mice. The
      adaptive immune response in these animals is characterized by activation of
      listeriolysin O-specific CD8(+) T cells, which are capable of transferring
      antilisterial immunity to naive wild-type C57BL/6 host mice. These experiments
      demonstrate the development and expression of potent CD8(+) T-cell-mediated
      antilisterial immunity in the absence of TNFRI.

PMID- 10899845
TI  - Depressed interleukin-12 (IL-12), but not IL-18, production in response to a 30-
      or 32-kilodalton mycobacterial antigen in patients with active pulmonary
      tuberculosis.
AB  - The secreted 30-kDa antigen (Ag) of Mycobacterium tuberculosis directly
      stimulates Th1-type protective cytokine responses in healthy tuberculin reactors
      but not in patients with active tuberculosis (TB). To examine the cytokine
      profiles attributable to Th1 suppression associated with active TB, interleukin
      12 (IL-12), IL-18, and IL-10 production in response to a 30- or 32-kDa Ag in 16
      patients with active pulmonary TB and 24 healthy controls was investigated by
      enzyme-linked immunosorbent assay. In TB patients, production of IL-12 p40, as
      well as gamma interferon (IFN-gamma), by 30- or 32-kDa Ag-stimulated peripheral
      blood mononuclear cells (PBMC) was significantly decreased compared with that in
      healthy tuberculin reactors. There were no significant differences in IL-18
      production between patients and controls early during stimulation (16 h).
      However, PBMC from patients showed significantly enhanced IL-18 proteins after 96
      h of stimulation. Similarly, higher IL-10 production was observed in the TB
      patients than in healthy tuberculin reactors. After 2 months of anti-TB therapy,
      the mean IFN-gamma and IL-12 p40 production and the mean blastogenic responses
      were significantly increased in PBMC in the 10 TB patients who were followed up.
      Our findings provide evidence that depressed IL-12 in response to the 30- or 32
      kDa Ag is involved in the immunopathogenesis of human active pulmonary TB.

PMID- 10899846
TI  - Salmonella enterica serovar typhimurium waaP mutants show increased
      susceptibility to polymyxin and loss of virulence In vivo.
AB  - In Escherichia coli, the waaP (rfaP) gene product was recently shown to be
      responsible for phosphorylation of the first heptose residue of the
      lipopolysaccharide (LPS) inner core region. WaaP was also shown to be necessary
      for the formation of a stable outer membrane. These earlier studies were
      performed with an avirulent rough strain of E. coli (to facilitate the structural
      chemistry required to properly define waaP function); therefore, we undertook the
      creation of a waaP mutant of Salmonella enterica serovar Typhimurium to assess
      the contribution of WaaP and LPS core phosphorylation to the biology of an
      intracellular pathogen. The S. enterica waaP mutant described here is the first
      to be both genetically and structurally characterized, and its creation refutes
      an earlier claim that waaP mutations in S. enterica must be leaky to maintain
      viability. The mutant was shown to exhibit characteristics of the deep-rough
      phenotype, despite its ability to produce a full-length core capped with O
      antigen. Further, phosphoryl modifications in the LPS core region were shown to
      be required for resistance to polycationic antimicrobials. The waaP mutant was
      significantly more sensitive to polymyxin in both wild-type and polymyxin
      resistant backgrounds, despite the decreased negative charge of the mutant LPSs.
      In addition, the waaP mutation was shown to cause a complete loss of virulence in
      mouse infection models. Taken together, these data indicate that WaaP is a
      potential target for the development of novel therapeutic agents.

PMID- 10899847
TI  - Safety and immunogenicity of two different lots of the oral, killed
      enterotoxigenic escherichia coli-cholera toxin B subunit vaccine in Israeli young
      adults.
AB  - Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of diarrhea
      among Israeli soldiers serving in field units. Two double-blind placebo
      controlled, randomized trials were performed among 155 healthy volunteers to
      evaluate the safety and immunogenicity of different lots of the oral, killed ETEC
      vaccine consisting of two doses of whole cells plus recombinantly produced
      cholera toxin B subunit (rCTB). The two doses of vaccine lot E005 and the first
      dose of vaccine lot E003 were well tolerated by the volunteers. However, 5 (17%)
      vaccinees reported an episode of vomiting a few hours after the second dose of
      lot E003; none of the placebo recipients reported similar symptoms. Both lots of
      vaccine stimulated a rate of significant antibody-secreting cell (ASC) response
      to CTB and to colonization factor antigen I (CFA/I) after one or two doses,
      ranging from 85 to 100% and from 81 to 100%, respectively. The rate of ASC
      response to CS2, CS4, and CS5 was slightly lower than the rate of ASC response
      induced to CTB, CFA/I, and CS1. The second vaccine dose enhanced the response to
      CTB but did not increase the frequencies or magnitude of ASC responses to the
      other antigens. The two lots of the ETEC vaccine induced similar rates of serum
      antibody responses to CTB and CFA/I which were less frequent than the ASC
      responses to the same antigens. Based on these safety and immunogenicity data, an
      efficacy study of the ETEC vaccine is under way in the Israel Defense Force.

PMID- 10899848
TI  - Requirement of the Pseudomonas aeruginosa tonB gene for high-affinity iron
      acquisition and infection.
AB  - To investigate the contribution of the TonB protein to high-affinity iron
      acquisition in Pseudomonas aeruginosa, we constructed tonB-inactivated mutants
      from strain PAO1 and its derivative deficient in producing the siderophores
      pyoverdin and pyochelin. The tonB mutants could not grow in a free-iron
      restricted medium prepared by apotransferrin addition, even though the medium was
      supplemented with each purified siderophore or with a heme source (hemoglobin or
      hemin). The tonB inactivation was shown to make P. aeruginosa unable to acquire
      iron from the transferrin with either siderophore. Introduction of a plasmid
      carrying the intact tonB gene restored growth of the tonB mutant of PAO1 in the
      free-iron-restricted medium without any supplements and restored growth of the
      tonB mutant of the siderophore-deficient derivative in the medium supplemented
      with pyoverdin, pyochelin, hemoglobin, or hemin. In addition, animal experiments
      showed that, in contrast to PAO1, the tonB mutant of PAO1 could not grow in vivo,
      such as in the muscles and lungs of immunosuppressed mice, and could not kill any
      of the animals. The in vivo growth ability and lethal virulence were also
      restored by introduction of the tonB-carrying plasmid in the tonB mutant. These
      results indicate clearly that the intact tonB gene-and, therefore, the TonB
      protein encoded by it-is essential for iron acquisition mediated by pyoverdin and
      pyochelin and via heme uptake in P. aeruginosa and suggest that the TonB
      dependent iron acquisition may be essential for P. aeruginosa to infect the
      animal host.

PMID- 10899849
TI  - Variability of outer membrane protein P1 and its evaluation as a vaccine
      candidate against experimental otitis media due to nontypeable Haemophilus
      influenzae: an unambiguous, multifaceted approach.
AB  - Candidate vaccine antigens for preventing otitis media caused by nontypeable
      Haemophilus influenzae (NTHI) should possess one or more conserved epitopes. We
      sought to evaluate the candidacy of P1, a surface-expressed outer membrane
      protein knowing that this antigen is subject to diversifying selection.
      Therefore, we selected NTHI strains from among >500 phylogenically variant
      isolates representative of the diversity found in natural populations of H.
      influenzae. Twenty-three variants of P1 (</=95% similarity) were identified among
      42 strains. When chinchillas were immunized with recombinant P1 (rP1) obtained
      from one of these isolates (BCH-3), all animals developed antibodies specific for
      rP1. Immunized animals were protected against disease when challenged with BCH-3,
      but not with an ompP1 mutant of BCH-3 or a strain (BCH-2) possessing a
      heterologous P1 (91% identity). We conclude that (i) while P1 induces protection
      against NTHI-mediated otitis media, development of a polyvalent vaccine
      reflecting the variability of P1 would be necessary to construct an efficacious
      vaccine and (ii) use of a phylogenically characterized collection of
      representative isolates in concert with gene sequencing, cloning, gene
      inactivation, and animal testing offers an efficient, rational, and rigorous
      strategy for evaluating the potential problems associated with variability of
      vaccine targets and specificity of related immune responses.

PMID- 10899850
TI  - Growth of Mycobacterium tuberculosis in a defined medium is very restricted by
      acid pH and Mg(2+) levels.
AB  - Mycobacterium tuberculosis grows within the phagocytic vacuoles of macrophages,
      where it encounters a moderately acidic and possibly nutrient-restricted
      environment. Other mycobacterial species encounter acidic conditions in soil and
      aquatic environments. We have evaluated the influence of pH and divalent cation
      levels on the growth of M. tuberculosis and seven other mycobacterial species. In
      a defined medium, the growth of M. tuberculosis was very restricted by acidic pH.
      Higher levels of Mg(2+) were required for growth of M. tuberculosis in mildly
      acidic media (pH 6.0 to 6.5) compared to pH 7. 0 medium. The divalent cations
      Ca(2+), Zn(2+), or Mn(2+) could not replace Mg(2+) during growth at pH 6.25, but
      Ca(2+) could at least partially substitute for Mg(2+) during growth at pH 7.0.
      Among eight species of mycobacteria tested, there was a diversity of growth rates
      in media with acidic pH and low Mg(2+) levels. M. tuberculosis was the most
      restricted in growth at pH 6.0, and all of this growth required elevated levels
      of Mg(2+). M. kansasii and M. smegmatis also grew very poorly in acidic media
      with limiting Mg(2+). M. fortuitum, M. marinum, M. scrofulaceum, M. avium, and M.
      chelonae grew at pH 6.0 in an unrestricted manner. These results demonstrate that
      M. tuberculosis is unique among the mycobacteria in its extreme sensitivity to
      acid and indicate that M. tuberculosis must acquire sufficient Mg(2+) in order to
      grow in a mildly acidic environment such as within the phagosome of macrophages.

PMID- 10899851
TI  - Invasion of epithelial cells by Yersinia pestis: evidence for a Y. pestis
      specific invasin.
AB  - The causative agent of plague, Yersinia pestis, is regarded as being noninvasive
      for epithelial cells and lacks the major adhesins and invasins of its
      enteropathogenic relatives Yersinia enterocolitica and Yersinia
      pseudotuberculosis. However, there are studies indicating that Y. pestis invades
      and causes systemic infection from ingestive and aerogenic routes of infection.
      Accordingly, we developed a gentamicin protection assay and reexamined
      invasiveness of Y. pestis for HeLa cells. By optimizing this assay, we discovered
      that Y. pestis is highly invasive. Several factors, including the presence of
      fetal bovine serum, the configuration of the tissue culture plate, the
      temperature at which the bacteria are grown, and the presence of the plasminogen
      activator protease Pla-encoding plasmid pPCP1, were found to influence
      invasiveness strongly. Suboptimal combinations of these factors may have
      contributed to negative findings by previous studies attempting to demonstrate
      invasion by Y. pestis. Invasion of HeLa cells was strongly inhibited by
      cytochalasin D and modestly inhibited by colchicine, indicating strong and modest
      respective requirements for microfilaments and microtubules. We found no
      significant effect of the iron status of yersiniae or of the pigmentation locus
      on invasion and likewise no significant effect of the Yops regulon. However, an
      unidentified thermally induced property (possibly the Y. pestis-specific capsular
      protein Caf1) did inhibit invasiveness significantly, and the plasmid pPCP1,
      unique to Y. pestis, was essential for highly efficient invasion. pPCP1 encodes
      an invasion-promoting factor and not just an adhesin, because Y. pestis lacking
      this plasmid still adhered to HeLa cells. These studies have enlarged our picture
      of Y. pestis biology and revealed the importance of properties that are unique to
      Y. pestis.

PMID- 10899852
TI  - Differential modulation and subsequent blockade of mitogenic signaling and cell
      cycle progression by Pasteurella multocida toxin.
AB  - The intracellularly acting protein toxin of Pasteurella multocida (PMT) causes
      numerous effects in cells, including activation of inositol 1,4,5-trisphosphate
      (IP(3)) signaling, Ca(2+) mobilization, protein phosphorylation, morphological
      changes, and DNA synthesis. The direct intracellular target of PMT responsible
      for activation of the IP(3) pathway is the G(q/11)alpha-protein, which stimulates
      phospholipase C (PLC) beta1. The relationship between PMT-mediated activation of
      the G(q/11)-PLC-IP(3) pathway and its ability to promote mitogenesis and cellular
      proliferation is not clear. PMT stimulation of p42/p44 mitogen-activated protein
      kinase occurs upstream via G(q/11)-dependent transactivation of the epidermal
      growth factor receptor. We have further characterized the effects of PMT on the
      downstream mitogenic response and cell cycle progression in Swiss 3T3 and Vero
      cells. PMT treatment caused dramatic morphological changes in both cell lines. In
      Vero cells, limited multinucleation, nuclear fragmentation, and disruption of
      cytokinesis were also observed; however, a strong mitogenic response occurred
      only with Swiss 3T3 cells. Significantly, this mitogenic response was not
      sustained. Cell cycle analysis revealed that after the initial mitogenic response
      to PMT, both cell types subsequently arrested primarily in G(1) and became
      unresponsive to further PMT treatment. In Swiss 3T3 cells, PMT induced up
      regulation of c-Myc; cyclins D1, D2, D3, and E; p21; PCNA; and the Rb proteins,
      p107 and p130. In Vero cells, PMT failed to up-regulate PCNA and cyclins D3 and
      E. We also found that the initial PMT-mediated up-regulation of several of these
      signaling proteins was not sustained, supporting the subsequent cell cycle
      arrest. The consequences of PMT entry thus depend on the differential regulation
      of signaling pathways within different cell types.

PMID- 10899853
TI  - Characterization of a multigene family undergoing high-frequency DNA
      rearrangements and coding for abundant variable surface proteins in Mycoplasma
      agalactiae.
AB  - A family of abundant surface proteins (Vpmas [variable proteins of Mycoplasma
      agalactiae]) undergoing phase variation in M. agalactiae has been characterized
      using monoclonal antibodies and specific polyclonal sera. Two expressed members
      of 39 kDa (Vpma39) and 34 kDa (Vpma34), which varied in expression between clones
      of a lineage, shared a common amino-terminal sequence but were immunologically
      distinct. An amino-terminal oligonucleotide probe identified multiple vpma genes
      which were clustered within a 14-kb ClaI genomic fragment. Rearrangements were
      found to have occurred within the vpma locus between clones which correlated with
      changes in their Vpma phenotype. Two neighboring vpma genes were cloned and
      sequenced from one M. agalactiae clonal variant expressing Vpma39. The two genes,
      vpmaX and vpmaY, were orientated divergently and shared highly homologous 5'
      untranslated regions, 25-amino-acid (aa) lipoprotein leader sequences, and amino
      terminal sequences. The vpmaY gene coded for 346 aa and 84% of the open reading
      frame, comprised of 1.5 units of a large repeat of 186 aa. Although the sequence
      for an entire second vpmaY repeat was present, it was prematurely terminated by
      insertion of two nucleotides. The vpmaX gene encoded 221 aa and possessed 102 aa
      of the 186-aa repeat of vpmaY. Many of the features in common between the vpma
      genes were also found to be shared by the vsp genes of M. bovis, which also
      undergo DNA rearrangements concomitant with phenotypic changes. Since M. bovis is
      the closest phylogenetic relative to M. agalactiae, the vpma and vsp gene
      families most probably represent homologous systems.

PMID- 10899854
TI  - Attenuated nontoxinogenic and nonencapsulated recombinant Bacillus anthracis
      spore vaccines protect against anthrax.
AB  - Several highly attenuated spore-forming nontoxinogenic and nonencapsulated
      Bacillus anthracis vaccines differing in levels of expression of recombinant
      protective antigen (rPA) were constructed. Biochemical analyses (including
      electrospray mass spectroscopy and N terminus amino acid sequencing) as well as
      biological and immunological tests demonstrated that the rPA retains the
      characteristics of native PA. A single immunization of guinea pigs with 5 x 10(7)
      spores of one of these recombinant strains, MASC-10, expressing high levels of
      rPA (>/=100 microgram/ml) from a constitutive heterologous promoter induced high
      titers of neutralizing anti-PA antibodies. This immune response was long lasting
      (at least 12 months) and provided protection against a lethal challenge of
      virulent (Vollum) anthrax spores. The recombinant B. anthracis spore vaccine
      appears to be more efficacious than the vegetative cell vaccine. Furthermore,
      while results clearly suggest a direct correlation between the level of
      expression of PA and the potency of the vaccine, they also suggest that some B.
      anthracis spore-associated antigen(s) may contribute in a significant manner to
      protective immunity.

PMID- 10899855
TI  - Cloning and DNA sequence analysis of an immunogenic glucose-galactose MglB
      lipoprotein homologue from Brachyspira pilosicoli, the agent of colonic
      spirochetosis.
AB  - Colonic spirochetosis (CS) is a newly emerging infectious disease of humans and
      animals caused by the pathogenic spirochete Brachyspira (formerly Serpulina)
      pilosicoli. The purpose of this study was to characterize an antigen that was
      recognized by antibodies present in sera of challenge-exposed pigs. The gene
      encoding the antigen was identified by screening a plasmid library of human B.
      pilosicoli strain SP16 (ATCC 49776) genomic DNA with hyperimmune and convalescent
      swine sera. The predicted amino acid sequence encoded by the cloned B. pilosicoli
      gene had a high degree of similarity and identity to glucose-galactose MglB
      lipoprotein. Located 106 bp downstream of the putative mglB gene was a 3'
      truncated open reading frame with 73.8% similarity and 66.3% identity to mglA of
      Escherichia coli, suggesting a gene arrangement within an operon which is similar
      to those of other bacteria. A single copy of the gene was present in B.
      pilosicoli, and homologous sequences were widely conserved among porcine
      intestinal spirochetes Serpulina intermedia, Brachyspira innocens, Brachyspira
      murdochii, and the avian Brachyspira alvinipulli, but not in porcine Brachyspira
      hyodysenteriae, human Brachyspira aalborgi, and porcine Treponema succinifaciens.
      The deduced molecular weight of the mature MglB lipoprotein was consistent with
      expression by the cloned gene of a polypeptide with an apparent molecular weight
      of 36,000, as determined by Western blot analysis and [(3)H]palmitate labeling.
      Because mucin is the principal constituent of the colonic mucus gel and consists
      of glycoproteins that can serve as the substrate for growth and chemotaxis of B.
      pilosicoli in vitro, a role for MglB in mucosal localization of the spirochete
      appears consistent with the pathogenesis of CS. However, the presence of
      homologous sequences in closely related but nonpathogenic commensal spirochetes
      suggests that other virulence determinants may be required for pathogenesis.

PMID- 10899856
TI  - The C terminus of component C2II of Clostridium botulinum C2 toxin is essential
      for receptor binding.
AB  - The binary Clostridium botulinum C2 toxin consists of two separate proteins, the
      binding component C2II (80.5 kDa) and the actin-ADP-ribosylating enzyme component
      C2I (49.4 kDa). For its cytotoxic action, C2II binds to a cell membrane receptor
      and induces cell entry of C2I via receptor-mediated endocytosis. Here we studied
      the structure-function relationship of C2II by constructing truncated C2II
      proteins and producing polyclonal antisera against selective regions of C2II. An
      antibody raised against the C terminus (amino acids 592 to 721) of C2II inhibited
      binding of C2II to cells. The antibody prevented pore formation by C2II oligomers
      in artificial membranes but did not influence the properties of existing
      channels. To further define the region responsible for receptor binding, we
      constructed proteins with deletions in C2II; specifically, they lacked amino acid
      residues 592 to 721 and the 7 C-terminal amino acid residues. The truncated
      proteins still formed sodium dodecyl sulfate-stable oligomers but were unable to
      bind to cells. Our data indicate that the C terminus of C2II mediates binding of
      the protein to cells and that the 7 C-terminal amino acids are structurally
      important for receptor binding.

PMID- 10899857
TI  - CD4(+) cells are indispensable for ulcer development in murine cutaneous
      leishmaniasis.
AB  - One of the most characteristic clinical features in cutaneous leishmaniasis is
      the development of nodules followed by ulcerations at the site of infection.
      Leishmania amazonensis-infected mice show similar ulcerative lesions. Leishmania
      infected severe combined immunodeficiency (SCID) mice, however, have been shown
      to develop nonulcerative nodules. In the present study, the roles of T cells in
      ulceration were examined using SCID mice in cell reconstitution experiments.
      After development of nonulcerative nodules, SCID mice were inoculated with
      splenocytes from either Leishmania-infected or naive immunocompetent mice,
      resulting in ulceration in all mice. When naive splenocytes were depleted of
      CD4(+), CD8(+), or B220(+) cell populations and the remaining cells were injected
      into Leishmania-infected SCID mice after the development of nodules, only SCID
      mice inoculated with splenocytes depleted of CD4(+) cells did not show
      ulceration. The evidence obtained in this study clearly shows that the CD4(+)
      cell population is indispensable for ulceration in leishmaniasis lesions of SCID
      mice.

PMID- 10899858
TI  - Macrophage damage by Leishmania amazonensis cytolysin: evidence of pore formation
      on cell membrane.
AB  - We have previously shown that both promastigotes and amastigotes of Leishmania
      amazonensis contain a lytic protein that damages erythrocytes and nucleated
      cells, including macrophages (F. S. M. Noronha, F. J. Ramalho-Pinto, and M. F.
      Horta, Infect. Immun. 64:3975-3982, 1996). Using the patch-clamp technique, we
      show here that cell damage by parasite extracts is mediated by the formation of
      nonselective pores on the target membrane. This demonstrates that L. amazonensis
      cytolysin is a pore-forming protein (PFP), here named leishporin. We show that
      the diameters of the pores formed by parasite extracts are heterogeneous, varying
      from approximately 1.6 to >6.1 nm according to cytolysin concentration or time.
      We also show that pore formation involves the binding of the PFP to the target
      cell membrane, a temperature-independent event that is necessary but not
      sufficient to lyse cells. This is followed by a temperature-dependent step that
      triggers lysis, probably the insertion and the polymerization of protein subunits
      in the lipid bilayer. We provide evidence that suggests that polymerization of
      single subunits must occur for pore formation. We show, in addition, that L.
      amazonensis expresses molecules antigenically homologous to other PFPs.

PMID- 10899859
TI  - Role of pulmonary alveolar macrophages in defense of the lung against Pseudomonas
      aeruginosa.
AB  - Alveolar macrophages (AM) provide one of the first lines of defense against
      microbial invasion in the lower airways. The role of AM in the clearance of
      Pseudomonas aeruginosa in mice after intrapulmonary challenge was evaluated. AM
      were depleted by intranasal administration of liposome-encapsulated
      dichloromethylene diphosphonate. At 24 h following the instillation of liposomes,
      a sublethal dose of P. aeruginosa was inoculated intranasally. Spleen, liver, and
      lung tissue was then evaluated for viable bacteria and for histopathology. AM
      depletion of 78 to 88% did not affect the survival rate of infected mice or
      clearance of P. aeruginosa from the spleen, liver, or lung, compared to the
      control group, but the mice's susceptibility to Klebsiella pneumoniae was greatly
      enhanced. The recruitment of neutrophils to the lung was also not affected.
      Freshly explanted AM were not competent to phagocytose unopsonized P. aeruginosa
      but were able to phagocytose zymosan particles. Further studies were conducted to
      assess the in situ phagocytic activities of AM. Three hours after the intranasal
      instillation of P. aeruginosa or other particles, bronchoalveolar lavage was
      performed. AM phagocytosis of zymosan particles and latex beads exceeded that of
      P. aeruginosa. Neutrophils were recruited to the lung in response to a high-dose
      bacterial challenge. These results suggest that AM do not play an important role
      in defense of the lung against P. aeruginosa.

PMID- 10899860
TI  - Evaluation of phase variation of nontypeable Haemophilus influenzae
      lipooligosaccharide during nasopharyngeal colonization and development of otitis
      media in the chinchilla model.
AB  - Nontypeable Haemophilus influenzae (NTHI) has four loci, lic-1 to lic-3 and lgtC,
      that generate phase-variable lipooligosaccharide (LOS) structures. lic-1, which
      is required for the expression of phosphorylcholine (ChoP), is the best
      characterized and is associated with an enhanced ability of H. influenzae to
      persist within the nasopharynges of infant rats. Recent data indicate that LOS
      impacts various aspects of NTHI virulence in the chinchilla model of
      nasopharyngeal colonization and otitis media (OM). In this study the effects of
      ChoP expression and the sequences of lic-1 to lic-3 and lgtC of NTHI strain 2019
      were evaluated in the chinchilla OM model. Nasopharyngeal colonization data
      showed that a switch from the ChoP(-) to the ChoP(+) phenotype was observed as
      early as day 3 after intranasal inoculation. Chinchillas colonized by strains
      with the ChoP(+) phenotype demonstrated a significantly higher level of NTHI 2019
      per milliliter of nasal lavage fluid than chinchillas colonized with
      predominantly the ChoP(-) variant (P < 0.05). The concentration of cells with the
      ChoP(+) phenotype in the middle ear was 3 log units higher than that of cells
      with the ChoP(-) variant (P < 0.01). There was a statistically significant
      association between ChoP(+) expression in the nasal lavage and the development of
      OM with culture-positive middle ear fluids in this model. These data suggest that
      expression of the ChoP(+) phenotype promotes enhanced nasopharyngeal colonization
      and development of OM.

PMID- 10899861
TI  - Switching of flagellar motility in Helicobacter pylori by reversible length
      variation of a short homopolymeric sequence repeat in fliP, a gene encoding a
      basal body protein.
AB  - The genome of Helicobacter pylori contains numerous simple nucleotide repeats
      that have been proposed to have regulatory functions and to compensate for the
      conspicuous dearth of master regulatory pathways in this highly host-adapted
      bacterium. H. pylori strain 26695, whose genomic sequence was determined by The
      Institute for Genomic Research (TIGR), contains a repeat of nine cytidines in the
      fliP flagellar basal body gene that splits the open reading frame in two parts.
      In this work, we demonstrate that the 26695(C9) strain with a split fliP gene as
      sequenced by TIGR was nonflagellated and nonmotile. In contrast, earlier isolates
      of strain 26695 selected by positive motility testing as well as pig-passaged
      derivatives of 26695 were all flagellated and highly motile. All of these motile
      strains had a C(8) repeat and consequently a contiguous fliP reading frame. By
      screening approximately 50,000 colonies of 26695(C9) for motility in soft agar, a
      motile revertant with a C(8) repeat could be isolated, proving that the described
      switch is reversible. The fliP genes of 20 motile clinical H. pylori isolates
      from different geographic regions possessed intact fliP genes with repeats of
      eight cytidines or the sequence CCCCACCC in its place. Isogenic fliP mutants of a
      motile, C(8) repeat isolate of strain 26695 were constructed by allelic exchange
      mutagenesis and found to be defective in flagellum biogenesis. Mutants produced
      only small amounts of flagellins, while the transcription of flagellin genes
      appeared unchanged. These results strongly suggest a unique mechanism regulating
      motility in H. pylori which relies on slipped-strand mispairing-mediated
      mutagenesis of fliP.

PMID- 10899862
TI  - Differential protein expression in phenotypic variants of Streptococcus
      pneumoniae.
AB  - Streptococcus pneumoniae undergoes spontaneous phase variation resulting in
      opaque and transparent colony forms. Differences in colony opacity correlate with
      differences in virulence: the transparent variants are more capable of colonizing
      the nasopharynx, whereas the opaque variants show increased virulence during
      systemic infections. To gain insight into the pathogenesis of pneumococcal
      disease at the molecular level, protein expression patterns of the phenotypic
      variants of two pneumococcal strains were compared by high-resolution two
      dimensional protein electrophoresis. In comparison with transparent variants, the
      opaque variants reduced the expression of two proteins and overexpressed one
      protein. The proteins were identified by mass spectrometric analysis. The protein
      overexpressed in the opaque phenotype revealed significant homology to elongation
      factor Ts of Helicobacter pylori. One of the two proteins that were
      underexpressed in the opaque variants revealed significant homology to the
      proteinase maturation protein PrtM of Lactocobacillus paracasei, a member of the
      family of peptidyl-prolyl cis/trans isomerases. A consensus lipoprotein signal
      sequence suggests that the putative proteinase maturation protein A, designated
      PpmA, is located at the surface of the pneumococcus and may play a role in the
      maturation of surface or secreted proteins. The second underexpressed protein was
      identified as pyruvate oxidase, SpxB. The lower SpxB expression in opaque
      variants most probably explains the reduced production of hydrogen peroxide, a
      reaction product of SpxB, in this variant. Since a spxB-defective pneumococcal
      mutant has decreased ability to colonize the nasopharynx (B. Spellerberg, D. R.
      Cundell, J. Sandros, B. J. Pearce, I. Idanpaan-Heikkila, C. Rosenow, and H. R.
      Masure, 1996. Mol. Microbiol. 19:803-813, 1996), our data suggest that SpxB plays
      an important role in enhancing the ability of transparent variants to efficiently
      colonize the nasopharynx.

PMID- 10899863
TI  - Novel apoptosis-inducing activity in Bacteroides forsythus: a comparative study
      with three serotypes of Actinobacillus actinomycetemcomitans.
AB  - Bacteroides forsythus, which has been reported to be associated with
      periodontitis but has not been recognized as a key pathogen, was found to induce
      cytolytic activity against HL-60 and other human leukemic cells. This cytolytic
      activity was demonstrated according to three different criteria: (i) loss of both
      mitochondrial membrane potential and membrane integrity in cells treated with
      bacterial extracts and then with Rh123 and propidium iodide, respectively, as
      demonstrated by flow cytometry; (ii) damage to cytoplasmic membrane, as revealed
      by scanning electron microscopy (SEM); and (iii) DNA ladder formation and
      activation of caspase-3. These results indicate that B. forsythus produced an
      apoptosis-inducing factor(s) found to be composed of protein as judged by heat
      and trypsin sensitivity. In addition to extracts from B. forsythus, the culture
      supernatant of this bacterium has the ability to induce a cytolytic effect
      against peripheral white blood cells, especially lymphocytes. For comparison with
      B. forsythus, the same analyses were applied to two strains with different
      serotypes of Actinobacillus actinomycetemcomitans, serotypes a (ATCC 43717) and c
      (ATCC 43719), in addition to previously reported apoptosis-inducing serotype b
      (ATCC 43718), which was used as a positive control. The strains of A.
      actinomycetemcomitans serotypes a and b induced apoptosis in HL-60 cells as
      judged by the above three criteria but to a slightly lesser extent than did B.
      forsythus, while the serotype c strain produced apoptosis to a negligible extent.
      Detailed SEM images showed that the A. actinomycetemcomitans serotype a strain
      induced large-pore formation and the serotype b strain produced small pores with
      typical blebbing, while B. forsythus induced severe membrane ruffling. Further
      DNA ladder formation and caspase-3 activation were observed in the serotype a and
      b strains but not in the serotype c strain. The present paper is the first report
      of a protein factor(s) from B. forsythus and the A. actinomycetemcomitans
      serotype a strain which induces apoptotic cell death.

PMID- 10899864
TI  - Cloning of genes of nontypeable Haemophilus influenzae involved in penetration
      between human lung epithelial cells.
AB  - Haemophilus influenzae penetrates between epithelial cells via an unknown
      mechanism. A chromosomal library of nonencapsulated H. influenzae strain A960053
      DNA was constructed in Escherichia coli DH5alpha to identify bacterial genes
      contributing to this paracytosis. Two E. coli clones that contained open reading
      frames (ORFs) homologous to HI0636 to HI0641 of H. influenzae strain Rd and that
      showed an increased penetration in epithelial cell layers of the human bronchial
      epithelial cell line NCI-H292 were identified. ORFs HI0636 and HI0638, encoding
      two small proteins of unknown functions, were further investigated. The clone
      containing ORFs HI0636 and HI0637 as well as the clone containing ORF HI0638
      showed a significant increase in penetration. Disruption of HI0638 by kanamycin
      box insertion in H. influenzae strain A960053 resulted in loss of penetration
      into the epithelial cell layers. Disruption of HI0636 had no effect on
      penetration in this model system. Since a role for HI0637 in the paracytosis of
      H. influenzae is very unlikely because it encodes TrpS, we conclude that the
      protein encoded by ORF HI0638 may function as a paracytin, while that encoded by
      HI0636 may have an auxiliary function.

PMID- 10899865
TI  - CTLA-4 down-regulates the protective anticryptococcal cell-mediated immune
      response.
AB  - Cell-mediated immune (CMI) responses defined by delayed-type hypersensitivity
      (DTH) reactivity to cryptococcal culture filtrate antigen (CneF) can be either
      protective or nonprotective against an infection with Cryptococcus neoformans.
      The protective and nonprotective anticryptococcal DTH responses are induced by
      different immunogens and have differing activated-T-cell profiles. This study
      examined the effects of blockade of the interaction between cytotoxic T
      lymphocyte antigen 4 (CTLA-4) and its ligands B7-1 (CD80) and B7-2 (CD86) on the
      anticryptococcal DTH responses and protection. We found that CTLA-4 blockade at
      the time of immunization with the immunogen that induces the protective response,
      CneF, in complete Freund's adjuvant (CFA) or the immunogen that induces the
      nonprotective response, heat-killed cryptococcal cells (HKC), enhanced
      anticryptococcal DTH reactivity. In contrast, blocking CTLA-4 after the immune
      response was induced failed to enhance responses. Blockade of CTLA-4 in an
      infection model resulted in earlier development of the anticryptococcal CMI
      response than in control mice. Concomitant with increases in DTH reactivity in
      mice treated with anti-CTLA-4 Fab fragments at the time of immunization, there
      were decreases in cryptococcal CFU in lungs, spleens, and brains compared to
      controls. Blockade of CTLA-4 resulted in long-term protection, as measured by
      significantly increased survival times, only in mice given the protective
      immunogen, CneF-CFA. Anti-CTLA-4 treatment did not shift the response induced by
      the nonprotective immunogen, HKC, to a long-term protective one. Our data
      indicate that blockade of CTLA-4 interactions with its ligands may be useful in
      enhancing host defenses against C. neoformans.

PMID- 10899866
TI  - Prophylactic and therapeutic efficacy of antibodies to a capsular polysaccharide
      shared among vancomycin-sensitive and -resistant enterococci.
AB  - Enterococci are important nosocomial pathogens that are increasingly difficult to
      treat due to intrinsic and acquired resistance to antibiotics, including
      vancomycin. A recently described capsular polysaccharide (CP) isolated from
      Enterococcus faecalis 12030 was used to evaluate the potential efficacy of active
      or passive immunotherapy regimens as adjunctive treatments. Evaluation of
      protective efficacy was carried out in immunocompetent mice challenged
      intravenously (i.v.) with live enterococci. In nonimmune mice, i.v. inoculations
      resulted in high levels of bacteria in kidneys, spleens, and livers 5 days after
      challenge. Mice immunized with four 10-microg doses of CP antigen/mouse were
      protected against challenge with the homologous E. faecalis strain. High-titer
      opsonic immunoglobulin G was also induced by immunizing rabbits with the purified
      CP, and passive transfer of this antiserum to mice produced significantly lower
      bacterial counts in organs than did normal rabbit serum or sterile saline.
      Antibodies to the polysaccharide isolated from E. faecalis 12030 were protective
      against Enterococcus faecalis OG1RF and against two serologically related,
      vancomycin-resistant Enterococcus faecium clinical isolates. Antibodies to this
      CP antigen were also effective as a therapeutic reagent in mice when passive
      therapy was initiated 48 h after live bacterial challenge. These data indicate
      that CP antigens from enterococci are potential targets of protective antibodies
      and that these antibodies may be useful for prophylaxis and treatment of
      enterococcal infections.

PMID- 10899867
TI  - Expression of intimin gamma from enterohemorrhagic Escherichia coli in
      Citrobacter rodentium.
AB  - The carboxy-terminal 280 amino acids (Int280) of the bacterial adhesion molecule
      intimin include the receptor-binding domain. At least five different types of
      Int280, designated alpha, beta, gamma, delta, and epsilon, have been described
      based on sequence variation in this region. Importantly, the intimin types are
      associated with different evolutionary branches and contribute to distinct tissue
      tropism of intimin-positive bacterial pathogens. In this study we engineered a
      strain of Citrobacter rodentium, which normally displays intimin beta, to express
      intimin gamma from enterohemorrhagic Escherichia coli. We show that intimin gamma
      binds to the translocated intimin receptor (Tir) from C. rodentium and has the
      ability to produce attaching and effacing lesions on HEp-2 cells. However, C.
      rodentium expressing intimin gamma could not colonize orally infected mice or
      induce mouse colonic hyperplasia. These results suggest that intimin may
      contribute to host specificity, possibly through its interaction with a receptor
      on the host cell surface.

PMID- 10899868
TI  - Constitutive expression of the Vi polysaccharide capsular antigen in attenuated
      Salmonella enterica serovar typhi oral vaccine strain CVD 909.
AB  - Live oral Ty21a and parenteral Vi polysaccharide vaccines provide significant
      protection against typhoid fever, albeit by distinct immune mechanisms. Vi
      stimulates serum immunoglobulin G Vi antibodies, whereas Ty21a, which does not
      express Vi, elicits humoral and cell-mediated immune responses other than Vi
      antibodies. Protection may be enhanced if serum Vi antibody as well as cell
      mediated and humoral responses can be stimulated. Disappointingly, several new
      attenuated Salmonella enterica serovar Typhi oral vaccines (e.g., CVD 908-htrA
      and Ty800) that elicit serum O and H antibody and cell-mediated responses
      following a single dose do not stimulate serum Vi antibody. Vi expression is
      regulated in response to environmental signals such as osmolarity by controlling
      the transcription of tviA in the viaB locus. To investigate if Vi antibodies can
      be stimulated if Vi expression is rendered constitutive, we replaced P(tviA) in
      serovar Typhi vaccine CVD 908-htrA with the constitutive promoter P(tac),
      resulting in CVD 909. CVD 909 expresses Vi even under high-osmolarity conditions
      and is less invasive for Henle 407 cells. In mice immunized with a single
      intranasal dose, CVD 909 was more immunogenic than CVD 908-htrA in eliciting
      serum Vi antibodies (geometric mean titer of 160 versus 49, P = 0.0007), whereas
      O antibody responses were virtually identical (geometric mean titer of 87 versus
      80). In mice challenged intraperitoneally with wild-type serovar Typhi 4 weeks
      after a single intranasal immunization, the mortality of those immunized with CVD
      909 (3 of 8) was significantly lower than that of control mice (10 of 10, P =
      0.043) or mice given CVD 908-htrA (9 of 10, P = 0.0065).

PMID- 10899869
TI  - L-Arginine availability modulates local nitric oxide production and parasite
      killing in experimental trypanosomiasis.
AB  - Nitric oxide (NO) is an important effector molecule of the immune system in
      eliminating numerous pathogens. Peritoneal macrophages from Trypanosoma brucei
      brucei-infected mice express type II NO synthase (NOS-II), produce NO, and kill
      parasites in the presence of L-arginine in vitro. Nevertheless, parasites
      proliferate in the vicinity of these macrophages in vivo. The present study shows
      that L-arginine availability modulates NO production. Trypanosomes use L-arginine
      for polyamine synthesis, required for DNA and trypanothione synthesis. Moreover,
      arginase activity is up-regulated in macrophages from infected mice from the
      first days of infection. Arginase competes with NOS-II for their common
      substrate, L-arginine. In vitro, arginase inhibitors decreased urea production,
      increased macrophage nitrite production, and restored trypanosome killing. In
      vivo, a dramatic decrease in L-arginine concentration was observed in plasma from
      infected mice. In situ restoration of NO production and trypanosome killing were
      observed when excess L-arginine, but not D-arginine or L-arginine plus N(omega)
      nitro-L-arginine (a NOS inhibitor), was injected into the peritoneum of infected
      mice. These data indicate the role of L-arginine depletion, induced by arginase
      and parasites, in modulating the L-arginine-NO pathway under pathophysiological
      conditions.

PMID- 10899870
TI  - Characterization of adherence of nontypeable Haemophilus influenzae to human
      epithelial cells.
AB  - The adherence of 58 nontypeable Haemophilus influenzae isolates obtained from
      patients with otitis media or chronic obstructive pulmonary disease (COPD) and
      obtained from the throats of healthy individuals to Chang and NCI-H292 epithelial
      cells was compared. Otitis media isolates, but not COPD isolates, adhered
      significantly more to both cell lines than did throat isolates. Since high
      molecular-weight (HMW) proteins are major adhesins of nontypeable H. influenzae,
      the isolates were screened for HMW protein expression by Western blotting with
      two polyclonal sera and PCR with hmw-specific primers. Twenty-three of the 32
      adhering isolates (72%) and only 1 of the 26 nonadherent strains were HMW protein
      or hmw gene positive. Among the 32 isolates adhering to either cell line, 5
      different adherence patterns were distinguished based on the inhibiting effect of
      dextran sulfate. Using H. influenzae strain 12 expressing two well-defined HMW
      proteins (HMW1 and HMW2) and its isogenic mutants as a reference, we observed
      HMW1-like adherence to both cell lines for 16 of the 32 adherent isolates. Four
      others showed HMW2-like adherence to NCI-H292. Of the three other patterns of
      adherence, one probably also involved HMW protein. Screening of the isolates with
      six HMW-specific monoclonal antibodies in a whole-cell enzyme-linked
      immunosorbent assay showed that the HMW proteins of COPD isolates and carrier
      isolates were more distinct from the HMW proteins from H. influenzae strain 12
      than those from otitis media isolates. Characterization of the HMW protein of a
      COPD isolate by adherence and DNA sequence analysis showed that despite large
      sequence diversity in the hmwA gene, probably resulting in the antigenic
      differences, the HMW protein mediated the HMW2-like adherence of this strain.

PMID- 10899871
TI  - Interleukin-10 has different effects on proliferation of Listeria monocytogenes
      in livers and spleens of mice.
AB  - The aim of this study was to investigate the effect of interleukin-10 (IL-10) on
      the course of Listeria monocytogenes infection in naive and immune mice.
      Treatment with IL-10 during the course of a primary infection significantly
      decreased the number of bacteria in the spleen and did not affect the number in
      the liver. During a secondary infection in immune mice treated with IL-10, the
      number of bacteria was significantly lower in the spleen but significantly higher
      in the liver in comparison to mock-treated immune mice. IL-10 treatment during a
      primary Listeria infection decreased the concentration of gamma interferon (IFN
      gamma) in plasma and the toxoplasmastatic activity of macrophages, whereas it
      increased the percentage of mildly CD3-positive T cells in the spleen. During a
      secondary infection, the concentration of IFN-gamma in plasma was decreased on
      day 1 but remained unaffected during later days of infection. From these results,
      we conclude that IL-10 has different effects on the proliferation of L.
      monocytogenes in the spleen and liver during primary and secondary Listeria
      infections.

PMID- 10899872
TI  - Role of phosphoglucomutase of Bordetella bronchiseptica in lipopolysaccharide
      biosynthesis and virulence.
AB  - The phosphoglucomutase (PGM)-encoding gene of Bordetella bronchiseptica is
      required for lipopolysaccharide (LPS) biosynthesis. An insertion mutant of the
      wild-type B. bronchiseptica strain BB7865 which disrupted LPS biosynthesis was
      created and characterized (BB7865pgm). Genetic analysis of the mutated gene
      showed it shares high identity with PGM genes of various bacterial species and
      forms part of an operon which also encompasses the gene encoding phosphoglucose
      isomerase. Functional assays for PGM revealed that enzyme activity is expressed
      in both bvg-positive and bvg-negative strains of B. bronchiseptica and is
      substantially reduced in BB7865pgm. Complementation of the mutated PGM gene with
      that from BB7865 restored the wild-type condition for all phenotypes tested. The
      ability of the mutant BB7865pgm to survive within J774. A1 cells was
      significantly reduced at 2 h (40% reduction) and 24 h (56% reduction)
      postinfection. BB7865pgm was also significantly attenuated in its ability to
      survive in vivo following intranasal infection of mice, being effectively cleared
      from the lungs within 4 days, whereas the wild-type strain persisted at least 35
      days. The activities of superoxide dismutase, urease, and acid phosphatase were
      unaffected in the PGM-deficient strain. In contrast, the inability to produce
      wild-type LPS resulted in a reduced bacterial resistance to oxidative stress and
      a higher susceptibility to the antimicrobial peptide cecropin P.

PMID- 10899874
TI  - Failure To detect muramic acid in normal rat tissues but detection in
      cerebrospinal fluids from patients with Pneumococcal meningitis.
AB  - Muramic acid serves as a marker for the presence of bacterial cell wall debris in
      mammalian tissues. There have been a number of controversial and sometimes
      conflicting results on assessing the levels of muramic acid in health and
      disease. The present report is the first to use the state-of-the art technique,
      gas chromatography-tandem mass spectrometry, to identify and quantify the levels
      of muramic acid in tissues. Muramic acid was not found in normal rat brain or
      spleen. However, when tissues were spiked with muramic acid, it was readily
      identified. The detection limit was <1 ng of muramic acid/100 mg (wet weight) of
      tissue. The levels of muramic acid reported in diseased human spleen and spleen
      of arthritic rats, previously injected with bacterial cell walls, were 100- to
      1,000-fold higher. In the present study, muramic acid was also readily detected
      in the cerebrospinal fluid of patients with pneumococcal meningitis (6.8 to 3,900
      ng of muramic acid/ml of cerebrospinal fluid). In summary, there can be an
      enormous difference in the levels of muramic acid found in different mammalian
      tissues and body fluids in health and disease. This report could have great
      impact in future studies assessing the role of bacterial cell wall remnants in
      the pathogenesis of certain human inflammatory diseases.

PMID- 10899873
TI  - Toll-like receptor 4-deficient mice have reduced bone destruction following mixed
      anaerobic infection.
AB  - C3H/HeJ mice have an impaired ability to respond to lipopolysaccharide (LPS) due
      to a mutation in the gene that encodes Toll-like receptor 4 (TLR4). The effect of
      TLR4 deficiency on host responses to endodontic infections is unknown. In the
      present study, we compared periapical bone destruction, sepsis, and inflammatory
      cytokine production in LPS-hyporesponsive C3H/HeJ and wild-type control C3H/HeOuJ
      mice. The mandibular first molars of both strains were subjected to pulpal
      exposure and infection with a mixture of four anaerobic pathogens, Prevotella
      intermedia, Fusobacterium nucleatum, Streptococcus intermedius, and
      Peptostreptococcus micros. At sacrifice on day 21, TLR4-deficient C3H/HeJ mice
      had significantly reduced periapical bone destruction compared to wild-type
      C3H/HeOuJ mice (P < 0.001). The decreased bone destruction in C3H/HeJ correlated
      with reduced expression of the bone resorptive cytokines interleukin 1alpha (IL
      1alpha) (P < 0.01) and IL-1beta (P < 0.05) as well as the proinflammatory
      cytokine IL-12 (P < 0.05). No significant differences were seen in the levels of
      gamma interferon, tumor necrosis factor alpha (TNF-alpha), or IL-10 between the
      two strains. The expression of IL-1alpha, IL-1beta, TNF-alpha, IL-10, and IL-12
      were all significantly reduced in vitro in macrophages from both TLR4-deficient
      C3H/HeJ and C57BL/10ScNCr strains, compared to wild-type controls. Notably, the
      responses of TLR4-deficient macrophages to both gram-positive and gram-negative
      bacteria were similarly reduced. Neither C3H/HeJ nor C3H/HeOuJ mice exhibited
      orofacial abscess development or infection dissemination as determined by
      splenomegaly or cachexia. We conclude that intact TLR function mediates increased
      proinflammatory responses and bone destruction in response to mixed anaerobic
      infections.

PMID- 10899875
TI  - Influence of platelets and platelet microbicidal protein susceptibility on the
      fate of Staphylococcus aureus in an in vitro model of infective endocarditis.
AB  - Several lines of evidence indicate that platelets protect against endovascular
      infections such as infective endocarditis (IE). It is highly likely that a
      principal mechanism of this platelet host defense role is the release of platelet
      microbicidal proteins (PMPs) in response to agonists generated at sites of
      endovascular infection. We studied the ability of platelets to limit the
      colonization and proliferation of Staphylococcus aureus in an in vitro model of
      IE. Three isogenic S. aureus strains, differing in their in vitro susceptibility
      to thrombin-induced platelet microbicidal protein-1 (tPMP), were used: ISP479C
      (parental strain; highly susceptible to tPMP [tPMP(s)]); ISP479R (transposon
      mutant derived from ISP479; tPMP resistant [tPMP(r)]); or 757-5 (tPMP(r)
      transductant of the ISP479R genotype in the ISP479 parental background). Time
      kill assays and in vitro IE models were used to examine the temporal relationship
      between thrombin-induced platelet activation and S. aureus killing. In time-kill
      studies, early platelet activation (30 min prior to bacterial exposure)
      correlated with a significant bactericidal effect against tPMP(s) ISP479C (r(2) >
      0.90, P < 0.02) but not against tPMP(r) strains, ISP479R or 757-5. In the IE
      model, thrombin activation significantly inhibited proliferation of ISP479C
      within simulated vegetations compared to strains ISP479R or 757-5 (P < 0.05). The
      latter differences were observed despite there being no detectable differences
      among the three S. aureus strains in initial colonization of simulated
      vegetations. Collectively, these data indicate that platelets limit
      intravegetation proliferation of tPMP(s) but not tPMP(r) S. aureus. These
      findings underscore the likelihood that platelets play an important antimicrobial
      host defense role in preventing and/or limiting endovascular infections due to
      tPMP(s) pathogens.

PMID- 10899876
TI  - Ultrastructure of Rickettsia rickettsii actin tails and localization of
      cytoskeletal proteins.
AB  - Actin-based motility (ABM) is a mechanism for intercellular spread that is
      utilized by vaccinia virus and the invasive bacteria within the genera
      Rickettsia, Listeria, and Shigella. Within the Rickettsia, ABM is confined to
      members of the spotted fever group (SFG), such as Rickettsia rickettsii, the
      agent of Rocky Mountain spotted fever. Infection by each agent induces the
      polymerization of host cell actin to form the typical F (filamentous)-actin comet
      tail. Assembly of the actin tail propels the pathogen through the host cytosol
      and into cell membrane protrusions that can be engulfed by neighboring cells,
      initiating a new infectious cycle. Little is known about the structure and
      morphogenesis of the Rickettsia rickettsii actin tail relative to Shigella and
      Listeria actin tails. In this study we examined the ultrastructure of the
      rickettsial actin tail by confocal, scanning electron, and transmission electron
      microscopy. Confocal microscopy of rhodamine phalloidin-stained infected Vero
      cells revealed the typhus group rickettsiae, Rickettsia prowazekii and Rickettsia
      typhi, to have no actin tails and short (approximately 1- to 3-micrometer)
      straight or hooked actin tails, respectively. The SFG rickettsia, R. rickettsii,
      displayed long actin tails (>10 micrometer) that were frequently comprised of
      multiple, distinct actin bundles, wrapping around each other in a helical
      fashion. Transmission electron microscopy, in conjunction with myosin S1
      subfragment decoration, revealed that the individual actin filaments of R.
      rickettsii tails are >1 micrometer long, arranged roughly parallel to one
      another, and oriented with the fast-growing barbed end towards the rickettsial
      pole. Scanning electron microscopy of intracellular rickettsiae demonstrated R.
      rickettsii to have polar associations of cytoskeletal material and R. prowazekii
      to be devoid of cytoskeletal interactions. By indirect immunofluorescence, both
      R. rickettsii and Listeria monocytogenes actin tails were shown to contain the
      cytoskeletal proteins vasodilator-stimulated phosphoprotein profilin, vinculin,
      and filamin. However, rickettsial tails lacked ezrin, paxillin, and tropomyosin,
      proteins that were associated with actin tails of cytosolic or protrusion-bound
      Listeria. The unique ultrastructural and compositional characteristics of the R.
      rickettsii actin tail suggest that rickettsial ABM is mechanistically different
      from previously described microbial ABM systems.

PMID- 10899877
TI  - Bile mediates intestinal pathology in endotoxemia in rats.
AB  - Intestinal pathology frequently accompanies experimental endotoxic shock and is
      mediated by proinflammatory cytokines. Our hypotheses are that hepatobiliary
      factors operating from the luminal side of the gut make a major contribution to
      this damage and that tumor necrosis factor alpha (TNF-alpha) is involved in the
      pathology. We treated rats with lipopolysaccharide (LPS) intravenously and found
      that external drainage of bile totally protected the gastrointestinal tract,
      macroscopically and microscopically, 4 h after LPS administration and
      dramatically improved survival of the animals for 48 h after LPS administration.
      The concentration of TNF-alpha in bile increased markedly after LPS
      administration and was over 30 times higher in bile than in serum. Tissue damage
      and the biliary TNF-alpha response were abrogated when animals were pretreated
      with gadolinium chloride to eliminate Kupffer cells. TNF-alpha infusion into the
      duodenal lumen caused intestinal damage similar to that elicited by intravenous
      LPS. In rats treated with LPS, survival was significantly increased during the
      first 36 h in animals given an infusion of anti-TNF-alpha antibody into the
      duodenum. These results demonstrate that in endotoxemia, intestinal damage is
      mediated by factors derived from the bile. The findings indicate that luminally
      acting TNF-alpha contributes to the intestinal damage.

PMID- 10899878
TI  - Down-regulation of GATA-2 transcription during Pneumocystis carinii infection.
AB  - Differences in gene expression between Pneumocystis carinii-infected and
      noninfected rats were examined. Total RNA was isolated from homogenized rat lungs
      and then subjected to differential display with combinations of oligo(dT) and
      various arbitrary PCR primers. Approximately 50 differentially expressed bands
      were observed. Several of these DNA bands were isolated, reamplified, and cloned.
      The cloned DNA fragments were used as probes to perform Northern hybridization on
      RNA from P. carinii-infected and noninfected rat lungs. One clone was found to
      react with a 3-kb mRNA from noninfected but not from P. carinii-infected rat
      lung, suggesting that the gene represented by this clone was down-regulated
      during P. carinii infection. The nucleotide sequence of this clone was determined
      and found to be 97% homologous to the mouse GATA-2 transcription factor. In situ
      hybridization using RNA probes derived from this clone revealed that alveolar
      macrophages, resident lung monocytes, and bronchial epithelial cells express the
      GATA-2 gene in the lung.

PMID- 10899879
TI  - Antigenic and sequence diversity in gonococcal transferrin-binding protein A.
AB  - Neisseria gonorrhoeae is a gram-negative pathogen that is capable of satisfying
      its iron requirement with human iron-binding proteins such as transferrin and
      lactoferrin. Transferrin-iron utilization involves specific binding of human
      transferrin at the cell surface to what is believed to be a complex of two iron
      regulated, transferrin-binding proteins, TbpA and TbpB. The genes encoding these
      proteins have been cloned and sequenced from a number of pathogenic, gram
      negative bacteria. In the current study, we sequenced four additional tbpA genes
      from other N. gonorrhoeae strains to begin to assess the sequence diversity among
      gonococci. We compared these sequences to those from other pathogenic bacteria to
      identify conserved regions that might be important for the structure and function
      of these receptors. We generated polyclonal mouse sera against synthetic peptides
      deduced from the TbpA sequence from gonococcal strain FA19. Most of these
      synthetic peptides were predicted to correspond to surface-exposed regions of
      TbpA. We found that, while most reacted with denatured TbpA in Western blots,
      only one antipeptide serum reacted with native TbpA in the context of intact
      gonococci, consistent with surface exposure of the peptide to which this serum
      was raised. In addition, we evaluated a panel of gonococcal strains for antigenic
      diversity using these antipeptide sera.

PMID- 10899880
TI  - Nonopsonic phagocytosis of zymosan and Mycobacterium kansasii by CR3 (CD11b/CD18)
      involves distinct molecular determinants and is or is not coupled with NADPH
      oxidase activation.
AB  - Complement receptor type 3 (CR3) was initially described as an opsonic receptor.
      Subsequently, CR3-mediated lectin-sugar recognition mechanisms have been shown to
      play a major role in the nonopsonic phagocytosis of several pathogens, among them
      Mycobacterium tuberculosis. Little is known about the binding and signal
      transduction mechanisms operating during nonopsonic ingestion through CR3 of
      different microorganisms. In the present study, we used CHO cells stably
      transfected with CR3 to show that CR3 was able to mediate internalization of
      zymosan and pathogenic mycobacteria (Mycobacterium kansasii and Mycobacterium
      avium) but not that of nonpathogenic species (Mycobacterium smegmatis and
      Mycobacterium phlei). A combination of mannan and beta-glucan inhibited the
      phagocytosis of zymosan but had no effect on M. kansasii ingestion. Among six
      monoclonal antibodies (MAbs) directed against the CD11b subunit of CR3 that
      decreased zymosan ingestion, only three inhibited M. kansasii phagocytosis. In
      particular, MAbs known to block the CR3 lectin site affected only internalization
      of zymosan. Using U937 macrophages, we observed that zymosan ingestion through
      CR3 induced superoxide production measured by cytochrome c reduction and by
      translocation of the NADPH oxidase cytosolic component p47phox to the phagosomal
      membrane, whereas phagocytosis of viable or heat-killed M. kansasii did not.
      Furthermore, lack of superoxide anion production during phagocytosis of M.
      kansasii was not due to inhibition of NADPH oxidase per se or superoxide anion
      scavenging. Together, our results indicate that (i) nonopsonic phagocytosis of
      zymosan and M. kansasii by CR3 implicates different molecular mechanisms
      involving multiple and distinct epitopes of CD11b and (ii) CR3 may transduce
      different cellular responses depending on the sites mediating nonopsonic
      phagocytosis.

PMID- 10899881
TI  - Interleukin-1 receptor signaling rather than that of tumor necrosis factor is
      critical in protecting the host from the severe consequences of a polymicrobe
      anaerobic infection.
AB  - Infection of the dental pulp leads to an osteolytic lesion that results from a
      polymicrobial infection consisting largely of pathogenic anaerobes. Infection
      causes significant morbidity and mortality mediated by bacterial factors and in
      some cases by the up-regulation of inflammatory cytokines. The inflammatory
      cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF), in particular,
      play a complex and central role in the responses to microbial pathogens. However,
      relatively little is known about the significance of these cytokines in
      protecting the host from focal polymicrobial anaerobic infections. To establish
      the relative importance of IL-1 and TNF in mediating the response to a mixed
      anaerobic infection, we inoculated the dental pulp of mice with six anaerobic
      pathogens containing functional deletions of receptors to IL-1 (IL-1R1(-/-)), TNF
      (TNFRp55(-/-)-p75(-/-)), or both (TNFRp55(-/-)-IL-1RI(-/-)). The results indicate
      that IL-1 receptor signaling and TNF receptor signaling both play similarly
      important roles in protecting the host from local tissue damage. However, IL-1
      receptor signaling is considerably more important than TNF receptor signaling in
      preventing the spread of infection into surrounding fascial planes, since IL-1R1(
      /-) but not TNFRp55(-/-)-p75(-/-) mice exhibited significantly higher morbidity
      and mortality. Moreover, all of the fatal infections occurred in male mice,
      suggesting the importance of gender differences in limiting the impact of these
      infections.

PMID- 10899882
TI  - Interleukin-10 gene therapy-mediated amelioration of bacterial pneumonia.
AB  - Respiratory infection by Actinobacillus pleuropneumoniae causes a highly
      pathogenic necrotizing pleuropneumonia with severe edema, hemorrhage and fever.
      Acute infection is characterized by expression of inflammatory cytokines,
      including interleukin-1 (IL-1), IL-6 and IL-8. To determine if high level
      production of inflammatory cytokines contributed to disease pathogenesis, we
      investigated if inhibiting macrophage activation with adenovirus type 5-expressed
      IL-10 (Ad-5/IL-10) reduced the severity of acute disease. Porcine tracheal
      epithelial cells infected with Ad-5/IL-10 produced bioactive human IL-10. When
      pigs were intratracheally infected with A. pleuropneumoniae, pigs pretreated with
      Ad-5/IL-10 showed a significant reduction in the amount of lung damage when
      compared to adenovirus type 5-expressing beta-galactosidase (Ad-5/beta-Gal)
      treated and untreated pigs. In addition, serum zinc levels were unchanged, the
      lung weight/body weight ratio (an indicator of vascular leakage) was
      significantly reduced, and lung pathology scores were reduced. Myeloperoxidase
      activity in lung lavage fluid samples, an indicator of neutrophil invasion, was
      decreased to levels similar to that seen in pigs not infected with A.
      pleuropneumoniae. Reduction in inflammatory cytokine levels in lung lavage fluid
      samples correlated with the clinical observations in that pigs pretreated with Ad
      5/IL-10 showed a corresponding reduction of IL-1 and tumor necrosis factor (TNF)
      compared with untreated and Ad-5/beta-Gal-treated pigs. IL-6 levels were
      unaffected by pretreatment with Ad-5/IL-10, consistent with observations that IL
      6 was not derived from alveolar macrophages. Since inflammatory cytokines are
      expressed at high levels in acute bacterial pleuropneumonia, these results
      indicate that macrophage activation, involving overproduction of IL-1 and TNF, is
      a prime factor in infection-related cases of massive lung injury.

PMID- 10899883
TI  - Decorin-binding protein A (DbpA) of Borrelia burgdorferi is not protective when
      immunized mice are challenged via tick infestation and correlates with the lack
      of DbpA expression by B. burgdorferi in ticks.
AB  - Previous studies showed that decorin-binding protein A (DbpA) of Borrelia
      burgdorferi was a protective immunogen in the murine model of Lyme borreliosis
      when mice were challenged (needle inoculated) intradermally with in vitro
      cultivated spirochetes. In the present study, DbpA-immunized C3H/HeJ mice were
      not protected from infection when infested with Ixodes scapularis nymphs
      harboring virulent B. burgdorferi 297. This lack of protection correlated with
      the failure to detect DbpA on B. burgdorferi in ticks, suggesting that DbpA is
      not available as a target for bactericidal antibodies in serum when B.
      burgdorferi-infected ticks take their blood meal from an immunized host. The
      failure of DbpA immunization to protect tick-challenged mice contradicts the
      results of earlier needle inoculation vaccination experiments and suggests that
      DbpA may not be suitable as a Lyme disease vaccine.

PMID- 10899884
TI  - Chlamydia pneumoniae induces inflammatory changes in the heart and aorta of
      normocholesterolemic C57BL/6J mice.
AB  - Chlamydia pneumoniae infection induces inflammatory changes in blood vessels in
      normocholesterolemic rabbits, but it is not known whether the same phenomenon
      occurs in other animal models. Thus, in this study, C57BL/6J mice were inoculated
      with C. pneumoniae. Inflammatory changes in the heart or aorta were observed in a
      small number of chronically infected mice. No evidence of atherosclerotic lesions
      was found in any of the mice. These findings suggest that chronic C. pneumoniae
      infection can induce inflammatory changes in the heart and aorta of C57BL/6J
      mice, but does not initiate definitive atherosclerosis.

PMID- 10899885
TI  - Immunohistochemical study of lymphocyte populations infiltrating the gastric
      mucosa of beagle dogs experimentally infected with Helicobacter pylori.
AB  - Experimental infection of beagle dogs with Helicobacter pylori induces
      recruitment to the gastric mucosae of neutrophils at early stages and later of
      mononuclear cells that organize into lymphoid follicles. These structures become
      macroscopically evident and consist of peripheral CD4(+) T lymphocytes and
      central CD21(+) B lymphocytes. Furthermore, transient expression of interleukin-8
      (IL-8) parallels the presence of neutrophils in the gastric mucosae, whereas
      expression of IL-6 tends to persist chronically.

PMID- 10899886
TI  - Characterization of the Streptococcus mutans pyruvate formate-lyase (PFL)
      activating enzyme gene by complementary reconstitution of the In vitro PFL
      reactivating system.
AB  - The act gene was identified and an act mutant as well as the pfl mutant was
      constructed in Streptococcus mutans. Pyruvate formate-lyase (PFL) activity was
      regenerated with the mixture of the respective cell extracts from these mutants
      by complementary reconstitution of the in vitro reactivating system. The S.
      mutans act gene encoded the sole enzyme able to activate the PFL protein in this
      organism.

PMID- 10899887
TI  - [Cu,Zn]-Superoxide dismutase mutants of the swine pathogen Actinobacillus
      pleuropneumoniae are unattenuated in infections of the natural host.
AB  - Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia,
      contains a periplasmic Cu- and Zn-cofactored superoxide dismutase ([Cu,Zn]-SOD,
      or SodC) which has the potential, realized in other pathogens, to promote
      bacterial survival during infection by dismutating host-defense-derived
      superoxide. Here we describe the construction of a site-specific, [Cu,Zn]-SOD
      deficient A. pleuropneumoniae serotype 1 mutant and show that although the mutant
      is highly sensitive to the microbicidal action of superoxide in vitro, it remains
      fully virulent in experimental pulmonary infection in pigs.

PMID- 10899888
TI  - Salmonella enterica serovars gallinarum and pullorum expressing Salmonella
      enterica serovar typhimurium type 1 fimbriae exhibit increased invasiveness for
      mammalian cells.
AB  - Salmonella enterica serovars Gallinarum and Pullorum are S. enterica biotypes
      that exhibit host specificity for poultry and aquatic birds and are not normally
      capable of causing disease in mammalian hosts. During their evolution toward host
      restriction serovars Gallinarum and Pullorum lost their ability to mediate
      mannose-sensitive hemagglutination (MSHA), a phenotype correlated with adherence
      to certain cell types. Because adherence is an essential requirement for invasion
      of cells by bacterial pathogens, we examined whether MHSA type 1 fimbriae would
      increase the ability of serovars Pullorum and Gallinarum to invade normally
      restrictive cells. Serovars Gallinarum and Pullorum expressing S. enterica
      serovar Typhimurium strain LT2 type 1 fimbriae exhibited a 10- to 20-fold
      increased ability to adhere to and a 20- to 60-fold increased invasion efficiency
      of the human epithelial HEp-2 cell line. Invasion was accompanied by extensive
      ruffling of the membranes of the HEp-2 cells. In a murine ligated ileal loop
      model, a 32% increase in the number of M-cell ruffles was seen when serovar
      Gallinarum expressed serovar Typhimurium type 1 fimbriae.

PMID- 10899889
TI  - Nonimmune interaction of the SfbI protein of Streptococcus pyogenes with the
      immunoglobulin G F(ab')(2) fragment.
AB  - Fibronectin-binding protein I (SfbI) of Streptococcus pyogenes binds to mouse
      immunoglobulin G (IgG) but not to IgA or IgM in a nonimmune fashion. The
      fibronectin-binding domains of SfbI were responsible for this activity, which was
      targeted to the IgG F(ab')(2) fragment. SfbI also binds to B cells but not to
      CD4(+) or CD8(+) lymphocytes.

PMID- 10899890
TI  - Critical role of neutrophils in eliminating Listeria monocytogenes from the
      central nervous system during experimental murine listeriosis.
AB  - Neutrophils are the main inflammatory cell present in lesions involving the
      central nervous system (CNS) during human and murine listeriosis. In this study,
      administration of the neutrophil-depleting monoclonal antibody RB6-8C5 during
      experimental murine listeriosis facilitated the multiplication of Listeria
      monocytogenes in the CNS. These data suggest that neutrophils play a key role in
      eliminating bacteria that gain access to the CNS compartment. In addition, we
      provide evidence that their migration into the CNS may be necessary for the
      subsequent recruitment of macrophages and activated lymphocytes.

PMID- 10899891
TI  - Streptococcus pneumoniae induces secretion of vascular endothelial growth factor
      by human neutrophils.
AB  - Infection by pneumococci causes an acute inflammatory response associated with
      neutrophil influx, increased vascular permeability, and edema. Vascular
      endothelial growth factor (VEGF) is one of the most potent regulators of
      endothelial permeability. In vitro stimulation of neutrophils showed that
      pneumococci and purified pneumococcal cell wall induce VEGF secretion,
      independent of the presence of pneumolysin or polysaccharide capsule. The results
      of this study indicate VEGF is secreted in pneumococcal disease, suggesting a
      role as a mediator of increased vascular permeability.

PMID- 10899892
TI  - Sunlight-induced propagation of the lysogenic phage encoding cholera toxin.
AB  - In toxigenic Vibrio cholerae, the cholera enterotoxin (CT) is encoded by CTXPhi,
      a lysogenic bacteriophage. The propagation of this filamentous phage can result
      in the origination of new toxigenic strains. To understand the nature of possible
      environmental factors associated with the propagation of CTXPhi, we examined the
      effects of temperature, pH, salinity, and exposure to direct sunlight on the
      induction of the CTX prophage and studied the transmission of the phage to
      potential recipient strains. Exposure of cultures of CTXPhi lysogens to direct
      sunlight resulted in approximately 10,000-fold increases in phage titers.
      Variation in temperature, pH, or salinity of the culture did not have a
      substantial effect on the induction of the prophage, but these factors influenced
      the stability of CTXPhi particles. Exposure of mixed cultures of CTXPhi lysogens
      and potential recipient strains to sunlight significantly increased both the in
      vitro and in vivo (in rabbit ileal loops) transduction of the recipient strains
      by CTXPhi. Included in these transduction experiments were two environmental
      nontoxigenic (CTXPhi(-)) strains of V. cholerae O139. These two O139 strains were
      transduced at high efficiency by CTXPhi, and the phage genome integrated into the
      O139 host chromosome. The resulting CTXPhi lysogens produced biologically active
      CT both in vitro and in rabbit ileal loops. This finding suggests a possible
      mechanism explaining the origination of toxigenic V. cholerae O139 strains from
      nontoxigenic progenitors. This study indicates that sunlight is a significant
      inducer of the CTX prophage and suggests that sunlight-induced transmission of
      CTXPhi may constitute part of a natural mechanism for the origination of new
      toxigenic strains of V. cholerae.

PMID- 10899893
TI  - Dominant nonresponsiveness to Helicobacter pylori infection is associated with
      production of interleukin 10 but not gamma interferon.
AB  - Helicobacter pylori-induced gastritis is an essential precursor lesion for the
      development of peptic ulcers or gastric adenocarcinoma. We demonstrate that
      nonresponsiveness to H. pylori SS1 infection is dominantly inherited in mice.
      F(1) hybrid crosses between a nonresponder mouse and three responder strains all
      possessed the nonresponder phenotype. Secretion of interleukin-10 but not gamma
      interferon was associated with nonresponsiveness to infection.

PMID- 10899894
TI  - Antigen specificity of T-cell response to Mycobacterium avium infection in mice.
AB  - T cells from Mycobacterium avium-infected C57BL/6 mice reacted to culture
      filtrate, envelope, and cytosol proteins and to fractions obtained from these
      proteins. Multiple targets were recognized, such as 29- to 45-kDa and <21-kDa
      antigens of the culture filtrate, antigens of around 30 kDa in the envelope and
      cytosol, and 45- to 116-kDa proteins in the envelope.

PMID- 10899895
TI  - Pseudomonas aeruginosa exoenzyme S induces transcriptional expression of
      proinflammatory cytokines and chemokines.
AB  - Pseudomonas aeruginosa infection of cystic fibrosis patients causes lung damage
      that is substantially orchestrated by cytokines. In this study, multi-gene probe
      analysis was used to characterize the ability of the P. aeruginosa mitogen,
      exoenzyme S, to induce proinflammatory and immunoregulatory cytokines and
      chemokines. Exoenzyme S strongly induced transcription of proinflammatory
      cytokines and chemokines (tumor necrosis factor alpha, interleukin-1alpha [IL
      1alpha], IL-1beta, IL-6, IL-8, MIP-1alpha, MIP-1beta, MCP-1, RANTES, and I-309),
      modest transcription of immunoregulatory cytokines (IL-10 and IL-12p40), and weak
      transcription of Th1 cytokines (IL-2 and gamma interferon). The response occurred
      early and subsided without evolving over time. These data suggest that cells
      responding to exoenzyme S would rapidly express proinflammatory cytokines and
      chemokines that may contribute to pulmonary inflammation in cystic fibrosis.

PMID- 10899896
TI  - Polymorphism of repeated regions of pertactin in Bordetella pertussis, Bordetella
      parapertussis, and Bordetella bronchiseptica.
AB  - Pertactin is an outer membrane protein expressed by Bordetella pertussis,
      Bordetella parapertussis, and Bordetella bronchiseptica that induces protective
      immunity to Bordetella infections. The immunodominant and immunoprotective
      epitopes of pertactin include two repeated regions, I and II. Comparison of these
      two repeated regions showed that B. parapertussis pertactin is invariant, whereas
      B. pertussis pertactin varies mostly in region I and B. bronchiseptica pertactin
      varies in both repeated regions I and II, but mostly in region II. These
      differences may result from specific characteristics of these Bordetella species.

PMID- 10899897
TI  - Role of monocytes in experimental Staphylococcus aureus endocarditis.
AB  - In the pathogenesis of bacterial endocarditis (BE), the clotting system plays a
      cardinal role in the formation and maintenance of the endocardial vegetations.
      The extrinsic pathway is involved in the activation of the coagulation pathway
      with tissue factor (TF) as the key protein. Staphylococcus aureus is a frequently
      isolated bacterium from patients with BE. We therefore investigated whether S.
      aureus can induce TF activity (TFA) on fibrin-adherent monocytes, used as an in
      vitro model of BE. We also assessed in vivo in rabbits with catheter induced
      vegetations, the effect of S. aureus infection on vegetational TFA. In vitro
      experiments showed that adherent S. aureus induced TFA on fibrin-adherent
      monocytes which was optimal at a bacterium/monocyte ratio of 1 to 1. Monocyte
      damage occurred when this ratio exceeded 4 to 1 (visually) or 6 to 1 (propidium
      iodide influx) Consequently, TFA decreased. In vivo S. aureus led to very high
      bacterial numbers in the vegetations and a significant increase of their weight.
      However, TFA of infected vegetations was the same as of sterile ones. This may be
      due to the high bacteria to monocyte ratio as well as bacterium-induced monocyte
      damage. Teicoplanin treatment of infected rabbits reduced bacterial numbers in
      the blood and in the vegetations. Two-day treatment resulted in an increase of
      vegetational TFA, but after four-day treatment vegetational TFA dropped, most
      probably due to a suboptimal bacterium/monocyte ratio. S. aureus endocarditis in
      etoposide (Vepesid)-treated rabbits, leading to a selective monocytopenia, caused
      a rapid death of the animals. In these rabbits no vegetations were found at all.
      We conclude that, like Streptococcus sanguis and Staphylococcus epidermidis, S.
      aureus is able to induce TFA in fibrin-adherent blood monocytes. In addition,
      monocytes have a protective effect during the course of S. aureus endocarditis.

PMID- 10899898
TI  - Differential infectivity and division of Toxoplasma gondii in human peripheral
      blood leukocytes.
AB  - When tachyzoites were incubated with human peripheral blood leukocytes in vitro,
      more monocytes and dendritic cells than neutrophils or lymphocytes were infected.
      Although tachyzoites were able to divide in each of these cell types, monocytes
      and dendritic cells were more permissive to rapid tachyzoite division than
      neutrophils or lymphocytes.

PMID- 10899899
TI  - Lipoarabinomannans activate the protein tyrosine kinase Hck in human neutrophils.
AB  - The mycobacterial lipoarabinomannans (LAMs) are glycosylphosphatidyl-myo-inositol
      anchored lipoglycans with diverse biological activities. It has been shown that
      purified LAMs interact directly, or indirectly, through receptors with the plasma
      membrane receptors of target cells located in domains rich in
      glycosylphosphatidylinositol-anchored proteins that contain Src family protein
      tyrosine kinases. To examine whether LAMs could activate Src-related kinases,
      human neutrophils were exposed to mannosylated LAMs (ManLAMs) purified from the
      vaccinal strain Mycobacterium bovis BCG and to phosphoinositol-capped LAMs
      (AraLAM or PILAM) obtained from the nonpathogenic species Mycobacterium
      smegmatis. We report first that both ManLAMs and PILAMs activate Hck in a rapid
      and transient manner and second that complete deacylation of ManLAM abolished its
      effect on Hck activity, thereby demonstrating that acylation of LAM but not
      mannosylation is critical for Hck activation. These data indicate that Hck is
      involved in the signaling pathway of LAMs, molecules known for their ability to
      trigger several responses in eukaryotic cells.

PMID- 10899900
TI  - Role of Nramp1 deletion in Chlamydia infection in mice.
AB  - Elicited macrophages from 129sv mice with a functional deletion of the natural
      resistance-associated macrophage protein 1 gene (Nramp1) were shown to be as
      susceptible as wild-type mice to infection with the Chlamydia trachomatis mouse
      pneumonitis and L3 serovars and to Chlamydia pneumoniae. Furthermore, the two
      groups of mice were shown to be similarly susceptible to an intranasal infection
      with these microorganisms. In conclusion, the Nramp1 gene does not appear to play
      a major role in the regulation of the susceptibility of mice to a chlamydial
      infection.

PMID- 10899901
TI  - Identification of saliva-regulated genes of Streptococcus gordonii DL1 by
      differential display using random arbitrarily primed PCR.
AB  - Attachment of Streptococcus gordonii to the acquired pellicle of the tooth
      surface involves specific interactions between bacterial adhesins and adsorbed
      salivary components. To study saliva-regulated gene expression in S. gordonii, we
      used random arbitrarily primed PCR (RAP-PCR). Bacteria were incubated in either
      brain heart infusion medium or saliva. Total RNA from both conditions was
      purified and RAP fingerprinted and then PCR amplified with an arbitrary primer.
      The differentially displayed DNA fragments were cloned, sequenced, and analyzed
      using the BLAST search network service. Three DNA products were up-regulated. One
      was identified as that of the sspA and -B genes, which encode the salivary
      agglutinin glycoprotein-binding proteins SspA and SspB of S. gordonii; another
      had 79% identity with the Lactococcus lactis clpE gene, encoding a member of the
      Clp protease family; and the third product showed no significant homology to
      known genes. Five down-regulated genes were identified which encode proteins
      involved in bacterial metabolism. We have shown, for the first time, direct
      induction of sspA and -B in S. gordonii by human saliva.

PMID- 10899902
TI  - Blockade of transforming growth factor beta/Smad signaling in T cells by
      overexpression of Smad7 enhances antigen-induced airway inflammation and airway
      reactivity.
AB  - Transforming growth factor (TGF)-beta has been implicated in immunosuppression.
      However, it remains obscure whether regulation of T cells by TGF-beta contributes
      to the immunosuppression in vivo. To address this issue, we developed transgenic
      mice expressing Smad7, an intracellular antagonist of TGF-beta/Smad signaling,
      selectively in mature T cells using a plasmid construct coding a promoter element
      (the distal lck promoter) that directs high expression in peripheral T cells.
      Peripheral T cells were not growth inhibited by TGF-beta in Smad7 transgenic
      mice. Although Smad7 transgenic mice did not spontaneously show a specific
      phenotype, antigen-induced airway inflammation and airway reactivity were
      enhanced in Smad7 transgenic mice associated with high production of both T
      helper cell type 1 (Th1) and Th2 cytokines. Thus, blockade of TGF-beta/Smad
      signaling in mature T cells by expression of Smad7 enhanced airway inflammation
      and airway reactivity, suggesting that regulation of T cells by TGF-beta was
      crucial for negative regulation of the inflammatory (immune) response. Our
      findings also implicated TGF-beta/Smad signaling in mature T cells as a
      regulatory component of allergic asthma.

PMID- 10899903
TI  - Metabolic consequences of adenosine deaminase deficiency in mice are associated
      with defects in alveogenesis, pulmonary inflammation, and airway obstruction.
AB  - Adenosine deaminase (ADA) is a purine catabolic enzyme that manages levels of the
      biologically active purines adenosine and 2'-deoxyadenosine in tissues and cells.
      ADA-deficient mice die at 3 wk of age from severe respiratory distress. This
      phenotype is progressive and is linked to perturbations in pulmonary purine
      metabolism. The inflammatory changes found in the lungs of ADA-deficient mice
      included an accumulation of activated alveolar macrophages and eosinophils. These
      changes were accompanied by a pronounced enlargement of alveolar spaces and
      increases in mucus production in the bronchial airways. The alveolar enlargement
      was found to be due in part to abnormal alveogenesis. Lowering adenosine and 2'
      deoxyadenosine levels using ADA enzyme therapy decreased the pulmonary
      eosinophilia and resolved many of the lung histopathologies. In addition,
      genetically restoring ADA to the forestomach of otherwise ADA-deficient mice
      prevented adenine metabolic disturbances as well as lung inflammation and damage.
      These data suggest that disturbances in purinergic signaling mediate the lung
      inflammation and damage seen in ADA-deficient mice.

PMID- 10899904
TI  - Ras mediates effector pathways responsible for pre-B cell survival, which is
      essential for the developmental progression to the late pre-B cell stage.
AB  - Ras is essential for the transition from early B cell precursors to the pro-B
      stage, and is considered to be involved in the signal cascade mediated by pre-B
      cell antigen receptors. To examine the role of p21(ras) in the late stage of B
      cell differentiation, we established transgenic mice (TG) expressing a dominant
      inhibitory mutant of Ha-ras (Asn-17 Ha-ras) in B lineage cells at high levels
      after the early B cell precursor stage. Expression of p21(Asn-17) (Ha-ras) was
      associated with a prominent reduction in the number of late pre-B cells, but had
      little effect on proliferation of early pre-B cells. Inhibition of p21(ras)
      activity markedly reduced the life span of pre-B cells, due, at least in part, to
      downregulation of the expression of an antiapoptotic protein, Bcl-xL. Thus, the
      apparent role for p21(ras) activity in pre-B cell survival may explain the
      decreased numbers of late pre-B cells in Asn-17 Ha-ras TG. Consistent with this
      possibility, overexpression of Bcl-2 in Asn-17 Ha-ras TG reversed the reduction
      in the number of late pre-B cells undergoing immunoglobulin light chain gene
      (IgL) rearrangement and progressing to immature B cells. These results suggest
      that p21(ras) mediates effector pathways responsible for pre-B cell survival,
      which is essential for progression to the late pre-B and immature B stages.

PMID- 10899905
TI  - A macrophage invasion mechanism for mycobacteria implicating the extracellular
      domain of CD43.
AB  - We studied the role of CD43 (leukosialin/sialophorin), the negatively charged
      sialoglycoprotein of leukocytes, in the binding of mycobacteria to host cells.
      CD43-transfected HeLa cells bound Mycobacterium avium, but not Salmonella
      typhimurium or Shigella flexneri. Quantitative bacteriology showed that
      macrophages (M(phi)) from wild-type mice (CD43(+/+)) bound M. avium,
      Mycobacterium bovis (bacillus Calmette-Guerin), and Mycobacterium tuberculosis
      (strain H37Rv), whereas M(phi) from CD43 knockout mice (CD43(-/)-) did not.
      Fluorescence microscopy demonstrated that the associated M. avium had been
      ingested by the CD43(+/+) M(phi). The inability of CD43(-/)- M(phi) to bind M.
      avium could be restored by addition of galactoglycoprotein (Galgp), the
      extracellular mucin portion of CD43. The effect of Galgp is not due to
      opsonization of the bacteria, but required its interaction with the M(phi) other
      mucins had no effect. CD43 expression by the M(phi) was also required for optimal
      induction by M. avium of tumor necrosis factor (TNF)-alpha production, which
      likewise could be reconstituted by Galgp. In contrast, interleukin (IL)-10
      production by M. avium-infected M(phi) was CD43 independent, demonstrating
      discordant regulation of TNF-alpha and IL-10. These findings describe a novel
      role of CD43 in promoting stable interaction of mycobacteria with receptors on
      the M(phi) enabling the cells to respond specifically with TNF-alpha production.

PMID- 10899906
TI  - Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac
      1 (CD11b/CD18).
AB  - The firm adhesion and transplatelet migration of leukocytes on vascular thrombus
      are both dependent on the interaction of the leukocyte integrin, Mac-1, and a
      heretofore unknown platelet counterreceptor. Here, we identify the platelet
      counterreceptor as glycoprotein (GP) Ibalpha, a component of the GP Ib-IX-V
      complex, the platelet von Willebrand factor (vWf) receptor. THP-1 monocytic cells
      and transfected cells that express Mac-1 adhered to GP Ibalpha-coated wells.
      Inhibition studies with monoclonal antibodies or receptor ligands showed that the
      interaction involves the Mac-1 I domain (homologous to the vWf A1 domain), and
      the GP Ibalpha leucine-rich repeat and COOH-terminal flanking regions. The
      specificity of the interaction was confirmed by the finding that neutrophils from
      wild-type mice, but not from Mac-1-deficient mice, bound to purified GP Ibalpha
      and to adherent platelets, the latter adhesion being inhibited by pretreatment of
      the platelets with mocarhagin, a protease that specifically cleaves GP Ibalpha.
      Finally, immobilized GP Ibalpha supported the rolling and firm adhesion of THP-1
      cells under conditions of flow. These observations provide a molecular target for
      disrupting leukocyte-platelet complexes that promote vascular inflammation in
      thrombosis, atherosclerosis, and angioplasty-related restenosis.

PMID- 10899907
TI  - CC chemokine receptor (CCR)2 is required for langerhans cell migration and
      localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of
      CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state
      dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic
      inflammation.
AB  - There is growing evidence that chemokines and their receptors regulate the
      movement and interaction of antigen-presenting cells such as dendritic cells
      (DCs) and T cells. We tested the hypothesis that the CC chemokine receptor (CCR)2
      and CCR5 and the chemokine macrophage inflammatory protein (MIP)-1alpha, a ligand
      for CCR5, influence DC migration and localization. We found that deficiency of
      CCR2 but not CCR5 or MIP-1alpha led to distinct defects in DC biology. Langerhans
      cell (skin DC) density in CCR2-null mice was normal, and their ability to migrate
      into the dermis was intact; however, their migration to the draining lymph nodes
      was markedly impaired. CCR2-null mice had lower numbers of DCs in the spleen, and
      this was primarily due to a reduction in the CD8alpha(1) T helper cell type 1
      (Th1)-inducing subset of DCs. Additionally, there was a block in the Leishmania
      major infection-induced relocalization of splenic DCs from the marginal zone to
      the T cell areas. We propose that these DC defects, in conjunction with increased
      expression of B lymphocyte chemoattractant, a B cell-specific chemokine, may
      collectively contribute to the striking B cell outgrowth and Th2 cytokine-biased
      nonhealing phenotype that we observed in CCR2-deficient mice infected with L.
      major. This disease phenotype in mice with an L. major-resistant genetic
      background but lacking CCR2 is strikingly reminiscent of that observed typically
      in mice with an L. major-susceptible genetic background. Thus, CCR2 is an
      important determinant of not only DC migration and localization but also the
      development of protective cell-mediated immune responses to L. major.

PMID- 10899908
TI  - Natural interferon alpha/beta-producing cells link innate and adaptive immunity.
AB  - Innate immune responses to pathogens critically impact the development of
      adaptive immune responses. However, it is not completely understood how innate
      immunity controls the initiation of adaptive immunities or how it determines
      which type of adaptive immunity will be induced to eliminate a given pathogen.
      Here we show that viral stimulation not only triggers natural interferon (IFN)
      alpha/beta-producing cells (IPCs) to produce vast amounts of antiviral IFN
      alpha/beta but also induces these cells to differentiate into dendritic cells
      (DCs). IFN-alpha/beta and tumor necrosis factor alpha produced by virus-activated
      IPCs act as autocrine survival and DC differentiation factors, respectively. The
      virus-induced DCs stimulate naive CD4(+) T cells to produce IFN-gamma and
      interleukin (IL)-10, in contrast to IL-3-induced DCs, which stimulate naive
      CD4(+) T cells to produce T helper type 2 cytokines IL-4, IL-5, and IL-10. Thus,
      IPCs may play two master roles in antiviral immune responses: directly inhibiting
      viral replication by producing large amounts of IFN-alpha/beta, and subsequently
      triggering adaptive T cell-mediated immunity by differentiating into DCs. IPCs
      constitute a critical link between innate and adaptive immunity.

PMID- 10899909
TI  - Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide
      synthase in experimental salmonellosis. I. Effects on microbial killing by
      activated peritoneal macrophages in vitro.
AB  - The contribution of the NADPH phagocyte oxidase (phox) and inducible nitric oxide
      (NO) synthase (iNOS) to the antimicrobial activity of macrophages for Salmonella
      typhimurium was studied by using peritoneal phagocytes from C57BL/6, congenic
      gp91phox(-/)-, iNOS(-/)-, and doubly immunodeficient phox(-/)-iNOS(-/)- mice. The
      respiratory burst and NO radical (NO.) made distinct contributions to the anti
      Salmonella activity of macrophages. NADPH oxidase-dependent killing is confined
      to the first few hours after phagocytosis, whereas iNOS contributes to both early
      and late phases of antibacterial activity. NO-derived species initially synergize
      with oxyradicals to kill S. typhimurium, and subsequently exert prolonged oxidase
      independent bacteriostatic effects. Biochemical analyses show that early killing
      of Salmonella by macrophages coincides with an oxidative chemistry characterized
      by superoxide anion (O(2).(-)), hydrogen peroxide (H(2)O(2)), and peroxynitrite
      (ONOO(-)) production. However, immunofluorescence microscopy and killing assays
      using the scavenger uric acid suggest that peroxynitrite is not responsible for
      macrophage killing of wild-type S. typhimurium. Rapid oxidative bacterial killing
      is followed by a sustained period of nitrosative chemistry that limits bacterial
      growth. Interferon gamma appears to augment antibacterial activity predominantly
      by enhancing NO. production, although a small iNOS-independent effect was also
      observed. These findings demonstrate that macrophages kill Salmonella in a
      dynamic process that changes over time and requires the generation of both
      reactive oxidative and nitrosative species.

PMID- 10899910
TI  - Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide
      synthase in experimental salmonellosis. II. Effects on microbial proliferation
      and host survival in vivo.
AB  - The roles of the NADPH phagocyte oxidase (phox) and inducible nitric oxide
      synthase (iNOS) in host resistance to virulent Salmonella typhimurium were
      investigated in gp91phox(-/)-, iNOS(-/)-, and congenic wild-type mice. Although
      both gp91phox(-/)- and iNOS(-/)- mice demonstrated increased susceptibility to
      infection with S. typhimurium compared with wild-type mice, the kinetics of
      bacterial replication were dramatically different in the gp91phox(-/)- and iNOS(
      /)- mouse strains. Greater bacterial numbers were present in the spleens and
      livers of gp91phox(-/)- mice compared with C57BL/6 controls as early as day 1 of
      infection, and all of the gp91phox(-/)- mice succumbed to infection within 5 d.
      In contrast, an increased bacterial burden was detected within
      reticuloendothelial organs of iNOS(-/)- mice only beyond the first week of
      infection. Influx of inflammatory CD11b(+) cells, granuloma formation, and serum
      interferon gamma levels were unimpaired in iNOS(-/)- mice, but the iNOS-deficient
      granulomas were unable to limit bacterial replication. The NADPH phagocye oxidase
      and iNOS are both required for host resistance to wild-type Salmonella, but
      appear to operate principally at different stages of infection.

PMID- 10899911
TI  - Salmonella exploits caspase-1 to colonize Peyer's patches in a murine typhoid
      model.
AB  - Salmonella typhimurium invades host macrophages and induces apoptosis and the
      release of mature proinflammatory cytokines. SipB, a protein translocated by
      Salmonella into the cytoplasm of macrophages, is required for activation of
      Caspase-1 (Casp-1, an interleukin [IL]-1beta-converting enzyme), which is a
      member of a family of cysteine proteases that induce apoptosis in mammalian
      cells. Casp-1 is unique among caspases because it also directly cleaves the
      proinflammatory cytokines IL-1beta and IL-18 to produce bioactive cytokines. We
      show here that mice lacking Casp-1 (casp-1(-/)- mice) had an oral S. typhimurium
      50% lethal dose (LD(50)) that was 1,000-fold higher than that of wild-type mice.
      Salmonella breached the M cell barrier of casp-1(-/)- mice efficiently; however,
      there was a decrease in the number of apoptotic cells, intracellular bacteria,
      and the recruitment of polymorphonuclear lymphocytes in the Peyer's patches (PP)
      as compared with wild-type mice. Furthermore, Salmonella did not disseminate
      systemically in the majority of casp-1(-/)- mice, as demonstrated by
      significantly less colonization in the PP, mesenteric lymph nodes, and spleens of
      casp-1(-/)- mice after an oral dose of S. typhimurium that was 100-fold higher
      than the LD(50). The increased resistance in casp-1(-/)- animals appears specific
      for Salmonella infection since these mice were susceptible to colonization by
      another enteric pathogen, Yersinia pseudotuberculosis, which normally invades the
      PP. These results show that Casp-1, which is both proapoptotic and
      proinflammatory, is essential for S. typhimurium to efficiently colonize the
      cecum and PP and subsequently cause systemic typhoid-like disease in mice.

PMID- 10899912
TI  - Interferon gamma contributes to initiation of uterine vascular modification,
      decidual integrity, and uterine natural killer cell maturation during normal
      murine pregnancy.
AB  - The dominant lymphocytes in human and murine implantation sites are transient,
      pregnancy-associated uterine natural killer (uNK) cells. These cells are a major
      source of interferon (IFN)-gamma. Implantation sites in mice lacking uNK cells
      (alymphoid recombinase activating gene [RAG]-2(-/)- common cytokine receptor
      chain gamma [gamma(c)](-/)-) or IFN-gamma signaling (IFN-gamma(-/)- or IFN
      gammaRalpha(-/)-) fail to initiate normal pregnancy-induced modification of
      decidual arteries and display hypocellularity or necrosis of decidua. To
      investigate the functions of uNK cell-derived IFN-gamma during pregnancy, RAG-2(
      /)-gamma(c)(-/)- females were engrafted with bone marrow from IFN-gamma(-/)-
      mice, IFN-gamma signal-disrupted mice (IFN-gammaRalpha(-/)- or signal transducer
      and activator of transcription [Stat]-1(-/)-), or from mice able to establish
      normal uNK cells (severe combined immunodeficient [SCID] or C57BL/6). Mated
      recipients were analyzed at midgestation. All grafts established uNK cells.
      Grafts from IFN-gamma(-/)- mice did not reverse host vascular or decidual
      pathology. Grafts from all other donors promoted modification of decidual
      arteries and decidual cellularity. Grafts from IFN-gammaRalpha(-/)- or Stat-1(-/)
      mice overproduced uNK cells, all of which were immature. Grafts from IFN-gamma(
      /)-, SCID, or C57BL/6 mice produced normal, mature uNK cells. Administration of
      murine recombinant IFN-gamma to pregnant RAG-2(-/)-gamma(c)(-/)- mice initiated
      decidual vessel modification and promoted decidual cellularity in the absence of
      uNK cells. These in vivo findings strongly suggest that uNK cell-derived IFN
      gamma modifies the expression of genes in the uterine vasculature and stroma,
      which initiates vessel instability and facilitates pregnancy-induced remodeling
      of decidual arteries.

PMID- 10899914
TI  - Human CD1b and CD1c isoforms survey different intracellular compartments for the
      presentation of microbial lipid antigens.
AB  - CD1b and CD1c are antigen-presenting molecules that mediate recognition of
      bacterial lipids by T cells, but it is currently not known whether these two
      molecules are redundant or are specialized to perform different immunological
      functions. Here, we show that the distribution of CD1c in human dendritic cells
      was characterized by a high ratio of cell surface to intracellular molecules,
      whereas CD1b showed a reciprocal pattern of distribution. In contrast to the
      accumulation of CD1b in lysosomal major histocompatibility complex class II
      compartments, intracellular CD1c molecules accumulated in other endocytic
      compartments, most likely early and late endosomes. Deletion of the cytoplasmic
      tail of CD1c, containing a tyrosine-based internalization motif, abolished most
      of its intracellular localization. Functional studies using T cells specific for
      defined lipid antigens revealed that in contrast to CD1b-mediated antigen
      presentation, antigen presentation by CD1c was resistant to drugs inhibiting
      endosomal acidification and was independent of endosomal localization of CD1c.
      Taken together, these results support the hypothesis that CD1b and CD1c are
      specialized to survey the lipid content of different intracellular compartments.

PMID- 10899913
TI  - B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components
      of the protective response to influenza virus infection.
AB  - We have studied the role of secreted immunoglobulin (Ig)M in protection from
      infection with influenza virus and delineated the relative contributions of B-1
      versus B-2 cell-derived IgM in this process. Mice deficient in secreted IgM but
      capable of expressing surface IgM and secreting other Ig classes show
      significantly reduced virus clearance and survival rates compared with wild-type
      controls. Irradiation chimeras in which only either B-1 or B-2 cells lack the
      ability to secrete IgM show mortality rates similar to those of mice in which
      neither B-1 nor B-2 cells secrete IgM. Dependence on both sources of IgM for
      survival is partially explained by findings in allotype chimeras that broadly
      cross-reactive B-1 cell-derived natural IgM is present before infection, whereas
      virus strain-specific, B-2 cell-derived IgM appears only after infection.
      Furthermore, lack of IgM secreted from one or both sources significantly impairs
      the antiviral IgG response. Reconstitution of chimeras lacking B-1 cell-derived
      IgM only with IgM-containing serum from noninfected mice improved both survival
      rates and serum levels of virus-specific IgG. Thus, virus-induced IgM must be
      secreted in the presence of natural IgM for efficient induction of specific IgG
      and for immune protection, identifying B-1 and B-2 cell-derived IgM antibodies as
      nonredundant components of the antiviral response.

PMID- 10899915
TI  - Inhibition of hepatitis B virus replication during schistosoma mansoni infection
      in transgenic mice.
AB  - Although coinfection of hepatitis B virus (HBV) and Schistosoma mansoni is a
      frequent event in humans, little is known about the interactions between these
      two pathogens. S. mansoni infection induces T helper cell type 2 (Th2)-type
      cytokines in the liver of humans and mice. The intrahepatic induction of nitric
      oxide (NO) and Th1-type cytokines, such as interferon (IFN)-gamma and IFN
      alpha/beta, inhibits HBV replication noncytopathically in the liver of transgenic
      mice. To examine whether S. mansoni infection and the accompanying induction of
      Th2-type cytokines could interfere with HBV replication in the liver, HBV
      transgenic mice were infected with S. mansoni. By 5 wk after infection, HBV
      replication disappeared concomitant with the intrahepatic induction of NO and Th1
      type cytokines, and in the absence of Th2-type cytokines. By 6-8 wk after
      infection, HBV replication remained undetectable and this was associated with
      further induction of NO and Th1-type cytokines together with the appearance of
      Th2-type cytokines. The S. mansoni-dependent antiviral effect was partially
      blocked by genetically deleting IFN-gamma, although it was unaffected by deletion
      of IFN-alpha/beta. These results indicate that IFN-gamma (probably via NO)
      mediates most of this antiviral activity and that Th2-type cytokines do not
      counteract the antiviral effect of IFN-gamma. Similar events may suppress HBV
      replication during human S. mansoni infection.

PMID- 10899916
TI  - Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the
      function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation.
AB  - It is now clear that functionally specialized regulatory T (Treg) cells exist as
      part of the normal immune repertoire, preventing the development of pathogenic
      responses to both self- and intestinal antigens. Here, we report that the Treg
      cells that control intestinal inflammation express the same phenotype
      (CD25(+)CD45RB(low)CD4(+)) as those that control autoimmunity. Previous studies
      have failed to identify how CD25(+) Treg cells function in vivo. Our studies
      reveal that the immune-suppressive function of these cells in vivo is dependent
      on signaling via the negative regulator of T cell activation cytotoxic T
      lymphocyte-associated antigen 4 (CTLA-4), as well as secretion of the immune
      suppressive cytokine transforming growth factor beta. Strikingly, constitutive
      expression of CTLA-4 among CD4(+) cells was restricted primarily to Treg cells,
      suggesting that CTLA-4 expression by these cells is involved in their immune
      suppressive function. These findings raise the possibility that Treg cell
      function contributes to the immune suppression characteristic of CTLA-4
      signaling. Identification of costimulatory molecules involved in the function of
      Treg cells may facilitate further characterization of these cells and development
      of new therapeutic strategies for the treatment of inflammatory diseases.

PMID- 10899917
TI  - Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells
      constitutively expressing cytotoxic T lymphocyte-associated antigen 4.
AB  - This report shows that cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays
      a key role in T cell-mediated dominant immunologic self-tolerance. In vivo
      blockade of CTLA-4 for a limited period in normal mice leads to spontaneous
      development of chronic organ-specific autoimmune diseases, which are
      immunopathologically similar to human counterparts. In normal naive mice, CTLA-4
      is constitutively expressed on CD25(+)CD4(+) T cells, which constitute 5-10% of
      peripheral CD4(+) T cells. When the CD25(+)CD4(+) T cells are stimulated via the
      T cell receptor in vitro, they potently suppress antigen-specific and polyclonal
      activation and proliferation of other T cells, including CTLA-4-deficient T
      cells, and blockade of CTLA-4 abrogates the suppression. CD28-deficient
      CD25(+)CD4(+) T cells can also suppress normal T cells, indicating that CD28 is
      dispensable for activation of the regulatory T cells. Thus, the CD25(+)CD4(+)
      regulatory T cell population engaged in dominant self-tolerance may require CTLA
      4 but not CD28 as a costimulatory molecule for its functional activation.
      Furthermore, interference with this role of CTLA-4 suffices to elicit autoimmune
      disease in otherwise normal animals, presumably through affecting CD25(+)CD4(+) T
      cell-mediated control of self-reactive T cells. This unique function of CTLA-4
      could be exploited to potentiate T cell-mediated immunoregulation, and thereby to
      induce immunologic tolerance or to control autoimmunity.

PMID- 10899918
TI  - N-Acetylaspartylglutamate: the most abundant peptide neurotransmitter in the
      mammalian central nervous system.
AB  - In the progress of science, as in life, timing is important. The acidic
      dipeptide, N-acetylaspartylglutamate (NAAG), was discovered in the mammalian
      nervous system in 1965, but initially was not considered to be a neurotransmitter
      candidate. In the mid-1980s, a few laboratories revisited the question of NAAG's
      role in the nervous system and pursued hypotheses regarding its function that
      ranged from a precursor for the transmitter pool of glutamate to a direct role as
      a peptide transmitter. Since that time, NAAG has been tested against nearly all
      of the established criteria for identification of a neurotransmitter. It
      successfully meets each of these tests, including a concentrated presence in
      neurons and synaptic vesicles, release from axon endings in a calcium-dependent
      manner following initiation of action potentials, and extracellular hydrolysis by
      membrane-bound peptidase activity. NAAG is the most prevalent and widely
      distributed neuropeptide in the mammalian nervous system. NAAG activates NMDA
      receptors with a low potency that may vary among receptor subtypes, and it is a
      highly selective agonist at the type 3 metabotropic glutamate receptor (mGluR3).
      Acting through this receptor, NAAG reduces cyclic AMP levels, decreases voltage
      dependent calcium conductance, suppresses excitotoxicity, influences long-term
      potentiation and depression, regulates GABA(A) receptor subunit expression, and
      inhibits synaptic release of GABA from cortical neurons. Cloning of peptidase
      activities against NAAG provides opportunities to study the cellular and
      molecular mechanisms by which synaptic NAAG peptidase activity is controlled.
      Given the codistribution of this peptide with a spectrum of traditional
      transmitters and its ability to activate mGluR3, we speculate that one role for
      NAAG following synaptic release is the activation of metabotropic autoreceptors
      that inhibit subsequent transmitter release. A second role is the production of
      extracellular glutamate following NAAG hydrolysis.

PMID- 10899919
TI  - Functions of N-acetyl-L-aspartate and N-acetyl-L-aspartylglutamate in the
      vertebrate brain: role in glial cell-specific signaling.
AB  - N-Acetyl-L-aspartate (NAA) and its derivative N-acetylaspartylglutamate (NAAG)
      are major osmolytes present in the vertebrate brain. Although they are
      synthesized primarily in neurons, their function in these cells is unclear. In
      the brain, these substances undergo intercompartmental cycles in which they are
      released by neurons in a regulated fashion and are then rapidly hydrolyzed by
      catabolic enzymes associated with glial cells. Recently, the catabolic enzyme for
      NAA hydrolysis has been found to be expressed only in oligodendrocytes, and the
      catabolic enzyme for NAAG expressed only in astrocytes. These results indicate an
      unusual tricellular metabolic sequence for the synthesis and hydrolysis of NAAG
      wherein it is synthesized in neurons from NAA and L-glutamate, hydrolyzed to NAA
      and L-glutamate by astrocytes, and further hydrolyzed to L-aspartate and acetate
      by oligodendrocytes. Since the discovery that the NAA and NAAG anabolic products
      of neurons are specifically targeted to oligodendrocytes and astrocytes,
      respectively, this unique metabolic compartmentalization also suggests that these
      substances may play an important role in cell-specific glial signaling. In this
      review, it is hypothesized that a key function of NAA and NAAG in the vertebrate
      brain is in cell signaling and that these substances are important in the
      regulation of interactions of brain cells and in the establishment and
      maintenance of the nervous system.

PMID- 10899920
TI  - Dexamethasone induces lipocalin-type prostaglandin D synthase gene expression in
      mouse neuronal cells.
AB  - Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is responsible for the
      production of PGD(2), the main PG in the CNS. PGD(2) is an endogenous sleep
      inducer, and it is involved in the control of odor and pain responses and body
      temperature. In addition, PGD synthase transports lipophilic molecules in the
      subarachnoid space and CSF. By northern and western assays we show that the
      synthetic glucocorticoid dexamethasone, an inhibitor of PG production in most
      tissues, induces L-PGDS mRNA and protein in a dose- and time-dependent fashion in
      mouse neuronal GT1-7 cells. Accordingly, dexamethasone increases cellular L-PGDS
      enzymatic activity. Dexamethasone induced L-PGDS gene transcription in run-on
      assays and activated the mouse L-PGDS gene promoter in transiently transfected
      cells. It is interesting that the tumor promoter 12-O-tetradecanoyl-phorbol 13
      acetate (TPA), which induces the synthesis of PGs in many tissues, inhibited the
      increase in L-PGDS expression induced by dexamethasone. In contrast, neither
      dexamethasone nor TPA affected the expression of cyclooxygenases-1 and -2. Our
      data demonstrate that dexamethasone induces L-PGDS gene transcription in neuronal
      cells.

PMID- 10899921
TI  - A possible role of alanine for ammonia transfer between astrocytes and
      glutamatergic neurons.
AB  - The metabolism of [U-(13)C]lactate (1 mM) in the presence of unlabeled glucose
      (2.5 mM) was investigated in glutamatergic cerebellar granule cells, cerebellar
      astrocytes, and corresponding co-cultures. It was evident that lactate is
      primarily a neuronal substrate and that lactate produced glycolytically from
      glucose in astrocytes serves as a substrate in neurons. Alanine was highly
      enriched with (13)C in the neurons, whereas this was not the case in the
      astrocytes. Moreover, the cellular content and the amount of alanine released
      into the medium were higher in neurons than astrocytes. On incubation of the
      different cell types in medium containing alanine (1 mM), the astrocytes
      exhibited the highest level of accumulation. Altogether, these results indicate a
      preferential synthesis and release of alanine in glutamatergic neurons and uptake
      in cerebellar astrocytes. A new functional role of alanine may be suggested as a
      carrier of nitrogen from glutamatergic neurons to astrocytes, a transport that
      may operate to provide ammonia for glutamine synthesis in astrocytes and dispose
      of ammonia generated by the glutaminase reaction in glutamatergic neurons. Hence,
      a model of a glutamate-glutamine/lactate-alanine shuttle is presented. To
      elucidate if this hypothesis is compatible with the pattern of alanine metabolism
      observed in the astrocytes and neurons from cerebellum, the cells were incubated
      in a medium containing [(15)N]alanine (1 mM) and [5-(15)N]glutamine (0.5 mM),
      respectively. Additionally, neurons were incubated with [U-(13)C]glutamine to
      estimate the magnitude of glutamine conversion to glutamate. Alanine was labeled
      from [5-(15)N]glutamine to 3.3% and [U-(13)C]glutamate generated from [U
      (13)C]glutamine was labeled to 16%. In spite of the modest labeling in alanine,
      it is clear that nitrogen from ammonia is transferred to alanine via
      transamination with glutamate formed by reductive amination of alpha
      ketoglutarate. With regard to the astrocytic part of the shuttle, glutamine was
      labeled to 22% in one nitrogen atom whereas 3.2% was labeled in two when
      astrocytes were incubated in [(15)N]alanine. Moreover, in co-cultures, [U
      (13)C]alanine labeled glutamate and glutamine equally, whereas [U-(13)C]lactate
      preferentially labeled glutamate. Altogether, these results support the role
      proposed above of alanine as a possible ammonia nitrogen carrier between
      glutamatergic neurons and surrounding astrocytes and they show that lactate is
      preferentially metabolized in neurons and alanine in astrocytes.

PMID- 10899922
TI  - The metabolism of [3-(13)C]lactate in the rat brain is specific of a pyruvate
      carboxylase-deprived compartment.
AB  - Lactate metabolism in the adult rat brain was investigated in relation with the
      concept of lactate trafficking between astrocytes and neurons. Wistar rats were
      infused intravenously with a solution containing either [3-(13)C]lactate (534 mM)
      or both glucose (750 mM) and [3-(13)C]lactate (534 mM). The time courses of both
      the concentration and (13)C enrichment of blood glucose and lactate were
      determined. The data indicated the occurrence of [3-(13)C]lactate recycling
      through liver gluconeogenesis. The yield of glucose labeling was, however,
      reduced when using the glucose-containing infusate. After a 20-min or 1-h
      infusion, perchloric acid extracts of the brain tissue were prepared and
      subsequently analyzed by (13)C- and (1)H-observed/(13)C-edited NMR spectroscopy.
      The (13)C labeling of amino acids indicated that [3-(13)C]lactate was metabolized
      in the brain. Based on the alanine C3 enrichment, lactate contribution to brain
      metabolism amounted to 35% under the most favorable conditions used. By contrast
      with what happens with [1-(13)C]glucose metabolism, no difference in glutamine C2
      and C3 labeling was evidenced, indicating that lactate was metabolized in a
      compartment deprived of pyruvate carboxylase activity. This result confirms, for
      the first time from an in vivo study, that lactate is more specifically a
      neuronal substrate.

PMID- 10899923
TI  - Muscarinic activation of mitogen-activated protein kinase in PC12 cells.
AB  - Muscarinic acetylcholine receptors (mAChRs) activate many downstream signaling
      pathways, some of which can lead to mitogen-activated protein kinase (MAPK)
      phosphorylation and activation. MAPKs play roles in regulating cell growth,
      differentiation, and synaptic plasticity. Here, the activation of MAPK was
      examined in PC12 cells endogenously expressing mAChRs. Western blot analysis
      using a phosphospecific MAPK antibody revealed a dose-dependent and atropine
      sensitive increase in MAPK phosphorylation in cells stimulated with carbachol
      (CCh). The maximal response occurred after 5 min and was rapidly reduced to
      baseline. To investigate the receptors responsible for CCh activation of MAPK in
      PC12 cells, the mAChR subtypes present were determined using RT-PCR and
      immunoprecipitation. RT-PCR was used to amplify fragments of the appropriate
      sizes for m1, m4, and m5, and the identities of the bands were confirmed with
      restriction digests. Immunoprecipitation using subtype-specific antibodies showed
      that approximately 95% of the expressed receptors were m4, whereas the remaining
      approximately 5% were m1 and m5. A highly specific m1 toxin completely blocked
      MAPK phosphorylation in response to CCh stimulation. The mAChR-induced MAPK
      activation was abolished by protein kinase C down-regulation and partially
      inhibited by pertussis toxin. Although m1 represents a small proportion of the
      total mAChR population, pharmacological evidence suggests that m1 is responsible
      for MAPK activation in PC12 cells.

PMID- 10899925
TI  - Cultured granule cells and astrocytes from cerebellum differ in metabolizing
      sphingosine.
AB  - Sphingosine metabolism was studied in primary cultures of differentiated
      cerebellar granule cells and astrocytes. After a 2-h pulse with [C3
      (3)H]sphingosine at different doses (0.1-200 nmol/mg of cell protein), both cell
      types efficiently incorporated the long chain base; the percentage of cellular
      [(3)H]sphingosine over total label incorporation was extremely low at sphingosine
      doses of <10 nmol/mg of cell protein and increased at higher doses. Most of the
      [(3)H]sphingosine taken up underwent metabolic processing by N-acylation, 1
      phosphorylation, and degradation (assessed as (3)H(2)O released in the medium).
      The metabolic processing of exogenous sphingosine was extremely efficient in both
      cells, granule cells and astrocytes being able to metabolize, respectively, an
      amount of sphingosine up to 80- and 300-fold the cellular content of this long
      chain base in 2 h. At the different doses, the prevailing metabolic route of
      sphingosine was different. At lower doses and in a wide dose range, the major
      metabolic fate of sphingosine was N-acylation. With increasing doses, there was
      first increased sphingosine degradation and then increased levels of sphingosine
      1-phosphate. The data demonstrate that, in neurons and astrocytes, the metabolic
      machinery devoted to sphingosine processing is different, astrocytes possessing
      an overall higher capacity to synthesize the bioactive compounds ceramide and
      sphingosine-1-phosphate.

PMID- 10899924
TI  - Brain-derived neurotrophic factor accelerates nitric oxide donor-induced
      apoptosis of cultured cortical neurons.
AB  - Brain-derived neurotrophic factor (BDNF) is known to have important functions in
      neuronal survival, differentiation, and plasticity. In addition to its role as a
      survival-promoting factor, BDNF reportedly can enhance neuronal cell death in
      some cases, for example, the death caused by excitotoxicity or glucose
      deprivation. The cellular mechanism of the death-enhancing effect of BDNF remains
      unknown, in contrast to that of its survival-promoting effect. In this work, we
      found that BDNF markedly accelerated the nitric oxide (NO) donor-induced death of
      cultured embryonic cortical neurons. BDNF increased the number of cells with
      nuclear condensation and DNA fragmentation 24 h after treatment with the NO
      donor, but it did not change the number of those cells 36 h after the treatment.
      The BDNF-accelerated death of cortical neurons was inhibited by the addition of
      actinomycin D or cycloheximide. These results suggest that BDNF can accelerate
      apoptotic cell death elicited by NO donor. TrkB-IgG and K252a blocked the BDNF
      induced acceleration of the death, indicating that the death-accelerating effect
      by BDNF is mediated by TrkB. In addition, the BDNF-accelerated apoptosis was
      inhibited by the addition of SB202190 and SB203580, specific inhibitors of p38
      mitogen-activated protein kinase (MAPK), and U0126, a specific inhibitor of
      MAPK/ERK kinase 1, indicating that the activation of both p38 MAPK and ERK is
      involved in the signaling cascade of the BDNF-accelerated, NO donor-induced
      apoptosis.

PMID- 10899926
TI  - Neuroblastoma cells expressing the noradrenaline transporter are destroyed more
      selectively by 6-fluorodopamine than by 6-hydroxydopamine.
AB  - 6-Hydroxydopamine (6-OHDA) has been used for lesioning catecholaminergic neurons
      and attempted purging of neuroblastoma cells from hematopoietic stem cells in
      autologous bone marrow transplantation (ABMT). Neurotoxicity is mediated
      primarily by reactive oxygen species. In ABMT, 6-OHDA, as a purging agent, has
      been unsuccessful. At physiological pH it autooxidizes before targeted uptake,
      resulting in nonspecific cytotoxicity of nontarget cells. A catecholamine
      analogue, similar to 6-OHDA but with a lower rate of autooxidation enabling
      uptake by target cells, is thus required. Electron paramagnetic resonance spectra
      in this study show that 6-fluorodopamine (6-FDA) hydrolyzes slowly to 6-OHDA at
      physiological pH. Oxygen consumption, H(2)O(2), and quinone production are found
      to be intermediate between those of 6-OHDA and dopamine (DA). Relative
      neurotoxicity of these compounds was assessed by cell viability and DNA damage in
      the human neuroblastoma lines SH-SY5Y and SK-N-LO, which express and lack the
      noradrenaline transporter, respectively. Specific uptake of DA and 6-FDA by SH
      SY5Y cells was demonstrated by competitive m-[(131)I]iodobenzylguanidine uptake
      inhibition. The competition by 6-OHDA was low owing to rapid autooxidation during
      incubation with equal toxicity toward both cell types. 6-FDA toxicity was
      preferential for SH-SY5Y cells and reduced in the presence of desipramine, a
      catecholamine uptake inhibitor. We demonstrate that 6-FDA cytotoxicity is more
      specific for cells expressing catecholamine reuptake systems than is 6-OHDA
      cytotoxicity.

PMID- 10899927
TI  - Protective effect of harmalol and harmaline on MPTP neurotoxicity in the mouse
      and dopamine-induced damage of brain mitochondria and PC12 cells.
AB  - The present study elucidated the protective effect of beta-carbolines (harmaline,
      harmalol, and harmine) on oxidative neuronal damage. MPTP treatment increased
      activities of total superoxide dismutase, catalase, and glutathione peroxidase
      and levels of malondialdehyde and carbonyls in the basal ganglia, diencephalon
      plus midbrain of brain compared with control mouse brain. Coadministration of
      harmalol (48 mg/kg) attenuated the MPTP effect on the enzyme activities and
      formation of tissue peroxidation products. Harmaline, harmalol, and harmine
      attenuated both the 500 microM MPP(+)-induced inhibition of electron flow and
      membrane potential formation and the 100 microM dopamine-induced thiol oxidation
      and carbonyl formation in mitochondria. The scavenging action of beta-carbolines
      on hydroxyl radicals was represented by inhibition of 2-deoxy-D-ribose
      degradation. Harmaline and harmalol (100 microM) attenuated 200 microM dopamine
      induced viability loss in PC12 cells. The beta-carbolines (50 microM) attenuated
      50 microM dopamine-induced apoptosis in PC12 cells. The compounds alone did not
      exhibit significant cytotoxic effects. The results indicate that beta-carbolines
      attenuate brain damage in mice treated with MPTP and MPP(+)-induced mitochondrial
      damage. The compounds may prevent dopamine-induced mitochondrial damage and PC12
      cell death through a scavenging action on reactive oxygen species and inhibition
      of monoamine oxidase and thiol oxidation.

PMID- 10899928
TI  - Apoptosis induced by doxorubicin in neurotumor cells is divorced from drug
      effects on ceramide accumulation and may involve cell cycle-dependent caspase
      activation.
AB  - Doxorubicin (0.5 microgram/ml) induced caspase-dependent apoptosis in SH-SY5Y
      neuroblastoma and CHP-100 neuroepithelioma cells. The apoptotic response started
      to be evident approximately 15 h after drug administration and, as monitored over
      a 48-h period, was more pronounced in CHP-100 than in SH-SY5Y cells. In both
      systems, apoptosis was accompanied by elevation of intracellular ceramide levels.
      Ceramide accumulation was blocked by the ceramide synthase inhibitor fumonisin
      B(1) (25 microM); this compound, however, did not prevent drug-induced apoptosis.
      Untreated cells from both lines expressed negligible p53 levels; on the other
      hand, whereas p53 and p21(Cip1/Waf1) were rapidly up-regulated in doxorubicin
      treated SH-SY5Y cells, such a response was not observed in CHP-100 cells.
      Doxorubicin induced a G(2)/M phase block in both cell lines, but whereas the G(1)
      phase was markedly depleted in CHP-100 cells, it was substantially retained in SH
      SY5Y cells. In the latter system, double G(1) and G(2)/M block largely preceded
      cell death; however, as apoptosis underwent completion, it selectively targeted
      late S and G(2)/M cells. Moreover, apoptosis suppression by caspase inhibition
      did not result in a recovery of the G(1) cell population. These results support
      the notion that doxorubicin-induced apoptosis and ceramide elevation are divorced
      events in neuroectodermal tumors and that p53 function is at least dispensable
      for apoptosis completion. Indeed, as G(1) cells appear to be refractory to
      doxorubicin-induced apoptosis, p53 up-regulation and p21(Cip1/Waf1) expression
      may provide an unfavorable setting for the apoptotic action of the drug.

PMID- 10899930
TI  - Evidence for expression of some microtubule-associated protein 1B in neurons as a
      plasma membrane glycoprotein.
AB  - Microtubule-associated protein (MAP) 1B is a high-molecular-weight cytoskeletal
      protein that is abundant in developing neuronal processes and appears to be
      necessary for axonal growth. Various biochemical and immunocytochemical results
      are reported, indicating that a significant fraction of MAP1B is expressed as an
      integral membrane glycoprotein in vesicles and the plasma membrane of neurons.
      MAP1B is present in microsomal fractions isolated from developing rat brain and
      fractionates across a sucrose gradient in a manner similar to synaptophysin, a
      well-known vesicular and plasma membrane protein. MAP1B is also in axolemma
      enriched fractions (AEFs) isolated from myelinated axons of rat brain. MAP1B in
      AEFs and membrane fractions from cultured dorsal root ganglion neurons (DRGNs)
      remains membrane-associated following high-salt washes and contains sialic acid.
      Furthermore, MAP1B in intact DRGNs is readily degraded by extracellular trypsin
      and is labeled by the cell surface probe sulfosuccinimidobiotin.
      Immunocytochemical examination of DRGNs shows that MAP1B is concentrated in
      vesicle-rich varicosities along the length of axons. Myelinated peripheral nerves
      immunostained for MAP1B show an enrichment at the axonal plasma membrane. These
      observations demonstrate that some of the MAP1B in developing neurons is an
      integral plasma membrane glycoprotein.

PMID- 10899929
TI  - Histamine infusion induces a selective dopaminergic neuronal death along with an
      inflammatory reaction in rat substantia nigra.
AB  - We have evaluated the effects of a direct infusion of histamine, as mediator of
      inflammatory response, in substantia nigra, striatum, medial septum, and medial
      lemniscus. Injection of 100 and 250 nmol of histamine in substantia nigra
      produced a selective damage in dopaminergic neurons evidenced by the loss of
      tyrosine hydroxylase mRNA-expressing cells, tyrosine hydroxylase-immunolabeled
      positive cell bodies, and dopamine and 3,4-dihydroxyphenylacetic acid levels. In
      parallel we found an acute inflammatory response manifested by a loss of glial
      fibrillary acidic protein-immunolabeled astrocytes and, at precisely the same
      area, an activation of microglia. In the striatum, only high doses (500 nmol)
      produced an evident terminal degeneration. The selective neurotoxicity of
      histamine for dopaminergic cells was demonstrated by the unaltered transcription
      of glutamic acid decarboxylase mRNA in substantia nigra. Moreover, intraseptal
      injection of 100 nmol of histamine failed to alter the pattern of choline
      acetyltransferase mRNA-expressing cells, and intraparenchymal injection of
      histamine in medial lemniscus failed to alter the pattern of serotonin
      immunolabeled cells. We conclude that the substantia nigra is highly sensitive to
      histamine-derived neurotoxicity, where inflammatory processes mediated by
      histamine could be important in the pathological changes that lead to
      dopaminergic neuronal damage after histamine infusion.

PMID- 10899931
TI  - Oncostatin M regulation of interleukin-6 expression in astrocytes: biphasic
      regulation involving the mitogen-activated protein kinases ERK1/2 and p38.
AB  - Oncostatin M (OSM) is a member of the interleukin (IL)-6 family of cytokines and
      has both pro- and anti-inflammatory properties. Of interest, OSM has functional
      effects within the CNS. We have shown recently that OSM can modulate expression
      of the cytokine IL-6 in astrocytes. Herein we characterize the molecular
      mechanisms and signaling cascades involved in this response. OSM induces IL-6
      protein expression in a dose- and time-dependent manner in astrocytes. In
      addition, OSM can synergize with the cytokines tumor necrosis factor-alpha, IL
      1beta, and transforming growth factor-beta for enhanced IL-6 expression. Using
      neutralizing antibodies to gp 130, the OSM receptor (OSMR), and the leukemia
      inhibitory factor receptor (LIFR), we document that OSM exclusively uses the
      OSMR/gp 130 heterodimer in signaling events, rather than the LIFR/gp 130
      heterodimer. Kinetic analysis of OSM-induced IL-6 mRNA reveals two up-regulatory
      events. The first, peaking at 1 h, is transient, does not require protein
      synthesis, and is regulated at the transcriptional level. The second, peaking
      between 6 and 8 h, is prolonged and sensitive to puromycin, suggesting a
      requirement for de novo protein synthesis, and also is transcriptionally
      regulated. OSM-induced IL-6 mRNA and protein expression is inhibited by the
      mitogen-activated protein kinase (MAPK) inhibitors U0126 and SB202190, suggesting
      a requirement for the MAPKs ERK1/2 and p38 in this response. Finally, we show
      that the MAPKs ERK1/2 and p38 are activated by OSM in astrocytes and that this
      activation is reduced by the MAPK inhibitors. These data demonstrate that OSM
      induces IL-6 expression in astrocytes and that the MAPKs ERK1/2 and p38
      participate in this response.

PMID- 10899932
TI  - Interleukin-10 and interleukin-13 inhibit proinflammatory cytokine-induced
      ceramide production through the activation of phosphatidylinositol 3-kinase.
AB  - Ceramide produced by hydrolysis of plasma membrane sphingomyelin (SM) in
      different cells including brain cells in response to proinflammatory cytokines
      [tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta)] plays an
      important role in coordinating cellular responses to stress, growth suppression,
      and apoptosis. The present study underlines the importance of IL-10 and IL-13,
      cytokines with potent antiinflammatory properties, in inhibiting the
      proinflammatory cytokine (TNF-alpha and IL-1beta)-mediated degradation of SM to
      ceramide in rat primary astrocytes. Treatment of rat primary astrocytes with TNF
      alpha or IL-1beta led to rapid degradation of SM to ceramide, whereas IL-10 and
      IL-13 by themselves were unable to induce the degradation of SM to ceramide.
      Interestingly, both IL-10 and IL-13 prevented proinflammatory cytokine-induced
      degradation of SM to ceramide. Both IL-10 and IL-13 caused rapid activation of
      phosphatidylinositol (PI) 3-kinase, and inhibition of that kinase activity by
      wortmannin and LY294002 potently blocked the inhibitory effect of IL-10 and IL-13
      on proinflammatory cytokine-mediated induction of ceramide production. This study
      suggests that the inhibition of proinflammatory cytokine-mediated degradation of
      SM to ceramide by IL-10 and IL-13 is mediated through the activation of PI 3
      kinase. As ceramide induces apoptosis and IL-10 and IL-13 inhibit the induction
      of ceramide production, we examined the effect of IL-10 and IL-13 on
      proinflammatory cytokine-mediated apoptosis. Inhibition of TNF-alpha-induced
      apoptosis by IL-10 and IL-13 suggests that the antiapoptotic nature of IL-10 and
      IL-13 is probably due to the inhibition of ceramide production.

PMID- 10899933
TI  - Aspartate mutations in presenilin and gamma-secretase inhibitors both impair
      notch1 proteolysis and nuclear translocation with relative preservation of notch1
      signaling.
AB  - It has been hypothesized that a presenilin 1 (PS1)-related enzymatic activity is
      responsible for proteolytic cleavage of the C-terminal intracellular protein of
      Notch1, in addition to its role in beta-amyloid protein (Abeta) formation from
      the amyloid precursor protein (APP). We developed an assay to monitor ligand
      induced Notch1 proteolysis and nuclear translocation in individual cells :
      Treatment of full-length Notch1-enhanced green fluorescent protein-transfected
      Chinese hamster ovary (CHO) cells with a soluble preclustered form of the
      physiologic ligand Delta leads to rapid accumulation of the C terminus of Notch1
      in the nucleus and to transcriptional activation of a C-promoter binding factor 1
      (CBF1) reporter construct. Nuclear translocation was blocked by cotransfection
      with Notch's physiologic inhibitor Numb. Using this assay, we now confirm and
      extend the observation that PS1 is involved in Notch1 nuclear translocation and
      signaling in mammalian cells. We demonstrate that the D257A and the D385A PS1
      mutations, which had been shown previously to block APP gamma-secretase activity,
      also prevent Notch1 cleavage and translocation to the nucleus but do not alter
      Notch1 trafficking to the cell surface. We also show that two APP gamma-secretase
      inhibitors block Notch1 nuclear translocation with an IC(50) similar to that
      reported for APP gamma-secretase. Notch1 signaling, assessed by measuring the
      activity of CBF1, a downstream transcription factor, was impaired but not
      abolished by the PS1 aspartate mutations or gamma-secretase inhibitors. Our
      results support the hypotheses that (a) PS1-dependent APP gamma-secretase-like
      enzymatic activity is critical for both APP and Notch processing and (b) the
      Notch1 signaling pathway remains partially activated even when Notch1 proteolytic
      processing and nuclear translocation are markedly inhibited. The latter is an
      important finding from the perspective of therapeutic treatment of Alzheimer's
      disease by targeting gamma-secretase processing of APP to reduce Abeta
      production.

PMID- 10899934
TI  - Modulation of the phosphorylation and activity of calcium/calmodulin-dependent
      protein kinase II by zinc.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMPK-II) is a key regulatory
      enzyme in living cells. Modulation of its activity, therefore, could have a major
      impact on many cellular processes. We found that Zn(2+) has multiple functional
      effects on CaMPK-II. Zn(2+) generated a Ca(2+)/CaM-independent activity that
      correlated with the autophosphorylation of Thr(286), inhibited Ca(2+)/CaM binding
      that correlated with the autophosphorylation of Thr(306), and inhibited CaMPK-II
      activity at high concentrations that correlated with the autophosphorylation of
      Ser(279). The relative level of autophosphorylation of these three sites was
      dependent on the concentration of zinc used. The autophosphorylation of at least
      these three sites, together with Zn(2+) binding, generated an increased mobility
      form of CaMPK-II on sodium dodecyl sulfate gels. Overall, autophosphorylation
      induced by Zn(2+) converts CaMPK-II into a different form than the binding of
      Ca(2+)/CaM. In certain nerve terminals, where Zn(2+) has been shown to play a
      neuromodulatory role and is present in high concentrations, Zn(2+) may turn CaMPK
      II into a form that would be unable to respond to calcium signals.

PMID- 10899935
TI  - Calcineurin activity is regulated both by redox compounds and by mutant familial
      amyotrophic lateral sclerosis-superoxide dismutase.
AB  - Calcineurin (CN) is a protein phosphatase involved in a wide range of cellular
      responses to calcium-mobilizing signals, and a role for this enzyme in
      neuropathology has been postulated. We have investigated the possibility that
      redox modulation of CN activity is relevant to neuropathological conditions where
      an imbalance in reactive oxygen species has been described. We have monitored CN
      activity in cultured human neuroblastoma SH-SY5Y cells and obtained evidence that
      CN activity is promoted by treatment with ascorbate or dithiothreitol and
      impaired by oxidative stress. Evidence for the existence of a redox regulation of
      this enzyme has been also obtained by overexpression of wild-type antioxidant
      Cu,Zn superoxide dismutase (SOD1) that promotes CN activity and protects it from
      oxidative inactivation. On the contrary, overexpression of mutant SOD1s
      associated with familial amyotrophic lateral sclerosis (FALS) impairs CN activity
      both in transfected human neuroblastoma cell lines and in the motor cortex of
      brain from FALS-transgenic mice. These data suggest that CN might be a target in
      the pathogenesis of SOD1-linked FALS.

PMID- 10899936
TI  - Induction of cyclooxygenase-2 by overexpression of the human catalase gene in
      cerebral microvascular endothelial cells.
AB  - Prostaglandin (PG) formation by the inducible (type 2) cyclooxygenase (COX-2) and
      reactive oxygen species (ROS) have been proposed to play important roles in
      cerebrovascular pathological processes. To explore the relationship between ROS
      and COX-2 expression, adenovirus (Ad) vectors containing cDNA for human
      antioxidant enzymes including catalase (AdCAT:), copper/zinc superoxide dismutase
      (AdCu/ZnSOD), and manganese superoxide dismutase (AdMnSOD) were transferred into
      murine cerebral microvascular endothelial cells. AdCAT: (100 multiplicity of
      infection) infection increased the content and enzymatic activity of cellular Cat
      threefold and decreased the intracellular peroxide level. The expression of COX-2
      mRNA and protein in cell lysates was up-regulated, and the amount of PGE(2)
      formed from exogenous arachidonic acid increased following AdCAT: infection in a
      dose-dependent manner, paralleling the expression of COX-2 protein. The AdCAT:
      induced increase in PGE(2) formation was inhibited by NS-398, a selective
      inhibitor of COX-2 enzymatic activity. AdCAT: infection did not change the
      expression of the constitutive (type 1) COX protein. Although AdCu/ZnSOD and
      AdMnSOD infection increased the expression of superoxide dismutase proteins, COX
      2 expression was not induced. An in vitro nuclear transcription assay indicated
      that overexpression of the Cat gene increases the transcription of the COX-2
      gene. Furthermore, the stability of COX-2 mRNA induced by lipopolysaccharide was
      increased after AdCAT: gene transfer. These results indicate that AdCAT: gene
      transfer induces the transcriptional activation of the COX-2 gene and increases
      COX-2 mRNA stability. Therefore, peroxide may have regulatory effect on COX-2
      function in the cerebral microcirculation.

PMID- 10899937
TI  - The neuronal microtubule-associated protein tau is a substrate for caspase-3 and
      an effector of apoptosis.
AB  - We have identified a class of tau fragments inducing apoptosis in different
      cellular contexts, including a human teratocarcinoma-derived cell line (NT2
      cells) representing committed human neuronal precursors. We have found a
      transition point inside the tau molecule beyond which the fragments lose their
      ability to induce apoptosis. This transition point is located around one of the
      putative caspase-3 cleavage sites. This is the only site that can be effectively
      used by caspase-3 in vitro, releasing the C-terminal 19 amino acids of tau. These
      results establish tau as a substrate for an apoptotic protease that turns tau
      itself into an effector of apoptosis. Accordingly, tau may be involved in a self
      propagating process like what has been predicted for the pathogenesis of
      different neurodegenerative disorders.

PMID- 10899938
TI  - The inhibitory effects of interleukin-6 on synaptic plasticity in the rat
      hippocampus are associated with an inhibition of mitogen-activated protein kinase
      ERK.
AB  - Several cytokines have short-term effects on synaptic transmission and plasticity
      that are thought to be mediated by the activation of intracellular protein
      kinases. We have studied the effects of interleukin-6 (IL-6) on the expression of
      paired pulse facilitation (PPF), posttetanic potentiation (PTP), and long-term
      potentiation (LTP) in the CA1 region of the hippocampus as well as on the
      activation of the signal transducer and activator of transcription-3 (STAT3), the
      mitogen-activated protein kinase ERK (MAPK/ERK), and the stress-activated protein
      kinase/c-Jun NH(2)-terminal kinase (SAPK/JNK). IL-6 induced a marked and dose
      dependent decrease in the expression of PTP and LTP that could be counteracted by
      the simultaneous treatment with the tyrosine kinase inhibitor lavendustin A
      (LavA) but did not significantly affect PPF. The IL-6-induced inhibition of PTP
      and LTP was accompanied by a simulation of STAT3 tyrosine phosphorylation and an
      inhibition of MAPK/ERK dual phosphorylation, in the absence of changes in the
      state of activation of SAPK/JNK. Both effects of IL-6 on STAT3 and MAPK/ERK
      activation were effectively counteracted by LavA treatment. The results indicate
      the tyrosine kinases and MAPK/ERK are involved in hippocampal synaptic plasticity
      and may represent preferential intracellular targets for the actions of IL-6 in
      the adult nervous system.

PMID- 10899939
TI  - Binding of the GABA(A) receptor-associated protein (GABARAP) to microtubules and
      microfilaments suggests involvement of the cytoskeleton in GABARAPGABA(A)
      receptor interaction.
AB  - GABA(A) receptor-associated protein (GABARAP) was isolated on the basis of its
      interaction with the gamma2 subunit of GABA(A) receptors. It has sequence
      similarity to light chain 3 (LC3) of microtubule-associated proteins 1A and 1B.
      This suggests that GABARAP may link GABA(A) receptors to the cytoskeleton.
      GABARAP associates with tubulin in vitro. However, little is known about the
      mechanism for the interaction, and it is not clear whether the interaction occurs
      in vivo. Here, we report that GABARAP interacts directly with both tubulin and
      microtubules in a salt-sensitive manner, indicating the association is mediated
      by ionic interactions. GABARAP coimmunoprecipitates with tubulin and associates
      with both microtubules and microfilaments in intact cells. The cellular
      distribution is altered by treatment with taxol, nocodazole, and cytochalasin D.
      The tubulin binding domain was located at the N terminus of GABARAP by using
      synthetic peptides and deletion constructs and is marked by a specific
      arrangement of basic amino acids. The interaction between GABARAP and actin might
      be mediated by other proteins. These results demonstrate the GABARAP interacts
      with the cytoskeleton both in vitro and in cells and suggest a role of GABARAP in
      the interaction between GABA(A) receptors and the cytoskeleton. Such interactions
      are presumably needed for receptor trafficking, anchoring, and/or synaptic
      clustering. The structural arrangement of the basic amino acids present in the
      tubulin binding domain of GABARAP may aid in recognition of the potential of
      tubulin binding activity in other known proteins.

PMID- 10899940
TI  - Adenosine A(1) receptor in cultured neurons from rat cerebral cortex:
      colocalization with adenosine deaminase.
AB  - Adenosine A(1) receptors (A(1)Rs) have been characterized in primary cultures of
      neurons from cerebral cortex. The specific adenosine A(1) antagonist 8
      cyclopentyl-1,3-[(3)H]dipropylxanthine bound to both membranes and intact cells.
      When saturation experiments were performed in membranes, a K(D) value of 0.76 nM
      and a B(max) of 57 fmol/mg of protein were obtained. Competition assays revealed
      a pharmacological profile characteristic of A(1)Rs. The presence of this receptor
      was further confirmed by RT-PCR analysis. The expression of the receptor showed
      no significant changes during the period of culture studied, up to 12 days in
      vitro. A(1)R agonist inhibited forskolin-stimulated adenylyl cyclase, showing the
      functional coupling of these receptors with the effector. alphaG(i1, 2) protein
      level, detected by immunoblot, presented an increase during the period of
      culture. This increase correlated with an increase in the mRNA level of
      alphaG(i1) but not alphaG(i2). By immunochemical assays, it is shown that these
      receptors are expressed in both the neuronal cell body and the proximal
      dendrites. Colocalization of A(1)Rs with microtubule-associated protein 2 and
      cell surface adenosine deaminase was shown by confocal microscopy. The high
      degree of colocalization observed between A(1)Rs and ectoadenosine deaminase in
      neurons could suggest an important role of the enzyme in adenosine-mediated
      neuromodulation.

PMID- 10899941
TI  - Neurite outgrowth induced by a synthetic peptide ligand of neural cell adhesion
      molecule requires fibroblast growth factor receptor activation.
AB  - The neural cell adhesion molecule NCAM is involved in axonal outgrowth and target
      recognition in the developing nervous system. In vitro, NCAM-NCAM binding has
      been shown to induce neurite outgrowth, presumably through an activation of
      fibroblast growth factor receptors (FGFRs). We have recently identified a
      neuritogenic ligand, termed the C3 peptide, of the first immunoglobulin (lg)
      module of NCAM using a combinatorial library of synthetic peptides. Here we
      investigate whether stimulation of neurite outgrowth by this synthetic ligand of
      NCAM involves FGFRs. In primary cultures of cerebellar neurons from wild-type
      mice, the C3 peptide stimulated neurite outgrowth. This response was virtually
      absent in cultures of cerebellar neurons from transgenic mice expressing a
      dominant-negative form of the FGFR1. Likewise, in PC12E2 cells transiently
      expressing a dominant-negative form of the mouse FGFR1, induction of neurites by
      the C3 peptide was abrogated. These findings suggest that the neuritogenic effect
      of the C3 peptide requires the presence of functional FGFRs and support the
      hypothesis that FGFRs are essential in cell adhesion molecule-stimulated neurite
      outgrowth. The C3 peptide appears to stimulate neurite outgrowth by specifically
      activating an NCAM-FGFR-dependent signaling cascade and may therefore be of
      considerable interest as a tool for the determination of NCAM-dependent neurite
      outgrowth as well as a potential drug capable of promoting outgrowth and
      regeneration of NCAM-responsive axons.

PMID- 10899942
TI  - Up-regulation of cell surface insulin receptor by protein kinase C-alpha in
      adrenal chromaffin cells: involvement of transcriptional and translational
      events.
AB  - Our previous study showed that treatment of cultured bovine adrenal chromaffin
      cells with phorbol 12, 13-dibutyrate (PDBu) or 12-O-tetradecanoylphorbol 13
      acetate (TPA) caused a rapid (<15 min) and persistent (>15 h) translocation of
      both conventional (c) protein kinase C-alpha (PKC-alpha) and novel PKC-epsilon
      (but not atypical PKC-zeta) from cytosol to membranes, whereas thymeleatoxin
      (TMX) increased the similar but selective membrane association of only cPKC
      alpha. In the present study, chronic (>/=12 h) treatment of chromaffin cells with
      PDBu raised cell surface (125)I-insulin binding without altering the K(D) value;
      it developed in a concentration (EC(50) = 1.9 nM)-and time (t(1/2) = 14.6 h)
      dependent manner, reaching its maximum 115% increase at 48 h. Either TPA (30 nM)
      or TMX (EC(50) = 6.4 nM) also increased (125)I-insulin binding by 97 or 88%,
      whereas the biologically inactive 4alpha-TPA had no effect. The increasing effect
      of PDBu (30 nM for 24 h) on (125)I-insulin binding was significantly blocked,
      even when H7, an inhibitor of PKC, was added at 8 h after the initiation of PDBu
      treatment. Concurrent treatment with brefeldin A, an inhibitor of vesicular
      transport from the trans-Golgi network, cycloheximide, an inhibitor of protein
      synthesis, or 5,6-dichlorobenzimidazole riboside, an inhibitor of RNA synthesis,
      abolished the PDBu-induced increment of (125)I-insulin binding. Western blot
      analysis, using antibody against the beta-subunit of the insulin receptor, showed
      that treatment with PDBu (30 nM) or TMX (EC(50) = 2.3 nM) increased levels of
      insulin receptor precursor (approximately 190 kDa; t(1/2) = 7.1 h) and insulin
      receptor beta-subunit (t(1/2) = 15.4 h), causing their almost maximum 52 and 59%
      rises, respectively, at 24 h. Northern blot analysis revealed that PDBu or TMX
      increased levels of insulin receptor mRNAs by approximately 35% as soon as 3 h,
      producing its monophasic peak approximately 76% increases at 24 h. All of these
      increasing effects of PDBu and TMX on (125)I-insulin binding and insulin receptor
      beta-subunit and insulin receptor mRNA levels were entirely prevented by
      simultaneous treatment with Go6976, a selective inhibitor of cPKC. These results
      suggest that long-term activation of cPKC-alpha up-regulates the density of the
      cell surface insulin receptor via transcriptional/translational events.

PMID- 10899943
TI  - A pathway of neuronal apoptosis induced by hypoxia/reoxygenation: roles of
      nuclear factor-kappaB and Bcl-2.
AB  - As a model of the reperfusion injury found in stroke, we have exposed neurons to
      hypoxia followed by reoxygenation. Neurons treated with hypoxia/reoxygenation
      (H/R) respond by activating nuclear factor-kappaB (NFkappaB), releasing
      cytochrome c from their mitochondria, and ultimately dying. Further supporting an
      apoptotic mechanism, expression of the antiapoptotic Bcl-2 and Bcl-x proteins was
      increased following H/R. In this model, adenoviral-mediated transduction of
      lkappaB expression inhibited NFkappaB activation and significantly accelerated
      cytochrome c release and caspase-dependent neuronal death. At the same time,
      expression of mutated lkappaB prevented the increased expression of endogenous
      Bcl-2 and Bcl-x. In the presence of mutated lkappaB, singular overexpression of
      only Bcl-2 by adenoviral-mediated transduction significantly inhibited cytochrome
      c release, caspase-3-like activation, and cell death in response to H/R. These
      findings suggest a pathway where NFkappaB activation induces overexpression of
      Bcl-2 and Bcl-x, which function to prevent apoptotic cell death following H/R
      treatments.

PMID- 10899944
TI  - Astrocyte-derived nitric oxide causes both reversible and irreversible damage to
      the neuronal mitochondrial respiratory chain.
AB  - Cytokine-stimulated astrocytes produce nitric oxide (NO), which, along with its
      metabolite peroxynitrite (ONOO(-)), can inhibit components of the mitochondrial
      respiratory chain. We used astrocytes as a source of NO/ONOO(-) and monitored the
      effects on neurons in coculture. We previously demonstrated that astrocytic
      NO/ONOO(-) causes significant damage to the activities of complexes II/III and IV
      of neighbouring neurons after a 24-h coculture. Under these conditions, no
      neuronal death was observed. Using polytetrafluoroethane filters, which are
      permeable to gases such as NO but impermeable to NO derivatives, we have now
      demonstrated that astrocyte-derived NO is responsible for the damage observed in
      our coculture system. Expanding on these observations, we have now shown that 24
      h after removal of NO-producing astrocytes, neurons exhibit complete recovery of
      complex II/III and IV activities. Furthermore, extending the period of exposure
      of neurons to NO-producing astrocytes does not cause further damage to the
      neuronal mitochondrial respiratory chain. However, whereas the activity of
      complex II/III recovers with time, the damage to complex IV caused by a 48-h
      coculture with NO-producing astrocytes is irreversible. Therefore, it appears
      that neurons can recover from short-term damage to mitochondrial complex II/III
      and IV, whereas exposure to astrocytic-derived NO for longer periods causes
      permanent damage to neuronal complex IV.

PMID- 10899945
TI  - The triakontatetraneuropeptide (TTN) stimulates thymidine incorporation in rat
      astrocytes through peripheral-type benzodiazepine receptors.
AB  - Astrocytes and astrocytoma cells actively express the diazepam-binding inhibitor
      (DBI) gene, suggesting that DBI-processing products may regulate glial cell
      activity. In the present study, we have investigated the possible effect of one
      of the DBI-derived peptides, the triakontatetraneuropeptide (TTN), on
      [(3)H]thymidine incorporation in cultured rat astrocytes. Reversed-phase HPLC
      analysis of incubation media indicated that TTN is the major form of DBI-derived
      peptides released by cultured astrocytes. At very low concentrations (10(-14)-10(
      11) M), TTN induced a dose-dependent increase in [(3)H]thymidine incorporation,
      whereas at higher concentrations (10(-10)-10(-5) M) the effect of TTN gradually
      declined. In the same range of concentrations, the specific peripheral-type
      benzodiazepine receptor (PBR) agonist Ro 5-4864 mimicked the bell-shaped
      stimulatory effect of TTN on [(3)H]thymidine incorporation. The PBR antagonist
      PK11195 (10(-6) M) suppressed the stimulatory action of both TTN and Ro 5-4864 on
      [(3)H]thymidine incorporation, whereas the central-type benzodiazepine receptor
      antagonist flumazenil (10(-6) M) had no effect. The present study demonstrates
      that the endozepine TTN stimulates DNA synthesis in rat glial cells through
      activation of PBRs. These data strongly suggest that TTN exerts an
      autocrine/paracrine stimulatory effect on glial cell proliferation.

PMID- 10899947
TI  - Identification of a histamine H(3)-like receptor in the zebrafish (Danio rerio)
      brain.
AB  - The distribution of histaminergic fibers in the zebrafish brain was recently
      shown to resemble that in mammals. Expression of L-histidine decarboxylase (HDC)
      mRNA was shown only in the area corresponding to that expressing HDC in mammals.
      This indicates that the zebrafish could be a useful model for studies on the
      function of the brain histaminergic system. In this study an H(3)-like receptor
      is identified in zebrafish brain. With binding studies using N-alpha
      [(3)H]methylhistamine on zebrafish brain sections, signals were observed in
      several regions. Highest densities were detected in optic tectum and
      hypothalamus. The autoradiographic signal was abolished completely by the H(3)
      specific antagonist clobenpropit and significantly reduced by another H(3)
      antagonist, thioperamide. Histamine and immepip induced an increase of guanosine
      5'-(gamma-[(35)S]thio)triphosphate binding in several areas of the zebrafish
      brain. The activation was blocked with clobenpropit but not with cimetidine or
      mepyramine. These results indicate that the zebrafish has a histamine H(3)-like
      receptor that functionally interacts with the inhibitory, G(i)/G(o), class of G
      proteins. No previous evidence for a histamine receptor in zebrafish exists. The
      receptor described here is apparently similar to the mammalian H(3) receptor,
      making this the first description of a histamine H(3)-like receptor in a lower
      vertebrate.

PMID- 10899946
TI  - Galpha(12) and galpha(13) inhibit Ca(2+)-dependent exocytosis through Rho/Rho
      associated kinase-dependent pathway.
AB  - The release of neurotransmitters is known to be regulated by activation of
      heterotrimeric G protein-coupled receptors, although precise mechanisms have not
      yet been elucidated. To assess the role of the G(12) family of heterotrimeric G
      proteins in the regulation of neurotransmitter release, we established PC12 cell
      lines that expressed constitutively active Galpha(12) or Galpha(13) using an
      isopropyl-beta-D-thiogalactoside-inducible expression system. In the cells,
      expression of constitutively active Galpha(12) or Galpha(13) inhibited the high
      K(+)-evoked [(3)H]dopamine release without any effect on the high K(+)-induced
      increase in intracellular Ca(2+) concentration. A Ca(2+) ionophore ionomycin
      induced [(3)H]dopamine release was also inhibited by the expression of active
      Galpha(12) or Galpha(13). These inhibitory effects of Galpha(12) and Galpha(13)
      on [(3)H]dopamine release were mimicked by the expression of constitutively
      active RhoA. In addition, Y-27632, and inhibitor of Rho-associated kinase, a
      downstream Rho effector, completely abolished the inhibition of [(3)H]dopamine
      release by Galpha(12), Galpha(13), and RhoA. These results indicate that Ca(2+)
      dependent exocytosis is regulated by Galpha(12) and Galpha(13) through a Rho/Rho
      associated kinase-dependent pathway.

PMID- 10899948
TI  - Phosphorylation and activation of brain aromatic L-amino acid decarboxylase by
      cyclic AMP-dependent protein kinase.
AB  - Aromatic L-amino acid decarboxylase (AAAD), an enzyme required for the synthesis
      of catecholamines, indoleamines, and trace amines, is rapidly activated by cyclic
      AMP-dependent pathways in striatum and midbrain in vivo, suggesting enzyme
      phosphorylation. We now report that the catalytic subunit of cyclic AMP-dependent
      protein kinase (PKA) directly phosphorylated AAAD immunoprecipitated from
      homogenates prepared from the mouse striatum and midbrain in vitro. Under the
      same phosphorylation conditions, the catalytic subunit of PKA also phosphorylated
      a recombinant AAAD protein expressed in Escherichia coli transfected with an AAAD
      cDNA isolated from the bovine adrenal gland. The PKA-induced AAAD phosphorylation
      of immunoprecipitates from striatum and midbrain was time and concentration
      dependent and blocked by a specific PKA peptide inhibitor. Incubation of the
      catalytic subunit of PKA with striatal homogenates increased enzyme activity by
      approximately 20% in a time- and concentration-dependent manner. Moreover,
      incubation of the catalytic subunit of PKA with recombinant AAAD increased
      activity by approximately 70%. A direct phosphorylation of AAAD protein by PKA
      might underlie the cyclic AMP-induced rapid and transient activation of AAAD in
      vivo.

PMID- 10899949
TI  - Social isolation-induced decreases in both the abundance of neuroactive steroids
      and GABA(A) receptor function in rat brain.
AB  - The effects of social isolation on behavior, neuroactive steroid concentrations,
      and GABA(A) receptor function were investigated in rats. Animals isolated for 30
      days immediately after weaning exhibited an anxiety-like behavioral profile in
      the elevated plus-maze and Vogel conflict tests. This behavior was associated
      with marked decreases in the cerebrocortical, hippocampal, and plasma
      concentrations of pregnenolone, progesterone, allopregnanolone, and
      allotetrahydrodeoxycorticosterone compared with those apparent for group-housed
      rats; in contrast, the plasma concentration of corticosterone was increased in
      the isolated animals. Acute footshock stress induced greater percentage increases
      in the cortical concentrations of neuroactive steroids in isolated rats than in
      group-housed rats. Social isolation also reduced brain GABA(A) receptor function,
      as evaluated by measuring both GABA-evoked Cl(-) currents in Xenopus oocytes
      expressing the rat receptors and tert-[(35)S]butylbicyclophosphorothionate
      ([(35)S]TBPS) binding to rat brain membranes. Whereas the amplitude of GABA
      induced Cl(-) currents did not differ significantly between group-housed and
      isolated animals, the potentiation of these currents by diazepam was reduced at
      cortical or hippocampal GABA(A) receptors from isolated rats compared with that
      apparent at receptors from group-housed animals. Moreover, the inhibitory effect
      of ethyl-beta-carboline-3-carboxylate, a negative allosteric modulator of GABA(A)
      receptors, on these currents was greater at cortical GABA(A) receptors from
      socially isolated animals than at those from group-housed rats. Finally, social
      isolation increased the extent of [(35)S]TBPS binding to both cortical and
      hippocampal membranes. The results further suggest a psychological role for
      neurosteroids and GABA(A) receptors in the modulation of emotional behavior and
      mood.

PMID- 10899950
TI  - Chronic morphine treatment and withdrawal increase extracellular levels of
      norepinephrine in the rat bed nucleus of the stria terminalis.
AB  - Extracellular levels of norepinephrine (NE) and glutamate (Glu) in the ventral
      bed nucleus of the stria terminalis (vBNST) of saline- and chronic morphine
      treated rats, with or without withdrawal, were studied by means of the in vivo
      microdialysis technique in anesthetized rats. In addition, the tissue
      concentration of NE was studied at different rostrocaudal levels of the vBNST.
      Chronic morphine treatment significantly increased extracellular levels of NE,
      but not Glu, in vBNST. At 48 h after naloxone-induced morphine withdrawal there
      was a further significant increase in the extracellular levels of NE, but not
      Glu, in vBNST. The presence of UK 14304, an alpha(2)-adrenergic agonist, induced
      a significant decrease in NE extracellular levels in all experimental groups. In
      contrast, UK 14304 induced a significant decrease in Glu extracellular levels
      only in saline-treated rats. The results also show that the vBNST presents a
      rostrocaudal gradient of NE and contains 9.4% of total brain NE. The increase in
      NE extracellular levels in vBNST induced by chronic morphine treatment and the
      further increase in NE levels 48 h after naloxone-induced morphine withdrawal
      suggest that NE in vBNST may be involved in the pharmacological effects of
      chronic morphine and withdrawal.

PMID- 10899951
TI  - Modulation of hypothalamic NMDA receptor function by cyclic AMP-dependent protein
      kinase and phosphatases.
AB  - In the present study we investigated the modulation of hypothalamic NMDA receptor
      mediated currents by cyclic AMP-dependent protein kinase (PKA) using the two
      electrode voltage-clamp technique in Xenopus oocytes injected with rat
      hypothalamic mRNA. Application of forskolin, which activates PKA by means of
      cyclic AMP stimulation, caused a transient increase of NMDA-induced currents,
      whereas the inactive forskolin analogue 1,9-dideoxyforskolin had no effect.
      Incubation of oocytes with a membrane-permeable analogue of cyclic AMP, 8
      bromoadenosine 3',5' -cyclic monophosphate, potentiated NMDA responses even more
      prominently than with forskolin. NMDA-induced currents recorded from Xenopus
      oocytes injected with cRNA encoding the NMDA receptor subunits NR1, NR2A, and/or
      NR2B, mainly found in rat hypothalamus, were not affected by PKA activation but
      were increased by protein kinase C (PKC) stimulation. It is interesting that
      inhibition of endogenous protein phosphatase 1 and/or 2A by calyculin A resulted
      in a similar enhancement of hypothalamic NMDA-induced currents. Preinjection of
      oocytes with calyculin A impeded the PKA- but not the PKC-mediated potentiation
      of hypothalamic NMDA-induced currents. We propose the involvement of an
      additional third messenger in the PKA effect, which acts most likely via the
      inhibition of tonically active protein phosphatase 1 and/or 2A.

PMID- 10899953
TI  - Calmodulin regulation of basal and agonist-stimulated G protein coupling by the
      mu-opioid receptor (OP(3)) in morphine-pretreated cell.
AB  - Calmodulin (CaM) has been shown to suppress basal G protein coupling and
      attenuate agonist-stimulated G protein coupling of the mu-opioid receptor (OP(3))
      through direct interaction with the third intracellular (i3) loop of the
      receptor. Here we have investigated the role of CaM in regulating changes in
      OP(3)-G protein coupling during morphine treatment, shown to result in CaM
      release from plasma membranes. Basal and agonist-stimulated G protein coupling by
      OP(3) was measured before and after morphine pretreatment by incorporation of
      guanosine 5'-O-(3-[(35)S]thiotriphosphate) into membranes, obtained from HEK 293
      cells transfected with human OP(3) cDNA. The opioid antagonist beta
      chlornaltrexamine fully suppressed basal G protein coupling of OP(3), providing a
      direct measure of basal signaling. Pretreatment of the cells with morphine
      enhanced basal G protein coupling (sensitization). In contrast, agonist
      stimulated coupling was diminished (desensitization), resulting in a
      substantially flattened morphine dose-response curve. To test whether CaM is
      involved in these changes, we constructed OP(3)-i3 loop mutants with reduced
      affinity for CaM (K273A, R275A, and K273A/R275A). Basal signaling of these mutant
      OP(3) receptors was higher than that of the wild-type receptor and, moreover,
      unaffected by morphine pretreatment, whereas desensitization to agonist
      stimulation was only slightly attenuated. Therefore, CaM-OP(3) interactions
      appear to play only a minor role in the desensitization of OP(3). In contrast,
      release of CaM from the plasma membrane appears to enhance the inherent basal G
      protein coupling of OP(3), thereby resolving the paradox that OP(3) displays both
      desensitization and sensitization during morphine treatment.

PMID- 10899952
TI  - Affinity of (+/-)-pindolol, (-)-penbutolol, and (-)-tertatolol for pre- and
      postsynaptic serotonin 5-HT(1A) receptors in human and rat brain.
AB  - There is considerable interest in the use of drugs that selectively block
      presynaptic (somatodendritic) serotonin 5-HT(1A) receptors for the adjunctive
      treatment of major depressive disorder. The 5-HT(1A)/beta-adrenoceptor ligands
      (+/-)-pindolol, (-)-tertatolol, and (-)-penbutolol are currently under clinical
      investigation, and knowledge of their affinity at different populations of
      central 5-HT(1A) receptors is needed. Here we have determined the affinity of
      these drugs for presynaptic and postsynaptic 5-HT(1A) receptors in postmortem
      human and rat brain using receptor autoradiography and the selective 5-HT(1A)
      radioligand [(3)H]WAY-100635. The binding of [(3)H]WAY-100635 was specific and
      saturable and showed high affinity in the rat dorsal raphe nucleus and
      hippocampus (K(D) = 1.5-1.7 nM). In competition studies, the three compounds had
      nanomolar affinity and produced monophasic displacement of [(3)H]WAY-100635
      binding in all regions of both species. (-)-Penbutolol and (-)-tertatolol had
      similar affinity for pre-and postsynaptic 5-HT(1A) receptors in both rat and
      human brain. However, in the human, but not the rat, the affinity of (+/-)
      pindolol in dorsal raphe nucleus (K(i) = 8.9 +/- 1. 1 nM) was slightly but
      significantly higher than that in hippocampus (K(i) = 14.4 +/- 1.5 nM in CA1). In
      summary, our data show that (+/-)-pindolol, (-)-tertatolol, and (-)-penbutolol
      are all high-affinity ligands at native human and rat 5-HT(1A) receptors. (-)
      Penbutolol and (-)-tertatolol do not discriminate between the pre- and
      postsynaptic 5-HT(1A) sites tested in either species, but (+/-)-pindolol showed a
      slightly higher affinity for the presynaptic site in human brain. Further work is
      needed to establish whether the latter difference is clinically relevant.

PMID- 10899954
TI  - Ca(2+)/calmodulin-mediated regulation of the desensitizing process in G(q)
      protein-coupled histamine H(1) receptor-mediated Ca(2+) responses in human U373
      MG astrocytoma cells.
AB  - We investigated Ca(2+)/calmodulin (CaM)-mediated regulation of the desensitizing
      process of the histamine H(1) receptor-mediated increase in intracellular Ca(2+)
      concentration in human U373 MG astrocytoma cells. The desensitizing process was
      evaluated by measuring the histamine-induced Ca(2+) responses in cells pretreated
      with histamine for 15 s-30 min under various conditions. Under normal
      physiological conditions, desensitization developed with three successive phases
      : a fast desensitization within 15 s, a transient resensitization at 45 s, and a
      prompt and sustained redesensitization from 1 to 30 min. Similar processes of
      desensitization/resensitization occurred even under hypertonic conditions, where
      histamine-mediated internalization of the histamine H(1) receptor is inhibited.
      The transient resensitization phase was selectively prevented by deprivation of
      extracellular Ca(2+) and, even more strikingly, by the presence of W-7 (a CaM
      antagonist). FK506 and cyclosporin A, Ca(2+)/CaM-dependent protein phosphatase
      (PP2B) inhibitors, mimicked such effects. In the presence of KN-62, a Ca(2+)/CaM
      dependent protein kinase II (CaM kinase II) inhibitor, the early development of
      desensitization disappeared, allowing a slow and simple development of
      desensitization. The early processes of desensitization and resensitization were
      unaffected by W-5, okadaic acid, and KN-04 (less potent inhibitors against CaM,
      PP2B, and CaM kinase II, respectively) or by GF109203X and chelerythrine (protein
      kinase C inhibitors). The high-affinity site for histamine was converted to a
      lower-affinity site by histamine treatment, which also showed a transient
      restoration phase at 45 s in a manner sensitive to KN-62 and FK506. These results
      provide the first evidence that Ca(2+)/CaM plays a crucial role in determining
      the early phase of the desensitizing process via activation of CaM kinase II and
      PP2B, by regulating agonist affinity for histamine H(1) receptors.

PMID- 10899955
TI  - Benzodiazepine-sensitive GABA(A) receptors limit the activity of the
      NMDA/NO/cyclic GMP pathway: a microdialysis study in the cerebellum of freely
      moving rats.
AB  - In the cerebellum, infusion of NMDA (200 microM) for 20 min evoked a marked
      (200%) increase of extracellular cyclic GMP (cGMP) levels. The selective GABA(A)
      receptor agonist muscimol (0.01-100 microM) was able to counteract the NMDA
      effect with an EC(50) of 0.65 microM; the inhibitory effect of muscimol (10
      microM) was prevented by bicuculline (50 microM). Diazepam (10 microM)
      significantly potentiated the muscimol (1 microM) inhibition; furthermore, when
      coinfused with 0.1 microM muscimol (a concentration not affecting, on its own,
      the cGMP response to NMDA), diazepam (10 microM) reduced the NMDA effect. Similar
      results were obtained with zolpidem (0.1-1 microM). Finally, local infusion of
      the benzodiazepine site antagonist flumazenil (10 microM), together with muscimol
      and diazepam, almost completely restored the effect of NMDA on extracellular cGMP
      levels. It is concluded that GABA(A) receptors potently control the NMDA/nitric
      oxide/cGMP pathway in the cerebellum in vivo. In terms of the alpha subunit
      composition, we can deduce that the cerebellar GABA(A) receptor does not contain
      alpha(6) or beta(4) subunits because it is diazepam-sensitive. Moreover, the
      observation that zolpidem is active at a rather low concentration, in combination
      with localization studies present in the literature, tend to exclude the presence
      of alpha(5) subunits in the receptor composition and suggest the involvement of
      an alpha(1) subunit.

PMID- 10899956
TI  - Effects of oxidative stress on phospholipid signaling in rat cultured astrocytes
      and brain slices.
AB  - Although reactive oxygen species (ROS) are conventionally viewed as toxic by
      products of cellular metabolism, a growing body of evidence suggests that they
      may act as signaling molecules. We have studied the effects of hydrogen peroxide
      (H(2)O(2))-induced oxidative stress on phospholipid signaling in cultured rat
      cortical astrocytes. H(2)O(2) stimulated the formation of phosphatidic acid and
      the accumulation of phosphatidylbutanol, a product of the phospholipase D (PLD)
      catalyzed transphosphatidylation reaction. The effect of exogenous H(2)O(2) on
      the PLD response was mimicked by menadione-induced production of endogenous
      H(2)O(2). Oxidative stress also elicited inositol phosphate accumulation
      resulting from phosphoinositide phospholipase C (PLC) activation. The PLD
      response to H(2)O(2) was totally suppressed by chelation of both extracellular
      and cytosolic Ca(2+) with EGTA and BAPTA/AM, respectively. Furthermore, H(2)O(2)
      induced PLD stimulation was completely abolished by the protein kinase C (PKC)
      inhibitors bisindolylmaleimide and chelerythrine and by PKC down-regulation.
      Activation of PLD by H(2)O(2) was also inhibited by the protein-tyrosine kinase
      inhibitor genistein. Finally, H(2)O(2) also stimulated both PLC and PLD in rat
      brain cortical slices. These results show for the first time that oxidative
      stress elicits phospholipid breakdown by both PLC and PLD in rat cultured
      astrocytes and brain slices.

PMID- 10899957
TI  - Effects of nitrobenzylthioinosine on neuronal injury, adenosine levels, and
      adenosine receptor activity in rat forebrain ischemia.
AB  - Adenosine levels increase in brain during cerebral ischemia, and adenosine has
      receptor-mediated neuroprotective effects. This study was performed to test the
      hypothesis that nitrobenzylthioinosine (NBMPR), a selective and potent inhibitor
      of one adenosine transporter subtype termed ENT1, or es, can protect against
      ischemic neuronal injury by enhancing adenosine levels and potentiating adenosine
      receptor-mediated effects, including attenuation of the cellular production and
      release of tumor necrosis factor-alpha (TNF-alpha). In rats, the phosphorylated
      prodrug form of NBMPR, NBMPR-phosphate, or saline was administered by
      intracerebroventricular injection 30 min before forebrain ischemia. Seven days
      following the ischemic episode, rats were killed, and neuronal damage in the CA1
      region of the hippocampus was assessed. The number of pyramidal neurons was
      significantly (p < 0.001) greater in the NBMPR-P treatment group. A trend toward
      protection was still evident at 28 days postreperfusion. Adenosine increased
      significantly during ischemia to levels eight- to 85-fold above basal. NBMPR-P
      treatment did not cause statistically significant increases in ischemic adenosine
      levels; however, this treatment tended to increase adenosine levels in all brain
      regions at 7 min postreperfusion. Ischemia-induced expression of TNF-alpha was
      not altered by NBMPR-P treatment, and the nonselective adenosine receptor
      antagonist 8-(p-sulfophenyl) theophylline did not abolish the neuroprotective
      effects of NBMPR-P treatment. These data indicate that NBMPR can protect CA1
      pyramidal neurons from ischemic death without statistically significant effects
      on adenosine levels or adenosine receptor-mediated inhibition of the
      proinflammatory cytokine TNF-alpha.

PMID- 10899958
TI  - Tissue distribution, autoradiography, and metabolism of 4-(2'-methoxyphenyl)-1
      [2' -[N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethyl]piperazine (p-[(18)F]MPPF),
      a new serotonin 5-HT(1A) antagonist for positron emission tomography: An In vivo
      study in rats.
AB  - The in vivo behavior of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p
      [(18)F]fluorobenzamido ]ethyl]-piperazine (p-[(18)F]MPPF), a new serotonin 5
      HT(1A) antagonist, was studied in awake, freely moving rats. Biodistribution
      studies showed that the carbon-fluorine bond was stable in vivo, that this
      compound was able to cross the blood-brain barrier, and that a general diffusion
      equilibrium could account for the availability of the tracer. The great quantity
      of highly polar metabolites found in plasma did not contribute to the small
      amounts of metabolites found in hippocampus, frontal cortex, and cerebellum.
      Exvivo p-[(18)F]MPPF and in vitro 8-hydroxy-2-(di-n-[(3)H]propylamino)tetralin
      autoradiography were compared both qualitatively and quantitatively. Qualitative
      evaluation proved that the same brain regions were labeled and that the p
      [(18)F]MPPF labeling is (a) in total agreement with the known distribution of 5
      HT(1A) receptors in rats and (b) characterized by very low nonspecific binding.
      Quantitative comparison demonstrated that the in vivo labeling pattern obtained
      with p-[(18)F]MPPF cannot be explained by differences in regional blood flow,
      capillary density, or permeability. The 5-HT(1A) specificity of p-[(18)F]MPPF and
      binding reversibility were confirmed in vivo with displacement experiments. Thus,
      this compound can be used to evaluate parameters characterizing 5-HT(1A) binding
      sites in the brain.

PMID- 10899959
TI  - Preconditioning with cortical spreading depression decreases intraischemic
      cerebral glutamate levels and down-regulates excitatory amino acid transporters
      EAAT1 and EAAT2 from rat cerebal cortex plasma membranes.
AB  - We previously reported a 50% reduction in cortical infarct volume following
      transient focal cerebral ischemia in rats preconditioned 3 days earlier with
      cortical spreading depression (CSD). The mechanism of the protective effect of
      prior CSD remains unknown. Recent studies demonstrate reversal of excitatory
      amino acid transporters (EAATs) to be a principal cause for elevated
      extracellular glutamate levels during cerebral ischemia. The present study
      measured the effect of CSD preconditioning on (a) intraischemic glutamate levels
      and (b) regulation of glutamate transporters within the ischemic cortex of the
      rat. Three days following either CSD or sham preconditioning, rats were subjected
      to 200 min of focal cerebral ischemia, and extracellular glutamate concentration
      was measured by in vivo microdialysis. Cortical glutamate exposure decreased 70%
      from 1,772.4 +/- 1,469.2 microM-min in sham-treated (n = 8) to 569.0 +/- 707.8
      microM-min in CSD-treated (n = 13) rats (p <0.05). The effect of CSD
      preconditioning on glutamate transporter levels in plasma membranes (PMs)
      prepared from rat cerebral cortex was assessed by western blot analysis. Down
      regulation of the glial glutamate transporter isoforms EAAT2 and EAAT1 from the
      PM fraction was observed at 1, 3, and 7 days but not at 0 or 21 days after CSD.
      Semiquantitative lane analysis showed a maximal decrease of 90% for EAAT2 and 50%
      for EAAT1 at 3 days post-CSD. The neuronal isoform EAAT3 was unaffected by CSD.
      This period of down-regulation coincides with the time frame reported for induced
      ischemic tolerance. These data are consistent with reversal of glutamate
      transporter function contributing to glutamate release during ischemia and
      suggest that down-regulation of these transporters may contribute to ischemic
      tolerance induced by CSD.

PMID- 10899960
TI  - Correlation between caspase-3 activation and three different markers of DNA
      damage in neonatal cerebral hypoxia-ischemia.
AB  - Caspase-3 has been identified as a key protease that, by targeting a limited
      number of proteins, can disrupt essential homeostatic processes and initiate an
      orderly disassembly of cells, including degradation of genomic DNA. We
      demonstrate the usefulness of an antibody specific for activated caspase-3 in a
      model of neonatal rat hypoxia-ischemia (Hl) and correlate the spatial and
      temporal activation of caspase-3 with three different markers of DNA damage and
      with the loss of a neuronal marker [microtubule-associated protein 2 (MAP 2)]. An
      oligonucleotide hairpin probe (HPP) with one base overhang in the 3' end
      displayed a close colocalization with caspase-3 activation at 3 h post-Hl,
      whereas terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      (TUNEL) appeared later (24 h post-Hl). A monoclonal antibody against single
      stranded DNA appeared to stain an entirely different population of cells, not
      positive for active caspase-3, HPP, or TUNEL at this time point. After 24 h of
      reperfusion, however, when cellular injury is extensive, all markers stained a
      large number of cells with a high degree of colocalization, and all markers
      delineated regions with loss of MAP 2. We conclude that the HPP shows the best
      correlation with pathological caspase-3 activation in this model.

PMID- 10899961
TI  - Early alterations in gene expression and cell morphology in a mouse model of
      Huntington's disease.
AB  - Several mouse models for Huntington's disease (HD) have been produced to date.
      Based on differences in strain, promoter, construct, and number of glutamines,
      these models have provided a broad spectrum of neurological symptoms, ranging
      from simple increases in aggressiveness with no signs of neuropathology, to
      tremors and seizures in absence of degeneration, to neurological symptoms in the
      presence of gliosis and TUNEL (terminal deoxynucleotidyl transferase-mediated
      dUTP nick end-labeling) positivity, and finally to selective striatal damage
      associated with electrophysiological and behavioral abnormalities. We decided to
      analyze the morphology of striatum and hippocampus from a mouse transgenic line
      obtained by microinjection of exon 1 from the HD gene after introduction of a
      very high number of CAG repeat units. We found a massive darkening and compacting
      of striatal and hippocampal neurons in affected mice, associated with a lower
      degree of more classical apoptotic cell condensation. We then explored whether
      this morphology could be explained with alterations in gene expression by
      hybridizing normal and affected total brain RNA to a panel of 588 known mouse
      cDNAs. We show that some genes are significantly and consistently up-regulated
      and that others are down-regulated in the affected brains. Here we discuss the
      possible significance of these alterations in neuronal morphology and gene
      expression.

PMID- 10899962
TI  - No evidence for increased oxidative damage to lipids, proteins, or DNA in
      Huntington's disease.
AB  - It has been proposed that mitochondrial dysfunction and excitotoxic mechanisms
      lead to oxidative damage in the brain of Huntington;s disease patients. We sought
      evidence that increased oxidative damage occurs by examining postmortem brain
      material from patients who had died with clinically and pathologically diagnosed
      Huntington's disease. Oxidative damage was measured using methods that have
      already demonstrated the presence of increased oxidative damage in Parkinson's
      disease, Alzheimer's disease, and senile dementia of the Lewy body type. No
      alterations in the levels of lipid peroxidation (as measured by lipid peroxides
      and thiobarbituric acid-malondialdehyde adducts) were found in the caudate
      nucleus, putamen, or frontal cortex of patients with Huntington's disease
      compared with normal controls. Similarly, there were no elevations in the levels
      of 8-hydroxyguanine or of a wide range of other markers of oxidative DNA damage.
      Levels of protein carbonyls in these tissues were also unaltered. Our data
      suggest that oxidative stress is not a major component of the degenerative
      processes occurring in Huntington's disease, or at least not to the extent that
      occurs in other neurodegenerative disorders.

PMID- 10899963
TI  - Malonate and 3-nitropropionic acid neurotoxicity are reduced in transgenic mice
      expressing a caspase-1 dominant-negative mutant.
AB  - Increasing evidence implicates caspase-1-mediated cell death as a major mechanism
      of neuronal death in neurodegenerative diseases. In the present study we
      investigated the role of caspase-1 in neurotoxic experimental animal models of
      Huntington's disease (HD) by examining whether transgenic mice expressing a
      caspase-1 dominant-negative mutant are resistant to malonate and 3-nitropropionic
      acid (3-NP) neurotoxicity. Intrastriatal injection of malonate resulted in
      significantly smaller striatal lesions in mutant caspase-1 mice than those
      observed in littermate control mice. Caspase-1 was significantly activated
      following malonate intrastriatal administration in control mice but significantly
      attenuated in mutant caspase-1 mice. Systemic 3-NP treatment induced selective
      striatal lesions that were significantly smaller within mutant caspase-1 mice
      than in littermate control mice. These results provide further evidence of a
      functional role for caspase-1 in both malonate- and 3-NP-mediated neurotoxin
      models of HD.

PMID- 10899964
TI  - Structure of a major oligosaccharide of PASII/PMP22 glycoprotein in bovine
      peripheral nerve myelin.
AB  - The amino acid sequence of the glycopeptide obtained from bovine PASII/PMP22
      protein in the PNS myelin was determined to be Gln-Asn-Cys-Ser-Thr, where the
      asparagine was glycosylated. To eliminate all the contaminated P(o) glycopeptides
      from the PASII/PMP22 glycopeptide preparation, we used a fluorescent probe, N-[2
      (2-pyridylamino)ethyl]maleimide, which reacts with the cysteine of the
      PASII/PMP22 glycopeptides. The labeled PASII/PMP22 glycopeptides were isolated by
      HPLC and were digested further with glycopeptidase A. The resultant
      oligosaccharides were conjugated with 2-aminopyridine (PA) as a fluorescent tag.
      One major PA-oligosaccharide, OPPE1, was purified by HPLC. The structure of OPPE1
      was elucidated by fast atom bombardment mass spectrometry and (1)H-NMR studies
      and comparing the derivatives of PA-OPPE1 and PA-oligosaccharides of gamma
      globulin on HPLC. The structure, SO(4)-3GlcAbeta1-3Galbeta1-4GlcNAcbeta1
      2Manalpha1+ ++-6(GlcNAcbeta1-4) (GlcNAcbeta1-2Manalpha1-3)Manbeta1-4GlcNAcbeta1-
      4(Fucalpha1-6)GlcNAc- PA, was identical to the pyridylaminated form of the major
      oligosaccharide D8 of bovine P(o) previously reported.

PMID- 10899965
TI  - Determination of the phospholipid precursor of anandamide and other N
      acylethanolamine phospholipids before and after sodium azide-induced toxicity in
      cultured neocortical neurons.
AB  - Phospholipase D-mediated hydrolysis of N-acylethanolamine phospholipids (NAPEs)
      releases anandamide and other N-acylethanolamines, resulting in different actions
      at cellular targets in the CNS. Recently, we have demonstrated that these N-acyl
      lipids accumulate in cultured neocortical neurons subjected to sodium azide
      induced cell injury. We here extend the information on the NAPE response,
      reporting on the composition of N-acylspecies of NAPE, employing a new
      methodological approach of HPLC-coupled electrospray ionization mass
      spectrometry. Exposure to sodium azide (5 mM) increased the total amount of NAPE
      threefold over control levels; however, no alteration of the relative composition
      of NAPE species was detected. The anandamide precursor (20 : 4-NAPE) constituted
      only 0.1% of all NAPEs detected in the neurons. Total NAPE species in control
      cells amounted to 956-1,060 pmol/10(7) cells. Moreover, we detected the presence
      of an unknown NAPE species with molecular weight identical to 20 : 4-NAPE. This
      may suggest the presence of a putative stereoisomer of the anandamide precursor
      with at least one trans-configured double bond in the N-arachidonoyl moiety.
      These results show that with the present method, neuronal NAPE species can be
      identified and quantified with respect to N-acyl composition, including a trans
      isomer of the anandamide precursor. The anandamide precursor is up-regulated to
      the same extent as other NAPEs upon neuronal injury.

PMID- 10899966
TI  - Regulation of eukaryotic initiation factor 4E phosphorylation in the nervous
      system of Aplysia californica.
AB  - We have used an antibody that specifically recognizes eukaryotic initiation
      factor 4E (eIF4E) when it is phosphorylated at Ser(207) to characterize eIF4E
      phosphorylation in the nervous system of APLYSIA: The level of phosphorylated
      eIF4E, but not the level of total eIF4E, was significantly correlated with the
      basal rate of translation measured from different animals. Serotonin (5-HT), a
      transmitter that regulates the rate of translation in APLYSIA: neurons, had mixed
      effects on eIF4E phosphorylation. 5-HT decreased eIF4E phosphorylation in sensory
      cell clusters through activation of protein kinase C. 5-HT increased eIF4E
      phosphorylation in the whole pleural ganglia. In the APLYSIA: nervous system,
      eIF4E phosphorylation correlated with phosphorylation of the p38 MAP kinase, but
      not the p42 MAP kinase (ERK). Furthermore, an inhibitor of the p38 MAP kinase
      significantly decreased basal eIF4E phosphorylation, but an inhibitor of the MAP
      or ERK kinase (MEK) did not. Despite the correlation of eIF4E phosphorylation
      with the basal rate of translation, inhibition of eIF4E phosphorylation by an
      inhibitor of the p38 MAP kinase did not significantly decrease the rate of
      translation.

PMID- 10899967
TI  - Real-time analysis of preprotachykinin promoter activity in single cortical
      neurons.
AB  - Technological limitations have hindered the study of gene elements regulating
      transcription within CNS neurons. In the present stuides, rat cortical brain
      slices endogenously expressing the preprotachykinin (PPT) gene were transfected
      with gene constructs encompassing green fluorescent protein (GFP) under the
      control of the PPT promoter. These slices were maintained in organotypic culture
      so that the fluorescence intensity within individual living cells could be
      quantified using laser scanning confocal microscopy before and after application
      of stimulatory agents. Combined treatment with forskolin and elevated potassium
      significantly increased expression of both endogenous PPT mRNA and the PPT
      promoter-GFP construct. The ability to follow fluorescence changes within single
      neurons in real time offers a powerful "within-subject" experimental approach for
      analysis of neural gene promoters.

PMID- 10899968
TI  - Striatal serotonin receptors and dopamine release.

PMID- 10899969
TI  - Mum's the word: MOM and modifiers of transcriptional gene silencing.

PMID- 10899970
TI  - Gene traps: tools for plant development and genomics.

PMID- 10899971
TI  - Comparative sequence analysis of plant nuclear genomes:m microcolinearity and its
      many exceptions.

PMID- 10899972
TI  - A unique 33-kD cysteine proteinase accumulates in response to larval feeding in
      maize genotypes resistant to fall armyworm and other Lepidoptera.
AB  - Plants respond to insect feeding with a number of defense mechanisms. Using maize
      genotypes derived from Antiquan germ plasm that are resistant to Lepidoptera, we
      have demonstrated that a unique 33-kD cysteine proteinase accumulates in the
      whorl in response to larval feeding. The abundance of the proteinase increased
      dramatically at the site of larval feeding after 1 hr of infestation and
      continued to accumulate for as long as 7 days. The 33-kD cysteine proteinase was
      most abundant in the yellow-green portion of the whorl-the normal site of larval
      feeding and the tissue that has the greatest inhibitory effect on larval growth
      in bioassays. The proteinase was expressed in response to wounding and was found
      in senescent leaves. It may be a marker of programmed cell death. The gene coding
      for the proteinase, mir1, has been transformed into Black Mexican Sweet callus.
      When larvae were reared on callus expressing the proteinase, their growth was
      inhibited approximately 60 to 80%. The expression of a cysteine proteinase,
      instead of a cysteine proteinase inhibitor, may be a novel insect defense
      mechanism in plants.

PMID- 10899973
TI  - The arabidopsis DELAYED DEHISCENCE1 gene encodes an enzyme in the jasmonic acid
      synthesis pathway.
AB  - delayed dehiscence1 is an Arabidopsis T-DNA mutant in which anthers release
      pollen grains too late for pollination to occur. The delayed dehiscence1 defect
      is caused by a delay in the stomium degeneration program. The gene disrupted in
      delayed dehiscence1 encodes 12-oxophytodienoate reductase, an enzyme in the
      jasmonic acid biosynthesis pathway. We rescued the mutant phenotype by exogenous
      application of jasmonic acid and obtained seed set from previously male-sterile
      plants. In situ hybridization studies showed that during the early stages of
      floral development, DELAYED DEHISCENCE1 mRNA accumulated within all floral
      organs. Later, DELAYED DEHISCENCE1 mRNA accumulated specifically within the
      pistil, petals, and stamen filaments. DELAYED DEHISCENCE1 mRNA was not detected
      in the stomium and septum cells of the anther that are involved in pollen
      release. The T-DNA insertion in delayed dehiscence1 eliminated both DELAYED
      DEHISCENCE1 mRNA accumulation and 12-oxophytodienoate reductase activity. These
      experiments suggest that jasmonic acid signaling plays a role in controlling the
      time of anther dehiscence within the flower.

PMID- 10899974
TI  - Light-induced nuclear translocation of endogenous pea phytochrome A visualized by
      immunocytochemical procedures.
AB  - Although the physiological functions of phytochrome A (PhyA) are now known, the
      distribution of endogenous PhyA has not been examined. We have visualized
      endogenous PhyA apoprotein (PHYA) by immunolabeling cryosections of pea tissue,
      using PHYA-deficient mutants as negative controls. By this method, we examined
      the distribution of PHYA in different tissues and changes in its intracellular
      distribution in response to light. In apical hook cells of etiolated seedlings,
      PHYA immunolabeling was distributed diffusely in the cytosol. Exposure to
      continuous far-red (cFR) light caused a redistribution of the immunolabeling to
      the nucleus, first detectable after 1.5 hr and greatest at 4.5 hr. During this
      time, the amounts of spectrally active phytochrome and PHYA did not decline
      substantially. Exposure to continuous red (cR) light or to a brief pulse of red
      light also resulted in redistribution of immunolabeling to the nucleus, but this
      occurred much more rapidly and with a different pattern of intranuclear
      distribution than it did in response to cFR light. Exposures to cR light resulted
      in loss of immunolabeling, which was associated with PHYA degradation. These
      results indicate that the light-induced intracellular location of PHYA is
      wavelength dependent and imply that this is important for PhyA activity.

PMID- 10899975
TI  - Cucumber mosaic virus D satellite RNA-induced programmed cell death in tomato.
AB  - D satellite RNA (satRNA) with its helper virus, namely, cucumber mosaic virus,
      causes systemic necrosis in tomato. The infected plant exhibits a distinct
      spatial and temporal cell death pattern. The distinct features of chromatin
      condensation and nuclear DNA fragmentation indicate that programmed cell death is
      involved. In addition, satRNA localization and terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labeling show that cell death
      is initiated from the infected phloem or cambium cells and spreads to other
      nearby infected cells. Timing of the onset of necrosis after inoculation
      implicates the involvement of cell developmental processes in initiating tomato
      cell death. Analysis of the accumulation of minus- and plus-strand satRNAs in the
      infected plants indicates a correlation between high amounts of minus-strand
      satRNA and tomato cell death.

PMID- 10899976
TI  - Extensive duplication and reshuffling in the Arabidopsis genome.
AB  - Systematic analysis of the Arabidopsis genome provides a basis for detailed
      studies of genome structure and evolution. Members of multigene families were
      mapped, and random sequence alignment was used to identify regions of extended
      similarity in the Arabidopsis genome. Detailed analysis showed that the number,
      order, and orientation of genes were conserved over large regions of the genome,
      revealing extensive duplication covering the majority of the known genomic
      sequence. Fine mapping analysis showed much rearrangement, resulting in a
      patchwork of duplicated regions that indicated deletion, insertion, tandem
      duplication, inversion, and reciprocal translocation. The implications of these
      observations for evolution of the Arabidopsis genome as well as their usefulness
      for analysis and annotation of the genomic sequence and in comparative genomics
      are discussed.

PMID- 10899977
TI  - Interactions between abscisic acid and ethylene signaling cascades.
AB  - We screened for mutations that either enhanced or suppressed the abscisic acid
      (ABA)-resistant seed germination phenotype of the Arabidopsis abi1-1 mutant.
      Alleles of the constitutive ethylene response mutant ctr1 and ethylene
      insensitive mutant ein2 were recovered as enhancer and suppressor mutations,
      respectively. Using these and other ethylene response mutants, we showed that the
      ethylene signaling cascade defined by the ETR1, CTR1, and EIN2 genes inhibits ABA
      signaling in seeds. Furthermore, epistasis analysis between ethylene- and ABA
      insensitive mutations indicated that endogenous ethylene promotes seed
      germination by decreasing sensitivity to endogenous ABA. In marked contrast to
      the situation in seeds, ein2 and etr1-1 roots were resistant to both ABA and
      ethylene. Our data indicate that ABA inhibition of root growth requires a
      functional ethylene signaling cascade, although this inhibition is apparently not
      mediated by an increase in ethylene biosynthesis. These results are discussed in
      the context of the other hormonal regulations controlling seed germination and
      root growth.

PMID- 10899978
TI  - Regulation of abscisic acid signaling by the ethylene response pathway in
      Arabidopsis.
AB  - Although abscisic acid (ABA) is involved in a variety of plant growth and
      developmental processes, few genes that actually regulate the transduction of the
      ABA signal into a cellular response have been identified. In an attempt to
      determine negative regulators of ABA signaling, we identified mutants, designated
      enhanced response to ABA3 (era3), that increased the sensitivity of the seed to
      ABA. Biochemical and molecular analyses demonstrated that era3 mutants
      overaccumulate ABA, suggesting that era3 is a negative regulator of ABA
      synthesis. Subsequent genetic analysis of era3 alleles, however, showed that
      these are new alleles at the ETHYLENE INSENSITIVE2 locus. Other mutants defective
      in their response to ethylene also showed altered ABA sensitivity; from these
      results, we conclude that ethylene appears to be a negative regulator of ABA
      action during germination. In contrast, the ethylene response pathway positively
      regulates some aspects of ABA action that involve root growth in the absence of
      ethylene. We discuss the response of plants to ethylene and ABA in the context of
      how these two hormones could influence the same growth responses.

PMID- 10899979
TI  - Ca(2)+-stimulated exocytosis in maize coleoptile cells.
AB  - Changes in membrane capacitance (C(m)) after photolysis of the caged Ca(2)+
      compound dimethoxynitrophenamine were studied in protoplasts from maize
      coleoptiles. Changes in C(m) values resulting from increased concentrations of
      free Ca(2)+ in the cytoplasm ([Ca(2)+](cyt)) were interpreted as representing
      changes in [Ca(2)+](cyt)-sensitive exocytosis and endocytosis. A continuous
      increase in [Ca(2)+](cyt) resulted in a sigmoidal increase in C(m) values with a
      half-maximal concentration at approximately 1 microM. The steep increase in C(m)
      values was followed by a variable slow phase in changing C(m) values. When
      [Ca(2)+](cyt) increased at a rate of 0.6 micromol L(-)(1) sec(-)(1), the initial
      steep increase in C(m) values lasted approximately 5 to 10 sec. During this time,
      protoplasts increased in surface area by approximately 2.5%. The biphasic
      dynamics of [Ca(2)+](cyt)-stimulated increases in C(m) values can be described by
      a kinetic model containing two pools of vesicles with two [Ca(2)+](cyt)-sensitive
      steps in the exocytotic pathway.

PMID- 10899980
TI  - KORRIGAN, an Arabidopsis endo-1,4-beta-glucanase, localizes to the cell plate by
      polarized targeting and is essential for cytokinesis.
AB  - The formation of the cell plate, a unique structure in dividing plant cells, is
      pivotal for cytokinesis. A mutation in the Arabidopsis KORRIGAN (KOR) gene causes
      the formation of aberrant cell plates, incomplete cell walls, and multinucleated
      cells, leading to severely abnormal seedling morphology. The mutant, designed
      kor1-2, was identified as a stronger allele than the previously identified kor1
      1, which appears to be defective only in cell elongation. KOR1 encodes an endo
      1,4-beta-d-glucanase with a transmembrane domain and two putative polarized
      targeting signals in the cytosolic tail. When expressed in tobacco BY2 cells, a
      KOR1-GFP (green fluorescence protein) fusion protein was localized to growing
      cell plates. Substitution mutations in the polarized targeting motifs of KOR1
      caused the fusion proteins to localize to the plasma membrane as well. Expression
      of these mutant genes in kor1-2 plants complemented only the cell elongation
      defect but not the cytokinesis defect, indicating that polarized targeting of
      KOR1 to forming cell plates is essential for cytokinesis. Our results suggest
      that KOR1 plays a critical role during cytokinesis.

PMID- 10899981
TI  - SUT2, a putative sucrose sensor in sieve elements.
AB  - In leaves, sucrose uptake kinetics involve high- and low-affinity components. A
      family of low- and high-affinity sucrose transporters (SUT) was identified. SUT1
      serves as a high-affinity transporter essential for phloem loading and long
      distance transport in solanaceous species. SUT4 is a low-affinity transporter
      with an expression pattern overlapping that of SUT1. Both SUT1 and SUT4 localize
      to enucleate sieve elements of tomato. New sucrose transporter-like proteins,
      named SUT2, from tomato and Arabidopsis contain extended cytoplasmic domains,
      thus structurally resembling the yeast sugar sensors SNF3 and RGT2. Features
      common to these sensors are low codon bias, environment of the start codon, low
      expression, and lack of detectable transport activity. In contrast to LeSUT1,
      which is induced during the sink-to-source transition of leaves, SUT2 is more
      highly expressed in sink than in source leaves and is inducible by sucrose.
      LeSUT2 protein colocalizes with the low- and high-affinity sucrose transporters
      in sieve elements of tomato petioles, indicating that multiple SUT mRNAs or
      proteins travel from companion cells to enucleate sieve elements. The SUT2 gene
      maps on chromosome V of potato and is linked to a major quantitative trait locus
      for tuber starch content and yield. Thus, the putative sugar sensor identified
      colocalizes with two other sucrose transporters, differs from them in kinetic
      properties, and potentially regulates the relative activity of low- and high
      affinity sucrose transport into sieve elements.

PMID- 10899982
TI  - Endogenous targets of transcriptional gene silencing in Arabidopsis.
AB  - Transcriptional gene silencing (TGS) frequently inactivates foreign genes
      integrated into plant genomes but very likely also suppresses an unknown subset
      of chromosomal information. Accordingly, RNA analysis of mutants impaired in
      silencing should uncover endogenous targets of this epigenetic regulation. We
      compared transcripts from wild-type Arabidopsis carrying a silent transgene with
      RNA from an isogenic transgene-expressing TGS mutant. Two cDNA clones were
      identified representing endogenous RNA expressed only in the mutant. The
      synthesis of these RNAs was found to be released in several mutants affected in
      TGS, implying that TGS in general and not a particular mutation controls the
      transcriptional activity of their templates. Detailed analysis revealed that the
      two clones are part of longer transcripts termed TSI (for transcriptionally
      silent information). Two major classes of related TSI transcripts were found in a
      mutant cDNA library. They are synthesized from repeats present in heterochromatic
      pericentromeric regions of Arabidopsis chromosomes. These repeats share sequence
      homology with the 3' terminal part of the putative retrotransposon Athila.
      However, the transcriptional activation does not include the transposon itself
      and does not promote its movement. There is no evidence for a general release of
      silencing from retroelements. Thus, foreign genes in plants encounter the
      epigenetic control normally directed, at least in part, toward a subset of
      pericentromeric repeats.

PMID- 10899983
TI  - The C-terminal dilysine motif confers endoplasmic reticulum localization to type
      I membrane proteins in plants.
AB  - The tomato Cf-9 disease resistance gene encodes a type I membrane protein
      carrying a cytosolic dilysine motif. In mammals and yeast, this motif promotes
      the retrieval of type I membrane proteins from the Golgi apparatus to the
      endoplasmic reticulum (ER). To test whether the C-terminal KKXX signal of Cf-9 is
      functional as a retrieval motif and to investigate its role in plants, green
      fluorescent protein (GFP) was fused to the transmembrane domain of Cf-9 and
      expressed in yeast, Arabidopsis, and tobacco cells. The fusion protein was
      targeted to the ER in each of these expression systems, and mutation of the KKXX
      motif to NNXX led to secretion of the fusion protein. In yeast, the mutant
      protein reached the vacuole, but plants secreted it as a soluble protein after
      proteolytic removal of the transmembrane domain. Triple hemagglutinin (HA)-tagged
      full-length Cf-9 was also targeted to the ER in tobacco cells, and cleavage was
      also observed for the NNXX mutant protein, suggesting an endoprotease recognition
      site located within the Cf-9 lumenal sequence common to both the GFP- and the HA
      tagged fusions. Our results indicate that the KKXX motif confers ER localization
      in plants as well as mammals and yeast and that Cf-9 is a resident protein of the
      ER.

PMID- 10899984
TI  - Sustained but not transient phytochrome A signaling targets a region of an
      Lhcb1*2 promoter not necessary for phytochrome B action.
AB  - Current evidence is inconclusive regarding the point of signaling convergence
      downstream from different members of the phytochrome family. In transgenic
      Arabidopsis, the activity of a reporter enzyme under the control of the -453 to
      +67 fragment of an Lhcb1*2 promoter shows very low fluence responses (VLFRs) and
      high-irradiance responses (HIRs) mediated by phytochrome A and low-fluence
      responses (LFRs) mediated by phytochrome B. A 5' deletion of the promoter to -134
      abolished the HIR without affecting VLFR or LFR. In transgenic tobacco, VLFR and
      LFR were observed for the -176 to -31 or -134 to -31 fragments of Lhcb1*2 fused
      to 35S cauliflower mosaic virus minimal promoters, but only the largest fragment
      showed HIR. We propose that sustained activation of phytochrome A with far-red
      light initiates a signaling cascade that deviates from phytochrome B signaling
      and transient phytochrome A signaling and that this divergence extends as far as
      the Lhcb1*2 promoter.

PMID- 10899985
TI  - Heat shock protein HSP101 binds to the Fed-1 internal light regulator y element
      and mediates its high translational activity.
AB  - The internal light-regulatory element (iLRE) of ferredoxin (Fed-1) mRNA,
      comprising the 5' leader and at least the first 13 codons of the open reading
      frame, controls transcript abundance after illumination of the plant in a
      translation-dependent manner. We have characterized the RNA binding activities
      associated with the Fed-1 iLRE and have identified one activity as the heat shock
      protein HSP101, a protein shown to bind the 5' leader of tobacco mosaic virus.
      HSP101 was sufficient and necessary to mediate a high level of translational
      activity from a Fed-1 iLRE-containing mRNA in yeast. Moreover, the Fed-1 iLRE
      substantially enhanced translation of reporter mRNAs in plant protoplasts
      expressing HSP101. Expression of HSP101 was subject to developmental regulation
      in leaves in that expression was highest in young leaves. These data suggest that
      Fed-1 mRNA may use the HSP101 regulatory mechanism as a means of ensuring a high
      level of translation required for the light-mediated regulation of Fed-1 mRNA
      stability.

PMID- 10899986
TI  - In vivo colocalization of xyloglucan endotransglycosylase activity and its donor
      substrate in the elongation zone of Arabidopsis roots.
AB  - We have developed a method for the colocalization of xyloglucan
      endotransglycosylase (XET) activity and the donor substrates to which it has
      access in situ and in vivo. Sulforhodamine conjugates of xyloglucan
      oligosaccharides (XGO-SRs), infiltrated into the tissue, act as acceptor
      substrate for the enzyme; endogenous xyloglucan acts as donor substrate.
      Incorporation of the XGO-SRs into polymeric products in the cell wall yields an
      orange fluorescence indicative of the simultaneous colocalization, in the same
      compartment, of active XET and donor xyloglucan chains. The method is specific
      for XET, as shown by competition experiments with nonfluorescent acceptor
      oligosaccharides, by negligible reaction with cello-oligosaccharide-SR conjugates
      that are not XET acceptor substrates, by heat lability, and by pH optimum. Thin
      layer chromatographic analysis of remaining unincorporated XGO-SRs showed that
      these substrates are not extensively hydrolyzed during the assays. A
      characteristic distribution pattern was found in Arabidopsis and tobacco roots:
      in both species, fluorescence was most prominent in the cell elongation zone of
      the root. Proposed roles of XET that include cell wall loosening and integration
      of newly synthesized xyloglucans could thus be supported.

PMID- 10899987
TI  - Alterations in the actin cytoskeleton of pollen tubes are induced by the self
      incompatibility reaction in Papaver rhoeas.
AB  - Self-incompatibility (SI) is a genetically controlled process used to prevent
      self-pollination. In Papaver rhoeas, the induction of SI is triggered by a Ca(2)+
      dependent signaling pathway that results in the rapid and S allele-specific
      inhibition of pollen tube tip growth. Tip growth of cells is dependent on a
      functioning actin cytoskeleton. We have investigated the effect of self
      incompatibility (S) proteins on the actin cytoskeleton in poppy pollen tubes.
      Here, we report that the actin cytoskeleton of incompatible pollen tubes is
      rapidly and dramatically rearranged during the SI response, not only in our in
      vitro SI system but also in vivo. We demonstrate that nonspecific inhibition of
      growth does not result in similar actin rearrangements. Because the SI-induced
      alterations are not observed if growth stops, this clearly demonstrates that
      these alterations are triggered by the SI signaling cascade rather than merely
      resulting from the consequent inhibition of growth. We establish a detailed time
      course of events and discuss the mechanisms that might be involved. Our data
      strongly implicate a role for the actin cytoskeleton as a target for signaling
      pathways involved in the SI response of P. rhoeas.

PMID- 10899988
TI  - HIV therapy: managing resistance.

PMID- 10899989
TI  - Neural circuits in the 21st century: synaptic networks of neurons and glia.

PMID- 10899990
TI  - Bt corn pollen impacts on nontarget lepidoptera: assessment of effects in nature.

PMID- 10899991
TI  - Generalized flows, intrinsic stochasticity, and turbulent transport.
AB  - The study of passive scalar transport in a turbulent velocity field leads
      naturally to the notion of generalized flows, which are families of probability
      distributions on the space of solutions to the associated ordinary differential
      equations which no longer satisfy the uniqueness theorem for ordinary
      differential equations. Two most natural regularizations of this problem, namely
      the regularization via adding small molecular diffusion and the regularization
      via smoothing out the velocity field, are considered. White-in-time random
      velocity fields are used as an example to examine the variety of phenomena that
      take place when the velocity field is not spatially regular. Three different
      regimes, characterized by their degrees of compressibility, are isolated in the
      parameter space. In the regime of intermediate compressibility, the two different
      regularizations give rise to two different scaling behaviors for the structure
      functions of the passive scalar. Physically, this means that the scaling depends
      on Prandtl number. In the other two regimes, the two different regularizations
      give rise to the same generalized flows even though the sense of convergence can
      be very different. The "one force, one solution" principle is established for the
      scalar field in the weakly compressible regime, and for the difference of the
      scalar in the strongly compressible regime, which is the regime of inverse
      cascade. Existence and uniqueness of an invariant measure are also proved in
      these regimes when the transport equation is suitably forced. Finally incomplete
      self similarity in the sense of Barenblatt and Chorin is established.

PMID- 10899992
TI  - Fluorescence microscopy with diffraction resolution barrier broken by stimulated
      emission.
AB  - The diffraction barrier responsible for a finite focal spot size and limited
      resolution in far-field fluorescence microscopy has been fundamentally broken.
      This is accomplished by quenching excited organic molecules at the rim of the
      focal spot through stimulated emission. Along the optic axis, the spot size was
      reduced by up to 6 times beyond the diffraction barrier. The simultaneous 2-fold
      improvement in the radial direction rendered a nearly spherical fluorescence spot
      with a diameter of 90-110 nm. The spot volume of down to 0.67 attoliters is 18
      times smaller than that of confocal microscopy, thus making our results also
      relevant to three-dimensional photochemistry and single molecule spectroscopy.
      Images of live cells reveal greater details.

PMID- 10899993
TI  - Compact stellarators with modular coils.
AB  - Compact stellarator designs with modular coils and only two or three field
      periods are now available; these designs have both good stability and quasiaxial
      symmetry providing adequate transport for a magnetic fusion reactor. If the
      bootstrap current assumes theoretically predicted values a three field period
      configuration is optimal, but if that net current turns out to be lower, a device
      with two periods and just 12 modular coils might be better. There are also
      attractive designs with quasihelical symmetry and four or five periods whose
      properties depend less on the bootstrap current. Good performance requires that
      there be a satisfactory magnetic well in the vacuum field, which is a property
      lacking in a stellarator-tokamak hybrid that has been proposed for a proof of
      principle experiment. In this paper, we present an analysis of stability for
      these configurations that is based on a mountain pass theorem asserting that, if
      two solutions of the problem of magnetohydrodynamic equilibrium can be found,
      then there has to be an unstable solution. We compare results of our theory of
      equilibrium, stability, and transport with recently announced measurements from
      the large LHD experiment in Japan.

PMID- 10899994
TI  - Polynesian origins: insights from the Y chromosome.
AB  - The question surrounding the colonization of Polynesia has remained
      controversial. Two hypotheses, one postulating Taiwan as the putative homeland
      and the other asserting a Melanesian origin of the Polynesian people, have
      received considerable attention. In this work, we present haplotype data based on
      the distribution of 19 biallelic polymorphisms on the Y chromosome in a sample of
      551 male individuals from 36 populations living in Southeast Asia, Taiwan,
      Micronesia, Melanesia, and Polynesia. Surprisingly, nearly none of the Taiwanese
      Y haplotypes were found in Micronesia and Polynesia. Likewise, a Melanesian
      specific haplotype was not found among the Polynesians. However, all of the
      Polynesian, Micronesian, and Taiwanese haplotypes are present in the extant
      Southeast Asian populations. Evidently, the Y-chromosome data do not lend support
      to either of the prevailing hypotheses. Rather, we postulate that Southeast Asia
      provided a genetic source for two independent migrations, one toward Taiwan and
      the other toward Polynesia through island Southeast Asia.

PMID- 10899996
TI  - m5C RNA and m5C DNA methyl transferases use different cysteine residues as
      catalysts.
AB  - A family of RNA m(5)C methyl transferases (MTases) containing over 55 members in
      eight subfamilies has been identified recently by an iterative search of the
      genomic sequence databases by using the known 16S rRNA m(5)C 967 MTase, Fmu, as
      an initial probe. The RNA m(5)C MTase family contained sequence motifs that were
      highly homologous to motifs in the DNA m(5)C MTases, including the ProCys
      sequence that contains the essential Cys catalyst of the functionally similar DNA
      modifying enzymes; it was reasonable to assign the Cys nucleophile to be that in
      the conserved ProCys. The family also contained an additional conserved Cys
      residue that aligns with the nucleophilic catalyst in m(5)U54 tRNA MTase.
      Surprisingly, the mutant of the putative Cys catalyst in the ProCys sequence was
      active and formed a covalent complex with 5-fluorocytosine-containing RNA,
      whereas the mutant at the other conserved Cys was inactive and unable to form the
      complex. Thus, notwithstanding the highly homologous sequences and similar
      functions, the RNA m(5)C MTase uses a different Cys as a catalytic nucleophile
      than the DNA m(5)C MTases. The catalytic Cys seems to be determined, not by the
      target base that is modified, but by whether the substrate is DNA or RNA. The
      function of the conserved ProCys sequence in the RNA m(5)C MTases remains
      unknown.

PMID- 10899995
TI  - A deoxyribonucleotidase in mitochondria: involvement in regulation of dNTP pools
      and possible link to genetic disease.
AB  - Three cytosolic and one plasma membrane-bound 5'-nucleotidases have been cloned
      and characterized. Their various substrate specificities suggest widely different
      functions in nucleotide metabolism. We now describe a 5'-nucleotidase in
      mitochondria. The enzyme, named dNT-2, dephosphorylates specifically the 5'- and
      2'(3')-phosphates of uracil and thymine deoxyribonucleotides. The cDNA of human
      dNT-2 codes for a 25.9-kDa polypeptide with a typical mitochondrial leader
      peptide, providing the structural basis for two-step processing during import
      into the mitochondrial matrix. The deduced amino acid sequence is 52% identical
      to that of a recently described cytosolic deoxyribonucleotidase (dNT-1). The two
      enzymes share many catalytic properties, but dNT-2 shows a narrower substrate
      specificity. Mitochondrial localization of dNT-2 was demonstrated by the
      mitochondrial fluorescence of 293 cells expressing a dNT-2-green fluorescent
      protein (GFP) fusion protein. 293 cells expressing fusion proteins without leader
      peptide or with dNT-1 showed a cytosolic fluorescence. During in vitro import
      into mitochondria, the preprotein lost the leader peptide. We suggest that dNT-2
      protects mitochondrial DNA replication from overproduction of dTTP, in particular
      in resting cells. Mitochondrial toxicity of dTTP can be inferred from a severe
      inborn error of metabolism in which the loss of thymidine phosphorylase led to
      dTTP accumulation and aberrant mitochondrial DNA replication. We localized the
      gene for dNT-2 on chromosome 17p11.2 in the Smith-Magenis syndrome-critical
      region, raising the possibility that dNT-2 is involved in the etiology of this
      genetic disease.

PMID- 10899997
TI  - Identification and characterization of an enzyme involved in the elongation of n
      6 and n-3 polyunsaturated fatty acids.
AB  - The enzymes that are involved in the elongation of fatty acids differ in terms of
      the substrates on which they act. To date, the enzymes specifically involved in
      the biosynthesis of polyunsaturated fatty acids have not yet been identified. In
      an attempt to identify a gene(s) encoding an enzyme(s) specific for the
      elongation of gamma-linolenic acid (GLA) (18:3n-6), a cDNA expression library was
      made from the fungus Mortierella alpina. The cDNA library constructed in a yeast
      expression vector was screened by measuring the expressed elongase activity
      [conversion of GLA to dihomo-GLA (20:3n-6)] from an individual yeast clone. In
      this report, we demonstrate the isolation of a cDNA (GLELO) whose encoded protein
      (GLELOp) was involved in the conversion of GLA to dihomo-GLA in an efficient
      manner (60% conversion). This cDNA contains a 957-nucleotide ORF that encodes a
      protein of 318 amino acids. Substrate specificity analysis revealed that this
      fungal enzyme acted also on stearidonic acid (18:4n-3). This report identifies
      and characterizes an elongase subunit that acts specifically on the two Delta6
      desaturation products, 18:3n-6 and 18:4n-3. When this GLELO cDNA was coexpressed
      with M. alpina Delta5-desaturase cDNA in yeast, it resulted in the conversion of
      GLA to arachidonic acid (20:4n-6) as well as the conversion of stearidonic acid
      to eicosopentaenoic acid (20:5n-3). Thus, this GLELO gene may play an critical
      role in the bio-production of both n-6 and n-3 polyunsaturated fatty acids.

PMID- 10899998
TI  - Modeling the dynamics of human hair cycles by a follicular automaton.
AB  - The hair follicle cycle successively goes through the anagen, catagen, telogen,
      and latency phases, which correspond, respectively, to hair growth, arrest,
      shedding, and absence before a new anagen phase is initiated. Experimental
      observations collected over a period of 14 years in a group of 10 male
      volunteers, alopecic and nonalopecic, allowed us to determine the characteristics
      of scalp hair follicle cycles. On the basis of these observations, we propose a
      follicular automaton model to simulate the dynamics of human hair cycles. The
      automaton model is defined by a set of rules that govern the stochastic
      transitions of each follicle between the successive states anagen, telogen, and
      latency, and the subsequent return to anagen. The transitions occur independently
      for each follicle, after time intervals given stochastically by a distribution
      characterized by a mean and a variance. The follicular automaton model accounts
      both for the dynamical transitions observed in a single follicle and for the
      behavior of an ensemble of independently cycling follicles. Thus, the model
      successfully reproduces the evolution of the fractions of follicle populations in
      each of the three phases, which fluctuate around steady-state or slowly drifting
      values. We apply the follicular automaton model to the study of spatial patterns
      of follicular growth that result from a spatially heterogeneous distribution of
      parameters such as the mean duration of anagen phase. When considering that
      follicles die or miniaturize after going through a critical number of successive
      cycles, the model can reproduce the evolution to hair patterns similar to well
      known types of diffuse or androgenetic alopecia.

PMID- 10899999
TI  - NMR structure of the bovine prion protein.
AB  - The NMR structures of the recombinant 217-residue polypeptide chain of the mature
      bovine prion protein, bPrP(23-230), and a C-terminal fragment, bPrP(121-230),
      include a globular domain extending from residue 125 to residue 227, a short
      flexible chain end of residues 228-230, and an N-terminal flexibly disordered
      "tail" comprising 108 residues for the intact protein and 4 residues for bPrP(121
      230), respectively. The globular domain contains three alpha-helices comprising
      the residues 144-154, 173-194, and 200-226, and a short antiparallel beta-sheet
      comprising the residues 128-131 and 161-164. The best-defined parts of the
      globular domain are the central portions of the helices 2 and 3, which are linked
      by the only disulfide bond in bPrP. Significantly increased disorder and mobility
      is observed for helix 1, the loop 166-172 leading from the beta-strand 2 to helix
      2, the end of helix 2 and the following loop, and the last turn of helix 3.
      Although there are characteristic local differences relative to the conformations
      of the murine and Syrian hamster prion proteins, the bPrP structure is
      essentially identical to that of the human prion protein. On the other hand,
      there are differences between bovine and human PrP in the surface distribution of
      electrostatic charges, which then appears to be the principal structural feature
      of the "healthy" PrP form that might affect the stringency of the species barrier
      for transmission of prion diseases between humans and cattle.

PMID- 10900000
TI  - NMR structures of three single-residue variants of the human prion protein.
AB  - The NMR structures of three single-amino acid variants of the C-terminal domain
      of the human prion protein, hPrP(121-230), are presented. In hPrP(M166V) and
      hPrP(R220K) the substitution is with the corresponding residue in murine PrP, and
      in hPrP(S170N) it is with the corresponding Syrian hamster residue. All three
      substitutions are in the surface region of the structure of the cellular form of
      PrP (PrP(C)) that is formed by the C-terminal part of helix 3, with residues 218
      230, and a loop of residues 166-172. This molecular region shows high species
      variability and has been implicated in specific interactions with a so far not
      further characterized "protein X," and it is related to the species barrier for
      transmission of prion diseases. As expected, the three variant hPrP(121-230)
      structures have the same global architecture as the previously determined wild
      type bovine, human, murine, and Syrian hamster prion proteins, but with the
      present study two localized "conformational markers" could be related with single
      amino acid exchanges. These are the length and quality of definition of helix 3,
      and the NMR-observability of the residues in the loop 166-172. Poor definition of
      the C-terminal part of helix 3 is characteristic for murine PrP and has now been
      observed also for hPrP(R220K), and NMR observation of the complete loop 166-172
      has so far been unique for Syrian hamster PrP and is now also documented for
      hPrP(S170N).

PMID- 10900001
TI  - Spermatogonial stem cell enrichment by multiparameter selection of mouse testis
      cells.
AB  - The spermatogonial stem cell initiates and maintains spermatogenesis in the
      testis. To perform this role, the stem cell must self replicate as well as
      produce daughter cells that can expand and differentiate to form spermatozoa.
      Despite the central importance of the spermatogonial stem cell to male
      reproduction, little is known about its morphological or biochemical
      characteristics. This results, in part, from the fact that spermatogonial stem
      cells are an extremely rare cell population in the testis, and techniques for
      their enrichment are just beginning to be established. In this investigation, we
      used a multiparameter selection strategy, combining the in vivo cryptorchid
      testis model with in vitro fluorescence-activated cell sorting analysis.
      Cryptorchid testis cells were fractionated by fluorescence-activated cell sorting
      analysis based on light-scattering properties and expression of the cell surface
      molecules alpha6-integrin, alphav-integrin, and the c-kit receptor. Two important
      observations emerged from these analyses. First, spermatogonial stem cells from
      the adult cryptorchid testis express little or no c-kit. Second, the most
      effective enrichment strategy, in this study, selected cells with low side
      scatter light-scattering properties, positive staining for alpha6-integrin, and
      negative or low alphav-integrin expression, and resulted in a 166-fold enrichment
      of spermatogonial stem cells. Identification of these characteristics will allow
      further purification of these valuable cells and facilitate the investigation of
      molecular mechanisms governing spermatogonial stem cell self renewal and
      hierarchical differentiation.

PMID- 10900002
TI  - Localization of alpha 1,3-fucosyltransferase VI in Weibel-Palade bodies of human
      endothelial cells.
AB  - Surface glycosylation of endothelial cells is relevant to various processes
      including coagulation, inflammation, metastasis, and lymphocyte homing. One of
      the essential sugars involved in these processes is fucose linked alpha1-->3 to N
      acetylglucosamine. A family of alpha1,3-fucosyltransferases (FucTs) called FucT
      III, IV, V, VI, VII, and IX is able to catalyze such fucosylations. Reverse
      transcription-PCR analysis revealed that human umbilical vein endothelial cells
      express all of the FucTs except FucT-IX. The predominant activity, as inferred by
      acceptor specificity of enzyme activity in cell lysates, is compatible with the
      presence of FucT-VI. By using an antibody to recombinant soluble FucT-VI, the
      enzyme colocalized with beta4-galactosyltransferase-1 to the Golgi apparatus. By
      using a polyclonal antiserum raised against a 17-aa peptide of the variable
      (stem) region of the FucT-VI, immunocytochemical staining of FucT-VI was
      restricted to Weibel-Palade bodies, as determined by colocalization with P
      selectin and von Willebrand factor. SDS/PAGE immunoblotting and amino acid
      sequencing of internal peptides confirmed the identity of the antigen isolated by
      the peptide-specific antibody as FucT-VI. Storage of a fucosyltransferase in
      Weibel-Palade bodies suggests a function independent of Golgi-associated
      glycosylation.

PMID- 10900003
TI  - Interpreting the universal phylogenetic tree.
AB  - The universal phylogenetic tree not only spans all extant life, but its root and
      earliest branchings represent stages in the evolutionary process before modern
      cell types had come into being. The evolution of the cell is an interplay between
      vertically derived and horizontally acquired variation. Primitive cellular
      entities were necessarily simpler and more modular in design than are modern
      cells. Consequently, horizontal gene transfer early on was pervasive, dominating
      the evolutionary dynamic. The root of the universal phylogenetic tree represents
      the first stage in cellular evolution when the evolving cell became sufficiently
      integrated and stable to the erosive effects of horizontal gene transfer that
      true organismal lineages could exist.

PMID- 10900004
TI  - Distinct spectra of somatic mutations accumulated with age in mouse heart and
      small intestine.
AB  - Somatic mutation accumulation has been implicated as a major cause of cancer and
      aging. By using a transgenic mouse model with a chromosomally integrated lacZ
      reporter gene, mutational spectra were characterized at young and old age in two
      organs greatly differing in proliferative activity, i.e., the heart and small
      intestine. At young age the spectra were nearly identical, mainly consisting of
      G. C to A.T transitions and 1-bp deletions. At old age, however, distinct
      patterns of mutations had developed. In small intestine, only point mutations
      were found to accumulate, including G.C to T.A, G.C to C.G, and A.T to C.G
      transversions and G.C to A.T transitions. In contrast, in heart about half of the
      accumulated mutations appeared to be large genome rearrangements, involving up to
      34 centimorgans of chromosomal DNA. Virtually all other mutations accumulating in
      the heart appeared to be G.C to A.T transitions at CpG sites. These results
      suggest that distinct mechanisms lead to organ-specific genome deterioration and
      dysfunction at old age.

PMID- 10900005
TI  - Internalization of CD26 by mannose 6-phosphate/insulin-like growth factor II
      receptor contributes to T cell activation.
AB  - CD26 is a T cell activation antigen known to bind adenosine deaminase and have
      dipeptidyl peptidase IV activity. Cross-linking of CD26 and CD3 with immobilized
      mAbs can deliver a costimulatory signal that contributes to T cell activation.
      Our earlier studies revealed that cross-linking of CD26 induces its
      internalization, the phosphorylation of a number of proteins involved in the
      signaling pathway, and subsequent T cell proliferation. Although these findings
      suggest the importance of internalization in the function of CD26, CD26 has only
      6 aa residues in its cytoplasmic region with no known motif for endocytosis. In
      the present study, we have identified the mannose 6-phosphate/insulin-like growth
      factor II receptor (M6P/IGFIIR) as a binding protein for CD26 and that mannose 6
      phosphate (M6P) residues in the carbohydrate moiety of CD26 are critical for this
      binding. Activation of peripheral blood T cells results in the mannose 6
      phosphorylation of CD26. In addition, the cross-linking of CD26 with an anti-CD26
      antibody induces not only capping and internalization of CD26 but also
      colocalization of CD26 with M6P/IGFIIR. Finally, both internalization of CD26 and
      the T cell proliferative response induced by CD26-mediated costimulation were
      inhibited by the addition of M6P, but not by glucose 6-phosphate or mannose 1
      phosphate. These results indicate that internalization of CD26 after cross
      linking is mediated in part by M6P/IGFIIR and that the interaction between
      mannose 6-phosphorylated CD26 and M6P/IGFIIR may play an important role in CD26
      mediated T cell costimulatory signaling.

PMID- 10900006
TI  - The serine and threonine residues in the Ig-alpha cytoplasmic tail negatively
      regulate immunoreceptor tyrosine-based activation motif-mediated signal
      transduction.
AB  - The B cell antigen receptor (BCR) is a multiprotein complex consisting of the
      membrane-bound Ig molecule and the Ig-alpha/Ig-beta heterodimer. On BCR
      engagement, Ig-alpha and Ig-beta become phosphorylated not only on tyrosine
      residues of the immunoreceptor tyrosine-based activation motif but also on serine
      and threonine residues. We have mutated all serine and threonine residues in the
      Ig-alpha tail to alanine and valine, respectively. The mutated Ig-alpha sequence
      was expressed either as a single-chain Fv/Ig-alpha molecule or in the context of
      the complete BCR. In both cases, the mutated Ig-alpha showed a stronger tyrosine
      phosphorylation than the wild-type Ig-alpha and initiated increased signaling on
      stimulation. These findings suggest that serine/threonine kinases can negatively
      regulate signal transduction from the BCR.

PMID- 10900008
TI  - Comparative T cell receptor repertoire selection by antigen after adoptive
      transfer: a glimpse at an antigen-specific preimmune repertoire.
AB  - The low frequency of precursor cells specific for any particular antigen (Ag)
      makes it difficult to characterize preimmune T cell receptor (TCR) repertoires
      and to understand repertoire selection during an immune response. We have
      undertaken a combined adoptive transfer single-cell PCR approach to probe the Ag
      specific preimmune repertoires of individual mice. Our strategy was to inject
      paired irradiated recipient mice with normal spleen cells prepared from
      individual donors and to compare the TCR repertoires subsequently selected during
      a CD8 response to a defined model Ag. We found that although some TCRs were
      shared, the TCR repertoires selected by mice receiving splenocytes from the same
      donor were not identical in terms of the TCRs selected and their relative
      frequencies. Our results together with computer simulations imply that individual
      mice express distinct Ag-specific preimmune TCR repertoires composed of expanded
      clones and that selection by Ag is a random process.

PMID- 10900009
TI  - The paradox of alloreactivity and self MHC restriction: quantitative analysis and
      statistics.
AB  - Although 1-24% of T cells are alloreactive, i.e., respond to MHC molecules
      encoded by a foreign haplotype, it is generally believed that T cells cannot
      recognize foreign peptides binding foreign MHC molecules. We show using a
      quantitative model that, if T cell selection and activation are affinity-driven,
      then an alloreactivity of 1-24% is incompatible with the textbook notion that
      self MHC restriction is absolute. If an average of 1% of clones are alloreactive,
      then according to our model, at most 20-fold more clones should, on average, be
      activated by antigens presented on self MHC than by antigens presented on foreign
      MHC. This ratio is at best 5 if alloreactivity is 5%. These results describe
      average properties of the murine immune system, but not the outcome of individual
      experiments. Using supercomputer technology, we simulated 100,000 MHC restriction
      experiments. Although the average restriction ratio was 7.1, restriction was
      absolute in 10% of the simulated experiments, greater than 100, although not
      absolute, in 29%, and below 6 in 24%. This extreme variability agrees with
      experimental estimates. Our analysis suggests that alloreactivity and average
      self MHC restriction both cannot be high, but that a low average restriction
      level is compatible with high levels in a significant number of experiments.

PMID- 10900007
TI  - alpha -galactosylceramide-activated Valpha 14 natural killer T cells mediate
      protection against murine malaria.
AB  - Natural killer T (NKT) cells are a unique population of lymphocytes that
      coexpress a semiinvariant T cell and natural killer cell receptors, which are
      particularly abundant in the liver. To investigate the possible effect of these
      cells on the development of the liver stages of malaria parasites, a glycolipid,
      alpha-galactosylceramide (alpha-GalCer), known to selectively activate Valpha14
      NKT cells in the context of CD1d molecules, was administered to sporozoite
      inoculated mice. The administration of alpha-GalCer resulted in rapid, strong
      antimalaria activity, inhibiting the development of the intrahepatocytic stages
      of the rodent malaria parasites Plasmodium yoelii and Plasmodium berghei. The
      antimalaria activity mediated by alpha-GalCer is stage-specific, since the course
      of blood-stage-induced infection was not inhibited by administration of this
      glycolipid. Furthermore, it was determined that IFN-gamma is essential for the
      antimalaria activity mediated by the glycolipid. Taken together, our results
      provide the clear evidence that NKT cells can mediate protection against an
      intracellular microbial infection.

PMID- 10900010
TI  - Activation of p53 in cervical carcinoma cells by small molecules.
AB  - In over 90% of cervical cancers and cancer-derived cell lines, the p53 tumor
      suppressor pathway is disrupted by human papillomavirus (HPV). The HPV E6 protein
      promotes the degradation of p53 and thus inhibits the stabilization and
      activation of p53 that would normally occur in response to HPV E7 oncogene
      expression. Restoration of p53 function in these cells by blocking this pathway
      should promote a selective therapeutic affect. Here we show that treatment with
      the small molecule nuclear export inhibitor, leptomycin B, and actinomycin D
      leads to the accumulation of transcriptionally active p53 in the nucleus of HeLa,
      CaSki, and SiHa cells. Northern blot analyses showed that both actinomycin D and
      leptomycin B reduced the amount of HPV E6-E7 mRNA whereas combined treatment with
      the drugs showed almost complete disappearance of the viral mRNA. The combined
      treatment activated p53-dependant transcription, and increases in both
      p21(WAF1/CIP1) and Hdm2 mRNA were seen. The combined treatment resulted in
      apoptotic death in the cells, as evidenced by nuclear fragmentation and PARP
      cleavage indicative of caspase 3 activity. These effects were greatly reduced by
      expressing a dominant negative p53 protein. The present study shows that small
      molecules can reactivate p53 in cervical carcinoma cells, and this reactivation
      is associated with an extensive biological response, including the induction of
      the apoptotic death of the cells.

PMID- 10900011
TI  - Elongin BC complex prevents degradation of von Hippel-Lindau tumor suppressor
      gene products.
AB  - Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene causes the
      familial cancer syndrome, VHL disease, characterized by a predisposition to renal
      cell carcinoma and other tumor types. Loss of VHL gene function also is found in
      a majority of sporadic renal carcinomas. A preponderance of the tumor-disposing
      inherited missense mutations detected in VHL disease are within the elongin
      binding domain of VHL. This region mediates the formation of a multiprotein VHL
      complex containing elongin B, elongin C, cul-2, and Rbx1. This VHL complex is
      thought to function as an E3 ubiquitin ligase. Here, we report that VHL proteins
      harboring mutations which disrupt elongin binding are unstable and rapidly
      degraded by the proteasome. In contrast, wild-type VHL proteins are directly
      stabilized by associating with both elongins B and C. In addition, elongins B and
      C are stabilized through their interactions with each other and VHL. Thus, the
      entire VHL/elongin complex is resistant to proteasomal degradation. Because the
      elongin-binding domain of VHL is frequently mutated in cancers, these results
      suggest that loss of elongin binding causes tumorigenesis by compromising VHL
      protein stability and/or potential VHL ubiquitination functions.

PMID- 10900012
TI  - Leptin, troglitazone, and the expression of sterol regulatory element binding
      proteins in liver and pancreatic islets.
AB  - Overaccumulation of lipids in nonadipose tissues of obese rodents may lead to
      lipotoxic complications such as diabetes. To assess the pathogenic role of the
      lipogenic transcription factor, sterol regulatory element binding protein 1
      (SREBP-1), we measured its mRNA in liver and islets of obese, leptin-unresponsive
      fa/fa Zucker diabetic fatty rats. Hepatic SREBP-1 mRNA was 2.4 times higher than
      in lean +/+ controls, primarily because of increased SREBP-1c expression. mRNA of
      lipogenic enzymes ranged from 2.4- to 4.6-fold higher than lean controls, and
      triacylglycerol (TG) content was 5.4 times higher. In pancreatic islets of fa/fa
      rats, SREBP-1c was 3.4 times higher than in lean +/+ Zucker diabetic fatty rats.
      The increase of SREBP-1 in liver and islets of untreated fa/fa rats was blocked
      by 6 weeks of troglitazone therapy, and the diabetic phenotype was prevented. Up
      regulation of SREBP-1 also occurred in livers of Sprague-Dawley rats with diet
      induced obesity. Hyperleptinemia, induced in lean +/+ rats by adenovirus gene
      transfer, lowered hepatic SREBP-1c by 74% and the lipogenic enzymes from 35 to
      59%. In conclusion, overnutrition increases and adenovirus-induced
      hyperleptinemia decreases SREBP-1c expression in liver and islets. SREBP-1
      overexpression, which is prevented by troglitazone, may play a role in the
      ectopic lipogenesis and lipotoxicity complicating obesity in Zucker diabetic
      fatty rats.

PMID- 10900014
TI  - Identification of eIF2Bgamma and eIF2gamma as cofactors of hepatitis C virus
      internal ribosome entry site-mediated translation using a functional genomics
      approach.
AB  - The 5'-untranslated region of hepatitis C virus (HCV) is highly conserved, folds
      into a complex secondary structure, and functions as an internal ribosome entry
      site (IRES) to initiate translation of HCV proteins. We have developed a
      selection system based on a randomized hairpin ribozyme gene library to identify
      cellular factors involved in HCV IRES function. A retroviral vector ribozyme
      library with randomized target recognition sequences was introduced into HeLa
      cells, stably expressing a bicistronic construct encoding the hygromycin B
      phosphotransferase gene and the herpes simplex virus thymidine kinase gene (HSV
      tk). Translation of the HSV-tk gene was mediated by the HCV IRES. Cells
      expressing ribozymes that inhibit HCV IRES-mediated translation of HSV-tk were
      selected via their resistance to both ganciclovir and hygromycin B. Two ribozymes
      reproducibly conferred the ganciclovir-resistant phenotype and were shown to
      inhibit IRES-mediated translation of HCV core protein but did not inhibit cap
      dependent protein translation or cell growth. The functional targets of these
      ribozymes were identified as the gamma subunits of human eukaryotic initiation
      factors 2B (eIF2Bgamma) and 2 (eIF2gamma), respectively. The involvement of
      eIF2Bgamma and eIF2gamma in HCV IRES-mediated translation was further validated
      by ribozymes directed against additional sites within the mRNAs of these genes.
      In addition to leading to the identification of cellular IRES cofactors,
      ribozymes obtained from this cellular selection system could be directly used to
      specifically inhibit HCV viral translation, thereby facilitating the development
      of new antiviral strategies for HCV infection.

PMID- 10900013
TI  - Epidermal growth factor-induced nuclear factor kappa B activation: A major
      pathway of cell-cycle progression in estrogen-receptor negative breast cancer
      cells.
AB  - The epidermal growth factor (EGF) family of receptors (EGFR) is overproduced in
      estrogen receptor (ER) negative (-) breast cancer cells. An inverse correlation
      of the level of EGFR and ER is observed between ER- and ER positive (+) breast
      cancer cells. A comparative study with EGFR-overproducing ER- and low-level
      producing ER+ breast cancer cells suggests that EGF is a major growth-stimulating
      factor for ER- cells. An outline of the pathway for the EGF-induced enhanced
      proliferation of ER- human breast cancer cells is proposed. The transmission of
      mitogenic signal induced by EGF-EGFR interaction is mediated via activation of
      nuclear factor kappaB (NF-kappaB). The basal level of active NF-kappaB in ER-
      cells is elevated by EGF and inhibited by anti-EGFR antibody (EGFR-Ab), thus
      qualifying EGF as a NF-kappaB activation factor. NF-kappaB transactivates the
      cell-cycle regulatory protein, cyclin D1, which causes increased phosphorylation
      of retinoblastoma protein, more strongly in ER- cells. An inhibitor of
      phosphatidylinositol 3 kinase, Ly294-002, blocked this event, suggesting a role
      of the former in the activation of NF-kappaB by EGF. Go6976, a well-characterized
      NF-kappaB inhibitor, blocked EGF-induced NF-kappaB activation and up-regulation
      of cell-cycle regulatory proteins. This low molecular weight compound also caused
      apoptotic death, predominantly more in ER- cells. Thus Go6976 and similar NF
      kappaB inhibitors are potentially novel low molecular weight therapeutic agents
      for treatment of ER- breast cancer patients.

PMID- 10900015
TI  - Calcium imaging demonstrates colocalization of calcium influx and extrusion in
      fly photoreceptors.
AB  - During illumination, Ca(2+) enters fly photoreceptor cells through light
      activated channels that are located in the rhabdomere, the compartment
      specialized for phototransduction. From the rhabdomere, Ca(2+) diffuses into the
      cell body. We visualize this process by rapidly imaging the fluorescence in a
      cross section of a photoreceptor cell injected with a fluorescent Ca(2+)
      indicator in vivo. The free Ca(2+) concentration in the rhabdomere shows a very
      fast and large transient shortly after light onset. The free Ca(2+) concentration
      in the cell body rises more slowly and displays a much smaller transient. After
      approximately 400 ms of light stimulation, the Ca(2+) concentration in both
      compartments reaches a steady state, indicating that thereafter an amount of
      Ca(2+), equivalent to the amount of Ca(2+) flowing into the cell, is extruded.
      Quantitative analysis demonstrates that during the steady state, the free Ca(2+)
      concentration in the rhabdomere and throughout the cell body is the same. This
      shows that Ca(2+) extrusion takes place very close to the location of Ca(2+)
      influx, the rhabdomere, because otherwise gradients in the steady-state
      distribution of Ca(2+) should be measured. The close colocalization of Ca(2+)
      influx and Ca(2+) extrusion ensures that, after turning off the light, Ca(2+)
      removal from the rhabdomere is faster than from the cell body. This is
      functionally significant because it ensures rapid dark adaptation.

PMID- 10900016
TI  - Calsenilin reverses presenilin-mediated enhancement of calcium signaling.
AB  - Most cases of autosomal-dominant familial Alzheimer's disease are linked to
      mutations in the presenilin genes (PS1 and PS2). In addition to modulating beta
      amyloid production, presenilin mutations also produce highly specific and
      selective alterations in intracellular calcium signaling. Although the molecular
      mechanisms underlying these changes are not known, one candidate molecular
      mediator is calsenilin, a recently identified calcium-binding protein that
      associates with the C terminus of both PS1 and PS2. In this study, we
      investigated the effects of calsenilin on calcium signaling in Xenopus oocytes
      expressing either wild-type or mutant PS1. In this system, mutant PS1 potentiated
      the amplitude of calcium signals evoked by inositol 1,4,5-trisphosphate and also
      accelerated their rates of decay. We report that calsenilin coexpression reverses
      both of these potentially pathogenic effects. Notably, expression of calsenilin
      alone had no discernable effects on calcium signaling, suggesting that calsenilin
      modulates these signals by a mechanism independent of simple calcium buffering.
      Our findings further suggest that the effects of presenilin mutations on calcium
      signaling are likely mediated through the C-terminal domain, a region that has
      also been implicated in the modulation of beta-amyloid production and cell death.

PMID- 10900018
TI  - An initiator element mediates autologous downregulation of the human type A gamma
      -aminobutyric acid receptor beta 1 subunit gene.
AB  - The regulated expression of type A gamma-aminobutyric acid receptor (GABA(A)R)
      subunit genes is postulated to play a role in neuronal maturation,
      synaptogenesis, and predisposition to neurological disease. Increases in GABA
      levels and changes in GABA(A)R subunit gene expression, including decreased beta1
      mRNA levels, have been observed in animal models of epilepsy. Persistent exposure
      to GABA down-regulates GABA(A)R number in primary cultures of neocortical
      neurons, but the regulatory mechanisms remain unknown. Here, we report the
      identification of a TATA-less minimal promoter of 296 bp for the human GABA(A)R
      beta1 subunit gene that is neuron specific and autologously down-regulated by
      GABA. beta1 promoter activity, mRNA levels, and subunit protein are decreased by
      persistent GABA(A)R activation. The core promoter, 270 bp, contains an initiator
      element (Inr) at the major transcriptional start site. Three concatenated copies
      of the 10-bp Inr and its immediate 3' flanking sequence produce full neural
      specific activity that is down-regulated by GABA in transiently transfected
      neocortical neurons. Taking these results together with those of DNase I
      footprinting, electrophoretic mobility shift analysis, and 2-bp mutagenesis, we
      conclude that GABA-induced down-regulation of beta1 subunit mRNAs involves the
      differential binding of a sequence-specific basal transcription factor(s) to the
      Inr. The results support a transcriptional mechanism for the down-regulation of
      beta1 subunit GABA(A)R gene expression and raises the possibility that altered
      levels of sequence-specific basal transcription factors may contribute to
      neurological disorders such as epilepsy.

PMID- 10900017
TI  - The gamma-aminobutyric acid type A receptor (GABAAR)-associated protein GABARAP
      interacts with gephyrin but is not involved in receptor anchoring at the synapse.
AB  - gamma-Aminobutyric acid type A receptors (GABA(A)Rs) are ligand-gated chloride
      channels that exist in numerous distinct subunit combinations. At postsynaptic
      membrane specializations, different GABA(A)R isoforms colocalize with the tubulin
      binding protein gephyrin. However, direct interactions of GABA(A)R subunits with
      gephyrin have not been reported. Recently, the GABA(A)R-associated protein
      GABARAP was found to bind to the gamma2 subunit of GABA(A)Rs. Here we show that
      GABARAP interacts with gephyrin in both biochemical assays and transfected cells.
      Confocal analysis of neurons derived from wild-type and gephyrin-knockout mice
      revealed that GABARAP is highly enriched in intracellular compartments, but not
      at gephyrin-positive postsynaptic membrane specializations. Our data indicate
      that GABARAP-gephyrin interactions are not important for postsynaptic GABA(A)R
      anchoring but may be implicated in receptor sorting and/or targeting mechanisms.
      Consistent with this idea, a close homolog of GABARAP, p16, has been found to
      function as a late-acting intra-Golgi transport factor.

PMID- 10900019
TI  - Dynamic regulation of neuronal NO synthase transcription by calcium influx
      through a CREB family transcription factor-dependent mechanism.
AB  - Neuronal nitric oxide (NO) synthase (nNOS) is dynamically regulated in response
      to a variety of physiologic and pathologic stimuli. Although the dynamic
      regulation of nNOS is well established, the molecular mechanisms by which such
      diverse stimuli regulate nNOS expression have not yet been identified. We
      describe experiments demonstrating that Ca(2+) entry through voltage-sensitive
      Ca(2+) channels regulates nNOS expression through alternate promoter usage in
      cortical neurons and that nNOS exon 2 contains the regulatory sequences that
      respond to Ca(2+). Deletion and mutational analysis of the nNOS exon 2 promoter
      reveals two critical cAMP/Ca(2+) response elements (CREs) that are immediately
      upstream of the transcription start site. CREB binds to the CREs within the nNOS
      gene. Mutation of the nNOS CREs as well as blockade of CREB function results in a
      dramatic loss of nNOS transcription. These findings suggest that nNOS is a Ca(2+)
      regulated gene through the interactions of CREB on the CREs within the nNOS exon
      2 promoter and that these interactions are likely to be centrally involved in the
      regulation of nNOS in response to neuronal injury and activity-dependent
      plasticity.

PMID- 10900020
TI  - Physiological astrocytic calcium levels stimulate glutamate release to modulate
      adjacent neurons.
AB  - Astrocytes can release glutamate in a calcium-dependent manner and consequently
      signal to adjacent neurons. Whether this glutamate release pathway is used during
      physiological signaling or is recruited only under pathophysiological conditions
      is not well defined. One reason for this lack of understanding is the limited
      knowledge about the levels of calcium necessary to stimulate glutamate release
      from astrocytes and about how they compare with the range of physiological
      calcium levels in these cells. We used flash photolysis to raise internal calcium
      in astrocytes, while monitoring astrocytic calcium levels and glutamate, which
      evoked slow inward currents that were recorded electrophysiologically from single
      neurons grown on microislands of astrocytes. With this approach, we demonstrate
      that modest changes of astrocytic calcium, from 84 to 140 nM, evoke substantial
      glutamatergic currents in neighboring neurons (-391 pA), with a Hill coefficient
      of 2.1 to 2.7. Because the agonists glutamate, norepinephrine, and dopamine all
      raise calcium in astrocytes to levels exceeding 1.8 microM, these quantitative
      studies demonstrate that the astrocytic glutamate release pathway is engaged at
      physiological levels of internal calcium. Consequently, the calcium-dependent
      release of glutamate from astrocytes functions within an appropriate range of
      astrocytic calcium levels to be used as a signaling pathway within the functional
      nervous system.

PMID- 10900021
TI  - Pentameric assembly of a neuronal glutamate transporter.
AB  - Freeze-fracture electron microscopy was used to study the structure of a human
      neuronal glutamate transporter (EAAT3). EAAT3 was expressed in Xenopus laevis
      oocytes, and its function was correlated with the total number of transporters in
      the plasma membrane of the same cells. Function was assayed as the maximum charge
      moved in response to a series of transmembrane voltage pulses. The number of
      transporters in the plasma membrane was determined from the density of a distinct
      10-nm freeze-fracture particle, which appeared in the protoplasmic face only
      after EAAT3 expression. The linear correlation between EAAT3 maximum carrier
      mediated charge and the total number of the 10-nm particles suggested that this
      particle represented functional EAAT3 in the plasma membrane. The cross-sectional
      area of EAAT3 in the plasma membrane (48 +/- 5 nm(2)) predicted 35 +/- 3
      transmembrane alpha-helices in the transporter complex. This information along
      with secondary structure models (6-10 transmembrane alpha-helices) suggested an
      oligomeric state for EAAT3. EAAT3 particles were pentagonal in shape in which
      five domains could be identified. They exhibited fivefold symmetry because they
      appeared as equilateral pentagons and the angle at the vertices was 110 degrees.
      Each domain appeared to contribute to an extracellular mass that projects
      approximately 3 nm into the extracellular space. Projections from all five
      domains taper toward an axis passing through the center of the pentagon, giving
      the transporter complex the appearance of a penton-based pyramid. The pentameric
      structure of EAAT3 offers new insights into its function as both a glutamate
      transporter and a glutamate-gated chloride channel.

PMID- 10900023
TI  - Dissociation of response conflict, attentional selection, and expectancy with
      functional magnetic resonance imaging.
AB  - Two different attentional networks have been associated with visuospatial
      attention and conflict resolution. In most situations either one of the two
      networks is active or both are increased in activity together. By using
      functional magnetic resonance imaging and a flanker task, we show conditions in
      which one network (anterior attention system) is increased in activity whereas
      the other (visuospatial attention system) is reduced, showing that attentional
      conflict and selection are separate aspects of attention. Further, we distinguish
      between neural systems involved in different forms of conflict. Specifically, we
      dissociate patterns of activity in the basal ganglia and insula cortex during
      simple violations in expectancies (i.e., sudden changes in the frequency of an
      event) from patterns of activity in the anterior attention system specifically
      correlated with response conflict as evidenced by longer response latencies and
      more errors. These data provide a systems-level approach in understanding
      integrated attentional networks.

PMID- 10900022
TI  - gamma-aminobutyric acid type B receptors are expressed and functional in
      mammalian cardiomyocytes.
AB  - gamma-Hydroxybutyrate (GHB), an anesthetic adjuvant analog of gamma-aminobutyrate
      (GABA), depresses cell excitability in hippocampal neurons by inducing
      hyperpolarization through the activation of a prominent inwardly rectifying K(+)
      (Kir3) conductance. These GABA type B (GABA(B))-like effects are clearly shown at
      high concentrations of GHB corresponding to blood levels usually reached during
      anesthesia and are mimicked by the GABA(B) agonist baclofen. Recent studies of
      native GABA(B) receptors (GABA(B)Rs) have favored the concept that GHB is also a
      selective agonist. Furthermore, cloning has demonstrated that GABA(B)Rs assemble
      heteromeric complexes from the GABA(B)R1 and GABA(B)R2 subtypes and that these
      assemblies are activated by GHB. The surprisingly high tissue content, together
      with anti-ischemic and protective effects of GHB in the heart, raises the
      question of a possible influence of GABA(B) agonists on excitable cardiac cells.
      In the present study, we provide electrophysiological evidence that GHB activates
      an inwardly rectifying K(+) current in rat ventricular myocytes. This effect is
      mimicked by baclofen, reversibly inhibited by GABA(B) antagonists, and prevented
      by pertussis toxin pretreatment. Both GABA(B)R1 and GABA(B)R2 are detected in
      cardiomyocytes by Western blotting and are shown to coimmunoprecipitate. Laser
      scanning confocal microscopy discloses an even distribution of the two receptors
      in the sarcolemma and along the transverse tubular system. Hence, we conclude
      that GABA(B)Rs are distributed not only in neuronal tissues but also in the
      heart, where they can be activated and induce electrophysiological alterations
      through G-protein-coupled inward rectifier potassium channels.

PMID- 10900024
TI  - Increased discrimination of "false memories" in autism spectrum disorder.
AB  - Individuals with autism spectrum disorder (ASD) have impaired ability to use
      context, which may manifest as alterations of relatedness within the semantic
      network. However, impairment in context use may be more difficult to detect in
      high-functioning adults with ASD. To test context use in this population, we
      examined the influence of context on memory by using the "false memory" test. In
      the false memory task, lists of words were presented to high-functioning subjects
      with ASD and matched controls. Each list consists of words highly related to an
      index word not on the list. Subjects are then given a recognition test. Positive
      responses to the index words represent false memories. We found that individuals
      with ASD are able to discriminate false memory items from true items
      significantly better than are control subjects. Memory in patients with ASD may
      be more accurate than in normal individuals under certain conditions. These
      results also suggest that semantic representations comprise a less distributed
      network in high-functioning adults with ASD. Furthermore, these results may be
      related to the unusually high memory capacities found in some individuals with
      ASD. Research directed at defining the range of tasks performed superiorly by
      high-functioning individuals with ASD will be important for optimal vocational
      rehabilitation.

PMID- 10900025
TI  - In the beginning: genome recognition, RNA encapsidation and the initiation of
      complex retrovirus assembly.

PMID- 10900026
TI  - The long terminal repeat is a determinant of cell tropism of maedi-visna virus.
AB  - Maedi-visna virus (MVV) is a lentivirus of sheep, mainly affecting the lungs and
      the central nervous system. Long terminal repeat (LTR) sequence variability is
      common in tissue culture-derived isolates of MVV as well as those of other
      lentiviruses. The role of this sequence variation in MVV replication has not been
      explored. PCR amplification of the LTRs of an MVV isolate revealed two product
      sizes, the larger containing a 53 bp duplication. PCR products containing the two
      size variants of the LTRs were cloned into an infectious molecular clone of MVV
      and the resulting chimeric viruses were tested for growth in various cell types.
      The chimeric virus containing only one copy of the 53 bp sequence was found to
      grow more slowly in sheep choroid plexus cells, sheep fibroblasts and sheep
      synovial cells than the virus with the 53 bp duplication. Both viruses grew
      equally well in macrophages. These results indicate that the LTRs determined the
      extended cell tropism of MVV.

PMID- 10900027
TI  - Destruction of primary CD4(+) T cells by cell-cell interaction in human
      immunodeficiency virus type 1 infection in vitro.
AB  - Infection of CD4(+) T lymphocytes with human immunodeficiency virus (HIV) in
      vitro is accompanied by extensive cytopathicity. The mechanism of cell death is
      unclear, but may be related to expression of the viral envelope glycoprotein.
      Here, it is demonstrated that T cell destruction in primary T cells occurs upon
      contact of infected with uninfected lymphocytes. Cell death was due to the
      interaction of the envelope glycoprotein with CD4 and subsequent fusion of the
      cells. Agents that interfered with cell-to-cell fusion such as a monoclonal
      antibody to CD4 and the peptide T20 prevented T cell death and depletion. In
      contrast, single-cell lysis due to expression and intracellular processing of the
      envelope glycoprotein was insignificant. These results suggest that cell-to-cell
      fusion and concomitant rapid cell death promote the depletion of T cells in HIV
      infected individuals.

PMID- 10900028
TI  - Sequence motifs required for lipid droplet association and protein stability are
      unique to the hepatitis C virus core protein.
AB  - From analysis of the primary sequence of the hepatitis C virus (HCV) core
      protein, we have identified three separable regions based on hydrophobicity and
      clustering of basic amino acids within the protein. Comparison with capsid
      proteins of related pesti- and flaviviruses suggested that HCV core has a unique
      central domain (domain 2). Previous findings have revealed that core protein can
      associate with lipid droplets which are intracellular storage sites for
      triacylglycerols and cholesterol esters. Confocal analysis of variant forms
      lacking regions of core indicated that most residues within the unique region are
      necessary for association of the protein with lipid droplets. A segment within
      domain 2 (from residues 125 to 144) also was required for stability of the
      protein and a polypeptide lacking these sequences was degraded apparently by the
      proteasome. In cells depleted of lipid droplets, core protein remained located in
      the cytoplasm. Moreover, cleavage of the protein at the maturation site and
      stability were not affected by inability to bind to lipid droplets.

PMID- 10900029
TI  - Isolation of Hendra virus from pteropid bats: a natural reservoir of Hendra
      virus.
AB  - Since it was first described in Australia in 1994, Hendra virus (HeV) has caused
      two outbreaks of fatal disease in horses and humans, and an isolated fatal horse
      case. Our preliminary studies revealed a high prevalence of neutralizing
      antibodies to HeV in bats of the genus PTEROPUS:, but it was unclear whether this
      was due to infection with HeV or a related virus. We developed the hypothesis
      that HeV excretion from bats might be related to the birthing process and we
      targeted the reproductive tract for virus isolation. Three virus isolates were
      obtained from the uterine fluid and a pool of foetal lung and liver from one grey
      headed flying-fox (Pteropus poliocephalus), and from the foetal lung of one black
      flying-fox (P. alecto). Antigenically, these isolates appeared to be closely
      related to HeV, returning positive results on immunofluorescent antibody staining
      and constant-serum varying-virus neutralization tests. Using an HeV-specific
      oligonucleotide primer pair, genomic sequences of the isolates were amplified.
      Sequencing of 200 nucleotides in the matrix gene identified that these three
      isolates were identical to HeV. Isolations were confirmed after RNA extracted
      from original material was positive for HeV RNA when screened on an HeV Taqman
      assay. The isolation of HeV from pteropid bats corroborates our earlier
      serological and epidemiological evidence that they are a natural reservoir host
      of the virus.

PMID- 10900030
TI  - Phylogenetic analysis of influenza C virus nonstructural (NS) protein genes and
      identification of the NS2 protein.
AB  - The nucleotide sequences of RNA segment 7 (nonstructural protein gene; NS) were
      compared among 34 influenza C virus strains isolated between 1947 and 1992. The
      results showed that all the NS genes analysed had the potential to encode NS1 and
      NS2 proteins of 246 and 182 amino acids, respectively. The deduced amino acid
      sequence of the previously unidentified NS2 was fairly well conserved, although
      it was more divergent than the NS1 protein sequence. Moreover,
      immunoprecipitation experiments with rabbit immune serum against a glutathione S
      transferase fusion protein containing the C-terminal region of the 182 amino acid
      NS2 protein revealed synthesis of a protein with an apparent molecular mass of
      approximately 22 kDa in infected cells. A phylogenetic analysis showed that the
      34 NS genes were split into two distinct groups, A and B. Comparison of the
      phylogenetic positions of the individual isolates in the NS gene tree with those
      in the haemagglutinin-esterase (HE) gene tree suggested that most of the
      influenza C viruses currently circulating in Japan, irrespective of their HE gene
      lineage, had acquired group B NS genes through reassortment events that
      presumably occurred either in the 1970s or in the early 1980s.

PMID- 10900031
TI  - Rescue of synthetic salmonid rhabdovirus minigenomes.
AB  - Synthetic T7-driven cDNA minigenomes containing the bacterial chloramphenicol
      acetyltransferase gene as a reporter were derived from the genome of two salmonid
      novirhabdoviruses, infectious haematopoietic necrosis virus (IHNV) and viral
      haemorrhagic septicaemia virus (VHSV). We showed that an exogenous IHNV RNA
      minigenome transfected into fish cells could be rescued following IHNV infection
      as it was replicated, encapsidated and transcribed. When cells were infected with
      a recombinant vaccinia virus expressing T7 RNA polymerase (vTF7-3), transfected
      with the plasmid carrying the IHNV minigenome (genomic- and antigenomic-sense)
      and superinfected with IHNV, rescue of the minigenome was more efficient.
      Heterologous VHSV/IHNV rescue experiments failed. Finally, when the IHNV N, P and
      L proteins were expressed from cDNAs in cells, the minigenome was also
      successfully rescued, indicating that the nucleocapsid proteins were biologically
      functional. These data represent the first example of rescue experiments for non
      mammalian rhabdoviruses replicating at a low temperature.

PMID- 10900032
TI  - Authentic Borna disease virus transcripts are spliced less efficiently than cDNA
      derived viral RNAs.
AB  - Borna disease virus (BDV) is a non-segmented, negative-strand RNA virus that
      replicates and transcribes its genome in the nucleus of infected cells. It uses
      the cellular splicing machinery to generate a set of alternatively spliced mRNAs
      from the 2.8 and 7.1 kb primary transcripts, each harbouring two introns. To
      determine whether splicing of these transcripts is regulated by viral factors,
      the extent of splicing was studied in infected cells and COS-7 cells transiently
      transfected with plasmids encoding the 2.8 kb RNA of BDV. Unspliced RNA was found
      to be the most abundant RNA species in infected cells, whereas viral transcripts
      lacking both introns were only found in minute amounts. In sharp contrast,
      plasmid-derived 2.8 kb RNA was predominantly intron 1-spliced and double-spliced.
      Co-expression of the BDV proteins P, N and X did not influence splicing of
      plasmid-expressed 2.8 kb RNA. Furthermore, the splicing pattern did not change
      when the 2.8 kb RNA was expressed in BDV-infected cells. Based on these results
      we speculate that splicing of authentic BDV transcripts is tightly linked to
      transcription by the viral polymerase.

PMID- 10900033
TI  - Membrane-destabilizing activity of rotavirus NSP4 is mediated by a membrane
      proximal amphipathic domain.
AB  - Expression of the rotavirus non-structural glycoprotein NSP4 in E. coli leads to
      a decrease in optical density of the culture and release of [(3)H]uridine into
      the medium, effects attributable to the ability of NSP4 to perturb the bacterial
      membrane. To identify a domain of NSP4 responsible, different regions of the
      polypeptide were expressed in E. coli. Membrane destabilization is associated
      with a region of the protein located within residues 48-91, which includes a
      potential cationic amphipathic helix. A second region of NSP4 that contains a
      coiled-coil oligomerization domain and a sequence reported to function as a viral
      enterotoxin enhances the membrane-destabilizing activity of residues 48-91, but
      has no direct effect on the membrane stability. These studies suggest that the
      membrane-destabilizing and enterotoxic properties of NSP4 may be mediated by
      different regions of the polypeptide and suggest a possible basis for the
      cytotoxicity of NSP4 in mammalian cells.

PMID- 10900034
TI  - NTP binding and phosphohydrolase activity associated with purified bluetongue
      virus non-structural protein NS2.
AB  - The bluetongue virus ssRNA-binding protein, NS2, is a phosphoprotein that forms
      viral inclusion bodies in infected cells. Recombinant NS2 was expressed in the
      baculovirus expression system and purified to homogeneity from insect cells.
      Purified NS2 bound nucleosides. Further investigation revealed that the protein
      bound ATP and GTP and could hydrolyse both nucleosides to their corresponding
      NMPs, with a higher efficiency for the hydrolysis of ATP. The increased
      efficiency of hydrolysis of ATP correlated with a higher binding affinity of NS2
      for ATP than GTP. Ca(2+), Mg(2+) and Mn(2+) were able to function as the required
      divalent cation in the reactions. The phosphohydrolase activity was not sensitive
      to ouabain, an inhibitor of cellular ATPases, suggesting that this activity was
      not the result of a cellular contaminant.

PMID- 10900035
TI  - Polyomavirus persistence in lymphocytes: prevalence in lymphocytes from blood
      donors and healthy personnel of a blood transfusion centre.
AB  - BK and JC polyomaviruses (BKV and JCV) are widespread in humans and are thought
      to persist and reactivate under immune alterations. In addition to the kidney,
      lymphoid cells have been proposed as a site of latency. However, while this was
      shown to occur in immunocompromised patients, discordant data were published for
      healthy humans. To help to solve this issue, an extensive study (231 healthy
      subjects) was carried out on peripheral blood mononuclear cells (PBMC) from blood
      donors of two towns and from operators of a blood transfusion centre. To
      discriminate between past and recent infection, nested PCRs for BKV and JCV non
      coding control region (NCCR) and VP1 DNA sequences were carried out. Twenty-two
      per cent of subjects had BKV NCCR, but only 7% also had BKV VP1, as detected by
      PCR assays of similar sensitivities; the latter positivity was found to decrease
      with age. In both towns, the BKV WW archetypal DDP strain, subtype I, was found.
      Only 0.9% of subjects contained JCV DNA, for both NCCR and VP1. Blood operators
      presented a statistically significant increased prevalence of BKV NCCR (3. 0
      fold) and BKV VP1 (9.4-fold) sequences with respect to blood donors of comparable
      ages, suggesting the possibility of occupational risk of BKV (re)infection or
      reactivation. Since the possibility of amplifying BKV VP1 sequences from PBMC of
      healthy humans is lost with age, this suggests that PBMC are not a site of
      polyomavirus persistence in healthy individuals and that detection of BKV VP1 DNA
      in PBMC is probably indicative of recent infection or reactivation.

PMID- 10900036
TI  - Sequence analysis of the long control region of human papillomavirus type 16
      variants and functional consequences for P97 promoter activity.
AB  - Genital human papillomaviruses (HPV) are considered to be one of the main risk
      factors for the development of cervical cancer. The P97 promoter at the E6
      proximal end of the long control region (LCR) regulates the transcription of
      viral genes, especially the oncogenes E6 and E7. The LCR contains binding sites
      of several viral and cellular transcription factors, which either activate or
      repress the P97 promoter. Intratype variants of HPV-16 belong to six
      geographically clustered phylogenetic groups distributed all over the world.
      These variants exhibit differences in E6 protein activities and in tumour
      progression in vivo. Seven HPV-16 variants were investigated by sequencing the
      entire LCR (nt 7060-124) and by comparing the transcriptional activities of their
      P97 promoters. Previously unknown nucleotide variations were identified in all
      LCRs investigated. In luciferase assays, 3.3- and 2.8-fold increases in P97
      promoter activity were detected in the Asian American c and North American 1
      variants when compared with the European reference clone. The African variants 1a
      and 2a exhibited P97 promoter activities comparable to the European reference
      clone. After recombining different LCR fragments, the region responsible for
      enhanced transcription in the Asian American c and North American 1 variants
      could be attributed to the E6-proximal end of the LCR (nt 7619-124).

PMID- 10900037
TI  - Distinct patterns of alteration of myc genes associated with integration of human
      papillomavirus type 16 or type 45 DNA in two genital tumours.
AB  - We previously described two genital carcinomas (IC2, IC4) containing human
      papillomavirus type 16 (HPV-16)- or HPV-18-related sequences integrated in
      chromosomal bands containing the c-myc (8q24) or N-myc (2p24) gene, respectively.
      The c-myc gene was rearranged and amplified in IC2 cells without evidence of
      overexpression. The N-myc gene was amplified and highly transcribed in IC4 cells.
      Here, the sequence of an 8039 bp IC4 DNA fragment containing the integrated viral
      sequences and the cellular junctions is reported. A 3948 bp segment of the genome
      of HPV-45 encompassing the upstream regulatory region and the E6 and E7 ORFs was
      integrated into the untranslated part of N-myc exon 3, upstream of the N-myc
      polyadenylation signal. Both N-myc and HPV-45 sequences were amplified 10- to 20
      fold. The 3' ends of the major N-myc transcript were mapped upstream of the 5'
      junction. A minor N-myc/HPV-45 fusion transcript was also identified, as well as
      two abundant transcripts from the HPV-45 E6-E7 region. Large amounts of N-myc
      protein were detected in IC4 cells. A major alteration of c-myc sequences in IC2
      cells involved the insertion of a non-coding sequence into the second intron and
      their co-amplification with the third exon, without any evidence for the
      integration of HPV-16 sequences within or close to the gene. Different patterns
      of myc gene alterations may thus be associated with integration of HPV DNA in
      genital tumours, including the activation of the protooncogene via a mechanism of
      insertional mutagenesis and/or gene amplification.

PMID- 10900039
TI  - Transcriptional regulation of the channel catfish virus genome direct repeat
      region.
AB  - Channel catfish virus (CCV), a member of the herpesvirus family, causes a severe
      haemorrhagic disease in juvenile channel catfish. In this report, we confirm that
      CCV gene expression is temporally regulated into immediate-early (IE), early and
      late phases, similar to that of other herpesviruses. The transcriptional
      regulation of the 14 genes within the direct repeat region of the CCV genome was
      determined by Northern hybridization analysis of RNA isolated from infected cells
      in the presence or absence of metabolic inhibitors. Two CCV genes within the
      direct repeat, ORFs 1 and 3, expressed IE transcripts. Early RNAs were encoded by
      ORFs 2-9 and 11-14. ORFs 4, 7 and 10-13 expressed late transcripts after the
      onset of viral DNA replication. A time-course study conducted without metabolic
      inhibitors confirmed that CCV direct repeat transcription is temporally
      regulated. The characterization of CCV transcription during cytolytic infection
      in vitro will provide a foundation for the analysis of CCV gene expression in
      tissues of acutely and latently infected catfish.

PMID- 10900038
TI  - Contribution of bovine papillomavirus type 1 E1 protein residue 48 to replication
      function.
AB  - The E1 protein of bovine papillomavirus type 1 (BPV-1) is the origin recognition
      protein and is essential for the initiation of viral DNA replication. We reported
      previously that there is a conserved motif between residues 25 and 60 of all
      papillomavirus E1 proteins that resembles a casein kinase II (CKII)
      phosphorylation site. The corresponding serine in BPV-1, serine-48, is an
      efficient substrate for CKII in vitro. To examine the functional role of this
      potential phosphorylation site, three amino acid substitutions were constructed
      at serine-48. Conversion of serine-48 to a glycine (S48G) resulted in a BPV-1
      genome that was unable to replicate and had reduced transformation capacity. The
      S48G E1 protein also failed to support replication of a BPV-1 origin-containing
      plasmid when expressed from a heterologous vector rather than the viral genome,
      indicating a direct replication defect. In contrast, conversion of serine-48 to
      acidic residues (S48D or S48E), which mimic the charge and structure of
      phosphoserine, maintained the wild-type replication phenotype. These mutational
      results are consistent with a replication requirement for a negative charge at
      serine-48, presumably supplied by in vivo phosphorylation. The mechanistic basis
      for the negative charge requirement was examined by testing several activities of
      the S48G mutant E1 protein in vivo using yeast one- and two-hybrid systems. No
      gross defect was observed for stability, origin binding or interaction with E2 or
      for E1-E1 interaction, although subtle defects in these activities would not
      likely be detected. Overall, the results suggest that important phosphoregulatory
      control of E1 replication function is mediated through the N-terminal region of
      this protein.

PMID- 10900040
TI  - Natural infection with herpes simplex virus type 1 (HSV-1) induces humoral and T
      cell responses to the HSV-1 glycoprotein H:L complex.
AB  - The glycoproteins of herpes simplex virus type 1 (HSV-1) are important targets
      for the immune system in the control of HSV-1 infections. The humoral and T cell
      responses to the glycoprotein (g)H(t(His)):gL complex of HSV-1 were studied in
      seven HSV-1-seropositive and three HSV-1-seronegative healthy adults. In
      addition, responses to HSV-1 gD(t) were determined. As antigens, purified soluble
      recombinant forms of the gH(t(His)):gL complex produced by insect cells and of
      gD(t) produced by yeast cells were used. In contrast to seronegative donors, sera
      of all seropositive donors contained gH(t(His)): gL-specific IgG. Using
      peripheral blood (PB) T cells, gH(t(His)):gL-specific proliferative T cell
      responses were detected in all seropositive donors. Culture supernatants of PB T
      cells stimulated with recombinant gH(t(His)):gL contained high levels of
      interferon-gamma and no detectable interleukin-4, indicating their Th1 phenotype.
      These results show that naturally acquired HSV-1 infection induces gH:gL-specific
      humoral and T cell responses.

PMID- 10900041
TI  - Characterization of cell-cell fusion mediated by herpes simplex virus 2
      glycoproteins gB, gD, gH and gL in transfected cells.
AB  - The mechanisms by which herpes simplex viruses (HSV) mediate fusion between their
      envelope and the plasma membrane during entry into cells, and between the plasma
      membranes of adjacent infected and uninfected cells to form multinucleated giant
      cells, are poorly understood. Four viral glycoproteins (gB, gD, gH and gL) are
      required for virus-cell fusion, whereas these plus several others are required
      for cell-cell fusion (syncytium formation). A better understanding would be aided
      by the availability of a model system, whereby fusion could be induced with a
      minimal set of proteins, in the absence of infection. A suitable system has now
      been developed for HSV-2, using transfected COS7, 293 or HEp-2 cells. Insofar as
      the minimal set of HSV-2 proteins required to cause cell-cell fusion in this
      system is gB, gD, gH and gL, it would appear to resemble virus-cell fusion rather
      than syncytium formation. However, the ability of a mutation in gB to enhance the
      fusion of both transfected cells and infected cells, while having no effect on
      virus-cell fusion, points to the opposite conclusion. The differential effects of
      a panel of anti-HSV antibodies, and of the fusion-inhibitor cyclosporin A,
      confirm that the fusion of transfected cells shares some properties with virus
      cell fusion and others with syncytium formation. It may therefore prove useful
      for determining how these processes differ, and for testing the hypothesis that
      some viral proteins prevent membrane fusion until the appropriate point in the
      virus life-cycle, with other proteins then overcoming this block.

PMID- 10900042
TI  - Phylogenetic analysis of human herpesvirus-8 in South Africa and identification
      of a novel subgroup.
AB  - The incidence of Kaposi's sarcoma in South Africa is increasing in parallel with
      the human immunodeficiency virus type 1 epidemic. An 804 bp region in the ORF75
      gene of 40 human herpesvirus-8 (HHV-8) isolates from South Africa was sequenced
      and the phylogenetic relationships were compared to published sequences. Nineteen
      strains clustered with subgroup B and 11 with subgroup A; however, the bootstrap
      values supporting these subgroups were not significant. Three strains grouped
      significantly with the C subgroup, while eight sequences did not cluster with any
      of the previously classified subgroups and were termed novel (N). The N subgroup
      differed from the A, B and C subgroups by DNA distances of 4.8, 4.2 and 4.5%,
      respectively, although within the N subgroup there was only 0.4% variation. The
      inclusion of this subgroup increased the number of previously described subgroup
      specific polymorphisms from 17 to 47 over an 804 bp region. There was sufficient
      inter-subgroup genetic diversity for a single-strand conformational polymorphism
      assay to be used to identify them rapidly. Thus, based on analysis of the ORF75
      gene, a unique HHV-8 subgroup, termed N, is present in South Africa, which
      accounts for 20% of circulating strains. Further studies are required to
      determine the degree of genetic divergence, distribution and pathogenic potential
      of this novel subgroup.

PMID- 10900043
TI  - On the control of late gene expression in Kaposi's sarcoma-associated herpesvirus
      (human herpesvirus-8).
AB  - Herpesvirus late genes require viral DNA replication for maximal expression.
      Although late gene expression appears to require DNA replication in cis in
      alphaherpesviruses, studies in Epstein-Barr virus (EBV) suggest that this cis
      requirement might not pertain to the gammaherpesviruses. Based on these findings,
      a system was created to investigate the elements required for the regulation of
      Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus-8) late gene
      expression. The transcript of a classic late gene encoding the viral assembly
      protein was characterized and reporter genes driven by the assembly protein
      promoter region were constructed. Unlike the EBV case, expression of a reporter
      gene under the control of the assembly protein promoter did not display authentic
      regulation when removed from the context of the viral genome. Although reporter
      expression rose in cells displaying lytic replication, this expression was not
      diminished by specific inhibitors of viral DNA synthesis. Minimal core promoters
      were similarly unable to reproduce late gene regulation. These results suggest
      that proper KSHV late gene expression is likely to be dependent upon virus lytic
      replication in cis and indicate that the regulation of KSHV late genes more
      closely resembles that observed in herpes simplex virus than that described for
      EBV.

PMID- 10900044
TI  - Hot-spot variations of Kaposi's sarcoma-associated herpesvirus latent nuclear
      antigen and application in genotyping by PCR-RFLP.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus-8) is
      aetiologically associated with Kaposi's sarcoma and several other
      lymphoproliferative disorders. The latent nuclear antigen (LNA) encoded by KSHV
      ORF73 has important functions in virus latent infection and shows molecular
      polymorphism. Sequence variations were identified in the internal repeat domain
      (IRD) of ORF73. DNA sequencing of ORF73 from one KSHV-infected cell line, PK-1,
      revealed that there were 558 bp (30.2%) deletions and 66 (3.6%) point mutations
      located mainly in repeat region 2, the glutamine-rich region of ORF73 IRD,
      compared with ORF73 of BC-1 KSHV. Similar sequence variations of ORF73 were also
      identified in two other isolates. None of the sequence variations caused any
      translational frame-shift in these four KSHV isolates examined, suggesting that
      LNA has a conservative function in virus latent infection. The frequent sequence
      variations in repeat region 2 of ORF73 IRD were also identified by PCR-RFLP
      genotyping in 26 KSHV isolates, suggesting that this region is a 'hot-spot' for
      genetic variations. Each Kaposi's sarcoma lesion sample contained one virus
      genotype with a unique RFLP pattern, indicating that in vivo KSHV infection was
      established with single predominate genotypes, which was further supported by the
      presence of invariable genotypes in multifocal lesions from individual KS
      patients. Four KSHV subtypes were classified based on the RFLP patterns that
      represent the patterns of DNA sequence variations in the ORF73 IRD. PCR-RFLP
      genotyping is capable of identifying LNA genetic variations and differentiating
      individual KSHV isolates, and thus may be useful for KSHV molecular epidemiology
      studies.

PMID- 10900045
TI  - Evidence that the first strand-transfer reaction of duck hepatitis B virus
      reverse transcription requires the polymerase and that strand transfer is not
      needed for the switch of the polymerase to the elongation mode of DNA synthesis.
AB  - Deletion of amino acids 79-88 in the duck hepatitis B virus reverse transcriptase
      had minimal effects on polymerase activities prior to the minus-strand DNA
      transfer reaction, yet it greatly diminished strand transfer and subsequent DNA
      synthesis. This mutation also reduced reverse transcription on exogenous RNA
      templates. The reaction on exogenous RNAs employed the phosphonoformic acid (PFA)
      sensitive elongation mode of DNA synthesis rather than the PFA-resistant priming
      mode, despite the independence of DNA synthesis in this assay from the priming
      and minus-strand transfer reactions. These data provide experimental evidence
      that the polymerase is involved directly in the minus-strand transfer reaction
      and that the switch of the polymerase from the early PFA-resistant mode of DNA
      synthesis to the later PFA-sensitive elongation mode does not require the strand
      transfer reaction.

PMID- 10900046
TI  - Distribution of chicken anaemia virus in the reproductive tissues of specific
      pathogen-free chickens.
AB  - The specific-pathogen-free (SPF) flocks of chickens maintained by the Department
      of Microbiology and Immunology at Cornell University became infected,
      inadvertently, with chicken anaemia virus (CAV), as demonstrated by
      seroconversion. Chickens from five flocks representing three different strains
      were examined for the presence of CAV using nested PCR. Virus was detected in
      ovaries, infundibula, vas deferentia, testes and spleens. Ovaries were positive
      in 38 to 72% of the hens in four flocks with 13 to 56 birds examined per flock.
      Interestingly, the ovaries were often the only positive tissues, while a few hens
      had only positive spleens. In roosters, the vas deferens was positive in 30 to
      79% of the birds with 5 to 19 birds examined per flock; the vas deferens was the
      only positive tissue in 20 to 37%. Individual cells in the theca externa and rare
      epithelial cells in the infundibular epithelium were positive for CAV by in situ
      PCR. Positive cells were not detected in testes or vas deferentia. The SH-1
      strain of CAV was isolated from these tissues and partially sequenced. Only minor
      sequence differences were found compared to CIA-1 and Cux-1. Embryos from matings
      between persistently infected dams and sire had CAV-positive cells in mesenchyme
      near the developing vertebral column. The data show that CAV persists in the
      reproductive tissues far longer than previously thought, and that it can be
      vertically transmitted from persistently infected birds.

PMID- 10900047
TI  - Adeno-associated virus (AAV)-3-based vectors transduce haematopoietic cells not
      susceptible to transduction with AAV-2-based vectors.
AB  - Although adeno-associated virus (AAV)-2 has a broad tissue-host range and can
      transduce a wide variety of tissue types, some cells, such as erythro
      megakaryoblastoid cells, are non-permissive and appear to lack the AAV-2
      receptor. However, limited studies have been reported with the related
      dependovirus AAV-3. We have previously cloned this virus, characterized its
      genome and produced an infectious clone. In this study, the gene for green
      fluorescent protein (GFP) was inserted into AAV-2- and AAV-3-based plasmids and
      recombinant viruses were produced. These viruses were then used to transduce
      haematopoietic cells and the transduction efficiencies were compared. In contrast
      to recombinant (r) AAV-2, rAAV-3 successfully transduced erythroid and
      megakaryoblastoid cells, although rAAV-2 was superior in transduction of
      lymphocyte-derived cell lines. Recently, it was reported that heparan sulphate
      can act as a receptor of AAV-2. The infectivity of rAAV-2 and rAAV-3 was tested
      with mutant cell lines of Chinese hamster ovary cells that were defective for
      heparin or heparan sulphate expression on the cell surface. There was no
      correlation between the ability of rAAV-2 or rAAV-3 to infect cells and the cell
      surface expression of heparan sulphate and, although heparin blocked both rAAV-2
      and rAAV-3 transduction, the ID(50) of rAAV-3 was higher than that of rAAV-2. In
      addition, virus-binding overlay assays indicated that AAV-2 and AAV-3 bound
      different membrane proteins. These results suggest not only that there are
      different cellular receptors for AAV-2 and AAV-3, but that rAAV-3 vectors may be
      preferred for transduction of some haematopoietic cell types.

PMID- 10900048
TI  - Intracellular distribution, cell-to-cell trafficking and tubule-inducing activity
      of the 50 kDa movement protein of Apple chlorotic leaf spot virus fused to green
      fluorescent protein.
AB  - The 50 kDa protein (50KP) encoded by ORF2 of Apple chlorotic leaf spot virus
      (ACLSV) fused to green fluorescent protein (GFP) was expressed transiently in
      cells of Nicotiana occidentalis and Chenopodium quinoa leaves. Its intracellular
      distribution, cell-to-cell trafficking in leaf epidermis and tubule formation on
      the surface of protoplasts were analysed. The 50KP-GFP fluorescence was
      distributed as small irregular spots or a fibrous network structure on the
      periphery of epidermal cells and protoplasts of both plant species. In leaf
      epidermis of N. occidentalis, the protein spread from the cells that produced it
      into neighbouring cells in both young and mature leaves and targetted
      plasmodesmata in these cells. In contrast, GFP was restricted to single cells in
      most cases in mature leaves. When 50KP and GFP were co-expressed in leaf
      epidermis of N. occidentalis, GFP spread more widely from the initial cells that
      produced it than when GFP was expressed alone, suggesting that 50KP facilitated
      the cell-to-cell trafficking of GFP. 50KP-GFP was able to complement local spread
      of 50KP-deficient virus when expressed transiently in leaf epidermis of C.
      quinoa. Expression of 50KP-GFP in protoplasts resulted in the production of
      tubular structures protruding from the surface. Mutational analyses showed that
      the C-terminal region (aa 287-457) was not essential for localization to
      plasmodesmata, cell-to-cell trafficking, complementation of movement of 50KP
      deficient virus or tubule formation on protoplasts. In contrast, deletions in the
      N-terminal region resulted in the complete disruption of all these activities.

PMID- 10900049
TI  - In vitro phosphorylation of the movement protein of tomato mosaic tobamovirus by
      a cellular kinase.
AB  - The movement protein (MP) of tomato mosaic virus (ToMV) was produced in E. coli
      as a soluble fusion protein with glutathione S-transferase. When immobilized on
      glutathione affinity beads, the recombinant protein was phosphorylated in vitro
      by incubating with cell extracts of Nicotiana tabacum and tobacco suspension
      culture cells (BY-2) in the presence of [gamma-(32)P]ATP. Phosphorylation
      occurred even after washing the beads with a detergent-containing buffer,
      indicating that the recombinant MP formed a stable complex with some protein
      kinase(s) during incubation with the cell extract. Phosphoamino acid analysis
      revealed that the MP was phosphorylated on serine and threonine residues.
      Phosphorylation of the MP was decreased by addition of kinase inhibitors such as
      heparin, suramin and quercetin, which are known to be effective for casein kinase
      II (CK II). The phosphorylation level was not changed by other types of
      inhibitor. In addition, as shown for animal and plant CK II, [gamma-(32)P]GTP was
      efficiently used as a phosphoryl donor. Phosphorylation was not affected by amino
      acid replacements at serine-37 and serine-238, but was completely inhibited by
      deletion of the carboxy-terminal 9 amino acids, including threonine-256, serine
      257, serine-261 and serine-263. These results suggest that the MP of ToMV could
      be phosphorylated in plant cells by a host protein kinase that is closely related
      to CK II.

PMID- 10900050
TI  - A single chimeric transgene derived from two distinct viruses confers multi-virus
      resistance in transgenic plants through homology-dependent gene silencing.
AB  - We showed previously that 218 and 110 bp N gene segments of tomato spotted wilt
      virus (TSWV) that were fused to the non-target green fluorescent protein (GFP)
      gene were able to confer resistance to TSWV via post-transcriptional gene
      silencing (PTGS). N gene segments expressed alone did not confer resistance.
      Apparently, the GFP DNA induced PTGS that targetted N gene segments and the
      incoming homologous TSWV for degradation, resulting in a resistant phenotype.
      These observations suggested that multiple resistance could be obtained by
      replacing the GFP DNA with a viral DNA that induces PTGS. The full-length coat
      protein (CP) gene of turnip mosaic virus (TuMV) was linked to 218 or 110 bp N
      gene segments and transformed into Nicotiana benthamiana. A high proportion (4 of
      18) of transgenic lines with the 218 bp N gene segment linked to the TuMV CP gene
      were resistant to both viruses, and resistance was transferred to R(2) plants.
      Nuclear run-on and Northern experiments confirmed that resistance was via PTGS.
      In contrast, only one of 14 transgenic lines with the TuMV CP linked to a 110 bp
      N gene segment yielded progeny with multiple resistance. Only a few R(1) plants
      were resistant and resistance was not observed in R(2) plants. These results
      clearly show the applicability of multiple virus resistance through the fusion of
      viral segments to DNAs that induce PTGS.

PMID- 10900052
TI  - Molecular analysis of Irish sheep scrapie cases.

PMID- 10900051
TI  - Analysis of the complete genome sequence of black queen-cell virus, a picorna
      like virus of honey bees.
AB  - A virus with picorna-like biophysical properties was isolated from South African
      honey bees. On the basis of serology, it was identified as an isolate of black
      queen-cell virus (BQCV). Nucleotide sequence analysis revealed an 8550 nt
      polyadenylated genome containing two large ORFs. The 5'-proximal ORF (ORF 1)
      represented 4968 nt while the 3'-proximal ORF (ORF 2) represented 2562 nt. The
      ORFs were separated by a 208 nt intergenic region and were flanked by a 657 nt 5'
      untranslated region and a 155 nt 3'-untranslated region. Deduced amino acid
      sequences for ORF 1 and ORF 2 were most similar to the non-structural and
      structural proteins, respectively, of Drosophila C virus (DCV), Rhopalosiphum
      padi virus (RhPV), Himetobi P virus (HiPV) and Plautia stali intestine virus
      (PSIV). It is proposed that BQCV belongs to the group of picorna-like, insect
      infecting RNA viruses constituted by DCV, RhPV, HiPV and PSIV.

PMID- 10900053
TI  - Photodynamic therapy of early squamous cell cancers of the esophagus.
AB  - The conventional treatment for the cure of esophageal cancer is surgical
      resection. Esophageal cancer, when detected at an early stage, has a very good
      probability of being eradicated by less aggressive procedures, and photodynamic
      therapy has proven to be a safe and effective treatment modality in some
      carefully selected patients. The indications, outcomes, and future considerations
      regarding the use of photodynamic therapy for the treatment of superficial
      squamous cell carcinomas of the esophagus are discussed in this article.

PMID- 10900054
TI  - Approach to patients who fail initial weaning trials.
AB  - Most patients who are recovering from respiratory failure are successfully
      liberated from mechanical ventilation easily and soon after the causative
      disorders are corrected. Roughly one third of patients, however, are not
      successful on initial attempts at liberation. Clinicians should define and treat
      the causes of respiratory failure and use validated methods to initiate weaning
      and manage patients who fail initial spontaneous breathing trials.

PMID- 10900055
TI  - Bernstein's failure to join the space race: his commentary on Tsiolkovskii's
      "Mechanics in Biology" (1964).
AB  - October 4, 1957, the Soviet Union launched Sputnik I into orbit from Tyuratam in
      Turkistan. An event "with the suddenness and surprise of a Pearl Harbor and of
      the impact of a Hiroshima atomic explosion" (Stoiko, 1970, p. ix). Nor would this
      be the only time America lost to the Russians in the space race. November 3 of
      the same year, Sputnik II carried the dog Laika, the first living being who
      traveled, and died, in space. In the USA, Senator Lyndon B. Johnson lamented:
      "Control of space means control of the world" (quoted from Heppenheimer, 1997, p.
      126), and attempts were made to speed up Wernher von Braun's launching program
      (Piszkiewicz, 1995; cf. Von Braun, 1968). Alas, on December 6, when the American
      rocket began to lift, "it seemed as if the gates of hell had opened up. Brilliant
      stiletto flames shot out from the side of the rocket near the engine. The vehicle
      agonizingly hesitated for a moment, quivered again, and in front of our
      unbelieving, shocked eyes, began to topple" (Halberstam, quoted from
      Heppenheimer, p. 127). Thus, at the UN, "Soviet delegates asked their American
      counterparts if the United States might wish to receive foreign aid under
      Moscow's program of technical assistance to backwards nations" (from
      Heppenheimer, p. 128). Von Braun finally succeeded with the Explorer I on January
      31, 1958, but for the Americans the agonizing wasn't over. On August 21, 1957,
      the Soviet Union launched an intercontinental ballistic missile (ICBM), this time
      carrying a dummy, but able to carry a nuclear bomb (Harford, 1997). So, the first
      ICBMs in the world were aimed at the USA. And then, on the morning of April 12,
      1961, Yuri Gagarin shouted "Poyekhali" ("Let's go!") (quoted from Heppenheimer,
      p. 172), and was launched into space at 9:06 to fly "over America" 51 minutes
      later. Quite naturally, the Soviet authorities wanted to show that Russia had
      been ahead all the time, and historical heroes were in strong demand. The
      Russians didn't have to look far.

PMID- 10900056
TI  - The swing phase of human walking is not a passive movement.
AB  - Many studies have assumed that the swing phase of human walking at preferred
      velocity is largely passive and thus highly analogous to the swing of an unforced
      pendulum. In other words, while swing-phase joint moments are generally nonzero
      during swing, it was assumed that they were either zero or at least negligibly
      small compared to gravity. While neglect of joint moments does not invalidate a
      study by default, it remains that the limitations of such an assumption have not
      been explored thoroughly. This paper makes five arguments that the swing phase
      cannot be passive, using both original data and the literature: (1) Computer
      simulations of the swing phase require muscular control to be accurate. (2) Swing
      phase joint moments, while smaller than those during stance, are still greater
      than those due to gravity. (3) Gravity accounts for a minority of the total
      kinetics of a swing phase. (4) The kinetics due to gravity do not have the
      pattern needed to develop a normal swing phase. (5) There is no correlation
      between pendular swing times and human walking periods in overground walking. The
      conclusion of this paper is that the swing phase must be an actively controlled
      process, and should be assumed to be passive only when a study does not require a
      quantitative result. This conclusion has significant implications for many areas
      of gait research, including clinical study, control theory, and mechanical
      modeling.

PMID- 10900057
TI  - Limb stiffness and postural tremor in the arm.
AB  - The relation between limb stiffness and postural tremor in the upper arm was
      investigated during a pointing task. The task goal was to minimize the amount of
      motion (tremor) at the index finger under levels of increasing limb stiffness.
      This study investigated the influence of increasing limb stiffness on the pattern
      of intra- and interlimb dynamics. The frequency profile of the tremor for all
      limb segments across all conditions displayed two peaks, one between 2-4 Hz and
      another between 8-12 Hz. A third, higher frequency component (20-22 Hz) was
      present in the index finger. Increasing limb stiffness through voluntary co
      contraction of antagonistic muscle pairs effectively constrained the segments of
      the upper limb to increasingly operate as a single biomechanical degree of
      freedom. Higher levels of limb stiffness typically led to an increase in the
      frequency and power of the 2-4 and 8-12 Hz peaks. There was also a decrease in
      the frequency of the 20-22 Hz component of finger tremor. The act of reducing the
      effective degrees of freedom in joint space through voluntarily stiffening of the
      upper limbs also resulted in decreased performance as determined by an increase
      in finger tremor. In the preferred, natural level of limb stiffness, specific
      intralimb segment relations were observed but there was no significant interlimb
      coupling. The intralimb segment correlations were characterized by compensatory
      (out of phase) coupling between the upper arm/forearm and hand/index finger
      segment pairs of each limb that were organized about the action of the wrist
      joint. Increasing the degree of limb stiffness led to a decrease in the level of
      intralimb coupling. The findings suggest that the most efficient mechanism for
      reducing tremor at the periphery is that of compensatory coupling between
      relevant intralimb segments with a low level of limb stiffness.

PMID- 10900058
TI  - Vestibulopathy and the age effects on protective stepping during unperturbed
      standing.
AB  - This study examined the prevalence of protective stepping and accompanying
      preparatory postural responses associated with lateral weight transfer (WT) while
      subjects attempted to sustain stationary standing. The subjects were 92 healthy
      young and older adults and persons with vestibular hypofunction. Force platform
      and whole-body-motion recordings were used to evaluate the prevalence of stepping
      and WT responses during stationary standing (eyes open or closed) using a semi
      tandem foot position. WT components were also evaluated for volitionally
      requested step initiation, and as a function of support base configuration and
      direction of stepping among younger subjects. Only 10% of trials by subjects with
      bilateral vestibular hypofunction (BVH) during semi-tandem standing with eyes
      closed were completed without a step, while 31% of subjects with UVH, 69% of
      healthy elders, and all young healthy subjects were able to stand for the entire
      7-sec trials. WT responses always preceded volitional steps from a standard feet
      parallel orientation but occurred in only 13% of the spontaneous steps. The
      prevalence of WT was influenced by the direction of volitional stepping from semi
      tandem standing, but not by the initial standing width. Spontaneous stepping to
      maintain standing balance is a naturally occurring and prevalent behavior among
      older adults and persons with vestibular hypofunction during tests of quasi
      static standing. Differences between volitional and spontaneous step initiation
      involving the prevalence of preparatory lateral WT are a complex function of
      motor planning, mechanical constraints, and functional context.

PMID- 10900059
TI  - EEG correlates of wrist kinematics as revealed by averaging techniques and Morlet
      wavelet transforms.
AB  - The question regarding the invariant movement properties the central nervous
      system may organize to accomplish different motor task demands as reflected in
      EEG remains unsolved. Surprisingly, no systematic electrocortical research in
      humans has related movement preparation with different movement distance,
      although this area has been widely investigated in the field of motor control.
      This study examined whether the amplitude of discrete wrist movements influences
      the various EEG components both in time and frequency domains. Time-domain
      averaging techniques and Morlet wavelet transforms of EEG single trials were
      applied in order to extract three components [BP(0), N1, and LPS] of movement
      related potentials (MRP) and to quantify changes in oscillatory activity of the
      movement-induced EEG waveforms accompanying 20, 40, and 60 unilateral wrist
      flexion movements. The experimental manipulations induced systematic changes in
      BP(0) and N1 amplitude along the midline (Fz, Cz, and Pz) with 20 movement
      showing the most negativity and 60 the least. The dominant energy within a 30-50
      frequency cluster from bilateral precentral (C3, Cz, C4), frontal (F3, Fz, F4),
      and parietal (P3, Pz, P4) areas with maximum at vertex (Cz) also appeared to be
      sensitive to movement amplitude with the least power observed during 60 wrist
      flexion. This suggests that movement amplitude may be a controllable variable
      that is highly related with task-specific cortical activation primarily at
      frontocentral areas as reflected in EEG.

PMID- 10900060
TI  - Treatment-seeking behavior for acute myocardial infarction symptoms in North
      America and Australia.
AB  - OBJECTIVE: The goal of this study was to compare North American and Australian
      patients' sociodemographic, clinical, cognitive, emotional, and social factors
      associated with behavior in seeking treatment for symptoms of acute myocardial
      infarction. PATIENTS: Subjects included 277 North Americans (mean age, 58 +/- 12
      years; 72% men) and 147 Australians (mean age, 62 +/- 13 years; 66% men) with
      acute myocardial infarction. METHODS: Data were obtained with the Response to
      Symptoms Questionnaire and from the patients' hospital records. RESULTS: In both
      groups, patients who delayed longer (P </=.05) had lower incomes, known diabetes
      mellitus, and symptom onset while at home; in addition, they appraised their
      symptoms as not serious, waited for symptoms to go away, and worried about
      troubling others. Additional factors associated with longer delay in North
      Americans (P </=.05) were older age, intermittent symptoms, and attribution of
      symptoms to a noncardiac cause; other contributing factors include not
      recognizing the symptoms as cardiac and fearing the consequences of seeking help.
      In Australians (P </=. 05), contributing factors were fewer years of education, a
      history of hypertension, and embarrassment about seeking help. CONCLUSION:
      Programs to reduce delay in response to acute myocardial infarction symptoms must
      take account of cognitive and emotional processes and differences in response in
      the particular cultures of patients.

PMID- 10900061
TI  - Therapeutic connection: help seeking on the Internet for persons with implantable
      cardioverter defibrillators.
AB  - PURPOSE: The goal of this study was to understand common themes and shared
      meanings of help seeking on the Internet for persons with implantable
      cardioverter defibrillators (ICDs). SETTING: The study took place over an on
      line, informal, public, electronic bulletin board for persons with ICDs. SAMPLE:
      The sample included 469 postings by 75 users during 15 months. RESULTS: Four
      related themes and 1 constitutive pattern were constructed. Themes included
      seeking and giving meaningful information; sharing personal perspectives;
      storytelling as common grounding; and supportive interacting. The constitutive
      pattern is "therapeutic connection." IMPLICATIONS: Persons with ICDs are
      proactive, using Internet bulletin boards to seek practical information and
      support in coping with daily anxieties of living with an ICD. This form of self
      directed patient education focuses on common experiences of illness versus
      information obtained from health care providers.

PMID- 10900062
TI  - Cardiac tamponade after removal of atrial intracardiac monitoring catheters in a
      pediatric patient: case report.
AB  - The incidence of cardiac tamponade after cardiac surgery is reported as ranging
      from 0.04% to 7%. Although a relatively infrequent complication, tamponade is
      associated with significant morbidity and mortality. Reports of tamponade after
      pediatric cardiac surgery are few and generally associated with postcardiotomy
      syndrome or, less commonly, removal of left atrial or pulmonary artery catheters
      after surgery. A case is presented of cardiac tamponade in a pediatric patient
      resulting from removal of a direct atrial and a pulmonary artery catheter after
      cardiac surgery. The pathophysiology of cardiac tamponade is reviewed and the
      increased risk for pediatric patients is outlined. The case review is conducted
      in the context of existing policies in the reporting institution and
      recommendations for practice are discussed.

PMID- 10900063
TI  - Recognition of patients who require emergency assistance: a descriptive study.
AB  - OBJECTIVE: The purpose of this study was to explore and describe the patient
      characteristics and the process of recognition nurses use to recognize patients
      about whom they are seriously worried. DESIGN: The study design was qualitative,
      exploratory, and descriptive, and it used in-depth interviews and a purposive
      sample. SETTING: The study setting included a teaching hospital and a peripheral
      hospital in a Sydney area health service. PARTICIPANTS: Participants included
      registered nurses (N = 32) with 5 or more years of experience and a history of
      calling the medical emergency team (MET). Mean years of experience as a
      registered nurse was 14 years, and the mean calls to the MET since employed in
      current hospital was 16 calls. FINDINGS: Primary findings showed that nurses
      relied on 4 patient characteristics to apply the MET criterion, "seriously
      worried about a patient." These 4 characteristics were (1) feeling "not right,"
      (2) color, (3) agitation, and (4) observations marginally changed or not changed
      at all. The process used to gather and interpret information to recognize these
      patients who were deteriorating involved touching, observing, listening, feeling
      or sensing, and "knowing." In this process of recognition, nurses relied heavily
      on past experiences and knowledge to detect differences in patient condition.
      CONCLUSIONS: The 4 characteristics need to be included as an explanation for the
      MET criterion, "seriously worried about a patient." Additional validation and
      refinement of the 4 characteristics of the nonspecific MET criterion, "seriously
      worried about a patient," should be carried out. Continuing education programs in
      health care facilities need to support the use of subjective information in
      complex situations that result in decisions to call emergency assistance so
      patients whose conditions are deteriorating can be identified early and responded
      to rapidly.

PMID- 10900064
TI  - A case for multisite studies in critical care.
AB  - Studies in critical care settings are essential to improve critical care
      practice. Critical care research conducted at a single site may be limited with
      respect to sample size leading to large type II error, diminished statistical
      power, decreased generalizability, and inconclusive results. Multiple-site
      studies are more likely to change nursing practice in critical care. They allow
      for larger sample size, broader sampling, faster accrual rates, and meaningful
      subgroup analyses. Successful multisite research requires more thorough planning,
      and deliberate steps are required to ensure its feasibility and acceptability.
      Multisite research protocols can be challenging regarding communication,
      reliability, and data integrity. However, defining and addressing these
      challenges and selecting subjects and settings appropriately can lead to results
      that are more generalizable and relevant to practice.

PMID- 10900065
TI  - Reliability and validity of the Critical Care Family Needs Inventory in a Dutch
      speaking Belgian sample.
AB  - OBJECTIVE: The purpose of the study was to provide psychometric evaluation of the
      Dutch version of the Critical Care Family Needs Inventory. SETTING: The study
      took place in an intensive care unit of a university hospital. PARTICIPANTS: The
      participant group included 200 adult family members visiting a patient within the
      72-hour interval after admission to the intensive care unit. RESULTS: Principal
      factor analysis with varimax rotation resulted in a 5-factor solution
      distinguishing 5 need types: need for information, need for comfort, need for
      support, need for assurance and anxiety reduction, and need for proximity and
      accessibility. The internal consistency of the resulting subscales ranged from
      0.80 to 0.62, and all factors were significantly related to each other. The
      Critical Care Family Needs Inventory subscales were found to be clearly related
      to the demographic variables age, sex, and education level. CONCLUSION: The
      reliability and validity of the Dutch-language Critical Care Family Needs
      Inventory as a diagnostic tool in family needs assessment are supported.

PMID- 10900067
TI  - Adult respiratory distress syndrome complicating Plasmodium falciparum malaria.
AB  - In people who do not have clinical immunity to malaria, infection with the
      malaria parasite could lead to severe complications. We describe a patient who
      had acute and severe lung injury from malaria. A 37-year-old woman had a 24-hour
      history of generalized weakness and chills 2 days after returning from Nigeria.
      She had received mefloquine as prophylaxis, but the patient did not take the
      medication. On admission, a thick blood smear revealed severe Plasmodium
      falciparum parasitemia. She was given doxycycline and quinine, but as her
      parasitemia resolved, dyspnea and hypoxemia developed and she consequently
      required placement of an endotracheal tube. Chest radiography results showed
      bilateral and diffuse infiltrate. This report shows that patients with P
      falciparum malaria should be monitored closely and transferred to an intensive
      care unit for additional management if respiratory distress develops. Physicians
      caring for patients who have recently traveled to malaria-endemic areas need to
      anticipate the possible development of malaria with all of its complications,
      including acute lung injury.

PMID- 10900066
TI  - Effect of the Passy-Muir tracheostomy speaking valve on pulmonary aspiration in
      adults.
AB  - PURPOSE: We determined instances of aspiration in adults with tracheostomies and
      investigated the effect of the Passy-Muir tracheostomy speaking valve on
      occurrences of aspiration. METHODS: Adults with tracheostomies scheduled for
      videofluoroscopic swallowing examinations who met inclusion criteria were
      enrolled. According to study protocol, 6 presentations of thin liquids were
      recorded, 3 with and 3 without the Passy-Muir tracheostomy speaking valve. If a
      cuffed tube was present, the cuff was deflated fully for all presentations.
      RESULTS: Seven of 15 subjects aspirated material on 1 or more presentations of
      thin liquid. Five subjects aspirated material only with the Passy-Muir
      tracheostomy speaking valve off, whereas 2 subjects aspirated material with and
      without the valve. No subject aspirated material while the valve was on
      exclusively. Aspiration was significantly less frequent with the Passy-Muir
      tracheostomy speaking valve on than with it off. CONCLUSIONS: Clinically
      unapparent aspiration occurs commonly in patients with tracheostomies. An
      expiratory occlusive valve can reduce, though not eliminate, occurrences of
      aspiration. CLINICAL IMPLICATION: The benefit of the Passy-Muir tracheostomy
      speaking valve should be evaluated in selected patients who aspirate liquid.

PMID- 10900068
TI  - Differences in skin flora between inpatients and chronically ill outpatients.
AB  - BACKGROUND: Changes in skin flora have been reported among hospitalized and
      critically ill patients, but little is known about whether these changes are
      associated with hospitalization or with chronic, serious illness. The purpose of
      this survey was to compare skin flora of chronically ill outpatients and
      inpatients. METHODS: Aerobic skin flora of forearm and midsternum of 250 patients
      in an intensive care unit and 251 outpatients was sampled by contact plates.
      RESULTS: Mean colony-forming units were 160.6, forearm; 229. 4, sternum (P
      <.000). In logistic regression analysis, patients in the medical intensive care
      unit were significantly more likely to have high counts on the arm (odds ratio,
      2.48; 95% confidence interval: 1.34-4.43; P =.004), and blacks were significantly
      more likely to have higher counts on the sternum when compared with other ethnic
      groups (odds ratio, 1.92; confidence interval: 1.18-3.11; P =. 009). No
      differences were noted between inpatients or outpatients in prevalence of
      methicillin-sensitive Staphylococcus aureus, but inpatients were more likely to
      carry methicillin-resistant Staphylococcus aureus (arm, P =.007; sternum, P
      =.02). Outpatients had a higher prevalence of micrococci and gram-negative
      bacteria at both skin sites (all P <.01) and yeast at the sternal site (P =.007).
      CONCLUSIONS: This comparison provides data to differentiate between effects of
      hospitalization and effects of chronic illness on skin flora.

PMID- 10900069
TI  - Necrotizing fasciitis caused by Aeromonas hydrophila.
AB  - Aeromonas Hydrophila is a gram-negative bacillus commonly found in soil, sewage,
      and fresh or brackish water in many parts of the United States. In healthy
      people, the most common clinical manifestations attributed to Aeromonas are
      diarrhea and soft tissue infections. In people with suppressed immune systems or
      liver disease, A hydrophila can cause meningitis, endocarditis, peritonitis,
      hemolytic-uremic syndrome, or septicemia. We present the first known case of
      fulminant necrotizing fasciitis from A hydrophila that is not associated with
      trauma, liver disease, or immunosuppression.

PMID- 10900070
TI  - p75 neurotrophin receptor signaling: mechanisms for neurotrophic modulation of
      cell stress?
AB  - The recent recognition that the p75 neurotrophin receptor, p75((NTR)), can induce
      apoptotic signals has contributed to the perception that it acts primarily as a
      death receptor. Although the molecular mechanisms of p75(NTR) signaling remain to
      be fully characterized, many of the currently identified pathways activated by
      p75(NTR) may be generally characterized as stress response signals. This review
      describes recent advances in identifying the molecular components involved in
      p75(NTR) signal transduction and suggests that p75(NTR) signaling may more aptly
      serve as a general mechanism for the transduction and modulation of stress
      signals.

PMID- 10900071
TI  - Animal models for inherited peripheral neuropathies: chances to find treatment
      strategies?
AB  - Mutations in four identified genes (peripheral myelin protein 22, P(0), connexin
      32, and the early growth response 2 zinc finger protein) are the cause for
      several forms of inherited peripheral neuropathies that are still incurable
      disorders. Some forms of these disorders are well mimicked by engineered or
      spontaneous rodent mutants that might be instrumental for developing treatment
      strategies. This review focusses on common pathways of pathogenesis of the
      disorders and emphasizes strategies that might be suitable to ameliorate disease
      expression.

PMID- 10900072
TI  - Mature oligodendrocyte apoptosis precedes IGF-1 production and oligodendrocyte
      progenitor accumulation and differentiation during demyelination/remyelination.
AB  - We have documented changes in the oligodendrocyte population during demyelinating
      insult to the adult CNS. Feeding of cuprizone to adult mice led to apoptotic
      death of mature oligodendrocytes followed by profound demyelination of the corpus
      callosum. A regenerative response was initiated even during active demyelination.
      Oligodendrocyte progenitors have begun to proliferate and then accumulate within
      the lesion. Many of these cells may have migrated from the sub-ventricular zone
      and fornix before their accumulation in the demyelinating corpus callosum. The
      accumulation of differentiating oligodendrocyte progenitors was followed closely
      by the reappearance of mature oligodendrocytes and remyelination. Interestingly,
      an increase in IGF-1 mRNA was detected at Week 3 through Week 7, suggesting
      potential involvement in remyelination. Other factors, however, such as PDGF,
      NT3, FGF, jagged, and notch remained unchanged. These results suggest that the
      mature oligodendroglial population depleted by apoptosis is replaced by a newly
      formed oligodendroglial population derived from progenitors; these accumulate and
      seem to differentiate during remyelination.

PMID- 10900073
TI  - NGF ligand alters NGF signaling via p75(NTR) and trkA.
AB  - Nerve growth factor (NGF) binds to two neurotrophin receptors: p75(NTR) and
      p140(Trk) (TrkA). Both receptors dimerize in response to NGF binding. TrkA
      homodimers and heteromers of TrkA and p75(NTR) promote cell survival whereas
      homodimers of p75(NTR) mediate apoptosis upon binding of NGF. The interaction
      between receptor and NGF can be inhibited either on the level of the ligand by
      altering NGF conformation so that NGF is no longer recognized by the receptor or
      on the level of the receptor by blocking the binding site of p75(NTR) or TrkA.
      The effect of altering NGF conformation on NGF signaling was investigated in two
      neuron-like cell lines: in human SK-N-MC cells that express only p75(NTR) and in
      rat PC12 cells that express both p75(NTR) and TrkA. In the present study we
      demonstrate that Ro 08-2750 binds to the NGF dimer thereby probably inducing a
      change in its conformation such that NGF cannot bind to p75(NTR) anymore. In SK-N
      MC cells this leads to inhibition of NGF-induced programmed cell death. In PC12
      cells enhanced signaling through TrkA was observed.

PMID- 10900075
TI  - Transplanted glial cells migrate over a greater distance and remyelinate
      demyelinated lesions more rapidly than endogenous remyelinating cells.
AB  - Glial cell transplantation offers a means of remyelinating areas of demyelination
      in situations where endogenous remyelination fails. How effective such a strategy
      would be if undertaken in human demyelinating disease is not yet clear since it
      is very difficult to create large areas of demyelination in adult rodents that
      would mimic the situation found in a human disease such as multiple sclerosis.
      When CNS tissue is subjected to 40 Grays of X-irradiation, remyelination is
      suppressed in the X-irradiated area unless cells migrate into, or are introduced
      into the X-irradiated area. In the present experiments, by appropriate
      positioning of lead shielding we have created a "starting gate" from which
      oligodendrocyte progenitors must depart in order to colonise areas of
      demyelination. When the starting gate is located at one end of the area of
      demyelination, endogenous cells fail to colonise throughout an area of
      demyelination over the ensuing month. In contrast, when transplanted
      oligodendrocyte precursors are faced with the same situation, the whole area of
      demyelination is remyelinated over the same period. To determine how far
      transplanted cells can migrate to areas of demyelination and also to study how
      quickly the cells can colonise areas of demyelination we injected cells at some
      distance from areas of demyelination made in X-irradiated tissue. In these
      experiments, we found that transplanted cells could repopulate up to 9 mm in 2
      months compared to 4 mm recorded for endogenous cells (Franklin et al. [1997] J.
      Neurosci. Res. 50:337-344). These experiments demonstrate that transplanted cells
      have a far greater ability to colonise areas of demyelination than endogenous
      cells.

PMID- 10900074
TI  - Fibroblast growth factor-9 modulates the expression of myelin related proteins
      and multiple fibroblast growth factor receptors in developing oligodendrocytes.
AB  - The effect of fibroblast growth factor (FGF)-9 on the expression of FGF receptors
      (FGFR) and the major myelin proteins was examined in cultures of developing rat
      brain oligodendrocytes (OLs), using immunological techniques. FGFR-1, -3, and -4
      were expressed at all developmental stages but were not present in isolated
      myelin fractions. By contrast, FGFR-2 protein was predominantly localized to
      differentiating cells and myelin. FGF-9 altered FGFR and myelin protein levels
      during OL differentiation; there was increased expression of FGFR-1 and decreased
      levels of both FGFR-2 and myelin proteins. Further, FGF-9 stimulated mitogen
      associated protein kinase (MAPK) phosphorylation. The effect of FGF-9 on MAPK,
      however, was transient and less robust in progenitor cells than in differentiated
      oligodendrocytes. The effects of FGF-9 and FGF-2 on FGFR and myelin protein
      levels were comparable; both up-regulated FGFR-1, and down-regulated FGFR-2, CNP,
      PLP and MBP. These findings suggest that FGF-9 may be important for glial cell
      development.

PMID- 10900077
TI  - Neural cell response to multiple novel sites on laminin-1.
AB  - The basement membrane protein laminin-1 is a potent stimulator of neurite
      outgrowth for a variety of neuronal cell types. Previous studies have identified
      neurite outgrowth activity in several distinct regions of the laminin-1 molecule.
      In this study, 545 overlapping 12- to 14-mer synthetic peptides, corresponding to
      most of the amino acid sequence of the alpha1, beta1, and gamma1 chains of
      laminin-1, were screened for cell attachment and neurite outgrowth activity using
      primary cultures of mouse cerebellar granule neurons and two neuronal cell lines.
      We identified 48 peptides derived from novel regions of the laminin-1 molecule
      that were positive for neural cell adhesion activity. Only the cerebellar cells
      were found to have true neurite outgrowth activity with certain of the peptides,
      whereas some peptides induced short spike-like process with the cell lines.
      Although 23 of these peptides were active on all 3 cell types screened, 25 others
      showed cell-type specificity in their activity. These studies show that (1) there
      are multiple and distinct sites on laminin-1 for cell adhesion and neurite-like
      outgrowth and (2) that there are neural cell-type-specific active domains. The
      multiple active sites found explains, in part, the potent activity of laminin-1
      on neurite outgrowth.

PMID- 10900076
TI  - Brain-derived neurotrophic factor and trkB are essential for cAMP-mediated
      induction of the serotonergic neuronal phenotype.
AB  - Serotonergic neurons in the central nervous system are crucial in the control of
      autonomic functions and behavior. Mechanisms by which development and maintenance
      of the serotonergic transmitter phenotype is regulated include activation of
      protein kinase A (PKA). Using cultures established from the E14 rat raphe we show
      here that forskolin (10 microM) increases numbers of neurons expressing
      tryptophan hydroxylase (TpOH), the key enzyme of serotonin synthesis, and uptake
      of the false serotonergic transmitter 5, 7-dihydroxytryptamine (5,7-DHT). As
      shown by short-term treatments the effect is due to phenotype induction rather
      than survival. To begin to understand downstream or parallel signaling pathways
      required for the PKA-mediated induction of serotonergic markers, we have studied
      the putative implication of brain-derived neurotrophic factor (BDNF) and its
      receptor trkB. Treatment of raphe neurons with forskolin induced BDNF mRNA
      assayed by competitive RT-PCR. Moreover, trkB-IgG receptor bodies fully prevented
      the forskolin-induced numerical increase in TpOH- and 5,7-DHT-positive cells
      suggesting an implication of a TrkB-activated pathway. TrkC-IgG had no effect.
      K252b, a specific inhibitor of trk kinase activity likewise abolished the
      induction of serotonergic markers by forskolin. In turn, the inductive effect of
      BDNF on serotonergic markers was blocked by KT5720, a specific inhibitor of PKA.
      Taken together, these data suggest that co-activation of cAMP- and trkB-dependent
      signaling pathways plays a crucial role in the regulation of the serotonergic
      neuronal phenotype.

PMID- 10900078
TI  - Intersubunit binding domains within tyrosine hydroxylase and tryptophan
      hydroxylase.
AB  - Tryptophan hydroxylase (TPH), the rate-limiting enzyme in the biosynthesis of the
      neurotransmitter serotonin (5-HT) belongs to the aromatic amino acid hydroxylase
      superfamily, which includes phenylalanine hydroxylase (PAH) and tyrosine
      hydroxylase (TH). The crystal structures for both PAH and TH have been reported,
      but a crystallographic model of TPH remains elusive. For this reason, we have
      utilized the information presented in the TH crystal structure in combination
      with primary sequence alignments to design point mutations in potential
      structural domains of the TPH protein. Mutation of a TH salt bridge (K170E) was
      sufficient to alter enzyme macromolecular assembly. We found that the disruption
      of the cognate intersubunit dimerization salt bridge (K111-E223) in TPH, however,
      did not affect the macromolecular assembly of TPH. Enzyme peaks representing only
      tetramers were observed with size exclusion chromatography. By contrast, a single
      point mutation within the tetramerization domain of TPH (L435A) was sufficient to
      disrupt the normal homotetrameric assembly of TPH. These studies indicate that,
      although the proposed salt bridge dimerization interface of TH is conserved in
      TPH, this hypothetical TPH intersubunit binding domain, K111-E223, is not
      required for the proper macromolecular assembly of the protein. However, leucine
      435 within the tetramerization domain is necessary for the proper macromolecular
      assembly of TPH.

PMID- 10900079
TI  - Participation of syntaxin 1A in membrane trafficking involving neurite elongation
      and membrane expansion.
AB  - Syntaxin 1A has been implicated to play an important role in neurotransmitter
      release by regulating synaptic vesicle fusion. The protein is also suggested to
      be required for other types of membrane fusion such as cellularization during
      embryonic development. In the current study, we overexpressed syntaxin 1A, SNAP
      25b, and VAMP-2 in PC12 cells using recombinant adenoviruses, and determined
      their effects on membrane trafficking involving neurite outgrowth. It was found
      that overexpression of syntaxin 1A inhibited NGF-induced neurite extension, and
      the expressed syntaxin was localized to the plasma membrane, intracellular
      membranes, and the neurite tips. SNAP-25 overexpression slightly enhanced neurite
      elongation, whereas no significant changes in neurite growth was observed in VAMP
      overexpressing cells. The effect of syntaxin 1A in general membrane trafficking
      was further studied by transient transfection of non-neuronal cells. Syntaxin 1A
      expression in HEK 239 and NIH3T3-L1 caused the cells to lose their normal
      morphology, leading to round and smaller cells. Deletion of the C-terminal
      sequence containing the H3 helix and the membrane anchoring domains of syntaxin
      abolished its ability to induce cell morphology changes, whereas removal of the N
      terminal 1-170 amino acid sequence did not affect this activity. These findings
      suggest that in addition to its well documented role in synaptic vesicle fusion,
      syntaxin may function in other non-synaptic membrane trafficking such as neurite
      outgrowth and membrane expansion.

PMID- 10900080
TI  - Immunohistochemical detection of estrogen receptor alpha in male rat spinal cord
      during development.
AB  - The alpha subtype of the estrogen receptor (ERalpha) is present in nociceptive
      and parasympathetic regions of the adult rat spinal cord. The pattern of ERalpha
      expression in the rat spinal cord during development, however, is unknown. We
      used a polyclonal antibody (ER-21) to examine the expression of ERalpha in male
      rat lumbosacral spinal cords at embryonic day (E) 17, E21 (the day before birth),
      postnatal day (P) 1 (the day of birth), P8, P17, P21, and P36. At E17, ERalpha
      immunoreactivity (ERalpha-ir) was observed predominantly in ependymal cells.
      Perinatally, ERalpha-ir was also present in neurons in dorsal root ganglia and in
      fibers capping and within laminae I and II. By P8, ERalpha-ir was absent in
      ependymal cells, but ERalpha-ir fibers were dense in laminae I and II and in
      sympathetic and parasympathetic areas. ERalpha-ir was also present in neurons in
      the dorsal horns. To determine whether ERalpha-ir fibers in laminae I and II were
      processes of spinal neurons or primary afferents, dorsal rhizotomies were
      performed on P17 and P21 animals. Unilateral transection of the lumbosacral
      dorsal roots virtually eliminated ERalpha-ir fibers in the ipsilateral
      superficial laminae, demonstrating that the majority of ERalpha-ir fibers in
      these laminae were primary afferents. We show for the first time that ERalpha-ir
      is present in neurons and fibers of male prenatal and postnatal spinal cord. The
      presence of ERalpha in neuronal nuclei and processes may reflect diverse roles
      and novel mechanisms of action for 17 beta-estradiol in development of spinal
      sensory and autonomic circuitry.

PMID- 10900081
TI  - Regulation of nonphosphorylated and phosphorylated forms of neurofilament
      proteins in the prefrontal cortex of human opioid addicts.
AB  - The neurofilament (NF) proteins (NF-H, NF-M, and NF-L for high, medium, and low
      molecular weights) play a crucial role in the organization of neuronal shape and
      function. In a preliminary study, the abundance of total NF-L was shown to be
      decreased in brains of opioid addicts. Because of the potential relevance of NF
      abnormalities in opioid addiction, we quantitated nonphosphorylated and
      phosphorylated NF in postmortem brains from 12 well-defined opioid abusers who
      had died of an opiate overdose (heroin or methadone). Levels of NF were assessed
      by immunoblotting techniques using phospho-independent and phospho-dependent
      antibodies, and the relative (% changes in immunoreactivity) and absolute
      (changes in ng NF/microg total protein) amounts of NF were calculated. Decreased
      levels of nonphosphorylated NF-H (42-32%), NF-M (14-9%) and NF-L (30-29%) were
      found in the prefrontal cortex of opioid addicts compared with sex, age, and
      postmortem delay-matched controls. In contrast, increased levels of
      phosphorylated NF-H (58-41%) and NF-M (56-28%) were found in the same brains of
      opioid addicts. The ratio of phosphorylated to nonphosphorylated NF-H in opioid
      addicts (3.4) was greater than that in control subjects (1.6). In the same brains
      of opioid addicts, the levels of protein phosphatase of the type 2A were found
      unchanged, which indicated that the hyperphosphorylation of NF-H is not the
      result of a reduced dephosphorylation process. The immunodensities of GFAP (the
      specific glial cytoskeletol protein), alpha-internexin (a neuronal filament
      related to NF-L) and synaptophysin (a synapse-specific protein) were found
      unchanged, suggesting a lack of gross changes in glial reaction, other
      intermediate filaments of the neuronal cytoskeletol, and synaptic density in the
      prefrontal cortex of opioid addicts. These marked reductions in total NF proteins
      and the aberrant hyperphosphorylation of NF-H in brains of opioid addicts may
      play a significant role in the cellular mechanisms of opioid addiction.

PMID- 10900083
TI  - Ontogeny and regeneration in the inner ear

PMID- 10900082
TI  - Manganese concentration in mouse brain after intravenous injection.
AB  - Abnormal deposit of manganese (Mn) in the basal ganglia is often observed in
      patients with chronic liver failure and patients receiving long-term parenteral
      nutrition. Based on the data that (54)Mn is transported into the brain
      efficiently via a transferrin-independent uptake system, Mn concentration in
      mouse brain was determined after intravenous (iv) injection (2 mg Mn/kg/day x 5
      times) of either MnCl(2) or pH 8.6 buffer-treated MnCl(2), which has a higher
      affinity for transferrin than untreated MnCl(2). Brain Mn concentration was
      significantly increased in either case. Brain Mn concentration of MnCl(2) group
      was significantly higher than that of pH 8.6 buffer-treated MnCl(2) groups. Mn
      concentration in the caudate putamen of MnCl(2) group was also significantly
      higher than that of pH 8.6 buffer-treated MnCl(2) group. Ninety seconds after a
      single injection of MnCl(2) (2 mg Mn/kg), brain Mn concentration was remarkably
      increased with blood Mn level, but not 1 hr after injection. On the other hand,
      hepatic Mn concentration was remarkably high 1 hr after injection and the brain
      Mn concentration was increased again at 24 hr, followed by decrease of the
      hepatic Mn concentration. Relative Mn concentrations in the brain 90 sec after
      injection were different from those 24 hr after injection, suggesting that the
      mechanism of the increase of brain Mn concentration via blood Mn level is
      different from that via the redistribution from the liver. Mn ion and/or Mn bound
      to low molecular weight compounds may be involved in abnormal Mn uptake in the
      brain.

PMID- 10900084
TI  - Ventromedial focus of cell death is absent during development of Xenopus and
      zebrafish inner ears.
AB  - We present the normal patterns of programmed cell death in the developing inner
      ears of a primitive anuran, Xenopus laevis, and an ostariophysan fish, Danio
      rerio. A prominent ventromedial focus of cell death was described previously in
      the developing chicken and mouse otocysts. We hypothesize that this focus of cell
      death might be associated with a signaling center that directs morphogenesis of
      the surrounding tissue. Amphibian and fish ear anatomies differ considerably from
      those of birds and mammals, particularly in the structures derived from the
      ventral part (pars inferior) of the otic vesicle. We reasoned that these
      anatomical differences between species might result from a difference in the
      size, location, or presence of a putative morphogenetic signaling center. Using
      in situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end
      labeling (TUNEL) to detect apoptotic cells, we show that developing Xenopus and
      zebrafish ears have apoptotic cells in the eighth cranial ganglia, the developing
      sensory patches, and in various positions in the otocyst wall. However, both
      species lack the persistent ventromedial hot spot of cell death that is
      prominently situated between the pars superior and pars inferior in the chicken
      and mouse otocysts.

PMID- 10900086
TI  - Expression of proneural and neurogenic genes in the embryonic mammalian
      vestibular system.
AB  - One of the most striking aspects of all auditory and vestibular sensory epithelia
      is the mosaic pattern of hair cells and supporting cells. The factors that are
      required for the development of this mosaic have not been determined, however the
      results of recent studies have demonstrated that components of the neurogenic
      (Notch) signaling pathway are expressed in the developing inner ears of a number
      of different vertebrate species. To examine whether this signaling pathway may
      play a similar role in the development of the hair cell mosaic in the mammalian
      vestibular system, the expression patterns of proneural (Math1) and neurogenic
      (Notch1, Jagged2, HES5) genes were examined in the developing mouse inner ear.
      Results indicate that Notch1 is initially expressed throughout the developing
      inner ear and becomes restricted to non-sensory cells within the developing
      sensory epithelia. In contrast, initial expression of Math1 and Jagged2 is
      localized to the developing sensory epithelia and ultimately becomes restricted
      to hair cells. Interestingly, transcripts for HES5, a target of Notch activation,
      are expressed in the developing cristae but not in the saccule or utricle. These
      results are consistent with the hypothesis that formation of the hair cell mosaic
      is regulated through the neurogenic pathway. However the differential expression
      of HES5 within the ear indicates that the downstream targets of Notch1 activation
      are not consistent across all of the sensory epithelia and suggests that the
      effects of activation of Notch1 in the saccule and utricle must be regulated
      through alternate target genes.

PMID- 10900085
TI  - Expression of Pax2 and patterning of the chick inner ear.
AB  - Early regionalized gene expression patterns within the otocyst appear to
      correlate with and contribute to development of mature otic structures. In the
      chick, the transcription factor Pax2 becomes restricted to the dorsal and entire
      medial side of the otocyst by stage 16/17. The dorsal region of the otocyst forms
      the endolymphatic duct and sac (ED/ES), and the cochlear duct is derived from the
      ventromedial region. In the mouse, however, Pax2 expression is reported only in
      the ventromedial and not the dorsal otocyst. In Pax2 null mice, the cochlea is
      missing or truncated, but vestibular structures differentiate normally. Here we
      demonstrate that in the chick, the emerging ED/ES express high levels of Pax2
      even when the position of the emerging ED is altered with respect to its
      environment, either by 180 degrees otocyst rotations about the anterior/posterior
      axis or transplantation of the otocyst into the hindbrain cavity. However, the
      Pax2 expression pattern is plastic in the rest of the otic epithelium after 180
      degrees rotation of the otocyst. Pax2 is upregulated on the medial side (formerly
      lateral), and downregulated on the lateral side (formerly medial and expressing
      Pax2) indicating that Pax2 expression is influenced by the environment. Although
      Pax2 is upregulated in the epithelium after 180 degrees rotations in the region
      that should form the cochlear duct, cochlear ducts are truncated or absent, and
      the ED/ES emerge in a new ventrolateral position. Ablation of the hindbrain at
      the placode or early otic pit stage alters the timing of regionalized Pax2
      expression in the otocyst. The resulting otocysts and ears are generally smaller,
      vestibular structures are abnormal, ED/ES are missing but cochlear ducts are of
      normal length. The hindbrain and dorsal periotic mesenchyme provide unique
      trophic and patterning information to the dorsal otocyst. Our results demonstrate
      that the ED is the earliest structure patterned in the inner ear and that the
      hindbrain is important for its specification. We also show that, although normal
      Pax2 expression is required for cochlear duct development, it is downstream of
      ventral otocyst patterning events.

PMID- 10900087
TI  - Establishment of hair bundle polarity and orientation in the developing
      vestibular system of the mouse.
AB  - The morphological development of the vestibular maculae in the mouse was studied
      in order to identify elements that may determine how hair-bundle polarity is
      established. Utricles and saccules develop in parallel. Hair-bundles first appear
      at embryonic day (E) 13.5. They are initially not polarised and have a kinocilium
      located at the centre of the cell surface surrounded by stereocilia. Polarisation
      is rapidly established as the kinocilium becomes eccentrically positioned. The
      orientation of these polarised bundles is initially not random. It varies
      systematically across the maculae and the general orientation in utricles is the
      opposite of that in saccules. At E15.5, in both maculae, hair-bundle orientation
      angles fall into two populations that differ by approximately 180 degrees
      defining a line of orientation reversal, the position of which varies little
      during subsequent maturation. Many more immature hair bundles appear at E15.5
      suggesting a second wave of hair cell differentiation is initiated. Otoconial
      membrane is produced simultaneously across the entire width of both maculae,
      indicating directional growth of the overlying extracellular matrix is unlikely
      to influence hair-bundle orientation. Growth of both maculae occurs
      asymmetrically, essentially outwards from the striola, but it is most pronounced
      after orientation is defined. Microtubules are prominent in hair cells at the
      earliest stages of their differentiation, but are oriented parallel to the long
      axis of the cell and, thus, may not have a role in directing hair-bundle
      polarity. Microfilament assemblies that are aligned parallel to the apical
      surface and connect to the adherens junctions in supporting cells could provide a
      "framework" for hair-bundle orientation. The striated rootlets of ciliary
      centrioles that are aligned parallel to the cell surface with their tips
      associated with microfilament assemblies at adherens junctions were the only
      structural asymmetry identified that might influence the development of hair
      bundle polarity.

PMID- 10900088
TI  - Hair cells without supporting cells: further studies in the ear of the zebrafish
      mind bomb mutant.
AB  - Each sensory hair cell in the ear is normally surrounded by supporting cells,
      which separate it from the next hair cell. In the mind bomb mutant, as a result
      of a failure of lateral inhibition, cells that would normally become supporting
      cells differentiate as hair cells instead, creating sensory patches that consist
      of hair cells only. This provides a unique opportunity to pinpoint the functions
      for which supporting cells are required in normal hair cell development. We find
      that hair cells in the mutant develop an essentially normal cytoskeleton, with a
      correctly structured hair bundle and well-defined planar polarity, and form
      apical junctional complexes with one another in standard epithelial fashion. They
      fail, however, to form a basal lamina or to adhere properly to the adjacent non
      sensory epithelial cells, which overgrow them. The hair cells are eventually
      expelled from the ear epithelium into the underlying mesenchyme, losing their
      hair bundles in the process. It is not clear whether they undergo apoptosis: many
      cells staining strongly with the TUNEL procedure are seen but do not appear
      apoptotic by other criteria. Supporting cells, therefore, are needed to hold hair
      cells in the otic epithelium and, perhaps, to keep them alive, but are not needed
      for the construction of normal hair bundles or to give the hair bundles a
      predictable polarity. Moreover, supporting cells are not absolutely required as a
      source of materials for otoliths, which, though small and deformed, still develop
      in their absence.

PMID- 10900089
TI  - Hair-cell numbers continue to increase in the utricular macula of the early
      posthatch chick.
AB  - It is generally assumed that hair-cell numbers do not increase in the vestibular
      epithelia of postembryonic birds after hatching. However, for the domestic
      chicken, it is not known when or if hair-cell numbers ever reach a steady state
      level during life. The numbers of hair cells in the utricular maculae of chickens
      from embryonic day (E) 7 to posthatch day (PH) 112 were therefore counted
      directly. Hair-cell numbers increase approximately 15 fold between E7 and PH2,
      from an average of 1,858/macula at E7 to 27,017 at PH2. Between PH2 and PH112
      hair-cell numbers increase by a further 36%, to 36,650/macula. A mathematical
      description of the increase in hair-cell numbers observed with time predicts a
      half life of 29.88 days for a utricular hair cell and a steady-state turnover
      value of 850 hair cells/day by approximately PH60. The patterns of hair and
      supporting cells in the postembryonic utricular macula were also assessed. The
      ratios of supporting cells and hair cells, the average number of supporting cells
      around each hair cell, and the average number of hair cells each supporting cell
      contacts at PH2, PH16 and approximately 2.5 years of age are not significantly
      different. In contrast to the mitotically quiescent basilar papilla where all
      supporting cells contact at least one hair cell, 7.6% of supporting cells in the
      extrastriolar region of the postembryonic utricular macula do not make apical
      contact with a hair cell. These results indicate that hair-cell numbers in the
      utricular macula increase significantly after hatching, and support the concept
      that contact-mediated inhibition influences the proliferative potential of inner
      ear supporting cells.

PMID- 10900090
TI  - Progenitor cell cycling during hair cell regeneration in the vestibular and
      auditory epithelia of the chick.
AB  - We investigated nucleotide-labeling patterns during ongoing hair cell
      regeneration in the avian vestibular epithelium and during drug-induced
      regeneration in the avian auditory epithelium. For utricle experiments, post
      hatch chicks received an injection of bromodeoxyuridine (BrdU) and were allowed
      to survive from 2 hours to 110 days after the injection. Utricles were fixed and
      immunoreacted to detect BrdU. The number of BrdU-labeled nuclei in the hair cell
      and support cell layers of the utricular sensory epithelium changes significantly
      between 2 hours and 110 days post-BrdU. At 2 hours, most labeled cells are
      isolated, while by 5-10 days, the majority of labeled cells are organized in
      pairs that are most frequently composed of a hair cell and a support cell. Pairs
      of labeled cells are seen as late as 110 days. Clusters of more than 3 labeled
      cells are uncommon at all time-points. The total number of labeled cells
      increases approximately 1.5-fold between 5 and 60 days post-BrdU. This increase
      is due primarily to a rise in the number of labeled support cells, and it is
      likely that it represents additional rounds of division by a subset of cells that
      were labeled at the time of the BrdU injection. There is a significant decrease
      in labeled nuclei in the hair cell layer between 60 and 110 days post-BrdU,
      suggesting that hair cells die during this period. To investigate support cell
      recycling in the drug-damaged auditory epithelium, we examined nucleotide double
      labeling after separate injections of BrdU and tritiated thymidine. A small
      number of support cells that incorporate BrdU administered at 3 days post
      gentamicin treatment also label with tritiated thymidine administered between 17
      and 38 hours later. We conclude that a small population of support cells recycles
      during regeneration in both the normal utricle and the drug-damaged basilar
      papilla.

PMID- 10900091
TI  - Growth factor regulation of the cell cycle in developing and mature inner ear
      sensory epithelia.
AB  - Growth factors and other extracellular signals regulate cell division in many
      tissues. Consequently, growth factors may have therapeutic uses to stimulate the
      production of replacement sensory hair cells in damaged human inner ears, thereby
      assisting in alleviating hearing loss and vestibular dysfunction. Assessment of
      the ability of growth factors to stimulate cell proliferation in inner ear
      sensory epithelia is at an early stage. This paper provides a brief account of
      what we know regarding growth factor regulation of cell proliferation in
      developing and mature inner ear sensory epithelia.

PMID- 10900092
TI  - Immune cytokines and dexamethasone influence sensory regeneration in the avian
      vestibular periphery.
AB  - Prior studies have shown that macrophages are recruited to sites of hair cell
      lesions in the avian inner ear in vitro (Warchol, 1997) and in vivo (Bhave et
      al., 1998). Although the avian ear has a high capacity for sensory regeneration
      (Oberholtzer & Corwin, 1997; Stone et al., 1998), the role of macrophages in the
      regenerative process is uncertain. The present study examined the possible
      influence of macrophages and immune cytokines on regenerative proliferation in
      the avian utricle, one of the sensory endorgans of the vestibular system.
      Utricles from post-hatch chicks were placed in organ culture and hair cell
      lesions were created by incubation in neomycin. The cultures were then maintained
      for an additional 24-48 hours in vitro, and some cultures were treated with
      dexamethasone, which inhibits macrophage activation and cytokine production.
      Following fixation, resident macrophages were identified by immunoreactivity to
      CD68. Labeled macrophages were present in all specimens and increased numbers of
      macrophages were observed following neomycin treatment. Regenerative
      proliferation in dexamethasone-treated specimens was reduced by about 50%,
      relative to untreated controls. Additional experiments showed that two macrophage
      secretory products-TGF-alpha and TNF-alpha-enhanced the proliferation of
      utricular supporting cells. The results are consistent with a role for
      macrophages in hair cell regeneration.

PMID- 10900093
TI  - Heregulin enhances regenerative proliferation in postnatal rat utricular sensory
      epithelium after ototoxic damage.
AB  - Hair cell loss due to acoustic and ototoxic damage often leads to hearing and
      balance impairments. Although a spontaneous event in chicks and lower
      vertebrates, hair cell replacement occurs at a much lower frequency in mammals
      presumably due to a very low rate of supporting cell proliferation following
      injury. We report here that heregulin, a member of the neuregulin family,
      dramatically enhances proliferation of supporting cells in postnatal rat
      utricular epithelial sheet cultures after gentamicin treatment, as revealed by
      bromo-deoxyuridine (BrdU) immunocytochemistry. A dose-dependent study shows that
      the maximal effects of heregulin are achieved at 3 nM. The mitogenic effects of
      heregulin are confirmed in utricular whole mount cultures. Autoradiography of the
      utricular whole mount cultures shows that heregulin also enhances the number of
      tritiated thymidine-labeled cells within the hair cell layer. TaqMan quantitative
      RT-PCR analysis and immunocytochemistry reveal that heregulin and its binding
      receptors (ErbB-2, ErbB-3 and ErbB-4) are expressed in the inner ear sensory
      epithelium. Of several ligands activating various ErbB receptors, including
      heregulin, neuregulin-3, beta-cellulin, heparin binding-epidermal growth factor
      (HB-EGF), transforming growth factor-alpha (TGF-alpha) and EGF, heregulin shows
      the most potent mitogenic effects on supporting cells. Because neuregulin-3 that
      signals only through ErbB-4 does not show an effect, these data suggest that
      activation of the ErbB-2-ErbB-3 heterodimeric complexes, rather than ErbB-4, is
      critical for the proliferative response in the utricular sensory epithelium. In
      addition, gentamicin treatment induces an upregulation of heregulin mRNA.
      Considered together, heregulin may play an important role in hair cell
      regeneration following ototoxic damage.

PMID- 10900094
TI  - Regulation of p27Kip1 during gentamicin mediated hair cell death.
AB  - The INK4 and Kip/Cip families of Cyclin Dependent Kinase inhibitors (CKIs) are
      regulators of the cell cycle. In addition, CKIS including p27(Kip1) can protect
      cells from apoptosis in vitro. However, little is known about protective effect
      of p27(Kip1) in vivo. We used systemic treatment with aminoglycosides to induce
      hair-cell death in the basilar papilla (BP), the auditory organ of the avian
      inner ear, and characterised the expression of p27(Kip1) with confocal and
      immunofluorescence microscopy. In contrast to the adult mammalian cochlea where
      p27(Kip1) is expressed only in supporting cells, p27(Kip1) is found in the nuclei
      of both hair cells and supporting cells in the BP of the normal, mature bird.
      Forty-eight hours after gentamicin treatment, hair cells with TUNEL positive
      nuclei and hair cells with pyknotic nuclei were both detected, suggesting many
      hair cells die by apoptosis. When the BP was double labelled for p27(Kip1) and
      myosin VIIa, a hair-cell specific protein, all dying hair cells that had been
      ejected from the epithelium were found to be myosin VIIa positive but negative
      for p27(Kip1) even though nuclear remnants were still visible. In the transition
      zone where partial hair-cell loss occurs, freshly ejected hair cells lying
      immediately above the surface of the BP no longer expressed p27(Kip1). Damaged
      hair cells within the epithelium in the transition zone contained p27(Kip1) in
      their cytoplasm but not in their nuclei. These data support recent in vitro
      findings suggesting that p27(Kip1) protects cells from apoptosis and that its
      downregulation may be a general feature of programmed cell death.

PMID- 10900095
TI  - Morphological and molecular changes in the inner hair cell region of the rat
      cochlea after amikacin treatment.
AB  - This study investigates the morphological and molecular changes that occur in the
      inner hair cell area of the rat cochlea following aminoglycoside treatment. Rats
      were injected daily with 500 mg/kg of amikacin between postnatal day 9 (PND9) and
      PND16. Cochleae were examined at PND16 to PND120 using both scanning and
      transmission electron microscopy and molecular fluorescent labeling. The inner
      hair cells showed obvious signs of apoptosis in response to amikacin treatment
      and most of them were missing by one week after the end of the aminoglycoside
      exposure period. Concomitantly, the epithelium became scarred as the surrounding
      supporting cells expanded and filled the space vacated by the missing IHCs. The
      mid-basolateral region of these modified supporting cells was surrounded by many
      afferent and efferent terminals. However, these cells expressed neither calbindin
      nor SNAP25, proteins that are both expressed by IHCs in the normal, untreated
      organ of Corti in the rat. In addition, these supporting cells remained attached
      to the basal lamina by a thin cytoplasmic process. The supporting cells
      surrounding the inner hair cells therefore appear unable to convert directly into
      inner hair cells following aminoglycoside induced hair-cell loss but may be able
      to provide trophic support for the remaining afferent and efferent neurites.

PMID- 10900096
TI  - Apoptosis of inner hair cells caused by laser ablation of their spiral ganglion
      neurons in cultures of the mouse organ of Corti.
AB  - Laser beam ablation of spiral ganglion neurons was performed in seven organotypic
      cultures of the newborn mouse cochlea between 5 and 8 days in vitro, with a
      recovery period of from 18 hours to 3 days. Direct somatic injury (laser or
      mechanical) inflicted on hair cells does not necessarily cause their death; many
      of them survive, repair damage and re-establish their neurosensory connections.
      By contrast, laser irradiation and ablation of their afferent spiral ganglion
      neurons causes a most spectacular degeneration of sensory cells within 18-48
      hours after the insult. Ultrastructurally, the degenerated hair cells
      characteristically the inner hair cells-display "dark-cell vacuolar degeneration"
      that combines the signs of apoptotic death (the peripheral condensation of
      nuclear chromatin and nuclear pyknosis) with signs of cell edema, vacuolization
      and necrosis. The ultimate condensation of the cytoplasm gives the dead cells a
      jet black appearance. The irradiated spiral ganglion neurons die displaying
      similar pathological characteristics. The extent and locus of inner hair cell
      degeneration correspond to that of ablated spiral ganglion neurons: ultimately
      the ablation of one neuron causes degeneration of a single inner hair cell within
      the closest radial segment of the afferent innervation. The elimination of spiral
      ganglion neurons by mechanical means does not affect hair cell survival. It is
      inferred that the laser pulse acts as a stimulus depolarizing the neuronal
      membrane of the spiral ganglion neurons and their radial fibers and causing the
      excitotoxic death of their synaptic sensory cells through excessive stimulation
      of the glutamatergic receptors. Reciprocal pre-and postsynaptic synapses between
      the afferent dendrites and inner hair cells in culture could possibly serve as
      entryways of the stimulus. The pathogenesis of this apparent transsynaptically
      induced apoptotic death of inner hair cells will be further examined in culture.

PMID- 10900097
TI  - A temporospatial map of adhesive molecules in the organ of Corti of the mouse
      cochlea.
AB  - In the nervous system, several classes of cell-surface and extracellular matrix
      molecules have been implicated in processes such as neural growth, fasciculation,
      pathfinding, target recognition and synaptogenesis, which require cell-to-cell or
      cell-to-substrate binding. In the developing mouse cochlea, little is known about
      the types of cell-surface and extracellular matrix molecules existing along the
      neural growth paths or their possible roles in development. Whole mount and
      sectioned cochlear tissue were immunolabeled for six different adhesive molecules
      - neural cell adhesion molecule (NCAM), polysialic acid (PSA), neural cell
      adhesion molecule L1, E-cadherin, syndecan-1 and tenascin-C. A temporospatial map
      of adhesive molecule distribution in the basal turns of the mouse cochlea was
      generated. Distributions of adhesive molecules were compared to each other and to
      the known progress of neural development in the region. This comparison
      demonstrated differences in the complements of adhesive molecules between the
      inner and outer hair cell regions, and variations in the expressions of adhesion
      molecules among different types of nerve fibers. In addition, developmental
      changes in the adhesive environment around and beneath the outer hair cells
      coincided with the known timing of the appearance of morphologically defined
      efferent synapses. These observations raise the possibility that molecular
      differences at the cell surface of inner and outer hair cells are one way that
      ingrowing neurites distinguish different environments to determine their growth
      routes and synaptic partners in the cochlea. In addition these observations
      demonstrate the potential for differential signaling of afferent and efferent
      innervation by altering the microenvironments in which synapses are formed.

PMID- 10900098
TI  - Tailchaser (Tlc): a new mouse mutation affecting hair bundle differentiation and
      hair cell survival.
AB  - We have undertaken a phenotypic approach in the mouse to identifying molecules
      involved in inner ear function by N-ethyl-N-nitrosourea mutagenesis followed by
      screening for new dominant mutations affecting hearing or balance. The pathology
      and genetic mapping of the first of these new mutants, tailchaser (Tlc), is
      described here. Tlc/+ mutants display classic behavioural symptoms of a
      vestibular dysfunction, including head-shaking and circling. Behavioural testing
      of ageing mice revealed a gradual deterioration of both hearing and balance
      function, indicating that the pathology caused by the Tlc mutation is
      progressive, similar to many dominant nonsyndromic deafnesses in humans. Based on
      scanning electron microscopy (SEM) studies, Tlc clearly plays a developmental
      role in the hair cells of the cochlea since the stereocilia bundles fail to form
      the characteristic V-shape pattern around the time of birth. By young adult
      stages, Tlc/+ outer hair bundles are grossly disorganised although inner hair
      bundles appear relatively normal by SEM. Increased compound action potential
      thresholds revealed that the Tlc/+ cochlear hair cells were not functioning
      normally in young adults. Similar to inner hair cells, the hair bundles of the
      vestibular hair cells also do not appear grossly disordered. However, all types
      of hair cells in the Tlc/+ inner ear eventually degenerate, apparently regardless
      of the degree of organisation of their hair bundles. We have mapped the Tlc
      mutation to a 12 cM region of chromosome 2, between D2Mit164 and D2Mit423. Based
      on the mode of inheritance and map location, Tlc appears to be a novel mouse
      mutation affecting both hair cell survival and stereocilia bundle development.

PMID- 10900099
TI  - Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary
      acquired melanosis with atypia: clinical experience with histopathologic
      observations.
AB  - OBJECTIVES: To clinically evaluate topical mitomycin chemotherapy in patients
      with diffuse, multifocal, or recurrent primary acquired melanosis with atypia
      and/or conjunctival malignant melanoma and to histopathologically study ocular
      tissue samples obtained before and after treatment. METHODS: Chemotherapy with
      topical mitomycin, 0.04% 4 times daily, was administered for 28 days as the
      primary and only treatment in 7 patients (after biopsy) and for 7 days as
      adjuvant therapy to excision and cryotherapy in 5 patients. Mean follow-up was 38
      months. Five patients developed subconjunctival recurrences, for which 2
      underwent orbital exenteration and 3 were treated conservatively. Histopathologic
      specimens of conjunctival, adnexal, and ocular tissues obtained before and after
      chemotherapy were evaluated. RESULTS: Regression of tumor was observed in 11
      patients with primary or adjuvant topical mitomycin chemotherapy. One patient
      with nodular melanoma was resistant to mitomycin chemotherapy. Histopathologic
      findings included regionally variable conjunctival epithelial atrophy and
      thinning. Dyskeratosis and focal keratinization in conjunctival epithelium were
      noted. Epithelial nuclei were occasionally pyknotic in areas of atrophic
      epithelium. Subepithelial inflammation was present and was most intense in areas
      with severe atrophy and/or keratosis. Two patients with primary treatment and 2
      with adjuvant treatment developed subconjunctival recurrence. In patients with
      recurrent malignant melanoma, the deeper layers of the lamina propria were
      involved, with sparing of the epithelium and superficial lamina propria.
      Transient keratoconjunctivitis was observed in all patients during treatment. In
      evaluation of the exenteration specimens, corneal, scleral, episcleral, retinal,
      and anterior structures were within normal limits. CONCLUSIONS: Topical mitomycin
      chemotherapy was found to induce regression of conjunctival melanoma and primary
      acquired melanosis with atypia. When mitomycin chemotherapy was used as an
      adjuvant to excision and cryotherapy, 2 (40%) of 5 patients experienced tumor
      recurrence at a mean of 4.3 years' follow-up. Our histopathologic findings
      demonstrated a long-term mitomycin chemotherapy-related effect on the
      conjunctiva. The degree of chronic atrophy and inflammation was not clinically
      significant. The pattern of effect and location of recurrent disease suggest that
      this regimen of topical mitomycin chemotherapy was most effective for superficial
      tumors. No complications that would preclude use of our dose regimen were noted.
      Although subconjunctival or orbital recurrences were noted, topical mitomycin
      chemotherapy warrants further investigation as an alternative treatment for
      primary acquired melanosis with atypia and conjunctival malignant melanoma. Arch
      Ophthalmol. 2000;118:885-891

PMID- 10900100
TI  - Bilateral anterior lenticonus: Scheimpflug imaging system documentation and
      ultrastructural confirmation of Alport syndrome in the lens capsule.
AB  - BACKGROUND: Alport syndrome is a combination of proteinuria, hematuria, and
      neurosensory high-frequency deafness. Bilateral anterior lenticonus may be a late
      sign. Diagnosis relies on characteristic electron microscopy changes of
      glomerular basement membranes in renal biopsy specimens. PATIENT: A 38-year-old
      man was seen for progressive visual acuity loss (20/400 OU; best-corrected visual
      acuity, 20/60 OD and 20/50 OS). Findings from slitlamp examination included
      bilateral anterior lenticonus and central posterior subcapsular cataract,
      documented using a modified Scheimpflug imaging system. Retinal pathology was not
      present. On detailed questioning, a history of microhematuria and proteinuria
      since childhood and progressive high-frequency deafness for years were
      discovered. The family history was negative for nephropathies, deafness, or eye
      diseases. Cataract extraction rehabilitated the patient's vision. RESULTS:
      Electron microscopy of a fragile capsulorhexis specimen showed typical thinned
      basal lamina with basement membrane disruptions. CONCLUSIONS: Anterior lenticonus
      is a rare bilateral progressive developmental anomaly. More than 90% of cases are
      associated with Alport syndrome. For diagnosis of Alport syndrome, the presence
      of 3 of 4 criteria is required: family history positive for Alport syndrome,
      progressive intra-auricular deafness, characteristic eye anomalies, and positive
      findings from glomerular ultrastructural examination. We believe that
      ultrastructural proof of anterior lenticonus may also be provided in the lens
      capsule. Arch Ophthalmol. 2000;118:895-897

PMID- 10900101
TI  - Accuracy and implications of a reported family history of glaucoma: experience
      from the Glaucoma Inheritance Study in Tasmania.
AB  - OBJECTIVES: To ascertain the prevalence of previously undiagnosed primary open
      angle glaucoma (POAG) within 5 large POAG pedigrees and to evaluate the
      reliability of a reported family history of glaucoma within these pedigrees.
      METHODS: The Glaucoma Inheritance Study in Tasmania (GIST) identified several
      large adult POAG pedigrees. Intraocular pressure (IOP), optic disc
      stereophotography, and automated perimetry were performed on all adult pedigree
      members. Participants were classified as normal (IOP <22 mm Hg and normal optic
      disc and field); glaucoma suspect (normal field, but an IOP >/=22 mm Hg and/or
      suspicious optic disc); or POAG (field defect and glaucomatous optic disc). Some
      individuals with POAG had been previously diagnosed by their local
      ophthalmologist; others were diagnosed as a result of the GIST project. Family
      members with a prior diagnosis of POAG were asked to report if they were aware of
      any relatives with POAG. This reported family history was then directly compared
      with the actual pedigree (before the diagnosis of new cases) to calculate
      agreement. MAIN OUTCOME MEASURE: The rate of glaucoma in pedigrees and percentage
      of previously diagnosed glaucoma cases who were aware of the positive family
      history of POAG. RESULTS: Four hundred forty-two subjects (mean age, 54 years
      [range, 13-97 years]) from 5 pedigrees were examined: 316 subjects (71%) were
      normal, 47 (11%) were previously diagnosed with POAG, and 8 (2%) were previously
      diagnosed glaucoma suspects; 30 cases (7%) of POAG and 41 suspects (9%) were
      newly diagnosed as a direct result of the GIST examination. Of the 47 previously
      diagnosed POAG cases, 41 were questioned about their prior knowledge of any
      family history and 11 (27%) were unaware of their family history of POAG.
      CONCLUSIONS: Examination of all adult subjects from POAG families yields new
      cases. Even in large POAG pedigrees, 27% of previously diagnosed POAG patients
      were unaware of their positive family history. These findings suggest that a
      higher percentage of adult POAG may be inherited than hitherto reported. Arch
      Ophthalmol. 2000;118:900-904

PMID- 10900102
TI  - Combined pars plana vitrectomy and sutured posterior chamber implant.
AB  - OBJECTIVE: To describe the surgical technique, visual acuity results, and
      complications of sutured posterior chamber intraocular lenses with complete pars
      plana vitrectomy. METHOD: A retrospective review of 63 eyes was combined with a
      telephone survey of the patients and their ophthalmologists. RESULTS: The
      preoperative diagnoses were trauma, 25 eyes; ectopia lentis, 24 eyes; aphakia
      following retinal detachment surgery, 7 eyes; cataract surgery, 6 eyes; and
      endophthalmitis, 1 eye. Mean follow-up was 20 months. Preoperative best-corrected
      visual acuity was 20/40 or better in 36% (23 of 63 eyes), 20/60 to 20/120 in 33%
      (21 of 63 eyes), and 20/200 or worse in 31% (19 of 63 eyes) improving to 20/40 or
      better in 76% (48 of 63 eyes), 20/60 to 20/120 in 18% (11 of 63 eyes), and 20/200
      or worse in 6% (4 of 63 eyes) at final follow-up. Preoperative complications
      included iatrogenic retinal breaks in 3 cases, difficulty with a fixation suture
      in 1 case, and mild vitreous hemorrhage in 1 case. Postoperative complications
      included retinal detachment in 2 cases, choroidal hemorrhage in 1 case,
      intermittent pupil capture in 9 cases, self-limiting vitreous hemorrhage in 3
      cases, and late intraocular lenses dislocation in 1 case. CONCLUSIONS: Suturing a
      posterior chamber implant concurrently, or following, a complete pars plana
      vitrectomy is a safe procedure. Complete vitrectomy may reduce the rate of long
      term complications. Optimal visual rehabilitation can be achieved without the
      need for contact lens wear with an acceptable additional risk of surgical
      complications. Arch Ophthalmol. 2000;118:905-910

PMID- 10900103
TI  - Retinopathy progression and visual outcomes after phacoemulsification in patients
      with diabetes mellitus.
AB  - OBJECTIVES: To determine the rate of progression of diabetic retinopathy after
      phacoemulsification surgery, and whether surgeon experience and/or surgical
      duration adversely affect visual outcome. METHODS: A retrospective review of 150
      eyes of 119 diabetic patients who underwent phacoemulsification surgery during a
      5-year period was performed. Data collected included patient age, sex, type and
      duration of diabetes, diabetic control, associated systemic health factors,
      preoperative visual acuity and retinopathy grade, duration of surgery,
      intraoperative complications, and postoperative course. The effect of these
      factors on visual outcome and rate of retinopathy progression was studied by
      means of univariate and stepwise multivariate logistic regression analyses.
      Resident and private cases were compared. RESULTS: Visual acuity improved by 2 or
      more lines in 117 eyes (78%); 93 eyes (62%) had a final visual acuity of at least
      20/40. Retinopathy progression was seen in 37 eyes (25%) with 6 to 10 months of
      follow-up. Preoperative nonproliferative diabetic retinopathy, proliferative
      diabetic retinopathy, and limited surgical experience were statistically
      associated with retinopathy progression and poor visual outcome. CONCLUSIONS: The
      visual results and rate of retinopathy progression after phacoemulsification
      surgery in our series did not differ significantly from those reported that used
      other techniques. Nonproliferative and proliferative diabetic retinopathy and
      surgical inexperience resulted in an increased rate of retinopathy progression.
      Arch Ophthalmol. 2000;118:912-917

PMID- 10900104
TI  - Uveal melanoma in young patients.
AB  - OBJECTIVE: To study the clinical profile of young patients with uveal melanoma.
      DESIGN: Retrospective case-control series. SETTING: Tertiary referral center.
      PATIENTS: Data on 63 patients aged 20 years or younger with uveal melanoma were
      reviewed for clinical profile and association with oculo(dermal) melanocytosis,
      familial uveal melanoma, dysplastic nevus syndrome, cutaneous melanoma, and other
      second malignant neoplasms. RESULTS: Of 8000 patients with uveal melanoma, 63
      (0.8%) were found in patients who were 20 years of age or younger. The median age
      at diagnosis was 16 years, and the youngest patient was 3 years old. Sixty-two
      patients (98%) were white, and uveal melanoma was unilateral in all cases. Seven
      patients (11%) had oculo(dermal) melanocytosis. Two patients (3%) had dysplastic
      nevi syndrome, and personal history of cutaneous melanoma was observed in 1
      patient (2%). No other second cancers were present in any patient. The 5- and 15
      year posttreatment survival estimates were 0.95 (95% confidence interval, 0.87
      1.00) and 0.77 (95% confidence interval, 0.52-1.00), respectively. CONCLUSIONS:
      Uveal melanoma is rare in children or teenagers. It occurs in a heterogeneous
      group displaying various associations, especially with oculo(dermal)
      melanocytosis. Oculo(dermal) melanocytosis is 9 times (95% confidence interval,
      3.6-22.8) more common in young patients with uveal melanoma than in the general
      population with uveal melanoma. Young patients with uveal melanoma have short
      term (5-year) survival better than that of adults, but the long-term (15-year)
      survival is similar to that of adults. Arch Ophthalmol. 2000;118:918-923

PMID- 10900105
TI  - Clinical-histopathological correlation of the abnormal retinal vessels in
      cerebral malaria.
AB  - BACKGROUND: Clinically abnormal retinal vessels unique to cerebral malaria have
      previously been shown to be associated with a poor outcome in African children.
      There have been no studies of the histopathological correlates of these vessels.
      DESIGN: This is a descriptive study of the clinical-histopathological correlates
      of the retinal vessels of 11 children who died with cerebral malaria. RESULTS:
      The retinal vessels in children with cerebral malaria contained many parasitized
      red blood cells; these cells tended to cluster at the periphery of vessels or, in
      the case of capillaries, to fill the vessel. Those with late-stage parasites had
      markedly reduced amounts of hemoglobin. The pattern of dehemoglobinization
      corresponds to the pattern of clinically abnormal vessels. CONCLUSIONS: The
      sequestration of late-stage parasitized red blood cells with reduced amounts of
      hemoglobin accounts for the unique white and pale orange retinal vessels seen in
      cerebral malaria. Clinical examination of these "marked" vessels offers a method
      to monitor a basic pathophysiological process of cerebral malaria in vivo. Arch
      Ophthalmol. 2000;118:924-928

PMID- 10900106
TI  - Relentless placoid chorioretinitis: A new entity or an unusual variant of
      serpiginous chorioretinitis?
AB  - OBJECTIVE: To characterize an unusual clinical entity resembling acute posterior
      multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis
      but with an atypical clinical course. PATIENTS: We describe 6 patients, aged 17
      through 51 years, exhibiting this unusual entity who were seen at 6 different
      centers from 1984 to 1997. RESULTS: The acute retinal lesions in this series were
      similar to those of APMPPE or serpiginous choroiditis, both clinically and on
      fluorescein and indocyanine green angiography. However, the clinical course,
      number of lesions, and location of these lesions were atypical. These patients
      had evidence of numerous posterior and peripheral retinal lesions predating or
      occurring simultaneously with macular involvement. Older, healing pigmented
      lesions were often accompanied by the appearance of new active white placoid
      lesions. Additionally, these cases all demonstrated prolonged periods of activity
      resulting in the appearance of more than 50 and sometimes hundreds of lesions
      scattered throughout the fundus. Growth of subacute lesions and the appearance of
      new lesions continued for 5 to 24 months after initial examination, and relapses
      were common. CONCLUSIONS: This entity has clinical features similar to APMPPE and
      serpiginous choroiditis but has a prolonged progressive clinical course and
      widespread distribution of lesions. It may represent a variant of serpiginous
      choroiditis or may be a new entity. We call it relentless placoid
      chorioretinitis. Arch Ophthalmol. 2000;118:931-938

PMID- 10900107
TI  - Endophthalmitis after pediatric strabismus surgery.
AB  - OBJECTIVE: To report 6 cases of endophthalmitis after pediatric strabismus
      surgery. METHODS: Retrospective review of initial signs, clinical findings,
      treatment, culture results, and visual and anatomical outcomes in 6 eyes of 6
      children treated at 2 tertiary care institutions between 1983 and 1998. RESULTS:
      Four boys and 2 girls aged 8 months to 6 years (median age, 2 years) developed
      lethargy and asymmetric eye redness, with or without eyelid swelling or fever,
      within 4 days of surgery. At diagnosis (median, postoperative day 6) clinical
      findings included periorbital swelling, redness and leukocoria due to vitritis,
      and, in some cases, hypopyon. Treatment included pars plana vitrectomy and
      intravitreal and systemic antibiotics in all cases. Vitreous cultures grew
      Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus.
      Within 6 months of strabismus surgery, visual acuity was no light perception in
      all eyes and 3 eyes had been enucleated. The 3 remaining eyes were prephthisical.
      CONCLUSIONS: Endophthalmitis after pediatric strabismus surgery is rare. Children
      may not recognize or verbalize symptoms. Causative organisms are virulent. Visual
      and anatomical outcomes are poor. Lethargy, asymmetric eye redness, eyelid
      swelling, or fever in the postoperative period, even if initial postoperative
      examination results are normal, should prompt urgent ocular examination. The
      diagnosis of endophthalmitis may be made when biomicroscopic or indirect
      ophthalmoscopic examination confirms the presence of vitreous opacification with
      or without hypopyon. Arch Ophthalmol. 2000;118:939-944

PMID- 10900108
TI  - The usefulness of the cervical range of motion device in the ocular motility
      examination.
AB  - OBJECTIVES: To determine if the cervical range of motion (CROM) device, an
      instrument designed to assess the range of motion in the cervical spine, may be
      suited for accurately quantifying the magnitude of a patient's abnormal head
      posture, limitation of ductions, or range of single binocular vision at distance
      fixation. METHODS: The CROM device was used to measure abnormal head postures in
      10 subjects and limitations of ductions in 12 patients by 2 masked observers. In
      addition, it was used to test the diplopia field in 17 patients at one third of a
      meter and 6 m. These findings were compared with a standard diplopia field
      performed on a Goldmann perimeter. RESULTS: For 10 subjects with abnormal head
      postures, the findings of the 2 observers had a mean+/-SD difference of 1.0
      degrees +/-0.7 degrees (P=.15, paired t test). For the assessment of limitations
      of ductions, the findings of the 2 observers had a mean+/-SD difference of 1.1
      degrees +/-2.6 degrees (P=.17, paired t test). For the 17 patients undergoing
      diplopia field testing, the results obtained on the Goldmann perimeter and with
      CROM device at the same test distance were essentially identical (mean+/-SD
      difference of 1.3 degrees +/-0.95 degrees; P=.88, paired t test); however, there
      was a significant difference between the results at one third of a meter and 6 m
      (mean+/-SD difference of 6.0 degrees +/-1.1 degrees for esotropic patients
      [P=.001]; mean+/-SD difference of 6.0 degrees +/-2.6 degrees for exotropic
      patients [P=.002]). CONCLUSION: The CROM device seems to be suitable for testing
      abnormal head postures, limitations of ductions, and the range of single
      binocular vision. Arch Ophthalmol. 2000;118:946-950

PMID- 10900109
TI  - Ocular effects of apraclonidine in Horner syndrome.
AB  - OBJECTIVE: To determine the location of action of apraclonidine, an alpha
      adrenergic receptor agonist that reduces aqueous production and lowers
      intraocular pressure (IOP). METHODS: The study cohort consisted of 6 patients
      with Horner syndrome (decreased or absent sympathetic innervation of 1 eye). We
      instilled 1% apraclonidine into the affected eye, and the changes in IOP and
      pupil diameter (PD) of both eyes were measured over 4 hours. In a separate
      session, apraclonidine was instilled into the normal eye and the measurements
      were repeated. RESULTS: The average baseline IOP was 16.3 mm Hg for affected eyes
      and 16.7 mm Hg for normal eyes. The average maximum ipsilateral reduction in IOP
      was 5.8 mm Hg in affected eyes and 5.2 mm Hg in normal eyes; this difference was
      not statistically significant. The average baseline PDs for affected and normal
      eyes were 3.2 mm and 4.2 mm, respectively. Instillation of apraclonidine into
      affected eyes produced mydriasis of 1.0 to 4.5 mm; baseline anisocoria reversed
      in all patients. There was no significant change in the PD of normal eyes after
      ipsilateral instillation of apraclonidine. CONCLUSIONS: Apraclonidine's major
      site of pharmacologic action for reduction of aqueous production is on
      postjunctional alpha(2) receptors in the ciliary body. The up-regulation of alpha
      receptors that occurs with sympathetic denervation unmasks apraclonidine's
      alpha(1) effect, which clinically causes pupil dilation. Apraclonidine may be a
      useful medication for the diagnosis of Horner syndrome. Arch Ophthalmol.
      2000;118:951-954

PMID- 10900110
TI  - H-7 effects on the structure and fluid conductance of monkey trabecular meshwork.
AB  - OBJECTIVE: To determine the effects of H-7 (1-[5-isoquinoline sulfonyl]-2-methyl
      piperazine) on the structure and fluid conductance of the trabecular meshwork of
      live cynomolgus monkeys. METHODS: Fluid outflow was measured by constant pressure
      perfusion of the anterior chamber with cationized and noncationized gold solution
      with or without H-7 in opposite eyes. The eyes were fixed by infusing Ito
      solution and enucleated. Anterior segments were cut into 4 sections, fixed in
      immersion solution, and embedded in epoxy resin-812. Trabecular meshwork
      morphologic features were studied by light and electron microscopy. RESULTS: H-7
      affected trabecular meshwork organization and increased fluid outflow. H-7
      expanded the intercellular spaces in the juxtacanalicular meshwork, accompanied
      by removal of extracellular material. The inner wall cells of the Schlemm canal
      became highly extended, yet cell-cell junctions were maintained. Colloidal gold
      particles were detected only in limited areas along the subcanalicular region in
      control eyes; after H-7 treatment, gold was widely seen along the entire inner
      canal wall. Most inner wall cells in H-7-treated eyes, but only few cells in
      control eyes, contained gold-loaded vesicles. CONCLUSION: H-7 inhibits cell
      contractility, leading to "relaxation" of the trabecular outflow pathway,
      expanding the draining surface, and permitting more extensive flow through the
      meshwork. CLINICAL RELEVANCE: By inhibiting cellular contractility and relaxing
      the trabecular meshwork, the protein kinase inhibitor H-7 increases outflow
      facility and reduces intraocular pressure and thus has potential as an ocular
      hypotensive antiglaucoma medication. Arch Ophthalmol. 2000;118:955-962

PMID- 10900111
TI  - Effect of scleral shortening on axial length.
AB  - BACKGROUND: Partial thickness sclerectomy is the most commonly employed scleral
      shortening technique used in conjunction with pars plana vitrectomy in the repair
      of myopia-associated macular holes in patients with staphyloma. Recently, scleral
      shortening induced through scleral invagination has been advocated as an adjunct
      in retinal translocation surgery. OBJECTIVE: To determine whether a correlation
      exists between the amount of sclera infolding and the posttreatment reduction in
      axial length (AL) as a result of lamellar scleral resectioning or full-thickness
      scleral invagination. METHODS: Three groups of 10 eyes each underwent lamellar
      scleral resection with dissection of 6, 8, and 10 mm in height, and 1 group of 10
      eyes underwent a 10-mm invagination. Presurgical and postsurgical external AL of
      globes with stabilized intraocular pressure was measured to +/-0.022-mm
      precision. RESULTS: Average (+/-SD) AL shortening following lamellar resections
      for 6-, 8-, and 10-mm groups were 1.50+/-0.24, 2.10+/-0.13, and 2.65+/-0.24 mm,
      respectively, and 2.50+/-0.23 mm for the 10-mm invagination group. Differences in
      AL before and after scleral shortening were found to be significantly different
      between dissections of different heights (P<.05), and not significantly different
      between the 10-mm resection and invagination groups (P>.17). The AL of each group
      was shortened by approximately 25% of the resection-invagination height. The
      relation was quasilinear. CONCLUSIONS: Lamellar scleral resection and nonresected
      scleral invagination reduce the ocular AL. The extent of the reduction
      significantly correlates to the amount of removed or invaginated sclera. CLINICAL
      RELEVANCE: Surgical shortening of the sclera is useful in the management of
      several retinal disorders, but causes significant changes in AL. Arch Ophthalmol.
      2000;118:965-968

PMID- 10900113
TI  - Myocilin and glaucoma: A TIGR by the tail?
AB  - In 1997, Stone and 14 colleagues from 7 laboratories reported the identification
      of a gene (TIGR) associated with juvenile open-angle glaucoma (JOAG). Screening
      of adults with primary open-angle glaucoma (POAG) revealed that about 4% also
      carried a mutation of the coding region of this gene. The mutations were found
      through genetic linkage analysis of families with JOAG. Juvenile open-angle
      glaucoma was a logical starting point in the search for genetic causes of open
      angle glaucoma: it shows a strong autosomal-dominant inheritance pattern, occurs
      at an early age, demonstrates obvious phenotypic signs (dramatic elevation of
      intraocular pressure and subsequent optic nerve damage), and is likely to be
      found in multiple generations as parents of affected children are still living.
      These factors, however, also serve to distinguish it from adult-onset POAG, which
      generally has a lower intraocular pressure and a less severe course. The
      discovery of the actual gene represented a true advance over previous studies
      that had mapped the gene to a segment of a chromosome but did not identify the
      specific gene. How the mutant gene causes glaucoma is unknown and is the subject
      of intense research. To date, 26 mutations in the TIGR gene sequence (the term
      TIGR has been replaced by the term myocilin, abbreviated MYOC) have been
      described, all associated with either JOAG or adult-onset POAG. A correlation
      between specific mutations in MYOC and the clinical course of glaucoma has been
      found. Not all cases of JOAG or POAG have mutations in the MYOC gene, however,
      indicating that more discoveries of other genes are yet to come. Arch Ophthalmol.
      2000;118:974-978

PMID- 10900112
TI  - Familial cavernous hemangioma: An expanding ocular spectrum.
AB  - OBJECTIVE: To describe the clinical and genetic findings in a family with
      multiple cases of cavernous hemangiomas. DESIGN: Investigational clinical and
      genetic study in which 3 generations of a family consisting of 12 members were
      screened with magnetic resonance brain imaging, dilated ophthalmoscopic
      examination, and cutaneous survey coupled with linkage analysis to determine
      affected individuals and to better define manifestations of this neuro-oculo
      cutaneous syndrome. RESULTS: The proband had multiple cerebral cavernous
      hemangiomas and a choroidal hemangioma. Her son was found to harbor a retinal
      cavernous hemangioma. The proband's sister manifested a cerebral cavernous
      hemangioma, cutaneous hemangiomas, and a presumed choroidal hemangioma; her
      daughter demonstrated radiological findings suggestive of a cerebral cavernous
      hemangioma. The father of the proband demonstrated multiple, cutaneous
      hemangiomas. The remaining family members were free of lesions. The 7q locus
      could not be excluded as harboring the causative gene. CONCLUSIONS: This family
      may have a dominantly inherited neuro-oculo-cutaneous condition of cavernous
      hemangiomas with variable expressivity. The presence of choroidal hemangiomas in
      this phacomatosis has not been described previously to our knowledge. CLINICAL
      RELEVANCE: The presence of either retinal cavernous or choroidal hemangioma
      should alert the physician to search for features suggestive of systemic and
      familial involvement; either lesion may constitute the ocular component of the
      neuro-oculo-cutaneous phacomatosis, sometimes referred to as cavernoma multiplex.
      Arch Ophthalmol. 2000;118:969-973

PMID- 10900114
TI  - Cornea and external disease in the new millennium.

PMID- 10900115
TI  - Endophthalmitis after strabismus surgery.

PMID- 10900116
TI  - Adenocarcinoma of the esophagus presenting as orbital cellulitis.
AB  - A 56-year-old man was seen with signs and symptoms consistent with orbital
      cellulitis. Computed tomographic scan showed a localized bony defect in the
      sphenoid wing, on which a biopsy was performed through a lateral orbitotomy.
      Pathologic examination of the surgical specimen revealed mucinous adenocarcinoma,
      and metastatic workup revealed an extensive lower esophageal malignant neoplasm.
      Arch Ophthalmol. 2000;118:986-988

PMID- 10900117
TI  - Late closure of argon laser iridotomies following regrowth of iris pigment
      epithelium.

PMID- 10900118
TI  - Malignant melanoma arising from a large uveal melanocytoma in a patient with
      oculodermal melanocytosis.

PMID- 10900119
TI  - An infratemporal fossa foreign body presents as an infraorbital mass.

PMID- 10900120
TI  - Indwelling temporary retrobulbar catheter for long-lasting titratable local
      anesthesia.
AB  - OBJECTIVE: To evaluate an indwelling temporary retrobulbar catheter for
      repeatable injections of local anesthetics for long-lasting and titratable
      retrobulbar anesthesia in intraocular surgery. PARTICIPANTS: The prospective
      clinic-based study included 153 patients who underwent vitreoretinal surgery
      (n=111) or buckling procedures with cryocoagulation (n=34). The mean duration of
      surgery was 84.7 +/- 49.5 minutes (range, 25-310 minutes). Using commercially
      available retrobulbar needles with a diameter of 0.60 or 0.80 mm and a length of
      38 mm, 5 mL of 2% mepivacaine hydrochloride was injected. Through the same
      needle, a 28-gauge commercially available flexible catheter was introduced into
      the retrobulbar space. The needle was withdrawn and the catheter was fixed. When
      the patients started to feel pain during surgery, 2 mL of mepivacaine
      hydrochloride was reinjected through the catheter. RESULTS: Ten to 240 minutes
      after the start of the operation, 96 patients needed an intraoperative
      reinjection of mepivacaine after which they felt comfortable again. Forty-two
      patients needed a second reinjection of mepivacaine 30 to 270 minutes after the
      start of the operation, and 13 patients needed a third reinjection 45 to 145
      minutes after the start of surgery. Removal of the catheter after surgery was
      unremarkable. No infections were observed. Microbiologic examination results of
      the catheter tip were negative for organisms. Diplopia or other motility problems
      were not detected. Introduction and fixation of the catheter took less than 5
      minutes in all patients. CONCLUSIONS: An indwelling temporary retrobulbar
      catheter for repeatable intraoperative injections of local anesthetics is simple,
      effective, and useful, and in comparison with general anesthesia, it is a time
      saver for long-lasting and titratable local anesthesia in intraocular surgery.
      Arch Ophthalmol. 2000;118:996-1000

PMID- 10900121
TI  - Photo essay: anterior orbital myiasis caused by human botfly (Dermatobia
      hominis).

PMID- 10900122
TI  - Photo essay: combined hamartoma of the retina and retinal pigment epithelium in
      Gorlin syndrome.

PMID- 10900123
TI  - Old wine and new wine.

PMID- 10900124
TI  - Old wine and new wine

PMID- 10900125
TI  - Answers to crossword puzzle: july 2000

PMID- 10900126
TI  - Minor thiols cysteine and cysteinylglycine regulate the competition between
      glutathione and protein SH groups in human platelets subjected to oxidative
      stress.
AB  - Changes in the concentrations of protein-mixed disulfides (XS-SP) of glutathione
      (GSH), cysteine (CSH), and cysteinylglycine (CGSH) were studied in human
      platelets treated with diamide and t-BOOH in timecourse experiments (time range,
      1-30 min) in order to understand the contribution of minor thiols CSH and CGSH to
      the regulation of glutathione-protein mixed disulfides (GS-SP). Diamide was much
      more potent than t-BOOH in altering the platelet thiol composition of XS-SP
      (threshold dose: diamide, 0.03 mM; t-BOOH, 0.5 mM) and caused reversible XS-SP
      peaks whose magnitude was related to the concentration of free thiols in
      untreated cells. Thus maximum levels of GS-SP (8 min after 0.4 mM diamide) were
      about 16-fold higher than those of controls (untreated platelets, GS-SP = 0.374
      nmol/10(9) platelets), whereas those of CS-SP and CGS-SP were only 4-fold
      increased (untreated platelets, CS-SP = 0.112 nmol/10(9) platelets; CGS-SP =
      0.024 nmol/10(9) platelets). The greater effects of diamide with respect to t
      BOOH were explained on the basis of the activities of fast reactive protein SH
      groups for diamide and glutathione reductase (GR) and glucose-6-phosphate
      dehydrogenase (G-6-PDH) for t-BOOH. The addition of cysteine (0.3 mM, at 4 min)
      after treatment of platelets with 0.4 mM diamide increased the rate of reversal
      of GS-SP peaks to normal values, but also caused a relevant change in CGS-SP with
      respect to that of platelets treated with diamide alone. An increased gamma
      glutamyltranspeptidase activity was found in platelets treated with diamide.
      Moreover, untreated platelets were found to release and hydrolyze GSH to CGSH and
      CSH. Ratios of thiols/disulfides (XSH/XSSX) and activities of GR and G-6PDH were
      also related to a high reducing potential exerted by GSH but not by minor thiols.
      The lower mass and charge of minor thiols is a likely requisite of the regulation
      of GS-SP levels in platelets.

PMID- 10900127
TI  - Positively charged residues within the iron-sulfur cluster loop of E. coli MutY
      participate in damage recognition and removal.
AB  - Escherichia coli MutY is an adenine glycosylase involved in base excision repair
      that recognizes OG:A (where OG = 7, 8-dihydro-8-oxo-2'-deoxyguanosine) and G:A
      mismatches in DNA. MutY contains a solvent-exposed polypeptide loop between two
      of the cysteine ligands to the [4Fe-4S](2+) cluster, referred to as the iron
      sulfur cluster loop (FCL) motif. The FCL is located adjacent to the proposed
      active site pocket and has been suggested to be part of the DNA binding surface
      of MutY (Y. Guan et al., 1998, Nat. Struct. Biol. 5, 1058-1064). In order to
      investigate the role of specific residues within the FCL motif, we have
      determined the effects of replacing arginine 194, lysine 196, and lysine 198 with
      alanine on the enzymatic properties of MutY. The properties of the R194A, K196A,
      and K198A enzymes were also compared to the properties of mutated enzymes in
      which lysine residues near the active site pocket were replaced with alanine or
      glycine. Substrate recognition was evaluated using a duplex containing a 2'
      deoxyadenosine analog in a base pair opposite G or OG. These results indicate
      that removal of positively charged amino acids within the FCL and the active site
      compromise the ability of the enzyme to bind to the substrate analog. However,
      only the K198A enzyme exhibited a significant reduction (15-fold) of the rate of
      adenine removal from a G:A base pair-containing duplex. This is the first direct
      evidence that Lys 198 within the FCL motif of MutY has a role in specific damage
      recognition and removal. Furthermore, these results suggest that the FCL motif is
      intimately involved in the base removal process.

PMID- 10900128
TI  - Mammalian FKBP-25 and its associated proteins.
AB  - Soluble proteins from porcine brain were divided into two packs: (1) proteins
      which pass freely through CM52-cellulose, and (2) proteins retained on CM52. Each
      of these two packs of proteins was fractionated on preparative flat-bed
      isoelectrofocusing gel in the range of pH 2-12. Native FKBP-25 and its truncated
      forms were found among other proteins retained on CM52-cellulose. Immunoblotting
      with anti-FKBP-25 showed two bands in the range 27-30 kDa, one due to unmodified
      FKBP-25 and other due to FKBP-25 mixed with high-mobility group II protein (HMG
      II). Selective immunostaining with anti-FKBP-25 antibodies of proteins which were
      not retained on CM52-cellulose showed several bands within the range of pI 7-5
      and mass of 23 +/- 2 kDa. These fractions of proteins were next resolved on two
      dimensional gels and immunostained with anti-FKBP-25 antibodies. Six proteins in
      the pI range 7-5 were detected. Edman degradation of alpha-chymotrypsin digests
      of the major spot suggests that it contains the GTP-binding protein Rab5 co
      migrating with guanylyl kinase, whereas MALDI-TOF showed that a residual content
      of FKBP-25 may be also associated with these two proteins. A residual quantity of
      FKBP-25 was also associated with the phosphatidylethanolamine-binding protein
      which is abundant in the brain.

PMID- 10900129
TI  - Identification and characterization of a cDNA encoding cytochrome P450 3A from
      the fresh water teleost medaka (Oryzias latipes).
AB  - A new member of the CYP3A gene family has been cloned from the teleost fish
      medaka (Oryzias latipes) by reverse-transcriptase polymerase chain reaction (RT
      PCR). Degenerate primers homologous to highly conserved regions of known CYP3A
      sequences were used for initial RT-PCRs. Individual PCR products were cloned,
      sequenced, and identified as those belonging to the cytochrome P450 superfamily
      based on amino acid sequence similarity and the presence of the highly conserved
      heme-binding region. PCR products were subsequently used as probes to screen a
      complementary DNA library. A full-length cDNA clone was identified containing a
      1758-base-pair (bp) insert with an open reading frame encoding a single peptide
      of 500 amino acids. Comparisons of the deduced amino acid sequence to other known
      cytochrome P450 sequences indicate that this gene product is most similar to the
      CYP3A gene family and has been designated as CYP3A38 by the cytochrome P450
      nomenclature committee. Northern blot analysis identified two abundant CYP3A
      related transcripts in liver of both male and female adults and demonstrated
      quantitative differences in abundance according to gender. Similarly, Western
      blot analysis demonstrated the presence of two abundant cytochrome P450 related
      proteins in liver of both male and female adults. These results suggests that O.
      latipes contains multiple forms of CYP3A. Heterologous expression of CYP3A38 cDNA
      in HEK 293 cells produced a single protein that was reactive with anti-scup P450A
      (CYP3A) polyclonal antibody. Microsomes of HEK 293 cells expressing recombinant
      CYP3A38 protein actively catalyzed the hydroxylation of testosterone.

PMID- 10900130
TI  - The formation of stable fatty acid substrate complexes in prostaglandin H(2)
      synthase-1.
AB  - We have developed a protocol to purify apo-ovine (o) prostaglandin endoperoxide
      H(2) synthase-1 (PGHS-1) to homogeneity from ram seminal vesicles. The resulting
      apo enzyme can then be reconstituted with Co(3+)-protoporphyrin IX instead of
      Fe(3+)-protoporphyrin IX to produce a native-like, but functionally inert, enzyme
      suitable for the production of enzyme:fatty acid substrate complexes for
      biophysical characterization. Co(3+)-protoporphyrin IX reconstituted oPGHS-1
      (Co(3+)-oPGHS-1) displays a Soret band at 426 nm that shifts to 406 nm upon
      reduction. This behavior is similar to that of cobalt-reconstituted horseradish
      peroxidase and myoglobin and suggests, along with resonance Raman spectroscopy,
      that the Co(3+)-protoporphyrin IX group is one in a six-coordinate, cobalt(III)
      state. However, Co(3+)-oPGHS-1 does not display cyclooxygenase or peroxidase
      activity, nor does the enzyme produce prostaglandin products when incubated with
      [1-(14)C]arachidonic acid. The cocrystallization of Co(3+)-oPGHS-1 and the
      substrate arachidonic acid (AA) has been achieved using sodium citrate as the
      precipitant in the presence of the nonionic detergent N-octyl-beta-d
      glucopyranoside. Crystals are hexagonal, belonging to the space group P6(5)22,
      with cell dimensions of a = b = 181.69 A and c = 103.74 A, and a monomer in the
      asymmetric unit. GC-MS analysis of dissolved crystals indicates that unoxidized
      AA is bound within the crystals.

PMID- 10900132
TI  - Site-directed mutagenesis of the fructose 6-phosphate binding site of the
      pyrophosphate-dependent phosphofructokinase of Entamoeba histolytica.
AB  - Attempts to define the active site of pyrophosphate-dependent phosphofructokinase
      (PPi-PFK) using homology modeling based on the three-dimensional structure of the
      ATP-dependent PFKs from bacteria have been frustrated by low sequence identity
      between PPi- and ATP-PFKs in their carboxyl terminal halves. In the current
      study, alanine scanning mutagenesis of residues in the carboxyl terminal half of
      the PPi-PFK of Entamoeba histolytica coupled with comparative sequence analysis
      and computational modeling is used to identify residues that contribute to
      fructose 6-phosphate (fructose 6-P) binding. Of seven alanine mutants that were
      generated by site-directed mutagenesis, Arg377, Ser392, Arg405, Lys408, His415,
      His416, and Arg423, only the last mutant, Arg423Ala, was found to have
      dramatically lower affinity for fructose 6-P. Mutation of Arg 423 decreased
      k(cat) by 10,000-fold and decreased apparent affinity for fructose 6-P by 126
      fold, while the K(m) for PPi increased only 4-fold. The second greatest effect
      was seen with Arg377Ala, which had a nearly 10-fold decrease in apparent affinity
      and an approximate 60-fold decrease in maximal activity. Another residue, Tyr420,
      was chosen for mutagenesis by its complete identity in all other PPi-PFK. This
      residue and its homologue in Escherichia coli ATP-PFK, His249, were mutated and
      shown to be very important for substrate binding in both enzymes.

PMID- 10900133
TI  - Cholesterol flux between lipid vesicles and apolipoprotein AI discs of variable
      size and composition.
AB  - Reconstituted discoidal high-density lipoproteins (rHDLs) of apolipoprotein AI
      are able to induce leakage of the internal aqueous space of lipid vesicles (A.
      Tricerri et al., 1998, Biochim. Biophys. Acta 1391, 67-78) and such interaction
      depends on the cholesterol content of vesicles and rHDL as well as the rHDL size.
      With the aim of knowing if this rHDL/vesicle interaction plays some role in the
      cholesterol exchange, the time course for bidirectional radiolabeled cholesterol
      transfer between 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) vesicles and
      different sized rHDLs was measured. The results show that size increase in the
      rHDL decreases the rate constant for cholesterol transfer from POPC/cholesterol
      vesicles and that the initial presence of cholesterol in the vesicles results in
      an increased rate constant for cholesterol transfer from the rHDLs. This cannot
      be explained by a simple aqueous diffusion mechanism. The existing correlation
      between rHDL/vesicle interaction and cholesterol transfer rate suggests that
      besides the aqueous diffusion, another mechanism involving the binding or
      interaction between donor and acceptor may occur. This fact may be of
      physiological relevance since the relative high affinity of small cholesterol
      poor discs for cell membranes could facilitate the cholesterol efflux, while the
      decreased membrane affinity as a consequence of cholesterol enrichment and
      increase in size would decrease the rate of transfer in the opposite direction.

PMID- 10900131
TI  - Molecular modeling and substrate specificity of discrete cruzipain-like and
      cathepsin L-like cysteine proteinases of the human blood fluke Schistosoma
      mansoni.
AB  - Adult Schistosoma mansoni blood flukes express two discrete cysteine proteinases,
      SmCL1 and SmCL2, both of which are related to the cathepsin L-like enzymes of the
      C1 family of peptidases. Our previous phylogenetic analysis indicated that SmCL1
      is more closely related to cruzipain from the parasitic protozoa Trypanosoma
      cruzi than to human cathepsin L, whereas the converse situation applies with
      SmCL2. To characterize their catalytic subsites and substrate specificities, we
      have now developed three-dimensional (3D) homology models of SmCL1 and SmCL2
      using the structure of cruzipain and cathepsin L. Eisenberg analysis of the 3D
      models revealed self-compatibility scores of 90.1 and 96.1 out of a possible
      score of 97.6 for SmCL1 and SmCL2, respectively, verifying the accuracy and
      utility of the models. Substrate preferences of recombinant SmCL1 and SmCL2 at
      positions P3, P2, and P1 conformed to the substrate specificity predicted by the
      models. In particular, SmCL1 and SmCL2 both exhibited high affinity (k(cat)/K(m))
      for substrates with hydrophobic residues at P2 including Z-Leu-Arg-NHMec (773.4
      and 548.5 mM(-1) s(-1), respectively), Boc-Val-Leu-Lys-NHMec (116.8 and 306.5 mM(
      1) s(-1)), and Z-Phe-Arg-NHMec (38.9 and 113.4 mM(-1) s(-1)). SmCL1 exhibited
      only a low affinity for the cathepsin B diagnostic substrate Z-Arg-Arg-NHMec
      while SmCL2 failed to cleave this substrate. The substrate specificities of SmCL1
      and SmCL2 were clearly differentiated with H-Leu-Val-Tyr-NHMec and Suc-Leu-Tyr
      NHMec since SmCL1 cleaved both efficiently (k(cat)/K(m) values of 51.9 and 41.1
      mM(-1) s(-1), respectively), whereas SmCL2 cleaved neither. The 3D models
      revealed that this difference in specificity was due to restrictions imposed on
      the S3 subsite of SmCL2 as a result of insertion of two amino acids vicinal to
      residue 60.

PMID- 10900134
TI  - Differences between Mg(2+) and transition metal ions in the activation of
      calcineurin.
AB  - Exogenous metal ion activation of calcineurin catalyzed hydrolysis of para
      nitrophenyl phosphate was kinetically characterized at 20, 25, 30, and 37 degrees
      C. Analysis yielded estimates for thermodynamic parameters for the activation of
      calcineurin by each of the metal ions. Values for DeltaG(Me)( degrees ) were
      varied with the best activators resulting in more stable enzyme-metal ion
      complexes and with DeltaG(Me)( degrees ) dominated by the entropic component.
      Mg(2+) was the only nontransition metal ion which supported significant activity
      and showed some distinct characteristics including a negative DeltaS(Me)( degrees
      ), suggesting that activation by Mg(2+) may have resulted in a unique enzyme
      metal ion form. Circular dichroism showed that metal ions increased the alpha
      helical content of calcineurin, but little significant differences in the spectra
      were identified between using activating and nonactivating metal ions. Activating
      Mg(2+), but not nonactivating Ca(2+), did cause changes in the Fourier transform
      infrared photoacoustic spectrum of calcineurin compared to the spectrum of
      calcineurin with Mn(2+). Other metal ions, Co(2+) and Ni(2+), also caused no
      changes in the infrared spectrum. Possible explanations for these differences
      between Mg(2+) and transition metal ions in the activation of calcineurin are
      discussed.

PMID- 10900135
TI  - The Helicobacter pylori pyrB gene encoding aspartate carbamoyltransferase is
      essential for bacterial survival.
AB  - The production of defined isogenic Helicobacter pylori pyrB mutants was
      undertaken to investigate the role of aspartate carbamoyltransferase (encoded by
      pyrB) in the survival of the bacterium. The complete structural gene for
      aspartate carbamoyltransferase from H. pylori strain RU1 was cloned into
      Escherichia coli by complementation of a pyrB auxotrophic mutant to facilitate
      the construction of a pyrB-disrupted copy in E. coli. The H. pylori pyrB gene had
      high similarity to other bacterial pyrB genes, and the phylogenetic clustering
      with different species was consistent with functional characteristics of the
      ACTase. The transcription initiation site for H. pylori pyrB-mRNA was mapped 25
      bp upstream of the ATG start codon, and potential promoter regions were
      identified. In order to construct an isogenic pyrB H. pylori mutant by natural
      transformation and allelic exchange, the plasmid insert containing pyrB was
      disrupted by insertional mutagenesis of a chloramphenicol transferase gene
      cassette. In multiple transformations of H. pylori cells, no chloramphenicol
      resistant pyrB mutants were isolated. Successful mutagenesis of other H. pylori
      genes and PCR amplification of the recombined gene demonstrated that the ACTase
      negative mutants had been constructed by allelic exchange involving simultaneous
      replacement of the pyrB gene with the chloramphenicol-pyrB-disrupted copy. These
      findings suggested that the ACTase enzyme is essential for the survival of H.
      pylori.

PMID- 10900136
TI  - Characterization of the intracellular Ca(2+) pools involved in the calcium
      homeostasis in Herpetomonas sp. promastigotes.
AB  - Trypanosomatids of the genus Herpetomonas comprises monoxenic parasites of
      insects that present pro- and opisthomastigotes forms in their life cycles. In
      this study, we investigated the Ca(2+) transport and the mitochondrial
      bioenergetic of digitonin-permeabilized Herpetomonas sp. promastigotes. The
      response of promastigotes mitochondrial membrane potential to ADP, oligomycin,
      Ca(2+), and antimycin A indicates that these mitochondria behave similarly to
      vertebrate and Trypanosoma cruzi mitochondria regarding the properties of their
      electrochemical proton gradient. Ca(2+) transport by permeabilized cells appears
      to be performed mainly by the mitochondria. Unlike T. cruzi, it was not possible
      to observe Ca(2+) release from Herpetomonas sp. mitochondria, probably due to the
      simultaneous Ca(2+) uptake by the endoplasmic reticulum. In addition, a vanadate
      sensitive Ca(2+) transport system, attributed to the endoplasmic reticulum, was
      also detected. Nigericin (1 microM), FCCP (1 microM), or bafilomycin A(1) (5
      microM) had no effect on the vanadate-sensitive Ca(2+) transport. These data
      suggest the absence of a Ca(2+) transport mediated by a Ca(2+)/H(+) antiport. No
      evidence of a third Ca(2+) compartment with the characteristics of the
      acidocalcisomes described by A. E. Vercesi et al. (1994, Biochem. J. 304, 227
      233) was observed. Thapsigargin and IP(3) were not able to affect the vanadate
      sensitive Ca(2+) transport. Ruthenium red was able to inhibit the Ca(2+) uniport
      of mitochondria, inducing a slow mitochondrial Ca(2+) efflux, compatible with the
      presence of a Ca(2+)/H(+) antiport. Moreover, this efflux was not stimulated by
      the addition of NaCl, which suggests the absence of a Ca(2+)/Na(+) antiport in
      mitochondria.

PMID- 10900137
TI  - Antagonistic action of novel 1alpha,25-dihydroxyvitamin D(3)-26, 23-lactone
      analogs on 25-hydroxyvitamin-D(3)-24-hydroxylase gene expression induced by
      1alpha,25-dihydroxy-vitamin D(3) in human promyelocytic leukemia (HL-60) cells.
AB  - We have demonstrated that 1alpha,25-dihydroxyvitamin D(3)-26, 23-lactone analogs,
      (23S)- and (23R)-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactone (TEI-9647,
      TEI-9648, respectively), inhibit HL-60 cell differentiation induced by 1alpha,25
      dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], but not differentiation caused by
      all-trans retinoic acid (D. Miura et al., 1999, J. Biol. Chem. 274, 16392). To
      assess whether the antagonistic actions of TEI-9647 and TEI-9648 in HL-60 cells
      are related to 1alpha,25(OH)(2)D(3) breakdown, we investigated their effects on
      catabolism of 1alpha,25(OH)(2)D(3). In HL-60 cells, the C-24 but not the C-23
      side-chain oxidation pathway of 1alpha,25(OH)(2)D(3) has been reported. Here we
      demonstrate that 1alpha,25(OH)(2)D(3) was metabolized both to 24,25,26,27
      tetranor-1alpha,23-(OH)(2)D(3) and 1alpha,25(OH)(2)D(3)-26,23-lactone; thus HL-60
      cells constitutively possess both the 24- and the 23-hydroxylases. Metabolism of
      1alpha, 25(OH)(2)D(3) was strongly suppressed by 10(-7) M TEI-9647 or 10(-6) M
      TEI-9648. 1alpha,25(OH)(2)D(3) alone slightly induced 24-hydroxylase gene
      expression by 8 h with full enhancement by 24-48 h; this induction was inhibited
      by 10(-6) M TEI-9647 and 10(-6) M TEI-9648 (86.2 and 31.9%, respectively) 24 h
      after treatment. However, analogs of TEI-9647 and TEI-9648 without the 25-dehydro
      functionality induced 24-hydroxylase gene expression. These results indicate that
      TEI-9647 and TEI-9648 clearly mediate their stereoselective antagonistic actions
      independent of their actions to block the catabolism of 1alpha,25(OH)(2)D(3).
      Therefore, TEI-9647 and TEI-9648 appear to be the first antagonists specific for
      the nuclear 1alpha,25(OH)(2)D(3) receptor-mediated genomic actions of
      1alpha,25(OH)(2)D(3) in HL-60 cells.

PMID- 10900138
TI  - Escherichia coli requires the protease activity of FtsH for growth.
AB  - FtsH protease, the product of the essential ftsH gene, is a membrane-bound ATP
      dependent metalloprotease of Escherichia coli that has been shown to be involved
      in the rapid turnover of key proteins, secretion of proteins into and through the
      membrane, and mRNA decay. The pleiotropic effects of ftsH mutants have led to the
      suggestion that FtsH possesses an ATP-dependent chaperone function that is
      independent of its protease function. When considering FtsH as a target for novel
      antibacterials, it is necessary to determine which of these functions is critical
      for the growth and survival of bacteria. To address this, we constructed the FtsH
      mutants E418Q, which retains significant ATPaseactivity but lacks protease
      activity, and K201N, which lacks both protease and ATPase activities. These
      mutants were introduced into an E. coli ftsH knockout strain which has wild-type
      FtsH supplied from a plasmid under control of the inducible araBAD promoter.
      Since neither mutant would complement the ftsH defect produced in the absence of
      arabinose, we conclude that the protease function of FtsH is required for
      bacterial growth.

PMID- 10900139
TI  - The role of plasma membrane in bioreduction of two tetrazolium salts, MTT, and
      CTC.
AB  - Despite widespread use of various tetrazolium assays, the mechanisms of
      bioreduction of these compounds have not been fully elucidated. We investigated
      the capacity of tetrazolium salts to penetrate through intact cell plasma
      membranes. 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and 3-(4,5
      dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) tetrazolium salts
      appear to represent examples of species that are reduced by different mechanisms.
      We provide evidence suggesting that MTT readily crosses intact plasma membranes
      and is reduced intracellularly. MTT appears to be reduced by both plasma membrane
      and intracellular reductases; reducing cells are not damaged and remain
      metabolically active for at least 45 min. In contrast, CTC remains extracellular
      with respect to viable cells and thus requires plasma membrane permeable electron
      carrier to be reduced efficiently. However, reduction of CTC in the presence of
      an electron carrier inflicts damage on plasma membranes. The intracellular vs
      extracellular sites of reduction of tetrazolium salts were established on the
      basis of deposition of formazans. Crystals of formazan were detected using
      fluorescence or backscattered light confocal laser microscopy. We postulate that
      the capacity of a tetrazolium salt to cross intact plasma membranes constitutes
      an important experimental variable which needs to be controlled in order to
      correctly interpret the outcome of tetrazolium assays designed to measure
      cellular production of oxygen radicals, activity of mitochondrial, cytosolic, or
      outer membrane reductases, etc.

PMID- 10900140
TI  - Epitope mapping of rat cytochrome P450 2B1 using glutathione S-transferase-2B1
      fusion constructs.
AB  - We have previously produced 12 monoclonal antibodies (MAbs) against rat
      cytochrome P450(CYP)2B1, and 8 of these inhibit CYP2B1 catalytic activity to
      varying extents. Using competitive binding studies we showed that this collection
      of 12 MAbs recognize at least 6 spatially distinct epitopes. The complete coding
      sequence of CYP2B1 DNA in plasmid pSR-P450 was inserted into a glutathione S
      transferase (GST) expression vector pGEX-1lambdaT so that it was in frame with
      the GST gene. Expression of GST-CYP2B1 was detected with most of the MAbs in
      Western blots except those which were conformation-specific. Fourteen different
      constructs were then made using PCR with oligonucleotide primers having EcoRI
      sites at their ends and were introduced into the GST expression vector at the
      EcoRI site. Each fusion construct was expressed in Escherichia coli, subjected to
      SDS-PAGE, blotted, and probed individually with each MAb. MAbs, which inhibited
      catalytic activity and were mutually competitive in binding to CYP2B1 (viz.
      BEA33, BE44, BE45, and BE28), recognized several fusion constructs and by
      deduction recognized amino acids 250-261 in CYP2B1. Other antibodies inhibiting
      catalytic activity recognized amino acids 262-272 (BEF29) and 306-491 (BE46, B50,
      and BE49) on CYP2B1. Non-inhibitory MAbs BE26 and BE32 were mapped to region 380
      398 in CYP2B1. It was interesting to note that MAbs BEA33 and BE26, which also
      recognize spatially distinct epitopes on human CYP2E1 but not rat CYP2E1, had
      corresponding regions of high homology in human CYP2E1 but not rat CYP2E1.
      Identifying the epitopes recognized by this collection of MAbs will add to our
      understanding the sequences that may be important for producing inhibitory and
      specific antibodies to closely related antigens.

PMID- 10900141
TI  - Calcitriol upregulates expression and activity of the 1b isoform of the plasma
      membrane calcium pump in immortalized distal kidney tubular cells.
AB  - The plasma membrane calcium pump (PMCA) is ubiquitously expressed in calcium
      transporting epithelia. PMCA is encoded by four distinct genes (PMCA1-4) which
      can be further posttranscriptionally modified. PMCA1b is the only isoform of
      PMCA1 expressed in kidney and intestine. Calcitriol upregulates PMCA protein
      expression and activity and PMCA1 mRNA expression in the intestine. Calcitriol
      has a similar effect on kidney distal tubule PMCA activity in vivo but the
      cellular basis for this effect has not been studied. PMCA expression in Madin
      Darby bovine kidney (MDBK) cells, a distal kidney tubule cell line, was compared
      with a proximal tubule (LLC-PK1) and embryonic (HEK 293) kidney cell line. Only
      MDBK cells express PMCA1b mRNA and PMCA protein. In MDBK cells, calcitriol
      increased steady state expression of PMCA1b mRNA and protein and upregulated the
      functional activity of PMCA on calcium transport to a similar degree.
      Furthermore, calcitriol enhanced PMCA1b mRNA stability. These data are consistent
      with in vivo localization studies demonstrating the distal kidney tubule
      localization of PMCA protein. Furthermore, they indicate that calcitriol is an
      important regulator of PMCA activity in the kidney distal tubule by a pathway
      that includes translation and posttranscriptional modification of PMCA1b.

PMID- 10900142
TI  - Differential effect toward inhibition of papain and cathepsin C by recombinant
      human salivary cystatin SN and its variants produced by a baculovirus system.
AB  - Human salivary cystatin SN (CsnSN) is a member of the cystatin superfamily of
      cysteine proteinase inhibitors. In this study we used a baculovirus expression
      system to produce a full-length unaltered CsnSN and its variants. The variants
      were constructed with the changes in the three predicted proteinase-binding
      regions: the N-terminus (variant N(12-13), G12A-G13A), beta-hairpin loop I
      (variant L(56-58), Q56G-T57G-V58G) and beta-hairpin loop II (variant L(106-107),
      P106G-W107G). The secreted CsnSNs were purified using sequential spiral cartridge
      ultrafiltration and DE-52 radial flow chromatography. The purified proteins were
      examined for papain- and cathepsin C-inhibition. The wild-type CsnSN, and
      variants N(12-13) and L(106-107) bound tightly to papain (K(i) < 10 pM), whereas
      mutation in the loop I reduced binding affinity 5700-fold (K(i) = 57 nM). On the
      other hand, the wild-type CsnSN bound to cathepsin C less tightly (K(i) = 100
      nM). The mutation in the N-terminus or loop I reduced binding affinity by 16
      (K(i) = 1.6 microM)- and 19-fold (K(i) = 1.9 microM), respectively, while
      mutation in loop II resulted in an ineffective cathepsin C inhibitor (K(i) = 14
      microM). Collectively, these results suggest that the N-terminal G12-G13 residues
      of CsnSN are not essential for papain inhibition but play a role in cathepsin C
      inhibition; residues Q56-T57-V58 in the loop I are essential for both papain and
      cathepsin C inhibitions, and residues P106-W107 in the loop II are not important
      for papain inhibition but essential for cathepsin C inhibition. These results
      demonstrated that CsnSN variants have different effects toward different cysteine
      proteinases.

PMID- 10900143
TI  - The presence of an aqueous cavity in the proton-pumping pathway of the pyridine
      nucleotide transhydrogenase of Escherichia coli is suggested by the reaction of
      the enzyme with sulfhydryl inhibitors.
AB  - The pyridine nucleotide transhydrogenase of Escherichia coli carries out
      transmembrane proton translocation coupled to transfer of a hydride ion
      equivalent between NAD(+) and NADP(+). The membrane domain (domain II) of the
      enzyme is composed of 13 transmembrane helices. Previous studies (N. A. Glavas et
      al., Biochemistry 34, 7694-7702, 1995) have suggested that betaHis91 in
      transmembrane helix 9 is involved in the translocation pathway of protons across
      the membrane. In this study we have replaced amino acid residues on the same face
      of helix 9 as betaHis91 by single cysteine residues. We then examined the effect
      of the sulfhydryl inhibitors N-ethylmaleimide (NEM) and p
      chloromercuriphenylsulfonate (pCMPS) on enzyme activity and, in the case of
      [(14)C]NEM, as an enzyme label. The pattern of enzyme inhibition and labelling is
      consistent with the presence of an aqueous cavity through domain II from the
      cytosolic surface to the region of betaHis91. Residue betaAsn222 in helix 13,
      which appears also to be involved in the proton pathway across domain II, may
      interface with this aqueous cavity. A further series of mutants of betaGlu124 on
      helix 10 confirms the proposal (P. D. Bragg and C. Hou, Arch. Biochem. Biophys.
      363, 182-190, 1999) that this residue is involved in passive permeation of
      protons across domain II.

PMID- 10900144
TI  - Copurification of two holoenzyme-forming Calcium/Calmodulin-dependent protein
      kinase II isoforms as holoenzyme from porcine stomach.
AB  - Gastric acid secretion is conveyed by different signal transduction pathways,
      among these being the muscarinic receptor M(3)-mediated acid secretion. There is
      some evidence that CaMkinase II is involved in the acetylcholine-conveyed acid
      release. The apparent CaMkinase II-isoenzymes gamma and delta were purified as a
      holoenzyme from homogenate of pig gastric mucosa to apparent homogeneity. The
      chromatographical steps comprised cationic exchanger chromatography, calmodulin
      affinity chromatography, anionic exchanger chromatography, and gel filtration.
      The CaMkinase II showed an apparent molecular mass of 332 +/- 17.3 kDa composed
      of 59- and 61-kDa subunits. The latter was characterized by a polyclonal antibody
      directed against CaMkinase II-delta. The purified CaMkinase II showed
      autophosphorylation and Ca(2+)/calmodulin-dependent activation (K(0. 5) = 5 nM).
      Moreover, the enzyme showed inhibition by the potent CaMkinase II inhibitor KN-62
      in a dose-dependent manner. Addition of purified CaMkinase II inhibits the
      endogenous phosphorylation of a 105-kDa protein in the NaCl/Nonidet P-40 soluble
      fraction of the microsomal fraction of pig gastric mucosa. Our results suggest
      that CaMkinase II may regulate other protein kinases or phosphoprotein
      phosphatases, possibly by controlling acid production.

PMID- 10900145
TI  - Suppression of carbonic anhydrase III in rat liver by a dioxin-related toxic
      compound, coplanar polychlorinated biphenyl, 3, 3',4,4',5-pentachlorobiphenyl.
AB  - A coplanar polychlorinated biphenyl, 3,3',4,4',5-pentachlorobiphenyl (PenCB),
      significantly suppresses the expression of rat liver carbonic anhydrase III
      (CAIII), an enzyme which has recently been suggested to prevent from H(2)O(2)
      inducible apoptosis. Marked changes in the CAIII levels of liver cytosol were
      observed in rats following doses of PenCB ranging from 0.5 to 25 mg/kg body
      weight and maximum suppression was observed at a dose of 10 mg/kg. Northern
      analysis revealed that the level of CAIII mRNA in rat liver was dramatically
      reduced by PenCB treatment while only weak suppression was observed in pair-fed
      controls. Two AU-rich elements, considered as a destabilizing signal of mRNA,
      were found in the 3'-untranslated region of CAIII sequenced after reverse
      transcription-PCR and 3'-rapid amplification of the cDNA end. Dramatic decrease
      of CAIII in rat liver by PenCB could account for the suppression of the defense
      system for oxidative stress.

PMID- 10900146
TI  - Interaction of alcohol dehydrogenase with tert-butylhydroperoxide: stimulation of
      the horse liver and inhibition of the yeast enzymes.
AB  - Preincubation of horse liver alcohol dehydrogenase (HLADH) with the oxidative
      agent, tert-butyl hydroperoxide (tBOOH) results in a twofold stimulation of the
      ethanol dehydrogenase activity of this enzyme. This stimulation was dependent on
      tBOOH concentration up to 100 mM; above this concentration tBOOH did not further
      stimulate ethanol oxidation by HLADH. Active-site-directed reagents and classical
      ADH binary complexes were used to probe the possible mechanism of this activating
      effect. The rate and extent of stimulation by tBOOH is strongly reduced by binary
      complexes with NAD(+) or NADH, whose pyrophosphate groups bind to Arg-47 and Arg
      369. In contrast stimulation by tBOOH was not prevented by AMP or the sulfhydryl
      reagents dithiothreitol and glutathione, suggesting, respectively, a lack of role
      for Lys-228 and sulfhydryl group oxidation in the stimulation by tBOOH. In
      contrast to the liver enzyme, treatment of yeast ADH (YADH) with tBOOH
      irreversibly inhibited its ethanol dehydrogenase activity. Inhibition of YADH by
      tBOOH approximated first-order rate kinetics with respect to enzyme at fixed
      concentrations of tBOOH between 0.5 to 300 mM. Four -SH groups per molecule of
      YADH were modified by tBOOH, whereas only two -SH groups were modified in HLADH.
      The stimulation of HLADH by tBOOH is suggested to be due to destabilization of
      the catalytic Zn-coordination sphere and amino acids associated with coenzyme
      binding in the active site, while inactivation of YADH appears to be associated
      with -SH group oxidation by the peroxide.

PMID- 10900147
TI  - Role of the hinge loop linking the N- and C-terminal domains of the
      amidotransferase subunit of carbamoyl phosphate synthetase.
AB  - Carbamoyl phosphate synthetase from Escherichia coli catalyzes the formation of
      carbamoyl phosphate from bicarbonate, glutamine, and two molecules of ATP. The
      enzyme consists of a large synthetase subunit and a small amidotransferase
      subunit. The small subunit is structurally bilobal. The N-terminal domain is
      unique compared to the sequences of other known proteins. The C-terminal domain,
      which contains the direct catalytic residues for the amidotransferase activity of
      CPS, is homologous to other members of the Triad glutamine amidotransferases. The
      two domains are linked by a hinge-like loop, which contains a type II beta turn.
      The role of this loop in the hydrolysis of glutamine and the formation of
      carbamoyl phosphate was probed by site-directed mutagenesis. Based upon the
      observed kinetic properties of the mutants, the modifications to the small
      subunit can be separated into two groups. The first group consists of G152I,
      G155I, and Delta155. Attempts to disrupt the turn conformation were made by the
      deletion of Gly-155 or substitution of the two glycine residues with isoleucine.
      However, these mutations only have minor effects on the kinetic properties of the
      enzyme. The second group includes L153W, L153G/N154G, and a ternary complex
      consisting of the intact large subunit plus the separate N- and C-terminal
      domains of the small subunit. Although the ability to synthesize carbamoyl
      phosphate is retained in these enzymes, the hydrolysis of glutamine is partially
      uncoupled from the synthetase reaction. It is concluded that the hinge loop, but
      not the type-II turn structure of the loop per se, is important for maintaining
      the proper interface interactions between the two subunits and the catalytic
      coupling of the partial reactions occurring within the separate subunits of CPS.

PMID- 10900148
TI  - On the irreversible destruction of reduced nicotinamide nucleotides by hypohalous
      acids.
AB  - Degradation of the reduced pyridine nucleotides NMNH and NADH by HOCl involves
      two distinct stages: a fast reaction, k = 4.2 x 10(5) M(-1) s(-1), leads to
      generation of stable pyridine products (Py/Cl) with a strong absorption band at
      275 nm (epsilon = 12.4 x 10(3) M(-1) cm(-1) in the case of NMNH); secondarily, a
      subsequent reaction of HOCl, k = 3.9 x 10(3) M(-1) s(-1), leads to a complete
      loss of the aromatic absorption band of the pyridine ring. HOBr and HOI(I(2))
      react similarly. Apparent rate constants of the primary reactions of HOX species
      with NMNH at pH 7.2 increase in the order HOCl (3 x 10(5) M(-1) s(-1)) < HOBr(
      approximately 4 x 10(6) M(-1) s(-1)) < HOI(I(2))( approximately 6.5 x 10(7) M(-1)
      s(-1)). HOBr reacts fast also with the primary product Py/Br, k approximately 9 x
      10(5) M(-1) s(-1), while the reactions of HOI and I(2) with Py/I are slower,
      approximately 1.4 x 10(3) M(-1) s(-1) and >6 x 10(3) M(-1) s(-1), respectively.
      Halogenation of the amide group of NMN(+) by HOX species is many orders of
      magnitude slower than oxidation of NMNH. Taurine inhibits HOCl-induced oxidation
      of NADH, but HOBr-induced oxidation is not inhibited because the taurine
      monobromamine rapidly oxidizes NADH, and oxidation by HOI(I(2)) is not inhibited
      because taurine is inert toward HOI(I(2)). Also sulfur compounds (GSH, GSSG, and
      methionine) are less efficient in protecting NADH against oxidation by HOBr and
      HOI(I(2)) than against oxidation by HOCl. The results suggest that reactions of
      HOBr and HOI(I(2)) in a cellular environment are much more selectively directed
      toward irreversible oxidation of NADH than reactions of HOCl. It is noteworthy
      that the rather inert N-chloramines react with iodide to generate HOI(I(2)),
      i.e., the most reactive and selective oxidant of reduced pyridine nucleotides.
      NMR investigations show that the primary stable products of the reaction between
      NMNH and HOCl are various isomeric chlorohydrins originating from a
      nonstereospecific electrophilic addition of HOCl to the C5&dbond;C6 double bond
      of the pyridine ring. The primary products (Py/X) of NMNH all exhibit similar
      absorption bands around 275 nm and are hence likely to result from analogous
      addition of HOX to the C5&dbond;C6 bond of the pyridine ring. Since the Py/X
      species are stable and inert toward endogeneous reductants like ascorbate and
      GSH, they may generally be useful markers for assessing the contribution of
      hypohalous acids to inflammatory injury.

PMID- 10900149
TI  - The retinoid X receptor response element in the human aldehyde dehydrogenase 2
      promoter is antagonized by the chicken ovalbumin upstream promoter family of
      orphan receptors.
AB  - Two tandem sites in the aldehyde dehydrogenase 2 promoter (designated FP330-5'
      and FP330-3') that bind members of the nuclear receptor superfamily were recently
      identified. Antibodies against apolipoprotein regulatory protein (ARP-1) altered
      DNA-protein interactions in electrophoretic mobility shift assays using
      oligonucleotides representing either promoter site and rat liver or cultured cell
      nuclear extracts. In vitro-translated chicken ovalbumin upstream promoter
      transcription factor (COUP-TFI), ARP-1, or ErbA-related protein 2 (Ear2) bound
      both sites. In addition, ARP-1/RXR, COUP-TFI/RXR, and ARP-1/COUP-TFI heterodimers
      bound the FP330-3' site. Mutagenesis of the FP330-3' site indicated that a DR-1
      element was the preferred binding site for these factors. Transfected expression
      plasmids for these factors suppressed basal expression of reporter constructs
      containing the FP330-3' sites and the induction of the reporter by RXRalpha plus
      retinoic acid. Mutation of the two sites increased activity of a construct driven
      by 600 bp of the ALDH2 promoter in cell lines expressing COUP-TFs. The ALDH2
      FP330-3' site appears to represent a complex nuclear receptor response element
      that is activated by RXRs and HNF-4 but repressed by members of the COUP-TF
      family.

PMID- 10900150
TI  - The a subunit ala-217 --> arg substitution affects catalytic activity of F(1)F(0)
      ATP synthase.
AB  - A large number of mutations affecting the F(0) sector of Escherichia coli
      F(1)F(0) ATP synthase have been constructed and characterized. A subset of the
      missense mutations resulted in fully assembled enzyme complexes blocked in proton
      translocation and displaying marked decreases in ATP hydrolysis activity. The
      catalytic activities of one such mutant enzyme, a(ala-217-->arg), have been
      determined using both multisite and unisite catalysis conditions. As expected,
      the V(max) of the a(ala-217-->arg) enzyme was reduced under conditions of
      saturating substrate concentration. However, the F(0) sector amino acid
      substitution did not affect nucleotide occupancy of the noncatalytic sites.
      Moreover, the microscopic rate constants measured using unisite methods yielded
      no significant differences between the intact wild type F(1)F(0) ATP synthase and
      the a(ala-217-->arg) mutant enzyme. In general, the values for unisite activities
      in both preparations were very similar to numbers reported in the literature for
      E. coli F(1)-ATPase. The results suggest that the a(ala-217-->arg) substitution
      resulted in a defect in catalytic cooperativity and most likely altered the
      enzyme by inhibiting the rotational mechanism of F(1)F(0) ATP synthase.

PMID- 10900152
TI  - Good "negative results".

PMID- 10900151
TI  - Dissemination of peroxidative stress via intermembrane transfer of lipid
      hydroperoxides: model studies with cholesterol hydroperoxides.
AB  - Lipid hydroperoxides (LOOHs) can be generated in cells when cholesterol (Ch) and
      other unsaturated lipids in cell membranes are degraded under conditions of
      oxidative stress. If LOOHs escape reductive detoxification by glutathione
      dependent selenoperoxidases, they may undergo iron-catalyzed one-electron
      reduction to free radical species, thus triggering peroxidative chain reactions
      which exacerbate oxidative membrane damage. LOOHs are more polar than parent
      lipids and much longer-lived than free radical precursors or products.
      Accordingly, intermembrane transfer of LOOHs (analogous to that of unoxidized
      precursors) might be possible, and this could jeopardize acceptor membranes. We
      have investigated this possibility, using photoperoxidized [(14)C]Ch-labeled
      erythrocyte ghosts as cholesterol hydroperoxide (ChOOH) donors and unilamellar
      liposomes [e.g., dimyristoyl-phosphatidylcholine/Ch, 9:1 mol/mol] as acceptors.
      ChOOH material consisted mainly of 5alpha-hydroperoxide, a singlet oxygen adduct.
      Time-dependent transfer of ChOOH versus Ch at 37 degrees C was determined, using
      high-performance liquid and thin-layer chromatographic methods to analyze
      liposomal extracts for these species. A typical experiment in which the starting
      ChOOH/Ch mol ratio in ghosts was approximately 0.05 showed that the initial
      transfer rate of ChOOH was approximately 16 times greater than that of parent Ch.
      Using [(14)C]Ch as a reporter in liposome acceptors, we found that transfer
      acquired ChOOHs, when exposed to a lipophilic iron chelate and ascorbate, could
      trigger strong peroxidative chain reactions, as detected by accumulation of
      [(14)C]Ch oxidation products. These findings support the hypothesis that
      intermembrane transfer of ChOOHs can contribute to their prooxidant membrane
      damaging and cytotoxic potential.

PMID- 10900153
TI  - Prion diseases and the immune system.
AB  - Transmissible spongiform encephalopathies are caused by unusual infectious agents
      that are purported to contain a single type of macromolecule, a modified host
      glycoprotein. The term prion has been applied to this group of agents.
      Surprisingly, the immune system appears to behave as a Trojan's horse rather than
      a protective fortification during prion infections. Because prions seem to be
      essentially composed of a protein, PrP(Sc), identical in sequence to a host
      encoded protein, PrP(C), the specific immune system displays a natural tolerance.
      However, lymphoid organs are strongly implicated in the preclinical stages of the
      disease. Certain immunodeficient animals are resistant to prions after peripheral
      inoculation. In normal subjects, cells of the immune system support the
      replication of prions and/or allow neuroinvasion. A better understanding of these
      aspects of prion diseases could lead to immunomanipulation strategies aimed at
      preventing the spread of infectious agents to the central nervous system.

PMID- 10900154
TI  - A randomized trial of methotrexate in newly diagnosed patients with type 1
      diabetes mellitus.
AB  - The aim of this study was to determine whether low-dose, oral methotrexate
      therapy would prolong the remission phase at the onset of Type 1 diabetes. Ten
      newly diagnosed, nonacidotic, ICA-positive, Type 1 diabetics were randomly
      assigned to receive either methotrexate (5 mg/m(2)/week) or no immunosuppressive
      treatment. The study was not blinded and no placebo was given. Endogenous insulin
      production was assessed every 3 months by fasting and Sustacal-stimulated C
      peptide levels. Methotrexate therapy was not beneficial in prolonging islet
      survival as assessed by fasting and stimulated C-peptide levels. Insulin
      requirements were generally lower in the control group, and islet failure,
      determined by an insulin requirement of >0.7 u/kg/day, occurred earlier for those
      receiving MTX (P < 0.02). Side effects of methotrexate treatment were minimal.
      There was no benefit from methotrexate therapy, and methotrexate therapy was
      associated with an earlier increase in insulin requirements.

PMID- 10900155
TI  - Polymorphisms of HLA DQB1 CAR1/CAR2 and TNFalpha IR2/IR4 microsatellite markers
      in patients affected with Graves disease.
AB  - Graves disease is an autoimmune thyroid disorder in which HLA class I and II
      confer susceptibility in different ethnic groups. An allele-specific polymerase
      chain reaction was used to characterize the variation of the HLA-DQB1 CAR1/CAR2
      and TNFalpha markers located on chromosome 6 in 85 unrelated Tunisian patients
      affected with Graves disease and 148 healthy control subjects. In contrast to the
      results regarding TNFalpha alleles showing no difference between patients and
      controls (P = 0.904), the analysis of the HLA-DQB1 CAR1/CAR2 polymorphism showed
      a significant difference in its alleles (P < 0.0001). Nevertheless, no allele
      exhibited a predispositional effect on GD pathogenesis.

PMID- 10900156
TI  - Tumor infiltrating lymphocytes in melanoma comprise high numbers of T-cell
      clonotypes that are lost during in vitro culture.
AB  - Melanoma is generally accepted as being an antigenic tumor capable of eliciting T
      cell responses that, however, in most cases are inadequate to control tumor
      growth. Tumor-infiltrating lymphocytes (TIL) in melanoma lesions comprise
      clonotypic T cells, indicating the in situ recognition of melanoma-associated
      peptide epitopes. Cultured TIL have been studied in order to unveil
      characteristics of TIL and the interactions of TIL and melanoma cells. Whether in
      vitro cultured TIL mirrors the in situ situation has, however, been questioned.
      In the present study we have taken advantage of T-cell receptor clonotype mapping
      methodology to conduct a full and detailed analysis of the T-cell clonotypes in
      melanoma lesions and in corresponding lines of TIL established in vitro. All
      melanoma lesions and the corresponding TIL cultures comprised high numbers of T
      cell clonotypes, typically in the range of 40 to more than 60. The subsequent
      comparison of T-cell clonotypes present in the original lesions and in the
      corresponding T-cell lines established in vitro demonstrated that a very limited
      number of the T-cell clonotypes established in vitro are identical to the T-cell
      clonotypes expanded in situ. These results demonstrate that in situ T-cell
      clonotypes in melanoma are not readily expanded in vitro and that the majority of
      T-cell clonotypes present in cultured TIL are not present in situ.

PMID- 10900157
TI  - Transient decreases in human T cell proliferative responses following vaccinia
      immunization.
AB  - To further study the immunosuppression associated with virus infections, we
      analyzed the proliferative responses of serial PBMC samples obtained following
      vaccinia virus immunization. In four of five volunteers, responses to PHA, anti
      CD3, vaccinia virus, and recall antigens were markedly decreased at at least one
      time point between days 5 and 29 after vaccination. Responses to PHA were
      restored by the addition of IL-2 or irradiated autologous healthy PBMC in the two
      volunteers tested, suggesting that the proliferation defect is attributable to
      accessory cell dysfunction. In one donor, immobilized anti-CD3 failed to induce
      proliferation, but addition of immobilized anti-CD28 partially restored
      proliferation. These results indicate that vaccinia virus infection can
      transiently suppress proliferative responses of PBMC, in part by causing
      accessory cell dysfunction. Our findings extend the list of viral infections
      associated with systemic immunologic effects and demonstrate that suppression of
      proliferation can occur with localized virus infections.

PMID- 10900158
TI  - Molecular modeling of the Jak3 kinase domains and structural basis for severe
      combined immunodeficiency.
AB  - Hereditary severe combined immunodeficiency (SCID) includes a heterogeneous group
      of diseases that profoundly affect both cellular and humoral immune responses and
      require treatment by bone marrow transplantation. Characterization of the
      cellular and molecular bases of SCID is essential to provide accurate genetic
      counseling and prenatal diagnosis, and it may offer the grounds for alternative
      forms of treatment. The Jak3 gene is mutated in most cases of autosomal recessive
      T(-)B(+) SCID in humans. Jak3 belongs to the family of intracellular Janus
      tyrosine kinases. It is physically and functionally coupled to the common gamma
      chain, gammac, shared by several cytokine receptors. We have established the
      JAK3base registry for disease and mutation information. In order to study the
      structural consequences of the Jak3 mutations, the structure of the human Jak3
      kinase and pseudokinase domains was modeled. Residues involved in ATP and Mg(2+)
      binding were highly conserved in the kinase domain whereas the substrate binding
      region is somewhat different compared to other kinases. We have identified the
      first naturally occurring mutations disrupting the function of the human Jak3
      kinase domain. The structural basis of all of the known Jak3 mutations reported
      so far is discussed based on the modeled structure. The model of the Jak3 protein
      also permits us to study Jak3 phosphorylation at the structural level and may
      thus serve in the design of novel immune suppressive drugs.

PMID- 10900159
TI  - Derivation of diabetes-resistant congenic lines from the nonobese diabetic mouse.
AB  - Autoimmune diabetes is a polygenic disease process in man and rodents. To
      identify and characterize genes involved in the pathogenesis of diabetes in
      nonobese diabetic (NOD) mice, we initiated a repetitive backcross of diabetes
      resistant C57L/J mice onto the NOD strain. This breeding scheme was based on the
      premise that selection for the trait of disease resistance among genetically
      mixed mice could be used to maintain transmission of nonpermissive alleles from
      the diabetes-resistant strain at critical diabetes susceptibility loci. Each of
      the three recombinant congenic mouse lines derived by this strategy retains a
      unique constellation of C57L/J-derived DNA segments. Consistent with the
      involvement of different genetic loci, the pancreatic histology of disease
      resistant mice differs from that in NOD mice in a line-specific manner.
      Functional studies using these lines demonstrate that pathogenesis of autoimmune
      diabetes is a multistep process which can be blocked at a minimum of three
      critical, genetically determined points.

PMID- 10900160
TI  - Activation of human neutrophils by the air pollutant sodium sulfite (Na(2)SO(3)):
      comparison with immature promyelocytic HL-60 and DMSO-differentiated HL-60 cells
      reveals that Na(2)SO(3) is a neutrophil but not a HL-60 cell agonist.
AB  - Sulfite exposure can induce inflammatory responses characterized by an influx of
      neutrophils into the airways leading to lung malfunctions. Studies focusing on
      sodium sulfite (Na(2)SO(3))/neutrophil interactions have shown that this chemical
      possesses proinflammatory properties based on its ability to induce a respiratory
      burst. Information regarding how this chemical could alter other neutrophil
      responses/functions as well as its role on immature promyelocytic cells is
      currently lacking in the literature. In this study, we report that Na(2)SO(3) can
      induce tyrosine phosphorylation events in human neutrophils but not in both HL-60
      and HL-60 + DMSO. As a positive control, GM-CSF was found to induce tyrosine
      phosphorylation of a particular protein of 120-130 kDa in both HL-60 and HL-60 +
      DMSO cells testifying that these cells were responsive. In addition, we report
      that Na(2)SO(3) does not alter neutrophil phagocytosis and that this chemical
      increases the release of the proinflammatory cytokine IL-8 but not TNF-alpha.
      Paradoxically, we found that Na(2)SO(3) acts as a potent inhibitor of de novo
      neutrophil protein synthesis in a concentration-dependent fashion (0.1, 1, or 10
      mM) as assessed by SDS-PAGE from metabolically [(35)S]-labeled cells. In contrast
      to mature neutrophils, we found that Na(2)SO(3) does not modulate de novo protein
      synthesis in HL-60 cells treated with low concentrations (0. 1 or 1 mM) and that
      this pollutant was toxic at 10 mM as judged by a drastic decrease of total
      protein content stained with Coomassie blue. We conclude that Na(2)SO(3) can
      activate human neutrophils and that its proinflammatory potential is further
      supported by its ability to increase IL-8 production. In addition, our results
      clearly indicate that HL-60 and HL-60 + DMSO respond differently than mature
      human neutrophils to the inflammatory pollutant Na(2)SO(3). Extrapolation of data
      obtained with HL-60 (and/or HL-60 + DMSO) to neutrophils should be taken with
      caution. Our data obtained with Na(2)SO(3) are an example.

PMID- 10900161
TI  - Humoral and cell-mediated immunity in mice with genetic deficiencies of
      prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormone.
AB  - Prolactin (PRL), growth hormone (GH), insulin-like growth factor-I (IGF-I), and
      thyroid hormones have been proposed as critical immunoregulatory mediators, and
      their clinical use is being considered. The precise role played by each of these
      hormones in the generation of humoral and cell-mediated immune responses was
      assessed in a panel of mice with mutations that result in a selective reduction
      of PRL, GH, IGF-I, and/or thyroid hormone production. A surprising result, in
      view of previous studies indicating an immunoregulatory role for these hormones,
      was that all mice generated normal humoral and cell-mediated immune responses
      following challenge with T-independent and T-dependent antigens and with Listeria
      monocytogenes. A review of these findings in the context of previous data has
      resulted in the formulation of a working hypothesis proposing that these hormones
      act as anabolic and/or stress modulating mediators with effects on most cells,
      including those of the immune system. When considered in this context, it is
      possible to reconcile the contradictory data.

PMID- 10900162
TI  - Noncognate binding to histones of IgG from patients with idiopathic systemic
      lupus erythematosus.
AB  - The mechanism of attachment of circulating immune complexes (CIC) to glomerular
      basement membranes (GBM) has not yet been elucidated. Since it has been proposed
      that histone may be the ligand between GBM and DNA/anti-DNA CIC, we explored by
      ELISA and Western blots the nature of the interaction of IgG with histone on
      solid phase. Cognate binding of IgG anti-histone antibody was characteristically
      dependent on in its F(ab')(2) fragment and was inhibited by free histone. On the
      other hand, heat-aggregated IgG, a model for CIC, and IgG from most patients with
      idiopathic SLE had a characteristic noncognate binding behavior to histone: it
      was dependent on Fcgamma rather than on the F(ab')(2) fragment and was not
      effectively inhibited by free histones. Also, binding to histone of in vitro
      generated DNA/anti-DNA immune complexes was not dependent on DNA as a histone
      ligand, but on Fcgamma. Finally, there was good agreement between the binding of
      this IgG to histone and to C1q. We concluded that: (1) altered IgG and/or CIC
      bind to solid-phase-attached histone primarily through their Fcgamma and (2) CIC
      may mimic IgG antihistone antibodies in solid-phase immunoassays.

PMID- 10900163
TI  - Deficiency of human complement factor I associated with lowered factor H.
AB  - Deficiencies of factor I and/or factor H result in an increased consumption of C3
      and higher susceptibility to recurrent infections. Here we describe a case of
      human factor I deficiency and lowered factor H levels. C3 concentration was 50%
      lower than normal, the classical pathway-dependent hemolytic activity was reduced
      to almost 30% of normal, and alternative pathway-dependent activity was
      completely absent. The killing by peripheral leukocytes of Candida albicans
      treated with deficient serum and the production of complement-dependent
      chemotactic factors were reduced in the proband's serum when compared with normal
      serum. Finally, we observed that C3 antigen present in the proband's serum has a
      different electrophoretic mobility than native C3 (most likely C3b), confirming
      the deregulation of complement activation due to the lack of regulatory proteins
      factors I and H. The impaired complement system described in this case, the first
      of its kind described in a Chile, explains the higher susceptibility to
      infections found in the proband.

PMID- 10900164
TI  - Many pathways to cardiac hypertrophy.

PMID- 10900166
TI  - Fas ligand-deficient mice display enhanced leukocyte infiltration and intima
      hyperplasia in flow-restricted vessels.
AB  - Fas ligand (FasL) is a death factor that induces apoptosis in Fas-bearing cells.
      To explore the role of FasL in vascular lesion formation, we analysed leukocyte
      infiltration and lesion formation in a flow-restriction model of vascular injury
      that results in neointima formation in the presence of intact endothelium. The
      left common carotid arteries of wild-type and FasL-deficient (gld) mice were
      ligated just proximal to the carotid bifurcation. Three days after the ligation,
      T lymphocyte and macrophage infiltration into the common carotid artery was
      notably enhanced in the gld mice relative to the wild-type C57BL/6J mice. Four
      weeks after the ligation, the common carotid arteries developed neointima-like
      lesions consisting primarily of alpha -smooth muscle actin-positive cells beneath
      an endothelial cell monolayer. Neointima formation was greater in the gld mice
      than in wild-type mice. These data provide mouse genetic evidence suggesting that
      Fas-mediated cell death can function to restrict inflammation and intimal
      hyperplasia during vascular remodelling.

PMID- 10900165
TI  - Cardiotrophin-1 phosphorylates akt and BAD, and prolongs cell survival via a PI3K
      dependent pathway in cardiac myocytes.
AB  - Growth factors and cytokines trigger survival signaling in a wide variety of cell
      systems, including cardiac myocytes. Participation of the phosphatidylinositol 3
      OH kinase (PI3K)/Akt pathway in survival signaling has already been described in
      some cell types, but its involvement in the survival of cardiac myocytes is as
      yet unknown. Recently, CT-1, an interleukin 6-related cytokine, was shown to have
      survival-promoting, anti-apoptotic effects on cultured cardiac myocytes. However,
      roles of PI3K-dependent pathways in this signaling have not been elucidated. In
      the present study, therefore, we examined the participation of the PI3K/Akt
      pathway in CT-1-induced, survival-promoting signaling in cultured ventricular
      myocytes. It was found that CT-1 phosphorylated and activated Akt, and the effect
      was blocked by the PI3K inhibitors LY294002 and wortmannin. CT-1 also
      phosphorylated the pro-apoptotic factor, BAD, and the BAD phosphorylation was
      inhibited by LY294002, suggesting that phosphorylation of BAD is one of the key
      events by which the PI3K/Akt pathway mediates CT-1-induced survival signaling.
      Further, CT-1 PI3K-dependently prolonged the survival of serum-starved
      ventricular myocytes by preventing apoptosis. In summary, our findings show that
      PI3K-dependent survival signals contribute to CT-1-mediated ventricular myocyte
      survival. In vivo, the death of ventricular myocytes leads to heart failure, and
      downregulation of survival signals and/or augmentation of pro-apoptotic signals
      are likely to be important components of disease processes. Thus, the extent to
      which CT-1 and the PI3K/Akt pathway mitigate such pathological processes, in
      vivo, is an important question for the future.

PMID- 10900167
TI  - Doxorubicin represses CARP gene transcription through the generation of oxidative
      stress in neonatal rat cardiac myocytes: possible role of serine/threonine kinase
      dependent pathways.
AB  - Doxorubicin (Dox), an anthracyclin antineoplastic agent, causes dilated
      cardiomyopathy. CARP has been identified as a nuclear protein whose mRNA levels
      are exquisitely sensitive to Dox. In this study we investigated the molecular
      mechanisms underlying the repression of CARP expression by Dox in cultured
      neonatal rat cardiac myocytes. Dox (1 micromol/l)-mediated decrease in CARP mRNA
      levels was strongly correlated with BNP but not with ANP mRNA levels. Hydrogen
      peroxide scavenger catalase (1 mg/ml) but not hydroxyl radical scavengers
      dimethylthiourea (10 mmol/l) or mannitol (10 mmol/l) blunted the Dox-mediated
      decrease in CARP and BNP expression. Superoxide dismutase inhibitor
      diethyldithiocarbamic acid (10 mmol/l), which inhibits the generation of hydrogen
      peroxide from superoxide metabolism, attenuated the repression. PD98059 (MEK1
      inhibitor, 50 micromol/l), SB203580 (p38 MAP kinase inhibitor, 10 micromol/l),
      calphostin C (protein kinase C (PKC) inhibitor, 1 micromol/l), non-selective
      protein tyrosine kinase inhibitors genistein (50 micromol/l) or herbimycin A (1
      micromol/l) failed to abrogate the downregulation of CARP and BNP expression by
      Dox. In contrast, H7 (30 micromol/l), a potent inhibitor of serine/threonine
      kinase, significantly blocked Dox-mediated downregulation of CARP and BNP
      expression. Transient transfection of a series of 5'-deletion and site-specific
      mutation constructs revealed that M-CAT element located at -37 of the human CARP
      promoter mediates Dox-induced repression of CARP promoter activity. These results
      suggest that a genetic response to Dox is mediated through the generation of
      hydrogen peroxide, which is selectively linked to the activation of H7-sensitive
      serine/threonine kinase distinct from PKC and well characterized mitogen
      activated protein (MAP) kinases (ERK and p38MAP kinase). Furthermore, our data
      implicated M-CAT element as a Dox-response element within the CARP promoter in
      cardiac myocytes.

PMID- 10900168
TI  - kappa -opioid receptor stimulation induces arrhythmia in the isolated rat heart
      via the protein kinase C/Na(+)-H(+)exchange pathway.
AB  - The present study attempted to determine whether the protein kinase C (PKC)/Na(+)
      H(+)exchange (NHE) pathway would mediate the arrhythmogenic action of kappa 
      opioid receptor (OR) stimulation. We first determined the effects of U50,488H, a
      selective kappa -OR agonist, on PKC activity and cardiac rhythm in the isolated
      perfused rat heart, and intracellular pH (pH(i)), and Ca(2+)([Ca(2+)](i)) and
      Na(+)([Na(+)](i)) concentrations in the isolated ventricular myocyte. At 5-40
      microm U50,488H concentration dependently increased the particulate PKC activity
      and pH(i), and induced arrhythmia. 40 microm U50,488H also increased
      [Na(+)](i)and [Ca(2+)](i). The arrhythmogenic effects of 40 microm U50,488H were
      abolished by nor-binaltorphimine, a selective kappa -OR antagonist. Blockade of
      PKC and NHE with respective blockers, 1 microm bisindolylmaleimide I or 0.5
      microm calphostin C, and 1 microm 5-[N -methyl- N -isobutyl]amiloride or 1 microm
      5-([N -ethyl- N -isopropopyl]amiloride, abolished and significantly attenuated,
      respectively, the effects of kappa -OR stimulation on pH(i), [Na(+)](i)and
      [Ca(2+)](i), and arrhythmia. To determine the role of pH(i), we observed U50,488H
      induced arrhythmia at pH(i)6.8. At this pH(i), the pH(i)increased gradually both
      in the presence and absence of 40 microm U50,488H to a similar extent. While the
      increase in response to U50,488H was significantly less at pH(i)6.8 (from 0.09 to
      0.10) than that at pH(i)7.1 (from 0.01 to 0.18), the arrhythmia induced by the
      agonist was the same at both high and low pHs. On the other hand, 5 microm
      monensin, a sodium ionophore, increased [Na(+)](i)and [Ca(2+)](i), and induced
      arrhythmia to similar extents as U50,488H. PKC and NHE inhibitors, that
      significantly attenuated the effects induced by U50,488H, had no effect on those
      induced by monensin. In conclusion, kappa -OR stimulation induces arrhythmia via
      PKC/NHE. [Na(+)](i)and [Ca(2+)](i), but not pH(i), may be directly responsible
      for arrhythmia induced by kappa -OR stimulation.

PMID- 10900169
TI  - Oxidative stress increases synthesis of big endothelin-1 by activation of the
      endothelin-1 promoter.
AB  - Modulation of the biosynthesis of the vasoconstrictor peptide endothelin-1 by
      oxygen-derived free radicals generated by xanthine oxidase or hydrogen peroxide
      was studied in cultured endothelial cells. Endothelin-1 metabolism was
      investigated at the level of endothelin-1 promoter, preproendothelin-1 mRNA and
      intracellular big endothelin-1. Endothelin-1 mRNA, as characterized by Northern
      blotting, was increased both time- and dose-dependently by xanthine oxidase to up
      to 500% above baseline. Analysis of endothelin-1 promoter activity using a
      construct containing 1329 bp of the endothelin-1 promoter revealed that promoter
      activity was increased up to eight-fold by incubation with xanthine oxidase.
      Specificity was ascertained by co-incubation with superoxide dismutase and
      catalase leading to inhibition of the effect of xanthine oxidase. A significant
      contribution of nitric oxide was ruled out, since NOS III-mRNA transcription
      remained unchanged and l -NAME did not significantly alter endothelin-1 promoter
      activity. Synthesis of intracellular big endothelin-1 protein was increased dose
      dependently by xanthine oxidase. Our results indicate that oxidative stress leads
      to increased endothelial synthesis of big endothelin-1, which is a previously
      unknown mechanism and may help to understand the detrimental association of
      increased oxidative stress and elevated endothelin-1 levels in pathophysiological
      conditions promoting atherosclerosis.

PMID- 10900170
TI  - Magnesium-calcium exchange in cardiac troponin C bound to cardiac troponin I.
AB  - Understanding the process of Ca(2+)/Mg(2+)exchange during muscle excitation and
      relaxation is fundamental to elucidating the mechanism of Ca(2+)-regulated muscle
      contraction. During the resting phase, the C-domain of cardiac troponin C may be
      occupied by either Ca(2+)or Mg(2+). Here, complexes of recombinant cardiac
      troponin C(81-161) and the N terminus of cardiac troponin I, representing
      residues 33-80, were generated in the presence of saturating Mg(2+).
      Heteronuclear multi-dimensional nuclear magnetic resonance experiments were used
      to obtain backbone assignments of the Mg(2+)-loaded complex. In the presence of
      cardiac troponin I, the affinity of site IV for Mg(2+)is increased. Comparison of
      Mg(2+)and Ca(2+)-loaded complexes reveals that chemical shift differences are
      primarily localized to metal-binding sites III and IV, defining positions within
      these sites that have distinct Ca(2+)/Mg(2+)conformations. The observed
      transition from the Mg(2+)-loaded to Ca(2+)-loaded form demonstrates that sites
      III and IV fill simultaneously with Ca(2+)displacing Mg(2+). However, even in the
      absence of excess Ca(2+), Mg(2+)does not readily displace Ca(2+)in the isolated
      binary complex. Thus, the Mg(2+)-loaded conformer may only represent a small
      fraction of the total cardiac troponin C found in the sarcomere.

PMID- 10900171
TI  - Phosphorylation of elk-1 by MEK/ERK pathway is necessary for c-fos gene
      activation during cardiac myocyte hypertrophy.
AB  - Cardiac hypertrophy is associated with specific alterations in myocardial gene
      expression; however, the exact mechanisms responsible for altered gene expression
      are poorly defined. The goal of this study was to investigate whether signaling
      kinases that are activated during cardiac hypertrophy directly modulate
      transcription factor activity and regulate gene expression. In an effort to
      understand this process, we focused our studies on the transcriptional activation
      of c-fos gene through the serum response element (SRE)/ternary complex factor
      (TCF) element, during phenylephrine-induced myocyte hypertrophy. In this study,
      we show that phosphorylated Elk-1, a TCF, binds to c-fos SRE and its binding to
      SRE is increased upon phenylephrine stimulation. Phenylephrine treatment
      activates phosphorylation of Elk-1 in the nucleus within five minutes and Elk-1
      dependent transcriptional activation is abolished by inhibitors selective for
      MEK/ERK kinases. These studies implicate that phosphorylation of Elk-1 by ERK
      kinase pathway is important for early gene activation during phenylephrine
      induced myocyte hypertrophy.

PMID- 10900172
TI  - Matrix metalloproteinase-1 expression by interaction between monocytes and
      vascular endothelial cells.
AB  - There is accumulating evidence of complicated interactions among vascular cells,
      i.e. endothelial cells, smooth muscle cells and monocytes/macrophages, in the
      regulation of vascular function and remodeling. We have investigated the
      mechanisms responsible for matrix metalloproteinase (MMP)-1 expression by
      interactions between monocytes and vascular endothelial cells. THP-1 cells (human
      monocytic cell line) and human umbilical vein endothelial cells (HUVECs) were
      cocultured. MMP-1 levels in the culture medium were measured by enzyme-linked
      immunosorbent assays. Collagenolytic activity in the culture medium was measured
      by fluorescence labeled-collagen digestion. Immunohistochemistry using an anti
      MMP antibody was carried out to determine which types of cell produce MMP-1. The
      addition of THP-1 cells to HUVECs for 48 h induced increases in MMP-1 levels and
      collagenolytic activity, which were 5- and 2-fold relative to those of HUVECs
      alone, respectively. A separate coculture experiment revealed that direct contact
      of THP-1 cells and HUVECs contributed to enhanced MMP-1 production in the
      cocolture. Immunohistochemical analysis revealed that both types of cell produce
      MMP-1 in the coculture. Neutralizing anti-interleukin-1 beta and tumor necrosis
      factor- alpha antibodies inhibited MMP-1 production by the coculture. The Src
      kinase and MEK inhibitors significantly inhibited MMP-1 production by the
      coculture. Coculture of THP-1 cells and HUVECs induced significant increases in
      Src and mitogen activated protein (MAP) kinase activities. Enhanced MMP-1
      expression induced by monocyte-endothelial cell interactions may play an
      important role in the pathogenesis of atherosclerosis and plaque rupture.

PMID- 10900174
TI  - Insulin-stimulated glucose transport is dependent on Golgi function in isolated
      working rat heart.
AB  - Insulin and epinephrine stimulate glucose uptake through distinct mechanisms. We
      tested the hypothesis that the golgi apparatus is involved in insulin-stimulated
      but not epinephrine-stimulated glucose transport and phosphorylation. METHODS: We
      perfused isolated working rat hearts with Krebs-Henseleit buffer containing [2
      (3)H]glucose (5 mmol/l, 0.05 microCi/ml) and Na-oleate (0.4 mmol/l). In the
      absence or presence of the inhibitor of golgi function, brefeldin A (30
      micromol/l), either insulin (1 mU/ml), epinephrine (1 micromol/l), or
      phenylephrine (100 micromol/l) plus propranolol (10 micromol/l, selective alpha 
      adrenergic stimulation) were added to the perfusate. RESULTS: Cardiac power was
      stable in all groups (between 8.56+/-0.61 and 10.4+/-1.11 mW) and increased (34%)
      with addition of epinephrine, but not with selective alpha -adrenergic
      stimulation. Insulin, epinephrine, and selective alpha -receptor stimulation
      increased glucose transport and phosphorylation (micromol/min/g dry wt, basal:
      1.19+/-0.13, insulin: 3.89+/-0.36, epinephrine: 3.46+/-0.27, alpha -stimulation:
      4.08+/-0.40). Brefeldin A increased basal glucose transport and phosphorylation
      and blunted insulin-stimulated but not epinephrine-stimulated glucose transport
      and phosphorylation. Selective alpha -stimulated glucose transport and
      phosphorylation was also blunted by brefeldin A. CONCLUSIONS: Both insulin and
      alpha -adrenergic stimulation result in glucose transporter translocation from a
      pool that requires golgi function. Stimulation with epinephrine results in
      glucose transporter translocation from a pool that does not require golgi
      function. The stimulating effects of the alpha -adrenergic pathway on glucose
      transport and phosphorylation are independent of changes in cardiac performance.

PMID- 10900173
TI  - Intact mitochondrial electron transport function is essential for signalling by
      hydrogen peroxide in cardiac myocytes.
AB  - Oxidative stress has been proposed as a mediator of cardiac injury during
      ischemia and reperfusion. We examined the signalling events initiated by short
      term exposure of cardiac myocytes to oxidative stress elicited by hydrogen
      peroxide. A potent stimulation of tyrosine phosphorylation was observed within 1
      to 2 min exposure to 1 m m hydrogen peroxide. Within 5 min, the ERK mitogen
      activated protein kinases (ERK MAPKs) were activated. This activation of ERK
      MAPKs was blocked by N-acetylcysteine (NAC), implicating a role for free radicals
      in the signalling events. NAC failed to inhibit ERK MAPK activation by the
      hypertrophic agent, phenylephrine, or hyperosmotic shock. Myxothiazol, an
      inhibitor of complex III of the mitochondrial electron transport chain, also
      inhibited ERK MAPK activation by hydrogen peroxide, but not by 12- O 
      tetradecanoylphorbol-13-acetate (TPA) or hyperosmotic shock. Myxothiazol
      completely inhibited the increase in tyrosine phosphorylated proteins observed
      with hydrogen peroxide treatment. A variety of inhibitors which act at different
      levels of the mitochondrial electron transport chain (rotenone,
      theonyltrifluoroacetone, antimycin A, cyanide) also inhibited activation of the
      ERK MAPKs by hydrogen peroxide but not TPA or hyperosmotic shock. These studies
      suggest a novel mechanism of regulation of the ERK MAPK pathway and oxidative
      stress signalling by hydrogen peroxide.

PMID- 10900175
TI  - Effect of hypertrophic cardiomyopathy mutations in human cardiac muscle alpha 
      tropomyosin (Asp175Asn and Glu180Gly) on the regulatory properties of human
      cardiac troponin determined by in vitro motility assay.
AB  - The properties of mutant contractile proteins that cause hypertrophic
      cardiomyopathy (HCM) have been investigated in expression studies and in mouse
      models. There is growing evidence that the precise isoforms of both the mutated
      protein and its interacting partners can qualitatively influence the effects of
      the mutation. We therefore investigated the functional effects of two HCM
      mutations in alpha -tropomyosin, Asp175Asn and Glu180Gly, in the in vitro
      motility assay using recombinant human alpha -tropomyosin, expressed with an N
      terminal alanine-serine extension (AStm) to mimic acetylation in vivo, and
      purified native human cardiac troponin. The expected switching off of
      reconstituted filament movement at pCa9, and switching on at pCa5, was observed
      with no difference in fraction of filaments motile or filament velocity, between
      wild-type and mutant filaments. However, we observed increased Ca(2+)sensitivity
      of fraction of filaments motile using the mutant tropomyosin compared to wild
      type (DeltaEC(50)+0.082+/-0. 019 pCa units for Asp175Asn and +0.115+/-0.021 for
      Glu180Gly). Indirect measurements using immobilized alpha -actinin to retard
      filament movement showed that filaments reconstituted with mutant AStm produced
      the same force as wild-type filaments. The results using human cardiac regulatory
      proteins reveal different effects of the HCM mutations in tropomyosin compared to
      studies using heterologous systems. By performing parallel experiments using
      either human cardiac or rabbit skeletal troponin we show that the cardiac
      specific phenotype of HCM mutations in alpha -tropomyosin is not the result of
      more marked functional changes when interacting with cardiac troponin.

PMID- 10900176
TI  - NF- kappa B independent suppression of endothelial vascular cell adhesion
      molecule-1 and intercellular adhesion molecule-1 gene expression by inhibition of
      flavin binding proteins and superoxide production.
AB  - Oxidation-reduction (redox) coupled mechanisms play an important role in the
      regulation of cell surface adhesion molecule expression. In endothelial cells
      membrane-bound NADH/NADPH oxidase is a significant source of intracellular
      superoxide (O(2)(-)) production. We explored the role of flavin containing
      proteins such as NADH/NADPH oxidase in the induction of vascular cell adhesion
      molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) gene
      expression in human aortic endothelial cells (HAECs) and human dermal
      microvascular endothelial cells (HMECs). Treatment of HAECs by tumor necrosis
      factor- alpha (TNF- alpha, 100 U/ml) for 1 h induced a 31% increase in O(2)(
      )production within 5 min as determined by lucigenin chemiluminescence analysis of
      whole cells (n=4, P<0.05). Pretreatment with the NADH/NADPH oxidase inhibitor
      diphenylene iodonium (DPI, 40 microm) for 1 h inhibited O(2)(-)production. DPI
      also inhibited TNF and LPS-induced VCAM-1 and ICAM-1 cell surface expression and
      TNF- alpha, LPS, or IL-1 beta induced VCAM-1 and ICAM-1 mRNA accumulation.
      However, DPI did not inhibit TNF- alpha -induced activation of nuclear NF- kappa
      B-like binding activity in HAECs and HMECs. Furthermore, DPI did not inhibit TNF-
      alpha induced transactivation of NF- kappa B-driven VCAM-1 and HIV-LTR promoter
      gene constructs in transiently transfected HMECs. These data suggest that flavin
      binding proteins such as NADH/NADPH oxidase can regulate VCAM-1 gene expression
      independent of NF- kappa B. Furthermore, intracellular O(2)(-)generation is not
      necessary for NF- kappa B activation or for transactivation of NF- kappa B driven
      promoters.

PMID- 10900177
TI  - Abnormalities in Ca(i)handling in myocytes that survive in the infarcted heart
      are not just due to alterations in repolarization.
AB  - Studies from our laboratory have defined alterations in Ca(i)handling in the non
      dialyzed subepicardial cells that have survived in the 5 day infarcted heart
      (IZs). To determine whether changes in the action potential profile contributed
      to the observed Ca(i)changes we have used a combined voltage clamp/epifluorescent
      technique to determine and compare changes in fura 2 ratios in IZs compared to
      those of epicardial cells from the non-infarcted canine hearts (NZs). We found
      that Ca(i)changes in voltage clamped IZs persisted. In NZs, Ca(i)transients
      showed the expected voltage dependence while IZs did not. To determine whether
      altered NaCa exchanger activity contributed to the observed changes in Ca(i)in
      IZs, we measured NaCa exchanger Ca(2+)fluxes (reverse and forward mode) and ionic
      currents in both cell types and under different Na(i)loads (10 and 20 m m). We
      found that there were no significant differences in resting, peak or magnitude of
      fura 2 ratio changes or in outward current densities between NZs and IZs even
      under the different Na(i)loads. Thus, we suggest that chronic up- or
      downregulation of the NaCa exchanger protein does not underlie observed
      Ca(i)changes in IZs. Additionally, Ca(2+)released with paced voltage steps
      represented 79% of that released by caffeine in NZs while, in IZs, caffeine
      releasable Ca(2+)was equivalent to that released with step depolarization. Thus,
      abnormalities in Ca(i)handling in IZs appear not to arise secondarily to changes
      in action potential configuration nor do they appear to be due to disease-induced
      alteations in NaCa exchanger function.

PMID- 10900178
TI  - Rate-dependency of action potential duration and refractoriness in isolated
      myocytes from the rabbit AV node and atrium.
AB  - During atrial fibrillation, ventricular rate is determined by atrioventricular
      nodal (AVN) conduction, which in part is dependent upon the refractoriness of
      single AVN cells. The aims of this study were to investigate the rate-dependency
      of the action potential duration (APD) and effective refractory period (ERP) in
      single myocytes isolated from the AV node and atrium of rabbit hearts, using
      whole cell patch clamping, and to determine the contribution of the 4
      aminopyridine (4-AP)-sensitive current, I(TO1)to these relationships in the two
      cell types. AVN cells had a more positive maximum diastolic potential (-60+/-1 v
      71+/-2 mV), lower V(max)(8+/-2 v 144+/-17 V/s) and higher input resistance [420+/
      46 v 65+/-7 MOmega (mean+/-s.eP<0.05 n=9-33)], respectively, than atrial
      myocytes. Stepwise increases in rate from 75 beats/min caused activation failure
      and Wenckebach periodicity in AVN cells (at around 400 beats/min), but 1:1
      activation in atrial cells (at up to 600 beats/min). Rate reduction from 300 to
      75 beats/min shortened the ERP in both cell types (from 155+/-7 to 135+/-11 ms in
      AVN cells [P<0.05, n=6] and from 130+/-8 to 106+/-7 ms in atrial cells [P<0.05,
      n=10]). Rate increase from 300 to 480 and 600 beats/min shortened ERP in atrial
      cells, by 12+/-4% (n=8) and 26+/-7% (n=7), respectively (P<0.05). By contrast,
      AVN ERP did not shorten at rates >300 beats/min. In atrial cells, rate reduction
      to 75 beats/min caused marked shortening of APD(50)(from 51+/-6 to 29+/-6 ms,
      P<0. 05). 4-AP (1 m m) significantly prolonged atrial APD(50)at 75 beats/min
      (P<0.05, n=7), but not at 300 or 400 beats/min. In AVN cells, in contrast, there
      was less effect of rate change on APD, and 4-AP did not alter APD(50)at any rate.
      4-AP also did not affect APD(90)or ERP in either cell type. In conclusion, a lack
      of ERP-shortening at high rates in rabbit single AVN cells may contribute to
      ventricular rate control. I(TO1)contributed to the APD(50)rate relation in
      atrial, but not AVN cells and did not contribute to the ERP rate relation in
      either cell type.

PMID- 10900179
TI  - Hyperlipidemia with hypoglycemia reduces myocardial oxygen utilization efficiency
      but not contractile function during coronary hypoperfusion.
AB  - This study was designed to determine changes in myocardial contractile function
      and fuel selection during moderate coronary hypoperfusion in the presence of
      elevated plasma free fatty acid (FFA) at normal and reduced blood glucose
      concentrations. Coronary perfusion pressure (CPP) was sequentially lowered from
      100 to 60, 50, and 40 mmHg in the left anterior descending coronary artery (LAD)
      of anesthetized, open-chest dogs. Regional glucose uptake (GU), fatty acid uptake
      (FAU), percentage segment shortening (%SS), and oxygen consumption (MV O(2)) were
      determined with normal arterial plasma FFA concentrations (Group 1) or with
      elevated FFA concentrations (Groups 2 and 3). In Group 3, glucose in the coronary
      perfusate blood was reduced from 3.53+/-0.36 to 0.15+/-0.03 m M by hemodialysis.
      In Group 1, FAU fell by 85% as CPP was lowered to 60 mmHg and remained depressed
      as CPP was reduced further; GU did not fall significantly. Hyperlipidemia in
      Group 2 did not alter GU at any CPP, but maintained FAU at baseline levels until
      CPP was lowered to 40 mmHg. At 40 mmHg CPP, myocardial function and metabolic
      variables were similar in Groups 1 and 2. In Group 3 at 40 mmHg, FAU increased
      four-fold and MV O(2)doubled v Groups 1 and 2, and GU fell to zero. Despite these
      metabolic changes, %SS in Group 3 was unchanged relative to Group 2. Addition of
      glucose to the dialysate prevented the effects of dialysis on FAU, GU, and MV
      O(2). Thus, preferential glucose oxidation sustains myocardial oxygen utilization
      efficiency [(heart rate x %SS x maximum left ventricular pressure)/MV O(2)]
      during hypoperfusion. Blocking preferential glucose oxidation by combined
      hyperlipidemia and hypoglycemia lowers oxygen utilization efficiency, but does
      not compromise myocardial contractile function.

PMID- 10900180
TI  - Isoenzyme-specific protein kinase C and c-Jun N-terminal kinase activation by
      electrically stimulated contraction of neonatal rat ventricular myocytes.
AB  - Previous studies from our laboratory and others indicate that contraction-induced
      mechanical loading of cultured neonatal rat ventricular myocytes produces many of
      the phenotypic changes associated with cardiomyocyte hypertrophy in vivo, and
      that these changes occur via the activation of serine-threonine protein kinases.
      These may include the extracellular regulated protein kinases (ERK1 and ERK2),
      the c-Jun N-terminal kinases (JNK1, JNK2, and JNK3), and one or more isoenzymes
      of protein kinase C. In this study, we assessed whether one or more of these
      kinases are activated by stimulated contraction, and whether activation was
      isoenzyme-specific. Low-density, quiescent cultures of neonatal rat ventricular
      myocytes were maintained in serum-free medium, or electrically stimulated to
      contract (3 Hz) for up to 48 h. ERK and JNK activation was assessed by Western
      blotting with polyclonal antibodies specific for the phosphorylated forms of both
      kinases. PKC activation was analysed by subcellular fractionation, detergent
      extraction, and Western blotting using isoenzyme-specific monoclonal antibodies.
      Stimulated contractile activity produced myocyte hypertrophy, as indicated by
      increased cell size, a 15+/-5% increase in total protein/DNA ratio, and induction
      of ANF and beta MHC gene transcription. Electrical pacing did not cause ERK1/2 or
      JNK1 activation, but increased JNK2 and JNK3 phosphorylation by;two-fold.
      Subcellular fractionation revealed a time-dependent increase in PKC delta, and to
      a much lesser extent PKC xi, in a Triton X-100-soluble membrane fraction within 5
      min of the onset of stimulated contraction. PKC alpha was not activated by
      electrical pacing. These results indicate that contraction-induced mechanical
      loading acutely activates some but not all of the specific isoenzymes of JNKs and
      PKCs in cardiomyocytes.

PMID- 10900181
TI  - Interactions of dynorphin A-(1-13) and nociceptin with cardiac D2 binding sites:
      inhibition of ischemia-evoked release of noradrenaline from synaptosomal
      mitochondrial fractions.
AB  - The effect of dynorphin A (Dyn A)-related peptides and nociceptin on the binding
      of the D2 receptor antagonist, [(3)H]raclopride, was examined in membrane
      preparations of rat heart. Non-linear regression saturation binding analysis of
      [(3)H]raclopride binding revealed the presence of a single high-affinity binding
      site with a K(d)of 4.1 n M and a B(max)of 220 fmol/mg protein. The D2
      stereospecificity of [(3)H]raclopride binding was demonstrated by competition
      experiments using two enantiomer pairs of antagonists. (+)-Butaclamol (IC(50):
      8.0 n M) and (-)-sulpiride (IC(50): 112.3 n M) were 27 000 and 24 times more
      potent than (-)-butaclamol (IC(50): >100 microm) and (+)-sulpiride (IC(50): 2666
      n M), respectively. Nociceptin and Dyn A-(1-13) were also potent inhibitors of
      the binding of [3H]raclopride with shallow inhibition curves that fitted best
      with two sites model. Their order of potency on the low affinity site [alpha -Neo
      endorphin>nociceptin>Dyn A-(2-13)>Dyn A-(1-13)>Dyn B>Dyn A-(6-10)] correlated
      well with their ability to inhibit the binding of [3H]nociceptin (r=0.82). The
      indirect nature of the inhibitory effects of the peptides on the D2 receptor was
      demonstrated by their inability to inhibit [(3)H]raclopride binding to a membrane
      preparation (Sf9 cells transfected with the human D2(long)receptor) that does not
      contain the ORL(1)receptor and the lack of effect of raclopride (0.1 n M-10
      microm) on both [(3)H]nociceptin and [(3)H]Dyn A-(1-13) binding. Isolated cardiac
      mitochondrial-synaptosomal fractions submitted to ischemic conditions (1 m M
      iodoacetate +2 m M NaCN, 5 min at 37 degrees C) released 10.9% of their content
      in preloaded [(3)H]noradrenaline ([(3)H]NA). Dyn A-(1-13) (10 microm), nociceptin
      (10 microm) and the selective D2 receptor agonist, quinpirole (10 microm) were
      potent blockers of the release of [(3)H]NA evoked by the ischemic conditions. The
      inhibitory effect of Dyn A-(1-13), nociceptin and quinpirole were antagonized by
      the selective D2 receptor antagonist, raclopride (10 microm); whereas naloxone,
      at a concentration (1 microm) known to affect the ORL(1)receptor, blocked the
      effects of the peptides but not those of quinpirole. The results demonstrate the
      presence of D2 receptors in rat heart and suggest that Dyn A-(1-13) and
      nociceptin modulate ischemia-induced NA release by a mechanism that involves the
      participation of both ORL(1)and D2 receptors.

PMID- 10900182
TI  - Homozygotes for a R869G mutation in the beta -myosin heavy chain gene have a
      severe form of familial hypertrophic cardiomyopathy.
AB  - Familial Hypertrophic Cardiomyopathy (FHC) is an autosomal dominant disease
      characterised by ventricular hypertrophy, with predominant involvement of the
      interventricular septum. It is a monogenic disease with a high level of genetic
      heterogeneity (nine genes and more than 110 mutations reported so far). We
      describe a family with a new R869G mutation in the beta -myosin heavy chain gene
      (MYH7). This mutation was found in the heterozygous status in both parents and in
      the homozygous status in the two children. A haplotype analysis on the MYH7 locus
      with microsatellite markers showed that the same haplotype is transmitted within
      the family, suggesting a founder effect. Clinically, the father was asymptomatic
      with mild left ventricular hypertrophy on echocardiography. The mother had a mild
      form of hypertrophic cardiomyopathy and remained asymptomatic until 60 years old
      when an atrial fibrillation occurred. For the two children, clinical diagnosis
      was performed at 12 and 8 years and atrial fibrillation occurred at 17 years. For
      both children, the evolution was characterized by left ventricle (LV) systolic
      dysfunction and a severe dilatation of the left atrium before 40 years of age.
      CONCLUSIONS: In this family, a new R869G mutation in the MYH7 gene was found.
      Interestingly, a mutation was found at the homozygous status for the first time
      in FHC. This finding suggests that this particular mutation is compatible with
      life, but for homozygous subjects, age at onset of symptoms was earlier and the
      disease much more severe than in the heterozygous subjects, suggesting a gene
      dose effect.

PMID- 10900183
TI  - Involvement of a p38 mitogen-activated protein kinase phosphatase in protecting
      neonatal rat cardiac myocytes from ischemia.
AB  - Our recent results showed that extended p38 mitogen-activated protein kinase
      (p38) activation during ischemia leads to cell death, at least partly through
      apoptosis, in neonatal rat cardiomyocytes. However, other studies have shown that
      p38 activation during a short preconditioning treatment protects cardiomyocytes
      from ischemic cell death. This suggests that the duration of p38 activation
      determines its cellular function and therefore inactivation of p38 by
      phosphatases may play an important role. In neonatal rat cardiomyocytes, we used
      the tyrosine phosphatase inhibitor, vanadate, to prevent p38 inactivation, thus
      extending the strength and length of p38 activation during ischemia. This
      resulted in higher susceptibility to cell death from ischemia in a dose-dependent
      manner and over time; the additional damage induced by vanadate was inhibited by
      SB203580, a selective inhibitor of p38. We conclude that a tyrosine phosphatase
      is inactivated during ischemia, resulting in prolonged p38 activation which
      causes cell death.

PMID- 10900184
TI  - Flow-activated Na(+)and K(+)Current in cardiac microvascular endothelial cells.
AB  - The patch-clamp technique was used to investigate the electrical response of
      cardiac microvascular endothelial cells to fluid stream applied through a
      microtube. The fluid stream induced a membrane current whose amplitude was
      dependent on flow rate. The I-V relationship of the flow-activated current showed
      a strong inward rectification and a reversal potential close to +30 mV, which
      gave a P(Na)/P(k)=3.47. The inward and outward components of the current nearly
      disappeared when extracellular Na(+)and internal K(+), respectively, were
      replaced by NMDG(+). Finally, the flow-activated current was fully blocked by 50
      microM Gd(3+)and La(3+). These results show that cardiac microvascular
      endothelial cells respond to mechanical stimulation associated with flow by
      increasing their permeability to Na(+)and K(+). This mechanism is suggested to
      contribute to ionic homeostasis at high heart rates and during post-ischaemic
      reperfusion.

PMID- 10900185
TI  - Uncertainties in predicting the demographic impact of AIDS.
AB  - A model giving the demographic impact of AIDS is analysed to examine the
      sensitivity of the projections when various complicating features are included.
      The model deals with age and sexual partner change rate as continuous variables
      and uses a device to specify arbitrary correlations between the ages of the
      people who form sexual partnerships. The device ensures consistency, in that the
      amount of partner formation is the same regardless of whether the partnerships
      are counted from the point of view of males or females. Arbitrary correlation
      between partner change rate and fertility is also permitted. The results show the
      uncertainty in model predictions that population growth will reduce over the next
      20 years to approximately zero in parts of East Africa severely affected by the
      AIDS epidemic. The main sources of uncertainty in the model predictions are
      assumptions concerning the correlation between ages in a partnership, the
      correlation between partner change rate and fertility, the incubation period of
      AIDS, and the variability of the female partner change rate.

PMID- 10900186
TI  - Identifying predator-prey processes from time-series.
AB  - The functional response is a key element in predator-prey models as well as in
      food chains and food webs. Classical models consider it as a function of prey
      abundance only. However, many mechanisms can lead to predator dependence, and
      there is increasing evidence for the importance of this dependence.
      Identification of the mathematical form of the functional response from real data
      is therefore a challenging task. In this paper we apply model-fitting to test if
      typical ecological predator-prey time series data, which contain both observation
      error and process error, can give some information about the form of the
      functional response. Working with artificial data (for which the functional
      response is known) we will show that with moderate noise levels, identification
      of the model that generated the data is possible. However, the noise levels
      prevailing in real ecological time-series can give rise to wrong identifications.
      We will also discuss the quality of parameter estimation by fitting differential
      equations to such time-series.

PMID- 10900187
TI  - A generalization of Pontryagin's maximum principle for dynamic evolutionary games
      among relatives.
AB  - We present two theorems that generalize Pontryagin's maximum principle to the
      setting of dynamic evolutionary games between genetically related individuals.
      The two theorems correspond to two types of interactions among individuals: patch
      structured populations in which individuals locally "play the field" and pairwise
      interactions. These generalizations can be used in the same way that Pontryagin's
      maximum principle is used and they are valid for diploid organisms under a single
      locus, diallelic genetic model. These generalizations involve an interesting,
      dynamic version of Hamilton's Rule from inclusive fitness theory. We illustrate
      how these theoretical results can be applied by modeling the evolution of
      lifetime resource allocation to growth and reproduction in an annual plant when
      there is competition for resources among related individuals.

PMID- 10900188
TI  - A coalescence approach to gene conversion.
AB  - In this paper we develop a coalescent model with intralocus gene conversion. Such
      models are of increasing importance in the analysis of intralocus variability and
      linkage disequilibrium. We derive the distribution of the waiting time until a
      gene conversion event occurs in a sample in terms of the distribution of the
      length of the transferred segment, zeta. We do not assume any specific form of
      the distribution of zeta. Further, given that a gene conversion event occurs we
      find the distribution of (sigma, tau), the end points of the transferred segment
      and derive results on correlations between local trees in positions chi(1) and
      chi(2). Among other results we show that the correlation between the branch
      lengths of two local trees in the coalescent with gene conversion (and no
      recombination) decreases toward a nonzero constant when the distance between
      chi(1) and chi(2) increases. Finally, we show that a model including both
      recombination and gene conversion might account for the lack of intralocus
      associations found in, e.g., Drosophila melanogaster.

PMID- 10900189
TI  - Optimal Bayesian foraging policies and prey population dynamics-some comments on
      Rodriguez-Girones and Vasquez.
AB  - In this paper we show the density-dependent harvest rates of optimal Bayesian
      foragers exploiting prey occurring with clumped spatial distribution. Rodriguez
      Girones and Vasquez (1997) recently treated the issue, but they used a patch
      leaving rule (current value assessment rule) that is not optimal for the case
      described here. An optimal Bayesian forager exploiting prey whose distribution
      follows the negative binomial distribution should leave a patch when the
      potential (and not instantaneous) gain rate in that patch equals the best long
      term gain rate in the environment (potential value assessment rule). It follows
      that the instantaneous gain rate at which the patches are abandoned is an
      increasing function of the time spent searching in the patch. It also follows
      that the proportion of prey harvested in a patch is an increasing sigmoidal
      function of the number of prey initially present. In this paper we vary several
      parameters of the model to evaluate the effects on the forager's intake rate, the
      proportion of prey harvested per patch, and the prey's average mortality rate in
      the environment. In each case, we study an intake rate maximizing forager's
      optimal response to the parameter changes. For the potential value assessment
      rule we find that at a higher average prey density in the environment, a lower
      proportion of the prey is taken in a patch with a given initial prey density. The
      proportion of prey taken in a patch of a given prey density also decreases when
      the variance of the prey density distribution is increased and if the travel time
      between patches is reduced. We also evaluate the effect of using predation
      minimization, rather than rate maximization, as the currency. Then a higher
      proportion of the prey is taken for each given initial prey density. This is
      related to the assumption that traveling between patches is the most risky
      activity. Compared to the optimal potential value assessment rule, the current
      value assessment rule performs worse, in terms of long-term intake rate achieved.
      The difference in performance is amplified when prey density is high or highly
      aggregated. These results pertain to the foraging patch spatial scale and may
      have consequences for the spatial distribution of prey in the environment.

PMID- 10900190
TI  - Adaptive feeding across environmental gradients and its effect on population
      dynamics.
AB  - This paper analyzes a consumer's adaptive feeding response to environmental
      gradients. We consider a consumer-resource system where resources are distributed
      among many discrete resource patches. Each consumer exhibits a feeding morphology
      allowing it to remove resources from a patch down to some threshold density (or
      level) before having to seek resources elsewhere. Assuming consumers trade off
      resource extraction with patch access and predation, we show that for a given
      environment there often exists a single evolutionarily stable feeding threshold
      and it is an evolutionary attractor. We then investigate how the population
      dynamics of the resource and the consumer change as the environment changes. Two
      cases are considered: (i) all consumers exhibit a fixed feeding threshold that is
      adaptive for an intermediate environment; and (ii) the consumer population adapts
      and adopts the evolutionarily stable feeding threshold associated with the
      current environment. In less harsh environments (i.e., environments where
      consumers experience a lower risk of predation, or environments where resource
      patches are more abundant) the adaptive consumer population is predicted to
      evolve so that resources within a patch are depleted to lower densities. We show
      that the change in consumer density due to environmental change can be rather
      different depending on whether or not the population can adapt. In some
      situations we observe that when the consumer's environment becomes harsher, the
      consumer population may increase in density before a rapid crash to extinction.
      This result has implications for monitoring and managing a population.

PMID- 10900191
TI  - Population persistence time under intermittent control in stochastic
      environments.
AB  - If there exists a critical population size above which environmental degradation
      becomes serious, the population should be suppressed or reduced upon reaching
      that level. Since population size control is accompanied by costs, a reduction in
      control frequency may be preferable from an economic viewpoint. Although this can
      be realized by decreasing the population size drastically in each control, such
      management may result in increased population extinction probability according to
      environmental stochasticity. The effects of population management on both mean
      population persistence time and management cost were analyzed theoretically using
      a diffusion process. The model showed the functional forms of both mean
      persistence time and control frequency explicitly; these decreased with an
      increasing number of individuals removed from the population in each control
      operation. Based on the analysis, indices representing management costs are
      proposed. Mean persistence time is generally an increasing function of the cost
      indices. Nevertheless, if the cost of each control increases with the number of
      individuals removed, even the most conservative management practice (continuous
      control) may not be overly expensive.

PMID- 10900192
TI  - Crystal structure of human frataxin.
AB  - Friedreich's ataxia, an autosomal recessive neurodegenerative disorder
      characterized by progressive gait and limb ataxia, cardiomyopathy, and diabetes
      mellitus, is caused by decreased frataxin production or function. The structure
      of human frataxin, which we have determined at 1.8-A resolution, reveals a novel
      protein fold. A five-stranded, antiparallel beta sheet provides a flat platform,
      which supports a pair of parallel alpha helices, to form a compact alphabeta
      sandwich. A cluster of 12 acidic residues from the first helix and the first
      strand of the large sheet form a contiguous anionic surface on the protein. The
      overall protein structure and the anionic patch are conserved in eukaryotes,
      including animals, plants, and yeast, and in prokaryotes. Additional conserved
      residues create an extended 1008-A(2) patch on a distinct surface of the protein.
      Side chains of disease-associated mutations either contribute to the anionic
      patch, help create the second conserved surface, or point toward frataxin's
      hydrophobic core. These structural findings predict potential modes of protein
      protein and protein-iron binding.

PMID- 10900193
TI  - Intermolecular cross-linking between the periplasmic Loop3-4 regions of PomA, a
      component of the Na+-driven flagellar motor of Vibrio alginolyticus.
AB  - PomA and PomB form a complex that conducts sodium ions and generates the torque
      for the Na(+)-driven polar flagellar motor of Vibrio alginolyticus. PomA has four
      transmembrane segments. One periplasmic loop (loop(1-2)) connects segments 1 and
      2, and another (loop(3-4)), in which cysteine-scanning mutagenesis had been
      carried out, connects segments 3 and 4. When PomA with an introduced Cys residue
      (Cys-PomA) in the C-terminal periplasmic loop (loop(3-4)) was examined without
      exposure to a reducing reagent, a 43-kDa band was observed, whereas only a 25-kDa
      band, which corresponds to monomeric PomA, was observed under reducing
      conditions. The intensity of the 43-kDa band was enhanced in most mutants by the
      oxidizing reagent CuCl(2). The 43-kDa band was strongest in the P172C mutant. The
      motility of the P172C mutant was severely reduced, and P172C showed a dominant
      negative effect, whereas substitution of Pro with Ala, Ile, or Ser at this
      position did not affect motility. In the presence of DTT, the ability to swim was
      partially restored, and the amount of 43-kDa protein was reduced. These results
      suggest that the disulfide cross-link disturbs the function of PomA. When the
      mutated Cys residue was modified with N-ethylmaleimide, only the 25-kDa PomA band
      was labeled, demonstrating that the 43-kDa form is a cross-linked homodimer and
      suggesting that the loops(3-4) of adjacent subunits of PomA are close to each
      other in the assembled motor. We propose that this loop region is important for
      dimer formation and motor function.

PMID- 10900194
TI  - TIMP-3 binds to sulfated glycosaminoglycans of the extracellular matrix.
AB  - Of the four known tissue inhibitors of metalloproteinases (TIMPs), TIMP-3 is
      distinguished by its tighter binding to the extracellular matrix. The present
      results show that glycosaminoglycans such as heparin, heparan sulfate,
      chondroitin sulfates A, B, and C, and sulfated compounds such as suramin and
      pentosan efficiently extract TIMP-3 from the postpartum rat uterus. Enzymatic
      treatment by heparinase III or chondroitinase ABC also releases TIMP-3, but
      neither one alone gives complete release. Confocal microscopy shows
      colocalization of heparan sulfate and TIMP-3 in the endometrium subjacent to the
      lumen of the uterus. Immunostaining of TIMP-3 is lost upon digestion of tissue
      sections with heparinase III and chondroitinase ABC. The N-terminal domain of
      human TIMP-3 was expressed and found to bind to heparin with affinity similar to
      that of full-length mouse TIMP-3. The A and B beta-strands of the N-terminal
      domain of TIMP-3 contain two potential heparin-binding sequences rich in lysine
      and arginine; these strands should form a double track on the outer surface of
      TIMP-3. Synthetic peptides corresponding to segments of these two strands compete
      for heparin in the DNase II binding assay. TIMP-3 binding may be important for
      the cellular regulation of activity of the matrix metalloproteinases.

PMID- 10900195
TI  - Cdc42Hs and Rac1 GTPases induce the collapse of the vimentin intermediate
      filament network.
AB  - In this study we show that expression of active Cdc42Hs and Rac1 GTPases, two Rho
      family members, leads to the reorganization of the vimentin intermediate filament
      (IF) network, showing a perinuclear collapse. Cdc42Hs displays a stronger effect
      than Rac1 as 90% versus 75% of GTPase-expressing cells show vimentin collapse.
      Similar vimentin IF modifications were observed when endogenous Cdc42Hs was
      activated by bradykinin treatment, endogenous Rac1 by platelet-derived growth
      factor/epidermal growth factor, or both endogenous proteins upon expression of
      active RhoG. This reorganization of the vimentin IF network is not associated
      with any significant increase in soluble vimentin. Using effector loop mutants of
      Cdc42Hs and Rac1, we show that the vimentin collapse is mostly independent of
      CRIB (Cdc42Hs or Rac-interacting binding)-mediated pathways such as JNK or PAK
      activation but is associated with actin reorganization. This does not result from
      F-actin depolymerization, because cytochalasin D treatment or Scar-WA expression
      have merely no effect on vimentin organization. Finally, we show that genistein
      treatment of Cdc42 and Rac1-expressing cells strongly reduces vimentin collapse,
      whereas staurosporin, wortmannin, LY-294002, R(p)-cAMP, or RII, the regulatory
      subunit of protein kinase A, remain ineffective. Moreover, we detected an
      increase in cellular tyrosine phosphorylation content after Cdc42Hs and Rac1
      expression without modification of the vimentin phosphorylation status. These
      data indicate that Cdc42Hs and Rac1 GTPases control vimentin IF organization
      involving tyrosine phosphorylation events.

PMID- 10900197
TI  - Binding properties of agonists and antagonists to distinct allosteric states of
      the nicotinic acetylcholine receptor are incompatible with a concerted model.
AB  - Recent work has shown that the nicotinic acetylcholine receptor (nAChR) can be
      fixed in distinct conformations by chemical cross-linking with glutardialdehyde,
      which abolishes allosteric transitions in the protein. Here, two conformations
      that resemble the desensitized and the resting states were compared with respect
      to their affinities for different classes of ligands. The same ligands were
      tested for their ability to convert the nAChR from a conformation with low
      affinity to a conformation with high affinity for acetylcholine. As expected,
      agonists were found to bind with higher affinity to the desensitized state-like
      conformation and to induce a shift of the nAChR to this high affinity state. In
      contrast, although most antagonists tested bound preferentially to the
      desensitized receptor as well they failed to induce a change of the affinity for
      acetylcholine. These observations sharply contradict basic predictions of the
      concerted model, including the postulate of a preformed equilibrium between the
      different states of the nAChR in the absence of agonist. With a similar approach
      we could show that the non-competitive inhibitor ethidium is displaced in a non
      allosteric manner by other well characterized channel blockers from the cross
      linked nAChR. These results require revision of current models for the mechanisms
      underlying non-competitive antagonism at the nAChR.

PMID- 10900196
TI  - Single cell Ras-GTP analysis reveals altered Ras activity in a subpopulation of
      neurofibroma Schwann cells but not fibroblasts.
AB  - Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by
      multiple neurofibromas, peripheral nerve tumors containing mainly Schwann cells
      and fibroblasts. The NF1 gene encodes neurofibromin, a tumor suppressor
      postulated to function in part as a Ras GTPase-activating protein. The roles of
      different cell types and of elevated Ras-GTP in neurofibroma formation are
      unclear. To determine which neurofibroma cell type has altered Ras-GTP
      regulation, we developed an immunocytochemical assay for active, GTP-bound Ras.
      In NIH 3T3 cells, the assay detected overexpressed, constitutively activated K-,
      N-, and Ha-Ras and insulin-induced endogenous Ras-GTP. In dissociated
      neurofibroma cells from NF1 patients, Ras-GTP was elevated in Schwann cells but
      not fibroblasts. Twelve to 62% of tumor Schwann cells showed elevated Ras-GTP,
      unexpectedly revealing neurofibroma Schwann cell heterogeneity. Increased basal
      Ras-GTP did not correlate with increased cell proliferation. Normal human Schwann
      cells, however, did not demonstrate elevated basal Ras activity. Furthermore,
      compared with cells from wild type littermates, Ras-GTP was elevated in all mouse
      Nf1(-/-) Schwann cells but never in Nf1(-/-) mouse fibroblasts. Our results
      indicate that Ras activity is detectably increased in only some neurofibroma
      Schwann cells and suggest that neurofibromin is not an essential regulator of Ras
      activity in fibroblasts.

PMID- 10900198
TI  - Down-regulation of the PSI-F subunit of photosystem I (PSI) in Arabidopsis
      thaliana. The PSI-F subunit is essential for photoautotrophic growth and
      contributes to antenna function.
AB  - The PSI-F subunit of photosystem I is a transmembrane protein with a large
      lumenal domain. The role of PSI-F was investigated in Arabidopsis plants
      transformed with an antisense construct of the psaF cDNA. Several plant lines
      with reduced amounts of the PSI-F subunit were generated. Many of the transgenic
      plants died, apparently because they were unable to survive without the PSI-F
      subunit. Plants with 5% of PSI-F were capable of photoautotrophic growth but were
      much smaller than wild-type plants. The plants suffered severely under normal
      growth conditions but recovered somewhat in the dark indicating chronic
      photoinhibition. Photosystem I lacking PSI-F was less stable, and the stromal
      subunits PSI-C, PSI-D, and PSI-E were present in lower amounts than in wild type.
      The lack of PSI-F resulted in an inability of light-harvesting complex I-730 to
      transfer energy to the P700 reaction center. In thylakoids deficient in PSI-F,
      the steady state NADP(+) reduction rate was only 10% of the wild-type levels
      indicating a lower efficiency in oxidation of plastocyanin. Surprisingly, the
      lack of PSI-F also gave rise to disorganization of the thylakoids. The strict
      arrangement in grana and stroma lamellae was lost, and instead a network of
      elongated and distorted grana was observed.

PMID- 10900199
TI  - Versatile transcription of biphenyl catabolic bph operon in Pseudomonas
      pseudoalcaligenes KF707.
AB  - Pseudomonas pseudoalcaligenes KF707 possesses a chromosomally encoded bph gene
      cluster responsible for the catabolism of biphenyl/polychlorinated biphenyls. The
      gene cluster consists of (orf0)bphA1A2(orf3)bphA3A4BCX0X1X2X3D. We studied the
      role of orf0 and transcription in the KF707 bph operon. Primer extension analyses
      revealed that at least as many as six transcriptional initiation sites exist
      upstream of orf0, bphA1, bphX0, bphX1, and bphD, including two upstream of bphD.
      The orf0-disruptant failed to grow on biphenyl but accumulated large amounts of
      the biphenyl ring meta-cleavage yellow compound (2-hydroxy-6-oxo-6-phenylhexa-2,
      4-dienoate). Western blot analysis revealed that ORF0 protein is inducibly
      expressed in KF707 in the presence of biphenyl. Gel shift assay revealed that
      ORF0 directly binds to the orf0 operator region. This binding was greatly
      enhanced by addition of the biphenyl ring meta-cleavage yellow compound. These
      results indicated that orf0, bphA1A2(orf3)bphA3A4BC and bphX0X1X2X3D are
      independently transcribed, and that ORF0 protein belonging to the GntR family is
      involved in the regulation of the bph operon in KF707 and is absolutely required
      for the expression of orf0 and bphX0X1X2X3D.

PMID- 10900200
TI  - A primitive ATP receptor from the little skate Raja erinacea.
AB  - P2Y ATP receptors are widely expressed in mammalian tissues and regulate a broad
      range of activities. Multiple subtypes of P2Y receptors have been identified and
      are distinguished both on a molecular basis and by pharmacologic substrate
      preference. Functional evidence suggests that hepatocytes from the little skate
      Raja erinacea express a primitive P2Y ATP receptor lacking pharmacologic
      selectivity, so we cloned and characterized this receptor. Skate hepatocyte cDNA
      was amplified with degenerate oligonucleotide probes designed to identify known
      P2Y subtypes. A single polymerase chain reaction product was found and used to
      screen a skate liver cDNA library. A 2314-base pair cDNA clone was generated that
      contained a 1074-base pair open reading frame encoding a 357-amino acid gene
      product with 61-64% similarity to P2Y(1) receptors and 21-37% similarity to other
      P2Y receptor subtypes. Pharmacology of the putative P2Y receptor was examined
      using the Xenopus oocyte expression system and revealed activation by a range of
      nucleotides. The receptor was expressed widely in skate tissue and was expressed
      to a similar extent in other primitive organisms. Phylogenetic analysis suggested
      that this receptor is closely related to a common ancestor of the P2Y subtypes
      found in mammals, avians, and amphibians. Thus, the skate liver P2Y receptor
      functions as a primitive P2Y ATP receptor with broad pharmacologic selectivity
      and is related to the evolutionary forerunner of P2Y(1) receptors of higher
      organisms. This novel receptor should provide an effective comparative model for
      P2Y receptor pharmacology and may improve our understanding of nucleotide
      specificity among the family of P2Y ATP receptors.

PMID- 10900201
TI  - Isolation and characterization of a novel conus peptide with apparent
      antinociceptive activity.
AB  - Cone snails are tropical marine mollusks that envenomate prey with a complex
      mixture of neuropharmacologically active compounds. We report the discovery and
      biochemical characterization of a structurally unique peptide isolated from the
      venom of Conus marmoreus. The new peptide, mr10a, potently increased withdrawal
      latency in a hot plate assay (a test of analgesia) at intrathecal doses that do
      not produce motor impairment as measured by rotarod test. The sequence of mr10a
      is NGVCCGYKLCHOC, where O is 4-trans-hydroxyproline. This sequence is highly
      divergent from all other known conotoxins. Analysis of a cDNA clone encoding the
      toxin, however, indicates that it is a member of the recently described T
      superfamily. Total chemical synthesis of the three possible disulfide
      arrangements of mr10a was achieved, and elution studies indicate that the native
      form has a disulfide connectivity of Cys1-Cys4 and Cys2-Cys3. This disulfide
      linkage is unprecedented among conotoxins and defines a new family of Conus
      peptides.

PMID- 10900202
TI  - Cloning and characterization of a Saccharomyces cerevisiae alkaline ceramidase
      with specificity for dihydroceramide.
AB  - In a previous study, we reported that the Saccharomyces cerevisiae gene YPC1
      encodes an alkaline ceramidase with a dual activity, catalyzing both hydrolysis
      and synthesis of yeast ceramide (Mao, C., Xu, R., Bielawska, A., and Obeid, L. M.
      (2000) J. Biol. Chem. 275, 6876-6884). In this study, we have identified a YPC1
      homologue in S. cerevisiae that also encodes an alkaline ceramidase. We show that
      these two ceramidases have different substrate specificity, such that YPC1p
      preferentially hydrolyzes phytoceramide, whereas the new ceramidase YDC1p
      hydrolyzes dihydroceramide preferentially and phytoceramide only slightly.
      Neither enzyme hydrolyzes unsaturated mammalian-type ceramide. In contrast to
      YPC1p, YDC1p had only minor in vitro reverse activity of catalyzing
      dihydroceramide formation from a free fatty acid and dihydrosphingosine and no
      activity with phytosphingosine. Overexpression of YDC1p had no reverse activity
      in non-stressed yeast cells, but like YPC1p suppressed the inhibition of growth
      by fumonisin B1 albeit more modestly. Deletion of YDC1 and YPC1 or both did not
      apparently affect growth, suggesting neither gene is essential. However, the
      Deltaydc1 deletion mutant but not the Deltaypc1 deletion mutant was sensitive to
      heat stress, indicating a role for dihydroceramide but not phytoceramide in heat
      stress responses, and suggesting that the two enzymes have distinct physiological
      functions.

PMID- 10900203
TI  - p135 src homology 2 domain-containing inositol 5'-phosphatase (SHIPbeta ) isoform
      can substitute for p145 SHIP in fcgamma RIIB1-mediated inhibitory signaling in B
      cells.
AB  - The inositol 5'-phosphatase, SHIP (also referred to as SHIP-1 or SHIPalpha), is
      expressed in all cells of the hematopoietic lineage. Depending on the cell type
      being investigated and the state of differentiation, SHIP isoforms of several
      different molecular masses (170, 160, 145, 135, 125, and 110 kDa) have been seen
      in immunoblots. However, the function of the individual isoforms and the effect
      of expressing multiple isoforms simultaneously are not understood. Some of these
      SHIP isoforms have recently been characterized at the level of primary sequence.
      In this report, we investigated the function of the recently characterized 135
      kDa SHIP isoform (SHIPbeta), which appears to possess the catalytic domain but
      lacks some of the protein-protein interaction motifs at the C terminus. By
      reconstituting SHIP-deficient DT40 B cells with either SHIPbeta or the better
      characterized p145 SHIPalpha, we addressed the function of SHIPbeta in the
      complete absence of SHIPalpha. We observed that SHIPbeta had enzymatic activity
      comparable with SHIPalpha and that SHIPbeta was able to reconstitute
      F(c)gammaRIIB1-mediated inhibition of B cell receptor-induced signaling events
      such as calcium flux and Akt and mitogen-activated protein kinase activation.
      SHIPbeta was readily phosphorylated in response to B cell receptor cross-linking
      with the inhibitory receptor F(c)gammaRIIB1 and SHIPbeta also interacted with the
      adapter protein Shc. During these studies we also observed that the SHIPalpha or
      SHIPbeta interaction with Grb2 is not required for F(c)gammaRIIB1-mediated
      inhibition of calcium flux. These data suggest that SHIPbeta, which is normally
      expressed in B cells along with SHIPalpha, functions comparably with SHIPalpha
      and that these two isoforms are not likely to be antagonistic in their function
      in vivo.

PMID- 10900204
TI  - Functions of a rho-specific guanine nucleotide exchange factor in neurite
      retraction. Possible role of a proline-rich motif of KIAA0380 in localization.
AB  - The Rho/Rho kinase signaling pathway plays an essential role in neurite
      retraction and cell rounding in response to G(12/13)-coupled receptor activation
      in neuronal cells. The Rho guanine nucleotide exchange factor involved in these
      processes has not been identified. To monitor the activation state of Rho kinase,
      we developed a vimentin head/Rho kinase chimera, which is intramolecularly
      phosphorylated in a Rho-dependent manner at Ser(71) of the fused vimentin head.
      Using this system, we identified a clone termed KIAA0380, which contains the G
      alpha(12/13)-binding domain as well as a tandem of the Dbl homology/pleckstrin
      homology (DH/PH) domain, as an activator of Rho/Rho kinase signaling. Molecular
      dissection analyses revealed that a proline-rich motif C-terminally adjacent to
      DH/PH domain is essential for plasma membrane localization of KIAA0380 and
      cortical actin reorganization followed by cell rounding. In contrast, the DH/PH
      domain of KIAA0380 is localized in the cytoplasm, where it activates Rho/Rho
      kinase and induces stress fiber formation, consistent with results using p115 Rho
      guanine nucleotide exchange factor, which has a similar structure to KIAA0380 but
      lacks a proline-rich motif. These results suggest that upon stimulation, KIAA0380
      translocates to the plasma membrane via the proline-rich motif and there
      activates Rho/Rho kinase signaling. In neuroblastoma Neuro2a cells, KIAA0380 was
      observed in the tips of neurites, a location where cortical actin reorganization
      is induced upon stimulation with lysophosphatidic acid. Ectopic expression of the
      N-terminal fragment inhibited lysophosphatidic acid-induced neurite retraction of
      Neuro2a cells. These results suggest that KIAA0380 plays an important role in
      neurite retraction through Rho-dependent signaling.

PMID- 10900205
TI  - Thrombospondin type 1 repeats interact with matrix metalloproteinase 2.
      Regulation of metalloproteinase activity.
AB  - Thrombospondins are thought to function as inhibitors of angiogenesis. However,
      the mechanism(s) of this activity is not well understood. In this study, we have
      used the yeast two-hybrid system to identify proteins that interact with the
      thrombospondins 1 (TSP1) and 2 (TSP2) properdin-like type 1 repeats (TSR). One of
      the proteins identified that interacted with both TSR was matrix
      metalloproteinase 2 (MMP2). The isolated MMP2 cDNA clone encoded amino acid
      residues 237-633, which include the fibronectin-like gelatin binding region
      flanking the catalytic center and the carboxyl hemopexin-like region. Further
      testing of this clone demonstrated that the TSR interacted with the NH(2)
      terminal region of the MMP2 that contains the catalytic domain. The protein
      interaction observed in yeast was further demonstrated by immunoprecipitation and
      Western blotting using purified intact TSP1, TSP2, MMP2, and MMP9. Although MMP2
      interacted with TSP1 and TSP2 via its gelatin-binding domain or a closely mapping
      site, neither TSP1 nor TSP2 was degraded by MMP2 in vitro. Tissue culture and in
      vitro assays demonstrated that the presence of purified TSR and intact TSP1
      resulted in inhibition of MMP activity. The ability of TSP1 to inhibit MMP3
      dependent activation of pro-MMP9 and thrombin-induced activation of pro-MMP2
      suggests that the TSPs may inhibit MMP activity by preventing activation of the
      MMP2 and MMP9 zymogens.

PMID- 10900206
TI  - Participation of transcription elongation factor XSII-K1 in mesoderm-derived
      tissue development in Xenopus laevis.
AB  - We isolated a cDNA clone for a novel member of the S-II family of transcription
      elongation factors from Xenopus laevis. This S-II, named XSII-K1, is assumed to
      be the Xenopus homologue of mouse SII-K1 that we reported previously (Taira, Y.,
      Kubo, T., and Natori, S. (1998) Genes Cells 3, 289-296). Expression of the XSII
      K1 gene was found to be restricted to mesoderm-derived tissues such as liver,
      kidney, and skeletal muscle. Contrary to the general S-II gene, expression of the
      XSII-K1 gene was not detected in embryos at stages earlier than 11. The animal
      cap assay revealed that activin A, but not basic fibroblast growth factor,
      induced expression of the XSII-K1 gene and that it participated in the expression
      of mesoderm-specific genes such as Xbra and Xalpha-actin. This is the first
      demonstration that the regulation at the level of transcription elongation is
      included in the development of mesoderm-derived tissues.

PMID- 10900209
TI  - A switch mechanism for G beta gamma activation of I(KACh).
AB  - G protein-gated inwardly rectifying potassium (GIRK) channels are a family of
      K(+)-selective ion channels that slow the firing rate of neurons and cardiac
      myocytes. GIRK channels are directly bound and activated by the G protein G beta
      gamma subunit. As heterotetramers, they comprise the GIRK1 and the GIRK2, -3, or 
      4 subunits. Here we show that GIRK1 but not the GIRK4 subunit is phosphorylated
      when heterologously expressed. We found also that phosphatase PP2A
      dephosphorylation of a protein in the excised patch abrogates channel activation
      by G beta gamma. Experiments with the truncated molecule demonstrated that the
      GIRK1 C-terminal is critical for both channel phosphorylation and channel
      regulation by protein phosphorylation, but the critical phosphorylation sites
      were not located on the C terminus. These data provide evidence for a novel
      switch mechanism in which protein phosphorylation enables G beta gamma gating of
      the channel complex.

PMID- 10900208
TI  - Identification of mammalian TOM22 as a subunit of the preprotein translocase of
      the mitochondrial outer membrane.
AB  - A mitochondrial outer membrane protein of approximately 22 kDa (1C9-2) was
      purified from Vero cells assessing immunoreactivity with a monoclonal antibody,
      and the cDNA was cloned based on the partial amino acid sequence of the trypsin
      digested fragments. 1C9-2 had 19-20% sequence identity to fungal Tom22, a
      component of the preprotein translocase of the outer membrane (the TOM complex)
      with receptor and organizer functions. Despite such a low sequence identity, both
      shared a remarkable structural similarity in the hydrophobicity profile, membrane
      topology in the Ncyt-Cin orientation through a transmembrane domain in the middle
      of the molecule, and the abundant acidic amino acid residues in the N-terminal
      domain. The antibodies against 1C9-2 inhibited the import of a matrix-targeted
      preprotein into isolated mitochondria. Blue native polyacrylamide gel
      electrophoresis of digitonin-solubilized outer membranes revealed that 1C9-2 is
      firmly associated with TOM40 in the approximately 400-kDa complex, with a size
      and composition similar to those of the fungal TOM core complex. Furthermore, 1C9
      2 complemented the defects of growth and mitochondrial protein import in
      Deltatom22 yeast cells. Taken together, these results demonstrate that 1C9-2 is a
      functional homologue of fungal Tom22 and functions as a component of the TOM
      complex.

PMID- 10900210
TI  - Mechanism of autoregulation by an archaeal transcriptional repressor.
AB  - The basal transcription machinery of archaea corresponds to the core components
      of the eucaryal RNA polymerase II apparatus. Thus, archaea possess a complex
      multi-subunit RNA polymerase, a TATA box-binding protein and a protein termed
      transcription factor B (TFB), which is a homologue of eucaryal transcription
      factor IIB (TFIIB). Intriguingly, archaeal genome sequencing projects have
      revealed the existence of homologues of bacterial transcriptional regulators. To
      investigate the mechanism of transcriptional regulation in archaea we have
      studied one such molecule, Lrs14, a Sulfolobus solfataricus P2 homologue of the
      bacterial leucine-responsive regulatory protein, Lrp. We find that purified Lrs14
      specifically represses the transcription of its own gene in a reconstituted in
      vitro transcription system. Furthermore, we show that Lrs14 binding sites overlap
      the basal promoter elements of the Lrs14 promoter and reveal that binding of
      Lrs14 to these sites prevents promoter recognition by TATA box-binding protein
      and TFB.

PMID- 10900211
TI  - A family of highly conserved glycosomal 2-hydroxyacid dehydrogenases from
      Phytomonas sp.
AB  - Phytomonas sp. contains two malate dehydrogenase isoforms, a mitochondrial
      isoenzyme with a high specificity for oxaloacetate and a glycosomal isozyme that
      acts on a broad range of substrates (Uttaro, A. D., and Opperdoes, F.R. (1997)
      Mol. Biochem. Parasitol. 89, 51-59). Here, we show that the low specificity of
      the latter isoenzyme is the result of a number of recent gene duplications that
      gave rise to a family of glycosomal 2-hydroxyacid dehydrogenase genes. Two of
      these genes were cloned, sequenced, and overexpressed in Escherichia coli.
      Although both gene products have 322 amino acids, share 90.4% identical residues,
      and have a similar hydrophobicity profile and net charge, their kinetic
      properties were strikingly different. One isoform behaved as a real malate
      dehydrogenase with a high specificity for oxaloacetate, whereas the other showed
      no activity with oxaloacetate but was able to reduce other oxoacids, such as
      phenyl pyruvate, 2-oxoisocaproate, 2-oxovalerate, 2-oxobutyrate, 2-oxo-4
      methiolbutyrate, and pyruvate.

PMID- 10900212
TI  - Stoichiometry and compartmentation in G protein-coupled receptor signaling:
      implications for therapeutic interventions involving G(s).
AB  - There is great therapeutic interest in manipulating (either enhancing or
      suppressing) G protein-coupled receptor (GPCR) signal transduction. However, most
      current strategies are limited to pharmacological activation or blockade of
      receptors. Human gene therapy, including both overexpression and antisense
      approaches, may allow manipulation of GPCR signaling at steps distal to
      receptors. To fully understand the impact of such therapy, the transduction of
      signals between the multiple components of GPCR signaling and their interaction
      with other cellular molecules must be understood in the context of both normal
      physiology and disease. Defining the stoichiometric relationship among multiple
      components of GPCR signaling is a first step. We summarize data showing the
      substantial excess of G(alphas) relative to both beta-adrenergic receptors and
      adenylyl cyclase. A predominant idea regarding signaling via GPCRs has for over
      20 years emphasized the concept of random movement and collision ("collision
      coupling") of proteins within the lipid bilayer of the plasma membrane. This
      notion does not readily account for the rapidity and fidelity of signal
      transduction by the multiple components involved in GPCR-G protein-effector
      systems, especially considering the low abundance of these proteins in cells.
      Recently, many components involved in signal transduction by GPCRs have been
      shown to exist primarily in microdomains of the plasma membrane, in particular,
      caveolae. These and other structures may serve to compartmentalize signals,
      thereby optimizing signal transduction between an agonist and specific effectors.
      The formation, organization, and maintenance of such structures may prove to be
      altered in disease states associated with disregulated signaling. In addition, we
      speculate that identification of genetic polymorphisms of and therapy targeted to
      components that are critical for determining efficacy (e.g., effectors such as
      adenylyl cyclase) will provide important future therapeutic strategies.

PMID- 10900213
TI  - Placental transporters relevant to drug distribution across the maternal-fetal
      interface.

PMID- 10900215
TI  - [Nphe(1)]NC(1-13)NH(2) selectively antagonizes nociceptin/orphanin FQ-stimulated
      G-protein activation in rat brain.
AB  - [Phe(1)psi(CH(2)-NH)Gly(2)]noc/OFQ(1-13)-amide ([F/G]NC(1-13)NH(2)) and acetyl
      RYYRIK-amide (Ac-RYYRIK-NH(2)), two peptidic ligands of the nociceptin/orphanin
      FQ (noc/OFQ) receptor, have been shown to exert both agonist and antagonist
      activity in different in vitro and in vivo systems. This is despite the
      observation that both peptides competitively antagonized the coupling of the
      activated receptor to G-proteins in brain preparations, measured in GTPgamma(35)S
      binding assays. In this study, [Nphe(1)]NC(1-13)-amide ([Nphe(1)]NC(1-13)NH(2)),
      a new noc/OFQ analog recently characterized as a pure and selective noc/OFQ
      receptor antagonist in several in vitro and in vivo assay systems, was shown to
      competitively inhibit the noc/OFQ-stimulated GTPgamma(35)S binding to rat
      cerebral cortex membranes with pA(2) of 7.76 (Schild analysis). This antagonism
      of noc/OFQ receptor G-protein coupling was selective because the peptide
      inhibited the noc/OFQ-evoked GTPgamma(35)S binding to rat brain membranes but not
      that evoked by selective agonists of the mu-, delta-, and kappa-opioid receptors.
      In rat cortical membranes, the effects of [F/G]NC(1-13)NH(2) and Ac-RYYRIK-NH(2)
      on the binding of GTPgamma(35)S were clearly differentiated from the effect of
      [Nphe(1)]NC(1-13)NH(2) when the concentration of GDP, competing with GTPgammaS
      for binding, was lowered from 100 microM (assay optimum) to 5 microM. At 5 microM
      GDP, the former peptides showed clear partial agonist activity, whereas
      [Nphe(1)]NC(1-13)NH(2) did not. These data indicate that only [Nphe(1)]NC(1
      13)NH(2) was a pure antagonist of noc/OFQ receptor G-protein coupling.
      Furthermore, it is suggested that the variable behavior of [F/G]NC(1-13)NH(2) and
      Ac-RYYRIK-NH(2) (agonist, partial agonist, and antagonist) in different in vitro
      and in vivo systems may be explained by different partial GTP binding agonism and
      the existence of a GTP binding stimulus/response reserve (coupling reserve).

PMID- 10900214
TI  - Cytochalasin E, an epoxide containing Aspergillus-derived fungal metabolite,
      inhibits angiogenesis and tumor growth.
AB  - Several previously identified inhibitors of angiogenesis have been epoxide
      containing fungus-derived metabolites. We therefore hypothesized that novel
      epoxide-containing low molecular weight compounds structurally resembling known
      antiangiogenic agents may also exhibit antiangiogenic activity. Cytochalasin E
      was found to be a potent and selective inhibitor of bovine capillary endothelial
      (BCE) cell proliferation. Cytochalasin E differed from other cytochalasins by the
      presence of an epoxide. The epoxide was required for activity, because acid
      catalyzed hydrolysis of the epoxide abrogated the specificity and potency of
      cytochalasin E. Phalloidin staining indicated that disruption of actin stress
      fibers by cytochalasin E occurred only at relatively high concentrations. Lower
      concentrations of cytochalasin E preferentially inhibited BCE cell proliferation
      without disrupting actin stress fibers. In vivo, cytochalasin E inhibited
      angiogenesis induced by basic fibroblast growth factor by 40% to 50% in the mouse
      cornea assay and inhibited the growth of Lewis lung tumors by approximately 72%.
      Cytochalasin E is a potent antiangiogenic agent that may hold promise for the
      treatment of cancer and other types of pathologic angiogenesis.

PMID- 10900216
TI  - Quantitative imaging in live human cells reveals intracellular alpha(1)
      adrenoceptor ligand-binding sites.
AB  - Cellular distribution and binding characteristics of native alpha(1)
      adrenoceptors (ARs) were determined in a live, single, human smooth muscle cell
      (SMC) with confocal laser scanning microscopy and a fluorescent ligand, BODIPY-FL
      prazosin (QAPB). This allowed single-cell competitive ligand binding and showed
      that 40% of alpha(1)-AR-binding sites in native cells are intracellular. QAPB had
      high affinity and acted as a nonselective, competitive antagonist versus
      [(3)H]prazosin at cloned human alpha(1a)-, alpha(1b)-, and alpha(1d)-AR subtypes
      on membrane preparations and whole cells. RS100329 had 70-fold selectivity for
      alpha(1a)-ARs versus alpha(1b)- and alpha(1d)-ARs, validating its use to identify
      this subtype. In similar cells QAPB-associated fluorescence provided quantitative
      data analogous and comparable to [(3)H]prazosin binding in whole cells. In human,
      dissociated, prostatic smooth muscle cells QAPB-associated fluorescence binding
      exhibited specific high-affinity binding properties (FK(D) = 0.63 +/- 0.02 nM),
      which was 3- to 4-fold higher compared with recombinant cells (FK(D) = 2. 1-2.3
      nM). Internal consistency in the data showed that affinity is greater, in
      general, in membrane preparations than in cells but also greater in the native
      prostatic tissues or cells than in equivalent recombinant receptors. Fluorescence
      revealed binding sites both on the plasmalemmal membrane and on intracellular
      compartments: at all locations RS100329 inhibited QAPB binding identifying the
      sites as alpha(1A)-ARs. Quantitative three-dimensional mapping of QAPB-associated
      fluorescence binding in native human cells showed that 40% of high-affinity
      binding sites was in intracellular compartments. This provides a potential new
      site for physiological agonism and makes intracellular access a potential
      differentiator of drug action.

PMID- 10900217
TI  - Evaluation of selective NK(1) receptor antagonist CI-1021 in animal models of
      inflammatory and neuropathic pain.
AB  - CI-1021 ([(2-benzofuran)-CH(2)OCO]-(R)-alpha-MeTrp-(S)-NHCH(CH (3))Ph) is a
      selective and competitive neurokinin-1 (NK(1)) receptor antagonist. This study
      examines its activity in animal models of inflammatory and neuropathic pain. In
      mice, CI-1021 (1-30 mg/kg, s.c.) dose dependently blocked the development of the
      late phase of the formalin response with a minimum effective dose (MED) of 3
      mg/kg. Two chemically unrelated NK(1) receptor antagonists, CP-99,994 (3-30
      mg/kg) and SR 140333 (1-100 mg/kg), also dose dependently blocked the late phase,
      with respective MEDs of 3 and 10 mg/kg. PD 156982, a NK(1) receptor antagonist
      with poor central nervous system penetration, failed to have any effect. However,
      when administered i. c.v., it selectively blocked the late phase of the formalin
      response. Chronic constrictive injury (CCI) to a sciatic nerve in the rat induced
      spontaneous pain, thermal and mechanical hyperalgesia, and cold, dynamic, and
      static allodynia. CI-1021 (10-100 mg/kg) and morphine (3 mg/kg) blocked all the
      responses except dynamic allodynia. Carbamazepine (100 mg/kg) was weakly
      effective against all the responses. Once daily administration of morphine (3
      mg/kg, s. c.) in CCI rats led to the development of tolerance within 6 days.
      Similar administration of CI-1021 (100 mg/kg, s.c.) for up to 10 days did not
      induce tolerance. Moreover, the morphine tolerance failed to cross-generalize to
      CI-1021. CI-1021 blocked the CCI-induced hypersensitivity in the guinea pig, with
      a MED of 0.1 mg/kg, p.o. CI-1021 (10-100 mg/kg, s.c.) did not show
      sedative/ataxic action in the rat rota-rod test. It is suggested that NK(1)
      receptor antagonists possess a superior side effect profile to carbamazepine and
      morphine and may have a therapeutic use for the treatment of inflammatory and
      neuropathic pain.

PMID- 10900218
TI  - Opioid-induced cardioprotection against myocardial infarction and arrhythmias:
      mitochondrial versus sarcolemmal ATP-sensitive potassium channels.
AB  - We examined the role of the sarcolemmal and mitochondrial ATP-sensitive potassium
      (K(ATP)) channel in a rat model of myocardial infarction after stimulation with
      the selective delta(1)-opioid receptor agonist TAN-67. Hearts were subjected to
      30 min of regional ischemia and 2 h of reperfusion. Infarct size was expressed as
      a percentage of the area at risk. TAN-67 significantly reduced infarct size/area
      at risk (29.6 +/- 3.3) versus control (63. 1 +/- 2.3). The sarcolemmal-selective
      K(ATP) channel antagonist HMR 1098, administered 10 min before TAN-67, did not
      significantly attenuate cardioprotection (26.0 +/- 7.3) at a dose (3 mg/kg) that
      had no effect in the absence of TAN-67 (56.3 +/- 4.3). Pretreatment with the
      mitochondrial selective antagonist 5-hydroxydecanoic acid (5-HD) 5 min before the
      30-min occlusion completely abolished TAN-67-induced cardioprotection (54.3 +/-
      2.7), but had no effect in the absence of TAN-67 (62.6 +/- 4.1), suggesting the
      involvement of the mitochondrial K(ATP) channel. Additionally, we examined the
      antiarrhythmic effects of TAN-67 in the presence or absence of 5-HD and HMR 1098
      during 30 min of ischemia. Control animals had an average arrhythmia score of
      10.40 +/- 2.41. TAN-67 significantly reduced the arrhythmia score during 30 min
      of ischemia (2.38 +/- 0. 85). 5-HD and HMR 1098 in the absence of TAN-67 produced
      an insignificant decrease in the arrhythmia score (8.80 +/- 2.56 and 4. 20 +/-
      1.07, respectively). 5-HD administration before TAN-67 treatment abolished its
      antiarrhythmic effect (4.71 +/- 1.11). However, HMR 1098 did not abolish TAN-67
      induced protection against arrhythmias (1.67 +/- 0.80). These data suggest that
      delta(1)-opioid receptor stimulation is cardioprotective against myocardial
      ischemia and sublethal arrhythmias and suggest a role for the mitochondrial
      K(ATP) channel in mediating these cardioprotective effects.

PMID- 10900219
TI  - Systemic nicotine stimulates dopamine release in nucleus accumbens: re-evaluation
      of the role of N-methyl-D-aspartate receptors in the ventral tegmental area.
AB  - Systemic nicotine stimulates dopamine (DA) release in the nucleus accumbens
      (NAcc), and N-methyl-D-aspartate (NMDA) receptors in the ventral tegmental area
      (VTA) appear to be involved. However, it is not known whether the secretion of DA
      elicited by nicotine depends on the tonic and/or phasic activation of NMDA
      receptors by glutamate (Glu). To clarify this, in vivo microdialysis was
      conducted in freely moving, alert rats to measure DA and Glu overflows in the
      NAcc and Glu in the VTA. Nicotine (0.065, 0.09, or 0.135 mg/kg delivered i.v. at
      0.09 mg/kg/60 s via a jugular cannula) dose dependently stimulated NAcc DA
      secretion (P <.05). However, 0.065 mg/kg nicotine failed to stimulate Glu release
      in the VTA, whereas higher doses of nicotine (> or =0.09 mg/kg) were effective (P
      <.05). Administering the competitive NMDA receptor antagonists, 2-amino-5
      phosphonopentanoic acid (AP-5; 1 mM) or 0.2 mM cis-4-phosphonomethyl-2-piperidine
      carboxylic acid (CGS 19755) through the VTA probe, abolished NAcc DA release
      after 0.065 mg/kg nicotine (P <.01) and reduced the response to 0.09 mg/kg
      nicotine. Therefore, the NAcc DA response to a relatively low dose of nicotine
      depends on the tonic activation of NMDA receptors in the VTA. In contrast,
      infusing 1 mM 2-amino-5-phosphonopentanoic acid or 1 mM 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), an alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate (AMPA) receptor antagonist, into the NAcc through the microdialysis
      probe had no effect on NAcc DA secretion in response to 0.09 mg/kg nicotine.
      These findings, coupled with data showing that Glu secretion in the VTA was
      stimulated only by higher doses of nicotine, indicate that the phasic release of
      VTA Glu is involved in the NAcc DA response to higher doses of nicotine (> or
      =0.09 mg/kg).

PMID- 10900220
TI  - alpha(2)-adrenergic receptors stimulate oligopeptide transport in a human
      intestinal cell line.
AB  - Di- and tripeptides, as well as peptidomimetic drugs such as cephalexin (CFX),
      are absorbed by enterocytes via the oligopeptide transporter PepT1. We recently
      showed that the alpha(2)-adrenergic agonist clonidine increases CFX absorption in
      anaesthetized rats. Herein, we investigated whether alpha(2)-adrenergic receptors
      can directly affect PepT1 activity in a clone of the differentiated human
      intestinal cell line Caco-2 (Caco-2 3B) engineered to stably express alpha(2A)
      adrenergic receptors at a density similar to that found in normal mucosa.
      Measurement of CFX fluxes across cell monolayers cultured on transwell filters
      demonstrated that the alpha(2)-agonists clonidine and UK14304 caused a 2-fold
      increase of CFX transport in Caco-2 3B cells, but not in Caco-2 (expressing PepT1
      but not alpha(2)-adrenergic receptors) or in the HT29 19A clone (expressing
      alpha(2)-adrenergic receptors but not PepT1). The stimulatory effect of clonidine
      was abolished by glycyl-sarcosine (a competitor for the transporter) and blocked
      by yohimbine or RX821002 (alpha(2)-antagonists). Analysis of the kinetics of CFX
      transport in control and clonidine-treated Caco-2 3B cells showed that clonidine
      increased V(max) of CFX transport without changing K(m). Clonidine action was
      abolished by colchicine but not altered by amiloride, demonstrating that
      microtubule integrity but not Na(+)/H(+) exchanger activity is necessary for the
      effect of alpha(2)-agonists to occur. In conclusion, clonidine can directly
      activate alpha(2)-adrenergic receptors located on epithelial cells. The precise
      molecular mechanisms whereby these receptors modulate PepT1 activity remain to be
      elucidated but an increased translocation to the apical membrane of preformed
      cytoplasmic transporter molecules is likely to be involved.

PMID- 10900221
TI  - Potentiation of thioacetamide liver injury in diabetic rats is due to induced
      CYP2E1.
AB  - Thioacetamide (TA)-induced hepatotoxicity is potentiated in streptozotocin (STZ)
      induced diabetic rats. The relative roles of CYP2E1 and FMO1 in the mechanism of
      TA-associated liver injury were investigated. In the STZ-induced diabetic rat,
      hepatic CYP2E1 protein concentration and p-nitrophenol hydroxylation were induced
      8- and 5.6-fold, respectively. Pretreatment with the CYP2E1 inducer, isoniazid
      (INH, 250 mg/kg, i.p.) before TA (300 mg/kg, i.p.) administration significantly
      increased TA-associated liver injury as assessed by plasma alanine
      aminotransferase (ALT). Hepatic CYP2E1 expression and p-nitrophenol hydroxylation
      were induced 2.2- and 2. 5-fold in the INH-pretreated rat, respectively.
      Inhibition of CYP2E1 by diallyl sulfide (DAS, 200 mg/kg, p.o., two doses) before
      TA administration, decreased plasma ALT activity by 60% in the nondiabetic rat
      and by 75% in the diabetic rat. Abolition of microsomal p-nitrophenol
      hydroxylation and CCl(4)-induced liver injury confirmed that hepatic CYP2E1 was
      highly inhibited by DAS. Hepatic flavin-containing monooxygenase (FMO) form 1
      expression and methimazole-dependent oxidation of thiocholine were induced 2.5-
      and 1.8-fold in the diabetic rat, respectively. Dietary administration of 0.25%
      indole-3-carbinol (I3C) for 10 days inhibited FMO1 expression and enzyme activity
      in both nondiabetic and diabetic rats. Paradoxically, TA-induced liver injury was
      increased in these I3C-pretreated rats. These findings indicate that hepatic
      CYP2E1 appears to be primarily involved in bioactivation of TA. In the STZ
      induced diabetic rat, diabetes-induced CYP2E1 appears to be responsible for the
      potentiated liver injury; Even though hepatic FMO1 is induced in the diabetic
      rat, it is unlikely to mediate the potentiated TA hepatotoxicity.

PMID- 10900222
TI  - The influence of coordinate overexpression of glutathione phase II detoxification
      gene products on drug resistance.
AB  - Glutathione (GSH), glutathione S-transferases (GSTs), and the multidrug
      resistance-associated protein 1 (MRP1) have been independently studied for their
      contributions to drug resistance. Single cDNA transfection experiments have
      provided inconsistent and disparate conclusions with respect to the importance of
      GSH and GST in conferring a resistant phenotype. Because these three proteins can
      act as a concerted coordinated pathway, we reasoned that equivalent increases may
      be required for enhanced resistance to be expressed. We have assembled these
      proteins together, or in various combinations, to determine whether they show
      cooperativity in determining drug response. Increased expression through single
      cDNA transfection of GSTpi, gamma-glutamylcysteine synthetase (gamma-GCS)
      (regulatory plus catalytic subunits), or MRP1 enhanced resistance to a number of
      anticancer drugs. Cotransfection of GSTpi and GCS, gave higher resistance to
      doxorubicin, etoposide, and vincristine than with either alone. Resistance toward
      chlorambucil and ethacrynic acid was similar in cells overexpressing either
      component or overexpressing GST alone. Coexpression of GSTpi with MRP1 conferred
      significant resistance above that seen for MRP1 alone to chlorambucil, etoposide,
      ethacrynic acid, and vincristine. The combination of GCS and MRP1 did not afford
      additional resistance above MRP1 alone. When all three were transfected,
      significantly higher levels of resistance were found for doxorubicin and
      etoposide. These results support the concept that coordinate enhancement of focal
      thiol elements of detoxification pathways provides a more efficient protective
      phenotype than do single components alone.

PMID- 10900223
TI  - Basis for dosing time-dependent changes in the antiviral activity of interferon
      alpha in mice.
AB  - The influence of dosing time on the pharmacological effect (antiviral activity)
      of interferon-alpha (IFN-alpha), and the pharmacological and pharmacokinetic
      mechanisms, were investigated in ICR male mice under a 12-h light/dark cycle
      (lights on from 7:00 AM to 7:00 PM). 2'-5'Oligoadenylate synthetase activity in
      plasma at 24 h after IFN-alpha (10 MI.U./kg, i.v.) injection, as an index of
      antiviral activity, was significantly higher for injections given at 9:00 AM than
      for injections given at 9:00 PM (P <.05). The uptake of [(3)H]thymidine by
      lymphocytes after 24-h incubation with IFN-alpha, as an index of lymphocyte
      stimulating effect, was significantly higher in cells obtained at 9:00 AM than in
      the cells obtained at 9:00 PM (P <.01). The number of receptors per cell and the
      expression of interferon-stimulated gene factor in lymphocytes after 24-h
      incubation with IFN-alpha were significantly higher in the cells obtained at 9:00
      AM than at 9:00 PM (P <.05). A significant dosing time-dependent difference was
      demonstrated for the pharmacokinetic parameters of IFN-alpha, which showed higher
      clearance for injections given at 9:00 PM than for those at 9:00 AM (P <.05). The
      metabolism of IFN-alpha was significantly higher in kidney obtained at 9:00 PM
      than at 9:00 AM (P <.05). These findings support that choosing the most
      appropriate time of day for administration of IFN-alpha, associated with the
      rhythmicity of IFN-alpha receptor function and IFN-alpha pharmacokinetics, may
      increase the antiviral activity in experimental and clinical situations.

PMID- 10900224
TI  - Functional evidence for presence of PEPT2 in rat choroid plexus: studies with
      glycylsarcosine.
AB  - PEPT2 expression has been established in brain and, in particular, mRNA
      transcripts and PEPT2 protein have been identified in choroid plexus. However,
      there is little evidence for the functional presence of this peptide transporter
      in choroid plexus tissue. In this study, we examined the in vitro uptake of a
      model dipeptide, glycylsarcosine (GlySar), with whole tissue rat choroid plexus
      in artificial cerebrospinal fluid. Our findings are consistent with the known
      transport properties of PEPT2, including its proton dependence, lack of sodium
      effect, specificity, and high substrate affinity for dipeptides. Kinetic analysis
      showed saturable transport of GlySar with a Michaelis constant (K(m)) of 129 +/-
      32 microM and a maximum velocity (V(max)) of 52.8 +/- 3.6 pmol/mg/min. GlySar
      uptake (1.88 microM) was not inhibited by 1.0 mM concentrations of amino acids
      (glycine, sarcosine, L-histidine), organic acids and bases (4-acetamido-4'
      isothiocyanatostilbene-2,2'-disulfonic acid, tetraethylammonium), or non-alpha
      amino cephalosporins (cephaloridine, cephalothin). In contrast, di- and
      tripeptides (GlySar, glycylproline, glycylglycylhistidine), neuropeptides
      (carnosine), and alpha-amino cephalosporins (cefadroxil, cephalexin) inhibited
      the uptake of GlySar by 85 to 90% at 1.0 mM. These findings indicate that PEPT2
      is functionally active in choroid plexus and that it might play a role in
      neuropeptide homeostasis of cerebrospinal fluid. The ability of PEPT2 to
      transport drugs at the choroid plexus also may be important for future drug
      design, delivery, and tissue-targeting considerations.

PMID- 10900225
TI  - Functional compartmentalization of opioid desensitization in primary sensory
      neurons.
AB  - The cellular correlates of desensitization or tolerance are poorly understood. To
      address this, we studied acute and long-term mu-opioid desensitization, with
      respect to Ca(2+) currents, in cultured rat dorsal root ganglion (DRG) neurons.
      Exposure of DRG neurons to the mu-agonist [D-Ala(2),N-MePhe(4), Gly-ol(5)]
      enkephalin (DAMGO; 3 microM) reduced whole-cell currents approximately 35%, but
      with continued agonist application, 52% of the response was lost over 10 to 12
      min. In contrast, exposure of DRG neurons to DAMGO for 24 h resulted in a nearly
      complete loss of Ca(2+) channel regulation after washing and re-exposure to
      DAMGO. Responses to the gamma-aminobutyric acid(B) agonist baclofen were not
      affected in these neurons. Acute desensitization preferentially affected the
      voltage-sensitive component of mu-opioid and gamma-aminobutyric acid(B)
      responses. Facilitation of both the DAMGO- and baclofen-inhibited current by a
      strong depolarizing prepulse was significantly attenuated in acutely desensitized
      neurons. Because G(betagamma)-subunits mediate neurotransmitter-induced changes
      in channel voltage-dependent properties, these data suggest an altered
      interaction of the G(betagamma)-subunit with the Ca(2+) channel. Block of N-type
      Ca(2+) channels with omega-conotoxin GVIA revealed a component of the opioid
      response that did not desensitize over 10 min. We conclude that acute and long
      term mu-opioid desensitization in DRG neurons occurs by different mechanisms.
      Acute desensitization is heterologous and functionally compartmentalized: the
      pathway targeting non-N-type channels is relatively resistant to the early
      effects of continuous agonist exposure; the pathway targeting N-type channels in
      a largely voltage-insensitive manner is partially desensitized; and the pathway
      targeting N-type channels in a largely voltage-sensitive manner is completely
      desensitized.

PMID- 10900227
TI  - Elevated airway GSH resynthesis confers protection to Clara cells from
      naphthalene injury in mice made tolerant by repeated exposures.
AB  - Repeated exposures to Clara cell cytotoxicants, such as naphthalene (NA), render
      target cell populations resistant to further acute injury. Previous studies
      suggest that alterations in bioactivation enzymes in target sites (bronchioles)
      of tolerant mice are insufficient to account for the marked reduction in
      susceptibility. Mice were made tolerant by seven daily injections of NA. GSH in
      the terminal airways was 2.7-fold greater in tolerant mice than in vehicle
      controls and a NA (300 mg/kg) challenge dose did not produce injury. Tolerant
      mice, allowed to recuperate for 96 h after the seventh NA injection, were again
      susceptible to NA injury, and terminal airway GSH levels had declined to control
      levels. To determine whether alterations in GSH resynthesis account for
      tolerance, the activity of gamma-glutamylcysteine synthetase (gamma-GCS) was
      measured or mice were treated with a combination of buthionine sulfoximine (BSO),
      a gamma-GCS inhibitor, and NA. gamma-GCS activity was elevated in resistant
      airways of tolerant mice. Tolerant mice treated with both BSO and NA appeared as
      susceptible to injury as NA-challenged controls. We conclude that GSH is critical
      for Clara cell resistance to NA injury in tolerant mice because: 1) GSH levels in
      target airways from NA-tolerant animals are elevated; 2) after a 96-h
      recuperation period, tolerant mice had lower GSH levels and are again susceptible
      to NA injury; 3) alterations in the activity of gamma-GCS correspond with changes
      in susceptibility to NA injury; and 4) inhibition of gamma-GCS with BSO increases
      susceptibility to NA injury in tolerant mice.

PMID- 10900226
TI  - Hydroxyprolylserine derivatives JBP923 and JBP485 exhibit the antihepatitis
      activities after gastrointestinal absorption in rats.
AB  - It has been a desire to develop orally effective therapeutic agents that restore
      the liver function in chronic injury. Here we demonstrated that trans-4-L
      hydroxyprolyl-L-serine (JBP923) and cyclo-trans-4-L-hydroxyprolyl-L-serine
      (JBP485), which was previously isolated from hydrolysate of human placenta,
      exhibit potent antihepatitis activity after their oral administration. The
      increase in bilirubin concentration and activities of liver cytosolic enzymes in
      serum caused by alpha-naphthylisothiocyanate intoxication in rats were
      significantly countered both after i.v. and oral administration of these
      dipeptides, whereas glycyrrhizin, which has been used in the treatment of chronic
      hepatitis, is active only after its i.v. administration. Antihepatitis activity
      of dipeptides results, at least partially, from their direct effect on
      hepatocytes because glutamic-oxaloacetic transaminase and lactate dehydrogenase
      activities in the medium of hepatotoxin-exposed primary cultured hepatocytes were
      reduced by these compounds. When comparing the plasma concentration-time profile
      of JBP923 after its i.v., oral, and portal vein injection, it is suggested that
      JBP923 is almost completely absorbed from gastrointestinal lumen, and hepatic
      first-pass removal is minor. JBP923 inhibited the proton-dependent transport of
      glycylsarcosine in brush-border membrane vesicles, suggesting that peptide
      transport system(s) may recognize JBP923. Thus, these dipeptides are potent
      antihepatitis reagents that are still active after oral administration and may be
      useful for clinical applications.

PMID- 10900228
TI  - Hepatic and central nervous system cytochrome P450 are down-regulated during
      lipopolysaccharide-evoked localized inflammation in brain.
AB  - The effect of central nervous system inflammation on the levels and activity of
      hepatic and brain cytochrome P450 were examined in the rat. Brain ethoxyresorufin
      dealkylkase (EROD) was depressed during localized inflammatory responses evoked
      by lipopolysaccharide (LPS) injected into the lateral ventricle. This loss was
      accompanied by a concomitant loss of EROD activity and cytochrome P450 in liver.
      Similar losses in hepatic enzyme were observed for benzyloxy-resorufin and
      pentoxy-resorufin dealkylase (CYP2B) and chlorzoxazone hydroxylation (CYP2E).
      Protein levels of CYP2D and CYP2E1 but not CYP1A also were depressed. Similar
      i.p. doses of LPS had no effect on hepatic cytochrome P450, indicating that the
      hepatic effect was not caused by LPS leakage from the central nervous system.
      Also in support of this contention is that heat shock protein 27 was expressed
      throughout the brain by LPS given i.c. v. but was undetectable in the liver.
      Tumor necrosis factor-alpha given i.c.v. depressed EROD activity in the brain but
      this was not accompanied by a concomitant loss in the liver. Hepatic EROD did
      respond to the i.p. injection of tumor necrosis factor-alpha. The LPS-evoked loss
      in hepatic cytochrome P450 could not be prevented by blocking beta-receptor
      mediated sympathetic nerve activity. This study demonstrates that localized
      inflammatory responses in the brain cause a concomitant down-regulation of
      cytochrome P450 and drug-metabolizing activity in the liver and the brain. The
      effect on brain cytochrome P450 may be regulated via cytokine-mediated pathways
      but signaling to the liver does not involve a cytokine-mediated pathway nor a
      beta-receptor-mediated sympathetic nerve pathway.

PMID- 10900229
TI  - Behavioral activation induced by D(2)-like receptor stimulation during opiate
      withdrawal.
AB  - Withdrawal is a potent motivator of drug-seeking behavior in human opiate
      addicts. Paradoxically, opiate withdrawal reduces dopamine release and suppresses
      behavioral responding in several animal models of addiction. These findings pose
      critical questions about how a withdrawal state that depresses dopaminergic and
      behavioral functioning contributes to drug seeking. This study addressed this
      issue by investigating factors that increase behavioral activity during opiate
      withdrawal. Initial experiments revealed that the D(2)-like agonists
      propylnorapomorphine HCl (NPA; 0.05-0.4 mg/kg, i. p.) and quinpirole (0.2-0.4
      mg/kg, s.c.) each produced strong locomotor activating effects during opiate
      withdrawal that were not apparent in the absence of withdrawal. Concurrent
      stereotypy ratings indicated that these effects of NPA and quinpirole during
      withdrawal were not an indirect consequence of changes in the stereotypy-inducing
      effects of these drugs. Subsequent experiments showed that locomotion was not
      increased when opiate withdrawal was induced in the presence of the D(1)-like
      agonist SKF 38393 (1.0-8.0 mg/kg, i.p.), that the locomotor activation produced
      by NPA during withdrawal could be attenuated by the D(2)-like antagonist
      eticlopride (0.1-0.2 mg/kg, i.p.), and that locomotor activating effects of NPA
      could be observed when withdrawal was induced by extracting the implanted
      morphine pellets, but not when the NPA was given after naltrexone antagonism of
      acute morphine treatment in nondependent rats. These findings indicate that
      opiate withdrawal regulates the behavioral impact of D(2)-like receptor
      stimulation so that locomotion is markedly increased when these receptors are
      stimulated during periods of withdrawal. This potentiation may be important for
      facilitating behavioral responses during periods of opiate detoxification.

PMID- 10900230
TI  - Agonist-directed trafficking of porcine alpha(2A)-adrenergic receptor signaling
      in Chinese hamster ovary cells: l-isoproterenol selectively activates G(s).
AB  - In this study, we investigated the hypothesis of agonist-directed trafficking of
      receptor signaling for the alpha(2A)-adrenergic receptor (alpha(2A)-AR).
      alpha(2A)-ARs couple to both G(s) and G(i) to stimulate or inhibit adenylyl
      cyclase activity. Chinese hamster ovary-K1 cell lines expressing the porcine
      alpha(2A)-AR at high (alpha(2A)-H) and low (alpha(2A)-L) levels were used to
      estimate the relative efficacies (R.e.s) of a series of agonists for the G(s) and
      G(i) pathways. G(s)-mediated responses were measured after pertussis toxin
      treatment to inactivate G(i) in alpha(2A)-H, whereas G(i) responses were measured
      in alpha(2A)-L, where G(s) responses were absent. The full agonist UK-14,304
      showed a large receptor reserve for G(i) responses in alpha(2A)-H but little
      receptor reserve for G(s) responses in alpha(2A)-H or for G(i) responses in
      alpha(2A)-L. With the exception of l-isoproterenol (ISO), all agonists showed
      similar R.e.s at the alpha(2A)-AR for G(s) and G(i) responses, with rank orders
      of R.e.s as follows: l-epinephrine = l-norepinephrine = UK-14,304 > p
      aminoclonidine > or = BHT-920 > or = BHT-933 > clonidine = p-iodoclonidine > or =
      xylazine > or = guanabenz. Interestingly, ISO had the highest efficacy at the
      alpha(2A)-AR for activating G(s) versus G(i) (9-fold higher); however, it had low
      potency for both. By several criteria, the ISO response was mediated by the
      alpha(2A)-AR, supporting the hypothesis of agonist-directed trafficking of
      receptor signaling or agonist-specific G protein selectivity. In contrast, the
      apparent G(i) pathway selectivity of oxymetazoline appears to be mediated by an
      endogenous serotonergic receptor. It is intriguing that a classic beta-AR agonist
      that activates G(s) through beta(2)-ARs also appears to produce a G(s)-selective
      conformation of the G(i)-coupled alpha(2A)-AR.

PMID- 10900232
TI  - Histamine suppresses A-type potassium current in myenteric neurons from guinea
      pig small intestine.
AB  - Perforated patch-clamp methods for recording ionic currents in the whole-cell
      configuration were used to test the hypothesis that the ionic mechanisms for the
      excitatory actions of histamine on enteric neurons include suppression of A-type
      K(+) current (I(A)). Histamine and the selective histamine H(2) receptor agonist,
      dimaprit, reduced the amplitude of I(A) without affecting the slope factor for
      I(A) steady-state inactivation curves. Suppression of I(A) was restricted to
      after hyperpolarization-type myenteric neurons that were immunoreactive for
      calbindin. The selective histamine H(2) receptor antagonist cimetidine suppressed
      the action of histamine and dimaprit. Elevation of intraneuronal cAMP by
      forskolin, a membrane-permeant analog of cAMP, and treatment with a
      phosphodiesterase inhibitor suppressed I(A.) The results are consistent with the
      hypothesis that suppression of I(A) is part of the ionic mechanism responsible
      for elevation of excitability during both slow synaptic excitation and slow
      synaptic excitation-like responses evoked by paracrine mediators, such as
      histamine, in after hyperpolarization-type myenteric neurons.

PMID- 10900231
TI  - Radicicol suppresses expression of inducible nitric-oxide synthase by blocking
      p38 kinase and nuclear factor-kappaB/Rel in lipopolysaccharide-stimulated
      macrophages.
AB  - We show that radicicol, a fungal antibiotic, produces a marked inhibition of p38
      kinase, nuclear factor-kappaB/Rel (NF-kappaB/Rel), and inducible nitric-oxide
      synthase (iNOS) transcription by the macrophage line RAW 264.7 in response to
      lipopolysaccharide (LPS). Treatment of RAW 264.7 with radicicol inhibited LPS
      stimulated p38 kinase phosphorylation in a dose-related manner. iNOS
      transcription, which is regulated in part by the NF-kappaB/Rel family of
      transcription factors, has been shown to be under the control of the p38 kinase
      signaling cascade. Our data also show that the p38 kinase pathway is specifically
      involved in LPS-induced NF-kappaB/Rel activation and iNOS expression because NF
      kappaB/Rel DNA binding and iNOS mRNA production in the presence of a specific
      inhibitor of p38 kinase, SB203580, were dramatically diminished. In contrast,
      PD98059, a specific inhibitor of mitogen-activated protein kinase/extracellular
      signal-regulated protein kinase kinase 1 had no effect on NF-kappaB/Rel
      activation and iNOS expression. LPS-induced loss of inhibitory proteins IkappaB
      alpha and IkappaB-beta and translocation of p65, c-Rel, and p50 was inhibited by
      radicicol. Collectively, this series of experiments indicates that radicicol
      inhibits iNOS gene expression by blocking p38 kinase signaling. Due to the
      critical role that NO release plays in mediating inflammatory responses, the
      inhibitory effects of radicicol on iNOS suggest that this potent antifungal agent
      may represent a useful anti-inflammatory agent.

PMID- 10900233
TI  - Comparison of L-type calcium channel blockade by nifedipine and/or cadmium in
      guinea pig ventricular myocytes.
AB  - We tested the assumption that nifedipine blocks L-type calcium current [I(Ca(L))]
      at +10 mV and unmasks Na(+)/Ca(2+) exchange-triggered contractions in guinea pig
      isolated ventricular myocytes. Voltage-clamp pulses elicited I(Ca(L)) at +10 mV
      and evoked contractions in myocytes superfused with Tyrode's solution (35 degrees
      C). Nifedipine blocked I(Ca(L)) with an IC(50) of 0.3 microM; this decreased to
      50 nM at a holding potential of -40 mV, indicating preferential block of
      inactivated L-type Ca(2+) channels. Use-independent block of I(Ca(L)) increased
      with concentration (10-100 microM) and application time when nifedipine was
      rapidly applied (t(1/2) = approximately 0.2 s) during rest intervals (5-30 s).
      The fraction of use-dependent block of I(Ca(L)) diminished with increasing drug
      concentration. Nifedipine also accelerated I(Ca(L)) inactivation on the first
      test pulse. The combination of 30 microM nifedipine/30 microM Cd(2+) (Nif 30/Cd
      30) was as effective as 100 microM nifedipine to suppress I(Ca(L)) on the first
      test pulse at +10 mV. The incidence of complete block of contractions, as for
      complete block of I(Ca(L)), increased as a function of nifedipine concentration
      and application time. Neither nifedipine nor Nif 30/Cd 30 affected Na(+)/Ca(2+)
      exchange current at +10 to +100 mV. Contractions at +100 mV, although as large as
      those at +10 mV, were delayed in onset and resistant to nifedipine or Nif 30/Cd
      30. We conclude that nifedipine-sensitive I(Ca(L)) triggers contractions at +10
      mV, whereas nifedipine-resistant Na(+)/Ca(2+) exchange current initiates those at
      +100 mV.

PMID- 10900234
TI  - Differential effect of local infusion of serotonin reuptake inhibitors in the
      raphe versus forebrain and the role of depolarization-induced release in
      increased extracellular serotonin.
AB  - Systemic administration of selective serotonin reuptake inhibitors (SSRIs)
      elicits larger increases in serotonin (5-HT) in raphe than in forebrain sites.
      Because serotonergic neuronal activity is suppressed, the mechanism underlying
      SSRI-induced increases in extracellular 5-HT is unclear. This study determined
      whether local infusion of SSRIs also elicited regionally selective increases in
      extracellular 5-HT, and whether changes depended on serotonergic neuronal
      depolarization. Conventional microdialysis methods were used to measure 5-HT in
      dorsal raphe (DRN), median raphe, nucleus accumbens (NAcc), and frontal cortex of
      unanesthetized rats. During infusion of SSRIs into each site, the maximum
      response was an approximately 6- to 7-fold increase in 5-HT in NAcc and frontal
      cortex, and an approximately 20-fold increase in DRN and median raphe. The larger
      increase in 5-HT in raphe was confirmed using zero-net-flux microdialysis. In
      NAcc, baseline 5-HT was 0.7 nM, and levels increased to a maximum of 3.1 nM
      during infusion of the SSRI citalopram. Baseline 5-HT in DRN was greater, 1.3 nM,
      and increased to 12.4 nM in response to citalopram. Consistent with evidence that
      autoreceptor activation inhibits serotonergic neuronal discharge, SSRI infusion
      into DRN produced a moderate decrease in 5-HT in NAcc. However, increases in 5-HT
      in DRN elicited by SSRI infusion were attenuated by 8
      hydroxydipropylaminotetralin and tetrodotoxin. These data indicate that
      depolarization-dependent 5-HT release was not fully inhibited during SSRI
      infusion into DRN. In summary, SSRIs produce larger increases in extracellular 5
      HT in raphe than in forebrain sites. Increases depend in part on depolarization
      induced release, which may be greater in raphe than in forebrain.

PMID- 10900235
TI  - A study of the intestinal absorption of an ester-type prodrug, ME3229, in rats:
      active efflux transport as a cause of poor bioavailability of the active drug.
AB  - The intestinal absorption of a prodrug is affected by a number of factors, such
      as its membrane permeability, stability in the gut lumen, and conversion to the
      parent drug in enterocytes. We evaluated the absorption of ME3229, an ester-type
      prodrug of a hydrophilic glycoprotein IIb/IIIa antagonist. Although the
      octanol/water distribution coefficient and permeability across a Caco-2 cell
      monolayer of ME3229 was high enough for us to expect good oral absorption, less
      than 10% of the dose was absorbed in rats. To clarify this unexpected outcome, we
      evaluated the rate of its disappearance from the gut lumen (V1), its degradation
      in the gut lumen (V(deg)), uptake into enterocytes (V(uptake)), and appearance in
      the mesenteric vein (V2) by using a single-pass perfusion technique in
      combination with an in vitro metabolism study. Our data suggested that ME3229
      crossed the apical membrane and was taken up into enterocytes at a rate
      compatible with its lipophilicity, but that only a small fraction of the
      metabolites formed in enterocytes reached the mesenteric vein, primarily
      attributable to efflux into the intestinal lumen. Transport of the main
      metabolite across rat intestinal tissue mounted on an Ussing chamber suggested
      that an active efflux system pumped out any ionic metabolite(s) present.

PMID- 10900236
TI  - Chronic administration of the selective corticotropin-releasing factor 1 receptor
      antagonist CP-154,526: behavioral, endocrine and neurochemical effects in the
      rat.
AB  - Corticotropin-releasing factor 1 (CRF(1)) receptor antagonists may represent a
      novel group of drugs for the pharmacotherapy of depression and/or anxiety
      disorders. We have investigated the behavioral, endocrine, and neurochemical
      effects of chronic administration of a selective CRF(1) receptor antagonist, CP
      154,526. After 9 to 10 days of treatment with CP-154,526 (3.2 mg/kg/day),
      defensive withdrawal behavior was significantly decreased suggesting anxiolytic
      activity. In animals treated for 14 days with the low dose of CP-154,526, serum
      corticosterone concentrations returned to baseline levels faster after
      application of an airpuff startle. Using in situ hybridization, no changes in
      CRF(1) receptor mRNA expression were detected in parietal cortex, basolateral
      amygdala, or cerebellum after chronic treatment with CP-154,526. A dose-dependent
      decrease in CRF mRNA expression was observed in the hypothalamic paraventricular
      nucleus (PVN) and the Barrington's nucleus, an effect that was significant at the
      high but not the low dose of CP-154,526. CP-154,526 did not alter central CRF(2A)
      receptor binding or mRNA expression, or urocortin mRNA expression. The present
      findings suggest that chronic administration of CP-154, 526 produces anxiolytic
      like effects but no evidence of adrenal insufficiency. Previous postmortem
      studies revealed increased CRF peptide and mRNA levels in the PVN of depressed
      patients, which may mediate the hyperactivity of the hypothalamic-pituitary
      adrenal axis observed in such patients. In view of a possible use for CRF(1)
      receptor antagonists in the treatment of depression, the present finding that CP
      154,526 decreases CRF synthesis in the PVN is of considerable interest.

PMID- 10900237
TI  - Vascular reactivity of isolated thoracic aorta of the C57BL/6J mouse.
AB  - We characterized the thoracic aorta from the C57BL/6J mouse, a strain used
      commonly in the generation of genetically altered mice, in response to vasoactive
      substances. Strips of aorta were mounted in tissue baths for measurement of
      isometric contractile force. Cumulative concentration-response curves to agonists
      were generated to observe contraction, or relaxation in tissues contracted with
      phenylephrine or prostaglandin F(2alpha) (PGF(2alpha)). In endothelium-denuded
      strips, the order of agonist contractile potency (-log EC(50) [M]) was
      norepinephrine > phenylephrine = 5-hydroxytryptamine > dopamine > PGF(2alpha) >
      isoproterenol > KCl. Angiotensin II and endothelin-1 were weakly efficacious (15%
      of maximum phenylephrine contraction), as were UK14,304, clonidine, histamine,
      and adenosine. In endothelium-intact strips, agonists still caused contraction
      and both angiotensin II and endothelin-1 remained ineffective. In experiments
      focusing on angiotensin II, angiotensin II-induced contraction was abolished by
      the AT(1) receptor antagonist losartan (1 microM) but was not enhanced in the
      presence of the AT(2) receptor antagonist PD123319 (0.1 microM), tyrosine
      phosphatase inhibitor orthovanadate (1 microM) or when angiotensin II was given
      noncumulatively. Prazosin abolished isoproterenol-induced contraction and did not
      unmask isoproterenol-induced relaxation. Angiotensin II and endothelin-1 did not
      cause endothelium-dependent or -independent relaxation in phenylephrine- or
      PGF(2alpha)-contracted tissues. Acetylcholine but not histamine, dopamine, or
      adenosine caused an endothelium-dependent vascular relaxation. These experiments
      provide information as to the vascular reactivity of the normal mouse thoracic
      aorta and demonstrate that the mouse aorta differs substantially from rat aorta
      in response to isoproterenol, angiotensin II, endothelin-1, histamine, and
      adenosine.

PMID- 10900238
TI  - Protein kinase C and phosphatase inhibitors block the ability of angiotensin I
      converting enzyme inhibitors to resensitize the receptor to bradykinin without
      altering the primary effects of bradykinin.
AB  - Angiotensin I-converting enzyme (kininase II) inhibitors (ACEis) are very widely
      used to treat cardiac conditions and nephropathies, but some of their beneficial
      activities cannot be attributed to enzyme inhibition alone. We investigated the
      effects of ACEis on the human bradykinin (BK) B(2) receptor expressed in Chinese
      hamster ovary cells transfected with the cDNA of human receptor and ACE, and on
      human pulmonary endothelial cells that constitutively express both proteins. BK
      and its ACE-resistant peptide analog activated the B(2) receptor to release
      arachidonic acid and elevate [Ca(2+)](i) and subsequently desensitized it. The
      release of arachidonic by BK was independent of extracellular Ca(2+). BK enhanced
      phosphorylation of the immunoprecipitated B(2) receptor but enalaprilat
      significantly reduced it. ACEi resensitized the receptor by initiating a cross
      talk between the receptor and ACE. Protein kinase C and phosphatase inhibitors
      distinguished the signaling by the receptor when activated first by BK from BK
      acting on the resensitized receptor. Treatment of cells with 1 microM calphostin,
      100 nM staurosporine, 100 nM calyculin, or 500 nM okadaic acid did not affect
      either one of the primary actions of BK on the receptor. Protein kinase C or
      phosphatase inhibitors, however, blocked the effects of BK on the receptor
      resensitized by enalaprilat or ramiprilat. The experiments clearly differentiate
      the primary activation of the receptor by BK from activation of the resensitized
      receptor after ACEi treatment. The existence of an intermediate component
      involved in the action of ACEis to enhance release of vasoactive mediators by BK
      is suggested.

PMID- 10900239
TI  - Increased mesolimbic GABA concentration blocks heroin self-administration in the
      rat.
AB  - Opiate reinforcement has been hypothesized to be mediated by an inhibition of
      mesolimbic gamma-aminobutyric acid (GABA) release that subsequently disinhibits
      ventral tegmental area (VTA) dopamine neurons. In support of this hypothesis,
      this study demonstrates that when administered directly into the lateral
      ventricle, the VTA, or the ventral pallidum, but not the nucleus accumbens, gamma
      vinyl-GABA (GVG, an irreversible GABA-transaminase inhibitor, 20-50 microg) dose
      dependently blocked heroin (0.06 mg/kg) self-administration (SA), as assessed by
      an increase in heroin SA at low doses of GVG and an initial increase followed 1
      to 2 h later by a blockade of heroin SA at higher GVG doses. This effect lasted 3
      to 5 days. In drug-naive rats, intra-VTA GVG pretreatment also prevented or
      delayed acquisition of heroin SA for 2 days. This GVG effect was prevented or
      reversed by systemic or intra-VTA pretreatment with the GABA(B) antagonist 2
      hydroxysaclofen, but not the GABA(A) antagonist bicuculline. Similarly,
      coadministration of heroin with aminooxy-acetic acid (1-4 mg/kg) or ethanolamine
      O-sulfate (50-100 mg/kg), two reversible GABA transaminase inhibitors, dose
      dependently reduced heroin reinforcement. Coadministration of (+/-)-nipecotic
      acid (0.1-5 mg/kg) with heroin, or intra-VTA or -ventral pallidum pretreatment
      with (+/-)-nipecotic acid (10 microg) or NO-711 (2 microg), two GABA uptake
      inhibitors, significantly increased heroin SA behavior, an effect also blocked by
      systemic 2-hydroxysaclofen, but not bicuculline. Taken together, these
      experiments, for the first time, demonstrate that pharmacological elevation of
      mesolimbic GABA concentration blocks heroin reinforcement by activating GABA(B)
      receptors, supporting the GABAergic hypothesis of opiate reinforcement and the
      incorporation of GABA agents in opiate abuse treatment.

PMID- 10900240
TI  - Cantharidin enhances norepinephrine-induced vasoconstriction in an endothelium
      dependent fashion.
AB  - In this study we characterized the effects of the protein phosphatase (PP) type 1
      and type 2A inhibitor cantharidin (Cant) and its structural analogs cantharidic
      acid and endothall on PP activity, force of contraction, and myosin light chain
      phosphorylation in rat aorta. All compounds inhibited PP activity in homogenates
      of rat aorta with a rank order of potency of Cant = cantharidic acid > endothall.
      However, only Cant increased force of contraction and myosin light chain
      phosphorylation in intact isolated rat aortic rings. Based on these findings, we
      investigated the effects of Cant on alpha-adrenoceptor-mediated vasoconstriction.
      Cant (1 and 3 microM) enhanced norepinephrine-induced contraction in endothelium
      intact rat aorta. In contrast, Cant did not affect norepinephrine-induced
      contraction in endothelium-denuded rat aorta. We suggest that inhibition of PP1
      and/or PP2A activities by Cant enhances vascular contractility in endothelium
      intact rat aorta by increasing the phosphorylation state of endothelial
      regulatory proteins.

PMID- 10900241
TI  - Presynaptic muscarinic facilitation of parasympathetic neurotransmission after
      sympathectomy in the rat choroid.
AB  - The effect of sympathectomy on parasympathetic regulation of ocular perfusion was
      investigated. Uveal blood flow through the vortex veins was measured by laser
      Doppler flowmetry during electrical stimulation of the superior salivatory
      nucleus, which activates ocular parasympathetic nerves, in adult rats with intact
      innervation and 2 days or 6 weeks after excision of the ipsilateral superior
      cervical ganglion. In all groups, parasympathetic stimulation produced comparable
      increases in flux, which were abolished by the selective neuronal nitric-oxide
      synthetase inhibitor, 1-(2-trifluoromethylphenyl) imidazole. Atropine had no
      effect in control and acutely sympathectomized rats but abolished the flux
      increase in four of six chronically sympathectomized animals, and 1-(2
      trifluoromethylphenyl) imidazole eliminated the residual response. The muscarinic
      receptor agonist bethanechol did not affect basal flow in control or
      sympathectomized rats. However, bethanechol enhanced parasympathetically mediated
      vasodilation, but only in rats studied at 6 weeks after sympathectomy, a finding
      consistent with the appearance of muscarinic prejunctional facilitation of
      nitrergic transmission. In chronically sympathectomized rats, the M(2) and M(4)
      receptor antagonists methoctramine and tropicamide did not affect choroidal flow
      during parasympathetic activation. However, pirenzepine increased flux, implying
      the presence of M(1) inhibitory autoreceptors on these nerves.
      Parasympathetically mediated increased flux was partially blocked by the M(3)
      antagonist 4-diphenylacetoxy-N-methylpiperdine, and the remaining vasodilation
      was blocked by atropine. We conclude that parasympathetic prejunctional
      facilitatory M(3) and probably M(5) receptors adopt a crucial role after chronic
      sympathectomy in maintaining nitrergic vasodilatory ocular neurotransmission in
      the face of down-regulated nitric oxide transmitter mechanisms.

PMID- 10900243
TI  - Ethanol inhibition of N-methyl-D-aspartate responses involves presynaptic gamma
      aminobutyric acid(B) receptors.
AB  - Ethanol alters N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid subtype A
      (GABA(A)) receptor-mediated neurotransmission. We have previously demonstrated
      that GABA(B) receptor blockade uncovers ethanol enhancement of GABA(A) responses
      in the hippocampus. Therefore, we evaluated in vivo and in vitro the role of
      GABA(B) receptors in ethanol-induced inhibition of neuronal activity as well as
      NMDA responses in the hippocampus, ventral tegmental area (VTA), and nucleus
      accumbens (NAcc), three brain areas with known sensitivity to low doses of
      ethanol. In vivo, in situ microelectrophoretic application of ethanol enhanced
      inhibition of VTA GABA neuron firing rate by the GABA(B) agonist baclofen and
      reduced inhibition of VTA GABA firing rate by the GABA(A) agonist muscimol. The
      GABA(B) antagonist CGP35348 blocked baclofen- and ethanol-induced, but not
      muscimol-induced, reduction of NMDA-activated firing of hippocampal hilar mossy
      cells, hilar interneurons, and VTA GABA neurons, as well as ethanol inhibition of
      NMDA receptor-sensitive, amygdala-driven NAcc neurons. We performed in vitro
      studies in NAcc slices to evaluate the mechanism of GABA(B) receptor-mediated
      ethanol inhibition of NMDA neurotransmission. In the presence of the non-NMDA
      receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and the GABA(A) receptor
      antagonist bicuculline, superfusion of the GABA(B) antagonist CGP55845 blocked
      ethanol (66 mM) inhibition of evoked NMDA receptor-mediated excitatory
      postsynaptic potentials. However, CGP55845 did not significantly affect ethanol
      inhibition of NMDA currents produced by pressure application of NMDA or non-NMDA
      glutamatergic excitatory postsynaptic potentials evoked in the presence of the
      bicuculline and the NMDA antagonist DL-2-amino-5-phosphonovalerate. Taken
      together, these findings suggest that the sensitivity of NMDA receptor-mediated
      neurotransmission to ethanol is regulated by GABA(B) receptors, possibly at
      presynaptic sites.

PMID- 10900242
TI  - Mahogany (1377-1428) enters brain by a saturable transport system.
AB  - The mouse mahogany gene encodes a protein that is involved in the suppression of
      diet-induced obesity. We studied the ability of its widely conserved C-terminal
      fragment to cross the blood-brain barrier (BBB) in mice. Multiple-time regression
      analysis showed that the entry rate (K(i)) of (125)I-mahogany (1377-1428) from
      blood-to-brain was 5.5 x 10(-4) ml/g. min. After coinjection of unlabeled
      mahogany (1377-1428), the K(i) was significantly decreased, showing the self
      inhibition characteristic of a saturable transport mechanism. The excess mahogany
      (1377-1428) did not change the influx rate of (99m)Tcalbumin, the vascular
      control, indicating a lack of disruption of the BBB. Statistically significant
      cross-inhibition was not seen with agouti-related protein (83-132), melanin
      concentrating hormone, epidermal growth factor, leptin, a melanocortin-4 receptor
      antagonist, or alpha-melanocyte-stimulating hormone. HPLC showed that most of the
      injected (125)I-mahogany (1377-1428) reached the brain intact, and capillary
      depletion with washout showed that most of it reached the parenchyma. There was
      no brain-to-blood efflux system for mahogany (1377-1428) but rather retention
      after i.c.v. administration, and the octanol/buffer partition coefficient showed
      low lipophilicity. Thus, the results show that the C-terminal peptide product
      encoded by the mahogany gene crosses the BBB by a transport mechanism that is
      saturable. The ability of this system to be regulated indicates the therapeutic
      potential of mahogany (1377-1428) in the treatment of obesity.

PMID- 10900244
TI  - Functional properties of transgenic mouse hearts overexpressing both
      calsequestrin and the Na(+)-Ca(2+) exchanger.
AB  - Overexpression of calsequestrin (CSQ) induces severe cardiac hypertrophy, whereas
      overexpression of Na(+)-Ca(2+) exchanger (NCX) does not affect cardiac weight. To
      investigate a possible beneficial effect of NCX in hypertrophy, we produced
      transgenic mice overexpressing both NCX and CSQ (NCX/CSQ). Surprisingly, these
      mice developed severe heart failure. The heart/body weight ratio was enhanced and
      the mRNA expression of ANF, as a marker of hypertrophy, was highest in double
      transgenic mice. In isolated muscle strips, the basal relaxation time was
      prolonged in CSQ and NCX/CSQ mice. Moreover, in the presence of caffeine, force
      of contraction was increased only in CSQ and NCX/CSQ and was accompanied by
      elevated diastolic tension. In some respects, however, additional overexpression
      of NCX altered the CSQ phenotype into the wild-type phenotype. The expression of
      sarcoplasmic reticulum (SR)-Ca(2+)-ATPase and phospholamban, proteins involved in
      the Ca(2+) uptake of the SR, were only increased in CSQ, indicating a possible
      influence of NCX in the regulation of SR-Ca(2+) uptake proteins. The Ca(2+)
      transients and the L-type Ca(2+) currents in the presence of caffeine were very
      large in CSQ, but smaller increases were noted in double transgenic mice.
      Therefore, the successful co-overexpression of CSQ and NCX in these mice provides
      a novel model in which to investigate the interaction of proteins tightly linked
      to maintain Ca(2+) homeostasis.

PMID- 10900245
TI  - Glucocorticoid-induced alterations of renal sulfate transport.
AB  - Glucocorticoid administration decreases renal sodium/phosphate cotransport in the
      proximal tubule due to a down-regulation of the sodium/phosphate cotransporter
      but has no effect on the sodium-dependent transport of glucose or proline. The
      objectives of the present investigation were to determine the effects of the
      glucocorticoid methylprednisolone (MPL) on 1) inorganic sulfate renal clearance
      in rats in vivo, 2) sodium/sulfate cotransport in kidney cortex membrane
      vesicles, and 3) the cellular mechanism of the MPL-induced alterations in sulfate
      renal transport. Male adrenalectomized Wistar rats received an i.v. dose of 50
      mg/kg MPL or the vehicle. Urine samples were collected for 12 h after the
      administration of MPL, and blood samples were collected at the midpoint of the
      urine collection. Other animals were sacrificed at 4, 6, and 12 h after MPL
      administration, and the kidney cortex was removed for RNA or membrane
      preparations. Kidney cortex sodium/sulfate cotransporter (NaSi-1) mRNA levels
      were determined by reverse transcription-polymerase chain reaction and NaSi-1
      protein levels were determined by enzyme-linked immunosorbent assay. The urinary
      excretion rate and renal clearance of sulfate were significantly increased in MPL
      treated animals (144.0 +/- 27.0 versus 65.3 +/- 21.3 micromol/12 h/kg and 0.208
      +/- 0.038 versus 0. 078 +/- 0.025 ml/min/kg, mean +/- S.E., n = 9-12 in treated
      versus control). The V(max) value for sodium-dependent sulfate transport in brush
      border membrane vesicles (representing reabsorption in the proximal tubules) was
      significantly decreased in MPL-treated animals compared with controls (0.68 +/-
      0.07 versus 0.88 +/- 0.05 nmol/mg of protein/10 s, mean +/- S.E.). There was no
      change in the K(m) value for sodium/sulfate cotransport in brush-border membrane
      and no change in sulfate/anion exchange in basolateral membrane vesicles.
      Membrane fluidity in brush border membrane and basolateral membrane vesicles,
      determined by the fluorescence polarization of 1, 6-diphenyl-1,3,5-hexatriene was
      unaltered by MPL treatment. NaSi-1 mRNA levels were significantly decreased at 4
      and 6 h, but not 12 h, after MPL administration, whereas NaSi-1 protein
      expression was significantly decreased at 4, 6, and 12 h. Therefore, MPL
      treatment increases the renal clearance of inorganic sulfate, at least in part,
      due to down-regulation of NaSi-1 mRNA and protein expression in the kidney.

PMID- 10900246
TI  - Attenuation of O(6)-methylguanine-DNA methyltransferase activity and mRNA levels
      by cisplatin and temozolomide in jurkat cells.
AB  - The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is
      important in cellular resistance to certain alkylating antitumor agents such as
      the methylating drug temozolomide (TMZ). To provide a more rational basis for
      clinical combinations with another commonly used drug, cisplatin, we assessed the
      modulation of MGMT protein and mRNA levels in the human leukemic cell line Jurkat
      after treatment with these agents. Cisplatin decreased MGMT activity in a time-
      and dose-dependent manner, with maximal suppression (50%) observed 24 h after
      treatment with 25 microM cisplatin. This was probably the result of decreased
      transcription of the MGMT gene, because there was an earlier nadir of MGMT mRNA
      levels after cisplatin treatment and neither cisplatin nor DNA reacted with
      cisplatin in vitro was able to inhibit MGMT activity in an in vitro assay. TMZ
      alone depleted MGMT activity in a time- and dose-dependent manner with almost
      complete loss of activity occurring immediately after treatment with 500 microM
      TMZ. Combinations of cisplatin (12.5 microM) and TMZ (250 microM) caused
      substantial and prolonged MGMT depletion with recovery to only 30% of
      pretreatment levels by 48 h. These results suggest that the clinical efficacy of
      TMZ and cisplatin may be improved by appropriate schedules of combinations of
      these agents.

PMID- 10900247
TI  - 5-Hydroxytryptamine(7) receptor activation decreases slow afterhyperpolarization
      amplitude in CA3 hippocampal pyramidal cells.
AB  - The 5-hydroxytryptamine(7) (5-HT(7)) receptor was originally defined by molecular
      biology techniques. The 5-HT(7) receptor protein and mRNA are found in brain
      areas, such as the CA3 subfield of the hippocampus, that are involved in various
      neuropsychiatric disease states. No functional response has previously been
      attributed to activation of the 5-HT(7) receptor in any of these brain areas.
      Calcium spike-induced slow afterhyperpolarizations (sAHP) were recorded from CA3
      hippocampal pyramidal cells using intracellular recording techniques in a brain
      slice preparation maintained in vitro. A concentration-dependent inhibition of
      the sAHP amplitude was obtained when 5-HT was used as the agonist. To identify
      whether the 5-HT(7) receptor was one of the receptors mediating the inhibition of
      the sAHP amplitude, 5-HT agonists and antagonists were tested in the presence of
      WAY-100635 and GR-113808 to block 5-HT(1A) and 5-HT(4) receptor activation,
      respectively. The rank order potency of the agonists was 5-carboxyamidotryptamine
      (5-CT) > 5-HT > 5-methoxytryptamine (5-MeOT). Other agonists with high affinity
      at 5-HT(2), 5-HT(3), 5-HT(1B), 5-HT(1D), or 5-HT(6) receptors did not produce any
      response when tested at 10 microM. Ritanserin, mesulergine, and SB-269770 were
      competitive antagonists of the 5-CT inhibition of sAHP amplitude, with affinity
      (pA(2)) values of 6.8, 7. 9, and 8.8, respectively. Methiothepin was also an
      effective antagonist but was insurmountable. Other antagonists with affinity for
      the 5-HT(2), 5-HT(3), or 5-HT(6) receptor had no effect. Based on the rank order
      potency of the agonists and antagonists, one of the receptors that mediates the
      decrease in sAHP amplitude in CA3 hippocampal pyramidal cells was concluded to be
      the 5-HT(7) receptor.

PMID- 10900248
TI  - Dopamine D1- and D2-like receptor mechanisms in relapse to cocaine-seeking
      behavior: effects of selective antagonists and agonists.
AB  - Dopaminergic mechanisms are thought to be critical in mediating relapse to
      cocaine-seeking behavior. This study examined the different roles of D1- and D2
      like receptor mechanisms in the relapse process. Squirrel monkeys were given
      extended histories of i. v. cocaine self-administration under conditions in which
      responding was maintained jointly by response-contingent cocaine injections and a
      cocaine-paired visual stimulus (second-order schedule). Responding was then
      extinguished by substituting saline for cocaine injections and omitting
      presentations of the cocaine-paired stimulus. Subsequently, noncontingent priming
      injections of cocaine combined with restoration of the cocaine-paired stimulus
      induced dose-dependent reinstatement of drug-seeking behavior, with response
      rates approaching those maintained by active cocaine self-administration. The
      priming effects of cocaine were attenuated by several D1- and D2-like receptor
      antagonists and low efficacy agonists but not by the D3-preferring antagonists UH
      232 and AJ-76. The priming effects of cocaine were mimicked by the D2-like
      receptor agonists R(-)-propylnorapomorphine hydrochloride (NPA) and quinpirole,
      less consistently by 7-OH-DPAT, and not by the D1-like receptor agonists SKF
      81297 and SKF-82958, the D3-preferring agonist PD-128,907, or any low efficacy
      agonist. Cotreatment with NPA, PD-128,907, and 7-OH-DPAT did not alter
      reinstatement of drug-seeking behavior induced by a maximally effective priming
      dose of cocaine, whereas cotreatment with D1-like receptor agonists attenuated
      the priming effects of cocaine. The results suggest that D1- and D2-like
      receptors play fundamentally different roles in the relapse process. Although
      stimulation of D2-like, but probably not D3-like, receptors appears necessary for
      induction of relapse, either stimulation or blockade of D1-like receptors appears
      to be inhibitory with respect to relapse.

PMID- 10900249
TI  - The novel 5-Hydroxytryptamine(1A) antagonist LY426965: effects on nicotine
      withdrawal and interactions with fluoxetine.
AB  - LY426965 [(2S)-(+)-1-cyclohexyl-4-[4-(2-methoxyphenyl)-1-piperazinyl]2-methyl- 2
      phenyl-1-butanone monohydrochloride] is a novel compound with high affinity for
      the cloned human 5-hydroxytryptamine (HT)(1A) receptor (K(i) = 4.66 nM) and 20
      fold or greater selectivity over other serotonin and nonserotonin receptor
      subtypes. Both in vitro and in vivo studies indicate that LY426965 is a full
      antagonist and has no partial agonist properties. LY426965 did not stimulate
      [(35)S]guanosine-5'-O-(3-thio) triphosphate (GTPgammaS) binding to homogenates of
      cells expressing the cloned human 5-HT(1A) receptor in vitro but did inhibit 300
      nM 5-HT-stimulated [(35)S]GTPgammaS binding with a K(i) value of 3.07 nM. After
      both p.o. and s.c. administration, LY426965 blocked the lower lip retraction,
      flat body posture, hypothermia, and increase in rat serum corticosterone induced
      by the 5-HT(1A) agonist 8-OH-DPAT (8-hydroxy-2-dipropylaminotetralin). In
      pigeons, LY426965 dose-dependently blocked the stimulus cue induced by 8-OH-DPAT
      but had no 8-OH-DPAT-like discriminative properties. LY426965 completely reversed
      the effects of nicotine withdrawal on the auditory startle reflex in rats. In
      microdialysis experiments, LY426965 administered together with fluoxetine
      significantly increased extracellular levels of serotonin above those achievable
      with fluoxetine alone. In electrophysiological studies, the administration of
      LY426965 produced a slight elevation of the firing rate of 5-HT neurons in the
      dorsal raphe nucleus of anesthetized rats and both blocked and reversed the
      effects of fluoxetine on 5-HT neuronal activity. These preclinical results
      indicate that LY426965 is a selective, full 5-HT(1A) antagonist that may have
      clinical use as pharmacotherapy for smoking cessation and depression and related
      disorders.

PMID- 10900250
TI  - Type 4 phosphodiesterase inhibitors attenuate respiratory syncytial virus-induced
      airway hyper-responsiveness and lung eosinophilia.
AB  - Viral respiratory infections are considered one of the triggers of exacerbations
      of asthma. In a model of virus-induced airway hyper-responsiveness (AHR), mice
      infected with human respiratory syncytial virus (RSV) were shown to develop AHR
      accompanied by lung eosinophilia. Inhibitors of cyclic nucleotide
      phosphodiesterase (PDE) have been shown to affect airway responsiveness and
      pulmonary allergic inflammation. In this study, we assessed the effects of type 4
      PDE (PDE4) inhibitors on AHR following RSV infection and compared them with a
      PDE3 inhibitor. In mice infected by intranasal inoculation of RSV, treatment with
      the PDE4 inhibitor rolipram or Ro-20-1724 reduced both AHR and the eosinophil
      infiltration of the airways. In contrast, the PDE3 inhibitor, milrinone, did not
      influence airway responsiveness or eosinophilic inflammation. These results
      demonstrate that PDE4 inhibitors can modulate RSV-induced AHR and lung
      eosinophilia and indicate that they have a potential role in treating
      exacerbations of asthma triggered by viral infection.

PMID- 10900252
TI  - Pharmacokinetics of sodium tungstate in rat and dog: a population approach.
AB  - Sodium tungstate has been found to correct hyperglycemia in insulin- and
      noninsulin-dependent models of diabetes when administered in drinking fluid with
      a low degree of toxicity; thus, it provides a potential treatment for diabetes.
      In the present report, pharmacokinetic studies with sodium tungstate were carried
      out in the Sprague-Dawley rat and beagle dog. This drug was administered either
      i.v. (8.97 mg/kg in rat; 25 and 50 mg/kg in dog) or orally in the form of
      solution (35.9 and 107.7 mg/kg in rat; 25 and 50 mg/kg in dog). Tungsten was
      quantified using an inductively coupled plasma method. Pharmacokinetic parameters
      were estimated using a population approach. Sodium tungstate followed first order
      kinetics, and plasma concentration-versus-time data were adequately described by
      a two-compartment model. In rat, bioavailability was high (92%), whereas it was
      lower in dog (approximately 65%). The total volume of distribution expressed by
      unit of body weight was much higher when the animal was smaller (0.46 l/kg in rat
      versus 0.23 l/kg in dog). The total body clearance normalized by weight, 0.19
      l/h/kg in rat versus 0.043 l/h/kg in dog, changed as for the volume of
      distribution. The elimination half-life was two times higher in dog
      (approximately 4 h) than in rat (approximately 1.7 h). In the range of 35.9 to
      107.7 mg/kg after oral administration in rat and 25 to 50 mg/kg after oral and
      i.v. administration in dog, tungsten plasma concentrations increased in
      proportion to dose.

PMID- 10900251
TI  - Cannabinoids cause central sympathoexcitation and bradycardia in rabbits.
AB  - Systemically administered cannabinoids elicit marked cardiovascular effects, and
      the role of the central and the peripheral nervous system in these effects is not
      clarified. The aim of this study was to characterize the actions of cannabinoids
      on cardiovascular regulatory centers in conscious rabbits. A catheter for
      administration of drugs into the cisterna cerebellomedullaris and an electrode
      for recording renal sympathetic nerve activity were implanted under halothane
      anesthesia. Experiments were carried out later in conscious animals. Two
      cannabinoid receptor agonists were injected intracisternally: the
      aminoalkylindole WIN55212-2 (0.1, 1, and 10 microg kg(-1)) and the bicyclic
      Delta(9)-tetrahydrocannabinol analog CP55940 (0.1, 1, and 10 microg kg(-1)).
      WIN55212-2 and CP55940 dose dependently increased renal sympathetic nerve
      activity and the plasma noradrenaline concentration and also lowered the heart
      rate. The highest doses of WIN55212-2 and CP55940 increased blood pressure. In
      contrast, intracisternal injection of WIN55212-3 (0.1, 1, and 10 microg kg(-1)),
      an enantiomer of WIN55212-2 with very low affinity for cannabinoid binding sites,
      had no effects. The CB(1) cannabinoid receptor antagonist SR141716A (0.5 mg kg(
      1), i.v. ) attenuated the effects of intracisternally administered WIN55212-2
      (0.1, 1, and 10 microg kg(-1)). The results indicate that cannabinoids, acting
      directly on cardiovascular regulatory centers, elicit sympathoactivation and
      bradycardia. These effects were likely mediated by CB(1) cannabinoid receptors,
      because they were elicited by two cannabinoid agonists belonging to different
      chemical classes (WIN55212-2 and CP55940), but not by the inactive enantiomer
      WIN55212-3, and because they were attenuated by the CB(1) cannabinoid receptor
      antagonist SR141716A.

PMID- 10900253
TI  - Protection against myocardial dysfunction induced by global ischemia-reperfusion
      by antisense-oligodeoxynucleotides directed at beta(1)-adrenoceptor mRNA.
AB  - Plasma catecholamine levels rise, and myocardial beta(1)-adrenoceptor (beta(1)
      AR) sensitivity increases during ischemia. These factors enhance myocardial
      injury and cardiac dysfunction. beta(1)-AR blockers are clinically used to
      protect heart against ischemia and to improve cardiac dysfunction in patients
      with ischemic heart disease, but these agents often cause intolerable side
      effects. To examine the potential cardioprotective effect of therapy with
      antisense-oligodeoxynucleotides directed at beta(1)-AR mRNA (beta(1)-AS-ODNs)
      during myocardial ischemia-reperfusion, Sprague-Dawley rats were treated with
      beta(1)-AS-ODNs or inverted-oligodeoxynucleotides (IN-ODNs), each 200 microg/rat.
      Hearts were excised, perfused, and subjected to global ischemia (30 min) followed
      by reperfusion (30 min). Other rats were given selective beta(1)-AR blocker
      atenolol (2 mg/kg) or saline before excising the hearts. Ischemia-reperfusion
      resulted in cardiac dysfunction, indicated by an increase in coronary perfusion
      pressure and left ventricular end-diastolic pressure and a decrease in developed
      left ventricular pressure, as well as evidence of lipid peroxidation in saline
      treated rats (all P <.05 versus control values). Administration of AS-ODNs or
      atenolol, but not IN-ODNs, protected hearts against functional deterioration and
      lipid peroxidation (P <.05 versus saline or IN-ODNs treatment). AS-ODNs therapy
      appeared to be equivalent to atenolol in these effects. Expression of beta(1)-AR
      protein as well as mRNA in the myocardium were markedly up-regulated after
      ischemia-reperfusion, and treatment with beta(1)-AS-ODNs, but not atenolol,
      decreased the rise in enhanced expression of beta(1)-AR. These observations imply
      that beta(1)-AS-ODNs can ameliorate cardiac dysfunction after ischemia
      reperfusion by reducing the expression of beta(1)-AR in the ischemic-reperfused
      myocardium.

PMID- 10900254
TI  - Prenatal exposure to a low concentration of carbon monoxide disrupts hippocampal
      long-term potentiation in rat offspring.
AB  - The aim of the present study was to investigate whether functional changes at CA3
      CA1 synapses in the hippocampus could underlie learning and memory deficits
      produced in rat offspring by a prenatal exposure model simulating the carbon
      monoxide (CO) exposure observed in human cigarette smokers. Electrophysiological
      endpoints, including long-term potentiation, were examined in 15- to 30-day-old
      male rats whose mothers were exposed, from day 0 to day 20 of gestation, to 150
      ppm of CO resulting in blood levels of carboxyhemoglobin comparable to those
      found in human cigarette smokers. Evoked field excitatory postsynaptic potentials
      were measured in the stratum radiatum in hippocampal slices. Results show that
      before tetanus, input/output functions, presynaptic volley, and paired-pulse
      facilitation were not affected in CO-exposed offspring, indicating that basal
      synaptic excitability and terminal Ca(2+) influx were not influenced by prenatal
      exposure to this gas. Conversely, evoked field excitatory postsynaptic potentials
      potentiation in response to tetanization was reduced by about 23% and decayed
      rapidly to baseline values in slices from CO-exposed animals. No changes between
      and within groups were observed in paired-pulse facilitation after tetanus. The
      selective impairment of long-term potentiation expression exhibited by CO-exposed
      rats was paralleled by a significant decrease in heme-oxygenase 2 and neuronal
      nitric-oxide synthase in the hippocampus. No changes in either enzymatic activity
      were found in frontal cortex and cerebellum. These electrophysiological and
      biochemical alterations might account for cognitive deficits previously observed
      in rats exposed prenatally to CO. Our findings could have clinical implications
      for the offspring of mothers who smoke during pregnancy.

PMID- 10900255
TI  - Disposition of glutathione conjugates in rats by a novel glutamic acid pathway:
      characterization of unique peptide conjugates by liquid chromatography/mass
      spectrometry and liquid chromatography/NMR.
AB  - With the advent of liquid chromatography/mass spectrometry and liquid
      chromatography/NMR, it has become easier to characterize metabolites that were
      once difficult to isolate and identify. These techniques have enabled us to
      uncover the existence of an alternate pathway for the disposition of glutathione
      adducts of several structurally diverse compounds. Studies were carried out using
      acetaminophen as a model compound to investigate the role of the glutamic acid
      pathway in disposition of the glutathione adducts. Although the mercapturic acid
      pathway was the major route of degradation of the glutathione adducts, it was
      found that the conjugation of the glutathione, cysteinylglycine, and cysteine
      adducts of acetaminophen with the gamma-carboxylic acid of the glutamic acid was
      both interesting and novel. The coupling of the glutathione adduct and the
      products from the mercapturic acid pathway with the glutamic acid led to unusual
      peptide conjugates. The natures of these adducts were confirmed unequivocally by
      comparisons with synthetic standards. This pathway (addition of glutamic acids)
      led to larger peptides, in contrast to the mercapturic acid pathway, in which the
      glutathione adducts are broken down to smaller molecules. The enzyme responsible
      for the addition of glutamic acid to the different elements of the mercapturic
      acid pathway is currently unknown. It is postulated that the gamma-carboxylic
      acid is activated (perhaps by ATP) before enzymatic addition to the alpha-amino
      group of cysteine or glutamate takes place. The discovery of these peptide
      conjugates of acetaminophen represents a novel disposition of glutathione adducts
      of compounds. The formation of such conjugates may represent yet another pathway
      by which drugs could produce covalent binding via their reactive intermediates.

PMID- 10900257
TI  - Bioactivation of selenocysteine Se-conjugates by a highly purified rat renal
      cysteine conjugate beta-lyase/glutamine transaminase K.
AB  - Selenocysteine Se-conjugates have recently been proposed as potential prodrugs to
      target pharmacologically active selenol compounds to the kidney. Although rat
      renal cytosol displayed a high activity of beta-elimination activity toward these
      substrates, the enzymes involved in this activation pathway as yet have not been
      identified. In the present study, the possible involvement of cysteine conjugate
      beta-lyase/glutamine transaminase K (beta-lyase/GTK) in cytosolic activity was
      investigated. To this end, the enzyme kinetics of 15 differentially substituted
      selenocysteine Se-conjugates and 11 cysteine S-conjugates was determined using
      highly purified rat renal beta-lyase/GTK. The results demonstrate that most
      selenocysteine Se-conjugates are beta-eliminated at a very high activity by
      purified beta-lyase/GTK, implicating an important role of this protein in the
      previously reported beta-elimination reactions in rat renal cytosol. As indicated
      by the rapid consumption of alpha-keto-gamma-methiolbutyric acid, purified beta
      lyase/GTK also catalyzed transamination reactions, which appeared to even exceed
      that of beta-elimination. The corresponding sulfur analogs also showed
      significant transamination but were beta-eliminated at an extremely low rate.
      Comparison of the obtained enzyme kinetic data of purified beta-lyase/GTK with
      previously obtained data from rat renal cytosol showed a poor correlation. By
      determining the activity profiles of cytosolic fractions applied to anion
      exchange fast protein liquid chromatography and gel filtration chromatography,
      the involvement of multiple enzymes in the beta-elimination of selenocysteine Se
      conjugates in rat renal cytosol was demonstrated. The identity and
      characteristics of these alternative selenocysteine conjugate beta-lyases,
      however, remain to be established.

PMID- 10900256
TI  - Chronopharmacology of antitumor effect induced by interferon-beta in tumor
      bearing mice.
AB  - The mechanisms underlying the dosing time-dependent change in the antitumor
      effect of interferon-beta (IFN-beta) were investigated based on the sensitivity
      of tumor cells and the pharmacokinetics of the drug. Tumor-bearing mice were
      housed under standardized light-dark cycle conditions (lights on at 7:00 AM, off
      at 7:00 PM) with food and water available ad libitum. The antitumor effect of IFN
      beta (0.5 MI.U./kg, intratumoral) was more efficient in early light phase than in
      early dark phase. The higher antitumor effect of IFN-beta was observed when
      specific binding of IFN receptor and DNA synthesis in tumor cells increased, and
      the lower effect was observed when these levels decreased. The dosing time
      dependent effect of IFN-beta was supported by the time-dependent expression of
      transcription factor (signal transducers and activators of transcription 1) and
      cell proliferation inhibitor (p21 wild-type p53-activated fragment 1) protein
      induced by IFN-beta. There was a significant dosing time-dependent change in IFN
      beta concentration in tumor, with a higher level in early light phase and a lower
      level in early dark phase. The dosing time-dependent change of IFN-beta
      concentration in tumor was associated with that of IFN-beta-induced antitumor
      effect. These results suggest that by choosing the most suitable dosing time for
      IFN-beta, the efficacy of the drug can be increased in certain experimental and
      clinical situations.

PMID- 10900258
TI  - Evaluation of the kinetics of beta-elimination reactions of selenocysteine Se
      conjugates in human renal cytosol: possible implications for the use as kidney
      selective prodrugs.
AB  - This study was performed to evaluate whether selenocysteine Se-conjugates are
      substrates for human cysteine conjugate beta-lyase enzymes. By testing kidney
      cytosols of three different humans, we studied interindividual differences in
      beta-lyase enzymes in humans. A series of 22 selenocysteine Se-conjugates were
      tested in rat and human kidney cytosols to compare their ability to form selenol
      compounds by beta-elimination. All compounds appeared to be good substrates for
      rat and human cysteine conjugate beta-lyase enzymes. The beta-lyase activity
      toward the selenocysteine Se-conjugates was comparable with those of the known
      nephrotoxic cysteine S-conjugate S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine in
      rats and humans. In rat kidney cytosol, between 22- and 877-fold higher beta
      elimination rates were observed compared with human kidney cytosol. Significant
      correlations (P <.0001) between three human kidney cytosols in beta-lyase
      activities were found within the tested series of 22 compounds. Specific beta
      lyase activities and intrinsic clearances of beta-elimination reactions ranged up
      to 3-fold, indicating that there are quantitative rather than qualitative
      interindividual differences in beta-eliminating enzymes in humans. Furthermore,
      Se-alkyl selenocysteine conjugates showed a sterically dependent bioactivation to
      selenol compounds in humans but not in rats. The present study supports the
      hypothesis that selenocysteine Se-conjugates may be useful as prodrugs to target
      pharmacologically active selenol compounds (e.g., antitumor or chemoprotective)
      to the kidney in humans.

PMID- 10900259
TI  - Inhibition of alpha(1)-adrenergic-mediated responses in rat ventricular myocytes
      by adenosine A(1) receptor activation: role of the K(ATP) channel.
AB  - Both beta- and alpha(1)-adrenoceptors mediate the myocardial effects of
      catecholamines. It is well known that adenosine inhibits beta-dependent effects;
      however, whether alpha(1)-dependent responses can be similarly modulated is
      unclear. Accordingly, rat ventricular myocytes were exposed for 25 min to the
      alpha(1) agonist phenylephrine (2 microM, in the presence of 1 microM
      propranolol) in the absence or presence of adenosine (100 microM) or the A(1)
      receptor-selective agonist N(6)-cyclopentyladenosine (CPA, 1 microM). We also
      investigated the effects of K(ATP) blockade with glibenclamide (1 microM), the
      protein kinase C inhibitor bisindolylmaleimide (20 nM), and pertussis toxin (300
      ng/ml), which uncouples G(i) protein/receptor interaction, and assessed whether
      effects of adenosine were mimicked by K(ATP) activation with either pinacidil or
      cromakalim (5 microM). Phenylephrine significantly increased cell shortening by
      190% and the Ca(2+) transient by 24%, which was abolished by either adenosine or
      CPA, but not in the presence of the A(1) receptor-selective antagonist 8
      cyclopentyl-1, 3-dipropylxanthine (1 microM), and was abolished by pertussis
      toxin. The effect of adenosine or CPA was reversed by glibenclamide and mimicked
      by either cromakalim or pinacidil. Bisindolylmaleimide was without effect. The
      A(2) or A(3) receptor agonists 2-(4-(2-carboxyethyl)phenylethylamino)-5'-N
      ethylcarboxamidoade nos ine and N(6)-(3-iodobenzyl)-adenosine-5'-N
      methyluronamide (1 microM each), respectively, were without effect. Neither CPA
      nor adenosine modulated the effect of endothelin-1 (5 nM), which also acts via
      the phosphoinositide hydrolysis pathway. We conclude that adenosine selectively
      inhibits alpha(1)-adrenergic-mediated effects in rat ventricular myocytes through
      a G(i) protein-dependent mechanism involving A(1) receptor and K(ATP) activation.
      Our study further suggests that endogenous adenosine may modulate alpha(1)
      mediated effects of catecholamines.

PMID- 10900260
TI  - Effect of cyclosporine on HMG-CoA reductase, cholesterol 7alpha-hydroxylase, LDL
      receptor, HDL receptor, VLDL receptor, and lipoprotein lipase expressions.
AB  - Long-term administration of cyclosporine (CsA) has been shown to cause
      hypercholesteremia, hypertriglyceridemia, and elevations of plasma low-density
      and very low-density lipoprotein (LDL and VLDL) levels in humans. This study was
      undertaken to explore the effects of CsA on expressions of the key lipid
      regulatory enzymes and receptors. Thus, hepatic expressions of cholesterol 7alpha
      hydroxylase (the rate-limiting step in cholesterol conversion to bile acids), LDL
      receptor, and high-density lipoprotein (HDL) receptor proteins, as well as 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity were determined
      in rats treated with CsA (18 mg/kg/day) or placebo for 3 weeks. In addition,
      skeletal muscle and adipose tissue expressions of lipoprotein lipase and VLDL
      receptor were measured. Western blot analysis was used for all protein
      measurements using appropriate antibodies against the respective proteins. CsA
      treated animals showed mild but significant elevations of plasma cholesterol and
      triglyceride concentrations. This was associated with a marked down-regulation of
      cholesterol 7alpha-hydroxylase in the liver and a severe reduction of lipoprotein
      lipase abundance in skeletal muscle and adipose tissue. However, hepatic LDL
      receptor and HDL receptor expressions and HMG-CoA reductase activity were not
      altered by CsA therapy. Likewise, skeletal muscle and adipose tissue VLDL
      receptor protein expressions were unaffected by CsA administration under the
      given condition. In conclusion, CsA administration for 3 weeks resulted in a
      significant reduction of hepatic cholesterol 7alpha-hydroxylase and marked down
      regulation of skeletal muscle and adipose tissue lipoprotein lipase abundance in
      rats. The former abnormality can contribute to hypercholesterolemia by limiting
      cholesterol catabolism, whereas the latter may contribute to hypertriglyceridemia
      and VLDL accumulation by limiting triglyceride-rich lipoprotein clearance in CsA
      treated animals.

PMID- 10900261
TI  - Intra-ventral tegmental area injection of rat cocaine and amphetamine-regulated
      transcript peptide 55-102 induces locomotor activity and promotes conditioned
      place preference.
AB  - Cocaine- and amphetamine-regulated transcript (CART) is a novel mRNA that has
      been reported to be increased by acute psychostimulant administration, and that
      may be involved in the effects of psychostimulants. In this study, we examined
      the effect of centrally administered CART peptides on locomotor activity and
      conditioned place preference in the rat. CART peptide fragments were bilaterally
      injected into the ventral tegmental area. CART 55-102 (0.2-5.0 microg/side), an
      endogenously occurring peptide, dose dependently increased locomotor activity,
      whereas CART 1-26 (0.1-2.5 microg/side; not found endogenously) did not. The
      locomotor effects of CART 55-102 were dose dependently blocked by the dopamine
      D(2) receptor antagonist haloperidol (0.03-1.0 mg/kg i.p.). Four injections of
      1.0 microg/side CART 55-102 induced a significant place preference, suggesting
      that CART 55-102 is reinforcing. Increases in locomotor activity after each of
      these CART 55-102 injections were similar and did not show tolerance or
      sensitization. This treatment regimen of CART 55-102 also did not produce
      sensitization to locomotor activity after a subsequent challenge with cocaine or
      amphetamine. When CART 55-102 (0.2-1.0 microg/side) was injected into the
      substantia nigra, no significant change in motor activity was observed. However,
      a higher dose of CART 55-102 (5.0 microg/side) induced a delayed increase in
      motor activity, suggesting a possible diffusion from the substantia nigra into
      the ventral tegmental area. Our findings suggest that CART 55-102 is behaviorally
      active and may be involved in the actions of psychostimulants. This is the first
      demonstration of the psychostimulant-like effects of CART peptides.

PMID- 10900262
TI  - Inhibition of growth and metastatic progression of pancreatic carcinoma in
      hamster after somatostatin receptor subtype 2 (sst2) gene expression and
      administration of cytotoxic somatostatin analog AN-238.
AB  - The sst2 somatostatin receptor mediates the antiproliferative effects of
      somatostatin analogs. The present study demonstrates that stable expression of
      sst2 in the hamster pancreatic cancer cells PC-1 and PC-1.0 activates an
      autocrine negative loop leading to an in vitro inhibition of cell proliferation.
      In vivo studies conducted in Syrian golden hamsters after orthotopic implantation
      of PC-1.0 cells showed that both tumor growth and metastatic progression of
      allografts containing 100% of sst2-expressing cells were significantly inhibited
      for up to 20 days after implantation, as compared with control allografts that
      did not express sst2. A local antitumor bystander effect was observed after
      induction of mixed tumors containing a 1:3 ratio of sst2-expressing cells to
      control cells. Tumor volume and incidence of metastases of mixed tumors were
      significantly reduced at day 13 post implantation. This effect decreased with
      time as at day 20, growth of mixed tumors was similar to that of control tumors.
      After administration of the cytotoxic somatostatin conjugate AN-238 on day 13,
      antitumor bystander effect observed in mixed tumors was significantly extended to
      day 20. We also observed that in vitro invasiveness of sst2-expressing PC-1.0
      cells was significantly reduced. Tyrosine dephosphorylation of E-cadherin may
      participate in restoring the E-cadherin function, reducing in turn pancreatic
      cancer cell motility and invasiveness. This dephosphorylation depends on the
      tyrosine phosphatase src homology 2-containing tyrosine phosphatase 1 (SHP-1)
      positively coupled to sst2 receptor. The inhibitory effect of sst2 gene
      expression on pancreatic cancer growth and invasion combined with chemotherapy
      with targeted cytotoxic somatostatin analog administration provides a rationale
      for a therapeutic approach to gene therapy based on in vivo sst2 gene transfer.

PMID- 10900263
TI  - Normotonic cell shrinkage because of disordered volume regulation is an early
      prerequisite to apoptosis.
AB  - A major hallmark of apoptosis is normotonic shrinkage of cells. Here, we studied
      the relation between apoptotic cell shrinkage and apoptotic cell death. Induction
      of the apoptotic volume decrease (AVD) under normotonic conditions was found to
      be coupled to facilitation of the regulatory volume decrease (RVD), which is
      known to be attained by parallel operation of Cl(-) and K(+) channels, under
      hypotonic conditions. Both the AVD induction and the RVD facilitation were found
      to precede cytochrome c release, caspase-3 activation, DNA laddering, and
      ultrastructural alterations in three cell types after apoptotic insults with two
      distinct apoptosis inducers. Also, the AVD was not prevented by a broad-spectrum
      caspase inhibitor. When the AVD induction and the RVD facilitation were prevented
      by blocking volume-regulatory Cl(-) or K(+) channels, these cells did not show
      succeeding apoptotic biochemical and morphological events and were rescued from
      death. Thus, it is concluded that the AVD, which is caused by disordered cell
      volume regulation, is an early prerequisite to apoptotic events leading to cell
      death.

PMID- 10900264
TI  - The Arabidopsis dnd1 "defense, no death" gene encodes a mutated cyclic nucleotide
      gated ion channel.
AB  - Gene-for-gene disease resistance typically includes a programmed cell death
      response known as the hypersensitive response (HR). The Arabidopsis thaliana dnd1
      mutant was previously isolated as a line that failed to produce the HR in
      response to avirulent Pseudomonas syringae pathogens; plants homozygous for the
      recessive dnd1-1 mutation still carry out effective gene-for-gene resistance. The
      dnd1-1 mutation also causes constitutive systemic resistance and elevated levels
      of salicylic acid. In the present study, a positional cloning approach was used
      to isolate DND1. DND1 encodes the same protein as AtCNGC2, a cyclic nucleotide
      gated ion channel of previously unknown organismal function that can allow
      passage of Ca(2+), K(+) and other cations [Leng, Q., Mercier, R. W., Yao, W. &
      Berkowitz, G. A. (1999) Plant Physiol. 121, 753-761]. By using a nahG transgene,
      we found that salicylic acid is required for the elevated resistance caused by
      the dnd1 mutation but that removal of salicylic acid did not completely eliminate
      the dwarf and loss-of-HR phenotypes of mutant dnd1 plants. A stop codon that
      would severely truncate the DND1 gene product was identified in the dnd1-1
      allele. This demonstrates that broad-spectrum disease resistance and inhibition
      of the HR can be activated in plants by disruption of a cyclic nucleotide-gated
      ion channel.

PMID- 10900265
TI  - Redesign of substrate-selectivity determining modules of glutathione transferase
      A1-1 installs high catalytic efficiency with toxic alkenal products of lipid
      peroxidation.
AB  - The evolution of proteins for novel functions involves point mutations and
      recombinations of domains or structural segments. Mimicking this process by
      rational design in vitro is still a major challenge. The present report
      demonstrates that the active site of the enzyme glutathione transferase (GST) A1
      1 can be tailored for high catalytic efficiency with alkenals. The result is a
      >3,000-fold change in substrate selectivity involving a noteworthy change in
      preferred catalyzed reaction from aromatic nucleophilic substitution to Michael
      addition. The hydrophobic substrate binding pocket of GST A1-1 is formed by three
      structural modules, which were redesigned sequentially with four point mutations
      and the exchange of a helical segment. The substitutions were made to mimic first
      sphere interactions with a substrate in GST A4-4, which naturally has high
      activity with alkenals. These substrates are toxic lipid peroxidation products of
      pathophysiological significance, and glutathione conjugation is a route of their
      inactivation. The final product of the sequential redesign of GST A1-1, mutant
      GIMFhelix, had a 300-fold increase in catalytic efficiency with nonenal and a >10
      times decreased activity with 1-chloro-2,4-dinitrobenzene. In absolute values,
      GIMFhelix is more efficient than wild-type GST A4-4 with some alkenal substrates,
      with a k(cat)/K(m) value of 1.5 +/- 0. 1 10(6) M(-1) small middle dots(-1) for
      nonenal. The pKa value of the active-site Tyr-9 of GIMFhelix is 7.3 +/- 0.1,
      approaching the unusually low value of GST A4-4. Thus, rational redesign of the
      active-site region of an enzyme may be sufficient for the generation of efficient
      catalysts with altered chemical mechanism and novel selectivity.

PMID- 10900266
TI  - Transcription-coupled repair in yeast is independent from ubiquitylation of RNA
      pol II: implications for Cockayne's syndrome.
AB  - Cockayne's syndrome cells lack transcription-coupled nucleotide excision repair
      (TCR) and ubiquitylation of RNA polymerase II large subunit (RNA pol II LS),
      suggesting that ubiquitylation of RNA pol II LS may be necessary for TCR in
      eukaryotes. Rsp5 is the sole yeast ubiquitin-protein ligase that ubiquitylates
      RNA pol II LS in cells exposed to DNA-damaging agents. In yeast lacking
      functional Rsp5, there is no ubiquitylation of RNA pol II LS. We show here that
      removal, repression, or over-expression of Rsp5 has no effect on TCR,
      demonstrating that ubiquitylation of the RNA pol II LS is not required for TCR.
      We infer that the lack of ubiquitylation of RNA pol II LS in Cockayne's syndrome
      cells does not cause their defect in TCR.

PMID- 10900267
TI  - The spliceosomal snRNP core complex of Trypanosoma brucei: cloning and functional
      analysis reveals seven Sm protein constituents.
AB  - Each of the trypanosome small nuclear ribonucleoproteins (snRNPs) U2, U4/U6, and
      U5, as well as the spliced leader (SL) RNP, contains a core of common proteins,
      which we have previously identified. This core is unusual because it is not
      recognized by anti-Sm Abs and it associates with an Sm-related sequence in the
      trypanosome small nuclear RNAs (snRNAs). Using peptide sequences derived from
      affinity-purified U2 snRNP proteins, we have cloned cDNAs for five common
      proteins of 8.5, 10, 12.5, 14, and 15 kDa of Trypanosoma brucei and identified
      them as Sm proteins SmF (8.5 kDa), -E (10 kDa), -D1 (12.5 kDa), -G (14 kDa), and 
      D2 (15 kDa), respectively. Furthermore, we found the trypanosome SmB (T. brucei)
      and SmD3 (Trypanosoma cruzi) homologues through database searches, thus
      completing a set of seven canonical Sm proteins. Sequence comparisons of the
      trypanosome proteins revealed several deviations in highly conserved positions
      from the Sm consensus motif. We have identified a network of specific
      heterodimeric and -trimeric Sm protein interactions in vitro. These results are
      summarized in a model of the trypanosome Sm core, which argues for a strong
      conservation of the Sm particle structure. The conservation extends also to the
      functional level, because at least one trypanosome Sm protein, SmG, was able to
      specifically complement a corresponding mutation in yeast.

PMID- 10900268
TI  - In vitro and in vivo evidence for orphan nuclear receptor RORalpha function in
      bone metabolism.
AB  - Bone is a major target site for steroid hormone action. Steroid hormones like
      cortisol, vitamin D, and estradiol are responsible for principal events
      associated with bone formation and resorption. Over the past decade, new members
      of the nuclear hormone gene family have been identified that lack known ligands.
      These orphan receptors can be used to uncover signaling molecules that regulate
      yet unidentified physiological networks. In the present study the function of
      retinoic acid receptor-related orphan receptor (ROR) alpha in bone metabolism has
      been examined. We showed that RORalpha and RORgamma, but not RORbeta, are
      expressed in mesenchymal stem cells derived from bone marrow. Interestingly, for
      RORalpha we observed an increased messenger signal expression between control
      cells and cells undergoing osteogenic differentiation. Furthermore, the direct
      activation of mouse bone sialoprotein by RORalpha, typically 7-fold, has been
      shown. In contrast, transient overexpression of RORalpha overrides the activation
      of the osteocalcin promoter by 1alpha,25-dihydroxyvitamin D(3). In addition, we
      have investigated bone mass parameters and bone geometry in the mouse mutant
      staggerer (sg/sg), a mouse strain that carries a deletion within the RORalpha
      gene. Homozygote mutants have thin long bones compared with the heterozygote
      animals and wild-type littermates. More interestingly, the bones of the sg/sg
      animals are osteopenic as indicated by the comparison of bone mineral contents of
      sg/sg animals to the heterozygote and wild-type animals. We conclude that these
      in vitro and in vivo results suggest a function for RORalpha in bone biology.
      RORalpha most likely acts by direct modulation of a bone matrix component.

PMID- 10900269
TI  - High-frequency intrachromosomal gene conversion induced by triplex-forming
      oligonucleotides microinjected into mouse cells.
AB  - To test the ability of triple helix-forming oligonucleotides (TFOs) to promote
      recombination within chromosomal sites in mammalian cells, a mouse LTK(-) cell
      line was established carrying two mutant copies of the herpes simplex virus
      thymidine kinase (TK) gene as direct repeats in a single chromosomal locus.
      Recombination between these repeats can produce a functional TK gene and occurs
      at a spontaneous frequency of 4 x 10(-6) under standard culture conditions. When
      cells were microinjected with TFOs designed to bind to a 30-bp polypurine site
      situated between the two TK genes, recombination was observed at frequencies in
      the range of 1%, 2,500-fold above the background. Recombination was induced
      efficiently by injection of both psoralen-conjugated TFOs (followed by long-wave
      UVA light; 1. 2%) and unconjugated TFOs alone (1.0%). Control oligomers of
      scrambled sequence but identical base composition were ineffective, and no TFO
      induced recombination was seen in a control LTK(-) cell line carrying an
      otherwise identical dual TK gene construct lacking the 30-bp polypurine target
      site. TFOs transfected with cationic lipids also induced recombinants in a highly
      sequence-specific manner but were less effective, with induced recombination
      frequencies of 6- to 7-fold over background. Examination of the TFO-induced
      recombinants by genomic Southern blotting revealed gene conversion events in
      which both TK genes were retained, but either the upstream (57%) or the
      downstream gene (43%) was corrected to wild type. These results suggest that,
      with efficient intracellular delivery, TFOs may be effective tools to promote
      site-specific recombination and targeted modification of chromosomal loci.

PMID- 10900270
TI  - New roles for cis-jasmone as an insect semiochemical and in plant defense.
AB  - cis-jasmone, or (Z)-jasmone, is well known as a component of plant volatiles, and
      its release can be induced by damage, for example during insect herbivory. Using
      the olfactory system of the lettuce aphid to investigate volatiles from plants
      avoided by this insect, (Z)-jasmone was found to be electrophysiologically active
      and also to be repellent in laboratory choice tests. In field studies, repellency
      from traps was demonstrated for the damson-hop aphid, and with cereal aphids
      numbers were reduced in plots of winter wheat treated with (Z)-jasmone. In
      contrast, attractant activity was found in laboratory and wind tunnel tests for
      insects acting antagonistically to aphids, namely the seven-spot ladybird and an
      aphid parasitoid. When applied in the vapor phase to intact bean plants, (Z)
      jasmone induced the production of volatile compounds, including the monoterpene
      (E)-beta-ocimene, which affect plant defense, for example by stimulating the
      activity of parasitic insects. These plants were more attractive to the aphid
      parasitoid in the wind tunnel when tested 48 h after exposure to (Z)-jasmone had
      ceased. This possible signaling role of (Z)-jasmone is qualitatively different
      from that of the biosynthetically related methyl jasmonate and gives a long
      lasting effect after removal of the stimulus. Differential display was used to
      compare mRNA populations in bean leaves exposed to the vapor of (Z)-jasmone and
      methyl jasmonate. One differentially displayed fragment was cloned and shown by
      Northern blotting to be up-regulated in leaf tissue by (Z)-jasmone. This sequence
      was identified by homology as being derived from a gene encoding an alpha-tubulin
      isoform.

PMID- 10900271
TI  - Myotubularin, a protein tyrosine phosphatase mutated in myotubular myopathy,
      dephosphorylates the lipid second messenger, phosphatidylinositol 3-phosphate.
AB  - The lipid second messenger phosphatidylinositol 3-phosphate [PI(3)P] plays a
      crucial role in intracellular membrane trafficking. We report here that
      myotubularin, a protein tyrosine phosphatase required for muscle cell
      differentiation, is a potent PI(3)P phosphatase. Recombinant human myotubularin
      specifically dephosphorylates PI(3)P in vitro. Overexpression of a catalytically
      inactive substrate-trapping myotubularin mutant (C375S) in human 293 cells
      increases PI(3)P levels relative to that of cells overexpressing the wild-type
      enzyme, demonstrating that PI(3)P is a substrate for myotubularin in vivo. In
      addition, a Saccharomyces cerevisiae strain in which the myotubularin-like gene
      (YJR110w) is disrupted also exhibits increased PI(3)P levels. Both the
      recombinant yeast enzyme and a human myotubularin-related protein (KIAA0371) are
      able to dephosphorylate PI(3)P in vitro, suggesting that this activity is
      intrinsic to all myotubularin family members. Mutations in the MTM1 gene that
      cause human myotubular myopathy dramatically reduce the ability of the
      phosphatase to dephosphorylate PI(3)P. Our findings provide evidence that
      myotubularin exerts its effects during myogenesis by regulating cellular levels
      of the inositol lipid PI(3)P.

PMID- 10900273
TI  - The role of dynamic palmitoylation in Ca2+ channel inactivation.
AB  - N- and P/Q-type Ca(2+) channels regulate a number of critical physiological
      processes including synaptic transmission and hormone secretion. These Ca(2+)
      channels are multisubunit proteins, consisting of a pore-forming alpha(1), and
      accessory beta and alpha(2)delta subunits each encoded by multiple genes and
      splice variants. beta subunits alter current amplitude and kinetics. The beta(2a)
      subunit is associated with slowed inactivation, an effect that requires the
      palmitoylation of two N-terminal cysteine residues in beta(2a). In the current
      manuscript, we studied steady state inactivation properties of native N- and P/Q
      type Ca(2+) channels and recombinant N-type Ca(2+) channels. When bovine
      alpha(1B) and beta(2a) and human alpha(2)delta were coexpressed in tsA 201 cells,
      we observed significant variations in inactivation; some cells exhibited
      virtually no inactivation as the holding potential was altered whereas others
      exhibited significant inactivation. A similar variability in inactivation was
      observed in native channels from bovine chromaffin cells. In individual
      chromaffin cells, the amount of inactivation exhibited by N-type channels was
      correlated with the inactivation of P/Q-type channels, suggesting a shared
      mechanism. Our results with recombinant channels with known beta subunit
      composition indicated that inactivation could be dynamically regulated, possibly
      by alterations in beta subunit palmitoylation. Tunicamycin, which inhibits
      palmitoylation, increased steady-state inactivation of Ca(2+) channels in
      chromaffin cells. Cerulenin, another drug that inhibits palmitoylation, also
      increased inactivation. Tunicamycin produced a similar effect on recombinant N
      type Ca(2+) channels containing beta(2a) but not beta(2b) or beta(2a) subunits
      mutated to be palmitoylation deficient. Our results suggest that Ca(2+) channels
      containing beta(2a) subunits may be regulated by dynamic palmitoylation.

PMID- 10900274
TI  - Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans
      Affairs Cooperative Study Group 380.
AB  - BACKGROUND AND METHODS: The role of colonoscopy in screening for colorectal
      cancer is uncertain. At 13 Veterans Affairs Medical Centers, we performed
      colonoscopy to determine the prevalence and location of advanced colonic
      neoplasms and the risk of advanced proximal neoplasia in asymptomatic patients
      (age range, 50 to 75 years) with or without distal neoplasia. Advanced colonic
      neoplasia was defined as an adenoma that was 10 mm or more in diameter, a villous
      adenoma, an adenoma with high-grade dysplasia, or invasive cancer. In patients
      with more than one neoplastic lesion, classification was based on the most
      advanced lesion. RESULTS: Of 17,732 patients screened for enrollment, 3196 were
      enrolled; 3121 of the enrolled patients (97.7 percent) underwent complete
      examination of the colon. The mean age of the patients was 62.9 years, and 96.8
      percent were men. Colonoscopic examination showed one or more neoplastic lesions
      in 37.5 percent of the patients, an adenoma with a diameter of at least 10 mm or
      a villous adenoma in 7.9 percent, an adenoma with high-grade dysplasia in 1.6
      percent, and invasive cancer in 1.0 percent. Of the 1765 patients with no polyps
      in the portion of the colon that was distal to the splenic flexure, 48 (2.7
      percent) had advanced proximal neoplasms. Patients with large adenomas (> or = 10
      mm) or small adenomas (< 10 mm) in the distal colon were more likely to have
      advanced proximal neoplasia than were patients with no distal adenomas (odds
      ratios, 3.4 [95 percent confidence interval, 1.8 to 6.5] and 2.6 (95 percent
      confidence interval, 1.7 to 4.1], respectively). However, 52 percent of the 128
      patients with advanced proximal neoplasia had no distal adenomas. CONCLUSIONS:
      Colonoscopic screening can detect advanced colonic neoplasms in asymptomatic
      adults. Many of these neoplasms would not be detected with sigmoidoscopy.

PMID- 10900275
TI  - Risk of advanced proximal neoplasms in asymptomatic adults according to the
      distal colorectal findings.
AB  - BACKGROUND AND METHODS: The clinical significance of a distal colorectal polyp is
      uncertain. We determined the risk of advanced proximal neoplasia, defined as a
      polyp with villous features, a polyp with high-grade dysplasia, or cancer, among
      persons with distal hyperplastic or neoplastic polyps as compared with the risk
      among persons with no distal polyps. We analyzed data from 1994 consecutive
      asymptomatic adults (age, 50 years or older) who underwent colonoscopic screening
      for the first time between September 1995 and December 1998 as part of a program
      sponsored by an employer. The location and histologic features of all polyps were
      recorded. Colonoscopy to the level of the cecum was completed in 97.0 percent of
      the patients. RESULTS: Sixty-one patients (3.1 percent) had advanced lesions in
      the distal colon, including 5 with cancer, and 50 (2.5 percent) had advanced
      proximal lesions, including 7 with cancer. Twenty-three patients with advanced
      proximal neoplasms (46 percent) had no distal polyps. The prevalence of advanced
      proximal neoplasia among patients with no distal polyps was 1.5 percent (23 cases
      among 1564 persons; 95 percent confidence interval, 0.9 to 2.1 percent). Among
      patients with distal hyperplastic polyps, those with distal tubular adenomas, and
      those with advanced distal polyps, the prevalence of advanced proximal neoplasia
      was 4.0 percent (8 cases among 201 patients), 7.1 percent (12 cases among 168
      patients), and 11.5 percent (7 cases among 61 patients), respectively. The
      relative risk of advanced proximal neoplasia, adjusted for age and sex, was 2.6
      for patients with distal hyperplastic polyps, 4.0 for those with distal tubular
      adenomas, and 6.7 for those with advanced distal polyps, as compared with
      patients who had no distal polyps. Older age and male sex were associated with an
      increased risk of advanced proximal neoplasia (relative risk, 1.3 for every five
      years of age and 3.3 for male sex). CONCLUSIONS: Asymptomatic persons 50 years of
      age or older who have polyps in the distal colon are more likely to have advanced
      proximal neoplasia than are persons without distal polyps. However, if
      colonoscopic screening is performed only in persons with distal polyps, about
      half the cases of advanced proximal neoplasia will not be detected.

PMID- 10900276
TI  - Rapid detection of group B streptococci in pregnant women at delivery.
AB  - BACKGROUND: Group B streptococcal infections are an important cause of neonatal
      morbidity and mortality. A rapid method for the detection of this organism in
      pregnant women at the time of delivery is needed to allow early treatment of
      neonates. METHODS: We studied the efficacy of two polymerase-chain-reaction (PCR)
      assays for routine screening of pregnant women for group B streptococci at the
      time of delivery. We obtained anal, vaginal, and combined vaginal and anal
      specimens from 112 pregnant women; in 57 women, specimens were obtained before
      and after the rupture of the amniotic membranes. The specimens were tested for
      group B streptococci by culture in a standard selective broth medium, with a
      conventional PCR assay, and with a new fluorogenic PCR assay. RESULTS: Among the
      112 women, the results of the culture of the combined vaginal and anal specimens
      were positive for group B streptococci in 33 women (29.5 percent). The two PCR
      assays detected group B streptococcal colonization in specimens from 32 of these
      33 women: the one negative PCR result was in a sample obtained after the rupture
      of membranes. As compared with the culture results, the sensitivity of both PCR
      assays was 97.0 percent and the negative predictive value was 98.8 percent. Both
      the specificity and the positive predictive value of the two PCR assays were 100
      percent. The length of time required to obtain results was 30 to 45 minutes for
      the new PCR assay, 100 minutes for the conventional PCR assay, and at least 36
      hours for culture. CONCLUSIONS: Colonization with group B streptococci can be
      identified rapidly and reliably by a PCR assay in pregnant women in labor both
      before and after the rupture of membranes.

PMID- 10900277
TI  - Prevention of radiographic-contrast-agent-induced reductions in renal function by
      acetylcysteine.
AB  - BACKGROUND: Radiographic contrast agents can cause a reduction in renal function
      that may be due to reactive oxygen species. Whether the reduction can be
      prevented by the administration of antioxidants is unknown. METHODS: We
      prospectively studied 83 patients with chronic renal insufficiency (mean [+/-SD]
      serum creatinine concentration, 2.4+/-1.3 mg per deciliter [216+/-116 micromol
      per liter]) who were undergoing computed tomography with a nonionic, low
      osmolality contrast agent. Patients were randomly assigned either to receive the
      antioxidant acetylcysteine (600 mg orally twice daily) and 0.45 percent saline
      intravenously, before and after administration of the contrast agent, or to
      receive placebo and saline. RESULTS: Ten of the 83 patients (12 percent) had an
      increase of at least 0.5 mg per deciliter (44 micromol per liter) in the serum
      creatinine concentration 48 hours after administration of the contrast agent: 1
      of the 41 patients in the acetylcysteine group (2 percent) and 9 of the 42
      patients in the control group (21 percent; P=0.01; relative risk, 0.1; 95 percent
      confidence interval, 0.02 to 0.9). In the acetylcysteine group, the mean serum
      creatinine concentration decreased significantly (P<0.001), from 2.5+/-1.3 to
      2.1+/-1.3 mg per deciliter (220+/-118 to 186+/-112 micromol per liter) 48 hours
      after the administration of the contrast medium, whereas in the control group,
      the mean serum creatinine concentration increased nonsignificantly (P=0.18), from
      2.4+/-1.3 to 2.6+/-1.5 mg per deciliter (212+/-114 to 226+/-133 micromol per
      liter) (P<0.001 for the comparison between groups). CONCLUSIONS: Prophylactic
      oral administration of the antioxidant acetylcysteine, along with hydration,
      prevents the reduction in renal function induced by contrast agents in patients
      with chronic renal insufficiency.

PMID- 10900278
TI  - Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile
      hemangiomas.

PMID- 10900279
TI  - Images in clinical medicine. Boerhaave's syndrome.

PMID- 10900280
TI  - Reducing the risk of breast cancer.

PMID- 10900281
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 22-2000. A 74-year-old man with unrelenting dysphagia.

PMID- 10900282
TI  - Going the distance--the case for true colorectal-cancer screening.

PMID- 10900283
TI  - Neonatal group B streptococcal disease--screening and prevention.

PMID- 10900284
TI  - Acetylcysteine and nephrotoxic effects of radiographic contrast agents--a new use
      for an old drug.

PMID- 10900286
TI  - Correction: Hot-Tub Therapy for Type 2 Diabetes Mellitus.

PMID- 10900287
TI  - Correction: Role of Transforming Growth Factor (beta) in Human Disease.

PMID- 10900285
TI  - The case for more U.S. medical students.

PMID- 10900288
TI  - Effects of lisinopril and amlodipine on antioxidant status in experimental
      hypertension.
AB  - The objective of this investigation was to compare changes in antioxidant status
      (together with other metabolites relevant to hypertension) in plasma and cardiac
      tissue from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto
      rats (WKY), following 8 weeks of treatment with lisinopril (angiotensin
      converting enzyme inhibitor) or amlodipine (Ca(2+) channel antagonist)
      respectively. There was no significant difference in the levels of total
      antioxidant capacity, retinol, urea, albumin or triglyceride in plasma from SHR
      or WKY rats, with or without lisinopril or amlodipine treatment. However in SHR
      rats, levels of alpha-tocopherol were substantially reduced in both plasma (-54%
      WKY, P<0.01) and cardiac tissue (-43% WKY, P<0.05). Treatment with lisinopril
      ameliorated reduced levels of plasma alpha-tocopherol in SHR rats, but not in
      cardiac tissue. Amlodipine treatment had no effect on alpha-tocopherol levels in
      plasma or cardiac tissue in SHR rats. In SHR rats total cholesterol levels were
      significantly lower thanWKY controls (-36%, P<0.001). This effect was reversed in
      lisinopril treated SHR rats (+27%, P<0.01). Plasma high density lipoprotein (HDL)
      and low density lipoprotein (LDL) cholesterol were reduced in untreated SHR rats
      (P<0.025) when compared to WKY controls; neither lisinopril nor amlodipine
      treatment significantly altered these parameters. These findings suggest possible
      alternative mechanisms of action for lisinopril, and reinforce its use in
      hypertensive patients or patients with left ventricular hypertrophy.

PMID- 10900289
TI  - Gelatinase isoforms in urine from bladder cancer patients.
AB  - Matrix metalloproteinases are involved in tumor invasion and metastasis in many
      types of human carcinomas, in leukocyte infiltration and inflammatory reactions.
      Three metalloproteinases with gelatinolytic activity were isolated from the urine
      of patients with untreated high grade bladder cancer or with functioning renal
      grafts (control). Urinary proteins were fractionated after concentration by
      continuous-elution SDS-polyacrylamide gel electrophoresis. Collected fractions
      were analyzed by gelatin zymography and Western blotting. The one-step
      purification process isolated the gelatinase species from crude urine samples:
      (1) a 72 kDa progelatinase A (MMP-2) and its actived 68 kDa form; (2) a 92 kDa
      progelatinase B (MMP-9); (3) a higher molecular weight (HMW) complex (115 kDa)
      which was identified as progelatinase B associated with lipocalin, NGAL. A
      similar marker profile was observed in bladder cancer tissues. The current study
      demonstrated the efficiency of continuous elution electrophoresis. It offered two
      main advantages: (1) the separation of latent from active gelatinase isoforms
      with no interference from the TIMPs and (2) the identification and isolation in a
      single step of large amounts of urine gelatinase species with both high recovery
      and significant specific activities. Continuous-elution electrophoresis can be
      used for correlation with clinical events of bladder cancer diagnosis and
      prognosis.

PMID- 10900290
TI  - Synergistic effects in antigen capture ELISA using three monoclonal antibodies
      directed at different epitopes of the same antigen.
AB  - Using a panel of monoclonal antibodies (mAb) against human myoglobin (Mb), we
      have shown that the sensitivity of antigen-capture enzyme-linked immunosorbent
      assay (ELISA) may be significantly increased by the simultaneous immobilization
      on a solid phase of two co-operating capture mAbs. This method ("a three-site
      ELISA") uses three mAbs at different epitopes of the same antigen (two
      capture/one tracer), unlike the traditional two-site assay, using one capture and
      one tracer mAbs. We established two-site and three-site ELISA assays for Mb, by
      varying capture and tracer mAbs. Three-site assays showed 4-6 fold increase in
      sensitivity, if compared with two-site assays. The model for the effect has been
      suggested, according to which in three-site ELISA the high-affinity cyclic
      configurations may be formed by an antigen, two-capture mAbs and the surface of
      solid phase.

PMID- 10900291
TI  - A highly sensitive immuno-polymerase chain reaction assay for human
      angiotensinogen using the identical first and second polyclonal antibodies.
AB  - We describe an immuno-polymerase chain reaction (immuno-PCR) assay for the
      detection of human angiotensinogen using identical first and second polyclonal
      antibodies. The reporter DNA was initially generated by PCR amplification using a
      biotinylated primer, and was bound with streptavidin to biotinylated second
      antibody. Human recombinant angiotensinogen sandwiched by antibodies was detected
      by amplifying the reporter DNA using PCR. To reduce the effect of nonspecific
      amplification, the optimal concentrations of streptavidin and DNA label were
      determined to be 0.1 mg/l and 0.5 ng/l, respectively. The detection limit of the
      immuno-PCR assay was 0.1 ng/l, an approximately 2.5x10(5)-fold improvement
      compared with a conventional enzyme-linked immunosorbent assay. These results
      indicate that a highly sensitive immuno-PCR for human angiotensinogen can be
      developed even with identical first and second polyclonal antibodies.

PMID- 10900292
TI  - Activity and isoenzyme profile of N-acetyl-beta-D-glucosaminidase in urine from
      workers exposed to cadmium.
AB  - The urinary excretion of N-acetyl-beta-D-glucosaminidase (U-NAG) and urinary
      Cadmium (U-Cd) concentration, a measure of the metal load in the body, were
      evaluated in 28 workers exposed to Cd, to determine the relation between the two
      parameters. In urine from 22 exposed workers with U-Cd<2 microg/g creatinine (Cr)
      there was no significant difference in U-NAG value (0.98+/-0.59 U/gCr) compared
      to non-exposed (0.73+/-0.48 U/gCr). In the six workers with 2 microg/gCr < or =U
      Cd<10 microg/gCr the U-NAG (2.32+/-0.61 U/gCr) was statistically (P<0.05) higher
      than in other workers. In both the U-Cd intervals examined there were no altered
      values of beta2-microglobulin from urine of exposed workers compared to non
      exposed (<0.30 mg/l). The U-NAG isoenzymes were separated by DEAE-cellulose
      chromatography from urine of non-exposed subjects and exposed workers. The U-NAG
      isoenzyme profile in urine of non-exposed subjects showed a high percentage
      (about 95%) of the A (acid) form, a much lower percentage (about 4.5%) of B
      (basic) form and a negligible percentage (about 0.5%) of I (intermediate) form.
      In the urine of 22 exposed workers with U-Cd<2 microg/gCr, the percentages of U
      NAG isoenzymes were not different from non-exposed. In the urine of six workers
      with 2 microg/gCr< or =U-Cd<10 microg/gCr the percentage (8.34+/-0.91) of
      isoenzyme B (U-NAG-B), a marker of lesional enzymuria, was statistically
      increased (P<0.05) compared to non-exposed (4.42+/-0.56). These results suggest
      that adopting a biological limit for U-Cd equal to 10 microg/gCr might not be
      sufficiently protective. The increase in U-NAG-B content at 2 microg/gCr<U
      Cd</=10 microg/gCr is probably due to a lesion of the proximal tubule caused by
      the metal which might follow an induction of the apoptotic process.

PMID- 10900293
TI  - Vascular endothelial markers, von Willebrand factor and thrombomodulin index, are
      specifically elevated in type 2 diabetic patients with nephropathy: comparison of
      primary renal disease.
AB  - To elucidate the hypothesis that albuminuria in diabetic subjects reflects
      widespread vascular damage, plasma markers for vascular endothelial damage was
      measured in diabetic subjects with various degrees of albuminuria and compared to
      results in patients with primary renal disease. The groups consisted of 31 non
      diabetic patient controls with normoalbuminuria, 109 type 2 diabetic patients
      with normo- micro- and macro-albuminuria, and 16 proteinuric patients with
      primary renal disease. Endothelial markers, plasma von Willebrand factor (vWF)
      and thrombomodulin (TM), were measured by enzyme-linked immunosolvent assay and
      enzyme immunoassay (EIA) methods, respectively. Plasma vWF levels were similar in
      controls (119+/-7%, mean+/-S.E.M.) and diabetic patients with normoalbuminuria
      (139+/-6), but significantly elevated in diabetic patients with microalbuminuria
      (174+/-11) and macroalbuminuria (204+/-17), while the level was not increased in
      patients with primary renal disease (124+/-11). Because plasma TM level was
      strongly affected by kidney function, TM index (TM (FU/ml)/serum creatinine (mg
      %)) was used as an endothelial marker. The TM index was substantially increased
      in diabetic patients with overt nephropathy compared with controls (5.29+/-2.98
      vs. 2.35+/-0.85), whereas this was not observed in patients with primary renal
      disease (3.25+/-0.29). Both vWF and TM index were significantly higher in
      diabetic patients with retinopathy than in the patients without retinopathy.
      These results suggest that generalized vascular endothelial damage occurs in
      diabetic nephropathy including the microalbuminuric stage, which is not
      attributed to kidney damage per se.

PMID- 10900294
TI  - Biological variability in assessing the clinical value of biochemical markers of
      bone turnover.
AB  - Analytical and biological variability of three bone markers, deoxypyridinoline
      (DPD), CrossLaps (CTx) and galactosylhydroxylysine (GHYL) were compared. From 14
      healthy subjects (six women, eight men; age 29-44 years) recruited from our
      laboratory staff, two sets of samples of early morning urine were obtained - four
      samples taken weekly for 4 weeks (all subjects) and three samples taken monthly
      for 3 months from five subjects. Data were expressed as the ratio to creatinine
      concentration. All the methods met the analytical goals (CV(A)< or
      =1/2CV(I(within-subject))) DPD 0.06, CTx 0.05 and GHYL 0.07 with CV(I(within
      subject)) being 0.22, 0.19 and 0.38, respectively. The reference values were of
      limited usefulness particularly for CTx and GHYL, the index of individuality (II)
      being 0.50 and 0.48 respectively. As the index of heterogeneity (IH) was not
      significant, being 0.23 for CTx, 0.28 for DPD and 0.46 for GHYL, which are all
      <1.71 (1+2S.D.), within-subject variances can be used to calculate the reference
      change value (RCV): 0.58 for DPD, 0.54 for CTx and 1. 08 for GHYL. Moreover, we
      found constant variations in DPD and CTx, week to week and month to month. Our
      findings suggest that DPD and CTx provide more reliable results than GHYL,
      showing a lower within-subject variation, a lower and time-constant RCV allowing
      reliable monitoring without regard for timing.

PMID- 10900295
TI  - Detection of monoclonal proteins by capillary electrophoresis using a zwitterion
      in the running buffer.
AB  - Some cases have been reported in which a small monoclonal protein (M-protein)
      cannot be detected by conventional cellulose acetate membrane electrophoresis
      (CAE) or capillary zone electrophoresis (CZE) using a short fused-silica
      capillary. This is probably because these methods do not have the necessary
      sensitivity or resolution. To overcome this problem, we improved the CZE system
      by using a longer capillary and adding a zwitterion to the running buffer (pH
      10.0). A comparison of CZE and CAE demonstrated that with the exception of
      alpha(1)- and alpha(2)-globulin, the correlation was satisfactory in serum
      samples from 34 patients with M-proteins which had been detected by
      immunoelectrophoresis. In addition, a comparison of CZE electropherograms with
      those from CAE showed that small M-proteins that went undetected by CAE could be
      detected by CZE in four patients whose diseases included epipharyngeal carcinoma,
      solitary plasmacytoma, Crow-Fukase syndrome and macroglobulinemia. The improved
      resolution produced by a longer capillary may be effective for the detection of
      small M-proteins.

PMID- 10900296
TI  - Morning and afternoon serum levels of cortisone and cortisol in asthmatic
      patients.
AB  - While the diurnal change of serum cortisol in asthmatics has been suggested to
      influence the occurrence of attacks, this relation remains controversial. Serum
      concentrations of cortisol, cortisone, and cortisol precursors were measured in
      the morning and in the afternoon in asthmatic patients by reversed-phase high
      performance liquid chromatography. Cortisol and cortisone were detected but their
      precursors were not. In remission or during attacks, the serum cortisone level in
      the morning was significantly lower than that in the afternoon, and the serum
      cortisol level in the morning did not significantly exceed that in the afternoon,
      which differs from the normal diurnal patterns. In patients with severe asthma in
      remission, the diurnal pattern of serum cortisone and cortisol was opposite to
      that seen in normal controls. During the attack, the serum cortisol level showed
      a lesser increase in the afternoon than in the morning. In patients with
      persistent asthmatic attacks, the serum cortisone level in the afternoon showed a
      significant increase as compared with that in remission while their serum
      cortisol level in the afternoon was equal to that in remission. The diurnal
      pattern and the duration of asthmatic attacks might be taken into consideration
      for steroid treatment of asthma.

PMID- 10900297
TI  - Relationship between metabolic glycaemic control and platelet content of
      glutathione and its related enzymes, in insulin-dependent diabetes mellitus.
AB  - The relationship between glycaemic metabolic control and intracellular
      concentration of reduced glutathione (GSH) and related enzymes GSH-peroxidase
      (GSH-Px), GSH-reductase (GSH-Red), GSH-transferase (GSH-Tr), glucose-6-P
      dehydrogenase (G6PDH), and thioltransferase (TT) in patients with insulin
      dependent diabetes mellitus (IDDM) is controversial. Choosing platelets as cell
      model (as commonly done in previous studies), the aim of this study was to relate
      the platelet content of GSH and related enzymes to glycaemic metabolic control,
      expressed as glycated haemoglobin (HbA1c), as well as to presence of retinopathy
      and nephropathy in 114 IDDM patients. As compared to controls, both GSH and GSH
      Red (geometric means (95% CI)) were significantly increased in platelets of
      diabetic patients: 3.3 (0.7-9.6) vs. 2.4 (0.8-7.6) mmol 10(-9) platelets; P=0.01
      for GSH, and 30.6 (14.7-61.6) vs. 22.2 (8.7-52.2) mU 10(-9) platelets, P=0.0002
      for GSH-Red, and TT activity was marginally decreased in the IDDM group (P=0.06).
      While no clear relationship was present between GSH-related enzymes and HbA1c, a
      trend was present toward a non-linear relation between HbA1c and GSH, being
      significantly related by a parabolic curve (P=0.002). As compared to patients
      with normoalbuminuria (n=88), diabetic patients with increased urinary albumin
      excretion rate (n=26) had a significant decrease in platelet TT concentration
      (3.2 (0.9-6.7) vs. 5.1 (1.9-18.7) mU 10(-9) platelets; P=0.0002), whereas
      retinopathy was not associated to modifications in GSH or in the enzymatic
      pattern. In summary: (a) platelet GSH and GSH-Red are increased in IDDM, while
      other enzymes are unmodified; (b) GSH seems to be related to metabolic control
      according to non-linear parabolic curve; (c) presence of increased albuminuria is
      associated to a selective decrease in platelet TT content.

PMID- 10900298
TI  - Pseudoleukocytosis without pseudothrombocytopenia induced by the interaction of
      EDTA and IgG(2)-kappa M-protein.
AB  - We encountered a patient who showed ethylenediaminetetraacetic acid (EDTA)
      induced pseudoleukocytosis without pseudothrombocytopenia. The patient had IgG
      kappa type monoclonal (M) gammopathy. The total protein concentration was 77 g/l,
      and the gamma-globulin fraction containing M-protein was 23.2%. The white blood
      cell count of the patient's blood anti-coagulated with EDTA was 52300/microl as
      determined using an automated counter, but was within normal limits when counted
      manually by light microscopy using a hemacytometer. Large amounts of a
      transparent substance were observed on blood smears, and white precipitates were
      formed by an interaction of the patient's serum with EDTA. Immunofixation
      electrophoresis showed these precipitates to be of the IgG(2)-kappa type M
      protein. Western blotting analysis showed that the IgG molecules had a molecular
      mass of 155 kDa and were composed of two gamma-chains of approximately 53 kDa and
      two kappa-chains of 27 kDa. Pseudoleukocytosis was also observed when the
      patient's blood was anti-coagulated with O, O'-bis(2-amino-ethyl)-ethyleneglycol
      N,N,N',N'-tetraacetic acid (EGTA) or sodium citrate, but not with lithium
      heparin. The present case seems to be the first report of pseudoleukocytosis
      induced by the interaction of EDTA and IgG(2)-kappa type M-protein.

PMID- 10900299
TI  - Absence of relationship between plasma Lp(a), Lp-AI, anti-oxidized LDL
      autoantibodies, LDL immune complexes concentrations and restenosis after
      percutaneous transluminal coronary angioplasty.
AB  - To determine the relation between the concentration of Lp(a), LpAI, immunological
      markers of LDL oxidation (antioxidized-LDL autoantibodies (LDL-AB), LDL immune
      complexes (LDL-IC)) and restenosis after percutaneous transluminal coronary
      angioplasty (PTCA) in a Caucasian population (France), we studied 77 consecutive
      patients who successfully underwent PTCA. All were evaluated by follow-up
      angiography at an average of 6 months after PTCA and were divided into two
      groups: existence of restenosis (32 patients, group (G+)) and absence of
      restenosis (45 patients, negative group (G-)). The prevalence of diabetes
      mellitus was higher in the restenosis positive group than in the negative group
      (28% versus 2% respectively, P=0.001). Before and after adjustment in diabetes
      mellitus frequency there was no difference in the usual lipid parameters (total
      cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, phospholipids,
      apolipoprotein AI, apolipoprotein B) between the two groups of patients nor in
      the other parameters (Before adjustment: Lp(a): 0.306+/-0.352 g/l (G+) vs.
      0.263+/-0.270 g/l (G-); LpAI: 0.414+/-0.126 g/l (G+) vs. 0.390+/-0.092 g/l (G-);
      LDL-AB: arbitrary unit (AU) 3.75+/-1.91 (G+) vs. 3.67+/-1.24 (G-); LDL-IC: (AU)
      0.93+/-0.82 (G+) vs. 0.86+/-0.44 (G-)). Spearman correlation coefficients did not
      report any correlation between late loss, loss index, gain and the above
      mentioned plasma parameters. In conclusion, usual tested plasma lipids, Lp(a),
      LpAI and in vivo markers of LDL oxidation (LDL-AB and LDL-IC) are not risk
      factors for restenosis after PTCA in this French population.

PMID- 10900300
TI  - Normalization rate and cellular localization of phosphatidylethanol in whole
      blood from chronic alcoholics.
AB  - Phosphatidylethanol (PEth) is an abnormal phospholipid which is formed in the
      presence of ethanol, via the action of phospholipase D (PLD). PEth in blood is a
      potential marker of alcohol abuse. The present study was made to determine the
      compartmentalization and the elimination rate of PEth in human whole blood. PEth
      was assayed by an improved HPLC technique, with evaporative light-scattering
      detection. Blood from six alcoholic males was separated into different blood cell
      fractions. The PEth concentration in whole blood was 2.5+/-0.9 and 1.9+/-1.1
      micromol/l in erythrocytes. Only one subject had detectable PEth in the
      mononuclear cells. Fifteen patients (13 men, two women) with chronic alcoholism,
      were followed as inpatients, after admission to an alcohol detoxification clinic.
      PEth, carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase
      (GGT) were measured on days 1, 3, 5 and 7 after admission. Linear regression
      analysis of logarithmic PEth values in individuals, with measurable PEth at day
      1, gave a good fit (P<0.001) with the one-compartment elimination model. The half
      life was calculated as 4.0+/-0.7 days. A weak significance (P<0.05) was observed
      in the correlation of PEth at day 1 and half-life values of the same subjects.

PMID- 10900301
TI  - Monoclonal antibodies to human apolipoproteins: application to the study of high
      density lipoprotein subpopulations.
AB  - We produced, selected and cloned hybridomas that secrete monoclonal antibodies
      against human apolipoprotein (apo) A-I. All of the antibodies corresponded to the
      IgG(1) subclass and were named 1C11, 2B4, 2C10, 7C5, 8A4 and 8A5. The antibodies
      were characterized by their reactivity with whole lipoproteins, apolipoproteins,
      synthetic peptides and fragments generated by cleavage of the apo A-I. Three of
      the monoclonal antibodies studied (2B4, 2C10 and 7C5) were similarly inhibited by
      an amino-terminal peptide (amino acid sequence 1-20) of apo A-I, whereas
      antibodies 1C11, 8A4 and 8A5 had no reaction. Other results show that monoclonal
      antibody 1C11 recognizes an epitope located between amino acids 135-148. We
      evaluated the monoclonal antibody 8A4 against different HDL subpopulations by
      competitive displacement analysis and it showed a similar reactivity with the HDL
      particles: LpA-I and LpA-I:A-II. This antibody was used to standardize a sandwich
      ELISA to quantitate LpA-I in plasma. We conclude that these monoclonal antibodies
      are relevant for the study of apo A-I epitope expression and for quantitating apo
      A-I containing lipoparticles.

PMID- 10900302
TI  - High galactosylation of oligosaccharides in umbilical cord blood IgG, and its
      relationship to placental function.
AB  - N-linked oligosaccharides on human serum IgGs have been reported to modulate IgG
      function. We studied umbilical cord blood to determine whether neonatal IgGs have
      characteristic structures related to developmental and pathological status.
      Oligosaccharide patterns of serum IgG from 45 umbilical cord blood samples were
      characterized by HPLC, and compared with those of serum IgG from 11 normal
      adults. Oligosaccharyl amines from purified IgG were released by recombinant N
      glycanase, labeled with fluorescence reagent FMOC (9-fluorenylmethyl
      chloroformate), and analyzed quantitatively by high-pressure liquid
      chromatography (HPLC). Increased galactosylation was observed in cord blood. The
      ratio of galactosylated to non-galactosylated oligosaccharides on IgG was 7.90+/
      3.92 (mean+/-S.D.) in cord blood, significantly higher than the ratio in adults
      (1.60+/-0.62, P<0.0001). There were weak but not significant correlations between
      the ratio and birth weight, gestation period, mother's age, and no correlation
      with serum IgG concentration. The ratio was lower for premature or intra-uterine
      growth retarded neonates. Our results, in conjunction with previous reports that
      galactosylated IgG stimulates Fc-mediated phagocytosis of monocytes, suggest that
      increased galactosylation of IgG enhances neonatal immunity.

PMID- 10900303
TI  - Enzyme-linked immunosorbent assay for anti-tropomyosin antibodies and its
      clinical application to various heart diseases.
AB  - Tropomyosin is one of the key proteins for muscle contraction. We developed an
      enzyme-linked immunosorbent assay for antibodies to porcine muscle tropomyosin
      and measured serum anti-tropomyosin antibodies in patients with heart diseases
      and in normal controls. The mean values of absorbance in the ELISA assay of
      patients with ischemic heart disease (n=36, P<0.001), dilated cardiomyopathy
      (n=28, P<0.005), valvular heart disease (n=27, P<0.05), and collagen disease
      (n=38, P<0.05) were significantly higher than those of normal controls (n=53),
      but the value in patients with hypertrophic cardiomyopathy (n=19) was not
      significantly different from that of normal controls. When the cut-off value was
      fixed at the mean+2 SD of absorbance in normal controls, positive reactions were
      found in 19.4%, 7.1%, 18.5% and 15.8% of patients with ischemic heart disease,
      dilated cardiomyopathy, valvular heart disease, and collagen disease,
      respectively. An inhibition study revealed that anti-tropomyosin antibodies were
      different from anti-myosin antibodies, but there was a partial cross-reactivity
      between the two. Thus, there was a weak correlation of the titers of the two
      types of antibody within the group of heart diseases. These data indicate that
      measurement of anti-tropomyosin antibodies by ELISA is helpful for detecting
      autoimmune abnormalities in various heart diseases.

PMID- 10900304
TI  - Is endogenous isoprene the only coeluting compound in the measurement of breath
      pentane?
AB  - Pentane is a widely used index of lipid peroxidation. Although isopentane, an
      isomer of pentane, is a major component of ambient air in urban areas, many
      studies have disregarded the possibility that this compound is coeluted in the
      measurement of breath pentane. In the present study, a gas chromatograph equipped
      with a cold trap apparatus and a large-bore glass capillary column was used for
      determination of pentane, isopentane and isoprene in breath and ambient air.
      Isoprene was detected in all subjects at a concentration higher than that in the
      ambient air. However, the concentrations of breath pentane and isopentane were
      similar to, or less than, those of the ambient air. We suggest that great care is
      required in the measurement of breath pentane so that endogenous isoprene and
      ambient isopentane are not coeluted.

PMID- 10900305
TI  - Use of longer extension phases to improve yield of high molecular weight products
      in differential display PCR.

PMID- 10900306
TI  - Factitious hearing loss and otorrhea in an adolescent boy.
AB  - Asialo, or beta(2), transferrin occurs in cerebrospinal fluid and a few other
      body fluids, e.g., perilymph and aqueous humor. It is used clinically as a marker
      protein to detect CSF otorrhea and rhinorrhea. Asialo-transferrin is separated
      from sialylated serum transferrin glycoforms by electrophoresis and detected by
      Western blotting. Potential pitfalls in interpreting Western blots occur when
      other transferrin isoforms approximate the migratory behavior of asialo
      transferrin. In the present report an adolescent boy was seen by an
      otolaryngologist for otorrhea and acute hearing loss. The otorrhea fluid,
      subsequently identified as saliva, contained a transferrin isoform with
      electrophoretic mobility similar to that of asialo-transferrin.

PMID- 10900332
TI  - TrkA is necessary for the normal development of the murine thymus.
AB  - Nerve growth factor (NGF) and its signal-transducing receptor TrkA are expressed
      in the thymus. However, their possible role during thymic organogenesis is
      unknown. Here we analyze the thymus of trkA-kinase deficient 2-week-old mice.
      trkA-kinase +/+ and +/- mice had a normal thymus, whereas the thymus of trkA
      kinase -/- mice showed lack of delimitation between the cortex and medulla, lower
      thymocyte density, and the presence of epithelial cell islands and numerous cysts
      lined with endodermal epithelium. The present results indicate that TrkA is
      necessary for the normal development of the thymus, and that its absence causes
      an arrest in the differentiation of endodermal epithelial cells. Whether this
      lack of differentiation has functional implication has yet to be determined.

PMID- 10900331
TI  - Regulation of cell cycle proteins by TNF-alpha and TGF-beta in cells of
      oligodendroglial lineage.
AB  - Proliferation and apoptosis are two dynamic, interrelated processes that are
      regulated by growth factors and cytokines. We investigated the effects of tumor
      necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta)
      on apoptosis and regulation of cell cycle proteins in OLG lineage cells. We found
      that: (1) both cytokines enhanced apoptosis in neonatal pre-OLGs but only
      TNFalpha-mediated apoptosis persisted in the presence of a mitogen, fibroblast
      growth factor (FGF); (2) cell cycle proteins such as p21(waf1/cip1), p27(kip1),
      cyclin D1 and PCNA were differentially regulated by TNF-alpha and TGF-beta. We
      conclude that differential modulation of cell cycle proteins by TNF-alpha and TGF
      beta contributes to the diversity of their biological effects in OLG lineage
      cells.

PMID- 10900333
TI  - High-dose mouse immunoglobulin G administration suppresses Theiler's murine
      encephalomyelitis virus-induced demyelinating disease.
AB  - We studied the effect of high-dose mouse IgG on TMEV-induced demyelinating
      disease (TMEV-IDD). We injected TMEV intracerebrally into susceptible SJL/J mice
      and induced TMEV-IDD. Mouse IgG were injected intraperitonealy, and clinical
      course and various immunological indicators were studied. The results show that
      TMEV-IDD was significantly suppressed both clinically and histologically (P<0.01)
      when IgG were administered in the effector phase. The delayed type
      hypersensitivity and T cell proliferative response specific for TMEV were
      decreased by this treatment. In an ELISPOT assay, the number of TNF-alpha
      producing lymphocytes in the spinal cords was low in high-dose IgG treated mice
      compared with PBS treated control mice. These data suggest that administration of
      IgG suppresses TMEV-IDD and may be promising treatment to prevent exacerbation of
      human multiple sclerosis.

PMID- 10900334
TI  - T cell recognition of muscle acetylcholine receptor in ocular myasthenia gravis.
AB  - We examined the proliferative response of blood CD4(+) cells to muscle
      acetylcholine receptor (AChR) subunits and the epitope repertoire of the epsilon
      and gamma subunits, in ocular myasthenia gravis (oMG) patients and healthy
      subjects. oMG patients seldom recognized all subunits. The frequency and
      intensity of recognition was the same for all subunits, irrespective of the
      disease duration. The responses in oMG were lower than in generalized myasthenia
      gravis. Healthy subjects had frequent, low responses to one or more subunits. oMG
      patients recognized several epitopes on the gamma and epsilon subunits, that
      partially overlapped those recognized in gMG. The subunits and epitopes
      recognized by individual oMG patients changed over time. Thus, oMG patients have
      minimal and unstable sensitization of anti-AChR CD4(+) cells, in agreement with
      their low and inconsistent synthesis of anti-AChR antibody.

PMID- 10900335
TI  - Elevated interferon-gamma in CNS inflammatory disease: a potential complication
      for bone marrow reconstitution in MS.
AB  - Bone marrow transplantation (BMT) is increasingly used to treat Multiple
      Sclerosis (MS) a CNS inflammatory disease with elevated CNS and systemic IFNgamma
      levels. We wished to determine the effect of IFNgamma on BM graft survival in a
      transgenic mouse model for chronic MS. BM transplantation into transgenic mice
      which express elevated levels of IFNgamma in the CNS was unsuccessful. By
      contrast, there was 100% survival of even fully allogeneic, T-depleted
      transplants to transgenics that over express TNFalpha in the CNS, using the same
      MBP promoter. IFNgamma was detectable in spleen of irradiated mice but levels
      were higher in IFNgamma transgenics. BM transplantation into IFNgamma-deficient
      recipients also had a high failure rate. Transplants of BM from mice lacking
      expression of IFNgamma-receptor failed, whereas IFNgamma-deficient grafts
      survived, suggesting that IFNgamma response status of the graft can also
      positively influence survival. IFNgamma therefore has a dual role in BM
      transplantation and the outcome will depend on relative levels of cytokine
      expression.

PMID- 10900336
TI  - Genetic and epigenetic influence on EAE phenotypes induced with different
      encephalitogenic peptides.
AB  - Different encephalitogenic peptides can induce two distinct experimental
      autoimmune encephalomyelitis (EAE) phenotypes in different mouse strains. To
      determine whether different peptides induce distinct phenotypes in genetically
      identical mice, parental strain and (SJLXC3H/HeJ)F1 mice were sensitized with
      myelin proteolipid protein peptide p139-151 or p215-232. p139-151 was non
      encephalitogenic in C3H/HeJ mice and p215-232 was non-encephalitogenic in SJL
      mice. p139-151 induced typical acute EAE in SJL and F1 mice with most CNS
      inflammatory/demyelinating lesions located in the spinal cord. p215-232 induced
      mild clinical disease in only two of 10 C3H/HeJ mice; in 11 of 13 F1 mice (85%)
      it induced a disease spectrum that included typical paralytic acute EAE with a
      predominance of spinal cord lesions and later-onset mild EAE with predominance of
      brain stem/cerebellar lesions. Thus, the EAE phenotype induced in F1 mice by one
      encephalitogen, e.g. p139-151, can be the same as that induced in the susceptible
      parent. However, other encephalitogenic peptides, e.g. p215-232, may induce a
      broad range of heterogeneous EAE phenotypes in syngeneic mice. These data
      indicate that in some encephalitogenic responses, epigenetic factors influence
      EAE incidence, time of onset, severity, neurological signs and CNS lesion
      distribution.

PMID- 10900337
TI  - The suppressive effect of TGF-beta on IL-12-mediated immune modulation specific
      to a peptide Ac1-11 of myelin basic protein (MBP): a mechanism involved in
      inhibition of both IL-12 receptor beta1 and beta2.
AB  - Transforming growth factor (TGF)-beta exerts a counter-regulatory effect on
      interleukin (IL)-12-mediated immune modulation. The underlying mechanism is not
      fully understood. Here we demonstrate that the expression of IL-12Rbeta1 and IL
      12Rbeta2 in MBP peptide Ac1-11-primed splenocytes is upregulated upon antigen
      stimulation. TGF-beta induces an unresponsiveness of these primed splenocytes to
      IL-12 signaling through a mechanism involved in inhibition of both IL-12Rbeta1
      and beta2. The modulation of IL-12Rbeta1 and beta2 expression by Ac1-11
      stimulation and TGF-beta is mainly involved in CD4+ population. These data
      indicate that both IL-12Rbeta1 and IL-12Rbeta2 expression are crucial during T
      cell activation. TGF-beta-induced inhibition of IL-12R expression will reduce
      cellular immune responses during IL-12-mediated autoimmune disease.

PMID- 10900338
TI  - Distinct domains of IFNalpha mediate immune and analgesic effects respectively.
AB  - Interferon-alpha (IFNalpha) is not only an immunoregulatory factor, but is also
      an analgesic molecule. The analgesic effect of IFNalpha was mediated by mu opioid
      receptor. After the 129th Tyr residue of human IFNalpha was mutated to Ser, the
      antiviral activity almost disappeared, but there still remained a strong
      analgesic activity that could be blocked by naloxone. These results indicate that
      there exist distinct domains in the IFNalpha molecule, which mediate immune and
      analgesic effects respectively, and suggest that there are different receptor
      mechanisms inducing immune and analgesic effects of IFNalpha. However, although
      the antiviral activity of IFNalpha decreased to 34.1% of wild type IFNalpha after
      the 122nd Tyr residue was changed to Ser, the analgesic activity of this mutant
      was lost completely. There were significant cross reactivities between INFalpha
      and anti-opioid sera. These studies show strong structural and functional
      similarities between INFalpha and opioid peptides, and inferred that the
      analgesic domain locates around the 122nd Tyr residue of IFNalpha molecule in
      tertiary structure.

PMID- 10900339
TI  - Effect of stress on the production of O(2)(-) in alveolar macrophages.
AB  - Alveolar macrophages (AM) of male rats (200-250 g), stressed or not, were
      evaluated with relationship to superoxide production (SP). Plasma levels of
      corticosterone were measured. The control group showed larger SP than the
      stressed group in all intervals of time. Exposure in vitro of AM to a synthetic
      glucocorticoid for 40 min (the same time of restraint stress) inhibits SP.
      Therefore, it seems under stress situations there is an increase of plasma levels
      of corticosterone and a decrease of SP in AM after stimulation with PMA. O(2)(-)
      is a potent microbicide and its reduction could cause the loss of microbicidal
      activity of AM.

PMID- 10900341
TI  - Noradrenaline induces phosphorylation of ERK-2 in human peripheral blood
      mononuclear cells after induction of alpha(1)-adrenergic receptors.
AB  - alpha(1)-Adrenergic receptors (ARs) are not expressed by peripheral blood
      mononuclear cells (PBMCs) of healthy human individuals. However, in the present
      study we show that alpha(1)-ARs can be induced in lymphocytes after culturing
      with either the mitogen PHA or the glucocorticoid dexamethasone. Moreover,
      incubation of these activated PBMCs with noradrenaline (NA) results in enhanced
      phosphorylation of ERK-2, a kinase involved in the activation of many immune
      functions. Similar induction of alpha(1)-AR mRNA with concomitant NA-induced
      activation of ERK-2 occurs in monocytes after culture with LPS. Our results
      demonstrate that functional alpha(1)-ARs can be induced on PBMCs and that these
      alpha(1)-ARs mediate NA-induced activation of ERK-2.

PMID- 10900340
TI  - Activation of glial cells by human coronavirus OC43 infection.
AB  - Multiple sclerosis (MS) is an immune-mediated demyelinating disease that could be
      triggered by a viral infection. Coronaviruses induce an MS-like disease in
      rodents, are neuroinvasive in humans and can infect primary cultures of human
      astrocytes and microglia. Infection of the human astrocytic cell line U-373MG by
      the OC43 strain of human coronavirus caused an upregulation of IL-6, TNF-alpha,
      and MCP-1 mRNA expression. This virus also modulated the activity of matrix
      metalloproteinases-2 and -9 and augmented nitric oxide production in both U-373MG
      cells and the human microglial cell line CHME-5. Thus, a coronaviral infection of
      glial cells could lead to the production of inflammatory molecules that have been
      associated with central nervous system pathologies such as MS.

PMID- 10900342
TI  - A plasmid construct encoding murine interferon beta antagonizes the replication
      of herpes simplex virus type I in vitro and in vivo.
AB  - In the present study, we employed a plasmid DNA encoding murine interferon (IFN)
      beta to assess its antiviral efficacy in an in vitro transfection-infection assay
      and in an ocular HSV-1 infection model of mice. In the in vitro assay,
      transfection of mouse fibroblasts with the IFN-beta transgene resulted in a 17
      fold or greater reduction in the viral load of HSV-1 at a multiplicity of
      infection (MOI) of 1 compared to that of those mice treated with the plasmid
      control. RT-PCR analysis of representative immediate early (ICP27), early
      (thymidine kinase, TK) and late (VP16) viral genes found no changes in the level
      of expression comparing the IFN-beta transgene- to the vector-treated control
      group, suggesting that the IFN-beta transgene may act at the post-transcriptional
      level of viral replication. In the ocular HSV-1 infection model, topical
      application of the plasmid DNA encoding murine IFN-beta onto mouse cornea
      enhanced cumulative survival and significantly reduced the viral load of HSV-1 in
      the eyes and trigeminal ganglia of mice at both day 3 and 6 post-infection
      compared with mice treated with the plasmid vector control or normal saline.
      Neutralizing antibody to IFN-beta blocked the protective effect elicited by the
      IFN-beta transgene. Unlike the in vitro experiment, viral gene expression was
      reduced in the trigeminal ganglion of mice pre-treated 24 h with the IFN-beta
      transgene day 3 (ICP27 and VP16) and day 6 (ICP27, TK, DNA polymerase, and VP16)
      post-infection in comparison to mice treated with the plasmid vector control as
      determined by semi-quantitative RT-PCR.

PMID- 10900343
TI  - Inhibition of experimental allergic encephalomyelitis in the Lewis rat by
      paclitaxel.
AB  - Experimental allergic encephalomyelitis (EAE), an animal model for multiple
      sclerosis (MS), is useful for preclinical testing for agents to be considered for
      treatment for this human demyelinating disease. Microtubules in lymphocytes play
      an important role in the cascade of human T cell activation, and paclitaxel
      (PTX), a microtubule stabilizer, can inhibit T cell function. A new formulation
      of micellar PTX, free of Cremophor and ethanol, was tested for its effect on the
      induction of EAE in Lewis rats. Adoptive EAE was induced with an encephalitogenic
      T cell line activated with guinea pig myelin basic protein (GP MBP) peptide 68
      88. PTX (10 mg/kg) was administered 24 and 72 h after cell transfer. The clinical
      signs, fulminating in controls, were completely blocked by PTX, but mild CNS
      inflammation remained unaltered. A similar dose of PTX, given on days 6 and 8 to
      animals developing active EAE after immunization with GP MBP peptide 68-88 in
      complete Freund's adjuvant, greatly reduced the severity of paralysis and delayed
      the onset of disease by 8-9 days. Marked weight loss and severe toxicity were
      noted with higher and more prolonged administration. In vitro micellar PTX
      inhibited activation of encephalitogenic T cells by both specific antigen and
      mitogen. Lower doses and longer treatment programs may provide effective
      treatment with acceptable adverse effects with this agent in the treatment of
      inflammatory demyelinating disease.

PMID- 10900344
TI  - Accelerated development of neurochemical and behavioral deficits in LP-BM5
      infected mice with targeted deletions of the IFN-gamma gene.
AB  - Mice homozygous for a germline deletion of the interferon-gamma gene (IFN-gamma (
      /-)) were infected with the LP-BM5 (BM5) retrovirus mixture to determine if the
      inability to produce IFN-gamma reduces collateral CNS damage associated with
      chronic neuroinflammation. Virus burdens in spleens and brains of infected mice
      were comparable, but spatial memory deficits were manifested earlier and to a
      greater extent in BM5/IFN-gamma (-/-) mice. The mice with spatial memory deficits
      showed considerable degradation of axons and microtubules, along with apoptosis
      of striatal neurons. These lesions were accompanied by extensive infiltration of
      perivascular spaces and ventricles by iNOS-positive leukocytes, and a 17-fold
      increase in CSF glutamate levels. Despite high levels of VCAM and ICAM expression
      on cerebral vasculature endothelia, the serum levels of soluble ICAM-1 were
      significantly decreased in BM5/IFN-gamma (-/-) mice, which may contribute to the
      enhanced leukocyte infiltration and subsequent neuronal damage. These results
      suggest that the presence of IFN-gamma is necessary at some points in the
      inflammatory process to protect against neurodegeneration.

PMID- 10900345
TI  - Epitope recognition and T cell receptors in recurrent autoimmune anterior uveitis
      in Lewis rats immunized with myelin basic protein.
AB  - Lewis rats immunized with myelin basic protein (MBP) develop experimental
      autoimmune encephalomyelitis (EAE) and associated anterior uveitis (AU). Rats
      recover and become resistant to further reinduction of EAE. We investigated
      whether the resistance to reinduction of EAE was associated with the resistance
      to AU in LEW rats reinjected with MBP. We demonstrated that while rats remained
      resistant to EAE, they become susceptible to uveitis after recovery, and suffered
      a second episode of disease. The susceptibility to reinduced disease was
      associated with the recognition of new MBP epitopes. In contrast to the initial
      episode of AU, TCR Vbeta8.2 predominance was not observed in the iris/ciliary
      body. Our results suggest that T cells specific for MBP, which are rapidly
      reactivated when re-exposed to antigen, are sufficient to induce clinical uveitis
      in LEW rats. This process may involve a shifting of T cell specificity from the
      major encephalitogenic peptide utilizing the Vbeta8.2 receptor to a more diverse
      cell repertoire.

PMID- 10900346
TI  - The pineal gland and cancer. I. Pinealectomy corrects congenital hormonal
      dysfunctions and prolongs life of cancer-prone C3H/He mice.
AB  - Hormonal derangements almost invariably anticipate and signal the onset of
      tumors. Chronic, nocturnal melatonin administration delays aging in normal
      strains of mice. On the contrary it promotes and accelerates the onset of tumors
      in the cancer-prone strain of C3H/He mice. Grafting of a young pineal gland into
      aging mice prolongs their longevity and maintains juvenile circadian hormonal
      functions while pinealectomy (Px) does the opposite. We investigated if Px in
      C3H/He mice would modify their congenitally deranged pituitary function and
      affect their longevity. It was found that contrarily to Px in normal mice, Px in
      C3H/He mice remarkably maintains juvenile night levels of thyroid hormones and
      lipids, preserves a cell-mediated immune response and significantly prolongs
      their life. The pineal gland and its pathology may be the key for understanding,
      not only the causes of metabolic aging, but also the origin of those congenital
      or progressive aging-related hormonal alterations preceding onset of all tumors
      and thus allow preventive corrective interventions with pineal-derived agents.

PMID- 10900347
TI  - The type IV phosphodiesterase specific inhibitor mesopram inhibits experimental
      autoimmune encephalomyelitis in rodents.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease with
      pathological features reminiscent of those seen in multiple sclerosis and thus
      serves as an animal model for this disease. Inhibition of type IV
      phosphodiesterase (PDE IV) in animals with this disease has been shown to result
      in amelioration of disease symptoms. Here we describe the immunomodulatory
      activity of the novel potent and selective PDE IV inhibitor mesopram. In vitro,
      mesopram selectively inhibits the activity of type 1 helper T (Th1) cells without
      affecting cytokine production or proliferation of type 2 helper T (Th2) cells.
      Administration of mesopram to rodents inhibits EAE in various models. Clinically,
      EAE is completely suppressed by mesopram in Lewis rats. This is accompanied by a
      reduction of inflammatory lesions in spinal cord and brain. RT-PCR analysis
      revealed a marked reduction in the expression of interferon-gamma (IFN-gamma) and
      tumor necrosis factor-alpha (TNF-alpha) in the brains of these animals.
      Furthermore, the ex vivo production of Th1 cytokines by activated spleen cells
      derived from mesopram-treated animals is significantly reduced compared to
      vehicle-treated controls. Amelioration of the clinical symptoms is also observed
      during chronic EAE in mesopram-treated SJL mice as well as in relapsing-remitting
      EAE in SWXJ mice using a therapeutic treatment regimen. These data demonstrate
      the anti-inflammatory activity of mesopram and provide a rationale for its
      clinical development.

PMID- 10900348
TI  - The role of TNF-alpha during Wallerian degeneration.
AB  - The role of TNF-alpha in the course of Wallerian degeneration of the sciatic
      nerve was studied in control and TNF-alpha deficient mice. In control animals,
      the characteristic phenomena of Wallerian degeneration such as axon and myelin
      degeneration as well as macrophage recruitment with subsequent myelin removal
      were observed. In TNF-alpha deficient mice, in contrast, macrophage recruitment
      into the degenerating nerves was impaired resulting in a delayed myelin removal.
      However, the myelin phagocytic capacity of macrophages was not affected as it
      could be demonstrated by a similar myelin load of control and TNF-alpha deficient
      macrophages. These data indicate that the main function of TNF-alpha during
      Wallerian degeneration is the induction of macrophage recruitment from the
      periphery without affecting myelin damage or phagocytosis.

PMID- 10900349
TI  - PECAM1, MPO and PRKAR1A at chromosome 17q21-q24 and susceptibility for multiple
      sclerosis in Sweden and Sardinia.
AB  - Using genome screen, DNA sequence and mapping data, we scanned the human
      chromosomal region 17q21-q24 for polymorphic markers in single copy genes. Three
      such genes were identified: the gene for myeloperoxidase (MPO) at 17q21.3-q23.2,
      containing a CA-microsatellite in the eighth intron and a functional single base
      substitution (G to A) in the promoter region, the platelet endothelial cell
      adhesion molecule-1 gene (PECAM1) at 17q23, which has a CA-repeat sequence in the
      sixth intron, and the gene for the regulatory subunit RIalpha of cAMP-dependent
      protein kinase (PRKAR1A) at 17q23-q24, in which a GA-microsatellite was detected
      in the 5'-flanking region. Association of these polymorphisms with multiple
      sclerosis (MS) was studied in a Swedish case-control population of 199 MS
      patients and 145 control subjects, and in 203 simplex families from Sardinia.
      None of these polymorphic genes was found to be a genetic marker for disease
      susceptibility. These results are in contrast with previous studies on the
      involvement of MPO in MS and suggest that the elevated expression of PECAM-1 in
      MS, as earlier documented, is related to transactivation by other gene products.

PMID- 10900350
TI  - Co-expression of beta-endorphin with adhesion molecules in a model of
      inflammatory pain.
AB  - Opioid-containing immunocytes migrate to inflamed sites where they release beta
      endorphin which activates peripheral opioid receptors and produces analgesia. The
      immigration of immunocytes to sites of inflammation is mediated by adhesion
      molecules. In this study, the expression of L-, P-, E-selectin and platelet
      endothelial adhesion molecule-1 (PECAM-1) in relation to beta-endorphin
      expression was analyzed by immunohistochemistry in inflamed tissues. The
      proportion of immunocytes expressing L-selectin was increased in inflamed lymph
      nodes and subcutaneous paw tissue. P-selectin and PECAM-1 were constitutively
      expressed on endothelia of noninflamed lymph nodes and subcutaneous tissue and
      were upregulated in inflammation. beta-endorphin positive cells expressed L
      selectin in lymph nodes and subcutaneous tissue. Upregulation of P-selectin and
      PECAM-1 and the co-localization of L-selectin and beta-endorphin in immunocytes
      suggest an important role of these adhesion molecules for the recruitment of
      immunocytes containing beta-endorphin to sites of painful inflammation.

PMID- 10900351
TI  - Characterization of acute versus chronic relapsing autoimmune encephalomyelitis
      in DA rats.
AB  - This study was undertaken to better understand the role of cytokines in the
      pathogenesis, especially in the mechanisms of relapse, of experimental autoimmune
      encephalomyelitis (EAE). For this purpose, we induced acute and chronic relapsing
      (CR) EAE in DA rats and determined several immunological parameters in rats at
      various stages of two types of EAE. Histopathological analysis revealed that
      there was no significant difference in the severity of inflammation in the spinal
      cord lesions between the two groups. However, demyelination was observed only in
      rats with CR EAE. Cytokine analysis by competitive PCR demonstrated that levels
      of TNF-alpha, IL-6 and IL-12 p40 mRNA in the spinal cord at the first attack of
      CR EAE were significantly higher than those at the peak stage of acute EAE. The
      mRNA expression of anti-inflammatory cytokines, IL-10 and TGF-beta1, was
      generally low in both acute EAE and the first attack of CR EAE and upregulated at
      later stages of CR EAE. These findings suggest that persistent high-level
      expression of pro-inflammatory cytokines is closely associated with demyelination
      and relapse of EAE. In contrast, anti-inflammatory cytokines play only a minor
      role in the relapse.

PMID- 10900352
TI  - Flow cytometric analysis of infiltrating cells in the peripheral nerves in
      experimental allergic neuritis.
AB  - Experimental autoimmune neuritis (EAN) is an animal model that shares clinical,
      pathological and electrophysiological features with the human disease Guillain
      Barre syndrome (GBS). In this study, we isolated and characterized by fluorescent
      activated cell sorter (FACS) phenotype of the inflammatory cells infiltrating
      cauda equina (CE) of Lewis rats at the active stage of the disease. We found that
      at this stage of EAN macrophages (Mphi) and alphabeta T cells were two major
      populations isolated from CE. We also found that among total cell population
      isolated from CE, gammadelta T and NK cells composed two small but distinct
      populations, while B cells were negligible. We characterized phenotype of
      alphabeta T cells in CE as CD45RC(+)CD8(+) (activated cytotoxic lymphocytes) and
      CD45RC(-)CD4(+) (memory Th cells). The phenotype of gammadelta T cells was found
      to be consisted of only CD45RC(+)CD8(+) cells. Both alphabeta and gammadelta T
      cells in CE expressed a higher level of CD25, CD44 and CD54 activation markers
      compared to the other tissues. Immunohistochemistry demonstrated that gammadelta
      T cells existed apart from the intense cellular infiltrate. This is the first
      report on the isolation and FACS analysis of CE-infiltrating cells, contributing
      a new and alternative approach to study the inflammatory lesions in EAN. We
      conclude that both alphabeta and gammadelta T cells have a unique
      activation/inflammatory phenotype required to traffic through and be retained in
      the peripheral nerves during EAN.

PMID- 10900353
TI  - Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple
      sclerosis central nervous system tissue.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system (CNS) characterised by perivascular inflammatory cell infiltrates
      and plaques of demyelination. Chemokines have been shown to play an important
      role in the activation and directional migration of cells to sites of CNS
      inflammation. The action of chemokines requires the expression of their
      complementary chemokine receptors by their target cells. We have examined the
      expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in post-mortem MS
      CNS tissue using single- and double-labelling immunocytochemistry techniques. Low
      levels of CCR2, CCR3 and CCR5 were expressed by microglial cells throughout
      control CNS tissue. In chronic active MS lesions CCR2, CCR3 and CCR5 were
      associated with foamy macrophages and activated microglia. CCR2 and CCR5 were
      also present on large numbers of infiltrating lymphocytes. A smaller number of
      CCR3-positive lymphocytes were present, but we also noted CCR3 and CCR5 on
      astrocytes in five of the 14 cases of MS investigated, particularly associated
      with processes around vessels and at the glia limitans. Ligands for CCR2 and CCR3
      include MCP-1 and MCP-3 which were co-localised around vessels with the
      infiltrating leukocytes, but were also present in unaffected areas of cortex. The
      elevated expression of CCR2, CCR3 and CCR5 in the CNS in MS suggests these beta
      chemokine receptors and their ligands play a role in the pathogenesis of MS.

PMID- 10900354
TI  - Characterization of T cell lines derived from glatiramer-acetate-treated multiple
      sclerosis patients.
AB  - We analyzed the effects of glatiramer acetate (GA) therapy on in vitro
      proliferative responses and cytokine production by lymphocytes derived from
      multiple sclerosis patients receiving this therapy. We confirmed that lymphocytes
      derived from GA naive patients show a high frequency of response when initially
      exposed to GA in vitro; this frequency decreased following GA therapy. The
      frequency of lymphocytes responding to whole MBP stimulation did not change with
      GA therapy. GA- and MBP-specific T cell lines generated from these patients by
      repeated cycles of in vitro stimulation did not cross react. Some (23%) whole MBP
      reactive T cell lines did cross react with MBP peptide 83-99. The mean levels of
      interferon (IFN) gamma secretion and the mean ratio of IFN-gamma/IL-5 were lower
      for GA-reactive cell lines, derived from patients both prior to and during GA
      therapy, compared to MBP-reactive T cell lines. The proportion of IFN-gamma(+)
      cells in unfractionated lymphocyte preparations derived from the GA-treated
      patients did not differ from that found for healthy controls. Our findings
      indicate that GA-reactive T cell lines derived from GA-treated MS patients
      continue to show a relative Th2 cytokine bias consistent with a bystander
      suppressor function. GA treatment is not associated with a cytokine phenotype
      shift in the total T cell or MBP-reactive T cell populations.

PMID- 10900355
TI  - Intrathecal IgG synthesis and autoantibody-secreting cells in multiple sclerosis.
AB  - We studied intrathecal IgG synthesis and autoantibody-secreting cells in 148
      patients with possible onset symptoms of MS (POSMS) or clinically definite MS
      (CDMS). In POSMS intrathecal synthesis of IgG oligoclonal bands and abnormalities
      on T2-weighted magnetic resonance imaging were associated but the former were
      more prevalent. The cerebrospinal fluid (CSF) leukocyte count and the number of
      anti-protelipid protein antibody-secreting cells in cerebrospinal fluid (CSF)
      correlated with disease activity in POSMS. Intrathecal IgG synthesis levels and
      the number of anti-myelin basic protein antibody-secreting cells in CSF
      correlated with disease activity in CDMS. Our results support recent reports of
      pathogenetic heterogeneity and a pathogenetic role of the antibody response in
      MS.

PMID- 10900356
TI  - Antibodies to chondroitin sulfates A, B, and C: clinico-pathological correlates
      in neurological diseases.
AB  - Anti-chondroitin sulfates (ChSs) antibodies have been reported in neuropathy and
      neurodegenerative diseases. Differences in specificities may account for their
      association with different diseases. Sera from 303 neurological patients were
      tested for antibodies to ChSs A, B, C. Titers >/=51,200 were found in 16 patients
      (eight peripheral neuropathy, three motor neuron disease, four multiple
      sclerosis, one myelitis). Three patients also had anti-sulfatides antibodies,
      which in two cases cross-reacted with ChSs. By indirect immunofluorescence,
      positive sera stained nuclei on normal human peripheral nerve sections. These
      findings indicate that human anti-ChSs antibodies are broadly reactive and not
      specific to any neurological disease.

PMID- 10900357
TI  - Evidence of cerebrospinal fluid free kappa light chains in AIDS patients with
      Toxoplasma gondii encephalitis.
AB  - Cerebrospinal fluid (CSF) free light chains of kappa or lambda (FLC kappa/lambda)
      type were investigated by affinity mediated blotting technique (AMI) and ELISA in
      28 patients of which nine with AIDS and Toxoplasma gondii encephalitis (AIDS,
      TE), 11 with AIDS with or without other CNS AIDS-related opportunistic infections
      (non-TE AIDS) and eight control patients with or without inflammatory
      neurological disorders (control group). CSF restricted oligoclonal FLC bands
      either of k or lambda isotype or both were found by AMI in 18 (90%) out of 20
      AIDS patients, while a CSF pattern predominantly characterized by FkappaLC rather
      than FlambdaLC was observed in eight (88.8%) out of nine TE patients. No FLC
      components were detected in the matched sera of TE or non-TE AIDS patients or in
      the CSF and sera from control group. The anti-parasite-specific FkappaLC
      CSF/serum mean levels and the T. gondii-specific FkappaLC index values were found
      by ELISA to be significantly more elevated in TE patients when compared to non-TE
      AIDS or control group. These findings suggest that the increased production of T.
      gondii-specific FkappaLC could provide insights into pathogenesis of reactivated
      TE in immunocompromised patients and may have important diagnostic usefulness.

PMID- 10900358
TI  - Expression of the chemokine receptor CXCR3 on neurons and the elevated expression
      of its ligand IP-10 in reactive astrocytes: in vitro ERK1/2 activation and role
      in Alzheimer's disease.
AB  - Inflammatory mediators have been implicated in the pathophysiology of
      neurodegenerative diseases. Here we report the presence of the chemokine receptor
      CXCR3 and its ligand, IP-10, in normal and Alzheimer's disease (AD) brains. CXCR3
      was detected constitutively on neurons and neuronal processes in various cortical
      and subcortical regions; IP-10 was observed in a subpopulation of astrocytes in
      normal brain, and was markedly elevated in astrocytes in AD brains. Many IP-10(+)
      astrocytes were associated with senile plaques and had an apparently coordinated
      upregulation of MIP-1beta. Moreover, we showed that CXCR3 ligands, IP-10 and Mig,
      were able to activate ERK1/2 pathway in mouse cortical neurons, suggesting a
      novel mechanism of neuronal-glial interaction.

PMID- 10900359
TI  - Multiple sclerosis: pro- and anti-inflammatory cytokines and metalloproteinases
      are affected differentially by treatment with IFN-beta.
AB  - Interferon-beta (IFN-beta) has a beneficial influence on the course of multiple
      sclerosis (MS) and has become standard treatment of this disease, though its
      mechanisms of action are incompletely understood. This study examines the effect
      of IFN-beta treatment on the cytokines IL-6, TNF-alpha, IFN-gamma and IL-10; the
      metalloproteinases MMP-3, -7 and -9 and the tissue inhibitor of metalloproteinase
      1 (TIMP-1). IFN-beta treatment resulted in decreased numbers of mononuclear cells
      (MNC) secreting IL-6 and TNF-alpha and expressing mRNA of MMP-3 and MMP-9
      compared to pretreatment levels. On the contrary, numbers of IL-10 secreting MNC
      and TIMP-1 mRNA expressing were augmented during IFN-beta therapy. Whether the
      down-regulatory effects on pro-inflammatory and upregulatory effects on anti
      inflammatory molecules are a direct result of IFN-beta on the immune system or
      secondary to clinical stabilization of MS pathology induced by IFN-beta remains
      to be evaluated.

PMID- 10900360
TI  - "Allograft-inflammatory-factor-1 is upregulated in microglial cells in human
      cerebral infarctions".
AB  - Allograft inflammatory factor-1 (AIF-1) is a 17-kDa-peptide identified in rat
      cardiac allografts undergoing chronic rejection and in activated microglial cells
      in inflammatory autoimune disease of the CNS. We have investigated the expression
      of AIF-1 in 18 autopsy cases of human focal cerebral infarction. AIF-1-positive
      cells show the morphology of microglia and are CD68- but not GFAP-positive. The
      peptide is expressed at a low level in normal brain. In infarctions, activated
      microglial cells in the area of glial reaction show strongly enhanced cytoplasmic
      immunoreactivity. The density of AIF-1-expressing cells increases during the
      first three days post infarction and remains elevated until chronic cystic
      stages. The upregulation of AIF-1-immunoreactivity precedes the rise in
      expression of the S-100-protein MRP-8. We conclude that AIF-1 is a sensitive
      marker of human microglial activation not only in inflammation but also in non
      inflammatory lesions of the CNS.

PMID- 10900361
TI  - Issues in Dutch palliative care: readjusting a distorted image.
AB  - This issue presents a review of several issues in Dutch palliative care, paying
      attention to readjusting a distorted image due to the euthanasia practice in the
      Netherlands. A few articles stress the evolution of palliative care (especially
      in the UK and the Netherlands), developed palliative care services in the
      Netherlands, and new developments in the Netherlands concerning the prevention of
      euthanasia through palliative care. Also the needs concerning palliative care for
      children as well as for chronic psycho-geriatrics patients are presented. Further
      attention is paid to the organisation of palliative care, focusing at evaluative
      research on palliative support teams, caring for caregivers (experiences and
      evaluation of interventions for palliative care teams), and effects of transmural
      care on coordination and continuity of care. Finally, some articles focus on
      ethical considerations in the treatment of pain in hospice movement, ethical
      evaluation of clinical trials in palliative care, and the role of informed
      consent in palliative radiotherapy, stressing the participation of patients and
      proxies in treatment decisions. Conclusions are presented on the consequences for
      educational and counselling aspects of palliative care.

PMID- 10900362
TI  - The evolution of palliative care.
AB  - An encounter with one patient in 1948 was the catalyst for the Hospice Movement.
      The challenge to undertake appropriate pain and symptom control together with
      experience in further listening to patients in the small number of homes
      especially planned for dying people, finally came together during the 1960s as
      the impetus for the first modern hospice which opened in 1967. Since then,
      palliative care has been developing worldwide and has shown that the basic
      principles demonstrated in those early years can be interpreted in various
      cultures and with different levels of resources. Symptom control by a multi
      professional team backed by research and education of both professionals and
      public has spread both into home care and into general hospitals. The family is
      seen as the unit of care as it finds its own potential, searches for meaning and
      makes the achievements possible at the end of life.

PMID- 10900363
TI  - Palliative care: an international view.
AB  - This review article addresses first the different palliative care models
      currently in use. Studies addressing the effectiveness of the models used are
      briefly summarized. Special attention is further given to models developed and
      tested in palliative care in children. Finally, the problems and pitfalls
      encountered in evaluating palliative care services are highlighted and
      recommendations are made where further research is still warranted.

PMID- 10900364
TI  - Palliative care services in The Netherlands: a descriptive study.
AB  - In this paper several types of specialized palliative care services in The
      Netherlands are presented. These include palliative care units in homes for the
      elderly, in nursing homes, in a general hospital and in an oncology clinic. In
      addition, a description is given of private hospices and of a home specializing
      in the care of terminally ill children. Furthermore, a number of other services
      relevant to palliative care are presented, such as professional and volunteer
      services for patients dying at home. Although many different types of services
      can be distinguished, regional distribution is not always optimal. The policy of
      the Dutch government on palliative care is also discussed. This policy is
      characterized by a strong emphasis on the further integration of palliative care
      in the regular health care system.

PMID- 10900365
TI  - The prevention of euthanasia through palliative care: new developments in The
      Netherlands.
AB  - Dutch palliative care stands on the eve of important changes. Further development
      of palliative care has become part of official national health care policy. One
      of the aims is prevention of euthanasia. Through an expansion and improvement of
      palliative care facilities it is trying to rule out the possibility that future
      requests of euthanasia might be brought about through insufficient and inadequate
      palliative care. This paper focuses on these new developments in The Netherlands.
      It first discusses the recent developments with regard to euthanasia. Thereafter,
      it describes the dynamic setting of palliative care. Finally, the issue of
      prevention of euthanasia through palliative care is analyzed. With regard to this
      topic, two questions need to be carefully distinguished. On the one hand, there
      is the factual question of whether a further development of palliative care can
      prevent euthanasia, on the other hand we have the normative question of whether
      palliative care should be further developed to prevent euthanasia. Both questions
      are analyzed.

PMID- 10900366
TI  - Ethical considerations in the treatment of pain in a hospice environment.
AB  - Most people treated in hospices suffer from pain. The hospice environment offers
      them a place where they may feel safe and get rest before they die. This
      particular environment was originally created to solve the many problems terminal
      patients encountered in busy modern hospitals. However, it is clear that solving
      some problems frequently means creating new ones. For people who are about to
      complete their life's journey, a hospice is a place of care and autonomy.
      Previous losses and severe spiritual distress complicate most of the severe pain
      conditions seen in hospices. In this paper, some specific ethical problems
      encountered in hospice practice will be discussed. Patients' autonomy with all
      its advantages and disadvantages will be highlighted. Acceptance of death may
      result in an active and creative attitude. Although scientific evidence of the
      processes taking place is still lacking, the modern hospice may be seen as a
      complementary, main-stream institution contributing to the development of whole
      medicine.

PMID- 10900367
TI  - Clinical trials in palliative care: an ethical evaluation.
AB  - On first sight, clinical trials do not seem to fit well within the concept of
      palliative care. In palliative care, the needs and wishes of the patient set the
      norm while participation in experimental trials is potentially harmful for the
      patient. The dilemma seems hard to solve as optimal care for the dying and
      improvement of treatment for future patients are both imperative. Yet, the one
      seems to exclude the other. However, on closer examination it becomes less
      evident that clinical trials in palliative care confront us with an unsolvable
      dilemma. Some patients' lives may gain meaning through participation in trials
      out of solidarity with future patients. In order to clarify this, the notions of
      authenticity and hope can be illuminative.

PMID- 10900368
TI  - Informed consent in palliative radiotherapy: participation of patients and
      proxies in treatment decisions.
AB  - Informed consent is regularly discussed, but little attention has been paid to
      the daily practice of the patient participation in treatment decisions regarding
      palliative care. Therefore, an exploratory study was conducted into shared
      decision making between radiation oncologists and patients and proxies in
      interviews where decisions regarding palliative radiotherapy have to be made.
      Interviews of 6 radiation oncologists with 26 outpatients were recorded on
      audiotape. Each verbal utterance was coded with the aid of the Roter Interaction
      Analysis System (RIAS). Results indicated that in over 75% of the interviews,
      patients and proxies were not asked for their opinion regarding treatment
      decisions. Other treatment options or the option of abstaining from treatment
      were discussed in 46% of the interviews. In conclusion, in this sample informed
      consent was not a natural part of the daily practice of palliative radiotherapy.
      The question remains to what extent informed consent in palliative radiotherapy
      is realistic.

PMID- 10900369
TI  - Effects of transmural care on coordination and continuity of care.
AB  - Although health care in The Netherlands is of a high quality with strong emphasis
      on primary care and high accessibility to hospital care, care deficits may arise
      in patients with chronic complex health problems who need the attention of
      several caregivers. Because no regular coordinating centre or person exists,
      coordination of care may be deficient leading to a poor continuity of care. This
      may be particularly true for those patients being cared for by both primary and
      hospital care teams, as is the case for most terminal cancer patients. Therefore,
      a transmural home care intervention programme for terminal cancer patients was
      introduced which intended to optimize coordination of care and thereby improve
      continuity of care. This quasi-experimental study investigated the effects of
      this intervention (intervention group 79 patients) on indicators of coordination
      and continuity of care. When compared to standard care (control group 37
      patients) moderate positive effects (mainly for the nursing disciplines) on the
      various indicators of coordination and continuity of care by the transmural home
      care intervention programme were found. Future prospective studies are needed to
      further elucidate the effects of transmural care on these aspects of care.

PMID- 10900370
TI  - Evaluative research on palliative support teams: a literature review.
AB  - Sixteen studies on the effectiveness of palliative support teams were analyzed.
      It was established that in most cases uncontrolled designs with repeated
      measurements were used. The assessment methods varied strongly. However, the
      Support Team Assessment Schedule was the most frequently used instrument. Effects
      reported on patients' physical symptoms, such as pain, were for the most part
      positive. Fewer effects were reported regarding psychosocial and spiritual
      problems of patients and relatives. For instance, various studies indicated that
      feelings of anxiety did not diminish after referral to a palliative support team.
      Results about the effects on use and costs of health care services did not point
      in a clear direction. Accordingly it is unclear whether palliative support teams
      reduce or increase care consumption and costs. Given the sometimes contradictory
      findings and the small number of studies conducted, future high-quality research
      into the effectiveness of palliative support teams is needed.

PMID- 10900371
TI  - Caring for caregivers: experiences and evaluation of interventions for a
      palliative care team.
AB  - Palliative care is a fairly recent development in The Netherlands. The first
      palliative unit in a hospital setting was the Palliative Care Unit (PCU) in the
      Dr Daniel den Hoed Clinic, a specialized oncology hospital, now part of the
      Academic Hospital Rotterdam (AZR-Daniel). This PCU was designed to function as an
      academic laboratory, where palliative care concepts are being developed, put into
      practice, and evaluated. It's mission was to put the patient first in mind, heart
      and soul. Right from the start, special attention was paid to the implementation
      a system of 'care for caregivers' in order to support the staff of the PCU in
      caring for the terminally ill and to prevent burnout. A process evaluation has
      been carried out with a special focus on the effects of the implementation of the
      new unit on the wellbeing of the interdisciplinary team of caregivers during the
      first year of its existence and on the experiences with a residential training
      preceding the start of patient care activities and the weekly staff support
      meetings. In the second half of the first year, the PCU staff experienced
      increased levels of job-related stress. Most stress was attributed to
      organizational factors, related to management issues but also to lack of
      institutional support. Teamwork also contributed to stress within the
      interdisciplinary team. Direct patient care activities also had some impact on
      experienced stress levels, through a heavy work-load of complex care, a shortage
      of staff and an experienced lack of competence. While the staff support
      activities were designed to give emotional support and deal with death and
      bereavement, these issues did not arise as major problems. As a consequence, the
      staff support in the PCU was perhaps less successful than it could have been.
      However, the high stress levels of this innovative palliative team warrant
      attention. We discuss how support meetings could be a more effective way of
      caring for staff. They should be accompanied by adequate resources, a supportive
      management structure, and an extensive educational program.

PMID- 10900372
TI  - Palliative care in chronic psycho-geriatrics: a case-study.
AB  - In this case-study the relevance of psycho-social interventions for providing
      palliative care in the terminal phase of life of psycho-geriatric patients with
      functional-psychiatric co-pathology is described. The know-how, interventions and
      facilities such as available in a reactivation unit in a 'psychiatric-skilled'
      Dutch nursing home, were highly relevant to tune palliative care to the needs and
      abilities of the patient. The application of the four main-dimensions of the
      method of Dynamic System Analysis (particularly Cognitive functions,
      Psychological functions, Social context and Biology) can stimulate professionals
      to use an integral perspective both to the psycho-social needs of terminal psycho
      geriatric patients and their relatives and to the biological aspects. To
      establish the value of the DSA method for providing palliative care to psycho
      geriatric patients with functional-psychiatric co-pathology scientific research
      is recommended to determine the prognostic profile of patients who benefit most
      from an actual palliative care program.

PMID- 10900373
TI  - Special issue in honour of Eduard Kellenberger.

PMID- 10900374
TI  - Microbiology: impact on research in life sciences.
AB  - In this essay with a flavor of science history, the influence of imaging
      techniques, as compared to other research strategies, on microbiologic
      investigations is discussed. Using a few selected examples, to what degree
      microbiology became a leading science during the last 50 years in gaining
      knowledge in life sciences, particularly with regard to molecular genetics and
      more recently molecular evolution is also discussed.

PMID- 10900375
TI  - Making science in a fractal landscape.
AB  - There were times when any progress in science was associated with a social
      benefit. Public support of science was growing continuously without many
      questions being asked. These times have gone and the public asks now what science
      is good for and scientists are not yet well prepared to reply. A new social
      contract between scientists and society should be elaborated based on knowledge,
      tolerance and transparency.

PMID- 10900376
TI  - Cryosubstitution of frozen biological specimens in electron microscopy: use and
      application as an alternative to chemical fixation.
AB  - Frozen bacterial cells were low-temperature embedded after cryosubstitution at
      185K in organic solvent. Temperature elevation of cryosubstituted E. coli cells,
      when still in organic solvent, had no effect on the preservation of chromatin
      structure. The achieved stabilization was found to be established independent of
      the presence of the chemical fixative. Cryosubstitution without the use of a
      chemical fixative allows for excellent preservation of cellular ultrastructure.
      Beyond that, the approach is preferential for sensitive antigens in immuno
      electron microscopy. We conclude that low-temperature dehydration by
      cryosubstitution in organic solvents is able to form stable cross-links between
      macromolecules by hydrophobic interactions.

PMID- 10900377
TI  - Structure and mass analysis by scanning transmission electron microscopy.
AB  - In the scanning transmission electron microscope (STEM) an electron beam of a few
      angstroms diameter is raster scanned over a thin sample and the scattered
      electrons are sequentially measured for each sample element irradiated. The mass,
      the elemental composition and the structure of a protein can be simultaneously
      assessed if all detector systems of the STEM are used. Aspects affecting the
      accuracy of the mass measurement technique and the demands placed on the
      instrument's dark-field detector system are outlined. In addition, the influences
      of some sample preparation techniques are noted and the mass-loss induced at
      ambient temperatures by the incidence of 80kV electrons on various biological
      samples is reported. Finally, the importance of the STEM for the structural
      analysis of proteins is documented by examples.

PMID- 10900378
TI  - Confocal laser scanning microscopy and scanning electron microscopy of tissue Ti
      implant interfaces.
AB  - Microscopic inspection of heterogenous three-dimensional (3D) objects such as
      oral implants, or implants in general, is conventionally performed either on
      ground sections of methyl-metacrylate-embedded material, at the cellular level by
      histologic analysis of the peri-implant tissue by light microscopy (LM), or at
      the supramolecular level by transmission electron microscopy (TEM).
      Alternatively, the architecture of the tissue/implant interface is visualized by
      scanning electron microscopy (SEM). The two approaches exclude each other because
      of the sample preparation.We elaborate conditions for the non-invasive analysis
      of tissue/implant interfaces by confocal laser scanning microscopy (CLSM) in
      buffer, hoping to obtain a 3D view of fluorescently labeled tissue constituents
      at the tissue implant interface and, through subsequent SEM, of the metal
      surface. The use of water-immersion objectives, originally developed for high LM
      under physiological conditions is essential. In an exploratory approach, the
      tissue/Ti-interfaces of two retrieved dental implants were analyzed. One was a
      step-cylinder used for orthodontic anchoring and the other was an endosseous step
      screw implant retrieved after infection-related loosening prior to load. The
      adhering tissue fragments were fluorescently triple-labeled for actin,
      fibronectin, and sm-alpha-actin. Optical sections for fluorescent images and for
      the laser reflection map were registered concomitantly. This approach allowed the
      labeled structures to be located on the metal surface. Subsequently, the same
      implants were prepared for SEM of the tissue/implant interface, and upon removal
      of the adhering structures, of the underlying metal surface. Thus, specific
      proteins can be identified and their spatial architecture as well as that of the
      underlying metal surface can be visualized for one and the same implant. The
      immediate visualization after fluorescence labeling in buffer by means of water
      immersion objective lenses proved most critical.

PMID- 10900379
TI  - Structural comparison of prokaryotic and eukaryotic chaperonins.
AB  - Chaperonins are key components of the cell machinery and are involved in the
      productive folding of proteins. Most chaperonins share a common general
      morphology based in a cylinder composed of two rings of 7-9 subunits, with a
      conspicuous cavity inside the particle. Chaperonins have been classified into two
      groups according to their sequence homologies: type I, whose better known member
      is GroEL, and type II comprising the eukaryotic cytosolic CCT and the
      archaebacterial thermosome, among others. Although the basic structure of both
      chaperonin types is rather similar, there are a number of basic differences among
      them. Whereas GroEL is rather non-specific regarding its substrate, CCT is more
      specialized, and plays a fundamental role in the folding of cytoskeletal
      proteins. Another important difference is that GroEL is an homopolymer, while CCT
      is an heteromeric complex built up of eight different polypeptides. Furthermore,
      GroEL requires a cofactor (GroES) that is not present in the type II chaperonins.
      Recent studies of the structure of CCT have allowed a deeper insight into its
      function. Electron microscopic analyses have revealed a different behavior of
      this chaperonin after binding to nucleotides, respect to GroEL. The atomic
      structure of the thermosome fits into the electron microscopy reconstructed
      volume of the CCT. This fitting gives clues to compare the structural transitions
      of GroEL and CCT during the folding cycle. The different changes undergone by the
      two chaperonins suggest the existence of differences in the way they bind
      substrates and enlarge the internal cavity, as well as a different type of
      signaling between the two rings of the types I and II chaperonins.

PMID- 10900380
TI  - Shunting is a translation strategy used by plant pararetroviruses
      (Caulimoviridae).
AB  - In eukaryotes standard initiation of translation involved 40S ribosome scanning
      to bridge the distance from the cap to the initiation codon. Recently deviations
      from that rule had been described, including "internal initiation", "poly-A
      dependent translation", and "ribosome shunting". In ribosome shunting, ribosomes
      start scanning at the cap but large portions of the leader are skipped. Thereby
      the secondary structure of the shunted region is preserved. Scanning in plant
      caulimoviruses involve a small open reading frame properly spaced in front of a
      strong stem structure, and, in order to function, the small open reading frome
      has to be translated and the peptide released. This arrangement can be mimicked
      by artificial small open reading frames and stem structures. Shunting with viral
      and synthetic leaders occurs not only in plant-, but also in mammalian and yeast
      systems. Thus it responds to an intrinsic property of the eukaryotic
      translational machinery and probably acts in many cases where coding regions are
      preceded by complex leaders.

PMID- 10900381
TI  - Phage-related DNA polymorphism in dairy and probiotic Lactobacillus.
AB  - Various DNA-based methods are presently being applied for identification of
      industrial bacterial cultures including dairy starter and probiotic strains of
      Lactobacillus. The success of strain-specific identification depends on the power
      of the DNA-based methods to reveal intraspecies DNA polymorphism. This study
      reveals that all eleven arbitrarily chosen Lactobacillus rhamnosus starter,
      laboratory and probiotic strains contain Lb. rhamnosus phage Lc-Nu related
      nucleotide sequences. One of these highly homologous regions in the genome of
      phage Lc-Nu was the 2.4kb HindIII fragment, which has been sequenced. Nucleotide
      sequence analysis suggested that one side of the 2.4kb HindIII fragment encodes a
      phage Lc-Nu helicase and accordingly represents an early gene region of phage Lc
      Nu genome. Five forward and five reverse primers were derived from the nucleotide
      sequence of the 2.4kb HindIII fragment of phage Lc-Nu DNA for PCR-based
      identification of the eleven Lb. rhamnosus strains included in this study. Six
      different types of PCR product patterns were obtained. Among the patterns three
      were unique to particular Lb. rhamnosus strains. The results suggest that phage
      related DNA sequences are, surprisingly, distributed widely among the Lb.
      rhamnosus strains, and that these sequences could also be a source of DNA
      polymorphism to apply for DNA-based identification of bacterial strains. Phage Lc
      Nu related DNA homology was also found in the chromosome of Lb. casei, the
      species closely related to Lb. rhamnosus.

PMID- 10900382
TI  - Fission yeast living mitosis visualized by GFP-tagged gene products.
AB  - The fission yeast Schizosaccharomyces pombe has been used as a model organism to
      study cell cycle control and dynamic chromosome behavior during anaphase
      segregation as genetic and cytological approaches are easily amenable. To
      understand the role of gene products involved in these cellular events, it is
      important to determine intracellular localization of each gene product during the
      cell cycle. In this article, visualization in living cells of several gene
      products involved in cell cycle control and sister chromatid separation is
      described. The genes tagged with jellyfish green fluorescent protein (GFP)
      include sad1(+) (encoding a spindle pole body (SPB) protein), atb2(+) (alpha
      tubulin), mis6(+) (a kinetochore protein), eat1(+) (a novel actin-like protein
      localized in the nucleus) and cdc13(+) (a mitotic cyclin). In addition, LacI
      which is bound to a DNA segment containing LacO repeat sequences integrated near
      the centromere (cen1) is visualized. These are useful to monitor cell cycle
      events in living cells.

PMID- 10900385
TI  - Women and sleep.

PMID- 10900383
TI  - Approaches to determining membrane protein structures to high resolution: do
      selections of subpopulations occur?
AB  - Three different methods are currently used for the study of high-resolution
      structures of membrane proteins: X-ray crystallography, electron crystallography,
      and nuclear magnetic resonance (NMR) spectroscopy. Thus far, all methods combined
      have yielded a rather modest number of crystal structures that have been solved
      at the atomic level. It is hypothesized here that different methods may select
      different populations of proteins on the basis of various properties. Thus,
      protein stability may be a significant factor in the formation of three
      dimensional (3D) crystals from detergent solutions, since exposure of hydrophobic
      protein zones to water may cause structural perturbation or denaturation in
      conformationally labile proteins. This is different in the formation of two
      dimensional (2D) crystals where a protein remains protected in its native
      membrane environment. A biological selection mechanism may therefore be operative
      in that highly ordered lattices may form only if strong protein-protein
      interactions are relevant in vivo, thereby limiting the number of proteins that
      are amenable to electron crystallography. Keeping a protein in a bilayer
      environment throughout 3D crystallization maintains the lateral pressure existing
      in native membranes. This can be accomplished by using lipidic cubic phases.
      Alternatively, the hydrophobic interface of a membrane protein may be spared from
      contact with water by crystallization from organic solvents where the polar caps
      are protected in reverse micelles by using appropriate detergents. Some of the
      criteria that are useful in optimizing the various approaches are given. While
      the usefulness of complementary methods seems obvious, the results presented may
      be particularly critical in recognizing key problems in other structural
      approaches.

PMID- 10900384
TI  - The cell in absence of aggregation artifacts.
AB  - Eduard Kellenberger understood that the conventional resin-embedding, he helped
      to develop (Ryter, A., Kellenberger, E., 1958. L'inclusion au polyester pour
      l'ultramicrotomie. J. Ultrastruct. Res. , 2, 200-214), was prone to aggregation
      artifacts (Kellenberger, E., 1987. The response to biological macromolecules and
      supramolecular structures to the physics of specimen cryo-preparation. In:
      Steinbrecht, R.A., Zierold, K. (Eds.), Cryo-techniques in Biological Electron
      Microscopy, Springer, Berlin, pp. 35-63). He was instrumental in developing
      various methods to overcome this limitation, for instance, by using low
      temperature-embedding and partially hydrophilic resins (Carlemalm, E., Garavito,
      R.M., Villiger, W., 1982. Resin development for electron microscopy and an
      analysis of embedding at low temperature. J. Microstruct., 126, 123-143;
      Villiger,W., 1993. Low temperature-embedding with Lowicryl resins. In: Robards,
      A.W., Wilson, A.J. (Eds.), Procedures in electron microscopy, Wiley, Chichester,
      UK, pp. 16:7.3-16:7.6). In principle, cryo-electron microscopy of vitreous
      sections is free of any aggregation artifact since the material remains fully
      hydrated and is free of chemical fixation or staining. The method is technically
      difficult still, but recent progress has made it amenable to routine practical
      applications. We compare here electron microscopical aspects of Zea mays meristem
      cells prepared by: (1) conventional resin-embedding and sectioning; (2) low
      temperature-embedding and sectioning of freeze substituted samples; and (3) cryo
      sections of vitrified samples. The appearance of the extra-cellular space, the
      cytoplasm and the nucleoplasm are very different in conditions (1) and (3). They
      appear as compact, irregular and well delineated structures in conventional resin
      sections, whereas they are more diffuse and homogeneous in the vitreous sections.
      In the resin sections, the material seems to form a complex matrix, whereas it
      looks more like a thick soup in the vitreous sample. Low temperature-embedding
      (condition 2) shows an intermediate appearance. We suggest that regardless of the
      difference due to staining and different sectioning conditions, the other image
      differences are the consequence of aggregation artifacts in the resin-embedded
      specimens.

PMID- 10900386
TI  - Risk factors for domestic violence in pregnant women.

PMID- 10900387
TI  - Necrotizing fasciitis.

PMID- 10900388
TI  - Trichomoniasis.

PMID- 10900390
TI  - Social marketing: a new approach to improved patient care.

PMID- 10900389
TI  - The impaired physician.

PMID- 10900391
TI  - Thrombotic thrombocytopenic purpura in pregnancy.

PMID- 10900392
TI  - Association between a polymorphism of ubiquitin carboxy-terminal hydrolase L1
      (UCH-L1) gene and sporadic Parkinson's disease.
AB  - We found a novel polymorphism (S/Y18) of ubiquitin carboxy-terminal hydrolase L1
      (UCH-L1) gene a mutation of which is expected to contribute to the etiology of a
      form of familial Parkinson's disease (PD). We report the frequency of this
      polymorphism in 313 patients with sporadic PD and 302 control subjects (Japanese
      and Caucasians). The frequency of the mutant allele (Y) was significantly higher
      in Japanese control subjects (51.2%) than in Japanese PD patients (43.4%)
      (chi(2)=3.917, p=0.048<0.05). It appears that this polymorphism has a weak
      protective factor against PD in at least the Japanese population. The frequencies
      of Y allele and S/Y and Y/Y genotypes in the PD patients and the controls were
      more significantly higher in Japanese than in Caucasian population (p<0.0001). It
      seems that the role of this polymorphism in PD may be different between Caucasian
      and Japanese populations.

PMID- 10900393
TI  - Failure to find mutations in ubiquitin carboxy-terminal hydrolase L1 gene in
      familial Parkinson's disease.
AB  - Recently, a missense mutation (Ile93Met) of exon 4 in the ubiquitin carboxy
      terminal hydrolase L1 (UCH-L1) gene was identified in a German family with
      autosomal dominant Parkinson's disease (ADPD). To determine whether this mutation
      is responsible for familial Parkinson's disease (PD), we sequenced the entire
      coding region of UCH-L1 gene in nine families with ADPD. No mutations in this
      gene were found in any of the families studied. We conclude that the Ile93Met
      mutation in UCH-L1 gene is a very rare cause of familial PD.

PMID- 10900394
TI  - Hemiparkinsonism associated with the unilateral striatal necrosis: a case report.
AB  - We report a patient with hemiparkinsonism associated with unilateral striatal
      necrosis of the contralateral side. The patient was an 18-year-old woman who had
      a two-month-history of difficulty in executing skilled movements with her right
      upper extremity. Neurological examination revealed that she had cogwheel rigidity
      and bradykinesia in her right upper and lower extremities. MRI revealed a well
      delineated low signal intensity in T1-weighted and high signal intensity in T2
      weighted images in the region of the putamen on the left side. Her laboratory
      data were unremarkable and mitochondrial gene mutation studies revealed no
      abnormality. It is extremely rare to encounter a case of parkinsonism associated
      with unilateral striatal necrosis.

PMID- 10900395
TI  - From Wilhelm von Humboldt to Hitler-are prominent people more prone to have
      Parkinson's disease?
AB  - We describe Parkinsonism in prominent people, where Wilhelm von Humboldt and
      Adolf Hitler provide just two spectacular, opposing examples. In both of them,
      there is little if any evidence that the disease did influence their life
      ambitions, methods of achieving them or cognitive function in general. Thus,
      Hitler's Parkinsonism should remain a 'footnote' to history, and historians
      should acknowledge that in his last years, his trembling, his curbed posture, his
      slow walking, mask-like face and low voice did not indicate remorse, fear or
      depression as a consequence of his crimes, but were mere expressions of his
      disease which, until the end, had no impact on his intellectual skills and
      methods. The apparently higher incidence of Parkinsonism in prominent people may
      be just due to their higher visibility, or a consequence of disease-related
      personality traits (e.g. ambition, perfectionism, rigidity) which may contribute
      to becoming, e.g., a prominent authoritarian person. Perhaps even some early
      behaviour pattern (such as repressed emotions or acting in public-which could
      even increase the risk of some infection) contributes to a greater vulnerability
      for developing Parkinsonism. Further studying other prominent cases might lead us
      to better understanding of risk factors and the expression of early Parkinsonism.

PMID- 10900396
TI  - Entacapone and selegiline with L-dopa in patients with Parkinson's disease: an
      interaction study.
AB  - Both the catechol-O-methyltransferase (COMT) inhibitor entacapone and the
      monoamine oxidase B (MAO-B) inhibitor selegiline are L-dopa extenders. Both are
      used, often simultaneously, as adjuncts to L-dopa/dopa decarboxylase (DDC)
      inhibitor treatment of Parkinson's disease (PD). Their possible interactions have
      not been previously studied in a double-blind manner.We studied clinical
      response, tolerability, haemodynamics and cardiac rhythm in 16 PD patients with
      end-of-dose-type motor fluctuations. The patients' individual L-dopa/DDC
      inhibitor treatment was stabilized before the experimental treatments. This was
      followed by three consecutive, randomized, double-blind 2-week treatment periods
      with entacapone (200mg with each L-dopa dose), selegiline (10mg o.d.) or both
      entacapone and selegiline with the L-dopa/DDC inhibitor medication. Clinical
      efficacy (L-dopa test with repeated motor and dyskinesia scoring) and safety
      (orthostatic test, 24-h ambulatory ECG, haematological and clinical chemistry
      variables and adverse events) evaluations were performed before each treatment
      (control) and at the end of each treatment period.All three treatments,
      entacapone, selegiline, and entacapone+selegiline as adjunct to L-dopa/DDC
      inhibitor improved (p<0.05) clinical disability compared to L-dopa only but they
      did not differ significantly from each other. Dyskinesias increased with all the
      treatments, statistically significantly (p<0.01) with entacapone+selegiline. No
      significant differences in haemodynamics were observed between control and any of
      the experimental treatments, or between the experimental treatments in the
      orthostatic test. One patient already had symptomatic orthostatism before
      experimental treatments (control). In two other patients orthostatism emerged
      after the introduction of selegiline, and in one after every experimental
      treatment. Twenty-four-hour ECG did not show any differences in supraventricular
      or ventricular extrasystoles or heart rate between treatments. No statistically
      significant differences were observed in adverse events or in haematology and
      clinical chemistry variables. One patient treated with entacapone+selegiline
      discontinued the study due to dizziness and insomnia. Our results suggest that co
      administration of entacapone with L-dopa/DDC inhibitor, with or without
      selegiline, improves clinical disability, is safe, but may also enhance dopamine
      related adverse events to some extent in PD patients with end-of-dose type motor
      fluctuations.

PMID- 10900397
TI  - Heart rate variability in Parkinson's disease patients treated with tolcapone.
AB  - Following the introduction of tolcapone, a potent, reversible Catechol-O
      methyltransferase (COMT) inhibitor, it has been possible to optimise the
      management of Parkinson's disease (PD) patients in chronic Levodopa (L-dopa)
      therapy. The interaction between tolcapone and the endogenous metabolism of
      catecholamines points to a possible influence on autonomic cardiovascular
      function.Cardiovascular reflexes have been analysed in a group of seven PD
      patients (four males, three females; mean age 69.7years, mean disease duration
      14.1years) by means of the heart rate variability (HRV) method using a continuous
      24-h ECG (ECGD), before and after six months of treatment with tolcapone (in
      addition to L-dopa).We have observed no statistically significant differences in
      HRV parameters, nor any changes in the incidence of hyperkinetic and hypokinetic
      arrhythmias, which suggest that autonomic cardiovascular function in PD patients
      is not influenced by six months of treatment with tolcapone.

PMID- 10900398
TI  - Clinical and electromyographic examinations of Parkinsonian tremor.
AB  - Background: The clinical presentations of postural Parkinsonian tremor are
      variable and different types of tremors have been described. The aim of this
      study was to re-evaluate the clinical and electromyographic (EMG) pattern of
      different tremors in Parkinsonian patients.Methods: One hundred and ten patients
      with Parkinsonian tremor were included in the study. Patients were subdivided
      into four groups according to the presence or absence of postural tremor, in
      addition to a resting tremor and its EMG pattern. The first group consisted of
      patients without postural tremor. The second group consisted of patients with
      fast postural tremor (>7Hz). The third group consisted of patients with slow
      postural tremor with alternating EMG activity. Patients with slow postural tremor
      with synchronous EMG activity were included in the fourth group. In each limb
      position, the tremor of the most involved body part was graded on the Webster
      Tremor Scale. Surface EMG recordings of the most involved limb in all positions
      were performed.Results: Postural tremor in addition to the rest one was found in
      84% of the patients. The postural tremor was with lower amplitude than the rest
      one. The frequencies and EMG patterns of the postural tremors were different and
      correlated with some specific clinical symptoms. Patients with alternating
      postural tremor had a kinetic and intention tremor in addition.Conclusions: Four
      different subtypes of Parkinsonian tremor were found according to the presence
      and type of postural tremor. These subtypes had some differing clinical
      characteristics and probably different relationships to essential tremor.

PMID- 10900399
TI  - The pharmacokinetic and clinical effects of tolcapone on a single dose of
      sublingual apomorphine in Parkinson's disease.
AB  - Apomorphine (APO) is a potent dopamine agonist that is partially metabolized by
      catachol-O-methyl transferase (COMT). Tolcapone was the first COMT inhibitor
      available for use as adjunctive therapy to levodopa in Parkinson's disease (PD).
      In order to determine whether this compound might increase the serum area under
      the curve (AUC) of APO and whether this results in any clinical benefit, we
      administered 200mg doses of tolcapone to five fluctuating PD patients taking an
      investigational sublingual APO preparation. Serial tapping speed and gait speed
      were assessed at 15min intervals over four hours, in conjunction with APO serum
      levels, following a single dose of APO, both before and five days after starting
      tolcapone (600mg/day). Serum APO levels tended to be higher (12.6%), and clinical
      measures suggested improvement during the APO "on" period after the addition of
      tolcapone (22.5% improvement in gait speed, and 7.6% improvement in tapping
      speed), but neither reached statistical significance. Further trials, involving
      larger samples are needed to clearly establish the pharmacokinetic and clinical
      effect of tolcapone in PD patients taking APO.

PMID- 10900400
TI  - Post-vaccinic opsoclonus-myoclonus syndrome: a case report.
AB  - The opsoclonus-myoclonus syndrome is a pathological condition characterized
      mainly by involuntary myoclonic movements involving ocular, trunk and limb
      muscles associated with ataxia and other neurological signs.We describe the case
      of a 30-year-old woman who developed this syndrome 15days after anti-Rubella
      vaccination. This case suggests a possible autoimmune post-vaccinic
      etiopathogenesis of opsoclonus-myoclonus syndrome, rarely described in the
      literature.

PMID- 10900401
TI  - H reflex behavior in Parkinson's disease patients. Effect of stimulus duration.
AB  - Electrical stimulus, with duration starting at 0.1ms and gradually increasing to
      1.0ms, was used for eliciting the H reflex in 21 normal subjects and 48 patients
      with Parkinson's disease (PD). In 19 normal subjects (90.5%), the threshold for
      sensory fibers was lower than for motor fibers, and the H reflex was obtained
      before the M response for all duration stimuli. In 19 PD patients (39.6%), with
      mild or moderate rigidity (according to the motor part of UPDRS), the threshold
      for the H reflex and M response was the same or the M response threshold was
      lower in at least one of the legs for short stimulus duration (0.1-0.2ms). In 15
      PD (31.2%) patients (most of them with severe rigidity), the threshold for M
      response was lower for all stimulus duration, and it was obtained before the H
      reflex. In 14 PD (29.2%) patients, the H reflex behavior was the same as in most
      normal subjects in one or both legs.These very significant differences in the
      behavior of the H reflex in PD patients (Fisher exact test, P<0.0001) could
      possibly be explained by changes in agonist-antagonist inhibition, and could be
      used as another parameter in the clinical assessment of extrapyramidal rigidity
      in PD patients.

PMID- 10900402
TI  - Into the next millennium

PMID- 10900403
TI  - Changes in F-actin organization induced by hard metal particle exposure in rat
      pulmonary epithelial cells using laser scanning confocal microscopy.
AB  - Chronic inhalation of hard metal (WC-Co) particles causes alveolitis and the
      eventual development of pulmonary fibrosis. The initial inflammatory response
      includes a change in the alveolar epithelial cell-capillary barrier, which has
      been shown to be regulated by the state of assembly and organization of the actin
      cytoskeletal network. The objective of this study was to evaluate the effect WC
      Co particles have on F-actin organization of lung epithelial cells in an in vitro
      culture system. Rat lung epithelial (L2) cells were exposed to 5, 25, and 100
      microg/mL of WC-Co particles, as well as the individual components (Co and WC) of
      the hard metal mixture particles for 24 h. The effect on F-actin organization was
      visualized by laser scanning confocal microscopy (LSCM) following Bodipy
      Phallacidin staining. Minimal changes in the F-actin microfilaments of L2 cells
      were observed by LSCM after exposure to WC and WC-Co at 5 and 25 microg/mL, while
      at 100 microg/mL, there was a noticeable disruption in the uniform distribution
      of L2 cell F-actin microfilaments. After exposure to Co, a dose-dependent change
      in the F-actin organization of the L2 cells was observed. Little change in F
      actin assembly was observed after treatment with 5 microg/mL of Co (the
      concentration equivalent to the 5% amount of Co commonly present in 100 microg/mL
      of the WC-Co sample mixture). However, at 100 microg/mL of Co, the microfilaments
      aggregated into homogeneous masses within the cells, and a significant loss in
      the organization of L2 F-actin was observed. These dramatic alterations in F
      actin organization seen after exposure to the higher doses of Co were attributed
      to an increase in L2 cell injury as measured by lactate dehydrogenase and trypan
      blue exclusion. We conclude the pulmonary response evoked in the lung by
      inhalation of high levels of WC-Co particles is unlikely due to alterations in
      the F-actin microfilaments of lung-epithelial cells.

PMID- 10900404
TI  - Studies on the in vitro phototoxicity of the antidiabetes drug glipizide.
AB  - The phototoxic antidiabetes drug glipizide (1) is photolabile under aerobic
      conditions and UV-B light. Irradiation of a phosphate-buffered solution of 1
      under oxygen atmosphere produces 4 photoproducts as well as singlet oxygen, which
      was detected by trapping it with 2,5-dimethylfuran and by the histidine test. The
      photochemistry of 1 involves cleavage of the sulfonamine and the sulfonamine-R
      bonds. Red blood cell lysis, photosensitized by glipizide and the products of its
      aerobic photolysis were demonstrated. The photohemolysis rate was lower for 1
      than for its photoproducts. Inhibition of this process on addition of 1, 4
      diazabicyclo[2.2.2]octane (DABCO), reduced glutathione (GSH), Vitamin C, sodium
      azide, superoxide dismutase, and a-tocopherol confirmed the possibility of
      singlet oxygen, superoxide ion and free radicals participation. Furthermore, in a
      lipid-photoperoxidation test with linoleic acid the in vitro phototoxicity of
      glipizide was also verified. A low decreasing cell viability of lymphocytes and
      neutrophils was observed.

PMID- 10900405
TI  - Atractyloside nephrotoxicity: in vitro studies with suspensions of rat renal
      fragments and precision-cut cortical slices.
AB  - The consumption of plants containing atractyloside, a diterpenoid glycoside,
      causes selective proximal tubule injury leading to renal failure and death in
      humans. The underlying mechanisms responsible for its toxicity are still not well
      understood. The present study was therefore carried out to determine the
      mechanism and the exact sequence of events that lead to molecular toxic injury. A
      comparative study using renal cortical slices, suspension of freshly isolated
      renal proximal tubular fragments and glomeruli of male Wistar rat was made. These
      in vitro systems were exposed to 100-1000 mM atractyloside for 2-3 h at 37
      degrees C. Atractyloside caused a significant alteration in various toxicity
      parameters in a concentration- and time-dependent manner in renal cortical slices
      and proximal tubular fragments, but not in glomeruli. The earliest change
      following exposure to atractyloside (1000 microM) was a significant reduction of
      intracellular adenosine 5'-triphosphate (ATP) content occurring within 1 h in the
      tubules and 2 h in slices. The significant depletion of reduced glutathione (GSH)
      inhibitor of p-aminohippuric (acid) (PAH) uptake and gluconeogenesis occurred
      simultaneously following loss of cellular energy. These events were only limited
      to the renal cortical slices and proximal tubular fragments. Increased severity
      of cellular injury resulted in cytotoxicity with the significant increase in the
      leakage of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in proximal
      tubular fragments (occurring at 2 h) and renal cortical slices (occurring at 3
      h). There were, however, no alterations in oxidized glutathione (GSSG) levels or
      in the ratio of GSH/GSSG. Only limited lipid peroxidation in proximal tubular
      fragments and glomeruli was observed at atractyloside concentrations of 500
      microM and above. In all cases of toxicity, the glomeruli were unaffected.
      Pretreatment of slices or fragments with probenecid (1.0 mM) failed to completely
      abolish atractyloside toxicity. These data demonstrate dose- and time-dependent
      toxicity of atractyloside and clearly confirmed the proximal tubular fragments as
      the target tissue. Atractyloside exhibits a toxicity profile that indicates early
      alteration in mitochondrial function and consequently loss of cellular energy,
      followed by reduced metabolic function and transport processes and ultimately
      cell death. This appears to be the most likely mechanism by which atractyloside
      exerted its acute cytotoxicity. Renal cortical slices, which maintain proximal
      tubule and glomeruli in their anatomic relationship, responded similarly to
      atractyloside toxicity as the proximal tubular fragments, and might be suggested
      as the most suitable in vitro model system for studying the mechanisms of
      atractyloside toxicity as they are more likely to mirror changes seen in the
      whole organ.

PMID- 10900406
TI  - Rat cortical neuron cultures: an in vitro model for differentiating mechanisms of
      chemically induced neurotoxicity.
AB  - Various structurally unrelated chemicals [2,5 hexandione, acrylamide,
      organophosphates like mipafox, beta,beta iminodipropionnitrile (IDPN), 3
      nitropropionic acid (3-NP), potassium cyanide (KCN), paraquat, and NMDA (N-methyl
      D-apartic acid)] are known to cause degenerative damage of the peripheral or
      central nervous system. Differentiated neuronal cell cultures obtained from fetal
      rats have been used to differentiate the mechanisms underlying this type of
      neurotoxicity. Cytotoxicity as measured by a viability assay was not sensitive
      enough and had to be supplemented by further endpoints covering effects on
      cytoskeleton and on the energy state of the cells [glucose consumption,
      mitochondrial membrane potential and adenosine 5'-triphosphate (ATP)
      concentration]. Compounds like the delayed neurotoxic organophosphates, exert a
      selective direct effect on cytoskeleton elements in this model at concentrations
      distinctly below cytotoxic concentrations. Other compounds, like KCN, paraquat,
      and 3-NP selectively disrupt the balance between energy supply and demand of the
      neurons either by interacting with mitochondrial respiration or glycolysis. For
      these compounds cytoskeletal damage seemed to be secondary to the energy
      depletion. For NMDA, 2,5 hexandione and acrylamide, both mechanisms may
      contribute to the neuronal damage. In conclusion, primary cortical neuronal
      cultures of the rat are well suited to detect a neurotoxic potential and to
      differentiate its underlying mechanisms. Damage of the cytoskeleton may be
      considered as an endpoint mechanistically related to degenerative neuropathic
      effects.

PMID- 10900407
TI  - Development of prediction models for three in vitro embryotoxicity tests in an
      ECVAM validation study.
AB  - Since 1997 the National Center for Documentation and Evaluation of Alternative
      Methods to Animal Experiments, ZEBET, in Berlin, has been coordinating a
      validation study aimed at prevalidation and validation of three in vitro
      embryotoxicity tests, funded by the European Center for the Validation of
      Alternative Methods (ECVAM) at the Joint Research Center (JRC, Ispra, Italy). The
      tests use the cultivation of postimplantation rat whole embryos (WEC test),
      cultures of primary limb bud cells of rat embryos (micromass or, MM, test), and
      cultures of a pluripotent mouse embryonic stem cell line (embryonic stem cell
      test or EST). Each of the tests was performed in four laboratories under blind
      conditions. In the preliminary phase of the validation study 6 out of 20 test
      chemicals comprising different embryotoxic potential (non, weakly, and strongly
      embryotoxic) were tested. The results were used to define biostatistically based
      prediction models (PMs) to identify the embryotoxic potential of test chemicals
      for the WEC test and the MM test. The PMs developed with the results of the
      preliminary phase of the validation study (training set) will be evaluated with
      the results of the remaining 14 test chemicals (definitive phase) by the end of
      the study. In addition, the existing, improved PM (iPM) for the EST, which had
      been defined previously, was evaluated using the results of the preliminary phase
      of this study. Applying the iPM of the EST to the results of this study, in 79%
      of the experiments, chemicals were classified correctly according to the
      embryotoxic potential defined by in vivo testing. For the MM and the WEC test,
      the PMs developed during the preliminary phase of this validation study provided
      81% (MM test) and 72% (WEC test) correct classifications. Because the PM of the
      WEC test took into account only parameters of growth and development, but not
      cytotoxicity data, a second PM (PM2) was developed for the WEC test by
      incorporating cytotoxicity data of the differentiated mouse fibroblast cell line
      3T3, which was derived from the EST. This approach, which has previously never
      been used, resulted in an increase to 84% correct classifications in the WEC
      test.

PMID- 10900409
TI  - A message to the membership.

PMID- 10900408
TI  - Recombinant cell bioassays for endocrine disruptors: development of a stably
      transfected human ovarian cell line for the detection of estrogenic and anti
      estrogenic chemicals.
AB  - The ability of a variety of compounds to disrupt normal endocrine homeostasis,
      and potentially, the physiological and reproductive capacity of an organism, has
      gained worldwide attention in recent years. In an attempt to identify such
      compounds, and to examine the mechanism(s) by which they may exert their actions,
      we have constructed reporter plasmid vectors that contain the firefly luciferase
      gene under hormone-inducible control of estrogen-, androgen-, or retinoic acid
      responsive DNA enhancer elements. Transient transfection of these vectors into
      appropriate receptor-containing cell lines revealed their ability to respond to
      their respective hormones with the induction of luciferase. Here, we describe
      development and optimization of a recombinant human ovarian carcinoma (BG-1)
      line, which has been stably transfected with the estrogen responsive luciferase
      reporter plasmid. The resulting recombinant cell line (BG1Luc4E(2)) responds to
      17beta-estradiol at concentrations as low as 1 pM. The utility of BG1Luc4E(2)
      cells as a bioassay screening system for environmental estrogens was demonstrated
      by their response to known xenoestrogens, and also by the putative identification
      of two polychlorinated biphenyls (2,3',4, 4,'-tetrachlorobiphenyl and 2,2',3,5',6
      pentachlorobiphenyl) as novel estrogenic chemicals. These cell bioassay systems
      have applications for rapid screening, identification, and characterization of
      endocrine disrupting chemicals.

PMID- 10900410
TI  - Parents are the best toy.

PMID- 10900411
TI  - Role delineation study of pediatric nurse practitioners: a national study of
      practice responsibilities and trends in role functions.
AB  - INTRODUCTION: This study explored the current practice responsibilities of
      pediatric nurse practitioners (PNPs) from a national perspective Educational
      preparation, geographic region of practice, years of employment as a PNP, type of
      employment setting, and full-time versus part-time employment were examined.
      METHOD: From a randomly selected sample (N = 997), a total of 387 respondents
      returned their questionnaire, resulting in 325 usable questionnaires. RESULTS:
      Years of experience as a PNP, setting of employment, geographic region,
      prescriptive authority, and subspecialty practice were significantly related to
      various health supervision and illness-focused activities performed by PNPs, as
      well as level of management responsibility. Anticipatory guidance supervision
      continues to be an integral part of the PNP role. PNPs report that they assume
      major responsibility for the health assessment and management of children with
      common pediatric illnesses as well as chronic illnesses and conditions.
      DISCUSSION: The ability to prescribe prescription medications produced the
      greatest overall effect on PNP role activities and level of management
      responsibility. Years of experience exerted an interesting effect on role
      functions related to the overall health supervision and illness-focused
      activities in which PNPs engaged. Implications for the educational preparation of
      PNPs, the updating of national certification examinations, and planning for
      adequate numbers in the workforce to replace the cohort of retiring PNPs in the
      next 20 years are discussed.

PMID- 10900413
TI  - Assessment of growth by primary health care providers.
AB  - INTRODUCTION: Precise measurements of children are critical for accurate growth
      assessment. Many children are referred to endocrine practices in error because
      heights are obtained but plotted on length growth charts, giving the appearance
      that growth has decelerated. METHOD: In an attempt to evaluate growth assessment
      in primary care practices (PCPs), we instituted a telephone survey to gather the
      following data: (a) how often children are measured, (b) the criteria for whether
      children are measured standing or lying, (c) the methods for measuring children,
      and (d) whether measurements are plotted on growth charts and by whom. RESULTS:
      In PCPs, children were reported to be measured at every visit or only at well
      child visits. The criteria most frequently used to determine when children should
      be measured standing was "if they can stand, they are measured standing."
      Significantly more pediatric practices than family practices measured children
      standing at the correct age. Heights were most often obtained on a scale with a
      floppy arm. All but 4 practices reported that measurements on growth charts were
      plotted by the nurse or physician. DISCUSSION: Many practices had an incorrect
      policy related to obtaining measurements of length versus height. Children are
      measured with the correct equipment in only 22% of PCPs for height and 12% of
      PCPs for length. Most PCPs are diligent about plotting growth data. Clearly,
      education of personnel in PCPs is crucial so that accurate growth measurements
      can be obtained, necessary referrals can be made, and unnecessary referrals can
      be avoided.

PMID- 10900412
TI  - Evaluating health and safety knowledge of preschoolers: assessing their early
      start to being health smart.
AB  - INTRODUCTION: The purpose of this study was to establish the validity,
      reliability, and utilization of a revised and expanded Preschool Health and
      Safety Knowledge Assessment (PHASKA), an instrument evaluating health and safety
      knowledge of young children, on a diverse group of preschool children. METHODS:
      This study included 308 children (133 boys and 175 girls) ranging in age from 28
      to 80 months (M = 53.7 months). The PHASKA was administered to children at 6
      preschools and 5 health fairs on an individual basis. RESULTS: Scores on the
      PHASKA ranged from 1 to 49 (out of a possible 50 points), with a mean score of
      37.25. Ninety-seven percent of the children older than age 3 years completed the
      assessment. No significant differences attributable to gender were found.
      However, significant age group differences were found [F (7,300) = 31.09, P <
      .0001]. In general, items related to safety were learned first, followed by those
      related to hygiene, health promotion, and nutrition. DISCUSSION: Preschoolers'
      scores on the PHASKA showed significant improvement with age, supporting the
      assertion that preschoolers are ready and willing learners of health and safety
      knowledge. Children rapidly gain health and safety knowledge between 3 1/2 and 5
      1/2 years of age and master much of this content by their sixth birthday. The
      PHASKA was shown to be appropriate for determining health and safety knowledge
      scores for preschool-aged children.

PMID- 10900414
TI  - Medical assessment of children going into emergency out-of-home placement.
AB  - Approximately 500,000 children and infants go into out-of-home placement in the
      United States each year. Increased attention is being given to the health care of
      children as they enter and remain in placement. This article describes a model,
      which has been in operation for 5 years, that provides medical assessments of
      children as they enter emergency out-of-home placement. The model is a community
      partnership with the county social service department, the police department, and
      the hospital. A computerized database that contains records for each child,
      including medical findings, has been helpful in developing a profile of the
      children served and contributes to continuity of care.

PMID- 10900415
TI  - Depression in adolescents.

PMID- 10900416
TI  - New pediatric antiretroviral agents.

PMID- 10900417
TI  - More red toes.

PMID- 10900418
TI  - Fifteen years of accomplishments.

PMID- 10900419
TI  - Developing collaborative practice agreements.

PMID- 10900421
TI  - Letter & Response.

PMID- 10900420
TI  - Do pediatric nurse practitioners recognize sexual abuse?

PMID- 10900422
TI  - Questions & answers.

PMID- 10900423
TI  - Combining taxanes with radiation for solid tumors.

PMID- 10900424
TI  - Plasmid/liposome transfer of the human manganese superoxide dismutase transgene
      prevents ionizing irradiation-induced apoptosis in human esophagus organ explant
      culture.
AB  - Esophagitis is a major limiting factor in the treatment of lung cancer by
      radiation alone or in combination with chemotherapy. We have previously
      demonstrated that intraesophageal injection of manganese superoxide dismutase
      plasmid/liposome (MnSOD-PL) complex into C3H/HeNsd mice blocks irradiation
      induced esophagitis. To determine whether the human esophagus can be similarly
      transfected, normal human esophageal sections obtained from the margins of
      esophagectomy specimens from esophageal cancer patients were transfected in vitro
      with alkaline phosphatase (AlkP)-PL complex and stained for AlkP activity, and
      the percent of cells expressing AlkP was calculated. At 24 hr after transfection
      with 20 or 200 microgram of AlkP-PL complex, 55.0% and 85.8% of esophageal
      epithelial cells expressed detectable AlkP, respectively. Other sections
      transfected with MnSOD-PL complex showed transgene mRNA by nested reverse
      transcriptase-polymerase chain reaction (RT-PCR) assay and increased MnSOD
      biochemical activity for at least 96 hr after transfection. Irradiated MnSOD-PL
      complex-transfected sections demonstrated a significantly decreased percentage of
      apoptotic cells when compared to irradiated control sections. Following 1,000
      cGy, MnSOD-PL-treated samples showed 7.5 +/- 2.8% and 33.3 +/- 7.3% apoptotic
      cells at 24 and 48 hr compared to 53.6 +/- 6.9% and 59.0 +/- 13.8% for
      nontransfected controls (P < 0.0001 and P < 0.1175). After 2,000 cGy, results at
      24 and 48 hr were 25.0 +/- 7.6% and 66.9 +/- 4.9% for MnSOD-transfected sections
      compared to 65.6 +/- 4.3% and 90.0 +/- 4.1% for control sections (P < 0.0001 and
      P = 0.0353), respectively. Thus, human esophageal sections can be transfected
      with MnSOD-PL complex in vitro and thereby protected against ionizing irradiation
      induced apoptosis. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 128-137 (2000).

PMID- 10900426
TI  - Results of linear accelerator-based stereotactic radiosurgery for recurrent and
      newly diagnosed acoustic neuromas.
AB  - Stereotactic radiosurgery (SRS) is used to treat acoustic neuromas, but
      additional information is needed to firmly establish its safety and efficacy. We
      review our experience over 7 years treating 29 consecutive patients with a
      modified linear accelerator (linac) SRS system. Between August 1989 and October
      1995, 29 patients with a median age of 67 years (range 26 to 83) underwent linac
      SRS treatment. Twenty-five patients had unilateral acoustic neuromas, and four
      patients with neurofibromatosis type II had bilateral vestibular schwannoma.
      Eligibility criteria for SRS were recurrent tumors (n = 9), age >65 (n = 16), or
      patient preference (n = 6). Follow-up magnetic resonance imaging scans were
      performed on all patients. The most common presenting symptoms were hearing
      impairment (18 patients) and gait difficulties (17 patients). Ten patients were
      deaf in the affected ear prior to treatment. Doses to the periphery of the tumor
      ranged from 800 to 2,400 cGy (median 1, 600 cGy) prescribed to the 50% to 80%
      isodose line (median 80%). After a median radiographic follow-up of 49 months
      (range 4 to 110 months), 11 tumors were smaller, 17 were stable, and one had
      evidence of progression (at 41 months). The 5-year local disease control rate
      (Kaplan-Meier estimate) was 94%. Acute complications were minimal, with only two
      patients experiencing nausea and vomiting after the procedure. Long-term
      complications included new or progressive trigeminal and facial nerve deficits
      with estimated 5-year incidences of 15% and 32%, respectively. Subjective hearing
      reduction or loss occurred in 14 (74%) of the 19 patients who had useful hearing
      prior to treatment. Five patients died from unrelated causes. These results
      suggest that linac SRS provides excellent short-term tumor control rates. Since
      there was a high risk of cranial nerve neuropathy, we do not recommend using only
      computed tomography-based planning and high prescription doses. Int. J. Cancer
      (Radiat. Oncol. Invest.) 90, 145-151 (2000).

PMID- 10900425
TI  - Ionizing radiation-induced death in bovine lens epithelial cells: mechanisms and
      influence of irradiation dose rate.
AB  - We recently reported, in a series of patients receiving total body irradiation
      before transplant, an influence of dose rate (DR) on cataract formation. The aim
      of our present in vitro study was to investigate the influence of DR and the
      mechanisms of lens cell death in a bovine model. After a single fraction of 10
      Gy, delivered using low (0.05 Gy/min) or high (2 Gy/min) DR (LDR and HDR,
      respectively), cells were incubated in media supplemented with two different
      fetal calf serum (FCS) concentrations (1% and 10%). Cell proliferation was
      evaluated using Hoechst 33342 (HO) probe and cell viability, with neutral red
      probe. These fluorimetric assays used a cold light cytofluorimeter. After HO
      assay, stained cells were examined with fluorescence microscopy to evaluate the
      nuclear changes related to apoptosis. Global comparison of the mean HO
      fluorescent values observed with LDR/controls (c) vs. HDR/c revealed a
      significant difference only after 96 hr (P = 0.036). In 1% FCS conditions, the
      difference between HDR/c and LDR/c was also statistically significant at 96 hr (P
      = 0.04). Pairwise multiple comparison using values observed in 1% FCS conditions
      after 96 hr incubation showed significant difference between HDR vs. c (P =
      0.001) and HDR vs. LDR (P = 0.007). This difference, in terms of fluorescence,
      was correlated to the proportion of cells with nuclear apoptotic morphology. In
      contrast, cell viability was not influenced by DR whatever the FCS concentration
      used, from 24 to 96 hr after irradiation. We conclude that our fluorimetric
      methodology is adapted to evaluate intracellular DNA modifications and cell
      viability after x-ray irradiation. We observed that a single fraction of 10 Gy
      induces in vitro lens epithelial cell apoptosis, which is influenced by DR. In
      humans, HDR is considered more cataractogenic than LDR. Thus, we speculate that
      lens cell apoptosis could be one of the major mechanisms of radiation-induced
      cataract. Further investigations are necessary to study the other possible
      mechanisms of cataractogenesis. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 138
      144 (2000).

PMID- 10900427
TI  - Prostate brachytherapy in patients with median lobe hyperplasia.
AB  - Our aim was to document the technical and clinical course of prostate
      brachytherapy patients with radiographic evidence of median lobe hyperplasia
      (MLH). Eight patients with MLH were identified during our routine brachytherapy
      practice, representing 9% of the 87 brachytherapy patients treated during a 6
      month period. No effort was made to avoid brachytherapy in patients noted to have
      MLH on diagnostic work-up. Cystoscopic evaluation was not routinely performed.
      Postimplant axial computed tomographic (CT) images of the prostate were obtained
      at 0.5 cm intervals. Preimplant urinary obstructive symptoms were quantified by
      the criteria of the American Urologic Association (AUA). Each patient was
      contacted during the writing of this report to update postimplant morbidity
      information. There was no apparent association between the degree of MLH and
      preimplant prostate volume or AUA score. Intraoperatively, we were able to
      visualize MLH by transrectal ultrasound and did not notice any particular
      difficulty placing sources in the MLH tissue or migration of sources out of the
      tissue. The prescription isodose covered from 81% to 99% of the postimplant CT
      defined target volume, achieving adequate dose to the median lobe tissue in all
      patients. Two of the eight patients developed acute, postimplant urinary
      retention. The first patient required intermittent self-catheterization for 3
      months and then resumed spontaneous urination. MLH does not appear to be a strong
      contraindication to prostate brachytherapy, and prophylactic resection of
      hypertrophic tissue in such patients is probably not warranted. Int. J. Cancer
      (Radiat. Oncol. Invest.) 90, 152-156 (2000).

PMID- 10900428
TI  - Stereotactic radiosurgery for brain metastases: results and prognostic factors.
AB  - This study was conducted to determine prognostic factors for tumor response and
      patient survival after stereotactic radiosurgery (SRS) for brain metastasis.
      Eighty-four patients with brain metastasis underwent SRS at a single institution.
      After fixation of the head with a stereotactic frame, computed tomography
      treatment planning was performed. The metastatic lesion was treated with multiple
      arcs to a median dose of 19 Gy. Forty-seven patients (56%) had a solitary brain
      lesion. Fifty-nine patients (70%) had evidence of extracranial disease at the
      time of SRS. The median survival duration from SRS was 7 months. Sixty-three
      percent of the patients had an objective radiographic response to SRS, which in
      turn was associated with superior central nervous system control. Age, collimator
      size, number of arcs, tumor location, and histology did not influence objective
      response rates. Patients who had a solitary lesion or who received treatment
      within 2 weeks after diagnosis were more likely to have an objective response
      than were those who did not (P < 0.05). Progressive brain disease accounted for
      37% of the deaths. Nineteen patients (23%) had an in-field relapse. Four severe
      complications were attributed to SRS. This study confirms the role of SRS as an
      acceptable treatment option for patients with solitary or limited brain
      metastases. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 157-162 (2000).

PMID- 10900429
TI  - Self-assessed health-related quality of life in men who have completed
      radiotherapy for prostate cancer: instrument validation and its relation to
      patient-assessed bother of symptoms.
AB  - The purpose of this study was to develop a psychometrically reliable and valid
      questionnaire to assess the disease-specific dimensions of health-related quality
      of life (HRQOL) in the urinary function (UF), bowel function (BF), and sexual
      function (SF) domains of prostate cancer (PCa) patients treated with radiation
      therapy. Patients were given a six-page questionnaire using Likert-type questions
      assessing three HRQOL dimensions during their follow-up visits after completing
      radiotherapy. Scales created from an earlier study were utilized and tested for
      reliability and validity. In addition, we assessed the relationship between these
      dimensions and the degree to which a decreased HRQOL increases the degree to
      which patients feel bothered about their symptoms. There are two scales within
      each dimension: BF, Urgency and Daily Living; UF, Urgency and Weakness of Stream;
      SF, Interest/Satisfaction and Impotence. Internal-consistency reliability
      coefficients (Cronbach's alpha) for the proposed scales range from 0.48 to 0.92,
      and all item-scale correlations and divergence correlations validate the use of
      the scales, ranging from 0.49 to 0.89. The validity of these scales is also
      confirmed by the rising median scores with rising reported levels of patient
      perceived "bother." The different dimensions have differing quantitative
      influences on patients. We have developed a prostate-specific HRQOL instrument
      that is an adequate and suitable tool for measuring HRQOL along three distinct
      dimensions for patients who have completed radiotherapy for PCa. Psychometric
      standards for reliability and validity were met for the proposed scales.
      Moreover, positive correlations were found between these dimensions and how
      bothered patients were by their symptoms, suggesting important relationships that
      should be followed in PCa patients after radiotherapy. Certain scales have strong
      influences on patient-perceived "bothersomeness" of symptoms, such as loss of
      control of BF, urgency of BF, urgency of urination, and level of
      interest/satisfaction in sex. Compared to our earlier study on patients being
      treated with radiotherapy for PCa, this study produced very similar results. With
      some modification, the same questionnaire could be used for both groups of
      patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 163-172 (2000).

PMID- 10900430
TI  - Branchial and circulatory responses to serotonin and rapid ambient water
      acidification in rainbow trout.
AB  - Although the branchial and cardiovascular effects of serotonin (5
      hydroxytryptamine) have only partially been characterized, a physiological role
      for serotonin in the cardiorespiratory responses of fish to environmental changes
      such as reduced Ph has been suggested. Therefore, we have characterized and
      compared the effects of serotonin and a rapid reduction of Ph in the ambient
      water (from pH 8.8 to pH 4.0) on ventral and dorsal aortic blood pressures, heart
      rate, cardiac output, and arterial pH in rainbow trout, Onchorhynchus mykiss. In
      addition, the circulation in the branchial microvasculature was observed using in
      vivo epi-illumination microscopy. The fall in water Ph and injection of serotonin
      (100 nmol/kg) both increased the branchial resistance and reduced the efferent
      filamental artery (EFA) blood velocity. Nevertheless, quantitatively, the
      responses to the two stimuli were different. Although acid exposure caused a much
      more profound increase in branchial resistance compared with serotonin, the blood
      flow in the observable distal portion of the EFA was only reduced by 60% in acid
      water, while it stopped with serotonin. Regardless of the marked branchial
      resistance elevation, a constriction of the efferent filamental vasculature could
      not be seen during acid exposure, as occasionally was the case with serotonin.
      While methysergide completely abolished the serotonin-induced branchial events,
      it only modestly suppressed the acid-induced reduction of EFA blood velocity. In
      contrast, all of the systemic changes induced by serotonin and acidic water were
      insensitive to methysergide. In conclusion, acidic water and injected serotonin
      elevate the branchial resistance, but the involvement of a serotonergic component
      in the acidic response appears negligible.

PMID- 10900431
TI  - Relationships between hepatic melanogenesis and respiratory conditions in the
      newt, Triturus carnifex.
AB  - The Kupffer cells (melanomacrophages) in the livers of lower vertebrates contain
      varying quantities of melanin according to the season. Specimens of Triturus
      carnifex raised for 2 months at 6 degrees C and then transferred to water at 22
      degrees C show a rapid increase in the hepatic accumulation of the pigment. The
      Kupffer cells make up more than one fourth of the liver mass in chlorbutol
      anesthetized animals isolated for 6-7 hr in hypoxic water at 18 degrees C (to
      bring the oxygen content in a 620-mL respiratory chamber from 1.1 ppm to 0.0).
      Thus, hepatic melanin is synthesized when the newt's oxygen supply is inadequate
      to meet its metabolic needs; melanogenesis, however, requires the presence of
      oxygen and does not occur in anesthetized specimens immersed in a totally anoxic
      fluid such as paraffin oil. The intraperitoneal injection prior to hypoxic
      treatment of 1 mg/g of body weight of kojic acid (inhibitor of the enzyme
      tyrosinase which catalyzes melanin synthesis) blocks melanogenesis and doubles
      oxygen consumption. The combination of hypoxia and tyrosinase inhibition causes
      permanent damage to essential functions of the nervous system, while hypoxic
      treatment alone has no irreversible consequences. The genic expression of
      tyrosinase in hypoxia appears to be a physiological response aimed at prolonging
      survival time in anaerobiosis by lowering the metabolic level; melanin would be
      an inert subproduct of this function.

PMID- 10900432
TI  - Transition of the blastomere cell cycle from cell size-independent to size
      dependent control at the midblastula stage in Xenopus laevis.
AB  - Dissociated animal cap blastomeres of Xenopus laevis blastulae were cultured at a
      low Ca level (1 microM) from 9th to 18th cell cycle at 22 +/- 1 degrees C and
      observed by a time-lapse video recorder. Blastomeres cleaved unequally to
      increase variability in cell size as cell cycles progressed, but synchronously at
      a constant cell cycle time of about 30 min up to the 12th cleavage in diploid
      cells, and up to the 13th cleavage in haploid cells, regardless of their cell
      sizes. Thereafter, blastomeres cleaved asynchronously at varying cell cycle times
      in proportion to the inverse square of their radii. The transition from the cell
      size-independent to -dependent cell cycles occurred at the critical cell radius,
      37.5 microm for the diploid and 27.9 microm for the haploid. While the protein
      synthesis inhibitor, cycloheximide (CHX) lengthened cell cycle times two- to six
      fold, epidermal growth factor (EGF) had no significant effect on the cell cycle.
      CHX-treated blastomeres synchronously cleaved at a constant cell cycle time of 60
      min up to the 12th cleavage. Thereafter, cell cycle times became variable in
      proportion to the inverse square of radii in the presence of CHX at 0.10-0.14
      microg/ml, but to the inverse cube of radii at 0.18 microg/ml. The critical cell
      size of CHX-treated blastomeres for the transition from cell size-independent to 
      dependent cell cycles remained the same as that of untreated blastomeres.
      Frequency distributions of cell cycle times of synchronous cell cycles were
      monomodal with the peak at 30 min, except for CHX-treated blastomeres with the
      peak at 60 min. In contrast, frequency distributions of asynchronous cell cycles
      were polymodal with peaks at multiples of a unit time of 30-35 min. To explain
      these results, we propose that blastomere cytoplasm has 30-min cycles that
      repeatedly produce mitosis promoting factor (MPF) in a quantity proportional to
      the cell surface area. MPF is neutralized when it titrates a nuclear inhibitor
      present in a quantity proportional to the genome size, and sequestered in the
      nucleus. When the total amount of MPF produced exceeds the threshold required to
      titrate all of the inhibitor, mitosis is initiated.

PMID- 10900433
TI  - Pineal gland of a nocturnal bird, Indian spotted owlet, Athene brama:
      morphological and endocrine observations.
AB  - It has been reported that owls (Strigiformes) do not have a pineal gland.
      However, our light microscopy study revealed an intermediate form of
      tubulofollicular and solid-type large pineal gland in a tropical owlet, Athene
      brama. The epithelial cells forming follicles (6-8) in the distal region and the
      solid cluster of parenchymal cells of different diameters in the proximal region
      anteriorly tapered with a long cylindrical stalk and continued into commissural
      organs and choroid plexus. The intrapineal localization of perivascular nerve
      fibers and blood vessels clearly explained the sympathetic innervation as well as
      vascularization of this neuroendocrine gland. Further, electron microscopy
      revealed a developed intracellular structure of the pinealocytes with a large
      number of mitochondria, Golgi bodies, and granular as well as clear vesicles in
      the process terminals. The evidence of intrapinealocyte lipid droplets and dense
      bodies and a moderate amount of melatonin in plasma (ranging from 100-365 pg/mL)
      during different reproductive phases finally proved a defined secretory activity
      of the gland in this tropical, nocturnal bird.

PMID- 10900434
TI  - Involvement of purines and phosphoinositides in spontaneous and progesterone
      induced nuclear maturation of Bufo arenarum oocytes.
AB  - Although progesterone is the established maturation inducer in amphibia, it has
      been demonstrated that Bufo arenarum oocytes resume meiosis with no need of an
      exogenous hormonal stimulus if deprived of their enveloping follicle cells, a
      phenomenon called "spontaneous maturation." The present studies were designed to
      evaluate the participation of purines and phosphoinositides in the spontaneous
      and progesterone-induced maturation in Bufo arenarum full-grown oocytes. The
      presented data demonstrate that high intracellular levels of purines such as cAMP
      or guanosine can inhibit both spontaneous and progesterone-induced maturation in
      full-grown denuded Bufo arenarum oocytes. Moreover, the fact that the
      mycophenolic acid was able to induce maturation in denuded oocytes obtained
      during the nonreproductive period in a manner similar to that of the progesterone
      and also to increase the percentages of spontaneous maturation suggests that in
      Bufo arenarum, inosine monophosphate dehydrogenase inhibition is an important
      step in the resumption of meiosis. Inhibition of the phosphatidylinositol 4,5
      bisphosphate hydrolysis by treatment of denuded oocytes with neomycin totally
      blocks spontaneous and progesterone-induced maturation, suggesting that the
      products of this hydrolysis (1,2 diacylglycerol and inositol 1,4,5 trisphosphate)
      may be involved in the maturation process of Bufo. In addition, our results
      indicate that the activation of protein kinase C is also involved in both types
      of maturation.

PMID- 10900435
TI  - Environmental factors affecting sexual differentiation in the entomopathogenic
      nematode Heterorhabditis bacteriophora.
AB  - The present study was aimed at determining the influence of various environmental
      factors on sex differentiation (SD) in the entomopathogenic nematode
      Heterorhabditis bacteriophora HP88 strain, under in vivo and in vitro culture
      conditions. Injection of individual nematodes into last instars of Galleria
      mellonella resulted in development of a similar number of females and
      hermaphrodites (35-40%) and 20-25% males. Increasing the number of nematodes
      injected into the insect did not change these proportions. In smaller insects
      (0.7-1.5 cm long), an increase in the proportion of hermaphrodites was recorded
      as compared with larger size cadavers (2.4-2.7 cm long). When individual
      hermaphrodites were placed on NGM, the proportion of hermaphrodites, females and
      male progeny was 63%, 31%, and 6%, respectively. Rearing on richer medium ("Dog
      food" agar) resulted in reduction in the proportion of hermaphrodites. Nematodes
      introduced to the symbiotic bacterium obtained from other nematode strains (IS-5
      and IS-33) developed similarly to the culture reared on the HP88 bacteria.
      Rearing the nematodes at a temperature range between 21 degrees C to 30 degrees C
      also did not have a significant effect on the sexual differentiation among
      nematodes cultured on NGM. The proportion of hermaphrodites increased as the
      starvation period of hatching nematode juveniles lengthened (>6 hr). The data
      obtained in the present study strongly suggest that the main factor affecting sex
      differentiation in H. bacteriophora is the nutrition source. The practical and
      biological implications of the results are discussed.

PMID- 10900436
TI  - Morphological and functional variations of Leydig cells in testis of the domestic
      pig during the different biological stages of development.
AB  - The relationship of morphometrical and androgen receptor evaluations of the main
      testicular interstitium cellular element (Leydig cells) in the domestic pig
      provided interesting numerical and morphological features during the different
      aging stages. As early as 25 days (a period in which the pig is sexually
      immature) there was a low number of Leydig cells (1.46 x 10(8)) with respect to a
      78% and 35% increase in the adult (2.48 x 108) and aged (1.78 x 10(8)) animal,
      respectively. Interestingly, when the volume density of Leydig cells was
      considered, the average volume of these cells seemed to be high (75%) in the aged
      pig with respect to the young immature animal whereas a lower increase (27%) was
      observed for the adult animal. Moreover, the evaluation of testosterone receptor
      binding sites in the testis at the various stages of development also displayed a
      differentiated pattern since elevated testosterone receptor binding levels of the
      high dissociation affinity type were obtained for the adult pig. Thus, from the
      combined morphological variations of Leydig cells and testosterone receptor
      binding activity, it appears that this androgenic receptor component exerts
      distinct autocrine effects on the different functional features of some
      testicular tissue constituents at the different aging stages of the domestic pig.

PMID- 10900437
TI  - Postovulatory follicle: a model for experimental studies of programmed cell death
      or apoptosis in teleosts.
AB  - This is the first evidence of programmed cell death, or apoptosis, occurring in
      the postovulatory follicle (POF) of teleost fish. Females of Astyanax bimaculatus
      lacustris were submitted to induced ovulation through injecting pituitary
      extract. Ultrastructural analyses of POFs at time intervals varying from zero to
      four days postspawning showed several characteristic events of the apoptosis.
      Typical apoptotic figures, such as nucleus with chromatin condensation underlying
      the nuclear envelope in a crescent pattern and apoptotic bodies at different
      stages of formation and reabsorption, were observed in the follicular cells a few
      days after the onset of the postovulatory period. The results indicated that
      apoptosis is the major mechanism responsible for the elimination of the
      follicular cells in the POFs of A. bimaculatus lacustris during ovarian recovery
      postspawning. It is suggested that POFs might be used as an experimental model in
      dynamic studies involving cell death in teleosts.

PMID- 10900438
TI  - Avian galanin: cloning of complementary DNAs and characterization of transcripts
      in different tissues.
AB  - Avian galanin was first isolated from the chicken intestine, and subsequently
      from the quail oviduct. Avian galanin is a 29-residue peptide including an
      amidated threonine at the C-terminus and differs at several positions from the C
      terminal part of mammalian galanins. In contrast to extensive mammalian studies,
      no information is available on the structure of precursor molecule of avian
      galanin. In this study, therefore, we conducted complementary DNA (cDNA) cloning
      of the avian galanin gene from quail brain RNA using degenerated 3'RACE and
      5'RACE techniques. A cloned cDNA for avian galanin contained an open reading
      frame consisting of 117 amino acids which had overall amino acid homology of 63%,
      60%, 54%, 58%, and 62% with bovine, human, mouse, porcine, and rat galanins,
      respectively. Another cDNA containing a 69-nucleotide insertion, which gave an
      additional 23 amino acids to mature avian galanin, was also cloned, suggesting
      the presence of two transcripts by alternative splicing. Northern blot analysis
      revealed that avian galanin mRNA was expressed, as a shorter transcript, in the
      quail brain, ovary, and intestine, unlike the liver and oviduct. A larger mRNA of
      avian galanin may be further expressed only in the ovary.

PMID- 10900439
TI  - Melanosome and erythrosome positioning regulates cAMP-induced movement in
      chromatophores from spotted triplefin, Grahamina capito.
AB  - This study investigated regulation of uniform positioning of melanosomes and
      erythrosomes in chromatophores from spotted triplefin Grahamina capito from New
      Zealand, by modulating levels of intracellular cAMP. Elevated cAMP levels, caused
      by forskolin treatment, inhibited aggregation and induced rapid dispersion of
      melanosomes and erythrosomes. The dispersing organelles moved to and accumulated
      at the cell periphery, leading to an abnormal hyperdispersed state with a
      melanosome- or erythrosome-depleted cell center. Minutes after hyperdispersion,
      these organelles reversed direction and moved towards the center again to finally
      distribute throughout the cells. When chromatophores with initially dispersed
      melanosomes or erythrosomes were treated with forskolin, no hyperdispersion was
      seen, but the erythrosomes aggregated slowly. Disassembly of actin by latrunculin
      resulted in a similar but constant hyperdispersed melanosome and erythrosome
      distribution. The results show that cAMP not only disperses but also aggregates
      melanosomes and erythrosomes, and that it is the intracellular position of these
      organelles that determine the directionality of the cAMP-induced movement. To
      ascertain the even distribution in the dispersed state, regulatory components
      associated with the actin cytoskeleton in the cell periphery might modify
      activity of cytoplasmic dynein or kinesin upon contact with dispersing
      melanosomes or erythrosomes.

PMID- 10900440
TI  - Cloning and characterization of salmon hsp90 cDNA: upregulation by thermal and
      hyperosmotic stress.
AB  - Accumulating evidence suggests that glucocorticoids are essential for development
      of hypoosmoregulatory capacity in salmon during adaptation to seawater. Heat
      shock protein (hsp)90 has been reported to function in signal transduction and
      the maturation and affinity of glucocorticoid receptors. We sought to determine
      whether this hsp might be upregulated by thermal and hyperosmotic stress in
      salmon, a species that migrates between the freshwater and marine environments. A
      2625-bp cDNA cloned from a salmon cDNA library was found to code for a protein of
      722 amino acids exhibiting a high degree of identity with zebra fish (92%) and
      human (89%) hsp90beta. Accumulation of hsp90 mRNA was observed in isolated
      branchial lamellae incubated under hyperosmotic conditions and in branchial
      lamellae of salmon exposed to hyperosmotic stress in vivo. In contrast, exposure
      of kidney to hyperosmotic stress in vitro and in vivo failed to elicit an
      increase in the quantity of hsp90 mRNA. By way of comparison, accumulation of
      hsp90 mRNA was observed in both branchial lamellae and kidney tissue subjected to
      thermal stress in vitro and in vivo. Western blot analyses of proteins isolated
      from tissues under identical conditions in vitro revealed that the pool of hsp90
      increased with thermal stress but not with osmotic stress. The results suggest
      that accumulation of hsp90 mRNA in response to osmotic stress is unrelated to
      cellular protein denaturation and that synthesis of hsp90 may be regulated at
      both the level of transcription and translation.

PMID- 10900441
TI  - Secretory activity of gonadotropin and the responsiveness of gonadotrophs to
      gonadotropin-releasing hormone during the annual reproductive cycle of male bats,
      Rhinolophus ferrumequinum: analysis by cell immunoblot assay.
AB  - The purpose of this study was to examine secretory activity of gonadotropin (Gn)
      and the responsiveness of Gn secretion to Gn-releasing hormone (GnRH) in male
      horseshoe bats, Rhinolophus ferrumequinum, during the annual reproductive cycle.
      Anterior pituitary cells were monodispersed and subjected to cell immunoblot
      assay for Gn. Cell blots specific for follicle stimulating hormone (FSH) or
      luteinizing hormone (LH) were quantified using a microscopic image analyzer. The
      percentages of LH- or FSH-secreting cells detected as immunoreactive cell blots
      were markedly increased in the spermatogenic period (summer) and decreased in the
      hibernation period (winter). The mean Gn secretion from individual cells and
      total Gn secretion per unit area of the transfer membrane also showed similar
      changes. The responsiveness of Gn secretion to GnRH was greater in the
      spermatogenic period than in other seasons. On the other hand, although the
      secretory activity of Gn was markedly decreased during hibernation, a stimulatory
      effect of GnRH on Gn secretion was observed. These findings suggest that seasonal
      changes in the release of Gn required for gametogenesis and gonadal
      steroidogenesis varied depending on the reproductive activity and seasonal
      changes in Gn sensitivity to stimulatory effects of GnRH due to alterations in
      GnRH receptor numbers and/or in postreceptor events of gonadotrophs.

PMID- 10900442
TI  - Evidence of temperature-dependent sex determination in the European sea bass
      (Dicentrarchus labrax L.).
AB  - To test the hypothesis that sex determination in the European sea bass
      (Dicentrarchus labrax L.) Can be affected by the incubating temperature during
      the very early developmental stages, eggs from the same batch of spontaneously
      spawned broodstock were divided at the stage of half-epiboly into three groups
      according to rearing temperature: G13 = 13 degrees C, G15 = 15 degrees C, and G20
      = 20 degrees C. Temperature treatment lasted until the middle of metamorphosis
      (17-18 mm total length, [TL]), and, with the exclusion of water temperature, all
      biotic and abiotic conditions were identical for the three experimental groups.
      The on-growing phase was performed under ambient photoperiod and temperature
      conditions for all groups. Sex proportions were determined by histological
      examination of the gonads of fish at 308, 467, and 568 days posthatch (DPH). At
      308 DPH (TL: 135-201 mm), 100% of the specimens had differentiated into males and
      females. A significantly higher (P < 0.01) proportion of females was found in
      groups G13 (72-74%) and G15 (67-73%) than in group G20 (24-28%). At the final
      sampling there was no statistically significant difference in body weight between
      the experimental groups. However, in all groups, female fish were larger than
      males (P < 0.001). Results provide for the first time clear evidence that
      temperature during the very early developmental stages is the crucial factor
      affecting the process of sex differentiation of the sea bass, with low rearing
      temperatures (13 or 15 degrees C) resulting in sex proportions consistently
      skewed in favor of females.

PMID- 10900443
TI  - Origin of germ cells, sex determination, and sex inversion in medusae of the
      genus Clytia (Hydrozoa, leptomedusae): the influence of temperature.
AB  - In Cnidaria, a separation between soma and germline remains unclear. In this
      work, we studied the origin of germinal cells and determination of the sexual
      phenotype in Clytia hemisphaerica and Clytia sp. Colonies of C. Hemisphaerica
      were cultivated and the medusae liberated by each colony raised until maturity.
      Two hermaphrodite colonies were obtained, liberating male and female medusae.
      These two colonies and their medusae were raised at 15 degrees C, 21 degrees C,
      or 24 degrees C. The medusae budded and cultured at 24 degrees C were mainly
      female (80%). In contrast, if the medusae were released at 15 degrees C, at
      whatever temperature they were raised later, they were mainly male (85%). The
      same occurred if, after release at 24 degrees C but before the formation of the
      gametes, they were kept at 15 degrees C for at least 24 hr. We suggest that there
      are two subpopulations of germ cells. The female line will be dominant at 24
      degrees C but temperature sensitive, with inhibition of this line by a
      temperature drop to 15 degrees C, this inverting the population sex-ratio. The
      irreversible action of a temperature drop to 15 degrees C supports the view that
      the germ cells are isolated very early. In C. hemisphaerica, hermaphrodite
      medusae were never observed. On the contrary, in Clytia sp., probably a new
      species, we have found male, female, but also hermaphrodite specimens. This is
      the second definite example of hermaphroditism described in any hydromedusan. The
      transformation of female into hermaphrodite then into male specimens occurs at 13
      degrees C. These results demonstrate the unstable character of genetic sex
      determination in cnidarians, at least in certain species.

PMID- 10900445
TI  - The impact of covariate imbalance on the size of the logrank test in randomized
      clinical trials.
AB  - This paper examines the baseline imbalance incidental to stratified random
      sampling in clinical trials. We assume that patients are randomly sampled from a
      stratum-specific population and assigned to either treatment or control groups.
      Prognostic factors not used for the stratification cause within-stratum patient
      heterogeneity. The patient heterogeneity is investigated with an analysis of the
      prognostic index, or the log-relative-hazard. An index V, used to measure the
      degree of baseline imbalance between the groups, is defined using the prognostic
      index. The degree of baseline imbalance resulting from the stratified random
      sampling of a population of heterogeneous patients is examined. A method to
      estimate the exact size of the stratified logrank test is developed and applied
      to data obtained from a cancer clinical trial.

PMID- 10900444
TI  - Multiple triggers of oocyte maturation in nemertean worms: the roles of calcium
      and serotonin.
AB  - To analyze the process of oocyte maturation in nemertean worms, oocytes with a
      large nucleus (=germinal vesicle, or GV) were removed from gravid ovaries of
      Cerebratulus lacteus and Micrura alaskensis. Following transfer to natural
      seawater (NSW), fully grown oocytes spontaneously matured as indicated by their
      completion of germinal vesicle breakdown (GVBD), whereas GVBD was reversibly
      blocked if the oocytes were initially placed in calcium-free seawater (CaFSW).
      Similarly, calcium ionophore treatments triggered GVBD in calcium-containing
      artificial seawater (ASW) but not in CaFSW, suggesting that external calcium
      influx may facilitate maturation. However, compared to the overall levels of
      maturation elicited by ASW, significantly higher percentages of GVBD were
      achieved with NSW or with ASW that had been conditioned with marine sediment.
      Moreover, calcium channel blockers decreased GVBD rates in ASW but not in NSW,
      which is consistent with the view that substances other than external calcium
      ions can trigger maturation. Accordingly, oocytes underwent equally high levels
      of GVBD when treated with serotonin (=5-hydroxytryptamine, or 5-HT) in ASW or
      CaFSW. The 5-HT-induced maturation was blocked by inhibitors of 5-HT receptors
      but continued to occur in the presence of calcium channel blockers or the calcium
      chelator BAPTA. In addition, oocytes microinjected with fluorescent calcium
      indicators underwent GVBD in response to 5-HT without displaying marked calcium
      transients during confocal imaging runs. Collectively, such findings suggest that
      nemertean oocytes can mature via multiple pathways that may include external
      calcium influx or a 5-HT-induced signaling cascade that lacks prominent calcium
      fluctuations. J. Exp. Zool. 287:243-261, 2000.

PMID- 10900446
TI  - Linear discriminant models for unbalanced longitudinal data.
AB  - This paper discusses statistical methods for the classification of observations
      into one of two or more groups based on longitudinal observations. Measurements
      on subjects in longitudinal medical studies are often collected at different
      times and on a different number of occasions. Classical multivariate methods for
      linear discriminant analysis are difficult to apply to repeated measurements due
      to the highly unbalanced structure observed in these data. Linear models for the
      analysis of longitudinal data proposed by Laird and Ware and non-linear models
      proposed by Lindstrom and Bates can be used to estimate population parameters for
      a discriminant model that classifies individuals into distinct predefined groups
      or populations. An example is presented using data from a study in 150 pregnant
      women in Santiago, Chile, in order to predict normal versus abnormal pregnancy
      outcomes.

PMID- 10900447
TI  - Designing cancer prevention trials: a stochastic model approach.
AB  - There is growing interest in the design and implementation of cancer prevention
      trials. The key idea is to have agents which interfere with carcinogenesis and/or
      the preclinical stage. In this article we develop multi-stage stochastic models
      for the planning of cancer prevention trials. For known inputs it is possible to
      calculate the incidence of disease for the control and intervention groups.
      Consequently we find designs that balance the required sample size and follow-up
      time while guaranteeing prespecified error probabilities. Moreover such models
      can incorporate the mode of action of the intervention as well as compliance. The
      model has been applied to breast cancer to determine the implications for
      planning breast cancer intervention trials. Although the model addresses issues
      in cancer prevention, it is quite general and may be suitable for other chronic
      diseases.

PMID- 10900448
TI  - Comparing tumour staging and grading systems: a case study and a review of the
      issues, using thymoma as a model.
AB  - We consider the problem of comparing alternative cancer staging and grading
      systems. Statistical comparisons are on the basis of the ability to predict
      survival, but more qualitative criteria, such as parsimony, and distinctive
      prognostic separability of the categories are relevant also. Furthermore, some
      staging systems are clearly ordinal, while others are not. Three candidate
      statistical measures are studied and compared: explained variation; area under
      the ROC curve; and the probability of concordance of stage and survival. Each of
      these has individual strengths and weaknesses. A data set involving the staging
      of thymoma is analysed in detail to motivate the problem and illustrate the
      results.

PMID- 10900449
TI  - Spatio-temporal interaction with disease mapping.
AB  - Markov chain Monte Carlo methods are used to estimate mortality rates under a
      Bayesian hierarchical model. Spatial correlations are introduced to examine
      spatial effects relative to both regional and regional changes over time by
      groups. A special feature of the models is the inclusion of longitudinal
      variables which will describe temporal trends in mortality or incidences for
      different population groups. Disease maps are used to illustrate the role of
      different parameters in the model and pinpointing areas of interesting patterns.
      The methods are demonstrated by male cancer mortality data from the state of
      Missouri during 1973-1992. Of special interest will be the geographic variations
      in the trend of lung cancer mortality over the recent past. Marginal posterior
      distributions are used to examine effects due to spatial correlations and age
      difference in temporal trends. Numerical results from the Missouri data show that
      although spatial correlations exist, they do not have a large effect on the
      estimated mortality rates.

PMID- 10900450
TI  - First steps in analysing NHS waiting times: avoiding the 'stationary and closed
      population' fallacy.
AB  - The aim of this paper is to demonstrate the effect of excluding incomplete
      observations and competing events when calculating cross-sectional measures of
      NHS waiting times, and to obtain a more accurate estimate of the 'time-to
      admission' of those listed on NHS waiting lists using life-table methods. The
      official 'times-since-enrollment' of all elective 'admissions' in England, 1 July
      to 31 December 1994 inclusive, were extracted from Hospital Episode Statistics.
      The official 'times-to-census' of all those on a waiting list in England at 30
      September 1994 were obtained from aggregated KH07 data. The percentage waiting at
      least three months, at least six months etc., was calculated separately for each
      data set and compared with a period life-table derived from the combined data.
      The cumulative likelihood of elective admission is markedly overestimated across
      the whole range of waiting times. The experience of those still waiting, those
      removed from the list, those suspended or deferred and those put to the back of
      the queue is not taken into account in the calculation of official waiting times.
      The Department of Health currently presents the 'time-since-enrollment' of those
      admitted as though it indicates how long all patients can expect to wait for
      admission. The consequent bias in published summary statistics incorrectly
      quantifies the real experience of patients. It is recommended that calculation of
      waiting times from KH07 census counts and Hospital Episode Statistics be
      reconsidered in the light of what patients, clinicians, managers and politicians
      need to know about treatment delay.

PMID- 10900451
TI  - A useful monotonic non-linear model with applications in medicine and
      epidemiology.
AB  - In medicine and epidemiology monotonic curves are important as models for
      relations which prior knowledge or scientific reasoning dictate should increase
      or decrease consistently with the predictor value. An example is the
      monotonically increasing relation between cigarette consumption and the risk of
      coronary heart disease. In this paper I propose a new class of monotonic non
      linear models which generalizes the well-known power and exponential
      transformations of a covariate. The models are cousins of the Gompertz family of
      growth curves and include non-sigmoid and asymmetric sigmoid curves. I explore
      their properties and illustrate their usefulness in three substantial medical and
      epidemiological data sets.

PMID- 10900452
TI  - Analysis of time trends in adaptive designs with application to a neurophysiology
      experiment.
AB  - Time trends are present in many sequential experiments. Adaptive designs use
      accruing data to select future design points. It has been observed that the
      presence of time trends in adaptive designs can bias results of the study. We
      propose one method of dealing with time trends in analysing adaptive designs. The
      method, relevance weighted likelihood, weights individual components of the
      likelihood differently. Consequently, one can downweight earlier data if there is
      a clear time trend that converges at some point in the study. We apply this
      methodology to a data set from an adaptive design in neurophysiology. We find
      that the method is robust and useful in getting more precise estimates of an
      individual subject's median response.

PMID- 10900454
TI  - Proteome profiling-pitfalls and progress.
AB  - In this review we examine the current state of analytical methods in proteomics.
      The conventional methodology using two-dimensional electrophoresis gels and mass
      spectrometry is discussed, with particular reference to the advantages and
      shortcomings thereof. Two recently published methods which offer an alternative
      approach are presented and discussed, with emphasis on how they can provide
      information not available via two-dimensional gel electrophoresis. These two
      methods are the isotope-coded affinity tags approach of Gygi et al. and the two
      dimensional liquid chromatography-tandem mass spectrometry approach as presented
      by Link et al. We conclude that both of these new techniques represent
      significant advances in analytical methodology for proteome analysis.
      Furthermore, we believe that in the future biological research will continue to
      be enhanced by the continuation of such developments in proteomic analytical
      technology.

PMID- 10900455
TI  - Yeast two-hybrid systems and protein interaction mapping projects for yeast and
      worm.
AB  - The availability of complete genome sequences necessitates the development of
      standardized functional assays to analyse the tens of thousands of predicted gene
      products in high-throughput experimental settings. Such approaches are
      collectively referred to as 'functional genomics'. One approach to investigate
      the properties of a proteome of interest is by systematic analysis of protein
      protein interactions. So far, the yeast two-hybrid system is the most commonly
      used method for large-scale, high-throughput identification of potential protein
      protein interactions. Here, we discuss several technical features of variants of
      the two-hybrid systems in light of data recently obtained from different protein
      interaction mapping projects for the budding yeast Saccharomyces cerevisiae and
      the nematode Caenorhabditis elegans.

PMID- 10900456
TI  - Genome-wide protein interaction screens reveal functional networks involving Sm
      like proteins.
AB  - A set of seven structurally related Sm proteins forms the core of the snRNP
      particles containing the spliceosomal U1, U2, U4 and U5 snRNAs. A search of the
      genomic sequence of Saccharomyces cerevisiae has identified a number of open
      reading frames that potentially encode structurally similar proteins termed Lsm
      (Like Sm) proteins. With the aim of analysing all possible interactions between
      the Lsm proteins and any protein encoded in the yeast genome, we performed
      exhaustive and iterative genomic two-hybrid screens, starting with the Lsm
      proteins as baits. Indeed, extensive interactions amongst eight Lsm proteins were
      found that suggest the existence of a Lsm complex or complexes. These Lsm
      interactions apparently involve the conserved Sm domain that also mediates
      interactions between the Sm proteins. The screens also reveal functionally
      significant interactions with splicing factors, in particular with Prp4 and
      Prp24, compatible with genetic studies and with the reported association of Lsm
      proteins with spliceosomal U6 and U4/U6 particles. In addition, interactions with
      proteins involved in mRNA turnover, such as Mrt1, Dcp1, Dcp2 and Xrn1, point to
      roles for Lsm complexes in distinct RNA metabolic processes, that are confirmed
      in independent functional studies. These results provide compelling evidence that
      two-hybrid screens yield functionally meaningful information about protein
      protein interactions and can suggest functions for uncharacterized proteins,
      especially when they are performed on a genome-wide scale.

PMID- 10900458
TI  - Website review: The Jackson Laboratory Mouse Genome Informatics Site: version
      2.3.2.
AB  - Site authors: Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor,
      Maine. Project PI: Janan Eppig. All screen views from the website are reproduced
      with the kind permission of Janan Eppig.

PMID- 10900457
TI  - Comparative genomics uncovers large tandem chromosomal duplications in
      Mycobacterium bovis BCG Pasteur.
AB  - On direct comparison of minimal sets of ordered clones from bacterial artificial
      chromosome (BAC) libraries representing the complete genomes of Mycobacterium
      tuberculosis H37Rv and the vaccine strain, Mycobacterium bovis BCG Pasteur, two
      major rearrangements were identified in the genome of M. bovis BCG Pasteur. These
      were shown to correspond to two tandem duplications, DU1 and DU2, of 29 668 bp
      and 36 161 bp, respectively. While DU1 resulted from a single duplication event,
      DU2 apparently arose from duplication of a 100 kb genomic segment that
      subsequently incurred an internal deletion of 64 kb. Several lines of evidence
      suggest that DU2 may continue to expand, since two copies were detected in a
      subpopulation of BCG Pasteur cells. BCG strains harbouring DU1 and DU2 are
      diploid for at least 58 genes and contain two copies of oriC, the chromosomal
      origin of replication. These findings indicate that these genomic regions of the
      BCG genome are still dynamic. Although the role of DU1 and DU2 in the attenuation
      and/or altered immunogenicity of BCG is yet unknown, knowledge of their existence
      will facilitate quality control of BCG vaccine lots and may help in monitoring
      the efficacy of the world's most widely used vaccine.

PMID- 10900460
TI  - Meeting review: the Drosophila genome: so that's what it looks like!

PMID- 10900459
TI  - Featured organism: Drosophila melanogaster.

PMID- 10900462
TI  - The proprotein convertases furin and PACE4 play a significant role in tumor
      progression.
AB  - Processing of latent precursor proteins by proprotein convertases (PCs) into
      their biologically active products is a common mechanism required for many
      important biologic functions. This process is tightly regulated, leading to the
      generation of active peptides and proteins including neuropeptides and
      polypeptide hormones, protein tyrosine phosphatases, growth factors and their
      receptors, and enzymes including matrix metalloproteases (MMPs). These processing
      reactions occurs at pairs of basic amino acids. Within the past several years, a
      novel family of Ca(2+)-dependent serine proteases has been identified, all of
      which possess homology to the endoproteases subtilisin (bacteria) and kexin
      (yeast). This family of PCs is currently comprised of fewer than a dozen members,
      known as furin/paired basic amino-acid-cleaving enzyme (PACE), PC1/PC3, PC2, PC4,
      PACE4, PC5/PC6, and PC7/PC8/lymphoma proprotein convertase. They share a high
      degree of amino-acid identity of 50-75% within their catalytic domains. Despite
      the relatively high degree of homology in the PC family, only PACE4 and furin
      localize to the same chromosome: mouse chromosome 7 and human chromosome 15.
      Recent reports have supported a possible functional role for PCs in
      tumorigenesis. For instance, convertases have been shown to be expressed in
      various tumor lines and human primary tumors. Furin and PACE4 process stromelysin
      3 (MMP-11 or Str-3), an MMP involved in tumor invasion, into its mature, active
      form. Similarly, a growing family of MMPs, known as membrane-type
      metalloproteinases (MT-MMPs), and growth factors and adhesion molecules such as E
      cadherin show similar amino-acid motifs and thus could be activated by furin and
      PACE4. These data, taken together with the high expression levels of PACE4 in 50%
      of murine chemically induced spindle cell tumors, confer to PACE4 and possibly
      other PCs a possible functional role in the activation of MMPs and consequently
      in tumor cell invasion and tumor progression. This was further supported by the
      remarkable enhancement in the invasive ability of the PACE4-transfected murine
      tumor cell lines. Mol. Carcinog. 28:63-69, 2000.

PMID- 10900463
TI  - Endometrial stromal cells regulate gap-junction function in normal human
      endometrial epithelial cells but not in endometrial carcinoma cells.
AB  - Gap junctions are transmembrane proteins comprised of six connexin subunits that
      facilitate direct solute transport between adjacent cells through gap junctions.
      Previous studies from other laboratories have documented a correlation between
      reduced gap-junction function and malignant transformation. In endometrial
      cancer, a characteristic finding is a reduction in the number of stromal cells
      surrounding the malignant epithelial cells. Thus, the focus of this study was to
      determine the effect of endometrial stromal cells on gap-junction function in
      normal and malignant endometrial epithelial cells. To perform these studies, we
      evaluated normal endometrial epithelial cells and human endometrial epithelial
      cells including FEEC (fetal endometrial epithelial cells immortalized with simian
      virus 40 large-T antigen), HEC-1A (endometrial carcinoma stage 1A), and RL-95-2
      (endometrial carcinoma grade II). Gap-junctional intercellular communication
      (GJIC) could not be demonstrated for any of the cell lines. Low levels of GJIC
      were observed for normal epithelial cells and higher levels were found between
      stromal cells. Increased levels of GJIC were observed between the epithelial
      cells when they were cocultured with stromal cells. The transformed epithelial
      cells showed no GJIC when cultured alone or when in coculture with stromal cells.
      The results suggest that endometrial stromal cells may help to regulate this
      differentiated function of endometrial epithelial cells and that malignant
      endometrial epithelial cells are not responsive to these regulatory signals. Mol.
      Carcinog. 28:70-75, 2000.

PMID- 10900461
TI  - Current awareness.
AB  - In order to keep subscribers up-to-date with the latest developments in their
      field, this current awareness service is provided by John Wiley & Sons and
      contains newly-published material on comparative and functional genomics. Each
      bibliography is divided into 16 sections. 1 Reviews & symposia; 2 General; 3
      Large-scale sequencing and mapping; 4 Genome evolution; 5 Comparative genomics; 6
      Gene families and regulons; 7 Pharmacogenomics; 8 Large-scale mutagenesis
      programmes; 9 Functional complementation; 10 Transcriptomics; 11 Proteomics; 12
      Protein structural genomics; 13 Metabolomics; 14 Genomic approaches to
      development; 15 Technological advances; 16 Bioinformatics. Within each section,
      articles are listed in alphabetical order with respect to author. If, in the
      preceding period, no publications are located relevant to any one of these
      headings, that section will be omitted

PMID- 10900465
TI  - Impaired nuclear accumulation and shortened phosphorylation of ERK after growth
      factor stimulation in cultured hepatocytes from rats exposed to 2
      acetylaminofluorene.
AB  - The hepatic carcinogen 2-acetylaminofluorene (AAF) exerts its effect as a tumor
      promoter by mitoinhibition of normal hepatocytes. Initiated cells proliferate
      selectively and develop into preneoplastic foci and subsequently into carcinomas.
      To study whether some of the mitoinhibitory effects of AAF could be attributed to
      an influence on intracellular signal transduction, growth factor signaling was
      studied in cultured hepatocytes from rats fed AAF for 7 d. Activation through the
      epidermal growth factor receptor (EGFR) was used to probe possible changes in
      downstream mitogenic signaling mechanisms. The proliferative response to
      epidermal growth factor (EGF), measured as proliferating cell nuclear antigen
      expression and thymidine incorporation, was almost completely inhibited in
      hepatocytes exposed to AAF. Neither EGFR protein levels nor EGF binding was
      notably altered in AAF-exposed hepatocytes as opposed to normal hepatocytes. The
      initial tyrosine phosphorylation of EGFR and downstream activation of Sos, Raf-1,
      and extracellular signal-regulated protein kinase (ERK) were similar in AAF
      treated and control hepatocytes. Even though ERK phosphorylation was unaffected,
      a remarkable (80%) reduction of ERK nuclear accumulation was observed in AAF
      exposed hepatocytes immediately after mitogen stimulation. EGFR tyrosine
      phosphorylation and downstream signaling lasted 6 h in control cells versus 2 h
      in AAF-exposed hepatocytes. We previously demonstrated that AAF inhibits the
      growth factor-dependent induction of cyclin D1 and arrests hepatocyte cell-cycle
      progression before the p21/CIP1-controlled DNA-damage check point. The present
      data indicate that the DNA-damaging carcinogen AAF induces growth inhibition by a
      distinct inhibition of ERK nuclear accumulation after mitogen stimulation.
      Inhibition of intracellular signal transduction may represent a novel mechanism
      of growth arrest. Mol. Carcinog. 28:84-96, 2000.

PMID- 10900464
TI  - Differential expression and localization of the mRNA binding proteins, AU-rich
      element mRNA binding protein (AUF1) and Hu antigen R (HuR), in neoplastic lung
      tissue.
AB  - Modulation of gene expression at the level of mRNA stability has emerged as an
      important regulatory paradigm. In this context, differential expression of
      numerous mRNAs in normal versus neoplastic tissues has been described. Altered
      expression of these genes, at least in part, has been demonstrated to be at the
      level of mRNA stability. Two ubiquitously expressed mRNA binding proteins have
      recently been implicated in the stabilization (Hu antigen R/HuR) or
      destabilization (AU-rich element mRNA binding protein [AUF1]/heterogeneous
      nuclear ribonucleoprotein D) of target mRNAs. Further, their functional activity
      appears to require cytoplasmic localization. In the present study, we demonstrate
      a strong correlation between increased cytoplasmic expression of both AUF1 and
      HuR with urethane-induced neoplasia and with butylated hydroxytoluene-induced
      compensatory hyperplasia in mouse lung tissue. In addition, when compared with
      slower growing cells, rapidly growing neoplastic lung epithelial cell lines
      expressed a consistently higher abundance of both AUF1 and HuR proteins.
      Moreover, in nontumorigenic cell lines, both AUF1 and HuR protein abundance
      decreased with confluence and growth arrest. In contrast, in spontaneous
      transformants, AUF1 and HuR abundance was unaffected by changes in cell density.
      We suggest that growth-regulated alterations in AUF1 and HuR abundance may have
      pleiotropic effects on the expression of a number of highly regulated mRNAs and
      that this significantly impacts the onset, maintenance, and progression of the
      neoplastic phenotype. Mol. Carcinog. 28:76-83, 2000.

PMID- 10900466
TI  - Effect of intragastric application of N-methylnitrosourea in p53 knockout mice.
AB  - Nullizygous p53 knockout (p53(-/-)) mice are highly susceptible to spontaneous
      tumorigenesis, in particular malignant lymphomas at an early age. Heterozygous
      p53 knockout (p53(+/-)) mice develop spontaneous tumors less frequently but may
      show increased susceptibility to chemical carcinogens. In this study, p53(-/-),
      p53(+/-), and p53 wild-type (p53(+/+)) mice were treated with N-methylnitrosourea
      (MNU) by gastric intubation (5 microg/g body weight) three times per week for 5
      wk, starting at 5-6 wk of age. The surviving mice were killed when they were 56
      57 wk old. All eight p53(-/-) mice treated with MNU developed malignant lymphomas
      with a shorter latent period (mean age = 16.4+/-0.5 wk) than their spontaneous
      tumors (61%, at age 23.3+/-1.4 wk). In p53(+/-) mice treated with MNU, malignant
      lymphomas developed at a higher frequency (eight of 27, 30%) than did spontaneous
      lymphomas (5%). Development of sarcomas in p53(-/-) and p53(+/-) mice was also
      significantly enhanced by treatment with MNU. All eight thymic lymphomas and
      three sarcomas in the p53(+/-) mice showed a loss of the remaining wild-type p53
      allele. These results indicate that intragastric MNU treatment significantly
      enhanced spontaneous development of malignant lymphomas and sarcomas in both p53(
      /-) and p53(+/-) mice. In the stomachs of 12 p53(+/-) mice, that were killed at
      the end of the experiment, two adenomas, one carcinoma in situ, and four
      adenocarcinomas were observed. In the stomachs of 31 p53(+/+) mice, eight
      adenomas and one carcinoma in situ were detected. The overall incidence of
      tumorous changes in the stomachs of p53(+/-) (seven of 12, 58%) and p53(+/+)
      (nine of 31, 29%) mice were not significantly different (P = 0.090). However,
      adenocarcinomas invading the submucosa were observed in p53(+/-) mice (four of
      12, 33%) but not in p53(+/+) mice (zero of 31; P = 0. 004), suggesting a slightly
      higher susceptibility to gastric carcinogenesis induced by MNU in p53(+/-) mice.
      Mol. Carcinog. 28:97-101, 2000.

PMID- 10900467
TI  - Cell-cycle arrest at G2/M and growth inhibition by apigenin in human colon
      carcinoma cell lines.
AB  - Apigenin, a common dietary flavonoid, has been shown to induce cell cycle arrest
      in both epidermal and fibroblast cells and inhibit skin tumorigenesis in murine
      models. The present study assessed the influence of apigenin on cell growth and
      the cell cycle in the human colon carcinoma cell lines SW480, HT-29, and Caco-2.
      Treatment of each cell line with apigenin (0-80 microM) resulted in a dose
      dependent reduction in both cell number and cellular protein content, compared
      with untreated control cultures. DNA flow cytometric analysis indicated that
      treatment with apigenin resulted in G2/M arrest in all three cell lines in a time
      and dose-dependent manner. Apigenin treatment (80 microM) for 48 h produced
      maximum G2/M arrest of 64%, 42%, and 26% in SW480 cells, HT-29 cells, and Caco-2
      cells, respectively, in comparison with control cells (15%). The proportion of S
      phase cells was not altered by apigenin treatment in each of the three cell
      lines. The G2/M arrest was reversible after 48 h of apigenin treatment in the
      most sensitive cell line SW480. The degree of G2/M arrest by apigenin was
      inversely correlated with the corresponding inhibition of cell growth
      measurements in all three cell lines (r = -0.626 to -0.917, P</=0. 005).
      Moreover, an immune complex kinase assay demonstrated an inhibition of p34(cdc2)
      kinase activity, a critical enzyme in G2/M transition, in each cell line after
      treatment with apigenin (50-80 microM). Western blot analyses indicated that both
      p34(cdc2) and cyclin B1 proteins were also decreased after apigenin treatment.
      These results indicate that apigenin inhibits colon carcinoma cell growth by
      inducing a reversible G2/M arrest and that this arrest is associated, at least in
      part, with inhibited activity of p34(cdc2) kinase and reduced accumulation of
      p34(cdc2) and cyclin B1 proteins. Differences in induction of G2/M arrest by
      apigenin in the three colon carcinoma cell lines suggest that dietary apigenin
      may be differentially effective against tumors with specific mutational spectra.
      Mol. Carcinog. 28:102-110, 2000.

PMID- 10900468
TI  - Chromium(VI) induces p53-dependent apoptosis in diploid human lung and mouse
      dermal fibroblasts.
AB  - Some forms of hexavalent chromium [Cr(VI)] are known to cause damage to
      respiratory-tract tissue and DNA and are thought to be human lung carcinogens. In
      general, Cr(VI) is mutagenic and carcinogenic at doses that also evoke some cell
      death, and we previously showed that the predominant mode of death is apoptosis.
      Because p53 has been shown to initiate apoptosis after genotoxic insults, the
      objective of these experiments was to determine whether p53 is activated in and
      necessary for apoptosis of normal diploid human lung fibroblasts (HLF cells)
      after chromium exposure. By using annexin(V) staining and fluorescent microscopy,
      we found that Cr(VI) caused up to 14% of HLF cells to undergo apoptosis within 24
      h after exposure. In addition, by using western blotting, we found that p53
      protein levels increased fourfold to sixfold after exposure to sodium chromate.
      Because the major function of p53 is as a transcription factor, it must be
      translocated from the cytoplasm to the nucleus after chromate exposure to be
      active. Immunofluorescence studies using an antibody against p53 showed that,
      after chromate exposure, p53 was located in the nucleus of the treated HLF cells.
      The necessity of p53 for chromium-induced apoptosis was examined in two ways. One
      approach used dermal fibroblasts from p53 wild-type, heterozygous, and null mice,
      and the other approach used HLF cells that were transiently transfected with the
      human papilloma virus E6 gene, which targets p53 for degradation and creates a
      functional p53-null cell. These studies showed that chromium-induced apoptosis
      was p53 dependent. Mol. Carcinog. 28:111-118, 2000.

PMID- 10900469
TI  - Identification of tumor-suppressor genes using human melanoma cell lines UACC903,
      UACC903(+6), and SRS3 by comparison of expression profiles.
AB  - The development and progression of cancer are believed to be due to multiple
      genetic alterations resulting in complex changes in expression of many genes. The
      parental malignant melanoma cell line UACC903 displays anchorage-independent
      growth, and the chromosome 6-suppressed subline UACC903(+6) displays anchorage
      dependent growth. The anchorage-independent revertant cell line SRS3 derived from
      UACC903(+6) by retroviral transduction resembles the phenotype of UACC903. In
      this study, we first compared the expression profiles of 3317 genes between these
      three cell lines in pairs by cDNA microarrays, resulting in identification of
      genes with known suppressor activities. We then demonstrated connexin 43 (Cx43)
      suppressing anchorage-independent growth of UACC903 on overexpression. Of 3317
      genes with informative expression detected by cDNA microarray, 321 (9.68%) showed
      expression changes between at least one pair of the three cell lines. Notably, 12
      genes displayed higher levels of expression in UACC903(+6) than in both UACC903
      and SRS3, providing candidates for further identification of melanoma-suppressor
      genes. Genes encoding Cx43 (suppressor activity), monocyte chemotactic protein 1
      (suppressor activity), and cysteine proteinase P32alpha (apoptotic activity) were
      all upregulated in UACC903(+6), in contrast to both UACC903 and SRS3.
      Transfection of Cx43, encoded on human chromosome 6q21-q23, a region frequently
      altered in malignant melanoma, resulted in its overexpression and the suppression
      of anchorage-independent growth of UACC903. Thus, our result proves the principle
      that the combination of the ability to alter cellular phenotype by successive
      genetic alterations and the ability to examine the global expression profiles
      facilitates the identification of tumor suppressor genes. Mol. Carcinog. 28:119
      127, 2000.

PMID- 10900470
TI  - Evolution of parasites and host-parasite relationships.

PMID- 10900471
TI  - New and re-emerging diseases: a dedication to Norman D. Levine.

PMID- 10900472
TI  - Hurrah for genome projects!

PMID- 10900473
TI  - Estimating the impact of amebiasis on health.

PMID- 10900475
TI  - Schistosomiasis vaccines: a response to a devils' advocate's view.

PMID- 10900476
TI  - Risk maps: transmission and burden of vector-borne diseases.

PMID- 10900478
TI  - Mosquito bites and wing beverages on the Web

PMID- 10900477
TI  - Blood-sucking: old or new? Unravelling the evolution of Trypanosoma cruzi.

PMID- 10900479
TI  - Virtual tools against trypanosomatids

PMID- 10900480
TI  - Lymphatic filariasis in the Philippines.
AB  - Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is endemic
      throughout most of the southern half of the Philippine archipelago. Economic and
      manpower shortages prior to 1996 made it difficult to acquire new prevalence data
      and vector control data concurrently from all provinces. Nevertheless, analysis
      of cumulative prevalence data on filariasis indicates the persistence of
      filariasis in each of the three major island groups - Luzon, Visayas and Mindanao
      - including 45 out of 77 provinces. Here, Michael Kron and colleagues summarize
      the prevalence data, and review host, parasite and vector characteristics
      relevant to the design and implementation of disease control initiatives in the
      Philippines planned for the year 2000.

PMID- 10900481
TI  - Helminth C-type lectins and host-parasite interactions.
AB  - C-type lectins (C-TLs) are a family of carbohydrate-binding proteins intimately
      involved in diverse processes including vertebrate immune cell signalling and
      trafficking, activation of innate immunity in both vertebrates and invertebrates,
      and venom-induced haemostasis. Helminth C-TLs sharing sequence and structural
      similarity with mammalian immune cell lectins have recently been identified from
      nematode parasites, suggesting clear roles for these proteins at the host
      parasite interface, notably in immune evasion. Here, Alex Loukas and Rick Maizels
      review the status of helminth lectin research and suggest ways in which parasitic
      worms might utilize C-TLs during their life history.

PMID- 10900482
TI  - Modelling a predictable disaster: the rise and spread of drug-resistantmalaria.
AB  - The evolution of drug-resistant malaria is one of the most important factors
      thwarting the development of effective malaria disease control. Several
      mathematical models have been developed to try and understand the dynamics of
      this process and how it can be slowed or even avoided. Much of the mathematics
      describing the evolution of drug resistance in malaria focuses on the derivation
      and mechanics of the calculations, which can make it inaccessible to
      experimentalists and field workers. In this article, Ian Hastings and Umberto
      D'Alessandro describe general model results without recourse to mathematical
      details, identify the factors that should be considered in the design of drug
      control programmes, and discuss the crucial parameters that remain unknown and
      need to be measured in the field or laboratory.

PMID- 10900484
TI  - Amplified restriction fragment length polymorphism in parasite genetics.
AB  - The amplified restriction fragment length polymorphism (AFLP) technique is a
      relatively new method for the analysis of polymorphism that has not yet been
      widely used in parasitology. In this article, Dan Masiga, Andy Tait and Mike
      Turner provide a brief introduction to AFLP and illustrate how it can be used in
      the investigation of marker inheritance in genetic crosses and in the analysis of
      polymorphism of field populations. They also briefly highlight the strengths and
      weaknesses of AFLP in comparison with other methods for detecting polymorphism
      and conclude that AFLP is a very useful addition to the range of techniques
      available.

PMID- 10900483
TI  - RNAi--prospects for a general technique for determining gene function.
AB  - Gene discovery programs centred around expressed sequence tag (EST) and genome
      sequencing projects have predictably led to an exponential surge in the number of
      parasite gene sequences deposited in public databases. To take advantage of this
      wealth of sequence information, it is essential to develop rapid methods for
      elucidating the biological function or mode of action of individual genes. Here,
      Patricia Kuwabara and Alan Coulson discuss the virtues of a powerful epigenetic
      gene disruption technique, RNA-mediated interference (RNAi), which was originally
      developed for the nematode Caenorhabditis elegans. It is anticipated that this
      technique will not only provide insights into gene function, but also help
      investigators to mine the genome for candidate drug intervention or vaccine
      development targets, some of which may not be readily apparent on the basis of
      sequence information alone.

PMID- 10900485
TI  - Identification of differentially regulated genes of Plasmodium by suppression
      subtractive hybridization.
AB  - Plasmodium, the causative agent of malaria, has many morphologically and
      functionally distinct developmental stages. In the mosquito host alone, there are
      five transitions during the development of a gametocyte into a sporozoite.
      Determining which genes are expressed at the different developmental stages is
      vital to our understanding of the parasite. There are a growing number of
      techniques designed to study gene expression, including microarray. Here,
      Johannes Dessens, Gabrielle Margos, Maria del Carmen Rodriguez and Robert Sinden
      describe a novel method: suppression subtractive hybridization (SSH) and its
      successful application in obtaining mosquito midgut stage-specific genes of
      Plasmodium.

PMID- 10900486
TI  - Schistosomiasis vaccines: what parasitology can do for immunology.

PMID- 10900488
TI  - Schistosomiasis vaccines: the Devils' Advocate's final plea

PMID- 10900487
TI  - The Schistosoma japonicum angle on vaccine research.

PMID- 10900489
TI  - Naturally acquired versus vaccine-induced immunity to malaria: a dual role for
      TGF-beta and IL-12?

PMID- 10900490
TI  - [Incidence of sensitization to profilin in a population allergic to pollen:
      responsibility of profilin in pollen polysensitizations in patients with a normal
      level of total IgE].
AB  - The study had the aim of establishing the incidence of sensitization to profilin
      (a panallergen found in pollens and foods of vegetal origin) in pollen-allergic
      patients. We evaluated the consequences of such sensitizations on the results of
      specific IgE, the positivity of skin tests and clinical signs. METHODS: 94
      consenting patients, allergic to pollens (trees and/or grasses and/or weeds)
      replied to a questionnaire and had skin tests to purified profilin and
      measurement of serum anti-profilin IgE. RESULTS: Two groups were defined: one
      group was sensitized to profilin (GSP), with positive skin test and anti profilin
      IgE of 31 patients, and a group non-sensitive to profilin (GNSP) (negative skin
      test and anti-profilin IgE) of 41 patients. Discordant results were found in 22
      patients. Taking in account the two groups, sensitization to profilin was 43%.
      The two groups were homogenous for age, sex, ethnics and clinical signs. Food
      allergy was more frequent but not statistically different (p = 0.09) in the group
      GSP (51.6%) than the GNSP (31.7%), in particular allergy to fruits of the
      Rosaceae family. Pollen polysensitization (to three species, trees, weeds and
      grasses) was more frequent in the GSP group (64.5%) than the GNSP (12.5).
      Polysensitization to pollens and foods was also more frequent in the sensitized
      group (65.5%) than in the non-sensitized group (12.5%). In a sub-group with
      normal levels of total IgE pollen polysensitization was more frequent in patients
      who were sensitive to profilin. On biological investigation, sensitization to
      profilin influenced the result of anti-latex IgE and also the IgE to many vegetal
      allergens. These results show the value of seeking a sensitization to profilin in
      patients with pollinoses.

PMID- 10900491
TI  - [Value of esophageal scintigraphy in exploration of a gastro-esophageal reflux in
      a respiratory patient].
AB  - Patients with respiratory pathologies in the forms of tracheitis, rhino
      sinusitis, and asthma sometimes have symptoms of gastro-oesophageal reflux, that
      should be taken into consideration in order to treat the co-factors associated
      with the etiopathology. However, these patients, because of their respiratory
      handicaps, are frequently unwilling to submit themselves to traumatic
      investigations. Oesophageal scintigraphy, because of its perfect tolerance and
      reliability, seems to be an examination that is adapted to the situation to
      resolve this dilemma.

PMID- 10900492
TI  - Educational program for children with peanut allergy.
AB  - The best approach to managing peanut allergy is to educate patient and family. We
      developed specific consultation for children with peanut allergy. We follow a
      structurized program in a pedagogical manner. The objectives of this program are
      to encourage appropriate understanding, recognition of the signs of allergy, and
      if it is necessary, to teach how to inject oneself with an epinephrine injection.
      The aim of these sessions is to improve knowledge on basic allergy, recognition
      of hidden foods, on reading labelling, on recognition of earliest signs and
      finally on use of epinephrine as a rescue treatment. Behaviour in restaurant and
      most of all at school is also precised. The interview began with the parents and
      children, followed by discussions and pedagogical games. Our subjects
      experiences, described below, suggest that these educational programs are
      beneficial. As the others chronic pathologies, patients with this program seem to
      have less allergic reactions, and are able to respond with the appropriate
      behaviour when symptoms appear. Three months later, we conduct the efficiency of
      the treaning.

PMID- 10900493
TI  - ["Diagnosis related groups" efficiency-oriented reimbursement system?].

PMID- 10900494
TI  - [Anesthesia in breast feeding. Which restrictions are justified?].
AB  - In the last years knowledge of the excretion of drugs into breast milk has
      increased significantly. But information concerning anesthetic and analgesic
      drugs seems to be dispersed and limited. This paper describes the pharmacokinetic
      principles of drug transfer to milk and offers a comprehensive survey for drugs
      used in the perianesthetic period. The necessity of anesthesia should never be a
      sufficient reason to quit breast-feeding. With the information given in this
      article the individual duration of breast-milk-free interval can be discussed.
      Thus it will be possible to anesthetize a breast-feeding mother with minimal
      risks for the child without giving up the advantages of mother milk. Through
      careful selection of appropriate drugs even elective operations don't need to be
      postponed and breastfeeding can be continued as soon as in the immediate
      postoperative period.

PMID- 10900495
TI  - [Recovery of balanced anesthesia with various inhalation anesthetics in
      comparison to intravenous anesthetics: a retrospective analysis of 20,060
      patients].
AB  - BACKGROUND: The aim of this investigation was to compare routine balanced
      anaesthesia with different inhalation agents to intravenous anaesthesia (IVA)
      using an Anaesthesia-Information-Management-System (AIMS) with regard to time of
      recovery from anaesthesia, the time of discharge from the postanaesthesia care
      unit (PACU) and postoperative nausea as well as postoperative therapy with
      analgesics. METHODS: In 1997 and 1998 all relevant data of each anaesthesia
      procedure have been recorded using the online documentation Software NarkoData.
      These data sets have been stored into a relational database during each
      anaesthesia procedure. For evaluation the information has been exported from the
      database to a statistics program via 'Structured Query Langvage' (SOL). Balanced
      anaesthesia has been performed using isoflurane, halothane, and sevoflurane,
      respectively, supplemented with or without nitrous Oxide (N2O). The intravenous
      based anaesthesia-groups included propofol-fentanyl or propofol-remifentanil.
      RESULTS: The fastest recovery was seen in patients of the isoflurane group (11.2
      +/- 7.7 minutes), and the longest time for extubation was observed in patients
      wich halothane anaesthesia (12.8 +/- 9.3 minutes); the overall mean difference
      was 1.7 minutes. The earliest patient admitted to the PACU had received
      sevoflurane (7.0 +/- 6.3 minutes) and propofol-remifentanil (7.0 +/- 7.4 minutes)
      whereas patients of the halothane group (9.5 +/- 7.5 minutes) took more. The
      shortest stay in PACU was seen in patients of the sevoflurane and isoflurane
      groups (105.13 +/- 35.7 and 108.4 +/- 60.5 minutes), whereas propofol
      remifentanil (126.2 +/- 89.1 minutes) and halothan (120.0 +/- 86.1 minutes)
      anaesthetised patients had the longest stay in PACU. No difference was noted in
      the incidence of postoperative nausea and vomiting nor in the amount of
      postoperatively given analgesics. CONCLUSION: Results achieved in routine
      correspond only in part to results from studies. In our investigation balanced
      anaesthesia with isoflurane and sevoflurane correspond with the shortest stay in
      PACU compared to balanced anaesthesia with halothane and IVAs with propofol
      fentanyl or propofol-remifentanil. One reason for this could be the
      intraoperatively administered opioide piritramide in IVAs. Furthermore we
      conclude that an AIMS may provide additional information about overall costs
      effectiveness. However this information depends largely on local factors, e.g.
      patient case mix, staffing, policy of discharge from the PACU etc.

PMID- 10900496
TI  - [Experience with G27 Whitacre needle in in-patient and out-patient settings-
      incidence of post dural puncture headaches and other side effects].
AB  - OBJECTIVE: The aim of the study was to evaluate the incidence of side-effects in
      patients bearing a high risk of post dural puncture headache (PDPH) when a spinal
      anaesthesia was performed. This included outpatients, patients for sectio
      caesarea and patients younger than 40 years who were mobilized as soon as the
      surgeon agreed. METHODS: Quality control without randomization. Spinal
      anaesthesia for sectio caesarea was applied with a G27 Whitacre needle with the
      patient in the right lateral decubitus position. Hyperbaric Bupivacain 2-2.2 ml
      (10-12 mg) was injected when spontaneous flow of spinal fluid occurred through
      the needle. The preparations for the surgery then started immediately with the
      patient in a left lateral position. Intravenous Ephedrin (10-20 mg) was given
      simultaneously. All the other spinal anaesthesias were performed in a similar
      manner with the patient lying on the side of the scheduled surgery. For
      outpatients Articain was used instead of Bupivacain. In those outpatients older
      than 60 years a 26 G Quincke needle was used for spinal anaesthesia. Interviews:
      All in-hospital patients were visited once or more during the first 48 hours and
      asked about side-effects e.g. PDPH. Outpatients older than 60 years were
      interviewed by a telephone call on the third day after surgery. The younger ones
      were asked to send back a questionnaire free of charge. RESULTS: None of the 206
      patients (mean age 30.7 years) who underwent caesarian sectio suffered from
      headache. Lower back pain was seldom [8] and moderate. They all had the bladder
      drained as a routine measure of the obstetrician. 547 of 600 in hospital patients
      were mobilized as soon as the block disappeared. 11 complained of headache.
      (1.8%) 2 females needed oral non-opioid analgesics, one 17-year-old woman an
      epidural blood patch (0.17%). 150 of the outpatients younger than 60 years sent
      back the questionnaire spontaneously. 75 had to be reminded by a telephone call.
      10 of these 225 had PDPH but only 2 females needed oral non-opioids for one day.
      One 34-year-old woman needed conservative treatment with oral fluid intake more
      than 3 liters a day, analgesics and bed rest. None of the outpatients older than
      60 years complained of headache. Two suffered from vomiting on the way home.
      Three males had disturbed bladder function, but did not need catheterism.
      CONCLUSIONS: The use of a thin pencil point needle (Whitacre G27) enables the
      application of a spinal anaesthesia to young people with a low risk of moderate
      PDPH. Pregnancy is not a contraindication. Early mobilisation does not increase
      the risk of PDPH even in young patients nor is this the case in outpatients. In
      outpatients older than 60 years a G26 Quinke needle, which is easier to handle
      and cheaper, is suitable for spinal anaesthesia without a risk of PDPH. Better
      post-operative vigilance may be a further benefit of the method. Young people
      especially appreciated the option to pursue their own video-endoscopic surgery.
      In a comparable group where an epidural was performed we found more side-effects.

PMID- 10900497
TI  - [Clonidine compared to midazolam for intravenous premedication for ambulatory
      procedures. A controlled double blind study in ASA 1 patients].
AB  - OBJECTIVE: Midazolam is frequently used for premedication in day-case surgical
      patients whereas clonidine is rarely administered for this indication. However,
      clonidine has several useful effects that make the drug an interesting
      alternative to conventional premedicants. Thus, in this randomised, double-blind,
      and controlled study the anxiolytic effect of midazolam was compared to that of
      clonidine. Furthermore, effects on postoperative complaints and minor
      complications, and readiness for discharge were investigated. METHODS: 100 ASA-1
      patients undergoing wisdom teeth extraction on a day-case basis were included
      into the analysis. A further 50 patients who received no premedication served as
      a control group. General anaesthesia was standardised (propofol-fentanyl
      isoflurane in N2O/O2). The anxiolytic effect of the premedication was assessed
      using the Erlanger anxiety- and tension scale (EAS). The test was applied before
      and after intravenous premedication with 1.5 micrograms/kg clonidine or 50
      micrograms/kg midazolam and repeated once postoperatively. During recovery the
      incidence and severity of pain, nausea and vomiting, and shivering were recorded.
      The readiness for discharge was assessed using standardised discharge criteria.
      The recording of data was completed by a telephone interview on the day after
      surgery. RESULTS: The demographic data of the groups did not differ. In the two
      treatment groups there was a time-dependent decrease of anxiety and tension.
      However, postoperatively there was no difference between the levels of anxiety
      and inner tension between the premedicated patients and the untreated control
      group. Furthermore there was no difference in the incidence and severity of any
      postoperative complications. Time until the patients were ready for discharge did
      not differ between the three groups. CONCLUSION: The effects of an intravenous
      premedication with 1.5 micrograms/kg clonidine or 50 micrograms/kg midazolam,
      respectively in young ASA-1 patients undergoing minor surgical procedures on a
      day-case basis are restricted to decrease of anxiety and inner tension before
      surgery. No beneficial effects were found during the postoperative period
      compared with untreated control patients.

PMID- 10900498
TI  - [Music therapy in chronic pain--theoretical basis--the Heidelberg model].

PMID- 10900499
TI  - [Accelerando--application of music therapy using improvization passages with
      controlled acceleration].

PMID- 10900500
TI  - [Music therapy as a treatment for chronic pain disorders: a case report].

PMID- 10900501
TI  - [Left ventricular aneurysm after myocardial contusion caused by blunt chest
      trauma].
AB  - A 30-year old male car-driver was polytraumatized after a frontal collision with
      another motor vehicle (left-sided rib fractures, right-sided pneumothorax,
      multiple lung contusions, anterior and posterior pelvic ring fracture, femoral
      shaft fracture, traumatic subarachnoid hemorrhage. After intubation and
      hemodynamic stabilization on the scene of accident, he was transported to our
      institution. Transesophageal echocardiography revealed a left-ventricular
      anteroseptal akinesia and patchy intramyocardial hyperdensities as indicator of
      myocardial contusion which was confirmed later by autopsy. In the further course,
      the patient developed an anteroseptal aneurysm with severe left ventricular
      dysfunction nad episodes of arrhythmias. Finally, septic shock complicated the
      case and the patient died 30 days of intensive care from therapy-refractory
      multiple organ system failure.

PMID- 10900502
TI  - [Induction of anti-meningitis immunity using the synthetic peptides. I. The
      immunoreactive synthetic fragments of porin A from Neisseria meningitidis].
AB  - Fourteen peptides corresponding to sequences of all the exposed and some of the
      transmembrane protein regions of porin A from the outer membrane of Neisseria
      meningitidis strain B:15:P1.7,16 were synthesize. Mice of various lines were
      immunized with the free peptides not conjugated with any protein carrier. It was
      shown that the majority of the peptides possess immunogenic properties. Two
      peptides were identified binding to antibodies present in the serum of mice after
      meningitis. Protective properties of a number of the synthesized peptides were
      studied, and three peptide sequences inducing mice protection from an
      experimental infection with N. meningitidis were identified.

PMID- 10900503
TI  - [Computer prediction of biological activity spectra for low-molecular peptides
      and peptidomimetics].
AB  - The wide variety of the biological effects of peptides and their high activity
      are the main reasons for the search for new basic drug structures among them. The
      most promising compounds can be selected using the PASS computer system
      (Prediction of Activity Spectra for Substances). This system was originally
      developed to predict the activities of low-molecular "drug-like" organic
      compounds. Its predictive capacity is described here by the example of 134
      peptides and peptidomimetics with nine known biological activities. Its average
      predictive power is shown to be approximately 97%. Such an accuracy demonstrates
      that computer prediction can be applied both to the evaluation of effects and
      mechanisms of action of endogenous and synthetic peptides and to the screening of
      new therapeutic agents among the most promising basic structures.

PMID- 10900504
TI  - [The endogenous differentiation factor of the HL-60 cells shows a nuclease
      activity].
AB  - A structural homology between the endogenous differentiation factor of the HL-60
      cell line of promyelocyte leukemia (HLDF) and several DNA/RNA-binding and DNA/RNA
      hydrolyzing proteins was revealed, and expression of the hldf gene in prokaryotic
      systems was studied. On the basis of these experiments, the amino acid sequence
      of an 8-membered fragment of HLDF with potential nuclease activity was
      identified. The synthetic octapeptide RRWHRLKE was shown to be capable of the
      cleavage of RNA, linear DNA from phage lambda, and all forms of plasmid DNA. We
      established that treatment of the HL-60 cell culture with this peptide (10(-6) M)
      results in an increase in the number of apoptotic cells and suggested that HLDF
      is involved in processes of apoptosis.

PMID- 10900505
TI  - [Proteolytic specificity of plasmin with respect to adhesive proteins].
AB  - We showed that plasmin specifically hydrolyzes proteins participating in cell
      adhesion (fibronectin, vitronectin, and laminin) and does not affect nonadhesive
      proteins, such as albumin, ovalbumin, and alkaline phosphatase. These and some
      earlier results allow us to speak of the specific antiadhesive activity of
      plasmin, which significantly extends the concepts regarding the functional
      importance of this protein and indicates that it directly participates in the
      regulation of cell adhesion, the remodeling of the extracellular matrix, and,
      therefore, in cell migration.

PMID- 10900506
TI  - [Regulation of hyaluronidase inhibition through its chemical modification].
AB  - The modification of hyaluronidase by aldehydodextran regulates inhibition of the
      enzyme by heparin. A 70-90% modification of the surface amino groups of
      hyaluronidase results in sharp conformational changes and a substantial decrease
      of its inhibition by heparin, whereas hyaluronidase derivatives with a
      modification degree of 96-100% are practically uninhibited.

PMID- 10900507
TI  - [The S,X-acetals in nucleoside chemistry. I. The synthesis of 2'- and 5'-O
      methylthiomethyl ribonucleosides].
AB  - Ribonucleoside 2'- and 5'-methylthiomethyl derivatives were synthesized from
      selectively protected nucleosides by the action of dimethyl sulfoxide-acetic
      anhydride-acetic acid mixture.

PMID- 10900508
TI  - [Synthesis of uracil and theophylline derivatives and study of their effect on
      glucose transport in rat hepatic cells].
AB  - A series of uracil and theophyllin derivatives were synthesized. 4-Amino-1,3
      dimethyl-5-nonanoylaminouracil displayed the most pronounced effect of the in
      vitro stimulation of the 2-deoxyglucose transport into hepatic rat cells.

PMID- 10900509
TI  - [The nature of stabilization of the tandem DNA duplex pTGGAGCTG (pCAGC + (Phn-NH
      (CH2)3-NH)pTCCA) based on the UV-, CD-, and two-dimensional NMR spectroscopy
      data].
AB  - Properties and three-dimensional structure of the tandem DNA duplex
      pTGGAGCTG.(pCAGC+(PhnL)pTCCA) in aqueous solution, where L is an amino linker and
      Phn is an N-(2-hydroxyethyl)phenazinium residue, were studied
      spectrophotometrically and by two-dimensional 1H NMR spectroscopy (COSY and
      NOESY). When a tandem complex involving a Phn residue-bearing oligonucleotide is
      formed, the dye aromatic system intercalates into the double helix at the nick
      site and takes part in two stacking interactions: a strong one (3.5-4 A) with the
      T5-A12 base pair of its own duplex moiety and a weak one (4-5 A) with the C4-G13
      pair of the adjoining duplex (mainly with the C4 base). This arrangement of the
      dye residue, providing a cross-interaction of the phenazinium moiety with the
      base pairs of the adjacent duplex structures, results in the stabilization of the
      whole tandem complex.

PMID- 10900510
TI  - [The structure of sulfated cauloside C].
AB  - The structure of the sulfated analogue of cauloside C, a biologically active
      triterpenoid glycoside, was elucidated to be 3-O-[beta-D-glucopyranosyl-(1-->2)
      alpha-L-arabinopyranosyl]-he deragenin 23,4',4",6"-tetrasulfate pentasodium salt
      by the comparison of its 13C NMR spectrum with that of cauloside C potassium
      salt.

PMID- 10900511
TI  - Cloning and characterization of the human ribosomal protein S21 gene [.
AB  - A full-size functional gene encoding the human ribosomal protein S21 was cloned
      and characterized. Its nucleotide sequence, exon-intron organization, and
      transcription initiation site were determined. The gene comprises 1417 bp and is
      composed of six exons and five introns. Like most known genes of mammalian
      ribosomal proteins, it lacks the canonical TATA- and CAAT sequences in the
      promoter region and harbors potential binding sites for transcription factors
      both upstream and downstream the transcription initiation site. The first intron
      of the rpS21 gene is located in the 5'-untranslated region. The transcription
      initiation site is at a 53-bp distance from the ATG codon, and the initiation
      cytidine is surrounded by polypyrimidine tracts. The 5'-flanking region contains
      two repeats belonging to the Alu-S and Alu-J families.

PMID- 10900512
TI  - [The lack of the CpNpG methylation at the 5'-terminal region of the human
      calcitonin gene in norm and in leukemia [].
AB  - The inner cytosine methylation was analyzed in the CCWGG sequences of the 5'
      terminal region of the human calcitonin gene from peripheral blood and bone
      marrow cells in various forms of leukemia. Since these sequences remain
      nonmethylated both in norm and in various leukemia forms, the CpG dinucleotide
      hypermethylation of the 5'-terminus of the human calcitonin gene, characteristic
      for the development of leukemias, does not spread over adjacent CpNpG sequences.

PMID- 10900513
TI  - Saving sight in sports.

PMID- 10900514
TI  - Vision standards for driving in Canada.

PMID- 10900515
TI  - Canadian Ophthalmological Society recommendations for driving standards and
      procedures in Canada. Canadian Ophthalmological Society Working Group on Driving
      Standards.

PMID- 10900516
TI  - Vision standards for driving in Canada and the United States. A review for the
      Canadian Ophthalmological Society.
AB  - We review the vision requirements for driving with the goal of revising current
      Canadian Ophthalmological Society (COS) recommendations for vision standards for
      driving. The report comprises two sections. In the first section we report the
      results of a survey of transportation authorities in Canada and the United States
      conducted on behalf of the COS to determine the current standards and medical
      review procedures. The results suggest that although the standards in Canada are
      more consistent than those in the United States, few of the standards in either
      country are evidence-based. In the second section we review the recent literature
      on visual function and driving. We conclude from this review that adequate
      contrast sensitivity is as important as, if not more important than, good visual
      acuity for driving and that there is little evidence to support a monocular
      standard for acuity, contrast sensitivity or visual field. Although there is
      evidence that the extent of a visual field defect is related to the ability to
      perform driving tasks, there is little evidence to suggest a relation between the
      location of the visual field defect and fitness to drive.

PMID- 10900517
TI  - Clinical variability among patients with incomplete X-linked congenital
      stationary night blindness and a founder mutation in CACNA1F.
AB  - BACKGROUND: Incomplete X-linked congenital stationary night blindness (CSNB) is a
      clinically variable condition that has been shown to be caused by mutations in
      the calcium-channel CACNA1F gene. We assessed the clinical variability in the
      expression of the incomplete CSNB phenotype in a subgroup of patients of
      Mennonite ancestry with the same founder mutation. METHODS: Sixty-six male
      patients from 15 families were identified with a common mutation in exon 27 of
      CACNA1F (L1056insC). Clinical variability in night blindness, reduced visual
      acuity, myopia, nystagmus and strabismus was examined. RESULTS: At least one of
      the major features of CSNB (night blindness, myopia and nystagmus) was absent in
      72% of the patients. All the examined features varied widely, both between and
      within families. INTERPRETATION: Although the patients shared a common CACNA1F
      mutation, there was considerable variability in the clinical expression of the
      incomplete CSNB phenotype. These findings suggest the presence of other genetic
      factors modifying the phenotype of this disorder.

PMID- 10900518
TI  - Effect of latanoprost as adjunctive therapy.
AB  - BACKGROUND: Latanoprost may be a useful adjunct in some patients receiving
      maximum tolerated medical therapy. We report our clinical experience with
      latanoprost when added to one or two other glaucoma medications. METHODS: Review
      of the charts of 53 patients with open-angle glaucoma whose intraocular pressure
      (IOP) was uncontrolled with one or two glaucoma medications and who had
      latanoprost added as a second or third drug. Patients whose IOP decreased by 3 mm
      Hg or more were considered to be responders. RESULTS: The shortest length of
      follow-up was 2.3 months (median 5.8 months). Latanoprost was given as a second
      medication to 35 patients, of whom 22 (63%) responded, with a mean IOP reduction
      of 6.1 mm Hg (standard deviation [SD] 2.73 mm Hg) (28.7% [SD 12.10%]). Of the 18
      patients to whom latanoprost was given as a third medication, 10 (56%) responded,
      with a mean IOP reduction of 6.3 mm Hg (SD 3.86 mm Hg) (24.5% [SD 10.12%]).
      INTERPRETATION: Latanoprost provides additional IOP reduction in some patients
      with open-angle glaucoma when added to one or two other glaucoma medications.

PMID- 10900519
TI  - Severe ocular injury from orthodontic headgear.

PMID- 10900521
TI  - Transcultural psychiatry: goals and challenges.

PMID- 10900520
TI  - Epithelial ingrowth following penetrating keratoplasty: a clinical, ultrasound
      biomicroscopic and histopathological correlation.

PMID- 10900522
TI  - Transcultural psychiatry: personal experiences and Canadian perspectives.
AB  - In the mid-1950s, a unique section of transcultural psychiatric studies was
      established within the McGill Department of Psychiatry. These personal
      recollections describe the backgrounds, methods, and motivations of those most
      involved and suggest why such a specialized study should have emerged in Canada
      and at McGill. Some of the major controversies and developments in the field are
      explored, focusing on the question of culture-bound syndromes and their
      occasional biological underpinnings. The relevance of transcultural psychiatry to
      psychiatric practice is discussed.

PMID- 10900523
TI  - The future of cultural psychiatry: an international perspective.
AB  - Cultural psychiatry has evolved along 3 lines: 1) cross-cultural comparative
      studies of psychiatric disorders and traditional healing; 2) efforts to respond
      to the mental health needs of culturally diverse populations that include
      indigenous peoples, immigrants, and refugees; and 3) the ethnographic study of
      psychiatry itself as the product of a specific cultural history. These studies
      make it clear that culture is fundamental both to the causes and course of
      psychopathology and also to the effectiveness of systems of healing. The
      provision of mental health services in multicultural societies has followed
      different models that reflect their specific histories of migration and
      ideologies of citizenship. Globalization has influenced psychiatry through
      socioeconomic effects on the prevalence and course of mental disorders, changing
      notions of ethnocultural identity, and the production of psychiatric knowledge. A
      cultural perspective can help clinicians and researchers become aware of the
      hidden assumptions and limitations of current psychiatric theory and practice and
      can identify new approaches appropriate for treating the increasingly diverse
      populations seen in psychiatric services around the world.

PMID- 10900524
TI  - [Organization of health care in geriatric psychiatry: a consensus statement].
AB  - This consensus statement, originally published in English by the World Health
      Organization (WHO), has been produced in collaboration with the Section of
      Geriatric Psychiatry of the World Psychiatric Association (WPA). During a meeting
      in Lausanne, Switzerland, from November 14 to 16, 1997, led by Dr Nori Graham,
      the final declaration was prepared by an interdisciplinary group of
      representatives from the principle international associations concerned.
      Professor Cornelius Katona and Dr Nori Graham were Co-Rapporteurs. This statement
      follows an initial consensus document published by the WHO and the WPA defining
      geriatric psychiatry (1).

PMID- 10900525
TI  - Different perspectives of the therapeutic alliance and therapist technique in 2
      forms of dynamically oriented psychotherapy.
AB  - OBJECTIVE: This study addresses several issues concerning patients' and
      therapists' perceptions of key therapy process variables. This includes examining
      whether patients and therapists differ in their perceptions of the therapeutic
      alliance and therapist technique, what the relation is between perceptions of the
      alliance and technique, and whether these perceptions are predictive of treatment
      outcome. METHOD: Patient and therapist perceptions of the therapy process were
      provided in a comparative trial of 2 forms of short-term individual dynamic
      psychotherapy. Patients (n = 144) were randomly assigned to each condition.
      Treatment outcome was assessed using a large, comprehensive battery of reliable
      measures. RESULTS: The findings revealed several differences in the patients' and
      therapists' ratings of the alliance and technique in the 2 forms of therapy.
      Patient ratings of the alliance and technique were predictive of treatment
      outcome. CONCLUSION: The findings contribute to understanding the extent to which
      therapy participants share views of therapy processes and highlight the
      importance of the therapist's attending to the patient's perception of therapy.

PMID- 10900526
TI  - Physical illness as an outcome of chronic anxiety disorders.
AB  - BACKGROUND: The literature indicates increased rates of some medical conditions
      in patients with anxiety disorders. We used the Saskatchewan Health databases to
      examine the development of nonpsychiatric medical diseases in patients with
      anxiety disorders. This study has a large population base, and the Saskatchewan
      health plan does not limit the provision of services to this population. METHOD:
      We observed the annual incidence of specified medical conditions in patients with
      anxiety disorders and in control subjects over a 10-year period. Subjects in both
      groups had not been treated for the specified medical conditions before the start
      of the observation period. RESULTS: The anxiety cohort had a significantly higher
      relative risk of developing medical diseases compared with the control group. The
      highest relative risk, indicated by the hazard ratio, was for cerebrovascular
      disease (hazard ratio 2, 95% CI 1.09-3.65). Hazard ratios were significant for
      cerebrovascular disease and atherosclerosis as well as for ischemic heart,
      gastrointestinal, hypertensive, and respiratory diseases. CONCLUSIONS: This study
      provides additional evidence for an association between anxiety disorder and the
      later development of medical morbidity.

PMID- 10900527
TI  - Childhood depressive symptoms predict psychiatric problems in young adults.
AB  - OBJECTIVE: To evaluate the predictive value of childhood depressive symptoms for
      psychiatric symptoms, adaptive functioning, and self-performance in young adults.
      METHOD: The study sample consisted of 111 young adults born during 1975-1976 in
      the Helsinki region. The young adults were assessed in childhood (10 to 11 years
      of age) using the Children's Depression Inventory (CDI) and at the age of 20 to
      21 years using Achenbach's Young Adult Self Report (YASR), the Beck Depression
      Inventory (BDI), and the Wallston Self-Performance Survey. RESULTS: Self-reported
      depressive symptoms in childhood predicted psychiatric symptoms (especially
      aggression), poor adaptive functioning, and low self-esteem in young adulthood.
      CONCLUSIONS: Depressive symptoms in children should be addressed to prevent later
      psychiatric problems. The CDI may be a measure of nonspecific psychopathology
      rather than of pure depression--thus, it may be a good screening tool for child
      populations.

PMID- 10900528
TI  - Comparison of shoplifting behaviours in patients with eating disorders,
      psychiatric control subjects, and undergraduate control subjects.
AB  - Shoplifting behaviours were examined in an eating disorder group (EDG, n = 48), a
      psychiatric control group (PCG, n = 46), and an undergraduate control group (UCG,
      n = 82). They were examined in relation to self-esteem, depression, and eating
      disorder symptomatology. The 3 groups did not differ in overall history of
      shoplifting, but EDG women were more likely to have shoplifted in the past 6
      months (current shoplifting) and to have shoplifted often than were women from
      the PCG or UCG. Across all 3 groups, current shoplifting was associated with low
      self-esteem, elevated depression, and purging behaviours at the time of the
      assessment. The implications of these findings with regard to the relationship
      between shoplifting and eating disorder symptomatology will be addressed.

PMID- 10900529
TI  - Strategies for managing depression refractory to selective serotonin reuptake
      inhibitor treatment: a survey of clinicians.
AB  - OBJECTIVE: To examine treatment practices in cases where selective serotonin
      reuptake inhibitors (SSRIs) are ineffective. METHODS: We surveyed 801 clinicians
      (including 630 psychiatrists) attending the Massachusetts General Hospital's
      annual psychopharmacology review course. Clinicians were presented with a
      vignette about a patient with depression who had responded partially to an SSRI
      and were asked to choose among various strategies available to manage this
      patient. RESULTS: Of those surveyed, 466 clinicians had been in practice a mean
      of 16.6 years (SD 10.7). Not all clinicians chose to answer every question. Among
      455 respondents, 84% (n = 382) chose to increase the dose of the SSRI, 10% (n =
      47) chose augmentation or combination, and 7% (n = 31) opted for switching
      agents. When asked to switch to another agent, 448 responded, of whom 52% (n =
      235) chose a newer antidepressant, 34% (n = 152) chose another SSRI, 10% (n = 44)
      chose a tricyclic antidepressant (TCA), 2% (n = 8) chose a serotonin
      norepinephrine reuptake inhibitor (SNRI), 1% (n = 5) chose a monoamine oxidase
      inhibitor (MAOI), and 1% (n = 4) chose an undefined "other" agent. Among 445
      respondents, bupropion was the most widely chosen augmenting agent (30%, n =
      134), followed by lithium (22%, n = 98). West coast and Canadian clinicians
      preferred to switch to another SSRI rather than to a newer antidepressant.
      Canadian clinicians preferred lithium to bupropion as their first-choice
      augmenting agent, as did clinicians from academic settings. Clinicians from
      community, individual practice, or group settings favoured bupropion. More
      experienced clinicians preferred bupropion as a first-choice augmenter, whereas
      less experienced ones showed a slight preference for lithium. Canadian clinicians
      were more likely to use MAOIs as second-line agents. CONCLUSIONS: Clinicians in
      this sample often followed strategies different from those recommended in the
      literature. Bupropion may have an important role in augmentating treatment with
      SSRIs.

PMID- 10900530
TI  - Pathological laughter and obsessive-compulsive disorder in patients with
      affective illnesses.

PMID- 10900531
TI  - Citalopram plus reboxetine in treatment-resistant depression.

PMID- 10900532
TI  - Age at onset of bipolar II disorder with Axis I comorbidity.

PMID- 10900533
TI  - Seizures associated with sertraline.

PMID- 10900534
TI  - Nephrolithiasis on topiramate therapy.

PMID- 10900535
TI  - Olanzapine and weight gain.

PMID- 10900536
TI  - Ictal mania: a case report.

PMID- 10900537
TI  - Monoolein: a review of the pharmaceutical applications.

PMID- 10900538
TI  - Bioequivalence study of paracetamol tablets: in vitro-in vivo correlation.
AB  - The bioequivalence of three chemically equivalent paracetamol generic Mexican
      products (500 mg tablets) was evaluated in 12 healthy volunteers using the
      American innovator product (Tylenol, McNeil, Fort Washington, PA), as the
      reference. Single oral doses of each product were administered at 1-week
      intervals using a 4 x 4 Latin square design balanced for the first residual
      effect. The total amount of paracetamol excreted in urine in 24 hr was taken as a
      measure of bioavailability. In addition, moment analysis was used to estimate in
      vitro mean dissolution time (MDT) from dissolution profiles obtained following
      the USP 23 dissolution test specified for paracetamol tablets and to estimate in
      vivo mean residence time (MRT) from urinary excretion data. Significant
      differences in the dissolution performance and in the cumulative amount of
      paracetamol excreted in urine up to 24 hr were observed when the data were
      analyzed by analysis of variance (ANOVA) (p < .05). Classical and Westlake 90%
      confidence limits, as well as the two-sided t test proposed by Schuirmann, and
      the Anderson-Hauck power analysis supported the final conclusion that only one of
      the three generic paracetamol products studied can be considered equivalent to
      the reference product Tylenol. A linear correlation between in vitro MDT and in
      vivo MRT was found.

PMID- 10900539
TI  - Sustained-release butorphanol microparticles.
AB  - Various butorphanol-loaded microparticles have been prepared with a biodegradable
      copolymer P(FAD-SA) of erucic acid dimer (FAD) and sebacic acid (SA) and a
      copolymer P(CPP-SA) of carboxyphenoxypropane (CPP) and SA using a melt
      compounding and milling method. Drug release was measured in vitro following
      incubation of drug-loaded microparticles in water for injection at 37 degrees C.
      It was found that butorphanol was released in a sustained manner, yielding a
      cumulative drug release of about 100% over a period of 48 hr. Also, drug release
      was affected by drug loading and the size of the microparticles; however, it was
      not significantly influenced by the copolymer composition. Scanning electron
      microscopic (SEM) results showed that most of the particles were irregular in
      shape with uneven surfaces. The molecular weights of the copolymers were not
      changed after this fabrication process. In addition, 20% butorphanol-encapsulated
      microspheres were prepared with copolymer P(FAD-SA) by spray-drying. The SEM
      micrograph shows that the particle sizes of the microspheres ranged from 2 to 10
      microns, and the external surfaces appear smooth. Moreover, rapid drug release
      was observed for these microspheres, with more than 92% of the encapsulated drug
      released within the first 2 hr.

PMID- 10900540
TI  - Polymers with pH-dependent solubility: possibility of use in the formulation of
      gastroresistant and controlled-release matrix tablets.
AB  - Polymers usually utilized for gastroresistant film coating of tablets or pellets
      such as cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT),
      hydroxypropylmethylcellulose phthalate (HPMCP), and Eudragit L and S were used in
      the preparation of drug/polymer matrix tablets. These tablets were prepared
      either by direct compression of both powders or by the formulation of
      microspheres that were then compressed. The microspheres were characterized by
      scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and
      X-ray diffractometry analyses. Dissolution studies were finally carried out to
      verify if the tablets possessed gastroresistant or controlled-release
      characteristics. Except for Eudragit L, the polymers can be used under certain
      conditions in the formulation of modified-release tablets.

PMID- 10900541
TI  - Preparation of polymeric microcapsules: formulation studies.
AB  - Air-filled microcapsules were prepared by freeze-drying different oil-in-water
      emulsions containing biodegradable polyester as the wall-forming material. The
      aim of this work was to find an acceptable formulation with respect to the
      microcapsule suspension and the stability of the emulsion during the production
      process. The influence of various formulation parameters (concentrations of
      mannitol, polymer, and surfactant; pH; oil-in-water phase ratio) was investigated
      in a factorial design. The results were treated by ordinary least-square (OLS)
      regression and partial least-square regression (PLSR). In a previous work, air
      filled microcapsules were successfully made using human serum albumin as the
      surfactant in the emulsion (1). In the present work, a new block copolymer based
      on poly(ethylene glycol) (PEG) was implemented as the surfactant to replace human
      serum albumin. It was found that the new block copolymer is a suitable
      replacement for human serum albumin. The concentration of the polymer in water
      and the concentration of the surfactant in the oil phase and the interaction
      between these variables had a significant influence on the stability of the
      emulsion at 60 degrees C. A surfactant concentration of approximately 2% (w/v) in
      water was necessary when the concentration of the wall-forming polymer was below
      5% (w/v) in (-)-camphene. The concentration of the polymer in the oil phase
      influenced the yield, measured as the volume concentration of particles in
      suspension per milligram of polymer added and as acoustic effect per milligram of
      polymer. Low levels of polymer concentration in (-)-camphene (< 5% w/v) gave the
      highest yield. Excess polymer in the oil phase did not form microcapsules, but
      precipitated in the suspension or was included in the wall of the microcapsules.
      Addition of mannitol protected the microcapsules from being destroyed during
      freeze-drying and resulted in freeze-dried products with few cracks, little
      shrinkage, and higher suspension yield.

PMID- 10900542
TI  - Studies of floating dosage forms of furosemide: in vitro and in vivo evaluations
      of bilayer tablet formulations.
AB  - For the purpose of enhancement the bioavailability of furosemide (FR), a floating
      dosage form with controlled release of FR was designed in this study. Because of
      the lower solubility of active material in the gastric medium, it was first
      enhanced by preparing an inclusion complex of FR with beta-cyclodextrin (beta-CD)
      in a 1:1 proportion using the kneading method. Following the design of dosage
      form, bilayer floating tablets were prepared. After dissolution rate studies were
      performed using the continuous flow-through cell method, the formulation that
      provided delivery of active material near the target profile was given to six
      healthy male volunteer subjects, and in vivo tests were performed. It was
      determined by radiographs that floating tablets prepared by adding BaSO4 stayed
      in the stomach for 6 hr. Further, values of the area under the plasma
      concentration-time curve (AUC) obtained with the floating dosage form were about
      1.8 times those of the conventional FR tablet in blood analyses; maximum and
      minimum plasma concentrations were also found to be between the desired limits.
      In urine analyses, the peak diuretic effect seen in classical preparations was
      decreased and prolonged in floating dosage forms. Also, a considerably
      significant correlation was detected between in vivo results and in vitro data of
      the dissolution rate, and it was concluded that the modified continuous flow
      through cell method is usable for in vitro dissolution rate tests of floating
      dosage forms.

PMID- 10900543
TI  - A stability-indicating HPLC method to determine cyproterone acetate in tablet
      formulations.
AB  - A simple and accurate liquid chromatographic method was developed to estimate
      cyproterone acetate (CA) in pharmaceuticals. The drug was chromatographed on a
      reversed-phase C18 column. Eluents were monitored at a wavelength of 254 nm
      utilizing a mixture (60:40) of acetonitrile and water. Solution concentrations
      were measured on a weight basis to avoid the use of an internal standard. The
      method was statistically validated for linearity, accuracy, precision, and
      selectivity. Due to its simplicity and accuracy, we believe that the method can
      be used for routine quality control analysis. No specific sample preparation is
      required except for the use of a column guard and a suitable prefilter attached
      to the syringe.

PMID- 10900544
TI  - Optimization of the formulation and characterization of the physicochemical
      properties of the novel platelet-activating factor receptor antagonist E5880.
AB  - The injectable formulation of E5880, a novel platelet-activating factor (PAF)
      receptor antagonist, was determined from the study of pH stability, the selection
      of excipient, and the relationship between moisture and stability. The
      physicochemical properties of E5880 in the optimized formulation (0.6 mg/ml of
      E5880, 0.1% [4.8 mM] citric acid, 10% lactose, pH 2.8) were characterized. The
      critical micelle concentration of E5880 in the buffer was 0.1 mg/ml, and the
      structure was of spherical micelles. The micellar size was 5.6 nm and did not
      change before and after lyophilization and storage. The number of the molecules
      per micelle was 40. The micropolarity around the hydrocarbon region of the
      micelle was similar to that of butanol.

PMID- 10900545
TI  - Simultaneous determination of thiabendazole and mebendazole in tablets by high
      performance liquid chromatography.
AB  - Reversed-phase high performance liquid chromatography using an RP 18 column (4 x
      125 mm), tetrahydrofuran-acetonitrile-0.5% formic acid (5:25:70, v/v/v) as mobile
      phase and UV detection at 254 nm enabled the simultaneous determination of
      thiabendazole (TZ) and mebendazole (MZ) in tablets. The method showed linearity
      over 4.0 to 40.0 micrograms TZ/ml and 6.0 to 60.0 micrograms MZ/ml. The
      correlation coefficient r was .9999 for both TZ and MZ. The coefficient of
      variation (CV) was 0.59-0.80% for TZ and 0.49-0.67% for MZ. The average recovery
      was 100.54-101.17% for TZ and 100.35-101.13% for MZ. The excipients of the
      tablets did not interfere in the proposed method. The developed method is
      precise, accurate, and selective for the determination of both benzimidazoles
      analyzed.

PMID- 10900546
TI  - Evaluation and comparison of a moist granulation technique to conventional
      methods.
AB  - In the moist granulation technique (MGT), a minimum amount of liquid is used to
      activate a binder in a planetary mixer. Then, any excess moisture is absorbed by
      the addition of a moisture-absorbing substance. In the experiments described
      below, acetaminophen (APAP) was the model drug; polyvinylpyrrolidone (PVP) and
      microcrystalline cellulose (MCC) served as the binder and moisture-absorbing
      material, respectively. Water was used as the granulating fluid. Comparison of
      the MGT with direct compression (DC) and wet granulation (WG) methods was
      accomplished by sieve analysis (particle size) and density measurements. Moist
      granulation yielded an increase in particle size compared to direct compression;
      these results are comparable to those from the traditional wet granulation after
      drying and screening. Based only on the particle size, moist granulation appears
      comparable to conventional wet granulation for this formula. The moist
      granulation technique appears to have potential for the development of controlled
      release formulations.

PMID- 10900547
TI  - Improved dissolution rate of poorly soluble drug by incorporation of buffers.
AB  - This study focused on comparing dissolution rates of indomethacin after co
      compressing with three different buffers (calcium carbonate, sodium carbonate,
      and sodium citrate) at pH 2 and 7. Factors affecting the dissolution rate were
      also examined, such as type and particle size of buffer and weight-to-weight
      ratio of drug to buffer. It was found that, at pH 7, the release rates of
      indomethacin with sodium carbonate (< 74 microns, all proportions) and sodium
      citrate (< 74 microns, 75% loading) at a 20-min test time were about 10-fold and
      6-fold greater, respectively, than that of indomethacin alone. When the drug and
      buffer were compressed into tablets using a tableting machine, the release rates
      of indomethacin for the control, sodium carbonate incorporated (25% and 75%
      buffer loading), and sodium citrate incorporated (75% buffer loading) at a 15-min
      test time were 50%, 90%, 66%, and 67%, respectively.

PMID- 10900548
TI  - Particle size determination of a three-component suspension using a laser
      scattering particle size distribution analyzer.
AB  - In this study, a rapid and accurate particle size determination method using a
      light-scattering particle size analyzer was developed to measure the particle
      size and size distribution of a suspension containing three solid components:
      clotrimazole, triamcinolone, and sarafloxacin, which have different refractive
      indices. To ensure that data represent the size distribution of the primary
      particles of the suspension, the optimal sonication prior to and during
      measurement was determined. It was found that the results obtained using the
      average relative refractive index (RRI) of the three components agreed with the
      results obtained using three individual RRIs. In addition, the results from two
      analysts demonstrated good reproducibility of this method. The size distribution
      data of the suspension were also compared to those of the bulk drugs. The results
      showed that the median particle size of this three-component suspension is
      relatively close to that of clotrimazole, which accounts for 80% of solid
      particles in the suspension. Furthermore, the results obtained using the light
      scattering technique were comparable to those obtained using a polarized light
      microscope equipped with an image analyzer, indicating acceptable accuracy of
      this technique.

PMID- 10900550
TI  - The effect of lipid A analog E5531 on membrane properties of
      dipalmitoylphosphatidylcholine.
AB  - The effect of the lipid A analog E5531 on the phospholipid membrane was
      determined and compared with that of the lipid A from Escherichia coli (EC).
      E5531 decreased the phase transition temperature of
      dipalmitoylphosphatidylcholine (DPPC) membrane and increased the fluidity and
      permeability. On the other hand, EC increased the phase transition temperature
      and decreased the membrane fluidity and permeability. These results suggest that
      the reason for the difference of biological effects of E5531 and lipid A from EC
      would be caused by the differences from the effect on the cell membranes.

PMID- 10900549
TI  - Formulation and evaluation of Methocel K15M bioadhesive matrix tablets.
AB  - Methocel K15M is a bioadhesive polymer. Its adhesion and bioadhesion
      characteristics were evaluated by shear stress measurement and detachment force
      measurement methods, respectively. The effect of pH on adhesion was studied, and
      it was found that the maximum adhesion was between pH 5 and pH 6. Adhesion
      strength at different parts of the sheep intestine was studied; in the duodenal
      portion of the intestine, the adhesion was maximum. Chlorpheniramine maleate and
      diclofenac sodium drugs are formulated with Methocel K15M as matrix tablets. In
      vitro release studies revealed that some of the formulations showed initial first
      order behavior followed by zero-order release behavior.

PMID- 10900552
TI  - Vitamin A equivalence of beta-carotene in a woman as determined by a stable
      isotope reference method.
AB  - BACKGROUND: Quantitative information on conversion of beta-carotene to vitamin A
      in humans is limited. AIM OF THE STUDY: Our laboratory has developed a stable
      isotope method for studying the conversion of beta-carotene (beta-C) to vitamin
      A. METHODS: Two dosage levels (a pharmacological dose, 126.0 mg beta-C-d8, and a
      physiological dose, 6.0 mg beta-C-d8) were used 2.5 y apart in an adult female
      volunteer to study dose effects on the conversion of beta-C to vitamin A. Blood
      samples were collected over 21 d. beta-C and retinol were extracted from serum
      and isolated by high performance liquid chromatography. The retinol fraction was
      derivatized to a trimethylsilyl ether which was analyzed by gas
      chromatograph/mass spectrometry with electron capture negative chemical
      ionization. RESULTS: The retinol-d4 response in the circulation peaked at 24
      hours after the beta-C-d8 dose, with a higher percent enrichment after the
      pharmacological dose than after the physiological dose. By using retinyl acetate
      d8 as the vitamin A reference, the retinol-d4 formed from 6 mg of beta-C-d8 (11.2
      mumol) was calculated to be equivalent to 1.6 mg of retinol (i.e., 3.8 mg of beta
      C was equivalent to 1 mg of retinol). However, the retinol-d4 formed from 126 mg
      of beta-C-d8 (235 mumol) was equivalent to 2.3 mg of retinol (i.e., 55 mg beta-C
      was equivalent to 1 mg retinol). CONCLUSION: These results provide evidence that
      it is feasible to use stable isotope reference method to study retinol
      equivalence of beta-C and that there may be a dose-dependence on bioconversion of
      beta-carotene to retinol.

PMID- 10900551
TI  - Magnesium balance studies in premature and term infants.
AB  - BACKGROUND: The knowledge of magnesium requirements of premature infants is still
      very limited, although it is essential for the optimal composition of suitable
      formulas. AIM OF THE STUDY: The study concept was 1) to assess physiological
      magnesium balance data of healthy term infants and longitudinal results from
      formula-fed premature infants and 2) to deduce conclusions on the magnesium
      content of the formulas. METHODS: Premature infants (n = 14, birth weight < or =
      1500 g, gestational age < or = 32 weeks) were studied in conventional balance
      trials with 1) a semi-elemental diet (A), 2) preterm infant formula (B), and 3)
      infant formula (C). In addition, healthy term formula-fed (n = 11, D) and breast
      fed (n = 14, E) infants were investigated. Analysis was performed by flame atomic
      absorption spectroscopy. RESULTS: The median magnesium intake ranged between 4.84
      mg/kg x d-1 (breast-fed infants) and 16.33 mg/kg x d-1 (premature infants). The
      term breast-fed infants retained nearly as much magnesium as term formula-fed
      infants (3.37 vs. 3.97 mg/kg x d-1), due to a low percental fecal and urinary
      excretion. A higher magnesium retention was observed in the premature group: A:
      7.97 mg/kg x d-1, B: 5.3 mg/kg x d-1, 3.) C: 5.54 mg/kg x d-1. CONCLUSION: In
      view of the high percental magnesium retention in formula-fed premature infants,
      excessive supply should be avoided. The long-term effects of lower intakes have
      to be monitored.

PMID- 10900553
TI  - Inhibitory effect of wheat fibre extract on calcium absorption in Caco-2 cells:
      evidence for a role of associated phytate rather than fibre per se.
AB  - BACKGROUND: In spite of the strong evidence for the beneficial health effects of
      dietary fibres, one of the potential nutritional disadvantages of high fibre
      diets is the adverse effect on the bioavailability of micronutrients, especially
      minerals and trace elements. With regard to Ca, there is considerable evidence
      that phytate, which is associated with fibre in many foods, such as cereals and
      soya products, inhibits Ca absorption. However, there is some doubt as to whether
      fibres per se have an influence on Ca absorption. AIM OF THE STUDY: Therefore,
      the purpose of this study was to investigate the effect on Ca absorption of two
      cereal-based fibre extracts (wheat bran and barley hull). In addition, in order
      to distinguish between the effect of the fibre components per se and the
      associated phytate content in these fibre extracts, we investigated the effect of
      dephytinised wheat and barley fibre extracts and the effect of phytate, as sodium
      phytate at levels present in the fibre extracts, on Ca absorption. Ca absorption
      was assessed in Caco-2 cells, as a model for studying Ca absorption in humans.
      METHODS: The effect of wheat and barley fibre extracts, dephytinised wheat and
      barley fibre extracts, cellulose, and of sodium phytate on transepithelial 45Ca
      transport and 45Ca uptake was studied in differentiated Caco-2 cells grown on
      permeable filter supports. Wheat and barley fibre extracts were dephytinised with
      wheat phytase. RESULTS: Wheat fibre extract had a 3.2-fold higher phytate content
      (48.0 mmol/kg) than barley fibre extract (15.1 mmol/kg). Enzymatic
      dephytinisation of both fibre extracts reduced the phytate content to
      undetectable levels. The rate of transepithelial 45Ca transport across Caco-2
      cell monolayers and the uptake of 45Ca into Caco-2 cells were unaffected by
      cellulose or barley fibre extract. On the other hand, inclusion of wheat fibre
      extract in the Ca transport buffer (50 g fibre/l) significantly reduced the rate
      of 45Ca transport (by 17 and 19% respectively) and the uptake of 45Ca (by 24 and
      25% respectively) relative to a fibre-free buffer and a control fibre (cellulose)
      transport buffer. Increasing the phytate concentration of the transport buffer
      from 0 to 2 mM (a level close to that in the wheat fibre containing buffer)
      significantly reduced the rate of 45Ca transport (by 16%) and 45Ca uptake (by
      26%). Dephytinisation of the wheat fibre extract removed its inhibitory effects
      on 45Ca transport and e.g. 45Ca uptake. CONCLUSION: The results from the present
      study in Caco-2 cells suggest that it is the phytate in wheat fibre extract which
      is the major inhibitory factor of Ca absorption and that wheat fibre per se has
      little if any inhibitory effect on Ca absorption. In addition, the results of
      this study support the usefulness of Caco-2 cells for investigating the effects
      of dietary factors on the cellular uptake and transepithelial intestinal
      transport of Ca.

PMID- 10900554
TI  - Diet restriction in mice causes differential tissue responses in total reducing
      power and antioxidant compounds.
AB  - BACKGROUND: Diet restriction (DR) has been shown to extend the life spans of
      various laboratory animals, the mechanism may involve a decrease in oxidative
      stress. When determining if the total tissue defense has been altered, it is
      important to observe the overall direct antioxidant capacity, which consists of
      low molecular weight antioxidants (LMWA) and enzymes. AIM: To determine DR
      induced changes in total reducing power and overall direct antioxidant capacity
      of various mouse tissues. METHODS: Young female Sabra mice were fed a 60% food
      restricted diet for 40 days (DR group). Organs of the DR group and of ad libitum
      (AL) fed controls were then dissected and examined. A cyclic voltammetry method
      was used to quantify the total reducing power, which correlates with the overall
      LMWA activity. Specific LMWA were identified by HPLC-ECD. Superoxide dismutase
      activity and H2O2 degrading ability were measured in order to include the
      enzymatic antioxidant component. RESULTS: Short-term DR caused alterations in the
      total reducing power of various mouse tissues, indicating changes in the total
      scavenging ability of these tissues. Overall direct antioxidant capacity of
      heart, kidney and muscle was enhanced; liver and small intestine deteriorated;
      brain did not differ between DR and AL groups; lung and spleen exhibited a mixed
      response. CONCLUSIONS: We have shown for the first time that DR causes changes in
      the total reducing power of different mouse tissues, thus, affecting the overall
      direct antioxidant capacity. These findings support the suggestion that there may
      be a biological regulation of the antioxidant system.

PMID- 10900555
TI  - The fatty acid composition of human colostrum.
AB  - We reviewed 15 studies reporting on the fatty acid composition of colostrum
      lipids from 16 geographic regions: 11 European studies and one study each from
      Central America, the Caribbean, Australia and Asia. The contents of essential
      fatty acids, saturates and polyunsaturates were similar in the southern European
      countries Spain, Slovenia and France. Colostrum of St. Lucian women was high in
      saturates and low in oleic acid, reflecting a high-carbohydrate, low-fat diet.
      Abundant fish intake was reflected in high contents of docosahexaenoic acid and
      total n-3 long-chain polyunsaturated fatty acids in St. Lucia. Two French studies
      published with an interval of two years showed a very similar colostrum fatty
      acid composition, whereas two German studies obtained with an interval of 14
      years showed higher docosahexaenoic acid and arachidonic acid contents in the
      later study, with an unchanged n-6/n-3 long-chain polyunsaturated fatty acid
      ratio. Studies from Spain reported a decline of alpha-linolenic acid in colostrum
      over a time period of 13 years. Colostrum of Australian women contained the
      lowest polyunsaturated/saturated and n-6/n-3 long-chain polyunsaturated fatty
      acids ratios (0.28 and 1.58) and the lowest contents of linoleic and alpha
      linolenic acids (7.8 and 0.4 wt.%). In contrast, the contents of docosahexaenoic
      acid, eicosapentaenoic acid and total n-3 long-chain polyunsaturated fatty acids
      (0.6, 0.4 and 1.4 wt.%) were higher in Australian than in European samples. Fatty
      acid composition of human colostrum appears to be markedly influenced by
      geographic differences in maternal dietary composition.

PMID- 10900556
TI  - Role of glutamine on the de novo purine nucleotide synthesis in Caco-2 cells.
AB  - BACKGROUND: The body's nucleotide pool derives from three potential sources: de
      novo synthesis, salvage of preformed-nucleosides/bases or the diet. The relative
      contributions of these pathways of assimilation are poorly understood in vivo.
      Dietary nucleotides have been suggested to have beneficial effects an the
      development and repair of the gastrointestinal tract. Tissues with a rapid
      turnover, such as the gut and the immune system cells, may utilise preformed
      nucleotides (coming from the diet), in situations in which there is a high demand
      of nucleotides for nucleic acid synthesis. Therefore, nucleotides could be
      considered as conditionally essential nutrients. AIM OF THE WORK AND METHODS:
      Development of a method to measure synthesis de novo of RNA-purine nucleotides in
      Caco-2 cells, relying an the incorporation of 14C-glycine into the purine ring of
      the nucleotide. To establish the fractional synthesis rate of RNA purine
      nucleotides in Caco-2 cells, grown in culture medium containing different
      concentrations of glutamine, in the presence or absence of added nucleotides. To
      investigate the degree to which tissue ribonucleosides are derived from the
      culture medium or from de novo synthesis in the presence of different
      concentrations of glutamine, using undifferentiated Caco-2 cells, stressed or not
      by the addition of IL-1 beta to the medium. RESULTS AND CONCLUSIONS: The presence
      of high levels of glutamine in the culture medium is essential for cell
      proliferation (estimated by measurement of the fractional synthesis rate of
      purine nucleotides) and the presence of nucleotides cannot replace the glutamine
      dependence of Caco-2 cell proliferation. The incorporation of exogenous purine
      nucleotides into RNA of Caco-2 cells is rather limited, and it becomes important
      when cells are stressed by glutamine deprivation. Stress by addition of
      interleukin-1 beta resulted in the maintenance or the increase in de novo
      synthesised RNA-purine nucleotides, even in the presence of exogenous
      nucleotides. However, the addition of interleukin-1 beta to the culture medium
      led to an enhanced salvage of preformed pyrimidine nucleotides for nucleic acid
      synthesis when glutamine was present in the medium at a concentration of 0.5
      mmol/L.

PMID- 10900558
TI  - The association between depressive symptoms and cigarette smoking in an urban
      primary care sample.
AB  - OBJECTIVE: To examine the relationship between cigarette smoking and depressive
      symptoms in an urban primary care sample. METHODS: Eligible participants were 526
      patients aged eighteen to sixty-four presenting in the waiting rooms of two
      university affiliated internal medicine clinics. Participants were asked to
      complete a brief interview which ascertained current depressive symptoms using
      the Center for Epidemiologic Studies Depression Scale (CES-D), demographic
      information, and smoking status using a modified version of the Fagerstrom Test
      for Nicotine Dependence (FTND). RESULTS: Smoking status differed significantly by
      age, gender, education, and employment status. Mean level of depressive severity
      also differed by smoking status. Current smokers with nicotine dependence
      symptoms had significantly higher CES-D scores than those who had never smoked,
      ex-smokers, and non-dependent smokers. Logistic regression analyses indicated
      that gender, employment status, age, and smoking status were significantly
      associated with CES-D scores > or = 16. Exploratory analyses suggested that among
      smokers with a symptom of nicotine dependence, significantly more women than men
      had clinically significant levels of depressive symptoms. CONCLUSIONS: The
      association between smoking behavior and depressive symptoms in the present study
      is consistent with that reported in population-based and psychiatric samples.
      Symptoms of nicotine dependence were significantly associated with clinical
      levels of depressive symptoms. Primary care physicians may wish to inquire about
      depressive symptoms among smokers, because these symptoms may interfere with
      patients' efforts to quit.

PMID- 10900557
TI  - Diagnosis, treatment, comorbidity, and resource utilization of depressed patients
      in a general medical practice.
AB  - OBJECTIVE: The objective of the study was to determine the effect of depression
      on the utilization of health care resources, after adjusting for age and
      comorbidity from data obtained on routine clinical practice. METHOD: The study is
      an observational cohort of 15,186 patients followed over a one-year period
      beginning December 1993. Comprehensive demographic, clinical, and utilization
      data were available from the computerized medical information system generated
      database of a general internal medicine practice in an urban academic medical
      center. RESULTS: Four point seven percent of patients carried a provider-coded
      diagnosis of depression. With regards to utilization of health care resources,
      even after controlling for age and comorbidity, depressed patients had more
      primary care visits (5.3 vs. 2.9 visits, p < .001), higher rates of referral to
      specialists (1.1 vs. 0.5, p < .002), and radiologic tests (0.9 vs. 0.4 tests, p <
      .001). They had higher total outpatient charges ($1,324 vs. $701, p < .001) and
      total charges ($2,808 vs. $1,891, p < .001). Depressed patients also had longer
      length of stay when hospitalized (14.1 vs. 9.5 days, p < .002). CONCLUSIONS:
      Patients diagnosed as depressed had significantly higher resource utilization of
      all types, even after controlling for the higher burden of comorbid medical
      illness associated with depression.

PMID- 10900559
TI  - Serum cholesterol in patients with obsessive compulsive disorder during treatment
      with behavior therapy and SSRI or placebo.
AB  - OBJECTIVE: Patients with panic disorder are reported to have elevated cholesterol
      levels. There is also some evidence that cholesterol elevation is not so much a
      specific condition in panic disorder but is generally associated with anxiety. So
      far, there is little data on cholesterol levels in patients with obsessive
      compulsive disorders (OCD) which is also classified as anxiety disorder. METHOD:
      Thirty-three patients with OCD participated in the study. Serum cholesterol was
      measured as pretreatment and at the end of a ten-week treatment-period. All
      patients received behavior therapy and, in a double-blind fashion, fluvoxamine or
      placebo. Severity of OCD was assessed by the Yale-Brown Obsessive Compulsive
      Scale (Y-BOCS). RESULTS: Pretreatment cholesterol values of OCD patients were
      compared with cholesterol levels of thirty panic disorder patients and thirty
      normal controls. OCD patients had elevated cholesterol levels comparable with
      those of panic disorder patients. Cholesterol levels decreased significantly from
      pre- to posttreatment. OCD patients with high cholesterol levels (> or = 240
      mg/dl, n = 7) could make best use of the treatment whereas patients with
      desirable cholesterol levels (< 200 mg/dl, n = 11) did not change their
      cholesterol during treatment. CONCLUSIONS: Our data support the assumption that
      not only panic disorder but also other anxiety disorders, e.g., obsessive
      compulsive disorders, may be associated with serum cholesterol elevations.
      Effective treatment (behavior therapy and/or treatment with a selective serotonin
      reuptake inhibitor [SSRI]) seems to decrease cholesterol levels, especially in
      patients with pathological cholesterol elevations.

PMID- 10900560
TI  - Measuring psychological adjustment to HIV infection.
AB  - AIMS: A modified version of the Mental Adjustment to Cancer Scale (The Mental
      Adjustment to HIV Scale--MAHIVS) was used to evaluate patterns of psychological
      adjustment in response to HIV infection. METHODS: A sample of 164 HIV positive
      homosexual/bisexual men were recruited across three Australian centers (79
      asymptomatic (CDC II/III) and 85 symptomatic HIV infection (CDC IV)). Factor
      analysis of the MAHIVS was conducted and the predictive validity of the MAHIVS
      was investigated using the General Health Questionnaire, while The Diagnostic
      Interview Schedule was used to assess current and lifetime psychiatric disorder.
      Other measures of adjustment/coping were used to investigate the construct
      validity of the MAHIVS (neuroticism, locus of control, defense style). RESULTS:
      Factor analysis of the MAHIVS detected four factors: Hopelessness, Fighting
      Spirit/Self Efficacy, Personal Control, and Minimization. Hopelessness and
      Fighting Spirit factors exhibited acceptable levels of internal consistency and
      validity, with significant correlations detected with psychological symptoms and
      significant association with other measures of psychological adjustment and
      personality. Fighting Spirit emerged as a potential indicator of psychological
      resilience, whereas Hopelessness was significantly associated with psychological
      symptoms and current major depression (but not past depression). CONCLUSIONS: The
      findings indicate the validity of the MAHIVS and support the presence of common
      themes in the psychological adaptation to life-threatening illness that can be
      detected across disease categories and groups.

PMID- 10900561
TI  - Client empowerment in psychiatry and the professional abuse of clients: where do
      we stand?
AB  - OBJECTIVE: There is a considerable imbalance of power in psychiatry that sits in
      favor of professionals. The abuse and discrimination of the mentally ill are not
      just restricted to the mental health system but may also exist in the primary
      care sector. This article aims to evaluate the effects of power imbalance on
      discrimination and abuse of people with mental illness by professionals. METHODS:
      A literature search was carried out on MEDLINE using the key words consumerism,
      client empowerment, abuse, and mental illness. Publications of two leading
      British consumer organizations: MIND and the Sainsbury Centre for Mental Health
      were hand searched. Relevant cross-references from the papers reviewed were
      consulted. Studies with information on the reasons for power imbalance and
      prevalence of discrimination and abuse of clients were critically reviewed.
      Explanations are offered as to why abuse and discrimination of clients by
      professionals may still occur despite the onset of the client empowerment
      movement. RESULTS AND DISCUSSION: The available evidence suggests that reasons
      for abuse of mental health clients fall under two broad categories: 1) direction
      from the imbalance of power and 2) those pertinent to the nature of physical or
      sexual abuse. Different grades of client empowerment and ways of strengthening it
      are described. CONCLUSIONS: There appears to be a link between power imbalance
      and abuse of clients with mental illness by professionals in all health care
      sectors. Client empowerment may help rectify the power imbalance. Prospective
      studies are required to establish whether client empowerment can reduce
      discrimination and abuse of clients and whether abuse is a consequence of power
      imbalance. Recommendations for future studies are made.

PMID- 10900562
TI  - Difference in symptom profile between generalized anxiety disorder and anxiety
      secondary to hyperthyroidism.
AB  - OBJECTIVE: The differential diagnosis between subclinical hyperthyroidism and
      Generalized Anxiety Disorder (GAD) is often a difficult problem to solve without
      laboratory examination. The aim of this pilot study was to assess whether there
      are differences in the symptom profile between these two disorders. METHODS:
      Fifty patients took part in the study: Twenty-five were hyperthyroid patients,
      and twenty-five were GAD patients. The diagnosis was based on the TSH values and
      the DSM-IV criteria, respectively. The Hamilton Anxiety Scale (HAS) and the list
      of fifty-one symptoms produced by the detailed expansion of HAS items were used
      to quantify the anxiety symptomatology. The differences in the frequencies
      between the two diagnostic groups were calculated at each categorical response
      for every item of both scales. Forward Stepwise Discriminant Function Analysis
      was performed twice using HAS items and the fifty-one-list items. RESULTS: The
      symptoms of anxiety in subclinical hyperthyroidism were not identical to those of
      GAD. Four Hyperthyroid/Anxiety Indices (HAI I-IV) were developed. These indices
      reach optimum classification of patients (3 of them reach 100% sensitivity and
      specificity). CONCLUSION: The results of the current study suggest that it is
      possible to differentiate between GAD and subclinical cases of hyperthyroidism by
      the careful study of clinical symptomatology. This may be of particular help in
      isolated areas without laboratory support, but replication of the indices in
      other samples is indicated.

PMID- 10900563
TI  - Delusional parasitosis: a clinical profile.
AB  - OBJECTIVE: Delusional parasitosis is a form of monohypochondriacal psychosis, a
      condition sometimes encountered in psychiatric or primary care practice. The
      outcome of this condition is not well known. METHOD: In the present study, a
      series of fifty-two consecutive cases of delusional parasitosis is reported.
      RESULTS: A majority of cases (92%) had insidious onset. The duration of symptoms
      in all but two cases was six months or more. Twenty-six cases presented with a
      delusion of infestation by insects over the body and twenty-three cases with a
      delusion of insects crawling over the scalp. Three cases had associated diabetes
      mellitus, five cases had leprosy, five cases dementia, four cases had depression,
      and three cases presented with trichotillomania. Pimozide was used in forty-six
      cases, amitriptyline and fluoxetine in three cases each. Twenty-eight cases (54%)
      showed complete remission while receiving pharmacotherapy, eighteen cases showed
      partial improvement, and six cases did not respond to treatment. CONCLUSION:
      Further studies are warranted to study the treatment and outcome of this
      important psychiatric disorder.

PMID- 10900564
TI  - Pseudoseizures associated with doll phobia.
AB  - This report outlines a unique case of pseudoseizures associated with doll phobia
      in a young adult. Early recognition and treatment directed at the aetiological
      factors led to the effective treatment of the pseudoseizures and doll phobia.

PMID- 10900565
TI  - Incremental validity of the Rorschach Prognostic Rating Scale over the MMPI Ego
      Strength Scale and IQ.
AB  - A recent meta-analysis found that the Rorschach Prognostic Rating Scale (RPRS)
      had a strong ability to predict subsequent outcome (r = .44, N = 783; Meyer &
      Handler, 1997, this issue). However, that review did not directly address
      questions of incremental validity. This article focuses on the ability of the
      RPRS to predict outcome after taking into account other sources of data. Across
      studies that examined both the RPRS and the MMPI Ego Strength scale, the RPRS had
      a strong ability to predict outcome (r = .40, N = 187), whereas the MMPI scale
      did not (r = .02, N = 280). Nine studies examined the RPRS along with an
      intelligence test and allowed direct numerical estimates of incremental validity
      to be calculated. Across studies, the RPRS demonstrated strong incremental
      validity after controlling for intelligence (incremental r = .36, N = 358). It is
      clear that the Rorschach can make unique contributions to understanding
      clinically relevant processes in ways that self-reports or measured intelligence
      cannot. Contemporary Rorschach scales should continue to be evaluated for their
      distinctive and incremental contribution to clinical practice.

PMID- 10900566
TI  - Sentence completion tests: a review of the literature and results of a survey of
      members of the Society for Personality Assessment.
AB  - Test usage surveys consistently find that sentence completion tests (SCTs) are
      among the most popular personality assessment instruments used by practitioners.
      What is not noted is which SCTs practitioners are using, why these tests are so
      popular, and whether practitioners are using formal scoring. We surveyed a random
      selection of 100 members of the Society for Personality Assessment. With a 60%
      return rate on a single mailing, we found that most psychologists who use
      incomplete sentence tests use the Rotter (1951) Incomplete Sentences Blank with
      children (18%), adolescents (32%), and adults (47%). Most practitioners said they
      do not read stems aloud and record answers themselves, and even fewer said they
      use formal scoring. The most common reasons for using an SCT are (a) to use it as
      part of an assessment battery (41 endorsements), (b) to determine personality
      structure (18 endorsements), and (c) to elicit quotable quotes (17 endorsements).
      Implications for practitioners and training suggestions for academicians who
      prepare future psychologists are noted.

PMID- 10900567
TI  - Predictors of suggestibility and false-memory production in young adult women.
AB  - Recent controversy over memories retrieved in therapy has highlighted the
      importance of increasing our understanding of individual differences in
      suggestibility and false-memory production. The purpose of this laboratory study
      was to assess the ability of several clinically relevant variables (acquiescence,
      self-esteem, and negative affect) to predict the tendency to yield to suggestive
      questioning, to alter responses in the face of interpersonal criticism, or to
      produce false memories (in this study, false recall of implied words). Results
      indicated that acquiescence significantly predicted suggestibility, as did
      competence self-esteem scores, but global self-esteem and negative affect scores
      did not. False-memory production (i.e., false recall of implied words) was
      associated with higher levels of both acquiescence and negative affect, but the
      tendency to alter responses after criticism was not significantly predicted by
      any variable.

PMID- 10900568
TI  - Interpretation of a full-information item-level factor analysis of the MMPI-2:
      normative sampling and nonpathognomonic descriptors.
AB  - An exploratory item-level full-information factor analysis was performed on the
      normative sample for the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer,
      1989). This method of factor analysis, developed by Schilling and Bock (Bock &
      Schilling, 1997) and based on item response theory, works directly with the
      response patterns and avoids the artifacts associated with phi coefficients and
      tetrachoric coefficients. Promax rotation of the factor solution organizes the
      clinical scale items into 10 factors that we labeled Distrust, Self-Doubt,
      Fitness, Serenity, Rebelliousness, Instrumentality, Irritability, Artistry,
      Sociability, and Self-Reliance. A comparison was made to the results of Johnson,
      Butcher, Null, and Johnson (1984), who performed a principal-component analysis
      on an item set of 550 items from the previous version of the MMPI (Hathaway &
      McKinley, 1943). Along with version changes and sampling differences, the
      essential differences between Johnson et al.'s results and ours may be attributed
      to differences between the Schilling and Bock method, which uses all information
      in the item responses, and the principal-component analysis, which uses the
      partial information contained in pairwise correlation coefficients. This study
      included 518 of the complete 567 items of the MMPI-2, versus Johnson et al.'s
      retention of 309 of the initially included 550 items of the previous MMPI. The
      full-information analysis retained all 518 initially included items and more
      evenly distributed the items over the 10 resulting factors, all sharply defined
      by their highest loading items and easy to interpret. Sampling effects and factor
      label considerations are discussed, along with recommendations for research that
      would validate the clinical utility of the implied scales for describing normal
      personality profiles. The full-information procedure provides for Bayes
      estimation of scores on these scales.

PMID- 10900569
TI  - MMPI-2 Personality Psychopathology Five (PSY-5) and prediction of treatment
      outcome for patients with chronic back pain.
AB  - This study investigated the utility of the MMPI-2-based Personality
      Psychopathology Five (PSY-5) scales (Harkness, McNulty, & Ben-Porath, 1995) in
      the outcome prediction of behaviorally oriented chronic-pain treatment. The PSY-5
      is a dimensional descriptive system for personality and its disorders. The sample
      consisted of 120 consecutive chronic-back-pain patients who followed a 4-week
      multimodal treatment program aimed at achieving a normal pattern of functioning,
      including return to regular work. The psychometric properties of the PSY-5 scales
      (Aggressiveness, Psychoticism, Constraint, Negative Emotionality/Neuroticism, and
      Positive Emotionality/Extraversion) were highly similar to the data reported by
      Harkness et al. (1995) and also corresponded to the characteristics of chronic
      pain patients. The results of the hierarchical regression analyses provided
      support for the utility of the PSY-5 Positive Emotionality/Extraversion scale for
      the prediction of emotionally oriented outcome. We conclude that the PSY-5 model
      of personality psychopathology provides a solid basis for the more systematic
      study of the complex relation between personality characteristics and
      multidimensional treatment.

PMID- 10900570
TI  - Psychological needs associated with MMPI-2 scales in a nonclinical sample.
AB  - The psychological needs derived from the Adjective Check List (ACL; Gough &
      Heilbrun, 1983b) that are associated with MMPI-2 scales were studied among 198
      nonclinical participants. Both the Depression (D) and Psychasthenia (Pt) scales
      were negatively correlated with needs for achievement and dominance and
      positively correlated with needs for abasement and succorance (dependence). The
      Schizophrenia (Sc) scale was negatively associated with need for affiliation and
      positively associated with need for abasement. The Social Introversion (Si) scale
      was associated negatively with needs for achievement, dominance, affiliation,
      heterosexuality, exhibition, and autonomy and associated positively with needs
      for succorance, abasement, and deference, reflecting good construct validity for
      Scale Si. MMPI-2 Masculinity-Femininity (Mf) did not correlate with the ACL
      Masculinity and Femininity scales, suggesting poor concurrent validity for Mf.

PMID- 10900571
TI  - Characteristics factor structures of the Japanese version of the State-Trait
      Anxiety Inventory: coexistence of positive-negative and state-trait factor
      structures.
AB  - Previous factor studies of the State-Trait Anxiety Inventory (STAI; Spielberger,
      Gorsuch, & Lushene, 1970) have reported certain typical factors that are state
      trait (S-T) 2-factor solutions and positively-negatively (P-N) worded item 2
      factor solutions in addition to 4-factor solutions (positively and negatively
      worded state factors, positively and negatively worded trait factors). We
      explored the possibility that these factor structures are included in a factor
      space. Responses to the Japanese version of the STAI in a sample of 848 male
      workers were factor analyzed. The first-order factors obtained from principal
      component analysis were almost equal to the previous 4 factors, except for a
      minor factor, and their second-order factors were the P-N factors. However, the S
      T factors were also obtained from the same first-order factors by the oblique
      Procrustes rotation. Moreover, coexistence of these two 2-factor structures was
      determined in the same factor space by the orthogonal Procrustes rotation.

PMID- 10900572
TI  - Inventory of Interpersonal Problems Personality Disorder scales: operating
      characteristics and confirmatory factor analysis in nonclinical samples.
AB  - Research involving clinical samples has demonstrated the utility of a 28-item
      personality disorder (PD) screening measure (Inventory of Interpersonal Problems-
      Personality Disorder scale [IIP-PD]) culled from the IIP in the prediction of the
      presence or absence of a PD (Pilkonis, Kim, Proietti, & Barkham, 1996). This
      article extends these diagnostic efficiency findings to nonclinical samples and
      presents additional data regarding the factor structure of the 28 IIP-PD items.
      Diagnostic efficiency statistics for the IIP-PD scale, calculated using both
      interview and self-report methods, support the utility of the IIP-PD scale as a
      screening tool for the presence or absence of a PD. High specificity estimates
      indicate that individuals who do not exceed Diagnostic and Statistical Manual of
      Mental Disorders (4th ed.; American Psychiatric Association, 1994) symptom
      thresholds rarely exceed the IIP-PD cutoff. Furthermore, a high negative
      predictive power (NPP) estimate derived using an interview-based diagnostic
      standard suggests that the IIP-PD scale accurately screens out individuals who do
      not have a PD. Finally, cross-validated confirmatory factor-analytic results
      involving items composing the 5 IIP PD subscales identified in previous research
      (Kim, Pilkonis, & Barkham, 1997) suggest that a measurement model with a single
      second-order factor (general PD) and 5 first-order factors (one representing each
      PD subscale) provided the best fit to the observed data compared to 2 other
      competing models.

PMID- 10900573
TI  - Effects of response sets on NEO-PI-R scores and their relations to external
      criteria.
AB  - Validity scales indicate the extent to which the results of a self-report
      inventory are a valid indicator of the test taker's psychological functioning.
      Validity scales generally are designed to detect the common response sets of
      positive impression management (underreporting, or faking good), negative
      impression management (overreporting, or faking bad), and random responding. The
      revised NEO Personality Inventory (NEO-PI-R; Costa & McCrae, 1992b) is a popular
      personality assessment tool based on the 5-factor model of personality and is
      used in a variety of settings. The NEO-PI-R does not include objective validity
      scales to screen for positive or negative impression management. The purpose of
      this study was to examine the utility of recently proposed validity scales for
      detecting these response sets on the NEO-PI-R (Schinka, Kinder, & Kremer, 1997)
      and to examine the effects of positive and negative impression management on
      correlations between the NEO-PI-R and external criteria (the Interpersonal
      Adjective Scale-Revised-B5 [Wiggins & Trapnell, 1997] and the NEO-PI-R Form R).
      The validity scales discriminated with reasonable accuracy between standard
      responding and the 2 response sets. Additionally, most correlations between the
      NEO-PI-R and external criteria were significantly lower when participants were
      dissimulating than when responding to standard instructions. It appears that
      response sets of positive and negative impression management may pose a
      significant threat to the external validity of the NEO-PI-R and that validity
      scales for their detection might be a useful addition to the inventory.

PMID- 10900575
TI  - Correction to Meyer and Handler (1997).

PMID- 10900574
TI  - The Eating Attitudes Test: validation with DSM-IV eating disorder criteria.
AB  - The Eating Attitudes Test (EAT; Garner & Garfinkel, 1979) is one of the most
      widely used self-report eating disorder instruments. Originally developed to
      diagnose anorexia nervosa, it is often used in nonclinical samples where it has a
      high false-positive rate, which is likely due to changes in diagnostic criteria.
      Because the EAT has not been validated with Diagnostic and Statistical Manual of
      Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994)
      criteria, we examined its criterion validity for discriminating between
      nonclinical women with and without an undifferentiated DSM-IV eating disorder
      diagnosis. We also examined differences in mean EAT scores among eating
      disordered, symptomatic, and asymptomatic participants. Results show that the EAT
      has an accuracy rate of at least 90% when used to differentially diagnose those
      with and without eating disorders and that mean EAT scores differed among eating
      disordered, symptomatic, and asymptomatic participants.

PMID- 10900576
TI  - Obesity in adolescent girls. Emerging role of reproductive health professionals.
AB  - Reproductive health professionals who care for adolescent girls are often
      confronted with the issue of obesity either through specialty reproductive health
      concerns or as the primary providers of gynecologic or obstetric health care for
      young women. There are some significant health concerns that result from obesity
      in girls; therefore, this review summarizes the epidemiology, evaluation and
      management of adolescent obesity, focusing on issues pertinent to young women's
      health care.

PMID- 10900577
TI  - Treatment with nafarelin for endometriosis in young women. Efficacy, safety and
      lipid metabolism. Niigata Nafarelin Study Group.
AB  - OBJECTIVE: To assess the efficacy, safety and effect on lipid metabolism of
      treatment with nafarelin acetate for clinical endometriosis symptoms in young
      women. STUDY DESIGN: A multicenter, open-label, nonrandomized clinical trial was
      conducted on subjects who were 19-29 years of age with clinical symptoms and
      signs of endometriosis demonstrated by laparoscopy, ultrasonography, magnetic
      resonance imaging, computed tomography or pelvic examination. For 24 weeks, 34
      women received intranasal nafarel, 200 mg twice daily. The main outcome measures
      were changes in signs and symptoms, lumbar bone mineral density by dual energy X
      ray absorptiometry and serum parameters of lipid metabolism. RESULTS: Symptoms
      and signs of endometriosis decreased significantly during treatment and at the
      first posttreatment menses. CA-125 level decreased significantly, from 84.0 +/-
      20.2 U/mL at baseline to 13.4 +/- 1.9 at the 24th week (P = .0014). The mean high
      density lipoprotein cholesterol, total cholesterol, apoprotein A-I and A-II,
      lipoprotein (a) and remnant lipoprotein cholesterol levels significantly
      increased, and cholesterol ester transfer protein activity slightly increased, by
      the 24th week but fell to baseline values by the first posttreatment menses.
      Despite a low mean serum estradiol level (20 pg/mL) at the end of treatment, the
      reported incidence of hot flushes was low (24%), and only one woman withdrew
      because of hypoestrogenic symptoms. CONCLUSION: Twenty-four-week nafarelin
      treatment for clinical endometriosis symptoms in women < or = 29 years was safe
      and effective.

PMID- 10900578
TI  - Myomectomy and tuboplasty performed at the same time in cases of distal tubal
      obstruction with associated fibroids.
AB  - OBJECTIVE: To compare pregnancy rates and outcomes in patients who underwent
      tuboplasty alone versus those who had simultaneous myomectomy and tuboplasty for
      distal tubal occlusion. STUDY DESIGN: One hundred eighty-eight patients underwent
      tuboplasty alone. An additional 56 were treated by both myomectomy and
      tuboplasty, and 8 others underwent tuboplasty, leaving the myomas in situ.
      RESULTS: Of the 188 patients who underwent tuboplasty alone, 47.90% (90 patients)
      became pregnant; of these, 24 (26.7%) had a spontaneous miscarriage, 14 (15.6%)
      developed an ectopic pregnancy, and 52 (57.7%) achieved a viable birth. By
      comparison, of the 56 patients who had both tuboplasty and myomectomy, 53.6% (30
      patients) conceived: of these, 11 (36.7%) miscarried, 7 (23.3%) developed ectopic
      pregnancies, and 12 (40.0%) achieved viable births. Of the eight patients who
      underwent tuboplasty while leaving the myoma in situ, five became pregnant,
      resulting in three viable births (37.5%) and two spontaneous abortions (25%). The
      number of pregnancies, ectopic gestations, miscarriages and viable births in the
      two former groups showed no statistical differences. (For the eight patients with
      the myoma in situ, the number was too small for statistical analysis.)
      CONCLUSION: Because there is no disadvantage to performing myomectomy at the time
      of tuboplasty for distal tubal occlusion, the combined surgical approach should
      be the procedure of choice rather than performing myomectomy in a separate
      operation later.

PMID- 10900579
TI  - Erythromycin for chlamydiasis in pregnant women. Assessing adherence to a
      standard multiday, multidose course.
AB  - OBJECTIVE: To assess patient adherence among pregnant women infected with
      Chlamydia trachomatis given a self-administered, 10-day course of erythromycin
      prescribed as 500-mg tablets to be taken four times a day for the full 10-day
      period of treatment. STUDY DESIGN: Study participants (n = 30) were given the
      standard, 10-day supply of 500-mg tablets of erythromycin and instructed to take
      one tablet four times daily for 10 days. Patients were blinded to the fact that
      the Medication Event Monitoring System was being used and that their adherence to
      this course of drug therapy was being monitored. RESULTS: A 100% cure rate was
      achieved. The average percentage of therapeutic coverage actually achieved by the
      study participants declined with the length of erythromycin therapy. Further, as
      the duration of treatment increased, the longest interval between two successive
      doses of erythromycin also increased. CONCLUSION: This study demonstrated the
      importance of assessing both the quantitative and temporal aspects of self
      administered oral medication when assessing patient adherence. Moreover, since
      the length of the course of antibiotic therapy was shown to affect patient
      adherence, coupled with the 100% cure rate we observed, future research geared
      toward maximizing adherence while minimizing duration of treatment seems
      warranted.

PMID- 10900580
TI  - Indications for labor induction. Differences between university and community
      hospitals.
AB  - OBJECTIVE: To compare the rates of and indications for labor induction between a
      university hospital and two community hospitals and to examine the risk of
      cesarean delivery among labor induction cases. STUDY DESIGN: Labor induction
      cases over a six-month period were included (N = 536). Medical records were
      reviewed by a trained abstractor using a standardized form to determine maternal
      characteristics, reason for induction and perinatal outcomes. RESULTS: Rates of
      labor induction were significantly different between the three hospitals:
      university, 18.2%; community hospital A, 21.4%; community hospital B, 33.7% (P <
      .001). At the university hospital, 95% of labor inductions were medically
      indicated using American College of Obstetricians and Gynecologists (ACOG)
      criteria. Forty-four percent of labor inductions at community hospital A and 57%
      at community hospital B were for elective reasons. Cesarean rates among induction
      cases were highest at the university hospital (19%) as compared to community
      hospital A (15%) and community hospital B (11%), although the difference was not
      statistically significant. Parity, race and cervical status, but not elective
      induction, were significantly associated with cesarean delivery. CONCLUSION:
      Labor induction was more frequent in community hospitals but more likely to meet
      ACOG-approved indications at the university hospital. The more-frequent
      inductions at the community hospitals did not result in higher cesarean rates.

PMID- 10900581
TI  - Second- and third-trimester ultrasound evaluation of chorionicity and amnionicity
      in twin pregnancy. A simple algorithm.
AB  - OBJECTIVE: To develop a simple and systematic algorithm to determine chorionicity
      and amnionicity in the second and third trimester by ultrasound. STUDY DESIGN:
      The algorithm was constructed based upon years of experience in examining
      multifetal pregnancies and by adopting the different sonographic signs suggested
      in the literature. RESULTS: The following parameters were used to construct the
      algorithm: sexing of the fetuses, placental location, and origin, thickness and
      number of layers of the membranes. CONCLUSION: The flow chart developed is simple
      to use and embodies all possible sonographic parameters to help determine
      chorionicity and amnionicity in the second and third trimester.

PMID- 10900582
TI  - Clinical use of nafarelin in the treatment of leiomyomas. A review of the
      literature.
AB  - OBJECTIVE: To review the efficacy and safety of nafarelin in the treatment of
      leiomyomas. STUDY DESIGN: A literature review of published clinical trials was
      conducted. Six studies, including a total of 602 patients with leiomyomas, were
      reviewed. Patients received intranasal nafarelin, 50-400 micrograms twice daily
      for three to six months. Vaginal bleeding patterns, leiomyoma and uterine size,
      surgical conditions and adverse effects were assessed. RESULTS: Nafarelin
      consistently suppressed estrogen production, reduced leiomyoma and uterine size,
      and controlled menorrhagia. The significant reduction in uterine bleeding and
      amenorrhea resulting from administration of nafarelin was associated with a rise
      in mean hemoglobin concentrations. In addition, nafarelin improved hematologic
      parameters in women with and without anemia. Nafarelin was well tolerated,
      although hot flushes were the most commonly reported adverse events. Measured
      bone mineral density decreased significantly during treatment, although by six to
      nine months post-treatment, it increased to values not significantly different
      from baseline. The adverse effects of nafarelin were generally reversible after
      treatment withdrawal. CONCLUSION: Nafarelin treatment of women with symptomatic
      leiomyomas effectively decreases uterine bleeding; improves hematologic
      parameters; manages symptoms of menometrorrhagia, dysmenorrhea and pelvic
      discomfort; reduces uterine and myoma size; and is well tolerated. Reduction in
      bone mineral density occurs, but levels return to, or near, baseline levels
      within six months after treatment.

PMID- 10900583
TI  - Medical management of interstitial pregnancy with a retained IUD. A case report.
AB  - BACKGROUND: Systemic methotrexate therapy for interstitial pregnancy has an
      increased failure rate as compared to other ectopic locations. No case of
      interstitial pregnancy with a retained intrauterine device (IUD) has been
      reported on before. CASE: An asymptomatic, 21-year-old woman presented with a
      positive pregnancy test and a retained IUD. Vaginal ultrasound revealed a left
      interstitial pregnancy. Diagnostic laparoscopy was followed by a single dose of
      methotrexate (50 mg/m2). Five days later, a marked increase in the human
      chorionic gonadotropin level was followed by a second course (four doses) of
      methotrexate, 1 mg/kg, alternating with 0.1 mg/kg of leucovorin. Concomitant
      Chlamydia was treated with azithromycin, and the IUD was expelled spontaneously.
      CONCLUSION: Medical management of interstitial pregnancy may prevent surgery that
      limits future fertility, but the evidence suggests that more than one dose of
      methotrexate may be required.

PMID- 10900584
TI  - Vulvitis attributed to hypersensitivity to estrogen. A report of 11 cases.
AB  - BACKGROUND: Vulvitis that is refractory to all treatment remains a therapeutic
      challenge. Hypersensitivity to progesterone and estrogen has been recognized as a
      rare cause of premenstrual dermatoses. Such hypersensitivity seemed to be the
      cause of vulvitis in the patients described below. CASES: Nine women had
      treatment-resistant cyclic vulvitis and two patients had vulvitis develop after
      commencing hormone replacement therapy (HRT). These patients demonstrated delayed
      type hypersensitivity responses by intradermal testing to endogenous estrogens,
      with two of the patients also reacting to intradermal testing with progesterone.
      A group of 19 healthy control subjects with no history of vulvar symptoms did not
      react to any test substance. Ten subjects with other vulvar dermatoses also did
      not react to any test substance. Of the nine patients with cyclic vulvitis, one
      recovered at menopause, and three responded to therapy aimed at lowering
      endogenous estrogen levels. One was able to control symptoms with a potent
      topical corticosteroid, and four elected not to be treated. Both patients with
      HRT-related vulvitis recovered when HRT was ceased. CONCLUSION: Hypersensitivity
      to estrogen appears to be implicated in chronic, cyclic vulvitis and vulvitis
      related to HRT in these patients. This is the first report of vulvitis due to
      estrogen hypersensitivity. The problem may not be rare and should be considered
      in patients with unexplained cyclic vulvitis unresponsive to standard therapy or
      in those developing noncandidal vulvitis on HRT. Specific therapy aimed at
      suppressing or antagonizing estrogen may be required in these patients.

PMID- 10900585
TI  - Vaginal delivery in a woman with limb-girdle muscular dystrophy. A case report.
AB  - BACKGROUND: Limb-girdle muscular dystrophy is a muscular disease determined
      genetically. Few papers have been published on this disorder in pregnancy.
      Several authors reported on delivery by cesarean section because of the risk of
      dystocia. CASE: A woman with limb-girdle muscular dystrophy had two pregnancies
      with normal vaginal delivery and follow-up. No obstetric complications related to
      the disease occurred. CONCLUSION: A trial of labor is possible in patients with
      limb-girdle muscular dystrophy if no obstetric contraindications exist.

PMID- 10900586
TI  - Preoperative diagnosis of intestinal intussusception in pregnancy. A case report.
AB  - BACKGROUND: Intestinal intussusception is a rare event during pregnancy. The
      diagnosis of intestinal obstruction from any cause in pregnancy is made more
      difficult by the common overlapping complaints of nausea, vomiting and abdominal
      pain, which may persist during the second trimester. CASE: Intestinal obstruction
      occurred at 17 weeks' gestation. A preoperative diagnosis of intussusception was
      made by ultrasound by demonstrating multiple ecodense and ecolucent rings in the
      right lower quadrant of the abdomen. CONCLUSION: Ultrasonography may support the
      diagnosis of intussusception in pregnant women with intestinal obstruction.

PMID- 10900587
TI  - Bowel perforation caused by an endoscopic stapler used during laparoscopically
      assisted vaginal hysterectomy. A case report.
AB  - BACKGROUND: A commonly cited concern regarding laparoscopic hysterectomy is that
      the risks and complications associated with the procedure may be greater than
      those associated with more-traditional hysterectomy techniques. Among the
      potential risks that are unique to this approach are injuries caused by
      laparoscopic instrumentation. The events described below constitute the first
      known case of a postoperative bowel perforation caused indirectly by an automatic
      stapler used during a laparoscopically assisted vaginal hysterectomy (LAVH).
      CASE: A 52-year-old, African American woman underwent an uncomplicated LAVH,
      bilateral salpingo-oophorectomy and anterior repair in January 1995.
      Approximately nine months later, the patient began experiencing abdominal pain
      during a trip to Europe. Her condition progressively deteriorated to the point
      that an emergency landing in Iceland was required during her flight home. The
      patient was found to have a bowel obstruction and underwent a laparotomy and
      bowel resection. An open staple from the endoscopic stapler that was used at the
      time of LAVH was found to have caused the bowel perforation, which eventually
      resulted in adhesion formation and obstruction. CONCLUSION: Every effort should
      be made to remove loose staples from the operative field prior to termination of
      a laparoscopic procedure.

PMID- 10900588
TI  - Association of metformin and pregnancy in the polycystic ovary syndrome. A report
      of three cases.
AB  - BACKGROUND: Infertility is a common manifestation of the polycystic ovary
      syndrome (PCOS), a condition characterized by chronic anovulation,
      hyperinsulinemia and hyperandrogenism. Hyperinsulinemia leads to increased
      ovarian androgen production, resulting in follicular atresia and anovulation.
      Metformin, a medication that improves insulin sensitivity and decreases serum
      insulin levels, restores menstrual cyclicity and ovulatory function and may
      improve fertility rates in women with PCOS. We present three consecutive cases
      from our clinic that support this premise. CASES: Three patients were seen in the
      reproductive endocrinology clinic with documented PCOS, long-standing infertility
      and clinically diagnosed insulin resistance. The first patient had
      hyperandrogenic, insulin-resistant acanthosis nigricans syndrome and had been
      resistant to multiple courses of clomiphene citrate; the second exhibited
      hypertension, hyperlipidemia and glucose intolerance along with anovulation; and
      the third presented with poorly controlled type 2 diabetes and a desire to
      conceive. Each patient received metformin, which led to restoration of menstrual
      cyclicity and conception in all three cases. CONCLUSION: These three patients
      reflect the heterogeneous nature of PCOS, and treating their underlying insulin
      resistance with metformin resulted in pregnancy. These findings suggest that
      metformin may be a useful adjunct for treatment of infertility in patients with
      PCOS.

PMID- 10900589
TI  - Partial follicular aspiration for salvaging an IVF cycle after improper hCG
      administration. A case report.
AB  - BACKGROUND: Failure of oocyte retrieval during in vitro fertilization (IVF) is
      considered "empty follicle syndrome." Many theories have been postulated, some
      related to an underlying ovulatory disorder or premature oocyte atresia. As
      illustrated in this case and in a review of empty follicle syndrome at our
      institution, often it is related to improper administration of human chorionic
      gonadotropin (hCG). CASE: A 40-year-old woman underwent IVF for a 10-year history
      of unexplained secondary infertility. Two ultrasound-guided oocyte retrievals
      were performed 34 hours apart due to improper hCG administration prior to the
      first procedure. The number of oocytes successfully aspirated at the second
      retrieval, fertilization rate and pregnancy outcome were analyzed. Successful
      retrieval of 16 oocytes, all mature and fertilized, occurred subsequent to the
      second oocyte retrieval. No pregnancy was established with the fresh cycle.
      CONCLUSION: This case report supports the premise that an IVF cycle in which
      improper hCG administration occurs can be salvaged. After partial follicular
      aspiration, no ovulation or luteinization of the remaining follicles occurred
      because of continued suppression by the gonadotropin releasing hormone analog. It
      is critical to consider the possibility of improper hCG administration when
      facing failure of oocyte retrieval. The procedure should be terminated and hCG
      readministered, and a second retrieval should be performed 34 hours later.

PMID- 10900590
TI  - Actinomycosis mimicking a pelvic malignancy. A case report.
AB  - BACKGROUND: Pelvic actinomycosis is difficult to diagnose preoperatively. The
      chronic infection is locally infiltrative and causes a profound induration of
      infected tissue planes. This induration, combined with absence of fever and
      leukocytosis, can mimic a pelvic malignancy. CASE: A 55-year-old woman was
      diagnosed with a pelvic mass after a two-month history of intermittent lower
      abdominal pain. The patient had had an intrauterine device for 12 years; it was
      removed two months prior to an exploratory laparotomy for the symptomatic mass.
      The mass was highly suggestive of colorectal cancer, with the rectosigmoid colon
      indurated and adherent to the uterus and sacrum. The induration of the colon
      extended caudally to within 3 cm of the anal verge. An abdominoperineal resection
      was performed along with a total abdominal hysterectomy, bilateral salpingo
      oophorectomy and colostomy. Pathology revealed acute and chronic endometritis,
      left tuboovarian abscess and extensive, acute inflammation of the rectosigmoid
      colon without evidence of diverticuli. Actinomycosis was diagnosed based on the
      characteristic sulphur granules seen on hemotoxylin and eosin staining.
      CONCLUSION: Actinomycosis can mimic pelvic and abdominal malignancies. Surgeons
      should be aware of this infection to potentially spare women morbidity from
      excessive surgical procedures.

PMID- 10900591
TI  - Hand-assisted laparoscopy for megamyomectomy. A case report.
AB  - BACKGROUND: In cases of uterine myomas of massive size, minimally invasive
      laparoscopic or laparoscopically assisted myomectomy techniques are not feasible
      alternatives to traditional laparotomy. This report introduces the use of hand
      assisted laparoscopy, a novel approach that permits the insertion of the hand
      into the abdomen through a glove-sized incision while preserving the
      pneumoperitoneum, as an alternative to laparotomy for patients with massive
      myomas unsuitable for conventional laparoscopic myomectomy. CASE: A 28-year-old
      nullipara requested minimally invasive myomectomy and fertility preservation for
      the treatment of a massively enlarged uterus reaching the level of the liver.
      Myomectomy was safely performed by hand-assisted laparoscopy using the Pneumo
      Sleeve System (Dexterity, Blue Bell, Pennsylvania), a 7.5-cm transverse
      suprapubic incision and a 1-cm umbilical laparoscopic incision. Surgery lasted
      120 minutes, and the estimated blood loss was 250 mL. The total weight of the
      myomas was 3,120 g. The patient was discharged on the second postoperative day
      and had an uneventful recovery. CONCLUSION: The successful outcome of this
      initial case suggests that hand-assisted laparoscopic myomectomy is a feasible
      and safe minimal-access option that could effectively replace routine laparotomy
      in patients with massive uterine enlargement.

PMID- 10900592
TI  - Cervicovaginal psammoma bodies in endosalpingiosis. A case report.
AB  - BACKGROUND: The presence of psammoma bodies on cervicovaginal smears is a rare
      finding. These structures have usually been associated with malignant tumors,
      particularly ovarian carcinoma. However, a review of the literature reveals that
      up to 50% of these patients will have psammoma bodies in association with benign
      conditions; thus, this finding does not always correlate with the presence of a
      malignant tumor. CASE: An asymptomatic, nulliparous woman had psammoma bodies on
      a cervicovaginal smear. Evaluation, including cervical conization, endometrial
      sampling, laparoscopy with pelvic washings and ovarian biopsy, revealed cervical
      intraepithelial neoplasia 1, endosalpingiosis and numerous psammoma bodies in all
      specimens except from the cervix. Follow-up examinations at three and six months
      were negative. CONCLUSION: The finding of psammoma bodies in a Pap smear is not
      always associated with the presence of a pelvic malignancy.

PMID- 10900593
TI  - Promoting mental health in schools in the midst of school reform.
AB  - Efforts to promote mental health in schools have encountered a variety of
      systemic problems. Of particular concern is that planning and implementing
      programs and services often occurs in an unsystematic and ad hoc fashion
      resulting in fragmented and piecemeal activities and an inefficient use of
      limited resources. Even more fundamental is the degree to which schools
      marginalize all efforts to address barriers to student learning. With a view to
      enhancing understanding and resolution of these problems, this paper explores the
      policy deficiencies that perpetuate the status quo and presents a framework for
      moving forward.

PMID- 10900594
TI  - Social and emotional learning: a framework for promoting mental health and
      reducing risk behavior in children and youth.
AB  - Many programs have been developed to help schools enhance students' health and
      reduce the prevalence of drug use, violence, and high-risk sexual behaviors. How
      should educators choose among these? This article describes selection criteria
      based on theory, research, and best educational practice that identify key social
      and emotional learning (SEL) competencies and program features. The SEL
      competencies for students include 17 skills and attitudes organized into four
      groups: awareness of self and others; positive attitudes and values; responsible
      decision making; and social interaction skills. The 11 program features critical
      to the success of school-based SEL programs emphasize curriculum design,
      coordination with larger systems, educator preparation and support, and program
      evaluation. Developed by the Collaborative to Advance Social and Emotional
      Learning (CASEL), the SEL framework can be used to guide selection of research
      based prevention programs that address health, substance abuse, violence
      prevention, sexuality, character, and social skills.

PMID- 10900595
TI  - Primary prevention: educational approaches to enhance social and emotional
      learning.
AB  - The 1995 publication of Goleman's Emotional Intelligence triggered a revolution
      in mental health promotion. Goleman's examination of Gardner's work on multiple
      intelligences and current brain research, and review of successful programs that
      promoted emotional health, revealed a common objective among those working to
      prevent specific problem behaviors: producing knowledgeable, responsible,
      nonviolent, and caring individuals. Advances in research and field experiences
      confirm that school-based programs that promote social and emotional learning
      (SEL) in children can be powerful in accomplishing these goals. This article
      reviews the work of the Collaborative to Advance Social and Emotional Learning
      (CASEL), its guidelines for promoting mental health in children and youth based
      on SEL, key principles, and examples of exemplary programs.

PMID- 10900596
TI  - Effective school-based mental health interventions: advancing the social skills
      training paradigm.
AB  - Psychotherapeutic interventions with children have not been as successful in
      practice as laboratory studies suggest. Two weaknesses frequently cited include
      the failure of treatment gains to generalize to other times and settings and the
      lack of individualization. Although social skills interventions have inherent
      appeal and appear appropriate to address many of the social and emotional
      problems encountered by children and youth, they have not demonstrated
      effectiveness despite their widespread use. This article outlines four steps to
      improve social skills interventions that take advantage of the unique
      environments of schools and increase the likelihood that social skills
      interventions can achieve individualization and generalization.

PMID- 10900597
TI  - Expanded school mental health programs: advancing reform and closing the gap
      between research and practice.
AB  - Expanded school mental health (ESMH) programs provide a range of mental health
      services to youth in special and regular education including prevention,
      assessment, treatment, and case management. Despite the rapid growth of ESMH
      programs in the United States and elsewhere, many communities still do not have
      ESMH programs and those that do exist often fail to implement empirically
      validated intervention and treatment strategies. Systematic prevention efforts
      remain a lauded, yet illusive goal. For ESMH programs to fulfill their promise of
      improved access, increased productivity and improved behavioral outcomes,
      researchers, school-based mental health service providers, and educators must
      work together to move child mental health programs beyond limiting constructs and
      approaches. These issues are reviewed and an example of an "ideal" approach to
      implement best practices in schools and close the gap between research and
      practice is offered.

PMID- 10900598
TI  - Implementing and maintaining school-based mental health services in a large,
      urban school district.
AB  - The Dallas (Texas) Public Schools established the first school-based health
      center in the United States in 1969. In 1993 a partnership between two school
      principals, a school mental health professional, and the medical director of the
      county mental health center was the impetus for the first comprehensive school
      based mental health center in Texas. In 1995 the programs joined together as
      Youth and Family Centers (YFCs) to provide physical health, mental health, and
      other support services to students and their families. The 10 strategically
      located school-based centers are directed by licensed mental health professionals
      employed by the district who lead a multidisciplinary team of physical health and
      mental health providers. Students served by the YFCs have fewer discipline
      problems, course failures, and school absences.

PMID- 10900599
TI  - Overcoming challenges in outcome evaluations of school mental health programs.
AB  - Significant growth and improvement of school mental health programs has occurred
      in recent years. However, evaluation of outcomes for children receiving these
      services is needed to provide accountability data and ensure the sustainability
      of these programs. When designing studies, evaluators must overcome several
      challenges that may threaten the validity of their conclusions. In this paper,
      threats or challenges to the internal and external validity of results from
      evaluation studies are reviewed. Suggestions are provided for overcoming these
      challenges, in order to encourage future evaluation activities in this developing
      field and to document the impact of services for youth and their families.

PMID- 10900600
TI  - Toward ending the marginalization and fragmentation of mental health in schools.
AB  - For efforts to address mental health and psychosocial concerns in schools to be
      effective, practices must not be marginalized and must be implemented cohesively
      at each school and among families of schools. Mechanisms and processes must be
      established to minimize marginalized and fragmented practice, weave together
      school and community resources, and develop comprehensive and multifaceted
      approaches. A school-based, resource-oriented team represents one key mechanism.
      In addition, schools working in the same neighborhoods and with the same families
      can use a collaborative council to coordinate school and community resources.
      Resource team and collaborative council functions include mapping, analyzing, and
      redeploying existing resources, and formulating plans for evolving a
      comprehensive, multifaceted continuum of school-community interventions to
      address barriers to student learning and promote healthy development.

PMID- 10900601
TI  - Sharing the vision: healthy, achieving students what can schools do?

PMID- 10900602
TI  - [Role of cytokines and chemokines in the non-progression of HIV infection in
      vertically infected children].
AB  - BACKGROUND: To study the cytokine production in vertically HIV-1-infected
      children with more of 7 years of HIV infection and different pattern of
      progression. PATIENTS AND METHODS: We study 32 HIV-1-infected children: 8 NA
      children (age > 7 years, asymptomatic or with light symptoms, without
      antiretroviral treatment and TCD4+ > 25%); 10 NE1 children (> 6 years,
      symptomatic, with antiretroviral treatment and TCD4+ > 25%); 14 NE2-3 children (>
      6 years, symptomatic, with antiretroviral treatment and TCD4+ < 25%) and 16 (C)
      controls, children non-VIH+. The peripheral mononuclear cells of HIV-infected
      children (PBLs) were cultivated and cytokine production was quantified in the
      supernatant. RESULTS: The non-stimulated PBMC from HIV-infected children produced
      more TNF-alpha and less IL-2 that C-group. The production of IFN-gamma was lower
      in the groups NE1 and NE2-3 than in C-group. The production of IFN-gamma was
      higher in group NA than in NE2-3. In the phytohaemagglutinin (PHA) stimulated
      PBLs, the production of TNF-alpha was higher in NA and NE1 than in controls. The
      production of IL-2 was similar in NA and NE1 than in controls. The production of
      IL-2 was similar in NA and NE1 than in control group, but the groups NE2-3
      produced less IL-2 than control and NE1 groups. The production of IFN-gamma and
      RANTES were significantly higher in NA than in controls. The groups NE1 and NE2-3
      produced lower levels of IL-5 than control and NA groups. The groups NE2-3
      produced lower levels of IL-10 than control group. The ratio IFN-gamma/IL-5 and
      IFN-gamma/IL-10 were higher in group NA than in control and NE1. CONCLUSIONS: In
      non-progressors HIV-infected children the immune response is conserved and we
      have observed an increased Th1 response, while in progressors HIV-infected
      children receiving antiretroviral treatment we could observe a diminished Th2
      response. Moreover, our data clearly indicate that the decrease of IL-2 is an
      early marker of HIV-infection.

PMID- 10900603
TI  - [Validity of the King's Health questionnaire in the assessment of quality of life
      of patients with urinary incontinence. The King's Group].
AB  - BACKGROUND: To assess the validity of the Spanish version of the King's Health
      Questionnaire (KHQ) for measuring the quality of life of women with different
      types of urinary incontinence. PATIENTS AND METHODS: 77 women with urinary stress
      incontinence (USI), 51 with urge incontinence (UUI) and 34 with mixed urinary
      incontinence (MUI) were consecutively recruited. Subjects were diagnosed using
      urodynamic tests. Patients completed the KHQ and SF-36 questionnaires on
      inclusion in the study, after 15 days, and again after one month. RESULTS: There
      were no significant differences in socio-demographic and QOL characteristics
      between different UI groups. UUI and MUI patients had greater urinary frequency
      and urge than USI patients, and USI and MUI patients had a greater number of
      leakage episodes than UUI patients. Correlations between dimensions on the KHQ
      and the SF-36 were moderate to strong. Women with greater urinary frequency,
      greater urgency, more incontinence episodes during the week and who used pads and
      nappies perceived a worse quality of life. Changes in these variables correlated
      with changes in HRQOL. The internal consistency of dimensions was good (0.65
      0.92) as was test-retest reliability (0.68-0.88). Dimensions most sensitive to
      change after one month of treatment were impact of UI, seriousness of UI, and the
      symptoms scale (effect size greater than 0.6). CONCLUSION: The KHQ is a valid
      instrument for measuring the quality of life of patients with different types of
      UI. Improvements in urinary frequency, urinary urgency, number of leakage
      episodes, and changes in the type of protective material produces an increase in
      HRQOL.

PMID- 10900604
TI  - [Evolution of the new number of diagnoses of HIV infection in Asturias, Navarra
      and La Rioja].
AB  - BACKGROUND: To describe the time-trend of people diagnosed with HIV infection in
      Asturias, Navarra and La Rioja up to 1998. METHODS: HIV case reports since the
      beginning of the epidemic have been analysed. Only the first positive confirmed
      result for each patient was taken into account. RESULTS: In the three regions a
      total of 7,870 HIV infections had been diagnosed by 1998 (4 cases per 1,000
      inhabitants). New diagnoses decreased 60% since 1991 to 1998, with the greatest
      fall among intravenous drug users, and the lowest fall in sexually transmitted
      infections. CONCLUSIONS: This time-trend supports a reduction in HIV transmission
      in these three regions; however, the number of new diagnosed infections remains
      high.

PMID- 10900605
TI  - [Cancer of the cervix uteri and impact of HIV on its development in socially
      disadvantaged young women].

PMID- 10900606
TI  - [Smoke intoxication in fires: antidote treatment with vitamins].

PMID- 10900607
TI  - [Whooping cough in adolescents and adults. Epidemiology and implications for
      vaccination].

PMID- 10900608
TI  - [Immunologic changes associated with tics, compulsive-obsessive disorder, and
      PANDAS].

PMID- 10900610
TI  - [Physiopathology of acute carbon monoxide poisoning].

PMID- 10900609
TI  - [Prolonged fever in a 78-year-old woman with chronic myelocytic leukemia].

PMID- 10900611
TI  - [Budd-Chiari syndrome treated with transluminal angioplasty in a patient with
      Behcet's disease: long-term follow-up].

PMID- 10900612
TI  - [Chlorambucil in the treatment of secondary amyloidosis].

PMID- 10900613
TI  - [Revisions in the WHO histological classification of urothelial bladder tumors
      and flat urothelial lesions].
AB  - Recently the World Health Organization published a new classification of urinary
      bladder tumors which is intended to take into account better the biology of the
      various lesions and to better distinguish between clearly benign and malignant
      lesions. We examine the possible diagnostic and clinical impact of the new
      classification, including recent immunohistochemical findings. Papillary
      urothelial lesions include papillomas, papillary neoplasms of low malignant
      potential, and papillary carcinomas. Flat urothelial lesions include hyperplasia,
      reactive atypia/atypia of unknown significance, dysplasia, and carcinoma in situ.
      Invasive patterns of papillary carcinomas are discussed, with special emphasis on
      lamina muscularis mucosae substaging. The most important feature of the new
      classification is its differentiation of two types of low-grade, noninvasive
      papillary urothelial lesions: papillary neoplasm of low malignant potential vs.
      papillary carcinoma. Long-term follow-up studies are needed to determine the
      clinical significance of this differentiation.

PMID- 10900614
TI  - [PCR based diagnosis in pathology].
AB  - PCR-based diagnosis of infectious diseases has developed into an important method
      in surgical pathology. We summarize our experience in this area based on 3500
      analyses performed during the past 5 years. The peculiarity of material from a
      pathological laboratory is the risk of DNA fragmentation as a consequence of
      tissue fixation. For this reason the assays used must be adapted to this
      particular situation. PCR-based diagnosis of infectious diseases, if performed
      according to appropriate quality standards, is a safe and effective technique
      with high sensitivity and specificity and results in an etiologically based
      diagnosis.

PMID- 10900615
TI  - [Sideroelastosis of pulmonary vessels after welder dust exposure].
AB  - Sideroelastosis pulmonum was first described by Ceelen (1931) and Gellerstedt
      (1939), mentioning an idiopathic type, but also vascular alterations in chronic
      pulmonary congestion. We analysed the question wether secondary sideroelastosis
      can be demonstrated also in lungs after previous welder dust exposure. Lung
      samples of 43 patients and deceased with various exposure periods to welder dust
      were investigated. On each sample, light microscopical, scan electron
      microscopical and energy dispersive x-ray micro analyses (EDX) were performed. In
      six samples (14%) vascular alterations in the area of denaturated elastic fibres
      with siderophilic "impregnation" were seen, corresponding to the features
      described by von Ceelen and Gellerstedt. Giant cell or granulomatous reactions,
      however, were present only in exceptional cases. This phenomenon was seen mostly
      in cases of marked local siderin deposits and reactive fibrosis. Using EDX, a
      number of metals characteristic for welder dust (Al, Ti, Cr, Ni) as well as iron
      were found in siderophages. No other metal than iron was detected in siderophilic
      elastic fibres using EDX. Causal pathogenetically, a correlation between
      increased iron uptake connected with welding particles and sideroelastosis of the
      vessel walls has to be established. However, in formal pathogenesis, other
      factors such as local perfusion disturbances due to fibrotic processes after
      exposure to harmful substances must be taken into consideration.

PMID- 10900616
TI  - [Advanced breast biopsy instrumentation (ABBI). Histopathologic evaluation of a
      new investigation method].
AB  - The ABBI (advanced breast biopsy instrumentation) system has only recently been
      available for diagnostic excisional biopsy of small, non-palpable lesions of the
      breast. Between 1.1.1998 and 31.3.1999 this method was utilized in 40 patients
      with suspicious microcalcifications (n = 25), newly developed densities (n = 11)
      and a combination of microcalcifications and densities (n = 4). In 12 cases
      malignancy was diagnosed, in 11 cases a subsequent resection was performed. In
      every case sufficient tissue for diagnosis was obtained, in not a single case the
      diagnosis had to be revised in case of subsequent resection. Orientation within
      the specimen is accurate, the resection margins can be judged unequivocally. Any
      necessary special examinations can be performed on the resected tissue. In our
      experience, ABBI is a valuable and elegant tool for diagnosing small suspicious
      lesions of the breast.

PMID- 10900617
TI  - [Autopsy techniques in congenital heart defects. Influence of prenatal diagnosis
      on the planning and carrying out of autopsies].
AB  - As a result of the quality of prenatal ultrasound and the expanded experience of
      prenatal diagnosticians, it is possible to observe congenital heart malformations
      in increasingly greater detail and at an ever earlier stage of gestation [4].
      Since it is on the basis of ultrasound findings that decisions to terminate
      pregnancies are made, it is of cardinal importance that after termination
      monitoring and confirmation of the prenatal diagnosis be carried out. This need
      can only be adequately met by autopsy. There are different methods for carrying
      out autopsies when there is suspicion of a congenital heart defect: a) the
      Anderson sequential segmental analysis as modified according to the Berlin
      method; b) use of a special autoptic method corresponding to the ultrasound
      findings, based on defining a preferred sectional plane; c)
      stereomicroscopically; or d) microscopically after embedding and preparation of
      serial microscopic sections. For the pathologist the consequence is that he has
      to adapt his autopsy method to the ultrasound findings and the age of the fetus.
      This enables him to determine an optimal, case-based autopsy strategy for each
      type of cardiac defect, which is essential for monitoring of the prenatal
      diagnosis. The present paper discusses the various autoptic methods used in cases
      of congenital heart malformations and the consequences for the pathologist of the
      continuing improvements in prenatal diagnostics.

PMID- 10900618
TI  - [Pulmonary microcalcification with miliary foreign-body granulomas. Residuals of
      cured Pneumocystis carinii pneumonia in AIDS].
AB  - Pneumocystis carinii pneumonia (PCP) is one of the most frequent infectious lung
      diseases in immunocompromised patients, especially in AIDS cases. The present
      case report describes pulmonary miliary microcalcifications with and without
      foreign-body reaction in a patient with successfully treated PCP who was known to
      have AIDS. This form of residues of completely healed PCP tends to be rare. Other
      infectious granulomas, foreign-body granulomas and sarcoidosis must be
      differentially diagnosed. After cautious decalcification, pneumocysts can be
      demonstrated with methamine silver (Grocott). It is important to be aware that
      PCP can also undergo spontaneous cure, so that miliary microcalcifications may
      then be the sole pointer to the presence of AIDS.

PMID- 10900619
TI  - [Papillary fibroelastoma of the aortic valve coincident with a cystic tumor of
      the atrioventricular node].
AB  - We describe a rare case of a papillary fibroelastoma of the aortic valve
      occurring simultaneously with a cystic tumor (a so-called mesothelioma) of the
      atrioventricular nodal region. At autopsy the tumor was found to prolapse into
      and occlude the right coronary ostium, leading to an acute, recurring myocardial
      infarction. Histological examination of the grossly unremarkable conduction
      system of the heart revealed a cystic tumor in the region of the atrioventricular
      node. To our knowledge, this is the first report of co-existence of these two
      rare cardiac tumors.

PMID- 10900620
TI  - [POEMS syndrome--a case report].
AB  - One rare case of POEMS syndrome is presented. In a 39-year-old male patient a
      progressive numbness in hands and feet developed within 5 years. Admission with
      increasing dyspnoea and lower leg edema. In swollen inguinal lymph nodes a
      lymphadenopathy with angiofollicular hyperplasia and vascular-plasmacellular
      proliferation was diagnosed and classified as Castleman-like histologic features.
      In os ilium an osteosclerotic plasmocytoma with restriction of kappa light chains
      was found. Potential pathomechanism of POEMS syndrome are discussed.

PMID- 10900621
TI  - [Angiomyolipoma of the lung].
AB  - We present a case of a 48 year old man who complained of progressive dyspnoea.
      Radiograph revealed a large tumor in the left lung. Biopsy was performed and
      revealed beneath a normal bronchial epithelium polymorph tumor cells admixed with
      some histiocytes. These tumor cells were strongly pigmented and expressed HMB-45
      and protein S-100 immunohistochemically. Malignant melanoma of the bronchus was
      included in the differential diagnosis. A thoracotomy and left lower lobe
      resection was performed. Histology revealed an angiomyolipoma. The lung is an
      uncommon localisation of angiomyolipoma with so far three reported cases. Lipoma,
      leiomyoma and lymphangioleiomyomatosis have to be included in the differential
      diagnosis. The peculiarity of this case is the presence of multiple pigmented
      tumor cells that express HMB-45. This has not been reported yet.

PMID- 10900622
TI  - Tomorrow's artificial hand.

PMID- 10900623
TI  - Bioartificial nerve graft for bridging extended nerve defects in rat sciatic
      nerve based on resorbable guiding filaments.
AB  - A long defect (15 mm) in rat sciatic nerve was repaired with a bioartificial
      nerve graft composed of a silicone tube and seven synthetic filaments of five
      types (polyamide, catgut, polydioxanone, and two types of polyglactin, normal and
      quickly-absorbed) inserted longitudinally into the tube. In all cases in which
      filaments were used a regenerating bridge was obtained in the tube after three
      months in contrast to empty silicone tubes, in which no structure was observed.
      There was a 6%-46% recovery of isometric muscle contractility of the anterior
      tibial and gastrocnemius muscles with positive pinch reflex test in most cases.
      Myelinated axons were seen in the regenerating tissue between the filaments but
      not directly in contact with them, and there were varying numbers of macrophages
      close to the filaments. Silicone tubes with filaments, regardless of type of
      filament, induced nerve tissue to regenerate and resulted in functional recovery
      through a 15 mm nerve gap not achieved with empty tubes. Nerve promoting factors
      may be applied to the filaments and the model is a valuable tool for further
      development of artificial nerve grafts.

PMID- 10900624
TI  - Changes in blood flow during one stage lengthening of bone: an experimental study
      in rats.
AB  - Distraction osteogenesis is a well-accepted method of bone lengthening. Its
      disadvantages, however, are that it requires an external fixator and takes a long
      time. One-stage lengthening therefore offers certain advantages. A first point of
      reference for the safe limits of this procedure might be the changes of blood
      flow, and this is also the crucial factor in deciding on the appropriate method
      of lengthening, particularly where the hand or foot is involved. Using a laser
      Doppler flowmeter we measured blood flow in the dorsum of the foot after using
      bilateral minimonofixators to lengthen the tibias of 15 Sprague-Dawley rats. They
      were lengthened in four stages: stage 0 (before lengthening); stage I--12.5%;
      stage II--25%; and stage III--31.25% of lengthening. The blood flow during stage
      I decreased to 79% compared to that of stage 0; 16% during stage II; and 1%
      during stage III. This study suggests that the maximal permissible extent of
      lengthening might be less than a quarter according to the blood flow as suggested
      by this animal model.

PMID- 10900625
TI  - Angiographic study of the subdermal plexus: a preliminary report.
AB  - The subdermal plexus was pictured angiographically in five fresh cadavers
      injected systemically with a lead oxide-gelatin mixture. Subdermal plexus was
      found either in the subdermal plane or in the deep part of the dermis. Diameters
      of vessels in the subdermal plexus are not uniform and there are differences in
      vascular continuity, which means that the subdermal plexus does not always have a
      random pattern. This observation is important when designing a thin flap.

PMID- 10900626
TI  - Three-dimensional computed tomography in evaluation of ankylosis of the
      temporomandibular joint.
AB  - Ankylosis is an uncommon disease of the temporomandibular joint (TMJ), the
      effective treatment of which requires detailed preoperative evaluation of the
      type and extent of the deformity. As well as lateral radiographs and computed
      tomography (CT), three-dimensional CT has been introduced to improve the
      preoperative evaluation. We present six patients with ankylosis of the TMJ who
      were evaluated by three-dimensional CT before and after condylectomy.
      Preoperative findings were compared with operative findings. Three-dimensional CT
      provides a detailed three-dimensional image of the TMJ non-invasively and we
      suggest that it is a valuable tool for evaluation of ankylosis in the TMJ.

PMID- 10900627
TI  - Reconstruction of orbicularis oris and levator labii superioris muscles in
      secondary repair of unilateral cleft lip.
AB  - We devised a new method to repair the depression of the nasal floor and
      inferolateral displacement of the alar base and to reconstruct the philtrum in
      the secondary repair of unilateral cleft lip. Depression of the nasal floor and
      inferolateral displacement of the alar base were corrected by advancing a lump of
      the levator labii superioris, the levator labii superioris alaeque nasi, and the
      upper part of the superficial orbicularis oris muscles to the anterior nasal
      spine. When the depression of the nasal floor was too severe to repair using
      these muscles only, a cranially-based de-epithelialised flap of the scar region
      on the upper lip was inserted under the nasal floor. The lower, greater part of
      the superficial orbicularis oris muscle was dissected to the nasolabial fold,
      brought towards the midline, and laid on the surface of the same muscle on the
      medial side to be sutured. When the depression of the nasal floor was not severe,
      the lower, greater part of the superficial orbicularis oris muscle was passed
      through a tunnel pierced beneath the de-epithelialised scar tissue and sutured to
      the corresponding components on the medial side to reinforce the philtral ridge.
      In both cases, if the deep orbicularis oris muscle in the vermilion had been
      interrupted, it was reconstructed by end-to-end anastomosis. Operative results
      were evaluated in 76 patients using photographs taken preoperatively and
      postoperatively. Elevation of the nasal floor and correction of the alar base
      were achieved in most patients, while reconstruction of the philtrum was achieved
      in cases in which the skin tension at the suture line was weak.

PMID- 10900628
TI  - A retrospective study of speech development in patients with submucous cleft
      palate treated by four operations.
AB  - Fifty patients with submucous cleft palate (SMCP) who had had four different
      operations were reviewed. The operations were pushback palatoplasty (n = 18),
      pharyngeal flap (n = 21), pushback palatoplasty combined with a pharyngeal flap
      (n = 8), and Furlow palatoplasty (n = 3). Postoperatively the speech of 8, 19, 7,
      and 2 patients, respectively, improved so that it was within normal limits. A
      secondary pharyngeal flap was done for six patients, each of whom had previously
      had a pushback palatoplasty. They all improved, five achieving relatively normal
      speech, and one good speech. No patient developed hyponasality or airway
      compromise associated with the pharyngeal flap. The results show that pharyngeal
      flap and pushback palatoplasty combined with a pharyngeal flap seem to be more
      reliable procedures than pushback palatoplasty for patients with SMCP.

PMID- 10900629
TI  - Correction of cleft lip nasal deformity in Orientals with a cantilevered iliac
      bone graft.
AB  - We describe our technique for correcting a nasal deformity associated with cleft
      lip in oriental people. Cantilevered iliac bone grafts are used to provide
      additional structural support and to achieve the desired nasal projection and
      profile. Augmentation of the nasal bridge creates the illusion of a narrower
      nose. This technique was used in 20 patients with severe nasal deformities.
      Clinically and radiographically it consistently produced good, long-lasting
      results.

PMID- 10900630
TI  - Ulnar neuropathy at the elbow: clinical and electrophysiological outcome of
      surgical and conservative treatment.
AB  - The objective was to evaluate and compare the clinical and electrophysiological
      outcome of treatment in patients with ulnar neuropathy at the elbow in 32
      consecutive patients who were studied prospectively. Based on the
      electrophysiological findings 15 patients were treated by surgical decompression
      and 17 were treated conservatively. Sensory and motor nerve conduction studies
      across and below the elbow were done in all patients before treatment and again
      after one year. Postoperatively 10/15 patients (67%) improved clinically and 12
      patients (80%) had improved nerve conduction results. There was clinical and
      electrophysiological agreement in eight patients in the surgically-treated group,
      all of whom improved both clinically and electrophysiologically. In the
      conservatively-treated group six patients (35%) showed clinical improvement, 10
      patients had no improvement, and one patient was worse. The nerve conduction
      studies improved in six patients (35%), were unchanged in eight patients, and
      worse in three. There was clinical and electrophysiological agreement in 11
      patients. We conclude that the electrophysiological examination was valuable in
      deciding which patients to operate on, and that most of the patients improved
      clinically or electrophysiologically postoperatively.

PMID- 10900631
TI  - Osteosynthesis of intra-articular fractures in the proximal interphalangeal joint
      with Kirschner wires.
AB  - Twenty-eight consecutive patients, aged 4-68 years, who had had an intra
      articular fracture of the proximal interphalangeal (PIP) joint were reviewed
      retrospectively in 1996. All patients were operated on within a median of three
      days (range 0-26). Only three patients had open injuries while 11 had fracture
      dislocations. A median of half the articular surfaces were involved, and
      dislocations ranged from 1-4 mm. Twelve patients had their fractures anatomically
      reduced and 13 had postoperative dislocations of less than 1 mm. Eighteen
      patients were reviewed after 10-49 months, and four were interviewed by
      telephone. The median reduction in range of movement in the PIP joint at follow
      up was 15 degrees (range 0-90 degrees). Nine patients had subjectively slightly
      reduced movements, and only three of 17 patients stated that they had limited
      movement. Ten patients had occasional pain, which eight described as mild and two
      as moderate. Two patients had ulnar instability less than 5 degrees, and the
      remainder were stable. Twelve patients had a cold sensation in the affected
      finger joint in cold weather. No patients had changed occupation as a result of
      their injury, and only two patients said that they were limited in any way in any
      activity at work or at home. Open and precise reduction and osteosynthesis with
      Kirschner (K) wires seems to be an effective treatment for most intra-articular
      fractures of PIP joints.

PMID- 10900632
TI  - Results after surgery for severe Dupuytren's contracture: does a dynamic
      extension splint influence outcome?
AB  - Seventy-six consecutive patients were operated on for advanced Dupuytren's
      contracture and the results evaluated after nine months with special reference to
      the use of a dynamic extension splint. The patients were separated into three
      groups: those in whom the splint was used according to our guidelines (n = 15);
      those in whom the splint was used, but inadequately (n = 15); and those who did
      not require splinting (n = 24). Our results nine months postoperatively were
      similar to those of other studies in showing that the fifth proximal
      interphalangeal joint constituted the greatest problem. Comparison of the three
      groups indicated that splinting the way we used it did not influence the natural
      course of the disease after operation.

PMID- 10900633
TI  - Comparison of intramedullary fixation and percutaneous pinning of displaced and
      comminuted Colles' fractures: a prospective and consecutive study.
AB  - This consecutive study comprised 86 patients who were available for follow up 5
      51 months after sustaining a Colles' fracture--Older type IV. A total of 42
      patients were treated with Kirschner (K) wires of whom one had bilateral
      fracture. Forty-four patients (of whom two had bilateral fractures) were treated
      with Rush nails. A functional assessment of the patients was made using both a
      questionnaire and a clinical examination. The end-results of residual deformity,
      subjective and objective findings, and complications were evaluated according to
      the Lucas' modification of the Sarmiento demerit point-rating system. At follow
      up, the ulnar/radial deviation was significantly better in the patients operated
      on with K-wires (37 degrees compared with 27 degrees, p < 0.02, range in both
      groups 0-80 degrees), but no differences were found in the other directions of
      movement. A total of three patients (7%) developed complications. The final
      result showed that 40 (93%) of the fractures treated with K-wires were excellent
      or good compared with 38 (86%) of those operated on with a Rush nail. One
      fracture in each group (2%) had a poor outcome. Comparison of the final results
      showed no significant difference between the two groups.

PMID- 10900634
TI  - Immediate breast reconstruction in two stages using anatomical tissue expansion.
AB  - Over the last four years, 43 modified radical mastectomies and 13 simple
      mastectomies were done for 56 patients with breast cancer followed by immediate
      reconstruction in two stages using anatomical tissue expansion. In 49 patients a
      permanent prosthesis was successfully implanted while three patients refused a
      further operation, and four required removal of the expander. Complications were
      seen in 21 cases, including infection (n = 4), Baker III-IV contractures (n = 5),
      radiodermitis with breast distorsion (n = 3), and seroma (n = 2). Four patients
      required removal of the expander, and no further attempts were made to
      reconstruct the breast. All 10 patients given radiotherapy developed some kind of
      complication. After a mean follow up of 2.5 years (range 6-48 months), the
      aesthetic result was rated 6.9 and patient satisfaction 7.8 on a 0-10 scale. We
      concluded that immediate breast reconstruction with anatomical tissue expansion
      gives predictable aesthetic results, which satisfied most patients. Although the
      complication rate is high, it does not exceed complication rates associated with
      mastectomy alone or delayed reconstruction. At present, only patients undergoing
      preoperative or postoperative radiotherapy and hesitant patients are not
      considered to be candidates for this procedure.

PMID- 10900635
TI  - Ear lobe reconstruction with a posterior ear flap. Case reports.
AB  - We describe a technique for reconstruction of the ear lobe. Although there are
      many procedures that aim to reconstruct the ear lobe naturally, the aesthetic
      results of using a posterior ear flap are better because the scar tissue that
      remains behind the ear is invisible.

PMID- 10900636
TI  - Salvage of an ischaemic lower limb and a free flap with an arterial Y-graft. Case
      report.
AB  - A defect of the lower limb was treated with a scapular free flap. An end-to-side
      anastomosis was made to the posterior tibial artery, which was the single
      perfusing artery of the foot. When it thrombosed, the problem was solved
      successfully with an arterial Y-graft.

PMID- 10900637
TI  - Atypical compression of the deep branch of the ulnar nerve in Guyon's canal by a
      ganglion. Case report.
AB  - A 61-year-old woman with an ulnar claw-finger deformity but no sensory loss had a
      cystic lesion excised from Guyon's canal. The ganglion was in zone 1 of the
      canal, which is associated with both motor and sensory deficit, but on this
      occasion it caused motor dysfunction alone.

PMID- 10900638
TI  - Well-differentiated liposarcoma of the hand. Case report.
AB  - Malignant lipomatous tumours of the hands are extremely rare. A 62-year-old man
      complained of an enlarging, soft, painless mass in his left hand. Magnetic
      resonance imaging showed a fatty tumour with irregular septa, and an incisional
      biopsy showed it to be a well-differentiated liposarcoma. The tumour was resected
      en bloc and he had a course of external beam radiotherapy. Apart from a slight
      reduction in grip strength he was well 15 months later with no sign of
      recurrence.

PMID- 10900639
TI  - Scapholunate dissociation caused by gouty arthritis of the wrist. Case report.
AB  - Gouty arthritis of the wrist is rare, and may be associated with scapholunate
      dissociation. To our knowledge, only two cases have been reported so far. In this
      report, we describe a 40-year-old patient with scapholunate dissociation caused
      by acute gouty arthritis of the wrist. His clinical findings and radiographs
      mimicked infectious arthritis or osteomyelitis of the carpal bones.

PMID- 10900640
TI  - [Cryoglobulinemic nephritis associated with chronic HCV infection].

PMID- 10900641
TI  - [Ways to inhibit development of chronic renal failure].

PMID- 10900642
TI  - [Possible mechanisms of polyuria in progressive chronic renal failure].
AB  - AIM: Elucidation of the role of saluresis and osmotic diuresis in renal function
      of patients with chronic renal failure. MATERIAL AND METHODS: The trial included
      68 subjects, among them 25 patients with chronic renal failure (CRF) of the third
      and fourth degree aged 16 to 72 years. Enzyme immunoassay was used to measure
      osmolality, sodium, potassium, magnesium, calcium and creatinine concentrations
      in the serum and urine as well as urine prostaglandin E2. RESULTS: Renal function
      was studied in CRF patients with a 75-90% fall of glomerular filtration rate.
      Creatinine clearance was 19.9 +/- 0.96, it varied in different patients from 10.6
      to 29.7 ml/min. It is shown that diuresis does not correlate with the total ion
      excretion (Na+ plus K+)(r = 0.946, p < 0.0001). A correlation was found between
      excretion of these ions and Mg2+ ions this indicating location of reabsorption
      reduction in the thick ascending limb of Henle loop. In CRF patients (Na+ plus
      K+) excretion correlated with PGE2 excretion (r = 0.65, p < 0.0001). CONCLUSION:
      It is suggested that at this stage of chronic renal failure the mechanism of a
      diuresis increase is not due to osmotic diuresis but rather to secretion of
      prostaglandin E2 which inhibits cation reabsorption and stimulates diuresis.
      Differences are considered between osmotic diuresis and different types of
      saluresis; their possible mechanisms are discussed.

PMID- 10900643
TI  - [Primary focal segmental glomerulosclerosis: clinical and morphological
      prognostic factors].
AB  - AIM: To retrospectively analyze clinical course and results of immunodepressive
      therapy of patients with primary focal-segmental glomerulosclerosis (FSGS), to
      reveal prognostic factors of the disease progression and patients' sensitivity to
      immunosuppressive therapy. MATERIAL AND METHODS: Morphological diagnosis was
      specified, morphological indices of activity and sclerosis were estimated, renal
      survival was analysed, mono- and multivariate analysis of prognostic factors was
      made by the evidence obtained in the study of 135 biopsy specimens from CRF
      patients meeting the criteria of FSGS. RESULTS: At the moment of the disease
      onset only age of the patients was related to FSGS: 5- and 10-year survival was
      100% if the disease started under 16 years of age, if older--the survival was 80
      and 65%, respectively. Nephrotic syndrome, hematuria, high creatinine, racemose
      alterations in the glomeruli worsened the disease prognosis. When cytostatics and
      corticosteroids were used in combination they produced better results and were
      associated with better prognosis than each of them in monotherapy. Patients with
      marked hematuria and low proteinuria were less sensitive to therapy than those
      with weak hematuria and high proteinemia. Patients with FSGS having high IA and
      SI required more aggressive therapy for response. CONCLUSION: Renal biopsy with
      quantitation of IA and IS increases the prognosis accuracy and is important for
      choice of the treatment policy in patients with primary FSGS.

PMID- 10900644
TI  - [Tests for cell membrane destabilization in assessing activity-progression of
      chronic glomerulonephritis].
AB  - AIM: To study the role of cell membrane destabilization (MD) in the serum and
      urine in assessing activity/progression of primary chronic glomerulonephritis
      (CGN). MATERIAL AND METHODS: The trial entered 163 patients (mean age 38 +/- 7.3
      years) with primary CGN in active phase, 64 patients with CGN in remission and 24
      controls. The groups were compared by MD (urine phospholipids--PL, blood and
      urine ethanolamine--EA), indexes of activity and sclerosis (AI and SI), lipid
      peroxidation (LPO), etc. RESULTS: In active glomerulonephritis (GN) vs inactive
      one there were high levels of 24-h proteinuria, AI, PL and EA in the urine,
      malonic dialdehyde (MDA) and hydroperoxides (HP) in the blood. SI was similar in
      both groups. In active GN significant correlations were found between urinary SI,
      systolic and diastolic pressure, elevated levels of beta-lipoproteins and
      triglycerides; between blood EA and 24-h proteinuria, blood platelets, beta
      lipoproteins, triglycerides, MDA, urine EA. CONCLUSION: LPO and MD play an
      essential role in GN pathogenesis. They reflect activity of inflammation in GN
      irrespective of the activity type and clinicomorphological form of GN, absence or
      presence of CRF.

PMID- 10900645
TI  - [Antibacterial drug resistance of gram-negative agents causing urinary infections
      in female outpatients in Russia: results of multicenter study].
AB  - AIM: To investigate the spectrum of gram-negative agents causing acute and
      recurrent cystitis in outpatients and sensitivity of uropathogenic E. coli to
      antibacterial drugs; to compare drug resistance of uropathogenic E. coli isolated
      in Russia and other countries. MATERIAL AND METHODS: The spectrum of gram
      negative bacteria was identified in 299 cases of acute and recurrent cystitis in
      Moscow, Smolensk and Novosibirsk. 271 E. coli uropathogenic strains were examined
      according to CA-SFM and NCCLS criteria for sensitivity to ampicilline,
      gentamycin, trimetoprim, co-trimoxasol, nitrofurantoine, nalidixic acid,
      pipemidine acid, norfloxacine, ciprofloxacine, nitroxoline. RESULTS: E. coli, K.
      pneumoniae, K. oxytoca, P. mirabilis, P. vulgaris caused acute and recurrent
      cystitis in 90.6, 6.4, 1, 1.7, 0.3% of the examinees, respectively. For Moscow
      relative agents were: E. coli (80.8%), K. pneumoniae (13.1%), K. oxytoca (2.3%),
      P. mirabilis (3.1%), P. vulgaris (0.7%). In Smolensk E. coli, K. pneumoniae, P.
      mirabilis were isolated in 96.3, 2.5 and 1.2%, respectively. E. coli occurred in
      100% of Novosibirsk cases. Mean Russian values of the resistance to ampicilline,
      gentamycin, trimetoprim, co-trimoxasol, nitrofurantoin, nalidixic acid,
      pipemidine acid, norfloxacine, ciprofloxacine, nitroxoline were the following:
      33.3, 5.9, 20.3, 18.4, 2.9, 5.5, 4.4, 2.6, 2.6 and 94.1%, respectively.
      Resistance to 2 and more drugs was registered in 18.4% of E. coli strains.
      CONCLUSION: Cystitis in women was in most cases caused by E. coli. The highest
      resistance among uropathogenic strains E. coli was observed to nitroxoline,
      ampicilline, trimetoprim and co-trimoxasole; maximal antibacterial activity
      against uropathogenic E. coli was shown by fluoroquinolones (norfloxacin and
      ciprofloxacin).

PMID- 10900646
TI  - [Lupus nephritis and pregnancy].
AB  - AIM: To evaluate effects of pregnancy on the course and prognosis of lupus
      nephritis and fetal outcome, in particular, in patients with lupus nephritis (LN)
      and antiphospholipid syndrome (APS). MATERIAL AND METHODS: A retrospective
      analysis was made of the course of LN in 31 females (44 pregnancies). RESULTS: A
      favorable outcome of pregnancy is possible in LN women if they had a persistent
      remission at conception. However, one third of these women had exacerbations of
      LN in pregnancy and early postpartum period. Pregnancy developing in active LN
      aggravated LN course in all the women. Fetal outcome was unfavorable. LN was
      especially severe if it arose in the course of pregnancy or early postpartum
      period. It seems that the presence of APS affected pregnancy outcome in a less
      degree than LN activity. CONCLUSION: Both in pregnancy and postpartum period, LN
      showed frequent exacerbations, but if the conception takes place during a
      persistent remission of LN, under adequate care and treatment, a delivery of a
      viable child is possible without an extraordinary risk for the mother.

PMID- 10900647
TI  - [Pregnancy and labor in females with solitary kidney].
AB  - AIM: To propose optimal policy of pregnancy and labor management in females with
      solitary kidney. MATERIAL AND METHODS: The study included 102 pregnant women who
      had contracted or transplanted donor kidney, renal aplasia (17, 3 and 28 females,
      respectively) or had undergone nephrectomy for different diseases (n = 54).
      Filtration, concentration, nitrogen-eliminating renal functions, renal
      hemodynamics, bacteriological picture of the urine were examined. Also,
      ultrasonography of the kidneys, cardiotocographic monitoring, ultrasonic fetal
      biometry, dopplerometry of placental blood flow were made. RESULTS: Most of the
      pregnant women showed declined function of the solitary kidney, but renal
      insufficiency was a rare finding. Pyelonephritis of the solitary kidney, on the
      contrary, occurred rather frequently (77.8%) causing intrauterine infection in
      46% of the fetuses. Obstetric complications arose more frequently than in women
      with two kidneys: gestosis--28%, threatened abortion--18%, premature delivery-
      25%. Hypotrophy was registered in 23% of the newborns. Adequate management of
      pregnancy reduced stillbirth rate to only 5%. 78% of the neonates were born
      mature and had normal body mass. CONCLUSION: Solitary kidney is not
      contraindication to pregnancy while pyelonephritis exacerbation--to abortion.
      Pregnancy is contraindicated in chronic renal failure.

PMID- 10900648
TI  - [Thromboxane A2 and prostacyclin in patients with chronic glomerulonephritis and
      coronary heart disease in contrast media nephrotoxicity. Protective effects of
      calcium antagonists].
AB  - AIM: To study pathological significance of circulating thromboxane A2 and
      prostacyclin in mechanisms of impairment of intrarenal hemodynamics and renal
      function due to contrast media (CM) in risk group patients and to study
      protective effects of calcium antagonists in CM nephrotoxicity. MATERIALS AND
      METHODS: To study plasmic concentrations of TxA2 and prostacyclin, we used
      radioimmunoassay to measure plasmic TxB2 and 6-keto-prostaglandin F1a in patients
      with chronic glomerulonephritis (group 1), systemic atherosclerosis and coronary
      heart disease (group 2). The control group consisted of 23 healthy subjects.
      Diatrizoate (verografin), a high-osmolar CM, was used (40-60 and 250-400 cc in
      groups 1 and 2, respectively). RESULTS: Plasma TxB2 and serum creatinine
      concentrations were significantly elevated in group 1 after CM infusion compared
      to the preinfusion period and healthy controls. Plasma 6-keto-prostaglandin F1a
      in group 1 before CM infusion was lower than in controls after CM infusion. The
      data in group 2 were similar to those for group 1. Administration of nifedipine
      before and after introduction of CM prevented a rise in serum creatinine and had
      beneficial effects on TxA2 and prostacyclin synthesis. CONCLUSION: Ionic CM have
      a renal vasoconstrictive effects mediated by imbalance between vasoconstrictor
      TxA2 and vasodilator prostacyclin and may be nephrotoxic in risk group patients.
      The protective effects of calcium antagonists promote normalization of calcium
      dependent TxA22 and prostacyclin synthesis.

PMID- 10900649
TI  - [Heart remodeling in patients with predialysis phase of chronic renal failure].
AB  - AIM: To investigate remodeling of the heart in patients with predialysis phase of
      chronic renal failure (CRF). MATERIAL AND METHODS: Patients with predialysis
      phase of CRF (n = 61; serum creatinine 412.4 +/- 242.69 mumol/l), essential
      hypertension (EH) (n = 35) and healthy volunteers (n = 20) were assessed with
      echocardiography. The patients were not significantly different by the level of
      systolic and diastolic blood pressure, age and gender. RESULTS: Left ventricular
      mass index (LVMI) was increased in 53(86.9%) patients with CRF. LVMI was not
      different in patients with CRF and EH (189.9 +/- 71.35 vs. 165.0 +/- 41.83 g/m2;
      p = 0.3). Relative wall thickness was similar in patients with serum creatinine <
      200 mumol/l and patients with more elevated serum creatinine (57.2 +/- 10.33 vs
      58.31 +/- 13.33; p = 0.9). The ejection fraction lower than 50% was detected in
      14(22.9%) patients with CRF. Multivariate regression analysis showed that LVMI
      was independently related to systolic blood pressure (p = 0.004) and level of
      hemoglobin (p = 0.004). Diastolic dysfunction (early and atrial peak filling
      velocities ratio < 1.0) was detected in 13(50%) from 26 investigated patients
      with CRF. The independent influence of hemoglobin on isovolumic relaxation time
      (p = 0.04) and early and atrial peak filling velocities ratio (p = 0.02) are
      shown. CONCLUSION: In patients with predialysis phase of CRF left ventricular
      hypertrophy (LVH) is extremely common including patients with mildly elevated
      serum creatinine. The treatment of patients with renal pathology and normal
      function must include measures not only to correct renal process but also to
      prevent development of LVH.

PMID- 10900650
TI  - [Enzyme clearance in intermittent hemofiltration in patients with acute renal
      failure].
AB  - AIM: To characterize elimination of some enzymes in intermittent hemofiltration
      (HF) in patients with acute renal failure (ARF). MATERIAL AND METHODS: 22
      patients with oliguric ARF have undergone 52 procedures of intermittent HF.
      Before the procedure and after it the activity of enzymes (AA, AP, ACE, LAP, GGT,
      GDG, AlAT, AsAT, CPG, LDG) was measured in the samples of plasma and filtrate.
      RESULTS: Besides ACE and AlAT, all the enzymes concentrations were elevated in
      all the patients. HF did not change significantly the enzymes activity. Most of
      the enzymes were eliminated from the blood. In some samples the enzymes activity
      was low or absent. CONCLUSION: Further studies are necessary to answer questions
      aroused by the findings.

PMID- 10900651
TI  - [Risk of chronic renal failure in patients with non-insulin dependent diabetes
      mellitus with diabetic nephropathy and the stage of permanent proteinuria and
      arterial hypertension: role of clinical factors].
AB  - AIM: To reveal prognostic factors which determine the risk of development of
      chronic renal failure (CRF) in patients with diabetes mellitus (DM) type II
      associated with diabetic nephropathy (DN) at the stage of continuous proteinuria
      in combination with arterial hypertension (AH). MATERIAL AND METHODS: A total of
      60 AH patients suffering from type II DM with permanent proteinuria were
      examined. Chronic renal failure was registered in 21 patients. RESULTS: Among CRF
      patients, more frequent were males, high proteinuria and nephrotic syndrome, IHD,
      macroangiopathy of the lower limbs, VLDLP. CONCLUSION: Independent predictors of
      CRF in diabetes mellitus type II with AH and proteinuria were male gender,
      overweight, faster development of stable proteinuria from the time of diabetes
      diagnosis.

PMID- 10900652
TI  - [Continuous ambulatory peritoneal dialysis in patients with diabetes mellitus].
AB  - AIM: To analyse the results of continuous ambulatory peritoneal dialysis (CAPD)
      in diabetes mellitus (DM) patients, to specify complications, to evaluate
      transport characteristics of peritoneal membrane. MATERIAL AND METHODS: The
      ability of peritoneal membrane to eliminate low-molecular substances (creatinine,
      urea), electrolytes and to evaluate treatment efficacy by residual renal function
      (peritoneal equilibration, total urine and creatinine clearance). RESULTS: DM
      patients on CAPD developed vascular complications typical for DM:gangrene (n =
      2), diabetic foot (n = 4), acute disorder of cerebral circulation (n = 3), acute
      myocardial infarction (n = 3). Diabetics' residual renal function deteriorated
      faster than in patients with non-diabetic uremia, though transport
      characteristics of the peritoneum in diabetics and non-diabetics were the same.
      Peritonitis in diabetics was observed much less frequently than in non-diabetics.
      CONCLUSION: CAPD is an adequate replacement therapy in patients with uremia of
      different origin including diabetes. In the course of the treatment DM patients
      develop complications typical for basic disease but their frequency is unrelated
      to CAPD.

PMID- 10900653
TI  - [Erythropoietin drugs in patients with chronic renal failure at the stage of
      conservative treatment. Effectiveness and side effects].
AB  - AIM: To assess activity and safety of erythropoietin (EP) drugs in conservative
      chronic renal failure (CRF). MATERIAL AND METHODS: The antianemic effect of EP
      drugs, central and cardiac hemodynamics were studied in 28 CRF patients (mean
      blood creatinine 5.27 mg%) with renal anemia. In addition, arterial pressure was
      automatically measured within 24 hours and the CRF progression rate was assessed.
      RESULTS: Low-dose EP drugs injected subcutaneously rapidly produced antianemic
      and cardioprotective effects and may improve residual renal function. CONCLUSION:
      Pathogenetically grounded and safe for patients with conservative CRF is a
      combination of low-dose subcutaneous EP drugs with hypotensive drugs (calcium
      antagonists, ACE inhibitors), loop diuretics and low-protein diet.

PMID- 10900654
TI  - [Glucocorticosteroids in bacterial endocarditis: is it beneficial or harmful?].
AB  - AIM: Analysis of results of treatment of infectious endocarditis (IE) with
      glucocorticosteroids in combination with antibiotics. MATERIAL AND METHODS: 128
      IE patients received antibiotics (control group). Glucocorticosteroids were added
      to antibiotics in 44 IE patients (study group). RESULTS: Valvular replacement,
      congestive heart insufficiency, thromboembolic complications, suppression of
      cellular and humoral immunity occurred more frequently in patients of the study
      group. CONCLUSION: It was found that glucocorticosteroids affect IE negatively,
      especially in the dose 30 mg/day and higher. Glucocorticosteroids are indicated
      in allergic reactions to the antibacterial drugs, severe renal damage
      (proteinuria < 1 g/l), myocardial defects; contraindicated in non-eradicated IE
      causative agent, in recurrent IE.

PMID- 10900655
TI  - [Case of effective hemodiafiltration in combined treatment of myocardial
      infarction complicated by acute renal insufficiency].

PMID- 10900656
TI  - [Transitory proteinuria as a symptom of myeloma].

PMID- 10900657
TI  - [Is it safe for cardiological patients to take sildenafil (viagra) to correct
      erectile dysfunction? (lectures)].

PMID- 10900658
TI  - [Renal affection in primary biliary cirrhosis].

PMID- 10900659
TI  - [Renal vein thrombosis in membranous nephropathy (case report and review of
      literature)].

PMID- 10900660
TI  - [Angiotensin II receptor blockers - pilot experience and nephrology
      perspectives].

PMID- 10900661
TI  - [Positive psychology of aging?].

PMID- 10900662
TI  - [Anti-Alzheimer drugs: ethical aspects of research and practice].
AB  - The development and use of drugs that aim at positively influencing the cognitive
      decline in patients suffering from Alzheimer's disease raises a number of ethical
      questions. These concern, amongst others, the significance of these drugs for the
      well-being and quality of life of patients, as well as the informed consent for
      the use of these medicines, in particular in the context of medical-scientific
      research. Assessing the value and significance of antidementia drugs not only
      depends on the positive effect on cognitive decline, but also on the broader
      meaning for the quality of life of the patient and her primary carer(s). The
      subjective experiences of those directly involved deserve more attention in
      research.

PMID- 10900663
TI  - [Elderly and humor: a review].
AB  - Ageing can be associated with physical, cognitive and/or social loss. Most older
      people, however, cope well with this loss, perhaps by using humour. In this
      review the research findings concerning humour were collected. Twenty six
      relevant publications were found. The sense of humour does not seem to be greater
      in older than in younger adults. There are no indications that humour
      appreciation or production is associated with longevity. In older people there is
      a correlation between humour on the one hand and well-being and morale on the
      other. It has not been proven, however, that the use of humour by the elderly
      people has a favourable influence on their health. In health care for older
      people humour is sometimes used as a therapy. Scientific evidence of any positive
      effects of humour on mental health was not found. It is perhaps better for
      caretakers to show appreciation for the humour of older people than to make jokes
      about older people oneself.

PMID- 10900664
TI  - [Patients with Korsakoff's syndrome in a nursing home: characteristics and
      comorbidity].
AB  - This article presents characteristics and co-morbidity of patients with
      Korsakoff's syndrome after admission to a nursing home. The medical charts were
      studied of all patients with Korsakoff's syndrome, admitted between 1984 and 1998
      to the special ward for Korsakoff patients of a nursing home in the eastern part
      of the Netherlands. The 'Standard of classification for diseases in nursing
      homes' ('Standaard van classificatie voor ziekten in de verpleeghuisgeneeskunde')
      was used to classify co-morbidity. The group included 77 patients. Almost 75%
      were male. The average age was 53 years on admission. More than 50% of the
      patients were divorced. After admission, 30% of the group was transferred to a
      different setting. The estimated average follow-up period was 7.1 year. Patients
      had 2.9 co-morbid conditions at admission. Diseases due to alcoholism were
      frequently diagnosed. During the stay skin diseases, psychological disorders and
      behavioural disorders were frequently noticed. The prevalence of cognitive
      impairment and alcohol dementia was surprisingly high. Thirteen patients died,
      most of them of cancer or combined cardiovascular and respiratory diseases. We
      conclude that patients with Korsakoff's syndrome are an unexplored area in
      nursing homes. This group of nursing home inhabitants shows its own
      characteristics and co-morbidity.

PMID- 10900665
TI  - [Undertreatment of hypertension and the risk of stroke in the oldest old].
AB  - The benefit of pharmacological treatment of hypertension in the prevention of
      cardiovascular diseases has been established mainly in subjects younger than 80
      years of age. The consequences of undertreatment of hypertension with regard to
      the occurrence of stroke was studied in the Netherlands. About 33% of the
      hypertensives younger than 80 years and 55% of the hypertensives older than 80
      years were not pharmacologically treated, although they were 'candidates' for
      pharmacological treatment of hypertension. About 19% (n = 1350) of all strokes
      that occurred in the Netherlands in 1994 among hypertensives younger than 80
      years may be attributable to untreated hypertension. Among hypertensives older
      than 80 years this percentage was 32% (n = 1345). Although the benefit of
      pharmacological treatment of hypertension in persons older than 80 years has not
      been established experimentally, the results suggest that a considerable
      proportion of the strokes among this group of hypertensives may be prevented.

PMID- 10900666
TI  - [Insulin resistance and metabolic syndrome].
AB  - The metabolic syndrome represents a complex combination of the symptoms obesity,
      insulin resistance, dyslipoproteinemia, hypertension, and type 2 diabetes. These
      components have a heterogeneous genetic basis and appear to be closely linked.
      Obesity is determined by a polygenic constellation and produces insulin
      resistance, hypertension and dyslipidemia. In addition, defects in the signal
      transduction of insulin appear to aggravate the insulin resistance independent of
      obesity. Type 2 diabetes is produced by a third genetic predisposition and is
      precipitated by the failure of pancreatic beta-cell to compensate insulin
      resistance. Because prevalence and course of the diabetes markedly depend on the
      extent of obesity and insulin resistance, these symptoms of the metabolic
      syndrome represent crucial targets for preventive and therapeutic strategies.

PMID- 10900667
TI  - [10 years of arterial closure devices: a critical analysis of their use after
      PTCA].
AB  - With worldwide over 1 million applications, vascular closure devices have been
      established as an essential tool of invasive cardiology. This overview compares
      today's four commercially available closure devices, VasoSeal (VS), Angio-Seal
      (AS), Perclose, Inc. (PC) and Duett (DU) for their usefulness after coronary
      interventions. The published data regarding deployment success rates for VS, AS,
      PC and DU are in the range of 88%, 91%, 90% and 98% up to 100%, respectively.
      Times to hemostasis were 5-13', 2-4', 11-19' and 4-14', accompanied by times to
      mobilization of 6-9 h, 6-8 h, 4-7 h and 2-6 h. Minor complications were described
      in 8%, 5.9%, 5.3% and 2.1%, major complications in 5.3%, 1.3%, 4% and 2.6%.
      Although none of the closure devices has been shown to reduce major local
      complications as compared to manual compression, all sealing devices have
      documented a significant reduction in time to hemostasis. The increased patient
      comfort is essentially related to the ability of sheath removal immediately after
      PTCA. Vascular closure devices reduce the burden of medical staff and decrease
      hospital costs by earlier discharge.

PMID- 10900668
TI  - [Paclitaxel: a chemotherapeutic agent for prevention of restenosis? Experimental
      studies in vitro and in vivo].
AB  - Paclitaxel, a potent anti-tumor agent, shifts the cytoskeleton equilibrium
      towards assembly of altered and extraordinarily stable microtubules. These
      cellular modifications lead to reduced proliferation, migration, and signal
      transduction. It is highly lipophilic, which promotes a rapid cellular uptake,
      and has a long-lasting effect in the cell due to the structural alteration of the
      cytoskeleton. This makes paclitaxel a promising candidate for local drug delivery
      intended to address the proliferative and migratory processes involved in
      restenosis. In this article, results of our in vitro and in vivo studies with
      paclitaxel are presented. Cell culture experiments with monocultures of human
      arterial smooth muscle cells as well as co-cultures with human endothelial cells
      showed that paclitaxel leads to an almost complete growth inhibition within a
      dose range of 1.0-10.0 mumol/l, even after a short (20 min) single dose
      application. The comparison of an active, semi-active, and passive delivery
      system (porous balloon, microporous balloon, and double balloon) favored the
      double balloon for the following in vivo experiments. Tubulin staining and
      electron microscopy enabled visualization of paclitaxel-induced vessel wall
      alterations. In the rabbit model, locally delivered paclitaxel resulted in
      reduced neointima formation and enlargement in vessel size; in the pig model,
      however, after stenting, this inhibition was not significant. Both reduced
      proliferation and enlargement in vessel size contribute to a preservation of
      vessel shape and are likely to be caused by a structural alteration of the
      cytoskeleton, which is also supported by vascular contraction force experiments.

PMID- 10900669
TI  - [Selective kidney angiography within the scope of heart catheterization:
      pathological findings and therapeutic consequences].
AB  - BACKGROUND: The importance of renal artery stenosis as a cause of refractory
      hypertension, recurrent pulmonary edema and renal failure is being increasingly
      recognized. The prevalence and clinical consequences of renovascular and
      macroscopic renal parenchymal pathology in patients undergoing coronary
      angiography is assessed prospectively. PATIENTS AND METHODS: Selective renal
      artery angiography was performed in 190 consecutive patients following coronary
      angiography and prior to PTCA if indicated. Diagnostic yield, therapeutic
      consequences, complications and fluoroscopy time were noted. RESULTS: Mean age as
      63 (+/- 11) years, 74% of patients were males. Mean fluoroscopy time (including
      PTCA or PTA) was 8 (+/- 11) minutes. The pathological renal and renovascular
      findings included critical atherosclerotic renal artery stenosis in four patients
      (2%), non critical (angiographically < 60%) stenosis in 22 patients (12%), double
      arterial supply on one side in 26 patients (14%), on both sides in seven patients
      (4%), fibromuscular dysplasia in two patients (1%) and large renal cyst, renal
      artery aneurysm and aberrant blood supply of an ectopic pelvic kidney in one
      patient (0.5%). The four patients with critical renal artery stenosis underwent
      primarily successful PTA and stenting. CONCLUSIONS: Selective renal angiography
      in the wake of coronary angiography is safe and inexpensive. Furthermore, it can
      be performed easily in the majority of cases. The diagnostic yield of renal
      angiography ist not negligible; 2% of patients had critical renal artery stenosis
      with an unequivocal indication for an interventional procedure. Progression of
      (as yet) nonsignificant renal artery stenosis is reported in a large number of
      cases, meaning that early diagnosis may have later therapeutic consequences. Ad
      hoc PTA and stenting is the treatment of choice for significant renal artery
      stenosis.

PMID- 10900670
TI  - [Percutaneous reconstruction of a pelvic vascular occlusion using the "kissing
      balloon" technique].
AB  - A 43-year-old patient was admitted for severe claudication in his right leg,
      doppler ultrasound and angiography revealed an occluded right common iliac
      artery. Using the cross-over-approach from the contralateral side, it was
      possible to navigate a guide wire through the occlusion, and after passage with
      an excimer laser an ipsilateral retrograde puncture with placement of a sheath
      was performed. In order to protect the the aortoiliac bifurcation, a primary
      stent implantation of the occluded side was carried out using the kissing balloon
      technique. Afterwards three stents were placed. Subsequently the patient
      completely improved; treadmill exercise test and duplex sonography showed good
      results. CONCLUSION: Using the kissing balloon technique, laser-assisted
      recanalisation of iliac artery occlusions even involving the aortoiliac
      bifurcation compare favorable to other more invasive treatments. A surgical
      procedure can thus be avoided.

PMID- 10900671
TI  - [6 years clinical experience with the TEKNA bivalve heart valve prosthesis].
AB  - OBJECTIVE: The revised Edwards-Duromedics valve was introduced onto the market in
      June 1990. In September 1993, the producer changed the name of the valve to
      TEKNA, which is a low profile, bileaflet, mechanical prosthesis with a self
      irrigating hinge mechanism. The results of a prospective follow-up study after
      valve replacement with this prosthesis are presented. METHODS: From November 1990
      to December 1996, 173 TEKNA prostheses were implanted in 161 patients (73 men, 88
      women), either in the aortic (AVR; 48.4%), mitral (MVR; 44.1%), or aortic and
      mitral positions (DVR; 7.5%). Patient ages ranged from 17 to 83 years (mean age
      59.2 +/- 8.7 years). Follow-up was 97.5% complete, comprising 433.15 patient
      years for a mean follow-up of 34.8 +/- 23 months. RESULTS: Overall operative (30
      day) mortality was 4.97%. Fifteen patients died in the late period, corresponding
      to a linearized late mortality rate of 3.5%/pt-yr. Actuarial survival at six
      years was 75.3% +/- 6.2% overall. The actuarial freedom from complications was
      calculated as follows (linearized rates in parentheses): valve-related mortality
      91.3% +/- 5.1% (0.92%/pt-yr); thromboembolism 94.2% +/- 2.5% (1.62%/pt-yr); valve
      thrombosis 98.6 +/- 1.0% (0.46%/pt-yr); bleeding events 85.9% +/- 4.7% (2.77%/pt
      yr); prosthetic valve endocarditis 98.6 +/- 0.9% (0.46%/pt-yr); nonstructural
      dysfunction 93.2 +/- 3.2% (1.38%/pt-yr); reoperation 87.1 +/- 5.3% (2.08%/pt-yr).
      Functional class according to NYHA was improved from preoperatively 72.05% in III
      or IV to 6-year postoperative 94.2% in I or II. CONCLUSION: The clinical
      performance of the TEKNA valve is quite satisfactory, with low incidence of valve
      related complications. No structural deterioration has been observed. Further,
      the patients physical ability and quality of life were significantly improved.

PMID- 10900672
TI  - [Symptomatic true aneurysm of a venous bypass with compression of the right
      atrium].
AB  - A symptomatic true aneurysm of a saphenous vein graft to the right coronary
      artery in a female patient twelve years after bypass surgery is presented.
      Beating heart surgery included resection of the aneurysmatic saphenous vein
      graft, reconstruction of the right atrium and coronary artery bypass grafting to
      the right coronary artery. The symptoms of aneurysms of vein grafts, the
      diagnostic procedures and the surgical treatment are discussed.

PMID- 10900673
TI  - [Intensified after-care--a method for improving occupational reintegration after
      myocardial infarct and/or bypass operation].
AB  - Occupational reintegration after coronary heart disease of patients who are
      insured by the German workers pension (Arbeiterrentenversicherung) succeeds in 40
      60% of the recorded cases. Patients who were not able to return to work after
      finishing their regular cardiac rehabilitation took part in a program called
      "Intensivierte Nachsorge (INA)". INA is an interdisciplinary support program,
      taking place twice a week for a whole day over a period of six weeks. On the
      remaining three days patients were either progressively reintegrated into their
      working place or stayed at home. The results of the INA group were compared to
      those of a control group. Two years after patients had terminated the cardiac
      rehabilitation, statistically significant effects could still be found: 70.2% of
      the INA group had returned to work compared to 52.6% of the control group. This
      is a difference of 17.6%. After the results had been corrected by considering age
      differences between the two groups, the control group had a recalculated return
      to work rate of 57.4%. A significant difference of 12.8% could still be
      identified with respect to the INA group. Support programs which follow regular
      cardiac rehabilitation seem to be specially suitable for older patients with
      highly perceived job strain, because our results showed that these patients had
      lower return to work rates. 44.2% of the INA group and 21.9% of the control group
      were progressively reintegrated into their work place. Two years after their
      regular rehabilitation 36.3% of the INA group patients took part in ambulatory
      heart groups compared with 10.4% of the control group. It was also found that
      patients of the INA group showed improvements in activities of daily life. The
      INA program however does not seem to have an influence on behavioral components
      such as eating habits, relaxation, and smoking as well as on the psychological
      status. The physical fitness measured in watt x min at the beginning of the INA
      program (T1) was 589.46 +/- 255.03 in the control group. This number increased to
      598.32 +/- 276.01 six months after regular rehabilitation (T3) and continued to
      rise to 661.15 +/- 362.01 after two years (T4). In the INA group the numbers were
      as follows: 658.13 +/- 263.63 at T1, 751.83 +/- 318.15 at T3, and 717.93 +/-
      336.76 at T4. The differences between the groups are significant at T1 and T3,
      whereas at T4 there is no significant difference. It should also be stated that
      the lipid parameters indicated no differences between the groups except for the
      triglyceride values which were significantly lower statistically in the INA group
      than in the control group.

PMID- 10900674
TI  - [Anti-ischemia effect of estrogens].
AB  - Consideration of estrogen replacement therapy is well established in the
      treatment of postmenopausal syndrome and osteoporosis in menopause. Some
      observational epidemiologic studies on this topic have suggested beneficial
      effects on cardiovascular disease. A prospective, controlled, randomized clinical
      trial with respect to cardiovascular events and mortality in postmenopausal
      hormone users, the HERS (Heart and Estrogen/Progestin Replacement) study has
      recently been published. Anti-ischemic effects of estrogens are mediated by
      improvement of menopausal-associated endothelial dysfunction, calcium antagonism,
      and activation of endothelial synthesis of prostacyclin. Improvement in
      functional state and reduction of stress-induced myocardial ischemia with hormone
      replacement therapy (HRT) have been demonstrated in several clinical trials.
      Thus, because of available clinical data, introduction of HRT for cardiovascular
      reasons in patients with coronary artery disease is still considered ambiguous
      and cannot be generally recommended for secondary prevention in this group of
      patients.

PMID- 10900675
TI  - [The effects of estrogen in the cardiovascular system].
AB  - Estrogen replacement therapy (ERT) has been established for the treatment of
      perimenopausal symptoms and postmenopausal prevention of osteoporosis. Clinical
      (not randomized) cohort studies have shown an association of a significantly
      reduced cardiovascular mortality with ERT. However, a first randomized, double
      blind and placebo-controlled study (HERS) could not support these findings.
      However, this study is limited by the use of (heterogeneous) conjugated estrogens
      and combined progestin treatment because animal experiments demonstrated an
      inhibition of protective estrogen effects by progesterone. On the other hand,
      experimental and clinical findings demonstrated beneficial estrogen effects on
      lipid metabolism, lipid-peroxidation, smooth-muscle-cell proliferation,
      hemostasis, and vasomotion. Actually, several authors are discussing the
      mediation of estrogen's effects by vascular estrogen receptors. Recent findings
      on different subtypes of estrogen receptors (ER-alpha and ER-beta) may explain
      some antagonistic effects as proliferation in the one (endometrium) and anti
      proliferation in the other (vascular wall) tissue. In this context, the exact
      detection of the mechanism(s) of estrogen action may probably lead to new
      approaches in the treatment of coronary artery disease.

PMID- 10900676
TI  - [Nutrient intake with low-fat diets in rehabilitation of patients with coronary
      heart disease].
AB  - We investigated the nutritional value of a very low fat diet (diet I) adapted to
      nutritional habits in Germany. Data were compared to a low fat diet (diet II)
      according to the American Heart Association. The study was performed in 37
      patients with coronary heart disease (30 males and 7 females, age 45-83 yrs)
      stratified to the 2 dietary treatments. Daily fat intake was 38 g (24% of energy
      intake of 6.5 MJ/d) in diet I and 60 g (31% of 7.3 MJ/d) in diet II (p < 0.01),
      respectively. When compared with diet II, in diet I the intake of cholesterol,
      saturated and mono-unsaturated fatty acids, Vit. A, Vit. D and Vit. B12 were all
      reduced (p < 0.01), whereas the uptake of Vit. C was increased p < 0.01. The
      intake of folic acid was low in both groups. Both diets resulted in a decrease in
      BMI, systolic and diastolic blood pressure, plasma cholesterol and LDL
      cholesterol levels. Concomitantly plasma triglycerides only decreased in response
      to diet I but HDL cholesterol levels remained unchanged. Reduction of BMI and
      cholesterol levels were dependent on baseline BMI and cholesterol concentrations,
      respectively. The cholesterol lowering effect of diet I is in part attributed to
      the weight lowering effect of the diet. Taking into account the nutritional
      habits in Germany, very low fat diets seem to be adequate with respect to their
      nutritional value. Both diets are effective in lowering body weight, plasma
      cholesterol and triglyceride levels without affecting HDL cholesterol. These
      effects are most pronounced in overweight and hypercholesterolemic patients.

PMID- 10900677
TI  - [A case report: suppurative pericardial effusion].
AB  - We present the case of a 67 year old woman who was resuscitated due to cardiac
      tamponade. Examination of the pus fluid showed a bacterial infection with
      streptococcus milleri. Four days before resuscitation the patient experienced
      weakness, dyspnoea, increased temperature (39 degrees C), swelling of the neck,
      and pain on swallowing. Using computed tomography, examination revealed an
      infection extending from the right tonsil to the mediastinum and into the
      pericardium. After surgery to remove the retropharyngeal abscess, the patient
      healed well. Therefore, on presentation of a cardiac tamponade, possible
      hematogenous or lymphogenous causes or per continuitatem infections should always
      be considered. In this case the germs in the fluid and the typical patient
      history indicated an oropharyngeal reason.

PMID- 10900678
TI  - ["Right is there, where the thumb is left,"].

PMID- 10900679
TI  - [A case of sarcomatosis of the spinal cord. 1903 classical article].

PMID- 10900680
TI  - [Psychopathological phenomena and personality disorders (the issue of dynamic
      aspects of psychopathologies)].
AB  - An analysis of the interaction between pathocharacterological and
      psychopathological (affective, anxious-phobic and hysterical) phenomena within
      "borderline psychiatry" (reactions, phases, development) gives evidence to the
      existence of 2 clinically heterogeneous variations of comorbid interactions. The
      first variation: primary psychopathological syndromes manifesting without any
      significant correlation with personality disorders and transform into
      pathocharacterological ones (neurotic, postreactive) personality development by
      means of "amalgamating" mechanism. The second variation: secondary (in regard to
      personality disorders) psychopathological phenomena forming on the basis of
      constitutional personality traits by means of "splitting off" mechanism and are
      defined as personality disorders with predisposition to manifest positive
      psychopathological symptomatology. Formation of isolated obsessive and
      dissociative disorders within the structure of "basic" pathocharacterological
      phenomena (variation 2) predicts a future absence of growing severity of
      personality disorders (i.e. a dynamics traditionally defined as the development-
      variation 1) and stabilization of psychopathic traits with features of
      compensation of the latter. The possibilities of pathological dynamics in
      psychopathic personality with a "splitting off" of the isolated
      psychopathological syndromes exhausted; for decades neither growing severity of
      personality disorders, nor an exacerbation of those psychopathological complexes
      which provided a primary base for manifestation of positive symptomatology may be
      observed.

PMID- 10900681
TI  - [Dynamics of functional state of the post-stroke patients].
AB  - A dynamics of the functional state was analyzed in 197 patients aged 34-80 years
      after the stroke that had happened from several weeks to 17 years ago. The
      patients were included into the stroke patients computer data bank established in
      Bekhterev's Institute. It was proved possible to use the "PULSES" profile and
      "Rehabilitation Level" test for objective assessment of both clinical-social
      outcomes and efficiency of the treatment of patients with consequences of
      cerebral stroke. There was no any direct correlation between the dynamics of
      neurological syndrome, on the one hand, and functional state of the patient, his
      social-working adaptation, on the other hand. It is suggested that both
      psychophysiologic and social adaptation raise functional potential of patients
      with consequences of cerebral stroke.

PMID- 10900682
TI  - [Clinico-psychopathological characteristics of states in patients with suicidal
      attempts].
AB  - A total psychiatric examination of the persons, after attempted suicides was
      performed during a month of stay in the department of resuscitation of the N.V.
      Sklifosovsky Institute for the Emergency Medical care. In all the patients some
      mental pathology was found that took place in the moment of suicide and long
      before it. In most of the cases the disorders of either affective (48.7%) or
      schizophrenic (38.5%) spectrum were diagnosed. Psychogenic reactions to stress
      and personality disorders were in only 10.2% of the patients. In most of the
      patients (74.7%) a mental disease wasn't diagnosed before in spite of its long
      duration (11.5 years on the average).

PMID- 10900683
TI  - [Neurological masks of depression (effectiveness of tianeptine)].
AB  - 40 patients with panic attacks, chronic algesic syndromes (chronic headaches of
      tension, cardialgias) entered the study. They also had depression of mild or
      moderate degree. 65% of the patients denied actively disorders of the mood; 80%
      were sure that they had a severe disease that was difficult to diagnose; most of
      them doubted the efficiency of therapy with psychotropic preparations. An
      analysis of the polymorphism of clinical symptomatology of the masked depression
      revealed in more than half of the patients some combinations of clinical
      syndromes, such as autonomic dysfunction, algesic manifestations, motivation and
      insomniac disorders. A structure of panic attacks was characterized by the
      prevalence of the autonomic symptoms as compared with the anxious ones. All the
      patients were treated with tianeptine (37.5 mg/day) during six weeks. The therapy
      was effective in 67.5% of the patients. The study revealed an equal efficiency of
      the drug in comorbid depressive, anxious and autonomic disorders as well as a
      good tolerance.

PMID- 10900684
TI  - [The use of midokalm in patients with multiple sclerosis].

PMID- 10900685
TI  - [Certain biochemical blood markers in the process of cholinergic therapy in
      Alzheimer's disease].
AB  - Acetylcholinesterase (AChE) activity and parameters of the system of regulation
      of lipid peroxidation (LPO) were estimated in blood of patients with Alzheimer's
      disease (AD) during therapy with amiridine and gliatiline. It was found that the
      therapy was accompanied by inhibition of AChE activity. A significant correlation
      was observed between clinical efficiency and changes of AChE activity. AD was
      characterised by essential changes in LPO parameters: the level of the primary
      products of oxidation was increased three times with a sharp increase (seven
      times) of total unsaturation of lipids. A significant correlation was found
      between AChE activity and the level of the primary products of oxidation in blood
      erythrocytes of AD patients before and after therapy with amiridine and
      gliatiline.

PMID- 10900686
TI  - ["Fast" and "slow" components of psychotropic activity of the drugs with
      nootropic effects].
AB  - A clinical-pharmacological study was carried out to evaluate correlation of
      "fast" (nonspecific) and "slow" (specific) components of the action of the drugs
      with nootropic properties (piracetam, mexidol, tanacan) and to estimate their
      contribution to achieving therapeutic efficacy. The study was performed during 28
      days using standard quantitative assay techniques in 79 patients with "Organic
      emotional-liable (asthenic) disorders" (F06.6, ICD-10). It was found that "fast"
      component of the psychotropic action of the drugs tested was presented by
      stimulating and anxiolytic effects, while a "slow" one--by specific nootropic
      activity. All these effects were fully independent with no correlation found, and
      this could, probably, be attributed to different mechanisms of their realization.
      It is shown that nootropic activity of piracetam was most significant in its
      therapeutic effect; and anxiolytic effect was most important for mexidol action.
      Meanwhile, stimulating and anxiolytic activities as well as positive influence on
      long-term memory were main components of tanacan effect. The results obtained
      show an important role of both specific and nonspecific ("fast") effects in
      realization of therapeutic action of the drugs with nootropic effects in patients
      with cognitive-mnestic and neurosis-like disorders.

PMID- 10900687
TI  - [Semiquantitative evaluation of autoregulation of cerebral blood supply in norm].
AB  - Elaboration of an informative, noninvasive method for evaluation of the reserve
      of the cerebral circulation is an urgent problem of angioneurology. The authors
      propose a method of dopplerographic estimation of the autogerulatory response by
      hyperthermic changes after short-term period of regional hypotension induced by
      digital compression of carotid artery on the neck. The indices acceptable in
      daily clinical practice were calculated. There was determined a range of their
      values at normal tonus of the resistive vessels, on the background of hypo- and
      hypertension induced by hypercapnic and hypocapnic loads, respectively. Test of
      carotid compression with registration of the linear velocity of blood flow in
      cerebral arteries is safe, significant and reproducible way for a
      semiquantitative estimation of the reserve of autoregulation. It may be used for
      evaluation of tonus of resistant vessels of the reservoir of the middle carotid
      artery as one of the most important index of the functional state of the system
      of cerebral circulation.

PMID- 10900688
TI  - [New approaches to the evaluation of functional state of afferent central nervous
      system pathways in patients with syringomyelia].
AB  - Functional state of both afferent and efferent pathways of CNS was studied with
      the method of magnetic stimulation (MS) in patients with syringomyelia. A control
      group contained 35 healthy individuals. The state of the efferent pathways was
      estimated by the time of the central motor conduction. The state of the afferent
      pathways of brain stem and spinal cord was analyzed by the latency of the motor
      responses of the orbicular muscle of the eye to MS of the spinal cord on the
      level of cervical and lumbar regions. The signs of the disorders in the
      conduction of the excitement through pyramidal pathways as well as through the
      afferent pathways of the spinal cord and the brain stem were registered in
      patients with syringomyelia. This observation allows to increase considerably the
      diagnostic range of MS.

PMID- 10900689
TI  - [The status of cerebral hemodynamics in patients with vertebro-basilar
      insufficiency syndrome].
AB  - The state of venous and arterial cerebral hemodynamics was studied using
      ultrasonic dopplerography with application of hypo- and hypercapnia,
      angioencephaloscintigraphy with pertecnetate Tc-99m in 48 patients with syndrome
      of vertebrobasilar insufficiency. Estimation was performed in patients by the
      results of neurological and otoneurologic evidence, the data of nistagmography
      and registration of the truncal evoked potentials. It was found that at early
      stages of the development of vertebrobasilar insufficiency's syndrome disorders
      of vasomotor reactivity and disturbances in venous hemodynamics play a leading
      role in its pathogenesis. Stenosis damages of extra- and intracranial arteries
      become dominating in subsequent clinical picture.

PMID- 10900690
TI  - [Comparative clinico-immuno-chemical analysis of remittent and secondary
      progressive course of multiple sclerosis].
AB  - Immunochemical monitoring of remittent and secondary-progressive course of
      multiple sclerosis (MS) was performed. Examination of 61 patients was performed
      during 3 years. Inflammatory cytokines: (IL-1, IL-2, IL-6, TNF-alpha), were
      measured in supernatants of the peripheral blood mononuclear cells while some
      neurospecific proteins (GFAP and alpha 2-GP), vesicular-cellular molecules of the
      adhesion (sVCAM-1) were estimated in blood serum. 50 healthy donors entered the
      control group. The results demonstrated a remaining functional tension of cell
      immunity and a decrease of the resistance of hematoencephalic barrier (HEB) at
      all MS stages. However, in secondary-progressive MS concentration of the sVCAM-1
      in blood serum was elevated as compared with the control group, patients with
      remittent course and in clinical improvement. It is suggested that some
      functional alteration of HEB endothelium, manifest in constant pathologic
      expression of sVCAM-1 molecule, is one of the pathochemical mechanisms promoting
      progression of MS process.

PMID- 10900691
TI  - [Neuritis of the facial nerve and its connection with herpes viruses].

PMID- 10900692
TI  - [Clinico-pathogenetic evaluation of the headache syndrome in cerebral stroke].

PMID- 10900693
TI  - [The levels of the neuro-mediating amino acids in the blood of patients with
      alcoholic delirium].

PMID- 10900694
TI  - [Multiple visceral lesions of internal organs in opioid dependency].

PMID- 10900695
TI  - [Alexithymia].

PMID- 10900696
TI  - Asthma and respiratory symptoms among school children in United Arab Emirates.
AB  - OBJECTIVES: To determine the prevalence of asthma, wheezing, hay fever, and
      eczema among primary school children aged 6-13 years in United Arab Emirates
      (UAE). DESIGN: A cross-sectional study on school children was performed using the
      International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires.
      SETTING: Government primary school children in seven Emirates, in UAE. SUBJECTS:
      Subjects were selected by a multi-stage stratified sampling design. 4200 children
      targeted for this study, but only 3200 children aged 6-13 years were agreed to
      participate and responded to the study. The overall response rate was 69.8%.
      RESULTS: The prevalence of physician diagnosed asthma was 13%, in addition, the
      wheeze by history was 15.6%. Furthermore, the prevalence of nocturnal cough was
      21%. On the other hand, the prevalence of eczema was 11% and hay fever was 14.9%.
      Parental asthma but not parental atopy was associated with an increased risk of
      asthma and wheezing in children. CONCLUSIONS: The prevalence of asthma and
      wheezing in UAE is consistent with that in neighbouring Gulf countries.

PMID- 10900697
TI  - Effects of time-pressure on decision-making under uncertainty: changes in
      affective state and information processing strategy.
AB  - An experiment is reported that investigated the extent to which affective state,
      information processing strategy and task structure determine the effects of time
      pressure on decision-making. Research participants were presented with risk
      scenarios involving a choice between safe and risky actions. The scenarios were
      systematically varied in terms of outcome valence (positive or negative) and
      effort associated with taking the safe action (high or low). Half the
      participants were given unlimited time to make their decision, the other half
      were required to choose within a deadline. The findings showed that time
      pressured participants were more anxious and energetic and used a number of
      different strategies to cope with the deadline. These effects, as well as changes
      in risk-taking, were shown to vary systematically with task structure,
      particularly the effort manipulation. The findings are discussed in terms of how
      they contribute to theories of time-pressure and the methodological implications
      they have for future research in this area.

PMID- 10900698
TI  - Attributions of responsibility and affective reactions to decision outcomes.
AB  - Immediate affective reactions to outcomes are more intense following decisions to
      act than following decisions not to act. This finding holds for both positive and
      negative outcomes. We relate this "actor-effect" to attribution theory and argue
      that decision makers are seen as more responsible for outcomes when these are the
      result of a decision to act as compared to a decision not to act. Experiment 1 (N
      = 80) tests the main assumption underlying our reasoning and shows that affective
      reactions to decision outcomes are indeed more intense when the decision maker is
      seen as more responsible. Experiment 2 (N = 40) tests whether the actor effect
      can be predicted on the basis of differential attributions following action and
      inaction. Participants read vignettes in which active and passive actors obtained
      a positive or negative outcome. Action resulted in more intense affect than
      inaction, and positive outcomes resulted in more intense affect than negative
      outcomes. Experiment 2 further shows that responsibility attributions and
      affective reactions to outcomes are highly correlated; that is, more extreme
      affective reactions are associated with more internal attributions. We discuss
      the implications for research on post-decisional reactions.

PMID- 10900699
TI  - Action tendencies and characteristics of environmental risks.
AB  - It is assumed that the mental representation of the causal structure of
      environmental risks, i.e., the type of cause and the type of potential
      consequence, determines which sort of action tendencies are formed. We propose a
      model of risk evaluation that includes consequentialist and deontological
      judgments as well as specific emotions as mediators of action tendencies. Four
      hundred participants took part in an experiment which presented scenario
      information about environmental risks. The scenarios differed with respect to (a)
      causation (human vs. natural cause; single vs. aggregate causation), (b)
      consequence (harm to self vs. harm to other people vs. harm to nature), and (c)
      geographical distance (proximate vs. distant). Participants indicated how much
      they preferred each of 31 prospective behaviors. Factor analyses yielded five
      types of action tendencies: help, aggression, escape, political action, and self
      focus. The causal structure of the risks was systematically related to action
      tendencies, e.g., environmental risks that are caused by humans, and in
      particular those caused by a single human agent, elicit aggressive action
      tendencies. The findings conform that the perceived causal structure of a
      specific risk determines whether the focus is upon consequentialist or
      deontological judgments, which, in turn, elicit specific types of action
      tendency, mediated by emotions.

PMID- 10900700
TI  - Models of risk and choice: challenge or danger.
AB  - A dimensional model of perceived risk and a model of risk acceptance based on
      risk rates are proposed in this paper. In line with the proposed model of
      perceived risk, risk is a linear combination of the three basic dimensions of a
      risky situation: the amount and probability of loss and the amount of gain. It is
      assumed that psychological transformations are made on these dimensions.
      According to the model of acceptance, acceptance is judged by making a trade-off
      between perceived risk and the amount of gain. These models have been
      investigated in two experiments, in which risk judgments and acceptance rates for
      a set of descriptions of risky investments were collected from managers in
      Poland. The proposed dimensional model of perceived risk was compared to the
      distributional models of risk and to the risk models based on the expectation
      principle. The best fit was obtained for the proposed model. It was also found
      that perceived risk was useful in predicting acceptance rates. Better fits were
      obtained for the models of acceptance, based on perceived risk, than for the
      expected/weighted utility models, including bilinear models.

PMID- 10900702
TI  - Taking advice, using information and knowing what you are doing.
AB  - Subjective descriptions of judgment policies have been found to be imperfect.
      This could be because subjective weights are obtained on just a single occasion
      after all judgments have been completed. It could also be because people have
      tended to state their perception of an ideal way of responding rather than their
      perception of how they actually responded. Finally, it could be because they
      experience difficulty in relating variation in stimulus dimensions to variation
      in quite different response dimensions. In our task, people made sales forecasts
      on the basis of four pieces of information. They also stated the weight they
      placed on each one and the weight they should have placed on it. The means of
      weights stated on each trial were more appropriate than those stated at the end
      of all trials. Stated actual weights were very similar to stated ideal weights.
      Weights were more appropriate when forecasts and cues varied along the same
      dimension than when they did not. Thus, our results are consistent with the view
      that all three factors affect people's ability to provide subjective descriptions
      of their judgment policies.

PMID- 10900701
TI  - Confidence in aggregation of expert opinions.
AB  - We investigate the case of a single decision maker (DM) who obtains probabilistic
      forecasts regarding the occurrence of a unique target event from J distinct,
      symmetric, and equally diagnostic expert advisors (judges). The paper begins with
      a mathematical model of DM's aggregation process of expert opinions, in which
      confidence in the final aggregate is shown to be inversely related to its
      perceived variance. As such, confidence is expected to vary as a function of
      factors such as the number of experts, the total number of cues, the fraction of
      cues available to each expert, the level of inter-expert overlap in information,
      and the range of experts' opinions. In the second part of the paper, we present
      results from two experiments that support the main (ordinal) predictions of the
      model.

PMID- 10900703
TI  - Effects of the beholder's age on the perception of facial attractiveness.
AB  - Children have been shown to prefer faces rated as highly attractive by adults
      over faces rated as quite unattractive. We investigated to what extent this
      agreement holds not only for the general direction of preferences but for
      preference strengths as well. In a choice experiment, we presented 40 nine-year
      old girls and their mothers and 40 twelve-year-old girls and their mothers with
      pairs of women's and girls' faces and asked the subjects to pick the face that
      appeared prettier to them. Preference frequencies and simple attractiveness
      scales derived from these preference frequencies by fitting the Bradley-Terry
      Luce rule (Luce, D. R. (1959). Individual choice behavior: a theoretical
      analysis. New York: Wiley) were compared across subject groups. For the women's
      faces, we found no difference in preferences between nine-year-olds, twelve-year
      olds, and adults, neither in direction nor in strength. For the girls' faces, we
      also found no major differences in preference direction, however, we did find
      reliable differences in preference strengths. To a considerable part these
      differences were due to the fact that the children showed less pronounced
      preferences between face stimuli than the adults. These results suggest a role of
      developmental factors in the perception of facial attractiveness.

PMID- 10900704
TI  - Mean response times, variability, and skew in the responding of ADHD children: a
      response time distributional approach.
AB  - Response time (RT) distributions from three fixed foreperiod conditions (2, 4,
      and 8 s) in a warned four-choice RT task were obtained for a group of boys with
      attention-deficit/hyperactivity disorder, combined type (ADHD; n = 17) and for
      two groups of normal control boys (age-matched, n = 18, and younger-aged, n =
      10). Quantitative measures of distributional shape were derived by fitting the ex
      Gaussian distributional model to the individual RT data. Statistical results
      indicate that the ADHD distributions differ from the age-matched control
      distributions with respect to the size of the tail (larger for the ADHD boys),
      but differ from the younger control distributions with respect to the location of
      the leading edge (slower for the younger control boys). Receiver operating
      characteristic (ROC) results reveal that the ex-Gaussian exponential component is
      highly diagnostic of the ADHD boys.

PMID- 10900705
TI  - The influence of semantic context on initial eye landing sites in words.
AB  - To determine the role of ongoing processing on eye guidance in reading, two
      studies examined the effects of semantic context on the eyes' initial landing
      position in words of different levels of processing difficulty. Results from both
      studies clearly indicate a shift of the initial fixation location towards the end
      of the words for words that can be predicted from a prior semantic context.
      However, shifts occur only in high-frequency words and with prior fixations close
      to the beginning of the target word. These results suggest that ongoing
      perceptual and linguistic processes can affect the decision of where to send the
      eyes next in reading. They are explained in terms of the easiness of processing
      associated with the target words when located in parafoveal vision. It is
      concluded that two critical factors might help observing effects of linguistic
      variables on initial landing sites, namely, the frequency of the target word and
      the position where the eyes are launched from as regards to the beginning of the
      target word. Results also provide evidence for an early locus of semantic context
      effects in reading.

PMID- 10900706
TI  - Age-of-acquisition effects in semantic processing tasks.
AB  - In two experiments, we examined whether word age-of-acquisition (AoA) is a
      reliable predictor of processing times in semantic tasks. In the first task,
      participants were asked to say the first associate that came to mind when they
      saw a stimulus word; the second task involved a semantic categorisation between
      words with a definable meaning and first names. In both tasks, there were
      significantly faster responses to earlier-acquired than to later-acquired words.
      On the basis of these results, we argue that age-of-acquisition effects do not
      originate solely from the speech output system, but from the semantic system as
      well.

PMID- 10900707
TI  - Wisconsin Card Sorting in adolescents: analysis of performance, response times
      and heart rate.
AB  - Forty-nine adolescents performed the Wisconsin Card Sorting Test (WCST). A main
      PCA component of WCST performance was identified as 'efficiency of reasoning'.
      This factor was related to feedback processing. From the WCST, a perseveration
      score can be derived. Perseveration is the continued application of a rule, after
      it has been disconfirmed. We compared more and less perseverating subjects in
      relation to stimulus-response (SR) time, feedback inspection time and cardiac
      acceleration and deceleration. Less perseverating subjects responded faster, and
      had longer and more adaptive inspection times of error feedback. We examined the
      switch from rule application to rule search, and the difference between correct
      and error responses. A transient cardiac deceleration at the initiation of rule
      search was interpreted as a change in supervisory attention. An error-related
      deceleration to negative feedback was interpreted as a disturbance of higher
      control processing. Previous trial feedback influenced current processing time,
      feedback inspection time, and the cardiac acceleration and deceleration
      responses.

PMID- 10900708
TI  - The interaction of observational learning with overt practice: effects on motor
      skill learning.
AB  - This study explored various methods of combining observational learning via
      demonstration with the effects of overt practice for learning a discrete action
      pattern. Three groups were compared that varied by the timing of demonstration in
      relation to practice. An all-pre-practice demonstration group viewed 10 pre
      practice videotape demonstrations of an expert performing the skill, and then
      engaged in practice. An interspersed demonstration group viewed one pre-practice
      demonstration, then initiated practice on the skill. Every three attempts,
      practice was halted while participants viewed another demonstration, with this
      pattern repeated throughout acquisition. A combination demonstration group
      experienced elements of each schedule by viewing five demonstrations prior to
      practice, then five more once practice had begun (one every three attempts) so
      that modeling was completed by mid-acquisition. Ratings of form and accuracy were
      assessed in an acquisition phase, an immediate retention test, and a 48-h
      retention test. Group main effects for form scores were detected in acquisition,
      immediate, and 48-h retention, with the combination group obtaining the highest
      form scores, followed by the all-pre-practice group, and finally the interspersed
      group. These findings suggest that several modeling exposures before practice and
      several more exposures in the early stages of practice were optimal for
      acquisition and retention of form.

PMID- 10900710
TI  - [The current objective criteria for the adequacy of general anesthesia in
      children].
AB  - Auditory evoked potentials (AEP) were recorded and analyzed in 12 children during
      general halothane and ketamine anesthesia. Ketamine suppressed the amplitude of
      primary negative component and eliminated secondary AEP components with latencies
      more than 60 ms, including N-200 and P-300 waves. By contrast, halothane did not
      affect primary components with less than 95 ms latencies and suppressed the
      latest components. Hence, ketamine suppresses the nonspecific afferent pathways
      and the brain structures responsible for memory and emotional functions, while
      halothane does not affect the afferent pulsation and partially suppresses
      emotional and mnemonic functions.

PMID- 10900709
TI  - [The adequacy of patient protection from surgical trauma under spinal
      anesthesia].
AB  - Efficiency of various methods of anesthesia in prevention of the CNS segmented
      structures hyperreactivity induced by surgical trauma ware studied in 554
      patients during planned orthopedic operations and operations on the pelvic
      organs. Spinal anesthesia played the crucial role in prevention of induced
      hyperreactivity of nociceptive neurons of the posterior spinal horns. A notable
      alleviation of postoperative pain in patients operated on under spinal anesthesia
      was a clinical confirmation of this fact. Analysis of the time course of the
      amplitudes of the control and test H-reflexes before and after the intervention
      showed that spinal anesthesia largely prevented perioperative changes in the
      spinal neuromotor stimulation and, from this viewpoint, can be regarded as the
      optimal method of anesthesia in surgery on the lower part of the trunk.

PMID- 10900711
TI  - [Combined anesthesia using Diprivan and ketamine in pediatric surgery].
AB  - A total of 120 children aged 7-14 years were subjected to short-term elective and
      urgent interventions under combined intravenous anesthesia with diprivane and
      ketamine. The patients were divided into groups depending on methods of general
      anesthesia. Noninvasive monitoring of hemodynamic parameters and SaO2 was carried
      out during anesthesia and surgery and psychomotor functions were evaluated during
      the immediate postoperative period. Ketamine ensured stable hemodynamics during
      induction anesthesia. A combination of diprivane and ketamine levelled some
      untoward effects of these anesthetics.

PMID- 10900712
TI  - [An assessment of the efficacy of stress-protector pharmacological preparations
      and hyperbaric oxygenation in patients in the perioperative period].
AB  - Modulating effects of some drugs and HBO on adaptation reaction have been studied
      in 74 surgical patients. Investigation methods included cardiac rhythm record
      (statistical analysis with histogram plotting--sympathetic activity index),
      tcpO2, tcpCO2, SaO2, finger pulse amplitude (vasomotor tone evaluation), and
      evaluation of changes in arterial pressure and heart rate. The treatment included
      intravenous propranolol (0.92-1.38 micrograms/kg/min) or cordanum (1.85-2.7
      micrograms/kg/min) or clonidine (0.018-0.037 microgram/kg/min) or dalargin (0.55
      0.83 microgram/kg/min) HBO-100% O2 for 1 h at 1.5 ATA during increase of
      sympathetic activity. The results indicate that all drugs and HBO modulate the
      adaptation response of the organism and improve the outcomes of surgery.

PMID- 10900714
TI  - [The efficacy of using blood-saving technologies in operations on the heart and
      aorta].
AB  - Application of blood-saving methods during open-heart and aorta surgeries is
      discussed as exemplified by 86 patients. Platelet-rich plasma was prepared before
      surgery and infused during heart valve replacement, which decreased the
      postoperative blood loss 1.5 times. Reinfusion of patient's blood during
      aortocoronary shunting decreased the need in fluid replacement by 67% and
      utilization of the Cell Saver device in surgery on the aorta decreased the needed
      amount of donor blood by 50%.

PMID- 10900715
TI  - [Ways to decrease blood loss during total hip joint endoprosthesis].
AB  - Total replacement (endoprosthesis) of the hip joint was carried out in 93
      patients aged 18-60 years. Sixteen operations were performed under prolonged
      epidural blockade, 66 under neuroleptanalgesia, and 16 under ataralgesia. A
      deficiency of circulating blood volume was detected in all patients before
      surgery. The lowest mean arterial pressure was recorded in the prolonged epidural
      block group, while in the neuroleptanalgesia and ataralgesia groups the mean
      arterial pressure was virtually the same. Isovolemic hemodilution in patients
      with preoperative deficit of circulating blood volume decreased blood loss during
      long traumatic operations. Prolonged epidural blockade in combination with
      isovolemic hemodilution and spontaneous respiration led to a notable (70%)
      decrease of the true blood loss in comparison with the traditional
      neuroleptanalgesia.

PMID- 10900713
TI  - [The anesthesiological procedure for correcting preloading in the surgery of
      acquired mitral valve defects].
AB  - Intraoperative correction of preload in patients with acquired valvular disease
      (AVD) complicated by right-ventricular failure and severe pulmonary hypertension
      necessitates search for pathogenetically based algorithms of anesthesiological
      strategy. The objective of this study was to develop a strategy of assessing and
      treating the preload at the stage of induction anesthesia in patients with right
      ventricular failure. During surgery central hemodynamic parameters and their
      response to a short head-down-tilt (15-20 degrees) were evaluated in patients (n
      = 42) with cardiac index (CI) less than 2 l/min/m2 after induction anesthesia.
      The patients were divided into 2 groups with different severity of preoperative
      status. Group 1 (main) included 24 patients with stages II-III cardiac failure
      (according to N. Strazhesko and B. Vasilenko) and group 2 (control) consisted of
      18 patients with stage IIA cardiac failure. Progressing preoperative cardiac
      failure resulted in decrease of cardiac index and failure of compensatory
      hemodynamic mechanisms in AVD patients. The level of right-ventricular preload,
      pulmonary resistance, and stroke index were lower in group 1 than in the
      controls; however, 8% of group 1 patients responded positively to increased
      preload. In the control group 50% responded favorably to head-down-tilt. Hence,
      comprehensive assessment of cardiac index, central hemodynamic parameters and
      their response to head-down tilt help individually choose the anesthesiological
      strategy.

PMID- 10900716
TI  - [A scale for estimating multiple organ dysfunction in surgical patients].
AB  - A scale is proposed for estimating the severity of multiple organ dysfunction in
      surgical patients and its changes in the course of treatment. The scale was tried
      in 37 patients after abdominal operations. Estimations performed by means of the
      scale ore revealed good correlation with the patient's clinical status. Routine
      parameters are used in the scale, which facilitates its utilization in any
      surgical intensive care. The scale helps evaluate the severity of each system
      damage.

PMID- 10900717
TI  - [Abdominal sepsis: the integral assessment of the severity of patient condition
      and of multiple organ dysfunction].
AB  - Results of examinations of 247 patients with diffuse peritonitis and symptoms of
      abdominal sepsis are analyzed. Systemic inflammatory reaction in peritonitis
      patients can manifest by sepsis, severe sepsis, and infectious toxic (septic)
      shock. The severity of systemic inflammatory reaction syndromes can be evaluated
      by objective scores for evaluation of clinical states (APACHE II, SAPS) and the
      degree of multiple organ dysfunction/failure (MODS, SOFA). Application of
      objective scores for evaluation of clinical states provides clinical
      stratification of abdominal sepsis, helps predict the disease course and outcome,
      and improve treatment strategy.

PMID- 10900718
TI  - [Lactate kinetics during constant hemodiafiltration in critically severe patients
      with the systemic inflammatory response syndrome and multiple organ failure].
AB  - High-volume hemodiafiltration is a new approach to the treatment of critical
      patients with generalized inflammatory reaction and multiple organ failure.
      Increase of the liquid exchange during the procedure is fraught with the
      development of secondary metabolic disorders in cases when lactate-based buffer
      is used (with high amounts of lactate). This study was undertaken to evaluate the
      consequences for the acid-base balance in patients with hypoxia and circulatory
      failure. Twelve patients (6 men and 6 women) with APACHE II score 25 were
      examined. The major treatment modality was continuous hemodiafiltration. The
      results indicate that lactate-buffered solutions can be used in critical
      patients, because they do not cause a notable increase in the blood lactate
      levels due to its good utilization. Moreover, it is associated with correction of
      disorders in acid-base balance. No negative clinical consequences were observed
      after using lactate anion in high concentrations as the major buffer compound.

PMID- 10900719
TI  - [Disorders of purine metabolism in patients with peritonitis complicated by
      sepsis].
AB  - Progressive hypoxia and cell destruction leading to increased production of
      active oxygen forms by xanthinoxidase and manifesting by an increased level of
      uric acid in the blood in parallel with inhibited pentose cycle reaction due to
      low activity of glucose-6-phosphate dehydrogenase determine the severity of
      peritonitis.

PMID- 10900720
TI  - [The lipid peroxidation processes and the antioxidant system in the dynamics of
      an experimental Pseudomonas aeruginosa intoxication].
AB  - Lipid peroxidation and antioxidant defense processes have been studied over the
      course of experimental Pseudomonas aeruginosa intoxication in albino rats
      injected with a lethal dose of exotoxin A. The development of intoxication is
      associated with intensification of lipid peroxidation, manifested by accumulation
      of malonic dialdehyde and diene conjugates and decreased peroxide resistance of
      erythrocytes. Superoxide dismutase and catalase activities were inhibited and the
      concentration of vitamin B dropped. Injection of antioxidant alpha-tocopherol or
      antihypoxant gutimine at the late stage of intoxication did not notably modify
      the studied parameters.

PMID- 10900722
TI  - [The concept of the development of multiple organ failure in a model of
      gestosis].
AB  - Mechanisms of development of multiple organ failure (MOF) in gestosis have been
      studied. Analysis of the findings of examinations of 95 women with gestosis
      hospitalized in intensive care wards of Institute for Maternity and Neonatality
      Protection demonstrated that elements of the systemic inflammatory response
      syndrome (SIRS) underlie the development of MOF syndrome in gestosis, which can
      be diagnosed starting from early terms of gestation.

PMID- 10900721
TI  - [Prognosis, monitoring and intensive therapy in the prevention of the development
      of hemorrhagic complications in labor].
AB  - Blood clotting system has been studied over the course of pregnancy. The detected
      close correlations between hemostasiograms and labor hemorrhages suggested the
      possibility of predicting hemorrhagic complications. Based on informative signs,
      the authors formulate the rules for predicting hemorrhagic complications of labor
      starting from the first trimester and define the algorithm of monitoring the
      hemostasis system. Application of this system helped decrease the incidence of
      labor hemorrhages by half by means of appropriate preventive therapy.

PMID- 10900723
TI  - [Efferent methods in the therapy of puerperal and postoperative complications].
AB  - Ninety-six patients with chorioamnionitis in labor were treated. Clinical
      observations and laboratory findings demonstrated high efficiency of multiple
      modality treatment including use of efferent methods: plasmapheresis, incubation
      of cell mass with antibiotics, and ultra-violet exposure of the blood.

PMID- 10900724
TI  - [The current principles of the intensive therapy of the suppurative-septic
      complications after a cesarean section operation].
AB  - The results of treatment of 25 patients with septic complications after cesarean
      section are analyzed. Clinical and laboratory data demonstrate the efficiency of
      combined therapy including intraosseous injections of antibiotics,
      plasmapheresis, and UV blood exposure.

PMID- 10900725
TI  - [The current aspects of perioperative nutritive support].

PMID- 10900726
TI  - [Pulmonary hemodynamics during different regimens of AMV in patients with severe
      craniocerebral trauma].
AB  - Investigation of pulmonary hemodynamics were carried out in 26 victims operated
      on for brain compression with intracranial (epi-, subdural, and intracerebral)
      hematomas in combination with severe contusions during different regimes of
      artificial ventilation of the lungs (VCV, VCV + PEEP, PCV). Intracranial pressure
      and cerebral perfusion pressure were evaluated. The results indicate that in
      patients with severe craniocerebral injury PCV decreased systolic pulmonary
      artery pressure, total pulmonary resistance, central venous pressure,
      intracranial pressure, increased cerebral perfusion pressure, and therefore the
      pressure cyclic mode is pathogenetically validated in this patient population.

PMID- 10900727
TI  - [A case of respiratory distress syndrome complicated by the development of
      interstitial emphysema and pneumomediastinum].
AB  - A 15-year-old patient has been admitted to the intensive care unit for severe
      respiratory distress syndrome that developed as a result of pneumonia.
      Interstitial lung edema was confirmed by computer-aided tomography. It was
      successfully treated by positive pressure ventilation (PPV). Although PEEP did
      not exceed 7 cm H2O, PPV was complicated by interstitial emphysema,
      pneumomediastinum, and bilateral pneumothorax as a result of barotrauma.
      Pulmonary artery pressure (PAP) and pulmonary capillary wedge pressure (PCWP)
      were monitored. High PCWP values were inconsistent with the diagnosis of acute
      respiratory distress syndrome. The authors suggest that high PCWP was caused by
      high intraalveolar pressure, pneumomediastinum, and venule constriction in the
      hypoxic sites of the lung.

PMID- 10900728
TI  - [Sepsis on the threshold of the 21st century: the basic results. New problems and
      the immediate tasks].
AB  - The authors validate their positions in terminology of sepsis and evaluation of
      its severity, based on analysis of this problem evolution during the century,
      review of the most significant publications, and their own findings. Problems of
      intensive care are discussed. The authors claim that intensive care methods
      should be determined by the phase of the systemic inflammatory response syndrome
      (SIRS). One of the nearest goals for scientists and public health managers is an
      interdisciplinary consensus on terminology of sepsis and diagnostic criteria,
      creation of a standard protocol of laboratory studies and treatment, search for
      available markers of SIRS of infectious origin, regulation of cytokine response,
      creation of local data bases reflecting the etiological structure of the agents
      and their antibiotic resistance.

PMID- 10900729
TI  - [The etiological and pathogenetic characteristics of nosocomial pneumonia related
      to AMV (NP AMV)].
AB  - The author reviews modern data on the classification, epidemiology, etiology, and
      main risk factors of ventilator-associated pneumonias, the most severe
      complication of prolonged artificial ventilation of the lungs. Special attention
      is paid to the pathogenesis of this type of nosocomial pneumonia.

PMID- 10900731
TI  - [Extracts of the report of the National Advisory Committee on Ethics "The end of
      life, the termination of life, euthanasia"].

PMID- 10900732
TI  - [Median and long-term complications of splenectomy].
AB  - Splenectomy was one of the most common operations in abdominal surgery. During
      the past decade, an increased rate of late complications, especially septic and
      thromboembolic complications occurring after splenectomy, have been reported. The
      septic complications are well documented. The risk is related to the indication
      of splenectomy, and is less than 1% in adults without immunodeficiency. However,
      these overwhelming postsplenectomy infections are associated with a high
      mortality rate, about 50%. The best treatment of these infections is preventive
      measures which are based on vaccination and education of asplenic patients. The
      thromboembolic complications are rare, little studied, and specific preventive
      procedures have not been implemented.

PMID- 10900730
TI  - [Computer tomography scanning for acute appendicitis in adults: latest fad or
      real progress?].

PMID- 10900733
TI  - [Is it useful to maintain specific scores for the early determination of the
      severity of acute pancreatitis?].
AB  - STUDY AIM: Acute pancreatitis (AP) is a potentially life-threatening disease in
      which specific severity scoring system has been developed. The aim of this
      prospective study was to compare efficiency of the general severity of illness
      scoring system and the most widely used specific scoring system of AP in order to
      simplify the initial monitoring of AP at the time of admission. PATIENTS AND
      METHODS: Eighty-seven patients with AP were hospitalized in the same center.
      There were 47 men and 40 women (mean age: 57 +/- 16 years). Specific scores
      (Ranson, Imrie, Blarney) and general severity of illness scores (SAPSI, SAPS II,
      Apache II) were calculated for each patient. Radiological scores (Hill,
      Balthazar) were also calculated when TDM was early performed (80%). Each scoring
      system was correlated with severity, morbidity and mortality of AP and its
      predictive value evaluated by the area under the ROC curve. RESULTS: Aetiology of
      AP was predominantly biliary (20%) and alcoholic (70%). Eight per cent of the
      patients died and 29% of AP were classified as severe according to the Atlanta
      Congress Score. Morbidity rate was 40%. All the scoring systems were
      significantly correlated with mortality and exhibit ROC curve area between 0.77
      and 0.84, resulting in a similar prediction of death. CONCLUSION: Specific
      scoring system and general severity of illness scoring system have the same
      predictive efficiency in acute pancreatitis. The use of the specificity scoring
      system seems to be no more justified in acute pancreatitis.

PMID- 10900734
TI  - [Complicated colonic diverticulosis. Results of surgical treatment between 1981
      and 1998 in 370 patients].
AB  - AIM OF THE STUDY: The aim of this retrospective study was to analyze case reports
      of all the patients with complicated diverticular disease of the colon admitted
      in the same surgical center during an 18-year period and to report the
      postoperative results in patients operated on in emergency and in patients
      operated on electively. PATIENTS AND METHOD: From 1981 to 1998, 501 patients were
      admitted for complicated diverticular disease. There were 233 men and 268 women.
      Mean age was 66 years (range: 27-96). One hundred and thirty-one patients were
      only treated medically and 370 patients were operated on, either as an emergency
      (n = 211) or electively (n = 159). The complicated diverticular disease was
      located on the left colon in 362 cases and in the right colon in 8 cases.
      RESULTS: In the emergency group, 103 patients were operated on for pelvic (n =
      24) and generalized purulent (n = 67) or stercoral (n = 12) peritonitis, mainly
      with Hartmann procedure (n = 80) with 14 postoperative deaths; 67 were operated
      on for pericolic abscess with 6 deaths, 19 for colonic obstruction with two
      deaths and 22 for profuse hemorrhage with 4 deaths. The overall postoperative
      mortality rate was 12.3%, and morbidity rate 38.7%. Intestinal continuity was
      restored in 74% and eventrations were present in 10%. In the elective group,
      there were two postoperative deaths in patients with a colic fistula (n = 30), no
      mortality and a 10.8% morbidity rate in the other patients (n = 129). CONCLUSION:
      This series of an 18-year duration emphasizes the severity of surgery for acute
      complications in diverticular disease of the colon and the advantages of elective
      surgery. Large progress in the management of peritonitis and pericolic abscesses
      has made possible the improvement of their prognosis.

PMID- 10900735
TI  - [Hysterectomy for benign lesions: peroperative and early postoperative
      complications].
AB  - OBJECTIVE: Although hysterectomy for benign disorders is a routine and usually
      well-tolerated procedure, complications do occur, and the resulting morbidity
      rates are not negligible. The aim of this prospective study was to report
      perioperative and early postoperative complications observed after hysterectomy,
      regardless of the route or the operator. PATIENTS AND METHODS: Between March 31,
      1991 and December 14, 1998, 1,604 patients (mean age: 46.5 +/- 8.1 years)
      underwent an hysterectomy for benign disorders. Perioperative and early
      postoperative complications, in the 1,248 vaginal hysterectomies (77.9%), 190
      laparoscopically-assisted vaginal hysterectomies (11.9%) and 166 abdominal
      hysterectomies (10.2%) were noticed in each group and compared. RESULTS: None of
      the patients died in this series. Lesions on the urinary tract included 15
      bladder injuries (0.9%) and 1 ureter injury (0.06%) without significant
      difference between routes. There were 9 (0.6%) intestinal injuries, with a
      significant increase when laparotomy was performed (2.4%). In 45 patients (2.8%),
      bleeding exceeded 500 mL: and vaginal hysterectomy caused significantly fewer
      cases of heavy bleeding (2%, p < 0.001) than either laparotomy (6.7%) or
      laparoscopy (5.3%). The overall reoperating rate was 0.8% and this does not
      differ with the type of the procedure. CONCLUSION: Peri- and early postoperative
      complications after hysterectomy for benign disorders are not a rare event. In
      order to control complications and decrease the morbidity, a high-risk population
      should be defined based on the patients' history of pelvic surgery and
      endometriosis, on their parity and the size of their uterus. For these patients,
      the most appropriate route should be preferred and complications should be
      assessed using different tests and subsequently treated during the same
      procedure.

PMID- 10900736
TI  - [Surgery for primary hyperparathyroidism in 1998. Apropos of 66 patients and 3
      methods of approach].
AB  - STUDY AIM: The aim of this prospective study was to assess the advantages and
      disadvantages of cervicotomy, selective lateral approach and video-assisted
      surgery in the treatment of primary hyperparathyroidism (HPT 1). PATIENTS AND
      METHODS: During 1998, 66 patients were operated on for HPT 1 in the same center.
      There were 48 women and 18 men (mean age: 58 years, range: 21-84), familial HPT 1
      or MEN1 excluded. The interventions were performed via classical cervicotomy (n =
      32), via selective lateral approach (n = 8) and were video-assisted (n = 25). A
      mediastinal adenoma was removed via cervicotomy and another one via left
      thoracoscopy. The procedure was associated with intraoperative parathormone (PTH)
      quick-assay. Calcium testing was controlled before leaving the hospital and 2
      months later. RESULTS: A double adenoma and 65 single adenomas were confirmed by
      pathological report. Circulating PTH levels, 20 minutes after removal of the
      adenoma, always decreased significantly. In video-assisted procedures, there were
      11 conversions to open cervicotomy (44%) and morbidity consisted of one case of
      laryngeal nerve paralysis. At the end of the study, all patients except one had a
      normal calcium level. CONCLUSION: Video-assisted parathyroidectomy is feasible
      but requires a preoperative localisation of the adenoma and intraoperative PTH
      quick-assay. Its main benefit in cervical adenoma is to reduce the scar and in
      mediastinal adenoma to avoid sternotomy. With the elective approach, results are
      similar to those of video-assisted surgery and the procedure is much easier to
      perform. Classical cervicotomy is still the best option in case of previous
      cervicotomy, of simultaneous thyroidectomy, of negative preoperative imaging and
      in elderly patients less concerned about cosmetic benefit.

PMID- 10900737
TI  - [Peritoneal hydatid cysts. Apropos of 12 cases].
AB  - STUDY AIM: The aim of this retrospective study was to report on 12 cases of
      peritoneal hydatidosis observed in the same hospital from 1989 to 1998. PATIENTS
      AND METHODS: Four men and 8 women (mean age: 37 years) were included in the
      study. Four of them had been operated on for liver hydatidosis, 3 to 9 years
      before. The peritoneal hydatidosis was asymptomatic (n = 2), revealed by pain
      and/or fever (n = 9) and by hydatid peritonitis (n = 1). Diagnosis was performed
      by ultrasonography in seven cases out of 10. Preoperative treatment with
      albendazole was given to one patient only during 1 month. All patients were
      operated on. Peritoneal cysts, with different locations, were secondary in 11
      patients. Nine patients had concomitant liver hydatidosis and two concomitant
      retroperitoneal hydatidosis. Hydatid cysts were usually sterilized with oxygen
      water and treated by resection of the protruding dome. Postoperative treatment
      with albendazole was given to five patients. RESULTS: Postoperative complications
      occurred in five patients: intestinal occlusion, abscess in a residual cavity,
      purulent fistulas, biliary fistulas with a favorable issue. With a mean 38-month
      follow-up, all patients were alive, with only one recurrence in a liver hydatid
      cyst. CONCLUSION: Peritoneal hydatidosis was secondary in 11 out of 12 patients.
      Diagnosis was performed with ultrasonography in seven out of 10 patients. All
      patients were operated on. With a mean follow-up of 38 months, only one
      recurrence has been observed.

PMID- 10900738
TI  - [Electronic detection of breaks in the surgeon-patient barrier. Evaluation of
      protective clothing in visceral surgery].
AB  - STUDY AIM: Breakdown of the aseptic surgeon-patient barrier causing abnormal
      contact between skin and body fluids represents a risk for transmission of
      infectious disease. Such breakdowns are frequently not perceived by the surgical
      team over prolonged periods. The aim of this prospective randomized study was to
      evaluate the protection afforded by double gloving and reinforced gowns in
      visceral surgery. METHODS: An electronic device detected breakdowns of the
      surgeon-patient barrier in a series of 80 surgical procedures, randomly assigned
      to double or single gloves, and normal or reinforced gowns. Fluid contacts due to
      glove perforation, glove porosity or gown wetting were recorded during 151
      individual participations covering 238 hours. Surgical procedures were called
      deep for incisions of more than 10 cm. RESULTS: Deep surgical procedures carried
      a sevenfold-increased risk of barrier breakdown, compared with superficial ones.
      Skin contacts through wet gowns were not prevented by the use of double thickness
      materials, but double gloving reduced the number of perforation and porosity
      alarms twofold in both superficial and deep surgery. CONCLUSION: Without
      electronic detection, 96% of barrier breakdowns would remain undetected by the
      surgical team and lead to prolonged contact with potentially contaminating
      fluids. The use of double gloving provides a real protection against
      contamination risk.

PMID- 10900739
TI  - [Fundamental principles and pitfalls linked to the use of ultrasonic scissors].
AB  - In an ultrasonically activated device, electric energy is transformed to
      mechanical vibration, which is transmitted to the device's tip. By clamping the
      vessel between the tissue pad and vibrating blade, frictional heat is generated.
      This heat, significantly milder than that in electrocautery technique, is ideal
      for sealing the vessel. The ultrasonic vibration eventually divides the vessel.
      In the experimental studies, the cut end of medium-sized vessels divided by a
      scissor type ultrasonically activated device (USAD) withstood high intravascular
      pressure. However, our clinical experiences with the USADs suggest there are
      pitfalls including:--giving excessive tension to the vessel,--incomplete clamping
      of the vessel,--contacting the adjacent vessel with the back side of the active
      blade tip,--contacting the adjacent vessel with the blade tip. Some devices are
      described to prevent these pitfalls.

PMID- 10900740
TI  - [Use of a water-jet dissector during hepatectomy].
AB  - STUDY AIM: A new water jet cutting system was used by an hepatobiliary surgical
      team for hepatectomy in ten patients. The aim of this retrospective study was to
      assess advantages and disadvantages of this new apparatus for liver dissection.
      MATERIAL AND METHOD: This procedure uses the mechanical power of water jet under
      pressure in the liver incision. The study concerned feasibility of the
      hepatectomy, the ease of use of the apparatus and volume of the blood loss.
      RESULTS: The water jet was very easy to use and of maintenance (bag of sterile
      saline in a non sterile pressurized container, disposable handpiece). Any liver
      resection could be performed using this tool, independently of the liver
      consistency. There was no decrease in the duration of surgery and the blood loss
      compared to the ultrasonic cutting system. Minor splashing, bubbles and mist
      impaired the accuracy of the vascular dissection. CONCLUSION: The water jet
      dissector used in this series is a simple, economic and useful tool to perform
      liver resection.

PMID- 10900741
TI  - [Liver transplantation with a graft taken from a heart transplant patient who was
      brain-dead].
AB  - The shortage of organ donors has led to progressive softening of selection
      criteria for organ donation. We report on hepatic transplantation in a 55-year
      old woman with primary biliary cirrhosis, whose donor was a 50-year-old heart
      transplant recipient who became brain stem dead, due to cerebral bleeding 8
      months after transplantation. An orthotopic liver transplantation was performed.
      The postoperative course was uneventful and the recipient was alive and had
      normal liver function after a 42-month follow-up. Analysis of the literature
      included ethical consideration, potential hepatotoxic effects of
      immunosuppressive drugs and modification of the graft immunogenicity. It confirms
      that transplanted patients should not be a priori excluded from organ donation.

PMID- 10900742
TI  - [Surgical abstention in closed injuries of the spleen].
AB  - Splenic conservation avoids the overwhelming postsplenectomy infection. The high
      percentage of patients treated by noninvasive procedures would be due to the
      simple clinical course of splenic trauma and precision of diagnosis, using CT
      scan. Only clinical evaluation could provide further information on the
      indications for surgical treatment, as there is no available score regarding the
      value of CT scan for choosing the therapeutical option. Non-operative management
      of splenic ruptures should be considered in selected patients in whom
      hemodynamics is stable and closely monitored.

PMID- 10900743
TI  - [Protection methods in the operating room and risks of blood exposure. Results of
      a national survey].
AB  - A national survey was conducted with 5,000 randomly chosen surgeons in order to
      assess the methods of protection used or warranted in the operating room against
      blood-borne pathogens. The rate of complete vaccination against hepatitis B was
      79.2%. The use of double gloves was constant for 72% of orthopedist surgeons but
      only reached 28.2% for the overall surgical population. Only 46.1% of the gowns
      used were coated, though the quality of the barrier when it is wet is very risky.
      The protections taken in the operating room against blood-borne pathogens can be
      improved.

PMID- 10900744
TI  - [Abulcassis, the grand master of Arabian surgery].
AB  - In the tenth century Abulcassis lived in the rich caliphate of Cordoba, where he
      wrote Tarsif, his masterpiece, which truly corresponded to an encyclopedia whose
      last volume was devoted to bringing up to date the art of surgery.

PMID- 10900745
TI  - Surgery today

PMID- 10900746
TI  - [Diseases in affluence and in poverty].

PMID- 10900747
TI  - [Social factors and psychophysical well-being].

PMID- 10900748
TI  - [Socioeconomic context of cardiovascular diseases].

PMID- 10900749
TI  - [Economic progress and the impending pandemic of cardiovascular diseases].

PMID- 10900750
TI  - [The pandemic of cardiovascular diseases, available resources and international
      cooperation].

PMID- 10900751
TI  - [Cardiovascular risk in women: role of social status].

PMID- 10900752
TI  - [Social factors and survival in the "RIFLE" population].

PMID- 10900753
TI  - [Socioeconomic status and neoplasia].

PMID- 10900754
TI  - [Conditioning of social, economic, and cultural factors in the access to health
      services].

PMID- 10900755
TI  - [Natural resources and impact on community health].

PMID- 10900756
TI  - [Determinants of social inequalities in health in Italy].

PMID- 10900757
TI  - [Socioeconomic factors in surgery].

PMID- 10900758
TI  - [Child health in the north and the south of the world].

PMID- 10900759
TI  - [Nanobacteria. An experimental neo-lithogenesis model].
AB  - OBJECTIVE: To study the phenomenon of biomineralization in an experimental model
      of lithogenesis by percutaneous renal punction without laparotomy and no
      antibiotics. METHODS/RESULTS: The study comprised 4 Brown-Norway rats.
      Nanobacteria inoculum (X, 2X and 4X) was administered to three rats and the
      remaining one was used as control. The analytical and radiological findings
      showing the development of obstructive pyelocaliceal lithiasis in the kidneys of
      rats no. 2 and 3 are presented. CONCLUSIONS: Translumbar percutaneous renal
      puncture has permitted performing laparotoy without antibiotic coverage, which
      was the main difficulty of the experimental model of lithogenesis. Nanobacteria
      were cultured successfully, but not without difficulty, and formation of calculi
      in the rat pyelocaliceal system was achieved. This experimental model will
      provide further insight into lithogenesis and will allow us to find the answers
      to some of the many questions concerning this condition that remain.

PMID- 10900760
TI  - [Determination of NMP-22 as recurrence marker in bladder cancer. Preliminary
      study].
AB  - OBJECTIVES: The present study was conducted to determine the efficacy of NMP-22
      as a diagnostic test for recurrence of bladder tumors and to compare its efficacy
      with urine cytology. METHODS: 30 patients (25 male, 5 female), aged 41-87 years
      (mean 73.4), with bladder tumor were evaluated by cytology, cystoscopy and
      determination of NMP-22 at 3 and 6 months post-TUR of the bladder. A positive
      test was defined as NMP-22 greater than 10 U/ml. RESULTS: 80.7% were T1, 15.3% T2
      T3, 76.8% were grade I and II, and 23.2% were grade III. NMP-22 showed a
      sensitivity of 69%, a specificity of 64%, a positive predictive value of 52% and
      a negative predictive value of 78%, using tumor recurrence at 3 and 6 months as
      the unit of analysis, for a recurrence rate of 36%. Cytology showed a sensitivity
      of 44%, a specificity of 92%, a positive predictive value of 77% and a negative
      predictive value of 74%. When both tests were used, we obtained a sensitivity of
      87.5%, a specificity of 64.2%, a positive predictive value of 58.3% and a
      negative predictive value of 90%. In grade I tumors, determination of NMP-22 had
      a sensitivity of 100%, a specificity of 77.7%, a positive predictive value of 60%
      and a negative predictive value of 69%. CONCLUSIONS: NMP-22 showed an acceptable
      sensitivity but a low positive predictive value, therefore control cystoscopic
      evaluation cannot be avoided. The sensitivity and negative predictive values
      increased when NMP-22 and cytology are used in combination. We found NMP-22 to be
      a very useful marker for recurrence of low grade tumors.

PMID- 10900761
TI  - [Bacteriologic assessment of the lower urinary tract and genital area in patients
      with recurrent urinary tract infections].
AB  - OBJECTIVE: The pathogens responsible for urinary infection originate from the
      digestive tract prior passage through the genital region. Samples were obtained
      from this region in an attempt to identify women with these pathogens. We have
      analyzed the most frequently colonized areas of the genital region in order to
      develop a method for obtaining samples. Risk factors were evaluated by
      determining the relationship of the samples with factors implicated in the
      pathogenesis of recurrent infection. METHODS: Samples were obtained from 146
      women of all ages that consulted for recurrent urinary tract infection. The
      samples from the genital region (perimeatal vulva, vagina, urethral and
      intraurethral meatus) and urine obtained through a catheter were cultured.
      RESULTS: The overall incidence of positive samples was 41%; 23% of the patients
      showed urinary infection (urine obtained by catheterization) at the time the
      samples were taken. The vaginal samples were the most frequently colonized and
      the intraurethral samples were the most sensitive when compared with the urinary
      samples. The sensitivity, specificity, positive and negative predictive values of
      these two samples were the same as those of the other samples together. In regard
      to colonization, a difference was found only between menopausal and premenopausal
      women, and in proportion to the duration of the history of infection.
      CONCLUSIONS: The study shows that it is unnecessary to obtain various samples;
      vaginal and intraurethral smears are sufficient. Menopausal women who referred
      two symptomatic episodes a year were found to be at a higher risk for vaginal
      infection, and in proportion to the number of years they have had recurrent
      infection.

PMID- 10900762
TI  - [Epidermal growth factor receptor (EGFR) in the prognosis of bladder carcinoma.
      Experience of 5 years].
AB  - METHODS: From November 1992 to November 1993, a prospective study was conducted
      on 20 controls and 61 patients with bladder carcinoma. EGFR expression was
      determined by radioimmunoassay and the correlation of the results of histological
      analysis and the clinical course was analyzed. The follow-up period was from
      November 1992 to July 1998. The association between qualitative variables and the
      x2 or Fisher exact test was compared using the hypothesis of the proportional
      ordinal trend for the ordinal variables, and the quantitative variables were
      analyzed using Student's t test and/or variance analysis (ANOVA). Survival was
      analyzed by the Kaplan-Meier method and comparison was performed using the
      Breslow exact test. The Cox proportional hazards regression model was utilized.
      The SPSS software for Windows 7.0 was used for the analysis. RESULTS: The EGFR
      values were higher for patients with bladder carcinoma than in controls (14.48 vs
      2.54 fmol/mg of protein). EGFR values were higher in patients with superficial
      bladder tumor than in those with infiltrating tumors (27.03 fmol/mg vs. 10.05
      fmol/mg of protein; p = 0.000). Poorly differentiated tumors showed higher values
      of EGFR (6.73, 14.48 and 17.07 fmol/mg of protein for grades I, II and III,
      respectively; p < 0.05). The EGFR values were higher in patients that died from
      cancer during follow-up (64.8) than in those who died from other causes (47.5)
      and those who are alive and on follow-up (42). An increase in EGFR values did not
      carry a risk of death from cancer (p = 0.1269; ns). Analysis of the grade of
      tumor differentiation showed that for the more aggressive tumor grade, a positive
      EGFR was a sign of reduced survival. Survival in patients with superficial and
      infiltrating tumor did not appear to change significantly according to the EGFR
      value. EGFR determination was not useful in predicting recurrence and increased
      EGFR values did not correlate with a higher risk of recurrence. CONCLUSIONS: 1)
      The normal pattern of EGFR could not be established. 2) EGFR was not useful in
      identifying subgroups at risk of death. 3) Knowledge about these proteins
      synthesized by oncogenes offers new possibilities in the treatment of cancer.

PMID- 10900763
TI  - [Clinical usefulness of free PSA/total PSA ratio in the early diagnosis of
      prostatic cancer].
AB  - OBJECTIVES: To determine the clinical utility of free/total PSA ratio and PSA
      density in the early diagnosis of prostate cancer (patients with serum PSA
      between 4 and 10 ng/ml) and to determine the differences, if any, in the
      free/total PSA ratio in patients with cancer and those with benign prostatic
      hyperplasia (BPH). METHODS: A prospective and descriptive study was conducted on
      61 patients with low grade obstructive symptoms and total serum PSA between 4 and
      10 ng/ml (group 1), and 42 patients who underwent prostate surgery and had an
      anatomopathologically confirmed diagnosis of BPH (group 2). Free and total PSA
      were determined, as well as prostate volume by transrectal US, in all cases.
      Prostate biopsy was performed in all patients with a total PSA value between 4-10
      ng/ml. The sensitivity, specificity, positive and negative prognostic values of
      free/total PSA ratio and PSA density were analyzed. RESULTS: The mean age of the
      patients in group 1 was 67.7 years and 68.3 years in group 2. The mean prostate
      volume by US was 55.2 and 47.1, respectively (n.s.). The mean total PSA was 6.39
      ng/ml for group 1 and 5.73 ng/ml for group 2 (n.s.). No significant difference
      was found between the mean free PSA values of both groups. However, the
      free/total PSA ratio and PSA density were significantly different (p < 0.000). In
      group 1 (total PSA 4-10 ng/ml), prostate biopsy was positive in 32.8% of the
      patients. In this group of patients, there were no significant differences in the
      parameters analyzed. Application of different cutoffs for both tests showed a
      higher clinical utility for the 0.24-0.30 range. CONCLUSIONS: At similar mean
      prostate volume and mean total PSA, significant differences were found in the
      free/total PSA ratio and PSA density of patients submitted to surgery for BPH and
      those with a total PSA value of 4-10 ng/ml. However, these results were not
      observed when patients with PSA of 4-10 ng/ml were analyzed for presence or
      absence of evidence of malignancy in the prostate biopsy.

PMID- 10900764
TI  - [Epidemiology of urinary lithiasis in our Unit. Clinical course in time and
      predictive factors].
AB  - OBJECTIVES: To analyze the incidence of lithiasis and stone composition in our
      setting. The trend is compared with the results of the majority of studies on
      urinary calculi reported in the literature based on the number and composition of
      stones. METHODS: The study comprised patients referred to the Urolithiasis Unit
      of our hospital over the last 21 years. Stone composition was analyzed by infra
      red spectroscopy. The study period was divided into 4 time intervals: 1977-1979,
      1977-1980, 1977-1987 and 1977-1998 in order to determine the trends of the
      incidence of lithiasis in our setting. RESULTS: A total of 5516 patients were
      reviewed; of these, 766 had recurrence. The distribution was 385, 995, 3378 and
      5516, respectively. Calcium oxalate calculi showed an incidence of 61.3%, calcium
      phosphate 18.5%, uric acid 11.2%, infectious calculi (ammonium urate and ammonium
      magnesium phosphate) 6.6%, and finally the incidence of cysteine calculi was
      0.77%. Concerning the distribution according to sex, 62% of the males had calcium
      oxalate stones, 68% uric acid, 42.5% phosphate and 45% infectious lithiasis. The
      trends for uric acid, infectious, oxalate and phosphate calculi changed over
      time. CONCLUSIONS: There is a clear trend of calculi prevalence in the male,
      particularly oxalate and uric acid calculi. There is a trend for cysteine calculi
      to remain the same, calcium phosphate and oxalate calculi to increase, and uric
      and infectious calculi to decrease. The changes observed may be due to dietary
      changes and improvement in the quality of life.

PMID- 10900765
TI  - [Urinary incontinence in menopause].
AB  - OBJECTIVE: To determine if menopause increases the risk of developing bladder
      hyperactivity or stress urinary incontinence. METHODS: A case control study was
      conducted on 111 women, 57 with bladder hyperactivity and 54 controls without
      hyperactivity, and 55 cases with stress urinary incontinence and 55 controls
      without stress urinary incontinence. The results were analyzed by multivariant
      logistic regression for the influence of age. RESULTS: A relationship was found
      between age and menopause and the risk of developing stress urinary incontinence.
      No relationship was found between bladder hyperactivity and age or menopause. Age
      was found to be a negative factor of menopause in regard to the risk of
      developing stress urinary incontinence. CONCLUSIONS: The risk of developing
      stress urinary incontinence in menopausal women decreases with age and disappears
      after age 52.

PMID- 10900766
TI  - [Pulsed dye laser vs EKL-Compact lithotriptor in the treatment of distal ureteral
      lithiasis].
AB  - OBJECTIVES: Our results in the treatment of distal ureteral calculus with pulsed
      dye lasertripsy (Pulsolith) and the EKL-Compact (Olympus) electrokinetic
      lithotriptor are analyzed. METHODS: The time interval compared was 12 months for
      both cases; lasertripsy was utilized in 57 and electrokinetic energy in 61 cases.
      All patients underwent IVP or radiological and/or US evaluation of the urinary
      tree to determine the size and location of the calculus, and a complete routine
      presurgical assessment. Epidural anesthesia was administered in all patients, as
      well as prophylactic antibiotics. The approach and endoscopic technique using the
      7.9-9.8 FR ureteroscopes (Olympus), stone removal with long forceps and ureteral
      dilatation with the Uromat hydraulic pump are described. All but 9 patients had a
      5 FR catheter indwelling for 24 hours to avoid the postureteroscopy colic pain
      caused by perilithiasic ureteral edema. RESULTS: Our success rate was 93% for
      both modalities of stone fragmentation. Fragmentation with ultrasound was
      required in 4 cases of failed lasertripsy and 3 cases of failed lithotripsy with
      electrokinetic energy. There were 7 cases with mucosal laceration from
      ureteroscope insertion and punctate mechanical perforation of the ureteral mucosa
      produced by the laser fiber. There were no complications with the use of EKL-C
      except for small areas of petechiae. CONCLUSION: Analysis of our results for both
      treatment modalities, as well as their advantages and disadvantages, showed stone
      fragmentation with the EKL-C to be the treatment of choice. We have utilized this
      system in our unit since December 1994 because of its efficacy. Furthermore, it
      is easy to use, to transport inside and outside the hospital, easy to assemble
      and low-cost.

PMID- 10900767
TI  - [Advantages of a new kit for the determination of antisperm autoantibodies].
AB  - OBJECTIVES: It has been widely demonstrated that there is an increased level of
      sperm autoantibodies (SAA) in infertile than in normal fertile men, suggesting
      this could be a cause of infertility. This study was designed to correlate the
      direct agglutination methods of TAC II (a kit developed and validated by our
      staff) and the MAR-Screen (Fertility Technologies, Natick M.A., Bioscreen Inc.).
      METHODS: 645 semen samples from patients who consulted for infertility at the
      Infertility and Urology services of the Provincial del Centenario and Eva Peron
      de Granadero Baigorria teaching hospitals in Rosario (Argentina) and 30 fertile
      controls were analyzed. RESULTS: Statistical analysis showed a sensitivity of
      87%, a specificity of 100%, a positive predictive value of 100% and a negative
      predictive value of 98% for TAC II. CONCLUSIONS: We recommend the use of TAC II.
      It has similar methodological characteristics as the MAR-Screen method and offers
      some advantages, such as the possibility to perform analysis on frozen sperm
      samples and oligospermic patients, since it is not necessary for the spermatozoa
      to be moving. Furthermore, the test has a higher immunological specificity
      because spermatozoa are washed.

PMID- 10900768
TI  - [Nephrogenic adenoma. Report of 4 new cases].
AB  - OBJECTIVE: Four additional cases of nephrogenic adenoma are described. METHODS:
      The clinical records of patients with nephrogenic adenoma that had been diagnosed
      at our hospital from 1994 to 1999 were reviewed. RESULTS: The most frequent
      localization was the urinary bladder and it was more prevalent in middle-aged
      men. This condition usually presented as a histological finding in the course of
      follow-up or treatment of other bladder conditions by TUR or cystectomy. Biopsy
      is fundamental for diagnosis. CONCLUSIONS: Nephrogenic adenoma is a rare benign
      metaplastic lesion of the urinary tract that appears to result from chronic
      irritative stimulus to the urothelium. The treatment of choice is by
      transurethral resection. Although no case of progression to malignancy have been
      detected, long-term follow-up by endoscopy and ultrasound is advocated due to its
      predispositon to recurrence.

PMID- 10900769
TI  - [Differential diagnosis of intrascrotal calcification: lithiasis attached to
      hydrocele wall].
AB  - OBJECTIVE: To report a case of scrotal calculus in a hydrocele, attached to the
      parietal portion of the tunica vaginalis, complicating the differential
      diagnosis. METHODS: A 54-year-old patient with a clinical diagnosis of hydrocele
      is described. Ultrasound confirmed the diagnosis and demonstrated a calcified
      structure in the hydrocele fluid, attached to the parietal portion of the tunica
      vaginalis. A calculus of 1.7 cm diameter was found during the surgical procedure.
      CONCLUSION: The presence of calculus in a hydrocele does not change the prognosis
      or treatment of this condition, although some doubts may arise during sonographic
      assessment if it is attached to the parietal portion of the tunica vaginalis.

PMID- 10900770
TI  - [Retroperitoneal bronchogenic cyst mimicking adrenal gland tumor].
AB  - OBJECTIVE: To report a case of retroperitoneal bronchogenic cyst, an anomaly
      during the development of the primitive anterior intestine from which the bronchi
      and lungs are developed. METHODS/RESULTS: A 38-year-old male presented with left
      lumbar pain. Patient evaluation disclosed a left adrenal polycystic mass which
      was removed by surgery. Pathological analysis of the surgical specimen
      demonstrated a bronchogenic cyst. This case is compared with some of the few
      cases reported in the literature. CONCLUSIONS: Retroperitoneal bronchogenic cyst
      is a cause of retroperitoneal tumors in the splenic or hepato-renal region.
      Although it is uncommon, it should be taken into account when making the
      differential diagnosis.

PMID- 10900771
TI  - [Penile primary melanoma; report of a case].
AB  - OBJECTIVE: An uncommon variant of penile tumor associated with chronic lymphoid
      leukemia is presented. METHODS/RESULTS: A case of primary melanoma of the penis
      associated with chronic lymphoid leukemia is presented. Diagnosis was based on
      the anatomopathological findings. Lymph node involvement could not be determined
      due to the associated leukemia. Conservative management was instituted due to the
      patient's age. CONCLUSIONS: Primary melanoma of the penis is a very aggressive
      and uncommon tumor. To our knowledge, less than 140 cases have been reported.
      Hyperpigmented lesions must be biopsied to rule out melanoma.

PMID- 10900772
TI  - [Long course metastasis in renal adenocarcinoma. Adrenal gland involvement].
AB  - OBJECTIVES: To report two cases of metachronic adrenal metastasis (one
      contralateral and the other bilateral) from renal cell carcinoma with long
      survival. METHODS: Two patients with clear cell renal carcinoma that developed
      metastasis to the adrenals are described. Each patient had undergone three
      operations for solitary metastasis during the 8-years follow-up. The indications
      for the surgical management of solitary metastasis, morbidity, prognosis and
      recent investigational treatment possibilities reported in the literature are
      analyzed. RESULTS: Resection of the renal cell carcinoma achieved a survival of
      more than 8 years with a good quality of life and no significant surgical
      complications. The outcome, however, is poor. CONCLUSIONS: Although there was no
      lymph node involvement and the tumor was localized to the renal parenchyma, one
      patient developed solitary lung metastasis and contralateral adrenal metastasis 4
      and 8 years after the initial diagnosis, respectively. In the other case,
      contralateral adrenal metastasis appeared three years later. The possibility of
      long-term metastasis to the adrenal gland should be taken into account due to
      renal vein involvement. Preservation of the adrenal gland at the initial surgery
      (lower pole tumor) led to adrenal metastasis 8 years after the initial diagnosis.
      The prognosis is poor in both cases and the situation is discouraging for the
      urologist.

PMID- 10900773
TI  - [Non-specific granulomatous epididymitis].
AB  - OBJECTIVE: A case of granulomatous epididymitis is presented. METHODS: A 23-year
      old patient consulted for nonspecific pain in the left supratesticular region.
      Physical examination showed a hard, indolent, enlarged epididymis. An ultrasound
      scan revealed normal testes with small bilateral hydrocele and left epididymal
      enlargement with calcifications. Resection was performed via the inguinal
      approach. RESULTS: The histopathological analysis demonstrated intense
      granulomatous reaction with multinucleated giant cells and foci of spermatozoal
      remnants. Staining for fungi and acid-fast bacilli were negative. CONCLUSION: The
      condition was diagnosed as nonspecific granulomatous epididymitis.

PMID- 10900774
TI  - [Multiple urethral lithiasis. Report of a case].
AB  - OBJECTIVE: To report a case of multiple urethral calculi, an uncommon urological
      condition in our setting. The clinical, radiological and therapeutic aspects are
      discussed and the literature is briefly reviewed. METHODS/RESULTS: A 77-year-old
      male consulted at the emergency services of our hospital for dysuria, pollakiuria
      and difficulty in voiding. The patient also referred and indurated area in the
      penile ventral aspect. Radiological examination disclosed three calculi in the
      penile urethra with were successfully removed by meatotomty and urethrolithotomy.
      The patient is currently asymptomatic. CONCLUSIONS: Urethral calculus is uncommon
      in developed countries. "Milking" is not advocated due to the high incidence of
      urethral injury. Treatment is by simple urethrolithotomy in combination with
      other techniques (urethroplasty, diverticulectomy, etc.), if required.

PMID- 10900775
TI  - Endoscopic injection sclerotherapy control of intractable hematuria following
      radiation-induced hemorrhagic cystitis. A novel approach.
AB  - OBJECTIVE: To establish the utility of endoscopic sclerotherapy using 1%
      ethoxysclerol for the control of intractable hematuria following post-irradiation
      telangiectatic cystitis (PTC). METHODS: Our experience of treating 4 patients
      (one female and three male) with massive exsanguinating hematuria resulting from
      PTC, using a combined intralesional and perilesional injection of 1%
      ethoxysclerol, is presented. Observation on the distribution, grading of
      telangiectasis and pattern of bleeding are made. RESULTS: A dramatic and lasting
      cessation of the hematuria in all the 4 patients was achieved during the follow
      up period varying from 1 month to 4 years. CONCLUSION: Endoscopic injection
      sclerotherapy is a simple, highly effective, less invasive new technique in the
      management of massive and intractable hematuria due to radiation-induced
      telangiectasia of the urinary bladder.

PMID- 10900776
TI  - Variation in contrasting forms of 'memorising' and associated observables.
AB  - BACKGROUND: There is a posited conceptual distinction in the student learning
      literature in higher education between contrasting forms of 'memorising': as a
      process of rehearsal which is usually equated with rote learning, and as a
      process of committing to memory material that in two separate senses is
      temporally either 'understood' before or after the event. AIMS: The present study
      reports on the operationalisation of these contrasting forms of 'memorising' and
      investigates their empirical association with one another, their gender
      sensitivity, and their joint association with other modelling sources of
      explanatory variation in student learning. SAMPLES: Two samples of entering first
      year economics students at the Universities of South Australia (N = 896) and
      Adelaide (N = 448) which are combined in the present study (N = 1344). The
      combined sample is further distinguishable by gender (females, N = 662, males, N
      = 682). METHOD: Students were surveyed prior to the commencement of lectures and
      reported retrospectively on their most recent school-based learning experiences.
      Resultant data in the form of inventory responses were subjected to exploratory
      and confirmatory factor analyses, multivariate analysis of variance, and
      correlation analysis. RESULTS: Empirically the three forms of 'memorising' are
      independent of one another and they are furthermore sensitive to gender-based
      response differences in terms of both location and structure. Forms of
      'memorising' are respectively associated in a theoretically congruent manner with
      'deep'-level processes, learning pathologies, and contrasting conceptions of
      learning. CONCLUSIONS: The unqualified use of 'memorising' in studies of student
      learning is contra indicated. Contrasting forms of 'memorising' represent
      discrete sources of explanatory variation that can be used to construct finer
      grained models of student learning in process terms.

PMID- 10900777
TI  - Working memory deficits in children with low achievements in the national
      curriculum at 7 years of age.
AB  - BACKGROUND: Close links between children's capacities to store and manipulate
      information over brief periods have been found with achievements on standardised
      measures of vocabulary, language comprehension, reading, and mathematics. AIM:
      The study aimed to investigate whether working memory abilities are also
      associated with attainment levels in the national curriculum assessments at 7
      years of age. SAMPLE: Eighty-three children aged 6 and 7 years attending local
      education authority schools participated in the study. METHODS: Working memory
      skills were assessed by a test battery designed to tap individual components of
      Baddeley and Hitch's (1974) working memory model. Children were assigned to
      normal and low achievement groups on the basis of their performance on national
      curriculum tasks and tests in the areas of English and mathematics. RESULTS:
      Children with low levels of curriculum attainment showed marked impairments on
      measures of central executive function and of visuo-spatial memory in particular.
      A single cut-off score derived from the test battery successfully identified the
      majority of the children failing to reach nationally expected levels of
      attainment. CONCLUSIONS: Complex working memory skills are closely linked with
      children's academic progress within the early years of school. The assessment of
      working memory skills may offer a valuable method for screening children likely
      to be at risk of poor scholastic progress.

PMID- 10900778
TI  - Bullying in Flemish schools: an evaluation of anti-bullying intervention in
      primary and secondary schools.
AB  - BACKGROUND: The positive of the Norwegian anti-bullying programme (Olweus, 1992)
      stimulated other countries to tackle bully/victim problems. However, outcome
      studies found rather low levels of effect or even inconsistent results. AIMS: The
      purpose of the present study was to evaluate behavioural effectiveness of a
      school-based anti-bullying approach within Flemish schools. In addition, specific
      attention was given to the relationship between outcome findings and external
      support. SAMPLE: A total of 18 schools, comprising 1104 primary and secondary
      school children were recruited for this study. Students ranged in age from 10 to
      16 years. METHOD: For this study, an experimental pre-test/post-test design was
      used which included a control group. Three groups were established. The first
      group, Treatment with Support, involved students from schools that implemented a
      school-based anti-bullying intervention with additional support from the research
      group. The second group, Treatment without Support, also involved students from
      schools that implemented a school-based anti-bullying programme. However, in
      contrast with those falling under the first condition, this group of schools
      could not appeal to the research group for additional help. The last group
      involved students from schools that did not implement the anti-bullying programme
      and served as a Control condition. Repeated measures analyses of variance were
      carried out. RESULTS: The findings regarding the effects of the school-based anti
      bullying intervention programme on the extent of bullying and victimisation
      showed a mixed pattern of positive changes in primary schools and zero outcomes
      in secondary schools. The findings regarding the effects of external support
      revealed limited outcomes. CONCLUSIONS: The outcomes of the evaluation study
      confirm that a school-based anti-bullying intervention strategy can be effective
      in reducing problems with bullying, especially within primary schools. It was
      argued that the developmental characteristics of secondary school students
      interfered with the programme outcomes. In addition, the findings revealed no
      extra effects of specific training sessions.

PMID- 10900779
TI  - Development of the school organisational health questionnaire: a measure for
      assessing teacher morale and school organisational climate.
AB  - BACKGROUND: A growing body of empirical evidence suggests that organisational
      factors are more important than classroom specific issues in determining teacher
      morale. Accordingly, it is necessary to have available measures that accurately
      assess morale, as well as the organisational factors that are likely to underpin
      the experience of morale. AIM: Three studies were conducted with the aim of
      developing a psychometrically sound questionnaire that could be used to assess
      teacher morale and various dimensions of school organisational climate. SAMPLE: A
      total of 1,520 teachers from 18 primary and 26 secondary schools in the
      Australian state of Victoria agreed to participate in three separate studies (N =
      615, 342 and 563 in Studies 1, 2 and 3, respectively) that were used to develop
      the questionnaire. The demographic profile of the teachers was similar to that
      found in the Department as a whole. METHOD: All teaching staff in the
      participating schools were asked to complete a self-report questionnaire as part
      of the evaluation of an organisational development programme. RESULTS: A series
      of exploratory and confirmatory factor analyses were used to establish the
      questionnaire's factor structure, and correlation analyses were used to examine
      the questionnaire's convergent and discriminant validity. CONCLUSIONS: The three
      studies resulted in the 54-item School Organisational Health Questionnaire that
      measures teacher morale and 11 separate dimensions of school organisational
      climate: appraisal and recognition, curriculum coordination, effective discipline
      policy, excessive work demands, goal congruence, participative decision-making,
      professional growth, professional interaction, role clarity, student orientation,
      and supportive leadership.

PMID- 10900780
TI  - Self-esteem in children: do goal orientations matter?
AB  - BACKGROUND: Although perceived competence has been identified as an essential
      component of global self-esteem, individual differences in the way competence is
      conceptualised have been virtually ignored. Achievement goal theory suggests that
      two conceptions of competence operate in achievement contexts: competence can be
      conceived as capacity or improvement. These two conceptions are embedded within
      two goal orientations, namely task and ego orientation. AIMS: The study examined
      the relationship of goal orientations and perceptions of athletic ability to
      global self-esteem. SAMPLES: Children (N = 907) attending summer sports camps
      participated in the study. METHOD: Children completed the Perception of Success
      Questionnaire and the Self-Esteem Scale and recorded their perceptions of
      normative athletic ability. RESULTS: High task-oriented children reported
      significantly higher self-esteem than low task-oriented children. Among high task
      oriented boys, those with high perceived ability had higher self-esteem. In
      addition, high ego-oriented boys had high self-esteem when they perceived
      themselves as having high ability in relation to their peers. Finally, among low
      task-oriented girls, those with high perceived ability reported higher self
      esteem. CONCLUSIONS: The findings are consistent with the tenets of achievement
      goal theory that success and failure are subjective psychological states. It is
      recommended that different conceptions of competence are considered in the study
      of self-esteem.

PMID- 10900781
TI  - The nature and development of student motivation.
AB  - AIM: The aim of the present series of studies was to investigate what motivates
      undergraduate students and how their motivation changes during their degree
      course. The present research investigated both subject specific and generic
      motivators by asking students what knowledge areas, skills and experiences were
      important to them. SAMPLE: Study 1: 336 prospective and current undergraduate
      psychology students at a university in southern England. Study 2: 57 year one
      psychology students from a university in the north of England. Study 3: 30
      undergraduate psychology students from the university used in Study 1. METHOD:
      The studies used a modified version of the Radford and Holdstock (1993) scale to
      assess students' objectives in taking a degree programme, by rating the
      importance of knowledge areas, skills development and experiences. Study 1 used a
      cross-sectional design comparing responses of student by year of study. Study 2
      compared responses of students in year one in Study 1 to students at a second
      university. Study 3 used a longitudinal design to investigate changes in values
      by year of study. RESULTS: The findings suggest that there are two types of
      students: those who are motivated by the discipline itself and those who are
      motivated by the acquisition of more general skills and experiences. The
      perceived importance of many aspects declines over the three years of the degree,
      and seems especially low in year two. However, some aspects, notably research
      methodology, and some skills and experiences show marked increases in the final
      year. CONCLUSIONS: Current theories of educational motivation need to be extended
      to account for the difference between subject-related and generic motives.

PMID- 10900783
TI  - [Present-day hygienic problems of industrial waste utilization and ways of their
      solution].
AB  - The paper describes the problem in sanitary-safety solid waste removal and
      utilization and gives ways of its solution.

PMID- 10900782
TI  - The importance of music to adolescents.
AB  - AIMS: The study aims to determine the importance of music to adolescents in
      England, and investigates why they listen to and perform music. SAMPLE: A total
      of 2465 adolescents (1149 males; 1266 females; 50 participants did not state
      their sex) between 13 and 14 years of age who were attending Year 9 at one of 22
      secondary schools in the North Staffordshire region of England. METHOD: A
      questionnaire asked participants (a) about their degree of involvement with
      musical activities; (b) to rate the importance of music relative to other
      activities; and (c) to rate the importance of several factors that might
      determine why they and other people of their age and sex might listen to/perform
      pop and classical music. RESULTS: Responses indicated that i) over 50% of
      respondents either played an instrument currently or had played regularly before
      giving up, and the sample listened to music for an average of 2.45 hours per day;
      ii) listening to music was preferred to other indoor activities but not to
      outdoor activities; iii) listening to/playing pop music has different perceived
      benefits to listening to/playing classical music; iv) responses to suggested
      reasons for listening to music could be grouped into three factors; and v)
      responses to suggested reasons for playing music could be grouped into four
      factors. CONCLUSIONS: These results indicate that music is important to
      adolescents, and that this is because it allows them to (a) portray an 'image' to
      the outside world and (b) satisfy their emotional needs.

PMID- 10900784
TI  - [Mercury levels in humans under conditions of environmental pollution by mercury
      containing industrial waste].
AB  - Hygienic monitoring of lead, cadmium, and mercury as environmental pollutants
      should include the analysis of adverse human and environmental effects. The
      hygienic investigations of environmental pollution with gold-mining waste
      involved measurements of Hg in the water, soil, foodstuffs and human biological
      materials. Hg was found in the biological substrata of both industrial workers
      and the general population since they eat the products of animals and plants from
      the polluted area.

PMID- 10900785
TI  - [Levels of cadmium, lead and copper in inhabitants of Tashkent and Tashkent
      region].
AB  - The authors propose a rapid and selective method for inverse volta amperometric
      determination of the levels of cadmium, lead, and copper in blood and hair in
      microgram/kg. The method requires small blood volumes and no expensive
      anticoagulants.

PMID- 10900786
TI  - [Municipal sewage treatment plants as sources of environmental air pollution].
AB  - Municipal sewage works as sources of ambient air pollution were studied.
      Mechanical cleaning catch frames, primary settlers, aero-tanks, and sludge sites
      are the major air pollution sources. The most important air pollutants are
      ammonia and hydrogen sulfide. Their concentrations above the permissible
      concentrations were registered at distances of 300-500 and as far as 500 mm from
      the aeration stations and sludge sites, respectively.

PMID- 10900787
TI  - [The pattern of distribution of polonium-210 in the superficial soil layer in
      Moscow].
AB  - The pattern of distribution of 210Po, 226Ra, 232Th, and 40K was studied in the
      superficial soil layer of Moscow. There was a correlation between the soil levels
      of the natural uranium decay products 210Po and 226Ra. The ratio of specific
      210Po, 226Ra activities was 1.3 +/- 2.6 in the soil samples. There is a close
      correlation between the soil levels of 210Po and its organic substance. The
      specific activities of the natural radionuclides in the Moscow soil were as
      follows: 210Po 30-50 Bk/kg, 226Ra 10-30 Bk/kg, 232Th 10-30 Bk/kg, and 40K 200-400
      Bk/kg. These levels are no greater than those of those of natural radionuclides
      in the Earth's crust.

PMID- 10900789
TI  - [Russian quaternary ammonium compound-based disinfecting agents].

PMID- 10900788
TI  - [Viral pollution of drinking water in industrial towns of Eastern Siberia].
AB  - The drinking water was tested for viruses in the industrial towns of Eastern
      Siberia. The findings suggest that extremely poor provision with good quality
      drinking water is seen in the town of Ust-Ilimsk where there were high levels of
      pathogenic viruses in the water. The high contamination of drinking water with
      hepatitis A virus and rotavirus is a cause of higher incidence of intestinal
      viral infections in the areas under study.

PMID- 10900790
TI  - [New insecticide formulations for controlling domestic pests].

PMID- 10900791
TI  - [Catalytic properties of dust as criteria of its occupational hazards].
AB  - The catalytic properties of fire clay (kaolin) and mullet dusts versus quartz,
      asbestos, and coal ones were studied. Kaolin and mullet were found to have
      different catalytic capacities mainly of forming free radicals. The dust of
      kaolin increased the level of superoxide anion radical and hydrogen peroxide in
      the granulocytic suspension and H2O2/O2 ratio to a lesser extent than that of
      mullet and quartz. Differences in the catalytic capacity of the examined dusts
      confirm the findings from the investigations of their effects on plasma lipid
      peroxidation (LPO). Kaolin and quartz were the least in elevating LPO. As
      compared with kaolin and quartz, the effects of mullet and asbestos were 2.5 and
      6.5 higher, respectively. The substances were different in their genotoxicity.

PMID- 10900792
TI  - [Hygienic aspects of iodine deficiency prevention].

PMID- 10900793
TI  - [Epidemiological hazards of low-temperature food storage].
AB  - Refrigerator food storage lose its preventive value. This is particularly
      associated with the specific features of the pathogens of saprozoonosis which can
      easily adapt to low temperatures and feed deficit. Pseudotuberculosis agents were
      used to show that saprozoonosis pathogens can live and feed in a warm-blood being
      and in the environment. Their biological features require new approaches to
      controlling these infections.

PMID- 10900794
TI  - [Scientific-research activities of the Research Institute of Child and Adolescent
      Hygiene and Health Care in 1993-1998].

PMID- 10900795
TI  - [Present-day child and adolescent hygiene in the light of S.M. Grombakh's works].

PMID- 10900796
TI  - [Scientific bases of a concept of promotion of health of children and
      adolescents].
AB  - The paper outlines theoretical concepts on society-state-individual to reduce
      mortality, morbidity, and disability among children and adolescents and to
      increase physical and social fitness at the stage of human maturation. On
      implementation of the concepts, the author proposed to follow the following
      principles: 1) their governmental nature and priority of preventive measures; 2)
      the structurization of measures by levels (federal, regional); 3) the
      optimization of resources and financing; 4) interdisciplinary integration and
      intersectoral cooperation.

PMID- 10900797
TI  - [Health and self-perception of health status by children during the schooling
      period].

PMID- 10900798
TI  - [Study of the impact of experimental curriculum education on the health status of
      gymnasium students].
AB  - The intensified innovative curriculum at new type schools (gymnasia) has no
      negative impact on pupil's health provided that an educational process is
      correctly designed and there is sufficient motor activity. Traditional health
      indices of a children's collective body, such as physical development, morbidity,
      etc.) are a reliable criterion for the realization of their adaptive capacities
      under the influence of unfavorable environmental factors.

PMID- 10900799
TI  - [Health status of adolescents taught by the school-higher educational
      establishment curriculum].
AB  - The paper deals with problems in teaching adolescents at different levels of
      education (medical lyceum--higher educational establishment (HEE)). Their health
      status, functional changes that can vary with the pattern of training are
      comprehensively assessed. The school-HEE program was found to be effective as the
      high progress of lyceum students causes worse health. The students' high process
      and low morbidity within an academic year is suggestive of their rapid adaptation
      to HEE studies.

PMID- 10900800
TI  - [Problems of healthy life style formation in pupils at educational
      establishments].

PMID- 10900801
TI  - [Health status of children living in the vicinity of coal open pits].
AB  - Open-cast mining in the vicinities of the town of Cheremkhovo is cause of
      environmental pollution with Al, Pb, Zn, Cu, As, B, Ni, Be, Sn, Y, Cr, V.
      Assessing the health status of children living in this area revealed the
      following: a high incidence of diseases; multimorbidity with a tendency for
      chronicity; reduced concentrations of a complex of essential trace elements in
      the children's hair below the physiological level; abundant hair heavy metals;
      the relation of hair trace element composition to the coal output. Micro- and
      macroelement imbalance is likely to cause high morbidity in the children living
      in the open-cast mining area.

PMID- 10900802
TI  - [Methodology of the rationale of setting hygienic standards for disinfectants].

PMID- 10900803
TI  - [Sanitary and toxicological assessment of anticoagulant rodenticides].

PMID- 10900805
TI  - [Use of biologically active properties of marine organisms for correction of
      lipid metabolism in alcoholic intoxication].

PMID- 10900804
TI  - [Anticholinesterase effect of potential organophosphorus synergists of
      pyrethroids].

PMID- 10900806
TI  - [Study of congenital developmental defects as an important element of the social
      hygienic monitoring system].

PMID- 10900807
TI  - [Significance of immunological parameters in hygienic studies].

PMID- 10900808
TI  - [Use of elements of the multidimensional scaling method during social-hygienic
      monitoring].

PMID- 10900809
TI  - Climate quality and climate consensus as mediators of the relationship between
      organizational antecedents and outcomes.
AB  - Research has shown that climate quality (average climate ratings) is related to
      organizational antecedents and outcomes, but researchers have yet to examine
      climate consensus (the variance of climate ratings). Similarly, studies have
      investigated typical behavior (members' average performance), but have neglected
      behavioral similarity (within-group variance). Data from 1,196 members in 180
      organizations were used to test relationships of climate quality and consensus
      with organizational antecedents and outcomes. Climate quality and consensus both
      had significant correlations with organizational antecedents and outcomes, but
      climate consensus did not contribute a significant increment to the prediction of
      organizational outcomes. Finally, quality mediated many relationships between
      organizational antecedents and outcomes.

PMID- 10900810
TI  - Development of a measure of workplace deviance.
AB  - The purpose of this research was to develop broad, theoretically derived
      measure(s) of deviant behavior in the workplace. Two scales were developed: a 12
      item scale of organizational deviance (deviant behaviors directly harmful to the
      organization) and a 7-item scale of interpersonal deviance (deviant behaviors
      directly harmful to other individuals within the organization). These scales were
      found to have internal reliabilities of .81 and .78, respectively. Confirmatory
      factor analysis verified that a 2-factor structure had acceptable fit.
      Preliminary evidence of construct validity is also provided. The implications of
      this instrument for future empirical research on workplace deviance are
      discussed.

PMID- 10900811
TI  - Self-management training for improving job performance: a field experiment
      involving salespeople.
AB  - In a control-group field experiment using a reversal design, 30 insurance
      salespeople were randomly assigned to an experimental group that received self
      management training. A multivariate analysis of variance and subsequent repeated
      measures analyses of variance revealed that, compared with a control condition (n
      = 30), training in self-management skills significantly improved job performance
      as assessed through both objective and subjective measures. Performance
      improvement continued with time, and increases were sustained across a 12-month
      period posttraining. Subsequent training of the control group produced similar
      increases in self-efficacy, outcome expectancies, and job performance. Potential
      mediating effects of self-efficacy and outcome expectancies on the self
      management-performance relationship were explored and partially supported.

PMID- 10900812
TI  - Predictors and outcomes of proactivity in the socialization process.
AB  - This 3-wave longitudinal study aimed to extend current understanding of the
      predictors and outcomes of employee proactivity (involving information seeking,
      feedback seeking, relationship building, and positive framing) in the
      socialization process. Two personality variables, extraversion and openness to
      experience, were associated with higher levels of proactive socialization
      behavior. Of the proactive behaviors studied, feedback seeking and relationship
      building were highlighted in their importance because of their various
      relationships with the work-related outcomes assessed in this study (e.g., social
      integration, role clarity, job satisfaction, intention to turnover, and actual
      turnover). The results also highlighted the importance of 2 control variables
      (opportunity to interact with others on the job and skill level of the new job)
      in the experience of socialization into a new job.

PMID- 10900813
TI  - Remedial self-fulfilling prophecy: two field experiments to prevent Golem effects
      among disadvantaged women.
AB  - The Pygmalion effect is a self-fulfilling prophecy (SFP) in which raising leader
      expectations boosts subordinate performance. Although attempts to produce
      Pygmalion effects have been successful repeatedly among men, attempts to produce
      Pygmalion effects with female leaders have yielded null results. Also, only 1
      experiment has demonstrated the Golem effect (i.e., negative SFP in which low
      leader expectations impair subordinate performance). In 2 field experiments
      testing the SFP hypothesis among women leading disadvantaged women, experimental
      leaders were led to believe that their trainees had higher than usual potential.
      In reality, the trainees had been assigned randomly. Manipulation checks
      confirmed that the treatment raised leader expectations toward experimental
      trainees. Analysis of variance of performance detected the predicted SFP effects
      in both experiments. These were the first-ever experimental confirmations of SFP
      among women as leaders.

PMID- 10900814
TI  - College grade point average as a personnel selection device: ethnic group
      differences and potential adverse impact.
AB  - College grade point average (GPA) is often used in a variety of ways in personnel
      selection. Unfortunately, there is little empirical research literature in human
      resource management that informs researchers or practitioners about the magnitude
      of ethnic group differences and any potential adverse impact implications when
      using cumulative GPA for selection. Data from a medium-sized university in the
      Southeast (N = 7,498) indicate that the standardized average Black-White
      difference for cumulative GPA in the senior year is d = 0.78. The authors also
      conducted analyses at 3 GPA screens (3.00, 3.25, and 3.50) to demonstrate that
      employers (or educators) might face adverse impact at all 3 levels if GPA
      continues to be implemented as part of a selection system. Implications and
      future research are discussed.

PMID- 10900815
TI  - An examination of the mediating role of psychological empowerment on the
      relations between the job, interpersonal relationships, and work outcomes.
AB  - A field investigation of 337 employees and their immediate superiors tested the
      mediating role of empowerment in relations between job characteristics, leader
      member exchange (LMX), team-member exchange (TMX), and work outcomes. The meaning
      and competence dimensions of empowerment mediated the relation between job
      characteristics and work satisfaction. The meaning dimension also mediated the
      relation between job characteristics and organizational commitment. Contrary to
      prediction, empowerment did not mediate relations between LMX, TMX, and the
      outcome variables. Rather, LMX and TMX were directly related to organizational
      commitment. In addition, TMX was directly related to job performance. These
      findings suggest that work satisfaction is explained largely by job
      characteristics (through empowerment) but that LMX and TMX combine with job
      characteristics and empowerment to explain variation in organizational commitment
      and job performance.

PMID- 10900816
TI  - The temporal factor of change in stressor-strain relationships: a growth curve
      model on a longitudinal study in east Germany.
AB  - Several theoretical models describing how stressor-strain relationships unfold in
      time (e.g., M. Frese & D. Zapf, 1988) were tested with a longitudinal study, with
      6 measurement waves, using multivariate latent growth curve models. The latent
      growth curve model made it possible to decompose trait and state components of
      strains and to show that both trait and state components are affected by work
      stressors. Because East Germany constitutes a high-change environment, it is an
      appropriate setting in which to study the relationship between work stressors and
      strains. The results showed that both the state and trait components of strains
      were affected by stressors. For example, individual trends in uncertainty
      (stressor) and worrying (strain) were related, whereas worrying also showed a
      short-term relationship with time pressure (another stressor). In particular, the
      decomposition into trait and state components was only possible with the growth
      curve method that was used.

PMID- 10900817
TI  - An examination of organizational and team commitment in a self-directed team
      environment.
AB  - A model hypothesizing differential relationships among predictor variables and
      individual commitment to the organization and work team was tested. Data from 485
      members of sewing teams supported the existence of differential relationships
      between predictors and organizational and team commitment. In particular,
      intersender conflict and satisfaction with coworkers were more strongly related
      to team commitment than to organizational commitment. Resource-related conflict
      and satisfaction with supervision were more strongly related to organizational
      commitment than to team commitment. Perceived task interdependence was strongly
      related to both commitment foci. Contrary to prediction, the relationships
      between perceived task interdependence and the 2 commitment foci were not
      significantly different. Relationships with antecedent variables help explain how
      differential levels of commitment to the 2 foci may be formed. Indirect effects
      of exogenous variables are reported.

PMID- 10900818
TI  - Assessing differential functioning in a satisfaction scale.
AB  - In this study, an item response theory-based differential functioning of items
      and tests (DFIT) framework (N. S. Raju, W. J. van der Linden, & P. F. Fleer,
      1995) was applied to a Likert-type scale. Several differential item functioning
      (DIF) analyses compared the item characteristics of a 10-item satisfaction scale
      for Black and White examinees and for female and male examinees. F. M. Lord's
      (1980) chi-square and the extended signed area (SA) measures were also used. The
      results showed that the DFIT indices consistently performed in the expected
      manner. The results from Lord's chi-square and the SA procedures were somewhat
      varied across comparisons. A discussion of these results along with an
      illustration of an item with significant DIF and suggestions for future DIF
      research are presented.

PMID- 10900819
TI  - Procedures: do we really want to know them? An examination of the effects of
      procedural justice on self-esteem.
AB  - This study examined the effects of procedural justice on state-dependent self
      esteem using the group-value model and attribution theory to present competing
      theoretical perspectives. The group-value model predicts a positive relationship
      between self-esteem and fair procedures. In contrast, attribution theory suggests
      procedural fairness interacts with outcome favorability to influence self-esteem.
      Thus, fair procedures will result in higher self-esteem ratings than unfair
      procedures when the outcome is positive but will result in lower self-esteem
      ratings than unfair procedures when the outcome is negative. The results of a
      laboratory and field study provide converging evidence to support the attribution
      theory predictions. The results of a 2nd laboratory study suggest that self
      esteem is influenced by outcome expectancies, not actual outcomes.

PMID- 10900820
TI  - Perceptions of organizational politics as a moderator of the relationship between
      conscientiousness and job performance.
AB  - Meta-analytic studies of the relationships between the five-factor model of
      personality constructs and job performance indicate that conscientiousness has
      been the most consistent predictor. Recent research has sought to identify
      situational factors that may explain additional variance beyond what has been
      reported by simple bivariate relationships. The authors hypothesized that
      perceptions of organizational politics would moderate the relationship between
      conscientiousness and job performance. Data collected from 234 male and 579
      female workers in 4 organizations indicated that conscientiousness was related to
      job performance among workers perceiving average to high levels of organizational
      politics but unrelated to performance among workers perceiving low levels of
      organizational politics. Moreover, perceptions of organizational politics were
      negatively related to job performance only among workers of average to low levels
      of conscientiousness.

PMID- 10900821
TI  - Job context, selection decision outcome, and the perceived fairness of selection
      tests: biodata as an illustrative case.
AB  - S. W. Gilliland (1993) has proposed a model of perceived selection system
      fairness to help understand applicants' prehire and posthire behavior. The
      present study aimed to verify and extend his framework by investigating the role
      of job context in the formation of fairness perceptions of biodata. A sample of
      255 students (108 men, 147 women) completed an operational biodata instrument,
      believing that it would be used to hire persons for either international, local,
      or unspecified entry-level managerial positions. Participants were then presented
      with outcome information (selected or rejected for further consideration).
      Consistent support was found for the research hypotheses derived from the
      Gilliland model. Participants' perceptions of the fairness and job relatedness of
      biodata were affected by the selection context and decision outcome. The
      importance of considering selection context in assessments of perceived test
      fairness is discussed.

PMID- 10900822
TI  - Use of innovative methods in the eradication of bovine tuberculosis.
AB  - During final phases of eradication programmes, strains of Mycobacterium sp. not
      belonging to the tuberculosis complex increase their relative frequency and are
      responsible for positive skin test reactions. Moreover, the specificity of any
      indirect diagnostic test, such as the skin test, is never completely accurate,
      therefore even when tuberculosis infection is completely eradicated, a number of
      false positive reactions are to be expected. The aim of this paper is to evaluate
      the performances of traditional isolation/typing techniques, automatic
      isolation/typing techniques based on fluorimetric detection of bacterial growth
      (Bactec), skin tests and the -interferon test. Samples examined for the
      evaluation of test sensitivities originated from 154 infected animals belonging
      to 32 infected herds. Samples used as negative controls in the evaluation of test
      specificities originated from 86 animals of nine officially infection-free herds.
      The automatic isolation/typing technique based on fluorimetric detection of
      bacterial growth showed higher sensitivity than the traditional isolation typing
      technique. Moreover, it allowed a safer processing of bacterial cultures,
      decreasing the risk for laboratory workers. The observed performance of the gamma
      interferon test was considered beneficial in that it increased the sensitivity of
      individual diagnosis within an infected herd, especially in 'problem herds', but
      its poor specificity did not improve detection of infected herds compared to the
      skin test.

PMID- 10900823
TI  - In vitro susceptibility of Escherichia coli strains isolated from diarrhoeic
      dairy calves to 15 antimicrobial agents.
AB  - The in vitro activities of 15 antimicrobial agents against 195 strains of
      Escherichia coli isolated from dairy calves affected by neonatal diarrhoea were
      determined. Of these strains 137 produced one or more potential virulence factors
      (F5, F41, F17, cytotoxic necrotizing factor, verotoxin and the eae gene), but the
      remaining 58 strains did not produce any of these factors. The overall percentage
      of resistant strains to streptomycin, tylosin and tetracycline was very high
      (above 65%). A high level of resistance (from 23 to 50%) to ampicillin, neomycin,
      kanamycin, spectinomycin, chloramphenicol, sulphadimethoxine and trimethoprim was
      also detected. The E. coli strains were very susceptible (89-95%) to apramycin
      and gentamicin and highly susceptible (99-100%) to polymyxin B, florfenicol and
      nitrofurazone. Some significant differences (P < 0.05) in the frequencies of
      resistance to some of the antimicrobials tested and in the rates of multi-drug
      resistance among the strains producing potential virulence factors and non
      fimbriated, non-toxigenic, eae-negative strains were found. Most of the strains
      showed multi-resistance: 76.9% of the isolates were resistant to at least two
      antibiotics, 67.7% were resistant to at least four antibiotics and 50.3% were
      resistant to at least six antibiotics.

PMID- 10900824
TI  - Detection of Mycobacterium tuberculosis complex in lymph nodes of wild boar (Sus
      scrofa) by a target-amplified test system.
AB  - A detailed macroscopic and histological description is given of tuberculous-like
      lesions in mandibular lymph nodes obtained from wild boar (Sus scrofa) collected
      in Italy during the 1995/1996 hunting season, as well as a correlation with
      results obtained from a Mycobacterium tuberculosis complex target amplified test
      system. According to macroscopic appearance, lesions were largely represented by
      caseous-necrotic-calcified granulomata (n = 272/285; 95.4%), while histological
      investigations showed mainly necrotic-calcified (n = 82/218; 37.6%) and
      fibronecrotic-calcified (n = 81/218; 37.2%) lesions. When tested with a target
      rRNA amplification/hybridization technique to detect M. tuberculosis complex, 112
      (43.6%) samples out of 275 tested gave positive results.

PMID- 10900825
TI  - Dynamics of the development of Chlamydophila psittaci inclusions in epithelial
      and fibroblast host cells.
AB  - The development of Chlamydophila psittaci (formerly Chlamydia psittaci, avian
      strains) inclusions in fibroblast L-929 and epithelial BGM cell lines was studied
      along the bacterial growth cycle using a BGM cell-adapted strain in the presence
      or absence of cycloheximide and cycloheximide + polyethylene glycol. Evolution of
      the inclusions was determined in terms of their number and size at 24, 30, 36, 48
      and 54 h after infection. Significant differences in the chlamydial growth were
      found between both host cells, throughout the study. Higher numbers of inclusions
      (P < 0.05) were observed in L cells while larger inclusions (P < 0.01) were found
      in BGM cells. In both fibroblast and epithelial cells, inclusions showed a
      significant (P < 0.001) increase in size at the later times studied. Free
      extracellular chlamydial particles were noticed at 48 and 54 h post-infection
      (p.i.) in infected L cells, and at 54 h p.i. in BGM cells. Addition of
      cycloheximide or cycloheximide + polyethylene glycol had no significant effect on
      the number of inclusions or their size. The results suggest that host cell
      characteristics and innate compatibility between Chlamydophila strain and host
      cell are more important than host cell adaptation for the development of the
      microorganism.

PMID- 10900826
TI  - Development of a differential multiplex PCR assay for equine herpesvirus 1 and 4
      as a diagnostic tool.
AB  - In this study, a multiplex polymerase chain reaction (PCR) procedure was
      developed for differentiation of strains and field isolates of equine herpesvirus
      type 1 (EHV-1) and type 4 (EHV-4). Specific oli-gonucleotide primers were
      combined to amplify the thymidine kinase (TK) gene region of EHV-1 and EHV-4,
      which would yield fragments of different lengths for each virus in the same
      amplification reaction. The specificity of the largest PCR amplicon for EHV-4 was
      confirmed by restriction digestion with HindIII. The multiplex PCR proved to be a
      fast and sensitive method for typing EHV-1 and EHV-4 isolates and for detection
      and differentiation of both viruses in field samples in which infectious virus is
      no longer available. The sensitivity was improved by combining cycling
      optimization and visualization of PCR products in ethidium bromide and silver
      stained acrylamide gels.

PMID- 10900827
TI  - A nucleotide deletion causing a translational stop in the protease reading frame
      of bovine leukaemia virus (BLV) results in modified protein expression and loss
      of infectivity.
AB  - Bovine leukaemia virus (BLV) is an oncogenic retrovirus that causes B-cell
      lymphocytosis and in the terminal stage of the disease lymphosarcoma. The
      comparison of the previously published BLV provirus sequence from Belgium,
      Australia and Japan showed that the protease gene (prt) of the Australian and the
      Japanese isolate contain a nucleotide deletion when compared to the Belgian
      isolate. Because all these proviruses were isolated from tumour tissue, the prt
      gene of functionally active and infectious proviruses from peripheral blood
      leucocytes (PBLs) of BLV-infected cattle and from BLV-infected fetal lamb kidney
      cells were sequenced. The only variations between these sequences and the Belgian
      isolate consist of nucleotide substitutions. The delection of one nucleotide of
      the prt gene of the Japanese and the Australian BLV tumour isolate caused a
      changed reading frame and a premature translational stop. It was shown that the
      Japanese provirus is non-infectious in transfected cell culture and in injected
      sheep. To analyse the impact of the prt mutation on viral protein expression and
      infectivity, the prt region of the Japanese provirus was exchanged with the prt
      region from the Belgian provirus. The resulting pBLVprtbelg was infectious in
      transfected cells and enabled the expression of gag and gag-precursor proteins.
      One sheep was injected with this mutated provirus and became positive in BLV-PCR,
      but no seroconversion was developed. The prt mutation of the Japanese tumour
      isolates was shown to be responsible for the loss of infectivity and changed
      viral expression. These results and the occurrence of this mutation in only two
      isolates from lymphosarcoma indicate a possible relation between the prt mutation
      and the induction of cell transformation.

PMID- 10900828
TI  - Studies on the modulation of leucocyte subpopulations and immunoglobulins
      following intramammary infusion of beta 1,3-glucan into the bovine udder during
      the dry period.
AB  - Inflammatory and immunological reactions after intramammary infusion of beta 1,3
      glucan were studied during the steady dry period and involution phase of the
      bovine udder. The effects of a single intramammary infusion of two different
      doses (100 and 200 mg) of beta 1,3-glucan were evaluated during the steady dry
      period. In a second study, the effects of beta 1,3-glucan at drying off were
      studied by using two treatment regimens; a single infusion at drying off,
      compared with two infusions of the compound, at drying off and again 2 weeks
      later. Total and differential leucocyte counts were measured in both blood and
      udder secretions. Additionally, the expression of receptors for CD14 and MHC
      class II on leucocytes, and the expression of receptors for CD4, CD8, WC1, IL2R
      and B-cells on lymphocytes was measured in mammary secretions by flow cytometric
      analyses. The concentrations of immunoglobulins in udder secretions were measured
      by radial immunodiffusion. The results showed that a single intramammary infusion
      of beta 1,3-glucan during the steady dry period causes transient enhancement of
      some aspects of the inflammatory and immune responses. The increases in somatic
      cell counts, numbers of monocytes/macrophages, and in proportions of CD14+ and
      MHC class II+ leucocytes in udder secretions were dose-dependent. Infusion of
      beta 1,3-glucan also slightly increased the proportion of CD4+ lymphocytes and
      the concentrations of IgG1 and IgG2 in dry secretions. Infusion of beta 1,3
      glucan at drying off seemed to accelerate the involution process through an
      increase in somatic cells, particularly in the numbers of macrophages, in mammary
      secretions. The numbers of lymphocytes and polymorphonuclear leucocytes, the
      proportions of IL2R+ lymphocytes, the proportions of CD14+ or MHC class II+
      leucocytes and the concentrations of IgG1 and IgG2 also increased in comparison
      with untreated controls. Moreover, a second infusion of beta 1,3-glucan tended to
      prolong this response, indicating that this might be an effective means of
      enhancing the mammary defence against udder infections closer to calving. In
      conclusion, the results indicate the intramammary infusion of beta 1,3-glucan
      could be used to enhance the defence mechanisms of the bovine udder against
      infections, especially during early involution.

PMID- 10900829
TI  - Production and characterization of monoclonal antibodies against bovine leukaemia
      virus using various crude antigen preparations: a comparative study.
AB  - A total of 59 monoclonal antibodies (mAbs) specific against the bovine leukaemia
      virus (BLV) using different antigen preparations was produced. The five antigen
      preparations for immunizing BALB/c mice were: live cells (CEL), sonicated and
      ultracentrifuged cells (SOC), cell lysates (LYS), semi-purified BLV (PV), and
      formalin-treated cells (FOR) from two cell lines permanently infected with BLV
      (FLK-BLV and BLV-bat2). These viral component presentations were selected to
      obtain mAbs against specific BLV proteins: located on the cell surface (FOR and
      CEL), in free virus particles (PV) and intracellular viral proteins (SOC and
      LYS). Two antigen preparations (SOC and LYS) were lethal to the mice following
      the intravenous and intrasplenic routes. Six fusions were performed in this study
      that rendered specific antibodies against BLV. The highest number of hybridomas
      was produced with SOC; however, the majority of the hybridomas produced (> 90%)
      were against cellular proteins. Even though immunization with PV gave the lowest
      number of hybridomas, the majority of them were specific against BLV. Based on
      the reactivity of the mAbs in Western blot (WB), we classified the mAbs into five
      groups, namely anti-gp51SU (39 mAbs), anti-gp30TM (six mAbs), anti-Pr72env (nine
      mAbs), anti-Pr66gag-pro (one mAb) and anti-Prgag (four mAbs). A very high
      percentage of the mAbs produced (48 of 59) reacted with gp51SU, suggesting that
      this is the most immunogenic and accessible BLV protein presented in the
      different antigen preparations. The majority of our mAbs recognized more than one
      band in WB, suggesting that, aside from reacting with mature proteins, the mAbs
      also recognized viral precursors.

PMID- 10900830
TI  - Telomeres and telomerase.

PMID- 10900831
TI  - Advanced applications of MRI in human brain science.
AB  - Magnetic resonance imaging of the brain is now generally indispensable to state
      of art clinical medicine. Robust, high resolution imaging systems are currently
      available worldwide. The availability of MRI has, in little more than a decade,
      revolutionized the certainty and efficiency of clinical diagnosis and management.
      As a dividend of this revolution, clinicians and radiologists who are expert in
      the many and varied applications of MRI methods are able to relate this expertise
      to a confident mastery of the topographic anatomy of the brain as revealed in
      magnetic resonance images. Whereas the yield to clinical objectives has been
      massive, the clinician as yet draws upon a relatively limited sampling of the
      potential informational harvest from this technology which in theory could
      further enrich both clinical concerns and those of fundamental neuroscience. Here
      we will review early explorations into these other offerings with the expectation
      that the coming decade will see them established comfortably with current uses.
      We will also consider potential offerings of the extended applications of brain
      MRI to the characterization and insights into biological origins of certain
      obscure developmental disorders.

PMID- 10900832
TI  - Diagnostic value of a bedside test for cardiac troponin T in the patient with
      chest pain presenting to the emergency room.
AB  - Identification of patients with acute chest pain due to acute coronary syndrome
      is a common and difficult challenge for emergency physicians. A prospective study
      was conducted to assess the diagnostic value of a bedside test of cardiac
      troponin T in the emergency room setting. Forty-nine consecutive patients, who
      visited the emergency room within 6 hours of the onset of acute chest pain, were
      enrolled. Of the 26 patients who were ultimately diagnosed as having acute
      coronary syndrome, seven patients (27%) had positive cardiac troponin T assay
      results, whereas none of the patients without acute coronary syndrome had
      positive results (0%). For patients with acute coronary syndrome who presented
      later than 3 hours after the onset (n = 4), the test was positive in all cases
      (positive predictive value: 100%, negative predictive value: 100%, p < 0.01).
      However, the positive rate was only 14% for those who presented earlier than 3
      hours after the onset (n = 22) (positive predictive value: 100%, negative
      predictive value: 47%, p = 0.84). In conclusion, bedside troponin T test results
      should be evaluated considering the time interval from the onset of chest
      symptoms.

PMID- 10900833
TI  - Seeing through the stratum corneum.
AB  - The stratum corneum (SC) provides a vital barrier membrane between the external
      environment and the vulnerable internal tissues of the skin. It impedes the flow
      of water, the penetration of xenobiotics, and invasion of pathogenic micro
      organisms. It also has protective capacity against ultraviolet radiation and
      thermal injury. As routine histopathology provides a misleading picture of a
      disorganized and shadowy SC, we would recommend the skin surface biopsy
      technique. This painless technique is easy and reliable in obtaining information
      from the SC. It demonstrates the geometric patterns of the surface, the openings
      of the eccrine ducts and hair follicles. The skin surface biopsy technique is
      also ideal for the investigation of the in situ microbiology of skin. Staining
      with periodic acid Schiff reagent makes it possible to see ringworm fungi,
      pityriasis versicolor, candida species, or erythrasma micro-organisms. Scanning
      electron microscopy can be employed when the higher magnification is needed.
      Histochemical applications include silver staining for melanin particle,
      potassium ferricyanide staining for blood pigments and lipid staining with Sudan
      red, for sebum. The rate of movement of topically applied drugs into the skin can
      be measured using the skin surface biopsy technique. The concentration of
      radiolabelled drugs can be counted and compared. Comedogenicity and DNA analysis
      are other applications of this non-invasive technique.

PMID- 10900834
TI  - [Extended gastropancreatoduodenal resection (GPDR)].
AB  - The authors for the first time in Russia have begun serial performance of the
      extended GPDR. The operations were accompanied by careful morphological
      investigations of the removed organs and tissues. It was established that in all
      patients with exocrine cancer of head of the pancreas the tumor growth extended
      the region of the regional lymph nodes, i.e. standard GPDR in these patients
      oncologically could not be considered as adequate operation. Further performance
      of GPDR for pancreatic head exocrine cancer will expand knowledge about
      metastatic spread and will open opportunities to improve long-term survival of
      the patients with exocrine cancer of the head of the pancreas.

PMID- 10900835
TI  - [Immunogenetic aspects in pathogenesis of acute pancreatitis].
AB  - Acute pancreatitis is characterized by essential decrease of the activity of the
      complement C1-C5 system components which is more marked under destructive form of
      the disease. The increased consumption of the components of the complement may be
      determined by forming immune complexes under interaction of the antibodies with
      structural and secretory components of the pancreas and direct proteolytic
      conversion under influence of trypsin. The revealed associations with HLA I
      antigens suggest the presence of genetic determination of the changes in the
      complement system. It may be also possible that components of the complement
      system, in particular C4 which is immune product of the HLA class III region,
      exert regulating influence on humoral immune reactions in acute pancreatitis.

PMID- 10900836
TI  - [Puncture-drainage treatment of pancreatic postnecrotic pseudocysts].
AB  - From 1989 to 1998 we treated 94 patients with pancreatic pseudocysts. 55 patients
      underwent laparotomy (external drainage of the cyst, sequestrectomy). 14.5%
      patients of this group presented with postoperative complications, mean hospital
      stay was 36 days. During 1997-1998 we performed US-controlled punctures and
      drainage in 37 patients with pancreatic pseudocysts. This method was efficient in
      83.7% of the cases without sequesters in the cystic cavity. Use of this method
      allowed to decrease the percentage of complications and lethality rate, and
      reduce the mean hospital stay by 47.2%.

PMID- 10900838
TI  - [Non-strain methods of hernioplasty in the treatment of postoperative ventral
      hernias].
AB  - In the last 2 years we performed 26 nonstrain hernioplasties for postoperative
      ventral hernias (16 laparoscopic and 10 open operations). Indications for
      laparoscopic operation were hernias after "primary" laparotomy, multiple
      aponeurosis defects, and also demand of simultaneous operations. We preferred
      open plastics in recurrent hernias, repeated abdominal operations, laparoscopic
      hernioplasty impossibility revealed during the operation. Fast rehabilitation and
      their early return to work are advantages of nonstrain hernioplasty. Mean
      hospital stay was 7.5 days with a general disability of 22.3 days. We believe
      that open hernioplasty is most simple and reliable. As to laparoscopic
      hernioplasty, we think it less reliable.

PMID- 10900837
TI  - [Embolization of splenic artery in children with portal hypertension].
AB  - This study examined the results of embolization of the splenic artery (ESA) in 30
      children (age ranged from 5 to 14 years) with portal hypertension. Effectiveness
      of ESA was evaluated by a decrease in spleen size, hypersplenism, disappearance
      of esophageal varices and improvement in blood count. The results show that
      chronic embolization of the splenic artery in children is relatively safe and
      effective surgical treatment for portal hypertension. It lessens portal
      hypertension, reduces and in some cases eliminates hypersplenism and
      splenomegaly. Furthermore, being pathogenically sound it may be operation of
      choice in treatment of chronic hepatitis with portal hypertension and is well
      tolerated by children.

PMID- 10900839
TI  - [Autodermal plastics and transposition of musculus rectus abdominus for giant
      postoperative hernias].
AB  - For reduction of postoperative hernia relapses rate the technique of the
      autodermal plastics and transposition of musculus rectus abdominalis (MRA) was
      developed. This technique consists of two-sided transection of the lateral
      abdominal muscles (oblique and transverse) on the pararectal line, transposition
      of MRA together with their sheaths medially by autodermal continuous lacing to
      complete adaptation of the edges. Closing of the lateral muscle-aponeurotic
      defects was carried out with use of the double autodermal grafts which were
      prepared by Yanov's technique. This technique is indicated for giant
      postoperative hernias and pronounced diastase of the MRA in people with well
      developed abdominal muscles. This technique was used in 11 patients without
      complications after surgery. Long-term results are available for all the
      patients. The relapses were absent. The technique, developed by us, provides
      first of all restoration of physiological function of the MRA, and also closing
      of the abdominal wall muscle-aponeurotic defect.

PMID- 10900840
TI  - [Transesophageal gastrostomy].
AB  - For gastrostomy after thoracic esophagus extirpation its distal stump was used.
      It is confirmed, that transesophageal gastrostomy has a number of advantages.
      Pezzer's catheter can be used as gastrostomic tube which self-fixes in given
      position and secures reliable gastrostoma sealing. Suturing of the stomach to
      parietal peritoneum around gastrostoma is not more necessary. Deformation and
      reduction of the stomach size are excluded and stomach is kept ready for
      subsequent plastic replacement of the oesophagus. The operation gets
      oncologically more radical as a result of removal of paraesophageal cellular fat
      and potentially metastatic lymph nodes during mobilization of the oesophagus and
      cardia distal stump. The routine technique of transesophageal gastrostomy is
      described. This technique is applied in 17 patients. Complications were not
      registered.

PMID- 10900841
TI  - [Laparoscopic appendectomy in pediatric patients: experience of 2300 operations].
AB  - The experience of 2300 laparoscopic appendectomies in children aged between 7
      days and 14 years is presented. Uncomplicated forms of acute appendicitis were
      observed in 1611 patients (70.1%). Complicated forms were observed in 689 (29.9%)
      patients: general peritonitis in 196, local peritonitis--in 334, periappendicular
      abscess--in 122 and friable infiltrate--in 37 patients. Laparoscopic appendectomy
      according to F. Gotz modified and adapted by us to children's age was used for
      all variants of the appendix location, including atypical. Optimal surgical
      approaches for children of early age and children over 3 years were developed.
      All laparoscopic interventions were completed endosurgically. Only in 15 (0.65%)
      patients the transition to open surgical operation was carried out on a
      diagnostic phase of the laparoscopic appendectomy for contraindications (solid
      infiltration, general peritonitis with multiple abscesses, intestine paresis with
      need of decompression). On comparative estimation of the laparoscopic and
      traditional appendectomies the indisputable advantages of the endoscopic
      technique are proved: more smooth course of the postoperative period, reduction
      of complications' number, reduction of hospital stay. Laparoscopic appendectomy
      is the most effective technique for the treatment of acute appendicitis
      complicated forms. Mean operative time was 65 min (range 42-120 min). Total
      amount of the postoperative complications in this group decreased almost 3 times.
      Frequency of such serious intraabdominal complications as acute commissural ileus
      decreased 3.5 times, infiltrates and abscesses of the abdominal cavity--2 times.
      Suppuration of the anterior abdominal wall was extremely rare. Mean hospital stay
      reduced almost 2 times. Intraoperative complications and lethality was not
      observed.

PMID- 10900842
TI  - [Surgical treatment of extraperitoneal rectal and perineal injuries].
AB  - The aim of this study was to analyse the results of the treatment of
      extraperitoneal rectal and perineal injuries for 153 patients. All the patients
      were examined according to the scheme. Therapeutic-diagnostic algorithm was
      developed for perineal, anal, rectal injuries. Wide opening and drainage of the
      wound was used. The method allows to avoid colostomy and its subsequent operative
      closing in extraperitoneal injury of the rectum. The method of surgical treatment
      is recommended in extraperitoneal rectal and perineal injuries.

PMID- 10900844
TI  - [Famotidin (quamatel) in the treatment of gastroduodenal ulcer].

PMID- 10900843
TI  - [Short- and long-term results of sphincter preserving operations with creation of
      colonic J-reservoir].
AB  - The aim of this study was to evaluate short- and long-term results of sphincter
      preserving operations with forming a colonic J-reservoir. This study examined the
      results of the treatment of 63 patients with medioampullary carcinoma of the
      rectum. Sphincter preserving operations with forming a reservoiroanal anastomosis
      were made in 34 patients (test group), 29 patients had sphincter preserving
      operations with forming coloanal and supraanal colorectal anastomoses (control
      group). In the test group complications were observed in 6 (17.6%) patients and
      in the control group in 6 (20.7%) patients (p = 0.3962). The defecation frequency
      in the test group 3 months after the operation was 1.87 +/- (1-3) time a day, in
      the control group even through 12 months--3.0 +/- 1.5 times a day (p = 0.0001).
      In terms up to 6 months tenesmus, imperative desire to defecate and defecation's
      multistage more often disturbed the patients of the control group (p = 0.0005).
      The function of the faeces continence was satisfactory in both the patients'
      groups, however in the control group the events of the anal incontinence of I-II
      degree (p > 0.05) occurred more often. The negative aspect of the colonic
      reservoir's forming is frequent change of the evacuation function with
      constipation, however, the differences were statistically insignificant (p >
      0.05). Creation of a colonic reservoir doesn't increase lethality and
      postoperative complications rate, allows to reduce clinical manifestations of a
      "low anterior resection" syndrome.

PMID- 10900845
TI  - [Giant carcinoid tumor of stomach (case report)].

PMID- 10900846
TI  - Perforative duodenal ulcer in incarcerated umbilical hernia.

PMID- 10900848
TI  - [Effect of Helycobacter pylori infection upon the results of peptic ulcer
      surgical treatment].

PMID- 10900847
TI  - [Perforation of esophagus complicated by purulent mediastinitis and pleural
      empyema].

PMID- 10900849
TI  - [Rectal foreign bodies].

PMID- 10900850
TI  - [Professor Pol A.I].

PMID- 10900851
TI  - [Alpha2-macroglobulin: state of the art (review of literature)].

PMID- 10900852
TI  - [Insufficiency and imbalance of the corticoid system as risk factors of
      infertility and ovarian dysfunction].

PMID- 10900854
TI  - [Measurements of salivary lysozyme activity].
AB  - A new method for measuring salivary lysozyme is proposed, which is based on
      lysozyme capacity to lyze glycosaminoglycanes and proteoglycanes in plasma
      membranes of Micrococcus lysodeikticus. Specific activity of the enzyme is
      identified from the amount of protein in glycosaminoglycanes and proteoglycanes.
      The quantity of glycosaminoglycanes and proteoglycanes containing 0.001 mg
      protein/ml/min is suggested to be takes as a unit of lysozyme.

PMID- 10900853
TI  - [Parameters of lipid metabolism during perimenopause and thyroid pathology].
AB  - A total of 210 perimenopausal women were examined. Lipid status was evaluated in
      groups of patients differing by thyroid function and characteristics of the
      perimenopausal period. Case histories were analyzed using a universal information
      chart. Serum levels of T3, T4, TTH, LH, FSH, PRL, E2, and progesterone were
      radioimmunoassayed. Blood lipid spectrum was evaluated on a Kone device (Finland)
      by special standard methods. High levels of cholesterol and triglycerides, a
      tendency to an increase in CH-LDL and CH-VLDL, a decrease in CH-HDL, and a high
      atherogenicity coefficient were detected in women with endemic goiter and
      hypothyrosis in comparison with perimenopausal women without thyroid disease. The
      highest levels of cholesterol, triglycerides, CH-LDL, and atherogenicity
      coefficient were detected in women with endemic goiter and climacteric syndrome,
      which suggests that hypothyrosis in the presence of climacteric syndrome
      aggravates disordered lipid metabolism.

PMID- 10900855
TI  - [Electrolyte homeostasis in petroleum industry workers].
AB  - Disorders in electrolyte balance of erythrocytes and plasma in petroleum industry
      workers are described. All examinees were divided into 3 groups with different
      intensity of chemical exposure: 1) workers of the plant without contacts with
      chemicals (21); 2) workers handling chemicals 2-3 times a week (28)--risk group;
      and 3) workers permanently exposed to chemicals for 3-5 years (46); control group
      consisted of 40 healthy subjects without occupational exposure to chemicals.
      Significant changes in erythrocyte and plasma electrolytes were detected in
      groups 2 and, more so, 3: erythrocyte K, Mg, and Ca levels were decreased and Na
      and P levels increased, while in the plasma K, Mg, and P concentrations were
      increased and Na and Ca decreased.

PMID- 10900856
TI  - [Diagnostic significance of investigation of morphological structures forming
      during a vacuum drying of blood serum from patients with immune pathology].
AB  - In vitro models of vacuum-dried serum of patients with immune diseases are
      presented for the first time. These structures allow visual evaluation of
      transfer of many-step metabolic reactions into certain morphological types.
      Variety and depth of uncontrolled antibody production leave their "structural
      trace" in various diseases. The detected serum morphotype markers can be used for
      early diagnosis of immune conflicts.

PMID- 10900857
TI  - [Characterization of peripheral erythron component in patients with localized
      thermal burns].
AB  - Cytospectrophotometry and electron microscopy of peripheral blood erythrocytes in
      patients with local surface thermal burns and healthy volunteers showed a notable
      decrease in the levels of sulfhydryl groups and lipoproteins, decreased number of
      biconcave discocytes, and increased number of transitional, prehemolytical, and
      degenerative forms of red blood cells. These changes were more pronounced during
      the early posttraumatic period and persisted for 2 months after burns were
      inflicted. Deep structural metabolic and morphological disorganization of the
      erythron peripheral component is a factor of risk of postburn complications.

PMID- 10900858
TI  - [Quality of laboratory studies and modern approaches to its evaluation
      (lecture)].

PMID- 10900859
TI  - [Possibility of using microbiological data in epidemiological analysis of
      hospital pneumonias].
AB  - A total of 528 patients with nosocomial pneumonias were examined by
      bacteriological methods during 4 years. The data on the patients and on 2468
      bacterial strains isolated from them were computer processed using original
      software "Hospital Infection". Special attention was paid to hospital strains of
      pneumonia agents of the same taxonomic position with identical markers of
      antibacterial resistance. Tendencies and seasonal fluctuations in the prevalence
      of hospital serovars were detected. Special bacteriological studies helped detect
      differences in the translocation capacity of different biological variants of the
      agents. Routine bacteriological studies and their adequate statistical computer
      processing yield information needed for epidemiological analysis of the
      development of nosocomial pneumonias in patients of clinical wards of different
      profile.

PMID- 10900861
TI  - [Syndrome of chronic duodenal ileus].

PMID- 10900860
TI  - [Development and approbation of polymerase chain reaction for detection of
      pathogen in Listeria infection].
AB  - A system of primers for detection of Listeria by polymerase chain reaction (PCR)
      has been developed. Specificity and sensitivity of the method was evaluated by
      analyses of reference clinical and abiotic samples. Clinical trials of PCR were
      carried by detecting latent (asymptomatic) carriers of Listeria among healthy
      women of epidemiologically significant professions. PCR is characterized by
      numerous advantages in comparison with the traditional bacteriological analysis.

PMID- 10900862
TI  - [Characteristic features of white matter lesion in elderly with arterial
      hypertension].

PMID- 10900863
TI  - [Psychotherapy impact on effectiveness of in-hospital physical rehabilitation in
      patients with acute coronary syndrome].
AB  - Of 103 patients with acute coronary syndrome (mean age 51.6 +/- 0.9 years) 47
      patients participated in 5 group psychotherapeutic sessions added to conversional
      rehabilitation program. Psychotherapy included progressive muscular relaxation,
      neurolinguistic programming, eriksonian hypnosis, therapeutic metaphora.
      Psychotherapy decreased the hear rate, number of ventricular extrasystoles,
      stimulated tonicity of the parasympathetic nervous system. Compared to the
      controls, the test patients developed higher exercise tolerance and lower
      reactivity of the central hemodynamics in all the exercise tests.

PMID- 10900864
TI  - [Melatonin production in hypertensive patients].
AB  - Hypertensive subjects were examined for production of melatonin. In severe
      hypertension night levels of melatonin diminished, the day production is as in
      the controls. The role of melatonin in pathogenesis of essential hypertension is
      discussed.

PMID- 10900865
TI  - [Actovegin treatment of duodenal ulcer associated with ischemic heart disease and
      diabetes mellitus].
AB  - Actovegin, a deproteinized hemoderivative, was used to correct bioenergetic
      defects of duodenal mucosa, to reduce inflammatory-cell infiltration, to
      stimulate blood supply of patients with duodenal ulcer associated with ischemic
      heart disease or diabetes mellitus. As shown by the results obtained in 194
      patients (119 males and 75 females), adjuvant actovegin in patients with duodenal
      ulcer associated with ischemic heart disease and diabetes mellitus stimulates the
      ulcer healing, prolongs the recurrence-free interval. It can be used both in
      outpatient departments and specialized hospitals.

PMID- 10900866
TI  - [Vegetative functions characteristics in patients with chronic gastritis].
AB  - Basing on examination of 311 patients with chronic gastritis (CG), three
      clinicopathogenetic variants of the disease course were determined. Variant 1 is
      characterized by superficial involvement of the gastric mucosa, normal or
      hyperactive secretory function, normokinetic motor type, dominating
      parasympathetic vegetative tonicity and reactions of the parasympathetic type,
      rare segmental disorders, absolute hyperhistaminemia. Variant 2 is characterized
      by moderate atrophy of the gastric glands, secretory and motor hypofunction,
      unaffected vegetative status, normohistaminemia. Variant 3 runs with severe total
      atrophy of the gastric glands with secretory insufficiency and gastric
      hypokinesia, primarily sympathetic suprasegmental vegetative disorders, marked
      segmental disorders, absolute hypohistaminemia.

PMID- 10900867
TI  - [Melatonin and serotonin in inflammatory colon diseases and colorectal
      neoplasms].
AB  - Patients with inflammatory intestinal diseases and colorectal adenocarcinoma in
      sigmoid mucosa were examined using light and electron microscopy,
      immunohistochemical tests, radioimmunoassay and morphometry. Functional
      morphology of the general population of the endocrine cells and apudocytes
      producing melatonin and serotonin as well as urine excretion of 6
      sulfatoxymelatonin changed in quality and quantity. The parameters showed
      specificity depending on clinicomorphological variant of colorectal pathology.
      The findings provide additional criteria in diagnosis and prediction of the
      course of different types of inflammatory and tumor affections of the colon.

PMID- 10900868
TI  - [Role of red blood cell changes in chronic occlusion of low limb arteries].
AB  - To study morphofunctional status of red blood cells, peripheral blood was
      investigated in 49 patients with chronic occlusions of low limb arteries (COLLA)
      and 23 healthy donors matched by gender and age. Circulation in the limbs was
      assessed by infrared thermography. Photometry provided data on microrheological
      properties of blood by reversible red cell aggregation. Scanning electron
      microscopy examined superficial red cell architectonics. The findings evidence
      that red cell aggregation in COLLA patients enhances irrespective of the ischemia
      degree while dysaggregation declines, polymorphism of red cell polymorphism grows
      with an increase of the number of transformed cells varying by degeneration
      stage. The above changes in red cell microrheology contribute to impairment of
      microcirculatory perfusion and tissue hypoxia in COLLA patients.

PMID- 10900869
TI  - [Motor and secretion function of stomach and duodenum, duodenogastric reflux in
      patients with duodenal ulcer].
AB  - Gastric secretion, motor function and tonicity of the stomach and duodenum,
      duodenogastric reflux were studied in inpatients with two clinicopathogenetic
      types of duodenal ulcer: observed at young age (type 1) and in later life (type
      2). The examination included pH-metry with simultaneous balloon cimography,
      chromogastroduodenoscopy with Kongo-red, tests for Helicobacter pylori conducted
      on the biopsy samples. All the patients were found to have continuous acid
      production. High acid production was more frequently registered in males with the
      disease type 1, the lowest production was in females with the disease type 2.
      Duration of the acid inflow into the duodenum in patients with the disease type 2
      was greater than that in young subjects. Mild ulcer was associated with moderate
      acidity in the duodenum, in severe ulcer the acidity was very high. Males with
      the disease 1 and 2 and females with type 2 had hyperkinetic, hypertonic gastric
      motor function. In duodenal ulcer prevalent is hypertonic, hyperkinetic type of
      duodenal motor function being most frequent among males with the disease type 2.
      Duodenogastric reflux occurs more often in patients with intensive acid
      production associated with hypotonic, hypokinetic motor type and duodenal tone.

PMID- 10900870
TI  - [Emotional disturbances in patients with infectious mononucleosis and serous
      meningitis].
AB  - 30 patients with infectious mononucleosis (19 females and 11 males) and 30 ones
      with serous meningitis (16 females and 14 males) aged 16-35 years admitted to
      hospital on the disease day 2-14 were examined clinicopsychologically,
      clinicofunctionally and using laboratory tests. The examination has revealed
      emotional disturbances in 40% of patients with serous meningitis and 20% of those
      with infectious mononucleosis. Clinical manifestations were characterized by
      polymorphism, combination of somatovegetative and anxiodepressive disorders.
      Personality accentuations in the patients are described.

PMID- 10900871
TI  - [Differential approach to administration of cosaar].
AB  - Effects of cosaar (MSD) on central hemodynamics and microcirculation were studied
      in 20 patients with arterial hypertension under acute pharmacological test and on
      the treatment week 2, 6 and 8. Two variants of hemodynamic response were
      registered: hypokinetic and hyperkinetic. Unidirectional hemodynamic changes
      occurred both in short- and long-term therapy. This allows to use the short
      course for differential choice of patients for cosaar therapy. The best effect of
      cosaar is expected in patients with a hyperkinetic variant of the hemodynamic
      response under the short treatment course.

PMID- 10900872
TI  - [Vasoactive effects of femostone in women with metabolic postmenopausal
      syndrome].
AB  - The metabolic postmenopausal syndrome (MPS) is characterized by a complex of
      metabolic disorders: lipid (76%), purin (56%), calcium-phosphorus (61%). There is
      also a rise in amplitude of spontaneous platelet aggregation (61%) and fibrinogen
      levels (78%). Clinically, these phenomena manifest in arterial hypertension and
      defective cerebral circulation. An estrogen-histogen drug femoston was tried for
      clinical effectiveness and tolerance in 40 females with MPS. Femoston was used in
      long-term regimen for 12 months. The response was observed in all the patients,
      all the above parameters underwent positive changes. The drug was well tolerated,
      side effects were moderate. No withdrawals occurred.

PMID- 10900873
TI  - [Quamatel application in three-drug eradication therapy of duodenal ulcer and
      gastroduodenal ulcerations associated with helicobacter pylori infection].
AB  - Combination of famotidine, amoxicilline and metronidasole was applied in the
      treatment of 71 patients with erosive-ulcerative affection of the upper
      gastrointestinal tract. The combination more rapidly relieved pain (within 5-6
      days), dyspepsia (for 7-8 days), enabled healing of the ulcer defect for 2-3
      weeks, raised gastric pH to 5.7-5.8 and eradicated Helicobacter pylori in 87.3%
      of the cases.

PMID- 10900874
TI  - [Lochein - a novel hepatoprotective drug].
AB  - A trial of a novel hepatoprotective plant drug lochein (Salsola extract)
      developed in Russia was performed in 110 patients with a verified chronic
      hepatitis of viral (73 patients) or alcohol (36 patients) etiology versus well
      known hepatoprotector corsil given to 40 patients. Lochein demonstrated more
      potent effect than corsil.

PMID- 10900875
TI  - [Current knowledges of Banti's syndrome].

PMID- 10900876
TI  - [Severe course of obstructive sleep apnea in female with hypothalamic syndrome
      and hypophyseal adenoma].

PMID- 10900877
TI  - [New treatment of pain and fever in rheumatoid arthritis and arthrosis. The first
      cyclooxygenase-2 inhibitors show promising results].

PMID- 10900878
TI  - [Article series on glia cells. Thousands of billions of dynamic individuals].

PMID- 10900879
TI  - [Astrocytes--anonymous cells in the brain, participating in neurasthenic
      symptoms].
AB  - During rehabilitation after brain damage due to stroke or trauma, or after
      meningitis, patients often suffer from mental fatigue and decreased capacity for
      concentration and learning. We hypothesize that one pathogenic cause of these
      symptoms could be a failure on the part of astroglia to remove glutamate and K+
      from synaptic regions during glutamatergic transmission. As astroglial support of
      neuronal glutamate transmission has been shown to be of utmost importance, such
      an astroglial failing might lead to a decreased signal-to-noise ratio in
      glutamatergic neurotransmission, especially when the transmission is intense for
      a considerable time period. Three aspects of astroglial failing are focused upon:
      decreased capacity of the astroglial glutamate transporters, depolarization of
      the astroglial network, and uncoupling of the gap junction coupled astroglial
      network. It has been shown that several neuroactive substances, present within
      the nervous system even long after damage or infection, influence upon these
      three astroglial properties.

PMID- 10900881
TI  - [Rheumatic diseases in children as an important specialty. Bone marrow
      transplantation is the hope for the most severely ill patients].
AB  - Chronic inflammatory joint disorders can be viewed as a spectrum of disease
      presenting one set of characteristics during childhood and another in adulthood.
      Few of the disorders are specific for children of a specific age, even if some
      conditions might be very rare in certain age groups. Juvenile idiopathic
      arthritis is a new name suggested for pediatric chronic inflammatory joint
      disorders. Drug therapy is based on the same principles as for adults: an
      aggressive approach with NSAID-drugs and low dose methotrexate in combination
      with local steroid injections. New drugs like TNF-blockade and COX-2 inhibitors
      are almost untested in children, with the exception of etanercept which has been
      studied in children with polyarticular disease and proven to be very effective.
      For rare cases with very severe joint disease hematopoietic stem cell
      transplantation is under evaluation.

PMID- 10900880
TI  - [The up and down world: glia makes nerve cells!].

PMID- 10900882
TI  - [Inventory of geriatric psychiatry in Sweden. In short supply where demand does
      not determine resource allocation].
AB  - In 1999 The Swedish Society for Old Age Psychiatry conducted an investigation in
      all Swedish counties in order to survey existing organizations and resources for
      medical services intended for elderly people with psychiatric complaints. In some
      counties there were no out-patient units specifically aimed at elderly people
      with psychiatric diseases, while more than half had no out-patient units for the
      large group of elderly with psychiatric ailments other than dementia. The total
      number of beds was far less than international recommendations. Less than 5 per
      cent of the total number of Swedish psychiatrists and geriatricians hold
      positions exclusively for geriatric psychiatry. Access to geriatric psychiatry
      resources appears to be unevenly distributed, and may be found mainly in or near
      university cities.

PMID- 10900883
TI  - [Hospice de Beaune--a palace for the sick].

PMID- 10900884
TI  - [A comment to the article by Torbjorn Tannsjo on "severe mental retardation": A
      necessary even when not sufficient contribution to the debate].

PMID- 10900885
TI  - [Legislation concerning mentally disabled criminal offenders: the question of
      responsibility must be separated from the question of penalty].

PMID- 10900886
TI  - [Torbjorn Tannsjo answers the criticism: progress to send a mentally disabled to
      prison].

PMID- 10900887
TI  - [The National Board of Health and Welfare's new guidellines on drug handling. Let
      the delegation of drug handling be the responsibility of the acting heads].

PMID- 10900888
TI  - [The National Board of Health and Welfare answers: It's still possible to
      delegate drug handling in home care to nurses' aides].

PMID- 10900889
TI  - [Reflections of practical problems with drug information or Where can I put the
      rubbish?].

PMID- 10900890
TI  - [Private practitioners and the 65-year age limit: no savings gained when well
      functioning practices are counteracted].

PMID- 10900891
TI  - [Evidence-based medicine. A real tool for the shop-floor of health care service].

PMID- 10900893
TI  - [Effect of antibiotics on symptoms and complications of sore throat. Comments on
      a meta-analysis from the Cochrane Collaboration].

PMID- 10900892
TI  - [The systematic review is the foundation of evidence based medicine. One of the
      most important contributions to clinical medicine of the past decade].
AB  - The traditional narrative review has been shown repeatedly to be biased, mostly
      towards exaggerated treatment size effects. In contrast, the systematic review
      follows a strict protocol regarding focused questions, explicit criteria for
      literature searches, inclusion and exclusion criteria, critical appraisal and a
      synthesis which is quantitative when appropriate. There is empirical evidence
      that bias is reduced and that the conclusions reached have greater validity for
      the construction of treatment guidelines. In this paper three sources of
      systematic reviews are identified: the Cochrane Library, reviews published in
      peer-reviewed journals, and assessments of health technology (HTA-reports).
      Editors are encouraged to publish systematic reviews after proper critical
      appraisal, and readers are advised to search for such reviews when in need of
      guidance on important clinical questions.

PMID- 10900894
TI  - [Structured care program yielded good results in severe anorexia nervosa].
AB  - Between 1994 and 1998, 19 patients averaging 21 years of age (range 17-24) with
      severe anorexia nervosa were treated according to a special protocol including
      enteral nutrition by the nasogastric route, firmly implemented supervisory
      strategies and simultaneous psychiatric support. Mean body mass index increased
      from 13.8 (10.4-16.3) at admission to 15.2 (13.0-18.2) at discharge after an
      average hospital stay of 24 days. No serious complications occurred. At a follow
      up in 1999, a questionnaire concerning the protocol was answered by 13 of the
      patients. Most of them experienced the hospital stay as trying, but
      retrospectively perceived the tube feeding and supervisory strategies as
      necessary.

PMID- 10900895
TI  - [5-year experience from an anorexia and bulimia clinic. Half of the younger
      patients recovered after nine months].
AB  - We present patient data including diagnosis, follow-up and number of sessions.
      Data for patients 18-25 years of age with anorexia nervosa are also presented.
      Treatment methods for the various eating disorders are presented. Two projects
      are presented, one for patients 13-18 years of age and another one for bulimic
      patients over 18 years. Half of patients 13-18 years of age did not fulfill
      criteria for an eating disorder at follow-up nine months after the initial
      session.

PMID- 10900896
TI  - [The effect of estradiol on human endometrial cancer. Experimental in vivo and in
      vitro studies].
AB  - In this article our findings concerning estradiol-induced changes in steroid
      receptor activation, cell kinetics and tumor growth regulation during in vivo and
      in vitro progression of human endometrial adenocarcinomas are reviewed. We found
      major changes such as alterations in estrogen receptor function and post-receptor
      alterations in tumor growth regulation. Our results suggest that although the
      development of these alterations is genetically determined, they may to some
      extent be modified by circulating estradiol levels. No biological changes were
      found, suggesting that the use of menopausal estrogen replacement therapy by
      women with non-diagnosed endometrial cancer may increase their death rate.

PMID- 10900897
TI  - [Screening for hemoglobinopathies at a knowledge center in Copenhagen. Resources
      should be allocated to solve a growing health problem in the Nordic countries].
AB  - Increased immigration to the nordic countries of people from areas in which
      hemoglobinopathies are common diseases has resulted in an increased frequency of
      individuals heterozygous for serious hemoglobin disorders such as beta
      thalassemia and sickle cell disease. Thus, in Copenhagen County, about 4 per cent
      of the immigrants from these countries are carriers of one of these diseases. A
      center for hemoglobinopathies has been established in Copenhagen County, dealing
      with diagnostics, screening procedures, genetic counseling, prenatal diagnosis,
      education and treatment of various hemoglobin disorders. In collaboration with
      Rigshospitalet and the laboratory serving general practitioners, a screening
      program for pregnant women of relevant ethnic origin has been established,
      capable of servicing the entire Copenhagen area.

PMID- 10900898
TI  - [The rumour about the death of debriefing is significantly exaggerated!].

PMID- 10900899
TI  - [Psychological debriefing--time to abolish the model or...?].

PMID- 10900900
TI  - [ASA or clopidogrel?].

PMID- 10900901
TI  - [Evidence-based use of the PET in cancer diagnosis?].

PMID- 10900902
TI  - [Non-substantial advertising of PET].

PMID- 10900903
TI  - [Welcomed introduction of evidence-based medicine].

PMID- 10900904
TI  - [Can laboratories rely on diagnostics-companies?].

PMID- 10900905
TI  - [Vitamin B12 and our aluminum requirements].

PMID- 10900906
TI  - [PS on homocysteine as a risk factor of cardiovascular disease].

PMID- 10900907
TI  - [The malaria situation in the WHO European region].
AB  - The number of indigenous malaria cases in European region peaked in 1997, when
      77,985 cases were officially reported. These were caused almost exclusively by P.
      vivax, P. falciparum being restricted to a rather limited number of cases in
      Tajikistan only. Another important problem in the European Region is the
      importation of malaria associated with a high fatality rate from tropical endemic
      countries. There were 841 cases of malaria in Armenia, 567 of which were locally
      transmitted, 30 out of 81 districts recorded malaria cases. 89% of the indigenous
      cases were registered in Masis district, in the Ararat valley. In 1998, total
      number of cases increased to 1156. Of the 542 indigenous cases registered, 376
      were in Masis district. 9911 cases were officially reported in 1997 in Azerbaijan
      and 5175 cases in 1998. Approximately half of malaria cases were reported from
      seven districts: Nakhichivan (10.4%), Imishli (14.6%), Fizuli (8.1%), Sabirabad
      (6.8%), Saatly (6%), Bejlagan (5.6%) and Bilasuvar (4.8%). Local transmission is
      also reported from the periurban areas of Baku, where many displaced people are
      living in temporary shelters. In 1997, a total of 30,054 malaria cases were
      officially registered in Tajikistan, of which 85.3% occurred in the Khatlon
      region, 10.5% in Dushanbe region, 3.5% in Gorno-Badakhshan region and 0.7% in
      Leninabad region. Following implementation of malaria control activities with WHO
      assistance, the number of malaria cases officially registered in 1998 dropped to
      19,361 (187 were cases of falciparum malaria). A dramatic change occurred in
      malaria situation in Turkmenistan in 1998, when 115 indigenous cases were
      registered. The majority of malaria cases (104) were registered in the Kushka
      district, in south-east of Turkmenistan, among military service personnel. In
      recent years, the Government of Turkey has renewed its efforts to fight malaria,
      incorporating them into GAP with support from UNDP and WHO. In 1998, 36,451 cases
      were reported, 87.1% from southeastern Anatolia, 8.7% from Adana area and 4.2%
      from other areas of Turkey. The epidemics in Armenia, Azerbaijan, Tajikistan and
      Turkey are having a considerable impact on the malaria situation in neighbouring
      countries of the European Region. Malaria cases have been imported from Turkey
      mainly to western Europe; from Azerbaijan to the Russian Federation, Georgia, and
      the Republic of Moldova; and from Tajikistan to the central Asian republics and
      to the Russian Federation. WHO made all possible efforts to mobilize and
      coordinate assistance from international community. WHO/EURO organized missions
      to those NIS where there is a risk of malaria epidemics. Most of the very limited
      funds reserved for epidemic prevention and control were immediatelly used to
      provide a limited stock of antimalarial drugs and to help the national
      institutions in Kazakhstan and Uzbekistan implement antimalarial activities. In
      1997, with the financial support of the Italian Government and the technical
      assistance of the Instituto Superiore di Sanita in Rome (WHO collaborating centre
      for research and training in planning tropical disease control) and of the
      Martsinovsky Institute of Medical Parasitology and Tropical Medicine in Moscow
      (WHO collaborating centre on vivax malaria), the training of health personnel in
      the field of malaria diagnosis, treatment and control was initiated in Armenia,
      Azerbaijan, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. In
      1996-1997, Japan provided financial support for a large malaria control project
      in Tajikistan, and Norway supported activities carried out in 1997 to tackle the
      malaria outbreak in Armenia. In 1997-1998, Italy supported malaria prevention
      activities in Kazakhstan, Kyrgyzstan and Uzbekistan, and some of the malaria
      activities carried out in Tajikistan under the integrated Management of Childhood
      Illness initiative. Several training courses and seminars were carried out in
      Turkey in 1998 by the national malaria contro

PMID- 10900908
TI  - [The goals and tasks of the Roll Back Malaria WHO Cabinet Project].
AB  - WHO's Roll Back Malaria Cabinet Project (RBM) has been initiated by WHO Director
      General Dr. G. Brundtland in 1998. The World Health Organization, The United
      Nation's Children's Fund, the United Nation's Development Programme and World
      Bank have joined forces to fight malaria, which kills more than one million
      people a year. RBM is being launched at time of growing and investment in
      malaria, which still remains grossly underfunded. RBM is different from previous
      efforts to fight malaria. The project is working not only through new tools for
      controlling the disease but also by involving and strengthening the health
      services to affected population. This pattern of activities is close to Russian
      version of malaria eradication programme that had been carried out with the
      success in the former Soviet Union in the 1950s. RBM seeks to reduce
      substantially the human suffering and economic losses due one of the most costly
      diseases. Malaria causes an estimated 300 to 500 million acute cases per year.
      Malaria is a disease of young and the poor, many of them children who live with
      no easy access to health service. RBM goal is a significant reduction--ideally
      halving within ten years--in the global burden of disease associated with
      malaria. RBM purpose is to create an environment that helps countries develop
      policies and implement relevant elements of RBM strategy. There are six elements
      to roll back malaria. They are: early detection of malaria illness; rapid
      treatment of those who are ill; multiple means for preventing infection;
      strengthening of health sector and intersectoral activities; a powerful sustained
      social involvement and movement; focused research for new tools and better
      implementation. New tools are available to combat malaria. They include among
      others: rapid diagnostics; new drugs (artesunates) and new means for delivery;
      impregnated bednets; new means for predicting epidemics (satellite mapping). WHO
      will be coordinating the RBM project. Endemic countries and affected populations
      have identified malaria as a priority health issue. Activities will cut across
      WHO programmes and regions to support government, to improve technical efficiency
      and capacity, to optimize resource allocation, utilization and mobilization.

PMID- 10900910
TI  - [Malaria in Azerbaijan].
AB  - Rapid deterioration of the malaria situation set in after 1990, when 22 cases
      were reported. The number increased to 667 in 1994, 2840 in 1995 and reached
      13,135 in 1996. The main reason for the deterioration was a sharp worsening of
      socioeconomic conditions and the displacement of nearly one million people from
      war-stricken zones. With international assistance from WHO, ENI (Italy), MSF
      (Belgium), the Ministry of Health resumed limited malaria control activities: in
      1997, 9911 cases were officially reported and 5175 cases in 1998. Approximately
      half of malaria cases were reported from seven districts: Nachishivan (10.4%),
      Imishli (14.6%), Fizuli (8.1%), Sabirabad (6.8%), Saatly (6%), Bejlagan (5.6%)
      and Bilasuvar (4.8%). 1737 malaria cases were detected during 7 months of 1999,
      4007 cases were reported during 7 months of 1998.

PMID- 10900909
TI  - [The malaria situation in the WHO eastern Mediterranean region].
AB  - About 45% of the population of the Eastern Mediterranean Region live under the
      risk of both falciparum and vivax malaria, and additional 15% under the risk of
      P. vivax alone. The estimated annual number of malaria cases is about 14 million,
      out of which 95% occur in four countries: Afghanistan, Somalia, Sudan and Yemen.
      In Afghanistan malaria is endemic throughout the country at altitude below 1500
      m. About 80-90% of malaria cases belong to P. vivax, the rest to P. falciparum
      (the latter is prevalent mostly in the South and in Badakhshan). In Islamic
      Republic of Iran 16% of the population live in initially non-malarious areas, 66%
      in areas freed from malaria, 12% in areas with sporadic transmission, mostly of
      P. vivax, and only 6% in areas of continuous transmission with a high proportion
      of P. falciparum. As much as 77% of the recorded cases belong to the latter
      territories. Iraq. After the Gulf war, the situation deteriorated in the three
      north-eastern governorates, and malaria spread outside this area and rooted in
      the south (Basra). Syria. Transmission of P. vivax still occurs, mostly along the
      western part of the border with Turkey and in the north-eastern corner of the
      country. At present, there are three areas that causes concern along borders
      between the European and Eastern Mediterranean Regions: Afghanistan is a source
      of importation of malaria to all its neighbours; areas on the borders between
      Iran, Azerbaijan and, to some extent, Armenia; 4 northern governorates of Iraq
      and parts of southeastern Turkey, with repercussions in Syria and, to a Lesser
      extent in Iran, along its western border. To some extent, Cyprus is also
      threatened, since importation of malaria to the northern part of the island from
      Turkey has been documented. In practical terms, there is a need for co-ordination
      of antivectorial activities and standardization of control methods between the
      countries with strong programmes and relatively intense transmission in border
      areas, i.e. between Iran, and Azerbaijan, Iraq and Turkey, Syria and Turkey.

PMID- 10900911
TI  - [The malaria situation in Afghanistan].
AB  - Malaria is endemic throughout the country at altitude below 1500 m. About 80-90%
      of malaria cases belongs to P. vivax, the rest to P. falciparum. Malaria has gone
      out of control in Afghanistan in the past 20 years. The annual number of cases is
      estimated at 2-3 million, the number of officially reported was 288,070 in 1998.
      Out of the 20.5 million population of Afghanistan (1998 estimates), more than 12
      million are to be living in malaria endemic areas. A field study to evaluate the
      susceptibility of P. vivax and P. falciparum to chloroquine was conducted in four
      sites of the eastern region. The study revealed 100% susceptibility of P. vivax
      while P. falciparum indicated an alarming degree of resistance.

PMID- 10900912
TI  - [Malaria in Georgia].
AB  - There were 17 indigenous P. vivax malaria cases registered in Georgia in 1996
      1998. In 1996, 3 cases were reported and 14 cases in 1998. There were 23
      indigenous P. vivax malaria cases detected nine months of 1999.

PMID- 10900913
TI  - [The malaria situation in the Islamic Republic of Iran].
AB  - In 1998 there were 32,616 cases of malaria registered in the Islamic Republic of
      Iran, 20.34% of which were falciparum malaria.

PMID- 10900914
TI  - [The malaria situation in the Russian Federation (1997-1999)].
AB  - Profound socio-economic changes within the CIS countries in the 1990s brought a
      lot of negative changes in malaria prevention in targeted countries. The
      previously stable connection and cooperation in prophylactic activities have been
      interrupted. Supply of antimalarials, insecticides and equipment had been
      stopped. Many qualified cadres in the sanitary-epidemiological services in the
      countries were lost. Because of difficult economic situation they had to change
      their occupation and place of job. After prolonged period of a stable benign
      epidemiological situation within Russia the number of imported cases started to
      grow up. The sharp increase of imported malaria cases from Azerbaijan and
      Tajikistan had been noticed since 1994 (Tab. 1). For the first time in the
      history of malaria registration the number of cases imported from the CIS
      countries has been exceeded the number of malaria cases imported from all other
      countries in the world in 1995. Later in the end of the 1990s the imported
      malaria cases has been registered in Russia from some other CIS countries apart
      from Azerbaijan and Tajikistan. There were malaria cases imported from Armenia
      (13 cases), Moldavia (2), Turkmenistan (2), and Uzbekistan (2) in 1998. The
      number of imported malaria cases in Russia in 1999 (Jan-July) is 437. There is no
      information about introduced or indigenous malaria cases registered until now]
      within Russia. There were 13 introduced malaria cases as the result of numerous
      imported ones. 13 introduced cases have been registered in 10 oblasts
      (administrative regions of Russia). This number has been increased to 53 (!) in
      1998 in 20 oblasts. There was one local outbreak of P. vivax malaria in Izberbash
      settlement (Dagestan). Number of indigenous malaria cases were 5 (1996), 18
      (1997), 1 (1998). The contra-epidemic measures in Izberbash have included active
      cases detection and treatment indoor insecticide spaying and one tour of mass
      primaguine treatment during interseasonal period of time. Additional indigenous
      cases after imported and introduced ones have been detected in Krasnodar (1
      cases), Samara (1), Tolyaty (1), and Cherkessk (5) in 1998. One induced P.
      falciparum malaria case has been detected Moscow in 1998. Medical nurse from
      urological branch of the Moscow hospital No. 29 has penetrated by syringe needle
      her hand after performing of intravenous injection to the patient with imported
      P. falciparum malaria. No other induced cases have been detected. Because of
      local administrative problems with primaquine supply not all P. vivax malaria
      cases have received complete treatment. As the result of these events there was
      malaria relapsed cases registered every year. The actual number was 20 (1993), 37
      (1994), 45 (1995), 59 (1996), 99 (1997). Due to late appearance of patient with
      P. falciparum malaria before medical staff and as a result late diagnosis and
      late and some time inappropriate treatment there were several lethal malaria
      cases registered [table: see text] every year. Inappropriate treatment means that
      treatment of P. falciparum malaria cases was consisted of chloroquine only. The
      cumulative number of lethal cases in 1994-1997 was 12, and the same number in
      1998 was 6. One should mention that one lethal case in 1998 in Volgograd was due
      to P. vivax. The subject was chronic alcoholic and combination with P. vivax
      malaria brings him to death. Some calculation reveals the risk of resurgence of
      malaria in Russia. If one analyses all P. vivax imported cases from the point of
      view of time and place of detection the following picture would be emerged: 83%
      of all imported cases has been localized within cities, and 17% only--in rural
      areas. Half of the latter has been appeared during cold part of years when
      transmission was impossible. The result of approximately 200 imported cases has
      been appeared in a right time and place there were 75 introduced cases.

PMID- 10900915
TI  - [The malaria situation in the Syrian Arab Republic].
AB  - The problem of malaria in Syria is not large one, and because of good
      surveillance and management, malaria cases have decreased from 626 cases in 1995
      to 68 cases in 1998, of which 14 cases were indigenous ones. Vivax malaria cases
      are registered in the country only.

PMID- 10900916
TI  - [The malaria situation in Turkey].
AB  - Turkey is the last country in the temperate zone on the edge of the European
      continent in which malaria is prevalent at endemic and occasionally epidemic
      proportions. Malaria was the most significant vector borne disease constituting a
      serious healthy problem until it was suppressed in 1965. Following the
      establishment of malaria eradication program in 1957 which began operation in
      1960 after many years of malaria control, the incidence of malaria decreased
      annually and the stricken areas became more and more restricted. Unfortunately,
      an agricultural development program initiated in mid 70's in the Cukurova Plain
      caused a substantial migration of workers from the eastern areas where malaria at
      that time was more prevalent. This population movement together with the
      industrial expansion that took place resulted in a serious epidemic of vivax
      malaria in 1977 in the provinces of Adana, Icel and Hatay, where 101,867 cases
      were reported. The following years, Turkey targeted to reduce the number of
      malaria cases to less than 800 by 1984. After 1985, the number of malaria cases
      in the country has continued to increase and in the past five and six years a
      serious malaria epidemics has been building up in the southeastern provinces. The
      gravitational center of the disease has now moved from the Cukurova to the GAP
      area in South East Anatolia and beyond. The indicator of this movement is that
      89% of total cases in 1998 is concerning to the GAP region. By the year 1998 the
      number of reported cases were 36,842. The common parasite type is P. vivax in the
      country. The other types are generally imported from other countries. These are
      Syria, S. Arabia, Pakistan, Afghanistan, Yemen, Nigeria, India, Malaysia, Ghana,
      Indonesia, Sudan etc. Malaria cases are registered in bordering areas of the
      country constantly. The suggested solutions for Malaria control in bordering
      areas are: 1. To establish control laboratories in customs in order to take blood
      from persons who come from risky areas for malaria. When positive cases are found
      these laboratories will also provide free treatment. 2. East country should give
      information about the malaria situation in their country to the other countries.

PMID- 10900917
TI  - [Malaria in the Republic of Tajikistan].
AB  - There were 200-300 malaria cases registered annually in the republic up to 1992.
      Due to civil war, interruption of antimalarial control measures and mass
      returning of refugees from Afghanistan epidemiological situation deteriorated
      since 1994. In 1997, 29,794 malaria cases were officially registered. Estimated
      number of cases were 200,000-500,000. There were local transmission of falciparum
      malaria. Since 1998, Tadjikistan receives financial support from Japan, Italy,
      Norway, and technical support from WHO. National Programme of malaria control has
      been designed and adopted by the Government in 1997. Laboratory diagnostics of
      malaria was implemented. Network of special antimalarial centres were established
      on central, regional and district levels. Mass treatment of population with
      primaquine and indoor residual spaying with piretroid have been performed in 1998
      and 1999. In 1998, there were 19,351 malaria cases of which 10,268 were
      microscopically confirmed. During 6 months of 1999 2531 malaria cases were
      registered, 2246 among them were microscopically confirmed.

PMID- 10900918
TI  - [The epidemic situation with malaria in Turkmenistan].
AB  - As a result of comprehensive research on the causative agents and vectors of
      malaria and wide use of synthetic antimalarials and highly effective residual
      insecticides, endemic malaria was eliminated in Turkmenistan by 1960. During the
      period 1965-1980, 23 local cases of malaria were recorded in Turkmenistan. These
      local cases were confined to the regions of Mary and Akhal, on the borders of
      neighbouring countries. In 1998 the epidemiological situation in the country
      worsened and local transmission of infection resumed. During the year the number
      of cases recorded was 137:134 being a first diagnosis of the disease and three
      being relapsed cases. In comparison with 1997, the previous year, incidence was
      up by 123 cases (a 9.7-fold increase), while the incidence of imported cases of
      malaria went up by 11 (a 2.2-fold increase), principally in Dashkhovuz and Lebar
      regions, being brought in from malaria foci in Gushgin district, Turkey,
      Azerbaijan and Tadjikistan. Local transmission of malaria went up by 111 cases (a
      27.7 fold increase); 108 cases were recorded in Gushgin district, Mary region.
      The first case of malaria in Gushkin district was detected in June 1998. At that
      time there were five active foci. The approximate number of inhabitants in the
      active focus area was 10,000. The appearance of local malaria in border districts
      was caused by the periodic influx of infected mosquitos from neighbouring
      countries (Afghanistan).

PMID- 10900919
TI  - [The epidemic situation with malaria in Uzbekistan].
AB  - In the past five years (1994-1998), 223 cases of imported malaria were recorded
      in the Republic (Table 1), 190 of which were from countries in the Commonwealth
      of Independent States (CIS) and 33 from other countries. It is noteworthy that
      the number of cases imported from Tadjikistan--a country that borders eight of
      the Republic's 12 regions (oblasts)--has increased each year (12 in 1994, 69 in
      1998). Some 25% of the population of our Republic live in the 67 cities and
      regions bordering Tadjikistan, Turkmenistan, Kazakhstan, Kyrgyzstan and
      Afghanistan. 35.5% of the cases of imported malaria have been registered in
      Surkhandarin region, which borders Afghanistan and Tadjikistan. Seventy-four
      (imported) cases of malaria were registered in the Republic in 1998, of which 17
      (23%) were children under 14 years of age. Cases were registered in eight regions
      of the Republic and in the city of Tashkent. Thirty-six patients were detected in
      Surkhandarin region. Malaria was imported mainly from Tajikistan (69 cases) and
      Azerbaijan (two cases), as well as from Afghanistan (two cases) and India (one
      case). The infectious agent of vivax malaria was identified in 94.6% of cases,
      while in four cases it was found to be that of falciparum malaria. Three cases of
      falciparum malaria were registered for the first time in Surkhandarin region
      (imported from Tadjikistan) and one in the city of Tashkent (imported from
      Afghanistan). A large proportion of malaria cases (53, or 71.6%) were detected in
      the period from June to September, which is the time of high risk of infection.
      In the first six months of 1999, 15 cases of imported tertian malaria were
      recorded in the country as a whole, with six in Tashkent and Surkhandarin region,
      two in Fergana region and one in Samarkand region. Importation occurred mainly
      from Tajikistan (12 cases), with Azerbaijan, Kazakhstan and Afghanistan each
      accounting for one case. In order to prevent the spread of the infection from
      neighbouring malarious countries, steps are being taken to make medical personnel
      more alert to this threat, with the aims of ensuring prompt detection of people
      suspected of having malaria, improving the quality of laboratory diagnosis and
      treatment, and strengthening vector control.

PMID- 10900921
TI  - [A case report of tropical malaria in the city of Kaliningrad].

PMID- 10900920
TI  - [Local cases of tropical and tertian malaria in Moscow Province].

PMID- 10900922
TI  - [Rapid methods for the diagnosis of tropical malaria].

PMID- 10900924
TI  - [The coloring of the head capsule of Anopheles (Diptera, Culicidae) larvae and
      the use of this trait for species diagnosis].
AB  - The paper describes the colour of the stage IV larval head capsule in Anopheles
      pulcherrimus and An. superpictus and discusses whether this the use of this sign
      can be used to classify malaria mosquitoes.

PMID- 10900923
TI  - [The malarial mosquitoes of Russia (the genus Anopheles)].

PMID- 10900925
TI  - [The modulation of Plasmodium falciparum virulence as a factor in the self
      regulation of the malarial parasitic system].
AB  - Higher Plasmodium falciparum virulence is one of the major factors that
      contributes to the development of severe malaria and leads to death. However, the
      nature of virulence and its time course are not so far fully understood. The
      authors have made a published data-based hypothesis that the virulence of P.
      falciparum strains circulating in the malaria endemic areas of tropical Africa is
      not strictly genetically determined. The virulence of P. falciparum increases
      with its passage through the non-immune organisms of the infected persons. This
      mechanism of virulence modulation ensures the survival of the parasite in the
      human population with a considerable communal immunity. To test the validity of
      the hypothesis, the authors have used a mathematical analytical method to assess
      the published data on malaria mortality in some areas of tropical Africa. The
      results of the analysis have shown close values of actual and expected data.

PMID- 10900927
TI  - Transformational outcomes associated with parenting children who have
      disabilities.
AB  - In this study we explored transformations--significant and positive changes--in
      the lives of parents of children with disabilities. In the first phase of the
      study, we interviewed 15 parents of children with disabilities about their
      experiences as parents. Results were qualitatively analyzed to develop themes. In
      the second phase, we surveyed 80 parents using an instrument that measured
      agreement with the themes from the first phase. Results indicated that most
      parents reported many positive changes in their lives as a result of parenting a
      child with a disability. These included three major areas: (a) personal growth,
      (b) improved relations with others, and (c) changes in philosophical or spiritual
      values.

PMID- 10900926
TI  - [The immunological aspects of tropical malaria related to the development of an
      antimalarial vaccine].

PMID- 10900928
TI  - Phenotypic checklist to screen for fragile X syndrome in people with mental
      retardation.
AB  - The development of a phenotypic checklist for identifying people with fragile X
      syndrome is described. The checklist was designed to identify people with
      developmental disabilities of unknown causes for molecular genetic testing for
      fragile X syndrome. The list consists of 28 items (7 on physical characteristics
      and 21 on behavioral features). Validation data were collected for 110 boys and
      men with fragile X syndrome and for 79 members of a control group, matched for
      CA, level of cognitive development, and social (mal)adaptation. On the basis of
      checklist results, those boys who are likely to be diagnosed as having fragile X
      syndrome can be identified. The screening list can be considered to be a
      consistent, reliable, and valid instrument.

PMID- 10900929
TI  - "I can speak for myself": involving individuals with intellectual disabilities as
      research participants.
AB  - The Lifespan and Disability Project, a 2-year qualitative study, was designed to
      enhance understanding of social integration by including the perspectives of
      individuals with intellectual disabilities. Procedures and strategies employed to
      involve these individuals in the project were documented. Specifically, we
      describe the use of individual interviews and focus groups (e.g., purpose,
      rationale, facilitation techniques) to collect data, and verification meetings in
      which a prompting hierarchy and cueing were employed to assist participants in
      confirming or disconfirming the researchers' interpretations of the emerging
      findings. Highlights of the results were presented to illustrate the efficacy of
      the strategies in enabling the participants with intellectual disabilities to
      share their perspectives on social integration.

PMID- 10900930
TI  - Mental retardation and sentences for murder: comparison of two recent court
      cases.
AB  - Several states and the United States have laws that exempt persons who have
      mental retardation from the death penalty and other severe sentences. Two recent
      murder cases in Indiana, which has such a law, illustrate some of the problems in
      applying it. The characteristics of the two defendants were quite similar, but
      one defendant was found to have mental retardation and was exempted from the
      death penalty and the other was not. The disparity was attributed to differences
      in the assessment of adaptive behavior and to general stereotypes of people who
      have mental retardation. Equal application of sentencing limitation laws requires
      greater involvement of professionals with specialized training and experience in
      mental retardation.

PMID- 10900931
TI  - Anatomy of commitment: an in vivo study.
AB  - A self-evaluation of one small but innovative agency providing supported living
      and other community supports to individuals with developmental disabilities is
      presented. Key elements that appear to perpetuate a culture of commitment among
      direct support and supervisory staff are described. Agency staff people have
      achieved the capacity to listen and respond to individuals and honor their
      choices. In order to assure that individuals get what they need, staff members
      take appropriate initiative, work outside of their assigned hours, and support
      one another. Whereas most human service organizations function within the
      parameters of well-defined policies and procedures, the agency described here
      operates more flexibly. The observed pattern of organizational dynamism and
      reflexivity is compared to that of a living organism.

PMID- 10900932
TI  - Are people with intellectual disabilities just another customer? Interviews with
      business owners and staff.
AB  - Descriptive information on the views of business people towards the presence of
      persons with intellectual disabilities as customers was reported. We interviewed
      89 individuals representing a range of shops and local amenities in four urban
      and four country regions in Queensland, Australia. We also systematically
      examined the influence of degree of intellectual disabilities by interviewing
      employees in shops near community residential facilities for persons with
      mild/moderate and those near facilities for persons with severe/profound
      intellectual disabilities. A third group of businesses not located near any such
      residential facilities served as a control group. Overall, results suggest that
      business people had few special concerns related to interactions with customers
      who have intellectual disabilities.

PMID- 10900933
TI  - Rapid cycling bipolar disorder in individuals with developmental disabilities.
AB  - The assessment and treatment of the rapid-cycling variant of bipolar disorder in
      individuals with developmental disabilities is challenging. Outcomes are
      optimized by a long-term commitment to the establishment of objective monitoring
      systems by interdisciplinary teams. In this retrospective case series, we
      contrast the phenomenology, clinical outcomes, treatment responses, and clinical
      characteristics of 26 individuals with bipolar disorder and developmental
      disabilities, 12 with nonrapid cycling courses and 14 with rapid cycling courses.
      Similarities and differences are highlighted both within these two groups and in
      reference to published findings for individuals without disabilities.

PMID- 10900934
TI  - Group action planning as a support strategy for Hispanic families: parent and
      professional perspectives.
AB  - Focus group interviews were conducted to obtain participants' preliminary
      reactions to the responsiveness of group action planning, a person-centered
      planning approach, as a support strategy for Hispanic families of individuals
      with disabilities. Focus group participants were 38 Hispanic parents of
      youth/young adults with developmental disabilities and 22 professionals who
      provided support services to Hispanic youth/young adults with developmental
      disabilities and their families. Both constituency groups identified advantages
      and disadvantages of group action planning. We focus our key recommendations on
      the implications of this information for education and human service systems as
      well as directions for future research.

PMID- 10900935
TI  - Prevalence of dementia and impact on intellectual disability services.
AB  - In a statewide survey, dementia was found in 3% of adults age 40+; 6%, age 60+;
      and 12%, age 80+. Among adults with Down syndrome, the rates were 22% for adults
      age 40+ and 56% for adults age 60+. Observed onset occurred in the mid-60s (early
      50s for those with Down syndrome). Alzheimer-type dementia was the most frequent
      diagnosis. With the occurrence of dementia expected to rise proportionately with
      the increase of longevity among adults with intellectual disabilities, care
      systems will have to raise the "index of suspicion" among staff and families,
      become "dementia capable," and improve their diagnostic and technical resources,
      as well as their care management supports designed to prolong the "aging in
      place" of adults affected by dementia.

PMID- 10900936
TI  - Patterns in mortality over 60 years among persons with mental retardation in a
      residential facility.
AB  - Records of 2,444 decreased institutionalized persons with mental retardation were
      examined for etiologies, disabilities, causes of death, and life expectancies
      over 60 years. Participants at most risk tended to have prenatal etiology of
      brain damage, to be young, and have the lowest IQs, epilepsy, poor mobility and
      feeding skills, and more medical complications. Most mortality was from
      respiratory infections. Epilepsy was present in 57.2% but was rare in people with
      Down syndrome. Sudden death occurred in 22.2% of these deceased residents. Over
      the years generally more residents had prenatal etiology of mental retardation,
      lower IQ, epilepsy, and were nonambulatory and older when they died.

PMID- 10900937
TI  - Five-year trends in Medicaid institutional (ICF/MR) populations, home and
      community based services reflect major changes.

PMID- 10900938
TI  - [Combination of cisplatin and vinorelbin in the neoadjuvant treatment of locally
      advanced cervical carcinoma. Phase II study].
AB  - BACKGROUND: Aim of this phase II study is to evaluate the cytoreductive efficacy
      and the toxicity of a regimen consisting of cisplatin and vinorelbine as
      neoadjuvant chemotherapy for three cycles every 21 days in patients with locally
      advanced cervical carcinoma. METHODS: Between April 1996 and December 1998, 33
      untreated patients with locally-advanced cervical carcinoma received neoadjuvant
      chemotherapy with cisplantino 80 mg/m2 (day 1) plus vinorelbine 25 mg/m2 (day 1
      and 8). Within 28 days from completion of chemotherapy patients in complete or
      partial response were submitted to radical hysterectomy plus pelvic
      lymphadenectomy. RESULTS: Twenty-six patients (79%) were submitted to radical
      surgery; four patients were not submitted to surgery because of poor response to
      treatment, two for anesthesiological contraindications and one refused surgery.
      The combination of cisplatin plus vinorelbine in this phase II study induced a
      clinical overall response rate of 90%, with 8 pathologic complete response (24%).
      CONCLUSIONS: The association of cisplatin and vinorelbine as neoadjuvant
      chemotherapy in locally-advanced cervical carcinoma showed to be safe and
      effective with a low cost and poor toxicity.

PMID- 10900939
TI  - [Changes of the pulsatile index in ovarian and uterine arteries of infertile
      women. Case-control study].
AB  - BACKGROUND: This study was performed to evaluate the frequency of female
      pathology that cause infertility and to appraise the difference of pulsatility
      index in the ovarian and uterine arteries in infertile women and in a control
      group of healthy women. METHODS: In the period between January 1997 and March
      1999 52 infertile couples were examined carrying out an accuracy anamnesis and
      objective examination. The dosing of FSH, LH, estrogens, progesterone, and an
      ultrasound examination for each woman was required. The pulsatility index in the
      ovarian and uterine vases was calculated with the color Doppler technique.
      RESULTS: A female pathology caused infertility in 24 couples, where only in nine
      couples the cause was masculine. In 14 couples there was a pathology in both the
      partners. In 5 couples any pathology was identified. The median of pulsatility
      index in healthy women was 1.8. Variations were observed in all the women with
      ovarian or uterine pathology unless in those with uterine malformations. An
      increase of the pulsatility index was observed also in 3 couples in which any
      cause of infertility was identified. CONCLUSIONS: Female pathology is a very
      common cause of infertility. The evaluation of the pulsatility index in ovarian
      and uterine arteries can be useful diagnosing the cause of infertility and in to
      explain an infertility due to unknown cause.

PMID- 10900940
TI  - [Ovulation induction and the risk of ovarian tumors].
AB  - In the last years it has been observed a more and more increasing number of women
      submitted to therapies for induction of ovulation (disorders of the ovulation
      represent 33% of the causes of female infertility). In 1998, these therapies had
      been administrated to approximately two million of USA women. Various Authors
      have assumed a possible relationship between induction of ovulation and ovarian
      tumors. Between 1982 and 1997, at least 43 cases of ovarian tumors have been
      published (among these, there were also 25 cases of epithelial tumors) occurring
      in women previously treated with ovulation induction. The mean age of patient was
      30.3 years, approximately 20 years younger than normal patient population for the
      same tumors. Among the possible causes of epithelial ovarian tumors, there is the
      trauma of the ovary surface caused by the continuous repeating of the ovulation
      phenomenon (incessant ovulation). Gynecologist should be aware of this potential
      risk for their patients. Multicentric studies should be evaluated in order to
      establish the risk of ovarian cancer in women treated for infertility problems. A
      survey of the international literature is made in order to analyse the
      epidemiological studies and to discuss the relationship between ovulation
      inducing agents and ovarian tumors.

PMID- 10900941
TI  - [Role of pH as a regulator of vaginal physiological environment].
AB  - In the vagina there are several microorganisms. Their survival is fundamental to
      have a physiological environment in the vagina (ecosystem). The same vaginal
      environment playg a fundamental role to guarantee tho survival of resident
      microorganisms. Several factors, like changes of temperature and oxygenation, can
      interfere on vaginal ecosystem, but the resident vaginal microorganisms are the
      main factors to stabilize the vaginal ecosystem. The Doderlein's lactobacillus is
      the predominant vaginal microorganism. It is capable of fermenting the glycogen
      deriving from the decline of the eutrophic vaginal mmucosa, to lactic acid with
      release of hydrogen ions. The final result of that metabolism is an acid pH with
      values between 4-4.5. Vaginal pH undergoes physiologically changes from birth to
      menopause, according to changes of ovarian steroids occurring during woman's
      life. Adequate levels of estrogens play a fundamental role in the trophism of
      vaginal mucosa. In fact, estrogens increase the cellular content of glycogen.
      Exogenous acbvities on vaginal pH can be exerted by several factors, such as
      sexual activily, oral contraceptives, systemic diseases, vaginal infections
      (candidosis, thrichomonias, vaginosis), systemic or local therapies. They
      incrcase vaginal pH by acting through different mechanisms. The increase of
      vaginal pH is detrimental for the survival of Doderlein's lactobacillus, but not
      for the pathogenetic microorganisms whose replication, on the contrary, is
      favored by the absence of contraction exerted by Doderlein's bacillus. It has
      been showed that local acidifying substances (lactic acid, lactobacillus and
      substances recently synthesized like alpha-aminovalerianic acid, policarbophil
      and carbopol 934) are useful in restoring the biological and chemical
      characteristics of the vaginal ecosystem.

PMID- 10900942
TI  - [Intrauterine fetal death in twin pregnancy].
AB  - A case of twin pregnancy with intrauterine death of one foetus during the 19th
      week of pregnancy has been described and the obstetric approach is reported.
      Pregnancy was actively continued with the following procedure: 1. Tocolysis, 2.
      Anti-infective prophylaxis; 3. Monitoring of coagulation on factor; 4. Weekly
      echotomography. In the 39th week the baby was delivered by caesarean section. The
      baby was discharged in good health on the 5th day after delivery.

PMID- 10900943
TI  - Splenic involvement in ovarian cancer. Description of three cases.
AB  - Metastatic involvement of the spleen in patients with ovarian cancer is unusual.
      Solitary splenic metastasis in the absence of disseminated disease are rare.
      Three cases of advanced ovarian cancer with splenic involvement are reported. The
      splenectomy was adopted in two patients.

PMID- 10900944
TI  - [The physician's responsibility towards birth: ethical, deontological and legal
      aspects].

PMID- 10900945
TI  - [Sleep problems with fatal sequelae. Do you know the errors of your patients?].

PMID- 10900946
TI  - [Prevention of early summer meningoencephalitis. When should you vaccinate?.
      Interview by Dr. Beate Schumacher].

PMID- 10900947
TI  - [Sudden syncope in your patient. Harmless cardiovascular disorder or risk of
      sudden cardiac death?].

PMID- 10900948
TI  - [Asthma therapy in children. Value of long acting beta-mimetic drugs and anti
      leukotrienes].
AB  - In recent years, new therapeutic options have become available for the treatment
      of bronchial asthma in childhood. In children older than five years, long-acting
      beta mimetics are now an accepted medication, especially for severe forms of
      asthma or significant nocturnal symptoms. These new drugs should be prescribed
      only in combination with inhaled steroids. An effect of these beta mimetics on
      the inflammatory reactions underlying asthma is not to be expected. The second
      new therapeutic approach is the use of antileukotrienes, which are of particular
      help in children with a compliance problem vis-a-vis inhaled steroids, although
      their antiobstructive effect is weaker than that of beta mimetics or medium- or
      high-dose inhaled steroids. Whether the combination of these drugs with inhaled
      steroids can improve asthma control or reduce the use of steroids in children
      remains to be elucidated.

PMID- 10900949
TI  - [Steroids in COPD? Trial administration and subsequent discontinuing if not
      effective!].
AB  - Chronic obstructive pulmonary disease (COPD) should be strictly differentiated
      from bronchial asthma--even though, in particular after a lengthy course of
      illness, mixed forms are also to be seen in the doctor's office. Today, the
      treatment of choice for bronchial asthma is the use of inhalative
      glucocorticosteroids which, in the case of COPD, are only of secondary
      importance. In a poll we conducted, however, 18 out of 28 COPD patients in two
      pneumological centers in Frankfurt/Main, received a glucocorticoid, although only
      20% of these patients may be expected to respond positively to this form of
      treatment. A step-down-schema permitting an early check of whether a response to
      glucocorticoid is to be expected in COPD patients is proposed. Independently of
      this, however, 14-day treatment of acute exacerbations with glucocorticoids
      improved the results of treatment to a small, but clinically relevant, degree.

PMID- 10900950
TI  - [Asthma education for children and adolescents. 4 good reasons for program
      implementation].

PMID- 10900951
TI  - [Costly type 2 diabetes mellitus. Does diabetes cost 20 billion per year?].

PMID- 10900952
TI  - [Good digestion--essential for blood coagulation. Thrombosis ABC, 17: Vitamin K
      deficiency and konakion].

PMID- 10900953
TI  - [What comes before hyposensitization? Diagnostic series: Anamnesis--skin tests-
      provocation tests].

PMID- 10900954
TI  - [Travel apothecary for the physician. 4: The pill and insulin--caution with time
      delays!].

PMID- 10900955
TI  - [Efflorescence after infection. Immunothrombocytopenic purpura (Werlhof
      disease)].

PMID- 10900956
TI  - [Effect of implant geometry on strain distribution in peri-implant bone].
AB  - Recent developments and results in the field of mechanical bone stimulation have
      made it possible to define limits between physiological and non-physiological
      transmission of strength to the bone. Now it is necessary to investigate the
      different geometries of dental implants regarding biomechanical reliability. The
      aim of this study was to examine the distribution of strain on the bone along
      different basic forms of implants during loading using finite element analysis
      (FEA). The following implant designs were included in the study: cylinder,
      threaded cylinder, cylinder with steps, threaded cylinder with steps, and double
      disk implants. All implants had a length of 12 mm and a diameter of 4 mm, the
      axial loading was defined as 300 N. Threaded implants showed more homogeneous
      distribution of strain than stepped implants, however, the maximum values were
      below the physiological range. Shortening of the implants led to an increase of
      the values, however, there was a zone of hypophysiological strain apically. Disk
      implants showed extremely low values at the disk margins, possibly due to the
      lack of physiological bone stimulus by the disks. Overall, none of the implants
      showed optimal distribution of strain, even though homogeneous strain
      distribution is decisive for long-term implant stability.

PMID- 10900957
TI  - [Determining the size of the specific surface of bone substitutes with gas
      adsorption].
AB  - The surface area and the microporosity of bone regeneration materials influence
      their chemical and biological properties. Therefore, the size of the specific
      surface area and the distribution of the pore diameters (pores < 1 micron) of
      bone regeneration materials were analyzed within this study. The analyzed
      hydroxyapatites were of synthetic, bovine, and phytotroph origin. The tricalcium
      phosphates and the bioglasses included only synthetic materials. The gas
      adsorption of each specimen was analyzed using a volumetric N2/Kr system (ASAP
      2010, Micromeritics). Additionally, for materials with a specific surface area (>
      2 m2/g) the pore size distribution was evaluated by the BJH-method. Two of the
      materials evaluated astonishingly large dimensions of the specific surface area
      (BioOss 79.7 m2/g, Algipore new 14.6 m2/g). A medium surface area was found for
      Algipore old (4.9 m2/g) and Interpore200 (2.64 m2/g). All other included
      materials showed only small sizes of the specific surface area (Ceros80 1.8 m2/g,
      Ceros82 1.31 m2/g, Cerasorb 1.2 m2/g, Biobase 0.7 m2/g, Endobone 0.7 m2/g,
      Perioglas 0.6 m2/g, Allotropat50 0.23 m2/g, Biogran 0.2 m2/g). The materials with
      large and medium sizes of the specific surface area evaluated the following pore
      diameters: BioOss 2-50 nm, Algipore new 2-100 nm, Algipore old 5-50 nm,
      Interpore200 2-100 nm. Pore sizes less than 2 nm were not found in relevant
      numbers. The materials BioOss, old and new Algipore, and Interpore200 contain a
      large interconnecting mesopore system (diameter < 1 micron). For the materials
      Biobase, Endobone, Perioglas, Allotropat 50, and Biogran this cannot be assumed.
      The materials Ceros80, Ceros82, and Cerasorb evaluated a specific surface area
      between those and might include only a small part of these interconnecting pores.
      An influence of the interconnecting porosity and the different sizes of the
      specific surface areas on the biological behavior of the bone regeneration
      materials can be suggested.

PMID- 10900958
TI  - [Pathogen spectrum and resistance status of exclusively anaerobic odontogenic
      infections].
AB  - Out of 440 dentogenic pyogenic infections, 171 exclusively caused by anaerobes
      were investigated to understand the importance of anaerobic bacteria in dental
      pyogenic processes better. Grampositive anaerobic bacteria dominated. The
      predominant grampositive isolates in monoinfections were Peptostreptococci and in
      the case of mixed infections, strains of the genus Eubacterium. Strains of
      Prevotella and Porphyromonas dominated the gramnegative anaerobic spectra. The
      resistance to penicillin was very low. Altogether, only one strain of Prevotella
      oris and one strain of Prevotella oralis showed resistance to penicillin.

PMID- 10900959
TI  - [Comparative in vitro studies of self-boring and self-tapping screws.
      Histomorphological and physical-technical studies of bone layers].
AB  - Self-drilling screws are gaining increasing importance in maxillofacial surgery.
      This study assesses which screw design, self-drilling or self-tapping, is best
      suited to various locations of the human skull. With regard to different areas in
      the human midface, mandible, and cranium, the thickness of cortical bone varies
      as well as the relative proportion of cortical to cancellous bone. Criteria used
      to judge the success of screws were minimal insertion torque and minimum
      temperature, maximum pullout strength, and minimum deformation and destruction of
      the bone. To mimic the variations in anatomical conditions, 1-mm and 3-mm-thick
      cortical bone specimens and cancellous bone blocks were prepared. Eight screws of
      three types (self-tapping, self-drilling/self-tapping, conically shaped self
      drilling) were inserted into the different bone specimens. Torque and temperature
      were measured during the insertion procedure. Subsequently, the screws were
      carefully removed and the specimens were processed for histological evaluation.
      The same insertion protocol was used to test the pull-out strength of the screws.
      The conically shaped screw showed best results in cancellous bone for all
      parameters. The self-tapping screw with a pilot hole performed best in thick
      cortical bone and the self-drilling/self-tapping screw performed better than did
      the others in thin bone. The results suggest the three screw designs to be
      optimal for different locations of the human skull. This project provides the
      data for a planned in vivo study that will evaluate the long-term influence of
      deformation and temperature on stability and osseointegration of the screws.

PMID- 10900960
TI  - [Effect of positioning errors on magnification factors in the mandible in digital
      panorama imaging].
AB  - Magnification factors (VF) in relation to various head positions were evaluated
      for a digital panoramic radiography machine (Orthophos DS, Sirona) by means of a
      dry skull phantom. Six metallic objects were attached to the facial layer of the
      mandible. A set of 170 digital radiographs (program 1) was produced, with defined
      positioning errors within the vertical and horizontal plane. Repeated digital
      measurements of the object images were performed by one reader, applying the
      mouse-driven measurement tool integrated in the proprietary software. In
      addition, the central layer of the radiographic device was experimentally
      determined and its location compared to that of the accurately positioned dry
      mandible. All objects were located on the outside of the central layer of minimum
      distortion and therefore placed towards the sensor. One- and two-way analysis of
      variance was applied for the statistical evaluation of the data, with VF as
      dependent variable and the positions as factors, respectively. Vertical
      inclinations of the skull affected horizontal VF only in the premolar region (p =
      0.0069). However, when the skull was rotated within the horizontal plane, VF was
      significantly influenced in all anatomical regions of the mandible (p = 0.0001).
      This was particularly obvious in the premolar region, with a maximum variation of
      10.3%. Fluctuations of VF were more pronounced in the premolar region than at the
      mandibular angle. We conclude from this study that, as expected, digital
      panoramic radiographs exhibit identical distortion effects as compared to
      conventional panoramic x-rays. Exact quantification of regional magnification
      requires (spherical) reference objects with known dimensions. Horizontal
      magnification is quite unreliable and far less reproducible than vertical
      magnification. Whenever several panoramic radiographs of one patient are to be
      compared quantitatively, accurate positioning of the patients' head is a
      necessary prerequisite.

PMID- 10900961
TI  - [Clinical manifestations of CHARGE association in the area of the mouth, jaw and
      face].
AB  - Clinical experience of 11 patients with CHARGE association is reviewed. The study
      comprised six girls and five boys. All presented with congenital heart disease.
      Eight had bilateral choanal atresia. Coloboma affecting either one or both eyes
      was detected in nine children. Nine patients suffered abnormal pinnae or
      deafness. In addition to major abnormalities, further anomalies of the orofacial
      region and the upper airways occurred in all patients. All children exhibited
      velopharyngeal incoordination and swallowing problems often resulting in
      recurrent aspiration pneumonia. Three patients had cleft lip and palate. Both
      micrognathia and high-arched palate were present in two patients. Facial palsy
      was observed in six patients. Optimal management requires a multidisciplinary
      approach with active coordination and cooperation between the appropriate
      specialties. The anatomical repair of bilateral choanal atresia should be
      performed as early as possible. In our experience, the transpalatal approach is
      far more satisfactory than the transnasal. It gives the surgeon the opportunity
      of direct access and anatomical repair. After the child has grown stronger, a
      long-term management is desirable including developmental and feeding training.

PMID- 10900962
TI  - [Distraction osteogenesis of the mandible in craniofacial abnormalities].
AB  - In recent years, lengthening the human mandible by distraction osteogenesis has
      become an accepted treatment to correct severe mandibular hypoplasia. Using
      intraoral unidirectional and extraoral bidirectional distraction devices we
      report about our experiences and results in the application of the bone
      distraction technique in four selected cases of syndromal disease, including
      various forms of mandibular hypoplastic malformations. The patients involved were
      a boy with Pierre Robin syndrome, a girl with unilateral facial hypoplasia in
      Goldenhar's syndrome, a case with Nager's syndrome, and a rare case of midline
      deficiency caused by partial deletion of chromosome 18 (18p-syndrome). The
      distraction period lasted from 6 to 30 days and new bone formation, ranging from
      6 to 28 mm, was achieved.

PMID- 10900963
TI  - [Initial experiences with digital 3-dimensional stereophotogrammetry imaging].
AB  - A digitised three-dimensional (3-D) image of the face has many valuable uses.
      These include accurate measurements of facial morphology, clinical documentation
      and objective analyses of surgical procedures. A new system presented here, based
      on stereophotogrammetric techniques, instantaneously captures digitised images
      using high-resolution cameras. It has an accuracy of more than 0.5 mm RMS and
      creates the 3-D image from approximately 20,000 points. The principles of the
      image capturing are demonstrated and the potential uses discussed. Surgical
      changes of the soft tissue in two patients following orthognathic surgery are
      also illustrated. This new capturing and measurement system provides a simple
      method of determining 3-D changes in soft tissue following surgery and is a
      useful tool for clinical purposes.

PMID- 10900964
TI  - [Mandibular involvement in chronic recurrent multifocal osteomyelitis (CRMO) in
      adulthood].
AB  - A 42-year-old patient was admitted to our clinic with the diagnosis of primary
      chronic osteomyelitis of the mandible. Since the initial manifestation,
      approximately 9 months earlier, the patient had undergone numerous antibiotic
      treatment trials. Various tissue specimens exhibited no microbial growth.
      Computer tomography demonstrated severe sclerotic changes with partly osteolytic
      areas in the complete right horizontal ramus of the mandible. Decortication was
      carried out and both soft and hard tissue specimens were taken. Histological
      assessment revealed slightly sclerotic bone with reactive periosteal bone
      production, as in chronic non-specific osteomyelitis. Because of progressive pain
      and paresthesia, a 3-phase skeletal scanning was performed before the planned
      resection. In addition to an intensive labeling in the right mandible, further
      intensive lesions were found at the first right rib, the sternum, and the
      vertebral column. The subsequent magnetic resonance tomography confirmed the
      infiltration, as seen in osteomyelitis, in all these areas. Under the assumption
      of chronic recurrent multifocal osteomyelitis (CRMO), an immunosuppressive
      therapy with diclofenac and prednisolone was started, which at first brought
      about complete remission. As CRMO is very rare in our specialty, it might be
      suspected that it is the cause of some cases of primary therapy-resistant
      osteomyelitis. The importance of early diagnosis must be underlined, because
      therapy differs fundamentally from that of the more common bacterial
      osteomyelitis. A bone scan is therefore of great value in the diagnostic scheme
      of therapy-resistant osteomyelitis.

PMID- 10900965
TI  - [Management of comminuted and open fractures of the mandible and fractures in
      atrophic mandibles with titanium mesh].
AB  - Miniplate osteosynthesis is a standard method for the surgical treatment of
      mandible fractures today. Apart from easy handling, in the majority of cases it
      also ensures adequate fracture stability. The treatment of fractures of very
      atrophic mandibles as well as mandibular defects and comminuted fractures with
      miniplates and rigid plates is often difficult or only possible to an inadequate
      extent. Titanium mesh has proved successful for the treatment of such fractures.
      Compared with conventional miniplates this mesh is outstanding for its
      considerably higher stability due to its given geometry. The titanium mesh can be
      adapted and screwed individually in any situation, in contrast to miniplates and
      rigid plates. As a result, complications such as fracture gap infections and
      pseudoarthrosis can be avoided to a great extent.

PMID- 10900966
TI  - [In Process Citation]

PMID- 10900968
TI  - Pages from a sociometric notebook: an analysis of nomination and rating scale
      measures of acceptance, rejection, and social preference.

PMID- 10900967
TI  - Conceptualizing and measuring peer acceptance and rejection.

PMID- 10900969
TI  - Recent advances in measurement theory and the use of sociometric techniques.

PMID- 10900970
TI  - A ratings-based approach to two-dimensional sociometric status determination.

PMID- 10900971
TI  - Stability of sociometric categories.

PMID- 10900972
TI  - [Tuberculosis control in Russia on the eve of twenty first century].

PMID- 10900973
TI  - [Tuberculosis epidemiology and disease control in Uzbekistan].
AB  - The tuberculosis situation is complicated in Uzbekistan and in other countries of
      the world. In the past 5 years, due to the transition from mass prophylactic
      examinations to the differential surveys of population groups, the annual
      coverage of the population to be examined by fluorographic studies has reduced
      from 6 to 3.5 million along with a simultaneous rise in tuberculosis detection
      rates from 0.1 to 0.24% and in its incidence by 33.3%. Searches for new
      organizational forms of tuberculosis control work are under way. The State
      programme on tuberculosis control and the draft law of the Republic of
      Uzbekistan, which regulate associated measures have been developed.

PMID- 10900974
TI  - [Treatment of multidrug resistant tuberculosis in Santakiskes tuberculosis
      hospital].
AB  - The authors studies 98 patients (82 males and 16 females) in 1994-1996. The
      patients were found sputum Mycobacteria tuberculosis (MT) resistant to two
      essential antituberculosous drugs: isoniazid and rifampicin. In 67 (68.4%) cases
      MT resistance was verified in other laboratories of the country. The examinees
      were 13 new cases and 17 had relapses. Sixty eight patients were diagnosed as
      having chronic tuberculosis. After multidrug resistant strains were identified,
      the patients were treated by an individual regimens by choosing adequate drugs
      from different groups. Twenty patients were operated on. Sputum conversion
      occurred in only 24 (24.5%) patients. In 14 of them clinical and X-ray lesion
      disappeared. In 74 (75%) good treatment outcomes were not achieved and MT
      remained in the sputum. There were statistically significant differences in the
      treatment outcomes among new, relapsing, and chronic cases (poor treatment
      outcomes were in 38.5, 64.7, and 85.3%, respectively). The surgical outcomes
      proved to be no better than those in drug-treated patients due to the incorrect
      definition of indications for surgery or advanced disease. The findings show that
      the outcomes were poor in chronic MT multidrug-resistant patients and fair
      results could be achieved in new cases of the disease diagnosed in time.

PMID- 10900975
TI  - [Impact of tuberculosis patient's attitude towards their disease on therapeutical
      efficiency].
AB  - The paper analyzes the factors that form the types of the patients' feelings of
      their disease and provides evidence for the impact of their attitude towards the
      disease on treatment outcomes. The paper gives a prognostic table for early
      determination of whether the patients can stop their therapy ahead of schedule.

PMID- 10900977
TI  - [Lung and mediastinum puncture under ultrasound guidance].
AB  - Based on their own experience with punctures under the guidance of ultrasound
      study of the bulky formations of the lung and mediastinum in 254 patients, the
      authors show the potentialities of this technique. The paper describes the
      technique and its efficiency, shows difficulties and possible complications due
      to its use.

PMID- 10900976
TI  - [Clinical pattern of tuberculosis in patients with mental disorders in Sverdlovsk
      region].
AB  - The clinical pattern was first studied in 153 new cases of tuberculosis with
      mental disorders. Most patients were admitted from psychoneurological boarding
      houses. Prophylactic survey revealed tuberculosis in most patients. There were
      prevalent infiltrative and focal forms of a specific process. Proper therapy
      provided benefits in the majority of patients. However every six patients had
      worsening tuberculosis.

PMID- 10900978
TI  - [Efficiency of shorter chemotherapy courses for intrathoracic tuberculosis in
      children].
AB  - To develop differential chemotherapy regimes for intrathoracic tuberculosis in
      children aged 3-12 years, 255 children with active tuberculosis underwent
      clinical and X-ray examination. Of them, 120 children received shorter
      chemotherapy in an early intensive phase by using three drugs (isoniazid,
      rifampicin, and pyrazinamide supplemented by streptomycin) in complicated
      tuberculosis. A control group (n = 135) had therapy without pyrazinamide. Shorter
      courses of therapy were shown not only to reduce total treatment duration on an
      average to 6.4 and 9.2 months in uncomplicated and complicated tuberculosis,
      respectively, but to contribute to more perfect healing processes and resolution
      of abnormal changes in 85.3 and 60.0% of children with uncomplicated and
      complicated forms, respectively. At the same time shorter treatment is well
      tolerated. It shows much fewer side effects than does longer treatment (20 and
      36%). There are no increases in the incidence of recurrent tuberculosis late at
      follow-up (2.7 and 2.7%, respectively).

PMID- 10900979
TI  - [New cases of pulmonary tuberculosis treatment within DOTS strategy].
AB  - Treatment outcomes were analyzed in 216 patients of whom 119 patients received
      the DOTS treatment, 97 had conventional therapy. No bacterial isolation was found
      in 88% of patients, decay cavities became closed in 61%. Due to the DOTS therapy,
      sputum conversion was achieved in 93% of cases, no Mycobacteria tuberculosis
      being found in 70.2% of cases after 2-month therapy. Decay cavities could not be
      identified in 80% by the end of chemotherapy.

PMID- 10900980
TI  - [Fenazide efficiency in combined chemotherapy of new and relapsing pulmonary
      tuberculosis].

PMID- 10900981
TI  - [Use of systemic immunomodulator xymedone in distructive pulmonary tuberculosis].
AB  - The study was undertaken to examine 59 patients with destructive pulmonary
      tuberculosis who had T-cell dysfunction (loss of CD3+, CD4+, lymphocytes,
      slightly positive tuberculin test) and augmented IgA and IgG production. Oral
      Xymedone given in a dose 2.0 g daily for two 2 months in combination with
      antibacterial therapy abolished lymphopenia, restored CD4+ counts, CD4+/CD3+
      ratio, upregulated IgG levels, but did not affect IgA levels. The Xymedone
      treated patients developed fewer side effects due to basic antibacterial
      chemotherapy and showed more rapid culture conversion, resolution of pulmonary
      infiltration and closure of destructive cavities.

PMID- 10900982
TI  - [Surgical treatment of patients with advanced bilateral destructive pulmonary
      tuberculosis].
AB  - The paper analyzes the outcomes of surgical treatment of 135 patients operated on
      at the Surgery Clinic of the Institute. A set of surgical techniques, including
      pulmonectomy, collapsosurgical interventions, local cavernous exposures,
      thoroscopic surgery, thoracic caustic under artificial pneumothorax, was applied.
      The used system of surgical treatment was found to be beneficial for these
      patients, as confirmed by fewer surgical (3.0%) and postoperative (7.8%)
      complications, lower postoperative mortality rates (2.2%), and steady state
      clinical recovery in 91% and working capacity restoration in 76%.

PMID- 10900983
TI  - [Tuberculous spondylitis complicated by spinal disorders: diagnosis and
      treatment].
AB  - Complex diagnosis using additional radiation procedures (computed tomography and
      magnetic resonance imaging) for tuberculous spondylitis complicated by spinal
      disorders was made in 52 patients. It made the genesis of spinal cord disorders
      more clear. The genesis was due to epidural abscess, necrotic osseous tissue and
      bony compression of destroyed vertebrae. Spinal cord structural changes were
      detectable in the postoperative period. Hemosorption in combination with blood
      ultraviolet radiation was used in 25 (40%) patients for their indications, which
      allowed all the patients to be operated on. Surgical treatment of 60 patients by
      using radical interventions into the target site and extended corporolateral
      decompression of the spinal cord, by employing autograft spondylolodesis resulted
      in rehabilitation in 95% of cases.

PMID- 10900984
TI  - [Cytokine production-adenosine deaminase activity relationship in pulmonary
      tuberculosis].
AB  - The serum activity of the enzyme adenosine desaminase (ADA) was studied in
      patients with infiltrative tuberculosis in relation to IL-1 beta, TNF-alpha, IL-2
      productions, the magnitude of a lymphocytic proliferative response to PPD and
      PGA. There was an association of high ADA levels with the severity of a
      tuberculous process, with the least IL-2 production together with drastically
      increased IL1 beta and significant disorders in the TNF-alpha system. Moderate
      ADA increases reflect the regularly enhanced activity of immunocompetent cells in
      response to an infectious agent. The findings indicate that a simple biochemical
      test may be used for rapid preliminary evaluation of the severity of disease and
      immune performance.

PMID- 10900985
TI  - [Use of soluble ozone in combined treatment of pulmonary tuberculosis: lipid
      peroxidation and blood antioxidative defense systems].
AB  - Changes in lipid peroxidation and blood antioxidative defense systems and red
      blood cell function were studied in 16 patients with prolonged progressive
      pulmonary tuberculosis in response to intravenous soluble ozone (SO)
      administration. There was a drastic rise in the activity of intraerythrocytic
      superoxide dismutase (SOD) and a reduction in intracellular malonic dialdehyde
      (MDA) levels. In the remaining patients, there was a decrease in the activity of
      SOD and an increase in intraerythrocytic MDA concentrations. Plasma catalase
      activity increased in all patients and MDA levels lowered. It is proposed that
      initial SO doses for patients with chronic pulmonary tuberculosis should be
      chosen on an individual basis by taking into account intraerythrocytic SOD-MDA
      changes due to SO initiation.

PMID- 10900987
TI  - [Central hemodynamics in pulmonary tuberculosis patients at reoperation].
AB  - Central hemodynamic parameters were studied in 12 phthisiopulmonological patients
      by integral rheography before, at the end, and 1, 2, 3, 7 days after surgery.
      Signs of cardiovascular failure with phenomena of "blood flow centralization"
      were revealed. With intensive care, these hemodynamic changes were most prominent
      on days 1, 2, and 3 after surgery and hemodynamic improvement occurred on day 7.

PMID- 10900986
TI  - [Indices of mycobacterium tuberculosis growth in culture media and levels of
      active-phase proteins in different forms of pulmonary tuberculosis].
AB  - The relationship was examined between the bacteriological (growth time, the count
      of M. tuberculosis colonies) and biochemical (serum haptoglobin and ceruloplasmin
      levels) indices that characterize the magnitude of inflammation in 653 patients
      with different forms of pulmonary tuberculosis. Diagnostically, there was a
      dissimilarity in the biochemical indices studied and there was a stronger
      relationship between the bacteriological indices and haptoglobin levels.

PMID- 10900988
TI  - [Priorities in organization of postgraduate training of phthisiologists].

PMID- 10900989
TI  - [On the concept of Russian National Tuberculosis Control Program].

PMID- 10900990
TI  - Helping construct desirable identities: a self-presentational view of
      psychotherapy.
AB  - The author reviews the research demonstrating not only that clients withhold
      personal information and reactions from their therapists but also that such
      discretion is associated with positive therapy process ratings and outcomes.
      These results run counter to traditional approaches to psychotherapy, which
      demand a high degree of openness from clients. These puzzling findings can be
      explained by conceptualizing psychotherapy as a self-presentational process,
      wherein clients come to benefit from therapy by perceiving that their therapists
      have favorable views of them. Creating these favorable impressions can involve
      clients' hiding some undesirable aspects of themselves from their therapists. The
      author offers findings from the psychotherapy and social-psychology literatures
      in support of this view and makes suggestions concerning what clients and
      therapists might optimally reveal in therapy.

PMID- 10900991
TI  - Client concealment and self-presentation in therapy: comment on Kelly (2000)
AB  - The authors disagree with A. E. Kelly's (2000) conclusions that clients conceal
      things from therapists primarily for self-presentational reasons and that client
      concealment is positively related to positive therapy process and outcome. They
      also disagree with A. E. Kelly regarding the implications of self-presentation
      theory for therapy. Their review of the research suggests that clients do not
      conceal much from therapists, that what they do conceal involves many different
      kinds of information hidden for many different reasons, that therapists have wide
      variability in being able to detect hidden client material, and that the
      relationship of client concealment and therapist awareness of client concealment
      with therapy process and outcome is not clear. Finally, the authors discuss their
      views about implications of client concealment and self-presentation for therapy.

PMID- 10900993
TI  - A self-presentational view of psychotherapy: reply to Hill, Gelso, and Mohr
      (2000) and to Arkin and Hermann (2000)
AB  - The self-presentational view of psychotherapy challenges current assumptions
      about the benefits of high levels of clients' openness in therapy (A. E. Kelly,
      2000). The author responds to questions about whether clients' discretion really
      is linked to favorable therapy process ratings and outcomes. She also addresses
      problems that may emerge if readers apply a narrow definition of self
      presentation as a form of deliberate manipulation, rather than the intended
      definition of consciously or unconsciously showing oneself to be a particular
      kind of person for audiences. A brief review of the evidence on the role of
      audience feedback in self-concept change is offered, along with suggestions for
      explaining self-concept change to clients. The author concludes by clarifying and
      reasserting her suggestion that it is acceptable for clients to reveal the themes
      as opposed to details of their problems that seem particularly heinous or
      humiliating.

PMID- 10900992
TI  - Constructing desirable identities--self-presentation in psychotherapy and daily
      life: comment on Kelly (2000)
AB  - A. E. Kelly's (2000) thesis that psychotherapy clients benefit from withholding
      negative information is considered in light of current social-psychological
      theory and research. Positive illusions about oneself are associated with indexes
      of mental health; this is consistent with treating therapy as positive identity
      development. Self-presentation can shape self-concept, even apart from the
      feedback that an audience might provide; the social construction of identity is a
      powerful process, suggesting that withholding negative and presenting only
      positive information is adaptive. However, evidence concerning the level of
      identification of one's actions suggests complexities in understanding ways
      clients might deal with disclosing negative information; the authors argue that
      the impact on self-concept is probably more complex than A. E. Kelly's
      characterization and that the implications are of a broader scope than indicated
      so far.

PMID- 10900994
TI  - The effects of psychological therapies under clinically representative
      conditions: a meta-analysis.
AB  - Recently, concern has arisen that meta-analyses overestimate the effects of
      psychological therapies and that those therapies may not work under clinically
      representative conditions. This meta-analysis of 90 studies found that therapies
      are effective over a range of clinical representativeness. The projected effects
      of an ideal study of clinically representative therapy are similar to effect
      sizes in past meta-analyses. Effects increase with larger dose and when outcome
      measures are specific to treatment. Some clinically representative studies used
      self-selected treatment clients who were more distressed than available controls,
      and these quasi-experiments underestimated therapy effects. This study
      illustrates the joint use of fixed and random effects models, use of pretest
      effect sizes to study selection bias in quasi-experiments, and use of regression
      analysis to project results to an ideal study in the spirit of response surface
      modeling.

PMID- 10900995
TI  - Self-monitoring: appraisal and reappraisal.
AB  - Theory and research on self-monitoring have accumulated into a sizable literature
      on the impact of variation in the extent to which people cultivate public
      appearances in diverse domains of social functioning. Yet self-monitoring and its
      measure, the Self-Monitoring Scale, are surrounded by controversy generated by
      conflicting answers to the critical question, Is self-monitoring a unitary
      phenomenon? A primary source of answers to this question has been largely
      neglected--the Self-Monitoring Scale's relations with external criteria. We
      propose a quantitative method to examine the self-monitoring literature and
      thereby address major issues of the controversy. Application of this method
      reveals that, with important exceptions, a wide range of external criteria tap a
      dimension directly measured by the Self-Monitoring Scale. We discuss what this
      appraisal reveals about with self-monitoring is and is not.

PMID- 10900996
TI  - Culpable control and the psychology of blame.
AB  - A culpable control model is advanced to describe the conditions that encourage as
      well as mitigate blame and to assess the process by which blame and mitigation
      occur. The fundamental assumptions of the model are that evidence concerning
      harmful events is scrutinized for its contribution to personal control and
      spontaneously evaluated for its favorableness or unfavorableness. Spontaneous
      evaluations encourage a blame-validation mode of processing in which evidence
      concerning the event is reviewed in a manner that favors ascribing blame to the
      person or persons who evoke the most negative affect or whose behavior confirms
      unfavorable expectations. The author delineates the elements of perceived control
      and then discusses spontaneous evaluation influences on control and blame
      assessments. The blame-validation process is described next. Finally, the
      culpable control model is compared with extant theories of blame and
      responsibility and its basic tenets summarized.

PMID- 10900997
TI  - Sexual orientation and handedness in men and women: a meta-analysis.
AB  - Recent findings suggest that sexual orientation has an early neurodevelopmental
      basis. Handedness, a behavioral marker of early neurodevelopment, has been
      associated with sexual orientation in some studies but not in others. The authors
      conducted a meta-analysis of 20 studies that compared the rates of non-right
      handedness in 6,987 homosexual (6,182 men and 805 women) and 16,423 heterosexual
      (14,808 men and 1,615 women) participants. Homosexual participants had 39%
      greater odds of being non-right-handed. The corresponding values for homosexual
      men (20 contrasts) and women (9 contrasts) were 34% and 91%, respectively. The
      results support the notion that sexual orientation in some men and women has an
      early neurodevelopmental basis, but the factors responsible for the handedness
      sexual orientation association require elucidation. The authors discuss 3
      possibilities: cerebral laterality and prenatal exposure to sex hormones,
      maternal immunological reactions to the fetus, and developmental instability.

PMID- 10900999
TI  - [Advantages and deficiencies of the current classification of lymphomas].

PMID- 10900998
TI  - Sex differences and similarities in job attribute preferences: a meta-analysis.
AB  - Many researchers have studied sex differences in job attribute preferences. The
      authors meta-analyzed 242 samples collected from 321,672 men and boys and 316,842
      women and girls in the United States between 1970 and 1998. Findings indicated
      significant (p < .05) sex differences on 33 of 40 job attribute preferences
      examined. The effect sizes were small. Of the 33 significant differences, 26 had
      average effect sizes of magnitude .20 or less. The directions of the differences
      were generally consistent with gender roles and stereotypes. Many job attributes
      became relatively more important to women and girls in the 1980s and 1990s
      compared with the 1970s, indicating that women's aspirations to obtain job
      attributes rose as gender barriers to opportunity declined.

PMID- 10901000
TI  - [Stents in the urinary system].

PMID- 10901001
TI  - [Infection after orthotopic liver transplantation: analysis of the first 120
      consecutive cases].
AB  - OBJECTIVE: To report the infectious complications and presentation time of the
      first 120 consecutive liver transplants performed at our institution. METHODS:
      Prospective study of infectious complications among 120 consecutive adult
      patients who received orthotopic liver transplantation at Hospital de Cruces,
      from February 1996 to November 1998. Two patients received a renal transplant
      concomitantly. The same surveillance protocols were used for all patients and the
      criteria used to define infections were those reported by other authors. RESULTS:
      The group consisted of 120 patients, 95 males and 25 females. The age ranged from
      20 and 66 years (mean: 54 +/- 9 years). The indications for transplantation
      included alcoholic cirrhosis (47%), HCV cirrhosis (20%), hepatocellular carcinoma
      (17.5%), fulminant hepatitis (6%), primary biliary cirrhosis (2.5%) and
      miscellaneous conditions (7%). Three patients required retransplantation. Acute
      rejection was histologically diagnosed in 38 patients (31%). None of the patients
      had corticosteroid-resistant rejection. Fifty-one patients (42.5%) developed 76
      episodes of severe infection, which included: 48 episodes of bacterial infection
      among 33 patients (27.5%), tuberculosis in 7 patients (6%), 9 episodes of fungal
      infection among 8 patients (7%) and cytomegalovirus (CMV) infection among 8.5% of
      patients. No patient developed Pneumocystis carinii pneumonia. Fifteen (12.5%)
      patients died: six (12.5%) with active infection, and in four of them the
      infection was considered the cause of death. CONCLUSIONS: Infection rates due to
      bacteria and fungi were similar to those reported in the literature. A high rate
      of tuberculosis was found, which possible correlated with the high incidence of
      this disease in the general population. The low incidence of CMV infection was
      probably due to the preemptive therapy with gancyclovir. Trimethoprim
      sulfamethoxazol prophylaxis against Pneumocystis carinii was highly effective.

PMID- 10901002
TI  - [Retrospective study of early readmissions at an internal medicine service].
AB  - OBJECTIVE: To determine the frequency of hospital re-admissions to an Internal
      Medicine Department at a Community General Hospital as well as variables
      associated with them. METHODS: Analysis of hospital discharges during 1997. Data
      were provided by the Coding and Filing Service, and included sociodemographic
      data and aspects related to medical care to each patient, as well as discharge
      DRF according to the HCFA version. A logistic regression model was developed to
      identify variables independently associated with early re-admission risk (less
      than 30 days after discharge). RESULTS: The rate of early re-admission was 7.4%.
      The variables associated with a higher risk of admission included age, a hospital
      stay longer than the mean at first admission, and AIDS-associated conditions and
      heart diseases as main discharge diagnoses. CONCLUSIONS: Based on our data, we
      cannot consider the readmission rates as a reliable index in itself to be
      assessed negatively, as some re-admissions come unexpectedly and/or are
      unavoidable.

PMID- 10901003
TI  - [Incidence of type 1 diabetes mellitus in the Canary Islands (1995-1996).
      Epidemiologic Group of the Canary Society of Endocrinology and Nutrition].
AB  - OBJECTIVE: To prospectively evaluate the incidence of type 1 diabetes mellitus in
      patients up to 30 years of age in the Canary Islands during 1995 and 1996.
      PATIENTS AND METHODS: The population under study consisted of 744,444 inhabitants
      in the 0-29 year old group and 302,293 in the 0-14 year old group. The capture
      recapture method was used for estimating the probability of ascertainment.
      Hospital records and endocrinologists' reports were the primary source, whereas
      reports from the Canary Diabetes Association reports and sales of blood glucose
      monitors were the secondary source. RESULTS: A total of 223 new cases of type 1
      diabetes mellitus were detected during the study period. The degree of
      ascertainment was 90.1%. The observed incidence rates were 23.2 per 100,000 per
      year for the 0-14 year old group and 9.2 per 100,000 per year for the 15-29 year
      old group. The overall incidence rate was 15 per 100,000 per year for the entire
      group. The highest incidence was found in the 10-14 year old group. The incidence
      in males was higher than in females, and particularly significant in the 15-29
      year old group. No seasonal onset pattern was detected. CONCLUSIONS: A high rate
      of incidence of type 1 diabetes mellitus was observed in this study in children
      aged less than 15 years living in the Canary Islands.

PMID- 10901004
TI  - [Program for the substitution of therapeutic equivalents in the hospital
      setting].
AB  - BACKGROUND: A Program of Therapeutic Equivalents (TEP) is here reported which was
      elaborated and is currently in force at a third level university teaching
      hospital. MATERIALS AND METHODS: Therapeutic equivalents were selected within the
      same pharmacologic group on the basis of approved indications and both efficiency
      and safety data. RESULTS: TEP considers: a) the substitution of drugs which are
      considered therapeutic equivalents; b) withdrawal of drugs which have not proved
      efficiency or are of no interest for inpatients; c) continuation of therapies
      when changes are not advisable, and d) indistinct use of homologous drugs. From
      August 1998 up to April 1999, TEP was applied in 505 occasions; it was accepted
      in 499 (99%) and rejected in 6 (1%). DISCUSSIONS: The substitution of therapeutic
      equivalents should be viewed in the context of selecting the most appropriate
      drugs to be used in the hospital setting. TEP should be a consensus document and
      supervised by the Pharmacy and Therapeutics Commission.

PMID- 10901005
TI  - [Hearing loss and human immunodeficiency virus infection. Study of 30 patients].
AB  - OBJECTIVE: To asses hearing loss in patients infected with the human
      immunodeficiency virus (HIV) and its relationship with clinical stage
      (fulfillment of diagnostic criteria for human acquired immunodeficiency
      syndrome/AIDS) and degree of lymphocyte depletion (number of CD4+ lymphocytes).
      METHODS: Assessment of thirty consecutive HIV-infected patients regarding the
      presence of subjective hearing loss, pure-tone audiometry, brain stem auditory
      evoked potentials (BAEP); and number of CD4+ lymphocytes and treatment with
      antiretroviral drugs. RESULTS: Forty percent of patients reported hearing loss;
      33% had an abnormal audiometry and BAEPs were abnormal in 56% of patients. The
      most common findings included high-frequency sensorineural loss and an increase
      in the wave III latency and interaural I-V difference. Subjective hearing loss
      and an abnormal audiometry were both related to the administration of
      antiretroviral drugs, whereas abnormal BAEPs were related to AIDS and low CD4+
      lymphocyte counts. CONCLUSIONS: In HIV infected patients, an abnormal BAEP is the
      most common audiologic disorder, particularly in the advanced stages of the
      disease.

PMID- 10901006
TI  - [Multicentric Castleman disease versus systemic/cutaneous plasmacytosis, 2
      different names for the same process?].

PMID- 10901007
TI  - [A 66-year-old male with dysphagia and sudden thoracic paresthesia].

PMID- 10901008
TI  - [Vasculorenal arterial hypertension in a young male].

PMID- 10901009
TI  - [Abnormal mobility of the arms].

PMID- 10901010
TI  - [Costal lysis in a 58-year-old male].

PMID- 10901011
TI  - [Hypertensive elderly patient with pulsatile acousma and unilateral otorrhagia].

PMID- 10901012
TI  - [Bronchiolitis obliterans with focal organizing pneumonia and amiodarone].

PMID- 10901013
TI  - [Descending necrotizing mediastinitis of uncertain origin].

PMID- 10901014
TI  - [Transient changes in the atrioventricular conduction as the only manifestation
      of Lyme disease].

PMID- 10901015
TI  - [Autoimmune thrombopenia associated with Epstein-Barr virus infection].

PMID- 10901016
TI  - [Pneumococcal cavitating pneumonia in human immunodeficiency virus infection].

PMID- 10901017
TI  - [Is Steinert myotonic dystrophy a frequent cause of complete atrioventricular
      blockade?].

PMID- 10901018
TI  - [A century of research on rheumatoid arthritis. From empirical treatment to the
      development fo specific drugs].

PMID- 10901019
TI  - [History of rheumatoid arthritis].

PMID- 10901021
TI  - [Rheumatoid arthritis. Epidemiology. Etiologic factors].

PMID- 10901020
TI  - [Socioeconomic impact of rheumatoid arthritis].

PMID- 10901022
TI  - [Rheumatoid arthritis. Genetics and histocompatibility].

PMID- 10901024
TI  - [Methods of clinical evaluation of rheumatoid arthritis].

PMID- 10901023
TI  - [Pathogenesis of rheumatoid arthritis].

PMID- 10901025
TI  - [Clinical joint manifestations of rheumatoid arthritis].

PMID- 10901027
TI  - [Infective complications of rheumatoid arthritis].

PMID- 10901026
TI  - [Extra-articular manifestations of rheumatoid arthritis].

PMID- 10901028
TI  - [Juvenile chronic arthritis].

PMID- 10901030
TI  - [Radiology in rheumatoid arthritis].

PMID- 10901029
TI  - [Laboratory and synovial fluid in rheumatoid arthritis].

PMID- 10901031
TI  - [New imaging techniques in the diagnosis and follow-up of rheumatoid arthritis].

PMID- 10901032
TI  - [Prognosis markers and therapeutic approach in rheumatoid arthritis].

PMID- 10901033
TI  - [Local treatment of rheumatoid arthritis].

PMID- 10901034
TI  - [Medical treatment: delayed-action drugs, immunosuppressor agents, and combined
      treatments in rheumatoid arthritis].

PMID- 10901035
TI  - [Rheumatoid arthritis. Biologic treatments].

PMID- 10901036
TI  - [Leflunomide: a new treatment for an old disease].

PMID- 10901037
TI  - [Surgical treatment of rheumatoid arthritis].

PMID- 10901038
TI  - [Appropriate disposal of medical wastes--according to the manual on disposal of
      infectious wastes].
AB  - Medical organizations are responsible for appropriate disposal of their wastes.
      This paper explains the regulatory bases and management systems applicable to
      medical wastes as specified by the Ministry of Health and Welfare's manual on the
      disposal of infectious wastes.

PMID- 10901039
TI  - [Present status of nosocomial infections and biohazard of medical waste].
AB  - Nosocomial infections are already major problems and are a growing concern to all
      medical staff and among the general public. Therefore, an effective infection
      control program, especially against transmission mode of infection, is essential
      for the well-being of the patients and the safety of hospital personnel. Various
      categories of medical waste should be segregated adequately and appropriate
      management(treatment and disposal) is necessary. Adequate handling techniques can
      protect personnel from injury(occupational infection), and the biosafety manual
      should be available to prevent injury.

PMID- 10901040
TI  - [Introduction to sterilization and disinfection of medical wastes contaminated
      with human virus].
AB  - In this paper, we describe sterilization and disinfection of medical wastes
      contaminated with blood borne-virus, such as Ebola virus, Marburg virus, Crimean
      Congo hemorrhagic fever virus, Lassa virus, Hepatitis B virus and Human
      immunodeficiency virus.

PMID- 10901041
TI  - [Proper disposal(management) of medical wastes--management of medical waste at
      University Hospital attached to School of Medicine, Nagasaki University].
AB  - University hospitals, not only provide medical care but also perform education
      and research activities. The waste at university hospital differs from waste at
      another medical institutions. Because there are various kinds of waste containing
      toxic chemical substances and recombinant DNA, care should be taken in treating
      such waste.

PMID- 10901042
TI  - [Proper disposal(management) of medical wastes--infection prevention and waste
      management(Clean Hospital Project) at Hiroshima City, Asa Hospital].
AB  - Hospitals are socially obligated to maintain a clean environment and to dispose
      of medical waste, in order to prevent pollution and infection within and near the
      hospital. Since its establishment, Hiroshima City, Asa Hospital has been
      implementing a "Clean Hospital Project", which has two goals: infection
      prevention and waste management. The nosocomial infection prevention committee
      and medical waste treatment and disposal examination committee lead these
      efforts.

PMID- 10901043
TI  - [Proper disposal(management) of medical wastes--appropriate handling and disposal
      of medical wastes from pathology laboratories].
AB  - The appropriate handling and disposal of medical wastes from pathology
      laboratories were reviewed. Emphasis was placed on basic ideas regarding 1) the
      reduction of the total volume of the wastes and prevention of unnecessary waste
      production, and 2) laboratory practices friendly to the global environment. An
      ethical perspective is needed for the disposal of human organs and tissues.
      Evaporation-assisted reuse of organic solvents and formaldehyde, and filter
      adsorption of carcinogenic substances such as diaminobenzidine and ethidium
      bromide are also described.

PMID- 10901044
TI  - [Proper disposal(management) of medical wastes--the appropriate management of
      medical waste in laboratory].
AB  - In accordance with "The Manual for Management of Infectious Waste" which is based
      on the "Waste Management Law", a counterplan for the appropriate management of
      medical waste must be carried out in every hospital. This requires establishing
      "a committee for the appropriate management of medical waste" and to assign a
      "responsible person for management of medical waste" (an administrator for
      managing industrial waste under special control) inside the hospital. Since the
      law requires hospitals to take responsibility for discharging medical waste,
      hospitals must adopt a prudent policy for waste management. It becomes a most
      critical issue for hospitals, because medical waste is the subject of spot
      inspection under the supervision of MHW, and also the subject of border
      transgression prohibition between countries(both import and export) by the Bazel
      Treaty (1989) that Japan ratified in 1993. In this study, we discuss medical
      waste management in the central laboratory based upon the counterplan for
      appropriate management of medical waste at our hospital.

PMID- 10901045
TI  - [Present state of the medical waste disposal industry. Self-regulation and trends
      of the industry for future].
AB  - After the "Waste Disposal Act" was revised in 1991, only some medical wastes were
      legally recognized as "infectious wastes". For that reason, the disposition of
      medical wastes has been formally regulated. Despite the revision in the law, the
      system of medical waste disposal from medical facilities discharging medical
      wastes and disposers receiving the waste, is clearly deficient. That system is
      formally well-regulated, but not substantial. Especially according to some actual
      reports, there are many confusing problems, for example, the licensing standards
      are unclear, the disposition method involves inadequate incineration and
      sterilization, and there is no plan for safe collection and safe transportation
      of medical wastes. The more seriously we consider adequate disposal methods for
      medical wastes, the more we realize how difficult it is to find a solution to
      these problems.

PMID- 10901046
TI  - [Selection guide of incinerator on medical organizations].
AB  - A countermeasure to dioxin is implementation of the so-called "3T" principle
      (Temperature, Time, Turbulence), and prevent re-synthesis of dioxin in the
      treatment process of exhaust gas. To prevent dioxin re-synthesis, the temperature
      of exhaust gas after exiting incinerator should immediately be cooled to less
      than 200 degrees C, and the dust in the exhaust gas should be removed by a high
      quality collector. As the exhaust gas contains a high concentration of HCl, the
      selection of materials to treat the exhaust gas should be carefully considered.

PMID- 10901047
TI  - [Alternative technologies on infectious waste treatment, and guidelines for
      evaluation on safety and efficacy of the alternative technologies].
AB  - Recently, regulations on incinerators have been tightened, the number of
      incinerators in medical facilities has hastily decreased. Under these
      circumstances, alternative technologies for medical waste treatments that can be
      substituted for incinerators have received considerable attention. Many
      alternative technologies for treating medical wastes have already been installed
      in many facilities in advanced nations such as United States of America, Europe
      and Australia. Appropriate guidelines are essential for safe treatment of medical
      wastes, and hence some guidelines for evaluation of the safety and efficacy of
      the alternative technologies have been established in advanced nations including
      Japan. In this chapter, a summary of alternative technologies, recent regulations
      worldwide on the technology and an outline of the guidelines are described.

PMID- 10901048
TI  - [Proposals on the management of the wastes from the home health care].
AB  - The progressive prevalence of home health care has caused an increase in number
      of kinds and quantities of medical waste at home in Japan. This causes various
      problems in the process of managing. To resolve these problems, enactment of
      laws, clarification of the roles and duty of municipalities/medical
      organizations/patients etc., including allocation of cost burdens for disposal,
      and construction of the total (well organized) waste management system will be
      required.

PMID- 10901049
TI  - [A trial of pollutant release and transfer register in a university school of
      medicine].
AB  - At Hamamatsu University School of Medicine, the Pollutant Release and Transfer
      Register (PRTR) was tried. The following results were obtained. On solid chemical
      substances, the stored quantity was comparatively greater than the purchased or
      disposed quantity. However, on liquid substances, the purchased volume was
      similar to the disposed volume.

PMID- 10901050
TI  - [Measures for the disposal of non-regulated alternative medical wastes--cloned
      DNA of amplified DNA as waste materials].
AB  - Cloned DNA of amplified DNA, synthesized oligomer DNA and peptide nucleic acid is
      a candidate for hazardous medical waste material. The numerous identical base
      sequence of DNA has a risk associated with its handling in a laboratory and
      medical waste. To avoid the risk SD box, NaOCl, filtered chip of micropipette and
      a clean-bench are recommended for waste management.

PMID- 10901051
TI  - [Measures for the disposal of non-regulated alternative medical wastes--prion
      protein-polluted medical waste].
AB  - Transmissible spongiform encephalopathy (TSE), sometimes known as prion diseases,
      are fatal degenerative brain diseases. From epidemiological evidence and many
      investigations of data, the risk that TSE agents will be transmitted from TSE
      patients to other humans, is very low, but TSE agents comprise one of the very
      severe bio-medical hazards. Although government agencies, world organization and
      other institutions have distributed some guidances for safe working and
      prevention of infection, these guidances are not compulsory and no globally
      harmonized guidelines is present to date. Therefore, medical staff particularly
      in hospitals individually take countermeasures for safety against TSE agents by
      using these guidelines, and both the level and method differ in each hospital. In
      this chapter, transmission of TSE and related parts of guidelines from the
      Advisory Committee on Dangerous Pathogens and Spongiform Encephalopathy Advisory
      Committee in the United Kingdom recommending relatively strict standards are
      described.

PMID- 10901052
TI  - [Measures for the disposal of non-regulated alternative medical wastes--effects
      of disinfectants on activated sludges].
AB  - Effects on activated sludges of several disinfectants with strong and wide
      antimicrobial ability, were investigated using an oxygen up-take method. As a
      results, at the maximal non-reactive concentration of disinfectants,
      hexachlorophene has estimated value of 6 mg/l and shows the highest toxicity
      against activated sludges. At the lethal concentration of 50%, the toxicity of
      triclosan is the strongest disinfectant.

PMID- 10901053
TI  - [Measures for the disposal of non-regulated alternative medical wastes--safe
      handling of cytotoxic drugs].
AB  - It is easy to come into contact with cytotoxic drugs, by touching or inhaling
      small quantities of the drug-containing aerosols or dusts. Contact with cytotoxic
      drugs can cause immediate problems, such as dermatitis, dizziness, nausea, and
      headache. Studies suggest that repeated exposure to small amounts of the drugs
      many cause organ or chromosome damage, impaired fertility, and even cancer. The
      evidence is not conclusive, but an approach that will minimize the possible risks
      is needed.

PMID- 10901055
TI  - Catalogues and theories (greetings card).

PMID- 10901054
TI  - Epigenetic heredity. In praise of Paul Kammerer.

PMID- 10901056
TI  - Homologies, analogies, synapomorphies and homoplasies: problems and
      considerations.
AB  - The author discusses, on the evidence of some typical examples, some problems in
      the assessment of homologies which have surfaced by the integration of
      ultrastructural and genetic evidences in the assessment of the morphologic and
      evolutionary significance of structures. He thence considers problems of correct
      assessment of homologies as true apomorphic rather than homoplastic traits and
      which are often overlooked in the construction of cladistic matrixes. His
      conclusions are that a more comprehensive approach in morphological research
      should be stressed and that a strong effort is badly needed for the development
      of classical comparative anatomy versus the present trend towards ultra
      specialized studies; moreover, at the present stage of research, the available
      evidence is generally quite insufficient for the development of reliable matrixes
      of data, so that a more empirical and pragmatic approach is much safer.

PMID- 10901057
TI  - The Hox-gene research programme and the shortcomings of molecular
      preformationism.
AB  - The study of the so-called HOM/Hox genes has provided many important insights on
      the control, at the molecular level, of developmental processes in a variety of
      model systems such as the fly and the mouse. Yet, in the specialised literature
      on the subject abound the claims that such genes, and the products coded by them,
      are the true morphogens responsible for determining the actual form of a
      particular organism. According to this view, morphogenesis results from the
      expression of specific 'master control' genes and thus, organic form is somehow
      pre-established (i.e., preformed) as an assembly programme encoded within the
      genome. Or in other words, it is claimed that the complex spatio-temporal order
      that leads to the achievement and maintenance of organic form is implied in a two
      dimensional organisation of the genome. Moreover, some authors have claimed that
      the success of the Hox-gene research programme strongly suggests that
      morphological evolution is a direct result of evolution at the genetic level.
      Hereunder I discuss recent evidence that falsifies the basic preformationist
      tenets of molecular developmental biology. Thus suggesting that the problem of
      the origin of organic form is left untouched by the Hox-gene research programme
      and therefore, there is a need to reconsider alternative approaches, such as the
      structuralist morphogenetic outlook, that are better suited to eventually explain
      the origin of organic form.

PMID- 10901059
TI  - Fields, networks, creativity and evolution.
AB  - Organisms constitute wholes as a result of a network of organizing relations
      between the parts. In animals, this network has a morphological as well as a
      psychological aspect, and it regulates morphogenesis as well as behaviour. It is
      pointed out that closed networks of higher order, that have the characteristics
      of single organisms (communities of ants, termites and bees, cases of symbiosis,
      and perhaps even the Earth), could also possess that regulating aspect. In the
      case of humans, the network can be associated with creativity and the structure
      of knowledge. Individuation (as defined in Jung's psychology) refers to the
      assimilation of the network into consciousness. The theory developed in the
      present paper could give rise to a multi-disciplinary approach to the study of
      life.

PMID- 10901058
TI  - Chemical and mechanical waves on the cortex of fertilized egg cells: a
      bioexcitability effect.
AB  - We analyse a mathematical model in order to describe the propagation of chemical
      and mechanical waves through the cortex of fertilized egg cells. The model is
      described by a partial differential equation of the reaction-diffusion kind. This
      model was formulated by Oster and Odell and its mechanism concerns a condition of
      excitability of the egg perturbed by fertilization. During this excitability
      stage one observes the development of a calcium wave which produces contraction
      and expansion waves in the cytogel. In particular, we consider the behaviour of
      ascidian eggs after fertilization, emphasizing that the model utilized is
      suitable to describe the first cortical movements of such eggs. Moreover, we
      suppose a new "excitability" state of these eggs, after the first ooplasmic
      segregation. This excitability state is located in the vegetal pole. Finally, we
      study the mechanical effects caused by a perturbation, which is induced in such
      vegetal region by increasing the calcium concentration in the culture medium.

PMID- 10901060
TI  - The evolution of the millennium bug.
AB  - How could mankind, knowing the year 2000 would inevitably arrive, manoeuvre into
      worldwide technical problems because of a little computer bug? Two major
      parallels can be drawn to biological systems, and both are based on evolutionary
      principles. First, any new steps in development are founded on building blocks
      invented earlier. Basic building blocks are hardly changed anymore because
      further developments depend on their function. Second, imperfections of such
      building blocks are irrelevant as long as no corresponding selection pressure
      exists. If a time-coded computer bug occurs sufficiently early during
      technological development it can become part of innumerous hard-wired or soft
      coded programs and devices without ever attracting attention. However, the
      arrival of a certain data can instantly put a high selection pressure upon it.
      This behaviour can be understood as a direct consequence of the autonomous
      dynamics that the development of complex systems implicates.

PMID- 10901061
TI  - Small acidic peptides and peptidomimetic molecules: cell growth and
      differentiation.
AB  - Small phosphorylated chromatin peptides exert a homeostatic regulation on gene
      expression which causes a strong inhibition of RNA synthesis and growth of
      neoplastic and fast-growing cells and a remarkable activation of metabolic
      pathways slowed down in ageing. By biochemical and mass spectrometry analysis,
      some molecular models of these peptides have been designed and synthesised.
      Recent studies show that it is possible to find peptidomimetic structures, such
      as citric acid, able to reproduce the antiproliferative effect. The mechanism of
      action has been investigated and partially clarified.

PMID- 10901062
TI  - Alterations in the genome of wheat seedlings grown under drought stress and the
      effect of gibberellic acid on these alterations.
AB  - The changes in the amount of nuclear, chloroplast and mithocondrial nucleic acids
      of wheat (Triticum aestivum L.) seedlings in relation with drought stress and the
      effect of gibberellic acid (GA3) on these changes were investigated by
      spectrophotometric method. It was found that drought stress caused decrease in
      the amount of nucleic acids. In the seedlings to which GA3 was applied following
      drought stress, increase in the amount of nuclear nucleic acids (especially in
      the amount of labile DNA, which is the active portion) was determined. Similar
      results were observed in the amount of nucleic acids of mitochondria and
      chloroplasts. All these results show that drought stress caused quantitative
      changes in the genetic substrate of wheat seedling cells and GA3 application
      alleviated this effect by activating the synthesis of nucleic acids.

PMID- 10901063
TI  - Drug interactions and the cytochrome P-450 system.

PMID- 10901064
TI  - Lifestyle satisfaction of rural, South Dakota, family practice physicians.
AB  - South Dakota (SD) rural, family practice physicians were surveyed relative to
      their lifestyle satisfaction. Sixty-eight of 192 surveys were returned (45%),
      with 75% men and 22% women responding (3% no response). Forty-nine percent of
      respondents had attended the University of South Dakota School of medicine.
      Besides overall satisfaction, factor analysis grouped survey questions into four
      clusters: a) activities; b) community; c) income; and, d) time. As compared to
      other physicians, those physicians who were born in SD or had graduated from a SD
      high school, or had received their undergraduate education in either SD or a
      bordering state, reported significantly greater overall satisfaction as well as
      significantly greater satisfaction with both the community and availability of
      leisure activities. Interestingly, there was no significant difference in
      lifestyle satisfaction among physicians who attended medical school in either SD
      or a bordering state, as compared to physicians who attended medical school
      elsewhere. It does appear that the degree of "connectedness" to SD positively
      impacts the lifestyle satisfaction of SD, rural, family practice physicians.

PMID- 10901065
TI  - [Time to re-establish special health care?].

PMID- 10901066
TI  - [Malaria--globally and locally].

PMID- 10901067
TI  - [How do we talk about smoking to smokers?].

PMID- 10901069
TI  - [Why do health personnel neglect to talk about passive smoking with parents of
      small children?].
AB  - BACKGROUND: Health personnel make only moderate efforts at motivating parents to
      establish a smoke-free indoor environment for babies and infants. It is only when
      children show symptoms of exposure to tobacco smoke that they routinely raise the
      question of passive smoking during consultations with the parents. We wanted to
      find out why so many neglect to raise the matter when there is still time to
      prevent injury to the child. MATERIAL AND METHODS: A pre-categorised
      questionnaire on possible obstacles to involvement in the matter was mailed to a
      representative sample of 1050 GPs, the senior midwives at Norway's 77 maternity
      departments, 492 senior public health nurses, and personnel at 1024 mother-and
      child clinics. The response rate varied from 71% (GPs) to 82% (senior midwives).
      RESULTS: Public health nurses, midwives and doctors at the clinics regard it as
      part of their work to talk to parents about the possible effects of passive
      smoking on their children's health. The obstacles are a feeling of embarrassment
      at raising the matter, and not knowing how to talk to the parents about the
      problem. Even so, a clear majority experience a positive response from smoking
      parents when they discuss how to prevent the children from inhaling tobacco
      smoke. Among the GPs the main reason for not raising the matter is lack of time,
      followed by embarrassment at taking it up and lack of knowledge about the health
      risks. INTERPRETATION: Health personnel seem to need training in conversation
      techniques in this connection.

PMID- 10901068
TI  - [Do health personnel talk about passive smoking with parents of small children?].
AB  - INTRODUCTION: Almost seven out of ten parents who smoke state that they have
      never received information on passive smoking from health personnel when they
      bring their children in for routine medical examination. We examined what GPs,
      doctors and nurses at mother-and-child clinics and midwives reported. MATERIAL
      AND METHODS: A self-administered questionnaire focusing on practice as regards
      the matter of passive smoking and children was mailed to a representative sample
      of 1050 GPs, the senior midwives at Norway's 77 maternity departments, 492 senior
      public health nurses, and health personnel at 1024 mother-and-child clinics. The
      response rate varied from 71% (GPs) to 82% (senior midwives). RESULTS: 70% of the
      personnel at mother-and-child clinics less often than "always" ask about exposure
      to passive smoking. 60% of the senior midwives report that the department's
      personnel less than "to a large extent" allocate time to talk with parents about
      passive smoking. 40% of the GPs and 50% of the paediatricians say that they
      "never" bring up the matter of passive smoking when they examine small children
      and do not know whether members of the household smoke or not. The rest of the
      GPs bring up the matter in 46% of consultations and the rest of the
      paediatricians in 63% of consultations. When the child has symptoms that can be
      associated with passive smoking, the GPs discuss the parents' smoking habits in
      88% of the consultations and paediatricians in 100% of consultations.
      INTERPRETATION: Only to a small extent do health personnel use their
      opportunities of motivating parents to change their smoking habits for the sake
      of the health of their children. Smoking is only brought up by professionals as a
      matter routine when the children develop symptoms of exposure to tobacco smoke.

PMID- 10901070
TI  - [Smoking cessation practice among Norwegian hospital physicians].
AB  - BACKGROUND: Limited data is available as to what extent Norwegian hospital
      doctors ask their patients about their smoking habits, and to what extent doctors
      offer their patients help in smoking cessation. MATERIAL AND METHODS: A random
      sample of 1,025 hospital doctors was mailed a questionnaire. After 14 days a
      reminder letter was sent to non-responders; 76% of the doctors responded.
      RESULTS: Altogether 98% of the doctors stated that they asked their patients with
      smoking-related disease about their smoking habits. In cases of non-smoking
      related disease, 73% of the doctors stated that they asked about the smoking
      habits of their patients (83% of female and 69% of male doctors). If doctors knew
      that a patient wanted to quit smoking, 25% of them stated that they often
      recommended nicotine replacement therapy. Less than 7% of the doctors regularly
      offered smoking cessation courses, handed out self-assistant material, or gave
      the patients other smoking cessation advice. INTERPRETATION: The study indicates
      that doctors often ask their patients about their smoking habits, but there is
      clear potential for improvement as to the smoking cessation advice.

PMID- 10901071
TI  - [Prevalence of smoking among high school teachers and students in Norway].
AB  - The Ministry of Health and Social Affairs has defined "smoke-free schools" and
      "role models" as priority objectives in a document describing the national
      strategy to prevent the harmful effects of tobacco. We have investigated smoking
      policies in upper secondary schools, and to what extent policies support these
      objectives. Heads of Schools or Counsellors at all 487 upper secondary schools in
      Norway were contacted by telephone. Up to five calls were placed to reach the
      right person. A total of 432 interviews were conducted (90% response) in the
      course of December 1998. 85% of upper secondary schools permit the teachers and
      90% permit the students to smoke in the school area. At 35% of the schools
      students and teachers smoke together on a daily basis. There are geographical
      differences in levels of restriction. 20% of the schools have prepared a plan of
      action against use of tobacco. Compared with schools without such a plan, smoking
      is less frequent among both teachers and students, and tobacco prevention
      activities are given higher priority. We conclude that public authorities should
      introduce a set of universal rules for smoking among students and teachers in the
      upper secondary school.

PMID- 10901072
TI  - [Prevalence of smoking among high school students and teachers in Hamar 1999].
AB  - BACKGROUND: The prevalence of tobacco smoking among adolescents in Norway is
      about 36% for men and 27-42% for women. We explored the situation among high
      school pupils in a small Norwegian town. MATERIAL AND METHODS: A questionnaire
      was distributed in the classroom of 62 classes. The classes comprised 79% of all
      high school pupils in the town. The pupils were not given the opportunity to
      communicate while they completed the questionnaires. Anonymity was guaranteed.
      RESULTS: 1,001 pupils (99.9%) completed the questionnaires, 1,000 (99.9%)
      answered all questions about smoking. 44% of the women and 36% of the men smoked.
      Among smokers, women significantly more often smoked 1-5 cigarettes per day,
      while men significantly more often smoked > 15 cigarettes per day. The prevalence
      of smoking was approximately 40% in the age groups 16-17 years, 18-19 years, and
      20-21 years. INTERPRETATION: Most adolescents who start smoking, start before
      entering high school. Although women more often tend to smoke, they smoke less
      than men. The prevalence of smoking among adolescents in Norway is still high.

PMID- 10901073
TI  - [Diagnosis of depleted iron stores--do not use s-iron].
AB  - BACKGROUND: Analysis of s-ferritin is recommended for the diagnosis of depleted
      iron stores, but other parameters are still in use. The objective of this study
      was to determine the accuracy for s-iron, s-transferrin, transferrin saturation,
      b-hemoglobin and erythrocyte-MCH in diagnosing depleted iron stores. MATERIAL AND
      METHODS: Data was collected from the Health Study of Nord-Trondelag, 1995-1997.
      Blood samples from 3029 women aged 20-45 were analysed for iron status. In
      absence of bone marrow aspirate, s-ferritin was used as the standard for iron
      deficiency. RESULTS: Highest diagnostic accuracy was found for s-transferrin. S
      iron did not contribute with significant independent information. INTERPRETATION:
      S-iron should not be used in the diagnosis of depleted iron stores.

PMID- 10901074
TI  - [Evaluation of the Norwegian Medical Association's campaign for improved
      contraception and fewer induced abortions].
AB  - BACKGROUND: Two thirds of the young women who want induced abortions have not
      used contraception, and it is likely that improved education in contraception
      will lead to a decline in induced abortions. The Norwegian Medical Association
      sees this as its responsibility, and in 1995 proposed a campaign to improve the
      quantity and quality of physicians' advice on contraceptive use. A booklet was
      produced and mailed with a poster to all general practitioners in May 1997.
      MATERIAL AND METHODS: Before the distribution of the information package a
      questionnaire on how contraception was taught was sent to a representative sample
      of 211 general practitioners. Six months later the same 211 received a similar
      questionnaire with a few questions added on the possible effect of the
      information package. RESULTS: 132 physicians responded the first time and 105 the
      second. Four out of five general practitioners have consultations where they
      advise on contraception at least weekly. 70% had attended courses on sexology or
      contraception. 80% found the booklet useful, and 12% had changed their routines
      as a consequence of the campaign. Routine examinations before prescription of
      contraceptives were more extensive than the booklet advises. There was no
      measurable difference in reported practice before and after the campaign, but by
      using the more than 20,000 potential annual consultations as the unit instead of
      the physicians, there were significant moves in the right direction.
      INTERPRETATION: Even if the evaluation cannot document improved contraception as
      a result of the campaign, the quality of the physicians' advice on contraception
      has improved.

PMID- 10901075
TI  - [Malaria in Norway--diagnosis, treatment and prevention].
AB  - The paper describes and discusses procedures and problems related to diagnostics,
      therapy and prophylaxis of malaria in Norway. A high degree of suspicion in
      physicians evaluating febrile travellers is of the utmost importance. The
      clinical symptoms and findings are initially rather unspecific, with fever and
      fever related symptoms. A definite diagnosis is made by the demonstration of
      malaria parasites in thin and thick blood smears, which is best performed by an
      infectious disease physician. Before treatment is started, it is important to
      determine whether the patient is infected with Plasmodium falciparum or with one
      of the more benign malaria species. If this is difficult microscopically, a test
      that detects P. falciparum antigen in blood may be useful in some cases. The
      therapy of benign malaria is still chloroquine plus primaquine; most patients
      with malaria falciparum can be routinely treated with mefloquine. Cases of
      complicated falciparum malaria, usually due to delayed diagnosis and start of
      treatment, require extensive and sophisticated treatment, usually including
      parenteral treatment with quinine. Prophylaxis consists of prevention of mosquito
      bites and chemoprophylaxis; the importance of avoiding bites should never be
      underestimated. A more widespread use of mefloquine among travellers to Africa is
      the most important change in chemoprophylaxis in recent years. Finally the
      article discusses possible improvements in diagnostic procedure, therapy and
      chemoprophylaxis.

PMID- 10901076
TI  - [Malaria imported to Norway 1989-98].
AB  - BACKGROUND: Increasing numbers of imported cases of malaria have been reported
      from several European countries. MATERIAL AND METHODS: By analysing data from the
      Norwegian Surveillance System for Communicable Diseases (MSIS) from 1989 to 1998,
      the incidence of imported malaria and the most important risk groups for
      acquiring the disease in endemic areas are assessed. RESULTS: In the ten-year
      period a total of 744 cases of malaria imported into Norway were reported. An
      increase in incidence has been observed during the period. Since 1992 Plasmodium
      falciparum has been the most common reported parasite. 58% of the cases were
      among people of non-Norwegian origin, and 41% among people of Norwegian origin.
      Immigrants from Pakistan, India and Sri Lanka constitute 26% of all imported
      cases. During the five year period from 1994 to 1998, 60% of patients of non
      Norwegian origin, and 19% of patients of Norwegian origin took no
      chemoprophylaxis prior to their illness. From 1994 to 1998, 23% of the patients
      developed malaria despite taking recommended chemoprophylaxis. The majority of
      these patients used chloroquine and proguanil and developed falciparum malaria
      after visiting sub-Saharan Africa. INTERPRETATION: Increased emphasis should be
      put on avoiding exposure to mosquitoes while in endemic areas. Mefloquine should
      be recommended as prophylaxis to the majority of travellers visiting regions with
      chloroquine-resistant malaria.

PMID- 10901077
TI  - [Falciparum malaria in Oslo and Akerhus].
AB  - BACKGROUND: Imported falciparum malaria in an increasingly frequent health
      problem in many areas in which it is not endemic. Complications are commonly
      seen, and reported case-fatality rates may exceed 3%. MATERIAL AND METHODS: The
      study is a medical chart-based retrospective study of all cases of falciparum
      malaria diagnosed in Oslo and Akershus counties, south-eastern Norway, 1988-1997.
      RESULTS: We identified 232 diagnosed cases; of these, records were available for
      222 cases (95%). The incidence rate almost quadrupled during the study period.
      The two largest groups were immigrants visiting their country of origin (35%) and
      Norwegian tourists (29%). 95% of the cases were infected in Sub-Saharan Africa.
      There were no fatal cases, and only eight cases (3.6%) developed complicated
      falciparum malaria. In a statistical analysis, the following factors were found
      to be significantly associated with complicated disease: higher age,
      noncompliance to recommended chemoprophylaxis in assumed non-immune subjects,
      prolonged doctor's delay and prolonged diagnostic delay. INTERPRETATION: The
      study suggests that complications in imported falciparum malaria may largely be
      prevented by a high rate of chemoprophylaxis compliance in non-immune travellers
      and a high awareness of this possibility among physicians evaluating febrile
      travellers from endemic areas.

PMID- 10901078
TI  - [WHO's malaria program Roll Back Malaria].
AB  - Malaria is one of the main health problems in the world with 300-500 millions
      cases yearly and about one million deaths, mainly children in Sub-Saharan Africa.
      In the 1990s the malaria problem in Africa has increased, although we have
      methods to control the disease. In 1998 the new secretary general of WHO, Gro
      Harlem Brundtland, established the Roll Back Malaria programme, with the aim to
      markedly reduce malaria morbidity and mortality. Governments in malaria-affected
      countries have to take the lead in Roll Back Malaria. Their health systems must
      be improved and malaria control integrated into the general health system, and
      the methods available for prevention and treatment have to be intensified and
      improved. At the same time, Roll Back Malaria will encourage and promote malaria
      research which hopefully will result in new medicines, vaccines and other tools
      which will improve the chances of reducing malaria-related deaths and suffering.
      Roll Back Malaria is a cabinet project within the WHO, and the organisation has a
      key role as manager, co-ordinator and monitor of the project. However, it depends
      for resources on international support and commitment from other UN bodies, the
      World Bank, governments in the western world, pharmaceutical industry,
      philanthropists and other sources. At present an optimistic view prevails, and
      the preliminary aim, to halve the malaria mortality by the year 2010, seems
      realistic even with the control methods of today. However, if research efforts
      result in new and better tools to combat the disease, the task will definitely be
      easier.

PMID- 10901079
TI  - [Malaria vaccines--which vaccines to whom?].
AB  - More than a third of the world's population is at risk of contracting malaria. It
      is estimated that 200 people, primarily children in Africa, die of malaria every
      hour of every day all year round. Malaria is one of the main obstacles to socio
      economic development in Africa. Vaccines against malaria are considered to be the
      control tool most in need of development. Fundamentally there are three types of
      malaria vaccines: vaccines against the invading sporozoite or the parasite's
      development in the liver cells, vaccines directed against the parasite's invasion
      of and development in the red blood cells; vaccines directed against the
      fertilisation process in the mosquito. Each malaria vaccine has its own area of
      application. In spite of promising results in animals it has been difficult to
      reproduce the results in clinical trials in humans. Recently, however, an
      experimental vaccine containing a sporozoite protein coupled to a hepatitis B
      surface molecule with a new adjuvant has been tested in Gambia. The results of
      these tests are promising, but it is unlikely that the vaccine will be of use in
      endemic areas. Increased focus on one of the world's biggest health problems has
      to a certain extent promoted the funding of development work on malaria vaccines.
      Despite minimal interest from the pharmaceutical industry, a number of
      experimental vaccines for clinical phase I trials are on their way. However, it
      will take a huge increase in public financial resources to secure effective and
      safe malaria vaccines for those most in need of them: people in developing
      countries and particularly in Sub-Saharan Africa.

PMID- 10901080
TI  - [Cancer risks using snuff].

PMID- 10901081
TI  - [Experiences with a smoking cessation project].

PMID- 10901082
TI  - [Ultrasonography early in the pregnancy].

PMID- 10901083
TI  - [The base of knowledge in psychiatry].

PMID- 10901084
TI  - [The family practice system--what went wrong?].

PMID- 10901086
TI  - Isoprostanes quickly normalize after quitting cigarette smoking in healthy
      adults.
AB  - BACKGROUND: Isoprostanes and in particular 8-epi-PGF2 alpha have been claimed as
      a useful measure for invivo oxidation injury. While smokers show elevated 8-epi
      PGF2 alpha the behaviour during quitting smoking is unknown. METHODS AND RESULTS:
      We determined 8-epi-PGF2 alpha in 7 healthy adults ready to quit smoking in
      plasma, serum and urine by means of an enzyme immunoassay after extraction and
      purification before quitting smoking and during a follow-up period of 4 weeks.
      After quitting smoking, 8-epi-PGF2 alpha shows a rapid decline within a few days
      almost completely normalizing within 4 weeks. CONCLUSION: The cigarette-smoking
      associated invivo oxidation injury almost completely disappears within 4 weeks of
      quitting smoking.

PMID- 10901085
TI  - Nitric oxide inhibits the basic fibroblast growth factor-stimulated migration of
      bovine vascular smooth muscle cells in vitro.
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of nitric oxide
      (NO) on basic fibroblast growth factor (bFGF)-stimulated migration of bovine VSMC
      in vitro. METHODS: For the migration assay 50,000 cells from passages 4 to 8 were
      put into a migration chamber and stimulated with 10 ng bFGF/ml (control group).
      For another experiment, the NO donator sodium nitroprusside (SNP) (10(-6), 10(
      8), 10(-10) M), the second messenger of NO 8-bromo-cGMP (10(-6), 10(-8), 10(-10)
      M) and 100 U of superoxide dismutase (SOD) were added. Migration of cells was
      quantified after fixing and staining of the cells by means of light microscopy.
      RESULTS: Cell migration was significantly inhibited by SNP in a dose dependent
      manner (p < 0.01 with t-test). This effect was mirrored by 8-bromo-cGMP and not
      significantly inhibited by SOD, confirming this to be an NO mediated effect and
      excluding side-effects of superoxide-derived oxidation products. CONCLUSION:
      Nitric oxide inhibits the basic fibroblast growth factor stimulated migration of
      bovine vascular smooth muscle cells in vitro.

PMID- 10901087
TI  - Alterations in capillary permeability in the lower limb of patients with chronic
      critical limb ischaemia and oedema.
AB  - BACKGROUND: Oedema formation in lower limbs of patients with chronic critical
      limb ischaemia (CLI) is a common clinical feature. The rate of fluid filtration
      through the capillary wall depends on the capillary permeability, i.e. capillary
      filtration coefficient (CFC). In order to elucidate the pathogenesis of this
      ischaemic oedema, CFC was measured in the limbs with CLI and oedema and was
      compared with CFC measurements both in the contralateral sides and in the lower
      limbs of a control group. PATIENTS AND METHODS: Eleven women and 4 men, with a
      mean age of 75 +/- 8.8 years, with unilateral CLI and leg and foot oedema were
      included. Leg and foot volume was measured with water displacement volumetry
      (WDV). CFC was measured in both limbs by strain-gauge plethysmography using a
      double-stranded mercury in silicone strain gauge around the middle portion of the
      foot. As a control group, 8 patients, 5 women and 3 men, with a mean age of 77 +/
      7.6 years with a proximal femur fracture were included and the CFC in this group
      was measured in the foot of the non-fractured limb. RESULTS: Mean CFC in the
      limbs with CLI and oedema was 0.0036 +/- 0.001 ml/min.100 ml.mmHg, significantly
      greater than both the contralateral limbs (0.0019 +/- 0.0003 ml/min.100 ml.mmHg,
      p < 0.01) and mean CFC in the control limbs (0.0017 +/- 0.0002 ml/min.100
      ml.mmHg, p < 0.003). There was a mean volume difference of 13 +/- 9% between
      limbs with CLI and contralateral sides measured by WDV. There was no significant
      correlation between total leg-foot volume and CFC (p > 0.05). CONCLUSION: CFC in
      the ischaemic limb was twice as great as both the contralateral side and the
      limbs of the control group. It is therefore concluded that an increased CFC is
      probably one of the important factors in the development of this ischaemic
      oedema.

PMID- 10901088
TI  - Incidence of cutaneous vasoactivity in patients with anemia and pulmonary
      hypoxia.
AB  - BACKGROUND: In cutaneous laser Doppler flow (LDF)-recordings, various forms of
      flowmotion or vasoactivity can be observed. It is still a matter of dispute,
      whether flowmotion is a phenomenon of physiological or pathophysiological
      conditions. Therefore, we tested the hypothesis of increased vasoactivity being
      typical for patients with various degrees of acute and chronic anemia as well as
      with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We
      examined 12 healthy controls, 14 patients with COPD with a PO2 below 60 mmHg, 16
      patients with chronic and 7 patients with acute anemia with an Hb below 12 g/dl.
      We used a simple LDF-technique on the dorsum of the forefoot. The regularity of
      blood flow frequencies was determined by calculation of the coefficient of
      variation. RESULTS: Periods without vasoactivity (i.e. constant flow pattern)
      were 21% in normal controls, 7% in patients with COPD and 2% in patients with
      acute or chronic anemia. Mean frequencies in the four groups varied between 3.8
      and 4.8 cpm, with significant changes only in the group with acute blood loss.
      However, vasoactivity was significantly more regular in the COPD- and anemia
      groups as compared to normal controls, with coefficients of variation of 47.4%
      for controls, 31.8% for COPD- and 29.3% for chronic and 35.1% for acute anemia
      patients. CONCLUSIONS: The present paper shows that cutaneous vasoactivity is
      more regular in the three examined clinical entities of systemic tissue hypo
      oxygenation, i.e. chronic and acute anemia and severe COPD as compared to healthy
      control subjects. Therefore, we hypothesize that increased vasoactivity
      constitutes a regulatory defense mechanism in cases of reduced oxygenation, by
      improving microcirculatory blood flow distribution.

PMID- 10901089
TI  - Healing characteristics of small-calibre vascular prostheses coated with plasmin
      treated fibrin--an experimental study.
AB  - BACKGROUND: The autogenous vein represents the graft material of choice in crural
      and pedal bypass surgery. Because of the numerous problems concerning the graft
      harvesting and the quality of autogenous vein material an equally good allogenous
      graft is urgently needed. Up to the present times no such graft material has been
      able to achieve the success of vein grafts. METHODS: We investigated the knitted
      polyester prosthesis Terumo PF-V (Terumo Comp., Japan), diameter 5 mm with outer
      reinforce, which is characterized by a new coating of plasmin-treated fibrin.
      Grafts were implanted as bypass into the ligated carotid (n = 10) and femoral
      arteries (n = 10) of 10 dogs (beagles). As a control 5 mm-ePTFE-prostheses (Impra
      Carboflo) were implanted simultaneously on the contralateral side. RESULTS: After
      6 months, seven of 20 PF-V-grafts and 8 of 20 PTFE-grafts were patent. All
      prostheses presented with good macroscopic healing characteristics. In the patent
      grafts, angiography showed no substantial stenoses. The histological examination
      of the material was performed using light microscopy, transmission polarising
      microscopy, scanning electron microscopy, and transmission electron microscopy.
      Both types of prostheses showed the typical pattern of graft healing by migration
      of mesenchymal cells through the prosthesis, formation of capillaries, and
      growing of a neointima with endothelium-like cells. All failed bypass grafts
      presented with an occluding proliferation from the arterial wall into the
      anastomotic region. CONCLUSIONS: Using clinically or histologically evaluation,
      neither graft demonstrated superiority over the other. The results indicate that
      the coating plays only a minor role for graft healing if any. For proper graft
      function, the arterial wall proliferation at the anastomotic region, which is not
      dependent on the type of prosthesis, appears to be most important. The overall
      results concerning both types of prostheses were disappointing.

PMID- 10901090
TI  - The chronic venous compartment syndrome.
AB  - BACKGROUND: A chronic exertional compartment syndrome has only been observed in
      athletes and soldiers. In the vast majority, the disease affects the anterior
      compartment and the fibular muscle group, and only rarely the lateral and dorsal
      muscle compartments. Muscle tissue necrosis does not occur. In the course of
      venous diseases with a severe chronic venous stasis syndrome, a chronic venous
      compartment syndrome develops that differs considerably from the familiar
      functional syndrome. The predominant symptom is an uncurable cuff ulceration on
      the lower leg. PATIENTS AND METHODS: From 1993 to 1996 a total of 16 patients
      with a chronic fascial compression syndrome underwent surgery on 18 extremities.
      The crural fascia was resected and a mesh graft was applied. RESULTS: In the
      group of ten controls with healthy veins the average pressure in the deep
      compartment was 13.6 mmHg (range 9-17 mmHg) lying down and 29.9 mmHg (range 15-42
      mmHg) standing up. In 14 patients with chronic fascial compression syndrome, the
      average pressure was higher, measuring 21.1 mmHg (range 8-47 mmHg) lying down and
      62.5 mmHg (range 33-87) standing up. After surgery, the pressure dropped to 15.5
      mmHg (range 5-24 mmHg) lying down and 34.5 mmHg (range 10-58 mmHg) standing up,
      but did not fall as low as the average values recorded in the control group or in
      the patient's healthy leg. The results from the standing up position were
      statistically significant (p = 0.003). Computed tomography showed major changes
      in the muscles indicating muscle atrophy and fatty degeneration. The crural
      fascia seemed to be incorporated in the scars of the subcutaneous tissue in large
      areas. After crural fasciectomy and healing of the ulceration, the tissue
      structure of the muscles recovered. CONCLUSIONS: In chronic fascial compression
      syndrome, the trellis arrangement of the collagen fibres becomes disordered. This
      results in a loss of flexibility during muscle contraction. Every step causes an
      increase of intracompartmental pressure and microstructural injury. The
      consequence is resection of the crural fascia.

PMID- 10901091
TI  - Cardiovascular interventions during oncologic surgery: technical principles and
      mid-term survival.
AB  - BACKGROUND: While the veins are primarily affected by compressing or invasive
      tumors, the arteries usually undergo only a less pronounced stenosis, due to the
      higher internal pressure. However, some tumors infiltrate the arterial adventitia
      which should be resected or might be injured in cases where radical surgery is
      attempted. PATIENTS AND METHODS: We report some technical principles utilized in
      various vascular localizations and mid-term survival observed in a group of 35
      patients in whom a vascular reconstruction was performed during the surgical
      treatment of a malignant tumor. The following vessels were involved: carotid
      artery (n = 5), superior vena cava (n = 9), aortic arch (n = 1), subclavian
      artery (n = 1), right atrium +/- inferior vena cava (n = 6), abdominal aorta (n =
      3) and finally iliac artery and/or vein (n = 10). The following surgical
      techniques were employed: extra-anatomic bypass (n = 3), in situ reconstruction
      (n = 23) using either prosthetic graft or saphenous vein interposition, patch
      angioplasty with autologous vein or xenopericardium and ligature of the involved
      artery or vein (n = 4). In 5 patients suffering from hypernephroma with a tumor
      thrombus, cardiopulmonary bypass was used to allow radical intracardiac excision.
      RESULTS: There was no intraoperative mortality despite the fact that a majority
      of these vascular procedures was performed after incidental and unexpected
      finding during surgery. Two patients died before hospital discharge (one from
      pneumonia, the second one from sepsis). Mid-term survival was satisfactory with
      45% of the patients still alive after a mean follow-up of 4.5 years--all tumor
      types confounded. CONCLUSIONS: This series demonstrates that an aggressive
      approach might be justified in appropriate patients who otherwise might not be
      considered as operative candidates.

PMID- 10901092
TI  - Renal artery stenting following acute aortic dissection: implantation and follow
      up.
AB  - Two patients with renal artery involvement in type B dissection of the aorta were
      treated by percutaneous stent implantation. Both of them were hypertensive and
      showed increasing serum creatinine levels. After stent implantation in the renal
      arteries blood pressure and renal function improved, and the renal arteries were
      patent in duplex ultrasound 15 and 30 months after treatment respectively.

PMID- 10901093
TI  - [Angina abdominalis: duplex ultrasound diagnosis and percutaneous
      revascularization].
AB  - Intestinal ischemia is still a challenge for clinicians and requires a close
      interdisciplinary cooperation between internist, surgeon and radiologist. In the
      last years the diagnosis and therapy, classically invasive and surgical, was
      supplemented by duplex ultrasound and percutaneous techniques like angioplasty
      and stenting. A 56 year-old man from Greece presented with epigastric pain, which
      was intensified by food ingestion. These symptoms were caused by a stenosis of
      the superior mesenteric artery, which was diagnosed by duplex sonography and
      angiography. No blood flow was detected in the inferior mesenteric and the celiac
      artery. Occlusion of one internal carotid artery made the patient a poor
      candidate for surgery. Therefore an interventional approach was chosen. A good
      result was achieved by angioplasty and stent implantation. On the day after the
      intervention oral food intake was possible without any pain. 18 months after the
      intervention the patient was free of abdominal symptoms. Therapy of mesenteric
      ischemia by percutaneous angioplasty and stenting is published only in case
      reports and small series. Therefore the indication is mainly restricted to
      patients with a high risk for a surgical intervention.

PMID- 10901094
TI  - Endovascular stentgraft infection--a life-threatening complication.
AB  - The implantation of covered stents or stentgrafts has increased greatly in the
      last few years for the endovascular reconstruction of arterial aneurysms. We
      report of three patients experiencing severe septic complications after
      stentgraft implantation. Endovascular stentgraft infection is a serious
      complication with high morbidity and mortality. General antibiotic prophylaxis
      seems to be indicated when implanting stentgrafts.

PMID- 10901095
TI  - A tennis player with hand claudication.
AB  - The case of a professional tennis player presenting exercise-induced hand pain
      with late appearance of digital blanching is reported. A bilateral hypothenar
      hammer syndrome and stenosis of the common palmar digital arteries close to the
      head of the metacarpals where the racket handle exerts its maximal force was
      observed with arteriography. As the patient decided to stop tennis practice, the
      condition improved without any medication. Six months after stopping tennis he
      was symptom free. Three conclusions can be drawn from this case report: 1)
      arteries of both hands can be injured by intense tennis practice, 2) pain in the
      dominant hand during tennis practice can be due to arterial insufficiency even in
      the absence of digital blanching which is a sign of severity, 3) hypothenar
      hammer syndrome is the main cause but stenosis of the common palmar digital
      arteries can possibly contribute to the ischemic phenomenon. Early recognition is
      important to avoid ineffective treatment and permanent symptoms. Therefore, we
      recommend an arterial examination in tennis players suffering from exercise
      induced hand pain even in the absence of digital blanching which can be only a
      late manifestation.

PMID- 10901097
TI  - Bacterial population of chronic crural ulcers.

PMID- 10901096
TI  - [Mandatory patient education for Doppler/duplex ultrasound imaging of the
      extracranial cerebral arteries?].

PMID- 10901098
TI  - Dengue/dengue haemorrhagic fever.

PMID- 10901099
TI  - Performance of acute flaccid paralysis (AFP) surveillance and incidence of
      poliomyelitis, 1999-2000 (data received in WHO Headquarters as of 1 June 2000).

PMID- 10901100
TI  - Magnetic resonance osteodensitometry in human heel bones: correlation with
      quantitative computed tomography using different measuring parameters.
AB  - RATIONALE AND OBJECTIVES: Density of trabecular bone structures in human heel
      bones was assessed by 3D magnetic resonance (MR) gradient echo imaging (GEI) with
      multiple echoes. Different spatial resolutions were applied to investigate the
      influence of the pixel size on signal characteristics in GEI and to find suitable
      measuring parameters for a maximum correlation between GEI and bone mineral
      density obtained by quantitative computed tomography (QCT). METHODS: Thirty-five
      patients aged 31 to 65 years with suspected osteoporosis underwent MR and QCT
      examinations of the heel bones. The MR protocol included 3D GEI with three echo
      times (TE1 = 9.3, TE2 = 27.9, and TE3 = 46.5 ms) and isotropic pixel sizes of
      (0.6 mm)3, (1.2 mm)3, and (2.4 mm)3. Several subregions in the heel bones were
      analyzed. For determination of signal reduction with increasing TE, signal
      intensity ratios were calculated pixelwise from images with TE2/TE1 and TE3/TE1.
      RESULTS: All examinations showed that the T2*-related signal decrease was more
      pronounced for lower spatial resolution. In the dorsal part of the heel bones,
      the correlation between signal ratios in GEI and QCT-based bone mineral density
      values was between r = -0.86 for a spatial resolution of (0.6 mm)3 and r = -0.73
      for (2.4 mm)3. Areas with low trabecular density in the ventral part of the heel
      bones showed clearly lower correlation coefficients (-0.65 < r < -0.67).
      CONCLUSIONS: Spatial resolution in 3D GEI clearly influences the T2*-related
      signal characteristics. Despite measuring different physical properties of spongy
      bone by GEI and QCT, a relatively high correlation between GEI with small pixel
      sizes and QCT was obtained in the dorsal part of the heel bones, but not in the
      ventral part with partly thickened trabeculae and irregular distribution.
      However, standardized measuring protocols with preferably small pixel sizes (as
      low as [0.6 mm]3) should be applied, and correlation curves must be determined,
      dependent on the actual bone marrow site, before clinical routine MR
      osteodensitometry becomes possible.

PMID- 10901101
TI  - Contrast-reduced imaging of tissue concentration and arterial level (CRITICAL)
      for assessment of cerebral hemodynamics in acute stroke by magnetic resonance.
AB  - RATIONALE AND OBJECTIVES: To compare cerebral perfusion data obtained by using a
      low-dose, T1-weighted MRI technique with radionuclide (single positron emission
      computed tomography [SPECT]) brain imaging and to assess the reproducibility of
      parametric MRI data (cerebral blood flow [CBF], cerebral blood volume [CBV], and
      time to peak [TTP]) by applying a previously described nuclear medicine technique
      to derive quantitative perfusion data. METHODS: Single-slice brain and neck
      images were rapidly acquired during the passage of a small (1/10th of normal
      dose) bolus of contrast. Parametric images were constructed from the MR data by
      extracting the bolus transit curve for the brain and the peak arterial input
      curve from the carotid vessels in the neck. These were compared with SPECT
      perfusion imaging. Twenty-four patients with acute stroke were studied with both
      techniques; 13 underwent repeated scanning to assess data reproducibility.
      RESULTS: Relative CBF data were comparable to SPECT data (r = 0.584, P = 0.01).
      Results were reproducible for relative CBF, CBV, and TTP. The arterial input
      function was significantly different on the second injection with an average
      difference of 73.5, suggesting that the signal-concentration relationship had
      lost linearity with increased contrast load. Absolute quantitative MRI data
      produced values in the expected range (CBF = 42.6 mL x 100 g(-1) x min(-1)).
      CONCLUSIONS: This technique allows estimation of CBF in the setting of acute
      stroke with quantitative values in the expected range. Repeated measurements in
      the same patients showed that this technique provides a reproducible measure of
      relative CBF, CBV, and TTP.

PMID- 10901103
TI  - Percutaneous delivery of a heparin-impregnated collagen stent-graft in a porcine
      model of atherosclerotic disease.
AB  - RATIONALE AND OBJECTIVES: To develop collagen stent-grafts impregnated with
      heparin to improve the biocompatibility of endovascular stents and to design a
      percutaneous delivery system for graft deployment in a swine model. METHODS:
      Heparin-impregnated collagen stent-grafts were deployed, and follow-up angiograms
      were obtained every 15 minutes for 90 minutes to assess acute thromboses and
      again at 2 and 4 weeks afterward to assess patency. If stenosis or occlusion was
      detected at the 2-week evaluation, guidewire passage across the lesion was
      attempted and angioplasty was performed. If stenosis or occlusion was present at
      the 4-week evaluation, only guidewire passage was attempted; thereafter, the
      animals were killed and the stent-grafts were harvested and reviewed by a
      vascular pathologist. RESULTS: Group A represents a feasibility study to optimize
      the deployment method applied in groups B and C. Fifteen of 17 stent-grafts were
      successfully deployed using this method. In group B, 89% of grafts were
      successfully deployed; 12% were patent at 2 weeks and none at 4 weeks. In group
      C, a 10-minute inflation time was added to the deployment procedure; 88% of
      grafts were successfully deployed and 28% were patent at 2 weeks and 14% at 4
      weeks. Extensive luminal thrombosis and myointimal hyperplasia were present in
      every case. CONCLUSIONS: A method was developed for percutaneous implantation of
      collagen stent-grafts into peripheral vessels. The heparin-impregnated grafts did
      not prevent vessel restenosis. Modification of the graft-processing technique may
      improve patency.

PMID- 10901102
TI  - Magnetic resonance imaging in patients with central nervous system pathology: a
      comparison of OptiMARK (Gd-DTPA-BMEA) and Magnevist (Gd-DTPA).
AB  - RATIONALE AND OBJECTIVES: The objective of the two pivotal phase 3 studies was to
      evaluate the safety and efficacy of OptiMARK (Gd-DTPA-bis(methoxyethylamide) [Gd
      DTPA-BMEA]) compared with Magnevist (Gd-DTPA) in magnetic resonance imaging of
      the central nervous system. METHODS: Two multicenter, randomized, double-blind,
      parallel group studies were conducted in 395 patients with known or suspected
      central nervous system pathology. Subjects were randomized to receive a single
      0.1 mmol/kg intravenous injection of either Gd-DTPA-BMEA or Gd-DTPA. The safety
      of Gd-DTPA-BMEA and Gd-DTPA was monitored for up to 72 hours after study drug
      administration. Precontrast and postcontrast administration magnetic resonance
      scans were acquired using identical imaging planes and techniques. RESULTS: No
      deaths or unexpected adverse events were reported in either group. A comparison
      of adverse events by intensity and relation demonstrated no statistically
      significant differences between the two groups. Gd-DTPA-BMEA and Gd-DTPA were
      equivalent with respect to confidence in diagnosis, conspicuity, and border
      delineation. CONCLUSIONS: Gd-DTPA-BMEA and Gd-DTPA demonstrated comparable
      efficacy profiles, and the safety profiles were considered similar.

PMID- 10901104
TI  - Preoperative contrast-enhanced MRI of the parathyroid glands in
      hyperparathyroidism.
AB  - RATIONALE AND OBJECTIVES: To evaluate the sensitivity of contrast-enhanced MRI in
      the preoperative detection of abnormal parathyroid glands in patients with
      clinical evidence of hyperparathyroidism. METHODS: Twenty-eight patients with
      biochemical evidence of hyperparathyroidism underwent contrast-enhanced
      preoperative MRI of the parathyroid glands. Two blinded readers assessed the MR
      images by consensus, and MR results were subsequently correlated with those from
      surgery (location, diameter, weight) and histopathology. RESULTS: MRI depicted 32
      of 39 surgically proved abnormal parathyroid glands (sensitivity 82%; 95%
      confidence interval, 66%-92%), and 1 of 114 (0.9%) was incorrectly considered
      abnormal. All ectopic glands were correctly identified (2 mediastinal, 1
      submandibular). Sensitivity was superior for adenomas but less for hyperplasia
      (adenomas 87%; 95% confidence interval, 67%-97%; hyperplasia 75%; 95% confidence
      interval, 47%-92%). Among all lesions, atypical signal characteristics on MRI
      were observed in 34% of lesions (9% hyperintense signals on T2- and T1-weighted
      images; 25% isointense signals on T2- and T1-weighted images), with improved
      lesion detection after contrast administration in 17% of lesions. CONCLUSIONS:
      MRI of the parathyroid glands presented a sensitive imaging modality, thus
      demonstrating its high potential to preoperatively detect abnormal glands.
      Moreover, in a minor proportion of patients with atypical parathyroid lesion
      characteristics, contrast administration may increase lesion detectability.

PMID- 10901105
TI  - Hydro-MRI in Crohn's disease: appraisal of disease activity.
AB  - RATIONALE AND OBJECTIVES: To appraise the value of hydro-MRI in the assessment of
      activity in Crohn's disease. METHODS: After bowel opacification with 1000 mL of
      an orally administered 2.5% mannitol solution was achieved, axial and coronal
      breath-hold sequences (T2-weighted half-Fourier acquisition single-shot turbo
      spin-echo sequences with or without fat saturation, dynamic T1-weighted fast low
      angle shot sequences, and contrast-enhanced T1-weighted fast low-angle shot with
      fat saturation sequences) were acquired in 82 patients with proved Crohn's
      disease at 1.0 T. Enhancement of the bowel wall was correlated with other MRI
      findings, with the Crohn's disease activity index (CDAI), and with levels of C
      reactive protein (CRP). RESULTS: In Crohn's disease, contrast enhancement of the
      affected bowel wall was markedly increased in comparison with the normal bowel
      wall (+80% +/- 22% versus +43% +/- 12%; P = 3 x 10(-15)). Positive correlations
      could be established between the increase in bowel wall enhancement and many
      other MRI findings. Between the increase in bowel wall enhancement and the CDAI,
      only a poor correlation was found (r = 0.25, P = 0.02). There was no statistical
      correlation between the increase in bowel wall enhancement and CRP. CONCLUSIONS:
      Hydro-MRI seems to be superior to the CDAI and CRP for the registration of
      Crohn's disease activity. In particular, differentiation between an active and an
      inactive (scarred) stenosis, which is crucial for the choice of therapeutic
      procedures, seems to be more reliable by the interpretation of several
      morphological and functional parameters on hydro-MRI than by the use of CDAI and
      CRP.

PMID- 10901106
TI  - A comparative study on validation of a novel cooled-wet electrode for
      radiofrequency liver ablation.
AB  - RATIONALE AND OBJECTIVES: A cooled-wet electrode has been developed for
      radiofrequency ablation (RFA) that allows simultaneous internal-cooling perfusion
      ("cooled") and interstitial hypertonic saline infusion ("wet"). The present
      comparative study was conducted to validate this new device for the increased
      coagulation volume in RFA. METHODS: Under low-power (50 W, groups A through F)
      and high-power (90 W, groups A' through F') control modes, 240 RFA lesions were
      created on excised beef liver to compare the cooled-wet electrode with other
      monopolar electrodes. The experimental regimens were as follows: groups A and A',
      conventional RF electrode; groups B and B', cooled electrode; groups C and C',
      wet electrode; groups D and D', cooled-wet electrode; groups E and E', cooled-wet
      electrode but suspended wet function; and groups F and F', cooled-wet electrode
      but suspended cooled function. The ablation efficacy was evaluated by comparing
      the lesion sizes as well as parameters of impedance, power output, current, and
      tip temperature. RESULTS: With lower impedance and tip temperature but higher
      power output, the lesion size in groups D (4.90 +/- 0.60 cm) and D' (6.6 +./-
      0.99 cm) was significantly larger than that in other groups. CONCLUSIONS: The use
      of the cooled-wet electrode could efficiently increase the lesion size for liver
      ablation.

PMID- 10901107
TI  - A minimally invasive method for creating coronary stenosis in a swine model for
      MRI and SPECT imaging.
AB  - RATIONALE AND OBJECTIVES: To develop a less-invasive method for creating coronary
      stenosis in an animal model for the study of myocardial perfusion defects by
      using magnetic resonance imaging (MRI) and single-photon-emission computed
      tomography (SPECT). METHODS: Eleven farm pigs were instrumented with an MR
      compatible coronary flow-reduction fitting in the left anterior descending
      coronary artery (LAD). These fittings were turned from a nylon rod, tapered from
      a maximum outer diameter of 3 mm, and drilled to a specified inner diameter
      (depending on the degree of coronary stenosis desired). The flow-reducing
      fittings were delivered over a coronary guidewire and advanced to a wedge
      position in the proximal LAD with an angioplasty catheter via a carotid artery
      approach. Perfusion determined by contrast-enhanced MRI at peak dipyridamole
      stress was compared with that obtained by 99mTc sestamibi SPECT. Radiolabeled
      microspheres were injected at rest, after stenosis implantation, and at peak
      pharmacological stress to establish the severity of the coronary lesion. RESULTS:
      Coronary stenosis was successfully created in seven animals. Mild coronary
      stenoses (<60%) were created in four animals. Significant coronary stenoses (80%
      90%) were created in three animals. Thrombosis of the coronary flow-reducing
      fittings was observed in four animals, leading to sudden death in three animals
      and myocardial infarction in one animal. CONCLUSIONS: This method of angioplasty
      guided, LAD coronary stenosis creation in a swine model presents a less-invasive
      alternative to open-chest techniques such as hydraulic occluders and ameroid
      constrictors.

PMID- 10901108
TI  - Environment, reproductive health and epidemiology.

PMID- 10901109
TI  - Male-mediated spontaneous abortion among spouses of stainless steel welders.
AB  - OBJECTIVES: Male-mediated spontaneous abortion has never been documented for
      humans. The welding of stainless steel is associated with the pulmonary
      absorption of hexavalent chromium, which has genotoxic effects on germ cells in
      rodents. Clinical and early subclinical spontaneous abortions were examined among
      spouses of stainless-steel welders. METHODS: A cohort of first-pregnancy planners
      was recruited from members of the union of metal workers and 3 other trade
      unions. The cohort was followed for 6 menstrual cycles from the cessation of
      contraceptive use. Altogether, 280 pregnancies were conceived, of which 35 were
      detected by human chorionic gonadotrophic hormone analysis and did not survive to
      a clinically recognized pregnancy. Information on exposure was collected
      prospectively in relation to the outcome and was available for all cycles
      resulting in a pregnancy. Information on pregnancy outcome was collected for all
      245 clinically recognized pregnancies. RESULTS: Increased risk of spontaneous
      abortion was found for pregnancies with exposure to paternal stainless-steel
      welding (adjusted relative risk 3.5, 95% confidence interval 1.3-9.1). The
      results were consistent in analyses of both biochemically and clinically
      recognized abortions. There was no increased risk for spontaneous abortion in
      pregnancies with paternal exposure to the welding of metals other than stainless
      steel. CONCLUSIONS: Male welding of stainless steel was associated with an
      increased risk of spontaneous abortion in spouses. A mutagenic effect of
      hexavalent chromium has been found previously in both somatic and germ cells, and
      the findings could be due to mutations in the male genome.

PMID- 10901110
TI  - Maternal occupation in agriculture and risk of limb defects in Washington State,
      1980-1993.
AB  - OBJECTIVES: This study examined the association between maternal occupational
      exposure to agricultural chemicals and the risk of limb defects among offspring.
      METHODS: A retrospective cohort study was conducted using Washington State birth
      records for the years 1980 through 1993. The exposed group, consisting of 4466
      births to mothers employed in agriculture, was compared with 2 reference groups:
      (i) 23,512 births in which neither parent worked in agriculture
      ("nonagricultural" group) and (ii) 5994 births in which only the father worked in
      agriculture ("paternal agriculture" group). The outcome of interest was limb
      defects [syndactyly, polydactyly, adactyly, and "other limb reductions" (as
      listed in the birth record)]. RESULTS: An elevated risk of limb defects was
      observed for the exposed group in comparison with both the nonagricultural and
      paternal agriculture groups, with ethnicity-adjusted prevalence ratios of 2.6
      [95% confidence interval (95% CI) 1.1-5.8] and 2.6 (95% CI 0.7-9.5),
      respectively. CONCLUSIONS: These results support the hypothesis that maternal
      occupational exposure to agricultural chemicals may increase the risk of giving
      birth to a child with limb defects.

PMID- 10901111
TI  - Time to pregnancy and infertility among women with a high intake of fish
      contaminated with persistent organochlorine compounds.
AB  - OBJECTIVES: The purpose of this study was to assess the effect of persistent
      organochlorine compounds through the dietary intake of fatty fish from the Baltic
      Sea on human fertility. METHODS: Information on time to pregnancy, subfertility,
      and infertility was collected retrospectively by self-administered questionnaires
      in 2 cohorts of fishermen's wives from the Swedish east (by the Baltic Sea) and
      west coasts. In addition to cohort affiliation, current fish consumption and
      growing up in a fishing village were used as proxies for exposure within the
      eastcoast cohort. RESULTS: A decreased success (ie, pregnancy) rate and a
      tendency towards increased subfertility was found for heavy smokers (> or =10
      cigarettes/day) in the eastcoast cohort as compared with the westcoast cohort
      [success rate ratio 0.66, 95% confidence interval (95% CI) 0.49-.89; subfertility
      odds ratio 1.64, 95% CI 0.91-2.91). However, internal analyses within the
      eastcoast cohort did not show that growing up in a fishing village or high
      current fish consumption decreased the success rate. Eastcoast cohort affiliation
      showed an increased risk for infertility (odds ratio 2.49, 95% CI 1.05-5.92).
      CONCLUSIONS: The present data give some support for a negative association
      between exposure to persistent organochlorine compounds and fertility among heavy
      smokers. However, when the proxy exposure measures are also considered, the
      findings are not consistent. Better individual exposure assessments should be
      used before more firm conclusions are drawn.

PMID- 10901112
TI  - Medical and psychometric examinations of conscripts born to mothers with a high
      intake of fish contaminated with persistent organochlorines.
AB  - OBJECTIVES: The present study aimed to investigate whether boys who had been pre-
      and postnatally exposed to persistent organochlorine compounds through the
      consumption of contaminated fatty fish from the Baltic Sea (on the east coast of
      Sweden) had medical or psychometric impairments in the compulsory conscript
      examination at 18 years of age. METHODS: Boys born in 1973 to 1975 to fishermen's
      wives and fishermen's sisters from the Swedish east coast were examined at 18
      years of age. For relevant comparisons a corresponding group from the Swedish
      west coast, where the fish are less contaminated, were used. In addition,
      comparisons were made with expected values based on conscript examination data
      for the general population in the same geographic areas. RESULTS: The boys in the
      2 cohorts did not, during the conscript testing, significantly differ in the
      results of the psychometric tests. On the other hand, the boys from the eastcoast
      cohort were somewhat shorter and had more visual and hearing impairments than the
      boys from the west coast. However, the eastcoast boys did not differ from the
      regional reference population with respect to visual and hearing ability.
      CONCLUSIONS: Although no individual exposure data were available, the present
      results do not support any harmful long-term impact of pre- and postnatal
      exposure to persistent organochlorine compounds from mothers' fish consumption on
      the psychometric functions of boys in their conscript examinations.

PMID- 10901113
TI  - Biological monitoring of N-methyl-2-pyrrolidone using 5-hydroxy-N-methyl-2
      pyrrolidone in plasma and urine as the biomarker.
AB  - OBJECTIVES: The aims were to study the toxicokinetics of 5-hydroxy-N-methyl-2
      pyrrolidone (5-HNMP) in blood and urine after exposure to N-methyl-2-pyrrolidone
      (NMP) and to study the suitability of 5-HNMP as a biomarker for assessing NMP
      exposure. METHODS: Six male volunteers were exposed for 8 hours to NMP
      concentrations of 0, 10, 25, and 50 mg/m3. Blood and urine were sampled before,
      during, and up to 40 hours after exposure. Aliquots of urine and plasma were
      purified, derivatized, and analyzed for 5-HNMP on a gas chromatograph/mass
      spectrometer in the electron impact mode. RESULTS: The mean plasma concentration
      [P-(5-HNMP)] after 8-hour NMP exposure to 10, 25, and 50 mg/m3 was 8.0, 19.6, and
      44.4 micromol/l, respectively. The mean urinary concentration [U-(5-HNMP)] for
      the 2 last hours of exposure was 17.7, 57.3, and 117.3 mmol/mol creatinine,
      respectively. The maximal P-(5-HNMP)and U-(5-HNMP) concentrations occurred 1 hour
      and 0-2 hours, respectively, after the exposure. The half-times of P-(5-HNMP) and
      U-(5-HNMP) were 6.3 and 7.3 hours, respectively. The 5-HNMP urinary
      concentrations were 58% of the calculated retained dose. There was a close
      correlation (r) between P-(5-HNMP) (r=0.98) and U-(5-HNMP) (r=0.97) with NMP
      exposure. CONCLUSIONS: 5-HNMP is an excellent biomarker for assessing exposure to
      NMP. Its plasma and urinary half-times (6-7 hours), the minimal risk for
      contamination during sampling in occupational settings, and the close correlation
      of P-(5-HNMP) and U-(5-HNMP) with NMP exposure makes 5-HNMP suitable for
      monitoring exposure to NMP. 5-HNMP in plasma is recommended.

PMID- 10901114
TI  - Psychological test performance during experimental challenge to toluene and n
      butyl acetate in cases of solvent-induced toxic encephalopathy.
AB  - OBJECTIVES: This study determined whether performance in neurobehavioral tests
      deteriorates during subjectively annoying chemical challenge below known
      neurotoxic thresholds among persons with toxic encephalopathy with subjective
      hypersensitivity to chemicals. METHODS: Subjects with symptoms and previous
      neuropsychological test results compatible with toxic encephalopathy (TE) of
      either type 2A (N=12) or 2B (N=12) and unexposed referents (N=12) were challenged
      in an exposure chamber. In a counterbalanced design, the subjects were exposed on
      2 occasions to increasing air concentrations of n-butyl acetate and toluene at
      levels well below the thresholds for neurotoxic effects. Attention and motor
      speed tests were given (i) in room air outside the chamber before the challenge,
      (ii) in room air inside the chamber before the exposure, (iii) at 12 ppm (44 or
      56 mg/m3), and (iv) at 48 ppm (at 180 or 228 mg/m3). RESULTS: For both substances
      the TE groups showed a slight increase (deterioration) in the simple reaction
      time task during chemical exposure, but not in the complex reaction-time task or
      in the digit symbol test of the Wechsler Adult Intelligence Scale. Contrary to
      reference subjects, the TE subjects did not show any improvement or learning
      effect in the digit symbol test over the chamber phases. n-Butyl acetate tended
      to affect cognitive functioning more obviously than toluene did. Suggestion or
      expectancy effects were not observed in any group in the clean-air baseline
      conditions. CONCLUSIONS: The results do not support the notion that men with
      subjective hypersensitivity to chemicals would be more affected than healthy men
      regarding cognitive functioning during annoying solvent exposure below thresholds
      for acute neurotoxic effects.

PMID- 10901115
TI  - Standing at work and progression of carotid atherosclerosis.
AB  - OBJECTIVES: The association between the amount of standing at work and the
      progression of carotid intima media thickness (IMT) was studied among 584 active
      working men participating in the Kuopio Ischemic Heart Disease Risk Factor Study.
      METHODS: Ultrasound measurements of atherosclerotic changes in the carotid
      arteries were performed at the beginning of the study and after 4 years. Analyses
      of changes in IMT included adjustments for risk factors and stratification by
      base-line levels of atherosclerosis and prevalent ischemic heart disease (IHD).
      RESULTS: Significant relationships were found between the amount of standing at
      work and atherosclerotic progression. After adjustment for the heaviness of the
      work, psychosocial job factors, income, and biological and behavioral risk
      factors, the mean change in maximum IMT for those standing not at all, a little,
      a lot, and very much was 0.24, 0.25, 0.28, and 0.33 mm, respectively. For men
      with IHD the respective changes were 0.08, 0.15, 0.37, and 0.75 mm -- a 9-fold
      difference between the no-exposure and high-exposure group. For the men with
      carotid stenosis, the respective difference was 3-fold. CONCLUSIONS: These
      findings provide the first empirical support in a population study for the role
      of hemodynamic factors in the progression of atherosclerosis induced by long-term
      standing. Men with carotid stenosis or IHD appear especially vulnerable to the
      adverse effects associated with standing at work. Reducing the duration of
      standing at work should be considered both in the occupational rehabilitation of
      such patients and in the primary prevention of atherosclerosis.

PMID- 10901116
TI  - Sleep-disordered breathing and occupational accidents.
AB  - OBJECTIVES: The relationship between a common type of sleep disturbance, sleep
      disordered breathing, and the risk of becoming involved in an occupational
      accident was studied. METHODS: A 10-year retrospective comparison was made of
      occupational injuries reported to the Occupational Injury Statistics Division of
      the Swedish National Board of Occupational Safety and Health. The injury rates
      for 704 consecutive patients suffering from sleep-disordered breathing were
      compared with the rates for an employed, age-matched random sample of 580
      subjects, drawn from the general population. RESULTS: The risk of being involved
      in an occupational accident was about 2-fold among male heavy snorers and
      increased by 50% among men suffering from obstructive sleep apnea syndrome
      (OSAS). For females the risk increased by at least 3-fold among heavy snorers and
      OSAS patients. Reduced vigilance and attention due to sleep-disordered breathing
      are the proposed mechanisms behind the results. CONCLUSION: The early
      identification and treatment of persons suffering from sleep-disordered breathing
      would not only have positive impact on individual health and well-being but also
      on occupational safety.

PMID- 10901117
TI  - Occupational determinants for rheumatoid arthritis.
AB  - OBJECTIVES: The aim of the present study was to evaluate possible occupational
      determinants for rheumatoid arthritis according to lifetime occupational history.
      METHODS: The cases were identified retrospectively from 1980 to 1995 at the
      University Hospital in Linkoping, Sweden. The study comprised 422 cases and 859
      randomly selected referents. Exposure data were collected through a postal
      questionnaire. RESULTS: For men, occupations with increased, although
      nonsignificant, odds ratios (OR) were farmers or farm workers [OR 1.8, 95%
      confidence interval (95% CI) 1.0-3.5], textile workers (OR 2.0, 95% CI 0.3-16.2),
      asphalters (OR 14.0, 95% CI 1.2-799.0 without latency requirement), and employees
      at service stations (OR 2.2, 95% CI 0.5-9.5). Among the women, hairdressers and
      beauticians (OR 2.7, 95% CI 0.8-8.6) had an increased risk for rheumatoid
      arthritis, as well as those exposed to hairdressing chemicals (OR 3.0, 95% CI 1.0
      9.4) and meat products (OR 2.0, 95% CI 1.0-4.0). CONCLUSIONS: Several of the
      findings in this study are in accordance with those of previous studies. The
      increased risks of rheumatoid arthritis for asphalters and employees at service
      stations are however new associations previously not described in the literature.

PMID- 10901119
TI  - Radiographic knee osteoarthritis in floorlayers and carpenters.
AB  - OBJECTIVES: The aim of the present study was to examine the relationship between
      knee-straining work and radiological findings of knee osteoarthritis and to study
      the relation between radiological findings and self-reported knee complaints and
      clinical signs of knee osteoarthritis. METHODS: The material consisted of 133
      floorlayers, 506 carpenters, and 327 compositors, 26-72 years of age, who had
      completed a questionnaire and reported no previous knee trauma. A stratified
      sample of these questionnaire respondents, 50 floorlayers, 51 carpenters, and 49
      compositors, were radiologically examined for knee osteoarthritis by 2
      radiologists. The X-ray films were independently assessed by 2 radiologists and
      blinded with respect to knee complaints, trade, and age. RESULTS: The
      radiological investigation showed estimated prevalences of knee-osteoarthritis
      (grades 2-4) for 14% of the floorlayers, 8% of the carpenters, and 6% of the
      compositors (not significantly different). For the subjects > or =50 years of age
      the estimated prevalences of the combination of radiological grades 2-4 for knee
      osteoarthritis and knee complaints during the last 12 months were 29% [95%
      confidence interval (95% CI) 17-44%], 9% (95% CI 1-26%), and 1% (95% CI 1-10%)
      for the floorlayers, carpenters, and compositors, respectively. Radiological
      grades 2-4 were mainly found for subjects above the age of 50 years, subjects
      with knee complaints, and floorlayers. Radiological knee osteoarthritis was
      positively associated with self-reported knee complaints and with clinical signs
      of intraarticular and retropatellar crepitation. CONCLUSIONS: The data suggest
      that work in which a considerable amount of time is spent in knee-straining
      positions may be a risk factor for the development of knee osteoarthritis above
      the age of 50 years.

PMID- 10901118
TI  - Cellulase allergy and challenge tests with cellulase using immunologic
      assessment.
AB  - OBJECTIVES: This study attempted to develop and evaluate a challenge test for
      diagnosing allergic asthma and rhinitis due to cellulase. METHODS: Challenge
      tests in a chamber were performed on 11 persons sensitized to cellulase. Four
      different enzyme-lactose mixtures, starting from a 0.03% mixture, were used. The
      enzyme dust was generated from a dry enzyme preparation mixed with lactose
      powder, using pressurized air. The cellulase concentration in the air was
      measured with an immunochemical method. RESULTS: Nasal, pharyngeal, or bronchial
      symptoms could be elicited at cellulase air concentrations of 1 to 1300
      microg/m3. A dose-response relationship was observed for symptoms in repeated
      challenge tests with increasing concentrations of cellulase. For 2 persons skin
      symptoms could also be reproduced. CONCLUSION: The challenge method proved to be
      a practical means with which to simulate conditions at the worksite and elicit
      the specific respiratory symptoms of the patients.

PMID- 10901120
TI  - Item bias in indices measuring psychosocial work environment and health.
AB  - OBJECTIVES: The main purpose of this study was to demonstrate the relevance of
      testing indices concerning the psychosocial work environment by item bias or
      differential item functioning (DIF) analysis. Especially when the work
      environment for different groups is compared, this kind of construct validation
      is important. As exogenous variables gender, age, and occupational group were
      selected. METHODS: Data were taken from a cross-sectional study of Danish
      employees aged 19-59 years (N=5940). The study was carried out in 1990 and
      followed-up in 1995. RESULTS: Item bias was demonstrated in all indices when
      analyzed in relation to gender, age, and occupational groups of the total
      population. Item bias was much weaker or disappeared as the population was
      divided into main occupational groups and analyzed in relation to the same
      exogenous variables. CONCLUSIONS: For a heterogeneous group of employees, gender,
      age, and occupational status are significant determinants of the response pattern
      in relation to indices of the psychosocial work environment. It was concluded
      that, if the psychosocial work environment for different groups is to be
      compared, indices should always be tested for item bias in relation to the
      exogenous variables included in the final analyses. Indices should only be used
      if there is no item bias. If such indices cannot be constructed, it is suggested
      that researchers either concentrate on constructing indices that are valid in
      subgroups or report results based on single-item analyses.

PMID- 10901121
TI  - Downsizing and industrial restructuring in related to changes in psychosocial
      conditions of work in British Columbia sawmills.
AB  - OBJECTIVES: This paper investigates changes in the psychosocial and physical work
      conditions of the sawmill industry in British Columbia, Canada, over the past 35
      years. METHODS: Shifts in work conditions were examined within the context of
      historical changes in sawmill labor demography and job taxonomy as the industry
      was both downsized and restructured, largely in response to an economic recession
      in the early 1980s. RESULTS AND CONCLUSIONS: Downsizing eliminated approximately
      60% of the work force and 1/4 of sawmill job titles. Although all the job
      categories in restructured sawmills showed increased levels of control, the
      gradient in control across job categories was steeper in 1997 than in 1965; this
      change may have important health implications particularly for the unskilled
      workers in the restructured mills.

PMID- 10901126
TI  - Metabolic profiling of valproic acid by cDNA-expressed human cytochrome P450
      enzymes using negative-ion chemical ionization gas chromatography-mass
      spectrometry.
AB  - A sensitive negative ion chemical ionization (NCI) gas chromatographic-mass
      spectrometric (GC-MS) method was modified for the quantitation of valproic acid
      (VPA) metabolites generated from in vitro cDNA-expressed human microsomal
      cytochrome P450 incubations. The use of the inherent soft ionization nature of
      electron-capture NCI to achieve high sensitivity enabled us to conduct kinetic
      studies using small amounts of recombinant human P450 enzymes. The assay is based
      on the selective ion monitoring of the intense [M-181] fragments of
      pentafluorobenzyl (PFB) esters in the NCI mode, and has the following features:
      (1) a micro-extraction procedure to isolate VPA metabolites from small incubation
      volumes (100 microl); (2) a second step derivatization with tert.
      butyldimethylsilylating reagents to enhance sensitivity for hydroxylated
      metabolites; (3) a short run-time (<30 min) while maintaining full separation of
      15 VPA metabolites by using a narrow-bore non-polar DB-1 column plus a new
      temperature gradient; and (4) good reproducibility and accuracy (intra- and inter
      assay RSDs <15%, bias <15%) by using seven deuterated derivatives of analytes as
      internal standards. The derivatives of mono-and diunsaturated metabolites, like
      the parent drug, produced abundant [M-181](-) ions while the hydroxylated
      metabolites gave an ion at m/z of 273, corresponding to the [M-181](-) ion of the
      tert.-butyldimethylsilyl ethers. In conclusion, the GC-NCI-MS analysis of
      valproate metabolites provided us with a high resolution and sensitivity
      necessary to conduct metabolic and kinetic studies of valproic acid in small
      volume samples typical of the in vitro cDNA-expressed micro-incubation enzymatic
      systems.

PMID- 10901127
TI  - Methods for the determination of seven selective serotonin reuptake inhibitors
      and three active metabolites in human serum using high-performance liquid
      chromatography and gas chromatography.
AB  - This paper describes a set of simple and sensitive multiresidue methods for the
      determination of the specific serotonin reuptake inhibitors (SSRIs) used as
      antidepressant drugs, and some of their respective active metabolites in human
      serum. It involves liquid-liquid extraction procedures followed by gas
      chromatography coupled to nitrogen phosphorus detection or isocratic reversed
      phase high-performance liquid chromatography combined with fluorescence detection
      (HPLC-FL), depending on the analytes. Extraction recoveries were between 71 and
      96% for the eight SSRIs and their metabolites analysed by GC and between 41 and
      77% for the two of them analysed by HPLC. Limits of detection (LODs) and limits
      of quantitation (LOQs) ranged, respectively, from 2.5 to 5 microg/l and from 10
      to 20 microg/l. Intra-assay and inter-assay precision was studied at three and
      four concentration levels, respectively, and was less than 19% for all compounds.
      Accuracy was also satisfactory for all. An excellent linearity was observed from
      the LOQs up to 1000 microg/l for milnacipram and paroxetine and from each LOQ up
      to 400 mg/l for the other compounds. The performance of the methods described
      thus allows the therapeutic drug monitoring of the currently commercialised
      SSRIs.

PMID- 10901128
TI  - High-performance liquid chromatographic analysis of AQ4N, an
      alkylaminoanthraquinone N-oxide.
AB  - A simple, highly selective and reproducible reversed-phase high-performance
      liquid chromatography method has been developed for the analysis of the new anti
      cancer pro-drug AQ4N. The sample pre-treatment involves a simple protein
      precipitation protocol, using methanol. Chromatographic separations were
      performed using a HiChrom HIRPB (25 cmX4.6 mm I.D.) column, with mobile phase of
      acetonitrile-ammonium formate buffer (0.05 M) (22:78, v/v), with final pH
      adjusted to 3.6 with formic acid. The flow-rate was maintained at 1.2 ml min(-1).
      Detection was via photodiode array performed in the UV range at 242 nm and, since
      the compounds are an intense blue colour, in the visible range at 612 nm. The
      structurally related compound mitoxantrone was used as internal standard. The
      validated quantification range of the method was 0.05-10.0 microg ml(-1) in mouse
      plasma. The inter-day relative standard deviations (RSDs) (n=5) ranged from 18.4%
      and 12.1% at 0.05 microg ml(-1) to 2.9% and 3.3% at 10.0 microg ml(-1) for AQ4N
      and AQ4, respectively. The intra-day RSDs for supplemented mouse plasma (n=6)
      ranged from 8.2% and 14.2% at 0.05 microg ml(-1) to 7.6% and 11.5% at 10.0 microg
      ml(-1) for AQ4N and AQ4, respectively. The overall recovery of the procedure for
      AQ4N was 89.4 +/- 1.77% and 76.1 +/- 7.26% for AQ4. The limit of detection was 50
      ng ml(-1) with a 100 microl sample volume. The method described provides a
      suitable technique for the future analysis of low levels of AQ4N and AQ4 in
      clinical samples.

PMID- 10901129
TI  - Determination of moxifloxacin (BAY 12-8039) in plasma and lung tissue by high
      performance liquid chromatography with ultraviolet detection using a fully
      automated extraction method with a new polymeric cartridge.
AB  - The aim of this study was to develop a high-performance liquid chromatographic
      (HPLC) assay for the determination of moxifloxacin in human plasma and lung
      tissue. The assay was based on HPLC with a Supelcosil ABZ+ column and ultraviolet
      detection set at a wavelength of 296 nm. The extraction procedure was
      characterized by a fully automated liquid-solid extraction using an OASIS column
      for the solid phase. The assay has been found to be linear and validated over the
      concentration range 3.2 to 0.025 microg/ml for moxifloxacin in plasma and from 16
      to 0.25 microg/g for moxifloxacin in lung tissue. In future, the assay will
      support the pharmacokinetic study of the penetration of moxifloxacin in human
      lung tissue.

PMID- 10901130
TI  - Determination of quinolones in plasma samples by capillary electrophoresis using
      solid-phase extraction.
AB  - The potential of capillary zone electrophoresis (CZE) and micellar electrokinetic
      capillary chromatography (MEKC) have been investigated for the separation and
      quantitative determination of 10 quinolone antibiotics. The influence of
      different conditions, such as the buffer and pH of the electrolyte, the
      surfactant and the ion-pairing agents added to the electrolyte and the organic
      modifier were studied. A buffer consisting of 40 mM sodium tetraborate at pH 8.1
      containing 10% (v/v) methanol was found to be a highly efficient electrophoretic
      system for separating lomefloxacin, enoxacin, norfloxacin, pipemidic acid,
      ofloxacin, piromidic acid, flumequine, oxolinic acid, cinoxacin and nalidixic
      acid. A solid-phase extraction method to remove the sample matrix (pig plasma
      samples) was developed on a C(18) cartridge using a mixture of methanol-water
      (70:30, v/v). The method is specific and reproducible and mean recoveries were in
      the range 94.0+/-4.2% and 123.3+/-4.1% for pig plasma samples over the range
      used. A linear relationship between concentration and peak area for each compound
      in pig plasma samples was obtained in the concentration range 5-20 mg l(-1) and
      detection limits were between 1.1 and 2.4 mg l(-1).

PMID- 10901131
TI  - Quantification of (+)-calanolide A, a novel and naturally occurring anti-HIV
      agent, by high-performance liquid chromatography in plasma from rat, dog and
      human.
AB  - A HPLC method was validated for quantification of (+)-calanolide A (1), a novel
      anti-HIV agent, in rat, dog and human plasma. The synthetic intermediate (+/-)-12
      oxocalanolide A (2) was found to be a suitable internal standard. Compounds were
      extracted from plasma using a solid-phase C(18) cartridge and quantified over the
      assay range of 12.5 to 800 ng/ml. The method was utilized to determine (+)
      calanolide A pharmacokinetics in rats, dogs and humans. This is the first report
      of a validated HPLC assay for determination of (+)-calanolide A concentrations in
      rat and dog plasma as well as human plasma obtained from clinical trials. There
      was no evidence of in vivo epimerization of (+)-calanolide A to its inactive
      epimer (+)-calanolide B (3).

PMID- 10901132
TI  - Reliable gas chromatographic-mass spectrometric method combined with a headspace
      autosampler for isoflurane determination in blood.
AB  - Isoflurane is a nonflammable, liquid, volatile inhalation anesthetic administered
      by vaporizing. Although it is now commonly used, fatal cases resulting from its
      abuse or misuse have been reported. A combined system of a gas chromatograph-mass
      spectrometer and a headspace autosampler is therefore proposed for the detection
      of blood isoflurane. This analytic method showed sharp and well separated peaks,
      and revealed a good linear relationship (r=0.9994) with a function of y = 7.3768x
      - 0.0222 at concentrations between 18.7 and 299.2 microg/ml. The limits of
      detection and quantitation of this method were 1.2 and 4.7 microg/ml,
      respectively. The within- and between-run precision for spiked samples, assessed
      by the coefficient of variations, ranged from 1.7 to 10.0% and from 4.1 to 12.8%,
      respectively. The within- and between-run accuracy, assessed by errors from
      theoretical values, were 2.2-7.8% and 2.4-9.6%, respectively. In addition,
      practical sample analysis showed a good applicability, with a within-run
      precision rate of 5.6 to 7.7% and a between-run precision rate of 5.2-10.6%. In
      summary, the present work presents a valid alternative for blood isoflurane
      analysis.

PMID- 10901133
TI  - Quantitative analysis of levamisole in porcine tissues by high-performance liquid
      chromatography combined with atmospheric pressure chemical ionization mass
      spectrometry.
AB  - This work presents the development and the validation of an LC-MS-MS method with
      atmospheric pressure chemical ionization for the quantitative determination of
      levamisole, an anthelmintic for veterinary use, in porcine tissue samples. A
      liquid-liquid back extraction procedure using hexane-isoamylalcohol (95:5, v/v)
      as extraction solvent was followed by a solid-phase extraction procedure using an
      SCX column to clean up the tissue samples. Methyllevamisole was used as the
      internal standard. Chromatographic separation was achieved on a LiChrospher 60 RP
      select B (5 microm) column using a mixture of 0.1 M ammonium acetate in water and
      acetonitrile as the mobile phase. The mass spectrometer was operated in MS-MS
      full scanning mode. The method was validated for the analysis of various porcine
      tissues: muscle, kidney, liver, fat and skin plus fat, according to the
      requirements defined by the European Community. Calibration graphs were prepared
      for all tissues and good linearity was achieved over the concentration ranges
      tested (r>0.99 and goodness of fit <10%). Limits of quantification of 5.0 ng/g
      were obtained for the analysis of levamisole in muscle, kidney, fat and skin plus
      fat tissues, and of 50.0 ng/g for liver analysis, which correspond in all cases
      to half the MRLs (maximum residue limits). Limits of detection ranged between 2
      and 4 ng/g tissue. The within-day and between-day precisions (RSD, %) and the
      results for accuracy fell within the ranges specified. The method has been
      successfully used for the quantitative determination of levamisole in tissue
      samples from pigs medicated via drinking water. Moreover the product ion spectra
      of the levamisole peak in spiked and incurred tissue samples were in close
      agreement (based on ion ratio measurements) with those of standard solutions,
      indicating the worthiness of the described method for pure qualitative purposes.

PMID- 10901134
TI  - Effect of 2-deoxy-D-glucose on acetylcholine and histamine levels in gastric
      juice of pylorus-ligated rats anesthetized with urethane.
AB  - Acetylcholine (ACh) in gastric juice was detected and measured by pretreatment of
      acetylcholinesterase inhibitor, 1 mM eserine (1 ml/rat, p.o.), in pylorus-ligated
      rats, by liquid chromatography with electrochemical detection. In order to
      elucidate whether or not the ACh level in gastric juice reflects the activity of
      cholinergic neurons, the effect of 2-deoxy-D-glucose (2-DG), a vagus stimulant,
      on the levels of ACh, histamine and gastric acid in gastric juice was
      investigated in pylorus-ligated rats anesthetized with urethane (1.25 g/kg,
      i.p.). Under the non-anesthetic condition, ACh, histamine and gastric acid levels
      were 100+/-25 pmol/h, 120+/-10 ng/h, and 240+/-32 microequiv./h, respectively.
      These levels were completely inhibited by urethane anesthesia. Under the
      anesthetized condition, 2-DG (50-200 mg/kg, i.v.) significantly increased ACh and
      histamine levels in gastric juice, as well as acid secretion. The 2-DG (200
      mg/kg, i.v.)-induced increases in these levels were completely inhibited by
      vagotomy. These results suggest that ACh level measured in gastric juice reflects
      the activity of cholinergic transmission. Furthermore, these results also support
      the conclusion that vagus stimulation facilitates not only cholinergic
      transmission but also histaminergic transmission related to gastric acid
      secretion.

PMID- 10901135
TI  - Simultaneous determination of urinary free cortisol and 6beta-hydroxycortisol by
      liquid chromatography-atmospheric pressure chemical ionization tandem mass
      spectrometry and its application for estimating hepatic CYP3A induction.
AB  - A reversed-phase high-performance liquid chromatography coupled to atmospheric
      pressure chemical ionization tandem mass spectrometry (HPLC-APCI-MS-MS) assay was
      developed to simultaneously determine monkey urinary free cortisol (C) and 6beta
      hydroxycortisol (6beta-OHC) in 8 min. Urine sample (0.5 ml) containing
      fludrocortisone acetate (F-C) as the internal standard was extracted with ethyl
      acetate for 5 min with an extraction efficiency of 90% and 75% for C and 6beta
      OHC, respectively. A Perkin-Elmer Sciex API 3000 triple quadruple instrument was
      used for mass spectrometric detection and the column eluent was directed to a
      heated nebulizer probe. The assay was linear over the range 0.25-10 microM for
      each analyte. The intra- and inter-day relative standard deviation (RSD) over the
      entire concentration range for both analytes was less than 10%. Accuracy
      determined at three concentrations (0.8, 2.0 and 8.0 microM) ranged between 95.5
      and 108%. The method described herein is suitable for the rapid and efficient
      measurement of 6beta-OHC/C ratio in Rhesus monkey urine following administration
      of known hepatic CYP3A inducers and can be used to estimate potential CYP3A
      induction by drug candidates in the process of early drug development.

PMID- 10901136
TI  - Measurement of free and bound malondialdehyde in plasma by high-performance
      liquid chromatography as the 2,4-dinitrophenylhydrazine derivative.
AB  - We established a method for the detection of free and total (free and bound)
      malondialdehyde (MDA) in human plasma samples after derivatisation with 2,4
      dinitrophenylhydrazine (DNPH). Free MDA was prepared by perchloric acid
      deproteinisation whereas an alkaline hydrolysation step for 30 min at 60 degrees
      C was introduced prior to protein precipitation for the determination of total
      MDA. Derivatisation was accomplished in 10 min at room temperature subsequently
      chromatographed by HPLC on a reversed-phase 3 microm C(18) column with UV
      detection (310 nm). The detection limit was 25 pmol/ml for free and 0.3 nmol/ml
      for total MDA. The recovery of MDA added to different human plasma samples was
      93.6% (n=11; RSD 7.1%) for the hydrolysation procedure. In samples from 12
      healthy volunteers who underwent a hypoxic treatment (13% O2 for 6 h) we
      estimated a baseline value of total MDA of 2.16 nmol/ml (SD 0.29) (ambient air)
      with a significant increase to 2.92 (nmol/ml, SD 0.57; P=0.01) after the end of
      this physiological oxidative stress challenge. Plasma values of free MDA in these
      samples were close to our detection limit. The presented technique can easily
      performed with an isocratic HPLC apparatus and provides highly specific results
      for MDA as do sophisticated GC-MS methods.

PMID- 10901137
TI  - Purification of horse immunoglobulin isotypes based on differential elution
      properties of isotypes from protein A and protein G columns.
AB  - Elution properties of horse immunoglobulin isotypes from protein A and protein G
      columns were examined. IgGa and IgGb isotypes were bound to protein A and protein
      G columns and were eluted by adjusting the pH of the elution buffer from 8.0 to
      2.0. IgGc bound to protein G column but not to protein A column while IgG(T)
      bound to both columns. IgM and IgA apparently appeared not to bind to either
      column. New methods for purification of serum isotypes were developed using
      protein A and protein G columns as well as formerly established methods. Using
      these methods, it was possible to obtain purified isotypes for establishment of
      immunological assays for practical clinical use.

PMID- 10901138
TI  - Simultaneous determination of thioTEPA, TEPA and a novel, recently identified
      thioTEPA metabolite, monochloroTEPA, in urine using capillary gas chromatography.
AB  - An assay for the simultaneous quantitative determination of thioTEPA, TEPA and
      the recently identified metabolite N,N'-diethylene-N"-2-chloroethylphosphoramide
      (monochloroTEPA) in human urine has been developed. MonochloroTEPA was
      synthesized by incubation of TEPA with sodium chloride at pH 8. Thus, with this
      assay monochloroTEPA is quantified as TEPA equivalents. Analysis of the three
      analytes in urine was performed using gas chromatography with selective nitrogen
      phosphorous detection after extraction with a mixture of 1-propanol and
      chloroform from urine samples. Diphenylamine was used as internal standard.
      Recoveries ranged between 70 and 100% and both accuracy and precision were less
      than 15%. Linearity was accomplished in the range of 25-2500 ng/ml for
      monochloroTEPA and 25-5000 ng/ml for thioTEPA and TEPA. MonochloroTEPA proved to
      be stable in urine for at least 4 weeks at -80 degrees C. ThioTEPA, TEPA and
      monochloroTEPA cummulative urinary excretion from two patients treated with
      thioTEPA are presented demonstrating the applicability of the assay for clinical
      samples and that the excreted amount of monochloroTEPA exceeded that of thioTEPA
      on day 2 to 5 of urine collection.

PMID- 10901139
TI  - A new method for determination of serum cholestanol by high-performance liquid
      chromatography with ultraviolet detection.
AB  - We developed a method for the determination of serum 5alpha-cholestan-3beta-ol
      (cholestanol). The sterols were derivatized to the 4'-bromobenzenesulfonyl esters
      and heated in isopropanol. The cholesterol-4'-bromobenzenesulfonate was
      solvolyzed to cholesteryl isopropyl ether, but the derivatized cholestanol did
      not change and could be measured in a high-performance liquid chromatographic
      system equipped with a UV detector at 235 nm. On the other hand, the resulting
      cholesteryl isopropyl ether, having different absorbance and chromatographic
      mobility was not detected. This method was used for measuring cholestanol levels
      in patients with cerebrotendinous xanthomatosis (CTX), liver cirrhosis and serum
      from healthy control subjects. Reproducibility, linearity and recovery tests were
      done on 0.3 ml of serum samples containing >2 microg/ml cholestanol, using
      stigmastanol as an internal standard (I.S.). Determining cholestenol by this
      method can be used for diagnosis and follow-up of patients with CTX and various
      liver diseases.

PMID- 10901140
TI  - Rapid simultaneous determination of glucagon and insulin by capillary
      electrophoresis immunoassays.
AB  - A rapid capillary electrophoresis (CE) with laser-induced fluorescence (LIF)
      competitive immunoassay has been developed for the determination of glucagon in
      biological mixtures. In the assay, fluorescein-conjugated glucagon is mixed with
      the sample followed by addition of anti-glucagon. Free and antibody-bound, tagged
      glucagon could be separated in 3 s using CE to obtain quantitative determination
      of glucagon with a concentration detection limit of 760 pM. The assay was
      combined with a previously developed competitive immunoassay for insulin to
      produce a simultaneous immunoassay for both peptides. The method was used to
      determine glucagon content of islets of Langerhans.

PMID- 10901141
TI  - Determination of nitrate in blood by gas chromatography and gas chromatography
      mass spectrometry.
AB  - We devised a sensitive and simple method for determining nitrate in whole blood,
      using an extractive alkylation technique. Nitrate in whole blood was reduced to
      nitrite by hydrazine sulfate in the presence of Cu2+ and Zn2+ as catalysts, and
      alkylated with pentafluorobenzyl bromide using tetradecyldimethylbenzylammonium
      chloride as the phase-transfer catalyst. The obtained derivative was analyzed
      qualitatively by gas chromatography-mass spectrometry and quantitatively by gas
      chromatography with electron-capture detection. The detection limit of nitrate in
      whole blood was 0.01 mM. The calibration curve was linear over the concentration
      range from 0.02 to 1.0 mM for nitrate in whole blood. The accuracy and precision
      of the method were evaluated and the relative standard deviations were found to
      be within 10%. Using this method, the blood nitrate levels of two victims who
      committed suicide by inhaling automobile exhaust gas were determined.

PMID- 10901142
TI  - Quantitative liquid chromatographic-tandem mass spectrometric determination of
      reserpine in FVB/N mouse plasma using a "chelating" agent (disodium EDTA) for
      releasing protein-bound analytes during 96-well liquid-liquid extraction.
AB  - A sensitive, specific, accurate and reproducible analytical method employing a
      divalent cation chelating agent (disodium EDTA) for sample treatment was
      developed to quantitate reserpine in FVB/N mouse plasma. Samples pretreated with
      40 microl of 2% disodium EDTA in water were extracted by a semi-automated 96-well
      liquid-liquid extraction (LLE) procedure to isolate reserpine and a structural
      analog internal standard (I.S.), rescinnamine, from mouse plasma. The extracts
      were analyzed by turbo ionspray liquid chromatography-tandem mass spectrometry
      (LC-MS-MS) in the positive ion mode. Sample preparation time for conventional LLE
      was dramatically reduced by the semi-automated 96-well LLE approach. The assay
      demonstrated a lower limit of quantitation of 0.02 ng/ml using 0.1-ml plasma
      sample aliquots. The calibration curves were linear from 0.02 to 10 ng/ml for
      reserpine. The intra- and inter-assay precision of quality control (QC) samples
      ranged from 1.75 to 10.9% for reserpine. The intra- and inter-assay accuracy of
      QC samples ranged from -8.17 to 8.61%. Reserpine and the I.S. were found to be
      highly bound to FVB/N mouse plasma protein. This is the first report of disodium
      EDTA employed as a special protein-bound release agent to recover protein-bound
      analytes from plasma. These matrix effects and the effects of pH in the HPLC
      mobile phase on the sensitivities of LC-MS-MS are discussed in this paper.

PMID- 10901143
TI  - High-performance liquid chromatographic method for the determination of
      benzodiazepines in plasma or serum using the column-switching technique.
AB  - A column-switching high-performance liquid chromatographic method for the
      simultaneous determination of five frequently prescribed benzodiazepines:
      clonazepam, diazepam, flunitrazepam, midazolam and oxazepam was developed. A 50
      microl plasma sample was directly injected into a BioTrap 500 MS (hydrophobic
      polymer) column. After a washing step with a mixture of phosphate buffer and
      acetonitrile, the retained benzodiazepines were back-flushed into a reversed
      phase (LiChrospher Select B C8) column with a mobile phase of acetonitrile
      phosphate buffer. The method showed excellent linearity from 50 to 1000 ng/ml for
      clonazepam, flunitrazepam and midazolam and from 50 to 5000 ng/ml for diazepam
      and oxazepam. The recoveries were around 98% for all the benzodiazepines studied.
      The relative standard deviation for between-and within-day assay was <20% for low
      concentrations close to the values of the limit of quantification and <4% for
      high concentrations. The procedure described is relatively simple and rapid
      because no off-line manipulation of the sample is required: the total analysis
      time is approximately 30 min.

PMID- 10901144
TI  - Determination of fenofibric acid in human plasma using automated solid-phase
      extraction coupled to liquid chromatography.
AB  - The pharmacokinetic studies of fenofibrate require a rapid, selective and robust
      method to allow the determination of fenofibric acid, its active metabolite, in
      different biological matrixes (such as plasma, serum or urine). A new fully
      automated method for the determination of fenofibric acid in plasma has been
      developed, which involves the solid-phase extraction (SPE) of the analyte from
      plasma on disposable extraction cartridges (DECs) and reversed-phase HPLC with UV
      detection. The SPE operations were performed automatically by means of a sample
      processor equipped with a robotic arm (ASPEC system). The DEC filled with
      octadecyl silica was first conditioned with methanol and pH 7.4 phosphate buffer.
      A 0.8-ml volume of diluted plasma sample containing the internal standard
      (sulindac) was then applied on the DEC. The washing step was performed with the
      same buffer (pH 7.4). Finally, the analytes were successively eluted with
      methanol (1.0 ml) and 0.04 M phosphoric acid (1.0 ml). After a mixing step, 100
      microl of the resultant extract was directly introduced into the HPLC system. The
      liquid chromatographic (LC) separation of the analytes was achieved on a
      Nucleosil RP-8 stationary phase (5 microm). The mobile phase consisted of a
      mixture of methanol and 0.04 M phosphoric acid (60:40, v/v). The analyte was
      monitored photometrically at 288 nm. The method developed was validated. In these
      conditions, the absolute recovery of fenofibric acid was close to 100% and a
      linear calibration curve was obtained in the concentration range from 0.25 to 20
      microg/ml. The mean RSD values for repeatability and intermediate precision were
      1.7 and 3.9% for fenofibric acid. The method developed was successfully used to
      investigate the bioequivalence between a micronized fenofibrate capsule
      formulation and a fenofibrate Lidose formulation.

PMID- 10901145
TI  - Separation and detection techniques for peptides and proteins in stability
      research and bioanalysis.
AB  - In this paper, a brief overview of the most commonly used methods for the
      separation and analysis of peptides and proteins in stability and bioanalysis
      studies is presented. To investigate the physical stability of peptides and
      proteins, size-exclusion chromatography and electrophoretic separation techniques
      are being used, apart from several other methods. To determine the chemical
      stability of these compounds, separation systems are also important, with
      informative detection modes, such as various spectroscopic detections,
      electrochemical detection and mass spectrometric detection. For the bioanalysis
      of peptides, separation is the most important factor, while the detection must be
      done at the highest possible level of sensitivity.

PMID- 10901146
TI  - Capillary gel electrophoresis: separation of major erythrocyte membrane proteins.
AB  - A new separation method of human erythrocyte membrane proteins by sodium dodecyl
      sulfate capillary gel electrophoresis (SDS-CGE) is described. In this method, a
      replaceable gel matrix was used. Seven major erythrocyte membrane proteins, alpha
      and beta-spectrin, ankyrin 2.1, band 3 (anion-exchanger), 4.1a and b, and 4.2
      (pallidin), were separated and identified by SDS-CGE method. High reproducible
      migration times of these proteins (inter-assay coefficients of variation less
      than 2%), as well as quantification (inter-assay coefficients of variation less
      than 11%) were obtained. This new SDS-CGE method may provide important diagnostic
      evidence for hereditary spherocytosis. It can be a powerful diagnostic tool in
      place of SDS polyacrylamide gel electrophoresis for erythrocyte membrane protein
      analysis.

PMID- 10901147
TI  - Sodium dodecyl sulphate gel electrophoretic preparation of protein standard human
      apolipoprotein B-48.
AB  - Quantitation of plasma apo B-48 is currently performed by densitometric analysis
      of SDS-PAGE zones stained with Coomassie Brilliant Blue, using standard solutions
      of purified apo B-48. Here, preparative gel electrophoresis with a continuous
      elution system was used for purifying apo B-48. A chylomicron fraction was
      isolated by 107,000 g ultracentrifugation of a chylous ascite. The proteins were
      delipidated and precipitated in ethanol-diethyl ether (3:1, v/v), subjected to
      preparative electrophoresis in a 5% polyacrylamide gel and eluted in 0.1% SDS.
      The peak containing apo B-48 was eluted at a retention time of 445-480 min. The
      purity of apo B-48 in this fraction was assessed by the detection of a single
      band (M(r) 260,000) after silver staining and Coomassie staining of 4-15%
      gradient SDS-PAGE. It was confirmed by the absence of apo B-100 contaminant in
      Western blot of the purified protein preparation. A linear relationship was
      observed between the densitometric analysis of SDS-PAGE bands and the apo B-48 in
      a protein range of 0-3 microg. In conclusion, preparative gel electrophoresis was
      used in a single step purification of apo B-48 that was adapted to the
      preparation of a standard solution.

PMID- 10901148
TI  - Rapid and sensitive high-performance liquid chromatographic method for busulfan
      assay in plasma.
AB  - A reversed-phase liquid chromatographic method with ultraviolet detection has
      been developed to determine busulfan concentrations in plasma of children
      undergoing bone marrow transplantation. Plasma samples (200 microl) containing
      busulfan and 1,6-bis(methanesulfonyloxy)hexane as an internal standard were
      prepared by a simple derivatization method with diethyldithiocarbamate followed
      by extraction with ethyl acetate and solid-phase purification on C8 columns
      conditioned with methanol and water and eluted with acetonitrile (recovery 99%).
      Chromatography was accomplished using a Hypersil octadecylsilyl column (10 cm x
      4.6 mm I.D.) and a mobile phase of acetonitrile, tetrahydrofuran and distilled
      water (65:5:30, v/v). The limit of detection was 25 ng/ml (signal-to-noise ratio
      of 5). Calibration curves were linear up to 25,000 ng/ml. Intra-day and inter-day
      coefficients of variation of the assay were < or =5%. This method was used to
      analyse busulfan plasma concentrations after oral administration within the
      framework of therapeutic drug monitoring and pharmacokinetic studies in children.

PMID- 10901149
TI  - Reversed-phase high-performance liquid chromatographic analysis of atenolol
      enantiomers in rat hepatic microsome after chiral derivatizaton with 2,3,4,6,
      tetra-O-acetyl-beta-D-glycopyranosyl isothiocyanate.
AB  - A reversed-phase high-performance liquid chromatographic method for the
      determination of the enantiomers of atenolol in rat hepatic microsome has been
      developed. Racemic atenolol was extracted from alkalinized rat hepatic microsome
      by ethyl acetate. The organic layer was dried with anhydrous sodium sulfate and
      evaporated using a gentle stream of air. Atenolol racemic compound was
      derivatized with 2,3,4,6-tetra-O-acetyl-beta-D-glycopyranosyl isothiocyanate at
      35 degrees C for 30 min to form diastereomers. After removal of excess solvent,
      the diastereomers were dissolved in phosphate buffer (pH 4.6)-acetonitrile
      (50:30). The diastereomers were separated on a Shimadzu CLC-C18 column (10 microm
      particle size, 10 cm x 0.46 cm I.D.) with a mobile phase of phosphate buffer
      methanol-acetonitrile (50:20:30, v/v) at a flow-rate of 0.5 ml/min. A UV-VIS
      detector was operated at 254 nm. For each enantiomer, the limit of detection was
      0.055 microg/ml (signal-to-noise ratio 3) and the limit of quantification (signal
      to-noise ratio 10) was 0.145 microg/ml (RSD <10%). In the range 0.145-20
      microg/ml, intra-day coefficients of variation were 1.0-7.0% and inter-day
      coefficients of variation were 0.4-16.5% for each enantiomer. The assay was
      applied to determine the concentrations of atenolol enantiomers in rat hepatic
      microsome as a function of time after incubation of racemic atenolol.

PMID- 10901150
TI  - Capillary zone electrophoresis for the determination of atovaquone in serum.
AB  - A rapid and simple capillary zone electrophoresis (CZE) method has been developed
      for the determination of atovaquone in serum. The drug was extracted from equine
      serum-chloroform (1:3, v/v) at greater than 80% recovery and assayed in buffer
      containing 25 mM sodium borate (pH 9.1) and 25% acetonitrile. A 100 microm I.D.
      fused-silica capillary was used and the detection was by UV-diode array at 254
      nm; the migration time was approximately 8 min. Intra- and inter-assay
      variabilities were less than 7.8% and 5.8%, respectively, and the accuracy of the
      assay (expressed as % bias) ranged from 4.5 to -5.2%. The working assay range was
      from 2 to 100 microg/ml. This sensitivity could be increased by concentrating
      during the extraction procedure. Replacement of acetonitrile with 75 mM
      surfactant 3-(dimethyldodecylammonio)propanesulfonate gave similar sensitivity
      and provided an additional option to facilitate the separation of atovaquone on
      multiple-drug samples.

PMID- 10901151
TI  - Determination of urea, allantoin and lysine pyroglutamate in cosmetic samples by
      hydrophilic interaction chromatography.
AB  - A new HPLC method using a Polyhydroxyethyl A column involving hydrophilic
      interaction chromatography (HILIC) is described for the simultaneous
      determination of urea, allantoin and lysine pyroglutamate in a cosmetic cream.
      Validation of the method was accomplished with respect to linearity,
      repeatability and limits of detection/quantification. Compound recoveries
      approach 100% with acceptable RSD values. The method is very simple since no
      derivatisation is necessary. Furthermore, it allows the rapid and direct
      chromatographic analysis of urea and hence could provide an alternative to other
      methods used to determine this compound in biological or cosmetic samples.

PMID- 10901152
TI  - Simultaneous high-performance liquid chromatographic determination of the
      antiretroviral agents amprenavir, nelfinavir, ritonavir, saquinavir, delavirdine
      and efavirenz in human plasma.
AB  - This article describes a method for the simultaneous determination of four
      licensed HIV protease inhibitors (amprenavir, nelfinavir, saquinavir and
      ritonavir) and two novel non-nucleoside reverse transcriptase inhibitors
      (efavirenz and delavirdine) in human plasma in a single run. Plasma samples (500
      microl) were treated by liquid-liquid extraction with methyl tert.-butyl ether.
      The compounds were separated by reversed-phase liquid chromatography on a C(18)
      column with spectrophotometric detection at 260 nm. The method is linear over the
      specific ranges investigated, accurate (inaccuracy <11.7%) and showed intra-day
      and inter-day precision within the ranges of 0.9-7.0 and 1.9-8.8%, respectively.
      The six compounds were stable in plasma after 6 months of storage at -20 degrees
      C and after five freeze-thaw cycles.

PMID- 10901153
TI  - The need for new and better antidepressants: reboxetine a new option.
AB  - The selective serotonin reuptake inhibitors (SSRIs) have obtained global
      attention but have not demonstrated superior efficacy in major depression
      compared with older tricyclic antidepressants. From a pharmacological viewpoint
      the noradrenergic system in the brain appears to have a central role in
      neurotransmitter organization. The importance of noradrenaline in depression is
      supported by its association with clinical parameters such as vigilance and
      drive. Reboxetine is a selective noradrenaline reuptake inhibitor--the first in
      its class to be marketed. In both preclinical and clinical studies reboxetine has
      been found to be an effective and safe antidepressant. Furthermore, reboxetine
      restores a patients' social functioning, producing a better quality of remission
      than fluoxetine.

PMID- 10901154
TI  - Antidepressant drugs: does it matter if they inhibit the reuptake of
      noradrenaline or serotonin?
AB  - The current popularity of the selective serotonin reuptake inhibitors (SSRIs) for
      the treatment of depression should not conceal the fact that noradrenergic
      neurones also seem to influence depressed mood. Selective noradrenaline reuptake
      inhibitors (NRIs) such as reboxetine thus seem to be at least as effective as the
      SSRIs. It has been suggested that NRIs influence depression by indirectly
      facilitating serotonergic transmission, or that SSRIs act by facilitating
      noradrenaline; however, the marked differences between SSRIs and NRIs with
      respect to effects and side-effect profile do not support any of these
      assumptions, but rather suggest that SSRIs and NRIs influence depression by
      parallel, independent pathways. In this review the possibility that certain
      symptoms within the depressive syndrome (and certain subtypes of depression)
      respond better to NRIs, whereas other symptoms (and subtypes) respond better to
      SSRIs, will be discussed. In addition, the putative usefulness of NRIs for
      indications other than depression will be commented upon.

PMID- 10901155
TI  - Brain noradrenaline and the mechanisms of action of antidepressant drugs.
AB  - The basic mechanisms of action of presently used antidepressant drugs are still
      far from understood. This review will address a few critical issues in this area,
      namely (i) putative mechanisms underlying the delay in onset of action of
      monoamine reuptake inhibitors and potential limitations to the efficacy of these
      drugs, (ii) the significance of stress-induced activation of the locus coeruleus
      noradrenergic system for the function of the mesolimbic reward system and the
      effect of chronic antidepressant treatment within this context and (iii) the
      interaction between brain noradrenaline and 5-hydroxytryptamine systems and its
      significance for antidepressant drug action. Recent preclinical and clinical
      research which suggest novel strategies to enhance antidepressant drug efficacy
      will also be discussed. From this review emerges the notion that facilitation of
      brain noradrenergic neurotransmission may represent a more fundamental means to
      achieve maximal response in major depression than hitherto understood.

PMID- 10901156
TI  - Noradrenaline and serotonin reuptake inhibition as clinical principles: a review
      of antidepressant efficacy.
AB  - Imipramine and other subsequently developed antidepressants produce numerous
      neurochemical effects, some of which presumably represent active antidepressant
      principles. Numerous studies have compared the efficacy of selective serotonin
      reuptake inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NRIs) with
      variable selectivity, such as desipramine, lofepramine, viloxazine, maprotiline
      or oxaprotiline. Most studies have failed to show differences in response rates
      or subtype responsivity. However, in some studies NRIs appear to be superior to
      SSRIs as regards retardation and, conversely, SSRIs appear superior as regards
      anxiety symptoms. Furthermore, NRIs may be more effective than SSRIs in severe
      depression. The novel selective NRI reboxetine has been shown to be at least as
      effective as imipramine, desipramine and fluoxetine in the treatment of major
      depression. Moreover, reboxetine may also improve social functioning
      significantly more than fluoxetine providing a better quality of the remission.

PMID- 10901157
TI  - Reboxetine: tolerability and safety profile in patients with major depression.
AB  - Since reboxetine acts selectively on the reuptake of noradrenaline, it has a
      different side-effects profile than drugs acting predominantly on the serotonin
      reuptake mechanism. Data from patients treated with reboxetine (n = 1503) or
      placebo/comparator drugs (n = 1027) show that reboxetine has no significant
      cardiovascular effects, a low potential for drug interactions, causes no
      significant impairment of cognitive or motor function and no increase in suicidal
      ideation. In contrast to certain serotonergic drugs, there is no evidence of any
      withdrawal syndrome upon abrupt discontinuation or tapering of reboxetine
      treatment. Sexual dysfunction appears in only a small fraction of the patients
      and mainly with doses higher than 8 mg daily. The rate of discontinuation due to
      adverse effects with reboxetine was not significantly different from that
      observed with placebo in short-term studies. The level of efficacy and apparently
      favourable tolerability profile makes reboxetine an important alternative in the
      medical treatment of depressive illness.

PMID- 10901158
TI  - Outcome measures of antidepressive therapy.
AB  - A variety of outcome measures assessing antidepressive therapy are available.
      However, in randomized clinical trials, the Hamilton Rating Scale for Depression
      (HAM-D) is often the primary outcome measure. Results from factor analysis and
      Rasch item analysis indicate that the HAM-D is heterogeneous and that the sum of
      items scores may not be an adequate measure of the severity of depression. A
      Melancholia Scale of 11 items has been suggested as a more valid measure of the
      core symptoms of affective syndrome. Other global outcome measures, focusing on
      health-related quality of life issues and on social functioning as well as macro
      economic analyses are also used in depression. Applying stringent and well
      documented outcome measures in randomized clinical trials of antidepressants may
      give the clinician a better indication of the most appropriate drug for treatment
      of the individual patient.

PMID- 10901159
TI  - Reboxetine: its effects as measured by the Social Adaptation Self-evaluation
      Scale.
AB  - The determination of the outcome of treatment for depression is important both
      for the symptoms of depression and social functioning. The aim of this review is
      to evaluate the outcome of two clinical trials comparing reboxetine and
      fluoxetine on depressive symptoms and social functioning. These studies used both
      conventional measures of outcome such as the Hamilton Rating Scale for Depression
      (HAM-D) and the Social Adaptation Self-evaluation Scale (SASS), a patient
      centred, disease non-specific scale of social functioning, which was developed
      for measuring social functioning in depressed people. These findings, set against
      a background of all studies in which antidepressants have been compared using
      quality of life instruments, suggest that while some patients may appear to the
      clinician to have recovered, they may remain less than fully well and differences
      in selectivity for neurotransmitter systems may play a part in the degree of
      wellbeing that recovered patients might expect.

PMID- 10901160
TI  - Inhibition of NFkappaB by methyl chlorogenate from Eriobotrya japonica.
AB  - Methylchlorogenic acid (MC) is one of the main components in the leaves of
      Eriobotrya japonica. We previously reported that MC is the most potent
      antioxidant among several components of Eriobotrya japonica, and its antioxidant
      activity is stronger than that of chlorogenic acid. Antioxidants are expected to
      inhibit redox-sensitive NFkappaB activation since NFkappaB is readily influenced
      by cellular oxidative state. Based on these findings, in vivo experiments with MC
      were conducted to determine its ability to downregulate the NFkappaB activation
      in mouse liver. Results clearly showed that MC is a potent suppressor of BHP
      induced NFkappaB activation. We observed a significant reduction by MC on BHP
      induced translocation of p65 subunit of NFkappaB. This may be due to formation of
      p50/p65 heterodimer, which is mainly inducible NFkappaB. MC slightly blocked the
      BHP-induced IkappaB alpha degradation. There is a possibility of IkappaB alpha
      resynthesis via activated NFkappaB during a 5 h waiting period following BHP
      injection. The present results suggest that MC may inhibit NFkappaB activation,
      exhibiting its ability to downregulate the NFkappaB-dependent gene expression.
      Thus, it can be expected that MC may have potential for therapeutic intervention
      on various NFkappaB-dependent pathological conditions such as inflammatory or
      possibly mutagenic processes.

PMID- 10901161
TI  - Activation of c-jun N-terminal kinase by 4-1BB (CD137), a T cell co-stimulatory
      molecule.
AB  - It has been widely accepted that T cell activation requires two signals; one from
      the binding of the antigen/major histocompatibility complex to the T-cell
      receptor (TCR)/CD3 complex and the other from the interaction between a surface
      molecule on antigen presenting cells and its receptor on T cells. The second
      signal is considered as co-stimulatory and the B7/CD28 pair has been well studied
      as a prototype. Recently 4-1BB (CD137) has been characterized as another co
      stimulatory molecule for T cell activation. However, unlike the CD28/B7 pair, 4
      1BB and its ligand 4-1BBL constitute a member of the tumor necrosis factor (TNF)
      receptor/TNF pair superfamily. The signaling mechanism of 4-1BB has not been
      revealed in detail. To investigate whether 4-1BB takes the signaling pathways
      analogous to those for TNF receptors, we generated polyclonal antibodies against
      human 4-1BB and 4-1BBL and established stable transfectants of the receptor and
      the ligand with a high level of cell surface expression. Over-expression of h4
      1BB was found to result in the activation of c-Jun N-terminal kinase (JNK) in the
      human embryonic kidney cell line 293. In T cells, it has been previously
      demonstrated that JNK activation requires dual signals such as the ligation of
      TCR/CD3 complex plus CD28 co-stimulation or PMA plus ionomycin. The JNK
      activation by 4-1BB in Jurkat T cells was also found to require stimulation of
      the TCR/CD3 complex, consistent with the notion that 4-1BB functions as a co
      stimulatory molecule for T cell activation.

PMID- 10901162
TI  - Inhibitory effect of Artemisia asiatica alkaloids on acetylcholinesterase
      activity from rat PC12 cells.
AB  - We screened 42 Korean traditional tea plants to determine the inhibitory effect
      of acetylcholinesterase and attenuation of toxicity induced by amyloid-beta
      peptide, which were related to the treatment of Alzheimer's disease (AD). The
      methanolic extract from Artemisia asiatica among tested 42 tea plants, showed the
      highest inhibitory effect (48%) on acetylcholinesterase in vitro. The methanolic
      extract was further separated with n-hexane, chloroform, and ethyl acetate of
      water, in order. The chloroform solubles, which were high in inhibitory effect of
      acetylcholinesterase, were repeatedly subjected to open column chromatography on
      silica gel. From the highest inhibitory fraction (78%) on acetylcholinesterase,
      the single compound was obtained by the Sep-Pak Cartridge (C18: reverse phase
      column). This compound was found to react positively on Dragendorff's reagent
      (potassium bismuth iodide), which typically reacted with the alkaloid. This
      compound was purified by HPLC (mu-bondapack C18 reverse phase column: 3.9 x 150
      mm). The IC50 (the concentration of 50% enzyme inhibition) value of this compound
      was 23 micrograms/ml and the inhibitory pattern on acetylcholinesterase was mixed
      with competitive/non-competitive type. We examined the effects of this compound
      on toxicity induced by A beta (25-35) in rat pheochromocytoma PC12 cells.
      Pretreatment of the PC12 cells for 2 h with an alkaloid of Artemisia asiatica
      (1200 microg/ml) reduced the toxicity induced by A beta. This study demonstrated
      that an alkaloid of Artemisia asiatica, which was metabolized to small molecule
      in digestive tract and then could pass through the blood-brain barrier, appeared
      to be an acetylcholinesterase inhibitor with a blocker of neurotoxicity induced
      by A beta in human brain causing Alzheimer's disease.

PMID- 10901163
TI  - Genetic engineering of drought resistant potato plants by introduction of the
      trehalose-6-phosphate synthase (TPS1) gene from Saccharomyces cerevisiae.
AB  - In yeast, trehalose-6-phosphate synthase is a key enzyme for trehalose
      biosynthesis, encoded by the structural gene TPS1. Trehalose affects sugar
      metabolism as well as osmoprotection against several environmental stresses, such
      as heat and desiccation. The TPS1 gene of Saccharomyces cerevisiae was engineered
      under the control of the CaMV 35S promoter for constitutive expression in
      transgenic potato plants by Ti-plasmid of Agrobacterium-mediated transformation.
      The resulting TPS1 transgenic potato plants exhibited various morphological
      phenotypes in culture tubes, ranging from normal to severely retarded growth,
      including dwarfish growth, yellowish lancet-shaped leaves, and aberrant root
      development. However, the plants recovered from these negative growth effects
      when grown in a soil mixture. The TPS1 transgenic potato plants showed
      significantly increased drought resistance. These results suggest that the
      production of trehalose not only affects plant development but also improves
      drought tolerance.

PMID- 10901164
TI  - Cloning and sequencing of cel5Z gene from Erwinia chrysanthemi PY35.
AB  - The phytopathogenic bacterium Erwinia chrysanthemi (Ech) secretes multiple
      isozymes of plant cell wall disrupting enzymes such as pectate lyase and
      endoglucanases. We cloned genomic DNA from Ech PY35 digested with Sau3AI and
      ligated into pBluescript II SK+. One of the E. coli XL1-blue clones had the
      ability to hydrolyze carboxymethyl cellulose and polygalacturonic acid. By
      subsequent subcloning from this 2.9 kb fragment, we obtained a 2.0 kb (pPY401),
      designated cel5Z, which had the activity of hydrolyzation of carboxymethyl
      cellulose. The cel5Z gene had an open reading frame (ORF) of 1,281 bp starting
      with an ATG start codon and followed by a TAA stop codon, encoding 426 amino
      acids with a signal peptide of 41 amino acids. Since the deduced amino acid
      sequence of this protein was very similar to that of CelE of Pseudomonas
      fluorescens, and had the conserved region, VIYEIYNEPL, it belonged to the
      glycoside hydrolase family 5 of EC 3.2.1.4. The molecular mass of Cel5Z protein
      from E. coli XL1-blue, as analyzed by CMC-SDS-PAGE, appeared to be 42 kDa. The
      optimum pH was 6, and the optimum temperature was about 40 degrees C for its
      enzymatic activity.

PMID- 10901165
TI  - Identification of p53 gene mutations in breast cancers and their effects on
      transcriptional activation function.
AB  - Somatic mutations in the p53 tumor suppressor gene are the most common genetic
      alterations found in human malignancies. In the present study, we studied 36
      primary human breast carcinomas, using a polymerase chain reaction-single-strand
      conformation polymorphism (PCR-SSCP) and sequencing analysis of exons 2 through 9
      for the presence of p53 gene mutations. Six of 36 (17%) breast cancers contained
      mutations within the core domain of the p53 protein responsible for sequence
      specific DNA binding (codons 102-292); all 5 missense mutations clustered between
      codons 240 and 291 (codons 240, 243, 250, 285, and 291), whereas one nonsense
      mutation occurred at codon 199. By using recombinant PCR in vitro mutagenesis, we
      introduced point mutations at codons 199 from Gly to stop (gly199stop), 240 from
      Ser to Ile (ser240Ile), 250 from Pro to Ala (pro250ala), 285 from Glu to Lys
      (glu285lys), and 291 from Lys to Asn (lys291asn), and all the p53 sequences were
      subcloned into the CMVneoBam vector under the control of the cytomegalovirus
      (CMV) promoter. To test whether the mutants p53 were functionally wild-type (wt)
      or mutant, we transfected them to p53-null Saos-2 cells with a reporter plasmid
      containing a p53-responsive element, and performed chloramphenicol
      acetyltransferase (CAT) assay. Transient CAT assay for transcriptional activation
      revealed that one group, including gly199stop, ser240ile, glu285lys, and
      lys291asn, abolished the transcriptional activity, whereas the other group,
      including pro250ala, retained stronger transcriptional transactivation activity
      than that of wt p53.

PMID- 10901166
TI  - Reporter constructs showing proper globin gene switching in cultured erythroid
      cell lines.
AB  - Recent advances in the study of globin gene switching in the context of complete
      gene locus have contributed greatly to our understanding of developmental
      regulation mechanism of globin gene expression. However, it is not clear yet
      whether the cluster is sufficient in proper gene switching when the globin genes
      are replaced with conventional reporter genes. Furthermore, even though erythroid
      specific and ubiquitous transcription factors involved in erythroid-specific
      globin gene expression have been characterized and some plausible globin gene
      switching models have been suggested, any specific factor directly involved in
      globin gene switching is not yet identified. In this study, as an effort to
      further understand globin switching mechanism and to identify globin switching
      factors, we constructed reporter vectors by juxtaposing several putative
      regulatory elements in human beta-globin locus to conventional reporter genes and
      analyzed their stage-specific expression in erythroid cell lines. At the end, we
      demonstrated that gammabeta-type constructs, in which both gamma-type and beta
      type globin reporter genes were linked in cis below beta-globin locus control
      region (LCR), show proper stage-specific reporter gene expression in erythroid
      cell lines and also recapitulate globin switching in cell hybrids.

PMID- 10901167
TI  - Progression of hepatic stellate cell activation is associated with the level of
      oxidative stress rather than cytokines during CCl4-induced fibrogenesis.
AB  - In order to identify a fibrogenic factor associated with the potential of hepatic
      stellate cells (HSC) activation that arises during the CCl4-induced fibrogenic
      process, the relationship between the activation of HSC and levels of several
      fibrogenic factors were investigated. After isolation of HSC from the liver at
      different stages of CCl4 intoxication, the activation of HSC was assessed by the
      expression of alpha-smooth muscle actin. Levels of cytokines and oxidative stress
      in liver homogenates and plasma were measured by enzyme linked immunosorbent
      assay and the colorimetric method. In primary culture, HSC isolated from a rat
      liver were gradually activated in a time-dependent manner according to CCl4
      administration. The progression of HSC activation was closely correlated with
      parameters related to oxidative stress in liver homogenates rather than the
      tissue levels of several cytokines. Also, the levels of antioxidants and arginase
      activity were inversely correlated with HSC activation. In plasma, the levels of
      oxidative stress and cytokines in CCl4-treated rat livers were not associated
      with the activation of HSC found during the CCl4-induced fibrogenic process. The
      relationship between HSC activation and oxidative stress was also confirmed
      through several factor-treated HSC cultures. In conclusion, the activation of HSC
      was accelerated according to CCl4 administration, and the progression of HSC
      activation is absolutely related to the oxidative stress. These results show that
      enhanced oxidative stress is an important signal for activation of HSC in
      experimental liver fibrogenesis.

PMID- 10901168
TI  - Saccharomyces cerevisiae Ste5 is important for induction and substrate
      specificity of Fus3 MAP kinase in the pheromone signaling pathway.
AB  - The pheromone pathway is one of the mitogen activated protein kinase (MAPK)
      signaling pathways identified in Saccharomyces cerevisiae and is involved in both
      G1 cell cycle arrest and mating of cells. Fus3 functions at a branching point for
      G1 cell cycle arrest and mating responses in the signaling cascade, and the Fus3
      MAPK uses components of both G1 arrest and mating routes as substrates. The Ste5
      is a scaffold protein of the MAPK module and is essential for the activation of
      Fus3. However, it is not known how Ste5 is involved in the specific activation of
      Fus3 in G1 arrest and mating. In this study, we characterized several G1 arrest
      defective Ste5 mutants to better understand the roles of Ste5 in the regulation
      of Fus3. The level of Fus3 increased by treatment with alpha-factor. However, the
      alpha-factor effects were not readily apparent in the observation of yeast cells
      containing G1 arrest defective ste5 mutant. This suggests that Ste5 plays an
      essential role in Fus3 induction. Fus3 immune kinase assay of G1 arrest defective
      ste5 transformants revealed that Ste5 is important for substrate specificity of
      Fus3 for G1 arrest and/or mating.

PMID- 10901169
TI  - Molecular genetic analysis of apm-2 and aps-2, genes encoding the medium and
      small chains of the AP-2 clathrin-associated protein complex in the nematode
      Caenorhabditis elegans.
AB  - In this report, we analyzed the apm-2 and aps-2 genes, which encode the nematode
      homologues of the medium chain and the small chain of the plasma membrane
      associated clathrin-associated protein complex AP-2, respectively. We determined
      the genomic structure of the two genes. We show that apm-2 and aps-2 genes are
      expressed in most, if not all, cells during embryogenesis, and that the two genes
      are expressed primarily in neurons and some hypodermal cells following hatching
      through adulthood. RNA interference experiments showed that the reduction of
      either apm-2 or aps-2 gene function causes embryonic lethality, larval lethality
      at various stages of development, and other morphological defects in the larval
      stages. These results indicate that apm-2 and aps-2 gene functions are required
      during both embryogenesis and larval stages, and that their functions may be
      required in proper neuronal functions.

PMID- 10901170
TI  - Cloning and characterization of ntTMK1 gene encoding a TMK1-homologous receptor
      like kinase in tobacco.
AB  - A cDNA encoding a receptor-like kinase, designated NtTMK1, was isolated from
      Nicotiana tabacum. The kinase domain of NtTMK1 contained all of 12 subdomains and
      invariant amino acid residues found in eukaryotic protein kinases. The
      extracellular domain contained 11 leucine-rich repeats which have been implicated
      in protein-protein interactions. The amino acid sequence of NtTMK1 exhibited high
      homology with those of TMK1 of Arabidopsis and TMK of rice in both kinase and
      extracellular domains, suggesting that NtTMK1 is a TMK homologue of tobacco. The
      NtTMK1 transcripts were present in all major plant organs, but its level varied
      in different developmental stages in anthers and floral organs. NtTMK1 mRNA
      accumulation in leaves was stimulated by CaCl2, methyl jasmonate, wounding,
      fungal elicitors, chitins, and chitosan. The NtTMK1 mRNA level also increased
      upon infection with tobacco mosaic virus.

PMID- 10901171
TI  - Differential effects of cholera toxin and pertussis toxin on the c-fos and c-jun
      mRNA expression in rat C6 glioma cells.
AB  - Cholera toxin (CTX) increased c-fos mRNA level whereas it down-regulated the c
      jun mRNA level in rat C6 glioma cells. In contrast to the action of CTX,
      pertussis toxin (PTX) did not affect either c-fos or c-jun mRNA level. The
      elevated c-fos mRNA level induced by CTX was significantly inhibited by the co
      treatment with dexamethasone (DEX). However, DEX did not affect CTX-induced down
      regulation of c-jun mRNA level. Cycloheximide (CHX) increased c-fos and c-jun
      mRNA levels. CHX caused a super-induction of CTX-induced c-fos mRNA level. Our
      results suggest that CTX-, but not PTX-, sensitive G-proteins may play an
      important role for c-fos mRNA up-regulation and c-jun mRNA down-regulation. In
      addition, DEX appears to have a selective inhibitory action against c-fos mRNA
      expression regulated by CTX. Ongoing protein synthesis inhibition is required for
      the superinduction of c-fos, but not c-jun, mRNA induced by CTX.

PMID- 10901172
TI  - Cytoprotective effect of arginine deiminase on taxol-induced apoptosis in DU145
      human prostate cancer cells.
AB  - We purified and partially sequenced a cytostatic protein from the ASC-17D Sertoli
      cell-conditioned media (rSCCM) showing a molecular weight of 90 kDa with
      homodimeric composition. N-terminal amino acid analysis revealed that the protein
      was homologous to the arginine deiminase (ADI) of Mycoplasma arginini. We found
      ADI enzyme activity in rSCCM and the abolishment of the growth inhibitory effect
      by the supplement of L-arginine. Thus, we confirmed that the cytostatic activity
      in rSCCM was due to the depletion of extracellular L-arginine by ADI. Apparent
      increase of cell death or DNA fragmentation was not observed in DU145 cells
      cultured in the presence of ADI. Incubation of DU145 cancer cells with taxol
      resulted in a marked DNA fragmentation, whereas pretreatment with ADI or
      cycloheximide protected the cells from taxol-induced apoptosis. Preincubation of
      the cells with ADI inhibited S35-methionine incorporation into protein synthesis
      in a dose dependent manner. These data suggest that ADI-induced arginine
      depletion may inhibit protein synthesis, and result in the protection of
      apoptotic cell death that requires new protein synthesis.

PMID- 10901173
TI  - Analysis of expressed sequence tags of Porphyra yezoensis.
AB  - Single direct partial sequencing of anonymous cDNA clones was performed to obtain
      genetic information on red algae Porphyra yezoensis of which genetic information
      is not available. This expressed sequence tags (EST) analysis revealed 81 clones
      (42%) had significant homologies to known genes in GenBank. Of these clones,
      eight are related to known algal genes, whereas above 90% of the EST clones were
      newly identified in algae. Putative functional categories of these clones showed
      that the most abundant genes were involved in stress and defense mechanisms and
      that the next abundant genes were associated with protein synthetic pathways.

PMID- 10901174
TI  - Cloning, sequencing, and expression of porcine interleukin-18 in Escherichia
      coli.
AB  - IL-18 is the new name of a novel cytokine that plays an important role in T(H1)
      response, primarily by its ability to induce IFN-gamma production in T cells and
      natural killer cells. The porcine IL-18 gene was isolated using RT-PCR from
      porcine alveolar macrophages. Sequence analysis of the porcine IL-18 gene has
      demonstrated an open reading frame of 579 base pairs encoding 192 amino acids
      precursor protein with a predicted molecular mass of 22 kDa. The porcine IL-18
      gene shares 84% and 89% similarity to the human and canine equivalents,
      respectively, at the nucleotide level. The cloned IL-18 was expressed in
      Escherichia coli and its expression was confirmed by SDS-PAGE and Western
      blotting.

PMID- 10901175
TI  - A graphical tool for parametric simulation of the RNA structure formation.
AB  - It is known that RNA molecules may fold to suboptimal structures instead of
      minimum free energy structures due to the kinetics of the folding process and
      that the kinetic effect becomes more important for large RNA molecules. Thus,
      prediction of RNA structures can be improved by the study of the RNA folding
      process. This paper presents a computer program called QFolder, which simulates
      the RNA folding process in the sense of qualitative kinetics. Given a set of
      homologous RNA sequences and parameter values, QFolder predicts possible
      secondary structure motifs and folding events, which might occur during
      transcription of the RNA molecules. Each predicted structure motif is visualized
      in graphical form and its certainty factor is computed for evaluation of its
      prediction. QFolder allows a user to gain insights into the RNA folding process
      and can be used as useful aids in designing biochemical experiments to elucidate
      the RNA folding process more accurately.

PMID- 10901176
TI  - Phylogenetic analysis of retroposon family as exemplified on human chromosome 13:
      further evidence for recent proliferation.
AB  - The retroposon SINE-R.C2 was first identified as a human-specific insertion in
      the complement C2 gene. In our previous study, SINE-R type retroposons, derived
      from the endogenous retrovirus HERV-K family, have been found to be hominoid
      specific. In this report on human chromosome 13, we identified eighteen new SINE
      R retroposons resembling those we have previously reported on the sex chromosomes
      and on chromosomes 7 and 17. Phylogenetic analysis using the neighbor-joining
      method revealed that four SINE-R retroposons (13-16, 21, 23, 25) on chromosome 13
      were closely related to the human-specific retroposon SINE-R.C2, with a high
      degree of sequence homology (95-97%). Such elements differ from the HERV-K10. LTR
      sequence from which they are derived in being deleted for the promoter region.
      Therefore while the evidence adds to the case that some classes of SINE-R element
      have continued to proliferate in hominid and hominoid evolution and may, as in
      the case of Fukuyama type muscular dystrophy, be a cause of insertional
      mutagenesis, they are less likely than the HERV-K10 LTR to have a positive effect
      on host gene activity.

PMID- 10901177
TI  - Functional characterization of the rat gamma-glutamyl transpeptidase promoter
      that is expressed in transformed rat liver epithelial cells.
AB  - In the rat the gamma-glutamyl transpeptidase (GGT) gene codes for at least four
      different messenger RNAs (mRNA I to mRNA IV) which differ only in their 5'
      untranslated regions and are transcribed from a single copy gene in a tissue
      specific manner. In the liver GGT expression is up-regulated in transformed
      cells. To understand the induction mechanisms of GGT activity by transformation,
      we previously cloned the 5' region of the rat GGT gene which contains the 5'
      untranslated leader sequence for mRNA I. In the present study, using transfection
      and reporter gene assays, I have demonstrated that (1) the sequence from
      positions -369 to +226 drives a relatively strong promoter activity in C5 and AKG
      cell lines, transformed rat liver epithelial cells, but a very weak one in RLE
      228 cells, a normal rat liver epithelial cell line; and (2) removal of the region
      between -418 and -369 increases CAT activity more than 10-fold in RLE-228, C5 and
      AKG cells, and the DNA fragment spanning nucleotides -761 to -292 significantly
      reduces CAT activity driven by the adenine phosphoribosyl transferase (APRT)
      promoter in RLE-228 cells.

PMID- 10901178
TI  - Renal function and structure in diabetic, hypertensive, obese ZDFxSHHF-hybrid
      rats.
AB  - The obese ZDFxSHHF-fa/fa(cp) model was developed by crossing lean female Zucker
      Diabetic Fatty (ZDF +/fa) and lean male Spontaneously Hypertensive Heart Failure
      (SHHF/Mcc-fa(cp), +/fa) rats. The purpose of the present study was to determine
      renal function and morphology, hemodynamics, and metabolic status in ZDFxSHHF
      rats. Two sets of experiments were conducted. First, we evaluated heart and
      kidney function and metabolic status in aged (46 weeks old) male obese ZDFxSHHF
      and age matched obese SHHF rats, lean Spontaneously Hypertensive (SHR) and lean
      normotensive Wistar Kyoto (WKY) rats. In the second set of experiments, renal
      function and structure as well as metabolic and lipid status were determined in
      lean (LN) and obese (OB) adult (29-weeks of age) ZDFxSHHF rats. At 46 weeks of
      age ZDFxSHHF rats are hypertensive expressing marked cardiac hypertrophy
      associated with diastolic dysfunction and preserved contractile function. Fasted
      hyperglycemia and hyperinsulinemia are accompanied by moderate
      hypercholesterolemia and hypertriglyceridemia. Obese aged ZDFxSHHF have marked
      renal hypertrophy, a 3-8 fold decrease in creatinine clearance (compared with
      SHHF, SHR and WKY), a high percent of segmental + global glomerulosclerosis
      (59.8%+/-10.8), and severe tubulointerstitial and vascular changes. Obese
      ZDFxSHHF rats die at an early age (approximately 12 months) from end-stage renal
      failure. Studies conducted in 29-week animals showed that, although both LN and
      OB 29-week old animals are hypertensive, OB animals have more severely
      compromised renal function and structure as compared with lean litter-mates
      (kidney weight: 2.56+/-0.16 vs. 1.61+/-0.12 g; creatinine clearance: 0.42+/-0.04
      vs. 1.24+/-0.13 L/g kid/day; renal vascular resistance 12.39+/-1.4 vs. 6.14+/
      0.42 mmHg/mL/min/g kid; protein excretion: 556+/-16 vs. 159+/-9mg/day/g kid, p <
      0.05, OB vs. LN, respectively). Obesity is also associated with hyperglycemia
      (424+/-37 vs. 115+/-11 mg/dL), hyperinsulinemia (117.2+/-8.8 vs. 42.3+/-3.5
      microU/mL), hypertriglyceridemia (5200+/-702 vs. 194+/-23 mg/dL),
      hypercholesterolemia (632+/-39 vs. 109+/-4mg/dL), and presence of segmental +
      global glomerulosclerosis (20.1+/-3.2% vs. 0.1+/-0.1%) with prominent tubular and
      interstitial changes (p < 0.05, OB vs. LN, respectively). In summary, the present
      study indicates that the crossing of rat strains of nephropathy produces hybrids
      that carry a high risk for severe renal dysfunction. The ZDFxSHHF rats express
      insulin resistance, hypertension, dislipidemia and obesity and develop severe
      renal dysfunction. In addition, the hybrids do not develop some of the
      complications (hydronephrosis or congestive heart failure) common for the
      parental strains that may compromise studies of renal function and structure.
      Therefore, the ZDFxSHHF rat may be a useful model fore valuating risk factors and
      pharmacological interventions in chronic renal failure.

PMID- 10901179
TI  - Changes in expression of sodium cotransporters and aquaporin-2 during ischemia
      reperfusion injury in rabbit kidney.
AB  - Ischemic renal injury is associated with defects in transport functions of the
      proximal tubules and urinary concentration ability. To determine whether
      alterations in expression of various transporter genes contribute to an
      impairment in renal functions, the expression of various solute transport genes
      was analyzed in renal cortex and medulla of rabbits with ischemic acute renal
      failure. Rabbits were subjected to 60 min of renal pedicle clamping followed by
      24, 48, or 72 h of reperfusion. Urine volume and glomerular filtration rate were
      markedly decreased, which were accompanied by an increase in serum creatinine
      level and fraction Na+ excretion. Glucosuria and phosphaturia were evident during
      reperfusion periods. These alterations in renal functions were persisted to 72 h
      after reperfusion. The Na+-dependent uptakes of glucose and phosphate by brush
      border membrane vesicles were inhibited by 24 h of reperfusion. mRNA levels for
      Na+-glucose, Na+-phosphate, and Na+-succinate cotransporter analyzed by RT-PCR
      were not changed by 60 min of ischemia alone, but were significantly reduced by
      24 h of reperfusion. mRNA levels for apical Na+-K+-2Cl- cotransporter, NaCl
      cotransporter, and turea transporter in the medulla were not changed during
      reperfusion. Protein levels for AQP2 in the medulla, but not AQP1 in the cortex,
      analyzed by Western blot were significantly reduced at 24 h after reperfusion.
      These results suggest that reductions in expression of Na+-cotransporter genes in
      the proximal tubules may be important factors in the impairment in Na+-dependent
      reabsorption of solutes and that decrease in AQP2 protein may be involved in
      defect in urinary concentration ability in rabbits with ischemic acute renal
      failure.

PMID- 10901180
TI  - Mrna expression of transforming growth factor-alpha and the EGF receptor
      following nephrotoxic renal injury.
AB  - We studied gene expression for transforming growth factor (TGF)-alpha, epidermal
      growth factor (EGF), heparin binding (HB) EGF, and the EGF receptor following
      acute renal failure induced by mercuric chloride administration to gain insight
      into potential mechanisms of renal repair. Twenty four hours after HgCl2, 2
      mg/kg, creatinine increased from 0.3+/-0.01 mg/dl in controls to 2.2+/-0.26 mg/dl
      in injured rats (n = 5, p < 0.01). Similar changes were observed after 3 days.
      Messenger RNA expression for EGF was decreased at 24 hours in HgCl2 treated rats
      and remained depressed for at least 3 days. On the other hand steady state mRNA
      for TGF-alpha increased nearly 2 fold at day 3 in HgCl2 treated rats 4 mg/kg.
      Heparin binding EGF was increased early, by day one in injured kidneys and gene
      expression for the EGF receptor was increased as well. Immunohistochemistry
      documented an increase in expression of TGF-alpha in injured kidneys at distal
      nephron sites. These studies suggest that TGF-alpha along with HB EGF may be
      important ligands for the EGF receptor during repair from renal injury.

PMID- 10901181
TI  - Normalization of hematocrit in hemodialysis patients with cardiac disease does
      not increase blood pressure.
AB  - Since the earliest reports of the use of Epoetin alfa in hemodialysis patients,
      it has been described that Epoetin alfa may exacerbate preexisting hypertension
      or induce hypertension in End Stage Renal Disease (ESRD) patients not previously
      hypertensive. We undertook this study to determine if the correction of anemia in
      ESRD patients with cardiac disease from a hematocrit of 30+/-3% to 42+/-3% with
      the use of Epoetin alfa would result in increased blood pressure. This study was
      a substudy of the "Normal hematocrit Study". METHODS: Thirty-one patients were
      randomized into one of two arms. Patients in Group A had their hematocrit
      increased with the use of slowly escalating doses of Epoetin alfa to 42+/-3% and
      patients in Group B were maintained with a hematocrit of 30+/-3% throughout the
      course of the study. All patients had their blood pressure recorded with a 24
      hour ambulatory BP device at study entry and at 28 weeks following randomization
      when they had achieved their target hematocrit. Pre-dialysis systolic and
      diastolic BP was also recorded. RESULTS: The mean hematocrit increased in Group A
      from 29.1+/-2.4% to 40.8+/-5.2% after 30 weeks. The hematocrit in Group B
      remained stable at 30+/-3% throughout the course of the study. There was no
      difference in mean daytime, mean nighttime or 24 hour systolic or diastolic blood
      pressure between Groups A and B at either baseline or follow-up. Neither was
      there a difference in mean pre-dialysis systolic or diastolic BP between Groups A
      or B at baseline or Follow-up. Four patients in Group A and 4 patients in Group B
      required an increase in their antihypertensive medication during the course of
      the study. CONCLUSION: It is possible to increase hematocrit to normal levels in
      hemodialysis with the administration of Epoetin alfa. The increase in hematocrit
      from 30+/-3% to 42+/-3% is not associated with increased blood pressure.

PMID- 10901182
TI  - Mesangioproliferative glomerulonephritis with IgM deposition: clinical
      characteristics and outcome.
AB  - The significance of IgM on immunofluorescence in renal biopsy specimens remains
      unclear. This retrospective case study was conducted to define the clinical
      features, response to therapy and outcome of patients with Mesangioproliferative
      Glomerulonephritis (MGN) with diffuse IgM deposition. Of 1919 native renal
      biopsies performed over a ten-year period, 139 (7.2%) had light microscopic
      features of MGN and manifested IgM as the dominant immunoglobulin. When exclusion
      criteria (more than a trace of IgA or IgG, segmental IgM, evidence of SLE,
      vasculitis, FSGS or Alport's syndrome and pregnant patients) were applied, 60
      patients (3.1%) remained. Follow-up data were available for 54 cases with a mean
      age of 26.5 years (range 1.7-63). Mean follow-up period was 7.4 years (range 4.7
      22.2). Forty-one per cent presented with nephrotic syndrome (NS), 26% with
      asymptomatic proteinuria (>250mg/24hr), 18% with macroscopic hematuria and 15%
      with isolated microscopic hematuria. Twenty-one percent of patients were
      hypertensive at presentation. Creatinine was initially <120 (mol/L in all but one
      patient. Only four patients (7.4%), all nephrotic, suffered a decline in renal
      function despite treatment; all 4 developed ESRF after a mean of 5.6 years (range
      2-8.3). Two of these were subsequently re-biopsied and found to have FSGS. No
      patients with isolated microscopic / macroscopic hematuria or asymptomatic
      proteinuria suffered a decline in renal function. Protein excretion rate fell
      into the normal range in 63% of those receiving steroids, with 82% becoming
      steroid dependent. Of those treated with cyclosporine (48%) or cyclophosphamide
      (52%) only 9.5% and 14.5% respectively remained in prolonged remission after
      discontinuing treatment. It is concluded that MGN with IgM deposition carries a
      very favorable prognosis except in patients with NS who develop FSGS. However
      there is a high incidence of steroid dependence and resistance in the proteinuric
      group.

PMID- 10901183
TI  - Frequency and outcome of patients with acute renal failure have more causes than
      one in etiology.
AB  - In literature, there was little data about frequency and outcome of ARF with two
      or more causes in etiology. Therefore, the aim of this study was to search this
      issue. This series included 339 patients with ARF from Jan 1,1987 to Jan 1,1999.
      Fourty-six (30 males) of all patients (13.5%) had two or more causes in etiology
      of ARF. Of these patients, causes were prerenal and renal in 26 (56%), prerenal,
      renal and postrenal in 12 (26%), renal and postrenal in 4 (9%), and prerenal and
      postrenal in 4 (9%). The most frequent cause is diarrhea and vomiting in
      prerenal, gentamycin usage in renal and prostate hypertrophy in postrenal. Of
      these patients, there was oliguria in 32 (70%), anuria in 8 (17%) and non
      oliguria in 6 (13%). Treatment modalities of patients was only medical in 19
      (41%), dialysis in addition to medical therapy in 27 (59%). In spite of
      treatment, 5 (10.8) of patients with two or more causes in etiology died. Causes
      of death were uremic coma in 2, cardiac disorders in 2 and septic shock in 1.
      Three (11.2%) of other patients with one cause died. Mortality rates were not
      different (chi2: 0.0298, p > 0.5). Cortical necrosis was diagnosed in one patient
      with multiple etiology and 2 of other patients. Finally, frequency of ARF with
      two or more etiologic causes was 13.5%, and most frequent causes were hypovolemia
      and nephrotoxic drugs. Outcome of these patients was similar to other patients
      with one cause.

PMID- 10901184
TI  - Renal involvement in multiple myeloma: a 10-year study.
AB  - Renal involvement in 204 cases with multiple myeloma admitted over a 10-year
      period to this tertiary care center in north India was retrospectively examined.
      Renal involvement occurred in 55 cases (27%); the vast majority of whom (94.5%)
      had presented with renal failure and 7.3% had nephrotic syndrome. The diagnosis
      of multiple myeloma was made after admission in 51 of the 55 (92.7%) cases.
      Oliguria was seen in 23.6% and two-third patients required dialysis. Factors
      precipitating renal failure were identified in 53% and included dehydration
      (33%), hypercalcemia (24%), nephrotoxic drugs (16%), sepsis (9%), recent surgery
      (5%) and contrast media (2%), Severe anemia, hypercalcemia, Bence Jones
      proteinuria and skeletal abnormalities were more frequent in those with renal
      involvement. Patients with renal involvement were more likely to have a high
      tumor burden. The myeloma was of light chain type in 68% of those with renal
      involvement whereas IgG myeloma was commonest (57%) in those without evidence of
      renal disease. Renal histology was studied in 27 cases with myeloma cast
      nephropathy seen in over 60%. Tubulointerstitial nephritis was seen in 14% cases,
      11% had amyloidosis, 7% had acute tubular necrosis and 3.6% each had nodular
      glomerulosclerosis and plasma cell infiltration. In 8 cases (14.6%), renal biopsy
      provided the first clue to the diagnosis of myeloma. Renal function improved in
      33% cases. Only 22% of patients on dialysis survived over 6 months. Median
      survival in those with renal involvement was only 4 months. Development of
      unexplained renal failure in an elderly individual with normal sized kidneys, in
      association with disproportionate anemia even in the absence of skeletal lesions
      should alert the physician to the diagnosis of multiple myeloma.

PMID- 10901185
TI  - No association of glutathione S-transferase M1 gene polymorphism with diabetic
      nephropathy in Japanese type 2 diabetic patients.
AB  - Oxidative stress possibly contributes to the development of diabetic nephropathy.
      Therefore, the levels of endogenous antioxidants may be one of determinants of
      the susceptibility to diabetic nephropathy. Glutathione S-transferases (GSTs) can
      work as one of endogenous antioxidants to protect cells from oxidative stress.
      The M1 member of GST mu class (GSTM1) is polymorphic and only expressed in 55-60%
      of Caucasians because of the homozygous deletion of the gene (null genotype).
      Recent studies have provided evidence that the GSTM1 null genotype, i.e. lack of
      the GSTM1 activity, is associated with an increased susceptibility to lung cancer
      and colorectal cancer. The present study was conducted to determine whether the
      genetic polymorphism influences the development of diabetic nephropathy. We
      examined 105 patients with diabetic nephropathy and 69 patients without diabetic
      nephropathy in Japanese type 2 diabetic patients with proliferative diabetic
      retinopathy. GSTM1 genotyping was performed by polymerase chain reaction. The two
      patient groups were well matched with regard to age, body mass index and HbAlc.
      GSTM1 null genotype was observed in 48.6% of patients with nephropathy versus
      55.1% of patients without nephropathy. The frequency of GSTM1 null genotype was
      not significantly higher in the patient group with nephropathy than in the
      patient group without nephropathy. This study is the first to investigate the
      association of GSTM1 gene polymorphism with the development of diabetic
      nephropathy. The present results suggest that GSTM1 null genotype does not
      contribute to the development of diabetic nephropathy in Japanese type 2 diabetic
      patients.

PMID- 10901186
TI  - Renal function changes after elective cardiac surgery with cardiopulmonary
      bypass.
AB  - Cardiac surgery can either induce acute renal failure or improve GFR by improving
      the cardiac performance. In order to study renal function changes after elective
      cardiac surgery (CS) with cardiopulmonary bypass (CPBP), 21 patients undergoing
      valvular CS (VCS) or coronary artery bypass (CAB) were prospectively evaluated in
      three time periods: before, 24 hours after surgery and 48 hours after surgery.
      Patients were divided in 2 groups according to the GFR percent change in
      comparison to the baseline value found 24 hours after CS (deltaGFR24): Group 1,
      deltaGFR24 decrease higher than 20% (n = 11) and Group 2, deltaGFR24 decrease <
      or = 20% or deltaGFR24 increase (n = 10). In Group 1, 73% of the patients
      underwent VCS (p = 0.05 vs. Group 2) and all of them had previous VCS in sharp
      contrast with Group 2, where none of the patients had previous CS (p = 0.006).
      Patients in Group I required more volume replacement than Group 2 during the
      first 24 hours after CS: 2,699+/-704 mL versus 217+/-603 mL respectively, p =
      0.019. Despite similar baseline GFR, Group 1 presented lower GFR 24 hours after
      CS when compared to Group 2 (39+/-5 versus 75+/-8 mL/(min x 1.73m2), p = 0.001)
      and a significantly different deltaGFR 48 hours after CS as compared to Group 2 (
      21+/-11 versus +88+/-36%, p<0.01). Baseline sodium fractional excretion (FENa) in
      Group 1 was lower than in Group 2 (0.27+/-0.04 versus 0.70+/-0.12%, p = 0.01). No
      changes were observed after CS in urinary osmolality (Uosm) and urinary pH (UpH)
      in both groups. The deltaGFR24 showed positive correlation with baseline FENa (r
      = 0.44 p = 0.04) and negative correlation with volume balance during the first
      24h after CS (r = -0.63, p = 0.007). More patients in Group 1 required
      nitroprusside than in Group 2 (66% vs. 14%, p = 0.04). Anesthesia time was
      shorter in Group 1 as compared to Group 2: 323+/-21 vs. 395+/-26 min, p = 0.04.
      No significant hemolysis occurred during CS in either group. There were no
      differences in age, gender, CPBP time, need for dopamine and/or dobutamine
      between the two groups. In conclusion, patients who presented GFR decrease after
      CS underwent VCS more frequently, had more prevalence of previous CS, presented
      lower baseline FENa, required more volume infusion and more nitroprusside use. On
      the other hand, no tubular dysfunction was detected in the early follow-up of CS.
      These results suggest that the observed renal function changes should be the
      result of an appropriated renal response to a low effective blood volume. In
      fact, a low baseline FENa anticipated a GFR decrease in these patients.
      Consistently, CAB patients that usually improve their cardiac output after
      surgery showed a clear GFR improvement.

PMID- 10901187
TI  - Urinary thymidine glycol as a biomarker for oxidative stress after kidney
      transplantation.
AB  - Reactive oxygen species are generated during ischemia-reperfusion tissue injury.
      Oxidation of thymidine by hydroxyl radicals (HO*) causes formation of 5,6
      dihydroxy-5,6-dihydrothymidine (thymidine glycol). Thymidine glycol excreted in
      urine can be used as a biomarker of oxidative DNA damage. The aim of this study
      was to investigate the oxidative DNA damage in patients showing immediate
      allograft function after kidney transplantation, and to find out whether this
      damage correlates with glomerular and tubular lesions. Time dependent changes in
      urinary excretion rates of thymidine glycol, but also of total protein, albumin,
      low molecular weight (alpha1-microglobulin, beta2-microglobulin) and high
      molecular weight proteins (transferrin, IgG, alpha2-macroglobulin) were analyzed
      quantitatively and by polyacrylamide-gel electrophoresis in six patients. Urinary
      thymidine glycol was determined by a fluorimetric assay in combination with
      affinity chromatography and HPLC. After kidney transplantation the urinary
      excretion rate of thymidine glycol increased gradually reaching a maximum within
      the first 48 hours (16.56+/-11.3 nmol/m mol creatinine, ref. 4.3+/-0.97). Severe
      proteinuria with an excretion rate of up to 7.2 g/mmol creatinine was observed
      and declined within the first 24 hours of allograft function (0.35+/-0.26 g/mmol
      creatinine). The gel-electrophoretic pattern showed a nonselective glomerular and
      tubular proteinuria. The initial nonselective glomerular proteinuria disappeared
      within 48 hours, changing to a mild selective glomerular proteinuria. In this
      period (12-48 hours) higher levels of thymidine glycol excretion were observed,
      when compared to the initial posttransplant phase (13.66+/-9.76 vs. 4.31+/-3.61
      nmol/mmol creatinine; p<0.05). An increased excretion of thymidine glycol is seen
      after kidney transplantation and is explained by the ischemia-reperfusion induced
      oxidative DNA damage in the kidney. In the second phase higher levels of
      excretion were observed parallel to the change from a nonselective to a selective
      glomerular and tubular proteinuria. An explanation may be sought in the repair
      process of DNA in the glomerular and tubular epithelial cells, appearing
      simultaneously with functional recovery.

PMID- 10901188
TI  - A case with acute renal failure complicated by Waldenstrom's macroglobulinemia
      and cryoglobulinemia.
AB  - We encountered a 53-year-old man associated with acute renal failure caused by
      Waldenstrom's macroglobulinemia and type I cryoglobulinemia. Treatment with
      prednisolone and cyclophosphamide induced a rapid recovery from acute renal
      failure. Renal histology revealed endocapillary proliferation and lobular
      formation with scattered subendothelial, amorphous and periodic acid-Schiff (PAS)
      positive materials in the glomerular capillaries which were positive for IgM on
      immunofluorescence study. Although the exact mechanism for pathophysiology of
      acute renal failure remains unknown, treatment with prednisolone and
      cyclophosphamide could induce a rapid recovery from acute renal failure
      accompanied by Waldenstrom's macroglobulinemia and type I cryoglobulinemia.

PMID- 10901189
TI  - Systemic lupus erythematosus presenting initially as hydrogen ATPase pump defects
      of distal renal tubular acidosis.
AB  - Tubulointerstitial involvement is well recognized in systemic lupus
      erythematosus. The tubular dysfunction is usually latent and usually presents
      after diagnosis of systemic lupus erythematosus. We report a case presenting that
      she is well previously and initially diagnosed as periodic paralysis of
      hypokalemia at emergency room and final diagnosis is systemic lupus erythematosus
      with H+-ATPase pump defect of distal type renal tubular acidosis. Kidney biopsy
      showed lupus nephritis classified as mesangial proliferative glomerulonephritis
      WHO class II B. Her renal tubular acidosis was subsided after steroid therapy was
      administered.

PMID- 10901190
TI  - Effects of selection for increased body weight, egg production, and shank width
      on developmental stability in turkeys.
AB  - Bilateral asymmetry was measured at 20 wk of age for shank length, shank width
      (width laterally at the dew claw), shank depth (width perpendicular to the dew
      claw), and face length (between auditory canal opening and the posterior junction
      of the upper and lower mandible) in three randombred control lines and three
      selected lines of turkeys. The data were based on 50 or 51 individuals per line
      and sex subgroup from a single hatch. The lines were grown intermingled with the
      sexes being grown in different houses. The selected lines had been selected for
      increased egg production (38 generations), increased 16-wk BW (32 generations),
      or increased shank width (19 generations) and had a higher level of inbreeding
      (average = 36.9%) than the randombred controls (RBC; average = 11.6%). The
      bilateral differences (right minus left) were analyzed for the presence of
      fluctuating asymmetry (FA; zero signed mean with normal variation), directional
      asymmetry (DA; signed mean not zero with normal variation), and antisymmetry (AS;
      zero mean with non-normal distribution). In order to adjust for possible scaling
      effects, relative asymmetry (RA), in which the mean of the absolute differences
      between sides was divided by the mean of the two sides and the resulting value
      was multiplied by 100, was used as a measure of bilateral asymmetry. The
      randombred control and selected lines were contrasted to study the effect of
      homozygosity on RA. Likewise, the large-bodied lines (F, FL, and RBC3) were
      contrasted to the small-bodied lines (RBC1, E, and RBC2) to study the effect of
      BW on RA. Only two types (FA and DA) of asymmetry were observed in the present
      study. The level of asymmetry for the traits was ranked as follows: face length >
      shank width = shank depth > shank length. The individual lines differed in RA for
      shank length and shank width for both sexes and for shank depth and face length
      in females. In general, the influence of BW, as measured in the contrast of large
      bodied and small-bodied lines, on RA was larger than that of homozygosity, as
      measured by the contrast of the selected and randombred control lines.

PMID- 10901191
TI  - Research notes: passive integrated transponder tags as markers for chicks.
AB  - Passive integrated transponder (PIT) tags have been used to mark a variety of
      organisms and have potential for marking poultry chicks. We examined the effects
      of PIT tags subcutaneously implanted in 3- and 7-d-old Leghorn chicks and found
      no significant differences over 40 d in survival or rate of daily body mass gain
      among tagged chicks and controls. The PIT-tagged birds were not more susceptible
      to pecking by other chicks than controls. No birds died, but 1 of 20 chicks lost
      its tag during the study. We believe that PIT tags provide a viable technique for
      marking individual juvenile birds, if tag loss can be reduced. Costs may be
      prohibitive in studies involving large numbers of birds.

PMID- 10901192
TI  - Immunomodulatory effects of indomethacin and prostaglandin E2 on primary and
      secondary antibody response in growing layer hens.
AB  - Effects of prostaglandin E2 (PGE2) and indomethacin, an inhibitor of PGE2
      oxygenase, on primary and secondary antibody (Ab) responses to Mycobacterium
      butyricum protein or keyhole limpet hemocyanin (KLH) were studied in growing
      layer hens. Immunizations at 35 and 70 d of age were accompanied by
      immunomodulating treatments with PGE2, indomethacin, or PBS. In addition, we
      studied effects of various doses of indomethacin and PGE2 on mitogen-induced T
      cell proliferation in vitro. Secondary Ab responses to KLH were enhanced by
      administration of indomethacin at secondary immunization and, to a lesser extent,
      by PGE2 administration at secondary immunization. Primary Ab responses to M.
      butyricum tended to decrease by administration of either PGE2 or indomethacin.
      Secondary Ab responses to M. butyricum were affected by administration of both
      PGE2 and indomethacin at primary immunization. Prostaglandin E2 increased
      phytohemagglutinin (PHA)-induced lymphocyte proliferation. Indomethacin decreased
      Concanavalin A (ConA)- and PHA-induced lymphocyte proliferation. The net effect
      of indomethacin on the Ab response could not be explained by inhibition of PGE2
      oxygenase only. Our data rather suggest an inhibition by indomethacin of other
      immunosuppressing factors derived from arachidonic acid. We concluded that
      polyunsaturated fatty acid-derived products might especially affect secondary
      antibody responsiveness. This finding may depend on inhibition or enhancement of
      T-cell responsiveness. Consequently, immunomodulation by dietary polyunsaturated
      fatty acids may have profound effects at secondary rather than at primary
      exposure to pathogens.

PMID- 10901193
TI  - Effect of dietary lipase enzyme on gut morphology, gastric motility, and long
      term performance of broiler chicks.
AB  - Three experiments were conducted to test a previously described anorexic effect
      of graded dietary supplements of Pancreatic lipase enzyme on gut structure,
      gastric motility, and long-term performance of broiler chicks. In Experiment 1,
      dietary Pancreatic enzyme was used at graded levels of 0, 0.214, 0.429, 0.643,
      0.857, and 1.071% to test the effect of this enzyme on gut structure, whereas
      Experiment 2 was designed to test its effect at 0, 0.268, 0.536, 0.804, 1.071,
      and 1.339% on gastric motility. The histological examination of the small
      intestine and a cineradiographic study of birds fed diets supplemented with
      lipase enzyme failed to detect any difference in gut structure, and there was no
      apparent adverse effect on gastric motility. Experiment 3 was conducted to test
      the effect of graded supplements of Pancreatic enzyme on performance of 300 male
      broiler chicks raised for 6 wk to determine whether the enzyme had any long-term
      effect on performance characteristics, especially feed intake. Only starter diets
      (0 to 21 d) were supplemented with 0, 0.375, 0.750, or 1.125% enzyme, and each
      diet was represented by three replicate pens of 25 male chicks each. Subsequent
      diets did not contain any enzyme. During the first 3 wk, increased dietary
      concentration of lipase enzyme caused a linear reduction of feed intake and body
      weight gain (P < 0.01). At 21 d the percentage weight of the liver was
      significantly greater with 1.125% enzyme (P < 0.01). However, added enzyme had no
      effect on 21 to 42 d or 1 to 42 d growth or feed intake (P > 0.05) or on the size
      of any internal organs examined at 42 d. Pancreatic enzyme has previously been
      shown to improve fat digestion and increase diet AMEn for young chicks fed animal
      vegetable blended fats. These positive effects, however, are associated with
      marked anorexia, and from the present study, it seems that this effect was not
      related to physical changes in gut histology or in prolonged digesta transit
      time.

PMID- 10901194
TI  - Human requirement for N-3 polyunsaturated fatty acids.
AB  - The diet of our ancestors was less dense in calories, being higher in fiber, rich
      in fruits, vegetables, lean meat, and fish. As a result, the diet was lower in
      total fat and saturated fat, but contained equal amounts of n-6 and n-3 essential
      fatty acids. Linoleic acid (LA) is the major n-6 fatty acid, and alpha-linolenic
      acid (ALA) is the major n-3 fatty acid. In the body, LA is metabolized to
      arachidonic acid (AA), and ALA is metabolized to eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA). The ratio of n-6 to n-3 essential fatty acids was 1
      to 2:1 with higher levels of the longer-chain polyunsaturated fatty acids (PUFA),
      such as EPA, DHA, and AA, than today's diet. Today this ratio is about 10 to 1:20
      to 25 to 1, indicating that Western diets are deficient in n-3 fatty acids
      compared with the diet on which humans evolved and their genetic patterns were
      established. The n-3 and n-6 EPA are not interconvertible in the human body and
      are important components of practically all cell membranes. The N-6 and n-3 fatty
      acids influence eicosanoid metabolism, gene expression, and intercellular cell-to
      cell communication. The PUFA composition of cell membranes is, to a great extent,
      dependent on dietary intake. Therefore, appropriate amounts of dietary n-6 and n
      3 fatty acids need to be considered in making dietary recommendations. These two
      classes of PUFA should be distinguished because they are metabolically and
      functionally distinct and have opposing physiological functions; their balance is
      important for homeostasis and normal development. Studies with nonhuman primates
      and human newborns indicate that DHA is essential for the normal functional
      development of the retina and brain, particularly in premature infants. A
      balanced n-6/n-3 ratio in the diet is essential for normal growth and development
      and should lead to decreases in cardiovascular disease and other chronic diseases
      and improve mental health. Although a recommended dietary allowance for essential
      fatty acids does not exist, an adequate intake (AI) has been estimated for n-6
      and n-3 essential fatty acids by an international scientific working group. For
      Western societies, it will be necessary to decrease the intake of n-6 fatty acids
      and increase the intake of n-3 fatty acids. The food industry is already taking
      steps to return n-3 essential fatty acids to the food supply by enriching various
      foods with n-3 fatty acids. To obtain the recommended AI, it will be necessary to
      consider the issues involved in enriching the food supply with n-3 PUFA in terms
      of dosage, safety, and sources of n-3 fatty acids.

PMID- 10901195
TI  - Enriched eggs as a source of N-3 polyunsaturated fatty acids for humans.
AB  - Dietary intake of omega-3 fatty acids (n-3 PUFA) decreases the risk of heart
      disease, inhibits the growth of prostate and breast cancer, delays the loss of
      immunological functions, and is required for normal fetal brain and visual
      development. The US has not established a recommended daily intake for n-3 PUFA.
      However, Canada has established the Canadian Recommended Nutrient Intake (CRNI)
      at 0.5% of energy. Dietary sources of n-3 PUFA include fish, chicken, eggs,
      canola oil, and soybean oil. Food consumption studies in the US indicate that the
      majority of Americans do not meet the CRNI for n-3 PUFA. Mean n-3 PUFA
      consumption was 78% of the CRNI for Midwestern women during pregnancy. In
      Midwestern women at risk for breast cancer, the mean n-3 PUFA consumption is
      approximately 50% of the CRNI. Increased consumption of n-3 PUFA requires
      identification of a food source that the public would eat in sufficient amounts
      to meet recommended intake. N-3 PUFA-enriched eggs can be produced by modifying
      hens diets. When 70 g/kg of cod liver oil, canola oil, or linseed oil are added
      to a commercial control diet, the n-3 PUFA are increased from 1.2% of egg yolk
      fatty acids to 6.3, 4.6, and 7.8%, respectively. Feeding flaxseed increases
      linolenic acid in the egg yolk about 30-fold, and docosahexaenoic acid (DHA)
      increases nearly fourfold. When individuals are fed four n-3 PUFA-enriched eggs a
      day for 4 wk, plasma total cholesterol levels and low-density lipoprotein
      cholesterol (LDL-C) do not increase significantly. Plasma triglycerides (TG) are
      decreased by addition of n-3 PUFA-enriched eggs to the diet. N-3 PUFA may
      influence LDL particle size, causing a shift toward a less atherogenic particle.
      Blood platelet aggregation is significantly decreased in participants consuming n
      3 PUFA-enriched eggs. Overall results of studies to date demonstrate positive
      effects and no negative effects from consumption of n-3-enriched eggs. Three n-3
      PUFA-enriched eggs provide approximately the same amount of n-3 PUFA as one meal
      with fish. It is recommended that n-3 PUFA-enriched eggs be used as one source of
      n-3 PUFA to increase individual consumption to meet the current Canadian
      recommendations.

PMID- 10901196
TI  - Producing and marketing a specialty egg.
AB  - Eggland's Best, Inc. markets premium quality shell eggs under the Eggland's Best
      (EB) brand name. The company, started in 1988, is comprised of a franchise
      network of established egg producers and covers most of the United States.
      Eggland's Best provides its franchisees with marketing and technical support. The
      franchisees produce, process, and distribute EB eggs according to the strict
      program established and monitored by EB. Production follows the all-natural
      vegetarian feed program in accordance with the company's US patent entitled "Eggs
      Compatible with a Cholesterol Reducing Diet and Method of Producing the Same."
      The EB program excludes animal fat and other animal byproducts. Eggland's Best
      eggs have seven times the generic level of vitamin E, nearly three times more
      omega-3 fatty acids and iodine, and 25% less saturated fat than regular generic
      eggs. Eggland's Best has one of the finest shell egg quality assurance programs
      anywhere. Eggland's Best franchisees submit weekly egg samples that are analyzed
      for shell quality, interior quality, vitamin E, iodine, cholesterol and fatty
      acids. Samples of feed and the EB-patented feed supplement are also analyzed.
      Approximately 28,000 total laboratory tests are conducted annually. Nationwide
      product and display retail evaluations are contracted through an outside audit
      company (40 to 50 cities evaluated four times per year). All EB eggs are USDA
      graded according to EB's strict quality standards. Producers must follow a food
      safety quality assurance program (United Egg Producers Association 5-Star or
      equivalent state or company program). Each egg is stamped "EB" as assurance of
      meeting EB's highest standards of flavor, quality, and nutrition. Eggland's Best
      has enjoyed record sales growth for the past 3 yr.

PMID- 10901197
TI  - Initiation and promotion of endochrondral bone formation by bone morphogenetic
      proteins: potential implications for avian tibial dyschondroplasia.
AB  - The initiation and promotion of bone morphogenesis is regulated by bone
      morphogenetic proteins. Morphogenesis of the skeleton is the developmental
      cascade of pattern formation, establishment of mirror-image bilateral symmetry,
      initiation and promotion of endochondral bone differentiation, and growth
      culminating in functional weight bearing. Implantation of demineralized bone
      matrix initiates a developmental cascade of endochondral bone formation that is
      reminiscent of the sequential bone morphogenesis in the limb bud in the embryo.
      The inductive agents in the demineralized bone matrix were identified, isolated
      and cloned, and demonstrated to be bone morphogenetic proteins (BMP). The BMP
      have been implicated in the pattern formation, differentiation, and regeneration
      of bone. Because there is a persistent defect in endochondral bone formation in
      the epiphysed growth plate in tibial dyschondroplasia in poultry, it is likely
      that BMP signaling mechanisms may be impaired.

PMID- 10901198
TI  - Skeletal deformities and their causes: introduction.
AB  - Much has been done to characterize skeletal deformities in poultry and to
      identify the causes of these deformities. However, skeletal problems in poultry
      continue to cost poultry producers over $100 million per year. A basic
      understanding of bone growth and development is essential for continuous progress
      in solving current skeletal diseases. Although this research will be of great
      benefit to the poultry industry, the use of poultry models has proven valuable in
      studying human bone disease.

PMID- 10901199
TI  - The role of the extracellular matrix in skeletal development.
AB  - The extracellular matrix of cartilage and bone is composed mostly of collagen
      with lesser amounts of other constituents such as proteoglycans. The focus of
      this brief review will be on the dynamic expression of collagens and
      proteoglycans in the cartilage and bone extracellular matrices. Recent research
      has shown the presence of different collagen types and proteoglycans that are
      differentially expressed in cartilage, in the transition from cartilage to bone,
      and in the bone extracellular matrices. These findings suggest the complexity of
      the skeletal extracellular matrix as well as its dynamic expression. Although the
      composition of both the cartilage and bone extracellular matrices are largely
      known, the function of each of the macromolecules composing these matrices and
      their developmental regulation is not well understood. Defects that modify the
      extracellular matrix, like the chicken chondrodysplasia, nanomelia, and tibial
      dyschondroplasia, have profound affects on skeletal structure. The poultry
      industry is currently confronting a high percentage of skeletal deformities due
      to selection for increased growth rate and needs to consider the effect of
      extracellular matrix modifications and how to maintain extracellular matrix
      integrity.

PMID- 10901200
TI  - Cartilage turnover in embryonic chick tibial explant cultures.
AB  - Growth plate cartilage regulates the rate of growth and ultimate length of
      several bones in the skeleton. Chondrocytes within the growth plate proliferate,
      differentiate, enlarge, and die. The extracellular matrix undergoes synthesis,
      reorganization, and eventually degradation. The majority of research in growth
      plate physiology has focused on the proliferation and differentiation of
      chondrocytes as well as proteins they produce for the extracellular matrix.
      However, little is known about the transition from hypertrophic to apoptotic
      chondrocytes or the regulation of terminal degradation of cartilage prior to bone
      formation. An explant culture has been developed to study cartilage
      differentiation using 12-d-old embryonic chick tibiae. We have modified the
      explant culture and are using it to further elucidate mechanisms involved in the
      regulation of growth plate cartilage turnover. In our cultures, chondrocytes
      mature and then die, completely degrading the cartilage in approximately 16 d.
      The matrix undergoes a predictable pattern of degradation in which proteoglycans
      followed by collagen are removed. Increases in matrix metalloproteinase activity
      and nitric oxide production are detected in cartilage concurrently with release
      of proteoglycans into media. Inhibitors of nitric oxide inhibit nitric oxide
      production and proteoglycan degradation, suggesting that nitric oxide, at least
      in part, regulates growth plate cartilage turnover in the explant culture.
      Information gained from using this explant culture will aid in understanding the
      regulation of growth plate cartilage turnover in vivo and potentially help
      determine the cause of bone growth diseases such as tibial dyschondroplasia.

PMID- 10901201
TI  - Chondrocytes and longitudinal bone growth: the development of tibial
      dyschondroplasia.
AB  - Growth plate cartilage is central to the process of bone elongation. Chondrocytes
      originating within the resting zone of the growth plate proceed through a series
      of intermediate phenotypes: proliferating, prehypertrophic and hypertrophic,
      before reaching a terminally differentiated state. Disruption of this chondrocyte
      maturational sequence causes many skeletal abnormalities in poultry such as
      tibial dyschondroplasia (TD), which is a common cause of deformity and lameness
      in the broiler chicken. Cell and matrix components of the growth plate have been
      studied in order to determine the cause(s) of the premature arrest of chondrocyte
      differentiation and retention of prehypertrophic chondrocytes observed in TD.
      Chondrocyte proliferation proceeds normally in TD, but markers of the
      differentiated phenotype, local growth factors, and the vitamin D receptor are
      abnormally expressed within the prehypertrophic chondrocytes above, and within,
      the lesion. Tibial dyschondroplasia is also associated with a reduced incidence
      of apoptosis, suggesting that the lesion contains an accumulation of immature
      cells that have outlived their normal life span. Immunolocalization studies of
      matrix components suggest an abnormal distribution within the TD growth plate
      that is consistent with a failure of the chondrocytes to fully hypertrophy. In
      addition, the collagen matrix of the TD lesion is highly crosslinked, which may
      make the formed lesion more impervious to vascular invasion and osteoclastic
      resorption. Recent studies have applied the techniques of differential display
      and semiquantitative reverse transcriptase-polymerase chain reaction to RNA
      obtained from discrete populations of growth plate chondrocytes of different
      maturational phenotypes. This strategy has allowed us to compare phenotypically
      identical cell fractions from normal and TD growth plates in an attempt to
      identify possible candidate genes for TD.

PMID- 10901202
TI  - Perspectives on osteoblast and osteoclast function.
AB  - We present evidence that the polar, matrix-forming osteoblasts are connected
      laterally to form an impervious layer of cells. Next, the possible mechanisms by
      which calcium ions are translocated across the layer of cells into sites of
      mineralization are analyzed. Finally, mechanisms of attachment of bone-resorbing
      osteoclasts are considered. Osteoclasts adhere to matrix, in part, though an
      arginine-glycine-aspartic acid (RGD)-dependent mechanism. Adherence is under
      control of parathyroid hormone and 17beta-estradiol.

PMID- 10901203
TI  - Gene expression and tibial dyschondroplasia.
AB  - Tibial dyschondroplasia (TD) is a skeletal deformity associated with rapid growth
      in a number of avian species. The disease is the result of a disruption in the
      cascade of events that occur in the epiphyseal growth plate. Whereas the
      incidence of TD is susceptible to genetic selection, no specific genetic defect
      has been identified. Although there are extensive data describing the
      morphological and biochemical characteristics of the lesion, the mechanism of
      lesion formation is unknown. However, naturally occurring or induced genetic
      mutations in other species can provide important clues to possible mechanisms
      responsible for lesion development. Disruption of normal chondrocyte
      differentiation by constitutive activation of the parathyroid hormone/parathyroid
      hormone-related peptide (PTH/PTHrP) receptor, inactivation of the fibroblast
      growth factor receptor-3 (FGFR-3) receptor, and blocking vascular endothelial
      growth factor (VEGF) signaling all result in lesions that resemble TD. Impairment
      of vascular penetration due to the ablation of matrix metalloproteinase-9 (MMP-9)
      or tartrate-resistant acid phosphatase (TRAP) activity also results in similar
      cartilage abnormalities. We have integrated these observations with our current
      knowledge of TD to describe a hypothesis for the sequence of events responsible
      for the development of tibial dyschondroplastic lesions.

PMID- 10901204
TI  - New insight in eggshell formation.
AB  - The matrix proteins that participate in crystalization fulfill important
      functions during the formation of the calcified tissues and contribute to the
      biomechanical properties of the mature product. We suggest that osteopontin (OPN)
      is part of an array of macromolecules synthesized and secreted by the cells
      adjacent to the mineralization front that self-assemble outside the cell and
      direct crystal formation. The OPN meets the theoretical requirements for
      involvement in the mineralization process. The phosphorylated residues of acidic
      phosphoprotein have been shown to exist in the protein as reactive monoesters
      that are available for interaction with other ions, among them crystal
      constituents such as calcium ions. In addition, sulfation of OPN was also found
      to be associated with mineralization of other tissues. In contrast to the
      calbindin gene, whose expression is dependent on the calcium flux, the regulation
      of OPN synthesis is at least in part dependent on the mechanical strain imposed
      by the resident egg. These results demonstrate the complexity of the regulation
      of the matrix genes governing eggshell formation.

PMID- 10901205
TI  - Nutrition and skeletal problems in poultry.
AB  - Several excellent reviews regarding nutrition and skeletal disorders have
      appeared in the last 20 yr. This review will cover several areas of vitamin D
      research, the area of feed deprivation, and bone abnormalities, because there has
      been considerable interest in these areas during the past 10 yr. Studies indicate
      that the quantitative requirement for cholecalciferol (D3) for broiler chickens
      is much greater than previously thought. Ascorbic acid may play a role in
      stimulating 1-hydroxylation of 25-hydroxycholecalciferol [25-(OH)D3], but the
      evidence is not clear under exactly what conditions this relationship is
      important in practical prevention of tibial dyschondroplasia. Studies indicate
      that dietary supplementation with 1,25-dihydroxycholecalciferol [1,25(OH)2D3]
      will reduce the incidence of tibial dyschondroplasia in three different strains
      of broilers bred to develop a high incidence of the disease. But it did not
      prevent the disease totally in the strains, unless high enough levels of 1,25
      (OH)2D3 were fed to reduce growth rate. These studies indicate that these high
      tibial dyschondroplasia strains have a defect(s) in vitamin D metabolism. Studies
      continue to elucidate the role of ultraviolet light in preventing leg
      abnormalities. Only a few studies have been conducted on the efficacy of various
      vitamin D3 derivatives to prevent tibial dyschondroplasia. Feed deprivation
      continues to be an intriguing method of preventing tibial dyschondroplasia, and
      examination of exactly how this prevents the bone abnormality could open avenues
      for explaining the disease.

PMID- 10901206
TI  - Factors regulating bone maturity and strength in poultry.
AB  - Adolescent meat-type poultry and cage layers exhibit a high incidence of bone
      problems that include bone weakness, deformity, breakage, and infection and
      osteoporosis-related mortalities. These problems include economic and welfare
      issues. To improve bone quality in poultry, it is essential to understand the
      physiological basis of bone maturity and strength in poultry. A complex array of
      factors that include structural, architectural, compositional, physiological, and
      nutritional factors interactively determine bone quality and strength. Bone is
      approximately 70% mineral, 20% organic, and 10% water. Collagen is the major
      organic matrix that confers tensile strength to the bone, whereas hydroxyapatite
      provides compressional strength. In recent years, the roles of different collagen
      crosslinks have been shown to be important in the increase of bone mechanical
      strength. Similarly, age-related glyco-oxidative modifications of collagen have
      been shown to increase the stiffness of collagen. These posttranslational
      modifications of matrix can affect bone quality as it would be affected by the
      changes in the mineralization process. Our studies show that the growth in the
      tibia continued until 25 wk of age, which correlated with the increase in the
      content of hydroxylysylpridinoline (HP) and lysylpyridinoline (LP), the collagen
      crosslinks. The tibia from 5-wk-old chicks were strong but brittle because of low
      collagen crosslinks and high mineral content. Bone maturity may relate to its
      crosslink content. Compared to crosslink content, bone density and ash content
      showed moderate increases during growth. The bones from younger turkeys were more
      susceptible to corticosteroid-induced stunting of growth, which also resulted in
      decreased bone strength. This review discusses how different factors can
      compromise bone strength by reducing growth, altering shape, affecting
      mineralization, and affecting collagen crosslinking.

PMID- 10901207
TI  - Osteoporosis in cage layers.
AB  - Osteoporosis in laying hens is a condition that involves the progressive loss of
      structural bone during the laying period. This bone loss results in increased
      bone fragility and susceptibility to fracture, with fracture incidences of up to
      30% over the laying period and depopulation not uncommon under commercial
      conditions. A major cause of osteoporosis is the switch in bone formation from
      structural to medullary bone at the onset of sexual maturity, but structural bone
      loss is accelerated by the relative inactivity of-caged birds. Allowing birds
      more exercise, as in aviary systems, results in better bone quality but may not
      decrease the overall fracture incidence. Good nutrition can help to minimize
      osteoporosis but is unable to prevent it. Best nutritional practice involves
      transferring birds to a higher calcium diet at lighting up rather than at first
      egg, providing a source of calcium in particulate form, and not withdrawing feed
      some days before depopulation. Breeding may be an effective way of combating
      ostoporosis. Some bone strength traits have been shown to be heritable, and
      divergent selection for resistance or susceptibility to osteoporosis has resulted
      in lines with markedly different bone characteristics. After three generations of
      selection, the lines differ by 19% for keel bone mineral density, 13% for humerus
      breaking strength, and 25% for tibia breaking strength and show a sixfold
      difference in fracture incidence under commercial breeding conditions. The
      difference in bone quality among the lines is maintained under different housing
      systems.

PMID- 10901208
TI  - Molecular pathogenesis of staphylcoccal osteomyelitis.
AB  - Staphylococcus aureus is the most prominent musculoskeletal pathogen of man and
      animals. The persistent emergence of antibiotic-resistant strains has prompted
      renewed efforts to develop alternative protocols for the treatment and prevention
      of staphylococcal disease. These efforts have included attempts to develop an
      effective staphylococcal vaccine. Among the potential vaccine candidates are a
      group of surface proteins that act as adhesins by virtue of their ability to bind
      host proteins present in plasma and in the extracellular matrix. Because of our
      interest in the treatment and prevention of musculoskeletal infection, we have
      focused on adhesins that contribute to the colonization of bone and cartilage.
      Based on reports suggesting that colonization is a conserved characteristic of S.
      aureus strains that cause osteomyelitis and septic arthritis, we have paid
      particular attention to the factors that contribute to the ability to bind
      collagen. To date, only one collagen-binding adhesin (Cna) has been identified,
      and the gene encoding this adhesin (cna) is not present in most S. aureus
      strains. The possibility that a rare phenotype is conserved among isolates that
      cause a particular form of infection suggests a cause-and-effect relationship in
      which the phenotype contributes to the pathogenesis of the disease. To further
      evaluate that hypothesis, we attempted to determine whether Cna is the only
      collagen-binding adhesin produced by S. aureus and whether strains that encode
      cna share additional characteristics that distinguish them from other S. aureus
      strains. We also studied whether immunization with Cna induces a protective
      immune response. Our results confirm that Cna is the primary and probably the
      only collagen-binding adhesin and that the genetic element encoding cna does not
      encode any additional virulence factors. These results strongly suggest that the
      only consistent difference between cna-positive and cna-negative strains is the
      ability to bind collagen. We also demonstrated that vaccination with a
      recombinant fragment of Cna can protect animals against septic death and limit
      the ability to colonize bone.

PMID- 10901209
TI  - Turkey osteomyelitis complex.
AB  - Turkey osteomyelitis complex (TOC) is defined by the US Food Safety Inspection
      Service (FSIS) to include normal-appearing processed turkey carcasses that
      contain lesions including green discoloration of the liver, arthritis/synovitis,
      soft-tissue abscesses, and osteomyelitis of the proximal tibia. The lesions are
      associated with many different opportunistic organisms, mainly Staphylococcus
      aureus and Escherichia coli, suggesting that TOC incidence may be influenced more
      by deficiencies in the host immune response rather than by the virulence of any
      one organism. This syndrome is primarily a disease of adolescent male turkeys,
      and birds with TOC lesions have decreased indices of cell-mediated immunity,
      leading to the hypothesis that defects in the immune response of individuals
      within flocks of male turkeys may be responsible for the occurrence of these
      opportunistic infections. We have developed an experimental model for this
      disease in which treatment with dexamethasone (DEX), either with or without air
      sac inoculation with Escherichia coli, produces all of the lesions associated
      with TOC. These studies suggest that TOC is a result of stress-induced
      immunosuppression in a subpopulation of male turkeys that respond to the
      stressors in modern poultry production in a detrimental manner. Supplemental
      vitamin D3 treatment protected male turkeys from the immunosuppression induced by
      multiple treatments with DEX and resulted in decreased incidence of mortality,
      TOC, green liver, and isolation of bacteria from tissues, lower air sacculitis
      scores, and lower heterophil to lymphocyte ratios than nonsupplemented controls.
      Vitamin D3 also protected BW; relative weights of the liver, heart, spleen, and
      bursa; and clinical chemistry values from the effects of DEX treatment. The
      ability of vitamin D3 supplementation to protect turkeys from the
      immunosuppressive effects of severe stress emphasizes its role as a prohormone
      that affects health and disease resistance in turkeys and suggests that variation
      in the vitamin D receptor genotype may be involved in this disease process. This
      model has potential value in the identification of other nutritional and
      physiological immunomodulators that can decrease TOC incidence and will provide a
      means for the divergent selection of birds more resistant to the stressors of
      turkey production. In addition, this model will provide justification for
      management options designed to minimize stress.

PMID- 10901210
TI  - Characteristics of pale, soft, exudative broiler breast meat.
AB  - The objective of the study was to characterize pale breast meat, compare it with
      normal colored breast meat, and determine whether it should be considered pale,
      soft, and exudative (PSE). Characteristics of 20 normal and 20 pale broiler
      breasts, obtained at a commercial slaughter plant, were evaluated. Compared with
      normal meat, the pale breast meat had a significantly (P < 0.05) lower pH (5.7
      vs. 5.9), higher color L* value (60.0 vs. 55.1), higher drip loss (1.34 vs.
      0.87%), lower marinade uptake (31.2 vs. 44.3%), and lower cooking yields (95.2
      vs. 105.8%). Protein solubility in pale samples was slightly (P < 0.05) lower
      than in normal samples, which suggests increased protein denaturation in the pale
      breasts. Correlations between pH and L* value (r = -0.76), pH and marinade uptake
      (r = 0.64), sarcoplasmic protein solubility and L* value (r = -0.71), and
      sarcoplasmic protein solubility and moisture uptake (r = 0.66) and cooking yield
      (r = 0.66) were significant (P < 0.05). Correlations between total protein
      solubility and moisture uptake or cooking yields were not significant. The low
      ultimate pH of pale breast muscle appears to be the main determinant of its low
      water-holding capacity (WHC). This lower pH was unrelated to a higher lactate
      concentration or glycolytic potential of the pale muscle. Further research is
      needed to determine the causes of the low pH and possible measures to increase
      the pH (and functionality) of pale broiler breast muscle. Because the pale breast
      muscle has a low WHC, it can be considered PSE.

PMID- 10901211
TI  - Electrical stunning and exsanguination decrease the extracellular volume in the
      broiler brain as studied with brain impendance recordings.
AB  - Electrical stunning in the process of slaughtering poultry is used to induce
      unconsciousness and immobilize the animal for easier processing. Unconsciousness
      is a function of brain damage. Brain damage has been studied with brain impedance
      recordings under ischemic conditions. This experiment studies brain impedance as
      a response to a general epileptiform insult caused by electrical stunning and
      ischemia caused by exsanguination. Brain impedance was recorded in 10 broiler
      chickens for each of three killing methods: whole body electrical stunning, which
      induces cardiac arrest; head only electrical stunning followed by exsanguination;
      and exsanguination without stunning. Brain impedance was converted into relative
      extracellular volume (ECV) values. Results showed that, immediately after
      electrical stunning, the ECV decreased 5.5% from base ECV. With exsanguination
      only, the ECV decreased from base ECV only after 4 min after neck cutting. The
      ECV decrease after 10 min did not differ between treatments. With a time of 228 s
      to reach one-half of the ECV decrease found at 10 min, electrical stunning
      resulted in a much faster change in ECV than exsanguination only (373 s). Within
      the head only stunning group, six animals showed a response similar to that found
      with whole body stunning; the other four animals responded similarly to the
      animals that were exsanguinated only. It was concluded that brain impedance
      recordings used with electrical stunning reflect brain damage. This damage was
      both epileptic and ischemic in nature. Whole body stunning induced immediate
      brain damage, suggesting that an adequate stun was delivered. The dual response
      found with head only stunning might indicate that this stunning method does not
      always produce an adequate stun.

PMID- 10901212
TI  - The influence of rapid air cooling and carbon dioxided cooling and subsequent
      storage in air and carbon dioxide on shell egg quality.
AB  - This study examined the effect of rapid cooling with air and CO2 on shell egg
      quality over 14 wk. The 240 fresh eggs were initially heated to 47 C for 24 h in
      an incubator, cooled using rapid air cooling or CO2 cooling, and then stored in
      air or CO2 in 250-mL jars for 14 wk. The CO2 levels were recorded of the jar
      atmosphere, of the egg air cell, and of the egg albumen. The Haugh units of each
      egg, pH, and of albumen from five eggs per group were also recorded. Haugh units
      are a logarithmic, empirical relationship between albumen height and egg weight
      (Stadelman, 1995). Haugh units for the control eggs averaged 70.8 over 10 wk of
      the study. The control eggs were of such poor quality that they could not be
      sampled after 10 wk. The air-cooled and CO2-stored eggs averaged 70.3 Haugh units
      over the 14-wk storage period; however, the egg quality significantly
      deteriorated after 10 wk. The CO2-cooled and CO2-stored eggs averaged 75.9 Haugh
      units over the 14 wk study, with no observable decrease in quality. Rapid air
      cooling produces a lower quality egg than rapid cooling with CO2. Subsequent
      storage of rapidly air-cooled eggs in C02 may increase shelf life, but Haugh
      units were not statistically different from rapid air-cooled eggs. CO2-cooling
      and subsequent storage in CO2 increased Haugh units. The shelf life of shell eggs
      could be extended to greater than 14 wk when the eggs were CO2-cooled and CO2
      stored.

PMID- 10901213
TI  - Hunting bill promised as Burns report is published.

PMID- 10901214
TI  - Pulmonary pathology of harbour porpoises (Phocoena phocoena) stranded in England
      and Wales between 1990 and 1996.
AB  - The pathological changes observed in the lungs of 197 freshly dead to moderately
      decomposed harbour porpoises (Phocoenaphocoena) stranded in England and Wales
      between October 1990 and December 1996 were reviewed. In 135 (69 per cent of the
      cases) macroscopic nematode infections of the bronchial tract with Pseudalius
      inflexus and Torynurus convolutus, either singly or in combination, were
      recorded, and 106 (54 per cent) also had P inflexus within the pulmonary blood
      vessels. All the macroscopically parasitised porpoises were adults or juveniles
      although two neonates had histological evidence of nematode infection. There were
      62 cases of mild to severe, subacute to chronic bronchitis and bronchiolitis, 113
      cases of mild to severe chronic granulomatous interstitial pneumonia, and 34
      cases of mild to severe vasculitis or thrombovasculitis of pulmonary blood
      vessels attributable to these nematode infections. In 35 cases necropurulent or
      purulent (broncho)pneumonias were attributed either to secondary bacterial
      infections of the lungs or to septicaemias associated in seven cases with
      Streptococcus canis, in two cases with group B Salmonella species, in one case
      with Escherichia coli and in one case with Streptococcus lactis. The pulmonary
      lesions in 67 animals known or diagnosed to have been entrapped in fishing gear
      were non-specific and included persistent foam in the airways in 45 cases,
      diffuse congestion in 53, oedema in 50, and multifocal intra-alveolar haemorrhage
      in 33 cases. Seven cases of acute fibrinous or chronic fibrous pleuritis, seven
      cases of chronic necropurulent pneumonia associated with mycotic infections, four
      porpoises with traumatic lesions of the thorax and other parts of the body
      consistent with fatal attack from bottlenose dolphins (Tursiops truncatus), and
      one case of diffuse bronchointerstitial pneumonia associated with generalised
      morbillivirus infection were also recorded.

PMID- 10901215
TI  - Effects of short-term exposure to condensed tannins on adult Trichostrongylus
      colubriformis.
AB  - Twelve parasite-naive sheep were used to study the possible direct anthelmintic
      effect of a condensed tannin extract (quebracho) on the population and fecundity
      of the intestinal nematode Trichostrongylus colubriformis. The sheep were
      infected with a single dose of 20,000 L3 of T colubriformis. Twenty-eight days
      later, six of them were drenched daily for a week with quebracho extract at 8 per
      cent by weight of their food intake. All lambs were then slaughtered, and their
      small intestines removed to estimate the worm burdens and the numbers of eggs in
      utero. Two days after the first drench with tannin extract the faecal egg counts
      of the treated sheep were approximately 50 per cent of those of the control sheep
      (P<0.01), but there was no further reduction with continued drenching. In the
      treated sheep the worm burdens and number of eggs per gram faeces per worm were
      reduced by 30 per cent compared with the controls (P<0.05), but the sex ratios,
      the number of eggs in utero and length of the worms were not affected by
      drenching with tannin.

PMID- 10901216
TI  - Goat-sheep hybrid born under natural conditions in Botswana.
AB  - In Botswana it is common practice to rear goats (Capara hircus) and sheep (Ovis
      aries) together in one kraal. Under such conditions it is also not uncommon to
      see the two species mating, but such matings have never been reported to produce
      a viable offspring. In this field observation a viable offspring was born
      naturally from a mating between a female goat and a male sheep. Chromosomal
      analysis showed that the hybrid had 57 chromosomes, intermediate between the 60
      possessed by its dam and the 54 possessed by its sire. In August 1999 the hybrid
      was five years old.

PMID- 10901217
TI  - Biochemical and haematological parameters associated with tuberculosis in
      European badgers.

PMID- 10901218
TI  - Congenital bony ankylosis of the distal interphalangeal joint and distal sesamoid
      bone dysplasia in a horse.

PMID- 10901219
TI  - Retail sale of equine medicines.

PMID- 10901220
TI  - DNA testing for copper toxicosis in Bedlington terriers.

PMID- 10901221
TI  - Certificate in veterinary dermatology.

PMID- 10901222
TI  - Dew claw removal in Bernese mountain dogs.

PMID- 10901223
TI  - Avian influenza virus (H7 serotype) in a saker falcon in Italy.

PMID- 10901224
TI  - RCVS Council election.

PMID- 10901225
TI  - RCVS Council election.

PMID- 10901226
TI  - RCVS Council election.

PMID- 10901227
TI  - Choroid plexus in the central nervous system: biology and physiopathology.
AB  - Choroid plexuses (CPs) are localized in the ventricular system of the brain and
      form one of the interfaces between the blood and the central nervous system
      (CNS). They are composed of a tight epithelium responsible for cerebrospinal
      fluid secretion, which encloses a loose connective core containing permeable
      capillaries and cells of the lymphoid lineage. In accordance with its peculiar
      localization between 2 circulating fluid compartments, the CP epithelium is
      involved in numerous exchange processes that either supply the brain with
      nutrients and hormones, or clear deleterious compounds and metabolites from the
      brain. Choroid plexuses also participate in neurohumoral brain modulation and
      neuroimmune interactions, thereby contributing greatly in maintaining brain
      homeostasis. Besides these physiological functions, the implication of choroid
      plexuses in pathological processes is increasingly documented. In this review, we
      focus on some of the novel aspects of CP functions in relation to brain
      development, transfer of neuro-humoral information, brain/immune system
      interactions, brain aging, and cerebral pharmaco-toxicology.

PMID- 10901228
TI  - Insulin-like growth factor-I promotes myelination of peripheral sensory axons.
AB  - Insulin-like growth factor-I (IGF-I) in vivo or in the presence of other
      permissive factors can promote myelination in the central nervous system. In the
      current study, we examine the role of IGF-I in the myelination of peripheral
      nerves. In rat cocultures of dorsal root ganglia (DRG) and Schwann cells (SC)
      grown in serum- and insulin-free defined medium, IGF-I induces a dose dependent
      upregulation in myelin proteins such as P0, corresponding to maximal SC
      ensheathment. Furthermore, IGF-I is essential in promoting a dose-dependent, long
      term myelination of DRG sensory axons. In the absence of IGF-I, axons and SC
      survive, but fail to myelinate. In the presence of 10 nM IGF-I, 59% of axons are
      myelinated at 21 days, whereas in the absence of IGF-I myelination fails to
      occur. Maximum SC ensheathment occurs 48 hours after addition of IGF-I. If IGF-I
      is withdrawn at 48 hours, axon segregation by SC persists, however, most axons
      and SC do not exhibit a one-to-one relationship and little myelination is
      observed. IGF-I is important in myelination and is critical not only for initial
      SC ensheathment of the axon and upregulation of myelin proteins, but also for
      sustained myelination. Furthermore, IGF-I associated axonal size is not the sole
      determinant for myelination.

PMID- 10901230
TI  - Novel immunolocalization of alpha-synuclein in human muscle of inclusion-body
      myositis, regenerating and necrotic muscle fibers, and at neuromuscular
      junctions.
AB  - Alpha-synuclein (alpha-syn) is an important component of neuronal and glial
      inclusions in brains of patients with several neurodegenerative disorders.
      Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle
      disease of older patients. Its muscle phenotype shows several similarities with
      Alzheimer disease brain. A distinct feature of s-IBM pathology is specific
      vacuolar degeneration of muscle fibers characterized by intracellular amyloid
      inclusions formed by both amyloid-beta (Abeta) and paired-helical filaments
      composed of phosphorylated tau. We immunostained alpha-syn in muscle biopsies of
      s-IBM, disease-control, and normal patients. Approximately 60% of Abeta-positive
      vacuolated muscle fibers (VMF) contained well-defined inclusions immunoreactive
      with antibodies against alpha-syn. In those fibers. alpha-syn co-localized with
      Abeta, both by light microscopy, and ultrastructurally. Paired-helical filaments
      did not contain alpha-syn immunoreactivity. In all muscle biopsies, alpha-syn was
      strongly immunoreactive at the postsynaptic region of the neuromuscular
      junctions. alpha-syn immunoreactivity also occurred diffusely in regenerating and
      necrotic muscle fibers. In cultured human muscle fibers, alpha-syn and its mRNA
      were expressed by immunocytochemistry, immunoblots, and Northern blots. Our study
      provides the first demonstration that alpha-syn participates in normal and
      pathologic processes of human muscle. Therefore. its function is not exclusive to
      the brain and neurodegenerative diseases.

PMID- 10901229
TI  - Alpha-synuclein inclusions in amygdala in the brains of patients with the
      parkinsonism-dementia complex of Guam.
AB  - We investigated by immunohistochemistry the deposition of alpha-synuclein in the
      brains of deceased patients with the parkinsonism-dementia complex (PDC) of Guam.
      Five of 13 PDC brains showed numerous alpha-synuclein positive neuronal
      inclusions and abnormal neurites, chiefly in the amygdala. Similar alpha
      synuclein positive lesions were observed, although to a lesser extent, in the
      entorhinal cortex and the dorsal vagal nucleus. No alpha-synuclein positive
      inclusions were observed in motor cortex or locus coeruleus, and only a small
      number of positive inclusions were found in the Sommer's sector, temporal cortex,
      or substantia nigra. Some of the alpha-synuclein positive inclusions were
      reminiscent of cortical Lewy bodies (LB), but many of those in the amygdala
      coexisted with tau-positive pretangles and/or neurofibrillary tangles (NFT)
      within the same neurons. In these neurons, tau-positive shells encapsulated alpha
      synuclein positive central cores or irregularly shaped alpha-synuclein-positive
      deposition intermingled with pretangles/NFT. Thus, the present study suggests
      that a common mechanism may govern aggregation of alpha-synuclein and tau in the
      amygdala, and that aggregation of alpha-synuclein may play some role in the
      neurodegenerative process of a tauopathy (i.e. PDC) in which Abeta deposition is
      virtually absent.

PMID- 10901231
TI  - Pathogenesis of axonal degeneration: parallels between Wallerian degeneration and
      vincristine neuropathy.
AB  - Peripheral neuropathies and Wallerian degeneration share a number of pathological
      features; the most prominent of which is axonal degeneration. We asked whether
      common pathophysiologic mechanisms are involved in these 2 disorders by directly
      comparing in vitro models of axonal degeneration after axotomy or exposure to the
      neurotoxin vincristine. Embryonic rat dorsal root ganglia (DRG) were allowed to
      extend neurites for 5 days in culture, and then were either axotomized or exposed
      to 0.01 microM vincristine. Neurites universally degenerated by 3 days after
      axotomy or after 6 days of vincristine exposure. The neuroprotective effects of a
      low calcium environment or pharmacologic inhibition of the cysteine protease
      calpain were compared in these 2 models of axonal degeneration. Addition of EGTA
      or growth in zero-calcium media provided significant protection against axonal
      degeneration after either axotomy or vincristine exposure. Treatment with the
      experimental calpain inhibitor AK295 was equally protective in both models.
      Chronic exposure to AK295 was not toxic to the cultures. These data suggest that
      common mechanisms involving calcium and calpains are involved in both axotomy
      induced and vincristine-induced axonal degeneration. In addition, calpain
      inhibition may provide a strategy for preventing axonal degeneration and
      preserving neurologic function in a variety of PNS and CNS disorders.

PMID- 10901232
TI  - Characterization of a canine glioma cell line as related to established
      experimental brain tumor models.
AB  - A large animal tumor model for anaplastic glioma has been recently developed
      using immunotolerant allogeneic Beagle dogs and an established canine glioma cell
      line, J3T. This model offers advantages in terms of tumor morphology and
      similarity to human anaplastic glioma. The present study was aimed at evaluating
      the biological characteristics of the J3T canine glioma cell line as related to
      experimental gene therapy studies. Furthermore, development and morphology of
      canine brain tumors in a xenogeneic immunodeficient SCID mouse model was
      investigated. It was demonstrated that cultured J3T cells can be efficiently
      infected by adenovirus (AV), herpes-simplex type I (HSV), or retrovirus (RV)
      vectors, as well as by non-virus vectors such as cationic liposome/DNA complexes.
      Thus, in terms of infectability and transfectability, J3T cells seem to be closer
      to human glioma than the 9L rodent gliosarcoma. Cytotoxicity of selection
      antibiotics such as G418, puromycin, and hygromycin on J3T cells essentially
      resemble cytotoxicity seen with other established glioma lines, for example, 9L,
      U87, or U343. RV-mediated HSV-TK/GCV gene therapy demonstrated comparable LD50
      for TK-expressing and control (non-expressing) J3T and 9L cells treated with
      Ganciclovir. Further, it was proven that J3T cells are tumorigenic and may grow
      heterotopically and orthotopically in a xenogeneic immunodeficient host, the SCID
      mouse, although morphology and growth pattern of these xenogeneic tumors differ
      from the demonstrated invasive phenotype in the Beagle dog.

PMID- 10901233
TI  - Radiation-induced meningioma: a distinct molecular genetic pattern?
AB  - Radiation-induced meningiomas arise after low-dose irradiation treatment of
      certain medical conditions and are recognized as clinically separate from
      sporadic meningioma. These tumors are often aggressive or malignant, they are
      likely to be multiple, and they have a high recurrence rate following treatment
      compared with sporadic meningiomas. To understand the molecular mechanism by
      which radiation-induced meningioma (RIM) arise, we compared genetic changes in 7
      RIM and 8 sporadic meningioma (SM) samples. The presence of mutations in the 17
      exons of the neurofibromatosis type 2 (NF2) gene, which has been shown to be
      inactivated in sporadic meningiomas, was analyzed in RIM and SM using single
      strand conformation polymorphism (SSCP) and DNA sequencing. In contrast to SM,
      which showed NF2 mutations in 50% of specimens, no mutations were found in RIM.
      In addition, Western blot analysis of schwannomin/merlin protein, the NF2 gene
      product, demonstrated protein levels comparable to normal brain in 4/4 RIM tumor
      samples analyzed. Loss of heterozygosity (LOH) of genomic regions, which were
      reported for SM, was also analyzed in all cases of RIM using 22 polymorphic DNA
      markers. Allele losses were found on chromosomes 1p (4/7), 9p (2/7), 19q (2/7),
      22q (2/7), and 18q (1/7). From these observations we conclude that unlike
      sporadic meningiomas, NF2 gene inactivation and chromosome 22q deletions are far
      less frequent in RIM, and their role in meningioma development following low dose
      irradiation is less significant. Other chromosomal lesions, especially loss of
      1p, possibly induced by irradiation, may be more important in the development of
      these tumors.

PMID- 10901234
TI  - Neuropathological and histochemical changes in a multiple mitochondrial DNA
      deletion disorder.
AB  - The identification of cytochrome c oxidase (COX)-deficient/succinate
      dehydrogenase (SDH)- positive cells using sequential histochemistry has proved
      important in the identification of cells with high mitochondrial DNA (mtDNA)
      mutant load. We demonstrate large numbers of COX-deficient/SDH-positive neurons
      in a mosaic pattern throughout the CNS of a patient with a multiple mtDNA
      deletion disorder. This patient had prominent central and peripheral nervous
      system involvement with marked cerebellar ataxia, a parkinsonian extra-pyramidal
      movement disorder, external ophthalmoplegia, dysphagia, and a severe peripheral
      neuropathy. There was degeneration of myelin tracts in the cerebellum and dorsal
      spinal columns, diffuse astrocytosis, and selective neuronal degeneration
      particularly in the midbrain and cerebral microvacuolation. The proportional
      distribution of the COX-deficient neurons did not always correlate directly with
      the degree of neuropathological damage with regions of high neuronal loss having
      relatively low proportions of these cells. Other clinically affected CNS regions
      have high levels of COX-deficient neurons without significant cell loss. The role
      of these COX-deficient neurons in causing neuronal degeneration and clinical
      symptoms is discussed.

PMID- 10901236
TI  - Bioremediation of a soil contaminated by hydrocarbon mixtures: the residual
      concentration problem.
AB  - The phenomenon of residual concentration was investigated in the aerobic
      biodegradation of three different petroleum commercial products (i.e., kerosene,
      diesel fuel and a lubricating mineral oil) in static microcosms. Two different
      soils exhibiting different physical-chemical characteristics were used (i.e., a
      biologically treated hydrocarbon-contaminated soil and a pristine soil). Residual
      concentrations were observed and a simple way to take this phenomenon into
      account was proposed.

PMID- 10901235
TI  - Infiltration of hematogenous lineage cells into the demyelinating central nervous
      system of twitcher mice.
AB  - Infiltration of hematogenous lineage cells into the central nervous system (CNS)
      was investigated in the twitcher mouse, a murine model of globoid cell
      leukodystrophy in human. The hematogenous cells were selectively labeled
      following intraperitoneal injection of rhodamine isothiocyanate (RhIc). The
      frequency of detecting Rhlc-labeled cells (Rhlc+ cells) in the twitcher CNS
      varied with age. RhIc+ cells were hardly detected when injection was made prior
      to the postnatal day (PND) 30. The number of Rhlc' cells increased thereafter
      peaked at PND 35-38 and declined drastically at PND 40-45. The majority of RhIc+
      cells were distributed in white matter of the CNS that correlated well with the
      areas of demyelination and of increased microglia/macrophage population described
      in our earlier studies. Almost all Rhlc+ cells were double-labeled with antibody
      for Mac-1 and also with MHC class II. Some small cells double-labeled with RhIc
      and antibodies for CD4, CD8, or IL-2R were also identified. By RT-PCR, the
      expression of monocyte chemoattractant protein- (MCP-1) mRNA increased
      drastically at PND 30, peaked at PND 35, and decreased gradually after PND 40.
      This pattern of mRNA changes correlated well with the dynamic pattern of the
      infiltration of hematogenous cells into the CNS, suggesting a role of
      chemokine(s) in the cellular infiltration in the twitcher brain. The expression
      of IL-10 mRNA also increased gradually. IL-10 is a cytokine inhibitory factor and
      a major regulator in suppressing the inflammatory response. Thus, our results
      indicated that hematogenous lineage cells infiltrated in the CNS of twitcher
      mice, and that MCP-1 and IL-10 may play an important role in regulating the
      cellular recruitment.

PMID- 10901237
TI  - Pore structure of soot deposits from several combustion sources.
AB  - Soot was harvested from five combustion sources: a dodecane flame, marine and bus
      diesel engines, a wood stove, and an oil furnace. The soots ranged from 20% to
      90% carbon by weight and molar C/H ratios from 1 to 7, the latter suggesting a
      highly condensed aromatic structure. Total surface areas (by nitrogen adsorption
      using the Brunauer Emmett Teller, BET method) ranged from 1 to 85 m2 g(-1).
      Comparison of the surface area and meso-pore (pores 2-50 nm) surface area
      predicted by density functional theory (DFT) suggested that the soot was highly
      porous. Total meso-pore volume and surface area ranged from 0.004-0.08 cm3 g(-1)
      and from 0.33-6.9 m2 g(-1) respectively, accounting for up 33% of the BET surface
      area. The micro-pore volume (pores <2 nm) calculated from CO2 adsorption data (by
      DFT) ranged from 0.0009 to 0.013 cm3 g(-1) and micro-pore surface area was 3.1-41
      m2 g(-1), accounting for 10-20% of the total intra-particle (meso-plus micro
      pores) pore volume and 70-90% of the total intra-particle surface area. Higher
      pore volume and surface area values were computed using the Dubinin Radushkevich
      plot technique; ranging from 0.004-0.04 cm3 g(-1) to 11-102 m2 g(-1) for micro
      pore volume and surface area, respectively. Comparison of the C/H ratio and the
      micro-pore structure showed a strong correlation, suggesting a relationship
      between the condensation of the skeletal structure and micro-porosity of the
      soot. These data contradict literature reports that soot particles are non-porous
      and are consistent with recent literature reports that soil organic matter has
      large micro-pore surface areas.

PMID- 10901238
TI  - Photochemistry of hydrolytic iron (III) species and photoinduced degradation of
      organic compounds. A minireview.
AB  - On the basis of the research literature of the last fifty years, we have reviewed
      the photochemical properties of different hydrolytic Fe(III) species and the
      photodegradation of organic compounds in aqueous solutions initiated by them
      (mainly including low-molecular-weight Fe(III)-OH complexes, Fe(III) oxides
      (Fe2O3) and Fe(III) hydroxides (FeOOH)). Furthermore, the feasibility and
      prospects of the novel photochemical methods of using Fe(III) salts and oxides in
      wastewater treatments are being discussed in this paper.

PMID- 10901239
TI  - Decomposition of dihaloacetonitriles in water solutions and fortified drinking
      water samples.
AB  - An investigation of the decomposition of dihaloacetonitriles (DHANs) in water
      solutions and fortified drinking water samples was conducted. The concentrations
      of dichloroacetonitrile (CHCl2CN, DCAN), bromochloroacetonitrile (CHBrClCN, BCAN)
      and dibromoacetonitrile (CHBr2CN, DBAN) were determined by a gas chromatography
      mass spectrometry (GC-MS) method at regular time intervals and different
      temperatures. The effect of sodium thiosulfate (Na2S2O3), which is used as a
      preservative in water samples, was also examined. The rates of decomposition were
      determined for each compound. The results show that the reactions are faster in
      fortified drinking water samples than in ultrapure water solutions. They are also
      favored at higher temperature, especially when sodium thiosulfate is present. The
      highest decomposition rate is shown by DCAN, followed by BCAN and DBAN, while at
      the presence of sodium thiosulfate the decomposition of DBAN is the fastest.

PMID- 10901240
TI  - Ground discarded tires remove naphthalene, toluene, and mercury from water.
AB  - Ground discarded tires adsorb naphthalene, toluene, and mercury ions (Hg2+) from
      aqueous solutions. Their sorption properties and kinetics were determined by
      batch equilibration techniques at 20 degrees C. The isotherms were linear for
      naphthalene and toluene and their sorption coefficients were about 1340 and 255
      (ml/g), respectively. Sorption of the organic compounds by the ground rubber
      particles was relatively fast (within 30 min). However, the mercury isotherms
      were non-linear, and its sorption was slow as compared to the sorption of the
      organics. The rubber particles had a strong affinity for Hg2+. These results show
      that ground discarded tires are effective in removing organic compounds and Hg2+
      from wastewater and other contaminated environments. In addition it would be a
      useful, environmentally friendly use of discarded tires (one tire per year per
      capita is discarded in the United States).

PMID- 10901241
TI  - Decomposition of nitrous oxide on pillared clays.
AB  - Alumina-pillared smectites have been found to abate nitrous oxide in the presence
      of methane. The results indicate that the yield of the reaction (N20 --> N2 +
      (1/2)O2) increases when pillared clays are exchanged with transition metals,
      single-pass conversion rates of >70% being attainable. In particular, when double
      exchanged (calcium and subsequently copper) alumina pillared
      montmorillonite/beidellite is used as a catalyst, de-N2O activity reaches a
      maximum, which is maintained even after 4 h of work at a space velocity of 5.5 h(
      1). A mechanism for the reaction is suggested, which implies that N2O is first
      adsorbed by the catalyst and then decomposes through two different paths:
      catalyst oxidation and catalyst reduction. Such a redox process explains the
      kinetic data.

PMID- 10901242
TI  - Column study of the influence of air humidity on the retention of hydrocarbons on
      soil.
AB  - Inverse gas chromatography (IGC) is used for the analysis of the influence of air
      relative humidity on the retention of hexane, benzene, toluene and p-xylene in a
      sandy soil under experimental conditions similar to those typical of soil vapor
      extraction (SVE). The advantages of IGC over other techniques, are (a) an
      efficient use of lab resources, (b) a high sensitivity to low partitioning
      coefficients and (c) a closer reproduction of field conditions. In our procedure,
      experiments with only two samples of different mass are necessary to establish if
      linear isotherms can be used to describe the retention of the contaminants. This
      approach gives information necessary for analyzing the feasibility and design of
      remediation technologies with a laboratory effort significantly smaller than the
      adsorption/desorption cycle for isotherm determination. The retention
      coefficients of the contaminants decrease as humidity increases in a similar
      fashion for all of them, probably because the reduction in the number of the
      adsorption sites available for the organic compounds due to the presence of water
      is quite similar for all the contaminants studied. These retention coefficients
      may be related to those obtained for dry air conditions for all the contaminants
      through (R - 1)RH% = A(R - 1)dry air(B), where the parameter B is found to remain
      approximately constant (0.90), while the parameter A decreases linearly with the
      relative moisture.

PMID- 10901243
TI  - Kinetics and mechanism of color removal of methylene blue with hydrogen peroxide
      catalyzed by some supported alumina surfaces.
AB  - The catalyzed kinetics of the oxidative mineralization of the cationic dye
      methylene blue, phenothiazonium, 3,7-bis(dimethylamino)-chloride, with hydrogen
      peroxide were studied both in buffered and unbuffered solutions. The supported
      alumina catalysts used were in the form of copper(II), cobalt(II), manganese(II),
      and nickel(II)-ions. Also, some copper(II)-complexes were used, e.g. copper(II)
      ammine ([Cu(amm)4]2+), copper(II)-ethylenediamine ([Cu(en)2]2+) and copper(II)
      monoethanolamine ([Cu(mea)2]2+). The reaction is first order with respect to
      methylene blue. On the other hand, the order with respect to hydrogen peroxide is
      concentration range dependent. This range depends strongly on the catalyst used.
      At lower [H2O2], the order was 1 which then decreases with increasing [H2O2]
      passing through 0 at the maximum rate and finally becomes negative. This
      phenomenon is parallel to the formation of a colored intermediate on the surface
      of the catalyst. This suggests that the intermediate has an inhibiting effect on
      the rate of color removal. Moreover, the rate of the reaction was found to be
      strongly dependent on the pH of the solution and its ionic strength. It increases
      with increasing both pH and the concentration of added potassium chloride. Also,
      the rate of reaction is inhibited in presence of sodium dodecylsulfate anionic
      surfactant. The repeated use of the different catalysts showed that their
      catalytic activities are almost unaffected. A reaction mechanism was proposed
      with the formation of free radicals as reactive intermediates.

PMID- 10901244
TI  - The formation and control of disinfection by-products using chlorine dioxide.
AB  - In this study, chlorine dioxide (ClO2) was used as an alternative disinfectant
      with vanillic acid, p-hydroxybenzoic acid, and humic acid as the organic
      precursors in a natural aquatic environment. The primary disinfection by-products
      (DBPs) formed were trihalomethanes (THMs) and haloacetic acids (HAAs). Under
      neutral conditions (pH = 7) for vanillic acid, more total haloacetic acids
      (THAAs) than total trihalomethanes (TTHMs) were found, with a substantial
      increase during the later stages of the reaction. In the case of p-hydroxybenzoic
      acid, the amount of THAAs produced was minimal. Raising the concentration of ClO2
      was not favorable for the control of THAAs in low concentrations of vanillic
      acid. ClO2 could reduce the total amount of TTHMs and THAAs for higher
      concentration of vanillic acid. It was found that the humic acid treatment dosage
      was not significant. Under alkaline conditions (pH = 9), the control of TTHMs and
      THAAs for the treatment of vanillic acid was better and more economical, however,
      an appreciable amount of inorganic by-products were observed. Under the same
      alkaline condition, the control of THAA for the treatment of p-hydroxybenzoic
      acid was not beneficial and for the treatment of humic acid was not significant.

PMID- 10901245
TI  - Replacement of H2O2 by O2 in Fenton and photo-Fenton reactions.
AB  - The consumption of oxygen during the degradation of aniline by Fenton and photo
      Fenton reactions is studied. The effect that parameters like aniline, Fe(II) and
      H2O2 initial concentration, pH, temperature and O2 flow rate have on the ratio O2
      consumed/H2O2 consumed is examined. The determination of those combinations of
      experimental conditions for which an effective partial replacement of H2O2 by O2
      as electron acceptor takes place is investigated. The results show that this
      replacement takes place in a variable extent, but the presence of H2O2 is
      necessary along the reaction, and the maximum consumption of O2 only takes place
      when the ratio amount of aniline mineralized vs. initial aniline concentration is
      minimal.

PMID- 10901246
TI  - Photocatalytic degradation of cellulose bleaching effluent by supported TiO2 and
      ZnO.
AB  - A cellulose bleaching effluent (E1) was degraded in batch conditions by
      photocatalysis using TiO2 and ZnO supported on glass Raschig rings. The effluent
      was completely decolourised and the total phenol content was reduced by 85% after
      120 min treatment with both catalysts. Partial mineralization of the organic
      matter was confirmed by total organic carbon (TOC) reduction, approximately 50%.
      The residual organic matter shows a low acute toxicity as compared to the initial
      values and AOX values are strongly reduced after the photocatalytic oxidation.
      Molecular mass distribution showed that high molecular mass compounds were almost
      completely degraded.

PMID- 10901248
TI  - Destruction of phenol aqueous solution by photocatalysis or direct photolysis.
AB  - The photodegradation of phenol has been investigated under a high-pressure
      mercury lamp with a kind of jacket (glass or quartz) depending on used UV light
      range and a variety of experimental conditions: UV (lambda > 200 nm) with oxygen
      or with TiO2 and oxygen or with N2; UV (lambda > 330 nm) with oxygen or with TiO2
      and oxygen or with N2. Photocatalysis and direct photolysis of phenol have
      different reaction pathways. Direct photolysis of phenol yielded a brown-yellow
      complex organic polymer in both aerobic and anaerobic environments. The polymer
      cannot be mineralized in an anaerobic environment. The effects of catalyst amount
      and oxygen concentration in the reaction atmosphere on the destruction of phenol
      were studied. The results prove that an appropriate catalyst amount can avoid
      direct photolysis and increase the mineralization rate of phenol.

PMID- 10901247
TI  - The study of lag phase and rate improvement of TCE decay in UV/surfactant
      systems.
AB  - The photodegradation of trichloroethene (TCE) in surfactant micelles was
      investigated. The decay of TCE was studied in the Rayonet RPR-200 merry-go-round
      photoreactor, at 253.7 nm monochromatic ultraviolet (UV) lamps, in the presence
      of surfactants. Surfactants are used as additional hydrogen sources to improve
      the photodegradation rates of TCE. About three times the rate increment is
      observed in the presence of Brij 35 surfactant micelles than in water alone. The
      increasing concentrations of H+ and Cl- indicate that they are the final products
      of TCE photodegradation (i.e. photodechlorination is the dominant mechanism in
      this system). A lag phase is observed at the beginning of the degradation, but
      the duration of the lag phase is apparently reduced as the initial pH increases.
      Because the overall decay of TCE is also found faster at higher pH levels, it is
      suggested that the free radical reaction is dominant at high pH levels, and the
      formation of lag phases is mainly due to the deficiency of free radicals at lower
      pH levels. The photodecomposition of TCE in surfactant micelles is also proven to
      be a clean and effective process. It generates no chlorinated by-products or
      intermediates during the process, and TCE is fully decomposed within a reasonable
      time.

PMID- 10901249
TI  - Formation of hydroxylated and dimeric intermediates during oxidation of
      chlorinated phenols in aqueous solution.
AB  - The oxidation of selected chlorophenols (2-chlorophenol, 4-chlorophenol, 2,4
      dichlorophenol, 2,4,6-trichlorophenol, 2,3,4,6-tetrachlorophenol and
      pentachlorophenol) was studied in aqueous solutions using UV/H2O2 and O3 methods.
      The formation of oxidation intermediates was measured to elucidate their
      importance in the treatment of chlorophenols. Results indicated that
      chlorophenols can be treated efficiently by the methods studied, but the
      dechlorination of the compounds was insufficient. Analysis of intermediates in
      the acetylated extraction fractions showed that hydroxylation of chlorophenols
      and formation of dimeric products were involved in the oxidation of chlorophenols
      in both treatment processes. The majority of the intermediates detected were
      transient, and thus were not detectable after an extended treatment time. The
      presence of a complicated mixture of intermediates suggests the need for toxicity
      testing to confirm the detoxifying effect of the chemical oxidation of
      chlorophenols.

PMID- 10901250
TI  - Photocatalytic oxidation of gaseous chlorinated organics over titanium dioxide.
AB  - The photocatalytic oxidation of high levels of volatile chlorinated organic
      compounds in gas phase has been studied using a specially designed photoreactor.
      The influence of light intensity, initial water vapour concentration,
      temperature, inlet contaminant concentration and flow rate on destruction
      efficiency has been investigated. The performance of the titanium catalyst was
      strongly affected by the presence of water in the air stream. Experiments have
      been most successfully conducted at room temperature, low initial contaminant
      concentrations, low flow rates and high light intensities. Several by-products
      have been detected performing photocatalytic degradation of trichloroethylene
      (TCE) and tetrachloroethylene (PCE). No catalyst deactivation was observed.

PMID- 10901251
TI  - Diffusion of hydrogen sulfide and methyl mercaptan onto microporous alkaline
      activated carbon.
AB  - Activated carbon kinetic studies show that both H2S and CH3SH yielded pore
      diffusion coefficients from 10(-6) to 10(-8) cm2/s. Results indicated that pore
      structures could influence effective diffusivity. Under the same adsorbate
      concentration, CH3SH exhibited a greater effective pore diffusion coefficient
      than H2S. This may be attributed to the fact that CH3SH has both polar (-SH) and
      non-polar (-CH3) functional groups and dissolves into water easier, thus
      providing more attraction for the activated carbon surface. In addition, the
      saturation vapor pressure of CH3SH is lower than that of H2S. Therefore, CH3SH is
      easier to adsorb onto activated carbon than H2S.

PMID- 10901252
TI  - Degradation mechanism of azo dye C. I. reactive red 2 by iron powder reduction
      and photooxidation in aqueous solutions.
AB  - We have made a comparison of the UV-VIS spectra of three azo dyes, C. I. reactive
      red 2, orange II and C. I. reactive black 8, in aqueous solutions during
      treatment with iron powder reduction and photooxidation. From this, we propose
      their mechanisms for reduction photooxidation. GC/MS analyses of the degradation
      products of the dye C. I. reactive red 2 demonstrated some important steps
      producing hydrogenated azo structure, substituted benzene and substituted
      naphthalene.

PMID- 10901253
TI  - Degradation of ethinyl estradiol by nitrifying activated sludge.
AB  - Degradation of ethinyl estradiol (EE2) by nitrifying activated sludge was studied
      with micro-organisms grown in a reactor with feedback of sludge fed with only a
      mineral salts medium containing ammonium as the sole energy source. Ammonium was
      oxidised by this sludge at a rate of 50 mg NH4+ g(-1) DW h(-1). This activated
      sludge was also capable of degrading EE2 at a maximum rate of 1 microg g(-1) DW
      h(-1). Using sludge with an insignificant nitrifying capacity of 1 mg NH4+ g(-1)
      DW h(-1), no degradation of EE2 was detected. Oxidation of EE2 by nitrifying
      sludge resulted in the formation of hydrophilic compounds, which were not further
      identified. Most probably degradation by nitrifying sludge results in a loss of
      estrogenic activity, as hydroxylated derivatives of EE2 are known to have a
      substantially lower pharmacological activity than EE2.

PMID- 10901254
TI  - Microbial degradation of phthalic acid esters under anaerobic digestion of
      sludge.
AB  - The microbial degradation by anaerobic sludge of three phthalates, priority
      pollutants, listed by both China National Environmental Monitoring Center and the
      U.S.EPA, namely, dimethyl (DMP), di-n-butyl (DBP) and di-n-octyl (DOP) phthalates
      was investigated. The experimental results indicated that the biodegradation rate
      and the biodegradability of three phthalates under anaerobic conditions appeared
      to be related to the length of the alkyl-side chains. More than 90% of DMP and
      DBP with the short alkyl-side chain phthalates can be degraded, whereas the DOP
      degradation appeared to be relatively slow under the same experimental
      conditions. The quantity of methane produced was measured and the results showed
      that both the ester groups and the phthalate ring were mineralized at a
      significant rate. The kinetics study demonstrated that the biodegradation of
      three phthalates conformed to the first-order model with respect to their
      concentrations.

PMID- 10901255
TI  - Adsorption/desorption properties of copper ions on the surface of iron-coated
      sand using BET and EDAX analyses.
AB  - This study was conducted to develop a heating process for coating hydrated iron
      oxide on the sand surface to utilise the adsorbent properties of the coating and
      the filtration properties of the sand. BET and scanning electron microscope (SEM)
      analyses were used to investigate the surface properties of the coated layer. An
      energy dispersive X-ray (EDAX) technique of analysis was used for characterising
      metal adsorption sites on the iron-coated sand surface. The results indicated
      that the iron-coated sand had more micropores and higher specific surface area
      because of the attachment of iron oxide. Copper ions could penetrate into the
      micropores and mesopores of iron oxide on sand surface, and the regeneration of
      the iron-coated sand could be achieved by soaking with pH = 3.0 acid solution.
      Besides, the results of EDAX analysis showed that copper ions were chemisorbed on
      the surface of iron-coated sand. Results of the study developed an innovative
      technology for coating iron oxide on sand surface for the treatment of heavy
      metal in water.

PMID- 10901256
TI  - Bacterial response to photocatalytic degradation of 6-chlorovanillin.
AB  - The oxidation of a 186 ppm 6-chlorovanillin solution was performed using
      impregnated TiO2 glass rings in a 1 l photochemical reactor. Fifty per cent
      degradation was obtained after 60 min with recirculation of the solution. Then,
      oxidised samples were submitted under aerobic conditions to bacterial degradation
      in the Pseudomonas paucimobilis (S37) and Burkholderia cepacia (PZK). Both
      selected aerobic bacteria degrade more efficiently the photocatalysed samples,
      being PZK strain better than S37. A first-order kinetic was observed in both
      systems photocatalytic and bacterial degradation.

PMID- 10901257
TI  - The enhancement methods for the degradation of TCE by zero-valent metals.
AB  - Batch tests were performed to compare the degradation rates of TCE on Fe0 and
      Zn0. Our results indicated that the degradating capability of Zn0 to TCE was
      nearly 10 times higher than that of Fe0. On the other hand, the degradation rates
      of Fe0 or Zn0 in conjunction with other metals for reduction of TCE was
      investigated. The selected metals were nickel (Ni0) and palladium (Pd0) both of
      which have a strong enhancement effect. The reduction rates of Zn0/Pd0 and
      Zn0/Ni0 for TCE were the fastest. Fe0 that had lost its surface activity could be
      activated again by the addition of Pd0 or Ni0.

PMID- 10901258
TI  - Contribution of free radicals to chlorophenols decomposition by several advanced
      oxidation processes.
AB  - The chemical decomposition of aqueous solutions of various chlorophenols (4
      chlorophenol (4-CP), 2,4-dichlorophenol (2-DCP), 2,4,6-trichlorophenol (2,4,6
      TCP) and 2,3,4,6-tetrachlorophenol (2,3,4,6-TeCP)), which are environmental
      priority pollutants, is studied by means of single oxidants (hydrogen peroxide,
      UV radiation, Fenton's reagent and ozone at pH 2 and 9), and by the Advanced
      Oxidation Processes (AOPs) constituted by combinations of these oxidants (UV/H2O2
      UV/Fenton's reagent and O3/UV). For all these reactions the degradation rates are
      evaluated by determining their first-order rate constants and the half-life
      times. Ozone is more reactive with higher substituted CPs while OH* radicals
      react faster with those chlorophenols having lower number of chlorine atoms. The
      improvement in the decomposition levels reached by the combined processes, due to
      the generation of the very reactive hydroxyl radicals. in relation to the single
      oxidants is clearly demonstrated and evaluated by kinetic modeling.

PMID- 10901259
TI  - Forces dictating colloidal interactions between viruses and soil.
AB  - The fate and transport of viruses in soil and aquatic environments were studied
      with respect to the different forces involved in the process of sorption of these
      viruses on soil particles. In accordance with the classical DLVO theory, we have
      calculated the repulsive electrostatic forces and the attractive van der Waals
      forces. Bacteriophages have been used as model sorbates, while different clays
      have been used as model sorbents. The equations used for the determination of the
      change in free energy for the process (deltaG) takes into consideration the
      roughness of the sorbent surfaces. Results indicate that attractive van der Waals
      forces predominate the process of sorption of the selected bacteriophages on
      clays.

PMID- 10901260
TI  - Decolorization of textile wastewater by photo-fenton oxidation technology.
AB  - This paper describes the use of photo-fenton process for color removal from
      textile wastewater stream. The wastewater sample to be treated was simulated by
      using colorless polyvinyl alcohol (PVA) and reactive dyestuff of R94H. As a
      result, the hydroxyl radical (HO*) oxidation can effectively remove color, but
      the chemical oxygen demand (COD) was removed in a slight degree. The color
      removal is markedly related with the amount of HO* formed. The optimum pH for
      both the OH* formation and color removal occurs at pH 3-5. Up to 96% of color can
      be removed within 30 min under the studied conditions. Due to the photoreduction
      of ferric ion into ferrous ion, color resurgence was observed after 30 min. The
      ferrous dosage and UV power affect the color removal in a positive way, however,
      the marginal benefit is less significant in the higher range of both. PVA as the
      major background COD of a textile wastewater stream inhibits the color removal
      insignificantly as its concentration increases.

PMID- 10901261
TI  - Effects of surfactants on extraction of phenanthrene in spiked sand.
AB  - Problems associated with polynuclear aromatic hydrocarbon (PAH) contaminated site
      in environmental media have received increasing attention. To resolve such
      problems, innovative in situ methods are urgently required. This work
      investigated the feasibility of using surfactants to extract phenanthrene on
      spiked sand in a batch system. Phenanthrene was spiked into Ottawa sand to
      simulate contaminated soil. Six surfactants, Brij 30 (BR), Triton X-100 (TR),
      Tergitol NP-10 (TE), Igepal CA-720 (IG), sodium dodecyl sulfate (SDS) and
      hexadecyl trimethyl ammonium bromide (HTAB) were used. Adjusting the extraction
      time, mixing speed and surfactant concentration yielded the optimum extracting
      conditions. The concentration of phenanthrene was identified with HPLC. Under the
      experimental conditions, results indicated that those surfactants were highly
      promising on site remediation since the residual phenanthrene concentration was
      effectively reduced. The optimum operating conditions were obtained at 30 min,
      125 rpm and surfactant concentrations in 4%.

PMID- 10901262
TI  - Sodium dodecyl sulphate-enhanced desorption of atrazine: effect of surfactant
      concentration and of organic matter content of soils.
AB  - A study was made of the adsorption-desorption of atrazine in aqueous medium in
      five soils with organic matter (OM) contents in the range 1.4-10.3% and also of
      the desorption of the herbicide in aqueous solutions of the anionic surfactant
      sodium dodecyl sulphate (SDS) at critical micelle concentrations (cmc) of 0.75,
      1.50, 5 and 10. The adsorption and desorption isotherms in water together with
      the desorption isotherms in SDS solutions with concentrations of 0.75 and 1.50
      cmc fit the Freundlich adsorption equation. All the desorption isotherms
      displayed hysteresis. The increase or reduction in hysteresis of the desorption
      isotherms in SDS solutions with respect to those of desorption in water depend on
      the SDS concentration and on the OM content of the soils. Below the cmc, SDS only
      increases the desorption of atrazine in the soil with the highest OM content
      (10.3%). However, above the cmc (5 and 10 cmc) the desorption of atrazine
      increases in all soils, the efficiency of desorption increasing with the OM
      content of the soils.

PMID- 10901263
TI  - Kinetics of reductive denitrification by nanoscale zero-valent iron.
AB  - Zero-valent iron powder (Fe0) has been determined to be potentially useful for
      the removal of nitrate in the water environment. This research is aimed at
      subjecting the kinetics of denitrification by nanoscale Fe0 to an analysis of
      factors affecting the chemical denitrification of nitrate. Nanoscale iron
      particles with a diameter in the range of 1-100 nm, which are characterized by
      the large BET specific surface area to mass ratio (31.4 m2/g), removed mostly 50,
      100, 200, and 400 mg/l of nitrate within a period of 30 min with little
      intermediates. Compared with microscale (75-150 microm) Fe0, end product is not
      ammonia but N2 gas. Kinetics analysis from batch studies revealed that the
      denitrification reaction with nanoscale Fe0 appeared to be a pseudo first-order
      with respect to substrate and the observed reaction rate constant (k(obs)) varied
      with iron content at a relatively low degree of application. The effects of
      mixing intensity (rpm) on the denitrification rate suggest that the
      denitrification appears to be coupled with oxidative dissolution of iron through
      a largely mass transport-limited surface reaction (<40 rpm).

PMID- 10901264
TI  - Human immunodeficiency virus glycoprotein 160 induces cytokine mRNA expression in
      the rat central nervous system.
AB  - 1. Elevated proinflammatory cytokines within the central nervous system (CNS) of
      individuals infected with human immunodeficiency virus (HIV) may contribute to
      altered CNS processes prior to the onset of AIDS. Most studies of HIV-induced
      alterations in cytokine expression within the CNS have focused on interleukin
      (IL)-1 and tumor necrosis factor (TNF). 2. We used a ribonuclease protection
      assay (RPA) to elucidate further the pattern of cytokine mRNA expression in the
      rat CNS in response to HIV envelope glycoprotein 160 (gp160). Male Sprague-Dawley
      rats were surgically implanted with a guide cannula directed into a lateral
      cerebral ventricle. HIV gp160 was injected intracerebroventricularly and rats
      were sacrificed immediately (time = 0) or at 1, 2, or 4 hr postinjection.
      Discrete brain regions were dissected, and peripheral glands removed. All tissues
      were frozen in liquid nitrogen until RNA extraction and assay. 3. IL-1beta IL
      1alpha, TNF-alpha, and TNFbeta mRNAs were constitutively expressed in brain
      tissues. Central administration of gp160 dramatically increased mRNA expression
      for IL-1beta and TNFalpha in the hypothalamus, hippocampus, brainstem, and
      cerebellum. Furthermore, although mRNA expression for IL-5, IL-6, and IL-10 was
      never detected under basal conditions, these mRNAs were increased in brain tissue
      after administration of gp160. Peak expression in each brain region was detected
      2 hr after administration. Multiple cytokine mRNAs were detected in peripheral
      tissues, but their expression was not altered by central administration of gp160.
      4. Our results indicate that gp160 induces mRNA expression in brain for cytokines
      other than IL-1 and TNF. Screening for multiple cytokine mRNA in this manner
      provides extensive information concerning the particular cytokines that may be
      involved in HIV-induced pathologies and alterations in CNS processes.

PMID- 10901265
TI  - Neuronal cell death and reactive oxygen species.
AB  - 1. We have investigated the role of reactive oxygen species (ROS) in cell death
      induced by ischemia or application of the excitatory amino acid agonist, N-methyl
      D-aspartate (NMDA) or kainate (KA), in acutely isolated rat cerebellar granule
      cell neurons, studied by flow cytometry. Various fluorescent dyes were used to
      monitor intracellular calcium concentration, ROS concentration, membrane
      potential, and viability in acutely dissociated neurons subjected to ischemia and
      reoxygenation alone, NMDA or kainate alone, and ischemia and reoxygenation plus
      NMDA or kainate. 2. With ischemia followed by reoxygenation, ROS concentrations
      rose slightly and there was only a modest increase in cell death after 60 min. 3.
      When NMDA or kainate alone was applied to the cells there was a large increase in
      ROS and in intracellular calcium concentration but only a small loss of cellular
      viability. However, when NMDA or kainate was applied during the reoxygenation
      period there was a large loss of viability, accompanied by membrane
      depolarization, but the elevations of ROS and intracellular calcium concentration
      were not greater than seen with the excitatory amino acids alone. 4. These
      observations indicate that other factors beyond ROS and intracellular calcium
      concentration contribute to cell death in cerebellar granule cell neurons.

PMID- 10901266
TI  - Regulation of the phosphorylation state of the AMPA receptor GluR1 subunit in the
      postsynaptic density.
AB  - 1. Changes in the phosphorylation state of AMPA-type glutamate receptors are
      thought to underlie activity-dependent synaptic modification. It has been
      established that the GluR1 subunit is phosphorylated on two distinct sites, Ser
      831 and Ser-845, by CaMKII and by PKA, respectively, and that phosphorylation by
      either kinase correlates with an increase in the AMPA receptor-mediated current.
      GluR1 is concentrated in postsynaptic densities and it is expected that this
      particular receptor pool is involved in synaptic modification. The present study
      describes the regulation of the phosphorylation state of GluR1 in isolated
      postsynaptic densities. 2. Addition of Ca2+/calmodulin to the postsynaptic
      density fraction promotes phosphorylation of GluR1, and under these conditions,
      dephosphorylation is prevented by the inclusion of phosphatase type 1 inhibitors,
      microcystin-LR and Inhibitor-1. CaMKII and phosphatase type 1 are also found to
      be enriched in the PSD fraction compared to the parent fractions. 3. On the other
      hand, the addition of cAMP, either by itself or with exogenous PKA, does not
      change the phosphorylation state of GluR1. Prior incubation of PSDs under
      dephosphorylating conditions results in only a small PKA-mediated phosphorylation
      of GluR1. 4. These results support the hypothesis that PSDs contain the molecular
      machinery to promote the phosphorylation as well as the dephosphorylation of
      GluR1 on Ser-831, while Ser-845, the site phosphorylated by PKA, appears to be
      mostly occluded. Thus, it is possible that a large pool of PSD-associated GluR1
      is regulated through modification of the phosphorylation state of the Ser-831
      site only.

PMID- 10901267
TI  - Changes of cytochemical markers in the conjunctival and corneal epithelium after
      corneal debridement.
AB  - 1. The aim of this study was to determine the epithelial changes of the
      conjunctiva and cornea up to 7 days after corneal debridement and the changes
      highlighted included (1) proliferation, (2) production of growth factor, (3)
      changes in calcium binding protein marker, (4) production of cytokine, and (5)
      maturity of the regeneration corneal epithelium. 2. The cytochemical changes of
      the corneal and conjunctival epithelia of rabbit were analyzed up to 7 days after
      debridement. 3. An increase in proliferating cell nuclear antigen (PCNA) was
      observed in the limbal epithelia 12 hr after lesion and reached a peak by 48 hr.
      4. Some proliferating limbal cells also contained epidermal growth factor (EGF)
      beginning 24 hr after injury. The early limbal cell proliferation and the EGF
      production and their persistence until 7 days after lesion were likely involved
      with the process of regeneration. 5. Other positive markers appeared after lesion
      included tumor necrosis factor (TNFalpha) and calcium binding proteins S100A and
      S100B, which appeared mainly within the first 48 hr after lesion and then started
      to decline. The short appearance and the relatively small quantity of TNFalpha
      indicated that this cytokine was probably not very important in the repair
      process and its appearance might be related to the injury induced. The presence
      of S100A and S100B could be associated with both cell death after injury and the
      proliferation of new epithelium. 6. The cornea epithelium was still immature 7
      days after lesion in that it still contained cytokeratin. 7. In conclusion, the
      critical hours of peak conjunctival and corneal changes after corneal debridement
      were in the first 2 days.

PMID- 10901268
TI  - Immunolesioning of glutamate receptor GluR1-containing neurons in the rat
      neostriatum using a novel immunotoxin.
AB  - 1. To investigate the potency of a novel immunotoxin that is specific for
      glutamate receptor GluR1, a subunit of the alpha-amino-3-hydroxy-5-methyl-4
      isoxazole-propionate (AMPA)-type receptor channel, immunolesioning was performed.
      2. A ribosome-inactivating protein, trichosanthin (TCS), was isolated and
      conjugated to the goat anti-rabbit IgG antibody molecule. The anti-rabbit
      antibody-TCS complex was preincubated with GluR1-specific rabbit antibody to
      produce a GluR1-specific immunotoxin. The immunotoxin was unilaterally
      administered into either the neostriatum or the lateral ventricle of rats. 3.
      Immunoreactivity for GluR1 or GluR4 was revealed in perfuse-fixed sections of the
      neostriatum obtained from the lesioned and control animals by
      immunocytochemistry. After ventricular or striatal injections of the immunotoxin,
      depletions of GluR1-immunoreactive neurons, the presumed GABAergic interneurons
      in the neostriatum, were found. Depletions of GluR4-immunoreactive perikarya, the
      presumed same subpopulation of striatal interneurons, were also found. In
      addition, no change in the pattern of distribution of immunoreactivity for GluR2
      or glial fibrillary acidic protein was found in the lesioned neostriatum. These
      results indicate that the novel GluR1 immunotoxin is potent and specific. 4. In
      addition, striatal application of the immunotoxin caused a greater depletion in
      the number of GluR1-immunoreactive neurons. The present results also indicate
      that the route of immunotoxin application may be important in producing specific
      lesions.

PMID- 10901269
TI  - Phosphorylation of tau alters its association with the plasma membrane.
AB  - 1. The potential functions of the microtubule-associated protein tau have been
      expanded by the recent demonstration of its interaction with the plasma membrane.
      Since the association of tau with microtubules is regulated by phosphorylation,
      herein we examine whether or not the association of tau with the plasma membrane
      is also regulated by phosphorylation. 2. A range of tau isoforms migrating from
      46 to 64 kDa was associated with crude particulate fractions derived from SH-SY
      5Y human neuroblastoma cells, and were retained during the initial stages of
      plasma membrane purification. During the extensive washing utilized in
      purification of the plasma membrane, portions of each of these isoforms were
      depleted from the resultant purified membrane. Immunoblot analysis with phospho
      dependent and -independent antibodies revealed selective depletion of phospho
      isoforms during membrane washing. This effect was more pronounced for the slowest
      migrating (64-kDa) tau isoform. 3. This putative influence of phosphorylation on
      the association of tau with the plasma membrane was further probed by
      transfection of SH-SY-5Y human neuroblastoma cells with a tau construct that
      could associate with the plasma membrane but not with microtubules. Treatment
      with phorbol ester or calcium ionophore, both of which increased phospho-tau
      levels within the cytosol and plasma membrane, was accompanied by the
      dissociation of this tau construct from the membrane. 4. These data indicate that
      phosphorylation regulates the association with the plasma membrane. Dissociation
      from the membrane by phosphorylation may place tau at risk for
      hyperphosphorylation and ultimate PHF formation in a manner previously considered
      for tau dissociated from microtubules.

PMID- 10901270
TI  - The use of competitive PCR mimic to evaluate a Limulus lambda phage genomic DNA
      library.
AB  - 1. A lambda phage genomic DNA library for Limulus (L.) polyphemus brain was
      constructed using the AGEM-12 vector and the host strain KW251. 2. The primary
      library contained approximately 1.275 x 10(6) independent clones, increasing upon
      amplfication to 6.66 x 10(9) pfu/ml in a total volume of 58 ml. 3. A total of 28
      clones was randomly chosen for a determination of the average size of inserts in
      the library. All clones contained inserts and the average size was 14.9 kb,
      ranging from 11.7 to 28.0 kb. The library provides a 10-fold equivalent of the L.
      polyphemus genome. 4. A new approach for evaluating a genomic DNA library was
      developed, in which competitive PCR MIMIC was employed to determine the target
      gene copy number in both constructed library and brain genomic DNA. The putative
      protein kinase C epsilon (PKCepsilon) was selected as the target gene because its
      partial sequence of cDNA was recently cloned from L. polyphemus brain in our
      laboratory (Cao et al., 1998). A 419-bp fragment of nonhomologous sequence
      derived from putative PKCepsilon and a 306-bp fragment from plasmid pUC 18 were
      generated for use as target and competitor in PCR MIMIC, respectively. 5. Within
      the genomic library DNA, a 0.8 value was obtained for the copy number of the
      putative PKCepsilon gene that was detected in 0.1 amol of one equivalent L.
      polyphemus genome in terms of the average recombinant molecular weight. In the
      genomic DNA, a single copy of putative PKCepsilon was found in 0.1 amol of one
      coverage for the L. polyphemus genome. Thus, it was implied that nearly 80%
      genetic resource was incorporated into the library. This percentage was termed
      the incorporation rate. 6. Based on these findings, we suggest that the
      incorporation rate is an essential factor for evaluating genomic libraries,
      particularly, when using partial digestion with restriction enzymes for library
      construction.

PMID- 10901272
TI  - Data mining techniques applied to medical information.
AB  - Knowledge discovery from the dramatically increased data of an auto-stored
      medical information system is still in its infancy. The purpose of this study is
      to use widely available and easily operated techniques that can satisfy general
      users in extracting specific knowledge to make the medical information system
      more functional. Data mining techniques, including data visualisation,
      correlation analysis, discriminant analysis, and neural networks supervised
      classification, were applied to heart disease databases. These techniques can
      help to identify high risk patients, define the most important factors
      (variables) in heart disease, and build a multivariate relationship model to show
      the relationship between any two variables in a way that such relationships are
      easy to view. Simple visualization techniques were utilised to construct this
      model, which corresponds with current medical knowledge. Two nonparametric
      (distribution assumption free) classification tools were employed to identify
      high risk heart disease patients. Both the neural networks supervised
      classification methods and the discriminant analysis method produced reliable
      classification rates for heart disease patients. However, neural networks yielded
      a higher percentage of correct classifications (averaging 89%) than discriminant
      analysis (79%). Data visualisation and correlation analysis resulted in similar
      conclusions regarding the most important factors in heart disease. These data
      mining tools provide simple and effective methods of extracting knowledge from
      general medical information. The treatment of missing data is also discussed.

PMID- 10901271
TI  - The delay in recovery from fast inactivation in skeletal muscle sodium channels
      is deactivation.
AB  - 1. Using macropatch techniques, we tested the assumption that deactivation
      underlies the observed delay in the onset to recovery from fast inactivation by
      comparing open-state deactivation to recovery delay for rat skeletal muscle
      mutations R1441C and R1441P. 2. Deactivation kinetics from the open state were
      determined from the exponential decay of tail currents. R1441C and R1441P
      prolonged open-state deactivation, with the greatest effect produced by R1441P.
      3. Delays in the onset to recovery from fast inactivation for R1441P and for
      R1441C were abbreviated compared to those for rSkM1. Recovery delay was longer in
      R1441P than R1441C at voltages more negative than -110 mV. Recovery from
      inactivation exhibited a voltage dependence which, unlike delay, saturated at
      depolarized voltages. Recovery rate constants were increased to a similar extent
      for R1441C and R1441P at -150 to -120 mV compared to rSkM1. 4. These results
      indicate that the delay in the onset to recovery from fast inactivation in
      skeletal muscle sodium channels is due to deactivation. Lessening of charge
      immobilization for R1441C and R1441P may contribute to observed biophysical
      defects underlying the hyperexcitability of muscle fibers containing paramyotonia
      congenita mutations. The second stage of recovery from fast inactivation may be
      affected differentially by these mutations.

PMID- 10901273
TI  - Initial use of a computer system for assisting dermatological diagnosis in
      general practice.
AB  - The accuracy of skin lesion description by 24 general practitioners was assessed
      as they used a computer diagnosis assistance system (DERMIS). Descriptive
      accuracy determines the quality of advice. Only four doctors showed a trend to
      accurate description over 25 hospital referrals.

PMID- 10901274
TI  - Modelling and reclassification of surgical procedures--experiences from the use
      of GALEN methods in the domain of thoracic surgery.
AB  - This paper reports on experiences from the evaluation of GALEN methods for
      mapping of follow-up categories in the domain of thoracic surgery to an existing
      classification of surgical procedures. The mapping of the aggregated levels or
      groups of thoracic procedures presents a genuine problem in relation to strict
      hierarchical classifications, since the follow-up categories do not necessarily
      fit in the pre-set structure of the classification. Experiences from modelling of
      the traditional classification and of the follow-up categories are reported, and
      an analysis of the results is presented along with a discussion of opportunities
      and potential problems and pitfalls when applying GALEN models and tools.

PMID- 10901275
TI  - Evaluations of the prescription order entry system for outpatient clinics by
      physicians in the 80 university hospitals in Japan.
AB  - We investigated the evaluations of the prescription order entry system by the
      physicians who are the direct users of this system. Questionnaires were sent to
      400 staff physicians of 80 medical school affiliated hospitals, out of which 76%
      responded. Among the respondents, 48 per cent are making use of the computerized
      outpatient prescription order entry system, and 52 per cent are not. The result
      shows 78% of the physicians are in favor of the prescription order entry system;
      the most dissatisfied opinion of the physicians toward the system was that the
      input took too much time thus reduced the communication with the patient.
      Physicians who are using the system seemed to favor the system more than the
      physicians who are not using it.

PMID- 10901276
TI  - Computer assisted information resources navigation.
AB  - In this paper, the design and development of Computer Assisted Information
      Resources Navigation (CAIRN) is discussed. CAIRN system is a medical information
      retrieval system that allows physicians and students to store full text medical
      information from any resource, organize and retrieve it. The most important
      feature of CAIRN is its capability to assist the user, physician, student etc. in
      selecting documents against a submitted query in Natural Language. The retrieved
      documents are presented in decreasing order according to their similarity to the
      submitted query. The nearest neighbour method is used. An alternative similarity
      measure based on a new calculation of the length of documents is proposed and
      some experimentation with it is discussed.

PMID- 10901277
TI  - Use of an artificial neural network (ANN) for classifying nursing care needed,
      using incomplete input data.
AB  - BACKGROUND: In German nursing insurance, the act of classifying the client into
      four categories of disability is based on legally defined distinct criteria. When
      classifying deceased persons it is often impossible to collect all the required
      information. PRIMARY OBJECTIVE: We aimed to determine the ability of an
      artificial neural network (ANN) to calculate the category of disability, to
      investigate the response of the ANN to input items of different nature, quantity
      and data quality, and to estimate the minimum number of training data required.
      RESEARCH DESIGN: The investigation was conducted as a retrospective observational
      study. METHODS AND PROCEDURES: The analysis was based on routine records of 14000
      adult clients of the nursing insurance. Several ANNs were trained, varying
      nature, number and quality of the input items as well as the size of the training
      data set. Each ANN's classification competence was tested on independent
      validation data, judging the ANN's conformance to the result of the individual
      expert assessment, using kappa statistics. MAIN RESULTS: Fed with all 30 input
      items available, the net classified 80% of cases correctly (weighted kappa =
      0.78). Using three input items, weighted kappa was 0.63. Severe misclassification
      (deviation by more than one category in either direction) ranged between 0.2%
      (all 30 input items) and 3.7% (3/30 items). The less complete the individual
      input items were, the less accurate was the net's estimate. A 20% rate of missing
      values was well tolerated. A training set comprising 500 cases was adequate.
      CONCLUSIONS: The input item set inherits redundancy. The ANN's ability to
      correctly respond to subsets of input items makes it a powerful tool in quality
      control. In the categorization of deceased persons when only an incomplete input
      item set is available, the ANN can achieve satisfactory results.

PMID- 10901278
TI  - Melatonin scavenges hydroxyl radical and protects isolated rat hearts from
      ischemic reperfusion injury.
AB  - During postischemic reperfusion, free radicals are produced and have deleterious
      effects in isolated rat hearts. We investigated whether melatonin (MEL) reduces
      the production of hydroxyl radical (*OH) in the effluent and aids in recovery of
      left ventricular (LV) function. Hearts were subjected to 30 min of ischemia
      followed by 30 min of reperfusion. Salicylic acid (SAL) was used as the probe for
      *OH, and its derivatives 2,5- and 2,3-dihydroxybenzoic acid (DHBA) were
      quantified using HPLC. In addition, thiobarbituric acid reactive substances
      (TBARS) in the myocardium was measured. Plateaus in the measurement of 2,5- and
      2,3-DHBA were seen from 3 to 8 min after reperfusion in each group. The group
      that received 100 microM MEL+ SAL had significantly reduced amounts of 2,5- and
      2,3-DHBA by multiple folds, compared to the SAL group. TBARS was significantly
      decreased in the 100 microM MEL group (1.20+/-0.36 vs 1.85+/-0.10 micromol/g of
      drug-free group, p<0.001). More importantly, the 100 microM MEL group
      significantly recovered in LV function (LV developed pressure, +dp/dt, and 
      dp/dt; 63.0%, 60.3%, and 59.4% in the 100 microM MEL group; 30.2%, 29.7%, and
      31.5% in the drug-free group, respectively; p<0.05). Duration of ventricular
      tachycardia or ventricular fibrillation significantly decreased in the 100 microM
      MEL group (100 microM MEL, 159+/-67 sec; drug-free, 1244+/-233 sec; p<0.05). As a
      result of scavenging *OH and reducing the extent of lipid peroxidation, MEL is an
      effective agent for protection against postischemic reperfusion injury.

PMID- 10901279
TI  - Comparison of physical dependence of ohmefentanyl stereoisomers in mice.
AB  - Stereo-structural difference of ohmefentanyl stereoisomers on analgesic action
      and receptor affinity has been studied. To assess the difference of ohmefentanyl
      stereoisomers in physical dependence, the potency of physical dependence was
      quantified by estimating the ED50 value of ohmefentanyl stereoisomers in the
      naloxone-precipitated jumping test in mice. Morphine was used to assess the
      method and as a drug of comparison. The results indicate that the degree of
      physical dependence of morphine can been quantified by estimating the ED50 value
      of morphine withdrawal jumping induced by naloxone. A significant difference was
      observed in withdrawal jumping ED50 values among ohmefentanyl stereoisomers. Of
      these isomers, F9202 and F9204 had similarly potent analgesic action, but very
      significant difference in naloxone precipitated withdrawal response. Dependent
      potency index of F9204 was 618-fold weaker than that of F9202. It is concluded
      that a stereo-structural difference in physical dependence is found to exist
      among ohmefentanyl stereoisomers. Compound F9204 displayed a strong analgesic
      action and weak physical dependent potency.

PMID- 10901280
TI  - Procyanidins in crataegus extract evoke endothelium-dependent vasorelaxation in
      rat aorta.
AB  - The extract of Crataegus, a mixture of flavonoids and procyanidins extracted from
      hawthorn, Crataegus oxyacantha, L. and C. monogyna Jacq., relaxed vascular tone
      or increased production of cyclic GMP in the rat aorta, but flavonoid components
      of Crataegus extract, hyperoside, rutin and vitexin, did not affect the vascular
      tone. The aim of the present study was to characterize the endothelium-dependent
      relaxation elicited by procyanidins fractionated from Crataegus extract in
      isolated rat aorta. Procyanidins caused endothelium-dependent relaxation which
      was associated with the production of cyclic GMP. Both responses to these
      procyanidins were inhibited by methylene blue or N(G)-nitro-L-arginine, but not
      by indomethacin. Relaxation in response to procyanidins was not affected by
      atropine, diphenhydramine, [D-Pro2,D-Trp7,9]substance P, propranolol, nifedipine,
      verapamil and glibenclamide, but were markedly reduced by tetraethylammonium.
      These findings showed that procyanidins in Crataegus extract may be responsible
      for the endothelium-dependent nitric oxide-mediated relaxation in isolated rat
      aorta, possibly via activation of tetraethylammonium-sensitive K+ channels.

PMID- 10901281
TI  - In vitro regulation of extracellular superoxide dismutase in sertoli cells.
AB  - Rat Sertoli and germ cells express extracellular superoxide dismutase (SOD(EX)),
      however, the relative level of SOD(EX) expressed by these cells was not known. We
      report herein germ cells consisting largely of spermatogonia, spermatocytes, and
      round spermatids expressed only one-third SOD(EX) as that of Sertoli cells when
      examined by semi-quantitative RT-PCR. While cocultures of germ cells with Sertoli
      cells failed to induce any changes in SOD(EX) expression possibly due to the
      limited number of cells that can be supported by the in vitro culture system
      dissimilar to the in vivo condition, incubation of total germ cell-conditioned
      medium with Sertoli cells was able to significantly inhibit Sertoli cell SOD(EX)
      expression dose-dependently suggesting a germ cell-derived soluble factor(s) may
      regulate SOD(EX) in the testis. On the other hand, cytokines such as TGF-beta1,
      beta-NGF, or FGF and steroid hormones such as estradiol-17beta, progesterone,
      testosterone, and DHT were unable to effect the expression of Sertoli cell
      SOD(EX). However, FSH at 100 ng/dish was able to induce a significant increase in
      Sertoli cell SOD(EX) expression. While cytokines, the known mediators of the
      inflammatory response, were unable to affect Sertoli cell SOD(EX) expression, the
      induction of generalized inflammation in vivo was able to cause a 2- to 2.5-fold
      increase in testicular SOD(EX) expression concomitant with a transient increase
      in the liver but not in the brain. Taken collectively, these results demonstrate
      that while SOD(EX) is an important antioxidant enzyme protecting the testis from
      reactive oxygen species, the mechanism(s) regulating its expression may involve
      an array of molecules and is a complicated cellular event.

PMID- 10901282
TI  - Oral N-acetyl-cysteome increases the production of anti HIV chemokines in
      peripheral blood mononuclear cells.
AB  - The C-C chemokines MIP-1alpha, MIP-1beta and RANTES are specific and powerful
      inhibitors of HIV infectivity. They appear to work by blocking the interaction of
      the virus with the receptor (CCR5). The latter is utilized as a coreceptor for
      cell penetration by macrophage-tropic (R5) HIV strains responsible for the
      majority of HIV transmissions. A natural high capability to release such
      chemokines has been proposed as a protection factor against HIV infection in
      exposed uninfected individuals. We report that oral administration of N-acetyl
      cysteine (NAC) to healthy volunteers increases the capability of their peripheral
      blood mononuclear cells (PBMC) to release such anti HIV chemokines upon
      stimulation. The data reported may explain at least in part the mechanism of
      action of NAC as an anti HIV therapeutic agent: By potentiating chemokine
      production NAC may decrease susceptibility to infection.

PMID- 10901283
TI  - Suppression of cytokine production and cell adhesion molecule expression in human
      monocytic cell line THP-1 by Tripterygium wilfordii polysaccharide moiety.
AB  - Extracts of the vine-like plant Tripterygium wilfordii (TW) have been widely used
      in China as an immunosuppressant and anti-inflammatory drug for the treatments of
      rheumatoid arthritis, lupus erythematosus and other inflammatory disorders. In
      this study the molecular mechanisms of action of three TW extracts (ethanol,
      aqueous, polysaccharide) on the expression of inflammatory cytokines and adhesion
      molecules were investigated by RT-PCR and immunofluorescence binding techniques.
      The lipopolysaccharide (LPS)-mediated stimulatory effects of tumor necrosis
      factor-alpha (TNF-alpha) cytokine production and cell adhesion molecule (CD11c,
      CD18, CD14, CD54) expression in human monocytic THP-1 cells were modulated by
      treatments of the TW extracts or tacrolimus (FK506). The TW polysaccharide moiety
      exhibited more profound immunosuppressive properties than the aqueous and ethanol
      extracts. Biochemical characterization of the polysaccharide moiety revealed a
      major molecular weight of 22 kDa (viz. PSP22). The PSP22 was found to be a
      potential immunosuppressant that manifests the necessary immunomodulating
      properties.

PMID- 10901284
TI  - Metformin treatment enhances insulin-stimulated glucose transport in skeletal
      muscle of Sprague-Dawley rats.
AB  - Although the glucose-lowering properties of metformin are well-established, its
      effects on glucose metabolism in skeletal muscle have not been clearly defined.
      We tested the effects of metformin in young adult male Sprague-Dawley rats, which
      have a documented reduced response to insulin in skeletal muscle. Rats were
      treated with metformin for 20 days (320 mg/kg/day) in the drinking water. During
      this period, metformin completely prevented the increase in food intake and
      decreased adiposity by 30%. Metformin also reduced insulin secretion by 37%
      following an intra-peritoneal injection of glucose. Finally, metformin enhanced
      transport of [3H]-2-deoxyglucose in isolated strips of soleus muscle. Metformin
      substantially increased insulin-stimulated transport, while having no effect on
      basal transport. In control rats, a maximal concentration of insulin stimulated
      transport 77% above basal. In metformin-treated rats, insulin stimulated
      transport 206% above basal. We conclude that in the Sprague-Dawley rat model,
      metformin causes a significant increase in insulin-responsiveness.

PMID- 10901285
TI  - Identification of human cytochrome P450 isoforms involved in the 7-hydroxylation
      of chlorpromazine by human liver microsomes.
AB  - Studies to identify the cytochrome P450 (CYP) isoform(s) involved in
      chlorpromazine 7-hydroxylation were performed using human liver microsomes and
      cDNA-expressed human CYPs. The kinetics of chlorpromazine 7-hydroxylation in
      human liver microsomes showed a simple Michaelis-Menten behavior. The apparent Km
      and Vmax values were 3.4+/-1.0 microM and 200.5+/-83.7 pmol/min/mg, respectively.
      The chlorpromazine 7-hydroxylase activity in human liver microsomes showed good
      correlations with desipramine 2-hydroxylase activity (r = 0.763, p < 0.05), a
      marker activity for CYP2D6, and phenacetin O-deethylase activity (r = 0.638, p <
      0.05), a marker activity for CYP1A2. Quinidine (an inhibitor of CYP2D6)
      completely inhibited while alpha-naphthoflavone (an inhibitor of CYP1A2)
      marginally inhibited the chlorpromazine 7-hydroxylase activity in a human liver
      microsomal sample showing high CYP2D6 activity. On the other hand, alpha
      naphthoflavone inhibited the chlorpromazine 7-hydroxylase activity to 55-65% of
      control in a human liver microsomal sample showing low CYP2D6 activity. Among
      eleven cDNA-expressed CYPs studied, CYP2D6 and CYP1A2 exhibited significant
      activity for the chlorpromazine 7-hydroxylation. The Km values for the
      chlorpromazine 7-hydroxylation of both cDNA-expressed CYP2D6 and CYP1A2 were in
      agreement with the Km values of human liver microsomes. These results suggest
      that chlorpromazine 7-hydroxylation is catalyzed mainly by CYP2D6 and partially
      by CYP1A2.

PMID- 10901286
TI  - Nonsteroidal anti-inflammatory drugs and phenols glucuronidation in Caco-2 cells:
      identification of the UDP-glucuronosyltransferases UGT1A6, 1A3 and 2B7.
AB  - Glucuronidation of phenols (1-naphthol, 4-methylumbelliferone) and nonsteroidal
      anti-inflammatory drugs (NSAIDs) such as ketoprofen, naproxen and carprofen was
      investigated in human colon carcinoma Caco-2 cell clones. Glucuronidation of
      these substances was highly effective in microsomes of the clones PD-7 and TC-7,
      but much lower in the PF-11 clone. The activity increased up to a maximum after
      21 days of culture. RT-PCR experiments indicated that the PD-7 and TC-7 clones
      expressed the UDP-glucuronosyltransferase (UGT) isoforms UGT1A6, UGT1A3 and
      UGT2B7, which could account for the glucuronidation of phenols and carboxylic
      acids observed. Beta-naphthoflavone stimulated by 2-fold the enzyme activity
      toward 1-naphthol in PD-7 and TC-7 clones, but not in PF-11 cells. This increase
      was parallel to that of the UGT1A6 mRNA level. Glucuronidation of ketoprofen was
      also sensitive to the inducing effect of beta-naphthoflavone. Actinomycin D and
      cycloheximide did not affect the induction of UGT1A6 by beta-naphthoflavone, but
      suppressed that of ketoprofen UGT. The UGT1A3 mRNA content was enhanced by beta
      naphthoflavone; by contrast, that of UGT2B7 was insensitive to the inducer. In
      conclusion, several UGT isoforms of both families 1 and 2, which glucuronidate
      phenols and carboxylic NSAIDs, have been identified in Caco-2 cells. They are
      differently sensitive to beta-naphthoflavone.

PMID- 10901287
TI  - Preference for vegetable oils in the two-bottle choice test in mice.
AB  - We evaluated in mice their preference for different vegetable oils using the two
      bottle choice test. Mice showed preference for all vegetable oils (at 1%
      concentration in emulsion) tested, including corn oil, canola oil, and mixed
      vegetable oil, compared to a control fluid without oil. Mice also significantly
      preferred highly palatable sucrose solutions (5-20%) in this test. One percent
      corn oil was selected to the same extent as were these sucrose solutions.
      Mixtures of 1% corn oil and several concentrations of sucrose were preferentially
      selected as compared to corn oil or sucrose alone. The concentration-response
      curves of oil-sucrose mixtures vs sucrose (0.5-20% concentrations) were similar
      to those of sucrose vs control solutions. These results suggest that 1% corn oil
      and sucrose at the concentrations tested did not affect each other's preference.
      Chronic intake of 20% sucrose solution, but not 100% corn oil, changed the
      preference for lower concentrations of each, and both induced remarkable
      increases in body weight of mice. In conclusion, we showed that mice preferred
      vegetable oils, and this preference compared favorably with highly palatable
      sucrose solutions and was not changed by chronic intake of corn oil.

PMID- 10901288
TI  - Synthesis and in vitro/in vivo evaluation of novel oral N-alkyl- and N,N-dialkyl
      carbamate esters of entacapone.
AB  - Entacapone has a relatively low oral bioavailability which may, in part, be due
      to its low aqueous solubility at low pH and/or its hydrophilic character at
      neutral pH. Various novel N-alkyl and N,N-dialkyl carbamate esters of entacapone
      were synthesized as possible prodrugs of entacapone in order to increase its
      aqueous solubility at an acidic pH and to increase its lipophilicity at neutral
      pH. Oral bioavailability of entacapone and selected carbamate esters were
      investigated in rats. Both N-alkyl and N,N-dialkyl carbamate esters were
      relatively stable against chemical hydrolysis at pH 7.4 (t1/2 = 14.9-20.7 h), but
      hydrolyzed rapidly (t1/2 = 0.8-2.7 h) in human serum. However, in contrast to N
      alkyl carbamates, N,N-dialkyl carbamates did not release entacapone in in vitro
      enzymatic hydrolysis (human serum) studies. N-Alkyl carbamates, 2a-c, showed
      increased aqueous solubility at pH 7.4, of which 2a and 2c also show increased
      aqueous solubility at pH 5.0, compared to entacapone. In addition to increased
      aqueous solubility, 2c showed increased lipophilicity at pH 7.4. However, two N
      alkyl carbamates of entacapone did not increase the oral bioavailability of the
      parent drug in rats. Thus, it can be concluded that the relatively low
      lipophilicity of entacapone is not the cause of its low bioavailability.

PMID- 10901289
TI  - The enantioselectivity of enzymes involved in current antiviral therapy using
      nucleoside analogues: a new strategy?
AB  - This review is primarily intended for synthetic bio-organic chemists and
      enzymologists who are interested in new strategies in the design of virus
      inhibitors. It is an attempt to assess the importance of the enzymatic properties
      of L-nucleosides and their analogues, particularly those that are active against
      viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV),
      herpes simplex virus (HSV), etc. Only data obtained with purified enzymes have
      been considered and discussed. The examined enzymes include nucleoside- or
      nucleotide-phosphorylating enzymes, catabolic enzymes, viral target enzymes and
      cellular polymerases. The enantioselectivities of these enzymes were determined
      from existing data and are significant only when a sufficient number of
      enantiomeric pairs of substrates could be examined. The reported data emphasize
      the weak enantioselectivities of cellular or viral nucleoside kinases and some
      viral DNA polymerases. Thus, cellular deoxycytidine kinase has a considerably
      relaxed enantioselectivity with respect to a large number of nucleosides or their
      analogues, and it occupies a strategic position in the intracellular activation
      of the compounds. Similarly, HIV-1 reverse transcriptase often has a relatively
      weak enantioselectivity and can be inhibited by the 5-triphosphates of a large
      series of L-nucleosides and analogues. In contrast, degradation enzymes, such as
      adenosine or cytidine deaminases, generally demonstrate strict
      enantioselectivities favouring D-enantiomers and are used by chemists in
      asymmetric syntheses. The weak enantioselectivities of some enzymes involved in
      nucleoside metabolism are more or less pronounced, and one enantiomer or the
      other is favoured depending on the substrate. This suggests that the low
      enantioselectivity is fortuitous and does not result from evolutionary pressure,
      since these enzymes do not create or modify asymmetric centres in substrates. The
      combined enantioselectivities of the enzymes examined in this review strongly
      suggest that the field of L-nucleosides and their analogues should be
      systematically explored in the search for new virus inhibitors.

PMID- 10901290
TI  - Synthesis and enantioselectivity of the antiviral effects of (R,Z)-,(S,Z)
      methylenecyclopropane analogues of purine nucleosides and phosphoralaninate
      prodrugs: influence of heterocyclic base, type of virus and host cells.
AB  - A series of R and S enantiomers of 2-aminopurine methylenecyclopropane analogues
      of nucleosides was synthesized. Two diastereoisomeric lipophilic phosphate
      prodrugs derived from R and S enantiomers of 2,6-diaminopurine analogue were also
      prepared. Enantioselectivity (diastereoselectivity in case of prodrugs) of in
      vitro antiviral effects was investigated with human and murine cytomegalovirus
      (HCMV and MCMV, respectively), herpes simplex virus types 1 and 2 (HSV-1 and HSV
      2, respectively), human immunodeficiency virus type 1 (HIV-1), hepatitis B virus
      (HBV), Epstein-Barr virus (EBV) and varicella zoster virus (VZV). Strong
      differences in enantioselectivity were found between the R and S enantiomers of
      adenine analogue and enantiomeric 2-aminopurine analogues. Thus, the enantiomers
      of adenine analogue were equipotent against HCMV but not MCMV, where the S
      enantiomer is strongly preferred. The same S preference was found throughout the
      2-aminopurine series for both HCMV and MCMV. In contrast, R-synadenol in HIV-1
      assays was the best agent, whereas the S enantiomers of moderately effective 2
      amino-6-cyclopropylamino and 2-amino-6-methoxypurine analogues were preferred.
      Little enantiomeric preference was found for R and S enantiomers of synadenol and
      the corresponding enantiomers of 2,6-diaminopurine analogue against HBV. A mixed
      pattern of enantioselectivity was observed for EBV depending on the type of host
      cells and assay. Against VZV, the R and S enantiomers of adenine analogue were
      equipotent or almost equipotent, but throughout the series of 2-aminopurine
      analogues a distinct preference for the S enantiomers was found. The
      stereoselectivity pattern of both diastereoisomeric prodrugs mostly followed
      enantioselectivity of the parent analogues. The varying enantioselectivities in
      the series of purine methylenecyclopropane analogues are probably a consequence
      of differences in the mechanisms of action in different virus/host cell systems.

PMID- 10901291
TI  - Pharmacokinetics of bis(t-butyl-SATE)-AZTMP, a bispivaloylthioethyl prodrug for
      intracellular delivery of zidovudine monophosphate, in mice.
AB  - The pharmacokinetics of a bispivaloylthioethyl prodrug of zidovudine
      monophosphate (AZTMP), bis(t-butyl-SATE)-AZTMP, and intracellular conversion of
      the prodrug to AZTMP were characterized following intravenous (i.v.) and oral
      (p.o.) administration of the prodrug to mice. Concentrations of bis(t-butyl-SATE)
      AZTMP, AZTMP and zidovudine (AZT) in blood, red blood cells, plasma, brain and
      lymph nodes were determined by HPLC. Following i.v. administration of bis(t-butyl
      SATE)-AZTMP, concentrations of the prodrug declined rapidly with low levels of
      the prodrug detected until 4 h. Both bis(t-butyl-SATE)-AZTMP and AZTMP were
      detected in brain 3 min after dosing. AZTMP was found in both plasma and
      peripheral red blood cells, peaking at approximately 30 min and remaining
      detectable until 2 h. No AZTMP was detected in lymph nodes. Compared to the
      pharmacokinetics of AZT following its i.v. administration, i.v. administration of
      bis(t-butyl-SATE)-AZTMP produced lower peak concentrations of AZT in plasma,
      peripheral red blood cells, brain and lymph nodes. However, terminal half-lives
      of AZT were significantly prolonged following administration of the prodrug.
      Following p.o. administration of bis(t-butyl-SATE)-AZTMP, neither the prodrug nor
      AZTMP were detectable in whole blood. The conversion of AZT from bis(t-butyl
      SATE)-AZTMP in plasma and peripheral red blood cells following p.o administration
      was 12.1% of that following i.v. administration of the prodrug. Bis(t-butyl-SATE)
      AZTMP demonstrated promising potential for intracellular delivery of AZTMP. The
      prodrug also prolonged the retention of AZT in mice, and particularly increased
      delivery of AZT to the lymphatic and central nervous systems.

PMID- 10901292
TI  - In vitro anti-HIV-1 activity of sn-2-substituted 1-O-octadecyl-sn-glycero-3
      phosphonoformate analogues and synergy with zidovudine.
AB  - Monoalkyl ether lipid analogues of foscarnet (phosphonoformate, PFA) exhibit
      substantially greater in vitro antiviral activity than unmodified PFA against
      human immunodeficiency virus type 1 (HIV-1). Our previous studies indicate that
      the length of the alkyl chain must be 14-22 carbons for optimal antiviral
      activity. To further evaluate the structure-activity relationship, we prepared 1
      O-octadecyl-sn-glycerol analogues of PFA with various substitutions at the sn-2
      position of glycerol and determined the effect of structure on in vitro antiviral
      activity and selectivity against HIV-1 in MT-2 and CD4-expressing HeLa cells (HT4
      6C). We also studied combinations of zidovudine with PFA, 1-O-octadecyl-2-O
      methyl-sn-glycero-3-PFA, or 1-O-octadecyl-sn-glycero-3-PFA and calculated their
      combination index values against HIV-1 in HT4-6C cells. Alkyl substitutions of
      one to four carbons at the sn-2 position of glycerol showed optimal antiviral
      activity. Both alkyl ether lipid analogues were strongly synergistic with
      zidovudine over a wide range of drug ratios and concentrations. 1-O-octadecyl-sn
      glycerol analogues of PFA have selective antiviral properties and warrant further
      evaluation as potential antiretroviral drugs.

PMID- 10901293
TI  - Thienothiadiazine 2,2-dioxide acyclonucleosides: synthesis and antiviral
      activity.
AB  - The synthesis of acyclonucleosides derived from thieno[3,2-c] and thieno[2,3
      c][1,2,6]thiadiazine 2,2-dioxides was achieved following the silylation method.
      Lipase-mediated methodology was employed for deprotection of the acyclic
      moieties. The antiviral effects were determined against a broad spectrum of
      viruses, including cytomegalovirus (CMV) and varicella zoster virus (VZV). Only
      minor antiviral activity against VZV was observed for those acyclonucleosides
      carrying a benzyl group.

PMID- 10901294
TI  - Antiviral and virucidal activities against arenaviruses of zinc-finger active
      compounds.
AB  - Fifteen antiretroviral Zn-finger active compounds with diverse chemical
      structures, including azoic compounds, hydrazide derivatives, disulphide-based
      reagents and others were screened in vitro against Junin virus (JUNV), the
      aetiological agent of Argentine haemorrhagic fever, by a virus yield inhibition
      assay in Vero cells. Cytotoxicity was evaluated simultaneously by the MTT method.
      Of the compounds, three were totally inactive as antivirals, nine presented
      moderate anti JUNV-activity and three were truly active with EC50 (effective
      concentration 50%) values in the range 6.5-9.3 microM and with selectivity
      indices greater than 10. The most active inhibitors, named NSC20625, 3-7 and 2
      71, demonstrated a broad range of action against arenaviruses, including several
      attenuated and pathogenic strains of JUNV as well as the antigenically related
      Tacaribe virus (TACV) and Pichinde virus (PICV). The direct treatment of JUNV and
      TACV virions with the compounds showed two types of behaviour: the aromatic
      disulphide NSC20625 was a very potent virucidal agent, whereas the other two
      compounds exhibited moderate or negligible virus-inactivating properties.

PMID- 10901295
TI  - Effect of intramuscularly injected polyprenols on influenza virus infection in
      mice.
AB  - This study demonstrates the possibility of achieving a prophylactic effect by
      intramuscular injection of Abies sibirica polyprenols for the control of
      influenza virus infection in mice. One of the five polyprenol preparations
      tested, preparation N1, which had the lowest hydrophilic-lipophilic balance
      (8.6), produced a significant protective effect when injected in a dose of 2000
      microg/mouse 2 days before aerosol infection of mice with influenza virus. A
      moderate protective effect was also observed using a second preparation,
      designated N2. One day after aerosol infection, animals pre-treated with 2000
      microg doses of the polyprenol preparations or Hanks' solution showed no
      difference in the level of interferon accumulation in the lungs. Three days after
      injection of preparation N2 and N1, a significant decrease in spleen and thymus
      weights was, observed in the mice. One day after injection of these preparations,
      the number of lymphocytes in the bronchoalveolar tract of the mice exceeded
      almost twice that seen in mice treated with placebo. After 3 days, relative and
      absolute numbers of macrophages decreased, whereas those of lymphocytes increased
      significantly. Three days after the administration of preparations N1 and N2,
      macrophages became approximately twice as active in absorbing zymozan granules.
      Preparation N1 affected the system of superoxide radical anion production to a
      greater extent than preparation N2. The production of radical anions by the
      macrophages of the bronchoalveolar tract in the mice, 1 day after intramuscular
      injection of preparation N1, was significantly higher than that seen on day 3 and
      that induced by preparation N2 1 and 3 days after injection. These data indicate
      that emulsions of polyprenols that have relatively low hydrophilic-lipophilic
      balance, inhibit influenza virus infection in mice through a modulation of the
      host immune response.

PMID- 10901296
TI  - Characterization of anticancer agents by their growth inhibitory activity and
      relationships to mechanism of action and structure.
AB  - An analysis of the growth inhibitory potency of 122 anticancer agents available
      from the National Cancer Institute anticancer drug screen is presented. Methods
      of singular value decomposition (SVD) were applied to determine the matrix of
      distances between all compounds. These SVD-derived dissimilarity distances were
      used to cluster compounds that exhibit similar tumor growth inhibitory activity
      patterns against 60 human cancer cell lines. Cluster analysis divides the 122
      standard agents into 25 statistically distinct groups. The first eight groups
      include structurally diverse compounds with reactive functionalities that act as
      DNA-damaging agents while the remaining 17 groups include compounds that inhibit
      nucleic acid biosynthesis and mitosis. Examination of the average activity
      patterns across the 60 tumor cell lines reveals unique 'fingerprints' associated
      with each group. A diverse set of structural features are observed for compounds
      within these groups, with frequent occurrences of strong within-group structural
      similarities. Clustering of cell types by their response to the 122 anticancer
      agents divides the 60 cell types into 21 groups. The strongest within-panel
      groupings were found for the renal, leukemia and ovarian cell panels. These
      results contribute to the basis for comparisons between log(GI(50)) screening
      patterns of the 122 anticancer agents and additional tested compounds.

PMID- 10901297
TI  - Synthesis and antitumor cytotoxicity evaluation of pyrido[4,3,2-de]quinolines and
      isoquinolino[6,5,4,3-cde]quinolines.
AB  - A series of novel pyrido[4,3,2-de]quinoline and isoquinolino[6,5,4,3-cde]
      quinoline compounds was synthesized and evaluated for cytotoxicity in the
      National Cancer Institute developmental therapeutics program. The tricyclic
      compound 7 was synthesized by the cyclization of 3,4-diamino-1,2dimethoxybenzene
      with diethyl 1,3-acetonedicarboxylate. Oxidation of monochloropyrido[4,3,2
      de]quinoline 8 selectively produced 2,3-diketopyrido[4,3,2-de]quinoline 9 as deep
      violet crystals. Compound 9, when treated with acetone or acetophenone, affords
      the tetracyclic isoquinolino[6,5,4,3-cde]quinolines 13 and 14, respectively. 2,3
      Diketopyrido[4,3,2-de]quinolines 9 and 10 exhibit higher cytotoxic potency than
      isoquinolino[6,5,4,3-cdelquinolines 13, 14, 15 and 16. Compound 9 selectively
      affects the cell growth against leukemia CCRF-CEM and HL-60 cell lines, the non
      small cell lung cancer HOP-92 cell line, and breast cancer MDA-MB231/ ATCC and
      MDA-MB- 435 cell lines with GI(50) values of <2.0 microM. Modification of
      compound 9 with an ester group at the N-1 position afforded compound 10, which
      exhibits a wide spectrum of anticancer activities with a mean graph midpoint
      value of 1.8 microM against the 60 cancer cell lines.

PMID- 10901298
TI  - Biological properties of 5,11-dimethyl-6H-pyrido[3,2-b]carbazoles: a new class of
      potent antitumour drugs.
AB  - Thirteen 5,11-dimethyl-6H-pyrido[3,2-b]carbazoles, structurally related to the
      antitumour drug ellipticine, were tested for their cytotoxicity against the L1210
      murine leukaemia cell line and their antitumour activity against both leukaemias
      and solid tumours. Most of them showed an interesting antitumour activity against
      L1210 leukaemia, 4-hydroxy-9-chloro-2,3, 5,11-tetramethyl-6H-pyrido[3,2
      b]carbazole displaying a high antitumour activity against L1210 and P388
      leukaemias, B16 melanoma and M5076 sarcoma. Despite promising cytotoxic activity,
      4-ethoxy-5,11-dimethyl-6H-pyrido-[3,2-b]carbazole had no antitumour activity. The
      ability of four drugs to induce strand breaks in DNA was studied using the single
      cell gel electrophoresis assay (comet assay). Most of the molecules induced DNA
      breaks that were totally or partially repaired after 1 h. The effects of these
      compounds on the L1210 cell cycle were tested as well as their abilities to
      induce apoptosis in these cells. Three of them induced a G2/M blockade, without
      any obvious evidence of apoptosis. The other compound, 4-ethoxy-5,11-dimethyl-6H
      pyrido[3,2b]carbazole, did not lead to phase-specific blockade, but was a strong
      inductor of apoptosis in L1210 cells.

PMID- 10901299
TI  - Synthesis of new homochiral bispyrrolidines as potential DNA cross-linking
      antitumour agents.
AB  - We are seeking to develop more effective bifunctional alkylating agents as
      antitumour agents. We previously synthesized conformationally restricted nitrogen
      mustards containing one piperidine ring, then bispiperidine derivatives were
      designed and prepared with varying lengths of carbon chain between the two rings
      and structure-activity relationships in these systems were studied. A
      bispiperidine with the shortest bridge of two carbon atoms was the most reactive
      bifunctional alkylating agent. In order to extend this work and investigate the
      effects of a change in the size of the heterocyclic systems, new bispyrrolidine
      salts 17-23 with chloromethyl groups at the 2-positions and a bridge between the
      two nitrogen atoms of 2-8 carbon atoms were synthesized from L-proline so that
      only the LL-enantiomers were produced. The free bases were designed to be
      bifunctional alkylating agents via aziridinium ion formation with different
      distances between the two alkylating sites. All of the bispyrrolidines were
      efficient cross-linkers of naked DNA apart from those with three-carbon (18) and
      four-carbon (19) bridges, in contrast to the results with the bispiperidines. A
      piperazine derivative 24 with two potential alkylating sites was also shown to be
      an efficient cross-linker, as was an alicyclic compound 25 with six carbon atoms
      between the two alkylating sites. Compounds 26 and 30 with an extra carbon atom
      between the nitrogen and the leaving group were not cross-linkers, as expected if
      aziridinium ion formation is crucial for cross-linking ability. The preformed
      aziridine 27 with a further alkylating site was an efficient cross-linker.
      Compounds 28-29 with only one potential alkylating centre were not cross-linkers
      of DNA. None of the compounds, however, produced significant cytotoxicity in
      human tumour cells in vitro.

PMID- 10901300
TI  - Novobiocin-induced VP-16 accumulation and MRP expression in human leukemia and
      ovarian carcinoma cells.
AB  - We have previously reported that novobiocin potentiates the cytotoxic activity of
      etoposide (VP-16) and teniposide (VM-26) in a number of experimental tumor cell
      lines by inhibition of the efflux of the epipodophyllotoxins by an ATP-requiring
      transporter. In leukemia cells from 12/19 patients and in ovarian carcinoma cells
      from 2/4 patients, novobiocin, in a concentration range of 150-1000 microM,
      increased the intracellular accumulation of VP-16 by 30-250% by inhibiting its
      efflux. Novobiocin did not significantly increase the intracellular concentration
      of VP-16 in human mononuclear bone marrow cells from two individuals with normal
      bone marrow, suggesting that it might be possible to selectively modulate the
      intracellular accumulation of the epipodophyllotoxin in tumor cells relative to
      normal hematopoietic tissue. Previous findings from our laboratory have provided
      evidence that the membrane transporter for VP-16 which is inhibited by novobiocin
      is distinct from the P-glycoprotein. The expression of MRP, measured by
      immunoblotting, was variable in novobiocin-responsive and non-responsive leukemia
      cells, indicating that no direct relationship existed between the modulatory
      activity of novobiocin on the transport of VP-16 and the expression of the MRP
      gene. The findings indicate that the novobiocin-sensitive VP-16 transporter is
      (i) present in high frequency in leukemia and ovarian carcinoma cells, and (ii)
      probably not the P-glycoprotein or MRP.

PMID- 10901301
TI  - The interaction of chalcones with tubulin.
AB  - The chalcone 3,4,3',4',5'-pentamethoxychalcone is a potent cytotoxic agent. A
      series of chalcones and (E)-4-(4'-hydroxyphenyl)but-3-en-2-one were prepared and
      assessed for their ability to inhibit cell growth in vitro. The cytotoxicity
      correlates with their ability to bind to tubulin as measured by
      immunofluorescence, cell cycle analysis and disruption of microtubule assembly.
      Some of the chalcones were shown to bind to the type II oestrogen receptor.

PMID- 10901302
TI  - Photosensitizing properties of palladium-tetraphenylporphycene on cultured tumour
      cells.
AB  - In this study we describe photokilling properties and effects on the mitotic
      index (MI) of cultured HeLa cells induced by palladium(II)-tetraphenylporphycene
      (PdTPP(0)). The drug was synthesized by refluxing tetraphenylporphycene (TPP(0))
      and PdCl2 in dimethylformamide, followed by evaporation and purification by
      chromatography. Cells were treated with different concentrations of PdTPPo
      incorporated into dipalmitoylphosphatidylcholine liposomes, and red light
      irradiation (lambda > 600 nm) was performed at 21 mW/cm2. No dark toxicity was
      found when the drug was applied under our experimental conditions. Using lethal
      (LD(100)) treatments, cells showed the immediate occurrence of bubbles on the
      plasma membrane, whereas homogeneous nuclear condensation and loss of cytoplasm
      appeared 3-24 h later. An increased MI was found 6-8 h after sublethal LD(25) and
      LD(40) treatments as well as a high proportion of abnormal metaphases with
      altered spindle microtubules. Chromatin condensation and fragmentation were
      observed 8 h after LD(75) treatments. These results show that in comparison with
      TPP(0), the new sensitizer PdTPPo has more efficient photokilling properties
      which could be very valuable for the photodynamic therapy of cancer.

PMID- 10901303
TI  - In vitro characterization of the anticancer activity of membrane-active cationic
      peptides. I. Peptide-mediated cytotoxicity and peptide-enhanced cytotoxic
      activity of doxorubicin against wild-type and p-glycoprotein over-expressing
      tumor cell lines.
AB  - Cationic amphipathic peptides, such as the defensins and cecropins, induce cell
      death in prokaryotic and eukaryotic cells by increasing membrane permeability.
      Increased permeability may lead to cell lysis or, alternatively, may produce
      subtle changes in the membrane's barrier function that promote cell death. The in
      vitro cytotoxic and lytic activity of short mammalian-derived extended-helical
      cationic peptides and insect-derived alpha-helical peptides was measured in this
      study with the objective of establishing the anticancer potential of these
      agents. Two specific aims were addressed: (i) to assess the activity of peptides
      against non-malignant cells (sheep erythrocytes and human umbilical vein
      endothelial cells) versus tumor cells; and (ii) to characterize the cytotoxic
      activity using multidrug-resistant tumor cell lines in the presence and absence
      of the anthracycline doxorubicin. Cell lysis assays demonstrated that the lytic
      activity of the peptides tested was 2->50 times more cytotoxic to tumor cells
      than to non-malignant cells. Further, the cytotoxic activity of these peptides
      was equivalent when tested against sensitive and multidrug-resistant cell lines.
      In addition to their inherent cytotoxic activity, these membrane-active peptides
      can also augment the in vitro cytotoxic activity of doxorubicin against multidrug
      resistant tumor cells.

PMID- 10901304
TI  - The use of ketamine sedation.

PMID- 10901305
TI  - Ketamine sedation for the reduction of children's fractures in the emergency
      department.
AB  - BACKGROUND: There recently has been a resurgence in the utilization of ketamine,
      a unique anesthetic, for emergency-department procedures requiring sedation. The
      purpose of the present study was to examine the safety and efficacy of ketamine
      for sedation in the treatment of children's fractures in the emergency
      department. METHODS: One hundred and fourteen children (average age, 5.3 years;
      range, twelve months to ten years and ten months) who underwent closed reduction
      of an isolated fracture or dislocation in the emergency department at a level-I
      trauma center were prospectively evaluated. Ketamine hydrochloride was
      administered intravenously (at a dose of two milligrams per kilogram of body
      weight) in ninety-nine of the patients and intramuscularly (at a dose of four
      milligrams per kilogram of body weight) in the other fifteen. A board-certified
      emergency physician skilled in airway management supervised administration of the
      anesthetic, and the patients were monitored by a registered nurse. Any pain
      during the reduction was rated by the orthopaedic surgeon treating the patient
      according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS).
      RESULTS: The average time from intravenous administration of ketamine to
      manipulation of the fracture or dislocation was one minute and thirty-six seconds
      (range, twenty seconds to five minutes), and the average time from intramuscular
      administration to manipulation was four minutes and forty-two seconds (range,
      sixty seconds to fifteen minutes). The average score according to the Children's
      Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points),
      reflecting minimal or no pain during fracture reduction. Adequate fracture
      reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight)
      of the sixty-nine parents present during the reduction were pleased with the
      sedation and would allow it to be used again in a similar situation. Patency of
      the airway and independent respiration were maintained in all of the patients.
      Blood pressure and heart rate remained stable. Minor side effects included nausea
      (thirteen patients), emesis (eight of the thirteen patients with nausea),
      clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction
      (one patient). No long-term sequelae were noted, and no patients had
      hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly
      provided adequate sedation to effectively facilitate the reduction of children's
      fractures in the emergency department at our institution. Ketamine should only be
      used in an environment such as the emergency department, where proper one-on-one
      monitoring is used and board-certified physicians skilled in airway management
      are directly involved in the care of the patient.

PMID- 10901306
TI  - Operative results of the inferior capsular shift procedure for multidirectional
      instability of the shoulder.
AB  - BACKGROUND: Neer and Foster previously described the inferior capsular shift
      procedure for treating multidirectional instability of the shoulder and reported
      preliminary results that were quite satisfactory. The purpose of our study was to
      perform a longer-term follow-up evaluation of the efficacy of the inferior
      capsular shift procedure for treating multidirectional instability of the
      shoulder. METHODS: An inferior capsular shift procedure was used to treat
      multidirectional instability of the shoulder in forty-nine patients (fifty-two
      shoulders). All patients had failed to respond to an exercise program. In this
      series, the operative approach (anterior or posterior) was based on the major
      direction of the instability, as determined by the preoperative history and
      physical examination and as verified by examination with the patient under
      anesthesia. In all of the patients, the inferior capsular shift was the primary
      attempt at operative stabilization. The repair consisted of a lateral-side (or
      humeral-side) shift of the capsule to reduce capsular redundancy and, when
      necessary, a reattachment of the avulsed labrum to the anteroinferior aspect of
      the glenoid. RESULTS: A redundant capsular pouch was seen in all of the shoulders
      in this series. In addition, detachment of the anteroinferior aspect of the
      labrum was found in ten shoulders and an anterior fracture of the glenoid rim was
      seen in two shoulders. At an average of sixty-one months (range, twenty-four to
      132 months), results were available for forty-nine shoulders (forty-six
      patients). Thirty shoulders (61 percent) had an excellent overall result, sixteen
      (33 percent) had a good result, one (2 percent) had a fair result, and two (4
      percent) had a poor result. Forty-seven (96 percent) of the forty-nine shoulders
      remained stable at the time of follow-up. Two of the thirty-four shoulders that
      had been repaired through an anterior approach began to subluxate
      anteroinferiorly again. None of the fifteen shoulders that had been repaired
      through a posterior approach had recurrent instability. Full function, including
      the ability to perform strenuous manual tasks, was restored to forty-five
      shoulders (92 percent). A return to sports was possible after thirty-one (86
      percent) of the thirty-six procedures done in athletes; however, a return to the
      premorbid level of participation was possible after only twenty-five (69 percent)
      of the thirty-six procedures. CONCLUSIONS: The results in this series demonstrate
      the efficacy and the durability of the results of the inferior capsular shift
      procedure for the treatment of shoulders with multidirectional instability. The
      procedure directly addresses the major pathological feature - a redundant joint
      capsule. Similar results were seen with either an anterior or a posterior
      approach, and we continue to approach shoulders with multidirectional instability
      on the side of greatest instability. A postoperative brace was reserved for
      patients in whom a posterior approach had been used or in whom an anterior
      approach had involved extensive posterior capsular dissection (ten of the thirty
      four shoulders treated with the anterior approach).

PMID- 10901307
TI  - A meta-analysis of thromboembolic prophylaxis following elective total hip
      arthroplasty.
AB  - BACKGROUND: Although several agents have been shown to reduce the risk of
      thromboembolic disease, there is no clear preference for thromboembolic
      prophylaxis in elective total hip arthroplasty. The purpose of this study was to
      define the efficacy and safety of the agents that are currently used for
      prophylaxis against deep venous thrombosis -- namely, low-molecular-weight
      heparin, warfarin, aspirin, low-dose heparin, and pneumatic compression. METHODS:
      A Medline search identified all randomized, controlled trials, published from
      January 1966 to May 1998, that compared the use of one of the prophylactic agents
      with the use of any other agent or a placebo in patients undergoing elective
      total hip arthroplasty. For a study to be included in our analysis, bilateral
      venography had to have been performed to confirm the presence or absence of deep
      venous thrombosis. Fifty-two studies, in which 10,929 patients had been enrolled,
      met the inclusion criteria and were included in the analysis. The rates of
      distal, proximal, and total (distal and proximal) deep venous thrombosis;
      symptomatic and fatal pulmonary embolism; minor and major wound-bleeding
      complications; major non-wound bleeding complications; and total mortality were
      determined for each agent in each study. The absolute risk of each outcome was
      determined by dividing the number of events by the number of patients at risk. A
      general linear model with random effects was used to calculate the 95 percent
      confidence interval of risk. A crosstabs of study by outcome was performed to
      test homogeneity (ability to combine studies). The risk of each outcome was
      compared among agents and between each agent and the placebo. RESULTS: With
      prophylaxis, the risk of total (proximal and distal) deep venous thrombosis
      ranged from 17.7 percent (low-molecular-weight heparin) to 31.1 percent (low-dose
      heparin); the risk with prophylaxis with any agent was significantly lower than
      the risk with the placebo (48.5 percent) (p < 0.0001). The risk of proximal deep
      venous thrombosis was lowest with warfarin (6.3 percent) and low-molecular-weight
      heparin (7.7 percent), and again the risk with any prophylactic agent was
      significantly lower than the risk with the placebo (25.8 percent) (p < 0.0001).
      Compared with the risk with the placebo (1.51 percent), only warfarin (0.16
      percent), pneumatic compression (0.26 percent), and low-molecular-weight heparin
      (0.36 percent) were associated with a significantly lower risk of symptomatic
      pulmonary embolism. There were no significant differences among agents with
      regard to the risk of fatal pulmonary embolism or of mortality with any cause.
      The risk of minor wound-bleeding was significantly higher with low-molecular
      weight heparin (8.9 percent) and low-dose heparin (7.6 percent) than it was with
      the placebo (2.2 percent) (p < 0.05). Compared with the risk with the placebo
      (0.28 percent), only low-dose heparin was associated with a significantly higher
      risk of major wound-bleeding (2.56 percent) and total major bleeding (3.46
      percent) (p < 0.0001). CONCLUSIONS: The best prophylactic agent in terms of both
      efficacy and safety was warfarin, followed by pneumatic compression, and the
      least effective and safe was low-dose heparin. Warfarin provided the lowest risk
      of both proximal deep venous thrombosis and symptomatic pulmonary embolism.
      However, there were no identifiable significant differences in the rates of fatal
      pulmonary embolism or death among the agents. Significant risks of minor and
      major bleeding complications were observed with greater frequency with certain
      prophylactic agents, particularly low-molecular-weight heparin (minor bleeding)
      and low-dose heparin (both major and minor bleeding).

PMID- 10901309
TI  - Efficacy of postoperative blood salvage following total hip arthroplasty in
      patients with and without deposited autologous units.
AB  - BACKGROUND: Patients undergoing total hip replacement routinely receive
      perioperative blood transfusions, increasing their risk of blood-borne disease,
      isoimmunization, anaphylactic reaction, and hemolytic reaction. The purpose of
      this retrospective, case-control study was to evaluate the effect of
      postoperative blood salvage on the need for allogeneic transfusion following
      total hip replacement. METHODS: We reviewed the medical records of ninety
      consecutive patients who, during a twelve-month period, had undergone unilateral,
      elective total hip replacement that included use of a postoperative blood salvage
      device. For comparison, we reviewed the medical records of ninety consecutive
      patients who had undergone total hip replacement without postoperative blood
      salvage. Overall, 156 patients had complete medical records and were included in
      the study. RESULTS: Eight (10 percent) of the patients who had been treated with
      a drain and seventeen (23 percent) of the patients who had been treated without a
      drain received allogeneic transfusions. Of the nineteen patients who had not
      deposited autologous blood, all six without postoperative blood salvage required
      allogeneic transfusion. With control for other variables in the model, regression
      analysis showed a significantly increased risk of allogeneic transfusion among
      patients who had undergone total hip replacement without postoperative blood
      salvage (p = 0.0028) and without having predonated autologous units (p = 0.0001).
      CONCLUSIONS: Despite a limited sample size, the study results showed that
      postoperative blood salvage significantly reduced the risk of allogeneic
      transfusion among patients managed with total hip replacement, whether or not
      they had deposited autologous blood (p < 0.0001). With control for donated units,
      age, gender, preoperative hematocrit, intraoperative blood loss, and cementless
      technique, patients who were treated without postoperative blood salvage were
      approximately ten times more likely to require allogeneic transfusion than were
      patients who had a drain.

PMID- 10901308
TI  - Arthrodesis as an early alternative to nonoperative management of charcot
      arthropathy of the diabetic foot.
AB  - BACKGROUND: This study was performed to evaluate the use of arthrodesis of the
      tarsal-metatarsal area for the treatment of Eichenholtz stage-I Charcot
      arthropathy in patients with diabetes. Currently, the standard treatment of stage
      I Charcot arthropathy is the application of a non-weight-bearing total-contact
      cast. Although this treatment can be effective for allowing a patient to walk
      without undergoing an operation, a nonunion or malunion may still result. The
      subsequent deformities may lead to complications, including ulceration of the
      foot and the need for operative intervention. Recently, a group of patients who
      had had early operative intervention for a variety of reasons provided us with
      the opportunity to objectively evaluate the effects of such treatment. This
      analysis provided valuable information about whether this treatment is a
      reasonable alternative to current nonoperative approaches. METHODS: Between
      January 1991 and December 1996, fourteen patients had an operation because of
      Eichenholtz stage-I diabetic neuropathy. The classification of the disease as
      Eichenholtz stage I (the developmental stage) was based on radiographic evidence
      of varying degrees of articular-surface and subchondral-bone resorption and
      fragmentation as well as joint subluxation or dislocation without evidence of
      coalescence or callus formation. The operative procedure consisted of extensive
      debridement, open reduction, and internal fixation of the tarsal-metatarsal
      region with autologous bone graft. Postoperative treatment consisted of
      immobilization of the limb in a non-weight-bearing cast for a minimum of six
      weeks. All of the patients returned for a final follow-up visit at a mean of
      forty-one months (range, 25.3 to 77.3 months) postoperatively, at which time
      clinical and radiographic evaluations as well as gait analysis (with measurement
      of plantar pressures) were performed. The gait-analysis data was compared with
      similar data from a group of fourteen patients with diabetic neuropathy who had
      had a below-the-knee amputation and with that from a group of fourteen patients
      with diabetic neuropathy who had no history of plantar ulceration. RESULTS: All
      of the arthrodesis procedures were successful. Clinically, none of the patients
      had immediate or long-term complications postoperatively. No patient reported
      ulceration after the operation. The mean time to assisted weight-bearing was 10
      +/- 3.3 weeks (range, six to fifteen weeks), the mean time to unassisted weight
      bearing was 15 +/- 8.8 weeks (range, eight to thirty-four weeks), and the mean
      time to return to the use of regular shoes was 27 +/- 14.4 weeks (range, twelve
      to sixty weeks). All of the patients regained the level of walking ability that
      they had had prior to the arthropathy. The calculated confidence intervals
      revealed no differences between the arthrodesis group and either of the two
      comparison groups with regard to the time-distance gait parameters of velocity,
      cadence, and stride length or with regard to the minimum, maximum, and total
      range of motion of each of the joints. In contrast to able-bodied subjects, all
      three groups showed a reduction in sagittal-plane ankle motion that was primarily
      related to loss of plantar flexion. The first metatarsal, great toe, and heel
      showed the highest peak plantar pressures, with little difference among the
      groups. CONCLUSIONS: To our knowledge, the present study is the first to
      demonstrate the potential for early operative treatment to restore anatomical
      alignment and improve function of diabetic patients with stage-I Charcot
      arthropathy.

PMID- 10901310
TI  - Reliability, validity, and responsiveness of the lower extremity measure for
      patients with a hip fracture.
AB  - BACKGROUND: The purpose of this study was to determine whether currently
      published outcome measures of physical function would be suitable for use for
      older adults with a hip fracture. The measures that were considered were the
      Musculoskeletal Function Assessment (MFA) Instrument, the Older Americans'
      Resources and Services (OARS) Multidimensional Functional Assessment
      Questionnaire physical function subscale, the Toronto Extremity Salvage Score
      (TESS), and the Short Form-36 (SF-36). Following suggestions by an expert panel
      and patient interviews, the MFA was not tested further. The TESS was modified and
      renamed the Lower Extremity Measure (LEM). METHODS: Forty-three community
      dwelling patients with a hip fracture completed the LEM, OARS, and SF-36 in the
      hospital so that the prefracture status could be obtained; they were then
      followed prospectively at six weeks and at six months. All patients were
      interviewed twice in the hospital to assess the reliability of the LEM
      (intraclass correlation coefficient = 0.85). To establish criterion validity, the
      measures were compared with the Timed Up and Go (TUG) test at six weeks. We
      tested a number of hypotheses to determine construct validity. RESULTS: Only the
      LEM scores were significantly correlated with the TUG scores (r = -0.53, p =
      0.03). The LEM scores were significantly correlated with the SF-36 subscale
      scores and the OARS scores. Patients with at least one comorbidity had a lower
      mean prefracture LEM score (90.0 +/- 9.7) than patients with no comorbidity (96.9
      +/- 8.1) (p = 0.02). Patients who had used no walking aids before the fracture
      had a higher mean prefracture LEM score than those who had used a cane (95.5 +/-
      5.8 compared with 85.5 +/- 12.7; p = 0.0007). Both the LEM and the SF-36 scores
      changed significantly between all of the time-periods (p < 0.05). Measures of
      responsiveness indicated that the LEM was the best measure for detecting changes
      in physical function. CONCLUSIONS: The LEM can detect clinically important
      changes in physical function over time in patients with a hip fracture and would
      be most useful for clinical trials or cohort studies. Orthopaedists who are
      currently utilizing the SF-36 can be reassured that the physical function
      subscale is a valid measure for patients with a hip fracture.

PMID- 10901312
TI  - The effect of surgery for rotator cuff disease on general health status. Results
      of a prospective trial.
AB  - BACKGROUND: Previous studies of the effect of rotator cuff surgery have
      concentrated on limb-specific or surgeon-based outcome criteria. We conducted a
      prospective trial to determine the effect of surgery for rotator cuff disease on
      general health status. METHODS: Seventy-one patients (fifty of whom were men and
      twenty-one of whom were women) with a mean age of 56.1 years were enrolled in the
      study. In addition to routine clinical and radiographic evaluation, all patients
      completed the Short Form-36 (SF-36) health-status questionnaire and five limb
      specific questionnaires preoperatively and at six, twelve, eighteen, and twenty
      four months postoperatively. All patients had a standard open acromioplasty and
      resection of the subacromial bursa. Thirty-one patients had repair of an
      associated rotator cuff tear. Sixty-seven patients (94 percent) completed the
      study; the remaining four patients were lost to follow-up. RESULTS: The
      preoperative SF-36 scores for physical function (60.6, p = 0.02), role function
      physical (20.8, p = 0.001), pain (38.6, p = 0.003), physical component summary
      (37.0, p = 0.001), and mental component summary (45.6, p = 0.02) were
      significantly decreased compared with normative data. The preoperative limb
      specific scores also were low. At the time of the most recent follow-up
      evaluation, there was improvement that approached or reached significance both in
      the limb-specific scores (p < or = 0.0026) and in the general-health-status
      scores for pain (p = 0.0001), role function-physical (p = 0.06), vitality (p =
      0.01), and physical component summary (p = 0.01). The presence of a rotator cuff
      tear had a significant negative effect on limb-specific scores both
      preoperatively (p = 0.04) and postoperatively (p = 0.05). Although operative
      treatment of rotator cuff disease led to improved scores, patients who had filed
      a Workers' Compensation claim had lower limb-specific and SF-36 scores both
      preoperatively (p = 0.02 and p = 0.01, respectively) and postoperatively (p =
      0.01 and p = 0.005, respectively). CONCLUSIONS: Surgery for chronic rotator cuff
      disease reliably and significantly improves general health status.

PMID- 10901311
TI  - Intrinsic resistance to chemotherapeutic agents in murine osteosarcoma cells.
AB  - BACKGROUND: There are two general categories of drug resistance: acquired and
      intrinsic. The mechanisms involved in acquired drug resistance have been
      extensively studied, and several mechanisms have been described. However, the
      mechanisms responsible for intrinsic drug resistance have not been elucidated, to
      our knowledge. The purpose of the present study was to investigate the
      cytological and biochemical differences between acquired and intrinsic drug
      resistance in osteosarcoma cells. METHODS: We previously isolated a clonal cell
      line (MOS/ADR1) to study acquired resistance in osteosarcoma by exposure of
      parental murine osteosarcoma cells (MOS) to doxorubicin. In the present study, we
      cloned a new, intrinsically resistant cell line (MOS/IR1) by single-cell culture
      of MOS cells and we investigated the differences in cell phenotype and the
      mechanisms of resistance in both of these resistant clones. RESULTS: The MOS/ADR1
      and MOS/IR1 cells were sevenfold and fivefold more resistant to doxorubicin than
      the parental murine osteosarcoma cells. Morphologically, the MOS/ADR1 cell line
      was composed of polygonal cells, whereas the MOS/IR1 cell line consisted of plump
      spindle cells with long cytoplasmic processes. The MOS/IR1 cells showed a much
      lower level of alkaline phosphatase activity than did the MOS/ ADR1 and MOS
      cells. There were no substantial differences in the cellular DNA content or the
      doubling time among these three lines. Overexpression of the P-glycoprotein
      involved in the function of an energy-dependent drug-efflux pump was detected in
      the MOS/ADR1 cells but not in the MOS/ IR1 cells. After the cells were incubated
      with doxorubicin for one hour, the two resistant lines had less accumulation of
      the drug than did the parent line (p < 0.05). The addition of a P-glycoprotein
      antagonist, verapamil, or the depletion of cellular adenosine triphosphate
      resulted in a marked increase in the accumulation of doxorubicin in the MOS/ADR1
      cells (p < 0.05) but not in the MOS/ IR1 cells. The MOS/ADR1 cells were found to
      exhibit cross-resistance only to substrates for P-glycoprotein (such as
      doxorubicin, vincristine, and etoposide), whereas the MOS/IR1 cells were
      resistant to all of the drugs studied (including cisplatin and methotrexate). The
      degree of drug resistance in the MOS/IR1 cells was found to be associated with
      the molecular weight of the drugs (p < 0.05). Permeabilization of the plasma
      membrane by saponin increased both the accumulation of doxorubicin (p < 0.05) and
      the cytotoxic activity of this drug in all lines, but the effects were most
      pronounced in the MOS/IR1 cells. CONCLUSIONS: Taken together, this data suggests
      that reduced drug accumulation in the MOS/IR1 cells may be due to the effect of
      decreased permeability of the plasma membrane on the transport of drugs from the
      extracellular environment into the cytosol of the cell and that this may be the
      mechanism responsible for intrinsic resistance to multiple drugs in the MOS/IR1
      cell line. CLINICAL RELEVANCE: Current drug treatment for human osteosarcoma may
      include multiple chemotherapeutic agents, such as doxorubicin, cisplatin, and
      methotrexate. These drugs exhibit different cytotoxic actions and, thus, the
      mechanisms of resistance to individual drugs vary. Clinical resistance to
      multidrug chemotherapy may be observed in tumors that recur after repetitive
      chemotherapy and in previously untreated tumors. In the former group, a tumor
      cell may express multidrug resistance by combining several different mechanisms
      due to its exposure to various drugs. In the latter group, however, this is not
      likely. Decreased intracellular drug accumulation due to reduced permeability of
      the plasma membrane, found in the MOS/IR1 cells, is one possible mechanism and
      may explain the intrinsic resistance to multidrug chemotherapy for the treatment
      of osteosarcoma. Further study regarding the resistance mechanism in the MOS/IR1
      cells may help to overcome the intrinsic drug resistance in oste

PMID- 10901313
TI  - Bristol-Myers Squibb/Zimmer award for distinguished achievement in orthopaedic
      research. Long-term follow-up of pediatric orthopaedic conditions. Natural
      history and outcomes of treatment.

PMID- 10901314
TI  - Arthroscopic treatment of anterior-inferior glenohumeral instability. Two to five
      year follow-up.
AB  - BACKGROUND: Previous studies on arthroscopic treatment of anterior-inferior
      glenohumeral instability have focused on the repair of lesions of the anterior
      inferior aspect of the labrum (Bankart lesions) and have demonstrated failure
      rates of as high as 50 percent. The current investigation supports the concept
      that anterior-inferior instability is associated with multiple lesions and that
      success rates can be increased by treating all of the lesions at the time of the
      operation. We present the results of arthroscopic treatment of anterior-inferior
      gleno-humeral instability after a minimum duration of followup of two years.
      METHODS: The study group consisted of fifty-three patients who had a mean age of
      thirty-two years (range, fifteen to fifty-eight years) at the time of the
      operation. There were forty-four male and nine female patients. The mean interval
      from the time of the operation to the final follow-up evaluation was thirty-three
      months (range, twenty-six to sixty-three months). The scores on the American
      Shoulder and Elbow Surgeons (ASES) Shoulder Index and the rating systems of
      Constant and Murley, Rowe et al., and the University of California at Los Angeles
      (UCLA) were recorded preoperatively and at the time of the final follow-up.
      RESULTS: Preoperatively, none of the patients had an overall rating of good or
      excellent according to the system of Rowe et al.; however, 92 percent (forty
      nine) of the fifty-three patients had a rating of good or excellent at the time
      of the final follow-up. The mean score improved from 45.5 points to 91.7 points
      on the ASES Shoulder Index, from 56.4 points to 91.8 points with the system of
      Constant and Murley, from 11.3 points to 91.9 points with the system of Rowe et
      al., and from 17.6 points to 32.0 points according to the UCLA Shoulder Score (p
      = 0.001 for all comparisons). The mean passive external rotation with the
      shoulder in 90 degrees of abduction measured 88.2 degrees. Thirty-four of thirty
      eight patients returned to their desired level of sports activity following the
      operation. Four patients who had persistent instability were considered to have
      had a failure of the index operation, and one of them had a second operative
      procedure. CONCLUSIONS: The results of the present study suggest that our
      technique of arthroscopic treatment of anterior-inferior glenohumeral instability
      is better than previous arthroscopic techniques and is equivalent to open repair.
      We believe that the improved rate of success demonstrated in the present study
      was the result of repair not only of the anterior-inferior (Bankart) lesion but
      also (where necessary) of inferior and superior labral tears. Additionally, soft
      tissue tension within the capsule and ligaments was corrected with use of a
      suture technique but was supplemented by laser thermal capsulorrhaphy in forty
      eight of the fifty-three shoulders. Rotator interval repair was considered a
      critical factor in fourteen of the fifty-three shoulders.

PMID- 10901315
TI  - Ultrasonography in developmental dysplasia of the hip.

PMID- 10901316
TI  - Academic longevity and attrition of full-time orthopaedic faculty members.

PMID- 10901317
TI  - Paternalism.
AB  - J. S. is a sixty-five-year-old man who was treated at another hospital with
      arthroscopic debridement of an infection at the site of a right total knee
      replacement and was placed on long-term intravenous antibiotics. He signed out of
      that hospital against medical advice. One month later, he presented at our
      hospital with recurrent sepsis of his knee. Knee aspiration yielded frank pus
      with a white blood-cell count of 80,000 cells per cubic millimeter. Gram-staining
      demonstrated gram-positive cocci. The patient was placed on intravenous
      antibiotics. The patient appeared cachectic, reporting a sixty-pound (27.2
      kilogram) weight loss over the past year. A metastatic workup, including a chest
      radiograph, an abdominal sonogram, prostate-specific antigen, a complete blood
      cell count, erythrocyte sedimentation rate, and a purified-protein-derivative
      skin test, was negative; however, an occult neoplasm could not be excluded. The
      patient displayed episodes of confusion, disorientation, and argumentative
      behavior. Medical and psychiatric consults did not determine whether this
      behavior was due to previous substance abuse or a primary psychiatric disorder.
      Nevertheless, psychiatrists at our institution determined that the patient lacked
      decisional capacity. Attempts were made to salvage the knee replacement, and the
      patient underwent an extensive surgical debridement of the knee with insertion of
      drains. He was placed on intravenous antibiotics. The plan was for the patient to
      be managed with long-term oral suppressive antibiotics. After treatment, the
      patient was transferred to a skilled-nursing facility. Psychiatrists at the
      nursing facility deemed the patient to have decisional capacity, and the patient
      was permitted to leave the facility. He was discharged without antibiotics.
      Several weeks later, he presented at our hospital with a grossly purulent knee.
      The orthopaedic options were reviewed with the patient and his brother. Removal
      of the components was recommended. The patient did not want to "lose" his knee
      replacement, and he refused surgical intervention. We did not believe that the
      infection could be either controlled or eradicated with the components in place.

PMID- 10901318
TI  - Value of recertification (I).

PMID- 10901319
TI  - Value of recertification (I).

PMID- 10901320
TI  - Value of recertification (I).

PMID- 10901321
TI  - Value of recertification (II).

PMID- 10901322
TI  - John Snow and modern-day environmental epidemiology.

PMID- 10901323
TI  - John Snow: the first hired gun?
AB  - The 1854 English cholera outbreak led to reform of Victorian public health
      legislation, including the Nuisances Removal and Diseases Prevention Act. The
      reforms threatened the closure of many factories whose fumes were considered
      hazardous to the public's health. The second witness to appear before the
      Parliamentary committee considering the reforms was Dr. John Snow. Snow testified
      on behalf of the manufacturers threatened by the reforms. He stated that the
      fumes from such establishments were not hazardous. He contended that the workers
      in these factories did not become ill as a result of their exposures, and
      therefore these fumes could not be a hazard to the general public's health. Snow
      also presented data from the 1854 cholera outbreak as the basis for his belief
      that epidemic diseases were transmitted by water, not air. Although the data
      concerned cholera, Snow extended the inference to all epidemic diseases. When the
      committee's report was published, The Lancet chastised Snow in a stinging
      editorial. Parliament subsequently revised the bill in favor of the manufacturers
      and passed it into law. The implications of this particular episode in the
      history of epidemiology are discussed.

PMID- 10901324
TI  - Invited commentary: the testimony of Dr. Snow.

PMID- 10901325
TI  - Soft-tissue sarcoma and non-Hodgkin's lymphoma clusters around a municipal solid
      waste incinerator with high dioxin emission levels.
AB  - Overall evidence from epidemiologic studies in the workplace suggests that dioxin
      is a human carcinogen, but whether low doses affect the general population
      remains to be determined. The authors examined the spatial distribution of soft
      tissue sarcomas and non-Hodgkin's lymphomas around a French municipal solid waste
      incinerator with high emission levels of dioxin (16.3 ng international toxic
      equivalency factor/m3). Not consistently associated with dioxin exposure,
      Hodgkin's disease served as the control cancer category. Clusters were identified
      from 1980 to 1995 in the area ("departement') of Doubs by applying a spatial scan
      statistic to 26 electoral wards. The most likely and highly significant clusters
      found were identical for soft-tissue sarcomas and non-Hodgkin's lymphomas and
      included the area around the municipal solid waste incinerator; standardized
      incidence ratios were 1.44 (observed number of cases = 45, focused test p value =
      0.004) and 1.27 (observed number of cases = 286, focused test p value = 0.00003),
      respectively. Conversely, Hodgkin's disease exhibited no specific spatial
      distribution. Confounding by socioeconomic status, urbanization, or patterns of
      medical referral seemed unlikely to explain the clusters. Although consistent,
      these findings should be confirmed by further investigation (e.g., a case-control
      study in which dioxins are measured in biologic tissues) before clusters of soft
      tissue sarcoma and non-Hodgkin's lymphoma are ascribed to dioxin released by the
      municipal solid waste incinerator.

PMID- 10901326
TI  - Extremely low-frequency magnetic fields and childhood acute lymphoblastic
      leukemia: an exploratory analysis of alternative exposure metrics.
AB  - Data collected by the National Cancer Institute-Children's Cancer Group were
      utilized to explore various metrics of magnetic field levels and risk of acute
      lymphoblastic leukemia (ALL) in children. Cases were aged 0-14 years, were
      diagnosed with ALL during 1989-1993, were registered with the Children's Cancer
      Group, and resided in one home for at least 70 percent of the 5 years immediately
      prior to diagnosis. Controls were identified by using random digit dialing and
      met the same residential requirements. With 30-second ("spot") measurements and
      components of the 24-hour measurement obtained in the subject's bedroom, metrics
      evaluated included measures of central tendency, peak exposures, threshold
      values, and measures of short-term temporal variability. Measures of central
      tendency and the threshold measures showed good-to-high correlation, but these
      metrics correlated less well with the others. Small increases in risk (ranging
      from 1.02 to 1.69 for subjects in the highest exposure category) were associated
      with some measures of central tendency, but peak exposures, threshold values,
      measures of short-term variability, and spot measurements demonstrated little
      association with risk of childhood ALL. In general, risk estimates were slightly
      higher for the nighttime (10 p.m.-6 a.m.) interval than for the corresponding 24
      hour period.

PMID- 10901327
TI  - Occupational exposure and lung cancer risk: a population-based case-referent
      study in Sweden.
AB  - This case-referent study investigated the lung cancer risk from occupational
      exposure to diesel exhaust, mixed motor exhaust, other combustion products,
      asbestos, metals, oil mist, and welding fumes. All cases of lung cancer in males
      aged 40-75 years among stable residents of Stockholm County, Sweden, were
      identified from 1985 to 1990. Referents were selected as a stratified (age,
      inclusion year) random sample. Information on lifetime occupational history,
      residency, and tobacco smoking was obtained from the study subjects or from next
      of kin. Response rates of 87% and 85% resulted in 1,042 cases and 2,364
      referents, respectively. Occupational exposures were assessed by an occupational
      hygienist who coded the intensity and probability of each exposure. Risk
      estimates were adjusted for tobacco smoking, other occupational exposures,
      residential radon, and environmental exposure to traffic-related air pollution.
      For the highest quartile of cumulative exposure versus no exposure, the relative
      risk was 1.63 (95% confidence interval (CI): 1.14, 2.33) for diesel exhaust, 1.60
      (95% CI: 1.09, 2.34) for combustion products, and 1.68 (95% CI: 1.15, 2.46) for
      asbestos. Dose-response analyses indicated an increase in lung cancer risk of 14%
      per fiber-year/ml for asbestos exposure. No increased risk was found for the
      other exposure factors. An overall attributable proportion of 9.5% (95% CI: 5.5,
      13.9) was estimated for lung cancer related to diesel exhaust, other combustion
      products, and asbestos.

PMID- 10901328
TI  - Electric blanket use and breast cancer in the Nurses' Health Study.
AB  - Electric and magnetic fields (EMFs) have been hypothesized to increase the risk
      of breast cancer, and electric blankets represent an important source of exposure
      to EMFs. The authors examined the relation between electric blanket use and
      invasive breast cancer in the Nurses' Health Study. On the biennial questionnaire
      in 1992, 87,497 women provided information on this exposure during three
      consecutive time periods. In a prospective analysis with 301,775 person-years of
      follow-up through 1996 (954 cases), the relative risk for any electric blanket
      use was not elevated (relative risk (RR) = 1.08, 95% confidence interval (CI):
      0.95, 1.24) after controlling for breast cancer risk factors. There was a weak
      association between breast cancer and electric blanket use at least 16 years
      before diagnosis and long-term use in age-adjusted analyses but not in
      multivariate models. In a retrospective analysis of 1,318,683 person-years of
      follow-up (2,426 cases), the multivariate relative risk associated with use
      before disease follow-up began was null (RR = 1.05, 95% CI: 0.95, 1.16). Similar
      results were obtained in analyses stratified by menopause and restricted to
      estrogen receptor-positive breast cancers. While 95% confidence intervals for
      these estimates did not exclude small risks, overall, results did not support an
      association between breast cancer risk and exposure to EMFs from electric
      blankets.

PMID- 10901329
TI  - Breast cancer risk associated with congeners of polychlorinated biphenyls.
AB  - Experimental studies show that hormonal and nonhormonal activities of
      polychlorinated biphenyls (PCBs) are structure dependent, suggesting that the
      breast cancer risk associated with PCBs may vary according to specific PCB
      congeners. In 1994-1997, the authors conducted a case-control study of
      Connecticut women to investigate whether breast cancer risk is associated with
      body burden of PCBs and varies by PCB congeners. A total of 304 breast cancer
      cases and 186 controls aged 40-79 years were recruited into the study. Fresh
      breast adipose tissue was analyzed for PCBs. The age- and lipid-adjusted
      geometric mean tissue levels of total PCBs were not significantly different (p =
      0.46) for the cases (478.6 parts per billion) and controls (494.1 parts per
      billion). The covariate-adjusted odds ratio was 0.7 (95% confidence interval:
      0.4, 1.1) for all study participants when the third tertile was compared with the
      lowest tertile. No individual congeners or groups of congeners were associated
      with a significantly increased risk of breast cancer. Further stratification by
      type of breast disease; menopausal, parity, and lactation status; and body size
      also showed no significant association with body levels of PCBs. These results
      suggest that environmental exposure to PCBs may not substantially affect breast
      cancer risk.

PMID- 10901330
TI  - Relation between aluminum concentrations in drinking water and Alzheimer's
      disease: an 8-year follow-up study.
AB  - To investigate the effect of aluminum and silica in drinking water on the risk of
      dementia and Alzheimer's disease, the authors analyzed data from a large
      prospective cohort (Paquid), including 3,777 subjects aged 65 years and over
      living at home in 75 civil parishes in Gironde and Dordogne in southwestern
      France in 1988-1989. The subjects were followed for up for 8 years with an active
      search for incident cases of dementia or Alzheimer's disease. Mean exposure to
      aluminum and silica in drinking water was estimated in each area. The sample
      studied included 2,698 nondemented subjects at baseline, for whom components of
      drinking water and covariates were available. A total of 253 incident cases of
      dementia (with 17 exposed to high levels of aluminum), including 182 Alzheimer's
      disease (with 13 exposed to high aluminum levels), were identified. The relative
      risk of dementia adjusted for age, gender, educational level, place of residence,
      and wine consumption was 1.99 (95 percent CI: 1.20, 3.28) for subjects exposed to
      an aluminum concentration greater than 0.1 mg/liter. This result was confirmed
      for Alzheimer's disease (adjusted relative risk = 2.14, 95 percent CI: 1.21,
      3.80). However, no dose-response relation was found. Inversely, the adjusted
      relative risk of dementia for subjects exposed to silica (> or = 11.25 mg/liter)
      was 0.74 (95 percent CI: 0.58, 0.96). These findings support the hypothesis that
      a high concentration of aluminum in drinking water may be a risk factor for
      Alzheimer's disease.

PMID- 10901331
TI  - Subject-domain approach to the study of air pollution effects on schoolchildren's
      illness absence.
AB  - In this paper, the authors propose a new statistical modeling technique, the
      subject-domain approach, which is theoretically proven to be equivalent to the
      time-domain approach in detecting an association between exposure and response
      with time trends. The authors use an empirical data set from a school absence
      monitoring study conducted during the 1994-1995 school year in Taiwan to
      demonstrate this subject-domain approach's application to environmental
      epidemiologic studies. Because the subject-domain models can control the
      influential personal confounding factors in the models, they show greater
      statistical power than the traditional time-domain approaches in determining the
      relation between air pollution and illness absences. The authors' models found
      that the schoolchildren's risks of illness absence were significantly related to
      acute exposures to nitrogen dioxide and nitrogen oxides with a 1-day lag (p <
      0.01) at levels below the World Health Organization's guidelines. By contrast,
      the authors could not detect significant associations between air pollution and
      schoolchildren's absenteeism using time-domain approaches. Such findings imply
      that the models built on subject domain may be a general solution to the problem
      of the ecologic fallacy, which is commonly encountered in environmental and
      social epidemiologic studies.

PMID- 10901332
TI  - Validity of annoyance scores for estimation of long term air pollution exposure
      in epidemiologic studies: the Swiss Study on Air Pollution and Lung Diseases in
      Adults (SAPALDIA).
AB  - In air pollution epidemiology, estimates of long term exposure are often based on
      measurements made at one fixed site monitor per area. This may lead to exposure
      misclassification. The present paper validates a questionnaire-based indicator of
      ambient air pollution levels and its applicability to assess their within-area
      variability. Within the framework of the SAPALDIA (Swiss Study on Air Pollution
      and Lung Diseases in Adults) cross-sectional study (1991), 9,651 participants
      reported their level of annoyance caused by air pollution on an 11-point scale.
      This subjective measure was compared with annual mean concentrations of
      particulate matter less than 10 microm in diameter (PM10) and nitrogen dioxide.
      The impact of individual factors on reported scores was evaluated. Nitrogen
      dioxide concentrations at home outdoors (measured in 1993), smoking, workplace
      dust exposure, and respiratory symptoms were found to be predictors of individual
      annoyance scores. Regression of population mean annoyance scores against annual
      mean PM10 and nitrogen dioxide concentrations (measured in 1993 and 1991,
      respectively) across areas showed a linear relation and strong correlations
      (r>0.85). Analysis within areas yielded consistent results. The observed
      associations between subjective and objective air pollution exposure estimates
      suggest that population mean scores, but not individual scores, may serve as a
      simple tool for grading air quality within areas. Reported annoyance due to air
      pollution should be considered an indicator for a complex environmental condition
      and thus might be used for evaluating the implementation of environmental
      policies.

PMID- 10901333
TI  - Measurement of low levels of arsenic exposure: a comparison of water and toenail
      concentrations.
AB  - A study was conducted to evaluate toenail arsenic concentrations as a biologic
      marker of drinking water arsenic exposure. Study subjects were controls in a US
      population-based case-control study of nonmelanoma skin cancer, randomly selected
      from drivers' license records (those < 65 years of age) and Medicare enrollment
      files (those > or = 65 years of age). Between 1994 and 1997, a total of 540
      controls were interviewed and toenail samples of sufficient weight were collected
      from 506 (93.7%) of these. Beginning in 1995, a sample of tap water was taken
      from the participants' homes; a total of 217 (98.6%) water samples were obtained
      from the 220 subjects interviewed. Arsenic determinations were made from toenail
      samples using neutron activation analysis. Water samples were analyzed using
      hydride-generation magnet sector inductively coupled mass spectrometry. Among 208
      subjects with both toenail and water measurements, the correlation (r) between
      water and nail arsenic was 0.65 (p < 0.001) among those with water arsenic
      concentrations of 1 microg/liter or higher and 0.08 (p = 0.31) among those with
      concentrations below 1 microg/liter (overall r = 0.46, p < 0.001). Our data
      suggest that toenail samples provide a useful biologic marker for quantifying low
      level arsenic exposure.

PMID- 10901334
TI  - External radiation exposure and mortality in a cohort of uranium processing
      workers.
AB  - In a study of 2,514 White male workers employed between 1942 and 1966 at a US
      uranium processing plant, mortality was compared with overall US mortality, and
      the relation between external ionizing radiation and cancer was evaluated.
      Through 1993, 1,013 deaths occurred. The mean cumulative dose was 47.8 mSv. The
      standardized mortality ratio (SMR) was 0.90 for all causes of death and 1.05 for
      all cancers. Many cancer sites had elevated SMRs. Among nonmalignant outcomes,
      the SMR for chronic nephritis was 1.88 (six deaths observed). An excess relative
      risk estimate of 10.5 per Sv (10 cases) was observed for kidney cancer; this may
      have resulted from chance, internal radiation, or chemical exposures not
      considered.

PMID- 10901335
TI  - The 7 habits of highly effective psychopharmacologists, part 3: sharpen the saw
      with selective choices of continuing medical education programs.
AB  - The highly effective psychopharmacologist will develop the habit of "sharpening
      the saw" by clever selection of unbiased and efficient CME programs that
      incorporate the most thoughtful applications of the principles of adult education
      to enhance retention rates after a single exposure.

PMID- 10901336
TI  - Partial response, nonresponse, and relapse with selective serotonin reuptake
      inhibitors in major depression: a survey of current "next-step" practices.
AB  - BACKGROUND: Many patients treated for major depression require more than one
      antidepressant trial to achieve or sustain response. However, the literature
      provides few treatment algorithms or effectiveness studies that empirically
      support "next-step" options available to clinicians. We conducted a survey of
      psychiatrists and other medical specialists who treat depression to ascertain
      what clinicians actually do when faced with patients who suboptimally respond to
      an adequate course of selective serotonin reuptake inhibitor (SSRI) therapy.
      METHOD: Attendees at a psychopharmacology course (N = 801) were queried about
      their top choices for antidepressant-treatment nonresponders: a minimal responder
      after 4 weeks of adequate SSRI treatment, a partial responder after 8 weeks of
      adequate SSRI therapy, a nonresponder after 8 weeks of adequate SSRI therapy, and
      a relapser on long-term SSRI maintenance therapy. Choices included raising the
      dose, augmenting or combining with another agent, switching to a second SSRI. or
      switching to a non-SSRI agent. RESULTS: 432 (54%) of the surveys were returned.
      Raising the dose was the most frequently reported next-step strategy for a
      patient with minimal response after 4 weeks of adequate SSRI therapy, partial
      response after 8 weeks of adequate SSRI therapy, and relapse on long-term SSRI
      therapy. Switching to a non-SSRI agent was the most frequently chosen option for
      nonresponders to an adequate trial of SSRI therapy. CONCLUSION: Our findings
      suggest that clinicians select different next-step strategies when patients are
      nonresponders versus when patients are partial responders or relapsers.

PMID- 10901337
TI  - Prior benzodiazepine exposure and benzodiazepine treatment outcome.
AB  - BACKGROUND: We examined discontinuation symptoms following brief benzodiazepine
      therapy (8 weeks) and intermittent benzodiazepine therapy (2 weeks with at least
      2 weeks without drug) and associations with prior benzodiazepine use. The
      hypothesis was that prior benzodiazepine use would predispose patients to more
      severe discontinuation symptoms. METHOD: Data were drawn from 3 double-blind,
      randomized, placebo-controlled, published treatment trials: alprazolam for
      patients with premenstrual syndrome (PMS) and diazepam and lorazepam for patients
      with generalized anxiety disorder (GAD). The PMS group provided prospective daily
      symptom ratings, which allowed ongoing investigation of effects of prior
      treatment. In the GAD groups, taper outcome was examined after 8 weeks of
      benzodiazepine therapy as a function of prior benzodiazepine use and as a
      function of time since last prior benzodiazepine use. Symptom scores were
      analyzed using t statistics in the PMS group and analysis of covariance with 8
      week scores as the covariate in the GAD groups. RESULTS: The PMS subjects
      reported no increase in symptom scores and no significant difference from placebo
      treated subjects during taper and discontinuation of alprazolam in the follicular
      phase of each treatment cycle. In the GAD trials, the results of treatment
      discontinuation did not differ significantly as a function of presence or absence
      of prior benzodiazepine use or as a function of time since last benzodiazepine
      use. CONCLUSION: These preliminary data fail to support the hypothesis that prior
      benzodiazepine use predisposes patients to more severe discontinuation symptoms
      when treatment is brief and doses are low.

PMID- 10901338
TI  - Low-dose amphetamine salts and adult attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: Effective treatments for attention-deficit/hyperactivity disorder
      (ADHD) in adults are still being defined. Pediatric studies have suggested that a
      mixed amphetamine salt product (Adderall) is safe and effective in the treatment
      of childhood forms of ADHD. Presently, there are no reports in the scientific
      literature concerning the safety and efficacy of Adderall in adults with ADHD,
      which is the focus of this study. METHOD: Twenty-four outpatients (mean age =
      33.3 years) with DSM-IV ADHD were administered Adderall in an open-label fashion,
      starting at 5 mg p.o. b.i.d., with titration according to clinical response,
      across a 16-week period. Relatives or spouses of each patient completed serial
      checklists (including the Copeland Symptom Checklist and the Brown Attention
      Deficit Disorder Scales). Prospectively collected data were analyzed
      retrospectively. RESULTS: Thirteen patients (54%) responded in a positive manner
      to Adderall, based on Clinical Global Impressions-Improvement scale scores. The
      mean end dose for responders was 10.77 mg/day (0.14 mg/kg/day). An intent-to
      treat analysis revealed a decrease in the mean Copeland score from 99.05 to 63.3
      (p < .001), while the mean Brown score dropped from 76.75 to 50.85 (p < .0001).
      Nine patients (38%) were poor responders or nonresponders to Adderall. Acute
      anxiety symptoms occurred in 4 of 7 patients with a comorbid anxiety diagnosis.
      CONCLUSION: Adderall may be an effective agent for the treatment of adult forms
      of ADHD, with positive responses occurring at relatively low doses, at least for
      some individuals. However, Adderall may precipitate anxiety in vulnerable
      individuals. Further study is required.

PMID- 10901340
TI  - A comparison of persons with early-versus late-onset panic attacks.
AB  - BACKGROUND: Although some evidence suggests a bimodal age at onset of panic
      attacks, the literature comparing subjects with early versus late onset is
      limited. Previous work suggests that people with late-onset panic attacks may
      have fewer panic symptoms and exhibit less avoidance. This study sought to
      compare late-onset panic attacks and early-onset panic attacks with regard to (I)
      comorbidity, (2) health care utilization, and (3) illness behaviors and coping.
      METHOD: This community-based study involved interviewing randomly selected adults
      for the presence of DSM-III-R panic attacks. If panic attacks were confirmed,
      subjects were asked questions concerning panic characteristics, psychiatric
      comorbidity, symptom perceptions, illness attitudes, coping, and family
      characteristics. Subjects reporting early-onset panic (panic onset < 50 years of
      age) were compared with those reporting late onset (onset > or = 50 years of
      age). Significant univariate analyses were controlled for differences in age,
      panic duration, and socioeconomic status by using analysis of covariance and
      logistic regression. RESULTS: Subjects with late-onset panic attacks (N = 9)
      utilized the mental health sector less, but were more likely to present to family
      physicians for their worst panic. Patients with late-onset panic felt that
      choking and numbness more strongly disrupted function, but felt less strongly
      that either depersonalization or sweating disrupted function. Subjects with late
      onset had fewer comorbid conditions and lower Symptom Checklist-90 scores. Late
      onset subjects also had less hypochondriasis and thanatophobia while coping less
      through avoidance or wishful thinking. CONCLUSION: Late-onset panic attacks are
      associated with less mental health utilization, lower levels of comorbidity, less
      hypochondriasis, and a greater number of positive coping behaviors.

PMID- 10901339
TI  - The Brief Psychiatric Rating Scale as an acute inpatient outcome measurement
      tool: a pilot study.
AB  - BACKGROUND: Recent guidelines for length of stay at psychiatric hospitals may
      have an unacceptable impact on patient outcome at discharge. A valid measurement
      tool is needed to evaluate significant patient change during brief
      hospitalization, typically 7 days, and to provide early prediction of unfavorable
      short-term outcome. This study examines the utility of the Brief Psychiatric
      Rating Scale (BPRS) as such a tool. METHOD: During a 2-month testing period, the
      BPRS was administered to 87 successive adults admitted to an acute general
      psychiatric inpatient unit at admission, 2 days, 7 days, and weekly thereafter
      until discharge. Total BPRS scores and 4 subscores were used in the data
      analysis, which included paired t tests and correlation analyses. RESULTS: Mean
      BPRS total scores demonstrate significant (p < .001) patient improvement at days
      2, 7, and 14 of the hospital stay. Changes in subscores and their relationship to
      eventual outcome vary across diagnostic groups. CONCLUSION: The BPRS appears to
      be a useful inpatient outcome measure since it is capable of demonstrating
      significant change during brief stays of 1 week or less. Subscale scores may
      provide more specific prediction of change and may help clarify outcome in
      individual patients who show insignificant change by total score.

PMID- 10901341
TI  - Childhood abuse and platelet tritiated-paroxetine binding in bulimia nervosa:
      implications of borderline personality disorder.
AB  - BACKGROUND: Co-occurrence of bulimia nervosa and borderline personality disorder
      has been attributed to shared factors, including childhood abuse and disturbances
      in central serotonin (5-hydroxytryptamine; 5-HT) mechanisms. To explore this
      notion, we conducted a controlled assessment of childhood abuse and 5-HT function
      in bulimics with and without borderline personality disorder. METHOD: Forty
      patients with bulimia nervosa, confirmed with the Eating Disorders Examination
      interview (14 with borderline personality disorder and 26 without), and 25 normal
      eater controls were assessed for clinical symptoms (eating disturbances, mood
      lability, impulsivity, and dissociation) and childhood sexual and physical abuse.
      We also conducted tests of platelet tritiated-paroxetine binding in blood samples
      from 27 of the bulimics (11 with borderline personality disorder and 16 without)
      and 16 of the controls. RESULTS: Relative to normal eaters, bulimics showed
      greater affective instability, overall impulsivity, and a history of physical
      abuse. However, borderline bulimics alone showed elevated motor impulsivity,
      dissociation, and rates of sexual abuse. Paroxetine-binding tests indicated no
      differences attributable to comorbid borderline personality disorder, instead
      linking bulimia nervosa with or without borderline personality disorder to
      substantially reduced 5-HT transporter density. CONCLUSION: Results suggest
      relatively autonomous pathologic entities: one, relevant to bulimia nervosa,
      being associated with abnormal 5-HT transporter function and affective
      instability, but relatively independent of childhood sexual abuse; another,
      relevant to borderline personality disorder, onto which sexual abuse,
      dissociative symptoms, and behavioral impulsivity converge. We propose that
      abnormal 5-HT function may, however, constitute one basis for the frequent co
      occurrence of bulimic and borderline disturbances.

PMID- 10901342
TI  - Effects of dextroamphetamine on depression and fatigue in men with HIV: a double
      blind, placebo-controlled trial.
AB  - BACKGROUND: This report documents findings from a small placebo-controlled trial
      of dextroamphetamine for depression and fatigue in men with the human
      immunodeficiency virus (HIV). Dextroamphetamine offers the potential for rapid
      onset of effect and activation properties, both of which are important to persons
      with medical illness and an uncertain, but limited, life expectancy. METHOD:
      Primary inclusion criteria included the presence of a DSM-IV depressive disorder,
      debilitating fatigue, and no history of dependence on stimulants. The study
      consisted of a 2-week randomized, placebo-controlled trial, with the blind
      maintained until week 8 for responders, followed by open treatment through the
      completion of 6 months. RESULTS: Of 23 men who entered the study, 22 completed
      the 2-week trial. Intent-to-treat analysis indicated that 73% of patients (8/11)
      randomly assigned to dextroamphetamine reported significant improvement in mood
      and energy, compared with 25% (3/12) among placebo patients (Fisher exact test, p
      < .05). Both clinician- and self-administered measures indicated significantly
      improved mood, energy, and quality of life among patients taking
      dextroamphetamine. There was no evidence of the development of tolerance of,
      abuse of, or dependence on the medication. CONCLUSION: These results suggest that
      dextroamphetamine is a potentially effective, fast-acting antidepressant
      treatment for HIV patients with depression and debilitating fatigue.

PMID- 10901344
TI  - WATCHERS: recognizing generalized anxiety disorder.

PMID- 10901343
TI  - Electrocardiographic abnormalities in patients treated with clozapine.
AB  - BACKGROUND: Cardiovascular side effects of clozapine are not uncommon, but few
      systematic studies of these effects have been performed. In this study, we
      reviewed data on the electrocardiographic (ECG) abnormalities in patients treated
      with clozapine. METHOD: Sixty-one patients treated with clozapine were selected
      from the Seoul National University Hospital Treatment-Resistant Schizophrenia
      Clinic. A retrospective chart review was conducted to identify ECG abnormalities
      and cardiovascular side effects. RESULTS: The prevalence of ECG abnormalities in
      patients who had been using antipsychotics other than clozapine was 13.6% at
      baseline, which increased significantly to 31.1% after commencement of clozapine
      treatment. Among the 53 patients without baseline ECG abnormalities, 13 showed
      new-onset ECG abnormalities after using clozapine. Normal ECG under previous
      antipsychotic medication reduced the risk of new-onset ECG abnormalities, whereas
      increased age was found to increase the risk. The occurrence of orthostatic
      hypotension or tachycardia was not related to the development of ECG
      abnormalities. Most of the newly developed abnormalities had little clinical
      significance, and they tended to occur during the initial phase of treatment. In
      10 patients, ECGs normalized despite the continued use of clozapine. Clozapine
      increased corrected QT interval (QTc) in a dose-dependent fashion; however, the
      clinical significance of this observation is uncertain. Pathologic prolongation
      of QTc was found to be rare. CONCLUSION: Although a substantial portion of
      patients treated with clozapine developed ECG abnormalities, most of the
      abnormalities were benign and did not hinder further treatment.

PMID- 10901345
TI  - Gold versus silver: the issue of functional versus symptomatic recovery in
      depression.

PMID- 10901346
TI  - SIADH with multiple antidepressants in a geriatric patient.

PMID- 10901347
TI  - Free drug fraction versus free drug concentration.

PMID- 10901348
TI  - Zolpidem-related delirium: a case report.

PMID- 10901349
TI  - Bupropion-tranylcypromine combination for treatment-refractory depression.

PMID- 10901350
TI  - Inappropriate masturbation and schizophrenia.

PMID- 10901352
TI  - Care for breast cancer: the adoption of newer clinical paradigms.

PMID- 10901351
TI  - Memory impairment in those who attempted suicide by benzodiazepine overdose.
AB  - BACKGROUND: A prospective study was conducted to investigate the presence of
      anterograde amnesia in those who attempted suicide by benzodiazepine overdose and
      to study the correlation with sedation. METHOD: In 43 patients who attempted
      suicide by taking benzodiazepines, memory was tested with a 15-word memory recall
      task. The immediate and delayed recall on the first day after admission (day 1)
      and 24 hours later (day 2) were rated. Each patient and the interviewer scored
      the patient's degree of sedation on a visual analogue scale. Patients also had to
      try to recognize, from photographs, the psychiatrist with whom they had spoken
      the day before. RESULTS: The ratings of immediate and delayed recall were
      significantly lower on day 1 than on day 2. Subjective ratings of sedation of the
      patients were not significantly higher than the ratings of the observer. Less
      than half of the patients recognized the psychiatrists and knew that they were
      the ones they had spoken to the day before. CONCLUSION: Anterograde amnesia is
      present in suicide attempters who take overdoses of benzodiazepines. The
      implications of this finding for the assessment of suicide attempters during
      admission are discussed.

PMID- 10901353
TI  - Referral of breast cancer patients to medical oncologists after initial surgical
      management.
AB  - BACKGROUND: Decisions to refer patients to other physicians for care or
      consultation are an important component of the provision of appropriate care for
      cancer patients. However, little is known about the referral process between
      specialists. OBJECTIVES: To examine the referral patterns of specialists to
      specialists and to understand why only some breast cancer patients receive a
      consultation with a medical oncologist. RESEARCH DESIGN: This study was conducted
      in a large metropolitan region from 1993 to 1995 using a 2-staged population
      based sampling strategy. One hundred seven physicians discussed 244 patient cases
      and their own knowledge, attitudes, and practices toward treatment and referral.
      RESULTS: Of the 244 patients, 87.7% were referred to an oncologist, and 10.2%
      were actually prescribed tamoxifen by their surgeons before they saw the
      oncologist. Surgeons who were less involved in making decisions about the type of
      adjuvant therapy the patients were to receive and who preferred the use of
      chemotherapy were significantly more likely to refer patients to oncologists.
      Patients who were older, unemployed, node negative, and had a better prognosis or
      preferred not to see an oncologist were significantly less likely to be referred.
      These 7 factors explained a total of 55% of the variation in surgeons' decisions
      to refer patients to an oncologist. CONCLUSIONS: Extramedical factors, such as
      surgeon and patient preferences and communication factors, play a strong role in
      the referral process. In this sample, most patients were referred to an
      oncologist. However, older, unemployed patients and patients whose medical
      features indicated a better long-term prognosis were most likely to be among the
      nonreferred group.

PMID- 10901354
TI  - The relationship of HMOs, health insurance, and delivery systems to breast cancer
      outcomes.
AB  - BACKGROUND: The current climate of anger and frustration with managed care has
      heightened interest in the quality of health care provided by managed-care plans,
      particularly health maintenance organizations (HMOs). This breast cancer outcomes
      study, investigating relationships of health insurance and delivery systems to
      stage at diagnosis, treatment selected, and survival, is based in a heavily
      penetrated, highly competitive HMO market. METHODS: Data for 1,788 residents of
      northern California younger than 65 years of age at diagnosis (1987-1993) were
      provided by a population-based cancer registry. Patient insurance included fee
      for-service (FFS), group-model HMO, nongroup HMO, publicly insured, and
      uninsured. Diagnosis and treatment occurred in 73 hospitals (large,
      medium/moderately small, or very small community, rural, teaching, or HMO-owned
      hospitals). Regression models examined relationships of insurance and hospital
      type to 3 outcomes (stage, treatment, and survival), controlling for age,
      ethnicity, education, neighborhood occupational class, and time period. RESULTS:
      Early diagnosis was as likely for group-model and nongroup-model HMO-insured
      patients as for the private FFS-insured patients. In 1987-1990, HMO-owned
      hospitals were leaders in treating 46% of early-stage breast cancers with breast
      conserving surgery plus radiation (BCS+); by 1991-1993, the most significant
      increases in BCS+ use occurred at teaching and large community hospitals.
      Survival of group-model HMO, nongroup-model HMO, and FFS patients was not
      significantly different. Publicly insured/uninsured patients had more stage
      III/IV disease (OR=2.01, P = 0.006) and greater all-cause mortality (risk ratio
      1.46, P = 0.015). CONCLUSIONS: Group-model and nongroup-model HMO patients are
      similar to FFS-insured patients in stage at diagnosis and survival outcomes.
      Treatment selection is related to hospital type rather than insurance coverage.

PMID- 10901355
TI  - Accuracy and completeness of Medicare claims data for surgical treatment of
      breast cancer.
AB  - BACKGROUND: Although a number of studies have used Medicare claims data to study
      trends and variations in breast cancer treatment, the accuracy and completeness
      of information on surgical treatment for breast cancer in the Medicare data have
      not been validated. OBJECTIVES: This study assessed the accuracy and completeness
      of Medicare claims data for breast cancer surgery to determine whether Medicare
      claims can serve as a source of data to augment information collected by cancer
      registries. METHODS: We used the Surveillance, Epidemiology and End Results
      (SEER) Cancer Registry-Medicare data and compared Medicare claims on surgery with
      the surgery recorded by the SEER registries for 23,709 women diagnosed with
      breast cancer at > or =65 years of age from 1991 through 1993. RESULTS: More than
      95% of women having mastectomies according to the Medicare data were confirmed by
      SEER. For breast-conserving surgery, 91% of cases were confirmed by SEER. The
      Medicare physician services claims and inpatient claims were approximately equal
      in accuracy on type of surgery. The Medicare outpatient claims were less accurate
      for breast-conserving surgery. In terms of completeness, when the 3 claims
      sources were combined, 94% of patients receiving breast cancer surgery according
      to SEER were identified by Medicare. CONCLUSIONS: The combined Medicare claims
      database, which includes the inpatient, outpatient, and physician service claims,
      provides valid information on surgical treatment among women known to have breast
      cancer. The claims are a rich source of data to augment the information collected
      by tumor registries and provide information that can be used to follow long-term
      outcomes of Medicare beneficiaries.

PMID- 10901356
TI  - Comparing the use of physician time and health care resources among patients
      speaking English, Spanish, and Russian.
AB  - BACKGROUND AND OBJECTIVES: The number of US residents with limited English
      proficiency (LEP) is 14 million and rising. The goal of this study was to
      estimate the effects of LEP on physician time and resource use. DESIGN: This was
      a prospective, observational study. SETTING AND SUBJECTS: The study included 285
      Medicaid patients speaking English (n = 112), Spanish (n = 62), or Russian (n =
      111) visiting the General Medicine and Family Practice Clinics at the UC Davis
      Medical Center in 1996-1997 (participation rate, 85%). Bilingual research
      assistants administered patient questionnaires, abstracted the medical record,
      and conducted detailed time and motion studies. MAIN OUTCOME MEASURES: We used
      seemingly unrelated regression models to evaluate the effect of language on visit
      time, controlling for patient demographics and health status, physician
      specialty, visit type, and resident involvement in care. We also estimated the
      effect of LEP on cross-sectional utilization of health care resources and
      adherence to follow-up with referral and testing appointments. RESULTS: The 3
      language groups differed significantly by age, education, and reason for visit
      but not gender, number of active medical conditions, physical functioning, or
      mental health. Physician visit time averaged 38+/-20 minutes (mean+/-SD).
      Compared with English-speaking patients and after multivariate adjustment,
      Spanish and Russian speakers averaged 9.1 and 5.6 additional minutes of physician
      time, respectively (P <0.05). The language effect was confined largely to follow
      up visits with resident physicians (house staff). Compared with English speakers,
      Russian speakers had more referrals (P = 0.003) and Spanish speakers were less
      likely to follow-up with recommended laboratory studies (P = 0.031). CONCLUSIONS:
      In these academic primary care clinics, some groups of patients using
      interpreters required more physician time than those proficient in English
      Additional reimbursement may be needed to ensure continued access and high
      quality care for this special population.

PMID- 10901357
TI  - A population-based analytical approach to assessing patterns, determinants, and
      outcomes of health care with application to ectopic pregnancy.
AB  - OBJECTIVE: Health care has variable features, specific determinants, and
      consequences on people's health that should be investigated in a population
      perspective. We present a population-based analytical approach to assessing
      patterns, determinants, and outcomes of health care. METHODS: The approach uses
      standard epidemiological methods for sample selection and analysis, as well as
      statistical methods concerning model fitting and validation strategy. It also
      uses psychometric methods allowing pattern identification: factor analysis,
      cluster analysis, and polytomous logistic regression to investigate the factors
      associated with identified patterns of care. The approach is illustrated with an
      application to ectopic pregnancy (EP). RESULTS: EP diagnostic and therapeutic
      procedures appeared to be closely related, suggesting 3 differentiated patterns
      of care. Predictors of these patterns were not only the clinical features and the
      woman's prior gynecological history but also center characteristics and location.
      These patterns were found to influence immediate and middle-term outcomes and
      risk of recurrence of EP. CONCLUSIONS: We illustrate the feasibility and
      profitability of a population-based analytical approach to identify patterns,
      determinants, and consequences of care. This approach could be used to analyze
      other pathological conditions and health care systems.

PMID- 10901358
TI  - National estimates of HIV-related symptom prevalence from the HIV Cost and
      Services Utilization Study.
AB  - OBJECTIVES: The objectives of this study were (1) to estimate the prevalence,
      bothersomeness, and variation of HIV-related symptoms in a nationally
      representative sample of HIV-infected adults receiving medical care and (2) to
      evaluate new aggregate measures of symptom frequency and bothersomeness. METHODS:
      Beginning in January 1996, 76% of a multistage national probability sample of
      4,042 HIV-infected adults receiving medical care were interviewed. Participants
      endorsed the presence and degree of bothersomeness of 14 HIV-related symptoms
      during the preceding 6 months. Sex-standardized symptom number and bothersomeness
      indices were constructed. After sampling weights were incorporated, symptom
      distributions were compared according to selected characteristics by analysis of
      variance and multiple linear regression modeling. RESULTS: Prevalence of specific
      symptoms in the reference population was as follows: fever/night sweats, 51.1%;
      diarrhea, 51%; nausea/anorexia, 49.8%; dysesthesias, 48.9%; severe headache,
      39.3%; weight loss, 37.1%; vaginal symptoms, 35.6% of women; sinus symptoms,
      34.8%; eye trouble, 32.4%; cough/dyspnea, 30.4%; thrush, 27.3%; rash, 24.3%; oral
      pain, 24.1%; and Kaposi's sarcoma, 4%. Aggregate measures were reliable
      (Cronbach's alpha > or =0.75) and demonstrated construct validity when compared
      with other measures of disease severity. After adjustment for CD4 count, both
      symptom number and bothersomeness varied significantly (P <0.05) by teaching
      status of care setting, exposure/risk group, educational achievement, sex, annual
      income, employment, and insurance category. However, the magnitude of variation
      was small. Symptoms were greatest in women and injection drug users, as well as
      in persons with lower educational levels, lower income, and Medicare enrollment
      or those who were followed up at teaching hospitals. CONCLUSIONS: The prevalence
      and bothersomeness of HIV-related symptoms are substantial and vary by setting of
      care and patient characteristics.

PMID- 10901359
TI  - Estimation of utilities for the effects of depression from the SF-12.
AB  - BACKGROUND: Utilities for health conditions, including major depressive disorder,
      have a theoretical relationship to health-related quality of life (HRQOL).
      Because of the complexity of utility measurement and the existence of large
      numbers of completed studies with HRQOL data but not utility data, it would be
      desirable to be able to estimate utilities from measurements of HRQOL. OBJECTIVE:
      The objective of this study was to estimate utility for remission in major
      depression by use of information on associated variation in Short Form 12 (SF-12)
      scores. DESIGN: A mapping function for SF-12 scores (based on a 6-health-state
      model with patient-weighted preferences) was applied to longitudinal data from a
      large naturalistic study to estimate changes in utilities. SUBJECTS: Preference
      ratings for states were performed in a convenience sample of depressed primary
      care patients (n = 140). Outcomes were evaluated in patients in the Course of
      Depression Study (n = 295) with a DSM III diagnosis of depression at the onset of
      the study. MEASURES: From clinical interview data, differences in utilities and
      global physical and mental health-related quality of life at 1- and 2-year follow
      up were compared for patients who did and did not experience remission as
      determined by the Course of Depression Interview. RESULTS: Remission of
      depression resulted in health status improvement, as measured by the SF-12,
      equivalent to a gain of 0.11 quality-adjusted life-years over 2 years.
      CONCLUSIONS: Utilities for changes in health status, associated with a clinical
      change in depression, can be modeled from the SF-12 scales, which results in
      utilities within the range of estimates described in the literature.

PMID- 10901360
TI  - Improving the precision of primary care physician self-report of antidepressant
      prescribing.
AB  - BACKGROUND: Methods to select physicians most likely to benefit from educational
      interventions to improve the outcome of depression have not been adequately
      developed. OBJECTIVE: The purpose of this study was to identify a combination of
      primary care provider (PCP) self-report questions to improve the precision of PCP
      estimates of actual antidepressant prescribing as a potential tool for PCP
      selection. METHODS: The total number of new and refill antidepressant
      prescriptions written by 124 PCPs and actually filled at pharmacies over a 2-year
      period were matched with telephone survey results of these PCPs completed before
      the 2-year period. Multiple regression techniques were used to identify a set of
      variables that improved upon PCPs' self-report of prescriptions. RESULTS: The
      mean for PCP-reported antidepressant prescriptions written in the last week was
      7.8 (+/-11.2). The average weekly prescriptions actually filled was 6.72 (+/
      5.65). Most survey variables were significantly correlated with antidepressant
      prescriptions. The final model included 6 variables that explained 52% of the
      variance in prescriptions. In addition to PCP-reported number of antidepressants
      prescribed, average number of primary care patients seen per week and number of
      patients covered by managed care were directly related to the volume of
      prescriptions. PCP age, percentage of patients referred immediately without
      treatment, and mental health services being too far away were inversely related.
      CONCLUSIONS: PCP self-reports on antidepressant prescribing are reasonably
      accurate proxies of actual prescribing. The precision of estimates of actual
      prescribing can be improved by considering practice structural and financial
      characteristics.

PMID- 10901361
TI  - Phase II study of S-1, a novel oral fluorophyrimidine derivative, in patients
      with metastatic colorectal carcinoma. S-1 Cooperative Colorectal Carcinoma Study
      Group.
AB  - This study set out to evaluate, in patients with metastatic colorectal carcinoma,
      the efficacy and toxicity of S-1, which contains tegafur, 5-chloro-2,4
      dihydroxypyridine (CDHP) and potassium oxonate, based on a biochemical modulation
      of 5-fluorouracil (5-FU) targeted at inhibition of dihydropyrimidine
      dehydrogenase (DPD). Sixty-three patients with measurable metastatic colorectal
      carcinoma were enrolled into the study. None of the patients had received prior
      chemotherapy except for adjuvant setting. S-1 was administered orally twice daily
      at a standard dose of 80 mg m(-2) day(-1) for 28 days followed by a 14-day rest.
      This agent is continued until disease progression, unaccepted toxicity, or
      patient refusal. Twenty-two (35%) of the 62 eligible patients achieved PR with a
      95% confidence interval of 25-48%. Five of the 10 patients with a history of
      adjuvant chemotherapy achieved partial remission. The median survival time was 12
      months. Major adverse reactions included myelosuppressive and gastrointestinal
      toxicities, though their incidence of grade 3 or 4 being 13% in neutropenia and
      less than 10% in the others. None of the 53 patients treated as outpatients
      required hospitalization due to adverse reactions: These results suggest that S-1
      achieves similar responses to those of infusional 5-FU plus leucovorin and shows
      the potential of another biochemical modulation with easily manageable toxicity.

PMID- 10901362
TI  - Phase I study of irinotecan and raltitrexed in patients with advanced
      gastrointestinal tract adenocarcinoma.
AB  - To determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD)
      of irinotecan and raltitrexed given as sequential short infusions every 3 weeks,
      33 patients with pretreated gastrointestinal adenocarcinoma (31 colorectal, 2
      oesophagogastric) entered this open label dose-escalation study. For the first
      five dose levels patients received irinotecan 175-350 mg m(-2) followed by
      raltitrexed 2.6 mg m(-2). Level VI was irinotecan 350 mg m(-2) plus raltitrexed
      3.0 mg m(-2), level VII was irinotecan 400 mg m(-2) plus raltitrexed 2.6 mg m(
      2); 261 courses were administered. Only one patient at dose levels I-V
      experienced DLT. At level VI, 5/12 patients experienced DLT: one had grade 3
      diarrhoea and lethargy, one had grade 4 diarrhoea and one had lethargy alone. Two
      others had lethargy caused by disease progression. There was no first-cycle
      neutropenia. At level VII, 3/6 patients experienced dose-limiting lethargy, one
      also had grade 3 diarrhoea. Dose intensity fell from over 90% for both drugs at
      level VI to 83% for irinotecan and 66% for raltitrexed at level VII. Lethargy was
      therefore the DLT, and level VII the MTD. Pharmacokinetic data showed no
      measurable drug interaction; 6/30 patients (20%) had objective responses. This
      combination is active with manageable toxicity. Recommended doses for further
      evaluation are irinotecan 350 mg m(-2) and raltitrexed 3.0 mg m(-2).

PMID- 10901363
TI  - Association of the I1307K APC mutation with hereditary and sporadic
      breast/ovarian cancer: more questions than answers.
AB  - The frequency of the APC I1307K mutation and its association with disease pattern
      was examined in 996 Ashkenazi women consisting of individuals with either
      sporadic (n = 382) or hereditary (n = 143) breast and/or ovarian cancer;
      asymptomatic BRCA1/2 mutation carriers (185delAG, 5382insC and 6174delT) (n= 53)
      and healthy controls (n= 418). The I1307K allele was equally distributed among
      women with sporadic (17/382; 4.6%) and inherited (10/143; 7%) breast and/or
      ovarian cancer irrespective of their being diagnosed before or after 42 years of
      age and among asymptomatic (7/53; 13.2%) and cancer manifesting BRCA1/2 carriers
      (10/143; 7%). Taken together, the prevalence of the I1307K allele was
      significantly higher in BRCA1/2 carriers compared to non-BRCA1/2 carriers
      (17/196; 8.7% and 40/800, 5%; respectively). The high prevalence of the I1307K
      allele among BRCA1/2 carriers is not associated with increased cancer risk but
      seems to be genetically connected because of Jewish ancestry.

PMID- 10901364
TI  - Osteopontin is required for full expression of the transformed phenotype by the
      ras oncogene.
AB  - The secreted phosphoprotein osteopontin (OPN) is strongly associated with the
      process of neoplastic transformation, based both on its pattern of expression in
      vivo and in vitro and on functional analyses. We have used 3T3 cells derived from
      wildtype and OPN-deficient mice and transformed by transfection with oncogenic
      ras to assess the role of OPN in transformation in vitro and in tumorigenesis in
      vivo. There was no effect of an absence of OPN on the ability of the cells to
      undergo immortalization or to form morphologically transformed foci following ras
      transfection. Wildtype and OPN-deficient cell lines were established from such
      foci, and lines with similar ras mRNA levels selected for further analysis. Ras
      transformed cell lines from both wildtype and OPN-deficient mice could form
      colonies in soft agar indicating that this process can occur in the absence of
      OPN. However, the ability of the OPN-deficient cell lines to form colonies was
      reduced as compared to wildtype cell lines. Tumorigenesis in syngeneic and nude
      mice was assessed for a subset of cell lines that formed colonies efficiently in
      soft agar. Cell lines unable to make OPN formed tumors in these mice much more
      slowly than wildtype cells, despite similar growth of the cells on plastic and in
      soft agar. Taken together, these results indicate that maximal transformation by
      ras requires OPN expression, and implicate increased OPN expression as an
      important effector of the transforming activity of the ras oncogene.

PMID- 10901365
TI  - Tissue factor expression in breast cancer tissues: its correlation with prognosis
      and plasma concentration.
AB  - Tissue factor (TF), an initiator of the extrinsic coagulation cascade, is
      expressed in a wide range of cancer cells and plays important roles in cancer
      progression and metastasis. Recently, the intracellular function of TF has been
      revealed to be involved in cancer invasion, independent of the blood coagulation
      pathway. To evaluate the clinical significance of TF expression, we performed an
      enzyme-linked immunosorbent assay (ELISA) in the plasma of 67 breast cancer
      patients and immunohistochemistry in 213 breast cancer tissues. In the ELISA
      study, we showed an up-regulation of plasma TF concentration in breast cancer
      patients compared with normal controls. Immunohistochemistry demonstrated that TF
      was expressed in tumour cells and stromal cells and tumour TF expression closely
      correlated with stromal TF expression (P = 0.0005). The concentration of plasma
      TF was associated with tissue TF expression in both tumour and stroma. The
      multivariate analysis demonstrated that tumour TF expression was an independent
      prognostic indicator for overall survival (P = 0.0452). Our data show that plasma
      TF concentration reflects tissue TF expression and tumour TF expression can
      provide some predictive value for prognosis and distant metastasis, which
      indicates the importance of TF function in tumour progression.

PMID- 10901366
TI  - Limited neuropeptide Y precursor processing in unfavourable metastatic
      neuroblastoma tumours.
AB  - Neuropeptide Y (NPY) is found at high concentrations in neural crest-derived
      tumours and has been implicated as a regulatory peptide in tumour growth and
      differentiation. Neuroblastomas, ganglioneuromas and phaeochromocytomas with
      significant concentrations of NPY-like immunoreactivity were investigated for
      different molecular forms of NPY and for significance of proNPY processing. Gel
      permeation chromatography identified intact NPY (1-36) in all tumours, whereas
      proNPY (69 amino acids) was detected only in control adrenal tissue and malignant
      neuroblastomas. Purification of NPY-like immunoreactivity in tumour extracts and
      structural characterization revealed that both NPY (1-36) and the truncated form
      NPY (3-36) was present. The degree of processing of proNPY to NPY in tumour
      tissue was lower in advanced neuroblastomas with regional or metastatic spread
      (stage 3 and 4) (n = 6), (41%, 12-100%, median, range), compared to the less
      aggressive stage 1, 2 and 4S tumours (n = 12), (93%; 69-100%), (P= 0.012). ProNPY
      processing of less than 50% was correlated with poor clinical outcome (P =
      0.004). MYCN oncogene amplification was also correlated to a low degree of proNPY
      processing (P = 0.025). In summary, a low degree of proNPY processing was
      correlated to clinical advanced stage and poor outcome in neuroblastomas.
      ProNPY/NPY processing generated molecular forms of NPY with known differences in
      NPY-receptor selectivity, implicating a potential for in vivo modulation of NPY
      like effects in tumour tissue.

PMID- 10901367
TI  - Evidence for susceptibility genes to familial Wilms tumour in addition to WT1,
      FWT1 and FWT2.
AB  - Three loci have been implicated in familial Wilms tumour: WT1 located on
      chromosome 11p13, FWT1 on 17q12-q21, and FWT2 on 19q13. Two out of 19 Wilms
      tumour families evaluated showed strong evidence against linkage at all three
      loci. Both of these families contained at least three cases of Wilms tumour
      indicating that they were highly likely to be due to genetic susceptibility and
      therefore that one or more additional familial Wilms tumour susceptibility genes
      remain to be found.

PMID- 10901368
TI  - Limitations of the nested reverse transcriptase polymerase chain reaction on
      tyrosinase for the detection of malignant melanoma micrometastases in lymph
      nodes.
AB  - The specificity and sensitivity of the nested reverse transcriptase polymerase
      chain reaction (RT-PCR) on tyrosinase was studied, for the detection of
      micrometastases of malignant melanoma. The specificity was assessed in the blood
      of six healthy donors, four patients with non-melanoma cancers of which one
      patient was treated with granulocyte-colony stimulating factor. Lymph nodes of
      nine patients without malignant melanoma were tested and four cell lines of
      various other tumours. Six of the nine non-melanoma lymph nodes were positive in
      this assay. The sensitivity was tested in a spike experiment in vitro, using a
      melanoma cell line. The detection limit was ten melanoma cells per 10(7)
      peripheral blood lymphocytes.

PMID- 10901369
TI  - Death from early colorectal cancer is predicted by the presence of transcripts of
      the REG gene family.
AB  - An intrinsic component of colorectal carcinogenesis may be the capacity to
      activate regenerative responses simultaneously with inhibition of apoptosis.
      Since apoptosis is known to be inhibited in colorectal cancer, this study sought
      evidence for the activation of the REG family of genes which are considered to be
      activated during regeneration of intestinal mucosa. Transcripts for the REG gene
      were found in 53% of colorectal cancers and for the PAP gene in 60% of colorectal
      cancers, by RT-PCR. Using in situ hybridization, the REG transcripts were found
      to be present in the tumour cells themselves rather than inflammatory or stromal
      cells. There were no significant correlations between the expression of these two
      genes and tumour stage, age or sex of the patient population or tumour site.
      However, in patients with non-metastatic disease who underwent ostensibly
      curative surgery, the expression of REG alone and co-expression of REG with PAP
      had a highly significantly adverse effect on survival. These data provide support
      for the concept that, in some tumours, carcinogenesis involves a regenerative
      process which co-exists with apoptotic inhibition and may provide a valuable
      selective indicator of the need for adjuvant therapy in those patients with early
      stage colorectal cancer whose disease is destined to recur after curative
      surgery.

PMID- 10901370
TI  - Prognostic significance of vascular endothelial growth factor expression in human
      ovarian carcinoma.
AB  - The influence of vascular endothelial growth factor (VEGF) expression and
      microvessel density (MVD) on prognosis and the relationship between VEGF
      expression and MVD in ovarian carcinoma are not well defined. We studied VEGF
      expression in parallel with MVD by immunohistochemistry in 94 ovarian tumours (64
      malignant, 13 borderline, and 17 benign) and correlated the results with the
      clinicopathologic prognostic factors of the disease to clarify their significance
      in this disease. Assessment of VEGF mRNA isoforms by RT-PCR was also performed.
      Of the malignant, borderline, and benign ovarian tumours respectively, two (3%),
      four (31%) and 16 (94%) were negative, 31 (48%), seven (54%) and one (6%) had low
      expressions, and 31 (48%), two (15%) and none (0%) had high expressions of VEGF.
      There were significant associations between the VEGF expression and disease stage
      (P= 0.002), histologic grade (P= 0.0004), and patient outcome (P= 0.0002). MVD
      did not correlate significantly with the clinicopathologic parameters. Likewise,
      no correlation was found between MVD and VEGF expression. The survival of
      patients with high VEGF expression was significantly worse than that of patients
      with low and negative VEGF expression (P = 0.0004). Multivariate analysis
      revealed that disease stage and VEGF expression were significant and independent
      prognostic indicators of overall survival time (P = 0.008 and P = 0.006
      respectively). These findings suggest that in conjunction with the established
      clinicopathologic prognostic parameters of ovarian carcinoma, VEGF expression may
      enhance the predictability of patients at high risk for tumour progression who
      are potential candidates for further aggressive therapy.

PMID- 10901371
TI  - NY-ESO-1 tumour associated antigen is a cytoplasmic protein detectable by
      specific monoclonal antibodies in cell lines and clinical specimens.
AB  - NY-ESO-1 gene encodes a novel member of the cancer/testis (CT) family of human
      tumour-associated antigens (TAA). Specific monoclonal antibodies (mAb) have
      identified the corresponding gene product in lysates of tumour cell lines as a 22
      kDa protein but no data are available concerning its intracellular location or
      distribution within neoplastic tissues. We have generated NY-ESO-1 specific mAbs
      recognizing the target molecule in cytospin preparations and in sections from
      clinical tumour specimens. These reagents identify NY-ESO-1 TAA in melanoma cell
      lines expressing the specific gene as a cytoplasmic protein, sharing the
      intracellular location of most MAGE TAA. In a series of 12 melanoma specimens,
      specific staining, limited to neoplastic cells, was detectable in the five cases
      where NY-ESO-1 gene expression was observed. In two of them over 90% of tumour
      cells showed evidence of positive staining. Lower percentages of positive
      neoplastic cells ranging between single cells and 50% were observed in the
      remaining tumours. These data suggest that active specific immunotherapies
      targeting NY-ESO-1, alone or in combination with other TAA could be of high
      clinical relevance in sizeable subgroups of melanoma patients.

PMID- 10901372
TI  - Low E-cadherin expression in bladder cancer at the transcriptional and protein
      level provides prognostic information.
AB  - We studied E-cadherin down-regulation at the protein level in frozen sections of
      111 bladder tumours and 13 normal bladder specimens by means of
      immunohistochemistry, and at the mRNA level by semi-quantitative RT-PCR in 40 of
      the same tumours. Results indicate that E-cadherin expression detected by
      immunohistochemistry correlated with both stage and grade (P < 0.0001 and P <
      0.001, respectively). Analysis of recurrence, progression and survival over a
      mean period of 36 months after surgery in the entire cohort showed that abnormal
      E-cadherin immunoreactivity correlated strongly with poor outcome (log-rank test:
      P = 0.001, P = 0.0001 and P = 0.0003, respectively). In multistep logistic
      regression analysis, only E-cadherin status and stage had significant additional
      prognostic value (P= 0.008 and OR = 0.2; P= 0.03 and OR = 3.6, respectively).
      Survival estimates derived from RT-PCR transcript quantification differed
      significantly for low and high expression (log-rank test: P = 0.0006). These
      results suggest that the alteration occurs at the transcriptional level and
      support the clinical and biological relevance of cell adhesion molecules in
      bladder cancer.

PMID- 10901373
TI  - Immunohistochemical detection of membrane-type-1-matrix metalloproteinase in
      colorectal carcinoma.
AB  - We investigated whether the expression of membrane-type-1 matrix
      metalloproteinase (MT1-MMP), matrix metalloproteinase-2 (MMP-2) and tissue
      inhibitor of metalloproteinase-2 (TIMP-2) was consistent with the proposed roles
      of these proteins in promoting metastasis in colorectal cancer. The expression of
      MT1-MMP was significantly more frequent in deeply invasive carcinomas (P = 0.007)
      and in cases of vascular invasion (P = 0.02). The frequency of detection of MMP-2
      in the stroma was much greater in vascular invasion-positive cases (42%) than in
      negative cases (20%; P = 0.02). The rate of detection of TIMP-2 in tumour cell
      cytoplasm increased with the depth of invasion (P = 0.03). TIMP-2 in the stroma
      was found more frequently in tumours with lymphatic invasion and lymph node
      metastasis (P < 0.05). Significant correlations were found between detection of
      MT1-MMP and MMP-2 in tumour cell cytoplasm (P < 0.05), of MT1-MMP and TIMP-2 in
      tumour cell cytoplasm (P < 0.01), and of MMP-2 and TIMP-2 in tumour cell
      cytoplasm (P < 0.01). Immunohistochemical detection of MT1-MMP and TIMP-2 might
      be useful for monitoring infiltration in colorectal carcinoma but is not
      correlated with distant metastases.

PMID- 10901374
TI  - Induction of thymidine phosphorylase as a pharmacodynamic end-point in patients
      with advanced carcinoma treated with 5-fluorouracil, folinic acid and interferon
      alpha.
AB  - Thymidine phosphorylase (TP) is an essential enzyme for the biochemical
      activation of 5-fluorouracil (5-FU). Interferon upregulates TP in vivo, although
      the dose and schedule of interferon for optimal biomodulation of 5-FU is not
      known. In this study, TP activity was measured in peripheral blood lymphocytes
      (PBLs) from patients with advanced carcinoma receiving treatment with 5-FU and
      folinic acid. Cohorts of patients were treated with interferon alpha (IFNalpha),
      immediately prior to 5-FU/folinic acid, at doses of 3 MIU m(-2), 9 MIU m(-2) and
      18 MIUm(-2). IFNalpha was administered on day 0 cycle two, day-1 and day 0 cycle
      three and day-2, day-1 and day 0 cycle four. A fourth cohort was treated with
      IFNalpha 9 MIU m(-2) three times per week from cycle 2 onwards. Twenty-one
      patients were entered into the study with 19 evaluable for response. Six patients
      (32%) had stable disease and 13 (68%) progressive disease. There were no grade-IV
      toxicities. TP activity was detected in PBLs from all patients with wide
      interpatient variability in constitutive TP activity prior to chemotherapy, and
      in response to IFNalpha. 5-FU/folinic acid alone did not induce TP activity but a
      single dose of IFNalpha led to upregulation of TP within 2 h of administration
      with a further increase by 24 h (signed rank test, P = 0.006). TP activity
      remained elevated for at least 13 days (signed rank test, P= 0.02). There were no
      significant differences in TP activity between schedules or with additional doses
      of IFNalpha. A single dose of IFNalpha as low as 3 MIU m(-2) can cause sustained
      elevation of PBL TP activity in vivo indicating that biochemical markers are
      important pharmacodynamic endpoints for developing optimal schedules of IFNalpha
      for biomodulation of 5-FU.

PMID- 10901375
TI  - Disparate responses of tumour vessels to angiotensin II: tumour volume-dependent
      effects on perfusion and oxygenation.
AB  - Perfusion and oxygenation of experimental tumours were studied during angiotensin
      II (AT II) administration whereby the rate of the continuous AT II infusion was
      chosen to increase the mean arterial blood pressure (MABP) by 50-70 mmHg. In
      subcutaneous DS-sarcomas the red blood cell (RBC) flux was assessed using the
      laser Doppler technique and the mean tumour oxygen partial pressure (pO2) was
      measured polarographically using O2-sensitive catheter and needle electrodes.
      Changes in RBC flux with increasing MABP depended mainly on tumour size. In small
      tumours, RBC flux decreased with rising MABP whereas in larger tumours RBC flux
      increased parallel to the MABP. As a result of these volume-dependent effects on
      tumour blood flow, the impact of AT II on tumour pO2 was also mainly tumour
      volume-related. In small tumours oxygenation decreased with increasing MABP
      during AT II infusion, whereas in large tumours a positive relationship between
      blood pressure and O2 status was found. This disparate behaviour might be the
      result of the co-existence of two functionally distinct populations of tumour
      vessels. In small tumours, perfusion decreases presumably due to vasoconstriction
      of pre-existing host vessels feeding the tumour. In larger malignancies, newly
      formed tumour vessels predominate and seem not to have this vasoresponsive
      capability (lack of smooth muscle cells and/or AT receptors), resulting in an
      improvement of perfusion which is not tumour-related per se, but is due to the
      increased perfusion pressure.

PMID- 10901376
TI  - Biodistribution and pharmacokinetics of 111In-DTPA-labelled pegylated liposomes
      in a human tumour xenograft model: implications for novel targeting strategies.
AB  - The biodistribution and pharmacokinetics of 111In-DTPA-labelled pegylated
      liposomes in tumour-bearing nude mice was studied to examine possible
      applications of pegylated liposome-targeted anti-cancer therapies. Nude mice
      received an intravenous injection of 100 microl of 111In-DTPA-labelled pegylated
      liposomes, containing 0.37-0.74 MBq of activity. The t1/2alpha and t1/2beta of
      111In-DTPA-labelled pegylated liposomes were 1.1 and 10.3 h, respectively. Tumour
      uptake was maximal at 24 h at 5.5 +/- 3.0% ID g(-1). Significant
      reticuloendothelial system uptake was demonstrated with 19.3 +/- 2.8 and 18.8 +/-
      4.2% ID g(-1) at 24 h in the liver and spleen, respectively. Other sites of
      appreciable deposition were the kidney, skin, female reproductive tract and to a
      lesser extent the gastrointestinal tract. There was no indication of cumulative
      deposition of pegylated liposomes in the lung, central nervous system,
      musculoskeletal system, heart or adrenal glands. In contrast, the t1/2alpha and
      t1/2beta of unencapsulated 111In-DTPA were 5 min and 1.1 h, respectively, with no
      evidence of accumulation in tumour or normal tissues. Incubation of 111In-DTPA
      labelled pegylated liposomes in human serum for up to 10 days confirmed that they
      are very stable, with only minor leakage of their contents. The potential
      applications of pegylated liposomes in the arena of targeted therapy of solid
      cancers are discussed.

PMID- 10901377
TI  - Differential and antagonistic effects of 9-cis-retinoic acid and vitamin D
      analogues on pancreatic cancer cells in vitro.
AB  - Retinoids and vitamin D are known to exert important anti-tumour effects in a
      variety of cell types. In this study the effects of 9-cis-retinoic acid (9cRA)
      the vitamin D analogues EB1089 and CB1093 on three pancreatic adenocarcinoma cell
      lines were investigated. All compounds caused inhibition of in vitro growth but
      the vitamin D analogues were generally the more potent growth inhibitors. They
      were also more effective on their own than in combination with 9cRA. Growth
      arrest correlated with an increased proportion of cells in the G0/G1 phase.
      Apoptosis was induced in the three cell lines by 9cRA, whereas neither EB1089 nor
      CB1093 had this effect. Furthermore, addition of EB1089 or CB1093 together with
      9cRA resulted in significantly reduced apoptosis. Our results show that retinoic
      acids as well as vitamin D analogues have inhibitory effects on pancreatic tumour
      cells but different and antagonistic mechanisms seem to be employed.

PMID- 10901378
TI  - Gene expression profiles of human endometrial cancer samples using a cDNA
      expression array technique: assessment of an analysis method.
AB  - The recently developed cDNA expression array technique can be used to generate
      gene-expression fingerprints of tumour specimens. To gain insight into molecular
      mechanisms involved in the development and progression of cancer, this cDNA
      expression array technique could be a useful tool, however, no established
      methods for interpreting the results are yet available. We used the Atlas cancer
      cDNA expression array (Clontech, USA) for analysing total RNA isolated from four
      human endometrial carcinoma samples (two cell-lines and two tissue samples), one
      benign endometrial tissue sample and a human breast cancer cell-line, in order to
      develop a method for analysing the array data. The obtained gene-expression
      profiles were highly reproducible. XY-scatterplots and regression analysis of the
      logarithmic transformed data provided a practical method to analyse the data
      without the need of preceding normalization. Three genes (Decorin, TIMP3 and
      Cyclin D1) were identified to be differentially expressed between the benign
      endometrial tissue sample and the endometrial carcinoma samples (tissue and cell
      lines). These three genes may potentially be involved in cancer progression. A
      higher degree of similarity in gene-expression profile was found between the
      endometrial samples (tissue and cell-lines) than between the endometrial samples
      and the breast cancer cell-line, which is indicative for an endometrial tissue
      specific gene-expression profile.

PMID- 10901379
TI  - Human anti-CD30 recombinant antibodies by guided phage antibody selection using
      cell panning.
AB  - In various clinical studies, Hodgkin's patients have been treated with anti-CD30
      immunotherapeutic agents and have shown promising responses. One of the problems
      that appeared from these studies is the development of an immune response against
      the nonhuman therapeutics, which limits repeated administration and reduces
      efficacy. We have set out to make a recombinant, human anti-CD30 single-chain
      variable fragment (scFv) antibody, which may serve as a targeting moiety with
      reduced immunogenicity and more rapid tumour penetration in similar clinical
      applications. Rather than selecting a naive phage antibody library on recombinant
      CD30 antigen, we used guided selection of a murine antibody in combination with
      panning on the CD30-positive cell line L540. The murine monoclonal antibody Ki-4
      was chosen as starting antibody, because it inhibits the shedding of the
      extracellular part of the CD30 antigen. This makes the antibody better suited for
      CD30-targeting than most other anti-CD30 antibodies. We have previously isolated
      the murine Ki-4 scFv by selecting a mini-library of hybridoma-derived phage scFv
      antibodies via panning on L540 cells. Here, we report that phage display
      technology was successfully used to obtain a human Ki-4 scFv version by guided
      selection. The murine variable heavy (VH) and light (VL) chain genes of the Ki-4
      scFv were sequentially replaced by human V gene repertoires, while retaining only
      the major determinant for epitope-specificity: the heavy-chain complementarity
      determining region 3 (CDR3) of murine Ki-4. After two rounds of chain shuffling
      and selection by panning on L540 cells, a fully human anti-CD30 scFv was
      selected. It competes with the parental monoclonal antibody Ki-4 for binding to
      CD30, inhibits the shedding of the extracellular part of the CD30 receptor from
      L540 cells and is thus a promising candidate for the generation of anti-CD30
      immunotherapeutics.

PMID- 10901381
TI  - Cellular glutathione as a determinant of the sensitivity of colorectal tumour
      cell-lines to ZD2767 antibody-directed enzyme prodrug therapy (ADEPT).
AB  - ZD2767P, a nitrogen mustard glutamate prodrug, is currently being evaluated in
      Phase 1 clinical trials of antibody directed enzyme prodrug therapy (ADEPT).
      There was no significant relationship between basal glutathione (GSH)
      concentration and sensitivity to ZD2767P + carboxpeptidase G2 (CPG2) in
      colorectal tumour cell-lines. Depletion of intracellular GSH using buthionine
      sulfoximine (BSO) resulted in only a modest potentiation of ZD2767P + CPG2
      activity and hence BSO is unlikely to markedly enhance the activity of this ADEPT
      treatment.

PMID- 10901380
TI  - The Fc-region of a new class of intact bispecific antibody mediates activation of
      accessory cells and NK cells and induces direct phagocytosis of tumour cells.
AB  - Bispecific antibodies (bsAb) are considered as promising tools for the
      elimination of disseminated tumour cells in a minimal residual disease situation.
      The bsAb-mediated recruitment of an immune effector cell in close vicinity of a
      tumour cell is thought to induce an antitumoural immune response. However,
      classical bispecific molecules activate only a single class of immune effector
      cell that may not yield optimal immune responses. We therefore constructed an
      intact bispecific antibody, BiUII (anti-CD3 x anti-EpCAM), that not only
      recognizes tumour cells and T lymphocytes with its two binding arms, but also
      binds and activates Fcgamma-receptor positive accessory cells through its Fc
      region. We have demonstrated recently that activated accessory cells contribute
      to the bsAb-induced antitumoural activity. We now analyse this stimulation in
      more detail and demonstrate here the BiUII-induced upregulation of activation
      markers like CD83 and CD95 on accessory cells and the induction of neopterin and
      biopterin synthesis. Experiments with pure cell subpopulations revealed binding
      of BiUII to CD64+ accessory cells and CD16+ NK cells, but not to CD32+ B
      lymphocytes. We provide further evidence for the importance of the Fc-region in
      that this bispecific molecule stimulates Fcgamma-R-positive accessory cells to
      eliminate tumour cells in vitro by direct phagocytosis.

PMID- 10901383
TI  - Registration of ovarian cancer in England and Wales.

PMID- 10901382
TI  - Mechanisms of acquired resistance to 2-(4-aminophenyl)benzothiazole (CJM 126, NSC
      34445).
AB  - 2-(4-aminophenyl)benzothiazole (CJM 126) elicits potent growth inhibition in
      human-derived breast carcinoma cell lines, including oestrogen receptor-positive
      (ER+) MCF-7wt cells. Analogues substituted in the 3' position with I (DF 129),
      CH3 (DF 203), or Cl (DF 229) possess an extended profile of antitumour activity
      with remarkable selective activity in cell lines derived from solid tumours
      associated with poor prognosis, e.g. breast, ovarian, renal and colon. Growth
      inhibition occurs via unknown, possibly novel mechanism(s) of action. Two cell
      lines have been derived from sensitive MCF-7wt breast cancer cells (IC50 value <
      0.001 microM) following long-term exposure to 10 nM or 10 microM CJM 126, MCF
      7(10 nM 126) and MCF-7(10 microM 126) respectively, which demonstrate acquired
      resistance to this agent (IC50 > 30 microM) and cross-resistance to DF 129, DF
      203 and DF 229. Sensitivity to tamoxifen, benzo[a]pyrene (BP), mitomyin C,
      doxorubicin and actinomycin D is retained. Resistance may, in part, be conferred
      by the constitutively increased expression of bcl-2 and p53 proteins detected in
      MCF-7(10 nM 126) and MCF-7(10 microM 126 lysates. Significantly decreased
      depletion of CJM 126 (30 microM) from nutrient medium of MCF-7(10 microM 126)
      cells was observed with predominantly cytoplasmic drug localization and
      negligible DNA strand breaks. N-acetyl transferase (NAT)1 and NAT2 proteins were
      expressed by all three MCF-7 sub-lines, but significantly higher expression of
      NAT2 was accompanied by enhanced acetylation efficacy in MCF-7(10 nM 126) cells.
      In contrast, CJM 126 (30 microM) was rapidly depleted from nutrient medium of MCF
      7(10 microM 126) culture and accessed nuclei of these cells exerting damage to
      DNA. The major biotransformation product of CJM 126 in MCF-7(10 microM 126) cells
      was 2-(4-aminophenyl)-6-hydroxybenzothiazole (6-OH 126). This metabolite
      possessed no antitumour activity. Accordingly, in this sub-line, low constitutive
      expression and activity of cytochrome P450 (CYP) 1A1 was detected.

PMID- 10901384
TI  - Role of voltage-gated Na+ channels in hypoxia-induced neuronal injuries.
AB  - 1. Mammalian neurons in the central nervous system are vulnerable to oxygen
      deprivation. In clinical conditions, such as stroke or apnoea, permanent loss of
      neuronal functions can occur within minutes of severe hypoxia. 2. Recent studies
      have focused on the role of Na+ in acute neuronal responses to hypoxia. These
      studies have shown that the influx of extracellular Na+ is an important factor in
      hypoxia-induced injury and that blockade of voltage-gated Na+ channels reduces
      hypoxic responses and injury of neurons. Yet, the mechanism underlying the effect
      of blockade of Na+ channels on hypoxic injury is unclear. 3. The aim of the
      present review is to discuss the above topics given the current understanding of
      the role of Na+ channels in hypoxia and its implications on therapeutic strategy
      for preventing hypoxia-induced neurological damage. 4. It has been known that the
      maintenance of ionic homeostasis and membrane properties in neurons are improved
      by reducing the activity of voltaged-gated Na+ channels during acute hypoxia. 5.
      Recent studies suggest that persistent Na+ current and Na+-dependent exchangers
      may play a role in Na+ influx and neuronal injury during hypoxia. 6. The
      neuroprotective action of blockers of the Na+ channel may also be via the
      improved maintainance of intracellular energy levels because the action is
      dependent on cellular energy levels and extracellular glucose during hypoxia. 7.
      Hence, the blockade of voltage-gated Na+ channels reduces the excitability of
      neurons, Na+ influx and the accumulation of intracellular Na+. These improve the
      ionic homeostasis and cellular energy levels and, thus, prevent hypoxia-induced
      neuronal injury and neuronal damage mediated by Ca2+ overload.

PMID- 10901385
TI  - Physiological effects of extracellular nucleotides in the inner ear.
AB  - 1. Electrochemical homeostasis, sound transduction and auditory neurotransmission
      in the cochlea are influenced by extracellular purines and pyrimidines. 2.
      Evidence that ATP and related nucleotides influence inner ear function arises
      from a considerable number of cellular, molecular and physiological studies in
      vitro and in vivo. 3. With a full understanding of these processes, which include
      ionotropic (P2X receptor) and metabotropic (P2Y receptor) signal transduction
      pathways, signal termination involving ecto-nucleotidases and recycling via
      nucleoside transporters, exciting possibilities emerge for treating hearing
      disorders, such as Meniere's disease, tinnitus and sensorineural deafness.

PMID- 10901387
TI  - Reversal of anticancer drug resistance by macrolide antibiotics in vitro and in
      vivo.
AB  - 1. The combined effects of the macrolide antibiotics erythromycin, josamycin,
      clarithromycin and YM17K (3,4'-dideoxy mycaminosyl tylonolide hydrochloride) on
      in vitro intracellular accumulation of vinblastine or cyclosporine (Cs)A and on
      the in vivo antitumour activity of vinblastine were investigated using mouse
      leukaemia P388 cells (P388/S) and anticancer drug-resistant (P388/ADR) cells.
      These effects were compared with those of a calcium antagonist (verapamil) or
      immunosuppressants (FK506 and CsA). 2. All tested macrolide antibiotics increased
      the accumulation of both vinblastine and CsA in P388/ADR cells in a dose
      dependent manner, but their potency was lower than that of verapamil, CsA or
      FK506. 3. When vinblastine (200 microg/kg) was administered intraperitoneally
      with each of the macrolide antibiotics (10 or 100 mg/kg) or with verapamil (25
      mg/kg) once a day for 10 days in P388/ADR-bearing mice, combined effects of
      vinblastine with the macrolide antibiotics (erythromycin, clarithromycin and
      YM17K) or verapamil were observed. 4. The present study suggests that macrolide
      antibiotics may overcome anticancer drug resistance by inhibiting the binding of
      vinblastine or CsA to P-glycoprotein in P388/ADR cells. 5. We believe that these
      results are encouraging for combination chemotherapy to overcome P-glycoprotein
      dependent anticancer drug-resistant tumours in clinical practice.

PMID- 10901386
TI  - Cytochrome p450-dependent metabolites of arachidonic acid and renal function in
      the rat.
AB  - 1. The present study examined whether renal cytochrome P450 (CYP450)-derived
      eicosanoids influence the pressure-natriuretic and haemodynamic responses to
      elevated renal perfusion pressure (RPP) in the rat. 2. Natriuresis and diuresis,
      as well as changes in renal blood flow (RBF) and glomerular filtration rate (GFR)
      following step-wise elevations in RPP from 75 to 125 mmHg were compared in
      control rats and in rats treated with 12,12-dibromodecenoic acid (DBDD; 2.5 mg/kg
      per h; n = 5), an inhibitor of omega/omega-1 hydroxylase, or miconazole (1.3
      mg/kg per h; n = 7), an inhibitor of epoxygenase. 3. In control rats, sodium
      excretion (U(Na)V) and urine volume (UV) increased five-fold when RPP was
      increased from 75 to 125 mmHg, while RBF and GFR increased two-fold when RPP
      increased from 75 to 100 mmHg, with no further increase between 100 and 125 mmHg,
      the autoregulatory range. 4. Miconazole, but not DBDD, altered the pressure
      natriuresis relationship, exaggerating the increases in U(Na)V and UV three- to
      four-fold when RPP was increased from 100 to 125 mmHg. 5. In contrast, DBDD
      eliminated the autoregulatory response because it abolished the plateau in RBF
      and GFR when RPP was increased from 100 to 125 mmHg, whereas miconazole was
      without effect. 6. These results suggest that CYP450-dependent omega/omega-1
      hydroxylase metabolites of arachidonic acid contribute to vascular responses,
      while epoxygenase metabolites contribute to renal tubular responses to
      alterations in RPP in the rat.

PMID- 10901388
TI  - Delayed hypotensive effect of the thromboxane A2/prostaglandin H2 receptor
      antagonist S-1452 in spontaneously hypertensive rats.
AB  - 1. Several lines of evidence indicate that thromboxane (Tx) A2 may contribute to
      the development and maintenance of hypertension. The present study was undertaken
      to evaluate the role of TxA2 in the development of hypertension in spontaneously
      hypertensive rats (SHR) by using an orally active, highly specific
      TxA2/prostaglandin H2 receptor antagonist S-1452. 2. Vehicle (1% arabic gum
      solution) alone was given orally to Wistar-Kyoto (WKY) rats (n = 15) and SHR (n =
      14), while S-1452 (10 mg/kg per day, twice daily) was administered orally to SHR
      (n = 16) for 18 weeks (from 5 to 23 weeks of age). 3. No significant difference
      was observed in tail-cuff blood pressure (BP) between vehicle- and S-1452-treated
      SHR before and at 5 and 11 weeks after treatment. Thereafter, BP was further
      elevated in vehicle-treated SHR, but was significantly blunted in SHR treated
      with S-1452 at 15 (224+/-8 vs 211+/-13 mmHg; P < 0.01) and 18 weeks (227+/-9 vs
      206+/-10 mmHg; P < 0.001); this was associated with reduced proteinuria. 4.
      Urinary TxB2 in vehicle-treated SHR, especially during the early period, was
      significantly greater than that in WKY rats, while no significant difference was
      observed in urinary 6-ketoprostaglandin F1alpha (6-keto-PGF1alpha) between the
      two groups. Treatment with S-1452 reduced urinary excretion of TxB2 at 18 weeks.
      5. The present study shows that S-1452, at the dose used, does not reduce BP
      during the early period of the development of hypertension. These results suggest
      that the role of enhanced TxA2 production in the development of hypertension is
      small, if any, in SHR. Delayed response of BP may be independent of the direct
      pharmacological effects of S-1452.

PMID- 10901389
TI  - Relative timing of inspiration and expiration affects respiratory sinus
      arrhythmia.
AB  - 1. The effect of a variation in inspiration and expiration times on heart rate
      variability was studied in 12 healthy subjects (mean age 30+/-6 years; five
      females). 2. Two 2 min trials of controlled breathing, with either short
      inspiration followed by long expiration or long inspiration followed by short
      expiration, were compared. Average expiration/inspiration time ratios were 1.0
      and 3.4, respectively. The respiration rate in both trials was approximately 10
      cycles/min. 3. In trials with short inspiration followed by long expiration,
      respiratory sinus arrhythmia (RSA; as measured by mean absolute differences and
      by the high frequency band) was significantly larger than in trials with long
      inspiration followed by short expiration. This effect could not be accounted for
      by differences in respiration rate or respiratory amplitude. The higher RSA
      during fast/slow respiration is primarily due to a more pronounced phasic heart
      rate increase during inspiration, indicating that inspiratory vagal blockade is
      sensitive to the steepness of inspiration. 4. Respiration rate and tidal volume
      are respiratory variables known to modulate RSA. The results of the present study
      indicate that RSA can also be modulated by a third respiratory variable, the
      expiratory/inspiratory time ratio.

PMID- 10901390
TI  - Effect of cold on fetal heart rate and its variability.
AB  - 1. The effects of cold saline (25 mL) injected over the fetal skin on fetal heart
      rate (HR) and HR variability (HRV), measured as the coefficient of variation (CV)
      in pulse interval (PI) and by power spectral analysis (PSA), were measured in 10
      chronically catheterized fetal sheep aged 140-144 days. To determine the extent
      to which effects on HR and HRV were mediated by the sympathoadrenal
      neuroendocrine axis and the cardiac vagus, experiments were performed before and
      after beta-adrenoreceptor blockade with propranolol (n = 12 fetuses) or before
      and after cardiac vagal blockade with atropine (n = 4 fetuses). 2. Injection of
      ice-cold saline over the skin caused an immediate rise in mean arterial pressure
      (MAP) from 46+/-1 to 55+/-1 mmHg (P < 0.001) and HR from 156+/-2 to 182+/-2
      b.p.m. (P < 0.001). Heart rate variability, measured as CV of PI, rose from 3.5+/
      0.2 to 8.0+/-0.2% (P < 0.001) and total power spectral density (PSD) increased
      from 78+/-6 to 278+/-16 units (P < 0.001) as measured by PSA. Within 100s, MAP,
      HR and HRV had returned to baseline. 3. Beta-adrenoreceptor blockade abolished
      all these changes in HR, HRV and PSD, but had no effect on changes in MAP.
      Atropine had no demonstrable effect on the responses to cold. 4. Therefore, the
      increase in fetal MAP, HR and HRV that occurred with stimulation of peripheral
      thermoreceptors was the result of increased activity of the sympathetic nervous
      system. Alterations in efferent cardiac vagal tone were not involved in the
      cardiac response to cold.

PMID- 10901391
TI  - Ammonia response to constant exercise: differences to the lactate response.
AB  - 1. We evaluated the plasma ammonia response to constant exercise at different
      intensities. Ten healthy male volunteers were asked to perform constant exercise
      for 15 min at five different intensities: 80, 90, 100, 110 and 120% of their
      ventilatory threshold (VT). Blood concentrations of lactate, ammonia and
      hypoxanthine were measured during and after exercise. 2. The concentration of
      lactate increased continuously during exercise intensities equivalent to 100, 110
      and 120% VT. Plasma ammonia began to increase at 6 min exercise and continued
      increasing during exercise at all five exercise intensities. Plasma hypoxanthine
      levels also increased continuously during exercise at all exercise intensities;
      however, they peaked at 5-10 min after exercise. The response of plasma ammonia
      and hypoxanthine increased with increasing intensities of exercise. 3. While the
      extent of the increase in lactate levels during exercise at 100, 110 and 120% VT
      was significantly higher than that at 80% VT, only the increase in ammonia and
      hypoxanthine levels at 120% VT were significantly higher than those at 80% VT. 4.
      In conclusion, the plasma ammonia response to constant exercise differed to the
      lactate and ammonia responses to short-term exhaustive exercise.

PMID- 10901392
TI  - Eicosapentaenoic acid stimulates nitric oxide production and decreases cardiac
      noradrenaline in diabetic rats.
AB  - 1. The aim of the present study was to investigate whether long-term oral
      administration of eicosapentaenoic acid increases nitric oxide (NO) production
      and affects cardiac sympathetic activity in rats with diabetes mellitus. 2. We
      measured changes in urinary excretion of NO3-, a stable NO metabolite, and
      cardiac noradrenaline (NA) concentrations in non-diabetic rats and streptozotocin
      induced diabetic rats treated with either ethyl icosapentate (EPA-E; 100 mg/kg
      per day; n = 10), a purified ethyl esterification product of eicosapentaenoic
      acid, or vehicle (distilled water; n = 10) for 6 weeks. The effects of N(G)-nitro
      L-arginine (L-NNA), a NO synthase inhibitor, on urinary NO3- excretion and
      cardiac NA concentrations were also investigated in diabetic rats treated with
      EPA-E. 3. Urinary NO3- excretion was higher at weeks 5 and 6 in diabetic rats
      treated with EPA-E than in diabetic rats treated with vehicle (week 5: 120+/-8 vs
      51+/-11 micromol/g per day, respectively (P<0.01); week 6: 279+/-83 vs 73+/-9
      micromol/g per day, respectively (P<0.01)). Cardiac NA concentrations were higher
      in diabetic rats than in non-diabetic rats and were decreased in the left atrium
      and both ventricles in diabetic rats treated with EPA-E compared with control.
      Systemic administration of L-NNA abolished the increase in urinary excretion of
      NO3- and the decrease in cardiac NA concentrations in diabetic rats treated with
      EPA-E. 4. Long-term oral administration of EPA-E may stimulate NO production and
      increased NO is likely to play a role in inhibiting enhanced cardiac sympathetic
      activity in diabetic rats.

PMID- 10901393
TI  - In vivo manipulation and continuous measurement of muscle blood flow with venous
      effluent sampling.
AB  - 1. An acute in vivo hindlimb skeletal muscle preparation was developed in
      anaesthetized sheep in order to facilitate studies of the effects of altered
      blood flow states on drug kinetics in skeletal muscle. 2. A continuous index of
      blood flow was recorded via ultrasonic Doppler probes on the femoral artery and
      vein. Skeletal muscle effluent blood was sampled via a catheter in the femoral
      vein proximal to the probe. Low- and high-blood flow states were achieved by
      direct femoral artery infusion of adrenaline (0.002-0.006 mg/min) or magnesium
      (0.4-1 mmol/min), which produced mean (+/-SD) stable flow states of 25+/-12 and
      185+/-56% (both n = 5) of baseline, respectively. The correlation coefficients
      between arterial and venous Doppler frequency shifts in five sheep during and
      after adrenaline infusion were 0.96 (indicating these vessels probably supplied
      and drained common tissue). 3. The venous Doppler frequency shifts were
      calibrated against timed collections of the femoral vein outflow to provide
      estimates of the low and normal blood flow states (mean flows of 2.8+/-1.7 and
      9.3+/-5.7mL/100 g per min; both n = 3) and against an indirect Kety-Schmidt
      method during low- and high-blood flow states (mean flows of 2.2+/-1.3 and 18.2+/
      7.0 mL/100 g per min; both n = 5). There was a generally good agreement between
      the two methods. 4. The tissue was neither hypoxic nor acidotic in the low- or
      high-flow states and altering the flow produced no change in muscle oxygen
      consumption, suggesting the flow changes were largely due to changes in
      resistance vessel tone. 5. Postmortem femoral artery dye injection and dissection
      of stained tissues showed the artery supplied 657+/-96 g (n = 5) of skeletal
      muscle and 42+/-20 g (n = 5) of other tissues. 6. It is concluded that the method
      is suitable for sampling predominantly muscle effluent blood at low- or high
      blood flow states according to experimental requirements.

PMID- 10901394
TI  - Endothelial cell responses to hypoxic stress.

PMID- 10901395
TI  - First report of active renin in rat amniotic fluid.
AB  - 1. Epidemiological studies indicate that a reduced birthweight increases the
      likelihood of human cardiovascular disease later in life. The role of hormonal
      factors in this finding is not known. Given that angiotensin II is believed to be
      a fetal regulator of growth, we have examined in the hypertensive Ren-2
      transgenic rat whether it has active renin in its amniotic fluid and whether this
      is associated with fetal underdevelopment. 2. We found that while the Sprague
      Dawley rat contained no active renin in its amniotic fluid near term (20 days),
      Ren-2 amniotic fluid contains high levels of active renin and is associated with
      a reduced fetal weight. 3. This is the first report of active renin in the rat
      and allows the possibility that renin overproduction plays a role in reduced
      fetal growth and the prenatal 'programming' of essential hypertension that has
      been proposed to occur in humans.

PMID- 10901396
TI  - Blockade of central angiotensin II does not affect the reduction in renal
      sympathetic nerve activity following a volume load in heart failure rabbits.
AB  - 1. We investigated the role in sympathetic nerve regulation of endogenous
      angiotensin (Ang)II in the brain in heart failure by examining the effect of
      losartan on the resting mean arterial blood pressure (MAP), heart rate (HR) and
      renal sympathetic nerve activity (RSNA) and the reflex reduction in RSNA elicited
      by acute volume expansion in conscious rabbits. 2. Heart failure was induced with
      doxorubicin (1 mg/kg, i.v., twice weekly for 6 weeks). On the experimental day,
      MAP, HR and RSNA were recorded in conscious rabbits before and after losartan (10
      microg; n = 6) or Ringer's (control; n = 5) injected in the fourth brain
      ventricle. Animals were then administered an acute volume load with the plasma
      expander Haemaccel (Hoechst Marion Roussel, Lane Cove, NSW, Australia; 2 mL/min,
      i.v., for 30 min). 3. Losartan did not significantly affect the resting basal
      levels of MAP, HR and RSNA. There was no significant difference between losartan-
      and Ringer's-treated animals. 4. Volume expansion in the control group elicited a
      significant reduction of 40% in RSNA. In the losartan-treated group, a similar
      reduction (42%) was observed. There was no significant difference between the
      treatments. The administration of losartan did not significantly affect MAP and
      HR during volume expansion compared with the control group. 5. We conclude that
      AngII in the brainstem does not play a major role in the maintenance of resting
      MAP, HR and RSNA or in the reflex reduction in RSNA elicited by volume expansion
      in the conscious rabbit with doxorubicin-induced heart failure.

PMID- 10901397
TI  - Carotid artery intima-medial thickness is increased in chronic renal failure.
AB  - 1. Chronic renal failure (CRF) is associated with rapidly progressive
      atherosclerotic vascular disease. In the present study, carotid arterial intima
      medial thickness (IMT) was assessed in a large cohort of patients with CRF and
      matched controls and related to risk factors. 2. A total of 159 subjects with CRF
      (serum creatinine > or =0.40 mmol/L) aged > 50 years (mean (+/-SD) 63.8+/-7.7
      years) and 159 healthy controls matched for age, sex and smoking status were
      studied. 3. The IMT was determined using B-mode ultrasound measurements of the
      far wall of both common carotid arteries and presented as the mean IMT. Fasting
      plasma homocysteine (tHcy) was measured in the CRF group. 4. Intima-medial
      thickness was significantly greater in CRF patients than controls (0.89+/-0.17 vs
      0.73+/-0.13 mm, respectively) after matching for age, sex and smoking status.
      Heart rate and pulse pressure were also significantly increased. The tHcy was
      increased two-fold in the CRF group (27.7+/-11.3 micromol/L; normal < 13.0
      micromol/L) and did not correlate with carotid IMT. 5. Compared with controls
      after adjusting for traditional risk factors, patients with CRF exhibit
      significantly increased IMT.

PMID- 10901400
TI  - Modelling the neural control of intrarenal blood flow.
AB  - 1. The aim of the present study was to produce a mathematical model that
      describes the way dynamic changes in renal sympathetic nerve activity affect
      renal, cortical and medullary blood flow. 2. Cortical blood flow (CBF) and
      medullary blood flow (MBF) were measured using laser-Doppler flowmetry and
      (total) renal blood flow (RBF) was measured by transit-time flowmetry in six
      pentobarbitone-anaesthetized rabbits. The renal nerves were stimulated with
      rectangular pulses of 2 msec width and constant voltage at frequencies of 0.5, 1,
      1.5, 2 and 3 Hz. 3. An exponential function with two parameters was applied;
      steady state gain and a dynamic constant for the blood flow reduction with
      stimulation. The steady state gain coefficients were similar for RBF and CBF, but
      significantly less for MBF. The time taken to reach minimum flow was less for MBF
      than for RBF and CBF. 4. The model parameters indicate that there is differential
      neural control of CBF and MBF.

PMID- 10901398
TI  - Basilar artery remodelling in the genetically hypertensive rat: effects of nitric
      oxide synthase inhibition and treatment with valsartan and enalapril.
AB  - 1. The structure of the basilar artery and the relationship of structure to blood
      pressure and ventricular hypertrophy was examined in genetically hypertensive
      (GH) rats, their control normotensive (N) Wistar strain, GH given the nitric
      oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) and
      GH given L-NAME and either valsartan or enalapril. 2. Systolic blood pressure
      (SBP; tail-cuff) was measured weekly from age 7-12 weeks. At the end of the
      experiment at 12 weeks, the basilar artery was fixed by perfusion and embedded in
      Technovit (Heraeus Kulzer GmbH, Werheim, Germany). Serial sections were cut and
      stained and stereological analysis applied to quantify the morphology of the
      vessels. Left ventricular (LV) mass was determined. 3. Both SBP and LV mass were
      significantly increased in GH compared with N (P < 0.001) and increased further
      in GH given L-NAME (P < 0.05). The GH L-NAME + valsartan and GH L-NAME +
      enalapril groups had significantly lower (P < 0.001) SBP and LV mass than the GH
      L-NAME group. 4. Basilar arteries in GH (which are frankly hypertensive, but have
      no apparent endothelial defect) showed hypotrophic inward remodelling compared
      with the N control group with no change in media to lumen ratio. 5. In the GH L
      NAME group, further inward remodelling occurred and the media to lumen ratio was
      increased compared with N (P < 0.01) and GH (P < 0.05). Valsartan treatment in GH
      L-NAME rats caused eutrophic outward remodelling. Enalapril caused hypertrophic
      outward remodelling, suggesting that the angiotensin II-stimulated growth was not
      entirely suppressed with an angiotensin-converting enzyme inhibitor or that there
      was a bradykinin effect with enalapril. 6. In GH with an endothelial defect
      induced by treatment with L-NAME, the further remodelling, together with an
      increased media to lumen ratio and the development of a stroke-like syndrome,
      indicates the NOS-inhibited GH rat may be a useful model for essential
      hypertension (where it is known that endothelial abnormalities exist) and where
      stroke can develop as a consequence of the hypertension.

PMID- 10901399
TI  - Effects of chronic inhibition of nitric oxide synthase in the genetically
      hypertensive rat.
AB  - 1. The effects of graded inhibition of nitric oxide synthase (NOS) on blood
      pressure in the genetically hypertensive (GH) rat strain and NOS activity in
      regions of the brain (cerebellum, striatum, hippocampus, frontal cortex and
      medulla oblongata) as a measure of body NOS inhibition were studied. 2. Male GH
      and normotensive (N) rats (n = 7-10 per group) were given N(G)-nitro-L-arginine
      methyl ester (L-NAME; 2, 5, 10 or 20 mg/kg per day in drinking water) from age 7
      weeks. Age- and weight-matched controls received water only. Systolic blood
      pressure (SBP) was measured weekly by the tail-cuff method from age 6 weeks. By
      age 10 weeks, rats were killed and NOS activity was measured. 3. Some GH rats
      that received over 5 mg/kg per day L-NAME developed stroke-like symptoms and were
      killed before the end of the treatment period. 4. No difference in NOS activity
      was found between untreated N and GH strains but, in those that received
      treatment, a graded inhibition was observed with increasing L-NAME dose levels.
      The frontal cortex in the GH strain given 20 mg/kg per day L-NAME had NOS
      inhibition of 90% where the N strain had 73% inhibition. Similar results were
      seen in the other areas of the brain. 5. Left ventricular mass, weight related,
      was significantly greater in the GH compared with N and was further elevated by
      treatment with L-NAME. 6. The SBP at 10 weeks was significantly elevated in GH
      rats by NOS inhibition with L-NAME in a dose-dependent manner; 25% for 2 mg/kg
      per day, 31% for 20 mg/kg per day (P < 0.001). There was a non-significant
      increase in BP in the N-treated groups (average change of 7.5%). 7. Nitric oxide
      synthase inhibition causing increased SBP in GH rats suggests an abnormality in
      the nitric oxide-L-arginine pathway in this strain.

PMID- 10901401
TI  - Type-C natriuretic peptide prevents development of experimental atherosclerosis
      in rabbits.
AB  - 1. We investigated the effect of local administration of type-C natriuretic
      peptide (CNP) on the endothelial dysfunction and development of an atheroma-like
      neointima induced by a peri-arterial collar in rabbits. 2. Peri-arterial collars
      were placed on both common carotid arteries allowing local treatment of the
      collared region with either CNP (10 micromol/L) or saline. After 7 days,
      uncollared (control) and collared sections were taken from both arteries for
      pharmacological and morphological analysis. 3. Application of the collar markedly
      attenuated (P < 0.05) endothelium-dependent vasorelaxation induced by
      acetylcholine (ACh); inhibition of 5-hydroxytryptamine contraction was 80+/-5% in
      control sections compared with 44+/-4% in collared sections from the same
      arteries. Local infusion of CNP (10 micromol/L) into the collar restored ACh
      induced vasorelaxation (74+/-3% from collared arteries + CNP vs 77+/-2% from
      control sections from the same arteries). 4. Type-C natriuretic peptide treatment
      also reduced (P < 0.05) intimal thickening compared with contralateral collared
      arteries (intima/media ratio 0.06+/-0.01 vs 0.16+/-0.01). 5. These results
      provide evidence that locally administered CNP is effective in preventing the
      endothelial dysfunction and development of a neointima in this model.

PMID- 10901402
TI  - Caries and its association with infant feeding and oral health-related behaviours
      in 3-4-year-old Brazilian children.
AB  - OBJECTIVES: To investigate the relationships between socio-demographic factors,
      infant feeding habits, oral hygiene and the prevalence and patterns of caries in
      Brazilian 3-4-year-olds. METHODS: Systematic random sampling was used to select
      children enrolled in municipal nurseries in Araraquara, Brazil, in 1998. Clinical
      examinations were carried out by one examiner using dmft and dmfs indices and WHO
      criteria. Questionnaires for information related to the socio-demographic
      background, oral hygiene and dietary history of the children were completed by
      their mothers. RESULTS: Caries was seen in 46% of the children; 17% of them had
      the more extensive pattern involving molars and incisors. Social class, mother's
      education, and age at which breast-feeding terminated showed statistically
      significant associations with caries. Feeding bottles with added sugars were
      still being given to 80% of the children. When the significant variables were
      taken into account only age at which breast-feeding terminated showed a
      significant relationship to the pattern of disease. Children who were never
      breast-fed or were breast-fed beyond the age of 24 months had a higher prevalence
      of the more extensive pattern of caries. CONCLUSIONS: The association between the
      length of time a mother breast-feeds and extensive caries should be a
      consideration in any local infant feeding policies or health promotion
      strategies. The duration for appropriate breast- or bottle-feeding should be
      emphasised.

PMID- 10901403
TI  - Trends in oral cancer rates in the United States, 1973-1996.
AB  - OBJECTIVES: To explore changes in demographic distribution, incidence and
      survival rates of oral cancer in the United States from 1973 through 1996.
      METHODS: From the Surveillance, Epidemiology, and End Results (SEER) data, we
      computed the proportion of oral cancer by demographic characteristics, site, and
      stage at diagnosis for 1973-84 and 1985-96. We estimated incidence and 5-year
      relative survival rates of oral cancer by age, gender, and race/ethnicity, and
      compared survival rates between the two periods. The estimated annual percent
      change (EAPC) was used to explore trends in incidence rate from 1973 through
      1996. RESULTS: Most of the tongue and floor of mouth cancers (>54%) reported
      during 1973-84 and 1985-96 had spread to a distant site at time of diagnosis. The
      age-adjusted annual incidence rates of oral cancer decreased among white men from
      1973 through 1996, but increased among black men aged 65-69 years, and among
      young white men (aged 30-34 years) and women (aged 25-29 years). These changes in
      trend were all statistically significant (testing EAPC=0 at the 0.05 level).
      Overall, there was no improvement in the 5-year relative survival rate of either
      whites or blacks with oral cancer. CONCLUSION: There was little change in early
      detection of oral cancer or in 5-year relative survival rates between 1973-84 and
      1985-96 in nine SEER regions. This suggests a deficiency in professional and
      public education regarding early diagnosis of oral cancer. Furthermore, the
      increasing trend of oral cancer among older black men and among younger whites
      merits further investigation.

PMID- 10901404
TI  - Qualitative techniques to investigate how patients evaluate dentists: a pilot
      study.
AB  - OBJECTIVES: Most previous studies have portrayed patient satisfaction as a rather
      simple outcome based solely on patient perceptions. The goal of this pilot study
      was to determine if evidence could be found to support the view that patient
      evaluation is a more complex process better explained by drawing on the theories
      of 'disconfirmation of expectations' and 'attribution'. METHODS: A qualitative
      methodological approach was chosen with data collection being achieved by means
      of four focus group interviews comprising a total of 25 participants (16 women
      and 9 men, mean age 43.8 years, standard deviation of 14.45) representing a wider
      population of adults (over the age of 18) who had attended for dental treatment
      within the previous 12 months. RESULTS: Analysis suggests that patient
      perceptions of dental practice alone do not fully account for the way patients
      evaluate dentists. Disconfirmation of expectations does take place during the
      evaluation process. Equally, patients appear to apply the attributional concepts
      of 'duty' and 'culpability' to determine either satisfaction or dissatisfaction.
      CONCLUSIONS: A better understanding of patient satisfaction, and the evaluation
      process that leads to satisfaction, can only be achieved if, in addition to
      patient perceptions, other antecedent factors such as patient expectations and
      desires are considered. Disconfirmation and attribution theory do appear to play
      an important role in this process and warrant further investigation.

PMID- 10901405
TI  - Surveillance of primary dentition caries in Germiston, South Africa, 1981-97.
AB  - OBJECTIVE: This 17-year-long study examined trends of dental caries rates in the
      primary dentition of 6843 preschool children in a South African city. METHODS:
      Calibrated dentists did repeated cross-sectional epidemiological surveys of
      dental caries in 2- to 5-year-old nursery school children using WHO diagnostic
      criteria between 1981 and 1997. RESULTS: Both the percentage of children with
      dmft>0 and mean dmft increased between 1981 and 1989 and have slowly declined
      ever since in the absence of organised prevention to produce a secular trend of
      decreasing caries rates. The dt/dmft percentage ranged between 60% and 100%
      except in 1991 when it dropped to 40% and the ft/dmft percentage component rose
      proportionally, probably due to an economic effect. CONCLUSIONS: The percentage
      of children with dmft>0 and mean dmft decreased over the study period at all
      ages, the reason for which is unknown but is speculated to be due to a change in
      mutans streptococci strains.

PMID- 10901406
TI  - The efficiency of the community dental service in England: a data envelopment
      analysis.
AB  - OBJECTIVES: To assess the efficiency with which health authorities' Community
      Dental Services provide dental care in England. METHODS: A data envelopment
      analysis of inputs (hours worked by dental officers, therapists, hygienists and
      others) and outputs (screening, treatment, prevention) of the Community Dental
      Service (CDS) was conducted. Relative efficiency ratings of the CDS by health
      authority were further analysed in order to identify external factors which
      effect efficiency and are outside the control of the Community Dental Service.
      RESULTS: The relative efficiency of the CDS varies widely in England--on average
      the CDS is operating at 75% of efficient levels compared to best-practice
      services. This could not be explained by plausible factors outside the CDS's
      control, such as differences in deprivation and urban-rural differences between
      health authorities. CONCLUSIONS: These results, if validated by further studies,
      should be disturbing since many Community Dental Services services appear to be
      under-performing. However, this data-driven study could not uncover the detailed
      context of an individual service's performance. A useful next step would be
      detailed case-studies of several "star" and under-performing services to search
      for deeper reasons underpinning relative performance levels.

PMID- 10901407
TI  - Caries in the primary dentition, after discontinuation of water fluoridation,
      among children receiving comprehensive dental care.
AB  - The city of Kuopio in central Finland had fluoridated piped water for 33 years,
      beginning in 1959. Due to strong opposition by various civic groups, water
      fluoridation was stopped at the end of 1992. There is little information on the
      consequences of stopping fluoridation in a community with comprehensive dental
      care for all children and adolescents, who are frequently exposed to different
      fluoride measures both at home and in the dental office. OBJECTIVES: The aim of
      this repeated cross-sectional survey was to examine how discontinuation of water
      fluoridation in Kuopio affected caries in the primary dentition. Changes in the
      mean dmfs values between 1992 and 1995 in Kuopio were compared to those in
      Jyvaskyla, a low-fluoride community that has repeatedly been used as the
      reference area for Kuopio. METHODS: In 1992 and 1995, independent random samples
      of all children aged 3, 6 and 9 years were drawn in Kuopio and Jyvaskyla. The
      total number of subjects examined was 421 in 1992 and 894 in 1995. Calibrated
      dentists registered caries clinically and radiographically. RESULTS: In all age
      groups both in 1992 and 1995, the point estimates for mean dmfs values were lower
      in the non-fluoridated town. In both towns, the observed mean dmfs values were
      smaller in 1995 than in 1992. CONCLUSION: Despite discontinuation of water
      fluoridation, no increase of caries frequency in primary teeth was observed in
      Kuopio within a three-year period.

PMID- 10901408
TI  - Incidence of dental anxiety in young adults in relation to dental treatment
      experience.
AB  - OBJECTIVES: To document the incidence of dental anxiety among individuals aged 18
      years at baseline and 26 years at follow-up, and to determine if dental treatment
      experience continues to play a significant etiological role with respect to the
      onset of dental anxiety in young adults. METHODS: Dental anxiety scale (DAS;
      Corah, 1969) scores at ages 15, 18 and 26 were obtained for Study members in the
      Dunedin Multidisciplinary Health and Development Study. Dental examinations were
      conducted, and sociodemographic and dental service-use data were collected using
      a self-report questionnaire. Using a case definition of a DAS score of 13 or
      more, age 18-26 incident cases were identified and their dental treatment
      experience and service-use characteristics compared with the remainder. RESULTS:
      DAS scores at 18 and 26 were available for 792 (80.8%) of the 980 26-year-old
      Study members. An increase in dental anxiety prevalence was observed over the
      eight-year period, with an annualized incidence of 2.1%. Fewer incident cases had
      visited a dentist in the previous eight years, and there were no differences
      between incident cases and others in their eight-year DFS, FS or tooth-loss
      increments. A subgroup of "recurrent" cases was identified who were dentally
      anxious at 15 and 26 but not at 18, and their eight-year incidence of tooth loss
      due to caries was substantially higher than non-cases. CONCLUSIONS: Aversive
      conditioning experiences appear to be unrelated to the adult onset of dental
      anxiety, and it may be that particular temperamental or psychological traits are
      associated with the condition.

PMID- 10901409
TI  - Dental caries and its relationship to bacterial infection, hypoplasia, diet, and
      oral hygiene in 6- to 36-month-old children.
AB  - Caufield et al. (1) have suggested that the acquisition of mutans streptococci in
      young children most likely takes place during a "window of infectivity" from 19
      to 31 months of age. OBJECTIVES AND METHODS: This study determined the prevalence
      of dental caries and bacterial infection in a randomly selected sample of 199
      children 6 to 36 months old from the island of Saipan in the Common-wealth of the
      Northern Mariana Islands, USA. The relationships between caries and Streptococcus
      mutans infection, hypoplasia, diet and oral hygiene behavior were investigated.
      RESULTS AND CONCLUSIONS: The overall estimated prevalence of caries was high:
      46.8% of the children had white spot lesions and 39.1% had enamel cavitation.
      Colonization was seen in very young children; S. mutans was detected in 25% of
      the predentate children. The results of multi-variable modeling support the
      hypothesis that bacterial infection, diet, and hypoplasia are important in the
      etiology of dental caries in this population. Adjusted for age and ethnicity,
      children with a high level of S. mutans detected were 5 times more likely to have
      dental caries than children with a lower level of S. mutans detected. Hypoplasia
      and a high cariogenicity score (diet) were also significant independent
      predictors. The odds of having any white spot lesions or enamel cavitation were
      9.6 times greater for children with any hypoplasia, and 7.8 times greater for
      children with high cariogenicity scores relative to those with lower scores after
      adjusting for level of S. mutans, age and ethnicity. Sleeping with a bottle,
      maternal sharing of utensils, and high snacking frequency were not significant
      predictors of caries in this population.

PMID- 10901410
TI  - Dental caries and sugar intake of children from rural areas with different water
      fluoride levels in Paraiba, Brazil.
AB  - Few reports have investigated caries prevalence in rural areas of Brazil.
      OBJECTIVE: The aim of this study was to observe the caries prevalence (DMFT,
      DMFS) in 12-year-old children living in rural villages of Paraiba, Brazil with
      low and moderate fluoride levels in the drinking water and to relate it to sugar
      intake and oral hygiene. METHODS: One hundred and ninety four children from 13
      villages were grouped according to the water fluoride levels: low fluoride (LF,
      <0.2 ppm F, 96 children) and moderate fluoride (MF, 0.7-1.0 ppm F, 98 children).
      Caries and oral hygiene (OHI-S) were scored according to WHO criteria. Sugar
      intake was assessed through interviews. A sub-set of subjects (n=23) from the LF
      group was re-examined 2 years later. RESULTS: For the LF and MF groups the DMFT
      (mean, SD) observed was 3.9 (3.7) and 2.5 (2.1) respectively, the DMFS was 9.2
      (10.6) and 5.4 (5.7). Both indexes (DMFT, DMFS) showed significant differences
      (P<0.01, Mann-Whitney U-test) according to the fluoride levels in the drinking
      water. The mean increment of caries in the sub-set group of subjects was
      approximately 1.5 surfaces per subject/year. The reported sugar intake was low
      for both water fluoride groups (P>0.05). In a regression analysis the water
      fluoride levels, the use of fluoridated toothpaste and oral hygiene index were
      related to DMFS (R2=0.08, P< or =0.05). CONCLUSIONS: Caries prevalence was lower
      in MF than in LF rural areas of Paraiba. Caries and sugar intake seems to be
      lower in rural areas than in urban areas of Paraiba with similar fluoride levels
      in the drinking water.

PMID- 10901412
TI  - Theory of solid-phase microextraction
AB  - The main objective of this contribution is to describe the fundamental concepts
      associated with solid-phase microextraction (SPME). Theory provides insight when
      developing SPME methods and identifies parameters for rigorous control and
      optimization. A mathematical model has been developed to understand the principal
      processes of SPME by applying basic fundamental principles of thermodynamics and
      diffusion theory. The model assumes idealized conditions and is limited to air,
      liquid, or headspace above liquid sampling. Theory for ideal cases can be quite
      accurate for trace concentrations in simple matrices such as air or drinking
      water at ambient conditions when secondary factors such as thermal expansion of
      polymers and changes in diffusion coefficients because of solutes in polymers can
      be neglected. When conditions are more complex, theory for ideal cases still
      efficiently estimates general relationships between parameters.

PMID- 10901411
TI  - ART restorations and sealants placed in Chinese school children--results after
      three years.
AB  - OBJECTIVES: These were to assess whether ART restorations and sealants could be
      provided to children in a school environment in China, to assess patient
      acceptability of the ART approach, and to evaluate on a longitudinal basis the
      treatments performed. METHODS: This study was conducted in Deyang, Sichuan
      Province, in western China. A total of 294 ART restorations were placed in 197
      children and 191 fissure sealants were placed in 140 children by five middle
      level dentists in four secondary schools. Standard instruments and procedures for
      ART were used. The restorative material used was a high-strength glass-ionomer
      (Ketac-Molar, ESPE). The treatments were evaluated annually after placement by
      the same examiner who had not been involved in the placement of the restorations
      nor sealants using explorers and mouth-mirrors. At the 3-year examination an
      independent external examiner evaluated the restorations using USPHS criteria.
      RESULTS: Most of the children did not report discomfort during treatment and 92%
      were willing to receive ART restorations again. The cumulative 1-year and 3-year
      survival rates of small Class I restorations were 99% and 92% respectively. The
      corresponding figures for large Class I restorations were 90% and 77%. After 3
      years, 72% of the sealants were either partially or completely retained. Only 2%
      of the sealed teeth developed fissure caries and these involved teeth where the
      sealants had been lost. Similar success rates were found using USPHS criteria.
      CONCLUSIONS: The ART approach for preventing and treating tooth decay in Chinese
      school children was shown to be appropriate, effective and acceptable. The 3-year
      survival rates of the restorations were high but were related to the size and
      type of the restoration.

PMID- 10901413
TI  - Optimization of extraction conditions and fiber selection for semivolatile
      analytes using solid-phase microextraction
AB  - A group of 15 large volatile and semivolatile analytes (MW 92-499 amu)
      representing 13 organic classes are extracted with 9 different solid-phase
      microextraction fibers. The extraction efficiencies of the fibers for each of the
      analytes are compared. The influence of modifying the pH of the sample on the
      extraction efficiency of the fibers is shown. The effects of the size of the
      analytes with respect to fiber coating thickness and the relationship between
      fiber coating polarity and analyte polarity are discussed. In addition to fiber
      polarity and coating thickness, the different mechanisms by which the fibers
      extract are presented. A comparison of immersion and heated headspace extraction
      techniques for these analytes is shown.

PMID- 10901414
TI  - Using microwave distillation-solid-phase microextraction--gas chromatography-
      mass spectrometry for analyzing fish tissue.
AB  - A technique for the analysis of the volatile compounds from fish tissue employing
      microwave distillation-solid-phase microextraction-gas chromatography-mass
      spectrometry is described. A qualitative listing of 174 compounds observed in the
      headspace is given, and a quantitative method for the determination of the off
      flavor contaminants (2-methylisoborneol and geosmin) is presented. Borneol and
      decahydro-1-naphthol are used as the surrogate and internal standards,
      respectively. A linear calibration curve is obtained for 0.1 to 5 ppb with a
      recovery level of 60% at 2.5 ppb. Comparison of the instrumental method with a
      human flavor checker showed good agreement.

PMID- 10901415
TI  - The use of solid-phase microextraction--gas chromatography in forensic analysis.
AB  - A thorough review of the application of solid-phase microextraction (SPME)
      combined with gas chromatography for the analysis of forensic specimens is
      presented, including experimental results for several recent applications. The
      SPME applications covered in this comprehensive review include ignitable liquid
      residues (also referred to as accelerants), explosive traces, drugs and poisons
      from biological specimens, and other forensic applications. Recently developed
      SPME methods are also presented, including the analysis of ignitable liquid
      residues on human skin, odor signatures, and several drug applications such as
      free-fraction antipsychotic drug levels, blood alcohol casework, drink-tampering
      analysis, and gamma-hydroxybutyrate identification without the need for
      derivatization. SPME is shown to be an inexpensive, rapid, and sensitive method
      for the analysis of a variety of forensic specimens.

PMID- 10901416
TI  - Determination of major aroma impact compounds in fermented cucumbers by solid
      phase microextraction--gas chromatography--mass spectrometry--olfactometry
      detection.
AB  - Purge-and-trap, solid-phase extraction, and solid-phase microextraction-gas
      chromatography-mass spectrometry (SPME-GC-MS) sample preparation techniques for
      the analysis of odor impact chemicals in fermented cucumber brine are compared.
      SPME-GC-MS is coupled with detection frequency olfactometry experiments to
      determine key impact odor compounds in the brine. The most potent odorants that
      define the typical characteristic brine aroma are trans-4-hexenoic acid and cis-4
      hexenoic acid. Confirmation of key impact odorants in brine is confirmed by
      recombination experiments.

PMID- 10901417
TI  - Solid-phase microextraction method for the quantitative analysis of styrene in
      water.
AB  - A headspace solid-phase microextraction (HS-SPME) method is developed for the
      determination of styrene in drinking water. Gas chromatography (GC)-mass
      spectrometry is utilized for qualitative analysis. A manual SPME holder with 85
      microm polyacrylate coating is used to extract the styrene from water, which is
      determined to have good linearity (correlation coefficient r = 0.9999 for 1.00
      100.00 microg/L range), a relative standard deviation of 1.9%, and a detection
      limit of 0.30 microg/L. This method is compared with a classical headspace GC
      method.

PMID- 10901418
TI  - Alterations in 3-hydroxy-3-methylglutaryl-CoA reductase mRNA concentration in
      cultured chick aortic smooth muscle cells.
AB  - We observed and compared alterations in 3-hydroxy-3-methylglutaryl (HMG)-CoA
      reductase at the transcriptional level in unsynchronized, three-passage cultures
      of smooth-muscle cells from the aorta of chicks fed on a control diet (C-SMC) and
      those of chicks fed on a similar diet plus cholesterol (Ch-SMC). Alterations in
      reductase mRNA concentrations in senescent cultures were much lower. We used a
      modification of the competitive (c) reverse transcription polymerase chain
      reaction method, using a Thermus thermophilus DNA polymerase (Tth pol) to
      quantify the very scarce species of HMG-CoA reductase mRNA in samples of
      cytoplasmic SMC mRNA. We cloned and sequenced a 199 bp cDNA fragment of chicken
      HMG-CoA reductase, which encoded a region of 66 amino acids belonging to the
      catalytic domain of the enzyme. HMG-CoA reductase mRNA concentrations from young
      C-SMC cultures rose 3.89-fold 4 h after the change of medium and returned to base
      levels between 8 to 12 h afterward. Concentrations in Ch-SMC cultures increased
      less (2.36-fold) 8 h after the change to fresh medium. Increases in reductase
      mRNA in senescent cultures of Ch-SMC and C-SMC measured under similar conditions
      were only 1.28- and 1.39-fold, respectively.

PMID- 10901420
TI  - Dietary cod liver oil decreases arachidonic acid in rat gastric mucosa and
      increases stress-induced gastric erosions.
AB  - The purpose of this study was to examine the influence of long-term feeding of
      dietary fat rich in either n-3 or n-6 fatty acids on the availability of
      arachidonic acid (20:4n-6) in major phospholipids of gastric mucosa in rats.
      Three groups of male Wistar rats were fed either a standard diet, a cod liver oil
      enriched diet (10% by weight), or a corn oil-enriched diet (10% by weight) for 8
      mon. Dietary cod liver oil significantly reduced the level of 20:4n-6 in
      phosphatidylcholine (PC) and in phosphatidylethanolamine (PE) of gastric mucosa.
      The loss of 20:4n-6 was compensated for by eicosapentaenoic acid (20:5n-3) in PC,
      whereas the decrease in 20:4n-6 in PE corresponded to the increase in three n-3
      fatty acids: 20:5n-3, docosapentaenoic acid (22:5n-3), and docosahexaenoic acid
      (22:6n-3). The level of 20:5n-3 was higher than the level of 22:6n-3 both in PC
      and PE of mucosa in rats fed cod liver oil. Diets supplemented with corn oil
      increased the level of 18:2n-6 but decreased the monoene fatty acids 16:1 and
      18:1n-7 in PC but not in PE of gastric mucosa. The 20:4n-6 levels of both PC and
      PE were markedly reduced by dietary cod liver oil, to about one-third of control
      levels. Similar changes were also observed in the stomach wall. Gastric erosions
      were observed in all rats exposed to restriction stress, but this form of stress
      induced twice the number of erosions in rats fed fish oil compared to control
      rats or rats fed corn oil. We conclude that a diet rich in fish oil altered the
      balance between n-6 and n-3 fatty acids in major gastric mucosal phospholipids,
      markedly reduced the availability of 20:4n-6, and increased the incidence of
      gastric erosions induced by restriction or emotional stress.

PMID- 10901419
TI  - Membrane physical properties do not explain increased cyclic AMP production in
      hepatocytes from rats fed menhaden oil.
AB  - To study the effect of altering plasma membrane fatty acid composition on the
      glucagon signal transduction pathway, cAMP accumulation was measured in
      hepatocytes from rats fed diets containing either menhaden oil (MO) or coconut
      oil (CO). Hepatocytes from MO-fed animals produced significantly more cAMP in
      response to glucagon and forskolin compared to CO-fed animals. Glucagon receptor
      number and affinity were similar in MO- and CO-fed rats. Liver plasma membranes
      from MO-fed animals were enriched in long-chain n-3 fatty acids and contained
      significantly lower amounts of saturated C10-C16 and 18:1n-9 than CO-fed animals.
      Membrane physical properties were examined using both Fourier transform infrared
      spectroscopy (FTIR) and the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene
      (DPH). FTIR analysis revealed that below 34 degrees C, CO membranes were more
      ordered than MO membranes. However, as assay temperature approached 37 degrees C,
      MO and CO membranes became similarly ordered. DPH polarization values indicated
      no differences in membrane order at 37 degrees C, whereas membrane order was
      decreased in CO-fed animals at 25 degrees C. These data indicate the importance
      of assay temperature in assessing the influence of membrane physical properties
      on the activity of signal transduction pathways. Whereas increased signal
      transduction activity has been correlated to reduced membrane order in MO-fed
      animals, these data indicate that at physiological temperatures membrane order
      did not vary between groups. Enhanced cAMP accumulation in response to forskolin
      indicates that adenylate cyclase activity or content may be elevated in MO- vs.
      CO-fed rats. Enhanced adenylate cyclase activity may result, in part, from
      changes in specific fatty acids in hepatocyte plasma membranes without
      demonstrable changes in membrane physical properties.

PMID- 10901421
TI  - Low erucic acid canola oil does not induce heart triglyceride accumulation in
      neonatal pigs fed formula.
AB  - Canola oil is not approved for use in infant formula largely because of concerns
      over possible accumulation of triglyceride in heart as a result of the small
      amounts of erucic acid (22:1n-9) in the oil. Therefore, the concentration and
      composition of heart triglyceride were determined in piglets fed from birth for
      10 (n = 4-6) or 18 (n = 6) d with formula containing about 50% energy fat as 100%
      canola oil (0.5% 22:1n-9) or 100% soybean oil, or 26% canola oil or soy oil
      (blend) with palm, high-oleic sunflower and coconut oil, providing amounts of
      16:0 and 18:1 closer to milk, or a mix of soy, high-oleic sunflower and flaxseed
      oils with C16 and C18 fatty acids similar to canola oil but without 22:1.
      Biochemical analysis found no differences in heart triglyceride concentrations
      among the groups at 10 or 18 d. Assessment of heart triglycerides using Oil Red O
      staining in select treatments confirmed no differences between 10-d-old piglets
      fed formula with 100% canola oil (n = 4), 100% soy oil (n = 4), or the soy oil
      blend (n = 2). Levels of 22:1n-9 in heart triglyceride and phospholipid, however,
      were higher (P<0.01) in piglets fed 100% canola oil or the canola oil blend, with
      higher levels found in triglycerides compared with phospholipids. The modest
      accumulation of 22:1n-9 associated with feeding canola oil was not associated
      with biochemical evidence of heart triglyceride accumulation at 10 and 18 d.

PMID- 10901423
TI  - Cholesterol vehicle in experimental atherosclerosis. 23. Effects of specific
      synthetic triglycerides.
AB  - Earlier work has shown that increasing concentration of palmitic acid at the sn-2
      position of a fat enhances the atherogenic properties of that fat. This effect
      has been observed with lard, tallow, cottonseed oil, and palm oil. In the
      experiment reported here, we have studied the atherogenic effects of four
      synthetic fats fed to rabbits as 58% (w/w) of the total fat (15%) (w/w) of a
      semipurified diet containing 0.05% cholesterol. The fats being tested were: 1,3
      stearoyl-2-oleoylglycerol (SOS); 1,2-stearoyl-3-oleoylglycerol (SSO); 1,3
      palmitoyl-2-oleoylglycerol (POP); and 1,2-palmitoyl-3-oleoylglycerol (PPO). After
      20 wk on diet there were no differences among the groups in weight gain, liver
      weight, serum, or liver lipids. These data are consistent with our previous
      findings. There were significant differences in atherosclerosis. The most severe
      atherosclerosis was observed in group PPO and the least in groups SSO and POP.
      Severity of atherosclerosis was graded visually on a 0-4 scale. The average
      atherosclerosis [(aortic arch and thoracic aorta) divided by 2] was: SOS--1.35;
      SSO--0.97; POP--0.83; and PPO--1.80. Fecal fat excretion (an indicator of fat
      absorption) was higher in the two groups fed the stearic acid-rich fats and lower
      in groups fed the palmitic acid-rich fats. There were no differences in low
      density lipoprotein particle size. The results confirm previous findings
      concerning the increased atherogenicity of fats bearing palmitic acid at the sn-2
      position. The mechanism underlying these observations is moot but may, in part,
      reflect greater absorption of the atherogenic fat.

PMID- 10901422
TI  - Dehydroepiandrosterone alters lipid profiles in Zucker rats.
AB  - High free fatty acid (FFA) levels are common in obesity and in diseases such as
      diabetes that are associated with the obese state. Dehydroepiandrosterone (DHEA)
      decreases dietary fat consumption, body fat content, and insulin levels in the
      obese Zucker rat (ZR), a genetic model of human youth-onset obesity and type 2
      diabetes mellitus. This study was conducted to investigate the effects of DHEA on
      lean and obese ZR serum, adipose, and hepatic tissue fatty acid (FA) profiles and
      serum FFA levels. Because DHEA is known to decrease fat consumption and body fat,
      we postulate that DHEA may also alter FA profiles and FFA levels of the obese ZR
      such that they more closely resemble the profiles and levels of their lean
      siblings. In this study there was a DHEA and a pair-fed (PF) group (n = 6) for 12
      lean and 12 obese ZR. The diet of the treatment groups was supplemented with 0.6%
      DHEA, and PF groups were given the same average calories consumed by their
      corresponding DHEA group for 30 d. Fasted animals were sacrificed, and FA
      profiles and FFA levels were measured. Serum FFA levels were higher in obese
      (approximately 1 mmol/L) compared to lean rats (approximately 0.6 mmol/L). After
      30 d of DHEA treatment, FFA levels were lower (P < 0.05) in both lean and obese
      groups. Although several significant differences in FA profile of serum, hepatic,
      and adipose lipid components were observed between lean and obese ZR, DHEA
      related changes were only observed in the serum phospholipid (PL) and liver PL
      and triglyceride fractions. The slight but significant decrease in serum FFA
      levels may be reflected by changes in serum PL FA profiles. Specific hepatic FA
      profile alterations may be related to DHEA's known effects in inducing hepatic
      peroxisomes. We speculate that such FA changes may give insight into a mechanism
      for the action of DHEA.

PMID- 10901424
TI  - L-Carnitine effects on chemical composition of plasma lipoproteins of rabbits fed
      with normal and high cholesterol diets.
AB  - L-Carnitine plays an important role in the mitochondrial uptake of long-chain
      fatty acids in mammals. It has recently been shown that this compound has a
      marked hypo-cholesterolemic effect when used in conjunction with lipid-rich
      diets. The aim of this study was to investigate the effects of L-carnitine on the
      fatty acid composition of plasma lipoproteins in rabbits fed with different
      diets. Four different groups were investigated: group I (standard diet), group II
      (standard diet supplemented with L-carnitine at 80 mg/kg), group III (standard
      diet supplemented with 0.5% cholesterol), and group IV (standard diet
      supplemented with 0.5% cholesterol plus L-carnitine at 80 mg/kg). The feeding
      period was 126 d. Total plasma cholesterol was indistinguishable in groups I and
      II, but increased nearly 40-fold in group III. This increment was reduced by 50%
      in group IV. Correspondingly, total cholesterol content in lipoprotein fractions
      [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density
      lipoprotein (HDL) separated by agarose gel chromatography was the same for groups
      I and II, while for animals fed a cholesterol-rich diet (III) total cholesterol
      in VLDL + LDL increased nearly 100-fold when compared with groups I and II but,
      again, the increment was reduced by 50% in group IV. In contrast, total
      cholesterol in HDL increased only fivefold for both groups III and IV when
      compared with groups I and II, indicating no effects of L-carnitine on this
      parameter. The reduction of total cholesterol in VLDL + LDL particles in animals
      fed a cholesterol-rich diet plus L-carnitine was associated with a marked
      decrease in the ratio of cholesteryl ester to free cholesterol and a dramatic
      increase in their phospholipid content; opposite effects were observed for HDL. L
      Carnitine induced a marked decrease in the saturated to unsaturated C16 + C18
      fatty acid ratio in cholesteryl esters associated with VLDL and LDL from animals
      fed with both normal and cholesterol-rich diets. The opposite effect (a large
      increase in the saturated to unsaturated fatty acid ratio) was observed for both
      cholesteryl esters and phospholipids associated with HDL in animals fed with both
      diets. The results suggested that the hypocholesterolemic effects of L-carnitine
      could be associated with increased systemic breakdown of cholesteryl esters, a
      probable increase in reverse cholesterol transport, and the stabilization of a
      phospholipid-based structure of VLDL + LDL particles.

PMID- 10901425
TI  - Protective effect of olive oil and its phenolic compounds against low density
      lipoprotein oxidation.
AB  - The protective effect of phenolic compounds from an olive oil extract, and of
      olive oils with (extra-virgin) and without (refined) phenolic components, on low
      density lipoprotein (LDL) oxidation was investigated. When added to isolated LDL,
      phenolics [0.025-0.3 mg/L caffeic acid equivalents (CAE)] increased the lag time
      of conjugated diene formation after copper-mediated LDL oxidation in a
      concentration-dependent manner. Concentrations of phenolics greater than 20 mg/L
      inhibited formation of thiobarbituric-acid reactive substances after AAPH
      initiated LDL oxidation. LDL isolated from plasma after preincubation with
      phenolics (25-160 mg/L CAE) showed a concentration-dependent increase in the lag
      time of conjugated diene formation after copper-mediated LDL oxidation. Refined
      olive oil (0 mg/L CAE) and extra-virgin olive oil (0.1 and 0.3 mg/L CAE) added to
      isolated LDL caused an increase in the lag time of conjugated diene formation
      after copper-mediated LDL oxidation that was related to olive oil phenolic
      content. Multiple regression analysis showed that phenolics were significantly
      associated with the increase in lag time after adjustment for effects of other
      antioxidants; alpha-tocopherol also achieved a statistically significant effect.
      These results indicate that olive oil phenolic compounds protect LDL against
      peroxyl radical-dependent and metal-induced oxidation in vitro and could
      associate with LDL after their incubation with plasma. Both types of olive oil
      protect LDL from oxidation. Olive oil containing phenolics, however, shows more
      antioxidant effect on LDL oxidation than refined olive oil.

PMID- 10901426
TI  - Composition of cecal bile acids in ex-germfree mice inoculated with human
      intestinal bacteria.
AB  - Germfree (GF) mice were orally inoculated with human fecal suspension or various
      components of human fecal microbiota. Three weeks after the inoculation, cecal
      bile acid composition of these mice was examined. More than 80% of total bile
      acids was deconjugated in the cecal contents of ex-GF mice associated with human
      fecal dilutions of 10(-2) or 10(-6), or anaerobic growth from a dilution of 10(
      6). In these ex-GF mice, deoxycholic acid accounted for about 20% of total bile
      acids. In the cecal contents of ex-GF mice associated only with clostridia,
      unconjugated bile acids made up less than 40% of total bile acids, about half of
      those in other ex-GF groups. However, the percentage of deoxycholic acid in these
      mice was the same as that in the other groups. These results indicate that
      dominant anaerobic bacterial combination is efficient for deconjugation of
      primary bile acids, and that clostridia in the human feces may play an important
      role in 7alpha-dehydroxylation of unconjugated primary bile acids in the
      intestine.

PMID- 10901427
TI  - Lipid and fatty acid composition and energy partitioning during embryo
      development in the shrimp Macrobrachium borellii.
AB  - Energy partitioning, composition of lipids and fatty acids, and their utilization
      by embryos were determined in the lecithotrophic shrimp Macrobrachium borellii
      during seven development stages. The biochemical composition at stage I is
      represented by lipids, proteins, and carbohydrates, with 29.3, 28.7, and 0.2% dry
      weight, respectively. The former two were identified as the major energy
      providing components, contributing 131 and 60 cal/100 mg egg, dry weight,
      respectively. The overall conversion efficiency (CE) was 45.0% (calculated as
      percentage of vitelline energy transformed into embryonic tissues). Lipids were
      the most important energy reserve (CE 39.3%), followed by proteins (CE 57.1%),
      both being simultaneously utilized during development while carbohydrates were
      synthesized de novo (CE 587.5%). Variation in the lipid class composition of
      embryos and vitellus showed an accumulation of triacylglycerols (TAG) and
      phospholipids (PL) up to stage IV, a more active accumulation and selective
      utilization phase (stages V and VI), and a consumption and de novo synthesis
      period until hatching. Structural lipids (PL and cholesterol) and pigment
      astaxanthin were selectively conserved in embryos, but TAG, hydrocarbons, and
      esterified sterols were preferentially depleted. Monounsaturated fatty acids (FA)
      were the major group in TAG, whereas polyunsaturated FA (PUFA) were the major
      group in PL after organogenesis. Certain PUFA such as 22:6n-3 and 20:5n-3 were
      selectively accumulated in PL.

PMID- 10901428
TI  - Lipid metabolism and tissue composition in Atlantic salmon (Salmo salar L.)-
      effects of capelin oil, palm oil, and oleic acid-enriched sunflower oil as
      dietary lipid sources.
AB  - Triplicate groups of Atlantic salmon (Salmo salar L.) were fed four diets
      containing different oils as the sole lipid source, i.e., capelin oil, oleic acid
      enriched sunflower oil, a 1:1 (w/w) mixture of capelin oil and oleic acid
      enriched sunflower oil, and palm oil (PO). The beta-oxidation capacity, protein
      utilization, digestibility of dietary fatty acids and fatty acid composition of
      lipoproteins, plasma, liver, belly flap, red and white muscle were measured.
      Further, the lipid class and protein levels in the lipoproteins were analyzed.
      The different dietary fatty acid compositions did not significantly affect
      protein utilization or beta-oxidation capacity in red muscle. The levels of total
      cholesterol, triacylglycerols, and protein in very low density lipoprotein
      (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), and plasma
      were not significantly affected by the dietary fatty acids. VLDL, LDL, and HDL
      fatty acid compositions were decreasingly affected by dietary fatty acid
      composition. Dietary fatty acid composition significantly affected both the
      relative fatty acid composition and the amount of fatty acids (mg fatty acid per
      g tissue, wet weight) in belly flap, liver, red and white muscle. Apparent
      digestibility of the fatty acids, measured by adding yttrium oxide as inert
      marker, was significantly lower in fish fed the PO diet compared to the other
      three diets.

PMID- 10901429
TI  - Evidence for the presence of 1,2-cyclic acetal type sn-glycero-3
      phosphoethanolamines in the sea anemone, Actiniogeton sp.
AB  - Five 1,2-cyclic acetal-type sn-glycero-3-phosphoethanolamines (CGPE) were
      isolated in a pure state from the sea anemone, Actiniogeton sp. (Coelenterata).
      Their structures, including the absolute configurations, have been determined on
      the basis of chemical and spectral data to be so-called Feulgen's
      acetalphosphatides, which have been regarded as artifacts derived from original
      plasmalogens. We examined whether these CGPE are intact constituents in the
      animal tissues and obtained reliable confirmation that CGPE are normally present
      in the sea anemone.

PMID- 10901431
TI  - Quantitative analysis of long-chain trans-monoenes originating from hydrogenated
      marine oil.
AB  - Gas chromatography (GC) is used for the analysis of trans-fatty acids in
      partially hydrogenated vegetable oils. Although trans-isomers of C18 carbon
      length predominate in partially hydrogenated vegetable oils, trans-isomers of C20
      and C22 carbon length occur in partially hydrogenated fish oil. We report a
      simple silver ion chromatographic combined with capillary GC technique for
      quantitative analysis of trans-monoenes derived from partially hydrogenated fish
      oil. Silver nitrate thin-layer chromatographic (TLC) plates are developed in
      toluene/hexane (50:50, vol/vol). Fatty acid methyl esters are separated into
      saturates (Rf 0.79), trans-monoenes (Rf 0.49), cis-monoenes (Rf 0.27), dienes (Rf
      0.10), and polyunsaturated fatty acids with three or more double bonds remaining
      at the origin. The isolated trans-monoenes are quantitatively analyzed by
      capillary GC. The technique of argentation TLC with GC analysis of isolated
      methyl esters is highly reproducible with 4.8% variation (i.e., coefficient of
      variation, CV%) in R. values and 4.3 and 6.9% CV% in quantification within batch
      and between batch, respectively. Furthermore, the combined technique revealed
      that direct GC analysis underestimated the trans-content of margarines by at
      least 30%. In this study, C20 and C22 trans-monoenes were found in relatively
      large quantities; 13.9% (range 10.3-19.6%) and 7.5% (range 5.3-11.5%),
      respectively, in margarine purchased in 1995, but these C20 and C22 trans
      monoenes were much reduced (0.1%) in a fresh selection of margarine purchased in
      1998. Compositional data from labels underestimated the trans-content of
      margarines, especially those derived from hydrogenated marine oil. Low levels of
      C20 transmonoenes (range 0.1-0.3%) and C22 trans-monoenes (range 0.0-0.1%) were
      identified in adipose tissue obtained from healthy volunteers in 1995, presumably
      indicating consumption of partially hydrogenated fish oil.

PMID- 10901430
TI  - Preparation of functional liposomes with peptide ligands and their binding to
      cell membranes.
AB  - Two novel lipopeptides, which have the peptide ligands [alpha-melanocyte
      stimulating hormone (alpha-MSH)] sequence and repeated [Gly-Arg-Gly-Asp-Se
      (GRGDS) sequence], are designed, synthesized by the solid-phase method, and
      introduced into liposome membranes by the freeze-thaw method. These liposomes
      bearing the peptide ligands on their surface are expected to bind to cell
      membranes. We have confirmed that the lipopeptides are introduced into liposome
      membranes almost quantitatively, while such a high degree of incorporation has
      not been accomplished in conventional methods. In this respect, the present
      method is superior to prepare surface-modified liposomes that are applicable to
      drug carriers and so on. We have also confirmed by using immunoelectron
      microscopy that the peptide ligands are actually located in an aqueous phase. It
      has been shown by flow cytometry that the liposome bearing alpha-MSH peptide
      ligand binds to B16 cells and the liposome bearing the repeated GRGDS sequence
      binds to NIH3T3 cells.

PMID- 10901432
TI  - Lipid analog with 2-nitrophenol trigger designed for liposome fusion at
      physiological pH.
AB  - A novel lipid analog with two long alkyl (C16) chains, an aspartate skeleton, a
      connecting alkyl (C8) chain, and 2-nitrophenol trigger group is synthesized by an
      efficient synthetic route, which can induce liposome fusion at physiological pH.

PMID- 10901433
TI  - Evaluation of brain long-chain acylcarnitines during cerebral ischemia.
AB  - Concentration and distribution of long-chain acylcarnitines in control microwaved
      and ischemic (decapitated) rat brain were measured by electrospray ionization
      tandem mass spectrometry. The total acylcarnitine concentration from control rat
      brains equaled 7-8 nmol/g wet weight brain, about one-fourth the total
      concentration of long-chain acyl-CoA, indicating a small role in buffering the
      total acyl-CoA pool concentration. Furthermore, acylcarnitine did not differ
      between ischemic and control rat brain with regard to total concentration or
      concentrations of molecular species of acylcarnitine. Therefore, the size of the
      acylcarnitine pool in brain is not affected by the dramatic increase in
      unesterified fatty acids (approximately 4x) that occurs in ischemia.

PMID- 10901434
TI  - Possible redox regulation of sperm motility activation.

PMID- 10901435
TI  - Genetic and cellular analysis of male germ cell development.
AB  - The evolution of the germline has been studied for many decades. Although the
      pathway of germ cell primordial migration and the kinetic evolution of the
      gonocytes are well known, their genetic and cellular controls are poorly
      understood. Recently, a genetic approach using gene knockout and a cellular
      investigation using several germ cell culture models has allowed a better
      understanding of the involvement of several genes and factors in the development
      of germ cells during fetal and neonatal life. Because of the obvious importance
      of the development of primordial germ cells and gonocytes in adult fertility and
      its eventual alteration by toxins or xenobiotics, a better knowledge of these
      interactions appears as an important research area.

PMID- 10901437
TI  - CASA--practical aspects.

PMID- 10901436
TI  - Law and ethics meet: when couples fight over their frozen embryos.

PMID- 10901438
TI  - Effect of 5alpha-dihydrotestosterone implants on the fertility of male rats
      treated with tamoxifen.
AB  - In adult male rats, tamoxifen (TAM) reduces circulating levels of luteinizing
      hormone (LH) and testosterone (T) with no effect on follicle-stimulating hormone
      (FSH) and prolactin (PRL). It reduces the male rat's ability to inseminate the
      female (potency), as well as its siring ability (fecundity). The objective of the
      present study was to test whether androgen supplementation could reverse all or
      some of the observed effects of TAM. To obviate the effects of estrogen, the
      study was designed to evaluate the beneficial or deleterious effect of 5alpha
      dihydrotestosterone (DHT), a 5alpha-reduced, nonaromatizable metabolite of T, on
      the reproductive functions of TAM-treated adult male rats. Adult male rats
      received either saline or TAM (0.2 or 0.4 mg per day p.o.) for 90 days. A group
      of TAM-treated rats was implanted with 6 mg DHT from day 50 to day 90. A third
      group of untreated animals was implanted with 0-, 1-, 3-, or 6-mg DHT implants
      for 90 days. Mating studies were done to assess the fecundity, potency, and
      fertility index at the end of the treatment. Weights of testes, pituitary, and
      accessory sex organs were recorded, and circulating levels of LH, FSH, PRL, T,
      and 17-beta-estradiol were estimated. DHT did not affect the fecundity or
      fertility index. TAM reduced fecundity, potency, and the fertility index. DHT
      implants improved the fertilizing ability of the TAM-treated male rat. This study
      discusses and reviews the role of T and 17-beta-estradiol in sperm-fertilizing
      potential in light of these observations.

PMID- 10901439
TI  - Progesterone-induced calcium influx in cynomolgus monkey (Macaca fascicularis)
      spermatozoa.
AB  - For in vitro capacitation to occur in cynomolgus monkey (Macaca fascicularis)
      spermatozoa, there is an absolute requirement for exogenous stimulation with the
      sperm activators, caffeine (1 mM) and db-cyclic adenosine monophosphate (dbcAMP)
      (1 mM), which are known to induce capacitation-related hyperactivated motility.
      Tyrosine phosphorylation of sperm tail proteins is an integral component of this
      caffeine- and dbcAMP-stimulated hyperactivated motility. In both capacitated and
      noncapacitated human spermatozoa, progesterone (P4) has been reported to elicit
      an immediate, potent increase in intracellular calcium ion concentrations
      [Ca2+]i. The objective of this study was to examine the effects of progesterone
      on requisite events in macaque fertilization, including [Ca2+]i, hyperactivated
      motility, and the concomitant tyrosine phosphorylation of sperm tail (STTP)
      proteins after treatment with caffeine and dbcAMP. The effect of 1 microM of
      progesterone on [Ca2+]i was determined by spectrofluorometry with the fluorescent
      indicator, fura-2/AM, on hyperactivated motility using computer analysis (HTM
      IVOS) with the sorting criteria lateral head amplitude (> or = 8.0 microm),
      curvilinear velocity (> or = 150 microm/s), linearity (< or = 60%), and on STTP
      by immunocytochemistry. The results showed that progesterone elicited a
      significant increase in [Ca2+]i in caffeine- and dbcAMP-activated macaque sperm
      with maximal stimulation at 30 minutes after activation. The response in
      nonactivated sperm was dramatically reduced compared with the response in
      activated sperm. Basal [Ca2+]i increased as a function of time in both activated
      and nonactivated control sperm although basal levels were significantly increased
      in activated sperm. Progesterone stimulation resulted in a small but significant
      increase in both hyperactivation and STTP when sperm were first pretreated with
      caffeine and dbcAMP. Our results provide evidence that macaque sperm activation
      with caffeine and dbcAMP is required for a progesterone-elicited response, which
      results in calcium influx, hyperactivated motility, and sperm tail tyrosine
      phosphorylation.

PMID- 10901440
TI  - Assessment of the acrosomal status of ram spermatozoa by RCA lectin-binding and
      partition in an aqueous two-phase system.
AB  - The acrosome reaction is an important marker for sperm function. Because
      different laboratory techniques may be used to detect this exocytotic process,
      the objective of this study was to investigate the use of fluoresceinated lectins
      to assess the acrosomal status of nonpermeabilized ram spermatozoa. In addition,
      we used centrifugal countercurrent distribution (CCCD) in an aqueous 2-phase
      system to assess the sperm surface modifications associated with the acrosome
      reaction by observing changes in their partition behavior. We analyzed the
      binding of 5-fluorescein isothiocyanate (FITC)-conjugated lectins to ram sperm to
      select a lectin that bound preferentially to the acrosomal region, which would
      allow differentiation of acrosome-intact from acrosome-damaged ram spermatozoa.
      Ricinus communis agglutinin (RCA) bound intensely to the anterior and weakly to
      the equatorial acrosomal regions. Acrosomal labeling changed when spermatozoa
      were induced to acrosome-react with calcium ionophore A23187. RCA acrosomal
      labeling significantly increased (P < .0001) after incubation (84% versus 28% in
      control samples). To determine if RCA lectin labeling could be used to assess the
      acrosomal status of fresh ram spermatozoa in suspension, we compared the
      percentage of acrosome-reacted sperm detected by the carboxyfluorescein
      diacetate/propidium iodide (CFDA/PI) double-fluorescent staining with the
      percentage detected by FITC-RCA labeling. The incidence of acrosome-reacted
      spermatozoa detected by CFDA/PI was not significantly different (P = .704; 13
      comparisons in 6 different experiments) from the incidence of spermatozoa
      detected by FITC-RCA staining. The evaluation of the spontaneous acrosome
      reaction by RCA labeling (5.83%) was not significantly different (P = .644) from
      that assessed by CFDA/PI (6.88%). The percentage of induced acrosome reactions
      detected by CFDA/PI staining (56%) significantly correlated (P < .0001; r =
      0.876) with that detected by RCA labeling (56.67%). We simultaneously carried out
      a comparative CCCD in an aqueous 2-phase system to analyze sperm surface changes
      associated with the acrosome reaction. Results revealed that sperm surface
      hydrophobicity decreased in samples that had been incubated with ionophore
      compared with the untreated-control samples. Likewise, RCA binding after CCCD
      showed that all acrosome-reacted cells were stained, whereas only 42% of cells
      were lectin-labeled in the untreated semen sample. This change in lectin
      reactivity of acrosome-reacted spermatozoa signals the presence of some deep
      membrane or intracellular residues that would affect partitioning. Therefore, the
      FITC-RCA-labeling procedure can be used to accurately assess the acrosomal status
      of ram spermatozoa in suspension.

PMID- 10901441
TI  - Effects of triptorelin, a gonadotropin-releasing hormone agonist, on the human
      prostatic cell lines PC3 and LNCaP.
AB  - Some analogues of gonadotropin-releasing hormone (GnRH) influence the in vitro
      proliferation of cultured human cells by complex interactions that are only
      partially understood. This study explored the effect of Triptorelin, a GnRH
      agonist, on the LNCaP and PC3 prostatic cell lines, which are, respectively,
      responsive and unresponsive to androgen stimulation. The toxicity and cell cycle
      modifications induced by the drug were investigated by FACScan analysis; the
      effect on cell proliferation in different culture conditions was determined by
      counting in a Burker chamber; and the expression of binding sites for 125I
      Triptorelin was revealed by displacement experiments. PC3 cell growth was
      completely unaffected by Triptorelin. The drug caused a double stimulatory
      inhibitory action on the growth of actively proliferating LNCaP cells, depending
      upon the dose and environment. A significant inhibitory effect on proliferation,
      ranging from 25% to 65% compared with controls, was observed at a high dose (10(
      4) M) according to the culture conditions; and a proliferative effect (42%
      compared with controls) was observed at a lower dose (10(-7) M) only in fetal
      bovine serum-supplemented medium. Displacement experiments revealed the
      expression of moderately high affinity and low affinity binding sites in LNCaP
      cells (Kd = 2.6 x 10(-8) and 7.7 x 10(-6) M) but only low affinity binding sites
      in PC3 cells (Kd = 2.7 x 10(-6) M), which suggests that the expression of binding
      sites with different affinity could be associated with a biological response to
      the drug. Proliferation studies in the presence of Cetrorelix, a GnRH antagonist,
      confirmed the different sensitivity of the 2 cell lines to GnRH analogues and
      showed that the proliferative effect of Triptorelin on LNCaP cells can be
      inhibited by the antagonist. Data confirm the cell specificity of Triptorelin's
      action and the peculiarity of its effects on prostatic cell proliferation in our
      experimental conditions.

PMID- 10901442
TI  - Involvement of inhibin in the regulation of follicle-stimulating hormone
      secretion in the young adult male Shiba goat.
AB  - The roles of inhibin and testosterone in the regulation of gonadotropin secretion
      were investigated in young adult male Shiba goats (8-12 months of age). Plasma
      levels of inhibin but not testosterone abruptly decreased after hemicastration
      (75% of the initial level), concomitant with a progressive rise in plasma levels
      of FSH. Removal of the remaining testis at 33 days after the hemicastration
      quickly decreased plasma levels of both inhibin and testosterone and induced a
      progressive increase in plasma FSH and LH. Implantation of testosterone sheets
      immediately after castration suppressed the increase in plasma FSH in part only,
      whereas the increase in LH secretion was almost completely suppressed. An i.v.
      injection of antiserum against [Tyr30] porcine inhibin alpha(1-30) resulted in a
      significant increase in plasma FSH in a dose-dependent manner, without altering
      plasma concentrations of LH. These findings clearly indicate that both inhibin
      and testosterone physiologically regulate FSH secretion and that testosterone is
      the principal gonadal factor regulating LH secretion in the adult male goat.

PMID- 10901443
TI  - Presence of NMDA receptor subunits in the male lower urogenital tract.
AB  - Some sexual responses in the male rat, specifically penile erection, are
      controlled by neural circuits in the brain and spine that are stimulated by the
      binding of excitatory amino acids (EAAs) to the postsynaptic N-methyl-D-aspartate
      receptor (NMDAR). In the hypothalamus, EAA/NMDAR interaction triggers the
      activation of neuronal nitric oxide synthase (nNOS) to produce nitric oxide (NO).
      The local synthesis of this neurotransmitter in the penile nerve terminals causes
      corpora cavernosal relaxation and erection. During sexual activity, NO is assumed
      to participate in seminal emission and ejaculation in the prostate and to inhibit
      voiding reflexes in the bladder. This study aimed to determine in vitro whether
      NMDAR is present in these organs and whether it affects the tone of tissue strips
      through an NO-dependent mechanism. We obtained penile, urinary bladder, and
      ventral prostate tissues from adult male rats and homologous surgical tissues
      from human male patients. We detected the NMDAR protein by Western blot and
      determined the binding of the NMDA antagonist, 3H-CGP. The NMDAR messenger
      ribonucleic acid (mRNA) was detected by reverse transcription/polymerase chain
      reaction and identified by cloning and sequencing. The in vitro response to NMDAR
      antagonists was measured in tissue strips that were precontracted with
      bethanechol or electrical field stimulation (in rat and human bladder),
      phenylephrine (in human corpora cavernosa), or norepinephrine (in human
      prostate). The NMDAR2B protein; ligand-binding activity; and NMDAR1, 2A, and 2B
      mRNAs were detected in all tissues studied. We found an NMDAR1 variant in rat
      prostate and penis and in human prostate that is larger than its cerebellar
      counterpart, but it encodes a 767-amino acid truncated protein (NMDAR1-T). The in
      vitro contraction of tissue strips was inhibited by NMDAR antagonists against the
      following sites: polyamine (with ifenprodil); ion channnel high affinity (with
      dizocilpine); ion channel low affinity (with memantidine, dextrometorphan, and
      ketamine); and, in an NO-independent, nonadrenergic-noncholinergic pathway that
      was only partially affected by EAAs. We conclude that, in vitro, all the
      essential NMDAR subunits are present in the lower urogenital tract, a novel
      variant of subunit 1 is expressed, the tissues bind an NMDAR ligand, and the
      NMDAR antagonists induce relaxation of tissue strips. Further work is necessary
      to determine whether the NMDAR subunits form a fully active receptor and
      participate in the control of organ tone that is relevant to male sexual
      activity.

PMID- 10901444
TI  - Transmembrane versus soluble stem cell factor expression in human testis.
AB  - The interaction between stem cell factor (SCF), a ligand produced by Sertoli
      cells, and its c-kit receptor on germ cells is necessary for successful
      spermatogenesis in animal models. SCF can be alternatively spliced into soluble
      and transmembrane forms, and it is the transmembrane form that is required for
      spermatogenesis in rodents. c-Kit receptors are also present on Leydig cells, and
      soluble SCF has been implicated in the regulation of testosterone production.
      This study had two goals: To test the hypothesis that the extent of germ cell
      production in human males is correlated with the expression of transmembrane SCF,
      and to examine the relationship between testosterone production and the
      expression of soluble SCF in humans. Reverse transcriptase polymerase chain
      reaction was used to determine the ratio of transmembrane-to-soluble SCF in
      testicular tissue. Clinical analysis, hormonal measurements, and histological
      methods were used to evaluate the causes of infertility and to seek correlations
      with the pattern of SCF expression. SCF was preferentially expressed as the
      transmembrane type in all testicular samples, regardless of the state of germ
      cell production. Furthermore, the percent of transmembrane SCF expression was
      independent of clinical and histopathological diagnosis (r(s) = 0.111, n = 28)
      and unrelated to the extent of spermatogenesis. This contrasts with rat models of
      testicular injury that exhibit a decreased proportion of transmembrane SCF with
      atrophy. A significant correlation (r(s) = 0.665, P < .02, n = 16) was found
      between testosterone levels and percent soluble SCF, which suggests that, in
      humans, there may be a regulatory interaction between soluble SCF and
      testosterone.

PMID- 10901445
TI  - Cholesterol inhibitory effects on human sperm-induced acrosome reaction.
AB  - Progesterone (P4) is known to induce an acrosome reaction in mammalian sperm in
      vitro, whereas cholesterol is a major inhibitor of acrosome reaction. This study
      had three objectives: to study the in vitro effects of exogenous cholesterol on
      acrosome reactions in human sperm, to study the mechanism by which cholesterol
      affects P4-induced acrosome reaction and those induced by dibutyryl cyclic
      adenosine monophosphate (db-cAMP), and to study the status of the P4 surface
      receptor during capacitation and acrosome reaction and its relationship with
      cholesterol and different acrosome reaction inducers. Acrosome reaction was
      induced with exposure to 10 microg/mL of P4 for 30 minutes and 1 mM of db-cAMP
      for 30 minutes in motile sperm either in the presence or absence of 0.1-1
      microg/mL of cholesterol for 30 minutes. The effects of a 30-minute exposure to 1
      microg/mL of beta-sitosterol, a cholesterol plant analogue, as well as the
      effects of cholesterol on P4-induced acrosome reactions were compared.
      Fluorescein isothiocyanate-labeled albumin-progesterone conjugate (P4-FITC-BSA)
      was used as the probe in order to quantify the percentage of sperm in which the
      P, surface receptor was exposed. The results of this study indicate that
      cholesterol inhibited P4-induced acrosome reactions when added to the sperm
      during capacitation (long incubation) and when it was added with P4 during the
      induction of acrosome reactions (short incubation). Similarly, acrosome reaction
      that was induced by db-cAMP was also inhibited by cholesterol. Fifty percent of
      P4-induced acrosome reaction was inhibited by a cholesterol concentration of 0.2
      microg/mL. Cholesterol's inhibition of induced acrosome reaction was independent
      of P4 concentration. Beta-sitosterol inhibited P4-induced acrosome reaction in a
      dose-dependent manner that was identical to that of cholesterol. We observed that
      increases in the P4 surface receptor exposure were time-dependent and receptors
      migrated toward the equatorial segment during the first 2 hours of capacitation.
      We also found that db-cAMP induced the appearance of the P4 surface receptor in
      the sperm plasma membrane and that cholesterol inhibited it. The results of this
      study suggest that cholesterol inhibits acrosome reaction in a noncompetitive
      manner by modifying the structure of the sperm plasma membrane, which prevents
      exposure of the P4 surface receptor for P4 binding.

PMID- 10901446
TI  - A problem in need of a solution or technology for its own sake?--probably both.

PMID- 10901447
TI  - Gamma camera-mounted anatomical X-ray tomography: technology, system
      characteristics and first images.
AB  - Scintigraphic diagnosis, based on functional image interpretation, becomes more
      accurate and meaningful when supported by corresponding anatomical data. In order
      to produce anatomical images that are inherently registered with images of
      emission computerised tomography acquired with a gamma camera, an X-ray
      transmission system was mounted on the slip-ring gantry of a GEMS Millennium VG
      gamma camera. The X-ray imaging system is composed of an X-ray tube and a set of
      detectors located on opposite sides of the gantry rotor that moves around the
      patient along with the nuclear detectors. A cross-sectional anatomical
      transmission map is acquired as the system rotates around the patient in a manner
      similar to a third-generation computerised tomography (CT) system. Following
      transmission, single-photon emission tomography (SPET) or positron emission
      tomography (PET) coincidence detection images are acquired and the resultant
      emission images are thus inherently registered to the anatomical maps.
      Attenuation correction of the emission images is performed with the same
      anatomical maps to generate transmission maps. Phantom experiments of system
      performance and examples of first SPET and coincidence detection patient images
      are presented. Despite limitations of the system when compared with a state of
      the art CT scanner, the transmission anatomical maps allow for precise anatomical
      localisation and for attenuation correction of the emission images.

PMID- 10901448
TI  - Detection of somatostatin receptor-positive tumours using the new 99mTc-tricine
      HYNIC-D-Phe1-Tyr3-octreotide: first results in patients and comparison with 111In
      DTPA-D-Phe1-octreotide.
AB  - Indium- 111 labelled DTPA-D-Phe1-octreotide (DTPA-OC, OctreoScan) has been
      introduced into clinical routine for the detection of somatostatin receptor
      (SSTR)-positive tumours, which are predominantly of neuroendocrine origin.
      Potential further applications in other SSTR-positive cancers (e.g. small cell
      lung cancer, breast cancer, melanoma) have been limited mainly by the restricted
      availability and the high radionuclide costs. Previous attempts to introduce
      technetium-99m labelled analogues of octreotide have not been very successful in
      terms of the labelling procedure, in vivo biodistribution and/or tumour detection
      capabilities. The aim of this study was to assess the performance of the new
      99mTc-labelled analogue HYNIC-D-Phe1-Tyr3-octreotide (HYNIC-TOC), using tricine
      as co-ligand, for the detection of SSTR-positive tumours in patients in
      comparison with 111In-DTPA-OC. Overall, 13 patients were examined using 99mTc
      tricine-HYNIC-TOC. Twelve patients had proven SSTR-positive tumours, while one
      patient presented with an SSTR-negative tumour. In 9 of the 13 patients both
      tracers (99mTc-tricine-HYNIC-TOC and 111In-DTPA-OC) were used. Serial whole-body
      scans, spot views and/or single-photon emission tomography studies were
      performed. Images were qualitatively and semi-quantitatively (ROI analyses)
      evaluated. The biodistribution of 99mTc-tricine-HYNIC-TOC in patients showed high
      physiological uptake in kidneys, moderate uptake in liver and spleen and little
      uptake in the gut. The tracer showed predominantly renal and negligible
      hepatobiliary excretion. Known SSTR-positive tumour sites showed rapid and
      intense tracer accumulation. 99mTc-tricine-HYNIC-TOC demonstrated rapid tissue
      uptake within the first hour after injection and had basically no significant
      clearance (<20%) from normal or tumour tissue thereafter. In contrast, 111In-DTPA
      OC showed continuous clearance from normal tissues as well as renal and very
      little hepatobiliary excretion. Nevertheless, the patterns of accumulation of
      99mTc-tricine-HYNIC-TOC in tumours and normal organs were comparable to those of
      111In-DTPA-OC. A lesion-by-lesion comparison showed comparable tumour detection
      capabilities in intrahepatic tumour sites and superior capabilities of 99mTc
      tricine-HYNIC-TOC in respect of extrahepatic lesions. In conclusion, 99mTc
      tricine-HYNIC-TOC shows promise as a tracer for SSTR imaging, given its
      favourable clinical characteristics (specific and high receptor affinity, good
      biodistribution, renal excretion, low radiation exposure, high imaging quality,
      on-demand availability) and cost-effectiveness. 99mTc-tricine-HYNIC-TOC allows
      earlier diagnosis (10 min-4 h) compared with 111In-DTPA-OC (4-24 h).

PMID- 10901449
TI  - Copper bis(diphosphine) complexes: radiopharmaceuticals for the detection of
      multi-drug resistance in tumours by PET.
AB  - Experience with imaging of the multi-drug resistance (MDR) phenotype in tumours
      using technetium-99m sestamibi, a substrate of the P-glycoprotein (Pgp)
      transporter, suggests that better quantification of images and separation of MDR
      from other variables affecting tracer uptake in tumours are required. One
      approach to these problems is the development of short half-life positron
      emitting tracers which are substrates of Pgp. Several lipophilic cationic
      copper(I) bis(diphosphine) complexes labelled with copper-64 have been
      synthesised and evaluated in vitro as substrates for Pgp. The synthesis is rapid
      and efficient with no need for purification steps. The chemistry is suitable for
      use with very short half-life radionuclides such as copper-62 (9.7 min) and
      copper-60 (23.7 min). Incubation of the complexes with human serum in vitro
      showed that they are sufficiently stable in serum to support clinical imaging,
      and the more lipophilic members of the series are taken up rapidly by cells
      (Chinese hamster ovary and human ovarian carcinoma) in vitro with great avidity.
      Uptake in human ovarian carcinoma cells is significantly reduced after several
      months of conditioning in the presence of doxorubicin, which induces increased
      Pgp expression. Uptake in hooded rat sarcoma (HSN) cells, which express Pgp, is
      significantly increased in the presence of the MDR modulator cyclosporin A.
      Biodistribution studies in hooded rats show rapid blood clearance, excretion
      through both kidneys and liver, and low uptake in other tissues. The one complex
      investigated in HSN tumour-bearing rats showed uptake in tumour increasing up to
      30 min p.i. while it was decreasing in other tissues. We conclude that
      diphosphine ligands offer a good basis for development of radiopharmaceuticals
      containing copper radionuclides, and that this series of complexes should undergo
      further evaluation in vivo as positron emission tomography imaging agents for
      MDR.

PMID- 10901450
TI  - Nationwide standardisation and evaluation of scintigraphic gastric emptying:
      reference values and comparisons between subgroups in a multicentre trial.
AB  - By means of a standardised procedure, reference values for scintigraphic gastric
      emptying were established. The influence of gender, age, menstrual cycle, body
      mass index (BMI) and smoking habits was also evaluated. Eight centres recruited
      20 healthy subjects each. The meal consisted of a technetium-99m labelled omelet
      (1,300 kJ) and of 150 ml unlabelled soft drink. Geometric means of frontal and
      dorsal acquisitions were utilised in a linear fit model for determination of the
      linear emptying rate, and by using the intercepts of the regression line with the
      90% and 50% levels, the lag phase and half-emptying time, respectively, were
      defined. All individuals showed an initial lag phase and subsequent linear
      emptying. Because of a longer lag phase and a slower linear emptying rate,
      premenopausal women had a slower gastric emptying than postmenopausal women and
      men of all ages. The gastric emptying rate increased with age in the women,
      mainly due to a shortened lag phase, while the emptying rate remained almost
      unchanged with age in the males. There were no significant differences in results
      between the centres. The menstrual cycle, BMI and smoking habits did not affect
      emptying. In conclusion, the fact that the results showed a slower gastric
      emptying rate in younger women compared with older women and men indicates that
      it is necessary to use separate reference values for fertile females.

PMID- 10901451
TI  - Pethidine-augmented white cell scintigraphy in inflammatory bowel disease.
AB  - Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) white cell
      scintigraphy is invaluable for assessing the presence and extent of disease
      activity in patients with inflammatory bowel disease. Interpretation of images
      can be compromised by physiological excretion of tracer into the bowel via the
      biliary tree. This study assesses the effect of intravenous pethidine
      administered with the labelled white cells in an attempt to reduce the
      enterohepatic circulation of the tracer. Ninety-one subjects with proven or
      suspected inflammatory bowel disease were included in this study, all of whom
      underwent 99mTc-HMPAO white cell scintigraphy. The control group of 50 subjects
      underwent the standard protocol for this study performed in our department. The
      other 41 subjects received an intravenous injection of 0.3 mg/kg of pethidine at
      the same time as re-injection of the labelled white cells. Images were graded
      using a five-point scale at both 1 and 2.5 h and categorised as positive,
      negative or non-diagnostic. Each scan was also assessed for the presence of a
      visible gall-bladder. The pethidine group had significantly fewer non-diagnostic
      scans than the control group (P=0.003), and significantly (P=0.001) more studies
      in which the gall-bladder was visualised. It is concluded that the use of
      pethidine appears to reduce biliary excretion of tracer during 99mTc-HMPAO white
      cell scintigraphy. This may allow the delayed images, and early images with low
      grade tracer uptake in the bowel, to be interpreted with greater confidence and
      thereby reduce the number of scans classified as non-diagnostic.

PMID- 10901452
TI  - Sternal wound infection revisited.
AB  - Sternal wound infections (SWIs) can be subdivided into two types, superficial or
      deep, that require different treatments. The clinical diagnosis of superficial
      SWI is normally easy to perform, whereas the involvement of deep tissues is
      frequently difficult to detect. Therefore, there is a need for an imaging study
      that permits the assessment of SWIs and is able to distinguish between
      superficial and deep SWI. The present work was a prospective study aiming to
      evaluate the role of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO)
      labelled leucocyte scan in SWI management. Twenty-eight patients with suspected
      SWIs were included in the study. On the basis of clinical examination they were
      subdivided into three groups: patients with signs of superficial SWI (group 1),
      patients with signs of superficial SWI and suspected deep infection (group 2) and
      patients with suspected deep SWI without superficial involvement (group 3). Ten
      patients previously submitted to median sternotomy, but without suspected SWI,
      were also included in the study as a control group (group 4). All patients with
      suspected SWI had bacteriological examinations of wound secretion, if present. In
      addition 99mTc-HMPAO labelled leucocyte scan was performed in all patients. The
      patients of groups 1, 2 and 3 were treated on the basis of the clinical signs and
      microbiological findings, independently of the scintigraphic results. The
      patients of group 4 did not receive treatment. The final assessment of infection
      was based on histological and microbiological findings or on long-term clinical
      follow-up. Sensitivity, specificity, accuracy and positive and negative
      predictive values for scintigraphic and non-scintigraphic results were
      calculated. In the diagnosis of superficial and deep SWI, clinical and
      microbiological examination (combined) yielded, respectively, a sensitivity of
      68.7% and 100%, a specificity of 77.3% and 80.8%, an accuracy of 73.7% and 86.8%,
      a positive predictive value of 68.7% and 70.6% and a negative predictive value of
      77.3% and 100%. The scintigraphic results obtained in superficial SWI yielded a
      sensitivity of 56.2%, a specificity of 90.9%, an accuracy of 76.3%, a positive
      predictive value of 81.8% and a negative predictive value of 74.1%, while, by
      contrast, in deep SWI all of these values were 100%. Therefore, one can conclude
      that 99mTc-HMPAO labelled leucocyte scan permits accurate diagnosis of deep SWI,
      solving the main clinical problem in this field. In the present study the
      categorisation of patients without taking into account 99mTc-HMPAO labelled
      leucocyte planar scan findings caused a non-negligible number of cases of
      superficial SWI to be treated as though they were deep SWI. This "overestimation"
      led to unnecessary surgery, increased and prolonged use of antibiotics with more
      (higher) toxicity and additional expense.

PMID- 10901453
TI  - Technetium-99m labelled macroaggregated albumin arterial catheter perfusion
      scintigraphy: prediction of gastrointestinal toxicity in hepatic arterial
      chemotherapy.
AB  - Gastrointestinal toxicity from hepatic arterial infusion (HAI) of floxuridine in
      patients with liver metastases is probably due to extrahepatic perfusion or to
      partial escape of the drug from first-pass liver extraction. The aim of this
      study was to verify the role of technetium-99m-labelled macroaggregated albumin
      (99mTc-MAA) arterial catheter perfusion scintigraphy at the beginning of each
      chemotherapy cycle in decreasing or preventing gastrointestinal toxicity. We
      studied 167 consecutive patients. On the basis of the scintigraphic follow-up and
      the presence or absence of an intrahepatic arteriovenous shunt (IHAVS), we
      classified our patients into the following groups: (1) FU+ hepatic distribution
      pattern (DP), comprising 29 patients with regular scintigraphic follow-up who
      showed the expected distribution pattern at each control or a distribution
      pattern with transient alterations (extrahepatic escape) promptly reversed by the
      replacement of the catheter. Among these 29 patients there was one case of
      gastrointestinal toxicity. (2) FU- hepatic DP, comprising 128 patients who were
      evaluated with 99mTc-MAA only at the beginning of the first chemotherapy cycle,
      showed the expected distribution pattern and underwent HAI with no further
      scintigraphic evaluation. Among these 128 patients there were 28 cases of
      gastrointestinal toxicity. (3) FU+ pulmonary DP, comprising three patients with
      abnormally elevated pulmonary uptake (higher than 5%) and with regular
      scintigraphic follow-up. There were two cases of gastrointestinal toxicity among
      these three patients. (4) FU- pulmonary DP, comprising seven patients with
      abnormally elevated pulmonary uptake and without regular scintigraphic follow-up.
      There were four cases of gastrointestinal toxicity among these seven patients.
      The incidence of toxicity was significantly higher in group FU- hepatic DP than
      in group FU+ hepatic DP (21.9% vs 3.4%, P<0.05). In both the FU+ pulmonary DP and
      FU- pulmonary DP groups, the incidence of gastrointestinal toxicity was higher
      than 50%, with no significant difference between them. We conclude that, when
      performing 99mTc-MAA perfusion scintigraphy, the presence of an abnormally
      elevated pulmonary uptake (IHAVS higher than 5%) is the most relevant positive
      prognostic index for the development of gastrointestinal toxicity. Furthermore,
      in the absence of abnormal pulmonary uptake (IHAVS lower than 5%), strict
      scintigraphic follow-up is useful since it is able to promptly diagnose the
      presence of extrahepatic abdominal perfusion and thus to prevent the occurrence
      of gastrointestinal toxicity.

PMID- 10901454
TI  - Cardiac fluorine-18 fluorodeoxyglucose imaging using a dual-head gamma camera
      with coincidence detection: a clinical pilot study.
AB  - Dual-headed gamma cameras with coincidence detection (MCD) are increasingly used
      for imaging of positron-emitting tracers, such as fluorine-18 fluorodeoxyglucose
      (FDG). In this study, we examined differences between FDG MCD and FDG positron
      emission tomography (PET) as the gold standard to determine whether FDG MCD could
      be used for assessment of myocardial viability in daily practice. Nineteen
      patients with a previous myocardial infarction (17 men; mean left ventricular
      ejection fraction 44%+/-13%) underwent FDG MCD, FDG PET, resting echocardiography
      and technetium-99m tetrofosmin gated single-photon emission tomography (SPET). At
      the 50% threshold value for FDG PET, the area under the receiver operating
      characteristic curve for FDG MCD was 0.77+/-0.03. In 107 dyssynergic segments on
      echocardiography and 151 segments with hypoperfusion on 99mTc-tetrofosmin SPET,
      the specificity of FDG MCD for the detection of myocardial viability was 72% and
      76% respectively, with a sensitivity of 69% and 72% respectively. Regional
      analysis showed a significantly lower agreement of FDG MCD and FDG PET in the
      inferior and septal regions (58% for dyssynergic segments and 65% for segments
      with hypoperfusion), as compared with the other regions (85% for dyssynergic
      regions, P<0.05, and 86% for segments with hypoperfusion, P<0.05). Five patients
      (26%), who all had a body mass index > or =25% kg/m2, showed more than 25%
      disagreement between FDG MCD and FDG PET. Because of the moderate overall
      agreement with FDG PET, the low sensitivity in akinetic or dyskinetic regions and
      the low agreement in the inferior and septal regions, further studies and
      implementations of technical developments are needed before FDG MCD can be
      introduced into clinical practice for the assessment of myocardial viability.

PMID- 10901455
TI  - Evaluation of cardiac adrenergic neuronal damage in rats with doxorubicin-induced
      cardiomyopathy using iodine-131 MIBG autoradiography and PGP 9.5
      immunohistochemistry.
AB  - Doxorubicin is one of the most useful anticancer agents, but its repeated
      administration can induce irreversible cardiomyopathy as a major complication.
      The purpose of this study was to investigate doxorubicin toxicity on cardiac
      sympathetic neurons using iodine-131-metaiodobenzylguanidine (MIBG) and protein
      gene product (PGP) 9.5 immunohistochemistry, which is a marker of cardiac
      innervation. Wistar rats were treated with doxorubicin (2 mg/kg, i.v.) once a
      week for 4 (n=5), 6 (n=6) or 8 (n=7) weeks consecutively. Left ventricular
      ejection fraction (LVEF), calculated by M-mode echocardiography, was used as an
      indicator of cardiac function. Plasma noradrenaline (NA) concentration was
      measured by high-performance liquid chromatography (HPLC). 131I-MIBG uptake of
      the left ventricular wall (24 ROIs) was measured by autoradiography. 131I-MIBG
      uptake pattern was compared with histopathological results, the neuronal
      population on PGP 9.5 immunohistochemistry and the degree of myocyte damage
      assessed using a visual scoring system on haematoxylin and eosin and Masson's
      trichrome staining. LVEF was significantly decreased in the 8-week group
      (P<0.05). The serum NA level also showed no statistical difference until 4 weeks
      and was significantly increased in the 8-week group (P<0.05). MIBG uptake was
      decreased in the 6- and 8-week groups (P<0.05), and was closely correlated with
      the reduction in the number of nerve fibres on PGP 9.5 stain. Myocyte damage was
      seen only in the 8-week group. Neuronal population and the 131I-MIBG uptake ratio
      of subepicardium to subendocardium were significantly increased (P<0.05) in the 8
      week group as compared with the control group. It may be concluded that
      radioiodinated MIBG is a reliable marker for the detection of cardiac adrenergic
      neuronal damage in doxorubicin-induced cardiomyopathy; it detects such damage
      earlier than do other clinical parameters and in this study showed a good
      correlation with the reduction in the neuronal population on PGP 9.5 stain. The
      subendocardial layer appeared to be more vulnerable to doxorubicin than the
      subepicardium.

PMID- 10901456
TI  - Effect of temporal sampling on evaluation of left ventricular ejection fraction
      by means of thallium-201 gated SPET: comparison of 16- and 8-interval gating,
      with reference to equilibrium radionuclide angiography.
AB  - Gated myocardial single-photon emission tomography (SPET) allows the evaluation
      of left ventricular ejection fraction (LVEF), but temporal undersampling may lead
      to systolic truncation and ejection fraction underestimation. The aim of this
      study was to evaluate the impact of temporal sampling on thallium gated SPET LVEF
      measurements. Fifty-five consecutive patients (46 men, mean age 62+/-12 years)
      with a history of myocardial infarction (anterior 31, inferior 24) were studied.
      All patients underwent equilibrium radionuclide angiography (ERNA) and gated SPET
      4 h after a rest injection of 185 MBq (5 mCi) of thallium-201 using either 8
      interval (group 1, n=25) or 16-interval gating (group 2, n=30). In group 2, gated
      SPET acquisitions were automatically resampled to an 8-interval data set.
      Projection data were reconstructed using filtered back-projection (Butterworth
      filter, order 5, cut-off 0.20). LVEF was then calculated using commercially
      available software (QGS). A higher correlation between gated SPET and ERNA was
      obtained with 16-interval gating (r=0.94) compared with the resampled data set
      (r=0.84) and 8-interval gating (r=0.71). Bland-Altman plots showed a dramatic
      improvement in the agreement between gated SPET and ERNA with 16-interval gating
      (mean difference: -0.10%+/-5%). Using multiple ANOVA, temporal sampling was the
      only parameter to influence the difference between the two methods. When using 8
      interval gating, gated SPET LVEF was overestimated in women and underestimated in
      men (ERNA minus gated SPET = -4.0%+/-9.6% in women and 3.6%+/-7.6% in men,
      P=0.01). In conclusion, 16-interval thallium gated SPET offered the best
      correlation and agreement with ERNA, and should be preferred to 8-interval gated
      acquisition for LVEF measurement.

PMID- 10901457
TI  - Use of technetium-99m hexamethylpropylene amine oxime SPET for the study of
      cerebral blood flow reactivity after acetazolamide infusion in patients with
      Behcet's disease.
AB  - The purpose of this study was to characterise the nature of the baseline
      perfusion defects found in patients with Behcet's disease using
      hexamethylpropylene amine oxime single-photon emission tomography in conjunction
      with acetazolamide test (Acz SPET). Eleven patients underwent both baseline and
      Acz SPET. Regions of interest (ROIs) were drawn on the areas with decreased
      perfusion (D-ROI) and, in the same section, on areas with normal perfusion (N
      ROI). The ROIs were then repositioned on the corresponding section on Acz SPET.
      The mean ROI counts were then transformed into a perfusion index value (PIV) with
      reference to the global brain counts. In total we found 24 D-ROIs (17 in the
      cortical and 7 in subcortical grey matter). The influence of Acz infusion was
      selectively registered in the D-ROIs, where PIVs changed from 1.23+/-0.17
      (baseline SPET) to 1.63+/-0.23 (Acz SPET) (P<0.001). No significant difference
      was seen in the N-ROIs (1.46+/-0.21 and 1.40+/-0.17, respectively, on baseline
      SPET and Acz SPET). Our results demonstrate that Acz infusion increases the
      regional cerebral blood flow within baseline grey matter perfusion defects. This
      finding suggests that baseline perfusion abnormalities could reflect a
      disconnection rather than local vasculitic involvement.

PMID- 10901459
TI  - Correlation of technetium-99m MIBI and thallium-201 retention in solitary cold
      thyroid nodules with postoperative histopathology.
AB  - A comparative prospective study of technetium-99m methoxyisobutylisonitrile
      (MIBI) and thallium-201 with early (15 min) and delayed (90 min for MIBI, 3 h for
      201Tl) imaging in the differentiation of thyroid lesions is presented. Forty
      patients with cold thyroid nodules visualised on 99mTc-pertechnetate scan and
      with dyskaryotic or atypical epithelial cells verified by fine needle aspiration
      biopsy underwent MIBI and 201Tl scintigraphy at 3-day intervals. Subsequent
      thyroidectomies were carried out in all patients. Semiquantitative analysis was
      performed using a lesion to non-lesion ratio on early (ER) and delayed images
      (DR). Additionally, a retention index (RI) was calculated using the formula
      RI=(DR-ER) x 100/ER. The reproducibility of the method for the early and delayed
      measurements was tested by analysing intra- and inter-observer variability and
      repeatability coefficients. Histopathologically, the nodules were found to be
      well-differentiated thyroid cancer in 21 patients and benign in 19 patients.
      There was no significant difference in the ER between malignant and benign
      lesions for either 201Tl or MIBI (P>0.05). However, for both agents significant
      differences were found between malignant and benign lesions with regard to DR
      (P<0.01 for 201Tl and P<0.001 for MIBI) and RI (P<0.001 for both agents).
      Statistical comparison of the two agents showed no significant differences
      (P>0.05) except with regard to DR and RI in malignant nodules (P<0.05). A
      receiver operating characteristic analysis was performed to determine threshold
      levels for the differentiation of malignant from benign nodules. Following this
      analysis, ER, DR and RI levels of 1.03, 1.54 and 2 for MIBI and < or =1.42, 1.24
      and 5 for 201Tl were selected. Using these threshold levels, the sensitivity,
      specificity and accuracy of the study were 90.5%, 36.8% and 65% for ER MIBI,
      61.9%, 94.7% and 77.5% for DR MIBI, 95.2%, 89.4% and 92.5% for RI MIBI, 85.7%,
      47.3% and 67.5% for ER 201Tl, 80.9%, 73.6% and 77.5% for DR 201Tl, and 90.5%,
      94.7% and 92.5% for RI 201Tl. In conclusion, the DR for MIBI and 201Tl is
      superior to the ER in detecting malignant nodules, and the RI for both MIBI and
      201Tl is more valuable than the DR in differentiating malignant from benign
      thyroid nodules.

PMID- 10901458
TI  - Comparison of clinical data sets acquired on different tomographs using 6-18F-L
      dopa.
AB  - Longitudinal positron emission tomography (PET) studies of 6-18F-L-dopa uptake in
      the striatum are used to assess the progression of Parkinson's disease or the
      survival of neuronal cells grafted in parkinsonian patients. These studies are
      performed over several years, and data analysis may suffer from the change from
      old tomographs to new machines with better sensitivity and spatial resolution.
      Furthermore, such studies on parkinsonian patients may be accomplished in either
      2D or 3D acquisition mode. The aforementioned improvements offer great benefits
      for the study of neurodegenerative diseases, especially those affecting the
      striatum. However, direct comparison of data is not straightforward owing to
      variation in scanner characteristics. In this study, we assessed the feasibility
      of comparing the 6-18F-L-dopa striatal uptake values (Kc) measured in two groups
      of healthy subjects using two tomographs of different generations. We re-studied
      and compared acquisitions performed on 14 healthy subjects using 6-18F-L-dopa.
      Half of these studies had been performed in 2D acquisition mode using an ECAT
      953B. The other half had been performed in 3D acquisition mode using an ECAT
      EXACT HR+. Different reconstruction protocols were used and the Kc values
      obtained were statistically compared. The results showed that lowering the
      transverse spatial resolution of images obtained with the scanner having the
      better spatial resolution, so that it more closely matched that of the other
      machine, allowed similar KC values to be obtained in healthy subjects. This study
      shows that quantitative results of 6-18F-L-dopa scans can be matched between
      different scanners with different intrinsic resolutions. This can be accomplished
      using adequate modifications of the reconstruction parameters. Such modifications
      can be used to help in the longitudinal monitoring of parkinsonian patients using
      different tomographs.

PMID- 10901460
TI  - Benign versus malignant osseous lesions in the lumbar vertebrae: differentiation
      by means of bone SPET.
AB  - Bone scanning is a well-accepted and frequently performed diagnostic procedure
      with a high sensitivity, especially when single-photon emission tomography (SPET)
      acquisitions are added. However, the differentiation of benign from malignant
      osseous lesions often poses difficulty. The purpose of this study was to find out
      whether the particular localisation of an intraosseous lesion in a lumbar
      vertebra is an indicator of its aetiology. Bone scintigraphy including planar
      whole-body scans as well as SPET imaging of the lumbar spine was performed in 109
      patients. The diagnoses of osseous lesions in the lumbar vertebrae were made
      strictly on the basis of the findings of magnetic resonance imaging, computed
      tomography or plain radiography. Sixteen patients had to be excluded from the
      study because they did not undergo adequate radiological examination. To
      determine the particular localisation of vertebral lesions in the bone scan, two
      experienced nuclear medicine physicians examined the studies independently while
      blinded to the radiological results. Four anatomical regions were differentiated
      within the vertebra: the vertebral body, the pedicle, the facet joints and the
      spinous process. Clopper-Pearson analysis, which takes into account the number of
      examinations, yielded the following probability intervals for the malignancy of
      intraosseous lesions in the lumbar spine: vertebral body 36.8%-57.3%, pedicle
      87.7%-100%, facet joints 0.8%-21.4% and spinous process 18.7%-81.3%. It was
      concluded that lesions affecting the pedicle are a strong indicator for
      malignancy, whereas involvement of the facet joints is usually related to benign
      disease. Lesions affecting the vertebral body or the spinous process do not show
      a clear tendency towards either malignancy or benignity. In contrast to other
      studies, a significant probability of malignancy (35.6%) was observed in lesions
      affecting exclusively the vertebral body.

PMID- 10901461
TI  - Can dimercaptosuccinic acid renal scintigraphy be used to assess global renal
      function?
AB  - Use of dimercaptosuccinic acid (DMSA) has been proposed for the assessment of
      both relative and absolute renal function. Our aim was to test whether the renal
      absolute DMSA uptake (ADU) can reflect the absolute renal function from a
      theoretical point of view. A simple model was used to compute the ADU in the case
      of injury to one kidney. It was found that the assumption that ADU correctly
      reflects the absolute renal function may lead to a more than 50% overestimation
      of the function of both the normal and the impaired kidney. The later the
      measurement is made and the more impaired is the kidney, the more important is
      the error. Although DMSA can reliably quantify the relative renal function, it
      should not be used to assess absolute renal function lest major overestimation
      should occur.

PMID- 10901462
TI  - Monitoring response to therapy in cancer using [18F]-2-fluoro-2-deoxy-D-glucose
      and positron emission tomography: an overview of different analytical methods.
AB  - [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is
      considered a valuable tool in the diagnosis and staging of cancer. In addition,
      it seems promising as a technique to monitor response to therapy. Progress is
      hampered, however, by the fact that various methods for the analysis of uptake of
      FDG in tumours have been described and that it is by no means clear whether these
      methods have the same sensitivity for monitoring response to treatment. As
      interest in monitoring response using FDG PET is growing, the danger exists that
      non-optimal methods will be used for evaluation. Hence an overview of the various
      analytical methods is given, highlighting both advantages and shortcomings of
      each of the methods. The ideal analytical method for response monitoring should
      represent an optimal trade-off between accuracy and simplicity (clinical
      applicability). At present, that trade-off still needs to be defined. Studies
      relating response, as measured with any of the available analytical methods, to
      outcome are urgently needed. Until then response monitoring studies should be
      conducted in such a way that all analytical methods can be compared with the most
      quantitative one, which at present is full compartmental modelling of the data.

PMID- 10901463
TI  - Optimisation of 99mTc-Nanocoll sentinel node localisation in carcinoma of the
      breast.

PMID- 10901464
TI  - Detection of lymph node metastases by lymphoscintigraphy with a tumour-seeking
      tracer in breast cancer patients.

PMID- 10901465
TI  - Are intraoperative gamma probes imaging devices?

PMID- 10901466
TI  - Quantitation in planar renal scintigraphy: which mu value should be used?

PMID- 10901467
TI  - Quantitative assessment of regional myocardial blood flow using oxygen-15
      labelled water and PET: a multicentre evaluation in Japan.

PMID- 10901468
TI  - Development of the standard reference plane for the Heidelberg retina tomograph.
AB  - BACKGROUND: Topometry of the optic disc is the quantitative assessment of the
      structure of the optic nerve head by means of three-dimensional parameters. The
      parameter values depend on definitions of intraocular reference planes. PURPOSE:
      To describe the development of intraocular reference planes in laser scanning
      tomography for the Heidelberg Retina Tomograph (HRT) using image intrinsic data
      with a fixed offset reference plane (320 microm) and to present a contour-line
      based "flexible" standard reference plane ("SRP") for calculation of
      intrapapillary stereometric parameters taking the interindividual variability of
      optic disc topography into account. METHODS: Ten-degree triple images were
      obtained by laser scanning tomography from 99 glaucoma eyes and 180 normal eyes.
      The images were evaluated to assess the variability of height measurements of an
      optic disc border contour-line segment (6 degrees width) corresponding to the
      site of the papillo-macular bundle as indicated by the average optic disc surface
      inclination angle. RESULTS: The average optic disc surface inclination angle was 
      7 degrees +/- 3 degrees below the horizontal meridian (0 degrees). The 6 degrees
      wide contour-line segment for the SRP was chosen according to the average surface
      inclination angle (-10 degrees to -4 degrees). The reproducibility of the SRP
      segment height measurements was 16.0+/-10.8 microm for normal eyes and 23.4+/
      18.0 microm for glaucoma eyes. To ensure that the automatic reference level
      determination for intrapapillary parameters remained below the disc border
      height, we defined the SRP level at a 50 microm offset (>2 SD of average segment
      height reproducibility in glaucoma) added to the individual height position of
      the 6 degrees contour line segment. CONCLUSION: The flexible standard reference
      plane allows for automatic determination of intrapapillary variables once a disc
      border contour line is interactively defined. In contrast to a fixed offset
      reference plane (e.g. 320 microm below the mean retina height), the
      interindividual variability of optic disc topography (oblique insertion,
      glaucomatous surface flattening) is respected at the cost of the need for an
      accurate optic disc border outline.

PMID- 10901469
TI  - Resolution-improved dual-beam and standard optical coherence tomography: a
      comparison.
AB  - BACKGROUND: The purpose of the study was to demonstrate the improved axial
      resolution and longitudinal stability of dual-beam optical coherence tomography
      (OCT) in comparison to conventional OCT setups used in commercially available OCT
      instruments. METHODS: The conventional OCT technique is based on an
      interferometric setup that is rather sensitive to axial eye motions. We have
      developed a special dual-beam OCT technique which eliminates the influence of
      axial eye motions. This is achieved by using the anterior corneal surface as the
      reference surface for the interferometric ranging. To improve the signal quality,
      the different wavefront curvatures of beams reflected at cornea and retina are
      matched by a diffractive optical element. To improve the axial resolution, a
      broadband synthesized light source with an effective bandwidth of 50 nm is used,
      and the group dispersion of the ocular media is compensated. Tomographic images
      were recorded in the fovea and the optic nerve head of healthy volunteers. For
      comparison purposes, approximately the same locations in the same eyes were
      imaged by a commercially available OCT instrument. RESULTS: Compared to the
      standard OCT technique, the dual-beam OCT images show considerably improved axial
      resolution. Especially in tomograms recorded at the fovea, dual-beam OCT resolves
      microstructural details that are not visible in the standard OCT images.
      Furthermore, the axial stability of dual-beam OCT enables the recording of exact
      geometrical contours of fundus layers. CONCLUSIONS: Dual-beam OCT is able to
      provide structural information on the ocular fundus that is not obtained with
      standard OCT. The long recording times of our instrument limit the transverse
      resolution to 100-150 microm at present.

PMID- 10901470
TI  - MRI measurements of normal extraocular muscles and other orbital structures.
AB  - BACKGROUND: Studies of extraocular muscle (EOM) by magnetic resonance imaging
      (MRI) need to be extended to normal subjects of different ages to obtain data on
      the muscle thickness, cross-sectional area, and the volume of EOM and other
      orbital tissues. METHODS: Forty-two orbits of 21 normal subjects in three age
      groups with an age range of 19-70 years were examined with surface-coil MRI. The
      transverse and sagittal images were used to measure the thickness of the four
      rectus muscles during fixation in different gaze positions. The coronal images
      with eyes in the primary position were used to calculate the cross-sectional
      areas. The volumes of all six EOM, orbital fatty tissue, the optic nerve and the
      eyeball were measured in the coronal plane and in either the transverse or the
      sagittal plane. RESULTS: The horizontal muscles were thinner than vertical
      muscles. Muscle volume was larger in SR (superior rectus) than in IR (inferior
      rectus), larger in SO (superior oblique) than in IO (inferior oblique), and the
      same in LR (lateral rectus) as in MR (medial rectus). No significant differences
      were found in the values of the cross-sectional area in any image plane between
      the three age groups. There were no significant differences in muscle thickness
      and size and fatty tissue volume between age groups. The muscle thickness was
      linearly correlated to the angle of the eye deviation for all four rectus
      muscles, both in the "on" and "off" directions of the muscles. CONCLUSIONS: The
      study provides quantitative data, in normal subjects of different ages, on the
      thickness and size of EOM and the volume of other orbital tissues by MRI, to
      serve as a basis for further studies on the morphological changes of EOM in
      various orbital diseases.

PMID- 10901471
TI  - Variability of dissection depth in deep sclerectomy: morphological analysis of
      the deep scleral flap.
AB  - BACKGROUND: Deep sclerectomy and similar procedures including a deroofing of
      Schlemm's canal are meeting with increasing interest owing to the limited risk
      profile of non-perforating glaucoma surgery. The aim of our study was to
      investigate how often the outer wall of Schlemm's canal or parts of the
      trabecular meshwork were incorporated in the excised tissue on deep scleral flap
      dissection by an experienced glaucoma surgeon. METHODS: The excised deep scleral
      flap was prepared for light microscopy after performing deep sclerectomy in 7
      children and 22 adult patients suffering from glaucoma. Meridional serial
      sections were checked for the presence of fragments of trabecular beams and
      collector channels and parts of the endothelial wall of Schlemm's canal.
      Morphology was compared with the intraoperative appearance of the operated
      tissue. RESULTS: In 15 patients (52%) the deep scleral flap contained at least
      some tissue from the outer wall of Schlemm's canal; in 5 of these 15 patients
      noticeable remnants of the juxtacanalicular trabecular meshwork were also found,
      although only in one patient was this obvious during surgery. In 14 patients
      (48%) no evidence of the deroofing of Schlemm's canal was found within the
      excised deep scleral flap, although intraoperatively the dissection seemed to
      have been too superficial in only 5 patients. CONCLUSION: Even when performed by
      an experienced glaucoma surgeon, deep sclerectomy produces biopsy material of
      remarkable morphological variability that does not always correspond to the
      intraoperative appearance of the site of operation. More than in conventional
      trabeculectomy this variability may be of importance for the outcome of surgery.

PMID- 10901472
TI  - Quantitative measurements of changes of idiopathic stage 3 macular holes after
      vitrectomy using confocal scanning laser tomography.
AB  - PURPOSE: To perform quantitative three-dimensional analysis of changes of
      idiopathic full-thickness stage 3 macular holes following vitrectomy and gas
      tamponade using confocal scanning laser tomography to study the mechanism of
      repairing the holes and to correlate with visual recovery. METHODS: We studied 44
      patients, 10 men and 34 women, aged between 40 and 76 years (mean 65.5 years)
      with stage 3 macular holes with symptoms of 1-4 months' duration (mean 2.7
      months). Using the Heidelberg Retina Tomograph, we measured the macular area
      within 1 week before surgery (3.5+/-1.6 days), and between 2 and 4 weeks (2.4+/
      0.6 weeks) and at least 3 months (3.8+/-00.8 months) after surgery. RESULTS: All
      44 eyes showed closure of the holes and flattening of cuff and retinal striae
      after vitrectomy and gas tamponade. All the eyes showed small flat depressions
      that corresponded to each macular hole with the area of 0.027-0.184 mm2 (0. 110+/
      0.042 mm2). Thirty-nine (89%) of 44 eyes showed large concave depressions that
      appeared to correspond to the preoperative retinal striae, with areas of 0.844 to
      5.563 mm2 (3.688+/-1.263 mm2). The areas of the postoperative small depressions
      and large depressions were significantly correlated with the area, volume, and
      depth of the macular holes and the area of the cuff and retinal striae prior to
      treatment. Postoperative visual acuity showed significant correlations with the
      areas of the postoperative small depressions and large depressions. CONCLUSIONS:
      Confocal scanning laser tomography is potentially useful as a noninvasive
      diagnostic technique for quantitative measurements of changes of macular holes by
      vitrectomy and gas tamponade. Postoperative small depressions corresponding to
      the healed macular holes appeared to be caused by gliosis involving sealing of
      the holes. The large depressions and their concave shape may result from
      postoperative changes of the retina, including swelling of ganglion cells and
      loss of outer and inner segments of photoreceptor cells in regions of
      preoperative cuff and retinal striae.

PMID- 10901473
TI  - Open globe injuries in children.
AB  - BACKGROUND: Eye injuries are the leading cause of monocular blindness in
      children. At present, however, only limited follow-up studies exist. METHODS: The
      files of 38 consecutive patients aged 16 years or younger who had been treated
      for open globe injuries were examined. The type of injury was classified and the
      severity of injury was categorized in four grades. RESULTS: Our series included 5
      eyes (13%) with a rupture, 30 (79%) with a penetrating and 3 (8%) with a
      perforating injury. Follow-up varied from 3 days to 7 years (mean 15.5 months).
      The macula was attached at the last follow-up in all eyes. The final visual
      acuity ranged between 1.0 and light projection. In 47% of cases (18 eyes), the
      visual acuity was > or =0.5; 74% (28 eyes) achieved at least 0. 1. Eighteen of 38
      eyes (47%) had severe injury with posterior segment involvement. Visual acuity of
      at least 0.5 was achieved in 44% (8/18) of these. Eyes with grade 2-4 injury
      treated with early vitrectomy had a final visual acuity of > or =0.5 in 58% of
      cases (7/13). Twenty-one (55%) of 38 children were < or =8 years of age and eight
      of them (38%) had a final visual acuity of > or =0.5. CONCLUSION: Salvage of the
      eye with an attached macula was possible in all eyes. Even in severely injured
      eyes good visual acuity can be established in about 50% of cases.

PMID- 10901474
TI  - The full-field temporal contrast sensitivity test for glaucoma: influence of
      cataract.
AB  - PURPOSE: To determine the influence of lens opacities on temporal contrast
      sensitivity, measured by the full-field flicker test ("Erlangen flicker test").
      METHODS: Thirty-six consecutive patients (mean age 71.1+/-11.6 years, 12 male, 24
      female, refractive error -1.5+/-3.8 dpt) with cataract (visual acuity 0.21+/
      0.16, retinal acuity 0.56+/-0.32, no glaucoma) were studied. Temporal contrast
      sensitivity (full-field flicker test, 37.1 Hz) and lens opacity (back scatter
      Lens Opacity Meter, Interzeag) were measured preoperatively and on the 3rd
      postoperative day. STATISTICS: nonparametric tests (Wilcoxon-test, Spearman
      correlation coefficient, Mann-Whitney U-test). RESULTS: No significant difference
      was seen in temporal contrast sensitivity pre- and postoperatively, but there was
      a significant difference in lens opacity measurements pre- and postoperatively.
      No significant correlation was found between temporal contrast sensitivity and
      lens opacity values preoperatively and postoperatively. CONCLUSION: The temporal
      contrast sensitivity, measured by the full-field flicker test, seems to be
      independent of lens opacity due to the range of cataract included in this study.
      The data indicate that the full-field flicker test is useful for early glaucoma
      detection even in patients with cataract formations.

PMID- 10901475
TI  - The additive intraocular pressure-lowering effect of latanoprost 0.005% daily
      once and pilocarpine 2% t.i.d. in patients with open-angle glaucoma or ocular
      hypertension. a 6-month, randomized, multicenter study. German Latanoprost Study
      Group.
AB  - PURPOSE: To compare the additional intraocular pressure-lowering effect of
      latanoprost 0.005% administered once daily with that of pilocarpine 2%
      administered three times daily in patients with primary open-angle glaucoma or
      ocular hypertension currently on monotherapy with timolol 0.5% twice daily.
      METHODS: In a 6-month, multicenter, randomized, open-label study 242 patients
      with POAG or OH whose IOP was not controlled with timolol 0.5% b.i.d. were
      enrolled. Eyes had not been treated with pilocarpine and latanoprost for at least
      2 years. An analysis of covariance with diurnal IOP change from baseline to month
      6 for study eyes was performed. RESULTS: Four patients on latanoprost 0.005% and
      35 on pilocarpine 2% did not complete the study (P<0.001). Two hundred and forty
      patients were included in the intent-to-treat analysis. For both treatments the
      diurnal IOP reduction after 6 months was statistically significant (P<0.001). IOP
      (mean+/-SD) was reduced from 23.3+/-2.8 to 17.8+/-2.8 (-5.6) mmHg in the
      latanoprost 0.005% group and from 23.0+/-3.2 to 18.5+/-2.4 (-4.8) mmHg in
      pilocarpine 2% t.i.d.-treated eyes. The mean difference of -0.8 mmHg (per
      protocol, PP) and -1.6 mmHg (intend-to-treat, ITT) was statistically significant
      (P<0.04, PP; P<0.001, ITT) in favor of latanoprost 0.005%. Two eyes treated with
      latanoprost showed an iris color change. Thirty-six patients in the latanoprost
      group and 106 in the pilocarpine 2% group reported ocular adverse events
      (P<0.001). CONCLUSION: From the data we conclude that the additivity of
      latanoprost 0.005% is at least as effective as pilocarpine 2% t.i.d. in reducing
      IOP when added to eyes currently on monotherapy with timolol 0.5% b.i.d.
      Latanoprost was better tolerated than pilocarpine 2% eye drops in this study. The
      increase in iris pigmentation requires further investigation.

PMID- 10901476
TI  - Herbimycin A in the treatment of experimental proliferative vitreoretinopathy:
      toxicity and efficacy study.
AB  - BACKGROUND: Proliferative vitreoretinopathy (PVR) is partially caused by peptide
      growth factors, stimulating the cell by binding to a transmembrane tyrosine
      kinase receptor. We studied the effects of herbimycin A (HA), a tyrosine kinase
      inhibitor, in PVR. METHODS: Toxicity studies: Electroretinography and
      histological studies were performed after intravitreal injection of HA. Efficacy
      studies: Homologous rabbit dermal fibroblasts were injected intravitreally,
      followed by injection of HA. The presence of tractional retinal detachment (TRD)
      and severity of inflammation were assessed. RESULTS: Toxicity studies: Eyes
      injected with HA exhibited decrease in B-wave amplitude initially, with
      subsequent recovery. Histologically, damage to photoreceptors was evident after
      injection of high but not of low doses of HA. Efficacy studies: Inflammatory
      response and the development of TRD were significantly reduced with all doses of
      HA. CONCLUSIONS: HA (20 microM) was found to be effective and safe in preventing
      the development of inflammation and TRD.

PMID- 10901477
TI  - Nitric oxide production by isolated human and porcine ciliary processes.
AB  - BACKGROUND: In the kidney, the trachea, and the colon, nitric oxide (NO) can
      modulate transepithelial fluid transport. This study investigates whether
      isolated human and porcine ciliary processes produce NO. METHODS: Porcine ciliary
      processes and iris were used either fresh or thawed after storage at -70 degrees
      C. Post-mortem (8-12 h) human ciliary processes were used thawed after storage at
      -70 degrees C. NO was measured by placing a nafion-coated polymeric porphyrinic
      microsensor (differential pulse voltammetry) on the surface of the tissue.
      Measurements were conducted in the absence or in the presence of the NO formation
      inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 0.2 mM, 1 mM) or its
      biologically inactive D-enantiomer N(G)-nitro-D-arginine methyl ester (D-NAME; 1
      mM). RESULTS: NO concentrations in porcine ciliary processes (1.27+/-0.25 microM)
      were higher (P=0.001) than those in the iris (0.00+/-0.02 microM) and were
      significantly (P<0.001) decreased by L-NAME (fresh specimen). From thawed porcine
      ciliary processes, NO concentrations measured (1.85+/-0.47 microM) were not
      significantly different (P=0.16) from those measured in fresh specimen and were
      also reduced (P <0.001) by L-NAME, but not by D-NAME. In human ciliary processes,
      NO concentrations measured (0.08+/-0.11 microM) were somehow lower but were again
      decreased (P<0.001) by L-NAME (thawed specimen). CONCLUSION: Reflecting the
      biological activity of a nitric oxide synthase, isolated human and porcine
      ciliary processes produce NO.

PMID- 10901478
TI  - Octyl 2-cyanoacrylate in sutureless surgery of extraocular muscles: an
      experimental study in the rabbit model.
AB  - BACKGROUND: Sutureless surgery for strabismus eliminates the risk of perforating
      the ocular bulb in patients with extremely thin sclerae. Thus far, however, the
      results obtained with tissue adhesives such as the cyanoacrylates instead of
      sutures have been less than satisfactory. METHODS: A new adhesive, octyl 2
      cyanoacrylate, was tested in 36 rabbit eyes in which the superior rectus was
      recessed 5 mm. In 36 other eyes the same operation was performed using 5/0 Vicryl
      sutures. Animals were killed 1, 3, 5, 15, 30 and 45 days after surgery. One eye
      from each animal was used for histopathological examination of the reinserted
      muscle and sclera, while the other was used in a tensiometric test to measure how
      many grams of weight were needed to detach the muscle from its new insertion
      site. RESULTS: The tensile strength of the bond achieved with the cyanoacrylate
      adhesive was 94+/-12 g 1 day after surgery (vs 238+/-19 g in the suture group)
      and 520+/-24 g after 45 days (vs 576+/-27 g with sutures). No cases of slippage,
      muscle detachment, or local tissue reactions were observed in either group. There
      were no differences in histological findings between the eyes of the two groups.
      CONCLUSIONS: Although further study will be necessary before this technique can
      be used in humans, our findings indicate that octyl 2-cyanoacrylate is superior
      to the cyanoacrylate adhesives used in the past in terms of adhesion and holding
      power; given its favorable toxicity profile, this product may offer interesting
      applications in the future.

PMID- 10901479
TI  - Effect of topical povidone-iodine versus topical ofloxacin on experimental
      Staphylococcus keratitis.
AB  - PURPOSE: To compare the antibacterial effect of povidone-iodine (PI) with that of
      ofloxacin in an experimental model of bacterial keratitis. METHODS:
      Staphyloccocal keratitis was induced in 21 eyes of Dutch Belted rabbits by
      intrastromal inoculation of approximately 280 organisms of Staphylococcus aureus.
      Six hours later, the animals were divided in four groups treated topically with
      saline 0.9%, Betadine 10%, Betadine 0.5% or Ofloxacin 0.3% (2 gtt every 30 min
      for 8 h). The central 8-mm cornea was excised, washed and homogenized. Colony
      counts were performed on serial 10-fold dilutions plated on blood and brain
      infusion agar and incubated overnight. RESULTS: Colony-forming units per cornea
      were 7.4x10(7) for the saline group compared to 8.2x10(7) for PI 10% (P>0.5),
      4.3x10(7) for PI 0.5% (P<0.01) and no organisms for ofloxacin 0.3%. CONCLUSIONS:
      Betadine 0.5% demonstrates a statistically significant bactericidal effect
      compared with untreated staphyloccocal keratitis in our experimental model.
      Ofloxacin has superior antibacterial effect under the conditions studied. Further
      improvements in the povidone-iodine formulation are warranted prior to
      consideration for human keratitis.

PMID- 10901480
TI  - A noninvasive method of measuring wave intensity, a new hemodynamic index:
      application to the carotid artery in patients with mitral regurgitation before
      and after surgery.
AB  - Wave intensity (WI) is a new hemodynamic index, which is defined as
      (dP/dt)(dU/dt) at any site of the circulation, where dP/dt and dU/dt are the time
      derivatives of blood pressure and velocity, respectively. Arterial WI in normal
      subjects has two positive sharp peaks. The first peak occurs during early systole
      when a forward-traveling compression wave is generated by the left ventricle. The
      magnitude of this peak increases markedly with an increase in cardiac
      contractility. The second peak, which occurs towards the end of systole, is
      caused by generation of a forward-traveling expansion wave by the ability of the
      left ventricle to actively stop aortic blood flow. The interval between the R
      wave of the ECG and the first peak of WI (R-1st peak interval) and the interval
      between the first and second peaks (1st-2nd interval) are approximately equal to
      the preejection period and left ventricular ejection time, respectively. Using a
      combined Doppler and echo-tracking system, we obtained carotid arterial WI
      noninvasively. We examined the characteristics of WI in 11 patients with mitral
      regurgitation (MR) before and after surgery, and 24 normal volunteers. In the MR
      group before surgery, the second peak was decreased and the (1st-2nd interval)/(R
      R interval) ratio was reduced, compared with the normal group (140 +/- 130 vs 750
      +/- 290mmHg m/s3. P < 0.0083; 20.7% +/- 3.4% vs 26.7% +/- 2.8%, P < 0.083). There
      were no significant differences in the first peak between the normal group and
      the MR group before and after surgery. The second peak in the MR group was
      increased significantly (P < 0.016 vs before surgery) to 1,150 +/- 830mmHg m/s3
      in the early period after surgery (stage I), and to 1,090 +/- 580mmHgm/s3 in the
      late period after surgery (stage II). These values did not differ significantly
      from that of the normal group. At stage I, the (R-1st peak interval)/ (R-R
      interval) ratio was increased from 13.4% +/- 2.7% to 20.6% +/- 5.6% (P < 0.016 vs
      before surgery). At stage II, this ratio decreased to 16.2% +/- 2.8% (P < 0.016
      vs stage I). but was still significantly higher than that before surgery. The
      (1st-2nd interval)/(R-R interval) ratio increased significantly after surgery (P
      < 0.016 vs before surgery) to values (27.0% +/- 4.5% at stage I and 28.9% +/-
      2.6% at stage II) which did not differ significantly from that of the normal
      group. The recovery of the second peak after surgery suggests that the left
      ventricle had recovered the ability to actively stop aortic blood flow. Wave
      intensity is useful for analyzing changes in the working condition of the heart.

PMID- 10901481
TI  - Late complications of heart transplantation: an 11-year experience.
AB  - Advances in donor and recipient selection and postoperative management of
      patients undergoing a heart transplant have improved survival after cardiac
      transplantation; nevertheless, late complications are still the main cause of
      mortality. Between January 1988 and March 1999, 200 heart transplants and 2
      retransplants were performed at our Institution. The actuarial survival rate was
      84.45% at 1 month, 75.22% at 1 year, and 69.48% at 5 years. One-hundred forty
      five patients reached at least 6 months of follow-up. In this group of patients
      we reviewed all available pathological specimens from endomyocardial biopsies,
      autopsies, and hearts retrieved at retransplantation. The most frequent late
      complications have been: malignancies (9 patients), allograft coronary artery
      disease (ACAD) (6 patients), and infections (6 patients). All patients with ACAD
      had serological evidence of cytomegalovirus (CMV) infection and 5 of them (83.3%)
      of hepatitis C virus (HCV) infection. Squamous cell lung carcinoma and Kaposi's
      sarcoma were the most frequent neoplasms (3 patients). Twenty-six out of 145
      patients died during the follow-up: sudden death occurred in 10 patients
      (38.46%), infections caused death in 6 patients (23.08%). ACAD in 4, and cancer
      in 4. Causes and rates of late mortality in patients with a cardiac transplant
      differ from those of early mortality. Development of infections, ACAD, or cancer
      is associated with a high late mortality rate. A striking correlation has been
      found between ACAD and HCV and/or CMV positivity. suggesting that such viruses
      may play a role in the development of vascular late complications in transplanted
      hearts.

PMID- 10901482
TI  - Takayasu's arteritis and fibromuscular dysplasia as causes of acquired atypical
      coarctation of the aorta: retrospective analysis of seven cases.
AB  - Coarctation of the aorta usually occurs in the aortic isthmus: however, 2% of all
      coarctation is localized at atypical sites such as the aortic arch and the
      thoracic and/or abdominal aorta. Causal therapy involves vascular surgery, and
      during the procedure, biopsies of the involved vessels should be taken to
      establish the etiology. This study involved the retrospective analysis of
      clinical and histopathological findings for seven patients who underwent vascular
      surgical procedures (age range, 10-37 years; male/female ratio 3:4).
      Histopathological analysis of specimens revealed two pathological processes
      taking place with different localization in the aortic wall as the cause of the
      atypical coarctation of the aorta: (1) fibrosis/scarification in the tunica media
      and adventitia compatible with chronic lesions of Takayasu's arteritis (four
      cases); (2) fibromuscular dysplasia in the tunica media (three cases).

PMID- 10901483
TI  - Involvement of calcineurin in angiotensin II-induced cardiomyocyte hypertrophy
      and cardiac fibroblast hyperplasia of rats.
AB  - A rapidly emerging body of literature implicates a pivotal role for the Ca2+
      calmodulin-dependent phosphatase, calcineurin, as a cellular target for a variety
      of Ca2+-dependent signaling pathways culminating in cardiac hypertrophy. The aim
      of the present study was to test whether calcineurin is involved in the signal
      transduction of angiotensin II (AngII)-induced cardiac myocyte hypertrophy and
      fibroblast hyperplasia. Firstly, we observed that calcineurin activity was
      significantly increased in AngII-stimulated cardiac myocytes as well as
      fibroblasts, but was markedly inhibited by Losartan (50 micromol/l), H7 (50
      micromol/l), and Fura-2/AM (5 micromol/l). It is indicated that AngII-induced
      activation of calcineurin is through an ATI receptor, may be dependent on the
      sustained increases of [Ca2+]i, and be regulated by protein kinase C. In a second
      experiment, we found that cyclosporin (0.1-10micromol/l), a specific inhibitor of
      calcineurin, decreased the protein synthesis rate in AngII-stimulated
      cardiomyocytes and the DNA synthesis rate in AngII-treated fibroblasts in a dose
      dependent manner. In the latter experiment, calcineurin inhibition reduced the
      mRNA level of the atrial natriuretic factor gene. These results indicate that
      calcineurin is involved in the signal transduction of AngII-induced cardiomyocyte
      hypertrophy and fibroblast hyperplasia.

PMID- 10901484
TI  - Effects of lidocaine on isolated, blood-perfused ventricular contractility in the
      dog.
AB  - Direct inotropic effects of lidocaine on ventricular muscle were investigated in
      isolated canine left ventricular preparations which were perfused with a donor
      dog's arterial blood. Intravenous administration of lidocaine in doses of less
      than 1 mg/kg did not cause any significant hemodynamic or cardiac changes in the
      donor dog and in the isolated ventricular preparation. A large dose of 10mg/kg of
      lidocaine produced a marked depressor response in the donor and a negative
      inotropic effect in the isolated ventricle. Direct injection of lidocaine (1-30
      micromol) to the isolated preparation induced a dose-related decrease in the
      ventricular contractile force. Infusion of lidocaine (3 micromol/ml per min) did
      not influence norepinephrine- or calcium chloride-induced positive inotropic
      effects. In the frequency-force relationship, lidocaine generally depressed the
      contractility, exhibiting the positive staircase phenomenon. On the other hand, a
      calcium entry inhibitor, diltiazem, readily caused the negative staircase. From
      these results, it is concluded that (1) a large amount of lidocaine has a cardiac
      depressant property, (2) lidocaine has no antiadrenergic properties, and (3) the
      action of lidocaine may probably be due to the effect of intracellular calcium
      movement but not to a modification of Ca inward currents.

PMID- 10901485
TI  - Mode and role of cell death during progression of atherosclerotic lesions in
      hypercholesterolemic rabbits.
AB  - Two cell types, macrophages and smooth muscle cells (SMCs), play important roles
      in the development of atherosclerotic lesions. Both contribute to the formation
      of the lesions not only by their presence but also by taking in or releasing
      extracellular substrates during life and at death. The present study aimed to
      elucidate their turnover, focusing on the detailed description of the modes of
      death in each cell type, and the roles of their death in the progression from
      early into advanced atherosclerotic lesions. Ascending aortas were obtained from
      New Zealand white male rabbits fed a diet with 1% cholesterol for 3 months (3-M
      group, n= 6) and 6 months (6-M group, n = 6). They were histologically examined,
      and the cell death was checked by in situ nick end-labeling (TUNEL), using a Taq
      polymerase-based in situ ligation assay with/without combination of
      immunohistochemistry, electron microscopy (EM), and TUNEL at the EM level.
      Intimal hyperplasia and luminal stenosis advanced with increased dietary
      interval, and the aortic intima of the 3-M group consisted of histological types
      I-III atherosclerotic lesions, whereas that of the 6-M group included types III
      V. Along with the progression, the cellular population decreased, but the area of
      fibrosis increased. The percentage area of macrophages declined (from 60% +/- 5%
      to 23% +/- 2%), but that of SMCs increased (from 5% +/- 1% to 10% +/- 2%). The
      positive cells for in situ ligation were less frequent in the 6-M group (0.05% +/
      0.01%) than in the 3-M group (0.2% +/- 0.04%), which was due to a decrease in
      SMCs positive for in situ ligation. The frequency of TUNEL-positive cells was
      higher than that of in situ ligation-positive cells in both groups, suggesting
      that cell death involved not only apoptosis but also oncosis. This was confirmed
      using EM: cell death occurred via both apoptosis and oncosis. EM-TUNEL positively
      labeled not only apoptotic but also some oncotic nuclei. Death of macrophages and
      SMCs involves both apoptosis and oncosis in the aortic intima of
      hypercholesterolemic rabbits. Decline in the dying rate of SMCs might be
      associated with the formation of SMC-rich and collagen-rich lesions in the late
      advanced stage of atherosclerosis, although such a cause-effect relationship is
      to be further confirmed.

PMID- 10901486
TI  - STAND: a peer educator training curriculum for sexual risk reduction in the rural
      South. Students Together Against Negative Decisions.
AB  - BACKGROUND: The incidence of AIDS in rural areas continues to increase rapidly,
      with teenagers continuing to report high rates of sexual risk behaviors.
      Unfortunately, there is a dearth of effective HIV prevention programs targeting
      youth in rural settings where there are often formidable barriers to sex
      education programs. This paper describes a theoretically based intervention
      designed to meet the needs of rural youth. METHODS: Students Together Against
      Negative Decisions (STAND) is a 28-session teen peer educator training program
      implemented in a rural county in a southeastern state, promoting both abstinence
      and sexual risk reduction. The theoretical foundation of the curriculum includes
      both Diffusion of Innovations Theory and the Transtheoretical Model, focusing on
      both individual and community norm change. STAND is teen-centered and skills
      based; activities focus on active learning. Educator trainees are selected on the
      basis of their opinion leadership within their peer group, resulting in a
      training group of both virgin and sexually active teens, balanced for gender and
      matched to the racial proportions of the school. RESULTS: Acceptance and
      participation in STAND suggest that adolescents in rural communities can be
      accessed through community-based interventions, that they are willing to
      participate in such intensive programs, and that they perceive the intervention
      as valuable and enjoyable. Moreover, the STAND program has thrived in a
      relatively conservative rural environment, and has had a positive impact on
      adolescents' sexual risk taking. Results from a pilot study showed significantly
      greater increases in condom use self-efficacy (16% vs a 1% decrease among
      controls) and in consistent condom use (+28% vs +15%). Adolescent trainees also
      reported a sevenfold larger increase in condom use (+213% vs +31%) and a 30%
      decrease in unprotected intercourse compared to a 29% increase among controls.
      CONCLUSIONS: STAND represents a new genre of HIV prevention program, one that
      utilizes complementary theoretical models to develop a program that targets both
      individual- and community-level change for rural adolescents.

PMID- 10901487
TI  - Lead. A message from preventive medicine and your physician.

PMID- 10901488
TI  - Health risks, ability to pay, and the use of primary care: is the distribution of
      service effective and equitable?
AB  - BACKGROUND: This study clarifies the confusion about what factors are consistent
      predictors of primary care service use, of which preventive services are a major
      component. A variety of health risk, predisposing, and enabling characteristics
      were assessed for their association with the use of primary care. Variable
      selection was guided by the use of the Andersen-Newman Behavioral Model of health
      service utilization. METHODS: The responses of 1,512 residents of Oklahoma to the
      BRFS survey were used in this study. Both probit and logistic analyses were used
      to assess the use of nine preventive services and a summary index of service use.
      RESULTS: The results indicate that those at greater risk of illness and least
      able to use finance services have the lowest rates of use among the nine
      preventive services individually and when combined as an index of overall primary
      care use. CONCLUSIONS: Problems persist with the adequate distribution of primary
      care among the medically vulnerable. Furthermore, recent welfare and health
      reforms may present added obstacles to their access to quality primary care
      services. The paper concludes with a discussion of policy options that may
      improve the effectiveness of primary care and redress inequities in the use of
      these services.

PMID- 10901489
TI  - Models of the relationship of stress, depression, and other psychosocial factors
      to smoking behavior: a comparison of a cohort of students in grades 6 and 8.
AB  - BACKGROUND: Six specific hypotheses regarding putative mechanisms by which
      stressful life events might lead to initiation of smoking among adolescents were
      proposed and tested on a Grade 6 cohort of students in Scarborough, Ontario,
      Canada. In addition, the data were used to determine the set of risk factors for
      initiation of smoking most pertinent to the experience of the cohort. METHODS:
      The same relationships were examined for the 1,543 students when they were in
      Grade 8 and compared to the earlier Grade 6 results. The hypotheses include the
      effects of personal resources (coping, self-esteem, social support, and mastery),
      social conformity, rebelliousness, attitudes, smoking environment factors, and
      gender differences. RESULTS: The hypotheses were not unequivocally supported,
      except for the hypotheses about attitudes and smoking environment as well as
      gender effects. Males and females differ with regard to the variables and
      interrelationships in both years and in the final models developed. In Grade 6,
      there are more smoking environment items for males than for females. By Grade 8,
      male smoking is influenced by mastery, social conformity, and rebelliousness,
      while for females environmental smoking and rebelliousness are important.
      CONCLUSION: Male and female students differ in how stress, depression, and
      smoking are related in the presence of psychosocial factors.

PMID- 10901490
TI  - Total quality leadership in the U.S. Navy: effective for health promotion
      activities?
AB  - BACKGROUND: Although the U.S. Navy mandated Total Quality Leadership (TQL) as a
      management strategy throughout its medical department in the early 1990s, it was
      unknown to what extent it was being used for health promotion activities and, if
      so, how effectively. METHODS: A brief mail survey of 204 Navy commands
      supplemented by 97 telephone interviews to TQL-for-health-promotion-using
      commands and nonusing controls provided worksite information on TQL
      implementation. Responses from a Navywide health and fitness survey provided
      perceptions and health behavior attitudes from the individuals at commands.
      RESULTS: A total of 32% of commands surveyed had used TQL specifically for
      improving health- and fitness-related processes and outcomes between 1991 and
      1995. Participants at commands that had used TQL for health- and fitness-related
      processes reported a higher importance of good health (P < 0.05) and were more
      certain that they would reach and or maintain their ideal weight (P < 0.05) than
      participants at non-TQL commands. However, there were no significant differences
      in perceptions of command support for health and fitness between TQL and non-TQL
      commands. CONCLUSIONS: Several factors and organizational arrangements that were
      pertinent to the development and practice of TQL in the Navy were identified. The
      use of TQL specifically for health promotion was not consistently related to
      health-related perceptions or health behavior attitudes.

PMID- 10901492
TI  - Opportunities for improving inpatient smoking cessation programs: a community
      hospital experience.
AB  - BACKGROUND: This cohort study examined the role of smoking during
      hospitalization, duration of cessation counseling, patient awareness of the
      hospital's smoke-free policy, belief that smoking is associated with a current
      symptom or disease, and the presence of withdrawal symptoms with 12-month smoking
      cessation among inpatients enrolled in a smoking cessation program. METHODS:
      Inpatients in four community hospitals (N = 1,317) participated in a smoking
      cessation intervention consisting of face-to-face counseling at baseline and four
      follow-up counseling phone calls. Patients were classified as nonsmokers only if
      they reported not smoking at both the 6- and the 12-month interviews. All
      patients lost to follow-up were considered smokers. RESULTS: At 1 year the
      smoking cessation rate was 22.5%. Cessation was independently associated with
      reporting no smoking during hospitalization, noting no withdrawal symptoms at
      baseline, and believing that a current illness or symptom is related to smoking.
      Length of counseling interview and awareness of the hospital's smoke-free policy
      were not independently associated with cessation. CONCLUSIONS. Smoking cessation
      programs and hospital policies that decrease smoking during hospitalization,
      address withdrawal symptoms during hospitalization, and make clear the connection
      between a patient's health and cigarette smoking may increase the effectiveness
      of their smoking cessation efforts.

PMID- 10901491
TI  - The Hutchinson Smoking Prevention Project trial: design and baseline
      characteristics.
AB  - INTRODUCTION: This paper describes the experimental design and baseline
      characteristics of the Hutchinson Smoking Prevention Project (HSPP), a 15-year
      trial to determine to what extent a grade 3-12 school-based tobacco use
      prevention intervention can deter tobacco use throughout and beyond high school.
      DESIGN: Trial design features include use of the school district as the unit of
      randomization, inclusion of the school district's entire enrollment of 3rd
      graders, long-term follow-up of the entire original cohort, and sample size and
      evaluation methods that account for the group-randomization and intraclass
      correlation of endpoints within school districts. The theory-based intervention
      is teacher-led and includes grade 3-10 curriculum units, teacher training, grade
      9-12 tobacco use cessation materials, and high school staff newsletters. RESULTS:
      Baseline data were collected on the trial cohort of 8388 children and their
      parents and on the 40 collaborating school districts and communities. A
      comparison of the distribution of baseline variables between experimental
      conditions shows good balance. CONCLUSIONS. The HSPP trial's experimental design
      will provide a rigorous test of the intervention. The balance in baseline
      variables between the experimental and control conditions will help provide
      assurance that the trial's intervention effectiveness results, scheduled for
      publication in 2000, will be unbiased.

PMID- 10901493
TI  - The use of nicotine patches with minimal intervention.
AB  - BACKGROUND: This paper describes a natural, prospective, open-label study
      designed to evaluate the impact of free nicotine patches with minimal support for
      smoking cessation. METHODS: Surveys were administered to 223 participants who
      received nicotine patches from the American Lung Association. All participants
      received a 6-week supply of 15-mg/16-h transdermal nicotine patches, a self-help
      book Freedom from Smoking, and information about area smoking cessation classes.
      Follow-up telephone surveys were administered 6 weeks after the patches were
      distributed. Abstinence was measured through self-report exclusively. RESULTS:
      The overall quit rate at 6-weeks was 21% (47/223). Among nonquitters, the mean
      number of cigarettes smoked per day dropped from 25 at baseline to 14 at 6 weeks.
      There was a significant difference in the average number of patches used by
      quitters and nonquitters (26 versus 11, P < 0.001). CONCLUSIONS: Nicotine patches
      with minimal support can be effective in smoking cessation and smoking reduction.
      The availability of patches may have motivated participants to quit. Efforts to
      increase access to and use of nicotine patches may result in increased attempts
      to quit and successful quitting.

PMID- 10901494
TI  - Effectiveness of physician-based assessment and counseling for exercise in a
      staff model HMO.
AB  - BACKGROUND: Few primary care physicians routinely counsel for exercise, despite
      the benefits of physical activity and the high prevalence of inactivity. The
      objective of this study is to assess the effectiveness of Physician-Based
      Assessment and Counseling for Exercise (PACE), a brief, behavior-based tool for
      primary care providers counseling healthy adults. METHODS: This study is a
      randomized controlled trial of 812 patients age 30 years or older registered for
      well visits at 32 primary care physician offices at a staff model health
      maintenance organization. Intervention physicians were trained to deliver PACE
      exercise counseling protocols at the index visit, and one reminder telephone call
      occurred at 1 month. An enhanced intervention group received additional activity
      reminders. RESULTS: At the 6-month follow-up, the control group did not differ
      significantly from the intervention group for energy expended (2,048 kcal/week
      versus 2,108 kcal/ week, P = 0.77), time spent in walking or other moderate to
      vigorous activities (202 min/week versus 187 min/ week, P = 0.99), mental health,
      physical function, or behaviors previously shown to predict activity change.
      Among the intervention patients, the stages-of-change score for Contemplators
      increased significantly compared with controls (P = 0.03), but without a
      significant change in energy expended. Baseline levels of physical activity
      counseling were high (50%), as were baseline patient physical activity levels
      (61% exercised at least three times a week). CONCLUSIONS: These results suggest
      that a one-time PACE counseling session with minimal reinforcement, in a setting
      with high baseline levels of activity, does not further increase activity. The
      finding that Contemplators advanced in stage of behavior change suggests that
      further studies are needed to examine long-term, repeated counseling
      interventions.

PMID- 10901495
TI  - The microcirculation and inflammation: site of action for glucocorticoids.
AB  - The glucocorticoid hormones and their synthetic derivatives are potent
      suppressors of inflammatory and allergic pathologies. Their widespread efficacy
      is the result of multiple modes of action occurring predominantly at the level of
      the microcirculation. Indeed the glucocorticoids interfere with the function of
      all of the cellular components of the microcirculation associated with an
      inflammatory response. These agents inhibit vasodilatation of the arteriolar and
      capillary beds. therefore preventing the increase in blood flow that
      characterizes the initial stages of the inflammatory response. They also prevent
      increases in vascular permeability in the capillary and post-capillary venule,
      thereby reducing exudate formation. Finally, the glucocorticoids potently
      suppress leukocyte emigration across post-capillary venules. However, this
      promiscuity of the glucocorticoids to act at multiple sites also endows this
      class of (drugs with major side effects associated with chronic treatment. We
      propose that one way to progress forward is to understand better the effects of
      glucocorticoids within the microcirculation. This may aid identification of
      specific molecular sites of action and therefore the development of novel
      glucocorticoid molecules with fewer side effects.

PMID- 10901496
TI  - Microvascular perfusion and transport in the diabetic heart.
AB  - Diabetes is a chronic disease of metabolic dysfunction that is increasing world
      wide. The hyperglycemia associated with diabetes causes significant protein
      alterations and an oxidative stress. In the heart, all cell types are affected by
      diabetes: the myocyte, the vasculature and the blood cells. Four out of five
      diabetics die from ischemic heart disease and stroke, suggesting that the
      diabetic is quite vulnerable to ischemic injury. It is important to understand
      the pathophysiologic challenges that occur in the diabetic heart in order to
      develop thoughtful treatments to limit this serious complication. This review
      focuses on the anatomical and functional alterations that occur in the diabetic
      circulation of the heart, with emphasis on the coronary microcirculation.
      Coronary microvascular dysfunction combined with blood cellular alterations are
      presented to explain the amplified oxidative stress that occurs in the diabetic
      heart under ischemic conditions.

PMID- 10901497
TI  - The pancreas as a source of cardiovascular cell activating factors.
AB  - OBJECTIVE: Physiological shock leads to elevated levels of plasma factors that
      activate circulating leukocytes and endothelial cells, thereby compromising
      microvascular functions. The nature and source of these plasma-derived activators
      are unknown. To examine the possible origin of these factors, we homogenized rat
      internal organs and measured their activity on cardiovascular cells in vivo and
      in vitro. METHODS: Fresh tissue samples from small intestine, spleen, heart,
      liver, kidney, adrenals, and pancreas were homogenized. Their ability to induce
      leukocyte pseudopod formation and nitroblue tetrazolium (NBT) reduction was
      tested and their impact in vivo on blood pressure, survival, and microvascular
      cell injury was examined. RESULTS: A dramatic increase (p < 0.001) in leukocyte
      activation compared to controls was observed with pancreas homogenate but not
      with homogenates from the other organs. Leukocyte activation was induced by
      homogenates of other tissues only after prior incubation with substimulatory
      concentrations of pancreatic homogenate. Pancreatic serine proteases, trypsin and
      chymotrypsin, which did not stimulate leukocytes, also generated activity from
      other tissues. Leukocyte pseudopod formation could be significantly inhibited by
      adding the serine protease inhibitor 6-amidino-2-naphthyl p-guanidinobenzoate
      dimethanesulfonate (ANGD) during tissue homogenization (p < 0.001). Injection of
      pancreatic homogenate into rats led to increased plasma hydrogen peroxide levels
      and an instantaneous drop in mean arterial pressure that was often lethal. These
      responses were prevented by prior infusion of ANGD (p < 0.001). Intravital
      microscopy of the rat mesentery confirmed that superfusion of filtered pancreatic
      homogenate leads to significant increases in cell death (p < 0.05), as detected
      by propidium iodide, and hydrogen peroxide formation (p < 0.05), as determined by
      dichlorofluorescein diacetate (DCFH) fluorescence. CONCLUSION: These results
      suggest that pancreatic enzymes attack tissue and generate cellular activators
      that are associated with organ dysfunction in shock.

PMID- 10901498
TI  - Propagation of viral-size particles in lymph and blood after subcutaneous
      inoculation.
AB  - OBJECTIVE: We investigated the propagation of viral-size particles by lymph and
      blood after subcutaneous injection. METHODS: In the canine model, transport of
      [99mTc] sulfur colloid particles of different sizes was studied in different
      settings in venous blood and lymph for 45 minutes after inoculation. RESULTS: The
      mean arrival time of particles in the blood was 2.10+/-0.46 minutes and 8.87+/
      1.72 minutes in the lymph. Lymph flow in the canine leg was 28.79 +/-2.09)
      microl/min and was increased by leg massage. The particle concentration was 1000
      times higher in the lymph fluid than in blood. Particle flux values were
      comparable in blood and lymph. The accumulation of particles in blood initially
      rose faster than in lymph. Accumulation in lymph rises slower but continues
      longer and reaches higher values. Ninety percent of the inoculum remains at the
      injection site for at least 45 minutes. Particle size matters more in blood
      distribution. Leg massage enhances particle transport by lymph. CONCLUSIONS:
      After subcutaneous injection, viral-size particles initially arrive in the blood
      and later in the lymph. Accumulation in lymph and blood increases for a prolonged
      time after inoculation. Results suggest possibilities for limiting the spread of
      infectious matter by early local antiviral treatment.

PMID- 10901499
TI  - Alpha4beta1-integrin activation is necessary for high-efficiency T-cell subset
      interactions with VCAM-1 under flow.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      alpha4beta1-integrin state of activation on CD4+ T-cell subsets and their
      adhesive interaction to VCAM-1 under flow. METHODS: Human CD4+ memory and naive T
      cells were freshly isolated and effector-helper T-cell subsets. Th1 and Th2
      cells, were differentiated in vitro from CD4+ naive T-cells. The expression of
      activation/ligand induced epitopes on beta1-integrins of each T-cell subset was
      assessed using mAb HUTS21 and mAb 15/7. T-cell subsets attachment and rolling on
      VCAM-1 was determined under defined flow conditions and the rates of attachment
      (ka), accumulation, and instantaneous rolling velocities were correlated to their
      beta1-integrin activation epitope expression. RESULTS: A subset of memory T-cells
      constitutively express activation/ligand induced epitopes on beta1-integrins
      recognized by mAb HUTS21 and 15/7, whereas expression levels on naive T-cells is
      low or not detectable. Consistent with an activated phenotype, memory T-cells
      exhibit significantly higher rates of attachment and accumulation on VCAM-1 under
      flow as compared to naive T-cells. Interestingly, the expression of
      activation/ligand induced epitopes on beta1-integrins on Th2 cells and the
      ability of these cells to interact with VCAM-1 are comparable to memory T-cells.
      In contrast, Th1 cells did not interact as efficiently with VCAM-1, which
      correlated with lower expression of activation/ligand induced epitopes on these
      cells. VCAM-1 interactions are inhibited completely by pretreatment of the T
      cells with blocking mAb to alpha4-integrins or beta1-integrins, indicating that
      alpha4beta1 is the predominant T-cell integrin involved. CONCLUSIONS: Memory T
      cells express constitutively active alpha4beta1-integrins, as compared to naive T
      cells, which mediate high rates of initial attachment and sustained high-affinity
      adhesive interactions with VCAM-1 under flow conditions in vitro. Similarly, in
      vitro differentiated Th2 cells but not Th1 cells, which also express elevated
      levels of activated alpha4beta1-integrins, are capable of sustaining high
      affinity adhesive interactions with VCAM-1. The differences observed in beta1
      integrin activation on T-cell subsets may underlie selective recruitment patterns
      of T-cell subsets in vivo.

PMID- 10901500
TI  - Nitric oxide protects venules against histamine-induced leaks.
AB  - OBJECTIVE: The goal of the present study was to investigate the prophylactic role
      of nitric oxide (NO) in the mesenteric microvasculature in preventing
      microvascular leakage subsequent to histamine application, and to evaluate the
      response of mast cells during these conditions. METHODS: Regions of the rat
      mesenteric microcirculation were flushed free of blood and pretreated with either
      the nitric oxide donor sodium nitroprusside (SSP 10(-6) M) or Hepes-buffered
      saline containing 0.5% bovine serum albumin (HBS-BSA) for 15 minutes, then
      exposed to histamine (10(-3) M) for another three minutes. In another set of
      experiments, the microvasculature was treated with either histamine (10(-3) M)
      for three minutes or SNP (10(-6) M) for 15 minutes. A control group was treated
      with HBS-BSA for 15 minutes. RESULTS: The protective role of NO was evaluated by
      its ability to reduce or prevent histamine-induced venular leaks. Mesenteric
      microvessels pretreated with SNP before histamine suffusion showed a significant
      decrease in both area and number of venular leaks following the perfusion of
      fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA). Although SNP
      pretreatment did not reduce the percentage of mast cells that degranulated in the
      presence of histamine, it did somewhat reduce the severity of the degranulation.
      CONCLUSION: This study demonstrated that nitric oxide availability protects
      mesenteric venules against histamine-induced leaks, but does not prevent
      degranulation of mast cells. Therefore, nitric oxide probably acts directly on
      venular endothelial cells to prevent leak formation.

PMID- 10901501
TI  - The results of the GISSI-Prevenzione trial in the general framework of secondary
      prevention.

PMID- 10901502
TI  - Electrocardiographic risk stratification in dilative cardiomyopathy: an
      unfulfilled promise.

PMID- 10901503
TI  - QT dispersion: time for an obituary?

PMID- 10901504
TI  - C-reactive protein, inflammation and atherosclerosis: do we really understand it
      yet?

PMID- 10901505
TI  - Assessment of myocardial viability: guide to prognosis and clinical management.

PMID- 10901506
TI  - Cell adhesion molecules, simvastatin and hormone replacement therapy, in coronary
      artery disease.

PMID- 10901507
TI  - Is SHORT hospital treatment safe for patients with acute myocardial infarction?

PMID- 10901508
TI  - Homocysteine and atherothrombosis--mechanisms for injury.

PMID- 10901509
TI  - Cell adhesion molecules in relation to simvastatin and hormone replacement
      therapy in coronary artery disease.
AB  - AIMS: To assess the effect of simvastatin, hormone replacement therapy and their
      combination on soluble cell adhesion molecules and plasma lipids, in
      hypercholesterolaemic post-menopausal women with coronary artery disease.
      METHODS: We studied 16 post-menopausal women with coronary artery disease and
      hypercholesterolaemia (total cholesterol >200mg x dl(-1) and LDL cholesterol >130
      mg x dl(-1)). We compared simvastatin (20 mg daily) with hormone replacement
      therapy (0.625 mg conjugated oestrogen and 2.5 mg medroxyprogesterone acetate
      daily) and their combination, in a randomized, crossover, placebo controlled
      study. Each treatment period was 8 weeks long with a 4 week washout interval
      between treatments. Circulating cell adhesion molecules and plasma lipids were
      evaluated at the end of each treatment period. RESULTS: All three active
      treatments--simvastatin, hormone replacement therapy and the combination therapy-
      significantly reduced total and LDL cholesterol, compared to placebo (P<0.001).
      Only hormone replacement therapy, alone and in combination with simvastatin,
      significantly decreased lipoprotein(a) when compared to placebo (P<0.05), whereas
      simvastatin had no significant effect. Likewise, hormone replacement therapy and
      the combination therapy significantly reduced the intercellular adhesion molecule
      (ICAM-1) plasma levels (P=0.03 and P=0.02, respectively), while simvastatin,
      which was superior to hormone replacement therapy in lowering total and LDL
      cholesterol, did not modify ICAM-1 levels; the combination therapy was not more
      effective than hormone replacement therapy alone in ICAM-1 reduction. Neither the
      effect, on any treatment when compared to placebo, of VCAM-1 nor E-selectin
      levels differed significantly. CONCLUSIONS: Hormone replacement therapy may limit
      the inflammatory response to injury by modulating the expression of cell adhesion
      molecules from the endothelial cells, possibly in association with lipoprotein
      (a) reduction.

PMID- 10901510
TI  - Head to head comparison of dobutamine-transoesophageal echocardiography and
      dobutamine-magnetic resonance imaging for the prediction of left ventricular
      functional recovery in patients with chronic coronary artery disease.
AB  - AIMS: A substantial number of patients with dysfunctional but potentially viable
      myocardium cannot be accurately evaluated by transthoracic echocardiography due
      to a poor acoustic window. This study compares the diagnostic value of
      alternative functional imaging techniques, such as dobutamine-transoesophageal
      echocardiography (dobutamine-TEE) and dobutamine magnetic resonance imaging
      (dobutamine-MRI) for the detection of viable myocardium and the prediction of
      left ventricular functional recovery in patients with chronic coronary artery
      disease following successful revascularization procedures. METHODS AND RESULTS:
      Rest and low-dose (5, 10 microg dobutamine x min(-1) x kg(-1)) multiplane
      dobutamine-TEE and ultrafast cine-MRI studies were performed in 103 patients.
      Contractile recovery of an infarct region was predicted if a dobutamine
      contraction reserve could be assessed visually by TEE or MRI in > or =50% of
      infarct-related a- or dyskinetic segments. Revascularization of the infarct
      related vessel was successful in 88 patients, and 4.9 +/- 0.7 months later 52
      patients still had an angiographically controlled open target vessel. These
      patients underwent another rest MRI study to assess left ventricular functional
      recovery. A dobutamine contraction reserve was observed in 27/52 (52%) patients
      by TEE and in 26/52 (50%) patients by MRI. Functional improvement of the infarct
      region was diagnosed in 28/52 (54%) patients. The positive and negative
      predictive accuracy of dobutamine-TEE and dobutamine-MRI for the prediction of
      left ventricular functional recovery was not significantly different (85% vs 92%,
      ns and 80% vs 85%, ns). Diagnosis of a predominantly viable infarct region by TEE
      and MRI predicted a significant increase in left ventricular ejection fraction
      (TEE: 12 +/- 8% vs 2 +/- 7% P<0.001, MRI: 13 +/- 7% vs 2 +/- 7%, P<0.001)
      compared to infarct regions graded as scar. CONCLUSION: A qualitative visual
      analysis of TEE and MRI viability studies is highly accurate for the prediction
      of left ventricular functional recovery in patients with dysfunctional myocardium
      and proved to be a clinically valuable alternative if transthoracic dobutamine
      echocardiography is unsuitable. To date, TEE is cardiologists' preferred choice
      for the assessment of myocardial viability but MRI may become significantly more
      attractive with increasing local availability and experience.

PMID- 10901511
TI  - Prospective study of early discharge after acute myocardial infarction (SHORT)
AB  - AIMS: To identify, without additional investigation, a large group of myocardial
      infarction patients at low risk who would qualify for early discharge. METHODS:
      The decision rule was developed in 647 unselected patients with consecutively
      admitted myocardial infarction, and validated in 825 others. Daily event-rates
      were calculated for major (death, ventricular fibrillation, recurrent infarction,
      heart failure, advanced AV-block) and minor (unstable angina and rhythm
      abnormalities) cardiac complications. RESULTS: Patients free from major
      complications until day 7 (44% of all patients) were found to constitute a very
      low risk group and thus would qualify for discharge at day 7. Of the 39% of
      patients with an uncomplicated infarction (low risk) in the validation group, 31%
      were discharged at day 7, while 8% stayed longer because of non-cardiac co
      morbidity, for social reasons or logistic problems. No major adverse event
      occurred within 7 days after hospital discharge and only 1.8% developed
      complications within 1 month. The median duration of hospital stay for all in
      hospital survivors was 7 days compared to 10 days in the control group.
      CONCLUSION: Prospective application of the early discharge decision rule, based
      upon simple clinical variables and without the need for additional non-invasive
      and/or invasive tests, resulted in a significant reduction of hospital stay. The
      decision rule correctly classified patients into high and low risk groups and
      appeared feasible and safe. Its efficacy was demonstrated by its ability to
      identify a large group of post infarction survivors at low risk for complications
      during follow-up.

PMID- 10901512
TI  - C-reactive protein and the severity of atherosclerosis in myocardial infarction
      patients with stable angina pectoris.
AB  - BACKGROUND: Recent findings provide evidence for the importance of inflammatory
      processes in the pathogenesis of atherosclerosis. C-reactive protein was elevated
      in patients with peripheral artery disease, coronary heart disease and myocardial
      infarction compared to normal subjects. METHODS: In 1112 male and 299 female
      survivors of myocardial infarction (mean age +/- SD, men, 50.4 +/- 9.5, women,
      56.1 +/- 9.3), we investigated whether plasma C-reactive protein concentration is
      associated with the severity of coronary heart disease and generalized pre
      clinical or clinically manifest arteriopathy. The control group consisted of 326
      male and 138 female individuals matched for age without clinical symptoms of
      coronary disease. The severity of arteriosclerotic changes was determined for the
      extra-cranial brain-supplying arteries, abdominal aorta, pelvis and leg arteries.
      In myocardial infarction patients coronary angiography was performed. Laboratory
      analyses included determination of C-reactive protein, fibrinogen, D-dimer, HDL
      cholesterol, LDL-cholesterol and triglycerides. RESULTS: The following ranking of
      C-reactive protein concentrations was found: controls < or = patients after
      myocardial infarction without atherosclerosis < or = patients with myocardial
      infarction and pre-clinical atherosclerosis < or = patients with myocardial
      infarction and clinically manifest atherosclerosis. Additionally, our data showed
      a significant association between C-reactive protein concentrations and the
      angiographically detected degree of coronary heart disease. CONCLUSIONS: As C
      reactive protein is a marker of inflammatory processes, our results in patients
      with clinically manifest and early pre-clinical atherosclerosis support the
      hypothesis that inflammatory processes in the vessel wall participate in
      atherogenesis. Moreover, they support the hypothesis of a causal relationship
      between an acute phase reaction and the pathogenesis of atherosclerosis in
      coronary arteries and other parts of the arterial vessel system.

PMID- 10901513
TI  - Plasma adrenomedullin, a new independent predictor of prognosis in patients with
      chronic heart failure.
AB  - BACKGROUND: Adrenomedullin, a potent endogenous vasodilating and natriuretic
      peptide, may play an important role in the pathophysiology of chronic heart
      failure. Plasma levels of immunoreactive adrenomedullin were examined for
      prediction of prognosis in chronic heart failure. METHODS AND RESULTS: Plasma
      levels of immunoreactive-ADM (ir-ADM) were measured by radioimmunoassay in 117
      chronic heart failure patients with idiopathic or ischaemic cardiomyopathy (mean
      ejection fraction: 28 +/- 10%, in the NYHA functional class
      I/II/III/IV:8/73/29/7, and treated with ACE inhibitors and diuretics. Plasma
      levels of immunoreactive adrenomedullin were significantly increased in chronic
      heart failure patients by comparison to controls (618 +/- 293 pg x ml(-1) vs 480
      +/- 135 pg x ml(-1), P=0.01). During the follow-up period (237 +/- 137 days) 14
      cardiovascular deaths and four urgent cardiac transplantations occurred. In the
      univariate Cox model, immunoreactive adrenomedullin plasma levels were related to
      prognosis (P=0.004). A multivariate analysis including heart rate, systolic blood
      pressure, NYHA class, left ventricular ejection fraction, left ventricular
      echocardiographic end-diastolic diameter, plasma levels of immunoreactive
      adrenomedullin, endothelin-1, norepinephrine and atrial natriuretic peptide was
      performed: plasma levels of immunoreactive adrenomedullin (P=0.03), of endothelin
      1 (P=0.0001), and systolic blood pressure (P=0.003) were significantly associated
      with outcome. CONCLUSION: Our results suggest that elevated plasma levels of
      immunoreactive adrenomedullin are an independent predictor of prognosis in
      predominantly mild to moderate chronic heart failure treated by conventional
      therapy and provide additional prognostic information.

PMID- 10901514
TI  - Predictive value of wavelet decomposition of the signal-averaged
      electrocardiogram in idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Wavelet decomposition of the signal-averaged electrocardiogram has
      been proposed as a method of detecting small and transient irregularities hidden
      within the QRS complex and of overcoming some of the limitations of time domain
      analysis of the signal-averaged electrocardiogram. AIM: This study evaluated the
      potential utility of wavelet decomposition analysis in the risk stratification of
      patients with idiopathic dilated cardiomyopathy. METHODS AND RESULTS: Both
      wavelet decomposition and time domain analysis were applied to the signal
      averaged electrocardiogram recordings of 82 patients with idiopathic dilated
      cardiomyopathy (mean age 43 +/- 14 years, 60 men) and 72 normal controls (mean
      age 44 +/- 15 years, 48 men). Three conventional time domain indices and four
      wavelet decomposition analysis parameters (QRS length, maximum count, surface
      area, and relative length) were derived from each recording using a Del Mar CEWS
      system and an in-house software package, respectively. The results showed that
      (1) more patients with idiopathic dilated cardiomyopathy than without had late
      potentials, and that the filtered QRS duration was significantly longer in
      patients than in controls (P<0.001). Similarly, abnormal wavelet decomposition
      analysis was more common in patients and wavelet decomposition measurements were
      significantly different between patients and controls (P<0.01); (2) conventional
      time domain analysis did not distinguish between clinically stable patients and
      patients who developed progressive heart failure, or between patients with and
      without arrhythmic events; (3) wavelet decomposition analysis identified patients
      who went on to develop progressive heart failure but failed to distinguish
      patients with arrhythmic events from those without; (4) survival analyses of a
      mean follow-up of 23 months showed that patients with late potentials tended to
      develop progressive heart failure more frequently than others (P=0.06). Patients
      with an abnormal wavelet decomposition result more frequently developed
      progressive heart failure than those with a normal wavelet decomposition result
      (P=0.027); (5) in a univariate analysis (Cox model), wavelet decomposition
      measurements but not time domain indices significantly correlated with the
      development of progressive heart failure (P=0.01). Multivariate analysis showed
      that only left ventricular end-diastolic dimension and peak oxygen consumption
      during exercise remained significant predictors of progressive heart failure.
      CONCLUSION: Wavelet decomposition analysis of the signal-averaged
      electrocardiogram is superior to conventional time domain analysis for
      identifying patients with idiopathic dilated cardiomyopathy at increased risk of
      clinical deterioration. Wavelet decomposition analysis, however, is unlikely to
      prospectively distinguish patients at a high risk of arrhythmic events in
      idiopathic dilated cardiomyopathy in its present form.

PMID- 10901515
TI  - Acute psychological stress and the propensity to ventricular arrhythmias;
      evidence for a linking mechanism.
AB  - AIMS: This study was designed to test the hypothesis that acute psychological
      stress is capable of inducing an increase in the dispersion of repolarization in
      patients with underlying coronary artery disease. METHODS AND RESULTS: Twenty
      four patients undergoing elective coronary angiography were studied, 17 with
      significant coronary artery disease and seven with normal coronary arteries.
      Following coronary angiography they were subjected to a series of timed cognitive
      tests, well known to induce acute psychological stress. An individual's
      perception of stress was assessed by visual analogue scales. Serial ECGs were
      recorded during the cognitive tests and QT, QRS and JT intervals measured from
      which QT, QRS and JT dispersion were calculated. Psychological stress was
      reported by the seven patients with normal coronaries and 14 of the 17 with
      coronary artery disease. In patients who experienced stress a marked increase in
      QT dispersion, reflecting JT dispersion, was observed in those with coronary
      artery disease (F=22.4, P=0.0001) but not in those without. At baseline there was
      no difference in QT dispersion between those with and without coronary artery
      disease (27-57 ms, 17-53 ms, P > or = 0.5). CONCLUSION: Acute psychological
      stress induces an increase in QT dispersion in patients with underlying coronary
      artery disease due to changes in JT dispersion (rather than QRS dispersion). This
      suggests that psychological stress modifies the dispersion of repolarization
      through ischaemia related changes in action potential duration.

PMID- 10901516
TI  - Bilateral internal thoracic artery operations in the elderly.
AB  - BACKGROUND: Elderly surgical patients have higher operative morbidity and
      mortality than younger cohorts, particularly when the procedure is lengthy and
      complex. While use of bilateral internal thoracic arteries (BITA) is often
      associated with increased surgical risk, we nevertheless hypothesized that the
      use of BITA in elderly coronary artery bypass patients would not significantly
      increase their operative risk beyond that encountered using single internal
      thoracic arterial (SITA) or saphenous vein grafts (SVG). We maintained that
      arterial grafts remain essentially unaffected by arteriosclerosis, and that
      extension of a high-quality life is a desirable outcome regardless of age at
      operation. METHODS:  EXPERIMENTAL DESIGN: We studied myocardial revascularization
      in 673 patients over 65 years of age at the time of operation. All operations
      were conducted or supervised by a single surgeon during a ten-year period from
      January 1986 to January 1996. Preoperative and operative dates were recorded
      prospectively. SETTING: All patients underwent coronary artery bypass grafting.
      INTERVENTIONS: The study compared outcomes in patients having all veins, SITA or
      BITA operations. For the first analysis, 673 patients were divided into three
      groups: 163 patients (Group 1) had saphenous vein used for all bypasses; 338
      patients had a SITA with supplemental vein grafts (Group 2); and 172 patients
      (Group 3) had BITAs with additional vein grafts as needed. In the second
      analysis, Group 3 was subdivided and grouped by the coronary arteries which
      received the ITA grafts, and the analysis was repeated. One hundred and sixteen
      patients (Group 3A) underwent traditional placement of ITA bypasses (left ITA to
      the LAD, right ITA to the RCA); in Group 3B, 56 patients received
      revascularization of branches of the left coronary artery (left ITA to the
      circumflex system, right ITA to the LAD). MEASURES: We communicated directly with
      90.5% of the patients, their families, or their physicians. The survival status
      of the remainder was determined through the National Social Security Death Index
      Network. This allowed us to obtain follow-up longevity data for 100% of the study
      sample at a mean observation period of 5.03+/-3.1 years with variation between
      10.8 years to 2.4 years. RESULTS: A multivariate analysis showed that placement
      of both ITA grafts to left-sided arteries in older patients independently
      improved long-term survival (p=0.031). CONCLUSIONS: The BITA procedure does not
      have greater operative morbidity or mortality in the elderly despite the length
      or complexity of the surgery. To realize improved long-term survival rates,
      however, both ITAs must be grafted to the left coronary artery branches.

PMID- 10901517
TI  - Association of osteopontin with calcification in human mitral valves.
AB  - BACKGROUND: Little is known about the long-standing inflammation leading to
      calcification within heart valves. Osteopontin, a phosphorylated glycoprotein, is
      present within atheromatous calcific plagues in response to vascular endothelial
      injury. The purpose of the study was to investigate whether osteopontin exists in
      calcific mitral valve leaflets in human beings, and to determine a link between
      chronic inflammation leading to mitral stenosis and the osteopontin status of
      mitral valvular tissue. MATERIALS AND METHODS: We reviewed the case histories of
      17 patients who underwent mitral valve replacement therapy for mitral stenosis
      between 1995 and 1997 (8 men and 9 women, mean age 61 years). Hybrid mouse
      monoclonal immunoglobulin G1 antibodies were used for immunohistochemical
      detection of osteopontin in the acetone-fixed specimen. The control group
      consisted of normal mitral valve tissue from cardiomyopathy patients who
      underwent cardiac transplantation. RESULTS: A weak osteopontin immunoreactivity
      was present in apparently normal mitral valve tissue obtained from cardiomyopathy
      patients. All mitral stenosis patients had immunoreactivity (17/17) for
      osteopontin within calcific deposits of mitral valve tissue. The intensity of
      osteopontin activity had a strong association with increasing macrophage and
      calcium aggregations in the mitral valvular tissue. We found no correlation
      between osteopontin status and clinical features on the prognosis of calcific
      mitral stenosis. CONCLUSIONS: We conclude that osteopontin coexists with intimal
      macrophages in calcific human mitral valve tissue. Demonstration of such
      association between the presence of osteopontin and calcification in human mitral
      valves is consistent with the hypothesis that calcification in this tissue is, at
      least in part, an actively mediated phenomenon.

PMID- 10901518
TI  - Left main coronary artery stenosis: early experience with surgical
      revascularization without cardiopulmonary bypass.
AB  - BACKGROUND: To determine the safety of surgical revascularization without
      cardiopulmonary bypass (CPB) in left main stem (LMS) coronary stenosis. METHODS
      AND RESULTS: Between October 1996 and April 1998, 67 consecutive patients with a
      > or =50% LMS stenosis underwent coronary revascularization without bypass (BH)
      and were compared to a contemporary group of 160 patients revascularized with
      conventional bypass (CPB). Mean ages in both groups were similar: 63.1 and 64.5
      years in BH and CPB groups respectively (p=0.91). Significant triple vessel
      disease occurred in 40 (80%) and 75 (47.5%) patients in BH and CPB groups
      respectively (p=NS). Average grafts per patient was numbered 3.1 in BH group and
      2.9 in CPB group (p=NS). The perioperative infarction rate (defined arbitrarily
      as a CK-MB >100 U/l) was 4% (2 patients, excluding 1 preoperative infarct) and
      3.1% (5 patients, excluding 2 preoperative infarcts) in groups BH and CPB
      respectively (p=0.28). Postoperative blood transfusion requirements were less in
      BH group (19 patients, 38%) compared to CPB group (103 patients, 64.4%),
      (p=0.04). Postoperative inotropic requirements were similar in both groups; BH
      group (15 patients, 30%) and CPB group (72 patients, 45%). Mean hospital stay was
      6.4 and 7.6 days in BH and CPB groups respectively (p=0.49). The hospital
      mortality rate was 0% and 3.8% (6 patients) in BH and CPB groups respectively
      (p=NS). CONCLUSIONS: Our early experience suggests that non-CPB surgical
      revascularization in LMS stenosis is a feasible and safe alternative to
      conventional cardiopulmonary bypass.

PMID- 10901519
TI  - "Mosaic" medtronic bioprosthetic valve replacement clinical results and
      hemodynamical performance.
AB  - BACKGROUND: We report the mid-term results of a prospective trial of a new
      bioprosthetic valve. The Mosaic bioprosthesis consists of porcine aortic valve
      that has been cross linked ed in glutaraldehyde solution under zero-pressure
      fixation and treated with alpha amino oleic acid to reduce the potential for
      calcification. METHODS: Mosaic bioprosthetic valve replacement was performed in
      67 consecutive patients between January 1995 and August 1998. There were 37
      patients having aortic valve replacement (AVR) and 30 having mitral valve
      replacement (MVR) who entered this study. The patients age ranged 56 to 86 years
      (mean 74.9); 38 were female and 29 were male; 44 were in NYHA grade 3 and 21 were
      NYHA grade 4. All mitral valve replacements were performed with total
      preservation of subvalvular apparatus. Echocardiographic assessment of valve and
      LV function were performed on 7th day, 6 months 1,2 and 3 years. RESULTS: There
      was no hospital mortality. 3 year survival was 85.9+/-5.9% for AVR and 100% for
      MVR. Freedom from antithromboembolic related haemorrhage has been 96.7% for MVR
      and 91.9% for AVR. Freedom from the transient neurological event was 96.7+/-3.3%
      for MVR and 100% for AVR Freedom from structural valve failure, permanent
      thromboembolism, thrombosis or endocarditis has been 100% for both AVR and MVR.
      In AVR group left ventricle mass, left ventricle mass index significantly
      decreased, when cardiac index and effective orifice area increased significantly
      during study period. Transvalvular gradient did not change. In MVR group
      transvalvular gradient, effective orifice area and cardiac index did not change.
      CONCLUSIONS: The valve was user friendly. The early results are very
      satisfactory. Echocardiography measurements after aortic valve replacement are
      showing very marked late postoperative remodelling of left ventricle. After
      mitral valve replacement there were exceptionally low transvalvular gradients, no
      left ventricle outflow tract obstruction.

PMID- 10901520
TI  - Early and late results of mitral valve repair for mitral valve regurgitation.
      Significant risk factors of reoperation.
AB  - BACKGROUND: Mitral valve repair for mitral valve regurgitation has many
      advantages over mitral valve replacement. However, durability and reoperation
      after mitral valve repair still remain major problems. We examined the outcome of
      mitral valve repair for mitral valve regurgitation and analyzed several pre- and
      intraoperative potential risk factors to determine the significant risk factors
      of reoperation. METHODS: From February 1981 to November 1996, 86 patients
      underwent mitral valve repair for mitral regurgitation or combined mitral
      regurgitation and stenosis. The mean age was 53 years, and 88.4% were New York
      Heart Association class III or IV. The causes of mitral valve disease were
      degenerative disease in 53 patients, rheumatic disease in 15, infective
      endocarditis in 11, and ischemic disease in 7. There were 2 early and 8 late
      deaths. RESULTS: Actuarial overall survival including early death at 10 years was
      83.2+/-6.1%, freedom from reoperation was 86.8+/-5.3%, freedom from
      thromboembolism was 90.9+/-6.2%, and freedom from infective endocarditis was
      98.5+/-1.5%. There was no bleeding event. At the last follow-up, most patients
      were in New York Heart Association class I or II. Prolapse of anterior leaflet
      and rheumatic mitral regurgitation were identified as independent predictors for
      reoperation. CONCLUSIONS: The repair techniques for anterior leaflet prolapse and
      patient selection in rheumatic mitral disease are important for improving long
      term results of mitral valve repair for mitral regurgitation.

PMID- 10901521
TI  - Patterns of systolic stress distribution on mitral valve anterior leaflet chordal
      apparatus. A structural mechanical theoretical analysis.
AB  - Increasing diffusion and complexity of mitral valve repair procedures may prompt
      an interest in the evaluation of the patterns of stress distribution on the
      chords, which are, from the structural mechanical point of view, the weakest
      element of valve apparatus. This theoretical analysis concentrates in particular
      on the mitral valve anterior leaflet. As is known, the vast majority of the
      chordae are attached to the anterior leaflet within the coaptation area; during
      systole they are then necessarily parallel, aligned along the same plane as that
      of the leaflets' coaptation surface, to which they are attached; moreover the
      thickness of the chordae increases significantly from the marginal chordae to the
      more central ones. In normal conditions during systole the progressively wider
      coaptation surface causes the increasing stress to be supported by an increasing
      number of progressively thicker chords, which are substantially parallel and
      aligned on the coaptation surface plane in such a way that they can share the
      stress between them, according to their thickness; in other words chords form a
      multifilament functional unit which enrolls elements of increasing thickness in
      response to the mounting stress. The geometrical modifications of the valve
      apparatus architecture (annulus dilatation, leaflet retraction, chordal
      elongation or retraction) often associated with valve insufficiency due to
      chordal rupture, have the common result of causing, during systole, a radial
      disarrangement of the direction of most of the secondary chordae which are no
      longer parallel, aligned on the coaptation surface plane. Due to the negligible
      elastic module of the valve leaflet, in this new arrangement the various chordae
      cannot share the stress between themselves as they do in a normal physiological
      situation; on the contrary the thinner chordae nearer to the free margin are also
      loaded with the peak systolic stress, thus generating conditions favoring their
      rupture. It can, therefore, be hypothesized that the anatomopathological picture
      of valve insufficiency due to chordal rupture may be the final event of a series
      of geometrical modifications of valve apparatus architecture, the common
      consequence of which is to load thinner marginal chords with peak systolic stress
      from which they are normally spared, thus favoring their rupture.

PMID- 10901522
TI  - Acute renal failure requiring hemodialysis immediately after heart
      transplantation portends a poor outcome.
AB  - BACKGROUND: Previous studies have not provided a definite clarification for the
      predictive value of pretransplant renal indices on postcardiac transplant patient
      outcome. Therefore, the purpose of this study was to investigate the interaction
      between pretransplant renal function and recovery after heart transplantation.
      METHODS: The study group consisted of 199 consecutive patients who underwent
      heart transplantation between 1973 and 1994. For better comparison, patients were
      arbitrarily divided into three different groups based on the year of the
      transplant operation: Group I- before 1985 (n=13), Group II- between 1985 and
      1989 (n=68) and Group III- between 1990 and 1994 (n=118). Values for serum
      creatinine (Cr), blood urea nitrogen (BUN), urea/creatinine ratio (U/Cr),
      creatinine clearance (Cr(cl)), length of hospital stay (LOS), early (30-day)
      mortality, and survival at 1-year and at 5-year were collected for each patient.
      The data was analyzed by the use of univariate log-rank test with forward
      stepwise procedure. RESULTS: Postcardiac transplant LOS in the hospital or
      survival was unaffected by the pretransplant renal indices except the U/Cr ratio
      (p>0.05). When adjusted for the time, the U/Cr ratio was also insignificant
      (p=0.1349). The use of hemodialysis was necessary in 9 patients (4.5%) for
      treatment of acute renal failure manifested immediately after the transplant
      operation. Early mortality was 44% for these 9 cardiac transplant recipients who
      required the use of hemodialysis: 0% (0/3) in the 1985-1989 period and 67% (4/6)
      in the 1990-1994 period. CONCLUSIONS: Pretransplant renal indices have no
      predictive value on outcome after a heart transplant operation, however,
      postcardiac transplant acute renal failure necessitating hemodialysis portends a
      poor outcome.

PMID- 10901523
TI  - Inflammatory response during simulated extracorporeal circulation with addition
      of nitric oxide.
AB  - BACKGROUND: Heart operations performed with extracorporeal circulation (ECC) are
      associated with an inflammatory response. This response is partially due to
      granulocyte activation. Leukocyte derived free radicals are involved in tissue
      injury. The purpose of this study was to observe whether nitric oxide influence
      the inflammatory response during simulated ECC. METHODS: In a model of simulated
      extracorporeal circulation, fresh whole human blood mixed with Ringer's solution
      was circulated through a heart-lung machine for three hours. In five circuits NO
      was added to oxygen/air mixture (group N), while five other circuits were
      ventilated with oxygen/air mixture (group C). The methods for estimating the
      inflammatory response were determination of oxygen free radicals production
      capacity, using chemiluminescence, and measurements of concentration of
      granulocyte derived proteins (myeloperoxidase and human neutrophil lipocalin).
      RESULTS: All measured parameters were similarly independent of additional supply
      of nitric oxide almost throughout extracorporeal circulation time. The sole
      significant difference between the two groups was found at an early stage of
      extracorporeal circulation, when luminol-enhanced chemiluminescence in whole
      blood was higher in the N group (1,500, 1,470-1,950 vs 1,038, 750-1,050 in the
      control group; medians with quartiles). A similar tendency was observed in
      lucigenin-enhanced chemiluminescence at 60 min of extracorporeal circulation
      (625, 560-875 in the N group vs 400, 360-525 in the control group; medians with
      quartiles). CONCLUSIONS: Nitric oxide supply does not influence inflammatory
      response during three hours long extracorporeal circulation, although some
      protective effect on hydrogen peroxide production in whole blood was detected in
      the initial phase of extracorporeal circulation.

PMID- 10901524
TI  - Pre-existing elevated pulmonary vascular resistance: long-term hemodynamic follow
      up and outcome of recipients after orthotopic heart transplantation.
AB  - BACKGROUND: Elevation of pulmonary vascular resistance (PVR) has been considered
      to predict a bad outcome after orthotopic heart transplantation (HTx). A
      transpulmonary gradient (TG) > or =15 mmHg and PVR > or =5 wood (w) are
      correlated with a three-fold increase in 2-days as well as 30-days and 6-, 12
      month mortality. METHODS: We performed a retrospective analysis of 400
      consecutive transplanted patients (pts) on hemodynamic data over a time period of
      3.5 years. In 83 pts (23%) preoperative PVR was > or =5 w and TG >15 mmHg.
      Vasodilator studies were performed in this group of pts in order to evaluate
      pulmonary vasoreactivity or hemodynamic improvement. RESULTS: Hemodynamic follow
      up post-transplantation showed a significant (p<0.001) decrease in mean TG to 8.8
      mmHg within the first, 7.7 after the fifth year as well as decrease in PVR from
      5.5 to 1.6, within the first and fifth year post-transplantation. Compared to the
      control group (n=286) (re-transplants n=6 and pediatric pts n=25 excluded) pts
      with TG <15 mmHg and/or PVR <5 w, transplanted within the same period, 30-day
      mortality and cumulative survival after 1 and 5 years do not show any significant
      difference with a mortality of 3%, 22% and 33% (p<0.05). Subgroup analysis for
      pts with endstage of ischemic versus dilatative cardiomyopathy has not shown any
      significant difference in mortality. CONCLUSIONS: In a retrospective analysis of
      400 pts elevated PVR does not predict a bad outcome after orthotopic heart
      transplantation in early and late mortality.

PMID- 10901525
TI  - Postoperative oxygenation following coronary artery bypass grafting. A
      multivariate analysis of perioperative factors.
AB  - BACKGROUND: Pulmonary oxygenation is generally temporarily impaired following
      cardiac surgery. We studied the factors influencing postoperative oxygenation
      using multivariate analysis. METHODS: This study was retrospectively performed in
      University hospital. Fifty patients undergoing solitary coronary artery bypass
      grafting were included in this study. Patients were divided into two groups by
      mean age; older group (n=25) and younger group (n=25). Alveolar-arterial oxygen
      difference (A-aDO2) and respiratory index (RI) were measured at 3 hours after
      surgery and on postoperative day 1. Statistical analysis was performed using
      forward selection stepwise regression of 12 perioperative variables. RESULTS: In
      all patients, A-aDO2 and RI significantly (p<0.01) increased after surgery and
      remained high on POD1. In stepwise regression analysis, preoperative A-aDO2 and
      RI were significant factors in the equations for postoperative A-aDO2 and RI in
      general, which was the most important factor in the older group. In the older
      group, preoperative A-aDO2 or RI and water balance were significant (p<0.05)
      factors which were responsible for half the oxygenation impairment just after
      surgery, and PCWP showed a significant (p<0.01) negative correlation with both A
      aDO2 and RI on POD1. In the younger group, PCWP was a significant (p<0.01) factor
      for A-aDO2 and CVP and CI were significant for RI on POD1. CONCLUSIONS:
      Postoperative oxygenation was mainly influenced by the preoperative respiratory
      condition, especially in old patients, indicating that preoperative management by
      a physiotherapist may be necessary. Pleurotomy also had a negative influence.
      Careful intraoperative and postoperative volume control is important in old
      patients.

PMID- 10901526
TI  - Surgical results of Stanford type B aortic dissection. Comparisons between
      partial and subtotal replacement of the dissected aorta.
AB  - BACKGROUND: Surgical results for Stanford type B aortic dissection were
      retrospectively compared between the subtotal prosthetic replacement of the
      thoracoabdominal dissected aorta (STR) and partial replacement of the descending
      aorta at the intimal tear (PR). METHODS: Twenty-two patients (11 males and 11
      females with mean age of 56.9+/-2.6 years) undergoing repair of aneurysms were
      analyzed. All operations were performed with the aid of femorofemoral partial
      cardiopulmonary bypass. Reconstruction of the critical artery for spinal cord
      blood supply was determined by evoked spinal cord potential (ESP) monitoring in
      non-urgent cases. Operative mortality and incidence of complications were
      compared between the PR group (Group I; n=15) and the STR group (Group II; n=7).
      RESULTS: There were one operative death and one late death in Group I. No early
      or late deaths occurred in Group II. Postoperative paraplegia occurred in 1
      patient in Group I and 2 patients in Group II. Among patients undergoing
      selective reconstruction of the critical intercostal arteries, paraplegia
      occurred in only one patient. Incidence of postoperative complications was not
      significantly different between Group I and Group II. Presence of rupture
      (p<0.001) and development of acute renal failure (p<0.05) revealed significant
      determinants of postoperative mortality by multivariate analysis. Operative
      procedure did not influence postoperative mortality or occurrence of paraplegia.
      CONCLUSIONS: Operative results of STR with selective reconstruction of the
      critical arteries and PR for aortic dissection were comparable. Subtotal
      replacement of the thoracoabdominal dissected aorta is encouraged to apply for
      patients with diffuse, large postdissection aneurysms or those with a high risk
      of future enlargement of remaining false channels such as Marfan syndrome, under
      adequate reconstruction of the critical segmental arteries.

PMID- 10901528
TI  - Primary closure of deep sternal wound infection following open heart surgery: a
      safe operation?
AB  - BACKGROUND: Deep median sternotomy wound infection is a significant source of
      morbidity and mortality after cardiac operations. Management of an infected
      median sternotomy incision is a subject of controversy. The aim of this study was
      to assess our experience with primary closure without any irrigation system for
      infected deep median sternotomy wound. METHODS: Between January 1994 and December
      1997, 4,227 consecutive open heart procedures via a median sternotomy under
      cardiopulmonary bypass were performed in our department. A total of 27 (0.64%)
      consecutive patients with deep sternotomy wound infection were identified. The
      mean age of the patients was 45 years. Six were female and 21 were male. RESULTS:
      The incidence of deep sternal wound infection was therefore 0.64%. The mean
      duration between the primary operation and the onset of deep sternal wound
      infection was 2.5 weeks. Staphylococcus aureus and Staphylococcus epidermidis
      were the most common pathogen causing postoperative mediastinal infection. Out of
      the 27 cases, 17 were successfully treated, 8 (30%) died and 2 had a persistent
      fistula. The mean follow-up time was 18 months (range 4 to 52 months). The
      mortality in the pediatric group was 4/8 (50%) and 4/19 (21%) in the adult group.
      The mortality for mediastinitis presenting before one week or after 4 weeks after
      operation was 63%. In contrast, the mortality for mediastinitis presenting after
      one week but before 4 weeks after operation was 17%. CONCLUSIONS: Mediastinitis
      after cardiac surgical procedures remains a devastating complication. Primary
      closure without irrigation-suction system should only be considered in selected
      patients.

PMID- 10901527
TI  - Late complications and quality of life after atrial correction of transposition
      of the great arteries in 12 to 18 year follow-up.
AB  - BACKGROUND: Most adolescents and young adults born with transposition of the
      great arteries and survivors of Mustard operation are alive today and are leading
      ordinary lives. How far is the quality of their life influenced by residual
      findings? METHODS: We have analysed the oldest group of 177 children operated on
      with the Mustard procedure during 1979-1984 from our total experience of 609
      corrections of transposition of the great arteries until 1996. In the long-term
      follow-up 12 to 18 years after Mustard operation the clinical investigation, 24
      hours ECG Holter monitoring, 2D and colour flow Doppler echocardiography,
      radionuclide angiocardiography and exercise testing were performed. RESULTS:
      Basic sinus rhythm had 61% of 137 survivors, sinus node dysfunction had 51%. All
      but 4 patients needed no antiarrhythmic therapy. There were 10 sudden deaths.
      Severe tricuspid valve regurgitation developed in 15.9% of children, and
      decreased to 6% after intensive medical treatment. The right ventricular systolic
      dysfunction was found on radionuclide ventriculography in 8% of children after
      surgery. The left ventricular ejection fraction was subnormal in 10% and left
      ventricular diastolic function expressed by rapid filling fraction was subnormal
      in 80% of patients and may cause inability to increase cardiac output at exercise
      The obstruction of caval veins was found in 9%. There were neurological
      complications in 13.3% (10% already preoperatively) but severe brain damage was
      found in 4.4% only. CONCLUSIONS: Exercise tolerance with the maximum oxygen
      consumption over 30 ml/kg/min in 96% of investigated children suggests the good
      ability and full efficiency for recreation sports. Most survivors (84%) are
      reported to lead ordinary lives and function in NYHA class I.

PMID- 10901529
TI  - Mitral valve replacement with small-sized tilting-disc mechanical prostheses may
      lead to moderate stenosis.
AB  - BACKGROUND: Analyzing the hemodynamics of small-sized tilting-disc mechanical
      prostheses implanted in the mitral position. METHODS:  EXPERIMENTAL DESIGN: this
      is a retrospective study. The mean follow-up of patients was 114+/-27 months
      (range 68-152 months). SETTING: departments of Cardiovascular Surgery and
      Cardiology in a general community hospital Patients: this study includes 9
      survivors of 17 patients undergoing mitral valve replacement with this type of
      device between May, 1982 and July, 1991. INTERVENTIONS: all subjects underwent
      mitral valve replacement with size 25 mm Sorin tilting-disc mechanical
      prostheses. MEASURES: all patients underwent transthoracic echocardiography. Five
      consenting patients also underwent transoesophageal echocardiography. The
      following parameters were measured: peak gradient, mean gradient, peak velocity,
      mean velocity, pressure half-time and Doppler area. RESULTS: The ejection
      fraction was 50% or more in all patients. The following mean results were
      obtained: peak gradient: 17.4+/-2.5 mmHg; mean gradient: 8.2+/-0.6 mmHg; peak
      velocity: 2.1+/-0.1 m/sec; mean velocity: 1.43+/-0.06 m/sec; pressure half-time:
      135.9+/-29.7 msec; Doppler area: 1.7+/-0.3 cm2. CONCLUSIONS: Valve replacement
      with Sorin 25 mm tilting-disc mechanical prostheses appears to originate a
      moderate degree of mitral stenosis and, therefore, we do not recommend their use
      if at all possible.

PMID- 10901530
TI  - The diagnosis and management of aortic dissection occurring years after open
      heart surgery.
AB  - Aortic dissection occurring after open heart surgery is an uncommon but well
      recognized complication. Unfortunately, it is associated with a high morbidity
      and mortality. Pre-existing aortic wall pathology, intraoperative aortic
      manipulations and hypertension are known to predispose to the development of this
      condition. We report a case of aortic dissection occurring 2 years after coronary
      artery bypass surgery and complicated by acute saphenous vein graft occlusion and
      severe mitral insufficiency. We review the diagnosis and management of this
      complication.

PMID- 10901531
TI  - Redo Bentall operation for the aortitis syndrome.
AB  - The aortitis syndrome is a chronic inflammatory arterial disease with an unknown
      etiology that may present as a variety of vascular lesions. The surgical
      treatment of aortitis syndrome is associated with many potential difficulties due
      to the inflammatory nature of the disease. A patient with the aortitis syndrome
      underwent the Bentall operation for annulo-aortic ectasia and aortic
      regurgitation 11 years prior to presentation. The operation was not performed
      during the active inflammatory phase. An anastomotic dehiscence required
      reoperation, which was performed with Piehler's method. In the aortitis syndrome,
      the exclusion technique, Carrel patch repair of the coronary arteries and
      pledgeted anastomoses should be performed for aortic root reconstruction.

PMID- 10901532
TI  - Aortobronchial fistula after aortic dissection type B.
AB  - Although rare, aortobronchial fistula complicates thoracic aortic surgery.
      Correct diagnosis and the infectious nature of the lesion are the most important
      conditions to define, for the following best therapy. We presented a case of non
      infectious postsurgical aortobronchial fistula, revealed by computed-tomographic
      scan and angiography procedure, treated with prosthetic graft replacement and
      broad spectrum antibiotic therapy. In the case of infection our policy is
      homograft replacement. Computed tomography, being able to make diagnosis, should
      be performed as the initial technique.

PMID- 10901533
TI  - Tri-foliate pericardial patch repair of supra-valvular aortic stenosis.
AB  - Conventional aortoplasty procedures do not fully restore the normal anatomy in
      supra-valvular aortic stenosis (SVAS), which involves the sinus rim as well as
      the aortic cusps. A tri-sinus repair of this condition is proposed to restore the
      three intercommissural distances to normal and adequately replace the tissue loss
      of the sinuses, for a symmetrical reconstruction of the aortic root. Two
      patients, aged 3 and 11 years, with localized type of supra-valvular aortic
      stenosis were operated, in May 1994 and February 1996. The aortic stenosing ring
      was opened up at three points, by extending the incision into all the three
      sinuses, and the defect was repaired with in situ autologous pericardium, in a
      tri-foliate fashion. This repair achieved a symmetrical reconstruction of the
      aortic root and the systolic pressure gradient was completely abolished.
      Postoperative aortic root angiogram, in the older of the two patients, revealed a
      normal appearing aortic root. The patients have been followed-up for 51 months
      and 30 months respectively. Echocardiography showed competent aortic valves in
      both the patients without any systolic gradient across the aortic valve. A tri
      sinus repair of the aorta in SVAS results in a symmetrical reconstruction of the
      aortic root by restoring the normal intercommissural distances of all the three
      cusps. It also abolishes the systolic pressure gradient. Autologous untreated
      pericardium lends itself easily for tailoring into a tri-foliate patch.

PMID- 10901534
TI  - Carotid endarterectomy prior to major abdominal aortic surgery.
AB  - BACKGROUND: Major aortic surgery carries a high risk of stroke. Carotid artery
      occlusive disease (CAOD) has been identified as one of the contributing risk
      factors. Regarding the long-term prevention of stroke, carotid endartectomy (CEA)
      seems to be superior to the best medical treatment in patients with high-grade
      CAOD. However, the role of CEA prior to major aortic surgery has not been
      studied. METHODS:  DESIGN: Prospective study, observational design. SUBJECTS AND
      SETTING: 201 patients referred to a community hospital for major aortic surgery.
      INTERVENTION: The patients were non-invasively screened by continuous-wave and
      duplex Doppler ultrasonography for the presence of CAOD. In 41 patients with
      angiographically confirmed high-grade CAOD, CEA was performed prior to major
      aortic surgery. MAIN OUTCOME MEASURE: Combined mortality and major morbidity from
      CEA and abdominal aortic surgery. RESULTS: There was no mortality or morbidity
      related to CEA. Total perioperative mortality related to major aortic
      reconstruction was 3.5%. No new perioperative focal neurologic deficits occurred
      except for one fatal stroke in a patient in whom CEA had been judged not to be
      indicated. CONCLUSIONS: CEA can be performed safely prior to major aortic surgery
      resulting in excellent overall neurologic outcome in patients with high-grade
      CAOD. We propose that patients scheduled for major aortic surgery be screened for
      the presence of high-grade CAOD and that CEA be performed first, if indicated
      according to published guidelines.

PMID- 10901535
TI  - Carotid stenosis and abdominal aortic aneurysm at the follow-up examination in
      patients treated for acute extremity ischaemia.
AB  - BACKGROUND: To evaluate survivors treated for acute extremity ischaemia as a risk
      group for carotid stenosis and abdominal aortic aneurysm at the follow-up
      examination. METHODS:  EXPERIMENTAL DESIGN: Clinical study with median follow-up
      of 14 (8-32) months. SETTING: Central Hospital of Central Finland. PATIENTS:
      Eighteen survivors with median age of 77 (51-92) years treated for acute
      extremity ischaemia during two-year period intended to a separate follow-up
      examination median 14 (8-32) months after the acute episode of vascular
      occlusion. Ischaemia was considered as acute in 14 patients and acute on chronic
      in four patients. INTERVENTIONS: Thromboembolectomy was the primary intervention
      excluding two patients with distal upper limb ischaemia who were treated by
      intravenous heparin. MEASURES: Clinical examination, duplex scanning of carotid
      bifurcation and sonography of abdominal aorta were performed at the follow-up
      examination. RESULTS: Significant asymptomatic carotid stenosis >60% was found in
      four patients (22%), two of these patients had significant bilateral carotid
      stenosis. One patient (60%) had abdominal aortic aneurysm of 5.2 cm. CONCLUSIONS:
      In survivors treated for acute extremity ischaemia asymptomatic carotid stenosis
      >60% was found with significantly increased prevalence compared with general
      population and with equal prevalence when compared with patients with peripheral
      vascular disease. Occurrence of abdominal aortic aneurysm was parallel with
      findings in screening surveys.

PMID- 10901537
TI  - Operative management of abdominal aortic aneurysm with left-sided inferior vena
      cava.
AB  - Abdominal aortic aneurysm with left-sided inferior vena cava (IVC) is rare. In
      preoperative examination, it is important to conduct roentgenologic studies and
      determine any venous anomalies. Proximal anastomosis is technically difficult
      because the IVC crosses to the right on the aneurysmal neck. In this case of a 71
      year-old Japanese man, proximal anastomosis was conducted safely under wide vena
      cava mobilization and contraction in the superior direction. In vein resection,
      vessels should be reconstructed because vein communication is not methodical.

PMID- 10901536
TI  - Popliteal-to-distal bypass grafts for critical leg ischaemia.
AB  - BACKGROUND: To assess the value of revascularization to crural and pedal arteries
      using the popliteal artery as inflow source. METHODS:  EXPERIMENTAL DESIGN:
      Retrospective study with a mean follow-up period of 15.2 months (range, 0-46).
      SETTING: Academic referral center. PATIENTS: 62 patients with critical leg
      ischaemia and popliteal artery suitable as inflow source for infrapopliteal
      arterial revascularisation. INTERVENTIONS: 66 popliteal-to-distal bypass
      procedures, of which 18 popliteal-crural bypass grafts and 48 popliteal-pedal
      bypass grafts. MAIN OUTCOME MEASURES: Bypass graft patency, leg salvage, survival
      and success defined as patients alive with leg. RESULTS: At 1-month, 1-year, and
      2-year follow-up, the primary patency rates were 87%, 58%, and 55%, secondary
      patency rates were 95%, 70%, and 67%, leg salvage rates were 97%, 88%, and 88%,
      while 88%, 70%, and 66% of patients were alive with legs at the same intervals.
      At 2-year follow-up the survival rate was 72%. Above-knee popliteal-to-distal
      bypasses achieved better primary patency (p=0.02) and corrected primary patency
      rates (p=0.01) than below-knee popliteal-to-distal bypasses. Diabetes and uraemia
      affected the survival and patients alive with leg rates. CONCLUSIONS: Popliteal
      to-distal bypass surgery is worthwhile for the management of severe, isolated
      infrapopliteal atherosclerotic disease. Diabetic and uraemic patients are at high
      risk for both leg and life loss after revascularisation. Grafts originating from
      the above-knee popliteal artery may achieve better patency rates than those
      originating from the below-knee popliteal artery.

PMID- 10901539
TI  - Aortic dissection and Turner's syndrome.
AB  - Cardiovascular malformations, especially coarctation of the aorta and bicuspid
      aortic valve, are common in patients with Turner's syndrome. Only 46 patients
      with aortic dissection and/or rupture have been described. All patients had
      associated aortic dilation or aneurysm. In all cases except three, involvement of
      the ascending aorta was present, making surgery often imperative. We describe a
      rare case of a DeBakey type IIIb aortic dissection (without involvement of the
      proximal aorta) in a patient with Turner's syndrome mosaicism. The dissection
      occurred two weeks after a caesarean section because of eclampsia. No aortic
      dilation or other cardiovascular malformations were found. The distal extension
      and uncomplicated nature of the dissection indicated medical management. After
      fifteen months of follow-up, she is clinically doing well and repeated CT scan
      shows a stable dissection of the descending and abdominal aorta without dilation.

PMID- 10901538
TI  - Postoperative splanchnic perfusion following the reconstruction of
      thoracoabdominal aortic aneurysm involving abdominal visceral branches. Report of
      a case.
AB  - A 58-year-old man with thoracoabdominal aortic aneurysm involving visceral
      arteries underwent graft replacement of the thoracoabdominal aorta and associated
      reconstruction of abdominal visceral branches. Femoro-femoral extracorporeal
      bypass, intermittent selective visceral arterial perfusion and a staging cross
      clamping method of the aorta were utilized at surgery. The total cross-clamping
      time of the aorta was 165 minutes. The patient's postoperative course was
      uneventful with no incidence of hepatic and renal failure or paraplegia. Although
      postoperative systemic blood pressure and cardiac output recovered to normal
      values within 7 hrs after the release of aortic clamping, it took 18 hrs for
      hepatic venous hemoglobin oxygen saturation (ShvO2) to recover. Base excess in
      arterial blood, lactic acid in arterial and hepatic venous blood, and ketone body
      ratio in arterial blood (AKBR) and hepatic venous blood (HVKBR) recovered to
      within normal ranges after 18 hrs of the release of aortic clamping. ShvO2
      monitoring is a simple and may be a useful parameter in evaluating postoperative
      splanchnic perfusion and predicting abdominal organ failure at the time of
      thoracoabdominal aortic reconstruction involving visceral arteries.

PMID- 10901540
TI  - Vertebral artery surgery with cardiopulmonary bypass and deep hypothermia.
AB  - Deep hypothermia was proposed to prevent neuronal ischemia and stroke during
      surgical procedures on arteries that supply the brain, especially with extended
      occlusive lesions on both internal carotid arteries. The interest of this
      therapeutic option is still under discussion, even in the case of combined
      cardiac and cerebrovascular surgery. We report the case of a 53-year-old male who
      was admitted to our institution for symptomatic vertebrobasilar insufficiency.
      Angiography showed a thrombosis of both internal carotid arteries, stenosis of
      both external carotid arteries, and a tight proximal stenosis of a dominant right
      vertebral artery. Endarterectomy and angioplasty of the origin of the right
      external carotid artery was done first to increase the blood supply to the brain
      via collateral arteries connecting the extra- and intracranial networks. Six
      weeks after this, a right-sided vertebral-to-carotid artery anastomosis was
      performed during cardiopulmonary bypass (CPB)-induced deep hypothermia for
      optimal neuronal protection, with good results. However, early thrombosis of the
      right vertebral artery requiring reintervention in normothermia, without any
      stroke, indicate that deep hypothermia was unnecessary in this case, probably
      because of the previous natural and surgical development of collateral
      circulation. However, there was no means of predicting this in a reliable manner
      before the procedure and deep hypothermia appeared a safe technique for neuronal
      protection without any specific postoperative complications.

PMID- 10901541
TI  - Revascularization of femoropopliteal artery occlusion in Werner's syndrome.
      Report of a case and review of surgical literature in cardiovascular lesions.
AB  - A patient with Werner's syndrome suffering from a chronic ulcer on the right
      ankle joint underwent femoropopliteal bypass and patch angioplasty combined with
      endarterectomy of the distal popliteal artery. Postoperative angiography showed
      satisfactory graft patency and distal run-off, and the ulcer improved.
      Femoropopliteal occlusive disease in Werner's syndrome tends to have poor run-off
      and the internal diameter of the popliteal artery with diffuse arteriosclerotic
      lesion is often too small to facilitate distal anastomosis. Therefore, a
      conventional bypass procedure is not always effective and an aggressive attitude
      is essential to obtain sufficient ankle blood pressure and improve the leg ulcer
      in Werner' syndrome.

PMID- 10901542
TI  - Superior mesenteric vein thrombosis due to diverticulitis and spontaneous
      thrombolysis after ilio-cecal resection. A case report.
AB  - Inflammation or infection is one of the major causes of superior mesenteric vein
      thrombosis. A case of secondary superior mesenteric vein thrombosis is presented,
      which was identified with enhanced CT. The mesenteric venous thrombosis was due
      to diverticulitis of the ileum, and ilio-cecal resection was performed. Because
      no findings of intestinal ischemia were present, thrombectomy was not attempted.
      After surgery, the patient was followed up by repeated CT scan, and spontaneous
      thrombolysis without thrombectomy or thrombolytic therapy was exhibited. The
      present case indicated abdominal inflammation or infection strongly related to
      the development and regression of mesenteric venous thrombosis.

PMID- 10901543
TI  - Management of infected peripheral bypass by selective partial graft removal and
      arterial homograft insertion. Two case reports.
AB  - We present two cases of partial graft removal and cryopreserved arterial
      homograft insertion for treatment of patent axillobifemoral (AXB)
      polytetrafluoroethylene (PTFE) prosthesis with infection confined only to a part
      of the graft. In the first patient, infection was confined to the left inguinal
      site; in the second, there was a cutaneous fistula in the middle prosthetic
      thoracic tract. Neither patient presented signs of systemic sepsis and radio
      immunological tests were positive only in a confined tract. After surgery, both
      patients showed early recovery and currently (mean follow-up 21-month) they are
      disease-free. Selective partial graft removal appears to give satisfactory
      results and may reduce the risk of complications compared with total graft
      removal Moreover, arterial homograft shows greater resistance to infection
      compared to alloplastic materials, when autologous veins are not available and/or
      not suitable.

PMID- 10901544
TI  - Implantation of a composite bifurcated cryopreserved aorto-iliac-femoral
      homograft in a patient with Candida albicans endocarditis.
AB  - A 35 year old woman, cocaine addict, suffered Candida albicans aortic valve
      endocarditis complicated with embolisation of infected vegetations in the distal
      abdominal aorta. She underwent successful staged aortic valve replacement
      followed by transaortic and transfemoral thrombectomy. One month later an
      arteriogram disclosed partial occlusion of the left iliac artery, bilateral
      aneurysmal degeneration of both iliac arteries and right iliac artery-right iliac
      vein fistula. She was operated again, performing re-laparotomy and re
      exploration. A composite bifurcated cryopreserved homograft was implanted end-to
      side between the infrarenal abdominal aorta, right external iliac artery and left
      common femoral artery. The right iliac artery-iliac vein fistula was obliterated
      with suture. The patient had an uneventful recovery but a relapsing arterio
      venous fistula was diagnosed by arteriography. Three months later she underwent
      percutaneous transluminal closure of the reopened fistula. At present, 17 months
      after the implantation of the homograft, the patient is symptom-free, on
      antifungal agents and with arteriographic and clinical evidence of a well
      functioning arterial homograft.

PMID- 10901545
TI  - Aneurysm of a jejunal branch of the superior mesenteric artery in a patient with
      Marfan's syndrome.
AB  - A case of post-traumatic aneurysm of a jejunal branch of the superior mesenteric
      artery in a patient with Marfan's syndrome is reported. Ascending aortic
      involvement is well known in Marfan's syndrome but no association with visceral
      artery aneurysms has been previously described. The blunt abdominal trauma
      preceding the detection of the aneurysm may have been the precipitating cause in
      a predisposed patient. Because of the high risk of rupture, aneurysms of the
      superior mesenteric artery branches should be treated. Excision or ligation
      without restoring continuity are the most common surgical procedures;
      endovascular embolization is an alternative option especially in high risk
      patients.

PMID- 10901546
TI  - Primary aortosigmoid fistula treated by descending thoracic aortofemoral bypass.
AB  - Primary aortoenteric fistula is a rare disease with a fatal outcome unless it is
      diagnosed accurately and treated surgically. We present an elderly patient with
      primary aortosigmoid fistula confirmed by endoscopy. Descending thoracic
      aortofemoral bypass was performed and the aortoiliac aneurysm and sigmoid colon
      were then resected in continuity. The patient maintains a good quality of life 6
      years after the operation with good graft patency and no sign of graft infection.

PMID- 10901547
TI  - Familial dissecting aortic aneurysm in a mother and son.

PMID- 10901548
TI  - Aberrant origin of the left coronary artery.

PMID- 10901549
TI  - Partial circumflex artery injury during mitral valve replacement: late
      presentation.

PMID- 10901550
TI  - About self-hypnosis and coronary artery bypass surgery.

PMID- 10901551
TI  - Carbon monoxide poisoning in pregnancy.

PMID- 10901552
TI  - Prophylactic anticonvulsants for pre-eclampsia?

PMID- 10901553
TI  - Prevention of vaginal shortening following radical hysterectomy.
AB  - We describe a surgical procedure and post-operative management for the prevention
      of vaginal shortening following radical hysterectomy. A total of 452 patients who
      underwent hysterectomies were examined prospectively depending on the operation
      method. This study showed that our procedure was effective in the prevention of
      vaginal shortening following radical hysterectomy. Preservation of the ovaries
      appeared to be important in preventing vaginal shortening, and post-operative
      hormone replacement therapy was not as effective as the preservation of the
      ovaries. The effect of external irradiation on vaginal shortening was not
      conspicuous in the case that the ovaries were preserved.

PMID- 10901554
TI  - Standards for the management of cervical and vulval carcinoma.
AB  - OBJECTIVE: To examine the feasibility of achieving designated target standards
      for the management of women with cervical and vulval cancer. DESIGN:
      Retrospective casenote review. SETTING: The Gynaecological Oncology Centre at
      Hammersmith Hospital, London. POPULATION: Sixty-one women with cervical and
      vulval cancer presenting to the gynaecological oncology clinic at the Hammersmith
      Hospital during 1996 and 1997. Various aspects of the management of those women
      were compared with standards suggested by a multidisciplinary panel of local
      experts. Targets included the referral and treatment process, the accuracy of
      staging, and measures of surgical performance. RESULT: The target interval of
      seven days between receipt of the referral and the first visit at the cancer
      centre was achieved in 93% of women. Surgical treatment was administered to 92%
      of the women within the target of 20 working days from the first clinic
      appointment. Tumour close to or involving the margins of the specimen was noted
      in 13% of cervical and 9% of vulval cancers. The node count fell below the target
      standards in 13% of pelvic and 10% of groin dissections. Appropriate imaging
      investigations for staging were not undertaken in 15 of 39 cases (38%) of
      cervical cancer and in 5 out of 22 (23%) of vulval cancers. CONCLUSION: The
      suggested targets of process and surgical performance are reasonable and
      achievable. These standards would be appropriate for national use. The area most
      clearly identified where these targets were not achieved was the requesting of
      complementary staging investigations. This could be addressed by the use of a
      simple investigation protocol to be included in each patient's notes and
      available at specialist clinics and gynaecology wards.

PMID- 10901555
TI  - p53 and WAF1 polymorphisms in Jewish-Israeli women with epithelial ovarian cancer
      and its association with BRCA mutations.
AB  - OBJECTIVE: To investigate whether polymorphic p53 and WAF1 alleles are associated
      with clinical, demographic and histopathological features and BRCA mutation in
      women with ovarian cancer. DESIGN: A cross-sectional study. POPULATION: Two
      hundred and twenty-one nonselected Israeli women with epithelial ovarian cancer.
      METHODS: DNA was analysed for known polymorphisms in intron 3 (a 16 nucleotide
      single repeat) and intron 6 (a G to A change at nucleotide 13,494) of the p53
      gene, the S31R polymorphism in the WAF1 gene, and for three predominant Jewish
      mutations in the BRCA genes (185delAG and 5382insC in BRCA1, and 6174delT in
      BRCA2). MAIN OUTCOME MEASURE: The rate of polymorphic p53 and WAF1 alleles and
      their association with BRCA mutation, ethnic origin, age and stage at diagnosis,
      and family history of cancer. RESULTS: Of the tested women, 72 (32.6%) were
      either BRCA1 (n = 57) or BRCA2 (n = 15) mutation carriers. Sixty-eight of 213
      (31.9%) were heterozygous for intron 3 polymorphism, 67/193 (34.7%) for intron 6
      polymorphism, and 22/154 (14.3%) for S31R of the WAF1 gene. The p53 and WAF1
      polymorphism rate did not differ between BRCA mutation carriers and noncarriers.
      No significant association between specific p53 or WAF1 genotypes, and clinical,
      histopathological or demographic variables was observed. CONCLUSION: In Jewish
      Israeli women with sporadic and familial ovarian cancer, p53 or WAF1
      polymorphisms do not seem to affect the phenotype.

PMID- 10901556
TI  - The impact of adhesions on hospital readmissions over ten years after 8849 open
      gynaecological operations: an assessment from the Surgical and Clinical Adhesions
      Research Study.
AB  - OBJECTIVE: To investigate the epidemiology of, and the clinical burden related
      to, adhesions following gynaecological surgery. POPULATION: The Scottish National
      Health Service Medical Record Linkage Database was used to define a cohort of
      8849 women undergoing open gynaecological surgery in 1986. METHODS: All
      readmissions for potential adhesion related disease in the subsequent 10 years
      were reviewed. MAIN OUTCOME MEASURES: Readmissions and the degree of adhesion
      involvement gave an indication of clinical burden and workload. The rate of
      readmission following the initial surgery determined the relative risk of disease
      related to adhesions. RESULTS: Two hundred and forty-five (4.5%) of 5433
      readmissions following open gynaecological surgery were directly related to
      adhesions. 34.5% of patients were readmitted, on average 1.9 times, for a problem
      potentially related to adhesions or for further intra-abdominal surgery that
      could be complicated by adhesions. Readmissions related to adhesions continued
      throughout the 10 year period of the study. The overall rate of readmission was
      64.0/100 initial operations. For readmissions directly related to adhesions, the
      rate was 2.9/100 initial operations. Operations on the ovary had the highest rate
      directly related to adhesions (7.5/100 initial operations), with an overall rate
      of readmission of 106.4/100 initial operations. CONCLUSIONS: Despite the
      conservative approach taken in this study, the clinical burden, workload and
      relative risk of readmissions related to adhesions following open gynaecological
      surgery was considerable. Post-operative adhesions have important consequences
      for patients, surgeons and the healthcare system. These results emphasise the
      need for more effective strategies to prevent adhesions.

PMID- 10901557
TI  - A prospective study on the effects of depot medroxyprogesterone acetate on
      trabecular and cortical bone after attainment of peak bone mass.
AB  - OBJECTIVE: To study the annual change of bone mass in women aged 30-45 years
      being treated with depot medroxyprogesterone acetate (DMPA) in order to evaluate
      whether the bone mass depends on the duration of DMPA use or the oestradiol
      level. DESIGN: Prospective longitudinal study over an interval of 12 months.
      SETTING: A family planning centre of a university hospital. PATIENTS: Thirty-six
      current users of DMPA. INTERVENTIONS: Injection of 150 mg DMPA every 12 weeks.
      MEASUREMENTS: Bone mass was measured at the distal radius by peripheral
      quantitative computed tomography (reproducibility 0.3%). RESULTS: Mean annual
      changes (SD) in trabecular and cortical bone mass were 0.06 (1.6%) [P = 0.8] and 
      0.26% (0.6) [P < 0.04]. The decrease in cortical bone mass was not significant
      because the changes were within the precision error of the method used for the
      measurements. Duration of DMPA use and oestradiol levels were not associated to
      the bone parameters. CONCLUSION: We did not find a negative impact of DMPA on the
      bone mass of premenopausal women aged 30-45 years.

PMID- 10901558
TI  - A pilot study of Hypericum perforatum for the treatment of premenstrual syndrome.
AB  - OBJECTIVE: To investigate whether Hypericum perforatum could relieve symptoms of
      premenstrual syndrome in a small group of women in order to establish a
      hypothesis and to test methods for conducting a future randomised controlled
      trial. DESIGN: Prospective, open, uncontrolled, observational study. SETTING:
      Department of Complementary Medicine, University of Exeter. POPULATION: Nineteen
      women with premenstrual syndrome who were in otherwise good physical and mental
      health and not taking other treatments for premenstrual syndrome. METHOD:
      Volunteers underwent a preliminary screening interview, completed Daily Symptom
      Ratings for one cycle, and attended a medical screening visit before being
      diagnosed with premenstrual syndrome. Participants took hypericum tablets for two
      complete menstrual cycles (1 x 300 mg hypericum extract per day standardised to
      900 microg hypericin). MAIN OUTCOME MEASURES: Symptoms were rated daily
      throughout the trial using a validated measure. The Hospital Anxiety and
      Depression scale and modified Social Adjustment Scale were administered at
      baseline and after one and two cycles of treatment. RESULTS: There were
      significant reductions in all outcome measures. The degree of improvement in
      overall premenstrual syndrome scores between baseline and the end of the trial
      was 51%, with over two-thirds of the sample demonstrating at least a 50% decrease
      in symptom severity. Tolerance and compliance with the treatment were
      encouraging. CONCLUSION: The results of this pilot study suggest that there is
      scope for conducting a randomised, placebo-controlled, double-blind trial to
      investigate the value of hypericum as a treatment for premenstrual syndrome.

PMID- 10901559
TI  - The relationships between antenatal management, the cause of delivery and
      neonatal outcome in a large cohort of very preterm singleton infants.
AB  - OBJECTIVE: To determine whether the cause of very preterm delivery influences
      neonatal outcome. DESIGN: A cohort study of 685 consecutive singletons born
      before 33 weeks of gestation. METHODS: Causes of birth and perinatal outcome
      variables were correlated for statistical significance by uni- and multi-variate
      analyses. RESULTS: Intrauterine growth retardation or pre-eclampsia were
      associated with a higher rate of respiratory distress syndrome compared with
      prolonged rupture of membranes, after controlling for gestational age, antenatal
      corticosteroid therapy, antenatal antibiotic administration, mode of delivery and
      origin (inborn or outborn) (adjusted OR 3.12; 95% CI 1.55-6.28). The prevalence
      of grade 3-4 intraventricular haemorrhage or cystic periventricular leukomalacia
      was 25% in newborn babies born after intrauterine infection or prolonged rupture
      of membranes. Among infants born after intrauterine growth retardation/pre
      eclampsia, the rate of severe intraventricular haemorrhage was 3.2% and the rate
      of periventricular leukomalacia was 0.9%. Compared with intrauterine infection
      and after controlling for potential confounding covariates, intrauterine growth
      retardation/pre-eclampsia was associated with a lower rate of periventricular
      leukomalacia (adjusted OR 0.08; 95% CI 0.02-0.41). In the same multiple logistic
      regression model, antenatal corticosteroid administration was associated with a
      lower incidence of periventricular leukomalacia (adjusted OR 0.36; 95% CI 0.16
      0.79). CONCLUSIONS: The cause of very preterm delivery has an important influence
      on neonatal outcome.

PMID- 10901560
TI  - Dietary folate and the prevalence of neural tube defects in the British Isles:
      the past two decades.
AB  - OBJECTIVES: To measure the changes in folate consumption and the prevalence of
      neural tube defects in the British and Irish populations during the past two
      decades. DESIGN: Ecological study. MAIN OUTCOME MEASURES: Average daily dietary
      folate consumption for Britain for the period 1980-1996 was estimated from the
      National Food Survey. Annual neural tube defect prevalences for the same period
      were obtained from the Oxford Record Linkage Study Neural Tube Defect register,
      the Glasgow EUROCAT register, and the three Irish EUROCAT registers (Belfast,
      Dublin and Galway). RESULTS: Dietary folate consumption increased on average by
      1.6% per annum in Scotland and 1.4% in England during the study period. The
      annual rate of decline of neural tube defect prevalence averaged 10.4% in the
      Irish population, 8.2% in Glasgow, and 5.2% in Oxfordshire and West Berkshire.
      CONCLUSIONS: The decline in neural tube defect prevalence observed in all British
      and Irish populations since the early 1970s continued with the introduction of
      folate fortification of cereals, which produced measurable increases in average
      daily folate consumption. Further declines in neural tube defect prevalence may
      be achieved by targeted folate supplementation during the periconceptual period.

PMID- 10901561
TI  - Diet in late pregnancy and glucose-insulin metabolism of the offspring 40 years
      later.
AB  - OBJECTIVE: To determine how diets of women in pregnancy influence the glucose
      insulin metabolism of their offspring in adult life. DESIGN: A follow up study of
      men and women born during 1948-1954 whose mothers had taken part in a survey of
      diet in late pregnancy. SETTING: Aberdeen, Scotland. POPULATION: One hundred and
      sixty-eight men and women born in the Aberdeen Maternity Hospital. MAIN OUTCOME
      MEASURE: Plasma glucose and insulin concentrations, fasting and after a standard
      oral glucose challenge. RESULTS: The offspring of women who had high intakes of
      fat and protein in late pregnancy had a reduced plasma insulin increment between
      fasting and 30 min with a 7.0% decrease in increment (P = 0.007) per 10 g
      increase in protein intake and a 4.9% decrease (P = 0.002) per 10 g increase in
      fat intake. This was independent of the mother's body mass index or weight gain
      in pregnancy. A low maternal body mass index in early or late pregnancy was
      associated with a raised fasting plasma insulin concentration with a decrease of
      2.4% (P = 0.05) per 1 kg/m2 increase of maternal body mass. CONCLUSION: High
      intakes of protein and fat during pregnancy may impair development of the fetal
      pancreatic beta cells and lead to insulin deficiency in the offspring. The
      offspring of thin mothers tend to be insulin resistant.

PMID- 10901562
TI  - Epilepsy and pregnancy: effect of antiepileptic drugs and lifestyle on
      birthweight.
AB  - OBJECTIVE: To investigate the impact of epilepsy and antiepileptic drugs on
      length of gestation and anthropometric measures of the newborn. DESIGN: Cohort
      study based on questionnaires mailed to all pregnant women who attended for
      prenatal care at our department from August 1989 to January 1997. SETTING:
      Department of Obstetrics and Gynaecology at Aarhus University Hospital, Denmark.
      PARTICIPANTS: One hundred and ninety-three singleton pregnancies in women with
      epilepsy were compared with 24,094 singleton pregnancies in women without
      epilepsy. MAIN OUTCOME MEASURES: Preterm delivery, small for gestational age,
      mean gestational age, gestational age-adjusted birthweight, head circumference,
      and body length. RESULTS: Children of women with epilepsy who smoked had lower
      gestational age and were at increased risk of preterm delivery (OR 3.4; 95% CI
      1.8-6.5), compared with children born by nonepileptic women who smoked.
      Birthweight adjusted for gestational age was reduced by 102 g (95% CI 40-164) in
      women with epilepsy, and the risk of delivering a child who was small for
      gestational age was increased (adjusted OR 1.9, 95% CI 1.3-2.7), compared with
      women without epilepsy. Newborn babies of women with epilepsy treated by drugs
      had a reduced adjusted birthweight (208 g, 95% CI 116-300), head circumference
      (0.4 cm, 95% CI 0.0-0.7), and body length (0.5 cm, 95% CI 0.1-1.0), compared with
      the newborn infants of women without epilepsy. CONCLUSIONS: Women with epilepsy
      who smoked were at increased risk of preterm delivery compared with healthy
      smokers. Children of women with drug treated epilepsy had lower birthweight,
      length, and head circumference than children of women without epilepsy.

PMID- 10901564
TI  - A randomised controlled trial and meta-analysis of active management of labour.
AB  - OBJECTIVE: To test whether a policy of active management of nulliparous labour
      would reduce the rate of caesarean section and prolonged labour without
      influencing maternal satisfaction. DESIGN: Randomised controlled trial. SETTING:
      Tertiary referral obstetric unit, Auckland, New Zealand. POPULATION: Nulliparous
      women in spontaneous labour at term with singleton pregnancy and cephalic
      presentation and without fetal distress. METHODS: After the onset of active
      labour, previously consented women were randomly assigned to active management (n
      = 320) or to routine care (n = 331). Active labour was defined as regular painful
      contractions, occurring at least once in five minutes, lasting at least 40
      seconds, accompanied by either spontaneous rupture of the membranes, or full
      cervical effacement and dilatation of at least two centimetres. Active management
      included early amniotomy, two-hourly vaginal assessments, and early use of high
      dose oxytocin for slow progress in labour. Routine care was not prespecified.
      Prolonged labour was > 12 hours duration. Maternal satisfaction with labour care
      was assessed by postal questionnaire at six weeks postpartum. MAIN OUTCOME
      MEASURES: Mode of delivery, duration of labour, and maternal satisfaction.
      RESULTS: Active management of labour did not reduce the rate of caesarean section
      30/320 (9.4%), compared with 32/331 (9.7%) for routine care, but did shorten the
      length of first stage of labour (median 240 min vs 290 min; P = 0.02), and reduce
      the relative risk of prolonged labour (RR 0.39; 95% CI 0.22, 0.71). There were no
      differences between groups in the rates of newborn nursery admission, neonatal
      acidosis, low Apgar scores, or postpartum haemorrhage. Satisfaction with labour
      care was high (77%) and did not differ between groups. CONCLUSIONS: Active
      management of labour reduced the duration of the first stage of labour without
      affecting the rate of caesarean section, maternal satisfaction, or other maternal
      or newborn morbidity.

PMID- 10901563
TI  - Is the prophylactic administration of magnesium sulphate in women with pre
      eclampsia indicated prior to labour?
AB  - OBJECTIVE: To determine whether prophylactic magnesium sulphate is necessary to
      prevent eclampsia and associated complications among women with pre-eclampsia
      prior to labour. DESIGN: Case series. SETTING: Tertiary referral centre.
      POPULATION: Three hundred and eighteen women with pre-eclampsia (blood pressure >
      or = 140/90 mmHg and > or = 2+ proteinuria) who were not in labour or for planned
      induction thereof and had not received magnesium sulphate during transfer.
      METHODS: Clinical evaluation of the pregnant women with careful blood pressure
      control. Magnesium sulphate was withheld even in the presence of imminent
      eclampsia. During labour, the option of magnesium sulphate prophylaxis was left
      to the clinician, but magnesium sulphate was administered in cases of eclampsia.
      MAIN OUTCOME MEASURES: Eclampsia and related complications. RESULTS: Five women
      (1.5%) developed eclampsia, although none developed related complications. Women
      presented at an early gestational age (mean 30 weeks), with high blood pressure,
      often suffering from headaches. Twenty pregnancies were terminated prior to
      viability, of which half were terminated for maternal reasons. Ten intrauterine
      deaths occurred. Most often fetal distress (38.6%) initiated the delivery
      process, which was mainly by caesarean section (68.5%). With the exception of
      epigastric discomfort, symptoms and signs of imminent eclampsia decreased after
      admission. Blood pressure values were significantly lower at delivery although
      biochemistry results deteriorated from admission to delivery. CONCLUSION: In
      women with pre-eclampsia prior to labour, where blood pressure control was
      carefully applied but magnesium sulphate not given, the eclampsia rate was low
      and eclampsia did not appear to worsen the existing prognosis for mother or
      fetus.

PMID- 10901565
TI  - Umbilical artery Doppler studies in small for gestational age babies reflect
      disease severity.
AB  - OBJECTIVES: To determine: 1. whether abnormal umbilical artery Doppler studies
      were independently associated with newborn morbidity; and 2. whether small for
      gestational age babies with normal umbilical artery Doppler studies had small
      mothers and a low rate of newborn malnutrition and morbidity. DESIGN: Prospective
      observational study. SETTING: National Women's Hospital, a tertiary referral
      centre, Auckland, New Zealand. POPULATION: One hundred eighty-six women and their
      small for gestational age babies (birthweight < 10th%) who had been participants
      in one of two randomised controlled trials of small for gestational age
      pregnancies between 1993 and 1997. METHODS: Newborn morbidity and morphometry
      were compared between small for gestational age babies with normal and abnormal
      umbilical artery Doppler studies (resistance index > 95th%). Maternal demographic
      characteristics and morbidity were also compared. RESULTS: Compared with small
      for gestational age babies with normal umbilical artery Doppler studies (n =
      109), small for gestational age babies with abnormal umbilical artery Doppler
      studies (n = 77) were diagnosed earlier in pregnancy as being small for
      gestational age (30.3 vs 32.9 weeks, P < 0.001), were smaller in all body
      proportions at birth (median Z score birthweight -1.82 vs -1.70, P = 0.004, Z
      score length -1.86 vs -1.36, P < 0.0001, Z score head circumference -1.31 vs 
      0.89, P < 0.0001) and were more likely to experience newborn morbidity. When
      birthweight and gestation were entered into a logistic regression model, an
      abnormal umbilical artery Doppler study was not an independent predictor of
      prolonged newborn nursery admission or hypoglycaemia. Of small for gestational
      age babies with normal umbilical artery Doppler studies, 53 (49%) had low
      ponderal indices, 26/98 (26%) were hypoglycaemic and 38 (35%) required admission
      to the newborn nursery. There was no difference in maternal height, weight and
      ethnicity between the abnormal and normal umbilical artery Doppler groups.
      CONCLUSIONS: Abnormal umbilical artery Doppler studies reflect earlier onset and
      more severe growth restriction and are not independently associated with newborn
      morbidity. Small for gestational age babies with normal Doppler studies have a
      high rate of newborn nursery admission and malnutrition at birth and are not all
      just normal small babies.

PMID- 10901566
TI  - Anal sphincter tears: prospective study of obstetric risk factors.
AB  - OBJECTIVE: To evaluate intrapartum risk factors for anal sphincter tear. DESIGN:
      A prospective observational study. SETTING: Delivery unit at the University
      Hospital in Goteborg, Sweden. PARTICIPANTS: 2883 consecutive women delivered
      vaginally during the period between 1995 and 1997. Information was obtained, from
      patient records and from especially designed protocols which were completed
      during and after childbirth. MAIN OUTCOME MEASURES: Anal sphincter (third and
      fourth degree) tear. RESULTS: Anal sphincter tear occurred in 95 of 2883 women
      (3.3%). Univariate analysis demonstrated that the risk of anal sphincter tear was
      increased by nulliparity, high infant weight, lack of manual perineal protection,
      deficient visualisation of perineum, severe perineal oedema, long duration of
      delivery and especially protracted second phase and bear down, use of oxytocin,
      episiotomy, vacuum extraction and epidural anaesthesia. After analysis with
      stepwise logistic regression, reported as odds ratio, 95% confidence interval,
      the following factors remained independently associated with anal sphincter tear:
      slight perineal oedema (0.40, 0.26-0.64); manual perineal protection (0.49, 0.28
      0.86); short duration of bear down (0.47, 0.24-0.91); no visualisation of
      perineum (2.77, 1.36-5.63); parity (0.59, 0.40-0.89); and high infant weight
      (2.02, 1.30-3.16). Analysis of variance showed that manual perineal protection
      had a stronger influence on lowering the frequency, and lack of visualisation of
      perineum and infant weight had a stronger influence on raising the frequency, of
      anal sphincter tears in nulliparous compared with parous women. CONCLUSIONS:
      Perineal oedema, poor ocular surveillance of perineum, deficient perineal
      protection during delivery, protracted final phase of the second stage, parity
      and high infant weight all constitute independent risk factors for anal sphincter
      tear. Such information is essential in order to reduce perineal trauma during
      childbirth.

PMID- 10901567
TI  - Outcome of the next labour in women who had a vaginal delivery in their first
      pregnancy.
AB  - This study reviews the outcome of the next labour in women who are delivered
      vaginally in their first pregnancy. The influence of the method of delivery in
      the first pregnancy and of factors in both the first and next labour on the type
      of delivery in the second pregnancy, are recorded in a group of 13,813 women.
      Those delivered spontaneously and by vacuum, low forceps and mid-forceps in their
      first pregnancy had a 96%, 91%, 88% and 82% chance, respectively, of spontaneous
      delivery in their next pregnancy. The type of labour (spontaneous, induced or
      augmented) in the first pregnancy had minimal influence on the method of delivery
      in the second pregnancy. Compared with spontaneous onset, induction and
      augmentation of labour in the second pregnancy reduced the chance of spontaneous
      delivery by 6% and 18%, respectively.

PMID- 10901568
TI  - Elevated circulating homocyst(e)ine levels in placental vascular disease and
      associated pre-eclampsia.
AB  - We examined the hypothesis that hyperhomocyst(e)inaemia in the maternal or fetal
      circulation is associated with placental vascular disease with either the
      maternal syndrome of pre-eclampsia and/or fetal syndrome of growth restriction.
      Maternal plasma homocyst(e)ine levels were significantly higher in pregnancies
      complicated by pre-eclampsia, pregnancies with evidence of umbilical placental
      vascular disease, and pregnancies with both complications compared with the
      normal pregnancy group. In the fetal circulation mean plasma homocyst(e)ine
      concentration was significantly higher in the pre-eclampsia group compared with
      the normal group. The results suggest that hyperhomocyst(e)inaemia may be a risk
      marker for placental vascular disease and maternal pre-eclampsia. The elevated
      fetal plasma homocyst(e)ine concentrations, found only in the group of
      pregnancies with pre-eclampsia in the absence of umbilical placental vascular
      disease, may be due to an effect of placental vascular disease on homocyst(e)ine
      transfer from the maternal to fetal circulation.

PMID- 10901569
TI  - Acute postpartum myocardial infarction after ergometrine administration in a
      woman with familial hypercholesterolaemia.

PMID- 10901570
TI  - An inborn error of metabolism imitating hypoxic-ischaemic encephalopathy.

PMID- 10901571
TI  - An emerging trend in anti-reflux surgery?

PMID- 10901572
TI  - Percutaneous endoscopic laser discectomy.
AB  - BACKGROUND: The aim of the present paper was to systematically review the
      literature on percutaneous endoscopic laser discectomy (PELD) with respect to the
      safety and efficacy of the procedure. Where possible the procedure was compared
      with open discectomy. METHODS: Studies on PELD were identified using MEDLINE
      (1984 to December 1999), EMBASE (1974 to December 1999) and Current Contents
      (1993 to Week 1, 2000). A number of search terms were used: PELD; PLDD
      (percutaneous laser disc decompression); and laser and (spine or lumbar) and
      (disc* or disk*). The Cochrane Library was searched from 1966 to issue 4, 1999,
      using the search terms 'discectomy' or 'discotomy'. Live human studies of
      patients with lumbar disc prolapses for whom surgery was appropriate were
      included. Cadaver studies were also included. A surgeon and reviewer
      independently assessed the retrieved articles for their inclusion in the review.
      RESULTS: Only 12 papers were identified that related to PELD. The level of
      evidence for safety and efficacy was low; there were no controlled, blinded or
      randomized studies. The highest level of evidence came from time series studies.
      No quantitative analysis could be undertaken for the present review. CONCLUSIONS:
      Given the extremely low level of evidence available for this procedure it was
      recommended that the procedure be regarded as experimental until results are
      available from a controlled clinical trial, ideally with random allocation to an
      intervention and control group.

PMID- 10901573
TI  - Contamination of banked femoral head allograft: incidence, bacteriology and donor
      follow up.
AB  - BACKGROUND: Allograft donations are not uncommonly found to be contaminated. The
      issue of contaminated donations from live donors at the time of surgery, and the
      significance of this to the patient in terms of subsequent sepsis of the
      arthroplasty, were examined. METHODS: The donations of femoral heads to the
      Queensland Bone Bank over a 9-year period were reviewed, and the incidence and
      bacteriology of contamination were detailed. Clinical outcomes were determined
      for donors who had positive cultures at the time of retrieval and they were
      compared with those of culture-negative donors. RESULTS: Between March 1987 and
      February 1996, 232 femoral heads were donated to the Queensland Bone Bank. Four
      specimens were sent for culture with each femoral head (surface swab of femoral
      head, acetabular swab, bone biopsy and capsule). In 51 cases, one or more
      positive cultures were obtained (22% contamination rate). The majority of
      organisms cultured were Staphylococcus epidermidis. One hundred and seventy
      donations came from surgery performed at the Princess Alexandra Hospital, and 40
      femoral heads were considered contaminated. Deep infection was recorded in one of
      the 40 cases with contaminated donations and three out of 130 non-contaminated
      donations had subsequent septic episodes. CONCLUSION: The contamination rate
      detailed in the present report is higher than in most series. This may be due to
      the fact that four bacteriological specimens are taken to assess contamination.
      Two of these specimens are tissue samples which yielded more positive results
      than did the two swabs. All other series take no more than two bacteriological
      specimens, which are usually bone swabs. These are shown to have a poor yield of
      positive cultures. Therefore there is a significant underestimation of
      contamination rates by other bone banks. This has implications for the recipients
      of bone from those banks, particularly when the allograft material is not
      secondarily sterilized. This is important given increasing allograft usage, and
      the increasing numbers of revision joint arthroplasty and impaction grafting
      procedures being performed. Sterilization of all bone by irradiation to 25 kGy is
      recommended.

PMID- 10901574
TI  - Clinical and histological factors associated with sentinel node identification in
      breast cancer.
AB  - BACKGROUND: Although sentinel lymph node biopsy is likely to be offered as a
      method of assessing nodal status in primary breast cancer, the inability to
      identify the sentinel node at the time of surgery will limit the number of
      patients who may benefit from the procedure. The purpose of the present study was
      to identify factors that are associated with intraoperative identification of the
      sentinel node(s). METHODS: Between September 1995 and May 1999, lymphatic mapping
      using a combination of preoperative lymphoscintigraphy and/or blue dye was
      performed on 169 consecutive patients with clinically lymph node-negative primary
      operable breast cancer. Clinical and histological factors were assessed using
      univariate and multivariate analysis to determine those that were associated with
      intraoperative identification of the sentinel node. RESULTS: The sentinel node
      was identified at the time of surgery in 142 cases (84%). Of the clinical factors
      assessed, preoperative identification of the sentinel node on lymphoscintigraphy
      (P < 0.0001), use of blue dye in combination with isotope (P = 0.001),
      symptomatic palpable tumours (P < 0.05) and the experience of the surgeon (P =
      0.03) were significant in identifying the sentinel node at operation. No
      histological factor was associated with intraoperative identification of the
      sentinel node. Using multivariate analysis, positive identification of the
      sentinel node on lymphoscintigram, the experience of the surgeon and the use of
      both blue dye and isotope for sentinel node mapping were independent factors
      associated with intraoperative sentinel node identification. The lymphoscintigram
      result was the strongest independent factor according to its beta value, a
      measure of the weight of significance. CONCLUSION: Patients undergoing sentinel
      lymph node mapping and biopsy should be warned of the possibility of failure of
      sentinel node identification at operation. Our results suggest that the best
      predictor of intraoperative sentinel node identification is the visualization of
      the sentinel node on preoperative lymphoscintigraphy. The result of the
      lymhoscintigram may allow for additional preoperative counselling of the patient
      regarding the success or failure of sentinel node biopsy. Technical factors such
      as the experience and diligence of the surgeon, as well as the sentinel node
      mapping technique, are also important in determining the success of the
      procedure.

PMID- 10901575
TI  - Thyroid surgery and anaesthesia following head and neck irradiation for childhood
      malignancy.
AB  - BACKGROUND: Increasing numbers of adolescents and young adults are undergoing
      thyroid surgery because of the risk of malignancy following previous irradiation
      for childhood malignancy. Irradiation to the head and/or neck regions may induce
      changes in the soft tissues and larynx that are far from normal with respect to
      both size and mobility. The aim of the present study was to evaluate the possible
      impact of such changes on both surgical and anaesthetic technique during
      thyroidectomy. METHODS: This was a retrospective ease study. Thirty consecutive
      patients undergoing total thyroidectomy following previous irradiation for
      childhood malignancy formed the study group. RESULTS: There were no permanent
      surgical or anaesthetic complications in the group. In particular there were no
      cases of either permanent recurrent laryngeal nerve palsy or permanent
      hypoparathyroidism. Twenty-eight patients had an uneventful intubation and two
      were unable to be intubated directly, one requiring fibre-optic bronchoscopic
      intubation and the other having surgery performed with a laryngeal mask following
      failed bronchoscopy. Both of these patients had received high-dose direct
      irradiation to the larynx for solid tumours. CONCLUSIONS: Despite potential
      difficulties associated with the heavily irradiated larynx, thyroid surgery and
      anaesthesia can be performed safely with minimal complications in experienced
      hands.

PMID- 10901576
TI  - Liver transplantation in patients with transjugular intrahepatic portosystemic
      shunts.
AB  - BACKGROUND: In patients with intractable oesophageal variceal bleeding,
      transjugular intrahepatic portosystemic shunts (TIPSS) are being used
      increasingly as a bridge to orthotopic liver transplantation (OLTx). There is
      little information in the literature concerning variations in the operative
      techniques of OLTx required because of the presence of TIPSS. METHODS: A
      retrospective review of patients treated by TIPSS prior to OLTx was undertaken.
      The aims were to assess the effectiveness of TIPSS in bridging patients to OLTx
      and to examine whether TIPSS influence the operative management of OLTx. RESULTS:
      Over a 4-year period eight adult patients underwent TIPSS insertion prior to OLTx
      in the Australian National Liver Transplant Unit (ANLTU). Transplantation was
      performed at a mean of 14.6 (0.3-53.8) months after TIPSS insertion. Prevention
      of major recurrent variceal haemorrhage prior to transplantation was achieved in
      six cases. In two patients the stents were predominantly intrahepatic and they
      did not interfere with OLTx. In five patients the stents extended into the portal
      vein, requiring removal during OLTx either by division of the stent with the
      recipient portal vein, followed by removal of the fractured stent wires from the
      portal veins (n = 3), or by 'endarterectomy' of the recipient portal vein,
      allowing removal of the intact stent (n = 2). In one case where the stent
      extended into the suprahepatic inferior vena cava, removal was achieved by
      traction without difficulty. All patients are alive at a mean of 24 (7-53) months
      post-transplant and none has portal vein abnormalities. When compared to 178
      adult patients who had no TIPSS and underwent primary OLTx during the same study
      period, there was no difference in the length of operating time or the usage of
      blood products during OLTx. CONCLUSION: Transjugular intrahepatic portosystemic
      shunts offer a bridge to OLTx by providing effective control of variceal
      haemorrhage. In the present series TIPSS did not increase surgical morbidity or
      mortality, but emphasis is placed upon the need for optimal TIPSS placement
      within the liver to facilitate subsequent OLTx.

PMID- 10901577
TI  - Hepatic artery access ports: recognizing and avoiding the problems.
AB  - BACKGROUND: Regional approaches to the management of hepatic tumours are
      appropriate in some clinical situations and include hepatic arterial chemotherapy
      (HAC) and selective internal radiation therapy (SIRT). Both require access to the
      hepatic artery, which is conveniently achieved with a subcutaneously placed port.
      Placement and use of these ports may be associated with a variety of technical
      problems which can impact adversely on the outcome of the treatment. The present
      paper outlines the problems related to port usage for regional hepatic therapies,
      with emphasis on the technical aspects of insertion and interpretation and
      management of subsequent problems. METHODS: Hepatic artery port placement was
      attempted in 129 patients for use with either SIRT and/or HAC. Ports were used or
      flushed at monthly intervals. RESULTS: Successful port insertion was achieved in
      127 patients, of whom 87 received HAC alone, seven received SIRT alone, 28
      patients received both and in five patients the port was never used. Methylene
      blue injection was used to identify anomalous arterial anatomy, which was found
      in 26 of 95 patients (27%), and significant extrahepatic 'access', which was seen
      in 25 patients (26%) after initial placement. Forty-six instances of technical
      problems preventing continued use of the port occurred in 43 patients after a
      median of 4 (0-36) cycles of chemotherapy, including hepatic artery thrombosis (n
      = 26), catheter blockage (n = 4), duodenal fistula (n = 3), gastrointestinal (GI)
      bleeding (n = 3), side-effects (n = 3), access problems (n = 3), extravasation (n
      = 3) and infection (n = 1). CONCLUSION: Methods used to identify, manage and in
      some instances prevent the occurrence of these problems are discussed.

PMID- 10901578
TI  - Selective vascular occlusion with staged hemihepatectomy for blunt liver trauma.
AB  - BACKGROUND: A 23-year-old man with extensive blunt trauma to the right lobe of
      the liver in whom adequate haemostasis could not be achieved by selective
      suturing and packing was encountered. Contributing factors to poor haemostasis
      included massive transfusion, hypothermia and acidosis. METHODS: Hepatic
      haemostasis was achieved by selective intrahepatic ligation of the right hepatic
      pedicle and packing. RESULTS: After resuscitation and stabilization in the
      intensive care unit, a right hemihepatectomy was performed 14 h later.
      CONCLUSIONS: The present case describes a modification of the Pringle manoeuvre,
      termed 'selective Pringle manoeuvre'. This technique is a useful additional
      strategy for the management of uncontrollable bleeding in massive hepatic trauma.

PMID- 10901579
TI  - Use of an ambulance-based helicopter retrieval service.
AB  - BACKGROUND: John Hunter Hospital is the major trauma centre for a region covering
      more than 25,000 square kilometres. The helicopter primary retrieval service for
      trauma is paramedic staffed and protocol driven. The aim of the present study was
      to assess the overtriage rate created by such protocols, and to assess the
      benefit to patient outcomes that may be attributable to the service. METHODS: The
      John Hunter Hospital trauma database was used to identify all cases arriving by
      helicopter in 1996, as well as their demographic details, injury severity score,
      details of the accident and outcome. An expert panel reviewed the medical records
      for the 184 primary retrievals. Using a consensus model, estimates of time delay
      or saving were calculated and likelihood of benefit, no benefit or harm was
      assessed. RESULTS: A total of 3087 trauma patients were assessed at John Hunter
      Hospital in 1996, of which 8% arrived by helicopter. Of the primary retrievals,
      67.6% had an injury severity score of 9 or less, with only 17.9% having a score
      of 16 or greater. Twelve patients were discharged from Emergency and 36% were
      discharged within 48 h. The overall mortality was 5.0%. Twenty-five per cent of
      patients were retrieved within 35 km of John Hunter Hospital with minimal
      attributable benefit. Overall 1.7% of patients were felt to have been potentially
      harmed, 17.3% to have benefited and 81.0% to have had no attributable benefit
      related to the helicopter use. CONCLUSIONS: Although the majority of retrievals
      are for minor injuries, the service provides benefit for the region. There is
      potential for harm, however, where base hospitals are overflown in situations
      where patients have airway compromise, and where patient transfer is delayed due
      to helicopter activation. Primary helicopter tasking to trauma cases within 35 km
      of the major trauma centre is seldom beneficial.

PMID- 10901580
TI  - Corpus cavernosum as an alternative means of intravenous access in the emergency
      setting.
AB  - BACKGROUND: The present study was designed to investigate the feasibility of
      using the corpus cavernosum as an alternative means of intravenous access in the
      emergency setting. METHODS: The feasibility of achieving the infusion flow rates
      was first ascertained using direct intracavernous infusion of normal saline. The
      effect of atropine and adrenaline when given via this route was then studied.
      Hypovolaemic shock was then induced in dogs who were then actively resuscitated
      via this route using normal saline, Haemaccel and whole blood. RESULTS: Infusion
      flow rates were achieved for normal saline of 32.3, 50.3 and 67.3 mL per min at
      100, 200 and 300 mmHg pressure, respectively. The peak effects of atropine and
      adrenaline via this route were seen at approximately 1 min after injection.
      Resuscitation using this method was uniformly successful in all dogs via the
      corpus cavernosum, with all reaching or exceeding their premorbid central venous
      pressure (CVP), and approaching or reaching their premorbid mean arterial
      pressure (MAP). In comparison the control dog's CVP and MAP did not rise during
      the period of observation after it was bled. CONCLUSIONS: The corpus cavernosum
      is a practical alternative means of intravenous access in the emergency setting
      in the dog model.

PMID- 10901581
TI  - Role of axillary surgery in early breast cancer: review of the current evidence.
AB  - BACKGROUND: Controversy continues to surround the best practice for management of
      the axilla in patients with early breast cancer (EBC), particularly the
      clinically negative axilla. The balance between therapeutic and staging roles of
      axillary surgery (with the consequent morbidity of the procedures utilized) has
      altered. This is due to the increasing frequency of women presenting with early
      stage disease, the more widespread utilization of adjuvant chemoendocrine therapy
      and, more recently, the advent of alternative staging procedures, principally
      sentinel node biopsy (SNB). The aim of the present review is to critically
      analyse the current literature concerning the preferred management of the axilla
      in early breast cancer and make evidence-based recommendations on current
      management. METHODS: A review was undertaken of the English language medical
      literature, using MEDLINE database software and cross-referencing major articles
      on the subject, focusing on the last 10 years. The following combinations of key
      words have been searched: breast neoplasms, axilla, axillary dissection,
      survival, prognosis, and sentinel node biopsy. RESULTS: Despite the trend to more
      frequent earlier stage diagnosis, levels I and II axillary dissection remain the
      treatment of choice in the majority of women with EBC and a clinically negative
      axilla. CONCLUSIONS: Sentinel node biopsy has no proven superiority over axillary
      dissection because no randomized controlled trials have been completed to date.
      Despite this, SNB will become increasingly utilized due to encouraging results
      from major centres responsible for its development, and patient demand. Therefore
      if patients are not being enrolled in clinical trials strict quality controls
      need to be established at a local level before SNB is allowed to replace standard
      treatment of the axilla. Unless this is strictly adhered to there is a
      significant risk of an increase in the frequency of axillary relapse and possible
      increased understaging and resultant inadequate treatment of patients.

PMID- 10901582
TI  - Laparoscopic intraperitoneal foreign body from adhesive drapes.
AB  - The present paper reports three cases where portions of adhesive drape were drawn
      into the peritoneal cavity during cannula insertion. If adhesive drapes are used
      it is recommended that generous skin incisions be made to avoid this
      complication.

PMID- 10901584
TI  - Reverse ball valve syndrome: retrograde intussusception of a duodenal polyp.

PMID- 10901583
TI  - Frederic Wood Jones: his illnesses.
AB  - As an inveterate sea traveller Wood Jones never conquered seasickness. An attack
      of appendix in 1910 is also described. Following another attack in 1913 his
      appendix was removed. Within 24 h of surgery he was laid low by gout. Gout struck
      again in 1949. There followed two papers on his disease. In 1920 he confessed
      that he had had 'lumbago' and sciatica for a long while. He was admitted to
      Westminster Hospital on 23 March 1954 and died in the same hospital on 29
      September of that year.

PMID- 10901585
TI  - Variation of palmaris longus tendon.

PMID- 10901586
TI  - Idiopathic megacolon causing iliac vein occlusion and hydronephrosis.

PMID- 10901587
TI  - Laparoscopy in the management of intestinal duplication in childhood.

PMID- 10901588
TI  - Erythropoietin and anemia of cancer.
AB  - Anemia is a common complication of cancer but its causes differ widely. However,
      a significant number of patients with even early cancer experience a suppression
      of the action of erythropoietin on the bone marrow, presumably caused by the
      release of cytokines. The ensuing anemia may be mild and "asymptomatic".
      Nevertheless, it drains physical and emotional vigor so necessary in the fight
      against the underlying disorder. The therapeutic use of recombinant human
      erythropoietin has been gratifying and in many cases restored to near normal not
      only the hemoglobin concentration but also the quality of life.

PMID- 10901589
TI  - Novel therapeutic targets in multiple myeloma.
AB  - Multiple myeloma remains an incurable disease, and a new perspective on the
      approach to therapy is required. The aim of this review is to focus on a number
      of key areas where recent advances in the biology of the disease have not only
      yielded an understanding of the disease pathogenesis but have also suggested
      novel treatment approaches. Factors mediating myeloma cell growth, survival and
      the complex interaction of myeloma cells with the bone marrow microenvironment
      have provided a framework for the rational design of therapeutic agents. The
      development of such biologically based treatments which target both the tumour
      cell and the microenvironment, in order to achieve more complete and selective
      eradication of myeloma cells and the maintenance of minimal residual disease
      states, may ultimately lead to improved disease-free survival and potentially a
      cure.

PMID- 10901590
TI  - Human immunodeficiency virus-associated malignant lymphoma in eastern Denmark
      diagnosed from 1990-1996: clinical features, histopathology, and association with
      Epstein-Barr virus and human herpesvirus-8.
AB  - The clinicopathological features of human immunodeficiency virus (HIV)-associated
      lymphoma were investigated in a retrospective study of 85 adult patients in
      eastern Denmark diagnosed during the period 1990-1996. The possible pathogenetic
      role of Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) in these tumours
      was also studied. Seventy patients (82%) presented with extranodal disease and 26
      (31%) had CNS involvement at diagnosis. Diffuse large cell B-cell lymphoma was
      the most frequent histological subtype, comprising 65 of 79 cases available for
      microscopic re-evaluation (82%) and including 20 of 23 evaluable patients with
      CNS lymphoma (87%). EBV RNA was demonstrated by in situ hybridization in 51 of 65
      evaluable tumours (79%) and in 14 of 16 cases (88%) with CNS-lymphoma. Three
      cases showed a T-cell phenotype. The presence of HHV-8 DNA was analysed by PCR in
      32 cases. A strong band consistent with tumour cell infection was detected in
      only one case, weaker bands being seen in 4 cases. None of these patients had
      primary effusion lymphomas. In conclusion, Danish AIDS-related lymphomas are of
      predominantly high-grade B-cell type with extranodal localization and atypical
      presentation. Our results provide further evidence that EBV plays a major role in
      the pathogenesis of large cell AIDS-related lymphoma, whereas HHV-8 does not
      appear to contribute significantly to the development of solid lymphomas in this
      group of patients.

PMID- 10901591
TI  - B-lymphocytes in CLL and NHL differ in the mRNA splicing pattern of the CD45
      molecule.
AB  - In the present study the cell surface expression of CD45 isoforms on normal and
      neoplastic human B cells was correlated with splice products of the CD45 mRNA,
      using RT-PCR technology. In non-Hodgkin's lymphoma cells in the leukemic phase
      (NHL) the majority of the cells expressed a high level of CD45RA, while in CLL
      most of the cells expressed a low level. In the Raji and Daudi Burkitt B-cell
      lymphoma lines the main CD45 mRNA product was the largest, unspliced, full-length
      isoform (456) and the 56 splice product. Similar results were obtained with B
      cell lymphoma cells isolated from the peripheral blood of patients with NHL in
      the leukemic phase. In EBV-transformed B-cell lines, the 456 and the 56 isoform
      of CD45 mRNA were predominant, but in addition a low level of the 5- and 0-exon
      splice products was detected. A strikingly different pattern was obtained with B
      CLL cells. In CLL the level of the 456 and the 56 isoforms was low, while that of
      the 5- and 0-exon splice products was increased. Thus, in contrast to the
      heterogeneity in the expression of CD45RO in B-CLL, the majority of the cells
      contained the CD45 mRNA splice product coding for CD45RO. Analysis of splice
      products of the CD45 mRNA may serve as an additional tool to differentiate CLL
      from the leukemic phase of NHL.

PMID- 10901592
TI  - Clonal patterns of X-chromosome inactivation in female patients with aplastic
      anaemia studies using a novel reverse transcription polymerase chain reaction
      method.
AB  - Conflicting results have been published on the frequency of clonal patterns of X
      chromosome inactivation in female patients with aplastic anaemia. Previous
      studies have used DNA methylation to measure X-inactivation, but aberrant
      methylation is known to occur in some situations. We have developed a non
      radioactive reverse transcription polymerase chain reaction (RT-PCR) method to
      study expression of the polymorphism at nt. 1311 of the G6PD gene at the RNA
      level. Using this, and a similar method for the iduronate-2-sulfatase (IDS) gene,
      we have re-evaluated X-inactivation in AA patients. 32/35 normal individuals
      showed polyclonal haemopoiesis. Patients with presumed clonal diseases showed
      both monoclonal and polyclonal patterns, consistent with previous reports.
      Overall, clonal patterns were observed in granulocytes of 10/26 AA patients
      (38%), a significantly higher proportion than in controls (p<0.01). Two cases
      showed discordance between lymphocytes and granulocytes, indicating clonality
      arising within the myeloid lineage. Eight cases showed clonal patterns in both
      myeloid and lymphoid cells, indicating the involvement of a pluripotent stem
      cell. Clonal patterns did not correlate with age, but there appeared to be an
      association with duration of disease. In PNH patients, CD59-negative cells showed
      clonal patterns of X-inactivation. In two cases, however, clonal patterns were
      also detected in CD59-positive cells.

PMID- 10901593
TI  - Relation of ferritin levels to pulmonary function in patients with thalassemia
      major and the acute effects of transfusion.
AB  - We studied 36 patients (17 males and 19 females) with thalassemia major by
      performing pulmonary function testing (PFT), arterial blood gas analysis (ABG),
      as well as determining the serum ferritin level. In addition, 19 of these
      patients were transfused with two units of packed cells, and a repeat ABG and PFT
      were performed. Twenty-three patients had normal PFTs, eleven patients (30.6%)
      showed a restrictive pattern (significant decrease in both TLC and DLCO), and
      only two patients (5.6%) showed an obstructive pattern. A significant negative
      correlation was found between serum ferritin and restrictive parameters, DLCO and
      TLC (p = 0.01 and p = 0.03, respectively). This correlation was even stronger
      after transfusion. Controlling for age, ferritin was still negatively correlated
      with DLCO (p = 0.04), but no longer with TLC. There was no correlation between
      age and DLCO or age and TLC; however, there was a statistically significant
      negative correlation between age and FVC (p = 0.003). Analysis of patients who
      were transfused revealed a significant decrease in forced vital capacity (89 +/-
      4% vs. 74 +/- 5% of predicted; p-value < 0.001) and in maximum midexpiratory flow
      rate (79 +/- 4% vs. 67 +/- 5% of predicted; p-value = 0.004). For patients older
      than 15 yr of age, there was a statistically significant decrease in FEV1/FVC (84
      +/- 2 vs. 83 +/- 2%; p-value = 0.04). The ABGs showed no significant change post
      transfusion. In this study, PFT findings in thalassemia major were restrictive
      and correlated with serum ferritin level. Transfusion had an acute effect on the
      obstructive parameters of PFT.

PMID- 10901594
TI  - Filtered platelet concentrates from pooled buffy coats show comparable storage
      lesions when stored for 9 d at 20-24 degrees C or when supplemented with
      thromboSol at 2-6 degrees C.
AB  - The present study investigated the quality of platelet concentrates from pooled
      buffy coat (PCBC) along different production steps and during storage to
      characterize storage lesions reflected by platelet activation, changing metabolic
      and cell turnover status (pH, LDH activity). These criteria were compared in
      conventionally stored PCBCs (20-24 degrees C, n = 8, Group I) to cold stored
      PCBCs (2-6 degrees C, n = 8, Group II) when supplemented with ThromboSol.
      Platelet activation was measured on days 1, 3, 7 and 9 by flow cytometry using
      fluoresceinisothiocyanate-labeled monoclonal antibodies (mAbs) against
      glycoprotein IIb/IIIa (CD41a, PAC-1 and LIBS-1), P-selectin (CD62P) or CD40
      ligand receptor (CD40L) in combination with a phycoerythrin-labeled panspecific
      platelet marker against GPIb (CD42b). The platelet activation assessed with mAbs
      PAC-1, CD41a, LIBS-1 and CD40L showed an overall activation of 98 +/- 4% (mean
      value +/- 1 SD) at day 7 in both groups, except for CD62P, which was
      significantly lower in Group II. A storage-dependent greater platelet loss
      occurred in Group II compared to Group I, 42% vs. 19% (p < 0.05 on day 9). We
      could demonstrate that platelets stored in ThromboSol show about the same in
      vitro activation as conventionally stored PCBCs, but their clinical usefulness
      needs to be investigated.

PMID- 10901595
TI  - Oral cyclic megadose methylprednisolone therapy for chronic immune
      thrombocytopenic purpura in childhood.
AB  - The objectives of this study were to investigate the effectiveness of oral
      megadose methylprednisolone (OMMP) therapy in children with chronic immune
      thrombocytopenic purpura (ITP). Twenty-two patients were given oral
      methylprednisolone daily for 7 d (30 mg/kg for 3 d and then 20 mg/kg for 4 d).
      OMMP therapy was repeated once per month if the platelet count was less than
      20,000/mm3 at the 30th day of therapy, for up to six courses. The number of
      platelets of all patients increased gradually during the OMMP therapy, with a
      peak number at the 7th day, then decreased until the 14th day, and remained
      relatively stable until 12 months. During the study no patient had a platelet
      count less than 20,000/mm3 at the 3rd day and 50,000/mm3 at the 7th day. Although
      the number of platelets was gradually decreased between the 7th and 14th days, it
      remained above 100,000/mm3 for at least 12 months in the nine patients, and above
      20,000/mm3 in the four patients. None of these 13 patients required
      hospitalization or therapy during the follow-up period. All of the patients
      tolerated the medication well. None of them reported side-effects that were
      severe enough to discontinue therapy. We conclude that OMMP therapy is a safe,
      easy and effective therapy in children with refractory chronic ITP, and it may
      provide long-term remission in about two thirds of the patients.

PMID- 10901596
TI  - Organ specificity of c-kit+ lymphoid precursors in the liver, thymus, and bone
      marrow.
AB  - c-kit+Lin- cells are present in various immune organs, including the liver,
      thymus, and bone marrow, where lymphoid, myeloid, or erythroid cells are
      generated. To compare their properties as lymphoid precursors, c-kit+Lin- cells
      purified from various organs of B6.Ly5.1 mice were injected into 6.5 Gy
      irradiated B6.Ly5.2 mice. Depending on the source of the c-kit cells, the degree
      of entrance and expansion of lymphoid cells differed in the liver and thymus of
      recipient mice. c-kit+ cells isolated from the bone marrow entered and expanded
      prominently in both the liver and thymus, whereas c-kit+ cells from the thymus
      did not do so at all. On the other hand, c-kit+ cells isolated from the liver and
      spleen showed an intermediate pattern, namely, they took a long time to enter and
      expand in the liver and thymus of recipient mice. All of these c-kit+ cells had
      the potential to give rise to lymphoid cells, which were specific to the liver
      and thymus, respectively. We previously showed that progenitor cells for
      extrathymic T cells in the liver and those for conventional T cells in the thymus
      are not always supplied by the bone marrow, as shown by experiments using
      parabiosis. Taken together with those previous data, the present results suggest
      that c-kit+Lin- cells isolated from various immune organs have organ specific
      properties.

PMID- 10901597
TI  - Hydroxyurea therapy in paraparesis and cauda equina syndrome due to
      extramedullary haematopoiesis in thalassaemia: improvement of clinical and
      haematological parameters.
AB  - Patients with beta-globin disorders show amelioration of clinical condition by
      sustained synthesis of fetal haemoglobin in adult life. We report data on a
      patient with beta(o)-thalassaemia genotype and thalassaemia intermedia clinical
      phenotype. He received therapy with hydroxyurea (20 mg/kg/d) because of the
      presence of extramedullary masses causing paraparesis, neurogenic bladder and
      impotence. During therapy, the patient showed an improved clinical picture and a
      significant increase in total Hb (from 71.8 to 103.2 g/L) and a gamma/alpha
      globin synthetic ratio (from 0.39 to 0.68). The myelosuppressive effect of
      hydroxyurea was revealed by a decrease in CFU-GEMM, BFU-E, and CFU-GM. Therefore
      hydroxyurea can be effective in the treatment of patients with extramedullary
      haematopoiesis (EMH) who are not transfusion-dependent and cannot be treated with
      radiotherapy.

PMID- 10901598
TI  - Rarity of microsatellite alterations in patients with paroxysmal nocturnal
      haemoglobinuria.

PMID- 10901599
TI  - Fulminant thrombotic thrombocytopenic purpura in two patients with systemic lupus
      erythematosus and phospholipid autoantibodies.

PMID- 10901600
TI  - Class I and II posterior composite resin restorations after 5 and 10 years.
AB  - The aim of the present study was to compare and evaluate Class I- and Class II
      restorations performed in two different composite posterior materials after 5 and
      10 years. Both materials were introduced in 1983 and adapted to stress-bearing
      restorations. The only difference between the two materials was that one
      contained barium-aluminium silicate, which made the material radiopaque. All 137
      restorations were performed according to standardized clinical procedures by two
      experienced clinicians and placed in premolars (59) or molars (78). Forty-five of
      the restorations were Class I and 92 Class II. The restorations were followed for
      the first 5 years according to the U. S. Public Health Service (USPHS) evaluation
      criteria. After 10 years an evaluation based on the documentation sent in by the
      patient's present dentist was made. Of the original 137 restorations, 127 could
      be examined after 5 years and 117 after 10 years. The evaluation showed that
      after 5 years, 114 of the examined restorations were in clinical function and
      after 10 years 92, which means 90 and 79 per cent respectively, of the
      restorations evaluated.

PMID- 10901601
TI  - Treatment of class II furcation defects using resorbable and non-resorbable GTR
      barriers.
AB  - The present study was performed to evaluate the therapeutic effect of a
      resorbable matrix barrier (test) compared to a non-resorbable barrier (control)
      on the healing of periodontal tissues in class II furcation defects. Eleven
      patients, each with two class II furcation defects, underwent guided tissue
      regeneration surgery. Random selection was used to decide in which of the two
      sites in each patient test barrier and in which control barrier would be placed.
      Clinical measurements of the Plaque Index, the Bleeding Index, the Position of
      the Gingival Margin, as well as Vertical and Horizontal Probing Attachment Levels
      were made. Whether the barriers were exposed and adverse events were also
      recorded. It was demonstrated that both procedures led to clinical improvement at
      the furcation sites. Nine out of eleven defects treated with the test barrier
      showed improvement while 7 out of 11 achieved the same goal with control barrier.
      None of the improved sites, though, was completely closed. The conclusion was
      that within the limits of this study, resorbable test barrier can be used for
      guided tissue regeneration (GTR) in class II furcation defects with at least as
      good results as those achieved with non-resorbable control barrier but with the
      additional benefit of only one operation.

PMID- 10901602
TI  - Presence of orofacial pain and temporomandibular disorder in fibromyalgia. A
      study by questionnaire.
AB  - The objective of this study was to evaluate subjective symptoms from the
      temporomandibular system in patients with fibromyalgia. Two hundred and thirty
      seven individuals with fibromyalgia affiliated to the Stockholm Rheumatologic
      Association were included in the study. A questionnaire about symptoms of
      temporomandibular disorders (TMD) was mailed and returned by 191 (81%). The
      participants reported frequent and severe symptoms of TMD, 94% reported local
      pain from the temporomandibular system with a mean duration of 12 years. The most
      frequent sites were the temple, temporomandibular joint and neck regions. General
      body pain had a significantly longer duration than TMD, which indicates that
      fibromyalgia starts in other parts of the body and later extends to the
      temporomandibular region. The severity of general pain scored significantly
      higher than local pain, but there was a significant positive correlation between
      the two conditions. High frequency, 73-78 %, of headache, facial pain and
      tiredness of the jaws was found and about fifty percent of the patients also
      complained about difficulties to open the mouth and to chew. Fibromyalgia is thus
      a probable cause of TMD. In conclusion this study shows that patients with
      fibromyalgia often suffer from symptoms of TMD, and that the intensity of the
      pain is correlated to general body pain. These findings indicate that
      fibromyalgia is one of the causes of TMD.

PMID- 10901604
TI  - Malocclusion and the need for orthodontic treatment in 9-year-old immigrant
      children in Stockholm, Sweden.
AB  - In this study the prevalence of malocclusion and the need for orthodontic
      treatment were studied from objective and subjective aspects in 174 immigrant
      children (89 boys and 85 girls). At the time of the study the children were 9
      years of age. The objective need for orthodontic treatment was judged according
      to the 5-point scale of the Swedish National Board of Health and Welfare
      (Medicinalstyrelsen 1966). No need for treatment (grade 0) was observed in 11% of
      the children and only minor treatment need (grade 1) in 29%. A desirable need for
      treatment (grade 2) was found in 28% of the children at the time of the
      examination and an urgent need for treatment (grades 3 and 4) in 32%. Twenty per
      cent of those with a desirable need for treatment (grade 2; 6% of all the
      children) will probably develop an urgent need for treatment when the mixed
      dentition is replaced by the permanent dentition. 56% of the children were not
      interested in orthodontic treatment, and 63% found the arrangement of their teeth
      attractive. These results are discussed in relation to earlier Scandinavian
      epidemiological studies.

PMID- 10901603
TI  - Symptoms and signs of temporomandibular disorders before, during and after
      orthodontic treatment.
AB  - The relationship between orthodontic treatment and symptoms and signs of
      temporomandibular disorders (TMD) was studied prospectively and longitudinally in
      65 adolescent girls with Class II malocclusion. The subjects received orthodontic
      fixed appliance treatment with the straight-wire technique combined with or
      without extractions and were examined for symptoms and signs of TMD before,
      during, after, and finally one year post-treatment. Both symptoms and signs of
      TMD showed considerable fluctuations over the three-year period within the
      individuals. The general tendency was a decreased prevalence of symptoms of TMD
      over the three years. The prevalence of pain on mandibular movement and
      tenderness to palpation of the masticatory muscles was significantly less common
      during and after orthodontic treatment than before. Clinically registered TMJ
      clicking increased slightly over the three year period. One orthodontic treatment
      effect when normalizing Class II malocclusions with fixed appliances was a
      decreased prevalence of functional occlusal interferences. We concluded that the
      orthodontic treatment either with or without tooth extractions did not increase
      the risk for TMD or worsen pre-treatment signs of TMD. Subjects with Class II
      malocclusion and pre-treatment signs of TMD of muscular origin seemed rather to
      benefit functionally from orthodontic treatment in a three-year perspective.

PMID- 10901605
TI  - T-cell co-signalling molecules in graft-versus-host disease.
AB  - Allogeneic stem cell transplantation (allo SCT) is now frequently performed for
      the treatment of haematological malignancies and aplastic anaemia. However, graft
      versus-host disease (GVHD) is still the major complication after allo SCT,
      producing immune deficiency, infection, organ damage and, occasionally, patient
      death. The antigen-specific signal mediated by the T-cell receptor (TCR) is
      essential for activation of T-cells; however, additional co-stimulatory signals
      are required for complete T-cell activation. Therefore, blocking strategies of co
      stimulatory signals have been evaluated as targets of therapeutic intervention
      for GVHD after allo SCT. In a mouse bone-marrow transplantation (BMT) model, the
      administration of CTLA4-Ig, which blocks the interaction of CD28 on T-cells and
      B7 molecules on antigen-presenting cells (APCs), can prolong survival of allo BMT
      recipients, although this effect was not complete. In addition, the anti-CD40L
      (CD154) monoclonal antibody (mAb), which can interfere with the interaction of
      CD154 on T-cells and CD40 on APCs, can induce long-term graft survival in the
      murine model. Combined administration of CTLA4-Ig and anti-CD40L mAb can prevent
      allograft rejection in primates. Therefore, it seems the most powerful method to
      prevent the alloimmune response in vivo. The Fas/Fas ligand pathway is also
      involved in pathogenesis of GVHD. Anti-FasL mAb can reduce the mortality of GVHD
      and improve intestinal lesions. Recently, it was reported that donor bone marrow
      treated ex vivo using CTLA4-Ig reconstituted haematopoiesis in vivo with a
      relatively low risk of GVHD in human allo BMT. Therefore, selective blocking
      strategies for T-cell co-signalling might be useful for the prevention of GVHD in
      human allo SCT.

PMID- 10901606
TI  - F cells, fetal hemoglobin levels, lymphocyte subsets, and frequency of crises in
      sickle-cell disease in Kuwait.
AB  - In vitro, fetal hemoglobin (Hb F) inhibits the aggregation of Hb S, and this may
      be clinically significant. Alterations in B and T lymphocytes seen in sickle-cell
      disease may be important in the immune deficit in these patients. We examined 16
      patients with repeated crises (6 females and 10 males, age 9.3 +/- 3.4 years) and
      15 patients with infrequent crises (9 females and 6 males, age 7.1 +/- 3.8 years)
      to determine the relationship between F cells, Hb F levels, lymphocyte subsets,
      and the frequency of crises. The proportion of CD2 and CD3 lymphocytes was
      significantly lower (P=0.015 and <0.0001, respectively) in both groups of
      patients than controls. CD4 lymphocytes were significantly lower (P = 0.018) and
      CD19 significantly higher (P = 0.007) than controls. CD45RO levels in both groups
      of patients were comparable with matched controls but significantly lower (P =
      0.002) than adult values. Hb F levels in patients with and without frequent
      crises were comparable (P = 0.067). However, F cells in patients with infrequent
      crises were significantly higher than in patients with frequent crises (P<0.01).
      Alteration in the lymphocyte subsets did not correlate with the frequency of
      crisis in these patients.

PMID- 10901607
TI  - The platelet alpha2-integrin (GPIa) nucleotide-807 polymorphism is not associated
      with a risk for maternal-fetal human platelet antigen-5 incompatibility.
AB  - Alloimmunization against human platelet antigen (HPA)-5 may lead to neonatal
      alloimmune thrombocytopenia. The HPA-5 dimorphism is expressed on the platelet
      alpha2beta1 integrin. The density of this receptor is associated with another
      dimorphism of the 2beta1 integrin (nucleotide-807C/T). We hypothesized that anti
      HPA-5b-induced neonatal thrombocytopenia is more likely to occur if the receptor
      is expressed at high than at low levels. Among 933 mother-child pairs, we
      identified 79 HPA-5aa mothers giving birth to a HPA-Sab offspring. Seventeen
      mothers had HPA-5b antibodies, but the offspring had a normal platelet count. We
      genotyped the offspring and mothers for the alpha2-807C/T dimorphism to evaluate
      its relationship to antibody formation. There was no difference between the
      frequency of the 807C/T dimorphism among children delivered from alloimmunized
      mothers and those from mothers without antibodies (P>0.3). The frequency of the
      807C/T dimorphism was not different in the two maternal groups. In three maternal
      fetal incompatibilities, we observed at delivery normal platelet counts of
      platelets typed HPA-5b-alpha2807T, despite increasing maternal antibody titers
      during the pregnancy. Our data do not support the hypothesis that the 807C/T
      dimorphism in the HPA-5ab children is a predisposing factor to either elicit
      alloimmunization against HPA-5b or for neonatal alloimmune thrombocytopenia.

PMID- 10901608
TI  - CD66 expression in acute leukaemia.
AB  - Antibodies against CD66 identify antigens from the carcinoembryonic antigen (CEA)
      family of proteins, which belong to the immunoglobulin gene superfamily. Despite
      being usually restricted to cells of myeloid or monocytic origin, CD66 expression
      has also been reported in blasts from children with B-cell lineage acute
      lymphocytic leukaemia (ALL). An analysis of the CD66 expression was undertaken in
      a series of acute leukaemia patients. Antigenic expression was analysed using
      triple combinations of monoclonal antibodies (mAbs) in forty-five patients. The
      CD66 Kat4 fluorescein isothiocyanate clone was purchased from Dako (Glostrup,
      Denmark). CD66 was expressed in 2 of 29 patients with AML (acute myeloblastic
      leukemia) (6.8%) and in 8 of 12 patients with B-cell lineage ALL (66.7%;
      P<0.001); in blast crisis (BC) of chronic myelocytic leukaemia (CML), CD66 was
      expressed in two patients with lymphoid BC but not in the two with myeloid BC.
      The co-expression of CD66 with other myeloid antigens was observed in all CD66+
      ALL/ Ly-BC cases tested: CD 13 in six patients, CD33 in seven and CD117 in two
      patients. The CD66 expression is more frequent in ALL than in AML. Furthermore,
      we analysed minimal residual disease (MRD) in eight patients in complete
      remission. CD66 expression was associated with an abnormal B-cell differentiation
      pattern and with increases in CD34/CD19+ cells in all but one case. These
      findings suggest that an aberrant expression of CD66 could be used to investigate
      MRD in ALL. The association between CD66 reactivity and bcr-abl in adult ALL
      remains to be investigated.

PMID- 10901609
TI  - ASHAP--an effective salvage therapy for recurrent and refractory malignant
      lymphomas.
AB  - BACKGROUND: This study was performed to examine the efficacy and toxicity of the
      combination of adriamycin (ADR), methylprednisolone (solumedrol), cytarabine (Ara
      C), and cisplatin (CDDP) in patients with recurrent and refractory malignant
      lymphomas. PATIENTS AND METHODS: Sixty-five patients with Hodgkin's disease (HD)
      (n=14) or non-Hodgkin's lymphomas (NHL) (n = 51) were enrolled in the study. The
      ASHAP therapy consisted of ADR (40 mg/m2 by continuous infusion (CI) over 96 h),
      methylprednisolone (500 mg i.v., days 1-5), Ara-C (2 g/m2 as a 2-h infusion on
      day 5), and CDDP (100 mg/m2 by CI over 96 h). RESULTS: Twenty-five patients (38%)
      achieved complete remission (CR) and 20 (31%) were taken into partial remission
      (PR) for an overall response rate of 69%. Thirty-two patients with CR or PR
      following ASHAP underwent high-dose therapy (HDT) with subsequent hematopoietic
      stem cell transplantation. After a median follow-up of 52 months, 13 patients are
      in continuous CR (CCR), the 3-year event-free survival (EFS) was 30% for
      responders and 21% for all patients. The median overall survival (OS) was 12
      months (range 0-70 months), and the OS rate after 3 years was 32%. Unfavorable
      prognostic factors for EFS and OS by univariate analysis were an elevated value
      of the serum lactate dehydrogenase and refractory lymphoma. The most frequently
      observed side effects following ASHAP were leukocytopenia and thrombocytopenia of
      World Health Organization (WHO) grades III/IV in approximately 80% of all
      courses. Non-hematological toxicities such as gastrointestinal side effects,
      infections, mucositis, renal and neurotoxicity occurred more rarely and reached
      WHO grades III/IV only occasionally. No treatment-related mortality with ASHAP
      was observed. CONCLUSIONS: ASHAP is an effective and moderately toxic salvage
      therapy for patients with recurrent or refractory HD and NHL. The results in
      patients responding to ASHAP and afterwards undergoing HDT with stem cell support
      are comparable with other established protocols and indicate an improvement in
      survival if HDT is carried out as intensification.

PMID- 10901610
TI  - Myeloproliferative disorders: complications, survival and causes of death.
AB  - This retrospective single-center study compared thromboembolic and hemorrhagic
      complications, survival and causes of death in a cohort of 102 consecutive
      patients with myeloproliferative disorders (MPD). We included 17 patients with
      essential thrombocythemia (ET), 59 with polycythemia vera (PV), and 26 with
      osteomyelofibrosis (OMF). The median follow-up was 3.7 years. Estimated 8-year
      probability of complications for the entire cohort was 80 +/- 11% (95% confidence
      interval), without significant differences among MPD subgroups. The rate of
      thromboembolic complications, expressed as the number of events per 100 patient
      years, was 16.7 for patients with PV, 13.8 for OMF, and 7.5 for ET. Fifty-four
      percent of thromboembolic events in PV involved cerebral or limb arteries. The
      rate of bleeding complications was highest in patients with OMF (31.8 per 100
      patient years), followed by ET and PV (11.8). Ninety percent of bleeding episodes
      affected the skin. mucosal membranes, and the gastrointestinal tract. Eight-year
      survival was highest in ET with 91 +/- 17%, followed by PV (66 +/- 18%) and OMF
      (40 +/- 31%) (P< 0.01). Twenty-four patients died during the observation period,
      and fatal thrombosis (in five patients) represented the leading cause of death.
      Only two patients with MPD died from fatal hemorrhage and one from acute
      leukemia. We conclude that survival is highest in ET and lowest in OMF. Both
      thromboembolic and hemorrhagic complications are frequent. However, thrombosis
      appears to be more often fatal than bleeding complications. Prophylaxis of
      thromboembolic events remains a key issue in the management of MPD.

PMID- 10901611
TI  - Overexpression of bcl-2 in transient abnormal myelopoiesis associated with Down
      syndrome.
AB  - Transient abnormal myelopoiesis (TAM) is a haematological complication found in
      Down syndrome. To determine the mechanisms of sustained proliferation of TAM
      cells, we studied the expression of apoptosis-related proteins, such as bcl-2,
      Fas (APO-1/CD95) and p-53, in peripheral blood cells from a new-born infant with
      Down syndrome and TAM. Using flow cytometry, peripheral blood mononuclear cells
      (PBMCs), consisting mostly of blast cells, showed marked expression of bcl-2
      protein but not of Fas or p-53 products. DNA gel electrophoresis of PBMCs,
      cultured in the absence of serum factors, revealed no marked fragmentation. Our
      findings suggest that bcl-2 overexpression may be associated with prolonged cell
      survival of TAM cells.

PMID- 10901612
TI  - Reactive hemophagocytic syndrome as a presenting feature of Hodgkin's disease.
AB  - We report the case of a 60-year-old man with fever of unknown origin, severe
      pancytopenia, and rapidly developing splenomegaly due to reactive hemophagocytic
      syndrome and Hodgkin's disease. Reactive hemophagocytic syndrome is often rapidly
      fatal and, once this diagnosis is considered, an underlying infection or
      malignancy should be treated promptly. An extensive search of the literature
      revealed only two other cases of reactive hemophagocytic syndrome and Hodgkin's
      disease. This is the only reported patient who survived after being diagnosed as
      having reactive hemophagocytic syndrome and Hodgkin's disease.

PMID- 10901613
TI  - Persistent polyclonal B-cell lymphocytosis--an important differential diagnosis
      of B-cell chronic lymphocytic leukemia.
AB  - Over the last 17 years, 83 cases of polyclonal B-cell lymphocytosis (PPBL) have
      been published. This rare hematological disorder of unknown etiology is
      characterized by morphologically atypical lymphocytes, polyclonal immunoglobulin
      M production in association with smoking, female gender, and HLA-DR7 phenotype.
      We studied another male patient with PPBL. In contrast to normal B-cells, PPBL
      cells showed no response to interleukin-4 with regard to CD23 and human leukocyte
      antigen-DR expression. F2mu antibodies failed to co-stimulate interleukin-4
      mediated CD23 expression. Crosslinking membrane immunoglobulin M receptors by
      F2mu resulted in elevated human leukocyte antigen-DR expression but did not
      induce in vitro proliferation of PPBL cells. This indicates a different
      activation and differentiation status than normal B-cells.

PMID- 10901614
TI  - Successful treatment and re-treatment of resistant B-cell chronic lymphocytic
      leukemia with the monoclonal anti-CD 20 antibody rituximab.
AB  - We report on two patients with chemoresistant B-cell chronic lymphocytic leukemia
      who were treated successfully with the monoclonal anti-CD 20 antibody rituximab.
      Both patients suffered from severe thrombocytopenia requiring platelet
      transfusions over a period of several months. Neither chemotherapy nor
      immunosuppressive agents (corticoids, immunoglobulins) were effective. After four
      doses of rituximab (375 mg/m2 weekly), both patients recovered within a few weeks
      to hematological partial remission. One patient was re-treated successfully three
      times after relapses. Both patients were premedicated with prednisone (100 mg) 30
      min prior to the infusion to prevent cytokine release and the antibody infusions
      were well tolerated.

PMID- 10901615
TI  - Human herpes virus-8 associated with two cases of primary-effusion lymphoma.
AB  - Primary-effusion lymphoma (PEL) is a rare form of non-Hodgkin's lymphoma which
      predominantly occurs in patients with acquired immunodeficiency syndrome and is
      characterized by the presence of a malignant effusion in one or more of the body
      cavities, generally in the absence of a primary tumor mass. Recently, we
      encountered two cases of PEL presenting as cardiac tamponade. In both cases, a
      diagnosis of diffuse large B-cell lymphoma was made by examination of the
      pericardial fluid. Because human herpes virus-8 (HHV-8) antibodies were positive
      and human immunodeficiency virus antibodies were negative, HHV-8 seemed likely to
      be an etiologic agent for the PEL. One of the two patients (case 1) was not
      treated for religion reasons and died. The other (case 2) achieved complete
      remission after treatment using the CHOP regimen and is alive at present. The
      prognosis of this disease is believed to be poor, therefore more cases should be
      collected to establish reliable therapy for PEL.

PMID- 10901616
TI  - Disseminated infection by Scedosporium prolificans: an emerging fatality among
      haematology patients. Case report and review.
AB  - We describe a case of proven disseminated infection by Scedosporium prolificans
      in a profoundly neutropenic patient. The patient presented with a fever
      unresponsive to broad-spectrum antibiotics, endophthalmitis, respiratory failure
      and a renal abscess. The organism was isolated from bronchoalveolar lavage fluid
      and from pus obtained through a sterile puncture. Review of the English-language
      literature identified 28 additional cases; these occurred exclusively in severely
      neutropenic patients (predominantly leukaemia) and in transplant recipients.
      Apart from two or possibly three cases, dissemination was uniformly fatal due to
      persistent neutropenia and inherited resistance of these pathogens to currently
      available antifungal drugs. At present, the optimal treatment of S. prolificans
      infections is unknown, but reversal of the underlying deficient immune status
      appears of great importance.

PMID- 10901617
TI  - Indicators of L-arginine metabolism and cardiovascular risk factors--a cross
      sectional study in healthy middle-aged men.
AB  - This study examines the relationship between traditional risk factors of coronary
      artery disease and indicators involved in the metabolism of L-arginine (plasma
      and urine L-arginine, plasma L-citrulline, serum creatinine and urine orotic
      acid). Our study population consisted of 40 healthy male volunteers aged between
      35 and 55 years. We found an inverse association between serum creatinine and
      blood pressure, between plasma L-citrulline and blood pressure, as well as
      between urine L-arginine and blood pressure. We also found a positive association
      between plasma LDL-cholesterol and urine L-arginine and a negative correlation
      between plasma L-arginine and LDL-cholesterol. Orotic acid measured from urine
      was not associated with any of the indicators of L-arginine metabolism. Our
      results indicate that L-arginine metabolism is of profound significance for
      cardiovascular health. However, our study does not answer questions relating to
      causality. Further studies are needed to clarify the causal relationship between
      cardiovascular risk factors, especially elevated blood pressure and high LDL
      cholesterol, and indicators of L-arginine metabolism.

PMID- 10901618
TI  - Anaerobic accumulation of amino acids in rice roots: role of the glutamine
      synthetase/glutamate synthase cycle.
AB  - Accumulation of amino acids was studied in rice roots of 3-day-old seedlings
      subjected for 48h to anaerobic conditions. Alanine and Gaba were the main amino
      acids accumulated under anoxia. Their synthesis was strongly inhibited by MSX and
      AZA, inhibitors of glutamine synthetase and glutamate synthase. These activities
      increased after 8h of anaerobic treatment and, by immunoprecipitation of 35S
      labeled proteins, it was shown that glutamine synthetase and ferredoxin-dependent
      glutamate synthase were synthesized during the treatment. These findings indicate
      that the glutamine synthetase/glutamate synthase cycle play an important role in
      anaerobic amino acid accumulation.

PMID- 10901619
TI  - The peptides of alpha-aminosuberic acid I. New intermediates for synthetic
      studies.
AB  - The paper describes the synthesis of alpha-aminosuberic acid derivatives suitable
      for the synthesis of peptides. These include Z-, Boc- and Fmoc-protection on the
      alpha-amino group, benzyl ester, Boc-hydrazide and Z-hydrazide as well as the
      free carboxylic function in the side chain, and methyl ester, benzyl ester or
      free alpha-carboxylic group. Their use is demonstrated on the synthesis of the
      respective derivatives of Asu-Val-Leu. The enzyme catalyzed reaction was
      successfully used both as a route to L-Asu from the D,L-compound as well as for
      the direct synthesis of the optically active tripeptide derivative from the Z-D,L
      Asu-OH.

PMID- 10901620
TI  - Inducible nitric oxide synthase activity in colon biopsies from inflammatory
      areas: correlation with inflammation intensity in patients with ulcerative
      colitis but not with Crohn's disease.
AB  - Nitric oxide synthase (NOS) activities are responsible for the enzymatic
      conversion of L-arginine into NO and L-citrulline. Relatively low amounts of NO
      are produced in intestinal epithelial cells or are released from nerve endings.
      The effects of NO production are related to the maintenance of epithelial
      integrity and permeability. A pathological role of an increased NO production has
      been suggested to play a role in models of experimental colitis. In humans, NOS
      activity in colon mucosa from patients with ulcerative colitis is clearly
      increased when compared with the activity of the control group. In contrast, an
      increase of NOS activity in the colon mucosa from patients with Crohn's disease
      remains controversial. In the present work, we have measured NOS activity in
      colon biopsies originating from the control group (n = 16), from patients with
      ulcerative colitis (n = 23) and Crohn's disease (n = 17) using the radiochemical
      method of the conversion of L-[guanido-14C] arginine into radioactive L
      citrulline. In the control group, NOS activity was mainly of the inducible type
      (88% of total NOS activity) since it was characterised by its insensibility to
      the absence of calcium in the assay medium. In colon biopsies originating from
      patients with ulcerative colitis, inducible NOS activity was increased 3 fold (p
      < 0.005) and in patients with Crohn's disease, inducible NOS activity was
      increased 5 fold (p < 0.005). Correlations between NOS activity in colon biopsies
      and the intensity parameters of the disease i.e. Truelove index, endoscopic score
      and histological parameters were evidenced in patients with ulcerative colitis.
      In contrast, in patients with Crohn's disease, the high inducible NOS activity
      was not correlated with any intensity parameters of the disease. From these data,
      we concluded that although inducible NOS activity was increased several fold in
      colon biopsies originating from patients with both ulcerative colitis and Crohn's
      disease, a correlation between this activity and the severity of bowel
      inflammation was not found in either cases.

PMID- 10901621
TI  - The effects of thiopentone on free intracellular amino acids in polymorphonuclear
      leucocytes.
AB  - Previous studies have shown the inhibitory effects of thiopentone on
      polymorphonuclear leucocyte (PML) function. However, major biochemical mechanisms
      which have been involved are still unknown. The aim of this study was therefore
      to investigate thiopentone's effects on intracellular amino acid metabolism in
      PML using both advanced PML separation- and HPLC techniques, especially developed
      for this purpose and precisely validated in our institute. Overall, our study
      indicates important dose-dependent alterations of free intracellular amino acid
      metabolism following thiopentone treatment and draw attention to the biochemical
      mechanisms which may be involved in both thiopentone-induced modulation in PML
      function and cellular immunocompetence.

PMID- 10901622
TI  - Chemical and toxicological studies of products resulting from sorbic acid and
      methylamine interaction in food conditions.
AB  - Sorbic acid has a system of conjugated double bonds which makes it able to
      undergo nucleophilic addition reactions with certain functions. The interactions
      between sorbic acid and an amine present in the endogenous constituents of food
      were quantified. We demonstrated the formation of new products and studied the
      underlying mechanisms using ethyl sorbate and various amines. HPLC, GC, GC-SM and
      NMR analyses of the reaction mixes enabled the isolation and identification of
      the products. The addition reactions led, at 20 degrees C, to linear monoadducts
      and, at 50 degrees C, to cyclic derivatives resulting from double addition.
      Mutagenesis studies, involving Ames test and genotoxicity studies with HeLa cells
      and on plasmid DNA, in cyclic interaction products, showed that none of the
      products studied presented neither mutagenic nor genotoxic activities.

PMID- 10901623
TI  - Consequences of renal mass reduction on amino acid and biogenic amine levels in
      nephrectomized mice.
AB  - Amino acid and biogenic amine changes were investigated in nephrectomized mice
      ten days postsurgery. Uremic mice exhibited changes in amino acid concentrations
      in plasma, urine and brain. Particularly plasma methionine, citrulline and
      arginine levels were significantly enhanced in nephrectomized mice compared to
      controls whereas serine was decreased. Urinary excretion of methionine,
      citrulline and alanine was higher in nephrectomized mice compared to controls
      whereas many amino acids were increased in brain of nephrectomized mice. Brain
      and urinary amino acid changes were more pronounced in the 75% than in the 50%
      nephrectomized mice. Brain norepinephrine and dopamine and its metabolites 3,4
      dihydroxyphenylacetic acid and homovanillic acid were significantly increased
      whereas serotonin was decreased comparing the 75% nephrectomized mice to the sham
      operated mice. This study demonstrates that at very early stages of renal
      insufficiency, specific amino acid and biogenic amine changes occur in plasma,
      urine and brain. These alterations might depend qualitatively and quantitatively
      on the degree of functional renal mass reduction.

PMID- 10901624
TI  - Identification of the site of glucocorticoid action on neutral amino acid
      transport in superficial nephrons of rat kidney.
AB  - Glucocorticoid hormones enhance the reabsorptive capacity of filtered amino acids
      in rat kidney, as it was shown in previous in vivo clearance experiments. In the
      present study, the site of glucocorticoid action on neutral amino acid transport
      in superficial nephrons of rat kidney was investigated using in vivo
      micropuncture technique. Adult female Wistar rats were treated with dexamethasone
      (DEX), and fractional excretion of L-glutamine (L-Gln) and L-leucine (L-Leu) were
      determined and related to inulin after microinfusion into different nephron
      segments. DEX reduced fractional excretion of both neutral amino acids as a sign
      of enhanced reabsorptive capacity. The site of main DEX action on L-Leu
      reabsorption has been localized in the proximal straight tubule. However, in the
      case of L-Gln, the inhibition of gamma-glutamyltranspeptidase (gamma-GT) by
      administration of acivicin indicated the importance of this brush border enzyme
      in reduced L-Gln excretion. DEX enhanced gamma-GT activity by tubular
      acidification. It can be presumed a DEX-inducible transport system for neutral
      amino acids mainly localized in proximal straight tubules of rat kidney.

PMID- 10901625
TI  - Impaired glucose tolerance (IGT) is not associated with disturbed homocysteine
      metabolism.
AB  - Elevated plasma total homocysteine (tHcy) has been suggested to be an additional
      risk factor for cardiovascular disease in subjects with impaired glucose
      tolerance (IGT) and Type 2 diabetes (T2D). In order to investigate whether an
      insulin resistant/chronic hyperinsulinemic situation in male diabetic and
      prediabetic subjects directly influences the tHcy metabolism, fasting tHcy and
      post-methionine load tHcy plasma levels (PML-tHcy) were determined in 15 men with
      IGT, 13 men with newly diagnosed T2D, and 16 normoglycemic controls (NGT).
      Fasting tHcy (IGT, 13.1 +/- 4.6; T2D, 12.8 +/- 4.0; NGT, 10.7 +/- 4.4 micromol/L)
      and PML-tHcy (IGT, 46.5 +/-17.39; T2D, 41.1 +/- 6.8; NGT, 38.0 +/- 9.7
      micromol/L) showed no differences between the groups. Fasting tHcy and PML-tHcy
      correlated with fasting proinsulin (r = 0.395, p < 0.05; r = 0.386, p< 0.05) and
      creatinine (r = 0.489, p < 0.01; r = 0.339, p < 0.05), resp. Multiple regression
      analysis showed only a relationship between fasting tHcy and creatinine. No
      relationships have been found between fasting tHcy and PML-tHcy, resp., and
      indicators of an insulin resistant state, e.g., insulin and proinsulin, as well
      as serum cobalamin and folate concentrations. In conclusion, our data suggest
      that the degree of glucose intolerance has no direct impact on the metabolism of
      homocysteine. However, tHcy levels tend to be elevated with the development of
      nephropathy, indicating an association between tHcy and renal function in these
      subjects.

PMID- 10901626
TI  - Excitatory amino acid stimulation of the survival of rat cerebellar granule cells
      in culture is associated with an increase in SMN, the spinal muscular atrophy
      disease gene product.
AB  - Excitatory amino acids which promote the survival of cerebellar granule cells in
      culture, also promote the expression of the survival of motor neuron (SMN)
      protein. Immunolocalization studies using SMN monoclonal antibody showed that SMN
      is decreased in cultures grown in low K+ or chemically defined medium with
      respect to cultures grown in high K+ medium and that an increase of SMN can be
      induced by treatment of low K+ cultures with glutamate or N-methyl-D-aspartate.

PMID- 10901627
TI  - Restoration of Ayurakitia to generic rank in tribe Aedini and a revised
      definition of the genus.
AB  - Ayurakitia, previously treated as a subgenus of genus Aedes, is restored as a
      genus in tribe Aedini of family Culicidae. Rationale for this action is
      discussed. The genus includes 2 species (griffithi and peytoni) and has been
      reported from Southeast Asia. The most distinctive features of the genus are
      listed. A revised and expanded definition of the genus and illustrations of the
      female and male genitalia, pupa, and 4th-stage larva of the type species are
      provided.

PMID- 10901628
TI  - On Coquilleitidia crassipes, a new record for Macau, with a key to adults of the
      subgenera and species groups of the genus.
AB  - Coquillettidia (Coquillettidia) crassipes is recorded for the 1st time in the
      Territory of Macau, southern China. The systematics of the genus is examined, new
      species groups are proposed, and a key to subgenera and species groups of
      Coquillettidia is provided.

PMID- 10901629
TI  - Cytotaxonomic evidence for the presence of Anopheles nivipes in India.
AB  - Anopheles philippinensis mosquitoes were collected from 5 states in India: Assam,
      Meghalaya, Arunachal Pradesh, Manipur, and Nagaland. Half-gravid females were
      examined for variations in wing venation using the presector dark mark on vein I
      and polytene chromosomes derived from ovarian nurse cells. Polytene chromosomes
      were examined for diagnostic inversions, t on chromosome arm 2 and I on arm 5.
      Based on wing characteristics, both An. philippinensis and An. nivipes were
      identified. Polytene chromosome examinations revealed that all specimens from
      these 2 populations had 2t; 51 inversion genotype, a diagnostic character for An.
      nivipes. The wing character was not diagnostic; therefore, it was concluded that
      all the specimens examined were actually An. nivipes and not An. philippinensis.
      Further, the X chromosome was of x+b type, that is, the standard arrangement with
      reference to the inversion b, reported in the An. nivipes population in Thailand.
      This is the 1st report that unequivocally establishes the occurrence of An.
      nivipes in India and also shows that the adult wing character is not reliable in
      distinguishing An. philippinensis from An. nivipes, as has been observed in
      Thailand.

PMID- 10901630
TI  - Phylogenetic relationships among eighteen neotropical Culicini species.
AB  - The subgeneric relationships among 8 generic and infrageneric taxa of the
      Culicini tribe were examined by cladistic analysis based on 30 larval mouthpart
      characters (maxillae and mandibles) of 7 subgenera of Culex L. and 1 of
      Deinocerites Theobald. We analyzed 18 ingroup species as well as Deinocerites
      melanophylum Dyar and Knab as a sister group, and Aedes taeniorhynchus Wiedemann
      as an outgroup. A parsimony analysis using the Nona program resulted in 2 trees
      each of 109 steps (consistency and retention indices = 0.88). The topologies
      obtained were similar to the current classification of the tribe, based on
      nonexplicit methods mainly including adult characters, with 2 exceptions. In the
      present work, the monophyly of the tribe Culicini (Culex + Deinocerites) was
      supported by 4 synapomorphies. The subgenus Lutzia Theobald formed the most basal
      clade in the tribe Culicini and the placement of Phenacomyia Harbach and Peyton
      as a subgenus was validated by its location as a sister group of the subgenus
      Culex and other subgenera. The subgenus Carrollia Lutz was the most robust taxon,
      supported by 5 synapomorphies, and was congruent with the infragroups of the
      current classification. The relationships among Deinocerites, Anoedioporpa Dyar,
      Microculex Theobald, and Melanoconion Theobald were unresolved, but were placed
      in the most internal clade of the tribe. The 1st exception to the accepted
      classification was the poorly resolved boundary between Anoedioporpa and
      Microculex The 2nd was the strong support (with 11 synapomorphies) for the
      inclusion of Deinocerites as a subgenus of Culex in the Culicini, which is
      proposed here.

PMID- 10901631
TI  - Redescription of the adult and larva and first description of the pupa of
      Anopheles (Kerteszia) laneanus.
AB  - Anopheles (Kerteszia) laneanus is redescribed and compared with other species of
      the subgenus Kerteszia. The pupal stage is described for the 1st time and
      information on bionomics is provided.

PMID- 10901632
TI  - Integrated control of the dengue vector Aedes aegypti in Liu-Chiu village, Ping
      Tung County, Taiwan.
AB  - Because of an inadequate supply of potable water, villagers of Small Liu-Chiu
      Isle, Ping-Tung County, Taiwan, store water in containers supporting a large
      population of Aedes aegypti. In 1989-96, integrated control measures against Ae.
      aegypti were implemented on the basis of community participation. These measures
      included release of mosquito larvivorous fish in the drinking water storage
      facilities, application of larvicides to the water storage facilities in
      vegetable gardens, removal of discarded and unused containers and tires,
      improvement of household water storage facilities, and increase of potable water
      supply. Before implementation of the integrated control measures in 1988, 74% of
      the water-containing vessels were water storage facilities, and 24% of those were
      infested by Ae. aegypti. In 1989, the Breteau index for the entire island,
      indicating the average distribution density for larval Ae. aegypti, was 53.9, as
      compared to an index of 1.2 in 1996. In 4 villages located at the southwest and
      middle of the island, Ae. aegypti nearly became extinct because of the
      enthusiastic participation of the community. Before the implementation of
      integrated control, Ae. aegypti was the dominant species in containers both
      inside and outside the household, but after the integrated control, Aedes
      albopictus became predominant outside.

PMID- 10901633
TI  - Mosquito surveillance in the Demilitarized Zone, Republic of Korea, during an
      outbreak of Plasmodium vivax malaria in 1996 and 1997.
AB  - Since 1993, more than 2,000 cases of vivax malaria have occurred in the Republic
      of Korea in an epidemic that ended nearly 20 malaria-free years. Most malaria has
      occurred in the northwestern part of the country, mainly affecting Korean
      military personnel. As a part of an operational surveillance effort, we sampled
      mosquitoes in and near the Demilitarized Zone (Paju County, Kyonggi Province)
      during the last 2 wk of July in 1996 and from May 15 to September 10 in 1997. The
      1st year, landing collections were done at 5 different sites; the 2nd year,
      carbon-dioxide-baited light traps at 5 sites, larval collections in 10 adjacent
      fields, and landing collections at 1 site in the Demilitarized Zone were
      performed weekly. Of 17 species collected, Anopheles sinensis was consistently
      the most abundant mosquito, comprising 79-96% of mosquitoes. The diel pattern of
      biting by An. sinensis varied by location and season, with the majority of
      individuals biting late at night during warm weather (>20 degrees C) and early at
      night during cool weather. In contrast, Aedes vexans nipponii (the 2nd most
      abundant species) bit in the greatest numbers at the same time all season, from
      2000 to 2300 h. Among the correlates with abundance of An. sinensis were average
      nighttime temperature 2 wk previous to the night in question, wind late at night
      (negatively correlated), and apparent size of the moon (negatively correlated).
      The data showed that the exact number of An. sinensis biting could not be
      estimated from numbers collected in carbon-dioxide-baited light traps. On the
      other hand, a threshold of 15 An. sinensis per trap night corresponded (88%
      accuracy) to a threshold of 12 mosquitoes biting 2 adjacent collectors per night.
      Larval collections were also significantly correlated with landing collections,
      despite inexact sampling methods and separation of the larval habitat from the
      site where landing collections were performed. Operational entomology assets
      using nighttime temperature records, carbon-dioxide-baited light traps, and
      larval collections should be able to target their efforts in Korea more
      efficiently.

PMID- 10901634
TI  - People's knowledge and practice about dengue, its vectors, and control means in
      Brasilia (DF), Brazil: its relevance with entomological factors.
AB  - In South America, the epidemiology and ecology of dengue fever are strongly
      associated with human habits because the vector Aedes aegypti is strictly urban.
      Thus, the evaluation of people's knowledge and practice (PKP) is of great
      importance to improve integrated control measures. A PKP evaluation has been done
      in a suburb of Brasilia. Thirty questions were submitted to 130 habitants about
      income level, education, sources of information, specific knowledge about dengue,
      vector biology, and control measures applied. Other questions were about the
      responsibility of dengue control and the opportunity of applying a fine to people
      who would not cooperate with the control measures. Level of PKP was fairly high,
      either for housekeepers, workers, or students. The mosquito bite was cited as
      source of infection by 60.8% of interviewed people but 22.3% had no knowledge
      about this topic. The most cited symptoms in association with dengue were fever
      (73.1%), headache (66.2%), and rash (35.4%). Knowledge about mosquito biology and
      control was also fairly accurate, as demonstrated by 96.9% of answers.
      Elimination of water containers was the most efficient means according to 73% of
      people. Such action should be done mainly by the citizen (75.3% of answers).
      Despite the good PKP, correlations existed only between the PKP about vector
      biology and presence of potential breeding containers in March, and between the
      PKP about the disease and potential breeding containers in April. In conclusion,
      global educational campaigns may have a real impact on the PKP but this did not
      result in effective control of the mosquito breeding containers by the people.

PMID- 10901635
TI  - Emergence patterns of Culex mosquitoes at an experimental constructed treatment
      wetland in southern California.
AB  - The emergence patterns of mosquitoes inhabiting a 0.1-ha experimental wetland in
      southern California were monitored using emergence traps during the late summer
      and autumn of 1996. Culex erythrothorax was the largest contributor to emerging
      populations, comprising 94% of the total emerged adults with an average emergence
      rate of 59 adults/day/m2. None of the Culex species exhibited a pattern of
      emergence associated with water depth (range: 5-60 cm). Culex quinquefasciatus
      and Cx. tarsalis did not show a pattern of emergence associated with the inflow
      outflow gradient; however, Cx. erythrothorax emerged in higher numbers along a
      transect at the middle of the wetland than from near the inflow and outflow.
      Additionally, the number of emerged Cx. erythrothorax was positively correlated
      with the density of vegetation below emergence traps. The comparatively large
      number of adults emerging from the middle of the wetland was most likely caused
      by a trade-off between an increasing gradient of resource abundance and a
      decreasing gradient of toxic compounds from the inflow to the outflow of the
      small wetland.

PMID- 10901636
TI  - Effects of magnetic fields on mosquitoes.
AB  - Phylogenetically diverse organisms, including some insects, are able to detect
      and respond to magnetic fields comparable to the Earth's magnetic field. Because
      of their tremendous importance to public health, mosquitoes were tested for the
      presence of remanent ferromagnetic material indicative of a biological compass
      and also tested for behavioral responses to magnetic fields. Using a
      superconducting quantum interferometry device, we found that significant remnant
      was probably due to attraction of ferromagnetic dust onto the surface of live or
      dead mosquitoes. Most mosquitoes placed in a 1.0-gauss, uniform magnetic field
      moved until they were oriented parallel to the field. Two of 3 species of
      mosquitoes tested took fewer blood meals in a rotating magnetic field than in the
      Earth's normal magnetic field.

PMID- 10901637
TI  - Colonization and laboratory biology of Aedes notoscriptus from Brisbane,
      Australia.
AB  - Methods are described for the laboratory colonization of Aedes notoscriptus from
      Brisbane, Queensland, Australia. To initiate colonization, efforts were made to
      duplicate the natural environment of this species, including the use of a
      bromeliad as a swarm marker and oviposition substrate. The colony stabilized
      after the F8 with eclosion rates >50%, and an average production of 5,220 adults
      since the F9. The fecundity of Ae. notoscriptus averaged 29.4+/-10.5 eggs (range
      14-57). The average development times from egg hatch to adult were 11 and 20 days
      under typical summer (20.5-28.9 degrees C) and winter (10.1-21.2 degrees C)
      conditions in Brisbane, respectively. This is the 1st published report of the
      colonization of Ae. notoscriptus.

PMID- 10901638
TI  - Amplified esterases B1 and A2-B2 in field populations of Culex pipiens from
      China.
AB  - The main organophosphate (OP) resistance mechanism in the Culex pipiens complex
      is increased activity of esterases A and B. Fourth-stage larvae from 2 field
      populations of C. pipiens from Gaomi and Kunming, China, were compared for
      tolerance to parathion, dichlorovos (OP), and bassa (carbamate) insecticides.
      Both populations were resistant to OPs but not to bassa. Starch gel
      electrophoresis indicated that elevated esterase activity was correlated with OP
      resistance. High frequencies of amplified esterase genes B1 and A2-B2 (0.85 and
      0.50) were discovered in Gaomi and Kunming, respectively. However, only low
      levels of gene amplification were detected.

PMID- 10901639
TI  - Field efficacy of commercial antimosquito products in Illinois.
AB  - We evaluated the efficacy of commercial antimosquito products in field trials in
      Illinois in June 1998 by comparing mosquito landing rates. Products tested were a
      sonic mosquito repeller, an insect killing grid using ultraviolet light and 1
      octen-3-ol as lures, mosquito smoke coils containing a pyrethroid, citronella
      candles, the mosquito plant Pelargonium citrosum, and a N,N-diethyl-3
      methylbenzamide (deet)-impregnated wrist band. The sonic mosquito repeller,
      insect killing grid, and mosquito smoke coils were evaluated in 16 trials over 5
      days; the citronella candles and mosquito plants in II trials over 4 days; and
      the wrist bands in 4 trials on 1 day. In all 3 studies, we compared landing rates
      with the antimosquito products to both positive (topical application of a deet
      formulation) and negative (no treatment) controls. The deet topical repellent had
      a consistently lower landing rate than all the nontopically applied products
      tested. However, the mosquito coils and the deet-impregnated wrist bands did
      significantly reduce mosquito landing rates relative to untreated controls.

PMID- 10901640
TI  - Laboratory evaluations of methylated soy oil and monoterpenes as mosquito
      larvicides.
AB  - The larvicidal toxicities of methylated soy oil (MSO) and surfactant combinations
      were compared to 2 commercially available oil larvicides (Golden Bear Oil 1111
      and Bonide) in standard laboratory bioassays of 4th-stage larvae of Culex pipiens
      Linn. The dose lethal to 50% of the test organisms (LD50) and the dose lethal to
      95% of the test organisms (LD95) values are presented as microliters (microl) per
      beaker (treatment surface area of 54 cm2). The 2 surfactant-MSO mixtures differed
      significantly in their toxicity to Cx. pipiens larvae; 2% Pyroter CPI-40 in MSO
      was more toxic than 2% Pluronic L121 in MSO (LD50 = 3.8 microl per 54 cm2 and
      11.3 microl per 54 cm2, respectively). The 2 most active larvicides were Golden
      Bear Oil (LD50 = 3.6 microl per 54 cm2) and the 2% Pyroter-MSO mixture. These 2
      were not significantly different from each other. Bonide (LD50 = 6.2 microl per
      54 cm2) and the Pluronic L121-MSO mixture (LD50 = 11.3 microl per 54 cm2) were
      less toxic than Golden Bear Oil and the MSO-Pryroter mixture and they were
      significantly different from each other. Bioassays with 4th-stage larvae of
      Anopheles stephensi Liston showed that toxicity of the Pyroter-MSO formulations
      increased about 2-fold from 18 degrees C to 24 degrees C (LD50 = 20.5 microl per
      54 cm2 and 11.8 microl per 54 cm2, respectively). The laboratory bioassays
      suggest that MSO mixed with surfactants are potential mosquito larvicides. We
      also evaluated the influence of the 2 surfactants on the toxicity of 3
      monoterpenes. The larvicidal activity of citral and limonene increased with the
      addition of surfactants, but neither surfactant enhanced the toxicity of cineole.
      All 3 monoterpenes, with and without surfactants, were considered poor candidates
      as surface larvicides because of their high volatilities.

PMID- 10901641
TI  - Response of Culicoides sonorensis (Diptera: Ceratopogonidae) to 1-octen-3-ol and
      three plant-derived repellent formulations in the field.
AB  - The potential attractant 1-octen-3-ol and 3 potential repellents were assayed for
      activity for Culicoides sonorensis, the primary vector of bluetongue virus in
      North America. Collections using octenol were low, but numbers in suction traps
      were greater in the high-octenol treatment (11.5 mg/h) than in the low-octenol
      treatment (1.2 mg/h) or unbaited control for both sexes. Collections using high
      octenol, CO2 (approximately 1,000 ml/min), or both showed octenol alone to be
      significantly less attractive than either of the CO2 treatments and that octenol
      did not act synergistically with this level of CO2. A plant-derived (Meliaceae)
      extract with 4.5% of active ingredient (AI) (Ag1000), heptanone solvent, Lice
      free (2% AI from plant extracts in water), Mosi-guard with 50% Eucalyptus
      maculata var. citriodora Hook extract, and N,N-diethyl-m-toluamide (deet) were
      applied to polyester-cotton coarse mesh nets and deployed in conjunction with
      suction light traps plus CO2. Collections in the trap with deet were 66% lower (P
      < 0.05) than the heptanone and 56% (P > 0.05) less than the untreated (negative)
      control. Relative to deet, collections in the traps with the lice repellent,
      Ag1000, and Mosi-guard were reduced by 15, 34, and 39%, respectively (P > 0.05).
      The method has promise for field screening of potential repellents before on
      animal testing.

PMID- 10901642
TI  - Anopheles kochi in Irian Jaya detected by size polymorphism of polymerase chain
      reaction-amplified internal transcribed spacer unit 2.
AB  - Anopheles kochi is reported for the 1st time from New Guinea, probably introduced
      by aircraft. This Oriental species was originally detected by analysis of
      polymerase chain reaction-amplified rDNA internal transcribed spacer unit 2 (ITS
      2). Identification was confirmed by morphologic examination. Size of ITS-2 is
      presented for 32 species of Australasian and Oriental anophelines to assist
      morphologic identifications for distribution and vector studies.

PMID- 10901643
TI  - The pulvillus and empodium in Culex quinquefasciatus: visualization with the
      light microscope and a study of fine structure with the scanning electron
      microscope.
AB  - The empodia and pulvilli on each postarsus were examined in male and female Culex
      quinquefasciatus. Up to 160x magnification was required to see them clearly under
      the stereo light microscope but they were more readily visible under the compound
      light microscope as slide mounts at 100-200x magnification. Scanning electron
      micrographs of female and male pulvilli showed that they are either well
      developed (females) or inconspicuous (males) and that they consist of setal tufts
      composed of both pointed and trumpet-ended setae. The ultrastructure of the
      pulvilli is described and their possible function in oviposition is discussed.

PMID- 10901644
TI  - Correlated morphologic and genetic diversity among Lutzomyia longipalpis
      (Diptera: Psychodidae) collections in Venezuela.
AB  - Diversity among Lutzomyia longipalpis populations in Venezuela was characterized
      using 2 methods: larval mouthpart morphology-morphometry and isoenzyme
      electrophoresis. Analysis of the results suggested the presence of 2 morpho
      genotypes. The mentum, maxillary comb, mandibular ventral teeth, and adenylate
      kinase and hexokinase enzyme-encoding loci suggested that a population from the
      northwestern Coriano System (Curarigua) is a distinct lineage within the L.
      longipalpis complex. Three widely separated populations from the Llanos
      (savanna), Andes, and northcentral Coastal Cordillera showed no significant
      substructure. These studies provide morphologic markers that are congruent with
      genetic data and suggest that the morphologic markers may be used to characterize
      and differentiate populations within this species complex.

PMID- 10901645
TI  - Digital flexor sheath: repair and reconstruction of the annular pulleys and
      membranous sheath.
AB  - Rupture or transection of the digital pulley may necessitate repair or
      reconstruction to treat symptomatic flexor tendon bowstringing. When
      reconstruction is necessary, intrasynovial tendon grafts may provide superior
      gliding characteristics when compared with traditional extrasynovial tendon
      grafts. Lacerations of the membranous portion of the digital sheath and of
      noncritical annular pulleys usually do not require operative repair.

PMID- 10901646
TI  - Iliac crest autogenous bone grafting: donor site complications.
AB  - Autogenous bone grafting is often done in orthopaedic surgery for a variety of
      conditions. The iliac crest is currently the most common donor site for obtaining
      autogenous bone graft. We searched the literature to summarize reported
      complications related to the donation of autogenous bone from the iliac crest.
      Our review revealed reports of arterial injury, ureteral injury, herniation,
      chronic pain, nerve injury, infection, fracture, pelvic instability, cosmetic
      defects, hematoma, and tumor transplantation. Currently, autogenous bone grafting
      is a necessary part of the treatment of various orthopaedic conditions. Obtaining
      bone from the iliac crest can be associated with significant morbidity. As bone
      grafting technology emerges, the known complications of the current standard
      should be weighed against the risk of alternate therapies.

PMID- 10901647
TI  - Transesophageal echocardiography in quantification of emboli during femoral
      nailing: reamed versus unreamed techniques.
AB  - We quantified the embolic load to the lungs created with two different techniques
      of femoral nailing. Eleven patients with 12 traumatic femur fractures were
      randomized to reamed (7 fractures) and unreamed (5 fractures) groups.
      Intramedullary nailing was with the AO/ASIF* universal reamed or unreamed nail.
      Transesophageal echocardiography (TEE) was used to evaluate the quantity and
      quality of emboli generated by nailing. Data were analyzed using software that
      digitized the TEE images and quantified the area of embolic particles in each
      frame. The duration of each level of embolic phenomena (zero, moderate, severe)
      was used to determine total embolic load with various steps (fracture
      manipulation, proximal portal opening, reaming, and nail passage). Manual grading
      of emboli correlated highly with software quantification. Our data confirm the
      presence and similarity of emboli generation with both methods of intramedullary
      nailing. Unreamed nails do not protect the patient from pulmonary embolization of
      marrow contents.

PMID- 10901648
TI  - Fractures of the ankle: pathogenesis and treatment.
AB  - From the foregoing, one may reduce the following principles for the management of
      ankle injuries: The mechanism of injury and the diagnosis, including ligamentous
      injury, can be made from initial radiographs. A displaced fracture of only one
      malleolus must be accompanied by ligamentous injury of either the deltoid or
      syndesmotic ligaments, or both. When there is only one break in the ring of the
      ankle mortise, there is no potential for significant displacement; thus, ORIF is
      rarely necessary. With two breaks in the ring, the potential for displacement
      exists, even after successful manipulation, which usually makes operative
      treatment a more attractive option. Closed reduction is done by reversing the
      direction of the injuring forces, though it is not necessary to do so in precise
      inverse order to their occurrences. When ORIF is used, all significant malleolar
      fractures should be rigidly fixed to allow early motion, which, along with
      delayed weight bearing, is especially beneficial when comminution of the
      articular surface exists. Syndesmotic fixation is usually unnecessary if the
      malleolar fractures can be reduced anatomically and securely fixed. The
      reduction, whatever technique is used, should result in full congruency of the
      ankle mortise and a level joint line. Trimalleolar fractures, especially when
      they involve more than 25% of the tibial plafond, are much more likely than
      bimalleolar fractures to be associated with posttraumatic arthritis.

PMID- 10901649
TI  - Past, present, and future of the Clinical Orthopaedic Society.

PMID- 10901650
TI  - Arthroscopy of the elbow for synovial chondromatosis.
AB  - Two cases of arthroscopic removal of multiple loose bodies are presented.
      Successful results were achieved, and patients had 4-year follow-up. Both cases
      involved classic manifestations of synovial chondromatosis. Associated
      degenerative changes were present in one case; histologic examination could not
      confirm synovial origin of the disease. Arthroscopy for removal of symptomatic
      loose bodies is an excellent choice as exemplified by these two cases. Care
      should be taken to review histologic findings, which may help in understanding
      the natural history of this type of process.

PMID- 10901651
TI  - Pyrolysis of humic acids from digested and composted sewage sludge
AB  - Humic acids (HAs) were extracted from four digested sewage sludge samples
      composted for four months, one, two and four years. HAs were pyrolyzed at three
      different temperatures applying both conventional and in situ methylation (ISM)
      pyrolysis. The pyrolysates were analyzed using gas chromatography-mass
      spectrometry (GC/MS). Derivatization (ISM) and pyrolysis temperature had dramatic
      effects on the composition and relative amounts of the pyrolysates. Among the
      derivatized HA fragments aliphatic compounds prevailed under all the pyrolysis
      conditions tested. Aromatic substances consisting mainly of guaiacyl-type
      compounds were detected in higher abundances only at elevated temperatures.
      Without ISM the contribution of aromatic structures to the total pyrogram was
      considerably greater than that of the aliphatics. Increase of the pyrolysis
      temperature from 450 degrees C to 600 degrees C had smaller effect on the
      proportions and composition of the compounds studied than increase from 350
      degrees C to 450 degrees C.

PMID- 10901652
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans in Great Barrier Reef
      (Australia) dugongs (Dugong dugon).
AB  - Fat tissue samples from dugong (Dugong dugon) carcasses stranded at three sites
      along the Great Barrier Reef were analysed for polychlorinated dibenzo-p-dioxins
      (PCDDs) and dibenzofurans (PCDFs). Relatively high levels of PCDDs were
      determined in all three dugongs. In particular OCDD, the PCDD/F congener that is
      usually considered the least bioavailable of all 2,3,7,8 substituted congeners,
      was found at levels higher than reported for other marine mammals. Tissue
      accumulation of PCDDs by dugongs may be a consequence of sediment and/or seagrass
      ingestion during feeding, microbial biotransformation of PCDD precursors in the
      animal's hindgut or, alternatively, the possession of a selective degradation
      capability for PCDFs.

PMID- 10901653
TI  - Predicting surfactant modified soil/water distribution coefficients using
      micellar HPLC
AB  - Soil water/distribution coefficients (Kd) have been measured for the partitioning
      of naphthalene, phenanthrene and pyrene between aqueous surfactant solutions and
      a clean soil. The surfactants used are ABA block copolymers constructed from
      ethylene oxide (the monomer used to synthesise the hydrophilic A blocks) and
      propylene oxide (used for the manufacture of the hydrophobic B block). Three of
      these surfactants comprising the same size propylene oxide block but different
      ethylene oxide/propylene oxide ratios were investigated. Increasing amounts of
      surfactant in the system result in a progressive decrease in the Kd values
      signifying an increasing tendency for the hydrophobic solutes to be dispersed in
      aqueous solution due to the action of the surfactant. More significantly for
      equal surfactant doses the most hydrophobic surfactant possessing the lowest
      ethylene oxide/propylene oxide ratio reduces Kd by the greatest amount whereas
      the most hydrophilic surfactant reduces Kd the least. Finally micellar HPLC using
      the above surfactants and hydrophobic solutes was undertaken. Interpolated
      capacity factors evaluated for particular surfactant doses correlated well with
      Kd values calculated for the same surfactant doses. The relationship between Kd
      and capacity was found to be log-linear and the correlation line could be fitted
      to the data obtained for all three surfactants. It is therefore concluded that
      micellar HPLC may be used for preliminary evaluations of the effectiveness of
      particular surfactants proposed for contaminated soils restoration schemes.

PMID- 10901654
TI  - Organochlorines in deep-sea fish from the Nordfjord.
AB  - Hepatic levels of OCs (Organochlorines) were analysed in deep-sea fish from the
      Nordfjord in Norway. Levels of PCBs in the present study exceed background levels
      in fish from Norwegian water by a factor of 1.5 to 50, and DDTs by one to two
      orders of magnitude. DDTs in fish from the Nordfjord have previously been
      attributed to DDT use in fruit orchards. The present levels of DDTs show that the
      decline usually found in biota in Scandinavia since the 1970s is not found in the
      deep-sea fish in Nordfjord. There is no known local PCB source that can explain
      the elevated levels in the present study. This indicates that the fjord
      efficiently accumulates atmospheric contaminants. Chlordanes and HCB were less
      important, and HCHs were not detected.

PMID- 10901655
TI  - Titanium dioxide as photocatalyst on porous nickel: adsorption and the
      photocatalytic degradation of sulfosalicylic acid
AB  - The commonly used photocatalyst, TiO2 (anatase), has been immobilized on porous
      nickel using 3 wt.% polyvinyl alcohol (PVA) as the binder. The results show that
      sulfosalicylic acid (SSal) can be degraded on the developed catalytic system. The
      adsorption characteristics on TiO2-Ni system have been investigated. The
      observance of photocalytic degradation of SSal under pH values and initial
      concentrations can be explained by the adsorption behavior of SSal. The
      parameters of the Langmuir-Hinshelwood expression have been determined by
      different experimental ways and the results are satisfactory.

PMID- 10901656
TI  - The effect of humic acid on uptake/adsorption of copper by a marine bacterium and
      two marine ciliates.
AB  - The effect of humic acid (HA) on Cu uptake by a bacterium and two bacterivorus
      ciliates was investigated. The presence of HA resulted in a statistically
      significant (p<0.001) decrease in Cu associated with bacteria that were exposed
      to 67 microg Cu L(-1). Complexation of Cu appears to lower the availability of Cu
      with respect to bacterial cell surface binding and uptake. For ciliates, 10 mg HA
      L(-1) significantly reduced uptake of Cu by Uronema, but did not reduce uptake of
      Cu by Pleuronema. Uronema exposed to 67 microg Cu L(-1) accumulated 54% less Cu
      when 10 mg HA L(-1) was present (0.50 pg ciliate(-1) vs 0.23 pg ciliate(-1)).
      Uronema feeding on V. natriegens, took up less than half as much Cu as unfed
      Uronema when exposed to Cu without HA (0.41 pg Cu fed ciliate(-1) vs 0.86 pg Cu
      unfed ciliate(-1), but only 40% less when exposed to Cu and HA (0.31 pg Cu fed
      ciliate(-1) vs 0.51 pg Cu unfed ciliate(-1)). The lower % reduction attributable
      to fed ciliates in the presence of HA suggests that some of the Cu associated
      with HA is available through trophic processes.

PMID- 10901657
TI  - Levels and trends of PCDD/Fs and PCBs in human milk in Finland.
AB  - Word Health Organization, WHO/EURO, has coordinated two rounds of follow-up
      studies on levels of PCDDs, PCDFs, and PCBs in human milk which were analyzed as
      two pooled samples from each participating country, one from urban and the other
      one from rural area. Finland has taken part to both of those studies and we are
      now reporting results of all the second round randomly sampled human milk samples
      (84 samples) from Southern (20) and Eastern (64) Finland. The levels of PCDD/Fs
      and PCBs in human milk in Southern Finland were considerably higher than in
      Eastern Finland. The level of PCDD/Fs in human milk in Southern Finland was the
      same as in the Central Europe but the level in Eastern Finland was similar to
      levels in Norway and eastern parts of Europe. The concentrations of PCDD/Fs and
      PCBs showed a significant decrease from 1987 to 1994. Declining of PCDD/Fs and
      PCBs was 36 and 49% in primiparae mothers' milk, respectively. This decrease in
      concentrations of PCDD/F and PCB was slightly greater in Eastern than in Southern
      Finland.

PMID- 10901658
TI  - PCDDs/PCDFs and coplanar PCBs in eels (Anguilla anguilla) from different areas of
      the rivers Havel and Oder in the state of Brandenburg (Germany).
AB  - In 1996 forty-nine eels were caught from different locations along the rivers
      Oder (Hohenwutzen and Schwedt) and from 11 locations along the Havel river. They
      were analysed for PCDDs/PCDFs and the coplanar PCBs (PCB 77, PCB 126, PCB 169).
      Their contribution to 2,3,7,8-TCDD equivalents were estimated. In case of
      PCDDs/PCDFs these amounted between 1.8 and 15.2 pg/g fat (mean 6.1 pg/g; median
      5.2 pg/g), in case of coplanar PCBs between 2.4 and 170.5 pg/g fat (mean 47.7
      pg/g; median 36.1 pg/g). Lakes which are associated with but not directly located
      at the main stream of the river Havel contributed much less to contamination of
      the eels than the river segments situated in the more urbanised or industrialised
      sites along the main river.

PMID- 10901659
TI  - An experimental design to probe the interactions of dissolved organic matter and
      xenobiotics: bioavailability of pyrene and 2,2',5,5'-tetrachlorobiphenyl to
      Daphnia magna.
AB  - Experiments were conducted to probe the interactions between natural dissolved
      organic matter (DOM) and two xenobiotics, and to determine how DOM influences
      their bioavailability. The experimental set-up, using dialysis bags, was designed
      to expose test organisms to the same constant concentration of free dissolved
      chemical, while increasing the concentration of the bound-to-DOM fraction.
      Daphnia magna S. were exposed to pyrene or 2,2',5,5'-tetrachlorobiphenyl in the
      presence of 0, 1, 2, 5, 10 or 20 mg L(-1) of a reference riverine humic acid
      (Suwannee River Humic Acid). The physico-chemical parameters were well
      constrained in the microcosm, demonstrating its potential usefulness. However
      bioaccumulation by D. magna showed important variability between replicate
      treatments, sufficient to mask any trends as a function of DOM concentration. The
      organic-carbon-normalised partition coefficients (K(OC)) ranged from 52000 to
      92000 L kg(-1) for pyrene and from 8200 to 89000 L kg(-1) for 2,2',5,5'
      tetrachlorobiphenyl, with a marked "concentration effect" for the latter
      compound.

PMID- 10901660
TI  - Investigation on the photoreactions of nitrate and nitrite ions with selected
      azaarenes in water
AB  - The photoreactions of selected azaarenes with nitrate and nitrite ions were
      investigated under irradiation at lambda = 313 nm. The excitation of both anions
      leads to several photochemical reactions forming mainly hydroxyl radicals and
      nitrogen oxides. The purification capability of natural waters i.e. the oxidation
      of inorganic and organic substances results from the formation of hydroxyl
      radicals. Nitrated isomers of azaarenes were found among the main products of the
      investigated photoreactions. The nitrogen oxides were responsible for the
      production of nitrated derivatives which possess a high toxic potential. Their
      formation was explained by the parallel occurance of two mechanism, a molecular
      and a radical one. The molecular mechanism became more important with increasing
      ionisation potentials of the azaarenes. The spectrum of oxidized products
      corresponded to the one got in the photoreactions of azaarenes with hydrogen
      peroxide. The formation of several oxidation and nitration products of the
      pyridine ring with its low electron density was explained by the reaction of
      excited states of azaarenes. The photoreactions with nitrite ions only led to the
      formation of oxidized and nitrated products. Nitroso products were not formed.
      The reactivity of nitrogen monoxide is too low for its reaction with the
      azaarenes.

PMID- 10901662
TI  - Environmental fate of amitrole: influence of dissolved organic matter
AB  - In this study the environmental fate of amitrole in terrestrial and aquatic model
      ecosystems was investigated. Under aerobic conditions mineralization of amitrole
      is the main degradation pathway. The experiments revealed that the leaching
      behaviour is low in the presence or the absence of dissolved organic matter (DOM)
      despite the high water solubility due to a strong binding of amitrole to soil
      constituents. Under anaerobic conditions the addition of DOM increases the
      transport of amitrole in soil columns. The tests with water/sediment model
      ecosystems showed that the mineralization of amitrole is lower in comparison to
      aerobic soil experiments. Up to 80.6% of the applied 14C-labelled amitrole
      transfer into the sediment and about 1/3 of this amount formed bound residues,
      which are not extractable.

PMID- 10901661
TI  - The potential contribution of urban runoff to surface sediments of the Passaic
      River: sources and chemical characteristics.
AB  - Urban runoff has been reported as the second most frequent cause of surface water
      pollution in the United States. Due to the incidence of runoff in urban areas, it
      was of interest to estimate the impact runoff may have to recent sediment quality
      within the lower reaches of the Passaic River. Study objectives included i)
      review of recent urban runoff studies to determine the occurrence and pattern of
      distribution of chemicals in runoff; ii)comparison of the "fingerprints" from
      urban runoff studies to the contaminant distributions in surface sediments from
      the River; and iii) estimation of mass loadings to the surface sediments using
      surrogate data. The analyses showed that metals and PAH distributions in the
      sediments were similar to those observed in runoff from diverse locations,
      suggesting that urban runoff composition within the Passaic watershed is similar
      to other urban areas. Mass loading calculations demonstrated that urban runoff is
      a significant source of the metals observed in the sediments, and that PAH and
      DDT sediment loadings could, in some cases, be accounted for by urban runoff.
      Observed sediment loads for PCBs, however, were significantly higher than were
      estimated from urban runoff.

PMID- 10901663
TI  - Fractionation of halogenated organic matter present in rain and snow
AB  - Organic matter in samples of rain and snow from Sweden, Poland, Germany and the
      Republic of Ireland was fractionated by employing a series of filtration,
      purging, evaporation and extraction steps. Determinations of the group parameter
      AOX (adsorbable organic halogens) in aqueous phases and EOX (extractable organic
      halogens) in organic phases showed that halogenated organic matter present in
      bulk precipitation is composed of several different groups of compounds. The
      largest amounts of organically bound halogens were found in fractions of
      relatively polar and non-volatile to semivolatile compounds. In particular, a
      significant part of the AOX could be attributed to alkaline-labile organic bases.
      Gas chromatographic analysis of different organic extracts in the chlorine
      channel of an atomic emission detector (AED) resulted in chromatograms with few
      distinct peaks, and analysis in the bromine channel did not produce any distinct
      peaks. Chlorinated acetic acids were the most abundant halogenated organic acids,
      and chlorinated alkyl phosphates were normally responsible for the largest peaks
      in the chlorine chromatogram of neutral, hexane-extractable compounds. When
      analysing volatiles, 1,4-dichlorobenzene and a thus far unidentified
      chloroorganic compound often caused the largest response in the chlorine channel
      of the AED system.

PMID- 10901664
TI  - Spatial differences of chemical features of atmospheric deposition between rainy
      season and winter in the areas facing to the Japan Sea, Japan
AB  - Atmospheric deposition was collected using filtrating bulk samplers at 32 sites
      in the areas facing to the Japan Sea (AFJS) from April 1991 to March 1994. The
      data were analyzed for winter (January and February) and the rainy season (June
      and July) when the climate is just the opposite. The AFJS was geographically
      divided into five areas, that is western Tohoku (WT), Hokuriku (HR), eastern San
      in (ES), western San-in (WS) and northern Kyushu (NK). WT, HR and ES receive more
      precipitation than other regions in winter. H+ depositions increase in winter
      except NK. This is mainly due to high winter H+ concentrations. In spite of large
      amounts of precipitation in WT, HR and ES in winter, nss-SO4(2-) concentration
      was nearly equal to the average throughout Japan. Namely, nss-SO4(2-) depositions
      in these areas were nearly twice the national mean. In WT, HR and ES, nss-Ca2+
      concentrations in winter are lower than the average of the whole country (less
      than the half). This may be the cause of the lower potentials of neutralization
      and the higher remaining acid concentrations in WT, HR and ES than NK and WS.

PMID- 10901665
TI  - Local circulation and aerosol water-soluble ions--a case study in Taiwan during
      Mei-yu season
AB  - The Mei-yu (plum rain) season is a short but important period when the weather
      changes from spring to summer in Taiwan. In this study, size-segregated aerosols
      were collected alternately at 5 sampling sites in northwestern Taiwan from June
      16 to 24, 1994. For the first time in Taiwan, this study revealed the aerosol
      mass spectra and water-soluble ions in the Mei-yu season. For all samples, a bi
      modal aerosol mass spectra was found with modal diameters at 3.2 and 0.32 microm,
      respectively. The aerosol samples were able to be divided into different groups
      to show their mass and ion spectra according to the calculated 5-hr backward air
      trajectory. The utilization of enrichment factors showed that aerosol Cl-, Na+,
      and Mg2+ for all sizes, and super-micron SO4(2-) were related to the sea. Both
      the scheme of "chlorine loss" (Ohta and Okita, 1990) and a multivariate analysis
      (Thurston and Spengler, 1985) for categorizing water-soluble ions showed that sea
      salts were major contributors in the prevalence of a sea breeze. In contrast, the
      secondary salts were significant for land breeze and a mix of land-sea breeze. In
      conclusion, the influence of local circulation on the distribution of aerosol
      mass and ionic species was found to be prominent.

PMID- 10901666
TI  - Estimation of metal uptake efficiencies from precipitation in mosses in Lithuania
AB  - The main sources contributing to heavy metal content in mosses in Lithuania were
      examined by a comparison of heavy metal concentrations in moss and corresponding
      deposition levels calculated from bulk deposition analysis. Bulk deposition was
      collected in open areas as well as under the canopy of trees. Uptake efficiencies
      in moss were calculated for Cd, Cr, Cu, Fe, Mn, Ni, V and Zn. All elements in
      moss except Pb and Cd appeared to be more or less influenced by sources other
      than air pollution. The general order of this influence on the heavy metal
      content in moss was observed as follows: Ni < V < Cr < Zn < Fe < Mn. The contents
      of Mn and Zn in moss were greatly influenced by leaching from the canopy while Pb
      was the only element which showed a net metal retention by the canopy.
      Concentrations of Fe and Cr in moss were dominating due to contribution from soil
      dust.

PMID- 10901667
TI  - Levels, persistence and bioavailability of organic contaminants present in marine
      harbor sediments impacted by raw sewage.
AB  - As part of a program to investigate the levels, fate and bioaccumulation of
      organic contaminants in a polluted marine harbor, organochlorine compounds
      including the polychlorinated biphenyls (PCBs), dichloro diphenyltrichloroethane
      and metabolites (DDTs), chlordanes, dibenzo-p-dioxins (Ds) and dibenzofurans
      (Fs), polycyclic aromatic hydrocarbons (PAHs) and sulphur hetero cycles were
      analysed in sediments spiked with St. John's Harbor sludge. Winter flounder
      (Pseudopleuronectes americanus) were exposed to these sediments containing six
      levels of harbor sludge during four winter months. Following exposure, sediments
      were reanalysed to investigate the persistence of the contaminants. The primary
      contaminants detected were PAHs (approximately 5000 ng/g), predominantly
      alkylated phenanthrenes, fluoranthene and pyrene; PCBs with a predominance of
      Aroclor 1260 signature (approximately 64 ng/g), DDTs (approximately 5 ng/g),
      hepta and octachloro dioxins and furans (approximately 0.5 ng/g) with very low
      levels of less chlorinated congeners. The PAHs degraded with an estimated half
      life of 2 to 3 months, while no significant degradation could be attributed to
      the other compounds. Bioaccumulation to muscle showed the potential uptake of
      contaminants in biota inhabiting the harbor. A dose-response relationship was
      observed between spiked sediments and the concentrations of PCB congener 153 and
      unresolved congeners 138/163/164 in muscle. Of the dioxins and furans, only 2, 3,
      7, 8-tetrachlorofuran was detectable in muscle and at a similar concentration in
      all exposures indicating a similar bioavailability independent of the fraction of
      sludge in sediments. Of the PAHs, only naphthalene and methyl naphthalenes were
      detected in muscle, but did not display a dose-response. One bile metabolite of
      pyrene was quantified and demonstrates metabolism. Biota-sediment accumulation
      factors were of 0.2 to 7 indicating that equilibrium was approached, with the
      exception of the hepta and octachloro dioxins and furans which were not
      significantly bioaccumulated.

PMID- 10901668
TI  - Baseline concentrations of elements in the Antarctic macrolichen Umbilicaria
      decussata
AB  - Total concentrations of major and trace elements were determined in samples of
      the epilithic lichen Umbilicaria decussata from 24 ice-free areas in coastal
      Victoria Land (Antarctica). Overall average concentrations of trace elements
      except Cd were the lowest ever reported for lichens of the genus Umbilicaria.
      Specifically, the mean level of Pb in lichens from granitic rocks (0.46 +/- 0.18
      microg g(-1) dry wt) was more than four times lower than the lowest record in
      Arctic lichens. No impact of local human activities was detected, but the
      elemental composition of U. decussata was affected by entrapment of soil or rock
      dust particles and probably by uptake of soluble elements from substrate.
      Relationships between elements and their distribution patterns in the study area
      indicated that the marine environment is the main source of major ions and
      perhaps of Cd in lichens. Accumulation of P was detected in samples from coastal
      sites frequented by seabirds. Although the present results can be taken as
      baseline levels of major and trace elements in Antarctic U. decussata from
      substrates with very different geochemical features, further research is
      necessary to evaluate the relative element contribution from each substrate with
      respect to those from snow, marine aerosol, salt encrustations and guano.

PMID- 10901670
TI  - 2,3,7,8-Substituted PCDDs and PCDFs in sea lion (Otaria flavescens) skin biopsies
      from two South-western Atlantic populations.
AB  - Congener specific 2,3,7,8-chlorinated PCDDs and PCDFs were determined in skin
      biopsies taken from sea lions (Otaria flavescens) living in two areas of the
      South-western Atlantic on the coast of Argentina (Mar del Plata and Punta
      Bermeja). This is the first report on PCDDs and PCDFs in sea lion skin biopsies
      from the southern hemisphere. Differences were found in the congener pattern
      according to the sampling area. Animals living in the polluted area (Mar del
      Plata harbour) had detectable levels of all seventeen 2,3,7,8-substituted
      congeners. Sea lions living in a control environment (Punta Bermeja, Patagonia)
      only exhibited 5 detectable congeners out of all seventeen 2,3,7,8-substituted
      congeners. However, total levels were low in both colonies studied. These data
      are consistent with previous work which has indicated that dioxins occur at
      relatively low levels in marine mammals, possibly due to rapid catabolism or
      elimination.

PMID- 10901671
TI  - High Pressure Size Exclusion Chromatography (HPSEC) of humic substances:
      molecular sizes, analytical parameters, and column performance
AB  - High Pressure Size Exclusion chromatography (HPSEC) is increasingly used to
      evaluate molecular sizes of humic substances from different sources. Asymmetry
      factors (As), number of theoretical plates (N), coefficient of distribution
      (k(d)), and column resolution (Rs) were determined for two different HPSEC
      columns (TSK G3000SW and Biosep S2000) and polysaccharides of known molecular
      weights were used as standards. Calibration curves were equivalent for both
      columns whereas analytical parameters revealed that the TSK column was only
      slightly more efficient in separating polysaccharide standards. Mw and Mn values
      for humic substances differed according to the molecular weight range of each
      column but relative standard deviation never exceeded 5% for both columns.
      Variations between columns were attributed to intrinsic humic properties such as
      the stability of conformational structures. These results suggested that humic
      substances in solutions are loosely-bound association of small molecules that may
      be consistently dispersed by diffusion through size-exclusion pores. HPSEC is
      confirmed to represent a highly precise method to evaluate the relative molecular
      size distribution of dissolved humic substances.

PMID- 10901669
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin or 2,2',4,4',5,5'
      hexachlorobiphenyl on vitamin K-dependent blood coagulation in male and female
      WAG/Rij-rats.
AB  - Newborns are susceptible to hemorrhages (hemorrhagic disease of the newborn or
      HDN) due to vitamin K deficiency. Induction of cytochrome P450 in the fetal liver
      by maternal anticonvulsant therapy such as phenobarbital or phenytoin is
      considered to be a major cause. An observed increase in late hemorrhagic disease
      (LHD) in breast fed neonates gave rise to the hypothesis that PCBs and dioxins,
      P450-inducing contaminants present in human milk, might effect vitamin K
      dependent blood coagulation. This hypothesis was studied in rats. Administration
      of a single oral dose of 0.003, 0.03, 0.3, 3 or 30 nmol 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) per kg bodyweight or 0.75, 4, 20, 100 or 500
      micromol 2,2',4,4',5,5'-hexachlorobiphenyl/kg bw (HxCB) to female and male rats
      resulted in dose-related reductions of the vitamin K-dependent coagulation factor
      VII. The highest factor VII reduction in female rats was 44%, observed after TCDD
      exposure. The Lowest Observed Adverse Effect Level (LOAEL) of TCDD on female
      factor VII levels was 0.3 nmol/kg bw (96 ng/kg). There was a significant inverse
      correlation between Factor VII levels and induction of hepatic ethoxyresorufin O
      deethylating (EROD) activity, reflecting CYP1A1, and total P450 content. HxCB had
      no effect on female coagulation factors. In contrast, in male rats only exposure
      to HxCB, which induces mainly CYP2B1 and 2B2, decreased both coagulation factors
      dramatically up to 88%. The LOAEL of HxCB on factor VII in male rats was 100
      micromol/kg bw (36 mg/kg). In general, effects on coagulation factors in male
      rats exceeded those in females. In addition, sex-dependent differences of TCDD
      and HxCB were observed on the hepatic vitamin K cycle enzyme activities in female
      and male rats. Vitamin K-dependent (gamma-glutamyl carboxylase activity was
      mainly induced in female rats; 2.3-fold in the highest dose group of TCDD. In
      male rats only vitamin K 2,3-epoxide reductase (KO-reductase) activity was
      induced 1.7-fold by the highest dose of HxCB. KO-reductase activity in female
      rats was also increased by TCDD, however, less pronounced than the carboxylase
      activity. Concluding, the hepatic vitamin K cycle still functions and is not
      blocked by TCDD or HxCB, thus explaining the observed reduction in factor VII.
      Finally, the possible role of P450 in vitamin K deficiency is discussed. Based on
      these results it is suggested to investigate the possible role of PCBs and dioxin
      like compounds in LHD in more detail.

PMID- 10901672
TI  - Mechanism of the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans
      from chlorophenols in gas phase reactions
AB  - The pyrolysis of chlorinated phenates at a temperature of about 280 degrees C
      results in the formation of definite chlorinated dibenzodioxin (PCDD) congeners
      [1-3]. It is shown that in gas phase reactions chlorophenols react in the
      presence of oxygen above 340 degrees C not only to PCDD but also to chlorinated
      dibenzofurans (PCDF). The mechanism of this reaction of chlorophenols to PCDD and
      PCDF was elucidated. In a first step phenoxyradicals are formed which are capable
      of forming PCDDs and PCDFs. This is confirmed by the oxygen dependency of the
      reaction. In an argon atmosphere no dimerization of chlorophenols could be
      observed at 420 degrees C. By the identification of intermediates and by
      analyzing the PCDF isomers formed from individual chlorophenols the reaction
      pathway is elucidated. As intermediates in the formation of PCDFs polychlorinated
      dihydroxybiphenyls (DOHB) were identified. These are most likely formed by the
      dimerization of two phenoxy radicals at the hydrogen substituted carbons in ortho
      positions under simultaneous movement of the hydrogen atoms to the phenolic
      oxygen PCDDs are formed in the gas phase via ortho-phenoxyphenols (POP) analogous
      to the pyrolysis of phenates, but due to the radical mechanism in the first
      condensation step to POPs not only a chlorine atom is capable for substitution
      but also the hydrogen atoms. The formation of the DOHBs and their condensation to
      PCDFs and hydroxylated PCDFs as well as the ratio of PCDD to PCDF formed show a
      strong dependency on the reaction temperature, the substitution pattern of the
      chlorophenols and the oxygen concentration.

PMID- 10901673
TI  - Mass balance of trichloroacetic acid in the soil top layer
AB  - Since the ban on the use of trichloroacetic acid (TCAA) as a herbicide in several
      countries, TCAA is still found ubiquitously in the environment. The presence of
      TCAA nowadays is suggested to originate mainly from the atmospheric degradation
      of tetrachloroethene. Our mass balance calculations indicate that this may be
      true for the presence of TCAA in the atmosphere. However, our mass balance
      calculations also provide tentative evidence for the formation of TCAA in soil.
      If our calculated production fluxes are realistic estimates, a very large source
      of TCAA in soil has been identified.

PMID- 10901674
TI  - Reducing degradation of azo dye by zero-valent iron in aqueous solution
AB  - The reducing degradation kinetics of five azo dyes, Acid orange II, Acid orange
      IV, Acid orange GG, Acid red 3B and Orange I, by zero-valent iron powder in
      aqueous solution were studied. It showed that the degradation is a two-step
      reaction, with the first step being reversible. Solution acidity and iron surface
      area are the factors greatly influencing the degradation rates, and with
      increasing of acidity and iron surface area, the degradation rates increase.

PMID- 10901675
TI  - Vapour pressures, aqueous solubilities, Henry's law constants, partition
      coefficients between gas/water (Kgw), n-octanol/water (Kow) and gas/n-octanol
      (Kgo) of 106 polychlorinated diphenyl ethers (PCDE)
AB  - Modelling the environmental fate of persistent organic pollutants like
      polychlorinated diphenyl ethers (PCDE) requires the knowledge of a number of
      fundamental physico-chemical properties of these compounds. We report here the
      physico-chemical properties of 106 PCDEs, which are over 50% of all possible
      congeners. Vapour pressures P(OL), water solubilities S(H2O), and n-octanol/water
      partition coefficients K(OW) were determined with chromatographic methods. With
      these experimental data the Henry's law constants H, gas/water K(GW) and gas/n
      octanol K(GO) partition coefficients were calculated. Vapour pressures and water
      solubilities and n-octanol/water partition coefficients of the PCDEs are close to
      those of similar groups of organochlorine compounds like polychlorinated
      biphenyls (PCBs) and dibenzofurans (PCDFs). A similar environmental fate can be
      predicted and was partially already been observed.

PMID- 10901676
TI  - Routine analysis of hydrocarbons, PCB and PAH in marine sediments using
      supercritical CO2 extraction
AB  - Automated Supercritical Fluid Extraction (SFE), using CO2, was tested and
      optimised for routine analysis of hydrocarbons (THC), polychlorinated biphenyls
      (PCB) and polycyclic aromatic hydrocarbons (PAH) in marine sediments. The aim of
      the exercise was to reduce the amount of solvents used and to reduce the manual
      handling time for each sample. The sediments contained elemental sulphur, which
      was removed during the extraction step using activated Cu. Similar recoveries and
      reproducibility where found for THC when conventional solvent extractions and SFE
      where compared. Modifying the CO2 with methanol was necessary to obtain
      extraction recoveries similar to conventional extraction methods for PCB and PAH.

PMID- 10901677
TI  - Transport of rimsulfuron and its metabolites in soil columns
AB  - This paper presents a study on degradation, sorption and transport of the
      sulfonylurea herbicide rimsulfuron and its major metabolites in alluvial soil
      columns. The formulation of rimsulfuron was found to strongly affect its
      degradability. Hydrolysis of pure rimsulfuron takes place rapidly in distilled
      water (t(1/2)=2.2 days) or indeed instantaneously in alkaline solution. The
      formulated rimsulfuron (Titus, 25% rimsulfuron, Du Pont De Nemours) is more
      persistent in alluvial soil suspensions (t(1/2)=7.5 days). The study of sorption
      of Titus and its two major metabolites (1 and 2) revealed that these three
      chemicals are potentially highly mobile in the studied soil: in suspension
      distribution coefficients of 0.0028, 0.125 and 0.149 cm3 g(-1) were obtained
      respectively. Given the instability of rimsulfuron in alkaline solutions, the pH
      effect was evaluated with metabolite 2 in water saturated Fontainebleau sand
      columns at pH 6, 8 and 10. Transport was found to be strongly dependent on pH; a
      linear relationship was obtained between pH and the retardation factor or the
      dispersion coefficient. In alluvial soil columns, rimsulfuron from Titus was
      found to be very mobile (R=1.2) and rapidly degraded into metabolites 1 and 2,
      which were transported at a similar velocity. Nevertheless, the risks of
      groundwater contamination by rimsulfuron seem very low, as it is rapidly degraded
      under dynamic conditions (t(1,2)=1.4 days). On the other hand the relatively
      stable metabolite 2 seems likely to persist in the soil and to be transported to
      the groundwater. Special attention should thus be given to this compound at least
      as long as its harmlessness is not demonstrated.

PMID- 10901678
TI  - Effect of adsorbents coated with titanium dioxide on the photocatalytic
      degradation of propoxur
AB  - Photocatalytic oxidation of pesticides in aqueous media irradiated by UV light is
      a rapidly growing field of research. Therefore, the treatment technology for
      degradation of propoxur (an insecticide) using titanium dioxide coated on the
      supports such as activated carbon, zeolite, brick, quartz and glass beads, was
      performed in this research. Results show that GAC/TiO2 is the best complexing
      agent for oxidizing propoxur because of its adsorption properities. The others
      follow the sequence: plain TiO2 > glass beads > zeolite > brick > quartz. The
      degradation rate of propoxur with plain TiO2 is higher than that with TiO2/GAC
      complexing agent. But the mineralization rate of propoxur with plain TiO2 is
      lower than that with TiO2/GAC complexing agent. However, it can be concluded that
      using GAC as the support can improve the photocatalytic efficiency.

PMID- 10901679
TI  - Qualitative determination of 10,10'-oxybisphenoxarsine and decabromodiphenyl
      ether in plastics.
AB  - Plastics destined for facilities holding aquatic fauna, such as aquaculture and
      aquatic toxicology laboratories, were studied. The plastics were extracted with
      dichloromethane. The fungicide 10,10'-oxybisphenoxarsine (OBPA) was detected by
      silver nitrate after cleanup on a silica cartridge and TLC in petroleum ether
      diethyl ether-acetic acid 80:20:1. The flame retardant decabromodiphenyl ether
      (DBDPO) was crystallized from dichloromethane and confirmed by IR spectrum. A UV
      spectrophotometric method is suggested for the estimation of the leaching
      potential of additives from plastics.

PMID- 10901681
TI  - The sorption of airborne pollutants on natural and synthetic surfaces:
      correlation to the mathematical models
AB  - The laboratory experiments were carried out to study the sorption process of
      gaseous toluene in the peel of different fruits as well as in the chemically
      prepared material based on silica support (multiligand-adsorbent). For the
      sorption experiments, a vapor generating system was used that allows the exposure
      of sorbents to a constant flux of polluted air. The concentration of toluene in
      the tested sorbents was followed as a function of exposure time. The obtained
      results were correlated to the mathematical models describing the sorption
      kinetics in the leaves. The investigation with the plant material showed dual
      phase behavior of the toluene partition ('mixed' sorption mechanism), in the case
      of multiligand-adsorbent a typical adsorption process was observed. Sorption
      kinetics to fruit material was well correlated to the two-compartment model,
      while for the chemically prepared material to the first-order model.

PMID- 10901682
TI  - Tolerance to trichlorophenols in microorganisms from a polluted and a pristine
      site of a river
AB  - The effect of 2,4,5- and 2,4,6-trichlorophenol on the microbiota from a polluted
      and a pristine site of a river was studied. Bacterial metabolic activity
      measurements by epifluorescence microscopy showed that the polluted site
      contained more metabolically active cells than the pristine site. Total
      culturable bacterial counts and tolerant bacterial counts from both sites were
      not affected by incubation (for up to 5 days) with 200 ppm of chlorophenols.
      However, the incubation with 500 ppm of 2,4,5-trichlorophenol prevented detection
      of total and tolerant bacterial counts in the pristine site, and inhibited
      tolerants in the polluted site. None of 250 bacterial colonies directly isolated
      from these samples was able to grow on chlorophenols. However, bacteria able to
      grow on 2,4,6-trichlorophenol, were obtained by enrichment of water and sediments
      samples.

PMID- 10901680
TI  - Specific detection of p-chlorobenzoic acid by Escherichia coli bearing a plasmid
      borne fcbA'::lux fusion.
AB  - In this communication we report on a genetically engineered bacterium that reacts
      by light emission to the presence of 4-chlorobenzoic acid. To construct this
      strain, DNA fragment (1.7 kb) upstream from the 4-chlorobenzoic acid dehalogenase
      (fcb) operon of Arthrobacter SU was fused to Vibriofischeri luxCDABE genes. An
      Escherichia coli strain transformed with a multi-copy plasmid (pASU) bearing this
      fusion responded to the presence of 4-chlorobenzoic acid and a few closely
      related compounds by increased luminescence, exhibiting a high specificity but a
      relatively low sensitivity. While it could be somewhat, improved by manipulating
      the experimental pH, sensitivity remained too low for real time applicability.
      Nevertheless, the principle of using dehalogenase promoters as environmental
      pollution sensor was demonstrated.

PMID- 10901683
TI  - Comparison of the characteristics of flow-through and flow-around leaching tests
      of Solidified heavy metal wastes
AB  - This paper introduces a research work on studying the possibility of using a flow
      through leaching test method to simulate the leaching behaviour of the cement
      based stabilized/solidified (S/S) hazardous wastes. Both the flow-through
      leaching and the more common flow-around (dynamic leaching) test methods were
      carried out in the study to compare the leaching behaviour of the solidified
      waste under different leaching environments. The solidified waste samples were
      prepared from five kinds of heavy metals with two kinds of binders. The metals
      were Pb2+, Zn2+, Cu2+, Ni2+ (positive ions as nitrate), and Cr6+ (as a negative
      ion in potassium dichromate), and the binders were type I Ordinary Portland
      Cement (OPC) and Pulverised Fuel Ash (PFA). The results of two series of flow
      through and flow-around leaching experiments are reported and compared in this
      paper. Mathematical models for simulating the leaching behaviour of the flow
      through and flow-around leaching conditions were used to determine the
      diffusivities of the contaminants. The results show that, since the matrix of the
      solid waste in a flow-through leaching test is always being degraded, the
      diffusivities continuously increased during the leaching period. The range of the
      diffusivities was 10E-8 to 10E-3 cm2/s, which corresponds to the case of liquid
      phase diffusion. But in the case of the flow-around (dynamic leaching) test, the
      range of the diffusivities was 10E-18 to 10E-9 cm2/s which was similar to solid
      phase diffusion, and the variation of the diffusivity with time was not regular.

PMID- 10901684
TI  - Quantification of organotin compounds and determination of imposex in populations
      of dogwhelks (Nucella lapillus) from Norway.
AB  - Unintentional effects of the antifouling agent tributyltin (TBT) have been
      discovered in marine gastropods as the induction of male sex characters in
      females, known as imposex. The occurrence of imposex in dogwhelks (Nucella
      lapillus) was investigated in 41 populations sampled in 1993-1995 along the
      Norwegian coast. A method for quantification of organotin species using gas
      chromatography and atomic emission detection (GC-AED) was developed. Some degree
      of imposex occurred in almost all populations of dogwhelks studied, except in
      four from Northern Norway. The concentration of organotin compounds in the
      gastropods from the unaffected populations was below the detection limit (7 ng
      Sn/g d.w.). The concentration of TBT in dogwhelks from affected populations was
      in the range 48-1096 ng Sn/g d.w. A positive relation between the concentration
      of TBT in dogwhelks and the degree of imposex was found.

PMID- 10901685
TI  - Incorporation of SPECT imaging in a longitudinal cognitive rehabilitation therapy
      programme.
AB  - In this clinical study, five consecutive referrals to a cognitive rehabilitation
      therapy (CRT) programme were followed in a longitudinal protocol involving a
      resting SPECT and neuropsychological evaluation at pre-treatment, post-treatment,
      and post non-treatment intervals. All clients had acquired brain injury and
      initially demonstrated neuropsychological deficits and various degrees of
      hypoperfusion on SPECT. Statistical Parametric Mapping (SPM) was used to evaluate
      change in successive SPECT images. Following CRT, all clients were able to return
      to productive employment or schooling. Examination of the neuropsychological
      testing results revealed significant improvement in performance following CRT
      which were generally maintained during the non-treatment period. SPM analysis of
      the SPECT data revealed that, in a majority of cases, most of the significant
      increases in relative cerebral blood flow redistribution were seen during the
      treatment period, rather than the non-treatment period. The results suggest that,
      even in individuals who are more than 2 years post-brain damage, relative
      increases in rCBF can be demonstrated following individualized CRT and that most
      of these changes can be related to improvements on neuropsychological tests.

PMID- 10901686
TI  - Pre-injury substance abuse among persons with brain injury and persons with
      spinal cord injury.
AB  - Alcohol and drug use at the time of injury have been strongly implicated as
      causal factors of spinal cord injury (SCI) and traumatic brain injury (TBI).
      Researchers have only begun their efforts to investigate the pre-injury incidence
      of substance abuse in an effort to identify persons at risk for traumatic injury.
      No studies have compared brain and spinal cord injury populations. This
      investigation was based in an urban, level one trauma center federally designated
      as a model system of comprehensive rehabilitative services for persons with TBI
      and persons with SCI. Pre-injury patterns of alcohol and illicit drug use were
      compared among patients with SCI and patients with TBI, matched for age, gender,
      race, and mechanism of injury (n= 52). In accordance with previous research,
      participants were primarily young, unmarried, males with at least a high school
      education. Eighty-one percent of patients with TBI and 96% of patients with SCI
      reported pre-injury alcohol use. The rate of pre-injury heavy drinking for both
      groups was alarmingly high. Fifty-seven percent of persons with SCI and 42% of
      persons with TBI were heavy drinkers. Implications for risk identification,
      treatment, and future research are discussed.

PMID- 10901687
TI  - The 'preliminary neuropsychological battery'. An instrument to grade the
      cognitive level of minimally responsive patients.
AB  - An early, formalized cognitive evaluation of'minimally responsive' patients could
      be important in the planning of their care and rehabilitation as well as in
      providing a realistic prognosis and studying the modality of the cognitive
      recovery. A short, bedside, neuropsychologically-oriented test-battery, the
      Preliminary Neuropsychological Battery, a psychometric tool which enables the
      cognitive evaluation of these patients and of patients unable to give verbal or
      complex motor answers, has been devised. The BNP was administered to a sample of
      40 head-injured patients and to a sample of 34 healthy subjects. The aim was (i)
      to evaluate its usefulness, and (ii) to study its correlation with cortical
      functions as assessed by a more extensive battery. The findings suggest that the
      BNP is useful for assessing the general cognitive level of head-injured post
      comatose patients. It was able to detect patients deserving a wider, analytic,
      neuropsychological assessment. Attentional defects emerged as an important
      variable determining the BNP score.

PMID- 10901688
TI  - Relationship and family breakdown following acquired brain injury: the role of
      the rehabilitation team.
AB  - Although the literature documents the considerable problems acquired brain injury
      causes for the survivor's family and close relationships, and the corresponding
      significantly inflated rate of separation and divorce, few papers offer practical
      solutions. The objective of this paper is to respond to this gap in the
      literature by presenting some of the problems raised for the rehabilitation team
      when a family separates, and some suggestions for ways in which these problems
      could be overcome. The literature is reviewed briefly, followed by reflections
      and suggestions which are based on this review and on clinical experience. The
      discussion indicates that there are a number of practical dilemmas raised for the
      rehabilitation team when a family already involved in the rehabilitation process
      starts to break up. Some specific suggestions for addressing these issues are
      made; further research is needed to evaluate their effectiveness.

PMID- 10901689
TI  - Memory remediation in long-term acquired brain injury: two approaches in diary
      training.
AB  - This study investigated the remediation and assessment of everyday memory
      impairment in a sample of long-term acquired brain injury (ABI) subjects. The
      Rivermead Behavioural Memory Test (RBMT) and subtests of the Wechsler Memory
      Scale-Revised (WMS-R) were selected to measure global memory performance. A
      memory questionnaire and a daily memory checklist were developed from a review of
      existing self-report questionnaires. The interrelationships among self-report
      measures and standardized psychometric tests of memory were examined and the
      findings suggest that self-report measures may be used to obtain relatively
      accurate information about everyday memory performance. A baseline across groups'
      design evaluated the relative effectiveness of two different approaches in
      training subjects to use a diary to compensate for memory problems. There was a
      Diary Only (DO) approach, which emphasized compensation based upon task specific
      learning, and a Diary and Self-Instructional Training (DSIT) approach, which
      taught compensation using higher cognitive skills of self-awareness and self
      regulation. The results obtained show that, during the treatment phase, the DSIT
      group more consistently made diary entries, reported less memory problems, and
      made more positive ratings associated with treatment efficacy. The implications
      arising from the current study are that: (1) the choice of memory assessment
      procedures need to be guided by the patients' real daily living needs; and (2) an
      approach based upon self-instructional training has greater ecological validity
      than an approach that focuses on task specific learning. In general, successful
      assessment and rehabilitation of memory deficits requires a well-established
      theoretical basis and sound ecological validity.

PMID- 10901690
TI  - A comparison of traumatic brain injury in the Saskatchewan native North American
      and non-native North American populations.
AB  - OBJECTIVE: To compare native North American and non-native North American
      patients admitted for inpatient rehabilitation following traumatic brain injury
      in order to identify pertinent differences between the two groups with regards to
      the initial injury, medical management and allocated resources. DESIGN: A
      retrospective chart review was performed on all patients admitted to the unit
      between July 1994 and March 1997 with the diagnosis of traumatic brain injury.
      RESULTS: Significant differences were found between the two groups in the areas
      of alcohol and drug involvement with the initial injury (p < 0.0001),
      geographical location of the injury (p < 0.0001), initial treatment received (p =
      0.0102), discharge planning (p < 0.0001), and post-discharge follow-up (p =
      0.0052). CONCLUSIONS: The results indicate that native North Americans are more
      likely to suffer a head injury than non-native North Americans, that alcohol is
      more likely to be involved, and that native North American patients are less
      likely to be offered post-discharge resources. Further prospective study to
      explore these areas is required.

PMID- 10901691
TI  - Moclobemide in the treatment of major depressive disorder (DSM-3) following
      traumatic brain injury.
AB  - Major depression (MDD) following traumatic brain injury (TBI) is a common
      phenomenon. There are no adequate studies in the literature defining optimum
      treatments for this condition following TBI. The opportunity arose to analyse a
      group of patients who were included in a larger study of an antidepressant
      (moclobemide). As the treatment, but not the delivery, was known, this has the
      status of an open study. Twenty-six patients with major depression of late onset
      (mean 4.67 years post-TBI) were identified (18 male, 8 female), with a mean age
      at injury 28.49 years. The group was moderately depressed with Hamilton
      Depression score (HAM-D) of 23.385 and moderately anxious with Hamilton Anxiety
      score (HAM-A) of 21.231. Mean HAM-D reduction was 81% and HAM-A reduction 81%. Of
      the 26 subjects 23 were defined as responders. Onset of action was rapid, with 17
      responding by day 3. Irritability scores showed a mean reduction of 57% and pain
      scores a reduction of 39%. It is concluded that moclobemide may be an effective
      treatment for MDD following TBI, but properly controlled studies must be carried
      out to confirm this.

PMID- 10901692
TI  - CYP2C8/9 mediate dapsone N-hydroxylation at clinical concentrations of dapsone.
AB  - Using selective cytochrome P450 (CYP) inhibitors and clinical concentrations (4
      microM) of dapsone (DDS), we found a major contribution of CYP2C9 and little or
      no contribution (< or = 10%) of CYP3A4 and CYP2E1 to dapsone N-hydroxylation (DDS
      NHY) in human liver microsomes. Sulfaphenazole (2.16 microM) and tolbutamide (500
      microM), selective inhibitors of CYP2C9 (or 2C8/9), inhibited DDS-NHY by 48 +/-
      14 and 41 +/- 15%, respectively. The apparent Michaelis-Menten Km values for DDS
      NHY by cloned CYP2C8, CYP2C9, CYP2C18, and CYP2C19 were 75 microM, 31 microM, 25
      microM, and greater than 1 mM, respectively. CYP3A4 and CYP2E1 were incapable of
      DDS-NHY at 4 microM DDS. S-mephenytoin (360 microM) activated DDS-NHY by human
      liver microsomes and by CYP2C8 by 43 +/- 36 and 193 +/- 16%, respectively. This
      activation was cytochrome b5-dependent. In contrast, S-mephenytoin inhibited DDS
      NHY by CYP2C9, CYP2C18, and CYP2C19 by 27 +/- 2, 49 +/- 1, and 32 +/- 4%,
      respectively. Because CYP2C18 and CYP19 are expressed at low concentrations in
      the human liver, these observations indicate that at clinical DDS concentrations,
      CYP2C9 is a major and CYP2C8 is a likely minor contributor to DDS-NHY in human
      liver microsomes.

PMID- 10901693
TI  - Comparative N-glucuronidation kinetics of ketotifen and amitriptyline by
      expressed human UDP-glucuronosyltransferases and liver microsomes.
AB  - Like other basic amphiphilic drugs, the (S)-enantiomer of the antiallergic drug
      ketotifen exhibited biphasic kinetics when it was converted to two isomeric
      quaternary ammonium-linked glucuronides in human liver microsomes. For (R)
      ketotifen this applied when incubations were carried out in the absence of a
      detergent. Two UDP-glucuronosyltransferases (UGTs) present in human liver, UGT1A4
      and UGT1A3, were previously shown to catalyze tertiary amine N-glucuronidation
      when expressed in HK293 cells. Therefore, the conjugation kinetics of (R)- and
      (S)-ketotifen were investigated with the two expressed proteins. When homogenates
      of HK293 cells expressing UGT1A4 were incubated without detergent, N
      glucuronidation kinetics were monophasic with K(M) values of 59 +/- 5 microM for
      (R)- and 86 +/- 26 microM for (S)-ketotifen. In experiments with membranes
      containing expressed UGT1A3, somewhat higher K(M) values were obtained. These
      values correspond to the high rather than to the low K(M) components of ketotifen
      glucuronidation in liver microsomes, the latter exhibiting K(M) values around 2
      and 1 microM, respectively, with (R)- and (S)-ketotifen. With amitriptyline as
      the substrate, N-glucuronidation kinetics in the absence of detergent were
      biphasic in human liver microsomes and monophasic with a high K(M) value in cell
      homogenates containing UGT1A4. The results suggest that UGT1A4 and UGT1A3
      catalyze high-K(M) N-glucuronidation of tertiary amine drugs, whereas the low
      K(M) reaction requires either an alternative enzyme or a special conformation of
      UGT1A4 or UGT1A3 that can be attained in liver microsomes, but not in HK293 cell
      membranes.

PMID- 10901694
TI  - Biliary and urinary metabolic profiles of 1,2-diethyl-3-hydroxypyridin-4-one
      (CP94) in the rat.
AB  - This study compares the biliary and urinary metabolic profiles of 1,2-diethyl-3
      hydroxypyridin-4-one (CP94), an orally active iron chelator, in the normal rat.
      Surprisingly, CP94 was found to form two phase II metabolites, the 3-O- and 4-O
      glucuronides. These glucuronides accounted for 38 and 28% of the administered
      CP94 dose, in bile and urine, respectively. Unchanged CP94 accounted for 5% of
      the CP94 dose in both bile and urine. The 2-(1'-hydroxy) metabolite of CP94 was
      found to be the dominant metabolite in urine. In addition, an unstable metabolite
      was detected in the bile although its structure remains unknown at the present
      stage. The excretion of iron in bile, after administration of CP94, was found to
      parallel the biliary elimination of CP94 together with its hydroxylated
      derivatives, indicating the importance of metabolites in iron excretion.

PMID- 10901695
TI  - Metabolism of para-aminophenol by rat hepatocytes.
AB  - Autoxidation of para-aminophenol (PAP) has been proposed to account for the
      selective nephrotoxicity of this compound. However, other studies suggest that
      hepatic metabolites of PAP rather than the parent compound may be responsible for
      renal damage. These studies were designed to investigate PAP metabolism in
      isolated hepatocytes. We synthesized several proposed metabolites for analysis by
      HPLC/mass spectrometry and compared those results with HPLC/mass spectrometric
      analyses of metabolites found after incubating hepatocytes with PAP. Hepatocytes
      prepared from male Sprague-Dawley rats were incubated in Krebs-Henseleit buffer
      at 37 degrees C for 5 h with 2.3 mM PAP under an atmosphere of 5% CO2/95% O2.
      Aliquots were withdrawn at 0.1 h of incubation and then hourly through 5 h of
      incubation. Reactions were terminated by the addition of acetonitrile. Hepatocyte
      viability was unaltered with PAP present in the incubation medium. We found that
      hepatocytes converted PAP to two major metabolites (PAP-GSH conjugates and PAP-N
      acetylcysteine conjugates) and several minor metabolites [PAP-O-glucuronide,
      acetaminophen (APAP), APAP-O-glucuronide, APAP-GSH conjugates, and 4
      hydroxyformanilide]. Preincubating hepatoyctes with 1-aminobenzotriazole, an
      inhibitor of cytochromes P450, did not alter the pattern of PAP metabolism. In
      conclusion, we found that PAP was metabolized in hepatocytes predominantly to PAP
      GSH conjugates and PAP-N-acetylcysteine conjugates in sufficient quantities to
      account for the nephrotoxicity of PAP.

PMID- 10901696
TI  - Oxidative cleavage of the octyl side chain of 1-(3,4-dichlorobenzyl)-5
      octylbiguanide (OPB-2045) in rat and dog liver preparations.
AB  - The metabolism of 1-(3,4-dichlorobenzyl)-5-octylbiguanide (OPB-2045), a new
      potent biguanide antiseptic, was investigated using rat and dog liver
      preparations to elucidate the mechanism of OPB-2045 metabolite formation, in
      which the octyl side chain is reduced to four, five, or six carbon atoms.
      Chemical structures of metabolites were characterized by 1H NMR, fast atom
      bombardment/mass spectrometry, and liquid chromatography/electrospray ionization
      tandem mass spectrometry. Three main metabolites were observed during incubation
      of OPB-2045 with rat liver S9: 2-octanol (M-1), 3-octanol (M-2), and 4-octanol (M
      3). In the incubation of OPB-2045 with dog liver S9, eight metabolites were
      observed, seven of which being M-1, M-2, M-3, 2-octanone (M-4), threo-2,3
      octandiol (M-5), erythro-2,3-octandiol (M-6), and 1,2-octandiol (M-7). M-5 and M
      6 were further biotransformed to a ketol derivative and C-C bond cleavage
      metabolite (hexanoic acid derivative), an in vivo end product, in the incubation
      with dog liver microsomes. The reactions required NADPH as a cofactor and were
      significantly inhibited by the various inhibitors of cytochrome P450 (i.e., CO, n
      octylamine, SKF 525-A, metyrapone, and alpha-naphthoflavone). The results
      indicate that the degraded products of OPB-2045 are produced by C-C bond cleavage
      after monohydroxylation, dihydroxylation, and ketol formation at the site of the
      octyl side chain with possible involvement of cytochrome P450 systems. This
      aliphatic C-C bond cleavage by sequential oxidative reactions may play an
      important role in the metabolism of other drugs or endogenous compounds that
      possess aliphatic chains.

PMID- 10901697
TI  - Mibefradil is a P-glycoprotein substrate and a potent inhibitor of both P
      glycoprotein and CYP3A in vitro.
AB  - Mibefradil, a calcium T- and L-channel blocker developed for use in hypertension,
      was recently removed from the market after reports of severe drug-drug
      interactions. Mibefradil is known to inhibit various cytochrome P450 enzymes
      involved in drug metabolism, particularly CYP3A. However, the extent and the
      severity of the observed drug interactions in humans suggest that inhibition of
      additional systems important to drug disposition, such as the drug transporter P
      glycoprotein (P-gp), may also have contributed to the severity of the mibefradil
      interactions. A polarized epithelial cell line, LLC-PK1, which does not express P
      gp, and the derived L-MDR1 cell line, which overexpresses human P-gp, were used
      to study the effects of mibefradil on drug transport. A markedly greater basal-to
      apical versus apical-to-basal transport of [H3]mibefradil was seen in the L-MDR1,
      but not in the LLC-PK1 cells, suggesting that the drug is a substrate of P-gp.
      Using a human intestinal cancer-derived cell line Caco-2, which constitutively
      expresses P-gp, mibefradil was shown to be a potent inhibitor of P-gp-mediated
      digoxin transport, with an IC50 of 1.6 microM. Additionally, the effect of
      mibefradil on CYP3A was assessed using human liver microsomes. Mibefradil
      inhibited CYP3A-mediated nifedipine oxidase activity with an IC50 of 0.8 microM,
      and a Ki of 0.6 microM. Thus, mibefradil is not only a P-gp substrate, but also a
      potent inhibitor of both P-gp and CYP3A. These data suggest that the severity of
      drug interactions seen with mibefradil use is due to the dual inhibition of both
      P-gp and CYP3A.

PMID- 10901698
TI  - Isolation and identification of urinary metabolites of porfiromycin in dogs and
      humans.
AB  - Porfiromycin (PM), a bioreductive alkylating agent, is currently under
      development for the treatment of head and neck cancers as an adjunct to radiation
      therapy in phase III clinical trials. After i.v. administration of a single dose
      of PM to patients at 40 mg/m2, urinary metabolites were isolated by HPLC and
      identified by atmospheric pressure chemical ionization mass spectrometry. In
      dogs, [methyl-3H]PM was administered i.v. to three Beagle dogs at a single dose
      of 2 mg/kg. Urinary excretion of radioactivity and PM at different times was
      determined by liquid scintillation counting and by HPLC, respectively. An average
      of 48.0% of total radioactivity given to the dogs was cumulatively excreted in
      urine over a period of 7 days. Unchanged parent drug excreted in urine accounted
      for 10.8% of the administered dose over the same period of time. The results
      indicated that the majority of excreted dose in dog urine was in the form of
      metabolites. Three phase I and four phase II metabolites of PM were identified in
      human and dog urine. The phase I metabolites are 2-methylamino-7-aminomitosene,
      1,2-cis and 1,2-trans-1-hydroxy-2-methylamino-7-aminomitosenes. The phase II
      metabolites are a pair of isomeric N-acetylcysteine S-conjugates and a pair of
      isomeric cysteine S-conjugates of mitosenes at the C-1 and C-10 positions. Most
      of the identified metabolites were confirmed by comparison with synthetic
      reference standards using HPLC and liquid chromatography/mass spectrometry
      (LC/MS). The identification of mercapturic acids and cysteine S-conjugates in
      urine indicates that the metabolism of PM may be through GSH conjugation.

PMID- 10901700
TI  - Ontogeny of valproic acid disposition and metabolism: a developmental study in
      postnatal lambs and adult sheep.
AB  - The ontogeny of valproic acid (VPA) disposition and metabolism was investigated
      in developing lambs and adult sheep (Dorset or Suffolk breed). Specifically, we
      wished to investigate the role of glucuronidation and beta-oxidation on VPA
      elimination during development. Catheters were implanted in a carotid artery, a
      jugular vein, and the urinary bladder in 10-day-old (10 d; n = 8), 1-month-old (1
      M; n = 4), and 2-month-old lambs (2 M; n = 5). In adult sheep (n = 5), catheters
      were implanted in a femoral artery and vein. After the administration of a 10
      mg/kg VPA i.v. bolus, serial blood samples and cumulative urine samples were
      collected for 36 h in the adult ewes and for 72 h in the lambs. Due to saturable
      protein binding, age-related differences in VPA clearance were more obvious when
      examining the total body clearance of unbound drug (Cl(u)tb). Mean Cl(u)tb
      increased significantly with age up to 2 months (10 d = 2.65 +/- 1.16 ml/min/kg;
      1 M = 5.11 +/- 2.49 ml/min/kg; 2 M = 12.84 +/- 3.88 ml/min/kg) before decreasing
      to adult levels (7.73 +/- 2.64 ml/min/kg). Similarly, the urinary recovery of the
      major metabolite, VPA-glucuronide, was significantly less in 10 d lambs (29.2 +/-
      16.0% of the dose) when compared with the adult and 2 M groups (both
      approximately 74% of the dose). No differences with age were observed in the
      portion of the dose excreted as the beta-oxidation metabolite, 2-n-propyl-3
      oxopentanoic acid. The results suggest that alterations in Cl(u)tb with age may
      be attributable to postnatal development of enzymes involved in VPA
      glucuronidation.

PMID- 10901701
TI  - Assessment of the metabolic chiral inversion of D-leucine in rat by gas
      chromatography-mass spectrometry combined with a stable isotope dilution
      analysis.
AB  - The stereoselective pharmacokinetics of leucine enantiomers in rats has been
      investigated to evaluate the inversion of D-leucine to L-enantiomer. After a
      bolus i.v. administration of D- or L-[2H7]leucine to rats, blood samples were
      obtained over 6 h after administration and analyzed by a stereoselective gas
      chromatography-mass spectrometry method. Racemic [2H3]leucine was used as an
      internal standard. The method involved methyl esterification and subsequent
      chiral derivatization with (+)-alpha-methoxy-alpha-trifluoromethylphenylacetyl
      chloride to form the diastereomeric amide. The derivatization made possible the
      separation of leucine enantiomers with good gas chromatographic behavior. Plasma
      concentration of both D- and L-[2H7]leucine declined biexponentially, with
      elimination half-lives of 60 and 14 min, respectively. In contrast to the L
      enantiomer, the D-enantiomer had a lower systemic clearance. When D-[2H7]leucine
      was administered, the L-enantiomer was found to rapidly appear in plasma. About
      30% of an administered dose of the D-isomer was stereospecifically inverted to
      the L-enantiomer. There was no measurable inversion of the L- to D-enantiomer.
      This methodology has made it possible to evaluate the pharmacokinetics of each
      enantiomer of amino acids and estimate of chiral inversion after administration
      of D-amino acids.

PMID- 10901699
TI  - Mechanism-based inactivation of cytochromes P450 2B1 and P450 2B6 by 2-phenyl-2
      (1-piperidinyl)propane.
AB  - 2-Phenyl-2-(1-piperidinyl)propane (PPP), an analog of phencyclidine, was tested
      for its ability to inactivate cytochrome P450s (P450s) 2B1 and 2B6. PPP
      inactivated the 7-(benzyloxy)resorufin O-dealkylation activity of liver
      microsomes obtained from phenobarbital-induced rats with a K(I) of 11 microM. The
      7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity of purified rat
      liver P450 2B1 and expressed human P450 2B6 was inactivated by PPP in a
      reconstituted system containing NADPH-cytochrome P450 reductase and lipid. In the
      presence of NADPH, the loss of activity was time- and concentration-dependent,
      and followed pseudo first order kinetics. The rate of inactivation for P450 2B1
      was 0.3 min(-1), and the concentration of PPP required to achieve half-maximal
      inactivation was 12 microM. The time for 50% of the P450 2B1 to become
      inactivated at saturating concentrations of PPP was 2.5 min. P450 2B6 was
      inactivated with a k(inact) of 0.07 min(-1), a K(I) of 1.2 microM, and a t(1/2)
      of 9.5 min. The inactivated P450s 2B1 and 2B6 lost about 25 and 15%,
      respectively, of their ability to form a CO-reduced complex, suggesting that the
      loss of activity was caused by a PPP modification of the apoprotein rather than
      the heme. The estimated partition ratio for P450s 2B1 and 2B6 with PPP was 31 and
      15, respectively. The inactivation was not reversible and reductase activity was
      not affected. Coincubation of P450 2B1 and 2B6 with PPP and NADPH in the presence
      of an alternate substrate protected both enzymes from inactivation. The exogenous
      nucleophile GSH did not affect the rate of inactivation. PPP-inactivated P450s
      2B1 and 2B6 were recognized on Western blots by an antibody generated to
      phencyclidine that had been conjugated to BSA. Stoichiometries of 1.4:1 and 0.7:1
      were determined for the binding of a [3H]PPP metabolite to P450 2B1 and 2B6,
      respectively.

PMID- 10901702
TI  - Pharmacokinetic profiles in rats after intravenous, oral, or dermal
      administration of dapsone.
AB  - Dapsone is a potent anti-inflammatory and antibacterial agent that has been used
      extensively in the oral treatment of leprosy and dermatitis herpetiformis. This
      study compared the pharmacokinetic profile of dapsone in rats given a single oral
      or i.v. 12 mg/kg dose (n = 8/group) or a single dermal application of 12 or 60
      mg/kg (n = 12/group) in an aqueous gel application medium containing 10 or 25%
      diethylene glycol monoethyl ether (DGME). Blood samples (200 microl) were
      collected via tail vein from each rat and pooled at intervals up to the 24-h
      period. A terminal blood sample was collected by cardiac puncture from each
      animal. Plasma concentrations of dapsone were determined by liquid chromatography
      atmospheric pressure ionization tandem mass spectroscopy. There was no treatment
      related overt toxicity observed in any of the animals. Peak levels were reached 1
      h after oral dosing (4890 ng/ml), and 6 to 8 h after dermal application, with
      Cmax values of 1.62, 5.56, and 12.8 ng/ml, for 12 mg/kg at 10 or 25% DGME, and
      for 60 mg/kg at 25% DGME, respectively. Bioavailability was calculated at 78%
      after oral dosing and <1% after dermal application. Apparent elimination half
      lives (t(1/2))s were similar after i.v. and oral dosing. Both the calculated area
      under the plasma concentration versus time curve up to 24 h and Cmax values were
      3- to 4-fold higher in the dermal application group administered 12 mg/kg dapsone
      in 25 versus 10% DGME gel, whereas the calculated area under the plasma
      concentration versus time curve up to 24 h and Cmax values for the 60 mg/kg group
      were only 3.3- and 2.3-fold greater than those obtained after application of 12
      mg/kg in 25% DGME. These results show that both systemic exposure and peak plasma
      concentrations of dapsone are minimized by dermal versus oral administration of
      the compound.

PMID- 10901703
TI  - Concurrent flavin-containing monooxygenase down-regulation and cytochrome P-450
      induction by dietary indoles in rat: implications for drug-drug interaction.
AB  - Our laboratory has previously shown that dietary administration of indole-3
      carbinol (I3C) to male Fischer 344 rats has the very unusual property of inducing
      hepatic levels of a number of cytochrome P450s (CYPs), especially CYP1A1, while
      markedly inhibiting the levels of flavin-containing monooxygenase (FMO) 1 protein
      and its catalytic activity. We hypothesized that rats fed I3C or 3,3'
      diindolylmethane (DIM), one of its major acid condensation products formed in
      vivo, should exhibit a marked shift in the metabolic profiles of drugs or
      xenobiotics that are substrates for both monooxygenase systems. Male rats were
      fed AIN-76A powdered diets containing 0, 1000, or 2500 ppm I3C or DIM for 4
      weeks. Dietary I3C and DIM reduced FMO1 protein levels (8% reduction with I3C and
      84% with DIM at 1000 ppm, and 90% reduction with I3C and 97% with DIM at 2500
      ppm) in hepatic microsomes. The ratio of FMO (N-oxygenation)- to CYP (N
      demethylation)-mediated metabolism of N,N-dimethylaniline decreased in liver
      microsomes from I3C- or DIM-fed rats from near unity to 0.02 at the highest
      dietary doses. FMO-mediated N-oxygenation (nicotine N-1'-oxide) was decreased,
      whereas CYP-mediated (nornicotine and nicotine delta (1,5)-iminium ion)
      metabolism of nicotine was unchanged in liver microsomes from rats fed I3C or
      DIM. Similarly, the ratio of FMO to CYP metabolites of tamoxifen decreased due to
      a reduction in N-oxygenation. This study demonstrates alteration of FMO- and CYP
      mediated drug metabolism in vitro by dietary I3C or DIM and suggests the
      potential for altered toxicity of tamoxifen and nicotine in vivo.

PMID- 10901704
TI  - Identification of CYP3A4 as the enzyme involved in the mono-N-dealkylation of
      disopyramide enantiomers in humans.
AB  - To identify which cytochrome P-450 (CYP) isoform(s) are involved in the major
      pathway of disopyramide (DP) enantiomers metabolism in humans, the in vitro
      formation of mono-N-desalkyldisopyramide from each DP enantiomer was studied with
      human liver microsomes and nine recombinant human CYPs. Substrate inhibition
      showed that SKF 525A and troleandomycin potently suppressed the metabolism of
      both DP enantiomers with IC50 values for R(-)- and S(+)-DP of <7.3 and <18.9
      microM, respectively. In contrast, only weak inhibitory effects (i.e., IC50 > 100
      microM) were observed for five other representative CYP isoform substrates [i.e.,
      phenacetin (CYP1A1/2), sparteine (CYP2D6), tolbutamide (CYP2C9), S-mephenytoin
      (CYP2C19), and p-nitrophenol (CYP2E1)]. Significant correlations (P <.01, r =
      0.91) were found between the activities of 11 different human liver microsomes
      for mono-N-dealkylation of both DP enantiomers and that of 6beta-hydroxylation of
      testosterone. Conversely, no significant correlations were observed between the
      catalytic activities for DP enantiomers and those for the O-deethylation of
      phenacetin, 2-hydroxylation of desipramine, hydroxylation of tolbutamide, and 4'
      hydroxylation of S-mephenytoin. Further evidence for involvement of CYP3A P450s
      was revealed by an anti-human CYP3A serum that inhibited the mono-N-dealkylation
      of both DP enantiomers and 6beta-hydroxylation of testosterone almost completely
      (i.e., >90%), whereas it only weakly inhibited (i.e., <15%) CYP1A1/2- or 2C19
      mediated reactions. Finally, the recombinant human CYP3A3 and 3A4 showed much
      greater catalytic activities than seven other isoforms examined (i.e., CYP1A2,
      2A6, 2B6, 2C9, 2D6, 2E1, and 3A5) for both DP enantiomers. In conclusion, the
      metabolism of both DP enantiomers in humans would primarily be catalyzed by
      CYP3A4, implying that DP may have an interaction potential with other CYP3A
      substrates and/or inhibitors.

PMID- 10901705
TI  - Phenytoin metabolism by human cytochrome P450: involvement of P450 3A and 2C
      forms in secondary metabolism and drug-protein adduct formation.
AB  - The anticonvulsant phenytoin (5,5-diphenylhydantoin) provokes a skin rash in 5 to
      10% of patients, which heralds the start of an idiosyncratic reaction that may
      result from covalent modification of normal self proteins by reactive drug
      metabolites. Phenytoin is metabolized by cytochrome P450 (P450) enzymes primarily
      to 5-(p-hydroxyphenyl-),5-phenylhydantoin (HPPH), which may be further
      metabolized to a catechol that spontaneously oxidizes to semiquinone and quinone
      species that covalently modify proteins. The aim of this study was to determine
      which P450s catalyze HPPH metabolism to the catechol, proposed to be the final
      enzymatic step in phenytoin bioactivation. Recombinant human P450s were
      coexpressed with NADPH-cytochrome P450 reductase in Escherichia coli. Novel
      bicistronic expression vectors were constructed for P450 2C19 and the three major
      variants of P450 2C9, i.e., 2C9*1, 2C9*2, and 2C9*3. HPPH metabolism and covalent
      adduct formation were assessed in parallel. P450 2C19 was the most effective
      catalyst of HPPH oxidation to the catechol metabolite and was also associated
      with the highest levels of covalent adduct formation. P450 3A4, 3A5, 3A7, 2C9*1,
      and 2C9*2 also catalyzed bioactivation of HPPH, but to a lesser extent.
      Fluorographic analysis showed that the major targets of adduct formation in
      bacterial membranes were the catalytic P450 forms, as suggested from experiments
      with human liver microsomes. These results suggest that P450 2C19 and other forms
      from the 2C and 3A subfamilies may be targets as well as catalysts of drug
      protein adduct formation from phenytoin.

PMID- 10901706
TI  - Glutathione S-transferase metabolism of the antineoplastic
      pentafluorophenylsulfonamide in tissue culture and mice.
AB  - The microtubule disrupting agent 2-fluoro-1-methoxy-4-pentafluorophenylsu
      lfonamidobenzene (T138067) binds covalently and selectively to beta-tubulin and
      has been shown to evade drug-efflux pumps that confer multidrug resistance to
      other antimitotic drugs that are used in cancer chemotherapy (Shan et al., 1999).
      In addition to these resistance mechanisms, eukaryotic cells have developed other
      protection mechanisms that involve enzymes that modify electrophilic xenobiotics.
      To determine whether T138067 is a substrate for such enzymatic detoxification
      pathways, a metabolism study was initiated. GSH conjugation was shown to play a
      major role in T138067 metabolism. T138067-GSH conjugates were isolated from the
      culture media of T138067-treated cells and the bile of mice treated i.v. with
      T138067. The major T138067-GSH degradation products were also isolated from these
      sources. 19F NMR studies of the metabolites showed that metabolic conversions
      occurred through substitution of the para fluorine atom in the pentafluorophenyl
      ring of T138067. The T138067-GSH conjugate was also isolated from T138067
      incubation buffer that had been exposed to mouse, rat, dog, or human liver
      slices, suggesting that this mechanism is not species-specific. All three human
      glutathione S-transferases (alpha, mu, and pi), which are expressed in a wide
      variety of tissues including human tumors, were shown to metabolize T138067
      effectively in vitro. The combined data show that T138067 is being metabolized,
      in vitro and in vivo, predominantly via a glutathione S-transferase-mediated
      metabolic pathway.

PMID- 10901707
TI  - Involvement of CYP1A2 and CYP3A4 in lidocaine N-deethylation and 3-hydroxylation
      in humans.
AB  - The roles of cytochrome P-450 (CYP) enzymes in the N-deethylation, i.e.,
      formation of monoethylglycinexylidide (MEGX), and 3-hydroxylation of lidocaine
      were studied with human liver microsomes and recombinant human CYP isoforms. Both
      CYP1A2 and CYP3A4 were found to be capable of catalyzing the formation of MEGX
      and 3-OH-lidocaine. Lidocaine N-deethylation by liver microsomes was strongly
      inhibited by furafylline (by about 60%) and anti-CYP1A1/2 antibodies (>75%) at 5
      microM lidocaine, suggesting that CYP1A2 was the major isoform catalyzing
      lidocaine N-deethylation at low (therapeutically relevant) lidocaine
      concentrations. Troleandomycin inhibited the N-deethylation of lidocaine by about
      50% at 800 microM lidocaine, suggesting that the role of CYP3A4 may be more
      important than that of CYP1A2 at high lidocaine concentrations. Chemical
      inhibition and immunoinhibition studies also indicated that 3-OH-lidocaine
      formation was catalyzed almost exclusively by CYP1A2, CYP3A4 playing only a minor
      role. Although the CYP2C9 inhibitor sulfaphenazole (100 microM) inhibited MEGX
      formation by about 30%, recombinant human CYP2C9 showed very low catalytic
      activity, suggesting a negligible role for this enzyme in lidocaine N
      deethylation. Chemical inhibition studies indicated that CYP2C19, CYP2D6, and
      CYP2E1 did not play significant roles in the metabolism of lidocaine in vitro.
      Taken together, these results demonstrate that CYP1A2 and CYP3A4 enzymes are the
      major CYP isoforms involved in lidocaine N-deethylation. Therefore, the MEGX test
      (formation of MEGX from lidocaine) is not a suitable marker of hepatic CYP3A4
      activity in vivo.

PMID- 10901708
TI  - Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes.
AB  - This study demonstrates the stereoselective metabolism of the optical isomers of
      omeprazole in human liver microsomes. The intrinsic clearance (CL(int)) of the
      formation of the hydroxy metabolite from S-omeprazole was 10-fold lower than that
      from R-omeprazole. However, the CL(int) value for the sulfone and 5-O-desmethyl
      metabolites from S-omeprazole was higher than that from R-omeprazole. The sum of
      the CL(int) of the formation of all three metabolites was 14.6 and 42.5
      microl/min/mg protein for S- and R-omeprazole, respectively. This indicates that
      S-omeprazole is cleared more slowly than R-omeprazole in vivo. The
      stereoselective metabolism of the optical isomers is mediated primarily by
      cytochrome P450 (CYP) 2C19, as indicated by studies using cDNA-expressed enzymes.
      This is the result of a considerably higher CL(int) of the 5-hydroxy metabolite
      formation for R- than for S-omeprazole. For S-omeprazole, CYP2C19 is more
      important for 5-O-desmethyl formation than for 5-hydroxylation. Predictions of
      the CL(int) using data from cDNA-expressed enzymes suggest that CYP2C19 is
      responsible for 40 and 87% of the total CL(int) of S- and R-omeprazole,
      respectively, in human liver microsomes. According to experiments using cDNA
      expressed enzymes, the sulfoxidation of both optical isomers is metabolized by a
      single isoform, CYP3A4. The CL(int) of the sulfone formation by CYP3A4 is 10-fold
      higher for S-omeprazole than for R-omeprazole, which may contribute to their
      stereoselective disposition. The results of this study show that both CYP2C19 and
      CYP3A4 exhibit a stereoselective metabolism of omeprazole. CYP2C19 favors 5
      hydroxylation of the pyridine group of R-omeprazole, whereas the same enzyme
      mainly 5-O-demethylates S-omeprazole in the benzimidazole group. Sulfoxidation
      mediated by CYP3A4 highly favors the S-form.

PMID- 10901709
TI  - Disposition of radiolabeled ifetroban in rats, dogs, monkeys, and humans.
AB  - Ifetroban is a potent and selective thromboxane receptor antagonist. This study
      was conducted to characterize the pharmacokinetics, absolute bioavailability, and
      disposition of ifetroban after i.v. and oral administrations of [14C]ifetroban or
      [3H]ifetroban in rats (3 mg/kg), dogs (1 mg/kg), monkeys (1 mg/kg), and humans
      (50 mg). The drug was rapidly absorbed after oral administration, with peak
      plasma concentrations occurring between 5 and 20 min across species. Plasma
      terminal elimination half-life was approximately 8 h in rats, approximately 20 h
      in dogs, approximately 27 h in monkeys, and approximately 22 h in humans. Based
      on the steady-state volume of distribution, the drug was extensively distributed
      in tissues. Absolute bioavailability was 25, 35, 23, and 48% in rats, dogs,
      monkeys, and humans, respectively. Renal excretion was a minor route of
      elimination in all species, with the majority of the dose being excreted into the
      feces. After a single oral dose, urinary excretion accounted for 3% of the
      administered dose in rats and dogs, 14% in monkeys, and 27% in humans, with the
      remainder excreted in the feces. Extensive biliary excretion was observed in rats
      with the hydroxylated metabolite at the C-14 position being the major metabolite
      observed in rat bile. Ifetroban was extensively metabolized after oral
      administration. Approximately 40 to 50% of the radioactivity in rat and dog
      plasma was accounted for by parent drug whereas, in humans, approximately 60% of
      the plasma radioactivity was accounted for by ifetroban acylglucuronide.

PMID- 10901710
TI  - Cloning of canine cytochrome P450 2E1 cDNA: identification and characterization
      of two variant alleles.
AB  - Cytochrome P450 (CYP) 2E1 is a toxicologically important enzyme that inactivates
      a number of drugs and xenobiotics and also bioactivates many xenobiotic
      substrates to their hepatotoxic or carcinogenic forms. Although cDNAs for the
      human, rodent, and rabbit forms of CYP2E1 have been isolated and studied
      extensively, there is an absence of information about canine CYP2E1, despite the
      fact that the dog is routinely used in drug safety studies. In this study, we
      isolated and sequenced a full-length CYP2E1 cDNA from a beagle liver cDNA
      library. The deduced canine CYP2E1 amino acid sequence exhibited 75 to 76%
      identity with rat, mouse, and rabbit CYP2E1 sequences, and 77% identity with
      human CYP2E1. Two populations of clones, differing at a single nucleotide, were
      isolated from the unamplified library. The T1453C base change results in a
      Tyr485His amino acid substitution, which is well beyond the heme binding region
      but is possibly part of a beta-sheet structure. An allele-specific polymerase
      chain reaction-based restriction enzyme test was developed for genotyping
      individual dogs from genomic DNA samples. One hundred mixed breed dogs were
      genotyped, and the frequencies of the Tyr485 and His485 alleles were found to be
      0. 85 and 0.15, respectively. The canine Tyr485 and His485 alleles and human
      CYP2E1 were expressed in Escherichia coli cells, and catalytic activities of the
      proteins were assessed using the substrate chlorzoxazone. Although the two canine
      enzymes had similar catalytic activity; significant kinetic differences were seen
      between canine and human CYP2E1s.

PMID- 10901711
TI  - Detection of cytochrome P450 and other drug-metabolizing enzyme mRNAs in
      peripheral blood mononuclear cells using DNA arrays.
AB  - The purpose of this study was to determine whether the expression of cytochrome
      P450 (CYP) enzyme mRNAs, other drug-metabolizing enzyme mRNAs, and transporter
      mRNAs can be detected using DNA arrays. Total RNA was isolated from peripheral
      blood mononuclear cells of 10 multiple sclerosis patients and 10 age- and sex
      matched controls. The mRNA was reverse transcribed to radiolabeled cDNA, and the
      resultant cDNA was used to probe a DNA array containing several thousand known
      human genes. The signals corresponding to several CYPs, drug-metabolizing, and
      transporter mRNAs was substantially above background. The results demonstrate
      that the DNA array technique has the sensitivity and the selectivity for
      applications in the pharmaceutical sciences. The mean values for mRNAs of
      specific CYPs and drug-metabolizing enzymes in peripheral blood cells were
      compared with reported values for liver. The capabilities of DNA arrays may prove
      useful for characterizing CYP expression in a variety of clinical samples.

PMID- 10901712
TI  - Three- and four-dimensional-quantitative structure activity relationship (3D/4D
      QSAR) analyses of CYP2C9 inhibitors.
AB  - The interaction of competitive type inhibitors with the active site of cytochrome
      P450 (CYP) 2C9 has been predicted using three- and four-dimensional quantitative
      structure activity relationship (3D-/4D-QSAR) models constructed using previously
      unreported and literature-derived data. 3D-QSAR pharmacophore models of the
      common structural features of CYP2C9 inhibitors were built using the program
      Catalyst and compared with 3D- and 4D-QSAR partial least-squares models, which
      use molecular surface-weighted holistic invariant molecular descriptors of the
      size and shape of inhibitors. The Catalyst models generated from multiple
      conformers of competitive inhibitors of CYP2C9 activities contained at least one
      hydrophobic and two hydrogen bond acceptor/donor regions. Catalyst model 1 was
      constructed with Ki(apparent) values for inhibitors of tolbutamide and diclofenac
      4'-hydroxylation (n = 9). Catalyst model 2 was generated from literature
      Ki(apparent) values for (S)-warfarin 7-hydroxylation (n = 29), and Catalyst model
      3 from literature IC50 values for tolbutamide 4-hydroxylation (n = 13). These
      three models illustrated correlation values of observed and predicted inhibition
      for CYP2C9 of r = 0.91, 0.89, and 0.71, respectively. Catalyst pharmacophores
      generated with Ki(apparent) values were validated by predicting the Ki(apparent)
      value of a test set of CYP2C9 inhibitors also derived from the literature (n =
      14). Twelve of fourteen of these Ki(apparent) values were predicted to be within
      1 log residual of the observed value using Catalyst model 1, whereas Catalyst
      model 2 predicted 10 of 14 Ki(apparent) values. The corresponding partial least
      squares molecular surface-weighted holistic invariant molecular 3D- and 4D-QSAR
      models for all CYP2C9 data sets yielded predictable models as assessed using
      cross-validation. These 3D- and 4D-QSAR models of CYP inhibition will aid in
      future prediction of drug-drug interactions.

PMID- 10901713
TI  - Size limits of thiocarbamides accepted as substrates by human flavin-containing
      monooxygenase 1.
AB  - Microsomes isolated from Spodoptera frugiperda (Sf)9 cells infected with human
      flavin-containing monooxygenase (FMO)1 recombinant baculovirus catalyzed the
      NADPH- and O2-dependent oxidation of methimazole, thiourea, and phenylthiourea.
      However, there was no detectable activity with 1,3-diphenylthiourea or larger
      thiocarbamides. Microsomes from control Sf9 cells were devoid of methimazole or
      thiourea S-oxygenase activity. Trimethylamine up to 1.0 mM had no detectable
      effect on the oxidation of 10 microM methimazole (Km = 5 microM) but 1.0 mM N,N
      dimethylaniline or chlorpromazine inhibited the oxidation of 1.0 mM methimazole
      50 and 70%, respectively. Although products were not isolated, the pronounced
      inhibition of methimazole S-oxygenation suggests that these amines are alternate
      substrates for human FMO1. Because 1,3-diphenylthiourea is apparently completely
      excluded from the catalytic site, tricyclic amine drugs are probably approaching
      the upper size limits of xenobiotics accepted by human FMO1. The substrate
      specificity of this isoform in humans appears considerably more restricted than
      that of pig or guinea pig FMO1. Differences in the size of nucleophiles accepted
      must be considered in attempting to extrapolate the extensive structure-activity
      studies available for pig FMO1 to this FMO isoform in humans.

PMID- 10901714
TI  - A case of dermatitis herpetiformis with IgA endomysial antibodies but negative
      direct immunofluorescent findings.
AB  - A patient with clinical findings of dermatitis herpetiformis (DH), negative
      direct immunofluorescent (DIF) findings for junctional IgA deposits in 2 biopsy
      specimens, and positive for IgA endomysial (AEmA) and tissue transglutaminase
      (tTG) antibodies responded initially to dapsone. After dapsone had to be
      discontinued because of side effects, a gluten-free diet and supportive therapy
      controlled the disease; the AEmA and tTG antibodies became negative. Our data on
      10 consecutive DH cases examined by DIF and by serum studies for AEmA and
      antibodies to tTG, point to frequencies of 90% DIF positive and 70% AEmA and tTG
      positive cases. The use of both DIF and serum tests for AEmA and tTG reveals DH
      cases not detected by DIF alone that respond to gluten-free diet. Findings on
      autoantibodies to tTG, an enzyme that metabolizes gliadin, points to a role of
      tTG in the immunopathology of gluten-sensitive enteropathy and helps to explain
      the need for a gluten-free diet in the management of DH cases.

PMID- 10901715
TI  - Cutaneous Mycobacterium chelonae in a liver transplant patient.
AB  - A 51-year-old woman with an orthotopic liver transplant on tacrolimus (SKF 506)
      and prednisone presented with an erythematous ulcerated nodule on the knee. No
      preceding trauma was noted. A skin biopsy specimen demonstrated beaded gram
      positive, acid-fast rods and the skin culture grew Mycobacterium chelonae
      (formerly M chelonae subsp chelonae ). This report describes the first case in a
      liver transplant patient of cutaneous Mycobacterium chelonae under the current
      method of designating atypical Mycobacterium species.

PMID- 10901716
TI  - Osteoma cutis coexisting with cutis laxa-like pseudoxanthoma elasticum.
AB  - Pseudoxanthoma elasticum (PXE) is a heritable disorder of elastic fibers
      characterized by yellowish, coalescing papules on the loose and wrinkled flexural
      area. There have been no reports of osteoma cutis associated with PXE. A 17-year
      old Korean girl presented cutis laxa-like marked wrinkling on the flexural area,
      and a skin biopsy specimen revealed multiple foci of ossification with
      irregularly clumped, basophilic-stained elastic fibers in the reticular dermis
      and calcium deposits along the elastic fibers. Ultrasonographic evaluation showed
      multiple tiny osteomas diffusely scattered along the entire abdominal wall,
      axillae, and medial aspect of the upper arms. We report the first case of osteoma
      cutis coexisting with cutis laxa-like PXE.

PMID- 10901717
TI  - Large plantar wart caused by human papillomavirus-66 and resolution by topical
      cidofovir therapy.
AB  - Warts can be difficult to diagnose and to treat in the setting of human
      immunodeficiency virus (HIV) infection. A 37-year-old woman with a background of
      HIV presented with a large verrucous plaque involving her right foot. Human
      papillomavirus (HPV)-66 was identified in the lesional skin biopsy sample and in
      scrapings obtained from her cervix. The wart rapidly responded to topical
      cidofovir therapy. HPV-66 is a novel HPV type to be associated with verruca
      vulgaris. Topical cidofovir should be further investigated as an alternative
      treatment modality for verruca vulgaris.

PMID- 10901718
TI  - Primary cutaneous cryptococcosis of the nose in an immunocompetent woman.
AB  - Cutaneous manifestations of Cryptococcus neoformans in immunocompromised persons
      have been well documented. We report a case of localized skin involvement after
      an abrasion in a healthy host. It presented as chronic ulcerative nodules that
      resolved after fluconazole therapy.

PMID- 10901719
TI  - Generalized lichen amyloidosis associated with chronic lichen planus.
AB  - The development of lichen amyloidosis in a patient with chronic lichen planus is
      reported. To our knowledge, this is the first report of the coexistence of these
      2 diseases. The disparate response of the 2 conditions to etretinate is
      discussed.

PMID- 10901720
TI  - Idiopathic familial onychomadesis.
AB  - Onychomadesis is defined as spontaneous separation of the nail plate from the
      nail bed, beginning at its proximal end and resulting in the shedding of the
      nail. It has been associated with a variety of clinical settings, including
      systemic illnesses, generalized skin diseases, and drug therapies. There have
      been a small number of reports in the older literature of idiopathic
      onychomadesis occurring in a familial pattern. We report the case of a healthy 12
      year-old girl and her mother, both of whom have experienced recurrent
      onychomadesis affecting multiple digits, and in the absence of any causal disease
      or medication.

PMID- 10901721
TI  - Cutaneous malakoplakia: a report of two cases with the use of anti-BCG for the
      detection for micro-organisms.
AB  - Malakoplakia is an uncommon granulomatous infectious disease that is found
      primarily in the genito-urinary tract, but may rarely involve the skin.
      Histologic findings are marked by the presence of foamy macrophages containing
      basophilic concentric spherules, the Michaelis-Gutman bodies. Micro-organisms are
      not readily identifiable. Immunostaining with polyclonal anti-mycobacterium bovis
      (BCG) has been described as a method of identifying bacterial and fungal
      organisms in situations where organisms may be sparse. We report 2 cases of
      cutaneous malakoplakia with demonstration of organisms by immunostaining with
      anti-BCG antibodies.

PMID- 10901722
TI  - Erythematous plaques due to platelet plugging: a clue to underlying
      myeloproliferative disorder.
AB  - We report a syndrome in a middle-aged woman characterized by tender erythematous
      plaques with histologic evidence of dramatic dermal vessel occlusion. These
      cutaneous findings occurred in association with progressive inferior vena cava
      and portal vein thrombosis while on coumarin anticoagulation, following hepatic
      transplantation for Budd-Chiari syndrome. The material occluding dermal vessels
      was proven by immunohistochemical staining to be platelet plugs. These findings
      led to the diagnosis of an underlying myeloproliferative disorder explaining both
      her cutaneous and liver abnormalities and institution of appropriate platelet
      directed anticoagulation with aspirin.

PMID- 10901723
TI  - A case of cutaneous reaction to chemotherapeutic agents showing epidermal
      dysmaturation.
AB  - Cutaneous chemotherapy reactions are more likely to be toxic than allergic.
      Epidermal dysmaturation refers to histologic changes that may be observed in the
      epidermis after any significant cytoreductive therapy. We report a case of
      epidermal dysmaturation occurring in a patient with acute myelogenous leukemia
      after antineoplastic chemotherapy.

PMID- 10901724
TI  - Unilateral lentiginosis with nevus depigmentosus on the other side.
AB  - A transmittance of unilateral hypomelanosis in 4 generations and the co
      occurrence of unilateral lentigenosis in the youngest family member are reported.
      It can be explained by paradominant inheritance and the twin-spot theory.

PMID- 10901725
TI  - Porokeratotic eccrine ostial and dermal duct nevus: a case report and review of
      the literature.
AB  - Hamartomas with eccrine differentiation are quite rare. There are 5 accepted
      classifications: eccrine nevus, eccrine-centered nevus, eccrine angiomatous
      hamartoma, eccrine syringofibroadenoma, and porokeratotic eccrine ostial and
      dermal duct nevus. The latter, PEODDN, typically presents as congenital keratotic
      papules and plaques located on the distal extremities. We report a classic case
      of PEODDN that was localized to the left hand since early childhood. The
      literature on this rare benign tumor is also reviewed.

PMID- 10901726
TI  - Squamous cell carcinoma arising in Hailey-Hailey disease.
AB  - Hailey-Hailey disease is a recurrent, autosomal dominant vesiculobullous
      dermatotis with a predilection for intertrigenous areas. We report what we
      believe to be the first case of squamous cell carcinoma arising de novo in a skin
      lesion of Hailey-Hailey disease. The occurrence of malignant neoplasms arising in
      the skin lesions of Hailey-Hailey disease and other acantholytic dermatoses is
      reviewed.

PMID- 10901727
TI  - Sarcoidal tissue reaction in Sezary syndrome.
AB  - Sezary syndrome (SS) is an erythrodermic and leukemic variant of cutaneous T-cell
      lymphoma (CTCL). Occasionally, the histology of CTCL exhibits evidence of a
      granulomatous infiltrate in the skin. A case of SS that showed epithelioid
      granulomas resembling sarcoidosis in the skin and lymph nodes is presented. The
      clinical course of this patient has been relatively indolent.

PMID- 10901728
TI  - Solitary cutaneous myxoma.
AB  - We describe a case of a large pedunculated solitary cutaneous myxoma arising on
      the thigh of a 47-year-old man without evidence of Carney's complex, NAME, or
      LAMB syndromes. The diagnosis was confirmed by hematoxylin and eosin stain,
      special stains, and immunocytochemistry studies. The tumor was surgically
      resected with no evidence of recurrence after 6 months. Solitary cutaneous myxoma
      should be differentiated histologically from myxoid neurofibroma, neurothekeoma,
      and ossifying and nonossifying fibromyxoid tumor.

PMID- 10901729
TI  - Epidermal naevus with Darier's disease-like changes in a patient with Gardner's
      syndrome.
AB  - We describe the unique presentation of a linear epidermal nevus with histologic
      features of Darier's disease occurring in a patient with Gardner's syndrome.
      Classification of localized forms of Darier's disease as an epidermal nevus or as
      a genetic mosaicism remains controversial. The association of this disorder with
      Gardner's syndrome has not been described in the literature before.

PMID- 10901730
TI  - Mercury-induced nummular dermatitis.
AB  - We report 2 cases of relapsing nummular dermatitis according to mercury
      sensitivity, which was confirmed by patch testing. Removal of the amalgam from
      dental metal alloys markedly improved their skin eruptions. One of the patients,
      a dentist, experienced exacerbation of the eruptions on his lower legs after
      handling dental amalgam. Hypersensitivity to haptens such as metals is possibly
      involved in, at least in some patients, the pathogenesis of nummular dermatitis.

PMID- 10901731
TI  - The sign of Leser-Trelat in a case of adenocarcinoma of the lung.
AB  - This is what we believe to be the first report of the sign of Leser-Trelat in
      association with occult adenocarcinoma of the lung. The sign of Leser-Trelat is
      proposed as a sign of possible occult malignancy, despite various suggestions to
      the contrary. Also, it is suggested that a tumor-produced humoral factor (eg,
      transforming growth factor-alpha [TGF-alpha]) could be responsible for both the
      acute eruption of the monomorphous seborrheic keratoses and the nearly
      concomitant development of acanthosis nigricans, which occurred in our case. The
      possible distinction between a hyperplastic and a neoplastic origin of various
      types of seborrheic keratosis is discussed in relation to this hypothetical
      humoral factor. In addition, we suggest a refinement of the definition of the
      sign of Leser-Trelat and discuss the use of "sign of Leser-Trelat" and "syndrome
      of Leser-Trelat" in relation to physical findings. All patients with the sign of
      Leser-Trelat should undergo a thorough evaluation for occult malignancy.

PMID- 10901732
TI  - Rapid improvement of psoriasis vulgaris during drug-induced agranulocytosis.
AB  - The role of neutrophils in psoriasis has long been discussed. We report a patient
      with long-standing psoriasis vulgaris who showed rapid improvement during
      agranulocytosis caused by ticlopidine. The patient did not develop any new
      psoriatic lesions for several days, although neutrophils increased daily after
      the administration of ticlopidine was stopped. The day after the peripheral blood
      neutrophil count recovered, several psoriatic plaques reappeared. The correlation
      of psoriatic activity with peripheral blood neutrophil counts suggests that a
      certain number of neutrophils may be required to initiate and maintain psoriasis.

PMID- 10901733
TI  - Acral steatocystoma multiplex.
AB  - Steatocystoma multiplex (SM) is characterized by multiple, widespread cutaneous
      cystic lesions. These lesions can appear virtually anywhere on the body but are
      more common in areas where the pilosebaceous apparatus is well developed, such as
      the trunk (especially the presternal area), neck, axilla, inguinal region, scalp,
      and proximal extremities. We present a case of a woman with predominantly acrally
      located SM. To the best of our knowledge, a predominantly acral distribution has
      never been reported. We hypothesize that this patient's phenotype may be due to
      her genetic predisposition, possibly involving a familial defect in keratin 17,
      in combination with "ectopic" acral sebaceous follicles.

PMID- 10901734
TI  - Treatment of keratoderma blennorrhagicum with tazarotene gel 0.1%.
AB  - We report near clearing of keratoderma blennorrhagicum following topical
      application of tazarotene gel 0.1%. This is the first report detailing the use of
      tazarotene gel for this purpose.

PMID- 10901735
TI  - Scleromyxedema: response to high-dose intravenous immunoglobulin (hdIVIg).
AB  - We report 2 patients with scleromyxedema, both associated with IgG-lambda
      paraproteinemia, who were treated with high-dose intravenous immunoglobulin
      (hdIVIg) 2g/kg per month. The response to treatment was assessed using an
      objective skin scoring system initially established for patients with
      scleroderma. This system grades the overall severity of the induration and the
      reduction in mobility of the skin. Both patients initially had a dramatic
      response to treatment which was sustained in one patient. The first patient, a 30
      year-old black man, showed a reduction in skin scores from 36/60 to 11/60 over a
      3-month period, during which time he had 3 infusions of hdIVIg. After an
      unplanned 2-month break from treatment, severe neuromuscular complications
      developed. These improved initially with more frequent infusions of hdIVIg but
      oral corticosteroids were required to treat worsening myopathy. Unfortunately,
      the initial response to hdIVIg has not been sustained and his skin scores at 1
      year returned to baseline. The second patient, a 60-year-old white man, showed a
      similarly dramatic reduction in skin scores from 36/60 to 15/60 over a 3-month
      period after having received only 2 infusions of hdIVIg. There has been sustained
      improvement after 10 months of therapy and the interval between hdIVIg infusions
      has been increased to 10 weeks without deterioration. HdIVIg may be an effective
      treatment for some patients with scleromyxedema, a rare condition with few
      effective treatments and a poor prognosis.

PMID- 10901736
TI  - Patients need nudge from doctors to get colorectal cancer screening.

PMID- 10901737
TI  - Cancer prevention: from concept to practice.

PMID- 10901738
TI  - New treatments for smoking cessation.
AB  - Helping cigarette smokers to permanently stop smoking is one of the most
      effective ways to prevent cancer. A physician's instruction to a patient to stop
      smoking and to offer assistance in this endeavor is an important motivator.
      Current guidelines state that clinicians should encourage all smokers who want to
      quit to use medications and should offer psychosocial therapies, as well. It has
      been shown that even brief clinician advice about smoking cessation increases
      quit rates. Five medications--bupropion, nicotine gum, nicotine inhaler, nicotine
      nasal spray, and nicotine patch--and one proven psychosocial therapy (behavior
      therapy) appear equally effective and safe; i.e., they all double quit rates and
      are associated with a less than 5% dropout rate due to adverse events. In 1998,
      approximately one third of those who attempted to quit smoking used a medication.
      Attending group behavior therapy to supplement medications increases quit rates
      but is not essential for medications to work. As there are no proven treatment
      matching protocols, patients should choose the treatment(s) they believe will be
      most effective for them. In the future, people who continue to smoke will be
      individuals with severe nicotine dependence or psychiatric symptoms; thus,
      clinicians will increasingly be called on to provide pharmacotherapy for smoking
      cessation.

PMID- 10901739
TI  - Breast cancer prevention: a review of current evidence.
AB  - The National Cancer Institute has created a breast cancer risk assessment tool
      that quickly estimates a woman's individualized absolute risk of developing
      breast cancer. Understanding the magnitude of risk is important because recent
      data show that breast cancer incidence may be reduced. All women may improve
      their overall health and thus perhaps minimize breast cancer risk by maintaining
      a healthy weight, avoiding cigarettes, limiting alcohol consumption, getting
      regular exercise, and avoiding non-diagnostic ionizing radiation. Nevertheless,
      no lifestyle modifications have yet been proven to prevent or definitively lower
      the risk of breast cancer. In addition, women whose personal breast cancer risk
      is high may consider reducing risk by pharmacologic or surgical means. In such
      women, a five-year course of tamoxifen reduced the risk of invasive breast cancer
      by 49%; women with lobular carcinoma in situ or atypical hyperplasia experienced
      even greater risk reductions. Because of the potential for vascular and
      endometrial side effects, women who are candidates for a preventive course of
      tamoxifen must be counseled regarding its relative risks and benefits.
      Prophylactic mastectomy offers at least a 90% reduction in the risk of breast
      cancer, but the physical and psychological changes involved in such a procedure
      make it a difficult choice for many women. Breast cancer risk assessment and
      appropriate counseling are becoming standard components of breast cancer
      screening and overall health maintenance.

PMID- 10901740
TI  - Clinical highlights from the National Cancer Data Base, 2000.
AB  - The National Cancer Data Base (NCDB) is the empirical data collection and
      analysis arm of the American College of Surgeons Commission on Cancer, and is
      supported in part by the American Cancer Society. The NCDB collects oncology
      patient demographic information, diagnostic and treatment information, and
      outcomes data from a broad spectrum of hospital-based cancer registries
      throughout the US, ranging from large research and teaching facilities to small
      community hospitals. Through this unique network, data are aggregated and
      reported back to participating hospitals to allow individual facilities to
      evaluate local patient care practices and outcomes. This article highlights the
      principal findings of articles published in 1999 and early 2000 that used NCDB
      data as the empirical basis of their analyses. Included among these are articles
      on breast cancer, gastric carcinoma, head and neck cancers, leukemia, liver
      carcinoma, lung cancer, parathyroid tumors, prostate carcinoma, small bowel
      adenocarcinoma, testicular malignancies, and vulvar melanoma. These articles are
      based on cases diagnosed between 1985 and 1996. The NCDB has accrued more than
      6.4 million cancer cases for this time period. Sufficient numbers of rare cancers
      are reported to the NCDB to permit some types of clinical evaluation not possible
      using other data sources.

PMID- 10901741
TI  - The diagnosis and management of ductal carcinoma in-situ of the breast.
AB  - The widespread utilization of screening mammography has produced a shift in the
      stage of breast cancer at diagnosis in the US: Currently, 12% to 15% of newly
      diagnosed breast cancer cases annually are ductal carcinoma in-situ (DCIS). The
      diagnosis is made, in at least 90% of patients, with mammography. Only about 10%
      of patients will have a palpable mass. The accurate characterization and
      visualization of calcifications typically requires magnification of mammographic
      imaging. The morphology of the calcifications is generally considered to be the
      most important factor in differentiating benign from malignant formations. Round
      and uniform shapes are more likely to be benign, while linear and heterogeneous
      morphologies are associated with DCIS. Following a complete mammographic work-up,
      most suspicious lesions are potential candidates for a stereotactic core needle
      biopsy. Ten percent to 50% of patients initially diagnosed with atypical ductal
      hyperplasia by needle biopsy have subsequently been surgically diagnosed with
      cancer near the biopsy site. Due to this relatively high incidence of co-existent
      carcinoma, a needle biopsy diagnosis of atypical ductal hyperplasia necessitates
      subsequent surgical excision. The most important change in our thinking about
      DCIS was from a monolithic view, conceiving of DCIS as a single disease highly
      likely to invade if left untreated, to the realization that DCIS represents a non
      obligate precursor with a variable risk of progression, depending on a
      combination of factors, such as histology, lesion, size, and margin status. In
      discussing treatment options, patients should understand that local recurrence
      following total mastectomy is rare and that this is the procedure of choice for
      disease that cannot be adequately encompassed with a breast-conserving approach.
      If the patient and her surgeon are in agreement about proceeding with a breast
      conserving approach, there needs to be a clear understanding of the incidence and
      implications of local recurrence. In all such discussions with newly diagnosed
      patients, however, it is essential to emphasize the excellent prognosis with this
      disease, irrespective of the surgical approach.

PMID- 10901742
TI  - Atherosclerosis in the young: risk and prevention.

PMID- 10901743
TI  - Autopsies and the risk of lawsuits.

PMID- 10901744
TI  - Warning about a medicinal herb.

PMID- 10901745
TI  - More tips on avoiding malpractice claims.

PMID- 10901746
TI  - Inverted T wave returning to upright during acute MI.

PMID- 10901747
TI  - AIDS, anemia, and an abnormal platelet count.

PMID- 10901748
TI  - Improving management of type 2 diabetes mellitus: 1. alpha-Glucosidase
      inhibitors.

PMID- 10901749
TI  - An unconscious and unresponsive young man.

PMID- 10901750
TI  - Dust mites and asthma.
AB  - Dust mite proteins have been implicated as a predominant cause of the current
      increase in asthma prevalence. Recent advances in the understanding of these
      allergens have vastly increased the potential for more effective treatment and
      prophylaxis. In the absence of vaccines, environmental controls aimed at allergen
      avoidance are currently the best defense against the disease.

PMID- 10901751
TI  - Nosocomial pneumococcal infection: an outbreak.
AB  - When an outbreak of pneumococcal disease occurs an institution--be it a hospital,
      nursing home, day care center, or other facility--management includes treatment
      of affected cases and prevention of new cases. Patients and staff should be
      tested for nasopharyngeal carriage and their vaccination status ascertained.
      Antibiotic use should be reviewed, especially if the causative strain is
      resistant.

PMID- 10901752
TI  - The prospects for antisense therapy.
AB  - The use of short spans of nucleic acid--DNA or RNA--to disrupt the expression of
      disease-related genetic code is an idea potentially applicable to a vast number
      of illnesses, including most neoplasms. On several fronts, including hematologic
      malignancies, the concept has reached clinical trials--where appreciation of the
      in vivo hurdles is leading to new approaches for delivery of this new magic
      bullet.

PMID- 10901753
TI  - Diagnosis and treatment of Klinefelter syndrome.
AB  - Many physicians underestimate the prevalence of Klinefelter syndrome and so fail
      to recognize its more obvious features. Increased awareness of its effects on
      physical, psychological, and social development should help to dispel persistent
      misconceptions about the condition and enable earlier diagnosis and more
      effective treatment.

PMID- 10901754
TI  - Case in point. Carcinoma of the ampulla of Vater.

PMID- 10901755
TI  - My new dishwasher and free-market health care.

PMID- 10901756
TI  - Triglycerides.

PMID- 10901757
TI  - Mitral regurgitation with conduction defects.

PMID- 10901758
TI  - Cardiac arrhythmia: current therapy.
AB  - Rhythm disturbances can range from the harmless to the life-threatening, and
      treatment varies accordingly, from watchful waiting to emergency intervention.
      Traditional antiarrhythmic medications have largely been supplanted by newer
      agents; pharmacologic therapy is giving way to device-based treatment, including
      pacemakers, defibrillators, and catheter ablation.

PMID- 10901759
TI  - Case in point. Abdominal pain secondary to hypertriglyceridemia.

PMID- 10901760
TI  - A four-part regimen for clinical heart failure.
AB  - Combination therapy with a diuretic, digoxin, ACE inhibitor, and beta-blocker can
      help patients with heart failure caused by severe systolic dysfunction feel
      better and live longer. Especially with ACE inhibitors and beta-blockers, the key
      to success is starting at low doses and titrating carefully to proven target
      doses. The demanding complexity of the four-drug regimen is well worth the
      results.

PMID- 10901762
TI  - Atherosclerosis: an infectious disease?
AB  - Traditional risk factors do not fully account for atherogenesis. There is
      increasing evidence that infectious pathogens, such as Helicobacter pylori,
      cytomegalovirus, and Chlamydia pneumoniae, may promote the atherosclerotic
      cascade. Proposed mechanisms include macrophage transformation, endothelial
      injury, chronic inflammation, and thrombosis. Specific antibiotic therapy may
      affect outcome.

PMID- 10901761
TI  - Giving triglycerides their due.
AB  - Often considered less important than other serum lipids, triglycerides are
      nevertheless an independent risk factor for coronary artery disease. Treatment
      may be indicated even when triglyceride levels are only mildly elevated and
      cholesterol readings are within the normal range. Detailed lipoprotein profiles,
      now clinically available, may guide decision making in such cases.

PMID- 10901763
TI  - Indicators and treatment of hypertensive heart disease.
AB  - The relation of systolic and diastolic pressure to hypertrophic cardiomyopathy
      and congestive heart failure must be understood if we are to recognize the
      earliest manifestations of hypertensive heart disease and prevent its
      progression. Many such issues have to be resolved before the most effective
      combination of medical and nonmedical therapies can be determined.

PMID- 10901764
TI  - Palpitations in a middle-aged woman.

PMID- 10901765
TI  - Eyeing pathogens in the peripheral blood film.

PMID- 10901766
TI  - Reconciliation, social equity and indigenous health.

PMID- 10901767
TI  - Schizophrenia today.

PMID- 10901768
TI  - Illness or disease? The case of chronic fatigue syndrome.

PMID- 10901769
TI  - Reducing premature death and renal failure in Australian aboriginals. A community
      based cardiovascular and renal protective program.
AB  - OBJECTIVE: To describe results of a systematic treatment program to modify renal
      and cardiovascular disease in an Aboriginal community whose rates of renal
      failure and cardiovascular deaths are among the highest in Australia. DESIGN:
      Longitudinal survey of people during treatment, and comparison of rates of
      natural death and renal failure with those in a historical control group.
      SETTING: Tiwi Islands (population, about 1800), November 1995 to December 1998.
      PARTICIPANTS: All adults with blood pressure > or = 140/90, with diabetes and
      urinary albumin/creatinine ratio (ACR) > or = 3.4 g/mol (microalbuminuria
      threshold), or with progressive overt albuminuria (ACR > or = 34 g/mol) were
      eligible for treatment. The historical control group comprised 229 people who
      satisfied these criteria in the pretreatment period 1992-1995. INTERVENTIONS:
      Perindopril, combined with calcium-channel blockers and diuretics if needed to
      achieve blood pressure goals; attempts to improve control of blood glucose and
      lipid levels; health education. MAIN OUTCOME MEASURES: Blood pressure, ACR, serum
      creatinine level and glomerular filtration rate (GFR) over two years of
      treatment; rates of renal failure and natural death compared with control group
      (analysed on intention-to-treat basis). RESULTS: 258 people enrolled in the
      program, and 118 had complete data for two years of treatment. In these 118,
      blood pressures fell significantly, while ACR and GFR stabilised. Rates of the
      combined endpoints of renal failure and natural death per 100 person-years were
      2.9 for the treatment group (95% CI, 1.7-4.6) and 4.8 for the control group (95%
      CI, 3.3-7.0). After adjustment for baseline ACR category, the relative risk of
      the treatment group versus the control group for these combined endpoints was
      0.47 (95% CI, 0.25-0.86; P = 0.013). Treatment benefit was especially marked in
      people with overt albuminuria or hypertension and in non-diabetic people. The
      estimates of benefit were supported by a fall in community rates of death and
      renal failure. CONCLUSIONS: Aboriginal people can participate enthusiastically in
      chronic disease management, with rapid, dramatic improvement in clinical profiles
      and mortality. Similar programs should be introduced urgently into other
      Aboriginal communities nationwide.

PMID- 10901770
TI  - Increase in prevalence of obesity and diabetes and decrease in plasma cholesterol
      in a central Australian aboriginal community.
AB  - OBJECTIVE: To document change in prevalence of obesity, diabetes and other
      cardiovascular disease (CVD) risk factors, and trends in dietary macronutrient
      intake, over an eight-year period in a rural Aboriginal community in central
      Australia. DESIGN: Sequential cross-sectional community surveys in 1987, 1991 and
      1995. SUBJECTS: All adults (15 years and over) in the community were invited to
      participate. In 1987, 1991 and 1995, 335 (87% of eligible adults), 331 (76%) and
      304 (68%), respectively, were surveyed. MAIN OUTCOME MEASURES: Body mass index
      and waist: hip ratio; blood glucose level and glucose tolerance; fasting total
      and high density lipoprotein (HDL) cholesterol and triglyceride levels; and
      apparent dietary intake (estimated by the store turnover method). INTERVENTION: A
      community-based nutrition awareness and healthy lifestyle program, 1988-1990.
      RESULTS: At the eight-year follow-up, the odds ratios (95% CIs) for CVD risk
      factors relative to baseline were obesity, 1.84 (1.28-2.66); diabetes, 1.83 (1.11
      3.03); hypercholesterolaemia, 0.29 (0.20-0.42); and dyslipidemia (high
      triglyceride plus low HDL cholesterol level), 4.54 (2.84-7.29). In younger women
      (15-24 years), there was a trembling in obesity prevalence and a four- to
      fivefold increase in diabetes prevalence. Store turnover data suggested a
      relative reduction in the consumption of refined carbohydrates and saturated
      fats. CONCLUSIONS: Interventions targeting nutritional factors alone are unlikely
      to greatly alter trends towards increasing prevalences of obesity and diabetes.
      In communities where healthy food choices are limited, the role of regular
      physical activity in improving metabolic fitness may also need to be emphasised.

PMID- 10901771
TI  - The incidence of inflatable rescue boat injuries in Queensland surf lifesavers.
AB  - OBJECTIVE: To estimate the current incidence of serious injuries in Queensland
      surf lifesavers related to inflatable rescue boat (IRB) use, and to describe the
      nature of the injuries. DESIGN: Descriptive study. PARTICIPANTS AND SETTING: The
      3050 members of Queensland's 57 surf life saving clubs who drove or crewed an IRB
      in Queensland between July 1997 and June 1998. MAIN OUTCOME MEASURES: Incidence
      of serious IRB-related injuries that resulted in claims for workers compensation
      in 1997-1998, and type and anatomical location of injury. RESULTS: Thirty-six IRB
      related injuries were lodged with WorkCover Queensland by surf lifesavers during
      1997-1998, giving an estimated crude incidence of 1.2%. Sixty-one per cent of
      injuries affected the right side of the body; two-thirds of these involved the
      knee, leg and ankle. IRB injuries occurred most often during patrol duty (39% of
      cases) and it was usually the crewperson (86% of cases) who was injured. Fracture
      and fracture-dislocations constituted a third of the injuries, with 75% occurring
      in the right leg and ankle. CONCLUSIONS: Despite the known incomplete reporting
      of these injuries, our findings suggest that IRB-related injury caused
      substantial morbidity among volunteer surf lifesavers. The pattern of injuries
      suggests biomechanically preventable causes.

PMID- 10901772
TI  - Socioeconomic determinants of health in Australia: policy responses and
      intervention options.
AB  - Tackling socioeconomic health inequalities represents one of Australia's most
      challenging public health issues. Research has demonstrated that the role of
      physicians and other health professionals, as advocates for change in the
      delivery of health services, public health policy and other community-wide
      initiatives, is extremely important in reducing mortality and improving health
      outcomes. Multilevel actions to reduce health inequalities should include changes
      to macrolevel social and economic policies; improving living and working
      conditions; strengthening communities for health; improving behavioural risk
      factors; empowering individuals and strengthening their social networks; and
      improving responses from the healthcare system and associated treatment services.
      Australia has yet to develop a coordinated and integrated approach to addressing
      health disparities; however, previously successful public health interventions
      addressing other health issues are good starting points.

PMID- 10901773
TI  - Clinical manifestations of gout and their management.
AB  - Gout is an inflammatory response to deposition of monosodium urate crystals in
      and around joints. It is primarily a disease of adult men. In acute gout,
      treatment options include non-steroidal anti-inflammatory drugs (NSAIDs),
      colchicine and corticosteroids, administered either intra-articularly, orally or
      parenterally. Asymptomatic hyperuricaemia does not require specific treatment,
      but should prompt screening for atherosclerosis risk factors, and general
      lifestyle modification to reduce serum urate levels. Gout presents differently in
      the elderly. Both women and men are affected, attacks are frequently
      polyarticular and in the upper limbs, and the gout may be associated with
      diuretic use, hypertension and renal impairment. In patients with peptic ulcer
      disease, selective COX-2 inhibitors provide another treatment option. In the
      presence of renal impairment, allopurinol is the treatment of choice for urate
      lowering therapy, but doses of allopurinol and colchicine must be adjusted. Urate
      lowering therapy should only be used if recurrent episodes of gout occur despite
      aggressive attempts to reverse or control the underlying causes. It should not be
      introduced or discontinued during an acute episode of gout, and gout prophylaxis
      (NSAIDs or colchicine) should be prescribed during the introduction of urate
      lowering therapy.

PMID- 10901775
TI  - Alopecia in the operating theatre: what are the bald facts?

PMID- 10901774
TI  - Fatal colchicine toxicity.

PMID- 10901776
TI  - Operation Safe Haven: the Leeuwin experience.

PMID- 10901777
TI  - Neurology. 3: Dizziness.
AB  - The differential diagnosis of dizziness includes vertigo as well as numerous
      other causes of faintness or lightheadedness. Vertigo is a common symptom that
      has diverse causes. Because of uncertainties about the diagnosis, many patients
      are treated symptomatically without a specific diagnosis being made. Most
      patients have benign, peripheral (otological) causes for their symptoms. Patients
      with potentially serious central (neurological) problems are usually identified
      on history and examination. Many common causes of vertigo, such as benign
      positional vertigo and migraine, can be successfully diagnosed and treated
      without expensive investigations or referral. Exercise therapy, rather than
      vestibular suppressant medication, should be the mainstay of treatment for
      patients with chronic vertigo due to "uncompensated" vestibular lesions.

PMID- 10901778
TI  - Prostate cancer testing.

PMID- 10901779
TI  - Survival of patients with colorectal cancer detected by a community screening
      program.

PMID- 10901781
TI  - !nform test kits distributed with the MJA.

PMID- 10901780
TI  - Safer use of NSAIDs in Australia.

PMID- 10901782
TI  - !nform test kits distributed with the MJA.

PMID- 10901783
TI  - !nform test kits distributed with the MJA.

PMID- 10901784
TI  - [Microbial infection documented on admission to the intensive care unit for post
      chemotherapy neutropenia after empiric antibiotic therapy].
AB  - OBJECTIVE: The purpose of this study was to determine whether a systematic
      strategy of multiple microbiological samples for all adult patients with
      neutropenia admitted to an intensive care unit could document sepsis despite
      prior empiric antibiotic therapy. PATIENTS AND METHODS: All adults admitted to
      the intensive care unit with chemotherapy-induced neutropenia (WBC < 500/mm3)
      were included in the study. Microbiological samples were systematically obtained
      in all patients: 6 blood, 1 stool, 1 urine, 1 nasal swab. Data were analyzed for
      54 consecutive patients: 22 men, 32 women, 42 with hematology diseases and 12
      with solid tumors, mean age 46.6 +/- 14.4 years. Assessment of disease severity
      showed: simplified gravity index = 256 +/- 17; organ system failure score on day
      1 = 2.42 +/- 1.1; 26 cases of septic shock among 47 cases of sepsis. Mortality
      was 50%. Within 48 h, bronchioalveolar lavage samples were obtained in 48
      patients, and there were 12 spinal taps, 3 laparotomies, 3 skin biopsies and 6
      sinus punctures. RESULTS: A microorganism was isolated in 39 patients (70%): 12
      Gram negative, 12 Gram positive, 11 mycoses, 3 cases of herpes. Positive cultures
      were found for 31 blood, 1 bronchioalveolar lavage, 2 surgical, 5 serous and 22
      oral or digestive tract samples. Documented microbial infection did not have
      prognostic value. Septic shock at admission was predictive of poor outcome.
      DISCUSSION: Despite prior antibiotic therapy in 46 patients, with a theoretically
      active drug in 37 cases, a systematic strategy of multiple deep samples increased
      the number of documented cases of infection in neutropenic patients. Oral and
      digestive tract infections predominated despite selective decontamination of the
      digestive tract.

PMID- 10901785
TI  - [Evaluation of inpatient satisfaction. Comparison of different survey methods].
AB  - OBJECTIVES: To assess the impact of patient satisfaction survey method on
      response rate, data quality and satisfaction. PATIENTS AND METHODS: Four modes of
      data collection were assessed during a randomized trial that included 400
      inpatients discharged from a teaching hospital. RESULTS: The response rate was
      58% within the mail survey group (72% with follow-up letter) versus 73% and 81%
      within the home and telephone interview group (p < 0.01). 69% of the mailed
      questionnaires contained no missing values versus 94% and 96% for home and
      telephone interview modes (p < 0.01). The global satisfaction scale score was
      greater within the mail survey groups (8.1/10 without follow-up letter and 7.9
      with follow-up letter) than within the telephone interview group (7.8) and the
      face to face interview group (7.3), (p < 0.05). CONCLUSION: Mail survey with
      follow-up letter constitutes an operational method despite lower data quality and
      overestimation of patients' satisfaction scores.

PMID- 10901786
TI  - [Aneurysm of the duodeno-pancreatic arcades. Diagnostic imagery and therapeutic
      indications].
AB  - BACKGROUND: Aneurysms of the duodenopancreatic arcades account for 2 to 3% of all
      aneurysms of the digestive arteries. Mortality is high due to the risk of rupture
      and the difficult diagnostic situation. CASE REPORTS: The first case involved a
      short wide collar aneurysm implanted on the first centimeter of the superior
      mesenteric artery, associated with tight stenosis of the celiac trunk. The
      patient complained of diffuse abdominal pain and was treated surgically. In the
      second case, there was a false aneurysm of the gastroduodenal artery which
      developed a few months after acute biliary pancreatitis. The aneurysm was treated
      by exclusion using a transcutaneously delivered endovascular coil prosthesis.
      CONCLUSION: These cases illustrate the importance of imaging (magnetic resonance
      angiography) both for diagnosis and treatment monitoring, allowing early care
      with very limited morbidity and mortality.

PMID- 10901787
TI  - [Cystic dystrophy of an aberrant pancreas. Surgery after failure of medical
      therapy].
AB  - BACKGROUND: Cystic dystrophy of aberrant pancreas, characterized by cystic
      formations in ectopic pancreatic tissue, produces variable signs. Treatment is
      difficult. CASE REPORT: Our patient presented signs of acute pancreatitis and
      angiocholitis due to cystic dystrophy of an aberrant pancreas situated in the
      duodenal wall associated with chronic alcoholic pancreatitis. Prolonged medical
      treatment was unsuccessful. Duodenopancreatectomy with preservation of the tail
      led to complete regression of the clinical signs. DISCUSSION: Signs of cystic
      dystrophy of an aberrant pancreas vary greatly. Diagnosis is generally
      established on the basis of echoendoscopic findings. After failure of medical
      treatment, duodenopancreatectomy with preservation of the tail could be the most
      appropriate surgical treatment, hypothesizing that the disorders result from
      obstruction of the Wirsung and the lower main bile ducts.

PMID- 10901788
TI  - [An unrecognized cause of camptocormia: proximal myotonic myopathy].
AB  - BACKGROUND: The underlying cause of camptocormia, a common condition in adults
      consisting of forward flexion of the trunk both in stance and gait, is often
      unrecognized, attributed by some to primary late-onset myopathy. CASE REPORTS:
      Two patients progressively developed camptocormia. The cause was identified as a
      relatively new disease, proximal myotonic myopathy. DISCUSSION: The diagnosis of
      proximal myotonic myopathy is based on clinical findings: myalgia and diffuse
      pain, gait disorders and progressive weakness of proximal muscles, electrical
      myotonia, cataracte in some cases, elevated gamma glutamyltranspeptidases. The
      disease is transmitted by autosomal dominant inheritance. This condition should
      be entertained as a possible cause in patients presenting an apparently primary
      camptocormic syndrome.

PMID- 10901789
TI  - [Survey of urinary incontinence in a hospital caregiver population].

PMID- 10901790
TI  - [An uncommon cold: Lemierre syndrome].

PMID- 10901791
TI  - [Erythema nodosum in cat scratch disease].

PMID- 10901792
TI  - [Drug prescriptions: an epidemiological survey of French general practitioners].

PMID- 10901793
TI  - [Piercing: health education or medicalization?].
AB  - In Europe, the piercing mode has naturally been associated with specific
      complications raising an important public health problem. The debate on the role
      physicians should play requires a careful analysis of the ethical issues
      involved. Specifically, should the piercing be done in a medical setting? This
      question is raised because, when performed under ideal conditions, the act of
      piercing requires a certain degree of medical competency: history taking,
      asepsia, technical procedure (hemostasis), anesthesia.... However, mandatory
      medicalization would not, in our opinion, appear to be desirable since we are
      dealing with a social rite which lies outside the domain of specific medical
      care. Nevertheless, although we do not advocate systematic medicalization, we do
      believe that medicine should play a role, in terms of public health, in this
      emerging practice. We discuss the modalities of a health education dialogue which
      could be established with professional practicing piercing.

PMID- 10901794
TI  - [Modafinil (Midiodal): wakefulness stimulant in narcoleptic patients].

PMID- 10901795
TI  - [On carcinomatous meningitis secondary to breast cancer].

PMID- 10901796
TI  - [Human T-lymphotropic virus type I (HTLV-I): risk of transmission with
      transfusion].
AB  - PATHOGENIC ROLE: The human T-lymphotropic virus type I (HTLV-I), the first human
      retrovirus discovered, is the etiologic agent of adult T-cell leukemia/lymphoma
      (ATL) and of HTLV-I associated myelopathy or tropical spastic paraparesis
      (HAM/TSP) and has a widespread but uneven worldwide distribution. HTLV-I has a
      high seroprevalence in Southern Japan, the Caribbean basin and Sub-Sahara Africa.
      Blood transfusion, intravenous drug use, breast feeding and sexual contacts are
      major routes of contamination. IMPLICATIONS FOR BLOOD TRANSFUSION: The screening
      of blood donors for antibody to HTLV-I became systematic in 1989 in French West
      Indies and in 1991 in Continental France. This review deals with the
      transfusional implications of the HTLV-I, which belongs to the group of the blood
      borne viruses: the prevalence of transfusion-linked HTLV-I infection before the
      implementation of the specific preventive measures, the parameters influencing
      the risk of transfusional contamination (the type of blood products, the age of
      the blood product with regards to its collection date, the proviral load of the
      blood donor), the prognosis of HTLV-I infection in patients contaminated by
      transfusion, the prophylactic strategies of transfusion contamination and the
      residual risk of infection through HTLV-I-infected risk blood products.

PMID- 10901797
TI  - [Clinical evaluation of female urinary incontinence].
AB  - EXAMINATION: Clinical evaluation of stress and urge incontinence is always
      necessary before therapeutic decisions. Full bladder examination may reveal
      stress incontinence during cough when cervico-urethral hypermobility is
      suspected, and leak during Vasalva manoeuvre when incontinence is due to
      intrinsic sphincter deficiency. OBJECTIVE SCORES: Pad test objectives the
      quantitative importance of incontinence. Symptom scores allow intra and inter
      individual comparisons. Psychosocial implications are studied with specific
      quality of life scales. They allow better therapeutic strategies in the
      management of urge and stress urinary incontinence. Objective evaluation of the
      different treatments and medico-economic approach of incontinence are thus
      possible.

PMID- 10901798
TI  - [Role of MRI in the diagnosis of breast diseases].
AB  - ADVANTAGES AND LIMITATIONS: Magnetic resonance imaging of the breast is probably
      the most sensitive method for detecting or ruling out breast disease. It is
      however not as specific as expected. TECHNIQUE: All examinations are performed
      with and without gadolinium intravenous administration, excepted in the case of
      silicone implant reconstruction mammoplasty. Dynamic contrast-enhanced MRI
      sequences are necessary with a permanent balance between temporal resolution,
      spatial resolution, and signal. MRI of the breast is not indicated as a routine
      examination in a screening program, neither to improve the specificity of infra
      clinic lesions, nor in simply dense breasts without any known risk factor or in
      circumscribed masses. INDICATIONS: MRI is best used to improved the sensitivity
      of mammography and sonography in selected patients. The selected indications are:
      evaluation of the volume and extension of breast lesions evaluation of the
      therapeutic response after chemotherapy, and detection or exclusion of the local
      recurrence in patients with breast conservation therapy. PERSPECTIVES: The future
      indications and perspectives of MRI include interventional breast radiology (MRI
      guided core biopsy), and thermocoagulation therapy. It may be interesting for the
      evaluation of patients with contrast enhanced MRI lesions with normal mammography
      and sonography, and also in woman with a genetically defined high breast cancer
      risk.

PMID- 10901799
TI  - [Acquired epulis in an adult].

PMID- 10901800
TI  - HIV/AIDS debate--time for a truce.

PMID- 10901801
TI  - Legal assistance with dying in South Africa.

PMID- 10901803
TI  - Children's Liver Disease Foundation

PMID- 10901802
TI  - Technology in health care--blessing or curse?

PMID- 10901804
TI  - HIV-positive test results.

PMID- 10901805
TI  - Academic medicine in South Africa.

PMID- 10901806
TI  - Bowel injury following insertion of tension-free vaginal tape.

PMID- 10901808
TI  - Should gay men donate blood?

PMID- 10901807
TI  - HIV surveillance results--little grounds for optimism yet.

PMID- 10901809
TI  - Let them eat (just so much) cake.

PMID- 10901810
TI  - Western Cape MEC toughens up on TB.

PMID- 10901811
TI  - Rural healers teach themselves.

PMID- 10901812
TI  - AIDS management options for SA.

PMID- 10901813
TI  - Mounting pressure on AIDS drug manufactures.

PMID- 10901814
TI  - HIV infection, tuberculosis and non-tuberculous mycobacteria.

PMID- 10901815
TI  - Should the condom come with a health warning?

PMID- 10901816
TI  - Postmodernism, the law, and ethical dilemmas in medicine.

PMID- 10901817
TI  - Superior sagittal sinus thrombosis.

PMID- 10901818
TI  - Guidelines for the management of chronic asthma in children and adults.

PMID- 10901819
TI  - Evaluation of a World Health Organisation colour scale for detection of anaemia
      in a haematology clinic.

PMID- 10901820
TI  - Acoustic trauma--a case report.

PMID- 10901821
TI  - Infant mortality in Soweto--estimates from the birth to ten study using the
      'previous birth' technique.

PMID- 10901822
TI  - AT1 receptor blockers--cost-effectiveness within the South African context.
AB  - OBJECTIVES: Hypertension is a leading chronic disease in South Africa,
      Significant mortality results from this condition and from stroke and ischaemic
      heart disease in which hypertension plays a major role. The objective of this
      study was to evaluate the evidence for the clinically effective and cost
      effective treatment of hypertension, given that the clinician has decided to
      administer an AT1 receptor blocker. METHODOLOGY: A cost-effectiveness analysis
      was undertaken from the perspective of the funder of health care in the private
      sector. A predetermined protocol defined the study scope, the comparators
      (candesartan, losartan, valsartan and irbesartan) and the inclusion criteria for
      peer-reviewed data. Data for the clinical efficacy of the comparators, measured
      as the reduction (mmHg) in sitting diastolic blood pressure (SDBP) achieved, were
      extracted, statistically assessed and reported. The combinability of the data
      from different clinical trials was confirmed using analyses of variance. A
      pharmacoeconomic model was developed by combining these clinical results with
      South African retail prices and testing the results at a 95% confidence level.
      RESULTS: Significant difference in clinical effectiveness was found among the
      comparators, with the following mean reductions in SDBP observed: candesartan
      10.57, irbesartan 9.07, losartan 8.89 and valsartan 7.11 mmHg. Candesartan was
      found to be significantly more effective than losartan. Valsartan was found to be
      less effective than the other 3 comparators. No significant difference was found
      between irbesartan and either candesartan or losartan. The reduction in SDBP per
      R100 spent indicated that candesartan was more cost-effective than the other
      comparators, among which there were no significant differences. Incremental
      savings of R5.0 million annually could be achieved by the funders of private
      health care for every 100,000 successfully treated patients using candesartan.
      CONCLUSION: Significant differences exist in both the clinical and cost
      effectiveness measures used in this study for the comparators. The findings from
      the analysis will be valuable in decision-making processes for both the funders
      and providers of health care. This analysis can be enhanced further by the
      inclusion of additional clinical benefits and long-term health outcomes when the
      relevant data become available.

PMID- 10901824
TI  - Basic resuscitation--knowledge and skills of full-time medical practitioners at
      public hospitals in northern province.
AB  - OBJECTIVES: To establish the level of knowledge and skill in basic resuscitation
      among medical practitioners and to determine the differences in characteristics
      between those with and those without knowledge and skills. DESIGN: Cross
      sectional study. SETTING: Public hospitals in Northern Province. SUBJECTS: All
      the doctors in full-time employment, except interns and those in full-time
      administration. OUTCOME MEASURES: Practice on manikins using structured
      interview/evaluation sheet. RESULTS: Of 152 participants, 7 (4.6%) scored 80% and
      above and 37 (24.3%) scored 50% and above. The medical practitioners who
      performed better were younger and more likely to have received undergraduate and
      postgraduate resuscitation training, and resuscitation training within the last 2
      years. The country of qualification, sex, postgraduate qualification, frequency
      of continuing medical education and past experience of resuscitating cardiac
      arrest patients were not associated with a performance on the evaluation.
      CONCLUSION: Medical practitioner skills and knowledge of basic resuscitation were
      poor and resuscitation experience without training was not found to be
      beneficial. It is therefore recommended that formal training in resuscitation be
      mandatory at undergraduate and postgraduate level, with refresher courses held
      every 2 years.

PMID- 10901823
TI  - Ethics in the practice of psychiatry in South Africa.
AB  - OBJECTIVE: To determine attitudes with regard to ethics in the practice of
      psychiatry in South Africa. DESIGN: Cross-sectional survey. METHOD: The study
      utilised clinical vignettes, with gender and race of the patient as potential
      modifying variables in diagnosis and management. Open-ended questions pertaining
      to potential abuses were included. SETTING AND SUBJECTS: Questionnaires were
      mailed to all practising psychiatrists in South Africa in 1993 and 1994. OUTCOME
      MEASURES: Responses to questionnaire. RESULTS: A 40% response rate was obtained
      (N = 73). Patient race and gender did not influence diagnosis or have a marked
      impact on the prescription of treatment. Pressure from the patient's family on
      the psychiatrist did alter case management, as did the psychiatrist's age and
      gender in some instances. Racial discrimination, sexual misconduct and economic
      abuses were the most frequently cited areas of observed abuse. CONCLUSION: The
      development of an ethical framework for the practice of psychiatry in South
      Africa would appear to be of critical importance.

PMID- 10901825
TI  - Respiratory syncytial virus infection in children hospitalised with acute lower
      respiratory tract infection.
AB  - BACKGROUND: Data are lacking on respiratory syncytial virus. (RSV) respiratory
      tract infections in children from developing countries. OBJECTIVE: To determine
      the importance of RSV as a cause of acute lower respiratory tract infection
      (ALRTI) in Cape Town children. METHODS: Children younger than 2 years of age
      admitted to hospital with ALRTI over a 15-month period from 1 June 1995 to 31
      August 1996 were studied prospectively. Sociodemographic data, risk factors for
      severe RSV disease, clinical signs, diagnosis and hospital course were
      documented. A nasopharyngeal aspirate (NPA) for detection of RSV by enzyme
      immunoassay (EIA) was obtained in all cases. The NPA of every fifth child was
      sent for viral culture. RESULTS: A total of 1,288 patients (60% male, 40% female)
      with a median age (25th-75th percentile) of 6 months (2-11 months) was enrolled;
      32.4 had one or more risk factors for severe RSV infection. Pneumonia was
      diagnosed in 62.2%, bronchiolitis in 20.6%, laryngotracheobronchitis (LTB) in 8%
      and other respiratory illnesses in 9.2%. Mild disease, requiring admission to an
      overnight ward, was documented in 38.1%, while 48.9% and 13% respectively had
      moderate and severe disease requiring admission to a general ward and intensive
      care unit (ICU). Supplemental oxygen and mechanical ventilation were required by
      68.9% and 8.5% of patients, respectively. The median duration of hospital stay
      was 5 days (range 1-10 days). RSV EIA was positive in 16.4% of cases, and there
      was no difference in detection rates according to diagnosis. Viral culture
      performed in 162 of the 1,288 study patients (12.6%) grew RSV in 11.7% of cases,
      adenovirus in 3.7%, para-influenza virus type 3 in 2.5% and influenza B virus in
      0.6%. Patients who tested RSV EIA-positive did not significantly differ from
      those who tested negative with regard to demographic variables, clinical
      diagnoses, risk factors for RSV or length of hospitalisation. The only
      significant difference noted was the presence of hyperinflation, which occurred
      in 70.1% of EIA-positive patients compared with 57.1% of those testing negative
      (P = 0.0005). The mortality rate (2%) was similar for both groups. CONCLUSION:
      This study indicates that RSV is an important cause of hospitalisation in infants
      and young children with ALRTI. Distinguishing RSV from other ALRTIs is difficult
      because of similarity in clinical presentation among children.

PMID- 10901826
TI  - Meningococcal disease in South African goldmines--epidemiology and strategies for
      control.
AB  - OBJECTIVES: To describe the epidemiology of meningococcal disease in South
      African goldmines and to suggest strategies for the prevention and control of
      further outbreaks. DESIGN: We prospectively investigated a meningococcal outbreak
      that occurred in 1996 and describe the control measures that were implemented. In
      addition, we conducted a retrospective analysis of routinely collected data on
      meningococcal disease in these mines from 1972 to 1996. SETTING: Four goldmines
      in Gauteng, employing 30,000 workers who live in hostels. SUBJECTS: All cases of
      meningococcal disease at the mine hospital. RESULTS: Between 1972 and 1976, 588
      cases were diagnosed, with peaks in 1972 (203 cases, 727/100,000) and 1975 (147
      cases, 564/100,000). Since 1978 less than 5 cases have been reported in most
      years, but smaller outbreaks occurred in 1990 (30 cases, 89/100,000) and 1996 (14
      cases, 50/100,000). The 1996 outbreak (group A, clone I-1) was part of a larger
      outbreak in Gauteng that originated in Mozambique and began in one mine in July
      1996, after which a mass vaccination campaign was implemented. This was followed
      by a smaller outbreak among non-vaccinated workers at an adjacent mine. Five
      patients were new recruits. CONCLUSIONS: Despite a dramatic reduction in
      meningococcal disease over the last 25 years due mainly to changes in the work
      force, there are still outbreaks in this community. Those most at risk are young
      men who are new to the industry. Suggestions for prevention include effective
      surveillance, routine vaccination of new recruits and a rapid response to
      outbreaks, with mass vaccination and provision of chemoprophylaxis to close
      contacts.

PMID- 10901827
TI  - An investigation into puerperal psychoses in black women admitted to Baragwanath
      Hospital.
AB  - OBJECTIVES: Puerperal psychosis was studied in black African women at Baragwanath
      Hospital in Johannesburg. DESIGN: A retrospective study analysed the clinical
      notes of 314 cases of puerperal psychosis seen over previous years. A prospective
      study researched 67 cases of puerperal psychosis referred during a full calendar
      year. A control group of 98 patients was matched with the prospective study
      patients for age, marital status, parity and month of delivery. RESULTS: The
      incidence (2-3 cases per 1,000 births), onset and pattern of illness are all
      remarkably similar to that described in the international literature. Confirmed
      risk factors were a primiparous patient; a family history of psychiatric illness;
      and a personal psychiatric history, particularly a history of mania. Additional
      risk factors found in this study were substance dependence; a medical illness;
      the season of the year; a male child; and psychosocial stress including need for
      intensive medical care for the baby or death of the baby. CONCLUSION: The
      conclusion reached is that the puerperal psychoses are undifferentiated
      psychoses, usually mood disorders, showing some special symptomatology, and are
      precipitated in constitutionally predisposed patients by the physiological
      factors of the involutionary period.

PMID- 10901828
TI  - Guideline for the management of chronic asthma in children--2000 update. Allergy
      Society of South Africa Working Group.
AB  - OBJECTIVE: To increase awareness of asthma and diagnose asthma early in children.
      To make recommendations regarding management of chronic childhood asthma in a
      country with diverse cultural, socio-economic and educational characteristics.
      The guideline should be used by health professionals involved in the treatment of
      asthma at all levels of care. OPTIONS: Various management options were
      considered. Ideal treatment includes use of the new generation inhaled
      corticosteroids (fluticasone, budesonide), housedust mite intervention for asthma
      control using impermeable covers for pillows and mattresses, and if needed use of
      inhaled long-acting beta 2 agonists (LABAs) and leukotriene receptor antagonists
      (LRAs). Alternative therapeutic approaches for situations where resources are
      limited include simple housedust mite control measures (e.g. airing mattresses
      and bedding), avoidance of exposure to passive smoking, use of lower doses of
      beclomethasone than recommended by other guideline documents and/or sustained
      release (SR) theophylline as preventer treatment and use of plastic bottles as
      cheap spacer devices. OUTCOMES: The main potential outcomes considered were: to
      reduce morbidity and mortality by correct diagnosis of asthma, to achieve the
      best quality of life for the child with asthma, to minimise side-effects from
      medication and to prevent development of permanently abnormal lung function.
      EVIDENCE: Current international guideline documents for diagnosis and management
      of childhood asthma were evaluated. Clinical studies before 1998 pertaining to
      the various aspects of management of childhood asthma were reviewed, including
      controlled studies on the use of inhaled corticosteroids in children with asthma,
      randomised controlled trials on the use of LRAs and two studies evaluating the
      efficacy of LABAs. Current data on the anti-inflammatory effects of SR
      theophylline were also reviewed as well as a randomised controlled trial on the
      benefits of SR theophylline as adjunct treatment in childhood asthma. The benefit
      of simple spacer devices, based on well-conducted local studies (published in an
      international peer-reviewed journal) was also considered. VALUES: The South
      African Childhood Asthma Working Group (SACAWG) committee members, appointed by
      the Allergy Society of South Africa (ALLSA), were selected to represent the
      interests of health professionals involved in the care of childhood asthma and to
      co-opt other colleagues with expertise relevant to the guideline. The committee
      was divided into six task groups headed by a chairperson--each task group had to
      review critically the previous SACAWG guideline (for deficiencies and obstacles
      to implementation), review current trends in asthma management (evidence-based
      where available) and submit proposals and recommendations to their respective
      chairperson. The chairperson then compiled a report for discussion by the SACAWG
      executive committee. The executive group convened a meeting to discuss the
      recommendations and obtain consensus. An editorial board was appointed to compile
      the final report. Cultural factors, patient preferences, cost, availability and
      education were considered important. BENEFITS, HARMS AND COSTS: Proper treatment
      should enable most children with asthma to lead normal or near-normal lives. The
      guideline could be implementable at all levels of care. The risk of systemic
      effects due to inhaled corticosteroids should be minimised in children with mild
      to moderate persistent asthma (risk of systemic effects is more likely at daily
      beclomethasone doses exceeding 400 micrograms or the equivalent dose of other
      inhaled corticosteroids). Promotion of simple environmental control measures and
      use of inhaled beclomethasone and/or SR theophylline should make treatment more
      widely available and more affordable and improve adherence to treatment.
      Alternative cheap plastic bottle spacer devices will increase availability and
      assist with overcoming the problem of incorrect inha

PMID- 10901829
TI  - Guideline for the management of chronic asthma in adults--2000 update. South
      African Pulmonology Society Adult Asthma Working Group.
AB  - OBJECTIVE: To make recommendations for the cost-effective management of asthma
      incorporating recent advances in the understanding and treatment of asthma since
      the last guideline statement in 1992. The guideline is applicable to adults and
      children over 12 years of age. OPTIONS: Asthma should be graded according to
      standard severity criteria. The principle of 'hit early, hit hard' with
      corticosteroids to achieve rapid control is encouraged; thereafter treatment
      should be tailed down to the lowest dose of corticosteroids that maintains the
      aims of asthma treatment. OUTCOMES: The aims of asthma management should be
      achieved; these include: (i) avoidance of causative and trigger factors; (ii)
      abolition of symptoms and ability to lead a normal lifestyle; (iii) restoration
      of normal (or best possible) lung function; (iv) reduction of the risk of severe
      attacks; and (v) optimisation of treatment with minimal side-effects. EVIDENCE:
      Based on a selective review of randomised, controlled studies to support an
      evidence-based approach to treatment. BENEFITS, HARMS AND COSTS: Appropriate
      management of asthma should lead to a reduction in morbidity and mortality of
      asthma and a consequent reduction in cost of asthma care. Side-effects of
      corticosteroids are placed in perspective together with a strategy to minimise
      these effects. RECOMMENDATIONS: Asthma should be managed with inhaled
      corticosteroids as the most important anti-inflammatory treatment, except in the
      case of mild intermittent asthma which may be treated with beta 2 agonists on a
      pro re nata (prn) basis. It is preferable to add long-acting beta 2 agonists to
      low-dose inhaled corticosteroids before increasing corticosteroids. Leukotriene
      receptor antagonists are currently recommended for use in combination with
      inhaled corticosteroids pending further data on their long-term benefits.
      Differentiation of asthma from chronic obstructive pulmonary disease (COPD) is
      important. Early referral to a pulmonologist in difficult cases is encouraged.
      VALIDATION: Endorsed by the South African Pulmonology Society, the Allergy
      Society of South Africa and the South African Medical Association. The guideline
      is compatible with those of other international societies.

PMID- 10901830
TI  - [Psychotropic drug use and associated factors in a professional environment].
AB  - Drug use has been evaluated from a study conducted in a large french firm during
      1992. The main objective of this study was to estimate prevalence of depressive
      and anxiety disorders and define professional factors. Psychotropic drug use has
      been measured by the percentage of subjects reporting their regular or occasional
      use during the 12 last months. Self-reported resort to medical system and sick
      leaves for psychiatric reason has been also examined during the same period.
      Lifetime and 12-month prevalence of depressive and anxiety disorders have been
      measured with a standardized questionnaire (CIDI, Composite International
      Diagnostic Interview) according to the criteria for the DSM III-R. A randomized
      sample of 540 subjects was obtained from two stages procedure. In first, a
      screening stage on 10,000 employees with the 12-items General Health
      Questionnaire (GHQ-12). The screened population was stratified on the global
      score GHQ-12 (> or = 3 and < 3). 270 subjects were randomized in each group and
      interviewed with CIDI. Occasional and regular psychotropic drug use is
      respectively 41.1% and 6.8% in women, 16.7% and 3.4% in men. It is much higher
      after 45 years (regular use: 18.8% in women and 7.6% in men). Only 6% of men and
      7% of women with depressive disorders use regularly psychotropic drugs, the
      occasional use is 27% and 73%. In one third of the cases use regularly
      psychotropic drug.

PMID- 10901831
TI  - [Alzheimer's disease and informed consent of incapacitated people: propositions
      aimed at improving the procedure].
AB  - Ethical considerations must be given priority when deciding whether or not to
      include an Alzheimer's Disease patient in a study leading to direct individual
      benefits. Although the law applies to ethics, the Huriet-Serusclat law was
      nevertheless written in the spirit of the major ethical declarations of the last
      50 years (Nurenberg, Helsinki, Tokyo...) in order to protect patients from
      abusive decisions, whether these decisions were for or against the patient
      receiving treatment. This paper describes an incident during a phase II trial
      involving patients with Alzheimer's Disease. Four incapacitated patients
      protected by guardianship had given their informed consent to take part in the
      study. Their participation required that the informed consent be signed by the
      guardian as well. By misunderstanding of the law, the guardian transmitted the
      decision to the guardianship judge. Surprisingly, the guardianship judge refused
      permission for all patients to take part in this therapeutic trial against the
      wishes of the patients. Even more surprisingly, it appeared clearly that this
      judge was not thoroughly informed of each detail of the law. Prevention of this
      kind of situation might require modifications of the responsibilities of the
      CCPPRB. It is suggested that before the start of a study the CCPPRB should give a
      precise definition of the way in which incapacitated persons should be treated.

PMID- 10901832
TI  - [Organization and achievement of a training for ICD-10 rating. The experience of
      La Verriere Psychiatric Hospital].
AB  - Referring to an International Classification of Mental Health and Behavioural
      Disorders is a way for psychiatrists to use a common language. The publication of
      the ICD-10 Chapter V made this possible. A note from the French Ministry of
      Health (14 January 1993) made official the use of the ICD-10th Revision in order
      to complete the psychiatric sector patient files. During 1992, in the La Verriere
      Psychiatric Hospital, all doctors, psychologists and nurses get trained in the
      use of the ICD-10. Twelve video inpatient cases were rated and discussed
      following the ICD-10 criteria. This paper reports on this experience.

PMID- 10901833
TI  - [A survey of private practice psychiatrist's training and activity in activity in
      Aquitaine, France, in 1993].
AB  - This study was conducted to gather information regarding the current professional
      activities of French private practice psychiatrists. METHOD: A mail survey was
      carried out in an attempt to find more about the characteristics of the 380
      private practice psychiatrists in Aquitaine (south west France) in 1993. Data are
      reported in terms of psychiatrist's characteristics (demographics, training and
      practice activities), patient characteristics and trends in treatment modalities.
      RESULTS: There was a good response rate (55%), and this enabled us to
      statistically analyze the data to determine profiles of activities. For the
      respondents in this survey, the median age is 45 years and 30.7% of respondents
      are women. The portion of responders reporting a qualification in Neuropsychiatry
      versus Psychiatry, is low (1/7). The patients seen in private practice are
      generally young females with anxiety and affective disorders. An important
      feature was the trend for psychotherapy training and practice. Psychoanalytically
      oriented and individual psychotherapy were predominant over other forms of
      psychotherapy. Half of the psychiatrists reported using pharmacotherapy in
      combination with psychotherapy. There are only little differences in the practice
      of young and female psychiatrists. CONCLUSION: The impact of psychodynamic
      theories on the training of French private practice psychiatrists is still very
      important. Interestingly, these same psychiatrists seem to use an eclectic
      approach to their practice of psychiatry; about half of the respondents report
      using pharmacological treatments in combination with psychoanalytically oriented
      psychotherapy.

PMID- 10901834
TI  - [French version of the video structured interview designed for type A behavior
      pattern assessment].
AB  - The current controversy on the predictive value of the Type A Behavior Pattern
      (TABP) as a coronary risk factor brought into a reconsideration of the assessment
      methods of this pattern. The Video Structured Interview (VSI) is a scoring method
      of TABP by a trained investigator, consisting of a rating scale based both on the
      content of the answers and on the psychomotor signs, with regard to the two main
      components of the TABP: sense of time urgency and hostility. The VSI appears a
      more objective instrument than self-assessment questionnaires, avoiding the bias
      of denial, a coping mechanism widely used by type A subjects. The VSI proved more
      sensitive and more specific than the self-assessment methods or the structured
      interview (SI), the initial instrument aimed to assess TABP among coronary risk
      patients in american populations. We here present the french version of the VSI,
      the technical modes of the interview and the principles of this scoring method,
      in order to introduce in France its use in further studies related with coronary
      risk factors.

PMID- 10901835
TI  - [Plasma, red cell, and cerebrospinal fluid folate in Alzheimer's disease].
AB  - This study compares plasma, red cell, and cerebrospinal fluid (CSF) folate levels
      in subjects with mild or moderate Alzheimer's disease (AD) of senile onset and in
      non-demented control subjects. Twelve subjects with mild or moderate (Folstein's
      Mini-Mental-State-MMS--between 10 and 23) AD (DSM3 R criteria) and 12 control
      subjects without dementia and with MMS above 23 were included. To avoid any
      change in plasma folate levels due to dehydration, all dehydrated subjects were
      excluded. Were also excluded all subjects obviously suffering from malnutrition
      or alcoholism, or taking drugs likely to interfere with folate metabolism.
      Changes in folate levels due to posture or prolonged venous occlusion were
      carefully avoided. Patients with AD were 5 males and 7 females aged (Mean +/- SD)
      80.2 +/- 5.7 years, MMS 14.8 +/- 2.6; controls were 7 males and 5 females aged
      78.9 +/- 7.2 y, MMS 28.3 +/- 1.5. The two groups were not statistically different
      for these variables, except for the MMS. Plasma folate levels were lower (p <
      0.006) in patients with AD (4.5 +/- 1.5 micrograms/l) compared with controls (7
      +/- 2.2 micrograms/l). Red cell folate levels were lower (p < 0.007) in patients
      with AD (183.7 +/- 91.1 micrograms/l) compared with controls (300.4 +/- 96.1
      micrograms/l). CSF folate levels were lower in AD (18.9 +/- 9.7 micrograms/l)
      than in controls (21.9 +/- 8.2 micrograms/l) but the difference was not
      statistically significant (p > 0.05). Our results indicate poorer nutrition in
      patients with AD.

PMID- 10901836
TI  - [Neurocognitive subtypes of schizophrenia according to performance at verbal
      fluency tasks].
AB  - There is a general agreement that schizophrenia is an heterogeneous disorder and
      cognitive performances could be an interesting feature in order to allow a better
      description of specific subtypes. The aim of this study was: 1) to describe
      clinical and neuropsychological performances of 45 DSM IV schizophrenic patients
      divided in two groups according to their performances in verbal fluency task; 2)
      to compare each group with the performances of healthy subjects matched for sex,
      age and education. METHOD: The differentiation criteria was the total number of
      words generated during 3 formal and 3 semantic fluency tasks. Data were analysed
      using a disjoint clustering procedure with Euclidean distance. A two cluster
      solution was considered optimal. Cluster S1 includes 21 schizophrenic subjects
      defined as low performer (range: 40-83, mean 66.7). Cluster S2 includes 24
      schizophrenic subjects (range: 87-158, mean 102.8). All schizophrenic patients
      were clinically evaluated with SANS, SAPS and a psychosocial aptitude rating
      scale (PARS). Patients and controls were assessed with the following battery:
      verbal fluency, Trail making test A & B, Stroop test, Brown Peterson paradigm for
      evaluation of working memory. RESULTS: Patients with low verbal fluency had
      significantly higher scores at the SANS and PARS. Furthermore, the low performers
      (cluster S1) were differentiated from those with better performances (cluster S2)
      by significantly poorer results in all neuropsychological tests. Comparison with
      healthy subjects indicated that cluster S1 patients also had significantly poorer
      results in all neuropsychological tests. Relative to their 24 controls cluster S2
      patients performances was lower in all measures excepted in one subscore of the
      Stroop test and in the number of cluster produced. This later result could
      indicate that some capacities for willed intention were preserved in this group
      and that the alteration in verbal fluency performances were better explained by
      impairment of the other cognitive processes. DISCUSSION: These findings point out
      that: 1) use of performance in cognitive executive task such as verbal fluency is
      a possible criteria in order to separate different types of schizophrenic
      patients; 2) in the two groups of schizophrenic subjects, various processes
      defects underline cognitive performances indicating the presence of different
      neurobiological dysfunctioning.

PMID- 10901837
TI  - [Locus of control in alcoholics: comparative study of 64 alcoholics vs 50
      hospitalized patients and 50 normal controls].
AB  - The locus of control is a construct that consists of factors that influence and
      contribute to a person's belief concerning the extent and degree to which he or
      others can influence life events. The study had four purposes. They were to
      examine differences between psychiatric inpatients alcoholics and non alcoholics
      on the internal, chance and powerful others subscales of the French version of
      Levenson's scale, to evaluate differences on these scores between the alcoholics
      who accepted the alcohol program treatment proposed at the admission
      (hospitalization of 15 days with a directive and structured context) and those
      who refused this treatment, to assess the impact of treatment on the Levenson
      scale scores of the alcoholics, and finally to determine whether the Levenson
      scale scores differentiate between treatment successes and failures (evaluated at
      three months). 171 subjects were divided into three groups: 64 patients
      hospitalized in psychiatry for chronic alcoholism (ICD-10 criteria for alcohol
      dependency), 50 patients hospitalized in psychiatry for an other pathology
      (control group) and 57 healthy subjects (normal group). These subjects filled out
      the IPC (Internal, Powerful others, Chance) scale of Levenson, different from the
      I-E (Internal-External) Rotter's scale because it distinguishes two types of
      externality: one imprevisible, the chance, and the other previsible, the powerful
      others. The results showed that the alcoholics as the controls are more external
      than the healthy subjects (Chance and Powerful others subscales). They also
      showed that the alcoholics who refused the alcohol treatment program proposed at
      the admission were more internal than those who accepted. We also found that,
      during the treatment, the alcoholics' scores of Internality increased while their
      scores of externality (Chance and Powerful others) decreased. This decreasing was
      also found with the check inpatients. So these changes would have connections
      with an "hospitalization factor" and wouldn't be due to the alcohol treatment. As
      for the last purpose, there were no significant differences between the initial
      locus of control scores of the successes and those of the failures.

PMID- 10901838
TI  - [The tolerability and efficacy of combined antidepressant therapy: literature
      review].
AB  - There are many pharmacological strategies in order to manage depressed patients
      with treatment resistance. Combined antidepressants therapy is currently
      prescribed, mostly for depressions which resist to a single antidepressant, or to
      another therapeutic, such as electric-convulsive-therapy. Combined treatments are
      usually considered to have a more rapid action than monotherapy, although mainly
      is based on personal experience. It is generally admitted that the better
      efficacy of combined antidepressants therapy with different biochemical
      characteristics is explained by the synergic action of both norepinephrine and
      serotonin systems. The combination treatment of MAOI and tricyclic agents has
      been widely studied, sometimes on hundreds of patients. Numerous studies showed a
      good efficacy, and the toxicity of such an association was exaggerated, thus they
      are nevertheless rarely prescribed. As reversible MAOI-A are now available,
      combination treatment with tricyclic antidepressants is theoretically safer. The
      combination treatment of SSRI and tricyclic antidepressants is more frequently
      reported in the recent literature. Studies analysing such an association are
      however insufficient, and cannot lead to any clear conclusion. The combined
      treatment of mianserin and tricyclic antidepressants have also been quoted, with
      an efficacy that has been confirmed on randomized placebo-controlled studies.
      Resistant depressions are the main indication for combined antidepressants
      therapy. Anxious disorders have recently been considered as interesting new
      indications, such as panic disorder or obsessive compulsive disorder, with or
      without a comorbid mood disorder. In conclusion, controlled studies devoted to
      the analysis of combined antidepressants therapy are relatively few, and do not
      allow to draw any conclusion about their efficacy. Nevertheless, as this type of
      prescription is frequent, scientific evaluation of their specific efficacy is
      needed.

PMID- 10901840
TI  - [Clozapine in the treatment of refractory rapid cycling bipolar disorder].
AB  - A 42 years old man suffering from bipolar disorder I with rapid cycling,
      unresponsive to conventional therapy, was successfully treated with clozapine.
      The plasma clozapine levels were monitored. This case suggests that clozapine
      could be efficient in treating mania and preventing relapse in affective
      disorders. The plasma concentration of clozapine is discussed.

PMID- 10901839
TI  - [Efficacy and withdrawal of clobazam, lorazepam and buspirone in the treatment of
      anxiety disorders].
AB  - This multicentre study was conducted to evaluate the efficacy and consequences of
      progressive or abrupt withdrawal of clobazam in the treatment of Generalized
      Anxiety Disorder in a double blind study in comparison to lorazepam and
      buspirone. 128 outpatients suffering from Generalized Anxiety Disorder according
      to DMS III criteria were included in the study and treated for three weeks. They
      were randomly divided into 4 groups: group 1: 32 patients receiving clobazam,
      abruptly withdrawn and replaced by a placebo; group 2: 29 patients receiving
      clobazam with progressive withdrawal over 3 weeks, clobazam being replaced by a
      placebo; group 3: 33 patients receiving lorazepam with progressive withdrawal
      over 3 weeks, lorazepam being replaced by a placebo; group 4: 34 patients
      receiving buspirone, abruptly withdrawn and replaced by a placebo. The dosages
      were increased progressively during the first week of treatment. At the end of
      this time, the patients received either 30 mg clobazam or 30 mg buspirone or 3 mg
      lorazepam daily. After the first week, the Hamilton Anxiety Rating Scale (HARS)
      showed a significant improvement in clobazam and lorazepam groups but not in
      buspirone group. All the drugs were equally effective after three weeks of
      treatment. The anti-anxiety activity persisted after withdrawal of the studied
      drug in the 4 groups, without any signs of rebound anxiety or withdrawal
      syndrome. No clinically relevant differences were found between the 4 groups
      regarding safety. The side-effects reported were mainly drowsiness in clobazam
      and lorazepam groups, nausea and headache in buspirone group. In conclusion,
      clobazam like lorazepam improved anxiety more quickly than buspirone; after 3
      weeks of therapy, efficacy was comparable with the 3 drugs and persisted after
      treatment discontinuation.

PMID- 10901841
TI  - [The progress of virology at the dawn of the year 2000].

PMID- 10901842
TI  - [Viruses and civilization].
AB  - A few million years ago, when primates moved from the east African forest to the
      savannah, they were already infected with endogenous viruses and occultly
      transmitted them to the prime Homo species. However it was much later with the
      building of the first large cities in Mesopotamia that interhuman viral
      transmission began in earnest. Spreading was further enhanced with the
      organization of the Egyptian, Greek, Roman, and Arab empires around the
      Mediterranean. Discovery of the New World in 1492 led to an unprecedented clash
      of civilizations and the destruction of pre-Columbian Indian civilizations. It
      also led to a rapid spread of viruses across the Atlantic Ocean with the
      emergence of yellow fever and appearance of smallpox and measles throughout the
      world. However the greatest opportunities for worldwide viral development have
      been created by our present, modern civilization. This fact is illustrated by
      epidemic outbreaks of human immunodeficiency virus, Venezuela hemorrhagic fever,
      Rift valley fever virus, and monkey pox virus. Close analysis underscores the
      major role of human intervention in producing these events.

PMID- 10901843
TI  - [Variability and development of viral populations: assessment and implications].
AB  - RNA virus populations consist of complex distributions of closely related but not
      identical genomes known as viral quasi-species. The quasi-species concept
      describes the dynamics of these genomes subjected to a continuous process of
      variation, competition, and selection. Quasi-species dynamics has broad
      implications not only in the understanding of the molecular mechanisms underlying
      adaptation of RNA viruses but also in the design of strategies for control and
      prevention of viral disease. Viral load and genetic heterogeneity have a
      determinant influence on the adaptation of RNA virus to their environment.
      Vaccines designed to control diseases caused by highly variable viruses must
      contain several B and T epitopes to provide an ample and diversified immune
      response. Similarly, antiviral drugs should be used in combination therapy to
      minimize selection of resistant viruses. The theoretical model of quasi-species
      has opened the way for new antiviral therapies based on augmentation of the
      mutation rate during replication of viral RNA. Finally the quasi-species concept
      provides the basis for defining the selective factors that could influence the
      evolution of RNA virus and promote the emergence or reemergence of viral
      diseases.

PMID- 10901844
TI  - [Anthropozoonozes: the species barrier].
AB  - Various animal virus can infect humans with a wide range of clinical
      manifestations from subclinical to fatal. In theory transmission is also possible
      in a number of poorly defined situations. Several examples of interspecific
      contamination in animals and the emergence of new viral infections in animals
      have documented the ability of some viruses to cross the species barrier. The
      barrier concept is based on epidemiological factors lowering the probability of
      exposition to risk and molecular factors limiting or preventing viral replication
      in alien hosts. Although these mechanisms are generally effective, they can fail
      under circumstances. This is notably the case when changes in the ecosystem lead
      to the development of variants able to replicate in different hosts including
      man. An analysis of several mechanisms underlying the species barrier is also
      presented. Some viruses are prevented from entering the organism by the absence
      of suitable receptors, but development is possible if entrance is forced. Other
      viruses can enter but the organism but are unable to complete their developmental
      cycle. Study has shown that these inhibitory mechanisms correspond to
      interactions involving a small number of amino acids. Such a blockage could be
      leaky, especially for RNA viruses with a high mutation rate.

PMID- 10901845
TI  - [Micronutrients and tropical viral infections: one aspect of pathogenic
      complexity in tropical medicine].
AB  - In tropical zones, uncertain living conditions, inadequate food intake, and poor
      medical facilities enhance unnecessary morbidity and mortality especially
      involving infants and young children. In addition to protein-caloric
      malnutrition, deficiencies in essential micronutrients have a specific health
      impact. Such deficiencies can be the direct cause of disease such as vitamin A
      deficiency and blindness or have a promoting effect by compromising immune status
      and increasing susceptibility to and severity of infectious diseases especially
      of viral origin. The promoting effect of micronutrient deficiency plays a
      significant role in measles, rotavirus-related diarrhea, and, to a certain
      extent, progression of HIV infection. Several examples are described to
      illustrate the relationship between tropical viral infection and micronutrients
      including vitamin A, selenium, and various other antioxidants. These examples
      highlight the effect of infectious disease on micronutritional status (vitamin A
      and measles) and the need to develop reliable, practical tools to evaluate the
      relevance and effectiveness of dietary supplementation. In any case, improving
      living conditions and health programs such as the Expanded Vaccination Program
      are required and illustrate a transverse approach for prevention of infectious
      and non-infectious tropical disease. The relationship between micronutrients and
      infection is only one aspect of the multifactorial reality that must be dealt
      with in tropical medicine.

PMID- 10901846
TI  - [Genetic diversity of HIV infection worldwide and its consequences].
AB  - Phylogenetic study of HIV-1 strains from different geographical locations has
      revealed the existence of three separate groups that have been named M, N, and O.
      Most strains involved in the pandemia belong to group M which contains several
      subtypes. Nearly 20 p. 100 of isolates in group M are recombinant with genomic
      components from different subtypes. Some mosaic virus are one-of-a-kind or
      limited to small transmission groups while others are major players in the
      worldwide AIDS epidemic. They are currently called circulating recombinant forms
      (CRFs). Since subtypes or CRFs must be similar over the whole genome, only 9
      subtypes are possible within group M (A, B, C, D, F, G, H, J and K). Viruses E
      and I in the envelope are recombinant. Subtyping is a powerful molecular tool for
      monitoring the evolution of the HIV-1 epidemic. Overall the predominant viral
      forms in the world are subtypes A and C followed by recombinant CRF01-AE
      (formerly subtype E) and CRF02-AG (identical to the IBNG prototype strain in
      Nigeria) and subtype B. The highest degree of genetic diversity in HIV-1 is
      observed in Africa where all subtypes and groups can be observed. The geographic
      distribution of subtypes is subject to constant change. Recombinant forms of the
      virus will continue to appear as long as the different subtypes of HIV-1 continue
      to circulate between continents and recombination continues to occur.

PMID- 10901847
TI  - [Reduction of mother-child transmission of HIV infection in Africa: from clinical
      research to public health programs].
AB  - More and more African women are infected by HIV. As a result the mother-to-child
      transmission (MCT) rate is rising. Various prevention techniques have been
      assessed in randomized clinical trials in Africa but results need to be discussed
      to understand the full implications for prevention programs. To gain insight into
      this issue, we reviewed 11 randomized trials conducted in Africa and several
      other studies from developed countries. Trials using antiretroviral (ARV) drugs
      demonstrated good results for prevention of MCT in the first six months of life
      using abbreviated regimens involving either zidovudine (with or without
      lamivudine) or nevirapine alone. Preliminary results suggest long-term
      effectiveness of zidovudine. Antiseptic and nutritional interventions have
      demonstrated some efficacy in reducing maternal and newborn morbidity and
      mortality but have no effect on MCT rate. Confidential, voluntary HIV screening
      and counseling of pregnant women and short-course ARV treatment during the
      perinatal period associated with alternatives to breast-feeding such as early
      weaning or replacement of breast milk at birth are now the best methods to reduce
      MCT. Prevention of postnatal transmission will require further study in
      particular with regard to effects of different methods of feeding and post
      exposure prophylaxis using ARV drugs in newborns. Management of HIV-infected
      children must remain a high priority. Implementation of currently available
      strategies is now under discussion.

PMID- 10901849
TI  - [HTLV-1 infection in time and space].
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is a member of the Oncoretrovirinae
      family containing several viruses that have been associated with a low incidence
      of leukemia and sarcoma in mammals. Primates are susceptible to viruses of genera
      HTLV (humans) and STLV (other primates). The high degree of homology in genomic
      arrangement of HTLV and STLV is probably due to the existence of a common simian
      ancestor. Most infections are asymptomatic but a few cases exhibit blood
      diseases, e.g., T-lymphoma or T-cell leukemia, or neurologic disease, mainly,
      HTLV-1 associated myelopathy and tropical spastic paraparesia (HAM-TSP). The four
      major modes of viral transmission are vertical transmission from mother to child
      either in utero or, more commonly, during breastfeeding, sexual intercourse,
      blood transfusion, and intravenous drug use. Geographic distribution of HTLV-1
      and its confinement to a few well-defined ecosystems have yet to be explained.
      Diagnosis is now easy and can reduce transmission by intravenous drugs use.
      Development of a vaccine seems possible given the low genetic variability of this
      virus.

PMID- 10901848
TI  - [The HIV/AIDS pandemic: African women at the heart of the control program or the
      difficulties with regard to gender].
AB  - The AIDS pandemia in developing countries forces forth the question of women's
      rights in Africa and underscores their extreme physical and sociocultural
      vulnerability. Experience gained during a program designed to reduce mother-to
      child transmission of HIV in the Ivory Coast highlights the socially imposed and
      therefore intricate nature of differences between men and women and of the
      resulting relationships. Defending a woman's right to know her serologic status
      empowers her in the fight for emancipation but can also make her more fragile by
      undermining support from medical staff and family environment. To prevent the
      risk of outcasting, exclusion, and fragilization, gender must be given greater
      emphasis in planning future programs. Careful consideration must be devoted to
      the special sociocultural factors that affect women in Africa.

PMID- 10901850
TI  - Progress towards the eradication of poliomyelitis globally and in Africa, January
      2000.
AB  - Led by an international partnership including Rotary International, the WHO,
      UNICEF and the Centers for Disease Control and Prevention in the USA, the global
      initiative to eradicate poliomyelitis has made remarkable progress since its
      beginning in 1988. The number of polio cases has decreased from an estimated
      350,000 cases in 1988 to just over 5,000 reported cases in 1999. Following
      successful eradication from the WHO Region of the America's, certified as polio
      free in 1994, wild poliovirus was last reported from the Western Pacific Region
      (including China) in 1997, and from the European Region (including all countries
      of the former Soviet Union) in November 1998. Large parts of Southern and
      Northern Africa and the Middle East are also polio-free. This success is related
      to the implementation of annual nationwide supplemental oral poliovaccine (OPV)
      campaigns in all recently or currently polio-endemic countries, targeting all
      children under 5 years with two doses of OPV. Progress of the initiative is
      monitored by special surveillance systems for all cases of acute flaccid
      paralysis (AFP) in children under 15 years, including virological testing to rule
      out wild poliovirus infection. The initiative currently focuses on a limited
      number of remaining endemic countries in South Asia and Africa, including India,
      Pakistan, Bangladesh, and Nigeria. The initiative is also beginning to be
      successful in several countries affected by conflict situations, such as
      Afghanistan, Sudan (South), Somalia, Democratic Republic of the Congo and Angola.

PMID- 10901851
TI  - [Biohazards due to Orthopoxvirus: should we re-vaccinate against smallpox?].
AB  - Although the WHO declared global smallpox eradication in 1980, the Orthopoxvirus
      remains a source of concern for several reasons. Firstly, stocks of the smallpox
      virus have been preserved for experimental use (at least officially in the USA
      and Russia) so that an escaped isolate could lead to reemergence and spread of
      the disease worldwide. Secondly discontinuation of smallpox vaccination programs
      has led to dwindling acquired immunity in the world population thus raising the
      risk of epidemic extension of several Orthopoxvirus zoonoses (e.g., monkeypox).
      Thirdly stocks of camelpox virus which is very similar to Smallpox virus and was
      intended for biological warfare were discovered during the Gulf War in 1991 and
      pose a potentially serious threat. Finally official stocks of Smallpox virus
      could be stolen and used by bioterrorists. Thus reemergence of Orthopoxvirus
      including smallpox, monkeypox, cowpox, and camelpox is a real danger and
      contingency planning is needed to define prophylactic and therapeutic strategies
      to prevent and/or stop an epidemics. Adverse effects from earlier smallpox
      vaccine (vaccinia) in healthy people or immunocompromised people (congenital or
      acquired as in HIV infected patients) are absolute contraindications to smallpox
      vaccination at this time. Further research is needed to develop new vaccines
      (e.g., attenuated isolates of vaccinia) and effective treatment. This is the only
      valid reasons for postponing planned destruction of remaining Smallpox virus
      stocks.

PMID- 10901852
TI  - [West Nile virus: a migrating arbovirus of current interest].
AB  - West Nile (WN) virus is a common arbovirosis in sub-Saharian Africa. It has
      occasionally caused epidemics or epizootics in horses in Mediterranean regions
      and southern Europe. The virus is transmitted to humans by mosquitoes (primarily
      the Culex species) that are infected by biting viremic birds. Infections in
      humans are usually asymptomatic. Recently, however, a growing number of cases
      involving central nervous system manifestations and deaths have been reported in
      elderly people in Algeria and Romania. Deaths have also been recorded in
      migrating birds in zones where the virus is emerging. An outbreak of WN virus in
      an urban area of North America in 1999 underscored the ability of viruses to
      appear suddenly in unexpected places. Molecular biology techniques are required
      for positive identification of WN virus. Serological tests alone do not allow
      differentiation from other flavivirus in the encephalitis group including
      Japanese encephalitis in Asia and Saint Louis encephalitis in North America.
      Virological monitoring of sentinel birds should provide a better understanding of
      epidemiological factors and of the pathological potential of circulating strains.

PMID- 10901853
TI  - Comments on the epidemiology, pathogenesis and control of dengue.
AB  - Dengue is currently the most important viral disease transmitted to man by
      arthropods, whether measured by the number of cases or number of deaths.
      Prevalence of the disease is highest in tropical Asia, intermediate in tropical
      America, and lowest in tropical Africa. Four distinct dengue viruses have been
      identified. Types 2 and 3 appear to be more pathogenic on the average than types
      1 and 4, but all four can cause severe or fatal dengue syndromes. Infection with
      any of the four viruses confers life-long homotypic, but not heterotypic,
      immunity. Dengue viruses can be transmitted by several mosquito species of the
      genus Aedes, but by far the most common vector is Aedes aegypti. All non-human
      primates that have been tested are susceptible to infection, but none exhibit
      signs of illness. The resulting lack of a suitable experimental host other than
      man has slowed progress in understanding the pathogenesis of severe forms of the
      disease. Controversy continues over the hypothesis that a first dengue infection
      increases the risk of severe disease upon re-infection as well as over the
      principal sites of replication. With regard to replication sites, some authors
      have mentioned cells of the mononuclear phagocyte lineage while others have
      implicated hepatocytes. No vaccine is currently available for dengue. Because the
      principal mosquito vector can use a wide variety of small domestic containers,
      vector control programs have not been highly effective.

PMID- 10901854
TI  - [Epstein-Barr virus and Burkitt's lymphoma].
AB  - Burkitt's lymphoma has the highest incidence of any childhood cancer in
      equatorial Africa. Geographic distribution appears to be related to climatic
      conditions and coincides with areas of endemic malaria. These tumors are
      characterized by reciprocal translocation from chromosome 8 at or near the c-myc
      locus to either the immunoglobulin chain locus on chromosome 14 (80 p. 100 of
      cases) or one of the light chain loci on chromosome 2 or 22. As a result of this
      translocation, transcription of the protooncogene c-myc is activated.
      Deregulation of c-myc could play a major role in onset and development of the
      tumor. Study of Burkitt's lymphoma led to the discovery of the first association
      between viral infection and tumor development in humans. The Epstein-Barr virus
      is contained in all endemic Burkitt's lymphoma cells, thus implicating it as a
      likely etiologic factor. Viral expression is reduced essentially to small non
      coding RNA, non-polyadenilates, and EBERs (10(6) copies per cell) and a nuclear
      protein EBNA1 which is indispensable for maintenance of the Epstein-Barr virus
      genome in infected cells. Expression of EBNA in transgenes leads to lymphoma in
      mice and could play a role in the expression of the c-myc gene involved in
      translocations.

PMID- 10901855
TI  - [Vaccination against hepatitis B virus: current data].
AB  - Infection by hepatitis B virus remains a major health problem in the world
      despite the availability of effective vaccines. Although vaccination programs
      targeting high risk groups have been pushed to their limits, high prevalence
      rates persist especially in endemic zones. More recently mass vaccination
      programs conducted on Taiwan have demonstrated the efficacy of this approach with
      a decrease in the number of chronic hepatitis B virus carriers in the general
      population in association with a decrease in the incidence of hepatocellular
      carcinoma, one of the most serious complications of chronic hepatitis B virus
      infection. Side effects have been reported including the risk of central nervous
      system demyelination. However studies have shown no evidence of a significant
      correlation between vaccination and this type of disease. Occurrence of hepatitis
      B in properly vaccinated subjects could result from selection of mutant viral
      strains able to escape detection by the immune system. The recently revised
      benefit-to-risk ratio remains highly favorable for vaccination. Current data
      indicates that the policy of mass vaccination of the population should be
      pursued.

PMID- 10901856
TI  - [Hepatitis C in tropical areas].
AB  - The tropical features of hepatitis C have not yet been fully elucidated due to
      the scarcity of data. However it has been estimated that two-thirds of the
      infected population lives in tropics. The most heavily affected regions are
      Africa, China, and southeast Asia with prevalence rates of 5.3, 3.0, and 2.4 p.
      100 respectively. In several countries mostly in Africa, prevalence rates range
      from 5 to 10 p. 100 or higher. Age is a major risk factor for infection. The
      classic transmission modes, i.e., blood transfusion and intravenous drug use, do
      not account for these high prevalence rates. Another mechanism could be
      parenteral injection under unsafe conditions. The most widespread genotypes in
      tropical areas are genotypes 1, 2, and 3. Other genotypes can be encountered
      locally including genotype 4 in black Africa and Egypt, genotype 6 in southeast
      Asia, and genotypes 1 and 3 in India. The association of hepatitis C with chronic
      liver disease has been the focus of several studies, mainly in Africa. The
      seroprevalence of virus C ranges from 2 to 55 p. 100 in cases of chronic
      hepatitis or cirrhosis and from 0 to 47 p. 100 in cases of hepatocellular cancer.
      Hepatitis C could be the underlying cause of 33 to 50 p. 100 of chronic liver
      diseases not linked to virus B. It is observed more often in patients with
      chronic hepatitis or cirrhosis than cancer in which virus B is dominant.
      Infection by both virus is rare without liver disease but is more frequent in
      patients with cancer than chronic non-tumoral liver disease.

PMID- 10901857
TI  - [Baculovirus: an example of an insect virus of use to humans].
AB  - Baculovirus is a viral pathogen of insects in general and lepidoptera in
      particular. The genome of this large virus consists of a circular, infectious
      bicatenary DNA molecule. At the end of its replication cycle in insects,
      baculovirus produces a large quantity of at least two proteins, i.e., polyedrine
      and polypeptide P10. These proteins are essential for transmission of the virus
      in nature, but are not necessary in cell cultures. Using molecular recombinant
      techniques, one or both of the genes coding for these proteins can be replaced by
      heterologous genes. In this way, baculovirus raised in vitro can be used to
      produce large quantities of the alien proteins at the end of the multiplication
      cycle. So far more than 3,000 different proteins have been expressed including
      several presenting interest as diagnostic tools (Puumala virus, Herpes simplex
      virus) or therapeutic treatment in man and animals (vaccinations against dengue,
      flu, malaria and production of anti-Rhesus immunoglobulins). Since it is based on
      the use of lepidoptera virus, this system would appear to be particularly safe.
      No vertebrate virus is able to replicate in the cell system used. Use of this
      genetic engineering tool will undoubtedly expand and holds great promise for the
      future.

PMID- 10901858
TI  - [Antiviral vaccines].
AB  - Vaccination has been successful in controlling numerous diseases in man and
      animals. Smallpox has been eradicated and poliomyelitis is on the verge of being
      eradicated. The traditional immunization arsenal includes vaccines using live,
      attenuated, and inactivated organisms. DNA recombinant technology has added two
      new types of vaccines, i.e. subunit vaccines based on purified antigens produced
      by genetic engineering in bacterial, yeast, or animal-cell cultures and live
      recombinant vaccines based on attenuated bacterial or viral vectors. Currently
      the best known examples of these new vaccines are those using poxvirus vectors
      (vaccinia virus, canarypox virus, or fowlpox virus) but new vectors are under
      development. Another application for genetic engineering in the field of
      vaccinology is the development of DNA vaccines using naked plasmid DNA. This
      technique has achieved remarkable results in small rodents but its efficacy,
      safety, and feasibility in man has yet to be demonstrated. Numerous studies are
      now under way to improve the process. In the field of synthetic vaccines,
      lipopeptides have shown promise for induction of cell immune response.
      Development of vaccines for administration by the oral or nasal route may one day
      revolutionize vaccination techniques. However, effective vaccines against
      hepatitis C and HIV have stalled in the face of the complexity and
      pathophysiology of these diseases. These are the greatest challenges confronting
      scientists at the dawn of the new millennium.

PMID- 10901859
TI  - [Tropical virology and the collaborative system].

PMID- 10901860
TI  - Liverpool Oncology Service: new kid on the block.

PMID- 10901861
TI  - Primary intrathoracic malignant fibrous histiocytoma and angiosarcoma.
AB  - Primary intrathoracic malignant fibrous histiocytoma and angiosarcoma are rare
      sarcomas constituting less than 0.2% of lung cancers. The typical imaging
      appearance is a large, well-circumscribed, non-cavitating, non-calcified,
      peripheral lung mass without hilar or mediastinal lymphadenopathy. Bronchoscopy
      and percutaneous needle aspiration are of limited value in differential
      diagnosis, and thoracotomy is warranted for definitive diagnosis.

PMID- 10901862
TI  - Chest radiographic findings following video-assisted thoracoscopic lung volume
      reduction surgery for emphysema.
AB  - Surgical reduction of lung volume is being investigated as a promising
      alternative in the treatment of selected patients with severe debilitating
      emphysema. Following bilateral video-assisted thoracoscopic surgical resection
      (VATS) of emphysematous lung tissue, patients show improvements in exercise
      tolerance, dyspnoea, increases in oxygenation, decreased airway obstruction and
      enhanced quality of life. The postoperative findings in the first 24 patients who
      underwent bilateral VATS volume reduction are described. Pneumothoraces developed
      in all patients, often with unusual shapes related to the surgical sutures.
      Perihilar, pulmonary and paramediastinal pulmonary parenchymal opacities were
      seen in approximately half of the patients, representing areas of pulmonary
      contusion, atelectasis and/or haemorrhage associated with the staple lines. The
      purpose of the present study is to describe the immediate postoperative chest
      radiographic appearances and to familiarize radiologists with the surgical
      procedure.

PMID- 10901863
TI  - Epidermal cyst of the breast: detection in a screening programme.
AB  - Two cases of epidermal cyst of the breast, a rare benign condition, were detected
      during a 3-year period in a mammographic screening programme, from 57,954
      screening examinations. It is not uncommon for epidermal cysts to be initially
      misdiagnosed. The mammographic, ultrasound and histological features are
      presented. It is recommended that these lesions be resected because they possibly
      have malignant potential.

PMID- 10901864
TI  - Diffusion-weighted magnetic resonance imaging of intracranial epidermoid tumours.
AB  - Intracranial epidermoids can closely mimic cerebrospinal fluid (CSF) on MRI and
      CT. Therefore epidermoids can be difficult to detect, or distinguish from CSF.
      Three cases of intracranial epidermoid are presented, one of which closely
      mimicked an arachnoid cyst on CT and routine MRI sequences. Diffusion-weighted
      magnetic resonance imaging (DWI) was performed. All three epidermoids
      demonstrated marked restriction of diffusion relative to CSF, clearly defining
      the extent of each lesion, and allowing differentiation from an arachnoid cyst or
      an enlarged CSF space.

PMID- 10901865
TI  - The role of the sonologist in a sonographer-based practice.
AB  - In many foetal medicine units and private practices, sonographers have gained
      considerable responsibility and independence. Still, there is a wide divergence
      of opinion as to their proper role, and to the role of the reporting doctor. The
      present study examines the role of the sonologist in three sonographer-based
      obstetric and gynaecological ultrasound practices. During a 25-day period, 14
      sonographers filled out a questionnaire for each patient they scanned. Questions
      included indication for scan, whether or not and why the patient was scanned
      and/or seen by a sonologist, and abnormalities found. Information regarding 700
      patients was obtained. Forty-eight patients were excluded because they were also
      booked to see a doctor. Of the remaining 652 patients, 74.5% had obstetric
      indications and 25.5% had gynaecological indications. Ten per cent of all
      patients scheduled to be scanned only by a sonographer also needed to be scanned
      by a sonologist, and 34.5% of all patients had contact with a doctor
      unexpectedly, most commonly to explain findings or arrange treatment and tests.
      In conclusion, in a sonographer-based practice the sonologist is often required
      to provide direct patient care beyond simple report writing. Therefore optimal
      patient management would require an on-site sonologist.

PMID- 10901866
TI  - Spinal Schmorl's nodes: sagittal sectional imaging and pathological examination.
AB  - The presence, location and number of Schmorl's nodes was determined in the
      thoracolumbar spines of 70 motor vehicle accident victims using radiographic
      examination of a midline sagittal section and subsequent pathological
      examinations, including histology. In 28% of spines, a greater number of
      Schmorl's nodes were identified with radiography, while in 44%, pathological
      examination revealed a greater number of nodes. The visibility of Schmorl's nodes
      was enhanced by using a sagittal radiographic approach, and, in contrast to
      previous work, nodes below 0.5 cm2 were readily detected. The results of the
      present study offer an additional imaging technique for postmortem analysis of
      the spine, and support the use of sagittal MR imaging for the evaluation of this
      condition.

PMID- 10901867
TI  - Stereoscopic presentation of computed tomography and magnetic resonance images.
AB  - This technical note describes a direct and simple method of stereoscopically
      presenting three-dimensional (3-D) CT and MRI volumetric models. This method has
      negligible cost both in monetary terms and in extra processing time, is extremely
      accessible, easy to learn and apply and can be effectively used in the absence of
      any sophisticated equipment. It has the potential to greatly boost the
      communications value of many complex studies where 3-D models are already
      normally generated.

PMID- 10901868
TI  - The role of computed tomography in the diagnosis of arterial gas embolism in
      fatal diving accidents in Tasmania.
AB  - Four cases of fatal diving accidents in Tasmania are presented, highlighting the
      role of CT in the investigation of diving fatalities. The CT technique allows
      rapid diagnosis when arterial gas embolism (AGE) is suspected. The traditional
      method of investigation, underwater autopsy, is a difficult procedure that
      requires specialized training in which the subtle diagnosis of AGE may be
      completely missed. Facilities for performing underwater autopsies are normally
      available only in tertiary referral centres, and therefore the diagnosis of AGE
      may be missed due to lack of facilities. The use of CT in the diagnosis of AGE in
      divers was first utilized in the early 1980s but has still not become widely
      adopted in forensic practice. This radiological technique has the advantage of
      being sensitive, quick, reliable, readily available and provides a permanent
      record. For hospitals that do not have a resident forensic pathologist, a CT scan
      can be easily performed and interpreted to eliminate the possibility of AGE.
      There are a number of pitfalls in the diagnosis of AGE with CT, particularly
      intravascular gas production following postmortem fermentation and off-gassing.
      Awareness of these pitfalls will help the radiologist in making a correct
      diagnosis of AGE.

PMID- 10901869
TI  - A review of 1019 consecutive cases of polycystic ovary syndrome demonstrated by
      ultrasound.
AB  - Analysis of a cohort of 1019 consecutive subjects with ultrasonically
      demonstrable polycystic ovary (PCO) syndrome demonstrated a significant
      relationship between biochemical parameters and clinical symptoms such as
      menstrual frequency and severity of hirsutism. One hundred and forty-four
      subjects presented with involuntary infertility and only eight cases had
      unexplained infertility apart from PCO.

PMID- 10901870
TI  - Corrosion of lead shielding in a radiology department.
AB  - Corrosion of lead sheet used for structural radiation protection in the Princess
      Alexandra Hospital radiology department has been identified. The corrosion is
      thought to have been caused by organic acid vapours released from oregon timber
      wall panelling. Non-destructive testing (NDT) and X-ray transmission measurements
      were used to define the extent and severity of damage, and subsequently to
      provide the data necessary for estimation of staff and public radiation doses.
      Although radiation dose limits have not been exceeded, corrective actions
      including structural modifications and staff information sessions have been
      undertaken.

PMID- 10901871
TI  - Survey of mammographic cassette light output.
AB  - The purpose of the present paper was to assess the variation in light output from
      clinical mammographic screens, particularly in relationship to age and
      radiographic usage. The light output from 156 mammographic cassettes from 17
      clinical centres was measured on site using a novel light detector. Survey
      information on cassette age and usage was collected. Where possible, screen
      manufacture date was supplied by the vendor. One cassette from each centre was
      measured at a standard laboratory to allow normalization of all measurements.
      Three centres were found to have cassettes in clinical use whose light outputs
      varied by an amount incompatible with current Royal Australasian College of
      Radiologists (RACR) standards. These centres used cassettes whose ages varied
      widely. No correlation between light output and radiographic usage was found.
      Older cassettes were found to have a slight increase in light output. A small
      reduction of light output was measured between screen regions of high and low
      radiation exposure histories. Replacement of mammographic screens should not be
      based on an expectation of light output reduction due to age or usage. Rather,
      all mammographic screens should be replaced simultaneously as indicated by
      factors such as failure of screen-film contact or the presence of screen-related
      image artefacts.

PMID- 10901872
TI  - Primary malignant mediastinal germ cell tumours: a literature review and a study
      of 18 cases.
AB  - From 1957 to 1992, 18 cases of primary mediastinal germ cell tumours were
      referred to the Peter MacCallum Cancer Institute (PMCI). Six were seminomas, six
      were mixed germ cell tumours, two were embryonal cell carcinomas, three were
      teratocarcinomas and one was labelled an 'anaplastic germ cell tumour'. Two of
      the 18 patients were female. For seminomas, surgical (and in one case
      chemotherapeutic) debulking, followed by radiotherapy produced the best results.
      Mediastinal doses ranged from 30 to 40 Gy. Local control was achieved in those
      patients receiving mediastinal radiotherapy. Four patients currently survive
      disease-free. The non-seminomatous germ cell tumours showed a significantly
      poorer survival, and only two of 12 patients remain alive in remission at 110 and
      130 months after diagnosis. Survival has been updated as of November 1997.
      Attention is focused on the anterior position of the primary germ cell tumours in
      the mediastinum. A review of the literature up to and including 1997 is
      presented.

PMID- 10901873
TI  - Carcinoma of the male breast: a review of adjuvant therapy.
AB  - The purpose of the present paper was to evaluate the characteristics and outcomes
      of male breast cancer patients seen for adjuvant therapy at a single institution.
      A retrospective review of computerized records in the Departments of Medical and
      Radiation Oncology at the Royal Prince Alfred Hospital (RPAH) was undertaken.
      Between 1983 and 1996, 24 men were referred for treatment of breast cancer. Of
      these, 19 had localized breast cancer, four had metastatic disease and one had
      ductal carcinoma in situ (DCIS). The median age was 57.5 years (range: 26-78) and
      median follow-up was 6.2 years (range: 0.6-36). Pathological staging was
      performed. Survival was assessed using actuarial life table analysis. Of the 19
      patients who presented with localized disease, there were 12 T1, five T2 and two
      T4 cancers. Eleven patients had axillary lymph node involvement. Ten patients
      were oestrogen receptor (ER) positive, two patients were ER negative and seven
      patients had unknown receptor status. All patients underwent surgery. Eleven
      patients received radiotherapy. The median dose and dose per fraction were 50 Gy
      and 2 Gy, respectively. Adjuvant systemic therapy was delivered to 10 patients,
      of whom nine were node-positive. Four patients received chemotherapy alone, three
      patients received chemotherapy and tamoxifen, and three patients received
      tamoxifen only. Seven patients relapsed (one local, five distant, one both). Of
      the two patients with local relapses, one had received radiotherapy. Of the
      distant failures, four of six patients had no systemic therapy. There were only
      two node-positive patients who were not given systemic treatment and both
      relapsed. Median survival in all patients with invasive cancer was 7.5 years, and
      in those with localized disease it was 7.6 years. The median survival of node
      positive patients was 3.8 years. In node-negative patients the median survival
      had not been reached at a median follow-up of 6.2 years. The majority of patients
      (12/14) with known receptor status were ER+, a finding that parallels those of
      other studies. Local control rates were 88% (7/8) in patients who had mastectomy
      alone and 91% (10/11) in those patients receiving adjuvant radiotherapy. Systemic
      therapy was found to be beneficial in patients with node-positive disease.
      Chemotherapy was administered more frequently than hormonal therapy. The median
      survivals were consistent with those reported in other series.

PMID- 10901874
TI  - Covering the CSF space: does teaching make a difference?
AB  - Following a paediatric teaching course for radiation oncology registrars which
      specifically addressed the method for planning cranial irradiation, a lateral
      skull simulation film was sent to all attendees to assess the effect of the
      teaching. To assess current clinical practice in New Zealand, a copy of the same
      radiograph was sent to radiation oncologists who had not attended the course.
      Recommendations from the course were that 10-mm margins should be placed in the
      regions of the cribiform plate and the floor of the middle cranial fossa.
      However, only 6.9% of the attendees marked the film with the recommended 10-mm
      margins. Dose profiles are also presented to support the use of 10-mm margins.

PMID- 10901875
TI  - Tongue cancer in younger patients.
AB  - Tongue cancer involving the anterior tongue often presents at an early stage. The
      aetiology is strongly associated with smoking and alcohol abuse similar to other
      squamous cell carcinomas (SCC) of the head and neck (HN). Surgery and
      radiotherapy, either alone or together, offer the prospect of cure in the
      majority of patients. However, there remains a group of younger patients less
      than 40 years old for whom outcome is often poor. Presented here is the case of a
      24-year-old woman who developed SCC of the anterior tongue. Despite treatment,
      loco-regional relapse occurred resulting in death. The literature identifies a
      distinct subgroup of younger patients who develop HN SCC, particularly of the
      oral cavity. The aetiology remains unclear. Recent studies have looked at the
      prognostic significance of various new non-clinico-pathological markers in HN SCC
      (including p53 tumour suppressor gene, cyclin D1 protein, Ki 67 antigen and
      tumour angiogenesis). The majority of these studies, as expected, have involved
      the typical HN patient (male, aged > 60 years old). However, the relevance of
      these studies is of likely importance to all patients diagnosed with HN SCC. The
      recent use of these non-clinical-pathological markers in HN SCC, including
      reference to such studies in younger patients, is discussed. The English
      literature during the past 30 years is reviewed with reference to the diagnosis
      of tongue SCC in younger patients.

PMID- 10901876
TI  - Clinical audit of a new radiation oncology department in the first 20 months of
      establishment.
AB  - This audit was carried out to examine the workload statistics of the Radiation
      Oncology Department at Liverpool Hospital in its first 20 months of operation,
      and their implications for the delivery of radiation oncology services in the
      Southwestern Sydney Area Health Service (SWSAHS). Data on patient demographics,
      primary diagnosis and radiotherapy treatment details from April 1995 to December
      1996 were analysed. In this time period, 1329 new patients were seen; 90.6% of
      them lived in the local area health service and approximately 30% came from a non
      English-speaking background. The most common primary tumour sites were breast
      (25%), prostate (17%) and lung (15%). Nine hundred and ninety-eight of the new
      patients (74%) proceeded to have radiotherapy. Fifty-seven per cent were treated
      radically with curative or adjuvant intent, the remainder were treated
      palliatively for symptom control or local control. The most commonly used
      fractionation schedules were 31-35 fractions for radical treatment and 1-5
      fractions for palliative treatment. Forty patients (4%) did not complete the
      treatment course as planned. Eighty-nine patients (9%) were retreated in the same
      time period. These workload statistics were helpful in determining ongoing
      workload and planning future expansion.

PMID- 10901877
TI  - Gastric irradiation for MALT lymphoma: reducing the target volume, fast!
AB  - A case of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma
      treated with radiotherapy alone is reported here. This case highlights treatment
      issues related to the variability in size and position of the stomach, and the
      substantial reduction in the size of the irradiated volume achieved by treating
      the patient in a fasting state.

PMID- 10901878
TI  - Creutzfeldt-Jakob disease: magnetic resonance imaging findings.
AB  - Rapidly progressive dementia in an adult with findings of bilateral, symmetric
      high signal intensity on T2-weighted sequences and normal findings on T1-weighted
      sequences predominantly in the deep grey matter is suggestive of Creutzfeldt
      Jakob disease (CJD). The peripheral cortex may be involved, as it was in the
      present case. The absence of subcortical periventricular white matter high signal
      intensity suggests that symmetric high signal intensities within the basal
      ganglia and cortical grey matter are more likely to be due to a degenerative
      process rather than due to ischaemia, infection or tumour.

PMID- 10901879
TI  - Transvaginal ultrasound diagnosis of a live twin tubal ectopic pregnancy.
AB  - A case of live twin tubal ectopic pregnancy diagnosed by transvaginal ultrasound
      is presented. This is a rare occurrence and we have calculated the incidence to
      be approximately 1:125,000 pregnancies. There have been more than 100 case
      reports of twin tubal ectopic pregnancy but only four previous reports where two
      foetal heart motions have been visualized. The introduction of high-resolution
      transvaginal ultrasound has resulted in earlier diagnosis of ectopic pregnancy
      and contributed to the decrease in morbidity that has occurred over recent years.

PMID- 10901880
TI  - Hepatic plasmacytomas: case report and review of imaging features.
AB  - Extramedullary plasmacytomas are uncommon and have a better prognosis than
      disseminated myeloma. We describe the second case of hepatic plasmacytomas
      (multiple) following a solitary bone plasmacytoma. The imaging characteristics of
      the few reported cases of these rare hepatic tumours are compared. The value of
      ultrasound in the assessment of liver lesions is emphasized.

PMID- 10901881
TI  - Pelvi-calyceal cast formation following silver nitrate treatment for chyluria.
AB  - A case of chyluria is reported in which anuria followed instillation of 3% silver
      nitrate into the collecting system of both kidneys, with unusual radiographic
      features. Plain radiographic, ultrasound and computed tomographic findings are
      discussed. To the best of the authors' knowledge this has not been previously
      described in the literature.

PMID- 10901882
TI  - 'Stalkitis' in a pregnant 32-year-old woman: a rare cause of diabetes insipidus.
AB  - A case of lymphocytic infundibulo-neurohypophysitis (LINH) or 'stalkitis' in a 32
      year-old woman who presented with diabetes insipidus (DI) during pregnancy is
      reported here. The diagnosis was made with MR imaging. The clinical and
      radiological features of this rare disorder and the differential diagnosis of
      infundibular mass lesions are discussed. The differentiation from lymphocytic
      adenohypophysitis (LAH) is made. No improvement of the DI accompanying LINH is
      achieved with trans-sphenoidal surgery. Hence, recognition of typical cases with
      MR imaging and appropriate medical management avoids unnecessary neurosurgery.
      This is the second reported case of LINH associated with pregnancy and may
      suggest an association.

PMID- 10901883
TI  - Breast metastasis in osteosarcoma.
AB  - A young girl with a history of chondroblastic osteosarcoma of the tibia developed
      a pulmonary metastasis which was treated by metastasectomy, chemotherapy and lung
      irradiation. There years later, at the age of 15, she developed a breast mass
      which was excised and which proved to be a poorly differentiated sarcoma. This
      was almost certainly a metastasis rather than a radiation-induced second primary
      tumour, in view of the short interval since radiotherapy. The ultrasonographic
      features of this lesion are presented here and the differential diagnosis is
      discussed in this context.

PMID- 10901884
TI  - Extradural cavernous haemangioma simulating a disc protrusion.
AB  - Cavernous haemangiomas confined to the epidural space are rare and are therefore
      infrequently considered in the differential diagnosis of spinal epidural masses.
      In order to draw attention to this diagnosis, a case in which an epidural
      cavernous haemangioma simulates a lateral/foraminal disc protrusion is presented.

PMID- 10901885
TI  - Giant cell tumour of the temporal bone: case report and review of the literature.
AB  - This paper presents an expansile lesion of the temporal bone, in a 14-year-old
      boy, that was initially diagnosed as intra-osseous meningioma from CT appearance.
      At histopathology a final diagnosis of giant cell tumour was made. A brief review
      of the literature is presented for this rare case.

PMID- 10901886
TI  - Popliteal artery pseudo-aneurysm following penetrating trauma.
AB  - Popliteal artery pseudo-aneurysm due to accidental penetrating trauma, once
      common during world wars, is now rare. It may require amputation due to ischaemic
      complication. One such case is detailed here. The angiographic findings,
      complications, management and literature review are provided.

PMID- 10901887
TI  - Perfusion of the oesophagus and stomach during hepatic artery chemotherapy via an
      aberrant gastric artery.
AB  - Symptoms of pain, dyspepsia and nausea arising during the administration of
      intrahepatic chemotherapy should be investigated with endoscopy to exclude
      inadvertent perfusion of the stomach.

PMID- 10901888
TI  - Residual pituitary enlargement in primary hypothyroidism despite 1 1/2 years of L
      thyroxine therapy.
AB  - Pituitary hyperplasia consequent to untreated primary hypothyroidism undergoes
      impressive regression following thyroxine therapy. We describe a young man with
      primary hypothyroidism and pituitary hyperplasia, who showed significant but
      incomplete regression of pituitary enlargement despite 18 months of L-thyroxine
      therapy (1 year in replacement dose (150 micrograms/day) and an additional 6
      months in suppressive dose (300 micrograms/day)).

PMID- 10901889
TI  - Pre-operative radiotherapy for locally advanced carcinoma of the rectum: future
      management or standard of care.

PMID- 10901890
TI  - Imaging diagnosis of abdominal and pelvic sarcomas.
AB  - Sarcomas of the abdomen and pelvis are rare malignant mesenchymal neoplasms that
      often remain undiagnosed until they attain large size. Complete tumour resection
      is associated with improved patient survival. Detection and delineation of the
      tumour, its extent and its relationship with surrounding tissues are important
      for surgical planning. Radiography, barium studies, and intravenous urography are
      of limited value in the imaging diagnosis of abdominal and pelvic sarcomas.
      Ultrasound is sensitive for detecting neoplasms larger than 6 cm. Computed
      tomography is useful for detection, defining extent, and predicting resectability
      of the primary tumour, evaluation of response to treatment, and detecting
      recurrence and metastasis. Sarcomas are predominantly large, poorly demarcated,
      heterogeneous masses of muscle density with haemorrhage or necrosis.

PMID- 10901891
TI  - Role of the medical physicist in interventional radiology.
AB  - Interventional radiological procedures have significantly increased the
      probability for the expression of deterministic detriment to the patient. It is
      the responsibility of the consulting medical physicist to undertake the
      responsibility that (i) appropriate equipment is specified and purchased; (ii)
      the equipment purchased produces the best possible image quality for the minimum
      dose; (iii) accurate dosimetry is measured, calculated and recorded; (iv)
      interventional physicians and surgeons are adequately trained in the fundamental
      techniques that will minimize the dose to both patients and staff, while
      maintaining high image quality; and (v) interventional protocols, record keeping
      and patient follow-up, in the case of deterministic doses, are appropriately
      implemented.

PMID- 10901892
TI  - High-resolution ultrasound to diagnose melanoma metastases in patients with
      clinically palpable lymph nodes.
AB  - High-resolution ultrasound was used to determine if it could predict the presence
      of metastatic disease in 52 patients with melanoma who had developed newly
      palpable lymph nodes during clinical follow-up. Ultrasound proved accurate in
      diagnosing the presence of nodal metastases; it had a sensitivity of 94%, a
      specificity of 87% and an accuracy of 89%. The ultrasound features which together
      were diagnostic of the presence of nodal metastases were a node thickness greater
      than two-thirds of the node length and the presence of low-level echoes in the
      node. When these two features were both present on ultrasound, node metastases
      were present in every case. Ultrasound can be used to evaluate newly palpable
      lymph nodes in patients with melanoma. A normal ultrasound finding does not
      exclude micrometastases, but a lymph node showing the two key ultrasound features
      aforementioned is highly likely to contain metastatic disease and should be
      treated accordingly.

PMID- 10901893
TI  - Comparison of two Doppler ultrasound criteria for grading cervical internal
      carotid artery stenosis.
AB  - In a review of 49 carotid arteries that had been assessed by ultrasound and
      angiography, two Doppler criteria were compared for accuracy in grading internal
      carotid artery (ICA) stenosis. The Seattle criteria for Doppler spectral analysis
      and the internal-to-common carotid artery peak systolic velocity ratio were of
      similar accuracy. When used in combination, there was an increase in sensitivity
      compared with the use of a single criterion. The velocity ratio had a higher
      sensitivity for detection of high-grade stenosis, but it tended to overestimate
      the grade of stenosis more than the Seattle criteria. To increase the sensitivity
      for detection of severe stenosis, the criteria should be used together and the
      higher grade of stenosis should be taken if there is a mismatch in assessment.

PMID- 10901894
TI  - Ultrasound contrast agent Levovist in colour Doppler sonography of hepatocellular
      carcinoma in Chinese patients.
AB  - In a phase IIIb clinical trial of the ultrasound contrast agent Levovist
      (Schering AG, Berlin, Germany), the role of Levovist in the management of
      patients with clinically suspected hepatocellular carcinoma (HCC) was evaluated
      and its efficacy was assessed. The assessment included the duration of
      diagnostically usable Doppler signal enhancement, and safety and tolerance of
      intravenous administration. All patients with clinically suspected hepatocellular
      carcinoma were referred for Doppler sonographic examination over a 5-month period
      and lesions with absent or suboptimal Doppler signals were included in the trial.
      A total of 300 mg/mL in concentration (8.5 mL) of Levovist was administered
      through a peripheral vein while Doppler signal intensity in the lesion, based on
      a visual score, was recorded. Blood pressure and pulse were recorded before and
      after injection. Thirty-eight patients were examined, of which 29 were included
      in the trial. The lesions were subsequently proven histologically to be 19 HCC,
      one cholangiocarcinoma, two regeneration nodules and one colonic metastasis. For
      six patients in whom histological proof was not available, the diagnosis of HCC
      was suggested based on markedly elevated serum alpha-fetoprotein levels. All but
      one (96%) of the 25 HCC demonstrated increased Doppler signal after Levovist.
      There were no Doppler signals before and after Levovist injection in three non
      HCC lesions (two regeneration nodules and one colonic metastasis). Two patients
      (6.9%) suffered minor adverse reactions of nausea and vomiting. The results show
      that Levovist is safe and is able to improve lesion characterization and increase
      diagnostic confidence of hepatocellular carcinoma by enhancing tumour
      vascularization Doppler signal intensity.

PMID- 10901895
TI  - Transfemoral venous liver biopsy: common problems and complications.
AB  - Liver biopsy is still most commonly done via the percutaneous route; however,
      increasingly, transvascular venous liver biopsy has been used in patients with
      bleeding disorders. Although the jugular route is now generally favoured, a
      transfemoral route can be a useful alternative technique when the jugular route
      is not available. We describe the transfemoral technique and outline a number of
      commonly encountered problems and complications and suggested methods of
      addressing them.

PMID- 10901896
TI  - Chemo-embolization of hepatic tumours.
AB  - Over the past decade, increasing use of chemo-embolization with chemotherapeutic
      agents emulsified in oil has been made in the treatment of both primary and
      metastatic liver tumours. These lesions are often not amenable to surgical
      resection and are not responsive to systemic chemotherapy. Chemo-embolization
      provides an additional therapeutic option which, in some instances, can provide
      significant benefit. This pictorial review discusses the technique of chemo
      embolization, as well as aspects of patient selection, complications, and tumour
      response.

PMID- 10901897
TI  - Ultrasonographic diagnosis in abdominal tuberculosis.
AB  - Sonographic findings were retrospectively analysed in 39 patients with proven
      abdominal tuberculosis (TB). The patients were treated over 15 years at a major
      teaching hospital, Mubarak Al-Kabber Hospital, in Kuwait. The findings included
      clear or complex ascites with fine strands, loculations and debris. The other
      findings were lymphadenopathy, bowel wall thickening, omental mass, focal lesions
      in the liver and spleen and psoas abscess. The sonographic findings in abdominal
      TB are not specific but may give valuable information to prevent unnecessary
      laparotomy.

PMID- 10901898
TI  - Acute renal failure in critically ill patients: evaluation of an ultrasound
      contrast agent.
AB  - The purpose of the present paper was to evaluate an ultrasound contrast agent
      (Levovist) in patients with oliguric acute renal failure (ARF) in order to assess
      renal vascularity, differentiate acute tubular from cortical necrosis and predict
      prognosis. Ten intensive care unit (ICU) patients with oliguric ARF were
      prospectively investigated by ultrasound including colour, power and pulsed
      Doppler before and after injection of Levovist. Doppler signals were graded as
      absent, equivocal or present from the inner and outer portions of the renal
      parenchyma, and these findings were correlated with clinical parameters and
      outcome. Only one patient had findings in keeping with acute cortical necrosis.
      All patients who survived had parenchymal vascularity while only three of six
      (50%) who died had parenchymal vascularity after Levovist. The ultrasound
      contrast caused no side effects and additional information was provided which
      improved diagnostic confidence, enabled appropriate classification of patients as
      having tubular or cortical necrosis and therefore added prognostic information.

PMID- 10901899
TI  - Treatment of infrarenal aortic stenosis by stent placement: a 6-year experience.
AB  - There is a significant re-stenosis rate with percutaneous treatment of stenoses
      of the infrarenal abdominal aorta with balloon angioplasty. Since 1990 the
      authors have primarily treated local infrarenal aortic stenoses with metallic
      endoluminal stents. The authors' experience with 12 consecutive patients (nine
      women and three men, aged from 30 to 72 years (mean age = 57 years)) is
      presented. Follow-up is available in 11 cases over 7-78 months (mean 32 months).
      The procedure was technically successful in all patients. Of the 11 patients with
      follow-up available, claudication was cured (n = 7) or significantly improved (n
      = 4). Those with persisting claudication had concurrent distal arterial disease.
      Periprocedural complications occurred in five cases, with two significant
      complications. One case required iliac angioplasty for embolized aortic
      atherosclerotic plaque, and one case required surgical thrombectomy and vein
      patch for iliac thrombosis complicating iliac dissection, without long-term
      sequelae in either case. One patient has had recurrent symptomatic aortic
      stenosis occurring 6 years after initial stenting, which responded to further
      stent insertion. Primary patency of 91% and secondary assisted patency of 100%
      has been achieved. Primary treatment of infrarenal aortic stenosis with
      endoluminal stenting results in high patency rates, with low morbidity and
      relatively low complication rates.

PMID- 10901900
TI  - Non-traumatic spinal extradural haematoma: magnetic resonance findings.
AB  - Non-traumatic extradural spinal haematoma is an uncommon condition that is
      usually associated with a poor outcome. It may present acutely with signs and
      symptoms of major neurological dysfunction secondary to cord compression, or
      subacutely over a number of days or weeks with fluctuating symptoms. The exact
      aetiology of this condition is incompletely understood, but it is believed that
      the blood is venous in origin, as distinct from the arterial origin of
      intracranial extradural haematomas. Causes of non-traumatic extradural spinal
      haematoma include anticoagulation, vasculitis such as systemic lupus
      erythematosus (SLE), and spinal arteriovenous malformations. Conditions that may
      mimic an acute spinal haematoma include extradural abscess and extradural
      metastatic infiltration. It is important to make a diagnosis of extradural
      compression because surgery may offer the best hope in restoring neurological
      function in these patients. Imaging modalities used for the investigation of
      extradural haematomas include myelography, CT myelography (CTM) and MRI with or
      without gadolinium enhancement. The MR appearances of acute extradural abscess
      and extradural tumour can mimic an extradural haematoma. In subacute haematoma,
      owing to the magnetic properties of blood degradation products, MR is more
      specific in diagnosing and ageing of the haematoma.

PMID- 10901901
TI  - A comparative study of a digital radiography system.
AB  - The present study aimed to examine the efficiency of a new digital radiography
      system that was installed in the Royal Adelaide Hospital in September 1997, as
      compared to the existing conventional radiography system. A total of 55
      examinations were observed over a 3-week period in January, and these consisted
      of 18 digital and 10 conventional chest examinations, and 27 conventional
      orthopaedic examinations. These were combined with 18 digital orthopaedic
      examinations recorded from a prior study. Total examination time was broken into
      several components, of which reporting time was of the most interest. The mean
      reporting times for digital and conventional chest examinations were 17 and 25
      min, respectively, a significant (P < 0.1) 8-min difference. The orthopaedic
      examinations revealed mean reporting times of 8 and 26 min for digital and
      conventional systems, respectively; a significant (P < 0.001) 18-min difference.
      These results demonstrate that the digital system is a faster, more efficient
      system for the reporting of X-rays.

PMID- 10901902
TI  - A time-motion study of digital radiography at implementation.
AB  - With increasing budgetary restraints on the health system, it is apparent that
      the main contribution that radiology departments can make to significant cost
      reduction in hospitals is to decrease the length of time between requesting an X
      ray examination and receiving the report (and images). Digital radiography (DR)
      was introduced into the Radiology Department at the Royal Adelaide Hospital as a
      pilot project to research the cost-benefits and efficiency of the system, and to
      determine future directions for planning a digital department. The business plan
      developed prior to implementation of this pilot project predicted a saving of one
      bed-day per inpatient when a fully digital department with a picture archiving
      and communication system (PACS) is installed. This initial study comparing DR and
      conventional radiography (convR) provides baseline data and shows encouraging
      results for more rapid transmission of reports to clinicians.

PMID- 10901903
TI  - Contrast-enhanced Doppler ultrasound for renal artery stenosis.
AB  - The use of renal artery Doppler ultrasound for the diagnosis of renal artery
      stenosis is a well-established technique in selected populations, but the
      technical failure rate of the examination leading to incomplete studies is a
      major drawback. The results of ultrasound contrast-enhanced renal artery Doppler
      for renal artery stenosis, using the echo-enhancing agent, Levovist, are reported
      here. Sixteen patients (22 arteries) were examined with Levovist. The technical
      success rate of these examinations was 91%, and all four renal artery stenoses
      were correctly identified. It is concluded that the use of ultrasound contrast
      (Levovist) increases the technical success rate of renal artery Doppler
      ultrasound in this setting, with similar accuracy to unenhanced Doppler
      examinations.

PMID- 10901904
TI  - Radiotherapy dose compensation for lung patients.
AB  - The purpose of the present paper is to provide a more homogeneous dose
      distribution in the target volume from compensated anterior and posterior fields
      while the healthy lung is spared by de-weighting the lateral fields. A
      compensation computation which used linear iterations to compute the most
      homogeneous dose distribution across the target volume was applied to produce
      optimum compensator designs. The equivalent tissue-air ratio (E-TAR)
      inhomogeneity correction was applied for the computations using a GE target
      series II planning computer. The compensators designed were tested for accuracy
      in a modified water/lung phantom using a scanning diode and an anthropomorphic
      phantom using thermoluminescent dosimeters. A comparison has been made between
      the compensated and uncompensated plans for the first nine patients who we have
      treated with this technique. The dose profiles produced by the computation agreed
      with the prediction of the computed isodose plans to within +/- 2% at the target
      depth. The thermoluminescent dosimeter (TLD)-measured results in the
      anthropomorphic phantom agreed with the planning computer within +/- 3%. A
      comparison of nine compensated plans of radiotherapy patients for large-volume
      targets in the lung region showed a maximum variation in the target to be 19%
      uncompensated versus 10% compensated. By providing compensated treatment fields
      from anterior and posterior treatment portals, a homogeneous dose that conforms
      well to the target volume is provided. As an added bonus, this enables the
      lateral lung fields to be significantly de-weighted and the healthy lung is
      spared considerable dose.

PMID- 10901905
TI  - Pre-operative chemo-radiotherapy in locally advanced rectal cancer: is this the
      way of future management?
AB  - The purpose of the present paper was to update a prospective analysis (H Elsaleh
      et al. unpubl. data, 1997) investigating the effectiveness and toxicity of pre
      operative pelvic radiotherapy with modest dose 5-fluorouracil (5-FU) in locally
      advanced rectal cancer (T3-T4). A total of 31 patients were assessed (28 T3 and
      three T4 tumours). Pre-operative pelvic radiotherapy was delivered in four
      fields, 45 Gy to the International Commission on Radiation Units and Measurements
      (ICRU) point in 25 fractions over 5 weeks. A radiosensitizing dose of 5-FU was
      delivered at 500 mg/m2 on days 1, 2 and 3, and days 22, 23 and 24. Mesorectal
      excision of the rectal tumour either by anterior or abdomino-perineal resection
      was planned at 4-6 weeks from completion of pre-operative treatment. Response to
      therapy was assessed by fresh macroscopic measurement of the surgical specimen.
      Patients had a low toxicity profile; an estimated 50% or greater response was
      seen in 24 out of 31 (two complete responses). There were no surgical
      difficulties achieving resection. No late complications were documented, although
      follow-up was short. In locally advanced rectal cancer, pre-operative chemo
      radiotherapy had a low toxicity profile. Appropriately fractionated pre-operative
      chemo-radiotherapy is a reasonable option in this disease and should be further
      evaluated. The optimal method of delivery of the radiosensitizing agent (5-FU) is
      the subject of further investigation.

PMID- 10901906
TI  - Simultaneous adjuvant radiotherapy and chemotherapy for stage I and II breast
      cancer.
AB  - The purpose of the present paper was to evaluate treatment outcome after
      conservative breast surgery or mastectomy followed by simultaneous adjuvant
      radiotherapy and cyclophosphamide, methotrexate and fluorouracil (CMF) therapy.
      Two hundred and sixty eight (268) patients were treated at two Australian and two
      New Zealand centres between 1981 and July 1995. One hundred and sixty-nine
      patients underwent conservation surgery and 99 had mastectomies. Median follow-up
      was 53 months. Conventionally fractionated radiation was delivered simultaneously
      during the first two cycles of CMF, avoiding radiation on the Fridays that the
      intravenous components of CMF were delivered. In conservatively treated patients,
      5-year actuarial rates of any recurrence, distant recurrence and overall survival
      were 34.5 +/- 5.2%, 25.4 +/- 4.5% and 75.5 +/- 4.8%, respectively. Crude
      incidence of local relapse at 4 years was 6.3% and at regional/distant sites was
      26.3%. Highest grades of granulocyte toxicity (< 0.5 x 10(9)/L), moist
      desquamation, radiation pneumonitis and persistent breast oedema were recorded in
      10.7, 8.5, 8.9 and 17.2%, respectively. In patients treated by mastectomy, 5-year
      actuarial rates of any recurrence, distant recurrence and overall survival were
      59.7 +/- 7.3%, 56.7 +/- 7.4% and 50.1 +/- 7%. The crude incidence of local
      relapse at 4 years was 5.6% and at regional/distant sites it was 45.7%. The issue
      of appropriate timing of adjuvant therapies has become particularly important
      with the increasing acknowledgement of the value of anthracycline-based regimens.
      For women in lower risk categories (e.g. 1-3 nodes positive or node negative),
      CMF may offer a potentially better therapy, particularly where breast-conserving
      surgical techniques have been used. In such cases CMF allows the simultaneous
      delivery of radiotherapy with the result of optimum local control, without
      compromise or regional or systemic relapse rates. Further randomized trials that
      directly address the optimal integration of the two modalities, such as the one
      carried out in Boston, are clearly necessary.

PMID- 10901907
TI  - Quality assurance audit in an Australasian phase III trial of accelerated
      radiotherapy for head and neck cancer (TROG 91.01). Trans-Tasman Radiation
      Oncology Group.
AB  - The Trans-Tasman Radiation Oncology Group (TROG) initiated a randomized trial,
      testing accelerated (twice daily) radiotherapy against conventional radiotherapy
      for stage III and stage IV squamous cell carcinoma of the head and neck in 1991.
      In 1996, the Trial Management Committee arranged for a technical audit of 76
      cases from 11 institutions, conducted by investigators from interstate
      institutions. A 10% unacceptable protocol violation rate was detected, which
      compares favourably with initial Radiation Therapy Oncology Group (RTOG)
      experience in the late 1970s. Infrastructural deficits with poor quality of
      documentation, incomplete retrieval of films and document return have been
      demonstrated in some cases. The Trans-Tasman Radiation Oncology Group is actively
      pursuing procedural and resourcing issues in order to redress this and is
      actively expanding its Quality Assurance (QA) Programme with an intercentre
      dosimetry study. Ultimately, comprehensive clinical and technical QA site visits
      are planned.

PMID- 10901908
TI  - Faculty of Radiation Oncology survey of work practices.
AB  - The aim of the present paper was to determine the current working conditions of
      practising radiation oncologists (RO) in Australasia and their attitudes towards
      their work and work environment. The authors were requested by the Faculty of
      Radiation Oncology to conduct a survey of Fellows' work conditions and attitudes.
      The need for such a survey arose from a workshop of the Faculty held in Sydney in
      1995, to determine future directions of the Faculty. Issues of potential interest
      were identified at the workshop and supplemented by the authors into a survey
      consisting of both directed and open questions. Respondents were free to remain
      anonymous. An address list of RO was supplied by the Royal Australian and New
      Zealand College of Radiologists (RANZCR). Two mailouts were performed to increase
      the response rate. The survey was completed during the second half of 1996 and
      analysed in 1997. The response rate was 79% (63-100% according to state/country).
      The age range was 30-69 years (median: 43 years; mean: 44 years), and 78% of the
      respondents were male. A public centre was identified as the sole or main place
      of work for 84% of respondents. The number of RO per practice varied from one to
      25 (median: 5). The estimated hours worked per week ranged from 20 to 79 (mean:
      52 h; median: 50 h). There were significant differences in allocation of hours
      between public and private (more clinical hours for private (P = 0.008), more
      teaching hours for public (P = 0.007)) but no difference in total hours. The
      responses for clinical work profile were: 'general' 39%, 'largely subspecialty'
      37% and both 2% (23% did not respond). The proportion whose practice was 'largely
      subspecialty' differed between public and private (53% vs 13%, respectively; P =
      0.06), and varied according to the number of RO in the practice (62% for > five
      RO vs 35% for < or = five RO, P = 0.03). The need for subspecialization for the
      treatment of common tumours (breast, gynaecological etc.) was held by 78% of
      respondents and was related to the number of RO in the practice (100% for > five
      RO vs 81% for < or = five RO, P = 0.002). The number of new patients seen per RO
      in 1995 ranged from 0 to 700 (mean: 342; median: 350), with a significant
      difference between the mean numbers seen in public versus private settings (331
      vs 409, respectively; P = 0.008). Administration of cytotoxics was supervised by
      36% of RO across Australasia but was dependent strongly on the state/country of
      practice (P = 0.0002). The current and preferred roles in clinical management
      were scored as means of 7.9 and 8.7, respectively, on a linear scale from 1
      (mainly technical role) to 10 (significant role in overall management). A total
      of 40% of RO were content with their current time allocation; the remainder
      generally wished to reduce clinical time and increase self-education and/or
      clinical research. Most indicated that they wanted some 'protected time'. Most
      were content to be called a 'radiation oncologist' and wished to retain this
      title; the most common alternative was 'clinical oncologist'. Much of the general
      comment related to perceived loss of control of clinical and academic aspects of
      oncology to other specialties. The present survey is the first to define current
      work practices and to explore attitudes to work. It is clear that many RO
      consider clinical workloads to be excessive, to the exclusion of other work
      related activities. There was a strong feeling that significant changes will be
      required if RO are to maintain the role in cancer management for which they are
      trained.

PMID- 10901909
TI  - Congenital lobar emphysema: antenatal diagnosis and follow up.
AB  - The case of an echogenic mass in the right lung that apparently resolved
      spontaneously prior to delivery is reported here. Postnatal investigations
      revealed congenital lobar emphysema. To the knowledge of the authors, this is the
      first reported case of spontaneous, apparently complete resolution of an
      echogenic lung mass on antenatal ultrasound due to lobar emphysema. The routine
      use of ultrasound to screen for foetal anomalies has led to the discovery of a
      number of incidental findings, such as an echogenic foetal lung mass, that pose a
      challenge to diagnosis and management. The importance of appropriate counselling
      and postnatal follow-up are highlighted.

PMID- 10901910
TI  - Complication of a venous wallstent.
AB  - A case is reported here of effort-related thrombosis of the axillary and
      subclavian veins (Paget-Schrotter syndrome) treated primarily with a combination
      of thrombolysis, percutaneous balloon angioplasty (PTA) and stent insertion, but
      without immediate rib resection. The subsequent course was complicated by
      fracture of the stent, managed by first rib resection.

PMID- 10901911
TI  - Lymphangiomyomatosis: radiological and measured lung function deterioration after
      contrast-enhanced computed tomography.
AB  - Pulmonary lymphangiomyomatosis (LAM) is a rare disease of unknown aetiology which
      occurs exclusively in women, usually of reproductive age. The findings on CT and
      high-resolution CT (HRCT) are well described and characteristic, and in a young
      woman they are virtually pathognomonic. A case of symptomatic, radiological and
      measured lung function deterioration following contrast-enhanced CT in a patient
      with LAM are reported here. These observations, to the authors' knowledge, have
      never been reported before. The authors attempt to explain these observations
      based on the known pathology of LAM.

PMID- 10901912
TI  - Granular cell tumour of the oesophagus: endoscopic ultrasound appearances.
AB  - A case of granular cell tumour of the oesophagus in a middle-aged woman is
      reported. The pathological features and appearances on endoscopic ultrasound
      (EUS) are described, and the role of EUS in the characterization of intramural
      oesophageal tumours is discussed.

PMID- 10901913
TI  - Clostridium septicum septicaemia with myonecrosis.
AB  - A case of fatal spontaneous gas gangrene due to Clostridium septicum septicaemia
      associated with an occult rectal malignancy is presented. This condition has a
      rapid progression and a high mortality even with prompt treatment. It is
      important that the radiologist considers this diagnosis in an appropriate
      clinical setting to allow rapid instigation of appropriate therapy.

PMID- 10901914
TI  - Digital subtraction angiography demonstration of bone hypervascularity in Paget's
      disease.
AB  - Bone hypervascularity is a well-known component of Paget's disease, but has not
      been previously reported on digital subtraction angiography. The features shown
      in the present case include sustained bone enhancement and early venous filling.

PMID- 10901915
TI  - Leiomyosarcoma of the rectum: what role does adjuvant therapy play?
AB  - Leiomyosarcoma of the rectum is an exceedingly rare malignancy and for this
      reason the literature fails to provide definitive management guidelines with
      regard to the place of adjuvant therapies. The role of radiotherapy (RT) is often
      downplayed on the basis of articles written at a time when state-of-the art RT
      equipment was unavailable. A case of leiomyosarcoma of the rectum is presented
      and the literature is reviewed. Because the rarity of this tumour type virtually
      precludes a prospective randomized trial of adjuvant therapies, the authors
      recommend (in otherwise fit patients) postoperative pelvic RT because its
      morbidity is minimal. Smaller tumours may benefit to a greater extent than those
      lesions that are large at presentation and thereby run a worse clinical course.

PMID- 10901917
TI  - Southern Cross Radiological Association.

PMID- 10901916
TI  - Spontaneous arterial thrombosis in association with pancreatic carcinoma:
      diagnosis in interventional management.

PMID- 10901918
TI  - Postoperative liver transplantation assessment by magnetic resonance
      cholangiography.

PMID- 10901919
TI  - Magnetic resonance cholangiopancreatography following liver transplantation.
AB  - The magnetic resonance cholangiopancreatography (MRCP) findings following all
      three forms of biliary anastomosis and some of the common biliary complications
      following liver transplantation have been demonstrated. The ability of this
      technique to image the biliary tree non-invasively in this group of
      immunocompromised patients should represent a substantial advantage over other
      forms of direct imaging such as endoscopic retrograde cholangiopancreatography
      and percutaneous transhepatic cholangiopancreatography. This form of imaging is
      particularly useful when a T-tube is not in place and may provide unique
      information not obtainable by traditional methods of direct imaging. In addition,
      MRCP should improve planning of biliary intervention.

PMID- 10901920
TI  - Magnetic resonance cholangiopancreatography.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive imaging
      method for examining the biliary and pancreatic ducts. The technique uses heavily
      T2-weighted imaging, which produces high signal from bile and other static fluids
      by virtue of their long T2 time, while suppressing background signal. Fast
      scanning techniques, particularly half-Fourier fast spin-echo techniques, are
      continuing to improve image resolution and allow scans within short breath-holds,
      reducing the effects of respiratory movement. The MRCP method has reached a level
      of resolution and reliability where it may well largely replace diagnostic
      endoscopic retrograde cholangiopancreatography (ERCP) in the near future. A
      review of MRCP techniques and imaging findings is presented with emphasis on half
      Fourier imaging, with reference to potential clinical indications and
      limitations. Use of MRCP shows a high sensitivity and specificity for detection
      of biliary dilatation, calculi, strictures and anatomical variants. Experience
      with MR imaging of the pancreatic duct is less extensively described in the
      literature, but pancreatic duct dilatation, calculi and anatomy can now be
      reliably detected. However, as experience with MRCP increases, some sources of
      errors and limitations are becoming apparent, with image artefacts, and gas,
      blood or sludge within ducts potentially mimicking stones or strictures.

PMID- 10901921
TI  - Radiology of the orbital apex.
AB  - The orbital apex, formed by the superior orbital fissure and optic canal, is the
      cross-road between the orbit and the intracranial structures. Pathological
      processes may extend intracranially via the superior orbital fissure and vice
      versa. In addition to intrinsic soft tissue lesions, various pathological
      processes may involve the surrounding osseous anatomy. Malignant lesions arising
      from adjacent structures or from haematogeneous metastasis may also infiltrate
      this region.

PMID- 10901923
TI  - Investigation of thyroid dose due to mammography.
AB  - The radiation dose to the skin overlying the thyroid was measured for 91 women
      undergoing routine mammographic screening. Measurement was made over 6 days using
      thermoluminescent dosimeter (TLD) detectors taped appropriately to the neck. An
      average skin dose of 0.39 +/- 0.22 mGy per mammographic examination was measured
      with measurements ranging from background levels to 1.15 mGy. The average dose
      was significantly correlated to the milliampere-seconds for a total procedure.
      The mediolateral-oblique view was found to give a 2.4-fold greater skin dose at
      the thyroid than the craniocaudal view. After considering depth dose data from
      the literature it was conservatively estimated that the dose to the thyroid gland
      might be 10% of the skin dose overlying the thyroid. This corresponds to an
      average thyroid dose during mammography of approximately 0.04 mGy which is
      considered insignificant compared with the average breast dose (4 mGy) and in
      light of the relevant available literature on the risk to the thyroid.

PMID- 10901922
TI  - Computed tomography of retroperitoneal paragangliomas.
AB  - More than 10% of retroperitoneal paragangliomas are malignant. Histopathological
      appearance is unreliable in distinguishing benign from malignant paragangliomas.
      In this study the computed tomography (CT) features of retroperitoneal
      paragangliomas were analysed to determine if benign neoplasms could be
      distinguished from malignancy by their appearance at imaging. We reviewed the
      clinical profiles and CT scans of 27 benign and seven malignant retroperitoneal
      paragangliomas in 32 patients to determine the presence of any characteristic
      appearances of benign and malignant neoplasms. Extra-adrenal paragangliomas were
      more frequently malignant (50%) than adrenal neoplasms (12.5%). Benign lesions
      were generally smaller (average 6.1 cm) than malignant lesions (average 7.9 cm).
      Benign tumours were more likely to be homogeneous (46.2%) and have well-defined
      margins (92.3%) than malignant tumours (25 and 12.5% respectively). Larger
      tumours were more frequently necrotic. Malignant retroperitoneal paragangliomas
      infiltrated adjacent liver, pancreas, bowel, lymph nodes, blood vessels, or
      metastasized to bone and liver. Malignant retroperitoneal paragangliomas are
      frequently extra-adrenal, large and heterogeneous, with ill-defined margin and
      necrosis. CT is useful for delineating the location, extent and nature of these
      tumours. Infiltration of surrounding tissues or organs, metastases, and
      resectability are accurately assessed by CT.

PMID- 10901924
TI  - Can CT pulmonary angiography replace ventilation-perfusion scans as a first line
      investigation for pulmonary emboli?
AB  - A prospective study was performed to determine efficacy of diagnosis of pulmonary
      emboli by computed tomographic pulmonary angiography (CTPA) in patients who
      underwent both CTPA and ventilation-perfusion (V/Q) scanning. The results were
      compared with the Prospective Investigation of Pulmonary Embolism Diagnosis
      (PIOPED) study in which conventional pulmonary angiography had been performed
      instead of CTPA. Forty-two of 161 (26%) patients had a positive CTPA compared
      with a 27% prevalence in the PIOPED population. Fourteen of 16 patients (87.5%)
      with high-probability V/Q scans also had a positive CTPA compared with 87% in
      PIOPED. Twelve of 40 patients (30%) with intermediate probability V/Q scans also
      had a positive CTPA compared with 34.7% in PIOPED, while 12 of 80 patients (15%)
      who had low-probability V/Q scans had positive CTPA compared with 14.5% in
      PIOPED. Four of 25 patients (16%) with normal V/Q scans had positive CTPA
      compared with 0% in PIOPED. While the present study size was relatively small,
      the results compared favourably with PIOPED, suggesting that equivalent
      prevalence of clot was being detected using CTPA. This result, together with the
      cost considerations, has led us to replace V/Q scanning with CTPA for
      investigation of the majority of cases of suspected, acute pulmonary emboli.

PMID- 10901925
TI  - Magnetic resonance features of focal nodular hyperplasia of the liver.
AB  - The magnetic resonance imaging (MRI) features of 11 biopsy-proven lesions of
      focal nodular hyperplasia (FNH) of the liver were reviewed retrospectively. Only
      three lesions showed atypical features. It is believed MRI can reliably
      differentiate FNH from other liver tumours when strict criteria are fulfilled.

PMID- 10901926
TI  - Cerebral asymmetry in a selected Chinese population.
AB  - Previous studies have demonstrated anatomical differences between the two
      cerebral hemispheres and ethnic differences in cerebral asymmetry. This study
      examined asymmetry of Chinese living in Shanghai. Measurements were taken across
      the frontal, mid-cerebral and occipital regions from normal head computed
      tomography (CT) scans of 200 Chinese Shanghai residents (100 male and 100 female,
      aged 6-73 years, average 48.7 years). The results were compared with reported
      data in the literature. The following results were found: (i) In the frontal
      region the right side was larger than the left in 57.5% of cases, equal in 10.5%
      and smaller in 32% of cases; in the mid-cerebral region the right side was larger
      than the left in 65.5% of cases, equal in 12.5% and smaller in 22% of cases; in
      the occipital regions the right side was larger than the left in 34.5% of cases,
      equal in 8.5% and smaller in 57% of cases. The average right-left differences
      between the frontal, mid-cerebral and occipital regions were 0.43 mm, 0.9 mm and
      0.4 mm respectively. No difference in cerebral asymmetry existed between males
      and females. The occipital lobes showed the greatest individual asymmetry. The
      distribution of cerebral asymmetry of Chinese in Shanghai showed similarity to
      North American Whites rather than North American Blacks, but the average right
      left differences were smaller than those of Whites.

PMID- 10901927
TI  - Validation of a malnutrition screening tool for patients receiving radiotherapy.
AB  - Nutrition screening identifies individuals who are malnourished or at risk of
      becoming malnourished and who may benefit from nutrition support. The aim of this
      study was to validate a new malnutrition screening tool (MST) in cancer patients
      undergoing radiotherapy. The MST was compared with the subjective global
      assessment (SGA) of nutritional status. One hundred and six patients attending
      two cancer care centres in Australia were independently rated as well nourished
      or malnourished using SGA and at risk or not at risk of malnutrition using the
      MST. Convergent validity of the MST was established by determining the ability of
      the MST to predict SGA. According to SGA, 89% of the patients were well nourished
      and 11% were moderately malnourished. According to the MST, 28% of patients were
      at risk of malnutrition. The MST had a sensitivity of 100% and a specificity of
      81%. The positive predictive value was 0.4 and the negative predictive value was
      1.0. The MST is easy to use and is a strong predictor of nutritional status. The
      malnutrition screening tool is a simple, quick, valid tool that can be used to
      identify radiation oncology outpatients who are at risk of malnutrition.

PMID- 10901928
TI  - Lung cancer in patients aged 50 years and younger: clinical characteristics,
      treatment details and outcome.
AB  - Younger patients (< or = 50 years of age) develop lung cancer. Many series report
      5-10% of all cases occurring in younger patients. Outcome, inspite of treatment,
      is universally poor. Females and adenocarcinomas are over-represented and the
      aetiology for such an early-age presentation is unclear. The aims of this
      retrospective study were to review the clinical characteristics, treatment
      details and outcome of patients aged 50 years or younger diagnosed with lung
      cancer (small cell and non-small cell). Over a period of 34 months, 497 lung
      cancer patients were treated at the Liverpool Hospital Cancer Therapy Centre.
      Thirty-seven (7.4%) patients aged less than or equal to 50 years were identified.
      The median age at diagnosis was 44 years (range 32-49 years) in 20 females and 17
      males. Adenocarcinoma was the predominant histological subtype (32%). No referred
      patient had stage I/II disease. Almost 90% of patients were smokers. Median
      survival following diagnosis was 12 months (range, 9 days-68 months) with 70%
      having died by the close of study. The clinical characteristics and outcome of
      young patients in our study were comparable to other similar series.

PMID- 10901929
TI  - Variations in breast tangent radiotherapy: a survey of practice in New South
      Wales and the Australian Capital Territory.
AB  - The breast is a complex anatomical structure where achieving a homogeneous dose
      distribution with radiation treatment is difficult. Despite obvious similarities
      in the approach to such treatment (using tangents) there is variation in the
      process of simulation, planning and treatment between radiation oncologists.
      Previous Australasian studies in the treatment of lung cancer, prostate cancer
      and Hodgkin's disease highlighted considerable variation in many areas of
      treatment. As part of a multicentre breast phantom study involving 10 radiation
      oncology departments throughout New South Wales (NSW) and the Australian Capital
      Territory (ACT), a 22-question survey was distributed. The aim of the survey was
      to assess the extent of variation in the approach to the simulation, planning and
      treatment of early breast cancer using tangents. Responses from 10 different
      radiation oncology departments revealed variation in most areas of the survey.
      There is no reason to assume similar variations do not occur Australasia wide.
      Studies involving overseas radiation oncologists also reveal a wide variation in
      treating early breast cancer. The consequences of such variations remain unclear.

PMID- 10901930
TI  - Gamma-knife radiosurgery for trigeminal neuralgia.
AB  - Gamma knife was installed at the PD Hinduja National Hospital and Medical
      Research Centre, Mumbai, India, in January 1997. In the first year of gamma-knife
      radiosurgery to January 1998, we treated 110 patients, of whom six had medically
      refractory trigeminal neuralgia. Seven treatments were administered to this group
      of six patients (one had bilateral neuralgia). This report evaluates the
      effectiveness of radiosurgery treatment in these patients. The median age of the
      patients was 56 years and there were five males and one female. Following Leksell
      stereotactic frame fixation, a magnetic resonance imaging scan was done in all.
      The Leksell gamma plan was used for planning. A radiosurgery dose of 70-80 Gy was
      delivered to the trigeminal root entry zone, 2-4 mm anterior to the junction of
      the pons and trigeminal nerve with a single 4 mm collimator helmet. Complete pain
      relief was achieved in four patients. Two had partial relief. No patient
      developed any radiosurgery related morbidity during the follow-up period of 5-16
      months. Radiosurgery seems to be an effective approach for medically or
      surgically refractory trigeminal neuralgia.

PMID- 10901931
TI  - Variation in the isocentre of a Philips linear accelerator (SL-20) used for
      stereotactic radiosurgery/stereotactic radiotherapy.
AB  - Stereotactic irradiation, either in the form of stereotactic radiosurgery (SRS)
      or stereotactic radiotherapy (SRT) of brain lesions requires high precision and
      submillimetre accuracy in the isocentre, the main determinants being gantry and
      couch rotations. It is thus necessary to evaluate the isocentre variation due to
      gantry and couch rotations in the particular setup for SRS/SRT. This paper
      describes variation in the isocentre of a Philips (now Elekta) SL-20 linear
      accelerator modified for adapting a couch-mounted radiosurgery system. By
      considering the isocentre as defined by a mechanical index as the standard, the
      variations in the isocentre of the linear accelerator were independently measured
      for the gantry and for couch rotations. The variation in the isocentre for gantry
      rotation was found to be between 0.1 mm and 0.9 mm, conforming to the
      submillimetre accuracy required for SRS/SRT. However, the isocentre variation due
      to couch rotation varied considerably, possibly because the couch is of the RAM
      type. The isocentre variation due to couch rotation is rectified by
      microadjusting the couch mount at the time of treatment using a laser target
      localizing frame. It is our conclusion that a modified linear accelerator can be
      used for performing SRS/SRT after careful and separate evaluation of the
      isocentre stability due to gantry and couch rotations.

PMID- 10901932
TI  - Unilateral megalencephaly associated with contralateral neuronal migration
      defect.
AB  - A case of unilateral megalencephaly associated with contralateral cortical
      dysplasia and grey matter heterotopia is reported. The corpus callosum is a
      genetic and the basal ganglia are dysplastic.

PMID- 10901933
TI  - Life-threatening pica: liver abscess from perforating foreign body.
AB  - A case is presented of a patient with a psychiatric illness and pica who
      developed a pyogenic liver abscess due to perforation of the duodenum by a pen.
      This report emphasizes the importance of ultrasound and computed tomography in
      making a rapid diagnosis. The relative superiority of ultrasound was revealed
      because an anaesthetic was not required for scanning, and in addition to the
      liver abscess, the precise location of the perforating foreign body was
      demonstrated.

PMID- 10901934
TI  - Angiomyoma of the knee joint: value of magnetic resonance imaging.
AB  - A case of angiomyoma as an unusual cause of knee pain is presented and the
      usefulness of magnetic resonance imaging in such a situation is discussed.

PMID- 10901935
TI  - Ulnar nerve injuries of the hand producing intrinsic muscle denervation on
      magnetic resonance imaging.
AB  - Muscle and nerve injuries in the hand may be difficult to detect and diagnose
      clinically. Two cases are reported in which magnetic resonance imaging showed
      ulnar nerve injury and intrinsic hand muscle denervation. The clinical,
      anatomical and radiological features of injury to the deep motor branch of the
      ulnar nerve and associated muscle denervation are discussed and illustrated.

PMID- 10901936
TI  - Traumatic dissection of extracranial internal carotid artery and subclavian
      artery.
AB  - A case of a young, adult male presenting with acute post-traumatic dissection
      involving the left internal carotid and subclavian artery is described.

PMID- 10901937
TI  - A severe, late reaction to radiological contrast media mimicking a sepsis
      syndrome.
AB  - An unusual, severe delayed reaction to non-ionic intravenous contrast media was
      observed. A 44-year-old man underwent a computed tomography scan with non-ionic
      contrast media. Four hours later the patient collapsed with hypotension and
      cardiovascular shock. Aggressive management (including inotropic support and
      fluid resuscitation) was instituted in the intensive care unit. Rigorous imaging
      and biochemical and microbiological investigation failed to identify a source of
      this man's circulatory collapse. A rapid recovery ensued and at 3 months follow
      up the patient was suffering no residual effects from this event. To our
      knowledge, this is only the second report of a severe delayed reaction to
      radiological contrast media and the first that manifested as a prolonged
      hypotensive syndrome.

PMID- 10901938
TI  - Traumatic rupture of the thyroid gland.
AB  - A 24-year-old male presented with marked neck swelling following direct neck
      trauma. Imaging diagnosed a rare case of traumatic thyroid rupture.

PMID- 10901939
TI  - Simulated bone metastases: a case study of two patients with breast cancer.
AB  - Two case studies are used to discuss topical issues current in follow-up
      management of patients with early stage breast cancer. These issues include the
      role of screening and diagnostic bone scintigraphy and patient self-advocacy in
      clinical management.

PMID- 10901940
TI  - Lap belt abdominal aortic trauma.
AB  - A case of vehicle accident trauma to the abdominal aorta in a patient wearing a
      lap-type seat belt is presented, together with its diagnosis and management. The
      role of the radiologist is emphasized.

PMID- 10901942
TI  - Magnetic resonance imaging of penile metastases: a report on five cases.
AB  - Five cases of penile metastases are presented. Axial and sagittal T1-weighted and
      T2-weighted scans were performed in all patients. In some, coronal images were
      also obtained. The penile metastases were most often seen as discrete masses in
      the corpora cavernosa or corpus spongiosum. An atypical pattern of diffuse
      infiltration is also illustrated. Limitations of cavernosography, ultrasound (US)
      and computed tomography (CT) are discussed. The magnetic resonance (MR) features
      of penile metastases and possible role MR may have in the management of these
      patients are described.

PMID- 10901941
TI  - Traumatic cervical distraction complicated by delayed reduction due to traumatic
      vertebral artery pseudo-aneurysm.
AB  - A 23-year-old male involved in a high-speed collision acquired, among other
      injuries, a wide fracture distraction at C2/C3. Reduction was delayed by an
      enlarging vertebral artery pseudo-aneurysm at the site of injury which was
      successfully treated by proximal endovascular occlusion with a detachable polymer
      filled balloon. A traumatic arachnoid cyst or pseudomeningocele was also
      demonstrated at the injury site but intervention was not required. The treatment
      and outcome of these three uncommon injuries in the literature is reviewed and
      discussed. Given the severity of the injury, the absence of severe long-term
      neurological disability is notable.

PMID- 10901943
TI  - Large-cell calcifying Sertoli cell tumour of the testis: associated organ
      anomalies.
AB  - A case is reported of unilateral, focal large-cell calcifying Sertoli cell tumour
      (LCCSCT) of the testis associated with complex endocrine disorders and cardiac
      myxomas. It is believed that there are two distinct groups of patients with this
      tumour: those who have complex dysplastic syndromes and bilateral and multifocal
      tumours; and those without any syndromes but who have unilateral and focal
      tumours. The presented case differs in that, although the patient has a
      unilateral focal tumour, unique organ anomalies, such as renal agenesis and
      inferior vena cava duplication, are also present. These anomalies with LCCSCT
      have not been reported before.

PMID- 10901944
TI  - Ultrasound appearance of schistosomiasis of the testis.
AB  - Schistosomiasis of the testis is rare and its ultrasound findings have not
      previously been documented in the English medical literature. This case report
      describes the ultrasound appearances of a case of schistosomiasis of the testis
      in a 33-year-old male who had recently travelled to Egypt. The ultrasound
      findings are those of a solid testicular mass with a heterogeneous echotexture
      identical to that of most testicular malignancies.

PMID- 10901945
TI  - Ovarian carcinoma relapsing as a cerebellopontine angle tumour.
AB  - Involvement of the central nervous system in epithelial ovarian carcinoma is
      rare. A 46-year-old woman with ovarian carcinoma relapsing with brain metastasis
      is described. She received radiotherapy for the metastasis and survived for 18
      months.

PMID- 10901946
TI  - Classical Kaposi's sarcoma involving bone.
AB  - The clinical course of classical endemic Kaposi's sarcoma is indolent and bone
      involvement is rare unless via direct tumour extension. A case is presented in
      which isolated bone involvement occurred in the absence of significant overlying
      skin disease.

PMID- 10901947
TI  - Diagnosis of dorsal interosseous pseudotumours by magnetic resonance imaging.
AB  - Two middle-aged-patients each presenting with a progressively enlarging mass in
      the first dorsal web space of their hands are reported. Magnetic resonance
      imaging (MRI) demonstrated the cause to be a hypertrophic first dorsal
      interosseous muscle, with normal T1, T2 and post-gadopentetate dimeglumine signal
      characteristics. The ability of MRI to diagnose anatomical variants of hand
      muscles is important in the clinical management of patients with these
      pseudotumours.

PMID- 10901948
TI  - Transcolonic retrograde ureteric catheterization assisted by 3-D computed
      tomography.
AB  - A 42-year-old woman had bladder exstrophy at birth, treated by ureterocolic
      anastomosis of her single kidney. She suffered recurrent hyperammonaemia, leading
      to comas, but refused an ileal conduit. During her most recent coma, it was
      decided to divert her urine to test whether this would reduce hyperammonaemia:
      this was accomplished by transcolonic retrograde catheterization of the ureter.
      This was only possible after computed tomography ureterography to show the
      ureterocolic anastomosis.

PMID- 10901949
TI  - Balo's concentric sclerosis: value of magnetic resonance imaging in diagnosis.
AB  - We report two cases of Balo's concentric sclerosis that demonstrate the typical
      magnetic resonance imaging (MRI) findings of concentric rings of demyelination
      involving the superficial and deep white matter and sparing the cortex. In both
      cases biopsy was not performed as MRI findings and multi-mode evoked potential
      studies were consistent with demyelinating illness. The theories regarding the
      pathogenesis of this peculiar appearance are briefly reviewed.

PMID- 10901950
TI  - Case quiz. Renal parenchymal malacoplakia.

PMID- 10901951
TI  - Dilemmas in the 18-week morphology scan: a review.
AB  - The 18-20-week obstetric ultrasound scan is a commonly performed radiological
      investigation. The sonographic abnormalities demonstrated and management
      implications change frequently. A tertiary referral centre such as the Women's
      and Children's Hospital receives many queries from radiologists regarding the
      further management of their patients. The more common problems have been
      addressed by using a systematic approach to fetal anatomy, and emphasis is placed
      on the need for standardized protocols. The object of this review is to provide
      an obstetric morphology scan update.

PMID- 10901952
TI  - Magnetic resonance evaluation of the labral capsular ligamentous complex: a
      pictorial review.
AB  - Magnetic resonance imaging of the shoulder is a common imaging test, and in the
      course of routine evaluation it can provide accurate information regarding the
      labral capsular ligamentous complex (LCLC). Common patterns of labral injury
      include fraying, flap tears and labral distraction, which can be readily
      identified on both coronal and axial planes by paying attention to signal and
      morphological characteristics. Capsular and ligamentous pathology may be subtle,
      but is recognizable using a high-resolution technique that has differential
      contrast between native intra-articular fluid and the adjacent labrum and
      capsular restraints. Common patterns of capsular injury include a thickened,
      hyperintense capsule, sometimes with disruption and retraction. The inferior
      glenohumeral ligament is the primary stabilizer of the shoulder joint, and
      although failure of this structure is uncommon, the injury is easily identified.
      Shoulder instability is a common presentation, the diagnosis of which is
      dependent upon recognizing various injury patterns including Bankart lesions,
      reverse Bankart lesions, anterior labroligamentous periosteal sleeve avulsion
      (ALPSA) and failure of the inferior glenohumeral ligament.

PMID- 10901953
TI  - Imaging of the normal and abnormal pancreaticobiliary system with single-shot MR
      cholangiopancreatography: a pictorial review.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is a rapidly evolving non
      invasive imaging modality that produces images of the pancreatic duct and biliary
      tree without the need for intravenous or oral contrast. The images are equivalent
      to those from endoscopic retrograde cholangiopancreatography (ERCP), but the non
      invasive acquisition avoids the morbidity and mortality associated with
      diagnostic ERCP. Magnetic resonance cholangiopancreatography is indicated in
      patients who require only a diagnostic ERCP, who fail an ERCP or who are unable
      to undergo ERCP due to altered post-surgical anatomy. Other evolving indications
      include triaging of patients with obstructive jaundice into percutaneous or
      endoscopic management drainage pathways depending on the site, length and nature
      of the duct obstruction, thereby potentially decreasing the number of failed or
      unsuccessful ERCP. Pre-operative identification of anomalous biliary anatomy and
      choledocholithiasis prior to laparoscopic cholecystectomy promise to modify the
      pre-operative and operative management of the patient in order to minimize the
      risk of duct injury and unnecessary intra-operative dissection and
      cholangiography. The advantages of the technique include its non-invasiveness,
      the absence of contrast administration, its relative operator independence and
      the ability to evaluate both sides of an obstructed duct, thereby accurately
      evaluating stricture morphology and length. The disadvantages of MRCP compared to
      ERCP include its lack of an immediate therapeutic solution to duct obstruction,
      procedural cost, unit availability and the inability to evaluate patients with
      pacemakers or ferromagnetic implants.

PMID- 10901954
TI  - Interventional catheter magnetic resonance angiography with a conventional 1.5-T
      magnet: work in progress.
AB  - Magnetic resonance contrast enhancement depends on the relative timing of image
      acquisition. Limited human trials have demonstrated efficacy of intra-arterial
      gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) in delineating vascular
      anatomy with X-rays. The present study assessed the ability of dynamic MR during
      intra-arterial Gd-DTPA administration to demonstrate vascular anatomy compared to
      conventional angiography as the gold standard. As interventional MR techniques
      using dedicated magnets proliferate, the ability to perform invasive MR
      angiography with a conventional magnet would be of great utility at established
      sites. Four subjects referred for different types of angiography underwent
      dynamic MR studies, including one with iliac artery stenting (Palmaz P204,
      Johnson and Johnson). All were examined with conventional angiography, and again
      after dynamic intra-arterial (IA) Gd-DTPA infusion. Coronal MRI images of the
      body were acquired using a 1.5-T superconducting magnet (three with a GE Signa,
      one with Philips NT), fast spoiled gradient echo (FSPGR); echo time (TE) = 4.2
      msec, repetition time (TR) = 68-150 msec, flip = 75 degrees, 0-600 s after dilute
      Gd-DTPA IA bolus injection during sequential breath-hold acquisitions of 13-32 s
      each. All arteries were detected with dynamic MR. The FSPGR MRI with IA Gd-DTPA
      administration can provide adequate time and spatial resolution to demonstrate
      arterial anatomy and arterial stent patency.

PMID- 10901956
TI  - Percutaneous drainage of tuberculous iliopsoas abscesses under image guidance.
AB  - Most intra-abdominal and other types of fluid collections are now successfully
      drained percutaneously under image guidance. The utility of percutaneous drainage
      of tuberculous abscesses, especially those associated with osseous changes, is,
      however, less well established. Six patients with tuberculous iliopsoas abscesses
      were successfully managed by percutaneous drainage combined with antituberculous
      therapy. The abscesses were bilateral in one patient and unilateral in the other
      five. Drainage was by needle aspiration under ultrasound (US) guidance in one
      patient, and by catheter under CT guidance in the other patients. Three patients
      had associated osseous changes. There were no procedural complications.
      Tuberculous iliopsoas abscess can be successfully treated by percutaneous
      drainage and appropriate antituberculous therapy.

PMID- 10901955
TI  - Blunt abdominal trauma: comparison of ultrasonography and computed tomography in
      a district general hospital.
AB  - Ultrasonography has been proposed as a screening method for blunt abdominal
      trauma, but its specific role in comparison with other diagnostic modalities has
      yet to be defined. The aim of the present retrospective study was to compare the
      results of ultrasonography and CT of the abdomen in blunt trauma in a district
      general hospital. The hospital records of 25 patients who were admitted with
      blunt abdominal trauma to Southland Hospital, Invercargill, New Zealand, between
      January 1991 and November 1996 and who had both ultrasound and CT of the abdomen
      within 48 h of admission were reviewed. Ultrasound missed seven lesions in seven
      patients (7/25, 28%) compared with CT. Three of these were intestinal lesions
      that needed laparotomy. Ultrasound had a usefulness index of 1, 0.76, 0.72, 0.69
      and 0, respectively, for detecting lesions of the kidneys, free intraperitoneal
      fluid, the liver, the spleen, and intestines. Although ultrasound can be used as
      an initial screening method for blunt abdominal trauma, CT is still the imaging
      modality of choice for detecting intra-abdominal lesions for stable patients in a
      district general hospital.

PMID- 10901957
TI  - How useful is contrast enhancement after a normal unenhanced computed tomography
      brain scan?
AB  - An audit was performed of contrast use in 400 CT brain scans performed with and
      without contrast enhancement; all 400 scans were re-read by a second reader who
      did not know the result of the original reading. From this initial series 184
      scans were identified in which the unenhanced series had been read as normal by
      both observers. Of these 184 studies, only one enhanced scan showed an
      abnormality, and this lesion is thought to be benign. In conjunction with
      published literature it is concluded that it is reasonable not to give contrast
      if there is a low expectation of a lesion being present, and if the unenhanced
      scan is normal. Protocols are presented for the use of intravenous contrast in CT
      brain scans.

PMID- 10901958
TI  - Haemoptysis in patients with a normal chest radiograph: bronchoscopy-CT
      correlation.
AB  - The exact role of fibre-optic bronchoscopy (FOB) and CT of the chest in the
      diagnosis of patients presenting with haemoptysis and a normal or non-localizing
      chest radiograph has not been clearly defined. A study was designed to evaluate
      50 patients presenting with haemoptysis and a normal or non-localizing chest
      radiograph using FOB and high-resolution computed tomography (HRCT). A definitive
      diagnosis was established in 17 (34%) patients. The aetiologies included
      bronchiectasis (24%), bronchial adenoma (6%), tuberculosis (2%) and bronchitis
      (2%). The diagnosis was made by HRCT in 15 (30%) patients, while FOB was
      diagnostic in five (10%) patients. The diagnosis was made by HRCT and FOB in all
      patients with focal airway abnormalities. Therefore, HRCT effectively delineated
      abnormalities of both the central and peripheral airways. It is concluded that CT
      should be obtained prior to FOB in all patients presenting with haemoptysis and a
      normal or non-localizing chest radiograph.

PMID- 10901959
TI  - Mechanical thrombectomy in acute venous thrombosis using an Amplatz thrombectomy
      device.
AB  - Three cases of percutaneous mechanical thrombectomy using the Amplatz
      thrombectomy device are presented. All cases involve the application of the
      device in a major thoracic or abdominal vein in situations in which
      chemothrombolysis was contraindicated. The method of operation of the Amplatz
      thrombectomy device, as well as a brief overview of its clinical applications,
      are presented.

PMID- 10901960
TI  - Magnetic resonance evaluation of idiopathic scoliosis: a prospective study.
AB  - The objective of the present study was to determine the incidence of unsuspected
      intraspinal pathology and to assess the value of atypical clinical features as
      predictors of these intraspinal pathologies, in patients with idiopathic
      scoliosis. Twenty-five consecutive patients (13 boys, 12 girls) with idiopathic
      scoliosis were prospectively evaluated with MRI. Magnetic resonance imaging
      detected intraspinal pathology in seven patients (28%), which included
      syringohydromyelia with Chiari I malformation (n = 5), and syringomyelia and dumb
      bell neurofibromas in one patient each, respectively. Dural ectasia was also
      present in five patients. Atypical features, described in the literature as
      pointers to intraspinal pathologies such as the age < 11 years at presentation,
      presence of pain, hyperkyphosis, severe curves and the presence of the left
      thoracic or thoracolumbar curves, were seen to be equally distributed between the
      two groups (those with and without intraspinal pathologies), thus raising doubts
      about the importance of these features.

PMID- 10901961
TI  - A magnetic resonance-compatible experimental set-up for hyperthermia studies.
AB  - This study presents the development and testing of an experimental set-up for
      simultaneous measurements of pH (intracellular by MR and extracellular by fibre
      optic pH meter), tumour bio-energetics (by MR), and core/tumour temperatures (by
      thermocouples) in tumour-bearing mice. Potential sources of measurement errors
      when using these techniques concurrently in an MR set-up are discussed. Emphasis
      is placed on simple practical solutions to these problems.

PMID- 10901962
TI  - Primary invasive cancer of the vagina: outcome and complications of therapy.
AB  - The aim of the present study was to review the characteristics of cases of
      vaginal cancer, results of treatment and complications occurring at Westmead
      Hospital over the period 1979-96. International Federation of Gynaecology and
      Obstetrics (FIGO) staging and Eastern Cooperative Oncology Group (ECOG) status
      had been recorded prospectively, while other information was obtained
      retrospectively, including complications using the Franco-Italian Glossary. There
      were 37 eligible patients, 34 of whom were treated radically. Five-year survival
      for stage I was 90%, for stage II it was 50%, and for stage III it was 40%. There
      was only one stage-IV patient. The majority of patients who relapsed did so
      locally (63%). Using the Franco-Italian Glossary 10.8% of patients had, at worst,
      G0 toxicity, 21.6% had G1 toxicity, 29.7% had G2 toxicity, 37.8% had G3 toxicity,
      and no patients had G4 toxicity. Seven patients (18.9%) had a laparotomy for a
      complication of therapy. Excluding the three palliative patients and controlling
      for disease stage, it was found that there was a trend to improved survival in
      patients who had brachytherapy and those who suffered worse complications. While
      results for treatment of early stage vaginal cancer appear good, new techniques,
      particularly those that improve local control, are required for higher stage
      disease.

PMID- 10901963
TI  - Strontium and samarium therapy for bone metastases from prostate carcinoma.
AB  - A review was performed of all patients who received strontium-89 chloride or
      samarium-153 ethylenediamine-tetramethylenephosphonate for prostate cancer
      metastatic to bone at the Royal Brisbane Hospital between 1992 and 1997. There
      were 57 patients, 38 treated with strontium-89 and 19 with samarium-153. Forty
      patients had radionuclide therapy alone, and 28/40 (or 70%) responded in terms of
      experiencing a beneficial effect on pain. In the other 17 patients, the effect of
      the radionuclide on pain could not be assessed because they received external
      beam radiotherapy concomitant with a therapeutic radionuclide. There was no
      difference in response rates between the samarium and strontium groups as
      measured by the effect on pain or in the time to progression. The median time to
      progression for all patients was 2-3 months. The present study confirms that
      following administration of a therapeutic radionuclide, a high proportion of
      patients experienced improvement of pain, but the time to progression is not
      long, so that the overall degree of benefit is modest.

PMID- 10901964
TI  - Targeted alpha therapy: evidence for potential efficacy of alpha-immunoconjugates
      in the management of micrometastatic cancer.
AB  - There can be little doubt that one of the most important problems in the
      management of cancer is control of metastatic disease. This objective must be
      achieved ideally with a systemic therapeutic modality that targets cancer cells
      and gives minimal collateral damage to critical normal cells. The efficacy of
      targeted cancer therapy relies on the ability of a toxin to be located in the
      target cancer cell. The ideal toxin is one that is active only in the cancer
      cell, and not in critical normal cells. Failing this, the next best approach is a
      toxin with a short effective lifetime to target early stage micrometastatic
      disease. This rules out chemical toxins, given that they remain effective until
      excreted from the body, and localization of dose to the cancer cell rules out
      beta-emitting radio-isotopes (RI). Alpha-emitting RI, however, are much more
      appropriate toxins because they are short-lived and because their cytotoxicity is
      the result of their high rate of energy loss and short range of the alpha
      particles. These radionuclides have properties that are particularly suited for
      the elimination of single cells in transit or small nests of cancer cells. In
      vitro and in vivo experiments with alpha RI show dramatic superiority over beta
      RI. Only a few nuclear hits are needed to kill cells, and the formation of
      metastatic lung lesions and subcutaneous lesions in mice can be inhibited by
      systemic administration of alpha emitters. But alpha RI have not been able to
      control solid tumours, for which beta RI are better suited. A small number of
      alpha-emitting radionuclides are currently under investigation. These are terbium
      (Tb)-149, astatine (At)-211, bismuth (Bi)-212 and Bi-213. Terbium-149 and At-211
      both require accelerators in close proximity to the place of application. The Bi
      isotopes are produced by long-lived parents and, as such, can be obtained from
      generators. The first phase-1 dose escalation trial with Bi-213
      radioimmunoconjugate (RIC) commenced in New York in 1997, and other trials are
      planned with At-211 RIC and At-211 methylene blue for melanoma. Actinium (Ac)-225
      is obtained from the decay of thorium (Th)-229, which is a waste product in the
      enrichment of fissile Th-233. Alternative accelerator production routes are being
      investigated, beginning with the European Centre for Nuclear Research (CERN) GeV
      proton spallation source. The ready and low-cost availability of the Ac:Bi
      generator is an important element in the implementation of clinical trials for
      patients with poor prognoses but without evidence of metastatic disease.

PMID- 10901965
TI  - Acute toxicity and cost analysis of a phase III randomized trial of accelerated
      and conventional radiotherapy for squamous carcinoma of the head and neck: a
      Trans-Tasman Radiation Oncology Group study.
AB  - The primary purpose of the present analysis was to assess the feasibility and
      acute toxicity of a pure accelerated fractionation regimen in a cooperative group
      setting. This analysis included the first 320 patients entered on to the Trans
      Tasman Radiation Oncology Group (TROG) randomized controlled trial which compared
      accelerated radiotherapy (ART) with conventional radiotherapy (CRT) in stage III
      and IV squamous cell carcinoma (SCC) of the head and neck. Patients were
      randomized to either 59.4 Gy in 33 fractions over 24 days (ART) or to 70 Gy 35
      fractions over 49 days (CRT) after being stratified for site and stage. Accrual
      began in 1991 and the trial was closed on 3 April 1998 with the targeted 350
      patients. The 3-year survival for the whole group was 54%, and the 3-year disease
      free survival was 41%. Toxicity data were available on 303 patients (148 ART; 155
      CRT). Mucosal toxicity was worse in the accelerated arm, and it peaked
      approximately 3 weeks earlier than the conventional arm. Skin toxicity was
      equivalent but occurred approximately 7 days earlier in the accelerated arm.
      Acute effects in both arms healed completely. Hospitalization was more common in
      the ART arm (71 vs 52 patients; P = 0.01) but the total bed days in hospital was
      not greatly different (1707 bed days for ART and 1607 bed days for CRT). Patients
      were more likely to require nasogastric (NG) feeding in the ART arm (49 vs 33
      patients; P = 0.02). There were 1157 NG feeding days for ART and 1154 NG feeding
      days for CRT. The average cost of radiation treatment per patient including
      hospitalization, NG feeding and accommodation was $11,750 in the ART arm and
      $11,587 in the CRT arm. The accelerated arm has been shown to be a tolerable,
      practical and cost-equivalent regimen. The assessment of the therapeutic ratio of
      this accelerated protocol (ART) will be determined when the analysis of late
      effects and loco-regional control is made when the data are more mature.

PMID- 10901966
TI  - High-energy electron and photon therapy to the parotid bed: radiation dose
      perturbations with a titanium mandibular implant.
AB  - Adjuvant radiation therapy to the parotid bed is commonly administered following
      surgical resection using either a pair of angled wedged photon beams or an
      ipsilateral mixed-beam portal of electrons and photons. The present study seeks
      to determine the optimal parotid bed treatment technique in the presence of a
      titanium mandibular implant by investigating perturbations in the dose
      distribution deep to this implant for a 15-MeV electron beam and a 6-MV photon
      beam. A titanium mandibular plate was embedded in a tissue-equivalent phantom,
      and irradiated with 15-MeV electrons, and 6 MV photons. Radiation doses behind
      the plate were measured with both thermoluminescent dosimeters and radiographic
      film. With 15-MeV electrons, there is a clinically significant decrease in the
      dose beyond the titanium plate, which is most important at 5-mm and 10-mm depths
      (18-27%). With 6-MV photons the dose at the deep interface of titanium and tissue
      is reduced by between 15 and 18%, but rapidly drops to < 5% at a depth of 5 mm.
      In adjuvant treatment to the parotid bed, when the clinical target volume
      includes tissue positioned deep to a titanium implant, significant underdosage
      occurs with ipsilateral beam arrangements, especially when electrons are used.

PMID- 10901967
TI  - An Australasian assessment of the basic treatment equivalent model derived from
      New South Wales data.
AB  - The current method of assessment of radiation oncology linear accelerator
      throughput is either by patients per unit time or fields per unit time. This,
      however, does not take into consideration the complexity of different treatment
      techniques or of casemix. A model has been developed in an earlier study, called
      'basic treatment equivalent' (BTE), to measure patient throughput of a linear
      accelerator, which includes consideration of the complexity of treatment
      techniques. The present study compared the BTE model with the current best
      measure of patient throughput of fields per hour. All 37 departments in Australia
      and New Zealand were invited to participate in testing the model, and 36 agreed
      to participate. The study period for each department was a consecutive 4 weeks
      between August and December, 1996. The prospective data collected were the total
      BTE units treated per linear accelerator per day, the total number of patients
      and fields treated per linear accelerator per day, and the total linear
      accelerator hours of operation per day excluding calibration time and significant
      breaks of linear accelerator time such as planned meal breaks. The treatment
      breaks between consecutive treatment fractions were not excluded from the linear
      accelerator treatment time. The throughput data for 36 departments (92 linear
      accelerators) were collected over the 4-week study period. The average throughput
      for the departments was 10.8 fields per hour and 4.2 patients per hour. The
      average BTE per department was 5.7 BTE per hour. The average BTE per episode per
      department was 1.38. The BTE model was found to be a more sensitive measure of
      productivity compared with fields per hour (P < 0.001). Some treatment techniques
      were thought to be not well represented by the BTE formula, particularly those
      techniques where junctions were present. The BTE model is a more sensitive
      measure than fields per hour and better reflects the variations in complexity in
      techniques. Despite this result there is further refinement to be performed to
      make the model even more sensitive.

PMID- 10901968
TI  - Refinement of the basic treatment equivalent model to reflect radiotherapy
      treatment throughput using Australasian data.
AB  - A model of radiotherapy linear accelerator throughput has been developed and
      shown to be a more sensitive measure of throughput than current measures of
      throughput. The present study aims to develop a more sensitive basic treatment
      equivalent (BTE) model that still measures linear accelerator throughput and
      considers some of the shortcomings of the previous model. All radiation oncology
      departments in Australia and New Zealand were invited to participate. Departments
      were asked to time with a stopwatch all episodes of radiotherapy treatment over a
      4-week period. Data collected for each treatment fraction included treatment
      intent, tumour site, patient age, Eastern Cooperative Oncology Group (ECOG)
      performance status, number of fields used, number of wedges used, number of
      junctions, number of shielding blocks used, whether the treatment was the first
      fraction, the use of general anaesthesia and whether port films or electronic
      portal imaging was used. Twenty-six departments of radiation oncology (70%)
      participated in this trial. A total of 7929 fractions of treatment, administered
      to 2424 patients, were timed. The factors found to most significantly impact on
      treatment duration on multivariate analysis were the type of fraction (first
      fraction was longer than subsequent fractions), type of beam (electrons were
      quicker than photons, which were quicker than mixed), number of fields, number of
      shields, number of junctions, number of port films and performance status (ECOG <
      2 vs > 2). The age of the patient, number of compensators and the sex of the
      patient were not significant. The relationships between factors were assessed,
      and models of measuring linear accelerator throughput which consider complexity
      corrections were derived. It is possible to show that linear accelerator
      throughput is poorly measured by just considering numbers of patients or fields
      treated per unit time; and that other factors that impact on treatment duration
      must be considered. A more sensitive model of patient throughput is suggested;
      but even when a large number of factors are considered, some insensitivity still
      remains in the model.

PMID- 10901969
TI  - Pre-operative management of congenital choledochal cyst with ultrasound-guided
      percutaneous choledochalcystostomy.
AB  - Choledochal cyst is a rare congenital anomaly of the biliary system, presenting
      in infancy. Two cases of choledochal cyst (one infected) with grossly deranged
      liver function tests and associated biliary atresia, which were successfully
      managed pre-operatively by sonoguided percutaneous choledochalcystostomy, are
      reported here. The use of this technique in the treatment of patients such as
      these is proposed.

PMID- 10901970
TI  - Osteosarcoma of the sella.
AB  - Primary osteosarcoma of the skull is rare. Osteosarcoma arising from the sellar
      region is extremely uncommon. The case of a 38-year-old man with osteosarcoma of
      the sella is described, and the literature is reviewed. The patient was treated
      with surgery followed by aggressive chemotherapy and radiotherapy. Currently he
      is in remission at 12 months.

PMID- 10901971
TI  - Carcinosarcoma of the parotid gland: ultrasound and computed tomography findings.
AB  - Carcinosarcoma is a rare tumour of the salivary gland. The ultrasound and CT
      appearances of a rapidly enlarging carcinosarcoma in the parotid are described.
      Both modalities revealed a 4-cm tumour with relatively benign features and no
      evidence of lymphadenopathy. Ultrasound showed a well-defined mass of homogeneous
      low echogenicity and posterior acoustic enhancement. Computed tomography showed a
      parotid mass of homogeneous attenuation similar to muscle, and homogeneous
      enhancement following contrast. The clue to the malignant nature of the lesion
      was a short indistinct superficial margin with tumour extension into the adjacent
      subcutaneous tissues.

PMID- 10901972
TI  - Racemose cysticercosis: novel demonstration of a rare condition.
AB  - A case of cisternal cysticercosis (racemose type) is presented which was well
      demonstrated on MRI by intrathecal administration of gadodiamide (gadolinium DTPA
      BMD). The cysts appeared as multiple filling defects within an opacified
      cerebrospinal fluid. The authors believe that this is the first time that
      cisternal cysticercosis has been demonstrated using this technique.

PMID- 10901973
TI  - Methanol poisoning: brain computed tomography scan findings in four patients.
AB  - Methanol, through its chief metabolite, formate, causes irreversible neurological
      damage. Methanol intoxication produces classic neuropathological changes and
      characteristic imaging findings. Computed tomography was performed on four
      patients who presented with a history of methanol poisoning. Prominent, hypodense
      lesions in the lentiform nuclei and peripheral white matter, sometimes with
      haemorrhage, were the characteristic imaging findings in the present patients. It
      was noted that the severity and extent of necrosis of the lentiform nuclei do not
      necessarily correlate with the clinical outcome.

PMID- 10901974
TI  - Fluid-fluid levels in intracranial schwannomas.
AB  - Intracranial cystic neurogenic tumours constitute an uncommon subset of tumours
      with a distinct clinico-biological behaviour. The presence of fluid-fluid levels
      within the tumours, although rare, confirms the cystic nature of the neoplasms.
      Barring the acoustic schwannomas, cystic cranial nerve schwannomas are
      exceptionally uncommon. Imaging findings of fluid-fluid levels in two non
      acoustic cranial nerve schwannomas are described; one was a cystic trigeminal
      schwannoma and the other was a glossopharyngeal nerve schwannoma. The causes of
      the fluid-fluid level and its implications are analysed.

PMID- 10901975
TI  - Congenital mesoblastic nephroma: other magnetic resonance imaging findings.
AB  - Congenital mesoblastic nephroma (CMN) is a rare renal tumour usually imaged by
      ultrasound and or CT. To the authors' knowledge there have been only two previous
      reports concerning MR imaging of CMN in the English-speaking literature. The MRI
      findings in a neonate with CMN, which were not previously described, are reported
      here.

PMID- 10901976
TI  - Diffuse lymphangiomatosis of bone.
AB  - Two cases of lymphangiomatosis of bone, a very rare systemic condition
      characterized by both skeletal and parenchymal lesions, are presented. The
      skeletal changes have an appearance similar to haemangiomas in the spine, and
      soap-bubbly lesions in the flat bones. One case carried the diagnosis of
      eosinophilic granuloma for 18 years. The findings on MRI, which have not been
      previously well-established, are discussed.

PMID- 10901977
TI  - Pulmonary hydatid disease mimicking sequestration: differentiation on magnetic
      resonance imaging.
AB  - A case of hydatid disease of the lung proven by thoracotomy and histopathological
      evaluation is described. It was clinically and radiologically suggestive of a
      complicated pulmonary sequestration or non-resolving consolidation.

PMID- 10901978
TI  - Computed tomography demonstration of a fat-fluid level in tuberculous chylous
      ascites.
AB  - The occurrence of fat-fluid levels in ascites, although rare, is pathognomic of
      chylous ascites. The ultrasound and CT scan findings of a fat-fluid level in the
      ascitic fluid of a patient with abdominal tuberculosis are described here.
      Recognition of this important sign, in conjunction with other ancillary findings
      of abdominal tuberculosis, assist in establishing the correct diagnosis. Anti
      tuberculous chemotherapy suffices in treating the condition, thus obviating the
      need for surgical intervention.

PMID- 10901980
TI  - Spontaneous intracranial hypotension.
AB  - Spontaneous intracranial hypotension is a rare benign and usually self-limited
      condition of unknown aetiology. Four cases are presented that illustrate how the
      MRI features may support a diagnosis suggested on clinical grounds. The MRI
      findings include diffuse symmetric smooth dural thickening and enhancement, not
      only at the cranial level, but also involving the cervical spinal dura, subdural
      effusions and downward displacement of the cerebellar tonsils.

PMID- 10901979
TI  - Metaphyseal chondrodysplasia, type Jansen.
AB  - The Jansen type of metaphyseal dysplasia is a rare disorder with significant
      clinical and radiographic variability. Two cases of classical Jansen disease and
      one with some distinctive features suggestive of the Jansen variant are reported.

PMID- 10901982
TI  - Mycobacterium avium complex spinal epidural abscess in an HIV patient.
AB  - Although Mycobacterium avium complex (MAC) is the most common opportunistic
      bacterial infection in AIDS patients, epidural involvement is rare. A case of MAC
      spinal epidural abscess without vertebral osteomyelitis, that was continuous with
      presacral and bilateral piriformis muscle inflammation, is reported.

PMID- 10901981
TI  - Inguino-scrotal hernia detection in the early phase of a bone scan.
AB  - A case report of a large inguino-scrotal hernia detected in the early phase of a
      radionuclide bone scan is presented.

PMID- 10901983
TI  - Tattoo allergy in patients receiving adjuvant radiotherapy for breast cancer.
AB  - Tattooing is routinely employed prior to radiotherapy treatment but allergies to
      tattoos are rare. New information on the incidence of tattoo allergy at St George
      Hospital is presented with details of two clinical cases. The literature on
      tattoo allergy has been unable to estimate the incidence of allergic reaction to
      tattoos because the total number of patients treated is unknown and not all
      patients were followed up. Our radiation oncology population for the first time
      has provided a known denominator, but wide confidence intervals prevent an
      accurate estimate of the incidence. Salient issues about tattoo allergy are
      highlighted based on a review of the published literature from 1966 to 1998.

PMID- 10901984
TI  - Don't block the new kids.

PMID- 10901986
TI  - Analysis and quantification of mental stress and fatigue using Maxwell relations
      from thermodynamics.
AB  - Several experimental and theoretical techniques have been developed to analyze
      both physical and psychological stresses. These techniques have relied mainly on
      certain parameters based on physiological, behavioral, and performance related
      data. This study is based on a thought experiment which describes the technique
      to quantify mental stress based on physiological responses using the entropy
      concept. It relates different physiological parameters using the Maxwell
      relations of thermodynamics with a systems approach. Data for testing this
      analytical approach were obtained from an experimental study which was conducted
      to determine the effects of a mentally stressful situation (final examination) on
      the common physiological responses (blood pressure, pulse rate, and oral body
      temperature) of students. The results indicated that the imposed mental stress
      causes significant changes in physiological responses. The Maxwell relations of
      thermodynamics were used to quantify the level of stress under different
      conditions. The results obtained from these relations validated the principles of
      thermodynamics as applied to the human system.

PMID- 10901985
TI  - What is the minimum age for applying the forbes equation between body density and
      body fat to the elderly?
AB  - In order to determine the age above which the FORBES equation for calculating
      percent body fat (%BF) in the elderly is to be applied, 9 persons in their 60s, 7
      persons in their 70s and 3 persons older than 80 took part in this study. %BF was
      measured using dual-energy X-ray absorptiometry (DEXA). In each subject, body
      density was measured using densitometry. %BF was then calculated by substituting
      body density for the Siri or FORBES equation. Based on the value of %BF measured
      with DEXA, the calculated %BF was criticized for each decade of subjects. It was
      concluded that the Siri equation should be applied to those who are younger than
      80 and that the FORBES equation should be applied to those who are 80 and older.

PMID- 10901987
TI  - The real life of aged persons living alone in a depopulated area--in case of
      village a in Nagano Prefecture.
AB  - Japan adopted a high economic growth policy and developed rapid industrialization
      since the 1960s. Consequently, Japanese have gotten various positive influences
      and negative influences. In this paper, we describe various positive influences
      and also we describe the "real life" of aged persons living alone in depopulated
      areas as one of the typical negative influences. For the purpose of investigating
      the actual lives of aged person living alone in depopulated areas, we carried out
      repeated interviews, research and direct observations of their work and lives in
      Village A. Village A is located in a mountain area 20 kilometers from Nagano
      City. The total population of the village was 3,294 in 1993, while it was 6,312
      in 1960. The ratio is increasing rapidly year by year. In the village, the number
      of aged persons over 65 years old living alone, without any family, was 116 in
      1994. The highest age is 94 years old. The number is increasing year by year.
      Through our study, it is made clear that aged persons over 65 years old living
      alone in the village have to manage everything in their daily lives by themselves
      to maintain their own safety, while accepting the influences of economic and
      industrial developments.

PMID- 10901988
TI  - Effectiveness of noise barriers on an interstate highway: a subjective and
      objective evaluation.
AB  - The objective of this study was to determine the actual and perceived
      effectiveness of noise barriers along interstate highways. Using a 5-mile section
      of Interstate 71 in the greater Cincinnati area as the study area, traffic noise
      readings and opinions of residents living along the sections of the highway were
      recorded. Noise readings were taken before and after the noise barriers were
      erected. A questionnaire was designed to elicit noise-related annoyance of the
      residents in the areas adjoining the highway. The results indicated that, in
      general, noise barriers were effective as indicated by a reduction in noise
      levels by as much as 11 dBA. The barriers, however, failed to bring noise levels
      for locations closer to the highway within the levels desired by the government
      (67 dBA). Most residents living right next to the highway were very satisfied
      with the installation of noise barriers. In general, these individuals felt that
      the quality of life improved with the noise barrier installation. The same,
      however, was not true of residents living a few blocks away from the highway-
      they felt the noise barriers were a waste of money. There was no significant
      difference in traffic noise pattern during the weekdays or weekends. Noise
      readings taken in two different locations were observed to be similar.

PMID- 10901989
TI  - Ergonomic design of a barber's workstation.
AB  - Long hours of work while standing have been known to cause health problems for
      humans. Such professions include that of the barber. A survey was conducted of
      barbers from different barber shops in Saudi Arabia to determine their discomfort
      level. A prototype workstation was then designed and constructed in which the
      barber sits and performs work. The workstation was tested by nine barbers in the
      Human Factors Laboratory in the Systems Engineering Department at King Fahd
      University of Petroleum and Minerals. These barbers were among those surveyed
      earlier in their shops. Their discomfort level was again taken and an experiment
      was conducted to design the shape of the footrest. The discomfort levels obtained
      while standing and sitting were statistically analysed. From the results, it was
      concluded that the mean of the discomfort levels while standing is significantly
      (alpha = 0.01) higher than that while sitting.

PMID- 10901990
TI  - Thermophysiological responses under the influences of two types of clothing at an
      ambient temperature of 32 degrees C with sun radiation.
AB  - This study aimed to examine the different thermophysiological responses between
      two types of clothing (HALF, shirts with half sleeves and knee-length trousers;
      and LONG, shirts with long sleeves and long trousers) in a warm environment with
      artificial sun radiation. Seven females volunteered as subjects. The subject sat
      on a balance for 1 h in a climatic chamber with artificial sun. The artificial
      sun radiation was 600 kcal.m-2.h-1 in front of the subject. The ambient
      temperature was increased gradually from 27 to 31 degrees C over the experimental
      period. The globe temperature also increased from 27 to 43 degrees C in 15 min
      and was kept at 44 degrees C on additional 45 min. The main results were
      summarized as follows: 1) Extent of rise in rectal and mean skin temperatures
      during 1 h exposure was significantly higher in HALF than in LONG. 2) Local sweat
      rate was greater in HALF. 3) The subjects felt wetter and less comfortable in
      LONG. These results suggest that LONG could weaken heat stress when the subjects
      were exposed to sun radiation even under moderate warm ambient temperature.

PMID- 10901991
TI  - Effects on sleep patterns during simulated oxygen-helium saturation diving at 180
      and 230 m.
AB  - The standard polysomnography of four divers was recorded respectively through 188
      nights in two simulated experiments under a hyperbaric saturation environment of
      He-O2 mixture at the depths of 180 and 230 m. In the two diving conditions on the
      bottom nights and decompression nights, the following was shown: A reduction of
      total sleep time, a decrease of sleep efficiency; an increase of sleep latency,
      frequency of wake after sleep, number of sleep stage shifts, and a lengthening of
      stage 1 sleep; and a reduction of stage 4 sleep. In the 230 m-diving condition on
      the bottom nights and the decompression nights, only stage 4 sleep showed a
      significant decrease when compared with the 180 m-diving condition. It is assumed
      that both were conditions in which awakening was likely to happen and there would
      be no disorders of fundamental sleep patterns.

PMID- 10901992
TI  - Basic study on the rectangular numeric keys for touch screen.
AB  - The present study was conducted to examine the optimum inter-key spacing of
      numeric rectangular keys for touch screens. Six male students (22-25 years old)
      and three female students (21-24 years old) participated in the experiment. Each
      subject performed the data entry task using rectangular keys of touch devices.
      These keys were arranged in both horizontal and vertical layouts. The sizes of
      the rectangular keys in both layouts were 12 x 21 mm and 15 x 39 mm, and each of
      the inter-key spacing of each key was 0, 3, 6, 12 and 21 mm. The response time
      with inter-key spacing of 3 mm was significantly faster than with the inter-key
      spacing of 0, 12 and 21 mm (p < 0.05). Keys of vertical position produced faster
      response time than that of horizontal position. The subjective ratings showed
      that the inter-key spacing of 6 mm was significantly better than the inter-key
      spacing of 0, 3, 12 and 21 mm (p < 0.05).

PMID- 10901993
TI  - Characteristics of physical health conditions in middle-aged and elderly joggers.
AB  - To clarify the characteristics of physical health conditions in middle-aged and
      elderly joggers who run regularly, they were compared with middle-aged and
      elderly people who did not exercise routinely. The physical health conditions
      were investigated by a questionnaire survey sent by mail. The subjects were 316
      joggers (230 men and 86 women) and 272 non-joggers (173 men and 99 women). The
      number of joggers having any illness was lower than that of non-joggers in both
      men and women. In contrast, there was no significant difference in type of
      illness between joggers and non-joggers. Concerning symptoms, the number of
      joggers who complained of lumbar pain and shoulder stiffness was low, but the
      number of joggers with symptoms including knee joint pain and muscle pain as well
      as injury was high compared to non-joggers. While the results of this study
      reconfirm that continuous jogging in middle-aged and elderly people may
      effectively improve their physical condition, based on the finding that the
      morbidity was low, it appears that many joggers have knee joint pain, a typical
      disorder due to running.

PMID- 10901994
TI  - Gd2OSe2

PMID- 10901995
TI  - CsTiP2O7

PMID- 10901996
TI  - Lanthanum selenite, La2(SeO3)3

PMID- 10901997
TI  - beta-K2Cr2O7

PMID- 10901998
TI  - RbLi2Ga2(BO3)3

PMID- 10901999
TI  - (eta 6-hexamethylbenzene)(mesidine)ditriflatoruthenium(II)

PMID- 10902000
TI  - The bis(eta 5-cyclopentadienyl)methylzirconium(IV)
      methyltris(pentafluorophenyl)borate ion pair

PMID- 10902001
TI  - Polymeric bis(glycolato)cobalt(II)

PMID- 10902002
TI  - K2

PMID- 10902003
TI  - Disodium tetrakis(hexanoato-O)zinc(II)

PMID- 10902004
TI  - 20-dicyanomethylene-5,8,11,14-tetraoxa-2,17-dithiabicyclo

PMID- 10902005
TI  - Manganese mercury thiocyanate (MMTC) glycol monomethyl ether

PMID- 10902006
TI  - Monomeric bis(2,4-pentanedionato)cobalt(II)

PMID- 10902007
TI  - (4,4'-bipyridine)dichloromanganese(II), a two-dimensional coordination polymer

PMID- 10902008
TI  - cis-[(4R,5R)-4,5-bis(aminomethyl)-2,2-dimethyl-1,3-dioxolane-N,N']- (malonato
      O,O')platinum(II), an anticancer agent.

PMID- 10902009
TI  - The NiII, HgII and CuII complexes of 12-membered-ring mixed-donor macrocycles

PMID- 10902010
TI  - (12-hydroxymethyl-5,5,7,12,14-pentamethyl-1,4,8,11-tetraazacyclo- tetradecane-N
      acetato-N,N',N",N"',O,O')cobalt(III) chloride perchlorate monohydrate

PMID- 10902012
TI  - Bis(ferrocenium) bis

PMID- 10902011
TI  - Tris(ethylenediamine-N,N')cobalt(III) oxalate perchlorate dihydrate

PMID- 10902013
TI  - (Piperidine-1-carbodithioato-S,S')bis(triphenylphosphine-P)gold(I)

PMID- 10902014
TI  - Diamminebis(2,4,6-tribromophenolato-O)copper(II)

PMID- 10902015
TI  - Interaction between a dimethylamino group and an electron-deficient alkene in
      ethyl (E)-2-cyano-3-(8-dimethyl-amino-1-naphthyl)propenoate

PMID- 10902016
TI  - 1,4,4-trimethyl-9-phenyl-8-oxa-9-aza-bicyclo

PMID- 10902017
TI  - (E)-2-methyl-5-(1-naphthylmethyl)cinnamic acid

PMID- 10902018
TI  - Hydrogen bonds and C-H...O interactions in 2,2'-dimethoxybiphenyl-5,5'-dimethanol
      at 150 K

PMID- 10902019
TI  - Bis(4-nitrophenyl) disulfide at 150 K, a three-dimensional framework built from C
      H...O hydrogen bonds and aromatic pi...pi stacking interactions

PMID- 10902020
TI  - N-nitrosomelatonin

PMID- 10902021
TI  - Two strained hexahelicenophanes

PMID- 10902022
TI  - 2-(2-pyridylimino)-2H-1,2,4-thiadiazolo

PMID- 10902023
TI  - Conformational preferences in 2-nitrophenylthiolates: S-(2-nitrophenyl) 4
      toluenethiosulfonate

PMID- 10902024
TI  - A second monoclinic polymorph of S-(4-tolyl) 4-toluenethiosulfonate at 150 and
      293 K

PMID- 10902025
TI  - An oxazol-5(4H)-one from benzyloxycarbonyl-(Aib)4-OH

PMID- 10902026
TI  - 4-hydroxy-ONN-azoxybenzene

PMID- 10902027
TI  - Octa-O-acetyl-beta,beta-thiotrehalose.

PMID- 10902028
TI  - Methyl 4-O-beta-L-fucopyranosyl alpha-D-glucopyranoside hemihydrate.
      lerik@struc.su.se.

PMID- 10902029
TI  - 2-(1,3-dithian-2-yl)benzaldehyde and N-[2-[2-(1,3-dioxan-2
      yl)phenoxy]ethyl]phthalimide.

PMID- 10902030
TI  - Intermolecular interactions and molecular geometry in molecular complexes of N,N
      dimethylaniline: the 1:1 complex with 1,2,4,5-tetracyanobenzene.

PMID- 10902031
TI  - New limonoids from Harrisonia perforata (Blanco) Merr.

PMID- 10902032
TI  - The conversion of a pyrrole trimer derivative into a 4,5,6,7-tetrahydro-4-(pyrrol
      2-yl)indol-7-yltosylaminoindole

PMID- 10902033
TI  - Self-assembly of 2-pivaloyl-6-chloropterin

PMID- 10902034
TI  - 1,4-bis(2-benzimidazolyl)benzene

PMID- 10902036
TI  - 1-tert-butyl-2-methylphospholane-borane and its coupling product 2,2'-bis(1-tert
      butylphospholane-borane)

PMID- 10902035
TI  - Zwitterionic pyrrolidine-2,2-diylbis(phosphonic acid) at 100, 150 and 293 K.

PMID- 10902037
TI  - The oxidized form of nicotinamide adenine dinucleotide.

PMID- 10902038
TI  - Alcohol and its relation to all-cause and cardiovascular mortality.
AB  - There exists a considerable body of evidence indicating that light-to-moderate
      alcohol consumption is associated with a reduced mortality from ischaemic heart
      disease (IHD). However, an L-shaped saturation curve has been observed in many
      prospective studies on alcohol consumption and IHD mortality. No further risk
      reduction is expected if more than 30 grams of ethanol per day is consumed. In
      ecological studies, particularly wine showed a strongly negative correlation with
      IHD mortality. This possible specific effect of wine has not yet been confirmed
      in observational prospective studies. The evidence found in the ecological
      studies may partly be explained by several healthy dietary habits associated with
      wine drinking. Although the results of the prospective studies are less
      consistent for stroke mortality, the largest risk reduction was observed among
      the drinkers with 10-20 grams of ethanol per day, and then the risk increased.
      However as an opposite effect of alcohol is expected to ischaemic and
      haemorrhagic stroke, further studies with consideration to the type of stroke are
      needed. Several prospective studies demonstrated a J-shaped curve between alcohol
      consumption and all-cause mortality both in men and women. It is usually
      explained by a risk reduction of mortality from IHD and stroke among light
      drinkers. Considering that the risk reduction for all-cause mortality is limited
      in light-to-moderate drinkers and the reduction is small and that heavy alcohol
      consumption has an apparently harmful effect, a general increase in alcohol
      consumption at the population level is not recommended.

PMID- 10902039
TI  - Clinical value of vectorcardiography, Holter monitoring and quantitative
      electrocardiology. Belgian Society of Cardiology. Working Group on
      Electrocardiology, Exercise Testing and Cardiac Rehabilitation.
AB  - This a position paper of the Working Group on Electrocardiology, Exercise Testing
      and Cardiac rehabilitation of the Belgian Society of Cardiology (BSC), aimed at
      reassessing the value for the clinical practice of cardiology of some
      electrocardiological techniques such as vectorcardiography and Holter monitoring
      in the frame of what has been called "quantitative electrocardiology". This
      official statement issued on behalf of the BSC was deemed necessary because of
      several consecutive attempts to discredit the clinical merits of these
      electrocardiological techniques currently in use in our country. This paper will
      also reassess the role of quantitative electrocardiology amidst non-invasive
      diagnostic methods used for cardiac imaging.

PMID- 10902040
TI  - Heart rate variability and the outcome of head-up tilt in syncopal children.
AB  - OBJECTIVE: This study evaluated autonomic nervous system function in 5 young (6
      10 years old) and 5 older (10-15 years) children with recurrent episodes of
      neurally mediated syncope and a positive tilt-test result, 10 with syncope but a
      negative test result and 30 age-matched healthy volunteers. METHODS: Time- (SDNN,
      SDNNi, SDANNi, rMSSD, pNN50) and frequency-domain indices (LF, HF, LF/HF) of
      heart rate variability (HRV) were measured during a 24-hour Holter recording and
      for 5 min. segments before and during 90 degrees head-up tilt (tests lasted 30
      min. or until syncope occurred). RESULTS: 24-hour HRV-indices were within the
      normal range for all syncopal patients. Mean RR interval and HRV-indices, except
      LF/HF, were higher in the older children with a positive test result before they
      were tilted and during the first 5 min. of head-up tilt. HRV-indices tended to be
      lower after tilt in the younger children with a positive test result. SDNN and LF
      in older children with a positive test result and LF/HF in the younger ones
      increased during the 5 min preceding the syncope. No difference was observed
      between syncopal children with a negative test result and controls. CONCLUSION:
      This study confirms that patients with vasovagal syncope have no chronic
      differences from normal subjects in autonomic nervous system activity. The
      modulation of the autonomic tone during head-up tilt is abnormal in children who
      faint during the test, but younger and older patients respond differently to the
      orthostatic stimulus.

PMID- 10902041
TI  - Stenting of the left main coronary artery. Local experience in Liege.
AB  - We examined the immediate and long-term outcome after stenting of the left main
      coronary artery (LMCA) in 41 consecutive patients who had been considered
      unsuitable for coronary artery bypass graft surgery (CABG). The procedure was
      elective in thirty-two patients (78%) with a protected LMCA in 24 patients and
      non-protected LMCA in 8 patients; the procedure was acute in the setting of
      myocardial infarction or complication of a diagnostic angiography in 9 patients
      (22%). The mean follow-up duration was 19 +/- 13 months. There were 5 in-hospital
      and 3 late deaths; repeat angioplasty was performed in 5 cases, but only one for
      LMCA restenosis. Results varied considerably depending on the clinical
      presentation. For acute patients, technical success was achieved in 89%, survival
      at hospital discharge was 44% and there was no cardiac event at the late follow
      up. For elective patients, technical success was achieved in 100%, survival at
      hospital discharge was 96% and 90% at follow-up. The results of our study suggest
      that when patients have surgical risks, elective LMCA stenting either protected
      or unprotected may be undertaken with a high procedural success rate and a
      favourable clinical late follow-up.

PMID- 10902042
TI  - Complications associated with percutaneous placement of intra-aortic balloon
      counterpulsation: can unsheathed insertion reduce limb ischaemia?
AB  - Complications related to percutaneous placement of intra-aortic balloon pump
      counterpulsation are still high despite major refinements in catheter design and
      techniques. One hundred and forty-eight patients in whom intra-aortic balloon
      pumping was inserted were classified into two groups on the basis of the
      insertion technique. Group I included 103 patients in whom the conventional
      percutaneous insertion was used. A sheathless insertion technique was used in
      group II (n = 45). The overall complication rate was 16.6% (25 of 150), in which
      lower limb ischaemia was the most common complication. The limb ischaemia was
      noted in 12 patients (11.5%) in group I and 4 patients (8.9%) in group II
      (statistically not significant). Peripheral vascular disease, diabetes mellitus
      and female gender were found to be significant predictors of limb ischaemia (p =
      0.01, p = 0.02 and p = 0.03, respectively). In conclusion, sheathless insertion
      of intra-aortic balloon pump catheters does not reduce the incidence of limb
      ischaemia.

PMID- 10902043
TI  - The effect of autonomic nervous system activity on exaggerated blood pressure
      response to exercise: evaluation by heart rate variability.
AB  - OBJECTIVE: We investigated the effect of autonomic nervous system activity on
      exaggerated systolic blood pressure (SBP) response to exercise in healthy
      subjects using heart rate variability (HRV) analysis. METHOD AND RESULTS: We
      studied 53 healthy volunteer subjects with exercise treadmill test according to
      the Bruce protocol. Time domain and frequency domain of HRV were measured for
      each 5-minute segment before (rest) and after exercise (recovery) and during the
      total exercise period. The mean change in SBP (delta SBP) was 39 +/- 18 mm Hg.
      The delta SBP above the value of mean (> or = 40 mm Hg) was defined as an
      exaggerated delta SBP. According to the delta SBP, subjects were classified into
      two groups. Group I consisted of 32 patients who showed a normal delta SBP, group
      II consisted of 21 patients who showed exaggerated delta SBP. There were no
      significant differences in baseline clinical characteristics and exercise
      duration between the two groups. There were no significant differences in the
      mean RR intervals, SDNN (standard deviation of all RR intervals), RMSSD (the
      square root of the mean of the sum of the squares of differences between adjacent
      RR intervals), and HF (high-frequency power, 0.15 to 0.40 Hz) at rest between the
      two groups. However, LF (low-frequency power, 0.04 to 0.15 Hz) and LF/HF ratio at
      rest were significantly higher at rest in group II than in group I. There were no
      significant differences in the mean RR intervals and HF at exercise between the
      groups. However, SDNN and RMSSD were significantly lower, LF and the LF/HF ratio
      were significantly higher at exercise in group II than in group I. No differences
      in these parameters were observed at recovery between the two groups.
      CONCLUSIONS: The sympathetic activity was higher at rest and during the total
      exercise period, parasympathetic activity was lower during the total exercise
      period in healthy subjects with exaggerated SBP response to exercise than in
      those with normal SBP response.

PMID- 10902044
TI  - Primary versus rescue percutaneous coronary intervention in patients with acute
      myocardial infarction.
AB  - OBJECTIVE: To compare angiographic and clinical outcomes of patients with acute
      myocardial infarction (AMI) who underwent primary percutaneous coronary
      intervention (PCI) versus rescue PCI following failed thrombolysis. BACKGROUND:
      Patients presenting with AMI are treated either with primary PCI or with
      thrombolysis. When thrombolysis fails, rescue PCI is performed. METHODS AND
      RESULTS: We compared the outcome of 105 consecutive patients with AMI who
      underwent either primary PCI (60 patients) or rescue PCI (45 patients) between
      January 1997 and January 1999. The patients were followed for up to 6 months.
      Time delay to reperfusion was significantly longer in the rescue PCI group (354
      vs. 189 min; p < 0.001). The majority of patients received a stent (93%).
      Glycoprotein (GP) IIb/IIIa inhibitors were used in 53% of patients in the primary
      PCI group and in 22% in the rescue group. TIMI grade 3 flow was achieved in 93.3%
      of patients in the primary PCI group and in 88.8% in the rescue group (p = 0.08).
      Post-procedure ejection fraction was 53% in the primary PCI group and 47% in the
      rescue group (p = 0.014). A composite endpoint of death, recurrent MI, repeat
      PCI, coronary artery bypass grafting (CABG) and recurrent angina at 6 months
      occurred in 35% of the patients in the primary PCI group and 26.7% in the rescue
      group (p = 0.36). CONCLUSION: Despite a significant delay to reperfusion and a
      lower immediate post-procedure ejection fraction, the clinical outcome of
      patients treated with rescue PCI following failed thrombolysis appears to be
      similar to that of patients treated with primary PCI at 6 months.

PMID- 10902046
TI  - Diagnosis of a coronary artery fistula thirty years after myectomy for septal
      hypertrophy.
AB  - A 61-year-old asymptomatic male patient was evaluated before abdominal surgery.
      He has a history of septal myectomy in 1969 and an episode of atrial flutter in
      1983. On auscultation an atypical murmur was heard. By transthoracic
      echocardiography the diagnosis was made of a coronary artery fistula after septal
      myectomy. We discuss the prevalence, diagnosis and natural history of coronary
      artery fistulas. In our patient we followed a conservative strategy.

PMID- 10902045
TI  - Positron emission tomography scan in the diagnosis and follow-up of aortitis of
      the thoracic aorta.
AB  - We report a case of a 62-year-old female patient with an inflammatory reaction of
      the thoracic aortic wall. The diagnosis was made by computed tomographic (CT)
      scan, magnetic resonance imaging (MRI) and positron emission tomographic scan
      with 18-fluorodeoxyglucose (FDG-PET). The patient was treated with
      corticosteroids. The inflammatory parameters as well as FDG-uptake on PET scan
      returned to normal. Due to its aspecific presentation, the diagnosis of aortitis
      is often hard to establish. With this case the possible role of FDG-PET scan as a
      valuable tool in the diagnosis and monitoring of this inflammatory aortic
      disorder was demonstrated.

PMID- 10902047
TI  - Echocardiographic diagnosis of platypnoea-orthodeoxia syndrome after blunt chest
      trauma.
AB  - Platypnea-orthodeoxia syndrome is a rare entity most often related to an
      interatrial right-to-left shunt. We report the case of a patient who developed
      platypnoea-orthodeoxia shortly after a blunt chest wall trauma. Definite
      diagnosis was obtained with transoesophageal echocardiography using contrast in
      upright and recumbent position. A Medline search did not reveal any other case
      report of the syndrome after chest wall injury.

PMID- 10902048
TI  - The ratio of older women to men: historical perspectives and cross-national
      comparisons.
AB  - In nearly all populations throughout the world there are substantially more older
      women than men. Although there are many biological explanations for why women
      have greater longevity than men, the higher proportion of women in the older
      population appears to be a phenomenon of the twentieth century. Using
      contemporary data on population size and life expectancy in a large number of
      countries and historical life table data from a diverse subset of countries,
      cross-national contrasts and historical trends in the female to male ratio are
      explored. In the 1990's, only 4 countries had fewer women than men in the age
      group 75 years and older. The number of women per 100 men aged 75+ in the
      remainder of the world's countries ranged from 100 to 355. In general, countries
      with a lower overall life expectancy had a lower number of women per 100 men aged
      75+, while countries with higher overall life expectancy had a higher female to
      male ratio in this age group. A hundred years ago there were nearly equal numbers
      of women and men aged 75+ in many countries. In all countries studied, the female
      to male ratio increased as the century progressed. Historical life table data
      were used to calculate the probability of surviving through 5 stages of life:
      ages 0 to 5, 5 to 15, 15 to 40, 40 to 65, and 65 to 85. Although the probability
      of survival through all age intervals increased dramatically during the century,
      the current disparity in the size of the older populations of men and women can
      be explained primarily by the divergence in male and female probabilities of
      survival for the two older age intervals as the century progressed. Thus, with
      higher life expectancy, whether it be comparing countries or over time within a
      country, the proportion of the older population that is female is greater.
      Changes in survival probability in middle and late life, rather than childhood
      and young adulthood, have been responsible for the increased number of women
      compared to men in the older population.

PMID- 10902050
TI  - The menopause transition and the aging process: a population perspective.
AB  - The menopause transition period, extending from active reproductive capacity with
      well-characterized hormone profiles through reproductive senescence, has been
      less well studied than any other period of the life span except extreme old age.
      Yet, for the gerontologist, this is an important period to understand for at
      least two reasons. First, during this period changes in the neuroendocrine system
      and ovary may provide a model for the study of other aging-related processes.
      Second, specific characteristics of this transitional period (including duration,
      intensity, and age at menopause) may be considered "aging", and influence short
      term health and quality-of-life status, as well as life expectancy. In addition
      to discussing the menopause transition in terms of age and culture, we include
      some of the theories and conceptual models that can influence the nature and
      interpretation of information from this time period, and its ultimate impact on
      health and health practice.

PMID- 10902049
TI  - Do men and women follow different trajectories to reach extreme longevity?
      Italian Multicenter Study on Centenarians (IMUSCE).
AB  - Gender accounts for important differences in the incidence and prevalence of a
      variety of age-related diseases. Considering people of far advanced age,
      demographic data document a clear-cut prevalence of females compared to males,
      suggesting that sex-specific mortality rates follow different trajectories during
      aging. In the present investigation, we report data from a nationwide study on
      Italian centenarians (a total of 1162 subjects), and from two studies on
      centenarians living in two distinct zones of Italy, i.e., the island of Sardinia
      (a total of 222 subjects) and the Mantova province (Northern Italy) (a total of
      43 subjects). The female/male ratio was about 2:1 in Sardinia, 4:1 in the whole
      of Italy, and about 7:1 in the Mantova province. Thus, a complex interaction of
      environmental, historical and genetic factors, differently characterizing the
      various parts of Italy, likely plays an important role in determining the gender
      specific probability of achieving longevity. Gender differences in the health
      status of centenarians are also reported, and an innovative score method to
      classify long-lived people in different health categories, according to clinical
      and functional parameters, is proposed. Our data indicate that not only is this
      selected group of people, as a whole, highly heterogeneous, but also that a
      marked gender difference exists, since male centenarians are less heterogeneous
      and more healthy than female centenarians. Immunological factors regarding the
      age-related increase in pro-inflammatory status, and the frequency of HLA
      ancestral haplotypes also show gender differences that likely contribute to the
      different strategies that men and women seem to follow to achieve longevity.
      Concerning the different impact of genetic factors on the probability of reaching
      the extreme limits of the human life-span, emerging evidence (regarding mtDNA
      haplogroups, Thyrosine Hydroxilase, and IL-6 genes) suggests that female
      longevity is less dependent on genetics than male longevity, and that female
      centenarians likely exploited a healthier life-style and more favorable
      environmental conditions, owing to gender-specific cultural and anthropological
      characteristics of the Italian society in the last 100 years.

PMID- 10902051
TI  - Epidemiology of major age-related diseases in women compared to men.
AB  - Many observations indicate that women have a longer life expectancy than men.
      Population-based studies report that mortality and morbidity are higher in men
      than in women. The gender difference is constant in cardiovascular disease,
      cancer and dementia, the more frequent diseases in industrialized countries;
      these chronic conditions strongly influence longevity and quality of life in old
      persons. Biological, behavioral and environmental factors emerge as major
      contributors to the difference in mortality, morbidity and case fatality.
      However, the causes of gender differences remain poorly understood.

PMID- 10902052
TI  - Gender differences in disability: evidence and underlying reasons.
AB  - Women have greater longevity than men and represent a larger proportion of the
      expanding older population. Several health, disease, behavioral and
      sociodemographic factors contribute to the higher prevalence of disability in
      women compared to men. This paper presents a review of methodologic and
      epidemiologic considerations important to our understanding the gender
      differences in the prevalence of disability, and discusses underlying causes for
      these differences. Compared to men, women have a longer duration of life lived
      with disability, in part due to higher prevalence of non-fatal chronic
      conditions, constitutional factors such as lower muscle strength and lower bone
      density, and higher rates of life-style factors such as sedentary behavior and
      obesity. Several of these factors are modifiable, and provide important targets
      for researchers, clinicians, and public health practitioners in their efforts to
      reduce the burden of disability in the older population.

PMID- 10902053
TI  - Preventive health care for older women: life-style recommendations and new
      directions.
AB  - One of the key paradoxes in gerontology is that, despite a higher longevity,
      aging women experience worse health and longer disability than men. However,
      there is growing evidence that changes in life-style, medical interventions and
      systematic screening for certain diseases may substantially reduce the excess
      risk of major chronic conditions and disability in aging women, and therefore
      improve the quality of their late life. The potentials and public health
      implications of prevention in older women have been recently emphasized, not only
      by the scientific literature, but also by the media. More and more women are
      turning to their primary care physicians or other health professionals to seek
      counselling and help on how to reduce the burden of chronic disease and
      disability in old age by quitting smoking, eating a healthy diet, increasing
      physical activity, and coping with stress. Hormone replacement therapy also has a
      central role in this action of prevention. To maximize compliance, women should
      be provided a few guidelines that are easy to understand, and can be followed
      without interfering too much with their daily life activities. This article
      reviews the current literature on prevention in older women to select preventive
      strategies that are based on robust scientific evidence. This list of guidelines
      should be considered as a starting point for all those who are in charge of
      caring for middle-aged and older women.

PMID- 10902054
TI  - Importance of generativity for healthy aging in older women.
AB  - This article reviewed increasing evidence that remaining physically, cognitively,
      or socially active confers health benefits by delaying or preventing the onset of
      disease and disability in older adults. The desire to be generative, or to make a
      difference, has long been considered an important developmental objective in
      later years in order to give meaning to one's life, and may provide the necessary
      impetus for older women to initiate and maintain health-promoting activities.
      Because the prevalence of disability is greatest in older women, it is critical
      to find ways to maximize their opportunities for generative activity to promote
      healthier life-styles. Unfortunately, those who stand to gain most from the
      promotion of generative roles face many limiting factors, including low
      education, financial dependence and poverty, primary care-taking
      responsibilities, social isolation, and low self-efficacy. These obstacles may be
      too difficult and pervasive for an individual to overcome by oneself. Rather,
      these challenges need to be addressed through progressive changes in social
      programs that acknowledge the contributions that older adults can make in later
      years. Decreasing the structural lag between current social and demographic
      realities of older women's roles with increasing age will become ever more
      critical as a growing proportion of older women and men transition from a job
      outside the home to retirement.

PMID- 10902055
TI  - Caregiving arrangements of older disabled women, caregiving preferences, and
      views on adequacy of care.
AB  - The role of women in caregiving to elderly people has focused primarily on their
      involvement as givers of care. In contrast, this article focuses on older women
      as recipients of caregiving. Data from the WHAS and the WHAS Caregiving Study are
      used to describe: the relationship of caregiving arrangements among moderately to
      severely disabled older women to sociodemographic, health and functional status;
      the characteristics of primary family caregivers and the assistance they provide;
      preferences for caregiving arrangements among both care recipients and
      caregivers; and views on adequacy of caregiving among older women cared for by
      family. Overall, about one quarter of these women had no caregiver, reflecting
      the inclusion in the WHAS of women with only moderate functional difficulty, but
      close to two-thirds relied on family members, and 15% on paid help only. Greater
      reliance on family was associated with being age 80 or older, black, and living
      with others. Women with poorer functioning--more ADL and IADL difficulties,
      difficulty taking medications without help, low cognitive functioning, not
      emotionally vital--also were significantly more likely to be cared for by family.
      Caregiving preferences varied among older women and their husband and daughter
      caregivers. Husbands consistently viewed in-home family help as the best
      caregiving arrangement regardless of levels of need. Older women and daughter
      caregivers both saw nursing homes as the best option for people with dementia and
      substantial care needs. One-quarter of elderly women chose in-home paid help as
      the best arrangement for meeting ADL/IADL needs. Older women generally held
      positive views of the assistance they received from family members. Younger women
      and lower income women were more likely to indicate they received less help than
      needed.

PMID- 10902056
TI  - Financing care for aging women in the U.S.: international perspectives.
AB  - The aging of the U.S. population presents challenges in financing care and
      meeting the health and long-term care needs of older Americans. Women, who
      constitute a majority of the older adult population and a disproportionate share
      of those with low incomes, chronic conditions and long-term care needs, have much
      at stake in the future direction of health programs for aging Americans. This
      paper examines the status of older women in 12 industrialized nations to assess
      how the U.S. compares to other countries in terms of its aging female population.
      We find that women across the 12 industrialized countries have a longer life
      expectancy than men at ages 65 and 80, underscoring the universality of aging as
      a "women's issue". With respect to age composition, the U.S. lags behind many
      industrialized nations in the share of its elderly female population; by 2030,
      the proportion of women aged 65 and older, and 80 and older, will be lower in the
      U.S. than in any of the industrialized nations compared in this paper. Against
      this backdrop, the paper examines the characteristics of older adult women in the
      U.S., considers the role of Medicare in meeting the needs of aging women, and
      identifies gaps in coverage, primarily prescription drug and long-term care, that
      disproportionately affect older women. The paper concludes by considering how
      other nations provide and finance prescription drug and long-term care services
      for older adults, suggesting useful models for the U.S. to consider as it
      struggles to meet the demands of its aging population.

PMID- 10902057
TI  - System for safeguarding research volunteers scrutinized.

PMID- 10902058
TI  - NCI announces plan to overhaul clinical-trials system.

PMID- 10902059
TI  - FDA approves antibody-directed cytotoxic agent for acute myeloid leukemia.

PMID- 10902060
TI  - NABP proposes national competence assessment for technicians.

PMID- 10902061
TI  - Pharmacy technicians represented on Utah state board, NABP task force.

PMID- 10902062
TI  - Maine law aims to control drug costs.

PMID- 10902063
TI  - Efforts under way to immunize nursing home residents.

PMID- 10902064
TI  - AJHP's clinical content.

PMID- 10902065
TI  - Potential interactions between alternative therapies and warfarin.
AB  - Potential and documented interactions between alternative therapy agents and
      warfarin are discussed. An estimated one third of adults in the United States use
      alternative therapies, including herbs. A major safety concern is potential
      interactions of alternative medicine products with prescription medications. This
      issue is especially important with respect to drugs with narrow therapeutic
      indexes, such as warfarin. Herbal products that may potentially increase the risk
      of bleeding or potentiate the effects of warfarin therapy include angelica root,
      arnica flower, anise, asafoetida, bogbean, borage seed oil, bromelain, capsicum,
      celery, chamomile, clove, fenugreek, feverfew, garlic, ginger ginkgo, horse
      chestnut, licorice root, lovage root, meadowsweet, onion, parsley, passionflower
      herb, poplar, quassia, red clover, rue, sweet clover, turmeric, and willow bark.
      Products that have been associated with documented reports of potential
      interactions with warfarin include coenzyme Q10, danshen, devil's claw, dong
      quai, ginseng, green tea, papain, and vitamin E. Interpretation of the available
      information on herb-warfarin interactions is difficult because nearly all of it
      is based on in vitro data, animal studies, or individual case reports. More study
      is needed to confirm and assess the clinical significance of these potential
      interactions. There is evidence that a wide range of alternative therapy products
      have the potential to interact with warfarin. Pharmacists and other health care
      professionals should question all patients about use of alternative therapies and
      report documented interactions to FDA's MedWatch program.

PMID- 10902066
TI  - Angiotensin II-receptor antagonists: an overview.
AB  - Angiotensin II (AT-II)-receptor antagonists are reviewed. Research focused on
      blocking the renin-angiotensin system (RAS) led to the discovery of angiotensin
      converting-enzyme (ACE) inhibitors, which are effective in the treatment of
      hypertension but are associated with a high frequency of cough and other adverse
      effects. AT-II-receptor antagonists were developed as agents that would more
      completely block the RAS and thus decrease the adverse effects seen with ACE
      inhibitors. AT-II-receptor antagonists include losartan, valsartan, irbesartan,
      candesartan, eprosartan, telmisartan, and tasosartan. Several clinical trials
      have demonstrated that AT-II-receptor antagonists are as effective as calcium
      channel blockers, beta-blockers, and ACE inhibitors in the treatment of
      hypertension and induce fewer adverse effects. The adverse effects of AT-II
      receptor antagonists--dizziness, headache, upper-respiratory-tract infection,
      cough, and gastrointestinal disturbances--occur at about the same rate as with
      placebo. [corrected]. All available AT-II-receptor antagonists seem to be equally
      effective in reducing both systolic and diastolic blood pressure, and they are
      comparable in cost. Currently, AT-II-receptor antagonists are used either as
      monotherapy in patients who cannot tolerate ACE inhibitors or in combination with
      other antihypertensive agents. Angiotensin II-receptor antagonists are well
      tolerated and are as effective as ACE inhibitors in decreasing blood pressure.

PMID- 10902067
TI  - Clinical response to unintended infusion of doxorubicin and vincristine over one
      instead of four days.

PMID- 10902068
TI  - ASHP guidelines on the pharmacist's role in home care. Developed through the ASHP
      Council on Professional Affairs with the assistance of the Executive Committee
      and Professional Practice Committee of the ASHP Section of Home Care
      Practitioners and approved by the ASHP Board of Directors on April 27, 2000.

PMID- 10902069
TI  - Predictive validity of pharmacoeconomic modeling.

PMID- 10902071
TI  - HON code of conduct for medical and health Web sites.

PMID- 10902070
TI  - The other pharmacists in the American Civil War.

PMID- 10902072
TI  - Lyme disease: introduction.

PMID- 10902073
TI  - Immediate perception is the measure of all things.

PMID- 10902074
TI  - Surface topography and enamel-resin interface of pit and fissure sealants
      following visible light and argon laser polymerization: an in vitro study.
AB  - This in vitro study compared the effects of visible light and argon laser
      polymerization of pit and fissure sealants on surface topography and the enamel
      sealant interface. Twenty caries-free human molars and premolars underwent soft
      tissue debridement and a fluoride-free prophylaxis. Fluoride-releasing sealant
      (UltraSeal XT Plus, South Jordan, UT 84095) was placed on the occlusal surfaces
      per the manufacturer's instructions, but underwent either visible-light
      polymerization for 30s (n = 10), or argon laser polymerization (0.231 J/cm2) for
      10s (n = 10). The sealed teeth were thermocycled (500 cycles, 5 degrees to 50
      degrees C) in artificial saliva. Surface morphology was evaluated by SEM. The
      teeth were sectioned for polarized light and SEM evaluation of the enamel-sealant
      interface, with two sections per tooth prepared for SEM. Phosphoric acid was used
      to unmask the enamel-sealant interface with one section; while the other section
      was not exposed to the phosphoric acid. Surface morphology of the sealant
      material was similar with both visible light and argon laser polymerization;
      however, there was a tendency for occasional areas of mild, focal cratering of
      the sealant surface with laser-curing. The junction between sealant and adjacent
      unsealed enamel was a relatively smooth transition without gaps, microspaces,
      crazing, exfoliative changes, or microfractures with both visible light and laser
      cured sealants. Acid treatment of the sections revealed resin tags which extended
      into the adjacent enamel for a considerable distance on SEM examination. The
      resin tas were similar in length and morphology with both visible light and argon
      laser curing. The enamel-sealant interface with visible light and laser curing
      showed intimate contact between the sealant and etched occlusal enamel with close
      apposition of the sealant. No microspaces were identified between the sealant and
      the occlusal enamel. An intact, interdigitating interface between a sealant and
      the adjacent etched enamel provides the first line of defense against a
      cariogenic challenge. Visible-light and argon laser curing allows for an intimate
      enamel-sealant interface without microspaces and protects sealed enamel from
      cariogenic challenges. The benefit of argon laser polymerization, fluoride
      release and mechanical protection of sealant material may provide improved caries
      resistance in sealed pits and fissures and adjacent nonsealed enamel surfaces.

PMID- 10902075
TI  - Self-etching adhesive system for resin bonding.

PMID- 10902076
TI  - Simplified resin-based composite sealant.

PMID- 10902077
TI  - A comparison of acidic dietary factors in children with and without dental
      erosion.
AB  - The results of the UK Child Dental Health Survey of 1993 indicated that dental
      erosion was a problem in children, with acidic dietary components thought to be
      the main etiological factor. The aim of this study was to compare, in the form of
      a case control study, the diets of children with dental erosion with those who
      were caries-active or caries-free. Structured dietary histories were taken from
      309 age and gender matched children to determine the type and frequency of intake
      of acidic foods and drinks, together with any drinking habits that prolonged
      exposure of the teeth to dietary acids. Results showed that the children with
      erosion drank acidic beverages significantly more frequently than children who
      either had caries or were caries-free. Children with erosion also drank milk or
      water significantly less often than the control groups, and were more likely to
      have a swishing or holding habit associated with drinking. Fruit and vinegar
      consumption was higher in the erosion group, as was the taking of vitamin C
      supplements. The results of this study suggest that the increased consumption of
      acidic foods and drinks, particularly when associated with a swishing or holding
      habit, may contribute to the development of erosion in some children. Dietary
      advice should emphasize the dangers of a highly acidic as well as that of a
      cariogenic diet.

PMID- 10902078
TI  - The effect of virtual reality during dental treatment on child anxiety and
      behavior.
AB  - Virtual reality, a three-dimensional computer generated world, has been shown to
      relax adults during dental treatment. The purpose of this study was to
      investigate the effect of virtual reality on the behavior and anxiety of children
      during dental treatment. The behavior, anxiety and heart rate of twenty-six
      children, ages five to seven years were evaluated for the first five minutes of
      two restorative treatment visits. Thirteen children viewed virtual reality at
      their first restorative visit and not the second, and thirteen children viewed
      virtual reality at the second restorative visit and not the first. Before and
      immediately following the restorative visits, each child was instructed to draw a
      human figure. The restorative appointments were video recorded and heart rate
      monitored. The drawings and videotapes were rated independently by two examiners.
      The Koppitz method of evaluating drawings was used to measure anxiety. The Frankl
      behavior rating scale was used to evaluate behavior. Differences (ANOVA) in
      behavior (p < or = 0.50) and anxiety (p < or = 0.65) were not significant. The
      overall pulse rate was significantly lower (ANOVA p < or = 0.001) when the child
      was wearing glasses and viewing virtual reality. In conclusion, virtual reality
      during dental treatment had no significant effect on the behavior or anxiety but
      significantly reduced the pulse.

PMID- 10902079
TI  - Implications of parental compliance on decision making in care provided using
      general anesthesia in a low-income population.
AB  - The purpose of this study was to determine the compliance of parents for bringing
      the child back to the dentist for follow up dental care to aid in the decision
      making for care provided to the children of low income families requiring general
      anesthesia. The dental records of 244 children of low-income families were
      examined. Forty-three percent of the patients did not return for follow-up dental
      care. Consideration should be given to modifying treatment plans to include full
      coverage restorations and possibly delaying treatment before the eruption of the
      primary second molars.

PMID- 10902080
TI  - Dental anxiety in adolescents with a history of childhood dental sedation.
AB  - The purpose of this study was to determine whether adolescents with a history of
      childhood dental treatment using sedation had a higher level of self-reported
      dental anxiety than adolescents without such a history. A group of 287
      adolescents were identified who had received dental treatment using an identical
      sedation regime during childhood (mean age 5.05 +/- 0.16 years). A cover letter
      and a modified Dental Anxiety Scale (DAS) were mailed to the parents of all
      subjects. Sixty-one subjects (n = 61, 21 males, 40 females, mean age = 14.79 +/-
      0.16 years) (+/- SE) completed and returned the form. Age matched control
      subjects (n = 38, 18 females, 20 males, mean age = 14.36 +/- 0.06 years) who had
      no history of sedation or general anesthesia for dental or medical procedures
      also completed the DAS. Using the Mann-Whitney U test, the DAS score for test
      subjects (13.49 +/- 0.76) was found to be significantly higher (p < 0.05) than
      the DAS score for control subjects (10.84 +/- 0.69).

PMID- 10902081
TI  - Fewer people are on welfare rolls: does that mean that more children will receive
      dental care?
AB  - The number of welfare cases has been halved during this latest period of
      financial improvement. Can children who are "no longer poor" get dental care? A
      review of the complex interplay between welfare, Medicaid and dental services is
      provided.

PMID- 10902082
TI  - And you thought the nation's economy was doing well--children remain in poverty:
      Part II.
AB  - In an extended period of favorable economic indicators, improvements in child,
      poverty have slowed. In the late 1990s, almost one in five children continues to
      live in poverty at progressively lower financial levels. In addition, despite
      government safety net programs, significant number of children lack adequate
      health insurance and needed dental care.

PMID- 10902083
TI  - Multiple taurodontism: report of case.

PMID- 10902085
TI  - Tension delivery from short fibers in long muscles.
AB  - Many of the muscles of larger mammals (including humans) feature fibers that
      terminate without direct tendinous insertion, so fibers in these muscles must
      deliver their tension into the muscle belly. This raises many important issues
      regarding the pathway of tension delivery from the sarcomere to the tendon and
      the role of series-fiber and connective tissue compliance in the properties of
      the tension delivered. These issues have potentially great implications for
      understanding motor control and for strategies for reanimation of inactive
      muscles.

PMID- 10902084
TI  - Effects of cancer therapy on dental and maxillofacial development in children:
      report of case.
AB  - Malignant lymphoma is one of the most common hematological diseases of children.
      The prognosis is fairly good with multimodal cancer therapy. We reported a boy
      with Burkitt's lymphoma in the nasal cavity who received chemotherapy and
      irradiation of the head and neck area at four years of age. During seven years of
      follow-up, we studied the developmental effects of cancer therapy, including
      general growth, maxillofacial bones, and dentition. Compared with boys of
      matching age, the development of his entire body and maxillofacial bones was
      delayed. In the irradiated areas, the roots of teeth were short or poorly
      developed and the root apices showed premature closure. After the patient was in
      remission from the tumor in his early childhood, the long-term effects of cancer
      therapy on dental and maxillofacial development are worth our further evaluation
      and follow-up.

PMID- 10902086
TI  - Coronary smooth muscle and endothelial adaptations to exercise training.
AB  - Exercise training produces complex changes in intrinsic control of coronary
      vascular resistance. In smooth muscle, adaptations that alter Ca2+ regulation
      seem central, including changes in the function of sarcolemmal K+ and L-type Ca2+
      channels and the sarcoplasmic reticulum. Exercise training also increases the
      ability of the endothelium to release vasoactive factors, with increased
      expression and activity of endothelial cell nitric oxide synthase playing a key
      role.

PMID- 10902087
TI  - Sustaining exercise participation through group cohesion.
AB  - The general hypothesis to be examined by this article is that increased group
      cohesion leads to an increase in adherence to an exercise program over time.
      Although preliminary research is promising, there is a need for further research
      aimed at examining the model of group development in exercise classes, the impact
      of group cohesion on both group and individual exercise behavior, and the
      measurement of group cohesion.

PMID- 10902088
TI  - Assembly of the cellular powerhouse: current issues in muscle mitochondrial
      biogenesis.
AB  - Mitochondrial biogenesis occurs in muscle in response to chronic exercise,
      resulting in fatigue resistance. The assembly of the organelle is initiated by
      contraction-induced signals, which lead to the transcriptional activation of
      nuclear genes. This is accompanied by alterations in mRNA stability, as well as
      increases in protein import and mitochondrial DNA copy number, leading to a
      greater muscle mitochondrial content.

PMID- 10902089
TI  - Prevention of falls and fall-related fractures through biomechanics.
AB  - Falls and fall-related injuries are a major health problem for elderly people.
      Biomechanical studies provide important insight into the cause of such events and
      reveal new techniques for preventing them. The topics reviewed in this article
      include balance recovery, safe landing responses, impact forces during falls, and
      fracture prevention through exercise programs, hip pads, and energy-absorbing
      floors.

PMID- 10902090
TI  - Muscle structure and function in chronic neurological disorders: the potential of
      exercise to improve activities of daily living.
AB  - Our knowledge of muscle function in chronic neurological disorders, the effects
      of exercise, and how the effects might translate into improvements in activities
      of daily living is very limited. By building a bridge between basic muscle
      physiology and clinical rehabilitation, our knowledge of the pathophysiological
      mechanisms underlying muscle dysfunction in people with chronic neurological
      disorders will increase. This will facilitate the design and subsequent
      evaluation of exercise programs for these people and improve our understanding of
      the effects of such interventions on performance of activities of daily living.

PMID- 10902091
TI  - Self-efficacy determinants and consequences of physical activity.
AB  - This review examines self-efficacy as a determinant of exercise adherence and as
      an outcome of physical activity. Additionally, studies that have either
      manipulated self-efficacy or employed efficacy-based interventions to enhance
      exercise participation are discussed. Finally, recommendations for future
      applications of social cognitive theory to the physical activity domain are made.

PMID- 10902092
TI  - Functional magnetic resonance imaging of muscle.
AB  - Muscle functional magnetic resonance imaging (MRI) is used to compare the
      relative involvement of different muscles recruited during exercise. The method
      relies on the activity-induced increase in the nuclear magnetic resonance
      transverse relaxation time (T2) of muscle water, which is caused by osmotically
      driven shifts of fluid into the myofibrillar space. In addition to imaging of
      whole muscle recruitment, muscle MRI may reveal changes in motor unit
      organization during disease.

PMID- 10902093
TI  - Challenges in measuring physical activity in women.
AB  - This article identifies challenges facing researchers when studying physical
      activity in women. The three issues include social and cultural differences
      influencing women's physical activity habits, measuring lifetime physical
      activity, and measuring moderate-intensity physical activity within the context
      of women's lives.

PMID- 10902094
TI  - The pharmacotherapy of target symptoms associated with autistic disorder and
      other pervasive developmental disorders.
AB  - Research into the pharmacotherapy of autistic disorder has steadily increased
      over the past two decades. Several psychoactive medications have shown efficacy
      for selected symptoms of autistic disorder and can be used to augment critical
      educational and behavioral interventions that are the mainstays of treatment. A
      comprehensive review of medication trials conducted in individuals with autistic
      disorder and other pervasive developmental disorders is presented. The typical
      antipsychotic haloperidol is the best-studied medication in autistic disorder but
      is associated with a high rate of dyskinesias. Investigations to date suggest
      that the atypical antipsychotics such as risperidone have efficacy for certain
      symptoms of autistic disorder and may be better tolerated than typical
      antipsychotics. Preliminary results from trials with serotonin-reuptake
      inhibitors are favorable, although efficacy has not been demonstrated in younger
      age groups. Recent controlled studies of nalfrexone suggest that the drug has
      minimal efficacy. In two small controlled investigations, clonidine was more
      effective than placebo for a variety of symptoms, including hyperactivity and
      irritability; in one of these studies, however, the majority of patients relapsed
      within several months. Psychostimulants reduced hyperactivity and irritability in
      one small double-blind crossover study in children with autistic disorder,
      although these agents are frequently reported to exacerbate irritability,
      insomnia, and aggression in clinical populations. Recent controlled trials of
      secretin have not shown efficacy compared to placebo. Several other medications,
      including buspirone, mood stabilizers, and beta-blockers, have produced symptom
      reduction in some open-label studies and may warrant controlled investigation.

PMID- 10902095
TI  - Immigration and mental health: Mexican Americans in the United States.
AB  - The Hispanic population in the United States continues to expand rapidly due
      primarily to a large flow of immigrants from Mexico. Historical observations of
      disadvantage in the immigrant population, when compared to the native population,
      had helped to shape prevailing theories on immigration and mental health.
      However, data emerging from new research on Mexican Americans have come to
      challenge the old idea that immigrants are necessarily disadvantaged. The goal of
      this article is to review these new studies critically, to draw conclusions
      concerning the relationship between immigration and psychopathology, and to offer
      potential explanations for the major findings. We review five recent large-scale
      studies that examined the prevalence of mental disorders among Mexican-born
      immigrants and U.S.-born Mexican Americans in the United States. Results of these
      studies are inconsistent with traditional tenets on the relationship among
      immigration, acculturation, and psychopathology. They show that Mexico-born
      immigrants, despite significant socioeconomic disadvantages, have better mental
      health profiles than do U.S.-born Mexican Americans. Possible explanations for
      the better mental health profile of Mexican immigrants include research artifacts
      such as selection bias, a protective effect of traditional family networks, and a
      lower set of expectations about what constitutes "success" in America. The
      elevated rates of psychopathology in U.S.-born Mexican Americans may be related
      to easier access to abused substances and an elevated frequency of substance
      abuse among the U.S.-born.

PMID- 10902096
TI  - Logical processing, affect, and delusional thought in schizophrenia.
AB  - Deficits of logical reasoning have long been considered a hallmark of
      schizophrenia and delusional disorders. We provide a more precise
      characterization of "logic" and, by extension, of "deficits in logical
      reasoning." A model is offered to categorize different forms of logical deficits.
      This model acknowledges not only problems with making inferences, which is how
      logic deficits are usually conceived, but also problems in the acquisition and
      evaluation of premises (i.e., filtering of "input"). Early (1940-1969) and modern
      (1970-present) literature on logical reasoning and schizophrenia is evaluated
      within the context of the presented model. We argue that, despite a substantial
      history of interest in the topic, research to date has been inconclusive on the
      fundamental question of whether patients with delusional ideation show
      abnormalities in logical reasoning. This may be due to heterogeneous definitions
      of "logic," variability in the composition of patient samples, and floor effects
      among the healthy controls. In spite of these difficulties, the available
      evidence suggests that deficits in logical reasoning are more likely to occur due
      to faulty assessment of premises than to a defect in the structure of inferences.
      Such deficits seem to be provoked (in healthy individuals) or exacerbated (in
      patients with schizophrenia) by emotional content. The hypothesis is offered that
      delusional ideation is primarily affect-driven, and that a mechanism present in
      healthy individuals when they are emotionally challenged may be inappropriately
      activated in patients who are delusional.

PMID- 10902097
TI  - SAMe (S-adenosylmethionine).

PMID- 10902098
TI  - Exploring a model to improve diversity among trainees in psychiatry.

PMID- 10902099
TI  - Workplace sexual harassment: incidence, legal analysis, and the role of the
      psychiatrist.

PMID- 10902100
TI  - Heart failure: challenges and outcomes. Introduction.

PMID- 10902101
TI  - Cellular events linked to cardiac remodeling in heart failure: targets for
      pharmacologic intervention.
AB  - Over the past decade, there has been a paradigm shift in the understanding of
      heart failure pathophysiology. Heart failure is no longer conceptualized as a
      hemodynamic disorder resulting from changes in renal and hormonal function.
      Rather, the syndrome of heart failure is more complex and is characterized by
      abnormal myocyte growth, proliferation of cells in the extracellular matrix, and
      myocyte cell loss (apoptosis)--all of which culminate in significant structural
      remodeling of the heart and loss of ventricular function. The loss of ventricle
      function is preceded by an initiating event such as myocardial infarction, which
      leads to changes in cell function, activation of specific neurohormones and
      peptides, which in turn are linked to the remodeling of the ventricle, and
      progression of heart failure. This article discusses how changes in myocyte and
      nonmyocyte structure may contribute to the progression of heart failure. Insight
      into these mechanisms will provide a better understanding of newer pharmacologic
      approaches in the treatment of heart failure.

PMID- 10902102
TI  - Heart failure with preserved LV function: pathophysiology, clinical presentation,
      treatment, and nursing implications.
AB  - The syndrome of congestive heart failure occurring secondary to diastolic
      dysfunction accounts for the major pathophysiologic mechanism in up to one-third
      of patients who present with dyspnea on exertion and pulmonary congestion.
      Diastolic dysfunction is characterized by an alteration in the normal diastolic
      pressure-volume relationship while systolic function may be normal. It is
      manifested by impairment in the left ventricle's ability to relax and fill
      completely during diastole at normal low ventricular pressures. This subset of
      heart failure is most commonly associated with concentric left ventricular
      hypertrophy and ischemic states. Symptom presentation is similar to that
      associated with systolic dysfunction as are rates of rehospitalization. Diagnosis
      is made based on data obtained from invasive and noninvasive procedures. Unlike
      in the setting of systolic dysfunction, however, there are no large-scale
      randomized clinical trials evaluating drug efficacy that could be used to guide
      treatment for the management of diastolic dysfunction. Treatment recommendations,
      therefore, are empiric. Identifying and aggressively treating potentially
      reversible causes is a priority. Many of the same drugs used in the management of
      heart failure associated with systolic dysfunction are also used in the setting
      of diastolic impairment; however, dosages and rationale for administration may
      differ. Nursing interventions too are similar. Monitoring response to
      medications, especially in the acute setting, and comprehensive patient education
      are paramount. Much is yet to be learned about the management of diastolic
      dysfunction.

PMID- 10902103
TI  - Sudden cardiac death in heart failure.
AB  - Chronic heart failure (HF) and sudden cardiac death (SCD) present two major
      public health problems. The risk of death ranges from 10% to 50% annually in
      patients with HF, depending on the severity of disease. Approximately 50% of
      these deaths are sudden and presumed to be caused by dysrhythmias. This article
      defines the population at risk for SCD, explains the methods used for risk
      stratification, reviews current research on the pathophysiology of ventricular
      dysrhythmias in HF, and discusses pertinent clinical trials of therapeutic
      interventions on SCD in HF. The article also explores the effect of SCD on the
      patient and family with respect to counseling and education, resuscitative
      issues, and advanced directives.

PMID- 10902104
TI  - Pharmacotherapy of systolic heart failure: a review of recent literature and
      practical applications.
AB  - Since the publication of the Agency for Health Care Policy and Research
      Guidelines for treatment of heart failure, a number of new agents have been
      investigated for this indication. beta-Blockers have now been shown to improve
      outcomes in mild to moderate heart failure when added to standard therapy.
      Angiotensin II receptor antagonists have also been investigated and show promise.
      In general, calcium channel blockers are second- or third-line agents in patients
      refractory to other therapy. Investigational agents including spironolactone may
      also hold promise for future therapy.

PMID- 10902105
TI  - Intermittent positive inotrope infusion in the management of end-stage, low
      output heart failure.
AB  - The US Food and Drug Administration (FDA) has approved the use of the parenteral
      positive inotropes (dobutamine and milrinone) for short-term treatment of
      patients with acute, decompensated heart failure (HF). Despite the limited
      approved indication, parenteral, positive inotropes have been used clinically for
      long-term therapy to support the circulation as a bridge to transplant among
      patients waiting for an organ donor. The increasing number of patients with HF
      who are ineligible for transplant and the inadequate supply of donor organs have
      generated interest in the use of intermittent, parenteral positive inotropes for
      palliative therapy in patients with end-stage HF. Efforts by some clinicians to
      provide optimal symptomatic relief while controlling health care costs have
      produced a number of HF clinics that provide intermittent, parenteral inotropic
      therapy as a component of HF therapy. This article reviews the evidence for and
      against intermittent infusion of these agents in the ongoing care of people with
      end-stage HF who are not candidates for transplant. The available evidence
      indicates that intermittent positive inotropic infusion is associated with fewer
      HF symptoms, increased functional status, reduced health care costs, but also
      with increased mortality.

PMID- 10902106
TI  - Heart Messages: a tailored message intervention for improving heart failure
      outcomes.
AB  - Heart failure is a major health problem in the United States leading to high
      rates of mortality and morbidity and impaired quality of life. Assisting patients
      to improve compliance with their self-care regimen, including medications,
      dietary sodium restrictions, and self-monitoring (daily weights, edema
      assessment), may improve these poor outcomes. This article describes the
      development and initial evaluation of Heart Messages, a theory-based, tailored
      message intervention to improve compliance with the self-care regimen recommended
      for patients with heart failure. The project involved four phases, each of which
      is described in this article. The Heart Messages tailored message intervention
      program is available in both printed and Web-based formats. In a pilot study and
      clinical evaluation project, the program was found to be useful for patient
      education and feasible for implementation. Larger randomized trials are now
      warranted to evaluate the effectiveness of the intervention in improving
      compliance with the self-care regimen and thereby improving outcomes among
      patients with heart failure.

PMID- 10902107
TI  - Effect of psychosocial factors on physiologic outcomes in patients with heart
      failure.
AB  - Despite advances in its treatment, the epidemic of heart failure continues
      unabated in the United States and is escalating worldwide. The extremely high
      morbidity and mortality seen with heart failure demand creative approaches to
      this problem. Attention to nontraditional risk factors for rehospitalization and
      mortality, in addition to traditional medical risk factors, may yield improved
      outcomes. Psychosocial factors, particularly lack of social support and
      depression, are associated with poorer outcomes in cardiac patients. However, few
      studies have been conducted among patients with heart failure. In this article,
      the evidence relating poor quality of life, social isolation and lack of
      emotional support, anxiety and depression, and morbidity and mortality in
      patients with heart failure is discussed. Also explored are possible mechanisms
      for the association between psychosocial variables and physical outcomes and
      related clinical and research implications.

PMID- 10902108
TI  - Outcome measurement: self-management in heart failure.
AB  - Improvement in heart failure outcomes depend on patients' abilities to care for
      themselves and manage aspects of their condition, and patient self-management has
      itself become an outcome to be measured. Some behaviors, such as diet and fluid
      restriction, are prescribed, and self-management is often equated with adherence
      to the treatment regimen. Self-management has also been defined as cognitive
      decision making in response to symptoms and conceptualized as a process with
      stages from novice to expert. Greater understanding and measurement of patient
      decision making and self-management expertise facilitates the development of
      effective interventions to improve patient outcomes.

PMID- 10902109
TI  - Alkali-metal ion/molecule association reactions and their applications to mass
      spectrometry
AB  - This review will be concerned primarily with thermal alkali-metal ion association
      reactions of the general type: A+ + M + N reversible (A + M)+ + N. Where A
      denotes a positively charged alkali metal ion, M is neutral species and N works
      as a third body. As indicated, most association reactions are reversible, and the
      A-M bond derives primarily from electrostatic forces whose energy (affinity) is
      typically 50 kcal/mol or less, often much less. The review includes reaction
      mechanism, instrumentation, and application to mass spectrometry, together with
      reaction rates and alkali ion affinities of the classified compounds.

PMID- 10902110
TI  - Mass spectrometry in combinatorial chemistry.
AB  - In the fast expanding field of combinatorial chemistry, profiling libraries has
      always been a matter of concern--as illustrated by the buoyant literature over
      the past seven years. Spectroscopic methods, including especially mass
      spectrometry and to a lesser extent IR and NMR, have been applied at different
      levels of combinatorial library synthesis: in the rehearsal phase to optimize the
      chemistry prior to library generation, to confirm library composition, and to
      characterize after screening each structure that exhibits positive response. Most
      of the efforts have been concentrated on library composition assessment. The
      difficulties of such analyses have evolved from the infancy of the combinatorial
      concept, where large mixtures were prepared, to the recent parallel syntheses of
      collections of discrete compounds. Whereas the complexity of the analyses has
      diminished, an increased degree of automation was simultaneously required to
      achieve efficient library component identification and quantification. In this
      respect, mass spectrometry has been found to be the method of choice, providing
      rapid, sensitive, and informative analyses, especially when coupled to
      chromatographic separation. Fully automated workstations able to cope with
      several hundreds of compounds per day have been designed. After a brief
      introduction to describe the combinatorial approach, library characterization
      will be discussed in detail, considering first the solution-based methodologies
      and secondly the support-bound material analyses.

PMID- 10902111
TI  - Embracing the new testing paradigm.

PMID- 10902112
TI  - On seat height--adjust the workstation, not the worker.

PMID- 10902113
TI  - Management. Part I: Is safety really the No. 1 priority?

PMID- 10902114
TI  - HazCom on the company Intranet.

PMID- 10902115
TI  - Displacement ventilation control of tobacco smoke.

PMID- 10902116
TI  - FAQs & fables about protective clothing.

PMID- 10902117
TI  - 2000 apparel update.

PMID- 10902118
TI  - Securing confined spaces.

PMID- 10902119
TI  - Basic ergonomics for hand tool users.

PMID- 10902120
TI  - A war on weight & vibration.

PMID- 10902121
TI  - Say, can you see?

PMID- 10902122
TI  - Workstation workout.

PMID- 10902123
TI  - Drug and alcohol testing. DOT's, Part 40: Implications for employers.

PMID- 10902124
TI  - Learning the language of LOTO.

PMID- 10902125
TI  - Assuring best practices.

PMID- 10902126
TI  - Safety on a homicide investigation.

PMID- 10902127
TI  - [Respiratory allergies].

PMID- 10902128
TI  - [Epidemiology of respiratory allergies: current data].
AB  - Respiratory allergic diseases include seasonal allergic rhinitis or hay fever,
      perennial allergic rhinitis and allergic asthma. Prevalence of asthma is
      difficult to assess through epidemiological questionnaires. In France hay fever
      roughly affects 6% of children and 18% of teenagers and nasal allergies, more
      than one fourth of young adults. Prevalence of asthma is equal to 10 to 15% in
      teenagers and 7 to 9% in young adults. Risk factors include genetic as well as
      environmental factors. The role of the former have been exemplified in family
      studies, especially twin studies, and surveys of inbred populations.
      Environmental factors can be allergic or non-allergic. The influence of
      allergenic exposure on sensitization, occurrence and severity of respiratory
      allergic disease is well documented. The triggering influence of non-allergenic
      factors on established allergic diseases is also clear. In contrast, their
      implication in allergic sensitization and occurrence of allergic diseases need to
      be clarified.

PMID- 10902129
TI  - [Air pollution and allergic asthma].
AB  - The prevalence of asthma and allergic diseases is increasing in all
      industrialized countries. Genetic and environmental factors, and their
      interactions, are responsible for this increasing prevalence. A certain number of
      genes are currently screened to determine their suspected role in the
      immunogenesis of asthma, but in themselves, they cannot explain the increasing
      prevalence of asthma observed over the last 20 years. Environmental factors
      appear to be the most plausible explanation. Among these factors, air pollution
      and changing lifestyle as well as lower resistance due to fewer infectious
      diseases during childhood may be the most important factors. Experimental studies
      have shown that some pollutants such as ozone or diesel exhaust particles can
      interact with allergens, amplifying allergic reactions. Epidemiological studies
      have provided contradictory results. Acutely high concentrations of different
      pollutants can induce transient respiratory symptoms in asthmatic subjects but
      the long-term effects of air pollution on the genesis of asthma are still quite
      unclear.

PMID- 10902130
TI  - [Respiratory allergies and household allergenic environment].
AB  - Based on immunoassay techniques used to identify and quantify major indoor
      allergens, epidemiological studies have demonstrated that level of exposure
      depends on the geographical situation (climate, urbanization) and that there is a
      relationship between exposure and sensitization of predisposed patients. Most of
      the major mite allergens are proteases. For mammals and cockroaches, the major
      allergens belong to the retinal protein binding group. Determination of the
      airborne characteristics of the major indoor allergens is helpful in better
      understanding the pathophysiology of asthma. In the future, more precise
      diagnosis and more efficient immunotherapy will be possible through the
      development of recombinant allergens. The efficacy of allergen avoidance in
      allergic asthma has been demonstrated in several studies. Thus the respective
      role of different household allergens should lead to improved diagnosis and
      treatment of allergic diseases.

PMID- 10902131
TI  - [Genetic factors involved in asthma and atopy. Studies in British families].
AB  - Both asthma and atopy run families indicating a strong genetic component. To
      investigate possible candidate gene regions, we have recruited 131 families
      without reference to atopy and asthma (random sample) and 60 extended families
      with two or more members affected by asthma (multiplex sample). Using both
      candidate and genome screen approaches, we have been able to provide evidence
      supporting the presence of candidate genes on chromosome 11q (E237G) and 12q but
      we have been unable to confirm reports of linkage and association for asthma on
      5q. Our experience to date suggests that larger numbers of families are needed to
      increase the confidence of gene localisation and there is a need to improve the
      phenotypic description of asthma. Finally, it is essential that claims for
      linkage or association are confirmed in different populations using the same
      markers.

PMID- 10902132
TI  - [Response to IgE].
AB  - Over the last three decades, a good deal of work has focused on the IgE response
      due to the implication of these antibodies in allergic diseases. IgE antibodies,
      mediators of immediate hypersensitivity reactions, bind to specific high or low
      affinity receptors which are distributed on cell surfaces throughout the
      organism. Activation of receptors contributes to the different aspects of
      allergic inflammation. Regulation of the IgE response is complex and involves
      different factors modulating isotype synthesis, low-affinity receptor FcERII:CD23
      and its soluble portion, and the Th1/Th2 balance. Allergic diseases are
      characterized by a dysregulated IgE response, probably related to an imbalance
      favoring Th2 leading to exaggerated reaction. The advent of anti-IgE treatments
      can be seen as a notable progress in the management of atopic diseases. Their
      contribution will depend on the exact role of the IgE response in inflammatory
      allergic reactions.

PMID- 10902133
TI  - [Role of eosinophils in asthma].
AB  - Eosinophils are the most characteristic inflammatory cells in the airway mucosa
      in asthma. Eosinophils release highly toxic products and cytokines which may
      influence the immune system, amplify the inflammatory response and participate in
      damaging and remodeling processes that occur in the airway mucosa. Eosinophilic
      inflammation in asthma is related to the blunted perception of
      bronchoconstriction. The magnitude of eosinophil influx and the degree of
      activation of these cells in the airway mucosa are related to the severity of
      asthma and appear to play a key role in some cases of asthma death. The number
      and activation of eosinophils in the airway mucosa are related to the magnitude
      of airway hyperresponsiveness to bradykinin but not to an agonist acting directly
      on smooth muscle such as methacholine. Inhaled corticosteroids reduce eosinophil
      inflammation in asthma whereas beta 2-agonists appear to increase the magnitude
      of eosinophilic inflammation induced by allergen exposure. The eosinophilic
      inflammation can be assessed by non-invasive methods using sputum analysis and,
      indirecly, by measuring the airway reactivity to bradykinin.

PMID- 10902134
TI  - [Allergologic diagnosis].
AB  - There are two phases in allergologic diagnosis of respiratory diseases related to
      immediate hypersensitivity reactions: establishment of the allergic origin of the
      symptoms and identification of the causal allergen or allergens. In addition to
      the basic information obtained from history taking and physical examination,
      prick tests provide an easy, rapid, and low cost means of correctly identifying
      specific allergens. Laboratory tests such as serum assay of specific IgE can be
      useful when history and prick tests provide conflicting information, in
      exceptional cases when prick tests cannot be performed, or when specific
      desensitization is indicated. IgE assay is however of little use if prick tests
      are negative or clinical history poorly suggestive. The role of screening for
      atopy using multiple-allergen prick tests which give a global positive or
      negative result is poorly defined. Screening tests would be interesting if
      symptoms suggest, among other hypotheses, an allergic disease, especially if
      prick tests cannot be performed rapidly. Other atopy tests, such as total serum
      IgE, have little use. Finally, specific provocation tests are rarely needed for
      routine allergologic diagnosis. They may be useful in complex clinical situations
      or in particular conditions such as occupational allergy.

PMID- 10902136
TI  - [Asthma and professional activity].
AB  - Occupational asthma is largely documented in the recent medical literature but
      proposed criteria for its definition remain somewhat ambiguous. The main
      objective of this discussion is to point out the difficulties raised by
      individual diagnosis and collective actions related to occupational asthma. The
      main problems are: 1. Ambiguous definitions of occupational asthma; 2.
      Insufficient understanding of the different circumstances of diagnosis; 3.
      Difficulty in objective characterization of etiological agents due to the
      limitations of diagnostic procedures and interactions between agents; 4. Impact
      of the social consequences of diagnosis for the patient; 5. Limitations of
      prevention in the workplace. The coordinated efforts of the French Society of
      Pneumology and the French Society of Occupational Medicine should help provide
      answers to these problems.

PMID- 10902135
TI  - [Asthma and the child below 5 years of age: diagnosis and treatment].
AB  - Asthma is the most frequent chronic disease in pediatrics and the increase in its
      prevalence is a major public health problem. Diagnosis may be difficult in the
      young child, symptomatology most often occurring following a viral infection. It
      is important not to ignore a foreign body in the airways or fibrocystic disease
      and asthma remains, particularly in infants, a diagnosis of elimination.
      Misdiagnosis or insufficient treatment of asthma may risk the development of
      irreversible histological lesions and also could compromise pulmonary growth and
      the child's lung reserve. Spacer devices and nebulisers enable inhaled therapy to
      be administered to very young children. The value of early diagnosis is to
      institute appropriate treatment notably in severe asthma with inhaled
      corticosteroid therapy, the aim being to reduce remodelling lesions of the
      airways. The minimal effective dose should be defined to minimalise side-effects.
      The treatment of asthma is not restricted to pharmacotherapy: attempts should be
      made to reduce intercurrent viral infections, domestic pollution (including
      smoking) and allergenic concentrations. However, as for all chronic diseases, the
      clinician will encounter poor compliance. The work of education and support of
      health professionals is fundamental to the management of asthma.

PMID- 10902137
TI  - [Natural history of atopy].
AB  - Atopy is defined by an individual propensity to develop IgE-dependent reactions
      against environmental allergens. It could be now defined by a propensity to
      develop a Th2 response against such allergens, which takes into account not only
      the IgE production but also the eosinophil activation and the pivotal role of T
      lymphocytes in this process. A number of factors are determinants of atopy: some
      of them precede birth, such as genetic factors and some peculiarities of the
      immune system during pregnancy, in relation to maternal atopy, to in utero
      allergen exposure or to pregnancy itself. After birth, car pollution could modify
      the response to allergens by enhancing the IgE production. Food habits, by
      favoring intake of omega-6 polyunsaturated fat acids contained in some vegetal
      fat instead of omega-3 polyunsaturated acids from fish, could facilitate IgE
      dependent sensitization. Viral infections could, depending on their nature and
      their circumstances of occurrence protect from atopy inversely induce some
      sensitizations. Finally the degree of exposure to allergens themselves is
      proportional to the probability of sensitization. Together, these determinants of
      atopy could account for the higher prevalence of atopy in developed countries.
      The clinical expression of atopy varies during life from atopic dermatitis to
      rhinitis and asthma. Infancy is the time for dermatitis and sensitization to food
      allergens. Sensitization to airborne allergens occurs thereafter. Asthma,
      sometimes introduced by one or several bronchiolitis episodes follows to
      dermatitis or can be associated to it. Rhinitis appears in children or young
      adults. Seasonal, it is due to pollens and is rarely associated with asthma. In
      contrast, perennial, it is due to indoor allergens and leads to bronchial
      hyperreactivity and asthma.

PMID- 10902139
TI  - [Asthma and aspirin intolerance].
AB  - Undesirable reactions to aspirin and other non-steroidal antiinflammatory drugs
      compose a diverse group of clinical manifestations with different pathogenic
      mechanisms. In this review we describe one particular type of manifestation:
      aspirin-induced asthma. This syndrome describes a straightforward situation with
      typical clinical signs. The distinctive sign is asthma triggered by aspirin and
      NSAID. Data has accumulated over recent years concerning the interference of
      these drugs with arachidonic acid metabolism in the bronchi and lungs. In
      patients sensitive to aspirin inhibition of cyclooxygenase is accompanied by
      overproduction of cysteinyl leucotrienes. The clinical course of this condition,
      the pathogenic mechanisms of the undesirable reactions to aspirin, and treatment
      are discussed.

PMID- 10902138
TI  - [Does "intrinsic" asthma exist?].
AB  - Many asthmatics are not atopic. As compared to atopic ("extrinsic") asthma,
      nonatopic ("intrinsic") asthma occurs later in life, mostly in females, and nasal
      polyposis, aspirin sensitivity and corticodependence are common. In this patient
      population, there is no history of allergy, skin prick testing is negative for
      all aeroallergens tested and total as well as specific immunoglobulin E serum
      levels are within the normal range. Ten to forty percent of asthmatics are
      "intrinsic". It is important to define whether an asthmatic patient is atopic or
      not in order to recommend allergen avoidance in atopics. In the absence of
      allergy, it will be important to avoid bronchial irritants such tobacco, and in
      some patients aspirin and non steroidal anti-inflammatory agents. We will review
      recent findings obtained in a well defined population of atopic and nonatopic
      asthmatics. Analysis of bronchial mucosal expression of "pro-eosinophilic" and
      "pro-atopic" markers [IL-3, -4, -5, -13, GM-CSF, RANTES, MCP-3, IgE and high
      affinity IgE receptor (Fc epsilon RI)] demonstrates that there were more
      similarities than differences in immunopathology between atopic and nonatopic
      asthma.

PMID- 10902140
TI  - [Allergic bronchopulmonary aspergillosis].
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is an immunologic bronchopulmonary
      inflammation due to an immune response of the lower respiratory tract against
      Aspergillus fumigatus. The major clinical features of ABPA include asthma,
      recurrent pulmonary infiltrates, immediate wheal and flare skin reactivity to A.
      fumigatus, elevated total serum IgE levels, detectable serum precipitating
      antibodies to A. fumigatus, peripheral blood eosinophilia, elevated levels of
      Aspergillus-specific serum IgE and central bronchiectasis with normal distal
      structures. The diagnosis of ABPA should be considered in asthmatics of all ages.
      Evolution of the disease comprises five stages from the acute to the fibrotic
      stage including pulmonary fibrosis and respiratory insufficiency. The goals of
      ABPA treatment are to control patient's asthma and prevent exacerbations of ABPA.
      During the acute stage, prednisone should be administered. Antifungals agents
      (itraconazole) may be useful to prevent exacerbations of the disease.

PMID- 10902141
TI  - [Respiratory manifestations of anaphylactic shock].
AB  - Anaphylactic shock is the most dramatic expression of allergic manifestations.
      Respiratory involvement, whether expressed as edema of the upper airways, acute
      bronchospasm, or pulmonary edema, is the second most frequent manifestation of
      anaphylactic shock after cardiovascular events, and is in many cases life
      threatening. Respiratory signs of anaphylactic shock must be recognized rapidly
      to allow adequate treatment using epinephrine which has proven efficacy both in
      terms of symptom relief and prognosis.

PMID- 10902142
TI  - [Role of desensitization in the treatment of respiratory allergies].
AB  - Most authors consider immunotherapy as an efficient and safe treatment for pollen
      and mite allergic rhinitis. Recent meta-analyses showed that immunotherapy brings
      a significant benefit to some asthmatic patients depending on the type of
      allergen used, the severity of the disease, the number of allergenic
      sensitivities. Nevertheless everybody agrees that pharmacological treatment of
      asthma and immunotherapy must be complementary when indications of
      desensitization are given. All precautions to avoid adverse systemic effects or
      to cure them immediately must be taken. More work is needed as concerning the
      duration of the treatment, the efficacy of some local allergen administrations,
      the indications in the young child. The future is based on the use of antigenic
      peptides and of recombinant allergens.

PMID- 10902143
TI  - [Recombinant allergens: diagnostic use and therapeutic perspectives].
AB  - Techniques of genetic engineering applied to allergens have enabled the
      production of recombinant allergens. The validation of recombinant allergens
      implies that their immunological activity and their identity with natural
      allergens might be confirmed by in vitro and in vivo techniques carried out on a
      sufficiently large number of allergic subjects. Currently available results for
      the principal pneumoallergens are reported. Thus the work of validating
      recombinant allergen BeTv1 has been confirmed by in vitro tests and also by skin
      tests and nasal and bronchial provocation tests. The association of four
      recombinant allergens of phleole has enabled the detection in vitro of
      sensitisation to germinated pollens in 94.5% of patients. For mites the validity
      of group 2 recombinant allergens has been confirmed. A system enabling the
      expression of glycosylation of recombinant proteins was necessary to validate
      recombinant proteins in group 1 allergens. The recombinant allergen Blot5 is
      recognised as being effective in the detection of sensitization to Blomia
      tropicalis, a domestic allergen in sub tropical countries. The recombinant
      allergens Bla g 4 and Bla g 5 have been tested in vitro and in vivo and reactions
      were positive in nearly 50% of subjects sensitive to cockroaches. The recombinant
      Asp f 1 has been tested in subjects suffering from allergic bronchopulmonary
      aspergillosis and is positive in 60-85% of cases. Some studies are available for
      recombinant allergens of certain animal antigens (Equ c 1, Bos d 2). The
      consequences of clarifying recombinant allergens are then analysed: obtaining
      better standardised allergens for diagnostic tests, studying the spectrum of
      specificities of IgE induced by an allergen, the quantification of specific IgE,
      a better approach to mixed allergies with the help of recombinant allergens of
      the principal mixed allergens. Some recent progress has led to the production of
      modified recombinant allergens: the synthesis of recombinant polypeptides
      corresponding to T epitopes, the production of isoform recombinant allergens with
      reduced allergenic activity, the production of recombinant allergens of modified
      allergenic molecules by directed mutations and the production of recombinant
      fragments of allergenic molecules. The use of modified recombinant allergens is a
      way of permitting research which would, in the future, lead to new modalities of
      specific immunotherapy.

PMID- 10902144
TI  - [The problem mare part 2: treatment].
AB  - In this article different possible treatments for problem mares are discussed.
      The therapeutic possibilities vary and can be classified into anatomical
      correction, anti-infectious therapy, and treatment to enhance the uterine defence
      mechanisms. Anatomical correction and treatment with antibiotics are valuable
      therapies and have been used for many years. In recent years, stimulation of the
      mechanical defence mechanism of the uterus, by flushing it with physiological
      solution combined with parenteral oxytocin, has been shown to increase the chance
      of getting problem mares in foal.

PMID- 10902145
TI  - [Predecessors: veterinarians from earlier times (39). John Gamgee (1831-1894)].

PMID- 10902147
TI  - [Introduction by Secretary Brinkhorst of Agriculture, Food and Fisheries. 'To a
      ministry for food and greenness'].

PMID- 10902146
TI  - [Laparoscopic positioning and attachment of stomach displacement to the left in
      the cow].

PMID- 10902148
TI  - [Sifting out the IBR situation takes a lot of time. Beginning in   summer,
      hopefully more clarity].

PMID- 10902149
TI  - [In Process Citation]

PMID- 10902151
TI  - Protein evolution and structural genomics

PMID- 10902150
TI  - [Ten years of antibiotic policy for the Dutch veterinarian. What needs to be
      changed?].

PMID- 10902152
TI  - Enzyme evolution explained (sort of).
AB  - Sites in proteins evolve at markedly different rates; some are highly conserved,
      others change rapidly. We have developed a maximum likelihood method to identify
      regions of a protein that evolve rapidly or slowly relative to the remaining
      structure. We also show that solvent accessibility and distance from the
      catalytic site are major determinants of evolutionary rate in eubacterial
      isocitrate dehydrogenases. These two variables account for most of the rate
      heterogeneity not ascribable to stochastic effects.

PMID- 10902153
TI  - Modeling evolution at the protein level using an adjustable amino acid fitness
      model.
AB  - An adjustable fitness model for amino acid site substitutions is investigated.
      This model, a generalization of previously developed evolutionary models, has
      several distinguishing characteristics: it separately accounts for the processes
      of mutation and substitution, allows for heterogeneity among substitution rates
      and among evolutionary constraints, and does not make any prior assumptions about
      which sites or characteristics of proteins are important to molecular evolution.
      While the model has fewer adjustable parameters than the general reversible mtREV
      model, when optimized it outperforms mtREV in likelihood analysis on protein
      coding mitochondrial genes. In addition, the optimized fitness parameters of the
      model show correspondence to some biophysical characteristics of amino acids.

PMID- 10902154
TI  - Protein folds in the worm genome.
AB  - We survey the protein folds in the worm genome, using pairwise and multiple
      sequence comparison methods (i.e. FASTA and PSI-blast). Overall, we find that
      approximately 250 folds match approximately 8000 domains in approximately 4500
      ORFs, about 32 matches per fold involving a quarter of the total worm ORFs. We
      compare the folds in the worm genome to those in other model organisms, in
      particular yeast and E. coli, and find that the worm shares more folds with the
      phylogenetically closer yeast than with E. coli. There appear to be 36 folds
      unique to the worm compared to these two model organisms, and many of these are
      obviously implicated in aspects of multicellularity. The most common fold in the
      worm genome is the immunoglobulin fold, and many of the common folds are repeated
      in various combinations and permutations in multidomain proteins. In addition, an
      approach is presented for the identification of "sure" and "marginal" membrane
      proteins. When applied to the worm genome, this reveals a much greater relative
      prevalence of proteins with seven transmembrane helices in comparison to the
      other completely sequenced genomes, which are not of metazoans. Combining these
      analyses with some other simple filters allows one to identify ORFs that
      potentially code for soluble proteins of unknown fold, which may be promising
      targets for experimental investigation in structural genomics. A regularly
      updated worm fold analysis will be available from
      bioinfo.mbb.yale.edu/genome/worm.

PMID- 10902155
TI  - Sensitive sequence comparison as protein function predictor.
AB  - Protein function assignments based on postulated homology as recognized by high
      sequence similarity are used routinely in genome analysis. Improvements in
      sensitivity of sequence comparison algorithms got to the point, that proteins
      with previously undetectable sequence similarity, such as for instance 10-15% of
      identical residues, sometimes can be classified as similar. What is the relation
      between such proteins? Is it possible that they are homologous? What is the
      practical significance of detecting such similarities? A simplified analysis of
      the relation between sequence similarity and function similarity is presented
      here for the well-characterized proteins from the E. coli genome. Using a simple
      measure of functional similarity based on E.C. classification of enzymes, it is
      shown that it correlates well with sequence similarity measured by statistical
      significance of the alignment score. Proteins, similar by this standard, even in
      cases of low sequence identity, have a much larger chance of having similar
      function than the randomly chosen protein pairs. Interesting exceptions to these
      rules are discussed.

PMID- 10902156
TI  - High-throughput functional annotation of novel gene products using document
      clustering.
AB  - Gene products differentially expressed in healthy vs. diseased tissues may be
      considered drug targets since the change in their expression level can be related
      to the cause and progression of the disease studied. A significant portion of the
      proteins produced by these genes will be unknown and consequently their function
      must be characterised. The experimental elucidation of biochemical function must
      be supported by computational tools which can help predicting the possible
      function of a given protein from its amino acid sequence. We have designed a high
      throughput system which automatically analyses amino acid sequences deduced from
      differentially represented cDNA clones. The system attempts to assign a
      biological function to protein sequences by carrying out searches in sequence
      databanks and by locating functionally relevant motifs in the query sequences.
      The results delivered by the various prediction methods consist of the
      annotations of matching sequences and/or motifs, which are free-format texts
      written by humans and therefore may describe the same concept with synonymous
      words. It is desirable to present the results in such a way that the annotations
      describing the same biological function are grouped together. To this end we
      devised an algorithm that enables the hierarchical clustering of free-format
      documents based on their contents. The system is capable of detecting and
      flagging conflicting annotations, and will speed up the interpretation of the
      function prediction results.

PMID- 10902157
TI  - The evolution of duplicated genes considering protein stability constraints.
AB  - We model the evolution of duplicated genes by assuming that the gene's protein
      message, if transcribed and translated, must form a stable, folded structure. We
      observe the change in protein structure over time in an evolving population of
      lattice model proteins. We find that selection of stable proteins conserves the
      original structure if the structure is highly designable, that is, if a large
      fraction of all foldable sequences form that structure. This effect implies the
      relative number of pseudogenes can be less than previously predicted with neutral
      evolution models. The data also suggests a reason for lower than expected ratios
      of non-synonymous to synonymous substitutions in pseudogenes.

PMID- 10902159
TI  - Protein structure prediction in biology and medicine
AB  - Protein structure prediction from sequence has made rapid advances in the last
      few years, gaining increased attention after the success of the CASP meetings.
      Specifically, threading predictions were shown to work for many cases previously
      thought to be outside of the scope of prediction methods. The papers in this
      session address a wide scope of topics, ranging from techniques for validation of
      prediction methods and further improvements of threading algorithms, to specific
      applications of protein structure predictions in biology.

PMID- 10902158
TI  - Relating physicochemical properties of amino acids to variable nucleotide
      substitution patterns among sites.
AB  - Markov-process models of codon substitution were implemented that account for
      features of DNA sequence evolution (such as transition/transversion bias and
      codon usage bias) as well as heterogeneity of amino acid substitution pattern
      over sites. The codon (amino acid) sites are assumed to come from several classes
      (such as secondary structure categories), among which the rate of amino acid
      substitution and the effect of amino acid chemical properties vary. Parameters
      are estimated by the maximum likelihood method, which accounts for the
      phylogenetic relationship among species and corrects for multiple hits at the
      same site. The likelihood ratio test is used to compare models. Mitochondrial
      cytochrome b genes of 28 primate species are analyzed. The site-heterogeneity
      models provide much better fit to previous homogeneous models.

PMID- 10902160
TI  - Algorithmic approach to quantifying the hydrophobic force contribution in protein
      folding.
AB  - Though the electrostatic, ionic, van der Waals, Lennard-Jones, hydrogen bonding,
      and other forces play an important role in the energy function minimized at a
      protein's native state, it is widely believed that the hydrophobic force is the
      dominant term in protein folding. Here we attempt to quantify the extent to which
      the hydrophobic force determines the positions of the backbone alpha-carbon atoms
      in PDB data, by applying Monte-Carlo and genetic algorithms to determine the
      predicted conformation with minimum energy, where only the hydrophobic force is
      considered (i.e. Dill's HP-model, and refinements using Woese's polar
      requirement). This is done by computing the root mean square deviation between
      the normalized distance matrix D = (di,j) (di,j is normalized Euclidean distance
      between residues ri and rj) for PDB data with that obtained from the output of
      our algorithms. Our program was run on the database of ancient conserved regions
      drawn from GenBank 101 generously supplied by W. Gilbert's lab, as well as medium
      sized proteins (E. Coli RecA, 2reb, Erythrocruorin, 1eca, and Actinidin 2act).
      The root mean square deviation (RMSD) between distance matrices derived from the
      PDB data and from our program output is quite small, and by comparison with RMSD
      between PDB data and random coils, allows a quantification of the hydrophobic
      force contribution. A preliminary version of this paper appeared at GCB'99
      (http:?bibiserv.techfak.uni-bielefeld.de/gcb9 9/).

PMID- 10902161
TI  - Eliminating superfluous neighbor pairs while threading fold models.
AB  - In this paper we address the problem of identifying which of various possible
      spatial residue-residue neighbor pairs are plausible physical contacts without
      reference to the native structure side chain geometry. We propose an algorithm
      that eliminates most of the implausible physical contacts from the fold models.
      This algorithm exploits the correlations between the amino acid side chain
      rotamers and the direction of the physical contacts between the amino acid side
      chains. We use this algorithm to "filter" the score of the sequence-to-structure
      alignment. Filtering is dynamic, in the sense that the set of neighbor pairs
      contributing to the alignment score varies during threading. Whether or not a
      neighbor pair contributes to the score depends on the threaded amino acids. This
      score filtering improves the accuracy of the predicted sequence-to-structure
      alignment.

PMID- 10902162
TI  - Hybrid fold recognition: combining sequence derived properties with evolutionary
      information.
AB  - Recent assessments of structure prediction have demonstrated that (i) although
      fold recognition methods can often identify remote similarities when standard
      sequence search methods fail, the score of the top-ranking fold is not always
      significant enough to allow a confident prediction; (ii) the use of structural
      information such as secondary structure increases recognition accuracy; (iii)
      modern sequence-based methods incorporating evolutionary information from
      neighboring sequences can often identify very remote similarities; (iv) there is
      no one single method that is superior to other methods when evaluated over a wide
      range of targets, and (v) extensive human-expert intervention is usually required
      for the most difficult prediction targets. Here, I describe a new, hybrid fold
      recognition method that incorporates structural and evolutionary information into
      a single fully automated method. This work is a first attempt towards the
      automation of some of the processes that are often applied by human predictors.
      The method is tested with two cases that are often applied by human predictors.
      The method is tested with two fold-recognition benchmarks demonstrating a
      superior performance. The higher sensitivity and selectivity enable the
      applicability of this method at genomic scales.

PMID- 10902163
TI  - Folding nuclei in 3D protein structures.
AB  - This paper presents and analyzes the results of several new approaches to the
      problem of finding the folding nucleus in a given 3D protein structure. Firstly,
      we show that the participation of residues in the hydrophobic core and the
      secondary structure of native protein has a rather modest correlation with the
      experimentally found phi values characterizing the participation of residues in
      the folding nuclei. Then we tried to find the nuclei as the free energy saddle
      points on the network of the folding/unfolding pathways using the branch-and
      bound technique and dynamic programming. We also attempted to estimate the phi
      values from solving of kinetic equations for the network of protein
      folding/unfolding pathways. These approaches give a better correlation with
      experiment, and the estimated folding time is consistent with the experimentally
      observed rapid folding of small proteins.

PMID- 10902164
TI  - How universal are fold recognition parameters. A comprehensive study of alignment
      and scoring function parameters influence on recognition of distant folds.
AB  - A choice of sequence-structure similarity scoring function parameters can
      significantly alter results of the performance of the recognition of distantly
      related folds. It therefore constitutes a critical part of fold recognition
      process. In order to increase an understanding of the influence of parameter
      choice, a comprehensive benchmark of very hard (SFOLD) and medium hard (SFAM)
      fold recognition examples has been derived from the SCOP database of protein
      structure families. These benchmarks have subsequently been used to optimize,
      validate and analyze dependence of recognition sensitivity on alignment and fold
      similarity score parameters for different scoring functions. Significant
      variation of the common parameters has been observed for different functions,
      leading to the conclusion that optimal parameter sets are not universal. The
      scope of solutions common to any pair of scoring function is relatively small,
      hence, using jury method for fold prediction seems not appropriate. Also, using a
      redundant version of fold libraries significantly increases odds of
      identification of distantly related fold.

PMID- 10902165
TI  - Pinpointing the putative heparin/sialic acid-binding residues in the 'sushi'
      domain 7 of factor H: a molecular modeling study.
AB  - Factor H, a secretory glycoprotein comprising 20 short consensus repeat (SCR) or
      'sushi' domains of about 60 amino acids each, is a regulator of the complement
      system. The complement-regulatory functions of factor H are targeted by its
      binding to polyanions such as heparin/sialic acid, involving SCRs 7 and 20.
      Recently, the SCR 7 heparin-binding site was shown to be co-localized with the
      Streptococcus Group A M protein binding site on factor H (T.K. Blackmore et al.,
      Infect. Immun. 66, 1427 (1998)). Using sequence analysis of all heparin-binding
      domains of factor H and its closest homologues, molecular modeling of SCRs 6 and
      7, and surface electrostatic potential studies, the residues implicated in
      heparin/sialic acid binding to SCR 7 have been localized to four regions of
      sequence space containing stretches of basic as well as histidine residues. The
      heparin-binding site is spatially compact and lies near the interface between
      SCRs 6 and 7, with residues in the interdomain linker playing a significant role.

PMID- 10902166
TI  - Recognition of protein structure: determining the relative energetic
      contributions of beta-strands, alpha-helices and loops.
AB  - We examine the role of residues of secondary structure in recognition of the
      native structure of proteins. The accuracy of recognition was estimated by
      computing the Z-score values for fragments of protein chains in threading tests.
      By testing different combinations of secondary structure fragments of 240 non
      homologous proteins we show that the overwhelming majority of proteins can be
      successfully recognized by the energies of interaction between residues of
      secondary structure. We also found that beta-structures contribute more
      significantly to fold recognition than alpha-helices or loops. To validate the Z
      score calculations in measuring the accuracy of recognition we evaluated the
      deviation of the energy distribution from the normal law. The normal law
      satisfactory approximates the shape of the energy distribution for the majority
      of proteins and chain fragments; however, deviations are often observed for short
      fragments and for fragments with relatively high Z-score values. The results of
      the study justify recognition of remote homologs by threading methods based on a
      backbone of secondary structure rather than of a whole chain because loops of
      homologs differ more significantly than strands and helices, and the contribution
      of loops in structure recognition is relatively small.

PMID- 10902167
TI  - Probing structure-function relationships of the DNA polymerase alpha-associated
      zinc-finger protein using computational approaches.
AB  - We present the application of a method for protein structure prediction to aid
      the determination of structure-function relationships by experiment. The
      structure prediction method was rigourously tested by making blind predictions at
      the third meeting on the Critical Assessment of Protein Structure methods
      (CASP3). The method is a combined hierarchical approach involving exhaustive
      enumeration of all possible folds of a small protein sequence on a tetrahedral
      lattice. A set of filters, primarily in the form of discriminatory functions, are
      applied to these conformations. As the filters are applied, greater detail is
      added to the models resulting in a handful of all-atom "final" conformations.
      Encouraged by the results at CASP3, we used our approach to help solve a
      practical biological problem: the prediction of the structure and function of the
      67-residue C-terminal zinc-finger region of the DNA polymerase alpha-associated
      zinc-finger (PAZ) protein. We discuss how the prediction points to a novel
      function relative to the sequence homologs, in conjunction with evidence from
      experiment, and how the predicted structure is guiding further experimental
      studies. This work represents a move from the theoretical realm to actual
      application of structure prediction methods for gaining unique insight to guide
      experimental biologists.

PMID- 10902169
TI  - Molecules to maps: tools for visualization and interaction in computational
      biology

PMID- 10902168
TI  - Flexibility and critical hydrogen bonds in cytochrome c.
AB  - We show that protein flexibility can be characterized using graph theory, from a
      single protein conformation. Covalent and hydrogen bonds are modeled by distance
      and angular constraints, and a map is constructed of the regions in this network
      that are flexible or rigid, based on whether their dihedral bonds remain
      rotatable or are locked by other interactions in the network. This analysis takes
      only a second on a typical PC, and interatomic potentials; the most time
      consuming aspect of molecular dynamics calculations, are not required. Our
      preliminary work has shown that this approach identifies the experimentally
      observed, biologically important flexible regions in HIV protease and lysine
      arginine-ornithine binding protein. Here we analyze three evolutionarily distant
      cytochromes c, and find strong similarity between their flexible regions, despite
      having only 39% sequence identity. Furthermore, we show how the structural
      flexibility increases as the weaker hydrogen bonds are removed, as would happen
      under thermal denaturation of the protein. This approach identifies the critical
      hydrogen bonds that cross-link the tertiary structure.

PMID- 10902170
TI  - MappetShow: non-linear visualization for genome data.
AB  - The genome mapping projects now produce very dense maps with up to several
      thousands of markers per chromosome. Besides synteny plays a increasing role in
      mapping: enrichment of poor maps from the maps of close genomes (in terms of
      evolution) is a high-reward task. We propose a map viewer adapted to this
      situation: MappetShow gives a clear view of very dense maps and compares
      efficiently several maps. MappetShow is based on non-linear viewing and is
      written in Java. A map description language isolates the software from the data
      sources. This software was easily used on data coming from as different sources
      as an Object Request Broker, an Object-Oriented Database, or a flat data stream.
      MappetShow can be browsed at the URL http:?www.infobiogen.fr/services/Mappet.
      More generally we discuss how to use the non-linear viewing concept in molecular
      biology data visualization.

PMID- 10902171
TI  - ProFeel: low cost visual-haptic perceptualization of protein structure-structure
      alignments.
AB  - We describe ProFeel, an application for exploring molecular data from protein
      structure-structure alignments using a force-feedback joystick. Protein structure
      analysis is a useful application for multimodal information perceptualization
      because researchers in this area typically use several independent measures in
      assessment. A system that allows the user to simultaneously evaluate different
      criteria would therefore be quite useful. Four variables are assigned three
      different haptic effects each to allow the user to discern twelve separate data
      values. The haptic representation is coupled with a traditional molecular
      graphics visual display.

PMID- 10902172
TI  - Integrated tools for structural and sequence alignment and analysis.
AB  - We have developed new computational methods for displaying and analyzing members
      of protein superfamilies. These methods (MinRMS, AlignPlot and MSFviewer)
      integrate sequence and structural information and are implemented as separate but
      cooperating programs to our Chimera molecular modeling system. Integration of
      multiple sequence alignment information and three-dimensional structural
      representations enable researchers to generate hypotheses about the sequence
      structure relationship. Structural superpositions can be generated and easily
      tuned to identify similarities around important characteristics such as active
      sites or ligand binding sites. Information related to the release of Chimera,
      MinRMS, AlignPlot and MSFviewer can be obtained at
      http:?www.cgl.ucsf.edu/chimera.

PMID- 10902173
TI  - InVEST: interactive and visual edge selection tool for constructing evolutionary
      trees.
AB  - InVEST is an interactive and visual tool for constructing evolutionary trees from
      an ordered list of edges. In this paper it is shown that many methods for
      constructing evolutionary trees reduce to the edge selection problem.
      Furthermore, through a simulation study, it is shown that noninteractive methods
      for edge selection often perform poorly and can conceal alternative solutions.
      InVEST allows the user to interact with and explore an ordered list of edges
      facilitating the incorporation of user domain knowledge into the evolutionary
      tree construction process.

PMID- 10902174
TI  - The Ensemble/Legacy Chimera extension: standardized user and programmer interface
      to molecular Ensemble data and Legacy modeling programs.
AB  - Ensemble/Legacy is a toolkit extension of the Object Technology Framework (OTF)
      that exposes an object oriented interface for accessing and manipulating
      ensembles (collections of molecular conformations that share a common chemical
      topology) and driving Legacy programs (such as MSMS, AMBER, X-PLOR,
      CORMA/MARDIGRAS, Dials and Windows, and CURVES). Ensemble/Legacy provides a
      natural programming interface for running Legacy programs on ensembles of
      molecules and accessing the resulting data. Using the OTF reduces the time cost
      of developing a new library to store and manipulate molecular data and also
      allows Ensemble/Legacy to integrate into the Chimera visualization program. The
      extension to Chimera exposes the Legacy functionality using a graphical user
      interface that greatly simplifies the process of modeling and analyzing
      conformational ensembles. Furthermore, all the C++ functionality of the
      Ensemble/Legacy toolkit is "wrapped" for use in the Python programming language.
      More detailed documentation on using Ensemble/Legacy is available online
      (http:?picasso.nmr.ucsf.edu/dek/ensemble. html).

PMID- 10902175
TI  - Generating interactive molecular documentaries using a library of graphical
      actions.
AB  - Paper-based publishing of scientific articles limits the types of presentations
      that can be used. The emergence of electronic publishing has created
      opportunities to increase the range of formats available for conveying scientific
      content. We introduce the Graphical Explanation Markup Language, GEML,
      implemented as an XML format for defining molecular documentaries which exploit
      the interactive capabilities of electronic publishing. GEML builds upon existing
      molecular structure definitions such as the Protein Data Bank (PDB) standard file
      format. GEML provides a library of gestures (or actions) commonly used for
      structural explanations, and is extensible. XML allows us to separate explicit
      statements about how to highlight a molecular structure from the implementation
      of these instructions. We also present GEIS (Generator of Explanatory Interactive
      Systems), a program that takes as input a GEML documentary definition file and
      produces all the files necessary for an interactive, web-based molecular
      documentary. To demonstrate GEML and GEIS, we constructed a documentary capturing
      the difficult 3D notions expressed in two selected published reports about human
      topoisomerase I. We have created a prototype Java application, GEMLBuilder, as an
      editor of GEML files.

PMID- 10902177
TI  - Molecular network modeling and data analysis

PMID- 10902176
TI  - Visual management of large scale data mining projects.
AB  - This paper describes a unified framework for visualizing the preparations for,
      and results of, hundreds of machine learning experiments. These experiments were
      designed to improve the accuracy of enzyme functional predictions from sequence,
      and in many cases were successful. Our system provides graphical user interfaces
      for defining and exploring training datasets and various representational
      alternatives, for inspecting the hypotheses induced by various types of learning
      algorithms, for visualizing the global results, and for inspecting in detail
      results for specific training sets (functions) and examples (proteins). The
      visualization tools serve as a navigational aid through a large amount of
      sequence data and induced knowledge. They provided significant help in
      understanding both the significance and the underlying biological explanations of
      our successes and failures. Using these visualizations it was possible to
      efficiently identify weaknesses of the modular sequence representations and
      induction algorithms which suggest better learning strategies. The context in
      which our data mining visualization toolkit was developed was the problem of
      accurately predicting enzyme function from protein sequence data. Previous work
      demonstrated that approximately 6% of enzyme protein sequences are likely to be
      assigned incorrect functions on the basis of sequence similarity alone. In order
      to test the hypothesis that more detailed sequence analysis using machine
      learning techniques and modular domain representations could address many of
      these failures, we designed a series of more than 250 experiments using
      information-theoretic decision tree induction and naive Bayesian learning on
      local sequence domain representations of problematic enzyme function classes. In
      more than half of these cases, our methods were able to perfectly discriminate
      among various possible functions of similar sequences. We developed and tested
      our visualization techniques on this application.

PMID- 10902178
TI  - Algorithms for inferring qualitative models of biological networks.
AB  - Modeling genetic networks and metabolic networks is an important topic in
      bioinformatics. We propose a qualitative network model which is a combination of
      the Boolean network and qualitative reasoning, where qualitative reasoning is a
      kind of reasoning method well-studied in Artificial Intelligence. We also present
      algorithms for inferring qualitative networks from time series data and an
      algorithm for inferring S-systems (synergistic and saturable systems) from time
      series data, where S-systems are based on a particular kind of nonlinear
      differential equation and have been applied to the analysis of various biological
      systems.

PMID- 10902179
TI  - Discovery of regulatory interactions through perturbation: inference and
      experimental design.
AB  - We present two methods to be used interactively to infer a genetic network from
      gene expression measurements. The predictor method determines the set of Boolean
      networks consistent with an observed set of steady-state gene expression
      profiles, each generated from a different perturbation to the genetic network.
      The chooser method uses an entropy-based approach to propose an additional
      perturbation experiment to discriminate among the set of hypothetical networks
      determined by the predictor. These methods may be used iteratively and
      interactively to successively refine the genetic network: at each iteration, the
      perturbation selected by the chooser is experimentally performed to generate a
      new gene expression profile, and the predictor is used to derive a refined set of
      hypothetical gene networks using the cumulative expression data. Performance of
      the predictor and chooser is evaluated on simulated networks with varying number
      of genes and number of interactions per gene.

PMID- 10902180
TI  - Construction of a generalized simulator for multi-cellular organisms and its
      application to SMAD signal transduction.
AB  - In this paper, we report development of a generalized simulation system based on
      ordinary differential equations for multi-cellular organisms, and results of the
      analysis on a Smad signal transduction cascade. The simulator implements intra
      cellular and extra-cellular molecular processes, such as protein diffusion,
      ligand-receptor reaction, biochemical reaction, and gene expression. It simulates
      the spatio-temporal patterning in various biological phenomena for the single and
      multi-cellular organisms. In order to demonstrate the usefulness of the
      simulator, we constructed a model of Drosophila's Smad signal transduction, which
      includes protein diffusion, biochemical reaction and gene expression. The results
      suggest that the presence of negative feedback mechanism in the Smad pathway
      functions to improve the frequency response of the cascade against changes in the
      signaling.

PMID- 10902181
TI  - Delta-Notch lateral inhibitory patterning in the emergence of ciliated cells in
      Xenopus: experimental observations and a gene network model.
AB  - In diverse vertebrate and invertebrate systems, lateral inhibition through the
      Delta-Notch signaling pathway can lead to cells in initially uniform epithelial
      tissues differentiating in "salt-and-pepper", regular spacing patterns. In this
      paper we examine lateral inhibition during the emergence of ciliated cells in
      Xenopus embryonic skin, using experimental manipulations of the Delta-Notch
      pathway and a connectionist gene-network model of the process. The results of our
      model are in agreement with previous models of regular patterning through lateral
      inhibition and reproduce the observations of our experimental assays. Moreover,
      the model provides an account for the variability of embryonic responses to the
      experimental assays, points to a component of lateral inhibition that may be the
      chief source of this variability, and suggests ways to control it. Our model
      could thus serve as a tool to generate predictions about this and other regular
      patterning systems governed by lateral inhibition.

PMID- 10902182
TI  - Hybrid Petri net representation of gene regulatory network.
AB  - It is important to provide a representation method of gene regulatory networks
      which realizes the intuitions of biologists while keeping the universality in its
      computational ability. In this paper, we propose a method to exploit hybrid Petri
      net (HPN) for representing gene regulatory networks. The HPN is an extension of
      Petri nets which have been used to represent many kinds of systems including
      stochastic ones in the field of computer sciences and engineerings. Since the HPN
      has continuous and discrete elements, it can easily handle biological factors
      such as protein and mRNA concentrations. We demonstrate that, by using HPNs, it
      is possible to translate biological facts into HPNs in a natural manner. It
      should be also emphasized that a hierarchical approach is taken for our
      construction of the genetic switch mechanism of lambda phage which is realized by
      using HPNs. This hierarchical approach with HPNs makes easier the arrangement of
      the components in the gene regulatory network based on the biological facts and
      provides us a prospective view of the network. We also show some computational
      results of the protein dynamics of the lambda phage mechanism that is simulated
      and observed by implementing the HPN on a currently available tool.

PMID- 10902183
TI  - The effect of dynamic receptor clustering on the sensitivity of biochemical
      signaling.
AB  - Lateral clustering has emerged as a general mechanism used by many cellular
      receptors to control their responses to critical changes in the external
      environment. Here we derive a general mathematical framework to characterize the
      effect of receptor clustering on the sensitivity and dynamic range of biochemical
      signaling. In particular, we apply the theory to the bacterial chemosensory
      system and show that it can integrate a large body of experimental observations
      and provide a unified explanation to many aspects of chemotaxis. The principles
      of dynamic receptor clustering and signal amplification incorporated into this
      theory may underlie the design of many cellular networks.

PMID- 10902184
TI  - Data mining and knowledge discovery in molecular databases

PMID- 10902185
TI  - Mining the quantitative trait loci associated with oral glucose tolerance in the
      OLETF rat.
AB  - Although the synergetic effects of multiple marker loci regarding quantitative
      traits such as blood glucose level have attracted interest, previous conclusions
      have been based on assumptions that each marker locus behaves independently of
      the other, leading to approximation. To cope with this problem, this paper
      focuses on the effects of multiple genetic factors and tries to find significant
      marker combinations by using conjunctive rules regarding genotypes at multiple
      marker loci. Application of the proposed method on the OLETF model rat of non
      insulin dependent diabetes mellitus (NIDDM) has found significant combinations of
      marker loci with respect to oral glucose tolerance (OGT).

PMID- 10902186
TI  - Stochastic segment models of eukaryotic promoter regions.
AB  - We present a new statistical approach for eukaryotic polymerase II promoter
      recognition. We apply stochastic segment models in which each state represents a
      functional part of the promoter. The segments are trained in an unsupervised way.
      We compare segment models with three and five states with our previous system
      which modeled the promoters as a whole, i.e. as a single state. Results on the
      classification of a representative collection of human and D. melanogaster
      promoter and non-promoter sequences show great improvements. The practical
      importance is demonstrated on the mining of large contiguous sequences.

PMID- 10902187
TI  - Stochastic heuristic algorithms for target motif identification (extended
      abstract).
AB  - Target motifs are motifs that are "close" to one or more substrings in each
      sequence in one given set of sequences but are far from every substring in
      another given set of sequences. Target motifs have pharmaceutical applications;
      unfortunately, the problem of identifying target motifs is NP-hard and is thus
      unlikely to have efficient optimal solution algorithms. In this paper, we propose
      a set of simple modifications to the Gibbs Sampling heuristic for finding motifs
      which allows this heuristic to detect target motifs. We also present the results
      of several experiments relative to both simulated and real datasets which suggest
      that this modified heuristic is good at detecting target motifs under a variety
      of conditions.

PMID- 10902188
TI  - Identifying amino acid residues in medium resolution critical point graphs using
      instance based query generation.
AB  - Instance Based Query Generation is defined and applied to the problem of
      recognising amino acid residues in medium resolution critical point graphs. The
      technique is an amalgamation of Relational Instance Based Learning and Frequent
      Query Discovery in First Order Logic. Instances are automatically constructed
      from a deductive database and first order association rules are derived from the
      instances. The initial investigations presented here indicate that the technique
      is able to discriminate some of the larger amino acid types as well as
      discriminating the protein from background solvent. Identification of the smaller
      amino acids remains difficult and requires further work.

PMID- 10902189
TI  - Identification of coordinated gene expression and regulatory sequences

PMID- 10902190
TI  - Mutual information relevance networks: functional genomic clustering using
      pairwise entropy measurements.
AB  - Increasing numbers of methodologies are available to find functional genomic
      clusters in RNA expression data. We describe a technique that computes
      comprehensive pair-wise mutual information for all genes in such a data set. An
      association with a high mutual information means that one gene is non-randomly
      associated with another; we hypothesize this means the two are related
      biologically. By picking a threshold mutual information and using only
      associations at or above the threshold, we show how this technique was used on a
      public data set of 79 RNA expression measurements of 2,467 genes to construct 22
      clusters, or Relevance Networks. The biological significance of each Relevance
      Network is explained.

PMID- 10902191
TI  - EST databases as multi-conditional gene expression datasets.
AB  - Large-scale expression data, such as that generated by hybridization to
      microarrays, is potentially a rich source of information on gene function and
      regulation. By clustering genes according to their expression profiles, groups of
      genes involved in the same pathways or sharing common regulatory mechanisms may
      be identified. Publicly-available EST collections are a largely unexplored source
      of expression data. We previously used a sample of rice ESTs to generate 'digital
      expression profiles' by counting the frequency of tags for different genes
      sequenced from different cDNA libraries. A simple statistical test was used to
      associate genes or cDNA libraries having similar expression profiles. Here we
      further validate this approach using larger samples of ESTs from the UniGene
      projects (clustered human, mouse and rat ESTs). Our results show that genes
      clustered on the basis of expression profile may represent genes implicated in
      similar pathways or coding for different subunits of multi-component enzyme
      complexes. In addition we suggest that comparison of clusters from different
      species, may be useful for confirmation or prediction of orthologs.

PMID- 10902192
TI  - In silico analysis of gene expression patterns during early development of
      Xenopus laevis.
AB  - The information as to where and when a mRNA is present in a given cell is
      essential to bridge the gap between the DNA sequence of a gene and its
      physiological function. Therefore, a major component of functional genomics is to
      characterize the levels and the spatio-temporal domains of gene expression.
      Currently, there is just a few specialised public databases available storing the
      data on gene expression while they are needed as a resource for the field.
      Moreover, there is a need to develop and assess computational tools to compare
      and analyse expression profiles in a suitable way for biological interpretation.
      Here we describe our recent work on developing a database on gene expression for
      the frog Xenopus laevis, and on setting up and using new tools for the analysis
      and comparison of gene expression patterns. We used histogram clustering to
      compare expression profiles at both gene and tissue levels using a set of data
      coming from the characterization of the expression of genes during early
      development of Xenopus. This enabled us to draw a tree of tissue relatedness and
      to identify coexpressed genes by in silico analysis.

PMID- 10902193
TI  - Principal components analysis to summarize microarray experiments: application to
      sporulation time series.
AB  - A series of microarray experiments produces observations of differential
      expression for thousands of genes across multiple conditions. It is often not
      clear whether a set of experiments are measuring fundamentally different gene
      expression states or are measuring similar states created through different
      mechanisms. It is useful, therefore, to define a core set of independent features
      for the expression states that allow them to be compared directly. Principal
      components analysis (PCA) is a statistical technique for determining the key
      variables in a multidimensional data set that explain the differences in the
      observations, and can be used to simplify the analysis and visualization of
      multidimensional data sets. We show that application of PCA to expression data
      (where the experimental conditions are the variables, and the gene expression
      measurements are the observations) allows us to summarize the ways in which gene
      responses vary under different conditions. Examination of the components also
      provides insight into the underlying factors that are measured in the
      experiments. We applied PCA to the publicly released yeast sporulation data set
      (Chu et al. 1998). In that work, 7 different measurements of gene expression were
      made over time. PCA on the time-points suggests that much of the observed
      variability in the experiment can be summarized in just 2 components--i.e. 2
      variables capture most of the information. These components appear to represent
      (1) overall induction level and (2) change in induction level over time. We also
      examined the clusters proposed in the original paper, and show how they are
      manifested in principal component space. Our results are available on the
      internet at http:?www.smi.stanford.edu/project/helix/PCArray .

PMID- 10902194
TI  - ANN-Spec: a method for discovering transcription factor binding sites with
      improved specificity.
AB  - This work describes ANN-Spec, a machine learning algorithm and its application to
      discovering un-gapped patterns in DNA sequence. The approach makes use of an
      Artificial Neural Network and a Gibbs sampling method to define the Specificity
      of a DNA-binding protein. ANN-Spec searches for the parameters of a simple
      network (or weight matrix) that will maximize the specificity for binding
      sequences of a positive set compared to a background sequence set. Binding sites
      in the positive data set are found with the resulting weight matrix and these
      sites are then used to define a local multiple sequence alignment. Training
      complexity is O(lN) where l is the width of the pattern and N is the size of the
      positive training data. A quantitative comparison of ANN-Spec and a few related
      programs is presented. The comparison shows that ANN-Spec finds patterns of
      higher specificity when training with a background data set. The program and
      documentation are available from the authors for UNIX systems.

PMID- 10902195
TI  - Cluster, function and promoter: analysis of yeast expression array.
AB  - Gene clusters could be derived based on expression profiles, function
      categorization and promoter regions. To obtain thorough understanding of gene
      expression and regulation, the three aspects should be combined in an organic
      way. In this study, we explored the possible ways to analyze the large-scale gene
      expression data. Three approaches were used to analyze yeast temporal expression
      data: 1) start from clustering on the expression profiles followed by function
      categorization and promoter analysis, 2) start from function categorization
      followed by clustering on expression profiles and promoter analysis, and 3) start
      from clustering on the promoter region followed by clustering on expression
      profiles. For clustering analysis on the time-series data, we developed a largest
      first algorithm, which provide a mechanism for quality control on clusters. For
      promoter analysis, we developed a core-extension algorithm.

PMID- 10902196
TI  - Natural language processing for biology

PMID- 10902197
TI  - Knowledge representation and indexing using the unified medical language system.
AB  - Ontologies and semantic frameworks can be used to improve the accuracy and
      expressiveness of natural language processing for the purpose of extracting
      meaning from technical documents. This is especially true when a rich ontology
      such as the Unified Medical Language System (UMLS) is available. This paper
      reports on some tools being developed to make this possible and on some
      experience with a user interface based on ontologies and semantic networks that
      allows for interactive knowledge exploration.

PMID- 10902198
TI  - Two applications of information extraction to biological science journal
      articles: enzyme interactions and protein structures.
AB  - Information extraction technology, as defined and developed through the U.S.
      DARPA Message Understanding Conferences (MUCs), has proved successful at
      extracting information primarily from newswire texts and primarily in domains
      concerned with human activity. In this paper we consider the application of this
      technology to the extraction of information from scientific journal papers in the
      area of molecular biology. In particular, we describe how an information
      extraction system designed to participate in the MUC exercises has been modified
      for two bioinformatics applications: EMPathIE, concerned with enzyme and
      metabolic pathways; and PASTA, concerned with protein structure. Progress to date
      provides convincing grounds for believing that IE techniques will deliver novel
      and effective ways for scientists to make use of the core literature which
      defines their disciplines.

PMID- 10902200
TI  - Biobibliometrics: information retrieval and visualization from co-occurrences of
      gene names in Medline abstracts.
AB  - Successful information retrieval from biomedical literature databases is becoming
      increasingly difficult. We have developed a prototype system for retrieving and
      visualizing information from literature and genomic databases using gene names.
      The premise of our work is that, if two genes have a related biological function,
      the co-occurrence of two gene names (or aliases of those genes) within the
      biomedical literature is more likely. From a collection of Medline documents, we
      have extracted the number of co-occurrences of every pair of Saccharomyces
      cerevisiae genes. The query is automatically conflated to include gene aliases as
      well. In addition, the retrieved document set can be filtered by the user with a
      MeSH term. From this co-occurrence data we construct a matrix that contains
      dissimilarity measurements of every pair of genes, based on their joint and
      individual occurrence statistics. A graph is generated from this matrix, with
      node and edge inclusion being determined by a user-defined threshold. Nodes of
      the graph represent genes, while edge lengths are a function of the occurrence of
      the two genes within the literature. Nodes can be hypertext-linked to sequence
      databases, while edges are linked to those Medline documents that generated them.
      The system is a tool for efficiently exploring the biomedical information
      landscape and may act as a inference network.

PMID- 10902199
TI  - EDGAR: extraction of drugs, genes and relations from the biomedical literature.
AB  - EDGAR (Extraction of Drugs, Genes and Relations) is a natural language processing
      system that extracts information about drugs and genes relevant to cancer from
      the biomedical literature. This automatically extracted information has
      remarkable potential to facilitate computational analysis in the molecular
      biology of cancer, and the technology is straightforwardly generalizable to many
      areas of biomedicine. This paper reports on the mechanisms for automatically
      generating such assertions and on a simple application, conceptual clustering of
      documents. The system uses a stochastic part of speech tagger, generates an
      underspecified syntactic parse and then uses semantic and pragmatic information
      to construct its assertions. The system builds on two important existing
      resources: the MEDLINE database of biomedical citations and abstracts and the
      Unified Medical Language System, which provides syntactic and semantic
      information about the terms found in biomedical abstracts.

PMID- 10902202
TI  - Computer-aided combinatorial chemistry and cheminformatics

PMID- 10902201
TI  - Automatic extraction of protein interactions from scientific abstracts.
AB  - This paper motivates the use of Information Extraction (IE) for gathering data on
      protein interactions, describes the customization of an existing IE system, SRI's
      Highlight, for this task and presents the results of an experiment on unseen
      Medline abstracts which show that customization to a new domain can be fast,
      reliable and cost-effective.

PMID- 10902203
TI  - Compound acquisition strategies.
AB  - Compound acquisition has always been a very important component in the discovery
      and development of new biologically active entities. With the rapid advances in
      high throughput screening coupled with the ever-decreasing time requirements for
      the discovery phase, the number and quality of compounds screened is of great
      importance. This presentation will discuss some of the techniques and processes
      that can be used in compound acquisition.

PMID- 10902204
TI  - Searching for molecules with similar biological activity: analysis by fingerprint
      profiling.
AB  - We have recently developed a mini-fingerprint (MFP) representation for small
      molecules that performs well in database searches for compounds with similar
      biological activity. The MFP consists of only 54 bit positions that account for
      numerical ranges of three two-dimensional (2D) descriptors or the presence or
      absence of defined structural fragments. Here we present an analysis method,
      termed fingerprint profiling, to systematically compare bit patterns of compounds
      belonging to different biological activity classes. Some but not all bit
      positions were variably occupied in seven different activity classes and
      responsible for the detection of structure-activity differences. The analysis has
      made it possible to rank bit positions and encoded molecular descriptors
      according to their importance for our similarity search calculations. Fingerprint
      profiling can be applied to any keyed bit string representation and should be
      helpful, for example, to analyze descriptor distributions in large compound
      databases.

PMID- 10902205
TI  - Library design and virtual screening using multiple 4-point pharmacophore
      fingerprints.
AB  - The use of multiple potential 4-point three-dimensional (3-D) pharmacophores for
      the design of combinatorial libraries and for virtual screening is discussed.
      These 3-D pharmacophoric fingerprints can be calculated from both ligands and
      complementary to a protein site, with a common frame of reference, and can be
      very rapidly searched to identify common and different 4-point pharmacophoric
      shapes in compounds and protein sites. A new extension to the method for
      structure-based design is reported that uses the shape of the target site as an
      additional constraint. This enables the docking process, for example in library
      design and virtual screening, to be quantified in terms of how many, and which,
      pharmacophoric hypotheses can be matched by a compound or a library of compounds.

PMID- 10902206
TI  - PICCOLO: a tool for combinatorial library design via multicriterion optimization.
AB  - Combinatorial library design is by nature a multicriterion problem. These
      criteria often include reagent diversity, product similarity to lead compounds
      and product novelty with respect to a corporate compound bank. More recently,
      developability and druglikeness have also attracted much attention in library
      design practices. To address this multicriterion design problem, we have
      developed a computer program (PICCOLO) that simultaneously optimizes all the
      factors under consideration using a weighted sum optimization technique. In this
      paper, we describe the overall design of this program and the formulation of
      individual penalty functions that characterize the underlying design criteria. We
      also give an example to illustrate the process and the result of a library design
      using this program.

PMID- 10902207
TI  - Applications of information theory to biology

PMID- 10902208
TI  - Information dynamics of in vitro selection-amplification systems.
AB  - Selection-amplifications systems provide a means of engineering biomacromolecules
      with new properties. The combination of stringent functional selection with the
      ability to amplify single molecules confers great specificity on the evolving
      population. Yet such systems like many complicated chemical kinetic mechanisms
      can show a range of unstable and metastable behavior. These instabilities can be
      investigated using the Shannon entropy of the evolving population. It is shown
      that the Shannon entropy provides a Lyapounov function for exploring dynamic
      stability. A simple model of in vitro evolution is presented and stability
      conditions are established. It is seen that fairly simple directed evolution
      models can exhibit a range of dynamical behavior.

PMID- 10902209
TI  - Average mutual information of coding and noncoding DNA.
AB  - One basic problem in the analysis of DNA sequences is the recognition of protein
      coding genes. Computer algorithms to facilitate gene identification have become
      important as genome sequencing projects have turned from mapping to large-scale
      sequencing, resulting in an exponentially growing number of sequenced nucleotides
      that await their annotation. Many statistical patterns have been discovered that
      are different in coding and noncoding DNA, but most of them vary from species to
      species, and hence require prior training on organism-specific data sets. Here,
      we investigate if there exist species-independent statistical patterns that are
      different in coding and noncoding DNA. We introduce an information-theoretic
      quantity, the average mutual information (AMI), and we find that the probability
      distribution functions of the AMI are significantly different in coding and
      noncoding DNA, while they are almost identical for different species. This
      finding suggests that the AMI might be useful for the recognition of protein
      coding regions in genomes for which training sets do not exist.

PMID- 10902211
TI  - Human genome variation: analysis, management and application of SNP data

PMID- 10902210
TI  - Finite-temperature sequence alignment.
AB  - We develop a statistical theory of probabilistic sequence alignments derived from
      a 'thermodynamic' partition function at finite temperature. Such alignments are a
      generalization of those obtained from information-theoretic approaches. Finite
      temperature statistics can be used to characterize the significance of an
      alignment and the reliability of its single element pairs.

PMID- 10902212
TI  - ALFRED: a Web-accessible allele frequency database.
AB  - We present a Web-accessible database (ALFRED) that allows public access to gene
      frequency data for a diverse set of population samples and genetic systems. The
      data in ALFRED are modeled based on the experience and needs of a single
      laboratory, but with the expectation that the database will meet the needs of a
      much broader scientific community that needs population-specific gene frequency
      estimates. Our database currently contains data on more than 40 populations
      representing most major regions of the world and data on more than 150 genetic
      systems including SNPs, STRPs, and insertion-deletion polymorphisms. While data
      are not available for all population-genetic system combinations, over 2000
      allele frequency tables already exist. In this paper, we enumerate the broad
      needs in the scientific domain, describe their significance, and describe how we
      have designed the database to meet those needs. We compare our database with
      dbSNP, the NCBI database that has a broader but overlapping purpose.

PMID- 10902213
TI  - Linkage disequilibrium mapping using single nucleotide polymorphisms--which
      population?
AB  - There is considerable interest in the potential of single nucleotide
      polymorphisms (SNPs) for mapping complex traits which are determined by genes of
      small individual effect (oligogenes). It is thought likely that many oligogenes
      are themselves common polymorphisms, perhaps biallelic, for which there is
      effectively neutral selection reflected in late age of onset. The extent of
      detectable linkage disequilibrium between SNP x SNP pairs and SNP x oligogene
      pairs is of considerable interest, particularly in the context of identifying
      'favourable' populations. Unfortunately data are sparse and few populations have
      been extensively sampled. Polymorphisms with the appropriate characteristics that
      have been studied are blood groups in the Rhesus and MNS systems for which there
      are extensive data on four pairs of biallelics. These might be regarded as
      surrogates for SNP-SNP or SNP-oligogene pairs. By developing and applying an
      approach, previously used for major genes, to evaluate association (rho) in SNP
      haplotypes, it is evident that, with some exceptions, there is little difference
      between isolates and large populations. Furthermore it is apparent that there is
      useful linkage disequilibrium even for the MN-Ss locus pair (0.195 cM apart), in
      both large populations and isolates. This is somewhat more favourable to linkage
      disequilibrium mapping than a recent simulation suggests.

PMID- 10902214
TI  - An analytic solution to single nucleotide polymorphism error-detection rates in
      nuclear families: implications for study design.
AB  - Recently, there has been increased interest in using Single Nucleotide
      Polymorphisms (SNPs) as a method for detecting genes for complex traits. SNPs are
      diallelic markers that have the potential to be inexpensively produced using chip
      technology. It has been suggested that SNPs will be beneficial in study designs
      that utilize trio data (father, mother, child). In our previous work, we
      calculated the probability of detecting Mendelian errors at a SNP locus for a
      trio randomly selected from a population in Hardy-Weinberg equilibrium. The
      highest error-detection rate was 30%. Here we investigate the error-detection
      rate when additional sibs are genotyped. We define an error to be a change from a
      1 allele to a 2 allele, or vice versa. Typing one additional sib increases the
      detection rate on average by 10-13%. Typing two additional sibs increases the
      detection rate on average by 14-19%. The increase in the detection rate is
      dependent on the allele frequencies. Equal allele frequencies produce the lowest
      detection rates, independent of true error rates and number of offspring
      genotyped. Typing additional siblings not only improves error-detection rates,
      but can also provide additional linkage information. In order to increase linkage
      information and error-detection rates, at least two additional siblings should be
      ascertained when available.

PMID- 10902215
TI  - The haplotype linkage disequilibrium test for genome-wide screens: its power and
      study design.
AB  - The focus of human genetics continues to shift toward the dissection of complex
      phenotypes. Integral to these endeavors is the development of powerful analytical
      tools. To this end, we propose a novel method designated the haplotype linkage
      disequibrium (LD) test for identifying diseases genes. The basic structure of the
      haplotype test statistic is a chi-square in which haplotypes, as opposed to
      individual marker data, are compared between cases and controls. Specifically, we
      performed power calculations and demonstrate that the use of haplotypes improves
      the power of mapping disease genes. We show that this approach can be used for
      initial genome-wide screens in mapping disease genes. Furthermore, we
      investigated the factors influencing statistical power of the method and
      discussed basic principals underlying study design. Published data from the
      Hereditary Hemochromatosis region was used to illustrate the utility of the
      haplotype test. Also discussed is its relationship with linkage disequibrium.

PMID- 10902216
TI  - Distance education. Part 1. Conceptualization and development.
AB  - INTRODUCTION: The Graduate Diploma/Masters in Family Medicine were developed at
      Monash University as distance education courses from a previous on-campus version
      of a Masters course in response to real and perceived needs for more flexible
      forms of delivery. METHOD: Conceptualization and development involved
      consultation with experts in distance education and the application of adult
      learning principles, phenomenology and constructivism in course design.
      CONCLUSION: Despite initial difficulties and delays, course objectives were met
      through the application of standardised distance learning and teaching methods
      applied to four core and 15 clinical elective subjects. These were developed
      within a three year period for delivery in a predominantly paper based format.

PMID- 10902217
TI  - Distance education. Part 2. Student characteristics, program characteristics,
      administration and future direction.
AB  - INTRODUCTION: A descriptive analysis of student and program characteristics was
      undertaken. METHOD: Data were obtained using student enrollment forms, periodic
      surveys and regular feedback which formed part of the formative evaluation.
      RESULTS: In the five year period 1992-1996, 433 doctors enrolled in the Graduate
      Diploma, of which 56 proceeded onto Masters. Of the 433, 60% were male. The mean
      age of students was 41 years, with rural (49%) and solo (45%) practitioners over
      represented; 20% held the FRACGP and 15% resided outside Australia. Around 20%
      deferred or withdrew during the five year period. Of the 56 Masters enrollments,
      16 had completed the degree in minimum time, with a further 30 completing within
      two years. Reasons for enrollment were largely professional with many students
      expressing the need to overcome isolation and gain intellectual stimulation.
      CONCLUSION: This Diploma/Masters course which has a strong clinical component has
      attracted considerable interest among established general practitioners. The
      program appears to have succeeded because of its flexible delivery, lack of
      exclusive research orientation and its firm grounding in general practice.

PMID- 10902218
TI  - Distance education. Part 3. Assessment of and feedback to students at a distance.
AB  - INTRODUCTION: Assessment of students at distance, in a course with over 20 units
      (subjects), provides special challenges in providing timely, accurate and
      detailed feedback both formatively and summatively. METHOD: A description of
      assessment practices including reflective journals, essays, critical appraisal of
      literature, case studies or teaching presentations in video and written format,
      clinical audits, and large research projects is provided. The impact of a
      multitude of criterion-referenced methods of students, teachers and
      administrative services as well as quality assurance issues are measured.
      CONCLUSION: Students preferred multiple levels of formative and summative
      assessment using criterion referencing to exams. These methods were thought to be
      contextually relevant to clinical practice and examined knowledge, cognition and
      performance appropriately. Length of assessment task, difficulty with English as
      a second language and lack of detail or clarity on written feedback posed
      problems for a number of students. Quality assurance procedures have been put
      into place to rectify some of these problems.

PMID- 10902219
TI  - Distance education. Part 4. Supervision of family medicine research at a
      distance. A formative evaluation.
AB  - INTRODUCTION: A survey on supervision of research projects was undertaken among
      current general practitioner students, recent graduates and supervisors of a
      Masters of Family Medicine degree. The aim was to describe and compare the
      experience of the three groups and, in particular, to identify the problems
      associated with distance supervision. METHODS: A self-administered questionnaire
      survey was distributed to current students (n = 21), graduates (n = 16) and
      current supervisors (n = 7). RESULTS: Forty out of 44 doctors returned completed
      questionnaires. Distance was a relatively minor barrier to successful
      supervision, provided that the student and supervisor established good
      communication patterns and were able to respond to each other with minimal delay.
      The commencement of the study and its final write-up were critical phases in the
      supervision process. DISCUSSION: Communication, including emotional and
      psychological support, was at least as important as expert opinion in helping
      Masters students to successfully complete their research projects. Attention must
      be paid to establishing good understanding and regular means of communication at
      the beginning of the supervisory process.

PMID- 10902221
TI  - Distance education. Part 6. Evaluation of a core subject within the Graduate
      Diploma/Masters in Family Medicine. Principles of general practice.
AB  - AIM: To evaluate 'Principles of General Practice' (formerly known as the Academic
      Basis of General Practice), a core unit of the Graduate Diploma/Masters in Family
      Medicine. METHOD: Content analysis of feedback sheets and transcripts from
      teleconferences were analysed to facilitate the process evaluation of this core
      unit. Content analysis of qualitative responses to the question: 'What did you
      learn?' at the end of the course formed the impact evaluation. RESULTS: GPs who
      participated in the evaluation of the Principles of General Practice highlighted
      four learning outcomes in response to the question: 'What did you learn?'
      Categories included discipline specific and patient specific. Personal and
      professional outcomes were further divided into the following subcategories:
      affirmation of current practice; confidence in dealing with uncertainty; engaging
      in reflective practice; overcoming professional isolation; and providing
      opportunities for career change. CONCLUSIONS: The most cited reasons for
      participating in this course were the professional and personal. Students found
      that the course clarified their roles, raised self-esteem and confidence, and
      provided them with a sense of pride in their profession. The reflective learning
      style resulted in students gaining insight into themselves and their therapeutic
      roles, with reported changes in clinical practice, including more confidence in
      dealing with uncertainty. In addition to meeting course objectives there were a
      number of unanticipated outcomes identified. The most surprising was the
      recognition that general practice was a medical specialty, supported by a body of
      literature. For some, this assisted them to overcome feelings of professional
      isolation and alienation. A number of students saw this course as a stimulus to
      blending their clinical work with a teaching role to enhance professional growth
      and satisfaction.

PMID- 10902220
TI  - Distance education. Part 5. Family medicine research at a distance. Guidelines
      for supervisors.
AB  - INTRODUCTION: This paper recommends guidelines for the supervision of Masters
      degrees or similar postgraduate courses, in which research projects are
      supervised at a distance. METHODS: The guidelines are based on the experiences of
      the authors with a five year old Masters of Family Medicine degree and a
      formative evaluation conducted by questionnaire survey among its students,
      graduates and supervisors. RESULTS: It is important to establish ground rules for
      communication at an early point in the supervisory process. Supervisors need to
      take into account psychosocial, pedagogical and organisational aspects of their
      mentorship of students. DISCUSSION: These guidelines are relevant to courses
      where there remains a strong one-to-one relationship between supervisors and
      students. In these cases, 'distance' need not be a barrier provided that both
      sides are aware of and committed to maintaining good patterns of communications
      with each other.

PMID- 10902222
TI  - Distance education. Part 7. Evaluation of the Graduate Diploma of Family
      Medicine. Does a distance education course for GPs influence their reported
      clinical and professional practice?
AB  - INTRODUCTION: Course evaluation is essential for continuous enhancement of
      teaching. This evaluation aimed to assess the impact of the Graduate Diploma of
      Family Medicine on the clinical practices, community activities, learning styles
      and personal lives of its graduates. METHODS: Cross-sectional postal
      questionnaire survey of all 1993 to 1997 graduates of the Graduate Diploma in
      Family Medicine (n = 233). RESULTS: A response rate of 70% was achieved. Male
      respondents felt that they treated a greater variety of conditions (p = 0.04),
      had undertaken more procedural work (p = 0.03), and had increased procedural
      confidence (p = 0.009) compared to female respondents, while the female
      respondents referred more (p = 0.03). Solo practitioners tended to look for
      evidence in clinical decision making (p = 0.006) and applied critical appraisal
      techniques when reading medical information provided by pharmaceutical
      representatives (p = 0.04). Group practitioners tended to participate in more
      research projects (other than drug trials) than solo practitioners (p = 0.03).
      There was a difference between full and part time general practitioners, even
      after controlling for gender, with the former more certain that general practice
      is where they wanted to be (p = 0.005), they also felt more competent in
      interpreting data, e.g. ECGs (p = 0.013). More male students indicated they
      preferred a reflective learning style than females (p = 0.04). CONCLUSION: The
      clinical electives of the Graduate Diploma in Family Medicine had the most
      significant impact on the clinical practices of full time GPs who were
      predominantly male graduates. Gender differences were apparent in styles of
      practice as males tended to conduct more procedural work, while female graduates
      preferred the gatekeeper role and referred more. The course also impacted on the
      students' approach to evidence in their clinical decision making. They were more
      critical of medical information provided by pharmaceutical representatives who
      are one of the major sources of CME for many GPs. Future evaluations should be
      based on experimental and quasi-experimental designs in order to measure changes
      in student perceptions and clinical practice, as well as more objective measures
      of learning styles.

PMID- 10902223
TI  - Differences of disease characteristics between genders in emergency department
      elderly of a community hospital in Taiwan.
AB  - BACKGROUND: The purpose of this study was to catalog the chief complaints and
      diagnoses of elderly patients visiting to a Taiwanese emergency department (ED),
      and to compare gender differences. METHODS: ED computer log data of patients 65
      years and older, who visited the ED from July 1995 to June 1996, were
      retrospectively reviewed. The computer log data for each patient was entered
      prospectively by the doctor providing the ED care. All patient data were
      separated by gender, and then subdivided into trauma and non-trauma groups for
      analysis. RESULTS: There were 8038 elderly patients treated during the study
      period. The most common male chief complaint was dyspnea, and for females, it was
      abdominal pain, followed by injuries for both genders. Falls were the most common
      mechanism of injury for both genders, but they were more common among females
      (63.2% vs. 46.1%, p < 0.001). Motorbike accidents, however, were 3 times as
      frequent among males (16.05% vs. 5.45%, p < 0.001). Males presented most commonly
      with COPD (12.2%), compared to only 4.16% for females (p < 0.001), with urinary
      retention the second most common diagnosis (5.04% vs. 0.72%, p < 0.001). Females
      suffered a greater number of urinary tract infections (5.42% vs. 2.03%, p <
      0.001), presentations for renal failure (2.98% vs. 1.56% p < 0.001), and diabetes
      associated problems (4.58% vs. 2.48%, p < 0.001). CONCLUSION: Elderly females
      presented to the ED more frequently with urinary tract and diabetic problems;
      while their male counterparts presented with complications of COPD, urinary
      retention, and motorbike accidents.

PMID- 10902224
TI  - The effects of Tai Chi Chuan on postural stability in the elderly: preliminary
      report.
AB  - BACKGROUND: Tai chi chuan (TCC) is a traditional Chinese conditioning exercise,
      consisting of a series of graceful movements linked together in a continuous
      sequence so that the body is constantly shifting from one foot to the other. We
      propose that subjects practicing TCC will have better postural control and
      stability than will active non-practitioners. METHODS: We compare static and
      dynamic postural controls in 14 TCC practitioners and 14 healthy active older
      adults using the Smart Balance Master System. The TCC group, containing 7 male
      and 7 female subjects (mean age, 70.9 +/- 3.3 years), had been practicing TCC
      regularly for 2 to 35 years. The control group included 4 male and 10 female
      healthy and active older subjects (mean age, 69.1 +/- 3.1 years), with age and
      body size matched to the TCC group. RESULTS: The results of static postural
      control tests showed no differences between the TCC and control groups under
      simple conditions (eyes open, eyes closed, swaying vision, and eyes open with
      swaying surface), but in the more complicated conditions (eyes closed with sway
      referenced support and sway-referenced vision and support), the TCC group had
      significantly better results than the control group. In the dynamic balance test,
      the TCC group had significantly better results only in the rhythmic forward
      backward weight-shifting test. CONCLUSION: Our data demonstrate that regular TCC
      practitioners have better postural stability, especially in the more complicated
      conditions with disturbed visual and somatosensory conditions.

PMID- 10902225
TI  - Unexpected delivery before arrival at hospital: an observation of 18 cases.
AB  - BACKGROUND: We identify and discuss risk factors related to prolonged
      hospitalization, as compared with the average hospital stay (5.1 days) of normal
      delivery neonates throughout the last 10 years, associated with babies delivered
      unexpectedly in southern Taiwan. METHODS: This is a retrospective case series
      study; those babies delivered unexpectedly, including both pre-term and term
      infants, were pooled out from normal-birth babies, and their laboratory data and
      clinical histories were reviewed and discussed. RESULTS: There was a total of 18
      babies delivered unexpectedly during the past 10 years. Out of these 18 babies,
      there was only 1 mortality. The mean gestational age was 38 weeks; the mean birth
      body weight was 3097 g, and the average hospital stay was 6.2 days. Possible
      clinical factors related to prolonged hospitalization include the following:
      hypothermia, hypoglycemia, hyperkalemia, polycythemia, and a relatively high
      ratio of positive findings of chest X-ray study. CONCLUSION: The best way to
      reduce prolonged hospitalization caused by unexpected delivery is by prevention,
      or if this is not possible, by increasing the knowledge and effectiveness of
      handling intrapartum accidents. Hypothermia, hypoglycemia, hyperkalemia,
      polycythemia, and positive chest radiological results were the most common
      reasons for prolonged hospital stays in unexpectedly delivered neonates. However,
      due to the limited cases in our study, a larger group study is still needed in
      the future for more precise statistical information.

PMID- 10902226
TI  - Healing of untidy traumatic skin defect of the face by secondary intention.
AB  - BACKGROUND: Untidy facial skin defects manifest extensive soft tissue injury and
      contamination. Since modern surgical principles emphasize immediate wound
      closure, most surgeons should learn to convert an untidy wound to a tidy one and
      to reconstruct defects immediately if possible with the use of grafts and flaps.
      However, in some situations, healing by secondary intention remains advantageous.
      The purpose of this study is to reevaluate this traditional approach. METHODS:
      Twenty patients with untidy facial skin defects were treated conservatively over
      a 4-year period. The defects ranged from 2 x 2 cm2 to 6 x 4 cm2 in size. The
      depths of wounds were classified into partial-thickness in 9 patients, full
      thickness in 7 patients, and deep defects in 4 patients. Each patient was
      instructed on wound care, which included daily cleaning with normal saline,
      followed by application of hydrocolloid occlusive dressing. Prophylactic
      antibiotics were not used. RESULTS: The mean follow-up period was 17 months. All
      wounds healed within 3 to 5 weeks. There was no wound infection. One patient
      developed a hypertrophic scar over the cheek, and received excision of the scar
      and resurfacing with full-thickness skin graft. Two patients had residual
      traumatic tattooing which was resolved by laser therapy. Two patients had
      hypopigmentation/hyperpigmentation problems. Most patients (18/20) were satisfied
      with both functional and cosmetic results. CONCLUSION: Conservative wound care
      with hydrocolloid occlusive dressing allows good healing by secondary intention
      for traumatic facial defects in selected patients.

PMID- 10902227
TI  - Treatment refusal: analysis of 15 cases.
AB  - BACKGROUND: In this paper, we investigate the reasons for treatment refusal at
      Linkou and Kaohsiung Chang Gung Memorial Hospitals, and offer ways to improve the
      doctor-patient relationship. METHODS: Cases were collected during a 2-year period
      according to the criterion of notification of "refused treatment" on consultation
      sheets, with a total of 1631 consultation sheets. All cases were discussed once a
      week in detail by psychiatrists and the consulting medical staff, and were
      followed up from 1 to 4 weeks. All cases were treated by the processes of
      informed consent and crisis intervention. The final results for the reasons of
      treatment refusal and psychiatric diagnoses were made by psychiatrists and the
      consulting medical staff. RESULTS: The number of cases compatible with the
      criterion was 15 (10 men and 5 women). The reasons for treatment refusal included
      poor communication, inadequate information, lack of competency, denial and shock
      reaction, reappearance of the suffered experience, and autonomy of patients. The
      distribution of psychiatric diagnoses included 8 with major depressive disorders,
      2 with delirium, 1 with schizophrenic disorder, 1 with adjustment disorder, 1
      with acute stress disorder (post-traffic accident), 1 with alcohol dependence,
      and 1 was deferred. After adequate processes of informed consent and crisis
      intervention, 12 persons accepted medical treatment. CONCLUSION: We should give
      patients adequate informed consent and crisis intervention to establish a good
      doctor-patient relationship and to respect the patients' autonomy for their
      choice of treatment.

PMID- 10902228
TI  - Direct angioplasty of totally occluded left main coronary artery in acute
      myocardial infarction complicated by cardiogenic shock: report of two cases and
      literature review.
AB  - Acute total occlusion of the left main coronary artery is usually characterized
      by a rapid course of deterioration that challenges therapeutic intervention.
      Unlike subtotal occlusion of the left main coronary artery, acute total occlusion
      of the left main coronary artery is extremely rare and has a grave prognosis.
      Most patients with this problem die suddenly or go into cardiogenic shock. Direct
      percutaneous transluminal coronary angioplasty (PTCA) was performed on 2
      patients, both suffering from cardiogenic shock due to acute total occlusion of
      the left main coronary artery. Both patients underwent coronary artery bypass
      surgery subsequently. One patient, who had substantial intercoronary collaterals,
      remained asymptomatic at 31 months of follow-up. The other, who had no
      intercoronary collateral circulation, expired 3 days after coronary artery bypass
      surgery. We conclude that direct PTCA to the acutely occluded unprotected left
      main coronary artery in cardiogenic shock patients is a potentially life-saving
      procedure, and the presence or absence of collaterals from the dominant right
      coronary artery will influence the clinical outcome.

PMID- 10902229
TI  - Tuberculosis presenting with pelvic mass, peritoneal lesions, and elevation of
      serum CA125 mimicking malignant tumor: a case report.
AB  - Tuberculosis is a curable infective disease which can mimic a malignant tumor. We
      report on a young woman who presented with abdominal fullness, body weight loss,
      and microcytic anemia. A pelvic mass and peritoneal lesions were found. The serum
      CA125 level was high. The initial gynecologic echo and abdominal CT scan revealed
      bilateral ovarian mass with peritoneal lesions, and malignancy was highly
      suspected. Diagnostic laparoscopy was performed, and peritoneal tuberculosis was
      pathologically proven. Combination anti-tuberculosis therapy was prescribed for
      one year. She was followed up in the outpatient clinic regularly with symptom
      improvement, body weigh gain, and improvement of anemia. We suggest that in cases
      of a pelvic mass and peritoneal lesions, with elevation of the serum CA125 level,
      tuberculosis should always be kept on the list of differential diagnoses. A
      tissue diagnosis should always be obtained before treatment, regardless of
      initial image study and laboratory findings.

PMID- 10902230
TI  - Adult Wilms' tumor presenting as acute abdomen with elevated serum lactate
      dehydrogenase-4 and -5 isoenzymes: case report.
AB  - Wilms' tumor, an embryonic neoplasm, is the most frequent renal tumor in
      childhood but is rare in adults. The prognosis of adult Wilms' tumor is worse
      than pediatric Wilms' tumor. The preoperative diagnosis of adult Wilms' tumor is
      extremely difficult to make because diagnostic imaging techniques, such as
      intravenous pyelography, computed tomography, ultrasound, renal angiography, and
      nuclear magnetic resonance imaging, only confirm the presence of a renal mass.
      Diagnosis usually depends on histological characteristics, such as the presence
      of blastemic, epithelial, and mesenchymal components. A 27-year-old female
      presented with acute abdomen and with elevated serum lactate dehydrogenase (LDH)
      at 212 U/l (normal range: 47-140), and 2 of 5 LDH isoenzymes, namely LDH-4 at
      13.6% (normal range: 6.8%-10.2%) and LDH-5 at 20% (normal range: 6.5%-9.7%). In
      this patient, stage I Wilms' tumor was managed by radical nephrectomy. The levels
      of LDH returned to its normal range. In conclusion, in cases of acute abdomen
      with a renal mass in young adults, the possibility of Wilms' tumor should be
      considered. Serum LDH and its isoenzymes, LDH-4 and LDH-5, could be used as tumor
      markers for either differential diagnosis or monitoring the response of
      treatment.

PMID- 10902231
TI  - Endogenous Klebsiella pneumoniae endophthalmitis associated with prostate
      abscess: case report.
AB  - A young alcoholic and heavy smoker was admitted because of Klebsiella pneumoniae
      bacteremia. The abdominal and pelvic computed tomography with enhancement
      revealed an abscess in the right prostate. He experienced blurred vision of his
      left eye on the third day during admission. Initial ocular examination revealed
      mild reaction in the anterior chamber and vitreous as well as multiple Roth's
      spots in the retina. The administration of empirical antibiotics including
      cefazolin and gentamicin intravenously was changed to ceftriaxone and amikacin
      after ophthalmologic consultation. After parenteral antibiotics for 3 weeks, the
      systemic condition was controlled, and the vision remained stable. During the
      past decades, many cases of endogenous Klebsiella pneumoniae endophthalmitis
      associated with liver abscess were reported in Taiwan. However, documented
      reports of this condition associated with a prostate abscess are rare. This case,
      classified as posterior focal endogenous endophthalmitis, had good prognosis
      under appropriate antibiotic treatment. Early diagnosis and prompt therapy are
      important for control of sepsis and restoration of vision.

PMID- 10902232
TI  - Multiple pregnancy with adnexal torsion after in vitro fertilization: case
      report.

PMID- 10902233
TI  - When should asymptomatic bacteriuria in the elderly be treated?

PMID- 10902234
TI  - Cisapride: limited access and alternatives.
AB  - The withdrawal of cisapride from the market will present challenges for
      physicians treating patients with nocturnal heartburn, gastroparesis, and
      dyspepsia. However, alternatives to the drug exist, and it will continue to be
      available under a limited-access program for patients for whom other drug
      treatments fail.

PMID- 10902235
TI  - Preventing prescription drug abuse.
AB  - Prescription drug abuse is a problem with potentially grave consequences for
      patients and their families. Primary care physicians can play a major role in
      curbing prescription drug abuse by learning to recognize drug-seeking behavior
      and other warning signs, by educating patients about their drug regimens, and by
      setting firm but reasonable prescribing guidelines for their practices.

PMID- 10902236
TI  - Treatment strategies for hepatitis C: making the best of limited options.
AB  - Data from two recent major trials suggest that several changes in clinical
      practice would benefit hepatitis C patients, including viral genotyping to more
      accurately determine the duration of therapy, and timely RNA measurement to
      predict treatment response. Although the combination of interferon alfa-2b and
      ribavirin therapy has proved superior to interferon alone, the success of
      interferon-based therapies in eradicating hepatitis C is limited, and the quest
      for new strategies and treatments continues.

PMID- 10902237
TI  - Controversies in the diagnosis and treatment of gestational diabetes.
AB  - Uncontrolled gestational diabetes is associated with infant macrosomia and a
      lifelong risk of developing diabetes. Prompt diagnosis and aggressive management
      is therefore critical. All pregnant women should be screened for carbohydrate
      intolerance. Women with even minor abnormalities in blood sugar levels should be
      trained to monitor their glucose levels, rigorously control their diet, and use
      insulin if necessary. Exercise is also very beneficial.

PMID- 10902238
TI  - Lowering LDL in patients with heart disease: how aggressive should you be?

PMID- 10902239
TI  - Epidural spinal cord compression in cancer patients: diagnosis and management.
AB  - In most patients with spinal cord compression due to epidural metastasis, the
      initial symptom is progressive back pain with an axial or radicular distribution,
      but early symptoms are often nonspecific. Since the key prognostic factor is the
      neurologic status at the time of presentation, and since early complaints are
      often nonspecific, a high index of suspicion is needed to diagnose this
      complication early.

PMID- 10902240
TI  - A 41-year-old woman with confusion and unsteady gait.

PMID- 10902241
TI  - Gulf War syndrome.

PMID- 10902242
TI  - Evaluation and management of common running injuries.
AB  - Adults who run for sport or for pleasure often present to their primary care
      physician with musculoskeletal complaints. Rapid diagnosis and conservative
      management of common running injuries and referral of patients with injuries that
      have a propensity for morbidity, such as femoral neck stress fractures, are
      reviewed. Careful evaluation of the patient's running program and physical
      therapy are important components of management.

PMID- 10902243
TI  - Preventive medicine and screening in the elderly: working guidelines.
AB  - Preventive medicine is an attractive concept, but is insufficiently studied and
      emphasized, especially regarding the elderly. This working guideline for
      prevention and screening of common health problems of the elderly is based on
      existing recommendations and takes into account the continuing controversies and
      gaps in knowledge and research.

PMID- 10902244
TI  - Science, sense, and nonsense about HIV in Africa.

PMID- 10902245
TI  - Medical mycology in the UK: time to stop the dry rot.

PMID- 10902246
TI  - Is the polymerase chain reaction a useful tool or an expensive toy in culture
      negative endocarditis?

PMID- 10902247
TI  - Preventing transmission of bloodborne virus infections in prisons.

PMID- 10902248
TI  - Screening men for Chlamydia trachomatis infection: have we fully explored the
      possibilities?
AB  - Genital chlamydial infection is the commonest curable sexually transmitted
      disease in England and Wales. It is a major cause of pelvic inflammatory disease,
      ectopic pregnancy, and infertility. For this reason, research, health promotion,
      and disease prevention initiatives have focused on women. Screening women for
      chlamydial infection is concerned mainly with identifying and reducing
      complications among those already infected (secondary prevention), rather than
      with preventing new infections (primary prevention). Screening men for genital
      chlamydial infection, a strategy for preventing new infections in women, has been
      considered problematic because of the cost, the invasiveness of sampling
      procedures, and the need to screen in clinical settings. The availability of
      nucleic acid amplification diagnostic tests challenges these limitations and
      offers new opportunities for actively including men in disease prevention. This
      article reviews the arguments for and against screening men for genital
      chlamydial infection and discusses possible strategies for its implementation.

PMID- 10902249
TI  - Survey of raw egg use by home caterers.
AB  - Outbreaks of egg related salmonella infection continue to occur despite over ten
      years of national guidance on this subject. Fifty-four out of 70 registered home
      caterers in Cheshire responded to a telephone questionnaire, which revealed that
      a sixth prepared raw egg dishes containing shell eggs, none used pasteurised egg,
      and advice about storage of eggs and handwashing was not always followed. A
      postal questionnaire sent to 13 wholesalers and major supermarket chains showed
      that pasteurised egg was available in large packs from wholesalers but not from
      supermarkets. It is time to consider new approaches to reinforce advice about
      pasteurised egg use for raw egg dishes, storage, and measures to prevent cross
      contamination. These findings have implications for the training of home caterers
      and the general public.

PMID- 10902251
TI  - Survey of local authority approaches to investigating sporadic cases of suspected
      food poisoning.
AB  - Local authorities in England were surveyed in 1997 to document their approach to
      investigating sporadic cases of suspected food poisoning, the data they collect,
      and their objectives for doing so. Three hundred and nineteen of the 359
      authorities (89%) responded. The main objectives stated were to prevent spread of
      infection, detect outbreaks, educate the public, and identify risk factors for
      infection. Most outbreaks of food poisoning were detected as a result of
      complaints from members of the public. Investigation of Salmonella spp and Vero
      cytotoxin producing Escherichia coli O157 appeared to have a higher priority than
      campylobacter infection and viral gastroenteritis. Eighty-five per cent (266/311)
      of local authorities had agreed timescales for investigating cases and 54%
      (165/306) reported using computer technology to collate and analyse data on
      sporadic cases of food poisoning. Almost all (243/244) respondents supported the
      idea of having a new national system for the collation of such data and 79%
      (244/309) expressed interest in piloting a new standard form for enhanced
      surveillance of food poisoning.

PMID- 10902250
TI  - Four linked outbreaks of Salmonella enteritidis phage type 4 infection--the
      continuing egg threat.
AB  - Four outbreaks of Salmonella enteritidis phage type (PT) 4 occurred among guests
      at functions for which a single commercial caterer supplied food. Retrospective
      cohort studies were used to describe the epidemiology of three of these outbreaks
      and identify the vehicle(s) responsible. Of 172 guests at these three events, 47
      fitted the clinical case definition for illness and 24 cases were confirmed to
      have S. enteritidis PT4 infection. Food containing raw egg was identified
      epidemiologically as the likely vehicle of infection in two of the three
      outbreaks (odds ratios (OR) and 95% confidence intervals 9.1 (2.2-39.9) and 6.9
      (1.2-46.4)). Logistic regression analysis yielded OR = 10.7 (p = 0.0022) and OR =
      9.3 (p = 0.015) for egg consumption in two of the outbreaks. These outbreaks
      highlighted the continuing need to remind the public and commercial caterers of
      the potential high risks of contracting salmonella from shell eggs. Education of
      caterers includes advice to obtain eggs and other products from reputable and
      identifiable suppliers.

PMID- 10902252
TI  - Evaluation of a pilot standard questionnaire for the enhanced surveillance of
      sporadic cases of suspected food poisoning.
AB  - A national survey of local authorities, carried out in 1997, investigated how
      they dealt with sporadic cases of suspected food poisoning. A standard
      questionnaire for recording routine follow up information was then designed and
      piloted for three months in 30 local authorities in England. The questionnaire
      captured information on clinical and demographic details and exposure histories
      such as contact with animals, recreational exposure to water, and travel but was
      less successful at capturing information on domestic catering practices and food
      consumption. A successful surveillance questionnaire must be designed carefully
      to gather essential data without overburdening investigating officers.

PMID- 10902253
TI  - Evolution of a laboratory based system for investigating outbreaks of infectious
      intestinal disease.
AB  - In 1995 Preston Public Health Laboratory introduced an incident logging system
      intended to improve the investigation of suspected outbreaks of infectious
      intestinal disease. A unique incident log (Ilog) number assigned and issued to
      the reporting individual and other interested parties when the laboratory is
      informed of a potential outbreak is used to identify all associated specimens
      submitted to the laboratory and is quoted in all communications about the
      incident. The results are reviewed formally each month. Between January 1995 and
      December 1998, 349 potential outbreaks of infectious intestinal disease were
      investigated, 325 of which were considered to be general outbreaks. Small round
      structured viruses were identified in 45% of these outbreaks, salmonellas in 8%,
      and no pathogens in 35%. Data from the national surveillance scheme for general
      outbreaks of infectious intestinal disease included 104 general outbreaks in 1996
      and 1997 for the entire North West region, but our laboratory alone reported 184
      general outbreaks during that period. The Ilog system is a simple and effective
      means for reviewing data from outbreaks, and helps to coordinate their
      investigation.

PMID- 10902254
TI  - Laboratory policies on testing for rotavirus affect surveillance data. PHLS East
      Epidemiology and Virology Subcommittees.
AB  - The effect of different laboratory testing policies on the surveillance of
      rotavirus was assessed in eight laboratories between 1995 and 1998. In 1995, five
      laboratories tested all faecal specimens from children aged 5 years and under all
      year, two tested all specimens from children aged 4 years and under all year, and
      one tested all specimens from children aged 3 years and under between November
      and May only. Five laboratories changed their testing policy between 1995 and
      1998. By 1998, three tested all specimens from children aged 5 years and under
      all year and two from the same age group during the 'season' only. Three
      laboratories had unique policies: one tested all specimens from children aged 2
      years and under between January and June, one tested all specimens from children
      aged 4 years and under all year, and one tested specimens only on clinical
      request. The onset date of the rotavirus infection 'season' as determined by
      retrospective scrutiny of reported cases varied by up to 15 weeks between
      laboratories, starting as early as week 45 (November) and as late as week 13
      (March). Laboratories with more restrictive testing policies yielded fewer
      reports of rotavirus and changes in policy within a particular laboratory
      affected the number of reports. Temporal and geographic trends were visible, even
      within the relatively small area covered by this study, and showed how laboratory
      testing policies affect surveillance data.

PMID- 10902256
TI  - Survey of how public health doctors in the United Kingdom and Republic of Ireland
      investigate the effects of long-term exposure to point sources of chemicals.
AB  - Public health departments may need to investigate the health effects of long term
      exposures to chemicals from sources such as landfill sites and factories. Public
      health consultants responsible for communicable disease and environmental health
      and directors of public health in all health authorities and health boards in the
      United Kingdom and the Republic of Ireland were surveyed on behalf of a Faculty
      of Public Health Medicine guideline development group. The survey achieved a
      response rate of over 80%. Most public health doctors had investigated the health
      effects of long term exposure to chemicals, but many found it difficult to
      conduct effective and appropriate investigations in the face of community and
      political pressure. Most doctors acknowledged that they were responsible for
      investigating these problems, but wanted more epidemiological support, training,
      and guidance.

PMID- 10902255
TI  - Prevalence of HIV, hepatitis B, and hepatitis C antibodies in prisoners in
      England and Wales: a national survey.
AB  - Prisoners in eight of the 135 prisons in England and Wales were surveyed in 1997
      and 1998 to study the prevalence of and risk factors for transmission of
      bloodborne viruses in prison. Subjects voluntarily completed a risk factor
      questionnaire and provided oral fluid specimens for unlinked anonymous testing
      for the presence of antibodies to HIV, hepatitis C virus (HCV), and the core
      antigen of hepatitis B virus (HBc). Almost 8% (4778) of the total of 60,561
      prisoners were eligible and four fifths (3942) of those eligible took part. Among
      all those tested (3930) 0.4% (14) were positive for anti-HIV, 8% (308) for anti
      HBc, and 7% (293) for anti-HCV (the anti-HBc and anti-HCV prevalences were not
      adjusted for assay sensitivities of 82% and 80%, respectively). Twenty-four per
      cent (777/3176) of adult prisoners reported ever having injected drugs, 30% of
      whom (224/747) reported having injected in prison. Three quarters of those who
      injected in prison (167/224) shared needles or syringes. Among adult injecting
      drug users, 0.5% (4/775) had anti-HIV, 31% (240/775) anti-HCV, and 20% (158/775)
      anti-HBc. The presence of anti-HCV and anti-HBc was associated with injecting
      inside prison and number of previous times in prison. The results suggest that
      hepatitis viruses are probably being transmitted in prisons through sharing non
      sterile injecting equipment and that a risk of HIV transmission exists. Harm
      minimisation measures for the 6% of prisoners who continue to inject while in
      prison should be strengthened.

PMID- 10902257
TI  - Serological evidence of pertussis in patients presenting with cough in general
      practice in Birmingham.
AB  - Three hundred and fifty-six patients in a large suburban practice (registered
      population 10,400), were diagnosed clinically with acute laryngitis/tracheitis or
      whooping cough (acute spasmodic cough of three weeks duration) between March 1996
      and November 1997. Forty out of 145 who provided specimens for serological
      testing had evidence of recent infection with Bordetella pertussis. During the
      study a further 18 patients (mostly younger patients who presented early) had a
      diagnosis of pertussis confirmed by culture. Fifty-eight cases of pertussis in
      this population and time period was equivalent to an annual incidence of 330 per
      100,000, whereas statutory notifications of pertussis in England and Wales
      suggested an incidence of less than 4 per 100,000 in the same period. Whooping
      cough remains an important cause of respiratory illness in all age groups. These
      results are a reminder for general practitioners to be alert to the diagnosis and
      a prompt to reconsider national vaccination policy.

PMID- 10902259
TI  - Compliance with advice to boil drinking water during an outbreak of
      cryptosporidiosis. Outbreak Investigation Team.
AB  - All 2000 employees of a hospital in an area of the North Thames region where
      300,000 households were advised to boil tap water before consumption during a
      large outbreak of cryptosporidiosis were surveyed about compliance with and
      adverse events linked to the boil water notice. Eighty-five per cent (408/479) of
      respondents who lived in the boil water area said that they used boiled water
      while the notice was in place, 72% (347) used bottled water, and 12% (59) did not
      continue to boil water for the whole 16 days. Although 88% believed that they
      were following the advice, 20% washed food that would be eaten raw in unboiled
      tap water and 57% used it to clean their teeth. If a boil water notice is applied
      for more than a few days it may be helpful to issue a detailed follow up letter.

PMID- 10902258
TI  - Family outbreak of dysentery caused by a rhamnose non-fermenting, ONPG-negative
      strain of Shigella sonnei phage type 6.
AB  - Three members of a Scottish family, with no history of foreign travel but who had
      recently visited Bristol, were infected by a strain of Shigella sonnei of phage
      type 6 (PT 6) that did not ferment rhamnose and was negative for o-nitrophenyl
      beta-D-galactopyranoside (ONPG). The incident exposed limitations associated with
      commercial systems for the identification of strains of S. sonnei with atypical
      biochemical properties.

PMID- 10902260
TI  - Outbreak of hepatitis A in a special needs school in Kent: 1999.
AB  - In an outbreak of hepatitis A virus (HAV) infection in a special needs school
      salivary testing was used to identify those recently infected and those who were
      immune. The value of such testing as an epidemiological and outbreak control tool
      is discussed. HAV vaccine rather than human normal immunoglobulin was used to
      bring the outbreak under control.

PMID- 10902261
TI  - Problems of an automated testing system for hepatitis B.
AB  - False positive hepatitis B surface and e antigen results on the Abbott Axsym
      analyser are causing concern. All users of this technology should be aware of the
      problem.

PMID- 10902262
TI  - Distribution of tuberculosis cases in inner cities.

PMID- 10902264
TI  - Guidance on diphtheria.

PMID- 10902263
TI  - Lookbacks for HIV infected health care workers.

PMID- 10902265
TI  - Topley Online.

PMID- 10902266
TI  - Proteomics--discovering the protein constellation of the cell.

PMID- 10902267
TI  - Occupational standards in biomedical science and the promotion of professional
      portfolios.

PMID- 10902268
TI  - Safety training and legal liability.
AB  - Safety at work depends on knowledge of the hazards of the working environment and
      their effects. Training is needed to avoid, reduce, or manage the effects of
      these hazards. Health and safety legislation requires employers to provide staff
      with the knowledge needed for safety management and the confidence to deal with
      hazards at work. This article considers the general health and safety training
      requirements for different members of staff in terms of management and
      competence.

PMID- 10902269
TI  - Clostridium novyi is likely cause of 'serious unexplained illness' as cases
      continue to be reported.

PMID- 10902270
TI  - Safety of meningitis vaccine.

PMID- 10902271
TI  - NINSS reports on surgical site infection and hospital acquired bacteraemia.

PMID- 10902272
TI  - [Soluble Fas in acute rejection in patients with liver transplantation. Response
      to treatment].
AB  - It has been suggested that in the cellular rejection of hepatic graft, the lesion
      provoked by cytotoxic T-lymphocytes might be mediated by the Fas antigen/Fas
      ligand system, producing cell death by apoptosis. AIM: To determine whether
      soluble Fas (sFas) is increased during treatment and to evaluate response to
      treatment. MATERIAL AND METHODS: Fourteen patients with orthotopic liver
      transplantation who presented an episode of acute cellular rejection were
      studied. Serum levels of sFas were detected by enzyme-immunoanalysis at diagnosis
      and again 5 days after treatment was completed. As control groups, sFas was
      analyzed in 12 patients with liver transplantation without rejection and in 10
      healthy subjects. RESULTS: sFas levels were found to be significantly higher in
      patients with rejection than in those without rejection and in healthy subjects
      (24.2 +/- 39.1 vs. 2.8 +/- 4.0 vs. 0.6 +/- 1.5 UI/ml; p = 0.03). In patients with
      acute cellular rejection, immunosuppressive treatment significantly decreased
      sFas levels compared with basal values (24.2 +/- 39.1 vs. 9.9 +/- 30.2 UI/ml; p =
      0.005). A clear correlation between the serum levels of sFas, glutamate
      oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase/glutamic-pyruvic
      transaminase (GPT) and gamma-glutamyl transferase (GGT). CONCLUSIONS: a) The
      increase of sFas during rejection and the decrease in patients with a good
      evolution suggests that the Fas system may play an important role in the
      hepatocyte lesion produced by an apoptosis mechanism in these patients. b)
      Monitoring sFas could be useful in diagnosing rejection and in evaluating
      response to treatment.

PMID- 10902273
TI  - [Iron deficiency anemia in hospitalized males and postmenopausal females.
      Diagnostic approach].
AB  - Chronic bleeding from the gastrointestinal tract is assumed to be the most common
      cause of iron deficiency anemia in men and in postmenopausal women. AIM: The aim
      of this study was to assess the most frequent causes of chronic gastrointestinal
      bleeding in patients with iron deficiency anemia and to suggest a diagnostic
      endoscopic strategy that could be useful in clinical practice. METHODS: We
      studied 66 patients (48 women and 18 men), with a mean age of 73 who were
      admitted to our hospital from 1993 to 1996 because of unrelated signs and
      symptoms. Iron deficiency anemia was detected in a routine laboratory test.
      Patients had no symptoms of digestive disease. Children, pre-menopausal women and
      patients with a history of digestive disease of anemia of known origin were
      excluded. Diagnostic procedures included oral panendoscopy, colonoscopy and, in
      some cases, contrast radiology. In all patients follow-up was carried out between
      3 and 36 months after discharge. Patients were considered to have improved when
      hemoglobin values were normal, according to standard laboratory values. RESULTS:
      At least one lesion responsible for anemia was found in 46 patients (70%). Of
      these 46 patients, 31 presented a lesion in the upper digestive tract and 13
      presented a lesion in the lower digestive tract. Colon cancer was diagnosed in
      eight patients and gastrointestinal cancer in one. In the remaining two patients,
      peptic ulcer and colo-rectal cancer were found simultaneously. A diagnosis of
      "minor" lesions was made in 15 patients (23%) and in five patients (7%) no
      lesions were found that could have caused the bleeding. Both groups (minor
      lesions and undiagnosed patients) improved with iron therapy. CONCLUSIONS: Upper
      gastrointestinal lesions were the most frequent cause of iron-deficiency anemia,
      although colonoscopy is the best procedure for detecting gastrointestinal cancer
      and should be performed despite evident upper gastrointestinal bleeding.

PMID- 10902274
TI  - [Laparoscopic treatment of colorectal polyps].
AB  - Endoscopic removal is the treatment of choice for colorectal polyps. However,
      this therapeutic option is limited by the size of the tumor, sessile
      implantation, or technical impossibility. These cases are ideal for laparoscopic
      treatment because of the anatomy of the colon is and because the risk of
      manipulating a malignant lesion is lower. However, there is the added difficulty
      of identifying the lesion. In other cases, unsuspected neoplastic invasion of an
      endoscopically removed polyp makes surgery necessary. AIM: To evaluate the
      results of laparoscopic surgery in the treatment of colorectal polyps. MATERIAL
      AND METHODS: Between December 1997 and November 1999, 270 endoscopic
      polypectomies were performed. In 15 patients, endoscopic removal was technically
      impossible or contraindicated. These patients were treated laparoscopically. One
      patient who was found to have an invasive carcinoma following polypectomy was
      also treated laparoscopically. The technical characteristics of the operation
      (duration, conversion, morbi-mortality, postoperative stay, size of the polyp and
      number of ganglions) were analyzed and compared with 43 other laparoscopic
      operations in the colon carried out for other reasons (n = 43). RESULTS: In nine
      patients, surgery was indicated because of the size of the polyp, in three for
      technical reasons, in three for severe atypia and in one because of an invasive
      carcinoma following polypectomy. The operation was completed by laparoscopy in 15
      patients (94%). Ten right hemicolectomies, five sigmoidectomies and one anterior
      resection assisted by hand port were carried out. The diameter of the lesions was
      4.4 +/- 2.4 cm. Histological studies revealed carcinoma in situ in five,
      infiltrating carcinoma in two, non-malignant adenoma in six and lipoma in one.
      Comparison of the results of patients who underwent colectomy for polyps with
      those of the group who underwent surgery for other reasons revealed lower
      morbidity (24% vs. 22%) and need for conversion (7% vs. 16%), as well as a
      significant decrease in operating time (130 +/- 10 vs. 148 +/- 32 min, p < 0.05)
      and in postoperative stay (6.6 +/- 1.4 vs. 8.3 +/- 2.5 days, p < 0.02).
      CONCLUSION: Laparoscopic colonic resection is particularly suitable in the
      treatment of colorectal polyps.

PMID- 10902275
TI  - [Hereditary hemorrhagic telangiectasia with liver involvement].
AB  - Rendu-Osler-Weber syndrome, or hereditary hemorrhagic telangiectasia, is
      characterized by vascular alterations that tend to hemorrhage. We present a 56
      year-old woman, with a diagnosis of chronic liver disease of unknown origin 15
      years earlier, who came to our hospital as a liver transplantation candidate
      following hemorrhage due to esophageal varices. Rendu-Osler-Weber syndrome can
      affect the liver in several ways although vascular alterations can be
      distinguished from those produced in the liver parenchyma. The different types of
      vascular alterations in the liver may manifest as as telangiectasias, angiomas,
      aneurysms of the hepatic artery and fistulae between different vessels. This
      syndrome may also produce alterations in the liver parenchyma although the exact
      pathogenic mechanisms are unknown. There are three main forms of treatment:
      embolization of the branches of the hepatic artery, ligature of the hepatic
      artery and liver transplantation.

PMID- 10902276
TI  - [Vascular involvement of the colon in a patient with chronic hepatitis C virus
      infection].
AB  - We describe a case of vasculitis with colonic involvement/alterations associated
      with hepatitis C virus infection. Both the association of hepatitis C with
      vasculitis type periarteritis nodosa and the prominent involvement of the colon
      are infrequent. The presentation of this case--fever of unknown origin--as well
      as the difficulties of treating a patient who is a hepatitis C virus carrier are
      discussed.

PMID- 10902277
TI  - [Focal fatty liver lesions: infrequent ultrasonographic presentation].
AB  - We present case of focal fatty liver lesions. Echography images revealed multiple
      hyperechogenic lesions similar to those observed in metastatic disease.
      Aspiration was negative and diagnosis was based on the results of liver biopsy
      alone, carried out during laparoscopy. The difficulty of determining the etiology
      of this type of lesion by echography is discussed.

PMID- 10902278
TI  - [Intrahepatic cholestasis induced by amoxicillin alone].
AB  - We present a young, female patient with clinical and biochemical manifestations
      of acute cholestasis who had undergone a 10-day course of 1,500 mg/day
      amoxicillin 3 weeks before the consultation. Diagnosis was based on the absence
      of alcohol consumption, negative viral markers and antibodies, normal biliary
      tract, clinical and biochemical improvement when amoxicillin was withdrawn and
      liver biopsy with histological changes compatible with amoxicillin-induced acute
      cholestasis. Because hepatotoxicity induced by amoxicillin alone is rare, we
      believe it important to communicate this new case and to warn of this possible
      complication. We also stress that simple cholestasis induced by amoxicillin
      alone, as presented in this case, has been described in only one report,
      published 10 years ago.

PMID- 10902279
TI  - [Extrahepatic cholangiocarcinoma. Diagnostic difficulties and therapeutic
      options].

PMID- 10902280
TI  - [Anti-TNF antibodies in the treatment of intestinal inflammatory disease].

PMID- 10902281
TI  - [Toxic hepatitis caused by flutamide and hirsutism].

PMID- 10902282
TI  - [Atypical findings in nuclear magnetic resonance in a cirrhotic patient before
      and after liver transplantation].

PMID- 10902283
TI  - [Celiac disease: diagnostic value of endoscopic identification of micronodules in
      duodenal bulb].

PMID- 10902284
TI  - [Vaginal birth after cesarean: feasible and safe approach to reduce the
      percentage of cesarean sections in Mexico].

PMID- 10902285
TI  - [Breast cancer in Mexico. Is it a young women disease?].
AB  - Breast cancer in Mexico has the second place in frequency in general population
      (10.6%) as well as in females (16.4%). There has been found an increase in
      mortality from 3.6, in 1985, to 6 x 100,000 inhabitants, in 1994. Breast cancer
      diagnosis is made in advanced stages (III, IV, N.C.) in two out of three of our
      patients and a great proportion of them are younger than 50 years old. In order
      to know if age at diagnosis of breast cancer women in Mexico is similar of that
      of women of other countries, and in consequence, if breast screening has to be
      done as they have determined, we analyzed the age at diagnosis of 29,075 mexican
      women with breast cancer from 1993 to 1996. We found that median age of our
      patients was 51 years, one decade younger than that of European or white American
      women (60-64 years), and 45.5% of Mexican women are less than 50 years old at
      diagnosis of breast cancer, therefore, breast cancer screening indications
      adopted in Mexico, do not cover, not even theoretically, almost 50% of our women.
      It is mandatory to determine indications of breast screening according to our
      reality.

PMID- 10902286
TI  - [Acute fatty liver in pregnancy. Experience of 7 years].
AB  - OBJECTIVE: The purpose of this clinical investigation was to evaluate the
      frequency, clinical presentation, evolution, and maternal-fetal morbimortality of
      Acute Fatty Liver of Pregnancy (AFL). MATERIAL AND METHODS: Over a period of 7
      years from January 1990 to December 1996 the charts of patients with diagnosis of
      Gestational Acute Fatty Liver released from the Adult Intensive Care Unit of the
      Hospital Luis Castelazo Ayala of the Instituto Mexicano del Seguro Social were
      examined. The following information was retrieved: presenting symptoms, diagnosis
      on admission to the hospital and intensive care unit, evolution, laboratory,
      paraclinical, biopsy and serological findings, complications in mother and child,
      management and method of terminating pregnancy. RESULTS: Twelve cases of AFL of
      Pregnancy were detected. The disease was not suspected on hospital admission in
      the majority of the cases; all sought attention because of an obstetric
      complication requiring termination of pregnancy such as acute fetal distress or
      rupture of membranes. The average age of the patients was 25 years with an
      average gestational age of the fetuses of 36 weeks. Symptoms were presented one
      to seven days and consisted of jaundice in 100% of the cases, systemic
      hypertension in 75%, abdominal pain in 67%, nausea and vomiting in 50%,
      preeclampsia in 41% and consciousness disturbances in 17%. Outstanding laboratory
      findings included TGO 57 +/- 108 U/L, TGP 53 +/- 114 U/L, hypocholesterolemia 79
      +/- 30 mg/dL, total bilirubin 15.6 +/- 7 mg/dL, coagulation times prolonged
      almost two fold, leukocytosis, thrombocytopenia of 41,883 +/- 24,352 mm3,
      hypoglycemia of 51 +/- 16 mg/dL, and serum creatinine of 2.8 +/- 1.7 mg/dL.
      Ultrasound was performed in all patients but showed no specific alterations. CT
      scans on four patients demonstrated positive evidence in. Liver biopsies were
      performed on seven patients. The principal complications were DIC, hypoglycemia,
      acidosis, acute kidney failure, encephalopathy, three still births and one
      maternal death. CONCLUSIONS: AFL of Pregnancy should be suspected in pregnant
      patients in third quarter who present jaundice, nausea and vomiting and abdominal
      pain with an obstetric complication such as acute fetal distress or rupture of
      membranes with symptoms of preeclampsia and laboratory evidence of hypoglycemia
      and thrombocytopenia. Intensive Care unit treatment and pregnancy solution are
      diminishing keys for maternal-fetal morbimortality rates and complications.

PMID- 10902287
TI  - [Acceptance or refusal of abortion for maternal reasons. Survey of 3021 employees
      of the Federal Government].
AB  - A survey was conducted among 3021 employees from the Mexican Federal Government
      regarding their acceptance or rejection of abortion in five different
      circumstances. Socioeconomic information was obtained from the interviewed and
      the result was that 23% totally rejected abortion, and 6% accepted abortion in
      any situation. Abortion was accepted by 61% in case of pregnancy threatens the
      mother's life; 63% in case a single woman has been raped; 41% if there are so
      many children and such situation implies economic problems for the family; 13% if
      the couple prefers to wait for an economic improvement; and 18% if the couple has
      decided to have no more than two kids. Also from the interviewed, 16% pointed out
      that abortion must be an exclusive decision from the woman and 29% thought it
      must be a shared decision with the partner. Abortion is better accepted by young
      people, by couples with few children or living in free union and by people with
      higher education level and higher income. It is also better accepted by people
      with no religion, or people who do not attend religious services or by whom
      religion does not affect their decisions in life.

PMID- 10902288
TI  - [Diagnosis and treatment of the male factor in the age of intracytoplasmic sperm
      injection].
AB  - Currently, we are witnesses of the Assisted Reproductive techniques; advances
      reproductive goals have been reached with the Intracytoplasmic Sperm Injection
      (ICSI) in patients with male factor. However, micromanipulation techniques
      allowed the reproductive solution without an etiologic and/or physiopathologic
      diagnosis. The andrologic workup of the dynamic and functional sperm
      characteristics with the endocrine and urologic evaluation should be performed
      into the infertility management.

PMID- 10902289
TI  - [Perinatal mortality 1 in Colima, Col. Case-control study].
AB  - Perinatal mortality 1 (PM1) includes deads occurred from 28th week of gestation
      to 1st week of extrauterine life. The aim of this study was to describe, from
      medical records, clinical-epidemiological characteristics of 19 perinatal
      mortality 19 cases and 36 controls occurred in 1998 at a General Hospital.
      RESULTS: Interruption of the fetal-placental circulation, cardiopathy and
      ventricular hemorrhages were the main causes of PM1. There were no differences in
      cases and controls about maternal age 27.6 +/- 7 vs 28.8 +/- 5 years (p = 0.52),
      gestational age by amenorrhea: 39.2 +/- 1.4 vs 39.0 +/- 1.4 weeks (p = 0.82) and
      weight: 2892 +/- 769 vs 3352 +/- 549 g (p 0.03) respectively. In our study, the
      risk of PM1 was increased when history of one to four parity was present (OR =
      4.67, p = 0.03) and was decreased when history of nulliparity was present (OR =
      0.21, p = 0.03). Ten cases of 19 were mortinates, nine were hebdomadal deads.
      There was no difference in their characteristics: maternal age 26.1 +/- 5 vs 29.6
      +/- 8 years (p = 0.34), gestational age 37.7 +/- 3 vs 34.1 +/- 3 weeks (p = 0.05)
      and weight 3025 +/- 699 vs 2780 +/- 853 g (p = 0.53) respectively. Hebdomadal
      death occurred 44 +/- 5 hours after their born. Results demonstrate the
      importance of improving prenatal attention particularly on last weeks of
      gestation, even in normal pregnancies.

PMID- 10902290
TI  - [Changes in pituitary gonadotropins according to body mass index and adipose
      tissue distribution, in postmenopausal women receiving different types of hormone
      replacement therapy].
AB  - OBJECTIVE: To establish how gonadotrophins levels are modified according to body
      mass index (BMI) and waist-hip ratio (WHR), in postmenopausal women receiving
      different types of hormone replacement therapy (HRT). METHOD: Forty
      postmenopausal women were studied, and divided into two groups of 20 women each
      one (according to the HRT schedule administered (continuous or continuous
      combined). At baseline, three and six months, luteinizing hormone (Lh), follicle
      stimulating hormone (FSH) and estradiol (E2) serum levels were determined. The
      two groups were divided into two subgroups first according to BMI, and
      thereinafter according to WHR. Differences among the groups were assessed by Mann
      Whitney U test. The changes along each treatment group, were determined by
      Wilcoxon test. RESULTS: FSH and LH levels decreased and those of E2 increased at
      3 and 6 months after the beginning of treatment in each one of the HRT schedules,
      but without differences among them. Upon subdividing the groups, the changes were
      similar to the undivided group. CONCLUSIONS: It can be concluded that HRT
      modifies pituitary gonadotrophin secretion, but later changes exist in LH in
      obese and those with upper level body fat distribution.

PMID- 10902291
TI  - [Repeat cesarean section: a necessary procedure?].
AB  - The purpose of this study was to identify the clinical indications for the
      repeated cesarean section (RCS). In order to determine if the indication was an
      absolute or a relative one and to establish if it was justified. This is a cross
      sectional study of all patients with a previous cesarean delivery who underwent a
      RCS from January 1996 to December 1997 at the National Institute of Perinatology.
      Multiple pregnancies were excluded. According to the indication two groups were
      identified: those with an absolute indications and those with a relative one. In
      order to assess the differences between both groups data were analyzed through
      chi square test or Fisher's Exact test. During the study period there were 5,545
      cesarean deliveries, 664 were RSC (11.9%). Only 641 of the RCS complied with the
      inclusion criteria for the study. Average maternal age was 30 years. More than
      half the patients under study (57.2%) did not have any pathological condition
      during pregnancy, and the rest (42.7%) had at least one (preeclampsia, diabetes
      mellitus/gestational, chronic hypertension). Indications for the previous
      cesarean section were absolute in 25.9% and relative in 74.1% (p = 0.0006).
      Indications for the RCS were also predominantly relative (70.7%), with only
      29.3%) absolute (p = 0.0001). The main RCS indications were: elective (20.1%)
      cephalopelvic disproportion (17.8%), preeclampsia (15.4%), fetal distress (8%).
      Trial for vaginal delivery was undertaken in 65.4% of the absolute indications
      group and in 36.9% of the relative indications group (p = 0.0001). Low Apgar one
      minute and five minute scores were more frequent among the absolute indications
      group (p = 0.03 and p = 0.01 respectively). Newborns having had an absolute
      cesarean delivery indication entered the National Intensive Care Unit more
      frequently (53.6%) than those with relative indications (46.4%) (p = 0.001). The
      main indication for RCS in our hospital were relative, and thus it is possible to
      reduce the cesarean rate through a thorough assessment of all cases with a
      previous cesarean section, and by giving a delivery trial of all this patients.

PMID- 10902292
TI  - [High incidence of hyperestrogenemia and dyslipidemia in a group of infertile
      men].
AB  - The aim of this paper is to describe metabolic and endocrine alterations in the
      male, partners of infertile couples. One hundred and six consecutive men were
      taken in order to analyze their serum samples. Each serum sample was analyzed by
      duplicate for luteinizing hormone (LH), follicle-stimulating hormone (FSH),
      estradiol (E2), free-testosterone (T), 17 alpha-hydroxyprogesterone (17OHP),
      androstenedione (A), dehydroepiandrosterone-sulphate (DHEA-S), prolactin (PRL),
      insulin, glucose, total cholesterol and triclylcerides. The data analysis
      evidenced different metabolic or endocrine alterations in the group. A
      dysplipidemia incidence of 65% was found (isolated hypercholesterolemia, isolated
      triglyceridemia or both), where 80% of these patients were younger than 40 years.
      There was no correlation with obesity, overweight any endocrine alteration and
      the type of sperm alterations. There was a positive correlation between E2 and
      FSH (r = 0.67, p < 0.0001) in the group of 106 patients, which remained
      significant in the group of hyperestrogenic men (n = 27, r = 0.68, p < 0.0001),
      but not in men with normal serum estrogen levels (n = 79, r = 0.10, NS). Other
      alterations: obesity in 18%, overweight in 30.2%, diabetes mellitus 4.7%, glucose
      intolerance 15%, hypertension 26% (14/53), hypergonadotropic hypogonadism 3.8%
      (one of them with an Emty Sella syndrome). Unexpectedly only nine patients (8.4%)
      out of the 106 consecutive patients recluted did not have any of the metabolic or
      endodrine abnormalities here described. These are more significant since 83% of
      the patients are younger than 40 years. The most interesting non previously
      described finding was the positive correlation observed between E2 and FSH when
      estradiol levels exceeds 50 pg/mL.

PMID- 10902293
TI  - The impact of posthypnotic amnesia and directed forgetting on implicit and
      explicit memory: new insights from a modified process dissociation procedure.
AB  - The authors describe a study investigating the relationship between posthypnotic
      amnesia (PHA) and directed forgetting (DF) and their impact on implicit and
      explicit memory. This study adopted a recent modification of the process
      dissociation procedure to accommodate the cross-contamination of memory test
      performance by implicit and explicit memorial factors. Forty high and 40 low
      hypnotically susceptible participants were compared in PHA, DF, and control
      conditions on estimates of voluntary conscious (VCM), involuntary conscious
      (ICM), and involuntary unconscious memory (IUM) performance. Both groups showed
      significant decrements in VCM and ICM following instructions for DF, whereas only
      high susceptibles showed this decrement in the PHA condition; neither DF nor PHA
      affected IUM. Moreover, there was no relationship between forgetting in PHA and
      DF. Although both PHA and DF seem to prevent the conscious (i.e., explicit)
      expression of memorial information while leaving implicit memory intact, the
      mechanisms underlying these phenomena may nevertheless be different.

PMID- 10902295
TI  - Hypnotizability and absorption in a Danish sample: testing the influence of
      context.
AB  - This study tests the validity of a Danish translation of the Tellegen Absorption
      Scale (TAS) by investigating the correlation between scores on the TAS and a
      previously validated Danish translation of the Harvard Group Scale of Hypnotic
      Susceptibility (HGSHS:A) in a sample of 168 subjects. Mean TAS and HGSHS:A scores
      were comparable to those found in U.S. samples. The correlation between
      absorption and hypnotizability was calculated for scores obtained in the same
      session (n = 84) and for scores obtained independently in 2 sessions taking place
      2 to 12 months apart (n = 84). The results showed a significant relationship
      between absorption and hypnotizability when absorption was assessed in the
      hypnotic context. A significant association was also found when absorption and
      hypnotizability were assessed independently. The findings support the construct
      validity of the Danish translation of the TAS and reaffirm results of previous
      studies suggesting that absorption is an important predictor of hypnotizability.

PMID- 10902294
TI  - Treatment outcome expectancies and hypnotic susceptibility as moderators of pain
      reduction in patients with chronic tension-type headache.
AB  - The aim of this study was to determine whether hypnotic susceptibility (a)
      predicts pain reduction posttreatment and at follow-up independent of generic
      expectations of treatment outcome and mode of treatment and (b) predicts
      persistence of pain reduction during the follow-up period. In 169 patients with
      chronic tension-type headaches randomly allocated to either self-hypnosis or
      autogenic training, pain reduction posttreatment and at follow-up was
      significantly associated with hypnotic susceptibility independent of generic
      expectations of treatment outcome and treatment condition. Moreover, it was found
      that early responders obtained significantly higher hypnotic susceptibility
      scores than nonresponders, although there were no significant differences in
      hypnotic susceptibility between late responders in comparison to early and
      nonresponders. However, almost one fourth of those who were nonresponders
      posttreatment did respond at follow-up.

PMID- 10902296
TI  - Italian norms for the Stanford Hypnotic Susceptibility Scale, Form C.
AB  - This paper presents norms for an Italian translation of the Stanford Hypnotic
      Susceptibility Scale, Form C (SHSS:C; Weitzenhoffer & Hilgard, 1962). Archival
      data on hypnosis research subjects recruited over a 10-year period of research on
      hypnosis were pooled, resulting in an aggregate sample of 356 participants (263
      female and 93 male). Score distribution, item difficulty levels, and reliability
      of the SHSS:C were computed. Of this group, 218 subjects were administered the
      Harvard Group Scale of Hypnotic Susceptibility approximately 3 weeks prior to
      administration of the SHSS:C. The remaining 138 subjects received only the
      SHSS:C. Results suggest that the Italian version of the SHSS:C is a reliable and
      valid measure.

PMID- 10902297
TI  - The psychodynamic treatment of combat neuroses (PTSD) with hypnosis during World
      War II.
AB  - In a large Army hospital during World War II, a full-time program in hypnotherapy
      for battle trauma cases was developed. Symptoms included severe anxiety, phobias,
      conversions, hysterias, and dissociations. Many hypnoanalytic techniques were
      used, especially including abreactions. Good therapeutic results were frequent,
      as demonstrated by typical cases. There was no evidence that the abreactive
      procedure tended to retraumatize patients or initiate psychotic reactions.

PMID- 10902298
TI  - A sequential sampling scheme for detecting infestation levels of tracheal mites
      (Heterostigmata: Tarsonemidae) in honey bee (Hymenoptera: Apidae) colonies.
AB  - The introduction of parasitic honey bee mites, the tracheal mite, Acarapis woodi
      (Rennie) in 1984 and the Varroa mite, Varroa jacobsoni, in 1987, has dramatically
      increased the winter mortality of honey bee, Apis mellifera L., colonies in many
      areas of the United States. Some beekeepers have minimized their losses by
      routinely treating their colonies with menthol, currently the only Environmental
      Protection Agency-approved and available chemical for tracheal mite control.
      Menthol is also expensive and can interfere with honey harvesting. Because of
      inadequate sampling techniques and a lack of information concerning treatment,
      this routine treatment strategy has increased the possibility that tracheal mites
      will develop resistance to menthol. It is important to establish economic
      thresholds and treat colonies with menthol only when treatment is warranted
      rather than treating all colonies regardless of infestation level. The use of
      sequential sampling may reduce the amount of time and effort expended in
      examining individual colonies and determining if treatment is necessary.
      Sequential sampling also allows statistically based estimates of the percentage
      of bees in standard Langstroth hives infested with mites while controlling for
      the possibility of incorrectly assessing the amount of infestation. On the
      average, sequential sampling plans require fewer observations (bees) to reach a
      decision for specified probabilities of type I and type II errors than are
      required for fixed sampling plans, especially when the proportion of infested
      bees is either very low or very high. We developed a sequential sampling decision
      plan to allow the user to choose specific economic injury levels and the
      probability of making type I and type II errors which can result inconsiderable
      savings in time, labor and expense.

PMID- 10902299
TI  - Field evaluation of neem and canola oil for the selective control of the honey
      bee (Hymenoptera: Apidae) mite parasites Varroa jacobsoni (Acari: Varroidae) and
      Acarapis woodi (Acari: Tarsonemidae).
AB  - Neem oil, neem extract (neem-aza), and canola oil were evaluated for the
      management of the honey bee mite parasites Varroa jacobsoni (Oudemans) and
      Acarapis woodi (Rennie) in field experiments. Spraying neem oil on bees was more
      effective at controlling V. jacobsoni than feeding oil in a sucrose-based matrix
      (patty), feeding neem-aza in syrup, or spraying canola oil. Neem oil sprays also
      protected susceptible bees from A. woodi infestation. Only neem oil provided V.
      jacobsoni control comparable to the known varroacide formic acid, but it was not
      as effective as the synthetic product Apistan (tau-fluvalinate). Neem oil was
      effective only when sprayed six times at 4-d intervals and not when applied three
      times at 8-d intervals. Neem oil spray treatments had no effect on adult honey
      bee populations, but treatments reduced the amount of sealed brood in colonies by
      50% and caused queen loss at higher doses. Taken together, the results suggest
      that neem and canola oil show some promise for managing honey bee parasitic
      mites, but the negative effects of treatments to colonies and the lower efficacy
      against V. jacobsoni compared with synthetic acaricides may limit their
      usefulness to beekeepers.

PMID- 10902300
TI  - Survival of honey bee (Hymenoptera: Apidae) spermatozoa stored at above-freezing
      temperatures.
AB  - The development of practical techniques for the storage of honey bee, Apis
      mellifera L., semen would significantly improve our ability to breed for
      desirable genotypes and maintain genetic diversity in populations. Artificial
      insemination of queens has been possible for some time, but the semen used is
      usually freshly collected, or held for < 1 wk at room temperature. I examined the
      limitations of spermatozoal survival at nonfrozen temperatures. Pooled, diluted
      semen was stored in sealed capillary tubes at room temperature (25 degrees C) or
      in a refrigerator set to 12 degrees C, for periods up to 1 yr. Survival of
      spermatozoa was assayed by a dual fluorescent staining technique using SYBR-14
      and propidium iodide stains, which readily distinguishes live and dead cells. No
      significant loss of viable spermatozoa occurred within the first 6 wk. Between
      weeks 6 and 9, the percent live spermatozoa fell from 80 to 58%, and remained at
      that level until after 39 wk. By week 52, samples at room temperature, but not at
      12 degrees C, fell to 18.9% live spermatozoa. Nonfrozen storage of honey bee
      semen has potential for short-term preservation of germplasm, however several
      factors need to be studied further to optimize survival rates.

PMID- 10902301
TI  - Enhancement in activity of homologous and heterologous baculoviruses infectious
      to beet armyworm (Lepidoptera: Noctuidae) by an optical brightener.
AB  - The nuclear polyhedrosis virus (NPV) from the beet armyworm, Spodoptera exigua
      (Hubner) (SeMNPV), was the most active virus tested against the beet armyworm
      (LC50 = 4.1 PIBs/mm2), followed by nuclear polyhedrosis viruses from the alfalfa
      looper, Autographa californica (Speyer) (AcMNPV; LC50 = 92.6 PIBs/mm2), and the
      celery looper, Anagrapha falcifera (Kirby) (AfMNPV; LC50 = 195.7 PIBs/mm2). In
      the case of the nuclear polyhedrosis virus from the bollworm, Helicoverpa
      armigera (Hubner), LC50s could only be obtained for five/six replicates, whereas
      LC50s could only be obtained for two/six replicates for the nuclear polyhedrosis
      virus from the wax moth, Galleria mellonella (L.) (GmMNPV). When an optical
      brightener Tinopal LPW was added to virus suspensions, LC50 values were reduced
      by 130-fold for both SeMNPV and AcMNPV and by 300-fold for AfMNPV. The addition
      of Tinopal LPW greatly increased the activities of HaMNPV and GmMNPV. In terms of
      speed of kill, Tinopal LPW reduced the LT50s for all nuclear polyhedrosis viruses
      by 30-40%.

PMID- 10902302
TI  - Effect of insecticides on Trichogramma exiguum (Trichogrammatidae: Hymenoptera)
      preimaginal development and adult survival.
AB  - The effect of insecticides on Trichogramma exiguum Pinto & Platner emergence,
      adult survival, and fitness parameters was investigated. Insecticides tested were
      lambda cyhalothrin, cypermethrin, thiodicarb, profenophos, spinosad,
      methoxyfenozide, and tebufenozide. All insecticides, with the exception of
      methoxyfenozide and tebufenozide, adversely affected Trichogramma emergence from
      Helicoverpa zea (Boddie) host eggs when exposed at different preimaginal stages
      of development (larval, prepupal, or pupal). Regardless of the developmental
      stage treated, none of the insecticides tested had a significant effect on the
      sex ratio or frequency of brachyptery of emerged females. However, the mean life
      span of emerged T. exiguum females significantly varied among insecticide
      treatments, and was significantly affected by the developmental stage of
      parasitoid when treated. Based on LC50 values, spinosad and prophenofos were the
      most toxic compounds to female T. exiguum adults, followed by lambda cyhalothrin,
      cypermethrin, and thiodicarb. Insecticides field-weathered for four to 6 d on
      cotton leaves showed no activity against female T. exiguum adults.

PMID- 10902303
TI  - Potential for integrating eleven agricultural insecticides with the predatory bug
      Pristhesancus plagipennis (Hemiptera: Reduviidae).
AB  - A problem for growers attempting to implement integrated pest management programs
      is the lack of information regarding the compatibility of insecticides with
      natural enemies. To provide information about this problem, we evaluated the
      acute and residual effects of 11 commonly used insecticides on nymphs of
      Pristhesancus plagipennis (Walker) under both laboratory and field conditions.
      For each insecticide, the length of time that weathering residues caused > 50%
      mortality was evaluated and compared against the LC50 (acute-toxicity) divided by
      the recommended field rate. Plots thus combined the acute and residual toxicity
      of each insecticide. Results suggested that carbaryl, esfenvalerate, endosulfan,
      and deltamethrin had low residual and acute toxicity to P. plagipennis, whereas
      chlorpyrifos, methomyl, and monocrotophos were highly toxic at low concentrations
      and left persistent harmful residues. Cypermethrin, methidathion, malathion, and
      dimethoate were moderately toxic. The potential use of these insecticides to
      supplement the control activity of P. plagipennis is discussed.

PMID- 10902304
TI  - Performance of a pyrethroid-resistant strain of the predator mite Typhlodromus
      pyri (Acari: Phytoseiidae) under different insecticide regimes.
AB  - An organophosphate pyrethroid-resistant strain of Typhlodromus pyri Scheuten
      imported from New Zealand was reared on potted apple trees in an outdoor
      insectary. From 1988 to 1995, the population was selected one to three times per
      year with a dilute solution (1.7 ppm) of the pyrethroid cypermethrin. Petri dish
      bioassays with cypermethrin in 1995 indicated that the insectary-reared T. pyri
      had an LC50 of 81 ppm versus 0.006 ppm for native T. pyri taken from a research
      orchard. The bioassays suggested that recommended orchard rates of cypermethrin
      would cause heavy mortality in native populations of T. pyri but only moderate
      losses in the imported New Zealand strain. Bioassays in 1996 with the
      organophosphate insecticide dimethoate indicated both New Zealand and native T.
      pyri were susceptible and that recommended orchard rates of dimethoate likely
      would cause high mortality of T. pyri in apple orchards. These findings from
      bioassays were supported by data from orchard trials. In June and July 1993,
      insectary-reared New Zealand T. pyri were placed on five apple trees in each of
      eight 38-tree plots in the research orchard. In late August 1994, New Zealand T.
      pyri from orchard trees that had been sprayed twice by airblast sprayer with the
      full recommended rate of 50 g (AI)/ha (83 ppm) cypermethrin were placed on the
      other 33 trees in each of six plots. In the summers of 1994-1996, plots were
      treated with one of the following insecticide regimes: (1) conventional
      integrated pest management (IPM) (registered neurotoxic insecticides considered
      harmless or slightly toxic to T. pyri); (2) advanced IPM (use of newer, more
      selective insecticides); (3) pyrethroid (at least one full-rate application of
      cypermethrin); (4) dimethoate; and (5) dimethoate plus pyrethroid. Densities of
      European red mite, Panonychus ulmi (Koch), were highest in all plots treated with
      dimethoate and in pyrethroid plots not yet inoculated with New Zealand T. pyri.
      Densities of apple rust mite, Aculus schlechtendali (Nalepa), and of the
      stigmaeid predator Zetzellia mali (Ewing) were highest in plots treated with
      dimethoate and were nearly absent in the IPM plots. Densities of T. pyri were
      high enough for effective biocontrol in the IPM plots and in the pyrethroid plots
      1-2 yr after release of the New Zealand strain, provided pyrethroid was applied
      just before the resistant strain was released in the orchard. A recurring theme
      of this study was the generally negative association between densities of
      phytophagous mites and those of T. pyri, suggesting the ability of this predator
      to suppress their prey. In contrast, the positive association between
      phytophagous mites and Z. mali suggests the inability of this predator to
      regulate their prey at least under the conditions of this study.

PMID- 10902305
TI  - Potential of entomopathogenic nematodes for biological control of Acalymma
      vittatum (Coleoptera: Chrysomelidae) in cucumbers grown in conventional and
      organic soil management systems.
AB  - Acalymma vittatum (F.) is the primary insect pest of fresh-market cucumber and
      melon crops in much of the eastern United States because of their herbivory and
      interactions with several diseases, most notably bacterial wilt. A study was
      conducted to determine how soil management affects viability and infectivity of
      an entomopathogenic nematode that may be used for the control of A. vittatum.
      Dose-mortality curves under laboratory conditions suggested several Steinernema
      spp. as potential biocontrol agents. Field injections combined with soil
      bioassays showed that Steinernema riobravis Cabanillas, Poinar & Raulston
      (Rhabditus: Steinernematidae) longevity exceeded A. vittatum immature development
      time in both conventional and organic soil management systems. Mean root length
      densities of cucumbers increased in both soil management systems with the
      inclusion of nematodes. Soil management alone also influenced A. vittatum larval
      survivorship, with higher survival rates in the organic compared with the
      conventional soil management system. A 50% reduction in A. vittatum larval
      survival rates in both soil management systems, as determined by adult A.
      vittatum emergence, demonstrated the potential of incorporation of
      entomopathogenic nematodes for integrated pest management of diabroticites in
      commercial cucumber production.

PMID- 10902306
TI  - Field evaluation of soybean engineered with a synthetic cry1Ac transgene for
      resistance to corn earworm, soybean looper, velvetbean caterpillar (Lepidoptera:
      Noctuidae), and lesser cornstalk borer (Lepidoptera: Pyralidae).
AB  - A transgenic line of the soybean 'Jack', Glycine max (L.) Merrill, expressing a
      synthetic cry1Ac gene from Bacillus thuringiensis variety kurstaki (Jack-Bt), was
      evaluated for resistance to four lepidopteran pests in the field. Jack-Bt and
      genotypes serving as susceptible and resistant controls were planted in field
      cages and artificially infested with larvae of corn earworm, Helicoverpa zea
      (Boddie), and velvetbean caterpillar, Anticarsia gemmatalis (Hubner), in 1996,
      1997, and 1998, and also with soybean looper, Pseudoplusia includens (Walker), in
      1996. Susceptible controls included Jack (1996-1998), 'Cobb' (1996), and Jack-HPH
      (1996). GatIR 81-296 was used as the resistant control in all 3 yr. Compared with
      untransformed Jack, Jack-Bt showed three to five times less defoliation from corn
      earworm and eight to nine times less damage from velvetbean caterpillar.
      Defoliation of GatIR 81-296 was intermediate between that of Jack and Jack-Bt for
      corn earworm, and similar to that of Jack for velveltbean caterpillar. Jack-Bt
      exhibited significant, but lower resistance to soybean looper. Jack-Bt also
      showed four times greater resistance than Jack to natural infestations of lesser
      cornstalk borer, Elasmopalpus lignosellus (Zeller), in conventional field plots
      at two locations in 1998. Data from these experiments suggest that expression of
      this cry1Ac construct in soybean should provide adequate levels of resistance to
      several lepidopteran pests under field conditions.

PMID- 10902307
TI  - An economic comparison of biological and conventional control strategies for
      whiteflies (Homoptera: Aleyrodidae) in greenhouse poinsettias.
AB  - The objective of this study was to evaluate the costs of biologically controlling
      infestations of silverleaf whitefly, Bemisia argentifolii Bellows & Perring, in
      New England greenhouse operations on poinsettia, Euphorbia pulcherrima Wild, ex
      Koltz, using the parasitic wasp Encarsia formosa Gahan (Nile Delta strain).
      Partial budget analysis was used to compare costs for conventional verses
      biological control regimens. Four alternative whitefly control budgets are
      developed; two conventional chemical-based control budgets formulated with and
      without the use of imidacloprid, and two biological control budgets which
      demonstrate the impact of possibly greater pest monitoring efforts necessary to
      implement this type strategy successfully. The analysis shows that biological
      whitefly control costs were > 300% greater than conventional chemical-based
      control strategy costs. Most of this increase is caused by the higher costs of
      Encarsia formosa as the material control input. If monitoring costs are held
      constant across different strategies, labor costs actually decline for biological
      control. This is because of a significant reduction in the number of control
      applications made and the relatively lower cost of applying E. formosa. If more
      extensive monitoring efforts are required to implement biological control
      successfully, labor costs increase by 56% over the conventional pre-imidacloprid
      regimen. Based on these results, the authors conclude that cheaper and more
      reliable means of producing E. formosa must be developed before this strategy
      will become economically viable for commercial poinsettia greenhouse production.

PMID- 10902308
TI  - Efficiency of flight interception traps for adult Colorado potato beetles
      (Coleoptera: Chrysomelidae).
AB  - Interception traps have been used to monitor and sample Colorado potato beetle,
      Leptinotarsa decemlineata (Say), populations in flight, but the efficiency of
      these traps was unknown. The efficiency of interception window traps is limited
      because flying adults avoid the traps and may bounce off the trap without being
      collected. All trap types tested were avoided in flight chamber tests, including
      those constructed of transparent Plexiglas or yellow wood boards. A larger screen
      trap and a harp trap designed to reduce detection were also avoided by the
      beetles in flight. None of the traps provide a direct estimate of the number of
      adults randomly flying in the trap area. The highest level of efficiency for
      window traps was obtained with the yellow trap, which caught 16% of the expected
      flying population. Harp and screen traps without frames intercepted 60-62% of the
      expected flying population. The presence of a frame did not increase
      significantly the avoidance of the screen and harp traps by beetles in flight.
      Recommendations are made to maintain or increase the efficiency of some traps.

PMID- 10902309
TI  - Foraging resources of adult Mexican corn rootworm (Coleoptera: Chrysomelidae) in
      Bell County, Texas.
AB  - Pollen analyses were used to determine pollen foraging resources of adult Mexican
      corn rootworms, Diabrotica virgifera zeae Krysan & Smith, captured near Temple,
      Bell County, TX, in 1996 and 1997. In 1996, adult Mexican corn rootworms were
      captured in a corn, Zea mays L., field. In 1997, nine locations outside of
      cornfields were added. Overall, 92% of the beetles (n = 1,323) contained pollen.
      More than 142,000 pollen grains were counted, representing 45 families, 63
      genera, and 27 species. Overall, in 1996, noncorn grass pollen (70%) occurred in
      the greatest percentage of total pollen followed by corn (17%), then nongrass
      pollen (13%). In 1997, noncorn grass pollen (76%) had the greatest percentage,
      then nongrass (18%), and finally corn pollen (6%). Corn pollen was found in 34%
      of the beetles in 1996 and 26% in 1997. Fifteen Asteraceae taxa were encountered
      including sunflower, Helianthus annuus L. Thirteen Fabaceae were found including
      soybean, Glycine max L. Mexican corn rootworm adults foraged mainly on noncorn
      grass pollen, but also foraged on pollen from a large diversity of plant species,
      indicating that noncorn pollen may play a role in the food habits of Mexican corn
      rootworm adults.

PMID- 10902310
TI  - Visual and olfactory stimuli and fruit maturity affect trap captures of Oriental
      fruit flies (Diptera: Tephritidae).
AB  - An effective lure-and-kill trap is a potentially important instrument in
      monitoring and controlling oriental fruit flies, Bactrocera dorsalis (Hendel). A
      number of experiments were performed in an orchard of commercial guava, Psydium
      guajava L., to determine how fly captures are affected by combining visual and
      olfactory stimuli, and by the timing of trap deployment relative to host
      phenology. Baiting sticky Ladd traps with hydrolyzed liquid protein significantly
      increased the number of captured flies. Mostly male flies were caught in the
      absence of mature guava fruit, whereas mostly female flies were caught when ripe
      fruit was abundant. These results suggest that an effective oriental fruit fly
      trap should include both visual and olfactory lures, and that proper timing of
      trap deployment can be an important factor in monitoring female abundance in
      oriental fruit fly populations.

PMID- 10902311
TI  - Monitoring and modeling of field infestation and damage by the maize ear borer
      Mussidia nigrivenella (Lepidoptera: Pyralidae) in Benin, West Africa.
AB  - In many countries in West Africa, the pyralid ear borer Mussidia nigrivenella
      Ragonot occasionally causes severe damage to pre- and postharvest maize. Between
      1992 and 1995, the distribution of and damage caused by M. nigrivenella were
      studied in Benin using survey data and an on-station field experiment. The borer
      was distributed across the whole country, and at maturity an average 25% of the
      ears sampled in maize fields were infested. Damage levels varied with agro
      ecological zones and were highest in the Guinea Savannas. However, borer-related
      yield losses were comparatively low. Three applications of cypermethrin over the
      growing season did not provide sufficient control in the on-station field
      experiment. A model was developed to estimate maize losses caused by M.
      nigrivenella, using the percentage of infested ears, which explained 93% of the
      variance. Extrapolation of field data indicated a 25% yield loss once a 100%
      infestation of maize ears was reached. For surveys in maize fields the model is a
      valid tool for a rapid assessment of crop losses caused by M. nigrivenella.

PMID- 10902312
TI  - Simulated predictions of insect phenological events made by using mean and median
      functional lower developmental thresholds.
AB  - A computer-simulated study was conducted to determine whether mean or median
      functional lower developmental thresholds and required degree-days were superior
      for predicting the dates on which insect phenological events occurred. In
      addition, these simulations allowed us to determine if the type of year
      (weatherwise) influenced those predictions. Results indicated that when median
      functional lower developmental thresholds and required degree-days were used
      their predictions were closer to the dates on which the phenological events
      occurred than were predictions that were made using mean thresholds and required
      degree-days. Also, the predictions of phenological events made when using median
      functional lower developmental thresholds and required degree-days were not
      strongly influenced by the type of year. However, the influence of type of year
      was quite strong when predictions were made when using mean thresholds and
      required degree-days. The variability in predictions that were made when using
      median functional lower developmental thresholds and required degree-days was
      greater than the variability in predictions that were made when using mean
      thresholds and required degree days. However, the increased variability was
      caused by many predictions being closer to, rather than farther from, the actual
      dates on which the phenological events occurred. Based on these findings, we
      suggest that median functional lower developmental thresholds, along with median
      required degree-days, be considered for use when predicting insect phenological
      events in the field.

PMID- 10902313
TI  - Insecticidal activity of photoactive dyes to American and migratory grasshoppers
      (Orthoptera: Acrididae).
AB  - Many photoactive dyes are relatively nontoxic to vertebrates despite their
      insecticidal properties. Several photoactive dyes known to be toxic to some
      groups of insects were evaluated at various concentrations for toxicity to
      American and migratory grasshoppers in laboratory and field studies. Rose bengal
      and phloxine B were effective at inducing mortality of grasshoppers when applied
      at 2 and 5% to bran bait, though erythrosin B and uranine were ineffective.
      Partial replacement of phloxine with uranine in dye mixtures resulted in no
      significant loss of efficacy. Some indication of feeding inhibition was observed
      at high dye concentrations, so minimum effective dosages, probably 2%, are
      optimal. Phloxine B and rose bengal appeared to be stable upon exposure to
      sunlight, and able to withstand at least 24 h of sunlight without significant
      degradation. Dyes such as phloxine B could be a viable grasshopper control agent
      for small or medium-sized grasshopper species because mortality can be induced by
      consumption of a single flake dusted with 5% dye, and yet pose little hazard to
      vertebrates. Large species such as American grasshopper must consume several
      flakes before mortality is induced.

PMID- 10902314
TI  - Toxicity of insecticides for control of freshwater Culex annulirostris (Diptera:
      Culicidae) to the nontarget shrimp, Caradina indistincta (Decapoda: Atyidae).
AB  - Laboratory evaluations were conducted in southeastern Queensland, Australia, to
      determine the toxicities of two organophosphate compounds (temephos and
      pirimiphos-methyl), an insect growth regulator (s-methoprene), and an
      entomopathogenic bacterium (Bacillus thuringiensis variety israelensis de Barjac
      [B.t.i.]) to Culex annulirostris (Skuse), an Australian freshwater mosquito
      vector of arboviruses, and to Caradina indistincta Calman, a co-habiting
      nontarget shrimp species. S-methoprene and B.t.i. were safest for Cx.
      annulirostris control with lethal dose ratios (LC95 nontarget/LC95 target) of
      3,300 and 846,000, respectively. In contrast, lethal dose ratios for temephos and
      pirimiphos-methyl were 0.05 and 0.00005, respectively, suggesting that they are
      environmentally unsuitable. Based on their high lethal dose ratios, s-methoprene
      and B.t.i. are recommended for control of larval Cx. annulirostris in Australian
      freshwater habitats.

PMID- 10902315
TI  - Pre- and postharvest effects of lufenuron on Epiphyas postvittana (Lepidoptera:
      Tortricidae).
AB  - First-, third-, and fifth-instar Epiphyas postvittana (Walker) were exposed to a
      range of lufenuron concentrations (0-200 ppm) incorporated into synthetic diet
      and their subsequent development and mortality responses were determined. For all
      instars the greatest change in mortality response occurred over lufenuron
      concentrations < or = 3 ppm. However, third and fifth instars displayed an
      increase in mortality earlier than first instars, and were more sensitive to the
      lower lufenuron concentrations in this range. Only first and third instars
      subjected to < or = 2.5 ppm lufenuron survived the 26-d exposure trial. No larvae
      first exposed to lufenuron as first or third instars survived to pupation if
      ingesting concentrations of > or = 1 and > or = 3 ppm, respectively. Consumption
      of lower lufenuron concentrations by these larvae delayed pupation and resulted
      in pupal deformity. In contrast, fifth instars subjected to 100 ppm were capable
      of surviving the 26-d trial period and displayed a slower progressive reduction
      in survival to pupation with increase in lufenuron concentration. Also in
      contrast to more immature stages, fifth instars exposed to lufenuron developed
      more rapidly to pupation than larvae not exposed to the insect growth regulator
      (IGR), and all resulting pupae were normal. Third instars were exposed to
      sublethal lufenuron concentrations (0-3 ppm) for 4 d and the fourth-instar
      survivors subjected to a controlled atmosphere cold storage treatment (2% O2, 2%
      CO2, 0.6 degree C). Larvae ingesting diet containing 0.5 ppm (and to a lesser
      extent 1 ppm) lufenuron required longer exposure to the postharvest treatment to
      achieve > or = 95% mortality than larvae not ingesting the IGR. However, the
      analogous mortality response of larvae exposed to 3 ppm lufenuron was comparable
      to the control.

PMID- 10902316
TI  - Sublethal acute and chronic exposure of Colorado potato beetle (Coleoptera:
      Chrysomelidae) to the delta-endotoxin of Bacillus thuringiensis.
AB  - Sublethal exposure of Colorado potato beetle, Leptinotarsa decemlineata (Say),
      larvae to the delta-endotoxin of Bacillus thuringiensis variety tenebrionis
      (Berliner) caused a dose-dependent reduction in feeding and weight gain when
      tested in a leaf disk bioassay. The highest doses of chronic (continuous-lower
      concentration) exposure resulted in peak foliage consumption on day 1 as compared
      with peak consumption on days 3 and 4 when exposure was acute (24-h higher
      concentration). Dose and exposure regimen interacted significantly in their
      effects on the extension of development. When development time was analyzed
      separately for each exposure regimen, only acute exposure caused significant
      delays in development that extended through to adult eclosion. The efficiency of
      conversion of ingested material to biomass (ECI) declined significantly with both
      exposure regimens. The lethal and most sublethal effects of exposure to delta
      endotoxin were not cumulative, in that similar total doses, whether delivered
      acutely or chronically, produced different effects. Female adults that survived
      acute and chronic exposure to delta-endotoxin as larvae had significantly reduced
      weight and longevity, and tended to produce fewer eggs (45 and 44% reductions in
      acute and chronic exposures, respectively) when compared with control adults. The
      intrinsic rate of increase (r) and net reproductive rate (R0) also appeared to be
      reduced.

PMID- 10902317
TI  - Cotton boll abscission and yield losses associated with first-instar bollworm
      (Lepidoptera: Noctuidae) injury to nontransgenic and transgenic Bt cotton.
AB  - Field tests were conducted in northeastern Louisiana to determine the effects of
      infestations by Helicoverpa zea (Boddie) on cotton bolls of varying ages. First
      instars were caged on bolls of nontransgenic ('Deltapine 5415') or transgenic
      Bacillus thuringiensis Berliner variety kurstaki (Bt) ('NuCOTN 33B') cotton from
      29 June to 11 August during 1997 and 1998. Deltapine 5415 bolls that accumulated
      179 (7.2 d), 281 (11.2 d), and 253 (10.1 d) heat units beyond anthesis were safe
      from bollworm-induced abscission at 72 h after infestation, 7 d after
      infestation, and at the time of harvest, respectively. NuCOTN 33B bolls that
      accumulated 157 (6.3 d), 185 (7.4 d), and 180 (7.2 d) heat units beyond anthesis
      were safe from bollworm-induced abscission at 72 h after infestation, 7 d after
      infestation, and at the time of harvest, respectively. Bollworm larvae reduced
      seedcotton weights of Deltapine 5415 bolls that accumulated between 58.5 (2.3 d)
      and 350.5 (14.0 d) heat units beyond anthesis. Seedcotton weights of NuCOTN 33B
      bolls that accumulated between 0 and 281 (11.2 d) heat units beyond anthesis were
      reduced by bollworm injury. Deltapine 5415 and NuCOTN 33B bolls that accumulated
      426.5 (17.1 d) and 299.5 (12.0 d) heat units beyond anthesis, respectively,
      before infestation were not injured by first-instar bollworm larvae. These data
      provide information about late-season insecticide termination strategies for
      bollworms on nontransgenic and transgenic Bt-cotton. This, in turn, will help
      pest managers determine when insecticides are no longer economical during the
      late season.

PMID- 10902318
TI  - Dynamics and seasonal abundance of stink bugs (Heteroptera: Pentatomidae) in a
      cotton-soybean ecosystem.
AB  - Two soybean varieties (early-maturing group V and late-maturing group VII) and
      two cotton varieties (conventional and transgenic (Bt) were grown in adjacent
      replicated large field plots (approximately 0.1 ha each) at two locations for 3
      yr. The dynamics and relative abundance of phytophagous stink bugs within these
      two crops were observed. The most abundant pentatomid species in both crops for
      all 3 yr were Nezara viridula (L.), Acrosternum hilare (Say), and Euschistus
      servus (Say). Several other species also were commonly collected. This is the
      first record of Mormidea lugens (F.) on soybean and E. quadrator Rolston, E.
      obscurus (Palisot), Holcostethus limbolarius (Stal), and Oebalus pugnax (F.) on
      cotton. Stink bugs began arriving in soybean when plant growth stages ranged from
      pod formation to full seed development. Peak numbers of these insects were found
      in soybean from the time of full-size seeds in the pods until early maturity. The
      bugs were first attracted to the earlier maturing cultivar (group V), where they
      remained until plants began to mature (R7). The pentatomids then moved to the
      later-maturing cultivar (group VII) as it reached full pod to full seed. Stink
      bugs began arriving in cotton from the time of the earliest flowers until after
      the first bolls formed. Peak numbers in cotton occurred during the time when all
      stages of developing bolls were present. Stink bug numbers were much greater in
      soybean than in cotton over all three seasons. This preference for soybean over
      cotton indicates the potential use of soybean as a trap crop for attracting stink
      bugs away from cotton. Additionally, the coordinated use of early- and late
      maturing soybean cultivars as a trap crop could minimize the area requiring
      insecticides, as well as the number of insecticide applications to cotton.

PMID- 10902319
TI  - Delayed maturity associated with southern green stink bug (Heteroptera:
      Pentatomidae) injury at various soybean phenological stages.
AB  - Delayed maturity in soybean, Glycine max (L.) Merr., occurred in response to
      infestation by southern green stink bug, Nezara viridula (L.), in 4 yr of field
      studies. Maturity delays followed stink bug infestation that occurred only during
      the pod set and filling stages (R3-R5.5), and infestations at R3-4 and R5
      resulted in delayed maturity more consistently than did infestation at R5.5.
      Infestation levels of six stink bugs per 0.3 m of row for 7-14 d generally were
      required to delay soybean maturity. The greatest impact on seed yield and quality
      parameters followed stink bug infestations that occurred during R3-R5.5, which
      corresponded closely with the periods of infestation that resulted in delayed
      maturity. If both delayed maturity and yield reduction are considered, the pod
      elongation through late pod filling stages were most critical for protecting
      soybeans from southern green stink bugs.

PMID- 10902320
TI  - Laboratory and field evaluations of two Bacillus thuringiensis formulations,
      Novodor and Raven, for control of cottonwood leaf beetle (Coleoptera:
      Chrysomelidae).
AB  - Laboratory and field experiments were conducted to determine the efficacy of two
      Bacillus thuringiensis Berliner formulations, Novodor and Raven, for controlling
      cottonwood leaf beetle, Chrysomela scripta F. (Coleoptera: Chrysomelidae). In
      laboratory bioassays, larvae or adults were added to petri dishes containing
      Populus x euramericana Guinier 'Eugenei' foliage that had been treated with
      distilled water (control) or one of the commercial Bt formulations at either high
      or low label rates. Survival was recorded on a 24-h basis, and leaf area consumed
      was measured at the conclusion of all trials. Significant differences from the
      control in mortality and leaf area consumption resulted in the Novodor and Raven
      treatments for all life stages tested; however, adults were better able to
      withstand the effects of B. thuringiensis toxins than were the immatures. Early-
      and late instar C. scripta populations were monitored in the field (1998 and
      1999) after treatment with either water or various concentrations of one of the
      commercial Bt formulations. Significant mortality resulted with all
      concentrations and for all life stages tested compared with the control (tap
      water). The commercial formulations also were tested under plantation conditions
      as part of a long-term defoliation study. Both Novodor and Raven reduced
      cottonwood leaf beetle defoliation damage after a single application, giving high
      efficacy for control of cottonwood leaf beetle under the conditions and
      concentrations evaluated.

PMID- 10902321
TI  - Perimeter trapping strategy to reduce Mediterranean fruit fly (Diptera:
      Tephritidae) damage on different host species in Israel.
AB  - To evaluate the perimeter trapping strategy as a control method, field tests were
      conducted in three different host species of the Mediterranean fruit fly,
      Ceratitis capitata (Wiedemann), in Israel. Dry traps baited with a three
      component food-based synthetic attractant that were hung in the peripheral rows
      of a plum, a pear, and a persimmon orchard, caught female C. capitata (up to
      20.1, 1.4, and 4.1 female C. capitata per trap per day, respectively). Fruit
      damage, estimated at harvest, indicated a negligible percentage for the plum
      orchard (< 1%), 3% for the persimmon orchard (compared with 9% at an untreated
      neighboring plot), and no damaged fruit in the pear orchard. Finally, dissections
      of female C. capitata caught in dry traps on different host plant species
      indicate that a high percentage (range, 84-100%) contained mature eggs. The
      attraction of mature females to the dry traps might explain the successful
      results. Future research, to determine precisely how many traps should be placed
      and how frequently they should be serviced, is necessary before applying this
      strategy on a commercial basis.

PMID- 10902322
TI  - Effect of silver reflective mulch and a summer squash trap crop on densities of
      immature Bemisia argentifolii (Homoptera: Aleyrodidae) on organic bean.
AB  - Polyethylene mulch with a reflective silver stripe and a yellow summer squash,
      Cucurbita pepo L., trap crop were tested alone and in combination as tactics to
      reduce densities of Bemisia argentifolii Bellows & Perring eggs and nymphs, and
      incidence of bean golden mosaic geminivirus on snap bean, Phaseolus vulgaris L.
      Egg densities were consistently higher on squash than on bean, but egg densities
      and virus incidence were not lower on bean grown with squash than on bean grown
      in monoculture. Silver reflective mulch reduced egg densities compared with bean
      grown on bare ground during the first week after crop emergence for 2 of the 3 yr
      that the study was conducted. However, egg suppression by silver mulch was not
      enhanced by the presence of a squash trap crop when both tactics were combined.
      The obstacles to suppressing B. argentifolii through the use of trap crops are
      discussed.

PMID- 10902323
TI  - Effects of biorational pesticides on four coccinellid species (Coleoptera:
      Coccinellidae) having potential as biological control agents in interiorscapes.
AB  - The direct toxicity of insecticidal soap, horticultural oil, Azatin, an extract
      from the Neem tree containing azadiractin, and BotainiGard, a commercial
      formulation of the entomopathogenic fungus Beauveria bassiana, was assessed on
      adults of four species of coccinellids--Hippodamia convergens (Guerin-Meneville),
      Coleomegilla maculata (DeGeer), Harmonia axyridis Pallas, and Cryptolaemus
      montrouzieri Mulsant. All biorationals caused less mortality than a conventional
      pesticide, carbaryl (Sevin). Horticultural oil (Sunspray ultrafine oil)
      consistently had no effect on beetle survivorship. Insecticidal soap (M-Pede)
      significantly reduced survival in all replicates for C. maculata and in at least
      one of the three replicates for the other three coccinellid species. Beauveria
      bassiana (BotaniGard) significantly reduced survival of C. montrouzieri at 72 h
      after spray in all three replicates. Azatin reduced survivorship in only one
      species, C. maculata, in only one of the three replicates.

PMID- 10902324
TI  - Particle films for suppression of the codling moth (Lepidoptera: Tortricidae) in
      apple and pear orchards.
AB  - Studies were conducted in 1997 and 1998 to evaluate the effects of three particle
      film formulations consisting of kaolin and adjuvants on neonate larvae,
      ovipositing adult females, and eggs of the codling moth, Cydia pomonella (L.).
      Neonate larval walking speed, fruit discovery rate, and fruit penetration rate on
      apple host plants coated with particle films were significantly lower than on
      host plants without particle films in laboratory assays. Females oviposited less
      on host plants covered with a particle film residue than on untreated plants in
      laboratory choice and no-choice tests. Hatch rate of codling moth neonate larvae
      was unaffected by particle films sprayed on host plants either before or after
      oviposition. Fruit infestation rates were significantly reduced on particle film
      treated trees compared with untreated trees for both first- and second-generation
      codling moth in field trials in both apple and pear orchards. Particle films
      appear to be a promising supplemental control approach for codling moth in
      orchards where moth density is high, and may represent a stand-alone method where
      moth densities are lower.

PMID- 10902325
TI  - Effects of a kaolin-based particle film on obliquebanded leafroller (Lepidoptera:
      Tortricidae).
AB  - Studies were conducted in 1997 to evaluate the effects of the kaolin-based
      particle film formulation M96-018 on adults, eggs, and larvae of the
      obliquebanded leafroller, Choristoneura rosaceana (Harris). Particle film
      treatments significantly reduced female longevity, mating success, and number of
      egg masses oviposited compared with moths on untreated apple leaves in sleeve
      cage and screen-cage tests. No differences in mating success or oviposition were
      caused by the application rates and coverage density of M96-018 on foliage.
      Females avoided ovipositing on particle film-treated leaves in choice tests.
      Larval hatch was not affected by topical application or residual exposure to M96
      018. Larval weight gain and pupal weight were significantly reduced and larval
      mortality increased in no-choice feeding tests with M96-018. In choice tests,
      larvae preferred to feed on untreated leaf surfaces. The negative effects on
      larval development and survivorship on M96-018-treated foliage did not differ
      across a fourfold difference in spray application rate. A significant reduction
      in the number of infested shoots was found in orchard trials when M96-018 was
      applied before bud break in late March compared with untreated trees. No
      reductions in larval densities were found compared with an untreated control
      following prebloom and postbloom applications.

PMID- 10902326
TI  - Population dynamics of Bemisia argentifolii (Homoptera: Aleyrodidae) on spring
      collard and relationship to yield in the lower Rio Grande Valley of Texas.
AB  - Seasonal population dynamics of the silverleaf whitefly, Bemisia argentifolii
      Bellows & Perring [formerly known as the sweetpotato whitefly, B. tabaci
      (Gennadius) Biotype "B"], was investigated on collard (Brassica oleracea L.
      variety acephala) during spring 1998 and 1999 in the Lower Rio Grande Valley of
      Texas. Yield loss caused by whitefly was determined by using insecticides to
      suppress whitefly populations to a low level. Although B. argentifolii
      populations of adults and immatures fluctuated greatly from April to June during
      the two seasons, the relative values were similar. Adult whiteflies first
      appeared on the plants in early April, increased rapidly within the month, peaked
      in May, and declined at the end of the season in early or mid-June. Whitefly eggs
      appeared on plants soon after adults were found, but high numbers of eggs were
      observed on foliage until late May 1998 and mid- and late May 1999. Nymphs and
      pupae increased slowly before June 1998 and increased early in May 1999. Whitefly
      population levels appeared to be positively associated with the availability and
      the growth of host plants until plant maturation, afterward being negatively
      related with plant quality in the late season. Temperature, rainfall, and natural
      enemies were not key factors in regulating population dynamics during the two
      seasons. Collard plants with heavy infestations of whiteflies were unmarketable
      because of the damage caused by honeydew and sooty mold on the foliage.
      Application of a combination of fenpropathrin (Danitol) and acephate (Orthene)
      not only significantly reduced the whitefly infestation levels but also reduced
      plant foliar damage, resulting in marketable foliage with six to seven times
      greater yield and higher quality compared with the untreated plants.

PMID- 10902327
TI  - Dogwood borer (Lepidoptera: Sesiidae) infestation of horned oak galls.
AB  - Pin oak, Quercus palustris Muenchhausen, is the primary host for the gall wasp
      Callirhytis cornigera (Osten Sacken). Woody stem galls formed by C. cornigera may
      be infested by the dogwood borer, Synanthedon scitula (Harris), an important pest
      of flowering dogwood, Cornus florida L. Previous research has shown that S.
      scitula has a bimodal seasonal flight pattern, with peaks in late spring and
      midsummer. We tested the hypothesis that moths emerging from dogwoods largely
      account for the first flight pulse, whereas emergence from stem galls contributes
      disproportionately to the second pulse. Seasonal flight activity of S. scitula
      was monitored with pheromone traps baited with Z,Z-3,13-octadecadien-1-ol
      acetate. Traps were hung near plantings of dogwoods in suburban landscapes or
      near heavily galled pin oaks. Borer emergence from dogwood was monitored by
      sampling infested trees for pupal exuviae, and from galls that were collected and
      held in outdoor rearing cages. The impact of S. scitula on C. cornigera larvae
      was assessed by weighing, measuring, and dissecting galls. Flight activity of S.
      scitula began on 5 May and ended on 13 October 1999, with peaks in late May and
      in late July to early August. The flight pattern was similar for the two types of
      trapping sites, and moths emerged from both hosts during both flight periods.
      Proportionately more moths emerged from dogwoods during the first flight pulse
      than during the second, but emergence from galls was nearly evenly divided
      between the two flight peaks. We therefore reject the hypothesis that emergence
      of borers from galls contributes disproportionately to the second flight period.
      Approximately 12-15% of stem galls (2-3 yr old) contained S. scitula larvae.
      Feeding and tunneling by borers contributed to gall desiccation and reduced horn
      development, but rarely killed C. cornigera larvae. This study has implications
      for management of S. scitula because borers emerging from horned oak galls may
      represent a threat to dogwood.

PMID- 10902328
TI  - Effect of insecticides on the diamondback moth (Lepidoptera: Plutellidae) and its
      parasitoid Diadegma insulare (Hymenoptera: Ichneumonidae).
AB  - Studies were conducted to evaluate the toxicity of insecticides to adult Diadegma
      insulare (Cresson) and its host the diamondback moth, Plutella xylostella (L.).
      Leaf-dip and direct-dip bioassays for diamondback moth larvae and residual
      bioassays for adults of diamondback moth and D. insulare were used to assess
      mortalities. Larval mortalities at field rates were significantly higher with
      carbaryl, permethrin, spinosad, and tebufenozide when compared with Bacillus
      thuringiensis, or imidacloprid in the larval-dip bioassay 72 h after treatment.
      In the leaf-dip and residual bioassays, both permethrin and spinosad caused 100%
      mortalities to diamondback moth larvae and adults, respectively, 72 h after
      treatment. Of all the materials tested, only B. thuringiensis and tebufenozide
      were not toxic to D. insulare 24 h after treatment. Spinosad was not toxic to D.
      insulare 30 min after treatment. However, 100% mortality was observed 8 h after
      treatment.

PMID- 10902329
TI  - Comparison of pheromone-mediated mating disruption and conventional insecticides
      for management of tufted apple bud moth (Lepidoptera: Tortricidae).
AB  - Large-plot studies were used to compare pheromone-mediated mating disruption and
      conventional insecticide applications for management of tufted apple bud moth,
      Platynota idaeusalis (Walker), in North Carolina in 1993 and 1994. Pheromone trap
      catches were reduced in mating disruption blocks, and traps placed in the lower
      stratum of the canopy had a higher level of trap capture reduction compared with
      traps placed in the upper stratum. First-generation tufted apple bud moth
      exposure to either pheromones for mating disruption or insecticides affected
      second generation pheromone trap catches in the lower and upper canopy. More
      second generation male moths were caught in pheromone traps placed in the upper
      compared with the lower canopy in blocks treated with pheromones for mating
      disruption during the first generation, whereas the opposite was true in blocks
      treated with insecticides during the first generation. Despite reduced trap
      catches in pheromone-treated blocks, egg mass densities were not reduced in these
      blocks compared with insecticide-treated blocks. Furthermore, fruit damage was
      not significantly different between mating disruption blocks and conventionally
      treated blocks in orchards with relatively low populations of tufted apple bud
      moth, but damage was greater in mating disruption blocks in orchards with higher
      moth densities.

PMID- 10902330
TI  - Evaluation of border sprays for managing the codling moth (Tortricidae:
      Lepidoptera) and the apple maggot (Tephritidae: Diptera) in Ontario apple
      orchards.
AB  - The efficacy of two insecticide control programs for managing the codling moth,
      Cydia pomonella (L.), and the apple maggot, Rhagoletis pomonella (Walsh), were
      compared in the Georgian Bay, London, Niagara, and Quinte apple production areas
      of Ontario during 1995, 1996, and 1997. In the border spray program, an initial
      cover spray of organophosphorus insecticide was applied to eradicate codling
      moths that may have colonized a test plot during the previous growing season.
      Subsequent sprays were applied only to a four-tree-wide zone (approximately 20
      wide) around the perimeter of the plot to control immigrating codling moths or
      apple maggots. In the cover spray program, all sprays of organophosphorus
      insecticide were applied to the entire plot. Apple maggot injury was
      significantly greater in border spray program plots than in cover spray program
      plots only during 1995 in the London production area. There was no significant
      difference in codling moth injury between border spray and cover spray plots in
      the four production areas during the three-year study. The elimination of cover
      sprays from border spray plots during July and August may have left the apple
      crop more susceptible to damage by second generation larvae of the obliquebanded
      leafroller, Choristoneura rosaceana (Harris), in the London production area
      during 1995. There was a trend of increasing codling moth injury from 1995 to
      1997 in two border spray plots, and apple maggot injury was detected in these
      plots during the third year of the study.

PMID- 10902331
TI  - Impact of insecticides and surfactant on lettuce physiology and yield.
AB  - Insecticides are used extensively on lettuce, Lactuca sativa L., grown in
      southwestern Arizona because of heavy insect pressure that can potentially reduce
      lettuce productivity. Multiple sprays are made per season to manage these insects
      in lettuce. One of the major concerns related to extensive insecticide
      applications in lettuce is the potential subtle impact of insecticides that may
      reduce lettuce photosynthesis and yield. We conducted field and greenhouse
      experiments to examine the impact of multiple insecticides and surfactant spray
      applications on lettuce photosynthesis and yield. Lettuce was planted in the
      field in 1998, insecticides and surfactant were applied, and lettuce gas-exchange
      and dry weights were determined. Treatments were arranged in a split-plot
      consisting of insecticides as main plot and surfactant as subplot treatments in a
      randomized complete block design with four replications. Photosynthetic rates of
      lettuce were significantly reduced by endosulfan, methomyl, acephate, and
      surfactant at seedling stage 4 h and 2 d after the spray application was made.
      However, the reduction in lettuce photosynthesis by these insecticides and
      surfactant was only transient, and lettuce photosynthesis recovered 5 d after the
      spray application was made. Photosynthetic rates were not altered by zeta
      cypermethrin, emamectin benzoate, and spinosad at the seedling stage.
      Insecticides or surfactant (Kinetic, a nonionic surfactant) did not significantly
      affect lettuce photosynthesis after rosette formation. In addition, lettuce dry
      weight was not significantly altered. These studies suggest that lettuce
      photosynthesis may be susceptible to some insecticides at the seedling stage.
      Consequently, we found that biorational insecticides, introduced to manage insect
      pests in lettuce, have no influence on lettuce physiology at the seedling stage,
      unlike the chlorinated hydrocarbons, organophosphates, or carbamates tested in
      this study. In a greenhouse study, we found that lettuce photosynthesis and yield
      were not altered by Bacillus thuringiensis application. Our results indicate that
      B. thuringiensis and the newer insecticides, particularly biorationals, can be
      used to manage lettuce insect pests without significantly altering lettuce gas
      exchange and yield.

PMID- 10902332
TI  - Grape cane gallmaker (Coleoptera: Curculionidae) and its impact on cultivated
      grapes.
AB  - The grape cane gallmaker, Ampeloglypter sesostris (Leconte), is a native weevil
      that infests new shoots of wild and cultivated grapes (Vitis spp.). Females
      oviposit on the tender portions of new shoots, producing a reddish gall that can
      expand the shoot to twice its normal diameter. These galls can be quite numerous
      in eastern vineyards, and their effects are unknown. We studied the spatial
      distribution of grape cane gallmaker and its impact on berry size, sugar content,
      and nutrient and mineral uptake. We observed spatial trends in grape cane
      gallmaker distribution in vineyards adjacent to woodland margins, with the trend
      emanating from the woodline. In vineyards without woodland margins, there was
      little spatial dependency in grape cane gallmaker distribution in individual
      years. However, grape cane gallmaker density on a single vine was spatially cross
      correlated between 2 yr. The presence of galls did not significantly affect berry
      quality, or the uptake of nutrients and minerals, and we conclude that grape cane
      gallmaker does not negatively impact berry quality or mature vine vigor.

PMID- 10902333
TI  - Comparison of greenhouse screening materials for excluding whitefly (Homoptera:
      Aleyrodidae) and thrips (Thysanoptera: Thripidae).
AB  - Twenty-eight greenhouse screening materials, with predetermined airflow
      resistance values, were evaluated for exclusion of the silverleaf whitefly
      Bemisia argentifolii Perring & Bellows and thrips from a mixed-species
      population. Screens differed in exclusion efficacy, expressed as a percentage of
      the fiberglass window screen control and at an approach velocity of 92 m/min,
      from -35 to 94% for silverleaf whitefly and from -13 to 95% for thrips. Seventeen
      screens excluded more silverleaf whitefly than did the window screen control,
      whereas only seven excluded more thrips. One material differentially excluded
      whitefly over thrips; many more differentially excluded thrips over whitefly.
      Airflow resistance, indicative of mesh hole size, did not necessarily correspond
      with degree of exclusion. Not all materials characterized as highly resistant to
      airflow provided significant exclusion. Exclusion of both types of pests was
      attained with several moderate- and one low-resistance screen. Another low
      resistance screen excluded silverleaf whitefly only.

PMID- 10902334
TI  - Impact of western corn rootworm (Coleoptera: Chrysomelidae) on sweet corn and
      evaluation of insecticidal and cultural control options.
AB  - The western corn rootworm, Diabrotica virgifera virgifera LeConte, is an
      important pest of corn, Zea mays L., causing yield losses from root damage, plant
      lodging, and silk feeding. Because little is known about its impact on sweet
      corn, we conducted research to evaluate the combined effects of insecticide,
      planting date, and cultivar on root damage, plant lodging, and yield in central
      New York sweet corn. We also examined the influence of planting date and cultivar
      on the emergence of adult western corn rootworms. The research was conducted in
      1994 and again in 1995 by using a split-split plot experimental design with
      insecticide as main plot, planting date as subplot, and cultivar as sub-subplot.
      The effect of cultivar on beetle emergence was not significant. Root damage was
      not correlated with adult emergence in 1994 but was positively correlated in
      1995. In 1994, there was no interaction of the main factors, and all factors had
      a significant impact on root damage. In 1995 there was an interaction of
      insecticide and planting date, and of cultivar and planting date. Generally, root
      damage was reduced by insecticide and later planting. Plant lodging was affected
      by the interaction of insecticide and planting date, and the interaction of
      cultivar and planting date, for both years of the study. As with root damage,
      lodging was reduced with insecticide treatment and later planting but also was
      dependent on cultivar. In 1994 and especially in 1995, silk clipping by adult
      western corn rootworms precluded much inference about how yield was influenced by
      larval feeding damage on roots. The number of emerging western corn rootworm
      adults was lower and later in later plantings.

PMID- 10902335
TI  - Imidacloprid applications by subirrigation for control of silverleaf whitefly
      (Homoptera: Aleyrodidae) on poinsettia.
AB  - The objective of this study was to determine whether silverleaf whiteflies,
      Bemisia argentifolii Bellows & Perring, on poinsettia, Euphorbia pulcherrima
      Willdenow ex Klotsch, can be controlled with imidacloprid applied by
      subirrigation. Different amounts of imidacloprid uptake by the growing medium
      were obtained by not watering the subirrigated plants for 0, 1, 2, or 4 d before
      the imidacloprid application. These treatments resulted in absorption of 12-175
      ml of imidacloprid solution by the growing medium. These treatments were compared
      with untreated control plants and plants that were treated with a standard drench
      application (100 ml) to the top of the growing medium. All imidacloprid
      treatments resulted in a significant decrease in both the survival of adult
      whiteflies and number of immature whiteflies on the plants. Subirrigation
      treatments resulted in better control of adult and immature whiteflies than
      drench application. Withholding water for 2 or 4 d before the imidacloprid
      application by subirrigation improved control of immature whiteflies. This
      indicates that the application of imidacloprid to poinsettia by subirrigation is
      a practical and efficient method to control silverleaf whiteflies.

PMID- 10902336
TI  - Comparison of pheromone application rates, point source densities, and dispensing
      methods for mating disruption of tufted apple bud moth (Lepidoptera:
      Tortricidae).
AB  - Small-plot (approximately 0.1 ha) studies were used to evaluate different
      pheromone dispensing systems, application rates, and point-source densities for
      mating disruption of the tufted apple bud moth, Platynota idaeusalis (Walker).
      Using polyvinyl chloride spirals impregnated with tufted apple bud moth pheromone
      (1:1 ratio of E11-tetradecenyl alcohol/E11-tetradecenyl acetate), pheromone rates
      of > or = 1,482 spirals per hectare (74.1 g pheromone per hectare) were superior
      to a rate of 988 spirals per hectare (49.4 g pheromone per hectare) in decreasing
      male response to pheromone traps in 1995, whereas no differences were detected
      among rates of 988, 1,482 and 1,975 spirals per hectare in 1996. Within a range
      of 370-988 pheromone dispensers per hectare, point source densities were equally
      effective in suppressing male response to pheromone traps. Pheromone-impregnated
      paraffin disks were equally effective at inhibiting male response to pheromone
      traps compared with polyvinyl chloride spirals. However, a paraffin emulsion
      formulation of pheromone applied with a hand-held grease gun provided longer
      residual communication disruption effects than polyvinyl chloride spirals.
      Dilution of paraffin emulsion pheromone formulations in water for application
      with a backpack sprayer and airblast sprayer rendered them ineffective in
      reducing male response to pheromone traps. The releases of pheromone from
      polyvinyl chloride spirals and paraffin disks aged in the field were described by
      a linear and negative logarithmic curve, respectively, indicating that dispenser
      life time should be longer for spirals. The ratio of acetate to alcohol
      components of pheromone released from spirals increased over time, whereas the
      release ratio remained more constant for paraffin disks. This suggests that the
      disruption efficacy of spirals may be prematurely reduced because of imbalance of
      the released components.

PMID- 10902337
TI  - Reflective and black mulch increase yield in pumpkins under virus disease
      pressure.
AB  - Experiments were conducted over a 4-yr period that examined the effect
      reflective, black, and no-mulch had on aphid populations, incidence of virus
      infected pumpkin plants, and yield of pumpkin. Three different planting dates and
      their effect on viral infection and yield were also investigated. The use of
      reflective mulches significantly reduced the number of alates landing in these
      rows compared with black- or no-mulch rows. The reduction in aphid numbers
      resulted in a reduction in the percent of plants infected with virus.
      Approximately 10 times more plants were infected with virus in the black and no
      mulch plots than in the reflective mulch plots in mid- to late July. However, by
      the end of August, all treatments had near 100% of plants infected with virus.
      This delay in viral infection in reflective mulch plots resulted in a 45 and 120%
      increase in pumpkin yield compared with black mulch and no-mulch plots,
      respectively. First plantings always had greater yields than later plantings. The
      interaction between mulch type and planting time was significant. Reflective
      mulches increased yields overall, but significantly increased yields compared
      with black or no-mulch in second and third plantings. The use of reflective mulch
      combined with timely planting is a cost effective way of delaying virus problems
      and increasing pumpkin yields in midwestern United States.

PMID- 10902338
TI  - Sequential sampling plans for the hairy chinch bug (Hemiptera: Lygaeidae).
AB  - Two sequential sampling plans were developed to produce tools to reduce the use
      of pesticides for the control of the hairy chinch bug, Blissus leucopterus hirtus
      Montandon, on turfgrass lawns in the cool-humid region of Quebec, Canada. A first
      plan based on Wald's method was shown to be too conservative in a validation
      conducted on infested lawns. The second plan developed using Iwao's method
      yielded good results. The difference between the two plans may have occurred
      because no common k could be found for the negative binomial functions describing
      chinch bug distribution on lawns, thereby violating an essential assumption of
      Wald's approach. Application of the Iwao plan, which is based on visual sampling
      of 0.1-m2 quadrats, requires approximately 20 min when lawn evaluation is
      conducted by a single person. Estimation of the occurrence of chinch bug
      infestations (28% infested lawns in the regions of Montreal and Quebec cities),
      and results from validation of the Iwao plan on infested lawns, indicate that the
      error rates alpha and beta of the plan are lower than an upper limit of 0.05 and
      0.14, respectively. The adequate precision and practicality of this plan suggest
      that it could become an essential tool for management of turfgrass lawns in
      regions where the hairy chinch bug completes less than two generations per
      growing season.

PMID- 10902339
TI  - Jasmonic acid induced resistance in grapevines to a root and leaf feeder.
AB  - We investigated the effects of induced resistance to the folivore Pacific spider
      mite, Tetranychus pacificus McGregor (Acari: Tetranychidae), as well as the root
      feeding grape phylloxera Daktulosphaira vitifoliae (Fitch) (Homoptera:
      Phylloxeridae) in grapevines using exogenous applications of the natural plant
      inducer, jasmonic acid. Foliar jasmonic acid application at concentrations that
      caused no phytotoxicity significantly reduced the performance of both herbivores.
      There were less than half as many eggs produced by spider mites feeding on the
      induced leaves compared with control grapevine leaves. Induction reduced the
      numbers of phylloxera eggs and nymphal instars by approximately threefold and
      twofold, respectively, on induced compared with control grapevine roots. The
      negative demographic effects of jasmonic acid application appeared to be caused
      by changes in fecundity for the Pacific spider mite, and possibly changes in
      development rate and fecundity for grape phylloxera.

PMID- 10902340
TI  - Field infestation of rambutan fruits by internal-feeding pests in Hawaii.
AB  - More than 47,000 mature fruits of nine different varieties of rambutan (Nephelium
      lappaceum L.) were harvested from orchards in Hawaii to assess natural levels of
      infestation by tephritid fruit flies and other internal feeding pests.
      Additionally, harvested, mature fruits of seven different rambutan varieties were
      artificially infested with eggs or first-instars of Mediterranean fruit fly,
      Ceratitis capitata (Wiedemann), or oriental fruit fly, Bactrocera dorsalis
      (Hendel) (Diptera: Tephritidae) to assess host suitability. When all varieties
      were combined over two field seasons of sampling, fruit infestation rates were
      0.021% for oriental fruit fly, 0.097% for Cryptophlebia spp. (Lepidoptera:
      Tortricidae), and 0.85% for pyralids (Lepidoptera). Species of Cryptophlebia
      included both C. illepida (Butler), the native Hawaiian species, and C.
      ombrodelta (Lower), an introduced species from Australia. Cryptophlebia spp. had
      not previously been known to attack rambutan. The pyralid infestation was mainly
      attributable to Cryptoblabes gnidiella (Milliere), a species also not previously
      recorded on rambutan in Hawaii. Overall infestation rate for other moths in the
      families Blastobasidae, Gracillariidae, Tineidae, and Tortricidae was 0.061%. In
      artificially infested fruits, both species of fruit fly showed moderately high
      survivorship for all varieties tested. Because rambutan has such low rates of
      infestation by oriental fruit fly and Cryptophlebia spp., the two primary
      internal-feeding regulatory pests of rambutan in Hawaii, it may be amenable to
      the alternative treatment efficacy approach to postharvest quarantine treatment.

PMID- 10902341
TI  - Effect of irrigation on the efficacy of insecticides for controlling two species
      of mole crickets (Orthoptera: Gryllotalpidae) on golf courses.
AB  - Effects of irrigation regimen, quantity, and timing on the efficacy of three
      insecticides for controlling nymphs of the southern mole cricket, Scapteriscus
      borellii Giglio-Tos, and the tawny mole cricket, Scapteriscus vicinus Scudder,
      were studied on golf courses in 1997, 1998, and 1999. Two irrigation regimen
      tests using two rates of bifenthrin and lambda-cyhalothrin produced inconclusive
      results. Mole cricket damage ratings after the applications of bifenthrin (60 g
      [AI]/ha) and lambda-cyhalothrin (76 g [AI]/ha) were not significantly different
      among the four irrigation regimens (non-irrigation, irrigation before treatment,
      irrigation after treatment, and irrigation before and after treatment). Mole
      cricket damage rating after the application of bifenthrin (120 g [AI]/ha) under
      irrigation before and after irrigation was significantly better than those under
      other irrigation regimens at 14 and 21 d after treatment (DAT). Different
      irrigation quantity and irrigation timing (after insecticide treatment) did not
      significantly affect the performance of imidacloprid (434 g [AI]/ha) in the 1998
      tests. However, the results from the 1999 test indicated that mole cricket damage
      ratings from the imidacloprid-treated plots were significantly different between
      2 and 0.5 cm irrigation water after treatment at 21 and 28 DAT. Application of
      bifenthrin at a rate of 120 g (AI)/ha with 0.5 cm of irrigation water after
      treatment resulted in significantly lower mole cricket damage ratings than those
      of 1.0 and 2.0 cm of irrigation water after treatment at 30 DAT only in the 1998
      test. Bifenthrin with irrigation at 1 h after insecticide treatment provided
      better mole cricket control than that of irrigation at 5 min after treatment at
      30 DAT only in the 1998 test. Mole cricket damage ratings after application of
      bifenthrin were not significantly different between either irrigation quantity
      treatment or irrigation timing treatment in the 1999 tests. Possible effects of
      application timing, environmental conditions, irrigation practice, and
      insecticide physical properties on the results are discussed.

PMID- 10902343
TI  - Use of fecal extract trails to enhance trap catch in German cockroach
      (Dictyoptera: Blattellidae) monitoring stations.
AB  - An aqueous extract of German cockroach, Blattella germanica (L.), fecal material
      was evaluated for inducing trail-following behavior in German cockroaches. In
      arena tests the fecal extract was found to stimulate trail following in 74% of
      adult male cockroaches. Significantly fewer cockroaches (22%) followed water
      treated (control) trails. Residual activity of the fecal extract trails was
      evaluated by bioassay after the trails had been stored in the refrigerator or in
      the open air. Although trails stored in the refrigerator showed no decline in
      activity after 14 d, those stored in the open air declined significantly after 3
      d, inducing only 40% of adult male cockroaches to follow the trail. After 7 d the
      activity of trails stored in the open air was further reduced to 23%. The ability
      of fecal-extract trails to influence trap catch in monitoring stations was
      determined by bioassay. Paper trails treated with fecal extract or water were
      positioned between cockroach harborages and monitoring stations inside 122-cm2
      arenas. The presence of the fecal extract-treated trails significantly enhanced
      trap catch. Mean catch in the traps with fecal extract trails was 28 cockroaches
      compared with a mean of 11 cockroaches in the control traps. The trap catch
      ratios of adults to nymphs in the treated and control treatments were not
      significantly different.

PMID- 10902342
TI  - Oral toxicity of abamectin, boric acid, fipronil, and hydramethylnon to
      laboratory colonies of Argentine ants (Hymenoptera: Formicidae).
AB  - Comprehensive laboratory baiting studies with the 4 insecticides abamectin, boric
      acid, fipronil, and hydramethylnon were conducted against Argentine ant,
      Linepithema humile (Mayr). Serial dilutions of each insecticide prepared in a 25%
      sucrose solution were provided for 24 h or 14 d to groups of workers and queens.
      Sucrose-water baits containing 1 x 10(-5)% fipronil and 0.1% hydramethylnon
      provided complete mortality of L. humile workers baited for 24 h. Baits
      containing 1 x 10(-4) and 1 x 10(-5)% fipronil provided 100% kill of queens. In
      the continuous baiting, 0.5% boric acid, 1 x 10(-6)% fipronil, and 0.025%
      hydramethylnon provided 100% mortality of workers. The queens and workers
      provided baits containing 1 x 10(-5)% fipronil and 0.5% boric acid all died
      within 14 d. Low concentrations of fipronil and boric acid in sucrose may be
      promising candidates for Argentine ant control.

PMID- 10902344
TI  - Kinetics of uptake, clearance, transfer, and metabolism of hexaflumuron by
      eastern subterranean termites (Isoptera: Rhinotermitidae).
AB  - The rates of uptake, clearance, insect-to-insect transfer, and metabolism of
      [14C] hexaflumuron [N-(((3,5-dichloro-4-(1,1,2,2-tetrafluroethoxy)phenyl)-
      amino)carbonyl)-2,6-diflurobenzamide] were measured in eastern subterranean
      termite workers, Reticulitermes flavipes (Kollar), fed cellulose diets containing
      either 0.1 or 0.5% (wt:wt) hexaflumuron. The rate of uptake, level of maximum
      uptake, and amount of insect-to-insect transfer were concentration dependent. The
      clearance rate constant for hexaflumuron was independent of concentration, with a
      mean value of 3.2 x 10(-3)/h. This corresponds to a mean half-life for
      hexaflumuron inside termites of 9 d. No evidence of metabolism of hexaflumuron to
      additional products was detected when extracting and examining the radioactivity
      contained in the fecal and regurgitated material within the termite holding
      apparatus 40 d after exposure to the chemical. Hexaflumuron was efficiently
      transferred from treated to untreated termites, through trophallaxis, resulting
      in spread of the toxicant throughout the insect population. The combination of
      uptake and efficient transfer of hexaflumuron between treated and untreated
      termites ensures broad distribution of the material even to insects not directly
      exposed to the toxicant. The distribution of hexaflumuron by termite workers,
      along with their minimal ability to metabolize the compound to other metabolites,
      and their slow ability to clear the material from the termite population results
      in death of the entire group of termites contained within the holding apparatus.

PMID- 10902345
TI  - Rapid antibody-based field test to distinguish between Helicoverpa armigera
      (Lepidoptera: Noctuidae) and Helicoverpa punctigera (Lepidoptera: Noctuidae).
AB  - Helicoverpa armigera (Hubner) and Helicoverpa punctigera (Wallengren) are the two
      most important insect pests of cotton production in Australia and require
      application of insecticides to control them. H. armigera has developed resistance
      to several insecticides but H. punctigera has not. Cost-effective management of
      insecticide resistance requires that growers be able to determine the proportion
      of H. armigera eggs or young larvae present on their crop before applying
      insecticides. This is impossible visually. We generated two monoclonal antibodies
      that reacted with the insect protein "lipophorin" and were capable of
      discriminating individuals of the two species at all life-stages. The antibodies
      were incorporated into a rapid test kit that was tested under field conditions
      over two growing seasons. Results obtained with the kit agreed closely with those
      obtained by rearing larvae through to second instar.

PMID- 10902346
TI  - Changes in midgut endopeptidase activity of Spodoptera frugiperda (Lepidoptera:
      Noctuidae) are responsible for adaptation to soybean proteinase inhibitors.
AB  - The development of transgenic maize plants expressing soybean proteinase
      inhibitors could reduce the economic damage of one of the major maize pests in
      Brazil, the fall armyworm, Spodoptera frugiperda (J.E. Smith, 1797). We examined
      the influence of soybean proteinase inhibitors on digestive enzyme properties and
      development of S. frugiperda larvae. The inhibition of trypsin and chymotrypsin
      activities in vitro by soybean proteinase inhibitors suggested that either Kunitz
      (SBTI) or Bowman-Birk (SBBI) would have a potential antimetabolic effect when
      ingested by insect larvae. However, chronic ingestion of semipurified soybean
      inhibitors did not result in a significant reduction of growth and development of
      fall armyworm. Therefore, digestive serine proteinase activities (trypsin and
      chymotrypsin) of fall armyworm larvae were characterized. The results suggest
      that S. frugiperda was able to physiologically adapt to dietary proteinase
      inhibitors by altering the complement of proteolytic enzymes in the insect
      midguts.

PMID- 10902347
TI  - Development of diagnostic concentrations for insecticide resistance monitoring in
      soybean looper (Lepidoptera: Noctuidae) larvae using an artificial diet overlay
      bioassay.
AB  - Diagnostic concentrations for several standard and experimental insecticides were
      determined for a laboratory reference strain of soybean looper, Pseudoplusia
      includens (Walker), using an insecticide diet overlay bioassay to evaluate the
      relative susceptibility of field (P) and F1 generations of four field-collected
      strains of third-, fourth-, and fifth-instar soybean loopers in 1996 and 1997.
      Diagnostic concentrations were defined as concentrations that killed 90-95% of
      the susceptible individuals and were 5 ppm for permethrin, 1,300 ppm for
      thiodicarb, 60 ppm for chlorfenapyr, 5 ppm for emamectin benzoate, and 60 ppm for
      spinosad. Field strains exhibited significantly greater percentage survival than
      the laboratory reference strain in the permethrin bioassays in 1996 and 1997 in
      both the P and F1 generation bioassays and in the thiodicarb bioassays in 1997.
      Larvae exposed to diagnostic concentrations of the experimental insecticides
      chlorfenapyr, emamectin benzoate, and spinosad usually did not exhibit
      significantly higher percentage survival than the reference strain.

PMID- 10902348
TI  - Comparison of two bioassay methods for determining deltamethrin resistance in
      German cockroaches (Blattodea: Blattellidae).
AB  - Susceptibility to deltamethrin of 10 strains of the German cockroach, Blattella
      germanica (L.), trapped in hotel kitchens in Singapore was determined. Two
      resistance detection bioassay methods (topical application and World Health
      Organization glass jar method) were compared. Resistance ratios based on 50%
      knockdown, obtained by comparison with the S strain, ranged from 17.7 to 4,235
      for topical application and from 2.2 to 22 for the glass jar method. A field
      strain, with consistently low resistance ratios (topical method = 17.7, glass jar
      method = 2.2), was identified as a potential field strain to be used as a
      baseline for comparison with other field strains. Resistance ratios for the other
      field strains obtained by comparison with the R5 strain ranged from 24.5 to 239
      for topical application and from 1.2 to 9.8 for the glass jar method. The results
      of our study demonstrate that deltamethrin-resistant German cockroaches are
      numerous in Singapore. Comparison between the two bioassay methods showed that
      there was significant correlation between KD50 and KT50 values. The glass jar
      method is similar to field situations but topical application is sensitive enough
      to define the magnitude of resistance. Differences between the two detection
      bioassays and the factors governing the choice of bioassay in monitoring
      resistance in German cockroaches are discussed.

PMID- 10902349
TI  - A genetic analysis of cyromazine resistance in Drosophila melanogaster (Diptera:
      Drosophilidae).
AB  - Flies resistant to the insect growth regulator cyromazine were selected in the F1
      generation from a cyromazine-susceptible strain of Drosophila melanogaster
      (Meigen) treated with ethyl methanesulfonate. Four resistant strains were
      isolated by screening with cyromazine at a concentration > LC100 of susceptibles.
      In each strain, resistance is conferred by a single gene mutation. Cyromazine
      resistance in two of the mutants (rst(1a)cyr1 and rst(1a)cyr2) localizes to map
      position 17 of the X chromosome. Evidence is presented that these mutations are
      alleles of the gene rst(1a)cyr. Cyromazine resistance in another of the mutants
      (Rst(1b)Cyr) is also X-linked, and localizes to map position 49 of the X
      chromosome. The location of the gene conferring cyromazine resistance in the
      other mutant (Rst(2b)Cyr) is map position 66 of chromosome II. This is possibly
      an allele of a previously characterized cyromazine resistance gene, Rst(2)Cyr.
      Dosage-mortality analyses demonstrate a low level of cyromazine resistance is
      conferred in all strains.

PMID- 10902351
TI  - Development of diagnostic concentrations for monitoring Bacillus thuringiensis
      resistance in European corn borer (Lepidoptera: Crambidae).
AB  - Two candidate diagnostic concentrations of the Cry1Ab and Cry1Ac toxins from
      Bacillus thuringiensis corresponding to the LC99 and EC99 (effective
      concentration that causes 99% growth inhibition) for European corn borer,
      Ostrinia nubilalis (Hubner), were determined based on previously obtained
      baseline data. Validation experiments using field-collected European corn borer
      populations from across North America showed that for Cry1Ab, a concentration
      corresponding to the upper limit of the 95% confidence interval of the LC99,
      produced mortality > 99% for all populations tested. However, for Cry1Ac,
      adjustments and further validation are probably necessary. Development of B.
      thuringiensis resistance monitoring programs that rely on diagnostic techniques
      are discussed.

PMID- 10902350
TI  - Evaluation of horn flies (Diptera: Muscidae) from a pyrethroid susceptible colony
      for general and permethrin esterase activities.
AB  - In this study we describe a nonradioactive single-fly microassay for permethrin
      hydrolysis. We used this assay with a microplate assay for general esterase
      activity to evaluate the permethrin hydrolyzing and general esterase activities
      of aging pyrethroid-susceptible male and female horn flies, Haematobia irritans
      (L.). We found substantial gender- and age-related differences regarding general
      esterase activity, permethrin sensitivity, and permethrin hydrolyzing activity
      within the colony. Extracts of female flies collected 48 h after receiving their
      first blood meal yielded significantly greater esterase activity than male
      extracts. Aging female flies were more tolerant of permethrin than were male
      flies. In addition, a positive correlation was found to exist between the general
      esterase activity of aging females and their ability to hydrolyze permethrin.

PMID- 10902352
TI  - Assessment of insecticide resistance after the outbreak of diamondback moth
      (Lepidoptera: Plutellidae) in California in 1997.
AB  - During an outbreak of the diamondback moth, Plutella xylostella (L.), in
      California in 1997, nine populations were collected from the major broccoli areas
      throughout the state. Populations were assayed for their susceptibility to
      currently used materials (Bacillus thuringiensis subsp. kurstaki, permethrin, and
      methomyl) and to newer materials that had not yet been commercially used in
      California (spinosad, emamectin benzoate, and chlorfenapyr). For the currently
      used insecticides, elevated levels of resistance were seen only with permethrin
      and seven of the nine populations had tolerance ratios (TR) of > 100. With the
      newer chemistries, TR values were all < 15. To compare potential cross-tolerance,
      TR values of the currently used insecticides were compared with TR values of the
      newer insecticides. There were significant relationships found between: methomyl
      and emamectin benzoate, methomyl and spinosad, and permethrin and spinosad.
      Further biochemical studies are needed to confirm the actual mechanisms that lead
      to these relationships and field tests are needed to determine what impact, if
      any, such TR levels would have on control in the field. These data indicate that
      resistance to at least one of the commonly used insecticides (permethrin) may
      have played a role in the outbreak during 1997. However, other factors may have
      been at least equally important. The winter of 1996-1997 was warmer than normal,
      and during the period from February through August of 1997 the amount of rainfall
      was < 50% of normal. Hot and dry conditions are known to be conducive to
      outbreaks of P. xylostella. These data add to an overall knowledge about the
      geographic variation of resistance in P. xylostella populations within the United
      States. They also serve as a baseline for monitoring changes in susceptibility to
      these newer insecticides and can also help explain the occurrence of outbreaks
      caused by factors other than insecticide resistance.

PMID- 10902353
TI  - Seed mixtures as a resistance management strategy for European corn borers
      (Lepidoptera: Crambidae) infesting transgenic corn expressing Cry1Ab protein.
AB  - Dispersal of neonate European corn borers, Ostrinia nubilalis (Hubner), in seed
      mixtures of transgenic corn expressing Cry1Ab protein (Bt+) and nontransgenic
      corn (Bt-) was evaluated in a 2-yr field study. The main objective was to
      determine if larval dispersal limits the effectiveness of seed mixtures as a
      resistance management strategy. Mixtures evaluated included (1) all Bt+ plants,
      (2) every fifth plant Bt- with remaining plants Bt+, (3) every fifth plant Bt+
      with remaining plants Bt-, and (4) all Bt- plants. The transformation events MON
      802 (B73 BC1F2 x Mol7) and MON 810 (B73 BC1F1 x Mo17), which express the Cry1Ab
      endotoxin isolated from Bacillus thuringiensis subsp. kurstaki, were used as the
      sources of Bt+ seed in 1994 and 1995, respectively (YieldGard, Monsanto, St.
      Louis, MO). At corn growth stage V6-V8, subplots within each mixture (15-20
      plants each) were infested so that every fifth plant in mixtures 1 and 4, every
      Bt- plant in mixture 2, and every Bt+ plant in mixture 3 received two egg masses.
      Larval sampling over a 21-d period indicated increased neonate dispersal off of
      Bt+ plants, reduced survival of larvae that dispersed from Bt+ plants to Bt-
      plants, and a low incidence of late-instar movement from Bt- plants to Bt+
      plants. Computer simulations based on mortality and dispersal estimates from this
      study indicate that seed mixtures will delay the evolution of resistant European
      corn borer populations compared with uniform planting of transgenic corn.
      However, resistant European corn borer populations likely will develop faster in
      seed mixes compared with separate plantings of Bt and non-Bt corn.

PMID- 10902354
TI  - Selection for fenpropathrin and fenpropathrin + acephate resistance in the
      silverleaf whitefly (Homoptera: Aleyrodidae).
AB  - A large, genetically diverse pool of Bemisia argentifolii Bellows & Perring was
      collected in 1994 from different crops, and a mixed colony was established in the
      laboratory. Subsets of this colony were reared on cotton plants held in large
      Plexiglas cages, and adult whiteflies were selected for resistance to
      fenpropathrin and to fenpropathrin + acephate (1:5). Selection was performed by
      exposing adults to treated glass vials at doses sufficient to give 60-80%
      mortality. Thirteen generations of adult selection with fenpropathrin + acephate
      yielded 856.3- and 1,289.3-fold tolerance (using lethal concentration ratio),
      respectively, to fenpropathrin and to fenpropathrin + acephate, indicating
      additive genetic variation for resistance in the source population. Selection
      with fenpropathrin alone yielded only a 10.9-fold increase in tolerance to
      fenpropathrin at the end of the selection period. There was no significant change
      in tolerance to fenpropathrin + acephate in this strain. Contrary to
      expectations, the early onset and the magnitude of resistance attained on
      selection with fenpropathrin + acephate compared with fenpropathrin alone
      indicates that this mixture evidently possesses a high degree of selectivity for
      development of resistance in B. argentifolii. Estimates of realized heritability
      of resistance to fenpropathrin and to fenpropathrin + acephate in B. argentifolii
      (in the fenpropathrin + acephate-selected strain) showed that they were
      significantly higher in the first half of selection (six generations), in both
      instances. Rearing of the fenpropathrin + acephate-resistant strain under
      conditions free of insecticides for six generations did not result in any
      significant decline in resistance, indicating that resistance is fairly stable.

PMID- 10902355
TI  - Correlated insecticide cross-resistance in azinphosmethyl resistant codling moth
      (Lepidoptera: Tortricidae).
AB  - Resistance to several classes of insecticides was correlated with azinphosmethyl
      resistance in codling moth, Cydia pomonella (L.), in California. In tests of
      laboratory and field populations, cross-resistance was positively correlated with
      azinphosmethyl and two organophosphates (diazinon, phosmet), a carbamate
      (carbaryl), a chlorinated hydrocarbon (DDT), and two pyrethroids (esfenvalerate
      and fenpropathrin). Additionally, negatively correlated cross-resistance was
      identified between azinphosmethyl and two other organophosphates, chlorpyrifos
      and methyl parathion. Patterns of resistance observed in laboratory colonies were
      confirmed with field bioassays. In bioassays of field populations, azinphosmethyl
      resistance was observed to increase from 1991 to 1993, although levels of
      resistance remained < 13-fold. Because orchards with azinphosmethyl resistance
      have had difficulties with suppression of codling moth, and cross-resistance was
      found for all tested classes of insecticides, strategies for managing resistance
      will need to be developed so as to protect current and future control tactics.
      The two insecticides with negatively correlated cross-resistance are discussed as
      potential tools for resistance management.

PMID- 10902356
TI  - Susceptibility of Plutella xylostella (L.) (Lepidoptera: Plutellidae) populations
      in Mexico to commercial formulations of Bacillus thuringiensis.
AB  - Populations of diamondback moth, Plutella xylostella (L.), sampled from
      commercial fields of crucifers in three states of Mexico, were tested for
      susceptibility to commercial formulations of Bacillus thuringiensis subsp.
      kurstaki (Berliner) (Dipel 2X), B. thuringiensis subsp. aizawai (XenTari), delta
      endotoxin Cry 1C (MC), and CryIA(c) (MVP), and a mixture of B. thuringiensis
      subsp. kurstaki and subsp. aizawai (Agree). Leaf-dip bioassays confirmed
      variation in susceptibility of up to 13-fold for MVP, 12-fold for Dipel 2X,
      sevenfold for XenTari, fivefold for Agree, and less than fivefold for MC.
      Comparisons with previously published data indicate that at least the 12-fold
      variation in Dipel 2X would result in significant differences in control in the
      field. Based on the LC99 values observed for the products, we propose
      discriminating concentrations for each product. To ensure continued performance
      in the field we suggest that a resistance monitoring program be implemented to
      detect any changes in susceptibility to B. thuringiensis products and specific
      toxins and that their use be restricted to one generation per crop and that they
      be rotated with other groups of insecticides. Furthermore, we suggest enforcement
      of a crucifer host-free period and the development and implementation of cultural
      and biological control strategies to reduce overall population pressure so that
      fewer insecticidal treatments will be needed.

PMID- 10902357
TI  - Life history study of multiple clones of insecticide resistant and susceptible
      greenbug Schizaphis graminum (Homoptera: Aphididae).
AB  - Comparative differences and similarities in prereproductive time (d), progeny
      production in a time equal to d (Md), and intrinsic rate of increase (rm) were
      established for one susceptible (S) and three resistant (R) strains of the
      greenbug, Schizaphis graminum (Rondani), reared on sorghum hybrids Dekalb G550E
      and Cargill 607E. The R strains showed three patterns of elevated esterase
      activity. Four R1 clones, four R2 clones, one R3 clone, and four S clones were
      evaluated. The interaction of sorghum hybrid and greenbug strain did not
      significantly influence any of the parameters measured. However, R1 greenbugs
      exhibited a significantly longer prereproductive period than the other strains.
      In addition, the R1 strain had a significantly slower intrinsic rate of increase
      than the R2 or S greenbug strains, but did not differ significantly from the R3
      strain. These results suggest that R1 greenbugs may be less fit than the other
      strains studied.

PMID- 10902358
TI  - Seasonal dynamics of cereal aphids on Russian wheat aphid (Homoptera: Aphididae)
      susceptible and resistant wheats.
AB  - Field experiments were conducted in 1997 and 1998 to evaluate the impact of
      resistance to Russian wheat aphid, Diuraphis noxia (Mordvilko), on the cereal
      aphid complex in wheat. Two spring wheats were planted: the variety "Centennial"
      (Russian wheat aphid susceptible) and the advanced line IDO488 (Russian wheat
      aphid resistant). IDO488 incorporates the resistance found in PI 294994 into a
      Centennial background. Field plots were artificially infested with adult D. noxia
      and sampled weekly. The most abundant aphid species in 1997 were Metopolophium
      dirhodum (Walker), Sitobion avenae (F.), D. noxia, and Rhopalosiphum padi (L.).
      In 1998, the order of abundance was M. dirhodum, R. padi, S. avenae, and D.
      noxia. The resistant genotype had significantly fewer D. noxia than the
      susceptible one during both years. However, plant genotype had no significant
      effect on the other aphid species in either year. Both the initial density of D.
      noxia and plant growth stage, had a significant effect on D. noxia population
      development, but had no effect on the other aphid species. There was no
      interaction between D. noxia resistance and the population density of the other
      aphid species observed.

PMID- 10902359
TI  - Conventional resistance of experimental maize lines to corn earworm (Lepidoptera:
      Noctuidae), fall armyworm (Lepidoptera: Noctuidae), southwestern corn borer
      (Lepidoptera: Crambidae), and sugarcane borer (Lepidoptera: Crambidae).
AB  - Plant resistance is a useful component of integrated pest management for several
      insects that are economically damaging to maize, Zea mays L. In this study, 15
      experimental lines of maize derived from a backcross breeding program were
      evaluated for resistance to corn earworm, Helicoverpa zea (Boddie); fall
      armyworm, Spodoptera frugiperda (J. E. Smith); southwestern corn borer, Diatraea
      grandiosella Dyar; and sugarcane borer, Diatraea saccharalis (F.). Experimental
      line 100-R-3 was resistant in the field to leaf feeding by fall armyworm and line
      116-B-10 was resistant in the field to leaf feeding by fall armyworm and leaf and
      stalk feeding by southwestern corn borer. When corn earworm larvae were fed field
      harvested silks from experimental line 81-9-B in the laboratory, their pupal
      weights were significantly lower than the pupal weights of larvae that were fed
      silks from the resistant control, Zapalote Chico. Maysin levels lower than those
      commonly associated with corn earworm resistance were present in the resistant
      experimental line, 107-8-7, indicating a new basis confers resistance to corn
      earworm in this line. These resistant experimental lines will provide plant
      breeders with new sources of resistance to lepidopterous insects for the
      development of improved maize breeding populations.

PMID- 10902360
TI  - Identification and quantification of hydroxamic acids in maize seedling root
      tissue and impact on western corn rootworm (Coleoptera: Chrysomelidae) larval
      development.
AB  - Hydroxamic acid content was analyzed in the root tissue of four maize, Zea mays
      L., lines using high-performance liquid chromatography (HPLC) and related to
      western corn rootworm, Diabrotica virgifera virgifera LeConte, larval development
      and survivorship. Maize lines evaluated included Mp710 (PI 596627), MpSWCB-4, (PI
      550498), Sc213 (PI 548792), and Dk580 (DeKalb commercial hybrid). Maize plants
      from each line were grown in test tubes containing a transparent agarose gel
      medium in a growth chamber. After 8 d of growth, root tissue of each line was
      harvested and hydroxamic acid content analyzed using HPLC. Three hydroxamic
      acids, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), 6
      methoxybenzoxazolinone (MBOA), and 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA),
      were identified in the maize roots tested. DIMBOA concentration was quantified
      and ranged from 246.37 +/- 70.53 micrograms to 91.84 +/- 49.82 micrograms DIMBOA
      per gram of root tissue. No significant difference was found among lines in D. v.
      virgifera larval development and survivorship.

PMID- 10902361
TI  - Performance of transgenic corn hybrids in Missouri for insect control and yield.
AB  - The efficacy of Bacillus thuringiensis-transformed corn (Zea mays L.) hybrids
      compared with comparable nontransformed corn hybrids for controlling first- and
      second-generation European corn borer, Ostrinia nubilalis (Hubner), and second
      generation southwestern corn borer, Diatraea grandiosella Dyar, was determined.
      Yield comparisons were obtained from the same plots of corn hybrids. Both
      generations of European and the second-generation of southwestern corn borer were
      effectively controlled, but the Bt hybrids varied in degree of control. Hybrids
      from Ciba Seeds, DEKALB, and Mycogen had more European corn borer tunneling than
      those from Novartis or Cargill, and this was generally ascribed to different
      transgenic events. The Bt-transformed hybrids had virtually no leaf-feeding
      damage and less tunneling than the non-Bt corn hybrids. Some Bt corn hybrids had
      no tunneling, whereas other Bt hybrids had a small amount of tunneling. All of
      the non-Bt hybrids had significant leaf-feeding damage and stalk tunneling from
      both insects. Only three live European corn borer larvae (stunted) were found in
      the Bt corn hybrids while splitting stalks to assess tunnel length. When insect
      damage was significant, and in some evaluations where damage was not significant,
      differences in yields among hybrids were observed. No significant insect
      population differences were observed for five genera of beneficial insects for Bt
      versus non-Bt corn hybrids. Corn hybrids that have been transformed with the Bt
      gene provide an effective means of control for corn borers and efforts to reduce
      the likelihood of development of borer resistance are warranted.

PMID- 10902362
TI  - Plant resistance components of two greenbug (Homoptera: Aphididae) resistant
      wheats.
AB  - Several biotypes of the greenbug, Schizaphis graminum (Rondani), attack winter
      wheat, Triticum aestivum L., on the Southern Plains every year. Two wheat
      germplasm sources of resistance ('Largo' and 'GRS 1201') have been developed that
      provide protection against the three predominant greenbug biotypes (E, I, and K).
      Each source has agronomic and end-use quality advantages and disadvantages for
      the breeder to consider in choosing a greenbug-resistant breeding line. We
      compared these two germplasms to determine their levels of resistance against
      biotype E. Components of resistance (i.e., antibiosis, antixenosis, and
      tolerance) were measured on seedlings of GRS 1201, Largo, and 'TAM W-101' (a
      susceptible control). Several aphid and plant measurements (e.g., total number of
      aphids produced per plant, aphid selection preferences, and plant damage ratings)
      were recorded for each plant entry. Select data recorded for each resistance
      component were normalized and combined to derive a plant resistance index for
      each wheat entry. Results indicated that GRS 1201 had a higher level of combined
      resistance components than did Largo, followed by TAM W-101, the susceptible
      control. These data provide additional information for the breeder to consider in
      selecting a greenbug-resistant breeding line.

PMID- 10902363
TI  - Evaluation of trap types and food attractants for Rhagoletis cerasi (Diptera:
      Tephritidae).
AB  - Trapping experiments were conducted during the period of flight activity of the
      cherry fruit fly Rhagoletis cerasi L. in the area of Thessaloniki, northern
      Greece, during the years 1993-1997 to test several traps alone and in combination
      with different food attractants. Yellow sticky-coated visual traps were more
      effective than McPhail-type traps baited with different food attractants. Of the
      visual traps, the most effective was the yellow Rebell trap. The Rebell trap,
      provided with a dispenser containing a slow release formulation of ammonium
      acetate attached to the lower part of the trap, was found to be the most
      effective of all treatments tested, capturing approximately 50% more R. cerasi
      flies than the Rebell trap without any attractant. Ammonium carbonate dispensers
      did not increase the performance of Rebell traps. More mature females were
      captured in Rebell traps baited with or without ammonium acetate than in McPhail
      type traps baited with ammonium acetate. This study demonstrates that Rebell
      traps baited with an ammonium acetate dispenser can provide a more effective tool
      for monitoring and mass trapping of R. cerasi than the currently used unbaited
      Rebell traps.

PMID- 10902364
TI  - Effects of transgenic Bacillus thuringiensis maize grain on B. thuringiensis
      susceptible Plodia interpunctella (Lepidoptera: Pyralidae).
AB  - Percentage survivorship, developmental time, adult body length, and sex ratio of
      Plodia interpunctella (Hubner) reared on field-produced grain from sixteen
      cultivars of maize, Zea mays L., including several transgenic Bacillus
      thuringiensis (Bt) Berliner hybrids and selected non-Bt isolines, were evaluated
      under laboratory conditions. Compared with isolines, development was delayed and
      survivorship reduced for P. interpunctella reared on grain from transgenic
      hybrids with the CaMV/35s promoter that express Cry1Ab protein. Similarly,
      compared with non-Bt hybrids, a transgenic hybrid with the CaMV/35s promoter that
      expresses Cry9C protein delayed development, decreased survivorship, and caused
      reductions in adult body length of P. interpunctella. In contrast, no significant
      differences in P. interpunctella developmental times or survivorship were
      observed between transgenic hybrids with the PEPC promoter expressing Cry1Ab and
      their isolines. Additionally, developmental time, survivorship, and adult body
      length were similar between P. interpunctella reared on a transgenic hybrid with
      the CaMV/35s promoter expressing Cry1Ac and non-Bt hybrids. Our data demonstrate
      that transgenic Bt maize grain, especially grain from hybrids with the CaMV/35s
      promoter expressing Cry1Ab or Cry9C, can significantly affect B. thuringiensis
      susceptible P. interpunctella populations up to 4 or 5 mo after harvest.

PMID- 10902365
TI  - Hot water treatment and insecticidal coatings for disinfesting limes of mealybugs
      (Homoptera: Pseudococcidae).
AB  - Hot water immersion and insecticidal coatings were tested to determine if they
      could be used to disinfest Persian limes, Citrus latifolia Tanaka, of the
      mealybug pests Planococcus citri Risso and Pseudococcus odermatti Miller &
      Williams. A 20-min 49 degrees C hot water immersion treatment is effective in
      killing mealybugs and all other arthropods tested found externally on limes, or
      under the calyx. No insects or mites were found to survive after the 20-min hot
      water treatment. In this test, 7,200 limes were treated with 1,308 insects killed
      and zero survivors. Treatment at 49 degrees C for 20 min did not significantly
      affect quality when treated fruit were compared with untreated control fruit.
      Four coatings were tested at a 3% rate: two petroleum-based oils (Ampol and
      Sunspray oil), a vegetable oil (natural oil), and a soap (Mpede). The coatings
      gave up to 94% kill (Ampol) of mealybugs, which is not sufficient to provide
      quarantine security. The coatings might be effective as a postharvest dip before
      shipment.

PMID- 10902366
TI  - Laboratory rearing of lesser appleworm (Lepidoptera: Tortricidae).
AB  - The lesser appleworm, Cydia prunivora (Walsh), was reared successfully in the
      laboratory. Larvae of various instars were collected in the field from hawthorn
      fruit, Crataegus spp. Initially, immature apples served as the food source for
      the larvae in the laboratory. Rearing was conducted in a greenhouse and later in
      combination with a controlled environment room at 25 degrees C, 50-60% RH, and a
      photoperiod of 18:6 (L:D) h. Under these conditions, a generation required
      approximately 30 d. Fifty-six adult lesser appleworm moths emerged from the
      original field collected hawthorn fruits. After a decline in the number of the F1
      generation to 39 moths, the colony on mature apples, increased to in excess of
      10,000 moths by the fifth generation with a mean survival rate to adult of 68.0%.
      When production on immature apples was compared with that on four artificial
      diets, the most promising of the artificial diets was the lima bean-based diet
      currently used to rear the oriental fruit moth, Cydia molesta (Busck), with a
      mean survival rate of 46.4%. The other bean-based diets tested were not as
      satisfactory. Pear foliage was the preferred oviposition substrate of those
      tested, including apple and hawthorn foliage. No eggs were deposited on plain
      waxed paper or glass microscope slides; however, large numbers of eggs were
      deposited on waxed paper treated with a water extract of pear foliage and
      immature apples.

PMID- 10902367
TI  - Large-scale, on-site confirmatory, and varietal testing of a methyl bromide
      quarantine treatment to control codling moth (Lepidoptera: Tortricidae) in
      nectarines exported to Japan.
AB  - In total, 30,491 codling moth, Cydia pomonella (L.), 1-d-old eggs on May Grand
      nectarines in two large-scale tests, and 17,410 eggs on Royal Giant nectarines in
      four on-site confirmatory tests were controlled with 100% mortality after
      fumigation with a methyl bromide quarantine treatment (48 g3 for 2 h at > or = 21
      degrees C and 50% volume chamber load) on fruit in shipping containers for export
      to Japan. Ranges (mean +/- SEM) were for percentage sorption 34.7 +/- 6.2 to 46.5
      +/- 2.5, and for concentration multiplied by time products 54.3 +/- 0.9 to 74.5
      +/- 0.6 g.h/m3 in all tests. In large-scale tests with May Grand nectarines,
      inorganic bromide residues 48 h after fumigation ranged from 6.8 +/- 0.7 to 6.9
      +/- 0.5 ppm, which were below the U.S. Environmental Protection Agency tolerance
      of 20 ppm; and, organic bromide residues were < 0.01 ppm after 1 d and < 0.001
      ppm after 3 d in storage at 0-1 degree C. After completion of larger-scale and on
      site confirmatory test requirements, fumigation of 10 nectarine cultivars in
      shipping containers for export to Japan was approved in 1995. Comparison of LD50s
      developed for methyl bromide on 1-d-old codling moth eggs on May Grand and Summer
      Grand nectarines in 1997 versus those developed for nine cultivars in the
      previous 11 yr showed no significant differences in codling moth response among
      the cultivars.

PMID- 10902368
TI  - Response of omnivorous leafroller (Lepidoptera: Tortricidae) and onion thrips
      (Thysanoptera: Thripidae) to low-temperature storage.
AB  - Eggs and first-fifth instars of omnivorous leafroller, Platynota stultana
      Walshingham, had a mean percentage survival to the adult stage of 60.7-95.2% for
      nonexposed immatures and 14.5-54.3% for immatures exposed to 1 wk at 0-1 degree
      C. Exposures of 2-5 wk resulted in 0-6.7% survival, and a 6-wk exposure resulted
      in < 1% survival of all stages tested. A significant reduction in survival of all
      larval stages occurred between exposures of 0 and 1 wk and between 1 wk and 2-6
      wk. Survival of eggs after exposures of 0 and 1 wk was significantly different
      than survival after exposures of 2-6 wk. The second instar was the stage least
      susceptible to low-temperature storage. Adults that were exposed to low
      temperature for 1 wk in the third through fifth instars laid a mean of 120-289
      eggs per female, and the mean percentage viability of the eggs ranged from 56.2
      to 71.4%. Mean percentage survival of adults and nymphs of onion thrips, Thrips
      tabaci Lindeman, was inversely related to the duration of exposure from 1 through
      3-6 wk at 0-1 and 5 degrees C and was lower at 0-1 (0.2-52.5%) than at 5 degrees
      C (17.6-66.6%). Exposure to 0-1 degree C for 4 wk attained 91.2% control, which
      increased to 99.8% after 6 wk. Low-temperature storage has potential to control
      omnivorous leafroller in table grapes, Vitis vinifera L., and onion thrips in
      onions, Allium cepa L.

PMID- 10902369
TI  - Insect infestation of stored oats in Florida and field evaluation of a device for
      counting insects electronically.
AB  - Automated methods of monitoring stored grain for insect pests will contribute to
      early detection and aid in management of pest problems. An insect population
      infesting stored oats at a seed processing plant in north-central Florida was
      studied to test a device for counting insects electronically (Electronic Grain
      Probe Insect Counter, EGPIC), and to characterize the storage environment. The
      device counts insects as they fall through an infrared beam incorporated into a
      modified grain probe (pitfall) trap and transmits the counts to a computer for
      accumulation and storage. Eight traps were inserted into the surface of the grain
      bulk, and the insects trapped were identified and counted manually at weekly
      intervals. Grain temperature and moisture content also were recorded for each
      trap location. Manual and automatic counts were compared to estimate error in the
      EGPIC system. Both over- and undercounting occurred, and errors ranged from -79.4
      to 82.4%. The mean absolute value of error (+/- SE) was 31.7% (+/- 4.3). At least
      31 species, or higher taxa, were detected, but the psocid Liposcelis entomophila
      (Enderlein) and the foreign grain beetle, Ahasverus advena (Waltl), accounted for
      88% of the captured insects. Species diversity, phenology, and spatial
      distribution are presented, as well as temporal and spatial distribution of grain
      temperature and moisture content. The data sets generated will find application
      in population modeling and development of integrated pest management systems for
      stored grain.

PMID- 10902370
TI  - Monitoring northern fowl mites (Acari: Macronyssidae) in caged laying hens:
      feasibility of an egg-based sampling system.
AB  - Northern fowl mites were monitored on a caged-layer operation in southern
      California for 22 mo. Three experienced observers underestimated actual numbers
      of mites in the vent region approximately 80% of the time. Errors were higher for
      heavy infestations. Observer estimates were highly correlated with each other (r
      > 0.89, P < 0.01) and with mite numbers estimated by vent feather removal (r >
      0.82, P < 0.01). Mites on hens varied between houses and over time. Molting
      consistently reduced mite numbers, but did not eliminate then in a flock. Long
      term monitoring of individual sentinel hens demonstrated that some hens would
      support high numbers of mites for several months or more. Use of a new sequential
      hen sampling plan required approximately 1 min per hen, if mite numbers were
      estimated. At this site, treatment decisions often could be reached in < 20 min
      per house. Mite scores (index of estimated mites per hen) were well correlated
      with percentage of hens infested in both test houses. In a chronically infested
      house, prevalence of mites on eggs averaged 8.5%, with a range of 0-55%.
      Applications of tetrachlorvinphos-dichlorvos by the producer appeared to be based
      on mites on > about 20% of eggs. The chemical was marginal for controlling mites
      on hens (25% reduction in percentage of hens infested), but effectively reduced
      mites on eggs (95% fewer mites on eggs at 1 wk and 90% at 2 wk). When data were
      grouped by mite index score on hens, there was a strong relationship (r2 = 0.83,
      P < 0.01) between mite prevalence on eggs and the scores of the hens which laid
      them. Sampling 100 eggs evenly spaced in a house required < 7 min, and adult
      mites were easily seen. Sampling mites on eggs appears to be useful to localize
      at least high-level infestations, and egg-based sampling for mites merits further
      investigation.

PMID- 10902371
TI  - Conceptualizing and measuring global interpersonal mistrust-trust.
AB  - Global interpersonal mistrust is conceptualized as a general mistrust of the
      motives of others in situations related to one's well-being: a general tendency
      to view others as mean, selfish, malevolent, or unreliable people who are, thus,
      not to be depended on to treat one well. The authors developed an 18-item
      unidimensional self-report inventory measuring interpersonal mistrust as a
      negative cognitive orientation toward others. The measure comprises items
      describing perceptions of specific hypothetical interpersonal situations rather
      than items asking respondents to describe their own general behavior. The measure
      was reliable and evidenced construct validity in a heterogeneous sample of
      Australians.

PMID- 10902372
TI  - Supervisor support in the work place: legitimacy and positive affectivity.
AB  - The authors tested 3 hypotheses regarding supervisor support in the work place.
      The validation hypothesis predicts that when employees are supported by their
      coworkers and the larger organization, they also receive more support from their
      supervisors. The positive affectivity hypothesis predicts that employees with
      positive dispositions receive more supervisor support because they are more
      socially oriented and likable. The moderation hypothesis predicts a joint
      multiplicative effect between validation and positive affectivity. An assessment
      of the hypotheses among a sample of 1,882 hospital employees in Korea provided
      strong support for the validation and moderation hypotheses.

PMID- 10902373
TI  - The dimensionality of coping among Chinese health care workers.
AB  - The transactional model defines coping as a process that changes on the basis of
      the context of an environmental encounter. An instrument used to investigate
      coping in diverse person-environment interactions is the Ways of Coping
      Questionnaire (WOC; S. Folkman & R. S. Lazarus, 1988). Although evidence exists
      to support the basic underlying structure of the WOC in Western societies, no
      research has been conducted on the instrument's dimensionality in non-Western
      societies. The authors identified 14 factors for the WOC administered to a sample
      of health care workers in Beijing, China. The 14 factors identified in the
      present study were similar to the 8 factors identified in the original validation
      study (S. Folkman, R. S. Lazarus, C. Dunkel-Schetter, A. DeLongis, & R. J. Gruen,
      1986), but they were more content specific.

PMID- 10902374
TI  - Psychological predictors of coping responses among Greek basketball referees.
AB  - The authors examined the effects of situational appraisals (perceived control and
      intensity), coping styles (monitoring and blunting), and personal dispositions
      (optimism and self-esteem) on the approach and avoidance coping responses of
      skilled Greek basketball referees (N = 162) and the consistency of their
      responses following 3 game-related stressful situations. In an effort to clarify
      the variables involved in coping and to consider the theoretical principles both
      within and beyond sports, the authors replicated an earlier study among
      Australian basketball referees (A. Kaissidis-Rodafinos, M. H. Anshel, & A.
      Porter, 1997). The results were equivocal: The Greek referees were not consistent
      in using avoidance and approach coping responses across situations. Approach
      coping was more predictable than avoidance coping in accounting for both
      situational and personal variables.

PMID- 10902375
TI  - Learning achievement, social adjustment, and family conflict among Bedouin-Arab
      children from polygamous and monogamous families.
AB  - A sample of 146 Bedouin-Arab pupils from polygamous and monogamous families
      participated in this study, which was conducted in a Bedouin-Arab village in the
      Negev, Israel. The authors compared learning achievement, social adjustment, and
      family conflict. Data revealed differences between the two groups: The children
      from monogamous families had higher levels of learning achievement than did the
      children from polygamous families; in addition, those from monogamous families
      adjusted to the school framework better than did those from polygamous families.
      The mean conflict rating of children from polygamous families was higher than
      that of their counterparts from monogamous families. The father's level of
      education tended to be inversely correlated with family size in terms of both
      number of children and number of wives.

PMID- 10902376
TI  - Parenting among Hispanic and Anglo-American mothers with young children.
AB  - The authors examined parenting practices and developmental expectations among 38
      Hispanic and 38 Anglo-American mothers living in the United States. Mothers of
      children 3 to 5 years of age completed the Parent Behavior Checklist (R. A. Fox,
      1994), a 100-item measure of parents' developmental expectations, discipline, and
      nurturing practices. In addition, the authors appraised the Hispanic mothers'
      acculturation and selected them for participation if their scores on an
      acculturation scale indicated (a) that their lifestyle was predominantly Hispanic
      and (b) that they had not been assimilated into the dominant culture. The 2
      ethnic groups were also divided by socioeconomic status (SES). There were
      significant main effects for ethnicity and SES on the discipline and nurturing
      scores but not on the expectations scores. The Hispanic and higher SES mothers
      reported higher discipline and lower nurturing scores than did the Anglo-American
      and lower SES mothers. An unexpected finding was the tendency for higher SES
      Hispanic mothers to report more frequent use of discipline than the other 3
      groups.

PMID- 10902377
TI  - Impact of marketing work-place diversity on employee job involvement and
      organizational commitment.
AB  - Much of the debate about managing work-force diversity concerns the rationale for
      the procedures used and the outcomes produced by programs perceived to be unfair.
      The authors explored the role of organizational justice in diversity initiatives;
      they examined which of 6 diversity arguments (T. H. Cox & S. Blake, 1991) were
      most often used by U.S. firms and accepted by employees. They also surveyed U.S.
      workers about diversity issues at work; the problem-solving diversity argument
      was related to higher employee job involvement and organizational commitment,
      even though the respondents ranked the resource-acquisition argument as the most
      acceptable. The authors also found that many organizational-justice issues still
      need to be resolved, even in those organizations with diversity-management
      programs.

PMID- 10902378
TI  - Altruistic organizational citizenship behavior: context, disposition, and age.
AB  - The authors proposed employee age as moderating the structural stability of
      altruistic organizational citizenship behavior (OCB) with regard to the influence
      of context-relevant attitudes and dispositional variables. Analyses of peer
      ratings of altruistic OCB in a sample of 96 U.S. nurses showed that the
      contextual variables of job satisfaction, organizational commitment, and trust in
      management were germane for the younger participants. The dispositional variable
      of moral judgment was a unique predictor of altruistic OCB among the older
      participants.

PMID- 10902379
TI  - Controllability, anger, judgments, and valence in attributions for civil unrest.

PMID- 10902380
TI  - An analysis of the impact of the work environment on chartered accountants'
      professional examination performance.

PMID- 10902381
TI  - The influence of gasoline formulation on specific pollutant emissions.

PMID- 10902382
TI  - Learnings to practitioners of the science being discussed.

PMID- 10902383
TI  - Lifetime emissions.

PMID- 10902384
TI  - Characterization of activated carbon fiber filters for pressure drop,
      submicrometer particulate collection, and mercury capture.
AB  - The use of activated carbon fiber (ACF) filters for the capture of particulate
      matter and elemental Hg is demonstrated. The pressure drop and particle
      collection efficiency characteristics of the ACF filters were established at two
      different face velocities and for two different aerosols: spherical NaCl and
      combustion-generated silica particles. The clean ACF filter specific resistance
      was 153 kg m-2 sec-1. The experimental specific resistance for cake filtration
      was 1.6 x 10(6) sec-1 and 2.4 x 10(5) sec-1 for 0.5- and 1.5-micron mass median
      diameter particles, respectively. The resistance factor R was approximately 2,
      similar to that for the high-efficiency particulate air filters. There was a
      discrepancy in the measured particle collection efficiencies and those predicted
      by theory. The use of the ACF filter for elemental Hg capture was illustrated,
      and the breakthrough characteristic was established. The capacity of the ACF
      filter for Hg capture was similar to other powdered activated carbons.

PMID- 10902385
TI  - Particle mass emission rates from current-technology, light-duty gasoline
      vehicles.
AB  - Now that the U.S. Environmental Protection Agency has promulgated new National
      Ambient Air Quality Standards for PM2.5, work will begin on generating the data
      required to determine the sources of ambient PM2.5 and the magnitude of their
      contributions to air pollution. This paper summarizes the results of an
      Environmental Research Consortium program, carried out under the auspices of the
      U.S. Council for Automotive Research. The program focused on particulate matter
      (PM) emissions from representative, current-technology, light-duty gasoline
      vehicles produced by DaimlerChrysler Corp., Ford Motor Co., and General Motors
      Corp. The vehicles, for the most part taken from the manufacturer's certification
      and durability fleets, were dynamometer-tested using the three-phase Federal Test
      Procedure in the companies' laboratories. The test fleet was made up of a mixture
      of both low-mileage (2K-35K miles) and high-mileage (60K-150K miles) cars, vans,
      sport utility vehicles, and light trucks. For each vehicle tested, PM emissions
      were accumulated over 4 cold-start tests, which were run on successive days. PM
      emission rates from the entire fleet (22 vehicles total) averaged less than 2
      mg/mile. All 18 vehicles tested using California Phase 2 reformulated gasoline
      had PM emission rates less than 2 mg/mile at both low and high mileages.

PMID- 10902386
TI  - The effect of coal combustion flue gas components on low-level chlorine
      speciation using EPA method 26A.
AB  - U.S. Environmental Protection Agency (EPA) Method 26A is the recommended
      procedure for capturing and speciating halogen (X2) and hydrogen halide (HX)
      stack emissions from combustion sources. Previous evaluation studies of Method
      26A have focused primarily on hydrogen chloride (HCl) speciation. Capture
      efficiency, bias, and the potential interference of Cl2 at high levels (> 20 ppm
      [microgram/m3]) and NH4Cl in the flue gas stream have been investigated. It has
      been suggested that precise Cl2 measurement and accuracy in quantifying HX or X2
      using Method 26A are difficult to achieve at Cl2 concentrations < 5 ppm; however,
      no performance data exist to support this. Coal contains low levels of Cl, in the
      range of 5-2000 ppmw, which results in the presence of HCl and Cl2 in the
      products of combustion. HCl is the predominant Cl compound formed in the high
      temperature combustion process, and it persists in the gas as the products of
      combustion cool. Concentrations of Cl2 in coal combustion flue gas at stack
      temperatures typically do not exceed 5 ppm. For this research, bench-scale
      experiments using simulated combustion flue gas were designed to validate the
      ability of Method 26A to speciate low levels of Cl2 accurately. This paper
      presents the results of the bench-scale tests. The effect of various flue gas
      components is discussed. The results indicate that SO2 is the only component in
      coal combustion flue gas that has an appreciable effect on Cl2 distribution in
      Method 26A impingers, and that Method 26A cannot accurately speciate HCl and Cl2
      in coal combustion flue gas without modification.

PMID- 10902387
TI  - What is the potential measurement error in occupational exposure studies?
AB  - This paper demonstrates statistical methods that estimate measurement error from
      available industrial hygiene data. Errors in measuring a continuous exposure
      variable may arise when all individuals in a work area are assigned the same
      exposure. An example is when the mean of exposure measurements obtained on a
      sample of individuals is assigned to all workers with similar jobs. This may lead
      to inaccurate point and interval estimates in exposure-response modeling. A
      method of simulating the distribution of true (i.e., unobserved) individual
      exposures is described in order to estimate the mean and variance of measurement
      error. The minimum variance unbiased estimator approximates the mean of
      lognormally distributed exposure measurements. The distribution of true
      individual exposures is approximated by the distribution of simulated estimates
      of mean exposure. The methodology is illustrated by exposure data from work areas
      manufacturing refractory ceramic fiber (RCF) and RCF products. Results show that
      exposure is slightly underestimated in work areas with between 25 and 113
      exposure measurements; measurement error variance averages about 1.3% of the
      total variance.

PMID- 10902388
TI  - Reduction in residential chromium following site remediation.
AB  - The purpose of this study was to determine the influence of chromate production
      waste site remediation on residential Cr concentrations in house dust. Twenty
      three homes in Jersey City, NJ, were identified as having had high (> 500
      micrograms/gm, median 739 micrograms/gm), medium (100-400 micrograms/gm, median
      245 micrograms/gm), or low (< 100 micrograms/gm, median 48 micrograms/gm) Cr in
      house dust during a study conducted in 1992-1993 prior to site remediation. House
      dust samples were collected on four visits from each home between November 1996
      and February 1998, extracted with HNO3, and analyzed for Cr with an inductively
      coupled plasma-mass spectrometer. Homes that had low Cr concentrations in 1992
      1993 continued to have low Cr concentrations (median 1 microgram/g). In contrast,
      substantial declines in Cr concentrations were found in the house dust collected
      from homes located near the remediated waste sites: previously high-level homes
      had a median of 50 micrograms/g and mid-level homes had a median of 34
      micrograms/g. Site remediation had a beneficial effect on household loadings of
      Cr, since no differences in post-remediation house dust Cr concentrations were
      found among the three groups.

PMID- 10902389
TI  - A sorptive slurry bioscrubber for the control of acetone.
AB  - A sorptive slurry bioscrubber adds powdered activated carbon (PAC) to a
      conventional suspended-growth bioscrubber. The activated carbon increases
      pollutant removal from the gas phase due to adsorption on carbon. The carbon is
      bioregenerated in the oxidation reactor and recycled to the scrubbing column. A
      three-stage, conventional bioscrubber was tested with and without carbon. The
      experiments showed that the PAC improved the removal efficiency of the system and
      that bioregeneration occurred. At an inlet gas-phase acetone concentration of 50
      ppmv, the steady-state removal increased from 88 to 95% when activated carbon was
      added to the biological slurry.

PMID- 10902390
TI  - Ozone formation in California's San Joaquin Valley: a critical assessment of
      modeling and data needs.
AB  - Data from the 1990 San Joaquin Valley Air Quality Study/Atmospheric Utility
      Signatures, Predictions, and Experiments (SJVAQS/AUSPEX) field program in
      California's San Joaquin Valley (SJV) suggest that both urban and rural areas
      would have difficulty meeting an 8-hr average O3 standard of 80 ppb. A conceptual
      model of O3 formation and accumulation in the SJV is formulated based on the
      chemical, meteorological, and tracer data from SJVAQS/AUSPEX. Two major phenomena
      appear to lead to high O3 concentrations in the SJV: (1) transport of O3 and
      precursors from upwind areas (primarily the San Francisco Bay Area, but also the
      Sacramento Valley) into the SJV, affecting the northern part of the valley, and
      (2) emissions of precursors, mixing, transport (including long-range transport),
      and atmospheric reactions within the SJV responsible for regional and urban-scale
      (e.g., down-wind of Fresno and Bakersfield) distributions of O3. Using this
      conceptual model, we then conduct a critical evaluation of the meteorological
      model and air quality model. Areas of model improvements and data needed to
      understand and properly simulate O3 formation in the SJV are highlighted.

PMID- 10902391
TI  - Improved spatial allocation methodology for on-road mobile emissions.
AB  - Emissions from automobiles and trucks operating on public roads represent a major
      portion of the air pollutants included in emission inventories. When emission
      data are prepared for air quality modeling studies, such as those supporting
      development of a State Implementation Plan, an emission processor matches the
      spatial and temporal resolution of the emissions to the requirements of the
      modeling study. However, the spatial location of vehicular emissions is not known
      and must be estimated. This paper presents a methodology for determining the
      spatial distribution of the roads belonging to a road class using geospatial data
      functions, such as those commonly provided by a geographic information system.
      Vehicle-miles traveled (VMT) are then allocated to medium-resolution (12 x 12-km)
      and fine-resolution (4 x 4-km) modeling grids using both this methodology and the
      existing top-down methodology, which uses population density. The results show a
      significant difference in the spatial distribution of VMT between these two
      methodologies. Based upon these results, we recommend using the road class
      specific methodology in lieu of the population methodology for spatially
      allocating vehicular emissions for medium- and finer-resolution modeling grids.

PMID- 10902392
TI  - A fabric denuder for sampling semi-volatile species.
AB  - A new style of diffusion denuder has been evaluated specifically for sampling
      HNO3. A coated fabric is used as the denuder substrate, which can be loaded
      directly into a standard filter holder. This approach allows direct denuder
      sampling with no additional capital costs over filter sampling and simplifies the
      coating and extraction process. Potential denuder materials and coatings were
      evaluated in the laboratory to test the removal efficiency. NaCl coatings were
      used to assess more than 20 materials for HNO3 collection efficiency. Particle
      retention, which would cause a denuder to have a positive bias for gas
      concentration measurements, was evaluated by ambient air sampling using
      particulate sulfate as the reference aerosol. Particle retention varied from 0 to
      15%, depending on the denuder material tested. The best performing material
      showed an average particle retention of less than 3%. Denuder efficiency of four
      fabric materials was tested under ambient conditions to determine removal
      efficiency. The fabric denuder method was compared with a long path-length
      Fourier transform infrared (FTIR) spectrometer, a tunable diode laser absorption
      spectrometer (TDLAS), and a denuder difference sampler to independently measure
      HNO3. HNO3 collection efficiency was typically 90% for the denuders, whether
      coated with NaCl or not. For 10-L/min sampling rates with the fabric denuder, the
      square of the correlation coefficient with the FTIR spectrometer was 0.73,
      compared to 0.24 with the TDLAS.

PMID- 10902393
TI  - A life-cycle inventory model of municipal solid waste combustion.
AB  - Evaluation of alternate strategies for municipal solid waste (MSW) management
      requires models to calculate environmental emissions as a function of both waste
      quantity and composition. A methodology to calculate waste component-specific
      emissions associated with MSW combustion is presented here. The methodology
      considers emissions at a combustion facility as well as those avoided at an
      electrical energy facility because of energy recovered from waste combustion.
      Emission factors, in units of kg pollutant per metric ton MSW entering the
      combustion facility, are calculated for CO2-biomass, CO2-fossil, SOx, HCl, NOx,
      dioxins/furans, PM, CO, and 11 metals. Water emissions associated with electrical
      energy offsets are also considered. Reductions in environmental emissions for a
      500-metric-ton-per-day combustion facility that recovers energy are calculated.

PMID- 10902394
TI  - Assessment of the application of an ecotoxicological procedure to screen illicit
      toxic discharges in domestic septic tank sludge.
AB  - An innovative screening procedure has been developed to detect illicit toxic
      discharges in domestic septic tank sludge hauled to the Montreal Urban Community
      waste-water treatment plant. This new means of control is based on an integrative
      approach, using bioassays and chemical analyses. Conservative criteria are
      applied to detect abnormal toxicity with great reliability while avoiding false
      positive results. The complementary data obtained from toxicity tests and
      chemical analyses support the use of this efficient and easy-to-apply procedure.
      This study assesses the control procedure in which 231 samples were analyzed over
      a 30-month period. Data clearly demonstrate the deterrent power of an efficient
      control procedure combined with a public awareness campaign among the carriers.
      In the first 15 months of application, between January 1996 and March 1997,
      approximately 30% of the 123 samples analyzed showed abnormal toxicity. Between
      April 1997 and June 1998, that is, after a public hearing presentation of this
      procedure, this proportion dropped significantly to approximately 9% based on 108
      analyzed samples. The results of a 30-month application of this new control
      procedure show the superior efficiency of the ecotoxicological approach compared
      with the previously used chemical control procedure. To be able to apply it
      effectively and, if necessary, to apply the appropriate coercive measures,
      ecotoxicological criteria should be included in regulatory guidelines.

PMID- 10902395
TI  - Performance testing of a multimetals continuous emissions monitor.
AB  - A prototype instrument, designed for continuous monitoring of hazardous air
      pollutant metal emissions in the stack gases of waste incinerators and industrial
      furnaces, has undergone a performance evaluation that included a relative
      accuracy test audit. The test results confirmed the instrument's ability to
      accurately measure stack gas metal concentrations and thus validate the
      applicability of the candidate technique for compliance assurance monitoring for
      the specific source involved. The analytical accuracy of this system, documented
      during the recent test exercise, represents a significant improvement in
      performance relative to that previously achieved, and can be attributed with
      certainty to the recent implementation of a shrouded nozzle sampling system. By
      reducing deposition losses of particulate matter in the extracted stack gas
      stream to acceptable levels, presentation of a more representative sample stream
      to the elemental analyzer has been accomplished. The present paper discusses the
      design and operation of the multimetals continuous emissions monitor (MMCEM), the
      shrouded nozzle sampling system, and the results of recent performance testing.

PMID- 10902396
TI  - Patterns and concentrations of PM10 in a mountainous basin region.
AB  - In this study, continuous data of PM10 (particles with aerodynamic diameter < 10
      microns) concentration measurements for a 4-yr period were analyzed. These
      measurements have been carried out in the Eordea Basin, an industrial area in the
      northwestern mountainous region of Greece. The annual, monthly, and diurnal
      patterns are presented and investigated regarding the prevailing meteorological
      conditions and atmospheric processes that affect the ambient concentrations of
      PM10. The effect of wind on controlling PM10 concentration is also discussed.
      Based on the data analysis, an attempt is made to provide useful information
      about air quality levels, taking into account U.S. Environmental Protection
      Agency air quality standards.

PMID- 10902397
TI  - An alternative approach to photochemical ozone creation potentials applied under
      European conditions.
AB  - Photochemical ozone creation potential (POCP) values for 83 different volatile
      organic compounds (VOCs), including CO and CH4, were calculated under different
      environmental conditions representative for Europe. These calculations show that
      variations in POCP values are large between different types of chemical
      environments and that POCP values for VOCs should be presented as ranges instead
      of single values. POCP ranges are based on the extremes of the POCP values and
      are defined with the intention to include all POCP values an individual VOC will
      obtain in any European environment where O3 formation is of environmental
      concern. The POCP ranges indicate large differences in O3 production between
      individual VOCs, which justifies the use of this ranking scale instead of
      treating all VOCs as a homogeneous group of species in abatement strategies. Both
      the average O3 production over 96 hr and the maximum contribution to the O3
      concentration were studied. The most efficient O3 producers were found to be
      isoprene, 2-methyl-2-butene, and acrolein. As a group, the alkenes are the most
      potent O3 producers, followed by higher alkanes and then the aromatics. The
      calculated values show a good agreement with previously calculated POCP values
      under northern European conditions.

PMID- 10902398
TI  - Optimal loading rates and economic analyses for anaerobic digestion of poultry
      waste.
AB  - Four combinations of litter and carcasses from broiler chickens were examined
      utilizing a thermophilic, stirred-tank digester of demonstration size of
      approximately 10,000 gal. Under computed optimal loading rates, litter with paper
      bedding had the highest daily production of methane over an 8-day retention
      period. The greatest methane production per lb of volatile solids was achieved
      over 10 days with litter and paper bedding combined with carcasses. This research
      found that sufficient poultry litter is generated within 20 mi (32 km) of
      Moorefield, WV, to support a commercial-sized digester operation. However,
      anaerobic digestion of poultry waste cannot be financially supported by methane
      production alone. To be financially viable, anaerobic digestion requires a
      disposal fee for poultry waste and/or the sale of the digested solid effluent as
      an organic fertilizer to retail markets.

PMID- 10902399
TI  - Long-term monitoring and analysis of hourly solar UV radiation in the 290-380 nm
      range in the middle region of Saudi Arabia.
AB  - The UV and global solar radiation on a horizontal surface at ground level in
      Riyadh City (latitude 24 degrees 34' N, longitude 46 degrees 43' E) have been
      measured and analyzed. Measurements of UV radiation (295-385 nm) were recorded
      every 10 min for five years (January 1983-December 1987). The maximum recorded
      hourly mean irradiance UV radiation was 28 W/m2 and occurred in July, while the
      minimum was 14 W/m2 in December. A steady monthly value of [formula: see text]
      was obtained and equaled 2.9%. A similar trend was found for the monthly
      variation of [formula: see text] and [formula: see text]. Maximum values of 90%
      and 2.6% were recorded in June for Kt and Kv, respectively, while minimum values
      of 35% and 1%, respectively, were obtained in December. A linear correlation was
      obtained between Kv and Kt. These findings were discussed and connected to the
      meteorological events. The results were compared with the regions of Kuwait,
      Bahrain, Dhahran, and Makkah.

PMID- 10902400
TI  - Application of genetic algorithms for the design of ozone control strategies.
AB  - Designing air quality management strategies is complicated by the difficulty in
      simultaneously considering large amounts of relevant data, sophisticated air
      quality models, competing design objectives, and unquantifiable issues. For many
      problems, mathematical optimization can be used to simplify the design process by
      identifying cost-effective solutions. Optimization applications for controlling
      nonlinearly reactive pollutants such as tropospheric ozone, however, have been
      lacking because of the difficulty in representing nonlinear chemistry in
      mathematical programming models. We discuss the use of genetic algorithms (GAs)
      as an alternative optimization approach for developing ozone control strategies.
      A GA formulation is described and demonstrated for an urban-scale ozone control
      problem in which controls are considered for thousands of pollutant sources
      simultaneously. A simple air quality model is integrated into the GA to represent
      ozone transport and chemistry. Variations of the GA formulation for
      multiobjective and chance-constrained optimization are also presented. The paper
      concludes with a discussion of the practically of using more sophisticated,
      regulatory-scale air quality models with the GA. We anticipate that such an
      approach will be practical in the near term for supporting regulatory decision
      making.

PMID- 10902402
TI  - Another great article on osteopathic manipulative treatment.

PMID- 10902401
TI  - Time to take bolder initiative with regard to public accountability.

PMID- 10902403
TI  - Name change diminishes osteopathic medicine's approach.

PMID- 10902404
TI  - Study underscores need to consider multiple factors in debate on physician
      assisted suicide.

PMID- 10902405
TI  - Consortium publishes guidelines to lessen "headache" of treating migraine.

PMID- 10902406
TI  - Opinions and reactions of physicians in New Jersey regarding the Oregon Death
      with Dignity Act.
AB  - Physician-assisted suicide (PAS) was legalized in Oregon in 1997. In the study
      reported here, the authors surveyed a sample of New Jersey physicians with regard
      to Oregon's Death with Dignity Act and to whether similar legislation should be
      enacted in New Jersey. A 49-item questionnaire was sent to 563 physicians in New
      Jersey who were licensed in the specialties of family practice, internal
      medicine, surgery, psychiatry, and obstetrics/gynecology. The questionnaire
      contained sections pertaining to demographics, physicians' attitudes regarding
      PAS, and physicians' opinions on Oregon's Death with Dignity Act. A brief summary
      of the legislation was included in the mailing, which participants were asked to
      read before completing the questionnaire. Of the 191 physicians who responded to
      the survey, 55% agreed with legislation that would legalize PAS, and 59% said
      that a law similar to that enacted in Oregon should exist in New Jersey. However,
      only 47% of respondents indicated that they believed PAS to be consistent with
      the role of a physician to relieve pain and suffering. Slightly more than half of
      respondents indicated that they would refuse to participate in PAS and were
      concerned about issues such as professional and personal liability and the
      potential for abuse. Physicians in New Jersey will require additional
      information, education, and discussion of the ethical and legal implications of
      PAS before a law similar to that in Oregon could be proposed or considered.

PMID- 10902407
TI  - Cardiovascular disease and obstructive sleep apnea: implications for physicians.
AB  - Obstructive sleep apnea (OSA) has been strongly associated with several
      cardiovascular disorders during the past decade, and studies suggested that there
      might be a causal relationship. Recent studies have described several
      pathophysiologic mechanisms that are active in OSA and may participate in the
      development of cardiovascular disorders. Primarily, the repetitive respiratory
      events that occur in OSA cause hypoxia, hypercapnea, arousals, or disrupted sleep
      singly or in combination. These abnormal physiologic events result in increased
      sympathetic outflow, alterations in blood pressure control mechanisms,
      dysfunctional ventilatory regulation, and vascular alterations. As a consequence
      of the relative impact and the genetic predisposition, these pathophysiologic
      alterations may lead to or complicate a wide variety of cardiovascular disorders.
      Frequently, patients who have OSA present with complaints of excessive daytime
      sleepiness, chronic fatigue, snoring, morning headache, and nocturnal arousals.
      Difficult-to-control hypertension, recurrent exacerbations of congestive heart
      failure, and nocturnal angina are common cardiovascular manifestations of
      undiagnosed OSA. This article reviews the major cardiovascular disorders
      associated with OSA and the pathophysiologic mechanisms associated with their
      development.

PMID- 10902408
TI  - Survey of medical ethics in US medical schools: a descriptive study.
AB  - In light of the fact that the incidence of revocation of physician licenses is on
      the rise, a survey was sent to 118 allopathic and 16 osteopathic medical schools
      in the United States to assist in appraising the current resources of US medical
      schools training in bioethics. The author contends that, in view of the
      statistics on increasing actions against postgraduate physicians, the time has
      come to determine what constitutes an effective experience for our students. It
      is hoped that the details of this investigative process will give educators and
      researchers insight into the current state of medical school ethics curriculum
      and increase awareness of the need to address the problems.

PMID- 10902409
TI  - Osteopathic practice. 1903.

PMID- 10902410
TI  - Aa glimpse of Dr. Still's art. 1917.

PMID- 10902411
TI  - Palpatory diagnosis. 1932.

PMID- 10902412
TI  - Male prevalence for reading disability is found in a large sample of black and
      white children free from ascertainment bias.
AB  - Male vulnerability to neurodevelopmental disorders remains controversial. For one
      disorder, reading disability, this sex bias has been interpreted as an artifact
      of referral bias. We investigated sex differences for the incidence of reading
      disability within a large prospective sample of White (N = 16,910) and Black (N =
      15,313) children derived from the National Collaborative Perinatal Project
      (NCPP). Children were classified as having either moderate or severe reading
      disability when they had reading scores lower than 1.5 or 2.0 standard errors of
      prediction, respectively, given their age and intelligence. Reading disability
      was about twice as common in boys than girls (p < .001), irrespective of race,
      severity of disability, or exclusion of children with attentional disturbances or
      high activity levels. We conclude that there is a clear sex bias toward males for
      the incidence of reading disabilities.

PMID- 10902413
TI  - Attention in HIV-infected children: results from the Hemophilia Growth and
      Development Study.
AB  - Attentional functioning was examined in three groups of 7- to 19-year-old male
      participants with hemophilia: (1) HIV seronegative controls (HIV-, N = 66), (2)
      HIV seropositive participants with CD4+ lymphocyte counts greater than or equal
      to 200 (HIV+ CD4+ > or = 200, N = 79), and (3) severely immune suppressed HIV
      seropositive participants (HIV+ CD4+ < 200, N = 28). Two measures sensitive to
      attention deficits were used: the Continuous Performance Test (CPT) and the Span
      of Apprehension (Span). On the CPT, there was a decrement in attention in both
      HIV+ groups, as indexed by an increase in false alarm rate from Block 1 to Block
      3, that was not present in the HIV- group. The longer the HIV+ children were
      required to sustain attention to the CPT, the more they responded to the
      incorrect stimulus. This effect decreased as age increased. Span percent correct
      and latency to correct were associated with the presence of a premorbid history
      of intracerebral hemorrhage, but were not sensitive to HIV status or degree of
      immune suppression in the HIV+ children, suggesting morbidity related to
      hemophilia. The remaining CPT and Span variables--hit rate, sensitivity, latency,
      percent correct, and latency to correct--showed the expected associations with
      age, but none showed conclusive associations with HIV status or immune
      suppression in the HIV+ participants.

PMID- 10902415
TI  - The Frontal Behavioral Inventory in the differential diagnosis of frontotemporal
      dementia.
AB  - A personality and behavioral disorder is an important and defining feature of
      frontal lobe dementia (FLD) or frontotemporal degeneration (FTD). The diagnosis
      usually depends on the progressive development of various behavioral symptoms
      rather than a set of neuropsychological measures. Quantification of the
      personality-behavior disorder is important for standardizing the diagnosis. An
      inventory was constructed to capture the major positive and negative behaviors
      and personality change, and it was administered prospectively to caregivers of
      108 patients in a cognitive neurology clinic, at the time of first diagnostic
      assessment. The prevalence and extent of behavioral abnormality was quantitated
      in the clinic population of FLD, vascular dementia (VaD), Alzheimer's disease
      (AD), primary progressive aphasia (PPA), and depressive disorder (DD) patients.
      The mean scores of FLD patients were significantly above all other groups. Scores
      in VaD were also higher than in AD, PPA, and DD. Interrater reliability (Cohen's
      kappa of .90) and item consistency (a Cronbach alpha of .89) were both high.
      Perseveration, indifference, inattention, inappropriateness, and loss of insight
      rated highest in FLD, significantly different from all other groups. Apathy,
      aspontaneity, inflexibility, disorganization, impulsivity, personal neglect, and
      poor judgment were also significantly higher in FLD. Discriminant function
      correctly classified 92.7% versus all other patients (NON-FLD) in the study. A
      total of 18.8% of VaD patients were misclassified as FLD. Indifference, alien
      hand, and inappropriateness were the highest discriminant functions.
      Perseveration and verbal apraxia were important discriminatory items for FLD and
      PPA, respectively. The FBI is a standardized behavioral inventory useful to
      diagnose FLD, to differentiate it from other dementias, and to quantify the
      behavior disorder.

PMID- 10902414
TI  - Horizontal line bisections in upper and lower body space.
AB  - Whereas the ventral cortical visual stream is important in object recognition,
      the dorsal stream is specialized for spatial localization. In humans there are
      also right and left hemisphere asymmetries in visual processing: the left
      hemisphere being more important in object recognition and the right in specifying
      spatial locations. Based on these dorsal-ventral and right-left where-what
      dichotomies, one would expect that the dorsal right hemisphere systems would be
      most activated during spatial localization tasks, and this activation may induce
      a leftward spatial bias in lower space. To determine if visual stimuli in upper
      and lower body space evoke different hemispheric activation, we had 12 normal
      participants bisect horizontal lines above and below eye level. Participants
      erred leftward in lower body space relative to upper body space (M = 1.3345 mm
      and 0.4225 mm, respectively; p = .011). In upper body space, bisection errors did
      not differ from zero, but in lower body space, errors tended to deviate leftward
      (M = 1.3345 mm, differs from null hypotheses at p = .0755). Our results are
      consistent with dorsal stream/right hemisphere activation when performing a
      spatial localization task in lower versus upper body space.

PMID- 10902416
TI  - Improvement or simply practice? The effects of twenty repeated assessments on
      people with and without brain injury.
AB  - Measuring recovery of function may mean testing the same individual many times, a
      procedure that is inevitably open to improvement due to learning on the specific
      tests rather than recovery per se. This is particularly likely to be an issue
      with measures of memory performance. We therefore studied the performance of
      normal and brain-injured people across 20 successive test sessions on measures of
      orientation, simple reaction time, forward and backward digit span, visual and
      verbal recognition, word list learning and forgetting, and on three semantic
      memory measures, namely, letter and category fluency and speed of semantic
      processing. Differences in overall performances between the two groups occurred
      for all tests other than orientation, digit span forward, and simple reaction
      time, although the tests differed in their degree of sensitivity. The tests
      varied in the presence or absence of practice effects and in the extent to which
      these differed between the two groups. Data are presented that should allow
      investigators to select measures that are likely to optimize sensitivity while
      minimizing possible confounding due to practice effects.

PMID- 10902417
TI  - Fitness to drive in older drivers with cognitive impairment.
AB  - This paper is a literature review on assessment of fitness to drive in older
      drivers with cognitive impairment. Early studies on dementia and driving
      generally failed to distinguish between safe and unsafe drivers on the basis of
      cognitive test performance. Predictive studies demonstrated that cognitively
      impaired persons as a group perform significantly worse than controls on both
      neuropsychological and driving measures. A high prevalence of cognitive
      impairment was found in groups of older drivers involved in traffic accidents and
      crashes. However, a large range in neuropsychological test scores has been found.
      Low to moderate correlations could be established between neuropsychological test
      results and on-road driving performance, making it difficult to discriminate
      between cognitively impaired subjects who are fit or unfit to drive. The review
      concludes with a discussion of methodological difficulties in the field of
      dementia and driving, including participant selection, the choice of
      neuropsychological tests, and the operationalization of driving performance.

PMID- 10902418
TI  - A history of the International Neuropsychological Society: the early years (1965
      1985).
AB  - A history of the early years (1965-1985) of the International Neuropsychological
      Society (INS) is presented. Themes than run through these years--such as the need
      for an organizational structure, attempts to make the Society truly
      international, and the involvement of the membership, especially, the "younger"
      members, in governance--are clearly evident. After a somewhat shaky start, the
      Society came of age toward the end of this formative 20-year period.

PMID- 10902419
TI  - Prevalence of ocular diseases in South Carolina.

PMID- 10902420
TI  - Incidence and prognostic significance of carotid stenosis in a cardiac rehab
      population. Results of the Simvastatin Carotid Artery Stenosis Study (Z-CASS).

PMID- 10902421
TI  - Carotid endarterectomy and carotid stenting: a position paper from the South
      Carolina Vascular Surgery Society.

PMID- 10902422
TI  - Depression comes in many disguises to the providers of primary care: recognition
      and management.
AB  - Depression is encountered frequently in the primary care setting. Its appearance
      is dominated by the physical symptoms of the syndrome. This factor, when combined
      with the residual stigma that mitigates against acceptance of the diagnosis,
      probably accounts for how often the diagnosis is missed. The depressive illnesses
      are serious, disrupting occupational and social functioning to a significant
      degree. They are life-threatening for some in the short-term, but for many more
      over a lifetime, as depression is more often recurrent or chronic than a one time
      experience. With a psychiatric nomenclature now available that is user-friendly,
      screening tests that are available and easy to administer, and treatments that
      are successful, it is important that the physician learn to recognize and manage
      this common set of problems. Depression is typically co-morbid with serious
      medical illness, and often co-morbid with complicating emotional disorders. It
      may appear in a form that takes a bipolar course, including episodes of mania and
      hypomania. The physician in practice must decide which patients with depression
      he or she will treat, and who to refer for specialty care. The SSRI anti
      depressants are usually the frontline treatment of choice. Bipolar, treatment
      resistant, and difficult patients with co-morbid psychiatric illnesses should be
      referred to psychiatrists. It is valuable for the physician to have psychiatrists
      he or she knows to facilitate consultation, communication and coordination. The
      value of brief psychotherapy in the treatment of a depressive episode underlines
      the need for a psychiatrist with whom the physician can work collaboratively. The
      depressed patient presents the physician with a situation in which he or she can
      make a positive difference in the life of a person and his or her family. The
      need to model and teach the treatment of depression in primary care is evident,
      with the likelihood that this will be the arena in which these patients will
      continue to receive care.

PMID- 10902423
TI  - Y2K.4. Virtues and values.

PMID- 10902424
TI  - Births, marriages, divorces, and deaths: provisional data for July 1999.

PMID- 10902426
TI  - [The new juridical procedure in law 1/4/1999 no. 91 relative to organ procurement
      for therapeutic transplantation].

PMID- 10902425
TI  - [Aggressive lymphomas: a convenient concept or an anatomo-pathological reality?].

PMID- 10902427
TI  - [Application of PCR in the diagnosis of B-type non-Hodgkin's lymphomas in
      cytological specimens from fine-needle aspiration].
AB  - The application of PCR to detect monoclonality at the immunoglobulin heavy chain
      gene locus in FNA cytologic specimens was evaluated. MATERIALS AND METHODS:
      Immunoglobulin heavy chain gene rearrangement analysis was performed by a nested
      PCR for the VDJ region on 27 lymph nodes FNA paraffin embedded by cell blocking
      technique specimens (1 suspicious of NOS lymphoma, 1 Hodgkin's disease, 6 B cell
      non Hodgkin's lymphomas, 10 reactive hyperplasias). RESULTS: A monoclonal band
      was seen in 13 of 17 suspicious or positive malignant cases. The other 4
      specimens gave a policlonal pattern. Specimens from reactive lymph nodes produced
      policlonal bands in 8 cases, no product in 1 case and 1 specimen gave a
      monoclonal band. When needed, the results of PCR examinations were compared with
      the subsequent histologic evaluation of the same lymph-node. CONCLUSIONS: From
      our experience we can see that clonal analysis by PCR based IgH gene
      rearrangement analysis can be applied to FNA material and can be useful in
      diagnosis.

PMID- 10902428
TI  - [The cervico-vaginal cytology workload. A complex task in planning laboratory
      activities].
AB  - Measurement of professional work efforts are desired by health care
      administrators as a means of comparing the efficiency of the laboratory
      activities in an attempt to predict proper staffing levels and funding. In view
      of the complexity of measuring pathology workload, it is not surprising that the
      evaluation of this effort has never been adequately quantitated and that, as a
      consequence, literature data are scant. We reviewed all available information on
      cervical cytology workload. Most data refer to cytoscreener workload while very
      few indications concerning the cytopathologist's performance can be obtained. The
      vast majority of reported figures derive from the English literature and show
      extreme variability: for cytoscreener/cytotechnologist, the workload figures are
      between 3,000-15,000/year, 40-150/day and 3-20/hour. In addition, data are
      scarcely comparable since the true "object" of the workload measurement is not
      always evident: just Pap-test microscopic screening or pre- and post-analytical
      procedures too? In the Italian milieu , a reasonable cytoscreener workload would
      range from 6 slide/hour (i.e. 45-50/day or 10,000/year) if the duty is limited to
      the screen only, to 4 slide/hour (i.e. 30-35/day or 7,000/year) for people
      involved in slide preparation or ancillary duties. For both events, upper and
      lower workload limits are suggested. We conclude that professional attention must
      be given to determine appropriate workloads in order to minimize suboptimal
      performance and improve the cost-effectiveness of laboratory activities.

PMID- 10902429
TI  - Effects of oral contraceptives in vaginal cytology.
AB  - Many literature studies have shown that long-term use of oral contraceptives (OC)
      is associated with lack of protection of the epithelium of the uterine cervix.
      Forty-five patients, from 18 to 35 years old, users of two contraceptive
      formulations, of different estrogenic concentration, took part in this study as
      volunteers to evaluate the predisposition of the cervix to pathologies. The
      results found before OC use were 11% of Chlamydia trachomatis infection and 13%
      of HPV infection. These pathologies were correctly treated and after 5 months of
      OC use we found total remission of Chlamydia trachomatis infection and 4% of
      persistent HPV infection. These data lead us to conclude that the OC studied here
      interfered very little with the presented pathologic results. The risk factors
      that we considered relevant were: 1) age group (the patients that presented HPV
      and C. trachomatis infections were young university students); 2) lifestyle (most
      patients certified that they did not combine the use of barrier contraceptives
      with the use of OC); 3) multiple sexual partners; 4) low socioeconomic condition.

PMID- 10902430
TI  - [Lympho-epithelial carcinoma (malignant lympho-epithelial lesions) of the parotid
      gland. Description of a case with detection of EBV by in situ hybridization].
AB  - The authors describe a case of malignant lymphoepithelial lesion (MLEL), commonly
      referred to as lymphoepithelial carcinoma of parotid gland, that is a very rare
      tumour. There is a relatively high incidence in Eskimos of Alaska and Greenland,
      but some cases are described in natives of south China. The immunophenotypic
      profile and histopathological aspect of this neoplasm are discussed, and the
      differential diagnosis in regard to other primitive or metastatic tumours of
      parotid is also considered. In our case a diffuse positivity of epithelial
      neoplastic cells for EBV genome was found using in situ hybridization. The
      possible role of EBV in the ethiopathogenesis of this rare lesion is herein
      discussed.

PMID- 10902431
TI  - [Hyperkeratosis follicularis et parafollicularis in cutem penetrans (Kyrle's
      disease). Description of a case].
AB  - A case of hyperkeratosis follicularis et parafollicularis in cutem penetrans
      Kyrle's disease in a 41-year-old woman is described. It was a recurrence of a
      lesion surgically removed and originally diagnosed as invasive squamous cell
      carcinoma. Kyrle's disease is a rare dermatosis and should not be confused with
      neoplastic conditions i.e. squamous cell carcinoma. Pathologists should be aware
      of such conditions in order to avoid misdiagnosis, which can imply over treatment
      for the patient.

PMID- 10902433
TI  - [In Process Citation]

PMID- 10902432
TI  - [Malignant glial tumor with skeletal muscle differentiation. Description of a
      case].
AB  - A case of CNS gliomyosarcoma, in a 71-year-old female with skeletal muscle
      differentiation is presented. The tumor was composed by two cell types: one
      showed features typical of glial cells, the other was constituted by elements
      having immunohistochemical positivity with desmin, sarcomeric actin, myoglobin
      and myogenin antisera. It is postulated an origin from a cell capable of dual
      differentiation.

PMID- 10902434
TI  - [PCNA and viral hepatitis C].

PMID- 10902435
TI  - [Nodular hepatocellular lesions. Guidelines and minimal diagnostic criteria for
      gastrointestinal histopathological diagnosis. Gruppo Italiano Patologi
      dell'Apparato Digerente].

PMID- 10902436
TI  - [On the trail of vampires. A brief history of postmortem phenomena].

PMID- 10902438
TI  - A viscoelastic analysis of the tensile weakening of deep femoral head articular
      cartilage.
AB  - Articular cartilage from below the surface of the femoral head of the hip joint
      shows a profound age-dependent weakening in its tensile mechanical properties.
      This ageing is also associated with a reduced viscoelastic response in the older
      tissue. A constitutive model of the viscoelastic behaviour of deep articular
      cartilage (as discussed by Egan in 1988) is used to generate a graphical pattern
      which represents the mechanical behaviour. This constitutive approach suggests
      that the tensile weakening of the older cartilage is due to an age-related
      reduction in the recruitment of load-carrying structures as the tissue is
      deformed. The viscoelastic constitutive model also predicts a reduction in the
      tensile strength of deep articular cartilage with rate of deformation. This
      prediction is supported by experimental fracture stress data. A weakening of the
      tensile integrity of the microstructure of articular cartilage could make the
      tissue less able to sustain normal compressive physiological loading without
      damage and thus make the tissue more susceptible to osteoarthritic degeneration.
      The constitutive approach indicates that the weakening of the older tissue may be
      related to changes within the microstructure which determine how applied
      mechanical energy is stored and dissipated.

PMID- 10902437
TI  - Simplified motion and loading compared to physiological motion and loading in a
      hip joint simulator.
AB  - Two wear tests were conducted using the Durham Hip Joint Wear Simulator to
      investigate the effects of simplified motion and loading on ultra-high molecular
      weight polyethylene (UHMWPE) acetabular cup wear rates. Bovine serum was used as
      a lubricant and a gravimetric technique was used to measure wear. The first wear
      test duration was 7.1 x 10(6) cycles and investigated the effect of simplified
      loading. This was achieved by using full physiological motion and loading for the
      first 5 x 10(6) cycles of the test, then physiological motion with simplified
      loading for the final 2.1 x 10(6) cycles of the wear test. The UHMWPE acetabular
      cup wear rates using full physiological motion and loading were 32.2 and 51.7
      mm3/10(6) cycles against zirconia and CoCrMo femoral heads respectively. Using
      simplified loading the cup wear rates were 30.1 and 49.2 mm3/10(6) cycles against
      zirconia and CoCrMo respectively which was not significantly different from wear
      rates with physiological loading. The effect of simplified motion was
      investigated in a second wear test of 5.0 x 10(6) cycles duration. Physiological
      loading was applied across the prosthesis with physiological motion in the
      flexion/extension plane only. Mean wear of the acetabular component dropped to
      0.197 mm3/10(6) cycles. The surfaces of all the acetabular cups were subject to
      gross examination, optical microscopy and scanning electron microscopy. No
      notable difference was observed between the cups subjected to physiological
      motion and loading and those subjected to simplified loading. The cups worn with
      a single plane of motion had a much smaller worn area and a notable difference in
      surface features to the other cups. Simplifed loading is therefore an acceptable
      simplification in simulator testing but simplifying motion to the
      flexion/extension plane axis only is unacceptable.

PMID- 10902439
TI  - Comparison of gas plasma and gamma irradiation in air sterilization on the
      delamination wear of the ultra-high molecular weight polyethylene used in knee
      replacements.
AB  - Early failure of knee replacements is thought to be due to the combination of
      sterilization by gamma irradiation in air and the high cyclic stresses that they
      endure during use. Such failures are shown through delamination and permanent
      deformation of the ultra-high molecular weight polyethylene (UHMWPE) component.
      This study investigated whether gas plasma sterilization, as an alternative to
      gamma irradiation in air, would give better performance after ageing in a knee
      replacement using a metal pin on polymer plate wear test. Fourier transform
      infrared (FTIR) analysis was performed on the components to assess oxidation
      levels and a finite element stress analysis model is presented to estimate strain
      at failure in the UHMWPE. Delamination occurred in the majority of the gamma
      irradiated plates but did not occur in any of the gas-plasma-sterilized plates.
      The FTIR analysis showed that the plates gamma irradiated in air were highly
      oxidized when compared with the gas-plasma-sterilized plates. Plastic strain at
      failure was determined for the gamma-irradiated plates and found to be less than
      2.4-14 per cent.

PMID- 10902440
TI  - A moment-based technique for the automatic spatial alignment of plantar pressure
      data.
AB  - Plantar pressure measurements have many potential clinical applications in the
      field of orthopaedics. However, the only current routine clinical application of
      pedobarography is for the identification of high pressure zones in diabetic
      patients with neuropathy who are at risk from foot ulceration. For pedobarography
      to become a routine clinical tool in orthopaedics, a thorough knowledge of normal
      plantar pressure distributions would be required. To date, no large scale studies
      to define population norms have been conducted, probably because of the high cost
      associated with analysing large quantities of plantar pressure data. Plantar
      pressure distributions display a high step-to-step variation and, therefore, it
      is necessary to conduct multiple trials. Comparison between these trials is
      difficult, somewhat subjective, and slow, because it must be conducted manually.
      The present authors have developed a technique to align automatically the spatial
      components of a series of datasets. The technique then allows predefined
      parameters to be automatically extracted from the data, hence greatly reducing
      analysis time. The authors believe that not only does the technique make large
      scale studies economically viable but that it could also form the basis for
      expert systems for the diagnosis of foot pathologies and the prescription of
      orthoses.

PMID- 10902442
TI  - The variation in the orientations and moment arms of the knee extensor and flexor
      muscle tendons with increasing muscle force: a mathematical analysis.
AB  - The orientations and moment arms of the knee extensor and flexor muscle tendons
      are evaluated with increasing values of muscle force during simulated isometric
      exercises. A four-bar linkage model of the knee in the sagittal plane was used to
      define the motion of the joint in the unloaded state during 0-120 degrees
      flexion. The cruciate and collateral ligaments were represented by arrays of
      elastic fibres, which were recruited sequentially under load or remained buckled
      when slack. A bi-articular model of the patello-femoral joint was used. Simple
      straight-line representation was used for the lines of action of the forces
      transmitted by the model muscle tendons. The effects of tissue deformation with
      increasing muscle force were considered. During quadriceps contraction resisted
      by an external flexing load, the maximum change in moment arm of the patellar
      tendon was found to be 2 per cent at 0 degree flexion when the quadriceps force
      was increased tenfold, from 250 to 2500 N. The corresponding maximum change in
      orientation of the tendon was 3 degrees at 120 degrees flexion. During hamstrings
      contraction resisted by an external extending load, the maximum change in moment
      arm of the hamstrings tendon was 8 per cent at 60 degrees flexion when the
      hamstrings force was increased tenfold, from 100 to 1000 N. During gastrocnemious
      contraction, the corresponding maximum change for the gastrocnemious tendon was 3
      per cent at 0 degree. The orientations of the flexor muscle tendons in this range
      of force either remained constant or changed by 1 degree or less at any flexion
      angle. The general trend at any flexion angle was that, as the muscle force was
      increased, the moment arms and the orientations approached nearly constant
      values, showing asymptotic behaviour. It is concluded that experimental
      simulations of knee muscle action with low values of the externally applied load,
      of the order of 50 N, can provide reliable estimates of the relationships between
      muscle forces and external loads during activity.

PMID- 10902441
TI  - Limitations in the use of median frequency for lung sound analysis.
AB  - The aim of this paper is to investigate methods of standardizing lung sound
      analysis, with a view to supplementing traditional spirometric air flow
      measurements to help in the diagnosis of asthma and to provide a measure of the
      effectiveness of treatment. Lung sounds were measured in nine patients with
      asthma and five control subjects, alongside air flow measurements of forced
      expiratory volume (FEV1) and forced vital capacity (FVC). The patients were
      administered the bronchodilator, salbutamol, to assess how effective these
      measurement techniques were for quantifying its effect. The results agree with
      previous studies, that analysis of lung sounds is a potentially useful tool for
      indicating air flow changes. The results, however, also demonstrate that the
      emerging standard of 'F50' or 'median frequency' should be treated with great
      caution because of its high sensitivity to the measurement frequency range. F50
      is very unlikely to provide a reliable single indicator of lung condition.

PMID- 10902443
TI  - Biomechanical simulation of an amputated forearm with and without a prosthesis.
AB  - In this study a computer simulation was developed for analysing the performance
      of a below-elbow amputated forearm, with and without a prosthesis. The upper
      extremity was represented in terms of two rigid bodies, the arm and the forearm.
      Five muscles, three elbow flexors and two elbow extensors, were included in the
      model. The muscle model used was the five-component model, including the
      contractile, parallel, series and viscous elements and the muscle mass. Dynamic
      and static simulations were conducted, with and without prosthesis, to study
      parametrically the effects of stump length, tendon distal transfer, tendon or
      muscle shortening and muscle physiological cross-sectional area. The performance
      measures which were the most affected included flexion moment of the forearm
      about the elbow, muscle moment, force in the joint, flexion rate and mechanical
      energy. The simulation presented an interesting case when the amputation site is
      more proximal than the anatomical insertion point of a muscle, necessitating
      shortening of the muscle to avoid the situation where it exerts no force. It was
      also found that, of the changeable parameters, the most beneficial changes in the
      forearm parameters for improved dynamic performance were: (a) tendon distal
      transfer and (b) increase of the muscle cross-sectional area, the latter
      achievable by means of physical training.

PMID- 10902444
TI  - Determination of the major dimensions of femoral implants using morphometrical
      data and principal component analysis.
AB  - This paper describes the work that leads to the establishment of a set of major
      parameters for the design of symmetrical prosthetic implants for the Asian
      population. In the study, 62 sets of femurs harvested from cadavers were used.
      The morphometrical data obtained are compared with known results and found to be
      in good agreement with Asian knees. Subsequently, the data are treated and
      analysed using the principal component analysis, a statistical technique for
      analysing multivariate data. The analysis has resulted in the establishment of
      the major design parameters for six different sizes of femoral implants. Details
      of the analysis are presented. The major parameters obtained in this work are
      compared with those of existing implants. Results of the comparison are
      presented. The relationship between the anterio-posterior and medio-lateral
      dimensions is also examined and reported.

PMID- 10902445
TI  - Numerical investigation of fixed orthodontic brackets.
AB  - This paper presents the results of investigations into the mechanical behaviour
      of fixed orthodontic brackets. Special attention has been paid to the detailed
      modelling of the interface between the bracket base and an adhesive by which
      attachment is made to the tooth surface. Properties of this interface were taken
      as design parameters with the aim of investigating their influence on the stress
      field induced during bracket removal at the end of the treatment. Stress-strain
      analysis was performed using a finite element program developed in-house.

PMID- 10902446
TI  - Development of surgical instruments for implanting a flexible fixation device for
      the lumbar spine.
AB  - A new flexible fixation device for the lumbar spine has been developed. This
      paper describes the development and evaluation of two surgical instruments
      required for implanting this device. Prototypes were designed, manufactured and
      then evaluated for use in surgery. Further evaluation was performed, if
      necessary, and the design finalized, in accordance with BS EN 12011. This process
      involved close collaboration between engineers and surgeons.

PMID- 10902447
TI  - [A century of subarachnoid anesthesia in Spain].

PMID- 10902448
TI  - [Multivariate study of risk factors for arterial hypotension in pregnant patients
      at term undergoing Caesarean section under subarachnoid anesthesia].
AB  - OBJECTIVES: The most common and potentially dangerous complication of spinal
      anesthesia for cesarean section is arterial hypotension. The aim of this study
      was to analyze maternal and gestational factors that might affect risk of
      arterial hypotension in full-term parturients undergoing cesarean section.
      MATERIAL AND METHOD: We enrolled full-term parturients scheduled for elective
      cesarean section under spinal anesthesia. Spinal puncture was performed at L2-L3
      using an atraumatic Sprotte-type needle. We administered 12.5 mg of hyperbaric
      0.5% bupivacaine and 12.5 micrograms of fentanyl. Arterial hypotension was
      defined as a decrease in systolic pressure of at least 20% or a decrease to a
      pressure below 100 mmHg. Multivariate analysis was performed to identify factors
      related to the presentation of hypotension appearing in the interval between
      spinal puncture and birth. RESULTS: The incidence of arterial hypotension was
      33.3%. Statistical analysis revealed that integrity of the amniotic sac, parity
      and elective cesarean were significantly associated with a higher incidence of
      arterial hypotension (p < 0.03). CONCLUSIONS: Identifying risk for multiparous
      parturients with intact amniotic sacs scheduled for elective cesarean can be
      worthwhile if greater preventive measures are taken in such patients to reduce
      the incidence and intensity of arterial hypotension.

PMID- 10902449
TI  - [Comparative study between 5% prilocaine and 2% mepivacaine by the subarachnoid
      route in transurethral resections].
AB  - OBJECTIVE: To compare the duration of spinal block with 5% prilocaine and 2%
      mepivacaine in short procedures for transurethral resection and to assess
      possible complications in the immediate postoperative period. MATERIAL AND
      METHODS: Fifty-seven patients scheduled for transurethral resection of the
      prostate or a vesical tumor. Patients were ASA I-III, over 55 years of age and
      randomly assigned to two groups to receive 5% prilocaine (1 mg/kg, n = 27) or 2%
      mepivacaine (0.8 mg/kg, n = 30). We collected data on anesthetic technique,
      levels of extension of motor and sensory blockades, duration of blockades and
      complications within the first 24 hours after surgery. RESULTS: Demographic data,
      ASA classification and duration of surgery were similar in both groups. We found
      statistically significant differences (p < 0.05) in duration of sensory blockade
      (120.92 +/- 36.21 min with prilocaine and 145.83 +/- 35.81 min with mepivacaine)
      and in motor blockade (106.29 +/- 38.16 min with prilocaine and 133.16 +/- 42.21
      min with mepivacaine). Five cases of hypotension and 4 of bradycardia occurred in
      each group and one patient in the mepivacaine group suffered slight postoperative
      cephalea. CONCLUSIONS: Both local anesthetics offer good surgical conditions with
      hemodynamic stability and few complications. The duration of sensory and motor
      blockade is shorter with prilocaine than with mepivacaine, making prilocaine more
      appropriate for short interventions.

PMID- 10902450
TI  - [Subarachnoid anesthesia: 100 years of an established technique].
AB  - Over the 100 years since the introduction of spinal anesthesia into clinical
      practice, this technique, like most others, has enjoyed varying degrees of
      popularity. The attraction of spinal anesthesia is easy to identify: a relatively
      simple technique is used to inject a very small amount of drug into a readily
      identifiable body compartment to provide deep anesthesia. However, the apparent
      simplicity of spinal anesthesia is as much as weakness as a strength, given that
      the technique can be put to use with relatively little understanding of its
      problems, which are what underlie the shifts in popularity that spinal anesthesia
      has suffered over the years. In addition to reviewing the history of spinal
      anesthesia and the local anesthetics and adjuvant drugs administered by this
      route, we discuss single-dose and continuous spinal injection, combined spinal
      epidural technique, and spinal anesthesia for outpatient settings. The problems
      typical of dural puncture and placement of local anesthetics and adjuvant drugs
      into the intrathecal space are also reviewed.

PMID- 10902451
TI  - [Combined subarachnoid-epidural technique for obstetric analgesia].
AB  - Combined spinal-epidural blockade for labor pain has enjoyed increasing
      popularity in obstetric anesthesia. The usual procedure is to use a single space
      and a single needle for dural puncture, inserting a spinal needle through an
      epidural needle followed by insertion of a catheter. A small dose of one or
      several substances (usually a lipophilic opioid and a local anesthetic) is first
      injected in the intrathecal space to provide rapid, effective analgesia with
      minimal muscle blockade. The epidural catheter is used if labor lasts longer than
      the spinal block, if the spinal block is insufficient, or in case of cesarean
      section. Combined spinal-epidural blockade is a safe, valid alternative to
      conventional epidural analgesia and has become the main technique for providing
      obstetric analgesia in many hospitals. The most widely-recognized advantage of
      the technique is high maternal satisfaction with rapid and effective analgesia.
      Mobility of the lower extremities is preserved and the mother is often able to
      walk. Because opioids are injected into the intrathecal space and because the
      technique is more invasive than standard epidural analgesia, the potential risk
      to mother and fetus increases.

PMID- 10902452
TI  - [Centenary of spinal anesthesia in Spain: first steps (1899-1904)].
AB  - With the aim of commemorating the centennial of the first spinal anesthesia in
      Spain, we review the process followed during the early phase of application of
      the technique, the period associated with spinal injection of cocaine, which was
      the only anesthetic agent used. We describe the first trials, the influence of
      the Paris Congress of 1900 in spreading interest in the technique, the varied
      degree of acceptance by Spanish authors, and the gradual uneasiness with the
      procedure that arose as a result of accidents. A look at reports by Pi Sunyer and
      Raventos concerning possible toxic effects on the central nervous system close
      this overview of the earliest times of spinal anesthesia in Spain.

PMID- 10902453
TI  - [Isobaric 2% lidocaine in continuous subarachnoid anesthesia using
      microcatheters].
AB  - The objective in the study of the clinical effect of isobaric 2% lidocaine for
      continuous spinal anesthesia with a microcatheter technique. Nine consecutive
      patients undergoing lower abdominal surgery under spinal anesthesia were
      enrolled. We inserted 27 G catheters through 22 G Sprotte (Intralong) needles to
      administer 20 mg of isobaric 2% lidocaine followed by successive doses of 10 mg
      until the required level of anesthesia was reached. Repeated injections of 10 mg
      were given during surgery whenever the level of anesthesia fell as much as one
      metamere, possibly permitting pain to appear. We recorded hemodynamic variables,
      level of anesthesia and motor block, as well as complications during and after
      surgery. The technique was used with nine patients, for whom the mean presurgical
      dose was 32.3 +/- 9.2 mg and the mean total dose was 51.3 +/- 25.3 mg. However,
      the protocol for administering the local anesthetic was suspended in three
      patients due to difficulty in maintaining the achieved level of anesthesia, as
      repeated injections were required, with consequent patient discomfort. In these
      patients relatively high levels of blockade were required and surgery lasted
      longer than one hour. The protocol followed with isobaric 2% lidocaine was not
      effective for continuous spinal anesthesia with microcatheters because of
      difficulty of maintaining level of anesthesia.

PMID- 10902454
TI  - [Bacterial meningitis after subarachnoid anesthesia].

PMID- 10902455
TI  - [Aseptic meningitis after intradural anesthesia].

PMID- 10902456
TI  - [Differential diagnosis of postoperative meningitis after subarachnoid
      anesthesia].

PMID- 10902457
TI  - [Headache following dural puncture refractory to caffeine].

PMID- 10902458
TI  - [Long QT syndrome and regional anesthesia. Apropos of a case].

PMID- 10902459
TI  - [Enantiomers and local anesthetics].

PMID- 10902460
TI  - [Cholestatic hepatopathy: primary biliary cirrhosis].
AB  - Primary biliary cirrhosis is a cholestatic autoimmune disease of the liver. Its
      prevalence has significantly increased over the last seven years, therefore it
      can no longer be considered to be a rare liver disease. It is seen in 94/100,000
      women older than 40 years. The treatment consists of administration of
      ursodeoxycholic acid, better therapy results seem to be achieved by combining
      UDCA with immunosuppressants. While UDCA-monotherapy proved to extend the time
      until liver transplantation and thus leads to life prolongation, this could not
      yet be shown for the combination therapies. Therapy of the often agonizing
      pruritus and of osteoporosis remains problematic. Frequently this can only be
      managed by the combination of several treatment measures.

PMID- 10902461
TI  - [Hepatitis C--standard therapy].
AB  - Infection with the hepatitis C virus leads to chronic hepatitis in the majority
      of patients. Diagnosis is based on the presence of anti-HCV antibodies and
      confirmed by positive HCV RNA. The natural course of the disease is slow.
      Cirrhosis is found in a minority of patients two decades post infection.
      Nevertheless, cirrhosis is much more frequently observed than in patients with
      hepatitis B infection. Treatment of choice is interferon-alpha. Today combination
      with ribavirin is recommended for most patients. In combination therapy the
      sustained response rate six months after stop of treatment is about 40% in naive
      patients with respect to virus elimination. In patients treated with high doses
      of interferon-a for one year the sustained response rate is comparable. The
      response rate is higher in patients with HCV infections of non-1 genotype and in
      patients with lower virus titers, e.g. less than 2 Mill. genome equivalents per
      ml. Interferon-a treatment also leads to an improvement of liver histology. Necro
      inflammatory scores are reduced. It has also an antifibrogenic effect.
      Progression of fibrosis is reduced. The antiproliferative effect of interferon-a
      leads a lower rate of hepatocellular carcinomas, which has been demonstrated in
      several retrospective studies. In patients with Child A cirrhosis the time till
      decompensation is delayed. Because of the slow progression, the relatively low
      response rate and the adverse events of interferon-a and ribavirin treatment
      should be instituted on an individual base depending on host factors such as age,
      co-morbidity and stage of liver disease.

PMID- 10902462
TI  - [Hepatocellular carcinoma: percutaneous ethanol injection/transarterial
      chemoembolization/radiofrequency thermoablation].
AB  - In the majority of patients hepatocellular carcinoma (HCC) is associated with
      liver cirrhosis. Advanced or decompensated liver cirrhosis, comorbidity and
      multicentricity make 70-80% of HCCs inoperable at the time of diagnosis.
      Therefore, percutaneous ethanol injection (PEI) and radiofrequency thermal
      ablation (RFTA) are non-surgical therapeutic options for patients with small
      HCCs. In patients with advanced tumor stage transarterial chemoembolization
      (TACE) and its variants showed no survival benefit on the basis of randomized
      trials. In several studies, however, combined treatment strategies like TACE and
      PEI or RFTA after occlusion of tumor blood supply in the treatment of advanced
      HCC seems to result in a survival benefit. All HCC patients should be included in
      randomized treatment studies.

PMID- 10902463
TI  - [Abdominal ultrasound diagnosis].
AB  - The doppler sonography is an important tool in the diagnosis of liver diseases,
      even by using new techniques like the power doppler. There are a lot of
      indications for the evaluation of the hepatic vessels. Apart from the diagnosis
      of portal hypertension in liver cirrhosis a portal vein thrombosis should be
      detected or excluded in cases of new or refractory ascites. The Budd-Chiari
      syndrome is another important indication. Focal liver lesions can have
      characteristic findings in doppler sonography, but an exact differentiation of
      liver tumors is not possible. But doppler sonography even using the power doppler
      technique is be used more and more in hepatocellular carcinoma to evaluate the
      response to treatment with chemoembolization, radiofrequency thermoablation or
      percutaneous ethanol injection. The accuracy is compatible to angiography and
      computer-tomography.

PMID- 10902464
TI  - The validity of reported tobacco use.

PMID- 10902465
TI  - Reflections on reading Abortion in the Developing World.

PMID- 10902467
TI  - Kangaroo care in Port Moresby, Papua New Guinea.
AB  - Kangaroo care is a simple and highly practical method of care of the low
      birthweight newborn which has been shown in some studies to significantly improve
      survival. We describe the introduction of 'kangaroo care' to the special care
      nursery at Port Moresby General Hospital, discuss the problems encountered and
      attempt to assess its impact in a 1-year retrospective study, during which it was
      associated with a reduction in hypothermia and an increased rate of weight gain.

PMID- 10902466
TI  - Major amputations in Nigeria: a plea to educate traditional bone setters.
AB  - A study was made of 100 major amputations performed on 96 patients in two
      regional hospitals in a 10-year period in Nigeria. The objective of the study was
      to evaluate the outcome of major amputations in Nigeria. The median age of
      patients was 30 years with male to female ratio 3:1. Ninety of the 100 major
      amputations involved the lower limbs with the above-the-knee/elbow-the-knee ratio
      of 0.5. Trauma was the leading indication for 70 amputations, of these 60 were
      iatrogenic resulting from mismanaged fractures by the traditional bone setters.
      The non-traumatic indications were: diabetic limb gangrene (20); bone
      malignancies (9); and vascular insufficiency (1). Provisional amputation was
      offered in 60 cases, of these 10 had reamputation. There were eight (8.5%)
      mortalities. The functional outcome for this group was discouraging. Only 25
      amputees affording successful prosthetic fitting and social rehabilitation. Major
      amputation in Nigeria foreshadows a dismal existence and emphasizes the need for
      health policies which are effective in controlling the risk factors.

PMID- 10902468
TI  - Postoperative small bowel fistula: back to basics.
AB  - Twenty-one patients presenting between January 1992 and January 1998 with
      postoperative small bowel fistula were reviewed and their management and outcome
      were recorded. There were six jejunal and 15 ileal fistulae. Seven fistulae were
      low output and 14 high output. The management principles included: (i) initial
      resuscitation and skin care; (ii) early surgery for sepsis, or for a high-output
      fistula which showed no signs of decrease by 10 days, or total wound breakdown.
      Surgery involved, where possible, fistula resection with double enterostomy, a
      feeding gastrostomy and abdominal drainage; and (iii) enteral feeding with
      refeeding of enterostomy output into the distal stoma if required to correct
      fluid and electrolyte imbalance and malnutrition. Five patients died and in the
      other 16 their fistulae closed and they are alive and well.

PMID- 10902469
TI  - Laparoscopy in the management of pelvic pain in Calabar, Nigeria.
AB  - During the study period (July 1988 to June 1993), 707 laparoscopies were
      performed in the maternity annex of the University of Calabar Teaching Hospital.
      Fifty-eight (8.2%) were for pelvic pain. Some of the cases of pelvic pain were
      laparoscoped only after failure of other investigative procedures and medical
      treatment. In 45 (77.6%) definitive diagnoses were made and 37 of these became
      asymptomatic after definitive treatment following the laparoscopy. Of the 12
      (20.69%) with no detectable abnormalities, four became asymptomatic with
      explanation and reassurance. All the patients with unruptured and the two with
      ruptured ectopic pregnancy were managed without the need for blood transfusion.
      Most of the diagnostic laparoscopies were performed on a day-case basis. A
      complication rate of 1.7% was recorded. A more liberal use of the procedure in
      the investigation of pelvic pain in women is advocated.

PMID- 10902470
TI  - The prevalence of onchocerciasis and other parasitic infestations on an oil palm
      plantation in Ghana.
AB  - This study was carried out amongst workers of Twifo Oil Palm Plantations (TOPP),
      a large agro-based industry located in the tropical rain forest belt of the
      Central Region of Ghana in West Africa. The district abounds in streams and
      rivers, the biggest being the rapidly flowing River Pra which bisects the
      district. Simulium flies abound in the area and are commonly seen biting
      voraciously especially during the period of the year when farm lands are being
      prepared for cropping. The author assumed the responsibility of providing health
      care for about 1700 employees of the plantation and their dependents in 1988. The
      majority of employees had been engaged without any pre-employment medical
      examination. Available medical information on most workers was inadequate and
      limited to those reporting to the small company clinic. There was no hospital in
      the district and the deplorable roads turned the district into an inaccessible
      island. Meaningful planning for healthcare delivery in the area was difficult.
      This study was conceived as an initial step in identifying the common health
      problems particularly amongst the plantation workers in order to plan necessary
      interventions.

PMID- 10902471
TI  - Anaesthesia in Malawi: complications and deaths.
AB  - The study is a prospective analysis of anaesthesia-associated complications and
      deaths in Malawi. During a period of 6 months 51 complications and 14 deaths in
      3022 anaesthetics were reported. Low blood pressure caused by septicaemia or
      acute blood loss was responsible for 53% of the complications and 71% of deaths.
      Intubating difficulties were responsible for 25% of the complications and 14% of
      the deaths. Eleven of the 14 deaths were identified as avoidable [avoidable
      mortality rate (AMR) 1:275]. Avoidable factors were classified into three groups.
      The anaesthetic AMR was 1:504. Poor fluid management and poor airway management
      were the main avoidable factors. The surgical AMR was 1:3022, and the
      administrative AMR 1:756. Insufficient or no blood is the only factor responsible
      for the administrative AMR. The anaesthetic AMR in Malawi is 6-100 times higher
      than in developed countries such as France, USA or UK. To reduce this very high
      anaesthetic AMR in Malawi further developing aid programmes should concentrate on
      training courses for the anaesthetists and setting up blood donation programmes.

PMID- 10902472
TI  - Successful skin grafting in developing countries.

PMID- 10902473
TI  - A prepaid healthcare scheme in rural Africa.
AB  - Healthcare providers in Africa are having to increasingly rely on the resources
      of the populations they serve. An 8-year experience with one of the first rural
      based health insurance schemes in East Africa is described. Initial difficulties
      included adverse selection of members with chronic ill health, fraudulent claims
      and overuse of health services, leading to considerable financial losses.
      External technical assistance introduced member tracking and regular reports,
      reduced adverse selection, fraud and overuse of services to a minimum, and
      achieved financial stability. Local market research and a comprehensive marketing
      plan is essential for the overall success of an insurance plan. Health insurance
      in this part of Africa is likely to assist middle income earners rather than the
      poor.

PMID- 10902474
TI  - Home-based mother's record: operational feasibility, understanding and usage in a
      rural community in Zimbabwe.
AB  - Utilization of health services is variable but may contribute to the well being
      of women during pregnancy. If people understand when there is a risk of illness
      or death, they are likely to cooperate in reducing those risks and participate in
      their own care. In rural communities people need to be provided with simple but
      scientifically-sound technology adapted to their understanding and needs. One
      such technology is the home-based maternal record (HBMR). We assess the
      feasibility, understanding and usage of a locally adapted HBMR of the World
      Health Organization prototype in a rural community in Binga district, Zimbabwe.

PMID- 10902475
TI  - The pitfalls of measuring changes in smoking habits. Essential NCD Health
      Intervention Project Team.

PMID- 10902476
TI  - Use and abuse of antibiotics: experience at a university teaching hospital in
      Nnewi, Nigeria.

PMID- 10902477
TI  - Body weight and drug dose in medical patients in Cambodia.

PMID- 10902478
TI  - Neonatal resuscitation: a report from Oman.
AB  - There has been a considerable increase in the educational level and awareness of
      neonatal care in developing countries over last decade. The importance of
      neonatal resuscitation, however, has been ignored. This report discusses the
      importance of structured neonatal courses with emphasis on the need for more such
      courses at regional levels, especially in developing countries. The concept of
      basic and advanced life support of the newborn is also presented.

PMID- 10902479
TI  - Sclerotherapy for large hydrocoeles in Nigeria.
AB  - Sclerotherapy with tetracycline hydrochloride was used to treat 99 patients with
      large hydrocoeles (range 300-1500 ml). The mean age of these patients was 52
      years. In 55.5% of the patients one treatment was adequate. Two treatments were
      required in 22%; three in 10%; four in 3%; and five in 7% of the patients. In two
      patients sclerotherapy failed. Complications were minimal. Only 15% of the
      patients complained of severe pain. The overall success rate was 98%.
      Tetracycline sclerotherapy for large hydrocoeles is effective, safe and
      economical and is preferred for older patients who are at risk from anaesthetic
      complications.

PMID- 10902481
TI  - Diarrhoeal disease.

PMID- 10902480
TI  - Post-spinal headache after dural puncture with perpendicular or horizontal needle
      bevel direction: a randomized controlled trial in an African rural hospital.

PMID- 10902482
TI  - Methods of fluid administration for resuscitation and hydration under difficult
      circumstances: Part 2--alternative routes.

PMID- 10902483
TI  - The health worker and HIV in high-incidence poor countries: Part 1--HIV and the
      health worker.

PMID- 10902484
TI  - The Global Lymphatic Filariasis Initiative.

PMID- 10902485
TI  - Abdominal pregnancy in Zimbabwe: guidelines in management in rural districts of
      developing countries.

PMID- 10902486
TI  - Sinus histiocytosis and massive lymphadenopathy in two Ghanaian brothers.

PMID- 10902487
TI  - Renal tuberculosis in children.

PMID- 10902488
TI  - Roadside vulcanizing and welding can cause blast injuries.

PMID- 10902489
TI  - Analysis of surgical admissions to Debre Markos Hospital.

PMID- 10902490
TI  - Fracture management in Anjouan: comparison of operative and non-operative
      treatment methods.

PMID- 10902491
TI  - Branded--tattooing in prisons.

PMID- 10902492
TI  - Cases of kala-azar without any hepatosplenomegaly.

PMID- 10902493
TI  - Myocardial injury: an unrecognized complication of cerebral malaria.

PMID- 10902494
TI  - Community informed consent for HIV testing.

PMID- 10902496
TI  - Safety of injections--facts and figures.

PMID- 10902495
TI  - Buerger's disease in Nepal.

PMID- 10902497
TI  - Debt relief policies could be fuelling African AIDS epidemic, warns new report.

PMID- 10902498
TI  - Progress towards poliomyelitis eradication, South-East Asia, 1998-1999.

PMID- 10902499
TI  - Accidental exposure to smallpox vaccine, Russian Federation.

PMID- 10902501
TI  - Lymphatic filariasis.

PMID- 10902500
TI  - Protection-at-birth (PAB) method, Tunisia.

PMID- 10902502
TI  - [Is the interest in studies of the questions of medical training increasing in
      Germany?].

PMID- 10902503
TI  - [Innovative course concept for small group teaching in clinical methods. Results
      of a longitudinal, 2-cohort study in the setting of the medical didactic pilot
      project in Dusseldorf].
AB  - BACKGROUND AND OBJECTIVE: Medical students in Germany often criticize the
      anonymous and not practice-orientated way they are taught. It was the aim of this
      study to develop, try out and evaluate cost-effectiveness of practice-oriented
      interdisciplinary teaching in small groups. PATIENTS AND METHODS: The study was
      based on ca. 300 medical students/year, a practicable number in relation the
      average annual total intake by German medical schools. Between 1995 and 1998, 300
      medical students annually, chosen by lot, were offered voluntary additional
      teaching of imaging methods (computed tomography, endoscopy and sonography), from
      a total of 2485 students (1276 females, 1209 males; mean age 25.8 years), the
      reminder serving as controls. After lecture-demonstration to all, the selected
      small groups were separately taught. They performed sonography on each other in
      small cohorts of 5 or they practised endoscopies on phantom models under
      supervision of a student tutor. In addition, lecturers circulated among the
      groups to answer additional questions and provide further help. All participants
      evaluated the course concept and the instructors on a questionnaire provided by
      the interdisciplinary centre for tertiary education. The effects of teaching on
      the participants were tested by a practical test in the form of an objective
      structured clinical examination (OSCE). RESULTS: Ca. 80% of course participants
      reached the intended aim and passed the OSCE examination. They gave the
      instructions in the pilot project highest marks, in all its criteria nearly one
      mark higher than those of other evaluated teaching sessions. Pre-clinical
      students judged the programme even more favourably than those in their clinical
      years. The additional cost incurred was moderately low at ca. DM 67 per year per
      student. CONCLUSION: Modern practice-oriented small group teaching will provide
      high quality results even with large numbers of students. The concept has already
      been taken over by other medical faculties.

PMID- 10902504
TI  - [An interuniversity comparison of the supervision of doctoral candidates--should
      the promotion procedures be changed?].
AB  - BACKGROUND AND OBJECTIVE: There are only few investigations on supervision of
      medical dissertations that allow a comparison between different universities.
      This article discusses how the medical dissertation can be incorporated into a
      new medical curriculum. METHODS: A questionnaire was sent to all medical students
      in Lubeck who wrote dissertations in 1998. It contained 28 questions on duration,
      supervision, impact on medical studies and possible changes in the dissertation
      process. The data were compared statistically to previous studies. RESULTS: 70
      questionnaires could be evaluated (63%) which allowed a comparison with studies
      in Hannover and Erlangen-Nurnberg. The Lubeck students assessed their supervision
      to be significantly better, they worked more frequently on experimental topics
      and data of their research were published more often than was the case in the
      other two institutions. The students regularly needed one extra semester for
      their dissertation, especially those working on experimental topics. Those who
      wrote dissertations expressed criticism of the dissertation process: only one
      third were in favour of making no change in the process. When asked to suggest
      possible improvements they proposed having a central facility for the
      announcement of dissertation subjects and one free semester to work solely on the
      dissertation. CONCLUSION: In order to evaluate and compare supervision of
      dissertations, a comparable questionnaire should be used by all medical
      universities. If the medical curriculum is changed, the dissertation either has
      to be firmly integrated in the curriculum or it should be undertaken after
      completion of the studies.

PMID- 10902505
TI  - [Twelve-year experience with the "Doctor in Practice"].

PMID- 10902506
TI  - [How would I become am internist? Advanced training and professional chance in
      Switzerland].

PMID- 10902508
TI  - [What knowledge and skills must the future internist have in 2010?].

PMID- 10902507
TI  - [Situation for advanced training in internal medicine in Germany].

PMID- 10902509
TI  - [Angiomyolipoma of the liver].
AB  - HISTORY AND ADMISSION FINDINGS: A 66-year-old woman, known for 4 years to have a
      space-occupying lesion in the liver thought to be a lipoma, was admitted because
      the increasing size of the mass. She was hypertensive and had recurrent
      supraventricular tachycardia, but was otherwise asymptomatic and physical
      examination was unremarkable. INVESTIGATIONS: Laboratory tests were within normal
      limits. Abdominal ultrasound demonstrated a well-circumscribed, echodense space
      occupying lesion. Magnetic resonance imaging revealed a hyperintense encapsulated
      tumour with contrast-medium enhancement. DIAGNOSIS AND TREATMENT: Because the
      imaging tests were equivocal, a segmental liver resection was performed to
      exclude malignancy. Histological examination revealed an angiomyolipoma of the
      liver. CONCLUSION: Angiolipoma is a benign mixed-cell tumour that very rarely
      affects the liver but must be included in the differential diagnosis of hepatic
      space-occupying lesions. Its manifestations may be highly variable and
      histological examination is required if there is any uncertainty about possible
      malignancy. If the biopsy is diagnostic of a benign lesion, expectant observation
      with regular monitoring is indicated.

PMID- 10902511
TI  - [Ultrasound of the gastrointestinal tract: good educational background is
      required].

PMID- 10902510
TI  - [Clinical significance of leptin].

PMID- 10902512
TI  - [Ultrasound diagnosis of pseudomembranous colitis].
AB  - BACKGROUND AND OBJECTIVE: The diagnosis of pseudomembranous colitis (PMC) is
      based on the history of exposure to antibiotics, characteristic endoscopic
      findings and on demonstrating the presence of Clostridium difficile toxins in the
      faeces. This report presents typical sonographic features of PMC. PATIENTS AND
      METHODS: The sonograms of 13 patients with PMC (7 males, 6 females, median age 70
      years, range 55-84 years), were retrospectively analyzed. Patients' histories,
      clinical findings, the results of colonoscopy including histological findings and
      microbiological tests were related to the sonographic features of inflammation of
      the colon. RESULTS: At sonography the wall of the colon was thickened (6-17 mm)
      in each of the patients, different types of changed wall-architecture were seen.
      In 85% sonographic signs of colitis were restricted to the left colon, whereas in
      15% a pancolitis was diagnosed. Ascites was detected in 38%, the colon contents
      were visible in 85%, in 77% the lumen was narrowed. Colonoscopy confirmed the
      diagnosis in six patients, in two patients endoscopy was performed only to
      control the effect of therapy and in five patients endoscopy was thought to be
      unnecessary. CONCLUSION: Sonography can supplement history and clinical findings
      if PMC is suspected. Potentially life-saving therapy can be initiated even if
      colonoscopy has not been performed and results of microbiological assessment are
      not yet available. However, the diagnosis of PMC remains to be based on the gold
      standard of colonoscopy and histological findings.

PMID- 10902513
TI  - [Ultrasound diagnosis of penicillin-induced segmental hemorrhagic colitis].
AB  - INTRODUCTION: Penicillin-induced segmental haemorrhagic colitis (SHC) is a
      characteristic and striking but rarely diagnosed clinical entity. Bloody diarrhea
      and abdominal cramps start a few days after the intake of oral penicillin
      derivatives. We report the ultrasonographic and clinical findings in nine
      patients with SHC and compare the results with the findings in ten patients with
      antibiotic-related pseudomembranous colitis (PMC). METHODS: Nine consecutive
      patients with SHC (age: 32 +/- 10 years; five males, four females) with PMC
      negative proctoscopic findings, stool cultures and negative clostridium difficile
      toxin and ten patients with PMC (age: 50 +/- 18 years; six males, four females)
      with positive proctoscopy and Clostridium difficile toxin were clinically
      evaluated and examined by high resolution ultrasonography. The sonographic
      findings of the colonic and small bowel walls as well as the clinical course of
      the diseases were documented. RESULTS: In all nine patients with SHC the wall of
      the ascending colon was asymmetrically thickened with loss of layer structure.
      Neither the small bowel nor the cecum were involved in patients with SHC. In all
      cases a distinct border between involved and uninvolved colon wall was found.
      During follow-up all patients recovered soon after stopping antibiotic treatment
      and symptomatic care. In seven of ten patients with PMC pancolitis and in three
      of ten with left-sided colitis were found at ultrasonography. In all patients
      with PMC the bowel wall was symmetrically thickened with the layers remaining
      distinct. DISCUSSION: The knowledge of the clinical characteristics and
      sonographic findings of penicillin-induced segmental haemorrhagic colitis may
      reduce the need for invasive endoscopic and radiological investigations in
      diagnosis and follow-up. The age of patients, clinical course and sonographic
      findings may be helpful in differentiating patients with SHC and PMC.

PMID- 10902514
TI  - [Severe vitamin D deficiency osteomalacia by coincidence of multiple risk
      factors].
AB  - HISTORY: An 82-year-old woman was admitted with bilateral clavicular fractures
      after falling out of bed. She complained of pain in all her bones. She reported
      having undergone a partial gastrectomy (Billroth II) 40 years ago with subsequent
      milk intolerance and a dislike of direct sun light. INVESTIGATIONS: Scintigraphy
      revealed multiple areas of abnormal uptake. Conventional radiography showed in
      both ulnae transverse zones of increased density with a central translucent band.
      Laboratory tests demonstrated the constellation of increased bone turnover in
      secondary hyperparathyroidism with hypocalcaemia (1.49 mmol/l) and
      hypophyosphataemia (0.62 mmol/l). The 25-hydroxyvitamin D-level was too low to be
      measured. Ileal crest biopsy indicated osteomalacia. TREATMENT AND COURSE: Serum
      levels of calcium, alkaline phosphatase and vitamin D became normal after 7 weeks
      of daily administration of 10,000 IU vitamin D and 1000 mg calcium. The severe
      pains had subsided after two weeks and no longer required analgesics. CONCLUSION:
      Multiple areas of increased uptake on skeletal scintigraphy, combined with
      diffuse bone pain and increased alkaline phosphatase, were at first
      misinterpreted as extensive skeletal metastases. But the history, at first
      seemingly of little significance, contained three long-term risk factors for the
      development of vitamin D and calcium deficiency and thus of osteomalacia, namely
      partial gastrectomy, milk intolerance and inadequate exposure to sun light. Early
      recognition of risk factors for bone changes will rapidly lead to the correct
      diagnosis and immediate treatment of the treatable underlying disease.

PMID- 10902515
TI  - [High PCP blood level caused by PCP contaminated leather clothing].

PMID- 10902516
TI  - [Malignant pheochromocytoma combined with multiple renal cell carcinomas and a
      renal cyst. Indication for von Hippel-Lindau syndrome?].

PMID- 10902517
TI  - [Metabolic complications of antiretroviral therapy of HIV infection].

PMID- 10902518
TI  - [Advantages of intraoperative neuromonitoring in thyroid gland operations].

PMID- 10902519
TI  - [Neuromonitoring of the recurrent laryngeal nerve: of value for the supplier].

PMID- 10902520
TI  - [Surgery of the failing left ventricle].

PMID- 10902521
TI  - [From the cell to molecular structure--changes in pathogenetic thinking].

PMID- 10902522
TI  - "Virtual" experiment for understanding the electrocardiogram and the mean
      electrical axis.
AB  - Educators have placed an emphasis on the development of laboratory materials that
      supplement the traditional lecture format. The laboratory materials should
      encourage active learning, small group discussion, and problem-solving skills. To
      this end, we developed a virtual experiment designed to introduce students to the
      theory and application of the electrocardiogram (ECG) and the mean electrical
      axis (MEA). After reviewing background material, the students will analyze ECG
      recordings from two individuals who underwent a series of experimental
      procedures. The students are challenged to reduce and analyze the data, calculate
      and plot the MEA, and answer questions related to the theory and application of
      the ECG. In conducting the virtual experiment, students are introduced to inquiry
      based learning through experimentation.

PMID- 10902523
TI  - Use of brook char (Salvelinus fontinalis) physiological responses to stress as a
      teaching exercise.
AB  - Fish hematological changes during osmotic and cold stress are used to introduce
      the physiological reactions of the animal to an acute stress. Brook char
      (Salvelinus fontinalis) were subjected to 1 h of stress before being anesthetized
      and having blood taken from their caudal vein. Glucose, hemoglobin, hematocrit,
      and osmolarity were determined in the blood samples. Analyses showed that glucose
      concentration tends to increase and hematocrit tends to decrease in stressed
      fish. Changes in hemoglobin concentration occurred only in cold-stressed fish. A
      rise in blood glucose concentration is the result of cortisol secreted by the
      hypothalamic-pituitary-adrenal axis. The glucose produced is used as an osmolyte
      or energy source to resist or combat the stress. In stressed fish, changes in
      hematocrit could be the result of the osmoconcentration of the blood plasma, as
      shown by the increase in osmolarity for the same group. In cold-stressed fish, a
      decrease in hemoglobin concentration could be the result of hemodilution by body
      cell water.

PMID- 10902524
TI  - Renal response to volume expansion: learning the experimental approach in the
      context of integrative physiology.
AB  - We describe a laboratory experience for upper-level science students that
      provides a hands-on approach to understanding the basics of experimental
      physiology. A pre-lab, interactive tutorial develops the rationale for this
      experiment by reviewing the renal and cardiovascular mechanisms involved in the
      response to extracellular fluid volume expansion. After a hypothesis is stated,
      an experiment is designed to determine the relative importance of dilution of
      plasma proteins to the overall renal excretory response following volume
      expansion with intravenous saline. In the lab, students collect data from two
      groups of anesthetized rats. The protocol involves continuous monitoring of
      arterial pressure and periodic collection of urine and blood samples after volume
      expansion with either isotonic NaCl or isotonic NaCl plus 5% albumin. A post-lab
      tutorial is used to analyze, interpret, and discuss the data. Students next
      prepare an oral presentation, practice it, and finally present their results and
      answer questions before peers and instructors. This overall experience involves
      all of the components of doing a "real" experiment, starting with a question that
      is not answered in general textbooks of physiology and finishing with an oral
      presentation of the results. Along the way, students gain a better understanding
      of a complex homeostatic response and learn the care and value of using animals
      in research and teaching.

PMID- 10902526
TI  - Exploring the context of biomedical research through a problem-based course for
      undergraduate students.
AB  - Students in an interdisciplinary program explored the manufacture of biomedical
      knowledge in a problem-based course. Because the class size was two to three
      times larger than the normal tutorial group, suitable modifications were made
      (formation of floating groups around defined learning tasks, formal
      presentations, written reports, and evaluations by students and tutor). A variety
      of problems and/or cases drawn from research papers, newspapers, biographies, or
      web pages permitted students to appreciate the complex interactions between
      ideals, individuals, institutions, and investments that comprise modern
      biomedical research.

PMID- 10902525
TI  - Modeling of blood flow as the result of filtration-reabsorption processes in
      capillaries.
AB  - In our previous article (Am J Physiol Adv Physiol Educ 272: S26-S30, 1997) we
      proposed a model that permits analysis for the change of hemodynamics in vessels
      with local stenosis. This problem is connected with the blood-tissue metabolism.
      This article continues the classroom research on concepts related to blood flow
      physiology. We take into consideration the problem of the blood-tissue fluid
      exchange. A model based on basic principles of hydrodynamics and mathematics is
      proposed for analysis of "filtration-reabsorption equilibrium" and its
      disturbances under different external influences. It permits medical students to
      develop a scientific analytic approach to the solution of physiological and
      pathophysiological hemodynamics problems.

PMID- 10902527
TI  - Manuscript peer review: a helpful checklist for students and novice referees.
AB  - The ability to contribute consistent, fundamentally sound critiques is an
      essential element of the scientific peer review process and an important
      professional skill for investigators. Despite its importance, many students and
      junior scientists do not have an adequate working knowledge of how to effectively
      critique research manuscripts. Part of the problem, in our view, is that novice
      referees often lack a comprehensive understanding of the basic issues that should
      be considered in evaluating scientific articles. Specifically, they tend to
      overemphasize certain limitations (usually methodological), while missing other
      key points related to the scientific method that should be weighed much more
      heavily. In our journal club and graduate courses we have been using a
      "checklist" to help graduate students and postdoctoral fellows critically analyze
      original research papers. In this article we present these guidelines in the hope
      that they will serve as a helpful resource for students and other novice
      reviewers when critiquing scientific manuscripts.

PMID- 10902528
TI  - Student test scores are improved in a virtual learning environment.
AB  - This study evaluates the effectiveness of delivering the core curriculum of an
      introductory neuroscience course using a software application referred to as a
      virtual learning interface (VLI). The performance of students in a virtual
      learning environment (VLE) is compared with that of students in a conventional
      lecture hall in which the same lecturer presented the same material. This study
      was not designed to determine whether grades are improved by augmenting a lecture
      with other information. The VLI takes advantage of audio, video, animation, and
      text in a multimedia computer environment. Our results indicate that raw average
      scores on weekly examinations were 14 percentage points higher for students in
      the VLE compared with those for students in a conventional lecture hall setting.
      Moreover, normalized test scores were over 5 points higher for students in the
      VLE. This analysis suggest that a core curriculum can be effectively presented to
      students using the VLE, thereby making it possible for faculty to spend less
      class time relaying facts and more time engaging students in discussion of
      scientific theory.

PMID- 10902529
TI  - Mailing lists are preferred to newsgroups as teaching tools for undergraduate
      biology classes.
AB  - Effective communication between instructors and students is a challenge
      regardless of the instructor-to-student ratio. Instructors of large classes, in
      particular, have resorted to various forms of Internet communication, such as
      mailing lists and newsgroups, to supplement class time and office hours. Mailing
      lists are closed discussions among subscribers who receive and send messages via
      an electronic mail program (e.g., Eudora). Newsgroups are public discussions to
      which anyone can gain access and respond via a newsreader program (e.g.,
      Nuntius). Newsgroup messages are posted to a bulletin board that the subscriber
      must visit to read. Mailing lists and newsgroups share many advantages
      (convenience, greater anonymity, and speed of communication) and disadvantages
      (computer access required, impersonal nature, junk mail, and lack of graphics in
      older programs). However, surveys of both faculty and students in biology
      indicate that mailing lists are generally favored over newsgroups. Reasons given
      for mailing list popularity included greater familiarity with the E-mail format
      and ease of access.

PMID- 10902530
TI  - Quantitative concept mapping in pulmonary physiology: comparison of student and
      faculty knowledge structures.
AB  - Quantitative concept mapping, in contrast with qualitative approaches, is
      rigorous scientifically and permits statistical analyses of data about concept
      learning. This study extends past quantitative research on the structure of
      student concept learning in pulmonary physiology. Pathfinder scaling is used to
      derive concept maps for medical and veterinary students and their physiology
      instructors at Northwestern University and the University of Wisconsin,
      respectively. The concept maps are evaluated for coherence (internal
      consistency), student-instructor similarity, and correlation of similarity with
      final examination scores. Results show that student and instructor concept maps
      are coherent and that student concept maps become increasingly similar to
      instructors' concept maps from pre- to postinstruction, but that student
      instructor concept map similarity does not correlate with examination
      performance. Research outcomes are discussed concerning possible sources of
      variation in student and faculty knowledge structures.

PMID- 10902531
TI  - Helping undergraduates repair faulty mental models in the student laboratory.
AB  - Over half of the undergraduate students entering physiology hold a misconception
      concerning how breathing pattern changes when minute ventilation increases.
      Repair of this misconception was used as a measure to compare the impact of three
      student laboratory protocols on learning by 696 undergraduate students at 5
      institutions. Students were tested for the presence of the misconception before
      and after performing a laboratory activity in which they measured the effect of
      exercise on tidal volume and breathing frequency. The first protocol followed a
      traditional written "observe and record" ("cookbook") format. In the second
      treatment group, a written protocol asked students to complete a prediction table
      before running the experiment ("predictor" protocol). Students in the third
      treatment group were given the written "predictor" protocol but were also
      required to verbalize their predictions before running the experiment
      ("instructor intervention" protocol). In each of the three groups, the number of
      students whose performance improved on the posttest was greater than the number
      of students who performed less well on the posttest (P < 0.001). Thus the
      laboratory protocols helped students correct the misconception. However, the
      remediation rate for students in the "instructor intervention" group was more
      than twice that observed for the other treatment groups (P < 0.001). The results
      indicate that laboratory instruction is more effective when students verbalize
      predictions from their mental models than when they only "discover" the outcome
      of the experiment.

PMID- 10902532
TI  - Comparison of naive and experienced students of elementary physiology on
      performance in an advanced course.
AB  - The purpose of this study was to determine whether, in comparison with naive
      students, experienced students who have completed an elementary physiology course
      1) have a greater knowledge level of physiology and 2) perform better in an upper
      division physiology course. The educational setting for this study was the
      cardiovascular block of an advanced undergraduate level course entitled
      Principles of Human Physiology (PGY 412). The study employed students who had
      completed elementary physiology (PGY 206) at the University of Kentucky (group
      1), students who had completed elementary physiology in another academic program
      (group 2), and naive students with no prior physiology experience (group 3). A
      cardiovascular pretest was presented during the opening session of the
      cardiovascular block in PGY 412. Respective scores for the three groups were
      29.4%, 31.7%, and 24.1%, and there were no significant between-group differences.
      Respective scores on the same pretest items given as a posttest at the end of the
      cardiovascular block were 90.4%, 91.4%, and 90.4%, and, again, there were no
      significant between-group differences. Respective scores on other cardiovascular
      test items given at the end of the block were 78.9%, 78.7%, and 81.1%.
      Interestingly, the highest score here was achieved by the naive students (group
      3), but, once again, between-group differences were not significant. In summary,
      on the basis of pretest/posttest examination of cardiovascular physiology between
      naive and experienced students, the results of this study indicate 1) that the
      common assumption that students entering advanced level physiology courses have a
      significant retention of knowledge from elementary physiology is not valid and 2)
      that completion of an elementary physiology course does not offer an advantage in
      learning advanced material.

PMID- 10902533
TI  - Information age testing: making rigorous exams fun to write and easy to grade.
AB  - This essay discusses methods by which an exam writer can achieve three
      objectives: 1) producing questions that test a student's understanding, defined
      as the ability to apply knowledge in a novel context; 2) writing questions that
      require minimal grading time; and 3) keeping current and excited about the field,
      which is critical for transmitting personal enthusiasm to students. Included are
      descriptions of practical, time-saving methods for processing and filing
      examination material; ways to use readily available databases for quickly
      generating rigorous, interesting questions, with examples of questions generated
      in this way; suggestions for structuring questions so that they are easily
      graded; and general advice for preparing students to take this kind of
      examination.

PMID- 10902534
TI  - How to help students understand physiology? Emphasize general models.
AB  - Students generally approach topics in physiology as a series of unrelated
      phenomena that share few underlying principles. In many students' view, the Fick
      equation for cardiac output is fundamentally different from a renal clearance
      equation. If, however, students recognize that these apparently different
      situations can be viewed as examples of the same general conceptual model (e.g.,
      conservation of mass), they may gain a more unified understanding of
      physiological systems. An understanding of as few as seven general models can
      provide students with an initial conceptual framework for analyzing most
      physiological systems. The general models deal with control systems, conservation
      of mass, mass and heat flow, elastic properties of tissues, transport across
      membranes, cell-to-cell communication, and molecular interaction.

PMID- 10902535
TI  - In vivo research with stable isotopes in biochemistry, nutrition and clinical
      medicine: an overview.
AB  - Tracers and kinetic modelling provide the opportunity to follow the movement and
      to quantify the metabolic fates of biological compounds in vivo. For studies in
      children and for repeated studies in adults, the use of stable isotopically
      labelled substrates are preferable and safe. Measurement of isotopic enrichment
      in biological molecules is highly specific and can be extremely precise. This
      allows the development of models of biological system dynamics in cells and
      organs that are otherwise inaccessible for sampling. Applications in
      biochemistry, nutrition and clinical medicine show the potential of stable
      isotopes in vivo. Methodology is of paramount importance and includes the choice
      of bolus studies, (primed) continuous infusions, use of multiple tracers and use
      of isotopomer information and intrinsic labels. There is no limit to the number
      and kind of compounds that can be traced. Topics include intermediate metabolism
      (lipids, proteins and carbohydrates) using hydrogen, carbon and nitrogen labels.
      In clinical medicine, 13C-breath tests are available for detection of
      Helicobacter pylori ([13C]urea breath test), and for assessment of a variety of
      gastro-intestinal and hepatic functions (e.g. [13C]octanoate and mixed
      [13C]triglyceride breath tests for studies of gastric emptying and fat
      absorption, respectively). Because theoretical, methodological, physiological and
      practical aspects are intertwined, in vivo research with stable isotopes demands
      close collaboration between the clinical researcher and the chemist responsible
      for the mass spectrometry.

PMID- 10902536
TI  - Intestinal absorption of calcium from foodstuffs as compared to a pharmaceutical
      preparation.
AB  - Only few data are available on intestinal calcium absorption from foodstuffs and
      composite meals in humans. The aim of the study was to compare intraindividually
      the calcium absorption from milk and from a breakfast with that from a
      pharmaceutical calcium preparation of equal calcium content. In 8 healthy
      volunteers between 44 and 58 years of age, the intestinal calcium absorption was
      measured in randomized order applying the double isotope technique from: (1)
      500ml of fresh milk (equivalent to 620mg Ca), (2) a test meal composed of 250 g
      curd, 150g yoghurt, 3 slices pineapple, 2 breakfast rolls, 2 cups of coffee, 10g
      of coffee cream, 20g butter, 50g jam and 20g honey (equivalent to 580mg Ca), and
      (3) a lactogluconate effervescent tablet (equivalent to 500mgCa). All test doses
      were given on an empty stomach and labelled with 20mg 44Ca. Simultaneously, 5mg
      42Ca in a sterile isotonic solution were injected intravenously. The mean values
      of the absorbed fractions are 24.0% +/- 5.4% (mean +/-SD), 17.9% +/- 7.1%, and
      28.7% +/- 9.1% for the milk, for the meal and for the tablet respectively. The
      data show that less calcium is absorbed from foodstuffs as compared to a
      preparation of optimal bioavailability. But in this study only the difference
      between absorption from the milk and from the meal was statistically significant.
      Therefore, it is possible to obtain a sufficient calcium supply of the human body
      also by properly selected foodstuffs.

PMID- 10902537
TI  - Secretion of 13C-labelled oligosaccharides into human milk and infant's urine
      after an oral [13C]galactose load.
AB  - Human milk oligosaccharides seem to play an important role in the infant's
      defense against bacterial and viral infections of the gastrointestinal and the
      urogenital tract. In this study, we investigated the influence of dietary
      carbohydrates on the biosynthesis of lactose and oligosaccharides in the human
      mammary gland and their renal excretion by the human milk-fed infant. For this
      purpose, a lactating woman was given 27 g galactose (Gal) containing 2 g [13C]
      Gal (1-13C/99%) immediately after breakfast. In the following 36 h, milk (5-10
      ml) was collected before each nursing. Infant's urine was collected over a period
      of 24 h. 13C-enrichment was measured in total milk, milk fat and protein, in the
      carbohydrate fraction as well as in urine by isotope ratio mass spectrometry
      (IRMS). Milk carbohydrates and deproteinized urine samples were fractionated by
      Sephadex G25 gel filtration and further analyzed by IRMS, high performance thin
      layer chromatography and and high pH anion exchange chromatography with pulsed
      amperometric detection (HPAEC-PAD). IRMS revealed that in milk a maximal delta
      13CPDB was reached within 8 h after Gal intake which then rapidly declined in the
      following 8 h. The cumulative 13C-elimination over this first peak was 6.9% of
      the oral 13C-dose. The highest 13C-enrichment was detectable in the carbohydrate
      fraction, mainly in lactose and neutral oligosaccharides. Compared to the
      enrichment of human milk, the delta 13CPDB of infant's urine was delayed. In
      urine, the highest amount of 13C was found in the Sephadex G25 fractions which
      mainly contained lactose, fucosyl-lactose, lacto-N-tetraose (LNT), fucosyl-LNT
      and difucosyl-LNT. For further characterization, individual components were
      separated by HPAEC-PAD and subsequently analyzed by fast atom bombardment mass
      spectrometry and IRMS. The data show, that orally applied Gal is incorporated in
      milk, especially in lactose and neutral oligosaccharides. Obviously, some of
      these components were absorbed by the infant and then excreted with urine. There,
      oligosaccharides may serve as analogous receptors for bacterial or viral adhesion
      molecules, and, hence, may prevent urogenital infections in breastfed infants.

PMID- 10902538
TI  - Application of deuterated compounds for investigations of percutaneous absorption
      of chemical substances.
AB  - The percutaneous absorption of the xenoestrogen 2,2-bis-(4-hydroxyphenyl)-propane
      (bisphenol A) 1 has been studied and compared with results on dibenzoyl peroxide
      2, a component of drug formulations for topical application. Isolated perfused
      bovine udders from slaughtered cows were employed as models for human skin. The
      deuterium labelled compounds 1-d14 and 2-d10 were applied to enhance the
      reliability of GC-MS trace determinations by use of reverse isotope dilution
      analysis. 1-d14 was found in perfusate and milk equivalent samples obtained
      between 60 and 300 min after topical application with maximum concentrations
      between 120 and 180 min. 1-d14 was enriched in the milk samples by a factor of
      about 300 compared with the perfusate. The results confirm a possible penetration
      of 1 from the environment through the skin into the capillary system. 2 studied
      on the same model system penetrated faster than 1 by a factor of about three.

PMID- 10902539
TI  - Mitochondrial DNA recombination-no need to panic.
AB  - Recombination has recently been invoked as an explanation for the large amount of
      homoplasy observed in a collection of complete or nearly complete human
      mitochondrial sequences. Here we show that some of the data on which this
      conclusion was based are likely to be unreliable and that if these data are
      excluded, the results are no longer significant.

PMID- 10902541
TI  - Eukaryotic non-coding DNA is functional: evidence from the differential scaling
      of cryptomonad genomes.
AB  - Genic DNA functions are commonplace: coding for proteins and specifying non
      messenger RNA structure. Yet most DNA in the biosphere is non-genic, existing in
      nuclei as non-coding or secondary DNA. Why so much secondary DNA exists and why
      its amount per genome varies over orders of magnitude (correlating positively
      with cell volume) are central biological problems. A novel perspective on
      secondary DNA function comes from natural eukaryote eukaryote chimaeras
      (cryptomonads and chlorarachneans) where two phylogenetically distinct nuclei
      have coevolved within one cell for hundreds of millions of years. By comparing
      cryptomonad species differing 13-fold in cell volume, we show that nuclear and
      nucleomorph genome sizes obey fundamentally different scaling laws. Following a
      more than 125-fold reduction in DNA content, nucleomorph genomes exhibit little
      variation in size. Furthermore, the present lack of significant amounts of
      nucleomorph secondary DNA confirms that selection can readily eliminate
      functionless nuclear DNA, refuting 'selfish' and 'junk' theories of secondary
      DNA. Cryptomonad nuclear DNA content varied 12-fold: as in other eukaryotes,
      larger cells have extra DNA, which is almost certainly secondary DNA positively
      selected for a volume-related function. The skeletal DNA theory explains why
      nuclear genome size increases with cell volume and, using new evidence on
      nucleomorph gene functions, why nucleomorph genomes do not.

PMID- 10902540
TI  - Analysis of the complete mitochondrial DNA sequence of the brachiopod
      terebratulina retusa places Brachiopoda within the protostomes.
AB  - Brachiopod phylogeny is still a controversial subject. Analyses using nuclear
      18SrRNA and mitochondrial 12SrDNA sequences place them within the protostomes but
      some recent interpretations of morphological data support a relationship with
      deuterostomes. In order to investigate brachiopod affinities within the metazoa
      further, we compared the gene arrangement on the brachiopod mitochondrial genome
      with several metazoan taxa. The complete (15 451 bp) mitochondrial DNA (mtDNA)
      sequence of the articulate brachiopod Terebratulina retusa was determined from
      two overlapping long polymerase chain reaction products. All the genes are
      encoded on the same strand and gene order comparisons showed that.only one major
      rearrangement is required to interconvert the T. retusa and Katharina tunicata
      (Mollusca: Polvplacophora) mitochondrial genomes. The partial mtDNA sequence of
      the prosobranch mollusc Littorina saxatilis shows complete congruence with the T.
      rehtusa gene arrangement with regard to the ribosomal and protein coding genes.
      This high similarity in gene arrangement is the first to be reported within the
      protostomes. Sequence analyses of mitochondrial protein coding genes also support
      a close relationship of the brachiopod with molluscs and annelids, thus
      supporting the clade Lophotrochozoa. Though being highly informative, sequence
      analyses of the mitochondrial protein coding genes failed to resolve the
      branching order within the lophotrochozoa.

PMID- 10902542
TI  - The variance in inbreeding depression and the recovery of fitness in bottlenecked
      populations.
AB  - Theoretical analyses of inbreeding suggest that following an increased degree of
      inbreeding there may be a temporary recovery of fitness, because of selection
      either within or among inbred lineages. This is possible because selection can
      act more efficiently to remove deleterious alleles given the greater homozygosity
      of such populations. If common, recovery of fitness following inbreeding may be
      important for understanding some evolutionary processes and for management
      strategies of remnant populations, yet empirical evidence for such recovery in
      animals is scant. Here we describe the effects of single-pair population
      bottlenecks on a measure of fitness in Drosophila melanogaster. We compared a
      large number of families from each of 52 inbred lines with many families from the
      outbred population from which the inbred lineages were derived. Measures were
      made at the third and the 20th generations after the bottleneck. In both
      generations there was, on average, substantial inbreeding depression together
      with a highly significant variance among the inbred lines in the amount of
      fitness reduction. The average fitness of inbred lines was correlated across
      generations. Our data provide evidence for the possibility of recovery of fitness
      at two levels, because (i) the average fitness reduction in the F20 generation
      was significantly less than in the F3 generation, which implies that selection
      within lines has occurred, and (ii) the large variance in inbreeding depression
      among inbred lines implies that selection among them is possible. The high
      variance in inbreeding depression among replicate lines implies that modes of
      evolution which require a low level of inbreeding depression can function at
      least in a fraction of inbred populations within a species and that results from
      studies with low levels of replication should be treated with caution.

PMID- 10902543
TI  - Global dispersal reduces local diversity.
AB  - Metapopulation models and stepping-stone models in genetics are based on very
      different underlying dispersal structures, yet it can be difficult to distinguish
      the behaviour of the two kinds of models. We demonstrate a striking qualitative
      difference in the equilibrium behaviour possible with these two kinds of
      dispersal. If, in a local patch, there are multiple stable equilibria (and
      consequently an unstable equilibrium), we demonstrate that, for the spatial
      system with a metapopulation structure, at equilibrium every patch has to be near
      one of the stable equilibria. This contrasts with the clinal structure possible
      with a stepping-stone or continuous space model; thus the result can be used to
      deduce qualitative information about the form of dispersal from observations of
      allele frequencies.

PMID- 10902544
TI  - High variation in multiple paternity of domestic cats (Felis catus L.) in
      relation to environmental conditions.
AB  - Paternity was analysed in two domestic cat (Felis catus) populations differing in
      habitat structure (rural versus urban) and density (234 cats km-2 versus 2,091
      cats km-2). A total of 312 offspring, 76 mothers and 65 putative fathers were
      typed at nine microsatellite loci in the two populations. Our data showed a high
      rate of multiple paternity in the urban population (70-83% of litters with more
      than one father), whereas it was much lower in the rural population (0-22% of
      litters with more than one), as most males were able to monopolize the entire
      litter. However, males reproduced as soon as they reached sexual maturity (i.e.
      ten months of age) in the urban population, whereas most males delayed
      reproduction to age three years in the rural population.

PMID- 10902545
TI  - Cryptic female choice: frogs reduce clutch size when amplexed by undesired males.
AB  - In species with internal fertilization, females can 'cryptically' choose (e.g.
      through sperm selection) which individuals sire their offspring, even when their
      overt preferences for copulatory partners are overrun by male-male competition
      and sexual coercion. The experiment presented here reveals that control of
      paternity after copulation has begun is also possible in species with external
      fertilization. Females of the hybridogenetic Rana essonae-Rana esculenta (LL-LR)
      waterfrog complex adjust their clutch size in response to mate type: they release
      fewer eggs when amplexed by hybrid LR males who--jeopardize successful
      reproduction--than when amplexed by parental LL males. This reduction in the
      number of eggs laid can increase a female's residual reproductive value through a
      second mating in the same breeding season or a larger clutch size in the next
      year. We argue that cryptic female choice through clutch size adjustment (i) may
      have evolved more often than previously assumed, and (ii) can arise even where
      females mate only once during a reproductive period.

PMID- 10902546
TI  - The impact of predation on burrow use by arctic ground squirrels in the boreal
      forest.
AB  - In sedentary animals, the choice of a suitable home site is critical to survival
      and reproductive fitness. However, habitat suitability may vary with predation
      risk. We compared habitat use of Arctic ground squirrels (Spermophilus parryii
      plesius) living in the boreal forest under conditions of fluctuating predation
      pressure. In our study area, predators show ten-year cycles in numbers that track
      that of their primary prey, the snowshoe hare (Lepus americanus). In 1993, we
      compared burrows that continued to be occupied following the period of intense
      predation during the hare decline of 1990-1992 with those that became vacant, and
      with random locations. We contrasted these sites to those in a predator exclosure
      where predation pressure was minimized. Burrows on control sites were located on
      sloped sites with high visibility. Burrows that remained occupied during the
      period of intense predation were more likely to be in open areas with fewer
      fallen trees than burrows that became vacant. We used discriminant functions
      derived from the control sites and found that 89% of the burrows on the predator
      exclosure were classified as being similar to the random locations on control
      sites. We conclude that the distribution of Arctic ground squirrels in the boreal
      forest is a direct function of predator presence.

PMID- 10902547
TI  - An error limit for the evolution of language.
AB  - On the evolutionary trajectory that led to human language there must have been a
      transition from a fairly limited to an essentially unlimited communication
      system. The structure of modern human languages reveals at least two steps that
      are required for such a transition: in all languages (i) a small number of
      phonemes are used to generate a large number of words; and (ii) a large number of
      words are used to a produce an unlimited number of sentences. The first (and
      simpler) step is the topic of the current paper. We study the evolution of
      communication in the presence of errors and show that this limits the number of
      objects (or concepts) that can be described by a simple communication system. The
      evolutionary optimum is achieved by using only a small number of signals to
      describe a few valuable concepts. Adding more signals does not increase the
      fitness of a language. This represents an error limit for the evolution of
      communication. We show that this error limit can be overcome by combining signals
      (phonemes) into words. The transition from an analogue to a digital system was a
      necessary step toward the evolution of human language.

PMID- 10902548
TI  - With the expectation that cancer detection and treatment will occur increasingly
      at the molecular and gene levels, medical physics trainees should take courses in
      molecular biology and genetics.

PMID- 10902549
TI  - American radium engenders telecurie therapy during World War I.
AB  - From 1899 to 1912 there was a European monopoly controlling the sale of radium
      for cancer therapy. This trust was finally broken, albeit only temporarily, in
      1912/13 by American entrepreneurs J. Flannery, H. Kelly, and J. Douglas. Joe
      Flannery was a former mortician turned mining magnate. Dr. Howard Kelly was the
      renowned gynecological surgeon at Johns Hopkins Hospital and Medical School who
      defied tradition by maintaining his own private hospital. Professor James Douglas
      was the Arizona copper king who helped support Memorial Hospital in New York City
      as America's first cancer hospital. During 1913-1916 surgeons Howard Kelly
      (Baltimore) and H. H. Janeway (Memorial Hospital) began using radium and radon
      for the treatment of deep seated cancers. Their technique required placement of
      the sources several centimeters away from the skin surface. As this new concept,
      telecurie therapy, resulted in a significant decrease in dose rate, it was
      necessary for both surgeons to have several grams of radium, costing
      $180000/gram, in their possession. Fortunately, Kelly and Janeway were the sole
      beneficiaries of a radium mining company, the National Radium Institute, from
      1913 to 1916. With this unique American source of radium and with Europe
      otherwise preoccupied, these two American surgeons pioneered megavoltage
      telecurie therapy, using the 1.2 MeV gamma rays of "mass radium."

PMID- 10902550
TI  - Clinical reference dosimetry: comparison between AAPM TG-21 and TG-51 protocols.
AB  - We compare the results of absorbed dose determined at reference conditions
      according to the AAPM TG-21 dose calibration protocol and the new AAPM TG-51
      protocol. The AAPM TG-21 protocol for absorbed dose calibration is based on
      ionization chambers having exposure calibration factors for 60Co gamma rays,
      N(x). The new AAPM TG-51 dosimetry protocol for absorbed dose calibration is
      based on ionization chambers having 60Co absorbed dose-to-water calibration
      factor, N60Co(D,w). This study shows that the dose changes are within 1% for a
      cobalt beam, 0.5% for photon energies of 6 and 18 MV, and 2%-3% for electron
      beams with energies of 6 to 20 MeV. The chamber primary calibration factors, Nx
      and N60Co(D,w), are traceable to the Canadian primary standards laboratory
      (NRCC). We also present estimated dose changes between the two protocols when
      calibration factors are traceable to NIST in the United States.

PMID- 10902551
TI  - The impact of fluctuations in intensity patterns on the number of monitor units
      and the quality and accuracy of intensity modulated radiotherapy.
AB  - The purpose of this work is to examine the potential impact of the frequency and
      amplitude of fluctuations ("complexity") in intensity distributions on intensity
      modulated radiotherapy (IMRT) dose distributions. The intensity-modulated beams
      are efficiently delivered using a multileaf collimator (MLC). Radiation may be
      delivered through a continuous (dynamic mode) or discrete (step-and-shoot)
      sequence of windows formed by the leaves. Algorithms and software that convert
      optimized intensity distributions into leaf trajectories apply approximate
      empirical corrections to account for the various effects associated with MLC
      characteristics, such as the rounded leaf tips, tongue-and-groove leaf design,
      leaf transmission, leaf scatter, and collimator scatter upstream from the MLC.
      Typically, the difference between inter- and intraleaf transmissions is ignored.
      In this paper, using a schematic example of IMRT for head and neck carcinomas, we
      demonstrate that complex anatomy and severe optimization constraints produce
      complex intensity patterns. Using idealized intensity patterns we also
      demonstrate that, for complex intensity patterns, the average window width tends
      to be smaller and, for the same dose received by the tumor, the number of MUs is
      larger. We found that as the complexity increases, so does the contribution of
      radiation transmitted through and scattered from the leaves ("indirect
      radiation") to the total delivered dose. As a consequence, the lowest deliverable
      intensity in complex intensity patterns may be significantly greater than that
      required to provide adequate protection for some normal tissues. Furthermore,
      since corrections for leaf transmission and scatter effects are approximate and
      the difference between inter- and intraleaf transmission is ignored, the accuracy
      of the delivered dose may be affected. Using the results of a simple experiment
      and a typical intensity-modulated beam for a head and neck case as examples, we
      show the effect of window width and complexity on the accuracy and deliverability
      of intensity patterns. Some possible strategies for improving the accuracy and
      for relaxing the lower limit on deliverable intensity are discussed.

PMID- 10902552
TI  - Beam orientation optimization in intensity-modulated radiation treatment
      planning.
AB  - Beam direction optimization is an important problem in radiation therapy. In
      intensity modulated radiation therapy (IMRT), the difficulty for computer
      optimization of the beam directions arises from the fact that they are coupled
      with the intensity profiles of the incident beams. In order to obtain the optimal
      incident beam directions using iterative or stochastic methods, the beam profiles
      ought to be optimized after every change of beam configuration. In this paper we
      report an effective algorithm to optimize gantry angles for IMRT. In our
      calculation the gantry angles and the beam profiles (beamlet weights) were
      treated as two separate groups of variables. The gantry angles were sampled
      according to a simulated annealing algorithm. For each sampled beam
      configuration, beam profile calculation was done using a fast filtered
      backprojection (FBP) method. Simulated annealing was also used for beam profile
      optimization to examine the performance of the FBP for beam orientation
      optimization. Relative importance factors were incorporated into the objective
      function to control the relative importance of the target and the sensitive
      structures. Minimization of the objective function resulted in the best possible
      beam orientations and beam profiles judged by the given objective function. The
      algorithm was applied to several model problems and the results showed that the
      approach has potential for IMRT applications.

PMID- 10902553
TI  - Intensity modulated radiotherapy with charged particle beams: studies of inverse
      treatment planning for rotation therapy.
AB  - The optimization of intensity modulated radiotherapy (IMRT) for charged particle
      beams is a necessary prerequisite to evaluate the clinical potential of this
      treatment modality in comparison to IMRT with high energy photons. A theoretical
      study for IMRT with charged particle beams delivered by rotation therapy is
      presented. First, the inverse problem for two-dimensional rotation therapy with
      arbitrary depth dose curves is formulated. Then a numerical strategy is devised
      to calculate fluence profiles for the simplified case of arbitrary rotationally
      invariant dose distributions. This mathematical framework is applied to study
      various aspects of charged particle IMRT. A central topic of the investigation is
      the evaluation of dose delivery, based on distal edge tracking (DET) and
      intensity modulation. The potential of DET-IMRT with charged particle beams is
      studied in comparison to an optimal, conventional dose delivery technique, which
      employs the concept of a spread-out Bragg peak (SOBP). Moreover, a comparison to
      photon IMRT is provided for simple geometric dose patterns. The technique of DET
      IMRT for the delivery of a homogeneous target dose is only feasible for targets
      up to a critical radius, depending on the individual shape of the employed Bragg
      peak. The irradiation of larger targets requires energy modulation in addition to
      the range modulation for DET. The accurate placement of the Bragg peak with
      respect to the target edge is found to be of potential importance. Comparing dose
      delivery via DET-IMRT with the optimal SOBP technique revealed a significant
      advantage of DET-IMRT, especially a saved integral dose in target-adjacent
      healthy tissues of up to 30%, and a reduction of the penumbra at the target edge
      by almost 50%. A saving in integral dose to healthy tissues by a factor of 2-3
      was observed for DET-IMRT in comparison to IMRT with high energy photons.

PMID- 10902554
TI  - An analysis of the relationship between radiosensitivity and volume effects in
      tumor control probability modeling.
AB  - The dependence of local tumor control probability (tcp) on tumor volume is
      analyzed and discussed with the help of radiobiological modeling; in particular
      the impact of possible correlations between mean tumor radiosensitivity and tumor
      dimensions on the tcp volume dependence is explored. The linear-quadratic
      Poissonian tumor control probability (tcp) model was modified to account for the
      possible dependence of clonogenic cell density and radiosensitivity parameters on
      tumor volume; then the original and modified versions of the model were fitted to
      published clinical and laboratory tumor control data. These different versions of
      the tcp model often fitted tumor control data equally well, because of the high
      degree of correlation between the parameters. Nevertheless the results were very
      different from a physical point of view and we suggest that sometimes it is
      possible to choose between equally good fits on the basis of physical
      considerations. Possible links between the volume dependence of the mean
      radiosensitivity and the degree of tumor hypoxia were also analyzed through a
      comparison of the results of the tcp fit to published measurements of oxygen
      tension in tumors.

PMID- 10902555
TI  - The impact of electron transport on the accuracy of computed dose.
AB  - The aim of this work was to investigate the accuracy of dose predicted by a Batho
      power law correction, and two models which account for electron range: A
      superposition/convolution algorithm and a Monte Carlo algorithm. The results of
      these models were compared in phantoms with cavities and low-density
      inhomogeneities. An idealized geometry was considered with inhomogeneities
      represented by regions of air and lung equivalent material. Measurements were
      performed with a parallel plate ionization chamber, thin TLDs (thermoluminescent
      dosimeters) and film. Dose calculations were done with a generalized Batho model,
      the Pinnacle collapsed cone convolution model (CCC), and the Peregrine Monte
      Carlo dose calculation algorithm. Absolute central axis and off axis dose data at
      various depths relative to interfaces of inhomogeneities were compared. Our
      results confirm that for a Batho correction, dose errors in the calculated depth
      dose arise from the neglect of electron transport. This effect increases as the
      field size decreases, as the density of the inhomogeneity decreases, and with the
      energy of incident photons. The CCC calculations were closer to measurements than
      the Batho model, but significant discrepancies remain. Monte Carlo results agree
      with measurements within the measurement and computational uncertainties.

PMID- 10902556
TI  - Experimental measurements of dosimetric parameters on the transverse axis of a
      new 125I source.
AB  - Permanent prostate implant using 125I or 103Pd sources is a common treatment
      choice in the management of early prostate cancer. As sources of new designs are
      developed and marketed for application in permanent prostate implants, it is of
      paramount importance that their dosimetric characteristics are carefully
      determined, in order to maintain a high accuracy of patient treatment. This
      report presents the results of experimental measurements of the dosimetric
      parameters performed for a newly available 125I seed source, the model MED3631
      A/M source (IoGold), manufactured by North American Scientific, Inc. The
      measurements were performed in a large scanning water phantom, using a diode
      detector. The positioning of the source and the diode detector was achieved by a
      computer-controlled positioning mechanism in the scanning water phantom. The dose
      rate constant in water for the new 125I source was measured in comparison with an
      existing 125I source of similar design and verified using thermoluminescent
      dosimetry (TLD) measurement. The radial dose function values for the source were
      measured using the diode detector. The measurement technique and the results are
      compared with the dose distribution parameters for the 125I sources discussed in
      the AAPM TG43 report and elsewhere [Med. Phys. 26, 570-573 (1999)]. For the dose
      rate constant in water of the new source, it is recommended that a value of 0.950
      cGy/U-hr be used based on the NIST 1985 air-kerma strength calibration standard,
      or 1.060 cGy/U-hr based on the 1999 NIST air-kerma strength standard. The
      measured radial dose function values for the MED3631-A/M source agree closely
      with those of the model 6702 source. It is therefore recommended that the radial
      dose function values for the model 6702 125I source, as recommended by the AAPM
      TG43 report, be adopted for the new source as well.

PMID- 10902557
TI  - Feasibility of linear arrays for interstitial ultrasound thermal therapy.
AB  - The feasibility of linear array transducers for interstitial ultrasound thermal
      therapy was evaluated. Theoretical acoustic power distributions were used to
      calculate spatial heating patterns using the bioheat transfer equation. The
      spatial heating patterns of linear array and single element planar rectangular
      transducers were compared. Scanned heating with both transducer geometries
      produced asymmetric heating volumes; however, a more uniform radial temperature
      profile with a sharper margin was achieved with linear arrays. Single element
      transducers produced excessive heating near the probe surface. Homogeneous blood
      flow is predicted to reduce the mean temperature within the heated region, with
      little effect on the spatial pattern.

PMID- 10902558
TI  - In vivo dosimetry: intercomparison between p-type based and n-type based diodes
      for the 16-25 MV energy range.
AB  - This paper compares two different types of diodes designed to cover the energy
      range from 16 to 25 MV, one n-type (diode-A) and the other p-type (diode-B). A 18
      MV x-ray beam has been used for all tests. Signal stability postirradiation,
      intrinsic precision and linearity of response with dose, front-back symmetry, and
      dose decrease under the diode were studied. Also, the water equivalent thickness
      of the build up caps was determined. Both types of diodes were calibrated to give
      entrance dose. Entrance correction factors for field size, tray, source skin
      distance, angle, and wedge were determined. Finally, the effect of dose rate,
      temperature and accumulated dose on the diode's response were studied. Only diode
      A had full build-up for 18 MV x rays and standard irradiation conditions. Field
      size correction factor was about 2%-4% for field sizes bigger than 20 x 20 cm2
      for both diodes. Tray correction factor was negligible for diode-A while diode-B
      would overestimate the dose by a 2% for a 40 x 40 cm2 field size if the
      correction factor was not applied. Wedge correction factors are only relevant for
      the 60 degrees wedge, being the correction factor for diode-A significantly
      higher than for diode-B. Diode-A showed less temperature dependence than diode-B.
      Sensitivity dependence on dose per pulse was a 1.5% higher for diode-A than for
      diode-B and therefore a higher SSD dependence was found for diode-A. The loss of
      sensitivity with accumulated radiation dose was only about 0.3% for diode-A,
      after 300 Gy, while it amounted to 8% for diode-B. Weighing the different
      correction factors for both types of diodes no conclusions about which type is
      better can be driven. From these results it can be also seen that the dependence
      of the diode response on dose rate in a pulsed beam does not seem to be
      associated with the fact of being n-type or p-type but could be related to the
      doping level of the diodes.

PMID- 10902559
TI  - Monte Carlo validation in diagnostic radiological imaging.
AB  - Monte Carlo analysis in the radiological sciences has been used for several
      decades, however with the ever-increasing power of desktop computers, the utility
      of Monte Carlo simulation is increasing. A Monte Carlo code called the Simple
      Investigative Environment for Radiological Research Applications (SIERRA) is
      described mathematically, and is then compared against an array of published and
      unpublished results determined by other means. A series of 32 comparisons between
      data sets, 22 from independent Monte Carlo simulations and 10 from physically
      measured data, were assessed. The compared parameters included depth dose curves,
      lateral energy scattering profiles, scatter to primary ratios, normalized
      glandular doses, angular scattering distributions, and computed tomography dose
      index (CTDI) values. Three of the 32 comparison data sets were excluded as they
      were identified as outliers. Of the remaining 29 data sets compared, the mean
      differences ranged from -14.8% to +17.2%, and the average of the mean differences
      was 0.12% (sigma = 1.64%), and the median difference was 1.57%. Fifty percent of
      the comparisons showed mean differences of approximately 5% or less, and 93% of
      the comparisons showed mean differences of 12% or less. We conclude that for
      research applications in diagnostic radiology, the SIERRA Monte Carlo code
      demonstrates accuracy and precision to well within acceptable levels.

PMID- 10902560
TI  - Stereomammography: evaluation of depth perception using a virtual 3D cursor.
AB  - We are evaluating the usefulness of stereomammography in improving breast cancer
      diagnosis. One area that we are investigating is whether the improved depth
      perception associated with stereomammography might be significantly enhanced with
      the use of a virtual 3D cursor. A study was performed to evaluate the accuracy of
      absolute depth measurements made in stereomammograms with such a cursor. A biopsy
      unit was used to produce digital stereo images of a phantom containing 50 low
      contrast fibrils (0.5 mm diam monofilaments) at depths ranging from 1 to 11 mm,
      with a minimum spacing of 2 mm. Half of the fibrils were oriented perpendicular
      (vertical) and half parallel (horizontal) to the stereo shift direction. The
      depth and orientation of each fibril were randomized, and the horizontal and
      vertical fibrils crossed, simulating overlapping structures in a breast image.
      Left and right eye images were generated by shifting the x-ray tube from +2.5
      degrees to -2.5 degrees relative to the image receptor. Three observers viewed
      these images on a computer display with stereo glasses and adjusted the position
      of a cross-shaped virtual cursor to best match the perceived location of each
      fibril. The x, y, and z positions of the cursor were indicated on the display.
      The z (depth) coordinate was separately calibrated using known positions of
      fibrils in the phantom. The observers analyzed images of two configurations of
      the phantom. Thus, each observer made 50 vertical filament depth measurements and
      50 horizontal filament depth measurements. These measurements were compared with
      the true depths. The correlation coefficients between the measured and true
      depths of the vertically oriented fibrils for the three observers were 0.99,
      0.97, and 0.89 with standard errors of the estimates of 0.39 mm, 0.83 mm, and
      1.33 mm, respectively. Corresponding values for the horizontally oriented fibrils
      were 0.91, 0.28, and 0.08, and 1.87 mm, 4.19 mm, and 3.13 mm. All observers could
      estimate the absolute depths of vertically oriented objects fairly accurately in
      digital stereomammograms; however, only one observer was able to accurately
      estimate the depths of horizontally oriented objects. This may relate to
      different aptitudes for stereoscopic visualization. The orientations of most
      objects in actual mammograms are combinations of horizontal and vertical. Further
      studies are planned to evaluate absolute depth measurements of fibrils oriented
      at various intermediate angles and of objects of different shapes. The effects of
      the shape and contrast of the virtual cursor and the stereo shift angle on the
      accuracy of the depth measurements will also be investigated.

PMID- 10902561
TI  - Cone-beam computed tomography with a flat-panel imager: initial performance
      characterization.
AB  - The development and performance of a system for x-ray cone-beam computed
      tomography (CBCT) using an indirect-detection flat-panel imager (FPI) is
      presented. Developed as a bench-top prototype for initial investigation of FPI
      based CBCT for bone and soft-tissue localization in radiotherapy, the system
      provides fully three-dimensional volumetric image data from projections acquired
      during a single rotation. The system employs a 512 x 512 active matrix of a-Si:H
      thin-film transistors and photodiodes in combination with a luminescent phosphor.
      Tomographic imaging performance is quantified in terms of response uniformity,
      response linearity, voxel noise, noise-power spectrum (NPS), and modulation
      transfer function (MTF), each in comparison to the performance measured on a
      conventional CT scanner. For the geometry employed and the objects considered,
      response is uniform to within 2% and linear within 1%. Voxel noise, at a level of
      approximately 20 HU, is comparable to the conventional CT scanner. NPS and MTF
      results highlight the frequency-dependent transfer characteristics, confirming
      that the CBCT system can provide high spatial resolution and does not suffer
      greatly from additive noise levels. For larger objects and/or low exposures,
      additive noise levels must be reduced to maintain high performance. Imaging
      studies of a low-contrast phantom and a small animal (a euthanized rat)
      qualitatively demonstrate excellent soft-tissue visibility and high spatial
      resolution. Image quality appears comparable or superior to that of the
      conventional scanner. These quantitative and qualitative results clearly
      demonstrate the potential of CBCT systems based upon flat-panel imagers. Advances
      in FPI technology (e.g., improved x-ray converters and enhanced electronics) are
      anticipated to allow high-performance FPI-based CBCT for medical imaging. General
      and specific requirements of kilovoltage CBCT systems are discussed, and the
      applicability of FPI-based CBCT systems to tomographic localization and image
      guidance for radiotherapy is considered.

PMID- 10902562
TI  - Performance of a 41X41-cm2 amorphous silicon flat panel x-ray detector for
      radiographic imaging applications.
AB  - We report the performance of a 41 X 41-cm2 amorphous silicon-based flat panel
      detector designed for radiographic imaging applications. The detector consists of
      an array of photodiodes and thin film transistor switches on a 0.2-mm pitch with
      an overlying thallium-doped cesium iodide scintillator. The performance of the
      detector was evaluated through measurement of the frequency-dependent detective
      quantum efficiency [DQE(f)]. Measurements of the characteristic curve and
      modulation transfer function (MTF) are also reported. All measurements were made
      in a radiographic imaging mode with a readout time of 125 ms. We evaluated a
      total of 15 detectors. One detector was characterized at a range of exposures and
      at three different electronic gain settings. Measurements of DQE(f) and MTF were
      also performed as a function of position on one detector. The measured DQE at an
      exposure of about 1 mR was 0.66 at zero spatial frequency and fell smoothly with
      frequency to a value of 0.24 at the Nyquist frequency, 2.5 cycles/mm. The DQE is
      independent of exposure for exposures in the upper 80% of each gain range, but is
      reduced somewhat at lower exposures because of the influence of additive system
      noise. The reduction can be controlled by adjusting the electronic gain. For a
      gain that allows a maximum exposure of 5 mR, the DQE at 0.056 mR was 0.64 at zero
      frequency and 0.19 at 2.5 cycles/mm. The standard deviation in DQE among
      measurements on different detectors was less than 0.02 at any frequency. The
      presampling MTF was 0.26 at 2.5 cycles/mm. The standard deviation in MTF among
      measurements on different detectors was less than 0.01 at any frequency. Both MTF
      and DQE were substantially independent of position on the detector.

PMID- 10902563
TI  - Accuracy and variability assessment of a semiautomatic technique for segmentation
      of the carotid arteries from three-dimensional ultrasound images.
AB  - In this paper, we report on a semiautomatic method for segmentation of three
      dimensional (3D) carotid vascular ultrasound (US) images. Our method is based on
      a dynamic balloon model represented by a triangulated mesh. The mesh is manually
      placed within the interior of the carotid vessels, then is driven outward until
      it reaches the vessel wall by applying an inflation force to the mesh. Once the
      mesh is in close proximity to the vessel wall, it is further deformed using an
      image-based force, in order to better localize the boundary. Since the method
      requires manual initialization, there is inherent variability in the position and
      shape of the final segmented boundary. Using a 3D US image of a patient's
      carotids, we have examined the local variability in boundary position as the
      initialization position is varied throughout the interior of the carotid vessels
      in the 3D image. We have compared the semiautomatic segmentation method to a
      fully manual segmentation method, and found that the semiautomatic approach is
      less variable than the intraobserver variability for manual segmentation. We have
      furthermore examined the accuracy of the semiautomatic method by comparing the
      average surface to an "ideal" surface, determined by the average manually
      segmented surface. We have found, in general, good agreement between the
      semiautomatic and manual segmentation methods. For the 3D US image in question,
      the mean separation between the average segmented surface and the gold standard
      was found to be 0.35 mm. The two surfaces were determined to agree with each
      other, within uncertainty, at 65% of the mesh points comprising the two surfaces.

PMID- 10902564
TI  - International Congresses of Biochemistry--personal recollections.

PMID- 10902566
TI  - Regulation of DNA replication during the cell cycle: roles of Cdc7 kinase and
      coupling of replication, recombination, and repair in response to replication
      fork arrest.
AB  - DNA replication is central to cell growth, development, and generation of tissues
      and organs. Recent advances in understanding replication machinery have revealed
      striking conservation of components involved in the processes of DNA replication,
      from yeasts to human. The conservation extends even to bacteria for some basic
      components of replication apparatus. Eukaryotic DNA replication is regulated at
      various stages to ensure strict regulation during cell cycle. We have identified
      a novel mammalian kinase, Cdc7-ASK (Activator of S phase Kinase), that plays a
      key role at the entry into S phase as a molecular switch for DNA replication.
      This kinase is specifically activated during S phase and triggers the firing of
      DNA replication by phosphorylating an essential DNA helicase component of the
      replication complex. Environmental stresses such as DNA damages or depletion of
      essential nutrients for DNA synthesis lead to unscheduled arrest of DNA
      replication forks. In bacteria, this leads to induction of altered modes of DNA
      replication, which may repair DNA damages, facilitate reassembly of replication
      machinery at the stalled replication fork, or do both. In eukaryotes, blocking
      replication forks usually induces both checkpoint responses, which prevent
      premature progression of cell cycle events before precise completion of the
      preceding cell cycle stage, and the recombinational repair system for the
      lesions. Possible common bases in recognition of stalled replication forks in
      bacteria and eukaryotes will be discussed. Furthermore, we will discuss the
      potential of replication and checkpoint proteins as targets of anticancer agents
      as well as possible novel technology for stem cell amplification through
      manipulation of DNA replication.

PMID- 10902565
TI  - Pseudouridine in RNA: what, where, how, and why.
AB  - Pseudouridine (5-ribosyluracil) is a ubiquitous yet enigmatic constituent of
      structural RNAs (transfer, ribosomal, small nuclear, and small nucleolar).
      Although pseudouridine (psi) was the first modified nucleoside to be discovered
      in RNA, and is the most abundant, its biosynthesis and biological roles have
      remained poorly understood since its identification as a "fifth nucleoside" in
      RNA. Recently, a combination of biochemical, biophysical, and genetic approaches
      has helped to illuminate the structural consequences of psi in
      polyribonucleotides, the biochemical mechanism of U-->psi isomerization in RNA,
      and the role of modification enzymes (psi synthases) and box H/ACA snoRNAs, a
      class of eukaryotic small nucleolar RNAs, in the site-specific biosynthesis of
      psi. Through its unique ability to coordinate a structural water molecule via its
      free N1-H, psi exerts a subtle but significant "rigidifying" influence on the
      nearby sugar-phosphate backbone and also enhances base stacking. These effects
      may underlie the biological role of most (but perhaps not all) of the psi
      residues in RNA. Certain genetic mutants lacking specific psi residues in tRNA or
      rRNA exhibit difficulties in translation, display slow growth rates, and fail to
      compete effectively with wild-type strains in mixed culture. In particular,
      normal growth is severely compromised in an Escherichia coli mutant deficient in
      a pseudouridine synthase responsible for the formation of three closely spaced
      psi residues in the mRNA decoding region of the 23S rRNA. Such studies
      demonstrate that pseudouridylation of RNA confers an important selective
      advantage in a natural biological context.

PMID- 10902567
TI  - Mitochondria in the programmed death phenomena; a principle of biology: "it is
      better to die than to be wrong".
AB  - The very fact that mitochondria participate in amplification of the cell suicide
      signals has stimulated interest in the mechanism of this and related phenomena.
      It seems probable that mitochondria possess an autonomic system that allows them
      to commit suicide. This mitoptosis is mediated by reactive oxygen species (ROS),
      causing opening of the permeability transition pores (PTP) in the inner
      mitochondrial membrane. Mitoptosis can purify the mitochondrial population in a
      cell from the ROS-overproducing organelles. Massive mitoptosis can result in
      apoptosis (programmed cell death) because of the release of proapoptotic proteins
      from the mitochondrial intermembrane space, a mechanism purifying tissues from
      the ROS-overproducing and other unwanted cells. Large-scale apoptosis can be used
      by organisms to eliminate some organs during ontogenesis (organoptosis). In adult
      organisms, organoptosis of organs of vital importance may entail a programmed
      death of individuals (phenoptosis). This mechanism might purify kins,
      communities, and populations from individuals becoming dangerous because of, for
      example, heavy infection (septic shock). It is hypothesized that aging represents
      a slow ROS-linked phenoptosis that eliminates individuals with damaged genomes
      and gives reproductive advantage to those who succeeded in a better preservation
      of their genomes from damage.

PMID- 10902568
TI  - Imaging signal transduction in living cells with GFP-based probes.
AB  - Since the cloning and the eterologous expression of the Green Fluorescence
      Protein (GFP), a number of applications have been reported where protein location
      within the cell or gene expression is revealed by fluorescent imaging of living
      cells. Modified GFPs, however, can now be exploited not only as a fluorescent
      reporter but also as a dynamic marker of intracellular signalling events, such as
      fluctuations in the levels of the second messengers Ca2+ and cAMP, or as a probe
      for detecting changes in pH in various cell compartments. These genetically
      manipulated GFPs allow monitoring of the biochemistry of the cell in real time
      and thus offer the possibility to gain a more precise view of the functioning of
      live cells.

PMID- 10902569
TI  - Redox regulation of lymphocyte signaling.
AB  - Compelling evidence exists that reactive oxygen species can deliver intracellular
      signals in mammalian cells, and elicit a broad array of physiological responses
      according to the cell type, the oxidative burden and the cellular compartment
      where radicals are generated. When applied to immune cells, these concepts gain a
      particular relevance, in relation to the plasticity of immune functions and the
      biological complexity of lymphocyte response to antigens. Here we review some
      recent and somehow conflicting observations on the involvement of oxygen radicals
      and redox balance in lymphocyte activation, and propose models for how radical
      species could contribute to normal and pathological immunity.

PMID- 10902570
TI  - What couples glycolysis to mitochondrial signal generation in glucose-stimulated
      insulin secretion?
AB  - Pancreatic islet beta-cells are poised to generate metabolic messengers in the
      mitochondria that link glucose metabolism to insulin exocytosis. This is
      accomplished through the tight coupling of glycolysis to mitochondrial
      activation. The messenger molecules ATP and glutamate are produced after the
      metabolism of glycolysis-derived pyruvate in the mitochondria. The entry of
      monocarboxylates such as pyruvate into the beta cell is limited, explaining why
      overexpression of monocarboxylate transporters unravels pyruvate-stimulated
      insulin secretion. NADH generated by glycolysis is efficiently reoxidized by
      highly active mitochondrial shuttles rather than by lactate dehydrogenase.
      Overexpression of this enzyme does not alter glucose-stimulated insulin
      secretion, suggesting that NADH availability restricts the conversion of pyruvate
      to lactate in the beta cell. These metabolic features permit the fuel function of
      glucose to be extended to the generation of signaling molecules, which increases
      cytosolic Ca2+ and promotes insulin exocytosis.

PMID- 10902571
TI  - Scavenger receptors and modified lipoproteins: fatal attractions?
AB  - Lipoproteins modified by oxidation, glycation, alkylation, and nitration are
      generated by oxidative stress during inflammation, diabetes, and inadequate
      supply of dietary antioxidants. A family of genes, the scavenger receptors,
      recognizes and internalizes modified lipoproteins, making them susceptible to
      degradation. Clearance of modified lipoproteins by scavenger receptors occurs
      mainly in macrophages, dendritic cells, and Kupffer cells of the liver. However,
      scavenger receptor expression also occurs in other cells, such as endothelial
      cells, aortic smooth muscle cells, neuronal cells, and keratinocytes. Thus, the
      local clearance of oxidized low-density lipoprotein and the resolution of
      inflammatory processes may rely in part on the expression of scavenger receptors
      in "nonprofessional" phagocytes. Uptake of oxidized low-density lipoprotein,
      without an efficient machinery to degrade them and uncontrolled expression of
      scavenger receptors, may lead to cellular deregulation, apoptosis, and formation
      of foam cells. Diseases accompanied by oxidation of lipoproteins, such as
      atherosclerosis, Alzheimer disease, glomerulosclerosis, ataxia with vitamin E
      deficiency, and possibly age-dependent lipofuscin deposition, may share a common
      pathogenetic feature. This review will focus on foam cell formation, mainly
      within the atherosclerotic lesion, and the possible involvement of aberrant
      regulation of the scavenger receptor genes. To date, the regulatory mechanisms at
      the basis of scavenger receptor gene expression and their roles in
      atherosclerosis and other diseases are not well established. Knowledge on this
      subject could lead to a better understanding of the pathogenesis, prevention, and
      therapy of these diseases.

PMID- 10902573
TI  - Selenium, the element of the moon, in life on earth.
AB  - The present status of selenium biochemistry is reviewed with particular emphasis
      on biomedical problems related to the selenium status of humans and experimental
      animals. Historical milestones of selenium biochemistry starting from the
      identification of the first selenoenzymes up to the elucidation of prokaryotic
      and eukaryotic selenoprotein biosynthesis are compiled. Topical hypotheses on the
      biological role of selenium in general and of individual selenoproteins in
      respect to antioxidant defense, redox regulation of metabolic processes, thyroid
      function, spermatogenesis, oncogenesis, and atherogenesis are critically
      evaluated.

PMID- 10902572
TI  - Epidermal growth factor receptor signal transactivation.
AB  - Cross-communication between heterologous signaling systems and the epidermal
      growth factor receptor (EGFR) has been shown to be critical for a variety of
      biological responses: EGFR transactivation when G-protein-coupled receptors
      (GPCRs) are stimulated represents the paradigm of an interreceptor network that
      is dependent on G-proteins, kinases, metalloproteases, and growth factor
      precursors. Investigating the mechanism of this process will help expand our
      knowledge of physiological regulatory mechanisms and diverse pathophysiological
      disorders.

PMID- 10902574
TI  - Caspase requirement for neuronal apoptosis and neurodegeneration.
AB  - The execution of the apoptotic programme involves a relatively few pathways that
      converge on activation of the caspase family of proteases. However, increasing
      evidence indicates that apoptotic-like features can be found also when cells are
      treated with inhibitors of caspases. This has posed questions as to whether death
      with apoptotic features can still occur in a caspase-independent way, and whether
      caspase inhibitors may then be used to prevent excess apoptosis in disease.
      Metabolic defects, loss of neuronal connectivity and cell loss characterise
      several neurodegenerative diseases. Targeting excessive cell demise may be one
      therapeutic strategy. However, loss of connectivity and neurite regression may
      not be part of the apoptotic programme, and degenerating neurons might use
      multiple execution pathways. In addition, metabolic defects leading to ATP
      depletion can preclude caspase activation and consequently switch execution of
      cell death towards necrosis. The possibility of inhibiting apoptosis as strategy
      to treat neurodegenerative disease is discussed in this review.

PMID- 10902575
TI  - Mitochondrial oxidative stress plays a key role in aging and apoptosis.
AB  - Harman first suggested in 1972 that mitochondria might be the biological clock in
      aging, noting that the rate of oxygen consumption should determine the rate of
      accumulation of mitochondrial damage produced by free radical reactions. Later in
      1980 Miquel and coworkers proposed the mitochondrial theory of cell aging.
      Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen
      radicals that exceed the cellular antioxidant defences. The key role of
      mitochondria in cell aging has been outlined by the degeneration induced in cells
      microinjected with mitochondria isolated from fibroblasts of old rats, especially
      by the inverse relationship reported between the rate of mitochondrial production
      of hydroperoxide and the maximum life span of species. An important change in
      mitochondrial lipid composition is the age-related decrease found in cardiolipin
      content. The concurrent enhancement of lipid peroxidation and oxidative
      modification of proteins in mitochondria further increases mutations and
      oxidative damage to mitochondrial DNA (mtDNA) in the aging process. The
      respiratory enzymes containing the defective mtDNA-encoded protein subunits may
      increase the production of reactive oxygen species, which in turn would aggravate
      the oxidative damage to mitochondria. Moreover, superoxide radicals produced
      during mitochondrial respiration react with nitric oxide inside mitochondria to
      yield damaging peroxynitrite. Treatment with certain antioxidants, such as
      sulphur-containing antioxidants, vitamins C and E, or the Ginkgo biloba extract
      EGb 761, protects against the age-associated oxidative damage to mtDNA and the
      oxidation of mitochondrial glutathione. Moreover, the EGb 761 extract also
      prevents changes in mitochondrial morphology and function associated with aging
      of the brain and liver.

PMID- 10902576
TI  - Quantitative determination of surface concentration of human apolipoprotein H
      with capillary electrophoresis.
AB  - The phospholipid monolayer at an air/water interface is widely used to mimic the
      biological membrane. The dynamic process of the protein or peptide interacting
      with lipid molecules can be reflected in the change in surface pressure of the
      monolayer. But the conventional method used to measure the surface pressure
      change gives results that cannot easily be correlated with the contribution of a
      single protein molecule. Previously, measuring the surface concentration of the
      protein molecules at the air/water interface has required the protein to be
      labeled with radioactivity or fluorescence. Here, a new method using capillary
      electrophoresis is introduced to measure the surface concentration of the
      protein. The results show at least two advantages of the new method: The
      numerical results of protein concentration can be obtained in a more precise and
      rapid way; and there is no need to label the protein sample or to build a special
      monolayer setup.

PMID- 10902577
TI  - Nitric oxide: the "second messenger" of insulin.
AB  - Incubation of various tissues, including heart, liver, kidney, muscle, and
      intestine from mice and erythrocytes or their membrane fractions from humans,
      with physiologic concentration of insulin resulted in the activation of a
      membrane-bound nitric oxide synthase (NOS). Activation of NOS and synthesis of NO
      were stimulated by the binding of insulin to specific receptors on the cell
      surface. A Lineweaver-Burk plot of the enzymatic activity demonstrated that the
      stimulation of NOS by insulin was related to the decrease in the Km for L
      arginine, the substrate for NOS, with a simultaneous increase of Vmax. Addition
      of NG-nitro-L-arginine methyl ester (LNAME), a competitive inhibitor of NOS, to
      the reaction mixture completely inhibited the hormone-stimulated NO synthesis in
      all tissues. Furthermore, NO had an insulin-like effect in stimulating glucose
      transport and glucose oxidation in muscle, a major site for insulin action.
      Addition of NAME to the reaction mixture completely blocked the stimulatory
      effect of insulin by inhibiting both NO production and glucose metabolism,
      without affecting the hormone-stimulated tyrosine or phosphatidyl-inositol 3
      kinases of the membrane preparation. Injection of NO in alloxan-induced diabetic
      mice mimicked the effect of insulin in the control of hyperglycemia (i.e.,
      lowered the glucose content in plasma). However, injection of NAME before the
      administration of insulin to diabetic-induced and nondiabetic mice inhibited not
      only the insulin-stimulated increase of NO in plasma but also the glucose
      lowering effect of insulin.

PMID- 10902578
TI  - Ferritin oxidation in vitro: implication of iron release and degradation by the
      20S proteasome.
AB  - Ferritin, the major iron storage protein in mammalian cells, was treated with
      various concentrations of different oxidants: xanthine/xanthine oxidase, Sin-1 (3
      morpholinosydnonimine, purchased from Alexis, Grunberg, Germany), DEA-NO
      (Diethylamine NONOate, purchased from Calblochem-Novabiochem, Schwalbach,
      Germany), and hydrogen peroxide. The proteolytic susceptibility towards the
      isolated 20S proteasome of untreated ferritin and oxidized ferritin was measured
      in parallel with the iron liberated by these oxidants. With increasing hydrogen
      peroxide, Sin-1, and xanthine oxidase concentrations, the measured proteasomal
      degradation of ferritin also increased. At higher oxidant concentrations,
      however, the proteolytic susceptibility began to decrease. The oxidation of
      ferritin by DEA-NO was accompanied by a lesser increase of proteolytic
      susceptibility in comparison with the effects of the other oxidants. Addition of
      DEA-NO to Sin-1 suppressed the increase in proteolytic susceptibility of
      ferritin, whereas adding xanthine/xanthine oxidase had no additional effect. Iron
      was liberated readily from ferritin as a result of the oxidation process,
      although the increase in proteolytic susceptibility was not always correlated to
      the iron release. In fact, the degradation of oxidatively damaged ferritin was
      not accompanied by a further increase of free iron. Therefore, we conclude that
      the proteasome is a secondary antioxidative defense system that degrades only
      nonfunctional ferritin.

PMID- 10902579
TI  - Sites of binding and orientation in a four-location model for protein
      stereospecificity.
AB  - The stereospecificity of the enzyme isocitrate dehydrogenase was examined by
      steady-state kinetics and x-ray crystallography. The enzyme has the intriguing
      property that the apoenzyme in the absence of divalent metal showed a selectivity
      for the inactive l-enantiomer of the substrate isocitrate, whereas the enzyme
      containing magnesium showed selectivity for the physiologically active d
      enantiomer. The hydrogen atom on the C2 carbon that is transferred during the
      reaction was, in both the d- and l-isocitrate complexes, in an orientation very
      close to that expected for delivery of a hydride ion to the cosubstrate NADP+.
      The beta-carboxylate that is eliminated as a CO2 molecule during the reaction
      occupied the same site on the protein in both the d- and l-isocitrate complexes.
      In addition, the C3 carbon was in the same protein site in both the d- and l
      enantiomers. Only the fourth group, the OH atom, was in a very different position
      in the apo enzyme and in the metal-containing complexes. A four-location model is
      necessary to explain the enantiomeric specificity of IDH in contrast to the
      conventional three-point attachment model. The thermodynamic and kinetic
      ramifications of this model are explored.

PMID- 10902580
TI  - Use tests: ROAT (repeated open application test)/PUT (provocative use test): an
      overview.
AB  - As one step in defining the clinical relevance of exposure to an allergen
      identified with patch testing, use tests (provocative use test (PUT), and
      repeated open application test (ROAT)) have been used. In 1/2 of the cases of
      seemingly reliable patch tests, use tests are negative, suggesting that the
      patient's biologic threshold of response had not been reached with open
      application dosing. Dramatic differences exist in regional skin reactivity and
      percutaneous penetration. Negative results of use tests on normal skin may become
      positive on diseased skin. To refine this assay further, more controlled
      observations and analysis of reaction differences between normal and damaged
      skin, and among regional anatomic sites might be performed. In addition, we
      require a standardized measurement for the results. Use testing has significant
      potential in refinement of the evidence-based diagnosis of clinical relevance.
      However, for general validation, we should fill the deficiencies described above.

PMID- 10902581
TI  - The use of protective gloves and the prevalence of hand eczema, skin complaints
      and allergy to natural rubber latex among dental personnel in the county of
      Uppsala, Sweden.
AB  - During the past decade, there has been an increasing problem with acrylate
      allergy and natural rubber latex (NRL) allergy among dental personnel. The aim of
      the present study was to evaluate the prevalence of these problems among
      dentists, dental nurses and dental hygienists in Uppsala county, Sweden. The
      study was based on a self-administered questionnaire sent to 690 persons with 527
      responders (76%). The most common skin problem was dry skin, fissures and/or
      itching on the hands. Of the 72 persons (13.6%) reporting to have suffered from
      hand eczema during the past 12 months, 41 were patch tested with the TRUE Test
      standard series and the Swedish dental screening series. In the patch tested
      group, 9.8% reacted to 1 or more of the acrylates. In addition, 389 persons were
      tested for NRL allergy with the Pharmacia Upjohn CAP-RAST test, and of these, we
      found 7.2% to be positive. The prevalence of self-reported hand eczema and the
      number of positive CAP-RAST tests differed between the 3 occupations, with higher
      figures for the dentists. There was also a correlation between atopic eczema and
      hand eczema. Of those reporting skin symptoms, 67.7% connected them to the place
      of work and 28.8% related them to the use of gloves.

PMID- 10902582
TI  - Allergologically relevant rubber accelerators in single-use medical gloves.
AB  - To prevent contact with specific rubber accelerators, sensitized patients have to
      know in which glove brands these accelerators are present. Additionally,
      quantitative measurements of the bioavailable amounts of accelerators are needed
      to assist consumers in selecting gloves with the lowest possible amount of
      residual rubber accelerators. The aim of the study was to develop an analytical
      method by which residuals of rubber accelerators in single-use medical gloves
      could be determined qualitatively and quantitatively. 19 different glove brands
      were analysed for content of accelerators, and the results were compared to
      manufacturers' ingredient claims of the identical gloves. ZDEC, ZDBC, ZMBT and
      ZPC were the most frequently detected chemicals. In 9 of 15 gloves discrepancies
      were found, usually minor, between content of accelerators declared by
      manufacturers to be present and accelerators detected by analysis. Both phosphate
      buffer and acetone were tested as extraction media. No accelerators were
      detectable with the described chemical analysis in phosphate extracts, whereas
      acetone was demonstrated to be a technically suitable medium for extraction.
      However, more kinetic studies of the extraction procedure and studies of skin
      penetration are needed to document that the extraction procedure simulates the
      clinical situation.

PMID- 10902583
TI  - 4 cases of photocontact dermatitis due to ketoprofen.
AB  - We report 4 cases of photocontact dermatitis due to ketoprofen, a non-steroidal
      anti-inflammatory drug derived from propionic acid. We carried out a skin biopsy
      to examine the amount of ketoprofen in the eruptive skin. We investigated the
      cross-reactions between tiaprofenic acid, suprofen and ketoprofen by patch and
      photopatch testing. In case no. 1, 17 days after the discontinuance of Mohrus
      poultice (containing ketoprofen as an active ingredient), we detected ketoprofen
      312.5 ng/g in the area of skin where the poultice was applied. All 4 cases
      reacted positively to the causative medicaments containing ketoprofen and
      ketoprofen 1% pet. 3 out of 4 cases reacted positively to tiaprofenic acid 1%
      pet. Only 1 case out of the ketoprofen and tiaprofenic acid positive cases
      reacted positively to suprofen 1% pet. Vehicles of patients' medicaments were
      negative in all 4 cases. We suspected that the key structure of the cross
      reaction between ketoprofen and tiaprofenic acid and suprofen was the benzoyl
      radical.

PMID- 10902585
TI  - The trend of nickel allergy from a Scottish tertiary referral centre.
AB  - The aims of this study were to analyze the change in trend of allergic contact
      dermatitis (ACD) from nickel in a single tertiary referral centre. In 1982 and
      1997, 800 and 860 patients were patch tested, respectively. The frequency of
      positive reactions to nickel from our centre was 16% in 1982 and 22% in 1997. In
      both years, the vast majority of patients developed the eruption below 30 years
      of age. However, the commonest age of onset in 1982 was in the 11-20 year age
      group, while in 1997, this was 1 decade later, in the 21-30 year age group. In
      1997, we noted a much higher female preponderance (F:M=13:1) than in 1982
      (F:M=6:1). There was no change in male prevalence but a slight increase in female
      prevalence in 1997. The rate of atopy in patients with nickel ACD showed an
      increase from 23% in 1982 to 33% in 1997. Nickel was thought to be a contributory
      factor in causing occupational dermatitis in 27% of patients in 1982 and 24%
      patients in 1997. Of these, hairdressing in 1982 and nursing in 1997 were the
      commonest occupations. In 1982 and 1997, respectively, 40 (5%) and 37 (4%)
      patients were positive to nickel alone, while 89 (11%) and 150 (18%) patients
      showed positive reactions to other allergens in addition to nickel. In both the
      years, the hands were the main sites of involvement. However, in 1997 there was
      an increase in the number of patients presenting with face and neck involvement.

PMID- 10902584
TI  - Contact allergy to 5,5'-di-tert-butyl-2,2'-dihydroxy-(hydroxymethyl)-dibenzyl
      ethers, sensitizers, in p-tert-butylphenol-formaldehyde resin.
AB  - Allergy to p-tert-butylphenol-formaldehyde resin (PTBP-F-R) is not rare. This
      resin consists of a large number of substances, most of which are still unknown.
      More knowledge about the sensitizers in the resin is a good basis for development
      of diagnosis, treatment and prevention. The aim of this investigation was to
      study allergens in PTBP-F-R by isolation of some medium molecular weight
      substances from the resin and patch testing these in individuals hypersensitive
      to PTBP-F-R. 2 isolated substances were shown to be allergens in PTBP-F-R, 5,5'
      di-tert-butyl-2,2'-dihydroxy-3,3'-dihydroxymethyl-dibenzyl ether and 5,5'-di-tert
      butyl-2,2'-dihydroxy-3-hydroxymethyl-dibenzyl ether. 13 patients hypersensitive
      to PTBP-F-R were patch tested with serial dilutions of 5,5'-di-tert-butyl-2,2'
      dihydroxy-3,3'-dihydroxymethyl-dibenzyl ether and 12 of them reacted positively.
      12 patients hypersensitive to PTBP-F-R were patch tested with serial dilutions of
      5,5'-di-tert-butyl-2,2'-dihydroxy-3-hydroxymethyl-dibenzyl ether and 11 of them
      reacted positively. Positive patch test reactions were seen down to 0.0000025
      mmole x 1(-1) (approximately 0.01 ppm) for both 5,5'-di-tert-butyl-2,2'-dihydroxy
      3,3'-dihydroxymethyl-dibenzyl ether and 5,5'-di-tert-butyl-2,2'-dihydroxy-3
      hydroxymethyl-dibenzyl ether in the most sensitive patient. HPLC analysis of 2
      PTBP-F-Rs showed the presence of 1.0-1.7% w/w 5,5'-di-tert-butyl-2,2'-dihydroxy
      3,3'-dihydroxymethyl-dibenzyl ether and 0.75-0.90% w/w 5,5'-di-tert-butyl-2,2'
      dihydroxy-3-hydroxymethyl-dibenzyl ether in the resins.

PMID- 10902586
TI  - Survey of patch testing in Scotland.
AB  - We have surveyed Scottish dermatologists to establish the extent of patch
      testing, to assess the reasons for referral and to document resources and methods
      used by dermatologists. 104 questionnaires were sent to members of the Scottish
      Dermatological Society. 82 questionnaires (79%) were returned. 50% of respondents
      were consultants, 27% were trainees and 23% held staff grade or clinical
      assistant positions. The mean waiting time for a patch test appointment was 4.5
      months. The most frequent reasons for patch testing were localized eczema, eczema
      not responding to conventional treatment, occupational eczema, history of contact
      sensitivity and eczema of uncertain cause. 17 of 82 respondents (21%) were the
      principal clinicians supervising patch testing in their hospitals. 11 of 17 read
      reactions at 2 and 4 days. Mean time spent on advising patients was 13 min per
      patients. 7 of 17 were dissatisfied with resources available for patient
      education and 16 of 17 felt they would benefit from a central source for patient
      information. Only 4 of 17 centres recorded patch test results on a database and 3
      centres regularly reviewed their patch test results. In conclusion, we have
      identified areas of patch testing that require further improvement.

PMID- 10902587
TI  - Metal-induced generalized pruriginous dermatitis and endovascular surgery.
AB  - Metal contact allergy is a common problem in the general population. Diagnostic
      and therapeutic medical-surgical procedures in which metals can be responsible
      for eczema are diverse. Endovascular aortic surgery is still an experimental but
      less invasive technique. A generalized eczematous dermatitis elicited by metal of
      an endovascular prosthesis is presented. An abdominal aortic aneurysm was
      diagnosed in a 79-year-old woman. Endoluminal repair with a straight Vanguard
      endograft was successful. 3 weeks later, she suffered a severe episode of
      erythema and eczema on the legs. Since then, she complained of continuous
      pruritus with eczema and excoriated papules. The dermatitis and also the patch
      test pathology showed eczema. Patch testing was positive to nickel sulfate and
      cobalt chloride. An endograft semi-quantitative metal analysis was performed with
      plasma-induction joint mass-spectrometry. The self-expanding metal stent was
      mainly composed of nickel (approximately 55%) and titanium (21%) with reinforcing
      thread of platinum. Antimony was detected only in the polyester textile. These
      results are consistent with Nitinol composition. The need for preoperative patch
      testing for metals is controversial. Enquiry about metal allergy is recommended
      before endoluminal surgical procedures. In the near future, the design of
      endografts must take into account the possibility of this sort of reaction.

PMID- 10902588
TI  - Recommendation to include budesonide and tixocortol pivalate in the European
      standard series. ESCD and EECDRG. European Society of Contact Dermatitis.

PMID- 10902589
TI  - Occupational protein contact dermatitis from fruits.

PMID- 10902590
TI  - Occupational airborne allergic contact dermatitis from disperse dyes.

PMID- 10902591
TI  - Occupational allergic contact dermatitis from both 2-bromo-2-nitropropane-1,3
      diol and methylchloroisothiazolinone plus methylisothiazolinone in spin finish.

PMID- 10902592
TI  - Primin-free Primula obconica plants available.

PMID- 10902593
TI  - Contact dermatitis from Chelidonium majus (greater celandine).

PMID- 10902594
TI  - Latent (subclinical) contact dermatitis evolving into occupational allergic
      contact dermatitis from extremely small amounts of epoxy resin.

PMID- 10902595
TI  - Seasonal allergic contact dermatitis from Taraxacum officinale (dandelion) in an
      Israeli florist.

PMID- 10902596
TI  - Occupational allergic contact dermatitis in two aromatherapists.

PMID- 10902597
TI  - Descriptive comparison of isolated hand dermatitis and other populations at St.
      John's Contact Dermatitis Clinic.

PMID- 10902598
TI  - Questions raised by skin reactions observed during squaric acid dibutyl ester
      contact sensitization.

PMID- 10902599
TI  - Asthma, latex hypersensitivity and potatoes.

PMID- 10902600
TI  - Contact allergy to Euxyl K 400 in consecutively patch-tested patients.

PMID- 10902601
TI  - Occupational allergic contact dermatitis from 2,2-bis[4-(2-hydroxy-3
      acryloxypropoxy)phenyl]-propane (epoxy diacrylate) in ultraviolet-cured inks.

PMID- 10902602
TI  - Allergic contact dermatitis due to indomethacin and diclofenac.

PMID- 10902603
TI  - Delayed-type hypersensitivity rash from paracetamol.

PMID- 10902605
TI  - Systemic reaction to glatiramer acetate.

PMID- 10902604
TI  - Polyvinylpyrrolidone (PVP)/eicosene copolymer: an emerging cosmetic allergen.

PMID- 10902606
TI  - Microsatellites in the HLA region: 1999 update.
AB  - In this third update of a series of reviews on microsatellites in the HLA region
      or close to it we report 155 microsatellites, corresponding to 51 newly described
      markers, in addition to the 103 reported in the 1997 and 1998 reviews. This work
      is based both on a literature review and on data publicly available in molecular
      databases on the internet (http://www.gdb.org;
      http://bioinfo.weizmann.ac.il/cards/; http://cedar.genetics.soton.ac.uk/) up to
      September 1999. Thanks to numerous studies involving major histocompatibility
      complex (MHC) microsatellites, documentation on HLA region is proposed, including
      information on microsatellites described through MHC sequence projects and
      presenting documented location, polymorphism and amplification condition,
      together with additional information on previously described microsatellites when
      available and information on data in the literature regarding gametic
      associations between HLA region loci and alleles and microsatellite alleles. As
      basic information are presented various documents: i) a table showing the
      following characteristics of the 155 microsatellites: name, localisation,
      polymorphism, primer sequences, reference; ii) an integrated map of some HLA
      region genes and the 155 microsatellites considered; and iii) a summary table on
      HLA and microsatellites association patterns. In addition, an overview on HLA
      microsatellite analysis application is presented, with a special focus on disease
      genetics studies in the form of recent references where the use of
      microsatellites of the HLA region was a key tool. This review aims at providing
      the human immunogenetics community with a tool for helping optimal choice of
      microsatellites to be used in various studies.

PMID- 10902607
TI  - Comparative reactivity of different HLA-G monoclonal antibodies to soluble HLA-G
      molecules.
AB  - Different HLA-G monoclonal antibodies (mAbs) were first evaluated for their
      capability to identify soluble HLA-G (sHLA-G) in ELISA. Three of them, namely
      87G, BFL.1 and MEM-G/9, when used as coating mAbs together with W6/32 capture
      mAb, identified beta2-microglobulin (beta2m)-associated-sHLA-G but not soluble
      HLA-B7 (sHLA-B7) in cell culture supernatants from transfected cells. By
      comparison, the anti-HLA class I mAb 90 did recognize both sHLA-G and sHLA-B7. By
      using these HLA-G mAbs, sHLA-G was identified in amniotic fluids as well as in
      culture supernatants of first trimester and term placental explants but not in
      cord blood. Intron 4-retaining sHLA-G isoforms were identified in some amniotic
      fluids by the use of an intron 4-specific mAb (16G1). Reactivity of these
      different HLA-G mAbs was then compared to determine their respective binding
      sites on soluble and membrane-bound HLA-G. Using both ELISA and flow cytometry
      analysis, we showed that they did not compete with each other, which suggested
      that they did not recognize the same determinants. Finally, we report that two
      mAbs directed against the alpha1 domain of HLA class I heavy chain (mAb 90 and
      YTH 862) did compete with 87G, therefore demonstrating that this latter mAb
      recognized an epitope localized on this external domain of HLA-G.

PMID- 10902608
TI  - Poor correspondence between predicted and experimental binding of peptides to
      class I MHC molecules.
AB  - Naturally processed peptides presented by class I major histocompatibility
      complex (MHC) molecules display a characteristic allele specific motif of two or
      more essential amino acid side chains, the so-called peptide anchor residues, in
      the context of an 8-10 amino acid long peptide. Knowledge of the peptide binding
      motif of individual class I MHC molecules permits the selection of potential
      peptide antigens from proteins of infectious organisms that could induce
      protective T-cell-mediated immunity. Several methods have been developed for the
      prediction of potential class I MHC binding peptides. One is based on a simple
      scanning for the presence of primary peptide anchor residues in the sequence of
      interest. A more sophisticated technology is the utilization of predictive
      computer algorithms. Here, we have analyzed the experimental binding of 84
      peptides selected on the basis of the presence of peptide binding motifs for
      individual class I MHC molecules. The actual binding was compared with the
      results obtained when analyzing the same peptides by two well-known, publicly
      available computer algorithms. We conclude that there is no strong correlation
      between actual and predicted binding when using predictive computer algorithms.
      Furthermore, we found a high number of false-negatives when using a predictive
      algorithm compared to simple scanning for the presence of primary anchor
      residues. We conclude that the peptide binding assay remains an important step in
      the identification of cytotoxic T lymphocyte (CTL) epitopes which can not be
      substituted by predictive algorithms.

PMID- 10902609
TI  - A PCR-SSP method to specifically select HLA-A*0201 individuals for
      immunotherapeutic studies.
AB  - HLA-A*0201 is an important restriction element for peptide presentation to T
      cells in disease and cancer. Mutation studies and analyses using cytotoxic T
      lymphocytes have shown the functional relevance of subtype-specific differences
      in HLA-A2 molecules for peptide binding and T-cell receptor recognition.
      Therefore, many immunotherapeutic studies need to accurately select HLA-A*0201
      positive individuals. We designed an easy, robust approach based on the
      polymerase chain reaction using sequence-specific primers (PCR-SSP) to
      specifically distinguish A*0201-positive individuals from other HLA-A2 subtypes
      described to date. The first step includes reactions that give information
      whether the sample donor is HLA-A2 and, if so, whether the individual is
      homozygous or heterozygous for HLA-A2. Further, it is determined whether the
      sample has an HLA-A*0209 or an HLA-A*0201 sequence at the corresponding position
      in exon 4. Samples that may contain an HLA-A*0201 allele according to the results
      of this first step are subtyped in a second step nested PCR. Here the strategy is
      focussed on the discrimination of HLA-A*0201 from the other subtypes by
      considering divergent nucleotide positions in two ways. One SSP combination
      amplifies the HLA-A*0201 sequence while a corresponding SSP combination
      specifically amplifies the subtype or group of subtypes differing from HLA-A*0201
      at this position. Thus, at relevant polymorphic nucleotide positions the HLA
      A*0201 sequence is both directly and indirectly confirmed. This strategy strongly
      enhances the reliability of the subtyping and allows better verification of HLA
      A*0201-positive patient selection for clinical studies.

PMID- 10902610
TI  - Molecular cloning and characterization of major histocompatibility complex class
      I cDNAs from woodchuck (Marmota monax).
AB  - The full-length cDNAs of woodchuck major histocompatibility complex (MHC) class I
      (MhcMamo-I or Mamo-I) genes were cloned by using cellular mRNA isolated from the
      peripheral blood mononuclear cells and liver tissues of woodchucks. DNA sequence
      analysis of Mamo-I cDNAs revealed that the coding regions of Mamo-I genes were
      about 1,080 bp long, encoding 359 amino acid residues. The deduced amino acid
      sequences of Mamo-I showed structural features like leader, alpha1, alpha2,
      alpha3, transmembrane and cytoplasmic domains, similar to their homologues in
      human and other mammals. Analysis of five full-length clones from unrelated
      woodchucks indicated a polymorphism within the alpha1 and alpha2 domains of Mamo
      I heavy chain and a high conservation within the alpha3 and the
      transmembrane/cytoplasmic domains. Amino acid residues of the alpha2 and alpha3
      domains that are supposed to be involved in the binding of MHC class I to CD8
      molecule, were largely conserved in Mamo-I genes. Phylogenetic comparison of MHC
      class I genes of woodchuck and other mammals indicated a close evolutionary
      relationship between woodchuck and squirrel MHC class I. We tentatively named
      this region the locus A of Mamo-I genes (Mamo-A). Sequence analysis of 101 clones
      of alpha1 and alpha2 regions derived from 14 woodchucks revealed that at least 14
      different alleles within Mamo-A exist. Among these 14 alleles identified so far,
      Mamo-A*01 and Mamo-A*09 were of the highest frequency of about 21.5% and 14.5%,
      respectively. Our results indicate that Mamo-I genes are of a similar molecular
      structure to those of human and other mammals.

PMID- 10902612
TI  - Dog class I gene DLA-88 histocompatibility typing by PCR-SSCP and sequencing.
AB  - The dog has been an important model for solid organ and hematopoietic stem cell
      transplantation, as well as for studying autoimmune diseases, the growth of
      malignant tumors and the immunology of vaccines. Fundamental to the continuing
      usage of the canine model for research is the development of molecular-based
      histocompatibility typing. Previous histocompatibility methods have focused on
      class II genes. This study was undertaken to develop a molecular-based
      histocompatibility typing method for the most polymorphic class I gene, DLA-88.
      In this study, polymerase chain reaction single-stranded conformational
      polymorphism was used to separate alleles, thereby allowing sequenced-based
      typing.

PMID- 10902611
TI  - DRB3 alleles with variations in the annealing sites of commonly used
      amplification primers.
AB  - New HLA alleles are often identified initially from observing uncommon patterns
      found in low-resolution typing performed via polymerase chain reaction using
      sequence-specific oligonucleotide probes (PCR-SSOP). Recently, the HLA-DR
      oligotyping analysis of two Caucasian, one Caucasian/American Indian and two
      African American individuals resulted in the identification of three novel DRB3
      alleles. Using DRB-specific primer sets commonly employed in amplification-based
      typing, all four individuals were originally characterized as DRB3 negative.
      Direct sequencing identified DRB3*0104 (variation at codon 8, TCG instead of
      TTG), and DRB3*0101202 (variation at intron (-13), G instead of C). One
      individual appeared to carry a DR52-associated DRB1 allele without an associated
      DRB3 allele. Lack of conservation at the junction of intron 1 and exon 2 of the
      DRB3 gene suggests that commonly used DRB-specific primer sets may need to be
      modified.

PMID- 10902613
TI  - Intercellular adhesion molecule-1 (ICAM-1) K469E polymorphism: no association
      with type 1 diabetes among Finns.
AB  - The intercellular adhesion molecule-1 (ICAM-1) has an important role in the
      process of lymphocyte migration and activation, and is supposed to be involved in
      the pathogenesis of type 1 diabetes. We studied A/G (K469E) polymorphism of the
      ICAM-1 gene in 218 type 1 diabetes patients and 212 controls from Finland and
      found no association. We then studied transmission of the ICAM-1 alleles in 102
      Finnish families using a transmission disequilibrium test (TDT). Alleles A and G
      were transmitted to the affected offspring in 50% each. Stratification by the HLA
      DQB1-DQA1 genotypes, sex and age at onset did not reveal association. Our data
      demonstrate that in the Finnish population K469E polymorphism of the ICAM-1 gene
      is not associated with type 1 diabetes.

PMID- 10902614
TI  - Nomenclature for factors of the HLA system, update February 2000. WHO
      Nomenclature Committee for Factors of the HLA System.

PMID- 10902615
TI  - HIV in Latin America and the Caribbean.

PMID- 10902616
TI  - Risk of fatal pulmonary embolism with oral contraceptives.

PMID- 10902617
TI  - Strengths and weaknesses of leprosy-elimination campaigns.

PMID- 10902618
TI  - BRCA1: an emerging role in the cellular response to DNA damage.

PMID- 10902619
TI  - Towards earlier neonatal extubation.

PMID- 10902620
TI  - Effects of perinatal necropsy on counselling.

PMID- 10902621
TI  - Control of legionella in drinking-water systems.

PMID- 10902622
TI  - Extent to which low-level use of antiretroviral treatment could curb the AIDS
      epidemic in sub-Saharan Africa.
AB  - BACKGROUND: Despite growing international pressure to provide HIV-1 treatment to
      less-developed countries, potential demographic and epidemiological impacts have
      yet to be characterised. We modelled the future impact of antiretroviral use in
      South Africa from 2000 to 2005. METHODS: We produced a population projection
      model that assumed zero antiretroviral use to estimate the future demographic
      impacts of the HIV-1 epidemic. We also constructed four antiretroviral-adjusted
      scenarios to estimate the potential effect of antiretroviral use. We modelled
      total drug cost, cost per life-year gained, and the proportion of per-person
      health-care expenditure required to finance antiretroviral treatment in each
      scenario. FINDINGS: With no antiretroviral use between 2000 and 2005, there will
      be about 276,000 cumulative HIV-1-positive births, 2,302,000 cumulative new AIDS
      cases, and the life expectancy at birth will be 46.6 years by 2005. By contrast,
      110,000 HIV-1-positive births could be prevented by short-course antiretroviral
      prophylaxis, as well as a decline of up to 1 year of life expectancy. The direct
      drug costs of universal coverage for this intervention would be US$54 million-
      less than 0.001% of the per-person health-care expenditure. In comparison, triple
      combination treatment for 25% of the HIV-1-positive population could prevent a
      3.1-year decline in life expectancy and more than 430,000 incident AIDS cases.
      The drug costs of this intervention would, however, be more than $19 billion at
      present prices, and would require 12.5% of the country's per-person health-care
      expenditure. INTERPRETATION: Although there are barriers to widespread HIV-1
      treatment, limited use of antiretrovirals could have an immediate and substantial
      impact on South Africa's AIDS epidemic.

PMID- 10902623
TI  - Promotion of condom use in a high-risk setting in Nicaragua: a randomised
      controlled trial.
AB  - BACKGROUND: In Latin America, motels rent rooms for commercial and non-commercial
      sex. We investigated the impact of providing health-education material and
      condoms on condom use in Managua, Nicaragua. METHODS: In a randomised controlled
      trial, in 19 motels, we gave condoms on request, made them available in rooms, or
      gave condoms directly to couples, with and without the presence of health
      education material in the rooms. In a factorial design we assessed condom use
      directly by searching the rooms after couples had left. FINDINGS: 11 motels were
      used mainly by sex workers and their clients and eight mainly for non-commercial
      sex. 6463 couples attended the motels in 24 days. On 3106 (48.0%) occasions, at
      least one used condom was retrieved. Condom use was more frequent for commercial
      sex than for non-commercial sex (60.5 vs 20.2%). The presence of health-education
      material lowered the frequency of condom use for commercial sex (odds ratio 0.89
      [95% CI 0.84-0.94]) and had no effect on use for non-commercial sex (1.03 [0.97
      1.08]). Condom use increased for commercial (1.31 [1.09-1.75]) and non-commercial
      sex (1.81 (1.14-2.81) if condoms were available in rooms. Directly handing
      condoms to couples was similarly effective for commercial sex but less effective
      for non-commercial sex (1.32 [1.03-1.61] vs 1.52 [1.01-2.38]). INTERPRETATION: In
      Latin America, motels are key locations for promoting the use of condoms. Making
      condoms available in rooms is the most effective strategy to increase condom use,
      whereas use of health-education material was ineffective. These findings have
      important implications for HIV-prevention policies.

PMID- 10902626
TI  - Identification of a deletion in plakoglobin in arrhythmogenic right ventricular
      cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease).
AB  - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an
      autosomal dominant heart muscle disorder that causes arrhythmia, heart failure,
      and sudden death. Previously we mapped the genetic locus for the triad of
      autosomal recessive ARVC, palmoplantar keratoderma, and woolly hair (Naxos
      disease) to chromosome 17q21, in which the gene for plakoglobin is encoded. This
      protein is a key component of desmosomes and adherens junctions, and is important
      for the tight adhesion of many cell types, including those in the heart and skin.
      METHODS: We studied 19 individuals with Naxos disease, as well as unaffected
      family members and unrelated individuals from the neighbouring Greek islands of
      Naxos and Milos. Gene sequence was determined by reverse transcriptase PCR from
      RNA isolated from the skin of an affected individual and mutations in other cases
      were confirmed by restriction-enzyme analysis. FINDINGS: A homozygous 2 base pair
      deletion in the plakoglobin gene was identified only in the 19 affected
      individuals. This deletion caused a frameshift and premature termination of the
      protein, which was shown by western blot analysis. 29 clinically unaffected
      family members were heterozygous for the mutation; 20 unrelated individuals from
      Naxos and 43 autosomal dominant ARVC probands were homozygous for the normal
      allele. INTERPRETATION: The finding of a deletion in plakoglobin in ARVC suggests
      that the proteins involved in cell-cell adhesion play an important part in
      maintaining myocyte integrity, and when junctions are disrupted, cell death, and
      fibrofatty replacement occur. Therefore, the discovery of a mutation in a protein
      with functions in maintaining cell junction integrity has important implications
      for other dominant forms of ARVC, related cardiomyopathies, and other cutaneous
      diseases.

PMID- 10902624
TI  - 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults:
      double-blind, randomised and placebo controlled trial.
AB  - BACKGROUND: Infection with Streptococcus pneumoniae is a frequent and serious
      problem for HIV-immunosuppressed adults. Vaccination is recommended in the USA
      and Europe, but there are no prospective data that show vaccine efficacy.
      METHODS: 1392 (937 female) HIV-1-infected adults in Entebbe, Uganda, were
      enrolled. 697 received 23-valent pneumococcal polysaccharide vaccine and 695
      received placebo. The primary endpoint was first event invasive pneumococcal
      disease. Secondary endpoints included vaccine serogroup-specific invasive
      disease, all (probable and definite) pneumococcal events, all-cause pneumonia,
      and death. FINDINGS: First invasive events occurred in 25 individuals (24
      bacteraemias, one pyomyositis), 15 in the vaccine arm and ten in the placebo arm
      (hazard ratio [HR] 1.47; 95% CI 0.7-3.3). 22 isolates (88%) were of vaccine
      specific serogroups with 15 events in the vaccine arm compared with seven in the
      placebo arm (HR 2.10; 0.9-5.2). All pneumococcal events had a similar
      distribution (20 vs 14; HR 1.41; 0.7-2.8) though all-cause pneumonia was
      significantly more frequent in the vaccine arm (40 vs 21; HR 1.89; 1.1-3.2).
      Mortality was unaffected by vaccination. INTERPRETATION: 23-valent pneumococcal
      polysaccharide vaccination is ineffective in HIV-1-infected Ugandan adults and
      probably has little, or no, public health value elsewhere in sub-Saharan Africa.
      Increased rates of pneumococcal disease in vaccine recipients may necessitate a
      reappraisal of this intervention in other settings.

PMID- 10902625
TI  - End-of-life decisions in neonatal intensive care: physicians' self-reported
      practices in seven European countries. EURONIC Study Group.
AB  - BACKGROUND: The ethical issue of foregoing life-sustaining treatment for newborn
      infants at high risk of death or severe disability is extensively debated, but
      there is little information on how physicians in different countries actually
      confront this issue to reach end-of-life decisions. The EURONIC project aimed to
      investigate practices as reported by physicians themselves. METHODS: The study
      recruited a large, representative sample of 122 neonatal intensive-care units
      (NICUs) by census (in Luxembourg, the Netherlands, and Sweden) or stratified
      random sampling (in France, Germany, the UK, Italy, and Spain) with an overall
      response rate of 86%. Physicians' practices of end-of-life decision-making were
      investigated through an anonymous, self-administered questionnaire. 1235
      completed questionnaires were returned (response rate 89%). FINDINGS: In all
      countries, most physicians reported having been involved at least once in setting
      limits to intensive care because of incurable conditions (61-96%); smaller
      proportions reported such involvement because of a baby's poor neurological
      prognosis (46-90%). Practices such as continuation of current treatment without
      intensification and withholding of emergency manoeuvres were widespread, but
      withdrawal of mechanical ventilation was reported by variable proportions (28
      90%). Only in France (73%) and the Netherlands (47%) was the administration of
      drugs with the aim of ending life reported with substantial frequency. Age,
      length of professional experience, and the importance of religion in the
      physician's life affected the likelihood of reporting of non-treatment decisions.
      INTERPRETATION: A vast majority of neonatologists in European NICUs have been
      involved in end-of-life limitation of treatments, but type of decision-making
      varies among countries. Culture-related and other country-specific factors are
      more relevant than characteristics of individual physicians or units in
      explaining such variability.

PMID- 10902628
TI  - Unusual site of hydatid disease.

PMID- 10902627
TI  - Modulation of fluorouracil tissue pharmacokinetics by eniluracil: in-vivo imaging
      of drug action.
AB  - BACKGROUND: Fluorouracil is widely used for chemotherapy of gastrointestinal
      cancer, but response rates are poor. Eniluracil is being developed as an
      inactivator of dihydropyrimidine dehydrogenase, the enzyme that brings about
      first-pass degradation of fluorouracil. We studied the mechanism of action of
      eniluracil by measuring with positron emission tomography (PET) the effect of
      eniluracil on tumour and normal-tissue pharmacokinetics of fluorine-18-labelled
      fluorouracil. METHODS: Six patients with advanced gastrointestinal cancers were
      studied. PET scanning was done after injection of oxygen-15-labelled water to
      assess tissue blood flow, followed by 1 mg/m2 18F-fluorouracil. We compared the
      pharmacokinetics of 18F-fluorouracil when the patients had not received
      eniluracil, during a 4-day course of oral eniluracil, and during a 28-day course
      of oral fluorouracil plus eniluracil. FINDINGS: In eniluracil-naive patients, 18F
      fluorouracil localised more strongly (mean 0.0234% [SE 0.0019] of injected
      activity per mL tissue at 11 min) in liver than in tumours (0.0032% [0.0004]).
      There was substantial inhibition, after eniluracil administration, of radiotracer
      uptake and retention in normal liver (mean area under the time versus
      radioactivity curve 0.927 [SE 0.086] vs 1.857 [0.169] m2 mL(-1) s) and kidneys
      (1.096 [0.048] vs 5.043 [0.915] m2 mL(-1) s). There was also an increase in
      plasma uracil and unmetabolised 18F-fluorouracil and an increase in the
      radiotracer half-life in tumours (2.3 h to >4.0 h). INTERPRETATION: Two events
      strongly suggested increased exposure of 18F-fluorouracil and its anabolites in
      the tumours, consistent with the inactivation of dihydropyrimidine dehydrogenase:
      a selective decrease in radiotracer exposure in normal liver and kidneys compared
      with tumours; and an increase in radiotracer half-life in tumours.

PMID- 10902629
TI  - Oral contraceptives and fatal pulmonary embolism.
AB  - In a national case-control study of fatal pulmonary embolism in New Zealand women
      of childbearing age, we estimated that current users of combined oral
      contraceptives had a relative risk of 9.6 (95% CI 3.1-29.1). From national
      distribution data, the absolute risk of death from pulmonary embolism in current
      users was estimated to be 10.5 per million woman-years.

PMID- 10902630
TI  - Pharmacological implications of lengthened in-utero exposure to nevirapine.
AB  - Given as a single dose to the mother during labour, nevirapine can protect the
      neonate from HIV-1 infection for up to 7 days. However, after maternal nevirapine
      therapy during pregnancy, neonatal plasma concentrations of nevirapine decline
      more rapidly, suggesting in-utero liver enzyme induction.

PMID- 10902631
TI  - Adult cardiovascular risk factors in premature babies.
AB  - Among babies born at term, low birthweight predicts cardiovascular risk factors
      and disease in adulthood. This study shows that babies born prematurely, whether
      or not they have intrauterine growth retardation, are predisposed to similar
      risks as adults.

PMID- 10902632
TI  - Birth size and arterial compliance in young adults.
AB  - Impaired fetal growth may cause reduced compliance of the aorta and other large
      arteries, and predispose an individual to higher blood pressure in later life. We
      found that neither low birth size nor interaction between birth size and adult
      size were associated with arterial pulse-wave velocity in men and women aged 25
      years.

PMID- 10902633
TI  - Implication of HLA-G molecule in heart-graft acceptance.
AB  - HLA-G found in five of 31 heart-transplant recipients was associated with a
      decrease of acute and chronic rejection episodes.

PMID- 10902634
TI  - British Medical Journal apologises to biotech company.

PMID- 10902635
TI  - Abnormal neurokinin B concentrations may cause pre-eclampsia

PMID- 10902637
TI  - Neural transplantation: new cells for old brains.

PMID- 10902636
TI  - Canadian group reports best results yet with islet-cell transplants.

PMID- 10902638
TI  - Curtain about to raise on Labour's plan for UK health.

PMID- 10902639
TI  - More rebukes for UK gynaecologist.

PMID- 10902640
TI  - Private practice in Pakistan comes under fire.

PMID- 10902641
TI  - Canadian government urged to improve end-of-life care.

PMID- 10902642
TI  - Burden of ageing population may be greater than anticipated.

PMID- 10902643
TI  - Hit HIV-1 hard, but only when necessary.
AB  - Randomised, controlled trial data show that combination antiretroviral therapy
      for HIV-1 infection benefits people with CD4-cell counts less than 350
      cells/microL. Based on currently known risks and benefits, we believe that if CD4
      cell counts and viral load are monitored carefully, and highly active
      antiretroviral therapy (HAART) is started commonly when the CD4-cell count drops
      below 350 cells/microL, then clinically relevant immune-system damage and
      progression to AIDS and death can be greatly delayed or prevented. This approach
      is dictated by three features of HIV-1 infection that are not typical of
      infectious diseases: no available regimen can eradicate HIV-1; all currently
      effective regimens may cause undesirable, sometimes life-threatening, toxic
      effects; and, unless regimens are strictly adhered to, multidrug resistance can
      develop, limiting future treatment options. If therapy is started too early,
      cumulative side-effects of the drugs used and the development of multidrug
      resistance may outweigh the net benefits of the lengthening of life. If therapy
      is started too late, increases in disease progression and mortality outweigh the
      risk of adverse events. A patients' activist (MH) and a clinician (CCJC) discuss
      data that justify this balanced approach and the feasibility of randomised
      controlled trials to provide clearer answers about when to start treatment.

PMID- 10902644
TI  - Assessment and treatment of urinary incontinence. Scientific Committee of the
      First International Consultation on Incontinence.
AB  - The first International Consultation on Incontinence was held under the auspices
      of WHO in 1998. The multidisciplinary consultation covered anatomy, physiology,
      pathology, and the investigation and management of incontinent individuals.
      Because incontinence is a prevalent global disease, the consultation was mindful
      of the need to make its recommendations applicable in all health-care systems.
      The management recommendations are presented as nine algorithms divided into
      basic management (five) and specialised management (four), for men, women,
      children, the frail elderly, and individuals with neurogenic incontinence
      separately. The basic algorithms are intended for all health-care professionals
      working with incontinent individuals and are applied worldwide. The specialised
      algorithms are presented on The Lancet website.

PMID- 10902645
TI  - Official cigarette tar tests are misleading: use a two-stage, compensating test.

PMID- 10902646
TI  - The debate on HIV in Africa.

PMID- 10902647
TI  - The debate on HIV in Africa.

PMID- 10902648
TI  - The debate on HIV in Africa.

PMID- 10902649
TI  - The debate on HIV in Africa.

PMID- 10902650
TI  - Dengue versus hantavirus in CNS infections.

PMID- 10902651
TI  - Colitis and docetaxel-based chemotherapy.

PMID- 10902652
TI  - Neuroleptic malignant syndrome after venlafaxine.

PMID- 10902653
TI  - Insulin for the world's poorest countries.

PMID- 10902654
TI  - Insulin for the world's poorest countries.

PMID- 10902655
TI  - Insulin for the world's poorest countries.

PMID- 10902656
TI  - Insulin for the world's poorest countries.

PMID- 10902657
TI  - Insulin for the world's poorest countries.

PMID- 10902658
TI  - Community views on health programmes in Uganda.

PMID- 10902659
TI  - Charles Bonnet syndrome and dementia.

PMID- 10902660
TI  - Reducing withdrawal bleeds.

PMID- 10902662
TI  - Recognising letters in systematic reviews.

PMID- 10902661
TI  - Marital status and maternal mortality.

PMID- 10902663
TI  - A vote for open refereeing.

PMID- 10902664
TI  - That smile.

PMID- 10902665
TI  - Injury risks among chimpanzees in three housing conditions.
AB  - Meeting the psychological needs of chimpanzees (Pan troglodytes) can be a
      challenge given their aggressiveness on the one hand and the complexity of their
      social lives on the other. It is unclear how to balance the need to provide
      opportunities for species-appropriate behavior against potential risks of injury
      chimpanzees may inflict on each other. This study evaluates the suggestion that
      simpler social environments protect chimpanzees from wounding. Over a two-year
      period all visible injuries to 46 adult males, 64 adult females, and 25 immature
      chimpanzees were recorded at the Yerkes Regional Primate Research Center.
      Approximately half of the subjects were mother-reared, and the rest were nursery
      reared. Housing included compounds containing about 20 chimpanzees,
      interconnected indoor-outdoor runs for groups of up to 12 individuals, and
      smaller indoor-outdoor runs for pairs and trios. Annual wounding rates were
      calculated for serious wounds (extensive injuries and all those requiring
      veterinary intervention) as well as for minor wounds. Compound-housed chimpanzees
      incurred the highest level of minor wounding, but serious wounding levels were
      not affected by housing condition. Even with a period of dominance instability
      and elevated levels of wounding in one compound, compound chimpanzees were not
      injured more than those in smaller social groups over the long term. Nursery
      reared females in moderate-sized groups were wounded more than mother-reared
      females. Also, nursery-reared males and females were wounded less often when
      paired with mother-reared companions. Overall, this study indicates that
      maintaining chimpanzees in pairs and trios would not be an effective means for
      reducing injuries. The management of wounding in chimpanzee colonies is
      influenced more by the sex and rearing composition of a colony.

PMID- 10902666
TI  - Grooming, social bonding, and agonistic aiding in rhesus monkeys.
AB  - An analysis of simultaneous grooming bouts in a captive group of rhesus monkeys
      (Macaca mulatta) failed to provide evidence of competition to groom high ranking
      partners. Not only were grooming supplantations rare, but the highest ranking
      individuals performing grooming did not groom the highest ranking animals
      receiving grooming. Lower ranking partners, however, did more grooming in nonkin
      dyads. Grooming partners aided one another in agonistic episodes, but the
      individual receiving the aid did not groom the individual providing the aid more
      than vice versa. Kin dyads did aid and groom one another at greater than expected
      rates, but the aider did not receive the greater proportion of grooming in the
      dyad. Males participated in more grooming than expected, but their grooming was
      not related to aiding either with regard to one another or female partners.
      Animals that were targeted in joint aggression, or aided against, received
      significantly less grooming from their opponents. A general social relationship
      expressed in partner preferences, social grooming, and agonistic aiding better
      explained the observed pattern than any model based on the exchange of services
      for favors in different currencies.

PMID- 10902667
TI  - Measurement of scrotum and testis size of unrestrained captive cotton-top
      tamarins (Saguinus oedipus oedipus).
AB  - Reproduction is restricted to a small number of animals within both captive and
      wild groups of callitrichid monkeys (marmosets and tamarins). Sexual development
      of nonbreeding group members might differ from that of active breeders.
      Measurements of physical growth typically involve animal handling. However,
      capture and restraint of callitrichid monkeys can disrupt natural behaviors and
      physiology. This study introduces a method for estimating size of external
      genitalia by measuring frontal scrotum width of unrestrained cotton-top tamarin
      males. We examined whether scrotum width was a reliable indicator of testis size,
      and whether the method provided information useful for comparisons of growth and
      development among individuals. Animals were lured to a standardized position, and
      maximum width of the scrotum was systematically compared to a card with a series
      of rectangles graded in 1 mm increments. Card measures were validated with
      caliper measurements of scrotum width and testicle dimensions. Regressions of
      testes dimensions measured by caliper on scrotum width measured by card were
      between 82 and 93%, suggesting that measures of frontal scrotum width provide
      consistent estimates of relative testis sizes. The period of rapid growth ended
      by roughly two years of age, after which scrotum size did not differ from that of
      breeding males.

PMID- 10902668
TI  - Relationship between chimpanzee (Pan troglodytes) density and large, fleshy-fruit
      tree density: conservation implications.
AB  - Conservation efforts to protect chimpanzees in their natural habitat are of the
      highest priority. Unfortunately, chimpanzee density is notoriously difficult to
      determine, making it difficult to assess potential chimpanzee conservation areas.
      The objective of this study was to determine whether chimpanzee density could be
      predicted from the density of trees that produce large, fleshy fruits. Using
      chimpanzee nest counts from six sites within Kibale National Park, Uganda,
      collected during a year-long study, a predictive trend was found between
      chimpanzee nest density and large, fleshy-fruit tree density. This relationship
      may offer a quick, reasonably reliable method of estimating potential chimpanzee
      densities in previously unsurveyed habitats and may be used to evaluate the
      suitability of possible re-introduction sites. Thus, in conjunction with other
      survey techniques, such as forest reconnaissance, it may provide an effective and
      efficient means of determining appropriate chimpanzee habitat in which to
      allocate conservation efforts.

PMID- 10902669
TI  - Fur rubbing behavior in free-ranging black-handed spider monkeys (Ateles
      geoffroyi) in Panama.
AB  - Members of the population of black-handed spider monkeys (Ateles geoffroyi) on
      Barro Colorado Island, Panama, use the leaves of three Rutaceae species in a
      behavior that resembles fur rubbing in the white faced capuchin (Cebus
      capucinus). This behavior has not been reported from other sites where Ateles has
      been studied. During more than 1,200 hours of observation, 30 episodes of this
      behavior were recorded ad libitum. Adult males engage in this behavior more than
      adult females. Season did not impact the frequency of the behavior. The behavior
      described here differs in many respects from that reported for Cebus capucinus,
      and does not fit the hypotheses that the behavior functions in repelling insects
      or other antiseptic purposes. It is proposed that fur rubbing in this group of
      spider monkeys is a modification of a behavior previously recorded in Ateles and
      may function in scent marking.

PMID- 10902671
TI  - Mediating and moderating variables: a conceptual clarification.

PMID- 10902670
TI  - Reproductive monitoring of free-ranging female mountain gorillas by urinary
      hormone analysis.
AB  - Frequent urine samples from three habituated free-ranging adult female mountain
      gorillas were collected during a four-week period in order to characterize, by
      analysis of urinary hormones, their ovarian cycle, and to diagnose pregnancy. A
      conceptive cycle and two cycles that did not result in full term pregnancy were
      monitored. Behavioral and physiological observations of mating and labial
      swellings were correlated to urinary hormone results. Mating occurred on days
      with elevated estrogens. Labial swelling was maximum near or at peak estrogen
      levels. Pregnancy was diagnosed at the field site by measurement of chorionic
      gonadotropin using commercially available human pregnancy detection kits. In one
      pregnancy, gestation length was 254 days. The pregnanediol glucuronide
      concentrations of the mountain gorilla did not change during the nonconceptive
      cycle. During the conceptive cycle, the concentrations did not increase until the
      approximate time of implantation. This finding suggests marked differences in
      steroid production or metabolism between the mountain gorilla and the captive
      lowland gorilla.

PMID- 10902672
TI  - The regulation of release parameters in underarm precision throwing.
AB  - The aim of this study was to determine if adults spontaneously exploit the laws
      of physics to achieve better accuracy when throwing at various distances. Eight
      adults performed 25 underarm throws at five horizontal circular targets located
      4, 5, 6, 7 and 8 m away with a constant 5% relative accuracy requirement. Angle
      and speed of the ball at release were found to increase with throwing distance,
      while the coordinates of the release point did not change significantly. These
      results support the idea that people minimize the variability in impact distance
      by adapting both the angle and the speed at ball release following a mechanical
      optimum predicted by the laws of physics. Moreover, variability in distance was
      found to be less than expected because of independent variations in the angle and
      speed at ball release. Hence, the control of precision throwing seems to imply
      compensatory variability, as frequently reported in the control of skilled
      actions.

PMID- 10902673
TI  - Children's physical activity and physical self-perceptions.
AB  - The aim of this study was to determine the relationship between physical self
      perceptions and physical activity in Canadian school children aged 10-14 years.
      The sample consisted of 220 boys and 246 girls in grades 5-8. Physical activity
      was assessed by 7-day recall using the Physical Activity Questionnaire for Older
      Children. Self-perceptions of physical conditioning, sports competence, strength,
      body appearance and general physical self-worth were measured by the Physical
      Self-Perception Profile (PSPP). We found that boys were more physically active
      than girls and had higher perceptions of sport competence and strength. All PSPP
      scales were significantly correlated with physical activity in both boys and
      girls. Structural equation modelling procedures found the hierarchical PSPP model
      provided a good fit to the observed data, with little evidence of differences
      between the sexes. Analysis of five alternative structural models of the
      relationship between the PSPP and physical activity found the most parsimonious
      model to have significant pathways from both physical conditioning and sport
      skills to physical activity. Models for the sample as a whole, for boys and for
      girls were similar, accounting for an R2 of 0.27-0.29 for physical activity. Our
      results demonstrate that physical self-perceptions, especially physical
      conditioning and sport skills, are significant correlates of activity in this
      population.

PMID- 10902674
TI  - Kinanthropometric and physiological characteristics of outrigger canoe paddlers.
AB  - We describe the physiological characteristics of amateur outrigger canoe
      paddlers. Twenty-one paddlers (13 males, 8 females) were evaluated for body
      stature, aerobic power, muscular strength and endurance, peak paddle force,
      flexibility and 250 m sprint paddle performance at the end of the outrigging
      season. The mean variables (+/- s) for the males were: age 27 +/- 9 years, height
      175 +/- 5 cm, body mass 80 +/- 5 kg, arm span 178 +/- 7 cm, sitting height 100 +/
      2 cm, aerobic power 3.0 +/- 0.4 l x min(-1), maximum bench press strength 85 +/-
      19 kg, right peak paddle force 382 +/- 66 N and left peak paddle force 369 +/- 69
      N. For the females, these were: age 26 +/- 6 years, height 168 +/- 5 cm, body
      mass 70 +/- 8 kg, arm span 170 +/- 5 cm, sitting height 97 +/- 3 cm, aerobic
      power 2.3 +/- 0.51 l x min(-1), maximum bench press strength 47 +/- 10 kg, right
      peak paddle force 252 +/- 63 N and left peak paddle force 257 +/- 60 N. Analysis
      of variance revealed differences (P < 0.05) between the dominant and non-dominant
      sides of the body for peak paddle force, isokinetic internal and external
      rotation, and flexion and extension torque of the shoulder joint. The outrigger
      canoe paddlers were generally within the range of scores found to describe
      participants of other water craft sports. Outrigger canoeists should be concerned
      with the muscular strength imbalances associated with paddling technique.

PMID- 10902675
TI  - On winning the penalty shoot-out in soccer.
AB  - The penalty shoot-out is used to break tied games in the knock-out stages of
      soccer competition. The shoot-out, which consists of an alternating series of
      penalty kicks, is won by the team with the highest goal tally after n kicks per
      team (n = 5). In the event of a tie after five penalty kicks each, the shoot-out
      progresses to 'sudden death' by increasing n in iterative fashion (i.e. n = n +
      1) until one team obtains a higher goal tally than the other after an equal
      number of kicks per team. The team to strike first is determined at the end of
      extra time by the toss of a coin. As each on-field player can be awarded only a
      single penalty kick, the line-up order in which the penalty kicks are taken
      allows for the possibility of tactical influence on the final outcome.
      Consequently, we report a probability analysis of the penalty shoot-out in soccer
      from which we identify the following pre- and post-game strategies. The best five
      ranked penalty takers from the on-field players should be assigned to the first
      five penalty kicks in their reverse order of ability. That is, the fifth best
      penalty taker should take the first penalty kick, the fourth best penalty taker
      should take the second penalty kick, and so on. In the event of sudden death, the
      next highest ranked on-field player should be assigned to the next penalty kick
      until the shoot-out ends. For this tactic to be successful, players should be
      ranked a priori on their penalty-taking ability. Similarly, goalkeepers should be
      ranked a priori on their penalty-stopping ability. These findings indicate that
      the tactical substitution of on-field players for higher ranked penalty takers,
      including higher ranked penalty stoppers (i.e. goalkeepers), with a view to an
      impending penalty shoot-out should be given due consideration. These results are
      of practical importance in that they are shown to maximize the likelihood of
      winning the penalty shoot-out under certain initial conditions.

PMID- 10902676
TI  - Acclimatization to altitude and normoxic training improve 400-m running
      performance at sea level.
AB  - To investigate the benefits of 'living high and training low' on anaerobic
      performance at sea level, eight 400-m runners lived for 10 days in normobaric
      hypoxia in an altitude house (oxygen content = 15.8%) and trained outdoors in
      ambient normoxia at sea level. A maximal anaerobic running test and 400-m race
      were performed before and within 1 week of living in the altitude house to
      determine the maximum speed and the speeds at different submaximal blood lactate
      concentrations (3, 5, 7, 10 and 13 mmol x l(-1)) and 400-m race time. At the same
      time, ten 400-m runners lived and trained at sea level and were subjected to
      identical test procedures. Multivariate analysis of variance indicated that the
      altitude house group but not the sea-level group improved their 400-m race time
      during the experimental period (P < 0.05). The speeds at blood lactate
      concentrations of 5-13 mmol x l(-1) tended to increase in the altitude house
      group but the response was significant only at 5 and 7 mmol x l(-1) (P < 0.05).
      Furthermore, resting blood pH was increased in six of the eight altitude house
      athletes from 0.003 to 0.067 pH unit (P < 0.05). The results of this study
      demonstrate improved 400-m performance after 10 days of living in normobaric
      hypoxia and training at sea level. Furthermore, the present study provides
      evidence that changes in the acid-base balance and lactate metabolism might be
      responsible for the improvement in sprint performance.

PMID- 10902677
TI  - An analysis of selected kinematic variables in national and elite male and female
      100-m and 200-m breaststroke swimmers.
AB  - The kinematic analysis of competition breaststroke swimming has tended to focus
      on the mean values of swimming speed, stroke rate and stroke length; values in
      individual lengths, as well as the start, turns and finish, have largely been
      ignored. This study includes all such variables and aims to improve the coach's
      holistic understanding of breaststroke racing by determining the relationships
      and differences between and within these selected kinematic variables. We also
      compare 100-m events with 200-m events to determine if there are characteristic
      differences between them. Competitive breaststroke swimming performances in 100-m
      events (males: n = 159, finishing time = 65.05 +/- 2.62 s; females: n = 158,
      finishing time = 74.04 +/- 3.66 s) and 200-m events (males: n = 159, finishing
      time = 141.47 +/- 6.15 s; females: n = 158, finishing time = 158.66 +/- 7.87 s)
      were collected and analysed from 12 world, international and national
      championships. The better 100-m and 200-m breaststroke swimmers were found to
      demonstrate greater competency in the kinematic variables measured, except stroke
      kinematics, which were unique to each individual. These findings suggest that
      coaches should place emphasis on all of the kinematic components in training and
      that they should attempt to identify the stroke rate to stroke length ratio most
      appropriate for the individual. Finally, characteristic differences do exist
      between the 100-m and 200-m events, which has implications for how swimmers might
      train for each event.

PMID- 10902678
TI  - Theory and practice in sport psychology and motor behaviour needs to be
      constrained by integrative modelling of brain and behaviour.
AB  - Because of advances in technology, the non-invasive study of the human brain has
      enhanced the knowledge base within the neurosciences, resulting in an increased
      impact on the psychological study of human behaviour. We argue that application
      of this knowledge base should be considered in theoretical modelling within sport
      psychology and motor behaviour alongside existing ideas. We propose that
      interventions founded on current theoretical and empirical understanding in both
      psychology and the neurosciences may ultimately lead to greater benefits for
      athletes during practice and performance. As vehicles for exploring the arguments
      of a greater integration of psychology and neurosciences research, imagery and
      perception-action within the sport psychology and motor behaviour domains will
      serve as exemplars. Current neuroscience evidence will be discussed in relation
      to theoretical developments; the implications for sport scientists will be
      considered.

PMID- 10902679
TI  - Development of a boxing dynamometer and its punch force discrimination efficacy.
AB  - The development of sport-specific dynamometers is an important step towards
      ecological validity in analysing athlete performance. Design limitations in
      previous punch-measuring devices have resulted in values which may not or cannot
      fully reflect the force and multidirectional components in a punch. In developing
      this boxing dynamometer, a triaxial force measurement system and a boxing manikin
      interface were combined. The repeatability and accuracy of the dynamomoter were
      assessed using simulated straight punches. Discrimination efficacy was assessed
      by comparison of the maximal punching force of seven elite, eight intermediate
      and eight novice boxers during simulated boxing, throwing straight punches. For
      the elite, intermediate and novice groups, respectively, the maximal straight
      punching forces (mean +/- s(mean)) were 4800 +/- 227 N, 3722 +/- 133 N and 2381
      +/- 116 N for the rear hand, and 2847 +/- 225 N, 2283 +/- 126 N and 1604 +/- 97 N
      for the lead hand. For all groups, maximal forces were larger for the rear than
      the lead hand (P < 0.001). Maximal punching force was greater in the elite than
      the intermediate group, and greater in the intermediate than the novice group (P
      < 0.05). The boxing dynamometer discriminated effectively between punching
      performance at three standards of performance and between the punching force of
      the rear and lead hands.

PMID- 10902680
TI  - The impact of individual efficacy beliefs on group goal selection and group goal
      commitment.
AB  - Collective efficacy research has begun to progress from simply trying to verify
      the relationship between collective efficacy and performance to examining the
      mechanisms through which collective efficacy impacts on performance. To test
      hypotheses concerning the impact of collective efficacy on group goal selection
      and commitment, 24 participants were assigned to triads (consisting of the
      participant and two confederates) and performed two time-trials on cycle
      ergometers. Before each trial, the participants were asked to select both a
      finishing time and position goal for their group and to indicate their commitment
      towards these goals. After trial 1, the participants were assigned to either a
      high or low collective efficacy condition and received appropriate bogus
      performance feedback. Analysis of variance and post-hoc tests revealed that
      participants in the low collective efficacy group significantly reduced both
      finishing time and group position goals from trial 1 to trial 2, whereas
      participants in the high collective efficacy group maintained their goals. These
      results provide support for Bandura's suggestions concerning the mechanisms
      through which collective efficacy impacts upon performance.

PMID- 10902681
TI  - Water-borne sperm trigger vitellogenic egg growth in two sessile marine
      invertebrates.
AB  - A diverse array of sessile marine invertebrates mate by passive dispersal of
      sperm which fertilize the brooded eggs of neighbours. In two such species, a sea
      mat (phylum Bryozoa) and an ascidian (phylum Chordata), vitellogenic egg growth
      is absent in reproductively isolated specimens, but is triggered by a water-borne
      factor released by conspecifics. In both of these colonial, hermaphroditic
      species, the active factor can be removed from water by filtration. The effect
      involves self-/non-self-recognition: water conditioned by a separate subcolony of
      the same genetic individual does not prompt oocyte growth. In each species,
      allosperm move from the surrounding water to the ovary and are then stored in
      close association with the growing oocytes. We concluded that sperm themselves
      are the water-borne factor that triggers the major phase of female reproductive
      investment. This mechanism is, to our knowledge, previously undescribed in
      animals, but has parallels with the initiation of maternal investment in
      flowering plants following the receipt of compatible pollen. The species studied
      may be representative of many other aquatic invertebrates which mate in a similar
      way. The stimulation of egg growth by allosperm could lead to intersexual
      conflict during oogenesis.

PMID- 10902682
TI  - Male calling song provides a reliable signal of immune function in a cricket.
AB  - A critical prediction of the immunocompetence handicap hypothesis is that the
      expression of secondary sexual traits should be positively correlated with
      pathogen resistance ability This correlation is necessary if females are to be
      able to use a particular sexual trait as an indicator of a male's resistance
      ability. In this study we document a positive correlation between a sexually
      selected component of the calling song of male house crickets (the number of
      syllables per chirp) and haemocyte load, an important determinant of the ability
      to encapsulate pathogens in insects. The results indicate that, by favouring
      males which produce more syllables per chirp, females may also select males with
      higher pathogen resistance ability, potentially generating either direct or
      indirect selection on female mating preferences.

PMID- 10902683
TI  - Host-plant diversity of the European corn borer Ostrinia nubilalis: what value
      for sustainable transgenic insecticidal Bt maize?
AB  - The strategies proposed for delaying the development of resistance to the
      Bacillus thuringiensis toxins produced by transgenic maize require high levels of
      gene flow between individuals feeding on transgenic and refuge plants. The
      European corn borer Ostrinia nubilalis (Hubner) may be found on several host
      plants, which may act as natural refuges. The genetic variability of samples
      collected on sagebrush (Artemisia sp.), hop (Humulus lupulus L.) and maize (Zea
      mays L.) was studied by comparing the allozyme frequencies for six polymorphic
      loci. We found a high level of gene flow within and between samples collected on
      the same host plant. The level of gene flow between the sagebrush and hop insect
      samples appeared to be sufficiently high for these populations to be considered a
      single genetic panmictic unit. Conversely, the samples collected on maize were
      genetically different from those collected on sagebrush and hop. Three of the six
      loci considered displayed greater between-host-plant than within-host-plant
      differentiation in comparisons of the group of samples collected on sagebrush or
      hop with the group of samples collected on maize. This indicates that either
      there is genetic isolation of the insects feeding on maize or that there is host
      plant divergent selection at these three loci or at linked loci. These results
      have important implications for the potential sustainability of transgenic
      insecticidal maize.

PMID- 10902684
TI  - Soldier morphogenesis in a nasute termite: discovery of a disc-like structure
      forming a soldier nasus.
AB  - Nasute termites belonging to the subfamily Nasutitermitinae, have a soldier caste
      that possesses a frontal projection (nasus) on the head, from which defensive
      substances are secreted. In the course of caste differentiation of the
      processional nasute termite Hospitalitermes medioflavus, the most dynamic
      morphogenesis occurs in the stage of moulting from male minor worker to
      presoldier (the stage preceding the soldier stage). We examined the presumptive
      nasus epithelium in minor workers and determined that the nasus develops rapidly
      just prior to the moulting to presoldiers. The rapid growth is associated with
      two folding layers of cuticle and epithelium, which we termed the soldier-nasus
      disc, and resembles the imaginal discs found in holometabolous insects.

PMID- 10902685
TI  - Predicted decline of protected whales based on molecular genetic monitoring of
      Japanese and Korean markets.
AB  - We present a two-tiered analysis of molecular genetic variation in order to
      determine the origins of whale' products purchased from retail markets in Japan
      and the Republic of (South) Korea during 1993-1999. This approach combined
      phylogenetic analysis of mitochondrial DNA sequences for identification of
      protected species with a statistical comparison of intraspecific haplotype
      frequencies for distinguishing regional subpopulations or 'stocks' hunted for
      scientific research by the Japanese and killed incidentally in coastal fisheries
      by the Koreans. The phylogenetic identification of 655 products included eight
      species or subspecies of baleen whales, sperm whales, a pygmy sperm whale, two
      species of beaked whales, porpoises, killer whales and numerous species of
      dolphins as well as domestic sheep and horses. Six of the baleen whale species
      (the fin, sei, common-form and small-form Bryde's, blue or blue/fin hybrid, and
      humpback) and the sperm whale are protected by international agreements dating
      back to at least 1989 for all species and 1966 for some species. We compared the
      haplotype frequencies from the Japanese market sample to those reported from
      scientific hunting in the western North Pacific stock for products derived from
      the exploited North Pacific minke whale. The market sample differed significantly
      from the scientific catch (p < 0.001), showing a greater than expected frequency
      of haplotypes characteristic of the protected Sea of Japan stock. We used a
      'mixed-stock' analysis and maximum-likelihood methods to estimate that 31% (95%
      confidence interval 19-43%) of the market for this species originated from the
      Sea of Japan stock. The source of these products was assumed to be undocumented
      'incidental takes' from fisheries' by-catch, although we cannot exclude the
      possibility of illegal hunting or smuggling. The demographic impact of this
      undocumented exploitation was evaluated using the model of population dynamics
      adopted by the Scientific Committee of the International Whaling Commission. For
      the range of exploitation consistent with the market sample, this protected stock
      was predicted to decline towards extinction over the next few decades. These
      results confirmed the power of molecular methods in monitoring retail markets and
      pointed to the inadequacy of the current moratorium for ensuring the recovery of
      protected species. More importantly, the integration of genetic evidence with a
      model of population dynamics identified an urgent need for actions to limit
      undocumented exploitation of a 'protected' stock of whales.

PMID- 10902686
TI  - Phylogenetic relationships among the Nymphalidae (Lepidoptera) inferred from
      partial sequences of the wingless gene.
AB  - A cladistic analysis was performed on a 378 bp region of the wingless gene from
      103 nymphalid species and three pierid outgroups in order to infer higher level
      patterns of relationship among nymphalid subfamilies and tribes. Although the
      data are highly homoplastic, in many instances the most parsimonious cladograms
      corroborate traditionally recognized groups. The results suggest that this short
      gene region provides a useful source of data for phylogenetic inference, provided
      that adequate effort is made to sample a diversity of taxa.

PMID- 10902688
TI  - Developments of the Price equation and natural selection under uncertainty.
AB  - Many approaches to the study of adaptation, following Darwin, centre on the
      number of offspring of individuals. Population genetics theory makes clear that
      predicting gene frequency changes requires more detailed knowledge, for example
      of linkage and linkage disequilibrium and mating systems. Because gene frequency
      changes underlie adaptation, this can lead to a suspicion that approaches
      ignoring these sophistications are approximate or tentative or wrong. Stochastic
      environments and sexual selection are two topics in which there are widespread
      views that focusing on number of offspring of individuals is not enough, and that
      proper treatments require the introduction of further details, namely variability
      in offspring number and linkage disequilibrium, respectively. However, the bulk
      of empirical research on adaptation and a great deal of theoretical work continue
      to employ these approaches. Here, a new theoretical development arising from the
      Price equation provides a formal justification in very general circumstances for
      focusing on the arithmetic average of the relative number of offspring of
      individuals.

PMID- 10902689
TI  - Ultrastructure of the post-corpus of Zeldia punctata (Cephalobina) for analysis
      of the evolutionary framework of nematodes related to Caenorhabditis elegans
      (Rhabditina).
AB  - The ultrastructure of the post-corpus of Zeldia punctata (Cephalobina) was
      compared with previous observations of Caenorhabditis elegans (Rhabditina) and
      Diplenteron sp. (Diplogastrina) with the goal of interpreting the morphological
      evolution of the feeding structures in the Secernentea. The post-corpus of Z.
      punctata consists of six marginal, 13 muscle, five gland and seven nerve cells.
      The most anterior of four layers of muscle cells consists of six mononucleate
      cells in Z. punctata. The homologous layer in C. elegans and Diplenteron consists
      of three binucleate cells, suggesting a unique derived character (synapomorphy)
      shared between the Rhabditina and Diplogastrina. Contrary to Diplenteron sp.
      where we observed three oesophageal glands, Z. punctata and C. elegans have five
      oesophageal glands. We question this shared character as reflecting a common
      evolution between the Cephalobina and Rhabditina, because there are strong
      arguments for functional (adaptive) convergence of the five glands in these
      bacterial feeders. Convergence is further suggested by the mosaic distribution of
      three versus five glands throughout the Nemata; this distribution creates
      difficulties in establishing character polarity. Although morphological data are
      often laborious to recover and interpret, we nevertheless view 'reciprocal
      illumination' between molecular and morphological characters as the most
      promising and robust process for reconstructing the evolution of the Secernentea
      and its feeding structures.

PMID- 10902687
TI  - Early-branching or fast-evolving eukaryotes? An answer based on slowly evolving
      positions.
AB  - The current paradigm of eukaryotic evolution is based primarily on comparative
      analysis of ribosomal RNA sequences. It shows several early-emerging lineages,
      mostly amitochondriate, which might be living relics of a progressive assembly of
      the eukaryotic cell. However, the analysis of slow-evolving positions, carried
      out with the newly developed slow-fast method, reveals that these lineages are,
      in terms of nucleotide substitution, fast-evolving ones, misplaced at the base of
      the tree by a long branch attraction artefact. Since the fast-evolving groups are
      not always the same, depending on which macromolecule is used as a marker, this
      explains most of the observed incongruent phylogenies. The current paradigm of
      eukaryotic evolution thus has to be seriously re-examined as the eukaryotic
      phylogeny is presently best summarized by a multifurcation. This is consistent
      with the Big Bang hypothesis that all extant eukaryotic lineages are the result
      of multiple cladogeneses within a relatively brief period, although insufficiency
      of data is also a possible explanation for the lack of resolution. For further
      resolution, rare evolutionary events such as shared insertions and/or deletions
      or gene fusions might be helpful.

PMID- 10902690
TI  - Biological microtribology: anisotropy in frictional forces of orthopteran
      attachment pads reflects the ultrastructure of a highly deformable material.
AB  - Evolutionarily optimized frictional devices of insects are usually adapted to
      attach to a variety of natural surfaces. Orthopteran attachment pads are composed
      of hexagonal outgrowths with smooth flexible surfaces. The pads are designed to
      balance the weight of the insect in different positions and on different
      materials. In a scanning electron microscopy study followed by freezing
      substitution experiments, the ultrastructural architecture of the pad material
      was visualized. In friction experiments, the interaction was measured between the
      attachment pad and a polished silicon surface. The inner structure of this
      material contains distally directed rods, branching close to the surface, and
      spaces filled with fluid. The specific design of the pad material provides a
      higher frictional force in the distal direction. Frictional anisotropy is more
      enhanced at higher normal forces and lower sliding velocities. It is concluded
      that optimal mechanical functionality of biosystems is the result of a
      combination of surface structuring and material design.

PMID- 10902691
TI  - Metabolic compensation during high energy output in fasting, lactating grey seals
      (Halichoerus grypus): metabolic ceilings revisited.
AB  - Lactation is the most energetically expensive period for female mammals and is
      associated with some of the highest sustained metabolic rates (SusMR) in
      vertebrates (reported as total energy throughput). Females typically deal with
      this energy demand by increasing food intake and the structure of the alimentary
      tract may act as the central constraint to ceilings on SusMR at about seven times
      resting or standard metabolic rate (SMR). However, demands of lactation may also
      be met by using a form of metabolic compensation such as reducing locomotor
      activities or entering torpor. In some phocid seals, cetaceans and bears, females
      fast throughout lactation and thus cannot offset the high energetic costs of
      lactation through increased food intake. We demonstrate that fasting grey seal
      females sustain, for several weeks, one of the highest total daily energy
      expenditures (DEE; 7.4 x SMR) reported in mammals, while progressively reducing
      maintenance metabolic expenditures during lactation through means not explained
      by reduction in lean body mass or behavioural changes. Simultaneously, the energy
      exported in milk is progressively increased, associated with increased
      lipoprotein lipase activity in the mammary gland, resulting in greater offspring
      growth. Our results suggest that females use compensatory mechanisms to help meet
      the extraordinary energetic costs of lactation. Additionally, although the
      concepts of SusMR and ceilings on total DEE may be somewhat different in fasting
      lactating species, our data on phocid seals demonstrate that metabolic ceilings
      on milk energy output, in general, are not constrained by the same kind of
      peripheral limitations as are other energy-consuming tissues. In phocid seals,
      the high ceilings on DEE during lactation, coupled with metabolic compensation,
      are undoubtedly important factors enabling shortened lactation.

PMID- 10902693
TI  - The relationship between serial monogamy and rape in the United States (1960
      1995).
AB  - In mating systems where individuals pair, separate and re-pair repeatedly (i.e.
      serial monogamy), some males monopolize more than one female's reproductive life
      span and thus leave other males effectively mateless. Males who cannot secure
      females through traditional methods may seek alternatives, such as rape, to
      ensure gene passage into future generations. Analysis of US government records
      shows that (i) divorce and remarriage patterns in the United States are likely to
      increase the variance in male reproductive success, and (ii) rates of divorce and
      rape correlate positively. The former result suggests that serial monogamy
      increases the variance in male, relative to female, reproductive success and the
      latter result suggests that this variance influences the frequency of rape in
      American society. Because raped females sometimes become pregnant and take these
      pregnancies to term, our results indicate that rape has current adaptive
      significance.

PMID- 10902692
TI  - Category differences in brain activation studies: where do they come from?
AB  - Differences in the neural processing of six categories of pictorial stimuli
      (maps, body parts, objects, animals, famous faces and colours) were investigated
      using positron emission tomography. Stimuli were presented either with or without
      the written name of the picture, thereby creating a naming condition and a
      reading condition. As predicted, naming increased the demands on lexical
      processes. This was demonstrated by activation of the left temporal lobe in a
      posterior region associated with name retrieval in several previous studies. This
      lexical effect was common to all meaningful stimuli and no category-specific
      effects were observed for naming relative to reading. Nevertheless, category
      differences were found when naming and reading were considered together. Stimuli
      with greater visual complexity (animals, faces and maps) enhanced activation in
      the left extrastriate cortex. Furthermore, map recognition, which requires
      greater spatio-topographical processing, also activated the right occipito
      parietal and parahippocampal cortices. These effects in the visuo-spatial regions
      emphasize inevitable differences in the perceptual properties of pictorial
      stimuli. In the semantic temporal regions, famous faces and objects enhanced
      activation in the left antero-lateral and postero-lateral cortices, respectively.
      In addition, we showed that the same posterior left temporal region is also
      activated by body parts. We conclude that category-specific brain activations
      depend more on differential processing at the perceptual and semantic levels
      rather than at the lexical retrieval level.

PMID- 10902694
TI  - Imaginary companions of preschool children.
AB  - The developmental significance of preschool children's imaginary companions was
      examined. Mothers of 78 children were interviewed about their children's social
      environments and imaginary companions (if their children had them). Results
      revealed differences between invisible companions and personified objects (e.g.,
      stuffed animals or dolls) in terms of the pretend friends' stability and
      ubiquity, identity, and relationship with the child. Relationships with invisible
      companions were mostly described as sociable and friendly, whereas personified
      objects were usually nurtured. Mothers reported that personification of objects
      frequently occurred as a result of acquiring a toy, whereas invisible friends
      were often viewed as fulfilling a need for a relationship. Compared to children
      without imaginary companions, children with imaginary companions were more likely
      to be firstborn and only children.

PMID- 10902695
TI  - Are associations between parental divorce and children's adjustment genetically
      mediated? An adoption study.
AB  - The hypothesis that the association between parental divorce and children's
      adjustment is mediated by genetic factors was examined in the Colorado Adoption
      Project, a prospective longitudinal study of 398 adoptive and biological
      families. In biological families, children who experienced their parents'
      separation by the age of 12 years exhibited higher rates of behavioral problems
      and substance use, and lower levels of achievement and social adjustment,
      compared with children whose parents' marriages remained intact. Similarly,
      adopted children who experienced their (adoptive) parents' divorces exhibited
      elevated levels of behavioral problems and substance use compared with adoptees
      whose parents did not separate, but there were no differences on achievement and
      social competence. The findings for psychopathology are consistent with an
      environmentally mediated explanation for the association between parent divorce
      and children's adjustment; in contrast, the findings for achievement and social
      adjustment are consistent with a genetically mediated explanation involving
      passive genotype-environment correlation.

PMID- 10902696
TI  - Affective predictors of preschoolers' aggression and peer acceptance: direct and
      indirect effects.
AB  - Observational assessments were made of 51 preschoolers' (mean age = 53.25 months)
      peer aggression and emotional displays outside of (baseline) and during
      aggressive interactions, and their emotion knowledge and peer acceptance were
      also assessed. Results indicated that the connections between children's
      affective dispositions and their aggression and peer acceptance varied as a
      function of both the emotion context (baseline vs. aggression related) and the
      particular emotion involved (happiness vs. anger). Emotion knowledge and
      affective dispositions overlapped little with each other, and both made
      independent contributions to peer acceptance and aggression. Mediation analyses
      revealed, however, that the significant connections between children's emotional
      dispositions and knowledge and their peer acceptance were mostly mediated by
      aggression.

PMID- 10902697
TI  - Preschoolers' use of form class cues in word learning.
AB  - Three experiments were conducted, involving a total of 180 2 1/2-5-year-old
      children. The experiments assessed the claim that preschoolers override form
      class cues in the interest of honoring word-meaning assumptions when they acquire
      new labels. Children were asked to choose an unlabeled- or a labeled-category
      object as the referent of a novel word modeled syntactically as a count noun or
      an adjective (Experiment 1) or as a count noun, adjective, or proper name
      (Experiments 2 and 3). Participants' interpretations of the word were also
      assessed (Experiment 3). Unlike many previous results, results of the present
      study demonstrate that children respect the form class cues when these cues and
      word-meaning assumptions suggest conflicting interpretations. It is proposed that
      past findings underestimate the robustness of form class cues as sources of
      information for preschoolers about the meanings of new words.

PMID- 10902698
TI  - Aggression in childhood and long-term unemployment in adulthood: a cycle of
      maladaptation and some protective factors.
AB  - The present study was designed to shed light on specific risk mechanisms and
      protective factors in the relation between aggression in childhood and long-term
      unemployment in adulthood. Participants were drawn from the ongoing Jyvaskyla
      Longitudinal Study of Personality and Social Development; data gathered at the
      ages of 8 (N = 369), 14, 27, and 36 years (n = 311) were used in the present
      study. Teacher-rated aggression at age 8 was related to subsequent long-term
      unemployment through a cycle of maladaptation. Specifically, childhood aggression
      predicted school maladjustment at age 14, which was both directly and indirectly
      (via problem drinking and lack of occupational alternatives at age 27) related to
      long-term unemployment. Child-centered parenting and prosocial tendencies in an
      aggressive child significantly lowered his or her probability of becoming long
      term unemployed in adulthood.

PMID- 10902699
TI  - Memory retrieval by 18--30-month-olds: age-related changes in representational
      flexibility.
AB  - Deferred imitation was used to trace changes in memory retrieval by 18-30-month
      olds. In all experiments, an adult demonstrated 2 sets of actions using 2
      different sets of stimuli. In Experiments 1A and 1B, independent groups of
      infants were tested immediately or after a 24-hr delay. Each infant was tested
      with 1 set of stimuli from the original demonstration and 1 set of stimuli that
      was different. Recall of the target actions when tested with different stimuli
      increased as a function of age, particularly after a delay. In Experiment 2,
      infants were provided with a unique verbal label for the stimuli during the
      demonstration and the test. The verbal label facilitated performance by 24-month
      olds tested with different stimuli but had no effect on performance by 18-month
      olds. One hallmark of memory development appears to be an age-related increase in
      the range of effective retrieval cues for a particular memory.

PMID- 10902700
TI  - Connectedness and autonomy support in parent-child relationships: links to
      children's socioemotional orientation and peer relationships.
AB  - Connectedness and autonomy support in the parent-child relationship are
      constructs that emerge from object relations and attachment theories but that
      overlap with other commonly studied qualities of parent-child relationships to
      provide a unifying focus for research in this domain. In this study, these
      constructs were examined in relation to children's relational competence,
      including socioemotional orientation, friendship, and peer acceptance.
      Semistructured conversations between mothers and their 5-year-olds (N = 192) were
      videotaped at home and rated for (a) connectedness between the members of the
      dyad and (b) the parent' s support for the child's autonomy. Results showed that
      connectedness was correlated with children's socioemotional orientations, number
      of mutual friendships, and peer acceptance and that the relation between parent
      child connectedness and children's peer relationships was mediated by children's
      prosocial-empathic orientation. Implications of these findings for theories that
      link parent-child relationships to the development of relational competence in
      children are discussed.

PMID- 10902702
TI  - Effects of gesture and target on 12- and 18-month-olds' joint visual attention to
      objects in front of or behind them.
AB  - Factors affecting joint visual attention in 12- and 18-month-olds were
      investigated. In Experiment 1 infants responded to 1 of 3 parental gestures:
      looking, looking and pointing, or looking, pointing, and verbalizing. Target
      objects were either identical to or distinctive from distractor objects. Targets
      were in front of or behind the infant to test G. E. Butterworth's (1991b)
      hypothesis that 12-month-olds do not follow gaze to objects behind them. Pointing
      elicited more episodes of joint visual attention than looking alone. Distinctive
      targets elicited more episodes of joint visual attention than identical targets.
      Although infants most reliably followed gestures to targets in front of them,
      even 12-month-olds followed gestures to targets behind them. In Experiment 2
      parents were rotated so that the magnitude of their head turns to fixate front
      and back targets was equivalent. Infants looked more at front than at back
      targets, but there was also an effect of magnitude of head turn. Infants'
      relative neglect of back targets is partly due to the "size" of adult's gesture.

PMID- 10902701
TI  - The role of visual and body movement information in infant search.
AB  - Three experiments investigated the use of visual input and body movement input
      arising from movement through the world on spatial orientation. Infants between 9
      1/2 and 18 months participated in a search task in which they searched for a toy
      hidden in 1 of 2 containers. Prior to beginning search, either the infants or the
      containers were rotated 180 degrees; these rotations occurred in a lit or dark
      environment. These experiments were distinguished by the environmental cues for
      object location; Experiment 1 used a position cue, Experiment 2 a color cue, and
      Experiment 3 both position and color cues. Accuracy was better in Experiments 2
      and 3 than in Experiment 1. All studies found that search was best after infant
      movement in the light; all other conditions led to equivalently worse
      performance. These results are discussed relative to a theoretical
      characterization of spatial coding focusing on the uses of spatial information.

PMID- 10902703
TI  - Molecular evolution and phylogeny of the atpB-rbcL spacer of chloroplast DNA in
      the true mosses.
AB  - The nucleotide variation of a noncoding region between the atpB and rbcL genes of
      the chloroplast genome was used to estimate the phylogeny of 11 species of true
      mosses (subclass Bryidae). The A+T rich (82.6%) spacer sequence is conserved with
      48% of bases showing no variation between the ingroup and outgroup. Rooted at
      liverworts, Marchantia and Bazzania, the monophyly of true mosses was supported
      cladistically and statistically. A nonparametric Wilcoxon Signed-Ranks test Ts
      statistic for testing the taxonomic congruence showed no significant differences
      between gene trees and organism trees as well as between parsimony trees and
      neighbor-joining trees. The reconstructed phylogeny based on the atpB-rbcL spacer
      sequences indicated the validity of the division of acrocarpous and pleurocarpous
      mosses. The size of the chloroplast spacer in mosses fits into an evolutionary
      trend of increasing spacer length from liverworts through ferns to seed plants.
      According to the relative rate tests, the hypothesis of a molecular clock was
      supported in all species except for Thuidium, which evolved relatively fast. The
      evolutionary rate of the chloroplast DNA spacer in mosses was estimated to be
      (1.12 +/- 0.019) x 10(-10) nucleotides per site per year, which is close to the
      nonsynonymous substitution rates of the rbcL gene in the vascular plants. The
      constrained molecular evolution (total nucleotide substitutions, K approximately
      0.0248) of the chloroplast DNA spacer is consistent with the slow evolution in
      morphological traits of mosses. Based on the calibrated evolutionary rate, the
      time of the divergence of true mosses was estimated to have been as early as 220
      million years ago.

PMID- 10902704
TI  - Construction of a long-range YAC physical map spanning the 10-cM region between
      the markers D18Mit109 and D18Mit68 on mouse proximal chromosome 18.
AB  - Four yeast artificial chromosome (YAC) contigs, physically approximately 8 Mb,
      have been constructed spanning a 10-cM region on mouse proximal chromosome 18 and
      include the sites of 21 known genes, including those near the twirler (Tw) locus
      and the recently isolated Niemann-Pick type C1 (npc1) gene, formerly designated
      as the spm locus. This physical map consists of 49 YAC clones that cover roughly
      15% of the chromosome. The physical order of 38 microsatellite sequence-tagged
      sites (STSs) could be assembled and confirmed based on their presence or absence
      in individual YACs, from proximal D18Mit109 through distal D18Mit68. These YACs
      provide an important resource for the further characterization and identification
      of known and unknown genes. The physical map has been integrated with our
      previously published genetic linkage map and showed an average genetic to
      physical distance of cM/Mb > 1.1.

PMID- 10902705
TI  - Repetitive A-T rich DNA sequences from the Y chromosome of the Mediterranean
      fruit fly, Ceratitis capitata.
AB  - Copies of a repetitive DNA sequence distributed over 90% of the length of the
      long arm of the Y chromosome of the Mediterranean fruit fly, Ceratitis capitata
      (medfly), have been characterized. Sequencing reveals that these repeats, ranging
      in size from approximately 1.3 to 1.7 kb, are A-T rich overall (67%). In most
      cases the repeat units appear to occur in tandemly linked arrays. The repeat
      copies also all contain a highly similar internal region, approximately 200 bp in
      length, with a more extreme A-T content bias. This internal region, designated as
      the AT element, exhibits an A-T content of at least 83%. This exceeds what has
      been described for any comparable element among invertebrates. Using primers
      designed from the DNA sequence, PCR amplification of an internal region
      encompassing the AT element also reveals that these sequences are present only in
      the male genome in different strains of the medfly.

PMID- 10902706
TI  - Isolation, characterization, and inheritance of microsatellite loci in alpine
      larch and western larch.
AB  - Microsatellite loci or simple sequence repeat loci (SSRs) were isolated in alpine
      larch (Larix lyallii Parl.) and western larch (Larix occidentalis Nutt.). In
      total, 14 SSR loci were characterized; two [(TCT)4, A7] came from published Larix
      DNA sequence data, one (CA)17 was obtained from a partial non-enriched alpine
      larch total genomic DNA library, and the remaining 11 loci were obtained from
      larch genomic DNAs enriched for (CA)n repeats. The SSR regions in these clones
      could be divided into three categories: perfect repeat sequences without
      interruption, imperfect repeat sequences with interruption(s), and compound
      repeat sequences with adjacent tandem simple dinucleotides. Eight of the 14 loci
      analyzed were found to be polymorphic and useful markers after silver-staining
      polyacrylamide gel electrophoresis. In addition, several SSR primers developed
      for alpine larch were able to successfully amplify polymorphic loci in its
      related species, western larch, and among other closely related taxa within the
      Larix genus. The inheritance of microsatellite loci was verified by analysis of
      haploid megagametophyte and diploid embryo tissues of progeny obtained from
      controlled crosses between western larch and alpine larch. All microsatellite
      loci analyzed had alleles that segregated according to expected Mendelian
      frequencies. Two species-specific markers (UAKLly10a and UAKLla1) allow easy and
      rapid identification of specific genetic entry of alpine larch and western larch
      at any stage in the sporophyte phase of the life cycle. Therefore, these markers
      are efficient in identifying the parental species and to validate controlled
      crosses between these two closely related species. These results are important in
      tree improvement programs of alpine larch and western larch aimed at producing
      genetically improved hybrid stock for reforestation in Western Canada and U.S.A.

PMID- 10902707
TI  - Genome size variation in Arachis hypogaea and A. monticola re-evaluated.
AB  - Genome size variation within species is a frequently reported, but still a
      controversial problem. In the present study, we re-evaluated recently published
      Feulgen densitometric data on genome size and its infraspecific variation in
      Arachis hypogaea, and also conducted measurements in one accession of its wild
      relative A. monticola. The methods applied were propidium iodide flow cytometry
      and Feulgen densitometry using Pisum sativum as an internal standard. The 2C DNA
      contents previously published cannot be confirmed, but values obtained in this
      study are about half as large. Additionally, we could not reproduce the
      previously reported 1.15-fold variation within A. hypogaea; our data indicate
      genome size stability between respective accessions of this species. Based on
      8.84 pg (2C) for Pisum sativum the DNA amounts (2C) were: 5.914 pg in A.
      hypogaea, and 5.979 pg in A. monticola.

PMID- 10902708
TI  - Arabidopsis thaliana: a source of candidate disease-resistance genes for Brassica
      napus.
AB  - Common structural and amino acid motifs among cloned plant disease-resistance
      genes (R genes), have made it possible to identify putative disease-resistance
      sequences based on DNA sequence identity. Mapping of such R-gene homologues will
      identify candidate disease-resistance loci to expedite map-based cloning
      strategies in complex crop genomes. Arabidopsis thaliana expressed sequence tags
      (ESTs) with homology to cloned plant R genes (R-ESTs), were mapped in both A.
      thaliana and Brassica napus to identify candidate R-gene loci and investigate
      intergenomic collinearity. Brassica R-gene homologous sequences were also mapped
      in B. napus. In total, 103 R-EST loci and 36 Brassica R-gene homologous loci were
      positioned on the N-fo-61-9 B. napus genetic map, and 48 R-EST loci positioned on
      the Columbia x Landsberg A. thaliana map. The mapped loci identified collinear
      regions between Arabidopsis and Brassica which had been observed in previous
      comparative mapping studies; the detection of syntenic genomic regions indicated
      that there was no apparent rapid divergence of the identified genomic regions
      housing the R-EST loci.

PMID- 10902709
TI  - Molecular mapping of QTLs conferring stay-green in grain sorghum (Sorghum bicolor
      L. Moench).
AB  - Drought resistance is of enormous importance in crop production. The
      identification of genetic factors involved in plant response to drought stress
      provides a strong foundation for improving drought tolerance. Stay-green is a
      drought resistance trait in sorghum (Sorghum bicolor L. Moench) that gives plants
      resistance to premature senescence under severe soil moisture stress during the
      post-flowering stage. The objective of this study was to map quantitative trait
      loci (QTLs) that control the stay-green and chlorophyll content in sorghum. By
      using a restriction fragment length polymorphism (RFLP) map, developed from a
      recombinant inbred line (RIL) population, we identified four stay-green QTLs,
      located on three linkage groups. The QTLs (Stg1 and Stg2) are on linkage group A,
      with the other two, Stg3 and Stg4, on linkage groups D and J, respectively. Two
      stay-green QTLs, Stg1 and Stg2, explaining 13-20% and 20-30% of the phenotypic
      variability, respectively, were consistently identified in all trials at
      different locations in two years. Three QTLs for chlorophyll content (Chl1, Chl2,
      and Chl3), explaining 25-30% of the phenotypic variability were also identified
      under post-flowering drought stress. All coincided with the three stay-green QTL
      regions (Stg1, Stg2, and Stg3) accounting for 46% of the phenotypic variation.
      The Stg1 and Stg2 regions also contain the genes for key photosynthetic enzymes,
      heat shock proteins, and an abscisic acid (ABA) responsive gene. Such spatial
      arrangement shows that linkage group A is important for drought- and heat-stress
      tolerance and yield production in sorghum. High-resolution mapping and cloning of
      the consistent stay-green QTLs may help to develop drought-resistant hybrids and
      to understand the mechanism of drought-induced senescence in plants.

PMID- 10902710
TI  - A search for diagnostic AFLP markers in Cichorium species with emphasis on endive
      and chicory cultivar groups.
AB  - The genus Cichorium consists of two widely cultivated species C. intybus
      (chicory) and C. endivia (endive) and four wild species, C. bottae, C. spinosum,
      C. calvum, and C. pumilum. A multivariate and an UPGMA (unweighted pair group
      method average) analysis based on AFLP (amplified fragment length polymorphism)
      markers were used to establish the genetic relationships among the species and
      cultivar groups of C. intybus and C. endivia. At the species level, the results
      correspond with previously obtained phylogenetic relationships in that C. bottae
      is the most divergent species, and C. intybus and C. spinosum, as well as C.
      endivia, C. pumilum, and C. calvum formed clusters. Based on the congruence
      between phylogenetic and genetic analyses, unique markers were expected for all
      species, however, hardly any specific marker was found except for C. bottae. The
      analysis of cultivar groups of C. intybus resembled the species analysis in two
      respects: (i) grouping of cultivars according to cultivar groups, and (ii) lack
      of markers unique to cultivar groups. In contrast to C. intybus, the cultivar
      series of C. endivia do not form distinct groups, which would reflect that
      crosses have been made among the various cultivar groups. The relationships among
      Cichorium species and cultivars will be useful for setting up a core collection
      of Cichorium, and stress the importance of inclusion of the wild species in the
      collection.

PMID- 10902711
TI  - Identification of RFLP markers for resistance to wheat spindle streak mosaic
      bymovirus (WSSMV) disease.
AB  - Wheat spindle streak mosaic bymovirus (WSSMV) causes an economically important
      disease of winter wheat in Europe and North America. Artificial inoculation with
      this virus to identify resistant wheat genotypes is difficult. This study was
      conducted to identify restriction fragment length polymorphism (RFLP) markers
      associated with resistance to this disease. A population, consisting of 104 F5
      recombinant inbred lines from a cross between hexaploid Triticum aestivum
      cultivars 'Geneva' (resistant) and 'Augusta' (susceptible), was evaluated for
      WSSMV symptoms under field conditions for four years. Two linked markers on the
      long arm of chromosome 2D, Xbcd1095 and Xcdo373, were determined to be associated
      with WSSMV resistance by bulked segregant analysis of the 10 most resistant and
      10 most susceptible lines. Marker Xcdo373 accounted for 79% and Xbcd1095 for 73%
      of the phenotypic variation. Our results suggest that resistance to WSSMV in this
      population is qualitative in nature and is controlled by few genes. These markers
      should be useful in the development of wheat cultivars resistant to WSSMV and
      perhaps also to wheat yellow mosaic bymovirus (WYMV).

PMID- 10902712
TI  - A matrix attachment region is located upstream from the high-molecular-weight
      glutenin gene Bx7 in wheat (Triticum aestivum L.).
AB  - A 2.2-kb nucleotide sequence rich in AT, located upstream from the Bx7 allele of
      the high-molecular-weight glutenin Glu-B1 locus in wheat (Triticum aestivum cv.
      Glenlea) was cloned following amplification by PCR. The 5' region of this
      sequence contains motifs typically found in matrix attachment regions (MARs) in
      other plants. We have shown that part of the 2.2-kb DNA binds to wheat nuclear
      matrix (NM) in vitro, at least as strongly as a known MAR (Adh1) from maize
      suggesting that there is a MAR upstream of Bx7. This MAR is approximately 800
      bases in length running from -750 to -1560 bases, relative to the start codon.
      Although the MAR is associated with a tissue-specific gene and is beside a strong
      tissue-specific promoter, the MAR sequence did not lead to tissue-specific
      expression of the beta-glucuronidase marker gene under the control of the rice
      actin promoter in various tissues. Presence of the MAR was only slightly
      beneficial with respect to expression levels, which were not greatly altered in
      transient expression assays in various wheat tissues although a slight increase
      in the number of foci was observed in leaves, which have low transformation
      efficiencies.

PMID- 10902713
TI  - Detection of QTLs for heading time and photoperiod response in wheat using a
      doubled-haploid population.
AB  - The genetic basis of heading time in wheat (Triticum aestivum L.) was
      investigated through the study of flowering under normal autumn sown field
      conditions as well as photoperiod responses under a controlled environment.
      Quantitative trait loci (QTLs) for these traits were mapped in a doubled-haploid
      (DH) population derived from a cross between the wheat cultivars 'Courtot' and
      'Chinese Spring'. A molecular marker linkage map of this cross that was
      previously constructed based on 187 DH lines and 380 markers was used for QTL
      mapping. The genome was well covered (85%) except for chromosomes 1D and 4D, and
      a set of anchor loci regularly spaced over the genome (one marker each 15.5 cM)
      was chosen for marker regression analysis. The presence of a QTL was declared at
      a significance threshold of alpha = 0.005. The population was grown under field
      conditions in Clermont-Ferrand, France during two years (1994-1995), in Norwich,
      U.K. over one year (1998), and also under controlled environments in Norwich. For
      each trait, between 2 and 4 QTLs were identified with individual effects ranging
      between 6.3% and 44.4% of the total phenotypic variation. Two QTLs were detected
      that simultaneously affected heading time and photoperiod response. For heading
      time, these two QTLs were detected in more than one year. One QTL located on
      chromosome arm 2BS near the locus Xfbb121-2B, co-segregated with the gene Ppd-B1
      known to be involved in photoperiod response. This chromosome region explained a
      large part of the variation (23.4-44.4% depending on the years or the traits).
      Another region located on chromosome arm 7BS between the loci Xfbb324-7B and
      Xfbb53-7B also had a strong effect (7.3-15.3%). This region may correspond to a
      QTL for earliness per se.

PMID- 10902714
TI  - Production of inbred progenies of diploid potatoes using an S-locus inhibitor
      (Sli) gene, and their characterization.
AB  - To develop inbred lines from self-incompatible, cultivated diploid potatoes, an S
      locus inhibitor (Sli) gene derived from a self-compatible variant of a wild
      potato species, Solanum chacoense, was incorporated into various cultivated
      diploid potatoes. The progeny was selfed twice by the action of the Sli gene to
      obtain 74 S2 inbred clones belonging to 8 families. More than 40% of them were
      either non-flowering or pollen sterile. Among the pollen fertile clones, self
      compatible clones occurred with a much lower frequency (20.9%) than expected
      (83.3%). The result demonstrated that self-compatibility was introduced and
      expressed in the gene pool of cultivated diploid potatoes by an action of the Sli
      gene, although serious inbreeding depression associated with selfing occurred.
      The genotypes of S2 inbreds were surveyed using 46 S. chacoense-specific RFLP
      (restriction fragment length polymorphism) markers covering the whole potato
      genome. More than half of the markers (67.4%) showed distorted segregation.
      Particularly, all markers on chromosome 12 were overrepresented in the S2
      inbreds. This confirms our earlier finding that the Sli gene locates on
      chromosome 12 and the alleles linked with this gene are preferentially
      transmitted because of its essential requirement for selfing.

PMID- 10902715
TI  - Homoeoallelic gene Ncc-tmp of Triticum timopheevii conferring compatibility with
      the cytoplasm of Aegilops squarrosa in the tetraploid wheat nuclear background.
AB  - A nuclear gene, Ncc-tmp1A, of Triticum timopheevii is required for the nucleus
      cytoplasm (NC) compatibility in tetraploid NC hybrids with the cytoplasm of
      Aegilops squarrosa. A euploid NC hybrid of T. durum was previously produced by
      introgressing the gene from chromosome 1A of T. timopheevii. To examine the
      possible presence of a functional homoeoallele in the G genome of T. timopheevii,
      segregation of seed viability was studied as a marker phenotype in BC1s involving
      the two types of NC hybrids, (Ae. squarrosa)-T. timopheevii and (Ae. squarrosa)
      T. turgidum. The result of these test crosses suggested that the G genome
      possesses a functional homoeoallele Ncc-tmp1G. Segregation of two RAPD (random
      amplified polymorphic DNA) markers that were closely linked to Ncc-tmp1A was
      further studied among the viable BC1s obtained from a test cross of (Ae.
      squarrosa)-T. timopheevii x T. turgidum. Some viable BC1 segregants without the
      markers were obtained, suggesting a limited degree of transmission of chromosome
      1G carrying Ncc-tmp1G. However, a similar RAPD analysis of BC1s obtained after
      backcrosses of reciprocal F1s of T. timopheevii/T. turgidum with T. turgidum
      showed random marker segregation. Thus, it was concluded that Ncc-tmp1A is not
      required for compatibility with its own cytoplasm. Southern blot analysis of the
      euploid NC hybrid using RFLP (restriction fragment length polymorphism) markers
      on the homologous group 1 chromosomes showed that Ncc-tmp1A locates in the
      centromeric region.

PMID- 10902716
TI  - Microsatellite DNA in peach (Prunus persica L. Batsch) and its use in
      fingerprinting and testing the genetic origin of cultivars.
AB  - We isolated and sequenced 26 microsatellites from two genomic libraries of peach
      cultivar 'Redhaven', enriched for AC/GT and AG/CT repeats, respectively. For 17
      of these microsatellites, it was possible to demonstrate Mendelian inheritance.
      Microsatellite polymorphism was assayed in 50 peach and nectarine cultivars. Of
      the 1300 PCRs carried out, all but two produced amplified products of the
      expected size. All microsatellites were polymorphic, showing 2-8 alleles per
      locus. Heterozygosity ranged from 0.04-0.74 (mean 0.47); the discrimination power
      (PD) ranged from 0.04-0.84 (mean 0.60). Cultivar heterozygosity varied greatly,
      with one cultivar ('Independence') being homozygous at all loci. The set of
      microsatellites discriminated all cultivars investigated, except several sport
      mutations, i.e., 'Dixitime' vs. 'Springcrest', 'Compact Redhaven' vs. 'Redhaven',
      and two pairs of cultivars, 'Venus' vs. 'Orion' and 'Elegant Lady' vs. 'Rome
      Star', whose pedigrees are controversial. We were able to analyze the paternity
      of several cultivars. In most cases, the parenthood was confirmed. The comparison
      of three long-living 'Redhaven' accessions supplied by different repositories did
      not provide any evidence of somatic instability of microsatellites. Hence,
      microsatellites, ranked according to their information content, are recommended
      as markers of choice for peach fingerprinting and suggestions are provided for
      interpreting band profiles and the correct sizing of alleles.

PMID- 10902717
TI  - Behavior of sex chromosomes, autosomes, and the spindle during nonrandom
      segregation in a flea beetle.
AB  - We have analyzed autosome, sex chromosome, and spindle behavior in spermatocytes
      of the flea beetle, Alagoasa bicolor. In this species, males have very large X
      and Y chromosomes, which, although they are never physically connected, always
      segregate to opposite spindle poles at anaphase I, thus preserving the sex ratio
      in the next generation. We find that the sex chromosomes are partitioned to a
      peripheral spindle domain early in prometaphase I and that their segregation can
      be accounted for mainly by their reorientation from the parallel to the linear
      configuration, and little by chromosome-to-pole movement. Further, the behavior
      of the autosomes and that of the sex chromosomes seem to have little to do with
      each other. Spindle elongation is minimal; barely segregating the large sex
      chromosomes into the daughter cells at telophase I.

PMID- 10902718
TI  - Inheritance and mapping of 2n-egg production in diploid alfalfa.
AB  - The production of eggs with the sporophytic chromosome number (2n eggs) in
      diploid alfalfa (Medicago spp.) is mainly associated with the absence of
      cytokinesis after restitutional meiosis. The formation of 2n eggs through
      diplosporic apomeiosis has also been documented in a diploid mutant of M. sativa
      subsp. falcata (L.) Arcang. (2n = 2x = 16), named PG-F9. Molecular tagging of 2n
      egg formation appears to be an essential step towards marker-assisted breeding
      and map-based cloning strategies aimed at investigating and manipulating
      reproductive mutants of the M. sativa complex. We made controlled crosses between
      PG-F9 and three wild type plants of M. sativa subsp. coerulea (Less.) Schm. (2n =
      2x = 16) and then hand-pollinated the F1 progenies with tetraploid plants of M.
      sativa subsp. sativa L. (2n = 4x = 32). As a triploid embryo block prevents the
      formation of 3x progenies in alfalfa because of endosperm imbalance, and owing to
      the negligible selfing rate, seed set in 2x-4x crosses was used to discriminate
      the genetic capacity for 2n-egg production. F1 plants that exhibited null or very
      low seed sets were classified as normal egg producers and plants with high seed
      sets as 2n-egg producers. A bulked segregant analysis (BSA) with RAPD (random
      amplified polymorphic DNA), ISSR (inter-simple sequence repeat), and AFLP
      (amplified fragment length polymorphism) markers was employed to identify a
      genetic linkage group related to the 2n-egg trait using one of the three F1
      progenies. This approach enabled us to detect a paternal ISSR marker of 610 bp,
      generated by primer (CA)8-GC, located 9.8 cM from a putative gene (termed Tne1,
      two-n-eggs) that in its recessive form determines 2n eggs and a 30% recombination
      genomic window surrounding the target locus. Eight additional RAPD and AFLP
      markers, seven of maternal, and one of paternal origin, significantly co
      segregated with the trait under investigation. The minimum number of quantitative
      trait loci (QTLs) controlling seed set in 2x-4x crosses was estimated by ANOVA
      and regression analysis. Four maternal and three paternal independent molecular
      markers significantly affected the trait. A paternal RAPD marker allele, mapped
      in the same linkage group of Tne1, explained 43% of the variation for seed set in
      2x-4x crosses indicating the presence of a major QTL. A map of the PG-F9
      chromosome regions carrying the minor genes that determine the expression level
      of 2n eggs was constructed using selected RAPD and AFLP markers. Two of these
      genes were linked to previously mapped RFLP loci belonging to groups 1 and 8.
      Molecular and genetic evidence support the involvement of at least five genes.

PMID- 10902719
TI  - Gene-centromere mapping of 312 loci in pink salmon by half-tetrad analysis.
AB  - We estimated recombination rates between 312 loci and their centromeres in
      gynogenetic diploid pink salmon (Oncorhynchus gorbuscha) that we produced by
      initiating development with irradiated sperm and blocking the maternal second
      meiotic division. Amplified fragment length polymorphisms (AFLPs) were
      significantly more centromeric than loci identified by three other techniques
      (allozymes, microsatellites, and PCR using primer sequences from interspersed
      nuclear elements). The near absence of AFLPs in distal regions could limit their
      utility in constructing linkage maps. A large proportion of loci had frequency of
      second division segregation (y) values approaching 1.0, indicating near complete
      crossover interference on many chromosome arms. As predicted from models of
      chromosomal evolution in salmonids based upon results with allozyme loci, all
      duplicated microsatellite loci that shared alleles (isoloci) had y values of
      nearly 1.0.

PMID- 10902720
TI  - Low-copy microsatellite markers for Pinus taeda L.
AB  - Eighteen low-copy and genomic microsatellite markers were tested for Mendelian
      inheritance and then assayed in 41 Pinus taeda L. samples drawn from five regions
      in the southern United States. The PCR products had multiple alleles, high levels
      of polymorphism, and little non-specific priming. Fifteen of the 18 markers were
      informative for a P. taeda three-generation RFLP (restriction fragment length
      polymorphism) pedigree, and a P. taeda population survey revealed three to 28
      alleles per locus. The highest allele numbers and polymorphic information content
      (PIC) values were associated with complex repeat sequences and (or) with
      sequences consisting of the longer strings of perfect repeats. The abundance of
      low- to rare-frequency alleles also accounted for high PIC values in both types
      of markers. Low-copy microsatellites are useful for the large, complex pine
      genome, especially in the absence of entire gene sequences in public databases
      and with the low levels of polymorphism in markers developed from expressed
      sequence tags (ESTs).

PMID- 10902721
TI  - Molecular analyses of a repetitive DNA sequence in wheat (Triticum aestivum L.).
AB  - A repetitive sequence designated WE35 was isolated from wheat genomic DNA. This
      sequence consists of a 320-bp repeat unit and represents approximately 0.002% of
      the total wheat DNA. It is unidirectionally distributed either continuously or
      discretely in the genome. Ladder-like banding patterns were observed in Southern
      blots when the wheat genomic DNA was restricted with endonuclease enzymes EcoRI,
      HincII, NciI, and NdeI, which is characteristic for tandemly organized sequences.
      Two DNA fragments in p451 were frequently associated with the WE35 repetitive
      unit in a majority of lambda wheat genomic clones. A 475-bp fragment homologous
      to the 5'-end long terminal repeat (LTR) of cereal retroelements was also found
      in some lambda wheat genomic clones containing the repetitive unit. Physical
      mapping by fluorescence in situ hybridization (FISH) indicated that one pair of
      wheat chromosomes could be specifically detected with the WE35 positive probe
      p551. WE35 can be considered a chromosome-specific repetitive sequence. This
      repetitive unit could be used as a molecular marker for genetic, phylogenetic,
      and evolutionary studies in the tribe Triticeae.

PMID- 10902722
TI  - Genetic analysis of vein function in the Drosophila embryonic nervous system.
AB  - The Drosophila epidermal growth factor receptor (EGFR) may be activated by two
      ligands expressed in the embryonic nervous system, Spitz and Vein. Previous
      studies have established Spitz as an essential activator of EGFR signaling in
      nervous system development. Here, we report the pattern of expression of vein
      mRNA in the nervous system and characterize the contribution of vein to cell
      lineage and axonogenesis. The number of midline glia (MG) precursors is reduced
      in vein mutants before the onset of embryonic apoptosis. In contrast to spitz,
      mis-expression of vein does not suppress apoptosis in the MG. These data indicate
      that early midline EGFR signaling, requiring vein and spitz, establishes MG
      precursor number, whereas later EGFR signals, requiring spitz, suppress apoptosis
      in the MG. vein mutants show early irregularities during axon tract
      establishment, which resolve later to variable defasciculation and thinner
      intersegmental axon tracts. vein and spitz phenotypes act additively in the
      regulation of MG cell number, but show synergism in a midline neuronal cell
      number phenotype and in axon tract architecture. vein appears to act downstream
      of spitz to briefly amplify local EGFR activation.

PMID- 10902723
TI  - Nucleolar dominance does not occur in root tip cells of allotetraploid Brassica
      species.
AB  - Using in situ hybridization and silver staining methods, the numbers of active
      and inactive rDNA loci have been established for three allotetraploid species of
      Brassica (B. napus, B. carinata, and B. juncea) and their diploid ancestors (B.
      campestris, B. nigra, and B. oleracea). The allotetraploid species have
      chromosome numbers equal to the sum of the numbers in their diploid relatives,
      but have fewer rDNA loci. All species investigated have lower numbers of active
      NORs (AgNORs, nucleolar organizer regions) compared with the numbers of rDNA
      sites revealed by in situ hybridization. The number of active rDNA loci of the
      allotetraploid species is equal to the number of AgNORs in their diploid
      ancestors, indicating the absence of nucleolar dominance in amphidiploid Brassica
      species, at least in root meristematic cells.

PMID- 10902724
TI  - A PCR product derived from female DNA with regional localization on the Y
      chromosome.
AB  - A 154-bp PCR product amplified from human female DNA mapped onto the Y chromosome
      under high-stringency in situ hybridization conditions. The female DNA sequence
      revealed an 89% homology with the HSDYZ1 sequence. When the same primers were
      used to amplify male DNA, a 154-bp DNA fragment was also obtained, showing a 98%
      homology with HSDYZ1. However, although the HSDYZ1 sequence is widely distributed
      along the long arm of the Y chromosome, both of these particular PCR products are
      di-regionally localized within this distal block of constitutive heterochromatin.
      In situ hybridization under lower stringency showed that these 154-bp sequences
      map both onto the autosomes and the Y chromosome. Overall, this paper shows (i) a
      new class of DNA sequences shared by the autosomes and the Y chromosome; and (ii)
      a substructured organization of some DNA repeats within the DYZ1 family that
      forms a large part of the constitutive heterochromatin of the Y chromosome.

PMID- 10902725
TI  - Tandemly repeated sequences in mtDNA control region of whitefish, Coregonus
      lavaretus.
AB  - Length variation of the mitochondrial DNA control region was observed with PCR
      amplification of a sample of 138 whitefish (Coregonus lavaretus). Nucleotide
      sequences of representative PCR products showed that the variation was due to the
      presence of an approximately 100-bp motif tandemly repeated two, three, or five
      times in the region between the conserved sequence block-3 (CSB-3) and the gene
      for phenylalanine tRNA. This is the first report on the tandem array composed of
      long repeat units in mitochondrial DNA of salmonids.

PMID- 10902726
TI  - Radiation damage to triplex DNA induced by gamma-rays: a footprinting study and
      Monte Carlo simulation.
AB  - PURPOSE: This study is aimed at comparing the radiosensitivity of a 21-mer DNA
      fragment in duplex and triplex form (Py x Pu duplex and Py x Pu:Py triplex) and
      to give insights into the fine structural features due to the different
      strandedness. MATERIALS AND METHODS: The triplex sample was characterized by
      means of electrophoretic mobility, circular dichroism spectra and UV melting
      experiments. Triplex and duplex, labelled on the homopyrimidine or homopurine
      strand, were irradiated with 60Co gamma-rays. The samples were analysed by
      sequencing gel electrophoresis and the patterns of relative probabilities of
      frank strand breakage (FSB) and alkali-revealed breakage (ARB) at each nucleotide
      site were determined. Relative probabilities of OH* radical attack to duplex and
      triplex DNA built up with a molecular modelling software were calculated using a
      previously reported simulation procedure (Sy et al. 1997). The experimental data
      were compared with the results of the theoretical simulations of OH* radical
      attack to DNA. RESULTS: Globally, the duplex is more attacked than the triplex,
      mainly in the Pu strand. Sequence-dependent variations of FSB and FSB+ARB
      probabilities in both duplex and triplex were revealed. No significant
      differences between the patterns of damage in the triplex and in the duplex were
      observed. CONCLUSIONS: The presence of the third Py strand located in the major
      groove of the DNA duplex modifies the total yields of radiation-induced DNA
      damage, but not the sequence-dependent patterns of relative probability of damage
      at each nucleotide site.

PMID- 10902727
TI  - Quantification of DNA damage by PFGE: development of an analytical approach to
      correct for the background distribution.
AB  - PURPOSE: To analyse the currently existing methods to infer the extent of
      cellular DNA damage induced by ionizing radiation when the pulsed field gel
      electrophoresis (PFGE) technique is used. RESULTS AND CONCLUSIONS: PFGE is
      currently the method of choice for the measurement of radiation-induced double
      strand breaks (dsb). For accurate determination of both the yields and
      distributions of breaks, separation of a large range of fragment sizes is
      required. In the conventional analysis of PFGE experiments, the background
      distribution of fractionated molecules is, normally, simply subtracted from the
      irradiated measured distribution, for each molecular weight region available.
      This work shows that this approach may lead to incorrect estimation of the
      breakage frequencies. An alternative approach based on correcting the fitting
      functions for the actual nonrandom damage present in the control unirradiated
      samples has been developed.

PMID- 10902728
TI  - Protection of DNA from radiation-induced double-strand breaks: influence of
      replication and nuclear proteins.
AB  - PURPOSE: To study the protective effect of histone and non-histone proteins on
      double-strand break (dsb) induction in replicating S-phase DNA as well as bulk
      DNA of plateau phase human tumour cells. MATERIALS AND METHODS: Induction of dsb
      was studied in two human adenocarcinoma cell lines: Colo320HSR and MCF-7. To
      assess the influence of chromatin structure on radiation-induced DNA dsb,
      different nuclear preparations of cells, either continuously labelled with 14C or
      pulse labelled with 3H, were assessed by pulsed-field gel electrophoresis (PFGE).
      RESULTS AND CONCLUSIONS: Stepwise removal of DNA-bound proteins from the
      chromatin increased the amount of radiation-induced dsb in both cell lines.
      However, the protective effect of DNA-associated proteins on dsb induction was
      significantly reduced in DNA of replicating S-phase cells compared with bulk DNA
      of plateau phase cells. These data show that proteins associated with the DNA
      have a different protective effect on radiation-induced dsb, rendering
      replicating DNA with open chromatin structure more sensitive to dsb induction by
      ionizing radiation.

PMID- 10902729
TI  - Protection from radiation-induced DNA single-strand breaks by induction of
      nuclear metallothionein.
AB  - PURPOSE: To examine the extent to which nuclear metallothionein protects from
      radiation-induced DNA damage under aerobic and hypoxic conditions. MATERIALS AND
      METHODS: A semiquantitative fluorescence image analysis method measured the
      nuclear content of metallothionein (MT) in ME180 and SiHa human squamous cervical
      carcinoma cell lines under normal growth conditions, and following MT induction
      by zinc. The extent of initial DNA damage following 60Co irradiation under
      aerobic and hypoxic conditions was assessed using the alkaline comet assay.
      RESULTS: Provided that cells were maintained at 37 degrees C, most of the
      cellular content of MT was in the nucleus. Incubation at 4 degrees C caused the
      rapid translocation of MT from the nucleus into the cytoplasm in both cell lines,
      with no net loss of cellular MT. Baseline nuclear MT levels were about four times
      greater in ME180 cells, and were much more readily induced by treatment with 100
      microM zinc acetate, compared with SiHa cells. Under aerobic conditions, MT
      induction by zinc resulted in no protection in either of the cell lines. Under
      hypoxic conditions, however, the number of DNA single-strand breaks in zinc
      treated cells was reduced by approximately 40% in ME180, but not in SiHa cells,
      when compared with non-induced controls. CONCLUSIONS: Nuclear MT can exert a
      significant level of protection from radiation by a mechanism that involves
      competition with oxygen for DNA radical sites and/or scavenging of free radicals.
      Because increased MT levels have been reported in hypoxic micro-regions of some
      solid tumours, this protective mechanism might have clinical relevance.

PMID- 10902730
TI  - Critical energies for ssb and dsb induction in plasmid DNA by vacuum-UV photons:
      an arrangement for irradiating dry or hydrated DNA with monochromatic photons.
AB  - PURPOSE: Theoretical modelling techniques are often used to simulate the action
      of ionizing radiations on cells at the nanometre level. Using monoenergetic
      vacuum-UV (VUV) radiation to irradiate DNA either dry or humidified, the action
      spectra for the induction of DNA damage by low energy photons and the role of
      water and can be studied. These data provide inputs for the theoretical models.
      METHODS: Various combinations of monochromator, grating and VUV window have been
      used to obtain monochromatic photons from the 2 GeV electron synchrotron at the
      CLRC, Daresbury Laboratory. A sample chamber containing plasmid DNA is installed
      at the end of the beamline. The chamber can be evacuated or water can be
      introduced (as water vapour or humidified helium). In this way, DNA can be
      irradiated either dry or humidified. RESULTS: An arrangement for irradiating dry
      or humidified DNA using monoenergetic photons from 7 eV to 150 eV has been
      developed. At the energies used, exposure rates vary from about 5 x 10(10) to 3 x
      10(12) photons cm(-2) s(-1) over a 1 cm2 sample area. At all but the lowest
      energies this is sufficient to produce significant levels of DNA damage in just a
      few minutes. The measured dose variation over the sample area is typically 30%,
      but this is reduced significantly using sample scanning techniques.

PMID- 10902731
TI  - Relationship between cellular radiosensitivity and non-repaired double-strand
      breaks studied for different growth states, dose rates and plating conditions in
      a normal human fibroblast line.
AB  - PURPOSE: The aim of this study was to test under which conditions non-repaired
      DNA double-strand breaks (dsb) could be used as an indicator of cellular
      radiosensitivity of normal human fibroblasts. MATERIALS AND METHODS: The
      experiments were performed with a primary normal skin fibroblast line (NFHH)
      derived from a healthy donor. Cells were X-irradiated either in exponential or
      confluent state with high (4 Gy/min) or low dose rate (0.04 Gy/min) and either
      plated immediately or delayed after irradiation. The fraction of clonogenic cells
      was determined after doses up to 12 Gy using colony forming assay and the number
      of non-repaired dsb were measured 24 h after X-irradiation with doses up to 180
      Gy using constant-field gel electrophoresis. RESULTS: Cellular radiosensitivity
      of NFHH cells was found to depend on all three conditions tested. In contrast,
      the number of non-repaired dsb was found to depend on dose rate and growth state
      only. There were, however, no differences for the plating conditions tested. This
      result was attributed to the almost complete inhibition of cell-cycle progression
      when cells were plated immediately after irradiation. For the two dose rates and
      growth conditions, differences in non-repaired dsb were found to correspond with
      the respective differences measured for the cellular radiosensitivity, and these
      data agreed fairly well with the correlation previously found for 11 fibroblast
      lines varying in dsb repair capacity. CONCLUSIONS: For irradiation followed by
      delayed plating only, non-repaired dsb can be used to predict the cellular
      radiosensitivity.

PMID- 10902732
TI  - The effects of microgravity on ligase activity in the repair of DNA double-strand
      breaks.
AB  - PURPOSE: In recent years, contradictory data have been reported about the effects
      of microgravity on radiation-induced biological responses in space experiments.
      The aim of the present study was to clarify whether enzymatic repair of DNA
      double-strand breaks is affected by microgravity using an in vitro enzymatic
      reaction system. MATERIALS AND METHODS: The DNA repair activity of T4 DNA ligase
      (EC 6.5.1.1) was measured in vitro for a DNA substrate damaged by restriction
      enzyme digestion during a US Space Shuttle mission (Discovery; STS-91). After the
      flight, the amount of ligated DNA molecules was measured using an electrophoresis
      method. RESULTS: Ligated products (closed circular DNA, open circular DNA and
      multimeric ligated products) were produced by T4 DNA ligase treatment of linear
      DNA containing double-strand breaks, and they increased with increasing T4 DNA
      ligase concentration (0-3 units per microg of plasmid DNA). Almost no difference
      in T4 DNA ligase activity was detected between the space experiments and the
      control ground experiments. CONCLUSIONS: No significant effect of microgravity on
      ligation of damaged DNA was found during space flight. Therefore, other
      mechanisms must account for the synergism between radiation and microgravity, if
      it exists.

PMID- 10902733
TI  - DNA damage formation, DNA repair, and survival after exposure of DNA repair
      proficient and nucleotide excision repair-deficient human lymphoblasts to UVA1
      and UVB.
AB  - PURPOSE: The comet assay has been used to visualize DNA damage in single cells
      after exposure to UV light. These comets are commonly thought to reflect
      transient, repair-induced DNA breaks. The goal of the work presented here was to
      further characterize the nature of UV-induced comets and to further elucidate DNA
      damage formation by different wavelengths of ultraviolet light. MATERIALS AND
      METHODS: Detailed dose-response and time-course experiments with comet formation
      were carried out with normal and nucleotide excision repair (NER)-deficient
      xeroderma pigmentosum (XP) lymphoblasts. Irradiation was carried out with low,
      intermediate, or high doses of UVA1 or UVB, comet formation was observed, cell
      survival and viability were determined, and UV-induced apoptosis was measured.
      RESULTS: All responses were dose-dependent. With the intermediate dose of UVA1, a
      pronounced comet formation was observed without subsequent growth inhibition.
      Raising levels of porphyrins, which act as photosensitizers, by preincubation
      with 5-amino-levulinic acid increased comet formation with UVA1, but not with
      UVB. UVA1-sensitivity and comet formation in XP cells was not significantly
      different from the normal cells. With UVB no comet formation was seen without
      subsequent apoptotic cell death. XP cells exhibited the known UVB
      hypersensitivity, but their comet formation was not significantly different from
      that of normal cells. CONCLUSIONS: The findings are compatible with the
      hypothesis that UV-induced comets represent transient repair-induced DNA breaks.
      Both, the NER of dimers and the base excision repair of oxidative DNA
      modifications are thought to contribute to comet formation.

PMID- 10902734
TI  - Dose- and time-response relationships for lethal mutations and chromosomal
      instability induced by ionizing radiation in an immortalized human keratinocyte
      cell line.
AB  - PURPOSE: To investigate the relationship between two well-established delayed
      effects of ionizing radiation, experiments were conducted to determine the
      induction and expression of lethal mutations (delayed reproductive death) and
      chromosomal instability with respect to dose and time in a human immortalized
      keratinocyte cell line. METHODS: HPV-G cells were gamma- or alpha-irradiated and
      maintained in culture for up to 72 population doublings. At intervals,
      measurements were made of cloning efficiency and the cells examined for apoptosis
      and cytogenetic aberrations. RESULTS: The descendants of cells surviving 1 or 3
      Gy gamma-irradiation, but not 0.5 Gy gamma-irradiation, exhibited a reduced
      colony-forming efficiency. The reduction persisted at a constant rate of 15-20%
      clonogenic cell loss per population doubling for up to 72 population doublings.
      Apoptosis was demonstrated in all colonies in the 1 and 3 Gy groups at 30 and 72
      population doublings post-irradiation but not in the 0.5 Gy group. A significant
      persistent reduction in colony-forming ability (approximately 80%) was
      demonstrated in the progeny of cells irradiated with 0.5 Gy alpha-particles.
      After 30 population doublings, the proportion of chromosomally aberrant cells was
      significantly greater than control values for all doses of both high- and low-LET
      radiations. The major cytogenetic aberrations (chromatid breaks, chromosome
      fragments and minutes) were consistent with the transmission of chromosomal
      instability. The expression of instability declined between 30 and 72 population
      doublings in the 0.5 Gy and 3 Gy gamma-irradiation groups, but persisted up to 72
      population doublings in the 1 Gy group. The expression of chromosomal instability
      was greater in the descendants of alpha-irradiated cells and showed little
      evidence of reduction with time. CONCLUSIONS: Unstable aberrations characteristic
      of radiation-induced chromosomal instability may commonly result in apoptosis and
      account for a component of the delayed reproductive death/lethal mutation
      phenotype in HPV-G cells. However, the absence of lethal mutations in the
      descendants of 0.5 Gy gamma-irradiated cells indicates a low-LET threshold effect
      for this particular endpoint. Overall, and particularly at low doses, there is no
      direct correlation between the two endpoints, indicating the absence of a simple
      relationship between these manifestations of radiation-induced genomic
      instability.

PMID- 10902735
TI  - Discrimination between complete and incomplete chromosome exchanges in X
      irradiated human lymphocytes using FISH with pan-centromeric and chromosome
      specific DNA probes in combination with telomeric PNA probe.
AB  - PURPOSE: To discriminate precisely between radiation-induced complete and
      incomplete chromosome exchanges using chromosome painting together with the
      detection of the centromeres and telomeres in one FISH assay. MATERIALS AND
      METHODS: Human lymphocytes were exposed in vitro to X-rays at a dose of 4 Gy.
      Chromosome aberrations were analysed using the FISH technique in combination with
      a whole chromosome-specific DNA probe for chromosome 8, human pan-centromeric DNA
      and telomeric PNA probes. RESULTS: The combined FISH assay has improved the
      resolution of detecting chromosomal exchanges in human lymphocytes. Results
      indicate that the frequency of observed incomplete exchange patterns was 21% when
      telomeric signals were ignored during the analysis. When the telomeric signals
      were included in the analysis a large proportion of apparently incomplete
      exchange patterns appeared complete and should be re-classified. The percentage
      of true incomplete exchanges was found to be less than 5%. CONCLUSION: The
      combination of chromosome painting and the detection of centromeres and telomeres
      enable unequivocal discrimination between incomplete and complete exchanges. The
      fraction of true incomplete exchanges observed in X-irradiated human lymphocytes
      was found to be low in comparison with previous reports in the literature.

PMID- 10902736
TI  - Influence of the sampling time on chromosomal aberrations at G2 phase in Syrian
      hamster embryonic cells irradiated with different types of radiation.
AB  - PURPOSE: To investigate the time-course of chromosomal aberrations following
      radiations of differing LET. MATERIALS AND METHODS: Syrian hamster embryonic
      cells were irradiated with nitrogen ions (LET(infinity) = 530 keV/microm) and
      helium-ions (LET(infinity) = 36 and 77 keV/microm), also 137Cs gamma-rays as a
      reference radiation. The frequency of chromatid-type aberrations was determined
      after 0-6 h incubation in a 5% CO2 incubator at 37 degrees C. RESULTS: The amount
      of chromosomal damage per cell for nitrogen ions detected immediately after
      irradiation was lower than induced by 137Cs gamma-rays. In contrast, helium ions
      were more effective than gamma rays in inducing chromatid type damage. The RBE
      values for the nitrogen-ion beams were 0.45 for gaps, 0.43 for deletions and 0.20
      for exchanges. For helium-ion beams, the RBE values for the 36 keV/microm beams
      and the 77 keV/microm beams were 1.2 and 1.5 for gaps, 1.3 and 2.1 for deletions,
      and 1.5 and 1.9 for exchanges, respectively. The frequency of cells with
      chromosomal damage following exposure to gamma-rays and helium-ion beams showed a
      downward trend with increasing incubation period. In contrast, in the case of
      nitrogen-ion beams, there was an increase with the incubation period.
      CONCLUSIONS: The results show that it is possible to underestimate chromosomal
      damage for different types of radiation by scoring aberrations at a single fixed
      sampling time.

PMID- 10902737
TI  - Kinetics of formation of exchanges and rejoining of breaks in human G0 and G2
      lymphocytes after low-LET radiation.
AB  - PURPOSE: To study the kinetics of chromosomal break rejoining and exchange
      formation in human G0 and G2 lymphocytes after low-LET irradiation using the
      premature chromosome condensation (PCC) technique. METHODS: For the G0
      experiments, isolated human lymphocytes were irradiated (1, 3 and 8 Gy) and
      immediate and delayed fusions (1, 3, 5, 8 and 24 h) were performed with CHO
      cells, and 48-h cultures were set up simultaneously. Interphase and metaphase
      human chromosomes were hybridized with dual colour combination probes for
      chromosomes 2 and 4. For the G2 experiments, isolated lymphocytes from the same
      donor were cultured for 69 h, irradiated with 3 Gy 60Co gamma rays and fused with
      CHO cells immediately and after 1, 2 and 3 h. Chromatid breaks and exchanges were
      scored after Giemsa staining. RESULTS: In both G0 and G2 cells, exchanges were
      already observed at the first fusion and, at lower doses, their frequencies
      remained relatively stable over time. The exchange-type aberrations seen in G0
      cells were mostly incomplete, especially in the first fusions, while the
      exchanges seen in metaphase were mostly complete. The frequency of complete
      exchanges increased by time during incubation, while the frequency of incomplete
      exchanges showed more variation and a general decline by time in the G0-PCC
      experiment. The number of breaks declined rapidly by time both in G0 and G2. The
      break rejoining rate was higher at 8 Gy than in the two lower doses in the G0
      PCC. The overall aberration frequencies in G0 and G2 cells studied by PCC were
      higher than in the corresponding metaphase. The initial number of breaks in G2
      was higher than in G0 and the break rejoining rate in the G2 was two-fold.
      CONCLUSIONS: The formation of complete exchanges in G0 is a delayed process. The
      incomplete exchanges appear unstable in G0. The decreasing proportion of
      incomplete exchanges and simultaneous increase in complete exchanges in G0-PCC
      indicates that formation of exchanges is not coordinated in time.

PMID- 10902738
TI  - Inactivation of human normal and tumour cells irradiated with low energy protons.
AB  - PURPOSE: To analyse the cell inactivation frequencies induced by low energy
      protons in human cells with different sensitivity to photon radiation. MATERIALS
      AND METHODS: Four human cell lines with various sensitivities to photon
      irradiation were used: the SCC25 and SQ20B derived from human epithelium tumours
      of the tongue and larynx, respectively, and the normal lines M/10, derived from
      human mammary epithelium, and HF19 derived from a lung fibroblast. The cells were
      irradiated with y-rays and proton beams with linear energy transfer (LET) from 7
      to 33 keV/microm. Clonogenic survival was assessed. RESULTS: Survival curves are
      reported for each cell line following irradiation with gamma-rays and with
      various proton LETs. The surviving fraction after 2 Gy of gamma-rays was 0.72 for
      SQ20B cells, and 0.28-0.35 for the other cell lines. The maximum LET proton
      effectiveness was generally greater than that of gamma-rays. In particular there
      was a marked increase in beam effectiveness with increasing LET for the most
      resistant cells (SQ20B) whose 2 Gy-survival varied from 0.72 with gamma-radiation
      down to 0.37 with 30 keV/microm protons. The relative biological effectiveness
      (RBE(2 Gy gamma)) with the 30 keV/microm beam, evaluated as the ratio of 2 Gy to
      the proton dose producing the same inactivation level as that given by 2 Gy of
      gamma-rays, was 3.2, 1.8, 1.3 and 0.8 for SQ20B, M/10, SCC25, and HF19,
      respectively. CONCLUSIONS: RBE for inactivation with high-LET protons increased
      with the cellular radioresistance to gamma-rays. The cell line with the greatest
      resistance to gamma-rays was the most responsive to the highest LET proton beam.
      A similar trend has also been found in studies reported in the literature with
      He, C, N ions with LET in the range 20-125 keV/microm on human tumour cell lines.

PMID- 10902740
TI  - Absence of the effects of 50 Hz magnetic fields on the progression of acute
      myeloid leukaemia in rats.
AB  - PURPOSE: As the most recent epidemiological studies provide no definite
      conclusions about the effects of 50/60 Hz magnetic fields (MFs) on the incidence
      of leukaemia in humans, animal models in a well-controlled environment are useful
      for evaluating the possibility of an association between MFs and leukaemia. The
      present study was designed to determine whether 50 Hz magnetic fields can alter
      the progression of leukaemia. MATERIALS AND METHODS: A well-characterized model
      of transplantable acute myeloid leukaemia in rats was used for the first time.
      This model is closely related to human acute myeloid leukaemia, the type most
      frequently reported in epidemiological studies of adults. After leukaemic cell
      implantation, rats were exposed to a sinusoidal 50 Hz MF of 100 microT for 18 h a
      day, 7 days a week, throughout leukaemia progression. The parameters investigated
      were: survival time, body weight, haematologic parameters, infiltration of blood,
      bone marrow, spleen and liver by leukaemic cells. RESULTS: The results showed no
      significant changes (p > 0.05) in leukaemic MF-exposed versus unexposed rats for
      any of the parameters involved in leukaemia progression. CONCLUSION: These data
      do not support the hypothesis that 50 Hz magnetic fields influence leukaemia
      progression in humans.

PMID- 10902741
TI  - Specific helium-neon laser sensitivity of the purified cytochrome c oxidase.
AB  - PURPOSE: In order to gain some insight into the mechanism of interaction between
      Helium-Neon (He-Ne) laser light and mitochondrial cytochromes, the sensitivity of
      cytochrome electron transfer activity to He-Ne laser was tested. MATERIALS AND
      METHODS: Irradiation of solutions containing either purified cytochromes or
      dissolved rat liver mitochondria was carried out (wavelength 632.8 nm, fluence
      rate 10 mW cm(-2), fluence 2 J cm(-2)); the irradiation conditions were the ones
      able to affect cytochrome c oxidase (COX) activity in mitochondria (Pastore et
      al., 1994). RESULTS: Cytochrome c oxidation catalysed by COX was affected by He
      Ne laser irradiation of the purified enzyme. This result was obtained from
      measurements of the pseudo-first-order kinetic constant and from determinations
      of the turnover number of the enzyme, performed at different cytochrome c/COX
      ratios. Consistently, the kinetic parameters of COX changed. On the contrary, no
      alteration in the rate of electron transfer catalysed by either cytochrome c or
      bc1 complex was found. CONCLUSIONS: This study shows that purified COX is a
      specific target of He-Ne laser light; therefore, COX may be considered to be a
      mitochondrial photo-acceptor.

PMID- 10902739
TI  - ATM protein is required for radiation-induced apoptosis and acts before
      mitochondrial collapse.
AB  - PURPOSE: To define the role of the ataxia telangiectasia (A-T) mutated gene (ATM)
      in activation and progress of apoptosis. MATERIAL AND METHODS: Three normal and
      three A-T EBV-transformed cell lines were studied. Following irradiation (IR),
      Fas activation or ceramide exposure, viability and apoptosis were measured by
      trypan blue dye exclusion assay and as sub-G1 cell fraction by flow cytometric
      analysis of propidium iodide stained cultures, respectively. Activation of
      caspase-3 was evaluated by immunoblot and by an in vitro activity assay on
      cytosolic cell extracts. To assess changes in mitochondrial potential and
      reactive oxygen species, cells were stained by 3,3'-dihexyloxacarbocynine iodide
      or hydroethidine, respectively, and scored by flow cytometry. RESULTS: The
      observations establish that A-T cells are equipped with a proficient apoptotic
      machinery, as demonstrated by their ability to undergo mitochondrial collapse and
      caspase-3 activation after Fas activation or ceramide treatment. Both treatments
      have a similar cytotoxic effect on normal and A-T cells. In contrast, in spite of
      the stronger cytotoxicity induced by IR exposure, irradiated A-T cells are unable
      to undergo mitochondrial collapse and caspase-3 activation. CONCLUSIONS: The data
      indicate that ATM is necessary in the initiation of molecular pathway(s) leading
      to IR-induced apoptosis, and suggest that increased radiosensitivity of A-T cells
      is more likely a direct consequence of necrotic cell death.

PMID- 10902742
TI  - The effect of evening primrose oil on the radiation response and blood flow of
      mouse normal and tumour tissue.
AB  - PURPOSE: To investigate the effect of the oral administration of evening primrose
      oil on the radiation response and the blood flow of normal tissue and a tumour in
      BALB/c mice. METHODS AND MATERIALS: Aliquots of evening primrose oil were fed to
      BALB/c mice daily and the radiation response of the skin was assessed by the
      determination of ED50 values for the incidence of moist desquamation, using
      probit analysis. Tumour radiosensitivity was investigated by determining the
      growth delay caused by irradiation of a transplantable rhabdomyosarcoma. The
      86RbCl uptake technique was used to determine the blood flow in normal foot and
      tumour tissue. The fatty-acid content of red blood cells, plasma and tumour
      tissue was measured using gas chromatography. RESULTS: Daily evening primrose oil
      dietary supplementation reduced the sensitivity of skin to radiation-induced
      moist desquamation and prevented the radiation-associated increase in blood flow
      that was observed in this tissue. No modification of tumour blood flow or of
      tumour sensitivity to radiation resulted from evening primrose oil
      supplementation of mice. Evening primrose oil supplementation resulted in changes
      in plasma levels of linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma
      linolenic acid (DGLA) and arachidonic acid (AA). These changes were contingent on
      whether the mice had been irradiated or not. In red blood cells evening primrose
      oil supplementation increased the GLA level of unirradiated mice and the LA level
      at 20 days after irradiation. There were no changes in tumour fatty-acid levels
      as a result of evening primrose oil treatment. CONCLUSIONS: Daily evening
      primrose oil supplementation reduced the sensitivity of skin to radiation-induced
      moist desquamation but did not alter tumour sensitivity to radiation.

PMID- 10902743
TI  - Current evidence for the induction of autoimmune rheumatic manifestations by
      cytokine therapy.

PMID- 10902744
TI  - Occupational physical activities and osteoarthritis of the knee.
AB  - OBJECTIVE: To assess the risk of knee osteoarthritis (OA) associated with
      kneeling, squatting, and other occupational activities. METHODS: We compared 518
      patients who were listed for surgical treatment of knee OA and an equal number of
      control subjects from the same communities who were matched for sex and age.
      Histories of knee injury and occupational activities were ascertained at
      interview, height and weight were measured, and the hands were examined for
      Heberden's nodes. Data were analyzed by conditional logistic regression. RESULTS:
      After adjustment for body mass index (BMI), history of knee injury, and the
      presence of Heberden's nodes, risk was elevated in subjects who reported
      prolonged kneeling or squatting (odds ratio [OR] 1.9; 95% confidence interval
      [95% CI] 1.3-2.8), walking >2 miles/day (OR 1.9; 95% CI 1.4-2.8), and regularly
      lifting weights of at least 25 kg (OR 1.7; 95% CI 1.2-2.6) in the course of their
      work. The risks associated with kneeling and squatting were higher in subjects
      who also reported occupational lifting, and appeared to interact multiplicatively
      with the risk conferred by obesity. People with a BMI of > or =30 kg/m2 whose
      work had entailed prolonged kneeling or squatting had an OR of 14.7 (95% CI 7.2
      30.2), compared with subjects with a BMI <25 kg/m2 who were not exposed to
      occupational kneeling or squatting. CONCLUSION: There is now strong evidence for
      an occupational hazard of knee OA resulting from prolonged kneeling and
      squatting. One approach to reducing this risk may lie in the avoidance of obesity
      in people who perform this sort of work.

PMID- 10902745
TI  - A cotwin control study of the relationship between hip osteoarthritis and bone
      mineral density.
AB  - OBJECTIVE: Previous case-control studies have shown various degrees of inverse
      relationship between osteoarthritis (OA) and osteoporosis (OP). The aim of this
      study was to examine the relationship between radiographic hip OA and bone
      mineral density (BMD) at the affected and contralateral hips, as well as at more
      distal sites. We also explored the possibility that this association might be
      confounded by genetic factors. METHODS: Using the discordant twin model to reduce
      selection bias and adjust for genetic factors, plain pelvic radiographs of white
      female twins aged >40 years, from the St. Thomas' UK Adult Twin Register, were
      assessed for radiographic features of hip OA. Overall OA was classified using a 6
      point global grading system (Croft). Osteophytes (OPH) and joint space narrowing
      (JSN) were also examined separately. BMD was measured by dual x-ray
      absorptiometry at the left hip, lumbar spine, and total body. The association of
      OA with BMD was assessed using conditional logistic regression. Adjustments were
      made for body mass index, lifetime physical activity, menopausal status, use of
      estrogen, and smoking. RESULTS: The analysis included a total of 1,148 women
      comprising 160 monozygotic and 414 dizygotic twin pairs. The median age of the
      twins was 53 years (range 40-70). The crude and adjusted odds ratios and 95%
      confidence intervals for having radiographic features of hip OA were 1.63 (1.06,
      2.50) and 1.80 (1.05, 3.12), respectively, per unit difference in standardized
      BMD of the ipsilateral femoral neck. The presence of OPH, but not JSN, was
      associated with higher BMD. Twins with hip OPH had 3.5% higher femoral neck BMD
      than their unaffected cotwins. No clear association was found between hip OA and
      BMD at the contralateral site, lumbar spine, or total body. CONCLUSION: This twin
      study confirms the existence of an inverse relationship between OA and OP at the
      hip. However, the relationship was localized to the OA-affected hip. The
      generalized and greater increase in BMD in osteoarthritic subjects seen in
      previous studies of unrelated populations is therefore likely to be due, in part,
      to genetic factors shared by hip OA and high bone mass. It also suggests that
      local changes in bone density may be a component of the disease process in hip
      OA.

PMID- 10902747
TI  - A comparison of three radiologic scoring systems for the long-term assessment of
      rheumatoid arthritis: findings of an ongoing prospective inception cohort study
      of 132 women followed up for a median of twelve years.
AB  - OBJECTIVE: To compare the sensitivity and efficiency of 3 different radiologic
      scoring systems in measuring radiologic progression of rheumatoid arthritis (RA)
      over a 12-year period. METHODS: Radiographs of the hands and feet of 112 RA
      patients were assessed at 0, 3, 6, and 12 years of disease duration using the
      Sharp score as modified by van der Heijde (SHS), the Sharp score with increased
      maximum scores (Sharp Max), and the Kellgren score. The sensitivity to change was
      tested using the standardized response mean (SRM); the efficiency was determined
      by calculating the number of patients needed to detect 50% difference in
      progression between 2 patient groups. RESULTS: Radiologic abnormalities were
      steadily progressive irrespective of the scoring method used. In early disease,
      the SRM was significantly larger for the SHS and Kellgren scores compared with
      the Sharp Max score. In late disease, the Kellgren score was slightly more
      sensitive to change compared with the SHS and Sharp Max scores; the difference,
      however, did not reach significance. In erosive disease, the SRM was
      significantly larger for the Kellgren compared with the SHS and Sharp Max scores.
      The numbers of patients needed to detect a 50% difference during the 0-3-year
      followup period were 129, 138, and 124 for the SHS, the Sharp Max, and the
      Kellgren, respectively. The numbers of patients needed to detect a 50% difference
      during the 6-12-year followup period were 117, 121, and 104, respectively. The
      numbers of patients needed to detect a 50% difference during the 6-12-year
      followup in patients with erosive disease were 74, 78, and 68, respectively, for
      the 3 scores. The Kellgren required 33 minutes to score 10 sets of radiographs of
      the hands and feet; the SHS score took 55 minutes. CONCLUSION: The Kellgren
      scoring system is the most efficient method for monitoring the radiologic
      progression of RA. The Kellgren and the SHS are equally sensitive to change early
      in the disease, whereas the Kellgren score becomes more sensitive to change late
      in the disease in patients with erosions.

PMID- 10902746
TI  - Adjacent genes, for COL2A1 and the vitamin D receptor, are associated with
      separate features of radiographic osteoarthritis of the knee.
AB  - OBJECTIVE: To study the association of the COL2A1 genotype, in relation to the
      vitamin D receptor (VDR) genotype, with features of radiographic osteoarthritis
      (ROA) in a population of elderly men and women. METHODS: In this cross-sectional
      study, we analyzed a population-based sample of 851 men and women ages 55-80
      years from a large cohort study, the Rotterdam Study. We determined the
      prevalence of ROA of the knee according to the Kellgren/Lawrence (K/L) score and
      features of ROA (presence of osteophytes and narrowing of the joint space [JSN])
      without considering clinical parameters of the disease. Genotypes were determined
      at a variable-number tandem repeats marker 1 kb downstream of the COL2A1 gene
      using a newly developed heteroduplexing method. The VDR genotype was previously
      determined by a direct molecular haplotyping polymerase chain reaction method to
      establish the phase of alleles at 3 adjacent restriction fragment length
      polymorphisms for Bsm I, Apa I, and Taq I. RESULTS: We found the COL2A1 genotype
      to be associated with a 2-fold increased risk for JSN, but not with osteophytes
      or the K/L score. We had previously found the VDR genotype to be associated with
      osteophytes and the K/L score, but not with JSN. When the COL2A1 genotype was
      analyzed in combination with the VDR genotype, we found evidence suggesting that
      the presence of haplotypes of the 2 genes was associated with increased risk for
      ROA. CONCLUSION: Our findings demonstrate that both the COL2A1 gene and the VDR
      gene are involved in ROA, but in separate features. The COL2A1 genotype is
      associated with JSN, while the VDR genotype is associated with osteophytes.

PMID- 10902748
TI  - Relationship between time-integrated C-reactive protein levels and radiologic
      progression in patients with rheumatoid arthritis.
AB  - OBJECTIVE: An elevated acute-phase response is associated with increased
      radiologic damage in rheumatoid arthritis (RA), but development of damage in
      previously normal joints ("new joint involvement") has not previously been
      investigated. This study was undertaken to investigate the hypothesis that when
      there is suppression of disease activity as judged by the C-reactive protein
      level, new joint involvement is reduced to a greater extent than is progression
      in already damaged joints ("damaged joint progression"). METHODS: Three hundred
      fifty-nine patients with active RA were studied as part of a 5-year randomized,
      prospective, open-label study of disease-modifying antirheumatic drug therapy.
      Time-averaged CRP was calculated from samples obtained every 6 months, and
      patients were divided into groups with CRP values of <6, 6-<12, 12-<25, and > or
      =25 mg/liter. Radiographs of the hands and feet were scored by the Larsen method;
      a damaged joint was defined as one with a score of > or =2. RESULTS: The rank
      correlation between time-integrated CRP and increase in Larsen score was 0.50;
      the correlation increased to 0.59 for patients entering the study with disease
      duration of < or =2 years. The percentage of new joint involvement over 5 years
      varied markedly with time-integrated CRP, from 7.3% in the CRP <6 mg/liter group
      to 39.1% in the CRP > or =25 mg/liter group (5.4-fold increase). The percentage
      of damaged joint progression increased from 26.1% in the CRP <6 mg/liter group to
      41.6% in the CRP > or =25 mg/liter group (1.6-fold increase). CONCLUSION: The
      results of this study provide further confirmation that high CRP levels over time
      are associated with greater radiologic progression. Although radiologic
      progression still occurred in both previously normal and damaged joints despite
      the presence of normal CRP levels, this consisted of proportionately less new
      joint involvement compared with damaged joint progression. These findings support
      the idea that disease-suppressive therapy should be instituted at an early stage
      in patients with RA, before erosive damage has occurred.

PMID- 10902749
TI  - Determining minimally important changes in generic and disease-specific health
      related quality of life questionnaires in clinical trials of rheumatoid
      arthritis.
AB  - OBJECTIVE: To define clinically meaningful changes in 2 widely used health
      related quality of life (HQL) instruments in studies of patients with rheumatoid
      arthritis (RA). METHODS: Patients with RA (n = 693) who were enrolled in 2 double
      blind, placebo-controlled clinical trials completed the Short Form 36 (SF-36)
      modified health survey and the Health Assessment Questionnaire (HAQ) disability
      index at baseline and 6-week followup assessments. Data on 5 RA severity measures
      were also collected at baseline and at 6 weeks (patient and physician global
      assessments, joint swelling and tenderness counts, and global pain assessment).
      Comparison of changes in the SF-36 scales and HAQ scores was made between groups
      of patients known to differ in the level of change on each RA severity measure.
      RESULTS: With few exceptions, changes in the SF-36 and HAQ scores were different
      between patients who differed in the level of change on each RA severity measure.
      Changes in the SF-36 and HAQ scores were more strongly related to changes in the
      patient and physician global assessments and patient pain assessment than to
      changes in the joint swelling and tenderness counts. CONCLUSION: Based on these
      results, minimally important changes in the SF-36 scales and HAQ disability
      scores were determined, which will be useful in interpreting HQL results in
      clinical trials.

PMID- 10902751
TI  - Subtyping of juvenile idiopathic arthritis using latent class analysis. British
      Paediatric Rheumatology Group.
AB  - OBJECTIVE: To use statistical techniques to identify underlying subtypes of
      juvenile idiopathic arthritis (JIA) that best explain the observed relationships
      of clinical and laboratory variables, and to compare the statistically derived
      subtypes with those defined by the International League of Associations for
      Rheumatology (ILAR) criteria and examine them for HLA associations. METHODS:
      Information on 572 patients diagnosed as having JIA was summarized by 10 clinical
      and laboratory categorical variables (age at onset, large joint involvement,
      small joint involvement, polyarthritis, symmetric arthritis, spinal pain, fever,
      psoriasis, antinuclear antibodies [ANA], and rheumatoid factor). Latent class
      analysis (LCA) was used to identify underlying ("latent") classes that explained
      the relationships among the observed variables. Statistical models incorporating
      5-8 latent classes were applied to the data. RESULTS: The 7-class model was the
      most appropriate. Patterns of joint involvement and the presence of ANA were
      influential in determining latent classes. There was some correspondence between
      the latent classes and the ILAR categories, but they did not coincide completely.
      Significant differences between the latent classes were seen for 3 HLA haplotypes
      (DRB1*04-DQA1*03-DQB1*03, DRB1*13-DQA1*01-DQB1*06, and DRB1*08-DQA1*0401
      DQB1*0402). CONCLUSION: LCA provides a novel approach to the task of identifying
      homogeneous subtypes within the umbrella of JIA. In further work, the identified
      latent classes will be examined for associations with other candidate genes and
      for differences in outcome.

PMID- 10902750
TI  - Inhibition of neutrophil migration soon after initiation of treatment with
      leflunomide or methotrexate in patients with rheumatoid arthritis: findings in a
      prospective, randomized, double-blind clinical trial in fifteen patients.
AB  - OBJECTIVE: Leflunomide is a novel immunomodulating drug that has recently been
      approved as a disease-modifying antirheumatic drug for the treatment of
      rheumatoid arthritis (RA). The aim of this study was to determine the
      relationship between the clinical effects of leflunomide and neutrophil
      migration. METHODS: The effects of leflunomide and methotrexate on neutrophil
      chemotaxis were studied in 15 RA patients who participated in a prospective,
      randomized, double-blind clinical trial. When possible, neutrophil numbers were
      counted in synovial fluid (SF) samples at baseline and after 14 days, 4 months,
      and 1 year of treatment. The chemotactic properties of peripheral blood
      neutrophils from RA patients treated with either leflunomide or methotrexate were
      studied by the Boyden chamber technique, using the activators formyl-methionyl
      leucyl-phenylalanine (fMLP) and interleukin-8 (IL-8). The in vitro effects of A77
      1726, the active metabolite of leflunomide, and methotrexate on peripheral blood
      neutrophils from 7 healthy control subjects were also investigated. RESULTS: Both
      therapy groups exhibited clinical improvement, including rapid reductions in SF
      neutrophil counts and reduced joint swelling and tenderness. On day 14, 3 of 7
      patients who received leflunomide showed no detectable effusions. There was a
      significant effect on neutrophil chemotaxis (P < 0.001), which was similar for
      leflunomide and methotrexate. The direct effects on the neutrophils diminished
      over time. Incubation of peripheral blood neutrophils from healthy controls with
      A77 1726 confirmed the inhibitory effect on chemotaxis. CONCLUSION: Leflunomide
      treatment is beneficial in RA patients. Different mechanisms are operative in
      various phases of treatment, leading to decreased recruitment of inflammatory
      cells in the joints.

PMID- 10902752
TI  - Young adults with juvenile arthritis in remission attain normal peak bone mass at
      the lumbar spine and forearm.
AB  - OBJECTIVE: To assess the impact of disease activity on acquired peak bone mass
      and bone turnover in young adult patients with either persistent juvenile
      arthritis (JA) or a history of JA (JA in remission). METHODS: Two hundred twenty
      nine patients with JA were studied after a mean +/- SD of 15.6 +/- 2.4 years in
      women and 14.9 +/- 2.1 years in men since disease onset. One hundred forty-five
      women and 84 men were over the age of 20 at the time of examination (mean +/- SD
      age 24.9 +/- 2.9 years for women and 25.2 +/- 3.1 years for men). Forty-one
      healthy women (mean +/- SD age 27.4 +/- 3.1 years) and 55 healthy men (mean +/-
      SD age 25.7 +/- 3.1 years) served as a reference group. Bone mineral density
      (BMD) was analyzed by dual x-ray absorptiometry. Serum osteocalcin concentrations
      and urinary concentrations of deoxypyridium (D-Pyd) were measured. Linear
      regression analyses were performed to evaluate the impact of disease on BMD.
      RESULTS: Patients with persistent disease had significantly lower BMD compared
      with healthy subjects (P < 0.001 for women at all measured sites and for men at
      the femoral neck and total body; P < 0.05 for men at the radius and lumbar
      spine). Of the patients with a history of JA, only women had significantly lower
      BMD at the femoral neck and total body (P < 0.05). Patients with persistent JA
      had significantly more osteopenia and osteoporosis than healthy subjects, while
      patients with a history of JA had more frequent osteopenia only in the total
      body. Weight, urinary concentration of D-Pyd, and belonging to the patient group
      significantly affected BMD at all measured sites in the entire study population,
      while analysis of all patients found that only the number of months taking
      corticosteroids significantly affected BMD at all measured sites. However, the
      impact of the variables differed from site to site. CONCLUSION: Our findings
      imply that most young adults with JA attain the same BMD as healthy subjects if
      the disease goes into remission, while young adults with active disease have
      increased risk for osteopenia and osteoporosis.

PMID- 10902753
TI  - Natural immune response involving anti-endothelial cell antibodies in normal and
      lupus pregnancy.
AB  - OBJECTIVE: To determine whether immunoglobulins with affinity for the vascular
      endothelium displayed any distinguishing behavior during normal and systemic
      lupus erythematosus (SLE) pregnancy. We also attempted to verify whether isotype
      expression of anti-endothelial cell antibodies (AECA) would have any predictive
      value for pregnancy outcome. METHODS: Sera from 38 pregnant patients with SLE, 68
      normal pregnant women, and 84 nonpregnant healthy controls were studied. IgM- and
      IgG-AECA were determined by cellular enzyme-linked immunosorbent assay using
      fixed cultured human umbilical vein endothelial cells. RESULTS: A significantly
      higher level of IgM-AECA was found during normal pregnancy compared with that in
      healthy nonpregnant controls (mean +/- SD 39 +/- 12% versus 21 +/- 12%; P <
      0.0001). Most pregnant patients with SLE did not have increased titers of IgM
      AECA, but instead had levels similar to those found in healthy nonpregnant
      controls (23 +/- 12%; P not significant). The lowest levels of IgM-AECA in lupus
      pregnancy were associated with preeclampsia (odds ratio 16, P < 0.005).
      Conversely, IgG-AECA levels were significantly higher in the serum of normal
      pregnant women and pregnant SLE patients than in the serum of healthy nonpregnant
      controls (24 +/- 7% and 24 +/- 14% versus 9 +/- 7%; P < 0.0001). CONCLUSION: Our
      results indicate that an active immune response occurs during pregnancy. This
      response involves increased activity of AECA, suggesting a role of autoantibodies
      as a possible contributing factor toward fetal tolerance. Our observations
      further indicate that impaired immune regulation, such as diminished levels of
      serum IgM-AECA detected in SLE patients, might contribute to the impaired
      reproductive function commonly found in SLE.

PMID- 10902754
TI  - Spectrum of autoantibodies against a dynamin-related protein, dymple.
AB  - OBJECTIVE: To characterize the clinical features of patients with autoantibodies
      against dymple, a dynamin-related protein. METHODS: Serum samples from 281
      patients with rheumatic diseases were examined. The characteristics of antidymple
      and antibody-reactive determinants were investigated by immunoblotting with the
      recombinant dymple antigen, including its deletion mutants, and by
      immunofluorescence studies with affinity-purified serum. RESULTS: Five serum
      samples (2%) were found to have antidymple. All of these patients were male, and
      4 of them had interstitial pneumonitis. Their sera were considered to mainly
      recognize the N-terminus of dymple, which contains GTP-binding motifs.
      CONCLUSION: Dymple, which joins the cytoplasmic autoantigens, could be a marker
      for a newly recognized subset of connective tissue diseases.

PMID- 10902755
TI  - Gallium-67 scintigraphy in macrophagic myofasciitis.
AB  - OBJECTIVE: To evaluate gallium-67 (67Ga) uptake and the value of 67Ga
      scintigraphy for diagnosis of macrophagic myofasciitis (MMF), a recently
      identified inflammatory myopathy. METHODS: Twelve consecutive patients with MMF
      confirmed by muscle biopsy, 10 with polymyositis, 10 with sarcoidosis, 8 with
      fibromyalgia, and 10 with lymphoma without muscle symptoms (serving as normal
      controls for muscle) were included. Patients received 1.8 MBq 67Ga per kg body
      weight by intravenous injection, and scintigraphy was performed with a 2-head
      gamma camera. The various views were acquired for the 3 main photopeaks of 67Ga
      48 hours after infusion, and were analyzed in 2 blinded experiments by nuclear
      physicians. A semiquantitative scale was used to compare the uptake of 67Ga in
      the vascular soft tissue background with that in the muscles or joints of MMF
      patients, and with that in the normal controls. RESULTS: The MMF patients (4 men
      and 8 women, mean +/- SD age 47.8 +/- 8.7 years) had chronic myalgia (n = 11;
      predominantly in the lower limbs), asthenia (n = 10), arthralgia (n = 7), mild
      muscle weakness (n = 5), and high serum creatine kinase levels (n = 6). All MMF
      patients had significantly higher levels of 67Ga uptake in the muscle and para
      articular areas than that recorded for the soft tissue background and for the
      controls. Muscle uptake was bilateral, symmetric, and homogeneous, and
      predominantly localized in the legs. No linear enhancement corresponding to
      fascias or synovial involvement was observed. In patients with polymyositis,
      symmetric, but heterogeneous, 67Ga uptake was observed in muscle, but not in the
      fascia. In patients with sarcoidosis, 67Ga uptake was nodular and heterogeneous
      in muscle, was not detected in the fascia, and was suggestive of synovial
      involvement in the joints. The uptake of 67Ga in fibromyalgic patients was
      similar to that in normal controls and to that in the soft tissue background.
      CONCLUSION: MMF is a new condition involving characteristic changes that can be
      detected by deltoid muscle biopsy. It usually manifests as a weakly specific,
      chronic arthromyalgic syndrome that predominates in the lower limbs. 67Ga
      scintigraphy is a noninvasive method that may make it easier to differentiate MMF
      from fibromyalgia and sarcoidosis.

PMID- 10902756
TI  - Modification of disease outcome in Salmonella-infected patients by HLA-B27.
AB  - OBJECTIVE: To study whether HLA-B27 modifies the outcome of Salmonella infection
      in vivo. METHODS: The frequency of HLA-B27 was determined in 198 Salmonella
      infected patients and 100 healthy controls by immunofluorescence and polymerase
      chain reaction. The excretion of Salmonella was monitored at monthly intervals.
      The symptoms of acute infection and possible joint involvement were evaluated
      using questionnaires. RESULTS: Thirty-eight of 198 Salmonella-infected patients
      (19.2%) and 13 of 100 healthy controls (13.0%) were HLA-B27 positive. The
      excretion of Salmonella did not differ significantly between HLA-B27-positive and
      -negative patients, or for patients with versus those without joint symptoms. As
      many as 35 patients (17.7%) reported Salmonella-triggered joint symptoms. Three
      of 14 patients (21.4%) with arthralgia, 5 of 13 patients (38.5%) with probable
      reactive arthritis (ReA), and 6 of 8 patients (75%) with confirmed ReA were HLA
      B27 positive. The duration and severity of joint symptoms directly correlated
      with HLA-B27 positivity. Women reported Salmonella-induced pain and swelling of
      joints more frequently than men (P = 0.07 and P = 0.03, respectively). Patients
      with Salmonella-triggered joint symptoms reported abdominal pain and headache
      more frequently than patients without joint symptoms (P = 0.05 and P = 0.004,
      respectively). CONCLUSION: HLA-B27 did not (at least, not strongly) confer
      susceptibility to Salmonella infection. Salmonella excretion correlated neither
      with HLA-B27 positivity nor with the occurrence of joint symptoms. Joint symptoms
      were surprisingly common during or after Salmonella infection. HLA-B27-positive
      patients had a significantly increased risk of developing joint and tendon
      symptoms. Moreover, HLA-B27 positivity correlated with the development of more
      severe and prolonged joint symptoms.

PMID- 10902758
TI  - Clinical images: Stiff skin syndrome.

PMID- 10902757
TI  - A novel missense mutation (C30S) in the gene encoding tumor necrosis factor
      receptor 1 linked to autosomal-dominant recurrent fever with localized myositis
      in a French family.
AB  - OBJECTIVE: To characterize both phenotypic (clinical features and magnetic
      resonance imaging [MRI] findings) and genotypic aspects of autosomal-dominant
      recurrent fever, also known as tumor necrosis factor receptor (TNFR)-associated
      periodic syndrome (TRAPS), in a French family and to investigate the role of the
      mutated 55-kd tumor necrosis factor alpha (TNFalpha) receptor (TNFR1) in the
      pathogenesis of the disease. METHODS: The coding region of TNFR1 was sequenced in
      2 individuals with TRAPS (the propositus and her grandfather) and in 3 clinically
      unaffected relatives. Expression of soluble TNFR1 (sTNFR1) was investigated in 3
      of the family members carrying a C30S mutation in TNFR1, and was compared with
      the levels of soluble TNFR2 (sTNFR2) by enzyme-linked immunosorbent assay. The
      membrane TNFR1 expression was then compared with membrane TNFR2 levels at the
      surface of peripheral blood mononuclear cells by flow cytometric analysis. The
      clinical heterogeneity in this French family was investigated by searching
      polymorphic variants in the TNFalpha promoter by DNA sequencing. RESULTS: Both
      the disease course and the clinical presentation in the propositus were highly
      indicative of TRAPS. MRI study of the segmental inflammatory process in the limbs
      showed abnormal signals in the muscle and subcutaneous tissue without involvement
      of adjacent joints or fascia. A novel missense mutation, C30S, in the first
      extracellular N-terminal cysteine-rich domain (CRD1) of TNFR1 was characterized
      in the propositus, her affected grandfather, and her clinically unaffected
      father. Expression of membrane TNFR1 at the surface of monocytes and
      polymorphonuclear leukocytes, as well as the levels of sTNFR1 in serum when the
      disease was not active were not modified in the 3 individuals carrying the TNFR1
      C30S mutation. In contrast, during attacks, sTNFR1 levels remained abnormally
      low, as compared with the levels in unrelated patients with active adult-onset
      systemic Still's disease. The clinical heterogeneity could not be explained by a
      polymorphic variant in the TNFalpha promoter. CONCLUSION: TRAPS is a distinct
      clinical and radiologic disease entity that is responsible for recurrent fever
      and migratory cellulitis-like processes with localized myositis. We have
      identified a novel TNFR1 mutation, C30S, that is located in the CRD1 domain in a
      French family affected by the disease. This mutation seems to affect the level of
      sTNFR1, which did not increase in the propositus during inflammatory attacks.

PMID- 10902759
TI  - Detection of Chlamydia pneumoniae in giant cell vasculitis and correlation with
      the topographic arrangement of tissue-infiltrating dendritic cells.
AB  - OBJECTIVE: Recent studies suggest that giant cell arteritis (GCA) may be an
      antigen-driven disease. Since Chlamydia pneumoniae has been identified in
      arterial vessel walls, it was hypothesized that this organism might be associated
      with GCA. METHODS: Fourteen paraffin-embedded temporal artery biopsy specimens
      from 9 patients with GCA were examined by immunohistochemistry and by polymerase
      chain reaction (PCR) for the presence of C pneumoniae; for 5 patients, specimens
      were available from both the left and right arteries. Four temporal artery
      specimens from 3 patients with polymyalgia rheumatica (PMR) and 9 temporal artery
      specimens from 5 patients without GCA or PMR served as controls. RESULTS: C
      pneumoniae was detected by both immunohistochemistry and PCR in 6 GCA patient
      samples. One GCA patient sample was immunopositive only; another was PCR positive
      only. Thus, C pneumoniae was found in 8 of 9 GCA patients. One of 4 control
      samples from the PMR patients was immunopositive, but PCR negative, for C
      pneumoniae. The C pneumoniae-positive PMR patient also had respiratory symptoms.
      The remaining 9 control samples were negative for C pneumoniae by both
      immunohistochemistry and PCR. Immunohistochemistry showed that bacteria
      predominate in the adventitial layer of temporal arteries, in granulomatous
      infiltrates. Dendritic cells were examined by immunohistochemistry for their
      presence and localization in consecutive temporal artery specimens, and showed a
      strong topographic relationship with C pneumoniae. Like the bacterium, dendritic
      cells predominate in the adventitial layer of the arteries. CONCLUSION: C
      pneumoniae was found in temporal artery specimens from most GCA patients, in 1
      specimen from a PMR patient, and in no other control specimens; thus, it may play
      a role in the pathogenesis of the disease. Dendritic cells may represent the
      antigen-presenting cells in this situation.

PMID- 10902760
TI  - Autocrine stimulation by insulin-like growth factor 1 and insulin-like growth
      factor 2 mediates chondrocyte survival in vitro.
AB  - OBJECTIVE: To determine the role of autocrine stimulation by insulin-like growth
      factor 1 (IGF-1) and IGF-2 in mediating chondrocyte survival and to determine
      whether chondrocytes from older individuals are more susceptible to cell death
      when IGF action is blocked. METHODS: Survival was assessed in human and monkey
      chondrocytes cultured in suspension in alginate under serum-free conditions. The
      role of IGFs in mediating survival was determined by treating cultures with
      neutralizing antibodies to IGF-1 and IGF-2, an antibody that blocks the type 1
      IGF receptor, and antisense oligonucleotides to inhibit IGF-1 production.
      Survival was measured in chondrocyte cultures from young and old adult monkeys in
      the presence and absence of the IGF receptor blocking antibody and ceramide to
      induce cell death. RESULTS: Cell survival of >90% was noted when chondrocytes
      were cultured for as long as 107 days in alginate in a supplemented serum-free
      medium. Compared with controls, survival was significantly reduced by treatment
      with neutralizing antibodies to IGF-1 (25% cell death), neutralizing antibodies
      to IGF-2 (18% cell death), antibody to the IGF receptor (45% cell death), and IGF
      1 antisense oligonucleotides (28% cell death). Cell death from inhibition of the
      type 1 IGF receptor was associated with an increase in caspase 3 activity and
      with positive DNA fragmentation, consistent with apoptotic cell death.
      Chondrocytes from old adult monkeys were more susceptible to cell death than were
      those from young adult monkeys when the IGF receptor was blocked and cell death
      was further stimulated by ceramide. CONCLUSION: Autocrine production of IGFs
      helps to maintain chondrocyte survival in vitro and could play a similar role in
      vivo. With aging, chondrocytes may become more susceptible to factors that induce
      cell death.

PMID- 10902761
TI  - Mitochondrial oxidative phosphorylation is a downstream regulator of nitric oxide
      effects on chondrocyte matrix synthesis and mineralization.
AB  - OBJECTIVE: Increased chondrocyte nitric oxide (NO) and peroxynitrite production
      appears to modulate decreased matrix synthesis and increased mineralization in
      osteoarthritis (OA). Because NO inhibits mitochondrial respiration, this study
      was undertaken to directly assess the potential role of chondrocyte mitochondrial
      oxidative phosphorylation (OXPHOS) in matrix synthesis and mineralization.
      METHODS: We studied cultured human articular chondrocytes and immortalized costal
      chondrocytes (TC28 cells). We also assessed the effects of antimycin A and
      oligomycin (inhibitors of mitochondrial complexes III and V, respectively) on
      chondrocyte mitochondrial respiration, ATP synthesis, and inorganic pyrophosphate
      (PPi) generation, and the mineralizing potential of released matrix vesicles
      (MV). RESULTS: Articular chondrocytes and TC28 cells respired at comparable
      rates. Peroxynitrite and NO donors markedly suppressed respiration and ATP
      generation in chondrocytes. Because NO exerts multiple effects on chondrocytes,
      we investigated the primary functions of mitochondrial respiration and OXPHOS. To
      do so, we identified minimally cytotoxic doses of antimycin and oligomycin, which
      both induced intracellular ATP depletion (by 50-80%), attenuated collagen and
      proteoglycan synthesis, and blocked transforming growth factor beta from
      increasing intracellular ATP and elaboration of PPi, a critical inhibitor of
      hydroxyapatite deposition. Antimycin and oligomycin also abrogated the ability of
      the ATP-hydrolyzing enzyme plasma cell membrane glycoprotein 1 (PC-1) to increase
      chondrocyte PPi generation. Finally, MV from cells treated with antimycin or
      oligomycin contained less PPi and precipitated >50% more 45Ca. CONCLUSION:
      Chondrocyte mitochondrial reserve, as NO-sensitive mitochondrial respiration
      mediated ATP production, appears to support matrix synthesis and PPi elaboration
      and to regulate MV composition and mineralizing activity. NO-induced depression
      of chondrocyte respiration could modulate matrix loss and secondary cartilage
      mineralization in OA.

PMID- 10902762
TI  - ATP release by mechanically loaded porcine chondrons in pellet culture.
AB  - OBJECTIVE: To determine whether ATP is released from chondrocytes during
      mechanical stimulation and whether degradation of ATP generates inorganic
      pyrophosphate in chondron pellet cultures. METHODS: Chondron pellets were formed
      from 1.6 x 10(6) cells that had been enzymatically isolated from porcine
      articular cartilage. ATP was measured in media from cultures at rest and during
      fluid movement and cyclic compression. ATP hydrolysis was examined by high
      performance liquid chromatography following the addition of gamma32P-ATP to
      resting cultures. RESULTS: Pellet cultures at rest maintained a steady-state
      concentration of 2-4 nM ATP in 2 ml of medium. The ATP concentration increased 5
      12-fold with cyclic compression (7.5 and 15 kPa at 0.5 Hz), then decreased to
      preloading levels within 60 minutes despite continued loading. A subsequent
      increase in pressure stimulated a further increase in ATP release, suggesting
      that chondrocytes desensitize to load. Cell viability was similar for pellets at
      rest and up to 24 hours after compression. ATP released in response to mechanical
      stimulation was inhibited 50% by 0.5 mM octanol, suggesting a regulated mechanism
      for ATP release. Exogenous ATP was rapidly hydrolyzed to pyrophosphate in resting
      cultures. CONCLUSION: The occurrence of basal levels of extracellular ATP in the
      presence of pyrophosphohydrolase activity indicates that ATP was continuously
      released by chondrocytes at rest. Considering that chondrocytes express
      purinoceptors that respond to ATP, we suggest a role for ATP in extracellular
      signaling by chondrocytes in response to mechanical load. ATP released by
      chondrocytes in response to mechanical load is a likely source of pyrophosphate
      in calcium pyrophosphate dihydrate crystal deposition diseases.

PMID- 10902763
TI  - Response of engineered cartilage tissue to biochemical agents as studied by
      proton magnetic resonance microscopy.
AB  - OBJECTIVE: To test the hypothesis that magnetic resonance imaging (MRI) results
      correlate with the biochemical composition of cartilage matrix and can therefore
      be used to evaluate natural tissue development and the effects of biologic
      interventions. METHODS: Chondrocytes harvested from day-16 chick embryo sterna
      were inoculated into an MRI-compatible hollow-fiber bioreactor. The tissue that
      formed over a period of 2-4 weeks was studied biochemically, histologically, and
      with MRI. Besides natural development, the response of the tissue to
      administration of retinoic acid, interleukin-1beta (IL-1beta), and daily dosing
      with ascorbic acid was studied. RESULTS: Tissue wet and dry weight,
      glycosaminoglycan (GAG) content, and collagen content all increased with
      development time, while tissue hydration decreased. The administration of
      retinoic acid resulted in a significant reduction in tissue wet weight,
      proteoglycan content, and cell number and an increase in hydration as compared
      with controls. Daily dosing with ascorbic acid increased tissue collagen content
      significantly compared with controls, while the administration of IL-1beta
      resulted in increased proteoglycan content. The water proton longitudinal and
      transverse relaxation rates correlated well with GAG and collagen concentrations
      of the matrix as well as with tissue hydration. In contrast, the magnetization
      transfer value for the tissue correlated only with total collagen. Finally, the
      self-diffusion coefficient of water correlated with tissue hydration. CONCLUSION:
      Parameters derived from MR images obtained noninvasively can be used to
      quantitatively assess the composition of cartilage tissue generated in a
      bioreactor. We conclude that MRI is a promising modality for the assessment of
      certain biochemical properties of cartilage in a wide variety of settings.

PMID- 10902764
TI  - Enhanced expression and DNA binding activity of two CCAAT/enhancer-binding
      protein isoforms, C/EBPbeta and C/EBPdelta, in rheumatoid synovium.
AB  - OBJECTIVE: To investigate the activation and expression of CCAAT/enhancer-binding
      proteins (C/EBP), especially C/EBPbeta and -delta, in rheumatoid synovium, and
      their pathogenic implications in rheumatoid arthritis (RA). METHODS: The
      activation of C/EBPbeta and -delta was assessed in synovial tissues from patients
      with RA by electrophoretic mobility shift assay (EMSA); DNA binding activity of
      C/EBPs was evaluated by measuring EMSA band density. The expression and
      distribution of C/EBPbeta and -delta in synovial tissues were examined by
      immunohistochemistry analysis. As a control, synovial tissues from patients with
      osteoarthritis (OA) were studied. RESULTS: Enhanced DNA binding activity of
      C/EBPbeta and -delta, 2 major members of the C/EBP family, was detected in
      synovial tissues from RA patients, while synovial tissues from the patients with
      OA showed only faint or marginal activity (mean +/- SEM arbitrary units [AU] RA
      23.3 +/- 11.7 in RA versus 4.5 +/- 1.3 in OA; P < 0.05). Moreover, the binding
      activities of the C/EBP proteins were correlated with both serum C-reactive
      protein levels (r = 0.62, P < 0.05) and synovial interleukin-6 messenger RNA
      levels (r = 0.60, P < 0.05). In immunohistochemistry studies, C/EBPbeta and 
      delta were detected predominantly in the rheumatoid synovial lining cells (both
      CD14+ and CD14- cells). CONCLUSION: C/EBPbeta and -delta may contribute to the
      pathology of rheumatoid synovitis.

PMID- 10902765
TI  - Expression of osteopontin messenger RNA and protein in rheumatoid arthritis:
      effects of osteopontin on the release of collagenase 1 from articular
      chondrocytes and synovial fibroblasts.
AB  - OBJECTIVE: Osteopontin (OPN) is an extracellular matrix protein that has been
      implicated in the interactions between tumor cells and host matrix, including
      those involved in invasion and spread of tumor cells. Because joint destruction
      in rheumatoid arthritis (RA) is mediated by the invasive growth of synovial
      tissue through its attachment to cartilage, we examined the expression of OPN in
      the synovia of patients with RA and the effect of OPN on the production of
      collagenase 1 in rheumatoid synovial fibroblasts and articular chondrocytes.
      METHODS: The expression of OPN messenger RNA (mRNA) and protein in synovia from
      10 RA patients was examined by in situ hybridization and immunohistochemistry.
      Synovial fibroblasts from RA patients and articular chondrocytes from patients
      without joint disease were cultured in the presence of various concentrations of
      OPN, and levels of collagenase 1 in the culture supernatants were measured by
      enzyme-linked immunosorbent assay. RESULTS: The expression of OPN mRNA and
      protein was observed in 9 of 10 specimens obtained from patients with RA. OPN was
      expressed in the synovial lining and sublining layer and at the interface of
      cartilage and invading synovium. Double labeling revealed that the majority of
      OPN-expressing cells were positive for the fibroblast-specific enzyme prolyl 4
      hydroxylase and negative for the macrophage marker CD68, while only a few, single
      OPN-expressing cells were positive for CD68 at sites of synovial invasion into
      cartilage. OPN staining was not observed in lymphocytic infiltrates or leukocyte
      common antigen (CD45)-positive cells. Three of 3 cultures of human articular
      chondrocytes secreted detectable basal amounts of collagenase, with a dose
      dependent increase upon OPN stimulation, while synovial fibroblast cultures
      produced much lower levels of collagenase, with only 2 of 4 fibroblast cultures
      responding in a dose-dependent manner. CONCLUSION: These findings suggest that
      OPN produced by synovial fibroblasts in the synovial lining layer and at sites of
      cartilage invasion not only mediates attachment of these cells to cartilage, but
      also contributes to matrix degradation in RA by stimulating the secretion of
      collagenase 1 in articular chondrocytes.

PMID- 10902766
TI  - Lack of CD80 expression by fibroblast-like synoviocytes leading to anergy in T
      lymphocytes.
AB  - OBJECTIVE: To investigate whether contact with HLA-DR+, but CD80-, fibroblast
      like synoviocytes (FLS) in the presence of antigen leads to the induction of
      anergy in, rather than stimulation of, T cells. METHODS: Cell surface expression
      of activation and costimulatory markers on FLS were studied by flow cytometry.
      Functional changes were investigated by T cell proliferation to tuberculin
      purified protein derivative or allogeneic responses to FLS, in the presence or
      absence of DAP3.B7 cells, a human CD80-transfected mouse fibroblast cell line.
      Induction of anergy was investigated by a 2-stage culture system. T cells were
      cocultured with allogeneic FLS in the primary culture, rested, and restimulated
      in the secondary culture by FLS in the presence or absence of DAP3.B7 cells or
      interleukin-2 (IL-2). RESULTS: Direct contact between T cells and FLS caused up
      regulation of CD69 on T cells and HLA-DR on FLS in both the allogeneic and
      autologous cultures. The addition of DAP3.B7 cells to FLS-T cell cocultures
      restored the depressed allogeneic responses of T cells. The allogeneic response
      by T cells to FLS in the presence of DAP3.B7 cells could be completely inhibited
      by blocking CD80 with CTLA-4 Ig. Indirect evidence that T cells cocultured with
      FLS were anergic was the up-regulation of CD25, negligible T cell proliferation,
      and the restoration of proliferation by the addition of exogenous IL-2. Direct
      evidence of anergy was obtained when T cells from the primary cultures with FLS
      remained unresponsive to secondary culture with FLS even in the presence of
      DAP3.B7 cells. In contrast, primary culture of T cells with FLS plus DAP3.B7
      cells initiated a good allogeneic response in all subsequent cultures.
      CONCLUSION: It is possible that T cells within the synovium may be anergized by
      contact with HLA-DR+ CD80- FLS.

PMID- 10902767
TI  - Novel in vitro effects of bucillamine: inhibitory effects on proinflammatory
      cytokine production and transendothelial migration of T cells.
AB  - OBJECTIVE: To investigate the novel antiinflammatory mechanism of a disease
      modifying antirheumatic drug, bucillamine, on activated T cells, specifically its
      effect on T cell proliferation, cytokine production, and migration of T cells.
      METHODS: T cells were cultured in wells coated with anti-CD3 monoclonal
      antibodies (mAb) plus anti-CD26 mAb or anti-CD3 plus anti-CD28 mAb, with or
      without bucillamine. Proliferative responses and the production of interleukin-2
      (IL-2), interferon-gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha), IL
      6, IL-4, and IL-5 were measured under these costimulatory conditions.
      Phytohemagglutinin (PHA)-activated T cells were cultured on human umbilical vein
      endothelial cell-coated transwells in the presence or absence of bucillamine, and
      T cells migrating through the endothelial cell layer were counted.
      Immunofluorescence analysis was also performed to analyze the effect of
      bucillamine on the surface expression of adhesion molecules on T cells. RESULTS:
      Bucillamine (64 microM) significantly inhibited T cell proliferation and the
      production of IL-2, IFNgamma, TNFalpha, and IL-6, whereas it had no inhibitory
      effects on the production of IL-4 and IL-5 in the cultures with anti-CD3 plus
      anti-CD26 mAb. In contrast, bucillamine had no effects on T cell proliferation or
      any cytokine production in the cultures with anti-CD3 plus anti-CD28 mAb.
      Furthermore, the same concentration of bucillamine inhibited transendothelial
      migration of PHA-activated T cells, and reduced the expression level of CD44 on T
      cells. CONCLUSION: This study demonstrated the novel effects of bucillamine in
      vitro, showing inhibition of type 1 T helper-type cytokine production and
      proinflammatory cytokine production induced by certain costimulatory conditions,
      and inhibition of transendothelial migration of T cells. The inhibition of T cell
      migration appeared to be mediated partly through the reduced expression of CD44,
      an adhesion molecule on the T cell surface.

PMID- 10902768
TI  - Inhibition of type I collagen gene expression in normal and systemic sclerosis
      fibroblasts by a specific inhibitor of geranylgeranyl transferase I.
AB  - OBJECTIVE: To examine the effects of specific inhibition of geranylgeranyl
      transferase I on the expression of types I and III collagen genes in normal and
      systemic sclerosis (SSc) dermal fibroblasts in vitro. METHODS: Fibroblasts from 2
      normal subjects and 4 SSc patients were incubated with 2-10 microM of GGTI-298, a
      specific geranylgeranyl transferase inhibitor. Type I collagen and fibronectin
      production were determined by enzyme-linked immunosorbent assay. Steady-state
      messenger RNA (mRNA) levels for alpha1(I), alpha2(I), and alpha1(III) collagens
      and fibronectin were assessed by Northern hybridization, and the transcription of
      the alpha1(I) collagen gene was examined by transient transfections with a
      reporter construct containing -5.3 kb of the gene. RESULTS: GGTI-298 caused a
      dose-dependent inhibition of type I collagen production and a reduction in the
      steady-state levels of alpha1(I), alpha2(I), and alpha1(III) mRNA in normal and
      SSc cells. A 60-70% inhibition of type I collagen production and a 70-80%
      reduction in the mRNA levels for alpha1(I), alpha2(I), and alpha1(III) were
      observed at 10 microM GGTI-298. In contrast, the expression of fibronectin,
      cyclooxygenase 1, and GAPDH was not affected. The effects on alpha1(I) collagen
      mRNA resulted from a profound reduction in transcription of the alpha1(I)
      collagen gene promoter. GGTI-298 did not affect cellular viability or morphology.
      CONCLUSION: These results demonstrate that specific inhibition of geranylgeranyl
      prenylation causes a potent and selective inhibition of expression of the genes
      encoding types I and III collagens, without affecting cellular viability. The
      findings indicate that inhibition of geranylgeranyl prenylation should be further
      studied as a potential therapeutic approach for SSc and other fibrosing diseases.

PMID- 10902769
TI  - Distribution of novel polymorphisms of the interleukin-8 and CXC receptor 1 and 2
      genes in systemic sclerosis and cryptogenic fibrosing alveolitis.
AB  - OBJECTIVE: To search for single-nucleotide polymorphisms in the interleukin-8 (IL
      8) and IL-8 receptor CXCR-1 and CXCR-2 genes, and to compare their distribution
      among patients with systemic sclerosis (SSc) with fibrosing alveolitis (FASSc) or
      without fibrosing alveolitis (NFASSc), or patients with cryptogenic fibrosing
      alveolitis (CFA), and normal healthy subjects. METHODS: Fifty control subjects
      were screened for potential polymorphisms by using polymerase chain reaction in
      association with sequence-specific primers incorporating mismatches at the 3'
      end. The novel polymorphisms were subsequently examined in British Caucasian
      subjects, including 194 healthy controls, 71 patients with CFA, and 128 patients
      with SSc who were further subdivided into 78 FASSc patients and 50 NFASSc
      patients. RESULTS: Three novel biallelic polymorphisms were identified in the IL
      8 gene (all in noncoding areas of the gene), 1 was found in the CXCR-1 gene
      (resulting in a conservative amino acid change), and 3 were observed in the CXCR
      2 gene, of which the first resulted in a silent codon change and the others were
      in the 3' untranslated area of exon 3. Compared with controls, a significant
      increase in the frequency of the CXCR-2 +785 CC homozygote and of the CXCR-2
      +1208 TT homozygote was found in the SSc patients (37% versus 22% [P = 0.01] and
      33% versus 17% [P = 0.003], respectively). A subgroup analysis revealed this
      association to be significant both in the FASSc patients and in the NFASSc
      patients. CONCLUSION: This report describes an association between SSc and 2
      polymorphisms occurring close to each other in the CXCR-2 gene. This finding and
      its functional significance need to be confirmed and analyzed in future studies.

PMID- 10902770
TI  - A two-stage, genome-wide screen for susceptibility loci in primary Raynaud's
      phenomenon.
AB  - OBJECTIVE: To identify chromosomal regions containing genes involved in the
      susceptibility to primary Raynaud's phenomenon (RP). METHODS: Six extended
      families with multiple individuals affected with primary RP (n = 37) were
      examined for linkage in a 2-stage, whole-genome screen, using a total of 298
      microsatellite markers. RESULTS: Multipoint, nonparametric linkage analysis
      identified 5 areas of possible linkage, with a nominal level of significance of P
      < or = 0.05. Analysis of a finer map of markers in these regions defined the
      regions of linkage as 21.4 cM on 6q13-6q23.3 (D6S261; P = 0.0004), 10.2 cM on
      7p22-7p15 (D7S664; P = 0.014), 1.6 cM on 9p23-9p22 (D9S156; P = 0.0075), 5.1 cM
      on 17p13.1-17p12 (D17S1791; P = 0.036), and 11.8 cM on Xp11.4-Xp11.23 (DXS8054; P
      = 0.006). Three potential candidate genes map to these regions: the beta subunit
      of the muscle acetylcholine receptor and the serotonin 1B and 1E receptors.
      CONCLUSION: These results provide evidence of the presence and location of genes
      that are involved in the genetic susceptibility to primary RP.

PMID- 10902771
TI  - Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic
      neurotransmission in Sjogren's syndrome.
AB  - OBJECTIVE: Sjogren's syndrome (SS) is an autoimmune disorder characterized by dry
      eyes and mouth (sicca syndrome) and lymphocytic infiltration of the lacrimal and
      salivary glands. Abnormalities of parasympathetic neurotransmission may
      contribute to the glandular dysfunction. In this study, we used a functional
      assay to investigate autoantibody-mediated effects on parasympathetic
      neurotransmission and smooth muscle contraction. METHODS: Serum and purified IgG
      were obtained from patients with primary and secondary SS and from control
      subjects. Contraction of isolated bladder strips in response to stimulation of M3
      muscarinic receptors by a muscarinic receptor agonist, carbachol, or by
      endogenous acetylcholine released from postganglionic parasympathetic nerves was
      measured before and after the addition of patient serum or IgG. RESULTS: Sera
      from 5 of 9 patients with primary SS and from 6 of 6 patients with secondary SS
      inhibited carbachol-evoked bladder contraction by approximately 50%. Sera from
      these patients also inhibited the action of neuronally released acetylcholine at
      M3-muscarinic receptors. Sera from 7 of 8 healthy individuals, from patients with
      rheumatoid arthritis without sicca symptoms, and from patients with systemic
      lupus erythematosus had no effect. The anti-muscarinic receptor activity was
      localized in the IgG fraction, since purified IgG from patients with SS also
      inhibited agonist- and nerve-evoked contractions. In this preliminary study, the
      autoantibodies seemed to be associated with the presence of bladder symptoms and
      other autonomic features. CONCLUSION: Autoantibodies that act as antagonists at
      M3-muscarinic receptors on smooth muscle occur in a subset of patients with
      primary and secondary SS. Their presence in secondary SS was unexpected and
      provides new evidence for a common pathogenetic link between primary and
      secondary SS. These autoantibodies appear to contribute to sicca symptoms and may
      explain associated features of autonomic dysfunction in some patients.

PMID- 10902772
TI  - Clinical images: orbital granuloma and subglottic tracheal stenosis in Wegener's
      granulomatosis.

PMID- 10902773
TI  - An evaluation of an angiotensin-converting enzyme gene polymorphism and the risk
      of arterial thrombosis in patients with the antiphospholipid syndrome.

PMID- 10902774
TI  - Mannose-binding lectin deficiency and infections in homozygous and heterozygous
      patients with systemic lupus erythematosus: comment on the article by Garred et
      al.

PMID- 10902775
TI  - Improvement criteria--clinical and statistical significance: comment on the
      article by Pincus and Stein.

PMID- 10902776
TI  - Pseudogout and intraarticular hyaluronate injections: comment on the article by
      Disla et al.

PMID- 10902777
TI  - Increased MDR1 P-glycoprotein expression in methotrexate resistance: comment on
      the article by Yudoh et al.

PMID- 10902778
TI  - Clinical review 114: hot topic. The role of receptor activator of nuclear factor
      kappaB ligand and osteoprotegerin in the pathogenesis and treatment of metabolic
      bone diseases.

PMID- 10902779
TI  - A monoclonal antibody recognizing the extracellular domain of human Na+/I-
      symporter and its potential applications.

PMID- 10902780
TI  - Failure of membrane targeting causes the functional defect of two mutant sodium
      iodide symporters.
AB  - Molecular cloning of the sodium/iodide symporter (NIS) allowed identification of
      NIS gene mutations in patients with iodide trapping defect. Whereas various
      mutant human (h) NIS molecules display loss of function when expressed by
      transfection in mammalian cells, the precise mechanism(s) responsible for the
      functional abnormality of these proteins remains unknown. With the aim to explore
      these mechanisms in three natural hNIS mutants identified previously in patients
      with iodide trapping defect (Q267E, S515X, and C272X), we have prepared tools
      allowing direct measurement of the protein at its normal location in the plasma
      membrane. A COS-7 cell line was made by transfection that stably expressed high
      levels of wild-type hNIS. It was used to screen by flow cytometry monoclonal
      antibodies (mAbs) prepared from mice immunized against hNIS. Genetic immunization
      was performed by im injection of a wild-type hNIS complementary DNA construct,
      because this procedure has demonstrated the ability to produce antibodies
      recognizing native membrane proteins. One mAb that recognized an epitope of hNIS
      exposed on the extracellular side of the plasma membrane was selected for further
      studies. The epitope was localized on the sixth putative extracellular loop of
      the protein on the basis that the mAb did not recognize rat NIS, which exhibits
      major sequence differences in this segment. When this mAb was used to test by
      flow cytometry the expression of the three mutant hNIS proteins in transfected
      COS-7 cells, it detected similar amounts of wild-type, Q267E, and the S515X hNIS
      molecules in permeabilized cells. In contrast, only the wild-type hNIS was
      detected at the surface of nonpermeabilized cells. The C272X hNIS truncation
      mutant was not detected in intact or permeabilized cells. This is consistent with
      the absence of the mAb epitope from this mutant, which is expected to lack the
      sixth extracellular loop. Our data demonstrate that faulty membrane targeting is
      implicated in the mechanisms causing iodide trapping defect in the Q267E and
      S515X natural hNIS mutants.

PMID- 10902781
TI  - Estrogen suppression in males: metabolic effects.
AB  - We have shown that testosterone (T) deficiency per se is associated with marked
      catabolic effects on protein, calcium metabolism, and body composition in men
      independent of changes in GH or insulin-like growth factor I production. It is
      not clear,,however, whether estrogens have a major role in whole body anabolism
      in males. We investigated the metabolic effects of selective estrogen suppression
      in the male using a potent aromatase inhibitor, Arimidex (Anastrozole). First, a
      dose-response study of 12 males (mean age, 16.1 +/- 0.3 yr) was conducted, and
      blood withdrawn at baseline and after 10 days of oral Arimidex given as two
      different doses (either 0.5 or 1 mg) in random order with a 14-day washout in
      between. A sensitive estradiol (E2) assay showed an approximately 50% decrease in
      E2 concentrations with either of the two doses; hence, a 1-mg dose was selected
      for other studies. Subsequently, eight males (aged 15-22 yr; four adults and four
      late pubertal) had isotopic infusions of [(13)C]leucine and (42)Ca/(44)Ca,
      indirect calorimetry, dual energy x-ray absorptiometry, isokinetic dynamometry,
      and growth factors measurements performed before and after 10 weeks of daily
      doses of Arimidex. Contrary to the effects of T withdrawal, there were no
      significant changes in body composition (body mass index, fat mass, and fat-free
      mass) after estrogen suppression or in rates of protein synthesis or degradation;
      carbohydrate, lipid, or protein oxidation; muscle strength; calcium kinetics; or
      bone growth factors concentrations. However, E2 concentrations decreased 48% (P =
      0.006), with no significant change in mean and peak GH concentrations, but with
      an 18% decrease in plasma insulin-like growth factor I concentrations. There was
      a 58% increase in serum T (P = 0.0001), sex hormone-binding globulin did not
      change, whereas LH and FSH concentrations increased (P < 0.02, both). Serum bone
      markers, osteocalcin and bone alkaline phosphatase concentrations, and rates of
      bone calcium deposition and resorption did not change. In conclusion, these data
      suggest that in the male 1) estrogens do not contribute significantly to the
      changes in body composition and protein synthesis observed with changing androgen
      levels; 2) estrogen is a main regulator of the gonadal-pituitary feedback for the
      gonadotropin axis; and 3) this level of aromatase inhibition does not negatively
      impact either kinetically measured rates of bone calcium turnover or indirect
      markers of bone calcium turnover, at least in the short term. Further studies
      will provide valuable information on whether timed aromatase inhibition can be
      useful in increasing the height potential of pubertal boys with profound growth
      retardation without the confounding negative effects of gonadal androgen
      suppression.

PMID- 10902782
TI  - Visceral adipose tissue is an independent correlate of glucose disposal in older
      obese postmenopausal women.
AB  - Older obese postmenopausal women have an increased risk for type 2 diabetes and
      cardiovascular disease. Increased abdominal obesity may contribute to these
      comorbidities. There is considerable controversy, however, regarding the effects
      of visceral adipose tissue as a singular predictor of insulin resistance compared
      to the other constituents of adiposity. To address this issue, we examined the
      independent association of regional adiposity and total fat mass with glucose
      disposal in obese older postmenopausal women. A secondary objective examined the
      association between glucose disposal with markers of skeletal muscle fat content
      (muscle attenuation) and physical activity levels. We studied 44 healthy obese
      postmenopausal women between 50 and 71 yr of age (mean +/- SD, 56.5 +/- 5.3 yr).
      The rate of glucose disposal was measured using the euglycemic/hyperinsulinemic
      clamp technique. Visceral and sc adipose tissue areas and midthigh muscle
      attenuation were measured from computed tomography. Fat mass and lean body mass
      were estimated from dual energy x-ray absorptiometry. Peak VO2 was measured from
      a treadmill test to volitional fatigue. Physical activity energy expenditure was
      measured from indirect calorimetry and doubly labeled water. Pearson correlations
      indicated that glucose disposal was inversely related to visceral adipose tissue
      area (r = -0.40; P < 0.01), but not to sc adipose tissue area (r = 0.17), total
      fat mass (r = 0.05), midthigh muscle attenuation (r = 0.01), peak VO2 (r = 
      0.22), or physical activity energy expenditure (r = -0.01). The significant
      association persisted after adjusting visceral adipose tissue for fat mass and
      abdominal sc adipose tissue levels (r = -0.45; P < 0.005; in both cases).
      Additional analyses matched two groups of women for fat mass, but with different
      visceral adipose tissue levels. Results showed that obese women with high
      visceral adipose tissue levels (283 +/- 59 vs. 137 +/- 24 cm2; P < 0.0001) had a
      lower glucose disposal per kg lean body mass compared to those with low visceral
      adipose tissue levels (0.44 +/- 0.14 vs. 0.66 +/- 0.28 mmol/kg x min; P < 0.05).
      Visceral adipose tissue is an important and independent predictor of glucose
      disposal, whereas markers of skeletal muscle fat content or physical activity
      exhibit little association in obese postmenopausal women.

PMID- 10902783
TI  - Gender and sexual maturation-dependent contrasts in the neuroregulation of growth
      hormone secretion in prepubertal and late adolescent males and females--a general
      clinical research center-based study.
AB  - Although numerous studies have delineated an impact of gender on the
      neuroendocrine control of GH secretion in the adult, few investigations have
      defined the nature and extent of sex differences before puberty. This deficit
      reflects jointly the sensitivity limitations of earlier GH assays and the paucity
      of intensive sampling protocols in healthy children. Here we have applied a
      chemiluminescence-based GH assay (sensitivity, 0.005 microg/L) to study GH
      release in blood sampled every 10 min for 12 h from 1800-0600 h in 58 healthy
      children. Males and females were evaluated in prepuberty (n = 17 boys; n = 11
      girls) and late adolescence (n = 13 males; n = 17 females). We quantitated the
      principal regulated facets of GH release by 1) deconvolution analysis to assess
      basal vs. pulsatile GH secretion, 2) approximate entropy to compute the
      regularity of GH release patterns, and 3) cosine regression analysis to evaluate
      the overnight rhythmic release of GH. Gender by maturation analysis of variance
      revealed a mean 2.3-fold increase in the integrated serum GH concentration
      between prepuberty and late adolescence (P < 10(-6)). Deconvolution analysis
      disclosed that 91-97% of total GH secretion was pulsatile. Pulsatile, but not
      basal, GH release showed marked sexual maturation dependence (P < 10(-5)).
      Pulsatile GH release rose in adolescents due to a 2.25-fold greater GH secretory
      burst mass (P = 0.00011), which reflected joint 1.5-fold increases in GH
      secretory pulse amplitude and duration (P < 0.01). Pulse-mass enhancement across
      puberty was gender independent, but mechanistically specific, as GH pulse
      frequency, intersecretory burst interval, and half-life were invariant of
      pubertal status. The approximate entropy statistic identified more disorderly GH
      secretion patterns in adolescent females compared with prepubertal children and
      adolescent males (P = 0.00074). Cosinor analysis unmasked elevated overnight
      rhythms in GH secretory burst mass and interburst intervals in late adolescents
      of both genders compared with prepubertal boys (for burst mass) or girls (for
      interburst intervals). Linear regression analysis disclosed strong correlations
      among 1) the plasma insulin-like growth factor I concentration and GH secretory
      burst mass (P < 10(-3)), 2) the GH pulse mass and the serum testosterone
      concentration (P = 10(-3)), 3) the irregularity (entropy) of GH secretory
      patterns and the serum estradiol concentration (P < 10(-4)), and 4) the basal GH
      secretion rate and the serum estradiol concentration (P = 10(-2)). In summary,
      healthy prepubertal children and late adolescent boys and girls manifest
      distinctive mechanisms controlling GH release, as appraised for all three of the
      pulsatile, entropic, and 12-h rhythmic modes of GH neuroregulation. The major
      maturational contrast in the pulsatile mode of GH secretion is amplified
      secretory burst mass in adolescents due to jointly heightened GH pulse amplitude
      and duration. The dominant gender distinction lies in the reduced orderliness of
      GH release patterns in late adolescent girls. Overnight rhythms in GH secretory
      burst mass and interburst intervals enlarge in both sexes at adolescence, thus
      signaling enhanced coupling between the rhythmic and pulsatile control of GH
      release at this time. At the extrema of pubertal development, sex steroid
      hormones are associated differentially with specific facets of GH release, e.g.
      an elevated basal GH secretion rate (estrogen), greater irregularity of GH
      release patterns (estrogen), and amplified GH secretory burst mass and higher
      plasma insulin-like growth factor I concentrations (testosterone). Accordingly,
      we postulate that sex steroids supervise selectively each of the dominant facets
      of GH neurosecretory control across human puberty.

PMID- 10902784
TI  - Pharmacokinetics of a novel testosterone matrix transdermal system in healthy,
      premenopausal women and women infected with the human immunodeficiency virus.
AB  - The clinical consequences of androgen deficiency in human immunodeficiency virus
      (HIV)-infected women remain underappreciated. The pharmacokinetics of
      transdermally administered testosterone in premenopausal women and HIV-infected
      women have not been studied. In this study we compared the pharmacokinetics of a
      novel testosterone matrix transdermal system (TMTDS) in healthy premenopausal
      women and women infected with HIV. Eight menstruating HIV-infected women, 18-50
      yr of age, who had been receiving stable antiretroviral therapy, including a
      protease inhibitor, for at least 12 weeks and nine healthy, menstruating women of
      comparable age were enrolled. After baseline sampling during a 24-h control
      period in the early follicular phase (days 1-6), two TMTDS patches were applied
      with an expected delivery rate of 300 microg testosterone daily over an
      application period of 3-4 days. After 72 h, the patches were removed, a second
      set of two patches was applied, and blood samples were drawn over 96 h. Baseline
      serum total and free testosterone levels were lower in HIV-infected women than in
      healthy women. A diurnal rhythm of testosterone secretion, with higher levels in
      the morning and lower levels in the late afternoon, was apparent in both groups
      of women. Free testosterone levels were in the midnormal range at baseline in
      healthy women and increased above the upper limit of normal during TMTDS
      application. In HIV-infected women, free testosterone levels were in the low
      normal range at baseline and rose into the upper normal range during patch
      application. Serum total testosterone levels increased into the midnormal range
      in HIV-infected women and into the upper normal range in healthy women during
      patch application. The mean increments in free and total testosterone levels were
      significantly lower in HIV-infected women than in healthy women. Testosterone
      bioavailability, expressed as the mean +/- SEM baseline-subtracted area under the
      total testosterone curve, was significantly greater in healthy women than in HIV
      infected women [3323 +/- 566 ng/dL x h (115 +/- 20 nmol/L x h) vs. 1506 +/- 316
      ng/dL x h (52 +/- 11 nmol/ L x h); P = 0.016]. Assuming a daily testosterone
      delivery rate of 300 microg/day, the apparent plasma clearance was significantly
      higher in HIV-infected women than in healthy women (2531 +/- 469 vs. 1127 +/- 217
      L/day1 P = 0.022), respectively. There was no significant change from baseline in
      serum LH, sex hormone-binding globulin, and estradiol levels in either group.
      Serum FSH levels showed a greater decrease from baseline in healthy women. A
      regimen of two testosterone patches applied twice a week can maintain serum total
      and free testosterone levels in the mid- to upper normal range, respectively, in
      HIV-infected women with low testosterone levels. During TMTDS application, the
      increments in serum total and free testosterone levels are lower in HIV-infected
      women than in healthy women, presumably due to increased plasma clearance or
      decreased absorption. Further studies are needed to assess the effects of
      physiological androgen replacement in HIV-infected women.

PMID- 10902785
TI  - Quantitative insulin sensitivity check index: a simple, accurate method for
      assessing insulin sensitivity in humans.
AB  - Insulin resistance plays an important role in the pathophysiology of diabetes and
      is associated with obesity and other cardiovascular risk factors. The "gold
      standard" glucose clamp and minimal model analysis are two established methods
      for determining insulin sensitivity in vivo, but neither is easily implemented in
      large studies. Thus, it is of interest to develop a simple, accurate method for
      assessing insulin sensitivity that is useful for clinical investigations. We
      performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified
      frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15
      type 2 diabetic subjects. We obtained correlations between indexes of insulin
      sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis
      (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a
      sensitivity analysis on our data and discovered that physiological steady state
      values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical
      information about insulin sensitivity. We defined a quantitative insulin
      sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has
      substantially better correlation with SI(Clamp) (r = 0.78) than the correlation
      we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable
      overall correlation between QUICKI and SI(Clamp) in a totally independent group
      of 21 obese and 14 nonobese subjects from another institution. We conclude that
      QUICKI is an index of insulin sensitivity obtained from a fasting blood sample
      that may be useful for clinical research.

PMID- 10902786
TI  - Release of activin and follistatin during cardiovascular procedures is largely
      due to heparin administration.
AB  - Recent evidence has suggested that activin A complexed to its binding protein,
      follistatin, may be present on the surface of cells through their interaction
      with heparan sulfate proteoglycans. As heparin is used routinely in many
      cardiovascular procedures for its anticoagulation properties, it may also cause
      the release of heparin-binding growth factors, including activin and follistatin,
      from the vascular endothelium. We examined the effect of two cardiovascular
      procedures and the use of heparin directly on the circulating concentrations of
      activin A and follistatin. A rapid and robust release of activin A and
      follistatin occurred in the circulation of patients undergoing abdominal aortic
      aneurysm repair or carotid endarterectomy at the time of vessel clamping and
      administration of heparin (5000 IU). This release pattern was dissimilar to that
      of the inflammatory marker, interleukin-1beta. However, administering heparin
      (2500 IU) to coronary angiography patients produced a similar activin and
      follistatin response, whereas placebo-treated angiography patients had no
      response. These findings illustrate that the routine use of heparin in surgical
      procedures elicits a rapid and robust release of activin and follistatin. This
      has direct clinical relevance by potentially activating heparin-binding growth
      factors that are important in injury, hyperplasia, and restenosis of vessels.

PMID- 10902787
TI  - Alterations in nitric oxide/cyclic-GMP pathway in nondiabetic siblings of
      patients with type 2 diabetes.
AB  - In this study, we have compared resistance to insulin-mediated glucose disposal
      and plasma concentrations of nitric oxide (NO) and cyclic-GMP in healthy
      volunteers with (n = 35) or without (n = 27) at least one sibling and one parent
      with type 2 diabetes. The 62 volunteers were further divided into groups of those
      with normal glucose tolerance or impaired glucose tolerance. Insulin-mediated
      glucose disposal was quantified by determining the insulin sensitivity index
      (ISI) in response to a low-dose, constant infusion of insulin (25 mU/kg x h) and
      glucose (4 mg/kg x min) for 150 min. The mean (+/-SEM) ISI [(mL kg(-1) min(
      1)/pmol/L) x 10(3)] was significantly greater in those without a family history
      (30.3 +/- 2.3) as compared with nondiabetic volunteers with a family history of
      type 2 diabetes, whether they had normal glucose tolerance (17.0 +/- 7.2) or
      impaired glucose tolerance (9.5 +/- 1.4). In addition, basal NO levels, evaluated
      by the measurement of its stable end products [i.e. nitrite and nitrate levels
      (NO2-/ NO3-)], were significantly higher, and cyclic-GMP levels, its effector
      messenger, were significantly lower in those with a family history, irrespective
      of their degree of glucose tolerance, when compared with healthy volunteers
      without a family history of type 2 diabetes. Furthermore, when the 62 volunteers
      were analyzed as one group, there was a negative correlation between ISI and NO2
      /NO3- levels (r = -0.35; P < 0.005) and a positive correlation between ISI and
      cyclic-GMP levels (r = 0.30; P < 0.02). These results have shown that alterations
      of the NO/cyclic-GMP pathway seem to be an early event in nondiabetic individuals
      with a family history of type 2 diabetes and these changes are correlated with
      the degree of insulin resistance.

PMID- 10902788
TI  - Transient antiislet autoantibodies: infrequent occurrence and lack of association
      with "genetic" risk factors.
AB  - We hypothesized that genetic determinants of expression of persistent antiislet
      autoantibodies would similarly influence the expression of transient
      autoantibodies. To test this hypothesis, we prospectively evaluated sera from 478
      relatives (SOC: sibling-offspring cohort) of patients with type 1 diabetes as
      well as 793 newborns from the general population (NEC: newborn nonrelative
      cohort) selected for expression of specific human leukocyte antigen haplotypes.
      Eight relatives of 478 (1.7% of SOC) expressed a transient autoantibody, and none
      had the high risk genotype DR3/4(DQ2/8). In contrast, 28 relatives (5.9%) had
      persistent antiislet autoantibodies, and 14 (50%) were DR3/4(DQ2/8)
      heterozygotes. Thirteen children of 793 (1.6% of NEC) expressed a transient
      autoantibody, and none had the high risk genotype DR3/4(DQ2/8). Seven of the NEC
      (0.9%) had persistent antiislet autoantibodies, and 4 (57.1%) were DR3/4(DQ2/8)
      heterozygous. Expression of persistent autoantibodies was strongly related to
      human leukocyte antigen status and family history of type 1 diabetes. In
      contrast, the expression of transient antiislet autoantibodies did not differ by
      family history of diabetes, and none of the DR3/4(DQ2/8) relatives and
      DR3/4(DQ2/8) newborns expressed transient autoantibodies. Our results indicate
      that children can express transient antiislet autoantibodies, but such transient
      autoantibodies are relatively infrequent and are not correlated with known
      genetic risk factors for type 1 diabetes.

PMID- 10902789
TI  - Serum allopregnanolone levels in pregnant women: changes during pregnancy, at
      delivery, and in hypertensive patients.
AB  - Allopregnanolone is a neuroactive steroid measurable in peripheral circulation.
      The aim of the present study was to investigate the presence and the possible
      changes in serum allopregnanolone and progesterone levels in pregnant women
      during gestation, at delivery, and in patients with chronic hypertension, with or
      without superimposed preeclampsia. We also evaluated allopregnanolone in cord
      blood. Three groups of pregnant women were studied: 1) healthy controls followed
      longitudinally throughout gestation (n = 14); 2) at vaginal or cesarean delivery
      (n = 66); and 3) with chronic hypertension (n = 12), with (n = 7) or without (n =
      5) superimposed preeclampsia. Allopregnanolone and progesterone levels were
      measured in maternal and cord serum by RIA. In healthy pregnant women, serum
      allopregnanolone and progesterone levels progressively increased throughout
      gestation. Whereas no changes were found at vaginal delivery, serum
      allopregnanolone and progesterone levels were significantly lower at delivery by
      emergency cesarean section (P < 0.01). Umbilical cord serum allopregnanolone and
      progesterone levels in emergency cesarean were significantly lower than those
      found at vaginal delivery (P < 0.01). Patients with chronic hypertension, with or
      without superimposed severe preeclampsia, showed serum allopregnanolone levels
      significantly higher than those of healthy women at the same gestational age (P <
      0.01). In conclusion, maternal serum allopregnanolone levels increased during
      normal gestation were lower in women who underwent emergency cesarean and higher
      in patients with chronic hypertension, with or without preeclampsia. Because
      allopregnanolone is active on the central nervous system and in the control of
      systemic blood pressure, an involvement of this neurosteroid in the adaptive
      processes induced by pregnancy is suggested.

PMID- 10902790
TI  - A prospective study of the prevalence of the polycystic ovary syndrome in
      unselected Caucasian women from Spain.
AB  - We prospectively estimated the prevalence of the polycystic ovary syndrome
      (PCOS), as defined by the NIH/NICHHD 1990 endocrine criteria, in a population of
      154 Caucasian women of reproductive age reporting spontaneously for blood
      donation. Anthropometric data; the presence of hirsutism, acne, and androgenic
      alopecia; and the menstrual history were recorded by a single investigator. In
      145 women, blood samples were also obtained for measurement of serum androgen
      levels. PCOS was defined by the presence of 1) oligomenorrhea, 2) clinical and/or
      biochemical hyperandrogenism, and 3) exclusion of hyperprolactinemia, thyroid
      disorders, and nonclassic 21-hydroxylase deficiency. Hirsutism was defined by a
      modified Ferriman-Gallwey score of 8 or more, acne was considered as a sign of
      hyperandrogenism when persistent after the second decade of life, and
      hyperandrogenemia was defined by an increase in circulating testosterone or
      dehydroepiandrosterone sulfate or an increase in the free androgen index above
      the 95th percentile of the control values derived from the nonhirsute, nonacneic
      women having regular menses who were not receiving hormonal therapy. PCOS was
      present in 10(6.5%), hirsutism was present in 11 (7.1%), and acne was present in
      19 (12.3%) of the 154 women. Our results demonstrate a 6.5% prevalence of PCOS,
      as defined, in a minimally biased population of Caucasian women from Spain. The
      polycystic ovary syndrome, hirsutism, and acne are common endocrine disorders in
      women.

PMID- 10902791
TI  - Growth hormone therapy of Turner syndrome: the impact of age of estrogen
      replacement on final height. Genentech, Inc., Collaborative Study Group.
AB  - Clinical trials of recombinant human GH therapy in Turner syndrome that began
      more than a decade ago show that GH accelerates the linear growth rate. Several
      studies indicate that final height is also improved, although the magnitude of
      the increase has been debated. The age at which feminization is induced could be
      an important factor in determining the patient's ultimate growth response. To
      test this, 60 patients from a large (n = 117), previously unreported, clinical
      trial of GH treatment were randomly assigned to begin conjugated estrogens at
      either 12 or 15 yr of age. The 60 patients were all less than 11 yr of age at
      entry (mean, 9.5 yr) and received 0.375 mg/kg x week of GH for nearly 6 yr on a
      daily or three times weekly regimen. Height gain was calculated by comparing the
      study patients' final or near final heights to their pretreatment projected
      heights as well as to those of a separate set of age-matched, historical control
      patients. Patients in whom estrogen treatment was delayed until age 15 yr gained
      an average of 8.4 +/- 4.3 cm over their projected height, whereas those starting
      estrogen at 12 yr gained only 5.1 +/- 3.6 cm, on the average (P < 0.01). Analysis
      of the interval data showed that growth was stimulated for approximately 2 yr
      after estrogen initiation, but then declined in association with bone age
      advancement. Patients who were older than 11 yr at entry (n = 57) all initiated
      estrogen 1 yr after beginning GH and showed a mean gain in adult height of 4.7
      cm, similar to those given estrogen at age 12 yr. Multivariate analysis revealed
      that the number of years of GH therapy before estrogen treatment was a strong
      factor in predicting height gained, indicating that the timing of estrogen
      introduction is an important determinant of final height in this cohort of GH
      treated patients with Turner syndrome matched for baseline age and other
      characteristics.

PMID- 10902792
TI  - Subcutaneous adipose tissue metabolism at menopause: importance of body fatness
      and regional fat distribution.
AB  - The aim of this study was to examine the contribution of menopause per se on sc
      adipose tissue (AT) metabolism in 16 women classified on the basis of their
      menopausal status: 8 postmenopausal (mean +/- SD age, 57 +/- 6 yr) vs. 8
      premenopausal individuals (37 +/- 5 yr). These 2 groups were matched for sc
      abdominal adipose cell size (within 0.02 microg lipid/cell) and visceral AT
      accumulation (within 15 cm2), measured by computed tomography. Fasting plasma
      glucose and insulin levels as well as their responses to an oral glucose load
      were similar regardless of the women's hormonal status. Subcutaneous abdominal
      and femoral AT lipoprotein lipase activities as well as fat cell lipolysis were
      determined in both groups. Epinephrine induced antilipolysis at low
      concentrations and lipolysis at higher doses in both adipose sites and groups.
      The maximal lipolytic response to epinephrine or to isoproterenol (beta
      adrenergic agonist) as well as the maximal antilipolytic effect of either the
      catecholamine or UK-14304 (alpha2-adrenergic agonist) assessed in sc adipocytes
      were similar in pre- and postmenopausal women. In addition, neither the beta- nor
      the alpha2-adrenoceptor sensitivity of sc adipose cells differed according to
      subjects' age. Finally, maximal lipolysis promoted by postadrenoceptor agents and
      AT-lipoprotein lipase activity did not vary among adipose regions or between
      groups. Taken together, these results suggest that menopause per se does not
      influence sc AT metabolism once the variation related to adipose cell size and
      total body fatness is taken into account.

PMID- 10902793
TI  - Adipose tissue metabolism in young and middle-aged men after control for total
      body fatness.
AB  - The aim of this study was to compare the sc adipose tissue metabolism of young
      (29 +/- 4 yr) vs. middle-aged men (57 +/- 5 yr), once the concomitant variation
      in total adiposity was taken into account. For this purpose, sc abdominal and
      femoral adipose tissue lipoprotein lipase activities, as well as fat cell
      lipolytic responses, were investigated in 2 groups of 16 men, differing in age
      but displaying similar adipose tissue mass (within 2 kg) and sc abdominal adipose
      tissue area, measured by computed tomography (within 15 cm2). No difference was
      observed in adipose tissue lipoprotein lipase activity of young vs. middle-aged
      subjects, regardless of the adipose region considered. Epinephrine induced
      antilipolysis at low concentrations (10(-9) to 10(-7) mol/L) and a net lipolytic
      response at higher doses (10(-6) to 10(-5) mol/L), regardless of the subjects'
      age and the anatomic location of fat. In addition, the selective alpha2
      adrenergic agonist, UK-14304, promoted a similar antilipolytic response in sc
      abdominal and femoral adipose cells from both groups. However, maximal lipolysis
      induced by isoproterenol (beta-adrenergic agonist) or by postadrenoceptor agents
      such as dibutyryl-cAMP, forskolin, and theophylline were lower in both adipose
      regions of middle-aged (as compared with young) men. No difference in the beta-
      or the alpha2-adrenoceptor sensitivity of sc adipose cells was observed between
      groups. These results indicate that there is, with age, a selective decrease in
      the lipolytic capacity to beta-adrenergic agonist, which seems to be caused by
      postadrenoceptor impairments. Because subjects in the 2 age-groups displayed
      similar body fatness, these alterations are independent from the age-expected
      increase in total adiposity.

PMID- 10902794
TI  - Effects of resistance training and endurance training on insulin sensitivity in
      nonobese, young women: a controlled randomized trial.
AB  - We examined the effects of a 6-month randomized program of endurance training (n
      = 14), resistance training (n = 17), or control conditions (n = 20) on insulin
      sensitivity in nonobese, younger women (18-35 yr). To examine the possible
      mechanism(s) related to alterations in insulin sensitivity, we measured body
      composition, regional adiposity, and skeletal muscle characteristics with
      computed tomography. We observed no changes in total body fat, sc abdominal
      adipose tissue, or visceral adipose tissue with endurance or resistance training.
      Insulin sensitivity, however, increased with endurance training (pre, 421 +/-
      107; post, 490 +/- 133 mg/min; P < 0.05) and resistance training (pre, 382 +/-
      87; post, 417 +/- 89 mg/min; P = 0.06). When the glucose disposal rate was
      expressed per kg fat-free mass (FFM), the improved insulin sensitivity persisted
      in endurance-trained (pre, 10.5 +/- 2.7; post, 12.1 +/- 3.3 mg/min x kg FFM; P <
      0.05), but not in resistance-trained (pre, 9.7 +/- 1.9; post, 10.2 +/- 1.8 mg/min
      x kg FFM; P = NS) women. Muscle attenuation ratios increased (P < 0.05) in both
      endurance- and resistance-trained individuals, but this was not related to
      changes in insulin sensitivity. Moreover, the change in insulin sensitivity was
      not related to the increased maximum aerobic capacity in endurance-trained women
      (r = 0.24; P = NS). We suggest that both endurance and resistance training
      improve glucose disposal, although by different mechanisms, in young women. An
      increase in the amount of FFM from resistance training contributes to increased
      glucose disposal probably from a mass effect, without altering the intrinsic
      capacity of the muscle to respond to insulin. On the other hand, endurance
      training enhances glucose disposal independent of changes in FFM or maximum
      aerobic capacity, suggestive of an intrinsic change in the muscle to metabolize
      glucose. We conclude that enhanced glucose uptake after physical training in
      young women occurs with and without changes in FFM and body composition.

PMID- 10902795
TI  - Molecular analysis of the Pendred's syndrome gene and magnetic resonance imaging
      studies of the inner ear are essential for the diagnosis of true Pendred's
      syndrome.
AB  - Pendred's syndrome is a combination of congenital sensorineural hearing loss and
      iodine organification defect leading to a positive perchlorate test and goiter.
      Although it is the commonest form of syndromic hearing loss, the variable
      clinical presentation contributes to the difficulty in securing a diagnosis. The
      identification of the disease gene (PDS) prompts the need to reevaluate the
      syndrome to identify possible clues for the diagnosis. To this purpose, in three
      Italian families presenting with the clinical features of Pendred's syndrome, the
      molecular analysis was accompanied by full clinical, biochemical, and
      radiological examination. A correlation between genotype and phenotype was found
      in the only patient with enlargement of vestibular aqueduct and endolymphatic
      duct and sac at magnetic resonance imaging. This subject was a compound
      heterozygote for a deletion in PDS exon 10 (1197delT, FS400) and a novel
      insertion in exon 19 (2182-2183insG, Y728X). The present study demonstrates for
      the first time the value of the combination of clinical/radiological and genetic
      studies in the diagnosis of Pendred's syndrome. The positivity of a perchlorate
      discharge test and the malformations of membranous labyrinth fit well with the
      recent achievements on the role of pendrin in thyroid hormonogenesis and the
      maintenance of endolymph homeostasis.

PMID- 10902796
TI  - Long-term follow-up results of postoperative radiotherapy in 36 patients with
      acromegaly.
AB  - In acromegaly, pituitary irradiation is a slow, but effective, intervention in
      decreasing GH concentration. Few studies addressing the outcome of radiotherapy
      have used the currently accepted strict criteria for remission in the analysis of
      data. These studies report a low percentage of remission after radiotherapy.
      Doubt has especially been raised as to whether radiotherapy is effective in
      normalizing serum insulin-like growth factor (IGF)-I concentration. We analyzed
      the long-term follow-up data of postoperatively administered radiotherapy in 36
      patients with postoperative persistent acromegaly, using both the normalization
      of GH suppression during oral glucose loading (GTT) and the normalization of IGF
      I concentration as criteria for remission. Before radiotherapy, mean suppressed
      GH was 9.8 +/- 1.9 mU/L (n = 31), and mean IGF-I concentration was 44.3 +/- 3.9
      nmol/L, equivalent to + 4.76 +/- 0.78 age-related IGF-I SD score (n = 13). The
      median radiation dose was 40 Gray (range, 25-50 Gray). At 5, 10, and 15 yr follow
      up, 18 out of 30 patients (60%), 23 out of 31 patients (74%), and 16 out of 19
      patients (84%), respectively, achieved normal serum IGF-I concentration. At the
      last assessment of all patients, after a mean follow-up period of 139 +/- 12
      months, 27 out of 36 (75%) patients had a normal IGF-I concentration without
      additional medication, whereas 5 patients still required treatment with
      octreotide. Remission, as judged by normalization of GH suppression during GTT,
      was documented in 65% of patients from 2-5 yr after radiotherapy (n = 34); in 69%
      of patients, up to 10 yr after radiotherapy (n = 29); and in 71% of patients, up
      to 15 yr post irradiation (n = 17). At the latest assessment, a mean of 125 +/-
      11 months after radiotherapy, 71% of patients (n = 35) were in remission, as
      defined by normal suppression of serum GH during GTT. Remission, as judged by
      normalization of both GTT and IGF-I, was found in 40% of patients 3-5 yr after
      radiotherapy (n = 30); in 61% of patients, 6-10 yr after radiotherapy (n = 28);
      in 65%, after 11-15 yr after radiotherapy (n = 17); and in 63% of patients, at
      the end of the follow-up period (n = 35). Substitution of one or more pituitary
      hormone deficiencies was required in 11% of patients postoperatively; in 29%, 5
      yr after radiotherapy; in 54%, 10 yr after radiotherapy; and in 58%, more than 15
      yr after radiotherapy. Our findings support the use of radiotherapy as an
      effective intervention in the treatment of residual clinical activity of disease
      after surgery for acromegaly.

PMID- 10902797
TI  - Increased leptin levels in serum and peritoneal fluid of patients with pelvic
      endometriosis.
AB  - Pelvic endometriosis is an immune-related chronic inflammatory disease,
      characterized by ectopic implants of endometrium in the peritoneal cavity and
      associated with increased secretion of proinflammatory cytokines and
      neoangiogenesis. Leptin, the adipocyte-derived hormone, has been shown to have a
      role in food intake, basal metabolism, and reproductive function. Leptin levels
      are dynamically regulated, being elevated by inflammatory mediators and reduced
      by starvation. Leptin itself can influence the proinflammatory immune responses
      of CD4+ T lymphocytes, and reports have also shown this hormone to be an
      angiogenic factor in vitro and in vivo. We investigated whether leptin
      concentrations in serum and peritoneal fluid (PF) differed between 13 patients
      with different stages of endometriosis and 15 age- and body mass index-matched
      controls. We found a statistically significant (P < 0.05) increase in leptin
      levels in serum (30.3 +/- 14.8 ng/mL) and PF (35.9 +/- 17.4 ng/mL) of patients
      with endometriosis, compared with our control population (serum, 15.6 +/- 8.4;
      PF, 17.5 +/- 7.2 ng/mL). Regression equations, relating leptin to body mass
      index, were also significantly different in endometriosis patients, compared with
      controls. Higher levels of leptin were observed in the earlier stages of
      endometriosis than advanced-stage disease. These data suggest that the
      proinflammatory and neoangiogenic actions of leptin may contribute to the
      pathogenesis of endometriosis.

PMID- 10902798
TI  - Serum prostate-specific antigen concentrations are not useful for monitoring the
      treatment of hirsutism with oral contraceptive pills.
AB  - Prostate-specific antigen (PSA) is produced in several female tissues, under the
      regulation of steroid hormones. Serum PSA levels are increased in women with
      hirsutism, and they correlate with serum androgen levels. Therefore, as a marker
      of androgen excess, measurement of serum PSA may play a role in monitoring the
      treatment of hirsutism with contraceptive pills. Sixteen hirsute patients were
      included in the study. Clinical and biochemical variables, including serum PSA
      (using an ultrasensitive chemiluminescent immunoassay), total testosterone, sex
      hormone-binding globulin, androstenedione, dehydroepiandrosterone-sulfate,
      estradiol, and gonadotropin concentrations were recorded at baseline and after 3
      and 6 cycles of treatment with a monophasic contraceptive pill containing
      ethynylestradiol and desogestrel. Twenty-seven healthy women served as controls
      for serum PSA level and for the serum androgen profile. Serum PSA levels were
      higher in hirsute patients, as compared with healthy women (mean +/- SEM: 0.014
      +/- 0.003 vs. 0.006 +/- 0.001 microg/L, P < 0.02). Despite a marked decrease in
      serum androgens (total testosterone and androstenedione, calculated free
      testosterone and free androgen index; and dehydroepiandrosterone-sulfate) and in
      the hirsutism score, and a marked increase in sex hormone-binding globulin
      levels, serum PSA levels did not change and remained detectable in all the
      hirsute patients after 3 and 6 cycles of treatment with contraceptive pills. In
      conclusion, the increased serum PSA levels present in hirsute patients do not
      change during treatment with contraceptive pills and do not parallel the
      amelioration in hirsutism and the decrease in serum androgen concentrations that
      occur during this treatment. Thus, serum PSA measurements have no apparent role
      in the management of hirsute patients on oral contraceptive treatment, at least
      with the ultrasensitive assays currently available.

PMID- 10902799
TI  - Management of the solitary thyroid nodule: results of a North American survey.
AB  - The present survey evaluated current trends in the management of the nontoxic
      solitary thyroid nodule by expert endocrinologists in North America and compared
      their results with a similar European Thyroid Association survey. A questionnaire
      was circulated to all clinical members of the American Thyroid Association. An
      index case (a 42-yr-old woman with a solitary 2 x 3-cm thyroid nodule and no
      clinical suspicion of malignancy) and 11 variations were provided to evaluate how
      each alteration would affect management. One hundred and seventy-eight members
      replied and 142 responses were retained for analysis, corresponding to a response
      rate of 43% of clinically active members. Based on the index case, basal serum
      TSH was the routine choice of 99%, and serum T4 and/or free T4 were included by
      61% of the respondents. Thyroid peroxidase antibodies and serum calcitonin were
      included by 30% and 5%, respectively. Thyroid scintigraphy was used by 23%
      ((123)I, 63%; (99m)Tc, 31%; (131)I, 6%), and ultrasonography was used by 34%.
      Fine needle aspiration biopsy was routinely used by all and was guided by
      palpation in 87%. Based on the individually chosen diagnostic tests indicating a
      benign solitary thyroid nodule in a euthyroid subject, L-T4 treatment was
      advocated by 47%, no specific treatment and follow-up was advocated by 52%, and
      surgery was advocated by 1%. Clinical factors suggesting thyroid malignancy (e.g.
      rapid nodule growth and a large nodule of 5 cm) lead a significant number of
      clinicians (40 - 50%; P < 0.00001) to disregard biopsy results and to choose a
      surgical strategy. Nevertheless, North American endocrinologists heavily rely on
      fine needle aspiration biopsy results. Compared to the European Thyroid
      Association survey, North American endocrinologists use imaging [scintigraphy,
      23% vs. 66% (P < 0.0001); ultrasonography, 34% vs. 80% (P < 0.0001)] and serum
      calcitonin (5% vs. 43%; P < 0.0001) less frequently. A nonsurgical strategy
      prevails in North America, and despite controversies on the effect of L-T4, this
      treatment is supported by more than 40% in both Europe and North America.

PMID- 10902800
TI  - Plamsa leptin response to acute fasting and refeeding in untreated women with
      bulimia nervosa.
AB  - Leptin is known to regulate body weight, energy balance, and reproduction.
      Therefore, investigation of its physiology is of obvious interest in bulimia
      nervosa (BN), an eating disorder characterized by body weight-related
      psychopathology, acute changes in the energy balance, and reproductive
      alterations. To date, the few studies that have assessed leptin production in BN
      have had several limitations, including the measurement of blood leptin levels in
      treated patients and the lack of normal weight healthy controls, so that the
      information they provide is not conclusive. As the investigation of leptin
      dynamics is likely to be more informative, we decided to assess leptin response
      to acute fasting and refeeding in both untreated patients with BN and healthy
      controls. Twelve women meeting the diagnostic criteria for BN of the Diagnostic
      and Statistical Manual of Mental Disorders, and 10 healthy women of the same age
      range participated in a 3-day study. At 1800 h on day 1, they received a meal of
      1088 Cal, with 53% carbohydrates, 17% protein, and 30% fat. Then, they fasted
      until 1800 h on day 2, when they received the same meal. On day 3, they received
      a standard hospital diet of 2600 Cal, divided into 3 meals, with the same
      percentages of nutrients as described above. Blood samples were collected at
      different time points for plasma leptin, glucose, and insulin measurements. In
      bulimic patients, plasma leptin values were significantly lower than in healthy
      women (P < 0.0001) and were positively related to body weight, expressed as body
      mass index (r = 0.86; P < 0.0001). The leptin response to the fasting/refeeding
      paradigm significantly differed between patients and controls (time x group
      interaction, P < 0.0001). In fact, in healthy subjects, acute fasting induced a
      58% decline in the plasma leptin concentration, whereas such a decrease was only
      7% in bulimic women (P < 0.001). After acute refeeding, plasma leptin increased
      in both groups, although in the patients it did not reach the absolute values
      observed in normal controls. No significant difference was observed between
      bulimics and controls in plasma insulin response to the fasting/refeeding
      paradigm, whereas an abnormal increase in blood glucose levels was observed in
      the patients after the first meal following acute fasting. We conclude that in
      untreated women with BN, leptin, despite its very low plasma values, still holds
      its function as a sensor of body weight changes, but loses its role of signaling
      acute changes in energy balance.

PMID- 10902801
TI  - Minimal-model estimates of insulin sensitivity are insensitive to errors in
      glucose effectiveness.
AB  - The minimal-model method allows for estimation of insulin sensitivity (S(I) =
      P(3)/P(2)) and glucose effectiveness (S(G) = P(1)) from the time course of
      glucose and insulin after a glucose bolus. We previously demonstrated that the
      minimal-model results in overestimates of S(G) in subjects with normal insulin
      secretory function. To determine whether overestimation of S(G) has an impact on
      estimation of S(I), we examined model estimation of S(I) when S(G) was
      constrained to levels below that found by the regular minimal-model fit. Fifty
      six glucose tolerance tests from lean and obese women, with and without
      polycystic ovary syndrome, were used. S(I) ranged from 0.2-22.6 x 10(-4) min(
      1)/(microU/mL), and S(G) ranged from 0.8-3.8 x 10(-2) min(-1) for the standard
      minimal-model fits. Constraining S(G) to as low as 40% of the unconstrained value
      resulted in a 4-fold increase in P2 and P3, but only a 3% reduction in S(I). We
      conclude that estimation of the insulin sensitivity index is independent of
      errors in minimal-model-derived estimates of glucose effectiveness.

PMID- 10902802
TI  - Effect of puberty on the relationship between circulating leptin and body
      composition.
AB  - Circulating concentrations of leptin are better correlated with absolute amounts
      of adipose tissue [fat mass (FM)] than with relative body fatness (body mass
      index or percent body fat). There is a clear sexual dimorphism in circulating
      concentrations of leptin (females > males) at birth and in adulthood. However,
      whether such dimorphism is present in the interval between these periods of
      development remains controversial. We examined body composition and clinical
      (Tanner stage) and endocrine (pituitary-gonadal axis hormones) aspects of sexual
      maturation in relationship to circulating concentrations of leptin in 102
      children (53 males and 49 females, 6-19 yr of age) to evaluate the relationship
      between circulating leptin concentrations and body composition before and during
      puberty. Pubertal stage was assigned by physical examination (Tanner staging) and
      also assessed by measurement of plasma estradiol, testosterone, and pituitary
      gonadotropins. Body composition was determined by dual-energy x-ray
      absorptiometry and by anthropometry. Circulating concentrations of leptin in the
      postabsorptive state were determined by a solid-phase sandwich enzyme
      immunoassay. The effect of gender on the relationship between circulating leptin
      concentrations and FM was determined by ANOVA at each Tanner stage. Stepwise
      multiple linear regression analyses, including circulating concentrations of
      pituitary-gonadal axis hormones, and FM were performed, by gender, to determine
      whether the relationship between circulating concentrations of leptin and FM
      changes during puberty. Plasma leptin concentrations were significantly
      correlated with FM at all Tanner stages in males and females. Plasma leptin
      concentrations, normalized to FM, were significantly higher in females than males
      at Tanner stages IV and V but not at earlier stages of pubertal development.
      Plasma leptin concentrations, normalized to FM, were significantly greater in
      females at Tanner stage V compared with females at Tanner stage I and
      significantly lower in males at Tanner stage IV and V compared with males at
      Tanner stage I. These significant gender and maturational differences were
      confirmed by demonstrating that the regression equation relating circulating
      leptin concentrations to FM in females and males at Tanner stages IV and V were
      significantly different (predicted lower leptin concentrations in males than
      females with identical body composition) and that the regression equations
      relating circulating concentrations of leptin to FM in each gender before puberty
      (Tanner stage I) were significantly different (predicted higher plasma
      concentrations of leptin in prepubertal males and lower leptin concentrations in
      prepubertal females) than the same regression equations in later puberty.
      Circulating concentrations of testosterone were significant negative correlates
      of circulating concentrations of leptin normalized to FM in males when considered
      as a group over all pubertal stages. The inclusion in multivariate regression
      analyses of circulating concentrations of testosterone and estradiol, FM, fat
      free mass, and gender did not eliminate a significant gender-effect (P < 0.05) on
      circulating concentrations of leptin at Tanner stages IV and V. The circulating
      concentration of leptin, normalized to FM, declines significantly in males and
      rises significantly in females late in puberty to produce a late-pubertal/adult
      sexual dimorphism. These studies confirm a potent role for gonadal steroids as
      mediators of this sexual dimorphism in circulating concentrations of leptin.
      (ABSTRACT TRUNCATED)

PMID- 10902803
TI  - Steroidogenic enzyme gene expression in the human heart.
AB  - Corticosteroids have specific effects on cardiac structure and function mediated
      by mineralocorticoid (MR) and glucocorticoid (GR) receptors. Aldosterone and
      corticosterone are synthesized in the rat heart. To see whether they might also
      be synthesized in the human cardiovascular system, we examined the expression of
      genes for steroidogenic enzymes as well as genes for GR, MR, and 11
      hydroxysteroid dehydrogenase (11-HSD2; which maintains the specificity of MR).
      Human samples were from left and right atria, left and right ventricles, aorta,
      apex, intraventricular septum, and atrioventricular node as well as whole adult
      and fetal heart. Using RT-PCR, messenger ribonucleic acids encoding cholesterol
      side-chain cleavage enzyme (CYP11A), 3beta-HSD2, 21-hydroxylase (CYP21), 11beta
      hydroxylase (CYP11B1), GR, MR, and 11-HSD2 were detected in all samples with the
      exception of the ventricles, which did not express CYP11B1. Aldosterone synthase
      (CYP11B2) messenger ribonucleic acid was detected in the aorta and fetal heart,
      but not in any region of the adult heart, and 17alpha-hydroxylase (CYP17) was not
      detected in any cardiac sample. Levels of steroidogenic enzyme gene expression
      were typically 0.1% those in the adrenal gland. These findings are consistent
      with autocrine or paracrine roles for corticosterone and deoxycorticosterone, but
      not cortisol or aldosterone, in the normal adult human heart.

PMID- 10902804
TI  - Dysregulated expression of ebaf, a novel molecular defect in the endometria of
      patients with infertility.
AB  - We recently described the expression of ebaf, a novel member of the transforming
      growth factor-beta superfamily in human endometrium. ebaf messenger ribonucleic
      acid was expressed in late secretory and menstrual endometria. Here, we show that
      ebaf is secreted as 42-, 34-, 28-, and 14-kDa proteins into the conditioned
      medium of transfected cells, endometrial fluid, and serum. The amount of secreted
      proteins was markedly reduced during the implantation window in the endometria
      and sera of normal fertile subjects. The expression of ebaf was dysregulated in
      the endometria of a subset of women with infertility during the receptive phase
      of the menstrual cycle. Abundant secreted protein was present in the endometria
      of these women during the implantation window. During the critical period of
      endometrial receptivity, ebaf protein was more abundant in patients with
      endometriosis who did not conceive than in patients who became pregnant. These
      findings show that ebaf is a secreted product and is released into body fluids.
      Some types of infertility are associated with dysregulated expression of ebaf in
      human endometrium, suggesting that a molecular defect in uterine receptivity may
      be identified using such a marker protein.

PMID- 10902805
TI  - Expression of the pituitary transcription factor Ptx-1, but not that of the trans
      activating factor prop-1, is reduced in human corticotroph adenomas and is
      associated with decreased alpha-subunit secretion.
AB  - We have studied the expression of the pituitary transcription factors Ptx-1 and
      Prop-1 in a series of 34 pituitary adenomas fully characterized for in vitro
      hormone secretion and histological staining. In studies involving mammalian cell
      lines, the pituitary transcription factor Ptx-1 has been shown to be a pituitary
      hormone panactivator, whereas more recent studies have shown that it plays an
      important role in alpha-subunit gene expression. Its expression has not been
      examined previously in human pituitary adenomas characterized by in vitro hormone
      secretory profiles. Of the 34 pituitary adenomas studied, Ptx-1 expression was
      reduced by more than 50% compared to that of the housekeeping gene human
      glyceraldehyde-3-phosphate dehydrogenase in the 6 corticotroph adenomas, which
      also had significantly reduced alpha-subunit production (all 6 tumors secreting <
      or =0.5 ng/24 h). Mutations of the pituitary transcription factor Prop-1, which
      is responsible for the syndrome of Ames dwarfism in mice, are being increasingly
      recognized as a cause of combined pituitary hormone deficiency in humans,
      although ACTH deficiency has been described only once. Prop-1 expression was
      detected in all 34 pituitary adenomas, including 6 corticotroph adenomas and 5
      gonadotroph adenomas. The expression of Prop-1 has not been described previously
      in these cell phenotypes.

PMID- 10902806
TI  - Identification of a 25-hydroxyvitamin D3 1alpha-hydroxylase gene transcription
      product in cultures of human syncytiotrophoblast cells.
AB  - Although accumulating data show that placenta is able to synthesize 1,25
      dihydroxyvitamin D3, the presence of cytochrome P(450) enzyme capable of
      converting 25-hydroxyvitamin D3 (250HD(3)) to the biologically active form of
      vitamin D in this tissue, has not been yet clearly established. In this study, we
      have investigated the presence of 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha
      (OH)ase) gene expression products in cultured human syncytiotrophoblast. Total
      RNA was isolated from cultured placental cells and subjected to Northern blots or
      RT-PCR by using 1alpha-(OH)ase-specific primers. The amplified complementary DNA
      fragments were analyzed by gel electrophoresis and nucleotide sequencing. Total
      RNA from kidney HEK 293 cells was subjected to reverse transcriptase reaction,
      and a 298-bp complementary DNA 1alpha-(OH)ase probe was generated by PCR. Primary
      cultures of human syncytiotrophoblasts exhibited 1alpha-(OH)ase activity, and a
      transcript for this gene could be demonstrated in these cells. Northern blot
      analysis revealed the presence of a 2.5-kb product, similar in size to that
      previously reported in kidney. RT-PCR analysis demonstrated the presence of a
      single transcript with nucleotide sequence identical to that previously reported
      for human 1alpha-(OH)ase complementary DNA clones. In addition, data are
      presented which suggest that differentiation of cytotrophoblast to the syncytial
      state was not necessary for this gene to be expressed, which may indicate a role
      of this enzyme all through pregnancy. The overall results of this study provide
      evidence for the presence of 1alpha-(OH)ase in the human placenta, suggesting
      that conversion of 25OHD(3) to 1,25-dihydroxyvitamin D3 in the trophoblast is
      most probably attributed to an enzymatic 1alpha-hydroxylation reaction.

PMID- 10902807
TI  - Retinoids stimulate leptin synthesis and secretion in human syncytiotrophoblast.
AB  - The syncytiotrophoblast (ST), which forms the outer layer of the chorionic villi,
      is the endocrine unit of the human placenta. Bathing in the maternal blood of the
      intervillous space, the ST secretes its hormonal products directly into the
      maternal circulation. Leptin is expressed in the ST and is secreted into the
      maternal circulation. However, its regulation and physiological role during
      pregnancy remain poorly known. In the present work we used the in vitro model of
      human cytotrophoblast differentiation into ST to study the effect of
      physiological and synthetic retinoids on leptin synthesis and secretion. Using
      specific antibodies we first illustrated by immunocytochemistry the expression of
      retinoic acid (RA) receptor alpha and retinoid X receptor alpha (RXRalpha) in ST.
      We then observed that leptin messenger ribonucleic acid and protein expression
      increased with in vitro ST formation. The 9-cis isomer of RA and the synthetic
      retinoid specific for RXRs (BMS 649) stimulated leptin messenger ribonucleic acid
      expression and secretion. In contrast, all-trans-RA and a RA alpha-specific
      ligand had no effect. These results suggest that retinoids regulate leptin
      expression and highlight a role for RXRalpha in this process.

PMID- 10902808
TI  - Activity of the hypothalamic-pituitary-adrenal axis is altered by aging and
      exposure to social stress in female rhesus monkeys.
AB  - Age-related changes in glucocorticoid negative feedback inhibition of
      hypothalamic CRF and pituitary ACTH are observed in rodents. Attempts to study
      similar effects in humans have produced mixed results due in part to the
      difficulty in matching older subjects on social and lifestyle variables. The
      present study used female rhesus monkeys as a model for women by comparing young
      adult (n = 20) to old (n = 20) females to test the hypotheses that the
      hypothalamic-pituitary-adrenal axis is altered in older animals and that this
      difference is exacerbated by exposure to social stress. The effects of age on the
      response to two doses of dexamethasone and two doses of CRF were assessed in
      females living in a stable social environment (control) and in socially stressed
      females removed from their group and housed temporarily in a remote, nonsocial
      environment (separated). The suppression of serum cortisol was not different
      between the two doses of dexamethasone. Before dexamethasone administration (2100
      h), serum cortisol was significantly higher in old control females than in either
      young or old separated females, who were not different from one another. The
      young control females had baseline cortisol concentrations significantly lower
      than all other groups. Serum cortisol was suppressed approximately 75% below
      baseline values in all groups by 10 h after dexamethasone administration. Age
      significantly affected serum cortisol after dexamethasone, as the old control
      group showed a release from suppression 19 h posttreatment compared to the young
      control group and compared to the separated groups. Social condition had a
      significant effect on the responses of serum cortisol and plasma ACTH to CRF
      administration. At baseline (0930 h), serum cortisol was significantly higher in
      young controls compared with older controls, with both separated groups having
      intermediate values. Similarly, plasma ACTH at baseline was significantly higher
      in young controls compared to all other groups. Social separation significantly
      diminished the elevation of both serum cortisol and ACTH after stimulation with
      either dose of CRF. Control females showed a prolonged increase in plasma ACTH
      through 60 min and an increase in serum cortisol through 120 min after CRF. In
      contrast, these hormones either declined by 60 min or did not increase in
      socially separated females after CRF administration. These data suggest that the
      circadian rhythm in serum cortisol may be affected by aging, as levels were
      higher in the evening and lower in the morning in old control compared to young
      control females. The effect of age on the response to dexamethasone treatment
      among the control groups lends support to the hypothesis that the sensitivity of
      glucocorticoid negative feedback diminishes with aging. Although age did not
      affect the response to CRF, social separation diminished the elevation in both
      serum cortisol and plasma ACTH. Whether this effect was due to stress-induced
      down-regulation of pituitary CRF receptors remains to be determined.

PMID- 10902809
TI  - High expression of somatostatin receptors and messenger ribonucleic acid for its
      receptor subtypes in organ-confined and locally advanced human prostate cancers.
AB  - To evaluate the potential application of somatostatin (SST) analogs as an
      adjuvant treatment for prostate cancer, we characterized the binding sites for
      SST octapeptide analogs on prostate cancers in patients treated with radical
      prostatectomy. The affinity and density of binding sites for SST analog RC-160 on
      80 surgical specimens of prostate cancers were determined by ligand competition
      assays. The expression of messenger ribonucleic acid (mRNA) for SST receptor
      subtype 1 (SSTR1), subtype 2 (SSTR2), and subtype 5 (SSTR5) was also investigated
      in 22 samples by RT-PCR. Fifty-two of 80 specimens (65%), showed a single class
      of specific binding sites for RC-160 with a mean dissociation constant (K(d)) of
      9.44 nmol/L and a mean maximal binding capacity of 754.8 fmol/mg membrane
      protein. The mRNA for SSTR1 was detected in 86% of samples, whereas the
      incidences of mRNA for SSTR2 and SSTR5 were 14% and 64%, respectively. The
      expression of SSTR2 and/or SSTR5 was 100%, consistent with the presence of RC-160
      binding. In patients at high risk of cancer recurrence (stage pT3 and/or Gleason
      score of 8-10), the incidence of RC-160 binding (65.7%) was similar to that
      observed in the low risk group (64.3%). The demonstration of the high incidence
      of octapeptide-preferring SSTRs in organ-confined and locally advanced prostate
      cancers supports the merit of further investigations of the application of SST
      analogs and their radionuclide and cytotoxic derivatives for adjuvant treatment
      of patients at high risk of cancer recurrence after radical prostatectomy. Such
      approaches could be also considered for patients with advanced prostate cancer at
      the time of relapse.

PMID- 10902810
TI  - Insulin inhibits the expression of intercellular adhesion molecule-1 by human
      aortic endothelial cells through stimulation of nitric oxide.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial and other
      cell types and participates in inflammation and atherosclerosis. It serves as a
      ligand for leukocyte function-associated antigen-1 on leukocytes and is partially
      responsible for the adhesion of lymphocytes, granulocytes, and monocytes to
      cytokine-stimulated endothelial cells and the subsequent transendothelial
      migration. Its expression on endothelial cells is increased in inflammation and
      atherosclerosis. As it has been suggested that insulin and hyperinsulinemia may
      have a role in atherogenesis, we have now investigated whether insulin has an
      effect on the expression of ICAM-1 on human aortic endothelial cells (HAEC). HAEC
      were prepared from human aortas by collagenase digestion and were grown in
      culture. Insulin (100 and 1000 microU/mL) caused a decrease in the expression of
      ICAM-1 (messenger ribonucleic acid and protein) by these cells in a dose
      dependent manner after incubation for 2 days. This decrease was associated with a
      concomitant increase in endothelial nitric oxide synthase (NOS) expression also
      induced by insulin. To examine whether the insulin-induced inhibition of ICAM-1
      was mediated by nitric oxide (NO) from increased endothelial NOS, HAEC were
      treated with N(omega)-nitro-L-arginine, a NOS inhibitor. N(omega)-Nitro-L
      arginine inhibited the insulin-induced decrease in ICAM-1 expression in HAEC at
      the messenger ribonucleic acid and protein levels. Thus, the inhibitory effect of
      insulin on ICAM-1 expression is mediated by NO. We conclude that insulin reduces
      the expression of the proinflammatory adhesion molecule ICAM-1 through an
      increase in the expression of NOS and NO generation and that insulin may have a
      potential antiinflammatory and antiatherosclerotic effect rather than a
      proatherosclerotic effect.

PMID- 10902811
TI  - Effect of a vitamin D3 analogue on keratinocyte growth factor-induced cell
      proliferation in benign prostate hyperplasia.
AB  - Prostate enlargement and function is under the dual control of androgens and
      intraprostatic growth factors. They regulate, in concert, prostate cell
      proliferation and apoptosis. An increased signaling of both growth factors and
      androgens are supposed to underlie benign prostate hyperplasia (BPH), one of the
      more common disorders of the aging male. Since, in clinical practice, androgen
      ablation resulted in a rather limited decrease in prostate volume, therapeutic
      strategies targeting intraprostatic growth factors are emerging. The activated
      form of vitamin D, vitamin D3, and some of its analogues have been described as
      potent regulators of cell growth and differentiation. In this study, we report
      the effects of one of these vitamin D3 analogues, 1,25-dihydroxy-16ene-23yne D3,
      or analogue (V), on the fate of isolated epithelial cells derived from patients
      with BPH. We essentially found that analogue (V), as well as vitamin D3,
      inhibited BPH cell proliferation and counteracted the mitogenic activity of a
      potent growth factor for BPH cells, such as keratinocyte growth factor (KGF).
      Moreover, analogue (V) induced bcl-2 protein expression, intracellular calcium
      mobilization, and apoptosis in both unstimulated and KGF-stimulated BPH cells.
      Since a short-term (5-min) incubation with analogue (V) reduced the KGF-induced
      tyrosine phosphorylation of a 120-kDA protein, corresponding to the KGF receptor,
      a rapid and direct cross-talk between these two molecules is suggested. Such a
      rapid effect of analogue (V), together with the transient induction of
      intracellular calcium waves, seems to indicate the partial involvement of a
      membrane, nongenomic receptor for vitamin D3. In conclusion, we demonstrated the
      antiproliferative and proapoptotic effect of analogue (V) in BPH cells and
      speculated on its possible use in the therapy of BPH.

PMID- 10902813
TI  - Hypophysiotropic thyrotropin-releasing hormone-synthesizing neurons in the human
      hypothalamus are innervated by neuropeptide Y, agouti-related protein, and alpha
      melanocyte-stimulating hormone.
AB  - We recently demonstrated that three arcuate nucleus-derived peptides,
      neuropeptide Y (NPY), agouti-related protein (AGRP), and alphaMSH, are contained
      in axon terminals that heavily innervate hypophysiotropic TRH neurons in the rat
      brain and may contribute to the altered set-point of the hypothalamo-pituitary
      thyroid axis during fasting. To determine whether a similar regulatory system
      exists in human brain, we performed a series of immunohistochemical studies using
      antisera against NPY, AGRP, alphaMSH, and TRH in adult hypothalami obtained
      within 15 h of death. Numerous small to medium-sized, fusiform and multipolar NPY
      , AGRP-, and alphaMSH-immunoreactive (-IR) cells were widely distributed
      throughout the rostro-caudal extent of the infundibular (arcuate) nucleus. A
      similar distribution pattern was found for NPY- and AGRP-IR neurons in the
      arcuate nucleus, whereas alphaMSH-IR cells appeared to form a separate cell
      population. By double labeling fluorescent immunohistochemistry, 82% of NPY
      neurons cocontained AGRP, and 87% of AGRP neurons coexpressed NPY. No
      colocalization was found between alphaMSH- and AGRP-IR neurons. NPY-, AGRP-, and
      alphaMSH-containing axons densely innervated the hypothalamic paraventricular
      nucleus and were found in close juxtaposition to TRH-synthesizing cell bodies and
      dendrites. These studies demonstrate that in man, the NPY-, AGRP-, and alphaMSH
      IR neuronal systems in the infundibular and paraventricular nuclei are highly
      reminiscent of that observed in the rat and may similarly be involved in
      regulating the hypothalamo-pituitary-thyroid axis in the human brain.

PMID- 10902812
TI  - Effects of menopause and estrogen on cervical epithelial permeability.
AB  - The objective of the study was to characterize the effect and explore the
      mechanisms by which menopause affects paracellular permeability of cultured human
      cervical epithelium. The experimental system was cultures of human ectocervical
      epithelial (hECE) cells on filters. Assays included flux measurements of cell
      impermeable molecules and determinations of transepithelial electrical
      conductance. hECE cells of postmenopausal women formed epithelia with lower
      paracellular permeability than hECE cells of premenopausal women. Treatment with
      estrogen increased paracellular permeability, but levels remained lower compared
      to cultures from premenopausal women. Lowering extracellular calcium or treatment
      with cytochalasin-D, conditions that decrease the tight junctional resistance
      (R(TJ)), increased the permeability, and the relative effects were greater in
      cells of premenopausal women than in postmenopausal women. Treatment of cells
      with sn-1,2-dioctanoyl diglyceride, an agent that increases the R(TJ), decreased
      the permeability, and the relative effect was greater in cells of postmenopausal
      women than in cells of premenopausal women. Estrogen had no significant effect on
      the responses to low calcium, cytochalasin-D, or sn-1,2-dioctanoyl diglyceride.
      Hydrostatic and hypertonic gradients in the subluminal to luminal direction,
      conditions that decrease the resistance of the lateral intercellular space
      increased the permeability to a similar degree in cultures of cells from
      premenopausal and from postmenopausal women. Pretreatment with estrogen augmented
      the increases in permeability in response to hydrostatic and hypertonic
      gradients. In cells exposed to low extracellular calcium, hydrostatic gradients
      had an additive increase in permeability. By extrapolation it was determined that
      in cultures of postmenopausal women R(TJ) contributes 97% to the total
      paracellular resistance, whereas in hECE cultures of premenopausal women the
      R(TJ) contributes only 84%. These results indicate that after menopause the
      transcervical paracellular permeability decreases significantly; this can explain
      the decrease in lubrication of the cervix and vagina in postmenopausal women.
      Part of the effect is due to lack of estrogen, and it can be reversed by
      treatment with the hormone. However, most of the effect is unrelated to estrogen
      and is caused by an increase in R(TJ).

PMID- 10902814
TI  - Localization in tissues and secretion of eotaxin by cells from normal endometrium
      and endometriosis.
AB  - Our laboratories have focused recently on the production and localization of
      eotaxin, a C-C-chemokine of 8.4 kDa, whose major biological activity is the
      chemoattraction of eosinophils. Given evidence of autoimmune activity in the
      endometriosis syndrome, we hypothesized that eosinophil chemoattractants might be
      expressed in endometriosis. In histological sections, we observed eotaxin protein
      localized mainly in epithelial cells, with only very faint immunostaining in the
      surrounding stromal cells. Prominent eotaxin accumulation was noted in the
      luminal epithelium of secretory endometrium. Eotaxin distribution in
      endometriosis was similar to that seen in eutopic endometrium but with higher
      levels of eotaxin staining in the glandular epithelium. Peritoneal fluid
      concentrations of eotaxin were significantly higher in women with moderate or
      severe endometriosis than in women with minimal or mild endometriosis or no
      disease. The treatment of isolated human endometriosis epithelial cells with
      estradiol, medroxyprogesterone acetate, tumor necrosis factor-alpha, and
      interferon-gamma stimulated measurable eotaxin secretion into the conditioned
      media. The results indicate that eotaxin is produced in epithelial cells of
      normal endometrium and endometriosis tissues, varies across the menstrual cycle,
      and is elevated in women with endometriosis. We postulate that eotaxin,
      interacting with other known cytokines and immune cells, contributes to an
      inflammatory reproductive tract environment, leading to endometrial or blastocyst
      dysfunction.

PMID- 10902815
TI  - Autocrine regulation of human preadipocyte migration by plasminogen activator
      inhibitor-1.
AB  - One of the initial stages of adipogenesis is migration of preadipocytes of
      mesenchymal origin into cell clusters to form primitive fat organs. The serine
      protease inhibitor plasminogen activator inhibitor-1 (PAI-1) is synthesized and
      released from human adipose tissue ex vivo and regulates smooth muscle and
      endothelial cell migration in vitro, but its role in adipose tissue is not known.
      We investigated the role of PAI-1 in cultures of human preadipocytes from men and
      women of various ages and body mass indexes. Human preadipocytes expressed the
      messenger ribonucleic acid for PAI-1 and released significant quantities of PAI-1
      protein into the medium. As PAI-1 regulates motility through the interaction of
      vitronectin with its receptor, the integrin alphaVbeta3, we identified this
      receptor in human preadipocytes. Flow cytometric analysis indicated that human
      preadipocytes express the vitronectin receptor alphaVbeta3 in a similar pattern
      as human umbilical vein endothelial cells. Functional studies indicated that
      active, but not latent, PAI-1 inhibited preadipocyte attachment to vitronectin
      with an IC(50) of 13.3 nmol/L, and preincubation of vitronectin-coated Transwells
      with active PAI-1 prevented preadipocyte migration. Vitronectin was identified in
      homogenates of the stromal-vascular fraction of human adipose tissue, but was
      absent from human adipocytes and cultured preadipocytes. These data indicate that
      human preadipocyte migration is regulated through the endogenous expression of
      PAI-1 and alphaVbeta3 integrin, a novel autocrine mechanism for potentially
      regulating cell cluster formation in adipogenesis.

PMID- 10902816
TI  - Expression of menin in parathyroid tumors.
AB  - The multiple endocrine neoplasia type 1 (MEN1) gene seems to be a tumor
      suppressor that encodes a 610-amino acid protein termed menin and that plays an
      important role in the development of MEN1 syndrome. Recent reports indicate that
      heterozygous germline mutations of this gene are responsible for the disease
      onset of MEN1. In this study we examined the expression of menin in parathyroid
      tumors from primary hyperparathyroidism (PHP), secondary hyperparathyroidism
      (SHP), and MEN1 and thyroid tumors including Basedow's disease, thyroid cancer,
      and adrenocortical tumors. Both ribonucleic acid and protein from these tumors
      were applied to RT-PCR and Western blotting, respectively. Primers for RT-PCR
      were designed to amplify the sequence between exons 2 and 3 of the MEN1 gene.
      Specific antibody against menin was generated in guinea pigs immunized with the
      recombinant peptide from amino acid residues 443-535 of menin made by using
      glutathione-S-transferase (GST) gene fusion. Menin messenger ribonucleic acid was
      strongly expressed on RT-PCR analysis in the parathyroid tumors from both PHP and
      SHP. Western blotting revealed a specific band of approximately 67 kDa in
      parathyroid tumors from PHP and SHP, with a much weaker such band detected in
      thyroid tumors. Menin expression was down-regulated in MEN1 samples, including
      nonsense mutation and deletion mutant. These findings suggest that menin is
      predominantly synthesized and stored in parathyroid tumors resulting from PHP and
      SHP.

PMID- 10902817
TI  - Thyroid hormone receptor gene expression in first trimester human fetal brain.
AB  - Maternal thyroid hormone is transferred to the fetus early in pregnancy and is
      postulated to regulate brain development. Thyroid hormone nuclear receptor (TR)
      proteins are present in fetal brain, but their isoformal composition is unknown.
      We therefore investigated the ontogeny of TR isoforms and related splice variants
      in first trimester human fetal brain (n = 9) by semi-quantitative reverse
      transcriptase-polymerase chain reaction analysis. Expression of the TRbeta1,
      TRalpha1 and c-erbAalpha2 isoforms was detected from 8.1 weeks gestation (wg). An
      additional truncated species was detected with the c-erbAalpha2 primer set,
      consistent with the c-erbAalpha3 splice variant previously described in the rat.
      All c-erbAalpha-derived transcripts were co-ordinately expressed and increased
      (ca. 8-fold) between 8.1 and 13.9 wg. A more complex ontogenic pattern was
      observed for TRbeta1, suggestive of a nadir between 8.4 and 12.0 wg. These
      findings point to an important role for the TRalpha1 isoform in mediating
      maternal thyroid hormone action during first trimester human fetal brain
      development.

PMID- 10902818
TI  - Ovarian hyporesponsiveness to follicle stimulating hormone in adolescent girls
      born small for gestational age.
AB  - Girls with reduced prenatal growth are known to have, at birth, a small ovarian
      fraction of primordial follicles and, in adolescence, a uterus and ovaries of
      small size. We have now examined whether reduced prenatal growth is also followed
      by changes in the relationships among FSH, inhibin B and estradiol in adolescent
      girls. We studied 48 post-menarcheal girls (age 13.6 +/- 1.4 yr) who were either
      born with an appropriate weight for gestational age (AGA; n=33; mean weight 3.3
      Kg) or born small for gestational age (SGA; n=15; mean weight 2.4 Kg). Serum FSH,
      inhibin B and estradiol concentrations were measured in the early follicular
      phase (range: day 5 +/- 3). SGA girls had, compared to AGA girls, elevated serum
      FSH (7.2 +/- 0.7 vs 4.5 +/- 0.3 IU/mL; p=0.0002), similar inhibin B (62.1 +/- 8.1
      vs 60.7 +/- 6.5 pg/mL) and lower estradiol concentrations (12.1 +/- 1.5 vs 21.2
      +/- 2.4 pg/mL; p=0.02). SGA girls thus displayed, early after menarche, a pattern
      that points to hyporesponsiveness of the ovarian granulosa cell fraction and that
      is reminiscent of reproductive aging. In conclusion, the gynecological correlates
      of prenatal growth restriction are herewith extended to include ovarian
      hyporesponsiveness to FSH in adolescence.

PMID- 10902819
TI  - Full remission of growth hormone (GH)-induced retinopathy after GH treatment
      discontinuation: long-term follow-up.

PMID- 10902820
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 10902821
TI  - Diamnionic monochorionic twin gestations: an overview.
AB  - Monochorionic (MC) twins account for about 20-30% of all twins, but contribute
      disproportionately to mortality, intrauterine growth restriction, and preterm
      delivery compared with dichorionic (DC) twins. This higher mortality in MC twins
      is likely due to the effects of placental morphologic characteristics, which
      include complex vascular communications between the twins associated with twin
      twin transfusion syndrome (TTTS), and the tendency for the common placenta to be
      shared either symmetrically or asymmetrically. In assessment of clinical outcomes
      for TTTS, artery to vein anastomoses in the absence of artery to artery or vein
      to vein, especially if present with placental asymmetry, carry the worse
      prognosis. Chorion status in twins forms the basis for clinical risk assessment
      and can be determined by 7 menstrual weeks using transvaginal sonography. The
      variable results reported in the literature for intertwin umbilical artery
      Doppler findings in MC twins may be explained by differences between sonographic
      and clinical criteria (including differential hemoglobin concentrations) reported
      by various investigators. Antenatal fetal Doppler assessment of the umbilical
      artery and cerebral arteries can help distinguish between TTTS and placental
      insufficiency in MC twins. Significant restriction of fetal growth occurs in
      about 25% of multiple gestations, accounting for about 17% of all growth-retarded
      infants. Redistribution of fetal blood (brain-sparing effect), as determined by
      Doppler interrogation of fetal cerebral and umbilical arteries, occurs more
      commonly in MC twins compared to DC twins and in growth-restricted MC twins
      compared to nongrowth-restricted MC twins. Overall, the prognosis is poorer for
      the donor twins in TTTS and there is a greater prenatal death rate for the donor
      (18-35%), and a higher overall survival rate for recipients following fetoscopic
      laser treatment. Finally, the clinical and sonographic findings suggest that the
      polyhydramnios/oligohydramnios sequence seen in MC twins likely represents a
      spectrum strongly linked to placental variables.

PMID- 10902822
TI  - Analysis of maternal circulation and renal function in physiologic pregnancies;
      parallel examinations of the changes in the cardiac output and the glomerular
      filtration rate.
AB  - OBJECTIVE: The aim of the study was to examine the temporal relations between the
      parameters of the maternal hemodynamics and homeostasis in different phases of
      pregnancy and the postpartum period. METHODS: Eleven healthy pregnant women were
      involved in the study. The value of the peripheric vasodilatation was measured by
      the ratio I/A of the maternal sphygmogram (I: incisure point, A: amplitude of the
      carotid pressure curve). The change of the cardiac output was determined by the
      ejection angle composed from maternal carotid sphygmogram and its first
      electrical derivate (dP/dT). The glomerular filtration rate (GFR) was measured
      with the in vitro radiofluorescent method. RESULTS: The primary peripheral
      vasodilatation and GFR increase occur early in the first trimester of a normal
      pregnancy, start to decrease at the end of the third trimester, and return to the
      normal value in the postpartum period. The increase of GFR precedes the increase
      of cardiac output. The cardiac output increases progressively from the first
      trimester and starts to decrease in the third trimester of a normal pregnancy.
      The extracellular volume increases at the beginning of first trimester
      progressively until the end of pregnancy and returns to the normal value in the
      postpartum period. DISCUSSION: The increase of GFR and the cardiac output during
      pregnancy are contributed to volume-establishment and to the cessation of the
      special "underfilled" condition of the maternal circulation in the normal
      pregnancy. We suppose that the maximal increase of GFR precedes the maximal
      increase of the cardiac output because the GFR increase is caused by maximal
      renal vasodilatation. The increase of cardiac output is caused in the first
      trimester by the shunt effect of the enhanced renal blood flow of maternal
      kidneys, and in the second and third trimester by the shunt effect of the feto
      placental unit and the shunt effect of the maternal kidneys.

PMID- 10902823
TI  - Predictive value of serial middle cerebral and renal artery pulsatility indices
      in fetuses with oligohydramnios.
AB  - OBJECTIVE: To determine if unexplained changes in the amniotic fluid index or
      pulsatility indices of the fetal renal, middle cerebral, or umbilical artery are
      predictive of perinatal outcome in pregnancies complicated by oligohydramnios.
      METHODS: Changes in amniotic fluid measurements and fetal vessel velocimetry in
      patients with oligohydramnios were evaluated for correlation with fetal outcome.
      Fourteen fetuses with oligohydramnios underwent serial sonography evaluating the
      amniotic fluid index and fetal middle cerebral, renal, and umbilical velocimetry.
      Matched controls and neonatal outcomes were obtained. RESULTS: Change in amniotic
      fluid index and in renal artery pulsatility index were inversely correlated.
      Change in the middle cerebral artery pulsatility index was different in infants
      with normal outcome compared to infants with adverse outcome CONCLUSIONS: Serial
      velocimetry of the middle cerebral artery may identify fetuses with
      oligohydramnios at risk for adverse outcomes.

PMID- 10902825
TI  - Factors associated with fetal macrosomia in offspring of gestational diabetic
      women.
AB  - OBJECTIVE: To determine whether there is a relationship between birthweight and
      interval between 1-h and 3-h glucose tolerance test (GTT) as well as other
      factors. METHODS: We performed a retrospective analysis of our computerized
      diabetes database for the years 1992-1997. Ninety-four women with gestational
      diabetes fulfilled the inclusion criteria (i.e., singleton gestation, term
      delivery, absence of medical conditions, and known interval between 1-h and 3-h
      GTT). They were evaluated based on prepregnancy body mass index (BMI), mean
      glucose values, interval between diagnostic testing, and gestational age of 3-h
      GTT. RESULTS: Subjects with GDM had a mean glucose value of 96.8 mg/dl and
      average prepregnancy BMI of 29.3 kg/m2. When GDM subjects with and without
      macrosomic infants were compared, mean glucose values (97.4 vs. 96.6 mg/dl) and
      mean interval (18.1 vs. 17.0 days) between diagnostic testing did not
      significantly differ. However, maternal prepregnancy BMI was higher in the group
      of women who gave birth to macrosomic infants (32.2 vs. 28.22 kg/m2, P = 0.008).
      Using stepwise multiple regression, maternal prepregnancy BMI was the only
      variable found to be predictive of macrosomia. CONCLUSION: We were unable to show
      a statistical relationship between interval of diagnostic testing and rate of
      macrosomia. However, we demonstrated a clear relationship between maternal BMI
      and infant birthweight.

PMID- 10902824
TI  - High incidence of respiratory distress syndrome (RDS) in infants born to mothers
      with placenta previa.
AB  - OBJECTIVE: To evaluate the incidence of respiratory distress syndrome (RDS) in
      infants born to mothers with placenta previa and to assess the risk factors for
      RDS. METHODS: Ninety-nine pregnant women with placenta previa who delivered by
      cesarean section at 30-35 weeks of gestation were compared retrospectively with
      102 pregnant women matched for week of gestation and birth year, who underwent
      elective cesarean section. Maternal characteristics, neonatal outcome, and
      incidence of RDS were analyzed. Umbilical cord blood samples were collected at
      delivery and were used to determine cortisol, epinephrine, and norepinephrine
      levels. Student's t-test, the chi-square test, and Fisher's exact test were used
      for statistical comparisons. P < 0.05 was considered significant. The Mann
      Whitney U test was used for comparison of continuous variables. RESULTS:
      Preeclampsia, histological chorioamnionitis, and premature rupture of membranes
      were significantly lower in the placenta previa group (placenta previa: 2.0% vs.
      control: 14.7%, P < 0.01; 14.1% vs. 30.1%, P < 0.01; 7.1% vs. 17.6%, P < 0.05,
      respectively). The incidence of RDS was significantly higher in the placenta
      previa group than in the control group (29.3% vs. 6.9%, P < 0.0001). The cortisol
      level in umbilical cord blood in the placenta previa group was lower than in the
      control group (median 7.3, range 4.4-14.9 microg/dl vs. median 10.6, range 4.9
      30.3 microg/dl, P < 0.05). There were no significant differences in epinephrine
      or norepinephrine levels between the two groups. CONCLUSIONS: The incidence of
      RDS in infants delivered at 30-35 weeks' gestation by cesarean section was
      significantly higher in mothers with placenta previa than in women without
      placenta previa. This may reflect decreased fetal stress since the cord blood
      cortisol levels were found to be lower in women with placenta previa.

PMID- 10902826
TI  - Second trimester maternal serum hCG level in an Asian population: normal
      reference values by ultrasound dating.
AB  - OBJECTIVE: To establish normative data of maternal serum chorionic gonadotropin
      (hCG) during the second trimester in an Asian population. METHODS: We measured
      the maternal serum hCG levels in 17,955 normal singleton pregnancies between 15
      and 21 weeks of gestation. The gestation age was estimated by measurement of
      fetal biparietal distance (BPD) in all cases. Median values of hCG at various
      gestational weeks were calculated and the values of hCG were converted to
      multiple of median (MoM). The incidences of low MoM value and high MoM value were
      also calculated. RESULTS: The mean and median values of hCG were 57,153 mIU/ml
      and 50,120 mIU/ml, respectively, at 15 weeks of gestation and then decreased to
      30,898 mIU/ml and 26,226 mIU/ml, respectively, at 21 weeks. We found 8.6% and
      9.4% of normal singleton pregnancies have hCG MoM values >2.0 MoM and <0.5 MoM,
      respectively. CONCLUSIONS: Our report provides a normal reference data of second
      trimester maternal hCG levels by ultrasound dating in an Asian population.

PMID- 10902827
TI  - Prospective evaluation of bone density in pregnant women receiving the low
      molecular weight heparin enoxaparin sodium.
AB  - OBJECTIVE: To evaluate changes in bone density in women receiving enoxaparin
      sodium during pregnancy. METHODS: Bone density in the proximal femur was serially
      measured in 16 women receiving enoxaparin sodium (40 mg daily) during pregnancy.
      Baseline measurements were taken within 2 weeks of starting therapy and then at 6
      8 weeks postpartum and 6 months postpartum. RESULTS: Patients received enoxaparin
      sodium for a mean duration of 25 weeks (range, 19-32 weeks). There was no
      significant change in mean bone density measurement from baseline measurements to
      the conclusion of therapy at 6 weeks postpartum and no patient experienced a
      decrease in bone mass of >10% at 6 weeks postpartum. By 6 months postpartum,
      there was a significant mean decrease in bone density (P = 0.02) and two of the
      14 patients evaluated (14%) experienced an overall bone loss of >10%. CONCLUSION:
      The prolonged used of enoxaparin sodium may not cause significant bone loss
      during pregnancy.

PMID- 10902828
TI  - Cost consequences of elimination of the routine group B streptococcus culture at
      a teaching hospital.
AB  - OBJECTIVE: To evaluate the cost consequence of the elimination of routine Group B
      streptococcus (GBS) cultures in pregnancy utilizing risk factor assessment
      management recommendations of the Center for Disease Control. METHODS: This
      retrospective study cohort population included all delivering patients from June
      1, 1996, to May 31, 1997, managed by the Morbidity Mortality Weekly Report (MMWR)
      guidelines May 31, 1996, for GBS in pregnancy compared to the previous 29 months
      cohort from January 1, 1994, to May 31, 1996, managed with routine GBS cultures
      done at 35-37 weeks. RESULTS: Of the 7,681 culture management control cohort
      patients, there were four neonates with culture-positive GBS sepsis (1/1,900).
      The cost for detection of a single positive culture in an affected neonate was
      $8,627 ($34,509/4) and there were 2,875 personnel hours expended. In contrast, of
      the 2,011 patients in the risk factor management cohort, there were two cases of
      neonatal GBS sepsis ($111,005). The cost for detection of a positive culture in
      an affected neonate was $1,579 ($3,159/2) and there were 263 personnel hours
      expended in the risk factor management group. In spite of these significant
      laboratory savings, we noted a concurrent increase in the total cost in the
      newborn nursery for septic work-ups and treatment from $2.4 million to $3.1
      million. CONCLUSION: Risk assessment management of GBS provided a savings of both
      money ($7,048/positive neonatal culture) and laboratory time (586 personnel
      hours/positive neonatal culture). However, these savings were more than offset by
      cost increases occurring in the newborn nursery ($400,000), demonstrating the
      necessity of practice patterns to undergo concurrent evaluation to verify cost
      savings and prevent shifting of expenses.

PMID- 10902829
TI  - Effects of single and multiple courses of antenatal glucocorticoids in preterm
      newborns less than 30 weeks' gestation.
AB  - BACKGROUND: We compared outcomes between neonates receiving either single course,
      multiple courses, or no antenatal glucocorticoid exposure. METHODS: We
      retrospectively identified neonates whose mothers received a single course (SIN)
      of dexamethasone, multiple (2-3) weekly courses (MULT), or no (NO)
      glucocorticoids. Multiple gestations and infants with chromosomal abnormalities
      or not receiving a full course of antenatal dexamethasone were excluded from the
      study. The incidences of the following outcomes were examined: respiratory
      distress syndrome (RDS), Grades III or IV intraventricular hemorrhage (IVH),
      bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of
      prematurity (ROP), sepsis, and in-hospital death. Means were compared with
      analysis of variance and outcome variable frequencies with chi-square test.
      RESULTS: A total of 147 infants were included in the analysis. There were no
      differences in the gestational age or growth parameters among the groups. As
      anticipated, infants exposed to antenatal glucocorticoids had a significantly
      lower incidence of morbidities (BPD, NEC, and IVH) than the unexposed infants.
      There were no differences in the incidence of RDS, IVH, BPD, NEC, ROP, PDA,
      sepsis, or death between the SIN and MULT groups. CONCLUSION: A single course of
      antenatal glucocorticoid therapy is associated with improved neonatal outcomes in
      infants less than 30 weeks' gestation. Multiple courses were not shown to confer
      additional benefits, but further investigation is required to definitively
      address the need for weekly treatment.

PMID- 10902830
TI  - Effect of antenatal exposure to paroxetine (paxil) on growth and physical
      maturation of mice offspring.
AB  - OBJECTIVE: Our purpose was to determine, in a placebo-controlled manner, whether
      antenatal exposure to paroxetine affected long-term growth and physical
      maturation of mice offspring. METHODS: Forty-one CD-1 mice consumed paroxetine (n
      = 21) or a placebo (n = 20) for 2 weeks before conception and throughout
      gestation. The daily dose of paroxetine (Paxil; 30 mg/kg/d) was known to achieve
      concentrations in the serum equivalent to the upper therapeutic level in humans
      and in the fetal brain equivalent to that of the adult mouse. Growth and physical
      maturation of the offspring were compared by paired t-test, Welch's corrected
      test, and Fisher's exact test. RESULTS: The maternal weight gain, litter sizes,
      number of fetal resorptions, and gestational age at delivery were not different
      between the paroxetine and the placebo-exposed offspring. Newborn pups exposed to
      paroxetine were more likely to have low birthweights (1.65 gm vs. 1.70 gm; P <
      0.05) and narrower heads (7.7 mm vs. 8.1 mm; P < 0.05). Body weight, body length,
      and head circumference measurements increased in a manner that was
      indistinguishable between the two groups of offspring, regardless of gender. No
      differences in achievement of physical milestones (lower incisor eruption, eye
      opening, and development of external genitalia) were noted between the two
      groups. The reproductive capability and the perinatal outcomes of the second
      generation offspring were unaffected by paroxetine exposure. CONCLUSION: A
      clinically relevant dose of paroxetine, when given throughout gestation, did not
      affect long-term growth and physical maturation of mice offspring.

PMID- 10902831
TI  - Role of frequency domain optical spectroscopy in the detection of neonatal brain
      hemorrhage--a newborn piglet study.
AB  - OBJECTIVE: Inability of continuous wave (CW) optical spectroscopy to measure
      changes in scattering, and the use of an arbitrary rather than an actual
      baseline, makes the CW method highly susceptible to errors that can lead to a
      false-positive or false-negative diagnosis. Our objective was to assess whether,
      and to what extent, the use of quantitative frequency domain spectroscopy would
      improve our ability to detect and monitor the development of brain hemorrhage.
      METHODS: A dual-channel frequency-domain tissue spectrometer (Model 96208, ISS,
      Inc., Champaign, IL) was used to monitor the development of experimental
      subcortical and periventricular-intraventricular hemorrhage (IVH) in 10 newborn
      piglets (blood injection model). The multidistance approach was employed to
      calculate the absorption and reduced scattering coefficients and hemoglobin
      changes from the ac, dc, and phase values acquired at four different source
      detector distances and at 752 nm and 830 nm. RESULTS: There were significant
      absorption and scattering changes in the subcortical hematoma (n = 5) and the IVH
      groups (n = 5). The smallest detectable amount of blood in the brain was 0.04 ml.
      Changes associated with subcortical hematoma were several times higher than those
      associated with IVH, and correlated better with the estimated cross-sectional
      area of the hematoma than with the volume of the injected blood. As opposed to
      IVH, there was a significant absorption difference between the injured
      (subcortical hematoma) and normal side of the brain, probably because in case of
      IVH a significant volume of the injected blood had accumulated/spread beyond the
      reach of the probe. CONCLUSION: Clearly, frequency-domain spectroscopy cannot
      increase our ability to quantify the volume (size) or the oxygenation of the
      injected blood, especially in the case of IVH. However, the ability to quantify
      the baseline tissue absorption and scattering would significantly improve
      diagnostic performance, and may allow for early identification and treatment of
      neonatal brain hemorrhage.

PMID- 10902832
TI  - Uterine prolapse associated with bladder exstrophy: surgical management and
      subsequent pregnancy.
AB  - Congenital bladder exstrophy affects 1 in 125,000 to 250,000 females. Consisting
      of absence of the anterior abdominal wall with exposure of the ureteral orifices,
      failure of pubic symphysis fusion, and deficient anterior pelvic diaphragm
      musculature, bladder exstrophy is frequently associated with genital prolapse.
      Pregnancy may be complicated by recurrent urinary tract infections, preterm
      labor, mild procidentia, and malpresentation. Due to the rarity of the condition,
      there is a corresponding scarcity of obstetric literature regarding management
      during pregnancy. We report the case of a young woman with surgically repaired
      bladder exstrophy who developed genital prolapse. The uterus was suspended using
      a sacral colpopexy utilizing a Gore-Tex graft. Subsequently, the patient became
      pregnant and delivered a healthy male infant at 35 weeks' gestation via cesarean
      section (without recurrence of the genital prolapse postpartum). Sacral colpopexy
      to correct genital prolapse associated with bladder exstrophy may preserve
      fertility in young patients.

PMID- 10902833
TI  - Nuchal cord position in breech presentation: case report.
AB  - Nuchal cord position in breech presentation has been previously reported and
      classified into two types. We report a case of breech presentation with nuchal
      cord. Prenatal ultrasound showed a single nuchal cord inserted into the placenta
      located on the mid-posterior uterine wall at the level of the fetal neck.
      Elective cesarean section was performed at 37 weeks. We discuss the clinical
      significance of nuchat cord.

PMID- 10902834
TI  - Prevention and control of meningococcal disease. Recommendations of the Advisory
      Committee on Immunization Practices (ACIP).
AB  - This report summarizes and updates an earlier published statement issued by the
      Advisory Committee on Immunization Practices concerning the control and
      prevention of meningococcal disease (MMWR 1997:46[No. RR-5]:1-21) and provides
      updated recommendations regarding the use of meningococcal vaccine.

PMID- 10902835
TI  - Meningococcal disease and college students. Recommendations of the Advisory
      Committee on Immunization Practices (ACIP).
AB  - This report provides information regarding the modestly increased risk for
      meningococcal disease among college freshmen, particularly those who live in
      dormitories or residence halls. It presents recommendations developed by the
      Advisory Committee on Immunization Practices regarding the education of students
      and parents about meningococcal disease and the polysaccharide meningococcal
      vaccine so that they can make informed decisions regarding vaccination.

PMID- 10902836
TI  - Trace metals in liver, skin and muscle of Lethrinus lentjan fish species in
      relation to body length and sex.
AB  - A post-Gulf sea water pollution assessment program was carried out in the liver,
      skin and muscle tissues of the localized Lethrinus lentjan fish species [Family:
      Lethrinidae (Teleost)]. Monitoring the concentration of the major heavy metals at
      different sites along the western coast of the United Arab Emirates (UAE) on the
      Arabian Gulf was studied. The concentrations of Zn, Cu and Mn were found to
      follow the order: liver > skin > muscle while the cadmium level follows the
      sequence: liver > muscle > skin. The influence of fish sex and body length on the
      metal accumulation of those metals in the tested fish organs was critically
      investigated. The average metal concentrations in liver, skin and muscle of
      female fish were found to be higher than those found in the male fish. The
      detected metal levels were generally similar to previous pre-war, 1991 levels.
      The study concludes that the marine fish from the Arabian Gulf are comparatively
      clean and do not constitute a risk for human health.

PMID- 10902837
TI  - Lead contamination of the environment in Russia.
AB  - Contamination of the environment by lead is recognised throughout the world as
      one of the major environmental problems. The main goal of this paper is to
      present objective and systematic data on this problem in Russia. Here we show
      that in spite of a crisis of industry, the degree of contamination of various
      parts of the environment in urban areas remains very high. A considerable
      proportion of the urban population of the country, especially children, are
      running the risk of a detrimental effect of lead compounds in various parts of
      the environment and in foodstuffs.

PMID- 10902838
TI  - Metal phase associations in soils from an urban watershed, Honolulu, Hawaii.
AB  - Soils of Manoa watershed, Hawaii, have received varying inputs of anthropogenic
      trace metals, with roadside soils primarily influenced by automobile
      contributions. A four-stage sequential extraction procedure was used to
      fractionate 13 topsoil (0-2.5 cm) and 13 subsoil (7.5-10.0 cm) samples into: (i)
      an adsorbed, exchangeable and carbonate (AEC) phase; (ii) a reducible phase;
      (iii) an oxidizable phase; and (iv) a residual phase. Phases (i)-(iii) were
      considered 'labile', with the residual fraction 'non-labile' under normal
      circumstances. An examination of eight elements (Al, Co, Cu, Fe, Mn, Ni, Pb and
      Zn) indicated that Pb was the trace metal most impacted by anthropogenic inputs.
      Roadside soil Pb enrichment was apparent with data from a 0.5 M HCI leach
      exhibiting a maximum concentration of 1000 mg/kg compared with a median
      background value of 12 mg/kg. Sequential extraction results indicated the
      following order with respect to phase dominance for Pb: reducible > residual >
      oxidizable > AEC. The identification of the reducible phase as the primary pool
      of available Pb supports previous work from temperate roadside soil environments.
      The reducible phase is characterized by hydrous Fe and Mn oxides and mobilization
      of fixed elements can occur with decreases in pH and redox potential. Iron was
      the least labile of the elements examined with only 5-6% of total Fe removed by
      the first three steps of the extraction procedure. Lead had the highest labile
      percentage with average values between 74 and 81%. Therefore, results from this
      study support earlier research in this watershed which identified Pb as the
      primary trace metal of concern from a contamination perspective.

PMID- 10902839
TI  - Home sweet home? A case study of household dust contamination in Hong Kong.
AB  - It is well recognized that many heavy metals have chronic effects on humans and
      as such, they are potential environmental health hazards, particularly to young
      children (see, for example, Body P, Inglis G, Dolan P, Mulcahy D. Environmental
      lead: a review. Crit Rev Environ Control 1991;20:299-310). Considerable attention
      has been paid to the study of metal pollution in city air, roadside dusts and
      soils. However, there is a lack of concern of the presence of trace metals in
      house dust in the populous city of Hong Kong, where it has traditionally been
      assumed that such pollutants are rapidly dispersed by ocean breezes. This
      research aims at quantifying the concentrations of heavy metals within the home
      environment in Hong Kong and their relationships with environmental factors. The
      results of this study seem to suggest that traffic and the age of the building
      and neighborhood are more important factors than the types of industry and
      socioeconomic status in affecting household dust contamination. The metal burdens
      in Kwung Tong, an old area with heavy traffic, are significantly higher than
      other districts. When a Kruskal-Wallis one-way analysis of variance was performed
      on the ranked metal concentrations in different housing districts, the Chi-square
      values are all significant at a probability level of < 0.001. This might be
      attributable to the fact that there is no highly contaminating industries (such
      as metal smelters, battery plants and petrochemicals) in Hong Kong. The dust
      metals may travel from the roads, through the windows and balconies, into the
      houses, as those homes that do not have their windows opened often had a lower
      level of contaminants in their house dust (median Cd= 3.6 microg/g; median Cu =
      313.2 microg/g; median Pb = 144.6 microg/g; median Mn = 211.6 microg/g; and
      median Zn = 1,333.7 microg/g). Moreover, those occupants who sweep their floors
      or dust their furniture on daily bases, or use vacuum cleaners, had a lower level
      of metals inside their houses. Another finding of interest is that the color of
      the wall paint used in the house may be another factor influencing the
      contamination levels.

PMID- 10902840
TI  - Pentachlorophenol in indoor environments. Correlation of PCP concentrations in
      air and settled dust from floors.
AB  - The investigation of settled dust is a proven and simple screening-method for
      considering indoor contamination for semivolatile compounds. Here we investigate
      the correlation of PCP concentrations in air and freshly settled dust from
      floors. Air and dust samples were taken from 75 rooms in 30 buildings with
      suspicion of an application of PCP-containing wood preservatives. Sampling was
      repeated four times within 18 months. PCP air concentrations were found in the
      range of <0.3-576 ng m-3 (mean value 25.3 ng m-3, median 2.5 ng m-3). PCP dust
      concentrations were found in the range of 0.083-79 microg g-1 (mean value 3.5
      microg g-1, median 1.1 microg g-1. A weak highly significant correlation (P <
      0.0001) with a correlation coefficient of R2 = 0.433, of the PCP concentration in
      dust with the PCP concentration in air, was observed. Measurement of PCP
      concentrations in dust, therefore, is a suitable screening method for the
      evaluation of indoor contamination with PCP. Due to the high dispersion of the
      data it is not possible to calculate PCP concentrations in air from
      concentrations in dust although a highly significant correlation of the PCP
      concentrations in air and dust was found.

PMID- 10902841
TI  - Single particle and inorganic characterization of rainwater collected above the
      North Sea
AB  - Suspended matter and the dissolved fraction of rainwater collected above the
      North Sea were characterized using electron probe X-ray microanalysis (EPXMA),
      inductively coupled plasma-optical emission spectrometry (ICP-OES) and ion
      chromatography (IC), respectively. Suspended particulate matter was dominated by
      aluminosilicates and organic particles. Fifteen particle types describe the
      composition of the North Sea rainwater suspended matter. Factor analysis,
      particle size distributions and manual EPXMA measurements illustrated the complex
      genesis of different particle types: terrigenous; biogenic (both marine and
      continental); and anthropogenic. It was demonstrated that at the beginning of a
      shower of rain the coarse particles that are present in the air under the cloud
      are washed out, while during the second phase rainout particles, formed in the
      cloud, become more important due to the absence of new coarse particles under the
      cloud. Above the sea, the total amount of suspended matter (TSM) is much smaller
      and more variable than above the land and also the decrease in particle diameter
      is less visible. Approximately 10% of the studied particles contained trace heavy
      metals. The dissolved compounds in the North Sea rainwater were also variable in
      time and space. In general, over a short period of time, the concentrations of
      all dissolved compounds seem to decrease during a shower, but this decrease is
      much larger above land than above sea. The concentrations of dissolved trace
      metals present in rainwater above the southern North Sea has decreased over the
      last 15 years.

PMID- 10902842
TI  - Use of native and transplanted mosses as complementary techniques for
      biomonitoring mercury around an industrial facility.
AB  - Terrestrial mosses were used simultaneously in passive (native species,
      Scleropodium purum and Hypnum cupressiforme) and active (S. purum transplants in
      moss bags) biomonitoring techniques in a study that aimed to demonstrate the
      compatibility of the two methods by detailed investigation of the spatial
      distribution of mercury in the surroundings of a chlor-alkali plant. Native
      mosses were sampled and transplants exposed (for periods of 30 days) at two
      different times of the year in order to take into account different environmental
      conditions (precipitation, temperature, prevailing winds, etc.). The
      concentrations of Hg in the native mosses ranged between 0.04 and 11.78 microg g(
      1) in February and 0.26 and 12.7 microg g(-1) in September; in the transplants
      the concentrations ranged between 0.39 and 1.9 microg g(-1) in June and 0.036 and
      2.75 microg g(-1) in November. These values are all within the ranges reported in
      the literature. The total concentrations were transformed into either
      contamination factors (CF) (by taking into account the background levels of Hg in
      the native mosses) or enrichment factors (EF) (by taking into account the initial
      concentrations in the transplants). In both cases, there was a clear relationship
      with the distance from the source of emission, irrespective of the time of year.
      Within the range of distances for which data were available for natives and
      transplants, the CF and EF were highly correlated. This implies that transplants
      sited in the area immediately surrounding the plant, where the density of native
      mosses was very low, can be used to determine the degree of contamination in this
      area. The study also illustrated that the native moss appeared to adapt to the
      surrounding environment because at an equal distance (> 500 m) from the source of
      emission the value of the CF for native mosses fell to 1, but the EF for
      transplanted mosses remained still high (5.2).

PMID- 10902844
TI  - Uptake of cations under two different water regimes in a boreal scots pine
      forest.
AB  - There is still much to find out about how trees react to changing nutrient
      conditions. In this cation uptake study, 134Cs and 22Na were injected between the
      humus and the mineral soil, and into a 20-cm depth in the mineral soil,
      respectively. Half of the experimental site was subjected to desiccation in 1995
      and 1996, while the other half was subjected to irrigation in 1995, and
      desiccation in 1996. One month after the injections, the concentration of 134Cs
      in the xylem sap was higher in the irrigated plots (ID) than in the desiccated
      plots (DD). In August 1995, the difference in the 134Cs concentration in the
      xylem sap was even higher between the treatments. In 1995, 22Na was also higher
      in the xylem sap on the ID plots than on the DD plots, but not significantly.
      Exponential relationships were found between the amount of 134Cs and 22Na in the
      xylem sap; the relative water uptake from humus and 0-10-cm mineral soil (134Cs);
      and 10-25-cm mineral soil (22Na) in July 1995, when the tracers had not yet
      reached the top of the boles. The relative uptake of injected 22Na was larger
      than that of injected 134Cs, probably due to low exchangeability of Cs in the
      soil. One year after the injection (1996), more 134Cs was found in the wood,
      bark, needles and cones on the plots irrigated in 1995 than on the desiccated
      plots. The content of 134Cs in the stem wood and stump amounted to nearly 80% of
      the total uptake in the trees. The Cs distribution 1 year after the Chernobyl
      accident was dominated by Cs on/in needles and bark. After 10 years of
      redistribution, the Chernobyl Cs content of the different parts of the trees
      approached that of K.

PMID- 10902843
TI  - Estimating steroid oestrogen inputs into activated sludge treatment works and
      observations on their removal from the effluent.
AB  - A method to predict steroid oestrogen inputs into sewage works is described and
      tested against available data. For oestradiol (E2), 68% of the predictions were
      within 50% of the actual measured value, and for oestrone (E1), 52% of the
      estimations were within 50% of the measured value. Predictions for
      ethinyloestradiol (EE2), which are particularly sensitive to assumptions on the
      number of people taking the oral contraceptive, were less accurate. Five Italian
      and three Dutch activated sludge treatment works (STW) were sampled on two to
      three occasions for E2, E1, EE2 and E3 (E3 only in Italy) in both influent and
      effluent waters. High concentrations of E3 were found in the influent, as
      predicted, with a mean of 57 ng/1 and a mean of 10 ng/l in the effluent. Using
      the currently available data collected from composite samples, an average of 88%
      of E2 and 74% of E1 would appear to be removed by the activated sludge process.

PMID- 10902845
TI  - Comparative erythropoietic effects of three vanadium compounds.
AB  - The biotoxic effects of vanadium are variable depending upon a number of factors
      including the oxidation state of the test compound. This study reports the
      effects of three vanadium compounds on peripheral erythrocytes. On day 0 female
      ICR mice received a single injection of vanadium chloride (V-III), vanadyl
      sulfate (V-IV), or sodium orthovandate (V-V). At scheduled intervals post
      injection, the number of circulating erythrocytes [red blood cells per millimeter
      cubed (RBC/mm3)], reticulocyte percentages, and radioiron uptake percentages were
      determined and compared to mice receiving saline only. Data show that all three
      test substances promoted a significant lowering of RBC/mm3 beginning on day 1 for
      V-IV and V-V and on day 2 for V-III through day 4. The reticulocyte percentages
      increase followed the same time course as that of the peripheral RBC decrease.
      Peak reticulocytosis was noted on days 2 and 4 for all three vanadium-treated
      groups; for V-IV and V-V the increase continued to day 6. Radioiron data showed
      an erythropoietic stimulation by a significant increase in uptake percentages on
      days 4-6 after vanadium injections compared to saline-treated controls.

PMID- 10902846
TI  - Characterisation of riverine particulate organic matter by pyrolysis-gas
      chromatography-mass spectrometry.
AB  - Particulate matter samples were collected in the mountainous section and river
      mouth at the Tech River basin, south France, during flood (December 1996) and
      summer (September 1997) periods. Suspended material was analysed by pyrolysis-gas
      chromatography-mass spectrometry (Py-GC-MS) and 23 identified pyrolysis products
      were divided into five main fractions: aminosugars, aromatic hydrocarbons,
      polysaccharides, phenols and nitrogenous compounds. Analysis of relative amounts
      of these fractions revealed neither significant spatial nor temporal changes in
      the particulate organic matter composition. Nevertheless, their specific
      composition showed that during flooding there is a certain homogeneity in the
      composition of the riverine particulate organic matter, with more degraded
      material of pedogenic (allochthonous) character, and during the summer the
      results suggest the presence of two components, allochthonous and autochthonous.

PMID- 10902847
TI  - Protecting environmental quality and human health: strategies for harmonisation.
AB  - In September 1999 the MRC Institute for Environment and Health hosted a
      multidisciplinary seminar on the harmonisation of strategies to protect
      environmental quality and human health. The objectives of the meeting were to
      share information about ways in which the protection of the environment and human
      health can be harmonised, and, by bringing together an audience representing a
      range of disciplines, interests and sectors, to explore how these may be
      integrated to inform policy, decision-making and the management of risks. Key
      conclusions from the seminar focused on the importance of sustainable
      development, harmonising risk assessment and the role of stakeholder involvement.
      The necessary move from an expert-based to a dialogue-based process will require
      concerted efforts on the part of scientists, policy-makers, regulators, industry
      and the public.

PMID- 10902848
TI  - Content of minor and trace elements, and organic nutrients in representative
      mixed total diet composites from the USA.
AB  - As part of an international nutrition project sponsored by the International
      Atomic Energy Agency (see footnote), Vienna, Austria, a number of bench-mark
      mixed total diet composites from the United States were collected and analyzed
      for minor and trace elements. In this segment of the project, the daily dietary
      intakes of the minor elements Ca, Cl, K, Mg, N and P and the trace elements Al,
      As, Au, Br, Cd, Co, Cr, Cs, Cu, Fe, Hg, I, Mn, Mo, Ni, Pb, Rb, Sb, Sc, Se, Sn,
      Sr, V, Zn and W were determined in mixed total diet composites of foods collected
      in the FDA Total Diet Study (FDA-TDS). These diets are representative of foods
      consumed by 25-30-year-old males (representing the mixed population groups in the
      United States), the highest of eight intake groups in the TDS scheme. In order to
      link the US mixed diet composite results from this study group to the more
      comprehensive information generated by the FDA-TDS, the results are compared with
      the same age-sex group published by the FDA-TDS scheme. The FDA-TDS scheme is
      based on individual analysis of the 201 food items, with resultant calculation of
      the daily intake representative of various age-sex groups. The comparison shows
      excellent agreement for 21 elements which have been investigated by both
      approaches. Additional elements are reported in the US mixed diet composites from
      the present study which demonstrate a valuable supplement to the data obtained by
      FDA-TDS scheme. Further the mixed total diet composite approach has also proven
      useful for the assessment of dietary intake of proximates (protein, fat,
      carbohydrates), fiber and phytate. In addition, vitamins thiamin, riboflavin,
      niacin, B6, B12, pantothenic acid, folic acid and biotin were also assayed in
      these composites.

PMID- 10902849
TI  - Perchlorate uptake by salt cedar (Tamarix ramosissima) in the Las Vegas wash
      riparian ecosystem.
AB  - Perchlorate ion (ClO4-) has been identified in samples of dormant salt cedar
      (Tamarix ramosissima) growing in the Las Vegas Wash. Perchlorate is an oxidant,
      but its reduction is kinetically hindered. Concern over thyroid effects caused
      the Environmental Protection Agency (EPA) to add perchlorate to the drinking
      water Contaminant Candidate List (CCL). Beginning in 2001, utilities will look
      for perchlorate under the Unregulated Contaminants Monitoring Rule (UCMR). In
      wood samples acquired from the same plant growing in a contaminated stream,
      perchlorate concentrations were found as follows: 5-6 microg g(-1) in dry twigs
      extending above the water and 300 microg g(-1) in stalks immersed in the stream.
      Perchlorate was leached from samples of wood, and the resulting solutions were
      analyzed by ion chromatography after clean-up. The identification was confirmed
      by electrospray ionization mass spectrometry after complexation of perchlorate
      with decyltrimethylammonium cation. Because salt cedar is regarded as an invasive
      species, there are large scale programs aimed at eliminating it. However, this
      work suggests that salt cedar might play a role in the ecological distribution of
      perchlorate as an environmental contaminant. Consequently, a thorough
      investigation of the fate and transport of perchlorate in tamarisks is required
      to assess the effects that eradication might have on perchlorate-tainted riparian
      ecosystems, such as the Las Vegas Wash. This is especially important since water
      from the wash enters Lake Mead and the Colorado River and has the potential to
      affect the potable water source of tens of millions of people as well as
      irrigation water used on a variety of crops, including much of the lettuce
      produced in the USA.

PMID- 10902850
TI  - Natural tritium levels in tender and ripe coconut fruit (Cocos nucifera L.): a
      preliminary examination.
AB  - Tissue Free Water Tritium concentrations (TFWT) were determined in tender coconut
      (Cocos nucifera L.) water, ripe coconut water, and kernel milk water, and
      compared with the same in groundwater collected from the vicinity of the trees.
      Samples with a very low tritium content were enriched by the alkaline
      electrolysis method. All of the samples were analyzed for tritium content in an
      ultra-low level liquid scintillation spectrometer. The TFWT in kernel milk water
      was found to be approximately 20-40 times higher than that in the groundwater.
      The tritium concentration in descending order in these samples is: kernel milk
      water, ripe coconut water, tender coconut water, and groundwater. The
      concentration of tritium increases as the fruit grows and the significantly high
      concentration in the kernel milk water suggests enrichment during the growth of
      the fruit.

PMID- 10902852
TI  - Prognostic significance of p53 and p21WAF1/CIP1 immunoreactivity and tumor
      micronecrosis for recurrence of meningiomas.
AB  - Recurrence is an important factor for prognosis of meningioma patients, this also
      occurring with some lesions diagnosed histopathologically as benign. To analyze
      their relationships with clinicopathological factors, p53 and p21WAF1/CIP1
      immunoreactivity, 80 meningiomas were classified into four groups with regard to
      the World Health Organization (WHO) histological classification and recurrence:
      40 cases of Group I (typical type)-NR (no recurrence); five cases of Group I-R
      (recurrence); 20 cases of Group II (atypical or anaplastic type)-NR and 15 cases
      of Group II-R. Micronecrosis was detected in 25% of Group II-NR and 73.3% of
      Group II-R (P = 0.007, odds ratio (OR) = 8.25, 95% confidence interval (CI) =
      1.79-38.01). Patients receiving radiation therapy had a lower risk of recurrence
      (P = 0.041, OR = 0.20, 95% CI = 0.05-0.85). Immunoreactivity for p53 protein was
      positive in 22% of Group I and 54% or Group II (P = 0.005), and in 80% of Group I
      R and 15% of Group I-NR (P = 0.006, OR = 22.7, 95% CI = 2.15-239.4). p21WAF1/CIP1
      protein was detected in 22% of Group I and 48% of Group II (P = 0.017), but with
      no link to recurrence. Multivariate analysis also showed p53 immunoreactivity in
      Group I (benign lesions) and micronecrosis in Group II (atypical/anaplastic
      meningiomas) to be strong prognostic factors for recurrence (P < 0.05). These
      results indicate that p53 immunoreactivity and micronecrosis can help predicting
      recurrence of meningiomas.

PMID- 10902851
TI  - Long-term immunological memory in the resistance of rats to transplanted
      intracerebral 9L gliosarcoma (9LGS) following subcutaneous immunization with 9LGS
      cells.
AB  - Glioblastoma multiforme (GBM) is the most common primary human brain tumor. About
      7000 new cases are diagnosed yearly in the USA. Despite current neurosurgical and
      postoperative radiotherapeutic tumor cytoreduction methods, in most cases occult
      foci of tumor cells infiltrate surrounding edematous brain tissues and cause
      recurrent disease within one year. GBM is almost invariably fatal within a few
      years after it is diagnosed. Our goal is to achieve long-term control of GBM by
      combining immunoprophylaxis with a radiation-based technique, such as boron
      neutron-capture therapy (BNCT), potentially capable of specifically targeting the
      infiltrating tumor cells while sparing the surrounding normal brain tissue. It
      has long been known that the subcutaneous (sc) injection of irradiated cells or
      untreated cultured cells (and the removal of the resulting tumors) derived from
      the well characterized, highly immunogenic 9L gliosarcoma (9LGS) rat model into
      young isogenic rats can prevent tumor growth after subsequent sc or intracranial
      (ic) injection of untreated, otherwise lethal 9LGS cells. In this study we have
      confirmed, quantified and extended those findings to study the efficacy of such
      immunological memory in normal aging rats and in aging rats previously treated
      for ic 9LGS tumors by BNCT. (1) The sc injection of 5,000,000 untreated 9LGS
      cells and the surgical removal of the resulting tumors (method A) protected 80%
      of normal young rats from an ic challenge with 10,000 untreated 9LGS cells, and a
      single sc injection of 5,000,000 lethally X-irradiated 9LGS cells (method B)
      protected 66% of them, but multiple sc injections with a crude particulate
      fraction prepared from 9LGS cells were not protective. Protection is long-lasting
      since contralateral ic rechallenge of six-month survivors with an injection of
      10,000 viable 9LGS cells resulted in 100% survival. (2) Normal one-year-old rats
      were only slightly less protected than were normal young rats, approximately 70%
      rather than approximately 80% (method A) and approximately 60% rather than
      approximately 66% (method B). (3) BNCT treatment alone resulted in partial
      immunological protection, as 30% of one-year post-BNCT survivors of ic 9LGS
      tumors prevailed after contralateral ic rechallenge with 10,000 viable 9LGS
      cells. Moreover a single sc immunization with 5,000,000 untreated 9LGS cells
      prior to ic rechallenge boosted survival from 30% to 100%. The relevance of these
      observations to strategies of preclinical experimentation for immunoprophylaxis
      of malignant gliomas is discussed.

PMID- 10902853
TI  - Acetaminophen selectively reduces glioma cell growth and increases
      radiosensitivity in culture.
AB  - Glioblastoma multiforme (GBM) is a highly lethal brain cancer. Using cultures of
      rodent and human malignant glioma cell lines, we demonstrated that millimolar
      concentrations of acetylsalicylate, acetaminophen, and ibuprofen all
      significantly reduce cell numbers after several days of culture. However, their
      mechanisms of action may vary, as demonstrated by (1) differences in the
      morphological changes produced by these compounds; (2) varied responses to these
      drugs with respect to toxicity kinetics; and (3) respective rates of cell
      proliferation, DNA synthesis, and mitotic index. We studied the effects of
      acetaminophen on relative cell number further. Evidence is presented that
      acetaminophen induced cell death by an apoptotic mechanism after a brief burst of
      mitosis in which cell numbers increased transiently, followed by a reduction in
      cell number and an increase in DNA fragmentation, as evidenced by terminal
      deoxytransferase-mediated dUTP-biotin nick end labeling (TUNEL) analysis. Using
      cultures of adult human brain and embryonic rat brain, we demonstrated that
      glioma cells were several-fold more sensitive to acetaminophen than normal brain
      cells in culture. Finally, subtoxic doses of acetaminophen increased the
      sensitivity of the human glioma cells in culture to ionizing radiation. Taken
      together, these results suggest that acetaminophen may prove to be a useful
      therapeutic agent in the treatment of human brain tumors.

PMID- 10902855
TI  - Craniofacial hemangiopericytoma associated with oncogenic osteomalacia: case
      report.
AB  - A craniofacial hemangiopericytoma associated with oncogenic osteomalacia is
      described and the literature is reviewed. A 46 year-old male with multiple
      fractures and hypophosphatemia was found to have a craniofacial mass extending
      from the right ethmoid sinus into the right frontal lobe. Initial detection of
      the tumor was made with an 111Indium-pentreotide scan (Octreoscan). Gross total
      resection of the tumor was achieved and the patient received postoperative
      radiation therapy. One year after surgery, the patient remains free of tumor with
      significant increase in bone density and normal phosphate levels. This is the
      first report of a hemangiopericytoma invading the brain that was associated with
      paraneoplastic hypophosphatemia and osteomalacia. Also, this is the first
      reported detection of a hemangiopericytoma by an Octreoscan. Primary detection
      and secondary surveillance of hemangiopericytomas may be possible with serial
      Octreoscans.

PMID- 10902854
TI  - The combination of boron neutron-capture therapy and immunoprophylaxis for
      advanced intracerebral gliosarcomas in rats.
AB  - Glioblastoma multiforme (GBM) is the most common primary human brain tumor. About
      7000 new cases are diagnosed yearly in the USA and GBM is almost invariably fatal
      within a few years after it is diagnosed. Despite current neurosurgical and
      radiotherapeutic tumor cytoreduction methods, in most cases occult foci of tumor
      cells infiltrate surrounding brain tissues and cause recurrent disease. Therefore
      the combination of neurosurgical and radiotherapeutic debulking methods with
      therapies to inhibit occult GBM cells should improve prognosis. In this study we
      have combined boron neutron-capture therapy (BNCT), a novel binary
      radiotherapeutic treatment modality that selectively irradiates tumor tissue and
      largely spares normal brain tissue, with immunoprophylaxis, a form of active
      immunization initiated soon after BNCT treatment, to treat advanced, clinically
      relevantly-sized brain tumors in rats. Using a malignant rat glioma model of high
      immunogenicity, the 9L gliosarcoma, we have shown that about half of the rats
      that would have died after receiving BNCT debulking alone, survived after
      receiving BNCT plus immunoprophylaxis. Further, most of the surviving rats
      display immunological-based resistance to recurrent 9LGS growth six months or
      more after treatment. To our knowledge this study represents the first time BNCT
      and immunoprophylaxis have been combined to treat advanced brain tumors in rats.

PMID- 10902857
TI  - Does measurement of inhibin have a clinical role?

PMID- 10902858
TI  - Measurement of osteocalcin.

PMID- 10902859
TI  - Cardiac troponin I: a marker for post-burn cardiac injury.
AB  - Cardiac troponin I (cTnI) was measured by chemiluminescent immunoassay following
      burn injury. Thirty patients [total body surface area (TBSA) of burn 15-98%] were
      included in this study and each had four to six blood samples collected at 2-day
      intervals between the 5th and 14th days post-burn. All patients were found to
      have increased cTnI on two or more occasions. The mean cTnI concentration was
      significantly higher in patients with TBSA of burn > 30% (0.34 microg/L compared
      with 0.09 microg/L, P<0.001) and in those with obvious burn wound exudation (0.32
      microg/L compared with 0.12 microg/L, P<0.01). cTnI concentrations peaked at the
      time when there was obvious burn wound exudation or spontaneous separation of
      eschar, then decreased after surgical excision. Two patients with persistently
      high cTnI concentrations developed tachycardia. We conclude that burned patients
      have varying degrees of non-ischaemic cardiac injury, manifesting as leakage of
      cTnI from myocytes into the circulation.

PMID- 10902856
TI  - Evaluation of early response to SU101 target-based therapy in patients with
      recurrent supratentorial malignant gliomas using FDG PET and Gd-DTPA MRI.
AB  - Changes in [18F]-2-fluoro-2-deoxyglucose (FDG) uptake and gadopentetate
      dimeglumine (Gd-DTPA) enhancement before and after the first course of treatment
      with a cytostatic agent SU101 (N-[(4-trifluoromethyl)-phenyl]-5-methylisoxazole-4
      carboxamide, SUGEN) were assessed using positron emission tomography (PET) and
      magnetic resonance imaging (MRI) in a pilot study of 8 patients with recurrent
      supratentorial malignant gliomas. The localization and the volume of Gd-DTPA
      enhancement and FDG hypermetabolism were analyzed. PET and MRI studies were
      performed one week before and 7.6+/-3.7 weeks after administration of SU101. The
      ratios of mean tumor activity to mean contralateral white matter and ipsilateral
      cerebellar activity were calculated for tumor regions, and SUV values corrected
      to the subjects' body surface area and glucose level (SUVbsa*glu) were calculated
      for nontumor regions. Five patients had a substantial increase of tumor volume on
      both PET and MRI during the first course of SU101. PET and MRI showed roughly
      equivalent volume changes. Large tumor volume increases were associated with a
      short time to clinical progression. The metabolic change in the tumor following
      the first course of SU101 varied from patient to patient, ranging from a 31%
      reduction to a 43% increase in FDG uptake ratio. Changes in FDG uptake were not
      predictive of time to progression or survival. In 2 patients with marked clinical
      deterioration and rapid tumor growth, there were differences in localization of
      Gd-DTPA enhancement and FDG hypermetabolism suggesting that hypermetabolism
      beyond the area of contrast enhancement may be of value in predicting rapid
      progression of high-grade glioma. SU101 did not induce any appreciable changes in
      SUVbsa*glu for non-tumor brain in 6 of 8 patients.

PMID- 10902860
TI  - Effects of bilirubin and its photoisomers on direct bilirubin measurement using
      bilirubin oxidase.
AB  - We examined the reactivity of human serum albumin-bound bilirubin and its
      photoisomers as substrates for a direct bilirubin assay using bilirubin oxidase.
      The reduction of (EZ)-cyclobilirubin reached 100% 5 min after addition of the
      enzyme at any pH tested (3.5-7.4) in 0.1 mol/L phosphate buffer, whereas the
      reduction of (ZE)-bilirubin or (ZZ)-bilirubin reached 100% only below pH 4.5 or
      5.5, respectively. (ZZ)-Bilirubin and its photoisomers did not react in citrate
      lactate buffer at pH 3.7. The circular dichroism spectrum of (ZZ)-bilirubin in
      this buffer did not show a positive Cotton effect. These results indicate that a
      three-dimensional structure surrounding the reaction site of bilirubin is
      important for the reactivity with bilirubin oxidase.

PMID- 10902861
TI  - Assessment of iron absorption from ferric trimaltol.
AB  - Therapeutic iron compounds have limited absorption and often have side-effects,
      which limits patient compliance. Iron trimaltol is a novel, stable complex,
      formed between ferric iron (Fe3+) and maltol (3-hydroxy-2-methyl-4-pyrone), and
      is effective in the treatment of iron deficiency anaemia with few side-effects.
      However, the kinetics of iron absorption from ferric trimaltol and the
      reliability of normal colorimetric analysis in detecting iron absorbed from this
      complex have not been established. We measured increases in serum iron levels in
      12 volunteers following oral challenge with four different pharmaceutical
      formulations of ferric trimaltol in a double-blind, cross-over, randomized study.
      The conventional colorimetric method for detecting serum iron was compared with
      thermal analyses after trichloroacetic acid (TCA) treatment of serum.
      Measurements of serum iron levels by TCA treatment and thermal analysis closely
      agreed with measurements by colorimetry. For all formulations, serum iron levels
      peaked at 90 min with a plateau of at least 5 h [mean (standard deviation) peak
      absorption 8.3% (6.3%) of ingested dose, n=48]. Absorption of iron, based on peak
      serum values or area under the serum curve, was not different for the four
      formulations (n=12 each) and correlated with the individual's iron status, as
      assessed by serum ferritin values (r = -0.6; P < 0.001). Normal colorimetry is
      suitable for analysis of serum iron levels following ingestion of ferric
      trimaltol. There is rapid and sustained absorption of iron from ferric trimaltol
      and, as with ferrous iron, uptake appears to be controlled through normal
      mechanisms of iron acquisition that depend upon body iron stores.

PMID- 10902862
TI  - Cost-effective strategy for the serological investigation of coeliac disease.
AB  - Increased numbers of requests for serological investigation of coeliac disease,
      and a local trend to request both anti-gliadin antibodies (AGA) and anti
      endomysium antibodies (AEA) simultaneously, resulted in cost pressures that
      prompted a review of our practice. Serology results from all patients (771
      children, 511 adults) investigated for coeliac disease over a 3-year period were
      compared with small intestine histology where available. IgG AGA and IgA AGA were
      measured by enzyme-linked immunosorbent assay (in-house), IgA AEA by
      immunofluorescence (send-away contract). Overall diagnostic performance was as
      follows: AGA sensitivity 84%, specificity 88%, positive predictive value (PPV)
      24%, negative predictive value (NPV) 99%; AEA sensitivity 88%, specificity 97%,
      PPV 65%, NPV 99%. Results showed AGA, with its high NPV, to be a suitable first
      line test to exclude coeliac disease. The high specificity of AEA makes it a
      suitable confirmatory test when AGA is positive. Introduction of this step-wise
      approach to coeliac disease investigation resulted in cost savings of at least
      Pound Sterling 5000 per year without detriment to the clinical service.

PMID- 10902863
TI  - Detection of LDL receptor by ligand blotting with chylomicron remnants labelled
      with colloidal gold.
AB  - The LDL receptor plays a pivotal role in the clearance of pro-atherogenic
      lipoproteins, and LDL receptor deficiency may be the underlying cause of several
      primary and secondary dyslipidaemic conditions. Intervention strategies are often
      targeted to increase hepatic LDL receptor expression. It is difficult to
      quantitate hepatic LDL receptor activity and to monitor changes post-therapy. In
      order to avoid liver biopsy, human skin fibroblasts or circulating mononuclear
      cells have often been used as surrogate markers for the hepatic receptor.
      Fibroblasts, and particularly mononuclear cells, are relatively easy to isolate
      and can be stored for extensive lengths of time without significant loss of LDL
      receptor expression. Leucocytes or fibroblasts are normally probed with
      isotopically or gold-labelled LDL. However, the specific activity of the LDL
      conjugate is usually too low to enable accurate quantitation of differences, or
      changes, in LDL receptor expression. In this study, we describe an enhanced
      colloidal gold-labelling procedure for the detection of LDL receptor binding
      activity. The binding of colloidal gold-labelled chylomicron remnants to human
      hepatocytes (HepG2 cells) was compared with that of gold-conjugated LDL. Labelled
      remnants bound specifically to a cell surface protein with a molecular weight of
      approximately 130 kDa. Binding was blocked in the presence of unlabelled
      remnants, LDL, or antiserum specific to the LDL receptor. The binding of gold
      labelled remnants was substantially greater than that of gold-labelled LDL.
      Compared with gold-labelled LDL, we found a much clearer demarcation of remnant
      binding with hepatocytes incubated in the presence or absence of sterols. Our
      observations suggest that, because of the greater affinity of the LDL receptor
      for lipoproteins containing apolipoprotein E, changes in LDL receptor expression
      might be more readily identified using gold-labelled remnants. We conclude that
      gold-conjugated chylomicron remnants might provide a useful means of detecting
      subtle changes in LDL receptor expression.

PMID- 10902864
TI  - Dual HDL/total cholesterol test: a single-tube, homogeneous assay for sequential
      measurement of HDL cholesterol and total cholesterol.
AB  - The quantitation of cholesterol in lipoprotein subfractions is valuable in
      estimating the risk for coronary artery disease, but requires multiple tests. We
      describe a relatively simple procedure, referred to as the dual HDL/total
      cholesterol (DHT) assay, which allows the sequential measurement of HDL
      cholesterol (HDL-C) and total cholesterol (total-C) in a single tube. HDL-C is
      first measured using a homogeneous assay that utilizes an anti-apolipoprotein B
      [apo(B)] antibody, which sterically blocks the enzymatic measurement of
      cholesterol on the non-HDL subfractions. Next, deoxycholate is added, which
      disrupts the antibody-apo(B) complex and allows the subsequent enzymatic
      measurement of the remaining cholesterol in the non-HDL subfractions. The DHT
      assay has an acceptable analytical performance and yields results similar to
      standard methods: for HDL-C, y(DHT) = 0.98x + 0.19, r=0.90; for total-C, y(DHT) =
      1.11x - 0.09, r=0.99. In summary, the DHT assay is a homogeneous assay for both
      HDL-C and total-C, and provides a simple and cost-effective method for screening
      for hyperlipidaemia.

PMID- 10902865
TI  - Antioxidant vitamin concentrations and LDL oxidation in nephrotic syndrome.
AB  - The increased risk of atherosclerosis in nephrotic syndrome is attributable in
      part to the associated hyperlipidaemia. The importance of oxidation of LDL in the
      atherogenic process has been recognized over the last 15 years. However, there
      are few data on the balance of antioxidant defences and lipoprotein oxidation in
      nephrotic syndrome. Plasma antioxidant vitamin concentrations and indices of LDL
      oxidation (LDL lipid hydroperoxide content and the susceptibility of LDL to
      oxidation) were measured in two groups of patients; group I comprised 29
      nephrotic patients and group II comprised 25 patients with haematuria. Plasma
      ascorbate concentration was significantly lower in group I (the nephrotic group)
      compared with group II (median 13.3 versus 22.2 micromol/L; P<0.001). Vitamin E
      concentrations were higher in group I but were not significantly different if
      corrected for total plasma cholesterol (6.12 versus 5.88 micromol/mmol; P=0.33).
      However, these changes resulted in a low ascorbate:vitamin E ratio in group I
      (0.19 versus 0.87; P<0.0001). Despite these changes in important antioxidant
      vitamin concentrations, we were unable to demonstrate any increased
      susceptibility to LDL oxidation in vitro or any difference in LDL lipid
      hydroperoxide content. These data suggest that there may be a relative defect of
      oxidant/antioxidant balance in nephrotic syndrome which could predispose to
      increased oxidative stress. However, measures of LDL oxidation were not
      significantly different between the two groups. LDL was protected from oxidation
      despite the severe hyperlipidaemia and the low circulating vitamin C
      concentrations.

PMID- 10902866
TI  - Measurement of glycated haemoglobin in whole blood by a novel fluorescence
      quenching assay.
AB  - We describe a method for the specific measurement of glycated Hb (GHb) by
      fluorescence quenching. Whole blood is added to lysing solution, then the lysate
      is mixed with eosin-boronic acid solution and reacted for at least 5 min at room
      temperature. The quenching of the fluorescence of the eosin-boronic acid solution
      is proportional to the concentration of GHb present. Total Hb concentration was
      measured by absorbance and the GHb expressed as a percentage of the total Hb.
      Comparison with a commercial high-performance liquid chromatography (HPLC) system
      for HbA1c showed: %GHb=1.30 (SD 0.04) %HbA1c + 1.36 (SD 0.30), S(y/x) 0.803,
      n=95, r=0.965 (SD=standard deviation). Intra-assay coefficients of variation were
      <2.5% (for GHb concentrations in the range 6-20%) and inter-assay coefficients of
      variation were <4.1% (10 assays on six samples with GHb concentrations in the
      range 6-20%). Linearity of response was demonstrated by dilution. The effect of
      adding exogenous glucose, bilirubin and triglycerides was tested on samples with
      low, medium and high GHb concentrations. No significant interference was found.
      Variation of haematocrit over the range 0.4-0.6 also had no significant effect on
      percentage GHb. Preliminary results with samples containing variant Hb (HbAS and
      HbAC) indicated good agreement with HPLC for these samples also.

PMID- 10902867
TI  - Glycated apolipoprotein A-I assay by combination of affinity chromatography and
      latex immunoagglutination.
AB  - The degree of glycation of plasma apolipoprotein A-I was measured by a
      combination of gel filtration, boronate affinity chromatography and latex
      immunoagglutination. The plasma concentrations of apolipoprotein A-I determined
      by this combination method (y) correlated well with those determined by
      turbidimetric immunoassay (x) (y=1.12x + 1.9, r=0.964). The inter- and intra
      assay coefficients of variation in the glycated apolipoprotein A-I assay were 4.1
      5.0% and 4.0-4.4%, respectively. Interference from plasma glucose at
      concentrations up to 55.1 mmol/L was eliminated by gel filtration. Labile
      glycated apolipoprotein A-I did not interfere with the measurement of glycated
      apolipoprotein A-I. Reference values for glycated apolipoprotein A-I were
      determined to be 2.4-4.0% (n=140), with no significant difference between men and
      women. The mean concentration of plasma glycated apolipoprotein A-I in patients
      with uncontrolled diabetes mellitus (5.11%) was significantly higher than in
      normal subjects (3.12%, P<0.001). The method is simple, rapid and highly
      sensitive for determination of the glycation level of plasma apolipoprotein A-I.

PMID- 10902868
TI  - Serum expression of sialyltransferase in normal and Down's syndrome-affected
      pregnancy.
AB  - Human chorionic gonadotrophin (hCG) has been used as a serum biochemical marker
      of Down's syndrome (DS) pregnancies, and recent studies have reported an increase
      in a hyperglycosylated form of the protein associated with DS. In the present
      study, the activity of the combined soluble serum sialyltransferase (ST) enzymes
      was examined as a potential marker for the hyperglycosylated form of hCG. There
      were no changes in total ST activity during the course of the pregnancy in normal
      mothers and there was no difference in enzyme activity in the DS pregnancies when
      compared with controls. These results suggest that, although there may be an
      alteration in the activities of one or more of the glycosyltransferase enzymes in
      the placenta resulting in an alteration in hCG glycosylation, this is not
      reflected in the serum soluble enzyme activity.

PMID- 10902869
TI  - Lactulose-mannitol intestinal permeability test: a useful screening test for
      adult coeliac disease.
AB  - The aim of this study was to determine the value of the lactulose mannitol
      intestinal permeability test in screening the general adult population for
      unrecognized enteropathy and latent coeliac disease. Subjects with positive
      serology (identified by screening carried out by the Belfast MONICA Project)
      along with controls were followed-up after 3 years and classified as having
      transient serology, persistent serology or coeliac disease. A 5-h urine
      collection was performed following the ingestion of 5 g lactulose, 2 g mannitol
      and glucose as an osmotic filler. Urinary concentrations of lactulose and
      mannitol were measured by enzymatic analysis. Percentage lactulose excretion
      (%LE) (0.94 versus 0.31, P<0.001) and lactulose mannitol excretion ratio (LMER)
      (0.12 versus 0.02, P<0.001) were significantly higher in screening-detected
      coeliac disease subjects compared with MONICA controls. The sensitivity of the
      permeability test was 87% in the screening situation compared with 81% in the
      clinical situation. In subjects with persistent and transient serology the LMER
      did not differ significantly from that of controls. The lactulose-mannitol test
      is a useful test for screening the general adult population for coeliac disease.
      Subjects with persistent and transient serology did not differ from MONICA
      controls and are unlikely to have latent coeliac disease.

PMID- 10902870
TI  - Measurement of urinary free cortisol using the Acs:180 serum cortisol
      chemiluminescent immunoassay.
AB  - Measurement of urinary free cortisol using the Bayer Automated Chemiluminescent
      System (ACS:180 PLUS) was evaluated and compared with an in-house extraction
      radioimmunoassay (RIA). Inter-assay coefficients of variation were acceptable,
      being respectively 5.3%, 4.8% and 3.8% at 141, 406 and 942 nmol/L (n=20) for the
      ACS direct assay and 19.4% and 12.1% at 27 and 116 nmol/L with dichloromethane
      extraction (n=10). Using tritiated cortisol, mean extraction efficiency for the
      ACS extraction protocol was 89% compared with 104% for the RIA method (n=6,
      P<0.001) and using urine spiked with ACS serum calibrator, extraction efficiency
      was only 76% (standard deviation 8.8%, n=49) on the ACS. Urine spiked with
      cortisol dissolved in ethanol also gave significantly lower recoveries on the ACS
      for both direct and extraction methods compared with the RIA. Regression analysis
      of results from a mixture of control serum samples and samples from patients
      (n=93) showed good correlations between the direct and extraction ACS methods and
      the RIA extraction assay. The median concentration in 23 normal subjects and 95%
      reference intervals (nmol/24 h) were: ACS direct, 237 (135-505); ACS extraction,
      91 (33-239); and RIA extraction, 146 (80-334). 5Beta-dihydrocortisol was the only
      major interferent in all assays. The ACS extraction assay showed acceptable
      performance and correlated well with the extraction RIA, although there was
      evidence of matrix-dependent effects causing low recovery.

PMID- 10902871
TI  - Measurement of iohexol by capillary electrophoresis: minimizing practical
      problems encountered.
AB  - Iohexol is a non-ionic contrast agent, which has been widely described in recent
      literature as an accurate marker for the measurement of glomerular filtration
      rate (GFR). Our aim was to establish a capillary electrophoresis assay, based on
      a previously described method, that had adequate reproducibility to be used as
      part of a clinical trial. In this paper, we examine the practical aspects,
      pitfalls and steps we took to achieve a precise and reproducible assay. To
      minimize laboratory variation, we examined properties such as the use of an
      internal standard in a capillary electrophoresis separation, alternative
      deproteinization methods for serum, the most suitable matrix for the dilution of
      standards and the implementation of suitable quality control material to ensure
      that run-to-run variability was minimized. The optimized capillary
      electrophoretic assay of iohexol was found to be robust, with over 860 runs from
      the one capillary over a 9-month period. Excluding capital costs of the
      instrument, the consumable cost of the assay is less than A$0.25 per test, with a
      run time of 5.25 min and a coefficient of variation (CV) of 4.3% at 80 mg/L. The
      GFR, calculated from the plasma clearance, had a reproducibility of 5.47%.

PMID- 10902872
TI  - Plasma apolipoprotein(b) to LDL cholesterol ratio as a marker of small, dense
      LDL.

PMID- 10902873
TI  - Recycling of deuterium from dideuterated glucose during moderate exercise.

PMID- 10902874
TI  - Aminoglycoside-induced metabolic abnormalities.

PMID- 10902875
TI  - Elevated serum CA-125 concentrations due to expression by a diffuse large B-cell
      lymphoma.

PMID- 10902876
TI  - Standardization of HbA1c measurements: a consensus statement.

PMID- 10902877
TI  - New antiepileptic drugs.

PMID- 10902878
TI  - Diagnostic dilemmas in Cushing's syndrome.

PMID- 10902880
TI  - Measuring trunk motions in industry: variability due to task factors, individual
      differences, and the amount of data collected.
AB  - The focus of this study was to determine the amount of data needed to ensure
      sufficient accuracy in estimating mean trunk motions of employees performing
      industrial manual materials handling tasks. Over 450 tasks were selected, in
      which the load weight and the vertical start and destination heights of the
      activity remained constant throughout the task. Data were collected as employees
      did their work at the job site, using the Lumbar Motion Monitor. Variance
      components were estimated in a hierarchical design and used to compute standard
      errors of mean trunk kinematic measures. These analyses found task-to-task
      variation to be much larger than the variability due to either multiple employees
      performing the same task or to repetitive movements within a task. Also, it was
      found that no significant reduction in the standard errors occurred when data
      were gathered for more than three employees and three repetitions of each task by
      an employee. This study indicates that the vast majority of variability in mean
      trunk motions is accounted for by the design of work tasks, and variations due to
      repeated cycles of a task or to employees are rather minor. It is also important
      as a basis for future work on modelling low-back disorder risk based on a job's
      trunk kinematic measures.

PMID- 10902879
TI  - Metabolic cost and subjective assessment of palletizing and subsequent recovery.
AB  - Twenty-one male blue collar workers repeatedly lifted (palletized) a box weighing
      22 kg six times min(-1) for 5 min to a shelf of fixed height. The experimental
      conditions included two planes of lifting (symmetries), two shelf clearances, and
      three headrooms. The metabolic (heart rate, caloric cost and ventilation volume)
      and psychophysical variables (rate of perceived exertion, RPE; visual analogue
      score, VAS; and body part discomfort ratings, BPDR) were measured during resting,
      palletization, and recovery phases. In palletization the heart rate and metabolic
      cost ranged between 25 to 35% of the maximal aerobic capacity. Of the three
      factors only headroom had a significant effect on metabolic cost (p<0.02) and the
      BPDR for low back (p<0.05). In the recovery phase only headroom had significantly
      effect (p<0.001) on metabolic cost. The metabolic recovery took 10 min; however,
      recovery measured through psychophysical indices appeared to continue for 20 min.

PMID- 10902881
TI  - Text entry on handheld computers by older users.
AB  - Small pocket computers offer great potential in workplaces where mobility is
      needed to collect data or access reference information while carrying out tasks
      such as maintenance or customer support. This paper reports on three studies
      examining the hypothesis that data entry by older workers is easier when the
      pocket computer has a physical keyboard, albeit a small one, rather than a touch
      screen keyboard. Using a counter-balanced, within-subjects design the accuracy
      and speed with which adults over 55 years of age could make or modify short text
      entries was measured for both kinds of pocket computer. The keyboard computer was
      the Hewlett Packard 360LX (HP), but the touch-screen computers varied across
      studies (experiment 1: Apple Newton and PalmPilot; experiment 2: Philips Nino;
      experiment 3: Casio E10). All studies showed significant decrements in accuracy
      and speed when entering text via the touch-screen. Across studies, most
      participants preferred using the HP's small physical keyboard. Even after
      additional practice with the touch screen (experiments 2 and 3) many entries
      still contained errors. Experiment 3 showed that younger people were faster but
      not more accurate than older people at using the touch-screen keyboard. It is
      concluded that satisfactory text entry on palm-size computers awaits improvements
      to the touch-screen keyboard or alternative input methods such as handwriting or
      voice. Interface developments that assist older people typically benefit younger
      users too.

PMID- 10902882
TI  - Effects of load carriage on heart rate, blood pressure and energy expenditure in
      children.
AB  - Fifteen male primary school children, aged 10 years, were selected to carry
      school bags of 10, 15 and 20% of their own body weights, where 0% body weight was
      used as a control. Maximum oxygen uptake (VO2max) tests were conducted on a
      motorized treadmill using a continuous incremental protocol. During the load
      carrying test, subjects walked on a treadmill at 1.1 m s(-1) for 20 min at each
      load condition. Blood pressures were measured before, immediately following, and
      at 3 and 5 min after every trial. Heart rate and expired VO2 were recorded
      before, during and 5 min after walking using a cardiopulmonary function system.
      The results showed a significant difference in oxygen uptake, energy expenditure
      and the recovery of blood pressure rise for between 10 and 20% body weight load
      conditions. The carrying weight of a school bag for children could be recommended
      as 10% of body weight because it was not significantly different from 0% load in
      the metabolic cost.

PMID- 10902883
TI  - Physical fitness of young women: carrying simulated patients.
AB  - An evaluation of physical fitness prior to employment appears to be mandatory for
      several occupations in order to protect the employee from overburdening and the
      employer from placing excess demands on the employee. One such occupation seems
      to be that of the field medical specialist who needs special physical strength
      since terrain conditions deny wheel-assisted transport of stretcher patients. The
      anthropometric and isometric force data of a total of 62 female and 48 male
      recruits for the medical service of the Bundeswehr were evaluated, together with
      their ability to carry a patient on a stretcher (weight = 14 kg) within a
      gymnasium. Initially the 'casualties' were simulated by sandbags weighing 60, 70,
      80 and 90 kg each on stretchers; subsequently equivalent-weight water cans were
      used. The tests were administered at the beginning and at the end of the general
      Basic Military Training (BMT). While all males were able to carry the simulated
      90 kg patient, only 22 out of 62 female recruits were able to do so at the
      beginning of BMT. At the end, the number had improved to 29 out of 55 women
      soldiers completing training. At the beginning of BMT 22.5% of the women soldiers
      were unable to rescue a simulated 70 kg patient; at the end of BMT the number had
      fallen to 18%. The isometric force values as measured revealed the hand grip
      strength as the best predictor for the capacity to carry simulated 90 kg
      patients. It is, therefore, suggested that a hand strength test be administered
      prior to field medical specialist training in order to channel unsuitable
      candidates into other training schemes.

PMID- 10902884
TI  - Predicting the vertebral inclination of the lumbar spine.
AB  - The objectives of this study were to examine the accuracy of the external stick
      marker method in the assessment of sagittal plane vertebral inclination (L1 to
      S1) during trunk flexion and to develop regression equations for predicting
      vertebral inclinations of the lumbar spine. Lateral radiographs of 16 subjects
      were taken from the upright position to a trunk flexion of 90 degrees, in 30
      degrees increments. Each subject was radiographed in only three of the four torso
      positions to minimize the risks of radiation. The inclinations of the vertebrae
      in the radiographic view were then obtained. The results show that the stick
      marker technique is a poor protocol for measuring vertebral inclination of the
      lumbar spine. During trunk flexion, the upper vertebrae incline linearly and the
      lower vertebrae incline exponentially. This is verified by the finding that the
      best-fit equations selected by regression techniques were linear at the upper
      vertebrae (L1, L2 and L3) and non-linear at the lower ones (L4, L5 and S1), with
      a mean R2 value of 0.964. The inherent difference in motion pattern between the
      vertebrae of the lumbar spine during trunk flexion is discussed for clinical and
      ergonomic purposes.

PMID- 10902885
TI  - Effects of upper respiratory tract illnesses on mood and performance over the
      working day.
AB  - The present study examined whether volunteers with common colds showed
      impairments in objective and subjective indicators of alertness over the course
      of the working day. All the volunteers (n = 21) were tested when healthy to
      provide baseline data for simple and choice reaction time tasks, visual search
      tasks and ratings of mood. These measures were taken before work (08.30 hours),
      at lunchtime (13.00) and after work (17.30). When participants developed a cold
      (n = 6) they repeated the procedure. Volunteers (n = 15) who remained healthy
      were recalled as controls and also repeated the procedures. The results showed
      that those with colds had significantly slower simple and choice reaction times,
      and felt less alert, more tense and less sociable. The effects of having a cold
      on simple reaction time, alertness and anxiety increased over the day. This
      extends earlier research and shows that some of the effects of upper respiratory
      tract illnesses on mood and performance will depend on when assessments are made.
      These results also imply that performance and well-being at work will be impaired
      by upper respiratory tract illnesses.

PMID- 10902886
TI  - Dual displays.
AB  - The study examined whether the simultaneous presentation of different map
      displays can aid situational awareness in spatial tasks relying on ego-centred
      and world-centred reference frames. Two commonly used aircraft displays, track-up
      and north-up maps, were compared with a dual aircraft display consisting of both
      track-up and north-up maps. Participants took part in two tasks: one relied on an
      ego-centred reference frame (ERF) and the other on a world-centred reference
      frame (WRF). The ERF task involved left/right judgements with respect to the
      aircraft's current heading while in the WRF task participants were asked to
      identify the compass heading associated with a landmark. A moderate amount of
      training resulted in a significant improvement with the dual maps in both the WRF
      task (relative to track-up maps) and the ERF task (relative to north-up maps).
      The findings are discussed with reference to how attention is allocated to visual
      displays.

PMID- 10902887
TI  - Qualitative models of seat discomfort including static and dynamic factors.
AB  - Judgements of overall seating comfort in dynamic conditions sometimes correlate
      better with the static characteristics of a seat than with measures of the
      dynamic environment. This study developed qualitative models of overall seat
      discomfort to include both static and dynamic seat characteristics. A dynamic
      factor that reflected how vibration discomfort increased as vibration magnitude
      increased was combined with a static seat factor which reflected seating comfort
      without vibration. The ability of the model to predict the relative and overall
      importance of dynamic and static seat characteristics on comfort was tested in
      two experiments. A paired comparison experiment, using four polyurethane foam
      cushions (50, 70, 100, 120 mm thick), provided different static and dynamic
      comfort when 12 subjects were exposed to one-third octave band random vertical
      vibration with centre frequencies of 2.5 and 5.5 Hz, at magnitudes of 0.00, 0.25
      and 0.50 m x s(-2) rms measured beneath the foam samples. Subject judgements of
      the relative discomfort of the different conditions depended on both static and
      dynamic characteristics in a manner consistent with the model. The effect of
      static and dynamic seat factors on overall seat discomfort was investigated by
      magnitude estimation using three foam cushions (of different hardness) and a
      rigid wooden seat at six vibration magnitudes with 20 subjects. Static seat
      factors (i.e. cushion stiffness) affected the manner in which vibration
      influenced the overall discomfort: cushions with lower stiffness were more
      comfortable and more sensitive to changes in vibration magnitude than those with
      higher stiffness. The experiments confirm that judgements of overall seat
      discomfort can be affected by both the static and dynamic characteristics of a
      seat, with the effect depending on vibration magnitude: when vibration magnitude
      was low, discomfort was dominated by static seat factors; as the vibration
      magnitude increased, discomfort became dominated by dynamic factors.

PMID- 10902888
TI  - Quantitative prediction of overall seat discomfort.
AB  - Static seat characteristics (seat stiffness) and dynamic seat characteristics
      (vibration magnitude) can both influence judgements of seat comfort. It is
      proposed that seat comfort can be predicted on the basis of Steven's
      psychophysical law: psi = kphi(n), where psi is a sensation magnitude, phi is the
      stimulus magnitude and k is a constant. The law is modified to: psi = a +
      bphis[n(s)] + cphiv[n(v)], where phis and phiv represent seat stiffness and
      vibration magnitude, n(s) and n(v) are exponents determined by the rate of
      increase in discomfort associated with the stiffness and vibration magnitude, and
      a, b and c are constants. The stiffness of foam loaded to 490 N may indicate
      static seat comfort, while the vibration dose value (VDV) on the seat surface may
      indicate vibration discomfort. Two experiments with 20 subjects investigated this
      approach. The first experiment with five magnitudes of vibration, three foams and
      a rigid wooden flat seat yielded 0.929 for the exponent, n(v), for VDV. In the
      second experiment subjects judged the overall seat discomfort while exposed six
      vibration magnitudes with the same four seating conditions. This experiment
      yielded 1.18 for the exponent, n(s), for seat stiffness. The overall prediction
      of seat discomfort was given by: psi = -50.3 + 2.68phis1.18 + 101phiv0.929. The
      prediction equation provided more accurate estimates of subject discomfort than
      models using either the VDV alone or the stiffness alone, especially when the
      vibration magnitude was low or the seats were similar. An interaction variable
      between the VDV and the stiffness slightly improved the prediction. The
      equivalence of the two stimuli was given by log10 (stiffness) = 0.787 log10 (VDV)
      + 1.34, or log10 (VDV) = 1.27 log10 (stiffness) - 1.70.

PMID- 10902889
TI  - Evaluation of acoustic beacon characteristics for navigation tasks.
AB  - The goal of the present study was to investigate the human factors issues related
      to acoustic beacons used for auditory navigation. Specific issues addressed were:
      (1) the effect of various beacon characteristics on human accuracy in turning
      toward the direction of the acoustic beacon; (2) the difference between real and
      virtual environments on human accuracy in turning toward the acoustic beacon; and
      (3) the perceived sound quality of various acoustic beacons. Three experiments
      were conducted in which acoustic beacons were presented in a background of 80 dBA
      pink noise. Results of the localization tasks revealed that (a) presentation mode
      (continuous versus pulsed beacon sound) did not affect the overall localization
      accuracy or number of front-back confusion errors; and (b) the type of acoustic
      beacon affected the size of localization error. Results of the sound quality
      assessment indicated that listeners had definite preferences regarding the type
      of sound being used as a beacon, with (a) non-speech beacons preferred over
      speech beacons, (b) a beacon repetition rate of 1.1 rps preferred over either the
      0.7 or 2.5 rps rates, and (c) a continuous operation of a beacon preferred over a
      pulsed operation. Finally, sound quality ratings and localization errors were
      highly negatively correlated. This finding demonstrates the usefulness and
      practical values of sound quality judgements for audio display design and
      evaluation.

PMID- 10902890
TI  - Disparate effects of long-term potentiation on evoked potentials and single CA1
      neurons in the hippocampus of anesthetized rats.
AB  - To examine the effects of long-term potentiation (LTP) on individual neurons in
      the intact brain, anesthetized rats were implanted with a recording stereotrode
      in the right CA1 layer of the hippocampus and a stimulating electrode in the
      right and left CA3 layers. The evoked and spontaneous firing of single CA1
      neurons was characterized before and after LTP of the contralateral (commissural)
      Schaffer collaterals and again after LTP of the ipsilateral (associational)
      Schaffer collaterals. Individual CA1 neurons displayed either increases or
      decreases in evoked and spontaneous firing after LTP. As many as five
      discriminated cells were recorded simultaneously, and they typically responded
      discordantly, so that after LTP, firing in some neurons increased while in others
      it decreased. The response of individual neurons to in vivo LTP may be modulated
      by heterogeneous synaptic changes on individual and local groups of cells, and by
      changes in feed-forward excitation and inhibition provided by local hippocampal
      circuitry.

PMID- 10902891
TI  - Water maze and radial maze learning and the density of binding sites of
      glutamate, GABA, and serotonin receptors in the hippocampus of inbred mouse
      strains.
AB  - Correlations between the densities of ionotropic glutamate, GABA(A), and
      serotonin binding sites in the hippocampus of seven inbred mouse strains and
      strain-specific learning capacities in two types of maze were studied. Binding
      site densities were measured with quantitative receptor autoradiography. Learning
      capacities were determined in a water maze task as well as in spatial and
      nonspatial versions of an eight-arm radial maze. The densities of most binding
      sites differed significantly between the strains in the subfields of Ammon's horn
      (CA1 and CA3) and the dentate gyrus, except for serotonin binding sites in CA1.
      By comparing the different strains, significant receptor-behavioral correlations
      between the densities of the GABA(A) receptors and the activity-dependent
      behavior in the water maze as well as the spatial learning in the radial maze
      were found. The densities of D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone
      propionate (AMPA) and kainate receptors correlated positively with learning
      capacity in the spatial eight-arm radial maze. We conclude that hereditary
      variations mainly in AMPA, kainate, and GABA(A) receptor densities are involved
      in behavioral variations in spatial and nonspatial learning tasks.

PMID- 10902892
TI  - Dorsal hippocampal function in unreinforced spatial learning.
AB  - This study examined learning about the spatial environment by rats during a
      single 10 min period of exploration on an eight-arm radial maze. Because no
      specific behaviors were learned during this procedure, the existence of learned
      spatial information was inferred from its retarding effect on subsequent
      conditioned cue preference (CCP) learning on the same maze. Previous experiments
      have shown that this form of spatial learning, measured in this way, requires an
      intact fimbriafornix and functional N-methyl-D-aspartate receptors. However, in
      the present experiments, large neurotoxic lesions of the dorsal hippocampus that
      impaired win-shift learning failed to eliminate the retarding effect of
      exploration on CCP learning. This result was obtained in three independent
      replications. These findings fail to confirm the hypothesis that the hippocampus
      is involved in spatial learning when that learning occurs in the absence of
      reinforcers and does not produce any specific learned behaviors. Previous work
      showed that this form of "pure" spatial learning requires an intact fimbria
      fornix for acquisition but not for expression; the present findings suggest that
      the hippocampus is not required for either of these processes. The fimbria-fornix
      may interact with other temporal lobe structures in mediating this form of
      learning. The function of the hippocampus may be limited in some way to
      situations that involve reinforcers and/or situations in which specific behaviors
      are learned.

PMID- 10902893
TI  - Effect of melatonin on the regulation of proenkephalin and prodynorphin mRNA
      levels induced by kainic acid in the rat hippocampus.
AB  - The in vivo short-term effect of melatonin on kainic acid (KA)-induced
      proenkephalin (proENK) or prodynorphin (proDYN) mRNA, and on AP-1 protein levels
      in the rat hippocampus, were studied. Melatonin (5 mg/kg) or saline was
      administered intraperitoneally (i.p.) to rats 30 min prior to and immediately
      after i.p. injection of KA (10 mg/kg). Rats were sacrificed 1 and 3 h after KA
      injection. The proENK and proDYN mRNA levels were significantly increased 3 h
      after KA administration. The elevations of both proENK and proDYN mRNA levels
      induced by KA were significantly inhibited by the preadministration with
      melatonin. The increases of proENK and proDYN mRNA levels induced by KA were well
      correlated with the increases of c-Fos, Fra-2, FosB, c-Jun, and JunB protein
      levels, which were significantly increased 3 h after KA administration and
      effectively inhibited by administration with melatonin. In an electrophoretic
      mobility shift assay, both AP-1 and ENKCRE-2 DNA binding activities were
      increased by KA, which were also attenuated by the administration of melatonin.
      In addition, cross-competition studies revealed that AP-1 or ENKCRE-2 DNA binding
      activity was effectively reduced by the 50x unlabeled cross-competitor.
      Therefore, these data suggest that melatonin has an inhibitory role in KA-induced
      gene expression, such as proENK and proDYN mRNA expression, and this may be due
      to a reduction of KA-induced AP-1 or ENKCRE-2 DNA binding activity.

PMID- 10902894
TI  - Kainic acid-induced mossy fiber sprouting and synapse formation in the dentate
      gyrus of rats.
AB  - In the kainic acid (KA) model of temporal lobe epilepsy, mossy fibers (MFs) are
      thought to establish recurrent excitatory synaptic contacts onto granule cells.
      This hypothesis was tested by intracellular labeling of granule cells with
      biocytin and identifying their synaptic contacts in the dentate molecular layer
      with electron microscopic (EM) techniques. Twenty-three granule cells from KA
      treated animals and 14 granule cells from control rats were examined 2 to 4
      months following KA at the light microscopic (LM) level; four cells showing MF
      sprouting were further characterized at the EM level. Timm staining revealed a
      time-dependent growth of aberrant MFs into the dentate inner molecular layer. The
      degree of sprouting was generally (but not invariably) correlated with the
      severity and frequency of seizures. LM examination of individual biocytin-labeled
      MF axon collaterals revealed enhanced collateralization and significantly
      increased numbers of synaptic MF boutons in the hilus compared to controls, as
      well as aberrant MF growth into the granule cell and molecular layers. EM
      examination of serially reconstructed, biocytin-labeled MF collaterals in the
      molecular layer revealed MF boutons that form asymmetrical synapses with
      dendritic shafts and spines of granule cells, including likely autaptic contacts
      on parent dendrites of the biocytin-labeled granule cell. These results
      constitute ultrastructural evidence for newly formed excitatory recurrent
      circuits, which might provide a structural basis for enhanced excitation and
      epileptogenesis in the hippocampus of KA-treated rats.

PMID- 10902895
TI  - Differential effects of the group II mGluR agonist, DCG-IV, on depolarization
      induced suppression of inhibition in hippocampal CA1 and CA3 neurons.
AB  - We investigated the role of metabotropic glutamate receptors in the mediation of
      depolarization-induced suppression of inhibition (DSI), using whole-cell
      electrophysiological techniques in rat hippocampal slice preparation. In a
      previous work, we showed that a retrograde signal travels from CA1 pyramidal
      cells to GABA interneurons and prevents them from releasing GABA for tens of
      seconds at 30 degrees C. The resulting suppression of inhibition is DSI. The
      retrograde signal appeared to be glutamate, or a glutamate analog, which acted on
      group I metabotropic receptors on the interneurons. It is not known if DSI occurs
      in hippocampal subregions besides CA1. If DSI does occur in other regions, it
      will be important to know if the role of metabotropic glutamate receptors
      (mGluRs) in mediating DSI is the same everywhere. The distribution of mGluR
      subtypes varies among hippocampal subregions. In the CA3 region, unlike CA1,
      group II mGluRs are prevalent. It was possible, therefore, that in CA3, the group
      II mGluRs would mediate DSI. We have begun to investigate these issues. We now
      report that: 1) DSI does occur in CA3. 2) Carbachol induces IPSC activity that
      can be recorded in CA1 and CA3a. This carbachol-induced activity can be reduced
      by the selective group II mGluR agonist, DCG-IV, and by DSI. 3) Evoked IPSCs in
      CA3a, but not in CA1, can be reduced by DCG-IV; hence the interneurons activated
      by carbachol may reside in CA3a. 4) Despite the group II mGluR agonist
      sensitivity of CA3a interneurons, DSI in this region is not affected by a group
      II mGluR antagonist, CPPG, and therefore does not appear to be mediated by group
      II mGluRs.

PMID- 10902896
TI  - Kainic acid induction of mossy fiber sprouting: dependence on mouse strain.
AB  - After seizures caused by kindling or kainic acid (KA), hippocampal granule-cell
      axons, the mossy fibers, sprout into the supragranular layer of the rat. The
      mechanisms underlying this phenomenon remain elusive, but excitotoxic loss of
      hilar cells, which project to this supragranular layer, is suspected to be a
      critical determinant. Consistent with this hypothesis, we previously reported
      that while rats show mossy fiber sprouting after kainate, ICR mice do not. This
      may be associated with the observation that ICR mice, unlike rats, do not appear
      to show hilar cell death after KA (McNamara et al., Mol Brain Res 1996;40:177
      187). Other strains of mice, however, such as 129/SvEMS, do show hilar cell death
      after KA (Schauwecker and Steward, Proc Natl Acad Sci USA 1997;94:4103-4108). We
      examined the possibility that the 129/SvEMS mouse strain would show granule-cell
      sprouting, in contrast to ICR mice. After administration of KA, mossy fiber
      sprouting was indeed observed in strain 129/SvEMS, but only in animals displaying
      evident hilar cell death. In contrast, neither hilar cell death nor mossy fiber
      sprouting was observed in ICR mice, confirming previous results. Both mouse
      strains demonstrated comparable behavioral seizures. These results strengthen the
      view that hilar cell death, together with epileptogenesis, triggers reactive
      synaptogenesis and mossy fiber sprouting.

PMID- 10902897
TI  - Estradiol induces a phasic Fos response in the hippocampal CA1 and CA3 regions of
      adult female rats.
AB  - Previous studies have shown that estradiol induces structural and functional
      changes in hippocampal CA1 pyramidal cells of the adult female rat. Estradiol
      increases the density of dendritic spines and axospinous synapses on CA1
      pyramidal cells, and increases these cells' sensitivity to NMDA receptor-mediated
      synaptic input. Curiously, while estradiol effects are observed in CA1 pyramidal
      cells, the majority of the evidence indicates that these cells lack genomic
      estradiol receptors. In contrast, genomic estradiol receptors are expressed in at
      least some hippocampal interneurons in CA1. The goal of the present study was to
      determine which hippocampal neuronal populations are activated by estradiol, as
      determined by induction of c-Fos immunoreactivity, as well as the time-course of
      this activation. We quantified c-Fos expression in each of the major subdivisions
      of the hippocampus in adult female rats at various time points during the same
      estradiol treatment regimen known to regulate dendritic spines and synapses on
      CA1 pyramidal cells. Our results show a phasic estradiol-induced c-Fos response
      in the pyramidal cell layers of both CA1 and CA3. c-Fos was induced within 2 h of
      treatment, decreased at 6 and 12 h, and subsequently increased again at 24 h
      after treatment with estradiol. Double labeling for c-Fos and GAD 65 or GAD 67
      suggests that c-Fos is induced primarily in principal cells, though a small
      proportion of GABAergic cells is also labeled. These estradiol-induced changes in
      c-Fos expression may reflect phasic neuronal activation and coupling to gene
      expression, which could be involved in estradiol's effects on excitatory synaptic
      connectivity in the hippocampus.

PMID- 10902898
TI  - Neurons in the hilus region of the rat hippocampus are depleted in number by
      exposure to alcohol during early postnatal life.
AB  - We have previously shown that exposing rats to a relatively high dose of ethanol
      during early postnatal life resulted in a deficit in spatial learning ability.
      This ability is controlled, at least in part, by the hippocampal formation. The
      purpose of the present study was to determine whether exposure of rats to ethanol
      during early postnatal life affected the number of specific neurons in the
      hippocampus. Wistar rats were exposed to a relatively high daily dose of ethanol
      between postnatal days 10 and 15 by placing them for 3 h each day in a chamber
      containing ethanol vapor. The blood ethanol concentration was about 430 mg/dl at
      the end of the exposure period. Groups of ethanol-treated (ET) rats, separation
      controls (SC), and mother-reared controls (MRC) were anesthetized and killed at
      16 days of age by perfusion with phosphate-buffered glutaraldehyde (2.5%). The
      Cavalieri principle was used to determine the volume of various subdivisions of
      the hippocampal formation (CA1, CA2+CA3, hilus, and granule cell layer), and the
      physical disector method was used to estimate the numerical densities of neurons
      within each subdivision. The total number of neurons was calculated by
      multiplying estimates of the numerical density with the volume. There were, on
      average, about 441,000 granule cells in the granule cell layer and 153,000 to
      177,000 pyramidal cells in both the CA1 and CA2+CA3 regions in all three
      treatment groups. In the hilus region, ET rats had about 27,000 neuronal cells.
      This was significantly fewer than the average of 38,000 such neurons estimated to
      be present in both MRC and SC animals. Thus, neurons in the hilus region may be
      particularly vulnerable to the effects of a high dose of ethanol exposure during
      early postnatal life.

PMID- 10902899
TI  - Age-related resistance to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid-induced hippocampal lesion.
AB  - This study compares the effects of acute alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA) administration in the hippocampus in adult (3
      months) and middle-aged (15 months) rats at 15 days postinjection. Injection of 1
      and 2.7 mM AMPA produced dose-dependent neurodegeneration, assessed by Nissl
      staining; a glial reaction shown by glial fibrillary acidic protein
      immunocytochemistry; and calcification, revealed by alizarin red staining.
      Furthermore, at both doses, these alterations were significantly greater in 3
      month-old rats. Finally, at AMPA 2.7 mM, no significant changes in the density of
      hippocampal parvalbumin- or calbindin-immunoreactive neurons or in choline
      acetyltransferase, glutamate uptake, or GABA uptake activities were found in 15
      month-old animals, whereas significant reductions in parvalbumin (-76%) and
      calbindin (-32%) immunostaining and in GABA uptake (-27%) were observed in 3
      month-old animals compared to the respective sham-operated or control animals. In
      conclusion, this study clearly demonstrates that in rats the vulnerability of
      hippocampal neurons and the glial and calcification reactions to AMPA-induced
      injury decreased with age between 3 and 15 months. Our results also indicate that
      hippocampal cholinergic, glutamatergic, and GABAergic systems show an adaptive
      response to excitotoxic damage in both adult and middle-aged animals.

PMID- 10902900
TI  - Early loss of interneurons and delayed subunit-specific changes in GABA(A)
      receptor expression in a mouse model of mesial temporal lobe epilepsy.
AB  - Unilateral injection of kainic acid (KA) into the dorsal hippocampus of adult
      mice induces spontaneous recurrent partial seizures and replicates
      histopathological changes observed in human mesial temporal lobe epilepsy (MTLE)
      (Bouilleret V et al., Neuroscience 1999; 89:717-729). Alterations in pre- and
      postsynaptic components of GABAergic neurotransmission were investigated
      immunohistochemically at different time points (1-120 days) in this mouse model
      of MTLE. Markers of GABAergic interneurons (parvalbumin, calbindin-D28k, and
      calretinin), the type-1 GABA transporter (GAT1), and major GABA(A)-receptor
      subunits expressed in the hippocampal formation were analyzed. Acutely, KA
      injection produced a profound loss of hilar cells but only limited damage to CA1
      and CA3 pyramidal cells. In addition, parvalbumin and calbindin-D28k staining of
      interneurons disappeared irreversibly in CA1 and dentate gyrus (DG), whereas
      calretinin staining was spared. The prominent GABA(A)-receptor alpha1 subunit
      staining of interneurons also disappeared after KA treatment, suggesting acute
      degeneration of these cells. Likewise, GAT1 immunoreactivity revealed
      degenerating terminals at 24 h post-KA in CA1 and DC and subsided almost
      completely thereafter. Loss of CA1 and, to a lesser extent, CA3 neurons became
      evident at 7-15 days post-KA. It was more accentuated after 1 month, accompanied
      by a corresponding reduction of GABA(A)-receptor staining. In contrast, DC
      granule cells were markedly enlarged and dispersed in the molecular layer and
      exhibited a prominent increase in GABA(A)-receptor subunit staining. After 4
      months, the dorsal CA1 area was lost almost entirely, CA3 was reduced, and the DG
      represented most of the remaining dorsal hippocampal formation. No significant
      morphological alterations were detected contralaterally. These results suggest
      that loss of hilar cells and GABAergic neurons contributes to epileptogenesis in
      this model of MTLE. In contrast, long-term degeneration of pyramidal cells and
      granule cell dispersion may reflect distinct responses to recurrent seizures.
      Finally, GABA(A)-receptor upregulation in the DG may represent a compensatory
      response persisting for several months in epileptic mice.

PMID- 10902901
TI  - Selectivity of the spatial learning deficit after lesions of the mammillary
      region in rats.
AB  - Rats with lesions of the mammillary region (MB-R) or a control group (C) were
      trained on a visual-spatial conditional associative learning task in which they
      had to learn to go to one of two locations depending on the particular visual cue
      presented on each trial; the rats approached the cues from different directions.
      The animals were subsequently tested on a spatial working memory task, the eight
      arm radial maze. Rats with damage to the MB-R were able to acquire the
      conditional associative task at a rate comparable to that of the C animals. By
      contrast, lesions of the MB-R led to a severe impairment on the radial maze. The
      present finding of a dissociation between the effects of MB-R lesions on two
      different classes of behavior suggest that the spatial learning deficit following
      damage of this region may be specific to remembering one or more places over a
      given time but not the ability to form associations between visual and spatial
      stimuli.

PMID- 10902902
TI  - fMRI activity in the medial temporal lobe during recognition memory as a function
      of study-test interval.
AB  - The phenomenon of temporally graded retrograde amnesia (loss of information
      acquired before the onset of amnesia) suggests that the hippocampus, and possibly
      other medial temporal lobe (MTL) structures, have a time-limited role in memory.
      In three experiments, we made a first attempt to use fMRI to assess activity in
      the hippocampal region (the CA fields of the hippocampus, the dentate gyrus, and
      the subiculum) and the adjacent parahippocampal gyrus (parahippocampal,
      entorhinal, and perirhinal cortices) during recognition memory testing as a
      function of study-test interval. Experiment 1 (n = 5) demonstrated activity in
      the hippocampal region and parahippocampal gyrus for targets relative to foils
      during recognition memory performance following a single study-test delay of
      about one-half hour. In Experiment 2, 15 participants studied line drawings at
      each of three different times prior to scanning: one-half hour, 1 day, and 1
      week. fMRI data were then collected during recognition memory testing, using
      targets from all three delays and foils. While an overall effect of targets vs.
      foils was found in both the hippocampal region and the parahippocampal gyrus,
      there was no effect of study-test interval on target activity. In Experiment 3 (n
      = 13), behavioral performance (reaction time and accuracy) was equated across the
      three delays. Again, no effect of study-test interval was observed. It is
      possible that the time span sampled in our study (one-half hour to 1 week) was
      too short to observe changes in activity. Alternatively, activity in the MTL
      during memory testing may occur even when these structures are not necessary for
      retrieval.

PMID- 10902903
TI  - Age-related deficits in the ability to encode contextual change: a place cell
      analysis.
AB  - Aging is known to impair the formation of episodic memory, a process dependent
      upon the integrity of the hippocampal region. To investigate this issue,
      hippocampal place cells were recorded from middle-aged and old F-344 male rats
      while running on a "figure-8" track. The top and bottom arcs of the track were
      removed, converting it into a plus maze, and the animals were required to conduct
      a working memory task. Following this change in task, the arcs were replaced and
      the animals again ran the figure-8 task. Analysis of place fields across the
      recording session demonstrated that both middle-aged and old rats had reliable
      representations of the figure-8 task. A comparison of place fields between
      different behavioral tasks (figure-8 and plus maze) demonstrated a change in the
      hippocampal representation of the environment in both age groups, despite the
      fact that the animals remained on the maze throughout the recording session.
      Notably, place cells in old animals were less affected by the change in task than
      those in middle-aged animals. The results suggest that hippocampal neurons
      reflect significant behavioral events within a given environment. Furthermore,
      the data indicate that age-related episodic memory deficits may result from
      decreased sensitivity of the hippocampal network to respond to meaningful changes
      in the environment.

PMID- 10902904
TI  - An ORF from Bacillus licheniformis encodes a putative DNA repressor.
AB  - The complete sequence of a reading frame adjacent to the endo-beta-1,3-1,4-D
      glucanase gene from Bacillus licheniformis is reported. It encodes a putative 171
      amino acid residues protein with either, low significant sequence similarity in
      data banks or the corresponding orthologue in the recently sequenced Bacillus
      subtilis genome. Computer analyses predict a canonical Helix-Turn-Helix motif
      characteristic of bacterial repressors/DNA binding proteins. A maxicells assay
      shows that the encoded polypeptide is expressed. A DNA-protein binding, assay
      performed by gel electrophoresis shows that the expressed protein specifically
      binds to Bacillus licheniformis DNA.

PMID- 10902905
TI  - Cloning of genes participating in aerobic biodegradation of p-cumate from
      Rhodopseudomonas palustris.
AB  - Rhodopseudomonas palustris utilizes p-cumate as a carbon source both under
      anaerobic light and aerobic dark conditions. A gene cluster was isolated whose
      sequence showed high homology to genes which have been implicated the degradation
      of p-cumate in Pseudomonas pitida. Seven structural genes coding for dioxygenase
      reductase, dihydroxy-dihydro dehydrogenase, and ring cleavage oxygenases were
      identified. A putative regulator and its possible recognition site was suggested
      on the basis of homology data. Mutant cells in which a kanamycin cassette was
      inserted into the dihydroxy-dihydro dehydrogenase gene could not grow aerobically
      on p-cumate. The mutation had no effect on growth using the para substituted
      benzoate derivatives 4-hydroxycinnamate, ferulate, protocatechuate, and 2,3,4
      trihydroxybenzoate as sole carbon source. Moreover, mutant cells showed a growth
      pattern similar to wild type cells grown on these compounds under
      photoheterotrophic anaerobic conditions. These data suggest that genes of this
      operon are involved specifically in aerobic dissimilation of p-cumate.
      Intermediate products of p-cumate degradation could be detected from extracts of
      Escherichia coli heterologously expressing the first 5 genes responsible for the
      first two steps of p-cumate degradation in R. palustris. Primer extension
      analysis revealed the transcription regulation of the gene cluster which could be
      induced with para methyl-, ethyl- and isopropyl (cumate) benzoates. This is the
      first report on genes involved in aerobic degradation of these compounds in
      photosynthetic bacteria.

PMID- 10902906
TI  - Cloning of a cDNA encoding cathepsin D from salamander, Hynobius leechii, and its
      expression in the limb regenerates.
AB  - Cathepsin D is a major lysosomal aspartic proteinase participating in the
      degradation or modification of intra- and extracellular matrix molecules, and its
      activity is known to increase in the process of tissue reorganization during the
      early phase of salamander limb regeneration. Here, we report the cloning of a
      salamander cathepsin D cDNA from Hynobius leechii and its expression profile in
      normal and retinoic acid (RA) treated limb regenerates. The gene expression of
      cathepsin D increased notably during the dedifferentiation stage and decreased
      gradually thereafter. Furthermore, RA that enhances dedifferentiation of
      regenerating salamander limb caused the elevation of cathepsin D expression both
      in terms of level and duration. These results suggest that cathepsin D plays
      important role(s) in the dedifferentiation process, and enhancement of cathepsin
      D expression might be closely related to RA-evoked pattern duplication.

PMID- 10902907
TI  - Fliih, the murine homologue of the Drosophila melanogaster flightless I gene:
      nucleotide sequence, chromosomal mapping and overlap with Llglh.
AB  - The Drosophila melanogaster flightless I gene is involved in cellularization
      processes in early embryogenesis and in the structural organization of indirect
      flight muscle. The encoded protein contains a gelsolin-like actin binding domain
      and an N-terminal leucine-rich repeat protein-protein interaction domain. We have
      cloned Fliih, the corresponding chromosomal gene from the mouse, and determined
      its nucleotide sequence (15.6 kb). The predicted Fliih protein of 1271 amino
      acids is 95% identical to the human FLII protein. Like the human gene, Fliih has
      29 introns, compared with 13 in C. elegans and 3 in D. melanogaster. Fluorescence
      in situ hybridization was used to map Fliih to Chromosome 11B. Fliih lies
      adjacent to Llglh, the mouse homologue of the D. melanogaster tumor suppressor
      gene lethal(2) giant larvae. The sequence of the genomic DNA in this area,
      combined with cDNA sequences, establishes that the 3' ends of the Fliih and Llglh
      transcripts overlap. The overlap region contains polyA signals for both genes and
      is conserved between human and mouse.

PMID- 10902908
TI  - The structure and expression of the Salmo salar Ran gene.
AB  - The Ran protein is a highly conserved GTPase factor of the Ras-family of
      proteins. It is involved in the transport of proteins and RNA through the nuclear
      pores. cDNA sequences of Ran genes from different organisms are available but no
      vertebrate genomic sequence as yet. We have isolated a genomic cosmid clone of
      the Ran1 gene of Atlantic salmon (Salmo salar) and found that the gene is about
      2.2 kb and has got 5 introns. Its gene structure was compared to those of
      Caenorhabditis elegans and Arabidopsis thaliana and one intron was found to be
      conserved in position. Two different Ran transcripts were identified in salmon,
      indicating that there are two Ran genes, Ran1 and Ran2. Both transcripts were
      found in all ten salmon tissues tested, though Ran1 to a higher degree.

PMID- 10902909
TI  - Isolation and analysis of three peroxide sensor regulatory gene homologs ahpC,
      ahpX and oxyR in Streptomyces viridosporus T7A--a lignocellulose degrading
      actinomycete.
AB  - Increased lignolytic peroxidase activity has been demonstrated with the addition
      of sublethal doses of toxic H2O2 in Streptomyces viridosporus T7A. Until now, the
      effect of H2O2 at the molecular level has not been well characterized. Here, for
      the first time we report the isolation and analysis of three peroxide-induced
      gene homologs from S. viridosporus T7A; ahpC and ahpX (encoding alkyl
      hydroxyperoxidase subunits) and oxyR (encoding oxygen stress regulatory protein).
      The genome organization of these stress related genes were found to be
      divergently adjacent to each other. The protein sequence analysis of the oxyR
      homolog revealed a helix-turn-helix DNA-binding motif characteristic to the LysR
      of regulatory proteins induced by H2O2. The nucleotide sequence analysis of the
      intergenic region between ahpC and oxyR revealed that they shared a core T-n11-A,
      a signature protein-binding region of LysR family members. Based on similarities
      in sequence analysis, genetic organization, and the induction of lignin
      peroxidase activity upon exposure to hydrogen peroxide, we hypothesize a peroxide
      induction mechanism for the regulation of oxidative lignin biodegradation by S.
      viridosporus, possibly via use of OxyR which is also involved in regulating the
      peroxide stress response in this actinomycete.

PMID- 10902910
TI  - Structure and chromosomal localization of the RAE28/HPH1 gene, a human homologue
      of the polyhomeotic gene.
AB  - The Polycomb group of (Pc-G) genes and trithorax group of genes are known to play
      a crucial role in the maintenance of the transcriptional repression state of Hox
      genes, probably through modification of the chromatin configuration. The
      rae28/mph1 gene is a mammalian homologue of the Drosophila polyhomeotic gene,
      which belongs to the Pc-G genes. As reported previously, we established mice
      deficient in the rae28/mph1 gene and showed that these homozygous animals
      displayed the developmental defects compatible with a human congenital disorder,
      CATCH22 syndrome. In this study we analyzed the structural organization of the
      human counterpart of the rae28/mph1 gene (RAE28/HPH1) and its processed
      pseudogene (psiPH), which are located on, respectively, human chromosome 12p13
      and 12q13. The HPH1 gene consists of 15 exons spanning approximately 26 kb and
      its structural organization is well conserved between mouse and human. These
      genetic information of the RAE28/HPH1 gene may provide an important clue for
      further examination of its involvement in human congenital disorders related to
      CATCH22 syndrome.

PMID- 10902911
TI  - Isolation and characterization of Na+/Ca2+ exchanger gene and splicing isoforms
      in mice.
AB  - The Na+/Ca2+ exchanger gene NCX1 is ubiquitously expressed in mammalian tissues,
      and encodes several isoforms through alternative RNA splicing. In this report, we
      describe the gene structure that gives rise to the multiple isoforms, and the
      tissue-specific expression of these isoforms in mice. The mouse NCX1 gene
      contains a cluster of six exons (A, B, C, D, E, and F) which encode a variable
      region in the large intracellular loop of the protein, as previously reported in
      rabbits and humans. Using reverse transcription-polymerase chain reaction (RT
      PCR), expression of the isoforms was examined in several tissues. We also
      identified a novel splice variant, which originate from exons A, C, D, and F.
      These findings provide new insights into the significance of the large repertoire
      of NCX1 isoforms.

PMID- 10902912
TI  - Cloning of the beta-actin gene from the European flounder (Platichthys flesus
      L.).
AB  - A genomic clone of the European flounder (Platichthys flesus L.) beta-actin gene
      was isolated from a genomic DNA library and sequenced. The beta-actin gene has a
      predicted open reading frame of 373 amino acids, that was found to have high
      homology (99.2-99.7% identical) with several other species.

PMID- 10902913
TI  - Nucleotide sequence of the internal transcribed spacers of ribosomal DNA in Picea
      abies Karst.
AB  - The nucleotide sequences of the internal transcribed spacers (ITS1 and ITS2) of
      ribosomal DNA from Picea abies are reported. Two types of ITS1 of 2784 bp and
      3271 bp long exist, whereas only one ITS2 type 238 bp long is present in this
      species. The shorter ITS1 is characterized by three shorter subrepeats: ssr1,
      ssr2 and ssr3, 221 bp, 227 bp and 226 bp long respectively. Between the ssr1 and
      ssr2 sub-repeats are inserted three longer sub-repeats: LSR1, LSR2 and LSR3, 480
      bp, 480 bp and 581 bp long respectively. The similarity between the three ssr
      range from 66% to 79% and between the three LSR range from 65% to 96%. At the end
      of the LSR3 a microsatellite of 14 CT elements is present. The longer ITS1 type
      is due to a duplication of the LSR1, most probably obtained by unequal crossing
      over and it has an identity of 97.3% with the shorter ITS1 type.

PMID- 10902914
TI  - Molecular cloning of mouse alpha-1,6-fucosyltransferase and expression of its
      mRNA in the developing cerebrum.
AB  - Complementary DNA encoding mouse alpha-1,6-fucosyltransferase (FUT) was cloned.
      The deduced primary structure consisted of 575 amino acids and had 96.0% and
      93.0% identity with alpha-1,6-FUT of human and porcine origin, respectively.
      Quantitative analysis of alpha-1,6-FUT mRNA expression during selected
      developmental stages of the cerebrum showed that the expression increased during
      later embryonic stages and was highest in the early postnatal stages (P1 to P7),
      after which it declined somewhat but still remained relatively high in the mature
      adult. The expression profile suggests important roles of FUT in the developing
      central nervous system.

PMID- 10902915
TI  - A tRNA pseudogene in the archaeon Methanococcus jannaschii.
AB  - While searching the first completely sequenced genome of the archaeon
      Methanococcus jannaschii for a small RNA gene, we discovered a 5' truncated gene
      of a transfer RNA (tRNA(Ser-UCR)) at position 334,431-334,486; including the CCA
      end that exactly matched the 3' terminal domain of the annotated M. jannaschii
      tRNA(Ser-UCR) gene located at position 303,992-304,081. This truncated tRNA gene
      covering 56 nucleotides (about 2/3) of the genuine tRNA represents, to the best
      of our knowledge, the first described tRNA pseudogene in the archaeal domain.

PMID- 10902916
TI  - Isolation and sequence analysis of repA from the incurable 90 MDA plasmid of
      Azospirillum brasilense.
AB  - An open reading frame encoding a protein of 312 amino acids was identified in an
      essential region of the 90 MDa plasmid of Azospirillum brasilense. The putative
      protein shows similarity with RepA proteins of plasmids of Sphingomonas
      aromacitovorans, Rhodotermus marinus, Chlorobium limicola and Bifidobacterium
      asteroides and with the RepA protein of the broad host range plasmid pSa. A
      putative helix-turn-helix motif was identified in the central part of the A.
      brasilense RepA protein. Analysis of the upstream and downstream region of the A.
      brasilense repA gene revealed the presence of eight 15-bp repeats, which can
      possibly function as iterons.

PMID- 10902917
TI  - Sequence analysis of the atp operon of Clostridium acetobutylicum DSM 792
      encoding the F0F1 ATP synthase.
AB  - The atp gene region of Clostridium acetobutylicum DSM 792 has been fully
      sequenced. It contains the F0F1 ATPase genes in the order atpIBEFHAGDC, whose
      products share high sequence homology to the respective proteins of a variety of
      other bacteria. It is the first such sequence available for a mesophilic
      Clostridium. Significant differences to other reported atp operons are a distal
      transcription start point 219 bp upstream of the translation start point and a
      second transcription initiation site (without corresponding promoter sequence)
      upstream of atpE, indicating posttranscriptional processing for massive
      expression of this gene product.

PMID- 10902918
TI  - A DNA fragment of Desulfovibrio gigas genome containing replication origin
      related genes.
AB  - The nucleotide sequence of a 10,772 base pair (bp) region from Desulfovibrio
      gigas genome was determined. This sequence, which is adjacent to the region
      containing the coding units for the metalloproteins rubredoxin-oxygen
      oxidoreductase (ROO) and rubredoxin, includes the flavodoxin gene. Additionally,
      it also contains four open reading frames (ORFs) related to genes frequently
      found in replication origin regions of prokaryotes. These hypothetical encoded
      polypeptides are: the response regulator proteins (PhoP and PhoR) from the
      phosphate regulon, a DNA partitioning protein and an asparagine synthetase.

PMID- 10902919
TI  - Cloning of cDNA encoding ethylene-responsive element binding protein-5 in the
      cultured cells of Nicotiana tabacum.
AB  - We have isolated a full-length cDNA clone from the cultured cells of Nicotiana
      tabacum, of which the deduced 225 amino acid sequence showed significant homology
      to the known ethylene-responsive element binding proteins (EREBPs) from tobacco
      and Arabidopsis. Although the clone shared substantial homology with an
      Arabidopsis ethylene-responsive element binding factor-3 (AtERF-3) throughout the
      full length, such a clone had not been found in N. tabacum cells yet; the clone
      was found to be 5th homologue of EREBPs on N. tabacum.

PMID- 10902920
TI  - Isolation of rat mitochondrial transcription factor A (r-Tfam) cDNA.
AB  - We have isolated rat mitochondrial transcription factor A (Tfam; formerly known
      as mtTFA) cDNA clones from a rat cerebellum cDNA library using human Tfam cDNA as
      a probe. The deduced amino acid sequence of r-Tfam shows 62% and 89% overall
      identity to human and mouse Tfam, respectively. We also show the presence of two
      r-Tfam isoforms in testis as for mouse. Our findings suggest that the mechanisms
      underlying transcription of mitochondrial genes are conserved among rat, mouse,
      and human.

PMID- 10902921
TI  - Complete cDNA sequence and amino acid analysis of a bovine ribonuclease K6 gene.
AB  - The complete cDNA sequence of a ribonuclease k6 gene of Bos Taurus has been
      determined. It codes for a protein with 154 amino acids and contains the
      invariant cysteine, histidine and lysine residues as well as the characteristic
      motifs specific to ribonuclease active sites. The deduced protein sequence is 27
      residues longer than other known ribonucleases k6 and shows amino acids exchanges
      which could reflect a strain specificity or polymorphism within the bovine
      genome. Based on sequence similarity we have termed the identified gene bovine
      ribonuclease k6 b (brk6b).

PMID- 10902922
TI  - Chromosome mapping and expression of human tip49 family genes.
AB  - TBP-interacting protein 49 (TIP49) was originally identified as a TBP-binding
      protein, and two related proteins are encoded by individual genes, tip49a and b.
      Although the function of this gene family has not been elucidated, they are
      supposed to play a critical role in nuclear events because they interact with
      various kinds of nuclear factors and have DNA helicase activities. At least,
      TIP49a has been suggested to act as an autoantigen in some patients with
      autoimmune diseases. In this study, we investigated the chromosome positions of
      this family of genes. Human tip49a and tip49b genes were mapped on 3q21 and
      19q13.2, respectively. Consistent with the notion that tip49 family genes are
      essential for cell growth, Northern blot analysis demonstrated that both genes
      are expressed ubiquitously in human tissues. It is worthy of notice that the
      testes contained large amounts of the both transcripts. These results are
      consistent with our previous results from tissue distribution analysis for of
      TIP49 proteins.

PMID- 10902923
TI  - Cloning and characterization of CIS 1b (cytokine inducible SH2-containing protein
      1b), an alternative splicing form of CIS 1 gene.
AB  - JAK-STAT pathway is essential in relaying cytokine signals and plays a vital role
      in cellular responses such as proliferation, differentiation and immunity. Some
      members of a recently found cytokine-inducible SH2 protein (CIS, =SOCS or SSI)
      family have proved to have negative effects on modulating JAK-STAT signaling
      pathway. In the present study, a novel human cDNA (CIS1b) which proved to be a
      variant of CIS1 gene was isolated by screen human placenta lambda gt11 cDNA
      library and 5'-rapid amplification of cDNA ends (RACE). Furthermore, the gene
      structure of CIS1 was determined by comparing the cDNA sequences of CIS1 and
      CIS1b to the genomic sequence in human chromosome 3p21.3. The expression patterns
      of CIS1b as well as CIS1 were analysed by Northern blot.

PMID- 10902924
TI  - Isolation and characterisation of a chick cDNA encoding the RNA polymerase common
      subunit RPB6.
AB  - The RPB6 cDNA of chicken, encoding one of the small subunits common to all three
      nuclear DNA-dependent RNA polymerases, has been isolated from an expression cDNA
      library by screening with a differential display derived probe, representing a
      gene shown to be highly up-regulated in early heart development. The nucleotide
      sequence of the cDNA isolated predicts a protein sequence of 127 amino acids.
      This sequence shares 124 amino acids (98% homology) with the human RNA polymerase
      II subunit 14.4 kDa (RPB6) and hamster hRPB6 and 123 amino acids (97% homology)
      with Rattus norvegicus RNA polymerase II subunit RPB6. Other conserved motifs in
      this protein and potential functions of RPB6 are discussed.

PMID- 10902925
TI  - Molecular cloning of canine and feline flt3 ligand reveals high degree of
      similarity to the human and mouse homologue but uniquely long cytoplasmic domain.
AB  - The cDNAs encoding canine and feline flt3 ligand (FL) have been isolated from
      libraries constructed from canine or feline peripheral blood mononuclear cells
      and sequenced. A full-length canine FL cDNA encodes a polypeptide of 294 amino
      acids that shares 52.8% and 71.0% identity with the mouse and human FL protein,
      respectively. While the feline FL cDNA encodes a polypeptide of 291 amino acids
      that shares 54.1% and 70.2% identity with the mouse and human FL protein,
      respectively. The canine and feline FL proteins share 82.8% identity at amino
      acid level. Besides those encoding the full-length FL protein, several
      alternatively spliced forms of canine FL transcripts were also isolated. The
      canine and feline FL proteins have longer cytoplasmic domain than their mouse and
      human homologue.

PMID- 10902926
TI  - Cloning and molecular characterization of hrpX from Xanthomonas axonopodis pv.
      citri.
AB  - The hrpX gene of plant pathogenic Xanthomonas species is essential for
      pathogenicity on host plants and to cause hypersensitive reaction on non-host
      plants. We cloned and analyzed a hrpX homologue, designated hrpXct, of X.
      axonopodis pv. citri, a pathogen of citrus canker. The open reading frame of
      hrpXct has 1431 bp in nucleotides which has a coding capacity of 476 amino acid
      residues with a molecular mass of 52.4 kDa. The predicted amino acid sequence of
      HrpXct has 90% identity to the AraC family type transcriptional activator protein
      HrpXc of X. campestris pv. campestris, 95% to HrpXo of X. oryzae pv. oryzae and
      97% to X. vesicatoria. These findings clearly indicate and confirm that the
      structure of the hrpX genes in plant pathogenic Xanthomonas species is highly
      conserved.

PMID- 10902927
TI  - Genomic structure of the 5' end of the porcine ryanodine receptor 3 gene (RYR3).
AB  - Ryanodine receptor 3 is a calcium channel located in the membrane of the
      endoplasmic reticulum. We isolated eight overlapping PAC clones from the porcine
      ryanodine receptor 3 gene (RYR3) and determined the DNA sequences of the first
      and second exon together with 5.8 kb of 5' flanking region and 10.3 kb of intron
      sequences. By comparing the porcine genomic sequence to the human RYR3 cDNA
      sequence the porcine transcription start site could be mapped to a GC-rich
      region. Physical mapping of the isolated PAC clones revealed that the complete
      porcine RYR3 gene spans more than 200 kb of genomic DNA.

PMID- 10902928
TI  - July 2000: extreme environments.

PMID- 10902929
TI  - Interaction of chemical defense clothing and high terrestrial altitudes on
      lift/carry and marksmanship performance.
AB  - BACKGROUND: The increased metabolic energy requirement imposed by a chemical
      defense uniform (CDU) and the lower maximal aerobic capacity associated with
      increased altitude should produce greater demands on the cardiopulmonary system
      during the performance of a given work task at increasing altitudes. We
      hypothesized that: a) relative to sea level, the decrements in physical work
      performance caused by ascending to high terrestrial altitudes would be greater in
      a CDU compared with a standard fatigue uniform (U.S. Army, BDU); b) the aversive
      subjective reactions to the CDU would be accentuated with increasing altitude;
      and c) that staging at moderate altitude, to induce acclimatization, would
      restore work performance at higher altitudes to sea level norms. METHODS: The
      physiological and subjective responses of 8 male soldiers to work (10-min lift
      and-carry task and rifle marksmanship) were measured. Subjects wore the BDU and a
      CDU ensemble (U.S. Army, BDO) at sea level, intermediate (2743 m) and high (4,300
      m) altitudes following rapid and staged (3 d at 1,830 m) ascents to the higher
      altitudes. RESULTS: Lift/carry task performance tended to be lower (p = 0.076) in
      the CDU vs. the BDU at altitude. The cardiopulmonary responses to the lift/carry
      task increased at altitude and were greater in the CDU. The subjects' perception
      of their ability to perform the lift/carry task at altitude was adversely
      impacted more in the CDU than the BDU. Rapid ascent to intermediate altitude
      degraded marksmanship in both uniforms. Following staged ascent, lift/carry task
      and marksmanship performance was restored to sea level norms. CONCLUSIONS:
      Personnel wearing CDU or equivalent protective clothing at intermediate to high
      terrestrial elevations should anticipate proportionally larger CDU-induced
      decrements of work performance and lower tolerance to working in a CDU than
      experienced near sea level. Staging at moderate altitude is an effective strategy
      for restoring work performance to sea level norms at higher altitudes.

PMID- 10902930
TI  - Effects of different stay durations on attentional performance during two
      mountain expeditions.
AB  - BACKGROUND: Hypoxia-induced deficits in intellectual performance are linked to
      the altitude level reached, the speed of the ascent and the time spent at high
      altitude. This study analyzes attentional changes during adaptation to two
      different types of stay at high altitude on two different expeditions: one
      involving a 16-d trip between 2,000 m and 5,600 m, followed by a 2-d ascent to
      6,440 m and back again; the other, a 21-d stay at 6,542 m. We tested the
      hypothesis that, at similar high altitudes, decrements in attentional performance
      would only occur during a long duration stay. METHODS: Indexes for attentional
      performance were calculated for two experimental groups under normoxia before the
      climb, under acute and chronic hypoxia during the climb, and under normoxia after
      the climb. They were compared for two control groups tested only under normoxia.
      RESULTS: The altitude stay was found to have an effect on the 6,542 m group when
      compared with the controls. Group performance differed at 2 d and 21 d after
      their arrival at 6,542 m and after their return to normoxia. When all the test
      administrations were pooled together for this expedition we noted an interaction
      between the level of difficulty of the task and the experimental and control
      groups: namely the difference between the groups was greater for the difficult
      task than it was for the easy task. No effect was found for the other expedition
      (at 5,600 m) when the group tested was compared with the controls. CONCLUSION:
      For a 21-d stay at an altitude of 6,542 m with the same ascent protocol as a
      group climbing to a lower altitude (16 d between 2,000 m and 5,600 m followed by
      a 2 d ascent to 6,440 m and back again), subjects appeared to suffer from
      attentional performance deficits which persisted for several days after the
      subjects returned to normoxic conditions.

PMID- 10902931
TI  - Effects of mountaineering training at high altitude (4,350 m) on physical work
      performance of women.
AB  - BACKGROUND: Little is known about work performance of women in hypobaric hypoxia.
      Moreover, whether native women of moderate altitude (2,000-2,100 m) differ from
      their lowland counterparts in their ability to adjust to hypobaric hypoxia is
      also not known. Hence, physiological alterations on work performance due to
      mountaineering training with altitude adaptation was evaluated in two groups of
      women and compared to the differences in the responses of the native women of
      moderate altitudes (Highlanders-HL) with those of the plains (Lowlanders-LL).
      METHODS: Pre-training tests were conducted at 2,100 m, then during sojourn to
      4,350 m and re-tested again after return to 2,100 m. Physical work performance
      was assessed following standard step-test-exercise on a 30 cm stool with 24
      cycles x min(-1) for 5 min. Heart rate, BP, ventilation, oxygen consumption and
      oxygen saturation were monitored at rest and during exercise followed by 5 min
      recovery in all three situations. RESULTS: During initial assessment, HL showed
      higher cardiovascular efficiency with faster recovery of exercise heart rate.
      Both groups showed significant improvement in physical performance due to
      mountaineering training at high altitude (HA). The difference in performance
      between two groups narrowed down at 4,350 m and further reduced during re-test
      with maintenance of initial superiority of the HL. CONCLUSIONS: a) Native women
      of moderate altitude (HL) are more fit compared with their plains counterparts
      (LL); b) All women achieved marked improvement in cardiovascular and respiratory
      efficiency as well as the step-test score due to intense mountaineering training
      at HA, and the rate of improvement in physical performance was higher in LL; c)
      Further, induction by trekking under progressive hypoxia coupled with rigorous
      mountaineering activity at HA merits in understanding better acclimatization and
      improved physical performance.

PMID- 10902932
TI  - The effect of staged decompression while breathing 100% oxygen on altitude
      decompression sickness.
AB  - INTRODUCTION: Space Shuttle extravehicular activity (EVA) requires decompression
      from sea level pressure (14.7 psia) to a 4.3 psia (30,300 ft) pressure suit. The
      transition currently involves altering the shuttle atmosphere to allow shirt
      sleeve denitrogenation to occur during a 12 to 36-h staged decompression (SD) at
      10.2 psia (9,800 ft) with an oxygen-enriched breathing gas (26.5% oxygen, 73.5%
      nitrogen). The denitrogenation provides protection from decompression sickness
      (DCS) during EVA in a 4.3 psia pressure suit. Our goal was to determine the
      highest altitude at which SD while breathing 100% oxygen (SD100) could provide
      effective protection from development of DCS symptoms after further decompression
      to 29,500 ft (4.5 psia). METHODS: There were 30 male subjects exposed to at least
      6 of 11 conditions in random order on successive months to 29,500 ft for 4 h
      while performing mild exercise and being monitored for venous gas emboli (VGE)
      with an echo-imaging system. The subjects received 15 min of ground-level (GL)
      preoxygenation and an additional 60 or 120 min of SD100 at one of four altitudes
      between 8,000 ft (10.9 psia) and 18,000 ft (7.3 psia). Control exposures followed
      a 75- or 135-min ground-level preoxygenation. RESULTS: During SD100, one case of
      DCS occurred at 18,000 ft, but not at lower staging altitudes. Higher levels of
      VGE were observed during SD100 at 18,000 ft than during SD100 at any lower
      altitude. CONCLUSION: Staged decompression at 16,000 ft and below results in
      decompression risk during subsequent decompression to 29,500 ft similar to that
      following equivalent periods of ground-level preoxygenation.

PMID- 10902933
TI  - A method for monitoring the health of US Navy submarine crewmembers during
      periods of isolation.
AB  - BACKGROUND: With the expansion of the manned space program, an essential
      consideration in planning is the medical support necessary for long-term
      missions. Information on analogous populations serving in isolated and/or
      contained environments may be useful in predicting health risks for astronauts.
      METHODS: The present study evaluates rates of health events that occur in a
      highly screened, healthy military population during periods of isolation. A
      centralized database was designed to collect medical encounter data from U.S.
      Navy submarines and contains demographic information, crew rosters for each
      patrol, medical encounter notes, accident reports, medical evacuation reports,
      vital signs and laboratory data. The population included in the present analysis
      is composed of crewmembers aboard 136 submarine patrols between January 1, 1997
      and December 31, 1998. RESULTS: A total of 2,044 initial visits to medical staff
      and 973 re-visits for the same condition were recorded during these patrols.
      Potentially mission-impacting medical events reported among crewmembers were rare
      (i.e., among a crew of 10 individuals, only 1-2 medical events would be expected
      to occur during a 100 d-mission). The most common category of medical events was
      injury, followed by respiratory illnesses (URIs), skin problems (minor
      infections, ingrown toenail), symptoms and ill-defined conditions, digestive
      disorders, infectious conditions, sensory organ problems (ear and eye), and
      musculoskeletal conditions.

PMID- 10902934
TI  - Orthostatic tolerance and hormonal changes in women during 120 days of head-down
      bed rest.
AB  - BACKGROUND: Women will be included as mission specialists in the upcoming
      International Space Station program. This paper describes the changes in volume
      regulating hormones and determines the degree of degradation in orthostatic
      tolerance in a group of women after 120 d of bed rest. The aim of this study was
      to test a countermeasure program to be used by women during long-duration
      spaceflights. METHODS: For 120 d of -6 degrees head-down bed rest (HDBR), eight
      healthy women were assigned either to a no-countermeasure (No-CM, n = 4), or to a
      countermeasure (CM, n = 4) group. In the countermeasure group, exercise began
      after 2 wk, pharmacological agents were given during the 1st and 3rd mo, and the
      "Centaur" suit was worn on the last day of bed rest and during the day time for
      several days after bed rest. Diet supplements were taken during the 1st and 4th
      mo of HDBR. Tilt tests were run before and after HDBR. RESULTS: After the HDBR,
      none of the CM subjects, had pre-syncopal or syncopal symptoms during tilt tests:
      BP was well maintained in the CM group, while heart rate and BP changed in the No
      CM group. In plasma, atrial natriuretic peptide (ANP) increased in both groups
      and remained high throughout HDBR, while aldosterone increased and remained
      elevated in the No-CM group. Natriuresis was decreased during HDBR. CONCLUSION:
      The CM protocols used during this study were efficient and prevented orthostatic
      intolerance for the four CM subjects. It would be necessary to obtain more data
      regarding this set of CM protocols on female subjects to lead to statistical and
      formal conclusions.

PMID- 10902935
TI  - The influence of gender and menstrual phase on thermosensitivity during cold
      water immersion.
AB  - BACKGROUND: This investigation evaluated the influence of gender and phase of
      menstrual cycle [follicular (FOL: days 2-6) and luteal (LUT: days 19-24) phases]
      on thermosensitivity and metabolic heat production (HP) during cold water
      immersion (20 degrees C) in 10 females (22.4 +/- 2.8 yr) and 16 males (22.4 +/-
      2.9 yr). METHODS: Following a 20-min baseline period (BASE), subjects were
      immersed until esophageal temperature (Tes) reached 36.5 degrees C or for a
      maximum pre-occlusion (Pre-OCC) time of 40 min. An arm and thigh cuff were then
      inflated to 180 and 220 mmHg, respectively, for 10 min (OCC). Following release
      of the inflated cuffs (Post-OCC), the slope (beta) of the relationship between
      the decrease in Tes and the increase in HP was used to quantify
      thermosensitivity. RESULTS: ANOVA revealed no significant difference in
      thermosensitivity between phases of the menstrual cycle or between men and women
      (FOL = -2.76, LUT = -3.05, Males = -3.24 W x kg(-1) x degrees C(-1)). A
      significant (p < 0.05) main effect for gender for HP, and a significant (p <
      0.05) main effect for menstrual phase for mean skin temperature (Tsk) were
      observed. CONCLUSIONS: These data suggest, despite gender differences in HP, that
      the thermosensitivity of HP during cold water immersion is similar between males
      and females and is not influenced by menstrual cycle phase. Therefore, these data
      indicate that when faced with a cold challenge, women respond similarly to men in
      both phases of their menstrual cycle.

PMID- 10902936
TI  - Effects of heterogeneous structure and diffusion permeability of body tissues on
      decompression gas bubble dynamics.
AB  - To gain insight into the special nature of gas bubbles that may form in
      astronauts, aviators and divers, we developed a mathematical model which
      describes the following: 1) the dynamics of extravascular bubbles formed in
      intercellular cavities of a hypothetical tissue undergoing decompression; and 2)
      the dynamics of nitrogen tension in a thin layer of intercellular fluid and in a
      thick layer of cells surrounding the bubbles. This model is based on the
      assumption that, due to limited cellular membrane permeability for gas, a value
      of effective nitrogen diffusivity in the massive layer of cells in the radial
      direction is essentially lower compared to conventionally accepted values of
      nitrogen diffusivity in water and body tissues. Due to rather high nitrogen
      diffusivity in intercellular fluid, a bubble formed just at completion of fast
      one-stage reduction of ambient pressure almost instantly grows to the size
      determined by the initial volume of the intercellular cavity, surface tension of
      the fluid, the initial nitrogen tension in the tissue, and the level of final
      pressure. The rate of further bubble growth and maximum bubble size depend on
      comparatively low effective nitrogen diffusivity in the cell layer, the tissue
      perfusion rate, the initial nitrogen tension in the tissue, and the final ambient
      pressure. The tissue deformation pressure performs its conservative action on
      bubble dynamics only in a limited volume of tissue (at a high density of formed
      bubbles). Our model is completely consistent with the available data concerning
      the random latency times to the onset of decompression sickness (DCS) symptoms
      associated with hypobaric decompressions simulating extravehicular activity. We
      believe that this model could be used as a theoretical basis for development of
      more adequate methods for the DCS risk prediction.

PMID- 10902937
TI  - Cold stress, near drowning and accidental hypothermia: a review.
AB  - This paper reviews literature on the topic of cold stress, near-drowning and
      hypothermia, written mainly since the last review of this type in this journal.
      The main effects of cold stress, especially in cold water immersion, include the
      "cold shock" response, local cooling causing decrements in physical and mental
      performance, and ultimately core cooling as hypothermia occurs. The section on
      cold-water submersion (near-drowning) includes discussion regarding the various
      mechanisms for brain and body cooling during submersion. The mechanisms for cold
      induced protection of the anoxic brain are discussed with attention given to
      decreased brain temperature and the Q10 principle, the mammalian dive reflex and
      a newly considered mechanism; cold-induced changes in neurotransmitter release
      (i.e., glutamate and dopamine). The section on the post-cooling period includes
      the post-rescue collapse and subsequent rewarming strategies used in the field,
      during emergency transport or in medical facilities. Recent research on topics
      such as inhalation warming, body-to-body warming, radio wave therapy, warm water
      immersion, exercise, body cavity lavage, and cardiopulmonary bypass is reviewed.
      Information on new methods of warming, including arteriovenous anastomoses (AVA)
      warming (by application of heat- with or without negative pressure application-to
      distal extremities in an effort to increase AVA blood flow), forced-air warming,
      and peripheral vascular extracorporeal warming, are discussed.

PMID- 10902938
TI  - Thermal and metabolic responses of women.

PMID- 10902940
TI  - 2000 award winners of the Aerospace Medical Association.

PMID- 10902941
TI  - Signal processing using Wavelet transforms.

PMID- 10902939
TI  - In-flight birth: an exhilarating initial C-141 training mission.

PMID- 10902942
TI  - Advances in clinical psychology: introduction to the second millennial issue.

PMID- 10902943
TI  - Dimensions of the counseling process. 1948.

PMID- 10902944
TI  - Ironies in the history of psychotherapy research: Rogers, Bordin, and the shape
      of things that came.
AB  - This paper discusses Bordin's (1948) contribution to this journal in the context
      of the historical period in which it was written, in relation to Bordin's later
      contributions to the field of psychotherapy research, and in anticipation of
      issues that seem likely to emerge as critical in that field during the coming
      decades.

PMID- 10902945
TI  - Some considerations relative to nondirective counseling as therapy. 1948.

PMID- 10902946
TI  - Client-centered therapy: where has it been and where is it going? A comment on
      Hathaway (1948)
AB  - We review the article by Hathaway (1948) critiquing nondirective therapy. We
      summarize Hathaway's concerns about nondirective therapy and psychotherapy
      research in general and consider the historical context of the article. Then we
      discuss progress on methodological concerns raised by Hathaway, empirical
      evidence obtained in the last 50 years about the efficacy of client-centered
      therapy and other kinds of psychotherapy, the current status of client-centered
      therapy, and projections for the future.

PMID- 10902947
TI  - The principles and methods of objective psychotherapy. 1949.

PMID- 10902948
TI  - A current reader's response to the article of 50 years ago by Karpman, B. (1949):
      "The principles and methods of objective psychotherapy".
AB  - The first aim is to describe the psychotherapy of 1949 in the light of today's
      psychotherapies. The old psychotherapy is suited to treating severely ill
      patients. It does not use free association, but rather is focused on current
      problems. It uses dreams, yet it also uses homework and bibliotherapy. The second
      aim is to critique the treatment. Consistent with its era. it does not make use
      of medications, and there is an absence of references to psychotherapy research,
      which was then just starting. The treatment relies over-heavily on the authority
      of the therapist. A third aim is to describe the changes in our field in the past
      50 years and examine the predictions for the future. Although the treatment is
      called objective psychotherapy, it does not make use of the most up-to-date means
      of measuring accuracy of interpretations, such as the Core Conflictual
      Relationship Theme (CCRT) method and other methods like it.

PMID- 10902949
TI  - A critique of the theoretical contributions of nondirective therapy. 1948.

PMID- 10902950
TI  - Cognitive therapy: looking backward, looking forward.
AB  - This article reviews some of the historical factors associated with the
      unprecedented strength and popularity of cognitive therapy, and offers
      predictions for the next half-century of this approach to treatment. It is
      predicted that the future will bring with it increased demands on cognitive
      therapy for evaluation of processes of change (including identification of
      therapeutic specifics and nonspecifics, technical specification of the process of
      therapy, and examination of therapist and patient predictors of change), and
      accountability and efficiency in the public and private sectors. With the
      increase in personal autonomy, globalization, and technology, the demands from
      the general public also will increase. One possible risk of the trend towards
      increased technology is that cognitive therapy may become overly technical.
      Although specific therapy techniques are crucial to delivering effective
      treatment, it is also the "nonspecifics" of therapy that add to the "art" of
      psychotherapy. The final challenge of cognitive therapy also may be the most
      difficult--to continue to be an empirically based science while maintaining its
      role in the art of healing.

PMID- 10902951
TI  - Nomenclature of psychiatric disorders and reactions. Office of the Surgeon
      General, Army Service Forces. War Department Technical Bulletin, Medical 203.
      1946.

PMID- 10902952
TI  - Fifty years of psychiatric nomenclature: reflections on the 1943 War Department
      Technical Bulletin, Medical 203.
AB  - War Department Technical Bulletin, Medical 203 is presented in historical context
      as the first psychodynamic nomenclature. The history of Medical 203 is presented
      to show how Medical 203 was adapted to become DSM-I. Medical 203 then is compared
      and contrasted to DSM-IV to illustrate how changes in the modern DSMs have led to
      an 800% increase in the number of psychiatric diagnoses over the last half
      century. The role of critical history is emphasized in evaluating those changes
      and in speculating about the next 50 years of psychiatric nomenclature.

PMID- 10902953
TI  - The test performance of the brain injured. 1947.

PMID- 10902955
TI  - Women, careers, and academic radiology.

PMID- 10902954
TI  - Commentary and perspectives on R.M. Allen's "The test performance of the brain
      injured".
AB  - Significant advances have occurred in the study of the neuropsychology of head
      injury since R.M. Allen's (1947) paper. These include better conceptualization of
      brain-behavior relationships, advances in neuropsychological instruments,
      normative data and assessment paradigms, structural and functional brain imaging
      techniques, greater understanding of the mechanisms of brain injury, and the
      classification and quantification of brain injury. However, because of conceptual
      and methodological problems there has been a relative lack of progress in
      understanding the etiology of symptoms in mild head injury. To date, studies of
      mild head injury have produced widely mixed findings. Further, orthopedic injury,
      chronic pain, litigation, and other conditions may also produce cognitive and
      behavioral changes similar to those seen in mild head injury. The authors outline
      a study design with two control groups (other injury and noninjury) contrasted
      with mild closed head injury to resolve the issue of whether functional changes
      following an injury are due to a specific head injury effect or to more general
      injury factor(s). Results of extant studies using this design are discussed,
      along with future directions for neuropsychological assessment.

PMID- 10902956
TI  - Ghost imaging for targeting breast masses with MR imaging: a phantom study.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to test the accuracy of
      ghost magnetic resonance (MR) imaging for guiding core biopsies of simulated
      breast masses in a tissue phantom. MATERIALS AND METHODS: A tissue MR phantom
      implanted with 20 grapes as targets was placed into an interventional breast MR
      coil. The locations of the centers of the targets were determined, recorded, and
      saved as ghost images. A nonmagnetic phantom needle was constructed to avoid
      imprecision secondary to magnetic field inhomogeneity and was used to determine
      the three-dimensional location of the needle tip in the center of each grape on
      the ghost image. Once the positions were determined, the true needle was placed
      and biopsy specimens were taken. The needle was inspected for the presence of
      pulp after each pass. Each grape was inspected to determine the location of the
      needle track in relation to the center of the grape. The duration of the
      procedure was recorded. RESULTS: All grapes were hit by the biopsy needle, as
      demonstrated either by pulp within the needle or by a needle track within the
      grape. Seventeen of the 20 grapes (85%) were hit centrally. Three were sampled
      eccentrically, up to 5-6 mm from the center. Each biopsy took approximately 1
      hour. CONCLUSION: These results suggest that ghost imaging may be ideal for
      needle guidance in core biopsy or preoperative localization, as it extends the
      period of visibility after a bolus injection of contrast material. Additionally,
      using a phantom needle for localization appears to overcome imprecision due to
      magnetic field inhomogeneity of the needle.

PMID- 10902957
TI  - Career advancement of men and women in academic radiology: is the playing field
      level?
AB  - RATIONALE AND OBJECTIVES: The authors' purposes were to determine if there are
      gender differences in the speed of promotion and/or academic productivity in
      academic radiology and if this situation had changed since a previous study was
      performed in 1987. MATERIALS AND METHODS: Surveys were distributed to faculty
      members of academic radiology departments in May 1997. A total of 707 surveys
      were analyzed according to gender for time at rank for assistant and associate
      professor levels, in relation to publication rate, grant funding rate, and
      distribution of professional time. RESULTS: There was no difference between
      genders in the time at assistant professor rank. Among all current professors,
      women had been associate professors longer than men, but there was no difference
      between genders for those who had been in academic radiology for less than 15
      years. There was no gender difference at any rank in the rate of publishing
      original articles. There was no difference in funding rates, although men had
      more total grant support. Male associate professors reported spending more time
      in administration and slightly more time in total hours at work than did their
      female colleagues, and male professors spent slightly more time teaching
      residents. Otherwise, there is no difference in how men and women at any rank
      spend their professional time. There are, however, lower percentages of women in
      tenured positions and in the uppermost levels of departmental administration.
      CONCLUSION: The time at rank for men and women and their rate of publication
      appear to have equalized. Women still are underrepresented at the uppermost
      levels of departmental administration, however, and are less likely than men to
      hold tenured positions.

PMID- 10902958
TI  - Volume assessment of the normal female cervix with MR imaging: comparison of the
      segmentation technique and two geometric formula.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine the volume
      of the normal female cervix and to determine the geometric formula that yields
      the best estimate. MATERIALS AND METHODS: Magnetic resonance images of the pelvis
      in 30 young women were reviewed retrospectively. The volume of the cervix was
      estimated by using the formulas for an ellipse and a cylinder. Manual labeling
      and segmentation of the cervix were also performed, and the volume was calculated
      on the basis of the number and size of the voxels. Comparison of these methods
      was then performed by using a two-tailed Student t test. RESULTS: No
      statistically significant difference was found (P = .7) between the volume
      calculated with the segmentation technique (25.3 mL) and that estimated with the
      formula for a cylinder (24.8 mL). A statistically significant difference (P <
      .05) was found between the volume calculated with the segmentation technique and
      that estimated with the formula for an ellipse (16.4 mL). CONCLUSION: The normal
      volume of the cervix in this population of young women was approximately 25 mL.
      The volume of the cervix should be estimated with the formula for a cylinder.

PMID- 10902959
TI  - Distortion reduction for fast soft straightening of the colon.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to suppress the geometric
      distortion associated with soft straightening of the colon by moderately
      adjusting curved cross sections, which is equivalent to appropriately modifying
      the underlying electrical field. MATERIALS AND METHODS: A computational mechanism
      to reduce the geometric distortion associated with soft straightening was
      developed. Because the cause of distortion is uneven sampling of the colon wall
      with curved cross sections, the curved cross sections formed according to a
      numerically simulated electrical field were redistributed in the distortion
      reduction process. This mechanism can be directly incorporated into a previously
      published fast soft-straightening algorithm. Simulations were performed to
      evaluate the effectiveness of the mechanism, and a phantom colon with digitally
      implanted, spherical polyps was straightened and rendered to visually display the
      efficacy of the mechanism. RESULTS: The distortion reduction mechanism was
      advantageous regarding shape preservation of polyps and alleviated distortion
      substantially. The mechanism occupied only a small portion of the total
      processing time. CONCLUSION: The distortion reduction mechanism can effectively
      reduce the geometric distortion associated with soft straightening at little
      computational cost and has potential for use with computed tomographic
      colonography.

PMID- 10902960
TI  - Data analysis for detection and localization of multiple abnormalities with
      application to mammography.
AB  - RATIONALE AND OBJECTIVES: In assessing diagnostic accuracy it is often essential
      to determine the reader's ability both to detect and to correctly locate multiple
      abnormalities per patient. The authors developed a new approach for the detection
      and localization of multiple abnormalities and compared it with other approaches.
      MATERIALS AND METHODS: The new approach involves partitioning the image into
      multiple regions of interest (ROIs). The reader assigns a confidence score to
      each ROI. Statistical methods for clustered data are used to assess and compare
      reader accuracy. The authors applied this new method to a reader-performance
      study of conventional film images and digitized images used to detect and locate
      malignant breast cancer lesions. RESULTS: The ROI-based approach, the free
      response receiver operating characteristic (FROC) curve, and the patient-based
      approach handle the estimation of the false-positive rate (FPR) quite
      differently. These differences affect the measures of the respective areas under
      the curves. In the ROI-based approach the denominator is the number of ROIs
      without a malignant lesion. In the FROC approach the average number of false
      positive findings per patient is plotted on the x axis of the curve. In contrast,
      the patient-based approach mishandles the FPR by ignoring multiple detection
      and/or localization errors in the same patient. The FROC approach does not lend
      itself easily to statistical evaluations. CONCLUSION: The ROI-based approach
      appropriately captures both the detection and localization tasks. The
      interpretation of the ROI-based accuracy measures is simple and clinically
      relevant. There are statistical methods for estimating and comparing ROI-based
      estimates of accuracy.

PMID- 10902961
TI  - Percutaneous nephrostomy in infants and children.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to review the authors'
      experience with percutaneous nephrostomy during an 11-year period, paying special
      attention to indications and outcomes. MATERIAL AND METHODS: The records of 71
      percutaneous nephrostomy procedures performed on 59 children at the authors'
      institution from January 1987 through December 1997 were retrospectively
      reviewed. In these children, ultrasonography was used for puncture and
      fluoroscopy for catheter insertion. Local anesthesia with sedation was used and
      later replaced by general anesthesia. Loop-end catheters were employed. The
      smallest patient weighed 1,200 g, and the mean patient age was 3.4 years.
      RESULTS: The mean duration of drainage was 60 days, and the longest time was 11
      months. Indications were mainly obstructions, with congenital obstruction (n =
      28) and postoperative obstruction (n = 26) being the most common. Obstructive
      pyelitis, malignancy, stone, renal cystic disease, trauma, and neurogenic bladder
      disturbance were also indications. No complications such as loss of the kidney,
      serious infection, or hemorrhage of clinical importance were observed.
      Obstruction was successfully relieved in all patients, but 12 kidneys and five
      hemikidneys did not recover function and were eventually removed. CONCLUSION: The
      percutaneous nephrostomy procedure is a safe technique that can be used
      successfully for short- and longterm drainage in all children, even in small
      infants and those with solitary kidneys, and is a valuable adjunct to surgery.

PMID- 10902962
TI  - Automated registration of frontal and lateral radionuclide lung scans with
      digital chest radiographs.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to develop and evaluate a
      fully automated method that spatially registers anterior, posterior, and lateral
      ventilation/perfusion (V/Q) images with posteroanterior and lateral digital chest
      radiographs to retrospectively combine the physiologic information contained in
      the V/Q scans with the anatomic detail in the chest radiographs. MATERIALS AND
      METHODS: Gray-level thresholding techniques were used to segment the aerated lung
      regions in the radiographic images. A variable-thresholding technique combined
      with an analysis of image noise was used to segment the adequately perfused or
      ventilated lung regions in the scintigraphic images. The physical dimensions of
      the segmented lung regions in images from both modalities were used to properly
      scale the radiographic images relative to the radionuclide images. Computer
      determined locations of anatomic landmarks were then used to rotate and translate
      the images to achieve registration. Pairs of corresponding radionuclide and
      radiographic images were enhanced with color and then merged to create
      superimposed images. RESULTS: Five observers used a five-point rating scale to
      subjectively evaluate four image combinations for each of 50 cases. Of these
      ratings, 95.5% reflected very good, good, or fair registration. CONCLUSION: The
      automated method for the registration of radionuclide lung scans with digital
      chest radiographs to produce images that combine functional and structural
      information should benefit nuclear medicine physicians and radiologists, who must
      visually correlate images that differ greatly in physical size, resolution
      properties, and information content.

PMID- 10902963
TI  - Development and assessment of a radiology core curriculum in health care policy
      and practice.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the
      feasibility of implementing a core curriculum in health policy and practice for
      radiology residents and fellows, to determine whether such a curriculum would be
      considered professionally valuable by participants, and to determine if the
      curriculum would influence participants' careers. MATERIALS AND METHODS: A core
      curriculum in health policy and practice was developed, involving 19 seminars
      presented over 5 weeks. Twelve faculty members presented comprehensive and
      integrated information relevant to current and future radiology practice. Topic
      clusters included health care structure and payment, technology and health
      services, radiology practice management, and career issues. Classroom teaching
      was supplemented by a course syllabus and resource library. Participants were
      surveyed following each seminar and at the conclusion of the curriculum. RESULTS:
      Participants described their baseline knowledge of each topic as weak. As a
      result of the curriculum, self-described knowledge ratings increased
      considerably. Interest in curriculum topics and perception of their importance
      and relevance to radiology practice increased. Of respondents, 84% (26 of 31)
      described the curriculum as having very good or excellent educational value. All
      respondents indicated that the curriculum should be repeated in the future, 42%
      (13 of 31) indicated that the curriculum motivated them to pursue further related
      education, and 61% (19 of 31) developed interest in personal involvement in
      administrative issues and radiology organizations. CONCLUSION: A core curriculum
      in health policy and practice was successfully integrated into radiology
      training. The curriculum resulted in increased knowledge, interest, and perceived
      importance of medical management issues by residents and fellows and stimulated
      their interest in pursuing further management education and involvement in
      radiology administration and organizations.

PMID- 10902964
TI  - Data analysis for detection and localization of multiple abnormalities with
      application to mammography.

PMID- 10902965
TI  - World Wide Web resources for radiology residents.

PMID- 10902966
TI  - US in the emergency department.

PMID- 10902967
TI  - What difference would a National Institute of Biomedical Imaging and
      Bioengineering make?

PMID- 10902968
TI  - The role of hepatic peroxisome proliferator-activated receptors (PPARs) in health
      and disease.
AB  - The liver has long been known to respond to exposure to certain chemicals with
      hyperplasia and proliferation of the peroxisomal compartment. This response is
      now known to be mediated by specific receptors. The peroxisome proliferator
      activated receptors (PPARs) were cloned 10 years ago, and in that interval, have
      been found to serve as receptors for a number of endogenous lipid compounds, in
      addition to the peroxisome proliferators that originally led to their study.
      Three receptors, designated the alpha, delta, and gamma receptors, have been
      found in mammals. PPARalpha: is the most abundant form found in the liver, with
      smaller amounts of the delta and gamma forms also expressed there. Kupffer cells,
      like other macrophages, appear to express the alpha and gamma isoforms. Hepatic
      stellate cells are reported to express the gamma isoform. PPARalpha knock-out
      mice fail to undergo peroxisome proliferation when challenged with the
      proliferators. Moreover, they have severe derangements of lipid metabolism,
      particularly during fasting, indicating that normal function of the alpha
      receptors is needed for lipid homeostasis. This in turn suggests that inadequate
      PPAR-mediated responses may contribute to abnormal fatty acid metabolism in
      alcoholic and non-alcoholic steatohepatitis. Recent information suggests that
      PPARgamma receptors may be important in control of the activation state of the
      stellate cells, and their repression or inactivation may predispose to hepatic
      fibrosis. The first approved drug that specifically activates PPARgamma,
      troglitazone, has rarely been found to cause serious liver injury. Although this
      is likely to represent an idiosyncratic reaction, the medical community will need
      to be alert to the possibility that activation or blockade of these receptors may
      cause hepatic dysfunction.

PMID- 10902969
TI  - Red blood cells attenuate sinusoidal endothelial cell injury by scavenging
      xanthine oxidase-dependent hydrogen peroxide in hyperoxic perfused rat liver.
AB  - AIMS/BACKGROUND: Rat liver perfused with an oxygenated buffered solution alone
      results in degenerative changes even when the perfusion flow is accelerated to
      give a sufficient oxygen supply. On the other hand, perfusion media supplemented
      with red blood cells (RBCs) preserve the viability of the liver. The present
      study was conducted to clarify how RBCs protect the isolated perfused liver.
      METHODS: The liver was perfused with and without RBCs in a perfusate equilibrated
      with supra-physiological oxygen tension at regulated inflow pressures, and
      controlled hepatic oxygen consumption. We examined alanine aminotransferase and
      purine nucleoside phosphorylase activity in the perfusate as specific markers of
      liver cells injury. Hydrogen peroxide (H2O2) production and morphological changes
      were determined using cerium electron microscopy. Apoptosis was detected by
      measuring CPP 32 protease activity and using TdT-mediated dUTP-digoxigenin nick
      end-labeling. RESULTS: When the liver was perfused with RBC-free buffer, H2O2
      production and consequent injury progressing to apoptosis were initiated in the
      sinusoidal endothelial cells (SECs). After SECs were injured, H2O2 appeared in
      the hepatocytes. H2O2 production and associated degenerative changes were
      attenuated both morphologically and enzymatically by the addition of RBCs, a
      specific xanthine oxidase (XOD) inhibitor and the H2O2 radical scavenger,
      catalase. CONCLUSIONS: In the liver perfused with RBC-free buffer, H2O2
      production and consequent injury were initiated in SECs. RBCs attenuate liver
      injury by scavenging XOD-dependent H2O2.

PMID- 10902970
TI  - Protein expression of MDM2 and its clinicopathological relationships in human
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The transcription of mdm2 gene is activated by p53 and this
      limits the growth-suppressing activity of p53 by direct binding. It has been
      reported that MDM2 protein is overexpressed in several types of cancers. However,
      there have been no immunohistochemical studies on MDM2 in human hepatocellular
      carcinoma (HCC). METHODS: We immunohistochemically examined the expression of
      MDM2 and the relationships between its expression and histological grade,
      clinicopathological parameters, p53 expression and patient survival in 107
      patients with HCC. RESULTS: The frequency of MDM2 positivity in the nuclei of HCC
      cells was 28/107 (26%). There was no correlation between the MDM2 expression and
      HCC grade. However, positivity of MDM2 expression significantly correlated with
      small HCC size (p<0.05, chi2 test) and the absence of vascular invasion (p<0.01,
      chi2 test). No significant differences were noted between MDM2 expression and
      capsular invasion or satellite nodules. Expression of MDM2 showed a significantly
      positive correlation with expression of p53 (p<0.03, chi2 test). Patients with
      positive expression of MDM2 had poorer prognosis than patients with negative MDM2
      expression. MDM2 expression was the most useful independent factor for overall
      survival (p=0.0001). CONCLUSIONS: MDM2 was expressed in 26% of HCC, and its
      expression correlated positively with p53 mutations. MDM2 over-expression is a
      useful predictor of poor prognosis in patients with HCC following hepatic
      resection.

PMID- 10902971
TI  - Increased midkine expression in intrahepatic cholangiocarcinoma:
      immunohistochemical and in situ hybridization analyses.
AB  - AIMS/BACKGROUND: Midkine (MK) is a novel heparin-binding growth factor whose gene
      was identified in embryonal carcinoma cells in the early stages of retinoic acid
      induced differentiation. This study investigates the overexpression of MK in
      intrahepatic cholangiocarcinoma (CC). METHODS: Forty-five primary CC specimens
      from patients (aged 19-81 years, 24 males and 21 females) were examined.
      Histologically, 17 cases of CC were classified as the well-differentiated type,
      19 as moderately-differentiated and 9 as poorly-differentiated.
      Immunohistochemical analysis was performed using a rat IgG2a monoclonal antibody
      against the carboxyl terminal region of human MK. RESULTS: We successfully
      applied this monoclonal antibody against MK to analyze archival paraffin
      sections. The cancer tissues showed a positive reaction to this antibody, and
      there was an intense reaction in their cytoplasm. Approximately 40% of
      individuals with CC (17/45) had tumor cells that expressed MK, and these were
      classified into the following types: moderately-differentiated type (9/19), well
      differentiated type (8/17) and poorly-differentiated type (0/ 9). In situ
      hybridization analysis revealed that signals of MK transcripts were found in the
      cytoplasm of the cancer cells; the distribution and localization of the MK
      transcript signals determined by in situ hybridization analysis were similar to
      those obtained by immunohistochemical analysis. CONCLUSIONS: These findings
      revealed that CC express increased MK at the messenger RNA and protein levels.

PMID- 10902972
TI  - GB virus-C/hepatitis G virus infection in a hepatitis C virus endemic village:
      prevalence in residents with low educational attainment and frequent recovery in
      females.
AB  - AIMS/BACKGROUND: GB virus-C/hepatitis G virus (HGV) is a newly identified
      flavivirus, which may share the same mode of transmission as hepatitis C virus
      (HCV). The aim of this study was to investigate associated factors of HGV
      infection and clearance in a HCV endemic village in southern Taiwan. METHODS:
      Five hundred and ninety-four residents of a village in southern Taiwan were
      enrolled for hepatitis virus screening. Clinical features were recorded and a
      questionnaire addressing the possible routes of transmission was filled in by the
      participating residents. RESULTS: The prevalence of antibody to hepatitis C virus
      and hepatitis B surface antigen in the 594 residents was 70.7% and 19.5%
      respectively. Of the 399 residents tested for HGV RNA, GB virus-C/Hepatitis G
      virus envelop 2 protein (HGV-E2) antibody, and HCV RNA, the prevalence was 13.5%,
      25.3%, 53.1% respectively. Multivariate logistic regression analysis showed that
      low educational attainment was associated with HGV infection, old age and low
      educational attainment were associated with HCV infection, and female gender was
      associated with HGV clearance. Alanine aminotransferase (ALT) values were
      significantly higher for residents with HCV infection alone, HBV infection alone,
      and co-infection of HCV and HBV than for those without HBV, HCV, and HGV
      infection. There were no differences in ALT values between subjects with HGV
      infection alone and those without HBV, HCV, and HGV infections. Residents with co
      infection of HGV and HBV, or HGV and HCV had ALT values similar to those with HBV
      or HCV infection alone. CONCLUSION: HGV infection is common in the HCV endemic
      village. The transmission of HGV is closely related to low educational
      attainment. HGV clearance is frequently encountered in females. Co-infection of
      HGV does not compound hepatocellular inflammation.

PMID- 10902973
TI  - Androgen dependency of hepatocarcinogenesis in TGFalpha transgenic mice.
AB  - AIMS/BACKGROUND: Sex difference has been shown to play a major role in
      susceptibility to the development of hepatocellular carcinoma in humans and
      rodents. In order to clarify the necessity of androgens in hepatic tumorigenesis
      in transgenic mice overexpressing transforming growth factor (TGF) alpha (MT42),
      androgen supplement after castration and the LH-RH analogue, leuprolerin acetate,
      were tested in an experimental model in MT42. METHODS: Male MT42 mice were
      castrated and supplemented with dihydrotestosterone (DHT) every three months up
      to 15 months and hepatic tumorigenesis was observed. Leuprolerin acetate was
      administered to both male and female MT42 mice once a month from 2 months after
      birth to 15 months to observe the effect on hepatic tumorigenesis. Northern
      hybridization was performed to detect messenger RNA (mRNA) of TGFalpha expression
      and the rate of proliferative cell nuclear antigen (PCNA) staining compared with
      the castrated and non-treated mice. RESULTS: Castration tended to decrease both
      body and liver weight in MT42 mice which was then restored by DHT. Untreated MT42
      males developed 11 liver tumors in 6 mice. Hormonal treatment including
      castration and DHT supplementation did not change the expression of TGFalpha
      mRNA. Castrated transgenic mice developed 2 liver tumors in 2 out of 6 mice and
      DHT supplementation after castration restored the number of liver tumors to 9 in
      5 of 6 mice. PCNA labelling indexes of liver tumors and adjacent non-tumorous
      liver were 7.1% (p<0.05): 0.6% in untreated MT42, 3.2%: 0.2% in castrated MT42
      and 10.1% (p<0.05): 0.5% in MT42 with castration and DHT supplementation
      (significant difference compared with castrated mice). Leuprolerin acetate
      treated MT42 males developed one liver tumor in 6 mice compared to MT42
      administered with saline as a vehicle control in which group 7 liver tumors in 6
      male MT42 were observed. Tumors in castrated-MT42 and leuprolerin treated-MT42
      were smaller than those in control MT42 mice. CONCLUSION: TGFalpha related
      hepatocarcinogenesis and hepatocyte proliferation are increased by androgenic
      stimulation. Suppression of androgens may be useful for the treatment of TGFalpha
      related liver tumors.

PMID- 10902974
TI  - HLA class II genotypes associated with chronic hepatitis C virus infection and
      response to alpha-interferon treatment in Poland.
AB  - AIMS/BACKGROUND: Recent evidence suggests that spontaneous clearance of hepatitis
      C virus (HCV) may be associated with the HLA DQB1*0301 allele but there is still
      some debate over the role of other alleles and HLA haplotypes in HCV infection.
      As this may best be resolved by studying genetically different populations, we
      have investigated HLA class II-encoded susceptibility and resistance to HCV
      infection in a relatively sedentary population of patients from northwestern
      Poland. METHODS: The distributions of HLA class II DRB1, DQA1, DQB1 and DPB1
      alleles were determined by standard PCR-protocol in 129 unrelated patients with
      chronic hepatitis C (anti-HCV and HCV-RNA positive) and 103 healthy unrelated
      racially-matched control subjects. Fifty-five patients were treated with alpha
      interferon (5 MIU thrice weekly for 6 months) out of whom 29 showed a complete
      response and 26 were non-responders. RESULTS: A significantly reduced frequency
      of the DQB1*0301 allele in the patients was observed (24.0% vs. 38.8%; p=0.015).
      Additionally, two different DR-DQ haplotypes were found to be associated with
      chronic HCV infection: DRB1*1501-DQA1*01-DQB1*0602 (24.0% vs. 12.6%; p= 0.027)
      and DRB1*0701-DQA1*0201-DQB1*02 (31.8 vs. 12.6%; p=0.0006), the latter difference
      being most pronounced in those patients who responded to alpha-interferon
      treatment (41.4% vs. 12.6%; p=0.00048). CONCLUSIONS: The results confirm the
      negative association between chronic HCV and DQB1*0301 and identify two novel
      genetic associations. In particular, the DRB1*0701-DQA1*0201-DQB1*02 haplotype is
      associated with both chronic infection and response to alpha-interferon.
      Interestingly, the same haplotype is reportedly associated with non-response to
      hepatitis B vaccination.

PMID- 10902975
TI  - A novel binding site for the native hepatic acute-phase protein alpha1
      antitrypsin expressed on the human hepatoma cell line HepG 2 and intestinal cell
      line Caco 2.
AB  - AIMS/BACKGROUND: alpha1-antitrypsin (alpha1-AT) is a hepatic acute phase protein
      which predominantly inhibits neutrophil elastase. Besides this major function, we
      have also previously shown that alpha1-AT markedly increased H-ferritin mRNA
      expression and ferritin synthesis in the human hepatoma cell line HepG 2. These
      actions suggest that alpha1-AT might interact with HepG 2 cells via a specific
      cell surface binding site. METHODS AND RESULTS: Using radio-labelled native
      alpha1-AT, we observed saturable binding to HepG 2 cells with a dissociation
      constant (Kd) of 63.3+/-6.9 nM and a maximal density of binding sites (Bmax) of
      0.34+/-0.05 pmol/10(6) cells equivalent to 195,800+/-29,200 sites/cell. The
      binding of [125I]alpha1-AT was time dependent with a calculated association rate
      constant of 9.22+/-1.84x10(4)xM(-1)xmin(-1). Binding was highly specific since
      other acute phase proteins or protease inhibitors failed to block binding.
      Although alpha1-AT-trypsin, alpha1-AT-elastase and the pentapeptide FVYLI, the
      minimal binding sequence for the SEC receptor, increased [125I]alpha1-AT binding,
      in long term experiments these complexes failed to influence the number of alpha1
      AT binding sites. Specific, saturable binding of [125I]alpha1-AT was also found
      on the human intestinal epithelial Caco 2 cells, but not on fibroblast or
      leukaemic cell lines. CONCLUSION: These experiments demonstrate a specific, high
      affinity binding site for native alpha1-AT on HepG 2 and Caco 2 cells, cell lines
      derived from tissues involved in the acute phase response.

PMID- 10902976
TI  - Poor association of TT virus viremia with hepatocellular carcinoma.
AB  - AIM: The aim of this study was to clarify the relationship between TT virus (TTV)
      infection and the development of hepatocellular carcinoma. METHODS: TTV from
      serum was examined in 224 patients with hepatocellular carcinoma (HCC) and 106
      patients with chronic liver disease (CLD) but without HCC who were admitted to
      our hospital between 1995-1997. As controls, 48 patients without liver disease
      were also examined. TTV DNA was detected using nested PCR method after extraction
      of DNA from serum. RESULTS: TTV DNA was detected in 29/224 (13%) of patients with
      HCC; in 14% (4/28) of HCC patients negative for both hepatitis B virus surface
      antigen (HBsAg) and anti-hepatitis C virus antibody (anti-HCV), in 9% (2/22) of
      HCC patients positive for HBsAg, and in 12% (21/170) of HCC patients positive for
      anti-HCV. The prevalence of TTV DNA in HCC patients (13%) was not significantly
      higher than in CLD patients (22%). There were no significant differences in age,
      gender, liver function, tumor biology (size, TNM classification), other viral
      markers, or amount of alcohol intake between TTV-positive and -negative HCC
      patients. Only a history of blood transfusion was significantly more frequent in
      TTV-positive HCC patients than in TTV-negative cases (p= 0.02). Coinfection with
      TTV did not correlate with the severity of HCV-positive liver disease. There was
      no significant difference in prognosis between TTV-positive and -negative HCC
      patients. CONCLUSIONS: TTV does not seem to contribute to the development of HCC
      from chronic liver disease and is not correlated with severity of liver disease.

PMID- 10902977
TI  - Do gastric and oesophageal varices bleed at different portal pressures and is
      TIPS an effective treatment?
AB  - BACKGROUND: It has been suggested that gastric varices bleed at lower
      portosystemic pressure gradients (PSPG) than oesophageal varices and that
      transjugular intrahepatic portosystemic shunt (TIPS) is a particularly effective
      treatment in these patients. AIMS: This study was undertaken to assess the
      difference in PSPG measured at the time of TIPS insertion between patients
      bleeding from gastric and those bleeding from oesophageal varices. Rebleeding and
      mortality rates between the two groups were also compared. PATIENTS AND METHODS:
      In a five year period, 64 patients (36 males and 28 females) undergoing TIPS for
      acute variceal bleeding had PSPG measured at the time of TIPS insertion. 12
      patients underwent TIPS for gastric variceal haemorrhage (GVH) and 52 for
      oesophageal variceal haemorrhage (OVH). The median age was 53 years and 40/64
      patients (63%) had alcoholic liver disease. The median Child's Pugh score was 8
      for GVH and 9 for OVH patients. Median follow up was 75 weeks. RESULTS: There was
      no significant difference in median PSPG between patients with GVH, 21 mmHg
      (range 15-30 mmHg) and OVH, 22 mmHg (range 12-45 mmHg). Following TIPS, PSPG was
      8.5 mmHg (range 3-11 mmHg) and 9 mmHg (range 4-20 mmHg) in GVH and OVH patients
      respectively. Rebleeding occurred in 2/12 (16%) GVH patients and 12/52 (23%) OVH
      patients (p= 1.0). Mortality during follow up was 25% (4/12) in the GVH and 25%
      (13/52) in the OVH patients. CONCLUSION: In this study, there was no difference
      between the pressures at which gastric and oesophageal varices bled. Rebleeding
      and mortality rates were similar in the two groups. TIPS is equally effective in
      the treatment of both oesophageal and gastric variceal haemorrhage.

PMID- 10902979
TI  - Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis.

PMID- 10902978
TI  - Absence of hepatitis C genome in semen of infected men by polymerase chain
      reaction, branched DNA and in situ hybridization.
AB  - BACKGROUND/AIMS: The presence or absence of hepatitis C virus (HCV) RNA in the
      semen of infected man remains controversial, mainly due to technical difficulties
      associated with nucleic acid detection. The aims of this study were to assess the
      presence of HCV RNA in spermatozoa and in seminal fluid using different
      polymerase chain reaction (PCR)- and non-PCR-dependent methods and, in the case
      of HCV presence, to correlate this detection with the viraemia. METHODS: Serum
      and semen from 25 chronically infected hepatitis C patients were studied. The
      semen was separated into spermatozoa and seminal fluid and HCV RNA was analysed
      in the two fractions using RT-PCR and branched DNA. The presence of HCV RNA in
      pelleted cells was also assessed using in situ hybridization. RESULTS: All three
      approaches failed to demonstrate HCV RNA in semen. The presence of an inhibitor
      of the PCR was demonstrated in seminal fluid but not in spermatoza. CONCLUSION:
      Our results confirmed the lack of detection of HCV RNA in semen by PCR- and non
      PCR-dependent techniques and support the view that viral contamination in semen
      remains, if present, at a very low level. Nevertheless, epidemiological studies
      are required to definitively assess the absence of sexual transmission of HCV

PMID- 10902980
TI  - Liver abscesses due to Fusobacterium species.

PMID- 10902981
TI  - A developmental view of the undernourished child: background and purpose of the
      study in Pangalengan, Indonesia.
AB  - OBJECTIVES: This is the first of a series of reports published in this supplement
      of an experimental study to test the validity of a conceptual model about the
      intellectual delay of undernourished children. This paper describes the model and
      outlines its empirical and theoretical basis. The model provides a conceptual
      framework for the multiple relationships among growth and developmental domains
      presumably affected by malnutrition. It allows for a statistical statement
      regarding the goodness of fit between data and theory. The model also identifies
      particular hypotheses regarding multiple distinct pathways of human development.
      The following questions were addressed: (1) what are the effects of early
      supplementary feeding on the physical growth, motor development and activity,
      mental development and behavior of infants and toddlers who are nutritionally at
      risk? (2) What are the effects of a micronutrient supplement in the presence and
      absence of a high-energy supplement? (3) What are the moderating effects of
      developmental level and timing of the intervention. DESIGN: The study was a
      randomized clinical trial involving two cohorts (12 and 18 months old) of
      nutritionally-at-risk children living in Pangalengan, West Java, Indonesia and
      three types of supplements: condensed milk + micronutrients; skimmed milk +
      micronutrients; and skimmed milk. The children were tested every 2 months for a
      period of 12 months.

PMID- 10902982
TI  - The eco-cultural context of the undernourished children in a study on the effects
      of early supplementary feeding in Indonesia.
AB  - OBJECTIVES: This paper describes the ecological and cultural backdrop of the
      subjects enrolled in an experimental study to test the validity of a conceptual
      model about the intellectual delay of undernourished children. DESIGN: The
      experiment was a 12-month clinical, randomized trial on the effects of early
      supplementary feeding on two cohorts of children classified as nutritionally-at
      risk. Three different supplements (condensed milk + micronutrients; skimmed milk
      + micronutrients; skimmed milk) were given to the children during 6 or 12 months
      of the study. SETTING: The plantations are 1500-1800 m above sea level in
      Pangalengan, 50 km south of Bandung, West Java. Temperature fluctuates from 10 to
      17 degrees C. A high yearly precipitation is approximately 3000 mm. Communities
      are laid out at 5-15 km from one another. Living conditions are modest. SUBJECTS:
      The 156 subjects were recruited from 24 day-care-centers (DCC) that serviced
      families of 24 communities in six tea plantations. The 12- and 18-month-old
      cohorts included 73 and 83 children, respectively; each cohort included three
      subgroups that received distinct supplements. OBSERVATIONS: The interactions of
      the caretakers with the children in the DCCs were consistent with the
      socialization for survival mode. A primary concern was the physical growth,
      health, cleanliness, sanitation and safety of the children. Stimulating children,
      providing toys and initiating play or other activities that would emphasize
      educational development had a low priority.

PMID- 10902983
TI  - Effects of an energy and micronutrient supplement on growth and development in
      undernourished children in Indonesia: methods.
AB  - OBJECTIVES: To describe the methodologies of a clinical trial on the effects of
      an energy and micronutrient supplement on the growth and development of
      undernourished children. DESIGN: This trial included two cohorts of children
      classified as nutritionally-at-risk who were randomly assigned to three
      treatments (condensed milk + micronutrients (E); skimmed milk + micronutrients
      (M); skimmed milk (S)). Supplements were given for a period up to 12 months.
      SETTING: Six tea plantations in Pangalengan, West Java were the site for this
      study. SUBJECTS: A 12-month-old (N=53) and an 18-month-old (N=83) cohort were
      recruited from 24 day-care-centers (DCC). Twenty children that received the S
      supplement were part of the 12- and 18 month-old cohort. Criteria for case
      inclusion were absence of chronic disease; length-for-age < or = -1 standard
      deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of
      the reference of the World Health Organization. VARIABLES: Social variables
      included assessment of health facilities, childcare, housing, income and parental
      education. Nutrition and growth variables included dietary intake measured over a
      24 hr period every 2 months; hemoglobin and three iron indicators measured at
      baseline, 6 and 12 months; anthropometry measured every 2 months and skeletal
      maturation measured every 6 months. Cognition and behavior included the
      assessment of mental and motor development and the behavior of the child under
      natural conditions. DATA ANALYSIS: An ANOVA was the statistic most frequently
      used to test inter-group differences and structural equation modeling was used to
      test the internal validity of the conceptual model of the study.

PMID- 10902984
TI  - A preliminary test of a developmental model for the study of undernourished
      children in Indonesia.
AB  - OBJECTIVES: Structural equation modeling of an abbreviated version of the
      conceptual model of the effects of micronutrient and energy supplementation on
      growth and development of undernourished children in West Java. The study focused
      on the baseline data from the Pangalengan longitudinal project. DESIGN: This
      trial included two cohorts of children classified as nutritionally-at-risk who
      were randomly assigned to three treatments (condensed milk + micronutrients (E);
      skimmed milk + micronutrients (M); skimmed milk (S)). Supplements were given for
      a period of up to 12 months. SETTING: The sites were six tea plantations in
      Pangalengan. SUBJECTS: A 12-month-old (n=53) and an 18-month-old (n=83) cohort
      were recruited from 24 day care centers. Twenty children that received the S
      supplement were part of the 12- and 18-month-old cohorts. Criteria for inclusion
      were: no chronic disease; length-for-age < -1 standard deviation (s.d.) and
      weight-for-length between -1 and -2 s.d. of the median of the reference of the
      World Health Organization. VARIABLES: Indicators of socioeconomic status were
      economic and educational resources; length-for-age and weight-for-length were
      used as indicators of nutritional status; motor development and motor activity
      were measured with custom-made procedures; and carrying by caretaker and
      manipulation of objects were used as indicators of caretaking and exploratory
      behavior. RESULTS: The model fitted the data of the older but not of the younger
      cohort (chi2 statistic and three other indices of goodness to fit). However,
      there were no differences between cohorts in the estimation of the models.

PMID- 10902985
TI  - Community-level determinants of child growth in an Indonesian tea plantation.
AB  - OBJECTIVES: The paper presents the results of an ecological-economic approach to
      identifying community-level factors that influence the physical growth of young
      children. DESIGN: A cross-sectional design was used to obtain both the
      anthropometry and the ecological-economic data. SETTING: The sites were 24
      communities located in a tea plantation near Bandung, West Java, Indonesia.
      SUBJECTS: 415 children between the ages of 6 and 18 months. METHODS:
      Epidemiological and ethnographic methods were used to measure community
      infrastructure and services related to child growth. Anthropometry was used to
      measure child growth. Econometric methods, including probit and ordinary least
      squares regression, were used to analyze the effect of community-level factors on
      child growth. RESULTS: Community vaccination programs, child care services,
      environmental sanitation and latrines were associated with better child growth.
      We concluded that community-level goods and services substantially contributed to
      health in early childhood.

PMID- 10902986
TI  - Nutritional intake of an undernourished infant population receiving an energy and
      micronutrient supplement in Indonesia.
AB  - OBJECTIVES: This paper reports the dietary intake (home, day care centers,
      supplement and breast milk) of the children in the clinical trial in Pangalengan.
      DESIGN: Two cohorts of children were randomly assigned to three treatments: E =
      1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ. Supplementation was
      given for 12 months. SETTING: The sites were six tea plantations in Pangalengan,
      West Java. SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort
      were recruited from day-care-centers. Twenty children who received S belong to
      the 12- and 18-month-old cohorts. Inclusion criteria were: no chronic disease;
      length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between 
      1 and -2 s.d. of the median of the reference of the World Health Organization.
      METHODS: E = 1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ.
      Supplementation was given for 12 months. Evaluations of intake were made at
      baseline and every 2 months thereafter. RESULTS: For the 12-month-old cohort the
      mean increase in daily energy intake approximately 2931 kJ for E, approximately
      1675 kJ for M, and approximately 837 kJ increase over the 6 months for the S
      group. For the 18-month-old cohort the changes were approximately 2512 kJ for E
      approximately 1675 for the M group and approximately 1047 for the S group.

PMID- 10902987
TI  - Effects of an energy and micronutrient supplement on anthropometry in
      undernourished children in Indonesia.
AB  - OBJECTIVES: This paper reports the effects of early supplementary feeding on body
      weight, length, head circumference and arm circumference among the children in
      the Pangalengan study. DESIGN: Two cohorts of children were randomly assigned to
      three treatments: E = 1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ.
      Supplementation was given for 12 months. SETTING: The sites were six tea
      plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (n = 53) and an
      18-month-old (n = 83) cohort were recruited from day-care centers. Twenty
      children that received S belonged to the 12- and 18-month cohorts. Inclusion
      criteria were: no chronic disease; length-for-age < or = -1 standard deviation
      (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the
      reference of the World Health Organization. METHODS: Length was measured with a
      portable measuring board; a Detecto scale with an accuracy of 0.1 kg was used for
      the measurement of body weight. Arm and head circumferences were measured using
      similar fiberglass tapes. RESULTS: Body weight showed effects on both cohorts at
      2, 8 and 12 months; head circumference showed effects at 4 months in the 12-month
      old cohort and at 10 months among the females of the 18-month-old cohort; and arm
      circumference showed effects across cohorts at 2, 8 and 12 months. In general the
      benefits are clearer for females and for the 12-month-old cohort.

PMID- 10902988
TI  - Effects of an energy and micronutrient supplement on motor development and motor
      activity in undernourished children in Indonesia.
AB  - OBJECTIVES: This paper reports the effects of an energy and micronutrient
      supplement on the motor development, motor milestones and motor activity of
      nutritionally at risk infants and toddlers in Pangalengan, Indonesia. DESIGN: Two
      cohorts of children were randomly assigned to three treatments E = 1171 kJ + 12
      mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ. Supplementation was given for 12
      months. SETTING: The sites were six tea plantations in Pangalengan, West Java.
      SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort were
      recruited from day-care-centers. Twenty children that received S belonged to the
      12- and 18-month-old cohorts. Inclusion criteria were: no chronic disease; length
      for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and 
      2 s.d. of the median of the reference of the World Health Organization. METHODS:
      Evaluations of intake were made at baseline and every 2 months thereafter. Motor
      development was assessed with the Bayley Scale and with a custom-made scale to
      assess gross motor development leading to bipedal locomotion. Motor activity was
      assessed through 4 h continuous observations of the child's interaction with the
      social and physical environment. RESULTS: In the 12-month-old cohort, as compared
      to the M and S groups the children that received the E supplement walked at an
      earlier age, had higher scores in the Bayley Scale and were motorically more
      active. Similar intergroup differences were observed in the 18-month-old cohort
      in the total motor activity score.

PMID- 10902989
TI  - Effects of an energy and micronutrient supplement on growth and activity,
      correcting for non-supplemental sources of energy input in undernourished
      children in Indonesia.
AB  - OBJECTIVES: This paper investigates simultaneously the growth and activity of
      children that received an early energy and micronutrient supplement, adjusting
      for all non-supplemental energy intakes. Any additional change in growth and
      activity after this adjustment was then compared across supplements at three
      points felt to be representative of the study. DESIGN: Two cohorts of children
      were randomly assigned to three treatments: E = 1171 kJ + 12 mg iron; M = 209 kJ
      + 12 mg iron; S = 104 kJ. Supplementation was given for 12 months. SETTING: The
      sites were six tea plantations in Pangalengan, West Java. SUBJECTS: A 12-month
      old (n = 53) and an 18-month-old (n = 83) cohort were recruited from day-care
      centers. Twenty children that received S belonged to the 12- and 18-month-old
      cohorts. Inclusion criteria were: no chronic disease; length-for-age < or = -1
      standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the
      median of the reference of the World Health Organization. METHODS: Length was
      measured with a portable measuring board; a Detecto scale with an accuracy of 0.1
      kg was used for the measurement of body weight. Arm and head circumferences were
      measured using similar fiberglass tapes. Motor activity was assessed through
      continuous 4 h observations at home and at day care centers. Anthropometry and
      activity were measured every two months over 12 months. RESULTS: After correcting
      for non-supplemental sources of energy intake, the effects of the supplement on
      weight and activity were observed at 2 months; effects on length and activity
      were observed at 6 months; and effects on weight alone were observed at 12
      months.

PMID- 10902990
TI  - Effects of an energy and micronutrient supplement on skeletal maturation in
      undernourished children in Indonesia.
AB  - OBJECTIVES: This paper reports the effects of an energy and micronutrient
      supplement on skeletal maturation of nutritionally at risk infants and toddlers
      in Pangalengan, Indonesia. DESIGN: Two cohorts of children were randomly assigned
      to three treatments: E = 1171 kJoule + 12 mg iron; M = 12 mg iron + 209 kJ; S =
      104 kJ. Supplementation was given for 12 months. SETTING: The sites were six tea
      plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (n = 53) and an
      18-month-old (n = 83) cohort were recruited from day-care-centers. Twenty
      children that received S belonged to the 12- and 18-month-old cohorts. Inclusion
      criteria were: no chronic disease; length-for-age < or = -1 standard deviation
      (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the
      reference of the World Health Organization. METHODS: Skeletal maturation was
      measured by X-ray of the left hand and wrist. The number of ossified centers and
      two different measures of skeletal age (Skel-1 and Skel-2) were the outcome
      variables measured. RESULTS: In the 12-month-old cohort, there were intergroup
      differences 6 and 12 months after baseline. First, the children in the E group
      were about 2 months more advanced in ossified centers than the children in the S
      group (P < 0.10). At 12 months, the children in the E group were about 3 months
      more advanced in skeletal age than the children in the M group. M group children
      were about 2.5 months behind the children in the S group.

PMID- 10902991
TI  - Effects of an energy and micronutrient supplement on mental development and
      behavior under natural conditions in undernourished children in Indonesia.
AB  - OBJECTIVES: This paper reports the effects of an energy and micronutrient
      supplement on mental development and on the social cognitive and emotionally
      regulatory behaviors of nutritionally at risk infants and toddlers in
      Pangalengan, Indonesia. DESIGN: Two cohorts of children were randomly assigned to
      three treatments: E = 1171 kJ + 12 mg iron; M = 12 mg iron + 209 kJ; S = 104
      kJoule. Supplementation was given for 12 months. SETTING: The sites were six tea
      plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (N = 53) and an
      18-month-old (N = 83) cohort were recruited from day-care-centers. Twenty
      children who received S belonged to the 12- and 18-month-old cohort. Inclusion
      criteria were: no chronic disease; length-for-age < or = -1 standard deviation
      (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the
      reference of the World Health Organization. METHODS: Evaluations of intake were
      made at baseline and every 2 months thereafter. Motor development was assessed
      with the Bayley Scale and with a custom-made scale to assess gross motor
      development leading to bipedal locomotion. Four hours of continuous observations
      were made of the child's interaction with the social and physical environment.
      RESULTS: In the 12-month-old cohort, as compared with the M and S groups, the
      children who received the E supplement walked at an earlier age, had higher
      scores in the Bayley Scale and showed more mature social-cognitive and emotional
      regulatory behaviors. Similar intergroup differences were observed in the 18
      month-old cohort in social cognition and regulation of emotions.

PMID- 10902993
TI  - A developmental view of the effects of an energy and micronutrient supplement in
      undernourished children in Indonesia.
AB  - OBJECTIVES: This paper presents the results of a structural equation model
      testing whether the longitudinal data of the Pangalengan subjects fit the
      theoretical model regarding the intellectual delay of undernourished children.
      DESIGN: Two cohorts of children were randomly assigned to three treatments: E =
      1171 kJ + 12 mg iron; M = 12 mg iron + 209 kJ; S = 104 kJ. Supplementation was
      given for 6 months. SETTING: The sites were six tea plantations in Indonesia.
      SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort were
      recruited from day-care-centers. Inclusion criteria were: no chronic disease;
      length-for-age = < 1 standard deviation (s.d.) and weight-for-length between -1
      and -2 s.d. of the median of the reference of the World Health Organization.
      METHODS: Twenty-four-hour dietary intakes were assessed using the weighted
      individual inventory technique. Body weight and length were obtained using
      standard procedures; motor development was assessed with the Bayley Scale and
      with a custom made scale for motor development leading to bipedal locomotion.
      Four-hour observations were made of the child's interactions with the
      environment. Carrying a child in the arms and exploratory behavior were used as
      indicators of caregiving and exploration. All measurements were obtained every 2
      months. RESULTS: The original model did not fit the data. The model was then
      modified with the inclusion of two new pathways: from activity and from motor
      development to mental development. Following these adjustments the model fit the
      data for each cohort and for both cohorts combined.

PMID- 10902995
TI  - Review article: control of gall-bladder motor function.
AB  - Muscular contraction of the gall-bladder is the primary determinant of bile
      delivery into the duodenum. Where bile goes following its secretion by the liver
      depends upon a co-ordinated series of pressure interrelations between the hepatic
      secretory pressure at the entrance to the biliary system, a low pressure conduit,
      and the pressure differences between the gall-bladder, cystic duct and sphincter
      of Oddi. During fasting, the relatively higher tone in the sphincter of Oddi
      fosters the entry of bile into the gall-bladder. The gall-bladder accommodates
      this influx without an increase in intravesicular pressure through its compliance
      or distensibility, which consists of active muscle relaxation and passive
      fibroelastic components. The concentrating function of the gall-bladder keeps the
      volume small. Once about every 120 min during the interdigestive period, gall
      bladder emptying occurs coincident with intense duodenal contractions; all part
      of the migratory myoelectric complex. This helps maintain the enterohepatic
      circulation of bile salts. Motilin, which mediates these events during fasting,
      acts by stimulating intrinsic cholinergic nerves. Cholecystokinin is the major
      determinant of gallbladder emptying with eating. Cholecystokinin acts through pre
      ganglionic cholinergic nerves, to initiate gall-bladder contraction. Agonists
      like cholecystokinin and acetylcholine cause contraction of gall-bladder smooth
      muscle through signal transduction, which increases intracellular calcium levels
      and so initiates the contractile machinery. Cholecystokinin also acts on the
      sphincter of Oddi via pre-ganglionic cholinergic nerves to release vasoactive
      intestinal polypeptide and nitric oxide, and so lower tone. These events are co
      ordinated with motility and secretory events in the upper gastrointestinal tract,
      delivering bile at appropriate times into the duodenum.

PMID- 10902994
TI  - Effects of an energy and micronutrient supplement on iron deficiency anemia,
      physical activity and motor and mental development in undernourished children in
      Indonesia.
AB  - OBJECTIVES: This paper reports the effects of an energy and micronutrient
      supplementation on mental and motor development, activity and behavior under
      natural conditions of children classified as iron deficient anemic and iron
      replete. DESIGN: Children were randomly assigned to two different nutritional
      supplements: (1) 12 mg iron + either 1171 or 209 kJ; (2) 104 kJ + 0 iron.
      Treatment lasted for 6 months. SETTING: The sites were six tea plantations in
      Pangalengan, West Java. SUBJECTS: Eighteen anemic subjects (hemoglobin < 110 g/L;
      transferrin saturation (TS) < 16%) and 18 matched (sex and age) controls
      (hemoglobin > 110 g/L; TS > 16%) were selected from a pool of children with the
      following characteristics: no chronic disease; length-for-age < or = -1 standard
      deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of
      the reference of the World Health Organization. METHODS: Hemoglobin, ferritin,
      transferrin saturation and erythrocyte protoporphyrin were evaluated before and 6
      months after treatment. The following psychological measurements were obtained at
      baseline and 2, 4 and 6 months later. Mental and motor development was evaluated
      with the Bayley Scale. Motor activity was measured by 4 h continuous observations
      at home and at day care centers. The interactions between the child and its
      social and physical environment were also evaluated during 4 h of observations.
      RESULTS: Anemic children showed faster motor development and greater physical
      activity than the control children did. None of the other tests showed inter
      group differences.

PMID- 10902992
TI  - Effects of an energy and micronutrient supplement on play behavior in
      undernourished children in Indonesia.
AB  - OBJECTIVES: This paper reports the effects of an energy and micronutrient
      supplementation on quantitative and qualitative aspects of play among poorly
      nourished children. At issue is whether the supplement led to a progression in
      complexity of play. DESIGN: Two cohorts of children were randomly assigned to
      three treatments: E = 1171 kJ + 12 mg iron; M = 12 mg iron + 209 kJ; S = 104 kJ.
      Supplementation was given for 6 months. Evaluations of play behavior were
      repeated four times. SETTING: The sites were six tea plantations in Pangalengan,
      West Java. SUBJECTS: The present study utilized a subsample of 55 children
      recruited for the larger Pangalengan project 6 months into the study. Thirty
      eight children were recruited late enough to allow for longitudinal observations.
      The remaining cases were used for cross sectional observations only. Inclusion
      criteria were: no chronic disease; length-for-age < or = -1 standard deviation
      (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the
      reference of the World Health Organization. METHODS: The children were videotaped
      during play. These tapes were coded for eight mutually exclusive categories of
      activities. Four activities coded represented manipulative, relational,
      functional and symbolic play. RESULTS: Treatment did not affect qualitative play.
      Girls that received E increased functional play but boys showed the opposite
      effect. Children in the S group were breastfed more during play as compared to
      the E group. Children in the E group waited less to begin play.

PMID- 10902996
TI  - Review article: epidemiology of gall-bladder disease--role of intestinal transit.
AB  - Recent epidemiological studies have suggested that hyperinsulinaemia may be a
      central factor in the pathogenesis of cholesterol gallstones, explaining a
      probable link with physical inactivity as well as abdominal adiposity. There is
      also increasing evidence for the hypothesis that enrichment of bile with DCA.
      'the colonic bile acid', leads to enrichment of bile with cholesterol. Biliary
      DCA can be raised and lowered by slowing down and speeding up colonic transit,
      respectively. Slow transit is characteristic of non-obese British women with
      gallstones and of non-obese peasants in a gallstone-prone mountain community.
      High biliary DCA predicts recurrence of gallstones and so does laxative usage, a
      pointer to constipation and therefore to slow transit. In some studies, at least,
      a high fibre intake is protective against gallstones. Much else besides fibre
      influences colonic function. Future studies of gallstone aetiology should include
      measurements of colonic function. Measures that speed up colonic transit should
      be tested for their ability to prevent gallstone formation in high-risk
      individuals.

PMID- 10902998
TI  - Review article: in vitro studies of gall-bladder smooth muscle function.
      Relevance in cholesterol gallstone disease.
AB  - The interplay between contraction and relaxation in the gall-bladder muscularis
      leads to appropriate gall-bladder emptying and refilling during fasting and in
      the postprandial state in vivo. Several studies in both human and animal models
      have focused on cellular and molecular events in the gall-bladder wall in health
      and disease in vitro. Principal methods to study gall-bladder smooth muscle
      function include receptor binding studies (at the level of plasmamembranes or
      histological sections), phase contrast microscopy (at the level of isolated
      smooth muscle cells), and tensiometry (at the level of smooth muscle strips or
      the whole gall-bladder). At a very early stage, cholesterol gallstone disease is
      characterized by exposure of the gall-bladder wall to excess of biliary
      cholesterol and the cytotoxic effect of the bile salt deoxycholate. On a long
      term basis, a form of gall-bladder leiomyopathy develops with defects involving
      the mechanisms of signal transduction at the level of plasmamembranes. The end
      stage result is pathological contraction and/or relaxation of smooth musculature,
      impaired gall-bladder motility and gall-bladder stasis, all key factors in the
      pathogenesis of biliary cholesterol crystallization and gallstones.

PMID- 10902997
TI  - Review article: effect of bile salt pool composition on hepatic and biliary
      functions.
AB  - The enterohepatic recirculation of bile salts exerts important regulatory effects
      on many hepatic, biliary and intestinal functions: such regulation is likely to
      depend, to a large extent, on the physical-chemical property of hydrophobicity of
      the recirculating pool. The present review summarizes the main experimental
      evidence carried out by our research group over the past two decades, in the
      attempt to investigate systematically the relationships between structural
      properties and biological effects of bile acids in humans. Hydrophobic bile acids
      (chenodeoxycholic acid, deoxycholic acid), but not hydrophilic acids
      (ursodeoxycholic acid), significantly suppressed hepatic activity of HMG-CoA
      reductase, the limiting step of cholesterol synthesis, and in vivo cholesterol
      7alpha-hydroxylation, the limiting step of bile acid synthesis. The output of
      biliary cholesterol and phospholipid was also directly related to the
      hydrophobicity of the bile acid pool. Finally, treatment with chenodeoxycholic
      acid, but not with ursodeoxycholic acid, significantly decreased gall-bladder
      emptying rates. When turning to the in vitro model of HepG2 cells, hydrophobic
      bile acids were found to induce greater cytotoxic and pro-apoptotic effects. From
      this series of studies, we conclude that the regulatory effects of bile acids on
      the liver and biliary tract are largely dependent on the hydrophobic-hydrophilic
      balance of the recirculating bile acid pool.

PMID- 10902999
TI  - Review article: measurement of gall-bladder motor function in health and disease.
AB  - Normal gall-bladder (GB) motor function plays an important role in the
      enterohepatic circulation of bile acids in health, and abnormal GB motor function
      has serious clinical implications. The old concept that the GB empties gradually
      during meals and fills between meals is still believed by many. This paper
      describes the techniques used in the measurement of GB motor function and
      discusses the information provided by these techniques in health and disease.

PMID- 10903000
TI  - Review article: defects in gall-bladder motor function--role in gallstone
      formation and recurrence.
AB  - The pathogenesis of cholesterol gallstones is now recognized as a multifactorial
      process, including saturation of bile with cholesterol, destabilization of bile
      leading to cholesterol crystals and hypomotility permitting crystal growth, and
      agglomeration and retention of microstones which then grow to macroscopic
      gallstones. In the last 15 years meticulous research has demonstrated convincing
      evidence that many patients with cholesterol gallstone disease have a distinct
      defect in gall-bladder motor function that is induced by bile saturated with
      cholesterol.

PMID- 10903001
TI  - Review article: gall-bladder motility after intestinal surgery.
AB  - There is a close relationship in humans between gall-bladder motility and
      gastrointestinal motility during the fasting state, as well as in the post
      prandial period. Only a minority of publications take this relationship into
      account in the description of biliary dysmotility after various surgical
      procedures. Most publications deal with post-prandial gall-bladder motility or
      with stimulation of gall-bladder contraction from various prokinetic drugs or
      gastrointestinal hormones. Impaired gall-bladder motility has been demonstrated
      after Billroth II gastric resection, pyloroplasty and colectomy, but the
      epidemiological data on the risk of gallstone formation in these patients are too
      scarce and equivocal to recommend prophylactic cholecystectomy. Future studies on
      gall-bladder motility after surgical procedures should include measurements of
      gall-bladder motility during the fasting state, as well as in the post-prandial
      period. The measurements should be related to the migrating motor complexes, and
      this necessitates a simultaneous recording of gastrointestinal motility.

PMID- 10903002
TI  - Review: pathogenesis of gallstones.
AB  - The aim of this article is to review selected aspects of the pathogenesis of
      cholesterol-rich, gall-bladder stones (GBS)--with emphasis on recent developments
      in biliary cholesterol saturation, cholesterol microcrystal nucleation, statis
      within the gall-bladder and, particularly, on the roles of intestinal transit and
      altered deoxycholic acid (DCA) metabolism, in GBS development. In biliary
      cholesterol secretion, transport and saturation, recent developments include
      evidence in humans and animals, that bile lipid secretion is under genetic
      control. Thus in mice the md-2 gene, and in humans the MDR-3 gene, encodes for a
      canalicular protein that acts as a 'flippase' transporting phospholipids from the
      inner to the outer hemi-leaflet of the canalicular membrane. In the absence of
      this gene, there is virtually no phospholipid or cholesterol secretion into bile.
      Furthermore, when inbred strains of mice that have 'lith genes' are fed a
      lithogenic diet, they become susceptible to high rates of GBS formation. The
      precipitation/nucleation of cholesterol microcrystals from supersaturated bile
      remains a critical step in gallstone formation. methods of studying this
      phenomenon have now been refined from the original 'nucleation time' to
      measurement of cholesterol appearance/detection times, and crystal growth assays.
      Furthermore, the results of recent studies indicate that, in addition to
      classical Rhomboid-shape monohydrate crystals, cholesterol can also crystallize,
      transiently, as needle-, spiral- and tubule-shaped crystals of anhydrous
      cholesterol. A lengthy list of promoters, and a shorter list of inhibitors, has
      now been defined. There are many situations where GB stasis in humans is
      associated with an increased risk of gallstone formation--including iatrogenic
      stone formation in acromegalic patients treated chronically with octreotide (OT).
      As well as GB stasis, however, OT-treated patients all have 'bad' bile which is
      supersaturated with cholesterol, has excess cholesterol in vesicles, rapid
      microcrystal mulceation times and a two-fold increase in the percentage DCA in
      bile. This increase in the proportion of DCA seems to be due to OT-induced
      prolongation of large bowel transit time (LBTT). Thus LBTT is linearly related to
      (i) the percentage of DCA in serum; (ii) the DCA pool size; and (III) the DCA
      input or 'synthesis' rate. Furthermore, the intestinal prokinetic, cisapride,
      counters the adverse effects of OT on intestinal transit, and 'normalizes' the
      percentage of DCA in serum/bile. Patients with spontaneous gallstone disease also
      have prolonged LBTTs, more colonic gram-positive anaerobes, increased bile acid
      metabolizing enzymes and higher intracolonic pH values, than stone-free controls.
      Together, these changes lead to increased DCA formation, solubilization and
      absorption, Thus, in addition to the 'lithogenic liver' and 'guilty gall-bladder'
      one must now add the 'indolent intestine' to the list of culprits in cholesterol
      gallstone formation.

PMID- 10903003
TI  - Review article: gall-bladder motor function in obesity.
AB  - A number of epidemiological studies has established obesity as a risk factor for
      gallstone disease. More recently, studies have suggested a relationship between
      gallstone disease and the metabolic syndrome linked to central adiposity, whose
      cardinal feature is represented by hyperinsulinaemia. Studies on fasting gall
      bladder volume in obese subjects show that this parameter correlates with weight,
      body mass index (BMI) and body surface area; however, this is also true for large
      sized non-obese subjects. Gall-bladder volume also correlates with abdominal fat
      and with impaired glucose tolerance. In contrast to the well-established role of
      bile supersaturation in the pathogenesis of gallstones in obesity, data are
      controversial on whether gall-bladder motor function is defective in obese
      subjects. However, studies were heterogeneous for subjects' BMI, emptying
      stimulus, technique used and parameters assessed to evaluate gall-bladder motor
      function. Also, differences in baseline gall-bladder volume may lead to wide
      differences in bile 'washout' effect despite apparently similar percentage
      changes in volume or content. Although post-prandial plasma levels of
      cholecystokinin (CCK) are normal in obese subjects, there is some evidence that a
      sub-group of obese subjects could have decreased sensitivity to CCK, possibly
      mediated by hyperinsulinaemia. Further studies using standard physiological
      stimuli and controlling for glucose tolerance, fasting insulin levels and
      baseline gall-bladder volume are needed to establish the role of gall-bladder
      motor function in the pathogenesis of gallstone disease in obesity.

PMID- 10903004
TI  - Review: low caloric intake and gall-bladder motor function.
AB  - Cholelithiasis is the primary expression of obesity in the hepatobiliary system.
      In obese subjects the risk of developing gallstones is increased due to a higher
      cholesterol saturation of gall-bladder bile. During weight reduction with very
      low calorie diets (VLCD) the incidence of gallstones increases, but the mechanism
      for gallstone formation is not completely understood and several pathogenetic
      mechanisms have been suggested: increased saturation of bile, increased gall
      bladder secretion of mucin and calcium, increased presence of prostaglandins and
      arachidonic acid. Alterations in gall-bladder motility may contribute to
      gallstone formation, but few studies have addressed the issue of gall-bladder
      motility during rapid weight loss and its possible role in gallstone formation.
      VLCD have been associated with a gall-bladder stasis, as a consequence of reduced
      gall-bladder stimulation by low fat content of the diets. A threshold quantity of
      fat (10 g) has been documented to obtain efficient gall-bladder emptying.
      Ursodeoxycholic acid administered during VLCD seems to have a protective role in
      developing a biliary cholesterol crystals. Gall-bladder emptying was lower in
      response to low fat meals with respect to relative higher fat meals, before as
      well as during the VLCD. This may account the possibility of an adaptative
      response of the gall-bladder motility to a given diet regimen. Adequate fat
      content of the VLCD may prevent gallstone formation, maintaining adequate gall
      bladder motility and may be more economic and physiologically acceptable than
      administration of a pharmacological agent.

PMID- 10903006
TI  - Review article: the 'mechanical pumps' and the enterohepatic circulation of bile
      acids--defects in coeliac disease.
AB  - Bile acid pool size is maintained relatively constant at about 3-5 g in healthy
      subjects by two mechanisms, enterohepatic circulation and de novo synthesis of
      bile acids. This latter mechanism compensates for the daily faecal loss (about
      0.2-0.6 g) of bile acids, whereas the bulk of the pool is conserved by the former
      mechanism. The driving forces of the enterohepatic circulation are constituted by
      chemical pumps, including intestinal absorption and hepatic uptake, and by
      mechanical pumps, including gall-bladder and intestinal motility. The latter
      provide the main propulsive forces for bile acids to reach the site of intestinal
      absorption, and by contrast with the very rapid chemical pumps, mechanical pumps
      have storage capacity for the bile acid pool and therefore comprise the slow limb
      of the enterohepatic circulation. In coeliac disease, a disease classically
      described as a malabsorption syndrome associated with mucosal atrophy of the
      small intestine, both gall-bladder and small intestinal motor functions are
      impaired, and in this article we review the mechanisms involved in these defects,
      how they influence the enterohepatic circulation of bile acids, and the evidence
      supporting the concept that both the gall-bladder and the small intestinal motor
      functions represent the main factors affecting the kinetics of the enterohepatic
      circulation.

PMID- 10903005
TI  - Review article: hepatobiliary complications associated with total parenteral
      nutrition.
AB  - Parenteral nutrition is often associated with hepatobiliary complications.
      Hepatic steatosis, intrahepatic cholestasis and biliary sludge are the most
      frequent. Cholestasis predominates in infants, steatosis in adults, and biliary
      sludge in both. Other less frequent complications are steatohepatitis and
      gallstones. All hepatobiliary complications are more likely to occur after
      extended periods of total parenteral nutrition, and are prevented by the
      concomitant consumption of nutrients by the enteral route. The pathogenic causes
      are multiple and only partially known. They include lack of gastrointestinal
      stimuli for biliary secretion and gall-bladder motility, abnormalities in bile
      acid metabolism, the presence of sepsis, and the potentially unfavourable effects
      of individual components in the total parenteral nutrition formulae, including an
      excess of calories. Each potential mechanism and its clinical relevance is
      discussed in this review.

PMID- 10903007
TI  - Review article: gall-bladder motor function in diabetes mellitus.
AB  - Although some controversy exists, diabetic patients generally are thought to have
      a two- to threefold increased risk of cholesterol gallstones. From previous
      studies there is no convincing evidence for a supersaturated bile in diabetics,
      whereas several reports indicate that impaired gall-bladder emptying could be one
      of the important factors in the increased incidence of gallstones in diabetics.
      However, studies of gall-bladder motility in diabetics have yielded conflicting
      results, probably because of substantial heterogeneity in the patients studied,
      emptying stimulus and technique used to assess gall-bladder motor function. The
      mechanism of the gall-bladder emptying abnormality in diabetics is not completely
      understood, although it has been proposed that it could represent a manifestation
      of denervation caused by visceral neuropathy. Based on normal post-prandial
      cholecystokinin release, it can be ruled out that impaired cholecystokinin
      release is the mechanism responsible for reduced gall-bladder emptying in
      diabetics. Other possible explanations for impaired gall-bladder contraction in
      diabetics include a decreased sensitivity of the smooth muscle of the gall
      bladder to plasma cholecystokinin, and/or decreased cholecystokinin receptors on
      the gall-bladder wall.

PMID- 10903009
TI  - Are the new local anesthetics worth their cost?

PMID- 10903008
TI  - Review article: agents affecting gall-bladder motility--role in treatment and
      prevention of gallstones.
AB  - Various agents may either enhance or impair post-prandial gall-bladder motility,
      and they are identified in this review. When studying the impact of medication on
      gall-bladder motility, the effects on interdigestive gall-bladder and intestinal
      motility should also be taken into account. Patients at high risk of gallstone
      disease, and patients who are treated chronically with gall-bladder motility
      inhibiting drugs, may benefit from improved gall-bladder motility using a
      prokinetic agent. However, there are no long-term studies to prove that such a
      strategy prevents gallstone formation.

PMID- 10903010
TI  - Postural post-dural puncture headache. A prospective randomised study and a meta
      analysis comparing two different 0.40 mm O.D. (27 g) spinal needles.
AB  - BACKGROUND: To compare the incidence of postural post-dural puncture headache
      (PPDPH) after spinal anaesthesia using two different 0.40 mm O.D. (27 g) spinal
      needles: pencil-point needle and Quincke needle. In addition, a meta-analysis of
      studies comparing small bore spinal needles with regard to development of PPDPH
      was performed. METHODS: Clinical study: A prospective randomised double-blind
      study was set up to investigate PPDPH after using 0.40 mm pencil-point (Pencan,
      B. Braun) or Quincke (Spinocan, B. Braun) spinal needle. Postoperatively on day 5
      to 7 a telephone interview was conducted in order to reveal postoperative
      complications such as headache and backache. PPDPH was considered present when
      the headache was new to the patient, and demonstrated posture dependence. Meta
      analysis: Electronic database search and manual search of relevant literature
      were performed in order to find randomised control trials comparing equal sized
      (outer diameter, O.D.) spinal needles with different bevel shape. Only studies
      with a proper method and not merely presented as an abstract were included in
      addition to the present clinical study. RESULTS: Out of 313 patients randomised,
      301 were completely followed up, 153 in the pencil-point group and 148 in the
      Quincke group. The two groups were comparable regarding surgical procedures and
      demographic data. Of 15 patients suffering from PPDPH, 12 were found in the
      Quincke group, and 3 in the pencil-point group. The difference was 6.1% (95% CI
      from 1.2 to 12.5%). The meta-analysis of 1131 patients gave a relative risk of
      developing PPDPH of 0.38 (95% CI from 0.19 to 0.75) in the pencil-point group
      compared to the Quincke group. CONCLUSION: A pencil-point-shaped spinal needle
      will significantly reduce PPDPH compared with Quincke-type spinal needles, also
      when small bore needles (0.40 mm O.D.) are used.

PMID- 10903012
TI  - Pain intensity and side effects during titration of morphine to cancer patients
      using a fixed schedule dose escalation.
AB  - BACKGROUND: Considerable dose variations and frequent initial side effects have
      been postulated during start of morphine treatment to patients with pain caused
      by malignant disease. However, to our knowledge, only one previous study has
      reported effective doses in morphine naive cancer patients and no prospective
      evaluation has compared symptoms before with symptoms during morphine titration.
      METHODS: We recruited 40 cancer patients with uncontrolled pain despite receiving
      codeine or dextropropoxyphen. Baseline data were obtained for two days before
      start of morphine titration using a fixed scheduled escalation of immediate
      release (IR) morphine. When a stable morphine dose was achieved, IR morphine was
      replaced with slow-release (SR) morphine in equivalent doses. Intensity of pain
      and side effects were assessed daily. The daily consumption of morphine, rescue
      analgesics and rescue antiemetics were registered. RESULTS: The mean titration
      time to achieve adequate analgesia was 2.3 days (range: 1-6) using a mean daily
      morphine dose of 97 mg (range: 60-180). Nausea was unaltered after start with
      morphine but an increased incidence of vomiting occurred (premorphine period 5%,
      IR morphine period 29%). Transient sedation delayed dose increment in 9 of the 40
      patients but mean sedation scores were unaltered. Constipation scores increased
      while other side effect scores were unaltered. Eighty-two percent of the patients
      were satisfied or very satisfied with the pain treatment during introduction of
      morphine. CONCLUSION: In cancer patients with uncontrolled pain on weak opioids,
      successful titration of morphine is achieved fast, with a three-fold morphine
      dose variation and with little increase in side effects.

PMID- 10903011
TI  - The dissociation of sedative from spinal antinociceptive effects following
      administration of a novel alpha-2-adrenoceptor agonist, MPV-2426, in the locus
      coeruleus in the rat.
AB  - BACKGROUND: MPV-2426 is a novel alpha-2-adrenoceptor agonist developed for spinal
      pain therapy. In the present study we characterized its sedative and
      antinociceptive properties following microinjections into the brainstem and
      intrathecally at the lumbar spinal cord level. METHODS: Sedative effects of MPV
      2426 were assessed in a locomotion measuring device following unilateral
      microinjection into the locus coeruleus (LC) of the brainstem or 1-2 mm rostral
      to the LC in rats. Antinociceptive effects induced by MPV-2426 in the brainstem,
      and for comparison intrathecally at the lumbar spinal cord level, were determined
      with a tail-flick test. Dexmedetomidine was used as the reference alpha-2
      adrenoceptor agonist. RESULTS: MPV-2426 produced a dose-related
      hypolocomotive/sedative effect, which was significantly stronger following
      microinjection into the LC than 1-2 mm rostral to the LC. The sedation induced by
      MPV-2426 was reversed by atipamezole (1 mg/kg s.c.), an alpha-2-adrenoceptor
      antagonist. The sedative potency of dexmedetomidine, the reference alpha-2
      adrenoceptor agonist, was stronger and less dependent on the exact injection site
      in the brainstem. Following microinjections at sedative doses in the brainstem,
      only dexmedetomidine produced a significant antinociceptive effect in the tail
      flick test. When microinjected into the lumbar spinal cord, MPV-2426 and
      dexmedetomidine had an equally strong antinociceptive effect in the tail-flick
      test. CONCLUSION: The results indicate that the sedative potency of MPV-2426 is
      considerably weaker than that of dexmedetomidine. Additionally, the spread of MPV
      2426 within the central nervous system is more limited than that of
      dexmedetomidine. This could explain why MPV-2426 is sedative only when injected
      into the LC while antinociceptive effect is obtained when it is injected
      intrathecally at the lumbar spinal cord level.

PMID- 10903013
TI  - Marked enhancement of anti-allodynic effect by combined intrathecal
      administration of the adenosine A1-receptor agonist R-phenylisopropyladenosine
      and morphine in a rat model of central pain.
AB  - BACKGROUND: There is often no satisfactory treatment for chronic pain after
      spinal cord injury. We have previously reported that intrathecal (i.t.)
      administration of the adenosine A1-receptor agonist R-phenylisopropyl-adenosine
      (R-PIA) or the opioid morphine has anti-allodynic effects in a model of presumed
      chronic central pain after photochemically induced spinal cord injury in rats. In
      the present study, we set out to investigate the possible interaction between
      i.t. R-PIA and morphine in spinally injured rats. METHODS: Sprague-Dawley rats
      displaying allodynia-like behaviors to mechanical and cold stimuli after
      photochemically induced spinal cord injury with minor motor deficits were used. R
      PIA and morphine, either alone or in combination, were administered i.t. through
      an implanted catheter to lumbar spinal cord. RESULTS: Cumulative doses of R-PIA
      or morphine dose-dependently reduced the mechanical allodynia-like behavior, with
      a threshold of 1 nmol and 1.5 nmol, respectively. When co-administrated, R-PIA
      and morphine produced marked suppression of mechanical allodynia at doses of 5
      pmol and 7.5 pmol, respectively. The effect of i.t. co-administration of R-PIA
      and morphine on cold allodynia was comparable to i.t. R-PIA alone. The
      combination of R-PIA and morphine did not increase adverse effects such as motor
      deficits in comparison to either drug alone. CONCLUSION: These results
      demonstrate a supra-additive interaction between the adenosine A1-receptor
      agonist R-PIA and morphine to reduce mechanical allodynia-like behavior in rats
      with chronic spinal cord injury. The combination of R-PIA and morphine
      administered spinally may be superior to R-PIA or morphine alone for treating
      such pain.

PMID- 10903014
TI  - Local infiltration with NSAIDs for postoperative analgesia: evidence for a
      peripheral analgesic action.
AB  - BACKGROUND: In order to investigate the evidence for a peripheral analgesic
      effect of local infiltration with nonsteroidal antiinflammatory drugs (NSAIDs) in
      postoperative pain, we conducted a systematic review. METHODS: Randomised
      controlled and double-blind trials were evaluated. Outcome measures were pain
      scores, the use of supplementary analgesics, and time to first analgesic request.
      Efficacy was estimated by significant difference (P<0.05) as reported in the
      original reports and by calculation of the weighted mean difference of pain
      scores between treatment groups. RESULTS: Sixteen studies with data from 844
      patients were considered appropriate for analysis. The NSAIDs were administered
      as intra-articular injections, as components of intravenous regional anaesthesia
      (IVRA), and by wound infiltration and were compared with systemic administration
      or placebo. In the four studies comparing intra-articular NSAIDs with systemic
      administration a statistically significant effect in favour of intraarticular
      NSAIDs was found. Only one study compared IVRA NSAID with systemic
      administration, showing a significant effect in favour of IVRA administration. No
      more than two of the five studies comparing intrawound NSAIDs with systemic
      administration showed significant effect after intrawound administration. Most of
      the studies comparing local infiltration with placebo showed significant effect
      in favour of local infiltration. CONCLUSION: There is evidence for a clinically
      relevant peripheral analgesic action of intra-articular NSAIDs while results of
      IVRA and wound infiltration with NSAIDs in postoperative pain are inconclusive.
      Trials without a systemic control group were not considered to provide evidence
      for a local effect.

PMID- 10903015
TI  - Epileptiform EEG during sevoflurane mask induction: effect of delaying the onset
      of hyperventilation.
AB  - BACKGROUND: Hyperventilation during sevoflurane-N2O-O2 mask induction in adults
      is associated with a hyperdynamic circulatory response and epileptiform
      electroencephalogram (EEG). We tested the hypothesis that delaying onset of
      hyperventilation will prevent severe (periodic) epileptiform EEG and hyperdynamic
      response. METHODS: Thirty patients were randomized to receive either delayed
      (group D, n=15) or immediate (group I, n=15) onset of hyperventilation during
      sevoflurane (8% in N2O 50%) mask inhalation induction with single-breath method
      for unconsciousness. Fifteen patients were allowed to breathe spontaneously for 2
      min after loss of consciousness and controlled hyperventilation (ETCO2 <4%) was
      started thereafter. In 15 patients controlled hyperventilation was started
      immediately after loss of consciousness. EEG was recorded, and mean arterial
      pressure (MAP) and heart rate (HR) registered. RESULTS: Epileptiform EEG patterns
      were seen in 13 patients in group I and in 9 patients in group D (n.s.). Periodic
      epileptiform discharges (PED) tended to occur more often in group I (P=0.07).
      Heart rate and MAP were higher in group I than in group D from 2 min to 3 min (P
      < 0.05), and both HR and MAP rose significantly from the baseline in group I. In
      group D, HR but not MAP rose significantly from baseline. CONCLUSION: Regardless
      of its timing, hyperventilation at a high sevoflurane concentration produced
      severe epileptiform EEG with a hyperdynamic response. PED tended to occur more
      often with immediate onset of hyperventilation.

PMID- 10903016
TI  - Remifentanil and propofol without muscle relaxants or with different doses of
      rocuronium for tracheal intubation in outpatient anaesthesia.
AB  - BACKGROUND: The use of muscle relaxants in outpatient anaesthesia is
      controversial; some authors recommend an induction regimen including propofol and
      opioids without muscle relaxants. This study evaluated the requirements for
      rocuronium after remifentanil/propofol. METHODS: We examined in four groups of
      ASA I-II patients (n= 30 for each) the intubating conditions three minutes after
      induction of anaesthesia with remifentanil 0.5 microg kg(-1) min(-1), propofol 2
      mg kg(-1) without muscle relaxants or with different doses of rocuronium (0.6 mg
      kg(-1), 0.45 mg kg(-1), 0.3 mg kg(-1)) applying the criteria proposed by the
      Copenhagen Consensus Conference. In the second part of the study the time course
      of neuromuscular block was determined by electromyography using train-of-four
      (TOF) stimulation. To this end, another 60 ASA I-II patients were randomly
      assigned to receive remifentanil 0.5 microg kg(-1) min(-1), propofol 2 mg kg(-1)
      and either rocuronium 0.6 mg kg(-1), 0.45 mg kg(-1), 0.3 mg kg(-1), or 0.3 mg kg(
      1) followed by neostigmine 40 microg kg(-1) and atropine 20 microg kg(-1) at a T1
      recovery of 10% (n=15 for each). RESULTS: Intubating conditions were good or
      excellent in 30 patients after rocuronium 0.6 mg kg(-1) and in 18 patients when
      rocuronium was omitted (P<0.01). After 0.45 mg kg(-1) and 0.3 mg kg(-1)
      rocuronium the numbers were 29 and 30 patients, respectively. Reducing rocuronium
      from 0.6 mg kg(-1) to 0.45 mg kg(-1) or 0.3 mg kg(-1) increased the onset time
      from 136 (35) s to 199 (34) s and 249 (52) s (mean (SD)), (P<0.01); the clinical
      duration decreased from 38 (10) min to 24 (8) min and 16 (5) min, respectively
      (P<0.01); and the duration to a TOF-ratio of 0.8 decreased from 60 (11) min to 45
      (9) min and 34 (7) min (P<0.01). After rocuronium 0.3 mg kg(-1) this time
      interval further decreased to 22 (3) min when neostigmine was given at a T1 of
      10% (P<0.01 compared with spontaneous recovery after rocuronium 0.3 mg kg(-1)).
      CONCLUSION: After remifentanil/propofol intubation conditions were poor in 40% of
      patients without muscle relaxants; adding reduced doses of rocuronium to this
      regimen improved the intubation conditions significantly. In addition, reducing
      the initial dose of rocuronium markedly shortened its time course of action.

PMID- 10903017
TI  - Esmolol cardioplegia in unstable coronary revascularisation patients. A
      randomised clinical trial.
AB  - BACKGROUND: Esmolol has been studied and applied to control hypertension and
      tachycardia during open heart surgery. Esmolol has been used on a minor scale as
      a single cardioplegic agent. Little information is available on esmolol as a
      component of blood cardioplegia. In this prospective, randomised, double-blind
      clinical study we investigated whether esmolol improves cardioprotection in
      patients scheduled for an urgent coronary operation. METHODS: Forty patients with
      unstable angina were operated using cold blood cardioplegia as the basic
      cardioprotective method. Cardioplegia was infused intermittently, and esmolol was
      given into the cardioplegia line (15 mg/min) during cold infusions. Patients with
      ongoing myocardial infarction were excluded. RESULTS: The arrest time during the
      cardioplegic induction or the rate of spontaneous resumption of the heart rhythm
      did not differ significantly between the groups. The serial measurements of
      plasma creatine kinase MB-fraction activity (P=0.27), serum creatine kinase MB
      fraction mass assay (P=0.16), troponin I (P=0.41) and myoglobin (P=0.14)
      similarly did not differ between the groups, nor did myocardial lactate
      extraction (P= 0.12). CONCLUSION: Esmolol addition to blood cardioplegia did not
      increase the efficacy of cardioprotection in the present study setting in
      unstable patients during urgent coronary revascularisation.

PMID- 10903018
TI  - Topical tenoxicam from pharyngeal pack reduces postoperative sore throat.
AB  - BACKGROUND: One puff of beclomethasone inhaler has been shown to reduce the
      incidence of sore throat following endotracheal intubation. The aim of this study
      was to determine the effect of a pharyngeal pack on the incidence of sore throat
      and whether tenoxicam-impregnated gauze pack significantly influenced the
      frequency of sore throat. METHODS: Eighty patients undergoing general anaesthesia
      for elective surgery of the nasal septum were evaluated. The anaesthetist sprayed
      the upper airway towards the trachea with one puff of beclomethasone inhaler (50
      microg) before orotracheal intubation. Patients were randomly assigned to have
      either a 0.2% tenoxicam- or a 0.9% saline-impregnated gauze pack in the
      oropharynx during operation. They were evaluated for occurrence and severity of
      postoperative sore throat by direct questions 12-24 h after surgery. RESULTS:
      Four patients who experienced any symptoms in the tenoxicam group scored mild
      sore throat compared to 16 patients in the control group scoring mild, gradually
      developing moderate or severe sore throat (P<0.01). No drug-related side effects
      were observed. CONCLUSION: The intraoperative use of a tenoxicam-impregnated
      gauze pack is effective in reducing moderate or severe postoperative sore throat
      following the use of throat pack.

PMID- 10903020
TI  - Changes in rapidly extracted auditory evoked potentials during tracheal
      intubation.
AB  - BACKGROUND: One of the problems encountered in assessment of the hypnotic level
      during anesthesia is the extraction of a consistent and reliable measure online
      and close to real time. Hemodynamic parameters such as heart rate and blood
      pressure are not, at least with the traditional single parameter versus time
      presentation, adequate for ensuring an optimal level of anesthesia, especially
      when using neuromuscular blocking agents (NMBA). In the literature, it has been
      demonstrated that auditory evoked potentials (AEP) are able to provide two
      aspects relevant to determining level of anesthesia: firstly, they have
      identifiable anatomical significance and, secondly, their characteristics reflect
      the way the brain perceives a stimulus. METHODS: The aim of this study was to
      evaluate the AEP index based on a system identification model, the autoregressive
      model with exogenous input (ARX-model), and to compare it to the classical
      method, the moving time average (MTA). The ARX enables the extraction within 15
      25 sweeps, depending on the signal-to-noise ratio (SNR), whereas MTA typically
      needs 250-500 sweeps. The hypothesis of the present study was that since the ARX
      model extracts the AEP faster than the MTA-model, the former should be able to
      detect changes during the brief, intense stimulus of endotracheal intubation.
      Twelve female patients scheduled for gynecological surgery were included in the
      study. Anesthesia was initiated with thiopentone and maintained with isoflurane
      and alfentanil. The AEP was mapped into an index (AEP-index) normalized to 100
      when the individual was awake and decreasing to an average of 25 during
      thiopentone induced anaesthesia. The results were compared to those obtained by
      MTA-extracted AEP. RESULTS: During tracheal intubation 9 patients showed an
      increase in the ARX-extracted AEP-index larger than 15, and 6 of these patients
      showed an increase larger than 25 (mean increase=33, SD=18). The MTA-extracted
      AEP-index showed only one patient with an increase larger than 15. The ARX
      extracted AEP changed significantly faster than the MTA-extracted AEP.
      CONCLUSION: The ARX-extracted AEP-index increases during tracheal intubation.
      There is a significant difference between the ARX-extracted AEP and the
      traditional MTA-extracted AEP, in terms of response time. In order to trace short
      lasting changes in the hypnotic level by AEP, the AEP should be extracted by a
      method with a fast response such as the ARX-model.

PMID- 10903019
TI  - Preoperative treatment with recombinant human erythropoietin or predeposit of
      autologous blood in women undergoing primary hip replacement.
AB  - BACKGROUND: Controversy exists about the advantages of predeposit of autologous
      blood (PDAB), and whether more comfortable blood conservation regimens may yield
      comparable results. To test the hypothesis that preoperative treatment with
      recombinant human erythropoietin (rHuEPO) with or without acute concomitant
      normovolaemic haemodilution (ANHD) is as effective as PDAB in reducing allogeneic
      blood transfusions, we conducted a prospective randomised study in women
      undergoing primary hip replacement. METHODS: Sixty consecutive female patients
      scheduled for primary hip replacement and suitable for PDAB were randomly
      assigned to one of 3 groups. Group I (EPO) and II (ANHD) received 600 U/kg rHuEPO
      s.c. and 100 mg iron saccharate i.v. on day 14 and, if needed, on day 7 before
      surgery. Additionally, in group II acute normovolaemic haemodilution (ANHD) was
      implemented after induction of anaesthesia. In group III (PDAB) conventional PDAB
      up to 3 U, without volume replacement but with concomitant oral iron therapy, was
      performed starting 4 weeks before surgery. RESULTS: The blood conservation
      methods resulted in a comparable net gain of red cells in all 3 groups until the
      day of surgery. Because of the withdrawal of autologous blood, haemoglobin values
      before surgery were lower in the PDAB group than in the EPO and ANHD groups, and
      during surgery were lower in the PDAB and ANHD groups than in the rHuEPO-only
      group. Applying moderate ANHD in conjunction with preoperative rHuEPO treatment
      did not yield an incremental decrease in allogeneic transfusions. There was no
      difference between the groups in the number of patients who received allogeneic
      transfusions or in the total number of allogeneic units transfused. CONCLUSIONS:
      Withdrawal of autologous blood is associated with lower pre- and intraoperative
      haemoglobin levels when compared to preoperative augmentation of red cell mass
      using rHu-EPO. As a measure to reduce allogeneic transfusion requirements,
      preoperative treatment with rHuEPO may be as effective as standard predeposit of
      autologous blood in women undergoing primary hip replacement, but requires less
      preoperative time.

PMID- 10903021
TI  - Total versus tube-related additional work of breathing in ventilator-dependent
      patients.
AB  - BACKGROUND: In tracheally intubated or tracheostomized spontaneously breathing
      patients, tube resistance can highly increase the patient's work of breathing. In
      this study we focused upon the relationship between total (WOBtot) and tube
      related additional inspiratory work of breathing (WOBadd) and compared different
      ventilatory modalities for proper tube compensation. METHODS: In ten
      tracheostomized spontaneously breathing patients we measured WOBtot and WOBadd in
      the continuous positive airway pressure (CPAP) mode, under inspiratory pressure
      support of 5, 10, and 15 cmH2O in the pressure support ventilation (PSV) mode,
      and under flow-adjusted pressure support in the automatic tube compensation (ATC)
      mode. WOBadd and WOBtot were calculated on the basis of measured tracheal
      pressure and esophageal pressure, respectively. Inspiratory peak tracheal
      pressure above PEEP was taken as an estimate of pressure support beyond mere tube
      compensation (i.e., overcompensation). RESULTS: The percentage of the tube
      related WOBadd on WOBtot in the CPAP mode was 52%. It decreased with increasing
      pressure support in the PSV mode from 32% (PSV 5 cmH2O) to 17% (PSV 15 cmH2O).
      WOBadd was only 15% of WOBtot in the ATC mode. In contrast to the other
      ventilatory modes, reduction of WOBadd in the ATC mode was achieved with the
      smallest amount of overcompensation, i.e. with minimal pressure assist beyond
      mere tube compensation. CONCLUSION: In tracheally intubated or tracheostomized
      spontaneously breathing patients, adequate compensation of tube resistance (i.e.
      with minimal overcompensation and minimal undercompensation) is best done by the
      ATC mode.

PMID- 10903022
TI  - Suppression of surgical hyperaldosteronism by potassium canrenoate during
      gynecologic surgery under sevoflurane anesthesia.
AB  - BACKGROUND: Surgical hyperaldosteronism leads to sodium and water retention
      during surgery and often causes postoperative edema. This study investigated the
      effect of potassium canrenoate (PC) on pituitary adrenocortical function in lower
      abdominal surgery under sevoflurane anesthesia. METHODS: Twenty patients were
      randomized to receive 400 mg of PC (the PC group, n=10) or saline (the control
      group, n=10) intravenously. The following parameters were determined: plasma
      aldosterone, adrenocorticotropic hormone (ACTH), plasma renin activity (PRA),
      serum sodium and potassium, urinary sodium and potassium, and urine output.
      RESULTS: The aldosterone and ACTH levels showed significant increases in the
      control group during surgery. Plasma ACTH also increased significantly in the PC
      group, but plasma aldosterone levels were unchanged during surgery. The urine
      Na/K ratio of the PC group was significantly higher than that of the control
      group. CONCLUSION: The present study suggested that PC suppresses the increase of
      plasma aldosterone caused by surgical stress. That may prevent sodium retention
      and potassium excretion during surgery.

PMID- 10903024
TI  - Use of the laryngeal mask for placement of a bronchial blocker in children.
AB  - For one-lind ventilation in children, a bronchial blocker (e.g. Fogarty catheter)
      is often used, but its insertion may not be easy. We report a new method of
      placement of a bronchial blocker in an infant, using the laryngeal mask.

PMID- 10903023
TI  - Comparative effect of amrinone, aminophylline and diltiazem on rat airway smooth
      muscle.
AB  - We investigated the effect of amrinone, a phosphodiesterase III inhibitor, on rat
      airway smooth muscle, and thereafter, compared its activity with aminophylline
      and diltiazem. Amrinone produced relaxation of the acetylcholine-induced airway
      contraction in a dose-related manner. This bronchodilatory activity of amrinone
      was similar to that of aminophylline, but smaller than that of diltiazem. The 50%
      relaxant effect (ED50) of amrinone, aminophylline and diltiazem were 3.6 x 10(-4)
      M, 1.4 x 10(-4) M and 1.4 x 10(-5) M, respectively. Diltiazem was the most potent
      airway relaxant, and amrinone was less potent in these experiments. Taken
      together in its positive inotropic and chronotropic effects and anti-inflammatory
      activity, however, amrinone could be beneficial for treatment of patients
      suffering from asthma or heart failure with cardiac asthma.

PMID- 10903025
TI  - Cisplatin toxicity in the rat may be influenced by anaesthetic agents.

PMID- 10903026
TI  - Synthesis of glycosyl(thio)ureido sugars via carbodiimides and their
      conformational behaviour in water.
AB  - The preparation of sugar ureas and thioureas by nucleophilic addition of water or
      hydrogen sulfide, respectively, to sugar-derived carbodiimides has been examined.
      Acetic acid efficiently catalysed the formation of ureas, whereas silica gel was
      found to be a more convenient catalyst in the case of the thioxo analogues. The
      procedures have been exploited in the development of an amine- and isocyanate
      free synthesis of urea- and thiourea-tethered pseudooligosaccharides via the
      corresponding glycosylcarbodiimido sugars. The fully unprotected compounds
      adopted, preferentially, the (Z,Z) configuration at the pseudoamide bonds in
      water solution.

PMID- 10903028
TI  - The structure of the core part of Proteus penneri strain 16 lipopolysaccharide.
AB  - The structure of the carbohydrate backbone of the lipid A-core region of the
      lipopolysaccharide (LPS) from Proteus penneri strain 16 was determined using NMR
      and chemical analysis of the core oligosaccharide, obtained by mild acid
      hydrolysis of the LPS, and of the products of alkaline deacylation of the LPS:
      formula [see text]. Incomplete substitution is indicated by bold italics. All
      sugars are in the pyranose form, alpha-Hep is the residue of L-glycero-alpha-D
      manno-Hep, alpha-DD-Hep is the residue of D-glycero-alpha-D-manno-Hep, Bu is the
      (R)-3-hydroxybutyryl residue.

PMID- 10903027
TI  - Sucrose tricarboxylate by sonocatalysed TEMPO-mediated oxidation.
AB  - Oxidation of sucrose by the NaOCl/TEMPO system provided sucrose tricarboxylate
      without the addition of sodium bromide as co-catalyst when high-frequency (500
      kHz) ultrasound was applied, in contrast to very limited conversion without
      sonication. In the presence of sodium bromide, sonication also caused
      acceleration of the oxidation. The rate increase due to sonication of the oxidant
      system prior to sucrose addition suggests that ultrasound acts at the level of
      the formation of the nitrosonium ion, the active oxidising species in the
      catalytic cycle.

PMID- 10903029
TI  - Computational studies on carbohydrates: in vacuo studies using a revised AMBER
      force field, AMB99C, designed for alpha-(1-->4) linkages.
AB  - Modifications to the AMBER force field [W.D. Cornell, P. Cieplak, C.I. Bayly,
      I.R. Gould, K. Merz, D.M. Ferguson, D.C. Spellmeyer, T. Fox, J.W. Caldwell, P.A.
      Kollman, J. Am. Chem. Soc., 117 (1995) 5179-5197] have been made to improve our
      ability to reproduce observed molecular properties of alpha-linked carbohydrates
      when calculated using empirical potential-energy functions. Molecular structures
      and energies obtained using gradient-optimized density functional methods with ab
      initio basis sets (B3LYP/6-31G*) on ten minimum-energy conformations of maltose
      [F.A. Momany, J.L. Willett, J. Comp. Chem., submitted for publication] were used
      to refine the empirical potentials. Molecular dynamics simulations on beta
      maltose (i.e., the beta anomer of maltose), cyclohexamylose (alpha-cyclodextrin),
      cycloheptamylose (beta-cyclodextrin) and larger cyclomaltooligosaccharide
      structures were carried out and compared with experimental structural studies to
      test the new potentials. Ring-puckering potential during dynamics as well as
      conformational transitions to 'flipped' structures were examined. Results of the
      tests described here suggest that the revised AMBER parameters (AMB99C) are very
      good for computational studies of alpha-(1-->4)-linked carbohydrates.

PMID- 10903030
TI  - Computational studies on carbohydrates: solvation studies on maltose and
      cyclomaltooligosaccharides (cyclodextrins) using a DFT/ab initio-derived
      empirical force field, AMB99C.
AB  - An empirical force field, denoted AMB99C, has been used to study molecular
      properties of alpha-(1-->4)-linked carbohydrates in solution. AMB99C was
      parameterized using structural and energetic parameters from density functional
      ab initio methodology. In this work we examine the solution behavior of the beta
      anomer of maltose and cyclohexa-, cyclohepta-, and cyclooctaamyloses (alpha-,
      beta-, and gamma-cyclodextrins or alpha-, beta-, and gamma-CDs, respectively), as
      well as of two larger (DP 10, epsilon-CD; DP 21) cyclomaltooligosaccharides, CA10
      and CA21. Experimental data used for comparison purposes include X-ray
      structures, small-angle scattering radius of gyration values, NMR nuclear
      Overhauser enhancements (NOEs), and proton coupling constants. Molecular dynamics
      simulations were carried out using explicit water molecules (TIP3P) to establish
      equilibrium populations of conformations in solution, and these results are
      compared with other calculated values and a variety of experimental parameters,
      such as average H-1-H-4' distances between the rings in beta-maltose, and the
      primary hydroxyl groups' conformational populations. Medium-to-large
      cyclomaltooligosaccharide molecules were studied to test for glucose ring
      puckering and stability of kinked and 'flipped' conformations. The results of the
      solvation studies are in excellent agreement with experimental structural
      parameters.

PMID- 10903031
TI  - Molecular dynamics simulations of cyclohenicosakis-[(1-->2)-beta-D-gluco
      henicosapyranosyl], a cyclic (1-->2)-beta-D-glucan (a 'cyclosophoraose') of DP
      21.
AB  - We report molecular dynamics simulations of cyclohenicosakis-[(1-->2)-beta-D
      gluco-henicosapyranosyl], termed 'cyclosophohenicosamer', a member of a class of
      cyclic (1-->2)-beta-D-glucans ('cyclosophoraoses'). Our goals were to provide
      insights into the conformational preferences of these cyclosophoraoses. Simulated
      annealing and constant-temperature molecular dynamics calculations were performed
      on the DP 21 cyclosophohenicosamer. The radius of gyration (R(G)) of the molecule
      and the conformation of glycosidic dihedral angles were used to analyze the
      result of computational studies. Most glycosidic linkages were concentrated in
      the lowest-energy region of the phi-psi energy map, and the values of radius of
      gyration from our simulations were consistent with the reported experimental
      value. The simulations produced various types of compact and asymmetric
      conformations within reasonable ranges of the glycosidic linkage conformation and
      radius of gyration. The results indicate the presence of a high degree of
      molecular flexibility of cyclosophohenicosamer and suggest the uniqueness of
      inclusion complexation with other molecules through this molecular flexibility.

PMID- 10903032
TI  - A facile synthesis of 1-(5'-O-acetyl-3'-O-benzyl-beta-D-xylofuranosyl)thymidine:
      a potentially viable intermediate for the preparation of the anti-AIDS drugs, AZT
      and D4T.
AB  - The title compound has been synthesized by smooth condensation of 1,2-anhydro-5-O
      acetyl-3-O-benzyl-alpha-D-xylofuranose, obtained from D-xylose through a series
      of mild and effective reactions, with activated thymine in the absence of
      catalyst.

PMID- 10903033
TI  - Study of cellular responses to polymeric biomaterials using the differential
      display method.
AB  - In this study, we attempted to detect altered gene expressions in the cells that
      had adhered to various surfaces using the differential display method.
      Thioglycollate-elicited peritoneal exudate cells (PEC) and mouse fibroblast
      (L929) cells were cultured on the polymer films. After a predetermined time, the
      total RNA was isolated from cells and the differential mRNA expressions were
      evaluated by RT-PCR method. As a result, in the differential display of amplified
      cDNA from PEC, the different patterns of cDNA fragments among the samples were
      obtained. This indicates that there were many different mRNA expressions
      depending on the polymer surfaces. The use of differential method was proven to
      be useful for studying cell-polymer interaction.

PMID- 10903034
TI  - Soft tissue adhesive composed of modified gelatin and polysaccharides.
AB  - Although fibrin glue has been clinically used as a surgical adhesive, hemostatic
      agent, and sealant, it has the risk of virus infection because its components,
      fibrinogen and thrombin, are obtained from human blood. To circumvent this
      problem, we employed bioabsorbable gelatin and polysaccharides to prepare a safer
      hemostatic glue. Gelatin was modified with ethylenediamine using water-soluble
      carbodiimide to introduce additional amino groups into the original gelatin,
      while dextran and hydroxyethyl-starch were oxidized by sodium periodate to
      convert 1,2-hydroxyl groups into dialdehyde groups. Upon mixing of the two
      polymer components in aqueous solution, Schiff base was formed between the amino
      groups in the modified gelatin and the aldehyde groups in the modified
      polysaccharides, which thus resulted in intermolecular cross-linking and gel
      formation. The fastest gel formation took place within 2 s, and its bonding
      strength to porcine skin was about 225 gf cm(-2) when 20 wt% of an amino-gelatin
      (55% amino) and 10 wt% of aldehyde-HES (>84% dialdehyde) aqueous solutions were
      mixed. In contrast, the gelation time and bonding strength of fibrin glue was 5 s
      and 120 gf cm(-2), respectively.

PMID- 10903035
TI  - Novel poly(urethane-aminoamides): an in vitro study of the interaction with
      heparin.
AB  - In order to obtain heparin-binding polyurethanes, tertiary amino-groups have been
      introduced in the polymer backbone by attributing a key-role to the chain
      extender, i.e. substituting butanediol, commonly used in polyurethane synthesis,
      with a tailor-made diamino-diamide-diol. In this work a poly(ether-urethane
      aminoamide) (PEU/PIME/al) was obtained with poly(oxytetramethylene) glycol 2000,
      1,6-hexamethylene-diisocyanate and the new chain extender, in the molar ratio
      1:2:1. The heparin binding capacity of PEU/PIME/al was evaluated with 125I
      labelled heparin, using for comparison the analogous polymer obtained with a
      diamide-diol (i.e. the poly(ether-urethane-amide) PEU/PIBLO/al), and two
      commercially available biomedical polyurethanes (Pellethane 2363 and Corethane).
      pH and ionic strength dependence of the heparin uptake were investigated by
      treating all the polyurethanes with solutions of 125I heparin into buffers from
      pH 4 to 9 or NaCl molarity from 0.0 to 1.0. The stability of the interaction with
      bound heparin was investigated by sequential washing treatments (PBS, 1 N NaOH,
      2% SDS solution), then analysing the residual radioactivity on the materials.
      Results indicated that the heparin binding of PEU/PIME/al is significantly higher
      and more stable than that of the other polyurethanes, with a time-dependent
      kinetic. The interaction with heparin appears to be prevalently ionic, with the
      contribution of other electrostatic and hydrophobic interactions. Activated
      partial thromboplastin time (APTT), performed on human plasma with polyurethane
      coated, heparinized test tubes, indicated that bound heparin maintains its
      biological activity after the adsorption.

PMID- 10903036
TI  - Protein A-immobilized microporous polyhydroxyethylmethacrylate affinity membranes
      for selective sorption of human-immunoglobulin-G from human plasma.
AB  - Microporous membranes made of poly(2-hydroxyethylmethacrylate) [poly(HEMA)]
      carrying protein A were used for selective sorption of human-IgG from human
      plasma. Poly(HEMA) membranes were prepared by a photo-polymerization technique,
      and activated by cyanogen bromide (CNBr) in an alkaline medium (pH 11.5).
      Bioligand protein A was then immobilized by covalent binding onto these CNBr
      activated membranes. The amount of immobilized protein A was controlled by
      changing pH and the initial concentrations of CNBr and protein A. The non
      specific adsorption of protein A on the plain poly(HEMA) membranes was 2.9 microg
      cm(-2). Maximum protein A immobilization was observed at pH 9.5. Up to 186 microg
      cm(-2) was immobilized on the CNBr-activated poly(HEMA) membranes. The maximum
      adsorption of human-IgG on the protein A-immobilized poly(HEMA) membranes was
      observed at pH 8.0. The non-specific adsorption of human-IgG onto the plain
      poly(HEMA) membranes was low (about 4.4 microg cm(-2)). Higher human-IgG
      adsorption values (up to 394 microg cm(-2)) were obtained in which the protein A
      immobilized poly(HEMA) membranes were used. Much higher amounts of human-IgG (up
      to 489 microg cm(-2)) were adsorbed from human plasma. Up to 91% of the adsorbed
      human-IgG was desorbed by using 0.1 M aminoacetic acid as elution agent. The
      adsorption-desorption cycle was repeated ten times using the same polymeric
      membranes. There was no remarkable reduction in the adsorption capacity of the
      protein A-immobilized poly(HEMA) membranes.

PMID- 10903037
TI  - Synthesis, chemical and rheological characterization of new hyaluronic acid-based
      hydrogels.
AB  - New hyaluronic acid-based hydrogels have been synthesized. The carboxylate groups
      of hyaluronan were activated in order to bind the amino terminal groups of the di
      amine cross-linking reagent. Different hydrogels were obtained according to the
      different di-amine cross-linking agents (1,3-diaminepropane, 1.6-diaminohexane,
      PEG500 di-amine. and PEG800 di-amine). The cross-linked polymer (C.L.Hyal) was
      then sulphated (C.L.HyalS) by a heterogeneous reaction using sulphur trioxide
      pyridine complex (SO3-Py). The thermo-mechanical properties and swelling degree
      were evaluated and are discussed in relation to the chemical structure and the
      hydrophilic character of the gels. The different behaviours of C.L.Hyal and
      C.L.HyalS indicate the important role of sulphated groups.

PMID- 10903038
TI  - Tissue responses to molecularly reinforced polylactide-co-glycolide implants.
AB  - Plates for internal fixation fabricated from biodegradable polymers degrade via
      an autocatalytic route. When they are used in bone implants of significant size
      and thickness, hollowing of the implant may occur while the overall dimensions
      appear unchanged. We hypothesized that incorporation of a cross-linked
      polypropylene fumarate matrix into polylactide-co-glycolide bone plates may
      provide an internal molecular network which prevents implant collapse. Cross
      linking reagents of varying hydrophilicity including N-vinylpyrrolidone (VP),
      hydroxyethylmethacrylate (HEMA), and ethyleneglycol dimethacrylate (EGDMA) were
      employed. With the objective of determining the most biocompatible and
      structurally sound composition for molecular reinforcement, we investigated
      tissue responses in both subcutaneous and orthotopic rodent implantation models
      in relation to maintenance of implant integrity by histologic, histomorphometric,
      and stereomicroscopic analysis. Results showed that tissue responses were
      correlated with dimensional stability of the implants. The most favorable results
      were seen with the hydrophobic cross-linker EGDMA; this may have been related to
      the initial reduction of the water uptake by the implant. Cross-linking of
      polypropylene fumarate with EGDMA within a polylactide-co-glycolide bone plate
      may offer a means to maintain excellent biocompatibility while improving
      dimensional stability of biodegradable bone plates.

PMID- 10903039
TI  - Immobilized biomolecules on plasma functionalized cellophane. I. Covalently
      attached alpha-chymotrypsin.
AB  - Surface morphology changes of hydrazine-RF-plasma-exposed cellophane surfaces
      were monitored under 40 kHz and 13.56 MHz CW and pulsed discharge environments
      and the immobilization of alpha-chymotrypsin onto plasma-modified substrates was
      studied. It has been shown, using SEM and AFM techniques, that significantly
      different cellophane topographies are generated under different frequency and
      pulsing parameter conditions. ESCA and ATR-FTIR analyses of plasma-modified
      surfaces indicated the presence of primary amide and primary amine
      functionalities. It was found that the relative ratios of crystalline vs
      amorphous zones of the nascent surface layers can also be controlled by properly
      selected plasma parameters, including the duty cycles of pulsed plasma
      environments. Enzyme immobilization reactions with alpha-chymotrypsin were
      accomplished both from oxygen-plasma-generated carbonyl and hydrazine-plasma
      created primary amine functionalities by anchoring the biomolecules either
      directly to the cellophane surface or by involving spacer molecules. It was found
      with the cellulose substrates that fairly good enzyme activity was retained
      without the necessity of intercalated spacer chains. It appears that the ability
      of the cellulose substrate to swell in the aqueous environment allows sufficient
      freedom of mobility for the immobilized enzyme to retain a significant part of
      its activity on the cellulose. However, the activities both of the free enzyme in
      the presence of cellophane, and that of the immobilized enzyme molecules are
      significantly diminished in comparison to the activity of the free enzyme, as a
      result of the incorporation of these molecules into the swollen network.
      Potential applications of immobilized enzymes from cold-plasma-functionalized
      surfaces are discussed.

PMID- 10903040
TI  - Basilar artery and vertigo.
AB  - Our goal was to identify by magnetic resonance angiography the specific vascular
      abnormalities of the basilar artery that can be related to hypoperfusion
      disorders and produce symptoms of vertebrobasilar insufficiency. A classification
      of regional vascular perfusion disorders based on developmental malformations and
      intrinsic and extrinsic angiopathies was formulated from an analysis of
      individuals with these disorders. Specific angiographic abnormalities such as
      tortuosity, stenosis, thrombosis, and dolichoectasia were identified in subjects
      with vestibulocerebellar dysfunction. Charts and radiographic images were
      examined with respect to the history, physical evidence, and vascular
      configuration, and the data were integrated for comprehensive analysis. We found
      that abnormalities identified by magnetic resonance angiography could be
      correlated with symptoms due to vascular insufficiency. Cases are presented that
      document the developmental and acquired arterial disorders that may be considered
      the etiologic factors for regional perfusion deficits.

PMID- 10903041
TI  - Surgical management of uncomplicated otitis media in a pediatric Medicaid
      population.
AB  - The objective of this study was to document the frequency and timing of otitis
      media-related visits, audiological consultations, and surgical interventions
      following a new episode of otitis media. A retrospective descriptive study was
      performed on a Medicaid administrative database that follows individual patients
      over time. The study included 14,453 children enrolled in Medicaid during 1991
      and 1992 who were 30 months of age or younger and had a "new" episode of otitis
      media. Among 14,321 patients with an uncomplicated episode of otitis media, there
      were 10,443 with additional otitis media visits. Audiological testing was
      performed in 1,134 (10.9%). The testing occurred within 2 months of the onset of
      otitis media in 52.2% of the children and within 3 months in 66.6%. Physicians
      referred 400 children (3.8%) to an otolaryngologist; 299 (75%) underwent 1 or
      more surgical procedures. These surgical interventions included placement of
      ventilating tubes in 296 children, adenoidectomy in 34 children (all of whom also
      had placement of ventilating tubes), mastoidectomy in 2 children, and
      tympanoplasty in 1 child. The proportion of children who underwent surgical
      placement of ventilating tubes who had prior audiological testing was 174 of 296
      (58.8%). The overall surgical rate for ventilating tubes was 2.9%. Among children
      who underwent surgery, the procedure occurred within 2 months of the onset of
      otitis media in 21.4% of children. Attempts to rationalize the management of
      otitis media in early childhood must deal with the difficulties in distinguishing
      among the otitis media conditions. The findings of this study suggest a need to
      know whether insertions of ventilating tubes within 3 months after a new episode
      of otitis media are related to unresponsive or recurrent infections.

PMID- 10903042
TI  - Effect of a beta-stimulant on the inner ear stria vascularis.
AB  - In vivo and in vitro experiments were conducted to investigate the effect of
      alpha-isoproterenol on the inner ear stria vascularis with intracellular
      cytochrome oxidase activity used as an index. Intraperitoneal injection of alpha
      isoproterenol (5 mg/kg) was performed in 10 rats, and that of physiological
      saline in 4 rats, for 21 consecutive days. After the 3-week treatment, bilateral
      cochleas were excised for frozen sections and stained for cytochrome oxidase. The
      staining density of the stria vascularis for the enzyme was analyzed with a
      computer. Electron microscopic observation was also performed for some specimens.
      As for the in vitro experiments, bilateral cochleas from 6 normal rats were
      excised for cell culture. Cochlear cells from the right ear were cultured with
      medium containing alpha-isoproterenol (10-micromol/L concentration), and those
      from the left ear with medium alone. After 3-day culture, the enzyme activity of
      cytochrome oxidase in the stria vascularis was quantified by the same method used
      for the in vivo experiments. Cytochrome oxidase activity was markedly elevated in
      the alpha-isoproterenol group. The activity tended to be higher in the lower
      turns of the cochlea. Electron microscopy revealed that numerous mitochondria
      were present in marginal cells that protruded into the endolymphatic space. The
      enzyme activity was also elevated in the stria vascularis from cochlear specimens
      in the alpha-isoproterenol group of the in vitro experiment. The above results
      suggest that alpha-isoproterenol accelerated the metabolic activity of the cells
      that constitute the stria vascularis. The increase in activity was probably
      attributable to direct pharmaceutical effects of the beta-stimulant, rather than
      an increase in blood flow. It is possible that the cells that constitute the
      stria vascularis may have beta-receptors.

PMID- 10903043
TI  - Comparison of functional endonasal sinus surgery with and without partial middle
      turbinate resection.
AB  - The aim of endonasal sinus surgery is to ameliorate sinonasal symptoms and to
      achieve a functional nose. Although the importance of opening the ostiomeatal
      complex is accepted, the role of middle turbinate surgery remains controversial.
      Although some surgeons emphasize the importance of maintaining the middle
      turbinate as a physiological humidifier and anatomic landmark, others resect it
      without adverse sequelae. To date, there have only been limited reviews published
      to support either approach. This paper examines 1,106 matched patients who
      underwent similar functional endonasal sinus surgery with (509 patients) or
      without (597 patients) middle turbinate surgery. We demonstrate a paucity of
      complications and the potential outcome benefits of judicious partial middle
      turbinate resection in some patients with more severe rhinosinusitis.

PMID- 10903044
TI  - Combination of angiogenesis inhibitor TNP-470 with cytotoxic drugs in
      experimental therapy of nasopharyngeal carcinoma.
AB  - This study was conducted to evaluate the effectiveness of angiogenesis inhibitor
      6-O-(N-chloroacetyl-carbamoyl)-fumagillol (TNP-470. AGM-1470) in the treatment of
      nasopharyngeal carcinoma (NPC) alone and in combination with cytotoxic agents.
      Forty-two male BALB/c nude mice bearing human NPC cell line CNE-2 were randomized
      into 6 groups: those treated with saline solution, TNP-470, cisplatin (DDP),
      fluorouracil (5-FU), TNP-470 + DDP, and TNP-470 + 5-FU, respectively. In every
      treatment group, tumor growth was suppressed significantly. The combination of 5
      FU with TNP-470 showed significant enhancement in antitumor efficacy. TNP-470
      also enhanced the inhibitory effect of DDP, although not to statistical
      significance. All animals gained in body weight, although treatment with 5-FU
      caused slight, reversible diarrhea of 2 to 3 days' duration. The results showed
      that TNP-470 suppressed the growth of the human NPC cell line and enhanced the
      antitumor effect of 5-FU without increasing its toxicity. The combination of
      angiogenesis inhibitors with conventional cytotoxic agents is promising in the
      treatment of NPC.

PMID- 10903046
TI  - Ultrastructure of the vocal process of the arytenoid cartilage.
AB  - An investigation of the ultrastructure of the vocal process of the arytenoid
      cartilage was performed on excised human adult larynges. The results are
      summarized as follows. 1) The size of the chondrocytes is small and their density
      is high at the tip of the vocal process. 2) The size of the chondrocytes
      increases and their density decreases toward the posterior portion of the vocal
      process. 3) At the tip of the vocal process, the collagenous fibers are thin and
      run in various directions. 4) The thickness of the collagenous fibers increases
      and they form thick bundles toward the posterior portion of the vocal process. 5)
      The elastic fibers are dense at the tip of the vocal process, and their number
      decreases toward the posterior portion of the vocal process. 6) The elastic
      fibers, which are slender, branched, and anastomosed to form a loose network, run
      among the collagenous fibers at the tip of the vocal process. 7) Elaunin fibers
      are the predominant elastic fibers at the tip of the vocal process. 8) Even in
      the hyaline cartilage portion of the vocal process, elastic fibers are found. 9)
      The vocal processes are firm in forming the framework of the glottis and are more
      pliable toward the tip. 10) The 3-dimensional structure of the gradual changes in
      stiffness between the vocal fold and the vocal process makes a functional
      contribution to the roles of the vocal folds and the vocal processes.

PMID- 10903045
TI  - Lack of predictive value of the Epworth Sleepiness Scale in patients after
      uvulopalatopharyngoplasty.
AB  - The Epworth Sleepiness Scale (ESS) has been recognized as a valid measure of
      sleep propensity. Statistically significant correlations between ESS scores, the
      respiratory disturbance index (RDI), and the lowest arterial oxygen saturation
      (LSAT) have been described in patients with surgically untreated obstructive
      sleep apnea (OSA). We investigated whether the same relationships hold true after
      uvulopalatopharyngoplasty (UPPP). Forty-two adults with documented OSA treated by
      UPPP were reevaluated with the ESS questionnaire and 8-hour diagnostic nocturnal
      polysomnography (nPSG). We found no significant correlation between the ESS
      scores and the RDI or LSAT in patients after UPPP. Because postoperative ESS
      scores do not correlate with the RDI or LSAT, we conclude that the ESS is not a
      reliable surrogate for nPSG testing.

PMID- 10903047
TI  - Recurrent laryngeal nerve monitoring during cricotracheal resection.
AB  - Cricotracheal resection has been advocated in the management of severe subglottic
      stenosis. One of the possible complications of this procedure is injury to the
      recurrent laryngeal nerve (RLN). We describe a new technique in which electrodes
      are placed directly through the thyroid cartilage to monitor the RLN
      intraoperatively. Nine cats' left vocal cords were monitored, and 3 cats had
      unilateral vocal cord injury postoperatively: 1 right cord and 2 left cords. Even
      though this technique was efficacious, our ability to monitor the RLNs was
      difficult secondary to difficulty interpreting the nerve monitor's wave
      morphologies. The future use of RLN nerve monitoring during cricotracheal
      resection will depend upon the ability to distinguish true stimulation from
      artifact. Monitoring of the RLN could be beneficial in patients with previous
      operations for subglottic stenosis.

PMID- 10903048
TI  - Influence of phonation on basement membrane zone recovery after
      phonomicrosurgery: a canine model.
AB  - The process of wound healing at the basement membrane zone of the vocal folds
      after phonomicrosurgery was investigated. The influence of phonation and the
      implied optimal period of voice rest were considered. Phonomicrosurgery was
      performed on both vocal folds of 20 adult dogs. In 10 dogs, the left recurrent
      laryngeal nerve was simultaneously resected to simulate iatrogenic voice rest;
      the remaining 10 dogs were allowed to phonate normally. The healing process of
      the vocal folds of each group was observed at 1, 2, 4, 8, and 12 weeks after
      surgery with immunohistochemical staining and transmission electron microscopy.
      In the voice rest group, the basement membrane was completely re-formed in 2
      weeks, and the "cover" appeared completely rearranged by 8 weeks. The results of
      the phonation group were characterized by a delayed healing process and basement
      membrane changes. These results suggest that voice rest of at least 2 weeks after
      surgery may be beneficial and that vocal hygiene should be maintained for as long
      as 8 weeks.

PMID- 10903049
TI  - Vascular and epidermal effects of fibroblast growth factor on irradiated and
      nonirradiated skin flaps.
AB  - Head and neck cancer surgeons are often faced with the challenge of managing
      previously irradiated soft tissue that has poor vascularity and slower
      epithelialization. This study investigates the effect of supplemental basic
      fibroblast growth factor (bFGF) on flap vascularity, tissue oxygenation, and
      epidermal regeneration in nonirradiated (n = 40) and irradiated porcine skin
      flaps (n = 40). Supplemental bFGF increased vascularity in nonirradiated flaps by
      80% (p = .005), with a trend to a higher tissue oxygen level by day 14. The
      irradiated bFGF-treated flaps did not show increased vascularity or higher tissue
      oxygen levels 2 weeks after surgery. However, in both irradiated and
      nonirradiated groups, epidermal regeneration increased by greater than 70% with
      supplemental bFGF (p < .002). The results of this study suggest that supplemental
      bFGF can increase tissue vascularity in nonirradiated tissues and epidermal
      regeneration in both nonirradiated and irradiated conditions.

PMID- 10903050
TI  - Cervical versus thoracic epidural morphine for the treatment of head and neck
      cancer pain.
AB  - We studied 29 patients in the final stage of head or neck cancer who were
      suffering pain that was not relieved by oral morphine. Cervical or thoracic
      epidural morphine was administered to relieve the pain. The quality of analgesia
      was equally good for both techniques. However, cervical epidural administration
      appeared to be superior, because much smaller doses of morphine were required in
      order to induce more rapid and longer analgesia.

PMID- 10903051
TI  - Cat-scratch disease of the parotid gland: an often-misdiagnosed entity.
AB  - A case of cat-scratch disease involving the parotid area in a young adult is
      presented. Thanks to meticulous history-taking, the correct diagnosis was
      suggested and later established, thus preventing unnecessary surgery. The
      pertinent literature is discussed.

PMID- 10903052
TI  - Liposarcoma of the tongue: case report and literature update.
AB  - Liposarcoma is an exceedingly rare tumor in the oral cavity. We report a case of
      a 70-year-old man with liposarcoma that presented as a lump on the tongue. The
      excised tumor was diagnosed as a well-differentiated lipoma-like liposarcoma. The
      majority of cases of well-differentiated liposarcoma follow a relatively benign
      course, but the disease has a high recurrence rate. It appears that accurate
      clinical and histopathologic diagnosis of this lesion is difficult. The prognosis
      seems to depend on the histologic type, size, and location of the lesion. Wide
      surgical excision is important for successful management of these liposarcomas.

PMID- 10903053
TI  - Airway burns and atelectasis in an adolescent following aspiration of molten wax.
AB  - Scald injuries caused by hot liquids are not a frequently reported cause of
      pediatric respiratory and alimentary tract burns. Aspiration of molten wax with
      subsequent pharyngeal or laryngeal burns has not been described at all, to the
      best of our knowledge. A case of an adolescent who presented with airway burns
      and atelectasis subsequent to aspiration of molten wax is herein described and
      discussed.

PMID- 10903054
TI  - Internal carotid artery aneurysm presenting as a large pharyngeal mass.

PMID- 10903055
TI  - Burkitt's lymphoma: historical background and recent insights into classification
      and pathogenesis.
AB  - In this paper, the authors evaluate the historical evolution of the definition of
      Burkitt's lymphoma (BL) and of its clinicoepidemiological (endemic, sporadic, and
      acquired immunodeficiency syndrome-associated BL) and morphological variants. On
      the basis of the morphological, immunologic, genetic, and clinical
      characteristics of these tumors, the authors also emphasize the importance of
      precise disease definitions for biological and epidemiological studies. These
      principles were used in accordance with the Revised European-American
      classification of lymphoid neoplasms (REAL), which proposed that disease entities
      should be defined by a constellation of pathobiological and clinical features.

PMID- 10903056
TI  - Experimental carinal replacement with an Y-shaped collagen-conjugated prosthesis.
AB  - BACKGROUND: A new prosthesis was designed for reconstruction of the bifurcation
      of the trachea and used for experimental carinal replacement in dogs. METHODS:
      The main Frame of the new prosthesis consists of Y-shaped Marlex mesh tube
      reinforced with polypropylene spirals. It is coated with collagen extracted from
      porcine skin to provide biocompatibility and airtightness. Carinal replacement
      with omentopexy was performed in 17 dogs. RESULTS: Seven dogs survived the
      postoperative period, and 10 dogs died within 11 days after the operation. The
      main causes of early postoperative death were fistula and air leakage from the
      prosthesis. Causes of late postoperative death were obstruction of the main
      bronchus (two) and lung abscess (one). The four long-term survivors had no
      stenosis or dehiscence until they were sacrificed 15 months after the operation.
      Histological examination of these dogs revealed that the luminal surface was
      covered either with ciliated columnar epithelium or non-ciliated squamous
      epithelium. CONCLUSIONS: The study results suggest the possibility of successful
      prosthetic carinal reconstruction with epithelial regrowth using this Y-shaped
      prosthesis.

PMID- 10903057
TI  - Results of combined resection of adjacent organs in lung cancer.
AB  - BACKGROUND: Indications for surgical treatment in advanced lung cancer still
      remain to be established. METHODS: The outcomes of combined resection of adjacent
      organs in lung cancer were assessed in terms of complications and the
      invasiveness of surgery, using intraoperative blood loss and operation time as
      indices. RESULTS: In 68 patients undergoing combined resection between 1980 and
      1997, the 5-year-survival rates and the incidence of complications and hospital
      deaths were 24.5%, 52.9%,and 10.3%, respectively. The mean blood loss and
      operation time were 1,200 ml and 396 minutes. The rares of complications and
      hospital deaths were significantly higher in the group with 1,000 ml or more
      blood loss, and in the group with 360 minutes or longer operation time.
      CONCLUSIONS: In terms of the survival rate, invasiveness of surgery, and
      complications, the pleura and pericardium were the best indications for combined
      surgery. For the thoracic wall, blood loss was greater and the rates of
      complications and hospital deaths tended to be higher among T3 cases. Both blood
      loss and operation time tended to be greater in T4 cases. Indications for surgery
      need to be carefully determined with respect to curability.

PMID- 10903058
TI  - Prospective evaluation of 3 risk stratification scores in cardiac surgery.
AB  - BACKGROUND: The aim of the study was to evaluate 3 different risk stratification
      scores in cardiac surgery, based on the hospital results of 1,299 patients.
      METHODS: From June 1995 to December 1997, all patients (n = 1,299) undergoing
      coronary artery bypass grafting (CABG) and/or heart valve surgery were
      prospectively enrolled. The postoperative in-hospital outcome (mortality,
      morbidity and length of hospital stay) was analysed in relation to three
      different risk stratification scores (Parsonnet, Higgins and French score).
      RESULTS: The results of 1,299 patients (mean age 62.8 +/- 10.2 years) were
      analysed. 10 patients died, accounting for a total mortality of 0.8%. 13 patients
      (1%) underwent cardiopulmonary resuscitation. In 25 patients (1.9%),
      perioperative myocardial infarction occurred. Performance of the 3 systems was
      assessed by evaluating discrimination with receiver operating characteristic
      (ROC) curves. The area under the ROC curve was 0.761 for Parsonnet, 0.786 for
      Higgins and 0.798 for French score. The French and the Higgins score showed an
      increase of in-hospital mortality, morbidity and length of stay in relation to
      increasing risk classes. CONCLUSION: For objective evaluation of the outcome in
      cardiac surgery, case-mix severity needs to be considered, which is reflected by
      preoperative risk stratification scores. In our study, all the 3 scores showed a
      high discrimination and are appropriate tools to assess mortality in cardiac
      surgery. Especially the French and the Higgins score (restricted to 5 groups),
      due to their simplicity, were useful to predict postoperative outcome in clinical
      routine.

PMID- 10903059
TI  - Troponin-T in patients with unstable and stable angina pectoris undergoing
      coronary bypass surgery.
AB  - BACKGROUND: Troponin-T is a sensitive indicator of minor myocardial damage during
      coronary bypass surgery. METHODS: Troponin-T levels were assessed before and
      repeatedly for 64 hours after coronary bypass surgery in 100 patients with
      unstable and 100 with stable angina pectoris. RESULTS: Postoperative troponin-T
      levels rose significantly within 6 hours followed by a decline until 64 hours. In
      unstable patients who had pain within two days and an acute myocardial infarction
      within two weeks before the operation (Braunwald class IIIC), Troponin-T rose to
      high levels that persisted for 64 h. Sixty-seven percent of these patients had an
      elevated troponin-T >0.10 microg/l already before the operation and a
      perioperative myocardial infarction was recorded in 27%. In contrast,
      postoperative troponin-T levels in remaining patients classified as unstable were
      similar to those in patients with stable angina. Elective operations in the
      control group were performed with a low risk of adverse postoperative events.
      CONCLUSIONS: Patients with Braunwald class IIIC unstable angina suffered to a
      great extent myocardial cell damage following coronary bypass surgery.

PMID- 10903060
TI  - Sepsis and catecholamine support are the major risk factors for critical illness
      polyneuropathy after open heart surgery'.
AB  - BACKGROUND: Critical illness polyneuropathy (CIP) remains a problem after open
      heart surgery. Recently, we reported about a retrospectively performed study
      pointing out that sepsis, the application of higher amounts of catecholamines and
      intervention such as chronic venovenous hemodiafiltration may be involved in the
      onset of CIP. A prospectively performed study is presented in order to evaluate
      the significance of risk factors initially after open heart surgery. METHODS:
      From June 1997 until September 1998, patients undergoing open heart surgery and
      being ventilated beyond 3 days were prospectively enrolled in the study and
      underwent a standard protocol of electromyographic investigation in order to
      determine CIP. Several items were recorded: amount of catecholamines, serum
      levels of urea, creatinine, albumin, and glucose. The duration of sepsis and
      chronic venovenous hemodiafiltration were reevaluated. Additionally the age, the
      left ventricular end-diastolic pressure prior to the operation, the time of ICU
      stay and the time of ventilatory support were compared. RESULTS: Within the
      observation period, 37 adult patients could be enrolled in the study, whereas 12
      patients did develop CIP and 7 patients did not. Patients developing CIP required
      significantly different amounts of epinephrine (0.17 +/- 0.02 vs. 0.09 +/- 0.01
      mg/kg/day, p < 0.05, t-test) higher amounts of norepinephrine (0.06 +/- 0.02 vs.
      0.02 +/- 0.01 mg/kg/day, p<0.05, t-test), and lesser dosages of dobutamine (2.2
      +/- 0.5 vs. 4.9 +/- 0.7, p<0.05, t-test). After cardiac surgery, the plasma
      levels of urea was initially significantly elevated in patients developing CIP
      (127.4 +/- 10.5 vs 97.3 +/- 18.5, p<0.05, t-test) Patients suffering from CIP
      stayed significantly longer in the ICU (40.3 +/- 11.7 vs. 19.6 +/- 11.3 days, p <
      0.05 t-test) with an extended time of ventilator support. (769.6 +/- 05.0 vs
      295.0 +/- 134.0 hours, p<0.05, t-test). Patients of the CIP group were suffering
      significant longer from sepsis than patients without CIP. CONCLUSIONS: Sepsis and
      catecholamine support and an increased level of urea were associated with the
      development of CIP. The prevention of sepsis and a modulation of the
      catecholamine support in order to improve microcirculatory flow may reduce the
      onset of CIP in patients undergoing open heart surgery.

PMID- 10903061
TI  - Nitric oxide increases leukocyte granule release during simulated extracorporeal
      circulation.
AB  - BACKGROUND: Nitric Oxide (NO) is reported to possess anti-inflammatory
      properties. The aim of this study was to investigate if nitric oxide affects
      leukocyte response during simulated extracorporeal circulation (SECC). METHODS:
      Human blood was circulated for 23 hours through SECC circuit. Control group C (n
      = 5) was ventilated with an oxygen/air mixture, and NO was added in the study
      group (n = 5). Leukocyte response was determined by release of myeloperoxidase
      (MPO) and human neutrophil lipocalin (HNL) and by oxygen free radical production,
      estimated using chemiluminescence. RESULTS: Addition of NO significantly
      increased MPO at 30 minutes and 120 minutes of SECC and HNL at 120 minutes of
      SECC. Oxygen free radical production in whole blood was generally not affected by
      NO. Similarly, no significant differences were observed between the groups with
      regard to the chemiluminescence in isolated granulocytes. CONCLUSIONS: Nitric
      oxide increased release of leukocyte granule derived proteins; MPO and HNL at an
      early stage of simulated extracorporeal circulation. At the same time, nitric
      oxide did not affect the whole blood and leukocyte capacity to produce oxygen
      free radicals.

PMID- 10903062
TI  - Sleeve lobectomy of the middle lobe for hilar lung cancer with accompanying
      cardiomyopathy and actinomycosis.
AB  - The indication for sleeve lobectomy of the middle lobe is limited, because the
      frequency of cancer occupying both the middle lobe and its bifurcation is low and
      the more commonly used middle and lower lobectomy is an alternate procedure.
      However, if a patient has accompanying cardiopulmonary restriction, lung
      preservation is paramount. We present a patient with hilar lung cancer (TisN0M0)
      associated with progressive cardiomyopathy, who underwent sleeve lobectomy of the
      middle lobe; the cancer took a favorable course.

PMID- 10903064
TI  - Two discrete masses of leiomyomatosis in a patient, one extending to the right
      atrium.
AB  - Leiomyomatosis extending to the right side of the heart through the inferior vena
      cava (IVC) is an extremely rare neoplasm. Although it is pathologically
      classified as a benign neoplastic formation, its growth and recurrence rate makes
      its extirpation mandatory. In this case report, we describe a 57-year-old woman
      who presented with leiomyotosis extending from the IVC to the right atrium (RA).
      This patient had presented with uterine leiomyoma three years previously. The
      patient died in the operating theatre from hemostatic problems after surgical
      complications arising from the unexpected presence of a second tumor.

PMID- 10903063
TI  - Successful repair of tracheal defect using gelatin-resorcin-formaldehyde-glue
      reinforced fascia patch.
AB  - We describe the case of a 63-year-old female who underwent repair of a membranous
      tracheal defect. The tracheal perforation occurred after subtotal esophageal
      resection, and was associated with empyema due to esophago-gastric anastomotic
      leakage. We employed a fascia patch reinforced with Gelatin Resorcin-
      Formaldehyde/Glutaraldehyde glue for the repair, as pedicle muscular flaps were
      not available due to thoracotomy and a pericardial patch was inadequate because
      of the empyema. Our method was uncomplicated and provided a satisfactory result.

PMID- 10903065
TI  - Vascular tracheobronchial compression syndromes-- experience in surgical
      treatment and literature review.
AB  - Between January 1988 and December 1997 a total of 22 patients (age: 8 days-46
      years) were operated for vascular airway compression syndromes with respiratory
      insufficiency. Vascular anomalies in tracheal compression were double aortic arch
      in 7 patients, (2 previously operated elsewhere), right aortic arch + left
      ligamentum arteriosum in 1, and pulmonary artery sling in 3. Three of these
      patients had secondary long-segment tracheomalacia. Compression of trachea and a
      main bronchus existed in 2 patients with right aortic arch + left ligamentum.
      Isolated main bronchus obstruction was present in 9 patients (abnormal insertion
      of ligamentum arteriosum in 1, status post (s.p.) previous operation for PDA in
      4, s. p. surgery for coarctation in 1, right aortic arch + left ligamentum
      arteriosum in 2, and right lung aplasia + left ligamentum in 1). 3 of these cases
      had secondary long-segment bronchomalacia. All patients had a complex respiratory
      anamnesis [long-term intubation in 7, s.p. tracheostomy in 2 (over 3 months - 3
      years), and progressive respiratory insufficiency in 13). In tracheal
      compression, surgical correction included transsection of the underlying ring or
      sling components (with additional anterior aortic arch translocation in 5
      patients resection-reimplantation of left pulmonary artery in 3, segmental
      tracheal resection in 1, and external tracheal suspension in 2). In the 2 cases
      with compression of the trachea and a main bronchus, aortic "extension" by a
      prosthetic tube was necessary. In isolated main bronchus obstruction, surgical
      decompression basically consisted of transsection of the ligamentum arteriosum or
      resection of its scarry remnant forming the "corner point" of a compression
      between aorta and pulmonary artery. In 3 patients with secondary long-segment
      malacia, additional external bronchus suspension was performed. Effective
      decompression and re-expansion of the airway segment concerned was achieved, and
      was demonstrated by intraoperative endoscopy in all patients. There were 3
      postoperative deaths (sepsis 2; massive, irreversible edema of the tracheal
      mucosa 1). Of the 19 surviving patients 16 could be extubated between the 1st and
      17th (mean = 7.5) postoperative day. In 1 case the preoperative long-term
      tracheostomy had to be left in place for inoperable additional laryngeal
      stricture. 2 patients had to be reoperated (segmental cervical tracheal resection
      after 5 months for primary long-term intubation-related subglottic stenosis in 1,
      esophageal decompression for residual dysphagia after 57 months related to a
      traction phenomenon at the right descending aorta in the other), both with
      gratifying results. In all other patients clinical, endoscopic, and radiographic
      examinations (follow-up = 2 months - 6 years) demonstrate good results.

PMID- 10903066
TI  - Standards and concepts in valve surgery. A report of the task force of european
      heart institute (EHI) of the european academy of sciences and arts and the
      international society of cardiothoracic surgeons (ISCTS).

PMID- 10903067
TI  - Development of cardiac transplant policy in Germany.

PMID- 10903068
TI  - Transforming growth factor-beta1 and prostate cancer.
AB  - Transforming growth factor-beta1 (TGF-beta1) is an important regulator of the
      normal and malignant prostate. In the non-malignant prostate, TGF-beta1
      stimulates cell differentiation, inhibits epithelial cell proliferation and
      induces epithelial cell death. TGF-beta1 is secreted into semen and here it is an
      important immunosuppressive factor. Prostate cancer cells express high levels of
      TGF-beta1 and it seems to enhance prostate cancer growth and metastasis by
      stimulating angiogenesis and by inhibiting immune responses directed against
      tumour cells. Prostate cancer cells frequently lose their TGF-beta receptors and
      acquire resistance to the anti-proliferative and pro-apoptotic effects of TGF
      beta1. Accordingly, high expression of TGF-beta1 and loss of TGF-beta receptor
      expression have been associated with a particularly bad prognosis in human
      prostate cancer patients. TGF-beta1 also seems to be a mediator of castration
      induced apoptosis in androgen dependent normal and malignant prostate epithelial
      cells. The ability of some prostate tumours to avoid castration-induced apoptosis
      is however not simply due to loss of TGF-beta receptor type I or II expression in
      the tumour cells, but may also be related to an inability of these cells to up
      regulate TGF-beta receptor levels in response to castration or possibly due to
      defects downstream of the receptors. Short-term therapy-induced changes in the
      TGF-beta system in prostate tumours can probably be used to predict the long-term
      response to androgen ablation treatment. Further investigations into the TGF-beta
      system in the prostate are, however, needed to elucidate how alterations in this
      system affect the behaviour of prostate tumours, and if this system can be
      manipulated for therapeutical purposes.

PMID- 10903069
TI  - Prospective registration of all patients in a geographical region with newly
      diagnosed bladder carcinomas during a two-year period.
AB  - OBJECTIVE: To report the age, stage and grade of all patients with newly
      diagnosed bladder carcinoma in a well-defined geographical region and to compare
      this cohort with previous reports which come mainly from large referral centres.
      MATERIAL AND METHODS: All newly diagnosed bladder carcinoma patients (n = 701) in
      Western Sweden were prospectively registered during a 2-year period (1987-88).
      The histopathological material was re-examined by a reference pathologist. All
      the original clinical records were reviewed by one urologist 5-7 years after
      diagnosis. Demographic data, tumor grade, stage, multiplicity, presence of
      carcinoma in situ and lymphatic invasion are presented. RESULTS: The mean age at
      diagnosis was 70.5 years. Grade and stage increase with age. The proportion of
      non-invasive tumors (55%) is higher than in any previous Scandinavian report. The
      age-standardized incidence in bladder carcinoma among men in the largest city
      (Goteborg) is 55% higher than in the rest of the region (p<0.0001). Deviations
      between the primary pathologist and the reviewer with regard to tumor grade were
      particularly seen in tumors of grades I and II. CONCLUSIONS: Differences in mean
      age, stage and grade distribution were found between the present report, which
      included all patients with newly diagnosed bladder carcinoma in a geographical
      area, and other reports, which mainly comprised patients from large treatment
      centres. These differences can probably and mainly be explained by selection
      factors such as various degrees of inclusion of low-grade papillary tumors.

PMID- 10903070
TI  - Intravesical pressure during irrigating fluid absorption in transurethral
      resection of the prostate.
AB  - OBJECTIVE: In order to control fluid absorption, various approaches are used to
      reduce intravesical pressure during transurethral resection of the prostate
      (TURP). With a view to finding a target pressure for such efforts, pressure and
      fluid absorption were compared in a meta-analysis of four previous studies
      comprising three different irrigation techniques. MATERIALS AND METHODS:
      Intravesical pressure was recorded during TURP in which the irrigating fluid was
      evacuated intermittently (n = 48) by a suprapubic tube (n = 23) or a trocar (n =
      30). Fluid absorption was compared with the mean and maximum pressures and the
      duration of excessive pressure (>2 kPa) over 10-min periods. RESULTS: Mean
      bladder pressure during fluid absorption was between 1.0 and 2.5 kPa. The maximum
      pressure during absorption varied greatly during the first 30 min of TURP, but
      thereafter it ranged between 2 and 3 kPa. Only the duration of pressures >2 kPa
      increased with fluid absorption (p < 0.02). The maximum pressures were highest
      with the intermittent technique, while the other indices of intravesical pressure
      showed the highest values when the suprapubic tube was used. The lowest pressures
      usually occurred when the trocar was used, but fluid absorption still occurred,
      as the pressure was much higher during some of these operations. CONCLUSIONS:
      Fluid absorption occurred at moderate intravesical pressures with all three
      irrigation techniques. The best strategy for reducing fluid absorption is to keep
      the pressure below 2 kPa for as long as possible during TURP.

PMID- 10903071
TI  - Management of contralateral adrenal metastasis from renal cell carcinoma:
      possibility of inferior vena cava tumour thrombus.
AB  - OBJECTIVE: The contralateral adrenal gland is a rare metastatic site in renal
      cell carcinoma (RCC). We describe our experiences with this metastasis in a
      cohort of 610 radical nephrectomy patients analysed. To our knowledge this study
      is the first to demonstrate an inferior vena cava tumour thrombus from
      metachronous contralateral adrenal metastasis. PATIENTS AND METHODS: After
      radical nephrectomy for RCC, 610 patients treated at our institution from 1985-99
      were retrospectively investigated for the incidence of contralateral adrenal
      metastasis, additional clinical findings, treatment modalities and survival after
      treatment for contralateral adrenal gland metastasis. RESULTS: The incidence of
      contralateral adrenal metastasis was 1.1% (7/610 patients), while the incidence
      of ipsilateral metastasis was 3.4% (21/610). In 3 of 7 cases the contralateral
      adrenal metastasis occurred simultaneously with primary RCC in the kidney. The
      contralateral adrenal gland was affected by distant tumour spread metachronously
      in 4 of 7 cases (3/4 bilateral adrenal involvement, 1/4 unilateral disease). In 1
      case a metachronous contralateral adrenal metastasis caused vena cava tumour
      thrombus by propagation via the suprarenal venous route. After a mean follow-up
      of 20 months (range 1-54 months), 4 of 6 patients showed no evidence of disease
      after contralateral adrenalectomy. CONCLUSIONS: The probability of contralateral
      adrenal metastasis from RCC is 1.1%. Adrenalectomy in these cases offers a good
      chance of cure. In 71% of cases contralateral adrenal metastasis occurs in
      conjunction with ipsilateral disease, which provides a strong argument for
      routine ipsilateral adrenalectomy during radical nephrectomy. Care must be taken
      in preoperative diagnostics, as metachronous adrenal metastasis is capable of
      causing vena cava tumour thrombus.

PMID- 10903072
TI  - Current management of calculi in horseshoe kidneys.
AB  - OBJECTIVES: To assess treatment options for calculi in horseshoe kidneys and the
      impact of extracorporeal shockwave lithotripsy (ESWL) on the management of renal
      stones. MATERIAL AND METHODS: From June 1971 to January 1998, 52 patients with
      horseshoe kidneys and calculi received treatment at our Urologic Stone Unit.
      There were 40 men (77%) and 12 women (23%). Average patient age was 41 years
      (range: 10-70 years). Clinical onset, treatment received and outcome were
      evaluated retrospectively. A successful outcome was defined as a patient without
      residual calculi or with fragments <0.4 cm in size. RESULTS: Clinical onset was
      mainly low back pain in 37 patients (71%). Eighty-nine stones were treated, i.e.
      an average of 1.7 treatments per patient. Before the ESWL era (May 1987), we
      performed two heminephrectomies, 16 pyelolithotomies, 12 pyelolithotomies
      combined with ureteropyeloplasty and one percutaneous nephrolithotomy. Since the
      advent of ESWL, seven pyelolithotomies and three pyelolithotomies combined with
      ureteropyloplasty have been done. ESWL was used to treat 48 calculi. In three
      cases the patient was placed in the prone position due to difficulties in stone
      focusing. In 37 cases (77%) patients were either rendered stone-free or had
      residual fragments <0.4 cm in size. Urinary diversion for obstruction was carried
      out in two cases (4%). CONCLUSIONS: At present ESWL is the first-choice treatment
      for calculi in horseshoe kidneys. It involves no significant focusing
      difficulties and is associated with a low incidence of obstructive complications.
      Open surgery is indicated in cases of stone-related pyeloureteral stenosis and in
      the presence of calculi >2-2.5 cm in size.

PMID- 10903073
TI  - Clinical assessment after varicocelectomy.
AB  - The present study, conducted in Hong Kong, was designed to evaluate the clinical
      assessment and interobserver variation between doctors with different levels of
      training in the assessment of recurrent varicoceles, and to compare their
      findings with those made by ultrasound. Fifteen patients, previously operated for
      left varicocele testis, were evaluated clinically by four observers. The mean age
      was 12.9 years (range 8-15 years) at surgery. The testicular texture, size and
      flow with and without the Valsalva manoeuvre were determined by colour Doppler
      sonography. The follow-up time was 6-48 months after surgery. The echotexture of
      the testes was normal in all patients. The mean volumes of the left and right
      testes were equal after surgery (left 9.0 ml [range 2.4-15.2 ml and right 8.7 ml
      [range 3.4-15.6 ml]). There was large variation between observers in the
      predictability of both positive and negative clinical findings of varicocele
      testis when compared with ultrasound. Objective assessment in grading varicocele
      testis and testicular volume using ultrasound is required for both clinical
      management and scientific research.

PMID- 10903074
TI  - Transurethral ureterocystostomy.
AB  - Management of distal ureteric obstruction because of impacted stone, malignancy
      or scarred orifice using conventional methods may be cumbersome or may fail.
      Transurethral ureterocystostomy, performed by direct vision using resectoscope
      and Colling's knife in combination with fluoroscopic X-ray control, has solved
      the problem in seven patients with stones, two with prostatic cancer and one with
      scarred orifice. Thus, temporary or permanent transurethral ureterocystostomy can
      be recommended in selected cases of obstruction of the distal ureter by stone,
      malignancy or scar.

PMID- 10903075
TI  - Effects of haemodialysis on pulmonary clearance of Tc-99m diethylene triamine
      pentaacetate (DTPA).
AB  - OBJECTIVES: Hypoxaemia occurring during haemodialysis has long been known.
      Several mechanisms in the pathogenesis have been proposed. The present study was
      conducted to test whether changes in pulmonary alveolar permeability were among
      the operating mechanisms. MATERIALS AND METHODS: Twenty haemodialysis patients
      (12 male, 8 female) were included in the study. The mean age was 49 years (age
      range: 18-85 years). Patients with known pulmonary disease, current smokers and
      those gaining more than 1 kg weight during the interdialytic period were
      excluded. Complete blood count, arterial blood gas analysis, pulmonary function
      tests and Tc-99m diethylene triamine pentaacetate (DTPA) inhalation scintiscan
      were carried out before and after haemodialysis. A bronchial provocation test was
      carried out after each session. A postero-anterior chest radiogram was taken for
      each patient. RESULTS: When the results before and after haemodialysis were
      compared, it was observed that the pH and serum bicarbonate levels, haemoglobin
      and haematocrit values were significantly higher after haemodialysis. However,
      the platelet count was found to be decreased significantly. Bronchial
      hyperreactivity, tested by metacholine, Was positive in 5 of 19 patients (26%).
      No correlation between bronchial hyperreactivity and other factors could be
      identified. No significant difference was observed in pulmonary Tc-99m DTPA
      clearance after haemodialysis. All chest radiograms were interpreted to be within
      normal limits. CONCLUSIONS: Since we observed no hypoxaemia following
      haemodialysis, we cannot comment as to whether the changes in pulmonary clearance
      play a role in the pathogenesis of haemodialysis-associated hypoxaemia. In order
      to reach reliable conclusions, additional studies are needed.

PMID- 10903076
TI  - Stimulation of tumour necrosis factor-alpha production by recombinant human
      erythropoietin may contribute to failure of therapy.
AB  - Although the mechanism of unresponsiveness to recombinant human erythropoietin
      therapy in dialysis patients has been studied extensively in recent years, many
      aspects remain unclear. We previously found that administration of erythropoietin
      induces interleukin-1beta, a cytokine that inhibits erythropoiesis. The present
      study investigated the involvement of tumour necrosis factor-alpha, another
      cytokine which inhibits erythropoiesis. Peripheral blood mononuclear cells were
      obtained from 18 patients on continuous ambulatory peritoneal dialysis, who were
      being treated with erythropoietin for renal anaemia, and were cultured with
      various concentrations of erythropoietin (0, 1, 5, 10, and 50 U/ml). Then the
      tumour necrosis factor-alpha level in the culture supernatant was assayed. The 18
      patients were divided into four groups on the basis of the haematocrit after
      treatment: group A (n = 3), <23.0%; group B (n = 5), 23.0-24.9%; group C (n = 7),
      25.0-26.9%; and group D (n = 3), > or =27.0%. In group A, the tumour necrosis
      factor-alpha level in the culture supernatant was increased by incubation with
      erythropoietin, while it was not increased in other groups. The tumour necrosis
      factor-alpha level was significantly higher in group A than in the other groups
      at erythropoietin concentrations of 5 U/ml. These results suggested that
      induction of tumour necrosis factor-alpha is one of the reasons for
      unresponsiveness to recombinant human erythropoietin.

PMID- 10903077
TI  - Clear cell adenocarcinoma in a female urethral diverticulum.
AB  - The incidence of a neoplasm within the female urethral diverticulum is rare.
      Clear cell adenocarcinoma, which is the most common neoplasm, arises from the
      metaplasia of surface transitional epithelium and the paraurethral ducts. These
      tumors are usually diagnosed at a late stage, which worsens their prognosis. The
      treatment of choice is surgery.

PMID- 10903078
TI  - Giant neobladder calculus.
AB  - An unusual case of a calculus in the ileal neobladder is presented. The size of
      the stone is exceptional in the urologic literature (940 g). Neocystolithotomy
      was performed, with full patient recovery.

PMID- 10903079
TI  - Stage T1 adenocarcinoma of the urinary bladder--complete response after
      transurethral resection and intravesical bacillus Calmette-Guerin.
AB  - OBJECTIVE: To report the results of treatment of adenocarcinoma of the urinary
      bladder with transurethral resection and intravesical bacillus Calmette-Guerin
      (BCG). METHODS: Out of 183 patients in our department treated with BCG between
      1992 and 1996, three patients had adenocarcinoma, stage T1. RESULTS: All three
      patients had normal cystoscopy and negative cytology 53-82 months after the start
      of treatment. CONCLUSIONS: BCG appears to be effective not only in the treatment
      of transitional cell carcinoma, but also in adenocarcinoma of the bladder.

PMID- 10903080
TI  - The role of solid state 13C NMR spectroscopy in studies of the nature of native
      celluloses.
AB  - Published spectroscopic observations pertaining to the crystal structure of
      native celluloses are reviewed for the purpose of defining our current level of
      understanding about crystalline polymorphism in these materials. Emphasis is
      placed on observations from solid state 13C nuclear magnetic resonance (NMR),
      which first led to the postulate that most native, semicrystalline celluloses are
      composites of two crystalline allomorphs, labeled Ialpha and Ibeta. Historical
      background is presented, highlighting the structural controversies which mainly
      arose because different native celluloses were used, each one representing a
      different mixture of allomorphs. Input from Raman, infrared (IR) and electron
      diffraction data is included in the discussion of our current understanding of
      polymorphism in native celluloses. Also noted is the input from more recently
      studied celluloses (e.g., Halocynthia) as well as from newer processes that
      convert the Ialpha to the Ibeta form. On the basis of Raman and IR observations,
      it is argued that the Ialpha and Ibeta allomorphs differ in hydrogen bonding
      patterns only and that backbone conformations are nearly identical. Also, the
      point is made that the absence of correlation field splittings in the Raman
      spectra calls into question (although it does not disprove) whether the normal
      two-chain-per-unit-cell, monoclinic Ibeta allomorph really possesses two
      equivalent chains. Considerable discussion is devoted to the allomorphic
      composition of cellulose crystallites in higher plants. Published methods of NMR
      lineshape analysis for the higher plant celluloses are reviewed and critiqued,
      both from the point of view of lineshape theory and from the point of view of
      self-consistency of inferences that are based on lineshape analyses for different
      carbons (particularly C1 and C4). It is concluded that higher plant celluloses
      most likely possess a minor amount of the Ialpha allomorph where the Ialpha/Ibeta
      ratio is probably less than 0.25.

PMID- 10903081
TI  - Estimation of the lateral dimensions of cellulose crystallites using 13C NMR
      signal strengths.
AB  - Differences in proton rotating-frame spin relaxation rates were exploited to edit
      the 13C NMR spectra of solid lignocellulosics, separating signals assigned to
      cellulose crystallites from signals assigned to amorphous material. Clusters of
      signals at 89 and 85 ppm were assigned to C-4 in the interiors and on the
      surfaces of cellulose crystallites, respectively. Relative signal areas were used
      to estimate the weight-averaged lateral dimensions of crystallites, using a model
      in which crystallites have approximately square cross sections. The same 10
      samples were also characterized by wide-angle X-ray scattering (WAXS). There was
      a strong correlation (r2 = 0.988) between the two sets of lateral dimensions, but
      those estimated by WAXS were typically 10% lower than those estimated by NMR. The
      deviations were attributed to differences in molecular conformations between
      interior and surface chains, causing broadening of the WAXS peaks. In the case of
      an eleventh sample containing well-ordered xylan, the NMR and WAXS methods were
      in good agreement only after exclusion of a xylan signal at 82.6 ppm from the NMR
      data.

PMID- 10903082
TI  - CP/MAS 13C-NMR spectroscopy applied to structure and interaction studies on
      cellulose I.
AB  - Solid-state Cross-Polarization Magic Angle Spinning Carbon-13 Nuclear Magnetic
      Resonance (CP/MAS 13C-NMR) has been used to investigate the structure and
      interactions of cellulose I. The use of spectral fitting for the extraction of
      information from CP/MAS 13C-NMR spectra is reviewed and results obtained are
      discussed. Examples are shown where the method has been used to monitor the
      structural changes occurring in wood cellulose during kraft pulping. The effects
      observed on the cellulose and hemicelluloses are further investigated using a
      model system. Assignments of signal intensities originating from xylan-cellulose
      interactions are made.

PMID- 10903083
TI  - Solid-state spectroscopic analysis of lignins from several Austral hardwoods.
AB  - In order to gain information about lignin molecular characteristics with a direct
      bearing on the remarkable susceptibility of some Austral hardwoods to biological
      delignification, milled-wood lignins were isolated and analyzed by spectroscopic
      techniques in the solid state. Cross polarization and magic-angle spinning 13C
      nuclear magnetic resonance (13C CPMAS NMR) and Fourier-transform infrared (FTIR)
      spectra of the lignin preparations were obtained. The most diagnostic peaks were
      assigned and quantified as percentages of the total spectral area, and the
      differences observed discussed in terms of lignin composition. The spectral
      patterns obtained revealed that the woods from Gevuina avellana, Eucryphia
      cordifolia and Nothofagus dombeyii have lignin with high syringyl/guaiacyl ratio,
      as evidenced by relative areas of 13C NMR signals at 153 and 148 ppm, and FTIR
      bands at 1,335 and 1,275 cm-1. The presence of syringyl-rich lignins,
      characterized by lower redox potential and condensation degree than guaiacyl-rich
      lignins, could be a structural factor contributing to the ease of extensive
      delignification of these woods by white-rot fungi.

PMID- 10903084
TI  - Proton spin-lattice relaxation time measurements of solid wood and its
      constituents as a function of pH: part II.
AB  - The proton spin-lattice relaxation times (T1H) for isolated cuoxam lignin and
      fully bleached cellulose were measured as a function of pH in the solid-state.
      These experiments provided the opportunity to examine for possible macromolecular
      connectivities that may be present between lignin and carbohydrates within
      softwood. These studies have shown that the molecular mobilities of the isolated
      polymeric constituents of wood are affected by the ionization of their functional
      groups at different pHs. The shapes of the plots of T1H as a function of pH for
      the two isolated polymers were dramatically different, while those for softwood
      were similar. This fact provides evidence supporting the notion that in wood,
      lignin and carbohydrates are intimately associated with each other.

PMID- 10903085
TI  - Very high-resolution 1H MAS NMR of a natural polymeric material.
AB  - The use of ultrafast magic angle spinning (> 30 kHz) in tandem with delayed echo
      acquisition is shown to yield very high-resolution lH MAS NMR spectra of complex
      natural organic materials. For the first time, very high-resolution 1H MAS NMR
      spectra are reported for cork and wood components, two natural materials with
      great economic importance. The effect of the spinning rate on the 1H NMR spectra
      was evaluated with single-pulse acquisition and delayed-echo acquisition. The
      delayed-echo acquisition spectra presented linewidths as sharp as 67 and 25 Hz.
      The narrow peaks, characterised by proton spin-spin and spin-lattice relaxation,
      were assigned to the isotropic chemical shifts and the general spectral features
      were shown to correlate with the sample chemical structure. The tentative
      assignments of cork 1H MAS NMR signals were presented.

PMID- 10903086
TI  - 11B magnetic resonance imaging and MAS spectroscopy of trimethylborate-treated
      radiata pine wood.
AB  - Boron-11 nuclear magnetic resonance imaging and spectroscopy have been used to
      characterise the nature and distribution of boron compounds after preservative
      treatment of radiata pine wood with trimethylborate (TMB). One day after
      treatment, 11B magnetic resonance imaging microscopy showed significant
      differences in the morphological distribution of boron species, with there
      apparently being no treatment penetration of the latewood. 11B MAS NMR
      spectroscopy of freshly preservative-treated radiata pine wood, which had been
      separated into latewood and earlywood, showed the only boron species present in
      the latewood to be boric acid while in the earlywood both TMB and boric acid were
      initially present. Due to quadrupolar broadening and a short T2 value, the boric
      acid signal relaxed too quickly to be observable and this caused the apparent
      lack of 11B in the image when only boric acid was present. TMB undergoes
      hydrolysis to form boric acid and in radiata pine latewood, this hydrolysis
      reaction is rapid.

PMID- 10903087
TI  - Binding of dialkylated disulfonated diphenyl oxide surfactant onto alumina in the
      aqueous phase
AB  - Adsorption of a gemini surfactant that has two monomers and a spacer in a
      molecule (dialkylated disulfonated diphenyl oxide with alkyl chain lengths of
      twelve, DADS-C12) onto positively-charged aluminum oxide in water was studied and
      compared with a single-monomer anionic surfactant (sodium dodecylbenzene
      sulfonate, SDDBS). More mass of the gemini surfactant was adsorbed than the
      conventional single-monomer SDDBS. Fewer moles of the first were bound to the
      substrate than the second indicating that larger molecular structure of the
      gemini surfactant does not hinder the sorption. Both surfactants followed similar
      sorption mechanisms, however, stronger hydrophobic interactions were shown in the
      bilayer formation of the adsorbed gemini surfactant.

PMID- 10903088
TI  - Contamination of human milk in Middle Hesse, Germany--a cross-sectional study on
      the changing levels of chlorinated pesticides, PCB congeners and recent levels of
      nitro musks.
AB  - Human milk samples from women in Middle Hesse, Germany were chemically analyzed
      for contamination levels of alpha-, beta- and gamma-HCH, HCB, p,p'-DDE and p,p'
      DDT as well as the PCB-congeners no. 28, 31, 49, 52, 101, 118, 138, 153, 156, 170
      and 180. Changes in concentrations of these compounds in human milk over an
      extended time period were studied by comparing samples from 1984/85, 1990/91 and
      1995. In addition, concentrations of the nitro-aromatic compounds musk xylene and
      musk ketone were determined in the 1995 samples. The study showed statistically
      highly significant (p<0.001) reductions in levels of beta- and gamma-HCH, HCB,
      p,p'-DDE and p,p'-DDT, in human milk from 1995 compared to samples from 1984/85.
      A weakly significant reduction (p<0.05) of alpha-HCH was also observed. For low
      chlorinated PCB congeners, on the other hand, a highly significant increase of
      PCB no. 28 was detected and concentrations of congeners no. 31, 49 and 52
      remained unchanged. Concentrations of the high-chlorinated congeners no. 101,
      138, 153 and 180 dropped (highly significant). A highly significant reduction of
      PCB no. 118 and 156 occurred between 1990/91 and 1995, but a highly significant
      increase was found for no. 170. Lower levels of hydrocarbon contamination of
      human milk samples from 1995 than were found in samples from 1984/85 and 1990/91
      can be seen to result partially from voluntary reductions, but primarily reflect
      restrictive environmental legislation in the Federal Republic of Germany. Mean
      concentrations of musk xylene and musk ketone in samples from 1995 were 41
      microg/kg and 10 microg/kg milk fat, respectively.

PMID- 10903089
TI  - Occurrence of organochlorine insecticides, PCBs and PCB congeners in waters and
      sediments of the Ebro River (Spain)
AB  - Organochlorine insecticides and poychlorinated biphenyls (PCBs) were measured in
      water and sediment samples taken from thirteen sites along the Ebro River
      (Spain), the most agricultural and industrial basin in the North of the Iberian
      Peninsula. Concentrations of 10 insecticides, PCBs and 13 PCB congeners were
      determined: grouping all chemicals by structural affinity, these can be arranged
      in descending order as follow: PCBs > total DDT > total cyclodiene insecticides >
      total HCH. Higher levels of organochlorine pollutants were detected in sediments
      from the middle and lower parts of the stream where are located the main
      important inputs in Ebro River.

PMID- 10903090
TI  - Differentiating with fluorescence spectroscopy the sources of dissolved organic
      matter in soils subjected to drying
AB  - The relative fluorescence, normalised on dissolved organic carbon (DOC), and a
      humification index, based on the location of the fluorescence emission spectra,
      were used to investigate the possible sources of the increase in dissolved
      organic matter (DOM) when a soil is dried. From these 2 parameters it could be
      seen that air drying resulted in a minor increase of more humified material in
      DOM while the effect of oven drying was mainly due to cell lysis.

PMID- 10903092
TI  - Ecotoxicological testing with new kinetic Photorhabdus luminescens growth and
      luminescence inhibition assays in microtitration scale
AB  - Miniaturized luminescence and growth inhibition assays in microtitration plates
      with the terrestric enthomopathogenic nematode symbiont Photorhabdus luminescens
      (DSMZ 3368T) are presented and compared with standardized tests with Vibrio
      fischeri (DSMZ 7151/NRRLB-11177) and Pseudomonas putida (DSMZ 50026).
      Toxicological parameters (EC and G values) of selected reference toxicants (e.g.
      heavy metals and environmental samples) were obtained at different temperatures
      and without sodium chloride supplementation. Kinetic data recordings were
      compared with results of a cuvette test protocol using integral and endpoint
      calculation. Growth inhibition experiments with reference samples reveal similar
      or higher sensitivities as for the Vibrio or Pseudomonas spp. The luminescence
      inhibition assay shows reduced sensitivities to most of the reference samples
      compared with the V. fischeri standard assay. But G values obtained with other
      standardized aquatic assay systems with daphnids, algae and growth inhibition
      assays with V. fischeri and Ps. putida correspond more closely to data observed
      with Ph. luminescens. The test procedures are easily to perform and to evaluate
      and seem to be reliable alternatives to the established protocols at low
      osmolarities. The sample specifity of the toxic responses of the marine and the
      terrestric strain recommends to employ both assays to determine the toxic
      potential of environmental samples. This will support to reduce false positive
      results in future investigations.

PMID- 10903091
TI  - Uptake of weakly hydrophobic nitroaromatics from water by semipermeable membrane
      devices (SPMDs) and by goldfish (Carassius auratus).
AB  - Semipermeable membrane devices (SPMDs) filled with triolein, and goldfish
      (Carassius auratus) were simultaneously exposed to nine weakly hydrophobic
      nitroaromatics in a laboratory continuous-flow experiment. The results showed
      that the device concentrated the compounds in most cases to a larger extent than
      fish and that the overall uptake rate constants (Kmu) and average pollutant
      sampling rates (R(S)) were similar. We conclude that the SPMDs may be used to
      determine the levels of weakly hydrophobic nitroaromatics in water. It is
      obvious, however, that more researches at laboratory in order to establish
      kinetic database for a wide spectrum of compounds varying in lipophilicity and
      other properties are needed to elucidate various theoretical and practical
      aspects of the use of membranes in the environmental research and for related
      practical applications.

PMID- 10903093
TI  - Agonistic and antagonistic toxic effects observed with miniaturized growth and
      luminescence inhibition assays.
AB  - Kinetic data recordings with miniaturized growth and luminescence inhibition
      assays with prokaryotes (Pseudomonas putida and Vibrio fischeri) reveal typical
      sample and species specific growth and light emission patterns respectively.
      Growth inhibiting influences, based on toxicokinetic and toxicodynamic sample
      specificities appeared in each growth phase. Agonistic and antagonistic effects
      of combinations of heavy metals like Cd2+, Hg2+ and Pb2+ and other compounds were
      easily recognized after accurate curve discussions. Some of the influences that
      made it more difficult to evaluate toxicological results only by restriction on
      EC values (effective concentrations) were investigated. The findings may lead to
      a more comprehensive interpretation of toxicological data and a presumption on
      the composition of complex samples in terms of screening investigations.
      Therefore, the conclusions demonstrate the possibilities and limits of kinetic
      data recordings in chronic and acute toxicity testing.

PMID- 10903094
TI  - PCDD/Fs in textiles--part II: transfer from clothing to human skin.
AB  - The transfer of PCDD/Fs from contaminated textiles to the outermost layers of the
      skin (stratum corneum) of human volunteers was measured. The experiments were
      conducted with cotton T-shirts containing high levels of hepta- and
      octachlorinated dibenzo-p-dioxins and dibenzofurans. The results indicated that
      there is little spatial variability in the transfer from the T-shirt to the skin
      surface (< factor2) and also little variability among individuals (< factor 3).
      The percent transfer from different cotton textiles (sigma PCDD/F: 1,900 pg/g -
      281,000 pg/g) to the stratum corneum was found to be similar. The transfer from a
      white, unbleached polyester material was more than an order of magnitude lower,
      indicating that the PCDD/Fs were more tightly bound to the polyester than to the
      cotton. It was shown that the PCDD/Fs penetrate into deeper layers of the stratum
      corneum during an 8 hour exposure period. However, systemic exposure and a
      significant contribution of this pathway to the PCDD/F body burden is only
      possible if the compounds are able to overcome the penetration barrier posed by
      the viable epidermis.

PMID- 10903095
TI  - Dioxin like compounds from municipal waste incinerator emissions: assessment of
      the presence of polychlorinated naphthalenes.
AB  - Polychloronaphthalenes (PCN) were identified and quantified in emission samples
      collected from five different municipal waste incinerators (MWI).
      Polychlorodibenzo-p-dioxins (PCDD) and polychlorodibenzofurans (PCDF) were also
      determined to find a possible relationship between these classes of
      organochlorinated compounds. The analyses of PCDD/PCDF and PCN were carried out
      by high resolution gas chromatography coupled with high resolution mass
      spectrometry using a positive electron ionization source and operating in the
      selected ion monitoring analyzer mode (HRGC-HRMS/EI(+)-SIM). The total levels of
      PCN varied from 1.08 up to 21.36 ng/Nm3 (mono- to octachlorinated) and 0.33 to
      5.72 ng/Nm3 (tetra- to octachlorinated), whereas the levels of PCDD/PCDF ranged
      between 1.14 and 276.26 ng/Nm3 (0.01 and 5 ng I-TEQ/Nm3), depending on the type
      of the MWI. These findings do not corroborate a PCN and PCDD/PCDF correlation.

PMID- 10903096
TI  - Modelling agrochemical dissipation in surface microlayers following aerial
      deposition
AB  - Conventional chemical fate models which treat the water compartment as being well
      mixed may not adequately describe the fate of chemicals deposited onto lakes and
      ponds from aerial applications or spray drift. The Quantitative Water Air
      Sediment Film Interaction (QWASFI) model is developed here to predict
      agrochemical dissipation in surface microlayers or films following aerial
      deposition on to natural waters. The model was applied to four pesticides:
      bromoxynil octanoate, cypermethrin, deltamethrin and fenitrothion, from five
      previously published studies. QWASFI provided a more accurate description of
      processes, and improved quantification of concentrations than a model which does
      not address the effects of the film compartment.

PMID- 10903097
TI  - Behaviour of EDTA in marine microcosms
AB  - Laboratory-scale microcosm tests were carried out in sea water with and without
      sediment to investigate the importance of ultraviolet (UV) light and microbes in
      the temperature-dependent degradation of metal complexes of
      ethylenediaminetetraacetic acid (EDTA). After 17 weeks, 44% and 48% of the
      original EDTA (initial concentration 385 microg/L) were converted at 10 degrees C
      and 22 degrees C, respectively. The degradation was more influenced by UV light
      than by sediment microbes, although the latter were very important. At both
      temperatures, absorption of EDTA to the sediment phase reached a maximum in the
      initial stage of the experiments (<4 weeks): at 10 degrees C about 4% and at 22
      degrees C about 7% of the original EDTA.

PMID- 10903098
TI  - Glutathione as a matrix for the synthesis of CdS nanocrystallites
AB  - GSH-capped CdS nanocrystallites were synthesized by reacting Cd(II)-GSH with
      aqueous sodium sulfide using specific initial sulfide/Cd(II) ratios.
      Spectroscopic analyses of fractions obtained from a size exclusion column showed
      varying absorption spectra indicating a significant dispersion in size
      distribution of nanocrystallites at lower sulfide/Cd(II) ratios. However, size
      distribution of the nanocrystallites was narrower at initial sulfide/Cd(II)
      ratios that exceeded 1.0. An ethanol precipitation procedure was used to remove
      free Cd(II)-GSH complexes and selectively isolate GSH-capped nanocrystallites in
      a very narrow size range. Size exclusion chromatography indicated similar
      chemical compositions and overlapping spectral profiles of ethanol-precipitated
      samples suggesting apparent uniformity in both the size and the cap content. All
      of the GSH-capped CdS nanocrystallites with varying cap contents degraded p
      nitrophenol upon irradiation at 366 nm. However, photocatalytic degradation of p
      nitrophenol was significantly higher in samples with higher sulfide/Cd ratio and
      less capping material. The addition of H2O2 enhanced levels of photo-oxidation of
      p-nitrophenol.

PMID- 10903099
TI  - Methane consumption by soils of dryland rice agriculture: influence of varieties
      and N-fertilization
AB  - Growth of three rice varieties (Heera, Dhala Heera and Narendra-118) and their
      relationship with methane consumption was investigated under rainfed (dryland)
      condition. Overall methane flux rates ranged between -0.58 to 1.25 mg m(-2) h(-1)
      across varieties, treatments, and dates of measurements. Except for two days when
      soil was saturated, the soil consumed 0.05-0.58 mg CH4 m(-2) h(-1); these rates
      were inversely related with soil moisture. N-fertilization reduced consumption
      rates. Although all plant growth parameters, except for number of tillers,
      exhibited relationship with methane consumption in control plots, only root
      porosity did so in fertilized plots. Combinations of plant growth characteristics
      explained 74-92% variability in seasonal CH4 consumption in unfertilized plots.
      It was concluded that methane consumption by dryland soils was influenced by rice
      variety, soil moisture and nitrogen fertilization.

PMID- 10903100
TI  - Estimating the pKa of phenols, carboxylic acids and alcohols from semi-empirical
      quantum chemical methods
AB  - Quantitative structure property relationships (QSPR) for the pKa of phenols,
      carboxylic acids and alcohols were developed from descriptors derived from semi
      empirical molecular orbital theory quantum chemical calculations. A training set
      of compounds were used to refine the models and a validation set of appropriate
      chemicals were chosen to test the models. Correlation coefficients for the
      estimated versus observed pKa values were 0.96 for phenols, 0.84 for non-aromatic
      carboxylic acids, 0.89 for benzoic acids and 0.89 for alcohols. The results
      obtained by the quantum chemical method are compared to results obtained from
      linear free energy relationships (LFER) and the merits of each approach are
      discussed.

PMID- 10903101
TI  - A review of the role of plastics in energy recovery
AB  - This report reviews the major scientific investigations that have been reported
      world wide over the last ten years on the effect of plastics on the process and
      emission performance of energy from waste (EFW) facilities. Concentrations of
      contaminants in air emissions and other process residues measured during tests
      with added plastics are compared with concentrations during normal operations and
      with the stringent emission limits stipulated in municipal waste combustor
      standards and guidelines in Canada, the United States and the European Union. The
      emission limits in these standards and guidelines are based on the use of the
      best technology available (Maximum Achievable Control Technology (MACT) standards
      in North America and Best Available Technology (BAT) standards in Europe) and are
      amongst the most stringent in the world.

PMID- 10903102
TI  - C3-C14-alkyl nitrates in remote South Atlantic air
AB  - Alkyl nitrates with chain lengths up to fourteen carbons have been detected in
      the remote troposphere of the South Atlantic Ocean. The concentrations of
      numerous iso- and n-alkyl nitrates in the range of C3-C12 have been measured.
      Tenax-GC analysis was applied to determine short chain alkyl nitrates (< C6),
      while the novel detection of long chain iso- and n-alkyl nitrates was achieved
      with a high volume sampling technique using silica gel. C3-C12-alkyl nitrates
      show the lowest concentrations in the trade wind region (3.5 pptv). Higher
      concentrations in the west wind belt (11.1 pptv) reveal the influence of the
      South American continent as the source for the alkyl nitrates after long range
      transport. The concentrations of alkyl nitrates increase in proximity to South
      America. Measurements of long chain alkyl nitrates in rural air near the city of
      Ulm (Germany) are given for comparison. In addition, pattern analysis of long
      chain alkyl nitrates reveal this complex mixture of new compounds to be useful as
      trace indicators to distinguish continental and marine air masses. Despite the
      lower photochemical formation yields of primary n-alkyl nitrates compared to
      secondary n-alkyl nitrates, the primary n-alkyl nitrates are relatively increased
      in marine air. The reason for this finding cannot be explained so far, but the
      correlation of secondary/primary n-alkyl nitrates shows a significant
      differentiation of air samples with continental or marine character.

PMID- 10903103
TI  - Beta-cyclodextrin(beta-CD) influence on the biotoxicities of substituted benzene
      compounds and pesticide intermediates.
AB  - The acute toxicities of 19 substituted benzene compounds and intermediates of
      pesticides to Photobacterium phosphoreum in beta-CD aqueous solution (5 g/L) were
      studied and compared with those in water through luminescent bacteria toxicity
      test, and 15min-EC50 values were obtained. The presence of beta-CD significantly
      reduce biotoxicities of the low-polarity compounds, while for the higher-polarity
      compounds, such effect was slight. The differences of biotoxicities were
      correlated with Log10Kow (octanol/water partition coefficients). A significant
      linear relationship was obtained with some abnormal data picked out. Some
      explanations concerning molecular structure of chemicals as well as beta-CD were
      given for the relationship.

PMID- 10903104
TI  - Adaptation of the CAS test system and synthetic sewage for biological nutrient
      removal. Part I: development of a new synthetic sewage.
AB  - A new synthetic medium has been developed for routine use in laboratory-scale
      sewage treatment simulation and biodegradation tests, such as OECD guideline 302A
      & 303A or ISO method 11733. The new medium, Syntho, was designed to meet the
      following objectives: 1) to be more representative of real sewage than the
      existing standard OECD synthetic sewage, 2) the COD:N:P ratio and mineral
      composition must allow a good degree of biological nutrient (N, P) removal, and
      3) the medium should result in stable unit operation, including good sludge
      settling and minimal need for control actions. The IAWQ Activated Sludge Model
      No. 2 (ASM2,) was used to help design the medium and predict reactor performance
      for different possible media compositions. The results obtained with Syntho
      indicate that Continuous Activated Sludge (CAS) units with or without nutrient
      removal can be operated routinely on this feed. The new medium was also
      characterized by means of a respiration test. The different influent fractions
      applied in the model were validated, and a respiration profile indicated that
      Syntho is a close approximation of real sewage.

PMID- 10903106
TI  - Modifications of the sex pheromonal communication of trichogramma brassicae by a
      sublethal dose of deltamethrin
AB  - Pyrethroid insecticides, by their intensive use and their persistence that can
      exceed 3 months, largely contribute to the environmental pollution. In this work,
      we determined the effects of a very low dose of deltamethrin on the sex
      pheromonal communication of Trichogramma brassicae. The dose used was a dose that
      would theoretically kill one insect over 1000 (an LD 0.1). We found that this
      dose slightly but very significantly increased the arrestment behavior of treated
      males responding to the female pheromone. On the other hand when females were
      exposed to the same dose of insecticide, the response of males to their pheromone
      was very significantly decreased. In Trichogramma, like in other insects, sex
      pheromonal communication probably involves nervous transmissions both for the
      reception and the emission of the pheromone. Then, the sublethal effects of
      deltamethrin, observed in this work, are certainly due to multiple actions of
      this insecticide on nervous transmissions. Trichogramma is a beneficial insect
      that contributes to the control of pest populations of moths. Actions of this
      insecticide at a dose that can correspond to environmental pollution could be a
      real threat to the equilibrium of these populations.

PMID- 10903105
TI  - Adaptation of the CAS test system and synthetic sewage for biological nutrient
      removal. Part II: design and validation of test units.
AB  - A global increase in biological nutrient removal (BNR) applications in wastewater
      treatment and concern for potential effects of anthropogenic substances on BNR
      processes resulted in the adaptation of the Continuous Activated Sludge (CAS)
      laboratory test system (cf. guideline OECD 303A or ISO 11733). In this paper two
      novel systems are compared to the standard CAS unit: the Behrotest KLD4 and a
      University of Cape Town system (CAS-UCT). Both are 'single sludge' systems with
      an anoxic/aerobic and an anaerobic/anoxic/aerobic configuration, respectively.
      They both can simulate the essential processes of full-scale BNR installations.
      The units where fed with a specially designed synthetic sewage, Syntho (cf. Part
      I of this study), or its precursor BSR3 medium. The performance of the two new
      units was benchmarked against the standard CAS system in terms of
      carbon/nitrogen/phosphorus (C/N/P) removal, as well as primary biodegradation of
      the surfactants linear alkylbenzene sulfonate (LAS) and glucose amide (GA). Both
      systems allow to easily achieve stable excess N- and P-removal. Experimental
      C/N/P removal data compared closely with simulations obtained with the IAWQ
      Activated Sludge Model No. 2 (ASM2), and with full scale BNR plants with a
      similar configuration. In both units the effluent concentrations of the
      surfactants tested were significantly reduced in comparison to the standard CAS
      system (up to 50% less). No adverse effects on BNR were noted for the test
      surfactants dosed at 400 microg/l together with an overall surfactant background
      concentration in the feed of ca. 20 mg/l. The proposed systems hold potential to
      complement the standard CAS system for situations where advanced sewage treatment
      plants with BNR need to be simulated in the laboratory with minimum effort.

PMID- 10903107
TI  - Light induced transformation of tribenuron-methyl
AB  - To study the photostability of sulfonylurea herbicide tribenuron-methyl (methyl 2
      [[[[ N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl) methylamino]
      carbonyl]amino]sulfonyl]benzoate), in the field, model experiments with organic
      solvents were performed. Irradiation of tribenuron-methyl in methanol,
      isopropanol and cyclohexane yielded 4-methoxy-6-methyl-2-aminomethyl-1,3,5
      triazine; methyl-2-(aminosulfonyl) benzoate; N-(4-methoxy-6-methyl-1,3,5-triazin
      2-yl)-N-methyl urea; N-(2-carbomethoxy phenyl)-N-(4-methoxy-6-methyl-1,3,5
      triazin-2-yl)-N'-methyl urea; 2-(aminosulfonyl) benzoic acid, N-methyl saccharin
      and saccharin in considerable amounts. The rate of degradation in different
      solvents followed first-order kinetics with a statistically significant
      correlation coefficient.

PMID- 10903108
TI  - The influence of quinones and phenols on the triple NAD(H)-dependent enzyme
      systems
AB  - Kinetics of the triple bioluminescent enzyme system: alcohol dehydrogenase-
      NADH:FMN-oxidoreductase--luciferase in the presence of quinones and phenols has
      been studied. The correspondence between the bioluminescent kinetic parameters,
      redox potentials and concentrations of the quinones and phenols has been
      estimated. The substances have been shown to change bioluminescent kinetics
      through moving off the NAD+/NADH balance in the enzyme processes. This system is
      proposed to be used as enzymatic biotest in ecological monitoring.

PMID- 10903109
TI  - Improvements to the UK PCDD/F and PCB atmospheric emission inventory following an
      emissions measurement programme
AB  - PCDD/F data are presented from 75 samples of primary emissions sampled between
      1995-97 as part of the compliance monitoring survey undertaken by the UK
      Environment Agency. Municipal solid waste (MSW), chemical waste and clinical
      waste incinerators, cement kilns, sinter plants and sewage sludge incinerators
      were the source categories monitored and reported here. Based on this monitoring
      programme, the previous national UK emission estimates by Eduljee and Dyke (1) of
      560-1100 g I-TEQ a(-1) for 1993 have been revised downwards to 220-660 g I-TEQ a(
      1). Despite source reduction measures, MSW incinerators remain a significant
      source of PCDD/Fs to the atmosphere, contributing between 30-50% of the EPCDD/F I
      TEQ emission, rather than the approximately 80% they were estimated to contribute
      in 1993. 2,3,7,8-substituted PCDD/F congener profile data are presented for some
      of the source categories and generally support the view that differences in the
      mixtures ('fingerprints') of PCDD/Fs emitted from different sources are observed.
      New data on the dioxin-like PCB emissions are presented for cement kilns and
      sinter plants. These show that TEQ-rated PCBs can make an important contribution
      to the I-TEQ emitted from certain combustion sources. High concentrations of a
      full range of PCB congeners/homologues have been measured in the atmosphere close
      to sintering strands, although the precise source of PCBs from this process
      remains unclear.

PMID- 10903110
TI  - Determination of group parameters for organically bound chlorine, bromine and
      iodine in precipitation
AB  - The presence of organically bound halogens in precipitation was studied by first
      adsorbing organics on activated carbon and then analysing the chloride, bromide
      and iodide formed during combustion of the carbon. A standard instrument for the
      group parameter AOX (adsorbable organic halogens) was used for the combustion.
      The halides formed were trapped in an alkaline solution and analysed by capillary
      zone electrophoresis. The method described enabled determination of sub-ppb
      concentrations of the group parameters AOCl, AOBr and AOI (adsorbable organic
      chlorine, bromine and iodine, respectively). Analysis of rain and snow collected
      at different sites in Europe showed that organochlorines were responsible for the
      major part of the AOX content in all samples collected. Organically bound bromine
      was found in sub-ppb concentrations in all of the samples, whereas organic iodine
      was detected in only two of the samples.

PMID- 10903111
TI  - Determination of the molecular weight of fulvic acids by UV/VIS spectroscopy
AB  - Partial least squares (PLS) modeling was applied to investigate number-average
      molecular weights (Mn) and weight-average molecular weights (Mw) of fulvic acids
      (FAs) in relation to the corresponding UV/VIS spectra. The Mn and Mw values were
      determined by size exclusion chromatography (SEC). The impact of pH control,
      wavelength range and density as well as smoothing and derivation of spectra were
      tested. It was found that PLS models based on absorbance spectra can be a fast
      and powerful complement to existing techniques employed for determination of
      molecular weights of FAs. Control of pH of the FA solutions is important for the
      performance of the models. The models were also compared with the best univariate
      alternatives.

PMID- 10903112
TI  - Chlorinated hydrocarbons in Scots pine needles in northern Britain
AB  - Concentrations of 4 chlorinated hydrocarbons, C2H3Cl3 (1,1,1-trichloroethane),
      CCl4 (tetrachloromethane), C2HCl3 (trichloroethene) and C2Cl4 (tetrachloroethene)
      have been measured in needles of Scots pine (Pinus sylvestris L.) growing close
      to two industrial sites and in a rural area in northern Britain. Pentane extracts
      of pine needles sampled over 14 months were analysed using gas chromatography
      with electron capture detection. Geometric mean concentrations were not
      significantly different among the sites, with values (in ng g(-1) dry weight) of
      7-15 for C2H3Cl3, 3.2-6.5 for CCl4, 70-240 for C2HCl3 and 11-26 for C2Cl4. There
      was no evidence of accumulation with needle age, but more exposed sites (e.g.
      those higher in the canopy) showed significantly larger concentrations. The
      influence of possible local sources could not be detected.

PMID- 10903113
TI  - Quantification of the dissolved organic matter effect on the sorption of
      hydrophobic organic pollutant: application of an overall mechanistic sorption
      model
AB  - This study presents an overall sorption model to estimate the sorption
      equilibrium coefficients of hydrophobic organic pollutants for heterogeneous
      aquatic systems. This proposed model combines a series of sorption equilibrium
      relationships including the adsorption of dissolved organic matters on
      particulates, the binding between organic pollutants and dissolved organic
      matters, and the sorption of organic pollutants on particulates with or without
      the presence of dissolved organic matters. By using this model, variations among
      the sorption equilibrium coefficients with the concentrations of dissolved
      organic matters are obtained. Also discussed herein are case studies involving
      pollutants having a wide spectrum of K(ow)s, different types of dissolved organic
      matters, different pH values and ionic strengths. In most of the case studies,
      the sorption equilibrium coefficients initially increase with the-concentrations
      of dissolved organic matters and, then, decrease after reaching a maximum value.
      This study also addresses the relative errors of partition coefficients
      attributed to the negligence of the effect caused by the dissolved organic
      matter, the so-called third-phase effect.

PMID- 10903114
TI  - Analysis of volatile fatty acids in wastewater collected from a pig farm by a
      solid phase microextraction method.
AB  - The main purpose of this study is to develop a reliable Solid Phase
      Microextraction (SPME) method for monitoring the concentration of volatile fatty
      acid (VFA) in the wastewater collected from pig farms. Ten volatile fatty acid
      species were spiked in 2 ml of swine wastewater and extracted with a carbowax
      coated extraction fiber to evaluate the accuracy and precision of the method. The
      fiber was introduced into a gas chromatography system by thermal desorption and
      detected by a mass spectrometer detector. The estimated method detection limits
      ranged from 11.5 mM/L for formic acid to 0.03 mM/L for heptanoic acid. The method
      is more sensitive than the sample direct injection method. The percentage
      recovery of analytes ranged from 77.3 for propanoic acid to 114.1 for formic acid
      at the spike level of 19.09 mM/L. The compound absorption rate varied
      significantly with the fiber absorption time for n-Valeric, isocaproic, n-caproic
      and heptanoic acids. An SPME method with twenty minutes fiber absorption and
      three minutes thermal desorption was tested in this study and resulted in good
      reproducibility for analyzing VFAs in swine wastewater. The method may be applied
      for scanning a wide spectrum of polar organic compounds in environmental samples.

PMID- 10903115
TI  - Degradation of reactive dyes I. A comparative study of ozonation, enzymatic and
      photochemical processes
AB  - The environmental problems associated with textile activities are represented
      mainly by the extensive use of organic dyes. A great number of these compounds
      are recalcitrant and shown carcinogenic or mutagenic character. In this work
      three processes were studied for degradation of an anthraquinone dye (C.I.
      reactive blue-19). The ozonation process leads to complete decolorization with a
      very short reaction time; however, effective mineralization of the dye was not
      observed. The enzymatic process promotes quick decolorization of the dye;
      nevertheless, maximum decolorization degrees of about 30% are insignificant in
      relation to the decolorization degree achieved by the other processes. The best
      results were found for the photocatalytical process. The use of ZnO or TiO2 as
      photocatalysts, permits total decolorization and mineralization of the dye with
      reaction times of about 60 min.

PMID- 10903116
TI  - Induction of steroidal hydroxylase activity by plant defence compounds in the
      filamentous fungus Cochliobolus lunatus
AB  - We investigated the hypothesis that the endogenous role of the commercially
      important inducible steroid hydroxylase cytochrome P450s of fungi was in defense
      against plant toxophores/secondary metabolites. Two plant defense compounds, the
      aglycones tomatidine and solanidine, the steroidal glycoalkaloid alpha-tomatine
      and the triterpene saponin beta-escin were tested as inducers of 11beta/14alpha
      steroid hydroxylase in the filamentous fungus Cochliobolus lunatus. The extracts
      of saponins from the roots of Primula veris and green oat leaves were also tested
      as inducers of 11beta/14alpha-hydroxylation activity in progesterone
      biotransformation with the same fungus. Induction of steroid hydroxylase and
      inhibition of activity in some cases support our hypothesis that their endogenous
      function is in biochemical defence against secondary metabolites. 4-Pregnene
      3,11,20-trione was added as a substrate for biotransformation with C. lunatus. We
      isolated from culture broth 14alpha-hydroxy-4-pregnene-3,11,20-trione, and the
      hitherto unreported compounds, 7alpha,14alpha-dihydroxy-4-pregnene-3,11,20-trione
      and 7alpha-hydroxy-pregna-4,8(14)-diene-3,11,20-trione.

PMID- 10903117
TI  - Utilization of TiO2 deposited on glass plates for removal of metals from aqueous
      wastes
AB  - Glass plates coated with TiO2 were used in a photocatalytic process to collect
      mercury, lead, copper and cadmium from aqueous solutions containing individual
      metals and mixtures. Stripping voltammetry, verified to achieve 1-10 ppb
      detection limits, was used to show that individual metals at concentrations of
      1000 to 5200 ppb were reduced to undetectable levels in 3 to 55 min. Capillary
      electrophoresis (CE) with 8-hydroxyquinoline-5-sulfonic acid as complexing agent
      was used when appropriate, since it could quantitate all four metals under study
      in one run although it was less sensitive. It was demonstrated that 100 mL
      solutions containing 10 ppm of each of the four metals could be treated with a 10
      cm2 TiO2-coated plate to leave undetectable metal concentrations in one hour.
      Stripping voltammetry using carbon electrodes coated with mercury films was
      estimated to generate daily about 1.1 L of aqueous waste containing 0.1 ppm of
      each metal. The results indicate the feasibility of assembling an apparatus
      capable of treating the waste generated by stripping voltammetry to render the
      latter suitable for routine on-site analyses without environmental concern. Data
      were also obtained to show the effectiveness in treating silver containing
      solutions, indicating suitability of the photocatalytic process in treating
      photographic processing wastes.

PMID- 10903118
TI  - A field study to compare performance of stainless steel research monitoring wells
      with existing on-farm drinking water wells in measuring pesticide and nitrate
      concentrations.
AB  - Existing drinking water wells are widely used for the collection of ground water
      samples to evaluate chemical contamination. A well comparison study was conducted
      to compare pesticide and nitrate-N data from specially designed stainless steel
      research monitoring wells with data from nearby existing on-farm drinking water
      wells. Results could help to determine whether adequate information concerning
      ground water contamination can be obtained from existing drinking water wells for
      use in making pollutant control decisions. The study was conducted during 1993
      1994 in the Little Coharie Watershed, a 158 square mile area located in the
      coastal plain of eastern North Carolina. Statistical analysis indicated that
      research monitoring wells provided a greater probability of detecting pesticides
      in ground water than existing on-farm wells. Atrazine was the most frequently
      detected pesticide found in all wells, followed in order by fluometuron,
      carbofuran, metolachlor, alachlor, carbaryl, butylate, chlorothalonil, linuron
      and simazine. Ninety-seven percent of all wells had observed concentrations of
      nitrate-N, ranging from 0.1 to 30.1 mg/L. There was not a significant difference
      between research wells and existing wells for monitoring nitrate-N. Based on
      results of this study, existing drinking water wells can be used for monitoring
      nitrate; however, specialized stainless steel monitoring wells should be used for
      monitoring pesticides in ground water.

PMID- 10903119
TI  - Thermochemical studies of the toxic actions of heavy metal ions on Rhizopus
      nigricans.
AB  - By using a LKB2277 BioActivity Monitor (heat conduction microcalorimeter),
      stopped-flow method, the thermogenetic curves of Rhizopus nigricans growth at 25
      degrees C inhibited by four kinds of heavy metal ions are determined, parameters
      such as growth rate constants k, inhibitory ratio I, half inhibitory
      concentration IC50 et al. are obtained. The experimental results show that heavy
      metal ions can inhibit Rhizopus nigricans growth obviously, low concentration of
      Cu2+ has promoting action. The inhibitory sequence is Cd2+ > Hg2+ > Pb2+ > Cu2+,
      half inhibitory concentration of them are Cd+ 0.8 micro g x ml(-1), Hg2+ 1.7
      micro g x ml(-1), Pb2+ 48.0 micro g x ml(-1), Cu2+ 110 micro g x ml(-1). This
      microclorimetric bioassay for acute cellular toxicity is based on metabolic heat
      evolution from cultured cells. The assay is quantitative, inexpensive, and
      versatile; moreover, toxicological information can be obtained with cell from
      other species of interest.

PMID- 10903120
TI  - Heavy metals in atmospheric surrogate dry deposition
AB  - This paper describes a methodological approach for the assessment of the amount
      of surrogate dry deposition of several toxic heavy metals (Cd, Cr, Cu, Ni, Pb, V,
      Zn) associated with atmospheric particulate matter at ground level. The
      objectives of the study were twofold: i) the evaluation of several techniques for
      the digestion of dry deposition samples for trace metal analysis; ii) the
      comparison of the results from two samplers with different collecting surfaces. A
      dry solid surface sampler (DRY sampler, Andersen--USA) and a water layer surface
      sampler (DAS sampler--MTX Italy) were employed. The samples were collected over a
      one-year period in an urban site of Bologna (northern Italy). A description is
      given of the complete procedure, from sampling to data elaboration, including
      sample storage, digestion and analytical methods. According to the results
      obtained with three different digestion techniques (Teflon bomb, microwave
      digester and Teflon flask with vapour cooling system), the highest recovery rate
      was achieved by the Teflon bomb procedure employing an NBS 1648 Standard
      Reference Material; 90-95% of the elements considered were recovered by
      dissolution in a pressurized Teflon bomb with an HNO3-HF mixture. Given these
      results, the technique was adopted for dry deposition sample digestion. On the
      basis of the amount of heavy metals measured as monthly deposition fluxes
      (microg/m2), the collecting efficiency of the DAS sampler for a number of
      elements was found to be as much as two to three times greater than that of the
      DRY sampler.

PMID- 10903122
TI  - Shifts in herbicide tolerance in paddy field periphyton following herbicide
      application
AB  - Herbicide susceptibility was examined in various algal strains isolated from
      herbicide-treated and untreated paddy fields. Diatom strains showed obvious
      tolerance to the herbicides simetryn and pretilachlor irrespective of herbicide
      exposure, while the susceptibility of green algae mostly reflected their history
      of herbicide exposure. Cross-resistance was also induced in some algae. Rapid
      development of herbicide tolerance indicated that the tolerance seemed to be
      conferred by tolerant strains already present in the communities. Thus, changes
      in genetic composition within a population seem to be the main mechanism by which
      paddy periphyton gain herbicide tolerance.

PMID- 10903121
TI  - A model for non-specific toxicity with aquatic organisms over relatively long
      periods of exposure time.
AB  - Experimental data have shown that the internal lethal concentrations of
      halobenzenes for aquatic organisms decreased with exposure time. In this paper, a
      model based on the concept of life expectancy reduction was developed to describe
      this relationship. The model was verified with experimental data for fish
      (Gambusia affinis) and juvenile crab (Porturius pelagicus(L)). It is proposed
      that long term non-specific toxicity can be measured as the reduction of the life
      expectancy of the exposed organism per unit internal concentration (or volume
      fraction) of the toxic compound. The model can be used to estimate internal
      lethal concentration at any given exposure period and vice versa. The model can
      also be used to estimate chronic values of the internal concentration, of the
      toxicants. It provides a useful tool for assessment of environmental risk of
      organic compounds in aquatic ecosystems.

PMID- 10903123
TI  - Autosomal recessive nonsyndromic neurosensory deafness at DFNB1 not associated
      with the compound-heterozygous GJB2 (connexin 26) genotype M34T/167delT.
AB  - Previous studies of the gap-junction beta-2 subunit gene GJB2 (connexin 26) have
      suggested that the 101T-->C (M34T) nucleotide substitution may be a mutant allele
      responsible for recessive deafness DFNB1. This hypothesis was consistent with
      observations of negligible intercellular coupling and gap-junction assembly of
      the M34T allele product expressed in Xenopus oocytes and HeLa cells. The results
      of our current study of a family cosegregating the 167delT allele of GJB2 and
      severe DFNB1 deafness demonstrate that this phenotype did not cosegregate with
      the compound-heterozygous genotype M34T/167delT. Since 167delT is a null allele
      of GJB2, this result indicates that the in vivo activity of a single M34T allele
      is not sufficiently reduced to cause the typical deafness phenotype associated
      with DFNB1. This observation raises the possibility that other GJB2 missense
      substitutions may not be recessive mutations that cause severe deafness and
      emphasizes the importance of observing cosegregation with deafness in large
      families to confirm that these missense alleles are mutant DFNB1 alleles.

PMID- 10903124
TI  - OTOF encodes multiple long and short isoforms: genetic evidence that the long
      ones underlie recessive deafness DFNB9.
AB  - We have recently reported that OTOF underlies an autosomal recessive form of
      prelingual sensorineural deafness, DFNB9. The isolated 5-kb cDNA predicted a
      1,230 amino acid (aa) C-terminus membrane-anchored cytosolic protein with three
      C2 domains. This protein belongs to a family of mammalian proteins sharing
      homology with the Caenorhabditis elegans fer-1. The two other known members of
      this family, dysferlin and myoferlin, both have six predicted C2 domains. By
      northern blot analysis, a 7-kb otoferlin mRNA could be detected in the human
      brain. We isolated the corresponding cDNA, which is expected to encode a 1,977-aa
      long form of otoferlin with six C2 domains. A 7-kb cDNA derived from the murine
      orthologous gene, Otof, was also identified in the inner ear and the brain. The
      determination of the exon-intron structure of the human and murine genes showed
      that they are composed of 48 coding exons and extend approximately 90 kb and
      approximately 80 kb, respectively. Alternatively spliced transcripts could be
      detected that predict several long isoforms (six C2 domains) in humans and mice
      and short isoforms (three C2 domains) only in humans. Primers were designed to
      explore the first 19 OTOF exons, henceforth permitting exploration of the
      complete coding sequence of the gene in DFNB9 patients. In a southwestern Indian
      family affected by DFNB9, a mutation in the acceptor splice site of intron 8 was
      detected, which demonstrates that the long otoferlin isoforms are required for
      inner ear function.

PMID- 10903125
TI  - Early-life programming of susceptibility to dysregulation of glucose metabolism
      and the development of Type 2 diabetes mellitus.
AB  - There is increasing epidemiological evidence in humans which associates low
      birthweight with later metabolic disorders, including insulin resistance and
      glucose intolerance. There is evidence that nutritional and hormonal factors
      (e.g. maternal protein restriction, exposure to excess maternal glucocorticoids)
      markedly influence intra-uterine growth and development. A picture is also
      emerging of the biochemical and physiological mechanisms that may underlie these
      effects. This review focuses on recent research directed towards understanding
      the molecular basis of the relationship between indices of poor early growth and
      the subsequent development of glucose intolerance and Type 2 diabetes mellitus
      using animal models that attempt to recreate the process of programming via an
      adverse intra-uterine or neonatal environment. Emphasis is on the chain of events
      and potential mechanisms by which adverse adaptations affect pancreatic-beta-cell
      insulin secretion and the sensitivity to insulin of key metabolic processes,
      including hepatic glucose production, skeletal-muscle glucose disposal and
      adipose-tissue lipolysis. Unravelling the molecular details involved in metabolic
      programming may provide new insights into the pathogenesis of impaired
      glucoregulation and Type 2 diabetes.

PMID- 10903127
TI  - Cathepsin-6, a novel cysteine proteinase showing homology with and co-localized
      expression with cathepsin J/P in the labyrinthine layer of mouse placenta.
AB  - A novel cysteine proteinase, cathepsin-6, was isolated by RNA differential
      display from mouse placenta. Cathepsin-6 showed the highest homology with
      cathepsin J (same as P) and L. The structural features including the catalytic
      triad of the C1 proteinase family were well conserved in cathepsin-6. The
      expression of cathepsin-6 and cathepsin J/P was restricted in labyrinthine
      trophoblasts of the placenta.

PMID- 10903128
TI  - Studies on the differential inhibition of glutathione conjugate formation of (+)
      anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide and 1-chloro-2,4-dinitrobenzene
      in V79 Chinese hamster cells.
AB  - V79 Chinese hamster cells have previously been shown to lack the capacity to
      detoxify the mutagenic and carcinogenic compound (+)-anti-benzo[a]pyrene 7,8
      dihydrodiol 9,10-epoxide [(+)-anti-BPDE] by Pi class glutathione transferase
      (GSTPi)-catalysed conjugation with GSH, although these cells contain such an
      enzyme [Romert, Dock, Jenssen and Jernstrom (1989) Carcinogenesis 10, 1701-1707;
      Swedmark, Romert, Morgenstern and Jenssen (1992) Carcinogenesis 13, 1719-1723;
      Swedmark and Jenssen (1994) Gene 139, 251-256]. Previous findings also indicate
      that these results do not depend on an inactive GSTPi enzyme, since V79 cells
      conjugate 1-chloro-2, 4-dinitrobenzene (CDNB) with GSH, but more likely on (a)
      factor(s) that inhibit(s) V79 GSTPi selectively [Swedmark, Jernstrom and Jenssen
      (1996) Biochem. J. 318, 533-538]. The present study demonstrates that both human
      and V79 recombinant GSTPi enzymes are inhibited with respect to conjugating (+)
      anti-BPDE, but not CDNB, after pre-incubation with V79-cell extract, but not with
      MCF-7-cell extract. In addition, it was found that the inhibition is dependent on
      the amount of cell extract present and that the factor(s) is heat-resistant and
      has a molecular mass of less than 10 kDa, suggesting that the factor(s) is (are)
      non-proteinaceous in nature.

PMID- 10903129
TI  - 14-3-3 proteins are required for the inhibition of Ras by exoenzyme S.
AB  - 14-3-3 proteins play a regulatory role and participate in both signal
      transduction and checkpoint control pathways. 14-3-3 proteins bind phosphoserine
      ligands, such as Raf-1 kinase and Bad, by recognizing the phosphorylated
      consensus motif, Arg-Ser-Xaa-pSer-Xaa-Pro (where 'Xaa' represents 'any residue',
      and 'pSer' is 'phosphoserine'). However, 14-3-3 proteins must bind
      unphosphorylated ligands, such as glycoprotein Ibalpha and Pseudomonas aeruginosa
      exoenzyme S (ExoS), since it has been suggested that specific residues of 14-3-3
      proteins are required for activation of ExoS. Furthermore, an unphosphorylated
      peptide derived from a phage display library inhibited the binding of both ExoS
      and Raf-1 to 14-3-3, and bound within the same conserved amphipathic groove on
      the surface of 14-3-3 as the Raf-derived phosphopeptide (pS-Raf-259). In the
      present study we identify the interaction site on ExoS for 14-3-3, and show that
      ExoS and 14-3-3 do indeed interact in vivo. In addition, we show that this
      interaction is critical for the ADP-ribosylation of Ras by ExoS, both in vitro
      and in vivo. Loss of the 14-3-3 binding site on ExoS results in an ExoS molecule
      that is unable to efficiently inactivate Ras, and displays reduced killing
      activity.

PMID- 10903131
TI  - The specificity of the protein kinase C alpha, betaII and gamma isoforms as
      assessed by an unnatural alcohol-appended peptide library.
AB  - Previous studies using conventional peptide-based libraries have demonstrated
      that homologous protein-processing enzymes [e.g. the alpha, betaII and gamma
      isoforms of protein kinase (PKC)] typically display identical amino acid
      consensus sequences. These observations have hampered the acquisition of
      selective synthetic substrates for the individual members of these enzyme
      families. We describe here a parallel synthesis strategy, readily adaptable to
      the preparation of large libraries, that has led to the emergence of the first
      examples of selective substrates for the conventional PKC isoforms. In addition,
      we have found that a wide variety of structurally diverse N-appended alcohol
      containing residues, including tyrosine, serve as substrates for the PKC alpha,
      betaII and gamma isoforms. This broad active-site substrate specificity with
      respect to both natural and unnatural residues may prove to be especially
      applicable to the construction of transition-state analogues and suicide
      substrates, species that often require the presence of structurally elaborate
      functionality.

PMID- 10903130
TI  - Rapid degradation of the presequence of the f1beta precursor of the ATP synthase
      inside mitochondria.
AB  - We have investigated the fate of the presequence of an overexpressed protein
      derived from the precursor of the F(1)beta subunit of ATP synthase after import
      and processing in mitochondria. Our studies revealed a rapid degradation of the
      presequence inside mitochondria catalysed by matrix-located protease(s). In
      contrast, the mature portion of the precursor was not degraded. This is the first
      experimental evidence of the rapid degradation of a mitochondrial presequence in
      organello after in vitro import and processing.

PMID- 10903132
TI  - Structure-function relationships in novel peptide dodecamerswith broad-spectrum
      bactericidal and endotoxin-neutralizing activities.
AB  - A series of designed peptide 33-mers (betapep peptides) areknown to be
      bactericidal [Mayo, Haseman, Ilyina and Gray (1998)Biochim. Biophys. Acta 1425,
      81-92]. Here dodecapeptides (SC-1-SC-8), which 'walk through' the sequence
      ofbetapep-25, were investigated for their ability to kill Gram-negativeand 
      positive bacteria and to neutralize endotoxin. SC-4 (KLFKRHLKWKI I-NH(2); the 
      NH(2) at the right of each sequenceindicates amidation of the C-terminal
      carboxylate group) is the mosteffective, more so than betapep-25, at killing Gram
      negative bacteriawith nanomolar LD(50) values. Against Gram-positive bacteria,SC
      4 also shows good activity with submicromolar LD(50)values. Leakage studies
      indicate rapid bacterial membrane permeability,with t(1/2) valuesof 10-15 min. SC
      4 in the micromolar range also effectivelyneutralizes endotoxin and is not
      haemolytic below 10(-4)M. For all SC peptides, CD and NMR data indicate the
      presence of both 3(10)- and alpha-helix. For SC-4, nuclear-Overhauser-effect
      based computational modelling yields an amphipathic helix with K1, K4,R5, and K8
      arrayed on the same face (K is lysine, R is arginine). Activity differences among
      SC peptides and single-site variants of SC-4allow some structure-function
      relationships to be deduced. Relative to other known bactericidal peptides in the
      linear peptide,helix-forming category, SC-4 is the most potent broad
      spectrumantibacterial identified to date. The present study contributes to
      thedevelopment of agents involved in combating the ever-recurring problemof drug
      resistant micro-organisms.

PMID- 10903126
TI  - Role of plasma membrane transporters in muscle metabolism.
AB  - Muscle plays a major role in metabolism. Thus it is a major glucose-utilizing
      tissue in the absorptive state, and changes in muscle insulin-stimulated glucose
      uptake alter whole-body glucose disposal. In some conditions, muscle
      preferentially uses lipid substrates, such as fatty acids or ketone bodies.
      Furthermore, muscle is the main reservoir of amino acids and protein. The
      activity of many different plasma membrane transporters, such as glucose carriers
      and transporters of carnitine, creatine and amino acids, play a crucial role in
      muscle metabolism by catalysing the influx or the efflux of substrates across the
      cell surface. In some cases, the membrane transport process is subjected to
      intense regulatory control and may become a potential pharmacological target, as
      is the case with the glucose transporter GLUT4. The goal of this review is the
      molecular characterization of muscle membrane transporter proteins, as well as
      the analysis of their possible regulatory role.

PMID- 10903133
TI  - 4-Hydroxy-2(E)-nonenal enantiomers: (S)-selective inactivation of glyceraldehyde
      3-phosphate dehydrogenase and detoxification by rat glutathione S-transferase A4
      4.
AB  - The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase was irreversibly
      and (S)-selectively inactivated by the enantiomers of racemic 4-hydroxy-2(E)
      nonenal (HNE), a reactive product released from biomembranes by lipid
      peroxidation in cells. Rates of the enzyme inactivations were 1.7, 3.0, and 6.0
      M(-1).s(-1) for (R)-, racemic and (S)-HNEs respectively. In rat liver cytosol the
      HNE was detoxified 2.5-fold more (S)-selectively by GSH conjugation and 2. 4-fold
      more (R)-selectively by NADH-dependent reduction mediated by alcohol
      dehydrogenase (ADH) than the opposite enantiomers. However, in the cytosol the
      GSH conjugation of (R)-HNE proceeded at a much higher rate than did its ADH
      mediated reduction. The minor glutathione S-transferase (GST) isoform, A4-4, in
      the rat (r) liver had a major role in the cytosolic (S)-selective GSH
      conjugation. The catalytic efficiency, k(cat)/K(m), of purified rGSTA4-4 was 4
      fold higher for (S)-HNE than for (R)-HNE; the K(m) was 3-fold higher for (R)-HNE
      than for (S)-HNE. (S)-HNE was preferentially detoxified to (R)-HNE by rGSTA4-4
      when racemic HNE was used as a substrate.

PMID- 10903135
TI  - Diastereoisomeric analogues of gramicidin S: structure, biologicalactivity and
      interaction with lipid bilayers.
AB  - Analogues of a structurally equivalent version of theantimicrobial decameric
      cyclic peptide gramicidin S, GS10 [cyclo-(Val-Lys-Leu-d-Tyr-Pro)(2)], were
      designed to study theeffect of distortion in the beta-sheet/beta-turn structure
      of thecyclic peptide on its biological activity. In one approach, thehydrophobic
      nature of GS10 was conserved, and single amino acids in itsbackbone were replaced
      systematically with their correspondingenantiomers to give five diastereoisomeric
      analogues. In a relatedapproach, a more basic and hydrophilic analogue of GS10
      [cyclo-(Lys-Val-Lys-d-Tyr-Pro(5)-Lys-Leu-Lys-d-Tyr-Pro(10))], together with two
      of itsmonosubstituted diastereoisomeric analogues (featuring d-Lys(1) or d-Val(2)
      respectively), weresynthesized. CD spectra were measured in a variety of
      environments,i.e. aqueous, aqueous trifluoroethanol and those containing
      SDSmicelles or phospholipid vesicles. In comparison with GS10 spectra, CDspectra
      of both groups of analogues in these environments exhibitedstructural distortion.
      Moreover, compared with GS10, antimicrobial andhaemolytic activities of the
      analogues were drastically decreased, implying the existence of a threshold
      minimum amphipathicity foreffective biological activity. However, in both groups
      of analogues,there was a correlation between amphipathicity and antimicrobial
      andhaemolytic activities. In the second group of analogues, bothelectrostatic and
      hydrophobic factors were related to theirantimicrobial and haemolytic activities.
      In order to gain an insightinto the nature of the biological activity of the two
      classes of cyclicpeptides, the relationship of their structure to interaction
      with lipidmembranes, and the implied mechanisms, were analysed in some detail
      inthe present study.

PMID- 10903134
TI  - Vacuolar proton pyrophosphatase activity and pyrophosphate (PPi) in Toxoplasma
      gondii as possible chemotherapeutic targets.
AB  - The addition of PP(i) promoted the acidification of a subcellular compartment in
      cell homogenates of Toxoplasma gondii tachyzoites, implying the presence of a
      proton-translocating pyrophosphatase. The proton gradient was collapsed by
      addition of the K(+)/H(+) antiporter nigericin, and was also inhibited by
      addition of the PP(i) analogue aminomethylenediphosphonate (AMDP). Both proton
      transport and PP(i) hydrolysis were dependent upon K(+), but Na(+) caused partial
      inhibition of these activities. PP(i) hydrolysis was sensitive in a dose
      dependent manner to AMDP, imidodiphosphate, NaF and to the thiol reagent N
      ethylmaleimide. This activity was unaffected by common inhibitors of
      phosphohydrolases, except that NaO(3)V (sodium orthovanadate) stimulated the
      activity by 87%. Immunofluorescence microscopy, using antisera raised against
      conserved peptide sequences of a plant vacuolar pyrophosphatase, suggested that
      the pyrophosphatase in T. gondii tachyzoites was located in the plasma membrane
      and intracellular vacuoles of the parasite. High-field (31)P-NMR spectroscopy
      showed that PP(i )was more abundant than ATP in tachyzoites. Bisphosphonates
      (PP(i) analogues), drugs that are used in the treatment of bone diseases,
      inhibited proton transport and PP(i) hydrolysis in tachyzoite homogenates, and
      also inhibited intracellular proliferation of tachyzoites in tissue culture
      cells.

PMID- 10903136
TI  - Conformational changes in activated protein C caused by binding of the first
      epidermal growth factor-like module of protein S.
AB  - The first epidermal growth factor-like module of human plasma protein S (EGF1,
      residues 76-116) was chemically synthesized and tested for its ability to inhibit
      the anticoagulant cofactor activity of protein S for the anticoagulant protease,
      activated protein C (APC). EGF1 completely inhibited the stimulation of APC
      activity by protein S in plasma coagulation assays, with 50% inhibition at
      approx. 1 microM+ EGF1, suggesting direct binding of EGF1 to APC. To investigate
      a direct interaction between EGF1 and APC, fluorescence resonance energy transfer
      (FRET) experiments were employed. APC labelled in the active site with
      fluorescein as the donor, and phospholipid vesicles containing octadecylrhodamine
      as the acceptor, showed that EGF1 association with APC caused an increase in
      energy transfer consistent with a relocation of the active site of APC from 94 A
      (9.4 nm) to 85 A above the phospholipid surface (assuming kappa(2)=2/3). An
      identical increase in energy transfer between the APC active site-bound
      fluorescein and phospholipid-bound rhodamine was obtained upon association of
      protein S or protein S-C4b-binding protein complex with APC. The latter suggests
      the presence of a ternary complex of protein S-C4b-binding protein with APC on
      the phospholipid surface. To confirm a direct interaction of EGF1 with APC,
      rhodamine was covalently attached to the alpha-N-terminus of EGF1, and binding of
      the labelled EGF1 to APC was directly demonstrated using FRET. The data suggested
      a separation between the active site of APC and the N-terminus of EGF1 of 76 A
      (kappa(2)=2/3), placing the APC-bound protein S-EGF1 close to, but above, the
      phospholipid surface and near the two EGF domains of APC. Thus we provide direct
      evidence for binding of protein S-EGF1 to APC and show that it induces a
      conformational change in APC.

PMID- 10903137
TI  - Regulation of interleukin-6 gene expression by pro-inflammatory cytokines in a
      colon cancer cell line.
AB  - The two carcinoma cell lines HeLa and HTM-29 show different behaviour in terms of
      interleukin-6 (IL-6) production. Analyses of secreted IL-6 by ELISA and of IL-6
      mRNA by reverse transcription-PCR revealed that, whereas HeLa cells produced high
      levels of IL-6 in response to tumour necrosis factor-alpha (TNF-alpha) and IL
      1beta, the HTM-29 cell line failed to produce both IL-6 protein and mRNA.
      Nevertheless, the transcription factors nuclear factor-kappaB (NF-kappaB) and NF
      IL6, the main factors involved in IL-6 gene transcriptional activation by
      cytokines, were activated in both cell lines after treatment with TNF-alpha or IL
      1beta. In order to verify that the lack of IL-6 expression in HTM-29 cells was
      not due to an endogenous IL-6 gene deficiency or to IL-6 mRNA instability, we
      carried out transient transfection assays with an IL-6 promoter-reporter
      construct. Strong activation of the IL-6 promoter by cytokines could be observed
      in HeLa cells, whereas no induction could be detected in cytokine-treated HTM-29
      cells. These cytokines induced a very strong stimulation of NF-kappaB-mediated
      transcription in HeLa cells transfected with a kappaB luceriferase reporter
      construct, whereas no induction could be detected in cytokine-stimulated HTM-29
      cells. Thus IL-6 promoter repression in HTM-29 cells probably results from a
      failure of cytokine-activated NF-kappaB to exert its transactivating activities.
      Western blotting experiments demonstrated that the lack of NF-kappaB-mediated
      transcription was not due to increased expression of IkappaB (inhibitor of NF
      kappaB) proteins in HTM-29 cells. Co-transfection experiments with the kappaB Luc
      reporter construct and the CBP [CREB (cAMP response element binding protein)
      binding protein] expression vector showed that the impairment in NF-kappaB
      dependent transcription did not result from a deficiency in the co-activator CBP.
      Interestingly, both NF-kappaB-mediated transcription and IL-6 promoter activation
      could be restored in HTM-29 cells by transfection with RelA. Furthermore, CBP
      could have a significant synergistic effect on exogenous RelA-mediated
      transcription. Since sequencing of the endogenous relA gene did not reveal any
      mutation, it is likely that repression of NF-kappaB-mediated transcription
      results from negative cross-talk between NF-kappaB and another nuclear factor
      specifically expressed or regulated by TNF-alpha in HTM-29 cells.

PMID- 10903138
TI  - Contraction inhibits insulin-stimulated insulin receptor substrate-1/2-associated
      phosphoinositide 3-kinase activity, but not protein kinase B activation or
      glucose uptake, in rat muscle.
AB  - The initial stages of insulin-stimulated glucose uptake are thought to involve
      tyrosine phosphorylation of insulin receptor substrates (IRSs), which recruit and
      activate phosphoinositide 3-kinase (PI 3-kinase), leading to the activation of
      protein kinase B (PKB) and other downstream effectors. In contrast, contraction
      stimulates glucose uptake via a PI 3-kinase-independent mechanism. The combined
      effects of insulin and contraction on glucose uptake are additive. However, it
      has been reported that contraction causes a decrease in insulin-stimulated IRS-1
      associated PI 3-kinase activity. To investigate this paradox, we have examined
      the effects of contraction on insulin-stimulated glucose uptake and proximal
      insulin-signalling events in isolated rat epitrochlearis muscle. Stimulation by
      insulin or contraction produced a 3-fold increase in glucose uptake, with the
      effects of simultaneous treatment by insulin and contraction being additive.
      Wortmannin completely blocked the additive effect of insulin in contracting
      skeletal muscle, indicating that this is a PI 3-kinase-dependent effect. Insulin
      stimulated recruitment of PI 3-kinase to IRS-1 was unaffected by contraction;
      however, insulin produced no discernible increase in PI 3-kinase activity in IRS
      1 or IRS-2 immunocomplexes in contracting skeletal muscle. Consistent with this,
      contraction inhibited insulin-stimulated p70(S6K) activation. In contrast,
      insulin-stimulated activation of PKB was unaffected by contraction. Thus, in
      contracting skeletal muscle, insulin stimulates glucose uptake and activates PKB,
      but not p70(S6K), by a PI 3-kinase-dependent mechanism that is independent of
      changes in IRS-1- and IRS-2-associated PI 3-kinase activity.

PMID- 10903139
TI  - Iron oxidation and hydrolysis reactions of a novel ferritin from Listeria
      innocua.
AB  - Iron deposition in the unusual 12-subunit ferritin from thebacterium Listeria
      innocua proceeds in three phases: a rapidfirst phase in which Fe(2+) binds to the
      apoprotein, P(Z) of charge Z, according to the postulatedreaction 2Fe(2+)+P(Z)-
      >[Fe(2)-P](Z+2)+2H(+), where[Fe(2)-P](Z+2) represents adinuclear iron(II) complex
      formed at each of the 12 ferroxidase centresof the protein; a second phase
      corresponding to oxidation of thisputative complex, i.e. [Fe(2)-P](Z+2)+1/2 O(2)-
      >[Fe(2)O-P](Z)+2H(+);and a third phase of iron(II) oxidation/mineralization, i.e.
      4Fe(2+)+O(2)+8H(2)O-->8FeOOH((s))+8H(+) [where FeOOH((s)) represents the hydrous
      ferric oxidemineral that precipitates from the solution], which occurs when iron
      isadded in excess of 24Fe(2+)/protein. In contrast with otherferritins, the
      ferroxidation reaction in L. innocua ferritinproceeds more slowly than the
      oxidation/mineralization reaction. Wateris the final product of dioxygen
      reduction in the 12-subunit L.innocua ferritin (the present work) and in the 24
      subunit Escherichia coli bacterioferritin, whereas H(2)O(2) is produced in 24
      subunit mammalian ferritins. Possible reasonsfor this difference are discussed.

PMID- 10903140
TI  - The heterodimeric amino acid transporter 4F2hc/y+LAT2 mediates arginine efflux in
      exchange with glutamine.
AB  - The cationic amino acid arginine, due to its positive charge, is usually
      accumulated in the cytosol. Nevertheless, arginine has to be released by a number
      of cell types, e.g. kidney cells, which supply other organs with this amino acid,
      or the endothelial cells of the blood-brain barrier which release arginine into
      the brain. Arginine release in mammalian cells can be mediated by two different
      transporters, y(+)LAT1 and y(+)LAT2. For insertion into the plasma membrane,
      these transporters have to be associated with the type-II membrane glycoprotein
      4F2hc [Torrents, Estevez, Pineda, Fernandez, Lloberas, Shi, Zorzano and Palacin
      (1998) J. Biol. Chem. 273, 32437-32445]. The present study elucidates the
      function and distribution of y(+)LAT2. In contrast to y(+)LAT1, which is
      expressed mainly in kidney epithelial cells, lung and leucocytes, y(+)LAT2 has a
      wider tissue distribution, including brain, heart, testis, kidney, small
      intestine and parotis. When co-expressed with 4F2hc in Xenopus laevis oocytes,
      y(+)LAT2 mediated uptake of arginine, leucine and glutamine. Arginine uptake was
      inhibited strongly by lysine, glutamate, leucine, glutamine, methionine and
      histidine. Mutual inhibition was observed when leucine or glutamine was used as
      substrate. Inhibition of arginine uptake by neutral amino acids depended on the
      presence of Na(+), which is a hallmark of y(+)LAT-type transporters. Although
      arginine transport was inhibited strongly by glutamate, this anionic amino acid
      was only weakly transported by 4F2hc/y(+)LAT2. Amino acid transport via
      4F2hc/y(+)LAT2 followed an antiport mechanism similar to the other members of
      this new family. Only preloaded arginine could be released in exchange for
      extracellular amino acids, whereas marginal release of glutamine or leucine was
      observed under identical conditions. These results indicated that arginine has
      the highest affinity for the intracellular binding site and that arginine release
      may be the main physiological function of this transporter.

PMID- 10903141
TI  - Inhibition of smooth-muscle myosin-light-chain phosphatase by Ruthenium Red.
AB  - Ruthenium Red (RuR) is widely used as an inhibitor of ryanodine receptor Ca(2+)
      release channels, but has additional effects such as the induction of Ca(2+)
      sensitization of contraction of permeabilized smooth muscles. To address the
      mechanism underlying this process, we examined the effects of RuR on
      contractility in permeabilized guinea-pig ileum and on the activity of myosin
      light-chain phosphatase (MP). RuR increased the force at submaximal [Ca(2+)] (pCa
      6.3) approx. 4-fold. This effect was not observed after thiophosphorylation of
      MP. RuR also seemed capable of preventing the thiophosphorylation of MP,
      suggesting a direct interaction of RuR with MP. Consistent with this possibility,
      smooth-muscle MP was inhibited by RuR in a concentration-dependent manner (IC(50)
      23 microM). Exogenous calmodulin significantly increased RuR-induced contraction
      at pCa 6.3 but had little effect on contraction induced by microcystin at this
      [Ca(2+)]. Ca(2+)-independent contraction was induced by RuR (EC(50) 843 microM)
      and by microcystin (EC(50) 59 nM) but the maximal force induced by RuR was
      smaller than that induced by microcystin. The addition of 300 microM RuR enhanced
      the contraction induced by 30 nM microcystin but markedly decreased that induced
      by 1 microM microcystin. Such a dual action of RuR on microcystin-induced effects
      was not observed in experiments using purified MP. We conclude that the RuR
      induced Ca(2+) sensitization of smooth-muscle contraction is due to the direct
      inhibition of MP by RuR.

PMID- 10903142
TI  - Fusion of the tissue factor extracellular domain to a tumour stroma specific
      single-chain fragment variable antibody results in an antigen-specific
      coagulation-promoting molecule.
AB  - Solid tumours growing beyond a size of 1-2 mm in diameter induce supporting
      connective tissue structures, the tumour stroma, comprising activated fibroblasts
      and newly formed blood vessels, embedded in an extracellular matrix. The
      selective destruction of this tissue or the inhibition of its function (e.g.
      tumour neoangiogenesis) may result in the destruction of tumour nodules, thus
      providing novel opportunities for tumour therapy. Our approach aims at an
      antibody-mediated induction of coagulation in tumour nodules to cut off their
      blood supply. As a target structure the fibroblast activation protein (FAP) is
      used, which is specifically and abundantly expressed on the activated fibroblasts
      of the tumour stroma. We constructed a fusion protein comprising a single-chain
      module of a FAP-specific humanized antibody [single-chain fragment variable
      (scFv) OS4] and the extracellular domain of human tissue factor. The fusion
      protein, designated TFOS4, was produced in the Proteus mirabilis protoplast
      expression system with a yield of 15 microg/ml. Biochemical characterization of
      TFOS4 revealed high-affinity binding to cellular FAP. Further, TFOS4 bound to
      factor VIIa and also exerted allosteric activation of factor VIIa. A complex of
      TFOS4 and factor VIIa bound to FAP-expressing cells efficiently generated
      activated factor X. Finally, cell-bound TFOS4 selectively induced plasma
      coagulation, implying its activity under physiological conditions, notably with
      relevant concentrations of coagulation factors and their natural inhibitors.
      These findings suggest that TFOS4 has the potential to increase the procoagulant
      state in a cell-type-specific fashion. No systemic coagulation or side effects
      were observed when TFOS4 was injected intravenously into normal mice, indicating
      the biosafety and specificity of the recombinant protein.

PMID- 10903143
TI  - Role of arg-410 and tyr-411 in human serum albumin for ligand binding and
      esterase-like activity.
AB  - Recombinant wild-type human serum albumin (rHSA), the single-residue mutants
      R410A, Y411A, Y411S and Y411F and the double mutant R410A/Y411A were produced
      using a yeast expression system. The recombinant proteins were correctly folded,
      as they had the same stability towards guanidine hydrochloride and the same CD
      spectrum as HSA isolated from serum (native HSA). Thus the global structures of
      the recombinant proteins are probably very similar to that of native HSA. We
      investigated, by ultrafiltration and CD, the high-affinity binding of two
      representative site II ligands, namely ketoprofen and diazepam. According to the
      crystal structure of HSA, the residues Arg-410 and Tyr-411 protrude into the
      centre of site II (in subdomain 3A), and the binding results showed that the
      guanidino moiety of Arg-410, the phenolic oxygen and the aromatic ring of Tyr-411
      are important for ketoprofen binding. The guanidino moiety probably interacts
      electrostatically with the carboxy group of ketoprofen, the phenolic oxygen could
      make a hydrogen-bond with the keto group of the ligand, and the aromatic ring may
      participate in a specific stacking interaction with one of or both of the
      aromatic rings of ketoprofen. By contrast, Arg-410 is not important for diazepam
      binding. The two parts of Tyr-411 interact favourably with diazepam, and probably
      do so in the same way as with ketoprofen. In addition to its unique ligand
      binding properties, HSA also possesses an esterase-like activity, and studies
      with p-nitrophenyl acetate as a substrate showed that, although Arg-410 is
      important, the enzymic activity of HSA is much more dependent on the presence of
      Tyr-411. A minor activity could be registered when serine, but not alanine or
      phenylalanine, was present at position 411.

PMID- 10903145
TI  - Structure and expression of a novel frizzled gene isolated from the developing
      mouse gut.
AB  - The Wnt/APC (adenomatous polyposis coli)/beta-catenin pathway plays a central
      role in the pathogenesis of colorectal cancer and probably also in normal
      development of the gastrointestinal tract. Frizzled proteins function as cell
      surface receptors for the Wnt family of extracellular ligands. Many components of
      the Wnt signalling pathway are expressed widely, and determinants of tissue
      specific functions are poorly understood. A better understanding of how Wnt
      signalling regulates tissue-specific development and gut epithelial homoeostasis
      requires characterization of the many components of this signalling pathway. We
      therefore wished to identify frizzled genes with limited tissue distribution of
      expression and isolated Mfz10, a novel member of the mouse family of frizzled
      genes, from the developing fetal gut. Highest levels of Mfz10 mRNA are detected
      throughout late embryonic development, in the brain, heart, lung and digestive
      tract. In adult mice Mfz10 mRNA is detected at highest levels in the heart, brain
      and lung. Expression in the adult gastrointestinal tract is much weaker, with
      higher levels in foregut derivatives (oesophagus and stomach) compared with
      regions derived from the fetal midgut and hindgut; particularly strong mRNA
      expression is observed in the squamous epithelium of the oesophagus. The amino
      acid sequence of Mfz10 is nearly identical to that of human FzE2 (also known as
      FzD2). Interestingly, mRNA levels of human FzD2 are reported to be up-regulated
      in oesophageal squamous cell carcinomas. These findings suggest a likely role for
      Mfz10 in the developing and adult foregut.

PMID- 10903144
TI  - Inhibition of mitogen-activated protein kinase by a Drosophila dual-specific
      phosphatase.
AB  - The Drosophila extracellular signal-regulated kinase (DERK) mitogen-activated
      protein kinase (MAPK) is involved in the regulation of multiple differentiation
      and developmental processes. Tight control of MAPK activity is critical for
      normal cell behaviour. We identified a novel Drosophila MAPK phosphatase (DMKP)
      cDNA from the expressed-sequence-tag database and characterized it. Analysis of
      the nucleotide sequence revealed an open reading frame encoding the 203-amino
      acid protein, with a calculated molecular mass of 23 kDa, which has a high amino
      acid sequence similarity with 'VH1-like' dual-specific phosphatases at the broad
      region near the catalytic sites. The expression of DMKP mRNA occurs from the late
      larval stages to adulthood in Drosophila development. The recombinant DMKP
      protein produced in yeast retained its phosphatase activity. When expressed in
      Schneider cells, DMKP dose-dependently inhibited DERK and Drosophila c-Jun N
      terminal kinase activities with high selectivity towards DERK. However, DMKP did
      not have any affect on Drosophila p38 activity. When DMKP was expressed in yeast,
      it down-regulated the fus1-lacZ trans-reporter gene of the pheromone MAPK pathway
      without any significant effect on the high-osmolarity-glycerol-response pathway.

PMID- 10903146
TI  - The membrane insertion of trichosanthin is membrane-surface-pH dependent.
AB  - Trichosanthin (TCS) is the active component extracted from Tianhuafen, a
      traditional herbal medicine that has been used for abortion in China for
      centuries. It belongs to the type-I ribosome-inactivating protein (RIP) family
      and can inactivate the eukaryotic ribosome through its RNA N-glycosidase
      activity. Recent studies have shown TCS to be multifunctional, its
      pharmacological properties including immunomodulatory, anti-tumour and anti-HIV
      activities. The membrane-insertion property of TCS is thought to be essential for
      its physiological effect, for it must get across the membrane before it can enter
      the cytoplasm and exert its RIP function. In this paper, the membrane-insertion
      mechanism of TCS was studied. The monolayer experiment revealed that TCS's
      membrane-insertion ability was dependent on low pH. Fluorescence spectroscopy
      using 1-anilinonaphthalene-8-sulphonic acid as a probe showed that low pH may
      induce the conformational change of TCS that leads to the hydrophobic-site
      exposure, and the CD result showed that this conformational change did not alter
      its secondary structure. Such conformational change leads to an intermediate
      state, called the 'molten globular state' by previous investigators. The pH
      dependent membrane insertion and conformational change were related by the fact
      that the optimal membrane-surface pH needed was the same for the two events. From
      these and other results, a membrane-insertion model was proposed.

PMID- 10903148
TI  - Crystal structure of the NADP+-dependent aldehyde dehydrogenase from Vibrio
      harveyi: structural implications for cofactor specificity and affinity.
AB  - Aldehyde dehydrogenase from the bioluminescent bacterium, Vibrio harveyi,
      catalyses the oxidation of long-chain aliphatic aldehydes to acids. The enzyme is
      unique compared with other forms of aldehyde dehydrogenase in that it exhibits a
      very high specificity and affinity for the cofactor NADP(+). Structural studies
      of this enzyme and comparisons with other forms of aldehyde dehydrogenase provide
      the basis for understanding the molecular features that dictate these unique
      properties and will enhance our understanding of the mechanism of catalysis for
      this class of enzyme. The X-ray structure of aldehyde dehydrogenase from V.
      harveyi has been solved to 2.5-A resolution as a partial complex with the
      cofactor NADP(+) and to 2. 1-A resolution as a fully bound 'holo' complex. The
      cofactor preference exhibited by different forms of the enzyme is predominantly
      determined by the electrostatic environment surrounding the 2'-hydroxy or the 2'
      phosphate groups of the adenosine ribose moiety of NAD(+) or NADP(+),
      respectively. In the NADP(+)-dependent structures the presence of a threonine and
      a lysine contribute to the cofactor specificity. In the V. harveyi enzyme an
      arginine residue (Arg-210) contributes to the high cofactor affinity through a pi
      stacking interaction with the adenine ring system of the cofactor. Further
      differences between the V. harveyi enzyme and other aldehyde dehydrogenases are
      seen in the active site, in particular a histidine residue which is structurally
      conserved with phosphorylating glyceraldehyde-3-phosphate dehydrogenase. This may
      suggest an alternative mechanism for activation of the reactive cysteine residue
      for nucleophilic attack.

PMID- 10903147
TI  - Involvement of the membrane lipid bilayer in sorting prohormone convertase 2 into
      the regulated secretory pathway.
AB  - Prohormone convertase 2 (PC2) is a neuroendocrine-specific protease involved in
      the intracellular maturation of prohormones and proneuropeptides. PC2 is
      synthesised as a proprotein (proPC2) that undergoes proteolysis, aggregation and
      membrane association during its transit through the regulated secretory pathway.
      We have previously shown that the pro region of proPC2 plays a key role in its
      aggregation and membrane association. To investigate this further, we determined
      the binding properties of a peptide containing amino acids 45-84 of proPC2
      (proPC2(45-84)) to trans-Golgi network/granule-enriched membranes from the AtT20
      cell line. Removal of peripheral membrane proteins or hydrolysis of integral
      membrane proteins did not affect the binding properties of proPC2(45-84). Rather,
      proPC2(45-84) was shown to bind to protein-free liposomes in a pH- and Ca(2+)
      dependent manner. To identify the component of the lipid bilayer involved in this
      membrane association, we used chromaffin-granule membranes and studied the
      binding properties of the endogenous PC2. Treatment of the membranes with
      saponin, a cholesterol-depleting detergent, failed to extract PC2 from the
      membranes, whereas chromogranin A (CgA) was removed. Treatment of the membranes
      with Triton X-100 yielded a low-density detergent-insoluble fraction enriched in
      PC2, but not CgA. The detergent-insoluble fraction also contained glycoprotein
      III, known to be part of the lipid rafts (membrane microdomains rich in
      sphingolipids). Finally, sphingolipid depletion of AtT20 cells resulted in the
      mis-sorting of PC2, suggestive of a link between the association of PC2 with
      lipid rafts in the membrane and its sorting into the regulated secretory pathway.

PMID- 10903149
TI  - Methylation and expression of amplified esterase genes in the aphid Myzus
      persicae (Sulzer).
AB  - Most populations of the aphid Myzus persicae have amplified genes (up to 80
      copies) encoding the insecticide-detoxifying esterase E4. This paper reports the
      analysis of methylation of the E4 gene and its flanking DNA with the use of
      methylation-sensitive restriction enzymes, CpG profiling and bisulphite
      sequencing. In combination these show that E4 has 5-methylcytosine confined to
      CpG doublets, as previously shown for vertebrate genomes; this is the first such
      report for an insect gene. The methylation is present within the gene but absent
      from upstream regions, including the 5' CpG-rich region around the start of
      transcription, and from 3' flanking DNA. Methylated E4 genes are expressed; loss
      of the 5-methylcytosine is correlated with a loss of transcription, although this
      is not accompanied by a global loss of the 5-methylcytosine present in the aphid
      genome. These results suggest that the methylation of E4 has a positive role in
      expression, and call into question the widely held view that methylation in
      invertebrate genomes is confined to regions that do not contain genes and that
      methylation is always associated with gene silencing.

PMID- 10903150
TI  - Regulation of cyclin-dependent kinase (Cdk) 2 Thr-160 phosphorylation and
      activity by mitogen-activated protein kinase in late G1 phase.
AB  - Mitogen-activated protein (MAP) kinases, p42(MAPK) and p44(MAPK), are central
      components of growth-promoting signalling pathways. However, how stimulation of
      MAP kinases culminates in cell-cycle progression is still poorly understood. Here
      we show that mitogenic stimulation of NIH 3T3 cells causes a sustained activation
      of MAP kinases, which lasts until cells begin progressing through the G(1)/S
      boundary. Furthermore, we observed that disruption of the MAP-kinase pathway with
      a selective MEK (MAP kinase/extracellular-signal-regulated protein kinase kinase)
      inhibitor, PD98059, prevents the activation of cyclin-dependent kinase (Cdk) 2
      and DNA synthesis, even when added during late G(1) phase, once the known
      mechanisms by which MAP kinase controls G(1) progression, accumulation of G(1)
      cyclins and degradation of Cdk inhibitors have already taken place. Moreover, we
      provide evidence indicating that MAP kinases control Cdk2 Thr-160 activating
      phosphorylation and function, possibly by regulating the activity of a Cdk
      activating kinase, thus promoting the re-initiation of DNA synthesis. These
      findings suggest the existence of a novel mechanism whereby signal-transducing
      pathways converging on MAP kinases can affect the cell-cycle machinery and,
      ultimately, participate in cell-growth control.

PMID- 10903151
TI  - Structure-function studies on hsp47: pH-dependent inhibition of collagen fibril
      formation in vitro.
AB  - Hsp47, a 47 kDa heat shock protein whose expression level parallels that of
      collagen, has been regarded as a collagen-specific molecular chaperone. Studies
      from other laboratories have established the association of Hsp47 with the
      nascent as well as the triple-helical procollagen molecule in the endoplasmic
      reticulum and its dissociation from procollagen in the Golgi. One of several
      roles suggested for Hsp47 in collagen biosynthesis is the prevention of
      aggregation of procollagen in the endoplasmic reticulum. However, no experimental
      evidence has been available to verify this suggestion. In the present study we
      have followed the aggregation of mature triple-helical collagen molecules into
      fibrils by using turbidimetric measurements in the absence and presence of Hsp47.
      In the pH range 6-7, fibril formation of type I collagen, as monitored by
      turbidimetry, proceeds with a lag of approx. 10 min and levels off by approx. 60
      min. The addition of Hsp47 at pH 7 effectively inhibits fibril formation at and
      above a 1:1 molar ratio of Hsp47 to triple-helical collagen. This inhibition is
      markedly pH-dependent, being significantly diminished at pH 6. CD and
      fluorescence spectral data of Hsp47 in the pH range 4.2-7.4 reveal a significant
      alteration in its structure at pH values below 6.2, with a decrease in alpha
      helix and an increase in beta-structure. This conformational change is likely to
      be the basis of the decreased binding of Hsp47 to collagen in vitro at pH 6.3 as
      well as its inability to inhibit collagen fibril formation at this pH. Our
      results also provide a functional assay for Hsp47 that can be used in studies on
      collagen and Hsp47 interactions.

PMID- 10903153
TI  - A hydrodynamic analysis of fish swimming speed: wake structure and locomotor
      force in slow and fast labriform swimmers.
AB  - Past study of interspecific variation in the swimming speed of fishes has focused
      on internal physiological mechanisms that may limit the ability of locomotor
      muscle to generate power. In this paper, we approach the question of why some
      fishes are able to swim faster than others from a hydrodynamic perspective, using
      the technique of digital particle image velocimetry which allows measurement of
      fluid velocity and estimation of wake momentum and mechanical forces for
      locomotion. We investigate the structure and strength of the wake in three
      dimensions to determine how hydrodynamic force varies in two species that differ
      markedly in maximum swimming speed. Black surfperch (Embiotoca jacksoni) and
      bluegill sunfish (Lepomis macrochirus) swim at low speeds using their pectoral
      fins exclusively, and at higher speeds switch to combined pectoral and caudal fin
      locomotion. E. jacksoni can swim twice as fast as similarly sized L. macrochirus
      using the pectoral fins alone. The pectoral fin wake of black surfperch at all
      speeds consists of two distinct vortex rings linked ventrally. As speed increases
      from 1.0 to 3.0 L s(-)(1), where L is total body length, the vortex ring formed
      on the fin downstroke reorients to direct force increasingly downstream, parallel
      to the direction of locomotion. The ratio of laterally to downstream-directed
      force declines from 0.93 to 0.07 as speed increases. In contrast, the sunfish
      pectoral fin generates a single vortex ring per fin beat at low swimming speeds
      and a pair of linked vortex rings (with one ring only partially complete and
      attached to the body) at maximal labriform speeds. Across a biologically relevant
      range of swimming speeds, bluegill sunfish generate relatively large lateral
      forces with the paired fins: the ratio of lateral to downstream force remains at
      or above 1.0 at all speeds. By increasing wake momentum and by orienting this
      momentum in a direction more favorable for thrust than for lateral force, black
      surfperch are able to swim at twice the speed of bluegill sunfish using the
      pectoral fins. In sunfish, without a reorientation of shed vortices, increases in
      power output of pectoral fin muscle would have little effect on maximum locomotor
      speed. We present two hypotheses relating locomotor stability, maneuverability
      and the structure of the vortex wake. First, at low speeds, the large lateral
      forces exhibited by both species may be necessary for stability. Second, we
      propose a potential hydrodynamic trade-off between speed and maneuverability that
      arises as a geometric consequence of the orientation of vortex rings shed by the
      pectoral fins. Bluegill sunfish may be more maneuverable because of their ability
      to generate large mediolateral force asymmetries between the left- and right-side
      fins.

PMID- 10903152
TI  - The pro-apoptotic protein death-associated protein 3 (DAP3) interacts with the
      glucocorticoid receptor and affects the receptor function.
AB  - The yeast two-hybrid system was used to isolate cDNAs encoding proteins that
      interact with the glucocorticoid receptor (GR) ligand-binding domain in a ligand
      dependent manner. One isolated cDNA encoded a fragment of death-associated
      protein 3 (DAP3), which has been implicated as a positive mediator of apoptosis.
      In vitro experiments showed that the full-length DAP3 also interacted with GR.
      The main interaction domain was mapped to the N-terminal region of DAP3 that had
      previously been shown to function in a dominant-negative fashion, protecting
      cells from apoptosis. Co-transfection experiments in COS-7 cells showed that DAP3
      had a stimulatory effect on the ligand-induced transcriptional activation by GR
      and also increased the steroid-sensitivity. Furthermore, DAP3 formed a complex
      with several other nuclear receptors and some basic helix-loop-helix/Per-Arnt-Sim
      proteins, as well as with heat-shock protein 90 (hsp90) (Arnt is the aryl
      hydrocarbon-receptor nuclear translocator, and Per and Sim are the Drosophila
      proteins Period and Single-minded). The results suggest that DAP3 could have an
      important role in GR action, possibly by modulating the cytoplasmic GR-hsp90
      complex. Since glucocorticoids can induce apoptosis, the pro-apoptotic DAP3
      protein may be involved in this function of GR.

PMID- 10903154
TI  - Expression of arginine kinase enzymatic activity and mRNA in gills of the
      euryhaline crabs Carcinus maenas and Callinectes sapidus.
AB  - Phosphagen kinases catalyze the reversible dephosphorylation of guanidino
      phosphagens such as phosphocreatine and phosphoarginine, contributing to the
      restoration of adenosine triphosphate concentrations in cells experiencing high
      and variable demands on their reserves of high-energy phosphates. The major
      invertebrate phosphagen kinase, arginine kinase, is expressed in the gills of two
      species of euryhaline crabs, the blue crab Callinectes sapidus and the shore crab
      Carcinus maenas, in which energy-requiring functions include monovalent ion
      transport, acid-base balance, nitrogen excretion and gas exchange. The enzymatic
      activity of arginine kinase approximately doubles in the ion-transporting gills
      of C. sapidus, a strong osmoregulator, when the crabs are transferred from high
      to low salinity, but does not change in C. maenas, a more modest osmoregulator.
      Amplification and sequencing of arginine kinase cDNA from both species,
      accomplished by reverse transcription of gill mRNA and the polymerase chain
      reaction, revealed an open reading frame coding for a 357-amino-acid protein. The
      predicted amino acid sequences showed a minimum of 75 % identity with arginine
      kinase sequences of other arthropods. Ten of the 11 amino acid residues believed
      to participate in arginine binding are completely conserved among the arthropod
      sequences analyzed. An estimation of arginine kinase mRNA abundance indicated
      that acclimation salinity has no effect on arginine kinase gene transcription.
      Thus, the observed enhancement of enzyme activity in C. sapidus probably results
      from altered translation rates or direct activation of pre-existing enzyme
      protein.

PMID- 10903155
TI  - Exploring dynamic similarity in human running using simulated reduced gravity.
AB  - The Froude number (a ratio of inertial to gravitational forces) predicts the
      occurrence of dynamic similarity in legged animals over a wide range of sizes and
      velocities for both walking and running gaits at Earth gravity. This is puzzling
      because the Froude number ignores elastic forces that are crucial for
      understanding running gaits. We used simulated reduced gravity as a tool for
      exploring dynamic similarity in human running. We simulated reduced gravity by
      applying a nearly constant upward force to the torsos of our subjects while they
      ran on a treadmill. We found that at equal Froude numbers, achieved through
      different combinations of velocity and levels of gravity, our subjects did not
      run in a dynamically similar manner. Thus, the inertial and gravitational forces
      that comprise the Froude number were not sufficient to characterize running in
      reduced gravity. Further, two dimensionless numbers that incorporate elastic
      forces, the Groucho number and the vertical Strouhal number, also failed to
      predict dynamic similarity in reduced-gravity running. To better understand the
      separate effects of velocity and gravity, we also studied running mechanics at
      fixed absolute velocities under different levels of gravity. The effects of
      velocity and gravity on the requirements of dynamic similarity differed in both
      magnitude and direction, indicating that there are no two velocity and gravity
      combinations at which humans will prefer to run in a dynamically similar manner.
      A comparison of walking and running results demonstrated that reduced gravity had
      different effects on the mechanics of each gait. This suggests that a single
      unifying hypothesis for the effects of size, velocity and gravity on both walking
      and running gaits will not be successful.

PMID- 10903156
TI  - Modulation of the cost of pHi regulation during metabolic depression: a (31)P-NMR
      study in invertebrate (Sipunculus nudus) isolated muscle.
AB  - Extracellular acidosis has been demonstrated to play a key role in the process of
      metabolic depression under long-term environmental stress, exemplified in the
      marine invertebrate Sipunculus nudus. These findings led to the hypothesis that
      acid-base regulation is associated with a visible cost depending on the rate and
      mode of H(+)-equivalent ion exchange. To test this hypothesis, the effects of
      different ion-transport inhibitors on the rate of pH recovery during hypercapnia,
      on energy turnover and on steady-state acid-base variables were studied in
      isolated body wall musculature of the marine worm Sipunculus nudus under control
      conditions (pHe 7.90) and during steady-state extracellular acidosis (pHe 7.50 or
      7.20) by in vivo (31)P-NMR and oxygen consumption analyses. During acute
      hypercapnia (2 % CO(2)), recovery of pHi was delayed at pHe 7.5 compared with pHe
      7.9. Inhibition of the Na(+)/H(+)-exchanger by 5-(N,N-dimethyl)-amiloride (DMA)
      at pHe 7.5 delayed recovery even further. This effect was much smaller at pHe
      7.9. Inhibition of anion exchange by the addition of the transport inhibitor 4,
      4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) prevented pH recovery at
      pHe 7.5 and delayed recovery at pHe 7.9, in accordance with an effect on Na(+)
      dependent Cl(-)/HCO(3)(-) exchange. The effects of ouabain, DIDS and DMA on
      metabolic rate were reduced at low pHe, thereby supporting the conclusion that
      acidosis caused the ATP demand of Na(+)/K(+)-ATPase to fall. This reduction
      occurred via an inhibiting effect on both Na(+)/H(+)- and Na(+)-dependent Cl(
      )/HCO(3)(-) (i.e. Na(+)/H(+)/Cl(-)/HCO(3)(-)) exchange in accordance with a
      reduction in the ATP demand for acid-base regulation during metabolic depression.
      Considering the ATP stoichiometries of the two exchangers, metabolic depression
      may be supported by the predominant use of Na(+)/H(+)/Cl(-)/HCO(3)(-) exchange
      under conditions of extracellular acidosis.

PMID- 10903157
TI  - The effect of alterations in activity and body temperature on the pulmonary
      surfactant system in the lesser long-eared bat Nyctophilus geoffroyi.
AB  - Pulmonary surfactant is a mixture of phospholipids, neutral lipids and proteins
      that controls the surface tension of the fluid lining the lung. It is critical
      for lung stability and function. The amount and composition of surfactant are
      influenced by physiological variables such as metabolic rate, body temperature
      and ventilation. We investigated the plasticity of the pulmonary surfactant
      system in the microchiropteran bat Nyctophilus geoffroyi throughout a natural 24
      h cycle. Bats were housed at 24 degrees C on a fixed (8 h:16 h) light:dark
      photoperiod. At 4 h intervals throughout the 24 h period, bats were lavaged and
      the surfactant analysed for absolute and relative amounts of total phospholipid
      (PL), disaturated phospholipid (DSP) and cholesterol (Chol). N. geoffroyi
      experienced two peaks of activity, at 18:00 h and 06:00 h. The amount of
      surfactant increased 1.5-fold upon arousal from torpor. The proportion of DSP to
      PL in the surfactant remained constant. Similarly, the Chol/PL and Chol/DSP
      ratios remained relatively constant. Surfactant cholesterol content did not
      increase during torpor in N. geoffroyi. Cholesterol does not appear to control
      surfactant fluidity during torpor in these bats, but instead the cholesterol
      content exactly mirrored the diurnal changes in body temperature.

PMID- 10903158
TI  - Patterns of cardiovascular and ventilatory response to elevated metabolic states
      in the lizard Varanus exanthematicus.
AB  - The principal function of the cardiopulmonary system is the precise matching of
      O(2) and CO(2) transport to the metabolic requirements of different tissues. In
      some ecothermic vertebrates (amphibians and reptiles), vdot (O2) increases
      dramatically following feeding. Factorial increments in vdot (O2) range from 1.7
      to 44 times above resting rates, and in some cases vdot (O2) approaches or even
      exceeds values measured during physical activity. There is virtually no
      information on the cardiopulmonary response during the postprandial period in
      these animals or how the pattern of cardiopulmonary support compares with that
      during activity. In our experiments, pulmonary ventilation ( vdot e), heart rate
      (fh), systemic blood flow ( qdot (sys)), rate of oxygen consumption ( vdot (O2))
      and rate of carbon dioxide production ( vdot (CO2)) were measured at 35 degrees C
      in the lizard Varanus exanthematicus for 24 h prior to the ingestion of meals of
      various sizes and measured continuously for up to 72 h during the postprandial
      period. The results of this study were compared with previously published values
      for treadmill exercise in the same experimental animals. The change in fh and
      stroke volume (V(S)) for a given increment in vdot (O2) did not differ during
      exercise and digestion. In contrast, the ventilatory response was very dependent
      on the nature of the elevated metabolic state. During digestion, an increase in
      vdot (O2) resulted in a relative hypoventilation in comparison with resting
      values, whereas hyperventilation characterized the response during activity.
      During exercise, breathing frequency (f) increased 10- to 40-fold above resting
      values accompanied by large reductions in tidal volume (V(T)). In contrast,
      postprandial increases in vdot (O2) resulted in relatively minor changes in f and
      V(T) almost doubled. These results indicate that, in these lizards, the cardiac
      response to elevated vdot (O2) is stereotyped, the response being predictable
      irrespective of the source of the metabolic increment. In contrast, the
      ventilatory response is flexible and state-dependent, not only in pattern but
      also in its frequency and volume components.

PMID- 10903159
TI  - Ventilatory and cardiovascular responses of a python (Python molurus) to exercise
      and digestion.
AB  - To investigate the potential limiting steps of peak metabolic rates, we examined
      gas exchange rates ( vdot (O2), vdot (CO2)), respiratory exchange ratio (RER),
      breathing frequency, tidal volume, minute ventilation volume (V.e) as well as the
      heart rate, systemic blood flow and stroke volume of Burmese pythons (Python
      molurus) while fasting at rest, exercising, digesting and exercising while
      digesting. All measured variables increased significantly during exercise
      (crawling at 0.4 km h(-)(1) and at vdot (O2max)), highlighted by a 17-fold
      increase in vdot (CO2) and a 24-fold increase in V.e. During the digestion of a
      meal equivalent to 25 % of the snake's body mass, pythons responded with
      increases in vdot (O2) and heart rate similar to those experienced during
      exercise, along with a 4.5-fold increase in systemic blood flow. Interestingly,
      pythons hyperventilated while exercising, whereas they hypoventilated during
      digestion. The combined demands of exercise and digestion resulted in
      significantly higher vdot (O2), vdot (CO2), breathing frequency and heart rate
      than during either exercise or digestion alone. Evidently, the capacities of the
      ventilatory and cardiovascular systems to transport oxygen to locomotor muscles
      are not a limiting factor in the attainment of peak metabolic rates during
      exercise in pythons

PMID- 10903160
TI  - Gastrointestinal uptake and distribution of copper in rainbow trout.
AB  - A single dose of radioactive copper ((64)Cu or new Cu) was infused into the
      stomach of rainbow trout (Oncorhynchus mykiss) to model dietary copper (Cu)
      uptake under conditions of a normal nutritional dose and optimum environmental
      temperature (16 degrees C, 0.117 microg Cu g(-)(1 )body mass). The distribution
      of new Cu to the gut and internal organs occurred in two phases: rapid uptake by
      the gut tissues (almost complete by 24 h post-infusion) followed by slower uptake
      by the internal organs. By 72 h, 60 % of the dose had been excreted, 19 % was
      still retained in the gut tissue, 10 % remained in the lumen and 12 % had been
      absorbed across the gut and partitioned amongst the internal organs. A reduction
      in water temperature of 10 degrees C (to 6 degrees C) significantly retarded
      components of new Cu distribution (movement of the bolus along the gut and
      excretion); nonetheless, by 72 h, the fraction absorbed by all the internal
      organs was similar to that at 16 degrees C. An increase in water temperature of 3
      degrees C (to 19 degrees C) caused a pronounced increase in internal organ uptake
      by 24 h to approximately double the uptake occurring at 16 degrees C. The uptake
      of new Cu by the gut tissue had a low temperature coefficient (Q(10)<1)
      consistent with simple diffusion, while the temperature coefficient for transfer
      of new Cu from gut tissue to the internal organs was high (Q(10)>2), consistent
      with facilitated transport. Internally, the liver and gall bladder (including
      bile) were the target organs for dietary Cu partitioning since they were the only
      organs that concentrated new Cu from the plasma. Individual tissues differed in
      terms of the exchange of their background Cu pools with new Cu. The background Cu
      in the walls of the gastrointestinal tract (excluding stomach) exchanged 45-94 %
      with new Cu from the gut lumen, while tissues such as the stomach, gills, kidney,
      carcass and fat had 5-7 % exchangeable background Cu. The liver, heart, spleen,
      ovary, bile and plasma had only 0.2-0.8 % exchangeable background Cu. The
      gastrointestinal tissues appear to act as a homeostatic organ, regulating the
      absorption of nutritional (non-toxic) doses of Cu (0. 117 microg g(-)(1 )body
      mass day(-)(1)) by the internal organs. Within the dose range we used and at
      optimal temperature (16 degrees C), the new Cu content of the gut tissues
      fluctuated, but absorption of new Cu by the internal organs remained relatively
      constant. For example, predosing the fish with non-radioactive Cu caused new Cu
      absorption by the gut tissues to double and decreased new Cu excretion from 38 to
      1.5 %, but had no effect on new Cu uptake by the internal organs. Feeding fish
      after application of the normal liquid dose of new Cu also had no effect on new
      Cu uptake by the internal organs, even though the presence of food in the
      digestive tract reduced the binding of new Cu to the gut tissues and assisted
      with the excretion of new Cu. The gut was therefore able to regulate new Cu
      internalization at this dosage. Higher new Cu doses (10, 100 and 1000 times the
      normal dose), however, evoked regurgitation and increased new Cu excretion within
      4 h of application but did not elevate new Cu levels in gut tissue beyond a
      threshold of approximately 40 microg of new Cu. Only at the highest dose (1000
      times the normal dose, 192 microg g(-)(1 )body mass), equivalent to toxic
      concentrations in the daily diet (7000 microg Cu g(-)(1 )dry mass food), was the
      buffering capacity of the gut overwhelmed, resulting in an increase in internal
      new Cu uptake.

PMID- 10903161
TI  - Broad oxygen tolerance in the nematode Caenorhabditis elegans.
AB  - This study examined the effects of oxygen tensions ranging from 0 to 90 kPa on
      the metabolic rate (rate of carbon dioxide production), movement and survivorship
      of the free-living soil nematode Caenorhabditis elegans. C. elegans requires
      oxygen to develop and survive. However, it can maintain a normal metabolic rate
      at oxygen levels of 3.6 kPa and has near-normal metabolic rates at oxygen levels
      as low as 2 kPa. The ability to withstand low ambient oxygen levels appears to be
      a consequence of the small body size of C. elegans, which allows diffusion to
      supply oxygen readily to the cells without requiring any specialized respiratory
      or metabolic adaptations. Thus, the small size of this organism pre-adapts C.
      elegans to living in soil environments that commonly become hypoxic. Movement in
      C. elegans appears to have a relatively minor metabolic cost. Several
      developmental stages of C. elegans were able to withstand up to 24 h of anoxia
      without major mortality. Longer periods of anoxia significantly increased
      mortality, particularly for eggs. Remarkably, long-term exposure to 100 % oxygen
      had no effect on the metabolic rate of C. elegans, and populations were able to
      survive for a least 50 generations in 100 % (90 kPa) oxygen. Such hyperoxic
      conditions are fatal to most organisms within a short period.

PMID- 10903162
TI  - Direct determination of the kinetics of oxygen diffusion to the photocytes of a
      bioluminescent elaterid larva, measurement of gas- and aqueous-phase diffusional
      barriers and modelling of oxygen supply.
AB  - We describe the development and use of a direct kinetic technique to determine
      the time taken for oxygen to diffuse from the external environment into the light
      producing cells (photocytes) in the prothorax of bioluminescent larvae of
      Pyrearinus termitilluminans. This was achieved by measuring the time course of
      the pseudoflash induced through sequential anoxia followed by normoxia. We have
      also determined the separate times taken for this oxygen diffusion in gaseous and
      tissue (predominantly aqueous) phases by using helium and nitrogen as the carrier
      gas. Of the total time taken for diffusion, that in the gas phase required 613+/
      136 ms (mean +/- s.e. m., N=5) whilst that in the aqueous phase required 1313+/
      187 ms. These values imply pathlengths of diffusion in the gaseous and aqueous
      phases of 4.80x10(-)(3)+/-0.53x10(-)(3) and 8. 89x10(-)(5)+/-0.61x10(-)(5 )m,
      respectively. In addition, the pathlength of gas-phase diffusion was used to
      derive a parameter relating to the tortuosity of the tracheal system. These
      values, together with those obtained upon bioluminescent oxygen consumption, have
      been used to model oxygen supply to the photocyte. From these studies, it would
      also appear that the modulation of tracheolar fluid levels might be a significant
      mechanism of control of tissue oxygen levels in at least some insects.

PMID- 10903164
TI  - Responses of anterior lateral line afferent neurones to water flow.
AB  - The mechanoreceptive lateral line system detects hydrodynamic stimuli and plays
      an important role in a number of types of fish behaviour, including orientation
      to water currents. The lateral line is composed of hair cell receptor organs
      called neuromasts that occur as superficial neuromasts on the surface of the skin
      or canal neuromasts located in subepidermal canals. Both are innervated by
      primary afferents of the lateral line nerves. Although there have been extensive
      studies of the response properties of lateral line afferents to vibrating
      sources, their response to water flow has not been reported. In this study, we
      recorded extracellularly from anterior lateral line afferents in the New Zealand
      long-fin eel Anguilla dieffenbachii while stimulating the eel with unidirectional
      water flows at 0.5-4 cm s(-)(1). Of the afferents, 80 % were flow-sensitive to
      varying degrees, the response magnitude increasing with flow rate. Flow-sensitive
      fibres gave non-adapting tonic responses, indicating that these fibres detect
      absolute flow velocity. Further studies are needed to confirm whether flow
      sensitive and flow-insensitive fibres correlate with superficial and canal
      neuromasts, respectively.

PMID- 10903163
TI  - Early specialization of the superfast myosin in extraocular and laryngeal
      muscles.
AB  - Extraocular muscle (EOM) exhibits high-velocity, low-tension contractions
      compared with other vertebrate striated muscles. These distinctive properties
      have been associated with a novel myosin heavy chain (MyHC) isoform, MyHC-EO. An
      atypical MyHC, MyHC IIL, has also been identified in laryngeal muscles that have
      similarly fast contractile properties. It co-migrates with MyHC-EO on high
      resolution SDS gels, but appeared to be encoded by a different mRNA. We combined
      CNBr peptide maps and full-length cDNA sequences to show that rabbit muscle EO
      and IIL MyHCs are identical. Analysis of the 5; untranslated region (5;UTR) of
      the mRNAs identified three variants that result from a combination of alternative
      splicing and multiple transcription initiation sites. This complex pattern of
      5;UTRs has not been reported previously for MyHC genes. We identified the human
      homologue of the MyHC-EO gene in GenBank, and analyzed the 5; upstream region,
      which revealed a paucity of muscle-specific transcription factor binding sites
      compared with the other MyHC genes. These features are likely to be critical to
      the unique regulation and tissue-specific expression of the MyHC-EO/IIL gene.
      Phylogenetic analysis indicates that MyHC-EO/IIL diverged from an ancestral MyHC
      gene to generate the first specialized fast myosin. The catalytic S1 head domain
      is more closely related to the fast MyHCs, while the rod is more closely related
      to the slow/cardiac MyHCs. The exon boundaries of the MyHC-EO are identical to
      those of the embryonic MyHC gene and virtually identical to those of the &agr;
      and (&bgr;) cardiac genes. This implies that most of the current exon boundaries
      were present in the ancestral gene, predating the duplications that generated the
      family of skeletal and cardiac myosin genes.

PMID- 10903165
TI  - Wolbachia infection and cytoplasmic incompatibility in the cricket Teleogryllus
      taiwanemma.
AB  - Wolbachia are cytoplasmically inherited bacteria found in many arthropods. They
      induce various reproductive alterations in their hosts, including cytoplasmic
      incompatibility, thelytokous parthenogenesis, feminization and male-killing. In
      this study, we examined Wolbachia infection and its effects on the host cricket
      Teleogryllus taiwanemma. In a phylogenetic study based on the wsp gene coding for
      a Wolbachia surface protein, the Wolbachia strain harboured by T. taiwanemma was
      clustered together with those harboured by Laodelphax striatellus, Tribolium
      confusum, Acraea encedon, Trichogramma deion and Adalia bipunctata. Crossing
      experiments using the Wolbachia-infected and uninfected strains of cricket showed
      that the infection is associated with the expression of unidirectional
      cytoplasmic incompatibility: the egg hatch rate in the incompatible cross between
      the infected males and uninfected females was 20.3 %. We also examined the
      distribution of Wolbachia within the host using polymerase chain reaction assays;
      they were detected in the antennae, heads, forewings, hindwings, testes, ovaries,
      Malpighian tubules, foot muscles and fat bodies. Quantitative polymerase chain
      reaction assays showed that the bacterial density was highest in the fat bodies,
      followed by the ovaries and testes. Wolbachia were not detected in the haemolymph
      or in mature spermatozoa. The spermatozoa of the infected male may be modified by
      the presence of Wolbachia during its development. To examine this possibility, we
      compared the profiles of sperm proteins between the infected and uninfected males
      using two-dimensional gel electrophoresis. However, no differences in the protein
      profiles were observed.

PMID- 10903166
TI  - Estimation of thermal constants: the importance of using equilibrium temperature
      rather than ambient temperature demonstrated with hoverflies (Diptera, Syrphidae,
      genus Eristalis).
AB  - Water evaporation has a marked effect on the passive rates of body temperature
      change of eristaline hoverflies. It results in the equilibrium temperature of
      these flies being significantly lower than ambient temperature. Different values
      for the cooling and warming constants are therefore obtained depending on whether
      equilibrium or ambient temperature is used as the baseline. Hence, care must be
      taken when estimating these constants with all animals, especially those of
      moderate to high permeability. It is recommended that equilibrium temperature be
      used in such situations. Evaporative cooling is probably also responsible for
      cooling constants being higher than warming constants in this and other studies.

PMID- 10903167
TI  - Axis-inducing activities and cell fates of the zebrafish organizer.
AB  - We have investigated axis-inducing activities and cellular fates of the zebrafish
      organizer using a new method of transplantation that allows the transfer of both
      deep and superficial organizer tissues. Previous studies have demonstrated that
      the zebrafish embryonic shield possesses classically defined dorsal organizer
      activity. When we remove the morphologically defined embryonic shield, embryos
      recover and are completely normal by 24 hours post-fertilization. We find that
      removal of the morphological shield does not remove all goosecoid- and floating
      head-expressing cells, suggesting that the morphological shield does not comprise
      the entire organizer region. Complete removal of the embryonic shield and
      adjacent marginal tissue, however, leads to a loss of both prechordal plate and
      notochord. In addition, these embryos are cyclopean, show a significant loss of
      floor plate and primary motorneurons and display disrupted somite patterning.
      Motivated by apparent discrepancies in the literature we sought to test the axis
      inducing activity of the embryonic shield. A previous study suggested that the
      shield is capable of only partial axis induction, specifically being unable to
      induce the most anterior neural tissues. Contrary to this study, we find shields
      can induce complete secondary axes when transplanted into host ventral germ-ring.
      In induced secondary axes donor tissue contributes to notochord, prechordal plate
      and floor plate. When explanted shields are divided into deep and superficial
      fragments and separately transplanted we find that deep tissue is able to induce
      the formation of ectopic axes with heads but lacking posterior tissues. We
      conclude that the deep tissue included in our transplants is important for proper
      head formation.

PMID- 10903168
TI  - Deletion of a silencer element disrupts H19 imprinting independently of a DNA
      methylation epigenetic switch.
AB  - The H19 imprinted gene is silenced when paternally inherited and active only when
      inherited maternally. This is thought to involve a cis-acting control region
      upstream of H19 that is responsible for regulating a number of functions
      including DNA methylation, asynchronous replication of parental chromosomes and
      an insulator. Here we report on the function of a 1.2 kb upstream element in the
      mouse, which was previously shown to function as a bi-directional silencer in
      Drosophila. The cre-loxP-mediated targeted deletion of the 1.2 kb region had no
      effect on the maternal allele. However, there was loss of silencing of the
      paternal allele in many endodermal and other tissues. The pattern of expression
      was very similar to the expression pattern conferred by the enhancer elements
      downstream of H19. We could not detect an effect on the expression of the
      neighbouring imprinted Igf2 gene, suggesting that the proposed boundary element
      insulating this gene from the downstream enhancers was unaffected. Despite
      derepression of the paternal H19 allele, the deletion surprisingly did not affect
      the differential DNA methylation of the locus, which displayed an appropriate
      epigenetic switch in the parental germlines. Furthermore, the characteristic
      asynchronous pattern of DNA replication at H19 was also not disrupted by the
      deletion, suggesting that the sequences that mediate this were also intact. The
      silencer is therefore part of a complex cis-regulatory region upstream of the H19
      gene and acts specifically to ensure the repression of the paternal allele,
      without a predominant effect on the epigenetic switch in the germline.

PMID- 10903169
TI  - Left-right asymmetry in C. elegans intestine organogenesis involves a LIN
      12/Notch signaling pathway.
AB  - The C. elegans intestine is a simple tube consisting of a monolayer of epithelial
      cells. During embryogenesis, cells in the anterior of the intestinal primordium
      undergo reproducible movements that lead to an invariant, asymmetrical 'twist' in
      the intestine. We have analyzed the development of twist to determine how left
      right and anterior-posterior asymmetries are generated within the intestinal
      primordium. The twist requires the LIN-12/Notch-like signaling pathway of C.
      elegans. All cells within the intestinal primordium initially express LIN-12, a
      receptor related to Notch; however, only cells in the left half of the primordium
      contact external, nonintestinal cells that express LAG-2, a ligand related to
      delta. LIN-12 and LAG-2 mediated interactions result in the left primordial cells
      expressing lower levels of LIN-12 than the right primordial cells. We propose
      that this asymmetrical pattern of LIN-12 expression is the basis for asymmetry in
      later cell-cell interactions within the primordium that lead directly to
      intestinal twist. Like the interactions that initially establish LIN-12
      asymmetry, the later interactions are mediated by LIN-12. The later interactions,
      however, involve a different ligand related to delta, called APX-1. We show that
      the anterior-posterior asymmetry in intestinal twist involves the kinase LIT-1,
      which is part of a signaling pathway in early embryogenesis that generates
      anterior-posterior differences between sister cells.

PMID- 10903170
TI  - The enhancer of split complex of Drosophila includes four Notch-regulated members
      of the bearded gene family.
AB  - During Drosophila development, transcriptional activation of genes of the
      Enhancer of split Complex (E(spl)-C) is a major response to cell-cell signaling
      via the Notch (N) receptor. Although the structure and function of the E(spl)-C
      have been studied intensively during the past decade, these efforts have focused
      heavily on seven transcription units that encode basic helix-loop-helix (bHLH)
      repressors; the non-bHLH members of the complex have received comparatively
      little attention. In this report, we analyze the structure, regulation and
      activity of the m1, m2 and m6 genes of the E(spl)-C. We find that E(spl)m2 and
      E(spl)m6 encode divergent members of the Bearded (Brd) family of proteins,
      bringing to four (m(alpha), m2, m4 and m6) the number of Brd family genes in the
      E(spl)-C. We demonstrate that the expression of both m2 and m6 is responsive to N
      receptor activity and that both genes are apparently direct targets of regulation
      by the N-activated transcription factor Suppressor of Hairless. Consistent with
      this, both are expressed specifically in multiple settings where N signaling
      takes place. Particularly noteworthy is our finding that m6 transcripts
      accumulate both in adult muscle founder cells in the embryo and in a subset of
      adepithelial (muscle precursor) cells associated with the wing imaginal disc. We
      show that overexpression of either m2 or m6 interferes with N-dependent cell fate
      decisions in adult PNS development. Surprisingly, while misexpression of m6
      impairs lateral inhibition, overexpression of m2 potentiates it, suggesting
      functional diversification within the Brd protein family. Finally, we present our
      initial studies of the structure, expression and regulation of the newest member
      of the Brd gene family, Ocho, which is located in the recently identified Bearded
      Complex.

PMID- 10903171
TI  - Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice
      implicates a novel mesenchymal structure with putative instructive properties in
      villus morphogenesis.
AB  - Development of the gastrointestinal (GI) tract depends on reciprocal epithelial
      mesenchymal cell signaling. Here, we demonstrate a role for platelet-derived
      growth factor-A (PDGF-A) and its receptor, PDGFR-(alpha), in this process. Mice
      lacking PDGF-A or PDGFR-(alpha) were found to develop an abnormal GI mucosal
      lining, including fewer and misshapen villi and loss of pericryptal mesenchyme.
      Onset of villus morphogenesis correlated with the formation of clusters of PDGFR
      (alpha) positive cells, 'villus clusters', which remained located at the tip of
      the mesenchymal core of the growing villus. Lack of PDGF-A or PDGFR-(alpha)
      resulted in progressive depletion of PDGFR-(alpha) positive mesenchymal cells,
      the formation of fewer villus clusters, and premature expression of smooth muscle
      actin (SMA) in the villus mesenchyme. We found that the villus clusters were
      postmitotic, expressed BMP-2 and BMP-4, and that their formation correlated with
      downregulated DNA synthesis in adjacent intestinal epithelium. We propose a model
      in which villus morphogenesis is initiated as a result of aggregation of PDGFR
      (&agr;) positive cells into cell clusters that subsequently function as
      mesenchymal centers of signaling to the epithelium. The role of PDGF-A seems to
      be to secure renewal of PDGFR-(alpha) positive cells when they are consumed in
      the initial rounds of cluster formation.

PMID- 10903172
TI  - Animal and vegetal poles of the mouse egg predict the polarity of the embryonic
      axis, yet are nonessential for development.
AB  - Recent studies suggest early (preimplantation) events might be important in the
      development of polarity in mammalian embryos. We report here lineage tracing
      experiments with green fluorescent protein showing that cells located either near
      to or opposite the polar body at the 8-cell stage of the mouse embryo retain
      their same relative positions in the blastocyst. Thus they come to lie on either
      end of an axis of symmetry of the blastocyst that has recently been shown to
      correlate with the anterior-posterior axis of the postimplantation embryo (see R.
      J. Weber, R. A. Pedersen, F. Wianny, M. J. Evans and M. Zernicka-Goetz (1999).
      Development 126, 5591-5598). The embryonic axes of the mouse can therefore be
      related to the position of the polar body at the 8-cell stage, and by
      implication, to the animal-vegetal axis of the zygote. However, we also show that
      chimeric embryos constructed from 2-cell stage blastomeres from which the animal
      or the vegetal poles have been removed can develop into normal blastocysts and
      become fertile adult mice. This is also true of chimeras composed of animal or
      vegetal pole cells derived through normal cleavage to the 8-cell stage. We
      discuss that although polarity of the postimplantation embryo can be traced back
      to the 8-cell stage and in turn to the organisation of the egg, it is not
      absolutely fixed by this time.

PMID- 10903173
TI  - Early development of the Drosophila mushroom body: the roles of eyeless and
      dachshund.
AB  - The mushroom body (MB) is a uniquely identifiable brain structure present in most
      arthropods. Functional studies have established its role in learning and memory.
      Here we describe the early embryonic origin of the four neuroblasts that give
      rise to the mushroom body and follow its morphogenesis through later embryonic
      stages. In the late embryo, axons of MB neurons lay down a characteristic pattern
      of pathways. eyeless (ey) and dachshund (dac) are expressed in the progenitor
      cells and neurons of the MB in the embryo and larva. In the larval brains of the
      hypomorphic ey(R) strain, we find that beside an overall reduction of MB neurons,
      one MB pathway, the medial lobe, is malformed or missing. Overexpression of
      eyeless in MBs under the control of an MB-specific promoter results in a converse
      type of axon pathway abnormality, i.e. malformation or loss of the dorsal lobe.
      In contrast, loss of dachshund results in deformation of the dorsal lobe, whereas
      no lobe abnormalities can be detected following dachshund overexpression. These
      results indicate that ey and dachshund may have a role in axon pathway selection
      during embryogenesis.

PMID- 10903175
TI  - Loss of connexin45 causes a cushion defect in early cardiogenesis.
AB  - At around embryonic day 9, the primitive heart of a mouse embryo undergoes
      spectacular alterations within 24 hours. We created mice harboring an nls-lacZ
      gene in place of connexin45, which encodes the only known gap junction protein in
      the primitive heart before embryonic day 9, using the Cre-loxP system. Connexin45
      deficient mice died of heart failure at around embryonic day 10. They initiated
      heart contractions, but conduction block appeared within 24 hours after the first
      contractions. Their cardiac walls displayed an endocardial cushion defect, while
      the cardiac jelly was present. These abnormalities were caused by impairment of
      the epithelial-mesenchymal transformation of the cardiac endothelium. Activation
      of the cardiac endothelium depended on the presence of the connexin45 gap
      junctions since signaling through Ca(2+)/calcineurin and NF-ATc1 (originally
      named NF-ATc) was disrupted in the mutant hearts. These results indicate a
      requirement for gap junction channels during early cardiogenesis and hence
      implicate connexin45 in congenital heart diseases. http://www.
      biologists.com/Development/movies/dev4369.html

PMID- 10903174
TI  - Competence, specification and commitment in otic placode induction.
AB  - The inner ear is induced from cranial ectoderm adjacent to the hindbrain. Despite
      almost a century of study, the molecular mechanisms of inner ear induction remain
      obscure. We have identified four genes expressed very early in the anlage of the
      inner ear, the otic placode. Pax-2, Sox-3, BMP-7 and Notch are all expressed in
      placodal ectoderm from the 4-5 somite stage (ss) onwards, well before the otic
      placode becomes morphologically visible at the 12-14ss. We have used these four
      molecular markers to show that cranial ectoderm becomes specified to form the
      otic placode at the 4-6ss, and that this ectoderm is committed to a placodal fate
      by the 10ss. We also demonstrate that much of the embryonic ectoderm is competent
      to generate an otic placode if taken at a sufficiently early age. We have mapped
      the location of otic placode-inducing activity along the rostrocaudal axis of the
      embryo, and have determined that this activity persists at least until the 10ss.
      Use of the four molecular otic placode markers suggests that induction of the
      otic placode in birds occurs earlier than previously thought, and proceeds in a
      series of steps that are independently regulated.

PMID- 10903176
TI  - Mechanism of glia-neuron cell-fate switch in the Drosophila thoracic neuroblast 6
      4 lineage.
AB  - During development of the Drosophila central nervous system, neuroblast 6-4 in
      the thoracic segment (NB6-4T) divides asymmetrically into a medially located
      glial precursor cell and a laterally located neuronal precursor cell. In this
      study, to understand the molecular basis for this glia-neuron cell-fate decision,
      we examined the effects of some known mutations on the NB6-4T lineage. First, we
      found that prospero (pros) mutations led to a loss of expression of Glial cells
      missing, which is essential to trigger glial differentiation, in the NB6-4T
      lineage. In wild-type embryos, Pros protein was localized at the medial cell
      cortex of dividing NB6-4T and segregated to the nucleus of the glial precursor
      cell. miranda and inscuteable mutations altered the behavior of Pros, resulting
      in failure to correctly switch the glial and neuronal fates. Our results
      suggested that NB6-4T used the same molecular machinery in the asymmetric cell
      division as other neuroblasts in cell divisions producing ganglion mother cells.
      Furthermore, we showed that outside the NB6-4T lineage most glial cells appeared
      independently of Pros.

PMID- 10903177
TI  - In vivo induction of cardiac Purkinje fiber differentiation by coexpression of
      preproendothelin-1 and endothelin converting enzyme-1.
AB  - The rhythmic heart beat is coordinated by electrical impulses transmitted from
      Purkinje fibers of the cardiac conduction system. During embryogenesis, the
      impulse-conducting cells differentiate from cardiac myocytes in direct
      association with the developing endocardium and coronary arteries, but not with
      the venous system. This conversion of myocytes into Purkinje fibers requires a
      paracrine interaction with blood vessels in vivo, and can be induced in vitro by
      exposing embryonic myocytes to endothelin-1 (ET-1), an endothelial cell
      associated paracrine factor. These results suggest that an endothelial cell
      derived signal is capable of inducing juxtaposed myocytes to differentiate into
      Purkinje fibers. It remains unexplained how Purkinje fiber recruitment is
      restricted to subendocardial and periarterial sites but not those juxtaposed to
      veins. Here we show that while the ET-receptor is expressed throughout the
      embryonic myocardium, introduction of the ET-1 precursor (preproET-1) in the
      embryonic myocardium is not sufficient to induce myocytes to differentiate into
      conducting cells. ET converting enzyme-1 (ECE-1), however, is expressed
      preferentially in endothelial cells of the endocardium and coronary arteries
      where Purkinje fiber recruitment takes place. Retroviral-mediated coexpression of
      both preproET-1 and ECE-1 in the embryonic myocardium induces myocytes to express
      Purkinje fiber markers ectopically and precociously. These results suggest that
      expression of ECE-1 plays a key role in defining an active site of ET signaling
      in the heart, thereby determining the timing and location of Purkinje fiber
      differentiation within the embryonic myocardium.

PMID- 10903178
TI  - Expression of neurogenin3 reveals an islet cell precursor population in the
      pancreas.
AB  - Differentiation of early gut endoderm cells into the endocrine cells forming the
      pancreatic islets of Langerhans depends on a cascade of gene activation events
      controlled by transcription factors including the basic helix-loop-helix (bHLH)
      proteins. To delineate this cascade, we began by establishing the position of
      neurogenin3, a bHLH factor found in the pancreas during fetal development. We
      detect neurogenin3 immunoreactivity transiently in scattered ductal cells in the
      fetal mouse pancreas, peaking at embryonic day 15.5. Although not detected in
      cells expressing islet hormones or the islet transcription factors Isl1, Brn4,
      Pax6 or PDX1, neurogenin3 is detected along with early islet differentiation
      factors Nkx6.1 and Nkx2.2, establishing that it is expressed in immature cells in
      the islet lineage. Analysis of transcription factor-deficient mice demonstrates
      that neurogenin3 expression is not dependent on neuroD1/BETA2, Mash1, Nkx2.2,
      Nkx6.1, or Pax6. Furthermore, early expression of neurogenin3 under control of
      the Pdx1 promoter is alone sufficient to drive early and ectopic differentiation
      of islet cells, a capability shared by the pancreatic bHLH factor, neuroD1/BETA2,
      but not by the muscle bHLH factor, MyoD. However, the islet cells produced in
      these transgenic experiments are overwhelmingly (alpha) cells, suggesting that
      factors other than the bHLH factors are required to deviate from a default * cell
      fate. These data support a model in which neurogenin3 acts upstream of other
      islet differentiation factors, initiating the differentiation of endocrine cells,
      but switching off prior to final differentiation. The ability to uniquely
      identify islet cell precursors by neurogenin3 expression allows us to determine
      the position of other islet transcription factors in the differentiation cascade
      and to propose a map for the islet cell differentiation pathway.

PMID- 10903179
TI  - Ecdysteroid coordinates optic lobe neurogenesis via a nitric oxide signaling
      pathway.
AB  - Proliferation of neural precursors in the optic lobe of Manduca sexta is
      controlled by circulating steroids and by local production of nitric oxide (NO).
      Diaphorase staining, anti-NO synthase (NOS) immunocytochemistry and the NO
      indicator, DAF-2, show that cells throughout the optic anlage contain NOS and
      produce NO. Signaling via NO inhibits proliferation in the anlage. When exposed
      to low levels of ecdysteroid, NO production is stimulated and proliferation
      ceases. When steroid levels are increased, NO production begins to decrease
      within 15 minutes independent of RNA or protein synthesis and cells rapidly
      resume proliferation. Resumption of proliferation is not due simply to the
      removal of NO repression though, but also requires an ecdysteroid stimulatory
      pathway. The consequence of these opposing pathways is a sharpening of the
      responsiveness to the steroid, thereby facilitating a tight coordination between
      development of the different elements of the adult visual system.

PMID- 10903180
TI  - Two different activities of Suppressor of Hairless during wing development in
      Drosophila.
AB  - The Notch pathway plays a crucial and universal role in the assignation of cell
      fates during development. In Drosophila, Notch is a transmembrane protein that
      acts as a receptor of two ligands Serrate and delta. The current model of Notch
      signal transduction proposes that Notch is activated upon binding its ligands and
      that this leads to the cleavage and release of its intracellular domain (also
      called Nintra). Nintra translocates to the nucleus where it forms a dimeric
      transcription activator with the Su(H) protein. In contrast with this activation
      model, experiments with the vertebrate homologue of Su(H), CBF1, suggest that, in
      vertebrates, Nintra converts CBF1 from a repressor into an activator. Here we
      have assessed the role of Su(H) in Notch signalling during the development of the
      wing of Drosophila. Our results show that, during this process, Su(H) can
      activate the expression of some Notch target genes and that it can do so without
      the activation of the Notch pathway or the presence of Nintra. In contrast, the
      activation of other Notch target genes requires both Su(H) and Nintra, and, in
      the absence of Nintra, Su(H) acts as a repressor. We also find that the Hairless
      protein interacts with Notch signalling during wing development and inhibits the
      activity of Su(H). Our results suggest that, in Drosophila, the activation of
      Su(H) by Notch involve the release of Su(H) from an inhibitory complex, which
      contains the Hairless protein. After its release Su(H) can activate gene
      expression in absence of Nintra.

PMID- 10903181
TI  - Multiple pathways in the midline regulate concordant brain, heart and gut left
      right asymmetry.
AB  - The embryonic midline in vertebrates has been implicated in left-right
      development, but the mechanisms by which it regulates left-right asymmetric gene
      expression and organ morphogenesis are unknown. Zebrafish embryos have three
      domains of left-right asymmetric gene expression that are useful predictors of
      organ situs. cyclops (nodal), lefty1 and pitx2 are expressed in the left
      diencephalon; cyclops, lefty2 and pitx2 are expressed in the left heart field;
      and cyclops and pitx2 are expressed in the left gut primordium. Distinct
      alterations of these expression patterns in zebrafish midline mutants identify
      four phenotypic classes that have different degrees of discordance among the
      brain, heart and gut. These classes help identify two midline domains and several
      genetic pathways that regulate left-right development. A cyclops-dependent
      midline domain, associated with the prechordal plate, regulates brain asymmetry
      but is dispensable for normal heart and gut left-right development. A second
      midline domain, associated with the anterior notochord, is dependent on no tail,
      floating head and momo function and is essential for restricting asymmetric gene
      expression to the left side. Mutants in spadetail or chordino give discordant
      gene expression among the brain, heart and gut. one-eyed pinhead and schmalspur
      are necessary for asymmetric gene expression and may mediate signaling from
      midline domains to lateral tissues. The different phenotypic classes help clarify
      the apparent disparity of mechanisms proposed to explain left-right development
      in different vertebrates.

PMID- 10903182
TI  - Signaling and transcriptional regulation in early mammalian eye development: a
      link between FGF and MITF.
AB  - During vertebrate eye development, the optic vesicle is partitioned into a domain
      at its distal tip that will give rise to the neuroretina, and another at its
      proximal base that will give rise to the pigmented epithelium. Both domains are
      initially bipotential, each capable of giving rise to either neuroretina or
      pigmented epithelium. The partitioning depends on extrinsic signals, notably
      fibroblast growth factors, which emanate from the overlying surface ectoderm and
      induce the adjacent neuroepithelium to assume the neuroretinal fate. Using
      explant cultures of mouse optic vesicles, we demonstrate that bipotentiality of
      the optic neuroepithelium is associated with the initial coexpression of the
      basic-helix-loop-helix-zipper transcription factor MITF, which is later needed
      solely in the pigmented epithelium, and a set of distinct transcription factors
      that become restricted to the neuroretina. Implantation of fibroblast growth
      factor-coated beads close to the base of the optic vesicle leads to a rapid
      downregulation of MITF and the development of an epithelium that, by morphology,
      gene expression, and lack of pigmentation, resembles the future neuroretina.
      Conversely, the removal of the surface ectoderm results in the maintenance of
      MITF in the distal optic epithelium, lack of expression of the neuroretinal
      specific CHX10 transcription factor, and conversion of this epithelium into a
      pigmented monolayer. This phenomenon can be prevented by the application of
      fibroblast growth factor alone. In Mitf mutant embryos, parts of the future
      pigment epithelium become thickened, lose expression of a number of pigment
      epithelium transcription factors, gain expression of neuroretinal transcription
      factors, and eventually transdifferentiate into a laminated second retina. The
      results support the view that the bipotential optic neuroepithelium is
      characterized by overlapping gene expression patterns and that selective gene
      repression, brought about by local extrinsic signals, leads to the separation
      into discrete expression domains and, hence, to domain specification.

PMID- 10903183
TI  - p57(Kip2) regulates progenitor cell proliferation and amacrine interneuron
      development in the mouse retina.
AB  - A precise balance between proliferation and differentiation must be maintained
      during retinal development to obtain the correct proportion of each of the seven
      cell types found in the adult tissue. Cyclin kinase inhibitors can regulate cell
      cycle exit coincident with induction of differentiation programs during
      development. We have found that the p57(Kip2) cyclin kinase inhibitor is
      upregulated during G(1)/G(0) in a subset of retinal progenitor cells exiting the
      cell cycle between embryonic day 14.5 and 16.5 of mouse development. Retroviral
      mediated overexpression of p57(Kip2) in embryonic retinal progenitor cells led to
      premature cell cycle exit. Retinae from mice lacking p57(Kip2) exhibited
      inappropriate S-phase entry and apoptotic nuclei were found in the region where
      p57(Kip2) is normally expressed. Apoptosis precisely compensated for the
      inappropriate proliferation in the p57(Kip2)-deficient retinae to preserve the
      correct proportion of the major retinal cell types. Postnatally, p57(Kip2) was
      found to be expressed in a novel subpopulation of amacrine interneurons. At this
      stage, p57(Kip2 )did not regulate proliferation. However, perhaps reflecting its
      role during this late stage of development, animals lacking p57(Kip2) showed an
      alteration in amacrine subpopulations. p57(Kip2) is the first gene to be
      implicated as a regulator of amacrine subtype/subpopulation development.
      Consequently, we propose that p57(Kip2) has two roles during retinal development,
      acting first as a cyclin kinase inhibitor in mitotic progenitor cells, and then
      playing a distinct role in neuronal differentiation.

PMID- 10903184
TI  - The canonical Wg and JNK signaling cascades collaborate to promote both dorsal
      closure and ventral patterning.
AB  - Elaboration of the Drosophila body plan depends on a series of cell-identity
      decisions and morphogenetic movements regulated by intercellular signals. For
      example, Jun N-terminal kinase signaling regulates cell fate decisions and
      morphogenesis during dorsal closure, while Wingless signaling regulates segmental
      patterning of the larval cuticle via Armadillo. wingless or armadillo mutant
      embryos secrete a lawn of ventral denticles; armadillo mutants also exhibit
      dorsal closure defects. We found that mutations in puckered, a phosphatase that
      antagonizes Jun N-terminal kinase, suppress in a dose-sensitive manner both the
      dorsal and ventral armadillo cuticle defects. Furthermore, we found that
      activation of the Jun N-terminal kinase signaling pathway suppresses armadillo
      associated defects. Jun N-terminal kinase signaling promotes dorsal closure, in
      part, by regulating decapentaplegic expression in the dorsal epidermis. We
      demonstrate that Wingless signaling is also required to activate decapentaplegic
      expression and to coordinate cell shape changes during dorsal closure. Together,
      these results demonstrate that MAP-Kinase and Wingless signaling cooperate in
      both the dorsal and ventral epidermis, and suggest that Wingless may activate
      both the Wingless and the Jun N-terminal kinase signaling cascades.

PMID- 10903185
TI  - Jun mediates Frizzled-induced R3/R4 cell fate distinction and planar polarity
      determination in the Drosophila eye.
AB  - Jun acts as a signal-regulated transcription factor in many cellular decisions,
      ranging from stress response to proliferation control and cell fate induction.
      Genetic interaction studies have suggested that Jun and JNK signaling are
      involved in Frizzled (Fz)-mediated planar polarity generation in the Drosophila
      eye. However, simple loss-of-function analysis of JNK signaling components did
      not show comparable planar polarity defects. To address the role of Jun and JNK
      in Fz signaling, we have used a combination of loss- and gain-of-function
      studies. Like Fz, Jun affects the bias between the R3/R4 photoreceptor pair that
      is critical for ommatidial polarity establishment. Detailed analysis of jun(-)
      clones reveals defects in R3 induction and planar polarity determination, whereas
      gain of Jun function induces the R3 fate and associated polarity phenotypes. We
      find also that affecting the levels of JNK signaling by either reduction or
      overexpression leads to planar polarity defects. Similarly, hypomorphic allelic
      combinations and overexpression of the negative JNK regulator Puckered causes
      planar polarity eye phenotypes, establishing that JNK acts in planar polarity
      signaling. The observation that Dl transcription in the early R3/R4 precursor
      cells is deregulated by Jun or Hep/JNKK activation, reminiscent of the effects
      seen with Fz overexpression, suggests that Jun is one of the transcription
      factors that mediates the effects of fz in planar polarity generation.

PMID- 10903187
TI  - Surfactant protein SP-B counteracts inhibition of pulmonary surfactant by serum
      proteins.
AB  - In addition to the primary surfactant deficiency in newborns with respiratory
      distress syndrome (RDS), in the later course of RDS substantial protein leakage
      into the alveolar spaces can occur by damage to the alveolocapillary membrane.
      Acute lung injury results in surfactant dysfunction due in part to inhibition by
      serum proteins. The aim of this study was to investigate the influence of SP-B on
      the inhibitory effects of albumin (alb) and fibrinogen (fib) on the surface
      activity of pulmonary surfactant, using a) surface tension measurement with the
      pulsating bubble surfactometer in suspensions and b) in surfactant films applying
      the hypophase exchanger. After hypophase exchange a preformed film of Survanta is
      very resistant to the inhibitory activity of alb or fib. The surface tensions of
      suspensions are significantly higher (p <0.001) than the surface tensions of
      preformed surfactant films if alb or fib were added, e.g., 42 (41 to 43) mN/m vs.
      21 (19 to 22) mN/m for Survanta with 20 mg alb/ml. After additional
      supplementation of Survanta with SP-B the surface activity of Survanta/1% SP-B
      films did not show inhibition by fib (2 mg/ml), (surface tension 8 (4 to 13)
      mN/m). These results indicate that SP-B can play an important role to protect the
      pulmonary surfactant film from inactivation by serum proteins.

PMID- 10903186
TI  - sog and dpp exert opposing maternal functions to modify toll signaling and
      pattern the dorsoventral axis of the Drosophila embryo.
AB  - The short gastrulation (sog) and decapentaplegic (dpp) genes function
      antagonistically in the early Drosophila zygote to pattern the dorsoventral (DV)
      axis of the embryo. This interplay between sog and dpp determines the extent of
      the neuroectoderm and subdivides the dorsal ectoderm into two territories. Here,
      we present evidence that sog and dpp also play opposing roles during oogenesis in
      patterning the DV axis of the embryo. We show that maternally produced Dpp
      increases levels of the I(kappa)B-related protein Cactus and reduces the
      magnitude of the nuclear concentration gradient of the NF(kappa)B-related Dorsal
      protein, and that Sog limits this effect. We present evidence suggesting that Dpp
      signaling increases Cactus levels by reducing a signal-independent component of
      Cactus degradation. Epistasis experiments reveal that sog and dpp act downstream
      of, or in parallel to, the Toll receptor to reduce translocation of Dorsal
      protein into the nucleus. These results broaden the role previously defined for
      sog and dpp in establishing the embryonic DV axis and reveal a novel form of
      crossregulation between the NF(kappa)B and TGF(beta) signaling pathways in
      pattern formation.

PMID- 10903188
TI  - Immunological surrogate parameters in a prognostic model for multi-organ failure
      and death.
AB  - OBJECTIVE: To assess the ability of clinical or biochemical parameters to predict
      outcome (survival or non-survival; severe or moderate/no complication) using
      multiple regression analyses. DESIGN: Prospective, descriptive cohort study with
      no interventions SETTING: 12 surgical intensive care units of university
      hospitals and large community hospitals; four medical school research
      laboratories in eight European countries PATIENTS: 128 surgical patients with
      major intra-abdominal surgery admitted for at least two days to an intensive care
      unit MAIN OUTCOME MEASURES: Prediction of complications or survival based on
      analysis of clinical (Multiple Organ Dysfunction Score, Multi-Organ-Failure
      Score, Acute Physiology and Chronic Health Evaluation II scores) and
      immunological (plasma levels of endotoxin, endotoxin neutralizing capacity, IL-6,
      IL-8, cell associated IL-8, Fc-receptor polymorphism, soluble CD-14) parameters,
      with comparison of predicted and actual outcomes. RESULTS: APACHE II, MODS score,
      MOF score, platelets, IL-6, IL-8, ENC, cell ass. IL-8 were significantly
      different between survivors and non-survivors and patients with/without severe
      complications by univariate analysis. By multivariate analysis only MOF, MODS
      score, IL-6, platelets, comorbidity predicted complications with a sensitivity of
      82% and a specificity of 87%. Multivariate analysis demonstrated that only APACHE
      II score, plasma IL-8 and complications predicted death (sensitivity 84%;
      specificity 90%). CONCLUSION: Immunological surrogate parameters may predict
      complications and death of surgical ICU patients. The use of several parameters
      may add to increase sensitivity and specificity in a prognostic model.

PMID- 10903190
TI  - Late intra-arterial thrombolysis.
AB  - A 70-year-old woman with a progressive dominant hemisphere syndrome but only mild
      hemiparesis and a normal brain scan (>3 hours from stroke onset) showed
      angiographic occlusion of the left anterior cerebral artery and the middle
      cerebral artery at its trifurcation with preservation of the rolandic artery.
      Intra-arterial thrombolysis was started >6 hours from onset of symptoms.
      Recanalization occurred and the patient recovered with a transcortical motor
      aphasia and no motor deficit. A negative brain scan and an incomplete large
      hemispheric syndrome may indicate an extended time-window for intra-arterial
      thrombolysis.

PMID- 10903189
TI  - Macroangiopathy of the upper extremities in progressive systemic sclerosis.
AB  - BACKGROUND: Raynaud's phenomenon is a hallmark of progressive systemic sclerosis
      (SSc). While nailfold capillary changes are well known, morphological changes in
      larger arteries have less been focused on. OBJECTIVE AND METHODS: In the study
      presented we examined how often in digital subtraction angiography organic
      changes of the arteries of the fingers, hands and forearms were observed, whether
      they showed a typical picture like the changes in nailfold capillaries and
      whether they correlated with cutaneous sclerosis, Raynaud's phenomenon and
      serological findings. 29 patients were examined, 14 with acroscleroderma and 15
      with proximal ascending sclerosis. RESULTS: In 27 of those 29 patients a stenosis
      of the arteries of the upper extremity was found. The frequency of arterial
      occlusions decreased from the fingers (26 patients) to the forearms (9 patients
      with occlusion of the ulnar artery, none with occlusion of the radial artery).
      The arteries of 47% of patients with proximal ascending sclerosis showed no
      reactivity towards the alpha-sympatholyticum tolazoline hydrochloride due to
      severe organic changes while in patients with acroscleroderma only 14% of
      patients did not respond to tolazoline hydrochloride. The severity of Raynaud's
      phenomenon did not correlate with the severity of the angiographic findings. In
      patients with stenoses refractory to tolazoline hydrochloride and in those with
      occlusions Scl-70 autoantibodies were more frequently positive than in other
      patients with SSc (44% compared to 23%). CONCLUSION: As in SSc the severity of
      the organic arterial changes is in close correlation with the extent of the
      cutaneous sclerosis and with the serological findings the arterial system should
      gain much more importance in the diagnosis and therapy of SSc.

PMID- 10903191
TI  - Prader-Labhart-Willi syndrome: auxological response to a conventional dose of
      growth hormone in patients with classical growth hormone deficiency.
AB  - The aim of the study was to evaluate the effect of growth hormone (GH) (14
      IU/m2/week) on height, body mass index and predicted adult height in children
      with Prader-Labhart-Willi (PLWS) syndrome and GH deficiency. - By auxological
      criteria GH deficiency was suspected in 10 patients (age: 7-16 years). In 9
      patients two GH provocative testings and MR imaging of the pituitary were
      performed. IGF-I measurements, bone age determinations, body mass index (BMI),
      height standard deviation score, height velocity -SDS and predicted adult height
      (PAH) were determined before and during GH treatment. Nine patients could be
      followed for up to 2 years, 3 patients for 4 years and 2 patients for 5 years of
      GH treatment. - Predicted adult height could be calculated in all after 1 year of
      treatment and was on average 11.6 cm below target height (-17.6 to +2.5 cm). GH
      treatment in a conventional dose (14 IU/m2/week) in daily subcutaneous injections
      was performed. Height SDS improved from -3.47 to -2.27 after 2 years of
      treatment, height velocity SDS from -1.74 to +2.65 after 1 year and remained
      +1.78 after 2 years. PAH increased on average by 5.1 cm. BMI was unchanged during
      2 years. Bone age development was appropriate with +2.13 years after 2 years. In
      2 patients who were treated with GH for up to 5 years and in 1 who was treated up
      to 4 years, the positive effect on height SDS and height velocity SDS persisted. 
      In conclusion GH treatment in a conventional dose (14 IU/m2/week) in PLWS
      patients with GH deficiency is effective over a period of 2 years in regard to
      height development and predicted adult height but ony limited in regard to
      changes in BMI.

PMID- 10903192
TI  - Hodgkin's disease related Kaposi's sarcoma in a non HIV infected male patient: a
      case report and review of the literature on a rare condition.
AB  - A higher incidence of coexisting lymphoproliferative disease and Kaposi's sarcoma
      (KS) has been reported. However, the association of Hodgkin's disease (HD) and KS
      is a rare condition, and only 41 cases have been found upon a literature review
      of the last 33 years. In this study the case of a 70 year-old male patient with
      consecutive appearance of Hodgkin's disease (HD) and Kaposi's sarcoma (KS)
      without evidence of HIV infection or other immunodeficiency is presented. The
      data suggest, that the association of KS with HD may be due to common pathogenic
      mechanisms, rather than a direct causal relationship, except the requirement of
      an impaired immune system for the development of KS. Recently development of HD
      and KS has been associated with EBV and HHV-8, respectively. Neither
      immunosuppression, nor EBV or HHV-8 infection alone result in development of HD
      or KS. There is no clear time relationship between the development of KS and HD
      when the two occurred together in the same patient. That finding, coupled with
      the rarity of the association, suggest, that the association is more likely
      coincidental.

PMID- 10903194
TI  - An All-Dielectric Coaxial Waveguide.
AB  - An all-dielectric coaxial waveguide that can overcome problems of polarization
      rotation and pulse broadening in the transmission of optical light is presented
      here. It consists of a coaxial waveguiding region with a low index of refraction,
      bounded by two cylindrical, dielectric, multilayer, omnidirectional reflecting
      mirrors. The waveguide can be designed to support a single mode whose properties
      are very similar to the unique transverse electromagnetic mode of a traditional
      metallic coaxial cable. The new mode has radial symmetry and a point of zero
      dispersion. Moreover, because the light is not confined by total internal
      reflection, the waveguide can guide light around very sharp corners.

PMID- 10903193
TI  - Research for corresponding dental therapy for patients undergoing bone marrow and
      peripheral blood stem-cell transplantation.
AB  - In an interdisciplinary co-operation between the Haematology Department of the
      III. Medical Clinic, University of Mainz, and the Polyclinic for Restorative
      Dentistry Mainz, Germany, a total of 61 patients (33 men, 28 women, average age
      43.2 +/- 11.5 years) received dental examination just before undergoing bone
      marrow transplantation (BMT) (n = 17) and peripheral blood stem-cell
      transplantation (PBSCT) (n = 44) respectively. The aim of this study was to
      determine the frequency of dentogenic complications during the aplasia phase. -
      Patients, who were scheduled for either bone marrow or blood stem-cell
      transplantation, have been examined in view of their serious susceptibility to
      infections during the aplasia phase, even though the probability of an
      exacerbation is said to be quite low, as it has been shown in the present study.

PMID- 10903195
TI  - Holes in a Quantum Spin Liquid.
AB  - Magnetic neutron scattering provides evidence for nucleation of antiferromagnetic
      droplets around impurities in a doped nickel oxide-based quantum magnet. The
      undoped parent compound contains a spin liquid with a cooperative singlet ground
      state and a gap in the magnetic excitation spectrum. Calcium doping creates
      excitations below the gap with an incommensurate structure factor. We show that
      weakly interacting antiferromagnetic droplets with a central phase shift of pi
      and a size controlled by the correlation length of the quantum liquid can account
      for the data. The experiment provides a quantitative impression of the magnetic
      polarization cloud associated with holes in a doped transition metal oxide.

PMID- 10903196
TI  - Subatomic Features on the Silicon (111)-(7x7) Surface Observed by Atomic Force
      Microscopy.
AB  - The atomic force microscope images surfaces by sensing the forces between a sharp
      tip and a sample. If the tip-sample interaction is dominated by short-range
      forces due to the formation of covalent bonds, the image of an individual atom
      should reflect the angular symmetry of the interaction. Here, we report on a
      distinct substructure in the images of individual adatoms on silicon (111)-(7x7),
      two crescents with a spherical envelope. The crescents are interpreted as images
      of two atomic orbitals of the front atom of the tip. Key for the observation of
      these subatomic features is a force-detection scheme with superior noise
      performance and enhanced sensitivity to short-range forces.

PMID- 10903197
TI  - Mass Balance of the Greenland Ice Sheet at High Elevations.
AB  - Comparison of ice discharge from higher elevation areas of the entire Greenland
      Ice Sheet with total snow accumulation gives estimates of ice thickening rates
      over the past few decades. On average, the region has been in balance, but with
      thickening of 21 centimeters per year in the southwest and thinning of 30
      centimeters per year in the southeast. The north of the ice sheet shows less
      variability, with average thickening of 2 centimeters per year in the northeast
      and thinning of about 5 centimeters per year in the northwest. These results
      agree well with those from repeated altimeter surveys, except in the extreme
      south, where we find substantially higher rates of both thickening and thinning.

PMID- 10903198
TI  - Greenland Ice Sheet: High-Elevation Balance and Peripheral Thinning.
AB  - Aircraft laser-altimeter surveys over northern Greenland in 1994 and 1999 have
      been coupled with previously reported data from southern Greenland to analyze the
      recent mass-balance of the Greenland Ice Sheet. Above 2000 meters elevation, the
      ice sheet is in balance on average but has some regions of local thickening or
      thinning. Thinning predominates at lower elevations, with rates exceeding 1 meter
      per year close to the coast. Interpolation of our results between flight lines
      indicates a net loss of about 51 cubic kilometers of ice per year from the entire
      ice sheet, sufficient to raise sea level by 0.13 millimeter per year
      approximately 7% of the observed rise.

PMID- 10903199
TI  - Stability of Ferropericlase in the Lower Mantle.
AB  - We have heated ferropericlases (Mg(0.60)Fe(0.40))O and (Mg(0.50)Fe(0.50))O to
      temperatures of 1000 kelvin at pressures of 86 gigapascals, simulating the
      stability of the solid solution at physical conditions relevant to Earth's lower
      mantle. The in situ x-ray study of the externally heated samples in a Mao-Bell
      type diamond anvil cell shows that ferropericlase may dissociate into magnesium
      rich and iron-rich oxide components. The result is important because the
      decomposition of ferropericlase into lighter and heavier phases will cause
      dynamic effects that could lead to mantle heterogeneity.

PMID- 10903200
TI  - Pattern of marine mass extinction near the Permian-Triassic boundary in South
      China.
AB  - The Meishan section across the Permian-Triassic boundary in South China is the
      most thoroughly investigated in the world. A statistical analysis of the
      occurrences of 162 genera and 333 species confirms a sudden extinction event at
      251.4 million years ago, coincident with a dramatic depletion of
      delta13C(carbonate) and an increase in microspherules.

PMID- 10903201
TI  - Negative regulation of the SHATTERPROOF genes by FRUITFULL during Arabidopsis
      fruit development.
AB  - The terminal step of fruit development in Arabidopsis involves valve separation
      from the replum, allowing seed dispersal. This process requires the activities of
      the SHATTERPROOF MADS-box genes, which promote dehiscence zone differentiation at
      the valve/replum boundary. Here we show that the FRUITFULL MADS-box gene, which
      is necessary for fruit valve differentiation, is a negative regulator of
      SHATTERPROOF expression and that constitutive expression of FRUITFULL is
      sufficient to prevent formation of the dehiscence zone. Our studies suggest that
      ectopic expression of FRUITFULL may directly allow the control of pod shatter in
      oilseed crops such as canola.

PMID- 10903202
TI  - Interdigital regulation of digit identity and homeotic transformation by
      modulated BMP signaling.
AB  - The developmental mechanisms specifying digital identity have attracted 30 years
      of intense interest, but still remain poorly understood. Here, through
      experiments on chick foot development, we show digital identity is not a fixed
      property of digital primordia. Rather, digital identity is specified by the
      interdigital mesoderm, demonstrating a patterning function for this tissue before
      its regression. More posterior interdigits specify more posterior digital
      identities, and each primordium will develop in accordance with the most
      posterior cues received. Furthermore, inhibition of interdigital bone
      morphogenetic protein (BMP) signaling can transform digit identity, suggesting a
      role for BMPs in this process.

PMID- 10903203
TI  - Evidence for ecological causation of sexual dimorphism in a hummingbird.
AB  - Unambiguous examples of ecological causes of animal sexual dimorphism are rare.
      Here we present evidence for ecological causation of sexual dimorphism in the
      bill morphology of a hummingbird, the purple-throated carib. This hummingbird is
      the sole pollinator of two Heliconia species whose flowers correspond to the
      bills of either males or females. Each sex feeds most quickly at the flower
      species approximating its bill dimensions, which supports the hypothesis that
      floral specialization has driven the evolution of bill dimorphism. Further
      evidence for ecological causation of sexual dimorphism was provided by a
      geographic replacement of one Heliconia species by the other and the subsequent
      development of a floral dimorphism, with one floral morph matching the bills of
      males and the other of females.

PMID- 10903204
TI  - Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII
      vesicles for fusion.
AB  - The guanosine triphosphatase Rab1 regulates the transport of newly synthesized
      proteins from the endoplasmic reticulum to the Golgi apparatus through
      interaction with effector molecules, but the molecular mechanisms by which this
      occurs are unknown. Here, the tethering factor p115 was shown to be a Rab1
      effector that binds directly to activated Rab1. Rab1 recruited p115 to coat
      protein complex II (COPII) vesicles during budding from the endoplasmic
      reticulum, where it interacted with a select set of COPII vesicle-associated
      SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors)
      to form a cis-SNARE complex that promotes targeting to the Golgi apparatus. We
      propose that Rab1-regulated assembly of functional effector-SNARE complexes
      defines a conserved molecular mechanism to coordinate recognition between
      subcellular compartments.

PMID- 10903205
TI  - One sequence, two ribozymes: implications for the emergence of new ribozyme
      folds.
AB  - We describe a single RNA sequence that can assume either of two ribozyme folds
      and catalyze the two respective reactions. The two ribozyme folds share no
      evolutionary history and are completely different, with no base pairs (and
      probably no hydrogen bonds) in common. Minor variants of this sequence are highly
      active for one or the other reaction, and can be accessed from prototype
      ribozymes through a series of neutral mutations. Thus, in the course of
      evolution, new RNA folds could arise from preexisting folds, without the need to
      carry inactive intermediate sequences. This raises the possibility that
      biological RNAs having no structural or functional similarity might share a
      common ancestry. Furthermore, functional and structural divergence might, in some
      cases, precede rather than follow gene duplication.

PMID- 10903207
TI  - A neural basis for general intelligence.
AB  - Universal positive correlations between different cognitive tests motivate the
      concept of "general intelligence" or Spearman's g. Here the neural basis for g is
      investigated by means of positron emission tomography. Spatial, verbal, and
      perceptuo-motor tasks with high-g involvement are compared with matched low-g
      control tasks. In contrast to the common view that g reflects a broad sample of
      major cognitive functions, high-g tasks do not show diffuse recruitment of
      multiple brain regions. Instead they are associated with selective recruitment of
      lateral frontal cortex in one or both hemispheres. Despite very different task
      content in the three high-g-low-g contrasts, lateral frontal recruitment is
      markedly similar in each case. Many previous experiments have shown these same
      frontal regions to be recruited by a broad range of different cognitive demands.
      The results suggest that "general intelligence" derives from a specific frontal
      system important in the control of diverse forms of behavior.

PMID- 10903206
TI  - Group II introns designed to insert into therapeutically relevant DNA target
      sites in human cells.
AB  - Mobile group II intron RNAs insert directly into DNA target sites and are then
      reverse-transcribed into genomic DNA by the associated intron-encoded protein.
      Target site recognition involves modifiable base-pairing interactions between the
      intron RNA and a >14-nucleotide region of the DNA target site, as well as fixed
      interactions between the protein and flanking regions. Here, we developed a
      highly efficient Escherichia coli genetic assay to determine detailed target site
      recognition rules for the Lactococcus lactis group II intron Ll.LtrB and to
      select introns that insert into desired target sites. Using human
      immunodeficiency virus-type 1 (HIV-1) proviral DNA and the human CCR5 gene as
      examples, we show that group II introns can be retargeted to insert efficiently
      into virtually any target DNA and that the retargeted introns retain activity in
      human cells. This work provides the practical basis for potential applications of
      targeted group II introns in genetic engineering, functional genomics, and gene
      therapy.

PMID- 10903208
TI  - The role of GTP-binding protein activity in fast central synaptic transmission.
AB  - Guanosine 5'-triphosphate (GTP)-binding proteins (G proteins) are involved in
      exocytosis, endocytosis, and recycling of vesicles in yeast and mammalian
      secretory cells. However, little is known about their contribution to fast
      synaptic transmission. We loaded guanine nucleotide analogs directly into a giant
      nerve terminal in rat brainstem slices. Inhibition of G-protein activity had no
      effect on basal synaptic transmission, but augmented synaptic depression and
      significantly slowed recovery from depression. A nonhydrolyzable GTP analog
      blocked recovery of transmission from activity-dependent depression. Neither
      effect was accompanied by a change in presynaptic calcium currents. Thus, G
      proteins contribute to fast synaptic transmission by refilling synaptic vesicles
      depleted after massive exocytosis.

PMID- 10903209
TI  - Abolition and reversal of strain differences in behavioral responses to drugs of
      abuse after a brief experience.
AB  - Inbred strains of mice are largely used to identify the genetic basis of normal
      and pathological behaviors. This report demonstrates that a moderate period of
      food shortage, an ecologically common experience, can reverse or abolish strain
      differences in behavioral responses to the abused psychostimulant amphetamine.
      The period of food shortage occurred when the animals were mature and was
      terminated before the administration of amphetamine. Strain differences in
      behavior appear highly dependent on environmental experiences. Consequently, to
      identify biological determinants of behavior, an integrated approach considering
      the interaction between environmental and genetic factors needs to be used.

PMID- 10903210
TI  - Is there a role for glucocorticoid receptor beta in glucocorticoid-dependent
      asthmatics?

PMID- 10903211
TI  - Smoking and lung cancer.

PMID- 10903212
TI  - Glucocorticoid receptor alpha and beta in glucocorticoid dependent asthma.
AB  - Patients with glucocorticoid (GC)-dependent asthma present an ongoing
      inflammation of the airways despite chronic long-term treatment with oral GC.
      Interleukin (IL)-8 and granulocyte/macrophage colony-stimulating factor (GM-CSF)
      have been implicated in airway inflammation in severe asthma and their synthesis
      is normally repressed by GC. To further characterize the inflammatory process in
      GC-dependent asthma, we measured the release of IL-8 and GM-CSF by peripheral
      blood mononuclear cells (PBMC) of eight normal subjects, six untreated controlled
      asthmatics, six untreated uncontrolled asthmatics, and nine GC-dependent
      asthmatics. We show that PBMC from GC-dependent asthmatics released high amounts
      of these cytokines despite chronic in vivo exposure to GC (p < 0.001 versus
      normal subjects). In contrast, when untreated uncontrolled asthmatics were given
      a short course of oral GC, IL-8 and GM-CSF production was inhibited (p = 0.0078).
      Release of IL-8 and GM-CSF by PBMC of GC-dependent asthmatics was reduced after
      in vitro GC treatment (p < 0.002). We investigated whether the incapacity of GC
      to inhibit production of these cytokines in vivo was the result of a
      dysregulation of the glucocorticoid receptor (GR) in GC-dependent asthma. GRalpha
      and GRbeta are, respectively, the functional receptor and a putative dominant
      negative form of the receptor. Western blot and polymerase chain reaction (PCR)
      analyses indicated that GRalpha was expressed at similar level in all groups and
      was largely predominant over GRbeta. Thus, persistent release of IL-8 and GM-CSF
      in GC-dependent asthma is not associated with low expression of GRalpha or
      overexpression of GRbeta.

PMID- 10903213
TI  - The use of cylexin (CY-1503) in prevention of reperfusion lung injury in patients
      undergoing pulmonary thromboendarterectomy.
AB  - Pulmonary thromboendartectomy (PTE) for chronic thromboembolic pulmonary
      hypertension may be complicated by reperfusion lung injury. This has previously
      been demonstrated to be neutrophil-mediated. We postulated that blocking selectin
      mediated adhesion of neutrophils to the endothelium with Cylexin (CY-1503) would
      prevent reperfusion lung injury in this patient population. In this double-blind,
      randomized, placebo-controlled, parallel study, 26 patients received Cylexin the
      day of surgery and 25 received placebo. Significantly fewer patients in the
      treated group (31%) compared with the placebo group (60%) developed lung injury
      (p = 0.036). However, the average number of days of mechanical ventilation, days
      in the intensive care unit (ICU) and hospital, as well as mortality were not
      significantly different between the treatment groups. Those with reperfusion lung
      injury had significantly elevated percent neutrophils, total protein, and soluble
      P-selectin in bronchoalveolar lavage fluid compared with those without lung
      injury. We conclude that reperfusion lung injury after PTE is a high-permeability
      lung injury and its incidence can be reduced by the administration of Cylexin on
      the day of surgery.

PMID- 10903214
TI  - Selective NOS inhibition restores myocardial contractility in endotoxemic rats;
      however, myocardial NO content does not correlate with myocardial dysfunction.
AB  - The role of nitric oxide (NO) in lipopolysaccharide (LPS)-induced myocardial
      dysfunction remains controversial as some investigators concluded that inhibition
      of NO synthesis improves left ventricular (LV) contractility, whereas others did
      not. We investigated the relationship between LPS-induced LV dysfunction and LV
      NO production. We postulated that high myocardial NO concentrations would
      correspond to decreased contractility and low NO concentrations would correspond
      to recovery. In a rat model of endotoxemia, we used the isolated papillary
      preparation to assess inotropic dysfunction. We measured LV NO content and
      hemodynamics at baseline, 4, 16, and 48 h after LPS administration. LPS caused a
      decrease in LV contractility at 16 h with recovery at 48 h. Myocardial NO levels
      were elevated at all time periods. However, at 48 h in spite of normalization of
      LV contractility, myocardial NO content remained elevated. Pretreatment of LPS
      animals with the nonselective nitric oxide synthase (NOS) inhibitor N (G)-nitro-L
      arginine methyl ester (L-NAME) worsened LV contractility, decreased LV NO
      content, and increased mortality. However, pretreatment with the relatively
      selective inducible NOS (iNOS) inhibitor S-methylisothiourea sulfate (SMT)
      restored LV contractility. Myocardial NO content in the SMT was lower than that
      of the LPS only group, but higher than the L-NAME group. We conclude that SMT is
      beneficial to myocardial contractility in this model of endotoxemia, whereas
      pretreatment with L-NAME is associated with further deterioration of
      contractility and increased mortality. Moreover, our data indicate that high
      myocardial NO concentrations do not necessarily correlate with decreased
      contractility.

PMID- 10903215
TI  - Adverse ventilatory strategy causes pulmonary-to-systemic translocation of
      endotoxin.
AB  - Accumulating evidence strongly suggests that ventilatory strategy has an
      important impact on development of lung injury and patient outcome. Adverse
      ventilatory strategies have been shown to cause release of pulmonary-derived
      cytokines and may permit bacterial translocation from the lung to the systemic
      circulation. Because endotoxin is a potent and clinically important stimulant of
      cytokine-mediated systemic inflammatory responses that can lead to multiorgan
      failure, we investigated the effects of ventilatory strategy on lung-to-systemic
      translocation of endotoxin. We studied the effects of protective (tidal volume
      [VT] 5 ml. kg(-)(1), positive end-expiratory pressure [PEEP] 10 to 12.5 cm H(2)O)
      versus nonprotective (VT 12 ml. kg(-)(1), PEEP zero) ventilatory strategy on
      translocation of endotracheally instilled endotoxin. Anesthetized New Zealand
      White rabbits were subjected to saline lung lavage, and 32 were randomized to one
      of four groups: PS (protective ventilation + instilled saline); PE (protective
      ventilation + instilled endotoxin); NS (nonprotective ventilation + instilled
      saline); NE (nonprotective ventilation + instilled endotoxin), and ventilated for
      3 h. Plasma endotoxin levels increased significantly in the NE group, and
      remained low and unchanged in the other groups. Peak levels of plasma tumor
      necrosis factor-alpha (TNF-alpha) were higher in NE versus other groups. Pa(O(2))
      and mean arterial pressure (Pa) were lowest, and requirement for pressor and
      bicarbonate support greatest, in the NE group. Finally, plasma endotoxin levels
      were significantly greater in eventual nonsurvivors than survivors. These data
      provide convincing evidence for pulmonary translocation of lung-derived
      endotoxin. This translocation depends on ventilatory strategy, and suggests a
      pathophysiologic link between ventilatory strategy and outcome.

PMID- 10903216
TI  - The prevalence of gastroesophageal reflux in asthma patients without reflux
      symptoms.
AB  - Gastroesophageal reflux is a potential trigger of asthma that may be clinically
      silent. This study examines the prevalence of gastroesophageal reflux in asthma
      patients without reflux symptoms. This prospective cohort study evaluated 26
      patients with stable asthma without reflux symptoms using esophageal manometry
      and 24-h esophageal pH testing. Gastroesophageal reflux was considered present if
      esophageal acid contact times were abnormal. Demographic variables were analyzed
      to determine if they predicted the presence of gastroesophageal reflux. Asthma
      patients with asymptomatic gastroesophageal reflux were compared with 30 age
      matched asthma patients with symptomatic gastroesophageal reflux. The prevalence
      of abnormal 24-h esophageal pH tests in asthma patients without reflux symptoms
      was 62% (16 of 26). Demographic variables did not predict abnormal 24-h
      esophageal pH tests in asthma patients with asymptomatic gastroesophageal reflux.
      Asthma patients with asymptomatic gastroesophageal reflux had higher amounts of
      proximal esophageal acid exposure (p < 0.05) compared with asthma patients with
      symptomatic gastroesophageal reflux. Because demographic variables do not predict
      abnormal 24-h esophageal pH tests in asthma patients without reflux symptoms, 24
      h esophageal pH testing is required. This study suggests that gastroesophageal
      reflux is present in asthma patients, even in the absence of esophageal symptoms.

PMID- 10903217
TI  - Effect of losartan, a type 1 angiotensin II receptor antagonist, on bronchial
      hyperresponsiveness to methacholine in patients with bronchial asthma.
AB  - It is unclear whether angiotensin II receptors are involved in bronchial
      hyperresponsiveness in asthmatic patients. We examined the effect of losartan, a
      specific angiotensin II type 1 (AT1) receptor antagonist, on bronchial
      responsiveness to inhaled methacholine in eight patients with stable asthma.
      Bronchial responsiveness to methacholine, assessed as the concentration of
      methacholine producing a 20% fall in FEV(1) (PC(20)-FEV(1)) and a 35% fall in
      standardized partial expiratory flow at 40% of FVC (PC(35)-PEF(40)), was measured
      on two occasions 2 wk apart. Losartan (50 mg once a day) or a placebo was orally
      administered for 1 wk before methacholine provocation test in a double-blind,
      randomized, crossover fashion. Although the PC(20)-FEV(1) values after placebo
      (2.037 [geometric standard error of the mean, GSEM = 0.210] mg/ml) and losartan
      (2.098 [GSEM, 0.239] mg/ml) were identical (p = 0.840), the geometric mean PC(35)
      PEF(40) values significantly (p = 0.034) increased from 0.258 (GSEM, 0.156) mg/ml
      with placebo to 0.456 (GSEM, 0.186) mg/ml with losartan. We conclude that AT1
      receptors are involved in bronchial hyperresponsiveness in asthmatic patients.
      This is the first report demonstrating the involvement of AT1 receptors in
      bronchial asthma.

PMID- 10903218
TI  - Type 1 angiotensin II receptor antagonism reduces antigen-induced airway
      reactions.
AB  - Although the renin-angiotensin system is activated in patients with asthma during
      severe acute attacks and angiotensin II has been shown to cause
      bronchoconstriction in patients with asthma, the role of angiotensin II in
      patients with asthma is unclear. We investigated the effects of two specific
      antagonists at type 1 and type 2 angiotensin II receptors, candesartan cilexetil
      (TCV-116) and PD123319, on antigen-induced airway reactions in guinea pigs. Sixty
      minutes after intraperitoneal administration of candesartan cilexetil (0.1, 1.0,
      or 10 mg/kg) or PD123319 (30 mg/kg), animals received an antigen challenge.
      Airway responsiveness to inhaled methacholine was assessed as the dose of
      methacholine required to produce a 200% increase in the pressure at the airway
      opening (PC(200)). Differential cell counts in bronchoalveolar lavage fluids
      (BALF) were measured 24 h after antigen challenge. Candesartan cilexetil did not
      inhibit antigen-induced bronchoconstriction in sensitized guinea pigs or alter
      PC(200) in nonsensitized guinea pigs. Antigen inhalation significantly increased
      bronchoconstrictor responses to methacholine and increased airway accumulation of
      eosinophils; both responses showed dose-dependent prevention by candesartan but
      not by PD123319. These results indicate that endogenous angiotensin II promotes
      antigen-induced airway hyperresponsiveness and eosinophil accumulation by acting
      at type 1 receptors.

PMID- 10903219
TI  - Relationship between increased airway responsiveness and asthma severity in the
      childhood asthma management program.
AB  - The relationship between increased airway responsiveness and asthma severity in
      children is unclear. The Childhood Asthma Management Program (CAMP) with 1,041
      children with mild to moderate asthma offers an opportunity to relate the
      concentration of methacholine that causes a 20% fall in FEV(1) (PC(20)) to level
      of lung function, occurrence of respiratory symptoms, duration of disease, and
      assessment of severity by clinical staff. Decreasing PC(20) was found to be
      associated with lower levels of lung function (prebronchodilator percent
      predicted FEV(1): r = 0.29, beta = 3.5, p < 0.001), the occurrence of chronic
      asthma symptoms, persistent wheezing (odds ratio [OR] = 1.66, p < 0.001),
      subjective clinical staff assessment of asthma severity (p < 0.001), and longer
      duration of asthma (r = -0.11, beta = -0.20, p < 0.002). These data provide
      evidence that the degree of airway responsiveness is linked to disease severity
      in children with mild to moderate asthma.

PMID- 10903220
TI  - Transcriptional potencies of inhaled glucocorticoids.
AB  - Glucocorticoids (GC) are the most effective anti-inflammatory drugs used in
      asthma. By a process called trans-activation, they increase the transcription of
      genes involved in either beneficial processes or certain side effects. Through
      trans-repression, they inhibit the transcription factors nuclear factor kappa B
      (NF-kappaB) and activator protein-1 (AP-1), thereby decreasing the expression of
      many genes encoding inflammatory mediators such as the cytokine RANTES. We have
      measured the trans-activation and trans-repression potencies of the five
      currently available inhaled GC using reporter gene assays. The rank order of
      trans-activation potencies in HeLa cells stably transfected with a GC-inducible
      luciferase gene was fluticasone propionate > budesonide and triamcinolone
      acetonide > beclomethasone dipropionate and flunisolide. For all GC except
      beclomethasone dipropionate, there was a highly significant correlation between
      their potency to trans-activate in HeLa cells and their capacity to induce the
      gluconeogenic enzyme tyrosine aminotransferase in hepatoma tissue culture (HTC)
      cells. The rank order of trans-repression potencies in A549 lung cells
      transiently transfected with an AP-1- or NF-kappaB-dependent luciferase gene was
      fluticasone propionate > budesonide > beclomethasone dipropionate, triamcinolone
      acetonide, and flunisolide. The same rank order was found for inhibition of
      RANTES release. Thus, determination of trans-repression and trans-activation
      potencies of GC may help to predict their capacity to produce anti-inflammatory
      and side effects, respectively.

PMID- 10903221
TI  - Effect of antiretroviral therapy on the incidence of bacterial pneumonia in
      patients with advanced HIV infection.
AB  - To determine the relationship of combination antiretroviral therapy and bacterial
      pneumonia, we assessed incidence of and risk factors for bacterial pneumonia in
      1,898 human immunodeficiency virus (HIV)-infected patients with CD4 cell counts <
      200/mm(3) followed in the Johns Hopkins HIV clinic between 1993 and 1998. A total
      of 352 episodes of bacterial pneumonia occurred during 2,310 patient-years of
      follow-up. Incidence of bacterial pneumonia decreased from 22.7 episodes/100
      person-years (py) in the first half of 1993 to 12.3 episodes/100 py in the first
      half of 1996, reaching a nadir of 9.1 episodes/100 py in the second half of 1997
      (p < 0.05). The use of protease inhibitor-containing regimens was associated with
      a decreased risk of bacterial pneumonia (risk ratio [RR] 0.55, 95% CI 0.31 to
      0.94). Lower CD4 cell counts (RR 2.22, 95% CI 1.54 to 3.18), injection drug use
      as HIV transmission category (RR2.0, 95% CI 1.43 to 2.76), and prior Pneumocystis
      carinii pneumonia (RR 3.88, 95% CI 1.65 to 9.16) were also significantly
      associated with bacterial pneumonia. Trimethoprim-sulfamethoxazole and macrolide
      use were not significantly associated with risk of bacterial pneumonia. There has
      been a dramatic decline in the incidence of bacterial pneumonia resulting from
      the use of combination antiretroviral therapy containing protease inhibitors.

PMID- 10903222
TI  - Differences in incidence of reported asthma related to age in men and women. A
      retrospective analysis of the data of the European Respiratory Health Survey.
AB  - Sex differences in asthma prevalence and morbidity, assessed with different
      methods in different populations, have raised several hypotheses about the
      different susceptibility to asthma in men and women. However, information on the
      incidence of asthma by age and sex is limited. The aim of this study was to
      estimate the age- and sex-specific incidence of asthma from birth to 44 yr of age
      in men and women across several countries, and to evaluate the main factors
      influencing asthma incidence in young adults. The data of the European Community
      Respiratory Health Survey, an international, cross-sectional, population-based
      survey, which were collected in 16 countries from 1991 to 1993 according to a
      common protocol, and which pertained to 18,659 subjects, were analyzed
      retrospectively, using the reported age of the first attack as the onset of
      asthma. During childhood, girls had a significantly lower risk of developing
      asthma than did boys (relative risk [RR]: 0.74 and 0.56 in the 0- to 5-yr and 5-
      to 10-yr age classes, respectively). Around puberty, the risk was almost equal in
      the two sexes (RR = 0.84; 95% confidence interval [CI]: 0.65 to 1.10 in the 10 to
      15-yr age class). After puberty, the risk in women was always significantly
      higher than that in men (RR: 1.38 to 5.91). This pattern was consistent in all of
      the 16 countries studied, and was not influenced by recall or cohort effects.
      When the effects of airway caliber and smoking were studied with a case-control
      design, the results showed that women's greater susceptibility to asthma in early
      adulthood was at least partly, explained by their smaller airway caliber (the OR
      decreased from 2. 04 [95% CI: 1.32 to 3.15] to 1.47 [95% CI: 0.89 to 2.44] after
      controlling for height-adjusted FEV(1)); while smoking did not increase the risk.
      This analysis strongly confirms that the incidence of asthma shows a sex reversal
      during puberty, and suggests that airway caliber, in addition to hormonal
      factors, could play an important role in explaining the different patterns of
      asthma incidence in men and women.

PMID- 10903223
TI  - The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to
      regular use of albuterol in asthma.
AB  - Inhaled beta-adrenergic agonists are the most commonly used medications for the
      treatment of asthma although there is evidence that regular use may produce
      adverse effects in some patients. Polymorphisms of the beta(2)-adrenergic
      receptor (beta(2)-AR) can affect regulation of the receptor. Smaller studies
      examining the effects of such polymorphisms on the response to beta-agonist
      therapy have produced inconsistent results. We examined whether polymorphisms at
      codon 16 (beta(2)-AR-16) and codon 27 (beta(2)-AR-27) of the beta(2)-AR might
      affect the response to regular versus as-needed use of albuterol by genotyping
      the 190 asthmatics who had participated in a trial examining the effects of
      regular versus as needed albuterol use. During the 16-wk treatment period there
      was a small decline in morning peak expiratory flow in patients homozygous for
      arginine at B(2)-AR-16 (Arg/Arg) who used albuterol regularly. This effect was
      magnified during a 4-wk run out period, during which all patients returned to
      using as-needed albuterol, so that by the end of the study Arg Arg patients who
      had regularly used albuterol had a morning peak expiratory flow 30. 5 +/- 12.1
      L/min lower (p = 0.012) than Arg/Arg patients who had used albuterol on an as
      needed basis. There was no decline in peak flow with regular use of albuterol in
      patients who were homozygous for glycine at beta(2)-AR-16. Evening peak
      expiratory flow also declined in the Arg/Arg patients who used albuterol
      regularly but not in those who used albuterol on an as-needed basis. No
      significant differences in outcomes between regular and as-needed treatment were
      associated with polymorphisms at position 27 of the beta(2)-AR. No other
      differences in asthma outcomes that we investigated occurred in relation to these
      beta(2)-AR polymorphisms. Polymorphisms of the beta(2)-AR may influence airway
      responses to regular inhaled beta-agonist treatment.

PMID- 10903224
TI  - Respiratory disturbance index: an independent predictor of mortality in coronary
      artery disease.
AB  - Cardiovascular mortality was prospectively investigated in consecutive coronary
      artery disease (CAD) patients with versus without obstructive sleep apnea (OSA)
      during a follow-up period of 5 yr. An overnight sleep/ventilatory study was
      performed in patients requiring intensive care (n = 62, mean age 67.6 +/- 10.4
      yr, range 44 to 86) during a stable condition (New York Heart Association [NYHA]
      functional class I-II) 4 to 21 mo after discharge from the hospital. OSA, defined
      as a respiratory disturbance index (RDI) of 10/h or more was found in 19 patients
      (mean RDI 17.5 +/- 8.3). Three OSA subjects who were successfully treated with
      continuous positive airway pressure (CPAP) during the observation period were
      excluded from the final analysis. There was no statistically significant
      difference (Fisher two-tailed exact test) between the OSA and non-OSA patient
      groups in terms of number of elderly subjects (age >/= 65 yr), gender, obesity
      (body mass index [BMI] >/= 30 kg/m(2)), smoking history, presence of
      hypertension, diabetes mellitus, hypercholesterolemia, or history of myocardial
      infarction at the study start. During the follow-up period, cardiovascular death
      occurred in six of 16 OSA patients (37.5%) compared with 4 (9.3%) in the non-OSA
      group (p = 0.018). The univariate predictors of cardiovascular mortality were RDI
      (p = 0.007), OSA (p = 0.014), age at baseline (p = 0.028), hypertension at
      baseline (p = 0.036), history of never-smoking (p = 0.031), and digoxin treatment
      during the follow-up period (p = 0.013). In a Cox multiple conditional regression
      model, RDI remained as an independent predictor of cardiovascular mortality (exp
      beta = 1.13, 95% confidence interval [CI] 1.05 to 1.21, two-sided p < 0.001). We
      conclude that untreated OSA is associated with an increased risk of
      cardiovascular mortality in patients with CAD. Furthermore, it appears
      appropriate that RDI is taken into consideration when evaluating secondary
      prevention models in CAD.

PMID- 10903225
TI  - Comparison of esophageal pressure with pulse transit time as a measure of
      respiratory effort for scoring obstructive nonapneic respiratory events.
AB  - Obstructive nonapneic respiratory events (ONAREs) are much more difficult to
      detect and classify than apneas unless sensitive measures of respiratory effort
      and airflow are employed. The aim of this study was to compare two measures of
      respiratory effort, esophageal pressure monitoring (Pes) and pulse transit time
      (PTT), for scoring of ONAREs by visual analysis. Nine men (age 49 +/- 10 yr) with
      mild to moderate sleep apnea syndrome (AHI of 25.1 +/- 10. 8/h) were studied and
      340 ONAREs (hypopneas and upper airway resistance episodes) were randomly
      selected for scoring by two experienced observers. Each observer blindly scored
      each ONARE twice (once with Pes and once with PTT) with a concurrent
      pneumotachography trace available for airflow quantification. This permitted the
      respiratory events scored with PTT to be compared with those scored with Pes, and
      in addition interobserver variability could be assessed for each signal. Even
      though standard criteria were used for scoring, there was significant
      interobserver variability for both Pes (29.7%) and PTT (37.1%). Taking those
      events for which there was agreement between the observers, PTT had a sensitivity
      of 79.9% and a positive predictive value of 91.2% (using Pes as the gold
      standard). In those ONAREs for which there was agreement between the two
      observers there was a larger percentage reduction in airflow compared to ONAREs
      that did not concur (51 versus 30.3%, p < 0.001), a larger increase in
      respiratory effort as assessed by PTT (slope of PTT: 23.1 versus 14. 3 arbitrary
      units, p < 0.01), and a higher incidence in autonomic microarousals detected with
      PTT (90 versus 45% of ONAREs, p < 0.006). Subtle respiratory events are more
      difficult to detect than apneas or frank hypopneas. When comparing PTT with
      esophageal pressure in detecting those events the sensitivity of PTT is good but
      limited when the reduction in airflow, the increase in respiratory effort, or the
      arousal reaction is the less clear. However, PTT appears to be a good noninvasive
      alternative to Pes in the detection of nonapneic obstructive respiratory events,
      and its ability to detect autonomic arousal gives this physiological signal added
      clinical usefulness.

PMID- 10903226
TI  - Accuracy of an unattended home CPAP titration in the treatment of obstructive
      sleep apnea.
AB  - Treatment of sleep apnea-hypopnea syndrome (SAHS) by fixed continuous positive
      airway pressure (CPAP) requires an in-laboratory titration procedure to determine
      the effective pressure level (Peff ). We recently reported that one auto-CPAP
      machine can be used without titration study allowing Peff determination. The aim
      of this study was to evaluate the accuracy of an auto CPAP trial at home. A 1- or
      2-wk automatic CPAP trial was done at home in 40 patients by estimating the
      reference pressure (Pref ) to be set and a Pref + 3 cm H(2)O/-4 cm H(2)O pressure
      interval. Peff was then determined according to the percentage of CPAP time that
      was spent </= Pref. This Peff value was set on a fixed CPAP machine for two
      additional weeks and a control sleep study was done. The pressure setting on
      fixed CPAP had to be increased by 1 +/- 1 cm H(2)O (mean +/- SD) above estimated
      Pref. Sleep improved with fixed CPAP, with a normalization of the apnea +
      hypopnea index (AHI) in 38 of 40 and resumption of diurnal hypersomnolence. CPAP
      compliance remained excellent (CPAP use: 6.1 +/- 1.7 h/ night) after 6.5 +/- 2.8
      mo of CPAP treatment. These results indicate that auto-CPAP therapy represents a
      new useful and accurate way to identify conventional CPAP setting outside
      hospital and sleep laboratories.

PMID- 10903227
TI  - A single intrapleural injection of transforming growth factor-beta(2) produces an
      excellent pleurodesis in rabbits.
AB  - The purpose of the present study was to determine whether the intrapleural
      injection of transforming growth factor beta(2) (TGF-beta(2)) would produce a
      pleurodesis in rabbits. Single intrapleural injections of TGF-beta(2) at doses of
      5.00 microg (n = 12), 1.67 microg (n = 10), 0.50 microg (n = 10), or 0.167 microg
      (n = 4), or of the parenteral buffer alone (n = 5) were given in a volume of 2 ml
      to New Zealand white rabbits. Chest tubes were left in place for at least 72 h.
      Pleural fluid was aspirated at 24-h intervals and was measured and subjected to
      chemical analysis. The animals were killed 14 d after the injection. The
      intrapleural injection of TGF-beta(2) resulted in a dose-dependent pleurodesis
      (on a scale of 0 to 4, where 0 = no pleurodesis and 4 = complete pleurodesis)
      with mean scores of 3.6, 2.6, 1.5, 0.7, and 0.3 for the groups that received 5.0,
      1.67, 0.50, and 0.167 microg of TGF-beta(2) and buffer alone, respectively.
      Intrapleural injection of the larger doses of TGF-beta(2) resulted in the
      formation of a large amount of pleural fluid. The fluid had a significantly lower
      white blood cell (WBC) count and lactate dehydrogenase (LDH) level than did the
      fluid that results from the intrapleural injection of 10 mg/kg doxycycline or 400
      mg/kg talc slurry. On the basis of this study we conclude that a single
      intrapleural injection of TGF-beta(2) induces pleurodesis in a dose-dependent
      manner. A dose of 5.0 microg produced satisfactory pleurodesis in almost all of
      the rabbits so treated. Larger doses of TGF-beta(2) induced larger pleural
      effusions with relatively low pleural fluid WBC counts and LDH levels. The
      ability of TGF-beta to produce a pleurodesis in patients with recurrent pleural
      effusions or pneumothorax should be investigated. A single intrapleural injection
      of TGF-beta(2) may produce a pleurodesis both safely and painlessly.

PMID- 10903228
TI  - Interleukin 16 and T-cell chemoattractant activity in bronchoalveolar lavage 24
      hours after allergen challenge in asthma.
AB  - IL-16 has been shown to be one of the earliest CD4(+) cell chemoattractants
      present in BAL 4-6 h after antigen challenge but little is known about its
      persistence and biological activity after 6 h. We determined the concentration of
      IL-16 using ELISA and the T-cell chemoattractant activity using a modified Boyden
      chamber assay in unconcentrated BAL fluid from 13 patients with mild asthma and 9
      nonatopic control subjects at baseline and 24 h after segmental allergen or
      saline challenge. Furthermore, the percentage of IL-16-producing T cells was
      determined in the different samples of BAL fluid using a flow cytometric
      intracellular cytokine assay. Although no substantial levels of IL-16 protein
      were detectable in BAL fluid from control subjects and patients with asthma at
      baseline and after saline challenge, IL-16 concentrations were significantly
      elevated in patients with asthma after allergen challenge (median, 97 pg/ml;
      range, 38-362 pg/ml; p < 0.01). Furthermore, there was an increased T-cell
      chemoattractant activity after allergen challenge in patients with asthma (p <
      0.01), which could be blocked by preincubation with anti-IL-16 antibodies and
      which correlated significantly with the IL-16 protein levels (R = 0.90, p < 0.01)
      and with the level of Fas ligand expression on BAL CD4(+) cells (R = 0. 80, p <
      0.05). A high percentage (mean 70-90%) of CD4(+) and CD8(+) cells stained
      positively for IL-16 in both patients with asthma and control subjects without
      differences after allergen or saline challenge. These data demonstrate that the
      increased chemotactic activity for T cells in patients with asthma is mainly
      attributable to IL-16. Although T cells by themselves are able to produce IL-16,
      other cells, such as epithelial cells, have to be considered as further sources
      for this cytokine in patients with asthma.

PMID- 10903229
TI  - Hospitalization among workers compensated for occupational asthma.
AB  - Occupational asthma (OA) can cause persistent symptoms, but populations with OA
      have not been followed for the development of serious outcomes such as
      hospitalization. Subjects receiving compensation for OA during 1980-1993, and a
      comparison sample of workers with musculoskeletal injuries (INJ) were identified
      from the Ontario Workers' Compensation Board. We also identified for comparison a
      group of asthmatic patients (AP) seen at a tertiary care hospital clinic during
      the same period. The file was matched with the Ontario Ministry of Health data
      base of hospitalizations through 1996. We compared the frequency of
      hospitalization of the subgroups with that expected in the general population
      using standardized morbidity ratios (SMRs), and directly by proportional hazards
      regression. The study group included 844 OA claimants, 1,556 INJ claimants, and
      402 AP. Although admissions for all causes combined and respiratory disease among
      INJ were less than expected in the general population, admissions for all causes
      combined exceeded that expected among OA and AP. Admissions for respiratory
      disease were markedly greater than expected among OA (SMR 9.2) and AP (SMR 17)
      because of even greater excess admissions for asthma (SMRs 45 and 81,
      respectively). Compared with those with INJ, those with OA were more likely to be
      hospitalized for all causes combined (adjusted relative risk [RR] 1.4, 95%
      confidence interval [CI] 1.2 to 16); cardiovascular disease (RR 1.4, 95% CI 0.9
      to 2.0); respiratory disease (RR 5.4, 95% CI 3.8 to 7.7); and asthma (RR 28.1,
      95% CI 10.2 to 77.2) but not for malignancies (RR 1.0) or injuries (RR 0.9).
      Those with OA were admitted to hospital about half as frequently as AP for
      respiratory disease and asthma (although this was modified by smoking status and
      sex), but were 30% more likely to be admitted for ischemic heart disease (IHD).
      Among the OA claimants, factors that were significantly associated with
      hospitalization for asthma included older age and exposure to agents other than
      isocyanates. Those with OA became less likely to be hospitalized for asthma with
      increasing time after onset, particularly after 5 or more years. We conclude that
      subjects with OA suffer higher rates of hospitalizations for all causes combined,
      respiratory disease, and asthma than other workers, although less than among AP
      seen at a tertiary care center.

PMID- 10903230
TI  - Noninvasive versus invasive microbial investigation in ventilator-associated
      pneumonia: evaluation of outcome.
AB  - Noninvasive and invasive diagnostic techniques have been shown to achieve
      comparable performances in the evaluation of suspected ventilator-associated
      pneumonia (VAP). We studied the impact of both approaches on outcome in a
      prospective, open, and randomized study in three intensive care units (ICUs) of a
      1,000-bed tertiary care university hospital. Patients with suspected VAP were
      randomly assigned to noninvasive (Group 1) versus invasive (Group 2)
      investigation (tracheobronchial aspirates [TBAS] versus bronchoscopically
      retrieved protected specimen brush [PSB] and bronchoalveolar lavage [BAL].
      Samples were cultured quantitatively, and BAL fluid (BALF) was examined for
      intracellular organisms (ICO) additionally. Initial empiric antimicrobial
      treatment was administered following the guidelines of the American Thoracic
      Society (ATS) and adjusted according to culture results (and ICO counts in Group
      2). Outcome variables included length of ICU stay and mechanical ventilation as
      well as mortality. Overall, 76 patients (39 noninvasive, 37 invasive) were
      investigated. VAP was microbiologically confirmed in 23 of 39 (59%) and 23 of 37
      (62%) (p = 0.78). There were no differences with regard to the frequencies of
      community-acquired and potentially drug-resistant microorganisms (PDRM).
      Antimicrobial treatment was changed in seven patients (18%) of Group 1 and 10
      patients (27%) of Group 2 because of etiologic findings (including five of 17
      with ICO = 2% (p = not significant [NS]). Length of ICU stay and mechanical
      ventilation were also not significantly different in both groups. Crude 30-d
      mortality was 31 of 76 (41%), and 18 of 39 (46%) in Group 1 and 14 of 37 (38%) in
      Group 2 (p = 0.46). Adjusted mortality was 16% versus 11% (p = 0.53), and
      mortality of microbiologically confirmed pneumonia 10 of 23 (44%) in both groups
      (p = 1.0). We conclude that the outcome of VAP was not influenced by the
      techniques used for microbial investigation.

PMID- 10903231
TI  - Inhibitors of tyrosine kinase signaling cascade attenuated antigen challenge of
      guinea-pig airways in vitro.
AB  - Activation of nontransmembrane protein tyrosine kinases (PTKs),
      phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK)
      has been shown to be responsible for high-affinity Fc receptor (Fcepsilon RI)
      mediated mast cell degranulation. Effects of inhibitors of the PTK signaling
      cascade on ovalbumin (OA)-induced anaphylactic contraction of isolated guinea-pig
      bronchi and release of histamine and peptidoleukotrienes from chopped lung
      preparations were studied. Genistein (30 microM) and tyrphostin 47 (50 microM),
      two PTK inhibitors, as well as LY294002 (10 microM), a selective PI3K inhibitor,
      significantly reduced (p < 0.05) peak anaphylactic bronchial contraction and
      facilitated relaxation of the contracted bronchi. PD 098059 (30 microM), a
      selective MAPK kinase inhibitor, failed to suppress OA-induced peak bronchial
      contraction, but facilitated the relaxation of the contracted bronchi (p < 0.05).
      At the same concentrations, none of these inhibitors showed any inhibitory
      effects on histamine-, leukotriene D(4) (LTD(4))- or KCl-induced bronchial
      contraction. On the other hand, these inhibitors significantly prevented (p <
      0.05) OA-induced release of both histamine and peptidoleukotrienes from chopped
      lung preparations. In addition, combined PD 098059 and LY294002 treatment
      markedly (p < 0.05) suppressed the peak anaphylactic bronchial contraction and
      facilitated relaxation of the contracted bronchi. The combination of these two
      inhibitors further inhibited the release of peptidoleukotrienes from chopped lung
      preparations. Taken together, our data show that inhibition of tyrosine kinase
      signaling cascade can markedly attenuate anaphylactic contraction of airways,
      probably via inhibition of mast cell degranulation, and that inhibitors of this
      signaling cascade may have therapeutic potential for the treatment of asthma.

PMID- 10903232
TI  - Relation between respiratory changes in arterial pulse pressure and fluid
      responsiveness in septic patients with acute circulatory failure.
AB  - In mechanically ventilated patients with acute circulatory failure related to
      sepsis, we investigated whether the respiratory changes in arterial pressure
      could be related to the effects of volume expansion (VE) on cardiac index (CI).
      Forty patients instrumented with indwelling systemic and pulmonary artery
      catheters were studied before and after VE. Maximal and minimal values of pulse
      pressure (Pp(max) and Pp(min)) and systolic pressure (Ps(max) and Ps(min)) were
      determined over one respiratory cycle. The respiratory changes in pulse pressure
      (DeltaPp) were calculated as the difference between Pp(max) and Pp(min) divided
      by the mean of the two values and were expressed as a percentage. The respiratory
      changes in systolic pressure (DeltaPs) were calculated using a similar formula.
      The VE-induced increase in CI was >/= 15% in 16 patients (responders) and < 15%
      in 24 patients (nonresponders). Before VE, DeltaPp (24 +/- 9 versus 7 +/- 3%, p <
      0.001) and DeltaPs (15 +/- 5 versus 6 +/- 3%, p < 0.001) were higher in
      responders than in nonresponders. Receiver operating characteristic (ROC) curves
      analysis showed that DeltaPp was a more accurate indicator of fluid
      responsiveness than DeltaPs. Before VE, a DeltaPp value of 13% allowed
      discrimination between responders and nonresponders with a sensitivity of 94% and
      a specificity of 96%. VE-induced changes in CI closely correlated with DeltaPp
      before volume expansion (r(2) = 0. 85, p < 0.001). VE decreased DeltaPp from 14
      +/- 10 to 7 +/- 5% (p < 0.001) and VE-induced changes in DeltaPp correlated with
      VE-induced changes in CI (r(2) = 0.72, p < 0.001). It was concluded that in
      mechanically ventilated patients with acute circulatory failure related to
      sepsis, analysis of DeltaPp is a simple method for predicting and assessing the
      hemodynamic effects of VE, and that DeltaPp is a more reliable indicator of fluid
      responsiveness than DeltaPs.

PMID- 10903233
TI  - Ventilator-induced overdistension in children: dynamic versus low-flow inflation
      volume-pressure curves.
AB  - We applied to 20 paralyzed ventilated children (0.15 to 14.3 yr, six with acute
      respiratory distress syndrome [ARDS]) the low-flow inflation (LFI) technique
      providing quasi-static volume-pressure (V-P) curves and compared the assessment
      of overdistension (OD) on dynamic and LFI (reference) inspiratory V-P curves.
      Dynamic curves were obtained at the airway opening during regular constant flow
      ventilation (Servo 300). Then LFI curves were obtained. Two analyses were
      performed: First, the nonlinear coefficient c of a second order polynomial
      equation (SOPE) fitted to dynamic data obtained during constant flow was compared
      with the c of SOPE fitted to LFI curve (within tidal volume [VT]). Second, the
      dynamic C20/C (ratio of compliance of the last 20% of the curve (C20) to total
      compliance [C]) was compared with the determination of the upper inflection point
      (UIP) on the LFI curve. OD was defined as a negative value of c, a C20/C < 0.80,
      an UIP included within the VT range for that child during regular ventilation.
      Using LFI V-P curves as reference, SOPE offered a better detection of OD than
      dynamic C20/C or the determination of the UIP by graphical means. Indeed the
      first analysis showed a substantial agreement (kappa 0.75) between dynamic c and
      LFI c detection of OD whereas the second analysis showed a poor agreement (kappa
      0.22) between C20/ C and LFI detection of the UIP. In conclusion, quasi-static V
      P curves can easily be obtained in children with the LFI technique. SOPE offers a
      good detection of OD on dynamic and LFI V-P curves but the C20/C index seems to
      be an inadequate measure of OD.

PMID- 10903234
TI  - Increased numbers of dendritic cells in the bronchiolar tissues of diffuse
      panbronchiolitis.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells (APCs); they are
      considered to be the most important APC in the lung. Recently, the number of DCs
      in the large airways was demonstrated to increase in patients with atopic asthma,
      leading to the concept that DCs play an important role in airway inflammation.
      However, little is known about the distribution of lung DCs in the small airways
      under other pathological conditions. The aim of the present study was to examine
      the distribution of DCs in the bronchiolar tissues in patients with diffuse
      panbronchiolitis (DPB), which is a chronic inflammatory disorder of the airways
      histologically characterized by peribronchiolitis. We investigated the
      distribution of DCs in the bronchiolar tissues of the lungs in 11 patients with
      DPB and 7 control subjects with normal lungs using immunohistochemical methods.
      Marked increases in the number of CD1a(+), CD1c(+), and CD83(+) DCs were found in
      both the bronchiolar epithelium and submucosal tissues of patients with DPB,
      compared with control subjects with normal lungs. The most striking increase
      occurred in the number of DCs expressing CD83, a marker of mature DCs, in the
      submucosal tissues of patients with DPB. The increases of these positive cells in
      patients with DPB were more marked in the submucosal tissues than in the
      epithelium. The bronchiolar epithelial cells in patients with DPB strongly
      expressed GM-CSF protein, which is an important cytokine for the differentiation
      and function of DCs, suggesting that the increased local production of GM-CSF may
      be responsible for the accumulation and differentiation of DCs in the bronchiolar
      tissues of patients with DPB. These results suggest that increased DCs in the
      bronchiolar tissues, together with their phenotypical maturation, may play an
      important role in the mucosal immune response in patients with DPB through their
      potent antigen-presenting function.

PMID- 10903235
TI  - Antimicrobial treatment failures in patients with community-acquired pneumonia:
      causes and prognostic implications.
AB  - The aim of the study was to determine the causes and prognostic implications of
      antimicrobial treatment failures in patients with nonresponding and progressive
      life-threatening, community-acquired pneumonia. Forty-nine patients hospitalized
      with a presumptive diagnosis of community-acquired pneumonia during a 16-mo
      period, failure to respond to antimicrobial treatment, and documented repeated
      microbial investigation >/= 72 h after initiation of in-hospital antimicrobial
      treatment were recorded. A definite etiology of treatment failure could be
      established in 32 of 49 (65%) patients, and nine additional patients (18%) had a
      probable etiology. Treatment failures were mainly infectious in origin and
      included primary, persistent, and nosocomial infections (n = 10 [19%], 13 [24%],
      and 11 [20%] of causes, respectively). Definite but not probable persistent
      infections were mostly due to microbial resistance to the administered initial
      empiric antimicrobial treatment. Nosocomial infections were particularly frequent
      in patients with progressive pneumonia. Definite persistent infections and
      nosocomial infections had the highest associated mortality rates (75 and 88%,
      respectively). Nosocomial pneumonia was the only cause of treatment failure
      independently associated with death in multivariate analysis (RR, 16.7; 95% CI,
      1.4 to 194.9; p = 0.03). We conclude that the detection of microbial resistance
      and the diagnosis of nosocomial pneumonia are the two major challenges in
      hospitalized patients with community-acquired pneumonia who do not respond to
      initial antimicrobial treatment. In order to establish these potentially life
      threatening etiologies, a regular microbial reinvestigation seems mandatory for
      all patients presenting with antimicrobial treatment failures.

PMID- 10903236
TI  - Airway inflammation after controlled exposure to diesel exhaust particulates.
AB  - Epidemiologic evidence suggests a link between morbidity and mortality and levels
      of particulate matter in the atmosphere. We studied the inflammatory response to
      inhalation of diesel exhaust particulates (DEP) in normal volunteers. DEP were
      collected from the exhaust of a stationary diesel engine and were resuspended in
      an exposure chamber. Ten nonsmoking healthy volunteers were exposed for 2 h at
      rest to a controlled concentration of DEP (monitored at 200 microg/m(3)
      particulate matter of less than 10 microm aerodynamic diameter [PM(10)]) or air
      in a double-blind, randomized, crossover study. Exposures were followed by serial
      spirometry and measurement of pulse, blood pressure, exhaled carbon monoxide
      (CO), and methacholine reactivity, as well as sputum induction and venesection
      for up to 4 h after exposure, and a repeat of all these procedures at 24 h after
      exposure. There were no changes in cardiovascular parameters or lung function
      following exposure to DEP. Levels of exhaled CO were increased ater exposure to
      DEP, and were maximal at 1 h (air: 2.9 +/- 0.2 ppm [mean +/- SEM]; DEP: 4.4 +/-
      0.3 ppm; p < 0.001). There was an increase in sputum neutrophils and
      myeloperoxidase (MPO) at 4 h after DEP exposure as compared with 4 h after air
      exposure (neutrophils: 41 +/- 4% versus 32 +/- 4%; MPO: 151 ng/ml versus 115
      ng/ml, p < 0.01), but no change in concentrations of inflammatory markers in
      peripheral blood. Exposure to DEPs at high ambient concentrations leads to an
      airway inflammatory response in normal volunteers.

PMID- 10903237
TI  - Respiratory viral infections in adults with and without chronic obstructive
      pulmonary disease.
AB  - A longitudinal cohort study of older adults with chronic obstructive pulmonary
      disease (COPD) who were stratified by FEV(1) at enrollment was done to define the
      etiology, frequency, severity, and medical-care impact of respiratory tract viral
      infections (RTVIs). Controls consisted of a group of subjects of comparable age
      with the patients. RTVIs were documented in 44% of observed acute respiratory
      illnesses in control subjects and in 27% of COPD subjects, who were followed for
      mean periods of 35 and 26 mo, respectively. In this heavily influenza-vaccinated
      cohort ( approximately 90% vaccinated each year), picornaviruses, parainfluenza
      viruses, and coronaviruses were most commonly identified. Mean time to return to
      clinical baseline was approximately 2 wk in each group. Control and COPD subjects
      with mild airways obstruction (baseline FEV(1) >/= 50% predicted) had few
      emergency-center visits or hospitalizations. Approximately half of COPD subjects
      with moderate/severe COPD (baseline FEV(1) < 50% predicted) had at least one
      emergency-center visit and/or hospitalization for acute respiratory illness.
      RTVIs were documented in 23% of hospitalizations and in 45% of patients admitted
      between December and March. RTVIs have a major impact on utilization of health
      care resources for COPD patients with moderate/severe airways obstruction.

PMID- 10903238
TI  - Withdrawal of chronic systemic corticosteroids in patients with COPD: a
      randomized trial.
AB  - The benefits of chronic systemic corticosteroids for patients with chronic
      obstructive pulmonary disease (COPD) are not well established. To determine
      whether chronic corticosteroid treatment can be safely withdrawn in "steroid
      dependent""COPD patients, we performed a double-blind, placebo-controlled study
      of 38 patients with steroid-dependent COPD. Patients were randomly assigned to
      receive their usual maintenance prednisone dose for 6 mo (continuous group) or to
      be withdrawn from prednisone at a rate of 5 mg per week (demand group). The
      number of COPD exacerbations per patient (primary outcome) was 2.5 +/- 2.7 (mean
      +/- SD) in the continuous group and 2.7 +/- 2.5 in the demand group (p = 0.60,
      95% confidence interval for the difference: -1.1 to 1.7). Spirometric results,
      dyspnea, and health-related quality of life did not differ significantly in the
      two groups. The average daily corticosteroid dose was 10.7 +/- 5.2 mg in the
      continuous group and 6.3 +/- 6.4 mg in the demand group (p = 0.003). Weight
      decreased in the demand group by 4.8 +/- 2.0 kg, compared with an increase in the
      continuous group of 0.5 +/- 3.5 kg (p = 0.007). Discontinuation of chronic
      systemic corticosteroid treatment in steroid-dependent COPD patients did not
      cause a significant increase in COPD exacerbations, but did reduce total systemic
      corticosteroid use and body weight. Larger studies may be warranted to establish
      the relative risks and benefits of chronic corticosteroid treatment of patients
      with COPD.

PMID- 10903239
TI  - Effects of cool, dry air stimulation on peripheral lung mechanics in asthma.
AB  - We have previously demonstrated that peripheral airway resistance (Rp) rises more
      in asthmatics than in nonasthmatic control subjects after segmental challenge
      with cool, dry air. To better understand this rise in Rp, we used a stop-flow
      method to measure the decay of segment pressure with time that yielded
      information on airway resistance (Raw), final plateau pressure (Pp), and
      peripheral lung compliance (Cp). After stop-flow maneuvers in all seven
      asthmatics and all seven normal subjects, pressure decayed smoothly without an
      initial sudden drop. This finding suggests that Raw was negligible and that the
      predominant site of flow resistance was the collateral pathways of the obstructed
      segment. Asthmatics had a significantly higher Pp and lower Cp at baseline than
      did normal subjects, but neither Pp nor Cp changed after challenge. Pp and Rp
      were significantly correlated. When interpreted in terms of a single-compartment
      nonlinear model, we concluded that Rp is predominantly determined by the
      resistance of the collateral airways rather than the more proximal airways. We
      also concluded that, compared with normal subjects, asthmatics have (1) more
      collateral airway narrowing and closure and lower segmental compliance, and (2)
      after challenge, increased collateral airway narrowing or closure without a
      change in compliance of the distal lung parenchyma. These results reflect the
      fundamental differences in peripheral lung mechanics between asthmatic and
      nonasthmatic subjects and in their response to directly instilled cool, dry air.

PMID- 10903240
TI  - Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool
      children.
AB  - We hypothesized that a leukotriene receptor antagonist (LTRA) could provide
      bronchoprotection against the cold, dry air-induced response in asthmatic
      preschool children. In a randomized, double-blind, placebo-controlled crossover
      study, we examined the effect of the specific LTRA montelukast at 5 mg/d for 2 d
      on the bronchoconstriction induced by hyperventilation of cold, dry air in 13
      asthmatic children 3 to 5 yr old. The bronchoconstriction was measured as the
      specific airway resistance (sRaw) in a whole-body plethysmograph before and 4 min
      after challenge with cold, dry air. The repeatability of the bronchoprotection
      was examined by repeating the placebo-controlled study in six of the 13 children.
      sRaw increased by an average of 46% (95% confidence interval [CI]: 30 to 63%)
      after placebo treatment and 17% (95% CI: 3 to 31%) after montelukast (p < 0.01).
      Eight of the children were receiving regular treatment with budesonide delivered
      by an inhaler with a spacer in a mean daily dose of 350 microg, but the
      bronchoprotection provided by montelukast was independent of concurrent steroid
      treatment. There was no convincing evidence of failure to respond, and the
      protective effect of montelukast was consistent upon repeated testing (p = 0.
      02). We conclude that the LTRA montelukast provided clinically significant
      bronchoprotection against the effect of hyperventilation of cold dry air in
      asthmatic children 3 to 5 yr old. The bronchoprotection appeared to be
      homogeneous among the children, and seemed independent of steroid treatment. This
      suggests that LTRAs may be of therapeutic use in limiting clinical symptoms of
      asthma in young children.

PMID- 10903241
TI  - Hemodynamic tolerance of intermittent hemodialysis in critically ill patients:
      usefulness of practice guidelines.
AB  - Poor hemodynamic tolerance of intermittent hemodialysis (IHD) is a common problem
      for patients in an intensive care unit (ICU). New dialysis strategies have been
      adapted to chronic hemodialysis patients with cardiovascular insufficiency. To
      improve hemodynamic tolerance of IHD, specific guidelines were progressively
      implemented into practice through the year 1996 in our 26-bed medical ICU. To
      evaluate the efficiency of these guidelines we retrospectively compared all IHD
      performed during the years before (1995) and after (1997) implementation of these
      recommendations. Forty-five patients underwent 248 IHD sessions in 1995 and 76
      patients underwent 289 IHD sessions in 1997. The two populations were similar for
      age, sex, chronic hemodialysis (26% versus 17%), and secondary acute renal
      failure. In 1997, patients were more severely ill with a higher SAPS II (50 +/-
      17 versus 59 +/- 24; p = 0.036), and more patients required epinephrine or
      norepinephrine infusion before dialysis sessions (16% versus 34%; p < 0.0001).
      The compliance to guidelines was high, inducing a significant change in IHD
      modalities. As a result, hemodynamic tolerance was significantly better in 1997,
      with less systolic blood pressure drop at onset (33% versus 21%, p = 0. 002) and
      during the sessions (68% versus 56%, p = 0.002). IHD with hypotensive episode or
      need for therapeutic interventions were less frequent in 1997 (71% versus 61%, p
      = 0.015). The ICU mortality was similar (53.3% in 1995 versus 47.3% in 1997; p =
      0.52) but death rate in 1997, but not in 1995, was significantly less than
      predicted from SAPS II (47.3% versus 65.6%; p = 0.02). Length of ICU stay was
      also reduced for survivors in 1997 (p = 0.04). Implementation of practice
      guidelines for intermittent hemodialysis in ICU patients lessens hemodynamic
      instability and may improve outcome.

PMID- 10903242
TI  - Ventilatory and respiratory muscle responses to hypercapnia in patients with
      paraplegia.
AB  - To evaluate ventilatory and respiratory muscle responses to hypercapnia in
      patients with paraplegia with paralysis of abdominal muscles, we studied seven
      patients with complete transection of the midthoracic cord (Th6-Th7) and six
      normal subjects. Minute ventilation (V E) and mean inspiratory flow responses to
      hypercapnia were similar in normal subjects and patients with paraplegia, but in
      the latter, at any given level of end-tidal CO(2) partial pressure (PET(CO(2))),
      tidal volume (VT) was reduced and frequency was increased. In normal subjects
      during hypercapnia, end-expiratory transpulmonary pressure (PL) and abdominal
      volume at end expiration decreased markedly, whereas end-expiratory volume of the
      rib cage (Vrc,E) remained constant, suggesting progressive recruitment of
      abdominal muscles. In patients with paraplegia compared to normal subjects the
      decrease in end-expiratory PL was reduced, and it was associated with a decrease
      in Vrc,E, suggesting recruitment of rib cage expiratory muscles. For a PET(CO(2))
      of 70 mm Hg the estimated expiratory muscle contribution to VT was 10.3 and 28.4%
      (p < 0.02) in patients with paraplegia and normal subjects, respectively. We
      conclude that the V E-CO(2) relationship is preserved in patients with paraplegia
      with the development of a rapid and shallow pattern of breathing. This suggests
      that expiratory muscle paralysis elicits adaptation of the ventilatory control
      system similar to that observed in patients with generalized respiratory muscle
      weakness.

PMID- 10903243
TI  - Permissive hypercapnia impairs pulmonary gas exchange in the acute respiratory
      distress syndrome.
AB  - Current recommendations for mechanical ventilation in the acute respiratory
      distress syndrome (ARDS) include the use of small tidal volumes (VT), even at the
      cost of respiratory acidosis. We evaluated the effects of this permissive
      hypercapnia on pulmonary gas exchange with the multiple inert gas elimination
      technique (MIGET) in eight patients with ARDS. After making baseline
      measurements, we induced permissive hypercapnia by reducing VT from 10 +/- 2
      ml/kg to 6 +/- 1 ml/kg (mean +/- SEM) at constant positive end-expiratory
      pressure. After restoration of initial VT, we infused dobutamine to increase
      cardiac output (Q) by the same amount as with hypercapnia. Permissive hypercapnia
      increased Q by an average of 1.4 L. min(-)(1). m(2), decreased arterial oxygen
      tension from 109 +/- 10 mm Hg to 92 +/- 11 mm Hg (p < 0.05), markedly increased
      true shunt (Q S/Q T), from 32 +/- 6% to 48 +/- 5% (p < 0.0001), and had no effect
      on the dispersion of VA/Q.VA/Q. On reinstatement of baseline V T with maintenance
      of a high Q, Q S/Q T remained increased, to 38 +/- 6% (p < 0.05), and Pa(O(2
      ))remained decreased, to 93 +/- 4 mm Hg (p < 0. 05). These results agreed with
      effects of changes in VT and Q predicted by the mathematical lung model of the
      MIGET. We conclude that permissive hypercapnia increases pulmonary shunt, and
      that deterioration in gas exchange is explained by the combined effects of
      increased Q and decreased alveolar ventilation.

PMID- 10903244
TI  - Factor analysis of changes in dyspnea and lung function parameters after
      bronchodilation in chronic obstructive pulmonary disease.
AB  - Expiratory airway collapse is a characteristic feature in patients with chronic
      obstructive pulmonary disease (COPD). We hypothesized that this collapse might
      mask the effects of bronchodilators during forced expiration but not during
      forced inspiration, and that accordingly, the improvement in forced inspiration
      and not that in forced expiration with bronchodilator therapy would be related to
      changes in the perception of dyspnea. In order to investigate this, we conducted
      lung function measurements, including measurements of forced inspiration and
      expiration before and 30 min after inhalation of 400 microg salbutamol, in 61
      patients with COPD (mean FEV(1): 38. 3 L; range: 12.9 to 79.5% predicted). The
      change in dyspnea from baseline was assessed with a standard visual analogue
      scale (VAS) ranging from -100 to +100. To delineate the relationship between
      parameters, we used the statistical procedure of factor analysis. Salbutamol
      induced an improvement of 0.16 +/- 0.02 L (mean +/- SD) in FEV(1), 0.36 +/- 0.04
      L in forced inspiratory volume in one second (FIV(1)), 0.30 +/- 0.04 L in
      inspiratory capacity (IC), and -0.34 +/- 0.07 L in intrathoracic gas volume; the
      mean VAS score was 36.4 +/- 3.2. Factor analysis demonstrated that the reduction
      in dyspnea at rest was primarily associated with changes in parameters describing
      forced inspiration and not with those of forced expiration or lung
      hyperinflation, including IC. Our data indicate that in patients with COPD, the
      reduction in dyspnea after inhalation of a beta(2)-adrenoreceptor agonist is
      closely correlated with the change in parameters of forced inspiration, and
      particularly FIV(1), but not with changes in parameters of forced expiration or
      lung hyperinflation.

PMID- 10903245
TI  - Exhaled nitric oxide in high-altitude pulmonary edema: role in the regulation of
      pulmonary vascular tone and evidence for a role against inflammation.
AB  - High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in
      predisposed subjects at altitudes above 2,500 m. It is not clear whether, in
      addition to hemodynamic factors and defective alveolar fluid clearance,
      inflammation plays a pathogenic role in HAPE. We therefore made serial
      measurements of exhaled pulmonary nitric oxide (NO), a marker of airway
      inflammation, in 28 HAPE-prone and 24 control subjects during high-altitude
      exposure (4,559 m). To examine the relationship between pulmonary NO synthesis
      and pulmonary vascular tone, we also measured systolic pulmonary artery pressure
      (Ppa). In the 13 subjects who developed HAPE, exhaled NO did not show any
      tendency to increase during the development of lung edema. Throughout the entire
      sojourn at high altitude, pulmonary exhaled NO was roughly 30% lower in HAPE
      prone than in control subjects, and there existed an inverse relationship between
      Ppa and exhaled NO (r = -0.51, p < 0.001). These findings suggest that HAPE is
      not preceded by airway inflammation. Reduced exhaled NO may be related to altered
      pulmonary NO synthesis and/or transport and clearance, and the data in our study
      could be consistent with the novel concept that in HAPE-prone subjects, a defect
      in pulmonary epithelial NO synthesis may contribute to exaggerated hypoxic
      pulmonary vasoconstriction and in turn to pulmonary edema.

PMID- 10903246
TI  - Aerosolized administration of N-acetylcysteine attenuates lung fibrosis induced
      by bleomycin in mice.
AB  - Reactive oxygen species (ROS) play an important role in the pathogenesis of
      pulmonary fibrosis. We previously demonstrated that N-acetylcysteine (NAC), an
      antioxidant, inhibited adhesion molecule expression and cytokine production in
      lung cells. When NAC is inhaled into the alveolar space, it is expected to
      directly interact with inflammatory cells and to elevate glutathione levels in
      the epithelial lining fluids. We therefore examined whether inhaled NAC inhibits
      lung fibrosis induced by bleomycin (BLM). Male ICR mice were given a single
      intravenous injection of BLM (150 mg/ kg). Thirty milliliters of NAC (70 mg/ml)
      or saline were inhaled twice a day for 28 d using an ultrasonic nebulizer. In the
      inflammatory phase (Day 7), NAC administration attenuated the cellular
      infiltration in both bronchoalveolar lavage fluid (BALF) and alveolar tissues. At
      Day 28, the fibrotic changes estimated by Aschroft's criteria and hydroxyproline
      content in the NAC inhalation group were significantly decreased compared with
      the BLM-only group (p < 0.05). CXC chemokines, macrophage inflammatory protein-2
      (MIP-2), cytokine-induced neutrophil chemoattractant (KC), and CC chemokines,
      macrophage inflammatory protein-1alpha (MIP-1alpha), in BALF were mostly elevated
      on Day 7 in the BLM-only group; however, these elevations were significantly
      repressed by NAC inhalation (p < 0.05). Lipid hydroperoxide (LPO) was also
      quantified in BALF. LPO was markedly increased on Day 3 in the BLM-only group,
      and this increase was significantly decreased by NAC inhalation (p < 0.05). These
      results revealed that aerosolized NAC ameliorated acute pulmonary inflammation
      induced by BLM injection via the repression of chemokines and LPO production,
      resulting in the attenuation of subsequent lung fibrosis. These findings are
      limited to the BLM-induced lung fibrosis animal model. However, NAC inhalation
      will be expected to be a potential therapy for patients with other interstitial
      pneumonias because ROS are involved in the pathogenesis of lung injury in most
      interstitial pneumonia.

PMID- 10903247
TI  - Synthetic oligodeoxynucleotides inhibit IgE induction in human lymphocytes.
AB  - Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs have
      the capacity to stimulate T-helper (Th)1-type responses in mice. Th1 cytokines
      are known to act as downregulators of IgE production. In this study we
      investigated whether synthetic ODNs inhibited IgE production in human peripheral
      blood mononuclear cells (PBMC) from normal donors stimulated with interleukin
      (IL)-4 plus anti-CD40 monoclonal antibody (mAb) in vitro. Thirty-mer single
      stranded ODNs were randomly selected from the complementary DNA encoding the MPB
      70 of Mycobacterium bovis Bacillus Calmette-Guerin. Two ODNs, containing CGTACG
      or AACGTT inhibited IgE production by human PBMC. When other oligonucleotides
      were substituted in a portion of the sequence of the core or flanking
      oligonucleotides in the ODN containing CGTACG, ODNs containing NACGTTCG or
      A/CTCGTTCG sequences specifically inhibited IgE production by human PBMC in
      vitro. The inhibition of IgE production by certain ODNs was mediated by both
      interferon (IFN)-gamma and IL-12, since the ODN-induced suppression was blocked
      by the addition of anti-IFN-gamma or anti-IL-12 mAb. Also, the ODNs inhibited
      induction of epsilon germline transcripts by IL-4. Our findings indicate that
      synthetic ODNs appear to be candidates for the treatment of IgE-dependent
      allergic disease in humans.

PMID- 10903248
TI  - Adductor pollicis twitch tension assessed by magnetic stimulation of the ulnar
      nerve.
AB  - Many critically ill patients develop significant skeletal muscle weakness in the
      Intensive Care Unit (ICU), which ultimately may cause difficulties in weaning
      from mechanical ventilation and a protracted, expensive ICU stay. Reliable
      monitoring of muscle strength in this environment is difficult. The purpose of
      this study was to develop a reproducible, nonvolitional method of measuring
      adductor pollicis (AP) muscle function by magnetic stimulation of the ulnar nerve
      (MSUN) that could be applied to patients in the ICU and operating theater (OT).
      Fifty subjects (32 healthy control subjects [12 of whom were elderly], 12 ICU
      patients with critical illness [mean APACHE II score 20], and six otherwise
      healthy patients requiring minor surgery in the OT) received MSUN. In 12 of the
      normal subjects electrical stimulation of the ulnar nerve (ESUN) and MSUN were
      compared and AP twitch tension (Tw AP) and surface electromyogram (EMG) were
      measured. Close agreement was found between supramaximal Tw AP (median [95% CI]
      for MSUN 6.3 N [5-7.2 N] and ESUN 6.9 N [5.2-7.8 N] [p = NS]). Median (95% CI)
      values with MSUN for the 20 young and 12 elderly control subjects were 6.9 N (5.
      3-7.4 N) and 7.1 N (4.4-9.8 N). Median (95% CI) Tw AP for the ICU group was 4.2
      (2.2-6.7 N) and for the OT group was 5.8 (4-9.1 N). Tw AP was significantly
      reduced in ICU patients compared with age-matched controls (p = 0.01). MSUN can
      be used to measure neuromuscular function in both the laboratory and clinical
      settings including the ICU.

PMID- 10903249
TI  - A randomized, controlled crossover trial of two oral appliances for sleep apnea
      treatment.
AB  - Our purpose was to compare the effectiveness and side effects of a novel, single
      piece mandibular advancement device (OSA-Monobloc) for sleep apnea therapy with
      those of a two-piece appliance with lateral Herbst attachments (OSA-Herbst) as
      used in previous studies. An OSA-Monobloc and an OSA-Herbst with equal protrusion
      were fitted in 24 obstructive sleep apnea patients unable to use continuous
      positive airway pressure (CPAP) therapy. After an adaptation period of 156 +/- 14
      d (mean +/- SE), patients used the OSA-Monobloc, the OSA-Herbst, and no appliance
      in random order, using each appliance for 1 wk. Symptom scores were recorded and
      sleep studies were done at the end of each week. Several symptom scores were
      significantly improved with both appliances, but to a greater degree with the OSA
      Monobloc. Epworth Sleepiness Scale scores were 8.8 +/- 0.7 with the OSA-Herbst,
      and 8.6 +/- 0.8 with the OSA-Monobloc devices, and 13.1 +/- 0.9 without therapy
      (p < 0.05 versus both appliances). The apnea/hypopnea index was 8.7 +/- 1.5/h
      with the OSA-Herbst and 7.9 +/- 1.6/h with the OSA-Monobloc device, and 22.6 +/-
      3.1/h without therapy (p < 0.05 versus both appliances). Side effects were mild
      and of equal prevalence with both appliances. Fifteen patients preferred the OSA
      Monobloc, eight patients had no preference, and one patient preferred the OSA
      Herbst device (p < 0.008 versus OSA-Monobloc). We conclude that both the OSA
      Herbst and the OSA-Monobloc are effective therapeutic devices for sleep apnea.
      The OSA-Monobloc relieved symptoms to a greater extent than the OSA-Herbst, and
      was preferred by the majority of patients on the basis of its simple application.

PMID- 10903250
TI  - Nasal continuous positive airway pressure reduces sleep-induced blood pressure
      increments in preeclampsia.
AB  - Preeclampsia is the predominant cause of admissions to neonatal intensive care.
      The diurnal blood pressure pattern is flattened or reversed in preeclampsia. We
      hypothesized that snoring and partial upper airway obstruction contribute to
      nocturnal rises in blood pressure. We tested this hypothesis by controlling sleep
      induced upper airway flow limitation and snoring with nasal positive pressure.
      Eleven women with preeclampsia underwent two consecutive polygraphic sleep
      studies with simultaneous beat-to-beat blood pressure monitoring. Average blood
      pressure for the night overall and in each sleep stage was calculated. Sleep
      architecture was similar on the two study nights. Sleep-induced partial upper
      airway flow limitation occurred in all patients in the initial study. Autosetting
      nasal continuous positive airway pressure (CPAP) applied at a mean maximal
      pressure of 6 +/- 1 cm H(2)O eliminated flow limitation throughout sleep on the
      treatment night. Blood pressure was markedly reduced on the treatment night [(128
      +/- 3)/(73 +/- 3)] when compared with the initial nontreatment study night [(146
      +/- 6)/(92 +/- 4)], p = (0.007)/(0.002). We conclude that partial upper airway
      obstruction during sleep in women with preeclampsia is associated with increments
      in blood pressure, which can be eliminated with the use of nasal CPAP.

PMID- 10903251
TI  - Serum levels of surfactant proteins A and D are useful biomarkers for
      interstitial lung disease in patients with progressive systemic sclerosis.
AB  - To find a less-invasive and lung-specific clinical biomarker, we measured serum
      levels of surfactant proteins A and D (SP-A and SP-D) by sandwich enzyme-linked
      immunosorbent assays in 42 patients with progressive systemic sclerosis (PSS) to
      evaluate their significance in relation to the presence of interstitial lung
      disease (ILD) and to assess their diagnostic merits. The patients were divided
      into two groups based on findings by chest computed tomography (CT): 30 patients
      with ILD (CT-positive ILD group), and 12 patients without any lung abnormalities
      (CT-negative ILD group). The CT-positive ILD group was further divided into two
      groups: 24 patients with ILD detectable by chest plain radiography (X-ray
      positive ILD group) and six patients with ILD showing no abnormality (X-ray
      negative ILD group). The levels of SP-A and SP-D in sera were significantly
      higher in the CT-positive ILD group than in the CT-negative ILD group. They were
      also significantly higher in the X-ray-positive ILD group than in the CT-negative
      ILD group. In the X-ray-negative ILD group, their levels were higher than those
      of the CT-negative ILD group. We next estimated sensitivity and specificity of SP
      A, SP-D, and X-ray for detecting ILD on CT. Sensitivity of SP-D was high (77%) as
      well as that of X-ray (80%), whereas SP-A showed a low sensitivity (33%).
      Remarkably, five of six patients in the X-ray-negative ILD group showed SP-D
      concentrations over its cut-off level, thereby demonstrating that an SP-D assay
      contributes to the detection of ILD overlooked by X-ray. Moreover, a combination
      of X-ray and SP-D dramatically increases sensitivity to 97%. Specificity of SP-A,
      SP-D, and X-ray to the CT-negative ILD group was 100%, 83%, and 100%,
      respectively. In conclusion, this study indicates that elevated levels of serum
      SP-A and SP-D reflect well the presence of ILD and that the combination of SP-D
      and X-ray contributes to reduce the risk of clinicians overlooking ILD
      complicated by PSS, although a repetition in another set of subjects is needed to
      confirm these indications.

PMID- 10903252
TI  - Is high-resolution computed tomography a reliable tool to predict the
      histopathological activity of pulmonary Langerhans cell histiocytosis?
AB  - High-resolution computed tomography (HRCT) has proved to be very useful in the
      diagnosis and follow-up of pulmonary Langerhans cell histiocytosis (PLCH), but
      the precise relationships between nodules and thin-wall cysts observed by HRCT,
      and granulomatous or cystic lesions present in lung tissue, remain to be
      established. The aim of this study was to compare quantitative data obtained by
      HRCT and those obtained by histopathological examination of corresponding lung
      tissue specimens in patients with biopsy-proven PLCH. The results demonstrated
      that the extent of nodular abnormalities was strongly correlated with the density
      of florid granulomatous lesions in lung tissue. A strong correlation was also
      found between the extent of cystic abnormalities and the density of cavitary
      lesions, but the latter included both still inflammatory cavitary granulomas and
      cicatricial fibrous cysts. Interestingly, small isolated florid granulomas were
      found in lung tissue from most patients with a predominant cystic CT scan
      pattern. Taken together, these results demonstrate that HRCT has to be considered
      with caution to evaluate the histopathological activity of PLCH. Patients
      presenting with predominant HRCT cystic abnormalities should benefit from a long
      term follow-up. Because these patients are susceptible to developing severe
      respiratory insufficiency, they should also be considered for treatment as soon
      as an effective therapy for LCH is available.

PMID- 10903253
TI  - Effect of partial liquid ventilation on pulmonary vascular permeability and edema
      after experimental acute lung injury.
AB  - We evaluated the effects of partial liquid ventilation (PLV) with two different
      dosages of the perfluorocarbon LiquiVent (perflubron) on pulmonary vascular
      permeability and edema formation after oleic acid (OA)-induced acute lung injury
      in dogs. We used imaging with positron emission tomography to measure fractional
      pulmonary blood flow, lung water concentration (LWC), and the pulmonary
      transcapillary escape rate (PTCER) of (68)Ga-labeled transferrin at 5 and 21 h
      after lung injury in five dogs undergoing conventional mechanical ventilation
      (CMV), five dogs undergoing low-dose PLV (perflubron at 10 ml/kg), and four dogs
      undergoing high dose PLV (perflubron at 30 ml/kg). A positive end-expiratory
      pressure of 7.5 cm H(2)O was used in all dogs. After OA (0.08 ml/kg)- induced
      lung injury, there were no significant differences or trends for PTCER or LWC at
      any time when the PLV groups were compared with the CMV group. However, lung
      tissue myeloperoxidase activity was significantly lower in the combined PLV group
      than in the CMV group (p = 0.016). We conclude that after OA-induced lung injury,
      the addition of PLV to CMV does not directly attenuate pulmonary vascular leak or
      lung water accumulation. Rather, the benefits of such treatment may be due to
      modifications of the inflammatory response.

PMID- 10903254
TI  - Severe mechanical dysfunction in pharyngeal muscle from adult mdx mice.
AB  - The mdx mouse is a widely used animal model of human muscular dystrophy. Although
      diaphragm muscle exhibits severe muscle weakness throughout the life of the
      animal, the limb muscle function of mdx mice spontaneously recovers by 6 mo of
      age. Pharyngeal dilator muscles such as sternohyoid (SH) contribute to upper
      airway patency during breathing. We hypothesized that SH muscle function was
      impaired in 6-mo-old mdx mice. Mechanical properties and myosin heavy chain (MHC)
      composition were investigated in isolated SH from 6-mo-old control (C, n = 10)
      and mdx (n = 10) mice. As compared with C, peak tetanic tension (Pmax) and
      maximum shortening velocity were 50% and 16% lower in mdx mice (p < 0.001 and p <
      0.05, respectively). Peak mechanical power was lower in mdx than in C (19.0 +/-
      3.2 versus 57.4 +/- 5.1 mW g(-)(1), p < 0.001). Both C and mdx SH were composed
      exclusively of fast myosin isoforms. As compared with C, mdx SH presented a
      higher proportion of IIX-MHC and a reduction in IIB-MHC (each p < 0.001). In
      conclusion, our results demonstrated severe SH muscle dysfunction in 6-mo-old mdx
      mice, that is, at a time when limb muscle function has recovered. Thus, SH muscle
      of the mdx mouse may be an excellent muscle for studying Duchenne muscular
      dystrophy.

PMID- 10903255
TI  - beta-adrenergic stimulation restores rat lung ability to clear edema in
      ventilator-associated lung injury.
AB  - Mechanical ventilation with high tidal volume (HVT) causes lung injury and
      decreases the lung's ability to clear edema in rats. beta-adrenergic agonists
      increase active Na(+) transport and lung edema clearance in normal rat lungs by
      stimulating apical Na(+) channels and basolateral Na,K-ATPase in alveolar
      epithelial cells. We studied whether beta-adrenergic agonists could restore lung
      edema clearance in rats ventilated with HVT (40 ml/kg, peak airway pressure of 35
      cm H(2)O) for 40 min. The ability of rat lungs to clear edema decreased by
      approximately 50% after 40 min of HVT ventilation. Terbutaline (TERB) and
      isoproterenol (ISO) increased lung edema clearance in control nonventilated rats
      (from 0.50 +/- 0. 02 ml/h to 0.81 +/- 0.04 ml/h and 0.99 +/- 0.05 ml/h,
      respectively) and restored the lung's ability to clear edema in HVT ventilated
      rats (from 0.25 +/- 0.03 ml/h to 0.64 +/- 0.02 ml/h and 0.88 +/- 0. 09 ml/h,
      respectively). Disruption of cell microtubular transport system by colchicine
      inhibited the stimulatory effects of ISO in HVT ventilated rats, whereas beta
      lumicolchicine did not affect beta-adrenergic stimulation. The Na,K-ATPase
      alpha(1)- and beta(1)-subunit mRNA steady state levels were not affected by
      incubation with ISO for 60 min in alveolar type II cells isolated from control
      and HVT ventilated rats. The data suggest that beta-adrenergic agonists increased
      alveolar fluid reabsorption in rats ventilated with HVT by promoting recruitment
      of ion-transporting proteins from intracellular pools to the plasma membrane of
      alveolar epithelial cells.

PMID- 10903256
TI  - Actin-containing sera from patients with adult respiratory distress syndrome are
      toxic to sheep pulmonary endothelial cells.
AB  - Actin released from damaged cells after a variety of tissue injuries appears to
      be involved in multiple organ dysfunction syndrome. Under experimental
      conditions, when the quantity of actin present in plasma is made to exceed the
      protective capacity of the actin-scavenging mechanism, microembolism and
      pulmonary vascular angiopathy have been noted in rats. It remains to be
      determined whether this injury is a result of a direct toxic effect or occurs
      indirectly via platelet activation or fibrin interactions. We examined the effect
      of sera from patients with adult respiratory distress syndrome (ARDS), as well as
      G-actin added to normal serum, on the viability, morphology, and function of
      cultured sheep pulmonary artery endothelial cells (SPAEC). Both patient sera and
      normal sera to which actin was added were toxic in the cell culture model; this
      toxicity could be abrogated, at least partially, by preincubation with gelsolin,
      which is known to complex with actin. A significant portion of the toxicity of
      sera from patients with ARDS was sensitive to heat (56 degrees C), suggesting an
      important role of complement. Sera from patients with ARDS were shown to contain
      filaments of F-actin by immunoblot and rhodamine phalloidin staining after
      ultracentrifugation. Thus, saturation of the actin-scavenging system by addition
      of exogenous G-actin to plasma produces direct pulmonary endothelial cell injury.
      Furthermore, plasma from patients with ARDS secondary to bacterial pneumonia is
      toxic to SPAEC, and a small but significant contributory role of actin is
      apparent in these studies.

PMID- 10903257
TI  - Pneumoconiosis-related lung cancers: preferential occurrence from diffuse
      interstitial fibrosis-type pneumoconiosis.
AB  - It has been reported that patients with pneumoconiosis occasionally have a
      diffuse interstitial fibrosis (DIF) that resembles interstitial pneumonia, but
      little is known about the relation between pneumoconiosis-associated DIF and the
      risk of lung cancer. In the present study, we evaluated the incidence of DIF by
      chest CT and its contribution to lung cancer in 563 patients with nonasbestos
      pneumoconiosis. Fifty-five (10%) of the 563 patients had DIF. Pneumoconiosis with
      DIF had an exceedingly high concurrence of lung cancers when compared with
      pneumoconiosis without DIF (29 [53%] of 55 versus 78 [15%] of 508, p < 0.001).
      Squamous cell carcinomas (SCCs) of the lung from pneumoconiosis with DIF
      exclusively comprised peripheral-types, as compared with SCCs from pneumoconiosis
      without DIF (13 [100%] of 13 versus 33 [72%] of 46, p = 0.03). In addition, lung
      cancers arose frequently from the area of DIF in pneumoconiosis with DIF (20
      [74%] of 27). Furthermore, our pathologic examination revealed that dysplasias
      from pneumoconiosis with DIF were significantly more frequently observed in
      peripheral bronchioli than were dysplasias from pneumoconiosis without DIF (11
      [69%] of 16 versus 20 [30%] of 66, p = 0.01). p53 expression evaluated by
      immunohistochemistry was frequently observed in dysplasias from pneumoconiosis
      with DIF, although it was not significantly different compared with that in
      dysplasias from pneumoconiosis without DIF (5 [50%] of 10 versus 12 [38%] of 32).
      Taken together, these results may suggest a positive causal relationship between
      pneumoconiosis and peripheral-type SCCs of the lung, and further indicate a
      pivotal role of diffuse fibrosis for the excess incidence of lung cancers,
      especially peripheral-type SCCs, in DIF-type pneumoconiosis.

PMID- 10903258
TI  - Airway complications following pediatric lung and heart-lung transplantation.
AB  - Obstruction at the airway anastomosis is a recognized complication of adult heart
      lung transplantation (HLT) and lung transplantation (LT). Data for pediatric
      transplantation have been scarce. We reviewed our experience in pediatric HLT and
      LT to determine the frequency of airway complications and to document the
      therapeutic modalities used for their treatment. Fifty-three patients (median
      age: 13.8 yr; range: 1.3 to 28.2 yr) underwent HLT (n = 25), SLT (n = 3), DLT (n
      = 25), or repeat DLT (n = 3) and survived for more than 72 h. Major anastomotic
      airway complications requiring intervention affected one of the 25 HLT (4%) and
      seven of the 28 LT (SLT + DLT) patients (25%) (p = 0.05). Four patients with
      granulation tissue occluding the airway were treated with forceps resection,
      laser ablation, or balloon dilatation. Three patients with fibrotic strictures
      received silicone stents, laser ablation, or balloon dilatation. Two patients
      with bronchomalacia or diffuse stricture below the anastomosis underwent metal
      stent placement. Five of seven patients who were treated for anastomotic
      complications had satisfactory relief of airway obstruction. As compared with
      previously studied adults, pediatric heart-lung transplant recipients had the
      same or a lower frequency, and pediatric lung transplant recipients had a higher
      frequency of major anastomotic airway complications. A variety of treatment
      modalities were necessary to achieve adequate relief of airway obstruction.

PMID- 10903259
TI  - Targeting the angiotensin system in posttransplant airway obliteration: the
      antifibrotic effect of angiotensin converting enzyme inhibition.
AB  - The angiotensin system plays a role in the pathogenesis of fibrotic diseases. We
      used a rat heterotopic tracheal transplant model of bronchiolitis obliterans (BO)
      to examine the role of angiotensin converting enzyme (ACE) in development of the
      fibroproliferative lesion of BO. Isograft and allograft tracheal transplants were
      performed. Allograft rats received either no treatment (control) or captopril
      (100 mg/kg/d) in their drinking water. The drug treatment given to the recipient
      rats was begun 5 days before transplantation, on postoperative Day 1, or on
      postoperative Day 5. The treatment was continued until postoperative Day 21, when
      tracheal specimens were harvested and subjected to histologic, immunohistologic,
      and morphometric analyses. We noted heavy staining for ACE in the obliterated
      portion of the tracheas of allograft control animals. This area was not present
      in nontransplanted or isograft tracheas. Captopril administration begun 5 d
      before transplantation and on postoperative Day 1 resulted in a significant
      attenuation in the percent airway obliteration (45% and 26%, respectively) as
      compared with that in control allografts (83%; p < 0.05). This study demonstrates
      the presence of ACE in the fibroproliferative lesion in a rat model of BO, and
      shows that inhibition of ACE can limit development of airway obliteration.

PMID- 10903260
TI  - Specific HLA in pulmonary MAC infection in a Japanese population.
AB  - Patients with pulmonary Mycobacterium avium complex (MAC) infection occasionally
      have neither past histories of pulmonary diseases nor underlying immunodeficiency
      conditions. Therefore, we hypothesized that MAC may be linked with a disease
      susceptibility gene and determined human leukocyte-associated antigens (HLA) in
      patients with pulmonary MAC infection. HLA phenotypes were tested in 59 patients
      with pulmonary MAC infection, and diagnosed according to the criteria of the
      American Thoracic Society. Data of a Japanese population reported at the Tenth
      Japan HLA Workshop were used as a control. HLA-A33 (28.8% versus 12.5%, p = 5 x
      10(-)(4)) and HLA-DR6 (50.8% versus 20.2%, p = 5 x 10(-)(8)) antigen frequencies
      in patients with MAC were significantly increased compared with those of the
      control population. Frequency of a haplotype A33-B44-DR6 in the MAC patients was
      also significantly increased compared with those of the control population (23.7%
      versus 4.2%; p = 3 x 10(-)(9)). These data suggest that development of pulmonary
      MAC infection is associated with specific HLA in a Japanese population.

PMID- 10903261
TI  - Biologically variable or naturally noisy mechanical ventilation recruits
      atelectatic lung.
AB  - Biologically variable mechanical ventilation (Vbv)-using a computer-controller to
      mimic the normal variability in spontaneous breathing-improves gas exchange in a
      model of severe lung injury (Lefevre, G. R., S. E. Kowalski, L. G. Girling, D. B.
      Thiessen, W. A. C. Mutch. Am. J. Respir. Crit. Care Med. 1996;154:1567-1572).
      Improved oxygenation with Vbv, in the face of alveolar collapse, is thought to be
      due to net volume recruitment secondary to the variability or increased noise in
      the peak inspiratory airway pressures (Ppaw). Biologically variable noise can be
      modeled as an inverse power law frequency distribution (y approximately 1/f(a))
      (West, B. J., M. Shlesinger. Am. Sci. 1990;78:40-45). In a porcine model of
      atelectasis-right lung collapse with one-lung ventilation-we studied if Vbv (n =
      7) better reinflates the collapsed lung compared with conventional monotonously
      regular control mode ventilation (Vc; n = 7) over a 5-h period. We also
      investigated the influence of sigh breaths with Vc (Vs; n = 8) with this model.
      Reinflation of the collapsed lung was significantly enhanced with Vbv-greater
      Pa(O(2)) (502 +/- 40 mm Hg with Vbv versus 381 +/- 40 mm Hg with Vc at 5 h; and
      309 +/- 79 mm Hg with Vs; mean +/- SD), lower Pa(CO(2)) (35 +/- 4 mm Hg versus 48
      +/- 8 mm Hg and 50 +/- 8 mm Hg), lower shunt fraction (9.7 +/- 2.7% versus 14.6
      +/- 2.0% and 22.9 +/- 6.0%), and higher respiratory system compliance (Crs) (1.15
      +/- 0.15 ml/cm H(2)O/kg versus 0.79 +/- 0.19 ml/cm H(2)O/kg and 0.77 +/- 0.13
      ml/cm H(2)O/kg)-at lower mean Ppaw (15.7 +/- 1.4 cm H(2)O versus 18.8 +/- 2.3 cm
      H(2)O and 18.9 +/- 2.8 cm H(2)O). Vbv resulted in an 11% increase in measured
      tidal volume (VT(m)) over that seen with Vc by 5 h (14.7 +/- 1.2 ml/kg versus 13.
      2 ml/kg). The respiratory rate variability programmed for Vbv demonstrated an
      inverse power law frequency distribution ( y approximately 1/f(a)) with a = 1.6
      +/- 0.3. These findings provide strong support for the theoretical model of noisy
      end-inspiratory pressure better recruiting atelectatic lung. Our results suggest
      that using natural biologically variable noise has enhanced the performance of a
      mechanical ventilator in control mode.

PMID- 10903262
TI  - Availability of an alcohol solution can improve hand disinfection compliance in
      an intensive care unit.
AB  - We investigated whether rubbing with an alcohol solution increases compliance
      with hand disinfection in a medical intensive care unit (MICU). During a first
      period (P1), hand disinfection was achieved only through conventional washing,
      whereas during a second period (P2), hand disinfection could be achieved either
      through conventional washing or rubbing with an alcohol solution. There were 621
      opportunities for hand disinfection during P1 and 905 opportunities during P2.
      General compliance during P1 was 42.4%, and reached 60.9% during P2 (p < 0.001).
      This improvement was observed among nurses (45.3% versus 66.9%, p < 0.001),
      senior physicians (37. 2% versus 55.5%, p < 0.001), and residents (46.9% versus
      59.1%, p = 0.03). Acceptability and tolerance were evaluated through the answers
      to an anonymous questionnaire distributed to all 53 health care workers in the
      MICU. Rubbing with alcohol solution was an easy procedure (100% of responses) and
      induced mild side effects in less than 10% of respondents. In a complementary
      study conducted 3 mo after the first one, compliance remained better than during
      P1 (51. 3% versus 42.4%, p = 0.007). These findings suggest that rubbing with
      alcohol solution increases compliance with hand disinfection, and that it could
      be proposed as an alternative to conventional handwashing in the MICU.

PMID- 10903263
TI  - Treatment of nosocomial pneumonia and tracheobronchitis caused by multidrug
      resistant Pseudomonas aeruginosa with aerosolized colistin.
AB  - Gram-negative bacilli including multidrug-resistant (MDR) Pseudomonas aeruginosa
      are responsible for a significant proportion of episodes of nosocomial pneumonia.
      Since the development of new antibiotics with activity against gram-negative
      organisms has not kept pace with the increase in prevalence of MDR pathogens,
      there has been renewed interest in antimicrobial agents that had previously been
      used but had been abandoned because of toxic side effects. This report describes
      three patients with nosocomial pneumonia or tracheobronchitis due to
      multiresistant strains of P. aeruginosa for whom aerosolized colistin proved
      beneficial as supplemental therapy. Aerosolized colistin merits further
      consideration as a therapeutic intervention for patients with pulmonary
      infections due to MDR P. aeruginosa.

PMID- 10903264
TI  - Montelukast added to inhaled beclomethasone in treatment of asthma.

PMID- 10903265
TI  - Incidence and mortality after acute respiratory failure and acute respiratory
      distress syndrome in Sweden, Denmark, and Iceland.

PMID- 10903266
TI  - Ribavarin in ventilated respiratory syncytial virus bronchiolitis: a randomized,
      placebo-controlled trial.

PMID- 10903267
TI  - Editor's pick

PMID- 10903268
TI  - This month in wjm

PMID- 10903270
TI  - Exercise counseling in health promotion

PMID- 10903269
TI  - Can complementary medicine be evidence-based?

PMID- 10903271
TI  - Is equity a scientific issue?

PMID- 10903272
TI  - Guru promotes global health.

PMID- 10903273
TI  - Study explores internet as a tool for care of diabetic patients.

PMID- 10903274
TI  - Global news roundup

PMID- 10903275
TI  - Pro-sports medicine from the inside.

PMID- 10903276
TI  - A book that disturbed me

PMID- 10903277
TI  - Pregnancy saves lives.

PMID- 10903278
TI  - Author's response

PMID- 10903279
TI  - Analgesia in patients with acute abdomen.

PMID- 10903280
TI  - Fighting never pays.

PMID- 10903282
TI  - Unregulated potions still cause mercury poisoning

PMID- 10903281
TI  - Mercury poisoning associated with a Mexican beauty cream.
AB  - OBJECTIVES: To describe demographic characteristics, patterns of use, and
      symptoms associated with mercury poisoning among persons who used a Mexican
      beauty cream containing mercurous chloride and to estimate the prevalence of
      cream use in Texas near the Mexico border. DESIGN: Case series and cross
      sectional survey. SETTING: Border communities of Arizona, California, New Mexico,
      and Texas. PARTICIPANTS: Persons who used the cream and contacted a health
      department in response to announcements about the cream and households that
      participated in the Survey of Health and Environmental Conditions in Texas Border
      Counties and Colonias, 1997. MAIN OUTCOME MEASURES: Urine mercury concentrations,
      self-reported symptoms, and prevalence of cream use among households. RESULTS: Of
      330 cream users who contacted their health department, 96% were women, and 95%
      were Hispanic. The mean urine mercury concentration was 146.7 microg/L (reference
      range : 0-20 microg/L). In 5% of 2,194 randomly selected Texas households near
      the Mexico border, at least 1 person had used "Crema de Belleza-Manning"
      (Laboratorios Vida Natural, S.A., Tampico, Tamaulipas, Mexico) in the previous
      year. CONCLUSIONS: Most cream users had increased urine mercury concentrations.
      Cream use was common in Texas near the Mexico border. Physicians should consider
      toxicity in patients with neurologic symptoms of unclear cause and use public
      health departments when investigating unusual illnesses.

PMID- 10903284
TI  - Pica may be harmful to the fetus and mother

PMID- 10903285
TI  - Faith, hope, and charity: an in-depth interview study of cancer patients'
      information needs and information-seeking behavior
AB  - OBJECTIVE: To explore why cancer patients do not want or seek information about
      their condition beyond that volunteered by their physicians at times during their
      illness. DESIGN: Qualitative study based on in-depth interviews. SETTING:
      Outpatient oncology clinics at a London cancer center. PARTICIPANTS: 17 patients
      with cancer diagnosed in previous 6 months. Main outcome measures Analysis of
      patients' narratives to identify key themes and categories. RESULTS: While all
      patients wanted basic information on diagnosis and treatment, not all wanted
      further information at all stages of their illness. Three overarching attitudes
      to their management of cancer limited patients' desire for and subsequent efforts
      to obtain further information : faith, hope, and charity. Faith in their doctor's
      medical expertise precluded the need for patients to seek further information
      themselves. Hope was essential for patients to carry on with life as normal and
      could be maintained through silence and avoiding information, especially too
      detailed or "unsafe" information. Charity to fellow patients, especially those
      seen as more needy than themselves, was expressed in the recognition that scarce
      resources-including information and explanations-had to be shared and meant that
      limited information was accepted as inevitable. CONCLUSIONS: Cancer patients'
      attitudes to cancer and their strategies for coping with their illness can
      constrain their wish for information and their efforts to obtain it. In
      developing recommendations, the government's cancer information strategy should
      attend to variations in patients' desires for information and the reasons for
      them.

PMID- 10903283
TI  - Pica during pregnancy in low-income women born in Mexico.
AB  - OBJECTIVE: To describe pica behavior (ingestion of nonfood items) in pregnant low
      income Mexican-born women in Mexico and the United States. DESIGN: A convenience
      sample of informants was interviewed with a questionnaire containing open-ended
      and closed-ended questions. SETTING: A low-income community on the outskirts of
      Ensenada, Mexico, and clinics serving low-income people in southern California
      (Santa Ana, Bakersfield, and Los Angeles). PARTICIPANTS: Of a total of 225
      Mexican-born women, 75 (33%) were interviewed in Ensenada, and 150 (67%) were
      interviewed in southern California. RESULTS: The prevalence of pica during
      pregnancy was 44% (n = 33) in the Ensenada group and 31% (n = 46) in the southern
      California group. Those who reported pica behavior more commonly had a relative
      who also practiced pica. CONCLUSION: The high reported rate of pica in this
      sample indicates that pregnant Mexican-born women should be screened for pica and
      educated about the potentially serious effects on the fetus and mother.

PMID- 10903287
TI  - Personal narratives of well-being

PMID- 10903286
TI  - What cancer patients want to know: national strategies and individual needs

PMID- 10903288
TI  - A systematic review of treatment of settling problems and night waking in young
      children
AB  - OBJECTIVE: To assess the efficacy of treatment of settling problems and night
      waking in young children. DESIGN: A systematic review of randomized controlled
      trials of interventions. SETTING: Electronic bibliographic databases and
      references on identified papers, hand searches, and personal contact with
      specialists. SUBJECTS: Children aged 5 years or younger who had established
      settling problems or night waking. INTERVENTIONS: Interventions had to be
      described and a placebo, waiting list, or another intervention needed to have
      been used as a comparison. Interventions comprised drug trials or nondrug trials.
      Main outcome measures Number of wakes at night, time to settle, or number of
      nights in which these problems occurred. RESULTS: Drugs seemed to be effective in
      treating night waking in the short term, but long-term efficacy was questionable.
      In contrast, specific behavioral interventions showed both short-term efficacy
      and possible longer term effects for dealing with settling problems and night
      walking. CONCLUSIONS: Given the prevalence and persistence of childhood sleep
      problems and the effects they can have no children and families, treatments that
      offer long-lasting benefits are more appealing, and these are likely to be
      behavioral interventions.

PMID- 10903289
TI  - Challenges in managing sleep problems in young children

PMID- 10903290
TI  - What are the experiences of women with breast cancer as they decide whether to
      use complementary/alternative medicine?

PMID- 10903291
TI  - Can a school - based intervention to reduce television use decrease adiposity in
      children in grades 3 and 4 ?

PMID- 10903292
TI  - What is the meaning of sexual violence in the lives of women who have been
      sexually assaulted by men they knew well?

PMID- 10903293
TI  - Which antibiotics lead to higher clinical cure rates in adults with acute
      maxillary sinusitis?

PMID- 10903295
TI  - Drug resistant bacteria cause fresh concern

PMID- 10903296
TI  - Moderate drinking protects against diabetes

PMID- 10903294
TI  - Plant sterol and stanol margarines and health.

PMID- 10903298
TI  - Any Questions? any answers?

PMID- 10903297
TI  - Digestive system disorders: gastroesophageal reflux disease.
AB  - This article comes from Clinical Evidence (1999; 1 : 145-153), a new resource for
      clinicians produced jointly by the BMJ Publishing Group and the American College
      of Physicians-American Society of Internal Medicine. Clinical Evidence is an
      extensively peer-reviewed publication that summarizes the best available evidence
      on the effects of common clinical interventions gleaned from thorough searches
      and appraisal of the world literature. It became available in the United States
      late last year. Please see advertisement for more information or, alternatively,
      visit the web site at www. evidence.org.

PMID- 10903300
TI  - Exploring the genome

PMID- 10903302
TI  - Can bleeding problems present initially during sports activity?

PMID- 10903301
TI  - Do high factor sunscreens offer protection from melanoma?

PMID- 10903299
TI  - The glitazones: proceed with caution.

PMID- 10903303
TI  - Chronic lower limb ischemia.

PMID- 10903304
TI  - The predicaments of "dangerous safety": living with juvenile diabetes in 20th
      century America.
AB  - Remedies are not useless because they fall short of their full scope. It is
      better to keep a man on the edge of a precipice, if you cannot pluck him away
      from it, than to let him fall over. And many diabetic patients are kept in this
      predicament of dangerous safety. Lectures on the Principles and Practice of
      Physic, 1836-1837 SirThomas Watson

PMID- 10903305
TI  - Iranian births.

PMID- 10903306
TI  - A breach of "etiquette"?

PMID- 10903307
TI  - Practice point

PMID- 10903308
TI  - Hunger and thirst

PMID- 10903309
TI  - Bacillus subtilis YqkI is a novel malic/Na+-lactate antiporter that enhances
      growth on malate at low protonmotive force.
AB  - Bacillus subtilis yheL encodes a Na(+)/H(+) antiporter, whereas its paralogue,
      yqkI, encodes a novel antiporter that achieves a simultaneous Na(+)/H(+) and
      malolactate antiport. B. subtilis yufR, a control in some experiments, encodes a
      Na(+)/malate symporter. YqkI complemented a malate transport mutant of
      Escherichia coli if Na(+) and lactate were present. YheL conferred Na(+) uptake
      capacity on everted membrane vesicles from an antiporter-deficient E. coli mutant
      that was consistent with a secondary Na(+)/H(+) antiport, but YqkI-dependent
      Na(+) uptake depended on intravesicular malate and extravesicular lactate. YqkI
      dependent lactate uptake depended on intravesicular malate and extravesicular
      Na(+). YqkI mediated an electroneutral exchange, which is proposed to be a malic(
      2)-2H(+) (or fully protonated malate)/Na(+)-lactate(-1) antiport. Because the
      composite YqkI-mediated exchanges could be driven by gradients of the malate
      lactate pair, this transporter could play a role in growth of B. subtilis on
      malate at low protonmotive force. A mutant with a disruption of yqkI exhibited an
      abrupt arrest in the mid-logarithmic phase of growth on malate when low
      concentrations of protonophore were present. Thus growth of B. subtilis to high
      density on a putatively nonfermentative dicarboxylic acid substrate depends on a
      malolactate exchange at suboptimal protonmotive force.

PMID- 10903310
TI  - EPR and Mossbauer studies of benzoyl-CoA reductase.
AB  - Benzoyl-CoA reductase catalyzes the two-electron transfer from a reduced
      ferredoxin to the aromatic ring of benzoyl-CoA; this reaction is coupled to
      stoichiometrical ATP hydrolysis. A very low reduction potential (less than -1 V)
      is required for the first electron transfer to the aromatic ring. In this work
      the nature of the redox centers of purified benzoyl-CoA reductase from Thauera
      aromatica was studied by EPR and Mossbauer spectroscopy. The results obtained
      indicated the presence of three [4Fe-4S] clusters. Redox titration studies
      revealed that the reduction potentials of all three clusters were below -500 mV.
      The previously reported S = 7/2 state of the enzyme during benzoyl-CoA
      independent ATPase activity (Boll, M., Albracht, S. J. P., and Fuchs, G. (1997)
      Eur. J. Biochem. 244, 840-851) was confirmed by Mossbauer spectroscopy.
      Inactivation by oxygen was associated with the irreversible conversion of part of
      the [4Fe-4S] clusters to [3Fe-4S] clusters. Acetylene stimulated the benzoyl-CoA
      independent ATPase activity and induced novel EPR signals with g(av) >2. The
      presence of simple cubane clusters in benzoyl-CoA reductase as the sole redox
      active metal centers demonstrates novel aspects of [4Fe-4S] clusters since they
      adopt the role of elemental sodium or lithium which are used as electron donors
      in the analogous chemical Birch reduction of aromatic rings.

PMID- 10903311
TI  - Cell confluence-dependent remodeling of endothelial membranes mediated by
      cholesterol.
AB  - The plasma membranes of endothelial cells reaching confluence undergo profound
      structural and functional modifications, including the formation of adherens
      junctions, crucial for the regulation of vascular permeability and angiogenesis.
      Adherens junction formation is accompanied by the tyrosine dephosphorylation of
      adherens junctions proteins, which has been correlated with the strength and
      stability of adherens junctions. Here we show that cholesterol is a critical
      determinant of plasma membrane remodeling in cultures of growing cow pulmonary
      aortic endothelial cells. Membrane cholesterol increased dramatically at an early
      stage in the formation of confluent cow pulmonary aortic endothelial cell
      monolayers, prior to formation of intercellular junctions. This increase was
      accompanied by the redistribution of caveolin from a high density to a low
      density membrane compartment, previously shown to require cholesterol, and
      increased binding of the annexin II-p11 complex to membranes, consistent with
      other studies indicating cholesterol-dependent binding of annexin II to
      membranes. Furthermore, partial depletion of cholesterol from confluent cells
      with methyl-beta-cyclodextrin both induced tyrosine phosphorylation of multiple
      membrane proteins, including adherens junctions proteins, and disrupted adherens
      junctions. Both effects were dramatically reduced by prior complexing of methyl
      beta-cyclodextrin with cholesterol. Our results reveal a novel physiological role
      for cholesterol regulating the formation of adherens junctions and other plasma
      membrane remodeling events as endothelial cells reach confluence.

PMID- 10903312
TI  - Reconstituting the barrier properties of a water-tight epithelial membrane by
      design of leaflet-specific liposomes.
AB  - To define aspects of lipid composition and bilayer asymmetry critical to barrier
      function, we examined the permeabilities of liposomes that model individual
      leaflets of the apical membrane of a barrier epithelium, Madin-Darby canine
      kidney type 1 cells. Using published lipid compositions we prepared exofacial
      liposomes containing phosphatidylcholine, sphingomyelin, glycosphingolipids, and
      cholesterol; and cytoplasmic liposomes containing phosphatidylethanolamine,
      phosphatidylserine, and cholesterol. The osmotic permeability of cytoplasmic
      liposomes to water (P(f)), solutes, and NH(3) was 18-90-fold higher than for the
      exofacial liposomes (P(f(ex)) = 2.4 +/- 0.4 x 10(-4) cm/s, P(f(cy)) = 4.4 +/- 0.3
      x 10(-3) cm/s; P(glycerol(ex)) = 2.5 +/- 0.3 x 10(-8) cm/s, P(glycerol(cy)) = 2.2
      +/- 0.02 x 10(-6) cm/s; P(NH3(ex)) = 0. 13 +/- 0.4 x 10(-4) cm/s, P(NH3(cy)) =
      7.9 +/- 1.0 x 10(-3) cm/s). By contrast, the apparent proton permeability of
      exofacial liposomes was 4-fold higher than cytoplasmic liposomes (P(H+(ex)) = 1.1
      +/- 0. 1 x 10(-2) cm/s, P(H+(cy)) = 2.7 +/- 0.6 x 10(-3) cm/s). By adding single
      leaflet permeabilities, we calculated a theoretical P(f) for a Madin-Darby canine
      kidney apical membrane of 4.6 x 10(-4) cm/s, which compares favorably with
      experimentally determined values. In exofacial liposomes lacking
      glycosphingolipids or sphingomyelin, permeabilities were 2-7-fold higher,
      indicating that both species play a role in barrier function. Removal of
      cholesterol resulted in 40-280-fold increases in permeability. We conclude: 1)
      that we have reconstituted the biophysical properties of a barrier membrane, 2)
      that the barrier resides in the exofacial leaflet, 3) that both sphingomyelin and
      glycosphingolipids play a role in reducing membrane permeability but that there
      is an absolute requirement for cholesterol to mediate this effect, 4) that these
      results further validate the hypothesis that each leaflet offers an independent
      resistance to permeation, and 5) that proton permeation was enhanced by
      sphingolipid/cholesterol interactions.

PMID- 10903313
TI  - Targeting of aminopeptidase I to the yeast vacuole is mediated by Ssa1p, a
      cytosolic member of the 70-kDa stress protein family.
AB  - The two cytosolic members of the highly conserved 70-kDa stress protein family,
      Ssa1p and Ssa2p, were specifically retained by the prepro-NH(2) extension of the
      vacuolar aminopeptidase I precursor (pAPI) conjugated to agarose (Sulfolink). A
      temperature-sensitive mutant strain a1(ts)a234 (ssa1(ts) ssa2 ssa3 ssa4), when
      incubated at the restrictive temperature, was able to assemble the API precursor
      into dodecamers, but failed to pack pAPI into vesicles and to convert it into
      mature API (mAPI), a process that occurs in the vacuole. Altogether these results
      indicate that Ssa1p mediates the targeting of pAPI to the vacuole.

PMID- 10903314
TI  - Imaging DNA loops induced by restriction endonuclease EcoRII. A single amino acid
      substitution uncouples target recognition from cooperative DNA interaction and
      cleavage.
AB  - EcoRII is a type IIE restriction endonuclease characterized by a highly
      cooperative reaction mechanism that depends on simultaneous binding of the
      dimeric enzyme molecule to two copies of its DNA recognition site. Transmission
      electron microscopy provided direct evidence that EcoRII mediates loop formation
      of linear DNA containing two EcoRII recognition sites. Specific DNA binding of
      EcoRII revealed a symmetrical DNase I footprint occupying 16-18 bases. Single
      amino acid replacement of Val(258) by Asn yielded a mutant enzyme that was
      unaffected in substrate affinity and DNase I footprinting properties, but
      exhibited a profound decrease in cooperative DNA binding and cleavage activity.
      Because the electrophoretic mobility of the mutant enzyme-DNA complexes was
      significantly higher than that of the wild-type, we investigated if mutant V258N
      binds as a monomer to the substrate DNA. Analysis of the molecular mass of mutant
      V258N showed a high percentage of protein monomers in solution. The dissociation
      constant of mutant V258N confirmed a 350-fold decrease of the enzyme dimerization
      capability. We conclude that Val(258) is located in a region of EcoRII involved
      in homodimerization. This is the first report of a specific amino acid
      replacement in a restriction endonuclease leading to the loss of dimerization and
      DNA cleavage while retaining specific DNA binding.

PMID- 10903315
TI  - Functional and structural characterization of synthetic HIV-1 Vpr that transduces
      cells, localizes to the nucleus, and induces G2 cell cycle arrest.
AB  - Human immunodeficiency virus (HIV) Vpr contributes to nuclear import of the viral
      pre-integration complex and induces G(2) cell cycle arrest. We describe the
      production of synthetic Vpr that permitted the first studies on the structure and
      folding of the full-length protein. Vpr is unstructured at neutral pH, whereas
      under acidic conditions or upon addition of trifluorethanol it adopts alpha
      helical structures. Vpr forms dimers in aqueous trifluorethanol, whereas
      oligomers exist in pure water. (1)H NMR spectroscopy allows the signal assignment
      of N- and C-terminal amino acid residues; however, the central section of the
      molecule is obscured by self-association. These findings suggest that the in vivo
      folding of Vpr may require structure-stabilizing interacting factors such as
      previously described interacting cellular and viral proteins or nucleic acids. In
      biological studies we found that Vpr is efficiently taken up from the
      extracellular medium by cells in a process that occurs independent of other HIV-1
      proteins and appears to be independent of cellular receptors. Following cellular
      uptake, Vpr is efficiently imported into the nucleus of transduced cells.
      Extracellular addition of Vpr induces G(2) cell cycle arrest in dividing cells.
      Together, these findings raise the possibility that circulating forms of Vpr
      observed in HIV-infected patients may exert biological effects on a broad range
      of host target cells.

PMID- 10903316
TI  - Inhibition of neuronal apoptosis by docosahexaenoic acid (22:6n-3). Role of
      phosphatidylserine in antiapoptotic effect.
AB  - Enrichment of Neuro 2A cells with docosahexaenoic acid (22:6n-3) decreased
      apoptotic cell death induced by serum starvation as evidenced by the reduced DNA
      fragmentation and caspase-3 activity. The protective effect of 22:6n-3 became
      evident only after at least 24 h of enrichment before serum starvation and was
      potentiated as a function of the enrichment period. During enrichment 22:6n-3
      incorporated into phosphatidylserine (PS) steadily, resulting in a significant
      increase in the total PS content. Similar treatment with oleic acid (18:1n-9)
      neither altered PS content nor resulted in protective effect. Hindering PS
      accumulation by enriching cells in a serine-free medium diminished the protective
      effect of 22:6n-3. Membrane translocation of Raf-1 was significantly enhanced by
      22:6n-3 enrichment in Neuro 2A cells. Consistently, in vitro biomolecular
      interaction between PS/phosphatidylethanolamine /phosphatidylcholine liposomes,
      and Raf-1 increased in a PS concentration-dependent manner. Collectively,
      enrichment of neuronal cells with 22:6n-3 increases the PS content and Raf-1
      translocation, down-regulates caspase-3 activity, and prevents apoptotic cell
      death. Both the antiapoptotic effect of 22:6n-3 and Raf-1 translocation are
      sensitive to 22:6n-3 enrichment-induced PS accumulation, strongly suggesting that
      the protective effect of 22:6n-3 may be mediated at least in part through the
      promoted accumulation of PS in neuronal membranes.

PMID- 10903317
TI  - Biochemical and molecular analyses of the Streptococcus pneumoniae acyl carrier
      protein synthase, an enzyme essential for fatty acid biosynthesis.
AB  - Acyl carrier protein synthase (AcpS) is an essential enzyme in the biosynthesis
      of fatty acids in all bacteria. AcpS catalyzes the transfer of 4'
      phosphopantetheine from coenzyme A (CoA) to apo-ACP, thus converting apo-ACP to
      holo-ACP that serves as an acyl carrier for the biosynthesis of fatty acids and
      lipids. To further understand the physiological role of AcpS, we identified,
      cloned, and expressed the acpS and acpP genes of Streptococcus pneumoniae and
      purified both products to homogeneity. Both acpS and acpP form operons with the
      genes whose functions are required for other cellular metabolism. The acpS gene
      complements an Escherichia coli mutant defective in the production of AcpS and
      appears to be essential for the growth of S. pneumoniae. Gel filtration and cross
      linking analyses establish that purified AcpS exists as a homotrimer. AcpS
      activity was significantly stimulated by apo-ACP at concentrations over 10 microm
      and slightly inhibited at concentrations of 5-10 microm. Double reciprocal
      analysis of initial velocities of AcpS at various concentrations of CoA or apo
      ACP indicated a random or compulsory ordered bi bi type of reaction mechanism.
      Further analysis of the inhibition kinetics of the product (3',5'-ADP) suggested
      that it is competitive with respect to CoA but mixed (competitive and
      noncompetitive) with respect to apo-ACP. Finally, apo-ACP bound tightly to AcpS
      in the absence of CoA, but CoA failed to do so in the absence of apo-ACP.
      Together, these results suggest that AcpS may be allosterically regulated by apo
      ACP and probably proceeds by an ordered reaction mechanism with the first
      formation of the AcpS-apo-ACP complex and the subsequent transfer of 4'
      phosphopantetheine to the apo-ACP of the complex.

PMID- 10903318
TI  - Both RadA and RadB are involved in homologous recombination in Pyrococcus
      furiosus.
AB  - RecA and Rad51 proteins are essential for homologous recombination in Bacteria
      and Eukarya, respectively. Homologous proteins, called RadA, have been described
      for Archaea. Here we present the characterization of two RecA/Rad51 family
      proteins, RadA and RadB, from Pyrococcus furiosus. The radA and radB genes were
      not induced by DNA damage resulting from exposure of the cells to gamma and UV
      irradiation and heat shock, suggesting that they might be constitutively
      expressed in this hyperthermophile. RadA had DNA-dependent ATPase, D-loop
      formation, and strand exchange activities. In contrast, RadB had a very weak
      ATPase activity that is not stimulated by DNA. This protein had a strong binding
      affinity for DNA, but little strand exchange activity could be detected. A direct
      interaction between RadA and RadB was detected by an immunoprecipitation assay.
      Moreover, RadB, but not RadA, coprecipitated with Hjc, a Holliday junction
      resolvase found in P. furiosus, in the absence of ATP. This interaction was
      suppressed in the presence of ATP. The Holliday junction cleavage activity of Hjc
      was inhibited by RadB in the absence, but not in the presence, of ATP. These
      results suggest that RadB has important roles in homologous recombination in
      Archaea and may regulate the cleavage reactions of the branch-structured DNA.

PMID- 10903319
TI  - Purification and characterization of UDP-GlcNAc: GlcNAcbeta 1-6(GlcNAcbeta 1
      2)Manalpha 1-R [GlcNAc to Man]-beta 1, 4-N-acetylglucosaminyltransferase VI from
      hen oviduct.
AB  - A new beta1,4-N-acetylglucosaminyltransferase (GnT) responsible for the formation
      of branched N-linked complex-type sugar chains has been purified 64,000-fold in
      16% yield from a homogenate of hen oviduct by column chromatography procedures
      using Q-Sepharose FF, Ni(2+)-chelating Sepharose FF, and UDP-hexanolamine
      agarose. This enzyme catalyzes the transfer of GlcNAc from UDP-GlcNAc to
      tetraantennary oligosaccharide and produces pentaantennary oligosaccharide with
      the beta1-4-linked GlcNAc residue on the Manalpha1-6 arm. It requires a divalent
      cation such as Mn(2+) and has an apparent molecular weight of 72,000 under
      nonreducing conditions. The enzyme does not act on biantennary oligosaccharide
      (GnT I and II product), and beta1,6-N-acetylglucosaminylation of the Manalpha1-6
      arm (GnT V product) is essential for its activity. This clearly distinguishes it
      from GnT IV, which is known to generate a beta1-4-linked GlcNAc residue only on
      the Manalpha1-3 arm. Based on these findings, we conclude that this enzyme is UDP
      GlcNAc:GlcNAcbeta1-6(GlcNAcbeta1-2)Manalpha1-R [GlcNAc to Man]-beta1,4-N
      acetylglucosaminyltransferase VI. This is the only known enzyme that has not been
      previously purified among GnTs responsible for antenna formation on the cores of
      N-linked complex-type sugar chains.

PMID- 10903320
TI  - A method for determining the in vivo topology of yeast polytopic membrane
      proteins demonstrates that Gap1p fully integrates into the membrane independently
      of Shr3p.
AB  - The general amino acid permease (Gap1p) of Saccharomyces cerevisiae is an
      integral membrane protein that contains 12 hydrophobic regions predicted to be
      membrane-spanning segments. A topological reporter construct, encoding an
      internal 53-amino acid peptide of invertase (Suc2p) containing three Asp-X
      Ser/Thr glycosylation sites, was inserted in-frame into the hydrophilic NH(2)-
      and COOH-terminal domains and each of the 11 hydrophilic loops that separate the
      12 hydrophobic segments of Gap1p. The resulting 13 gene sandwich fusion proteins
      were expressed in a gap1Delta null mutant strain; 9 of these retain amino acid
      transport activity and are folded and correctly targeted to the plasma membrane.
      The glycosylation state of each of the fusion proteins was monitored; the results
      indicate that all 12 hydrophobic segments of Gap1p span the membrane, and the
      NH(2) and COOH termini are cytoplasmically oriented. These results were
      independently tested by isolating sealed right-side-out microsomes from sec12-1
      strains expressing six different Gap1p constructs containing functional factor Xa
      protease cleavage sites. The pattern of factor Xa protease cleavage was found to
      be consistent with the presence of 12 membrane-spanning domains. Gap1p exhibited
      the same membrane topology in strains lacking Shr3p; therefore, Gap1p fully
      integrates into the ER membrane independently of this permease-specific packaging
      chaperone.

PMID- 10903321
TI  - Tetrameric assembly and conservation in the ATP-binding domain of rat branched
      chain alpha-ketoacid dehydrogenase kinase.
AB  - We showed previously that the rat branched-chain alpha-ketoacid dehydrogenase
      (BCKD) kinase is capable of autophosphorylation. However, despite its sequence
      similarity to bacterial histidine protein kinases, BCKD kinase does not function
      as a histidine protein kinase. In the present study, we report that the rat BCKD
      kinase exists as a homotetramer of M(r) = 185,000, based on results of gel
      filtration and dynamic light scattering. This is in contrast to the related
      mammalian pyruvate dehydrogenase kinase isozymes that occur as homodimers. The
      tetrameric assembly of BCKD kinase was confirmed by the presence of four 5'
      adenylyl-imidodiphosphate-binding sites (K(D) = 4.1 x 10(-6)m) per molecule of
      the kinase. Incubation of the BCKD kinase with increasing concentrations of urea
      resulted in dissociation of the tetramer to dimers and eventually to monomers as
      separated on a sucrose density gradient. Both tetramers and dimers, but not the
      monomer, maintained the conformation capable of binding ATP and undergoing
      autophosphorylation. BCKD kinase depends on a fully lipoylated transacylase for
      maximal activity, but the interaction between the kinase and the transacylase is
      impeded in the presence of high salt concentrations. Alterations of conserved
      residues in the ATP-binding domain led to a marked reduction or complete loss in
      the catalytic efficiency of the BCKD kinase. The results indicate that BCKD
      kinase, similar to pyruvate dehydrogenase kinase isozymes, belongs to the
      superfamily of ATPase/kinase.

PMID- 10903322
TI  - Trans complementation of variant Cre proteins for defects in cleavage and
      synapsis.
AB  - The Cre recombinase is a member of the integrase family of conservative site
      specific recombinases. These proteins share five conserved catalytic residues,
      one of which is a tyrosine that acts as the nucleophile to attack the scissile
      phosphodiester bond in the DNA target. Recombination by the Cre recombinase takes
      place in a supramolecular structure called a synapse that consists of four
      molecules of Cre bound to two DNA target sequences called lox sites. The synapse
      is held together by an intricate network of protein-protein interactions. They
      bend the two sites into square planar structure that resembles a Holliday
      intermediate. We have studied three mutant Cre proteins that appear to have
      defects in synapsis (Cre A36V, Cre T41F, and Cre G314R). We found that they were
      unable to carry out strand cleavage but that cleavage occurred if they were mixed
      with a cleavage-defective Cre protein that lacks the catalytic nucleophilic
      tyrosine residue. The three variant proteins could also be complemented for the
      formation of a novel structure ("complexV"), which may be a cleaved synaptic
      intermediate. We suggest that these three mutant proteins have a defect in DNA
      bending and discuss the relationship between bending, synapsis, and cleavage.

PMID- 10903323
TI  - Tumor necrosis factor-alpha inhibits transforming growth factor-beta /Smad
      signaling in human dermal fibroblasts via AP-1 activation.
AB  - Understanding the molecular mechanisms underlying the antagonistic activities of
      tumor necrosis factor-alpha (TNF-alpha) against transforming growth factor-beta
      (TGF-beta) is of utmost importance given the physiopathological implications of
      these cytokines. In this report, we demonstrate that TNF-alpha prevents TGF-beta
      induced Smad-specific gene transactivation without inducing detectable levels of
      inhibitory Smad7 in human dermal fibroblasts. On the other hand, c-Jun and JunB,
      both induced by TNF-alpha, block Smad3-mediated transcription. Expression of
      antisense c-Jun mRNA prevents TNF-alpha inhibition of TGF-beta/Smad signaling
      whereas that of dominant-negative Ikappa-B kinase-alpha or antisense Smad7 does
      not. We provide evidence for off-DNA interactions between Smad3 and both c-Jun
      and JunB accompanied with reduced Smad3-DNA interactions. Finally, we show that
      overexpression of the transcriptional co-activator p300 prevents TNF-alpha/AP-1
      inhibition of TGF-beta/Smad signaling. These data suggest that TNF-alpha
      interferes with Smad signaling through the induction of AP-1 components, the
      latter forming off-DNA complexes with Smad3 and preventing its binding to
      specific cis-element(s). In addition, Jun members compete with Smad3 for the
      common transcription co-activator p300. These two mechanisms are likely to act in
      concert to decrease Smad-specific transcription.

PMID- 10903324
TI  - CGRP-RCP, a novel protein required for signal transduction at calcitonin gene
      related peptide and adrenomedullin receptors.
AB  - It is becoming clear that receptors that initiate signal transduction by
      interacting with G-proteins do not function as monomers, but often require
      accessory proteins for function. Some of these accessory proteins are chaperones,
      required for correct transport of the receptor to the cell surface, but the
      function of many accessory proteins remains unknown. We determined the role of an
      accessory protein for the receptor for calcitonin gene-related peptide (CGRP), a
      potent vasodilator neuropeptide. We have previously shown that this accessory
      protein, the CGRP-receptor component protein (RCP), is expressed in CGRP
      responsive tissues and that RCP protein expression correlates with the biological
      efficacy of CGRP in vivo. However, the function of RCP has remained elusive. In
      this study stable cell lines were made that express antisense RCP RNA, and CGRP-
      and adrenomedullin-mediated signal transduction were greatly reduced. However,
      the loss of RCP did not effect CGRP binding or receptor density, indicating that
      RCP did not behave as a chaperone but was instead coupling the CGRP receptor to
      downstream effectors. A candidate CGRP receptor named calcitonin receptor-like
      receptor (CRLR) has been identified, and in this study RCP co-immunoprecipitated
      with CRLR indicating that these two proteins interact directly. Since CGRP and
      adrenomedullin can both signal through CRLR, which has been previously shown to
      require a chaperone protein for function, we now propose that a functional CGRP
      or adrenomedullin receptor consists of at least three proteins: the receptor
      (CRLR), the chaperone protein (RAMP), and RCP that couples the receptor to the
      cellular signal transduction pathway.

PMID- 10903325
TI  - Oxygen requirement for the biosynthesis of the S-2-hydroxymyristate moiety in
      Salmonella typhimurium lipid A. Function of LpxO, A new Fe2+/alpha-ketoglutarate
      dependent dioxygenase homologue.
AB  - Lipid A molecules of certain Gram-negative bacteria, including Salmonella
      typhimurium and Pseudomonas aeruginosa, may contain secondary S-2-hydroxyacyl
      chains. S. typhimurium has recently been shown to synthesize its S-2
      hydroxymyristate-modified lipid A in a PhoP/PhoQ-dependent manner, suggesting a
      possible role for the 2-OH group in pathogenesis. We postulated that 2
      hydroxylation might be catalyzed by a novel dioxygenase. Lipid A was extracted
      from a PhoP-constitutive mutant of S. typhimurium grown in the presence or
      absence of O(2). Under anaerobic conditions, no 2-hydroxymyristate-containing
      lipid A was formed. Matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry of lipid A from cells grown in the presence of (18)O(2)
      confirmed the direct incorporation of molecular oxygen into 2-hydroxyacyl
      modified lipid A. Using several well characterized dioxygenase protein sequences
      as probes, tBLASTn searches revealed unassigned open reading frame(s) with
      similarity to mammalian aspartyl/asparaginyl beta-hydroxylases in bacteria known
      to make 2-hydroxyacylated lipid A molecules. The S. typhimurium
      aspartyl/asparaginyl beta-hydroxylase homologue (designated lpxO) was cloned into
      pBluescriptSK and expressed in Escherichia coli K-12, which does not contain
      lpxO. Analysis of the resulting construct revealed that lpxO expression is
      sufficient to induce O(2)-dependent formation of 2-hydroxymyristate-modified
      lipid A in E. coli. LpxO very likely is a novel Fe(2+)/alpha-ketoglutarate
      dependent dioxygenase that catalyzes the hydroxylation of lipid A (or of a key
      precursor). The S. typhimurium lpxO gene encodes a polypeptide of 302 amino acids
      with predicted membrane-anchoring sequences at both ends. We hypothesize that 2
      hydroxymyristate chains released from lipopolysaccharide inside infected
      macrophages might be converted to 2-hydroxymyristoyl coenzyme A, a well
      characterized, potent inhibitor of protein N-myristoyl transferase.

PMID- 10903326
TI  - Virus-mediated transduction of apolipoprotein E (ApoE)-sendai develops
      lipoprotein glomerulopathy in ApoE-deficient mice.
AB  - Lipoprotein glomerulopathy (LPG) is a unique renal disease characterized by
      thrombus-like substances in markedly dilated glomerular capillaries,
      dysbetalipoproteinemia, and elevated plasma concentrations of apoE. Recent
      studies identified several apoE mutations in patients with LPG, including
      apoE2(R145P) Sendai (apoE-Sendai). Virus-mediated transduction of apoE-Sendai in
      apoE-deficient hypercholesterolemic mice resulted in insufficient correction of
      hypercholesterolemia and a marked and temporal induction of plasma triglyceride
      levels. In vitro binding studies showed that apoE-Sendai has a reduced affinity
      for the low density lipoprotein receptor, suggesting that dysbetalipoproteinemia
      in LPG is caused by the apoE mutation. Furthermore, histological examination
      revealed marked intraglomerular depositions of apoE-containing lipoproteins in
      mice injected with apoE-Sendai virus. These LPG-like depositions were detected 6
      days after virus injection and were sustained for at least 60 days. Our results
      demonstrated that apoE-Sendai is an etiological cause of LPG.

PMID- 10903327
TI  - X-ray crystal structure of a small antagonist peptide bound to interleukin-1
      receptor type 1.
AB  - Interleukin (IL-1)alpha and IL-1beta are important mediators of inflammation. The
      binding of IL-1 to interleukin-1 receptor (IL-1R) type 1 is the initial step in
      IL-1 signal transduction and therefore is a tempting target for anti-inflammatory
      therapeutics. To advance our understanding of IL-1R1 binding interactions, we
      have determined the structure of the extracellular domains of IL-1R1 bound to a
      21-amino acid IL-1 antagonist peptide at 3.0-A resolution. The antagonist peptide
      binds to the domain 1/2 junction of the receptor, which is a conserved binding
      site for IL-1beta and IL-1 receptor antagonist (IL-1ra). This co-crystal
      structure also reveals that considerable flexibility is present in IL-1R1 because
      the carboxyl-terminal domain of the receptor is rotated almost 170 degrees
      relative to the first two domains of the receptor compared with the previously
      solved IL-1R1.ligand structures. The structure shows an unexpected binding mode
      for the peptide and may contribute to the design of smaller IL-1R antagonists.

PMID- 10903328
TI  - Series introduction: the molecular and physiological basis of insulin resistance:
      emerging implications for metabolic and cardiovascular diseases.

PMID- 10903329
TI  - Signaling pathways in insulin action: molecular targets of insulin resistance.

PMID- 10903330
TI  - Cellular mechanisms of insulin resistance.

PMID- 10903331
TI  - Novel treatments for osteoporosis.

PMID- 10903332
TI  - Gene therapy in the treatment of autoimmune diseases.

PMID- 10903333
TI  - Haploinsufficiency of the melanocortin-4 receptor: part of a thrifty genotype?

PMID- 10903334
TI  - 15-deoxy-delta(12,14)-PGJ(2) induces synoviocyte apoptosis and suppresses
      adjuvant-induced arthritis in rats.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily and have a dominant regulatory role in adipocyte and
      monocyte differentiation. PPAR-gamma agonists are also negative regulators of
      macrophage activation and have modulatory effects on tumorigenesis. In this study
      we demonstrate that synovial tissue localized expression of PPAR-gamma in
      patients with rheumatoid arthritis (RA). We detected markedly enhanced expression
      of PPAR-gamma in macrophages, as well as modestly enhanced expression in the
      synovial lining layer, fibroblasts, and endothelial cells. Activation of the PPAR
      gamma by 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and the synthetic
      PPAR-gamma ligand (troglitazone) induced RA synoviocyte apoptosis in vitro.
      Moreover, intraperitoneal administration of these PPAR-gamma ligands ameliorated
      adjuvant-induced arthritis with suppression of pannus formation and mononuclear
      cell infiltration in female Lewis rats. Anti-inflammatory effects of 15d-PGJ(2)
      were more potent than troglitazone. These findings suggest that PPAR-gamma may be
      an important immunoinflammatory mediator and its ligands, especially 15d-PGJ(2),
      may be useful in the treatment of RA.

PMID- 10903335
TI  - Systemically derived large intestinal CD4(+) Th2 cells play a central role in
      STAT6-mediated allergic diarrhea.
AB  - Systemically primed BALB/c mice developed severe diarrhea after repeated oral
      administration of ovalbumin (OVA). Histological analysis demonstrated that
      dramatic infiltration of eosinophils and mast cells occurred in the large
      intestine but not in the small intestine of mice with diarrhea. Interestingly,
      CD4(+) alphabeta T cells of the large intestine secreted IL-4 and IL-13 at high
      levels. Identically treated STAT6 gene-disrupted mice failed to develop OVA
      induced diarrhea. Further, treatment of BALB/c mice with monoclonal anti-IL-4
      antibody prevented the development of allergic diarrhea. An adoptive transfer
      study showed that systemically primed splenic CD4(+) T cells were preferentially
      recruited into the large intestine upon exposure to oral OVA. These results
      strongly suggest that systemically derived CD4(+) alphabeta T cells of the large
      intestine play a critical role in the onset of Th2-mediated intestinal allergic
      disorders via STAT6 signal transduction.

PMID- 10903336
TI  - Treatment of murine lupus with cDNA encoding IFN-gammaR/Fc.
AB  - IFN-gamma, a pleiotropic cytokine, is a key effector molecule in the pathogenesis
      of several autoimmune diseases, including lupus. Importantly, deletion of IFN
      gamma or IFN-gammaR in several lupus-predisposed mouse strains resulted in
      significant disease reduction, suggesting the potential for therapeutic
      intervention. We evaluated whether intramuscular injections of plasmids with cDNA
      encoding IFN-gammaR/Fc can retard lupus development and progression in MRL
      Fas(lpr) mice. Therapy significantly reduced serum levels of IFN-gamma, as well
      as disease manifestations (autoantibodies, lymphoid hyperplasia,
      glomerulonephritis, mortality), when treatment was initiated at the predisease
      stage, particularly when IFN-gammaR/Fc expression was enhanced by electroporation
      at the injection site. Remarkably, disease was arrested and even ameliorated when
      this treatment was initiated at an advanced stage. This therapy represents a rare
      example of disease reversal and makes application of this nonviral gene therapy
      in humans with lupus (and perhaps other autoimmune/inflammatory conditions)
      highly promising.

PMID- 10903338
TI  - Targeted expression of a dominant-negative EGF-R in the kidney reduces tubulo
      interstitial lesions after renal injury.
AB  - The role of EGF in the evolution of renal lesions after injury is still
      controversial. To determine whether the EGF expression is beneficial or
      detrimental, we generated transgenic mice expressing a COOH-terminal-truncated
      EGF-R under the control of the kidney-specific type 1 gamma-glutamyl
      transpeptidase promoter. As expected, the transgene was expressed exclusively at
      the basolateral membrane of proximal tubular cells. Under basal conditions,
      transgenic mice showed normal renal morphology and function. Infusion of EGF to
      transgenic animals revealed that the mutant receptor behaved in a dominant
      negative manner and prevented EGF-signaled EGF-R autophosphorylation. We next
      evaluated the impact of transgene expression on the development of renal lesions
      in two models of renal injury. After 75% reduction of renal mass, tubular
      dilations were less severe in transgenic mice than in wild-type animals. After
      prolonged renal ischemia, tubular atrophy and interstitial fibrosis were reduced
      in transgenic mice as compared with wild-type mice. The beneficial effect of the
      transgene included a reduction of tubular cell proliferation, interstitial
      collagen accumulation, and mononuclear cell infiltration. In conclusion,
      functional inactivation of the EGF-R in renal proximal tubular cells reduced
      tubulo-interstitial lesions after renal injury. These data suggest that blocking
      the EGF pathway may be a therapeutic strategy to reduce the progression of
      chronic renal failure.

PMID- 10903337
TI  - Cytotoxic mAb from rheumatic carditis recognizes heart valves and laminin.
AB  - Anti-streptococcal antibodies cross-reactive with N-acetyl-betaD-glucosamine
      (GlcNAc) and myosin are present in the sera of patients with rheumatic fever
      (RF). However, their role in tissue injury is not clear. In this study, we show
      that anti-GlcNAc/anti-myosin mAb 3.B6 from a rheumatic carditis patient was
      cytotoxic for human endothelial cell lines and reacted with human valvular
      endothelium and underlying basement membrane. Reactivity of mAb 3.B6 with the
      valve was inhibited by human cardiac myosin > laminin > GlcNAc. The mAb 3.B6
      epitopes were localized in fragments of human cardiac myosin, including heavy
      meromyosin (HMM), the S1 subfragment, and two light meromyosin (LMM) peptides
      containing amino acid sequences KEALISSLTRGKLTYTQQ (LMM 1) and SERVQLLHSQNTSLINQK
      (LMM 33). A novel feature of mAb 3.B6 was its reactivity with the extracellular
      matrix protein laminin, which may explain its reactivity with the valve surface.
      A laminin A-chain peptide (HTQNT) that includes homology to LMM33 inhibited the
      reactivity of mAb 3.B6 with human valve. These data support the hypothesis that
      cross-reactive antibodies in rheumatic carditis cause injury at the endothelium
      and underlying matrix of the valve.

PMID- 10903339
TI  - Junctional communication of pancreatic beta cells contributes to the control of
      insulin secretion and glucose tolerance.
AB  - Proper insulin secretion requires the coordinated functioning of the numerous
      beta cells that form pancreatic islets. This coordination depends on a network of
      communication mechanisms whereby beta cells interact with extracellular signals
      and adjacent cells via connexin channels. To assess whether connexin-dependent
      communication plays a role in vivo, we have developed transgenic mice in which
      connexin 32 (Cx32), one of the vertebrate connexins found in the pancreas, is
      expressed in beta cells. We show that the altered beta-cell coupling that results
      from this expression causes reduced insulin secretion in response to
      physiologically relevant concentrations of glucose and abnormal tolerance to the
      sugar. These alterations were observed in spite of normal numbers of islets,
      increased insulin content, and preserved secretory response to glucose by
      individual beta cells. Moreover, glucose-stimulated islets showed improved
      electrical synchronization of these cells and increased cytosolic levels of
      Ca(2+). The results show that connexins contribute to the control of beta cells
      in vivo and that their excess is detrimental for insulin secretion.

PMID- 10903341
TI  - Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of
      morbid obesity.
AB  - By integrating an agonist satiety signal, provided by alpha-melanocyte
      stimulating hormone (alpha-MSH), and an antagonist signal, provided by agouti
      related protein (AGRP), the melanocortin-4 receptor (MC4-R) is a key element in
      the hypothalamic control of food intake. Inactivation of the gene encoding this G
      protein-coupled receptor causes obesity in mice. In humans, frameshift mutations
      in MC4-R cause an early-onset dominant form of obesity in two families. In this
      study we find a high frequency (4%) of rare heterozygous MC4-R mutations in a
      large population of morbidly obese patients. No such mutations were found in
      controls. By analyzing the phenotypes of the probands carrying these mutations,
      we demonstrate that these patients display a common, nonsyndromic form of
      obesity. Interestingly, functional analysis of the mutant receptors indicates
      that obesity-associated defects in MC4-R range from loss of function to
      constitutive activation. Transmission of these mutations in the families of the
      carriers indicates a variable expressivity that is not related to the functional
      severity of the mutations. This variable expressivity of MC4-R-associated obesity
      is not due to variations in genes for alpha-MSH or AGRP. Taken together, these
      results demonstrate that MC4-R mutations are a frequent but heterogeneous genetic
      cause of morbid obesity.

PMID- 10903340
TI  - Retroviral gene therapy with an immunoglobulin-antigen fusion construct protects
      from experimental autoimmune uveitis.
AB  - Immunoglobulins can serve as tolerogenic carriers for antigens, and B cells can
      function as tolerogenic antigen-presenting cells. We used this principle to
      design a strategy for gene therapy of experimental autoimmune uveitis, a cell
      mediated autoimmune disease model for human uveitis induced with the uveitogenic
      interphotoreceptor retinoid-binding protein (IRBP). A retroviral vector was
      constructed containing a major uveitogenic IRBP epitope in frame with mouse IgG1
      heavy chain. This construct was used to transduce peripheral B cells, which were
      infused into syngeneic recipients. A single infusion of transduced cells, 10 days
      before uveitogenic challenge, protected mice from clinical disease induced with
      the epitope or with the native IRBP protein. Protected mice had reduced antigen
      specific responses, but showed no evidence for a classic Th1/Th2 response shift
      or for generalized anergy. Protection was not transferable, arguing against a
      mechanism dependent on regulatory cells. Importantly, the treatment was
      protective when initiated 7 days after uveitogenic immunization or concurrently
      with adoptive transfer of primed uveitogenic T cells. We suggest that this form
      of gene therapy can induce epitope-specific protection not only in naive, but
      also in already primed recipients, thus providing a protocol for treatment of
      established autoimmunity.

PMID- 10903343
TI  - Dominant and recessive inheritance of morbid obesity associated with melanocortin
      4 receptor deficiency.
AB  - Over 20 severely obese subjects in 11 independent kindreds have been reported to
      have pathogenic heterozygous mutations in the gene encoding the melanocortin 4
      receptor (MC4R), making this the most common known monogenic cause of human
      obesity. To date, the detailed clinical phenotype of this dominantly inherited
      disorder has not been defined, and no homozygous subjects have been described. We
      determined the nucleotide sequence of the entire coding region of the MC4R gene
      in 243 subjects with severe, early-onset obesity. A novel two-base pair GT
      insertion in codon 279 was found in two unrelated subjects, and four novel
      missense mutations, N62S, R165Q, V253I, C271Y, and one mutation (T112M) reported
      previously were found in five subjects. N62S was found in homozygous form in five
      children with severe obesity from a consanguineous pedigree. All four
      heterozygous carriers were nonobese. Several features of the phenotype, e.g.
      hyperphagia, tendency toward tall stature, hyperinsulinemia, and preserved
      reproductive function, closely resemble those reported previously in Mc4r knock
      out mice. In addition, a marked increase in bone mineral density was seen in all
      affected subjects. In transient transfection assays, the N62S mutant receptor
      showed a responsiveness to alphaMSH that was intermediate between the wild-type
      receptor and mutant receptors carrying nonsense and missense mutations associated
      with dominantly inherited obesity. Thus MC4R mutations result in a syndrome of
      hyperphagic obesity in humans that can present with either dominant or recessive
      patterns of inheritance.

PMID- 10903342
TI  - Erythroid progenitors differentiate and mature in response to endogenous
      erythropoietin.
AB  - We reported previously that stimulation of glycoprotein 130 (gp130) by a
      combination of human IL-6 and soluble IL-6 receptor (sIL-6R) could support
      proliferation, differentiation, and terminal maturation of erythroid cells in the
      absence of erythropoietin (EPO) from human CD34(+) cells in culture with stem
      cell factor (SCF). This observation suggested that differentiation of
      hematopoietic stem/progenitor cells to erythroid cells progressed according to an
      intrinsic program and that EPO receptor (EPOR) could be replaced by other
      cytokine receptors. In other words, EPOR appeared to be dispensable for
      erythropoiesis. Here we examined the role of EPOR in erythropoiesis stimulated by
      SCF, sIL-6R, and IL-6. Surprisingly, reduction of EPOR expression using antisense
      oligodeoxynucleotides suppressed erythropoiesis stimulated not only by SCF and
      EPO, but also by SCF, sIL-6R, and IL-6. EPO mRNA was detected in erythroid cells
      but not myeloid cells cultured in the presence of SCF, sIL-6R, and IL-6.
      Furthermore, high concentrations of anti-EPO-neutralizing antibody abrogated
      erythropoiesis in cultures without exogenous EPO. Based on these results, we
      suggest that erythroid progenitors themselves secrete EPO and that they have the
      potential to differentiate and mature in response to this endogenous EPO.

PMID- 10903344
TI  - Congenital sucrase-isomaltase deficiency arising from cleavage and secretion of a
      mutant form of the enzyme.
AB  - Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive human
      intestinal disorder that is clinically characterized by fermentative diarrhea,
      abdominal pain, and cramps upon ingestion of sugar. The symptoms are the
      consequence of absent or drastically reduced enzymatic activities of sucrase and
      isomaltase, the components of the intestinal integral membrane glycoprotein
      sucrase-isomaltase (SI). Several known phenotypes of CSID result from an altered
      posttranslational processing of SI. We describe here a novel CSID phenotype, in
      which pro-SI undergoes an unusual intracellular cleavage that eliminates its
      transmembrane domain. Biosynthesis of pro-SI in intestinal explants and in cells
      transfected with the SI cDNA of this phenotype demonstrated a cleavage occurring
      within the endoplasmic reticulum due to a point mutation that converts a leucine
      to proline at residue 340 of isomaltase. Cleaved pro-SI is transported to and
      processed in the Golgi apparatus and is ultimately secreted into the exterior
      milieu as an active enzyme. To our knowledge this is the first report of a
      disorder whose pathogenesis results not from protein malfolding or mistargeting,
      but from the conversion of an integral membrane glycoprotein into a secreted
      species that is lost from the cell surface.

PMID- 10903345
TI  - Adenosine formed by 5'-nucleotidase mediates tubuloglomerular feedback.
AB  - Nephron function is stabilized by tubuloglomerular feedback (TGF). TGF operates
      within the juxtaglomerular apparatus, sensing changes in tubular flow and
      eliciting compensatory changes in single nephron GFR (SNGFR). The mediator(s) of
      TGF remains unconfirmed. One theory is that ATP consumed in active transport by
      the macula densa leads to formation of adenosine, which causes glomerular
      vasoconstriction. We performed micropuncture in rats to test this hypothesis.
      Adenosine activity was manipulated by microperfusing nephrons with adenosine A1
      receptor blocker, A1-agonist, or 5'-nucleotidase inhibitor. Effects on TGF were
      characterized by changes in TGF efficiency (the compensation for small
      perturbations in tubular flow) and by changes in the maximum range over which TGF
      can cause SNGFR to change. These data were further applied to generate TGF
      profiles [SNGFR versus late proximal flow (V(LP))]. TGF efficiency was
      significantly reduced by blocking A1-receptors. TGF efficiency, TGF range, and
      the slope of the TGF profile (DeltaSNGFR/DeltaV(LP)) were all significantly
      reduced by blocking 5'-nucleotidase. When adenosine activity was clamped by
      combining 5'-nucleotidase inhibitor with A1-agonist to determine whether TGF
      requires adenosine to be present or to fluctuate, the TGF slope was reduced by
      83%, indicating that adenosine activity must fluctuate for normal TGF to occur
      and that adenosine is a mediator of TGF.

PMID- 10903346
TI  - Loss of function and inhibitory effects of human CSX/NKX2.5 homeoprotein
      mutations associated with congenital heart disease.
AB  - CSX/NKX2.5 is an evolutionarily conserved homeodomain-containing (HD-containing)
      transcription factor that is essential for early cardiac development. Recently,
      ten different heterozygous CSX/NKX2.5 mutations were found in patients with
      congenital heart defects that are transmitted in an autosomal dominant fashion.
      To determine the consequence of these mutations, we analyzed nuclear
      localization, DNA binding, transcriptional activation, and dimerization of mutant
      CSX/NKX2.5 proteins. All mutant proteins were translated and located to the
      nucleus, except one splice-donor site mutant whose protein did not accumulate in
      the cell. All mutants that had truncation or missense mutations in the HD had
      severely reduced DNA binding activity and little or no transcriptional activation
      function. In contrast, mutants with intact HDs exhibit normal DNA binding to the
      monomeric binding site but had three- to ninefold reduction in DNA binding to the
      dimeric binding sites. HD missense mutations that preserved homodimerization
      ability inhibited the activation of atrial natriuretic factor by wild-type
      CSX/NKX2.5. Although our studies do not characterize the genotype-phenotype
      relationship of the ten human mutations, they identify specific abnormalities of
      CSX/NKX2.5 function essential for transactivation of target genes.

PMID- 10903348
TI  - Evidence for angiotensin II type 2 receptor-mediated cardiac myocyte enlargement
      during in vivo pressure overload
AB  - The pathophysiological roles of the angiotensin II type 2 receptor (AT(2)) in
      cardiac hypertrophy remain unclear. By the targeted deletion of mouse AT(2) we
      were able to prevent the left ventricular hypertrophy resulting from pressure
      overload, while cardiac contractile functions remained normal. This implies that
      AT(2) is a mediator of cardiac hypertrophy in response to increased blood
      pressure. The effects of AT(2) deletion were independent of activation of
      embryonic genes for cardiac hypertrophy. However, p70(S6k), one of the key
      factors in cardiac hypertrophy, was markedly and specifically reduced in the
      ventricles of Agtr2(-)/Y mice. We propose that p70(S6k) plays a major role in
      AT(2)-mediated ventricular hypertrophy. This article may have been published
      online in advance of the print edition. The date of publication is available from
      the JCI website, http://www.jci.org.

PMID- 10903347
TI  - A selective inhibitor of the osteoclastic V-H(+)-ATPase prevents bone loss in
      both thyroparathyroidectomized and ovariectomized rats.
AB  - A potent and selective inhibitor of the osteoclastic V-H(+)-ATPase, (2Z,4E)-5
      (5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6, 6-pentamethylpiperidin-4-yl)-2,4
      pentadienamide (SB 242784), was evaluated in two animal models of bone
      resorption. SB 242784 completely prevented retinoid-induced hypercalcemia in
      thyroparathyroidectomized (TPTX) rats when administered orally at 10 mg/kg. SB
      242784 was highly efficacious in the prevention of ovariectomy-induced bone loss
      in the rat when administered orally for 6 months at 10 mg/kg/d and was partially
      effective at 5 mg/kg/d. Its activity was demonstrated by measurement of bone
      mineral density (BMD), biochemical markers of bone resorption, and
      histomorphometry. SB 242784 was at least as effective in preventing bone loss as
      an optimal dose of estrogen. There were no adverse effects of compound
      administration and no effects on kidney function or urinary acidity. Selectivity
      of the inhibitor was further studied using an in situ cytochemical assay for
      bafilomycin-sensitive V-H(+)-ATPase using sections of osteoclastoma and numerous
      other tissues. SB 242784 inhibited the osteoclast enzyme at 1,000-fold lower
      concentrations than enzymes in any of the other tissues evaluated. SB 242784
      demonstrates the utility of selective inhibition of the osteoclast V-H(+)-ATPase
      as a novel approach to the prevention of bone loss in humans.

PMID- 10903349
TI  - Tin compounds and major trace metal elements in organotin-poisoned Patient's
      urine and blood measured by gas chromatography-flame photometric detector and
      inductively coupled plasma-mass spectrometry.

PMID- 10903350
TI  - Zinc-protoporphyrin determination as a screening test for lead-exposure in
      childhood.

PMID- 10903351
TI  - Partitioning coefficients of organochlorine pesticides between mother blood serum
      and umbilical blood serum.

PMID- 10903352
TI  - Effect of tea and coffee consumption on serum uric acid levels by liquid
      chromatographic and uricase methods.

PMID- 10903353
TI  - Comparison of soxhlet, shaking, and microwave assisted extraction techniques for
      determination of PCB congeners in a marine sediment.

PMID- 10903354
TI  - Determination of lead sources in water samples using isotope ratios.

PMID- 10903355
TI  - Distribution and removal of cadmium and lead in a constructed wetland receiving
      urban runoff.

PMID- 10903356
TI  - Scavenging potential of hydrophytes for copper removal from textile dye
      wastewaters.

PMID- 10903357
TI  - Cypermethrin and deltamethrin concentration and contamination in pulses from
      application to jute sacks.

PMID- 10903358
TI  - Comparison of elemental composition and solubility in the zinc hyperaccumulator
      Thlaspi caerulescens with the non-hyperaccumulator Thlaspi ochroleucum.

PMID- 10903359
TI  - Comparative evaluation of the levels of some antioxidant enzymes and lipid
      peroxidation in different fish species in two rivers in the Western Niger delta.

PMID- 10903360
TI  - Effects of rare earth metal ions and their EDTA complexes on antioxidant enzymes
      of fish liver.

PMID- 10903361
TI  - Quantitative structure-toxicity relationships for derivates of benzanilides to
      Daphnia magna.

PMID- 10903362
TI  - Toxicity of N-containing heterocyclic aromatic compounds and their utilization
      for growth by a few purple non-sulfur bacteria.

PMID- 10903363
TI  - Acute toxicity of the fungicide copper oxychloride to the freshwater prawn
      Macrobrachium rosenbergii De Man.

PMID- 10903364
TI  - Petroleum hydrocarbon pollution in sharks in the Arabian Gulf.

PMID- 10903365
TI  - Interspecies modeling of narcotics toxicity to aquatic animals.

PMID- 10903366
TI  - Enchytraeid Enchytraeus crypticus as a test organism for crude oil contamination
      of soil.

PMID- 10903367
TI  - Molecular evolution of nitrogen fixation: the evolutionary history of the nifD,
      nifK, nifE, and nifN genes.
AB  - The pairs of nitrogen fixation genes nifDK and nifEN encode for the alpha and
      beta subunits of nitrogenase and for the two subunits of the NifNE protein
      complex, involved in the biosynthesis of the FeMo cofactor, respectively.
      Comparative analysis of the amino acid sequences of the four NifD, NifK, NifE,
      and NifN in several archaeal and bacterial diazotrophs showed extensive sequence
      similarity between them, suggesting that their encoding genes constitute a novel
      paralogous gene family. We propose a two-step model to reconstruct the possible
      evolutionary history of the four genes. Accordingly, an ancestor gene gave rise,
      by an in-tandem paralogous duplication event followed by divergence, to an
      ancestral bicistronic operon; the latter, in turn, underwent a paralogous operon
      duplication event followed by evolutionary divergence leading to the ancestors of
      the present-day nifDK and nifEN operons. Both these paralogous duplication events
      very likely predated the appearance of the last universal common ancestor. The
      possible role of the ancestral gene and operon in nitrogen fixation is also
      discussed.

PMID- 10903368
TI  - Are RNA viruses adapting or merely changing?
AB  - RNA viruses and retroviruses fix substitutions approximately 1 million-fold
      faster than their hosts. This diversification could represent an inevitable drift
      under purifying selection, the majority of substitutions being phenotypically
      neutral. The alternative is to suppose that most fixed mutations are beneficial
      to the virus, allowing it to keep ahead of the host and/or host population. Here,
      relative sequence diversification of different proteins encoded by viral genomes
      is found to be linear. The examples encompass a wide variety of retroviruses and
      RNA viruses. The smoothness of relative divergence spans quasispeciation
      following clonal infection, to variation among different isolates of the same
      virus, to viruses from different species or those associated with different
      diseases, indicating that the majority of fixed mutations likely reflects drift.
      This held for both mammalian and plant viruses, indicating that adaptive immunity
      doesn't necessarily shape the relative accumulation of amino acid substitutions.
      When compared to their hosts RNA viruses evolution appears conservative.

PMID- 10903369
TI  - An attempt to measure the patchwork pattern observed among alleles at major
      histocompatibility complex loci.
AB  - By means of simulations and DNA sequence analyses, standardized identity excess
      (a measure of linkage disequilibrium) between segregating nucleotide sites was
      studied as an effort to quantify the patchwork pattern among alleles of the major
      histocompatibility complex loci. It was found that the pattern under selective
      neutrality, and/or no intralocus recombination does not fit the observed pattern
      based on DNA sequences. However, the intensity and type of selection and the rate
      of recombination are difficult to estimate by comparing simulation results with
      the observed pattern.

PMID- 10903370
TI  - Phylogeny of ultra-rapidly evolving dinoflagellate chloroplast genes: a possible
      common origin for sporozoan and dinoflagellate plastids.
AB  - Complete chloroplast 23S rRNA and psbA genes from five peridinin-containing
      dinoflagellates (Heterocapsa pygmaea, Heterocapsa niei, Heterocapsa rotun-data,
      Amphidinium carterae, and Protoceratium reticulatum) were amplified by PCR and
      sequenced; partial sequences were obtained from Thoracosphaera heimii and
      Scrippsiella trochoidea. Comparison with chloroplast 23S rRNA and psbA genes of
      other organisms shows that dinoflagellate chloroplast genes are the most
      divergent and rapidly evolving of all. Quartet puzzling, maximum likelihood,
      maximum parsimony, neighbor joining, and LogDet trees were constructed. Intersite
      rate variation and invariant sites were allowed for with quartet puzzling and
      neighbor joining. All psbA and 23S rRNA trees showed peridinin-containing
      dinoflagellate chloroplasts as monophyletic. In psbA trees they are related to
      those of chromists and red algae. In 23S rRNA trees, dinoflagellates are always
      the sisters of Sporozoa (apicomplexans); maximum likelihood analysis of
      Heterocapsa triquetra 16S rRNA also groups the dinoflagellate and sporozoan
      sequences, but the other methods were inconsistent. Thus, dinoflagellate
      chloroplasts may actually be related to sporozoan plastids, but the possibility
      of reproducible long-branch artifacts cannot be strongly ruled out. The results
      for all three genes fit the idea that dinoflagellate chloroplasts originated from
      red algae by a secondary endosymbiosis, possibly the same one as for chromists
      and Sporozoa. The marked disagreement between 16S rRNA trees using different
      phylogenetic algorithms indicates that this is a rather poor molecule for
      elucidating overall chloroplast phylogeny. We discuss possible reasons why both
      plastid and mitochondrial genomes of alveolates (Dinozoa, Sporozoa and
      Ciliophora) have ultra-rapid substitution rates and a proneness to unique genomic
      rearrangements.

PMID- 10903371
TI  - Direct calculation of a tree length using a distance matrix.
AB  - Comparative studies of tree-building methods have shown minimum evolution to be
      in general an accurate criterion for selecting a true tree. To improve the use of
      this criterion, this paper proposes a method for rapidly and directly calculating
      a length of a dichotomous tree without having to resort to branch length
      calculations. This direct calculation (DC) method applies to the complete final
      topology, giving equal importance to each branch after a dichotomy. According to
      this method, the tree length S(DC) is S(DC) = sigma(i) sigma(j)(D(ij)/2(B(ij))) =
      (sigma(i<j) sigma D(ij)2(Bmax-B(ij)))/2(Bmax)(-1) where D(ij) is the observed
      distance between taxa i and j, B(ij) is the number of branches connecting i and
      j, Bmax is the greatest B(ij) in the tree, and the powers of two are due to the
      dichotomy of the tree. This tree length expression may be used as a rapid method
      for selecting the shortest tree from a set of hypothetical or subobtimal trees.

PMID- 10903373
TI  - Comparative genomics of mitochondrial DNA in Drosophila simulans.
AB  - The current study compares the nucleotide variation among 22 complete
      mitochondrial genomes of the three distinct Drosophila simulans haplotypes with
      intron 1 of the alcohol dehydrogenase-related locus. This is the first study to
      investigate the sequence variation of multiple complete mitochondrial genomes
      within distinct mitochondrial haplotypes of a single species. Patterns of
      variation suggest distinct forces are influencing the evolution of mitochondrial
      DNA (mtDNA) and autosomal DNA in D. simulans. First, there is little variation
      within each mtDNA haplotype but strong differentiation among them. In contrast,
      there is no support for differentiation of the mitochondrial haplotypes at the
      autosomal locus. Second, there is a significant deficiency of mitochondrial
      variation in each haplotype relative to the autosomal locus. Third, the ratio of
      nonsynonymous to synonymous substitutions is not equal in all branches of the
      well-resolved phylogeny. There is an excess of nonsynonymous substitutions
      relative to synonymous substitutions within each D. simulans haplotype. This
      result is similar to that previously observed within the mtDNA of distinct
      species. A single evolutionary force may be causally linked to the observed
      patterns of mtDNA variation-a rickettsia-like microorganism, Wolbachia pipientis,
      which is known to directly influence mitochondrial evolution but have a less
      direct influence on autosomal loci.

PMID- 10903372
TI  - Comparative genomics of mitochondrial DNA in members of the Drosophila
      melanogaster subgroup.
AB  - In this study, a comparative genomics approach is employed to investigate the
      forces that shape evolutionary change in the mitochondrial DNA (mtDNA) of members
      of the Drosophila melanogaster subgroup. This approach facilitates
      differentiation of the patterns of variation resulting from processes acting at a
      higher level from those acting on a single gene. The mitochondrial genomes of
      three isofemale lines of D. simulans (siI, -II, and -III), two of D. melanogaster
      (Oregon R and a line from Zimbabwe), and D. mauritiana (maI and -II), and one of
      D. sechellia were sequenced and compared with that derived from D. yakuba. Data
      presented here indicate that at least three broad mechanisms shape the
      evolutionary dynamics of mtDNA in these taxa. The first set of mechanisms is
      intrinsic to the molecule. Dominant processes may be interpreted as selection for
      an increased rate of replication of the mtDNA molecule, biases in DNA repair, and
      differences in the pattern of nucleotide substitution among strands. In the genes
      encoded on the major strand (62% of the coding DNA) changes to or from C
      predominate, whereas on the minor changes to or from G predominate. The second
      set of mechanisms affects distinct lineages. There are evolutionary rate
      differences among lineages, possibly owing to population demographic changes or
      changes in mutational biases. This is supported by the heterogeneity found in
      synonymous, nonsynonymous, and silent substitutions. The third set of mechanisms
      differentially affects distinct genes. A maximum-likelihood sliding-window
      analysis detected four disjunct regions that have a significantly different
      nucleotide substitution process from that derived from the complete sequence.
      These data show the potential for comparative genomics to tease apart subtle
      forces that shape the evolution of DNA.

PMID- 10903374
TI  - Sequence, organization, and evolution of Rh50 glycoprotein genes in nonhuman
      primates.
AB  - The human RHAG locus encodes Rh50 glycoprotein, a polytopic protein that
      modulates expression of Rh antigens carried by Rh30 polypeptides. Rh50 is almost
      invariant, whereas Rh30 shows high polymorphism. To assess the relative
      conservation and phylogenetic relationship of RHAG genes, we characterized their
      protein expression, transcript structure, genomic organization, and noncoding
      regions (promoter and introns) in seven nonhuman primate species. Western blot
      showed that only ape Rh50 glycoproteins are recognized by the antibody 2D10
      specific for the human counterpart. Analysis of RHAG gene and its transcript
      showed a high degree of sequence identity and features of interspecific
      diversity. The nonhuman primate RHAG genes are highly similar in promoter region
      and identical in exon-intron organization. Genomic sequencing identified one
      retro-transposon-like element in intron 2 and three types of Alu elements in
      intron 4 and 9, with varying copies of minisatellites. Reconstruction of coding
      and noncoding sequence trees revealed concordances and discordances with regard
      to the branching of RHAG-like genes in higher primates. A joined tree of Rh50
      glycoproteins and Rh30 polypeptides shows that the former evolved at a rate about
      two times slower than the latter. Statistical tests demonstrated that at least a
      portion of the RHAG gene was subjected to a positive selection during evolution
      of anthropoids.

PMID- 10903375
TI  - Evolutionary patterns of gene families generated in the early stage of
      vertebrates.
AB  - In this paper we have analyzed 49 vertebrate gene families that were generated in
      the early stage of vertebrates and/or shortly before the origin of vertebrates,
      each of which consists of three or four member genes. We have dated the first
      (T(1)) and second (T(2)) gene duplications of 26 gene families with 3 member
      genes. The means of T(1) (594 mya) and T(2) (488 mya) are largely consistent to a
      well-cited version of two-round (2R) genome duplication theory. Moreover, in most
      cases, the time interval between two successive gene duplications is large enough
      that the fate of duplicate genes generated by the first gene duplication was
      likely to be determined before the second one took place. However, the
      phylogenetic pattern of 23 gene families with 4 members is complicated; only 5 of
      them are predicted by 2R model, but 11 families require an additional gene (or
      genome) duplication. For the rest (7 families), at least one gene duplication
      event had occurred before the divergence between vertebrate and Drosophila,
      indicating a possible misleading of the 4:1 rule (member gene ratio between
      vertebrates and invertebrates). Our results show that Ohno's 2R conjecture is
      valid as a working hypothesis for providing a most parsimonious explanation.
      Although for some gene families, additional gene duplication is needed, the
      credibility of the third genome duplication (3R) remains to be investigated.

PMID- 10903376
TI  - Nucleic acids for recognition and catalysis: landmarks, limitations, and looking
      to the future
AB  - Combinatorial selection of nucleic acids has led to the discovery of novel
      ligands and catalysts that have implications for both chemistry and medicine. In
      the context of combinatorial chemistry, degenerate syntheses of nucleic acid
      libraries readily generate as many as 1015 different molecules in which a small
      percentage exhibit interesting binding and/or catalytic properties. The primary
      advantage of nucleic acids is that library coding is an intrinsic property;
      sequential composition directly determines the activity. At low temperatures, the
      sequential composition of single stranded nucleic acids governs folding into
      irregular tertiary structures resulting in interesting activities. At higher
      temperatures, the same structures are unfolded and decoded by polymerases to
      reveal sequential information. The use of PCR (polymerase chain reaction) permits
      amplification and thus enrichment of the selected activity which is then
      regenerated chemi-enzymatically. Iterative selection and amplification result in
      one of the highest throughput screens conceivable whereby each molecule encodes
      its own activity permitting the ultimate in parallel sampling. Finally, sequence
      information, and by extension the chemical composition, is obtained by simple
      sequencing techniques obviating the need for mass spectrometric deconvolution,
      parallel tagging, and/or large volumes needed for viral and cell culture. This
      review begins with an introduction of general concepts and considerations. The
      potential for nucleic acids to generate tight-binding ligands is of interest to
      structural biologists and medicinal chemists. The therapeutic implications to
      medicine are also touched upon. Since combinatorially selected nucleic acids and
      antibodies share many conceptual similarities, their respective advantages and
      limitations are compared. Theoretical and practical limitations for catalyst
      discovery are discussed along with the use of other chemical and physical
      approaches to address some current catalytic shortcomings. Finally some future
      directions are suggested.

PMID- 10903377
TI  - A merger of rational drug design and combinatorial chemistry: development and
      application of peptide secondary structure mimetics.
AB  - Recent efforts toward the development of peptide secondary structure mimetics at
      Molecumetics Ltd. for the discoveries of new drug candidates utilizing
      combinatorial chemistry with solid phase synthesis are described.

PMID- 10903378
TI  - Recombinant polyclonal antibody libraries.
AB  - We describe a technology for generating recombinant polyclonal antibody libraries
      (PCALs) that enables the creation and perpetuation of standardized mixtures of
      polyclonal whole antibodies specific for a multiantigen (or polyantigen).
      Therefore, this technology combines the advantages of targeting multiple
      antigenic determinants -- high avidity, low likelihood of antigen 'escape
      variants', and efficient mediation of effector functions, with the advantages of
      using monoclonal antibodies -- unlimited supply of standardized reagents and the
      availability of the genetic material for desired manipulations. The technology
      for generating recombinant polyclonal antibody libraries begins with the creation
      of phage display Fab (antibody) libraries. This is followed by selection of
      sublibraries with desired antigen specificities, and mass transfer of the
      variable region gene pairs of the selected sublibraries to a mammalian expression
      vector for generation of libraries of polyclonal whole antibodies. We review here
      our experiments for selection of phage display antibody libraries against
      microbes and tumor cells, as well as the recent literature on the selection of
      phage display antibody libraries to multiantigen targets.

PMID- 10903379
TI  - Redistribution in combinatorial synthesis. A theoretical approach.
AB  - In modified versions of the split-mix method, the conventional solid support
      resin was replaced by labeled macroscopic support units in order to produce
      individual compounds in multi milligram quantities while the high productivity of
      the original procedure is preserved. Recently it has also been shown that tagging
      the units is unnecessary. Omission of the tags is possible if (i) the unlabeled
      support units are arranged into spatially ordered groups and the relative spatial
      arrangement of the units is maintained during the chemical reactions (ii) the
      support units are redistributed between the reaction steps according to a
      predetermined pattern permitted by the combinatorial redistribution rule and
      (iii) the sorting process is simulated by a computer that can trace the synthetic
      history of each support unit. Different kinds of solid support units, formation
      of spatially ordered groups, sorting devices and basic redistribution patterns
      (serial, semi-parallel and parallel) are discussed. It is also shown that
      particularly the semi-parallel and the parallel redistribution assure fast
      sorting.

PMID- 10903380
TI  - PCR/SSCP detects reliably and efficiently DNA sequence variations in large scale
      screening projects.
AB  - A simple and fast method with high reliability is necessary for the
      identification of mutations, polymorphisms and sequence variants (MPSV) within
      many genes and many samples, e.g. for clarifying the genetic background of
      individuals with multifactorial diseases. Here we review our experience with the
      polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP)
      analysis to identify MPSV in a number of genes thought to be involved in the
      pathogenesis of multifactorial neurological disorders, including autoimmune
      diseases like multiple sclerosis (MS) and neurodegenerative disorders like
      Parkinson s disease (PD). The method is based on the property of the DNA that the
      electrophoretic mobility of single stranded nucleic acids depends not only on
      their size but also on their sequence. The target sequences were amplified,
      digested into fragments ranging from 50-240 base pairs (bp), heat-denatured and
      analysed on native polyacrylamide (PAA) gels of different composition. The
      analysis of a great number of different PCR products demonstrates that the
      detection rate of MPSV depends on the fragment lengths, the temperature during
      electrophoresis and the composition of the gel. In general, the detection of MPSV
      is neither influenced by their location within the DNA fragment nor by the type
      of substitution, i.e., transitions or transversions. The standard PCR/SSCP system
      described here provides high reliability and detection rates. It allows the
      efficient analysis of a large number of DNA samples and many different genes.

PMID- 10903381
TI  - Rational drug design and high-throughput techniques for RNA targets.
AB  - RNA molecules are the only known molecules which possess the double property of
      being depository of genetic information, like DNA, and of displaying catalytic
      activities, like protein enzymes. RNA molecules intervene in all steps of gene
      expression and in many other biological activities. Like proteins, RNAs achieve
      those biological functions by adopting intricate three-dimensional folds and
      architectures. Further, as in protein sequences, RNA sequences contain signatures
      specific for three-dimensional motifs which participate in recognition and
      binding. In regulatory pathways, RNA molecules exist in equilibria between
      transient structures differentially stabilized by effectors such as proteins or
      cofactors. Therefore, RNA molecules display their potential as drug targets on
      different levels, namely in three-dimensional folds, in structural equilibria and
      in RNA-protein interfaces. Several examples will be described together with the
      already available techniques for combinatorial synthesis and high-throughput
      screening of potential drug and target RNA molecules.

PMID- 10903382
TI  - Identification of differential gene expression by high throughput analysis.
AB  - High throughput analysis of differential gene expression is a powerful tool that
      can be applied to many areas in molecular cell biology, including
      differentiation, development, physiology, and pharmacology. In recent years, a
      variety of techniques have been developed to analyze differential gene
      expression, including comparative expressed sequence tag sequencing, differential
      display, representational difference analysis, cDNA or oligonucleotide arrays,
      and serial analysis of gene expression. This review explains the technologies,
      their scopes, impact on science, as well as their costs and possible limitations.
      The application of differential display is presented as a tool to identify genes
      induced by darkness or yellowing process in rice leaves.

PMID- 10903384
TI  - Therapeutic radiopharmaceuticals.
AB  - A variety of radiopharmaceuticals have been introduced for the internal therapy
      of malignant and inflammatory lesions in nuclear medicine. In order to destroy
      the diseased tissues radionuclides with high linear energy transfer (LET) such as
      beta, alpha, Auger or low energy conversion electron emitters are needed. The
      range of beta particles is in mm's so they are effective for large tumors. The
      range of alpha particles is short, only a few cell diameters. Thus, they are
      effective in treating circulating malignant cells and micrometastases. The range
      of Auger and conversion electrons is <0.1 micro m. They are very effective in
      cell killing when they are carried across cell membrane into the nucleus to
      damage DNA. Appropriate ions, molecules and particles are labelled with such
      radionuclides and used as radiopharmaceuticals in many different applications.
      For an effective dose to be delivered high target to non target ratios must be
      attained. Monoclonal antibodies to specific antigens expressed on tumor cells
      have been developed to increase the uptake by malignant tissues by specific
      accumulation. Radiolabelled peptides such as somatostatin, small molecules such
      as metaiodo-benzylguanidine (MIBG) and many different nano-and micro-particles
      have been investigated. The effectiveness of therapy can be increased by direct
      locoregional administration of the radiopharmaceutical. This way the radiation
      effects are confined locally and the normal tissues are spared from radiation
      effects. In this review article selection criteria and characteristics of
      radionuclides and carrier ions, molecules and particles for various therapeutic
      applications will be discussed, including mainly the recent developments.

PMID- 10903385
TI  - Current developments in single photon radiopharmaceuticals for tumor imaging.
AB  - Development of peptides and amino acids labeled with single photon gamma emitters
      has promoted a large number of investigations in nuclear medicine especially for
      tumor imaging. Radiolabeled peptides have several advantages over antibodies
      mainly related to immunogenicity and size. Tumor localization and total body
      clearance of peptides are more rapid compared to antibodies. Recently, several
      somatostatin analogues labeled with Tc-99m have been studied by several different
      investigators. In-111 labeled lanreotide (Mauritus) was reported to be highly
      successful in localization of neuroendocrine tumors. A synthetic amino acid,
      alpha methyl tyrosine labeled with I-123 was shown to be transported to tumors by
      a carrier mediated system. Development of a glucose analog labeled with a single
      photon emitting radionuclide and meeting the structural requirements for
      hexokinase reaction and phosphorylation have not yet been possible. However, it
      has been possible to synthesize chemically stable single photon glucose analogues
      interacting with glut(s), glucose transporters.

PMID- 10903386
TI  - Potential use of radiolabeled glucuronide prodrugs with auger and/or alpha
      emitters in combined chemo- and radio-therapy of cancer.
AB  - Nowadays, the scientists from different disciplines have focused their attentions
      to new anticancer drug design for cancer chemotherapy. An effective anticancer
      drug should ensure the selective drug incorporation into the targeted tumor cells
      without principally incorporation into the normal cells. So, the targeted tumor
      cells can selectively be damaged by the cytotoxic effectiveness of the drug. The
      basic principles of drug design have involved "prodrug" concept, which means a
      chemical agent which is not itself active as an anticancer drug, but it can be
      transformed to an active form after its administration. Prodrugs can finally be
      activated onto the tumor cells by some kind of enzymes. In this context, the
      activation of glucuronide prodrugs by b-glucuronidase have a large potential
      applications in cancer chemotherapy. On the other hand, combined chemo- and radio
      therapy of cancer (CCRTC) concept aims to combine the cytotoxicity of an aglycone
      with the radiotoxicity of an appropriate radionuclide on the same prodrug. So,
      the cytotoxic and radiotoxic effectiveness' will be able to be concentrated into
      the same tumor cell to increase obviously its damage. For experimental
      realization of this concept an effective anticancer prodrug should be
      radiolabeled with a radionuclide having high level of radiotoxic effectiveness
      such as Auger and/or alpha-emitter radionuclides. Iodine-125 and astatine-211 are
      very interesting radionuclides as being effective Auger and/or alpha-emitters.
      Briefly, the glucuronide prodrugs radiolabeled with iodine-125 or astatine-211
      promise to be designed very effective anticancer agents in the future
      applications of cancer chemotherapy.

PMID- 10903387
TI  - Nicotinic acetylcholine receptors and imaging.
AB  - In vivo imaging techniques like positron emission tomography (PET) and single
      photon emission computed tomography (SPECT) offer the possibility to monitor
      human central nicotinic acetylcholine receptors (nAChRs) in a variety of central
      nervous system disorders. In the past, the only available PET radiotracer for
      imaging nAChRs in the human brain, [11C]-(-)-nicotine, suffered from a spectrum
      of not suitable properties for in vivo imaging. Current efforts are focused on
      the development of new, highly specific and highly selective radioligands based
      on different structural classes (e.g. nicotine, epibatidine, 3-pyridyl ether
      analogues) for central nAChRs. The most promising compounds are halogenated 3
      pyridyl ether compounds for imaging alpha 4 beta 2 nAChRs. But there is still a
      lack for radiotracers for other subtypes of nicotinic acetylcholine receptors
      being a promising area of interest.

PMID- 10903388
TI  - Radiopharmaceuticals for the visualization of infectious and inflammatory
      lesions.
AB  - Many radiopharmaceuticals have been introduced for the scintigraphic
      demonstration of infectious and inflammatory lesions and some of them are
      currently in clinical use. They can be classified into two major categories
      according to their specificity. Specific radiopharmaceuticals include in vitro
      labeled leukocytes, radio-labelled monoclonal antibodies, and receptor specific
      small proteins and peptides. Nonspecific radiopharmaceuticals include
      radiolabelled nanocolloids, liposomes, macromolecules such as human
      immunoglobulin, dextran and human serum albumin, various small molecules and
      ions. In this review article radiopharmaceuticals in their respective groups are
      discussed as to the efficacy, and other parameters such as the physical
      characteristics of the radionuclides used, radiochemistry involved, availability,
      cost and biodistribution, emphasizing recent developments.

PMID- 10903389
TI  - The effect of drugs on the labeling of blood elements with technetium-99m.
AB  - The influence of drugs on the labeling of red blood cells and plasma proteins
      with 99mTc has been reported. Any drug, which alters the labeling of the tracer,
      could be expected to modify the disposition of the radiopharmaceuticals. Red
      blood cells (RBC) labeled with technetium-99m (99mTc) are used for several
      evaluations in nuclear medicine. We have evaluated the effect of Thuya
      occidentalis, Peumus boldus and Nicotiana tabacum (tobacco) extracts on the
      labeling of RBC and plasma and cellular proteins with 99mTc. Blood was incubated
      with the drugs. Stannous chloride (SnCl2) solutions and 99mTc were added. Plasma
      (P) and blood cells (BC) were separated. The percentage of radioactivity (%ATI)
      bound to P and BC was determined. The %ATI on the plasma and cellular proteins
      was also evaluated by precipitation of P and BC samples with trichloroacetic acid
      (TCA) and isolation of soluble (SF) and insoluble (IF) fractions. The analysis of
      the results shows that there is a decrease in %ATI (from 97.64 to 75.89 percent)
      in BC with Thuya occidentalis extract. The labeling of RBC and plasma proteins
      can be decreased in presence of tobacco. This can be due either a direct or
      indirect effect (reactive oxygen species) of tobacco. The analysis of
      radioactivity in samples of P and BC isolated from samples of whole blood treated
      with Peumus boldus showed a rapid uptake of the radioactivity by blood cells in
      the presence of the Peumus boldus, whereas there was a slight decrease in the
      amount of 99mTc radioactivity in the TCA-insoluble fraction of plasma. This study
      shows that extracts of some medicinal plants can affect the radiolabeling of red
      blood cells with 99mTc using an in vitro technique.

PMID- 10903390
TI  - GABA uptake inhibitors. Design, molecular pharmacology and therapeutic aspects.
AB  - In the mid seventies a drug design programme using the Amanita muscaria
      constituent muscimol (7) as a lead structure, led to the design of guvacine (23)
      and (R)-nipecotic acid (24) as specific GABA uptake inhibitors and the isomeric
      compounds isoguvacine (10) and isonipecotic acid (11) as specific GABAA receptor
      agonists. The availability of these compounds made it possible to study the
      pharmacology of the GABA uptake systems and the GABAA receptors separately. Based
      on extensive cellular and molecular pharmacological studies using 23, 24, and a
      number of mono- and bicyclic analogues, it has been demonstrated that neuronal
      and glial GABA transport mechanisms have dissimilar substrate specificities. With
      GABA transport mechanisms as pharmacological targets, strategies for
      pharmacological interventions with the purpose of stimulating GABA
      neurotransmission seem to be (1) effective blockade of neuronal as well as glial
      GABA uptake in order to enhance the inhibitory effects of synaptically released
      GABA, or (2) selective blockade of glial GABA uptake in order to increase the
      amount of GABA taken up into, and subsequently released from, nerve terminals.
      The bicyclic compound (R)-N-Me-exo-THPO (17) has recently been reported as the
      most selective glial GABA uptake inhibitor so far known and may be a useful tool
      for further elucidation of the pharmacology of GABA transporters. In recent
      years, a variety of lipophilic analogues of the amino acids 23 and 24 have been
      developed, and one of these compounds, tiagabine (49) containing (R)-nipecotic
      acid (24) as the GABA transport carrier-recognizing structure element, is now
      marketed as an antiepileptic agent.

PMID- 10903391
TI  - Dopamine agonists in the treatment of Parkinson s disease past, present and
      future.
AB  - An attempt is made by the author to highlight the important events that laid the
      foundation of dopamine agonists as a treatment strategy for Parkinson s disease.
      This debilitating neurodegenerative disorder is long recognized as a result of
      progressive cell loss in the substantia nigra of the midbrain. The destruction of
      dopaminergic neurons with projections to the striatum results in the diminishing
      striatal dopamine levels. Anticholinergic drugs were once widely used to
      counteract the relative overactivity of cholinergic output from the basal ganglia
      and the strategy was only met with limited success. The discovery of dopamine
      depletion and the use of levodopa - a dopamine metabolic precursor, led the way
      to dopamine replacement therapy . The initial success with levodopa was soon
      overshadowed by the long-term side effects associated with levodopa. Many new
      drugs were developed with the hope to replace or strengthen the usefulness of
      levodopa. Apomorphine and ergot alkaloids have been around for some time; they
      are recently joined by newer dopamine agonists such as ropinirole and
      pramipexole. Each of these has its own characteristics and has occupied a place
      in the pharmacotherapy of Parkinson s disease. In this review older aporphines
      and ergot alkaloids are discussed first. More emphasis is directed to the side
      effect profiles, metabolism and pharmacokinetics in terms of their unique
      chemical structures. The most recent agonists will be briefly discussed before we
      move on to the future - the future of emerging novel classes of promising
      dopaminergic agonists.

PMID- 10903392
TI  - Conotoxins - new vistas for peptide therapeutics.
AB  - There are approximately 500 species of predatory cone snails within the genus
      Conus. They comprise what is arguably the largest single genus of marine animals
      alive today. It has been estimated that the venom of each Conus species has
      between 50 and 200 components. These highly constrained sulfur rich components or
      conotoxins represent a unique arsenal of neuropharmacologically active peptides
      that have been evolutionarily tailored to afford unprecedented and exquisite
      selectivity for a wide variety of ion-channel subtypes. Remarkable divergence
      occurs when cone snails speciate. Consequently, the complement of venom peptides
      in any one Conus species is distinct from that of any other species. Hence many
      thousands of peptides that modulate ion channel function are present within Conus
      venoms. Evolutionary pressures have afforded a "pre-optimized," structurally
      sophisticated library that has been "fine tuned" over 50 million years. The
      statistics associated with sampling such libraries bear testimony to the validity
      and feasibility of this strategy. Although approximately 100 conotoxin sequences
      have been published in the scientific literature, representing a mere 0.2 % of
      the estimated library size, this sample has already afforded a peptide of proven
      clinical utility and several pre-clinical leads for CNS disorders. Conus
      libraries represent a rich pharmacopoeia and the potential to "therapeutically
      mine" such a resource appears limitless. The paucity of synthetic methodologies
      necessary to achieve the regioisomeric folding patterns present in these native
      peptides precludes access to synthetic conotoxin libraries, further validating
      the overall "mining" strategy. In this article, we will present a pragmatic
      overview of the molecular diversity as well as the neurobiological mechanisms
      that define each major class of conotoxin.

PMID- 10903393
TI  - Drugs with estrogen-like potency and brain activity: potential therapeutic
      application for the CNS.
AB  - Numerous reports, ranging from molecular investigations to clinical studies,
      demonstrate the potency of estrogens to modulate brain function and their
      implications in schizophrenia and depression. Alterations of dopaminergic,
      cholinergic, GABAergic, glutamatergic and serotonergic neurotransmission through
      estrogen-mediated mechanisms have been consistently established. Moreover,
      studies using in vivo and in vitro models as well as epidemiological data suggest
      that estrogens provide neuroprotection of central nervous system (CNS) cells
      implicated in the etiology of neurodegenerative disorders such as Alzheimer s
      (AD) and Parkinson s (PD) diseases. Numerous genomic or non-genomic mechanisms of
      actions of estrogens in the brain have been documented implicating classical
      nuclear estrogen receptors as well as possible estrogen membrane receptors,
      antioxidant activity of steroids, their effect on fluidity as well as on
      antiapoptotic proteins and growth factors. Selective estrogen receptor modulators
      (SERMs) have estrogenic and/or antiestrogenic activity depending on the target
      tissue. Hence, SERMs have the same beneficial effect as estrogen in skeleton and
      cardiovascular systems but act as antagonists in breast and uterus. The finding
      of beneficial side effects of SERMs in the CNS might improve their risk-benefit
      ratio in traditional indications. In this review, we will survey schizophrenia
      and depression as examples of mental diseases and AD and PD as neurodegenerative
      diseases. We will review brain effects of estrogens, steroids possibly acting as
      pro-drugs of estrogens such as testosterone and dehydroepiandrosterone (DHEA) and
      present novel findings with SERMs. Drugs with estrogen activity in the brain may
      have therapeutic potential either by modulating brain neurotransmitter
      transmission or through neuroprotective activity.

PMID- 10903394
TI  - Looking back at Cannabis research.
AB  - Research leading to the isolation of the plant cannabinoids during the 1960 s and
      to the endogenous cannabinoids, during the 1990 s is described. Investigations on
      two non-psychotropic, synthetic cannabinoids, HU-211, a neuroprotective agent and
      HU-308, a specific CB2 agonist are presented.

PMID- 10903395
TI  - The search for selective ligands for the CB2 receptor.
AB  - Following the identification of the CB2 receptor several groups explored the
      development of selective ligands for this receptor which occurs principally in
      the periphery. This led to the discovery that two cannabimimetic indoles, 1-(2, 3
      dichlorobenzoyl)-2-methyl-3-(2-[1-morpholino]ethyl)-5-methoxyind ole (L768242)
      and 2-methyl-1-propyl-3-(1-naphthoyl)indole (JWH-015) have high affinity for the
      CB2 receptor with low affinity for the CB1 receptor. Shortly thereafter two 1
      methoxy-delta8-THC analogues, 1-methoxy-delta8-THC-DMH (L759633) and 1-methoxy
      delta9(11)-THC-DMH (L759656), were also found to have high affinity for the CB2
      receptor and very little affinity for the CB1 receptor. Almost simultaneously two
      1-deoxy-delta8-THC analogues, 1-deoxy-11-hydroxy-delta8-THC-DMH (JWH-051) and 1
      deoxy-delta8-THC-DMH (JWH-057) were reported to have high affinity for the CB1
      receptor, but even greater affinity for the CB2 receptor. These discoveries gave
      rise to a concerted effort by Huffman and co-workers to explore the structure
      activity relationships (SAR) at CB2 of cannabimimetic indoles and 1-deoxy-delta8
      THC analogues. These efforts have resulted in the synthesis and pharmacological
      evaluation of a number of derivatives of 3-(1-naphthoyl)indoles and 1-deoxy
      delta8-THC analogues with various side chains. This review will describe the
      current status of the results of these studies and discuss the SAR for both these
      classes of ligands.

PMID- 10903396
TI  - Ajulemic acid (CT3): a potent analog of the acid metabolites of THC.
AB  - The acid metabolites of THC were discovered almost 30 years ago and were later
      shown to posses modest analgesic and anti-inflammatory activity in a variety of
      models. Ajulemic acid (CT3) is a more potent analog of THC-11-oic acid in which a
      dimethylheptyl side chain is substituted for the pentyl side chain of the
      naturally occurring metabolite. It produces analgesia in the mouse hot plate, the
      PPQ writhing, the formalin and the tail clip assays. In the latter, it was
      equipotent to morphine; however, it showed a much greater duration of action. In
      the paw edema, subcutaneous air pouch and rat adjuvant-induced arthritis models
      of inflammation; it showed significant therapeutic activity at a dose of 0.2
      mg/kg p.o. In the arthritis model it greatly reduced permanent damage to joints
      when compared to an indomethacin control as evidenced by an improved joint score
      over vehicle controls and by histopathological examination. In contrast to the
      NSAIDs, it was totally nonulcerogenic at therapeutically relevant doses.
      Moreover, it does not depress respiration, exhibit dependence, induce body weight
      loss or cause mutagenesis. It shows none of the typical actions in models of the
      psychotropic actions of cannabinoids suggesting that a good separation of
      desirable from undesirable effects was achieved. Studies on its mechanism of
      action are currently underway. The data thus far suggest the existence of a novel
      receptor for ajulemic acid with possible downstream effects on eicosanoid
      production, cytokine synthesis and metalloprotease activity. There is also
      circumstantial evidence for a putative endogenous ajulemic acid, namely,
      arachidonylglycine.

PMID- 10903397
TI  - Nonpsychotropic synthetic cannabinoids.
AB  - Unlike natural cannabinoids which belong to the 6aR - trans series, the synthetic
      dexanabinol (HU-211), a 6aS-trans enantiomer, does not have affinity toward
      cannabinoid receptors and is devoid of cannabimimetic activity. On the other
      hand, dexanabinol demonstrated significant neuroprotective properties which
      prompted its development as a therapeutic agent. We now present the extension of
      a series of 6aS-trans cannabinoids with novel derivatives, including water
      soluble derivatives and congeners of dexanabinol.

PMID- 10903398
TI  - Endocannabinoids: new targets for drug development.
AB  - The possible therapeutic use of marijuana s active principles, the cannabinoids,
      is currently being debated. It is now known that these substances exert several
      of their pharmacological actions by activating specific cell membrane receptors,
      the CB1 and CB2 cannabinoid receptor subtypes. This knowledge led to the design
      of synthetic cannabinoid agonists and antagonists with high therapeutic
      potential. The recent discovery of the endocannabinoids, i.e. endogenous
      metabolites capable of activating the cannabinoid receptors, and the
      understanding of the molecular mechanisms leading to their biosynthesis and
      inactivation, opened a new era in research on the pharmaceutical applications of
      cannabinoids. Ongoing studies on the pathological and physiological conditions
      regulating the tissue levels of endocannabinoids, and on the pharmacological
      activity of these compounds and their derivatives, may provide a lead for the
      development of new drugs for the treatment of nervous and immune disorders,
      cardiovascular diseases, pain, inflammation and cancer. These studies are
      reviewed in this article with special emphasis on the chemical features that
      determine the interaction of endocannabinoids with the proteins mediating their
      activity and degradation.

PMID- 10903400
TI  - Radioimmunotherapy of cancer: using monoclonal antibodies to target radiotherapy.
AB  - After years of pre-clinical and clinical testing monoclonal antibodies (mAbs)
      finally offer new therapeutic choices for patients with haematological and solid
      malignancies both as unconjugated antibody and as vectors to target radionuclides
      in radioimmunotherapy (RIT). In recent years some of the most exciting clinical
      data have come from the use of RIT in the treatment of lymphoma and
      haematological malignancies and it would now appear highly likely that RIT will
      play a major role in the treatment strategies for these diseases. For the solid
      tumours there has also been considerable progress with RIT and mAbs have become a
      component of treatment protocols for breast cancer. This review highlights the
      important recent clinical progress that has been made with clinical RIT and
      provides some new insights into the important mechanisms of action of RIT in
      haematological malignancies.

PMID- 10903399
TI  - Natural and synthetic endocannabinoids and their structure-activity
      relationships.
AB  - During the past several years, cannabinoid biology has witnessed marked advances
      that has propelled it to the forefront of biomedical research. These new
      developments have also provided an opportunity to examine the physiological and
      biochemical events underlying the use and abuse of cannabis as well as
      elucidating the biological role of the endogenous cannabinoid ligands
      (endocannabinoids). The biological targets for endocannabinoids include the
      cannabinoid receptors (CB1 and CB2), the enzyme anandamide amidohydrolase (AAH),
      and the carrier protein referred to as the anandamide transporter (ANT). The
      identification of arachidonylethanolamide (anandamide, AEA) as an endogenous
      cannabinoid has been an important development in cannabinoid research which has
      led to the identification of two proteins associated with cannabinoid physiology
      in addition to the CB1 and CB2 receptors. These proteins are anandamide
      amidohydrolase (AAH), an enzyme responsible for the hydrolytic breakdown of
      anandamide and the anandamide transporter (ANT), a carrier protein involved in
      the transport of anandamide across the cell membrane. Evidence obtained so far
      suggests that these two proteins, in combination, are responsible for the
      termination of the biological actions of anandamide. Also, the discovery of
      anandamide has revealed a novel class of more selective agents possessing
      somewhat different pharmacological properties than the cannabinoids. A number of
      such analogs have now been reported many of which possess markedly improved
      cannabinoid receptor affinities and metabolic stabilities compared to those of
      the parent ligand. Generally, anandamide and all known analogs exhibit
      significant selectivities with high affinities for the CB1 receptor and modest to
      very low affinity for the CB2 receptor. In a relatively short period of time,
      pharmacological and biochemical studies have confirmed initial speculations that
      anandamide is either a neuromodulator or neurotransmitter and has significantly
      advanced our understanding of cannabinoid biochemistry. This summary seeks to
      define the pharmacology of endocannabinoids and to focus on the structure
      activity relationships (SAR) of anandamide for the CB1 cannabinoid receptor.

PMID- 10903401
TI  - Applications of gene transfer to targeted radiotherapy.
AB  - For targeted radionuclide therapy to succeed as a single modality treatment,
      schemes must be devised which will enable the deposition in malignant cells of
      sterilising doses of radiation. Until such methods have been perfected, it is
      necessary to combine targeted radiotherapy in a rational manner with conventional
      anti-cancer treatments. Several means of delivery of therapeutic radionuclides
      are being evaluated but none of these yet appears to be as powerful as the
      simplest and most effective example, viz: sodium [131I]iodide treatment of
      disseminated thyroid carcinoma. The radiopharmaceutical [131I]meta
      iodobenzylguanidine ([131I]MIBG) is an effective single agent for the treatment
      of neuroblastoma. However, uptake of the drug in malignant sites is
      heterogeneous, suggesting that this therapy alone is unlikely to cure disease. A
      growing body of experimental evidence indicates exciting possibilities for the
      integration of gene transfer with radionuclide targeting. This review covers
      aspects of the combination of gene manipulation and targeted radiotherapy,
      emphasising the potential of gene transfer to facilitate tumour targeting with
      low molecular weight radiopharmaceuticals.

PMID- 10903402
TI  - Astatine-211-labeled radiotherapeutics: an emerging approach to targeted alpha
      particle radiotherapy.
AB  - Targeted radiotherapy or endoradiotherapy is an appealing approach to cancer
      treatment because of the potential for delivering curative doses of radiation to
      tumor while sparing normal tissues. Radionuclides that decay by the emission of
      alpha-particles such as the heavy halogen astatine-211 (211At) offer the exciting
      prospect of combining cell-specific molecular targets with radiation having a
      range in tissue of only a few cell diameters. Herein, the radiobiological
      advantages of alpha-particle targeted radiotherapy will be reviewed, and the
      rationale for using 211At for this purpose will be described. The chemistry of
      astatine is similar to that of iodine; however, there are important differences
      which make the synthesis and evaluation of 211At-labeled compounds more
      challenging. Perhaps the most successful approach that has been developed
      involves the astatodemetallation of tin, silicon or mercury precursors. Astatine
      211 labeled agents that have been investigated for targeted radiotherapy include
      [211At]astatide, 211At- labeled particulates, 211At-labeled naphthoquinone
      derivatives, 211At-labeled methylene blue, 211At-labeled DNA precursors, meta
      [211At]astatobenzylguanidine, 211At-labeled biotin conjugates, 211At-labeled
      bisphosphonates, and 211At-labeled antibodies and antibody fragments. The status
      of these 211At-labeled compounds will be discussed in terms of their labeling
      chemistry, cytotoxicity in cell culture, as well as their tissue distribution and
      therapeutic efficacy in animal models of human cancers. Finally, an update on the
      status of the first clinical trial with an 211At-labeled targeted therapeutic,
      211At-labeled chimeric anti-tenascin antibody 81C6, will be provided.

PMID- 10903403
TI  - Synthesis of Auger electron-emitting radiopharmaceuticals.
AB  - Targeted radiotherapy using Auger electron-emitting pharmaceuticals offers both
      advantages and challenges compared to alternative alpha - or beta -emitting
      agents. The low energy Auger electrons deposit their energy within the target
      cell thereby minimizing collateral damage. To achieve this effect, however, the
      radiopharmaceutical must incorporate the appropriate radionuclide, be efficiently
      synthesized, and once administered, be distributed selectively to its biological
      target. This review covers the synthesis of agents which have prepared over the
      past decade either as Auger electron-emitting radiopharmaceuticals or which have
      the potential as such. While not an exhaustive review, the major classes of
      agents, such as hormone receptor ligands, nucleoside analogs and intercalating
      agents are described.

PMID- 10903404
TI  - Dosimetry and microdosimetry of targeted radiotherapy.
AB  - Dosimetry in targeted radiotherapy (TR) uses different calculation methods, whose
      degree of refinement is closely conditioned by the particular objective sought.
      It is more generally performed to establish a correlation between the quantity of
      radiation delivered to a target and the biological damage observed or that can be
      reliably predicted. It can thus be used to optimise treatments and allow
      comparison of different therapeutic approaches, as well as to study the basic
      methods of irradiation of biological matter. Two broad types of investigations
      can be found in the literature: microdosimetric ones (stochastic approaches used
      to study energy deposits) and macrodosimetric ones (non-stochastic or
      deterministic approaches). The mathematical formalism is consistent between these
      two types, and the calculation methods currently used are often similar. This
      review presents different approaches to the dosimetry of radionuclides used in
      TR. The introduction defines the general problem, the role of dosimetry in TR and
      the specific problems raised by targeting (non-uniformity of source
      distributions). The first part considers the types of calculation methods found
      in TR in relation to the basic quantities used to represent stochastic energy
      deposit on a cellular scale. In particular, it compares the formalism and the
      methods used in microdosimetric or conventional macrodosimetric approches.
      Although microdosimetry, or even track structure calculations, can provide the
      basic elements for modelling the absorbed dose process, a simplified dosimetric
      approach may be adequate to describe the phenomena observed. The scheme proposed
      by the MIRD committee relates to such an approach and is presented together with
      other methods allowing the calculation of the mean dose delivered (analytic
      methods, dose point kernels, Monte-Carlo, etc.). The second part shows the
      application range for the various methods, providing selected examples of
      dosimetric approaches in TR on different scales, from the organ (or tissues) to
      the cell or even DNA, and a brief presentation of bone marrow dosimetry.

PMID- 10903405
TI  - The imbalanced brain: from normal behavior to schizophrenia.
AB  - An outstanding problem in psychiatry concerns how to link discoveries about the
      pharmacological, neurophysiological, and neuroanatomical substrates of mental
      disorders to the abnormal behaviors that they control. A related problem concerns
      how to understand abnormal behaviors on a continuum with normal behaviors. During
      the past few decades, neural models have been developed of how normal cognitive
      and emotional processes learn from the environment, focus attention and act upon
      motivationally important events, and cope with unexpected events. When arousal or
      volitional signals in these models are suitably altered, they give rise to
      symptoms that strikingly resemble negative and positive symptoms of
      schizophrenia, including flat affect, impoverishment of will, attentional
      problems, loss of a theory of mind, thought derailment, hallucinations, and
      delusions. This article models how emotional centers of the brain, such as the
      amygdala, interact with sensory and prefrontal cortices (notably ventral, or
      orbital, prefrontal cortex) to generate affective states, attend to
      motivationally salient sensory events, and elicit motivated behaviors. Closing
      this feedback loop between cognitive and emotional centers is predicted to
      generate a cognitive-emotional resonance that can support conscious awareness.
      When such emotional centers become depressed, negative symptoms of schizophrenia
      emerge in the model. Such emotional centers are modeled as opponent affective
      processes, such as fear and relief, whose response amplitude and sensitivity are
      calibrated by an arousal level and chemical transmitters that slowly inactivate,
      or habituate, in an activity-dependent way. These opponent processes exhibit an
      Inverted-U, whereby behavior becomes depressed if the arousal level is chosen too
      large or too small. The negative symptoms are owing to the way in which the
      depressed opponent process interacts with other circuits throughout the brain.

PMID- 10903406
TI  - Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal
      cortex and basal ganglia during working memory performance.
AB  - BACKGROUND: Working memory (WM) deficits in schizophrenia have been associated
      with dorsolateral prefrontal cortex (DLPFC) dysfunction in neuroimaging studies.
      We previously found increased DLPFC activation in schizophrenic versus normal
      subjects during WM performance (Manoach et al 1999b). We now have investigated
      whether schizophrenic subjects recruit different brain regions, particularly the
      basal ganglia and thalamus, components of frontostriatal circuitry thought to
      mediate WM. METHODS: We examined regional brain activation in nine normal and
      nine schizophrenic subjects during WM performance using functional magnetic
      resonance imaging. Subjects performed a modified version of the Sternberg Item
      Recognition Paradigm that included a monetary reward for correct responses. We
      compared high and low WM load conditions to each other and to a non-WM baseline
      condition. We examined activation in both individual subjects and averaged group
      data. RESULTS: Relative to normal subjects, schizophrenic subjects exhibited
      deficient WM performance, at least an equal magnitude of right DLPFC activation,
      significantly greater left DLPFC activation, and increased spatial heterogeneity
      of DLPFC activation. Furthermore, only the schizophrenic group activated the
      basal ganglia and thalamus, even when matched for task performance with the
      normal group. CONCLUSIONS: Aberrant WM performance and brain activation in
      schizophrenia may reflect dysfunction of frontostriatal circuitry that subserves
      WM. Future studies will elucidate the contribution of the anatomical components
      of this circuitry to WM deficits.

PMID- 10903407
TI  - Regional frontal abnormalities in schizophrenia: a quantitative gray matter
      volume and cortical surface size study.
AB  - BACKGROUND: Previous structural studies of the frontal lobe in schizophrenia have
      had somewhat inconsistent results, but most of them have measured the frontal
      lobe as a single brain structure. To investigate more specific abnormalities in
      frontal subregions, we measured gray matter volume and cortical surface size in
      10 subregions in drug-naive patients during the early stages of the illness.
      METHODS: Magnetic resonance imaging was used to measure frontal subregions in 34
      healthy male volunteers, and 26 male, drug-naive schizophrenia patients at early
      stages of the illness. Frontal subregions were manually traced using our locally
      developed parcellation method. RESULTS: Patients with schizophrenia had a
      significant deficit in cortical surface size in the right straight gyrus and left
      orbitofrontal cortex. No differences were found in gray matter volumes.
      CONCLUSIONS: Frontal structural abnormalities found in drug-naive schizophrenic
      patients appear to be subtle and circumscribed to ventral portions. Anomalies in
      the cortical surface size suggest neurodevelopmental abnormalities might occur
      during the early stages of the gyrogenesis. Further investigations are needed to
      explore the implications of paralimbic ventral frontal regions (i.e., straight
      gyrus and orbitofrontal cortex) in the pathophysiology of schizophrenia.

PMID- 10903408
TI  - Neuropsychologic functioning among the nonpsychotic relatives of schizophrenic
      patients: the effect of genetic loading.
AB  - BACKGROUND: We previously reported that the nonpsychotic relatives of
      schizophrenic patients exhibited disturbances in executive functioning, verbal
      and visual memory, auditory attention, mental control, and verbal ability. In a 4
      year follow-up, we showed that the discriminating power of most of these tests
      was stable over time. METHODS: In this report we compare 41 nonpsychotic persons
      who have only one schizophrenic first-degree relative (simplex families) with 36
      nonpsychotic persons who have two schizophrenic first-degree relatives (multiplex
      families). Our goal was to test a hypothesis that neuropsychologic deficits would
      be worse among the latter. RESULTS: Relatives from multiplex families differed
      significantly from controls on estimated intelligence, immediate and delayed
      logical memories, and immediate visual reproductions. In contrast, in comparisons
      with controls, relatives from simplex families only differed on immediate logical
      memories. Comparisons between relatives from multiplex and simplex families
      showed that the former group had significantly worse scores for estimated
      intelligence, immediate and delayed logical memories, and immediate visual
      reproductions. We also found group x gender interactions: the worse performance
      of the multiplex group was seen for females. CONCLUSIONS: These results are
      consistent with the idea that neuropsychologic deficits in relatives of
      schizophrenic patients reflect their degree of genetic predisposition to
      schizophrenia. They also suggest hypotheses about gender differences in the
      familial transmission of the disorder.

PMID- 10903409
TI  - Emotion recognition deficit in schizophrenia: association with symptomatology and
      cognition.
AB  - BACKGROUND: Previous investigations have found impaired recognition of facial
      affect in schizophrenia. Controversy exists as to whether this impairment
      represents a specific emotion recognition deficit when compared with other face
      recognition control tasks. Regardless of whether the emotion processing deficit
      is differential, it may uniquely influence other manifestations of schizophrenia.
      We compared patients and healthy control subjects on computerized tasks of
      emotion and age recognition. Performances on emotion and age recognition tasks
      were correlated with cognitive functioning and with symptomatology. METHODS:
      Thirty-five patients with schizophrenia and 45 healthy people underwent
      computerized testing for emotion and age recognition. Participants were assessed
      neuropsychologically, and patients were rated for positive and negative symptoms.
      RESULTS: The patients with schizophrenia performed worse than control subjects on
      emotion and age recognition without differential deficit. In both groups, we
      found higher error rates for identification of emotion in female faces and for
      identification of sad versus happy faces. In schizophrenic patients, emotion but
      not age recognition correlated with severity of negative and positive symptoms.
      In healthy control subjects, neither task correlated with cognitive functions. In
      schizophrenic patients, emotion but not age recognition correlated with
      attention, verbal and spatial memory, and language abilities. CONCLUSIONS: This
      study did not reveal a specific deficit for emotion recognition in schizophrenia;
      however, our findings lend support to the concept that emotion recognition is
      uniquely associated in schizophrenia with core symptomatology and cognitive
      domains.

PMID- 10903410
TI  - Age and neuropsychologic function in schizophrenia: a decline in executive
      abilities beyond that observed in healthy volunteers.
AB  - BACKGROUND: Kraepelin originally conceptualized schizophrenia as a degenerative
      brain disorder. It remains unclear whether the illness is characterized by a
      static encephalopathy or a deterioration of brain function, or periods of each
      condition. Assessments of cognitive function, as measured by neuropsychologic
      assessment, can provide additional insight into this question. Few studies of
      patients with schizophrenia have investigated the effect of aging on executive
      functions, in an extensive neuropsychologic battery across a wide age range,
      compared to healthy volunteers. METHODS: We examined the interaction of aging and
      neuropsychologic function in schizophrenia through a cross-sectional study in
      patients (n = 87) and healthy control subjects (n = 94). Subjects were divided
      into three age groups (20-35, 36-49, and 50-75), and performance on an extensive
      neuropsychologic battery was evaluated. RESULTS: Compared to control subjects,
      patients with schizophrenia demonstrated similar age-related declines across most
      neuropsychologic functions, with the exception of abstraction ability, in which
      significant evidence of a more accelerated decline was observed. CONCLUSIONS:
      These results are consistent with previous reports indicating similar age effects
      on most aspects of cognition in patients with schizophrenia and healthy adults,
      but they support the hypothesis that a degenerative process may result in a more
      accelerated decline of some executive functions in older age in schizophrenia.

PMID- 10903411
TI  - An MRI study of temporal lobe structures in men with bipolar disorder or
      schizophrenia.
AB  - BACKGROUND: Hippocampal atrophy has been described in postmortem and magnetic
      resonance imaging studies of schizophrenia. The specificity of this finding to
      schizophrenia remains to be determined. The neuropathology of bipolar disorder is
      understudied, and temporal lobe structures have only recently been evaluated.
      METHODS: Twenty-four bipolar, 20 schizophrenic, and 18 normal comparison subjects
      were evaluated using magnetic resonance brain imaging. Image data were acquired
      using a three-dimensional spoiled GRASS sequence, and brain images were
      reformatted in three planes. Temporal lobe structures including the amygdala,
      hippocampus, parahippocampus, and total temporal lobe were measured to obtain
      volumes for each structure in the three subject groups. Severity of symptoms in
      both patient groups was assessed at the time the magnetic resonance images were
      obtained. RESULTS: Hippocampal volumes were significantly smaller in the
      schizophrenic group than in both bipolar and normal comparison subjects. Further,
      amygdala volumes were significantly larger in the bipolar group than in both
      schizophrenic and normal comparison subjects. CONCLUSIONS: The results suggest
      differences in affected limbic structures in patients with schizophrenia and
      bipolar disorder. These specific neuroanatomic abnormalities may shed light on
      the underlying pathophysiology and presentation of the two disorders.

PMID- 10903412
TI  - Long-term adaptive life functioning in relation to initiation of treatment with
      antipsychotics over the lifetime trajectory of schizophrenia.
AB  - BACKGROUND: There is evidence that the stage of illness at which antipsychotic
      treatment is initiated in schizophrenia may have consequences for its subsequent
      course. How this might relate to impaired adaptive life functioning in the long
      term is poorly understood. METHODS: Thirty-eight inpatients, many of whom had
      been admitted in the preneuroleptic era, were assessed using the Social-Adaptive
      Functioning Evaluation (SAFE); constituent clinical and medication phases of the
      lifetime trajectory of their illnesses were then analyzed to identify predictors
      of SAFE score using multiple regression modeling. RESULTS: The primary,
      independent predictor of SAFE score was duration of initially unmedicated
      psychosis, which accounted for 22% of variance (p<.001) therein. Conversely,
      duration of subsequently treated illness, although decades longer, failed to
      predict SAFE score. CONCLUSIONS: These findings are consistent with some form of
      "progressive" process, particularly over the first several years following the
      emergence of psychosis, which is associated with accrual of deficits in adaptive
      life functioning.

PMID- 10903413
TI  - H(2) antagonist nizatidine may control olanzapine-associated weight gain in
      schizophrenic patients.
AB  - BACKGROUND: Olanzapine is temporally associated, in a number of patients with
      schizophrenia, with weight gain. H(2) antagonists, like nizatidine, have been
      shown to control appetite in overweight patients. METHODS: A patient with
      olanzapine temporally associated weight gain was treated with nizatidine as "add
      on" therapy. RESULTS: Nizatidine treatment was associated with good control and
      subsequent reduction of weight after 4 to 5 weeks of therapy in a patient with
      repetitive episodes of weight gain during olanzapine treatment. Olanzapine was
      otherwise well tolerated and effective in controlling psychopathology.
      CONCLUSIONS: H(2) antagonist treatment with olanzapine may be a valid medical
      strategy in preventing and/or reducing weight gain in patients with
      schizophrenia. Controlled studies are recommended to confirm this observation.

PMID- 10903415
TI  - Basal and drug-induced antioxidant enzyme activities correlate with age-dependent
      doxorubicin oxidative toxicity.
AB  - Doxorubicin continues to be one of the most widely used anticancer agents in the
      clinic despite its dose-limiting side-effects. Many of doxorubicin's dose
      limiting toxicities occur due to its generation of toxic oxygen species,
      resulting in oxidative stress. Some clinical observations have suggested that
      doxorubicin may have greater toxicity in older patients. The studies presented
      here compare basal and doxorubicin-induced antioxidant enzyme activities in
      brain, heart, kidney and liver tissues of Fisher 344 rats of different ages to
      determine whether differences in these enzymes can account for the age-dependent
      differences observed in doxorubicin-induced toxicity. Three groups of animals
      were tested, young animals (2-months-old), adult animals (10-months-old) and old
      animals (18-months-old). The results of these studies show that in general young
      and adult animals have similar levels of antioxidant enzyme activity while the
      older animals have less. Only in the young animals is antioxidant enzyme activity
      significantly increased following doxorubicin treatment suggesting that enzyme
      induction occurs only in the young group of animals. Lipid peroxidation is shown
      to have the greatest increase in the old animals following doxorubicin treatment
      while the young animals have the smallest increase. The results from these
      studies suggest that there is an increase in doxorubicin-induced oxidative damage
      with age and that these differences may be due to basal and drug-induced
      differences in tissue antioxidant enzyme activities.

PMID- 10903416
TI  - Role of glucose utilization in the restoration of hypophysectomy-induced hepatic
      cytochrome P450 2E1 by growth hormone in rats.
AB  - Growth hormone and insulin are the primary determinants for cytochrome P450 2E1
      (CYP2E1) expression. The role of glucose on the induction of CYP2E1 by
      hypophysectomy and on the restorative effect by growth hormone was investigated
      in the rat liver. Western and Northern blot analyses revealed that hypophysectomy
      induced CYP2E1 by 5-fold at 1-4 weeks, relative to control, with a concomitant
      increase in CYP2E1 mRNA. Hypophysectomized rats (HXR) showed a 20% reduction in
      the plasma glucose level. Hypophysectomy-induced increase in the CYP2E1 mRNA was
      completely abolished by glucose feeding in drinking water (10%) for 7 days.
      Treatment of HXR with hGH (2 I.U./kg, twice a day, for 7 days) inhibited the
      increases in CYP2E1 protein and mRNA levels with restoration of the plasma
      glucose level. In contrast to the effect of human growth hormone (hGH) on CYP2E1
      in HXR with free access to foods, CYP2E1 expression failed to be restored by hGH
      in starving HXR. However, glucose feeding of starving HXR abolished the induction
      of CYP2E1. Effects of hypophysectomy and hGH treatment were studied in
      streptozotocin-induced diabetic rats. Insulin, but not hGH, prevented an increase
      in CYP2E1 mRNA in diabetic rats. The hepatic CYP2E1 induction in
      hypophysectomized diabetic rats was inhibited by hGH treatment, indicating that
      the hGH effect on CYP2E1 expression did not involve insulin production. These
      results provide evidence that the induction of hepatic CYP2E1 by hypophysectomy
      may result from reduced glucose utilization, and that the effect of hGH on CYP2E1
      expression may be mediated with enhanced glucose utilization, but not with
      insulin production.

PMID- 10903417
TI  - In vitro DNA and dGMP adducts formation caused by ochratoxin A.
AB  - Ochratoxin A (OTA), a nephrotoxic and nephrocarcinogenic mycotoxin, leads to the
      formation of DNA adducts after administration to animals. This could be due to an
      epigenetic effect. In vitro assays can exclude an indirect effect, where the
      xenobiotic can generate, in vivo, endogenous reactive compounds which give
      adducts on DNA. Microsomes prepared from mice or rabbit kidney and liver, used as
      metabolic activators, were incubated in the presence of commercial salmon testes
      DNA and OTA, with NADPH or arachidonic acid used as cofactors. Upto 126 DNA
      adducts for 10(9) nucleotides were detected using the 32P postlabeling method
      after incubation with the mouse kidney system. Similar results were obtained with
      rabbit kidney microsomes. Using liver microsomes, the number of DNA adducts
      detected was much lower. When NADPH was used as a cosubstrate (to explore the
      cytochrome P450 metabolic pathways), with mice kidney microsomes, the adduct
      level was only 44% of the one obtained with arachidonic acid. These results lend
      support to the hypothesis of the preferential activation of OTA by the peroxidase
      activity of prostaglandin synthases and/or lipoxygenases to direct genotoxic
      metabolites, and are in agreement with the previously obtained results after in
      vivo treatment of mice. In order to identify the nucleotides of DNA modified by
      the OTA metabolites, dAMP, dGMP, dTMP and dCMP were used as substrates under the
      same conditions as with DNA. The adducts were found only on dGMP. The total
      adduct level was of 344 adducts per 10(9) nucleotides with the appearance of
      three major adducts in the presence of arachidonic acid. With NADPH, 271 adducts
      were obtained per 10(9) nucleotides, with again three major adducts, but only two
      of them were similar to two adducts obtained in the presence of arachidonic acid.
      Desferal (desferrioxamine B methanesulphonate), at a 50 microM concentration, did
      not reduce the adduct level. Adducts were also obtained when polydG, polydC and
      dG-p-dG were used as alternative substrates, whereas no adducts were obtained
      with polydA, polydT and polydC. The major adduct obtained after incubation of DNA
      with OTA, comigrated with the major adduct obtained with dGMP, in two
      chromatographic solvents. These results show that OTA is metabolized to genotoxic
      metabolite(s) which interact with the guanine residues of DNA.

PMID- 10903418
TI  - Inhibition of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin
      ornithine decarboxylase and protein kinase C by polyphenolics from grapes.
AB  - Ornithine decarboxylase is the rate-limiting enzyme in the biosynthesis of
      polyamines, which are believed to play an essential role in diverse biological
      processes including cell proliferation and differentiation. We have previously
      reported [J. Bomser, K. Singletary, M. Wallig, M. Smith, Inhibition of TPA
      induced tumor promotion in CD-1 mouse epidermis by a polyphenolic fraction from
      grape seeds, Cancer Letters 135 (1999) 151-157] that pre-application of a grape
      polyphenolic fraction (GPF) to mouse skin epidermis inhibits 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC)
      activity, as well as 7, 12-dimethylbenz[a]anthracene (DMBA)-initiated, TPA
      promoted mouse skin tumorigenesis. The present studies were designed to further
      characterize the effect of time and dose of application of GPF on TPA-induced ODC
      activity and protein expression, and on protein kinase C activity in mouse skin
      epidermis. In addition, the effect of GPF on ODC kinetics in vitro was examined.
      Application of 5, 10, and 20 mg of GPF 20 min prior to treatment with TPA
      resulted in a significant decrease in epidermal ODC activity of 54, 53, 90%,
      respectively, compared with controls. Yet, ODC protein levels (Western blot) in
      the 10 and 20 mg GPF groups were significantly increased by 1.8 and 1.9-fold,
      respectively, compared with controls. A similar response was observed with the
      ODC inhibitor 2-difluoromethylornithine (DFMO), which served as a positive
      control. Application of grape polyphenolics (20 mg) at 60 and 30 min prior to
      treatment with TPA inhibited ODC activity by 62 and 68%, respectively, compared
      with controls (P<0.05). In contrast, application of grape polyphenolics (20 mg)
      at 60, 120 and 240 min after treatment with TPA resulted in no significant
      changes in ODC activity. A similar increase in epidermal ODC protein was observed
      in these GPF-treated animals, similar to that observed when GPF application
      preceded TPA. When applied to mouse skin prior to TPA, GPF was associated with a
      decrease in subsequent PKC activity compared with controls at 10 and 30 min
      following TPA treatment. The GPF-associated decrease in PKC activity preceded the
      decrease in ODC activity. In a separate in vitro study, kinetic analyses
      indicated that GPF is a competitive inhibitor of ODC activity. Collectively these
      data suggest that the grape polyphenolic fraction is effective as an inhibitor of
      ODC activity when applied before TPA, and that the magnitude of inhibition is
      independent of epidermal ODC protein content. In addition, GPF is a competitive
      inhibitor of ODC activity in vitro. The decrease in TPA-induced ODC activity due
      to GPF treatment is preceded by an inhibition of TPA-induced PKC activity. Thus,
      the polyphenolic fraction from grapes warrants further examination as a skin
      cancer chemopreventive agent that interferes with cellular events associated with
      TPA promotion.

PMID- 10903419
TI  - Comparative QSAR evidence for a free-radical mechanism of phenol-induced
      toxicity.
AB  - Phenol and 14 substituted-phenols were tested for their ability to impair
      epithelial cell membrane integrity in WB rat liver cells as determined by an
      increase in lactate dehydrogenase release. Two quantitative structure-activity
      relationship (QSAR) regression equations were developed which showed that
      separate mechanisms of phenolic cytotoxicity are important - nonspecific toxicity
      due to hydrophobicity and formation of phenoxyl radicals. The equations most
      predictive of phenol toxicity are denoted as log1/C=-0. 98sigma(+)+0.77logP+0.23
      or log1/C=-0.11BDE+0.76logP+0.21, respectively, where C is the minimum
      concentration of substituted-phenol required for a toxic response. P is the
      octanol-water partition coefficient, sigma(+) is the electronic Hammett parameter
      and BDE is the OH homolytic bond dissociation energy. In the literature, phenol
      toxicity correlated to sigma(+) is rare, but there is strong evidence that
      phenols possessing electron-releasing groups may be converted to toxic phenoxyl
      radicals. A common feature in a variety of cells is generation of elevated
      amounts of reactive oxygen species (ROS) associated with a rapid growth rate. The
      slightly elevated cancer risk associated with the use of Premarin may be due to
      phenoxyl-type radicals derived from one or more of its components.

PMID- 10903420
TI  - Species difference in enantioselectivity for the oxidation of propranolol by
      cytochrome P450 2D enzymes.
AB  - We examined and compared enantioselectivity in the oxidation of propranolol (PL)
      by liver microsomes from humans and Japanese monkeys (Macaca fuscata). PL was
      oxidized at the naphthalene ring to 4-hydroxypropranolol, 5-hydroxypropranolol
      and side chain N-desisopropylpropranolol by human liver microsomes with
      enantioselectivity of [R(+)>S(-)] in PL oxidation rates at substrate
      concentrations of 10 microM and 1 mM. In contrast, reversed enantioselectivity
      [R(+)<S(-)] in PL 5-hydroxylation and N-desalkylation rates at the same substrate
      concentrations was observed in monkey liver microsomes, although the selectivity
      was the same for PL 4-hydroxylation between the two species. All oxidation
      reactions of the PL enantiomers in human liver microsomes showed biphasic
      kinetics, i.e. the reactions could be expressed as the summation of a low-K(m)
      phase and a high-K(m) phase. Inhibition studies using antibodies and
      characterization of CYP2D6 enzymes expressed in insect cells or human
      lymphoblastoid cells indicated that the enantioselectivity of PL oxidation,
      especially the ring 4- and 5-hydroxylations reflected the properties of CYP2D6 in
      human liver microsomes. In monkey liver microsomes, all of the oxidation
      reactions of S(-)-PL showed biphasic kinetics, whereas ring 4- and 5
      hydroxylations were monophasic and side chain N-desisopropylation was biphasic
      for R(+)-PL. Similarly, from the results of inhibition studies using antibodies
      and inhibitors of cytochrome P450 (P450), it appears that the reversed
      selectivity [R(+)<S(-)] of PL oxidation rates is catalyzed by CYP2D enzyme(s) in
      monkey liver at low substrate concentrations. These results indicate that
      different properties of P450s belonging to the 2D subfamily cause the reversed
      enantioselectivity between human and monkey liver microsomes.

PMID- 10903421
TI  - Evaluation of the effect of culture matrices on induction of CYP3A isoforms in
      cultured porcine hepatocytes.
AB  - Several bioartificial liver devices have been developed as temporary therapy for
      patients suffering from fulminant hepatic failure. Some of these devices contain
      porcine hepatocytes entrapped in collagen matrices. In order to improve the
      function of these BAL devices, there exists a need to optimize metabolic function
      of cultured hepatocytes. The goal of these investigations was to evaluate the
      effect of altering culture conditions on rifampin-mediated induction of CYP3A
      isoforms in cultured porcine hepatocytes. Midazolam metabolism was compared in
      porcine hepatocytes cultured in a monolayer configuration on collagen gels, in a
      sandwich configuration between collagen gels and a Matrigel overlay, and in
      spheroidal cultures. The effect of culture conditions was evaluated, by measuring
      CYP3A-mediated metabolism of midazolam and by immunoblotting to detect CYP3A
      proteins, in control cultures and in rifampin-treated cultures. Results obtained
      by normalizing the metabolism rate data to cell numbers (based on DNA content)
      present at the end of the culture experiment, showed that there was no difference
      between the different culture conditions tested. Our results suggest that
      culturing porcine hepatocytes as spheroids or in a sandwich configuration between
      collagen and Matrigel, offers no advantage in terms of CYP3A-mediated metabolic
      function on a per cell basis compared to culturing on collagen gels.

PMID- 10903422
TI  - Involvement of p27(kip1) and cyclin D3 in the regulation of cdk2 activity during
      skeletal muscle differentiation.
AB  - Terminal myogenic differentiation involves an irreversible transition from a
      proliferative state to a post-mitotic quiescent state. We showed here that in
      addition to the previously reported down regulation of G(1)-related cyclin
      associated kinase activities, this transition was also accompanied by an
      extensive reorganization of the cyclin-cdk complexes, including a dramatic shift
      of cdk2 from cyclin A to cyclin D3. Moreover, the inhibition of cdk activity also
      correlated with an increase in the expression of the p27(kip1) cdk inhibitor and
      in its association with the cyclin-cdk2 complexes. Since depletion of p27
      substantially reduced the cdk inhibitor activity present in differentiated muscle
      cells, we believe that the increase in p27 expression along with the
      reorganization of the cyclin-cdk2 complexes may play an important role in the
      inhibition of cdk2 activity during the differentiation process.

PMID- 10903423
TI  - Bone morphogenetic protein-2 induces cyclin kinase inhibitor p21 and
      hypophosphorylation of retinoblastoma protein in estradiol-treated MCF-7 human
      breast cancer cells.
AB  - The biologic effects and mechanisms by which bone morphogenetic proteins (BMPs)
      function in breast cancer cells are not well defined. A member of this family of
      growth and differentiation factors, BMP-2, inhibited both basal and estradiol
      induced growth of MCF-7 breast tumor cells in culture. Flow cytometric analysis
      showed that in the presence of BMP-2, 62% and 45% of estradiol-stimulated MCF-7
      cells progressed to S-phase at 24 h and 48 h, respectively. Estradiol mediates
      growth of human breast cancer cells by stimulating cyclins and cyclin-dependent
      kinases (CDKs). BMP-2 significantly increased the level of the cyclin kinase
      inhibitor, p21, which in turn associated with and inactivated cyclin D1. BMP-2
      inhibited estradiol-induced cyclin D1-associated kinase activity. Also estradiol
      induced CDK2 activity was inhibited by BMP-2. This inhibition of CDK activity
      resulted in hypophosphorylation of retinoblastoma protein thus keeping it in its
      active form. These data provide the first evidence by which BMP-2 inhibits
      estradiol-induced proliferation of human breast cancer cells.

PMID- 10903424
TI  - Association of CD44 with OTS-8 in tumor vascular endothelial cells.
AB  - Endothelial cells in solid tumors play an important role in tumor growth,
      invasion and metastasis through angiogenesis. We have recently cloned two tumor
      vascular antigens from isolated rat tumor vascular endothelial cells (TEC). One
      is CD44, a family of cell surface proteins implicated in adhesion interactions
      and tumor metastasis. The other is OTS-8, a marker for osteoblast into osteocyte
      transition and type I alveolar epithelial cells termed as E11 antigen and RTI40,
      respectively. To test for a possible interaction between the two antigens on
      endothelial cells in tumor angiogenesis, we examined in vivo association of CD44
      with OTS-8 using lysates of isolated rat TEC and COS-7 cells cotransfected with
      CD44 and OTS-8 expression plasmids. The association was detected by direct co
      immunoprecipitation of the two types of cells lysed with digitonin, whereas the
      detection was lost when lysed with Nonidet P-40. To confirm this association,
      intact COS-7 cells cotransfected were reacted with homobifunctional N
      hydroxysuccinimide ester crosslinking reagents. Immunoblot analysis showed a
      crosslinked CD44/OTS-8 protein complex of 120 kDa, suggesting the proximity of
      the two proteins. These findings provide evidence of a weak physical association
      between CD44 and OTS-8 in TEC, and suggest that OTS-8 may alter the mode of
      endothelial cell growth and/or migration induced by CD44 in tumor angiogenesis.

PMID- 10903425
TI  - Human satellite 3 (HS3) binding protein from the nuclear matrix: isolation and
      binding properties.
AB  - Satellite DNA (satDNA) is the main component of residual DNA in nuclear matrix
      (NM) preparations. Gel mobility shift assay (GMSA) revealed specific human
      satellite 3 (HS3) binding activity in NM extracts. An HS3 binding protein was
      purified using diethylaminoethyl (DEAE)-cellulose and preparative GMSA. The
      binding was specific, although other satDNA fragments compete to some extent for
      the binding. DNase I footprinting and methylation interference revealed multiple
      points of protection distributed throughout the HS3 fragment with periodicity of
      about 10 bp, mostly inside an AT island. Polyclonal antibodies (AB) were raised
      against HS3-protein complexes cut from the preparative GMSA gel. On immunoblots,
      AB recognise a protein, which is not lamin, with apparent molecular mass 70 kDa,
      the same as revealed by purification (p70). In in situ nuclear matrix
      preparations combined immunofluorescence (AB) and fluorescent in situ
      hybridisation (HS3) shows that HS3 and p70 areas correspond to each other. The
      localisation of this protein detected with AB in interphase nuclei coincides with
      the heterochromatic regions which surround nucleoli in correspondence with the
      known HS3 position in the nuclei.

PMID- 10903426
TI  - Reduced growth rate accompanied by aberrant epidermal growth factor signaling in
      drug resistant human breast cancer cells.
AB  - We examined transforming growth factor (TGF) alpha, epidermal growth factor (EGF)
      and EGF receptor (EGFR) expression and signaling in three drug resistant MCF-7
      human breast cancer sublines and asked whether these pathways contribute to the
      drug resistance phenotype. In the resistant sublines, upregulation of both
      TGFalpha and EGFR mRNA was observed. In an apparent contrast with upregulated
      growth factor and receptor gene expression, the drug resistant sublines displayed
      a reduced growth rate. Defects in the EGFR signaling pathway cascade were found
      in all examined drug resistant sublines, including altered EGF-induced Shc, Raf
      1, or mitogen-activated protein kinase phosphorylation. Induction of c-fos mRNA
      expression by EGF was impaired in the sublines compared to parental MCF-7 cells.
      In contrast, the induction of the stress-activated protein kinase activity was
      similar in both parental and drug resistant cells. Evaluating the link between
      the reduced growth rate and drug resistance, serum starvation experiments were
      performed. These studies demonstrated that a reduced proliferative activity
      resulted in a marked reduction in sensitivity to cytotoxic agents in the parental
      MCF-7 cells. We propose that the altered EGFR levels frequently observed in drug
      resistant breast cancer cells are associated with perturbations in the signaling
      pathway that mediate a reduced proliferative rate and thereby contribute to drug
      resistance.

PMID- 10903428
TI  - Parathyroid hormone-related peptide inhibits the expression of bone morphogenetic
      protein-4 mRNA through a cyclic AMP/protein kinase A pathway in mouse clonal
      chondrogenic EC cells, ATDC5.
AB  - The bone morphogenetic proteins (BMPs) play crucial roles in chondrogenic
      differentiation. Little is known, however, regarding the regulation of BMP gene
      expression. Here we examined the effect of parathyroid hormone-related peptide
      (PTHrP) (1-141), a full-length form of PTHrP molecules, on the expression of BMP
      4 mRNA in clonal mouse chondrogenic EC cells, ATDC5. In differentiated ATDC5
      cells, the expression of BMP-4 mRNA was inhibited by PTHrP (1-141), which
      stimulated cAMP accumulation and protein kinase A (PKA) activity in these cells.
      Dibutyryl cAMP, a permeable analog of cAMP, mimicked and H-89, a selective PKA
      inhibitor, blocked this effect of PTHrP (1-141). Moreover, actinomycin D
      attenuated the inhibition of BMP-4 mRNA expression by PTHrP (1-141). These
      results indicate that PTHrP (1-141) transcriptionally inhibits the expression of
      BMP-4 mRNA through a cAMP/PKA pathway in ATDC5 cells.

PMID- 10903427
TI  - Immobilised echistatin promotes platelet adhesion and protein tyrosine
      phosphorylation.
AB  - Echistatin, a 5000-Da disintegrin, is a strong competitive inhibitor of platelet
      alpha(IIb)beta(3) binding to fibrinogen. In addition to its antiplatelet
      activity, echistatin also exhibits activating properties by inducing a switch of
      alpha(IIb)beta(3) conformation towards an active state. However, soluble
      echistatin, which is a monomeric ligand, provides only receptor affinity
      modulation, but it is unable to activate integrin-dependent intracellular
      signals. Since proteins may exhibit a multivalent functionality as a result of
      their absorption to a substrate, in this study we evaluated whether immobilised
      echistatin is able to stimulate platelet adhesion and signalling. The
      immobilisation process led to an increase of echistatin affinity for integrin(s)
      expressed on resting platelets. Unlike the soluble form, immobilised echistatin
      bound at comparable extent either unstimulated or ADP-activated platelets.
      Furthermore, echistatin presented in this manner was effective in stimulating
      integrin-dependent protein tyrosine phosphorylation. Platelets adhering to
      immobilised echistatin showed a pattern of total tyrosine phosphorylated proteins
      resembling that of fibrinogen-attached platelets. In particular, solid-phase
      echistatin induced a strong phosphorylation of tyrosine kinases pp72(syk) and
      pp125(FAK). Inhibitors of platelet signalling, such as apyrase, prostaglandin
      E(1), cytochalasin D and bisindolylmaleimide, while not affecting platelet
      adhesion to immobilised echistatin, abolished pp125(FAK) phosphorylation. This
      suggests that signals activating protein kinase C function, dense granule
      secretion and cytoskeleton assembly might be involved in echistatin-induced
      pp125(FAK) phosphorylation.

PMID- 10903429
TI  - High glucose attenuates insulin-induced mitogen-activated protein kinase
      phosphatase-1 (MKP-1) expression in vascular smooth muscle cells.
AB  - The mechanisms for the effect of hyperglycemia on insulin-induced mitogenesis
      were investigated using rat vascular smooth muscle cells (VSMC). VSMC were
      preincubated in serum-free medium with low (5 mM) glucose (LG condition) or high
      (25 mM) glucose (HG condition), and examined for DNA synthesis using
      bromodeoxyuridine (BrdUrd) incorporation. Mitogen-activated protein kinase (MAPK)
      activity and MAPK phosphatase (MKP-1) protein expression were detected by Western
      blot analysis. Phosphatidylinositol 3-kinase (PI-3K) activity was detected by
      thin layer chromatography. Insulin induced a dose-dependent increase in BrdUrd
      incorporation (123.3+/-2.6% over basal level with 1 microM insulin) in the LG
      group and this effect was significantly enhanced (161.6+/-10.4% over basal level)
      in the HG group. In the LG group, MAPK activity was transient with a peak
      activation (137.4+/-11.2% over basal level) after 10 min exposure to 100 nM
      insulin. In the HG group, the MAPK activity was significantly potentiated (two
      fold compared to the LG group) and was sustained even after 60 min. Insulin also
      induced PI-3K activity and MKP-1 expression, both of which were blocked by the PI
      3K inhibitor wortmannin. In the HG group, insulin-induced PI-3K and MKP-1
      expression was almost abolished. In conclusion, high glucose enhances insulin
      induced mitogenesis associated with the potentiation of insulin-stimulated MAPK
      activity in VSMC. These effects of glucose might in part be due to the
      attenuation of MKP-1 expression through the blockage of the insulin-PI-3K signal
      pathway.

PMID- 10903430
TI  - Profilin I attached to the Golgi is required for the formation of constitutive
      transport vesicles at the trans-Golgi network.
AB  - Profilin I was identified, by mass spectrometric sequencing and immunoblotting,
      as a component of purified Golgi cisternae from HepG2 cells. Binding to the Golgi
      was verified by indirect immunofluorescence in MT-1 cells showing that a fraction
      of profilin I colocalizes with TGN38, a marker of the trans-Golgi network (TGN).
      Studying the formation of constitutive exocytic vesicles at the TGN in a cell
      free system demonstrated that cytosolic profilin I has no effect, while
      incubation of Golgi cisternae with a profilin I-specific antibody reduced vesicle
      formation by about 50%. Notably, the antibody displaces a fraction of the Golgi
      bound dynamin II indicating that profilin I may indirectly promote vesicle
      formation by supporting the binding of dynamin II to the Golgi membrane. The
      impact of dynamin II on vesicle formation is demonstrated by incubating the Golgi
      with the proline-rich domain of dynamin II which concomitantly displaces dynamin
      II and inhibits vesicle formation. The data provide evidence that profilin I
      attaches to the Golgi apparatus and is required for the formation of constitutive
      transport vesicles.

PMID- 10903431
TI  - Pyrimidinoceptors-mediated activation of Ca(2+)-dependent Cl(-) conductance in
      mouse endometrial epithelial cells.
AB  - Previous studies have demonstrated the activation of endometrial Cl(-) secretion
      through P(2Y2) (P(2U)) purinoceptors by extracellular ATP. The present study
      further explored the presence of pyrimidine-sensitive receptors in the primary
      cultured mouse endometrial epithelial cells using the short-circuit current
      (I(SC)) and whole-cell patch-clamp techniques. UDP induced a transient increase
      in I(SC) in a concentration-dependent manner (EC(50) approximately 8.84 microM).
      The UDP-induced I(SC) was abolished after pretreating the epithelia with a
      calcium chelator, 1, 2-bis-(2-aminophenoxy)-ethane-N,N,N'N'tetraacetic acid
      acetomethyl ester (BAPTA-AM), suggesting the dependence of the I(SC) on cytosolic
      free Ca(2+). The type of receptor involved was studied by cross-desensitization
      between ATP and UDP. ATP or UDP desensitized its subsequent I(SC) response.
      However, when ATP was added after UDP, or vice versa, a second I(SC) response was
      observed, indicating the activation of distinct receptors, possibly pyrimidine
      sensitive receptors in addition to P(2Y2) (P(2U)) receptors. Similar results were
      observed in the patch-clamp experiments where UDP and ATP were shown to
      sequentially activate whole-cell current in the same cell. The UDP-activated
      whole-cell current exhibited outward rectification with delay activation and
      inactivation at depolarizing and hyperpolarizing voltages, respectively. In
      addition, the UDP-evoked whole-cell current reversed near the equilibrium
      potential of Cl(-) in the presence of a Cl(-) gradient across the membrane, and
      was sensitive to 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS),
      indicating the activation of Ca(2+)-activated Cl(-) conductance. These
      characteristics were very similar to that of the ATP-activated whole-cell
      current. Taken together, our findings indicate the presence of distinct
      receptors, pyrimidinoceptors and P(2Y2) (P(2U)) receptors in mouse endometrial
      epithelial cells. These distinct receptors appear to converge on the same Ca(2+)
      dependent Cl(-) channels.

PMID- 10903432
TI  - Nuclear activation and translocation of mitogen-activated protein kinases
      modulated by ethanol in embryonic liver cells.
AB  - Activation and nuclear translocation of mitogen activated protein (MAP) kinases
      in ethanol-treated embryonic liver cells (BNLCL2) was investigated. The relative
      amount of MAPK proteins, MAP kinase activity and MAPK/LDH (lactate dehydrogenase)
      ratios were determined in nuclear and cytosolic fractions before and after serum
      stimulation. In ethanol-treated cells, serum-stimulated MAPK activation was
      potentiated in both cytosolic and nuclear fractions. Levels of both the p42 and
      p44 MAPK proteins increased in nuclear fractions from cells treated with ethanol
      alone for 24 h. Serum-stimulated nuclear translocation of both p42 and p44 MAPK
      was potentiated in ethanol-treated cells. Nuclear fractions from ethanol-treated
      cells had a modest increase in MAP kinase activity concurrent with the increased
      MAPK protein levels. The ratio of MAPK/LDH increased in nuclear fractions with
      increasing concentrations of ethanol and after serum stimulation. This further
      confirmed the nuclear translocation of MAPK and also demonstrated that it is not
      a non-specific effect of ethanol. These results demonstrate, for the first time,
      that in BNLCL2 liver cells ethanol treatment has dual effects. First, ethanol
      triggered nuclear translocation of MAPK without causing its activation. Second,
      it potentiated serum-stimulated activation and translocation of MAPK in the
      nucleus. These findings provide a novel mechanism through which ethanol may
      affect cellular and nuclear processes in liver cells.

PMID- 10903433
TI  - Regulation of the human fas promoter by YB-1, Puralpha and AP-1 transcription
      factors.
AB  - Fas (CD95/Apo-1) gene expression is dysregulated in a number of diseased states.
      Towards understanding the regulation of fas gene expression, we previously
      identified activator and repressor elements within the human fas promoter. Using
      a combination of expression screening and reporter gene assays, we have
      identified transcription factors which bind to these elements and thereby
      regulate transcription of the fas promoter. These are three single-stranded DNA
      binding proteins, YB-1, Puralpha and Purbeta and two components of the AP-1
      complex, c-Fos and c-Jun. c-Jun is a potent transcriptional activator of fas and
      stimulated expression levels up to 184-fold in reporter gene assays. Co
      expression with c-Fos abrogated c-Jun-mediated activation. YB-1 and Puralpha are
      transcriptional repressors of fas and decreased basal transcription by 60-fold in
      reporter gene assays. Purbeta was predominantly an antagonist of YB-1/Puralpha
      mediated repression. Overexpression of YB-1 and Puralpha in Jurkat cells was
      shown to reduce the level of cell surface Fas staining, providing further
      evidence that these proteins regulate the fas promoter. It has been suggested
      that YB-1 plays a role in cell proliferation as an activator of growth-associated
      gene expression. We have shown that YB-1 is a repressor of a cell death
      associated gene fas. These results suggest that YB-1 may play an important role
      in controlling cell survival by co-ordinately regulating the expression of cell
      growth-associated and death-associated genes.

PMID- 10903434
TI  - Mutational analysis of bli-4/kpc-4 reveals critical residues required for
      proprotein convertase function in C. elegans.
AB  - Kex2/subtilisin-like proteinase activity is required for the production of the
      adult cuticle in the nematode Caenorhabditis elegans. Deletion of the carboxy
      termini of four of the bli-4/kpc-4 convertase isoforms results in blistering of
      the adult cuticle. The blisters vary in severity (expressivity) and are not
      evident in all individuals (reduced penetrance). We have isolated 13 bli-4/kpc-4
      mutants that arrest development in late embryogenesis. Using a PCR-based
      heteroduplex technique, we have identified nucleotide changes responsible for
      eight of these lethal mutations. The lesions reside within the first 12 exons
      that are shared by all of the bli-4/kpc-4 gene products, with the majority of
      mutations clustered within the protease domain. This finding suggests that the
      protease domain represents a large mutable target. Among these mutations, allele
      h384 represents a molecular null mutant in which the catalytically essential
      serine residue (Ser415) is replaced by phenylalanine. Novel missense mutations
      that change the identity of amino acids evolutionary conserved in all
      kex2/subtilisin-convertases highlight critical residues essential for activity.
      We examined the functional activity of BLI-4/KPC-4 products expressed from
      several lethal mutants by testing their effect on the variable penetrance of
      blistering exhibited by the e937 allele. We found that the combination of a bli
      4/kpc-4 lethal mutation in trans to the bli-4(e937) mutation was sufficient to
      cause severe blistering in heteroallelic progeny, even in the presence of a known
      dominant suppressor.

PMID- 10903435
TI  - Structure of the human MMP-19 gene.
AB  - The recently identified MMP-19 belongs to the multi-protein family of zinc
      binding matrix metalloproteinases (MMP). In order to analyze its genomic
      organization and to identify transcription factor binding sites that may be
      involved in the regulation of human MMP-19 expression, the gene coding for MMP-19
      has been cloned and sequenced. The MMP-19 gene spans over 7.6kb and is composed
      of nine exons and eight introns. Furthermore, a 1.9kb fragment of 5'-flanking DNA
      was isolated and the transcription start point mapped. Nucleotide sequence
      analysis of its 5'-flanking region revealed several potential transcription
      factor binding sites typical of MMP promoters. Thus, a TATA-box, a consensus AP-1
      binding element, and a putative PEA3 site were identified. The 1.9kb MMP-19
      promoter fragment and several deletion constructs thereof were able to drive
      transcription of the luciferase reporter gene in transiently transfected CHO
      cells. Finally, it has been shown by an electrophoretic mobility shift assay that
      the AP-1 consensus sequence is able to bind a HeLa nuclear extract derived AP-1
      factor.

PMID- 10903436
TI  - Isolation and characterization of the human cyclin T1 promoter.
AB  - Cyclin T1 (CycT1) is a regulatory subunit of a general RNA polymerase II (RNAP
      II) elongation factor termed P-TEFb. The human immunodeficiency virus Tat protein
      directly associates with CycT1 to utilize CycT1/P-TEFb (also called TAK) for
      activation of RNAP II elongation of the integrated proviral genome. CycT1 mRNA
      and protein levels are induced in activated human peripheral blood lymphocytes
      and CycT1 protein levels are induced by a post-transcriptional mechanism when
      human U937 promonocytic cells are stimulated to differentiate into macrophage
      like cells. To investigate mechanisms that regulate CycT1 RNA expression, we
      isolated the CycT1 promoter. Multiple transcription start sites were identified
      within 330 nucleotides upstream of the ATG initiation codon at +1. The CycT1
      promoter lacks a TATA element and possesses high constitutive activity in plasmid
      transfection assays. Two distinct regions of the promoter were identified
      upstream of +1 that contain critical regulatory elements for CycT1 promoter
      function.

PMID- 10903437
TI  - Genomic organization and characterization of promoter function of the human CDK9
      gene.
AB  - CDK9 is the catalytic subunit of a general RNA polymerase II (RNAP II) elongation
      factor termed p-TEFb which is targeted by the human immunodeficiency virus (HIV)
      Tat protein to activate elongation of the integrated proviral genome. CDK9 mRNA
      and protein levels have been observed to be induced in activated peripheral blood
      lymphocytes, a cell type relevant to HIV infection. To investigate mechanisms
      that regulate CDK9 RNA expression, we isolated genomic sequences containing the
      human CDK9 gene and found that CDK9 coding sequences are interrupted by six
      introns. There is a major transcriptional start site located 79 nucleotides
      upstream of the ATG initiator codon at nucleotide +1. Nucleotides -352 to -1
      contain all the transcriptional regulatory elements needed for full promoter
      activity in transient expression assays. The CDK9 promoter contains features
      characteristic of a housekeeping gene, including GC-rich sequences and absence of
      a functional TATA element. The CDK9 promoter possesses high constitutive activity
      and may therefore have utility in expression vectors or gene therapy vectors.

PMID- 10903438
TI  - Fructose utilization and pathogenicity of Spiroplasma citri: characterization of
      the fructose operon.
AB  - Transposon Tn4001 mutagenesis of Spiroplasma citri wild-type (wt) strain GII-3
      led to the isolation and characterization of non-phytopathogenic mutant GMT 553.
      In this mutant, transposon Tn4001 is inserted within the first gene of the
      fructose operon. This operon comprises three genes. The first gene (fruR) codes
      for a putative transcriptional regulator protein belonging to the
      deoxyribonucleoside repressor (DeoR) family. Sequence similarities and functional
      complementation of mutant GMT 553 with different combinations of the wt genes of
      the fructose operon showed that the second gene (fruA) codes for the permease of
      the phosphoenolpyruvate:fructose phosphotransferase system (fructose PTS), and
      the third, fruK, for the 1-phosphofructokinase (1-PFK). Transcription of the
      fructose operon in wt strain GII-3 resulted in two messenger RNAs, one of 2.8kb
      and one of 3.8kb. Insertion of Tn4001 in the genome of mutant GMT 553 abolished
      transcription of the fructose operon, and resulted in the inability of this
      mutant to use fructose. Functional complementation experiments demonstrated that
      fructose utilization was restored with fruR-fruA-fruK, fruA-fruK or fruA only,
      but not with fruR or fruR-fruA. This is the first time that an operon for sugar
      utilization has been functionally characterized in the mollicutes.

PMID- 10903439
TI  - Efficient control of gene expression by a tetracycline-dependent transactivator
      in single Dictyostelium discoideum cells.
AB  - We established a tetracycline-regulated gene expression system that tightly
      controls expression of genes in Dictyostelium discoideum. The control elements
      are contained in two plasmid vectors, one being an integrated plasmid encoding a
      chimeric tetracycline-controlled transcriptional activator protein (tTA(s)(*)).
      The second component is an extrachromosomal plasmid harboring the gene of
      interest preceded by an inducible promoter. This promoter contains a tetracycline
      responsive element, which is the binding site for tTA(s)(*). Tetracycline
      prevents tTA(s)(*) from binding to the tetracycline-responsive element, rendering
      the promoter virtually silent. In the absence of tetracycline, tTA(s)(*) binds to
      its target sequence and strongly induces gene expression. The kinetics of
      activation and repression of the system were monitored using luciferase as a
      reporter. The results reveal efficient inhibition of gene expression by low
      concentrations of tetracycline and an induction of gene expression by several
      orders of magnitude within a few hours after removal of tetracycline. Green
      fluorescent protein (GFP) provided information about the effects of modulation of
      the tetracycline concentration on gene expression, at the single cell level,
      using fluorescence activated cell sorting (FACS). We also report that not all
      cells in a clonal population express the reporter gene.

PMID- 10903440
TI  - A family of genes with growth factor and adenosine deaminase similarity are
      preferentially expressed in the salivary glands of Glossina m. morsitans.
AB  - A cDNA library constructed from salivary glands of tsetse fly, Glossina morsitans
      morsitans (Diptera: Glossinidae), was differentially screened, and two related
      full-length cDNAs were molecularly characterized: tsetse salivary growth factor,
      TSGF-1 and TSGF-2. The cDNAs encode for open reading frames (ORFs) of 494 and
      506aa, respectively, and display an overall 45% amino acid identity and 61%
      similarity to one another. Both genes are preferentially expressed in the
      salivary glands of male and female adult flies. In addition to salivary glands,
      both transcripts can be detected from the gut tissue. Only transcripts specific
      for TSGF-2 are detected in ovary and testes tissues of adults as well as in
      puparia, while neither gene is expressed during the larval developmental stages.
      The N-terminal region of both putative proteins contains a hydrophobic sequence
      with secretory signal peptide characteristics, and analysis of proteins in saliva
      by Western blot indicates that both are secreted. Western blot analysis indicates
      that TSGF-1 is synthesized at significantly higher levels than TSGF-2. The
      deduced protein sequences of both cDNAs display extensive similarities to two
      other proteins: insect derived growth factor (IDGF) characterized from Sarcophaga
      peregrina with growth-factor activity, and atrial gland specific antigen (AGSA or
      MDSF) characterized from Apylasia californica. In addition to growth factor
      similarity, all four related proteins share the evolutionarily conserved amino
      acid residues associated with the enzymatic deamination of adenosine, which is
      shown here to be present in salivary gland extracts of tsetse. While both genes
      are present and expressed in G. m. morsitans and G. p. palpalis, only TSGF-1 is
      present in G. austeni. We present the molecular characteristics of the cDNAs,
      their genomic arrangement and their regulation of expression in different fly
      tissues and species. We discuss the potential role of these proteins in
      hemostatis and in African trypanosome transmission by different species of
      tsetse.

PMID- 10903441
TI  - dsRNA-mediated gene silencing in cultured Drosophila cells: a tissue culture
      model for the analysis of RNA interference.
AB  - RNA interference (RNAi) is a form of post-transcriptional gene silencing that has
      been described in a number of plant, nematode, protozoan, and invertebrate
      species. RNAi is characterized by a number of features: induction by double
      stranded RNA (dsRNA), a high degree of specificity, remarkable potency and spread
      across cell boundaries, and a sustained down-regulation of the target gene.
      Previous studies of RNAi have examined this effect in whole organisms or in
      extracts thereof; we have now examined the induction of RNAi in tissue culture. A
      screen of mammalian cells from three different species showed no evidence for the
      specific down-regulation of gene expression by dsRNA. By contrast, RNAi was
      observed in Drosophila Schneider 2 (S2) cells. Green fluorescent protein (GFP)
      expression in S2 cells was inhibited in a dose-dependent manner by transfection
      of dsRNA corresponding to gfp when GFP was expressed either transiently or
      stably. This effect was structure- and sequence-specific in that: (1) little or
      no effect was seen when antisense (or sense) RNA was transfected; (2) an
      unrelated dsRNA did not reduce GFP expression; and (3) dsRNA corresponding to gfp
      had no effect on the expression of an unrelated target transgene. This
      invertebrate tissue culture model should allow facile assays for loss of function
      in a well-defined cellular system and facilitate further understanding of the
      mechanism of RNAi and the genes involved in this process.

PMID- 10903443
TI  - In vivo and in vitro analysis of homodimerisation activity of the mouse Dazl1
      protein.
AB  - In Drosophila RNA-binding proteins play a fundamental role in key developmental
      pathways, such as sex determination. There is emerging evidence suggesting that
      RNA-binding proteins play a central role in regulation of development in mammals
      as well. We are interested in spermatogenesis as a model for cell differentiation
      and development in mammals. Two Y-encoded candidate spermatogenesis genes, RBMY
      and DAZ, have been isolated by positional cloning from infertile patients. They
      both encode putative RNA-binding proteins of the RRM (RNA recognition motif)
      type, and the high degree of conservation of both these gene families suggests an
      important role in spermatogenesis. Mice with a null allele for Dazl1, the mouse
      homologue of DAZ, are infertile due to a meiotic entry defect. Male flies mutant
      for boule, the Drosophila homologue of Dazl1, are infertile due to a G(2)/M
      meiotic block. However, no data has been published yet about the biochemical
      properties of the DAZ/DAZL1 proteins. We report here that Dazl1 is able to form
      homoheterodimers both in vivo and in vitro, that this activity is due to a novel
      protein-protein interaction domain, and that homotypic interaction activity is
      RNA-independent.

PMID- 10903442
TI  - Mouse NRH:quinone oxidoreductase (NQO2): cloning of cDNA and gene- and tissue
      specific expression.
AB  - The mouse NQO2 cDNA and gene with flanking regions were cloned and sequenced.
      Analysis of the primary structure of the mouse NQO2 protein revealed the presence
      of glycosylation, myristylation, protein kinase C and caseine kinase II
      phosphorylation sites. These sites are conserved in the human NQO2 protein. The
      mouse NQO2 gene promoter contains several important cis-elements, including the
      antioxidant response element (ARE), the xenobiotic response element (XRE), and an
      Sp1 binding site. Northern analysis of eight mouse tissues indicated wide
      variations in the expression of the NQO2 and NQO1 genes. NQO2 gene expression was
      higher in liver and testis compared with the NQO1 gene, which was highest in the
      heart. NQO1 gene expression was undetectable in the testis. Mouse kidney showed
      significantly higher expression levels of NQO1 compared with NQO2. Brain, spleen,
      lung, and skeletal muscle showed undetectable levels of NQO2 and NQO1 gene
      expression. NQO2 activity followed a more or less similar pattern of tissue
      specific expression as NQO2 RNA. Interestingly, the NQO2 activity remained
      unchanged in the NQO1-/-mice tissues compared with NQO1+/+ mice, with the
      exception of the liver. The livers from NQO1-/-mice showed a 45% increase in NQO2
      activity compared with the NQO1+/+ mice. The mouse NQO2 cDNA was subcloned into
      the pMT2 eukaryotic expression vector which, upon transfection in monkey kidney
      COS1 cells, produced a significant increase in NQO2 activity. Deletion of 54
      amino acids from the N-terminus of the mouse NQO2 protein resulted in the loss of
      NQO2 expression and activity in transfected COS1 cells. This indicates that
      deletion of exon(s) encoding the N-terminus of NQO2 from the endogenous gene in
      mouse embryonic (ES) stem cells should result in NQO2-null mice.

PMID- 10903444
TI  - Exploring redundancy in the yeast genome: an improved strategy for use of the cre
      loxP system.
AB  - Gene families having more than three members are a common phenomenon in the
      Saccharomyces cerevisiae genome. As yeast research enters the post-genome era,
      the development of existing deletion strategies is crucial for tackling this
      apparent redundancy, hence a method for performing rapid multiple gene
      disruptions in this organism has been developed. We constructed three replacement
      cassettes in which different selectable markers were placed between two loxP
      loci. Multiple deletions (of members of a gene family) were generated, in one
      strain, using sequential integration of different replacement markers (kanMX,
      LYS2, KlURA3 and SpHIS5). Their excision from the genome was performed
      simultaneously, as the final step, using a new cre recombinase vector, which
      carries the cycloheximide-resistance gene from Candida maltosa as a selectable
      marker. Our multiple gene deletion system significantly accelerates and
      facilitates the functional analysis process and is particularly useful for
      studying gene families in either laboratory or industrial yeast strains.

PMID- 10903446
TI  - The C. elegans apoptotic nuclease NUC-1 is related in sequence and activity to
      mammalian DNase II.
AB  - The Caenorhabditis elegans nuc-1 gene has previously been implicated in
      programmed cell death due to the presence of persistent undegraded apoptotic DNA
      in nuc-1 mutant animals. In this report, we describe the cloning and
      characterization of nuc-1, which encodes an acidic nuclease with significant
      sequence similarity to mammalian DNase II. Database searches performed with human
      DNase II protein sequence revealed a significant similarity with the predicted C.
      elegans C07B5.5 ORF. Subsequent analysis of crude C. elegans protein extracts
      revealed that wild-type animals contained a potent endonuclease activity with a
      cleavage preference similar to DNase II, while nuc-1 mutant worms demonstrated a
      marked reduction in this nuclease activity. Sequence analysis of C07B5.5 DNA and
      mRNA also revealed that nuc-1(e1392), but not wild-type animals contained a
      nonsense mutation within the CO7B5.5 coding region. Furthermore, nuc-1 transgenic
      lines carrying the wild-type C07B5.5 locus demonstrated a complete
      complementation of the nuc-1 mutant phenotype. Our results therefore provide
      compelling evidence that the C07B5.5 gene encodes the NUC-1 apoptotic nuclease
      and that this nuclease is related in sequence and activity to DNase II.

PMID- 10903445
TI  - A HECT domain ubiquitin ligase closely related to the mammalian protein WWP1 is
      essential for Caenorhabditis elegans embryogenesis.
AB  - The highly conserved ubiquitin/proteasome pathway controls the degradation of
      many critical regulatory proteins. Proteins are posttranslationally conjugated to
      ubiquitin through a concerted set of reactions involving activating (E1),
      conjugating (E2), and ligase (E3) enzymes. Ubiquitination targets proteins for
      proteolysis via the proteasome and may regulate protein function independent of
      proteolysis. We describe the cloning and functional analysis of new members of
      the HECT domain family of E3 ubiquitin ligases. Murine Wwp1 encoded a broadly
      expressed protein containing a C2 domain, four WW domains, and a catalytic HECT
      domain. A Caenorhabditis elegans gene was cloned encoding a HECT domain protein
      (CeWWP1), which was highly homologous to murine and human WWP1. Disruption of
      CeWwp1 via RNA interference yielded an embryonic lethal phenotype, despite the
      presence of at least six additional C. elegans genes encoding HECT domain
      proteins. The embryonic lethality was characterized by grossly abnormal
      morphogenesis during late embryogenesis, despite normal proliferation early in
      embryogenesis. CeWWP1 must therefore have unique and nonredundant functions
      critical for embryogenesis.

PMID- 10903447
TI  - Deoxyribonuclease II: structure and chromosomal localization of the murine gene,
      and comparison with the genomic structure of the human and three C. elegans
      homologs.
AB  - Deoxyribonuclease II (DNase II) has been implicated in diverse functions
      including degradation of foreign DNA, genomic instability, and in mediating the
      DNA digestion associated with apoptosis. The production of a mouse deleted for
      DNase II would clearly help to discriminate these functions. We have cloned and
      sequenced the mouse gene encoding DNase II. It was found to have a similar
      intron/exon structure to the human gene, although introns 3 and 5 are
      considerably shorter. The gene is located on mouse chromosome 8. The order of
      genes at this locus is mGCDH, mEKLF, mDNase II, mSAST, which is the same order
      that these genes are found on human chromosome 19. The GenBank database contains
      incorrect expressed sequence tags (ESTs) for the 3' end of the mouse mRNA.
      Furthermore, the gene structure of two of the three homologs in C. elegans is
      also incorrectly predicted in the database. We have established the correct
      intron/exon structure for these genes and show the conserved sequence and
      structure of the C. elegans, murine and human genes.

PMID- 10903448
TI  - Replication timing of the human X-inactivation center (XIC) region: correlation
      with chromosome bands.
AB  - The human genome is composed of long-range G+C% mosaic structures, which are
      thought to be related to chromosome bands. Replication timing during S phase is
      associated with chromosomal band zones; thus, band boundaries are thought to
      correspond to regions where replication timing switches. The proximal limit of
      the human X-inactivation center (XIC) has been localized cytologically to the
      junction zone between Xq13.1 and Xq13.2. Using PCR-based quantification of the
      newly replicated DNA from cell-cycle fractionated THP-1 cells, the replication
      timing in and around the XIC was determined at the genome sequence level. We
      found two regions where replication timing changes from the early to late period
      during S phase. One is located near a large inverted duplication proximal to the
      XIC, and the other is near the XIST locus. We propose that the 1Mb late
      replicated zone (from the large inverted duplication to XIST) corresponds to a G
      band Xq13.2. Several common characteristics were observed in the XIST region and
      the MHC class II-III junction which was previously defined as a band boundary.
      These characteristics included differential high-density clustering of Alu and
      LINE repeats, and the presence of polypurine/polypyrimidine tracts, MER41A, MER57
      and MER58B.

PMID- 10903449
TI  - The skeletal muscle alpha-actin gene of channel catfish (Ictalurus punctatus) and
      its association with piscine specific SINE elements.
AB  - The alpha-actin gene of channel catfish (Ictalurus punctatus) was cloned and
      sequenced. The gene has a similar organization and exhibited a high level of
      sequence similarity to those from other vertebrate animals. The upstream region
      of the alpha-actin gene included a TATA box, a CAAT box, three E-boxes, and a
      CArG box. Nested deletion segments containing these transcriptional motifs were
      fused to the reporter gene chloramphenicol acetyl transferase (CAT). Transfection
      of the clones into C2C12 cells indicated that all these motifs are required for
      transcriptional activities. The channel catfish alpha-actin gene is associated
      with two distinct short interspersed repetitive elements (SINEs). The first SINE
      element showed high levels of sequence similarity to the zebrafish Mermaid
      element, while the second SINE element is not similar to the Mermaid element
      except for an 8bp sequence CCCCGTGC suggesting their evolutionary linkage.
      However, the second SINE element appeared to co-exist with the Mermaid element in
      most cases and therefore was designated as the Merman element. Approximately 9000
      copies and 1200 copies of the Mermaid and Merman elements exist per haploid
      channel catfish genome, respectively. BLAST searches indicated that both the
      Mermaid and the Merman elements were frequently associated with gene sequences,
      mostly those of aquatic animals, suggesting their evolutionary origin in
      association with aquatic organisms and their function in shaping the evolution of
      genomes in aquatic animals.

PMID- 10903450
TI  - Identification of a novel silencer that regulates the myelin basic protein gene
      in neural cells.
AB  - The myelin basic protein gene produces two families of proteins, the golli
      proteins and the 'classic' myelin basic proteins from three transcription start
      sites (tsp). The golli proteins are expressed from the first tsp, and little is
      known about genetic elements that control its activity. We have examined elements
      that may regulate the expression of the golli products produced from this
      promoter in neural cell lines with constructs containing upstream portions of the
      first tsp by transient transfection assays. Three putative regulatory elements
      were identified, among them a 345bp novel silencer region, termed the golli
      silencer region (GSR), which was characterized in detail. This silencer was
      responsible for a significant (approx. 60%) inhibition of luciferase expression
      in PC12 cells. It was orientation-dependent and a double dose of this GSR
      completely abolished expression of the luciferase reporter activity.
      Transfections with deleted constructs identified three critical sites that bind
      at least two repressor proteins. We postulate that the silencer activity is the
      result of synergistic interactions between these repressor proteins and might
      involve the formation of a high-ordered protein-DNA structure.

PMID- 10903451
TI  - Expansion of mouse involucrin by intra-allelic repeat addition.
AB  - Involucrin, loricrin and the small proline-rich proteins (SPRRs) are precursors
      of the cornified envelope of terminally differentiated keratinocytes. The genes
      for these proteins are closely linked on mouse chromosome 3. Each of the proteins
      is encoded by a single exon and is largely composed of a segment of short tandem
      repeats. No size polymorphism of either loricrin or the SPRRs was observed. In
      contrast, involucrin was found in at least eight polymorphic forms of different
      size with molecular weights ranging from 51 to 82kDa. Two classes of involucrin
      alleles were identified. Size polymorphism of involucrin has resulted from the
      recent expansion of the segment of repeats in one class of alleles, but not in
      the other. In expanding alleles, repeats were added at a precise location within
      the segment of repeats, in a 5'-to-3' direction. A study of a large number of
      allele-specific markers, located on both sides of the site of repeat addition,
      revealed no evidence for recombination between any of the alleles examined.
      Expansion of the segment of repeats of the gene for mouse involucrin must result
      from an intra-allelic process controlled by a cis-acting element, active in one
      class of alleles, and inactive in the other.

PMID- 10903452
TI  - Isolation and characterization of three novel serine protease genes from Xenopus
      laevis.
AB  - Three novel cDNAs encoding serine proteases, that may play a role in early
      vertebrate development, have been identified from Xenopus laevis. These Xenopus
      cDNAs encode trypsin-like serine proteases and are designated Xenopus embryonic
      serine protease (Xesp)-1, Xesp-2, and XMT-SP1, a homolog of human MT-SP1. Xesp-1
      is likely to be a secreted protein that functions in the extracellular space.
      Xesp-2 and XMP-SP1 are likely to be type II membrane proteases with multidomain
      structures. Xesp-2 has eight low density lipoprotein receptor (LDLR) domains and
      one scavenger receptor cysteine-rich (SRCR) domain, and XMT-SP1 has four LDLR
      domains and two CUB domains. The temporal expressions of these serine protease
      genes show distinct and characteristic patterns during embryogenesis, and they
      are differently distributed in adult tissues. Overexpression of Xesp-1 caused no
      significant defect in embryonic development, but overexpression of Xesp-2 or XMT
      SP1 caused defective gastrulation or apoptosis, respectively. These results
      suggest that these proteases may play important roles during early Xenopus
      development, such as regulation of cell movement in gastrulae.

PMID- 10903453
TI  - Cloning and characterization of two overlapping genes in a subregion at 6q21
      involved in replicative senescence and schizophrenia.
AB  - Two new genes were cloned from region 6q21 and characterized. One gene, C6orf4-6,
      expresses three mRNA isoforms diverging at the 5' and 3' ends, and encodes two
      protein isoforms that differ by nine amino acids at their amino terminus. The
      second gene, C6UAS, is transcribed in the antisense orientation from the
      complementary strand of C6orf4-6. C6UAS overlaps the second exon of C6orf4, where
      the start codon of protein isoform 1 is located. C6UAS has no apparent ORF and
      most likely represents a structural RNA gene that is transcribed but not
      translated. This feature and the antisense polarity of transcription suggest that
      C6UAS could play a regulatory role on the expression of C6orf4, as indicated by a
      significant decrease of endogenous C6orf4 expression after transfection of C6UAS
      cDNA in human fibroblasts. Neither C6UAS nor C6orf4-6 genes show any homology
      with known human genes. The two genes were cloned from a subregion at 6q21
      containing a replicative senescence gene, a tumor suppressor gene and a gene
      involved in hereditary schizophrenia. In addition, the common fragile site FRA6F
      was mapped in the same region. Cloning and characterization of C6orf4-6 and C6UAS
      may help to clarify the structure and the functional role of this important
      region.

PMID- 10903454
TI  - Malpractice occurrence in emergency medicine: does residency training make a
      difference?
AB  - We evaluated the effects of Emergency Medicine (EM) residency training, EM board
      certification, and physician experience on the occurrence of malpractice claims
      and indemnity payments. This was a retrospective review of closed malpractice
      claims from a single insurer. Outcome measures included the occurrence of claims
      resulting in indemnity, indemnity amounts, and defense costs. Differences in the
      outcome measures were compared based on: EM residency training, EM board
      certification, EM residency training versus other residency training, and
      physician experience using both univariate and multivariate analyses. There were
      428 closed EM claims with indemnity paid in 81 (18.9%). Indemnity was paid in 22.
      4% of closed claims against non-EM residency-trained physicians, and in only
      13.3% against EM residency-trained physicians (p = 0.04). The total indemnity was
      $6,214,475. Non-EM trained physicians accounted for $4,440,951 (71.5%), EM
      residency-trained physicians accounted for $1,773,524 (28.5%). The average
      indemnity was $76,721 and the average defense cost was $17,775. There were no
      significant differences in the mean indemnity paid per closed claim or the mean
      cost to defend a closed claim when comparing EM-trained and non-EM residency
      trained physicians. The total cost (indemnity + defense costs) per physician-year
      of malpractice coverage was $4,905 for non-EM residency-trained physicians and
      $2,212 for EM residency-trained physicians. EM residency-trained physicians
      account for significantly less malpractice indemnity than non-EM residency
      trained physicians. This difference is not due to differences in the average
      indemnity but is due to significantly fewer closed claims against EM residency
      trained physicians with indemnity paid. This results in a cost per physician-year
      of malpractice coverage for non-EM residency-trained physicians that is over
      twice that of EM residency-trained physicians.

PMID- 10903455
TI  - Emergency department personnel accuracy at estimating patient satisfaction.
AB  - We investigated the congruence between emergency department (ED) personnel
      estimations of patient satisfaction and actual patient satisfaction. Actual
      patient satisfaction was assessed via telephone interview. Before the findings
      were disseminated, ED personnel were asked to "predict" the results by estimating
      the average rating they believed patients gave for each of the 22 indicators.
      Surveys were obtained from 478 of 1,139 (42.1%) patients and 59 of 76 (77.6%) ED
      personnel. ED personnel consistently estimated average satisfaction scores to be
      significantly lower than what patients actually reported across 19 of the 22
      indicators. ED personnel grossly overestimated average patient length of stay
      (LOS) (5.7 h vs. 3.5 h actual). Results suggest that ED personnel consistently
      estimated patients to be less satisfied than they actually were across multiple
      domains. Moreover, ED personnel estimated average LOS to be more than 2 h longer
      than patients' actual LOS. Hypotheses for why this bias occurred are discussed.

PMID- 10903456
TI  - Patient satisfaction with pain management does not correlate with initial or
      discharge VAS pain score, verbal pain rating at discharge, or change in VAS score
      in the Emergency Department.
AB  - The aim of this study was to correlate patient satisfaction with pain management
      in the Emergency Department (ED) with initial and discharge visual analog scale
      (VAS) pain score, verbal pain rating at discharge, and change in VAS pain score
      between presentation and discharge. It was conducted as a prospective
      observational study of patients who presented to an urban, adult ED experiencing
      pain and who were later discharged. Fifty-four patients completed the study of
      whom 70% rated the management of their pain as 'good' or 'very good.' There was
      no correlation between patient satisfaction with pain management initial VAS pain
      score, discharge VAS pain score, verbal rating of pain at discharge, or change in
      VAS pain score between presentation and discharge. The study suggests that
      patient satisfaction with pain management does not correlate with initial or
      discharge VAS pain score, verbal rating of pain at discharge or change in pain
      score in the ED. Therefore, information about the quality of analgesia provided
      in an ED cannot be inferred from patient satisfaction surveys.

PMID- 10903457
TI  - Improving the emergency department detection rate of domestic violence using
      direct questioning.
AB  - The purpose of this study was to compare the domestic violence (DV) rate
      identified with simple direct questioning to a historical cohort of patients
      receiving routine emergency department (ED) care. One thousand ED charts of
      female patients were retrospectively reviewed. Each patient in the prospective
      cohort was asked five DV specific questions. The historical cohort revealed a DV
      prevalence rate of 0.4%. The prospective study group of 302 patients identified
      11 (3.6%) patients who admitted to acute DV on direct questioning. Ten of these
      patients accepted help. Twenty (6.6%) were identified as probable DV and 12 (4%)
      admitted to past violence. The total number of victims of DV, past, present, and
      probable was 43 (14.2%). This increase in detection from 0.4% (4/1000) to 14.2%
      (43/302) is significant at p < 0.001. Only 1.3% of patients refused to
      participate in the DV specific questions. The conclusion of the study indicated
      that the use of simple, direct questioning significantly improves the detection
      rate of DV in the ED.

PMID- 10903458
TI  - Safety and efficacy of the Rapid Four-Step Technique for cricothyrotomy using a
      Bair Claw.
AB  - The Rapid Four-Step Technique (RFST) has been demonstrated to be faster than
      standard open crico thyrotomy technique, but may have a higher incidence of
      cricoid injury with tracheal hook traction applied caudad. The "Bair Claw" is a
      novel device that may help eliminate these complications. This randomized,
      experimental trial used a fresh-frozen cadaver model of cricothyrotomy to compare
      speed and safety between RFST using a Bair Claw and standard open technique.
      Outcome measures included time to definitive airway, size of largest endotracheal
      (ET) tube able to be passed, and incidence of complications. We observed that
      RFST using a Bair Claw was significantly faster than standard open technique.
      There was no significant difference with regard to size of ET tube able to be
      passed with RFST using a Bair Claw versus standard open technique, and there was
      no damage to trachea or larynx observed with either technique. We concluded that
      RFST using a Bair Claw is faster and appears to be equally safe when compared to
      standard open technique in a fresh-frozen cadaver model of cricothyrotomy. The
      two techniques were equal with regard to maximal ET tube size.

PMID- 10903459
TI  - Pyocystis: two case reports of patients in renal failure.
AB  - Two cases of pyocystis in patients in end-stage renal disease are reported.
      Pyocystis is a recognized complication of urinary diversion procedures, but also
      occurs in anuric or oliguric hemodialysis patients. The treatment differs from
      ordinary cystitis, requiring catheterization, bladder irrigation, and
      intravesical antibiotic instillation. When undiagnosed, pyocystis may progress to
      sepsis and death.

PMID- 10903460
TI  - Generalized seizure in a 30-year-old man with presumed intracranial hemorrhage: a
      case report.
AB  - A 30-year-old man presented to the emergency department of another institution
      with recurrent episodes of generalized tonic-clonic seizures. He was found to be
      hypocalcemic and was treated with an intravenous infusion of calcium followed by
      Dilantin. A computed tomography scan of the head was obtained, and the patient
      was transferred to our institution for neurosurgical evaluation and possible
      intervention of what was thought to be bilateral intracranial hemorrhages. After
      further evaluation at our institution, the diagnoses of hypoparathyroidism
      associated with hypocalcemic seizures and basal ganglia calcifications were
      established on both clinical and biochemical grounds. This case report discusses
      the clinical presentation, pathogenesis, diagnostic work-up, and management of
      hypoparathyroidism and associated seizures, highlighting the possible diagnostic
      and therapeutic pitfalls that are most pertinent to the emergency physician.

PMID- 10903461
TI  - Acute arterial spasm in an extremity caused by inadvertent intra-arterial
      injection successfully treated in the emergency department.
AB  - We present a case of limb ischemia in a young man. For acute alcohol withdrawal,
      this patient was given chlordiazepoxide (Librium) through an angiocatheter
      inadvertently placed into a brachial arterial line. This caused severe spasm of
      the brachial artery and its branches. These findings were confirmed by
      angiography. Successful treatment occurred with intra-arterial papaverin.

PMID- 10903462
TI  - Pneumomediastinum acquired by glass blowing.
AB  - Pneumomediastinum is uncommon. We present a case of spontaneous
      pneumomediastinum, which occurred in a young man whose profession is glass
      blowing. He presented not only with typical complaints of chest pain and
      odynophagia, but also with the unusual complaint of a "foreign body" sensation in
      the middle of his chest.

PMID- 10903463
TI  - An unusual presentation of ascending aortic arch dissection.
AB  - The following case report is that of a young man who collapsed on a golf course
      during a heat advisory. The prehospital presentation suggested that the patient
      was suffering from heat exhaustion. In the Emergency Department, the patient's
      condition continued to deteriorate despite aggressive rehydration and cooling
      efforts. Aggressive evaluation and treatment of the patient led to the diagnosis
      of an acute painless dissection of the ascending aorta.

PMID- 10903464
TI  - Infant hypernatremia: a case report.
AB  - A 7-month-old infant presented to the emergency department with diarrhea,
      vomiting, and decreased activity. The infant was febrile, tachycardic,
      tachypneic, lethargic, and had a prolonged capillary refill. Initial serum sodium
      was 197 mmol/L. Ultimately, the infant was diagnosed with central diabetes
      insipidus complicated by severe dehydration secondary to rotavirus infection. A
      brief review of infant hypernatremia and its evaluation and treatment in the
      emergency department follows.

PMID- 10903466
TI  - Detection of isopropyl alcohol in a patient with diabetic ketoacidosis.
AB  - A 29-year-old man presented to the Emergency Department with acute mental status
      changes. He was unable to give a history. He was found to be in diabetic
      ketoacidosis, although his family reported no prior history of diabetes. A toxic
      exposure work-up revealed the presence of isopropyl alcohol in the patient's
      blood. His condition improved with treatment of the ketoacidosis, and he
      subsequently denied any exposure to isopropyl alcohol prior to presentation to
      the hospital. This case provides further support to a growing body of evidence
      that the detection of isopropyl alcohol may not represent an acute ingestion but,
      rather, a byproduct of acetone metabolism in certain disease states.

PMID- 10903465
TI  - Suicide by ingestion of a CCA wood preservative.
AB  - Chromated-copper-arsenate (CCA) is a compound used worldwide for wood
      preservation. Occupational hazards from chronic exposure to CCA are well known,
      but acute ingestion of CCA wood preservative is very rare. We describe a case of
      suicide by ingestion of a CCA wood preservative. A 33-year-old man attempted
      suicide by ingesting an unknown liquid, later identified as a CCA wood
      preservative, 75 min before his arrival in the emergency department. He was in
      severe respiratory distress, drooling, tachycardic, and hypotensive. There was an
      orange color on the palms of both hands. Severe, green colored burns of the
      buccal mucosa were observed. He was intubated shortly after arrival. The larynx
      was edematous, but a 7-mm endotracheal tube was successfully introduced. Blood
      tests revealed partially compensated metabolic acidosis. The patient deteriorated
      rapidly; the systolic blood pressure dropped to 70 mmHg, and he passed bloody
      diarrhea. He developed multiple premature atrial contractions and
      supraventricular tachycardia, and later in the intensive care unit, refractory
      ventricular tachycardia and ventricular fibrillation. The patient was declared
      dead 212 h after his arrival. Unfortunately, postmortem blood levels of heavy
      metals and autopsy were not performed because of refusal by the family for
      religious reasons.

PMID- 10903467
TI  - Ingestion of antacid tablets (Rennie) and acute confusion.
AB  - The authors describe a case of milk-alkali syndrome in a man who consumed antacid
      tablets (Rennie) for chronic epigastric pain. Simultaneous occurrence of
      hypercalcemia, metabolic alkalosis, and renal insufficiency, in conjunction with
      the appropriate history of ingestion of calcium carbonate-containing antacids,
      was suggestive of the syndrome. The syndrome became uncommon with the advent of
      modern ulcer therapy, but currently is increasing in frequency with the calcium
      supplementation drugs taken to prevent osteoporosis. This syndrome may produce
      life-threatening hypercalcemia.

PMID- 10903468
TI  - Rare Jatropha multifida intoxication in two children.
AB  - Two children were admitted to the Emergency Department (ED) after ingesting a
      large amount of fruit of a plant identified as Jatropha multifida. They were
      mildly obtunded, had intractable vomiting, and seemed dehydrated. Intravenous
      fluid replacement and urine alkalinization were initiated. After stabilization,
      their 5-day hospital stays were uneventful except for a subclinical rise of liver
      enzymes. Jatropha species contain the toxalbumin ricin, which causes severe
      vomiting and diarrhea, dehydration, shock, and renal and hepatic impairment.
      Ricin also has cardiotoxic and hemolytic effects and several deaths have been
      documented. Children are attracted by the shape and the color of the Jatropha
      fruits. Mortality can be prevented by immediate fluid and electrolyte
      replacement.

PMID- 10903469
TI  - Runaway pacemaker: a case report and review.
AB  - We describe a case of runaway pacemaker. The differential diagnosis is discussed
      and a review of the literature is included for the diagnosis and treatment of
      pacemaker mediated tachycardia and runaway pacemaker.

PMID- 10903471
TI  - Abnormal paraspinal fat stripe on plain radiograph.

PMID- 10903470
TI  - Stridor.

PMID- 10903472
TI  - Mode analysis of binding of fatty acids to mammalian DNA polymerases.
AB  - We previously reported that unsaturated long-chain fatty acids were potent DNA
      polymerase inhibitors (Y. Mizushina et al., J. Biol. Chem. 274 (1999) 25599
      25607). In those experiments, the question remained of whether metastable oil
      droplets (liposomal vesicles) of the unsaturated long-chain fatty acids can non
      specifically inhibit the polymerase activity. We report here that only the
      soluble fatty acid monomers of linoleic acid or nervonic acid could affect the
      activities of mammalian DNA polymerases, and the metastable oil droplets could
      not. When we consider the facts that nuclear membranes are a kind of liposomal
      vesicles, that free fatty acids occur only at the moment the lipids are digested,
      and that the DNA polymerization possibly occurs on the nuclear membranes, the
      data shown here are suggestive regarding the mechanism of regulation of DNA
      polymerization in vivo.

PMID- 10903473
TI  - Metabolism of highly unsaturated n-3 and n-6 fatty acids.

PMID- 10903474
TI  - Intestinal absorption of cholesterol is mediated by a saturable, inhibitable
      transporter.
AB  - Although the mechanism by which dietary cholesterol is absorbed from the
      intestine is poorly understood, it is generally accepted that cholesterol is
      absorbed from bile acid micelles in the jejunum. Once inside the enterocytes,
      cholesterol is esterified by the action of acyl-coenzyme A:cholesterol
      acyltransferase (ACAT), assembled into chylomicrons, and secreted into the lymph.
      In this work, mechanistic aspects of cholesterol absorption were probed using
      compounds that block cholesterol absorption in hamsters. Sterol glycoside
      cholesterol absorption inhibitors, exemplified by L-166,143, (3 beta, 5
      alpha,25R)-3-[(4", 6"-bis[2-fluoro-phenylcarbamoyl]-B-D-cellobiosyl)oxy]
      spirostan -11-on e, potently blocked absorption of radioactive cholesterol, and
      the potencies of several analogs correlated with their ability to lower plasma
      cholesterol. Each molecule of L-166,143 blocked the uptake of 500 molecules of
      cholesterol, rendering it unlikely that the inhibitor interacts directly with the
      cholesterol or bile acid. Radiolabeled L-166,143 bound to the mucosa and binding
      was blocked by active, but not inactive, cholesterol absorption inhibitors.
      Subtle changes in the structure of sterol glycosides yielded large changes in
      their ability to block both cholesterol absorption and binding of radiolabeled L
      166,143. Large species-to-species variation in potency was also observed. These
      lines of evidence support the interpretation that dietary cholesterol is absorbed
      via a specific transporter found in the intestinal mucosa.

PMID- 10903475
TI  - A target for cholesterol absorption inhibitors in the enterocyte brush border
      membrane.
AB  - Uptake of cholesterol by the intestinal absorptive epithelium can be selectively
      blocked by specific small molecules, like the sterol glycoside, L-166,143.
      Furthermore, (3)H-labeled L-166,143 administered orally to hamsters binds
      specifically to the intestinal mucosa, suggesting the existence of a cholesterol
      transporter. Using autoradiography, the binding site of (3)H-L-166,143 in the
      hamster small intestine was localized to the very apical aspect of the absorptive
      epithelial cells. Label was competed by non-radioactive L-166,143 and two
      structurally distinct cholesterol absorption inhibitors, suggesting a common site
      of action for these compounds. L-166,143 blocked uptake of (3)H-cholesterol into
      enterocytes in vivo, as demonstrated by autoradiography, suggesting that it
      inhibits a very early step of cholesterol absorption, incorporation into the
      brush border membrane. This conclusion was confirmed by studies in which
      intestinal brush borders were isolated from hamsters dosed with (3)H-cholesterol
      in the presence or absence of L-166,143. Uptake of (3)H-cholesterol into the
      membranes was substantially inhibited by the compound. In contrast, an inhibitor
      of acyl CoA:cholesterol acyltransferase, did not affect uptake of (3)H
      cholesterol into the brush border membranes. These results strongly support the
      existence of a specific transporter that facilitates the movement of cholesterol
      from bile acid micelles into the brush border membranes of enterocytes.

PMID- 10903476
TI  - Structure of a biologically active fragment of human serum apolipoprotein C-II in
      the presence of sodium dodecyl sulfate and dodecylphosphocholine.
AB  - We have studied the three-dimensional structure of a biologically active peptide
      of apolipoprotein C-II (apoC-II) in the presence of lipid mimetics by CD and NMR
      spectroscopy. This peptide, corresponding to residues 44-79 of apoC-II, has been
      shown to reverse the symptoms of genetic apoC-II deficiency in a human subject. A
      comparison of alpha-proton secondary shifts and CD spectroscopic data indicates
      that the structure of apoC-II(44-79) is similar in the presence of
      dodecylphosphocholine and sodium dodecyl sulfate. The three-dimensional structure
      of apoC-II(44-79) in the presence of sodium dodecyl sulfate, determined by
      relaxation matrix calculations, contains two amphipathic helical domains formed
      by residues 50-58 and 67-75, separated by a non-helical linker centered at Tyr63.
      The C-terminal helix is terminated by a loop formed by residues 76-79. The C
      terminal helix is better defined and has a larger hydrophobic face than the N
      terminal helix, which leads us to propose that the C-terminal helix together with
      the non-helical Ile66 constitute the primary lipid binding domain of apoC-II(44
      79). Based on our structure we suggest a new mechanism of lipoprotein lipase
      activation in which both helices of apoC-II(44-79) remain lipid bound, while the
      seven-residue interhelical linker extends away from the lipid surface in order to
      project Tyr63 into the apoC-II binding site of lipoprotein lipase.

PMID- 10903477
TI  - Enrichment and localization of ganglioside G(D3) and caveolin-1 in shed tumor
      cell membrane vesicles.
AB  - Tumor cell ganglioside shedding has been implicated in the process of tumor
      formation. Previously, we identified three forms of tumor ganglioside shedding:
      micelles, monomers and membrane vesicles. Here, we have explored the membrane
      vesicle form of ganglioside shedding, using a newly identified human ovarian
      carcinoma cell line, CABA I. These cells synthesize and express a spectrum of
      gangliosides, including the disialoganglioside, G(D3). Immunostaining using the
      monoclonal antibody R24 confirmed G(D3) expression and its presence in the plasma
      membrane of these cells. Cellular gangliosides were detected in the culture
      supernatant by HPTLC autoradiography, confirming an active shedding rate of 3% of
      cellular gangliosides/24 h. CABA I cell membranes also express caveolin-1, a
      characteristic protein marker for caveolae, which was detected by flow cytometric
      analysis and by Western blotting in both the cell membranes and the isolated
      membrane vesicles. To further define the expression of G(D3) and caveolin-1, we
      used immunogold electron microscopy. This revealed localization of G(D3) in small
      clusters in the plasma membrane as well as enrichment and localization of
      ganglioside G(D3) and caveolin-1 in shed membrane vesicles, with 58-78% of
      vesicles carrying both G(D3) and caveolin-1. Together, these results suggest that
      membrane vesicle shedding originates in plasma membrane domains enriched in
      gangliosides and caveolin-1.

PMID- 10903478
TI  - The capacity of various non-esterified fatty acids to suppress lipid transfer
      inhibitor protein activity is related to their perturbation of the lipoprotein
      surface.
AB  - Lipid transfer inhibitor protein (LTIP) regulates cholesteryl ester transfer
      protein (CETP) activity by selectively impeding lipid transfer events involving
      low density lipoproteins (LDLs). We previously demonstrated that LTIP activity is
      suppressed in a dose-dependent manner by sodium oleate and that its activity can
      be blocked by physiological levels of free fatty acids [R.E. Morton, D. J.
      Greene, Arterioscler. Thromb. Vasc. Biol. 17 (1997)]. These data further
      suggested that palmitate has greater LTIP suppressive activity than oleate. In
      this report we define the ability of the major non-esterified fatty acids (NEFAs)
      in plasma to modulate LTIP activity. The greater suppression of LTIP activity by
      palmitate compared to oleate noted above was also seen in lipid transfer assays
      with various lipoprotein substrates and in the presence of albumin, showing that
      the relative effects of these two NEFAs are independent of assay conditions. To
      assess the effect of other NEFAs on LTIP activity, pure NEFAs were added to
      assays containing (3)H-cholesteryl ester labeled LDLs, unlabeled high density
      lipoproteins (HDLs) and CETP+/-LTIP. Whereas myristate, palmitate, stearate,
      oleate and linoleate stimulated CETP activity to varying extents, all NEFAs
      suppressed LTIP activity. Among these NEFAs, LTIP suppressive activity was
      greatest for the long-chain saturated and monounsaturated NEFAs. In contrast,
      linoleate and myristate were poor inhibitors of LTIP activity. The effects of
      increasing amounts of a given NEFA on LTIP activity correlated well with the
      increase in LDL negative charge induced by that NEFA, yet this relationship was
      unique for each NEFA, especially stearate. Notably, as measured by fluorescence
      anisotropy, the suppression of LTIP was highly and negatively correlated with the
      decreased order in the molecular packing of lipoprotein surface phospholipids
      caused by all NEFAs. Long-chain, saturated and monounsaturated NEFAs appear to be
      most effective in this regard partly because of their preferential association
      with LDLs where LTIP inhibition likely takes place. We hypothesize that NEFAs
      suppress LTIP activity by perturbing the surface properties of LDLs and
      counteracting the heightened molecular packing normally caused by LTIP. Diets
      rich in long-chain saturated and monounsaturated fatty acids may lead to a
      greater suppression of LTIP activity in vivo, which would allow LDLs to
      participate more actively in CETP-mediated lipid transfer reactions.

PMID- 10903479
TI  - Inhibition of hepatic stearoyl-CoA desaturase activity by trans-10, cis-12
      conjugated linoleic acid and its derivatives.
AB  - Conjugated linoleic acid (CLA) has been reported to decrease stearoyl-CoA
      desaturase (SCD) activity by decreasing mRNA expression. This investigation was
      designed to determine whether structurally related compounds of CLA have a direct
      inhibitory effect on SCD activity. Trans-10,cis-12 CLA had strong inhibitory
      activity on SCD while cis-9,trans-11, and trans-9,trans-11 isomers had no effect.
      Trans-10 octadecenoate was not inhibitory, whereas cis-12 octadecenate was
      inhibitory, but not as effective as trans-10,cis-12 CLA. Of the oxygenated
      derivatives, 9-peroxy-cis/trans-10, trans-12 octadecadienoate was a more
      effective inhibitor than trans-10,cis-12 CLA, whereas 9-hydroxy-trans-10, cis-12
      octadecadienoate was less effective. Interestingly, cis-11 octadecadienoate and
      cis-12 octadecen-10-ynoate were slightly inhibitory. However, trans-9 and trans
      11 octadecenoates, and trans-9,cis-12 octadecadienoate were all inactive under
      test condition, as were linoleate, oleate, and arachidonate. Derivatives of CLA
      acid modified to alcohol, amide or chloride were all inactive. A cis-12 double
      bond appears to be a key structural feature for inhibiting SCD activity,
      especially when coupled with a trans-10 double, whereas a cis-11 double bond is
      less effective.

PMID- 10903480
TI  - Formation of oxysterols from different pools of cholesterol as studied by stable
      isotope technique: cerebral origin of most circulating 24S-hydroxycholesterol in
      rats, but not in mice.
AB  - In order to study the origin of different oxysterols in the circulation, in
      particular 24S-hydroxycholesterol, different pools of cholesterol in rat and
      mouse were labelled by feeding the animals with a diet supplemented with 0.3 or
      0.5% hexadeuterium-labelled cholesterol, respectively, for 10 days. The
      incorporation of deuterium label in cholesterol and different oxysterols was
      measured by combined gas chromatography-mass spectrometry in selected tissues and
      in the circulation. In both rat and mouse, a high incorporation of label was
      found in cholesterol present in serum and liver (up to 77%). Incorporation of
      label was similar in 7 alpha- and 7 beta-hydroxycholesterol of the same origin.
      There was no significant incorporation of deuterium in brain cholesterol, and
      little or no incorporation in the brain oxysterols investigated, in both animals.
      In the testis, the incorporation of the deuterium label in cholesterol was less
      than half of that in the liver, with similarly reduced labelling of the
      testicular oxysterols. 24S-Hydroxycholesterol in the circulation contained a
      deuterium content that was about 50% of that of serum and liver cholesterol in
      the mouse experiment and about 30% in the rat experiment. Thus, about 50% of
      circulating 24S-hydroxycholesterol in the mouse and about 70% of this fraction in
      the rat must originate from pools of cholesterol that are not in equilibrium with
      plasma and liver cholesterol. The liver is probably responsible for a
      considerable part of the extracerebral formation of 24S-hydroxycholesterol, since
      this organ contained detectable amounts of 24S-hydroxycholesterol with a
      relatively high incorporation of deuterium in both animal species. The results
      are consistent with a cerebral origin of more than half of the 24S
      hydroxycholesterol in the circulation of rats, but not in mice.

PMID- 10903481
TI  - Arachidonic acid stimulates cell growth and forms a novel oxygenated metabolite
      in Candida albicans.
AB  - Infection of human tissues by Candida albicans has been reported to cause the
      release of arachidonic acid (AA), eicosanoids and other proinflammatory mediators
      from host cells. Therefore, we investigated the interaction of this pathogen with
      AA. AA stimulated cell growth at micromolar concentrations when used as a sole
      carbon source. Moreover, it selectively inhibited the antimycin A-resistant
      alternative oxidase. [1-(14)C]AA was completely metabolised by C. albicans. Only
      one-seventh of the radioactivity metabolised was found in CO(2), whereas two
      thirds occurred in carbohydrates suggesting a predominant role of the glyoxalate
      shunt of citrate cycle. About 1% of radioactivity was found in polar lipids
      including eicosanoids. A novel AA metabolite, which revealed immunoreactivity
      with an antibody against 3(R)-hydroxy-oxylipins, was identified as 3, 18
      dihydroxy-5,8,11,14-eicosatetraenoic acid. Using immunofluorescence microscopy,
      endogenous 3(R)-hydroxy-oxylipins were found in hyphae but not in yeast cells.
      Such compounds have recently been shown to be connected with the sexual stage of
      the life cycle of Dipodascopsis uninucleata. Together, we propose that infection
      mediated release of AA from host cells may modulate cell growth, morphogenesis
      and invasiveness of C. albicans by several modes. A better understanding of its
      role is thus promising for novel approaches towards the treatment of human
      mycoses.

PMID- 10903482
TI  - Inhibition of lipoprotein lipase activity by sphingomyelin: role of membrane
      surface structure.
AB  - We have recently shown that sphingomyelin (SM) strongly inhibits lipoprotein
      lipase (LPL)-mediated lipolysis in monolayers and emulsion particles. To further
      evaluate how SM modulates LPL activity on the emulsion surface, the relationship
      between membrane surface structure and LPL activity was investigated. We measured
      fluorescence anisotropy of 1-palmitoyl-2-[3-(diphenylhexatrienyl)propionyl]-sn-3
      phosphati dylcho line, probing surface acyl chain fluidity, and fluorescence
      lifetime of N-(5-dimethylaminonaphthalene-1-sulfonyl)dipalmitoylphosphatidylethan
      olamine in H(2)O and D(2)O buffer, assessing the degree of hydration in the head
      group region. The results revealed that incorporation of egg SM into triolein-egg
      phosphatidylcholine emulsions markedly increased acyl chain order and decreased
      head group hydration of the surface monolayers. In contrast, cholesterol was
      shown to increase head group hydration despite a strong increase in acyl chain
      order. The close correlation between the apparent K(m) values of LPL and the
      degree of head group hydration indicated that LPL interacts with the head group
      region rather than with the hydrophobic interior of the surface monolayers.
      However, apparent V(max) did not show a simple correlation with any surface
      structure, and the finding in which SM had no effect on apparent V(max) of medium
      chain triglyceride emulsions suggested that the hydrophobic interaction between
      acyl chains of SM and triglyceride at the emulsion surface is important for
      determining the apparent V(max). These results showed conclusively that SM
      inhibits LPL activity mainly by changing the emulsion surface structure and not
      by a specific interaction between SM and LPL.

PMID- 10903484
TI  - And a good time was had by all!

PMID- 10903483
TI  - Headgroup specificity of lecithin cholesterol acyltransferase for monomeric and
      vesicular phospholipids.
AB  - In this study, we investigated how the nature of the phospholipid head group and
      the macromolecular structure of the phospholipid, either as a monomer or
      incorporated into a lipid matrix, influence the activity of lecithin cholesterol
      acyltransferase (LCAT). As substrates we used 1,2-bis-(1-pyrenebutanoyl)
      phosphatidylcholine, 1, 2-bis-(1-pyrenebutanoyl)-phosphatidylethanolamine and 1,
      2-bis-(1-pyrenebutanoyl)-phosphatidyl-alcohols, either as monomers or
      incorporated into small unilamellar vesicles consisting of
      dipalmitoylphosphatidylcholine ether. The rate of hydrolysis of the pyrene
      labeled phospholipids was determined both by fluorescence and by high performance
      liquid chromatography. V(max) and K(m) were calculated for the different
      substrates. The data show that V(max) is 10- to 30-fold higher for the hydrolysis
      of monomeric phosphatidylcholine (PC) compared to phosphatidylethanolamine (PE)
      and the phosphatidylalcohols, while K(m) values are comparable. When the
      fluorescent substrates were incorporated into dipalmitoylphosphatidylcholine
      ether vesicles, we observed a 4- to 10-fold increase of V(max) for PE and the
      phosphatidylalcohols, and no significant change for K(m). V(max) for PC remained
      the same. Natural LCAT mutants causing Fish-Eye Disease (FED) and analogues of
      these mutants expressed in Cos-1 cells, had similar activity on monomeric PC and
      PE. These data suggest that the activity of LCAT is determined both by the
      molecular structure of the phospholipid and by its macromolecular properties. The
      LCAT activity on monomeric substrates decreases as: phosphatidylcholine&z.
      Gt;phosphatidylethanolamine congruent withphosphatidylpropanol congruent
      withphosphatidylethanol congruent withphosphatidylethyleneglycol. The
      incorporation of PE and the phosphatidylalcohols into a matrix of
      dipalmitoylphosphatidylcholine decreases the specificity of the phospholipid head
      group.

PMID- 10903485
TI  - New challenges for the Canadian Thoracic Society.
AB  - OBJECTIVES: Two 12-week, randomized, double-blind, parallel-group studies were
      performed to compare the efficacy and safety of once- and twice-daily dosing of
      fluticasone propionate (FP) in the treatment of mild to moderate asthma,
      considered to require the equivalent of either 200 or 500 ug of FP daily.
      PATIENTS AND METHODS: In study A, 461 patients with asthma received FP either 200
      ug once daily or 100 ug twice daily. In study B, 443 patients with asthma
      received FP, either 500 ug once daily or 250 ug twice daily. RESULTS: In both
      studies, regardless of the treatment regimen to which patients were randomly
      assigned, small improvements over baseline were observed in morning peak
      expiratory flows (PEF)and forced expiratory volume in 1 s (FEV1) following 12
      weeks of treatment. In study A, the mean morning PEF improved by 2.4% and 4.3%
      (once daily versus twice daily, P=0.008). In study B, the mean morning PEF
      improvement was 0.2% and 3.7% (once daily versus twice daily, P<0.001). For both
      studies, the increases observed in FEV1 were not significant (P = not
      significant). The incidence of exacerbations of asthma and related events was 13%
      and 5%, respectively, in the patients with mild asthma for the once-daily group
      versus the twice-daily group; these exacerbations were 12% and 10%, respectively,
      in patients with moderate asthma. Otherwise, the incidence and types of adverse
      events were comparable for the two treatment regimens. Although twice-daily
      dosing demonstrated small but statistically significant improvements over once
      daily dosing, patients of both groups generally maintained a good level of asthma
      control on both regimens according to current treatment guidelines. CONCLUSIONS:
      Twice-daily dosing of FP is more effective than once-daily dosing, although the
      latter can maintain asthma control in most patients.

PMID- 10903486
TI  - TNF-alpha dysregulation in asthma: relationship to ongoing corticosteroidtherapy.
AB  - BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a major proinflammatory
      cytokine that is thought to be important in the pathogenesis of asthma. However,
      alterations in systemic regulation of this cytokine in asthma have not been
      examined in the context of corticosteroid therapy. OBJECTIVES: To examine the
      ability of peripheral blood mononuclear cells (PBMC) from three different groups
      of patients with asthma requiring varying amounts of inhaled corticosteroids
      (ICS) for clinical control, and to examine cells from age- and sex-matched
      nonasthmatic patients to produce TNF-alpha. DESIGN: All patients with asthma had
      a positive methacholine challenge test. 'High dose' ICS patients with asthma
      required ICS greater than or equal to 800 microg/day. 'Medium dose' patients with
      asthma were on less than or equal to 500 microg/day of ICS, whereas 'no ICS'
      patients with asthma had received no ICS for at least three months. Each patient
      with asthma was examined in parallel with an age- and sex-matched, nonasthmatic,
      nonatopic control subject. Cells were cultured (with or without the addition of
      potential stimulators phytohemagglutinin, lipopolysaccharide, formyl-methionine
      leucine-phenylalanine or antihuman CD3), and TNF-alpha production was assessed by
      ELISA. MAIN RESULTS: PBMC from both high dose ICS (n=8) and no ICS (n=11)
      patients with asthma produced more than twice the amount of TNF-alpha than cells
      from matched nonasthmatic control patients (P<0.01) when cultured alone or in the
      presence of each stimulus (P<0.05). In contrast, there was no significant
      difference in TNF-alpha production between medium dose ICS patients with asthma
      and control patients. A group of asymptomatic atopic patients (n=6) did not have
      an increased level of TNF-alpha production. CONCLUSIONS: Increases in TNF-a
      production within the PBMC compartment can be observed in both patients with
      asthma receiving high dose ICS and in a group of patients with mild asthma
      receiving no ICS therapy, but not in patients with asthma receiving a medium dose
      of ICS or atopic patients.

PMID- 10903487
TI  - Comparison of once- with twice-daily dosing of fluticasone propionate in mild and
      moderate asthma.
AB  - OBJECTIVES: Two 12-week, randomized, double-blind, parallel-group studies were
      performed to compare the efficacy and safety of once- and twice-daily dosing of
      fluticasone propionate (FP) in the treatment of mild to moderate asthma,
      considered to require the equivalent of either 200 or 500 microg of FP daily.
      PATIENTS AND METHODS: In study A, 461 patients with asthma received FP either 200
      microg once daily or 100 microg twice daily. In study B, 443 patients with asthma
      received FP, either 500 microg once daily or 250 microg twice daily. RESULTS: In
      both studies, regardless of the treatment regimen to which patients were randomly
      assigned, small improvements over baseline were observed in morning peak
      expiratory flows (PEF) and forced expiratory volume in 1 s (FEV1) following 12
      weeks of treatment. In study A, the mean morning PEF improved by 2.4% and 4.3%
      (once daily versus twice daily, P=0.008). In study B, the mean morning PEF
      improvement was 0.2% and 3.7% (once daily versus twice daily, P<0.001). For both
      studies, the increases observed in FEV1 were not significantly different between
      the two groups (P = not significant). The incidence of exacerbations of asthma
      and related events was 13% and 5%, respectively, in the patients with mild asthma
      for the once-daily group versus the twice-daily group; these exacerbations were
      12% and 10%, respectively, in patients with moderate asthma. Otherwise, the
      incidence and types of adverse events were comparable for the two treatment
      regimens. Although twice-daily dosing demonstrated small but statistically
      significant improvements over once-daily dosing, patients of both groups
      generally maintained a good level of asthma control on both regimens according to
      current treatment guidelines. CONCLUSIONS: Twice-daily dosing of FP is more
      effective than once-daily dosing, although the latter can maintain asthma control
      in most patients.

PMID- 10903488
TI  - Asthma management in the emergency department.
AB  - OBJECTIVES: To evaluate various aspects of the management of adult patients who
      present to the emergency department with acute exacerbations of asthma and who
      are discharged from the emergency department without hospital admission. Further,
      to compare the results with accepted management guidelines for the emergency
      department treatment of asthma. DESIGN: A retrospective chart collection and
      review until each site contributed 50 patients to the survey. SETTING: Three
      tertiary care hospitals in the Saskatoon Health District, Saskatoon,
      Saskatchewan. The study period was from July 1, 1997 to November 18, 1997.
      POPULATION: Patients aged 17 years or older, who were discharged from the
      emergency department with the diagnosis of asthma. METHODS: Data were collected
      on 130 patients from 147 emergency department visits. RESULTS: A number of
      important physical examination findings were frequently not documented. In
      contrast to management guidelines, peak expiratory flow rates (44%) and
      spirometry (1%) were not commonly used in patient assessments. Only 59% of
      patients received treatment in the emergency departments with inhaled or systemic
      corticosteroids. Furthermore, specific follow-up plans were infrequently
      documented in the emergency department charts (37%). CONCLUSIONS: Adherence with
      published Canadian guidelines for the emergency department management of acute
      asthma exacerbations was suboptimal. Corticosteroid use in the emergency
      department was significantly less than recommended. Increased emphasis on
      education and implementation of accepted asthma management guidelines is
      necessary.

PMID- 10903489
TI  - Neurogenic tumours of the mediastinum: a report of 60 cases.
AB  - OBJECTIVES: To analyze retrospectively 60 patients (13 infants and children, 47
      adults--21 men and 39 women) with mediastinal neurogenic tumours admitted to
      Ataturk Centre for Chest Disease and Chest Surgery, Ankara, Turkey between 1988
      and 1999. This comprised 21.2% of 283 patients who had surgical operations for
      all mediastinal masses during the same period. PATIENTS AND METHODS: The patients
      ranged from four to 67 years of age. Thirteen patients were younger than 15 years
      and 47 were 15 years of age or older. Medical records were reviewed for
      demographic data, clinical presentation, diagnostic investigations, operative
      procedures, and tumour location and invasion. Postoperative morbidity and
      mortality were noted as well as long term follow-up. The clinical investigations
      included chest x-ray and computed tomography of the thorax in all patients, and
      spinal magnetic resonance imaging and bronchoscopical examination in some.
      Clinical variables were compared. RESULTS: The tumours had the following
      characteristics: 42 (70%) were nerve sheath tumours; 15 (25%) were autonomic
      ganglion tumours; two (3.6%) were paragangliomas; and one (1.4%) was a malignant
      peripheral neuroectodermal tumour (Askin's tumour). Nerve cell tumours comprised
      the majority of tumours in infants and children (nine of 13, 69%), whereas the
      nerve sheath tumours were most frequent in adults (39 of 47, 83%). There were 48
      benign and 12 (20%) malignant tumours when all age groups were considered; the
      malignancy rate was 61.5% (eight of 13) in children and 8.5% (four of 47, P<0.05)
      in adults. All patients were operated via a posterolateral thoracotomy. Surgical
      resection of the tumour was complete in 56 of 60 patients (93.3%). Resection of
      malignant tumours was grossly incomplete in four cases (four of 12, 33.3%). All
      benign tumours were totally excised. There were two major complications
      (respiratory failure and pulmonary emboli) and 14 minor complications in the
      perioperative period. The mean follow-up period was five years and seven months.
      Tumours recurred in 5.3% (three of 56) of patients who had a complete resection
      initially. There were no late deaths related to benign tumours. CONCLUSIONS:
      Complete resection of tumours can be performed safely by a thoracotomy approach
      and is important for achieving satisfactory long term survival in most
      mediastinal neurogenic tumours.

PMID- 10903490
TI  - Revisiting "respiratory function in emphysema in relation to prognosis".
AB  - BACKGROUND: The 1956 paper by DV Bates, JMS Knott and RV Christie, "Respiratory
      function in emphysema in relation to prognosis" Quart J Med 1956;97:137-157 is
      largely reprinted with a commentary by the first author, Dr David Bates. Although
      the pathology of emphysema was well recognized at the time, the clinical
      diagnosis and assessment of its severity were known to be imprecise;
      physiological measurements assessing and following the clinical course had not
      been established. The study aimed to follow systematically a group of patients,
      selected by clinical criteria using standardized clinical and physiological
      techniques, over four years and correlate physiological and clinical changes in
      relation to prognosis and eventually to postmortem findings. Fifty-nine patients
      were recruited to an emphysema clinic at St Bartholomew's Hospital, London,
      England. Inclusion criteria were dyspnea without other causes and no cor
      pulmonale present. Patients' symptoms were assessed by a standardized
      questionnaire, and measurements were taken of lung volumes, maximal ventilatory
      volume, carbon monoxide diffusing capacity at rest, exercise and oxygen
      saturation by oximetry. During the four years of the study, 17 patients died
      (actuarial expected - four) and 13 presented with signs of pulmonary heart
      failure. All postmortem examinations (n=9) showed advanced emphysema. A seasonal
      variation in dyspnea was established (the period included the infamous 1952
      London smog). Four patients improved, and the remainder were unchanged or
      deteriorated. Close relationships were shown between dyspnea and function
      results, particularly for the diffusing capacity of lungs for carbon monoxide
      (DLCO). A comparison among a group of patients with chronic bronchitis without
      dyspnea showed that the DLCO discriminated between them. A loss of the normal
      increase in DLCO during exercise was shown in emphysema. IMPORTANCE: The study
      showed the value of standardized clinical and physiological techniques in
      following chronic obstructive pulmonary disease patients, and of separating the
      effects of airflow obstruction from impaired gas exchange function. Impaired gas
      exchange was shown to be important in influencing prognosis.

PMID- 10903491
TI  - Inspiratory capacity and exercise tolerance in chronic obstructive pulmonary
      disease.
AB  - During the past half-century, many studies have investigated the correlation of
      exercise tolerance to routine lung function in patients with obstructive
      pulmonary disease. In virtually all of these studies, the degree of airway
      obstruction was assessed in terms of forced expiratory volume in 1 s (FEV1) and
      forced vital capacity (FVC). Because in most studies only a weak correlation was
      found between exercise tolerance and degree of airway obstruction, it has been
      concluded that factors other than lung function impairment (eg, deconditioning
      and peripheral muscle dysfunction) play a predominant role in limiting exercise
      capacity in patients with chronic airway obstruction. Recent work, however,
      suggests that in patients with chronic obstructive pulmonary disease, the
      inspiratory capacity is a more powerful predictor of exercise tolerance than FEV1
      and FVC.

PMID- 10903492
TI  - Hydrogen ion gradients across the mitochondrial, endosomal and plasma membranes
      in bloodstream forms of trypanosoma brucei solving the three-compartment problem.
AB  - Conditions for the use of both [14C]methylamine and 5, 5-dimethyl[14C]oxa
      azolidine-2,4-dione (DMO) to measure the H+ concentration of intracellular
      compartments of monomorphic long thin bloodstream forms of Trypanosoma brucei
      were established. Neither probe was actively transported or bound to internal
      components of the cell and both probes equilibrated passively with a t1/2 close
      to 8 min. DMO was excluded from cells, while methylamine was accumulated but not
      metabolized. Solution of the three-compartment problem revealed that, when cells
      were respiring aerobically on glucose at an external pH of 7.5, the cytoplasmic
      pH was in the range 6.99-7.03, the pH of the mitochondrial matrix was 7.71-7.73,
      and the algebraic average pH of the various endosomal compartments was 5.19-5.50.
      Similar values were found when cells were respiring aerobically on glycerol.
      However, bloodstream forms of T. brucei could not maintain a constant internal H+
      concentration outside the external pH range 7.0-7.5, and no evidence for the
      presence of an H+/Na+ exchanger was found. Full motility and levels of pyruvate
      production were maintained as the external pH was raised as high as 9.5,
      suggesting that these cells tolerate significant internal alkalinisation.
      However, both motility and pyruvate production were severely inhibited under
      acidic conditions, and the cells deteriorated rapidly below an external pH of
      6.5. Physiologically, the plasma membrane of T. brucei had low permeability to H+
      and the internal pH was unaffected by changes in Deltapsip, which is dominated by
      the potassium diffusion potential. However, in the presence of FCCP, the internal
      pH fell rapidly about 0.5 pH unit and came into equilibrium with Deltapsip.
      Oligomycin abolished the mitochondrial pH gradient (DeltapHm) selectively,
      whereas chloroquine abolished only the endosomal pH gradient (DeltapHe). The pH
      gradient across the plasma membrane (DeltapHp) alone could be abolished by
      careful osmotic swelling of cells. The plasma membrane had an inwardly directed
      proton-motive force (DeltaPp) of -52 mV and an inwardly directed sodium-motive
      force (DeltaNp) of -149 mV, whereas the mitochondrial inner membrane had only an
      inwardly directed DeltaPm of -195 mV. The pH gradient across the endosomal
      membranes was not accompanied by an electrical gradient. Consequently, endosomal
      membranes had an algebraically average outwardly directed DeltaPl within the
      range + 89 to +110 mV, depending on the measurement method.

PMID- 10903493
TI  - Factors that determine the plasma-membrane potential in bloodstream forms of
      Trypanosoma brucei.
AB  - The plasma-membrane potential (Delta(psi)p) in bloodstream forms of Trypanosoma
      brucei was studied using several different radiolabelled probes: 86Rb+ and
      [14C]SCN- were used to report Delta(psi)p directly because they distribute in
      easily measured quantities across the plasma membrane only, and
      [3H]methyltriphenylphosphonium (MePh3P+) was used to report Delta(psi)p only when
      Delta(psi)m had been abolished with FCCP because it reports the algebraic sum of
      the two potentials when used alone. The unperturbed Delta(psi)p had a value of 
      82 mV and was found to be essentially identical with, and determined almost
      completely by, the potassium diffusion potential, as evidenced by: (a) the lack
      of effect of valinomycin on the value obtained under appropriate conditions when
      any of these probes were used; (b) the close agreement of this measured value
      with that predicted from the measured distribution of K+ across the plasma
      membrane (-76 mV); (c) the large effect of changes in the extracellular K+
      concentration by substitution with Na+ on Delta(psi)p together with the complete
      lack of effect of substitution of extracellular Na+ by the choline cation or
      substitution of extracellular Cl- by the gluconate anion on Delta(psi)p. The
      contribution to Delta(psi)p by electrogenic pumping of Na+/K+-ATPase was found to
      be small (of the order of 6 mV). H+ was not found to be pumped across the plasma
      membrane or to contribute to Delta(psi)p.

PMID- 10903494
TI  - Proteomic analysis of differential protein expression in primary hepatocytes
      induced by EGF, tumour necrosis factor alpha or the peroxisome proliferator
      nafenopin.
AB  - Peroxisome proliferators are nongenotoxic rodent-liver carcinogens that have been
      shown to cause both an induction of hepatocyte proliferation and a suppression of
      apoptosis. Both epidermal growth factor (EGF) and the peroxisome proliferator
      nafenopin induce DNA replication in primary rat hepatocyte cultures, but
      apparently through different signalling pathways. However, both EGF and nafenopin
      require tumour necrosis factor alpha (TNFalpha) signalling to induce DNA
      replication. By examining proteins isolated from rat primary hepatocyte cultures
      using two-dimensional gel electrophoresis and mass spectrometry, we found that
      proteins showing an altered expression pattern in response to nafenopin differed
      from those showing altered expression in response to EGF. However, many proteins
      showing altered expression upon stimulation with TNFalpha were common to both the
      EGF and nafenopin responses. These proteome profiling experiments contribute to a
      better understanding of the molecular mechanisms involved in the response to
      peroxisome proliferators. We found 32 proteins with altered expression upon
      stimulation with nafenopin, including muscarinic acetylcholine receptor 3,
      intermediate filament vimentin and the beta subunit of the ATP synthase. These
      nonperoxisomal protein targets offer insights into the mechanisms of peroxisome
      proliferator-induced carcinogenesis in rodents and provide opportunities to
      identify toxicological markers to facilitate early identification of nongenotoxic
      carcinogens.

PMID- 10903495
TI  - HNF-4 plays a pivotal role in the liver-specific transcription of the chipmunk HP
      25 gene.
AB  - The gene for chipmunk hibernation-specific protein HP-25 is expressed
      specifically in the liver. To understand the transcriptional regulation of HP-25
      gene expression, we isolated its genomic clones, and characterized its structural
      organization and 5' flanking region. The gene spans approximately 7 kb and
      consists of three exons. The transcription start site, as determined by primer
      extension analysis, is located at 113 bp upstream of the translation initiation
      codon. Transient transfection studies in HepG2 cells revealed that the 80 bp 5'
      flanking sequence was sufficient for the liver-specific promoter activity. In a
      gel retardation assay using HepG2 nuclear extracts, the 5' flanking sequence from
      -74 to -46 showed a shifted band. All cDNA clones isolated by a yeast one-hybrid
      system for a protein capable of binding to this 5' flanking sequence encoded HNF
      4. HNF-4 synthesized in vitro bound to this sequence in a gel retardation assay.
      Furthermore, supershift assays with anti-(HNF-4) Ig confirmed that the protein in
      HepG2 or chipmunk liver nuclear extracts that bound to this sequence was HNF-4.
      When transfected into HeLa cells, HNF-4 transactivated transcription from the HP
      25 gene promoter, and mutation of the HNF-4 binding site abolished
      transactivation by HNF-4, indicating that HNF-4 plays an important role in HP-25
      gene expression.

PMID- 10903496
TI  - Conotoxin TVIIA, a novel peptide from the venom of Conus tulipa 1. Isolation,
      characterization and chemical synthesis.
AB  - A novel conotoxin belonging to the 'four-loop' structural class has been isolated
      from the venom of the piscivorous cone snail Conus tulipa. It was identified
      using a chemical-directed strategy based largely on mass spectrometric
      techniques. The new toxin, conotoxin TVIIA, consists of 30 amino-acid residues
      and contains three disulfide bonds. The amino-acid sequence was determined by
      Edman analysis as SCSGRDSRCOOVCCMGLMCSRGKCVSIYGE where O = 4-transL
      hydroxyproline. Two under-hydroxylated analogues, [Pro10]TVIIA and
      [Pro10,11]TVIIA, were also identified in the venom of C. tulipa. The sequences of
      TVIIA and [Pro10]TVIIA were further verified by chemical synthesis and coelution
      studies with native material. Conotoxin TVIIA has a six cysteine/four-loop
      structural framework common to many peptides from Conus venoms including the
      omega-, delta- and kappa-conotoxins. However, TVIIA displays little sequence
      homology with these well-characterized pharmacological classes of peptides, but
      displays striking sequence homology with conotoxin GS, a peptide from Conus
      geographus that blocks skeletal muscle sodium channels. These new toxins and GS
      share several biochemical features and represent a distinct subgroup of the four
      loop conotoxins.

PMID- 10903497
TI  - Conotoxin TVIIA, a novel peptide from the venom of Conus tulipa 2. Three
      dimensional solution structure.
AB  - The three-dimensional solution structure of conotoxin TVIIA, a 30-residue
      polypeptide from the venom of the piscivorous cone snail Conus tulipa, has been
      determined using 2D 1H NMR spectroscopy. TVIIA contains six cysteine residues
      which form a 'four-loop' structural framework common to many peptides from Conus
      venoms including the omega-, delta-, kappa-, and muO-conotoxins. However, TVIIA
      does not belong to these well-characterized pharmacological classes of
      conotoxins, but displays high sequence identity with conotoxin GS, a muscle
      sodium channel blocker from Conus geographus. Structure calculations were based
      on 562 interproton distance restraints inferred from NOE data, together with 18
      backbone and nine side-chain torsion angle restraints derived from spin-spin
      coupling constants. The final family of 20 structures had mean pairwise rms
      differences over residues 2-27 of 0.18+/-0.05 A for the backbone atoms and 1.39+/
      0.33 A for all heavy atoms. The structure consists of a triple-stranded,
      antiparallel beta sheet with +2x, -1 topology (residues 7-9, 16-20 and 23-27) and
      several beta turns. The core of the molecule is formed by three disulfide bonds
      which form a cystine knot motif common to many toxic and inhibitory polypeptides.
      The global fold, molecular shape and distribution of amino-acid sidechains in
      TVIIA is similar to that previously reported for conotoxin GS, and comparison
      with other four-loop conotoxin structures provides further indication that TVIIA
      and GS represent a new and distinct subgroup of this structural family. The
      structure of TVIIA determined in this study provides the basis for determining a
      structure-activity relationship for these molecules and their interaction with
      target receptors.

PMID- 10903498
TI  - Expression of gelatinases A and B in the ovary of the medaka fish Oryzias
      latipes.
AB  - We cloned cDNAs for gelatinase A and gelatinase B from an ovary cDNA library of
      the medaka fish Oryzias latipes. The gelatinase A clone encodes a protein of 657
      amino acids, whereas the gelatinase B clone encodes a protein of 690 amino acids.
      Gelatinase A mRNA was expressed in the testis, ovary, intestine, heart, spleen
      and kidney of the animal. In contrast, gelatinase B mRNA was detected in the
      ovary. Localization of the respective mRNAs in the ovary was examined using in
      situ hybridization. Gelatinase A mRNA was found only in the oocytes of small and
      middle-sized follicles. In contrast, gelatinase B was expressed exclusively in
      follicular tissues that had ovulated. In situ zymographic analysis revealed that
      gelatinolytic activity, presumably due to matrix metalloproteinase activity, was
      detectable in the areas surrounding small and middle-sized follicles,
      interstitial stromal tissues and the cytoplasm of oocytes. Using extracts of the
      whole ovary and of ovulated oocytes, several gelatin-degrading enzymes, which
      probably represent the intermediate and active forms of medaka fish gelatinase A
      and gelatinase B, were detected by gelatin zymographic analysis. These results
      clearly indicate that gelatinase A and gelatinase B play a discrete role in the
      ovary of this lower vertebrate animal.

PMID- 10903499
TI  - Genetic organization of A chain and B chain of beta-bungarotoxin from Taiwan
      banded krait (Bungarus multicinctus). A chain genes and B chain genes do not
      share a common origin.
AB  - beta-Bungarotoxin, the main presynaptic neurotoxin purified from the venom of
      Bungarus multicinctus, consists of two dissimilar polypeptide chains, the A chain
      and the B chain, cross-linked by an interchain disulfide bond. In this study, A
      and B chain genes isolated from the liver of B. multicinctus encoded the A and B
      chain precursors, respectively. Analyses of the coding regions of the A and B
      chain genes revealed that both consist of three exons and two introns. The
      sequences of all exon/intron junctions agree with the GT/AG rule. However,
      sequence alignment and phylogenetic analysis did not support that the evolution
      of A and B chain genes are closely related. Comparative analysis of A chain genes
      with Viperinae and Crotalinae phospholipase A2 genes indicated that genetic
      divergence of the A chain and phospholipase A2s was in accordance with their
      family. Moreover, evolutionary divergence of the intron and exon regions of the A
      chain, as observed for phospholipase A2 genes, was not consistent. Noticeably,
      the transcription of A and B chain genes may be regulated under different
      transcription factors as revealed by analyses of their promoter sequences. In
      terms of the finding that A and B chains are encoded separately by different
      genes, this strongly supports the view that the intact beta-bungarotoxin
      molecules should be derived from the pairing of A and B chains after their mRNAs
      are translated.

PMID- 10903500
TI  - Expression of immediate early gene pip92 during anisomycin-induced cell death is
      mediated by the JNK- and p38-dependent activation of Elk1.
AB  - We report here that immediate early gene pip92 is expressed during anisomycin
      induced cell death in fibroblast NIH3T3 cells. To determine the mechanism by
      which this occurs and to identify downstream signaling pathways, we investigated
      the induction of the pip92 promoter. The activation of pip92 by anisomycin is
      mediated by the activation of MAP kinases, such as JNK and p38 kinase, but not
      ERK. Deletion analysis of the pip92 promoter indicated that pip92 activation
      occurs primarily within the region containing a serum response element (SRE).
      Further analysis of the SRE using a heterologous thymidine kinase promoter showed
      that both an Ets and CArG-like site are required for anisomycin-induced pip92
      expression. Elk1, which binds to the Ets site, was phosphorylated by the JNK- and
      p38-dependent pathways and the phosphorylation of Elk1-GAL4 fusion proteins by
      these pathways was sufficient for the transactivation. Overall, this study
      suggested that different MAPK pathways are involved in the expression of
      immediate early gene pip92 by growth factors and environmental stresses.

PMID- 10903501
TI  - Regulation of the expression of human ferrochelatase by intracellular iron
      levels.
AB  - Mammalian ferrochelatase, the terminal enzyme of the heme biosynthetic pathway,
      catalyzes the insertion of a ferrous ion into protoporphyrin and contains a
      labile [2Fe-2S] cluster center at the C-terminus. To clarify the roles of the
      iron-sulfur cluster in the expression of mammalian ferrochelatase, enzyme
      activity in human erythroleukemia K562 cells under iron-depleted conditions was
      examined. Treatment of cells with an iron chelator, desferrioxamine, resulted in
      a decrease in enzyme activity, in a dose- and time-dependent manner. Heme content
      decreased during desferrioxamine treatment of the cells. Addition of ferric ion
      nitrilotriacetate [Fe (III)NTA] to desferrioxamine-containing cultures led to
      restoration of the reduction in the enzyme activity. While RNA blots showed that
      the amount of ferrochelatase mRNA remained unchanged during these treatments, the
      amount of ferrochelatase decreased with a concomitant decrease in enzyme
      activity. When full-length human ferrochelatase was expressed in Cos7 cells, the
      activity was found mainly in the mitochondria and was decreased markedly by
      treatment with desferrioxamine. The activity in Cos7 cells expressing human
      ferrochelatase in cytoplasm decreased with desferrioxamine, but to a lesser
      extent. When Escherichia coli ferrochelatase, which lacks the iron-sulfur
      cluster, was expressed in Cos7 cells, the activity did not change following any
      treatment. Conversely, the addition of Fe (III)NTA to the culture of K562 and
      Cos7 cells led to an increase in ferrochelatase activity. These results indicate
      that the expression of mammalian ferrochelatase is regulated by intracellular
      iron levels, via the iron-sulfur cluster center at the C-terminus, and this
      contributes to the regulation of the biosynthesis of heme at the terminal step.

PMID- 10903502
TI  - Fibrinogen interactions with ICAM-1 (CD54) regulate endothelial cell survival.
AB  - We tested hypothesis that the interaction of fibrinogen (Fg) with intercellular
      adhesion molecule 1 (ICAM-1) mediates cellular adhesion and cell proliferation.
      Our results demonstrate that Fg : ICAM-1 ligation mediates endothelial cell
      survival and has an anti-apoptotic effect via activation of the MAP kinase
      pathway. Fg : ICAM-1 ligation in endothelial cells treated with tumor necrosis
      factor (TNF)alpha resulted in the hyperphosphorylation of extracellular signal
      regulated kinase (ERK)-1/2 (eightfold to 10-fold) at 5-30 min. The specificity of
      ERK-1/2 phosphorylation was verified using the recognition peptides Fg-gamma-(117
      133) and ICAM-1(8-22). ERK-1/2 hyperphosphorylation was dependent on intact
      cytoskeleton, as treatment with cytochalasin B and nocodazole blocked this
      activity. The attachment of TNFalpha-treated endothelial cells to fibrinogen or
      Fg-gamma-(117-133) resulted in cell survival, as assessed by an annexin V binding
      assay. ICAM-1(8-22) blocked the survival process. The MEK-1 inhibitor PD 98059
      blocked ERK-1/2 phosphorylation, and treatment of endothelial cells with PD 98059
      resulted in apoptosis even upon Fg : ICAM-1 ligation. Cells transfected with
      dominant-negative ERK-1/2 underwent apoptosis upon Fg : ICAM-1 ligation. Cell
      survival factor A1 was specifically upregulated upon adhesion of TNFalpha
      stimulated endothelial cells to Fg. A1 expression was blocked by ICAM-1(8-22) and
      PD 98059. The Fg : ICAM-1 endothelial cell survival pathway appears to be
      mediated via the activation and upregulation of ERK-1/2 and A1.

PMID- 10903503
TI  - alpha-crystallin prevents irreversible protein denaturation and acts
      cooperatively with other heat-shock proteins to renature the stabilized partially
      denatured protein in an ATP-dependent manner.
AB  - alpha-Crystallin, a major lens protein of approximately 800 kDa with subunits of
      approximately 20 kDa has previously been shown to act as a chaperone protecting
      other proteins from stress-induced aggregation. Here it is demonstrated that
      alpha-crystallin can bind to partially denatured enzymes at 42-43 degrees C and
      prevent their irreversible aggregation, but cannot prevent loss of enzyme
      activity. However, the alpha-crystallin-bound enzymes regain activity on
      interaction with other chaperones. The data indicate that the re-activated
      enzymes are no longer associated with the alpha-crystallin, and ATP is required
      for re-activation. When inactive luciferase bound to alpha-crystallin was treated
      with reticulocyte lysate, a rich source of chaperones, up to 60% of the original
      luciferase activity could be recovered. Somewhat less re-activation was observed
      when the alpha-crystallin-bound enzyme was treated with heat-shock protein
      (HSP)70, HSP40, HSP60 and an ATP-generating system. Similar results were also
      obtained with citrate synthase. The overall results suggest that alpha-crystallin
      acts to stabilize denaturing proteins so that they can later be re-activated by
      other chaperones.

PMID- 10903504
TI  - Identification of foetal brain proteins by two-dimensional gel electrophoresis
      and mass spectrometry comparison of samples from individuals with or without
      chromosome 21 trisomy.
AB  - Protein expression in foetal brain with or without chromosome 21 trisomy (Down's
      syndrome) was analyzed by two-dimensional gel electrophoresis and mass
      spectrometry. Data generated by in-gel digestion and matrix-assisted laser
      desorption/ionization mass spectrometry allowed identification of 40 proteins.
      Most of these are common to syndrome and healthy subjects and represent different
      types of protein. However, a few proteins, identified as truncated structural
      proteins (tubulin, actin), were present in part of the trisomy samples but absent
      from the controls. This is interpreted to indicate increased proteolysis in the
      syndrome samples but could also reflect some altered expression or processing.
      Independent of the apparently increased proteolysis in the syndrome samples, and
      in spite of the use of total brain tissues, the results show that two-dimensional
      protein separation patterns are largely similar between the syndrome and control
      samples upon silver-staining, but that differences associated with structural
      components can be detected and identified.

PMID- 10903505
TI  - Annexin V relocates to the platelet cytoskeleton upon activation and binds to a
      specific isoform of actin.
AB  - We have previously reported that stimulation of platelets causes a relocation of
      annexin V to the cytoplasmic side of the plasma membrane where it associates with
      actin. This study examined the association of annexin V with the platelet
      cytoskeleton and its binding to actin, following both physiological activation
      with thrombin and Ca2+ -ionophore activation. The time-dependence of annexin V
      incorporation into the detergent-extracted cytoskeleton following activation with
      thrombin was also measured. Although calcium from the intracellular stores was
      enough to relocate intracellular annexin V to the cytoskeleton, this relocation
      was further enhanced by influx of extracellular calcium. The association of
      annexin V with the cytoskeleton was found to be unaffected by the action of
      cytochalasin E, however, annexin V was solubilized when DNase I was used to
      depolymerize the membrane cytoskeleton, and spontaneously re-associated with the
      actin filaments when re-polymerization was induced in vitro. Using a bifunctional
      crosslinking reagent we have identified an 85-kDa complex in both membrane and
      cytoskeleton fractions containing annexin V and actin. Direct binding to actin
      filaments was only observed in high [Ca2+], however, inclusion of an extract from
      thrombin-stimulated platelets lowered the [Ca2+] requirement for the binding of
      annexin V to F-actin to physiological levels. We also show that GST-annexin V
      mimics the physiological binding of annexin V to membranes, and that this GST
      annexin V binds directly to a specific isoform of actin. Immunoprecipitation
      using antibodies against annexin V copurify annexin V and gamma- but not beta
      actin from activated platelets. This is the first report of a possible
      preferential binding of annexin V to a specific isoform of actin, namely gamma
      actin. The results of this study suggest a model in which annexin V that
      relocates to the plasma membrane and binds to gamma-actin in an activation
      dependent manner forms a strong association with the platelet cytoskeleton.

PMID- 10903506
TI  - Organization-dependent effects of toxic bivalent ions microtubule assembly and
      glycolysis.
AB  - The effects of bivalent ions on tubulin dynamics and the upper phase of
      glycolysis were investigated at different organization levels in vitro. Cu2+,
      Cd2+, Hg2+ and CrO4(2-) inhibit the tubulin polymerization at an IC50 of 14-24
      microM with high cooperativity and also induce microtubule disassembly. The
      apparent binding constants of the ions to tubulin, estimated by fluorescence
      quenching, vary between 6 and 28 microM. BIAcore measurements for tubulin-tubulin
      interaction suggest that the presence of Cu2+ affects neither koff nor kon, but
      the amount of the bound tubulin. While the inhibitory effect of Cu2+ on tubulin
      polymerization is partially abolished by cross-linking of microtubules with
      substoichiometric amounts of phosphofructokinase or decoration of tubules with
      cytosolic proteins, in the presence of kinase but not with cytosolic proteins the
      tubules are resistant to CrO4(2-). No inhibitory effect of Cu2+ or CrO4(2-) on
      microtubule assembly was detected in the MAP-containing cytosolic fraction.
      Electron microscopy revealed that tubules assembled in the presence of Cu2+ or
      CrO4(2-) ions contain aggregates of thread-like oligomers that are less
      conspicuous in the presence of cytosolic proteins. Cu2+, Cd2+, and Hg2+ inhibit
      the glycolytic flux in the cytosolic fraction characterized at equilibrium by an
      IC50 of 10-14 microM with high cooperativity. Tubulin diminishes the inhibitory
      effect of the cations. These data indicate that the responses elicited by the
      bivalent ions are highly dependent on the supramolecular organization of the
      systems.

PMID- 10903507
TI  - Homodimeric reverse transcriptases from rous sarcoma virus mutated within the
      polymerase or RNase H active site of one subunit are active.
AB  - Heterodimeric reverse transcriptase (RT) alphabeta from Rous sarcoma virus (RSV)
      possesses an asymmetric subunit organization with the polymerase and RNase H
      active sites localized in the alpha subunit. To determine whether homodimeric RSV
      RTs alpha (63 kDa) or beta (95 kDa) assume alpha subunit organization similar to
      that of the heterodimer, an essential aspartic acid residue was mutated in the
      active site of either the polymerase (Asp181 > Asn) or the RNase H (Asp505 >
      Asn). Homodimeric alpha or beta RT consisting of one wild-type and one mutated
      subunit exhibit polymerase or RNase H activity, respectively, whereas the
      corresponding doubly mutated enzymes are inactive, indicating that the catalytic
      sites of the polymerase and RNase H domains are formed by only one subunit of the
      homodimer.

PMID- 10903508
TI  - Divalent metal cation binding properties of human prothymosin alpha.
AB  - The divalent cation binding properties of human prothymosin alpha, an abundant
      nuclear protein involved in cell proliferation, were evaluated. By using
      prothymosin alpha retardation on a weak cation chelating resin charged with
      various divalent cations, specific binding of Zn2+ ions by prothymosin alpha was
      observed. This finding was further confirmed by the equilibrium dialysis analysis
      which demonstrated that, within the micromolar range of Zn2+ concentrations,
      prothymosin alpha could bind up to three zinc ions in the presence of 100 mM NaCl
      and up to 13 zinc ions in the absence of NaCl. Equilibrium dialysis analysis also
      revealed that prothymosin alpha could bind Ca2+, although the parameters of Ca2+
      binding by prothymosin alpha were less pronounced than those of Zn2+ binding in
      terms of the number of metal ions bound, the KD values, and the resistance of the
      bound metal ions to 100 mM NaCl. The effects of Zn2+ and Ca2+ on the interaction
      of prothymosin alpha with its putative partners, Rev of HIV type 1 and histone
      H1, were examined. We demonstrated that Rev binds prothymosin alpha, and that
      prothymosin alpha binding to Rev but not to histone H1 was significantly enhanced
      in the presence of zinc and calcium ions. Our data suggest that the modes of
      prothymosin alpha interaction with Rev and histone H1 are distinct and that the
      observed zinc and calcium-binding properties of prothymosin alpha might be
      functionally relevant.

PMID- 10903510
TI  - Purification and partial characterization of the hydroxylase component of the
      methanesulfonic acid mono-oxygenase from methylosulfonomonas methylovora strain
      M2.
AB  - The reductase enzyme and the hydroxylase enzyme of the three-component
      methanesulfonic acid mono-oxygenase (MSAMO) from Methylosulfonomonas methylovora
      were purified. Purification of the reductase from M. methylovora using a range of
      chromatographic techniques was accompanied by complete loss of activity.
      Expression of the reductase as a glutathionine S-transferase fusion protein in
      Escherichia coli cells was successful as judged from the size of the polypeptide
      band obtained on induction with isopropyl thio-beta-D-galactoside. Subsequent
      affinity purification of the fusion protein, however, led to a protein extract
      containing only glutathionine S-transferase protein, indicating that the fusion
      protein was unstable in vitro. The hydroxylase component of the MSAMO was
      purified from M. methylovora to near electrophoretic homogeneity using Q
      Sepharose, hydroxyapatite and Mono Q chromatography. SDS/PAGE of the purified
      hydroxylase showed a single band at approximately 43.7 kDa for the alpha-subunit
      and a double band at approximately 23 kDa for the beta-subunit. MS scans obtained
      with matrix-assisted laser desorption/ionization and electrospray ionization
      showed single peaks for both subunits, with a mass of 48 145.4 Da for alpha, 20
      479.1 Da for beta, and 68 624.5 for the alphabeta-monomer. Gel filtration
      revealed a mass of 209 kDa, suggesting an alpha3beta3 structure for the native
      enzyme. Purified hydroxylase enzyme exhibited absorbance maxima at 330 nm, 460 nm
      and 570 nm, indicating the presence of iron-sulfur centres. The protein
      preparations contained 1 mol sulfide and 3-4 mol iron per mol alphabeta-monomer.
      Chromium, cobalt, copper, lead, nickel, molybdenum, tungsten and vanadium were
      not found. Flavins were also absent. Antibodies raised against the native
      hydroxylase enzyme cross-reacted with cell-free extract from M. methylovora cells
      grown with methanesulfonate, but not with extract from cells grown with methanol,
      confirming that MSAMO was specifically induced during growth on methanesulfonate.

PMID- 10903509
TI  - Recombinant glycodelin carrying the same type of glycan structures as
      contraceptive glycodelin-A can be produced in human kidney 293 cells but not in
      chinese hamster ovary cells.
AB  - We have produced human recombinant glycodelin in human kidney 293 cells and in
      Chinese hamster ovary (CHO) cells. Structural analyses by lectin immunoassays and
      fast atom bombardment mass spectrometry showed that recombinant human glycodelin
      produced in CHO cells contains only typical CHO-type glycans and is devoid of any
      of the N, N'-diacetyllactosediamine (lacdiNAc)-based chains previously identified
      in glycodelin-A (GdA). By contrast, human kidney 293 cells produced recombinant
      glycodelin with the same type of carbohydrate structures as GdA. The presence of
      a beta1-->4-N-acetylgalactosaminyltransferase functioning in the synthesis of
      lacdiNAc-based glycans in human kidney 293 cells is concluded to be the cause of
      the occurrence of lacdiNAc-based glycans on glycodelin produced in these cells.
      Furthermore, human kidney 293 cells were found to be particularly suited for the
      production of recombinant glycodelin when they were cultured in high glucose
      media. Lowering the glucose concentration and the addition of glucosamine
      resulted in higher relative amounts of oligomannosidic-type glycans and complex
      glycans with truncated antennae. Human glycodelin is an attractive candidate for
      the development of a contraceptive agent, and this study gives valuable
      information for selecting the proper expression system and cell culture
      conditions for the production of a correctly glycosylated recombinant form.

PMID- 10903511
TI  - Structural investigations of the hemoglobin of the cyanobacterium Synechocystis
      PCC6803 reveal a unique distal heme pocket.
AB  - A putative hemoglobin (Hb) gene, related to those previously characterized in the
      green alga Chlamydomonas eugametos, the ciliated protozoan Paramecium caudatum,
      the cyanobacterium Nostoc commune and the bacterium Mycobacterium tuberculosis,
      was recently discovered in the complete genome sequence of the cyanobacterium
      Synechocystis PCC 6803. In this paper, we report the purification of
      Synechocystis Hb and describe some of its salient biochemical and spectroscopic
      properties. We show that the recombinant protein contains Fe-protoporphyrin IX
      and forms a very stable complex with oxygen. The oxygen dissociation rate
      measured, 0.011 s(-1), is among the smallest known and is four orders of
      magnitude smaller than the rate measured for N. commune Hb, which suggests
      functional differences between these Hbs. Optical and resonance Raman
      spectroscopic study of the structure of the heme pocket of Synechocystis Hb
      reveals that the heme is 6-coordinate and low-spin in both ferric and ferrous
      forms in the pH range 5.5-10.5. We present evidence that His46, predicted to
      occupy the helical position E10 based on amino-acid sequence comparison, is
      involved in the formation of the ferric and ferrous 6-coordinate low-spin
      structures. The analysis of the His46Ala mutant shows that the ferrous form is 5
      coordinate and high-spin and the ferric form contains a 6-coordinate high-spin
      component in which the sixth ligand is most probably a water molecule. We
      conclude that the heme pocket of the wild type Synechocystis Hb has a unique
      structure that requires a histidine residue at the E10 position for the formation
      of its native structure.

PMID- 10903512
TI  - In vitro hyperprocessing of Drosophila tRNAs by the catalytic RNA of RNase P the
      cloverleaf structure of tRNA is not always stable?
AB  - We have previously reported that the catalytic RNA subunit of RNase P of
      Escherichia coli (M1 RNA) cleaves Drosophila initiator methionine tRNA
      (tRNA(Met)i) within the mature tRNA sequence to produce specific fragments. This
      cleavage was dependent on the occurrence of an altered conformation of the tRNA
      substrate. We call this further cleavage hyperprocessing. In the present paper,
      to search for another tRNA that can be hyperprocessed in vitro, we used total
      mature tRNAs from Drosophila as substrates for the in vitro M1 RNA reaction. We
      found that some tRNAs can be hyperprocessed by M1 RNA and that two such tRNAs are
      an alanine tRNA and a histidine tRNA. Using mutant substrates of these tRNAs, we
      also show that the hyperprocessing by M1 RNA is dependent on the occurrence of
      altered conformations of these tRNAs. The altered conformations were very similar
      to that of tRNA(Met)i. We show here that M1 RNA can be used as a powerful tool to
      detect the alternative conformation of tRNAs. The relationship between these
      hyperprocessing reactions and stability of the tRNA structure will also be
      discussed.

PMID- 10903514
TI  - Interaction of the neurotoxic and nontoxic secretory phospholipases A2 with the
      crotoxin inhibitor from Crotalus serum.
AB  - Crotalus durissus terrificus snakes possess a protein in their blood, named
      crotoxin inhibitor from Crotalus serum (CICS), which protects them against
      crotoxin, the main toxin of their venom. CICS neutralizes the lethal potency of
      crotoxin and inhibits its phospholipase A2 (PLA2) activity. The aim of the
      present study is to investigate the specificity of CICS towards snake venom
      neurotoxic PLA2s (beta-neurotoxins) and nontoxic mammalian PLA2s. This
      investigation shows that CICS does not affect the enzymatic activity of
      pancreatic and nonpancreatic PLA2s, bee venom PLA2 and Elapidae beta-neurotoxins
      but strongly inhibits the PLA2 activity of Viperidae beta-neurotoxins. Surface
      plasmon resonance and PAGE studies further demonstrated that CICS makes complexes
      with monomeric and multimeric Viperidae beta-neurotoxins but does not interact
      with nontoxic PLA2s. In the case of dimeric beta-neurotoxins from Viperidae
      venoms (crotoxin, Mojave toxin and CbICbII), which are made by the noncovalent
      association of a PLA2 with a nonenzymatic subunit, CICS does not react with the
      noncatalytic subunit, instead it binds tightly to the PLA2 subunit and induces
      the dissociation of the heterocomplex. In vitro assays performed with Torpedo
      synaptosomes showed a protective action of CICS against Viperidae beta
      neurotoxins but not against other PLA2 neurotoxins, on primary and evoked
      liberation of acetylcholine. In conclusion, CICS is a specific PLA2 inhibitor of
      the beta-neurotoxins from the Viperidae family.

PMID- 10903513
TI  - Valyl-tRNA synthetase from Escherichia coli MALDI-MS identification of the
      binding sites for L-valine or for noncognate amino acids upon qualitative
      comparative labeling with reactive amino-acid analogs.
AB  - Bromomethyl ketone derivatives of L-valine (VBMK), L-isoleucine (IBMK), L
      norleucine (NleBMK) and L-phenylalanine (FBMK) were synthesized. These reagents
      were used for qualitative comparative labeling of Escherichia coli valyl-tRNA
      synthetase (ValRS), an enzyme with Val/Ile editing activity, in order to identify
      the binding sites for L-valine or noncognate amino acids. Labeling of E. coli
      ValRS with the substrate analog valyl-bromomethyl ketone (VBMK) resulted in a
      complete loss of valine-dependent isotopic [32P]PPi-ATP exchange activity. L
      Valine protected the enzyme against inactivation. Noncognate amino acids analogs
      isoleucyl-, norleucyl- and phenylalanyl-bromomethyl ketones (IBMK, NleBMK and
      FBMK) were also capable of abolishing the activity of ValRS, FBMK being less
      efficient in inactivating the synthetase. Matrix-assisted laser desorption
      ionization mass spectrometry designated cysteines 424 and 829 as the target
      residues of the substrate analog VBMK on E. coli ValRS, whereas, altogether,
      IBMK, NleBMK and FBMK labeled His266, Cys275, His282, His433 and Cys829, of which
      Cys275, His282 and His433 were labeled in common by all three noncognate amino
      acid-derived bromomethyl ketones. With the exception of Cys829, which was most
      likely unspecifically labeled, the amino-acid residues labeled by the reagents
      derived from noncognate amino acids were distributed between two fragments 259
      291 and 419-434 in the primary structure of E. coli ValRS. In fragment 419-434,
      Cys424 was specifically labeled by the substrate analog VBMK, while His433 was
      labeled in common by all the used bromomethyl ketone derivatives of noncognate
      amino acids, suggesting that the synthetic site where aminoacyl adenylate
      formation takes place on E. coli ValRS is built up of two subsites. One subsite
      containing Cys424 might represent the catalytic locus of the active center where
      specific L-valine activation takes place. The second subsite containing His433
      might represent the binding site for noncognate amino acids. The fact that Cys275
      and His282, fragment 259-291, were labeled by IBMK, NleBMK and FBMK, but not by
      the substrate analog VBMK, suggests that these residues might be located at or
      near the editing site of E. coli ValRS. Comparison of fragment 259-291 with all
      the available ValRS amino-acid sequences revealed that His282 is strictly
      conserved, with the exception of its replacement by a glycine in a subgroup
      corresponding to the archaebacteria. Because a nucleophile is needed in the
      editing site to achieve hydrolysis of an undesired product at the level of the
      carbonyl group thereof, it is proposed that the conserved His282 of E. coli ValRS
      is involved in editing.

PMID- 10903515
TI  - Diazaborine resistance in yeast involves the efflux pumps Ycf1p and Flr1p and is
      enhanced by a gain-of-function allele of gene YAP1.
AB  - We have found that YAP1-mediated diazaborine resistance in the yeast
      Saccharomyces cerevisiae requires two efflux pumps, i.e. the major-facilitator
      superfamily transporter Flr1p, which is located in the cytoplasmic membrane and
      the ATP-binding-cassette transporter Ycf1p which is present in the vacuolar
      membrane. Both these transporters are known to be under the control of the
      transcriptional transactivator Yap1p which explains our earlier finding that
      overexpression of YAP1 mediates diazaborine resistance. Overexpression of YAP1 in
      a Deltaflr1Deltaycf1 double disruptant strain does not mediate any diazaborine
      resistance, showing that these pumps are the only ones involved in detoxification
      of this drug. We also found a new mechanism of diazaborine resistance which is
      caused by an allelic form of YAP1, designated YAP1-11. This allele of YAP1
      carries a mutation that leads to a C620F exchange in the C-terminal cysteine-rich
      domain region and is the first mutant of YAP1 that was isolated by a conventional
      genetic screen for drug resistance. The protein encoded by the gain-of-function
      allele may transactivate by a different mechanism from the wild-type protein when
      overexpressed because it does not enhance YCF1 mRNA and still mediates
      diazaborine resistance in a Deltaflr1Deltaycf1 background.

PMID- 10903516
TI  - Role of glutathione in the formation of the active form of the oxygen sensor FNR
      ([4Fe-4S].FNR) and in the control of FNR function.
AB  - The oxygen sensor regulator FNR (fumarate nitrate reductase regulator) of
      Escherichia coli is known to be inactivated by O2 as the result of conversion of
      a [4Fe-4S] cluster of the protein into a [2Fe-2S] cluster. Further incubation
      with O2 causes loss of the [2Fe-2S] cluster and production of apoFNR. The
      reactions involved in cluster assembly and reductive activation of apoFNR
      isolated under anaerobic or aerobic conditions were studied in vivo and in vitro.
      In a gshA mutant of E. coli that was completely devoid of glutathione, the O2
      tension for the regulatory switch for FNR-dependent gene regulation was decreased
      by a factor of 4-5 compared with the wild-type, suggesting a role for glutathione
      in FNR function. In isolated apoFNR, glutathione could be used as the reducing
      agent for HS- formation required for [4Fe-4S] assembly by cysteine desulfurase
      (NifS), and for the reduction of cysteine ligands of the FeS cluster in FNR. Air
      inactivated FNR (apoFNR without FeS) could be reconstituted to [4Fe-4S].FNR by
      the same reaction as used for apoFNR isolated under anaerobic conditions. The in
      vivo effects of glutathione on FNR function and the role of glutathione in the
      formation of active [4Fe-4S].FNR in vitro suggest an important role for
      glutathione in the de novo assembly of FNR and in the reductive activation of air
      oxidized FNR under anaerobic conditions.

PMID- 10903517
TI  - Generation of catalytically active 6-phosphofructokinase from Saccharomyces
      cerevisiae in a cell-free system.
AB  - PFK1 and PFK2 coding for the subunits of 6-phosphofructokinase from Saccharomyces
      cerevisiae were cloned into plasmids suitable for runoff transcription. In vitro
      translation products of both kinds of subunit were obtained using rabbit
      reticulocyte lysate as the synthesis and folding system. They were monitored by
      chemiluminescent Western-blot analysis. Folding and assembly of the alpha-subunit
      and beta-subunit of 6-phosphofructokinase were found to occur in the cell-free
      system resulting in an enzymatically active protein. The in vitro generated
      enzyme exhibits a folding state that is similar to that of the heterooctameric
      form of 6-phosphofructokinase in the presence of fructose 6-phosphate, ATP and
      ammonium sulfate, as demonstrated by size-exclusion HPLC followed by ELISA.

PMID- 10903518
TI  - Differential degradation of Escherichia coli sigma32 and Bradyrhizobium japonicum
      RpoH factors by the FtsH protease.
AB  - The Escherichia coli heat shock sigma factor sigma32 (RpoH) is rapidly degraded
      under non-stress conditions. The integrity of the DnaK chaperone machinery and
      the ATP-dependent FtsH protease are required for sigma32 proteolysis in vivo.
      Bradyrhizobium japonicum expresses three sigma32-type transcription factors,
      RpoH1, RpoH2, and RpoH3, which are functional in E. coli. We compared the
      stability of these sigma factors with E. coli sigma32 stability. In E. coli C600
      (wild-type), the half-lives of sigma32, RpoH1, RpoH2 and RpoH3 were 30 s, 7 min,
      4 min and 4 min, respectively. The first three proteins were stabilized in ftsH
      mutant backgrounds, indicating that they are degraded by FtsH in the wild-type.
      Proteolysis of RpoH3 was FtsH-independent because this sigma factor was not
      stabilized in ftsH mutants. Interestingly, in a purified in vitro system, all
      four RpoH proteins were degraded by FtsH, indicating that in vivo protein
      degradation depends on additional cellular factors. Rationally designed point
      mutations of sigma32 and RpoH1 suggested that the highly conserved RpoH box does
      not play a major role in conferring stability to RpoH factors. Presumably,
      several regions distributed along the primary sequence of the sigma factor are
      important for FtsH-mediated proteolysis. Finally, we provide evidence that
      proteolysis of RpoH factors in vivo depends on the DnaK machinery, irrespective
      of the protease involved.

PMID- 10903519
TI  - Intracellular inhibition of blood group A glycosyltransferase.
AB  - We report the intracellular inhibition of blood group A N
      acetylgalactosaminyltransferase in the human colorectal carcinoma cell line HT29
      by 3-amino-3-deoxy-[Fucalpha(1-2)]Galbeta-O(CH2)7CH3. Inhibition was demonstrated
      with a novel capillary electrophoresis assay that monitored decreased
      intracellular conversion of fluorescently labelled Fucalpha(1-2)Gal-R acceptor to
      the corresponding A epitope, GalNAcalpha(1-3)[Fucalpha(1-2)]Galbeta-R. Growth of
      HT29 cells with either the amino-inhibitor or a competitive substrate, Fucalpha(1
      2)Galbeta-O(CH2)7CH3, also resulted in decreased expression of blood group A
      determinants on cell-associated glycoproteins, as detected by immunoprecipitation
      analysis using A-specific monoclonal antibodies. Furthermore, exposure of these
      cells to the amino-inhibitor or competitive substrate resulted in significant
      reduction of cell-surface expression of blood group A determinants. As integrin
      alpha3beta1, a cell-surface receptor mediating cell-cell and cell-extracellular
      matrix interactions, was shown previously to be a major carrier of blood group A
      determinants on HT29 cells, the studies described herein highlight the potential
      usefulness of these compounds for elucidating the role of blood group A
      determinants in biological phenomena.

PMID- 10903520
TI  - The structure-function relationship of functionally distinct but structurally
      similar hexose transporters from Trypanosoma congolense.
AB  - We have previously characterized, in Trypanosoma brucei, a multigene family
      encoding two developmentally regulated glucose transporters that are 80%
      identical at the amino-acid level. We report here the characterization of the
      homologous glucose transporters (TcoHT1 and TcoHT2) in Trypanosoma congolense, an
      African trypanosome responsible for disease in domestic animals. Both TcoHT
      isoforms, which are 92.4% identical, are encoded by a single cluster of genes
      containing two copies of TcoHT1 and three copies of TcoHT2 arranged alternately.
      Northern blot analysis revealed that TcoHT2 is expressed in all of the adaptive
      forms, while mRNA encoding TcoHT1 is only present in the metacyclic and
      bloodstream forms of T. congolense. When transfected with the TcoHT2 gene,
      Chinese Hamster Ovary cells express a hexose transporter with properties similar
      to those of the T. congolense procyclic forms (Km D-glucose = 41 microM versus 64
      microM). In contrast to TcoHT2, TcoHT1 expressed in the Chinese hamster ovary
      cells appeared to be a relatively low affinity glucose transporter (Ki D-glucose
      = 0.8 mM). To determine the region(s) involved in the different apparent
      affinities for glucose, a chimera analysis was undertaken on the TcoHT isoforms.
      This study shows that amino-acid residues important for D-glucose recognition are
      located in the central region (between transmembrane domains 3 and 7) and in the
      C-terminal intracellular domain of TcoHT2. Site directed mutagenesis identified
      Ser193 located within transmembrane helix 4 as a key residue in relaxing the
      apparent affinity of TcoHT1 for glucose.

PMID- 10903521
TI  - Simulation of electrostatic effects in Fab-antigen complex formation.
AB  - A model based on the Poisson-Boltzmann equation has been used to model
      electrostatics in Anti-p24 (HIV-1) Fab-antigen association. The ionization state
      at different pH values has been simulated and the results have been used to
      estimate the stability at different pH values and to generate electrostatic
      potential maps at physiological ionic strength. The analysis of the electrostatic
      potential at the solvent-accessible surface shows that residues involved in
      binding are mostly found in the highest, but also in lowest potential regions.
      Brownian dynamics simulations have been used to estimate the enhancement of the
      association rate due to electrostatics which appears limited (approximately 2 at
      150 mM ionic strength and approximately 3 at 15 mM ionic strength). A much more
      pronounced effect is observed upon increase of the charge of the diffusing
      particle. These results compare well with results obtained previously in similar
      studies on different systems and may serve to estimate the expected order of
      magnitude of electrostatic effects on association rates in antibody-antigen
      systems.

PMID- 10903522
TI  - Amino-acid replacements in an internal region of tropomyosin alter the properties
      of the entire molecule.
AB  - Two isoforms of lobster muscle tropomyosin, a fast muscle type, fTm, and a slow
      muscle type, sTm1, are identical except for 15 residues within the region of
      amino acids 39-80, which corresponds to exon 2 of the tropomyosin genes of many
      phyla. Although the difference in the sequence does not include the terminal
      regions, the two isoforms are extremely different in viscosity, which is a good
      measure of the head-to-tail interaction strength and should be dependent on the
      conformation of the terminal 7-9 residues. To determine the influence of amino
      acid replacements in the internal region on the overall conformation and the
      functional properties of the molecule, we compared the physical properties of the
      two isoforms and their interactions with other proteins, such as actin and myosin
      subfragment 1 (S1). Limited proteolysis by trypsin and chymotrypsin showed that
      sTm1 is more susceptible than fTm at the sites outside the region with the
      replaced residues. Compared with fTm, sTm1 showed higher viscosity, had a higher
      actin affinity, and inhibited acto-S1 ATPase to a greater extent. Finally, the
      binding isotherm of S1-ADP to actin-sTm1 is less sigmoidal than that to actin
      fTm. These results indicate that the amino-acid replacements in the internal
      region alter the conformation and the physical properties of the entire molecule
      as well as its interactions with actin and myosin.

PMID- 10903523
TI  - Expression of silicatein and collagen genes in the marine sponge Suberites
      domuncula is controlled by silicate and myotrophin.
AB  - The major skeletal elements in the (Porifera) sponges, are spicules formed from
      inorganic material. The spicules in the Demospongiae class are composed of
      hydrated, amorphous silica. Recently an enzyme, silicatein, which polymerizes
      alkoxide substrates to silica was described from the sponge Tethya aurantia. In
      the present study the cDNA encoding silicatein was isolated from the sponge
      Suberites domuncula. The deduced polypeptide comprises 331 amino acids and has a
      calculated size of Mr 36 306. This cDNA was used as a probe to study the
      potential role of silicate on the expression of the silicatein gene. For these
      studies, primmorphs, a special form of aggregates composed of proliferating
      cells, have been used. It was found that after increasing the concentration of
      soluble silicate in the seawater medium from around 1 microM to approximately 60
      microM, this gene is strongly upregulated. Without additional silicate only a
      very weak expression could be measured. Because silica as well as collagen are
      required for the formation of spicules, the expression of the gene encoding
      collagen was measured in parallel. It was also found that the level of
      transcripts for collagen strongly increases in the presence of 60 microM soluble
      silicate. In addition, it is demonstrated that the expression of collagen is also
      upregulated in those primmorphs which were treated with recombinant myotrophin
      obtained from the same sponge. Myotrophin, however, had no effect on the
      expression of silicatein. From these data we conclude that silicate influences
      the expression of the enzyme silicatein and also the expression of collagen, (via
      the mediator myotrophin).

PMID- 10903524
TI  - The riboflavin/FAD cycle in rat liver mitochondria.
AB  - Here we provide evidence that mitochondria isolated from rat liver can synthesize
      FAD from riboflavin that has been taken up and from endogenous ATP. Riboflavin
      uptake takes place via a carrier-mediated process, as shown by the inverse
      relationship between fold accumulation and riboflavin concentration, the
      saturation kinetics [riboflavin Km and Vmax values were 4.4+/-1.3 microM and 35+/
      5 pmol x min(-1) (mg protein)(-1), respectively] and the inhibition shown by the
      thiol reagent mersalyl, which cannot enter the mitochondria. FAD synthesis is due
      to the existence of FAD synthetase (EC 2.7.7.2), localized in the matrix, which
      has as a substrate pair mitochondrial ATP and FMN synthesized from taken up
      riboflavin via the putative mitochondrial riboflavin kinase. In the light of
      certain features, including the protein thermal stability and molecular mass,
      mitochondrial FAD synthetase differs from the cytosolic isoenzyme. Apparent Km
      and apparent Vmax values for FMN were 5.4+/-0.9 microM and 22.9+/-1.4 pmol x min(
      1) x (mg matrix protein)(-1), respectively. Newly synthesized FAD inside the
      mitochondria can be exported from the mitochondria in a manner sensitive to
      atractyloside but insensitive to mersalyl. The occurrence of the riboflavin/FAD
      cycle is proposed to account for riboflavin uptake in mitochondria biogenesis and
      riboflavin recovery in mitochondrial flavoprotein degradation; both are
      prerequisites for the synthesis of mitochondrial flavin cofactors.

PMID- 10903525
TI  - Hormonal contraception and chemoprevention of female cancers.
AB  - Oral contraceptive (OC) use significantly reduces the risk of endometrial and
      ovarian cancer, has only a minimal effect on breast cancer, but may increase the
      risk of cervical cancer. These effects can be readily explained in terms of the
      effects of OCs on cell proliferation in these tissues. This analysis suggests how
      a hormonal contraceptive based on a GnRH agonist plus low-dose add-back sex
      steroids could be made that would greatly reduce lifetime risk of breast and
      ovarian cancer. Such a hormonal contraceptive is also likely to significantly
      reduce the lifetime risk of cervical cancer. It is also likely to reduce the risk
      of endometrial cancer, although not to the same extent as OCs.

PMID- 10903526
TI  - Hormone therapy in epithelial ovarian cancer.
AB  - Although epidemiologic studies, animal experiments and receptor studies have
      shown that not only normal ovaries but also many malignant ovarian tumors can be
      considered as endocrine related and hormone dependent, the place of hormonal
      therapy in the management of patients with ovarian cancer remains unsettled. Most
      trials of hormonal treatment in ovarian cancer have been retrospective, involved
      only limited numbers of patients, and lacked important patient-related data and
      information pertaining to tumor characteristics. In addition, a variety of
      hormonal preparations with different degrees of potency and in different dosages
      were included in these studies. A literature review shows that response to
      hormonal therapy even in a preterminal setting, is modest, with about 8%
      objective response but almost no side effects. In a similar patient setting, more
      toxic therapeutic agents do not yield a better response. The place of hormonal
      therapy in the management of patients with epithelial ovarian cancer needs more
      thorough evaluation in well-designed randomized trials.

PMID- 10903528
TI  - PTEN, a unique tumor suppressor gene.
AB  - For many years, it has been thought that the chromosome region 10q22-24 includes
      one or more genes that appear to play a role in several human malignancies. PTEN
      is a new tumor suppressor gene encoding a dual-specificity phosphatase that was
      cloned simultaneously by three groups (Li & Sun 1997, Li et al. 1997, Steck et
      al. 1997), two of which used a positional cloning approach to identify genes in
      chromosome 10 (Li et al. 1997, Steck et al. 1997). While several protein kinases
      have been implicated as oncogenes, and phosphatases have long been known
      frequently to antagonize their function, there has been no direct demonstration
      of the role of phosphatases in tumor development (Myers & Tonks 1997). PTEN
      characterization as a bona fide tumor suppressor gene has confirmed that a
      deficient phosphatase activity can lead to cancer, as detailed by studies that
      are described below.

PMID- 10903529
TI  - Morphology, distribution, and variability of the epicardiac neural ganglionated
      subplexuses in the human heart.
AB  - Concomitant with the development of surgical treatment of cardiac arrythmias and
      management of myocardial ischemia, there is renewed interest in morphology of the
      intrinsic cardiac nervous system. In this study, we analyze the topography and
      structure of the human epicardiac neural plexus (ENP) as a system of seven
      ganglionated subplexuses. The morphology of the ENP was revealed by a
      histochemical method for acetylcholinesterase in whole hearts of 21 humans and
      examined by stereoscopic, contact, and bright-field microscopy. According to
      criteria established to distinguish ganglionated subplexuses, they are epicardiac
      extensions of mediastinal nerves entering the heart through discrete sites of the
      heart hilum and proceeding separately into regions of innervation by seven
      pathways, on the courses of which epicardiac ganglia, as wide ganglionated
      fields, are plentifully located. It was established that topography of epicardiac
      subplexuses was consistent from heart to heart. In general, the human right
      atrium was innervated by two subplexuses, the left atrium by three, the right
      ventricle by one, and the left ventricle by three subplexuses. The highest
      density of epicardiac ganglia was identified near the heart hilum, especially on
      the dorsal and dorsolateral surfaces of the left atrium, where up to 50% of all
      cardiac ganglia were located. The number of epicardiac ganglia identified for the
      human hearts in this study ranged from 706 up to 1,560 and was not correlated
      with age in most heart regions. The human heart contained on average 836 +/- 76
      epicardiac ganglia. The structural organization of ganglia and nerves within
      subplexuses was observed to vary considerably from heart to heart and in relation
      to age. The number of neurons identified for any epicardiac ganglion was
      significantly fewer in aged human compared with infants. By estimating the number
      of neurons within epicardiac ganglia and relating this to the number of ganglia
      in the human epicardium, it was calculated that approximately 43,000 intrinsic
      neurons might be present in the ENP in adult hearts and 94,000 neurons in young
      hearts (fetuses, neonates, and children). In conclusion, this study demonstrates
      the total ENP in humans using staining for acetylcholinesterase, and provides a
      morphological framework for an understanding of how intrinsic ganglia and nerves
      are structurally organized within the human heart.

PMID- 10903531
TI  - Blood group antigen expression in the rat colon I. age-dependent and region
      related changes.
AB  - The blood group antigens H, A, B, and Le(b) are oncofetal antigens of the human
      distal colon. Although these antigens are present in the digestive mucosa of the
      rat, little is known about their ontogenic expression in the developing rat
      colon. The present study was undertaken to assess age-dependent and region
      related changes of blood group antigens during colonic development and maturation
      with the aim of determining their fetal phenotype. Antigen expression was
      assessed by immunohistochemistry using H-, A-, B-, Le(a)-, and Le(b)-specific
      monoclonal antibodies and formalin-fixed, paraffin-embedded colon sections from
      fetal, suckling, weanling, and adult rats. Staining of antigen was analyzed with
      respect to its locations in colonic goblet cells, brush borders, and columnar
      cells. H, B, and Le(b) antigens were expressed by goblet cells of the distal
      colon, beginning at 20 days of gestation, but expression was lost from the colon
      during the first postnatal week, thus exhibiting a fetal phenotype. H and Le(b),
      but not B, were also expressed by goblet cells of the fetal proximal colon;
      however, unlike that of the distal colon, their expression increased
      progressively during postnatal development until adulthood. Fetal phenotypic
      expression was observed in the brush border of the proximal and distal colon for
      H antigen, whereas it was observed in that of the distal colon for B antigen. No
      fetal phenotypic expression of H, B, and Le(b) by columnar cells of the colon was
      observed. Antigen A was expressed by goblet cells, brush border, and columnar
      cells of the entire colon at all ages, in concert with the development and
      maturation of the colon. Therefore, its expression in the rat colon was not fetal
      in nature. Le(a) was not detected in the colon at any age, except for some
      sporadic staining in the Golgi zone of columnar cells of the postnatal proximal
      colon. In conclusion, these data indicate significant age- and region-related
      changes of blood group antigen expression in the rat colon. Because the fetal
      phenotypic expression of H, B, and Le(b) by goblet cells of the distal colon
      mimics that in the human distal colon, the adult rat colon is a potentially
      useful model for assessing the effects of cocarcinogenic dietary factors,
      including ethanol, that may induce reexpression of these so-called oncofetal
      tumor-associated antigens of the colon.

PMID- 10903530
TI  - Comparative analysis of HOXC-9 gene expression in murine hemochorial and caprine
      synepitheliochorial placentae by in situ hybridization.
AB  - Mammalian placentae exhibit wide structural diversity among different species and
      are formed under intricate interplay between the embryonic trophoblast and the
      maternal endometrial cells. Increasing evidence in the literature indicates a
      possible role played by homeobox genes in the complex placental organogenesis.
      Although the expression of all HOX 9 paralogs has been demonstrated both in
      highly invasive murine hemochorial placentae and in non-invasive caprine
      synepitheliochorial placentae, no reports so far published in the literature
      described the patterns of gene expression of Hoxc-9 in the murine nor those of
      HOXC-9 in the caprine placenta at cellular levels. We carried out comparative
      analyses of the location and identity of the cells expressing Hoxc-9/HOXC-9
      during various stages of placentation in the murine hemochorial and caprine
      synepitheliochorial placentae by means of in situ hybridization using murine Hoxc
      9 or caprine HOXC-9 cRNA probe, respectively. The results demonstrated that Hoxc
      9 mRNA was expressed at high levels in giant trophoblast cells of murine
      placentae on Days 12-19, but not on Day 8. Similar analysis of caprine Day 75 and
      Day 100 placentae revealed that the binucleate trophoblast cells that penetrate
      the uterine luminal epithelial cell layer, strongly expressed HOXC-9 mRNA.
      Although the functional significance of Hoxc-9/HOXC-9 gene expression in
      trophoblast cells remains to be elucidated, it was suggested that it might play a
      role in the regulation of invasiveness or endocrine activities in the murine
      giant trophoblast cells and/or the caprine binucleate trophoblast cells.

PMID- 10903527
TI  - Tissue architecture and breast cancer: the role of extracellular matrix and
      steroid hormones.
AB  - The changes in tissue architecture that accompany the development of breast
      cancer have been the focus of investigations aimed at developing new cancer
      therapeutics. As we learn more about the normal mammary gland, we have begun to
      understand the complex signaling pathways underlying the dramatic shifts in the
      structure and function of breast tissue. Integrin-, growth factor-, and steroid
      hormone-signaling pathways all play an important part in maintaining tissue
      architecture; disruption of the delicate balance of signaling results in dramatic
      changes in the way cells interact with each other and with the extracellular
      matrix, leading to breast cancer. The extracellular matrix itself plays a central
      role in coordinating these signaling processes. In this review, we consider the
      interrelationships between the extracellular matrix, integrins, growth factors,
      and steroid hormones in mammary gland development and function.

PMID- 10903532
TI  - Blood group antigen expression in the rat colon II. Modulation by dietary ethanol
      consumption.
AB  - In the accompanying article, we established that in the rat distal colon
      expression of H, B, and Le(b) blood group antigens by goblet cells is
      phenotypically fetal in nature. Because of the cocarcinogenic property of
      ethanol, the present study examined the effects of dietary ethanol consumption,
      fasting, and withdrawal on the expression of these antigens in the adult rat
      colon. To that effect, male adult Sprague-Dawley rats were pair-fed ethanol
      containing or control Lieber-DeCarli liquid diets for 3 weeks. The effects of
      ethanol withdrawal were studied in rats fed the ethanol-containing diet for 3
      weeks followed by the control diet for 1, 3, and 6 days. In rats fed the control
      diet, no antigen expression in the distal colon was observed, as expected.
      Ethanol feeding for 3 weeks resulted in a striking reappearance of H, B, and
      Le(b) antigens in goblet cells of the distal colon. In colonic crypts, a lower-to
      upper crypt gradient of increasing numbers of positive goblet cells was present,
      suggesting that the induction of antigen expression paralleled the
      differentiation of goblet cells. After an overnight fast, the number of positive
      cells was significantly decreased. Withdrawal of ethanol for 1 day further
      decreased the number of positive goblet cells. The decrease was reflected by a
      downward shift in the number of positive cells per crypt column, which was more
      striking in the lower and mid-crypt segments than in the upper segment,
      suggesting that antigen expression was more labile in immature differentiating
      goblet cells than in mature ones. No antigen staining of goblet cells was
      detected after 3 and 6 days of ethanol withdrawal. Hence, expression of H, B, and
      Le(b) antigens by goblet cells of the distal colon can be modulated by ethanol
      consumption. Expression in the distal colon of A and Le(a) antigens, which did
      not exhibit a fetal phenotype, was not affected by ethanol feeding. In
      conclusion, because of the oncofetal phenotype of H, B, and Le(b) antigens, their
      reappearance in the distal colon may serve as a cytochemical marker for early
      recognition of epithelial changes of the colon in ethanol-related
      cocarcinogenesis before more overt manifestations of neoplasia.

PMID- 10903533
TI  - Ultrastructural cytochemical characterization of collagen-associated
      proteoglycans in the endometrium of mice.
AB  - The decidual reaction in mice is characterized by the transformation of a
      specific population of endometrial fibroblasts into epithelioid cells, known as
      decidual cells. An important feature of decidualization in mice is a remarkable
      modification of the endometrial extracellular matrix. The present work is an
      ultrastructural cytochemical study of matrix with the purpose of analyzing the
      arrangement of collagen-associated proteoglycans (PGs) at various regions of
      nulliparous endometrium and of the antimesometrial decidua of mice using the
      cationic dye cuprolinic blue associated with enzymatic treatments with
      chondroitinase ABC, chondroitinase AC, and hyaluronidase. The staining with
      cuprolinic blue showed PGs as rods and granules of several sizes. Rods measuring
      40-60 nm in length (named F2-rods) were apposed to thin collagen fibrils whereas
      granules were associated with thick collagen fibrils, particularly in the region
      occupied by mature decidual cells on the 7th day of pregnancy. The amount of
      granules was higher than that of F2-rods. Both F2-rods and granules were affected
      by chondroitinase ABC or AC treatment, indicating that they were PGs containing
      chondroitin sulfate and dermatan sulfate chains. However, the granules associated
      with thick collagen fibrils were more resistant to chondroitinase AC treatment
      than F2-rods, indicating the presence of dermatan sulfate chains that contain
      both L-iduronic and D-glucuronic acid sugar residues. We suggest that the
      differences of the nature and amount of PGs may be associated with the changes of
      the thickness of collagen fibrils observed during decidualization of the
      endometrium in the mouse.

PMID- 10903534
TI  - Pathology of intrinsic cardiac neurons from ischemic human hearts.
AB  - Various populations of intrinsic cardiac neurons influence regional cardiac
      function tonically. It is not known whether such neurons are affected by disease
      states and, if so, in what manner. Therefore, the morphology of intrinsic cardiac
      ganglia obtained from patients with angiographic evidence of compromised regional
      coronary blood supply was studied. Posterior atrial ganglia and surrounding fat,
      removed at the time of cardiac surgery, were placed immediately in saline and
      within 15-120 min (average of about 40 min) in 0.5% paraformaldehyde/2.5%
      glutaraldehyde. In 32 studied ganglia, 35% of 473 intrinsic cardiac neurons
      displayed striking pathological changes at the light and ultrastructural level.
      The other cells displayed normal morphology. The cytoplasm of 74% of the abnormal
      cells had one or more of three types of inclusions: (1) darkly stained lamellated
      inclusions (Type I), (2) membrane-bound whorls and parallel arrays of lightly
      stained membranes, as well as fine granular material (Type II), or (3) concentric
      layers of lightly stained membranes with a darker, granular core (Type III).
      Neurons with inclusions were markedly enlarged (66 x 54 microm vs. 40 x 34 microm
      for normal neurons) and displayed fewer dendrites. Some neurons contained
      electron lucent vacuoles indicative of degeneration while others showed frank
      degeneration, being fragmented, shrunken, and misshapen. Phagocytic cells
      containing lamellated inclusions and cellular debris were found in ganglia with
      abnormal neurons. Some axon terminals also displayed degenerative changes. The
      identification of pathological changes in the human intrinsic cardiac nervous
      system has implications with respect to the functional integrity of this final
      common regulator of cardiac function in disease states.

PMID- 10903535
TI  - Synthesis and receptor sites of endothelin-1 in the rat liver vasculature.
AB  - Immunocytochemical localization of big endothelin-1 (big ET-1), ET-1, and ET
      receptor A and B (ET(A) and ET(B)), and gene expression of prepro ET-1 mRNA were
      examined on the rat liver vasculature. Immunoreactivities for big ET-1 and ET-1
      were preferentially seen along the endothelium of interlobular veins (IV) and
      artery (IA), although the staining intensity was more pronounced in IV.
      Expression of preproET-1 mRNA was detected in both vascular endothelia and the
      signal intensity was more prevalent in IV. Immunoelectron microscopy showed that
      rough endoplasmic cisterns were immunoreactive for big ET-1, while Weibel-Palade
      (WP) bodies, a storage site for ET-1, were immunoreactive for ET-1 in endothelial
      cells of IV. These results indicate that endothelial cells of IV are the major
      site of synthesis of ET-1, which is extracellularly secreted by degranulation
      and/or exocytosis of WP bodies. Hepatic stellate cells (HSCs), especially of the
      plasma membrane of perisinusoidal and interhepatocellular processes, were
      immunoreactive for both ET(A) and ET(B) receptor antibodies. These findings
      suggest that ET-1 receptor-mediated HSC contraction is involved in the regulation
      of hepatic sinusoidal blood flow as previously cited in mammalian liver
      cirrhosis. We also showed that sarcolemma and caveoles in the smooth muscle cells
      of the media of IV, and its branches before reaching the hepatic sinusoids, were
      immunoreactive for ET(A) receptor antibody. The results suggest that such
      vessels, which contains a large amount of hepatic blood inflow, participate in
      pump mechanism toward hepatic sinusoidal circulation in a receptor-mediated
      paracrine fashion.

PMID- 10903536
TI  - Neurotrophin receptor (p75) in the trigeminal thalamus of the rat: development,
      response to injury, transient vibrissa-related patterning, and retrograde
      transport.
AB  - We report on the transient, patterned expression of p75 in the ventrobasal (VB)
      thalamus, the major thalamic relay for somatosensation. We immunostained the
      brains of developing rats ranging in age from embryonic day (E) 14.5 to postnatal
      day (PD) 15 with an antibody against p75. To compare p75 expression with the
      developing synaptic organization within VB, we also immunolocalized the synaptic
      vesicle-associated protein, synaptophysin (SYN), on alternate sections. p75
      immunoreactivity (IR) was dense and uniform in the ventroposterior medial nucleus
      (VPM) in the late embryonic and early postnatal periods (E 16.5 to PD 3). In
      contrast, from PD 4-10, p75-IR in the VPM was patterned, reminiscent of
      cytochrome-oxidase-stained barreloids, a characteristic feature of the VB in
      rodents. By PD 14, p75-IR in the VPM was no longer detectable. The
      ventroposterior lateral nucleus (VPL), in contrast, exhibited no p75-IR. No p75
      IR was detected in the ventroposterior lateral nucleus (VPL) at any developmental
      stage in which VPM could be distinguished from VPL. Light, but clearly patterned
      SYN-IR, first detectable on PD 2-3, increased in intensity in both VPL and VPM
      through PD 15. Sectioning the infraorbital nerve on PD 0 resulted in blurred
      patterns of p75- and SYN-IR within VPM in PD 7-9 rat pups. Removing large
      portions of the somatosensory cortex on PD 0 resulted in subsequent greatly
      reduced p75- and SYN-IR within VB. To specify the source of the p75-IR terminals,
      we stereotaxically injected into the VPM of PD 4-5 rats a monoclonal antibody to
      p75. One to 2 days later, IR of retrogradely transported p75 antibodies could be
      traced within axons and cell bodies of neurons associated with the
      trigeminothalamic pathway through the caudal diencephalon and mesencephalon;
      labelling was confined to the contralateral trigeminal principal sensory nucleus.
      The observed, transiently patterned p75-IR in VPM the early postpartum period
      suggests a role for p75 in synaptogenesis and pattern formation.

PMID- 10903537
TI  - Burden of disease and priority setting.

PMID- 10903538
TI  - Using health production functions to evaluate treatment effectiveness: an
      application to a community mental health service.
AB  - The randomized controlled trial (RCT) is the recommended means of evaluating
      health care effectiveness and cost-effectiveness. Whilst representing a 'gold
      standard' in health services research, RCT evidence on the clinical and economic
      desirability of services and treatments is often absent. Where RCT evidence is
      lacking, or where it is infeasible to implement randomized controlled
      comparisons, longitudinal observational and naturalistic data sources when
      analysed appropriately can yield useful insights regarding the clinical
      effectiveness and economic efficiency of treatments. In this paper we demonstrate
      the utility of applying panel estimation methods to data from an Italian
      psychiatric case register as a means of modelling the mental health outcomes of
      patients referred to a community-based mental health service. Emphasis is placed
      on quantifying the clinical effectiveness of consultations with different mental
      health professionals (including in-patient days) and whether service outcomes are
      affected by psychiatric diagnosis. The impact of service consultations and their
      interaction with different types of psychiatric diagnosis on a measure of patient
      mental health are found to be statistically significant, although the size of
      these effects are not substantial from a clinical perspective.

PMID- 10903539
TI  - Preference measurement using conjoint methods: an empirical investigation of
      reliability.
AB  - The application of conjoint measurement to the field of health economics is
      relatively new, although there is growing interest and there have been a number
      of studies undertaken recently. Wider acceptance of the technique requires
      methodological issues concerning both reliability and validity to be addressed.
      This paper reports an empirical investigation of the test-retest reliability of
      the discrete choice conjoint measurement approach in health care. This
      investigation of conjoint reliability was framed using the clinical context of
      investigation and treatment of knee injuries. A high level of reliability at both
      the input data and results levels was demonstrated.

PMID- 10903540
TI  - Cost function estimation: the choice of a model to apply to dementia.
AB  - Statistical analysis of cost data is often difficult because of highly skewed
      data resulting from a few patients who incur high costs relative to the majority
      of patients. When the objective is to predict the cost for an individual patient,
      the literature suggests that one should choose a regression model based on the
      quality of its predictions. In exploring the econometric issues, the objective of
      this study was to estimate a cost function in order to estimate the annual health
      care cost of dementia. Using different models, health care costs were regressed
      on the degree of dementia, sex, age, marital status and presence of any co
      morbidity other than dementia. Models with a log-transformed dependent variable,
      where predicted health care costs were re-transformed to the unlogged original
      scale by multiplying the exponential of the expected response on the log-scale
      with the average of the exponentiated residuals, were part of the considered
      models. The root mean square error (RMSE), the mean absolute error (MAE) and the
      Theil U-statistic criteria were used to assess which model best predicted the
      health care cost. Large values on each criterion indicate that the model performs
      poorly. Based on these criteria, a two-part model was chosen. In this model, the
      probability of incurring any costs was estimated using a logistic regression,
      while the level of the costs was estimated in the second part of the model. The
      choice of model had a substantial impact on the predicted health care costs, e.g.
      for a mildly demented patient, the estimated annual health care costs varied from
      DKK 71 273 to DKK 90 940 (US$ 1 = DKK 7) depending on which model was chosen. For
      the two-part model, the estimated health care costs ranged from DKK 44714, for a
      very mildly demented patient, to DKK 197 840, for a severely demented patient.

PMID- 10903541
TI  - The cost-effectiveness of evidence-based guidelines and practice for screening
      and prevention of tuberculosis.
AB  - INTRODUCTION: The potential cost-effectiveness of screening depends on the risk
      of tuberculosis (TB) in the population being screened and the rate at which the
      screening outcome (prevention) is achieved. AIMS: To compare the cost
      effectiveness of contact screening for TB for: (1) contact screening as it
      actually occurred in Victoria in 1991 (Model 1); (2) the process which should
      have occurred had the 1991 contact screening guidelines been followed (Model 2);
      (3) a hypothetical evidence-based model (Model 3). METHODS: Three models were
      constructed according to the aims. The cost-effectiveness of contact screening is
      presented as costs to government per unit outcome (in the form of cases
      prevented, cases found and contacts traced) for each model. Assumptions about
      disease behaviour were consistent between models. A sensitivity analysis was
      performed to examine the effect of the assumptions made in Model 3 about rates of
      referral and treatment of infected contacts, and about the efficacy of isoniazid
      (INH) in preventing TB. RESULTS: The total cost of Model 1 was greater than that
      of the other Models. Model 1 is the least cost-effective, costing $309 065 per
      case prevented, and Model 3 is the most cost-effective, costing $32 210 per case
      prevented. The cost of Model 2 was $58 742 per case prevented. The incremental
      cost-effectiveness of Model 3 compared to Model 2 is $107 per additional contact
      screened, and $3881 per additional case prevented. Case finding is not as cost
      effective as best-practice case prevention, ranging from $231 799 per case found
      in Model 1 to $205 596 per case found in Model 2. The sensitivity analysis shows
      that the cost-effectiveness of Model 3 decreases with lower referral rates, lower
      rates of preventive therapy, and lower efficacy of INH. However, even allowing
      for reduced programme parameters, Model 3 is most cost-effective. DISCUSSION:
      Costing policy options is an important component of programme delivery, but needs
      to be considered in the context of the product being purchased, e.g. the
      prevention of disease, or case finding. Case finding as a product of contact
      screening is expensive in all three models. Prevention of TB, on the other hand,
      can be cost-effective, as shown in Model 3. It was least cost-effective in Model
      1, largely because prevention was not considered a priority, and few infected
      contacts actually received preventive therapy. Clear programme aims, adherence to
      guidelines and high rates of preventive therapy are essential in order to achieve
      cost-effectiveness.

PMID- 10903542
TI  - Determinants of ambulatory treatment mode for mental illness.
AB  - We estimate a reduced-form bivariate probit model to analyse jointly the choice
      of ambulatory treatment from the specialty mental health sector and/or the use of
      psychotropic drugs for a nationally representative sample of US household
      residents. We find significant differences in treatment choice by education,
      gender, race and ethnicity, while controlling for several aspects of self
      reported mental health and treatment attitudes. For example, while women are more
      likely than men to use the specialty mental health sector and more likely to take
      psychotropic medications, this difference between men and women is much greater
      for psychotropic medications. The estimated differences may reflect patient
      preferences in a manner traditionally assumed when interpreting these
      coefficients in such equations, but we discuss how they may also reflect biases
      and misperceptions on the parts of patients and providers. We also discuss how
      our results relate to some findings and policies in the general health care
      sector.

PMID- 10903543
TI  - A multilevel modelling approach to analysis of patient costs under managed care.
AB  - The growth of the managed care model of health care delivery in the USA has led
      to broadened interest in the performance of health care providers. This paper
      uses multilevel modelling to analyse the effects of managed care penetration on
      patient level costs for a sample of 24 medical centres operated by the Veterans
      Health Administration (VHA). The appropriateness of a two level approach to this
      problem over ordinary least squares (OLS) is demonstrated. Results indicate a
      modicum of difference in institutions' performance after controlling for patient
      effects. Facilities more heavily penetrated by the managed care model may be more
      effective at controlling costs of their sicker patients.

PMID- 10903544
TI  - Competition and dental services.
AB  - Dental services for adults are different from all other Norwegian health services
      in that they are provided by private producers (dentists) who have full freedom
      to establish a practice. They have had this freedom since the end of World War
      II. A further liberalization of the market for dental services occurred in
      November 1995, when the so-called normal tariff was repealed. The system changed
      from a fixed fee system to a deregulated fee system. In principle, the market for
      dental services for adults operates as a free competitive market, in which
      dentists must compete for a market share. The aim of this study was to study the
      short-term effects of competition. A comprehensive set of data on fees, practice
      characteristics, treatment profiles and factors that dentists take into account
      when determining fees was analysed. The main finding was that competition has a
      weak effect. No support was found for the theory that the level of fees is the
      result of monopolistic competition or monopoly. The results also provided some
      evidence against the inducement hypothesis. At this stage, it is interesting to
      notice that dentists do not seem to exploit the power they have to control the
      market. One explanation, which is consistent with the more recent literature, is
      that physicians' behaviour to a large extent is influenced by professional norms
      and caring concerns about their patients. Financial incentives are important, but
      these incentives are constrained by norms other than self-interest. The
      interpretation of the results should also take into account that the deregulation
      has operated for a short time and that dentists and patients may not yet have
      adjusted to changes in the characteristics of the market.

PMID- 10903545
TI  - Idiopathic environmental intolerances: overview.
AB  - The editor discusses usage of the terms "iidiopathic environmental intolerance,"
      "multiple chemical sensitivity," and "environmental illness." Also addressed are
      prevalence, theories of etiology, evaluation and treatment, and social and
      political implications.

PMID- 10903546
TI  - Idiopathic environmental intolerance: case definition issues.
AB  - Case definitions of the same phenomenon may be different for different purposes.
      Case definitions usually become more specific over time as more information about
      the condition becomes available. Idiopathic environmental intolerance is one of
      many labels for a heterogeneous group of conditions in which subjects describe
      multiple symptoms that are attributed to exposure to extremely low doses of
      common chemicals. Dr. Kreutzer presents issues in case definition for clinical
      purposes and for population-based studies, and makes recommendations for the
      clinician and for the public health investigator.

PMID- 10903547
TI  - Behavioral conditioning and idiopathic environmental intolerance.
AB  - Idiopathic environmental intolerance (IEI) is a poorly understood condition that
      may involve disturbances in immunologic, neurologic, endocrine, behavioral,
      emotional, and cognitive processes. This chapter reviews theories and evidence
      that behavioral conditioning processes, including pharmacologic sensitization,
      conditioned immunomodulation, and conditioned odor and taste aversions, may play
      a role in the development and maintenance of IEI. It also reviews the
      psychophysiologic concepts of individual response specificity and situational
      response stereotypy as potential explanations for the individual differences
      observed in specific responses to environmental stimuli in patients with IEI.
      Finally, the treatment implications of a conditioning account of IEI are
      discussed as part of a more comprehensive treatment approach that incorporates
      other behavioral and nonbehavioral strategies.

PMID- 10903548
TI  - Idiopathic environmental intolerances: results of challenge studies.
AB  - It has been postulated that psychophysiologic mechanisms may account for symptom
      generation in IEI. In this review, the similarity of IEI and panic disorder
      symptoms are noted. The results of various challenge studies, both with known
      panicogenic substances and self-identified triggers, are examined. Available data
      are consistent with the premise that IEI symptoms have a psychophysiologic basis.

PMID- 10903549
TI  - Chemosensory function and response in idiopathic environmental intolerance.
AB  - This chapter reviews the current literature on the possible role of olfactory and
      trigeminal chemosensory function in idiopathic environmental intolerances (IEI).
      Two general points emerge from the review. First, studies of chemosensory
      function in IEI patients indicate that, despite their self-reported "heightened
      sensitivity" and enhanced responsivity to environmental odors, when compared to
      healthy controls they generally are found to be equally or even less sensitive to
      odors as measured by objective psychophysical and electrophysiological measures
      of olfactory function. These studies point towards alterations in the cognitive
      processing of olfactory information as the major characteristic of IEI. Second,
      studies of the role of sensitivity and bias in olfactory and trigeminal
      chemosensory functioning indicate that nonsensory factors (e.g., attention, bias,
      personality) can dramatically alter the self-reported impact of exposure to
      volatile chemicals. Together, these general points suggest a perspective on IEI
      that views many symptoms of the disorder to primarily reflect the influence of
      nonsensory, cognitive processes on responses to environmental odors.

PMID- 10903550
TI  - The relationship of mental disorders and idiopathic environmental intolerance.
AB  - Idiopathic environmental intolerance (IEI) is an acquired condition with multiple
      symptoms associated with diverse environmental factors tolerated by most persons,
      not explained by known medical or psychiatric disorders. Data from clinical and
      epidemiologic samples show a robust association between IEI and lifetime
      psychiatric disorder, particularly mood, anxiety, somatoform, and personality
      disorders. IEI has not been associated with lifetime substance use disorders or
      psychotic disorders. The relationship of IEI and psychiatric disorder is
      important to acknowledge because it alerts clinicians to the fact that many
      persons diagnosed with IEI suffer treatable emotional illnesses, and because it
      suggests that some persons with mental illness are being misdiagnosed when their
      symptoms are misinterpreted as evidence of IEI.

PMID- 10903551
TI  - Sick building syndrome.
AB  - Dr. Hodgson summarizes what is known about human symptoms and discomfort in the
      built environment, and formulates several critical hypotheses that show striking
      parallels to the questions arising from discussions of the IEI/MCS syndrome.

PMID- 10903552
TI  - Chemical sensitivity and gulf war veterans' illnesses.
AB  - Dr. Proctor summarizes the current research literature describing Gulf War (GW)
      veterans' health issues, particularly as they pertain to chemical sensitivity
      (CS) and multiple chemical sensitivity (MCS) syndrome. In several studies of GW
      veterans, using differing criteria and varying assessment measures for CS and
      MCS, the prevalence rates for CS are reported to be 36-86% in Department of
      Veterans' Affairs patient populations and 0.8-20% in general cohorts of GW
      veterans. The rates of MCS are 2-6%. Targeted research is needed to adequately
      evaluate GW veterans' health concerns and MCS.

PMID- 10903553
TI  - Diagnostic evaluation and treatment of the patient presenting with idiopathic
      environmental intolerance.
AB  - This chapter addresses the diagnostic evaluation and treatment of the patient
      presenting with idiopathic environmental intolerance (IEI). Clinicians with
      different views about the pathogenesis of IEI may agree on clinical management
      programs aimed at improved symptom control and functional ability.

PMID- 10903554
TI  - Functional brain imaging in the assessment of multiple chemical sensitivities.
AB  - The author provides a brief overview of single photon emission computed
      tomography in the assessment of multiple chemical sensitivities.

PMID- 10903555
TI  - Use of neuropsychological testing in idiopathic environmental testing.
AB  - Individuals with idiopathic environmental intolerance (IEI) report fatigue,
      headaches, weakness, malaise, decreased attention/concentration, memory loss,
      disorientation, confusion, and psychological disturbances. These neurobehavioral
      symptoms may be a sign of possible alterations in the central nervous system
      (CNS). The evaluation of neurobehavioral functioning using standardized testing
      provides a surrogate measure of integrity of the CNS. However, the interpretation
      of neuropsychological test results must be made cautiously since this technique
      is extremely sensitive, but not specific. Abnormal test results could be due to a
      neurological disorder, a medical disorder, or a neuropsychiatric disorder.
      Therefore, when evaluating patients who present with symptoms of IEI, abnormal
      neurobehavioral results should not be attributed routinely to environmental
      chemical exposure until other causes are systematically ruled out.

PMID- 10903556
TI  - Psychological treatment of psychogenic idiopathic environmental intolerance.
AB  - This chapter focuses on the psychotherapy of individuals who suffer distress from
      functional somatic syndromes; specifically, idiopathic environmental intolerance
      (IEI). While patients believe environmental intolerances cause their distress,
      its origin is treated as psychological, mediated through psychophysiological
      systems and mechanisms associated with the stress response. Factors considered
      include stress and trauma premorbid to the alleged onset of IEI; somatization and
      its expression through affective, anxiety, and somatoform disorders; personality
      disorders and associated psychological defenses; motivation for the sick role;
      and iatrogenic suggestion and reinforcement of unsubstantiated toxicogenic
      theories and treatments. Psychotherapies include behavioral desensitization,
      cognitive-behavioral therapy, cognitive therapy, and psychotropic medications.
      The greatest challenge in treatment is to overcome the patient's disabling belief
      in a toxicogenic explanation for his or her symptoms.

PMID- 10903557
TI  - Immunologic parameters of multiple chemical sensitivity.
AB  - Immunologic abnormalities have long been advanced as a potential mechanism for
      multiple chemical sensitivity (MCS). An immunologic mechanism is supported in
      part by the systemic nature of the symptoms reported, the complex interactions
      known to exist between the immune system and other systems, and limited
      experimental evidence. However, there are both theoretical grounds for doubting
      an immunologic mechanism in MCS and methodological constraints in many of the
      studies that have been conducted in humans. The authors discuss the structure and
      function of the immune system as it potentially applies to MCS, the uses and
      limitations of immunologic testing, and the evidence for immunologic theories of
      MCS. They describe recent work to validate some of the immunologic tests used in
      MCS and consider opportunities for further research.

PMID- 10903558
TI  - In search of consciousness.

PMID- 10903559
TI  - Eyes of the world be free; you have nothing to lose but your chains.

PMID- 10903560
TI  - Neuroligation: building synapses around the neurexin-neuroligin link.

PMID- 10903561
TI  - Inhibition in inferotemporal cortex: generating selectivity for object features.

PMID- 10903562
TI  - Optimizing coverage in the cortex.

PMID- 10903563
TI  - Mapping drosophila olfactory axons

PMID- 10903564
TI  - A golgi stain for dendritic function?

PMID- 10903565
TI  - A time-less function for mouse timeless.
AB  - The timeless (tim) gene is essential for circadian clock function in Drosophila
      melanogaster. A putative mouse homolog, mTimeless (mTim), has been difficult to
      place in the circadian clock of mammals. Here we show that mTim is essential for
      embryonic development, but does not have substantiated circadian function.

PMID- 10903566
TI  - Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but
      not obese rats.
AB  - Insulin and leptin receptors are present in hypothalamic regions that control
      energy homeostasis, and these hormones reduce food intake and body weight in
      lean, but not obese, Zucker rats. Here we demonstrate that insulin, like leptin,
      hyperpolarizes lean rat hypothalamic glucose-responsive (GR) neurons by opening
      KATP channels. These findings suggest hypothalamic K ATP channel function is
      crucial to physiological regulation of food intake and body weight.

PMID- 10903567
TI  - Domain specificity in face perception.

PMID- 10903568
TI  - FFA: a flexible fusiform area for subordinate-level visual processing automatized
      by expertise.

PMID- 10903570
TI  - Convergent projections of Drosophila olfactory neurons to specific glomeruli in
      the antennal lobe.
AB  - Candidate Drosophila olfactory receptors (ORs) provide molecular tools to
      investigate how the organization of the Drosophila olfactory system determines
      the coding of olfactory stimuli. Neurons in the third antennal segment and
      maxillary palp appear to express different ORs. Individual olfactory neurons send
      axonal projections to glomeruli in the antennal lobe. Using transgenic flies, we
      provide evidence that the neurons expressing a given OR gene, which have cell
      bodies distributed among neurons expressing other ORs, converge in their
      projections to topographically fixed glomeruli in the antennal lobe. This
      convergence allows for the formation of an odotopic map in the antennal lobe
      whose organization could provide a basis for olfactory discrimination in
      Drosophila.

PMID- 10903569
TI  - SLO-2, a K+ channel with an unusual Cl- dependence.
AB  - The gating of different potassium channels depends on many diverse factors. We
      now report a unique example of a K+ channel with a Cl - dependence. The slo-2
      gene was cloned from Caenorhabditis elegans and is widely expressed in both
      neurons and muscles; it was highly abundant, as suggested by its high
      representation in the C. elegans EST database. SLO-2, like its paralogue, SLO-1,
      was also dependent on Ca 2+. We show by site-directed mutagenesis that its
      requirements for both Cl- and Ca2+ are synergistic and associated with the same
      functional domain. SLO-2's dependence on Cl - implies that intracellular Cl-
      homeostasis may be important in regulating cellular excitability through this
      unusual K+ channel.

PMID- 10903571
TI  - Calretinin modifies presynaptic calcium signaling in frog saccular hair cells.
AB  - To determine whether the concentrations of calcium-binding proteins present in
      some neurons and sensory cells are sufficient to influence presynaptic calcium
      signaling, we studied the predominant calcium-binding protein in a class of
      sensory hair cells in the frog ear. Based on antibody affinity and molecular
      weight, we identified this protein as calretinin. We measured its cytoplasmic
      concentration to be approximately 1.2 mM, sufficient to bind approximately 6 mM
      Ca2+. Calcium signaling was altered when the diffusible cytoplasmic components
      were replaced by an intracellular solution lacking any fast calcium buffer, and
      was restored by the addition of 1.2 mM exogenous calretinin to the intracellular
      solution. We conclude that calretinin, when present at millimolar concentration,
      can serve as a diffusionally mobile calcium buffer/transporter capable of
      regulating calcium signaling over nanometer distances at presynaptic sites.

PMID- 10903572
TI  - H2 histamine receptor-phosphorylation of Kv3.2 modulates interneuron fast
      spiking.
AB  - Histamine-containing neurons of the tuberomammilary nucleus project to the
      hippocampal formation to innervate H1 and H2 receptors on both principal and
      inhibitory interneurons. Here we show that H2 receptor activation negatively
      modulates outward currents through Kv3.2-containing potassium channels by a
      mechanism involving PKA phosphorylation in inhibitory interneurons. PKA
      phosphorylation of Kv3.2 lowered the maximum firing frequency of inhibitory
      neurons, which in turn negatively modulated high-frequency population
      oscillations recorded in principal cell layers. All these effects were absent in
      a Kv3.2 knockout mouse. These data reveal a novel pathway for histamine-dependent
      regulation of high-frequency oscillations within the hippocampal formation.

PMID- 10903573
TI  - Maternal care, hippocampal synaptogenesis and cognitive development in rats.
AB  - We report that variations in maternal care in the rat promote hippocampal
      synaptogenesis and spatial learning and memory through systems known to mediate
      experience-dependent neural development. Thus, the offspring of mothers that show
      high levels of pup licking and grooming and arched-back nursing showed increased
      expression of NMDA receptor subunit and brain-derived neurotrophic factor (BDNF)
      mRNA, increased cholinergic innervation of the hippocampus and enhanced spatial
      learning and memory. A cross-fostering study provided evidence for a direct
      relationship between maternal behavior and hippocampal development, although not
      all neonates were equally sensitive to variations in maternal care.

PMID- 10903574
TI  - Neuronal mechanisms of selectivity for object features revealed by blocking
      inhibition in inferotemporal cortex.
AB  - The inferotemporal cortex (area TE) of monkeys, a higher station of the visual
      information stream for object recognition, contains neurons selective for
      particular object features. Little is known about how and where this selectivity
      is generated. We show that blockade of inhibition mediated by gamma-aminobutyric
      acid (GABA) markedly altered the selectivity of TE neurons by augmenting their
      responses to some stimuli but not to others. The effects were observed for
      particular groups of stimuli related to the originally effective stimuli or those
      that did not originally excite the neurons but activated nearby neurons.
      Intrinsic neuronal interactions within area TE thus determine the final
      characteristic of their selectivity, and GABAergic inhibition contributes to this
      process.

PMID- 10903575
TI  - Form representation in monkey inferotemporal cortex is virtually unaltered by
      free viewing.
AB  - How are objects represented in the brain during natural behavior? Visual object
      recognition in primates is thought to depend on the inferotemporal cortex (IT).
      In most neurophysiological studies of IT, monkeys hold their direction of gaze
      fixed while isolated visual stimuli are presented (controlled viewing). However,
      during natural behavior, primates visually explore cluttered environments by
      changing gaze direction several times each second (free viewing). We examined the
      effect of free viewing on IT neuronal responses in monkeys engaged in a form
      recognition task. By making small, real-time stimulus adjustments, we produced
      nearly identically retinal stimulation during controlled and free viewing. Nearly
      90% of neuronal responses were unaffected by free viewing, and average stimulus
      selectivity was unchanged. Thus, neuronal representations that likely underlie
      form recognition are virtually unaltered by free viewing.

PMID- 10903576
TI  - Visual cortex maps are optimized for uniform coverage.
AB  - Cat visual cortex contains a topographic map of visual space, plus superimposed,
      spatially periodic maps of ocular dominance, spatial frequency and orientation.
      It is hypothesized that the layout of these maps is determined by two
      constraints: continuity or smooth mapping of stimulus properties across the
      cortical surface, and coverage uniformity or uniform representation of
      combinations of map features over visual space. Here we use a quantitative
      measure of coverage uniformity (c') to test the hypothesis that cortical maps are
      optimized for coverage. When we perturbed the spatial relationships between
      ocular dominance, spatial frequency and orientation maps obtained in single
      regions of cortex, we found that cortical maps are at a local minimum for c'.
      This suggests that coverage optimization is an important organizing principle
      governing cortical map development.

PMID- 10903577
TI  - The influence of urgency on decision time.
AB  - A fruitful quantitative approach to understanding how the brain makes decisions
      has been to look at the time needed to make a decision, and how it is affected by
      factors such as the supply of information, or an individual's expectations. This
      approach has led to a model of decision-making, consistent with recent
      neurophysiological data, that explains the observed variability of reaction times
      and correctly predicts the effects of altered expectations. Can it also predict
      what happens when the urgency of making the response changes? We asked subjects
      to make eye movements to low-visibility targets either as fast or as accurately
      as possible, and found that the model does indeed predict the timing of their
      responses: the degree of urgency seems to influence the criterion level at which
      a decision signal triggers a response.

PMID- 10903579
TI  - The dynamics of object-selective activation correlate with recognition
      performance in humans.
AB  - To investigate the relationship between perceptual awareness and brain activity,
      we measured both recognition performance and fMRI signal from object-related
      areas in human cortex while images were presented briefly using a masking
      protocol. Our results suggest that recognition performance is correlated with
      selective activation in object areas. Selective activation was correlated to
      object naming when exposure duration was varied from 20 to 500 milliseconds.
      Subjects' recognition during identical visual stimulation could be enhanced by
      training, which also increased the fMRI signal. Overall, the correlation between
      recognition performance and fMRI signal was highest in occipitotemporal object
      areas (the lateral occipital complex).

PMID- 10903578
TI  - Experience-dependent changes in cerebral activation during human REM sleep.
AB  - The function of rapid-eye-movement (REM) sleep is still unknown. One prevailing
      hypothesis suggests that REM sleep is important in processing memory traces.
      Here, using positron emission tomography (PET) and regional cerebral blood flow
      measurements, we show that waking experience influences regional brain activity
      during subsequent sleep. Several brain areas activated during the execution of a
      serial reaction time task during wakefulness were significantly more active
      during REM sleep in subjects previously trained on the task than in non-trained
      subjects. These results support the hypothesis that memory traces are processed
      during REM sleep in humans.

PMID- 10903580
TI  - Manual therapy and science: a marriage of convenience?

PMID- 10903581
TI  - Functional stability of the glenohumeral joint.
AB  - Normal shoulder function is determined by the stability provided by the passive,
      active and control subsystems of the joint complex. Given the complexity of the
      shoulder, it is not surprising that it is one of the most common joints
      presenting with pathology. Knowledge and understanding of the anatomy and the
      intricate relationships of each of the subsystems is essential for successful
      assessment and treatment. This paper presents a review of the anatomy,
      biomechanics and the integrated function of the glenohumeral joint which are
      essential for motion. The principles of rehabilitation of dynamic control of the
      glenohumeral joint are introduced.

PMID- 10903582
TI  - Lumbar spine traction: evaluation of effects and recommended application for
      treatment.
AB  - Despite the widespread use of traction, little is known of the mode of effect,
      and application remains largely anecdotal. The efficacy of traction is also
      unclear because of generally poor design of the clinical trials to date, and
      because subgroups of patients most likely to benefit have not been specifically
      studied. These observations prompted this review, the purposes of which are to
      evaluate the mechanisms by which traction may provide benefit and to provide
      rational guidelines for the clinical application of traction. Traction has been
      shown to separate the vertebrae and it appears that large forces are not
      required. Vertebral separation could provide relief from radicular symptoms by
      removing direct pressure or contact forces from sensitised neural tissue. Other
      mechanisms proposed to explain the effects of traction (e.g. reduction of disc
      protrusion or altered intradiscal pressure) have been shown not to occur. We
      conclude that traction is most likely to benefit patients with acute (less than 6
      weeks' duration) radicular pain with concomitant neurological deficit. The
      apparent lack of a dose-response relationship suggests that low doses are
      probably sufficient to achieve benefit.

PMID- 10903584
TI  - Clinical tests of the sacroiliac joint.
AB  - In the literature many tests are described which are designed to provoke pain or
      detect joint mobility in the sacroiliac joint (SIJ). However, in part 1 of this
      review, the authors stated that there is little evidence of reliability of these
      tests. In this article, the authors describe the methodological review of 11
      studies, which have dealt with the validity of SIJ tests. The methodological
      quality of the studies was tested by using a list of criteria that consisted of
      three categories: 1) study population, 2) test procedure and 3) test results. A
      weighting for each criterion was developed. The methodological score for the
      studies was, in general, disappointing and looked promising for only two out of
      11 studies (58 and 64 points). Four authors drew conclusions of positive validity
      from the tests they studied but other authors did not confirm these results. The
      conclusion of this methodological review is that there is no evidence to support
      the inclusion of mobility and pain provocation tests for the SIJ in clinical
      practice. Three major problems have been identified in validating SIJ dysfunction
      tests. Firstly, poor reliability of SIJ dysfunction tests exists, which may be
      improved by multiple test scores as postulated in part 1 of this review.
      Secondly, the methodological quality of validity studies needs to be developed to
      a much higher level with special consideration paid to sensitivity, specificity,
      confidence intervals and likelihood ratio values. And finally, there is a need
      for the proper use of a gold standard in assessing the validity of SIJ tests.

PMID- 10903583
TI  - Reliability of cervical range of motion using the OSI CA 6000 spine motion
      analyser on asymptomatic and symptomatic subjects.
AB  - Cervical range of motion (ROM) is evaluated in both clinical and research
      settings. This study's purpose was to determine if ROM data obtained with the OSI
      CA 6000 Spine Motion Analyser (SMA) from asymptomatic and symptomatic cervical
      subjects were reliable within and between testers. Cervical ROM was measured in
      all three planes in 30 adult asymptomatic and 20 adult symptomatic subjects. A
      standardized protocol was used to fit each subject with the OSI SMA cervical
      hardware. Subjects were tested in a seated position with the trunk stabilized.
      Subjects performed four trials of each pain-free cervical motion during testing.
      The hardware was completely removed and replaced by the same tester and ROM
      trials in all three planes were repeated for intratester asymptomatic and
      symptomatic reliability. The same procedure was completed by a second tester for
      asymptomatic intratester and intertester reliability. Repeated measures analysis
      of variance and intraclass correlation coefficients (ICC [2,1 and 2 k]) were used
      to analyse intra- and intertester reliability data. Intratester ICCs were 0.85 or
      higher (except for flexion 0.76) for asymptomatic subjects and 0. 87 or higher
      (except for flexion 0.68) for symptomatic subjects for all motions. Intertester
      ICCs were 0.88 or higher for all motions. Standard error of measurements were
      less than 3.92 degrees for all motions. Measures of cervical spinal ROM obtained
      with the OSI SMA showed good intertester reliablity for all motions, and good
      intratester reliability for all motions with the exception of the motion of
      flexion for one of the examiners, which showed moderate reliability.

PMID- 10903585
TI  - Inter-examiner reliability in assessing passive intervertebral motion of the
      cervical spine.
AB  - Passive intervertebral motion of the cervical spine was assessed independently by
      two physical therapists. The therapists had equal backgrounds concerning
      education and clinical experience. Sixty-one patients seeking care for cervical
      problems at a private clinic were included in the study where three segments of
      the cervical spine and the mobility of the first rib were graded as stiff or not
      stiff. Data were analysed by percentage agreement and kappa coefficient which
      indicates inter-examiner reliability greater than expected by chance. Results
      demonstrated inter-examiner reliability of between 70 and 87% and kappa
      coefficients ranging between 0.28 and 0.43 considered to be only 'fair to
      moderate'.

PMID- 10903586
TI  - Adding compression to mobilization in a rehabilitation program after knee
      surgery. A preliminary clinical observational study.
AB  - The cyclical loading of cartilage, which occurs during normal use of an
      articulation, stimulates biosynthetic activity of the chondrocytes. Therefore
      functional stimulation may contribute to joint repair. In this study the
      researchers added mobilization with compression to a standardized rehabilitation
      program in patients recovering from intra-articular reconstructive surgery of the
      anterior cruciate ligament. Thirty patients were treated with a standardized
      physical therapy program following surgery. For half of the patients,
      mobilization under compression was added to this rehabilitation program. The knee
      flexion range of motion (FROM) was measured using a goniometer. Patients who
      received mobilizations with compression reached a pre-set goal of 130 degrees
      FROM after a mean of six treatment sessions, compared to 11 sessions in the
      control group. This rapid progression was characterized by a significantly
      greater increase of FROM during the first two treatment sessions. The explanation
      for this observed effect may lie in fast response processes which could include
      rheological changes in synovial fluid, enhanced exchange between synovial fluid
      and cartilage matrix or increased synovial turnover rather than complex metabolic
      phenomena. The faster recovery of the pre-set goal (130 degrees of FROM) in the
      group receiving mobilizations with compression, would appear to justify future
      clinical trials investigating the potential benefits of adding these techniques
      to current rehabilitation programs.

PMID- 10903588
TI  - Diary of events

PMID- 10903587
TI  - Total glenohumeral joint replacement: totally different situation.

PMID- 10903589
TI  - Bibliography.

PMID- 10903590
TI  - Protective effects of ischemic preconditioning for liver resection performed
      under inflow occlusion in humans.
AB  - OBJECTIVE: To determine whether ischemic preconditioning protects the human liver
      against a subsequent period of ischemia in patients undergoing hemihepatectomy,
      and to identify possible underlying protective mechanisms of ischemic
      preconditioning, such as inhibition of hepatocellular apoptosis. SUMMARY
      BACKGROUND DATA: Ischemic preconditioning is a short period of ischemia followed
      by a brief period of reperfusion before a sustained ischemic insult. Recent
      studies in rodents suggest that ischemic preconditioning is a simple and powerful
      protective modality against ischemic injury of the liver. The underlying
      mechanisms are thought to be related to downregulation of the apoptotic pathway.
      METHODS: Twenty-four patients undergoing hemihepatectomy for various reasons
      alternatively received ischemic preconditioning (10 minutes of ischemia and 10
      minutes of reperfusion) before transection of the liver performed under inflow
      occlusion for exactly 30 minutes. Liver wedge and Tru-cut biopsy samples were
      obtained at the opening of the abdomen and 30 minutes after the end of the
      hepatectomy. Serum levels of aspartate transferase, alanine transferase,
      bilirubin and prothrombin time were determined daily until discharge.
      Hepatocellular apoptosis was evaluated by in situ terminal deoxynucleotidyl
      transferase mediated d-UTP nick end-labeling (TUNEL) assay and electron
      microscopy. Caspase 3 and 8 activities were measured in tissue using specific
      fluorometric assays. RESULTS: Serum levels of aspartate transferase and alanine
      transferase were reduced by more than twofold in patients subjected to ischemic
      preconditioning versus controls. The analysis of a subgroup of patients with mild
      to moderate steatosis indicated possible increased protective effects of ischemic
      preconditioning. In situ TUNEL staining demonstrated a dramatic reduction in the
      number of apoptotic sinusoidal lining cells in the ischemic preconditioning
      group. Electron microscopy confirmed features of apoptosis present in control but
      not in ischemic preconditioning patients. There was no significant difference in
      caspase 3 and 8 activity when patients with ischemic preconditioning were
      compared with controls. CONCLUSIONS: Ischemic preconditioning is a simple and
      effective modality protecting the liver against subsequent prolonged periods of
      ischemia. This strategy may be a more attractive technique than intermittent
      inflow occlusion, which is associated with increased blood loss during each
      period of reperfusion.

PMID- 10903591
TI  - Preconditioning for protection from ischemic injury: discriminating cause from
      effect from epiphenomenon.

PMID- 10903593
TI  - Percutaneous necrosectomy and sinus tract endoscopy in the management of infected
      pancreatic necrosis: an initial experience.
AB  - OBJECTIVE: To describe the development of a minimally invasive technique aimed at
      surgical debridement in addition to simple drainage of the abscess cavity.
      SUMMARY BACKGROUND DATA: Surgical intervention for secondary infection of
      pancreatic necrosis is associated with a death rate of 25% to 40%. Although
      percutaneous approaches may drain the abscess, they have often failed in the long
      term as a result of inability to remove the necrotic material adequately.
      METHODS: Fourteen consecutive patients with infected necrosis secondary to acute
      pancreatitis were studied. The initial four patients underwent sinus tract
      endoscopy along a drainage tract for secondary sepsis after prior open
      necrosectomy. This technique was then modified to allow primary debridement for
      proven sepsis to be carried out percutaneously in a further 10 patients. The
      techniques and initial results are described. RESULTS: Additional surgery for
      sepsis was successfully avoided in the initial four patients managed by sinus
      tract endoscopy, and none died. Of the following 10 patients managed by
      percutaneous necrosectomy, 2 died. The median inpatient stay was 42 days. There
      was one conversion for intraoperative bleeding. Eight patients recovered and were
      discharged from the hospital after a median of three percutaneous explorations.
      Only 40% of patients required intensive care management after surgery.
      CONCLUSIONS: These initial results in an unselected group of patients are
      encouraging and show that unlike with percutaneous or endoscopic techniques, both
      resolution of sepsis and adequate necrosectomy can be achieved. The authors'
      initial impression of a reduction in postoperative organ dysfunction is
      particularly interesting; however, the technique requires further evaluation in a
      larger prospective series.

PMID- 10903592
TI  - Management of hilar cholangiocarcinoma: comparison of an American and a Japanese
      experience.
AB  - OBJECTIVE: To compare the experience and outcome in the management of hilar
      cholangiocarcinoma at one American and one Japanese medical center. SUMMARY
      BACKGROUND DATA: Controversies surround the issues of extent of resection for
      hilar cholangiocarcinoma and whether the histopathology of such cancers are
      similar between patients treated in America and in Japan. METHODS: Records were
      reviewed of 100 patients treated between 1980 and 1995 at the Lahey Clinic in the
      United States, and of 155 patients treated between 1977 and 1995 at Nagoya
      University Hospital in Japan. Selected pathologic slides of resected cancers were
      exchanged between the two institutions and reviewed for diagnostic concordance.
      RESULTS: In the Lahey cohort, there were 25 resections, 53 cases of surgical
      exploration with biliary bypass or intubation, and 22 cases of percutaneous
      transhepatic biliary drainage or endoscopic biliary drainage without surgery. In
      the Nagoya cohort, the respective figures were 122, 10, and 23. The overall 5
      year survival rate of all patients treated (surgical and nonsurgical) during the
      study periods was 7% in the Lahey cohort and 16% in the Nagoya cohort. The
      overall 10-year survival rates were 0% and 12%, respectively. In patients who
      underwent resection with negative margins, the 5- and 10-year survival rates were
      43% and 0% for the Lahey cohort and 25% and 18% for the Nagoya cohort. The
      surgical death rate for patients undergoing resection was 4% for Lahey patients
      and 8% for Nagoya patients. Of the patients who underwent resection, en bloc
      caudate lobectomy was performed in 8% of the Lahey patients and 89% of the Nagoya
      patients. Histopathologic examination of resected cancers showed that the Nagoya
      patients had a higher stage of disease than the Lahey patients. CONCLUSIONS: In
      both Lahey and Nagoya patients, survival was most favorable when resection of
      hilar cholangiocarcinoma was accomplished with margin-negative resections.
      Combined bile duct and liver resection with caudate lobectomy contributed to a
      higher margin-negative resection rate in the Nagoya cohort.

PMID- 10903594
TI  - Patterns of recurrence and survival after laparoscopic and conventional
      resections for colorectal carcinoma.
AB  - OBJECTIVE: To determine whether survival and recurrence after laparoscopic
      assisted surgery for colorectal cancer is compromised by an initial laparoscopic
      approach. SUMMARY BACKGROUND DATA: Laparoscopic colorectal resection for
      malignancy remains controversial 8 years after its first description. Fears
      regarding compromised oncologic principles and early recurrence (particularly the
      phenomenon of port-site metastases) have tempered enthusiasm for this approach.
      Long-term follow-up data are at present scarce. METHODS: A prospective
      comparative trial was undertaken between December 1993 and May 1996, during which
      114 patients had laparoscopic-assisted resection by a single laparoscopic
      colorectal surgeon or conventional open surgery by a second specialist colorectal
      surgeon. Intensive follow-up for at least 2 years is available on 109 patients.
      Analysis was performed on an intention-to-treat basis. RESULTS: Recurrent disease
      has developed in 27 patients (25%), 16 of 57 in the laparoscopic group (28%) and
      11 of 52 in the conventional group (21%). Crude death rates are 26/57 (46%) in
      the laparoscopic group and 24/52 (46%) in the conventional group. No port-site
      metastases have occurred; however, wound metastases associated with disseminated
      disease have developed in three patients in the open group and one in the
      laparoscopic group. Stage-for-stage survival and recurrence figures are
      comparable. CONCLUSION: Oncologic outcome at a minimum of 2 years is not
      compromised by the laparoscopic approach. Wound recurrences are a feature of
      laparoscopic and conventional surgery for advanced disease.

PMID- 10903595
TI  - Thoracoscopic removal of intrathoracic neurogenic tumors: a combined Chinese
      experience.
AB  - OBJECTIVE: To review the surgical and clinical results of minimally invasive
      resection of intrathoracic neurogenic tumors using a video-assisted thoracoscopic
      technique. SUMMARY BACKGROUND DATA: Thoracoscopy has emerged as a possible means
      for diagnosing and managing various intrathoracic disorders. Benign intrathoracic
      tumors often are ideal lesions for resection using a video-assisted technique.
      The authors report on their combined experience with the thoracoscopic resection
      of 143 intrathoracic neurogenic tumors. METHODS: Between March 1992 and February
      1999, 143 patients with intrathoracic neurogenic tumors were diagnosed and
      underwent resection using video-assisted thoracoscopic techniques in three
      teaching centers. Case selection, surgical technique, and clinical results were
      reviewed. RESULTS: The average age of the patients was 40.8 years; 57.3% were
      male. Thirty-eight patients (27%) had symptoms attributable to the masses.
      Seventy-two masses were neurofibromas, 33 were neurilemmomas, 7 were
      paragangliomas, and 31 were ganglioneuromas. All but seven tumors were located in
      the posterior mediastinum. The masses were on average 3.5 cm in greatest
      diameter. The mean surgical time was 40 minutes, and the average hospital stay
      was 4.1 days. There were no major postoperative complications or recurrences to
      date. Nine patients reported paresthesias over the chest wall during a mean
      follow-up of 29 months. CONCLUSIONS: Resection of intrathoracic neurogenic tumors
      using a thoracoscopic technique based on standard surgical indications would seem
      to be appropriate. Most of these masses are benign and readily removed. For
      dumbbell tumors, a combined thoracic and neurosurgical approach is mandatory.

PMID- 10903596
TI  - Management of duodenal perforation after endoscopic retrograde
      cholangiopancreatography and sphincterotomy.
AB  - OBJECTIVE: To evaluate the authors' experience with periduodenal perforations to
      define a systematic management approach. SUMMARY BACKGROUND DATA: Traditionally,
      traumatic and atraumatic duodenal perforations have been managed surgically;
      however, in the last decade, management has shifted toward a more selective
      approach. Some authors advocate routine nonsurgical management, but the reported
      death rate of medical treatment failures is almost 50%. Others advocate mandatory
      surgical exploration. Those who favor a selective approach have not elaborated
      distinct management guidelines. METHODS: A retrospective chart review at the
      authors' medical center from June 1993 to June 1998 identified 14 instances of
      periduodenal perforation related to endoscopic retrograde
      cholangiopancreatography (ERCP), a rate of 1.0%. Charts were reviewed for the
      following parameters: ERCP findings, clinical presentation of perforation,
      diagnostic methods, time to diagnosis, radiographic extent and location of
      duodenal leak, methods of management, surgical procedures, complications, length
      of stay, and outcome. RESULTS: Fourteen patients had a periduodenal perforation.
      Eight patients were initially managed conservatively. Five of the eight patients
      recovered without incident. Three patients failed nonsurgical management and
      required extensive procedures with long hospital stays and one death. Six
      patients were managed initially by surgery, with one death. Each injury was
      evaluated for location and radiographic extent of leak and classified into types
      I through IV. CONCLUSIONS: Clinical and radiographic features of ERCP-related
      periduodenal perforations can be used to stratify patients into surgical or
      nonsurgical cohorts. A selective management scheme is proposed based on the
      features of each type.

PMID- 10903597
TI  - Enteral vitamin B12 supplements reverse postgastrectomy B12 deficiency.
AB  - OBJECTIVE: To examine the development of chemical and clinical vitamin B12
      deficiency after total gastrectomy, and to evaluate the efficacy of supplemental
      oral B12 administration. SUMMARY BACKGROUND DATA: Postgastrectomy anemia is due
      to deficiencies of iron and vitamin B12, and parenteral B12 administration is the
      only appropriate treatment. However, no guidelines exist for the prophylactic use
      of B12 in patients who undergo total gastrectomy, the clinical presentation of
      B12 deficiency in this context has not been defined, and the question of whether
      oral B12 administration can be used to prevent and treat B12 deficiency has not
      been examined. METHODS: Serum B12 concentrations were measured in 31 patients who
      had undergone total gastrectomy. Symptoms related to B12 deficiency were surveyed
      in detail. Serum B12 concentrations were measured every 6 months after total
      gastrectomy in 10 patients. Thirty one patients received supplemental B12: 18
      patients orally and 13 by intramuscular injection. RESULTS: The B12 concentration
      dropped below the lower limit of normal (200 pg/mL) for the first time in two
      patients at 1 year, in four patients at 2 years, in three patients at 3 years,
      and in one patient at 4 years. Seventy-eight percent of patients reported some
      symptoms related to B12 deficiency. The serum B12 concentration in patients who
      received supplemental B12 orally increased rapidly and all symptoms resolved with
      oral therapy alone. CONCLUSIONS: B12 deficiency can develop as early as 1 year
      after total gastrectomy and causes symptoms. Because enteral B12 treatment
      increases the serum B12 concentration and leads to rapid resolution of symptoms,
      it should be prescribed routinely to patients undergoing total gastrectomy.

PMID- 10903598
TI  - Effect of endotoxin on opossum gallbladder motility: a model of acalculous
      cholecystitis.
AB  - OBJECTIVE: To determine whether endotoxin causes histologic changes in the
      gallbladder consistent with acalculous cholecystitis, and to determine the
      effects of endotoxin on gallbladder motility. SUMMARY BACKGROUND DATA: Acute
      acalculous cholecystitis is frequently seen in critically ill, septic patients,
      after prolonged fasting and gallbladder stasis. The pathogenesis of acalculous
      cholecystitis is unknown; however, previous studies have suggested that ischemia
      may play a role. METHODS: Adult opossums received Escherichia coli
      lipopolysaccharide. The gallbladder was removed for histologic examination or for
      physiologic studies 4 hours to 2 weeks later. For histologic examination,
      gallbladder strips underwent standard hematoxylin-and-eosin processing. For
      physiologic studies, they were mounted in a tissue bath to determine responses to
      cholecystokinin octapeptide or electrical field stimulation. RESULTS: Intravenous
      endotoxin at a dose of 0.005 mg/kg resulted in disrupted mucosal surfaces and
      areas of hemorrhage; higher doses of endotoxin resulted in coagulation necrosis,
      hemorrhage, areas of fibrin deposition, and extensive mucosal loss, consistent
      with an acute ischemic insult. Endotoxin abolished the contractile response to
      cholecystokinin octapeptide in gallbladder strips 4 hours after endotoxin
      administration. The 0.005-mg/kg dose of endotoxin decreased the contractile
      response to cholecystokinin octapeptide for up to 96 hours after endotoxin
      administration and decreased the contractile response to electrical field
      stimulation for 48 hours after administration. Inhibition of nitric oxide
      synthase reversed the decreased contractile response to cholecystokinin
      octapeptide. CONCLUSIONS: Endotoxin causes an ischemic insult to the gallbladder
      similar to that seen in acalculous cholecystitis. Also, endotoxin may lead to
      gallbladder stasis by decreasing gallbladder contractile responses to hormonal
      and neural stimuli.

PMID- 10903599
TI  - Bactericidal/permeability-increasing protein preserves leukocyte functions after
      major liver resection.
AB  - OBJECTIVE: To analyze postoperative leukocyte functions in patients undergoing
      hemihepatectomy, and to assess the effect of treatment with the endotoxin
      neutralizing agent bactericidal/permeability-increasing protein (rBPI21). SUMMARY
      BACKGROUND DATA: Extensive liver resection is associated with a high incidence of
      infectious complications. Because elimination of pathogenic microorganisms occurs
      mainly by leukocytes, this increased rate of infections is most likely due to an
      impaired function of these cells. Endotoxin, translocated from the gut into the
      systemic circulation as a result of increased gut permeability and reduced
      hepatic clearance function after major liver resection, may play an important
      role in the impairment of posthepatectomy leukocyte function. METHODS: To
      investigate whether hemihepatectomy results in impaired leukocyte functions and
      to determine the role of endotoxin in this process, leukocyte oxidative burst and
      leukocyte antigen expression were studied in three groups of patients: patients
      undergoing a hemihepatectomy and receiving rBPI21 treatment, patients undergoing
      hemihepatectomy and receiving placebo, and as an extra control group patients
      undergoing other major abdominal surgeries. Blood samples were collected before
      surgery, 2 hours after surgery, and at days 1, 2, 5, and 7. Phorbol myristate
      acetate-stimulated oxidative burst was measured using dihydrorhodamine, and
      leukocyte surface expression of the antigens CD11b, CD16, and CD14 was
      investigated by indirect immunofluorescence. Both oxidative burst and membrane
      surface expression were quantified by flow cytometry. An indication of the
      antiendotoxin effect of rBPI21 treatment was provided by assessment of plasma
      lipopolysaccharide binding protein (LBP) levels by enzyme-linked immunosorbent
      assay. RESULTS: The oxidative burst in the hemihepatectomized patients receiving
      placebo and the controls increased 2 hours after surgery, whereas it decreased in
      the rBPI21-treated patients, resulting in significant differences between the
      groups. On day 1, neutrophil CD11b expression and monocyte CD14 expression in the
      rBPI21-treated patients and controls were significantly lower than in the placebo
      group. At 2 hours, CD16 expression in the placebo-treated patients was
      significantly higher than in the rBPI21-treated patients and controls. On day 5
      and day 7, plasma LBP levels were significantly higher in the placebo-treated
      patients compared with the rBPI21-treated patients. CONCLUSIONS: The results of
      this study show that patients undergoing major liver resection have an increased
      activation of leukocytes compared with those undergoing other major abdominal
      surgery. This enhanced activation may contribute to the increased risk of
      infection in these patients. Administration of the endotoxin-neutralizing agent
      rBPI21 to hemihepatectomy patients was shown to reduce plasma LBP levels, to
      preserve leukocyte functions partially, and to reduce leukocyte activation to the
      level of other, nonhepatic abdominal surgery.

PMID- 10903600
TI  - A comparative study of the elective treatment of variceal hemorrhage with beta
      blockers, transendoscopic sclerotherapy, and surgery: a prospective, controlled,
      and randomized trial during 10 years.
AB  - OBJECTIVE: To compare three options for the elective treatment of portal
      hypertension during a 10-year period. METHODS: Patients included in the trial
      were 18 to 76 years old, had a history of bleeding portal hypertension, and had
      undergone no prior treatment. Treatment options were beta-blockers (propranolol),
      sclerotherapy, and portal blood flow-preserving procedures (selective shunts and
      the Sugiura-Futagawa operation). RESULTS: A total of 119 patients were included:
      40 in the pharmacology group, 46 in the sclerotherapy group,and 33 in the
      surgical group. The three groups showed no differences in terms of age, Child
      Pugh classification, and cause of liver disease. The rebleeding rate was
      significantly lower in the surgical group than in the other two groups. The
      rebleeding rate was only 5% in the Child A surgical group, compared with 71% and
      68% for the sclerotherapy and pharmacotherapy groups, respectively. Survival was
      better for the low-risk patients (Child A) in the three groups, but when the
      three options were compared, no significant difference was found. CONCLUSIONS:
      Portal blood flow-preserving procedures offer the lowest rebleeding rate in low
      risk patients undergoing elective surgery.

PMID- 10903601
TI  - The quality of early-stage breast cancer care.
AB  - OBJECTIVE: To assess whether recent practice has improved, the authors created
      detailed, evidence-based guidelines and assessed the quality of early-stage
      breast cancer care at four hospitals in the metropolitan New York area. SUMMARY
      BACKGROUND DATA: Adjuvant treatments for early-stage breast cancer have been
      shown to improve health and longevity. However, reports from the 1980s showed
      marked underuse of these therapies. METHODS: All 723 women with early-stage
      breast cancer who had a definitive surgical procedure at four participating
      hospitals in the Mount Sinai-NYU Health System between April 1994 and August 1996
      were included. Inpatient and outpatient records were abstracted. RESULTS: Fifty
      nine percent of women underwent breast-conserving surgery, of whom 81% received
      radiation therapy. Hospital-specific radiation therapy rates varied from 69% to
      87%. Seventy-eight percent of women with stage 1B or greater cancer received
      systemic treatment, with hospital-specific rates varying from 71% to 86%. Between
      18% and 33% of women who could have benefited from local or systemic adjuvant
      treatments did not receive them. The risk of not getting a beneficial adjuvant
      treatment varied more than twofold by the hospital where the breast cancer
      surgery was performed. CONCLUSIONS: The hospital where breast cancer surgery is
      performed is associated with the likelihood that women receive effective local
      and systemic adjuvant treatments. Surgeons and members of hospital quality
      improvement programs should encourage multidisciplinary approaches to breast
      cancer care.

PMID- 10903602
TI  - Improvement in the results of surgical treatment of advanced squamous esophageal
      carcinoma during 15 consecutive years.
AB  - OBJECTIVE: To document the clinicopathologic characteristics and survival of
      patients undergoing esophagectomy for squamous carcinoma of the thoracic
      esophagus, and to examine the factors contributing to improvements in outcome
      noted in patients with advanced carcinoma. SUMMARY BACKGROUND DATA: Japanese and
      some Western surgeons recently have reported that radical esophagectomy with
      extensive lymphadenectomy conferred a survival advantage to patients with
      esophageal carcinoma. The factors contributing to this improvement in results
      have not been well defined. METHODS: From 1981 to 1995, 419 patients with
      carcinoma of the thoracic esophagus underwent esophagectomy at the Keio
      University Hospital. The clinicopathologic characteristics and survival of
      patients treated between 1981 and 1987 were compared with those of patients
      treated between 1988 and 1995. Multivariate analysis using the Cox regression
      model was carried out to evaluate the impact of 15 variables on survival of
      patients with p stage IIa to IV disease. Several variables related to prognosis
      were examined to identify differences between the two time periods. RESULTS: The
      5-year survival rate for all patients was 40.0%. The 5-year survival rate was
      17.7% for p stage IIa to IV patients treated during the earlier period and 37.6%
      for those treated during the latter period. The Cox regression model revealed
      seven variables to be important prognostic factors. Of these seven, three
      (severity of postoperative complications, degree of residual tumor, and number of
      dissected mediastinal nodes) were found to be significantly different between the
      earlier and latter periods. CONCLUSIONS: The survival of patients undergoing
      surgery for advanced carcinoma (p stage IIa to IV) of the thoracic esophagus has
      improved during the past 15 years. The authors' data suggest that this
      improvement is due mainly to advances in surgical technique and perioperative
      management.

PMID- 10903603
TI  - Incidence of tracheal stenosis and other late complications after percutaneous
      tracheostomy.
AB  - OBJECTIVE: To determine the incidence of tracheal stenosis, voice and breathing
      changes, and stomal complications after percutaneous dilatational tracheostomy
      (PDT). METHODS: From December 1992 through June 1999, 420 critically ill patients
      underwent 422 PDTs. There were 340 (81%) long-term survivors, 100 (29%) of whom
      were interviewed and offered further evaluation by fiberoptic laryngotracheoscopy
      (FOL) and tracheal computed tomography (CT). Tracheal stenosis was defined as
      more than 10% tracheal narrowing on transaxial sections or coronal and sagittal
      reconstruction views. Forty-eight patients agreed to CT evaluation; 38 patients
      also underwent FOL. CT and FOL evaluations occurred at 30 +/- 25 (mean +/-
      standard deviation) months after PDT. RESULTS: Twenty-seven (27%) patients
      reported voice changes and 2 (2%) reported persistent severe hoarseness. Vocal
      cord abnormalities occurred in 4/38 (11%) patients, laryngeal granuloma in 1 (3%)
      patient, focal tracheal mucosal erythema in 2 (5%) patients, and severe
      tracheomalacia/stenosis in 1 (2.6%) patient. CT identified mild (11-25%) stenosis
      in 10 (21%) asymptomatic patients, moderate (26-50%) stenosis in 4 (8.3%)
      patients, 2 who were symptomatic, and severe (>50%) stenosis in 1 (2%)
      symptomatic patient. Ten patients (10%) reported persistent respiratory problems
      after tracheal decannulation, but only four agreed to be studied. Two patients
      had moderate stenosis, and one had severe stenosis. One patient's CT scan was
      normal. No long-term stomal complications were identified or reported.
      CONCLUSIONS: Subjective voice changes and tracheal abnormalities are common after
      endotracheal intubation followed by PDT. Long-term follow-up of critically ill
      patients identified a 31% rate of more than 10% tracheal stenosis after PDT.
      Symptomatic stenosis manifested by subjective respiratory symptoms after
      decannulation was found in 3 of 48 (6%) patients.

PMID- 10903604
TI  - Multifactorial risk index for predicting postoperative respiratory failure in men
      after major noncardiac surgery. The National Veterans Administration Surgical
      Quality Improvement Program.
AB  - OBJECTIVE: To develop and validate a preoperative risk index for predicting
      postoperative respiratory failure (PRF). SUMMARY BACKGROUND DATA: Respiratory
      failure is an important postoperative complication. METHOD: Based on a
      prospective cohort study, cases from 44 Veterans Affairs Medical Centers (n =
      81,719) were used to develop the models. Cases from 132 Veterans Affairs Medical
      Centers (n = 99,390) were used as a validation sample. PRF was defined as
      mechanical ventilation for more than 48 hours after surgery or reintubation and
      mechanical ventilation after postoperative extubation. Ventilator-dependent,
      comatose, do not resuscitate, and female patients were excluded. RESULTS: PRF
      developed in 2,746 patients (3.4%). The respiratory failure risk index was
      developed from a simplified logistic regression model and included abdominal
      aortic aneurysm repair, thoracic surgery, neurosurgery, upper abdominal surgery,
      peripheral vascular surgery, neck surgery, emergency surgery, albumin level less
      than 30 g/L, blood urea nitrogen level more than 30 mg/dL, dependent functional
      status, chronic obstructive pulmonary disease, and age. CONCLUSIONS: The
      respiratory failure risk index is a validated model for identifying patients at
      risk for developing PRF and may be useful for guiding perioperative respiratory
      care.

PMID- 10903605
TI  - Comparison of intravenous/oral ciprofloxacin plus metronidazole versus
      piperacillin/tazobactam in the treatment of complicated intraabdominal
      infections.
AB  - OBJECTIVE: To compare the safety and efficacy of intravenous (IV) ciprofloxacin
      plus IV metronidazole (CIP+MET) with that of IV piperacillin/tazobactam
      (PIP/TAZO) in adults with complicated intraabdominal infections, and to compare
      the efficacy of sequential IV-to-oral CIP+MET therapy with that of the IV CIP
      only regimen. SUMMARY BACKGROUND DATA: Treatment of intraabdominal infections
      remains a challenge, mainly because of their polymicrobial etiology and attendant
      death and complications. Antimicrobial regimens using sequential IV-to-oral
      therapy may reduce the length of hospital stay. METHODS: In this multicenter,
      randomized, double-blind trial involving 459 patients, clinically improved IV
      treated patients were switched to oral therapy after 48 hours. Overall clinical
      response was the primary efficacy measurement. RESULTS: A total of 282 patients
      (151 CIP+MET, 131 PIP/TAZO) were valid for efficacy. Of these patients, 64%
      CIP+MET and 57% PIP/TAZO patients were considered candidates for oral therapy.
      Patients had a mean APACHE II score of 9.6. The most common diagnoses were
      appendicitis (33%), other intraabdominal infection (29%), and abscess (25%).
      Overall clinical resolution rates were statistically superior for CIP+MET (74%)
      compared with PIP/TAZO (63%). Corresponding rates in the subgroup suitable for
      oral therapy were 85% for CIP+MET and 70% for PIP/TAZO. Postsurgical wound
      infection rates were significantly lower in CIP+MET (11%) versus PIP/TAZO
      patients (19%). Mean length of stay was 14 days for CIP+MET and 17 days for
      PIP/TAZO patients. CONCLUSION: CIP+MET, initially administered IV and followed by
      CIP+MET oral therapy, was clinically more effective than IV PIP/TAZO for the
      treatment of patients with complicated intraabdominal infections.

PMID- 10903606
TI  - Accelerated rejection of renal allografts from brain-dead donors.
AB  - OBJECTIVE: To define the potential influences of donor brain death on organs used
      for transplantation. SUMMARY BACKGROUND DATA: Donor brain death causes prompt
      upregulation of inflammatory mediators on peripheral organs. It is hypothesized
      that this antigen-independent insult may influence the rate and intensity of host
      alloresponsiveness after engraftment. METHODS: The rates of survival of
      unmodified Lew recipients sustained by kidney allografts from brain-dead, normal
      anesthetized, and anesthetized ventilated F344 donors were compared. Brain death
      was induced by gradually increasing intracranial pressure under
      electroencephalographic control. Tracheotomized brain-dead animals and
      anesthetized controls were mechanically ventilated for 6 hours before transplant
      nephrectomy. The rate and intensity of the acute rejection event were examined by
      histology, immunohistology, and reverse transcriptase-polymerase chain reaction.
      RESULTS: Animals bearing kidneys from brain-dead donors died of renal failure
      secondary to acute rejection at a significantly faster rate than those from
      anesthetized living controls or anesthetized animals ventilated for 6 hours.
      Within 3 hours after placement and reperfusion of brain-dead donor grafts,
      significant neutrophil infiltration was observed, followed by increasing numbers
      of macrophages and T cells. mRNA of proinflammatory mediators detected in kidneys
      within 6 hours of brain death and upregulated even before transplantation
      increased thereafter and appeared to accelerate and amplify host
      alloresponsiveness, as manifested by the rapid expression of chemokines,
      cytokines, adhesion molecules, and major histocompatibility complex class II
      antigens in the engrafted organ. The process evolved in the controls less
      intensely and at a slower rate. CONCLUSIONS: Donor brain death is a significant
      risk factor for peripheral organs used for transplantation. The activated state
      of such organs appears to trigger host immune mechanisms that accelerate the
      process of acute rejection. The effects of this central injury may explain in
      part the less satisfactory performance of cadaver organs in human transplantation
      compared with those from living sources.

PMID- 10903607
TI  - Activated protein C reduces the ischemia/reperfusion-induced spinal cord injury
      in rats by inhibiting neutrophil activation.
AB  - OBJECTIVE: To examine whether activated protein C (APC) reduces spinal cord
      injury in rats by inhibiting neutrophil activation after the transient ischemia.
      SUMMARY BACKGROUND DATA: Ischemic spinal cord injury is an important pathologic
      mechanism leading to the paraplegia observed after surgery to repair aortic
      aneurysms. Activated neutrophils play a pivotal role in the development of
      ischemia/reperfusion-induced tissue injury. Recently, the authors have reported
      that APC, a physiologic anticoagulant, prevents lipopolysaccharide-induced
      pulmonary vascular injury by inhibiting neutrophil activation. These observations
      strongly suggest that APC reduces ischemia/reperfusion-induced spinal cord injury
      by inhibiting neutrophil activation. METHODS: In rats, spinal cord ischemia was
      induced by using a balloon catheter placed into the aorta. After the transient
      ischemia, survival and motor function were evaluated, and histologic examination
      of the spinal cord was performed by using both hematoxylin-and-eosin staining and
      2,3,5, -triphenyltetrazolium chloride (TTC) staining 24 hours after the ischemia.
      Tissue levels of myeloperoxidase and cytokines, including tumor necrosis factor
      alpha (TNF-alpha) and rat interleukin-8, were measured in six experimental
      groups: sham-operated, control, APC (100 microg/kg, intravenous), dansyl glutamyl
      glycyl-arginyl chloromethyl ketone-treated activated factor X (DEGR-F.Xa), a
      selective inhibitor of thrombin generation (1 mg/kg, intravenous), nitrogen
      mustard-induced leukocytopenia, and diisopropyl fluorophosphate-treated APC (DIP
      APC), active site-blocked APC (100 microg/kg, intravenous). APC, DEGR-F.Xa, and
      DIP-APC were administered intravenously 30 minutes before aortic occlusion.
      Control and leukocytopenic rats received saline instead of other drugs. RESULTS:
      Pretreatment with APC significantly reduced motor disturbances compared with
      those in control animals. In contrast, neither DEGR-F.Xa nor DIP-APC had any
      effect. Microinfarctions, evidenced by the absence of TTC staining and histologic
      change, were markedly reduced in animals given APC. The increases in the tissue
      levels of TNF-alpha, rat interleukin-8, and myeloperoxidase in the ischemic part
      of the spinal cord were significantly reduced in animals that received APC. These
      levels were not reduced in rats given DEGR-F.Xa or DIP-APC. Leukocytopenia
      produced effects similar to those of APC. CONCLUSIONS: APC reduced the
      ischemia/reperfusion-induced spinal cord injury by inhibiting neutrophil
      activation. The therapeutic mechanisms of APC might depend on its inhibitory
      effect on the production of TNF-alpha, which is a potent activator of
      neutrophils. Although the anticoagulant effects of APC might not be related to
      its ability to inhibit TNF-alpha production, its serine protease activity appears
      to be essential in the therapeutic mechanism. APC appears to have potential as a
      therapeutic agent for prevention of spinal cord injury in patients undergoing
      aortic aneurysm repair.

PMID- 10903608
TI  - Meralgia paresthetica, the elusive diagnosis: clinical experience with 14 adult
      patients.
AB  - OBJECTIVE: To discuss the diagnosis and treatment of meralgia paresthetica as
      reported in the literature and as experienced by the author. SUMMARY BACKGROUND
      DATA: Meralgia paresthetica is a mononeuropathy of the lateral femoral cutaneous
      nerve that can lead to significant disability when the diagnosis and treatment is
      delayed or missed. This condition is relatively common but is frequently mistaken
      for other disorders. METHODS: Fifteen cases of meralgia paresthetica were
      identified in 14 patients in a private surgical practice during a 4-year period.
      All patients were initially treated conservatively and seven patients
      subsequently underwent surgical treatment. Follow-up ranged from 3 to 6 years.
      RESULTS: Conservative management consisting of local analgesics, steroids,
      nonsteroidal antiinflammatories, rest, and reduction or elimination of
      aggravating factors yielded long-lasting improvement in five patients with
      meralgia paresthetica. Nine patients with 10 cases of meralgia paresthetica did
      not benefit in the long term from conservative management. Seven of these
      patients, representing eight cases of meralgia paresthetica, ultimately opted for
      surgical management, and all obtained good long-term relief of symptoms.
      CONCLUSION: Surgical management of meralgia paresthetica is a viable option for
      patients in whom medical management fails. Based on the published literature and
      the author's experience, a rationale is presented for determining the appropriate
      surgical management of these patients.

PMID- 10903609
TI  - Use of health information systems in the Russian federation in the assessment of
      environmental health effects.
AB  - The Russian Federation has made an intensive effort to compile and use
      information on the environment and human health. In 1996-1997, we evaluated the
      information that was collected and analyzed on the local (raion), regional
      (oblast), and federal levels with reference to its usefulness in the assessment
      of environmental health effects. The Russian Federation maintains standardized
      nationwide institutions that routinely collect health data in polyclinics and
      hospitals and then report to the national offices. The allocations of the
      workforce and the broad range of surveyed health outcomes are extensive, but a
      lack of systematic control of information quality limits the ability to take full
      advantage of these efforts. On the other hand, the hierarchical system of data
      collection has advantages over more decentralized or commercial health systems. A
      major weakness in the current reporting is the aggregation and transformation of
      data. Although this may not disturb the generation of health statistics, it
      seriously limits the use of regional and federal level data in the assessment of
      health effects of environmental exposures. In spite of limitations, some revised
      approaches to the analysis of existing data may be both feasible and fruitful.
      Combining information from routine data and newly collected data is likely to be
      the most effective way to assess the relationship between environmental exposures
      and diseases. Although there is a strong and justifiable desire to rapidly
      translate information of environmental health effects into policy alternatives,
      at present, it seems more useful to emphasize data quality, completeness, and
      plans for the use of data.

PMID- 10903610
TI  - Excretion of hexachlorobenzene and metabolites in feces in a highly exposed human
      population.
AB  - A set of 53 individuals from a population highly exposed to airborne
      hexachlorobenzene (HCB) were selected to study the elimination kinetics of this
      chemical in humans. The volunteers provided blood, 24-hr urine, and feces samples
      for analysis of HCB and metabolites. The serum HCB concentrations ranged from 2.4
      to 1,485 ng/mL (mean +/- SD, 124 +/- 278), confirming that this human population
      has the highest HCB blood levels ever reported. All analyzed feces samples
      contained unchanged HCB (range, 11-3,025 ng/g dry weight; mean +/- SD, 395 +/-
      629). The HCB concentration in feces strongly correlated with HCB in serum (r =
      0.85; p < 0.001), suggesting an equilibrium in feces/serum that is compatible
      with a main pulmonary entrance of the chemical and low intestinal excretion of
      nonabsorbed foodborne HCB. The equilibrium is also compatible with a nonbiliary
      passive transfer of the chemical to the intestinal lumen. Two HCB main
      metabolites, pentachlorophenol (PCP) and pentachlorobenzenethiol (PCBT), were
      detected in 51% and 54% of feces samples, respectively. All urine samples
      contained PCP and PCBT, confirming the conclusions of a previous study [Environ
      Health Perspect 105:78-83 (1997)]. The comparison between feces and urine showed
      that whereas daily urinary elimination of metabolites may account for 3% of total
      HCB in blood, intestinal excretion of unchanged HCB may account for about 6%,
      thus showing the importance of metabolism in the overall elimination of HCB. The
      elimination of HCB and metabolites by both routes, however, appears to be very
      small (< 0.05%/day) as compared to the estimated HCB adipose depots. Features of
      HCB kinetics that we present in this study, i.e., nonsaturated intestinal
      elimination of HCB and excretion in feces and urine of inert glutathione
      derivatives, may explain, in part, the absence of porphyria cutanea in this human
      population heavily exposed to HCB.

PMID- 10903611
TI  - Occurrence of Tris(4-chlorophenyl)methane, tris(4-chlorophenyl)methanol, and some
      other persistent organochlorines in Japanese human adipose tissue.
AB  - Tris(4-chlorophenyl)methane (TCPMe) and tris(4-chlorophenyl)methanol (TCPMOH) are
      among the most recently identified environmental contaminants. Despite their
      widespread contamination in the marine environment, human exposure to these
      compounds remains relatively unknown. We determined the concentrations of TCPMe,
      TCPMOH, and other persistent organochlorines such as polychlorinated biphenyls
      (PCBs), DDT and its metabolites, hexachlorocyclohexane isomers,
      hexachlorobenzene, and chlordane compounds (CHLs) in human adipose tissue from
      Japan. TCPMe and TCPMOH were detected in all of the adipose samples analyzed; the
      concentrations ranged from 2.5-21 and 1.1-18 ng/g lipid weight, respectively.
      Concentrations of TCPMe and TCPMOH in humans were less than those reported in
      marine mammals, suggesting the possibility of metabolism and elimination of these
      compounds by humans. Significant correlation between TCPMe and TCPMOH with
      concentrations of DDT and its metabolites in human adipose tissues suggested that
      exposure to DDT is the source of TCPMe and TCPMOH in humans. The age- and sex
      dependent accumulation of TCPMe and TCPMOH as well as other organochlorines was
      less pronounced. Results for other organochlorines indicated that recent
      contamination status of PCBs in human samples from Japan was higher than that in
      developing countries, whereas DDT contamination is lower. Greater concentrations
      of CHLs in human adipose tissue from Japan than in those from other countries
      suggest that continuous monitoring of CHLs in humans in Japan is necessary. To
      our knowledge, this is the first study on the accumulation of TCPMe and TCPMOH in
      human adipose tissue.

PMID- 10903613
TI  - Analysis of hydroxylated metabolites of PCBs (OH-PCBs) and other chlorinated
      phenolic compounds in whole blood from Canadian inuit.
AB  - In this study, we identified the main hydroxylated polychlorinated biphenyls (OH
      PCBs) and other chlorinated phenolic compounds and we determined their relative
      concentrations in whole blood from 13 male and 17 female Inuit from northern
      Quebec, Canada, and from a pooled whole blood sample from southern Quebec. We
      also determined concentrations of polychlorinated biphenyls (PCBs). Total OH-PCB
      concentrations were variable among the Inuit samples, ranging over 2 orders of
      magnitude (0.117-11.6 ng/g whole blood wet weight). These concentrations were
      equal to and up to 70 times those found for the southern Quebec pooled whole
      blood sample. Geometric mean concentrations of total OH-PCBs were 1.73 and 1.01
      ng/g whole blood for Inuit men and women, respectively, and 0.161 ng/g whole
      blood for the southern population pool. There are limited data available for
      comparison, but the levels of OH-PCBs in Inuit are higher than those previously
      reported in the literature for other populations. There was a significant
      correlation (p < 0.005) between OH-PCBs and PCBs (r = 0.84) and both correlated
      significantly (p < 0.005) with age (r = 0.68 and 0.78, respectively). The ratio
      of OH-PCBs to PCBs was lower in Inuit (0.11) than in the southern Quebec pool
      (0.33). There is no apparent explanation for the difference. There was
      considerable variability in the congener pattern of the identified OH-PCBs. The
      main metabolite, 4-OH-CB109 (4-OH-2,3,3',4', 5-pentachlorobiphenyl), constituted
      12-62% of the total OH-PCBs in the samples. Pentachlorophenol (PCP) was the
      dominant phenolic compound in blood, constituting 46% (geometric mean) of the
      total quantitated chlorinated phenolic compounds. PCP concentrations in Inuit
      blood ranged from 0.558 to 7.77 ng/g on a wet weight basis. All but two Inuit
      samples had lower concentrations than the southern Quebec pool (6.29 ng/g). The
      possible role of OH-PCBs in mediating PCB-induced adverse effects needs to be
      investigated further.

PMID- 10903612
TI  - Microcystic cyanobacteria extract induces cytoskeletal disruption and
      intracellular glutathione alteration in hepatocytes.
AB  - Microcystins are a group of highly liver-specific toxins, although their exact
      mechanisms of action remain unclear. We examined the effects of microcystic
      cyanobacteria extract (MCE) collected from a contaminated water source on the
      organization of cellular microtubules (MTs) and microfilaments (MFs) in
      hepatocytes. We also investigated the effects on lactate dehydrogenase (LDH)
      leakage and intracellular glutathione (GSH). Primary cultured rat hepatocytes
      exposed to MCE (equivalent to 125 microg/mL lyophilized algae cells) showed a
      characteristic disruption of MTs and MFs in a time-dependent manner. Under these
      conditions, MCE caused aggregation of MTs and MFs and a severe loss of MTs in
      some cells. Moreover, MCE-induced cytoskeletal alterations preceded the LDH
      leakage. On the other hand, the treatment of cells with MCE led to a dose
      dependent increase of intracellular GSH. However, time-course study showed a
      biphasic change of intracellular GSH levels with a significant increase in the
      initial stage followed by a decrease after prolonged treatment. Furthermore,
      pretreatment with N-acetylcystein (NAC), a GSH precursor, significantly enhanced
      the intracellular GSH level and decreased the MCE-induced cytotoxicity as well as
      cytoskeleton changes. In contrast, buthionine-(S, R)-sulfoximine, a specific GSH
      synthesis inhibitor, increased the cell susceptibility to MCE-induced
      cytotoxicity by depleting the intracellular GSH level. These findings suggest
      that intracellular GSH plays an important role in MCE-induced cytotoxicity and
      cytoskeleton changes in primary cultured rat hepatocytes. Increasing
      intracellular GSH levels protect cells from MCE-induced cytotoxicity and
      cytoskeleton changes.

PMID- 10903614
TI  - Arsenic-induced skin lesions among Atacameno people in Northern Chile despite
      good nutrition and centuries of exposure.
AB  - It has been suggested that the indigenous Atacameno people in Northern Chile
      might be protected from the health effects of arsenic in drinking water because
      of many centuries of exposure. Here we report on the first intensive
      investigation of arsenic-induced skin lesions in this population. We selected 11
      families (44 participants) from the village of Chiu Chiu, which is supplied with
      water containing between 750 and 800 microg/L inorganic arsenic. For comparison,
      8 families (31 participants) were also selected from a village where the water
      contains approximately 10 microg/L inorganic arsenic. After being transported to
      the nearest city for blind assessment, participants were examined by four
      physicians with experience in studying arsenic-induced lesions. Four of the six
      men from the exposed village, who had been drinking the contaminated water for
      more than 20 years, were diagnosed with skin lesions due to arsenic, but none of
      the women had definite lesions. A 13-year-old girl had definite skin pigmentation
      changes due to arsenic, and a 19-year-old boy had both pigmentation changes and
      keratoses on the palms of his hands and the soles of his feet. Family interviews
      identified a wide range of fruits and vegetables consumed daily by the affected
      participants, as well as the weekly intake of red meat and chicken. However, the
      prevalence of skin lesions among men and children in the small population studied
      was similar to that reported with corresponding arsenic drinking water
      concentrations in both Taiwan and West Bengal, India--populations in which
      extensive malnutrition has been thought to increase susceptibility.

PMID- 10903616
TI  - Estradiol-type activity of coumestrol in mature and immature ovariectomized rat
      uterotrophic assays.
AB  - Makaverich et al. [Environ Health Perspect 103:574-581 (1995)] reported that the
      uterotrophic activity of the phytoestrogen coumestrol in the immature
      ovariectomized rat was atypical in that it was not associated with increased
      uterine hyperplasia and DNA content. We previously reported that coumestrol gave
      a typical estradiol-type uterotrophic response in the immature intact rat,
      yielding increases in uterine epithelial cell height, glandular formation, cell
      labeling, and DNA content. These papers did not answer the question of whether
      there is a basic difference between the ovariectomized and the intact rat
      uterotrophic assays. In this paper, we report that coumestrol gives a typical
      estradiol-type uterotrophic response in uterotrophic assays using immature
      intact, immature ovariectomized, and mature ovariectomized rats. We concluded
      that the uterotrophic activity of coumestrol is typical of the natural estrogen
      estradiol.

PMID- 10903615
TI  - Estrogenic activity assessment of environmental chemicals using in vitro assays:
      identification of two new estrogenic compounds.
AB  - Environmental chemicals with estrogenic activities have been suggested to be
      associated with deleterious effects in animals and humans. To characterize
      estrogenic chemicals and their mechanisms of action, we established in vitro and
      cell culture assays that detect human estrogen receptor [alpha] (hER[alpha])
      mediated estrogenicity. First, we assayed chemicals to determine their ability to
      modulate direct interaction between the hER[alpha] and the steroid receptor
      coactivator-1 (SRC-1) and in a competition binding assay to displace 17ss
      estradiol (E(2)). Second, we tested the chemicals for estrogen-associated
      transcriptional activity in the yeast estrogen screen and in the estrogen
      responsive MCF-7 human breast cancer cell line. The chemicals investigated in
      this study were o,p'-DDT (racemic mixture and enantiomers), nonylphenol mixture
      (NPm), and two poorly analyzed compounds in the environment, namely, tris-4
      (chlorophenyl)methane (Tris-H) and tris-4-(chlorophenyl)methanol (Tris-OH). In
      both yeast and MCF-7 cells, we determined estrogenic activity via the estrogen
      receptor (ER) for o,p'-DDT, NPm, and for the very first time, Tris-H and Tris-OH.
      However, unlike estrogens, none of these xenobiotics seemed to be able to induce
      ER/SRC-1 interactions, most likely because the conformation of the activated
      receptor would not allow direct contacts with this coactivator. However, these
      compounds were able to inhibit [(3)H]-E(2) binding to hER, which reveals a direct
      interaction with the receptor. In conclusion, the test compounds are estrogen
      mimics, but their molecular mechanism of action appears to be different from that
      of the natural hormone as revealed by the receptor/coactivator interaction
      analysis.

PMID- 10903617
TI  - Toxic evaluation of organic extracts from airborne particulate matter in Puerto
      Rico.
AB  - In recent years, several hypotheses have emerged to explain the toxicologic
      activity of particulate matter. Organic compounds, ultrafine particles, biologic
      components, and transition metals are some of the constituents that reportedly
      exert some type of adverse effect on human health. A considerable fraction of the
      urban particulate matter consists of carbon compounds, which originate mostly
      from anthropogenic sources. The toxicity of organic fractions from particulate
      matter have been mainly evaluated by considering their mutagenic activity. This
      research expands on the toxicologic profile of organic compounds adsorbed to
      particulate matter, specifically in Puerto Rico, by using the cytotoxic neutral
      red bioassay (NRB). The NRB uses normal human epidermal keratinocytes or other
      types of cells to measure the effect on cell viability when exposed to organic
      compounds associated to the particles in the air. We validated the NRB for
      particulate matter by using a standard reference material (SRM 1649). We used the
      NRB to determine toxicologic differences of extracts between an urban
      industrialized site with anthropogenic activity versus a coastal region with less
      human activity. The cytotoxicity associated with organic compounds in particulate
      matter collected at the urban industrialized site was detected in both the
      particulate matter (3/4) 10 microm in aerodynamic diameter (PM(10)) and
      particulate matter (3/4) 100 microm in aerodynamic diameter (PM(100)). Greater
      toxic effects were observed in PM(10) extracts than in PM(100) extracts, but
      PM(10) toxic effects were not significantly different from those in PM(100). The
      extracts from the industrialized site were more cytotoxic than the extracts from
      coastal reference site, although in the summer, extracts from both sites were
      significantly cytotoxic to normal human epidermal keratinocytes. In addition, the
      nonpolar extracts of both PM(10) and PM(100) exerted the greatest cytotoxicity,
      followed by the polar, and, finally, the moderately polar extract. This study
      demonstrates that extracts from the Guaynabo industrialized site were more toxic
      than similar extracts obtained from a reference coastal site in Fajardo, Puerto
      Rico.

PMID- 10903618
TI  - Long-term pyrene exposure of grass shrimp, Palaemonetes pugio, affects molting
      and reproduction of exposed males and offspring of exposed females.
AB  - The objective of this study was to investigate the impact of long-term pyrene
      exposure on molting and reproduction in the model estuarine invertebrate, the
      grass shrimp (Palaemonetes pugio). Grass shrimp were exposed to measured
      concentrations of 5.1, 15.0, and 63. 4 ppb (microg/L) pyrene for 6 weeks, during
      which time we determined molting and survivorship. At the end of the exposure, we
      immediately sacrificed some of the shrimp for biomarker (CYP1A and vitellin)
      analyses. The remaining shrimp were used to analyze fecundity and embryo
      survivorship during an additional 6 weeks after termination of pyrene exposure.
      Male shrimp at the highest pyrene dose (63 ppb) experienced a significant delay
      in molting and in time until reproduction, and showed elevated ethoxycoumarin o
      deethylase (ECOD) activity immediately after the 6-week exposure period. In
      contrast, 63 ppb pyrene did not affect these parameters in female shrimp. Females
      produced the same number of eggs per body weight, with high egg viability (98
      100%) at all exposure levels, but with decreased survival for the offspring of
      the 63-ppb pyrene-exposed females. In addition, vitellin levels were elevated
      only in females at 63 ppb pyrene after the 6-week exposure. We hypothesize that
      the elevated vitellin binds pyrene and keeps it biologically unavailable to adult
      females, resulting in maternal transfer of pyrene to the embryos. This would
      account for the lack of effect of pyrene exposure on ECOD activity, molting, and
      reproduction in the adult females, and for reduced survival of their offspring.

PMID- 10903619
TI  - Fecundability and parental exposure to ambient sulfur dioxide.
AB  - Recently it has been observed that birth rates in Teplice, a highly polluted
      district in Northern Bohemia, have been reduced during periods when sulfur
      dioxide levels were high. This study, which is based on data from 2,585 parental
      pairs in the same region, describes an analysis of the impact of SO(2) on
      fecundability in the first unprotected menstrual cycle (FUMC). We obtained
      detailed personal data, including time-to-pregnancy information, via maternal
      questionnaires at delivery. We estimated individual exposures to SO(2) in each of
      the 4 months before conception on the basis of continual central monitoring.
      Three concentration intervals were introduced: < 40 microg/m(3 )(reference
      level); 40-80 microg/m(3); and [greater than or equal to] 80 microg/m(3). We
      estimated adjusted odds ratios (AORs) of conception in the FUMC using logistic
      regression models. Many variables were screened for confounding. AORs for
      conception in the FUMC were consistently reduced only for couples exposed in the
      second month before conception to SO(2) levels as follows: 40-80 microg/m(3), AOR
      0.57 [95% confidence interval (CI), 0.37-0.88; p < 0.011]; [greater than or equal
      to] 80 microg/m(3), AOR 0.49 (CI, 0.29-0.81; p < 0.006). The association was
      weaker in the second 2 years of the study, probably due to the gradual decrease
      of SO(2) levels in the region. The relationship between SO(2) and fecundability
      was greater in couples living close to the central monitoring station (within 3.5
      km). The timing of these effects is consistent with the period of sperm
      maturation. This is in agreement with recent findings; sperm abnormalities
      originating during spermatid maturation were found in young men from Teplice
      region who were exposed to the increased levels of ambient SO(2). Alternative
      explanations of our results are also possible.

PMID- 10903620
TI  - Risk of internal cancers from arsenic in drinking water.
AB  - The U.S. Environmental Protection Agency is under a congressional mandate to
      revise its current standard for arsenic in drinking water. We present a risk
      assessment for cancers of the bladder, liver, and lung from exposure to arsenic
      in water, based on data from 42 villages in an arseniasis-endemic region of
      Taiwan. We calculate excess lifetime risk estimates for several variations of the
      generalized linear model and for the multistage-Weibull model. Risk estimates are
      sensitive to the model choice, to whether or not a comparison population is used
      to define the unexposed disease mortality rates, and to whether the comparison
      population is all of Taiwan or just the southwestern region. Some factors that
      may affect risk could not be evaluated quantitatively: the ecologic nature of the
      data, the nutritional status of the study population, and the dietary intake of
      arsenic. Despite all of these sources of uncertainty, however, our analysis
      suggests that the current standard of 50 microg/L is associated with a
      substantial increased risk of cancer and is not sufficiently protective of public
      health.

PMID- 10903621
TI  - Methods of exposure assessment: lead-contaminated dust in Philadelphia schools.
AB  - This study was conducted to develop a method that would accurately assess
      children's exposure to lead in schools in Philadelphia, Pennsylvania. We examined
      three wipe sample protocols: one included accessible surfaces such as desktops
      and windowsills, the second included inaccessible surfaces such as the top of
      filing cabinets and light fixtures, and the third included hand wipes of the
      study participants. Surface wipes were collected at 10 locations from accessible
      and inaccessible classroom surfaces (n = 11 at each location) and from the palms
      of student subjects in the same locations (n = 168). We found a significant
      difference in lead dust concentrations determined by the three protocols (F =
      4.619; 2,27 degrees of freedom; p = 0.019). Lead dust concentrations were
      significantly elevated at the inaccessible surfaces yet they were uniformly low
      on the accessible surfaces and the children's palms. These findings were
      consistent with observed changes in blood lead levels of study participants:
      after 6 months of exposure to the study locations, 156 of 168 children
      experienced no change in blood lead level, whereas 12 experienced only a minimal
      change of 1-2 microg/dL. The mere presence of lead in inaccessible dust in the
      school environment does not automatically constitute a health hazard because
      there may not be a completed exposure pathway.

PMID- 10903622
TI  - Chronic arsenic exposure and risk of infant mortality in two areas of Chile.
AB  - Chronic arsenic exposure has been associated with a range of neurologic,
      vascular, dermatologic, and carcinogenic effects. However, limited research has
      been directed at the association of arsenic exposure and human reproductive
      health outcomes. The principal aim of this study was to investigate the trends in
      infant mortality between two geographic locations in Chile: Antofagasta, which
      has a well-documented history of arsenic exposure from naturally contaminated
      water, and Valparaiso, a comparable low-exposure city. The arsenic concentration
      in Antofagasta's public drinking water supply rose substantially in 1958 with the
      introduction of a new water source, and remained elevated until 1970. We used a
      retrospective study design to examine time and location patterns in infant
      mortality between 1950 and 1996, using univariate statistics, graphical
      techniques, and Poisson regression analysis. Results of the study document the
      general declines in late fetal and infant mortality over the study period in both
      locations. The data also indicate an elevation of the late fetal, neonatal, and
      postneonatal mortality rates for Antofagasta, relative to Valparaiso, for
      specific time periods, which generally coincide with the period of highest
      arsenic concentration in the drinking water of Antofagasta. Poisson regression
      analysis yielded an elevated and significant association between arsenic exposure
      and late fetal mortality [rate ratio (RR) = 1.7; 95% confidence interval (CI),
      1.5-1.9], neonatal mortality (RR = 1.53; CI, 1.4-1.7), and postneonatal mortality
      (RR = 1.26; CI, 1.2-1.3) after adjustment for location and calendar time. The
      findings from this investigation may support a role for arsenic exposure in
      increasing the risk of late fetal and infant mortality.

PMID- 10903624
TI  - Parting thoughts
AB  - It has been said that there is no stronger urge than the urge to edit someone
      else's writing. Upon my retirement from the National Institute of Environmental
      Health Sciences (NIEHS), and concurrently from my position as co-editor-in-chief
      of Environmental Health Perspectives, I find that perhaps the stronger urge is
      not to edit but rather to editorialize. Therefore, I would like to provide some
      parting thoughts, and with them hopefully some insights gained from my
      experiences, which have spanned the broad spectrum of environmental health, from
      basic science to public health policy to science communication. I am grateful to
      have had the opportunity to work on many different aspects of the environmental
      health continuum during my time at the NIEHS. In looking back on a career of 30
      years in environmental health, including 28 years as co-editor-in-chief of this
      journal, I am struck by a kaleidoscope of thoughts, emotions, and nostalgia, and
      in juxtaposition to these remembrances, a new perspective on the future. As the
      field of environmental health continues to expand as both a scientific discipline
      and a global movement, I feel that there are some major components which it must
      enthusiastically encompass if the field is to continue to provide real answers to
      the most pressing environmental health issues of our day.

PMID- 10903623
TI  - Blue babies and nitrate-contaminated well water.
AB  - The use of nitrate-contaminated drinking water to prepare infant formula is a
      well-known risk factor for infant methemoglobinemia. Affected infants develop a
      peculiar blue-gray skin color and may become irritable or lethargic, depending on
      the severity of their condition. The condition can progress rapidly to cause coma
      and death if it is not recognized and treated appropriately. Two cases of blue
      baby syndrome were recently investigated. Both cases involved infants who became
      ill after being fed formula that was reconstituted with water from private wells.
      Water samples collected from these wells during the infants' illnesses contained
      nitrate-nitrogen concentrations of 22.9 and 27.4 mg/L.

PMID- 10903625
TI  - Bordering on environmental disaster.
AB  - Millions of people live on the U.S.-Mexico border, drawn by employment
      opportunities from industry and agriculture, and booming growth is expected to
      continue in the coming decades. But the influx of people has long outstripped the
      capacity of border towns and cities to provide for their citizens, and a large
      percentage of the population lives in sprawling, underserviced shantytowns.
      Although investment in environmental infrastructure on both sides has led to
      improvements, shortages among necessities such as drinking water, wastewater
      treatment, and solid waste disposal are at crisis levels. In addition, a host of
      diseases including gastrointestinal infections, asthma, tuberculosis, multiple
      myeloma, systemic lupus erythematosus, hepatitis A, neural tube defects, and lead
      poisoning have been linked to environmental conditions on the border. Ongoing
      binational studies are attempting to define the breadth of the public and
      environmental health crisis and find ways to help make the border a healthier
      place.

PMID- 10903626
TI  - Trusting in a better future: the global environment facility.
AB  - Individual countries acting alone cannot solve environmental problems that span
      national borders. The Global Environment Facility (GEF) was created in 1991 to
      serve as a mechanism for international cooperation in the funding of grants to
      address concerns in four areas of the global environment: biological diversity,
      climate change, international waters, and ozone layer depletion. To date, more
      than 500 projects have been funded with over $2 billion of GEF funds and another
      $5 billion leveraged from public and private sources, including $2 billion in
      matching funds from developing countries.

PMID- 10903627
TI  - Lipid lather removes metals.
AB  - Metal contamination has been linked to birth defects, cancer, skin lesions,
      retardation, learning disabilities, liver and kidney damage, and a host of other
      maladies, and the United States alone will spend some $7 trillion over the next
      five years or so to clean up sites contaminated with metals. Until recently,
      there have only been a few time-consuming, costly methods for dealing with metal
      contamination in soils, but research developed at the University of Arizona uses
      biosurfactants, lipids that form emulsions between liquids of different
      polarities, to virtually "wash" metals out of contaminated soil. Lab tests show
      that 80-100% of single metals including cadmium and lead can be removed through
      the use of environmentally benign biosurfactants.

PMID- 10903628
TI  - A prospective, multicenter study of the epidemiology, management, and outcome of
      severe acute renal failure in a "closed" ICU system.
AB  - The safety and effectiveness of "closed" intensive care units (ICUs) are highly
      controversial. The epidemiology and outcome of acute renal failure (ARF)
      requiring replacement therapy (severe ARF) within a "closed" ICU system are
      unknown. Accordingly, we performed a prospective 3-mo multicenter observational
      study of all Nephrology Units and ICUs in the State of Victoria (all "closed"
      ICUs), Australia, and focused on the epidemiology, treatment, and outcome of
      patients with severe ARF. We collected demographic, clinical, and outcome data
      using standardized case report forms. Nineteen ward patients and 116 adult ICU
      patients had severe ARF (13.4 cases/100, 000 adults/yr). Among the ICU patients
      with severe ARF, 37 had impaired baseline renal function, 91 needed ventilation,
      and 95 needed vasoactive drugs. Intensivists controlled patient care in all
      cases. Continuous renal replacement therapy (CRRT) was used in 111 of the ICU
      patients. Nephrological opinion was sought in only 30 cases. Predicted mortality
      was 59.6%. Actual mortality was 49.2%. Only 11 ICU survivors were dialysis
      dependent at hospital discharge. In the state of Victoria, Australia,
      intensivists manage severe ARF within a "closed" ICU system. Renal replacement is
      typically continuous and outcomes compare favorably with those predicted by
      illness severity scores. Our findings support the safety and efficacy of a
      "closed" ICU model of care.

PMID- 10903629
TI  - Heart disease and the inflammatory response.

PMID- 10903630
TI  - Can heart failure be diagnosed in primary care?

PMID- 10903631
TI  - Third generation oral contraceptives.

PMID- 10903632
TI  - Measuring the performance of health systems.

PMID- 10903633
TI  - Revel in electronic and paper media.

PMID- 10903634
TI  - US court awards $145 pound sterling bn damages against tobacco giants.

PMID- 10903635
TI  - Mandela restores morale of AIDS conference.

PMID- 10903637
TI  - Gordon brown announces pound43bn more for public services

PMID- 10903636
TI  - Donors reject screening panel for malaria projects.

PMID- 10903638
TI  - In brief

PMID- 10903639
TI  - US halts University of Oklahoma clinical research.

PMID- 10903640
TI  - Lung cancer trial has problems in recruitment

PMID- 10903641
TI  - New technique helps to assess vegetative state.

PMID- 10903642
TI  - Interleukin 2 increases CD4 T cell counts in people with HIV

PMID- 10903643
TI  - FDA says statin cannot be sold over the counter.

PMID- 10903644
TI  - Abortion doctor suffers second attack in six years.

PMID- 10903645
TI  - NICE issues guidance for heartburn and indigestion.

PMID- 10903646
TI  - Ireland's measles outbreak kills two

PMID- 10903647
TI  - Exercising his passion.

PMID- 10903650
TI  - The danger of a high C

PMID- 10903648
TI  - Low grade inflammation and coronary heart disease: prospective study and updated
      meta-analyses.
AB  - OBJECTIVE: To assess associations between baseline values of four different
      circulating markers of inflammation and future risk of coronary heart disease,
      potential triggers of systemic inflammation (such as persistent infection), and
      other markers of inflammation. DESIGN: Nested case-control comparisons in a
      prospective, population based cohort. SETTING: General practices in 18 towns in
      Britain. PARTICIPANTS: 506 men who died from coronary heart disease or had a non
      fatal myocardial infarction and 1025 men who remained free of such disease until
      1996 selected from 5661 men aged 40-59 years who provided blood samples in 1978
      1980. MAIN OUTCOME MEASURES: Plasma concentrations of C reactive protein, serum
      amyloid A protein, and serum albumin and leucocyte count. Information on fatal
      and non-fatal coronary heart disease was obtained from medical records and death
      certificates. RESULTS: Compared with men in the bottom third of baseline
      measurements of C reactive protein, men in the top third had an odds ratio for
      coronary heart disease of 2.13 (95% confidence interval 1.38 to 3.28) after age,
      town, smoking, vascular risk factors, and indicators of socioeconomic status were
      adjusted for. Similar adjusted odds ratios were 1.65 (1.07 to 2.55) for serum
      amyloid A protein; 1.12 (0.71 to 1.77) for leucocyte count; and 0.67 (0.43 to
      1.04) for albumin. No strong associations were observed of these factors with
      Helicobacter pylori seropositivity, Chlamydia pneumoniae IgG titres, or plasma
      total homocysteine concentrations. Baseline values of the acute phase reactants
      were significantly associated with one another (P<0.0001), although the
      association between low serum albumin concentration and leucocyte count was
      weaker (P=0.08). CONCLUSION: In the context of results from other relevant
      studies these findings suggest that some inflammatory processes, unrelated to the
      chronic infections studied here, are likely to be involved in coronary heart
      disease.

PMID- 10903651
TI  - I know him

PMID- 10903652
TI  - Lord moran on old age

PMID- 10903649
TI  - Chlamydia pneumoniae infection and mortality from ischaemic heart disease: large
      prospective study.
AB  - OBJECTIVE: To determine whether there is an independent association between
      infection with Chlamydia pneumoniae and ischaemic heart disease. DESIGN:
      Prospective study using a nested case-control design. SETTING: Medical centre in
      London run by BUPA, a private medical organisation. PARTICIPANTS: 21 520
      professional men aged 35-64 who attended for a medical examination in London
      between 1975 and 1982. MAIN OUTCOME MEASURE: Death from ischaemic heart disease.
      RESULTS: The distributions of concentrations of IgG and IgA antibodies to C
      pneumoniae were similar in the 647 men who subsequently died of ischaemic heart
      disease and in 1294 age matched controls who did not. There was no material
      association with heart disease irrespective of the cut-off point chosen to define
      seropositivity. At a cut-off point that defines 15% of controls as positive, for
      example, the odds ratios were 1.26 (95% confidence interval 0.95 to 1.68) for IgG
      and 1.09 (0.82 to 1.43) for IgA. CONCLUSIONS: No material association was found
      between infection with C pneumoniae and ischaemic heart disease. The size and
      prospective design of the study and the socioeconomic homogeneity of the cohort
      minimise both random and systematic error.

PMID- 10903653
TI  - Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and
      meta-analysis.
AB  - OBJECTIVE: To examine the association between coronary heart disease and serum
      markers of chronic Chlamydia pneumoniae infection. DESIGN: "Nested" case-control
      analysis in a prospective cohort study and an updated meta-analysis of previous
      relevant studies. SETTING: General practices in 18 towns in Britain.
      PARTICIPANTS: Of the 5661 men aged 40-59 who provided blood samples during 1978
      80, 496 men who died from coronary heart disease or had non-fatal myocardial
      infarction and 989 men who had not developed coronary heart disease by 1996 were
      included. MAIN OUTCOME MEASURES: IgG serum antibodies to C pneumoniae in baseline
      samples; details of fatal and non-fatal coronary heart disease from medical
      records and death certificates. RESULTS: 200 (40%) of the 496 men with coronary
      heart disease were in the top third of C pneumoniae titres compared with 329
      (33%) of the 989 controls. The corresponding odds ratio for coronary heart
      disease was 1.66 (95% confidence interval 1.25 to 2.21), which fell to 1.22 (0.82
      to 1.82) after adjustment for smoking and indicators of socioeconomic status. No
      strong associations were observed between C pneumoniae IgG titres and blood lipid
      concentrations, blood pressure, or plasma homocysteine concentration. In
      aggregate, the present study and 14 other prospective studies of C pneumoniae IgG
      titres included 3169 cases, yielding a combined odds ratio of 1. 15 (0.97 to
      1.36), with no significant heterogeneity among the separate studies (chi(2)=10.5,
      df=14; P>0.1). CONCLUSION: This study, together with a meta-analysis of previous
      prospective studies, reliably excludes the existence of any strong association
      between C pneumoniae IgG titres and incident coronary heart disease. Further
      studies are required, however, to confirm or refute any modest association that
      may exist, particularly at younger ages.

PMID- 10903654
TI  - Effect of improved data collection on breast cancer incidence and survival:
      reconciliation of a registry with a clinical database.

PMID- 10903656
TI  - Science commentary: echocardiography.

PMID- 10903657
TI  - Not such an angel?

PMID- 10903655
TI  - Do patients with suspected heart failure and preserved left ventricular systolic
      function suffer from "diastolic heart failure" or from misdiagnosis? A
      prospective descriptive study.
AB  - OBJECTIVES: To characterise the clinical features of patients with suspected
      heart failure but preserved left ventricular systolic function to determine if
      they have other potential causes for their symptoms rather than being diagnosed
      with "diastolic heart failure." DESIGN: Prospective descriptive study. SETTING:
      Outpatient based direct access echocardiography service. PARTICIPANTS: 159
      consecutive patients with suspected heart failure referred by general
      practitioners. MAIN OUTCOME MEASURES: Symptoms (including shortness of breath,
      ankle oedema, and paroxysmal nocturnal dyspnoea) and history of coronary heart
      disease and chronic pulmonary disease. Transthoracic echocardiography, body mass
      index, pulmonary function tests, and electrocardiography. RESULTS: 109 of 159
      participants had suspected heart failure in the absence of left ventricular
      systolic dysfunction, valvular heart disease, or atrial fibrillation. Of these
      109, 40 were either obese or very obese, 54 had a reduction in forced expiratory
      volume in 1 second to </=70%, and 97 had a peak expiratory flow rate </=70% of
      normal. Thirty one patients had a history of angina, 12 had had a myocardial
      infarction, and seven had undergone a coronary artery bypass graft. Only seven
      patients lacked a recognised explanation for their symptoms. CONCLUSIONS: For
      most patients with a diagnosis of heart failure but preserved left ventricular
      systolic function there is an alternative explanation for their symptoms-for
      example, obesity, lung disease, and myocardial ischaemia-and the diagnosis of
      diastolic heart failure is rarely needed. These alternative diagnoses should be
      rigorously sought and managed accordingly.

PMID- 10903658
TI  - Management of acute coronary syndromes.

PMID- 10903659
TI  - Rare presentation of maternal primary hyperparathyroidism.

PMID- 10903660
TI  - ABC of oral health. Swellings and red, white, and pigmented lesions.

PMID- 10903661
TI  - Who is speaking for children and adolescents and for their health at the policy
      level?

PMID- 10903662
TI  - War and mental health: a brief overview.

PMID- 10903663
TI  - What medicine's all about

PMID- 10903664
TI  - Obituaries

PMID- 10903665
TI  - BMA supports medical majority on GMC

PMID- 10903666
TI  - Practising evidence based geriatrics

PMID- 10903667
TI  - Matters of life and death

PMID- 10903668
TI  - Raising awareness or spreading fear?

PMID- 10903670
TI  - NHS performance indicators

PMID- 10903669
TI  - Reporting NHS performance: how did the media perform?

PMID- 10903672
TI  - Power to the paperwork

PMID- 10903671
TI  - The forgotten children

PMID- 10903673
TI  - Hearts and minds and meta-analyses

PMID- 10903674
TI  - Inflammatory processes may be at work in heart disease

PMID- 10903675
TI  - C pneumoniae infection is not strongly associated with heart disease

PMID- 10903676
TI  - Better ascertainment of cancer cases may lead to reduced survival

PMID- 10903678
TI  - Children's health is neglected in England's national policy

PMID- 10903677
TI  - Diastolic heart failure is an overused diagnosis

PMID- 10903679
TI  - Communities are the main source of resilience in the face of conflict

PMID- 10903680
TI  - Prehospital medical care

PMID- 10903681
TI  - Editor's page : new education and publication initiatives in july 2000

PMID- 10903682
TI  - New enhancements for RadioGraphics online: supplemental material and CME.

PMID- 10903683
TI  - Midface anomalies in children.
AB  - A variety of congenital midface anomalies occur in children. High-resolution
      computed tomography (CT) and magnetic resonance (MR) imaging have proved helpful
      in determining the nature and extent of dysplasia, thereby facilitating treatment
      planning. A classification system has been developed that groups these anomalies
      into four categories based on embryogenesis and anatomic location. These
      categories comprise anomalies that are related to the nasal cavity, nasofrontal
      region, nasolacrimal apparatus, and craniofacial syndromes. CT is the imaging
      modality of choice in children with possible choanal atresia, pyriform aperture
      stenosis, or anomalies of the nasolacrimal duct (eg, nasolacrimal duct stenosis,
      dacryocystoceles). MR imaging is the modality of choice in patients with
      congenital midface masses (eg, dermoid and epidermoid cysts, nasal gliomas,
      encephaloceles) and craniofacial syndromes (eg, Apert syndrome, Crouzon syndrome,
      Treacher Collins syndrome). In many cases, however, both CT and MR imaging are
      required to adequately evaluate midface anomalies. Familiarity with the
      characteristic imaging features of these anomalies along with knowledge of
      midface embryogenesis and normal developmental anatomy is essential to prevent
      misinterpretation of anatomic variations that may simulate disease.

PMID- 10903684
TI  - US of the spinal cord in newborns: spectrum of normal findings, variants,
      congenital anomalies, and acquired diseases.
AB  - Ultrasonography (US) of the spinal cord is performed in newborns with signs of
      spinal disease (cutaneous lesions of the back, deformities of the spinal column,
      neurologic disturbances, suspected spinal cord injury due to traumatic birth, and
      syndromes with associated spinal cord compression). The examination is performed
      with high-frequency linear- and curved-array transducers in the sagittal and
      axial planes from the craniocervical junction to the sacrum. Normal variants such
      as transient dilatation of the central canal and ventriculus terminalis can be
      demonstrated with US. US allows detection of congenital malformations, such as
      myelocele or myelomeningocele, spinal lipoma, dorsal dermal sinus, tight filum
      terminale syndrome, diastematomyelia, terminal myelocystocele, lateral
      meningocele, caudal regression syndrome, and hydromyelia or syringomyelia.
      Acquired intraspinal diseases following birth trauma and transient alterations
      after lumbar puncture can also be detected with US. US can demonstrate the entire
      spectrum of intraspinal anatomy and pathologic conditions with high geometric
      resolution. Therefore, US should be considered the initial imaging modality of
      choice for investigating the spinal cord in newborns.

PMID- 10903685
TI  - MR cholangiopancreatography of bile and pancreatic duct abnormalities with
      emphasis on the single-shot fast spin-echo technique.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is used for noninvasive work
      up of patients with pancreaticobiliary disease. MRCP is comparable with invasive
      endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis of
      extrahepatic bile duct abnormalities. In patients with choledocholithiasis,
      calculi appear as dark filling defects within the high-signal-intensity fluid at
      MRCP. Benign strictures due to sclerosing cholangitis are multifocal and
      alternate with slight dilatation or normal-caliber bile ducts, producing a beaded
      appearance. Dilatation of both the pancreatic and bile ducts at MRCP is highly
      suggestive of a pancreatic head malignancy. Side-branch ectasia is the most
      prominent and specific feature of chronic pancreatitis. MRCP is more sensitive
      than ERCP in detection of pancreatic pseudocysts because less than 50% of
      pseudocysts fill with contrast material. Because the mucin secreted by biliary
      cystadenomas and cystadenocarcinomas causes filling defects and partial
      obstruction of contrast material at ERCP, MRCP is potentially more accurate in
      demonstrating the extent of these tumors. In patients with biliary-enteric
      anastomoses, MRCP is the imaging modality of choice for the work-up of suspected
      pancreaticobiliary disease. A potential use of MRCP is the demonstration of
      aberrant bile duct anatomy before cholecystectomy. MRCP is also accurate in
      detection of pancreas divisum.

PMID- 10903687
TI  - Practice corner- : morale in healthcare: why not go over the side?

PMID- 10903686
TI  - Radiologic manifestations of sclerosing cholangitis with emphasis on MR
      cholangiopancreatography.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is a relatively new,
      noninvasive cholangiographic technique that is comparable with invasive
      endoscopic retrograde cholangiopancreatography (ERCP) in the detection and
      characterization of extrahepatic bile duct abnormalities. The role of MRCP in
      evaluation of the intrahepatic bile ducts, especially in patients with primary or
      secondary sclerosing cholangitis, is under investigation. The key
      cholangiographic features of primary sclerosing cholangitis are randomly
      distributed annular strictures out of proportion to upstream dilatation. As the
      fibrosing process worsens, strictures increase and the ducts become obliterated,
      and the peripheral ducts cannot be visualized to the periphery of the liver at
      ERCP. In addition, the acute angles formed with the central ducts become more
      obtuse. With further progression, strictures of the central ducts prevent
      peripheral ductal opacification at ERCP. Cholangiocarcinoma occurs in 10%-15% of
      patients with primary sclerosing cholangitis; cholangiographic features that
      suggest cholangiocarcinoma include irregular high-grade ductal narrowing with
      shouldered margins, rapid progression of strictures, marked ductal dilatation
      proximal to strictures, and polypoid lesions. Secondary sclerosing and
      nonsclerosing processes can mimic primary sclerosing cholangitis at
      cholangiography. These processes include ascending cholangitis, oriental
      cholangiohepatitis, acquired immunodeficiency syndrome-related cholangitis,
      chemotherapy-induced cholangitis, ischemic cholangitis after liver
      transplantation, eosinophilic cholangitis, and metastases.

PMID- 10903688
TI  - Aortic prosthetic graft infections: radiologic manifestations and implications
      for management.
AB  - Prosthetic graft infections are an uncommon complication of aortic bypass. These
      infections may have serious sequelae such as limb loss and can be lethal. They
      are hard to eradicate and, under certain circumstances, difficult to diagnose.
      Usually, computed tomography (CT) is the most efficacious imaging method for
      diagnosis of graft infections due to its quick availability. The sensitivity of
      magnetic resonance imaging in detection of perigraft infection has not been
      thoroughly investigated but is probably similar to that of CT. After the early
      postoperative period, persistent or expanding perigraft soft tissue, fluid, and
      gas are the CT findings of graft infection. Aortoenteric fistula should be
      considered a subset of aortic graft infection; however, perigraft air is more
      likely to be seen with an aortoenteric fistula. Other conditions associated with
      graft infection include pseudoaneurysm, hydronephrosis, and osteomyelitis.
      Adjunctive studies such as sinography, ultrasonography, gallium scanning, and
      labeled white blood cell scanning can be quite useful in diagnosis, determination
      of the extent of disease, and selection of the treatment modality. White blood
      cell scanning is an important complementary test to CT in ambiguous cases, such
      as in the early postoperative period, and may be more sensitive in detection of
      early graft infection.

PMID- 10903690
TI  - Myxoid liposarcoma: appearance at MR imaging with histologic correlation.
AB  - Although myxoid liposarcoma is a subtype of liposarcoma, it may be difficult to
      establish the correct diagnosis with magnetic resonance (MR) imaging due to the
      lack of fat signal intensity. Without the administration of gadolinium contrast
      material, the tumor may even mimic a cystic tumor. A spectrum of MR imaging
      abnormalities occur in myxoid liposarcoma, depending on the amount of fat and
      myxoid material, the degree of cellularity and vascularity, and the presence of
      necrosis. Most myxoid liposarcomas have lacy or linear, amorphous foci of fat.
      Some myxoid liposarcomas appear to be cystic at nonenhanced MR imaging, although
      they enhance like other solid masses at contrast material-enhanced MR imaging.
      The enhancing areas within the tumor represent increased cellularity and
      vascularity; the nonenhancing areas represent necrosis, reduced cellularity, and
      accumulated mucinous material. Gadolinium-enhanced imaging is important in
      differentiating myxoid liposarcoma from benign cystic tumors. Characterization of
      the tumor with MR imaging plays an important role in the management of myxoid
      liposarcoma.

PMID- 10903689
TI  - Penetrating atherosclerotic ulcer of the aorta: imaging features and disease
      concept.
AB  - Penetrating atherosclerotic ulcer is an ulcerating atherosclerotic lesion that
      penetrates the elastic lamina and is associated with hematoma formation within
      the media of the aortic wall. This pathologic condition is distinct from classic
      aortic dissection and aortic rupture; however, care should be taken in making the
      diagnosis, particularly if the disease is discovered incidentally. At computed
      tomography (CT), penetrating atherosclerotic ulcer manifests as focal involvement
      with adjacent subintimal hematoma and is often associated with aortic wall
      thickening or enhancement. Magnetic resonance imaging is superior to conventional
      CT in differentiating acute intramural hematoma from atherosclerotic plaque and
      chronic intraluminal thrombus and allows unenhanced multiplanar imaging. Spiral
      CT involves shorter examination times and allows high-quality two- and three
      dimensional image reconstruction. CT angiography can demonstrate complex spatial
      relationships, mural abnormalities, and extraluminal pathologic conditions.
      Transesophageal echocardiography has been reported to be highly sensitive and
      specific in the differentiation of aortic disease, and intravascular
      ultrasonography may also be useful in this setting. Although rupture or other
      life-threatening complications are rare, patients with penetrating
      atherosclerotic ulcer must be followed up, particularly during the 1st month
      after onset. Surgical treatment may become necessary in cases involving evidence
      of intramural hematoma expansion, signs of impending rupture, inability to
      control pain, or blood pressure changes.

PMID- 10903691
TI  - Scenes from the past: Nikola Tesla's legacy to modern imaging.

PMID- 10903692
TI  - MR imaging of nontraumatic brachial plexopathies: frequency and spectrum of
      findings.
AB  - Magnetic resonance imaging is the method of choice for evaluating patients with a
      nontraumatic brachial plexopathy. Although there is a wide range of disease
      processes that may cause a brachial plexopathy, radiation fibrosis, primary and
      metastatic lung cancer, and metastatic breast cancer account for almost three
      fourths of the causes. Radiation fibrosis, the most common cause in our series,
      may occur several months to years after the completion of therapy. Findings of
      radiation fibrosis include (a) thickening and diffuse enhancement of the brachial
      plexus without a focal mass and (b) soft-tissue changes with low signal intensity
      on both T1- and T2-weighted images. Lung cancer arising in the lung apex may
      invade the lower portion of the brachial plexus. Many tumors may metastasize to
      the brachial plexus, causing a brachial plexopathy. Breast cancer is the most
      likely to metastasize because major lymphatic drainage routes for the breast
      course through the apex of the axilla.

PMID- 10903693
TI  - Choice of phantom material and test protocols to determine radiation exposure
      rates for fluoroscopy.
AB  - The image intensifier entrance exposure rate (IIEER)) and entrance skin exposure
      rate (ESER) are two characteristics that can be used to determine whether a
      fluoroscope is adjusted to operate at an optimal dose rate level. This article
      presents solutions to some of the practical problems that are encountered when
      measuring these parameters. Because the energy response of the ion chamber used
      to measure exposure rates is different from that of the image intensifier, a
      fluoroscope with a perfect automatic exposure rate control will have an IIEER
      that depends on the phantom composition, phantom thickness, and x-ray tube
      potential. The authors developed a simple mathematic model to investigate the
      relationship of ion chamber response to image intensifier response and to
      determine the effects of phantom composition and thickness. Results from this
      model were compared with measurements made with two C-arm fluoroscopes.
      Variations of 40% or more in the IIEER and ESER can be ascribed to these
      phenomena.

PMID- 10903694
TI  - Pneumomediastinum revisited.
AB  - Pneumomediastinum may result from a variety of causes that may be either
      intrathoracic (eg, narrowed or plugged airway, straining against a closed
      glottis, blunt chest trauma, alveolar rupture) or extrathoracic (eg, sinus
      fracture, iatrogenic manipulation in dental extraction, perforation of a hollow
      viscus [corrected]. The radiographic signs of pneumomediastinum depend on the
      depiction of normal anatomic structures that are outlined by the air as it leaves
      the mediastinum. These signs include the thymic sail sign, "ring around the
      artery" sign, tubular artery sign, double bronchial wall sign, continuous
      diaphragm sign, and extrapleural sign. In distal esophageal rupture, air may
      migrate from the mediastinum into the pulmonary ligament. Pneumomediastinum may
      be difficult to differentiate from medial pneumothorax and pneumopericardium.
      Occasionally, normal anatomic structures (eg, major fissure, anterior junction
      line) may simulate air within the mediastinum. Iatrogenic entities that may
      simulate pneumomediastinum include helium in the balloon of an intraaortic assist
      device. In addition, pneumomediastinum may be simulated by the Mach band effect,
      which manifests as a region of lucency adjacent to structures with convex
      borders. The absence of an opaque line, which is typically seen in
      pneumomediastinum, can aid in differentiation. Computed tomographic (CT) digital
      radiography and conventional CT can also be helpful in establishing or confirming
      the diagnosis.

PMID- 10903695
TI  - How to create an effective scientific exhibit: analysis of award-winning exhibits
      from the 1998 RSNA meeting.
AB  - Although the most important component of an effective scientific exhibit is
      content, the way in which an exhibit is constructed can greatly influence its
      overall effectiveness. Choice of format should be determined by carefully
      analyzing the purpose of one's exhibit, expected audience, and data at hand, as
      well as type of meeting and funding. Depending on the type of data to be
      presented and available equipment and budget, the most appropriate style for a
      scientific exhibit may be a traditional mat board, computer-generated tiles or
      large-print backboard panel, traditional mat board with viewbox exhibit, matted
      transparency tiles with viewbox exhibit, or computer-generated large-film
      display. The authors analyzed 993 of 1, 041 (95.4%) scientific exhibits on
      display at the 84th RSNA Scientific Assembly and Annual Meeting and categorized
      each exhibit according to the following characteristics: display type and size,
      color scheme, display font size, and graphic styles. These characteristics were
      then correlated with scientific exhibit and design awards as well as invitations
      for submission to RadioGraphics. Chance of winning an award or being asked to
      publish the presentation in RadioGraphics was significantly increased for viewbox
      exhibits (compared with backboard panel exhibits) and for larger exhibits
      (compared with smaller exhibits).

PMID- 10903696
TI  - Invited commentary

PMID- 10903698
TI  - Illuminations

PMID- 10903697
TI  - Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation.
AB  - Primary cardiac and pericardial neoplasms are rare lesions and include both
      benign and malignant histologic types. Myxoma is the most frequent primary
      cardiac neoplasm, but other benign tumors include papillary fibroelastoma,
      rhabdomyoma, fibroma, hemangioma, lipoma, and paraganglioma. Cardiac sarcoma
      represents the second most common primary cardiac neoplasm. Lymphoma can also
      affect the heart primarily. Pericardial tumors that affect the heart include
      benign teratomas and malignant mesotheliomas. Patients affected with cardiac or
      pericardial neoplasms often present with cardiovascular compromise or embolic
      phenomena and exhibit cardiomegaly at chest radiography. Benign cardiac tumors
      typically manifest as intracavitary, mural, or epicardial focal masses, whereas
      malignant tumors demonstrate invasive features and may involve the heart
      diffusely. Benign lesions can usually be successfully excised, but patients with
      malignant lesions have an extremely poor prognosis.

PMID- 10903699
TI  - Techniques of dynamic subtraction contrast-enhanced MR angiography.

PMID- 10903700
TI  - The AAPM/RSNA physics tutorial for residents: general overview of fluoroscopic
      imaging.
AB  - Fluoroscopy is used to visualize the motion of internal fluids, structures, and
      devices. During a fluoroscopic examination, the operator controls activation of
      the x-ray tube for real-time imaging of the patient. The article provides a
      general overview of fluoroscopic imaging from its initial development to modern
      use. Early fluoroscopes produced a dim image on a fluorescent screen that
      required dark adaptation of the physician's eyes to optimize viewing conditions.
      Image intensifiers were later developed to replace the fluorescent screen and
      increase image brightness. Modern fluoroscopy systems include an image
      intensifier with television image display and a choice of several different types
      of image recording devices. Fluoroscopic equipment is available in many different
      configurations for use in a wide variety of clinical applications.

PMID- 10903701
TI  - Comparison of tissue harmonic imaging with conventional US in abdominal disease.
AB  - Harmonic waves are generated from nonlinear distortion of an acoustic signal as
      an ultrasound wave insonates tissues in the body. These beams are integer
      multiples of a fundamental transmitted frequency. Potential advantages of
      harmonic imaging include improved axial resolution due to higher frequencies and
      better lateral resolution due to narrower beams. Decreased noise from side lobes
      improves signal-to-noise ratios and reduces artifacts. Deleterious effects of the
      body wall are also reduced. The authors prospectively studied ultrasonographic
      (US) findings in 100 adult patients with 202 abdominal lesions by comparing
      harmonic US images with conventional US images. The results were subjected to
      statistical analysis. Harmonic imaging was superior to conventional US in regard
      to lesion visibility and diagnostic confidence. Harmonic imaging was particularly
      useful for depicting cystic lesions and those containing echogenic tissues such
      as fat, calcium, or air. In patients with a body mass index of 30 or more,
      harmonic imaging was clearly better for lesion visibility and confidence of
      diagnosis. The authors recommend routine use of harmonic imaging for abdominal US
      studies in all adult patients.

PMID- 10903702
TI  - Teleradiology as a foundation for an enterprise-wide health care delivery system.
AB  - An effective, integrated telemedicine system has been developed that allows (a)
      teleconsultation between local primary health care providers (primary care
      physicians and general radiologists) and remote imaging subspecialists and (b)
      active patient participation related to his or her medical condition and patient
      education. The initial stage of system development was a traditional
      teleradiology consultation service between general radiologists and specialists;
      this established system was expanded to include primary care physicians and
      patients. The system was developed by using a well-defined process model,
      resulting in three integrated modules: a patient module, a primary health care
      provider module, and a specialist module. A middle agent layer enables tailoring
      and customization of the modules for each specific user type. Implementation by
      using Java and the Common Object Request Broker Architecture standard facilitates
      platform independence and interoperability. The system supports (a)
      teleconsultation between a local primary health care provider and an imaging
      subspecialist regardless of geographic location and (b) patient education and
      online scheduling. The developed system can potentially form a foundation for an
      enterprise-wide health care delivery system. In such a system, the role of
      radiologist specialists is enhanced from that of a diagnostician to the
      management of a patient's process of care.

PMID- 10903703
TI  - 1999 plenary session: Friday imaging symposium: algorithmic controversies.

PMID- 10903704
TI  - Radionuclide imaging in the evaluation of acute gastrointestinal bleeding.

PMID- 10903705
TI  - Angiographic localization and transcatheter treatment of gastrointestinal
      bleeding.

PMID- 10903706
TI  - Improvement in detection of pulmonary nodules: digital image processing and
      computer-aided diagnosis.

PMID- 10903707
TI  - Functional CT: lung nodule evaluation.

PMID- 10903708
TI  - 1999 plenary session: Friday imaging symposium : evaluation of focal pulmonary
      abnormalities with FDG PET.

PMID- 10903709
TI  - 1999 plenary session: Friday imaging symposium: role of small-peptide
      radiopharmaceuticals in the evaluation of deep venous thrombosis.

PMID- 10903711
TI  - 1999 plenary session: Friday imaging symposium : CT diagnosis of pulmonary
      embolism and deep venous thrombosis.

PMID- 10903710
TI  - 1999 plenary session: Friday imaging symposium : venous US of lower-extremity
      deep venous thrombosis: when is US insufficient?

PMID- 10903712
TI  - New criteria for ventilation-perfusion lung scan interpretation: a basis for
      optimal interaction with helical CT angiography.

PMID- 10903713
TI  - Cutting edge: cell autonomous rather than environmental factors control bacterial
      superantigen-induced T cell anergy in vivo.
AB  - Anergic T cells display a marked decrease in their ability to produce IL-2 and to
      proliferate in the presence of an appropriate antigenic signal. Two nonmutually
      exclusive classes of models have been proposed to explain the persistence of T
      cell anergy in vivo. While some reports indicate that anergic T cells have
      intrinsic defects in signaling pathways or transcriptional activities, other
      studies suggest that anergy is maintained by environmental "suppressor" factors
      such as cytokines or Abs. To distinguish between these conflicting hypotheses, we
      employed the well-characterized bacterial superantigen model system to evaluate
      in vivo the ability of a trace population of adoptively transferred naive or
      anergized T cells to proliferate in a naive vs anergic environment upon
      subsequent challenge. Our data clearly demonstrate that bacterial superantigen
      induced T cell anergy is cell autonomous and independent of environmental
      factors.

PMID- 10903714
TI  - Anergic T cells inhibit the antigen-presenting function of dendritic cells.
AB  - The phenomena of infectious tolerance and linked-suppression are well
      established, but the mechanisms involved are incompletely defined. Anergic T
      cells can inhibit responsive T cells in vitro and prolong skin allograft survival
      in vivo. In this study the mechanisms underlying these events were explored.
      Allospecific mouse T cell clones rendered unresponsive in vitro inhibited
      proliferation by responsive T cells specific for the same alloantigens. The
      inhibition required the presence of APC, in that the response to coimmobilized
      anti-CD3 and anti-CD28 Abs was not inhibited. Coculture of anergic T cells with
      bone marrow-derived dendritic cells (DC) led to profound inhibition of the
      ability of the DC to stimulate T cells with the same or a different specificity.
      After coculture with anergic T cells expression of MHC class II, CD80 and CD86 by
      DC were down-regulated. These effects did not appear to be due to a soluble
      factor in that inhibition was not seen in Transwell experiments, and was not
      reversed by addition of neutralizing anti-IL-4, anti-IL-10, and anti-TGF-beta
      Abs. Taken together, these data suggest that anergic T cells function as
      suppressor cells by inhibiting Ag presentation by DC via a cell contact-dependent
      mechanism.

PMID- 10903715
TI  - Requirement of mature dendritic cells for efficient activation of influenza A
      specific memory CD8+ T cells.
AB  - It is critical to identify the developmental stage of dendritic cells (DCs) that
      is most efficient at inducing CD8+ T cell responses. Immature DCs can be
      generated from monocytes with GM-CSF and IL-4, while maturation is accomplished
      by the addition of stimuli such as monocyte-conditioned medium, CD40 ligand, and
      LPS. We evaluated the ability of human monocytes and immature and mature DCs to
      induce CD8+ effector responses to influenza virus Ags from resting memory cells.
      We studied replicating virus, nonreplicating virus, and the HLA-A*0201-restricted
      influenza matrix protein peptide. Sensitive and quantitative assays were used to
      measure influenza A-specific immune responses, including MHC class I tetramer
      binding assays, enzyme-linked immunospot assays for IFN-gamma production, and
      generation of cytotoxic T cells. Mature DCs were demonstrated to be superior to
      immature DC in eliciting IFN-gamma production from CD8+ effector cells.
      Furthermore, only mature DCs, not immature DCs, could expand and differentiate
      CTL precursors into cytotoxic effector cells over 7 days. An exception to this
      was immature DCs infected with live influenza virus, because of the virus's known
      maturation effect. Finally, mature DCs pulsed with matrix peptide induced CTLs
      from highly purified CD8+ T cells without requiring CD4+ T cell help. These
      differences between DC stages were independent of Ag concentrations or the number
      of immature DCs. In contrast to DCs, monocytes were markedly inferior or
      completely ineffective stimulators of T cell immunity. Our data with several
      qualitatively different assays of the memory CD8+ T cell response suggest that
      mature cells should be considered as immunotherapeutic adjuvants for Ag delivery.

PMID- 10903716
TI  - Lineage-specific telomere shortening and unaltered capacity for telomerase
      expression in human T and B lymphocytes with age.
AB  - Age effects on telomere length and telomerase expression in peripheral blood
      lymphocytes were analyzed from 121 normal individuals age newborn to 94 years and
      revealed several new findings. 1) Telomere shortening was observed in CD4+ and
      CD8+ T and B cells with age. However, the rate of telomere loss was significantly
      different in these populations, 35 +/- 8, 26 +/- 7, and 19 +/- 7 bp/year for CD4+
      and CD8+ T and B cells, respectively. In addition, CD4+ T cells had the longest
      average telomeres at all ages, followed by B cells, with CD8+ T cell telomeres
      the shortest, suggesting that these lymphocyte populations may have different
      replicative histories in vivo. 2) Telomerase activity in freshly isolated T and B
      cells was indistinguishably low to undetectable at all ages but was markedly
      increased after Ag and costimulatory receptors mediated stimulation in vitro.
      Furthermore, age did not alter the magnitude of telomerase activity induced after
      stimulation of T or B lymphocytes through Ag and costimulatory receptors or in
      response to PMA plus ionomycin treatment. 3) The levels of telomerase activity
      induced by in vitro stimulation varied among individual donors but were highly
      correlated with the outcome of telomere length change in CD4+ T cells after Ag
      receptor-mediated activation. Together, these results indicate that rates of age
      associated loss of telomere length in vivo in peripheral blood lymphocytes is
      specific to T and B cell subsets and that age does not significantly alter the
      capacity for telomerase induction in lymphocytes.

PMID- 10903717
TI  - FDF03, a novel inhibitory receptor of the immunoglobulin superfamily, is
      expressed by human dendritic and myeloid cells.
AB  - In this study, we describe human FDF03, a novel member of the Ig superfamily
      expressed as a monomeric 44-kDa transmembrane glycoprotein and containing a
      single extracellular V-set Ig-like domain. Two potential secreted isoforms were
      also identified. The gene encoding FDF03 mapped to chromosome 7q22. FDF03 was
      mostly detected in hemopoietic tissues and was expressed by monocytes,
      macrophages, and granulocytes, but not by lymphocytes (B, T, and NK cells),
      indicating an expression restricted to cells of the myelomonocytic lineage. FDF03
      was also strongly expressed by monocyte-derived dendritic cells (DC) and
      preferentially by CD14+/CD1a- DC derived from CD34+ progenitors. Moreover, flow
      cytometric analysis showed FDF03 expression by CD11c+ blood and tonsil DC, but
      not by CD11c- DC precursors. The FDF03 cytoplasmic tail contained two
      immunoreceptor tyrosine-based inhibitory motif (ITIM)-like sequences. When
      overexpressed in pervanadate-treated U937 cells, FDF03 was tyrosine
      phosphorylated and recruited Src homology-2 (SH2) domain-containing protein
      tyrosine phosphatase (SHP)-2 and to a lesser extent SHP-1. Like engagement of the
      ITIM-bearing receptor LAIR-1/p40, cross-linking of FDF03 inhibited calcium
      mobilization in response to CD32/FcgammaRII aggregation in transfected U937
      cells, thus demonstrating that FDF03 can function as an inhibitory receptor.
      However, in contrast to LAIR-1/p40, cross-linking of FDF03 did not inhibit GM-CSF
      induced monocyte differentiation into DC. Thus, FDF03 is a novel ITIM-bearing
      receptor selectively expressed by cells of myeloid origin, including DC, that may
      regulate functions other than that of the broadly distributed LAIR-1/p40
      molecule.

PMID- 10903718
TI  - Redundant and opposing functions of two tyrosine kinases, Btk and Lyn, in mast
      cell activation.
AB  - Protein-tyrosine kinases play crucial roles in mast cell activation through the
      high-affinity IgE receptor (FcepsilonRI). In this study, we have made the
      following observations on growth properties and FcepsilonRI-mediated signal
      transduction of primary cultured mast cells from Btk-, Lyn-, and Btk/Lyn
      deficient mice. First, Lyn deficiency partially reversed the survival effect of
      Btk deficiency. Second, FcepsilonRI-induced degranulation and leukotriene release
      were almost abrogated in Btk/Lyn doubly deficient mast cells while singly
      deficient cells exhibited normal responses. Tyrosine phosphorylation of cellular
      proteins including phospholipases C-gamma1 and C-gamma2 was reduced in Btk/Lyn
      deficient mast cells. Accordingly, FcepsilonRI-induced elevation of intracellular
      Ca2+ concentrations and activation of protein kinase Cs were blunted in the
      doubly deficient cells. Third, in contrast, Btk and Lyn demonstrated opposing
      roles in cytokine secretion and mitogen-activated protein kinase activation. Lyn
      deficient cells exhibited enhanced secretion of TNF-alpha and IL-2 apparently
      through the prolonged activation of extracellular signal-related kinases and c
      Jun N-terminal kinase. Potentially accounting for this phenomenon and robust
      degranulation in Lyn-deficient cells, the activities of protein kinase Calpha and
      protein kinase CbetaII, low at basal levels, were enhanced in these cells.
      Fourth, cytokine secretion was severely reduced and c-Jun N-terminal kinase
      activation was completely abrogated in Btk/Lyn-deficient mast cells. The data
      together demonstrate that Btk and Lyn are involved in mast cell signaling
      pathways in distinctly different ways, emphasizing that multiple signal outcomes
      must be evaluated to fully understand the functional interactions of individual
      signaling components.

PMID- 10903719
TI  - Transient translocation of the B cell receptor and Src homology 2 domain
      containing inositol phosphatase to lipid rafts: evidence toward a role in calcium
      regulation.
AB  - Membrane microdomains (lipid rafts) are enriched in selected signaling molecules
      and may compartmentalize receptor-mediated signals. Here, we report that in
      primary human B lymphocytes and in Ramos B cells B cell receptor (BCR)
      stimulation induces rapid and transient redistribution of a subset of engaged
      BCRs to lipid rafts and phosphorylation of raft-associated tyrosine kinase
      substrates. Cholesterol sequestration disrupted the lipid rafts, preventing BCR
      redistribution, but did not inhibit tyrosine kinase activation or phosphorylation
      of mitogen-activated protein kinase/extracellular regulated kinase. However, raft
      disruption enhanced the release of calcium from intracellular stores, suggesting
      that rafts may sequester early signaling events that down-regulate calcium flux.
      Consistent with this, BCR stimulation induced rapid and transient translocation
      of the Src homology 2 domain-containing inositol phosphatase, SHIP, into lipid
      rafts.

PMID- 10903720
TI  - CpG-DNA-mediated transient lymphadenopathy is associated with a state of Th1
      predisposition to antigen-driven responses.
AB  - Infections can influence concurrent and subsequent Th1 vs Th2 immune responses to
      Ags. Through pattern recognition of foreign unmethylated CpG dinucleotides, the
      vertebrate innate immune system can sense infectious danger and typically replies
      with a Th1-polarized adaptive immune response. We examined whether CpG-DNA
      exposure would influence subsequent responses to infection and soluble Ags. CpG
      DNA injection led to local lymphadenopathy characterized by maintenance of
      cellular composition with some biasing toward elevated dendritic cell
      composition. Sustained local production of IL-12 and IFN-gamma from dendritic
      cells and T cells was shown. Prior injection by up to 2 wk with CpG-DNA protected
      BALB/c mice from Th2 driven lethal leishmaniasis. CpG-DNA injection by up to 5 wk
      before soluble Ag challenge resulted in the generation of Ag-specific CTL, Th1
      recall responses to Ag, and Th1-polarized Ag-specific Abs. Thus, CpG-DNA
      instigated a local predisposition for intense CTL responses and Th1-polarized
      immune responses to subsequent infections or Ag challenge. The induction by the
      innate immune system of a locally contained hypersensitivity could represent a
      capacitating immune reaction yielding rapid conditioned responses to secondary
      infections.

PMID- 10903721
TI  - Early onset of CD8 transgene expression inhibits the transition from DN3 to DP
      thymocytes.
AB  - In this paper we show that the effects of transgenic coreceptor expression on
      thymocyte development depend on the onset of transgene expression. Thus, a CD8
      transgene expressed on CD44+CD25+ (DN2) and CD44-CD25+ (DN3) cells causes a
      partial block at the stage when TCRbeta selection takes place and diminishes
      expansion at the subsequent developmental stages, resulting in increased DN3 and
      markedly reduced double-positive (DP) thymocyte numbers. This effect is evident
      on a polyclonal TCR repertoire as well as in TCR-transgenic mice (F5). By
      contrast, a CD8 transgene that leads to the same degree of overexpression on DP
      thymocytes, but is not expressed on double-negative subsets, has no effect on
      thymus size or composition. Therefore, the reduction of DP thymocyte numbers in
      CD8 TCRtg mice can be attributed to interferences at early developmental stages
      rather than to increased negative selection of DP cells.

PMID- 10903722
TI  - Age-dependent alterations in the assembly of signal transduction complexes at the
      site of T cell/APC interaction.
AB  - TCR interaction with peptide-MHC complexes triggers migration of protein kinases,
      actin-binding proteins, and other accessory molecules to the T cell/APC synapse.
      We used confocal immunofluorescence methods to show that the adapter protein LAT
      (linker for activation of T cells) and the guanine nucleotide exchange factor Vav
      also move to the APC interface in mouse CD4 T cells conjugated to anti-CD3
      hybridoma cells, and in TCR-transgenic CD4 cells conjugated to APC bearing
      agonist (but not closely related nonagonist) peptides. The proportion of CD4+ T
      cells able to relocalize LAT or Vav, or to relocate cytoplasmic NT-AT (NF-ATc)
      from cytoplasm to nucleus, declines about 2-fold in aged mice. The decline in LAT
      relocalization is accompanied by a similar decline in tyrosine phosphorylation of
      LAT in CD4 cells stimulated by CD3/CD4 cross-linking. Two-color experiments show
      that LAT redistribution is strongly associated with relocalization of both NF-ATc
      and protein kinase C-theta among individual cells. LAT migration to the
      immunological synapse depends on actin polymerization as well as on activity of
      Src family kinases, but aging leads to only a small change in the percentage of
      CD4 cells that redistribute F-actin to the site of APC contact. These results
      suggest that defects in the ability of T cells from aged donors to move kinase
      substrates and coupling factors, including LAT and Vav, into the T cell/APC
      contact region may contribute to the decline with age in NF-ATc-dependent gene
      expression, and thus to defects in T cell clonal expansion.

PMID- 10903723
TI  - Nitric oxide induces thymocyte apoptosis via a caspase-1-dependent mechanism.
AB  - We previously showed that NO induces apoptosis in thymocytes via a p53-dependent
      pathway. In the present study, we investigated the role of caspases in this
      process. The pan-caspase inhibitor, ZVAD-fmk, and the caspase-1 inhibitor, Ac
      YVAD-cho, both inhibited NO-induced thymocyte apoptosis in a dose-dependent
      manner, whereas the caspase-3 inhibitor, Ac-DEVD-cho, had little effect even at
      concentrations up to 500 microM. ZVAD-fmk and Ac-YVAD-cho were able to inhibit
      apoptosis when added up to 12 h, but not 16 h, after treatment with the NO donor
      S-nitroso-N-acetyl penicillamine (SNAP). Caspase-1 activity was up-regulated at 4
      h and 8 h and returned to baseline by 24 h; caspase-3 activity was not detected.
      Cytosolic fractions from SNAP-treated thymocytes cleaved the inhibitor of caspase
      activated deoxyribonuclease. Such cleavage was completely blocked by Ac-YVAD-cho,
      but not by Ac-DEVD-cho or DEVD-fmk. Poly(ADP-ribose) polymerase (PARP) was also
      cleaved in thymocytes 8 h and 12 h after SNAP treatment; addition of Ac-YVAD-cho
      to the cultures blocked PARP cleavage. Furthermore, SNAP induced apoptosis in 44%
      of thymocytes from wild-type mice; thymocytes from caspase-1 knockout mice were
      more resistant to NO-induced apoptosis. These data suggest that NO induces
      apoptosis in thymocytes via a caspase-1-dependent but not caspase-3-dependent
      pathway. Caspase-1 alone can cleave inhibitor of caspase-activated
      deoxyribonuclease and lead to DNA fragmentation, thus providing a novel pathway
      for NO-induced thymocyte apoptosis.

PMID- 10903725
TI  - Expression of a functional Fc epsilon RI on rat eosinophils and macrophages.
AB  - Besides its crucial role in type I hypersensitivity reactions, IgE is involved in
      anti-parasite immunity. This role has been clearly demonstrated in both human and
      rat schistosomiasis, but remains controversial in the mouse. Since the cellular
      distribution of the high affinity IgE receptor, Fc epsilon RI, differs in humans
      and mice, it might explain the differences in effector function of IgE between
      the two species. In humans, eosinophils and macrophages induce IgE-dependent
      cytotoxicity toward Schistosoma mansoni larvae, which involves Fc epsilon RI in
      the case of eosinophils. In the present study, we have investigated the
      expression and function of Fc epsilon RI in rat eosinophils and macrophages. We
      demonstrate, by flow cytometry, fluorescence microscopy, and western blot
      analysis, that in rats, as in humans, a functional alpha gamma 2 trimeric Fc
      epsilon RI is expressed on eosinophils and macrophages. We also show that these
      two cell types can induce IgE-mediated, Fc epsilon RI-dependent cellular
      cytotoxicity toward schistosomula. These results thus provide a molecular basis
      for the differences observed between rat and mouse regarding IgE-mediated anti
      parasite immunity.

PMID- 10903724
TI  - Follicular dendritic cells carry MHC class II-expressing microvesicles at their
      surface.
AB  - Follicular dendritic cells (FDCs) present in lymphoid follicles play a critical
      role in germinal center reactions. They trap native Ags in the form of immune
      complexes providing a source for continuous stimulation of specific B
      lymphocytes. FDCs have been reported to express MHC class II molecules,
      suggesting an additional role in the presentation of not only native, but also
      processed Ag in the form of peptide-loaded MHC class II. Adoptive bone marrow
      transfer experiments have shown that MHC class II molecules are only passively
      acquired. Up to now the origin of these MHC class II molecules was not clear.
      Here we show by cryoimmunogold electron microscopy that MHC class II molecules
      are not present at the plasma membrane of FDCs. In contrast, microvesicles
      attached to the FDC surface contain MHC class II and other surface proteins not
      expressed by FDCs themselves. The size and marker profiles of these microvesicles
      resemble exosomes. Exosomes, which are secreted internal vesicles from
      multivesicular endosomes, have been shown earlier to stimulate proliferation of
      specific T lymphocytes in vitro, but their target in vivo remained a matter of
      speculation. We demonstrate here that isolated exosomes in vitro bind
      specifically to FDCs and not to other cell types, suggesting that FDCs might be a
      physiological target for exosomes.

PMID- 10903726
TI  - Glycosyl-phosphatidylinositol reanchoring unmasks distinct antigen-presenting
      pathways for CD1b and CD1c.
AB  - Human CD1 proteins present lipid and glycolipid Ags to T cells. Cellular
      trafficking patterns of CD1 proteins may determine the ability of differing
      isoforms of CD1 to acquire, bind, and present these Ags to T cells. To test this
      hypothesis, glycosyl-phosphatidylinositol (GPI)-modified variants of CD1b and
      CD1c were engineered by chimerization with a GPI modification signal sequence
      derived from decay-accelerating factor (DAF). GPI reanchoring was confirmed by
      demonstrating the phosphatidylinositol-specific phospholipase C sensitivity of
      the CD1b. DAF and CD1c. DAF fusion proteins expressed on transfectant cell
      surfaces. Using cytotoxicity and cytokine release assays as functional readouts,
      we demonstrated that CD1c. DAF is as efficient as native CD1c in presenting
      mycobacterial Ags to the human CD1c-restricted T cell line CD8-1. In contrast,
      CD1b. DAF, although also capable of presenting Ag (in this case to the CD1b
      restricted T cell line LDN5), was less efficient than its native CD1b
      counterpart. The data support the idea that CD1c. DAF maintains the capacity to
      access CD1c Ag-loading compartment(s), whereas CD1b. DAF is diverted by its GPI
      anchor away from the optimal CD1b Ag-loading compartment(s). This constitutes the
      first GPI reanchoring of CD1 proteins and provides evidence that CD1b and CD1c
      have nonoverlapping Ag-presenting pathways, suggesting that these two Ag
      presenting molecules may have distinct roles in lipid Ag presentation.

PMID- 10903727
TI  - Comprehensive assessment of determinant specificity, frequency, and cytokine
      signature of the primed CD8 cell repertoire induced by a minor transplantation
      antigen.
AB  - T cell immunity is often focused on one peptide segment of a complex protein Ag,
      with other epitopes inducing weaker, low frequency responses or no responses at
      all. Such determinant hierarchy has been well characterized for MHC class II
      restricted CD4 cell immunity, but is less well understood for class I-restricted
      CD8 cell responses. We studied class I determinant recognition in a skin
      transplant model with beta-galactosidase (beta-gal) as a minor transplantation
      Ag. CD8 T cells from C57BL/6 mice that rejected congenic C57BL/6 beta-gal
      transgenic skin were tested in enzyme-linked immunospot assays for recall
      responses to single-step, overlapping, 9-mer peptides that spanned a 94-aa region
      of the beta-gal sequence. This approach provided every possible class I
      restricted peptide for CD8 cell recognition, allowing us to define the in vivo
      frequency of CD8 cells specific for each of the 86 individual peptides. While
      four peptides were predicted to bind to the Kb or Db molecules, only one (beta
      gal96-103) actually induced an immune response. No peptides outside of the motifs
      were recognized. Tolerization to beta-gal96-103 significantly prolonged beta-gal
      transgenic skin graft survival, confirming its immune dominance. Therefore,
      single-determinant dominance characterized this CD8 cell response. The data
      demonstrate the feasibility of large-scale, comprehensive, class I determinant
      mapping, an approach that should be indispensable in measuring CD8 cell immunity
      in humans.

PMID- 10903728
TI  - The alloreactive and self-restricted CD4+ T cell response directed against a
      single MHC class II/peptide combination.
AB  - The cellular basis for allograft rejection derives from the strong T cell
      response to cells bearing foreign MHC. While it was originally assumed that
      alloreactive T cells focus their recognition on the polymorphic residues that
      differ between syngeneic and allogeneic MHC molecules, studies with MHC class I
      restricted CTL have shown that MHC-bound peptides play a critical role in
      allorecognition. It has been suggested that alloreactive T cells depend more
      strongly on interactions with the MHC molecule than with the associated peptide,
      but there is little evidence to support this idea. Here we have studied the
      alloreactive and self-restricted response directed against the class II H2-Ab
      molecule bound with a single peptide, Ep, derived from the H2-Ealpha chain. This
      MHC class II-peptide combination was a poor target and stimulator of alloreactive
      CD4+ T cell responses, indicating that MHC-bound peptides are as important for
      alloreactive CD4+ T cells as they are for alloreactive CTL. We also generated
      alloreactive T cells with exquisite specificity for the Ab/Ep complex, and
      compared their reactivity with self-restricted T cells specific for the same
      Ab/Ep complex. Our results showed that peptide-specific alloreactive T cells, as
      compared with self-restricted T cells, were more sensitive to peptide
      stimulation, but equally sensitive to amino acid substitutions in the peptide.
      These findings indicate that alloreactive and self-restricted T cells interact
      similarly with their MHC/peptide ligand.

PMID- 10903729
TI  - Indirect recognition of porcine swine leukocyte Ag class I molecules expressed on
      islets by human CD4+ T lymphocytes.
AB  - Xenotransplantation of porcine islets is considered a viable alternative
      treatment for type 1 diabetes mellitus. Therefore, we characterized human PBL
      responding to porcine islets both in vitro by coculture and in vivo using SCID
      mice reconstituted with human PBLs (HuPBL-SCID) and transplanted with porcine
      islets. T cell lines generated in vitro and graft-infiltrating T cells obtained
      from HuPBL-SCID mice were CD4+-proliferated specifically to porcine islets
      cultured with autologous APC. This proliferation was abrogated by an anti-human
      class II Ab. These T cell lines also proliferated to purified swine leukocyte Ag
      (SLA) class I molecules in the presence of self-APC, indicating that the primary
      xenoantigens recognized are peptides derived from SLA. This CD4+ T cell line
      lysed porcine islets but not splenocytes. CD4+ T cell clones with Th0, Th1, and
      Th2 cytokine profiles were isolated. The Th0 and Th1 clones lysed porcine islets,
      whereas the Th2 clone that secreted a large amount of IL-4 was not lytic. These
      results demonstrate that human T cells responding to porcine islets are primarily
      CD4+ and recognize porcine xenoantigens by the indirect Ag pathway presentation.
      These activated T cells produce cytokines that lyse islets. Furthermore, we
      demonstrate that the major porcine xenoantigens recognized are SLA class I
      molecules.

PMID- 10903730
TI  - B cell antigen receptor-induced activation of Akt promotes B cell survival and is
      dependent on Syk kinase.
AB  - Signaling through the B cell Ag receptor (BCR) is a key determinant in the
      regulation of B cell physiology. Depending on additional factors, such as
      microenvironment and developmental stage, ligation of the BCR can trigger B
      lymphocyte activation, proliferation, or apoptosis. The regulatory mechanisms
      determining B cell apoptosis and survival are not known. Using the chicken B
      lymphoma cell line DT40 as a model system, we investigated the role of the
      serine/threonine kinase Akt in B cell activation. While parental DT40 cells
      undergo apoptosis in response to BCR cross-linking, cells overexpressing Akt show
      a greatly diminished apoptotic response. By contrast, limiting the activation of
      Akt, either by inhibiting phosphatidylinositol 3-kinase or by ectopic expression
      of the phospholipid phosphatase MMAC1, results in a significant increase in the
      percentage of apoptotic cells after BCR cross-linking. Using various DT40
      knockout cell lines, we further demonstrate that the tyrosine kinase Syk is
      required for Akt activation and that Lyn tyrosine kinase inhibits Akt activation.
      Taken together, the data demonstrate that Akt plays an important role in B cell
      survival and that Akt is activated in a Syk-dependent pathway.

PMID- 10903731
TI  - IL-18 activates STAT3 in the natural killer cell line 92, augments cytotoxic
      activity, and mediates IFN-gamma production by the stress kinase p38 and by the
      extracellular regulated kinases p44erk-1 and p42erk-21.
AB  - IL-18 is a regulator of NK cell function which utilizes the serine-threonine IL
      1R-associated kinase signal transduction pathway and may activate additional not
      yet characterized signaling pathways. Here we evaluated IL-18-mediated signal
      transduction using the human NK cell line NK92 as a model. NK92 cells were shown
      by RT-PCR to express all three IL-18 receptor chains (IL-18R, accessory protein
      like chain, IL-18-binding protein). Stimulation by IL-18 strongly enhanced
      tyrosine phosphorylation of STAT3 and of the mitogen-activated protein kinases
      (MAPK) p44erk-1and p42erk-2. In contrast, STAT5 was not activated. The cytolytic
      activity of NK92 against K562 target cells, which was augmented in a dose
      dependent manner by IL-18 in the presence of trace amounts of IL-2, was
      suppressed by the specific inhibitors of MAPK pathways (PD098059 and SB203580).
      Similarly, the stimulatory effect of IL-18 on IFN-gamma protein production, given
      in conjunction with IL-2, was counteracted by inhibition of MAPK. IL-18 alone
      failed to stimulate IFN-gamma protein production despite inducing expression of
      IFN-gamma mRNA. IL-2 alone stimulated neither IFN-gamma mRNA expression nor IFN
      gamma protein production. IL-18 did not stimulate proliferation of NK92 cells,
      either alone or in combination with IL-2 or IL-12. Inhibition of the MAPK pathway
      did not significantly alter the IL-2- and IL-12-induced proliferation of NK92
      cells, whereas the Janus kinase/STAT pathway inhibitor AG490 strongly suppressed
      proliferation. MAPK activation appears to play a prominent role in IL-18
      signaling, being involved in transcription and translation of IL-18-induced IFN
      gamma mRNA and IL-18-induced cytolytic effects. In contrast, proliferation of
      NK92 cells is not affected by MAPK p44erk-1 and p42erk-2.

PMID- 10903732
TI  - Impaired natural killing of MHC class I-deficient targets by NK cells expressing
      a catalytically inactive form of SHP-1.
AB  - NK cell function is negatively regulated by MHC class I-specific inhibitory
      receptors. Transduction of the inhibitory signal involves protein tyrosine
      phosphatases such as SHP-1 (SH2-containing protein tyrosine phosphatase-1). To
      investigate the role of SHP-1 for NK cell development and function, we generated
      mice expressing a catalytically inactive, dominant-negative mutant of SHP-1
      (dnSHP-1). In this paper we show that expression of dnSHP-1 does not affect the
      generation of NK cells even though MHC receptor-mediated inhibition is partially
      impaired. Despite this defect, these NK cells do not kill syngeneic, normal
      target cells. In fact dnSHP-1-expressing NK cells are hyporesponsive toward MHC
      deficient target cells, suggesting that non-MHC-specific NK cell activation is
      significantly reduced. In contrast, these NK cells mediate Ab-dependent cell
      mediated cytotoxicity and prevent the engraftment with beta2-microglobulin
      deficient bone marrow cells. A similar NK cell phenotype is observed in viable
      motheaten (mev) mice, which show reduced SHP-1 activity due to a mutation in the
      Shp-1 gene. In addition, NK cells in both mouse strains show a tendency to
      express more inhibitory MHC-specific Ly49 receptors. Our results demonstrate the
      importance of SHP-1 for the generation of functional NK cells, which are able to
      react efficiently to the absence of MHC class I molecules from normal target
      cells. Therefore, SHP-1 may play an as-yet-unrecognized role in some NK cell
      activation pathways. Alternatively, a reduced capacity to transduce SHP-1
      dependent inhibitory signals during NK cell development may be compensated by the
      down-modulation of NK cell triggering pathways.

PMID- 10903733
TI  - TNF receptor family member BCMA (B cell maturation) associates with TNF receptor
      associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c
      Jun N-terminal kinase, and p38 mitogen-activated protein kinase.
AB  - BCMA (B cell maturation) is a nonglycosylated integral membrane type I protein
      that is preferentially expressed in mature B lymphocytes. Previously, we reported
      in a human malignant myeloma cell line that BCMA is not primarily present on the
      cell surface but lies in a perinuclear structure that partially overlaps the
      Golgi apparatus. We now show that in transiently or stably transfected cells,
      BCMA is located on the cell surface, as well as in a perinulear Golgi-like
      structure. We also show that overexpression of BCMA in 293 cells activates NF
      kappa B, Elk-1, the c-Jun N-terminal kinase, and the p38 mitogen-activated
      protein kinase. Coimmunoprecipitation experiments performed in transfected cells
      showed that BCMA associates with TNFR-associated factor (TRAF) 1, TRAF2, and
      TRAF3 adaptor proteins. Analysis of deletion mutants of the intracytoplasmic tail
      of BCMA showed that the 25-aa protein segment, from position 119 to 143,
      conserved between mouse and human BCMA, is essential for its association with the
      TRAFs and the activation of NF-kappa B, Elk-1, and c-Jun N-terminal kinase. BCMA
      belongs structurally to the TNFR family. Its unique TNFR motif corresponds to a
      variant motif present in the fourth repeat of the TNFRI molecule. This study
      confirms that BCMA is a functional member of the TNFR superfamily. Furthermore,
      as BCMA is lacking a "death domain" and its overexpression activates NF-kappa B
      and c-Jun N-terminal kinase, we can reasonably hypothesize that upon binding of
      its corresponding ligand BCMA transduces signals for cell survival and
      proliferation.

PMID- 10903734
TI  - Insulin-like growth factor 1 promotes cord blood T cell maturation and inhibits
      its spontaneous and phytohemagglutinin-induced apoptosis through different
      mechanisms.
AB  - Functional immaturity of neonatal T cells is related to their immature phenotype,
      with the majority of neonatal T cells of naive (CD45RA+) T cells. The progression
      of T cells from naive cells to effector cells is dependent on the survival of Ag
      specific T cells and their resistance to apoptosis. In this study, we showed for
      the first time that insulin-like growth factor 1 (IGF-1) converted cord blood
      CD45RA+ T cells to CD45RO+ T cells and inhibited cord blood T cell apoptosis. We
      found cord blood T cells stimulated with PHA would result in gradual loss of
      CD45RA and gain of CD45RO expression. IGF-1 further increased the loss of CD45RA
      and enhanced CD45RO expression in PHA-stimulated cord blood T cells. In addition,
      IGF-1 prevented cord blood T cells from spontaneous apoptosis through a mechanism
      other than Fas/FasL. In PHA-activated cord blood T cells, IGF-1 prevented both
      naive (CD45RA+) and memory/mature (CD45RO+) T cells from apoptosis. Moreover,
      cord blood T cells cultured with IGF-1 and PHA had a higher resistance to anti
      Fas-induced apoptosis as compared with PHA-activated cord blood T cells. IGF-1
      also significantly inhibited PHA-induced Fas expression on cord blood T cells.
      These results demonstrate that IGF-1 promotes the maturation and maintains the
      survival of cord blood T cells. Its antiapoptotic effect in PHA-activated cord
      blood T cells may be mediated through the down-regulation of Fas expression.

PMID- 10903735
TI  - Fas ligand-induced c-Jun kinase activation in lymphoid cells requires extensive
      receptor aggregation but is independent of DAXX, and Fas-mediated cell death does
      not involve DAXX, RIP, or RAIDD.
AB  - Jun kinase signaling can be elicited by death receptor activation, but the
      mechanism and significance of this event are still unclear. It has been reported
      that cross-linking Abs to Fas trigger c-Jun N-terminal kinase (JNK) signaling via
      caspase-mediated activation of MEKK1 (JNK kinase kinase), elevation of ceramide
      levels or by recruitment of death domain associated protein (DAXX) to Fas. The
      effect of physiological ligand for Fas on JNK signaling was never investigated,
      although evidence is accumulating that Fas ligand is able to induce cellular
      responses distinct from those evoked by Ab-mediated cross-linking of Fas.
      Therefore, we investigated the effect of Fas ligand on JNK signaling. Like its
      ability to induce cell death, Fas ligand reliably activated JNK only upon
      extensive aggregation of the receptor. Although this was partially dependent on
      caspase activation, DAXX was not required. DAXX and other death receptor
      associated proteins, which have been reported to bind directly or indirectly to
      Fas, such as receptor interacting protein (RIP) and RIP-associated ICH-1/CED-3
      homologous protein with a death domain (RAIDD), were shown to be dispensable for
      Fas ligand-induced apoptosis.

PMID- 10903736
TI  - Src homology region 2 (SH2) domain-containing phosphatase-1 dephosphorylates B
      cell linker protein/SH2 domain leukocyte protein of 65 kDa and selectively
      regulates c-Jun NH2-terminal kinase activation in B cells.
AB  - Src homology region 2 (SH2) domain-containing phosphatase-1 (SHP-1) is a
      cytosolic protein tyrosine phosphatase containing two SH2 domains in its NH2
      terminus. That immunological abnormalities of the motheaten and viable motheaten
      mice are caused by mutations in the gene encoding SHP-1 indicates that SHP-1
      plays important roles in lymphocyte differentiation, proliferation, and
      activation. To elucidate molecular mechanisms by which SHP-1 regulates BCR
      mediated signal transduction, we determined SHP-1 substrates in B cells using the
      substrate-trapping approach. When the phosphatase activity-deficient form of SHP
      1, in which the catalytic center cysteine (C453) was replaced with serine (SHP-1
      C/S), was introduced in WEHI-231 cells, tyrosine phosphorylation of a protein of
      about 70 kDa was strongly enhanced. Immunoprecipitation and Western blot analyses
      revealed that this protein is the B cell linker protein (BLNK), also named SH2
      domain leukocyte protein of 65 kDa, and that upon tyrosine phosphorylation BLNK
      binds to SHP-1-C/S in vitro. In vitro kinase assays demonstrated that
      hyperphosphorylation of BLNK in SHP-1-C/S-expressing cells was not due to
      enhanced activity of Lyn or Syk. Furthermore, BCR-induced activation of c-Jun NH2
      terminal kinase was shown to be significantly enhanced in SHP-1-C/S
      transfectants. Taken collectively, our results suggest that BLNK is a
      physiological substrate of SHP-1 in B cells and that SHP-1 selectively regulates
      c-Jun NH2-terminal kinase activation.

PMID- 10903737
TI  - CTLA-4 (CD152) can inhibit T cell activation by two different mechanisms
      depending on its level of cell surface expression.
AB  - CTLA-4 (CD152) engagement results in down-regulation of T cell activation. Two
      mechanisms have been postulated to explain CTLA-4 inhibition of T cell
      activation: negative signaling and competitive antagonism of CD28:B7-mediated
      costimulation. We assessed the contributions of these two mechanisms using a
      panel of T cell lines expressing human CTLA-4 with mutations in the cytoplasmic
      region. Under conditions of B7-independent costimulation, inhibition of IL-2
      production following CTLA-4 engagement required the CTLA-4 cytoplasmic region. In
      contrast, under B7-dependent costimulation, inhibition of IL-2 production by CTLA
      4 engagement was directly proportional to CTLA-4 cell surface levels and did not
      require its cytoplasmic region. Thus, CTLA-4 down-regulates T cell activation by
      two different mechanisms-delivery of a negative signal or B7 sequestration-that
      are operational depending on the levels of CTLA-4 surface expression. These two
      mechanisms may have distinct functional outcomes: rapid inhibition of T cell
      activation or induction of T cell anergy.

PMID- 10903738
TI  - IFN-gamma inhibits presentation of a tumor/self peptide by CD8 alpha- dendritic
      cells via potentiation of the CD8 alpha+ subset.
AB  - Using an in vivo model of tumor/self peptide presentation for induction of class
      I-restricted skin test reactivity, we have previously shown that a minority
      population of CD8+ dendritic cells (DC) negatively regulates the induction of T
      cell reactivity by peptide-loaded CD8- DC in DBA/2 mice. However, the CD8-
      fraction can be primed by IL-12 to overcome inhibition by the CD8+ subset when
      the two types of DC are cotransferred into recipient hosts. We report here that
      exposure of CD8+ DC to IFN-gamma greatly enhances their inhibitory activity on Ag
      presentation by the other subset, blocking the ability of IL-12-treated CD8- DC
      to overcome suppression. In contrast, IFN-gamma has no direct effects on the APC
      function of the latter cells and does not interfere with IL-12 signaling. The
      negative regulatory effect triggered by IFN-gamma in CD8+ DC appears to involve
      interference with tryptophan metabolism in vivo. Through tryptophan depletion
      affecting T cell responses, IFN-gamma acting on CD8+ DC may thus contribute to
      regulation of immunity to tumor/self peptides presented by the CD8- subset.

PMID- 10903739
TI  - T cell development in TCR beta enhancer-deleted mice: implications for alpha beta
      T cell lineage commitment and differentiation.
AB  - T cell differentiation in the mouse thymus is an intricate, highly coordinated
      process that requires the assembly of TCR complexes from individual components,
      including those produced by the precisely timed V(D)J recombination of TCR genes.
      Mice carrying a homozygous deletion of the TCR beta transcriptional enhancer (E
      beta) demonstrate an inhibition of V(D)J recombination at the targeted TCR beta
      locus and a block in alpha beta T cell differentiation. In this study, we have
      characterized the T cell developmental defects resulting from the E beta-/-
      mutation, in light of previously reported results of the analyses of TCR beta
      deficient (TCR beta-/-) mice. Similar to the latter mice, production of TCR beta
      chains is abolished in the E beta-/- animals, and under these conditions
      differentiation into cell-surface TCR-, CD4+CD8+ double positive (DP) thymocytes
      depends essentially on the cell-autonomous expression of TCR delta-chains and,
      most likely, TCR gamma-chains. However, contrary to previous reports using TCR
      beta-/- mice, a minor population of TCR gamma delta+ DP thymocytes was found
      within the E beta-/- thymi, which differ in terms of T cell-specific gene
      expression and V(D)J recombinase activity, from the majority of TCR-, alpha beta
      lineage-committed DP thymocytes. We discuss these data with respect to the
      functional role of E beta in driving alpha beta T cell differentiation and the
      mechanism of alpha beta T lineage commitment.

PMID- 10903740
TI  - The p38 mitogen-activated protein kinase is required for IL-12-induced IFN-gamma
      expression.
AB  - IL-12 is a central immunoregulatory cytokine that promotes cell-mediated immune
      responses and the differentiation of naive CD4+ cells into Th1 cells. We and
      others have demonstrated that the Stat4 is critical for IFN-gamma production by
      activated T cells and Th1 cells. However, several studies have suggested that
      other pathways may be involved in IL-12-stimulated IFN-gamma expression. In this
      report we demonstrate that IL-12 activates mitogen-activated protein kinase
      kinase 3/6 (MKK) and p38 mitogen-activated protein kinase (MAPK), but not p44/42
      (ERK) or stress-activated protein kinase/c-Jun N-terminal kinase MAPK. The
      activation of p38 MAPK is required for normal induction of IFN-gamma mRNA and IFN
      gamma secretion by IL-12 in activated T cells and Th1 cells. Importantly, IL-12
      stimulated p38 MAPK effector functions occur through a Stat4-independent
      mechanism and correlate with increased serine phosphorylation of activating
      transcription factor-2. The requirement for p38 MAPK in IL-12 function suggests
      that this pathway may be an important in vivo target for the anti-inflammatory
      actions of p38 MAPK inhibitors.

PMID- 10903741
TI  - Functional involvement of E-cadherin in TGF-beta 1-induced cell cluster formation
      of in vitro developing human Langerhans-type dendritic cells.
AB  - Epithelial Langerhans cells (LC) represent immature dendritic cells that require
      TGF-beta 1 stimulation for their development. Little is known about the
      mechanisms regulating LC generation from their precursor cells. We demonstrate
      here that LC development from human CD34+ hemopoietic progenitor cells in
      response to TGF-beta 1 costimulation (basic cytokine combination GM-CSF plus TNF
      alpha, stem cell factor, and Flt3 ligand) is associated with pronounced cell
      cluster formation of developing LC precursor cells. This cell-clustering
      phenomenon requires hemopoietic progenitor cell differentiation, since it is
      first seen on day 4 after culture initiation of CD34+ cells. Cell cluster
      formation morphologically indicates progenitor cell development along the LC
      pathway, because parallel cultures set up in the absence of exogenous TGF-beta 1
      fail to form cell clusters and predominantly give rise to monocyte, but not LC,
      development (CD1a-, lysozyme+, CD14+). TGF-beta 1 costimulation of CD34+ cells
      induces neoexpression of the homophilic adhesion molecule E-cadherin in the
      absence of the E-cadherin heteroligand CD103. Addition of anti-E-cadherin mAb or
      mAbs to any of the constitutively expressed adhesion molecule (CD99, CD31, LFA-1,
      or CD18) to TGF-beta 1-supplemented progenitor cell cultures inhibits LC
      precursor cell cluster formation, and this effect is, with the exception of anti
      E-cadherin mAb, associated with inhibition of LC generation. Addition of anti-E
      cadherin mAb to the culture allows cell cluster-independent generation of LC from
      CD34+ cells. Thus, functional E-cadherin expression and homotypic cell cluster
      formation represent a regular response of LC precursor cells to TGF-beta 1
      stimulation, and cytoadhesive interactions may modulate LC differentiation from
      hemopoietic progenitor cells.

PMID- 10903742
TI  - Increased frequency of surface IgA-positive plasma cells in the intestinal lamina
      propria and decreased IgA excretion in hyper IgA (HIGA) mice, a murine model of
      IgA nephropathy with hyperserum IgA.
AB  - Because abnormalities of mucosal immunity have been suggested in human IgA
      nephropathy, we examined the involvement of mucosal immunity in IgA deposition to
      the kidney in hyper IgA (HIGA) mice, which was established as a mouse model for
      human IgA nephropathy with hyperserum IgA. The number of surface IgA+B220-
      lymphocytes in the intestinal lamina propria (LP) of HIGA mice increased 2.7-fold
      at 30 wk of age as compared with those at 10 wk of age, whereas normal mice did
      not show such increase. The surface IgA+B220- LP lymphocytes spontaneously
      secreted IgA in culture. Morphological studies showed that the surface IgA+B220-
      lymphocytes of murine intestinal LP are identical with plasma cells (PCs). About
      20% of IgA+B220- PC in LP expressed both Mac-1 and CD19, suggesting that they may
      derive from peritoneal B-1 cells. Cell cycle study on intestinal IgA-PCs using
      bromodeoxyuridine revealed no difference between HIGA mice and normal mice,
      suggesting that the high frequency of IgA-producing PCs in HIGA mice is not due
      to enhanced proliferation or prolonged survival of IgA-producing PCs in LP. In
      addition, IgA secretion into the gut lumen of HIGA mice decreased drastically (to
      one forth) with aging. These data suggest that the increased number of intestinal
      IgA-producing PCs and the down-regulation of IgA excretion into the intestinal
      lumen might synergistically contribute to the hyperserum IgA in HIGA mice and
      resultant IgA deposition to the kidney.

PMID- 10903743
TI  - IL-4 enhances keratinocyte expression of CXCR3 agonistic chemokines.
AB  - IFN-induced protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and
      IFN-inducible T-cell alpha-chemoattractant (I-TAC) belong to the non-glutamate
      leucine-arginine motif CXC chemokine family and act solely through the CXCR3
      receptor for potent attraction of T lymphocytes. In this study, we evaluated the
      capacity of the T cell-derived cytokines IL-4, IL-10, and IL-17 to modulate IP
      10, Mig, and I-TAC in cultured human keratinocytes and CXCR3 expression in T
      cells from allergic contact dermatitis (ACD). IL-4, but not IL-10 or IL-17,
      significantly up-regulated IFN-gamma- or TNF-alpha-induced IP-10, Mig, and I-TAC
      mRNA accumulation in keratinocytes and increased the levels of IP-10 and Mig in
      keratinocyte supernatants. Immunohistochemistry of skin affected by ACD revealed
      that >70% of infiltrating cells were reactive for CXCR3 and that CXCR3 staining
      colocalized in CD4+ and CD8+ T cells. Nickel-specific CD4+ and CD8+ T cell lines
      established from ACD skin produced IFN-gamma and IL-4 and expressed moderate to
      high levels of CXCR3. Finally, CXCR3 agonistic chemokines released by stimulated
      keratinocytes triggered calcium mobilization in skin-derived nickel-specific CD4+
      T cells and promoted their migration, with supernatant from keratinocyte cultures
      stimulated with IFN-gamma and IL-4 attracting more efficaciously than supernatant
      from keratinocytes activated with IFN-gamma alone. In conclusion, IL-4 exerts a
      proinflammatory function on keratinocytes by potentiating IFN-gamma and TNF-alpha
      induction of IP-10, Mig, and I-TAC, which in turn may determine a prominent
      recruitment of CXCR3+ T lymphocytes at inflammatory reaction sites.

PMID- 10903744
TI  - Impaired secretion of rat mannose-binding protein resulting from mutations in the
      collagen-like domain.
AB  - Serum mannose-binding protein (MBP) or mannose-binding lectin initiates the
      lectin branch of the innate immune response by binding to the surface of
      potentially pathogenic microorganisms and initiating complement fixation through
      an N-terminal collagen-like domain. Mutations in this region of human MBP are
      associated with immunodeficiency resulting from a reduction in the ability of the
      mutant MBPs to fix complement as well as from reduced serum concentrations.
      Inefficient secretion of the mutant proteins, which is one possible cause of the
      reduced serum levels, has been investigated using a mammalian expression system
      in which each of the naturally occurring human mutations has been recreated in
      rat serum MBP. The mutations Gly25-->Asp and Gly28-->Glu disrupt the disulfide
      bonding arrangement of the protein and cause at least a 5-fold increase in the
      half-time of secretion of MBP compared with wild-type rat serum MBP. A similar
      phenotype, including a 3-fold increase in the half-time of secretion, disruption
      of the disulfide bonding arrangement, and inefficient complement fixation, is
      observed when nearby glucosylgalactosyl hydroxylysine residues at positions 27
      and 30 are replaced with arginine residues. The results suggest that defective
      secretion resulting from structural changes in the collagen-like domain is likely
      to be a contributory factor for MBP immunodeficiency.

PMID- 10903745
TI  - Identification of class II transcriptional activator-induced genes by
      representational difference analysis: discoordinate regulation of the DN alpha/DO
      beta heterodimer.
AB  - Class II transcriptional activator (CIITA) is a master regulator of MHC class II
      genes, including DR, DP, and DQ, and MHC class II-associated genes DM and
      invariant chain. To determine the repertoire of genes that is regulated by CIITA
      and to identify uncharacterized CIITA-inducible genes, we used representational
      difference analysis. Representational difference analysis screens for
      differentially expressed transcripts. All CIITA-induced genes were MHC class II
      related. We have identified the alpha subunit, DN alpha, of the class II
      processing factor DO as an additional CIITA-inducible gene. Northern analysis
      confirmed that DN alpha is induced by IFN-gamma in 2fTGH fibrosarcoma cells, and
      CIITA is necessary for high-level expression in B cells. The beta subunit, DO
      beta, is not inducible in fibrosarcoma cells by IFN-gamma or exogenous CIITA
      expression. Moreover, in contrast to other class II genes, DO beta expression
      remains high in the absence of CIITA in B cells. The promoters for DN alpha and
      DO beta contain the highly conserved WXY motifs, and, like other class II genes,
      expression of both DN alpha and DO beta requires RFX. These findings demonstrate
      that both DN alpha and DO beta are regulated by RFX. However, DN alpha is defined
      for the first time as a CIITA-inducible gene, and DO beta as a MHC class II gene
      whose expression is independent of CIITA.

PMID- 10903746
TI  - The adaptor protein Gads (Grb2-related adaptor downstream of Shc) is implicated
      in coupling hemopoietic progenitor kinase-1 to the activated TCR.
AB  - The hemopoietic-specific Gads (Grb2-related adaptor downstream of Shc) adaptor
      protein possesses amino- and carboxyl-terminal Src homology 3 (SH3) domains
      flanking a central SH2 domain and a unique region rich in glutamine and proline
      residues. Gads functions to couple the activated TCR to distal signaling events
      through its interactions with the leukocyte-specific signaling proteins SLP-76
      (SH2 domain-containing leukocyte protein of 76 kDa) and LAT (linker for activated
      T cells). Expression library screening for additional Gads-interacting molecules
      identified the hemopoietic progenitor kinase-1 (HPK1), and we investigated the
      HPK1-Gads interaction within the DO11.10 murine T cell hybridoma system. Our
      results demonstrate that HPK1 inducibly associates with Gads and becomes tyrosine
      phosphorylated following TCR activation. HPK1 kinase activity is up-regulated in
      response to activation of the TCR and requires the presence of its proline-rich
      motifs. Mapping experiments have revealed that the carboxyl-terminal SH3 domain
      of Gads and the fourth proline-rich region of HPK1 are essential for their
      interaction. Deletion of the fourth proline-rich region of HPK1 or expression of
      a Gads SH2 mutant in T cells inhibits TCR-induced HPK1 tyrosine phosphorylation.
      Together, these data suggest that HPK1 is involved in signaling downstream from
      the TCR, and that SH2/SH3 domain-containing adaptor proteins, such as Gads, may
      function to recruit HPK1 to the activated TCR complex.

PMID- 10903747
TI  - Aberrant trafficking of the B cell receptor Ig-alpha beta subunit in a B lymphoma
      cell line.
AB  - The B cell Ag receptor (BCR) has two important functions: first, it binds and
      takes up Ag for presentation to T lymphocytes; and second, it transmits signals
      that regulate B cell development. Normal expression of the BCR requires the
      association of the Ag binding subunit, membrane IgM (mIgM), with the signaling
      component, the Ig-alpha beta heterodimer. After assembly in the endoplasmic
      reticulum, the intact BCR travels through the secretory pathway to the cell
      surface. In this paper, we report two variants of the B lymphoma cell lines, WEHI
      279 and WEHI 231, that have both lost the ability to express mu heavy chain and
      consequently do not express mIgM. However, these variants do express the Ig-alpha
      beta heterodimer. In one variant, WEHI 279*, the Ig-alpha beta remained trapped
      intracellularly in the absence of mIgM. The other variant, 303.1.5.LM, expressed
      an aberrantly glycosylated Ig-alpha beta on the cell surface that was capable of
      signaling after cross-linking with anti-Ig-beta Abs. Further characterization
      uncovered a point mutation in the 303.1.5.LM mb1 gene that would change a proline
      for a leucine in the extracellular domain of Ig-alpha. The 303.1.5.LM Ig-alpha
      beta could not associate with a wild-type mIgM after mu heavy chain was
      reconstituted by DNA transfection. Thus, this mutation could define a region of
      the Ig-alpha polypeptide that is important for recognition by the endoplasmic
      reticulum quality control system, for association with glycosylating enzymes, and
      for the association of Ig-alpha beta subunits with mIgM subunits to create a
      complete BCR complex.

PMID- 10903748
TI  - The role of cell surface receptors in the activation of human B cells by
      phosphorothioate oligonucleotides.
AB  - Phosphorothioate oligodeoxynucleotides (sODN) containing the CpG motif or TCG
      repeats induce T cell-independent polyclonal activation of human B cells. To
      elucidate the mechanism of this response, the role of cell surface receptors was
      investigated. Sepharose beads coated with stimulatory but not nonstimulatory
      sODNs induced B cell proliferation comparably with soluble sODNs. The B cell
      stimulatory activity of Sepharose-bound sODN did not result from free sODN
      released from the beads since media incubated with coated beads were inactive.
      Using FITC-labeled sODNs as probes, binding to human B cells could be detected by
      flow cytometry. Binding was rapid, saturable, initially temperature independent,
      but with a rapid off-rate. Competition studies indicated that both stimulatory
      sODNs and minimally stimulatory sODNs bound to the same receptor. By contrast,
      phosphodiester oligonucleotides with the same nucleotide sequence as sODNs and
      bacterial DNA inhibited the binding of sODNs to B cells minimally. Charge
      appeared to contribute to the binding of sODNs to B cells since binding of sODNs
      was competitively inhibited by negatively charged molecules, including fucoidan,
      poly I, and polyvinyl sulfate. These data indicate that human B cells bind sODNs
      by a receptor-mediated mechanism that is necessary but not sufficient for
      polyclonal activation.

PMID- 10903749
TI  - Bone-marrow chimeras reveal hemopoietic and nonhemopoietic control of resistance
      to experimental Lyme arthritis.
AB  - Both genetic resistance and susceptibility to development of experimental Lyme
      arthritis are mediated by the innate immune response. To determine whether this
      process is mainly controlled by hemopoietic or nonhemopoietic cells, we created
      bone marrow (BM) chimeric mice between arthritis-resistant DBA/2J (DBA) and
      arthritis-susceptible C3H/HeJ (C3H) mice and infected them with Borrelia
      burgdorferi. Both sets of BM chimeric mice, C3H donors into DBA recipients (C-
      >D) and DBA donors into C3H recipients (D-->C), as well as DBA sham chimeric mice
      (D-->D) were resistant to the development of experimental Lyme arthritis as
      measured by ankle swelling and arthritis severity scores. Only the C3H sham
      chimeric mice (C-->C) developed severe arthritis. These results indicate that
      independent and nonoverlapping mechanisms exist in hemopoietic and nonhemopoietic
      cellular compartments that can provide protection against arthritic pathology.

PMID- 10903750
TI  - The complexity of protective immunity against liver-stage malaria.
AB  - Sterile protective immunity against challenge with Plasmodium spp. sporozoites
      can be induced in multiple model systems and humans by immunization with
      radiation-attenuated Plasmodium spp. sporozoites. The infected hepatocyte has
      been established as the primary target of this protection, but the underlying
      mechanisms have not been completely defined. Abs, CD8+ T cells, CD4+ T cells,
      cytokines (including IFN-gamma and IL-12), and NO have all been implicated as
      critical effectors. Here, we have investigated the mechanisms of protective
      immunity induced by immunization with different vaccine delivery systems
      (irradiated sporozoites, plasmid DNA, synthetic peptide/adjuvant, and multiple Ag
      peptide) in genetically distinct inbred strains, genetically modified mice, and
      outbred mice. We establish that there is a marked diversity of T cell-dependent
      immune responses that mediate sterile protective immunity against liver-stage
      malaria. Furthermore, we demonstrate that distinct mechanisms of protection are
      induced in different strains of inbred mice by a single method of immunization,
      and in the same strain by different methods of immunization. These data
      underscore the complexity of the murine host response to a parasitic infection
      and suggest that an outbred human population may behave similarly. Data
      nevertheless suggest that a pre-erythrocytic-stage vaccine should be designed to
      induce CD8+ T cell- and IFN-gamma-mediated immune responses and that IFN-gamma
      responses may represent an in vitro correlate of pre-erythrocytic-stage
      protective immunity.

PMID- 10903751
TI  - Chlamydia trachomatis infection of epithelial cells induces the activation of
      caspase-1 and release of mature IL-18.
AB  - Th1 cells that secrete IFN-gamma are particularly important in protective
      immunity against intracellular pathogens, including chlamydiae, and IL-18
      together with IL-12 are strong inducers of IFN-gamma secretion by CD4 T cells.
      Because epithelial cells are known to synthesize IL-18, we investigated the
      effects of Chlamydia trachomatis infection of human epithelial cell lines on IL
      18 secretion. We confirmed that several human epithelial cell lines
      constitutively express pro-IL-18 and that C. trachomatis infection causes cells
      to secrete mature IL-18. This was observed for several different serovars and
      biovars of C. trachomatis. Chlamydia-induced secretion of IL-18 from epithelial
      cells was regulated at the posttranscriptional level and was dependent on the
      activation of caspase-1. IL-1alpha or other secreted factor(s) from chlamydia
      infected epithelial cells as well as chlamydial structural component(s) were not
      involved in inducing IL-18 secretion. Activation of caspase-1 and increased
      secretion of mature IL-18 was correlated with chlamydial, but not with host
      protein synthesis. In contrast to epithelial cell lines, fibroblast cell lines
      constitutively expressed much lower levels of pro-IL-18 and did not secrete
      mature IL-18 after chlamydial infection even though caspase-1 was activated.
      Taken together, the results suggest that a chlamydia-derived factor(s) is
      essential for the secretion of mature IL-18 through caspase-1 activation in
      infected epithelial cells.

PMID- 10903752
TI  - Soluble CD8 attenuates cytotoxic T cell responses against replication-defective
      adenovirus affording transprotection of transgenes in vivo.
AB  - The T cell coreceptor, CD8, enhances T cell-APC interactions. Because soluble
      CD8alpha homodimers can antagonize CD8 T cell activation in vitro, we asked
      whether secretion of soluble CD8 would effect cytotoxic T cell responses in vivo.
      Production of soluble CD8 by a replication-defective adenovirus vector allowed
      persistent virus expression for up to 5 mo in C57BL/6 mice and protected a second
      foreign transgene from rapid deletion. Soluble CD8 selectively inhibited CD8 T
      cell proliferation and IFN-gamma production and could also attenuate peptide
      specific CD8 T cell responses in vivo. These finding suggest that gene vector
      delivery of soluble CD8 may have therapeutic applications.

PMID- 10903753
TI  - Pulmonary mononuclear cell responses to antigens of Mycobacterium tuberculosis in
      healthy household contacts of patients with active tuberculosis and healthy
      controls from the community.
AB  - Protective immunity against Mycobacterium tuberculosis requires CD4+ lymphocyte
      mediated immune responses and IFN-gamma activity. As the primary portal of entry
      of M. tuberculosis is the lung, pulmonary immune responses against multiple M.
      tuberculosis Ags were compared between both M. tuberculosis-exposed tuberculin
      skin test-positive healthy household contacts (HHC) of patients with active
      sputum smear and culture-positive tuberculosis and tuberculin skin test-positive
      healthy control individuals from the community (CC). Frequencies of M.
      tuberculosis Ag-specific IFN-gamma-producing cells, IFN-gamma concentrations in
      culture supernatants, and DNA synthesis in bronchoalveolar cells (BAC) and PBMC
      were studied in HHC (n = 10) and CC (n = 15). Using enzyme-linked immunospot
      assay we found higher frequencies of IFN-gamma-producing cells with specificity
      to M. tuberculosis-secreted Ag 85 (Ag 85) in BAC from HHC than in BAC from CC (p
      < 0.022) and relative to autologous PBMC, indicating compartmentalization of Ag
      85-specific cells to the lungs. Further, IFN-gamma-producing cells with
      specificity to components A and B of Ag 85 were specifically compartmentalized to
      the lungs in HHC (p < 0. 05). IFN-gamma concentrations in culture supernatants of
      BAC and Ag-specific DNA synthesis were low and comparable in the two subject
      groups. Increased immune responses to Ag 85 at the site of repeated exposure to
      M. tuberculosis (the lung) may represent an important component of protective
      immunity against M. tuberculosis. Correlates of protective immunity against M.
      tuberculosis are required for assessment of the efficiency of anti-tuberculous
      vaccines.

PMID- 10903754
TI  - Bactericidal and tumoricidal activities of synthetic peptides derived from
      granulysin.
AB  - Granulysin, a 9-kDa protein localized to human CTL and NK cell granules, is
      cytolytic against tumor cells and microbes. Molecular modeling predicts that
      granulysin is composed of five alpha-helices separated by short loop regions. In
      this report, synthetic peptides corresponding to the linear granulysin sequence
      were characterized for lytic activity. Peptides corresponding to the central
      region of granulysin lyse bacteria, human cells, and synthetic liposomes, while
      peptides corresponding to the amino or carboxyl regions are not lytic. Peptides
      corresponding to either helix 2 or helix 3 lyse bacteria, while lysis of human
      cells and liposomes is dependent on the helix 3 sequence. Peptides in which
      positively charged arginine residues are substituted with neutral glutamine
      exhibit reduced lysis of all three targets. While reduction of recombinant 9-kDa
      granulysin increases lysis of Jurkat cells, reduction of cysteine-containing
      granulysin peptides decreases lysis of Jurkat cells. In contrast, lysis of
      bacteria by recombinant granulysin or by cysteine-containing granulysin peptides
      is unaffected by reducing conditions. Jurkat cells transfected with either CrmA
      or Bcl-2 are protected from lysis by recombinant granulysin or the peptides.
      Differential activity of granulysin peptides against tumor cells and bacteria may
      be exploited to develop specific antibiotics without toxicity for mammalian
      cells.

PMID- 10903755
TI  - Purification and cloning of an apoptosis-inducing protein derived from fish
      infected with Anisakis simplex, a causative nematode of human anisakiasis.
AB  - While investigating the effect of marine products on cell growth, we found that
      visceral extracts of Chub mackerel, an ocean fish, had a powerful and dose
      dependent apoptosis-inducing effect on a variety of mammalian tumor cells. This
      activity was strikingly dependent on infection of the C. mackerel with the larval
      nematode, Anisakis simplex. After purification of the protein responsible for the
      apoptosis-inducing activity, we cloned the corresponding gene and found it to be
      a flavoprotein. This protein, termed apoptosis-inducing protein (AIP), was also
      found to possess an endoplasmic reticulum retention signal (C-terminal KDEL
      sequence) and H2O2-producing activity, indicating that we had isolated a novel
      reticuloplasimin with potent apoptosis-inducing activity. AIP was induced in fish
      only after infection with larval nematode and was localized to capsules that
      formed around larvae to prevent their migration to host tissues. Our results
      suggest that AIP may function to impede nematode infection.

PMID- 10903756
TI  - Human dendritic cells discriminate between viable and killed Toxoplasma gondii
      tachyzoites: dendritic cell activation after infection with viable parasites
      results in CD28 and CD40 ligand signaling that controls IL-12-dependent and 
      independent T cell production of IFN-gamma.
AB  - We studied how the interaction between human dendritic cells (DC) and Toxoplasma
      gondii influences the generation of cell-mediated immunity against the parasite.
      We demonstrate that viable, but not killed, tachyzoites of T. gondii altered the
      phenotype of immature DC. DC infected with viable parasites up-regulated the
      expression of CD40, CD80, CD86, and HLA-DR and down-regulated expression of
      CD115. These changes are indicative of DC activation induced by T. gondii. Viable
      and killed tachyzoites had contrasting effects on cytokine production. DC
      infected with viable T. gondii rather than DC that phagocytosed killed parasites
      induced secretion of high amounts of IFN-gamma by T cells from T. gondii
      seronegative donors. IFN-gamma production in response to DC infected with viable
      parasites required CD28 and CD40 ligand (CD40L) signaling. In addition, this IFN
      gamma response was dependent in part on IL-12 secretion. Production of IL-12 p70
      occurred after interaction between T cells and DC infected with viable T. gondii,
      but not after incubation of T cells with DC plus killed tachyzoites. IL-12
      synthesis was inhibited by blockade of CD40L signaling. IL-12-independent IFN
      gamma production required CD80/CD86-CD28 interaction and, to a lesser extent,
      CD40-CD40L signaling. Taken together, T. gondii-induced activation of human DC is
      associated with T cell production of IFN-gamma through CD40-CD40L-dependent
      release of IL-12 and through CD80/CD86-CD28 and CD40-CD40L signaling that mediate
      IFN-gamma secretion even in the absence of bioactive IL-12.

PMID- 10903757
TI  - A role for CD40-CD40 ligand interactions in the generation of type 1 cytokine
      responses in human leprosy.
AB  - The interaction of CD40 ligand (CD40L) expressed by activated T cells with CD40
      on macrophages has been shown to be a potent stimulus for the production of IL
      12, an obligate signal for generation of Th1 cytokine responses. The expression
      and interaction of CD40 and CD40L were investigated in human infectious disease
      using leprosy as a model. CD40 and CD40L mRNA and surface protein expression were
      predominant in skin lesions of resistant tuberculoid patients compared with the
      highly susceptible lepromatous group. IL-12 release from PBMC of tuberculoid
      patients stimulated with Mycobacterium leprae was partially inhibited by mAbs to
      CD40 or CD40L, correlating with Ag-induced up-regulation of CD40L on T cells.
      Cognate recognition of M. leprae Ag by a T cell clone derived from a tuberculoid
      lesion in the context of monocyte APC resulted in CD40L-CD40-dependent production
      of IL-12. In contrast, M. leprae-induced IL-12 production by PBMC from
      lepromatous patients was not dependent on CD40L-CD40 ligation, nor was CD40L up
      regulated by M. leprae. Furthermore, IL-10, a cytokine predominant in lepromatous
      lesions, blocked the IFN-gamma up-regulation of CD40 on monocytes. These data
      suggest that T cell activation in situ by M. leprae in tuberculoid leprosy leads
      to local up-regulation of CD40L, which stimulates CD40-dependent induction of IL
      12 in monocytes. The CD40-CD40L interaction, which is not evident in lepromatous
      leprosy, probably participates in the cell-mediated immune response to microbial
      pathogens.

PMID- 10903758
TI  - Urokinase receptor-deficient mice have impaired neutrophil recruitment in
      response to pulmonary Pseudomonas aeruginosa infection.
AB  - Leukocytes express both urokinase-type plasminogen activator (uPA) and the
      urokinase receptor (uPAR, CD87). Evidence in vitro has implicated uPAR as a
      modulator of beta2 integrin function, particularly CR3 (CD11b/CD18, Mac-1).
      Pseudomonas aeruginosa infection has been demonstrated to recruit neutrophils to
      the pulmonary parenchyma by a beta2 integrin-dependent mechanism. We demonstrate
      that mice deficient in uPAR (uPAR-/-) have profoundly diminished neutrophil
      recruitment in response to P. aeruginosa pneumonia compared with wild-type (WT)
      mice. The requirement for uPAR in neutrophil recruitment is independent of the
      serine protease uPA, as neutrophil recruitment in uPA-/- mice is
      indistinguishable from recruitment in WT mice. uPAR-/- mice have impaired
      clearance of P. aeruginosa compared with WT mice, as demonstrated by CFU and
      comparative histology. WT mice have diminished neutrophil recruitment to the lung
      when an anti-CD11b mAb is given before inoculation with the pathogen, while
      recruitment of uPAR-/- neutrophils is unaffected. We conclude that uPAR is
      required for the recruitment of neutrophils to the lung in response to P.
      aeruginosa pneumonia and that this requirement is independent of uPA. Further, we
      show that uPAR and CR3 act by a common mechanism during neutrophil recruitment to
      the lung in response to P. aeruginosa. This is the first report of a requirement
      for uPAR during cellular recruitment in vivo against a clinically relevant
      pathogen.

PMID- 10903759
TI  - Increased susceptibility of Stat4-deficient and enhanced resistance in Stat6
      deficient mice to infection with Trypanosoma cruzi.
AB  - Although Th1-type responses tend to be associated with resistance to Trypanosoma
      cruzi infection, mixed Th1 and Th2 cytokine responses are generally observed in
      both resistant and susceptible mice. To help clarify the role of type 1 and type
      2 cytokine responses in immunity to T. cruzi, mice with induced deficiencies in
      the Stat4 or Stat6 genes were infected with T. cruzi. As expected, Stat4-/- mice
      deficient in type 1 cytokine responses were highly susceptible to infection,
      exhibiting increased parasitemia levels relative to wild-type mice and 100%
      mortality. In contrast, parasitemia levels and survival in Stat6-deficient mice
      were not different from wild type. The type 1 and type 2 cytokine bias of Stat6-
      and Stat4-deficient mice, respectively, was confirmed by in situ
      immunocytochemical analysis of cytokine-producing cells in the tissues of
      infected mice and by subclass analysis of anti-T. cruzi serum Abs. Notably, both
      Stat4- and Stat6-deficient mice produced substantial amounts of anti-T. cruzi
      Abs. Tissues from chronically infected Stat6-deficient mice had little to no
      evidence of inflammation in the heart and skeletal muscle in contrast to wild
      type mice, which exhibited substantial inflammation. In situ PCR analysis of
      these tissues provided evidence of the persistence of T. cruzi in wild-type mice,
      but no evidence of parasite persistence in Stat6-deficient mice. These data
      suggest that type 1 T cells are required for the development of immune control to
      T. cruzi, but that type 2 T cells contribute to parasite persistence and
      increased severity of disease.

PMID- 10903760
TI  - Inducible nitric oxide synthase inhibitors suppress airway inflammation in mice
      through down-regulation of chemokine expression.
AB  - Growing evidence demonstrates that inducible NO synthase (iNOS) is induced in the
      airways of asthmatic patients. However, the precise role of NO in the lung
      inflammation is unknown. This study investigated the effect of both selective and
      nonselective iNOS inhibitors in an allergen-driven murine lung inflammation
      model. OVA challenge resulted in an accumulation of eosinophils and neutrophils
      in the airways. Expression of iNOS immunostaining in lung sections together with
      an increase in calcium-independent NOS activity in lung homogenates was also
      observed after OVA challenge. Treatment with iNOS inhibitors from the day of
      challenge to the day of sacrifice resulted in an inhibition of the inflammatory
      cell influx together with a down-regulation of macrophage inflammatory protein-2
      and monocyte chemoattractant protein-1 production. In contrast, eosinophilic and
      neutrophilic inhibition was not observed with treatment during the sensitization.
      Both treatments induced an increased production of Th2-type cytokines (IL-4 and
      IL-5) with a concomitant decrease in production of Th1-type cytokine (IFN-gamma).
      In vitro exposure of primary cultures of murine lung fibroblasts to a NO donor,
      hydroxylamine, induced a dose-dependent release of macrophage inflammatory
      protein-2 and monocyte chemoattractant protein-1. Our results suggest that lung
      inflammation after allergen challenge in mice is partially dependent on NO
      produced mainly by iNOS. NO appears to increase lung chemokine expression and,
      thereby, to facilitate influx of inflammatory cells into the airways.

PMID- 10903761
TI  - Chloroquine interferes with lipopolysaccharide-induced TNF-alpha gene expression
      by a nonlysosomotropic mechanism.
AB  - Chloroquine (CQ) is a lysosomotropic weak base with over 60 years of clinical use
      for the treatment of malaria and rheumatologic disorders. Consistent with its
      anti-inflammatory properties, CQ has been shown to interfere with TNF-alpha
      release from mononuclear phagocytes. Because it is unclear how CQ mediates these
      immunomodulatory effects, we set out to elucidate its mechanism of action. CQ
      exhibited dose-dependent inhibition of LPS-induced TNF-alpha release from human
      PBMC at therapeutically attainable concentrations. Additional studies to
      determine the specificity of this effect showed that although CQ reduced IL-1beta
      and IL-6 release, secretion of RANTES was unaffected. CQ acted by reducing TNF
      alpha mRNA accumulation without destabilizing its mRNA or interfering with NF
      kappaB nuclear translocation or p50/p65 isoform composition of DNA-binding
      complexes. Intracellular cytokine staining indicated that CQ reduced TNF-alpha
      production pretranslationally without interfering with TNF-alpha processing or
      release. We utilized bafilomycin A1 pretreatment to block the pH-dependent
      trapping of CQ in endosomes and lysosomes. Although bafilomycin A1 alone did not
      interfere with TNF-alpha expression, preincubation augmented the ability of CQ to
      reduce TNF-alpha mRNA levels, suggesting that CQ did not act by a lysosomotropic
      mechanism. Using confocal microscopy, we showed that bafilomycin A1 pretreatment
      resulted in a dramatic redistribution of quinacrine, a fluorescent congener of
      CQ, from cytoplasmic vacuoles to the nucleus. These data indicate that CQ
      inhibits TNF-alpha gene expression without altering translocation of NF-kappaB
      p50/p65 heterodimers. This dose-dependent effect occurs over a pharmacologically
      relevant concentration range and does not require pH-dependent lysosomotropic
      accumulation of CQ.

PMID- 10903762
TI  - Inhibition of human endothelial cell chemokine production by the opportunistic
      fungal pathogen Cryptococcus neoformans.
AB  - Cryptococcus neoformans is an encapsulated fungal pathogen commonly acquired by
      inhalation. Extrapulmonary dissemination can lead to infection of the bloodstream
      and various organs, most commonly resulting in meningoencephalitis. However,
      infection with C. neoformans is often characterized by a scant inflammatory
      response. The leukocyte response to infection depends in part upon a gradient of
      chemotactic factors and adhesion molecules expressed by the host vascular
      endothelium, yet the inflammatory response of human endothelial cells (EC) to C.
      neoformans has not been previously investigated. We found that incubation of
      primary human EC with C. neoformans did not induce chemokine synthesis, and
      resulted in differential inhibition of cytokine-induced IL-8, IFN-gamma-inducible
      protein-10, and monocyte chemoattractant protein-1. In contrast, C. neoformans
      had little effect on EC surface expression of the leukocyte ligand, ICAM-1, as
      determined by flow cytometry. Modulation of chemokine production was dependent on
      the chemokine under study, the inoculum of C. neoformans used, fungal viability,
      and cell-cell contact, but independent of cryptococcal strain or encapsulation.
      These observations suggest a novel mechanism whereby C. neoformans can affect EC
      function and interfere with the host inflammatory response.

PMID- 10903763
TI  - CXCR3 expression and activation of eosinophils: role of IFN-gamma-inducible
      protein-10 and monokine induced by IFN-gamma.
AB  - CXC chemokine receptor 3 (CXCR3), predominately expressed on memory/activated T
      lymphocytes, is a receptor for both IFN-gamma-inducible protein-10 (gamma IP-10)
      and monokine induced by IFN-gamma (Mig). We report a novel finding that CXCR3 is
      also expressed on eosinophils. gamma IP-10 and Mig induce eosinophil chemotaxis
      via CXCR3, as documented by the fact that anti-CXCR3 mAb blocks gamma IP-10- and
      Mig-induced eosinophil chemotaxis. gamma IP-10- and Mig-induced eosinophil
      chemotaxis are up- and down-regulated by IL-2 and IL-10, respectively.
      Correspondingly, CXCR3 protein and mRNA expressions in eosinophils are up- and
      down-regulated by IL-2 and IL-10, respectively, as detected using flow cytometry,
      immunocytochemical assay, and a real-time quantitative RT-PCR technique. gamma IP
      10 and Mig act eosinophils to induce chemotaxis via the cAMP-dependent protein
      kinase A signaling pathways. The fact that gamma IP-10 and Mig induce an increase
      in intracellular calcium in eosinophils confirms that CXCR3 exists on
      eosinophils. Besides induction to chemotaxis, gamma IP-10 and Mig also activate
      eosinophils to eosinophil cationic protein release. These results indicate that
      CXCR3-gamma IP-10 and -Mig receptor-ligand pairs as well as the effects of IL-2
      and IL-10 on them may be especially important in the cytokine/chemokine
      environment for the pathophysiologic events of allergic inflammation, including
      initiation, progression, and termination in the processes.

PMID- 10903764
TI  - Heterogeneous effects of IL-2 on collagen-induced arthritis.
AB  - IL-2 is generally considered a pro-inflammatory cytokine that exacerbates Th1
      mediated disease states, such as autoimmune arthritis. Consistent with this role
      for IL-2, recent studies from our laboratory demonstrate that IL-2 mRNA is
      markedly increased during the acute stage of collagen-induced arthritis (CIA), an
      animal model of rheumatoid arthritis. To further define the role of IL-2 in CIA,
      the levels of IL-2 protein and its receptor and the effects of IL-2
      administration were analyzed during CIA. IL-2 protein and IL-2R were
      preferentially expressed at disease onset, compared with later stages of disease.
      Administration of recombinant human IL-2 (rhIL-2) at, or just before, disease
      onset exacerbated disease; surprisingly, rhIL-2 given before disease onset
      inhibited CIA, associated with reduced cellular and humoral responses to type II
      collagen. Determination of in vivo serum levels of Th1 and Th2 cytokines in
      response to rhIL-2 treatment demonstrated that IFN-gamma, but not IL-4, was
      markedly up-regulated in response to IL-2. In mice treated with anti-IFN-gamma
      Ab, both early and late IL-2 administration exacerbated CIA. Thus, IL-2 can have
      two opposite effects on autoimmune arthritis, a direct stimulatory effect and an
      indirect suppressive effect that is mediated by IFN-gamma.

PMID- 10903765
TI  - Airway remodeling is absent in CCR1-/- mice during chronic fungal allergic airway
      disease.
AB  - Asthmatic-like reactions characterized by elevated IgE, Th2 cytokines, C-C
      chemokines, eosinophilic inflammation, and persistent airway hyperresponsiveness
      follow pulmonary exposure to the spores or conidia from Aspergillus fumigatus
      fungus in sensitized individuals. In addition to these features, subepithelial
      fibrosis and goblet cell hyperplasia characterizes fungal-induced allergic airway
      disease in mice. Because lung concentrations of macrophage inflammatory protein
      1alpha and RANTES were significantly elevated after A. fumigatus-sensitized mice
      received an intrapulmonary challenge with A. fumigatus spores or conidia, the
      present study addressed the role of their receptor, C-C chemokine receptor 1
      (CCR1), in this model. A. fumigatus-sensitized CCR1 wild-type (+/+) and CCR1
      knockout (-/-) mice exhibited similar increases in serum IgE and
      polymorphonuclear leukocyte numbers in the bronchoalveolar lavage. Airway
      hyperresponsiveness was prominent in both groups of mice at 30 days after an
      intrapulmonary challenge with A. fumigatus spores or conidia. However, whole lung
      levels of IFN-gamma were significantly higher whereas IL-4, IL-13, and Th2
      inducible chemokines such as C10, eotaxin, and macrophage-derived chemokine were
      significantly lower in whole lung samples from CCR1-/- mice compared with CCR1+/+
      mice at 30 days after the conidia challenge. Likewise, significantly fewer goblet
      cells and less subepithelial fibrosis were observed around large airways in CCR1
      /- mice at the same time after the conidia challenge. Thus, these findings
      demonstrate that CCR1 is a major contributor to the airway remodeling responses
      that arise from A. fumigatus-induced allergic airway disease.

PMID- 10903766
TI  - Annexin 1 binds to U937 monocytic cells and inhibits their adhesion to
      microvascular endothelium: involvement of the alpha 4 beta 1 integrin.
AB  - Annexin 1 (ANX1), a calcium-binding protein, participates in the regulation of
      early inflammatory responses. Whereas some of its effects depend on intracellular
      interactions, a growing number of observations indicate that ANX1 may also act
      via autocrine/paracrine functions following externalization to the outer side of
      the plasma membrane. We studied the effects of ANX1 on leukocyte adhesion to
      endothelial cells using as a model system the monocytic cell line U937 and human
      bone marrow microvascular endothelial cells. Exogenous rANX1, as well as
      endogenous ANX1 externalized by U937 differentiated in vitro, inhibited monocyte
      firm adhesion to vascular endothelium. Both binding of ANX1 to U937 cells and
      ANX1-mediated inhibition of cell adhesion involved the short N-terminal domain of
      the ANX1 molecule. Under experimental conditions in which ANX1 inhibited U937
      adhesion to human bone marrow microvascular endothelial cells, this protein
      specifically colocalized with the alpha 4 integrin, and a direct interaction
      between ANX1 and the alpha 4 integrin could be documented by immunoprecipitation
      experiments. Moreover, ANX1 competed with the endothelial integrin
      counterreceptor, VCAM-1, for binding to alpha 4 integrin. These results indicate
      that ANX1 plays an important physiological role in modulating monocyte firm
      adhesion to the endothelium.

PMID- 10903767
TI  - Nitric oxide synthase/COX cross-talk: nitric oxide activates COX-1 but inhibits
      COX-2-derived prostaglandin production.
AB  - It is recognized that there is molecular cross-talk between the inflammatory
      mediators NO and PGs that may regulate tissue homeostasis and contribute to
      pathophysiological processes. However, the literature is divided with respect to
      whether NO activates or inhibits PG production. In this study, we sought to
      determine whether conflicting observations could be accounted for by divergent
      effects of NO on the two cyclooxygenase (COX) isoforms. Exposure of resting
      macrophages to NO (30 microM) enhanced PGE2 release by 4. 5-fold. This
      enhancement was inhibited by indomethacin but not by the COX-2 selective
      inhibitor NS398. To separate the activation of phospholipase A2 and COX, we
      performed experiments using fibroblasts derived from COX-1-deficient or COX-2
      deficient mice. These cells exhibit increased basal PG production, which is due
      to a constitutively stimulated cytosolic phospholipase A2 and enhanced basal
      expression of the remaining COX isozyme. The exposure of COX- 2-deficient cells
      to exogenous NO (10 microM) resulted in a 2.4-fold increase of PGE2 release above
      controls. Further studies indicated that NO stimulated PGE2 release in COX-2
      deficient cells, without altering COX-1 mRNA or protein expression. In contrast,
      NO inhibited COX-2-derived PGE2 production in both LPS-stimulated macrophages and
      COX-1 knockout cells. This inhibition was associated with both decreased
      expression and nitration of COX-2. Thus, these studies demonstrate divergent
      effects of NO on the COX isoforms. The regulation of PGE production by NO is
      therefore complex and will depend on the local environment in which these
      pleiotropic mediators are produced.

PMID- 10903768
TI  - Early local generation of C5a initiates the elicitation of contact sensitivity by
      leading to early T cell recruitment.
AB  - We have shown previously that an early complement C5-dependent cascade is
      required to recruit T cells to elicit 24-h contact sensitivity (CS) responses. In
      this paper, we have characterized molecular events of this early required cascade
      by biochemically analyzing extracts of mouse ears undergoing elicitation of CS.
      Chemotactic activity was found after local Ag challenge, in CS ear extracts early
      (by 1 h), in CS ear extracts late (through 24 h), in previously immunized mice,
      but not in ears of vehicle-immunized or non-immune-challenged mice. The early
      chemotactic activity at 2 h was likely caused by C5a, because it was neutralized
      in vitro by anti-C5a Ab, was inactive on C5aR-deficient (C5aR-/-) macrophages,
      and was absent in C5-deficient mice. The activity was present in T cell-deficient
      mice, but elaboration was Ag-specific. This T cell-independent, Ag-specific
      elaboration of C5a early in CS ear responses likely led to T cell recruitment,
      because subsequent local IFN-gamma mRNA and protein expression, as markers of T
      cell arrival and activation, began by 4 h after Ag challenge. In contrast to
      early C5a chemotactic activity, late chemotactic activity 24 h after Ag challenge
      was unaffected by anti-C5, was active on C5aR-/- macrophages, was T cell
      dependent, and by ELISA appeared largely due to chemokines (macrophage
      inflammatory protein-1alpha and -1beta, IFN-gamma-inducible protein-10, and
      monocyte chemoattractant protein-1). Importantly, early generation of C5a was
      required for T cell recruitment because C5aR-/- mice had absent 24-h CS. Taken
      together, these findings indicate an important linkage of C5a as a component of
      early activated innate immunity that is required for later elicitation of
      acquired T cell immunity, probably by facilitating the initial recruitment of T
      cells into the Ag-challenged local site in CS responses.

PMID- 10903769
TI  - Phenotypic and functional maturation of dendritic cells mediated by heparan
      sulfate.
AB  - Primary immune responses are thought to be induced by dendritic cells. To promote
      such responses, dendritic cells must be activated by exogenous agonists, such as
      LPS, or by products of activated leukocytes, such as TNF-alpha and IL-1. How
      dendritic cells might be activated in the absence of exogenous stimuli, or
      without the immediate presence of activated leukocytes, as might occur in
      immunity to tumor cells or transplants, is unknown. We postulated that heparan
      sulfate, an acidic, biologically active polysaccharide associated with cell
      membranes and extracellular matrices, which is rapidly released under conditions
      of inflammation and tissue damage, might provide such a stimulus. Incubation of
      immature murine dendritic cells with heparan sulfate induced phenotypic
      maturation evidenced by up-regulation of I-A, CD40, CD54 (ICAM-1), CD80 (B7-1),
      and CD86 (B7-2). Dendritic cells exposed to heparan sulfate exhibited a markedly
      lowered rate of Ag uptake and increased allostimulatory capacity. Stimulation of
      dendritic cells with heparan sulfate induced release of TNF-alpha, IL-1beta, and
      IL-6, although the maturation of dendritic cells was independent of these
      cytokines. These results suggest that soluble heparan sulfate chains, as products
      of the degradation of heparan sulfate proteoglycan, might induce maturation of
      dendritic cells without exogenous stimuli, thus contributing to the generation
      and maintenance of primary immune responses.

PMID- 10903770
TI  - Differential regulation of prostaglandin E2 and thromboxane A2 production in
      human monocytes: implications for the use of cyclooxygenase inhibitors.
AB  - There is an autocrine relationship between eicosanoid and cytokine synthesis,
      with the ratio of prostaglandin E2 (PGE2)/thromboxane A2 (TXA2) being one of the
      determinants of the level of cytokine synthesis. In monocytes, cyclooxygenase
      type 1 (COX-1) activity appears to favor TXA2 production and COX-2 activity
      appears to favor PGE2 production. This has led to speculation regarding possible
      linkage of COX isozymes with PGE and TXA synthase. We have studied the kinetics
      of PGE2 and TXA2 synthesis under conditions that rely on COX-1 or -2 activity.
      With small amounts of endogenously generated prostaglandin H2 (PGH2), TXA2
      synthesis was greater than PGE2. With greater amounts of endogenously generated
      PGH2, PGE2 synthesis was greater than TXA2. Also, TXA synthase was saturated at
      lower substrate concentrations than PGE synthase. This pattern was observed
      irrespective of whether PGH2 was produced by COX-1 or COX-2 or whether it was
      added directly. Furthermore, the inhibition of eicosanoid production by the
      action of nonsteroidal anti-inflammatory drugs or by the prevention of COX-2
      induction with the p38 mitogen-activated protein kinase inhibitor SKF86002 was
      greater for PGE2 than for TXA2. It is proposed that different kinetics of PGE
      synthase and TXA synthase account for the patterns of production of these
      eicosanoids in monocytes under a variety of experimental conditions. These
      properties provide an alternative explanation to notional linkage or
      compartmentalization of COX-1 or -2 with the respective terminal synthases and
      that therapeutically induced changes in eicosanoid ratios toward predominance of
      TXA2 may have unwanted effects in long-term anti-inflammatory and anti-arthritic
      therapy.

PMID- 10903771
TI  - Role of Stat3 in lipopolysaccharide-induced IL-10 gene expression.
AB  - IL-10 is a unique cytokine because it is anti-inflammatory and immunosuppressive.
      IL-10 is regulated at the level of transcription, but the critical motifs and the
      relevant transcription factors controlling this gene have remained elusive to
      date. We now report that a sequence at -120 bp in the human IL-10 promoter binds
      Stat3 but no other Stat proteins. Mutation of this motif abrogates LPS-induced
      trans-activation. Overexpression of dominant negative Stat3 suppresses promoter
      activity, while wild-type Stat3 leads to an enhancement of this activity. Our
      results show that Stat3, by binding to a single motif in the IL-10 promoter, is
      controlling expression of the human IL-10 gene.

PMID- 10903772
TI  - Regulation of expression of granulocyte-macrophage colony-stimulating factor in
      human bronchial epithelial cells: roles of protein kinase C and mitogen-activated
      protein kinases.
AB  - GM-CSF has a major role in the immune and inflammatory milieu of the airway.
      Airway epithelial cells (AEC) are among the first targets of environmental
      stimuli and local cytokines, in response to which they can produce GM-CSF. The
      regulation of GM-CSF is only minimally understood in AEC. We hypothesized that GM
      CSF expression in AEC would result from activation of protein kinase C (PKC) and
      subsequent activation of the extracellular signal-regulated kinase (MAPKerk1/2)
      pathway, so we investigated signal transduction pathways in human primary culture
      bronchial epithelial cells (HBECs). TNF-alpha, IL-1beta, and PMA induced the
      release of GM-CSF in HBECs. The robust response to PMA was not detected in SV40
      adenovirus-transformed normal human bronchial epithelial cells (BEAS-2B). PMA and
      TNF-alpha stimulation of GM-CSF required activation of PKC (inhibition by
      staurosporine and bisindolylmaleimide I). GM-CSF expression was up-regulated by a
      nonphorbol PKC activator, but not by an inactive PMA analogue. PMA-induced GM-CSF
      production in HBECs did not require a Ca2+ ionophore and was not inhibited by
      cyclosporin A. Activation of MAPKerk1/2 via PKC was associated with and was
      required for GM-CSF production induced by PMA and TNF-alpha. The data demonstrate
      regulation of GM-CSF in HBECs by PKC pathways converging on the MAPKerk1/2
      pathway and further define cell-specific regulation critical for local airway
      responses.

PMID- 10903773
TI  - Immune complexes present in the sera of autoimmune mice activate rheumatoid
      factor B cells.
AB  - The fate of an autoreactive B cell is determined in part by the nature of the
      interaction of the B cell receptor with its autoantigen. In the lpr model of
      systemic autoimmunity, as well as in certain human diseases, autoreactive B cells
      expressing rheumatoid factor (RF) binding activity are prominent. A murine B cell
      transgenic model in which the B cell receptor is a RF that recognizes IgG2a of
      the j allotype (IgG2aj), but not the b allotype, was used in this study to
      investigate how the form of the autoantigen influences its ability to activate B
      cells. We found that sera from autoimmune mice, but not from nonautoimmune mice,
      were able to induce the proliferation of these RF+ B cells but did not stimulate
      B cells from RF- littermate controls. The stimulatory factor in serum was found
      to be IgG2aj, but the IgG2aj was stimulatory only when in the form of immune
      complexes. Monomeric IgG2aj failed to stimulate. Immune complexes containing
      lupus-associated nuclear and cytoplasmic autoantigens were particularly potent B
      cell activators in this system. Appropriate manipulation of such
      autoantibody/autoantigen complexes may eventually provide a means for therapeutic
      intervention in patients with certain systemic autoimmune disorders.

PMID- 10903774
TI  - Adoptively transferred gamma delta T cells indirectly regulate murine graft
      versus-host reactivity following donor leukocyte infusion therapy in mice.
AB  - The purpose of this study was to determine whether gamma delta T cells were able
      to regulate graft-vs-host (GVH) reactivity mediated by alpha beta T cells in
      murine recipients transplanted with MHC-mismatched marrow grafts. Studies were
      conducted using ex vivo-activated gamma delta T cells because this was a more
      clinically relevant strategy, and these cells have been shown to be capable of
      facilitating alloengraftment without causing GVH disease (GVHD). Coadministration
      of activated gamma delta T cells and naive alpha beta T cells at the time of bone
      marrow transplantation (BMT) significantly exacerbated GVHD when compared with
      naive alpha beta T cells alone. In contrast, when the administration of naive
      alpha beta T cells was delayed for 2 wk post-BMT, survival was significantly
      enhanced in mice transplanted with BM plus activated gamma delta T cells vs those
      given marrow cells alone. Mitigation of GVHD by activated gamma delta T cells
      occurred only at high doses (150 x 106) and was a unique property of gamma delta
      T cells, as activated alpha beta T cells were incapable of ameliorating the
      subsequent development of GVHD. Protection from GVHD was not due to the direct
      inhibition of naive alpha beta T cells by gamma delta T cells. Rather, gamma
      delta T cells mediated this effect indirectly through donor BM-derived alpha beta
      T cells that acted as the proximate regulatory population responsible for the
      decrease in GVH reactivity. Collectively, these data demonstrate that activated
      gamma delta T cells are capable of modulating the ability of MHC-incompatible
      nontolerant alpha beta T cells to cause GVHD after allogeneic BMT.

PMID- 10903775
TI  - Quantification of self-recognition in multiple sclerosis by single-cell analysis
      of cytokine production.
AB  - Identifying and quantifying autoaggressive responses in multiple sclerosis (MS)
      has been difficult in the past due to the low frequency of autoantigen-specific T
      cells, the high number of putative determinants on the autoantigens, and the
      different cytokine signatures of the autoreactive T cells. We used single-cell
      resolution enzyme-linked immunospot (ELISPOT) assays to study, directly ex vivo,
      proteolipid protein (PLP)-specific memory cell reactivity from MS patients and
      controls. Overlapping 9-aa-long peptides, spanning the entire PLP molecule in
      single amino acid steps, were used to determine the frequency and fine
      specificity of PLP-specific lymphocytes as measured by their IFN-gamma and IL-5
      production. MS patients (n = 22) responded to 4 times as many PLP peptides as did
      healthy controls (n = 22). The epitopes recognized in individual patients, up to
      22 peptides, were scattered throughout the PLP molecule, showing considerable
      heterogeneity among MS patients. Frequency measurements showed that the number of
      PLP peptide-specific IFN-gamma-producing cells averaged 11 times higher in MS
      patients than in controls. PLP peptide-induced IL-5-producing T cells occurred in
      very low frequencies in both MS patients and controls. This first comprehensive
      assessment of the anti-PLP-Th1/Th2 response in MS shows a greatly increased Th1
      effector cell mass in MS patients. Moreover, the highly IFN-gamma-polarized, IL-5
      negative cytokine profile of the PLP-reactive T cells suggests that these cells
      are committed Th1 cells. The essential absence of uncommitted Th0 cells producing
      both cytokines may explain why therapeutic strategies that aim at the induction
      of immune deviation show little efficacy in the established disease.

PMID- 10903776
TI  - The effect of a T cell-specific NF-kappa B inhibitor on in vitro cytokine
      production and collagen-induced arthritis.
AB  - NF-kappa B plays a key role in the production of cytokines in inflammatory
      diseases. The effects of a novel T cell-specific NF-kappa B inhibitor, SP100030,
      were evaluated in cultured Jurkat cells and in murine collagen-induced arthritis
      (CIA). Chemical libraries were screened for NF-kappa B-inhibitory activity.
      SP100030, a compound identified in this process, inhibited NF-kappa B activation
      in PMA/PHA-activated Jurkat cells by EMSA at a concentration of 1 microM. Jurkat
      cells and the monocytic cell line THP-1 were transfected with an NF-kappa B
      promotor/luciferase construct and activated. SP100030 inhibited luciferase
      production in the Jurkat cells (IC50 = 30 nM). ELISA and RT-PCR confirmed that IL
      2, IL-8, and TNF-alpha production by activated Jurkat and other T cell lines were
      inhibited by SP100030. However, cytokine expression was not blocked by the
      compound in THP-1 cells, fibroblasts, endothelial cells, or epithelial cells.
      Subsequently, DBA/1J mice were immunized with type II collagen. Treatment with
      SP100030 (10 mg/kg/day i.p. beginning on day 21) significantly decreased
      arthritis severity from onset of clinical signs to the end of the study on day 34
      (arthritis score, 5.6 +/- 1.7 for SP100030 and 9.8 +/- 1.5 for control; p <
      0.001). Histologic evaluation demonstrated a trend toward improvement in SP100030
      treated animals. EMSA of arthritic mouse ankles in CIA showed that synovial NF
      kappa B binding was suppressed in the SP100030-treated mice. SP100030 inhibits NF
      kappa B activation in T cells, resulting in reduced NF-kappa B-regulated gene
      expression and decreased CIA. Its selectivity for T cells could provide potent
      immunosuppression with less toxicity than other NF-kappa B inhibitors.

PMID- 10903777
TI  - Alpha-glycosylceramides enhance the antitumor cytotoxicity of hepatic lymphocytes
      obtained from cancer patients by activating CD3-CD56+ NK cells in vitro.
AB  - Alpha-glycosylceramides, such as alpha-galactosylceramide and alpha
      glucosylceramide, induce antitumor immunity in various murine cancer models. In
      the murine hepatic metastasis model, V alpha 14 TCR+NK1.1+ T cells, which
      accumulate preferentially in the liver, are considered to play a key role in the
      induction of antitumor immunity by alpha-glycosylceramides. We recently reported
      that V alpha 24 TCR+ NKT cells, the human homologues of murine V alpha 14
      TCR+NK1.1+ cells, are rarely seen among freshly isolated human hepatic
      lymphocytes. Therefore, it is important to examine whether alpha
      glycosylceramides also enhance the antitumor cytotoxicity of human hepatic
      lymphocytes, as they have been shown to do in murine systems, to determine the
      usefulness of alpha-glycosylceramides in cancer immunotherapy in humans. Here, we
      show that alpha-glycosylceramides greatly enhance the cytotoxicity of human
      hepatic lymphocytes obtained from cancer patients against the tumor cell lines,
      K562 and Colo201, in vitro. The direct effector cells of the elicited
      cytotoxicity were CD3-CD56+ NK cells. Even though V alpha 24 TCR+NKT cells
      proliferated remarkably in response to alpha-glycosylceramides, they did not
      contribute directly to the cytotoxicity. Our observations strongly suggest the
      potential usefulness of alpha-glycosylceramides for immunotherapy of liver cancer
      in humans based on their ability to activate CD3-CD56+ NK cells in the liver.

PMID- 10903778
TI  - Genetic control of glycoprotein 70 autoantigen production and its influence on
      immune complex levels and nephritis in murine lupus.
AB  - The F1 hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice
      spontaneously develop an autoimmune disease that serves as a model for human
      systemic lupus erythematosus. Autoimmunity in (NZB x NZW)F1 mice includes the
      production of autoantibodies to the endogenous retroviral envelope glycoprotein,
      gp70, and gp70-anti-gp70 immune complexes (gp70 IC) have been implicated in the
      development of lupus nephritis in these animals. We used backcross and intercross
      combinations of C57BL/6 (B6; low gp70 levels) and NZB mice (high gp70 levels) to
      examine the contribution of serum gp70 Ag levels to the development of gp70 IC
      and nephritis. Analysis of (B6.H2z x NZB)F1 x NZB backcross mice and (NZB x B6)F2
      mice showed a much stronger association of gp70 IC with kidney disease compared
      with IgG anti-chromatin autoantibodies in both populations of mice. Serum levels
      of gp70 correlated with production of gp70 IC in mice producing autoantibodies,
      although the overall effect on nephritis appeared to be small. Genetic mapping
      revealed three NZB-derived regions on chromosomes 2, 4, and 13 that were strongly
      linked with increased gp70 levels, and together, accounted for over 80% of the
      variance for this trait. However, additional linkage analyses of these crosses
      showed that loci controlling autoantibody production rather than gp70 levels were
      most important in the development of nephritogenic immune complexes. Together,
      these studies characterize a set of lupus-susceptibility loci distinct from those
      that control autoantibody production and provide new insight into the components
      involved in the strong association of gp70 IC with murine lupus nephritis.

PMID- 10903779
TI  - Linkage analysis of systemic lupus erythematosus induced in diabetes-prone
      nonobese diabetic mice by Mycobacterium bovis.
AB  - Systemic lupus erythematosus induced by Mycobacterium bovis in diabetes-prone
      nonobese diabetic mice was mapped in a backcross to the BALB/c strain. The
      subphenotypes-hemolytic anemia, antinuclear autoantibodies, and glomerular immune
      complex deposition-did not cosegregate, and linkage analysis for each trait was
      performed independently. Hemolytic anemia mapped to two loci: Bah1 at the MHC on
      chromosome 17 and Bah2 on distal chromosome 16. Antinuclear autoantibodies mapped
      to three loci: Bana1 at the MHC on chromosome 17, Bana2 on chromosome 10, and
      Bana3 on distal chromosome 1. Glomerular immune complex deposition did not show
      significant linkage to any genomic region. Mapping of autoantibodies (Coombs' or
      antinuclear autoantibodies) identified two loci: Babs1 at the MHC and Babs2 on
      distal chromosome 1. It has previously been reported that genes conferring
      susceptibility to different autoimmune diseases map nonrandomly to defined
      regions of the genome. One possible explanation for this clustering is that some
      alleles at loci within these regions confer susceptibility to multiple autoimmune
      diseases-the "common gene" hypothesis. With the exception of the H2, this study
      failed to provide direct support for the common gene hypothesis, because the loci
      identified as conferring susceptibility to systemic lupus erythematosus did not
      colocalize with those previously implicated in diabetes. However, three of the
      four regions identified had been previously implicated in other autoimmune
      diseases.

PMID- 10903780
TI  - CD40 ligand trimer and IL-12 enhance peripheral blood mononuclear cells and CD4+
      T cell proliferation and production of IFN-gamma in response to p24 antigen in
      HIV-infected individuals: potential contribution of anergy to HIV-specific
      unresponsiveness.
AB  - It has been suggested that CD4+ T cell proliferative responses to HIV p24 Ag may
      be important in the control of HIV infection. However, these responses are
      minimal or absent in many HIV-infected individuals. Furthermore, while in vitro
      and in vivo responses to non-HIV recall Ags improve upon administration of highly
      active antiretroviral therapy, there does not appear to be a commensurate
      enhancement of HIV-specific immune responses. It is possible that CD4+ p24
      specific T cells are deleted early in the course of infection. However, it is
      also possible that a discrete unresponsiveness, or anergy, contributes to the
      lack of proliferation to p24. To evaluate the possible contribution of
      unresponsiveness to the lack of CD4+ T cell proliferation to p24 in HIV-infected
      individuals, we attempted to overcome unresponsiveness. CD40 ligand trimer
      (CD40LT) and IL-12 significantly increased PBMC and CD4+ T cell proliferative
      responses to p24 Ag in HIV-infected, but not uninfected, individuals. No increase
      in proliferative response to CMV Ag was observed. CD40LT exerted its effect
      through B7-CD28-dependent and IL-12- and IL-15-independent mechanisms. Finally,
      the increase in proliferation with CD40LT and IL-12 was associated with an
      augmented production of IFN-gamma in most, but not all, individuals. These data
      suggest the possible contribution of HIV-specific unresponsiveness to the lack of
      CD4+ T cell proliferation to p24 Ag in HIV-infected individuals and that clonal
      deletion alone does not explain this phenomenon. They also indicate the potential
      for CD40LT and IL-12 as immune-based therapies for HIV infection.

PMID- 10903781
TI  - Dynamics of HIV-specific CD8+ T lymphocytes with changes in viral load.The RESTIM
      and COMET Study Groups.
AB  - The influence of HIV burden variations on the frequencies of Ag-specific CD8+ T
      cell responses was evaluated before and during highly active antiretroviral
      therapy by analyzing the number, diversity, and function of these cells. The
      frequencies of HLA-A2-restricted CD8+ PBL binding HLA-A2/HIV-epitope tetramers or
      producing IFN-gamma were below 1%. A panel of 16 CTL epitopes covering 15 HLA
      class I molecules in 14 patients allowed us to test 3.8 epitopes/patient and to
      detect 2.2 +/- 1.8 HIV epitope-specific CD8+ subsets per patient with a median
      frequency of 0.24% (0.11-4. 79%). During the first month of treatment, viral load
      rapidly decreased and frequencies of HIV-specific CD8 PBL tripled, eight new HIV
      specificities appeared of 11 undetectable at entry, while CMV-specific CD8+ PBL
      also appeared. With efficient HIV load control, all HIV specificities decayed
      involving a reduction of the CD8+CD27+CD11ahigh HIV-specific effector subset.
      Virus rebounds triggered by scheduled drug interruptions or transient therapeutic
      failures induced four patterns of epitope-specific CD8+ lymphocyte dynamics,
      i.e., peaks or disappearance of preexisting specificities, emergence of new
      specificities, or lack of changes. The HIV load rebounds mobilized both
      effector/memory HIV- and CMV-specific CD8+ lymphocytes. Therefore, frequencies of
      virus-specific CD8 T cells appear to be positively correlated to HIV production
      in most cases during highly active antiretroviral therapy, but an inverse
      correlation can also be observed with rapid virus changes that might involve
      redistribution, sequestration, or expansion of these Ag-specific CD8 T cells.
      Future strategies of therapeutic interruptions should take into account these
      various HIV-specific cell dynamics during HIV rebounds.

PMID- 10903783
TI  - Ce n'est pas encore du cancer, mais c'est deja de la therapie genique

PMID- 10903782
TI  - Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic
      cells induce antitumor immunity.
AB  - Human ovarian carcinomas express the CA-125, HER2/neu, and MUC1 tumor-associated
      Ags as potential targets for the induction of active specific immunotherapy. In
      the present studies, human ovarian cancer cells were fused to human dendritic
      cells (DC) as an alternative strategy to induce immunity against known and
      unidentified tumor Ags. Fusions of ovarian cancer cells to autologous DC resulted
      in the formation of heterokaryons that express the CA-125 Ag and DC-derived
      costimulatory and adhesion molecules. Similar findings were obtained with ovarian
      cancer cells fused to allogeneic DC. The fusion cells were functional in
      stimulating the proliferation of autologous T cells. The results also demonstrate
      that fusions of ovarian cancer cells to autologous or allogeneic DC induce
      cytolytic T cell activity and lysis of autologous tumor cells by a MHC class I
      restricted mechanism. These findings demonstrate that fusions of ovarian
      carcinoma cells and DC activate T cell responses against autologous tumor and
      that the fusions are functional when generated with either autologous or
      allogeneic DC.

PMID- 10903784
TI  - [Fibers, intestinal polyps and cancer: without effect but the ink continuous to
      flow].

PMID- 10903785
TI  - [Loss of heterozygosity as a tool in the evaluation of cancer risk in
      premalignant lesions of the head and neck].

PMID- 10903786
TI  - [An angiogenesis inhibitor: TNP-470].

PMID- 10903787
TI  - [Update on gastroenterology].
AB  - In the field of mass detection of colorectal cancer by Hemoccul test, the results
      of the Burgundy study confirm the two european studies previously published and
      encourage to extend this training to the whole country. In oncogenetic field, a
      recent publication suggest some different clinical criteria that Amsterdam
      criteria to define a Lynch syndrome. When genetic markers are performed in a
      population selected according to these type I criteria, HNPCC mutation could be
      detected in 28% of cases. In colorectal cancer surgery, the debate remains open
      on the place of coeliosurgery. A recent published series of 135 colon cancers
      operated by coeliosurgery do not show any recurrence on trocar orifices. A US
      study has confirmed the prognostic value of the number of lymph nodes analyzed
      after resection of colorectal cancer. In adjuvant treatment of stage II colon
      cancer, two contradictory publications have been reported in the Journal of
      Clinical Oncology. However, the results of the Impact B2 Group are more
      consistent and support the fact that chemotherapy cannot be recommended as a
      standard treatment in state II colon cancer. The actualities in the liver
      metastases focused on the new local destruction technics that are cryosurgery and
      radiofrequency. Concerning the chemotherapy of metastatic colorectal cancer,
      important results have been published in second line therapy showing the
      superiority of Campto compared to best supportive care or 5FU based chemotherapy
      both in term of overall survival and quality of life. In first line chemotherapy,
      the superiority of bi-therapies (LV5FU2 and oxaliplatin or LV5FU2 and irinotecan)
      has been confirmed compared to LV5FU2 alone. A recent publication showed that
      patients older than 70 years tolerate chemotherapy for colorectal cancer as well
      as younger patients with the same efficacy. In esophagus carcinoma, the most
      important study didn't show any efficacy of neoadjuvant chemotherapy by 5FU
      cisplatin in operable adenocarcinoma of squamous carcinoma of esophagus. The
      final results of dutch's study in node dissection for gastric cancer do not find
      any benefit in overall survival comparing D2 versus D1 dissection with a
      substantial increase in morbidity and mortality in the D2 arm, specially when
      splenopancreatectomy was performed. Finally, an important study has confirmed the
      value of per echoendoscopy biopsies for the diagnosis of positive lymph nodes and
      pancreatic tumors.

PMID- 10903788
TI  - [Knowledge and management of psychological side effects of chemotherapies].
AB  - This review on psychological consequences of chemotherapies presents the research
      directions developed during the last two years: the first direction is a
      descriptive one and identifies the prevalence of psychological syndromes
      associated with these treatments. Besides psychological distress such as anxiety
      and depression, often underestimated in medical practice, some secondary
      cognitive deficiencies ought to be considered. It is also emphasized that the
      point of view of patients should be taken into account since their own assessment
      of the side effects is often discrepant with those of their medical providers.
      The second orientation developed here is the evaluation of actions aimed at
      controlling and alleviating the psychological consequences of these treatments by
      different protocols of information and psychotherapy. Good quality research is
      necessary in psycho-oncology in France and should be co-ordinated with clinical
      practice in psychology the offer of which is still too limited in our present
      health care system.

PMID- 10903789
TI  - [Standards, Options and Recommendations (SOR) for endocrine therapy in patients
      with non metastatic breast cancer. FNCLCC].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in
      1993, is a collaboration between the Federation of the French Cancer Centres
      (FNCLCC), the 20 French Cancer Centres and specialists from French Public
      Universities, General Hospitals and Private Clinics. The main objective is the
      development of clinical practice guidelines to improve the quality of health care
      and outcome for cancer patients. The methodology is based on literature
      systematic review and critical appraisal by a multidisciplinary group of experts,
      with feedback from specialists in cancer care delivery. OBJECTIVES: To develop
      clinical practice guidelines according to the definitions of Standards, Options
      and Recommendations for endocrine therapy in patients with non metastatic breast
      cancer. METHODS: Data have been identified by literature search using Medline,
      Embase, Cancerlit and Cochrane databases - until july 1999 - and the personal
      reference lists of the expert group. Once the guidelines were defined, the
      document was submitted for review to 125 independent reviewers. RESULTS: The main
      recommendations for the endocrine therapy of patients with non metastatic breast
      cancer are: 1) Endocrine therapy modalities depend on menopausal status or age of
      women: ovarian suppression for premenopausal women, antiestrogen drug therapy for
      postmenopausal women (standard). 2) Tamoxifen (20 mg/d - 5 years) is beneficial
      to women with positive estrogen receptor tumor (standard, level of evidence A).
      There is no indication of tamoxifen treatment for women with negative estrogen
      receptor tumor (standard, level of evidence A). 3) For postmenopausal women with
      positive estrogen receptor tumor, tamoxifen is the standard adjuvant treatment
      (level of evidence A). For postmenopausal women with negative estrogen receptor,
      adjuvant chemotherapy has to be considered (option, level of evidence A). No
      adjuvant treatment has to be considered for women with poor health condition
      (option). 4) For premenopausal women with estrogen receptor tumor, results of
      clinical trials of chemotherapy versus endocrine therapy, suggest a benefit for
      endocrine therapy. However, there is no sufficient evidence to consider endocrine
      therapy alone as a standard adjuvant treatment. 5) For premenopausal women,
      chemotherapy + ovarian suppression or chemotherapy + tamoxifen are not better
      than chemotherapy alone (level of evidence A). 6) For postmenopausal women,
      administration of chemotherapy plus adjuvant tamoxifen versus the same tamoxifen
      alone, is of additional benefit in reducing recurrences but not in prolonging
      overall survival (standard, level of evidence A). 7) Balance of known benefits
      (delay to recurrence and death) and risks (side-effects of therapy) for adjuvant
      chemoendocrine therapy has to be taken into consideration before decision making.
      Chemoendocrine therapy can be indicated for women at high risk of developing
      metastatic disease (recommendation, experts agreement).

PMID- 10903790
TI  - [Improvement in the control of chemotherapy induced emesis with ondansetron,
      methylprednisolone and lorazepam combination in patients treated by a moderate
      emetic treatment and uncontrolled by a previous antiemetic combination].
AB  - The objective of this double blind parallel-group multicentre study was to
      compare the efficacy and safety of the combination ondansetron +
      methylprednisolone + lorazepam (O + M + L) in the prevention of emesis induced by
      chemotherapy with cyclophosphamide or adriamycin . This tritherapy was compared
      to a bitherapy O + M. Patients included were suffering from severe haemopathy or
      breast cancer. They had to have an incomplete response to a previous antiemetic
      association of 5HT3 serotoninergic receptor antagonist and corticoid. One hundred
      and thirty-five adult patients were included and were randomised to receive : O +
      M + L or O + M for 3 days. The emesis control during the 3 days of treatment (no
      emetic episode during the complete course) was significantly superior in the
      group O + M + L than in the group O + M (69% versus 46%, p = 0. 042); nausea
      control on the worst day of the cure was significantly superior in the group O +
      M + L than in the group O + M (p = 0.04) with 76% of patients in the group O + M
      + L having complete or major nausea control compared to 51% in the group O + M.
      The stability of quality of life during the days following chemotherapy measured
      by one questionnaire, including two scales, one cancer specific (FLIC) and one
      emesis specific (FLIE), appeared significantly better in group O + M + L (p =
      0.04 and p = 0.019). Safety of both antiemetic regimens was good and similar
      between the two treatment groups. This trial shows that the adjunction of
      lorazepam to ondansetron and corticoid in combination increases the antiemetic
      control for patients with an incomplete response to a previous regimen containing
      a 5HT3 serotoninergic receptor antagonist and a corticosteroid in the prevention
      of chemotherapy-induced emesis.

PMID- 10903791
TI  - [The consensus conference on the treatment of in situ ductal carcinoma of the
      breast, April 22-25, 1999].

PMID- 10903792
TI  - [Annual meeting of the American Association for Cancer Research].

PMID- 10903794
TI  - Can interleukin-10 be used as a true immunoregulatory cytokine?
AB  - Interleukin-10 (IL-10) is a cytokine that is currently regarded as a potential
      therapy for inflammatory diseases involving T helper 1-type responses because of
      its ability to downregulate several major functions of Th1 cells and macrophages.
      There are also evidence that IL-10 could be useful in controlling Th2-mediated
      inflammatory processes. However IL-10 has also immunostimulatory properties
      especially on B-cells and activated CD8+ T cells. These pleiotropic effects may
      explain the discrepancy observed after IL-10 treatment in different in vivo
      experimental models. We have recently shown that IL-10 induces the
      differentiation of a subset of regulatory CD4+ T cells (Tr1). In different in
      vivo models, these cells were shown to inhibit Th1 and Th2-type inflammatory
      responses through the secretion of IL-10. These Tr1 cells may thus be used in
      specific cellular therapy in order to deliver IL-10 precisely at the site of
      inflammation.

PMID- 10903793
TI  - Positional cloning of Lps, and the general role of toll-like receptors in the
      innate immune response.
AB  - In mice (and by inference, in all mammals), a single pathway exists to serve
      lipopolysaccharide (LPS) signal transduction, and as such, allelic mutations at a
      single locus entirely abolish responses to LPS in C3H/HeJ and C57BL/10ScCr mice.
      Positional cloning of this locus, known as Lps, revealed that mutations of the
      Toll-like receptor 4 gene (Tlr4) are responsible for endotoxin resistance. A
      quick succession of studies have shown Tlr4 to be the critical transmembrane
      component of the LPS signal transduction complex. As LPS sensing by Tlr4 depends
      on physical contact between the two molecules, Tlr4 is a direct interface with
      the microbial world. Eight other molecules with strong similarity to Tlr4 are
      presently known in mammals, and taking Tlr4 as a model, all may be guessed to
      participate in the early detection of invasive pathogens. Acting together, the
      Toll-like receptors may be assumed to present macrophages with a comprehensive
      "picture" of the micobial world, and thus comprise the principal sensing
      molecules utilized by cells of the innate immune system.

PMID- 10903795
TI  - Somatostatin and somatostatin receptors in the immune system: a review.
AB  - Communication and reciprocal regulation between the nervous, endocrine and immune
      systems are essential for the stability of the organism. Among others, cytokines,
      hormones and neuropeptides have been identified as signalling molecules mediating
      the communication between the three systems. This review focuses on the role of
      the neuropeptide somatostatin as an intersystem signalling molecule, with
      emphasis on the immune system. Somatostatin down-modulates a number of immune
      functions, among others lymphocyte proliferation, immunoglobulin production and
      the release of proinflammatory cytokines such as IFN-g. Systemic or local
      treatment with somatostatin or somatostatin analogues has been shown to be
      beneficial in a number of in vivo models of autoimmune disease and chronic
      inflammation. In many of these models somatostatin appears to antagonise the
      effects of another neuropeptide, substance P. A somatostatin-substance P
      immunoregulatory circuit has been proposed to operate within murine Schistosoma
      mansoni-induced granulomas. In this review we extend the model of the
      somatostatin-substance P immunoregulatory circuit to include data derived from
      other biological systems, and those relying on human clinical situations. In
      addition, we present a hypothesis on the regulation of the default class of
      immune response within a tissue, based on the local balance of pro-and anti
      inflammatory neuropeptides.

PMID- 10903796
TI  - Pretreatment expression of the perforin gene by circulating CD8(+) T lymphocytes
      predicts biochemical response to interferon-alpha in patients with chronic
      hepatitis C.
AB  - It would be of great value to be able to predict, before the initiation of
      treatment, which patients with hepatitis C virus-induced chronic hepatitis will
      be cured by interferon-alpha (IFN-alpha). Competitive RT-PCR was used to evaluate
      spontaneous expression of the perforin gene, a marker of cytotoxic cell
      activation, by circulating mononuclear cells in 17 patients undergoing IFN-alpha
      treatment. IFN-alpha increased perforin gene expression (p < 0.003), but this was
      not correlated with outcome. In contrast, pretreatment perforin gene expression
      levels were higher in the 8 patients with a sustained biochemical response after
      treatment than in the 9 non-responsive patients (p = 0.01). This factor predicted
      favorable clinical outcome with a sensitivity of 75% and a specificity of 89%.
      Thus, pretreatment immunological status has a major influence on the ability of
      IFN-alpha to cure chronic hepatitis C, and the evaluation of perforin gene
      expression may help to select patients that will benefit from IFN-alpha
      treatment.

PMID- 10903797
TI  - R- and S-isomers of nonsteroidal anti-inflammatory drugs differentially regulate
      cytokine production.
AB  - 2-arylpropionic acids, a well known class of non-steroidal anti-inflammatory
      drugs (NSAIDs), exist as a racemic mixture of their enantiomeric forms, with S
      isomers primarily responsible for inhibition of prostaglandin (PG) production and
      of inflammatory events. In this study we show that S-isomers are also responsible
      for the paradoxical up-regulation of tumor necrosis factor (TNF) induced by
      ketoprofen, flurbiprofen and ibuprofen in murine peritoneal macrophages
      stimulated by bacterial endotoxin (LPS). This effect is in close correlation with
      cyclooxygenase inhibitory capacity of S-isomers and, from Northern blot analysis,
      seems to be mediated by the up-regulation of TNF mRNA. In addition, up-regulation
      of TNF production by S-isomers is associated with inhibition of interleukin-10
      (IL-10) production. Conversely, we have observed that S-enantiomers reduce IL-6
      production at a concentration 100 times higher than that able to inhibit
      cyclooxygenase activity. The unwanted pro-inflammatory effects of S-isomers
      through TNF and IL-10 production could therefore hinder their analgesic effect,
      that is, at least in part, related to IL-6 inhibition. In addition, TNF
      amplification by S-isomers could be correlated to the clinical evidence of their
      gastric toxicity. On the other hand, R-isomers did not affect TNF and IL-10
      production even at cyclooxygenase-blocking concentration, while they reduced IL-6
      production to the same levels as S-isomers. It is concluded that the regulation
      of cytokine production by S-isomers of 2-arylpropionic acids could partially mask
      their therapeutic effects and could be correlated to the clinical evidence of
      their higher gastric toxicity. On the other hand, IL-6 inhibition without the
      unwanted effects on TNF and IL-10 production shown by R-isomers could be
      correlated to the analgesic effect reported for R-2-arylpropionic acids.

PMID- 10903799
TI  - Subunit structure of the high and low affinity human interleukin-15 receptors.
AB  - Radio-iodinated cytokines and monoclonal antibodies directed at the IL-2R beta-
      and gamma-chains were used to analyze the structure of the cell-surface IL-15 and
      IL-2 receptors expressed by the human lymphoma cell clone YT-2C2. YT-2C2 cells
      are IL-2R alpha negative and express IL-2R gamma (15,000 molecules/cell) in
      excess of IL-2R beta (11,000 molecules/cell). Accordingly, they display a number
      of beta/gamma complexes of intermediate affinity for IL-2 and IL-15 which is
      equivalent to the number of beta-chains. Both cytokines compete for binding to
      this beta/gamma complex. There are about 800 high affinity IL-15 receptors,
      suggesting the presence of a similar number of IL-15R alpha-chains. Within the
      common intermediate affinity beta/gamma-complex, the anti-beta-chain A41 mAb
      defines an epitope which is similarly engaged in IL-2 and IL-15 binding, whereas
      the anti-beta-chain 284 mAb defines an epitope which does not display similar
      interaction with either cytokines. Thus, although IL-2 and IL-15 compete for
      binding to this beta/gamma-complex, they do not use similar binding areas. Cross
      linking and immunoprecipitation experiments have shown that the high affinity IL
      15 receptors comprises IL-2R beta/gamma, in association with IL-15R alpha and
      that the three chains can be efficiently cross-linked to IL-15 and co
      immunoprecipitated. Contrary to the intermediate affinity situation, high
      affinity IL-15 binding and subunit cross-linking were not affected by excess
      amounts of IL-2, A41 or 284 mAb, suggesting that when engaged in the IL-15 high
      affinity complex, the beta- and gamma-chains adopt different conformations, at
      least with respect to IL-15 binding. Finally, we provide evidence for the
      participation of a novel 35 kDa component within the high affinity structure.
      This component is immunoprecipitated with anti-IL-2R gamma mAb but not with anti
      IL-2R beta mAb and might correspond to a truncated form of IL-2R gamma-chain.

PMID- 10903798
TI  - Interleukin-18 mRNA, but not interleukin-18 receptor mRNA, is constitutively
      expressed in islet beta-cells and up-regulated by interferon-gamma.
AB  - Interleukin-18 (IL-18) mRNA is expressed in islets of NOD mice during the early
      stages of insulitis and IL-18 has therefore been implicated as a contributing
      factor in immune-mediated beta-cell destruction. However, a recent study failed
      to show any effect of human IL-18 on the function of isolated rat islets. Since
      species differences have been shown between human and murine IL-18, the aims of
      this study were to investigate 1) if species homologous IL-18 alone or following
      IL-12 pre-exposure affected rat islet function, 2) if IL-18 dose-dependently
      modulated IL-1 beta or interferon-gamma (IFN-gamma) + tumor necrosis factor-alpha
      (TNF-alpha) actions on islet function, and 3) if IL-18 and IL-18 receptor (IL
      18R) were expressed in rat islet beta-cells. Insulin release and nitric oxide
      (NO) production from isolated rat islets were measured after incubation with or
      without cytokines. RT-PCR was used to quantitate mRNA expression of IL-18 and the
      IL-18R signaling chain (IL-18R beta). There were no significant effects of 0.625
      10 nM recombinant murine (rm) IL-18 alone on accumulated or glucose-challenged
      insulin release or NO production after 24 hours. Fifteen pg/ml of recombinant
      human (rh) IL-1 beta as well as 200 U/ml recombinant rat (rr) IFN-gamma + 250
      U/ml rhTNF-alpha significantly increased islet NO production and inhibited both
      accumulated and glucose-challenged islet insulin release. However, rmIL-18 failed
      to modulate these effects of IL-1 beta or IFN-gamma + TNF-alpha. Although IL-12
      induces IL-18R expression in Th1 and B lymphocytes, 24-hours rmIL-12
      preincubation neither sensitized islets to effects of 10 nM of rm or rrIL-18
      alone nor primed the islets to IL-1 beta actions on insulin release and NO
      production. IL-18R beta mRNA, which was expressed in human peripheral blood
      mononuclear cells (PBMC), was not expressed in rat insulinoma (RIN) cells or in
      isolated rat islets, even after exposure to IL-1 beta and/or IFN-gamma + TNF
      alpha or IL-12. IL-18 mRNA was constitutively expressed in RIN cells, in FACS
      purified rat beta-cells and in intact rat and mouse islets, and was up-regulated
      by IFN-gamma in an interferon regulatory factor-1- IRF-1) and NO - independent
      manner. However, IL-18 protein was undetectable in lysates and supernates of RIN
      cells by ECL, Western blotting and immunoprecipitation. In conclusion, we show
      for the first time that IL-18 but not IL-18R is expressed in rodent islet beta
      cells. The physiological importance and pathological role of IL-18 originating
      from islet beta-cells deserve further investigation.

PMID- 10903800
TI  - Interleukin-2 expanded lymphocytes from lymph node and tumor biopsies of human
      renal cell carcinoma, breast and ovarian cancer.
AB  - Adoptive immunotherapy with immune effector cells has proved to be potent for
      treatment of tumors, however neither the attendant criteria for potential
      clinical efficacy of the injected cells, nor the method to prepare these cells
      are presently well established. Our procedure of collecting lymphocytes from
      biological samples, was based on the use of low IL-2 concentrations (90 to 150
      IU/ml) and on the stringent separation of lymphocytes from tumor cells at the
      very early stages of their outgrowth in culture. When lymphocytes were derived
      from tumor biopsies (TIL), we observed differences depending on the histological
      type of tumor. In renal cell carcinoma, natural killer cells were expanded in
      4/11 biopsies contrary to what was observed in breast cancer (92 +/- 5% of T
      lymphocytes from 9 biopsies). The outgrowth of lymphocytes from breast tumors was
      slower and lower than from renal carcinomas. The autologous tumor cell line was
      more difficult to obtain from breast carcinoma (23%) than from renal cell
      carcinoma (61%) biopsies. For ovarian cancer, short-term culture of tumor cells
      could be obtained for half of the tumor-invaded biological samples. Eight of the
      23 tumor-derived cultures contained more than 40% CD8 T. TIL were consistently
      cytolytic each time they could be evaluated. For ascitic and pleural fluids, data
      were of similar range. In ascitic-derived cultures, tumor cells and antigen
      presenting cells are present and can be supposed to rechallenge T cells with
      tumor antigens. Lymphocytes derived from lymph nodes could be expanded to a
      larger number than TIL. However, only 1/18 of these cultures contained more than
      40% CD8 T. The presence of few tumor cells in this culture was in favor of
      significant specific and non-specific cytotoxicity in RCC lymph node cultures and
      higher percentages of CD8 T in breast cancer lymph nodes. Correlations could not
      be established between CD8 T percentages and specific in vitro cytotoxicity in
      our polyclonal populations. Our conclusion is that phenotypic and functional
      quality of lymphocytes is of interest when the T cells are derived 1) from tumors
      (RCC, breast or ovarian cancer) and isolated very early to avoid inhibitor
      factors secreted from tumor cells or 2) from lymph nodes and ascitic and pleural
      fluids when very few tumor cells are co-cultivated with lymphocytes at initial
      steps of culture. Final expansion to a number of lymphocytes suitable for therapy
      (> 109) could be attained in a second step of the procedure by the use of 1,000
      IU/ml IL-2 each time it was assayed with 50.106 lymphocytes. In view of these
      data it appears that phenotypic and functional changes occur during culture
      depending on the presence of a particular ratio of tumor antigens. This could be
      artificially reproduced.

PMID- 10903801
TI  - Lck is involved in interleukin-2 induced proliferation but not cell survival in
      human T cells through a MAP kinase-independent pathway.
AB  - The role of Lck in IL-2-induced proliferation and cell survival is still
      controversial. Here, we show that the Src family kinase inhibitor, PP1, reduced
      the IL-2-induced proliferation of human T cells significantly without inhibiting
      the anti-apoptotic effect of IL-2. As Lck is the only Src family kinase activated
      upon IL-2 stimulation in T cells, this indicates that Lck is involved in IL-2
      induced proliferation but not survival. IL-2-induced MAP kinase activation was
      only slightly inhibited by PP1, suggesting that Lck is not essential for IL-2
      induced MAP kinase activation in human T cells. We found that an IL-2-sensitive,
      human mycosis fungoides-derived tumor T cell line is Lck negative, and that the
      IL-2-induced MAP kinase activation is comparable to non-cancerous T cells,
      although a little delayed in kinetics. An Lck expressing clone was established by
      transfecting Lck into mycosis fungoides tumor T cells, but Lck had no influence
      on the delayed kinetics of MAP kinase activation, indicating that Lck is not
      essential for MAP kinase activation in mycosis fungoides tumor T cells or in non
      cancerous T cells. Taken together, this indicates that Lck is involved in IL-2
      induced proliferation, but not cell survival, through a pathway not involving MAP
      kinase.

PMID- 10903802
TI  - Transforming growth factor-beta(1), -beta(2), -beta(3), basic fibroblast growth
      factor and vascular endothelial growth factor expression in keratinocytes of burn
      scars.
AB  - Keratinocytes are increasingly recognized as key regulators of skin inflammation
      and remodeling, as they are capable of producing growth factors and cytokines
      that are important mediators in the wound healing process. We investigated the
      expression and distribution of TGF-beta 1 mRNA by mRNA in situ hybridization and
      of TGF-beta 1, TGF-beta 2, TGF-beta 3, bFGF and VEGF protein expression using
      immunohistochemistry in spontaneously healed, partial-thickness burns and
      compared this with the expression of these markers in matched unburned skin. This
      was done to assess their role in the remodeling phase of burn wound healing.
      Punch biopsies were taken from both partial-thickness burns after re
      epithelialization and from matched, unburned skin. At 4 and 7 months post-burn,
      biopsies were taken of normotrophic and hypertrophic scars that had developed in
      these wounds. We observed a higher expression of all mentioned growth factors in
      keratinocytes in scars at 1 month post-burn compared with matched unburned skin.
      At 4 months, keratinocytes still displayed a higher expression of TGF-beta 3 and
      bFGF, but the expression of TGF-beta 1, TGF-beta 2 and VEGF was normalized. The
      expression of TGF-beta 3 in the epidermis of hypertrophic scars was slightly
      higher than in normotrophic scars. At 7 months post-burn, all growth factors
      studied showed a normal expression on keratinocytes. Our results suggest that
      keratinocytes are not only involved in re-epithelialization, but also in the scar
      maturation. The data support the idea that keratinocytes not only respond to
      cytokines and growth factors in an autocrine fashion, but also exert regulatory
      paracrine effects on contiguous cells.

PMID- 10903803
TI  - Interleukin-13 and IgE production in rat experimental schistosomiasis.
AB  - We have previously demonstrated in rat experimental schistosomiasis an
      upregulation of IL-4 expression at the mRNA and protein levels which could
      explain, at least in part, the increased IgE production observed during
      infection. Using this model, we have investigated the expression of IL-13 which
      is also involved in the induction of the IgE response. In the present study, we
      have shown a significant increase in IL-13 mRNA expression in spleen, liver and
      lungs following primary and secondary infection. IL-13 protein was detected by
      intracellular staining in spleen cells from infected rats, and in the
      supernatants of antigen-stimulated spleen cells. Furthermore, circulating levels
      of IL-13 were increased in sera from infected rats as compared to those from non
      infected control animals. These findings show that, similarly to IL-4, IL-13 is
      upregulated and secreted during rat schistosomiasis, suggesting an involvement of
      both cytokines in IgE induction. In the in vivo experiments, only rats cotreated
      with neutralizing anti-IL-4 and anti-IL-13 antibodies showed significant decrease
      in the IgE levels. Moreover, administration of IL-13 enhanced total IgE levels.
      These results demonstrate the implication of IL-4 and IL-13 in vivo in IgE
      production, and provide a relevant animal model for a better understanding of the
      role of IL-4 and IL-13 in humans.

PMID- 10903804
TI  - A rare allele combination of the interleukin-1 gene complex is associated with
      high interleukin-1 beta plasma levels in healthy individuals.
AB  - Increases in the plasma levels of the inflammatory cytokines can be detected in
      various infectious and inflammatory diseases, but in healthy individuals these
      levels are in most cases low or undetectable. There is now increasing evidence
      that genes of the inflammatory cytokines are polymorphic and the various alleles
      may differ in their capability to produce the cytokine. We have measured the
      plasma levels IL-1 beta of 400 healthy blood donors and correlated these to the
      genotype (biallelelic base exchanges at the position - 889 of the IL-1 alpha
      gene, and at the position - 511 of the IL-1 beta gene and the pentaallelic VNTR
      in the second intron of the IL-1Ra gene). The median concentration of IL-1 beta
      was 5.8 pg/ml (upper and lower quartiles 2.2-13.6). The polymorphisms of the IL-1
      beta and IL-1 Ra genes did not have any significant influence on the IL-1 beta
      levels, but the IL-1 alpha 2.2 homozygotes (32/400 blood donors) had
      significantly elevated levels (median 7.0 pg/ml, quartiles 2.2-22.4, one-way
      ANOVA p < 0.008 as compared to the IL-1 alpha 1.1 homozygotes and p < 0.02 as
      compared to the IL-1 alpha 1.2 heterozygotes). This effect of IL-1 alpha 2.2
      homozygosity was more pronounced in donors, who also were carriers of the IL-1
      beta allele 2. Thus these data suggest that this allele combination has a
      regulatory effect on basal IL-1 beta production.

PMID- 10903805
TI  - Neutrophil alpha-defensin human neutrophil peptide modulates cytokine production
      in human monocytes and adhesion molecule expression in endothelial cells.
AB  - Defensins, a family of small, cationic, antimicrobial peptides, are found in
      mammals, insects and plants. alpha-defensins are stored in granules of
      neutrophils and released upon activation by exocytosis. It was shown here that
      human neutrophil peptide (HNP), at concentrations of 10(-8) -10(-9) M, up
      regulated the expression of TNF-alpha and IL-1 beta in monocytes activated with
      Staphylococcus aureus or PMA, while expression of IL-10 mRNA was down-regulated
      and production of IL-8 was not affected. HNP alone was unable to induce TNF-alpha
      or IL-1 beta expression in resting monocytes. At concentrations of 10(-4) -10(
      5)M, HNP was cytotoxic for monocytes in serum-free medium. The cytotoxicity was
      abrogated in the presence of serum, while a cytokine-modulating effect of HNP was
      observed in the presence of serum and in whole blood, suggesting that this
      mechanism may function in vivo. Similarly, serum did not abrogate bactericidal
      activity of HNP. It was also demonstrated herein that HNP at 10 (-8) -10(-9) M,
      attenuated the inhibitory action of dexamethasone on TNF-alpha production. In
      parallel to monocyte studies, we have showed that HNP at concentrations ranging
      from 10(-9)M to 10(-6)M caused about 5-fold suppression of VCAM-1 expression in
      TNF-alpha-activated human umbilical vein endothelial cells, while the ICAM-1
      expression was not affected. Our findings suggest that neutrophil defensins have
      the potential to modulate the inflammatory responses through regulation of
      cytokine production and adhesion molecule expression.

PMID- 10903806
TI  - Activation of extracellular signal-regulated kinase (ERK)1/2 contributes to
      cytokine-induced apoptosis in purified rat pancreatic beta-cells.
AB  - Cytokines may contribute to beta-cell apoptosis in the early stages of type 1
      diabetes mellitus. It has been reported recently that interleukin-1 beta (IL-1
      beta) induces activation of the mitogen-activated protein kinases (MAPK) p38 and
      ERK1/2 in neonatal rat islets. Since these kinases may participate in cytokine
      induced apoptosis, we evaluated whether cytokines induce activation of MAPKs in
      FACS-purified primary rat beta-cells, and whether blockers of p38 and/or ERK1/2
      prevent beta-cell death. IL-1 beta, but not interferon-gamma (IFN-gamma), caused
      phosphorylation of the substrates Elk-1, ATF-2 and hsp25, and the phosphorylation
      of both Elk-1 and hsp25 were decreased by the p38 blocker SB203580 (p38i) and the
      MAPK/ERK blocker PD 098059 (MEKi). When added together, p38i and MEKi decreased
      IL-1 beta-induced nitrite production over 24 hours by 60%, but did not affect IL
      1 beta-induced manganese superoxide dismutase (MnSOD) mRNA expression. To test
      the effects of MAPK inhibitors on beta-cell death by necrosis or apoptosis, these
      cells were exposed for 6 or 9 days to IL-1 beta + IFN-gamma. This treatment
      induced cell death, mostly by apoptosis. The MEKi, but not the p38i,
      significantly decreased cytokine-induced apoptosis, thus decreasing the total
      number of dead cells. This protection was only partial, suggesting that ERK1/2
      activation is not the only mechanism by which cytokines induce beta-cell
      apoptosis. We conclude that IL-1 beta induces activation of both p38 and ERK1/2,
      and that ERK1/2 contributes to the pro-apoptotic effects of the cytokine in
      primary beta-cells.

PMID- 10903807
TI  - Inhibition of NO production in macrophages by IL-13 is counteracted by Herpes
      simplex virus infection through tumor necrosis factor-alpha-induced activation of
      NK-kappa B.
AB  - Interleukin (IL)-13 is known to antagonize many interferon (IFN)-gamma-activated
      functions in macrophages and among these, nitric oxide (NO) production. We have
      previously shown that this function of IL-13 is reduced in Herpes simplex virus
      type 2 (HSV-2)-infected macrophages. In the present study we show that IL-13 and
      IFN-gamma are indeed produced during infection of BALB/c mice with HSV-2. The
      lack of inhibitory function of IL-13 in infected macrophages, which was not
      overcome even at very high concentrations of IL-13, was not due to impaired IL-13
      signalling, since virus infection did not affect IL-13-mediated activation of
      STAT6 (signal transducer and activator of transcription 6). Neutralizing tumour
      necrosis factor (TNF)-alpha antibodies, however, largely restored the effect of
      IL-13 on NO production in virus-infected macrophages. The same was observed after
      treatment of the cells with inhibitors of nuclear factor (NF)-kappa B activation,
      known to be involved in enhancement of IFN-gamma-induced NO production. Even
      though IL-13 reduced TNF-alpha secretion by 50%, this did not impair NF-kappa B
      activation in IFN-gamma-treated cells infected with HSV-2. The results indicate
      that TNF-alpha, secreted by virus-infected macrophages, activates NF-kappa B
      which impairs the IL-13-mediated inhibition of inducible NO synthase (iNOS)
      expression. This could imply that a sustained NO production would be focused to
      sites of active virus replication.

PMID- 10903808
TI  - Expression of neurotrophin receptors in normal and malignant B lymphocytes.
AB  - In order to define a cellular model suitable for studying, in vitro, the
      molecular properties and functions of neurotrophin receptors in human
      lymphocytes, TrkA, TrkB, TrkC and p75(NTR) expression was investigated in a panel
      of EBV immortalized lymphoblastoid (LCL) and Burkitt lymphoma-derived cell lines
      (BLs) compared to primary B lymphocytes by RT-PCR and flow cytometric analysis.
      Our data show that trkA and trkB are transcribed in most B cell lines of normal
      and malignant origin. For several of them, we also gained first evidence of trkC
      expression in B cells. All cell lines and primary B cells lack p75(NTR)
      expression. These data suggest that neurotrophin receptors expression in the B
      cell lines correlates to some extent with the phenotypic maturation stage and
      endogenous viral activity levels. Our data suggest that TrkA and TrkB, once
      activated, provide a partial rescue from apoptosis, whereas TrkC stimulates the
      progression through the cell cycle without affecting cell survival. Finally, the
      identification of a number of cell lines showing single expression of one of the
      Trk receptors has disclosed the availability of a cellular tool for further
      studies on their function, and mechanisms of signal transduction in the B cell
      moiety in the absence of p75(NTR).

PMID- 10903809
TI  - Prostaglandin B(2) delivers a co-stimulatory signal leading to T cell activation.
AB  - Most of the data accumulated to date on the immunoregulatory effects of
      prostaglandins (PG) on T cell activation stem from the archetypal inhibitory
      effect of PGE(2). In this study we provide instead, the first evidence that
      exogenous PGB(2), a catabolic metabolite of PGE(2), synergizes with signals
      delivered by T cell receptor (TCR) engagement to induce interleukin-2 (IL-2)
      production and IL-2 receptor (IL-2R) alpha-expression in Jurkat cells.
      Accordingly, PGB(2) enhances the proliferation of anti-CD3-activated peripheral
      blood lymphocytes (PBL). In terms of cellular signaling, we present evidence that
      PGB(2) activates tyrosine kinase activities and efficiently increases c-fos mRNA
      expression and nuclear factor-kappa B (NF-kappa B) translocation to the nucleus.
      Owing to these features, PGB(2) appears as a new lipid mediator capable of
      delivering an ancillary signal leading to T lymphocyte activation.

PMID- 10903810
TI  - Stimulatory and inhibitory regulators of the hypothalamo-pituitary-adrenocortical
      axis.
AB  - Short- and long-term metabolic effects of stress are mediated through the
      hypothalamo-pituitary-adrenocortical (HPA) axis and the sympathetic nervous
      system. While efficient functioning of these systems is essential for life
      processes, dysfunction can lead to hypercortisolaemia and inappropriately
      elevated catecholamines, resulting in immunosuppression and associated
      pathologies. This review will concentrate on the central mechanisms involved in
      the control of HPA axis activity, particularly neuronal, neuropeptide and
      transcriptional input to CRF and AVP expression in the hypothalamus. The emphasis
      of the article will be on our increased understanding of selective and specific
      responses of the HPA axis to different types of stressors. Elucidating the
      biochemical mechanisms underlying stress may permit the development of
      pharmacological strategies to treat chronic stress which exacts such a major toll
      on our quality of life today.

PMID- 10903811
TI  - Regulation of the hypothalamo-pituitary-adrenal axis by cytokines.
AB  - Many of the pro-inflammatory cytokines which are released in response to
      immune/inflammatory insults exert marked stimulatory influences on the
      hypothalamo-pituitary-adrenocortical (HPA) axis; they thus provoke the release of
      glucocorticoids which, in turn, temper the ensuing immune-inflammatory response
      and thereby complete a homeostatic neuroendocrine-immune regulatory loop. This
      article reviews the putative mechanisms by which cytokines, released acutely in
      response to such insults, activate the HPA axis, placing particular emphasis on
      the actions and interactions of tumour necrosis factor-alpha (TNF-alpha),
      interleukin-1 (IL-1) and interleukin-6 (IL-6) and on the counter-regulatory
      mechanisms that are in place.

PMID- 10903812
TI  - Delayed effects of stress and immune activation.
AB  - Stress responses play a crucial adaptive role but impose potentially subversive
      demands on the organism. The same holds for the symptoms of illness as seen after
      immune activation by pathogens or tissue damage. The responses to immune stimuli
      and stressors show remarkable similarities and rely on similar control mechanisms
      in the brain: i.e. they involve neuropeptides of the corticotropin releasing
      factor (CRF) family. Immune and non-immune challenges lead to responses that
      normally show a temporal relationship with the duration and intensity of the
      stimulus and the (re)activity of the stress-responsive systems return to their
      pre-challenged state within hours or days. However, exposure of animals or man to
      specific stimuli can induce delayed and long-lasting (weeks, months) alternation
      in stress responsive systems, resulting in a prolonged period of increased stress
      vulnerability. Immune stimuli are particularly powerful in eliciting such a
      stress vulnerable state. Various adaptive changes in the (neuro)biological
      substrate as seen during this stress vulnerable state also occur in depression,
      and may be causally related to the depressive symptoms that are often associated
      with infectious and inflammatory diseases.

PMID- 10903813
TI  - Corticotropin-releasing factor antagonists, binding-protein and receptors:
      implications for central nervous system disorders.
AB  - Corticotrophin-releasing factor (CRF; interchangeable with corticotrophin
      releasing hormone, CRH) is a neurohormone family of peptides which implements
      endocrine, physiological and behavioural responses to stressor exposure. Built-in
      biological diversity and selectivity of CRF system function is provided by
      multiple endogenous ligands and receptors which are heterogeneously distributed
      in both brain and peripheral tissues across species. At present, there are at
      least five distinct targets for CRF with unique cDNA sequences, pharmacology and
      localization. These fall into three distinct classes, encoded by three different
      genes and have been termed the CRF1 and CRF2 receptors and the CRF-binding
      protein. Significant gains in knowledge about the physiological role of CRF
      binding sites in brain have emerged recently due to the proliferation of novel,
      high-affinity, receptor-selective pharmacological tools as well as multiple knock
      out and knock-in mutant mouse models. These results support a role for CRF
      binding sites in co-ordinating stress reactivity, emotionality and energy balance
      over the life-span of the organism.

PMID- 10903814
TI  - Chronic inflammatory stress.
AB  - A major mechanism involved in maintaining homeostasis in response to chronic
      inflammation is the hypothalamo-pituitary-adrenal (HPA) axis, resulting in the
      release of anti-inflammatory glucocorticoids from the adrenal cortex. An
      inadequate HPA axis response may result in the development of a pathology or an
      increase in susceptibility and/or severity of disease. Other neuroendocrine
      systems are also implicated. Increasingly considered important are circadian
      rhythms, not only of hormones, but also of components of the immune system.
      Recent evidence concerning changes in hypothalamic control of the HPA axis
      following development of disease, the implication of these for the response to
      stress and the use of the HPA axis as a predictor of susceptibility to disease
      will also be considered. Finally, the influence of stress on autoimmune disease
      will be discussed. This chapter will concentrate principally on rheumatoid
      arthritis, although other autoimmune diseases and animal models will be
      discussed.

PMID- 10903815
TI  - Glucocorticoids and immune function.
AB  - The prevailing notion has been that cytokines such as interleukin-1 released from
      sites of inflammation cross the blood-brain barrier and drive the hypothalamo
      pituitary-adrenal (HPA) axis so that cortisol is released into the circulation to
      exert indiscriminate systemic anti-inflammatory effects. It is now clear that
      feedback from the HPA axis is subject to more subtle and localized regulation.
      The signal that activates cortisol release travels to the hypothalamus via vagal
      sensory afferents (so the brain 'knows' where the inflammation is), and the
      effects of the released cortisol are regulated within individual tissues via
      numerous mechanisms, including changes in the affinity of the cortisol receptors,
      and changes in the equilibrium point of the cortisol/cortisone shuttle (11 beta
      hydroxysteroid dehydrogenases 1 and 2). This equilibrium is locally regulated by
      cytokines. These mechanisms are central to the regulation of the balance of Th1
      to Th2 cytokines within sites of inflammation, and to the appropriate or
      inappropriate termination of the inflammatory response in infections or
      autoimmunity.

PMID- 10903816
TI  - Stress, cytokine patterns and susceptibility to disease.
AB  - Recent evidence indicates that glucocorticoids and catecholamines, the end
      products of the stress system, and histamine, a product of activated mast cells,
      might selectively suppress cellular immunity, and favour humoral immune
      responses. This is mediated by a differential effect of stress hormones and
      histamine, on T helper 1 (Th1)/Th2 patterns and type 1/type 2-cytokine
      production. Thus, systemically, stress might induce a Th2 shift, while, locally,
      under certain conditions, it might induce pro-inflammatory activities through
      neural activation of the peripheral corticotropin-releasing factor-mast cell
      histamine axis. Through the above mechanisms, stress may influence the onset
      and/or course of infectious, autoimmune/inflammatory, allergic and neoplastic
      diseases.

PMID- 10903818
TI  - Stress and coping: the psychoneuroimmunology of HIV/AIDS.
AB  - A considerable body of evidence, reviewed in this chapter, suggests that
      psychosocial factors play an important role in progression of HIV infection, its
      morbidity and mortality. Psychosocial influences relating to faster disease
      progression include life-event stress, sustained depression, denial/avoidance
      coping, concealment of gay identity (unless one is rejection-sensitive), and
      negative expectancies. Conversely, protective psychosocial factors include active
      coping, finding new meaning, and stress management. In studying long survivors of
      HIV/AIDS, our group has found protective effects on health of life involvement,
      collaborative relationship with doctor, emotional expression, depression
      (conversely), and perceived stress (conversely). Reviewed and discussed are
      psychoneuroimmunological pathways by which immune and neuroendocrine mechanisms
      might link psychosocial factors with health and long survival. Finally,
      biological factors are also a major determinant of disease progression and
      include genetics and age of the host, viral strain and virulence, medication and
      several immune response factors on which psychosocial influences could impact.

PMID- 10903817
TI  - Glucocorticoids and depression.
AB  - Depression has been associated with impaired mineralocorticoid receptor function,
      restrained glucocorticoid receptor feedback at the level of the hypothalamic
      pituitary-adrenal (HPA) axis, raised cortisol level and increased corticotropin
      releasing factor activity, which may act in concert to induce the signs and
      symptoms of the disorder. Pre-clinical and clinical evidence suggests that both
      genetic and environmental factors contribute to the development of these HPA axis
      abnormalities in depressed patients. Support for this view derives from models
      using genetically modified animals and/or chronic stress exposure at different
      developmental stages, although all of the current approaches have to be viewed
      within their limitations to model the disease. However, both animal and human
      studies challenging the HPA system show at least some neuroendocrine and
      behavioural changes comparable to those seen in depression, suggesting that some
      of the depressive symptoms can be attributed to HPA axis hyperactivity. Moreover,
      normalization of the neuroendocrine function following chronic antidepressant
      drug treatment seems to be a prerequisite for stable remission of depressive
      psychopathology, i.e. that normalization of HPA function is critical for relief
      of the clinical symptomatology of this disorder.

PMID- 10903819
TI  - The cyanide leaching gold recovery process is a nonsustainable technology with
      unacceptable impacts on ecosystems and humans: the disaster in Romania.
AB  - The statements and discussions in this commentary are based on the disastrous
      situation near Baia Mare in Romania, where a dam of a cyanide basin burst on
      January 30, 2000, with serious consequences.

PMID- 10903820
TI  - Toxic effects and bioaccumulation of cadmium in the aquatic oligochaete Tubifex
      tubifex.
AB  - Although Tubifex tubifex (Oligochaeta, Tubificida) has been proposed as a test
      organism for ecotoxocological studies, very few data concerning sublethal
      toxicity and bioaccumulation are available on this worm. The aims of this work
      were to assess the toxicity of cadmium, one of the most toxic metals frequently
      encountered in polluted areas, on T. tubifex and the ability of the worm to
      accumulate this metal. Acute toxicity was analyzed by measurement of the 96-h
      LC(50) and daily survival rates. Results indicated that T. tubifex undergoes an
      adaptation period to Cd, the duration of which decreases with increasing Cd
      concentration. The various parameters affecting toxicity are discussed. Sublethal
      toxicity was studied by scanning electron microscopy. Observations revealed that
      Cd induced autotomy of the caudal region and mucus production. Autotomy is
      proposed as a criterion for sublethal toxicity. The results of bioaccumulation
      studies revealed that Cd is highly and rapidly taken up by the worm, suggesting
      involvement of efficient detoxification mechanisms. Consequently, the ability to
      accumulate large amounts of Cd may represent a potential toxicological risk to
      predators of the worm if Cd is accumulated in bioavailable forms.

PMID- 10903821
TI  - Distribution, transformation, and long-term accumulation of polychlorinated
      dibenzo-p-dioxins and dibenzofurans in different tissues of fish and piscivorous
      birds.
AB  - The present study monitored 10-year-old fish and piscivorous birds from sites
      contaminated for many years. The data reflected the results of actual, long-term
      environmental exposures. The results demonstrate that different tissues of fish
      have quite different concentrations of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/F). The concentration order of PCDD/F within fish is liver
      congruent with egg congruent with intestine>kidney congruent with heart>gill
      congruent with bladder>muscle>brain. The concentration order of PCDD/F within
      piscivorous birds was liver>egg congruent with heart>muscle congruent with
      stomach>brain. The results obtained also demonstrate that the accumulation
      patterns of piscivorous birds and fish are quite different. The tissues of fish
      and piscivorous birds have different capacities for bioaccumulation and
      biotransformation of PCDD/F; variable proportions of TEQs were also found
      throughout their bodies. In fish, toxic equivalency quotient (TEQ): PCDD/F ratios
      in various tissues ranged from 0.01 to 0.07, whereas in birds the ratios ranged
      from 0.07 to 0.43. If the concentrations are normalized with lipid content, the
      results vary less. The effect of different lipid properties is obvious in the
      case of brain tissue, which is richer in phospholipids.

PMID- 10903822
TI  - Differential inhibition of xenobiotic-metabolizing carboxylesterases by
      organotins in marine fish.
AB  - The hydrolytic metabolism of xenobiotics in the liver of two tropical marine
      fish, Siganus canaliculatus and Acanthopagrus latus, was found to be catalyzed by
      both microsomal and cytosolic carboxylesterases; the latter forms were more
      active than the former. Remarkably greater efficiency of S. canaliculatus for p
      nitrophenylacetate hydrolysis was attributed to manyfold higher V(max) and lower
      K(m) values of hepatic microsomal and cytosolic carboxylesterases of S.
      canaliculatus as compared with those of A. latus. Comparative characterization of
      the in vitro responses of hepatic microsomal and cytosolic carboxylesterases to
      the organotin group of marine pollutants-tributyltin (TBT), triphenyltin (TPT),
      and dibutyltin (DBT), a relatively persistent metabolite of TBT-revealed species
      , isozymic form-, and organotin structure-related differences in the hydrolytic
      detoxication. In general, carboxylesterases of S. canaliculatus exhibited
      severalfold greater susceptibility to organotin inhibition and DBT was the most
      potent inhibitor (IC(50) in micromolar range). Notably, the IC(50) of SnCl(2), a
      metal present in all the compounds studied, was higher than 2 mM. Cytosolic forms
      in both species were more sensitive to organotin inhibition than microsomal
      counterparts. In line with these differences the nature of inhibition of
      cytosolic and microsomal carboxylesterases by organotins was competitive and
      noncompetitive, respectively. These results suggest that organotins may aggravate
      the toxicity of other environmental contaminants in fish and other aquatic
      organisms. Moreover, highly sensitive cytosolic carboxylesterases of S.
      canaliculatus liver may serve as molecular biomarkers of organotin pollution.

PMID- 10903823
TI  - Relationship of lead and cadmium to essential elements in hair, teeth, and nails
      of environmentally exposed people.
AB  - The aim of this investigation was to evaluate the environmental exposure to Pb
      and Cd during 1990-1997 of inhabitants of Katowice District, which is an area of
      high environmental exposure to lead and cadmium, as well as exposure to Fe, Zn,
      Cu, Mn, Ni, Cr, Ca, Na, and K, on the basis of concentrations in hair, teeth, and
      nails. This investigation was to explain if accumulation of Pb and Cd can affect
      the concentration of such essential metals as Fe, Zn, Cu, and Ca. Inhabitants of
      the Beskid area constituted a control group. Analysis of the aforementioned
      elements was carried out on 624 hair samples, 785-tooth- samples, and 338 nail
      samples taking into consideration sex, age (<15, 16-30, >30 years), and type of
      teeth (incisor, canine, molar, premolar). Concentrations of elements in the media
      investigated were determined using atomic absorption spectroscopy. The results
      were calculated using the Statistica program. The major statistical analysis
      focuses on determining analysis of variance by MANOVA/ANOVA, Rao R (P<0.05),
      Spjotvolla-Stoline'a test, and cluster analysis (1-Pearson r). The investigation
      revealed that among the media investigated, Pb concentration in hair is an
      environmental marker of exposure to this metal in the human organism and depends
      on sex and age. It was also observed that an increase in Pb concentration in hair
      causes a decrease in Fe and Ca concentrations and changes the ratios of essential
      metals: Fe/Cu, Fe/Zn, and Ca/Zn. It is concluded that not only in blood but also
      in the hair, lead significantly influences Ca and Fe. Analysis of nail samples of
      people living in Katowice District indicated that an increasing concentration of
      Pb decreases concentrations of copper and zinc. Increased accumulation of such
      metals as Ni, Cr, and Mn in teeth was observed for samples taken from inhabitants
      of Katowice District.

PMID- 10903824
TI  - Mangifera indica and Phaseolus vulgaris in the bioindication of air pollution in
      Bahia, Brazil.
AB  - In this article are reported the results of a study on the concentration of
      ascorbic acid (AA) in Mangifera indica as passive monitor and in Phaseolus
      vulgaris as active monitor with the intention to study the effects of industrial
      emissions from the Petrochemical Complex of Camacari (PCC), Bahia, Brazil, on the
      vegetation. Leaves from M. indica were collected in two sites in the region under
      direct influence of industrial emissions and in one presumed nonpolluted
      reference (background) site. Pots with P. vulgaris were exposed in the same
      sites. The AA increase in the leaves of M. indica from PCC sites indicates a
      stress situation. The small AA increase in the P. vulgaris exposed in the more
      polluted site indicates that the active monitor is a sensitive one. The decrease
      of its leaf area indicates the inability of this species to activate
      physiological protection mechanisms like an increase in AA production.

PMID- 10903825
TI  - Radon hazards, geology, and exposure of cave users: a case study and some
      theoretical perspectives.
AB  - The concerns over the risks to human health from radon in underground caves are
      poorly documented, unlike in workplace or domestic environments where exposures
      are relatively well known. In U.K. caves, radon has been identified as occurring
      at elevated levels; but with the exception of major show caves, its impact and
      risk to the many groups who use the caves have thus far received inadequate
      attention. This paper presents a survey performed in a relatively "low-risk"
      geographical area of the United Kingdom and quantifies the risk of exposure in
      this cave environment. Radon levels up to 12,552 Bq m(-3) were measured: Such
      concentrations are very high but are likely to underestimate the levels in many
      other parts of the cave system, for reasons associated with cave architecture and
      meteorology. This study confirms previous workers' conclusions that long-term
      users of deep caves, as opposed to rock shelters, are at risk. Annual doses to
      certain groups of cave users have been calculated to be as high as 120 mSv, a
      very high value. The study also demonstrates that there is variation both within
      and between caves as a result of subtleties of the bedrock geology, fault
      patterns, and weathering. This paper sets out a theoretical model.

PMID- 10903826
TI  - Effect of toxaphene on isolated hepatocytes of the yellowtail flounder,
      Pleuronectes ferrugineus storer.
AB  - The histochemical and enzyme cytochemical effects of Toxaphene were investigated
      using isolated hepatocytes in suspension culture from laboratory-bred juvenile,
      female yellowtail flounder (Pleuronectes ferrugineus). Hepatocytes were kept in
      suspension culture for 4 days and exposed for 3 days to a control medium, to a
      medium with hexane (the solvent of Toxaphene), or to a medium with Toxaphene in
      two different concentrations (1 and 10 mocrog/ml). Subsequently, the cultivated
      cells were examined histochemically (Sudan black B, oil red O, Schmorl's
      reaction) and enzyme cytochemically (acid phosphatase, NADPH-ferrohemoprotein
      reductase). Toxaphene decreased the viability of the isolated cells
      significantly, as compared to the control suspensions. Toxaphene also increased
      the storage of total and neutral lipids (as demonstrated by Sudan black B and oil
      red O, respectively) in a dose-dependent manner. In addition, Toxaphene increased
      the enzymatic activity of acid phosphatase, and increased the storage of
      lipofuscin pigment (as demonstrated by the Schmorl's reaction) within the
      hepatocytes, suggesting an increase in the number and/or size of the lysosomes.
      Hexane did not have a significant toxic effect on the isolated hepatocytes. It is
      concluded that Toxaphene is potentially toxic to fish in a marine environment and
      that this in vitro system may provide a model for assessing the direct effect of
      various toxicants on fish hepatocytes.

PMID- 10903828
TI  - Environmental risk limits for two phthalates, with special emphasis on endocrine
      disruptive properties.
AB  - Environmental risk limits (ERLs) are derived for di-n-butyl phthalate (DBP) and
      di(2-ethylhexyl) phthalate (DEHP). The ERLs are derived using data on
      (eco)toxicology and environmental chemistry. Endpoints used are survival, growth,
      and reproduction. The resulting ERLs in water are 10 and 0.19 microg/L for DBP
      and DEHP, respectively; in fresh soil and sediment with 10% organic matter the
      derived ERLs are respectively 0.7 and 1 mg/kg fresh wt. In The Netherlands,
      measured concentrations of DBP are seldom above the ERLs, while reported
      concentrations for DEHP are 3 to 20 times higher than the ERL. As phthalates as a
      group are commonly mentioned as chemicals with possible endocrine disruptive
      effects, in vivo and in vitro tests for a series of phthalates with endpoints
      related to endocrine disruption are reviewed. In vitro and in vivo tests give a
      similar distinction between phthalates that can or cannot act as endocrine
      disrupters. The significance of these tests for the derivation of ERLs is
      discussed. It is concluded that the ERLs derived will give sufficient protection
      against endocrine disruptive effects. There is no need to include additional data
      for DBP and DEHP, related to endpoints other than survival, growth, or
      reproduction, in the derivation of ERLs.

PMID- 10903827
TI  - Bioaccumulation of selenium (Se) in the Cienega de Santa Clara wetland, Sonora,
      Mexico.
AB  - The Cienega de Santa Clara, on the east side of the Colorado River delta, is a
      brackish wetland supported by agricultural drainage water from the United States
      that provides habitat for endangered fish and bird species. Bioaccumulation of
      selenium has created toxicity problems for wildlife in similar wetlands in the
      United States. This is the first selenium survey in the Cienega de Santa Clara.
      Ten sites were selected to collect water (dissolved), sediments (total), plants,
      invertebrates, and fish. Samples were collected from October 1996 to March 1997.
      Selenium was detected in all samples. Concentrations in water ranged from 5 to 19
      microg/L and increased along a salinity gradient. Although water levels of
      selenium exceeded EPA criterion for protection of wildlife, levels in sediments
      (0.8-1.8 mg/kg), aquatic plants (0.03-0.17 mg/kg), and fish (2.5-5.1 mg/kg whole
      body, dry wt) did not exceed USFWS recommended levels. It is concluded from this
      study that the levels of selenium in water did not affect the overall health of
      the fish sampled. Therefore, it is important to maintain or improve the water
      quality entering this wetland to continue to have normal levels of Se in the food
      chain components.

PMID- 10903829
TI  - Absorption and distribution of selenium in animals consuming canola grown for
      selenium phytoremediation.
AB  - Canola (Brassica napus) grown as a selected plant species for field
      phytoremediation of selenium (Se) may be harvested and utilized as Se-enriched
      forage for marginally Se-deficient lambs and cows. Two field studies were
      conducted under controlled conditions to evaluate the accumulation of Se into
      different animal tissues, including blood, excreta, and milk. In Study 1,
      treatments consisted of feeding lambs freshly cut Se-enriched canola (containing
      approximately 4 mg Se kg(-1) DM) or control canola (containing <0.1 mg Se kg(-1)
      DM), respectively, for 64 days. In Study 2, treatments consisted of feeding cows
      dried Se-enriched canola (containing approximately 3.5 mg Se kg(-1) DM) as part
      of their daily ration for 20 days. In Study 1 at postmortem, Se concentrations
      were significantly greater in all tested tissues and in excreta from lambs fed Se
      enriched canola. In Study 2, Se values were slightly higher in blood and excreta,
      but not significantly higher in milk from cows sampled throughout the study.
      Significant differences in total live animal weight were not observed between
      treatments in either study. Based on these results, canola plants (not including
      seeds) used for field phytoremediation of Se may be harvested and safely fed to
      lambs and cows to help meet normal Se intake requirements.

PMID- 10903830
TI  - Sublethal copper toxicity and food response in the freshwater crayfish Cambarus
      bartonii (Cambaridae, Decapoda, Crustacea).
AB  - Food response preceding and following exposure to Cu concentrations of 0.00,
      0.02, and 0.2 mg/L was observed in male and female Cambarus bartonii from an
      uncontaminated, freshwater lake. The animals were tested in a Y-maze. Control
      animals demonstrated food localization, and the treated animals, either no
      localization or slight food avoidance. The latency for localization in the Cu
      exposed males increased. Females revealed slight increases in latency. There were
      no significant differences between the low and the high Cu concentration groups
      in food detection or latency. However, there was an increase in mortality in the
      higher concentration group and significant difference in mortality among three
      copper concentrations (P<0.02). Females seem to recover from Cu-induced
      impairment slightly faster than males, suggesting a more efficient mechanism for
      detoxifying copper. Female mortality, however, remained equally high in the high
      Cu concentration group. The toxic effects of copper persist after removal of the
      toxicant and occur at concentrations much lower than reported lethal levels.

PMID- 10903832
TI  - Toxicity of Euphorbia milii latex and niclosamide to snails and nontarget aquatic
      species.
AB  - The toxicity of Euphorbia milii molluscicidal latex and niclosamide (NCL) to
      target snails (Biomphalaria glabrata and Biomphalaria tenagophila) and nontarget
      aquatic organisms is evaluated. Planorbidae snails were killed by very low
      concentrations of lyophilized latex (48-h LC(50), mg/L: B. glabrata, 0.12; B.
      tenagophila, 0.09; Helisoma duryi, 0.10). Latex was less toxic (48-h LC(50) or
      EC(50), mg/L) to oligochaeta (Tubifex tubifex, 0.31), planktonic crustacea
      (Daphnia similis, 0.38; C. dubia, 1.07; Artemia sp., 0.93), and fishes (Danio
      rerio, 0.96; Poecilia reticulata, 1. 39), and considerably less toxic to
      Ampullariidae snails (Pomacea sp. , 10.55) and frog tadpoles (Rana catesbeiana,
      7.50). Latex (up to 100 mg/L) was not toxic to bacteria (P. putida and V.
      fischeri), algae (Selenastrum capricornutum and Chlorella vulgaris), and mosquito
      larvae (Anopheles albitarsis, Aedes aegypti, Aedes fluviatilis). NCL was very
      toxic (48-h LC(50) or EC(50), mg/L) to Planorbidae snails (B. glabrata, 0.15, B.
      tenagophila, 0.13; H. duryi, 0.10), T. tubifex (0.11), crustacea (D. similis,
      0.19; Ceriodaphnia dubia, 0.47; Artemia sp. 0.18), fishes (D. rerio, 0.25; P.
      reticulata, 0.29), R. catesbeiana (0.16), and Pomacea sp. (0.76). NCL was toxic
      to bacteria, algae (96-h IC(50), mg/L: S. capricornutum, 0.34; C. vulgaris, 1.23)
      and slightly toxic to mosquito larvae. In conclusion, E. milii latex, as compared
      with the reference molluscicide niclosamide, presents a higher degree of
      selectivity toward snails which are intermediate hosts of Schistosoma trematodes.

PMID- 10903831
TI  - Disease and gill lesions in yellow perch (Perca flavescens) exposed to oil sands
      mining-associated waters.
AB  - Adult yellow perch were stocked into experimental ponds designed to test the
      biological effects of aquatic reclamation alternatives currently being pursued by
      the oil sands mining industry. Water-quality characteristics of oil sands
      influenced water in the experimental ponds included increased salinity and
      elevated trace organics associated with raw oil sands (bitumen). After 3 and 10
      months of exposure to affected waters, perch gross pathologies including severe
      fin erosion and virally induced tumors were observed in exposed individuals. Gill
      histopathology revealed large aneurysms accompanied by a proliferation of
      chloride and epithelial cells in the interlamellar spaces. Gill pathologies were
      not paralleled by a decrease in plasma sodium, calcium, or chloride. The
      frequencies of gross pathologies and gill changes were correlated to the
      concentrations of the oil sands-related compounds. As inorganic and organic
      compounds associated with oil sands activities are highly intercorrelated, and
      the observed lesions and changes are not diagnostic of particular toxicants, it
      was not possible to isolate the causative chemical factor(s) responsible. The
      incidence of observed lesions and gill pathologies could not be conclusively
      linked to increased mortality rates observed in the exposed populations. Evidence
      of recovery in the pathologies was observed between 3 and 10 months of exposure,
      coincident with a stabilization in population numbers.

PMID- 10903833
TI  - Interacting effects of toxicants and organic matter on the midge Chironomus
      riparius in polluted river water.
AB  - Toxicants and organic matter in river water have contrasting impacts on
      macrofauna. Through manipulations of both factors, their interactive effects on
      organisms were evaluated. This way, an attempt was made to clarify the presence
      or absence of pollution-"tolerant" and -"sensitive" species in rivers affected by
      mixed sources of pollution. Under controlled conditions, larval growth of the
      "tolerant" midge Chironomus riparius was measured in different types of river
      water containing varying levels of particles (obtained by selective filtration)
      and toxicants (either complex mixtures or metals). Exposure of first-instar
      larvae to water from the polluted rivers Meuse and Dommel revealed that growth
      was less inhibited by toxicant levels in river water than expected based on
      laboratory toxicity tests. Factors present in polluted river water stimulated
      growth of midges to such an extent that inhibiting effects of high toxicant
      concentrations were neutralized, and at low toxicant levels, were overcompensated
      for. It was found that particulate matter has great potential to reduce
      inhibiting effects of toxicants on C. riparius, not (only) by reducing the
      bioavailability of toxicants, but by serving as a supplementary, superior food
      source. The success of the "pollution-tolerant" midge was not explained by
      tolerance of this species to toxicants, but by its ability to take advantage of
      coinciding organic enrichment. It is hypothesized that the extent to which
      beneficial effects of organic compounds on organisms occur is species specific.

PMID- 10903835
TI  - Papers to appear in environmental research section A

PMID- 10903834
TI  - Acute toxicity test with Daphnia magna: an alternative to mammals in the
      prescreening of chemical toxicity?
AB  - In this study, the association between the acute toxicity of 15 compounds to
      Daphnia magna, expressed as 24- and 48-h LC(50) values, and the corresponding
      oral LD(50) values for the rat was tested. Since there was evidence of a strong
      relationship between the two species, the sample was extended to 54 cases by
      including the values for acute toxicity to D. magna and rat of more chemicals
      published by other authors. Thus, a total of 54 data points were further used to
      ascertain the relationship between the acute toxicity of chemical compounds to D.
      magna and that to the rat. To summarize its validity, the D. magna test is more
      specific than sensitive as an indicator of toxicity to the rat. When it is used
      with a chemical that has a high probability of being very toxic to D. magna
      (LC(50)< 0.22 mg/L), the test provides considerable information if it is
      positive, virtually giving evidence of toxicity to the rat (with a probability of
      0.83). On the other hand, a negative test (D. magna LC(50)>0.22 mg/L) has a
      probability of correctly assigning nontoxicity to the rat equal to 0.74. This
      study and results published by other authors provide good evidence of the
      applicability of using invertebrate tests as prescreening methods, thus
      considerably reducing the number of mammals required in toxicity testing.

PMID- 10903836
TI  - Construction of a high-resolution physical map of the chromosome 10q22-q23
      dilated cardiomyopathy locus and analysis of candidate genes.
AB  - Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality and a
      leading cause of cardiac transplantation worldwide. Multiple loci and three genes
      encoding cardiac actin, desmin, and lamin A/C have been described for autosomal
      dominant DCM. Using recombination analysis, we have narrowed the 10q21-q23 locus
      to a region of approximately 4.1 cM. In addition, we have constructed a BAC
      contig, composed of 199 clones, which was used to develop a high-resolution
      physical map that contains the DCM critical region (approximately 3.9 Mb long).
      Seven genes, including ANX11, PPIF, DLG5, RPC155, RPS24, SFTPA1, and KCNMA1, have
      been mapped to the region of interest. RPC155, RPS24, SFTPA1, and KCNMA1 were
      excluded from further analysis based on their known functions and tissue-specific
      expression patterns. Mutational analysis of ANX11, DLG5, and PPIF revealed no
      disease-associated mutations. Multiple ESTs have also been mapped to the critical
      region.

PMID- 10903837
TI  - RINX(VSX1), a novel homeobox gene expressed in the inner nuclear layer of the
      adult retina.
AB  - The locus control region (LCR) of the human red and green visual pigment genes is
      critical for the formation of functional red and green cones in the retina. A 37
      bp core of the LCR is perfectly conserved among mammals and binds specific
      retinal nuclear proteins. Here, we employed a yeast one-hybrid screen of an adult
      retinal cDNA library to clone and characterize these proteins. We identified
      clones encoding homeodomain (HD) transcription factors Pax6, Rx, and Chx10 and a
      novel paired-like HD protein, RINX. In the adult retina, RINX is exclusively
      expressed in a subset of cells (likely to be bipolar cells) of the retinal inner
      nuclear layer (INL). RINX is closely related to Chx10, which is also exclusively
      expressed in the INL of the adult retina and is critical for retinal development.
      The RINX gene is expressed in two classes of mRNA. One class encodes proteins
      that lack either part of or all of the HD, but retain the transcriptional
      activation domain. The RINX gene maps to chromosome 20p11.2 to which no retinal
      disease has been assigned. In conclusion, the LCR contains two adjacent motifs
      that are targets for binding of HD proteins that may specify the development and
      differentiation of cone photoreceptors and a subset of INL bipolar cells.
      Mutations in the related human CHX10 gene cause microphthalmia in a subset of
      families, and, therefore, the RINX gene is a candidate for this phenotype in
      another subset of patients. Since the RINX gene is likely an ortholog of the
      goldfish Vsx1 gene, it has been named VSX1 by the Human Gene Nomenclature
      Committee.

PMID- 10903838
TI  - Comparative PCR: a simple and sensitive method for quantifying low-abundance mRNA
      species.
AB  - To measure low-abundance messenger RNA species comparatively, we developed a
      simple and highly sensitive quantification method designated comparative PCR.
      Messenger RNAs from two samples were converted into cDNAs with modified oligo(dT)
      primers (designated RT primers) containing a sample-specific sequence and a
      common sequence. After equal amounts of the cDNAs were mixed together, a target
      gene was amplified by competitive PCR with additional primers: a gene-specific
      primer and a primer consisting of the common sequence of the RT primers. The
      amplified products were visualized by the final PCR, designated fluorescence PCR,
      with an additional three primers: two different fluorescence-labeled primers
      consisting of the sample-specific sequence within the RT primers and a nested
      gene-specific primer. Expression levels of the target gene in the two samples
      were measured by calculating ratios of two different fluorescence intensities. We
      could quantify 0.1-0.3 copies of the target mRNA per cell from only 0.5 ng of
      poly(A)(+) RNA for a single detection. This system should be useful for sensitive
      measurement of scarce transcripts from small samples with a limited amount of RNA
      such as biopsy specimens.

PMID- 10903839
TI  - Identification and characterization of TMEFF2, a novel survival factor for
      hippocampal and mesencephalic neurons.
AB  - We have identified a novel mammalian gene, TMEFF2, that encodes a putative
      transmembrane protein containing two follistatin-like domains and one epidermal
      growth factor (EGF)-like domain. The TMEFF2 gene is predominantly expressed in
      the brain. In situ hybridization analysis revealed that TMEFF2 is widely
      expressed in the brain, including hippocampal cornu ammonis, dentate gyrus, and
      substantia nigra pars compacta. We evaluated the survival effect of TMEFF2 using
      primary cultured neurons from several regions of fetal rat brain following
      treatment with a recombinant TMEFF2 protein fragment consisting of the putative
      extracellular domain. TMEFF2 increased survival of neurons from the hippocampus
      and midbrain, but not from the cerebral cortex, indicating that the survival
      effects of TMEFF2 are specific to certain cell types. Recombinant TMEFF2 also
      promoted survival of mesencephalic dopaminergic neurons. Together, these findings
      suggest that TMEFF2 may be a novel survival factor for hippocampal and
      mesencephalic, but not for cortical, neurons.

PMID- 10903840
TI  - Gene structure and expression of the mouse dyskeratosis congenita gene, dkc1.
AB  - Mutations in the DKC1 gene are responsible for causing X-linked recessive
      dyskeratosis congenita (DKC) and a more severe allelic variant of the disease,
      Hoyeraal-Hreidarsson syndrome. Both diseases are characterized by progressive and
      fatal bone marrow failure. The nucleolar protein dyskerin is the pseudouridine
      synthase component of the box H+ACA snoRNAs and also interacts with the RNA
      component (human telomerase, hTR) of the telomerase complex. Dyskerin is
      therefore thought to function in the processing of pre-rRNA and of the hTR,
      strengthening the notion that the underlying mechanism of DKC is a premature
      senescence of cells, especially of the rapidly dividing epithelial and
      hemopoietic cells. To examine the functions of dyskerin in vivo, it will be
      necessary to generate mouse models. As a first step, we here provide the genomic
      structure of the mouse Dkc1 gene and expression analysis of the transcript.
      Northern hybridizations revealed the tissue-specific expression of an alternative
      4.5-kb transcript, in addition to the ubiquitous 2.6-kb transcript. RNA in situ
      hybridizations on day 10.5-18.5 postconception embryos showed a ubiquitous
      expression of Dkc1 with a notably higher level of expression confined to the
      epithelial tissues. In addition, higher level Dkc1 expression was confined to
      embryonic neural tissues as well as to specific neurons in the cerebellum
      (Purkinje cells) and the olfactory bulb (mitral cells) of the adult brain. In
      adult testis, elevated expression was limited to the Leydig cells. The results
      indicate that some of the pertinent functions of dyskerin may be more tissue
      specific than previously thought and are not limited to rapidly dividing cells.

PMID- 10903841
TI  - The gamma-tubulin gene family in humans.
AB  - Despite the central role of gamma-tubulin in the organization of the microtubule
      cytoskeleton, the gamma-tubulin gene family in humans has not been characterized.
      We now report the identification of a second expressed human gamma-tubulin gene
      (TUBG2) and a gamma-tubulin pseudogene (TUBG1P) in addition to the previously
      identified gamma-tubulin gene (TUBG1). Evidence from Southern hybridizations
      suggests that there are probably no additional gamma-tubulin sequences in the
      human genome. TUBG1 and TUBG2 are within 20 kb of each other in region q21 of
      chromosome 17, and TUBG1P is on chromosome 7. The proteins encoded by TUBG1 and
      TUBG2 share 97.3% amino acid identity, and the two genes are coexpressed in a
      variety of tissues. Previous studies of gamma-tubulin in human tissues and cell
      lines have been based on the tacit assumption that a single gamma-tubulin (the
      gamma-tubulin encoded by TUBG1) was present. While this assumption is not
      correct, the similarity of the products of TUBG1 and TUBG2 suggests that results
      of previous immunolocalization and immunoprecipitation studies in human cells and
      tissues are likely to be valid. In addition, any pharmacological agents that
      target one human gamma-tubulin are likely to target both.

PMID- 10903842
TI  - Identification and molecular characterization of a novel member of the siglec
      family (SIGLEC9).
AB  - Using the positional cloning approach, we have identified siglec-9 (HGMW-approved
      symbol SIGLEC9) a novel member of the sialic acid-binding Ig-like lectin (Siglec)
      family, which belongs to the immunoglobulin superfamily (IgSF). We characterized
      the genomic structure of this gene and determined its chromosomal localization,
      its homology to other members of the siglec family, and its tissue expression
      profile. The siglec-9 gene is composed of seven exons, with six intervening
      introns. The coding region consists of 1392 nucleotides and produces a 463-amino
      acid protein. Furthermore, we have localized this gene to 19q13.4, 43.19 kb more
      telomeric than KLK14 (a member of the kallikrein gene family) through genomic
      sequencing data and restriction mapping with EcoRI. This novel siglec shows a
      high degree of homology to many members of the siglec family, including siglec-7
      (80%), siglec-8 (72%), siglec-5 (65%), and CD33 (64%). This high degree of
      homology is also conserved in the extracellular Ig-like domains. Through RT-PCR,
      we have examined the expression of siglec-9 in a large number of tissues and have
      found relatively high-level expression in bone marrow, placenta, spleen, and
      fetal liver. Based on its homology to CD33, we speculate that this gene may also
      have some utility as a target for immunological antineoplastic therapy.

PMID- 10903843
TI  - Mtr1, a novel biallelically expressed gene in the center of the mouse distal
      chromosome 7 imprinting cluster, is a member of the Trp gene family.
AB  - We recently described a novel putative Ca(2+) channel gene, MTR1, which shows a
      high level of homology to the human TRPC7 gene and the melastatin 1 (MLSN1) gene,
      another Trp (transient receptor potential protein)-related gene whose transcript
      was found to be downregulated in metastatic melanomas. It maps to human
      chromosome band 11p15.5, which is associated with the Beckwith-Wiedemann syndrome
      and predisposition to a variety of neoplasias. Here we report the isolation and
      characterization of the murine orthologue Mtr1. The chromosomal localization on
      distal chromosome 7 places it in a cluster of imprinted genes, flanked by the
      previously described Tapa1 and Kcnq1 genes. The Mtr1 gene encodes a 4.4-kb
      transcript, present in a variety of fetal and adult tissues. The putative open
      reading frame consists of 24 exons, encoding 1158 amino acids. Transmembrane
      prediction algorithms indicate the presence of six membrane-spanning domains in
      the proposed protein. Imprinting analysis, using RT-PCR on RNA from reciprocal
      mouse crosses harboring a sequence polymorphism, revealed biallelic expression of
      Mtr1 transcripts at all stages and tissues examined.

PMID- 10903844
TI  - Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely related to
      CD97.
AB  - The epidermal growth factor (EGF)-TM7 proteins [EMR1, (EGF-like molecule
      containing mucin-like hormone receptor 1) F4/80, and CD97] constitute a recently
      defined class B GPCR subfamily and are predominantly expressed on leukocytes.
      These molecules possess N-terminal EGF-like domains coupled to a seven-span
      transmembrane (7TM) moiety via a mucin-like spacer domain. Genomic mapping
      analysis has suggested a possible EGF-TM7 gene family on the human chromosome
      19p13 region. In this study, a new member of the EGF-TM7 family, EMR2, which
      shares strikingly similar molecular characteristics with CD97, is described. In
      addition to mapping closely to CD97 on human chromosome 19p13.1, EMR2 contains a
      total of five tandem EGF-like domains and expresses similar protein isoforms
      consisting of various numbers of EGF-like domains as a result of alternative RNA
      splicing. Furthermore, EMR2 and CD97 exhibit highly homologous EGF-like domains
      and share identical gene organization, indicating that both genes are the
      products of a recent gene duplication event. The homologous EGF-like domains
      enable the identification of both EMR2 and CD97 by monoclonal antibodies (mAbs)
      raised against the first EGF-like domain of CD97, whereas mAbs directed against
      the extracellular spacer domain of CD97 are able to differentiate these two
      proteins. Both EMR2 and CD97 are highly expressed in immune tissues; however,
      unlike CD97, which is ubiquitously expressed in most cell types, EMR2 expression
      is restricted to monocytes/M&phi; and granulocytes. EMR2 fails to interact with
      CD55, the cellular ligand for CD97, suggesting the possibility of a different
      cellular ligand(s). EMR2 may therefore have a unique function in cells of
      monocyte/M&phi; and granulocyte lineages.

PMID- 10903845
TI  - Multivariate measurement of gene expression relationships.
AB  - The operational activities of cells are based on an awareness of their current
      state, coupled to a programmed response to internal and external cues in a
      context-dependent manner. One key goal of functional genomics is to develop
      analytical methods for delineating the ways in which the individual actions of
      genes are integrated into our understanding of the increasingly complex systems
      of organelle, cell, organ, and organism. This paper describes a novel approach to
      assess the codetermination of gene transcriptional states based upon statistical
      evaluation of reliably informative subsets of data derived from large-scale
      simultaneous gene expression measurements with cDNA microarrays. The method finds
      associations between the expression patterns of individual genes by determining
      whether knowledge of the transcriptional levels of a small gene set can be used
      to predict the associated transcriptional state of another gene. To test this
      approach for identification of the relevant contextual elements of cellular
      response, we have modeled our approach using data from known gene response
      pathways including ionizing radiation and downstream targets of inactivating gene
      mutations. This approach strongly suggests that evaluation of the transcriptional
      status of a given gene(s) can be combined with data from global expression
      analyses to predict the expression level of another gene. With data sets of the
      size currently available, this approach should be useful in finding sets of genes
      that participate in particular biological processes. As larger data sets and more
      computing power become available, the method can be extended to validating and
      ultimately identifying biologic (transcriptional) pathways based upon large-scale
      gene expression analysis.

PMID- 10903846
TI  - Bin2, a functionally nonredundant member of the BAR adaptor gene family.
AB  - BAR family proteins are a unique class of adaptor proteins characterized by a
      common N-terminal fold of undetermined function termed the BAR domain. This set
      of adaptors, which includes the mammalian proteins amphiphysin and Bin1 and the
      yeast proteins Rvs167p and Rvs161p, has been implicated in diverse cellular
      processes, including synaptic vesicle endocytosis, actin regulation,
      differentiation, cell survival, and tumorigenesis. Here we report the
      identification and characterization of Bin2, a novel protein that contains a BAR
      domain but that is otherwise structurally dissimilar to other members of the BAR
      adaptor family. The Bin2 gene is located at chromosome 4q22.1 and is expressed
      predominantly in hematopoietic cells. Bin2 is upregulated during differentiation
      of granulocytes, suggesting that it functions in that lineage. Bin2 formed a
      stable complex in cells with Bin1, but not with amphiphysin, in a BAR domain
      dependent manner. This finding indicates that BAR domains have specific
      preferences for interaction. However, Bin2 did not influence endocytosis in the
      same manner as brain-specific splice isoforms of Bin1, nor did it exhibit the
      tumor suppressor properties inherent to ubiquitous splice isoforms of Bin1. Thus,
      Bin2 appears to encode a nonredundant function in the BAR adaptor gene family.

PMID- 10903847
TI  - Ocat, a paternally expressed gene closely linked and transcribed in the opposite
      direction to Peg3.
AB  - Two reciprocally imprinted Kruppel-type zinc finger genes, Peg3 and Zim1, have
      been found in close proximity on mouse proximal chromosome 7. Here, we describe
      the identification of another novel imprinted transcript, Ocat (ossification
      center-associated transcript). Ocat encodes a 5.5-kb spliced transcript and is
      transcribed in the opposite orientation to Peg3. One of its exons (putative exon
      1) lies approximately 200 bp upstream of Peg3. Ocat is predominantly expressed in
      embryos from days 11 to 17, particularly in ossification centers of the embryonic
      skeleton at day 15. Like Peg3, Ocat is expressed exclusively from the paternal
      allele. Despite their proximity, Peg3 and Ocat showed dissimilar expression
      profiles, suggesting that they are regulated by independent genetic elements.

PMID- 10903848
TI  - An integrated deletion and physical map encompassing l71Rl, a chromosome 7 locus
      required for peri-implantation survival in the mouse.
AB  - l71Rl, a locus that maps just proximal to the pink-eyed dilution (p) locus in
      mouse chromosome 7, was initially identified as being required for early post
      implantation survival. We define further the null phenotype of l71Rl as peri
      implantation lethal, with homozygous mutant embryos degenerating between
      embryonic day 4.5 (E4.5) and E5. 5. We constructed an integrated
      deletion/physical map covering a 1. 82-Mb chromosomal segment extending
      proximally from p. This map defines the minimum critical interval for l71Rl as an
      80- to 300-kb region. This sequence-ready deletion/physical map should enable the
      cloning and characterization of the l71Rl gene(s).

PMID- 10903849
TI  - A 1.5-Mb physical map of the hidrotic ectodermal dysplasia (Clouston syndrome)
      gene region on human chromosome 13q11.
AB  - The HED (hidrotic ectodermal dysplasia) or Clouston syndrome gene (named ED2) has
      been mapped to the pericentromeric region of chromosome 13 (13q11) to a 2.4-cM
      interval flanked by markers D13S1828 and D13S1830. We have developed a BAC/PAC
      based contig map of this region. This contig, comprising 23 clones and spanning
      1.5 Mb, was established by mapping of 27 BAC/PAC end-derived STSs, 11 known
      polymorphic markers, 2 previously mapped genes, and 14 ESTs. The genomic clone
      overlaps were confirmed by restriction fragment fingerprint analysis. This contig
      provides the basis for genomic sequencing and gene identification in the ED2
      critical region. Of the 14 ESTs mapped to the contig, 6 show homology to human
      genes and 8 appear to be novel. Expression patterns of the genes/ESTs were tested
      by Northern blot and RT-PCR. Full characterization of some of these genes, as
      well as the novel ESTs, will be useful in assessing their involvement in the
      HED/Clouston syndrome.

PMID- 10903850
TI  - Transcriptional repressor CopR: the structured acidic C terminus is important for
      protein stability.
AB  - The transcriptional repressor CopR is one of the two copy-number control
      components of plasmid pIP501. CopR binds as a dimer at two consecutive major
      grooves on the same face of the DNA. Previously, equilibrium dissociation
      constants of CopR dimers and the CopR-DNA complex and the intracellular CopR
      concentration were calculated. Amino acid residues involved in DNA binding and
      dimerization were determined. Here, we provide a detailed analysis of the acidic
      C terminus of CopR. A series of C-terminally truncated CopR mutants were analysed
      with regard to activity and half-life in vivo and DNA binding, dimerization,
      structure and stability in vitro. The last 29 amino acid residues of CopR were
      not essential for DNA binding and dimerization but for protein stability.
      However, whereas CopDelta20 was, in spite of drastically shortened half-life,
      still 100 % active in vivo, CopDelta24 and CopDelta27 retained only 20 %
      activity. In vivo stability could be restored only partially by adding a C
      terminal tail previously shown to stabilize the lambda repressor N terminus.
      However, substitution of seven Glu residues by Lys within the last 20 residues
      drastically reduced half-life. Our results clearly demonstrate that the acidic C
      terminus is important for the stability of CopR. Using CD-measurements we show
      that the C terminus of CopR is structured.

PMID- 10903852
TI  - Hydration dynamics of the collagen triple helix by NMR.
AB  - The hydration of the collagen-like Ac-(Gly-Pro-Hyp)(6)-NH(2) triple-helical
      peptide in solution was investigated using an integrated set of high-resolution
      NMR hydration experiments, including different recently developed exchange
      network editing methods. This approach was designed to explore the hydration
      dynamics in the proximity of labile groups, such as the hydroxyproline hydroxyl
      group, and revealed that the first shell of hydration in collagen-like triple
      helices is kinetically labile with upper limits for water molecule residence
      times in the nanosecond to sub-nanosecond range. This result is consistent with a
      "hopping" hydration model in which solvent molecules are exchanged in and out of
      solvation sites at a rate that is not directly correlated to the degree of site
      localization. The hopping model thus reconciles the dynamic view of hydration
      revealed by NMR with the previously suggested partially ordered semi-clathrate
      like cylinder of hydration. In addition, the nanosecond to sub-nanosecond upper
      limits for water molecule residence times imply that hydration-dehydration events
      are not likely to be the rate-limiting step for triple helix self-recognition,
      complementing previous investigations on water dynamics in collagen fibers. This
      study has also revealed labile proton features expected to facilitate the
      characterization of the structure and folding of triple helices in collagen
      peptides.

PMID- 10903851
TI  - The protofilament substructure of amyloid fibrils.
AB  - Tissue deposition of normally soluble proteins, or their fragments, as insoluble
      amyloid fibrils causes the usually fatal, acquired and hereditary systemic
      amyloidoses and is associated with the pathology of Alzheimer's disease, type 2
      diabetes and the transmissible spongiform encephalopathies. Although each type of
      amyloidosis is characterised by a specific amyloid fibril protein, the deposits
      share pathognomonic histochemical properties and the structural morphology of all
      amyloid fibrils is very similar. We have previously demonstrated that
      transthyretin amyloid fibrils contain four constituent protofilaments packed in a
      square array. Here, we have used cross-correlation techniques to average electron
      microscopy images of multiple cross-sections in order to reconstruct the sub
      structure of ex vivo amyloid fibrils composed of amyloid A protein, monoclonal
      immunoglobulin lambda light chain, Leu60Arg variant apolipoprotein AI, and
      Asp67His variant lysozyme, as well as synthetic fibrils derived from a ten
      residue peptide corresponding to the A-strand of transthyretin. All the fibrils
      had an electron-lucent core but the packing arrangement comprised five or six
      protofilaments rather than four. The structural similarity that defines amyloid
      fibres thus exists principally at the level of beta-sheet folding of the
      polypeptides within the protofilament, while the different types vary in the
      supramolecular assembly of their protofilaments.

PMID- 10903853
TI  - PvuII endonuclease contains two calcium ions in active sites.
AB  - Restriction endonucleases differ in their use of metal cofactors despite having
      remarkably similar folds for their catalytic regions. To explore this, we have
      characterized the interaction of endonuclease PvuII with the catalytically
      incompetent cation Ca(2+). The structure of a glutaraldehyde-crosslinked crystal
      of the endonuclease PvuII-DNA complex, determined in the presence of Ca(2+) at a
      pH of approximately 6.5, supports a two-metal mechanism of DNA cleavage by PvuII.
      The first Ca(2+) position matches that found in all structurally examined
      endonucleases, while the second position is similar to that of EcoRV but is
      distinct from that of BamHI and BglI. The location of the second metal in PvuII,
      unlike that in BamHI/BglI, permits no direct interaction between the second metal
      and the O3' oxygen leaving group. However, the interactions between the DNA
      scissile phosphate and the metals, the first metal and the attacking water, and
      the attacking water and DNA are the same in PvuII as they are in the two-metal
      models of BamHI and BglI, but are distinct from the proposed three-metal or the
      two-metal models of EcoRV.

PMID- 10903854
TI  - Mutations induced by bacteriophage T7 RNA polymerase and their effects on the
      composition of the T7 genome.
AB  - We show here that transcription by the bacteriophage T7 RNA polymerase increases
      the deamination of cytosine bases in the non-transcribed strand to uracil,
      causing C to T mutations in that strand. Under optimal conditions, the mutation
      frequency increases about fivefold over background, and is similar to that seen
      with the Escherichia coli RNA polymerase. Further, we found that a mutant T7 RNA
      polymerase with a slower rate of elongation caused more cytosine deaminations
      than its wild-type parent. These results suggest that promoting cytosine
      deamination in the non-transcribed strand is a general property of transcription
      in E. coli and is dependent on the length of time the transcription bubble stays
      open during elongation. To see if transcription-induced mutations have influenced
      the evolution of bacteriophage T7, we analyzed its genome for a bias in base
      composition. Our analysis showed a significant excess of thymine over cytosine
      bases in the highly transcribed regions of the genome. Moreover, the average
      value of this bias correlated well with the levels of transcription of different
      genomic regions. Our results indicate that transcription-induced mutations have
      altered the composition of bacteriophage T7 genome and suggest that this may be a
      significant force in genome evolution.

PMID- 10903855
TI  - Recognition of oriT for DNA processing at termination of a round of conjugal
      transfer.
AB  - Conjugal transfer of plasmid DNA is terminated when the transferred strand,
      linearized at the 38 base-pair origin of transfer (oriT), is recircularized. For
      the plasmid R1162, it is the protein MobA, covalently linked to the linear
      strand, that rejoins the ends by a reversible transesterification reaction. We
      have identified from those oligonucleotides with a partially degenerate oriT base
      sequence, subpopulations bound by MobA that undergo transesterification, and
      support efficient termination of conjugal transfer. Two domains of oriT, a ten
      base-pair inverted repeat and an adjacent TAA, are required for tight binding by
      the protein, whereas the location of the dinucleotide YG determines the site of
      strand cleavage. The results indicate that capture of MobA by oriT, and
      subsequent processing of the DNA for termination, are determined by different
      sequence motifs within this locus.

PMID- 10903856
TI  - Multiple regulators and their interactions in vivo and in vitro with the cbb
      regulons of Rhodobacter capsulatus.
AB  - The cbb(I) and cbb(II) operons encode structural genes which are important for
      carbon dioxide fixation via the Calvin-Benson-Bassham reductive pentose phosphate
      pathway in Rhodobacter capsulatus. Each operon is regulated by cognate LysR-type
      transcriptional activators, CbbR(I) and CbbR(II), with the product of the cbbR(I)
      gene, CbbR(I), able to control its own transcription under some growth
      conditions. Furthermore, CbbR(I) may at least partially regulate the cbb(II)
      operon, with significant, yet regulated transcription of the cbb(II) operon
      occurring in the absence of any CbbR. These results suggested the importance of
      additional regulators. Thus, in addition to the rather specific control exerted
      by CbbR, a more globally significant regulatory system, the RegA-RegB (PrrA-PrrB)
      two-component system, was found to contribute to transcriptional regulation of
      each cbb operon. The regA and regB mutant strains were found to contain
      constitutive levels of form I and form II RubisCO, the major proteins encoded by
      the cbb(I) and cbb(II) operons, respectively. In addition, DNaseI footprint
      analyses indicated that RegA*, a constitutively active mutant form of RegA, binds
      specifically to cbb(I) and cbb(II) promoter-operator regions. CbbR(I), CbbR(II),
      and RegA binding loci were localized relative to transcription start sites,
      leading to a coherent picture of how each of these regulators interacts with
      specific promoter-operator sequences of the cbb operons.

PMID- 10903858
TI  - Water and ion binding around RNA and DNA (C,G) oligomers.
AB  - The dynamics, hydration, and ion-binding features of two duplexes, the
      A(r(CG)(12)) and the B(d(CG)(12)), in a neutralizing aqueous environment with
      0.25 M added KCl have been investigated by molecular dynamics (MD) simulations.
      The regular repeats of the same C=G base-pair motif have been exploited as a
      statistical alternative to long MD simulations in order to extend the sampling of
      the conformational space. The trajectories demonstrate the larger flexibility of
      DNA compared to RNA helices. This flexibility results in less well defined
      hydration patterns around the DNA than around the RNA backbone atoms. Yet, 22
      hydration sites are clearly characterized around both nucleic acid structures.
      With additional results from MD simulations, the following hydration scale for
      C=G pairs can be deduced: A-DNA<RNA (+3 H(2)O) and B-DNA<RNA (+2 H(2)O). The
      calculated residence times of water molecules in the first hydration shell of the
      helices range from 0.5 to 1 ns, in good agreement with available experimental
      data. Such water molecules are essentially found in the vicinity of the phosphate
      groups and in the DNA minor groove. The calculated number of ions that break into
      the first hydration shell of the nucleic acids is close to 0.5 per base-pair for
      both RNA and DNA. These ions form contacts essentially with the oxygen atoms of
      the phosphate groups and with the guanine N7 and O6 atoms; they display residence
      times in the deep/major groove approaching 500 ps. Further, a significant
      sequence-dependent effect on ion binding has been noted. Despite slight
      structural differences, K(+) binds essentially to GpC and not to CpG steps. These
      results may be of importance for understanding various sequence-dependent binding
      affinities. Additionally, the data help to rationalize the experimentally
      observed differences in gel electrophoretic mobility between RNA and DNA as due
      to the difference in hydration (two water molecules in favor of RNA) rather than
      to strong ion-binding features, which are largely similar for both nucleic acid
      structures.

PMID- 10903857
TI  - fhlA repression by OxyS RNA: kissing complex formation at two sites results in a
      stable antisense-target RNA complex.
AB  - OxyS is a small untranslated RNA that is induced in response to oxidative stress
      in Escherichia coli. This small RNA acts as a global regulator affecting the
      expression of multiple genes. OxyS represses the translation of fhlA, a
      transcriptional activator for formate metabolism. Previously, we have shown that
      fhlA repression by OxyS is mediated through base-pairing with a short sequence
      overlapping the ribosome binding site. Here we show that the OxyS-fhlA
      interaction involves a second site residing further downstream, within the coding
      region of fhlA. Mutations that disrupt pairing at this site affect the ability of
      OxyS to prevent 30 S ribosomes from binding to fhlA mRNA. Structure probing of
      fhlA mRNA demonstrates that both sites reside in the loops of two stem-loop
      structures. OxyS-fhlA pairing analysis shows that OxyS binds wild-type fhlA with
      an apparent dissociation constant of 25 nM, indicating that kissing complex
      formation between OxyS and fhlA results in a stable antisense-target complex.
      Mutations at either site, which disrupt pairing of OxyS to fhlA, decrease the
      stability of this complex. Our results indicate that kissing complex formation is
      sufficient to repress fhlA translation by OxyS.

PMID- 10903859
TI  - Replication fork density increases during DNA synthesis in X. laevis egg
      extracts.
AB  - Duplication of the eukaryotic genome depends on the temporal and spatial
      organization of DNA replication during the cell cycle. To investigate the genomic
      organization of DNA replication in a higher eukaryote, multiple origins of
      replication must be simultaneously analyzed over large regions of the genome as
      DNA synthesis progresses through S phase of the cell cycle. We have employed a
      novel technique that allows for the quantitative analysis of DNA replication on a
      genome wide basis. The technique involves stretching and aligning individual DNA
      molecules on a glass surface. As a model system, Xenopus laevis egg extract was
      used to differentially label sperm chromatin at successive time points after the
      start of DNA synthesis. The differentially labeled DNA allows earlier and later
      replicating sequences to be distinguished, and hence the sites of DNA synthesis
      at any given time can be directly visualized. Genomic DNA was extracted, and
      measurements made on the linearized molecules provided a comprehensive analysis
      of the spatial and temporal organization of DNA replication in the X. laevis in
      vitro replication system. It was found that: (i) DNA synthesis initiates
      asynchronously at irregular intervals but continuously as DNA replication
      advances; and (ii) that the frequency of initiation (the number of activated
      origins per kilobase) increases as DNA synthesis nears completion. The
      implications of these findings for the regulation of DNA replication in early
      embryos is discussed.

PMID- 10903860
TI  - Solution conformation of a bulged adenosine base in an RNA duplex by relaxation
      matrix refinement.
AB  - Bulges are common structural motifs in RNA secondary structure and are thought to
      play important roles in RNA-protein and RNA-drug interactions. Adenosine bases
      are the most commonly occurring unpaired base in double helical RNA secondary
      structures. The solution conformation and dynamics of a 25-nucleotide RNA duplex
      containing an unpaired adenosine, r(GGCAGAGUGCCGC): r(GCGGCACCUGCC) have been
      studied by NMR spectroscopy and MORASS iterative relaxation matrix structural
      refinement. The results show that the bulged adenosine residue stacks into the
      RNA duplex with little perturbation around the bulged region. Most of the bases
      in the RNA duplex adopt C(3)'-endo conformation, exhibiting the N-type sugar
      pucker as found in the A form helices. The sugars of the bulged residue and the
      5' flanking residue to it are found to exhibit C(2)'-endo conformation. None of
      the residues are in syn conformation.

PMID- 10903861
TI  - Human genome search in celiac disease using gliadin cDNA as probe.
AB  - Celiac disease is a wheat gliadin-promoted disorder that displays a complex
      genetic susceptibility associated with HLA-DQ2, and one or more unknown
      factor(s), possibly gliadin-like. The presence of mammalian proteins with partial
      gliadin similarity was suggested by transglutaminase-independent multi-tissue
      reactivity of gliadin-immunopurified antibodies from celiac patients. No non
      plant sequence, however, was identified in gliadin peptide epitope searches of
      non-redundant and EST databanks via TBLASTN, BLASTP and FASTA, even at E values
      as high as 20. Therefore, an alpha-gliadin cDNA screen of human cDNA and genomic
      libraries was undertaken, an approach in keeping with positive human Northern and
      Southern analyses with the same probe. Four distinct cDNA clones were obtained,
      the most stringent of which (3.2 and 5.1 kb) were novel, and featured potential
      open reading frames with high gliadin domain II and domain IV homologies (BestFit
      quality scores >/=295 and 322, respectively, versus random value 126-127). Both
      were also homologous to ESTs. An additional 5' gliadin oligonucleotide screen
      identified the widely distributed cytoplasmic protein acyl coA hydrolase whose
      homology was restricted to the oligonucleotide probe (BestFit quality=215 versus
      100 for random); and achaete-scute homologous protein, which displays
      particularly high gliadin domain II homology (BestFit quality 316 versus 111 for
      random). Genomic screening uncovered 16 positives, one of which was the ALR gene,
      whose similarity to three of gliadin's five domains (I, II and IV; BestFit
      quality 322-473 versus 121-154 for random) was remarkable. More extensive was
      novel genomic clone 2, with fragments hybridizing to cDNA probes approximating
      gliadin domains I, II+IV, V and the gliadin 5' untranslated region, and mapping
      by FISH to 19q13.11-13. 12. Two fragments were sequenced; one was exonic, as
      predicted by four different programs; and test oligonucleotides suggested
      widespread 4 and/or 2 kb mRNA expression, even at high stringency (t(m)-8.8 deg.
      C). Taken together, it is apparent that several genes with partial gliadin
      homology exist in the human genome. Many bear gliadin-like T-cell epitopes, are
      expressed in intestine and, like transglutaminase, are cytoplasmic. Glutamine to
      glutamic acid or other mutation within such epitopes followed by injury or
      infection-related release could explain enhanced disease susceptibility in
      affected families.

PMID- 10903862
TI  - Electron microscopy and subunit-subunit interaction studies reveal a first
      architecture of COP9 signalosome.
AB  - The COP9 signalosome is involved in signal transduction, whereas the 26 S
      proteasome lid is a regulatory subcomplex of the 26 S proteasome responsible for
      degradation of ubiquitinated proteins. COP9 signalosome and lid possess
      significant sequence homologies among their eight core subunits and are likely
      derived from a common ancestor. Surprisingly, from our two-dimensional electron
      microscopy data, a common architectural plan for the two complexes could not be
      deduced. None-the-less, the two particles have structural features in common.
      Both COP9 signalosome and lid lack any symmetry in subunit arrangement and
      exhibit a central groove, possibly qualified for scaffolding functions.Filter
      binding assays with recombinant COP9 signalosome components revealed a multitude
      of subunit-subunit interactions, supporting the asymmetrical appearance of the
      complex in electron microscopy. On the basis of two-dimensional images and
      subunit interaction studies, a first architectural model of COP9 signalosome was
      created. The fact that four distinct classes of particle views were identified
      and that only 50 % of the selected particles could be classified indicates a high
      degree of heterogeneity in electron microscopic images. Different orientations
      with respect to the viewing axis and conformational variety, presumably due to
      different grades of phosphorylation, are possible reasons for the heterogeneous
      appearance of the complex. Our biochemical data show that recombinant COP9
      signalosome subunits 2 and 7 are phosphorylated by the associated kinase
      activity. The modification of COP9 signalosome subunit 2 might be essential for c
      Jun phosphorylation. Dephosphorylation does not inactivate the associated kinase
      activity. Although substrate phosphorylation by COP9 signalosome is significantly
      decreased by lambda protein phosphatase treatment, "autophosphorylation" is
      increased.

PMID- 10903863
TI  - Structure of human rhinovirus serotype 2 (HRV2).
AB  - Human rhinoviruses are classified into a major and a minor group based on their
      binding to ICAM-1 or to members of the LDL-receptor family, respectively. They
      can also be divided into groups A and B, according to their sensitivity towards a
      panel of antiviral compounds. The structure of human rhinovirus 2 (HRV2), which
      uses the LDL receptor for cell attachment and is included in antiviral group B,
      has been solved and refined at 2.6 A resolution by X-ray crystallography to gain
      information on the peculiarities of rhinoviruses, in particular from the minor
      receptor group. The main structural differences between HRV2 and other
      rhinoviruses, including the minor receptor group serotype HRV1A, are located at
      the internal protein shell surface and at the external antigenic sites. In the
      interior, the N termini of VP1 and VP4 form a three-stranded beta-sheet in an
      arrangement similar to that present in poliovirus, although myristate was not
      visible at the amino terminus of VP4 in the HRV2 structure. The betaE-betaF loop
      of VP2, a linear epitope within antigenic site B recognized by monoclonal
      antibody 8F5, adopts a conformation considerably different from that found in the
      complex of 8F5 with a synthetic peptide of the same sequence. This either points
      to considerable structural changes impinged on this loop upon antibody binding,
      or to the existence of more than one single conformation of the loop when the
      virus is in solution. The hydrophobic pocket of VP1 was found to be occupied by a
      pocket factor apparently identical with that present in the major receptor group
      virus HRV16. Electron density, consistent with the presence of a viral RNA
      fragment, is seen stacked against a conserved tryptophan residue.

PMID- 10903864
TI  - The structural basis for in situ activation of DNA alkylation by duocarmycin SA.
AB  - Duocarmycin SA is a member of a growing class of interesting lead compounds for
      chemotherapy, distinguished by the manner in which they bind to and react with
      DNA substrates. The first three-dimensional structure of a DNA adduct of an
      unnatural enantiomer from this family has been determined by (1)H NMR methods.
      Comparison to the previously determined structure of the natural enantiomer bound
      in the same DNA-binding site provides unique insights into the similarities and
      critical distinctions producing the respective alkylation products and site
      selectivities. The results also support the hypothesis that the duocarmycin SA
      alkylation reaction is catalyzed by the binding to DNA, and provide a deeper
      understanding of the structural basis for this unique mode of activation.

PMID- 10903865
TI  - Modeling of the TCR-MHC-peptide complex.
AB  - The methodology for generating a homology model of the T1 TCR-PbCS-K(d) class I
      major histocompatibility complex (MHC) class I complex is presented. The
      resulting model provides a qualitative explanation of the effect of over 50
      different mutations in the region of the complementarity determining region (CDR)
      loops of the T cell receptor (TCR), the peptide and the MHC's alpha(1)/alpha(2)
      helices. The peptide is modified by an azido benzoic acid photoreactive group,
      which is part of the epitope recognized by the TCR. The construction of the model
      makes use of closely related homologs (the A6 TCR-Tax-HLA A2 complex, the 2C TCR,
      the 14.3.d TCR Vbeta chain, the 1934.4 TCR Valpha chain, and the H-2 K(b)
      ovalbumine peptide), ab initio sampling of CDR loops conformations and
      experimental data to select from the set of possibilities. The model shows a
      complex arrangement of the CDR3alpha, CDR1beta, CDR2beta and CDR3beta loops that
      leads to the highly specific recognition of the photoreactive group. The protocol
      can be applied systematically to a series of related sequences, permitting the
      analysis at the structural level of the large TCR repertoire specific for a given
      peptide-MHC complex.

PMID- 10903866
TI  - Coupling photoisomerization of retinal to directional transport in
      bacteriorhodopsin.
AB  - In order to understand how isomerization of the retinal drives unidirectional
      transmembrane ion transport in bacteriorhodopsin, we determined the atomic
      structures of the BR state and M photointermediate of the E204Q mutant, to 1.7
      and 1.8 A resolution, respectively. Comparison of this M, in which proton release
      to the extracellular surface is blocked, with the previously determined M in the
      D96N mutant indicates that the changes in the extracellular region are initiated
      by changes in the electrostatic interactions of the retinal Schiff base with
      Asp85 and Asp212, but those on the cytoplasmic side originate from steric
      conflict of the 13-methyl retinal group with Trp182 and distortion of the pi
      bulge of helix G. The structural changes suggest that protonation of Asp85
      initiates a cascade of atomic displacements in the extracellular region that
      cause release of a proton to the surface. The progressive relaxation of the
      strained 13-cis retinal chain with deprotonated Schiff base, in turn, initiates
      atomic displacements in the cytoplasmic region that cause the intercalation of a
      hydrogen-bonded water molecule between Thr46 and Asp96. This accounts for the
      lowering of the pK(a) of Asp96, which then reprotonates the Schiff base via a
      newly formed chain of water molecules that is extending toward the Schiff base.

PMID- 10903867
TI  - Tyr115, gln165 and trp209 contribute to the 1, 2-epoxy-3-(p-nitrophenoxy)propane
      conjugating activity of glutathione S-transferase cGSTM1-1.
AB  - We investigated the epoxidase activity of a class mu glutathione S-transferase
      (cGSTM1-1), using 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) as substrate. Trp209
      on the C-terminal tail, Arg107 on the alpha4 helix, Asp161 and Gln165 on the
      alpha6 helix of cGSTM1-1 were selected for mutagenesis and kinetic studies. A
      hydrophobic side-chain at residue 209 is needed for the epoxidase activity of
      cGSTM1-1. Replacing Trp209 with histidine, isoleucine or proline resulted in a
      fivefold to 28-fold decrease in the k(cat)(app) of the enzyme, while a modest 25
      % decrease in the k(cat)(app) was observed for the W209F mutant. The rGSTM1-1
      enzyme has serine at the correponding position. The k(cat)(app) of the S209W
      mutant is 2. 5-fold higher than that of the wild-type rGSTM1-1. A charged residue
      is needed at position 107 of cGSTM1-1. The K(m)(app)(GSH) of the R107L mutant is
      38-fold lower than that of the wild-type enzyme. On the contrary, the R107E
      mutant has a K(m)(app)(GSH) and a k(cat)(app) that are 11-fold and 35 % lower
      than those of the wild-type cGSTM1-1. The substitutions of Gln165 with Glu or Leu
      have minimal effect on the affinity of the mutants towards GSH or EPNP. However,
      a discernible reduction in k(cat)(app) was observed. Asp161 is involved in
      maintaining the structural integrity of the enzyme. The K(m)(app)(GSH) of the
      D161L mutant is 616-fold higher than that of the wild-type enzyme. In the
      hydrogen/deuterium exchange experiments, this mutant has the highest level of
      deuteration among all the proteins tested. We also elucidated the structure of
      cGSTM1-1 co-crystallized with the glutathionyl-conjugated 1, 2-epoxy-3-(p
      nitrophenoxy)propane (EPNP) at 2.8 A resolution. The product found in the active
      site was 1-hydroxy-2-(S-glutathionyl)-3-(p-nitrophenoxy)propane, instead of the
      conventional 2-hydroxy isomer. The EPNP moiety orients towards Arg107 and Gln165
      in dimer AB, and protrudes into a hydrophobic region formed by the loop
      connecting beta1 and alpha1 and part of the C-terminal tail in dimer CD. The
      phenoxyl ring forms strong ring stacking with the Trp209 side-chain in dimer CD.
      We hypothesize that these two conformations represent the EPNP moiety close to
      the initial and final stages of the reaction mechanism, respectively.

PMID- 10903868
TI  - Crystal structure of human grancalcin, a member of the penta-EF-hand protein
      family.
AB  - Grancalcin is a Ca(2+)-binding protein expressed at high level in neutrophils. It
      belongs to the PEF family, proteins containing five EF-hand motifs and which are
      known to associate with membranes in Ca(2+)-dependent manner. Prototypic members
      of this family are Ca(2+)-binding domains of calpain. Our recent finding that
      grancalcin interacts with L-plastin, a protein known to have actin bundling
      activity, suggests that grancalcin may play a role in regulation of adherence and
      migration of neutrophils. The structure of human grancalcin has been determined
      at 1.9 A resolution in the absence of calcium (R-factor of 0.212 and R-free of
      0.249) and at 2. 5 A resolution in the presence of calcium (R-factor of 0.226 and
      R-free of 0.281). The molecule is predominantly alpha-helical: it contains eight
      alpha-helices and only two short stretches of two-stranded beta-sheets between
      the loops of paired EF-hands. Grancalcin forms dimers through the association of
      the unpaired EF5 hands in a manner similar to that observed in calpain,
      confirming this mode of association as a paradigm for the PEF family. Only one
      Ca(2+) was found per dimer under crystallization conditions that included
      CaCl(2). This cation binds to EF3 in one molecule, while this site in the second
      molecule of the dimer is unoccupied. This unoccupied site shows higher mobility.
      The structure determined in the presence of calcium, although does not represent
      a fully Ca(2+)-loaded form, suggests that calcium induces rather small
      conformational rearrangements. Comparison with calpain suggests further that the
      relatively small magnitude of conformational changes invoked by calcium alone may
      be a characteristic feature of the PEF family. Moreover, the largest differences
      are localized to the EF1, thus supporting the notion that calcium signaling
      occurs through this portion of the molecule and that it may involve the N
      terminal Gly/Pro rich segment. Electrostatic potential distribution shows
      significant differences between grancalcin and calpain domain VI demonstrating
      their distinct character.

PMID- 10903869
TI  - Structural changes in a hydrophobic domain of the prion protein induced by
      hydration and by ala-->Val and pro-->Leu substitutions.
AB  - X-ray diffraction was used to study the structure of assemblies formed by
      synthetic peptide fragments of the prion protein (PrP) that include the
      hydrophobic domain implicated in the Gerstmann-Straussler-Scheinker (GSS)
      mutation (P102L). The effects of hydration on polypeptide assembly and of Ala-
      >Val substitutions in the hydrophobic domain were characterized. Synthetic
      peptides included: (i) Syrian hamster (SHa) hydrophobic core, SHa106-122
      (KTNMKHMAGAAAAGAVV); (ii) SHa104-122(3A-V), with A-->V mutations at 113, 115 and
      118 (KPKTNMKHMVGVAAVGAVV); (iii) mouse (Mo) wild-type sequence of the N-terminal
      hydrophobic domain, Mo89-143WT; and (iv) the same mouse sequence with leucine
      substitution for proline at residue number 101, Mo89-143(P101L). Samples of
      SHa106-122 that formed assemblies while drying under ambient conditions showed X
      ray patterns indicative of 33 A thick slab-like structures having extensive H
      bonding and intersheet stacking. By contrast, lyophilized peptide that was
      equilibrated against 100 % relative humidity showed assemblies with only a few
      layers of beta-sheets. The Ala-->Val substitutions in SHa104-122 and Mo89
      143(P101L) resulted in the formation of 40 A wide, cross-beta fibrils.
      Observation of similar size beta-sheet fibrils formed by peptides SHa104-122(3A
      V) and the longer Mo89-143(P101L) supports the notion that the hydrophobic
      sequence forms a template or core that promotes the beta-folding of the longer
      peptide. The substitution of amino acids in the mutants, e.g. 3A-->V and P101L,
      enhances the folding of the peptide into compact structural units, significantly
      enhancing the formation of the extensive beta-sheet fibrils.

PMID- 10903870
TI  - Three-dimensional crystal structure of human eosinophil cationic protein (RNase
      3) at 1.75 A resolution.
AB  - Eosinophil cationic protein (ECP; RNase 3) is a human ribonuclease found only in
      eosinophil leukocytes that belongs to the RNase A superfamily. This enzyme is
      bactericidal, helminthotoxic and cytotoxic to mammalian cells and tissues. The
      protein has been cloned, heterologously overexpressed, purified and crystallized.
      Its crystal structure has been determined and refined using data up to 1. 75 A
      resolution. The molecule displays the alpha+beta folding topology typical for
      members of the ribonuclease A superfamily. The catalytic active site residues are
      conserved with respect to other ribonucleases of the superfamily but some
      differences appear at substrate recognition subsites, which may account, in part,
      for the low catalytic activity. Most strikingly, 19 surface-located arginine
      residues confer a strong basic character to the protein. The high concentration
      of positive charges and the particular orientation of the side-chains of these
      residues may also be related to the low activity of ECP as a ribonuclease and
      provides an explanation for its unique cytotoxic role through cell membrane
      disruption.

PMID- 10903871
TI  - Tetracycline affects abnormal properties of synthetic PrP peptides and PrP(Sc) in
      vitro.
AB  - Prion diseases are characterized by the accumulation of altered forms of the
      prion protein (termed PrP(Sc)) in the brain. Unlike the normal protein, PrP(Sc)
      isoforms have a high content of beta-sheet secondary structure, are protease
      resistant, and form insoluble aggregates and amyloid fibrils. Evidence indicates
      that they are responsible for neuropathological changes (i.e. nerve cell
      degeneration and glial cell activation) and transmissibility of the disease
      process. Here, we show that the antibiotic tetracycline: (i) binds to amyloid
      fibrils generated by synthetic peptides corresponding to residues 106-126 and 82
      146 of human PrP; (ii) hinders assembly of these peptides into amyloid fibrils;
      (iii) reverts the protease resistance of PrP peptide aggregates and PrP(Sc)
      extracted from brain tissue of patients with Creutzfeldt-Jakob disease; (iv)
      prevents neuronal death and astrocyte proliferation induced by PrP peptides in
      vitro. NMR spectroscopy revealed several through-space interactions between
      aromatic protons of tetracycline and side-chain protons of Ala(117-119), Val(121
      122) and Leu(125) of PrP 106-126. These properties make tetracycline a prototype
      of compounds with the potential of inactivating the pathogenic forms of PrP.

PMID- 10903872
TI  - Mutational analysis and NMR studies of the death domain of the tumor necrosis
      factor receptor-1.
AB  - Tumor necrosis factor receptor-1 (TNFR-1) death domain (DD) is the intracellular
      functional domain responsible for the receptor signaling activities. To
      understand the transduction mechanism of TNFR-1 signaling we performed structural
      and functional analysis of the TNFR-DD. The secondary structure of the TNFR-DD
      shows that it consists of six anti-parallel alpha-helices. The determination of
      the topological fold and an extensive mutagenesis analysis revealed that there
      are two opposite faces that are involved in self-association and interaction with
      the TRADD death domain. Interestingly, the same critical residues in TNFR-DD are
      involved in both interactions. There is a good correlation between the binding
      activities of the mutant proteins and their cytotoxic activities. These results
      provide important insight into the molecular interactions mediating TNFR-DD self
      association and subsequent recruitment of TRADD in the signaling activity of TNFR
      1.

PMID- 10903873
TI  - Amino acid conformational preferences and solvation of polar backbone atoms in
      peptides and proteins.
AB  - Amino acids in peptides and proteins display distinct preferences for alpha
      helical, beta-strand, and other conformational states. Various physicochemical
      reasons for these preferences have been suggested: conformational entropy, steric
      factors, hydrophobic effect, and backbone electrostatics; however, the issue
      remains controversial. It has been proposed recently that the side-chain
      dependent solvent screening of the local and non-local backbone electrostatic
      interactions primarily determines the preferences not only for the alpha-helical
      but also for all other main-chain conformational states. Side-chains modulate the
      electrostatic screening of backbone interactions by excluding the solvent from
      the vicinity of main-chain polar atoms. The deficiency of this electrostatic
      screening model of amino acid preferences is that the relationships between the
      main-chain electrostatics and the amino acid preferences have been demonstrated
      for a limited set of six non-polar amino acid types in proteins only. Here, these
      relationships are determined for all amino acid types in tripeptides,
      dekapeptides, and proteins. The solvation free energies of polar backbone atoms
      are approximated by the electrostatic contributions calculated by the finite
      difference Poisson-Boltzmann and the Langevin dipoles methods. The results show
      that the average solvation free energy of main-chain polar atoms depends strongly
      on backbone conformation, shape of side-chains, and exposure to solvent. The
      equilibrium between the low-energy beta-strand conformation of an amino acid
      (anti-parallel alignment of backbone dipole moments) and the high-energy alpha
      conformation (parallel alignment of backbone dipole moments) is strongly
      influenced by the solvation of backbone polar atoms. The free energy cost of
      reaching the alpha conformation is by approximately 1.5 kcal/mol smaller for
      residues with short side-chains than it is for the large beta-branched amino acid
      residues. This free energy difference is comparable to those obtained
      experimentally by mutation studies and is thus large enough to account for the
      distinct preferences of amino acid residues. The screening coefficients
      gamma(local)(r) and gamma(non-local)(r) correlate with the solvation effects for
      19 amino acid types with the coefficients between 0.698 to 0.851, depending on
      the type of calculation and on the set of point atomic charges used. The
      screening coefficients gamma(local)(r) increase with the level of burial of amino
      acids in proteins, converging to 1.0 for the completely buried amino acid
      residues. The backbone solvation free energies of amino acid residues involved in
      strong hydrogen bonding (for example: in the middle of an alpha-helix) are small.
      The hydrogen bonded backbone is thus more hydrophobic than the peptide groups in
      random coil. The alpha-helix forming preference of alanine is attributed to the
      relatively small free energy cost of reaching the high-energy alpha-helix
      conformation. These results confirm that the side-chain-dependent solvent
      screening of the backbone electrostatic interactions is the dominant factor in
      determining amino acid conformational preferences.

PMID- 10903874
TI  - A statistical appraisal of native state hydrogen exchange data: evidence for a
      burst phase continuum?
AB  - For a number of proteins, folding occurs via the rapid accumulation of secondary
      and tertiary structural features in a so-called burst phase, preceding the
      relatively slow, highly activated transition leading to the native state. A
      fundamental question is: do these burst phase reactions comprise two phase
      separated thermodynamic states or a continuum of states? Ribonuclease HI (RNase
      H) from Escherichia coli and phage T4 lysozyme (T4L) both exhibit such a
      phenomenon. Native-state hydrogen exchange (NHX) data have been collected for
      these proteins, providing residue-specific free energies and m-values (a measure
      of hydrocarbon solvation) for the manifold of partially unfolded, exchange
      competent forms that are accessible from the native state (DeltaG(sg) and m(sg),
      where the sg subscript denotes sub-global). There is good evidence that these
      parameters pertain to exchange-competent species comprising the burst phase
      observed in the global folding kinetics. We combine the results from the global
      folding kinetics of these proteins with a statistical analysis of their NHX
      parameters to determine if the distribution of experimental (m(sg), DeltaG(sg))
      values derive from a mechanism where the burst phase is two-state. For RNase H,
      this analysis demonstrates that the burst phase of this protein is not two-state;
      the results imply a distribution of states, m and DeltaG exhibiting a linear
      functional relationship consistent with the global folding parameters. For T4L,
      it is difficult to distinguish the observed distribution of m(sg), DeltaG(sg)
      values from that expected for a mechanism where the burst phase is two-state. The
      results for RNase H* lend support for the idea that the burst phase reaction of
      this protein comprises a continuum of states. This has important implications for
      how we model the process of structural acquisition in protein folding reactions.

PMID- 10903875
TI  - The contribution of buried polar groups to the conformational stability of the
      GCN4 coiled coil.
AB  - The dimeric interface of the leucine zipper coiled coil from GCN4 has been used
      to probe the contributions of hydrophobic and hydrogen bonding interactions to
      protein stability. We have determined the energetics of placing Ile or Asn
      residues at four buried positions in a two-stranded coiled coil. As expected, Ile
      is favored over Asn at these buried positions, but not as much as predicted by
      considering only the hydrophobic effect. It appears that interstrand hydrogen
      bonds form between the side-chains of the buried Asn residues and these
      contribute to the conformational stability of the coiled-coil peptides. However,
      these contributions are highly dependent on the locations of the Asn pairs. The
      effect of an Ile to Asn mutation is greatest at the N terminus of the peptide and
      decreases almost twofold as we move the substitution from the N to C-terminal
      heptads.

PMID- 10903876
TI  - Interspecies hybrid HbS: complete neutralization of Val6(beta)-dependent
      polymerization of human beta-chain by pig alpha-chains.
AB  - Interspecies hybrid HbS (alpha(2)(P)beta(2)(S)), has been assembled in vitro from
      pig alpha-globin and human beta(S)-chain. The alpha(2)(P)beta(2)(S) retains
      normal tetrameric structure (alpha(2)beta(2)) of human Hb and an O(2) affinity
      comparable to that of HbS in 50 mM Hepes buffer; but, its O(2) affinity is
      slightly higher than that of HbS in the presence of allosteric effectors
      (chloride, DPG and phosphate). The (1)H-NMR spectroscopy detected distinct
      differences between the heme environments and alpha(1)beta(1) interfaces of pig
      Hb and HbS, while their alpha(1)beta(2) interfaces appear very similar. The
      interspecies hybrid alpha(2)(H)beta(2)(P) resembles pig Hb; the pig beta-chain
      dictated the conformation of the heme environment of the human alpha-subunit, and
      to the alpha(1)beta(1) interfaces of the hybrid. In the alpha(2)(P)beta(2)(S)
      hybrid, beta(S)-chain dictated the conformation of human heme environment to the
      pig alpha-chain in the hybrid; but the conformation of alpha(1)beta(1) interface
      of this hybrid is close to, but not identical to that of HbS. On the other hand,
      the alpha(1)beta(2) interface conformation is identical to that of HbS. More
      important, the alpha(2)(P)beta(2)(S) does not polymerize when deoxygenated; pig
      alpha-chain completely neutralizes the beta(S)-chain dependent polymerization.
      The polymerization inhibitory propensity of pig alpha-chain is higher when it is
      present in the cis alpha(P)beta(S) dimer relative to that in a trans
      alpha(P)beta(A) dimer. The semisynthetically generated chimeric pig-human and
      human-pig alpha-chains by exchanging the alpha(1-30) segments of human and pig
      alpha-chains have established that the sequence differences of pig alpha(31-141)
      segment can also completely neutralize the polymerization. Comparison of the
      electrostatic potential energy landscape of the alpha-chain surfaces of HbS and
      alpha(2)(P)beta(2)(S) suggests that the differences in electrostatic potential
      energy surfaces on the alpha-chain of alpha(2)(P)beta(2)(S) relative to that in
      HbS, particularly the ones involving CD region, E-helix and EF-corner of pig
      alpha-chain are responsible for the polymerization neutralization activity. The
      pig and human-pig chimeric alpha-chains can serve as blueprints for the design of
      a new generation of variants of alpha-chain(s) suitable for the gene therapy of
      sickle cell disease.

PMID- 10903877
TI  - Activation of specific MEK-ERK cascade is necessary for TGFbeta signaling and
      crosstalk with PKA and PKC pathways in cultured rat articular chondrocytes.
AB  - OBJECTIVE: TGFbeta is a potent stimulator of cell growth in cultured rat
      articular chondrocytes (CRAC). The stimulatory effect is mediated through the
      immediate induction of c-fos gene by activating ERK of MAPK. The present study
      was undertaken to investigate the upstream regulators involved in TGFbeta-induced
      ERK activation in CRAC and to compare the results with the events in HepG2 cells.
      RESULTS: In vitro kinase and trans-reporting assays showed that TGFbeta
      preferentially activated ERK and JNK pathways in CRAC and HepG2, respectively.
      ERK activation in CRAC was selectively inhibited by PD98059, a MEK inhibitor.
      Overexpression of wild or active forms of MEKK1, the upstream activator of ERK
      and JNK, decreased the TGFbeta-induced 3TP-luciferase activity in CRAC. In
      contrast, in HepG2 dominant negative form of MEKK1 or SEK1 ligand-dependent
      reporter activity was diminished. Transfection of TAK1, another MAPKKK, also
      positively and negatively regulated 3TP transcriptional activity of HepG2 and
      CRAC, respectively. Activation of PKA by 8-bromo-cyclic AMP or forskolin, and
      inhibition of PKC by calphostin C, resulted in a significant decrease in 3TP
      activity as well as in vitro ERK kinase activity in CRAC. CONCLUSIONS: The
      results indicate that TGFbeta transduces a predominant signal pathway through MEK
      ERK-Elk1, independent of MEKK1 or TAK1 pathway in CRAC. However, in HepG2,
      activation of MEKK1 and TAK1 is essential for TGFbeta-induced signal
      transmission. The results also demonstrated that in CRAC, MEK-ERK pathway
      activated by TGFbeta is negatively regulated by PKA cascade but transactivated by
      PKC.

PMID- 10903878
TI  - Osteoarthritis-like lesions in transgenic mice harboring a small deletion
      mutation in type II collagen gene.
AB  - OBJECTIVE: The present study was conducted on transgenic Del1 (+/-) mice
      harboring six copies of a transgene with small deletion mutation engineered into
      mouse type II collagen gene. Incorporation of transgene into mouse genome was
      predicted to cause reduced mechanical strength of articular cartilage with
      deposition of structurally inferior collagen network and consequently to
      predispose the animal to early-onset joint degeneration. DESIGN: Progression of
      degenerative chances in the knee joints of Del1 (+/-) and control mice was
      followed by macroscopic and histologic analyses at 3-5 month intervals between 3
      and 22 months of age. Expression and distribution of type II collagen was studied
      with Northern hybridization, RNase protection assay and immunohistochemistry.
      RESULTS: Articular cartilage degeneration began with superficial fibrillation at
      the age of 3 months in Del1 (+/-) mice. These changes coincided with a
      significant reduction in the expression of both endogenous and transgene-derived
      type II collagen mRNA. The defects gradually progressed into erosions penetrating
      the articular cartilage, bony sclerosis, degeneration of menisci, mineralization
      of various joint structures, cyst formation and exposure of subchondral bone.
      Nontransgenic controls also developed osteoarthritic lesions, but these appeared
      significantly later and were less severe. Increased transcription of type IIA
      procollagen mRNA, typical for chondroprogenitor cells and cartilage repair was
      also observed at six months in Del1 (+/-) mice. CONCLUSION: These findings
      suggest that the impact of truncated type II collagen transgene, together with
      maturation-related reduction in type II collagen production significantly
      contribute to the early-onset degeneration of knee joints in Del1 (+/-) mice.
      These mice with osteoarthritis-like phenotype should provide a useful model for
      studies on the early pathogenic mechanisms involved in articular cartilage
      degeneration.

PMID- 10903879
TI  - Glucosamine HCl reduces equine articular cartilage degradation in explant
      culture.
AB  - Objective To determine whether glucosamine inhibits experimentally induced
      degradation of equine articular cartilage explants. Methods Articular cartilage
      was obtained from the antebrachio-carpal and middle joints of horses (2-8 years
      old) killed for reasons unrelated to lameness. Cartilage discs were harvested
      from the weight-bearing region of the articular surface and cultured. Media were
      exchanged daily and the recovered media stored at 4 degrees C. Explants were
      maintained in basal media 2 days prior to the start of four treatment days. On
      days 1-4 lipopolysaccharide (LPS, 10 microg/ml) or recombinant human interleukin
      1 (rhIL-1, 50 ng/ml) were added to induce cartilage degradation. To test the
      potential protective effects of glucosamine, the compound was added in three
      concentrations (0.25, 2.5, or 25 mg/ml) and treatments were performed in
      triplicate. Controls included wells without LPS, rhIL-1beta, or glucosamine.
      Nitric oxide, proteoglycan and matrix metalloproteinases (MMP) released into
      conditioned media and tissue proteoglycan synthesis were measured as indicators
      of cartilage metabolism. Results Maximal nitric oxide production, proteoglycan
      release, and MMP activity were detected 1 day after the addition of LPS or rhIL
      1beta to the media. The addition of 25 mg/ml of glucosamine prevented the
      increase in nitric oxide production, proteoglycan release and MMP activity
      induced by LPS or rhIL-1. Conclusions These data indicate that glucosamine can
      prevent experimentally induced cartilage degradation in vitro.

PMID- 10903880
TI  - Gene therapy for meniscal injury: enhanced synthesis of proteoglycan and collagen
      by meniscal cells transduced with a TGFbeta(1)gene.
AB  - Objective To determine whether meniscal cells can express a TGFbeta(1)transgene
      delivered by a retroviral vector, and respond to the gene product by increasing
      matrix synthesis. Methods Monolayer cultures of human and canine meniscal cells
      were infected with retroviruses carrying either a human TGFbeta(1)cDNA or marker
      genes. Conditioned media were assayed for the presence of TGFbeta(1).
      Biosynthesis assays using radiolabeled precursors were employed to determine the
      effects of the transgenes on the synthesis of proteoglycan, collagen and
      noncollagenous proteins. Collagen phenotyping was performed by SDS-PAGE. Results
      Media conditioned by canine and human meniscal cells transduced with the
      TGFbeta(1)gene, accumulated several nanograms/10(6)cells of TGFbeta(1)during a 48
      h incubation. Media conditioned by control cells contained very little
      TGFbeta(1). Transduction with the TGFbeta(1)gene, but not marker genes, increased
      the synthesis of collagen and proteoglycan by 8-15-fold. The synthesis of
      noncollagenous proteins was enhanced more modestly. Monolayers of meniscal cells
      synthesized types I, III, V and VI collagen. The TGFbeta(1)gene increased the
      synthesis of all types of collagen without altering the ratios between them.
      Conclusions Meniscal cells are readily transduced by retroviral vectors and
      respond to the transfer of a TGFbeta(1)cDNA by greatly increasing matrix
      synthesis. These findings encourage the further development of genetic approaches
      to the healing of meniscal lesions.

PMID- 10903881
TI  - Altered electrophysiological responses to mechanical stimulation and abnormal
      signalling through alpha5beta1 integrin in chondrocytes from osteoarthritic
      cartilage.
AB  - OBJECTIVE: To establish whether chondrocytes from normal and osteoarthritic human
      articular cartilage recognize and respond to pressure induced mechanical strain
      in a similar manner. DESIGN: Chondrocytes, extracted from macroscopically normal
      and osteoarthritic human articular cartilage obtained from knee joints at
      autopsy, were grown in monolayer culture and subjected to cyclical pressure
      induced strain (PIS) in the absence or presence of anti-integrin antibodies,
      agents known to block ion channels and inhibitors of key molecules involved in
      the integrin-associated signalling pathways. The response of the cells to
      mechanical stimulation was assessed by measuring changes in membrane potential.
      RESULTS: Unlike chondrocytes from normal articular cartilage, which showed a
      membrane hyperpolarization response to PIS, chondrocytes from osteoarthritic
      cartilage responded by membrane depolarization. The mechanotransduction pathway
      involves alpha5beta1 integrins, stretch-activated ion channels, tyrosine kinases
      and phospholipase C but the actin cytoskeleton and protein kinase C, which are
      important in the membrane hyperpolarization response in normal chondrocytes, are
      not necessary for membrane depolarization in osteoarthritic chondrocytes in
      response to PIS. CONCLUSION: Chondrocytes derived from osteoarthritic cartilage
      show a different signalling pathway via alpha5beta1 integrin in response to
      mechanical stimulation which may be of importance in the production of phenotypic
      changes recognized to be present in diseased cartilage.

PMID- 10903882
TI  - Effects of chondroitin sulfate and interleukin-1beta on human chondrocyte
      cultures exposed to pressurization: a biochemical and morphological study.
AB  - Objective This study investigated the in vitro effects of chondroitin sulfate
      (CS) on human articular chondrocytes cultivated in the presence or in the absence
      of interleukin-1beta (IL-1beta) during 10 days of culture with and without
      pressurization cycles. Design The effects of CS (10 and 100 microg/ml) with and
      without IL-1beta were assessed in the culture medium of cells exposed to
      pressurization cycles in the form of synusoidal waves (minimum pressure 1 Mpa,
      maximum pressure 5 Mpa) and a frequency of 0.25 Hz for 3 h by immunoenzymatic
      method on microplates for the quantitative measurement of human proteoglycans
      (PG). On the 4th and 10th day of culture the cells were used for morphological
      analysis by transmission electron microscopy (TEM) and scanning electron
      microscopy (SEM). Results The presence of IL-1beta determines a significant
      decrease in PG concentration measured in the culture medium. When the cells are
      cultured in the presence of IL-1beta and CS, a statistically significant
      restoration of PG levels is observed. Under pressurization conditions, we
      observed that PG concentration in the medium of cells presents a significant
      increase at baseline conditions, in the presence of IL-1beta+CS10 and IL
      1beta+CS100, but not with IL-1beta alone. The results concerning metabolic
      evaluation are confirmed by the morphologic findings obtained by TEM and SEM.
      Conclusions These in vitro studies confirm the protective role of CS, which
      counteracts the IL-1beta induced effects and they confirm the importance of
      pressure on chondrocyte metabolism and morphology.

PMID- 10903883
TI  - Sensitivity of MRI to proteoglycan depletion in cartilage: comparison of sodium
      and proton MRI.
AB  - OBJECTIVE: The purpose of this work was to evaluate the results from sodium and
      proton magnetic resonance imaging (MRI) in detecting small changes in
      proteoglycan (PG) content in bovine articular cartilage specimens. DESIGN:
      Articular cartilage from 15 specimens of bovine patellae were subjected to
      partial PG depletion with different concentrations of trypsin for 30 min. Sodium
      and proton MR images of the intact specimen were obtained on a 4T GE clinical MRI
      system. Two custom-built 7 cm-diameter solenoid coils tuned to proton and sodium
      frequencies were employed. Fast gradient echo and spin echo imaging sequences
      were used to determine sodium density, proton density and proton relaxation times
      (T(1)and T(2)) of the specimens. Spectrophotometric assay was performed after MRI
      to determine PG concentrations of the cartilage specimens. RESULTS: The sodium
      signal change correlated well with the observed PG loss (R(2)=0.85, P< 0.01)
      whereas the proton signal change was inconsistent (R(2)=0.10, P< 0.8). The change
      in proton T(1)and T(2)between the two regions did not correlate with PG loss
      (R(2)=0. 07 and R(2)=0.06, respectively). CONCLUSIONS: Results from these studies
      demonstrate that sodium MRI is both sensitive and specific in detecting small
      changes in PG concentration, whereas proton density and relaxation properties are
      not sensitive to small changes in PG content.

PMID- 10903884
TI  - Activation of annexin II and V expression, terminal differentiation,
      mineralization and apoptosis in human osteoarthritic cartilage.
AB  - OBJECTIVE: To test the hypothesis that terminal differentiation of chondrocytes
      in human osteoarthritic cartilage might lead to the failure of repair mechanisms
      and might cause progressive loss of structure and function of articular
      cartilage. DESIGN: Markers for terminally differentiated chondrocytes, such as
      alkaline phosphatase, annexin II, annexin V and type X collagen, were detected by
      immunohistochemical analysis of human normal and osteoarthritic knee cartilage
      from medial and lateral femoral condyles. Apoptosis in these specimens was
      detected using the TUNEL labeling. Mineralization and matrix vesicles were
      detected by alizarin red S staining and electron microscopic analysis. RESULTS:
      Alkaline phosphatase, annexin II, annexin V and type X collagen were expressed by
      chondrocytes in the upper zone of early stage and late stage human osteoarthritic
      cartilage. However, these proteins, which are typically expressed in hypertrophic
      and calcifying growth plate cartilage, were not detectable in the upper, middle
      and deep zones of healthy human articular cartilage. TUNEL labeling of normal and
      osteoarthritic human cartilage sections provided evidence that chondrocytes in
      the upper zone of late stage osteoarthritic cartilage undergo apoptotic changes.
      In addition, mineral deposits were detected in the upper zone of late stage
      osteoarthritic cartilage. Needle-like mineral crystals were often associated with
      matrix vesicles in these areas, as seen in calcifying growth plate cartilage.
      CONCLUSION: Human osteoarthritic chondrocytes adjacent to the joint space undergo
      terminal differentiation, release alkaline phosphatase-, annexin II- and annexin
      V-containing matrix vesicles, which initiate mineral formation, and eventually
      die by apoptosis. Thus, these cells resume phenotypic changes similar to terminal
      differentiation of chondrocytes in growth plate cartilage culminating in the
      destruction of articular cartilage in osteoarthritis.

PMID- 10903885
TI  - A clinicopathologic study of osteonecrosis in the osteoarthritic hip.
AB  - OBJECTIVE: To investigate the incidence and nature of secondary osteonecrosis
      observed in osteoarthritis (OA) of the femoral head. DESIGN: This study is based
      on a retrospective review of the histopathologic and radiologic materials
      obtained from 906 consecutive cases (1007 femoral heads) diagnosed as OA.
      RESULTS: Secondary osteonecrosis was recognized grossly and confirmed
      microscopically in 38.2% of the femoral heads. The lesions were categorized into
      two types based on shape, size and depth; 'shallow' flat lesion (median axis 3-10
      mm, depth 2-3 mm) with or without cysts (368 cases, 36.5%), and 'deep, wedge
      shaped' large lesion (more than 20 mm across and 10 mm in depth) with or without
      cyst (17 cases, 1.7%). In the 'shallow' flat lesion, the age ranged from 25 to 88
      (average 66), the female/male ratio was 0.8, and the location of osteonecrosis
      correlated best with the direction of migration in OA. In the 'deep, wedge
      shaped' lesion, the age ranged from 56 to 92 (average 70), the female/male ratio
      was 1.8, and the location of osteonecrosis was similar to that found in primary
      osteonecrosis. CONCLUSION: Two different types of osteonecrosis were observed in
      OA. 'Shallow' osteonecrosis may be pressure necrosis as a result of eburnation,
      while 'deep, wedge-shaped' osteonecrosis appears to be an independent phenomena
      presumably caused by similar causal factors to those in primary osteonecrosis.

PMID- 10903886
TI  - Recent advances in human hepatocyte culture systems.

PMID- 10903887
TI  - Suppression of IkappaBalpha expression is necessary for c-Jun N-terminal kinase
      mediated enhancement of Fas cytotoxicity.
AB  - The role of c-Jun N-terminal kinase (JNK) in the regulation of Fas-mediated cell
      death was investigated. Murine L929 fibroblasts were pretreated with anisomycin
      for 1 h to activate JNK, followed by exposure to anti-Fas antibodies/actinomycin
      D (ActD) for 16-24 h. Compared to untreated controls, the induction of JNK
      activation failed to raise cellular sensitivity to anti-Fas/ActD killing.
      Notably, a significant increase in anti-Fas/ActD killing as induced by JNK
      preactivation was observed in L929 cells which were engineered to suppress
      IkappaBalpha protein expression by antisense mRNA. Restoration of the
      IkappaBalpha protein level in these cells by ectopic expression of a cDNA
      construct abolished the JNK-increased anti-Fas/ActD killing. Despite the
      suppression of IkappaBalpha, no constitutive p65 (RelA) NF-kappaB nuclear
      translocation was observed in the IkappaBalpha-antisense cells. Also, inhibition
      of NF-kappaB by curcumin failed to inhibit the JNK-increased Fas cytotoxicity,
      suggesting that NF-kappaB is not involved in the observed effect. Most
      interestingly, culturing of L929 cells on extracellular protein matrices resulted
      in partial suppression of IkappaBalpha expression and constitutive JNK and p42/44
      MAPK activation. Upon stimulation with anisomycin, these matrix protein
      stimulated cells further exhibited reduced IkappaBalpha expression and p42/44
      MAPK activation, as well as became sensitized to JNK-increased anti-Fas/ActD
      killing. Again, ectopic expression of IkappaBalpha in these cells abolished the
      enhanced anti-Fas/ActD killing effect. Together, these results indicate that
      suppression of IkappaBalpha expression is essential for JNK-mediated enhancement
      of Fas cytotoxicity.

PMID- 10903888
TI  - Preferential cleavage sites for Sau3A restriction endonuclease in human ribosomal
      DNA.
AB  - Previous studies of cloned ribosomal DNA (rDNA) variants isolated from the cosmid
      library of human chromosome 13 have revealed some disproportion in
      representativity of different rDNA regions (N. S. Kupriyanova, K. K.
      Netchvolodov, P. M. Kirilenko, B. I. Kapanadze, N. K. Yankovsky, and A. P.
      Ryskov, Mol. Biol. 30, 51-60, 1996). Here we show nonrandom cleavage of human
      rDNA with Sau3A or its isoshizomer MboI under mild hydrolysis conditions. The
      hypersensitive cleavage sites were found to be located in the ribosomal
      intergenic spacer (rIGS), especially in the regions of about 5-5.5 and 11 kb
      upstream of the rRNA transcription start point. This finding is based on
      sequencing mapping of the rDNA insert ends in randomly selected cosmid clones of
      human chromosome 13 and on the data of digestion kinetics of cloned and noncloned
      human genomic rDNA with Sau3A and MboI. The results show that a methylation
      status and superhelicity state of the rIGS have no effect on cleavage site
      sensitivity. It is interesting that all primary cleavage sites are adjacent to or
      entering into Alu or Psi cdc 27 retroposons of the rIGS suggesting a possible
      role of neighboring sequences in nuclease accessibility. The results explain
      nonequal representation of rDNA sequences in the human genomic DNA library used
      for this study.

PMID- 10903889
TI  - Processing of cdk5 activator p35 to its truncated form (p25) by calpain in
      acutely injured neuronal cells.
AB  - Recently, it was shown that conversion of cdk5 activator protein p35 to a C
      terminal fragment p25 promotes a deregulation of cdk5 activity, which may
      contribute to neurodegeneration in Alzheimer's disease. In this study, we present
      evidence that calpain is a protease involved in the conversion of p35 to p25. To
      activate calpain, rat cerebellar granule neurons were treated with maitotoxin
      (MTX). A C-terminus-directed anti-p35 antibody detected that p35 conversion to
      p25 paralleled the formation of calpain-generated alpha-spectrin (alpha-fodrin)
      breakdown products (SBDP's) in a maitotoxin-dose-dependent manner. Two calpain
      inhibitors (MDl28170 and SJA6017) reduced p35 processing but were unchanged when
      exposed to the caspase inhibitor carbobenzoxy-Asp-CH(2)OC(=O)-2, 6
      dichlorobenzene or the proteasome inhibitors (lactacystin and Z-Ile-Glu(OtBu)Ala
      Leu-CHO). p35 protein was also degraded to p25 when rat brain lysate was
      subjected to in vitro digestion with purified mu- and m-calpains. Additionally,
      in a rat temporary middle cerebral artery occlusion model, p35 processing to p25
      again paralleled SBDP formation in the ischemic core. Lastly, in malonate-injured
      rat brains, the ipsilateral side showed a striking correlation of SBDP formation
      with p35 to p25 conversion and tau phosphorylation (at Ser202 and Thr205)
      increase. These data suggest that calpain is a major neuronal protease capable of
      converting p35 to p25 and might play a pathological role of activating cdk5 and
      its phosphorylation of tau in Alzheimer's disease.

PMID- 10903891
TI  - Glutathione transferase M2-2 catalyzes conjugation of dopamine and dopa o
      quinones.
AB  - Human glutathione transferase M2-2 prevents the formation of neurotoxic
      aminochrome and dopachrome by catalyzing the conjugation of dopamine and dopa o
      quinone with glutathione. NMR analysis of dopamine and dopa o-quinone-glutathione
      conjugates revealed that the addition of glutathione was at C-5 to form 5-S
      glutathionyl-dopamine and 5-S-glutathionyl-dopa, respectively. Both conjugates
      were found to be resistant to oxidation by biological oxidizing agents such as
      O(2), H(2)O(2), and O(*-)(2), and the glutathione transferase-catalyzed reaction
      can therefore serve a neuroprotective antioxidant function.

PMID- 10903890
TI  - HASH-1 and E2-2 are expressed in human neuroblastoma cells and form a functional
      complex.
AB  - The basic helix-loop-helix (bHLH) transcription factor mammalian achaete-scute
      homolog-1 (MASH-1 in mouse and HASH-1 in human) is essential for proper
      development of olfactory and most peripheral autonomic neurons, and for the
      formation of distinct neuronal circuits within the central nervous system. We
      have previously shown that HASH-1 is expressed in neuroblastoma tumors and cell
      lines, and in this study we have used the yeast two-hybrid system to isolate HASH
      1 interacting proteins from a human neuroblastoma cDNA library. Two of the
      isolated clones contained cDNA from the E2-2 gene (also known as ITF2/SEF2-1). We
      show that E2-2 interacts with HASH-1 in both yeast and mammalian cells. The HASH
      1/E2-2 complex binds an E-box (CACCTG) in vitro, and transactivates an E-box
      containing reporter construct in vivo. Furthermore, E2-2 seems to be one of the
      major HASH-1 interacting proteins in extracts from neuroblastoma cells. In
      conclusion, E2-2 forms a functional complex with HASH-1, and might therefore be
      involved in the development of specific parts of the central and peripheral
      nervous systems.

PMID- 10903892
TI  - Minimal requirements for the nuclear localization of p27(Kip1), a cyclin
      dependent kinase inhibitor.
AB  - p27(Kip1) is a cyclin-dependent kinase inhibitor, and its nuclear localization is
      a prerequisite for it to function as a cell cycle regulator. In the present
      study, the minimal requirement for the nuclear localization signal (NLS) of
      p27(Kip1) was determined by analyzing the localization of various mutants of
      p27(Kip1) tagged with green fluorescent protein (GFP) in HeLa cells and porcine
      aortic endothelial cells. Wild-type p27(Kip1) exclusively localized into nucleus,
      while GFP alone localized in both cytosol and nucleus. A comparison of various
      truncation mutants revealed residues 153-166 to be the minimal region necessary
      for nuclear localization. However, a fusion of this region to GFP showed
      cytoplasmic retention in addition to nuclear localization, thus suggesting that
      some extension flanking this region is required to achieve a full function of
      NLS. The site-directed mutation of the full-length p27(Kip1) therefore showed
      that four basic residues (K153, R154, K165, R166), especially R166, play a
      critical role in the nuclear localization of p27(Kip1).

PMID- 10903893
TI  - Identification and biochemical localization of a Na-K-Cl cotransporter in the
      human placental cell line BeWo.
AB  - Several transport systems mediating the placental transport of Na, K and Cl have
      been described, but whether the trophoblast membrane also expresses a Na-K-Cl
      cotransporter that mediates the coupled movement of all three ions remains
      unclear. Here we show that BeWo cells, a human trophoblastic cell line, exhibit
      bumetanide-sensitive (86)Rb (a K surrogate) uptake. Entry via this route accounts
      for approximately 17% of the (86)Rb influx with the remainder being mediated
      largely via the Na,K-ATPase. The activity of the bumetanide-sensitive transporter
      was rapidly elevated (>40%) upon subjecting cells to an acute hyperosmotic
      challenge signifying a potential role in cell volume regulation. Antibodies to
      the Na-K-Cl cotransporter identified a single band of approximately 200 kDa on
      Western blots of fractionated BeWo membranes. This immunoreactivity colocalized
      with that of the Na,K-ATPase (a basal membrane marker), but was absent from
      membranes enriched with placental alkaline phosphatase (an apical membrane
      marker). These findings show for the first time, that a Na-K-Cl cotransporter is
      expressed in a human placental cell line which may be involved in regulating
      trophoblast cell volume.

PMID- 10903894
TI  - Genomic structure, chromosomal localization, and expression pattern of the human
      LIM-homeobox3 (LHX 3) gene.
AB  - Lhx3 is a LIM-homeobox protein essential for pituitary development in mice. The
      human homologue gene spans 7.2 kb and contains 7 exons, including two
      alternatively spliced first exons. This structure encodes two distinct protein
      isoforms, LHX3a and LHX3b, that differ exclusively in their amino-terminus. The
      LHX3 gene was localized at 9q34.2-34.3. The predicted protein sequence is highly
      homologous to other known Lhx3 proteins, the highest degree of homology being in
      the conserved domains. The highest expression of LHX3 was found in pituitary
      gland, spinal cord, and lung. Among different pituitary cell types, corticotrophs
      appear to express preferentially LHX3b isoform, suggesting a distinct role of the
      b-form in the development of this cell lineage. Although the human LHX3 gene
      structure would provide a ground for clarification of the molecular basis of
      complete anterior pituitary deficiency, we were unable to identify any mutation
      in the LHX3 gene of 46 such patients.

PMID- 10903895
TI  - Anion protection of CuZnSOD during peroxidative activity with H(2)O(2).
AB  - The "peroxidase" activity of the copper-zinc superoxide dismutase is a poorly
      sustained activity because of the competing inactivation of the enzyme. New
      evidence suggests that the bound oxidant may be partitioning between oxidizing
      the enzyme or oxidizing small anions. At constant peroxide, nitrite and azide
      only partially protect the enzyme (50%) against loss of copper(I) and
      inactivation up to one anion per copper. Beyond that level, there is no further
      protection. Bicarbonate ion also protects, but larger amounts are required. These
      data suggest that there is significant oxidation of the enzyme even in the
      presence of the small anions and therefore the formation of the bound oxidant
      cannot be sustained in a true catalytic process.

PMID- 10903897
TI  - Mechanisms of activation and action of mDial in the formation of parallel stress
      fibers in MDCK cells.
AB  - mDial is a downstream target molecule of Rho small G protein and regulates the
      formation of parallel stress fibers in MDCK cells. mDial consists of at least one
      Rho-binding domain (RBD), one FH3 domain (FH3D), one coiled-coil domain (CCD),
      one FH1 domain (FH1D), one FH2 domain (FH2D), and another CCD in this order from
      the N-terminus to the C-terminus. We constructed various deletion mutants of
      mDial and investigated the mechanisms of its activation and action by measuring
      the formation of parallel stress fibers in MDCK cells. We show here that at least
      FH1D and second CCD are essential for the formation of parallel stress fibers.
      Furthermore, we present the evidence suggesting that mDial has another domain
      which interacts with RBD, that this interaction masks FH1D and second CCD and
      keeps mDial inactive, and that the binding of Rho to RBD opens this folded
      structure, resulting in the activation of mDial.

PMID- 10903896
TI  - Resveratrol inhibits AGEs-induced proliferation and collagen synthesis activity
      in vascular smooth muscle cells from stroke-prone spontaneously hypertensive
      rats.
AB  - Advanced glycation end-products (AGEs) of plasma proteins and/or matrix proteins
      are candidate mediators for various vascular complications such as
      atherosclerosis. We previously reported a significantly larger accumulation of
      AGEs of the aorta in stroke-prone spontaneously hypertensive rats (SHRSP) than in
      age-matched Wistar-Kyoto rats (WKY). In this study, we examined the effects of
      AGEs on vascular smooth muscle cells (VSMC) from SHRSP and WKY rats. We also
      studied the in vitro effects of resveratrol (3, 4',5-trihydroxystilbene), a
      natural phytestrogen, on VSMC proliferation, DNA synthesis, and collagen
      synthesis activity in SHRSP-VSMC. AGEs accelerated the proliferation of SHRSP- or
      WKY-VSMC in a time- and dose-dependent manner. VSMC from SHRSP were more
      sensitive to AGEs than VSMC from normotensive WKY. AGEs also significantly
      increased DNA synthesis and prolyl hydroxylase activity, a marker for collagen
      synthesis, in SHRSP-VSMC. AGEs-induced increases in TGF-beta1 mRNA in SHRSP-VSMC
      were significantly greater than in WKY-VSMC. Resveratrol inhibited AGEs
      stimulated proliferation, DNA synthesis, and prolyl hydroxylase activity in SHRSP
      VSMC in a dose-dependent manner. ICI 182780, a specific estrogen receptor
      antagonist, partly blocked the inhibitory effects of resveratrol on AGEs
      stimulated proliferation, DNA synthesis, and prolyl hydroxylase activity.
      Resveratrol significantly inhibited AGEs-induced TGF-beta1 mRNA increases in a
      dose-dependent manner. Thus, resveratrol may confer protective effects on the
      cardiovascular system by attenuating vascular remodeling and may be clinically
      useful as a safer substitute for feminizing estrogens in preventing
      cardiovascular disease.

PMID- 10903898
TI  - Real-time PCR quantification of full-length and exon 11 spliced BRCA1 transcripts
      in human breast cancer cell lines.
AB  - Germline alterations of the BRCA1 tumor suppressor gene have been implicated at
      least in half of familial breast cancers. Nevertheless, in sporadic breast cancer
      no mutation of this gene has been characterized to date. In sporadic breast
      tumors, other BRCA1 gene loss of function mechanisms, such as down-regulation of
      gene expression, have been suggested. In an effort to better understand the
      relationship between BRCA1 expression and malignant transformation, we have
      adapted the new real-time quantitative PCR method based on a 5' nuclease assay
      and the use of doubly labeled fluorescent TaqMan probes to quantify BRCA1 mRNA.
      We have compared expression of BRCA1 mRNA with or without exon 11 in the normal
      breast epithelial cell line MCF10a and in three cancer cell lines (MCF-7, MDA
      MB231 and HBL100) by comparing two methods of quantification: the comparative
      C(T) and the standard curve. We found that the full length BRCA1 mRNA, which
      encodes the functional nuclear protein, was down-regulated in tumor cells when
      compared with MCF10a cells.

PMID- 10903899
TI  - Cloning of the full-length coding sequence of rat liver-specific organic anion
      transporter-1 (rlst-1) and a splice variant and partial characterization of the
      rat lst-1 gene.
AB  - The full-length coding sequence of rat liver-specific organic anion transporter-1
      (lst-1) and its splice variant have been cloned. The full-length rat lst-1
      (designated rlst-1a) encodes a protein containing 687 amino acids and has 12
      putative transmembrane domains, multiple potential N-glycosylation and
      phosphorylation sites. Therefore, rat lst-1a has 35 additional amino acid
      residues compared to the previously reported rat lst-1. A splice variant
      (designated rlst-1c) reported in this communication encodes a protein containing
      654 amino acids and has 10-putative transmembrane domains. PCR analysis suggests
      that rlst-1a is the most abundant form in liver. Phylogenetic analysis reveals
      that rat lst-1a is an ortholog of human LST-1 (hLST-1) and mouse lst-1 (mlst-1).
      The rlst-1 gene is composed of 15 exons and 14 introns. Analysis of exon-intron
      boundary reveals that the splice variant rlst-1c lacks the entire exon 7, while
      the previously reported rat lst-1 (designated herein as rlst-1b) lacks
      approximately half of exon 10, and the splicing has occurred through alternative
      usage of a splice donor site within exon 10.

PMID- 10903900
TI  - Functional interaction of the immunosuppressant mizoribine with the 14-3-3
      protein.
AB  - Mizoribine (MIZ) is a novel imidazole nucleoside with immunosuppressive activity.
      MIZ has been approved in Japan and combination therapy with MIZ and
      glucocorticoids has been used after renal transplantation and for lupus nephritis
      and rheumatoid arthritis. In this study, we identify 14-3-3 proteins as MIZ
      binding proteins. 14-3-3 proteins interact with many proteins involved in
      cellular signaling, including the glucocorticoid receptor (GR). The 14-3-3/GR
      interaction enhances the transcriptional activity of the receptor. We show that
      MIZ affects the conformation of 14-3-3 proteins and enhances the interaction of
      GR and 14-3-3eta dose dependently in vitro. MIZ also has a stimulatory effect on
      transcriptional activation by the GR. Our results point to the possibility that
      one mechanism for the therapeutic effect of MIZ could be to regulate the GR
      function via 14-3-3 proteins.

PMID- 10903901
TI  - Characterization of the beta-dystroglycan-growth factor receptor 2 (Grb2)
      interaction.
AB  - The beta-dystroglycan/Grb2 interaction was investigated and a proline-rich region
      within beta-dystroglycan that binds Grb2-src homology 3 domains identified. We
      used surface plasmon resonance (SPR), fluorescence analysis, and solid-phase
      binding assay to measure the affinity constants between Grb2 and the beta
      dystroglycan cytoplasmic tail. Analysis of the data obtained from SPR reveals a
      high-affinity interaction (K(D) approximately 240 nM) between Grb2 and the last
      20 amino acids of the beta-dystroglycan carboxyl-terminus, which also contains a
      dystrophin-binding site. A similar K(D) value (K(D) approximately 280 nM) was
      obtained by solid-phase binding assay and in solution by fluorescence. Both Grb2
      SH3 domains bind beta-dystroglycan but the N-terminal SH3 domain binds with an
      affinity approximately fourfold higher than that of the C-terminal SH3 domain.
      The Grb2-beta-dystroglycan interaction was inhibited by dystrophin in a range of
      concentration of 160-400 nM. These data suggest a highly regulated and dynamic
      dystrophin/dystroglycan complex formation and that this complex is involved in
      cell signaling.

PMID- 10903902
TI  - Regiospecific transglycolytic synthesis and structural characterization of 6-O
      alpha-glucopyranosyl-glucopyranose (isomaltose).
AB  - The enzymatic synthesis of 6-O-alpha-glucopyranosyl-glucopyranose (isomaltose)
      was achieved. The regiospecific transglycosylation reaction was catalyzed by a
      crude preparation of alpha-D-glucosidase from Aspergillus niger, using p
      nitrophenyl alpha-D-glucopyranose as the donor and glucopyranose as the acceptor.
      The yield of the reaction was 59% on a molar basis with respect to the donor. The
      structural identity of the product was fully determined by HPLC, HPAEC-PAD,
      ionspray mass spectrometry and (13)C NMR.

PMID- 10903903
TI  - Hsl7p, the yeast homologue of human JBP1, is a protein methyltransferase.
AB  - The yeast protein Hsl7p is a homologue of Janus kinase binding protein 1, JBP1, a
      newly characterized protein methyltransferase. In this report, Hsl7p also is
      shown to be a methyltransferase. It can be crosslinked to [(3)H]S
      adenosylmethionine and exhibits in vitro protein methylation activity. Calf
      histones H2A and H4 and bovine myelin basic protein were methylated by Hsl7p,
      whereas histones H1, H2B, and H3 and bovine cytochrome c were not. We
      demonstrated that JBP1 can complement Saccharomyces cerevisiae with a disrupted
      HSL7 gene as judged by a reduction of the elongated bud phenotype, and a point
      mutation in the JBP1 S-adenosylmethionine consensus binding sequence eliminated
      all complementation by JBP1. Therefore, we conclude the yeast protein Hsl7p is a
      sequence and functional homologue of JBP1. These data provide evidence for an
      intricate link between protein methylation and macroscopic changes in yeast
      morphology.

PMID- 10903904
TI  - Regulation of IL-1beta-mediated MUC2 gene in NCI-H292 human airway epithelial
      cells.
AB  - This study demonstrates for the first time the effects of IL-1beta on the
      regulation of protein production as well as MUC2 gene transcription in cultured
      human airway epithelial cells. The effect of IL-1beta on the regulation of MUC2
      protein was determined by flow cytometric analysis. The expression level of MUC2
      induced by IL-1beta increased in a dose-dependent manner. MUC2 transcripts were
      detected after 2 h of exposure to IL-1beta and reached maximal level after 8 h.
      Actinomycin D experiments indicated that the IL-1beta-mediated MUC2 expression
      was controlled by transcriptional regulation. Both RT-PCR and FACS analysis
      showed that budesonide concomitantly attenuated IL-1beta mediated MUC2 gene as
      well as protein production levels. Use of the glucocorticoid receptor antagonist,
      RU-486, restored the inhibitory effect of budesonide on the IL-1beta-mediated
      MUC2 protein as well as gene. The data suggest that IL-1beta up-regulates MUC2
      gene by transcriptional regulation and that budesonide suppresses the IL-1beta
      medicated MUC2 expression via decreased transcriptional activation.

PMID- 10903905
TI  - Molecular cloning, expression analysis, and chromosome mapping of WDR6, a novel
      human WD-repeat gene.
AB  - The WD-repeat proteins are found in all eukaryotes and play an important role in
      the regulation of a wide variety of cellular functions such as signal
      transduction, transcription, and proliferation. Here we report on the cloning and
      characterization of a novel human WD-repeat gene, WDR6, which encodes a protein
      of 1121 amino acids and contains 11 WD-repeat units. WDR6 is unique since its 11
      WD repeats are clustered into two distinct groups separated by a putative
      transmembrane domain. The WDR6 gene was mapped to chromosome 15q21 by
      fluorescence in situ hybridization. Northern analysis demonstrated that WDR6 is
      ubiquitously expressed in human adult and fetal tissues. WDR6 is not homologous
      to any previously identified human WD-repeat genes including WDR1 through WDR5.
      However, it was found to have significant sequence similarity with Arabidopsis
      thaliana hypothetical protein T7B11.12, yeast putative elongation factor G, and
      probable membrane protein YPL183c. All of them have been defined as WD-repeat
      proteins. Therefore, WDR6 is a novel protein and probably belongs to a highly
      conserved subfamily of WD-repeat proteins in which T7B11.12 and YPL183c are its
      distantly related members.

PMID- 10903906
TI  - Transgenic mice reveal novel sites of calcitonin receptor gene expression during
      development.
AB  - To characterize the tissue and developmental-specific transcriptional activity of
      the human calcitonin receptor (hCTR) gene in vivo, transgenic mice containing a
      4.9-kb hCTR promoter/beta-galactosidase (lacZ) construct were generated. Between
      8.5 and 10.5 days of development, lacZ-positive cells were observed on the
      lateral side of cervical and occipital level somites and in the lateral myotome.
      LacZ-positive cells also appeared to be migrating from the dermomyotome into the
      adjacent limb buds, suggesting that the hCTR promoter is active in hypaxial
      muscle progenitors. By 11.5-16 days of development, novel hCTR expression sites
      were identified that included limb buds, cornea, retina, skin, intercostal
      muscles, muscles of the limbs, face, and dorsal root ganglion. hCTR promoter
      activity in a number of these tissues was repressed at adult stages of
      development. RT-PCR demonstrated endogenous mCTR mRNA in all lacZ-positive
      tissues assayed. The developmental regulation of hCTR gene expression in the
      above tissues suggests that CTRs are likely to play an important role in their
      morphogenesis.

PMID- 10903907
TI  - Temperature-dependent functional expression of a plant K(+) channel in mammalian
      cells.
AB  - The Arabidopsis thaliana potassium channel KAT1 was expressed and characterized
      in Chinese hamster ovary cells. KAT1-GFP fusion protein was successfully targeted
      to the plasma membrane and electrophysiological analysis revealed functional
      expression of KAT1 only in cells cultured at 30 degrees C. The main biophysical
      characteristics of KAT1 are similar to those described for the channel expressed
      in other systems. CHO cells represent an advantageous expression system and may
      be the system of choice to study the expression, assembly, function, and
      regulation of plant potassium channels in general.

PMID- 10903908
TI  - A redox-inactive thioredoxin reduces growth and enhances apoptosis in WEHI7.2
      cells.
AB  - Cancer cell lines transfected with thioredoxin show increased anchorage
      independent growth and decreased sensitivity to induction of apoptosis by a
      number of anticancer drugs. The present studies were undertaken to evaluate
      further the role of thioredoxin in cell growth and drug-induced apoptosis. A
      redox-inactive mutant thioredoxin was stably transfected into WEHI7.2 mouse
      lymphocytic leukemia cells and two clones were examined for growth
      characteristics and the induction of apoptosis by dexamethasone, etoposide,
      doxorubicin, and staurosporine. These clones each exhibited a 71% increase in
      doubling time in solution and a 20 and 75% reduction in colony formation in soft
      agarose. The transfected cells also showed increased susceptibility to apoptosis
      induced by dexamethasone, etoposide, doxorubicin, and staurosporine compared with
      controls. The results of this study suggest that thioredoxin can regulate the
      growth rate of cells and that thioredoxin is a critical component in the pathway
      leading to drug-induced apoptosis in WEHI7.2 cells.

PMID- 10903909
TI  - Contortrostatin activates ERK2 and tyrosine phosphorylation events via distinct
      pathways.
AB  - We report that cells adhering to contortrostatin show transient increases in
      activation of Extracellular signal Regulated Kinase 2 (ERK2). The kinetics and
      degree of activation are similar to cells adhering to fibronectin or vitronectin.
      We have recently shown that contortrostatin induces tyrosine phosphorylation in
      tumor cells. Contortrostatin is shown here to stimulate activation of ERK2 in
      suspended cells, but this activation follows a different dose-response pattern
      than contortrostatin-induced tyrosine phosphorylation. Since contortrostatin
      induces tyrosine phosphorylation via alphavbeta3, we explored the effects of an
      alphavbeta3-blocking antibody, 7E3, on contortrostatin-stimulated ERK2
      activation. While 7E3 completely blocks the effect of contortrostatin on tyrosine
      phosphorylation, this antibody had no effect on activation of ERK2. In cells
      lacking expression of alphavbeta3, tyrosine phosphorylation was unaffected by
      contortrostatin treatment, but ERK2 was activated. This is strong evidence that
      contortrostatin is regulating tyrosine phosphorylation events and ERK2 activation
      via separate pathways and through different integrin receptors.

PMID- 10903910
TI  - Genomic organization and amplification of the human epidermal type II keratin
      genes K1 and K5.
AB  - Keratins are a family of structurally related proteins that form the intermediate
      filament cytoskeleton in epithelial cells. Mutations in K1 and K5 result in the
      autosomal dominant disorders epidermolytic hyperkeratosis/bullous congenital
      ichthyosiform erythroderma and epidermolysis bullosa simplex, respectively. Most
      disease-associated mutations are within exons encoding protein domains involved
      in keratin filament assembly. However, some mutations occur outside the mutation
      hot-spots and may perturb intermolecular interactions between keratins and other
      proteins, usually with milder clinical consequences. To screen the entire keratin
      1 and keratin 5 genes we have characterized their intron-exon organization. The
      keratin 1 gene comprises 9 exons spanning approximately 5.6 kb on 12q, and the
      keratin 5 gene comprises 9 exons spanning approximately 6.1 kb on 12q. We have
      also developed a comprehensive PCR-based mutation detection strategy using
      primers placed on flanking introns followed by direct sequencing of the PCR
      products.

PMID- 10903911
TI  - Solubilization of the chemokine receptor CXCR4.
AB  - The chemokine receptor CXCR4 was solubilized from the human T-cell line CEM by
      using the detergent n-dodecyl-beta-maltoside (DDM) and cholesteryl hemisuccinate
      ester (CHS). Binding studies with (125)I-SDF-1alpha revealed a dissociation
      constant of 5.33 nM and a receptor density (B(max)) of 2.68 pmol/mg in CEM
      membranes at 4 degrees C. The affinity of solubilized CXCR4 for SDF-1alpha was
      identical to membrane-bound CXCR4. Binding of gp120 to solubilized CXCR4 was
      demonstrated by coprecipitation of gp120 with anti-CXCR4 antibodies.

PMID- 10903912
TI  - A novel rice (Oryza sativa L.) acidic PR1 gene highly responsive to cut,
      phytohormones, and protein phosphatase inhibitors.
AB  - A novel rice acidic pathogenesis-related (PR) class 1 cDNA (OsPR1a) was isolated
      from jasmonic acid (JA)-treated rice seedling leaf. The OsPR1a cDNA is 830 bp
      long and contains an open reading frame of 507 nucleotides encoding 168 amino
      acid residues with a predicted molecular mass of 17,560 and pI of 4.4. The
      deduced amino acid sequence of OsPR1a has a high level of identity with acidic
      and basic PR1 proteins from plants. Southern analysis revealed that OsPR1a is a
      member of a multigene family. The OsPR1a gene was found to be cut-inducible,
      whereas the phytohormones JA, salicylic acid (SA), 3-indoleacetic acid,
      gibberellin, and ethylene (using ethylene generator ethephon, ET) enhanced
      accumulation of OsPR1a transcript, as well as the protein phosphatase inhibitors
      cantharidin (CN) and endothall (EN). Induced expression of OsPR1a gene by JA, CN
      or EN, and ET was light/dark- and dose-dependent and was almost completely
      inhibited by cycloheximide. Dark downregulated CN-, EN-, and ET-induced OsPR1a
      gene expression, whereas it was further enhanced with JA. SA and abscisic acid
      blocked JA-induced OsPR1a transcript. Simultaneous application of staurosporine
      (ST) enhances CH- or EN-induced OsPR1a transcript, but not with JA. This is the
      first report on cloning of a rice acidic PR1 gene (OsPR1a), which is regulated by
      phytohormones, phosphorylation/dephosphorylation event(s), and light.

PMID- 10903913
TI  - Induction of tryptophan 2,3-dioxygenase in the mouse endometrium during
      implantation.
AB  - Indoleamine 2,3-dioxygenase (IDO) is expressed in trophoblasts and defends the
      conceptus against rejection by reducing the tryptophan level and suppressing the
      T cell activity. We isolated a cDNA for tryptophan 2,3-dioxygenase (TDO), another
      key catabolizing enzyme of tryptophan, from a mouse uterus cDNA library enriched
      with pregnancy-induced genes. Northern blot and in situ hybridization analyses
      demonstrated that the TDO mRNA was induced in the decidualized stromal cells
      around the implanted embryo at the time of implantation. The expression was then
      upregulated and primarily localized at the mesometrial decidua. TDO mRNA was
      induced by deciduoma formation as well as embryo transfer but not by ovarian
      steroid hormones. These findings demonstrated that TDO is induced in the
      endometrial stromal cells concomitant with decidualization and suggested its
      involvement in the implantation process by regulating the tryptophan level at the
      implantation site.

PMID- 10903914
TI  - Identification and expression of a novel 3'-exon of mouse
      Runx1/Pebp2alphaB/Cbfa2/AML1 gene.
AB  - Cbfa1 (recently renamed as Runx2) is prerequisite for the differentiation of
      osteoblasts that play a central role in regulation of bone metabolism. Runx
      transcription factors belong to Drosophila pair rule gene "runt" family that also
      play critical roles during the development of hematopoietic tissues or insect
      bodies. To identify novel sequences related to Runx (Cbfa) genes, we screened a
      11 d.p.c (days postcoitum) mouse embryonic cDNA library using a probe
      corresponding to Runx2 (Cbfa1) runt domain and identified a novel cDNA fragment.
      This cDNA (521-41) is about 2.4 kb in length and contains a sequence identical to
      the N-terminal half of mouse Runx1 (Pebp2alphaB/Cbfa2/AML1b) and a novel protein
      coding sequence in the C-terminal region. High expression levels of 521-41 mRNA
      were observed during the early mouse embryogenesis. In adult mice, 521-41 mRNA
      was expressed ubiquitously in lumbar vertebrae, brain, kidney, heart, muscle, and
      ovary. We also found that 521-41 mRNA was constitutively expressed in an
      osteoblast-like cell line, MC3T3E1. These data indicate that 521-41 gene is a
      novel splicing variant of mouse Runx1 which is expressed in skeletal tissues and
      osteoblast-like cells.

PMID- 10903915
TI  - Nucleoredoxin, glutaredoxin, and thioredoxin differentially regulate NF-kappaB,
      AP-1, and CREB activation in HEK293 cells.
AB  - Well-established mechanisms for regulation of protein activity include thiol
      mediated oxidoreduction in addition to protein-protein interactions and
      phosphorylation. Nucleoredoxin (NRX), glutaredoxin (GRX), and thioredoxin (TRX)
      have been shown to act as a potent thiol reductase and reactive oxygen species
      regulator. They constitute a oxidoreductase superfamily and have been suggested
      as a candidate operating in the redox regulation of gene expression. We
      demonstrated here that intracellular localization of these redox molecules differ
      from each other and that the redox molecules differentially regulate NF-kappaB,
      AP-1, and CREB activation induced by TNFalpha, PMA, and forskolin and by
      expression of signaling intermediate kinases, NIK, MEKK, and PKA in HEK293 cells.
      This is a first report that describes involvement of NRX and GRX and differences
      from TRX in transcriptional regulation of NF-kappaB, AP-1, and CREB in living
      cells.

PMID- 10903916
TI  - Nitric oxide and cytochrome c oxidase: mechanisms of inhibition and NO
      degradation.
AB  - NO inhibits mitochondrial respiration by reacting with either the reduced or the
      oxidized binuclear site of cytochrome c oxidase, leading respectively to
      accumulation of cytochrome a(2+)(3)-NO or cytochrome a(3+)(3)-NO(-)(2) species.
      Exploiting the unique light sensitivity of the cytochrome a(2+)(3)-NO, we show
      that under turnover conditions, depending on the cytochrome c(2+) concentration,
      either the cytochrome a(2+)(3)-NO or the nitrite-bound enzyme is formed. The
      predominance of one of the two inhibitory pathways depends on the occupancy of
      the turnover intermediates. In the dark, the respiration recovers at the rate of
      NO dissociation (k' = 0.01 s(-1) at 37 degrees C). Illumination of the sample
      speeds up recovery rate only at higher reductant concentrations, indicating that
      the inhibited species is cytochrome a(2+)(3)-NO. When the reaction occurs with
      the oxidized binuclear site, light has no effect and NO is oxidized to harmless
      nitrite eventually released in the bulk, accounting for catalytic NO degradation.

PMID- 10903917
TI  - Restriction landmark genomic scanning of mouse liver tumors for gene
      amplification: overexpression of cyclin A2.
AB  - SV40 T/t antigen-induced liver tumors from transgenic mice were analyzed by
      Restriction Landmark Genomic Scanning (RLGS). Using NotI as the restriction
      landmark, RLGS targets CpG islands found in gene-rich regions of the genome.
      Since many RLGS landmarks are mapped, the candidate gene approach can be used to
      help determine which genes are altered in tumors. RLGS analysis revealed one
      tumor-specific amplification mapping close to CcnA2 (cyclin A2) and Fgf2
      (fibroblast growth factor 2). Southern analysis confirmed that both oncogenes are
      amplified in this tumor and in a second, independent liver tumor. Whereas Fgf2
      RNA is undetectable in tumors, CcnA2 RNA and cyclin A2 protein was overexpressed
      in 25 and 50% of tumors, respectively. Combining RLGS with the candidate gene
      approach indicates that cyclin A2 amplification and overexpression is a likely
      selected event in transgenic mouse liver tumors. Our results also indicate that
      our mouse model for liver tumorigenesis in mice accurately recapitulates events
      observed in human hepatocellular carcinoma.

PMID- 10903918
TI  - Salicylate metabolites inhibit cyclooxygenase-2-dependent prostaglandin E(2)
      synthesis in murine macrophages.
AB  - The poor cyclooxygenase (COX) inhibitor and major aspirin metabolite salicylic
      acid is known to exert analgesic and anti-inflammatory effects by still
      unidentified mechanisms. In RAW 264.7 macrophages, lipopolysaccharide (LPS)
      induced COX-2-dependent synthesis of prostaglandin E(2) (PGE(2)) was suppressed
      by aspirin (IC(50) of 5. 35 microM), whereas no significant inhibition was
      observed in the presence of sodium salicylate and the salicylate metabolite
      salicyluric acid at concentrations up to 100 microM. However, the salicylate
      metabolite gentisic acid (2,5-dihydroxybenzoic acid; 10-100 microM) and salicyl
      coenzyme A (100 microM), the intermediate product in the formation of salicyluric
      acid from salicylic acid, significantly suppressed LPS-induced PGE(2) production.
      In contrast, gamma-resorcylic acid (2,6-dihydroxybenzoic acid) as well as
      unconjugated coenzyme A failed to affect prostanoid synthesis, implying that the
      para-substitution of hydroxy groups and the activated coenzyme A thioester are
      important for COX-2 inhibition. Using real-time RT-PCR, none of the salicylate
      derivatives tested were found to interfere with COX-2 expression. Overall, our
      results suggest that certain metabolites of salicylic acid may contribute to the
      pharmacological action of its parent compound by inhibiting COX-2-dependent
      PGE(2) formation at sites of inflammation.

PMID- 10903919
TI  - HBV polymerase interacts independently with N-terminal and C-terminal fragments
      of Hsp90beta.
AB  - Hsp90 is an abundant chaperone protein that assists the folding of specific
      proteins, such as steroid receptors, protein kinases, and so on, for their proper
      function. TP and RT domains of HBV polymerase have been also shown to be
      associated with Hsp90. Therefore, the identification of the binding sites within
      Hsp90, responsible for forming Hsp90/HBV Pol complex, is important for the
      understanding of HBV replication. In this study, cotransfection and
      immunoprecipitation experiments were performed to localize the binding sites of
      HBV pol to Hsp90. Our data show that HBV pol interact independently with both N
      terminal and C-terminal fragments of Hsp90. Further analysis showed that N
      terminal fragment (1-302) of Hsp90 interacts with both TP and RT domains of HBV
      pol, whereas C-terminal fragment (438-723) interacts with only RT domain. In
      conclusion, we showed that HBV pol independently interacts with N-terminal and C
      terminal fragments, but not the middle fragment (327-438) of Hsp90.

PMID- 10903920
TI  - Immediate and neurotoxic effects of HIV protein gp120 act through CXCR4 receptor.
AB  - Primary rat hippocampal neurones show pronounced elevations of intracellular
      calcium within minutes of exposure to the HIV coat protein gp120. Culture of
      hippocampal neurones with gp120 causes significant neurotoxicity. We find that
      the peptide VSLSYRCPCRFF, a competitive inhibitor of the CXCR4 chemokine
      receptor, markedly inhibits toxicity and eliminates the acute calcium elevation.
      CXCR4 receptors are thought to signal to the Gi/Go family of trimeric GTP binding
      proteins. Pretreatment of hippocampal neurones with pertussis toxin to inactivate
      Gi/Go proteins markedly reduced gp120 neurotoxicity. These results indicate that
      both short and long term effects of gp120 are the result of activation of the
      CXCR4 receptor.

PMID- 10903921
TI  - Functional expression and biophysical properties of polymorphic variants of the
      human gap junction protein connexin37.
AB  - Connexin37 (Cx37) forms gap junction channels between endothelial cells, and two
      polymorphic Cx37 variants (Cx37-S319 and Cx37-P319) have been identified with a
      possible link to atherosclerosis. We studied the gap junction channel properties
      of these hCx37 polymorphs by expression in stably transfected communication
      deficient cells (N2A and RIN). We also expressed a third, truncated variant (Cx37
      fs254Delta293) and Cx37 constructs containing epitope tags added to their amino
      or carboxyl termini. All Cx37 constructs were produced by the transfected cells
      as demonstrated by RT-PCR and immunoblotting and trafficked to appositional
      surfaces between cells as demonstrated by immunofluorescence microscopy. Dual
      whole cell patch-clamping studies demonstrated that Cx37-P319, Cx37-S319, and
      Cx37-fs254Delta293 had large unitary conductances ( approximately 300 pS).
      However, addition of an amino terminal T7 tag (T7-Cx37-fs254Delta293) produced a
      single channel conductance of 120-145 pS with a 24-30 pS residual state.
      Moreover, the kinetics of the voltage-dependent decline in junctional current for
      T7-Cx37-fs254Delta293 were significantly slower than for the wild type, implying
      a destabilization of the transition state. These data suggest that the amino
      terminus of Cx37 plays a significant role in gating as well as conductance. The
      carboxyl terminal tail has lesser influence on unitary conductance and
      inactivation kinetics.

PMID- 10903922
TI  - Lack of obvious 50 kilobase pair DNA fragments in DNA fragmentation factor 45
      deficient thymocytes upon activation of apoptosis.
AB  - The DNA fragmentation factor 45 (DFF45/ICAD) is a key subunit of a heterodimeric
      DNase complex critical for the induction of DNA fragmentation during apoptosis in
      vivo. To further assess the importance of DFF45 in chromosomal DNA degradation,
      we induced apoptosis in wild-type control and DFF45 deficient thymocytes and
      compared the cleavage of chromosomal DNA to 50 kilobase pair size fragments. We
      found that there is a lack of obvious large chromosomal DNA fragments upon
      treatments by various apoptotic agents in DFF45 deficient thymocytes. The major
      organ systems in the DFF45 mutant mice either two months or fifteen months of age
      appear normal. These results suggest that functional DFF45 is required for
      cleavage of DNA into both large size and oligonucleosomal size fragments in
      thymocytes during apoptosis. However, deficiency in DFF45 apparently does not
      significantly affect normal mouse development and tissue homeostasis.

PMID- 10903923
TI  - CFTR-Mediated anion conductance regulates Na(+)-K(+)-pump activity in Calu-3
      human airway cells.
AB  - We studied the role of CFTR in the Na(+)-K(+)-pump activity of Calu-3 human
      airway cells. To estimate the Na(+)-K(+)-pump activity on the basolateral
      membrane, the ouabain-sensitive component of the short-circuit current (Isc) was
      measured after permeabilization of the apical membrane with nystatin, a Na(+)
      ionophore. The Na(+)-K(+)-pump activity was diminished by a selective CFTR
      blocker (glybenclamide) or nonspecific Cl(-) channel inhibitors (NPPB and DPC)
      but not by outwardly rectifying Cl(-) channel blockers (DNDS, DIDS). Augmentation
      of anion conductance by 8-bromo-cyclic AMP (8Br-cAMP, 1 mM) potentiated the Na(+)
      K(+)-pump activity that was reduced by blocking CFTR or by the replacement of Cl(
      ) with gluconate, a less membrane-permeant anion. The Na(+)-K(+)-pump activity
      was unaffected by the replacement of Cl(-) with NO(-)(3) that has equal
      permeability through the CFTR. These results suggest that the anion movement
      through the CFTR may contribute to the Na(+)-K(+)-pump activity in Calu-3 cells
      by regulating the rate of Na(+) entry.

PMID- 10903924
TI  - The effect of monovalent ions on polyphosphate binding to Escherichia coli
      exopolyphosphatase.
AB  - The thermodynamic driving force for the interaction of Escherichia coli
      exopolyphosphatase (PPX) with polyphosphate was investigated by varying salt
      choice and concentration. This interaction was found to be cation concentration
      independent but weakly dependent on the concentration of certain anions. Both of
      these traits are very uncommon for nonspecific protein-polyelectrolyte
      interactions. Interpretation of these results based on theory indicated that
      binding was not entropy driven due to release of polyelectrolyte-condensed
      counterions, as is the case for nearly all protein-polyelectrolyte interactions.
      The thermodynamics of the PPX-polyphosphate interaction showed similarity only to
      the interaction of polynucleotides with single stranded binding proteins.

PMID- 10903925
TI  - Endothelial cell proliferation induced by HARP: implication of N or C terminal
      peptides.
AB  - HARP (Heparin Affin Regulatory Peptide) is a 18-kDa secreted protein displaying
      high affinity for heparin. It has neurite outgrowth-promoting activity, while
      there are conflicting results regarding its mitogenic activity. In the present
      work, we studied the effect of human recombinant HARP expressed in bacterial
      cells as well as two peptides (HARP residues 1-21 and residues 121-139) on the
      proliferation of three endothelial cell types derived from human umbilical vein
      (HUVEC), rat adrenal medulla (RAME), and bovine brain capillaries (BBC) either
      added as a soluble form in the cell culture medium or coated onto the culture
      plate. HARP added in a soluble form in the culture medium had no effect on the
      proliferation of BBC, HUVEC, and RAME cells. However, when immobilized onto the
      cell culture plate, HARP had a concentration-dependent mitogenic effect on both
      BBC cells and HUVEC. The peptides presented as soluble factor induced a
      significant concentration-dependent mitogenic effect on BBC cells but only a
      small effect on HUVEC and RAME cells. When they were immobilized onto the cell
      culture plate, the mitogenic effect was much greater. The most responsive cells
      were BBC that expressed and secreted in the culture medium the higher amounts of
      HARP.

PMID- 10903926
TI  - Osteoblast maturation suppressed osteoclastogenesis in coculture with bone marrow
      cells.
AB  - The analysis of co-culture system using osteoblast and bone marrow indicated that
      the mineralized osteoblast decreased osteoclast formation. This finding was an
      incentive to better investigate the relation of osteoblast development and
      osteoclastogenesis. The expression of osteoclast differentiation factor
      (ODF/RANKL) mRNA and protein dramatically decreased. Alternatively, macropharge
      colony stimulation factor (M-CSF/CSF-1) transcription and protein secreted in
      media slightly decreased as the development of osteoblast. On the other hands,
      mRNA expression and the secretion to the culture medium of osteoclastogenesis
      inhibitory factor (OPG/OCIF) didn't significantly change depending on osteoblast
      differentiation. We conclude that osteoblast development might suppress
      osteoclastogenesis especially with the decrease of ODF/RANKL.

PMID- 10903927
TI  - A common pathway for nitric oxide release from NO-aspirin and glyceryl
      trinitrate.
AB  - NO-Aspirin (NCX-4016) releases nitric oxide (NO) in biological systems through as
      yet unidentified mechanisms. In LLC-PK1 kidney epithelial cells, a 5-h
      pretreatment with glyceryl trinitrate (GTN, 0.1-1 microM) significantly
      attenuated the cyclic GMP response to a subsequent challenge with both NO-aspirin
      or GTN. Similarly, NO-aspirin (10-100 microM) was found to induce tolerance to
      its own cyclic GMP stimulatory action and to that of GTN. In contrast, cyclic GMP
      stimulation by the spontaneous NO donor SIN-1, which releases NO independently of
      enzymatic catalysis, remained unimpaired in cells pretreated with GTN or NO
      aspirin. The observed cross-tolerance between NO-aspirin and GTN cells indicates
      that bioactivation pathways of organic nitrates, which have been shown to involve
      cytochrome P450, may also be responsible for NO release from NO-aspirin.
      Prolonged treatment with NO-aspirin causes down-regulation of the cellular cyclic
      GMP response, suggesting that tolerance may occur during therapy with NO-aspirin.

PMID- 10903928
TI  - A small structural element, Pc-J5/5a, plays dual roles in a group IC1 intron RNA.
AB  - The P4-P6 domain of group IC1 intron ribozymes such as that of the Tetrahymena
      autonomously folds into a hairpin-shaped structure in which the J5/5a region
      serves as a hinge. Phylogenetic comparisons of these IC1 introns suggested that
      the J5/5a region (termed Pc-J5/5a motif) in a subclass of IC1 introns such as the
      one from Pneumocystis carinii functions not only as a hinge but also as a
      receptor for a GAAA-tetraloop. We investigated the role of this motif by
      transplanting the structural unit, Pc-J5/5a motif, of Pneumocystis carinii into
      the P4-P6 domain of the Tetrahymena intron. The results showed that the Pc-J5/5a
      motif binds to a GAAA loop with high affinity and also facilitates the bending of
      the Tetrahymena P4-P6 domain more positively than the original J5/5a region.

PMID- 10903929
TI  - A member of a gene family on Xp22.3, VCX-A, is deleted in patients with X-linked
      nonspecific mental retardation.
AB  - X-linked nonspecific mental retardation (MRX) has a frequency of 0.15% in the
      male population and is caused by defects in several different genes on the human
      X chromosome. Genotype-phenotype correlations in male patients with a partial
      nullisomy of the X chromosome have suggested that at least one locus involved in
      MRX is on Xp22.3. Previous deletion mapping has shown that this gene resides
      between markers DXS1060 and DXS1139, a region encompassing approximately 1.5 Mb
      of DNA. Analyzing the DNA of 15 males with Xp deletions, we were able to narrow
      this MRX critical interval to approximately 15 kb of DNA. Only one gene, VCX-A
      (variably charged, X chromosome mRNA on CRI-S232A), was shown to reside in this
      interval. Because of a variable number of tandem 30-bp repeats in the VCX-A gene,
      the size of the predicted protein is 186-226 amino acids. VCX-A belongs to a gene
      family containing at least four nearly identical paralogues on Xp22.3 (VCX-A, -B,
      -B1, and -C) and two on Yq11.2 (VCY-D, VCY-E), suggesting that the X and Y copies
      were created by duplication events. We have found that VCX-A is retained in all
      patients with normal intelligence and is deleted in all patients with mental
      retardation. There is no correlation between the presence or absence of VCX-B1, 
      B, and VCX-C and mental status in our patients. These results suggest that VCX-A
      is sufficient to maintain normal mental development.

PMID- 10903930
TI  - Tightly clustered 11q23 and 22q11 breakpoints permit PCR-based detection of the
      recurrent constitutional t(11;22).
AB  - Palindromic AT-rich repeats (PATRRs) on chromosomes 11q23 and 22q11 at the
      constitutional t(11;22) breakpoint are predicted to induce genomic instability,
      which mediates the translocation. A PCR-based translocation-detection system for
      the t(11;22) has been developed with PCR primers flanking the PATRRs of both
      chromosomes, to examine the involvement of the PATRRs in the recurrent
      rearrangement. Forty unrelated carriers of the t(11;22) balanced translocation,
      plus two additional, independent cases with the supernumerary-der(22) syndrome,
      were analyzed to compare their translocation breakpoints. Similar translocation
      specific junction fragments were obtained from both derivative chromosomes in all
      40 carriers of the t(11;22) balanced translocation and from the der(22) in both
      of the offspring with unbalanced supernumerary-der(22) syndrome, suggesting that
      the breakpoints in all cases localize within these PATRRs and that the
      translocation is generated by a similar mechanism. This PCR strategy provides a
      convenient technique for rapid diagnosis of the translocation, indicating its
      utility for prenatal and preimplantation diagnosis in families including carriers
      of the balanced translocation.

PMID- 10903931
TI  - Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the
      bone morphogenetic protein receptor-II gene.
AB  - Familial primary pulmonary hypertension is a rare autosomal dominant disorder
      that has reduced penetrance and that has been mapped to a 3-cM region on
      chromosome 2q33 (locus PPH1). The phenotype is characterized by monoclonal
      plexiform lesions of proliferating endothelial cells in pulmonary arterioles.
      These lesions lead to elevated pulmonary-artery pressures, right-ventricular
      failure, and death. Although primary pulmonary hypertension is rare, cases
      secondary to known etiologies are more common and include those associated with
      the appetite-suppressant drugs, including phentermine-fenfluramine. We genotyped
      35 multiplex families with the disorder, using 27 microsatellite markers; we
      constructed disease haplotypes; and we looked for evidence of haplotype sharing
      across families, using the program TRANSMIT. Suggestive evidence of sharing was
      observed with markers GGAA19e07 and D2S307, and three nearby candidate genes were
      examined by denaturing high-performance liquid chromatography on individuals from
      19 families. One of these genes (BMPR2), which encodes bone morphogenetic protein
      receptor type II, was found to contain five mutations that predict premature
      termination of the protein product and two missense mutations. These mutations
      were not observed in 196 control chromosomes. These findings indicate that the
      bone morphogenetic protein-signaling pathway is defective in patients with
      primary pulmonary hypertension and may implicate the pathway in the nonfamilial
      forms of the disease.

PMID- 10903932
TI  - Structural basis for chitin recognition by defense proteins: GlcNAc residues are
      bound in a multivalent fashion by extended binding sites in hevein domains.
AB  - BACKGROUND: Many plants respond to pathogenic attack by producing defense
      proteins that are capable of reversible binding to chitin, a polysaccharide
      present in the cell wall of fungi and the exoskeleton of insects. Most of these
      chitin-binding proteins include a common structural motif of 30 to 43 residues
      organized around a conserved four-disulfide core, known as the 'hevein domain' or
      'chitin-binding' motif. Although a number of structural and thermodynamic studies
      on hevein-type domains have been reported, these studies do not clarify how
      chitin recognition is achieved. RESULTS: The specific interaction of hevein with
      several (GlcNAc)(n) oligomers has been studied using nuclear magnetic resonance
      (NMR), analytical ultracentrifugation and isothermal titration microcalorimetry
      (ITC). The data demonstrate that hevein binds (GlcNAc)(2-4) in 1:1 stoichiometry
      with millimolar affinity. In contrast, for (GlcNAc)(5), a significant increase in
      binding affinity is observed. Analytical ultracentrifugation studies on the
      hevein-(GlcNAc)(5,8) interaction allowed detection of protein-carbohydrate
      complexes with a ratio of 2:1 in solution. NMR structural studies on the hevein
      (GlcNAc)(5) complex showed the existence of an extended binding site with at
      least five GlcNAc units directly involved in protein-sugar contacts. CONCLUSIONS:
      The first detailed structural model for the hevein-chitin complex is presented on
      the basis of the analysis of NMR data. The resulting model, in combination with
      ITC and analytical ultracentrifugation data, conclusively shows that recognition
      of chitin by hevein domains is a dynamic process, which is not exclusively
      restricted to the binding of the nonreducing end of the polymer as previously
      thought. This allows chitin to bind with high affinity to a variable number of
      protein molecules, depending on the polysaccharide chain length. The biological
      process is multivalent.

PMID- 10903933
TI  - D-Ala-D-X ligases: evaluation of D-alanyl phosphate intermediate by MIX, PIX and
      rapid quench studies.
AB  - BACKGROUND: The D-alanyl-D-lactate (D-Ala-D-Lac) ligase is required for synthesis
      of altered peptidoglycan (PG) termini in the VanA phenotype of vancomycin
      resistant enterococci (VRE), and the D-alanyl-D-serine (D-Ala-D-Ser) ligase is
      required for the VanC phenotype of VRE. Here we have compared these with the
      Escherichia coli D-Ala-D-Ala ligase DdlB for formation of the enzyme-bound D
      alanyl phosphate, D-Ala(1)-PO(3)(2-) (D-Ala(1)-P), intermediate. RESULTS: The
      VanC2 ligase catalyzes a molecular isotope exchange (MIX) partial reaction,
      incorporating radioactivity from (14)C-D-Ser into D-Ala-(14)C-D-Ser at a rate of
      0.7 min(-1), which approaches kinetic competence for the reversible D-Ala(1)-P
      formation from the back direction. A positional isotope exchange (PIX) study with
      the VanC2 and VanA ligases displayed a D-Ala(1)-dependent bridge to nonbridge
      exchange of the oxygen-18 label of [gamma-(18)O(4)]-ATP at rates of up to 0.6
      min(-1); this exchange was completely suppressed by the addition of the second
      substrate D-Ser or D-Lac, respectively, as the D-Ala(1)-P intermediate was swept
      in the forward direction. As a third criterion for formation of bound D-Ala(1)-P,
      we conducted rapid quench studies to detect bursts of ADP formation in the first
      turnover of DdlB and VanA. With E. coli DdlB, there was a burst amplitude of ADP
      corresponding to 26-30% of the DdlB active sites, followed by the expected steady
      state rate of 620-650 min(-1). For D-Ala-D-Lac and D-Ala-D-Ala synthesis by VanA,
      we measured a burst of 25-30% or 51% of active enzyme, respectively. CONCLUSIONS:
      These three approaches support the rapid (more than 1000 min(-1)), reversible
      formation of the enzyme intermediate D-Ala(1)-P by members of the D-Ala-D-X
      (where X is Ala, Ser or Lac) ligase superfamily.

PMID- 10903934
TI  - Improving SH3 domain ligand selectivity using a non-natural scaffold.
AB  - BACKGROUND: Src homology 3 (SH3) domains bind sequences bearing the consensus
      motif PxxP (where P is proline and x is any amino acid), wherein domain
      specificity is mediated largely by sequences flanking the PxxP core. This
      specificity is limited, however, as most SH3 domains show high ligand cross
      reactivity. We have recently shown that diverse N-substituted residues (peptoids)
      can replace the prolines in the PxxP motif, yielding a new source of ligand
      specificity. RESULTS: We have tested the effects of combining multiple peptoid
      substitutions with specific flanking sequences on ligand affinity and
      specificity. We show that by varying these different elements, a ligand can be
      selectively tuned to target a single SH3 domain in a test set. In addition, we
      show that by making multiple peptoid substitutions, high-affinity ligands can be
      generated that completely lack the canonical PxxP motif. The resulting ligands
      can potently disrupt natural SH3-mediated interactions. CONCLUSIONS: Peptide
      peptoid hybrid scaffolds yield SH3 ligands with markedly improved domain
      selectivity, overcoming one of the principal challenges in designing inhibitors
      against these domains. These compounds represent important leads in the search
      for orthogonal inhibitors of SH3 domains, and can serve as tools for the
      dissection of complex signaling pathways.

PMID- 10903935
TI  - Robust charge transport in DNA double crossover assemblies.
AB  - BACKGROUND: Multiple-stranded DNA assemblies, encoded by sequence, have been
      constructed in an effort to self-assemble nanodevices of defined molecular
      architecture. Double-helical DNA has been probed also as a molecular medium for
      charge transport. Conductivity studies suggest that DNA displays semiconductor
      properties, whereas biochemical studies have shown that oxidative damage to B-DNA
      at the 5'-G of a 5'-GG-3' doublet can occur by charge transport through DNA up to
      20 nm from a photo-excited metallointercalator. The possible application of DNA
      assemblies, in particular double crossover (DX) molecules, in electrical
      nanodevices prompted the design of a DNA DX assembly with oxidatively sensitive
      guanine moieties and a tethered rhodium photo-oxidant strategically placed to
      probe charge transport. RESULTS: DX assemblies support long-range charge
      transport selectively down the base stack bearing the intercalated photo-oxidant.
      Despite tight packing, no electron transfer (ET) crossover to the adjacent base
      stack is observed. Moreover, the base stack of a DX assembly is well-coupled and
      less susceptible than duplex DNA to stacking perturbations. Introducing a double
      mismatch along the path for charge transport entirely disrupts long-range ET in
      duplex DNA, but only marginally decreases it in the analogous stack within DX
      molecules. CONCLUSIONS: The path for charge transport in a DX DNA assembly is
      determined directly by base stacking. As a result, the two closely packed stacks
      within this assembly are electronically insulated from one another. Therefore, DX
      DNA assemblies may serve as robust, insulated conduits for charge transport in
      nanoscale devices.

PMID- 10903936
TI  - Phorboid 20-homovanillates induce apoptosis through a VR1-independent mechanism.
AB  - BACKGROUND: Vanilloids, such as capsaicin and resiniferatoxin (RTX), are
      recognized at the cell surface by vanilloid receptor type 1 (VR1), which has
      recently been cloned. VR1 mediates the effects of capsaicin and RTX in VR1
      expressing cells, but vanilloids can induce apoptosis through a pathway not
      mediated by VR1. Phorboid 20-homovanillates can be used to investigate cell death
      induced by vanilloids. RESULTS: 12,13-Diacylphorbol-20 homovanillates were
      prepared by the sequential esterification of the natural polyol. Phorbol 12
      phenylacetate 13-acetate 20-homovanillate (PPAHV) induced apoptosis in Jurkat
      cells to the same extent as RTX. Apoptosis was preceded by an increase in
      intracellular reactive oxygen species and by the loss of mitochondrial
      transmembrane potential. PPAHV-induced apoptosis was mediated by a pathway
      involving caspase-3 activation and was initiated at the S phase of the cell
      cycle. The cell-death pathway triggered by VR1 activation was studied in 293T
      cells transfected with the cloned rat vanilloid receptor. In this system,
      capsaicin and PPAHV induced cell death by an apparent necrotic mechanism, which
      was selectively inhibited by the competitive vanilloid receptor antagonist
      capsazepine. Interestingly, phorbol-12, 13-bisnonanoate-20-homovanillate, an
      analogue of PPAHV, induced cell death in VR1-transfected cells but could not
      trigger apoptosis in the Jurkat cell line. CONCLUSIONS: Vanilloids can induce
      cell death through different signalling pathways. The cell death induced in a VR1
      independent manner has the hallmark of apoptosis, whereas the cell death mediated
      by vanilloids binding to VR1 is seemingly necrotic. Phorboid homovanillates that
      have antitumour and anti-inflammatory activities but lack the undesirable side
      effects of the natural vanilloids could be developed as potential drugs.

PMID- 10903937
TI  - A novel artificial loop scaffold for the noncovalent constraint of peptides.
AB  - BACKGROUND: Few examples exist of peptides of < 35 residues that form a stable
      tertiary structure without disulfide bonds. A method for stabilization and
      noncovalent constraint of relatively short peptides may allow the construction
      and use of intracellular peptide libraries containing protein minidomains.
      RESULTS: We have examined a novel method for the noncovalent constraint of
      peptides by attaching the peptide EFLIVKS (single-letter amino acid code), which
      forms dimers, to the amino and carboxyl termini of different peptide inserts. An
      18 residue random coil taken from the inhibitor loop of barley chymotrypsin
      inhibitor 2 was inserted between the peptides to produce a 32-mer minidomain that
      is attacked only slowly by elastase, has numerous slowly exchanging protons,
      contains a high beta-structure content and has a T(m) above 37 degrees C. A point
      mutation disrupting the hydrophobic interior in both dimerizing peptides causes a
      loss of all slowly exchanging protons and of secondary structure. Adding specific
      charged residues to each terminus substantially increased the T(m), as did point
      mutants designed to add interdimerizer ion pairs. Three flexible epitope tag
      inserts and a nonamer insert do not appear to be folded in a stable structure by
      EFLIVKS. The properties of two peptides selected for expression in HeLa cells
      suggest they do form a stable tertiary structure. CONCLUSIONS: Attaching short
      dimerizing peptides to both the amino and carboxyl termini of several 18-mer
      peptides appears to create stable monomeric tertiary structures. Mutations in the
      dimerizers can either destabilize or significantly stabilize a standard 18-mer
      insert. Dimerizing peptides flanking random insert sequences could be used as a
      strategy to generate heterogeneous peptide libraries with both extended and
      folded members.

PMID- 10903938
TI  - Structure-based drug design: the discovery of novel nonpeptide orally active
      inhibitors of human renin.
AB  - BACKGROUND: The aspartic proteinase renin plays an important physiological role
      in the regulation of blood pressure. It catalyses the first step in the
      conversion of angiotensinogen to the hormone angiotensin II. In the past, potent
      peptide inhibitors of renin have been developed, but none of these compounds has
      made it to the end of clinical trials. Our primary aim was to develop novel
      nonpeptide inhibitors. Based on the available structural information concerning
      renin-substrate interactions, we synthesized inhibitors in which the peptide
      portion was replaced by lipophilic moieties that interact with the large
      hydrophobic S1/S3-binding pocket in renin. RESULTS: Crystal structure analysis of
      renin-inhibitor complexes combined with computational methods were employed in
      the medicinal-chemistry optimisation process. Structure analysis revealed that
      the newly designed inhibitors bind as predicted to the S1/S3 pocket. In addition,
      however, these compounds interact with a hitherto unrecognised large, distinct,
      sub-pocket of the enzyme that extends from the S3-binding site towards the
      hydrophobic core of the enzyme. Binding to this S3(sp) sub-pocket was essential
      for high binding affinity. This unprecedented binding mode guided the drug-design
      process in which the mostly hydrophobic interactions within subsite S3(sp) were
      optimised. CONCLUSIONS: Our design approach led to compounds with high in vitro
      affinity and specificity for renin, favourable bioavailability and excellent oral
      efficacy in lowering blood pressure in primates. These renin inhibitors are
      therefore potential therapeutic agents for the treatment of hypertension and
      related cardiovascular diseases.

PMID- 10903940
TI  - Towards the nonstick egg: designing fluorous proteins.
AB  - Anyone who has made scrambled eggs will have had cause to praise the properties
      of Teflon. Teflon's highly chemically inert and nonstick nature derives from the
      perfluorinated polymer polytetrafluoroethylene. Perfluorocarbons have unique and
      valuable physical properties not found in nature. By incorporating fluorine into
      proteins, it might be possible to produce biological molecules with novel and
      useful properties.

PMID- 10903939
TI  - Chemical modification of epibatidine causes a switch from agonist to antagonist
      and modifies its selectivity for neuronal nicotinic acetylcholine receptors.
AB  - BACKGROUND: Studies of ligand gated channels strongly rely on the availability of
      compounds that can activate or inhibit with high selectivity one set or a subset
      of defined receptors. The alkaloid epibatidine (EPB), originally isolated from
      the skin of an Ecuadorian poison frog, is a very specific agonist for the
      neuronal nicotinic acetylcholine receptors (nAChRs). We used EPB derivatives to
      investigate the pharmacophore of nAChR subtypes. RESULTS: Optically pure
      enantiomers of EPB analogues were synthesised. Analogues were obtained altered in
      the aromatic part: the chlorine was eliminated and the relative position of the
      pyridyl nitrogen changed. Voltage clamp electrophysiology was performed with
      these compounds on neuronal nAChRs reconstituted in Xenopus oocytes. The EPB
      derivatives show different activities towards the various nAChR subtypes.
      CONCLUSIONS: Small changes in the molecular structure of EPB produce marked
      changes in its capacity to activate the nAChRs. Subtype specificity can be
      obtained by changing the position of or by eliminating the pyridyl nitrogen.

PMID- 10903941
TI  - Novel cofactors via post-translational modifications of enzyme active sites.
AB  - Recent crystallographic and biochemical studies have revealed the existence of
      numerous novel post-translational modifications within enzyme active sites. These
      modifications create structural and functional diversity. Although the function
      and biosynthesis of some of these modifications are well understood, others need
      further investigation.

PMID- 10903942
TI  - Targeting delivery of paclitaxel into tumor cells via somatostatin receptor
      endocytosis.
AB  - BACKGROUND: The binding of somatostatin (SST) to endogenous G-protein-coupled
      receptors (SST receptors or SSTRs) is followed by internalization of SST, and,
      several reports have shown that a high density of SSTRs is present on most
      hormone-secreting tissue tumors. Facile synthesis of the long-acting SST analog,
      octreotide, has previously been described. Octreotide might be of practical value
      in developing tumor tracers and in serving as a carrier of cytotoxic antitumor
      drugs. RESULTS: Fluorescein-labeled octreotide was internalized into the cytosol
      of human breast MCF-7 carcinoma cells via binding to SSTRs. Octreotide-conjugated
      paclitaxel (taxol) was created by coupling taxol-succinate to the amino-terminal
      end of octreotide. This conjugate retains the biological activity of taxol in
      inducing formation of tubulin bundles, eventually causing apoptosis of MCF-7
      cells. Cytotoxicity of octreotide-conjugated taxol is mainly mediated by SSTR, as
      shown by the observation that octreotide pretreatment can rescue the induced cell
      death. In comparison with free taxol, this conjugate shows much less toxicity in
      Chinese hamster ovary cells. CONCLUSIONS: Octreotide-conjugated taxol exerts the
      same antitumor effect of free taxol on stabilizing microtubule formation and
      inducing cell death. This conjugate triggers tumor cell apoptosis mediated by
      SSTRs and is exclusively toxic to SSTR-expressing cells. Octreotide-conjugated
      taxol is less toxic to low-SSTR-expressing cells compared with free taxol. Our
      results strongly indicated that octreotide-conjugated taxol demonstrates cell
      selectivity and may be used as a targeting agent for cancer therapy.

PMID- 10903943
TI  - A water channel in the core of the vitamin B(12) RNA aptamer.
AB  - BACKGROUND: The 3.0 A crystal structure of the vitamin B(12) RNA aptamer revealed
      an unusual tertiary structure that is rich in novel RNA structural motifs.
      Important details of the interactions that stabilize noncanonical base pairing
      and the role of solvent in the structure were not apparent owing to the limited
      resolution. RESULTS: The structure of the vitamin B(12) RNA aptamer in complex
      with its ligand has been determined at 2.3 A resolution by X-ray crystallography.
      The crystallographic asymmetric unit contains five independent copies of the
      aptamer-vitamin B(12) complex, making it possible to accurately define well
      conserved features. The core of the aptamer contains an unusual water-filled
      channel that is buried between the three strands of an RNA triplex. Well-ordered
      water molecules positioned within this channel form bridging hydrogen bonds and
      stabilize planar base triples that otherwise lack significant direct base-base
      contacts. The water channel terminates at the interface between the RNA and the
      bound ligand, leaving a pair of water molecules appropriately positioned to
      hydrogen bond with the highly polarized cyanide nitrogen of vitamin B(12).
      Analysis of the general solvation patterns for each nucleotide suggests that
      water molecules are not precisely positioned, as observed in previous RNA duplex
      structures, but instead might adjust in response to the varying local
      environment. Unusual intermolecular base pairing contributes to the formation of
      three different dimerization contacts that drive formation of the crystal
      lattice. CONCLUSIONS: The structure demonstrates the important role of water
      molecules and noncanonical base pairing in driving the formation of RNA tertiary
      structure and facilitating specific interactions of RNAs with other molecules.

PMID- 10903944
TI  - How a protein generates a catalytic radical from coenzyme B(12): X-ray structure
      of a diol-dehydratase-adeninylpentylcobalamin complex.
AB  - BACKGROUND: Adenosylcobalamin (coenzyme B(12)) serves as a cofactor for enzymatic
      radical reactions. The adenosyl radical, a catalytic radical in these reactions,
      is formed by homolysis of the cobalt-carbon bond of the coenzyme, although the
      mechanism of cleavage of its organometallic bond remains unsolved. RESULTS: We
      determined the three-dimensional structures of diol dehydratase complexed with
      adeninylpentylcobalamin and with cyanocobalamin at 1.7 A and 1.9 A resolution,
      respectively, at cryogenic temperatures. In the adeninylpentylcobalamin complex,
      the adenine ring is bound parallel to the corrin ring as in the free form and
      methylmalonyl-CoA-mutase-bound coenzyme, but with the other side facing pyrrole
      ring C. All of its nitrogen atoms except for N(9) are hydrogen-bonded to
      mainchain amide oxygen and amide nitrogen atoms, a sidechain hydroxyl group, and
      a water molecule. As compared with the cyanocobalamin complex, the sidechain of
      Seralpha224 rotates by 120 degrees to hydrogen bond with N(3) of the adenine
      ring. CONCLUSIONS: The structure of the adenine-ring-binding site provides a
      molecular basis for the strict specificity of diol dehydratase for the coenzyme
      adenosyl group. The superimposition of the structure of the free coenzyme on that
      of enzyme-bound adeninylpentylcobalamin demonstrated that the tight enzyme
      coenzyme interactions at both the cobalamin moiety and adenine ring of the
      adenosyl group would inevitably lead to cleavage of the cobalt-carbon bond.
      Rotation of the ribose moiety around the glycosidic linkage makes the 5'-carbon
      radical accessible to the hydrogen atom of the substrate to be abstracted.

PMID- 10903945
TI  - Combining structure-based design with phage display to create new Cys(2)His(2)
      zinc finger dimers.
AB  - BACKGROUND: Several strategies have been reported for the design and selection of
      novel DNA-binding proteins. Most of these studies have used Cys(2)His(2) zinc
      finger proteins as a framework, and have focused on constructs that bind DNA in a
      manner similar to Zif268, with neighboring fingers connected by a canonical
      (Kruppel-type) linker. This linker does not seem ideal for larger constructs
      because only modest improvements in affinity are observed when more than three
      fingers are connected in this manner. Two strategies have been described that
      allow the productive assembly of more than three canonically linked fingers on a
      DNA site: connecting sets of fingers using linkers (covalent), or assembling sets
      of fingers using dimerization domains (non-covalent). RESULTS: Using a
      combination of structure-based design and phage display, we have developed a new
      dimerization system for Cys(2)His(2) zinc fingers that allows the assembly of
      more than three fingers on a desired target site. Zinc finger constructs
      employing this new dimerization system have high affinity and good specificity
      for their target sites both in vitro and in vivo. Constructs that recognize an
      asymmetric binding site as heterodimers can be obtained through substitutions in
      the zinc finger and dimerization regions. CONCLUSIONS: Our modular zinc finger
      dimerization system allows more than three Cys(2)His(2) zinc fingers to be
      productively assembled on a DNA-binding site. Dimerization may offer certain
      advantages over covalent linkage for the recognition of large DNA sequences. Our
      results also illustrate the power of combining structure-based design with phage
      display in a strategy that assimilates the best features of each method.

PMID- 10903946
TI  - Crystal structure of N-carbamyl-D-amino acid amidohydrolase with a novel
      catalytic framework common to amidohydrolases.
AB  - BACKGROUND: N-carbamyl-D-amino acid amidohydrolase (DCase) catalyzes the
      hydrolysis of N-carbamyl-D-amino acids to the corresponding D-amino acids, which
      are useful intermediates in the preparation of beta-lactam antibiotics. To
      understand the catalytic mechanism of N-carbamyl-D-amino acid hydrolysis, the
      substrate specificity and thermostability of the enzyme, we have determined the
      structure of DCase from Agrobacterium sp. strain KNK712. RESULTS: The crystal
      structure of DCase has been determined to 1.7 A resolution. The enzyme forms a
      homotetramer and each monomer consists of a variant of the alpha + beta fold. The
      topology of the enzyme comprises a sandwich of parallel beta sheets surrounded by
      two layers of alpha helices, this topology has not been observed in other
      amidohydrolases such as the N-terminal nucleophile (Ntn) hydrolases. CONCLUSIONS:
      The catalytic center could be identified and consists of Glu46, Lys126 and
      Cys171. Cys171 was found to be the catalytic nucleophile, and its nucleophilic
      character appeared to be increased through general-base activation by Glu46.
      DCase shows only weak sequence similarity with a family of amidohydrolases,
      including beta-alanine synthase, aliphatic amidases and nitrilases, but might
      share highly conserved residues in a novel framework, which could provide a
      possible explanation for the catalytic mechanism for this family of enzymes.

PMID- 10903947
TI  - Towards a structural understanding of Friedreich's ataxia: the solution structure
      of frataxin.
AB  - BACKGROUND: Lesions in the gene for frataxin, a nuclear-encoded mitochondrial
      protein, cause the recessively inherited condition Friedreich's ataxia. It is
      thought that the condition arises from disregulation of mitochondrial iron
      homeostasis, with concomitant oxidative damage leading to neuronal death. Very
      little is, as yet, known about the biochemical function of frataxin. RESULTS:
      Here, we show that the mature form of recombinant frataxin behaves in solution as
      a monodisperse species that is composed of a 15-residue-long unstructured N
      terminus and an evolutionarily conserved C-terminal region that is able to fold
      independently. The structure of the C-terminal domain consists of a stable seven
      stranded antiparallel beta sheet packing against a pair of parallel helices. The
      structure is compact with neither grooves nor cavities, features that are typical
      of iron-binding modules. Exposed evolutionarily conserved residues cover a broad
      area and all cluster on the beta-sheet face of the structure, suggesting that
      this is a functionally important surface. The effect of two clinically occurring
      mutations on the fold was checked experimentally. When the mature protein was
      titrated with iron, no tendency to iron-binding or to aggregation was observed.
      CONCLUSIONS: Knowledge of the frataxin structure provides important guidelines as
      to the nature of the frataxin binding partner. The absence of all the features
      expected for an iron-binding activity, the large conserved area on its surface
      and lack of evidence for iron-binding activity strongly support an indirect
      involvement of frataxin in iron metabolism. The effects of point mutations
      associated with Friedreich's ataxia can be rationalised by knowledge of the
      structure and suggest possible models for the occurrence of the disease in
      compound heterozygous patients.

PMID- 10903948
TI  - The X-ray crystal structure of neuronal Sec1 from squid sheds new light on the
      role of this protein in exocytosis.
AB  - BACKGROUND: Sec1-like molecules have been implicated in a variety of eukaryotic
      vesicle transport processes including neurotransmitter release by exocytosis.
      They regulate vesicle transport by binding to a t-SNARE from the syntaxin family.
      This process is thought to prevent SNARE complex formation, a protein complex
      required for membrane fusion. Whereas Sec1 molecules are essential for
      neurotransmitter release and other secretory events, their interaction with
      syntaxin molecules seems to represent a negative regulatory step in secretion.
      RESULTS: Here we report the X-ray crystal structure of a neuronal Sec1 homologue
      from squid, s-Sec1, at 2.4 A resolution. Neuronal s-Sec1 is a modular protein
      that folds into a V-shaped three-domain assembly. Peptide and mutagenesis studies
      are discussed with respect to the mechanism of Sec1 regulation. Comparison of the
      structure of squid s-Sec1 with the previously determined structure of rat
      neuronal Sec1 (n-Sec1) bound to syntaxin-1a indicates conformational
      rearrangements in domain III induced by syntaxin binding. CONCLUSIONS: The
      crystal structure of s-Sec1 provides the molecular scaffold for a number of
      molecular interactions that have been reported to affect Sec1 function. The
      structural differences observed between s-Sec1 and the structure of a rat n-Sec1
      syntaxin-1a complex suggest that local conformational changes are sufficient to
      release syntaxin-1a from neuronal Sec1, an active process that is thought to
      involve additional effector molecule(s).

PMID- 10903949
TI  - Insights into molybdenum cofactor deficiency provided by the crystal structure of
      the molybdenum cofactor biosynthesis protein MoaC.
AB  - BACKGROUND: The molybdenum cofactor (Moco) is an essential component of a large
      family of enzymes involved in important transformations in carbon, nitrogen and
      sulfur metabolism. The Moco biosynthetic pathway is evolutionarily conserved and
      found in archaea, eubacteria and eukaryotes. In humans, genetic deficiencies of
      enzymes involved in this pathway trigger an autosomal recessive and usually
      deadly disease with severe neurological symptoms. The MoaC protein, together with
      the MoaA protein, is involved in the first step of Moco biosynthesis. RESULTS:
      MoaC from Escherichia coli has been expressed and purified to homogeneity and its
      crystal structure determined at 2 A resolution. The enzyme is organized into a
      tightly packed hexamer with 32 symmetry. The monomer consists of an antiparallel,
      four-stranded beta sheet packed against two long alpha helices, and its fold
      belongs to the ferredoxin-like family. Analysis of structural and biochemical
      data strongly suggests that the active site is located at the interface of two
      monomers in a pocket that contains several strictly conserved residues.
      CONCLUSIONS: Asp128 in the putative active site appears to be important for
      catalysis as its replacement with alanine almost completely abolishes protein
      activity. The structure of the Asp128-->Ala variant reveals substantial
      conformational changes in an adjacent loop. In the human MoaC ortholog,
      substitution of Thr182 with proline causes Moco deficiency, and the corresponding
      substitution in MoaC severely compromises activity. This residue is located near
      the N-terminal end of helix alpha4 at an interface between two monomers. The MoaC
      structure provides a framework for the analysis of additional dysfunctional
      mutations in the corresponding human gene.

PMID- 10903950
TI  - X-ray structure of Escherichia coli pyridoxine 5'-phosphate oxidase complexed
      with FMN at 1.8 A resolution.
AB  - BACKGROUND: Escherichia coli pyridoxine 5'-phosphate oxidase (PNPOx) catalyzes
      the terminal step in the biosynthesis of pyridoxal 5'-phosphate (PLP), a cofactor
      used by many enzymes involved in amino acid metabolism. The enzyme oxidizes
      either the 4'-hydroxyl group of pyridoxine 5'-phosphate (PNP) or the 4'-primary
      amine of pyridoxamine 5'-phosphate (PMP) to an aldehyde. PNPOx is a homodimeric
      enzyme with one flavin mononucleotide (FMN) molecule non-covalently bound to each
      subunit. A high degree of sequence homology among the 15 known members of the
      PNPOx family suggests that all members of this group have similar three
      dimensional folds. RESULTS: The crystal structure of PNPOx from E. coli has been
      determined to 1.8 A resolution. The monomeric subunit folds into an eight
      stranded beta sheet surrounded by five alpha-helical structures. Two monomers
      related by a twofold axis interact extensively along one-half of each monomer to
      form the dimer. There are two clefts at the dimer interface that are symmetry
      related and extend from the top to the bottom of the dimer. An FMN cofactor that
      makes interactions with both subunits is located in each of these two clefts.
      CONCLUSIONS: The structure is quite similar to the recently deposited 2.7 A
      structure of Saccharomyces cerevisiae PNPOx and also, remarkably, shares a common
      structural fold with the FMN-binding protein from Desulfovibrio vulgaris and a
      domain of chymotrypsin. This high-resolution E. coli PNPOx structure permits
      predictions to be made about residues involved in substrate binding and
      catalysis. These predictions provide testable hypotheses, which can be answered
      by making site-directed mutants.

PMID- 10903951
TI  - Localization and characterization of the hyaluronan-binding site on the link
      module from human TSG-6.
AB  - BACKGROUND: The interactions of hyaluronan (HA) with proteins are important in
      extracellular matrix integrity and leukocyte migration and are usually mediated
      by a domain termed a Link module. Although the tertiary structure of a Link
      module has been determined, the molecular basis of HA-protein interactions
      remains poorly understood. RESULTS: Isothermal titration calorimetry was used to
      characterize the interaction of the Link module from human TSG-6 (Link_TSG6) with
      HA oligosaccharides of defined length (HA(4)-HA(16)). All oligomers bound (except
      HA(4)) with K(d) values ranging from 0.2-0.5 microM at 25 degrees C. The reaction
      is exothermic with a favourable entropy and the thermodynamic profile is similar
      to those of other glycosaminoglycan-protein interactions. The HA(8) recognition
      site on Link_TSG6 was localized by comparing nuclear magnetic resonance (NMR)
      spectra from a 1:1 complex with free protein. Residues perturbed on HA binding
      include both amino acids that are likely to be directly involved in the
      interaction (i.e., Lys11, Tyr59, Asn67, Phe70, Lys72 and Tyr78) and those
      affected by a ligand-induced conformational change in the beta4/beta5 loop. The
      sidechain of Asn67 becomes more rigid in the complex suggesting that it is in
      close proximity to the binding site. CONCLUSIONS: In TSG-6 a single Link module
      is sufficient for a high-affinity interaction with HA. The HA-binding surface on
      Link_TSG6 is found in a similar position to that suggested previously for CD44,
      indicating that its location might be conserved across the Link module
      superfamily. Here we find no evidence for the involvement of linear sequence
      motifs in HA binding.

PMID- 10903952
TI  - Luxury accommodations: the expanding role of structural plasticity in protein
      protein interactions.
AB  - The recognition of multiple ligands at a single molecular surface is essential to
      many biological processes. Conformational flexibility has emerged as a compelling
      strategy for association at such convergent binding sites. Studies over the past
      few years have brought about a greater understanding of the role that protein
      plasticity might play in protein-protein interactions.

PMID- 10903953
TI  - Crystal structure of the apoptotic suppressor CrmA in its cleaved form.
AB  - BACKGROUND: Cowpox virus expresses the serpin CrmA (cytokine response modifier A)
      in order to avoid inflammatory and apoptotic responses of infected host cells.
      The targets of CrmA are members of the caspase family of proteases that either
      initiate the extrinsic pathway of apoptosis (caspases 8 and 10) or trigger
      activation of the pro-inflammatory cytokines interleukin-1beta and interleukin-18
      (caspase 1). RESULTS: We have determined the structure of a cleaved form of CrmA
      to 2.26 A resolution. CrmA has the typical fold of a cleaved serpin, even though
      it lacks the N-terminal half of the A helix, the entire D helix, and a portion of
      the E helix that are present in all other known serpins. The reactive-site loop
      of CrmA was mutated to contain the optimal substrate recognition sequence for
      caspase 3; however, the mutation only marginally increased the ability of CrmA to
      inhibit caspase 3. Superposition of the reactive-site loop of alpha1-proteinase
      inhibitor on the cleaved CrmA structure provides a model for virgin CrmA that can
      be docked to caspase 1, but not to caspase 3. CONCLUSIONS: CrmA exemplifies viral
      economy, selective pressure having resulted in a 'minimal' serpin that lacks the
      regions not needed for structural integrity or inhibitory activity. The docking
      model provides an explanation for the selectivity of CrmA. Our demonstration that
      engineering optimal substrate recognition sequences into the CrmA reactive-site
      loop fails to generate a good caspase 3 inhibitor is consistent with the docking
      model.

PMID- 10903954
TI  - Screening for phasing atoms in protein crystallography.

PMID- 10903956
TI  - D(2) dopamine receptors enable delta(9)-tetrahydrocannabinol induced memory
      impairment and reduction of hippocampal extracellular acetylcholine
      concentration.
AB  - 1. The systemic administration of Delta(9)-tetrahydrocannabinol (2.5 - 7.5 mg kg(
      1)) reduced hippocampal extracellular acetylcholine concentration and impaired
      working memory in rats. 2. Both effects were antagonized not only by the CB(1)
      cannabinoid receptor antagonist SR141716A (0.5 mg kg(-1), i.p.) but also
      unexpectedly by the D(2) dopamine receptor antagonist S(-)-sulpiride (5, 10 and
      25 mg kg(-1), i.p.). Conversely, Delta(9)-tetrahydrocannabinol-induced memory
      impairment and inhibition of hippocampal extracellular acetylcholine
      concentration were potentiated by the subcutaneous administration of the D(2)
      dopamine receptor agonist (-)-quinpirole (25 and 500 microg kg(-1)). The
      inhibition of hippocampal extracellular acetylcholine concentration and working
      memory produced by the combination of (-)-quinpirole and Delta(9)
      tetrahydrocannabinol was suppressed by either SR141716A or S(-)-sulpiride. 3. Our
      findings suggest that impairment of working memory and inhibition of hippocampal
      extracellular acetylcholine concentration are mediated by the concomitant
      activation of D(2) dopamine and CB(1) cannabinoid receptors, and that D(2)
      dopamine receptor antagonists may be useful in the treatment of the cognitive
      deficits induced by marijuana.

PMID- 10903955
TI  - Mechanisms of nitric oxide-independent relaxations induced by carbachol and
      acetylcholine in rat isolated renal arteries.
AB  - 1. In rat isolated renal artery segments contracted with 0.1 microM phenylephrine
      and in the presence of the NO synthase inhibitor N(omega)-nitro-L-arginine methyl
      ester (L-NAME), carbachol and acetylcholine produced endothelium-dependent
      relaxations. The mechanisms underlying these relaxations were studied. 2. These
      relaxations were not affected by ODQ (1H-[1,2,4]oxadiazolo[4,3, -a]quinoxalin-1
      one) or indomethacin. In arteries contracted with 20 - 30 mM K(+), L-NAME
      resistant relaxations induced by carbachol and acetylcholine were virtually
      absent. 3. The Na(+)-K(+) ATPase inhibitor ouabain reduced these relaxations in a
      concentration-dependent manner. 4. In K(+)-free media, addition of K(+) (5 mM)
      produced 90. 5+/-3.9% (n=3) relaxation of phenylephrine-induced tone. This
      relaxation was endothelium-independent and ouabain-sensitive. 5.
      Tetraethylammonium (TEA), charybdotoxin (ChTX) and iberiotoxin (IbTX) reduced the
      sensitivity of carbachol-induced relaxations, but did not change the maximal
      response. These relaxations were not altered by 4-aminopyridine (4-AP),
      glibenclamide or apamin. Acetylcholine (1 microM)-induced relaxation was reduced
      by ChTX, but not by TEA or IbTX. 6. The cytochrome P450 inhibitor miconazole, but
      not 17-octadecynoic acid, reduced the sensitivity of carbachol-induced
      relaxations, without changing the maximal response. 7. In conclusion, in rat
      isolated renal arteries, acetylcholine and carbachol produced a non-NO/non-PGI(2)
      relaxation which is mediated by an endothelium-derived hyperpolarizing factor
      (EDHF). This factor does not appear to be a cytochrome P450 metabolite. The
      inhibition by ouabain of these relaxations suggests the possible involvement of
      Na(+)-K(+) ATPase activation in EDHF responses, although other mechanisms cannot
      be totally ruled out.

PMID- 10903957
TI  - Inhibition of mouse neuromuscular transmission and contractile function by
      okadaic acid and cantharidin.
AB  - 1. Phosphorylations of cellular proteins modulate biological activities. The
      effects of okadaic acid (0.1 - 10 microM) and cantharidin (1 - 100 microM),
      inhibitors of protein phosphatases, on the synaptic transmission at the mouse
      neuromuscular junction were explored. 2. Both inhibitors almost completely
      depressed twitch forces elicited by electrical stimulation of diaphragm muscles
      (the IC(50)s for okadaic acid and cantharidin were 1.1+/-0.2 and 13+/-1 microM,
      n=5, respectively) and suppressed contractures evoked by high K(+) and ryanodine
      more than 70%. Contractures caused by cardiotoxin, which destroys the integrity
      of sarcolemma, were not depressed. 3. Both okadaic acid (10 microM) and
      cantharidin (100 microM) depolarized muscle membranes from approximately -80 to
      approximately -60 mV in a partially reversible and tetrodotoxin-sensitive manner.
      The initial short-term enhancement of twitch responses (up to approximately 40%)
      was correlated with the inhibitors-induced repetitive firings of muscle action
      potential. 4. Treatment with either agent resulted in nearly complete inhibitions
      of endplate potential (epp). The IC(50)s were 0.8+/-0.2 and 9+/-2 microM (n=5),
      respectively, for okadaic acid and cantharidin. On high frequency stimulation,
      the coefficient of epps was increased more than 10 fold and the extent of epp run
      down during stimulations intensified from approximately 25 to approximately 75%.
      Analyses of presynaptic quantal releases revealed decreases in epp quantal
      content and the immediately available vesicle pool. 5. The frequency of miniature
      epp was initially elevated up to 2 fold then suppressed down to approximately
      30%. The small reduction in the amplitude was antagonized when the membrane of
      endplate area was repolarized. 6. The data suggest that okadaic acid and
      cantharidin inhibit mobilizations of synaptic vesicles and depress Ca(2+) release
      from sarcoplasmic reticulum and that protein phosphatases participate in the
      modulation of motor function.

PMID- 10903959
TI  - Effects of riluzole on electrically evoked neurotransmitter release.
AB  - 1. The main purpose of the present study was to investigate the effects of the
      neuroprotective agent riluzole on the electrically evoked release of [(3)H]
      glutamate ([(3)H]-Glu) in mouse neocortical slices. The reported selectivity of
      riluzole for excitatory amino acids was tested in release experiments with
      further neurotransmitters. Also distinct species, mouse, rat and man were
      compared. 2. [(3)H]-Glu was formed endogenously during incubation of slices with
      [(3)H]-glutamine ([(3)H]-Gln). Released [(3)H]-Glu and tissue [(3)H]-Glu was
      separated by anion exchange chromatography. Electrically evoked [(3)H]-Glu
      release was strongly diminished by tetrodotoxin (TTX) and Ca(2+)-withdrawal. 3.
      Riluzole (100 microM) depressed the release of [(3)H]-Glu up to 77% (IC(50)=19.5
      microM). Riluzole was also able to inhibit strongly the electrically evoked
      release of [(3)H]-acetylcholine ([(3)H]-ACh) (at 100 microM by 92%, IC(50)=3.3
      microM, and [(3)H]-dopamine ([(3)H]-DA) (at 32 microM by 72%, IC(50)=6.8 microM).
      However, the release of [(3)H]-serotonin ([(3)H]-5-HT) was less diminished (at
      100 microM by 53%, IC(50)=39.8 microM). Riluzole up to 100 microM did not affect
      [(3)H]-noradrenaline ([(3)H]-NA) release. 4. Between species, i.e. in mouse, rat
      and human neocortex, no significant differences between the effects of riluzole
      could be observed. 5. The NMDA-receptor blocker MK-801 (1 microM) and the
      AMPA/Kainate-receptor blocker NBQX (1 microM) did neither affect the electrically
      evoked [(3)H]-ACh release nor its inhibition by riluzole, indicating that effects
      of riluzole on transmitter release were neither due to modulation of ionotropic
      Glu receptors, nor due to indirect inhibition of Glu release through these
      receptors. 6. Taken together, riluzole inhibits the release of distinct
      neurotransmitters differently, but is not selective for the excitatory amino acid
      Glu.

PMID- 10903958
TI  - Beneficial effects of n-acetylcysteine on ischaemic brain injury.
AB  - 1. Nitric oxide (NO), peroxynitrite, formed from NO and superoxide anion, poly
      (ADP-ribole) synthetase have been implicated as mediators of neuronal damage
      following focal ischaemia. Here we have investigated the effects of n
      acetylcysteine (NAC) treatment in Mongolian gerbils subjected to cerebral
      ischaemia. 2. Treatment of gerbils with NAC (20 mg kg(-1) 30 min before
      reperfusion and 1, 2 and 6 h after reperfusion) reduced the formation of post
      ischaemic brain oedema, evaluated by water content. 3. NAC also attenuated the
      increase in the brain levels of malondialdehyde (MDA) and the increase in the
      hippocampus of myeloperoxidase (MPO) caused by cerebral ischaemia. 4. Positive
      staining for nitrotyrosine was found in the hippocampus in Mongolian gerbils
      subjected to cerebral ischaemia. Hippocampus tissue sections from Mongolian
      gerbils subjected to cerebral ischaemia also showed positive staining for poly
      (ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and for
      PARS were markedly reduced in tissue sections obtained from animals that received
      NAC. 5. NAC treatment increased survival and reduced hyperactivity linked to
      neurodegeneration induced by cerebral ischaemia and reperfusion. 6. Histological
      observations of the pyramidal layer of CA1 showed a reduction of neuronal loss in
      animals that received NAC. 7. These results show that NAC improves brain injury
      induced by transient cerebral ischaemia.

PMID- 10903960
TI  - Role of inflammatory mediators in lipid A analogue (ONO-4007)-induced vascular
      permeability change in mouse skin.
AB  - 1. Endotoxin shock is accompanied by an increase in peripheral vascular
      permeability. It has been postulated that most biological activities of LPS are
      derived from lipid A moiety. Here we examined the effect of lipid A analogue ONO
      4007 in increasing vascular permeability and the possible mediators in mouse skin
      by a dye leakage method. 2. Subcutaneous injection of ONO-4007 (1 - 2 mg site(
      1)) induced a dose-dependent increase in vascular permeability which was evident
      after 120 min. 3. ONO-4007-induced dye leakage was significantly attenuated by
      pretreatments with anti-tumour necrosis factor-alpha (TNF-alpha) and anti
      interleukin-1alpha (IL-1alpha) antibodies, but not with indomethacin (5 mg kg(
      1)) or diphenhydramine (10 mg kg(-1)). ONO-4007-induced dye leakage was
      significantly inhibited by a pretreatment with N(G)-nitro-L-arginine methyl ester
      (L-NAME) (10 mg kg(-1)) but not with aminoguanidine (50 mg kg(-1)). In inducible
      nitric oxide synthase (iNOS)-deficient mice, ONO-4007 significantly increased the
      dye leakage, while ONO-4007 dilated rat thoracic aortic rings pre-contracted with
      phenylephrine, and the L-NAME pretreatment inhibited the dilation. 4. Thus, TNF
      alpha, IL-1alpha and constitutive NOSs-derived nitric oxide but not
      prostaglandins or histamine play a role in ONO-4007-induced increase in vascular
      permeability. Although ONO-4007 mimics LPS in increasing vascular permeability,
      mechanisms of permeability change elicited by ONO-4007 were not identical to
      those of LPS.

PMID- 10903961
TI  - Effect of cytochrome P-450 inhibitors econazole, bifonazole and clotrimazole on
      prostanoid formation.
AB  - 1. The present study was carried out to clarify the effect of the imidazole
      antimycotics econazole, bifonazole and clotrimazole on prostanoid biosynthesis.
      Osteoblast-like MC3T3-E1 cells stimulated by endothelin-1, melittin, ionomycin or
      arachidonic acid showed diminished prostaglandin E(2) (PGE(2)) production upon
      pretreatment with econazole. Following pretreatment with bifonazole, stimulation
      with ionomycin or arachidonic acid also resulted in decreased PGE(2) formation.
      Clotrimazole inhibited ionomycin but not arachidonic acid stimulated PGE(2)
      synthesis in MC3T3-E1 cells. 2. The results observed in osteoblast-like UMR-106
      cells pretreated with econazole, bifonazole or clotrimazole and stimulated by
      arachidonic acid were similar with the exception of clotrimazole which was a more
      effective inhibitor of PGE(2) biosynthesis than in MC3T3-E1 cells. 3. Upon
      treatment with arachidonic acid thromboxane B(2) (TXB(2)) production in human
      platelets was abolished completely at concentrations of the three imidazole
      antimycotics higher than 5 microM (IC(50)<1 microM). 4. These data were confirmed
      by a direct assay using purified ram seminal vesicle prostaglandin H(2) synthase
      1 (PGHS-1), which clearly showed inhibitory properties of econazole (IC(50) 4.7+/
      2.3 microM), bifonazole (IC(50) 9.4+/-0.8 microM) and clotrimazole (IC(50) 4.4+/
      0.6 microM). 5. Summarizing, these results indicate an inhibitory effect of
      econazole, bifonazole and clotrimazole on PGHS-1, varying in its potency
      dependent on the cell system used. In addition TXB(2) formation is affected at
      doses even lower than those needed to suppress PGE(2) biosynthesis.

PMID- 10903962
TI  - The emetic and anti-emetic effects of the capsaicin analogue resiniferatoxin in
      Suncus murinus, the house musk shrew.
AB  - 1. In SUNCUS: murinus the ultrapotent capsaicin analogue resiniferatoxin (RTX)
      induced an emetic response in the dose range 1 - 1000 microg kg(-1), s.c. The
      latency was inversely related to dose and ranged from 41.2+/-4.4 min. (1 microg
      kg(-1), s.c.) to 2.7+/-0.6 min. (1000 microg kg(-1), s.c.). 2. The emetic
      response to RTX (10 or 100 microg kg(-1), s.c.) was blocked or markedly reduced
      by pre-treatment with RTX (100 microg kg(-1), s.c.), 8-OH-DPAT (100 microg kg(
      1), s.c.), morphine (2 mg kg(-1), s.c.), neonatal capsaicin (100 mg kg(-1), s.c.)
      and the NK(1) receptor antagonist CP-99,994 (10 - 20 mg kg(-1), s.c.) but not by
      the 5-HT(3) receptor antagonist tropisetron (200 microg kg(-1), s.c.). 3. RTX
      (100 microg kg(-1), s.c.) induced c-fos-like immunoreactivity in the area
      postrema and parts of the nucleus tractus solitarius. This pattern is consistent
      with the proposal that the emetic effect is mediated via one or both of these
      structures and an involvement of substance P is discussed. 4. RTX (10 and 100
      microg kg(-1), s.c.) had broad-spectrum antiemetic effects in Suncus as indicated
      by its ability to block or markedly reduce the emetic response to motion (1 Hz, 4
      cm lateral, 10 min.), cisplatin (20 mg kg(-1), i.p.), intragastric copper
      sulphate (40 mg kg(-1), p.o.), nicotine (10 mg kg(-1), s.c.) and RTX (100 microg
      kg(-1), s.c.) itself. 5. It is proposed that the site of the anti-emetic effect
      is in the nucleus tractus solitarius and mechanisms involving the modulation of
      substance P release are discussed. 6. The general utility of SUNCUS: for
      investigations of vanilloid receptors is reviewed in the light of the exquisite
      sensitivity of the emetic reflex in this species to resiniferatoxin.

PMID- 10903963
TI  - Sodium reabsorption in thick ascending limb of Henle's loop: effect of potassium
      channel blockade in vivo.
AB  - 1. Based on previous in vitro studies, inhibition of K(+) recycling in thick
      ascending limb (TAL) is expected to lower Na(+) reabsorption through (i) reducing
      the luminal availability of K(+) to reload the Na(+)-2Cl(-)-K(+) cotransporter
      and (ii) diminishing the lumen positive transepithelial potential difference
      which drives paracellular cation transport. 2. This issue was investigated in
      anaesthetized rats employing microperfusion of Henle's loop downstream from late
      proximal tubular site with K(+)-free artificial tubular fluid in nephrons with
      superficial glomeruli. 3. The unselective K(+) channel blocker Cs(+) (5 - 40 mM)
      dose-dependently increased early distal tubular delivery of fluid and Na(+) with
      a maximum increase of approximately 20 and 185%, respectively, indicating
      predominant effects on water-impermeable TAL. 4. The modest inhibition of Na(+)
      reabsorption in response to the 15 mM of Cs(+) but not the enhanced inhibition by
      20 mM Cs(+) was prevented by luminal K(+) supplementation. Furthermore,
      pretreatment with 20 mM Cs(+) did not attenuate the inhibitory effect of
      furosemide (100 microM) on Na(+)-2Cl(-)-K(+) cotransport. 5. Neither inhibitors
      of large (charybdotoxin 1 microM) nor low (glibenclamide 250 microM; U37883A 100
      microM) conductance K(+) channels altered loop of Henle fluid or Na(+)
      reabsorption. 6. The intermediate conductance K(+) channel blockers verapamil and
      quinine (100 microM) modestly increased early distal tubular Na(+) but not fluid
      delivery, indicating a role for this K(+) channel in Na(+) reabsorption in TAL.
      As observed for equieffective concentrations of Cs(+) (15 mM), Na(+) reabsorption
      was preserved by K(+) supplementation. 7. The results indicate that modest
      inhibition of K(+) channels lowers the luminal availability of K(+) and thus
      transcellular Na(+) reabsorption in TAL. More complete inhibition lowers
      paracellular Na(+) transport probably by reducing or even abolishing the lumen
      positive transepithelial potential difference. Under the latter conditions,
      transcellular Na(+) transport may be restored by paracellular K(+) backleak.

PMID- 10903964
TI  - Mutational analysis of the interaction of the N- and C-terminal ends of
      angiotensin II with the rat AT(1A) receptor.
AB  - 1. The role of different residues of the rat AT(1A) receptor in the interaction
      with the N- and C-terminal ends of angiotensin II (AngII) was studied by
      determining ligand binding and production of inositol phosphates (IP) in COS-7
      cells transiently expressing the following AT(1A) mutants: T88H, Y92H, G196I,
      G196W and D278E. 2. G196W and G196I retained significant binding and IP
      production properties, indicating that bulky substituents in position 196 did not
      affect the interaction of AngII's C-terminal carboxyl with Lys(199) located three
      residues below. 3. Although the T88A mutation did not affect binding, the T88H
      mutant had greatly decreased affinity for AngII, suggesting that substitution of
      Thr(88) by His might hinder binding through an indirect effect. 4. The Y92H
      mutation caused loss of affinity for AngII that was much less pronounced than
      that reported for Y92A, indicating that His in that position can fulfil part of
      the requirements for binding. 5. Replacing Asp(278) by Glu caused a much smaller
      reduction in affinity than replacing it by Ala, indicating the importance of
      Asp's beta-carboxyl group for AngII binding. 6. Mutations in residues Thr(88),
      Tyr(92) and Asp(278) greatly reduced affinity for AngII but not for Sar(1) Leu(8)
      AngII, suggesting unfavourable interactions between these residues and AngII's
      aspartic acid side-chain or N-terminal amino group, which might account for the
      proposed role of the N-terminal amino group of AngII in the agonist-induced
      desensitization (tachyphylaxis) of smooth muscles.

PMID- 10903965
TI  - Involvement of central opioid systems in human interferon-alpha induced
      immobility in the mouse forced swimming test.
AB  - 1. We investigated the mechanism by which human interferon-alpha (IFN-alpha)
      increases the immobility time in a forced swimming test, an animal model of
      depression. 2. Central administration of IFN-alpha (0.05 - 50 IU per mouse,
      i.cist.) increased the immobility time in the forced swimming test in mice in a
      dose-dependent manner. 3. Neither IFN-beta nor -gamma possessed any effect under
      the same experimental conditions. 4. Pre-treatment with an opioid receptor
      antagonist, naloxone (1 mg kg(-1), s.c.) inhibited the prolonged immobility time
      induced by IFN-alpha (60 KIU kg(-1), i.v. or 50 IU per mouse. i.cist. ). 5.
      Peripheral administration of naloxone methiodide (1 mg kg(-1), s. c.), which does
      not pass the blood - brain barrier, failed to block the effect of IFN-alpha,
      while intracisternal administration of naloxone methiodide (1 nmol per mouse)
      completely blocked. 6. The effect of IFN-alpha was inhibited by a mu(1)-specific
      opioid receptor antagonist, naloxonazine (35 mg kg(-1), s.c.) and a mu(1)/mu(2)
      receptor antagonist, beta-FNA (40 mg kg(-1), s.c.). A selective delta-opioid
      receptor antagonist, naltrindole (3 mg kg(-1), s.c.) and a kappa-opioid receptor
      antagonist, nor-binaltorphimine (20 mg kg(-1), s.c.), both failed to inhibit the
      increasing effect of IFN-alpha. 7. These results suggest that the activator of
      the central opioid receptors of the mu(1)-subtype might be related to the
      prolonged immobility time of IFN-alpha, but delta and kappa-opioid receptors most
      likely are not involved.

PMID- 10903966
TI  - Inotropic response to endothelin-1, isoprenaline and calcium in cardiomyocytes
      isolated from endotoxin treated rats: effects of ethyl-isothiourea and
      dexamethasone.
AB  - 1. The contractile effects of endothelin-1, isoprenaline and extracellular
      calcium were assessed on ventricular cardiomyocytes isolated from
      lipopolysaccharide-treated rats. The involvement of nitric oxide was investigated
      using dexamethasone (in vivo) and ethyl isothiourea (in vitro). 2. Male Wistar
      rats (n=70) were injected with either saline (1 ml kg(-1)) or lipopolysaccharide
      (LPS; 5 mg kg(-1)) alone, or following pre-treatment with dexamethasone (DEX+LPS;
      5 mg kg(-1)). Ventricular cell shortening was recorded using a video edge
      detection system, and concentration-response relationships were established for
      endothelin-1, isoprenaline and calcium, in the absence or presence of ethyl
      isothiourea (ETU; 10 microM). iNOS expression was assessed using reverse
      transcription-polymerase chain reaction. 3. iNOS mRNA expression was greater
      (P<0.001) in the LPS (iNOS/GAPDH ratio: 0.90+/-0.09) treated group compared to
      saline (iNOS/GAPDH ratio: 0.36+/-0.02). Baseline contractile amplitude was
      reduced (P<0.05) in the LPS (7.3+/-0.2 microm) and DEX+LPS groups (6.7+/-0.3
      microm) compared to saline (8. 0+/-0.2 microm). 4. The concentration-dependent
      contractile response to endothelin-1 was attenuated (P<0.05) in the LPS group
      compared to saline (maximum change: 0.45+/-0.2 vs 1.8+/-0.2 microm). Neither ETU
      nor dexamethasone improved contractile function in the LPS-treated animals. 5.
      The concentration-dependent increase in the contractile response to isoprenaline
      was attenuated in the LPS-treated group compared to saline (P<0.05; maximum
      change: 1.7+/-0.4 vs 3.1+/-0.4 microm). This effect was reversed by ETU (maximum
      change: 3.7+/-0.6 microm). Pre-treatment with dexamethasone prevented a
      significant fall in contraction amplitude (maximum change: 2.4+/-0.4 microm). 6.
      The contractile response to calcium was reduced (P<0.05) in the LPS group
      compared to saline (maximum change: 8.7+/-0.6 vs 10.7+/-0.8 microm). Neither ETU
      nor dexamethasone restored contractile function in the LPS-treated group. 7. In
      conclusion, a nitric oxide-mediated inhibitory pathway is not responsible for the
      diminished contractile response to either endothelin-1 or extracellular calcium,
      but contributes to the hyporesponsiveness to isoprenaline in lipopolysaccharide
      treated rats.

PMID- 10903968
TI  - YD-3, a novel inhibitor of protease-induced platelet activation.
AB  - 1. In the present study, the antiplatelet effects and mechanisms of a new
      synthetic compound YD-3 [1-benzyl-3(ethoxycarbonylphenyl)-indazole] were
      examined. 2. YD-3 inhibited the aggregation of washed rabbit platelets caused by
      thrombin (IC(50)=28.3 microM), but had no or little inhibitory effect on that
      induced by arachidonic acid, collagen, platelet-activating factor (PAF) or
      U46619. YD-3 also suppressed generation of inositol phosphates caused by
      thrombin. On the other hand, thrombin-induced fibrin formation was not affected
      by YD-3, indicating YD-3 does not inhibit the proteolytic activity of thrombin.
      3. In washed human platelets, however, YD-3 had only mild inhibitory effect on
      the low concentration (0.05 u ml(-1)) of thrombin-induced human platelet
      aggregation, and did not affect that induced by higher concentrations (> or =0.1
      u ml(-1)) of thrombin or SFLLRN, the protease-activated receptor 1 (PAR1) agonist
      peptide. By contrast, YD-3 inhibited both human and rabbit platelet aggregation
      elicited by trypsin with IC(50) values of 38.1 microM and 5.7 microM,
      respectively. 4. YD-3, at 100 microM, had no effect on ristocetin-induced
      glycoprotein Ib (GPIb)-dependent aggregation of human platelets. In addition,
      platelets treated with chymotrypsin, which cleaves GPIb, enhanced rather than
      attenuated the inhibition of YD-3 on thrombin-induced human platelet aggregation.
      These data indicate that GPIb plays no role in the antiplatelet effect of YD-3.
      5. In SFLLRN-desensitized human platelets, high concentration of thrombin (1 u
      ml(-1)) could still elicit intracellular Ca(2+) mobilization, and the rise of
      [Ca(2+)](i) was prevented by either leupeptin or YD-3. 6. Our results suggest
      that YD-3 inhibits a non-PAR1 thrombin receptor which mediates the major effect
      of thrombin in rabbit platelets, but in human platelets, this receptor function
      becomes significant only when the function of PAR1 has been blocked or
      attenuated.

PMID- 10903967
TI  - Role of central glutamate receptors, nitric oxide and soluble guanylyl cyclase in
      the inhibition by endotoxin of rat gastric acid secretion.
AB  - 1. This study examines the role of a central pathway involving glutamate
      receptors, nitric oxide (NO) and cyclic GMP in the acute inhibitory effects of
      low doses of peripheral endotoxin on pentagastrin-stimulated acid production. 2.
      Vagotomy or intracisternal (i.c.) microinjections of the NO-inhibitor, N(G)-nitro
      L-arginine methyl esther (L-NAME; 200 microg rat(-1)) restored acid secretory
      responses in endotoxin (10 microg kg(-1), i.v.)-treated rats. 3. The acid
      inhibitory effect of i.v. endotoxin (10 microg kg(-1), i.v.) was prevented by
      prior i.c. administration of the NMDA receptor antagonists, dizocilpine maleate
      (MK-801; 10 nmol rat(-1)) and D-2-amino-5-phosphono-valeric acid (AP-5; 20 nmol
      rat(-1)), or the AMPA/kainate antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX;
      10 nmol rat(-1)). However, the competitive metabotropic glutamate receptor
      antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; 20 - 1000 nmol rat(-1))
      did not antagonize the effects of endotoxin. 4. I.c. administration of L
      glutamate (0.1 nmol rat(-1)) inhibited pentagastrin-stimulated gastric acid
      secretion. Coadministration with L-NAME (200 microg rat(-1)) prevented the
      inhibition of gastric acid secretion by the aminoacid. 5. I.c. administration of
      1H-[1,2, 4]Oxazodiolo[4,3-a]quinoxalin-1-one (ODQ; 100 nmol rat(-1)), a soluble
      guanylyl cyclase (sGC) blocker, reversed the hyposecretory effect of endotoxin.
      6. I.c. administration of the cyclic GMP analogue 8-Bromoguanosine-3,5-cyclic
      monophosphate (8-Br-cGMP; 100 - 300 nmol rat(-1)) reduced gastric acid production
      in a dose-dependent manner. 7. We conclude that central NMDA and AMPA/kainate
      receptors are involved in the acid inhibitory effect of peripherally administered
      endotoxin. This central pathway involves synthesis of NO, which acts on the
      enzyme sGC.

PMID- 10903969
TI  - Effects of combined neutral endopeptidase 24-11 and angiotensin-converting enzyme
      inhibition on femoral vascular conductance in streptozotocin-induced diabetic
      rats.
AB  - 1. The successive effects of the angiotensin-converting enzyme inhibitor
      captopril (CAP, 2 mg kg(-1)+1 mg kg(-1) 30 min(-1) infusion) and the neutral
      endopeptidase 24-11 inhibitor retrothiorphan (RT, 25 mg kg(-1)+12.5 mg kg(-1) 30
      min(-1) infusion) were studied on femoral vascular conductance (FVC) in
      streptozotocin-induced diabetic (STZ-SD) and control Sprague-Dawley (C-SD) rats.
      The role of the kinin-nitric oxide (NO) pathway was assessed by (1) using pre
      treatments: a bradykinin (BK) B2 receptor antagonist (Hoe-140, 300 microg kg(
      1)), a NO-synthase inhibitor (N(omega)-nitro-L-arginine methyl ester, L-NAME, 10
      mg kg(-1)), a kininase I inhibitor (DL-2-mercaptomethyl-3
      guanidinoethylthiopropanoic acid, MGTA, 10 mg kg(-1)+20 mg kg(-1) 20 min(-1)
      infusion) and (2) comparing the effects in STZ-induced diabetic (STZ-BN) and
      control Brown-Norway kininogen-deficient (C-BN) rats. 2. In C-SDs, CAP and CAP+RT
      increased FVC similarly. In STZ-SDs, FVC and FBF were decreased compared to C
      SDs. CAP+RT increased them more effectively than CAP alone. 3. In both C-SDs and
      STZ-SDs, the femoral bed vasodilatation elicited by CAP was inhibited by Hoe-140
      and L-NAME. The FVC increase elicited by CAP+RT was not significantly reduced by
      Hoe-140 but was inhibited by L-NAME and Hoe-140+MGTA. 4. In C-BNs, the
      vasodilatator responses to CAP and CAP+RT were abolished and highly reduced,
      respectively. In STZ-BNs, these responses were abolished. 5. These results show
      that in STZ-SDs, CAP+RT improve FBF and FVC more effectively than CAP alone.
      These effects are linked to an increased activation of the kinin-NO pathway. BK
      could lead to NO production by BK B2 receptor activation and another pathway in
      which kininase I may be involved.

PMID- 10903970
TI  - Comparative effects of continuous infusion of mCPP, Ro 60-0175 and d-fenfluramine
      on food intake, water intake, body weight and locomotor activity in rats.
AB  - 1. The aim of the study was to compare the effects of 14 day subcutaneous
      infusion of the 5-HT(2C) receptor agonists, m-chlorophenylpiperazine (mCPP, 12 mg
      kg(-1) day(-1)) and Ro 60-0175 (36 mg kg(-1) day(-1)) and the 5-HT releasing
      agent and re-uptake inhibitor, d-fenfluramine (6 mg kg(-1) day(-1)), on food and
      water intake, body weight gain and locomotion in lean male Lister hooded rats. 2.
      Chronic infusion of all three drugs significantly reduced food intake and
      attenuated body weight gain. In contrast, drug infusion did not lead to
      significant reductions in locomotor activity in animals assessed 2 and 13 days
      after pump implantation. 3. In a subsequent 14 day study that was designed to
      identify possible tolerance during days 7 - 14, animals were given a subcutaneous
      infusion of mCPP (12 mg kg(-1) day(-1)) or d-fenfluramine (6 mg kg(-1) day(-1))
      for either 7 or 14 days. During the first 7 days both drugs significantly reduced
      body weight gain compared to saline-infused controls; however, from day 7 onwards
      animals withdrawn from drug treatment exhibited an increase in body weight such
      that by day 14 they were significantly heavier than their 14-day drug-treated
      counterparts. 4. Both mCPP and d-fenfluramine reduced daily food intake
      throughout the infusion periods. For 14-day treated animals this hypophagia was
      marked during the initial week of the study but only minor during the second
      week. In light of the sustained drug effect on body weight, the data suggest that
      weight loss by 5-HT(2C) receptor stimulation may be only partly dependent on
      changes in food consumption and that 5-HT(2C) receptor agonists may have effects
      on thermogenesis. 5. These data suggest tolerance does not develop to the effects
      of d-fenfluramine, mCPP and Ro 60-0175 on rat body weight gain.

PMID- 10903972
TI  - Voltage-dependent blockade of normal and mutant muscle sodium channels by
      benzylalcohol.
AB  - 1. We studied the effects of benzylalcohol on heterologously expressed wild type
      (WT), paramyotonia congenita (R1448H) and hyperkalaemic periodic paralysis
      (M1360V) mutant alpha-subunits of human skeletal muscle sodium channels. 2.
      Benzylalcohol blocked rested channels at -150 mV membrane potential, with an
      ECR(50) of 5.3 mM in wild type, 5.1 mM in R1448H, and 6.2 mM in M1360V. When
      blockade was assessed at -100 mV, the ECR(50) was reduced in R1448H (2 mM)
      compared with both wild type (4.3 mM; P<0.01) and M1360V (4.3 mM). 3. Membrane
      depolarization before the test depolarization significantly promoted
      benzylalcohol-induced sodium channel blockade. The values of K(D) for the fast
      inactivated state derived from benzylalcohol-induced shifts in steady-state
      availability curves were 0.66 mM in wild type and 0.58 mM in R1448H. In the
      presence of slow inactivation induced by 2.5 s depolarizing prepulses, the
      ECI(50) for benzylalcohol-induced current inhibition was 0.59 mM in wild type and
      0.53 mM in R1448H. 4. Recovery from fast inactivation was prolonged in the
      presence of drug in all clones. 5. Benzylalcohol induced significant frequency
      dependent block at stimulating frequencies of 10, 50, and 100 Hz in all clones.
      6. Our results clearly show that benzylalcohol is an effective blocker of muscle
      sodium channels in conditions that are associated with membrane depolarization.
      Mutants that enter voltage-dependent inactivation at more hyperpolarized membrane
      potentials compared with wild type are more sensitive to inhibitory effects at
      the normal resting potential.

PMID- 10903971
TI  - Effects of dronedarone on acetylcholine-activated current in rabbit SAN cells.
AB  - 1. The effect of the antiarrhythmic drug dronedarone on the Acetylcholine
      activated K(+) current (I(K(ACh))) was investigated in single cells isolated from
      sinoatrial node (SAN) tissue of rabbit hearts. 2. Externally perfused dronedarone
      (0.001 - 1 microM) caused a potent, voltage independent block of I(K(ACh)).
      Fitting of the dose response curve of I(K(ACh)) block yielded an IC(50) value of
      63 nM, a value over one order of magnitude lower than those reported for
      dronedarone block of other cardiac currents. 3. I(K(ACh)) block was not due to an
      inhibitory action of dronedarone on the muscarinic M2 receptor activation, since
      the drug was effective on I(K(ACh)) constitutively activated by intracellular
      perfusion with GTP-gammaS. 4. External cell perfusion with dronedarone inhibited
      the activity of I(K(ACh)) channels recorded from cell-attached patches by
      reducing the channel open probability (from 0.56 to 0.11) without modification of
      the single-channel conductance. 5. These data suggest that dronedarone blocks
      I(K(ACh)) channels either by disrupting the G-protein-mediated activation or by a
      direct inhibitory interaction with the channel protein.

PMID- 10903973
TI  - Cytoplasmic binding and disposition kinetics of diclofenac in the isolated
      perfused rat liver.
AB  - 1. The binding kinetics of diclofenac to hepatocellular structures were evaluated
      in the perfused rat liver using the multiple indicator dilution technique and a
      stochastic model of organ transit time density. 2. The single-pass, in situ rat
      liver preparation was perfused with buffer solution (containing 2% albumin) at 30
      ml min(-1). Diclofenac and [(14)C]-sucrose (extracellular reference) were
      injected simultaneously as a bolus dose into the portal vein (six experiments in
      three rats). An analogous series of experiments was performed with [(14)C]
      diclofenac and [(3)H]-sucrose. 3. The diclofenac outflow data were analysed using
      three models of intracellular distribution kinetics, assuming (1) instantaneous
      distribution and binding (well-mixed model), (2) 'slow' binding at specific
      intracellular sites after instantaneous distribution throughout the cytosol (slow
      binding model), and (3) 'slowing' of cytoplasmic diffusion due to instantaneous
      binding (slow diffusion model). 4. The slow binding model provided the best
      description of the data. The rate constants for cellular influx and sequestration
      were 0.126+/-0. 026 and 0.013+/-0.009 s(-1), respectively. The estimated ratio of
      cellular initial distribution volume to extracellular volume of 2.82 indicates an
      almost instantaneous distribution in the cellular water space, while the
      corresponding ratio of 5.54 estimated for the apparent tissue distribution volume
      suggests a relatively high hepatocellular binding. The non-instantaneous
      intracellular equilibration process was characterized by time constants of the
      binding and unbinding process of 53.8 and 49.5 s, respectively. The single-pass
      availability of diclofenac was 86%. The results obtained with [(14)C]-diclofenac
      and [(3)H]-sucrose were not statistically different.

PMID- 10903975
TI  - [(3)H]-8-OH-DPAT binding in the rat brain raphe area: involvement of 5-HT(1A) and
      non-5-HT(1A) receptors.
AB  - 1. The 5-HT(1A) agonist 8-OH-DPAT has been shown to have additional 5-HT uptake
      inhibiting properties. The present work was undertaken to examine further the
      binding of [(3)H]-8-OH-DPAT in the raphe area of the rat brain, a region rich in
      5-HT(1A) receptors and 5-HT uptake sites. 2. 5-HT inhibited [(3)H]-8-OH-DPAT
      binding in a biphasic manner (pK(i1): 8.82+/-0.01, pK(i2): 6.07+/-0.05, n=4) with
      the low affinity site representing 36+/-4% of the total population. A biphasic
      inhibition curve was found also with the 5-HT(1A) antagonist, WAY 100635 (pK(i1):
      8.65+/-0.17, pK(i2): 4.26+/-0.38, n=3). In the presence of 1 microM WAY 100635 to
      mask 5-HT(1A) receptors, 5-HT inhibited [(3)H]-8-OH-DPAT binding in a monophasic
      manner (pK(i): 6.04+/-0.07, n=3). 3. The affinities of various compounds for
      sites labelled by [(3)H]-8-OH-DPAT in the presence of 1 microM WAY 100635 and for
      sites labelled by [(3)H]-citalopram (a selective 5-HT uptake inhibitor) were
      determined. There was a significant correlation between pK(i) values at 5-HT
      uptake sites and at non-5HT(1A) sites labelled by [(3)H]-8-OH-DPAT (r=0.80, P<0.
      001, n=17), suggesting these latter sites to be 5-HT uptake sites. 4. Whereas the
      affinities of R(+) and S(-) enantiomers of 8-OH-DPAT for the 5-HT uptake site are
      similar, R(+)8-OH-DPAT has 10 times higher affinity for the non-5-HT(1A) site
      than S(-)8-OH-DPAT and was considered as an outlier in the correlation. It is
      suggested that [(3)H]-8-OH-DPAT labels other, as yet unknown binding sites in the
      raphe.

PMID- 10903974
TI  - Comparison of enalapril and valsartan in cyclosporine A-induced hypertension and
      nephrotoxicity in spontaneously hypertensive rats on high-sodium diet.
AB  - 1. We compared the effects of the angiotensin converting enzyme (ACE) inhibitor
      enalapril and the angiotensin AT(1) receptor antagonist valsartan in cyclosporine
      A (CsA)-induced hypertension and nephrotoxicity in spontaneously hypertensive
      rats (SHR). 2. SHR (8 - 9 weeks old) on high-sodium diet were given CsA (5 mg kg(
      1)d (-1) s.c. ) for 6 weeks. The rats were treated concomitantly either with
      enalapril (30 mg kg(-1)d (-1) p.o.) or valsartan (3 or 30 mg kg(-1) d (-1) p.o.).
      To evaluate the role of bradykinin in the action of enalapril, some rats received
      a bradykinin B(2) receptor antagonist icatibant (HOE 140, 500 microg kg(-1) d (
      1) s.c.) during the last 2 weeks of enalapril treatment. 3. Blood pressure was
      recorded every second week by tail cuff method. Renal function was measured by
      serum creatinine, creatinine clearance and urinary excretion of proteins at the
      end of the experiment. The activity of the renal kallikrein-kinin system was
      estimated by urinary kallikrein excretion. 4. CsA caused hypertension, impaired
      renal function and induced morphological nephrotoxicity with glomerular damage
      and interstitial fibrosis. Enalapril and the lower dose of valsartan attenuated
      the CsA-induced hypertension to the same extent, while the higher dose of
      valsartan totally abolished it. Icatibant did not reduce the antihypertensive
      effect of enalapril. Urinary kallikrein excretion was similar in all groups. 5.
      Enalapril and valsartan equally prevented the CsA-induced deterioration of kidney
      function and morphology. 6. The renin-angiotensin but not the kallikrein-kinin
      system plays a crucial role in CsA-toxicity during high intake of sodium in SHR.

PMID- 10903976
TI  - The MAP kinase inhibitors, PD098059, UO126 and SB203580, inhibit IL-1beta
      dependent PGE(2) release via mechanistically distinct processes.
AB  - 1. In common with human bronchial epithelial cells, pulmonary A549 cells release
      prostaglandin (PG) E(2) in response to pro-inflammatory cytokines. We have
      therefore used these cells to examine the effect of the selective mitogen
      activated protein (MAP) kinase inhibitors; PD098059, a mitogen activated and
      extracellular regulated kinase kinase (MEK) 1 inhibitor, UO126, a dual MEK1 &
      MEK2 inhibitor, and SB203580, a p38 MAP kinase inhibitor in the IL-1beta
      dependent release of PGE(2). 2. Following IL-1beta treatment the extracellular
      regulated kinases (ERKs) and the p38 MAP kinases were rapidly phosphorylated. 3.
      PD09059, UO126 and SB203580 prevented IL-1beta-induced PGE(2) release at doses
      that correlated closely with published IC(50) values. Small or partial effects at
      the relevant doses were observed on induction of cyclo-oxygenase (COX) activity
      or COX-2 protein suggesting that the primary effects were at the level of
      arachidonate availability. 4. Neither PD098059 nor SB203580 showed any effect on
      IL-1beta-induced arachidonate release. We therefore speculate that the MEK1/ERK
      and p38 kinase cascades play a role in the functional coupling of arachidonate
      release to COX-2. 5. In contrast, UO126 was highly effective at inhibiting IL
      1beta-dependent arachidonate release, implicating MEK2 in the activation of the
      PLA(2) that is involved in IL-1beta-dependent PGE(2) release. 6. We conclude that
      the MEK1, MEK2 and p38 MAP kinase inhibitors, PD098059, UO126 and SB203580, are
      highly potent in respect of inflammatory PG release. Finally, we conclude that
      these inhibitors act via mechanistically distinct processes, which may have anti
      inflammatory benefits.

PMID- 10903977
TI  - Murine myeloid progenitor responses to GM-CSF and eosinophil precursor responses
      to IL-5 represent distinct targets for downmodulation by prostaglandin E(2).
AB  - 1. Because Prostaglandin E(2) (PGE(2)) and dibutiryl cyclic AMP (dbcAMP) modulate
      the production and effects of haemopoietic cytokines in allergy, we examined
      their ability to modulate responses of myeloid progenitors to GM-CSF, and of
      eosinophil precursors to IL-5. 2. The ability of PGE(2), dbcAMP, rolipram,
      forskolin, dbcGMP and PGD(2), to modulate the responses to GM-CSF and IL-5 in
      colony formation (progenitor) and eosinophil differentiation (precursor) assays
      using bone-marrow from nonsensitized or from intranasally-challenged, ovalbumin
      sensitized mice of five strains was studied. 3. PGE(2) (10(-7) M) inhibited GM
      CSF-stimulated colony formation in bone-marrow from BP-2 mice. This effect was
      duplicated by dbcAMP (0.3 - 1x10(-6) M), Rolipram (10(-5) M) and forskolin (3x10(
      5) M), but not Prostaglandin D(2) (10(-6) M). Inhibition affected similarly all
      myeloid colony types. Progenitors from sensitized and challenged BP-2 mice were
      also inhibited by PGE(2) and cyclic AMP. PGE(2) inhibited progenitors from
      C57BL/10, CBA/J and A/J, but not BALB/c mice. However, BALB/c progenitors were
      sensitive to dbcAMP and Forskolin (10(-4) M). In contrast, in precursor assays,
      PGE(2) (10(-7) - 10(-9) M) blocked responses to IL-5 in bone-marrow from BP-2 and
      BALB/c mice, either naive or sensitized and challenged, to a similar extent.
      PGD(2) (10(-6) M) was ineffective, as was PGE(2) (10(-7) M), if added after 48 h
      of culture. 4. In conclusion, PGE(2) inhibits the responses of bone-marrow
      myeloid progenitors to GM-CSF and of eosinophil precursors to IL-5, in naive or
      ovalbumin sensitized and challenged mice. These effects are duplicated by cyclic
      AMP-elevating agents. In the BALB/c strain, the resistance of progenitors, but
      not precursors, to PGE(2) inhibition, indicates these developmental stages are
      separate targets for PGE(2) modulation.

PMID- 10903979
TI  - Diinosine pentaphosphate: an antagonist which discriminates between recombinant
      P2X(3) and P2X(2/3) receptors and between two P2X receptors in rat sensory
      neurones.
AB  - 1. We have compared the antagonist activity of trinitrophenyl-ATP (TNP-ATP) and
      diinosine pentaphosphate (Ip(5)I) on recombinant P2X receptors expressed in
      Xenopus oocytes with their actions at native P2X receptors in sensory neurones
      from dorsal root and nodose ganglia. 2. Slowly-desensitizing responses to
      alpha,beta-methylene ATP (alpha,beta-meATP) recorded from oocytes expressing
      P2X(2/3) receptors were inhibited by TNP-ATP at sub-micromolar concentrations.
      However, Ip(5)I at concentrations up to 30 microM was without effect. 3. Nodose
      ganglion neurones responded to alpha,beta-meATP with slowly-desensitizing inward
      currents. These were inhibited by TNP-ATP (IC(50), 20 nM), but not by Ip(5)I at
      concentrations up to 30 microM. 4. In DRG neurones that responded to ATP with a
      rapidly-desensitizing inward current, the response was inhibited by TNP-ATP with
      an IC(50) of 0.8 nM. These responses were also inhibited by Ip(5)I with an IC(50)
      of 0.1 microM. Both antagonists are known to inhibit homomeric P2X(3) receptors.
      5. Some DRG neurones responded to alpha,beta-meATP with a biphasic inward
      current, consisting of transient and sustained components. While the transient
      current was abolished by 1 microM Ip(5)I, the sustained component remained
      unaffected. 6. In conclusion, Ip(5)I is a potent antagonist at homomeric P2X(3)
      receptors but not at heteromeric P2X(2/3) receptors, and therefore should be a
      useful tool for elucidating the subunit composition of native P2X receptors.

PMID- 10903978
TI  - Effect of furanocoumarin derivatives in grapefruit juice on the uptake of
      vinblastine by Caco-2 cells and on the activity of cytochrome P450 3A4.
AB  - 1. The presence of inhibitors of drug efflux transporters, such as P-glycoprotein
      (P-gp), in grapefruit juice (GFJ) was confirmed based on the uptake of [(3)H]
      vinblastine (VBL) by Caco-2 cells. 2. The uptake of [(3)H]-VBL by Caco-2 cells
      was significantly increased by the ethyl acetate extract of GFJ as well as by
      cyclosporin A. The extract was separated on a Cosmosil column and the eluate with
      60% methanol increased [(3)H]-VBL uptake, while the activity to inhibit CYP3A4
      was greatest in the 70 and 80% eluates. 3. These results show that the major
      inhibitor of efflux transport of VBL is different from that of CYP3A4. 4. Further
      separation of the 60% methanol eluate afforded dihydroxybergamottin (DHBG). Both
      ethyl acetate extract of GFJ and DHBG increased steady-state [(3)H]-VBL uptake by
      LLC-GA5-COL300 cells. Besides DHBG, other furanocoumarins contained in GFJ, such
      as bergamottin, FC726, bergaptol and bergapten, increased the steady-state uptake
      of [(3)H]-VBL by Caco-2 cells. 5. The order of inhibitory potency of these
      compounds was FC726>DHBG>bergamottin>bergapten>bergaptol . While, the IC(50)
      values for inhibition of CYP3A4 were 0.075, 0.45, 1.0, 1.0 and >20 microM,
      respectively. Bergaptol specifically inhibited VBL efflux. 6. DHBG was thus
      identified as a candidate for inhibitors of VBL transport, together with other
      furanocoumarins. Moreover, partly involvement of the P-gp inhibition was
      suggested. 7. Therefore, the inhibition of efflux transport of drugs as well as
      of drug metabolism by CYP3A4 could be an important cause of drug-GFJ interaction.

PMID- 10903980
TI  - Antidepressant drugs inhibit glucocorticoid receptor-mediated gene transcription 
      a possible mechanism.
AB  - 1. Antidepressant drugs are known to inhibit some changes evoked by
      glucocorticoids, as well as a hyperactivity of hypothalamic-pituitary-adrenal
      (HPA) axis, often observed in depression. 2. The aim of present study was to
      investigate effects of various antidepressant drugs on the glucocorticoid
      mediated gene transcription in fibroblast cells, stably transfected with an MMTV
      promoter (LMCAT cells). 3. The present study have shown that antidepressants
      (imipramine, amitriptyline, desipramine, fluoxetine, tianeptine, mianserin and
      moclobemide), but not cocaine, inhibit the corticosterone-induced gene
      transcription in a concentration- and a time-dependent manner. 4. Drugs which are
      known to augment clinical effects of medication in depressed patients (lithium
      chloride, amantadine, memantine), do not affect the inhibitory effects of
      imipramine on the glucocorticoid receptor (GR)-mediated gene transcription. 5.
      Inhibitors of phospholipase C (PLC), protein kinase C (PKC), Ca(2+)/calmodulin
      dependent protein kinase (CaMK) and antagonists of the L-type Ca(2+) channel also
      inhibit the corticosterone-induced gene transcription. 6. Inhibitors of protein
      kinase A (PKA) and protein kinase G (PKG) are without effect on the GR-induced
      gene transcription. 7. Phorbol ester (an activator of PKC) attenuates the
      inhibitory effect of imipramine on the GR-induced gene transcription. 8.
      Imipramine decreases binding of corticosterone-receptor complex to DNA. 9. It is
      concluded that antidepressant drugs inhibit the corticosterone-induced gene
      transcription, and that the inhibitory effect of imipramine depends partly on the
      PLC/PKC pathway.

PMID- 10903981
TI  - Inhibition by ethanol of rat P2X(4) receptors expressed in Xenopus oocytes.
AB  - 1. The effect of ethanol on the function of P2X(4) receptors expressed in Xenopus
      oocytes was studied using two-electrode voltage-clamp recording. 2. The amplitude
      of current activated by 1 microM ATP was decreased by ethanol in a concentration
      dependent manner over the concentration range 1 - 500 mM. The concentration of
      ethanol that produced 50% inhibition (IC(50)) of current activated by 1 microM
      ATP was 58 mM. 3. Ethanol inhibition of ATP-activated current was not dependent
      on membrane potential from -60 to +20 mV, and ethanol did not change the reversal
      potential of ATP-activated current. 4. Ethanol, 50 mM, shifted the ATP
      concentration-response curve to the right, increasing the EC(50) for ATP from 9.1
      to 16.0 microM, but did not reduce the maximal response to ATP. 5. The results
      suggest that ethanol may inhibit P2X(4) receptors by decreasing the apparent
      affinity of the binding site for ATP. 6. Since the P2X(4) receptor is the most
      abundant P2X subunit in the brain, these receptors could be important effectors
      of ethanol action in the central nervous system.

PMID- 10903982
TI  - NO-naproxen modulates inflammation, nociception and downregulates T cell response
      in rat Freund's adjuvant arthritis.
AB  - 1. Anti-inflammatory non steroidal drugs releasing NO (NO-NSAIDs) are a new class
      of anti-inflammatory drugs to which has been added an NO-releasing moiety. These
      compounds have been shown to retain the anti-inflammatory, analgesic and
      antipyretic activity of the parent compound but to be devoid of gastrointestinal
      (GI) toxicity. 2. Freund's adjuvant (FA) arthritis was induced in rats by a
      single intraplantar injection into the right hindpaw of 100 microl of
      mycobacterium butirricum (6 mg ml(-1)). The effect of equimolar doses of naproxen
      (1, 3 and 10 mg kg(-1)) and NO-naproxen (1.5, 4.5 and 16 mg kg(-1)) was evaluated
      using two dosage regimen protocols: (i) preventive, starting oral administration
      of the drugs at the time of induction of arthritis and for the following 21 days
      (day 1 - 21); (ii) therapeutic, starting oral administration of the drugs 7 days
      after adjuvant injection and for the following 14 days (day 7 - 21). 3. Hindpaw
      swelling (days 3, 7, 11, 14, 17, 21) and nociception (days 15 and 21) were
      measured. On day 22 rats were sacrificed, draining lymph nodes were removed and T
      cells isolated. In vitro proliferation of T cells following stimulation with
      concanavalin A (0.5 - 5 microg ml(-1)) was measured using a tritiated thymidine
      incorporation assay. IL-2 receptor expression on T cells was measured by FACS
      analysis. 4. Naproxen and NO-naproxen showed similar activity in reducing oedema
      formation in the non-injected (controlateral) hindpaw. Both drugs showed anti
      nociceptive effect. NO-naproxen was anti-nociceptive at a dose of 4.5 mg kg(-1)
      while naproxen showed the same extent of inhibition only at a dose of 10 mg kg(
      1). 5. T cells were isolated and characterized by FACS analysis. Stimulation of
      isolated T cells with concanavallin A in vitro caused a significant increase in
      thymidine uptake. NO-naproxen at a dose of 4.5 mg kg(-1) inhibited T cell
      proliferation to the same extent as 10 mg kg(-1) of naproxen. 6. Inhibition of T
      cell proliferation was well correlated with reduced IL-2 receptor expression on T
      cells. In addition, NO-naproxen reduced both IL-1beta and TNFalpha plasma levels
      whilst naproxen reduced IL-1beta levels only. 7. In conclusion, both naproxen and
      NO-naproxen reduce inflammation and nociception associated with arthritis. In
      addition NO-naproxen interferes to a larger extent with cellular mechanism
      involved in T cell activation in rat adjuvant arthritis indicating that
      introduction of the NO moiety in the naproxen structure increases the effect at
      the level of the immune system.

PMID- 10903983
TI  - [Ca(2+)](i)- and insulin-stimulating effect of the non-membranepermeable
      phosphatase-inhibitor microcystin-LR in intact insulin-secreting cells (RINm5F).
AB  - 1. Microcystin-LR, a specific and effective inhibitor of serine/threonine
      phosphatases type 1/2A which does not permeate cells, was used to distinguish
      intracellular and extracellular effects of phosphatase inhibitors on insulin
      secretion by RINm5F cells. 2. Incubation of intact RINm5F cells with microcystin
      LR (0.1 - 2 microM) almost doubled basal insulin release at 3 mM glucose but left
      maximal insulin release induced by KCl (30 mM) unaffected. 3. In parallel, there
      was an increase in cytosolic Ca(2+) by up to half maximum, which could be
      suppressed by the Ca(2+)-channel blocker D600. 4. In contrast, microcystin-LR
      incubation of intact cells did not affect phosphatase activity but significantly
      reduced phosphatase activity when used in cellular fractions. 5. From these data
      we conclude that microcystin-LR could affect Ca(2+)-channels and insulin release
      by inhibiting an extracellular phosphatase-like activity.

PMID- 10903984
TI  - On the mechanism of ADP-induced alteration of sulphonylurea sensitivity in
      cardiac ATP-sensitive K(+) channels.
AB  - 1. To study the mechanism of regulation of sulphonylurea sensitivity in ATP
      sensitive K(+) (K(ATP)) channels, we used the inside-out patch clamp technique in
      guinea-pig ventricular myocytes. 2. In the absence of nucleotides, the half
      maximal concentration of tolbutamide inhibition of K(ATP) channels (IC(50)) was
      0.4 mM, and it decreased to 0.1 mM when 0.1 mM ATP was added. 3. Increasing the
      ADP concentration from 0 to 0.1 and 0.3 mM in the absence of ATP shifted the
      IC(50) from 0.4 to 5.3 and 11.4 mM, respectively. Increasing the ADP
      concentration further to 1 and 3 mM conversely reduced the IC(50) to 9.5 and 4.4
      mM, respectively. 4. In the absence of Mg(2+) and ADP, the IC(50) was calculated
      to 16.6 mM which was found to be less, 12.3, 5.1 and 2.5 mM, respectively, when
      the ADP concentration was increased to 0.1, 0.3 and 1 mM. 5. The IC(50)s for
      tolbutamide obtained at various concentrations of ADP in the presence of Mg(2+)
      were best fitted by equations reflecting a model that assumed two binding sites
      for ADP; one is a high affinity site that reduces the sensitivity to the
      sulphonylurea, while the other is a low affinity site that increases such
      sensitivity. Dissociation constants calculated for ADP to sites 1 and 2 were 2.6
      microM and 46.7 mM, respectively. In the absence of Mg(2+), data were fitted by
      equations corresponding to a single site model (site 2); the dissociation
      constant for ADP was 25.0 mM. 6. It is concluded that ADP modifies tolbutamide
      sensitivity by binding to two sites. The high affinity site is strongly Mg(2+)
      dependent, whereas the low affinity site is Mg(2+)-independent.

PMID- 10903987
TI  - Smooth muscle cells : another source of tissue factor-containing microparticles
      in atherothrombosis?

PMID- 10903985
TI  - Cytokine-mediated inflammatory hyperalgesia limited by interleukin-1 receptor
      antagonist.
AB  - 1. The effect of IL-1ra on response to intraplantar (i.pl.) injection of LPS,
      carrageenin, bradykinin, TNFalpha, IL-1beta, IL-8, PGE(2) and dopamine was
      investigated in a model of mechanical hyperalgesia in rats. 2. IL-1ra inhibited
      hyperalgesic response to LPS, carrageenin, bradykinin, TNFalpha, and IL-1beta,
      but not responses to IL-8, PGE(2) and dopamine. 3. A sheep anti-rat IL-1ra serum
      potentiated response to LPS, carrageenin, bradykinin, TNFalpha and IL-1beta but
      not IL-8. 4. Carrageenin and LPS stimulated and production of immunoreactive
      TNFalpha, IL-1beta and IL-1ra in the skin of injected paws. 5. The inhibition by
      IL-1ra of the hyperalgesic response to carrageenin was not affected by antibodies
      neutralizing IL-4 and IL-10. 6. In mice, IL-1ra inhibited the nociceptive
      response to i.p. injection of acetic acid. 7. These data suggest that IL-1ra,
      released at sites of inflammation, limits inflammatory hyperalgesia. This effect
      is independent of (IL-1ra-induced) IL-4 and IL-10 and appears to be the result of
      antagonism by IL-1ra of IL-1beta-stimulated eicosanoid production.

PMID- 10903986
TI  - Selective agonist of group II glutamate metabotropic receptors, LY354740,
      inhibits tolerance to analgesic effects of morphine in mice.
AB  - 1. Antagonists of glutamate N-methyl-D-aspartate (NMDA) subtype receptor inhibit
      the development of tolerance to the antinociceptive effects of opioids. Another
      way to inhibit the function of glutamate receptors is the stimulation of
      presynaptic metabotropic group II (mGluRII) receptors. Because LY354740 ((+)-2
      aminobicyclo [3,1,0] hexane-2,6-dicarboxylic acid) is the first systemically
      active agonist of group II mGlu receptors, we investigated if this compound might
      inhibit the development of tolerance to antinociceptive effects of morphine and
      fentanyl. 2. As assessed by cumulative dose-response approach in the tail-flick
      test, administration of 10 mg kg(-1) morphine bid s.c. to male Albino Swiss mice
      for 6 days, right-shifted morphine dose-response curve by approximately 4 fold.
      In a separate group of mice, 12 injections of 0.04 mg kg(-1) of fentanyl over 3
      days, right-shifted fentanyl dose-response curve by approximately 3.3 fold. 3. In
      experiment 1, LY354740 (1 and 10, but not 0.1 mg kg(-1)) as well as the reference
      compound, an uncompetitive NMDA receptor antagonist memantine (7.5 mg kg(-1))
      inhibited the development of morphine tolerance. Neither LY354740 (10 mg kg(-1))
      nor memantine (7.5 mg kg(-1)) affected the development of tolerance to fentanyl.
      In experiment 2, neither LY354740 (1 and 10 mg kg(-1)) nor memantine (7.5 mg kg(
      1)) affected the tail-flick antinociceptive response, or the acute
      antinociceptive effect of morphine. 4. The present results are the first to
      suggest that the development of antinociceptive morphine tolerance may be
      inhibited by metabotropic group II glutamate agonist.

PMID- 10903988
TI  - Knockout blow for channel identity crisis : vasodilation to potassium is mediated
      via Kir2.1.

PMID- 10903990
TI  - Sustained inward current during pacemaker depolarization in mammalian sinoatrial
      node cells.
AB  - Several time- and voltage-dependent ionic currents have been identified in
      cardiac pacemaker cells, including Na(+) current, L- and T-type Ca(2+) currents,
      hyperpolarization-activated cation current, and various types of delayed
      rectifier K(+) currents. Mathematical models have demonstrated that spontaneous
      action potentials can be reconstructed by incorporating these currents, but
      relative contributions of individual currents vary widely between different
      models. In 1995, the presence of a novel inward current that was activated by
      depolarization to the potential range of the slow diastolic depolarization in
      rabbit sinoatrial (SA) node cells was reported. Because the current showed little
      inactivation during depolarizing pulses, it was called the sustained inward
      current (I(st)). A similar current is also found in SA node cells of the guinea
      pig and rat and in subsidiary pacemaker atrioventricular node cells. Recently,
      single-channel analysis has revealed a nicardipine-sensitive, 13-pS Na(+)
      current, which is activated by depolarization to the diastolic potential range in
      guinea pig SA node cells. This channel differs from rapid voltage-gated Na(+) or
      L-type Ca(2+) channels both in unitary conductance and gating kinetics. Because
      I(st) was observed only in spontaneously beating SA node cells, ie, it was absent
      in quiescent cells dissociated from the same SA or atrioventricular node, an
      important role of I(st) for generation of intrinsic cardiac automaticity was
      suggested.

PMID- 10903989
TI  - Nitric oxide and short-term hibernation: friend or foe?

PMID- 10903992
TI  - LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human
      endothelial cells: involvement of S-adenosylmethionine-dependent
      methyltransferases.
AB  - Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide synthase
      inhibitor. It is formed by protein arginine N-methyltransferases (PRMTs), which
      utilize S-adenosylmethionine as methyl group donor. ADMA plasma concentration is
      elevated in hypercholesterolemia, leading to endothelial dysfunction and
      producing proatherogenic changes of endothelial cell function. Four different
      isoforms of human PRMTs have been identified. Because the release of ADMA from
      human endothelial cells is increased in the presence of native or oxidized LDL
      cholesterol, we investigated the potential involvement of PRMT activity and gene
      expression in this effect. We found that the production of ADMA by human
      endothelial cells is upregulated in the presence of methionine or homocysteine
      and inhibited by either of the methyltransferase inhibitors S
      adenosylhomocysteine, adenosine dialdehyde, or cycloleucine. This effect is
      specific for ADMA but not symmetrical dimethylarginine. The upregulation of ADMA
      release by native and oxidized LDL is abolished by S-adenosylhomocysteine and by
      the antioxidant pyrrollidine dithiocarbamate. Furthermore, a methyl-(14)C label
      is transferred from S-adenosylmethionine to ADMA but not symmetrical
      dimethylarginine, in human endothelial cells. The expression of PRMTs is
      upregulated in the presence of native or oxidized LDL. Our data suggest that the
      production of ADMA by human endothelial cells is regulated by S
      adenosylmethionine-dependent methyltransferases. This activity is upregulated by
      LDL cholesterol, which may be due in part to the enhanced gene expression of
      PRMTs. In concentrations reached by stimulation of methyltransferases (5 to 50
      micromol/L), ADMA significantly inhibited the formation of (15)N-nitrite from L
      [guanidino-(15)N(2)]arginine. These findings suggest a novel mechanism by which
      ADMA concentration is elevated in hypercholesterolemia, leading to endothelial
      dysfunction and atherosclerosis.

PMID- 10903991
TI  - Heparin blockade of thrombin-induced smooth muscle cell migration involves
      inhibition of epidermal growth factor (EGF) receptor transactivation by heparin
      binding EGF-like growth factor.
AB  - Agonists of G protein-coupled receptors, such as thrombin, act in part by
      transactivating the epidermal growth factor (EGF) receptor (EGFR). Although at
      first a ligand-independent mechanism for EGFR transactivation was postulated, it
      has recently been shown that this transactivation by various G protein-coupled
      receptor agonists can involve heparin-binding EGF-like growth factor (HB-EGF).
      Because thrombin stimulation of vascular smooth muscle cell migration is blocked
      by heparin and because heparin can displace HB-EGF, we investigated the
      possibility that thrombin stimulation of smooth muscle cells (SMCs) depends on
      EGFR activation by HB-EGF. In rat SMCs, EGFR phosphorylation and extracellular
      signal-regulated kinase (ERK) activation in response to thrombin are inhibited
      not only by the EGFR inhibitor AG1478 and by EGFR blocking antibody but also by
      heparin and by neutralizing HB-EGF antibody. HB-EGF-dependent signaling induced
      by thrombin is inhibited by batimastat, which suggests a requirement for pro-HB
      EGF shedding by a metalloproteinase. We further demonstrate that this novel
      pathway is required for the migration of rat and baboon SMCs in response to
      thrombin. We conclude from these data that the inhibitory effect of heparin on
      SMC migration induced by thrombin relies, at least in part, on a blockade of HB
      EGF-mediated EGFR transactivation.

PMID- 10903993
TI  - Transmission of information from cardiac dihydropyridine receptor to ryanodine
      receptor: evidence from BayK 8644 effects on resting Ca(2+) sparks.
AB  - Coupling between L-type Ca(2+) channels (dihydropyridine receptors, DHPRs) and
      ryanodine receptors (RyRs) plays a pivotal role in excitation-contraction (E-C)
      coupling in cardiac myocytes, and Ca(2+) influx is generally accepted as the
      trigger of sarcoplasmic reticulum (SR) Ca(2+) release. The L-type Ca(2+) channel
      agonist BayK 8644 (BayK) has also been reported to alter RyR gating via a
      functional linkage between DHPR and RyR, independent of Ca(2+) influx. Here, the
      effect of rapid BayK application on resting RyR gating in intact ferret
      ventricular myocytes was measured as Ca(2+) spark frequency (CaSpF) by confocal
      microscopy and fluo 3. BayK increased resting CaSpF by 401+/-15% within 10
      seconds in Ca(2+)-free solution, and depolarization had no additional effect. The
      effect of BayK on CaSpF was dose-dependent, but even 50 nmol/L BayK induced a
      rapid 245+/-12% increase in CaSpF. Nifedipine (5 micromol/L) had no effect by
      itself on CaSpF, but it abolished the BayK effect (presumably by competitive
      inhibition at the DHPR). The nondihydropyridine Ca(2+) channel agonist FPL-64176
      (1 micromol/L) did not alter CaSpF (despite rapid and potent enhancement of
      Ca(2+) current, I(Ca)). In striking contrast to the very rapid and depolarization
      independent effect of BayK on CaSpF, BayK increased I(Ca) only slowly (tau=18
      seconds), and the effect was greatly accelerated by depolarization. We conclude
      that in ferret ventricular myocytes, BayK effects on I(Ca) and CaSpF both require
      drug binding to the DHPR, but postreceptor pathways may diverge in transmission
      to the gating of the L-type Ca(2+) channel and RyR.

PMID- 10903994
TI  - Inhibition by protein kinase C of the K(NDP) subtype of vascular smooth muscle
      ATP-sensitive potassium channel.
AB  - ATP-sensitive K(+) channels (K(ATP)) contribute to the regulation of tone in
      vascular smooth muscle cells. We determined the effects of protein kinase C (PKC)
      activation on the nucleoside diphosphate-activated (K(NDP)) subtype of vascular
      smooth muscle K(ATP) channel. Phorbol 12,13-dibutyrate (PdBu) and angiotensin II
      inhibited K(NDP) activity of C-A patches of rabbit portal vein (PV) myocytes, but
      an inactive phorbol ester was without effect, and pretreatment with PKC inhibitor
      prevented the actions of PdBu. Constitutively active PKC inhibited K(NDP) in I-O
      patches but was without effect in the presence of a specific peptide inhibitor of
      PKC. PdBu increased the duration of a long-lived interburst closed state but was
      without effect on burst duration or intraburst kinetics. PdBu treatment inhibited
      K(NDP), but not a 70-pS K(ATP) channel of rat PV. The results indicate that the
      K(NDP) subtype of vascular smooth muscle K(ATP) channel is inhibited by
      activation of PKC. Control of K(NDP) activity by intracellular signaling cascades
      involving PKC may, therefore, contribute to control of tone and arterial diameter
      by vasoconstrictors.

PMID- 10903995
TI  - Morphological and molecular characterization of adult cardiomyocyte apoptosis
      during hypoxia and reoxygenation.
AB  - Apoptosis has been implicated in ischemic heart disease, but its mechanism in
      cardiomyocytes has not been elucidated. In this study, we investigate the effects
      of hypoxia and reoxygenation in adult cardiomyocytes and the molecular mechanism
      involved in cardiomyocyte apoptosis. Morphologically, reoxygenation induced
      rounding up of the cells, appearance of membrane blebs that were filled with
      marginated mitochondria, and ultrastructural findings characteristic of
      apoptosis. Reoxygenation (18 hours of reoxygenation after 6 hours of hypoxia) and
      prolonged hypoxia (24 hours of hypoxia) resulted in a 59% and 51% decrease in
      cellular viability, respectively. During reoxygenation, cell death occurred
      predominantly via apoptosis associated with appearance of cytosolic cytochrome c
      and activation of caspase-3 and -9. However, nonapoptotic cell death predominated
      during prolonged hypoxia. Both caspase inhibition and Bcl-2 overexpression during
      reoxygenation significantly improved cellular viability through inhibition of
      apoptosis but had minimal effect on hypoxia-induced cell death. Bcl-2
      overexpression blocked reoxygenation-induced cytochrome c release and activation
      of caspase -3 and -9, but caspase inhibition alone did not block cytochrome c
      release. These results suggest that apoptosis predominates in cardiomyocytes
      after reoxygenation through a mitochondrion-dependent apoptotic pathway, and Bcl
      2 prevents reoxygenation-induced apoptosis by inhibiting cytochrome c release
      from the mitochondria and prevents activation of caspase-3 and -9.

PMID- 10903996
TI  - Release of active tissue factor by human arterial smooth muscle cells.
AB  - Tissue factor (TF), the initiator of coagulation, is thought to function
      predominantly at the cell surface. Recent data have suggested that active TF is
      present extracellularly in atherosclerotic plaques, the arterial wall, and the
      blood. This study was conducted to determine whether smooth muscle cells (SMCs),
      a major source of arterial TF, could generate extracellular TF. Active TF
      accumulated in the medium of cultured human SMCs, representing approximately 10%
      of that measured in the underlying cells at 24 hours. Platelet-derived growth
      factor, phorbol ester, and tumor necrosis factor-alpha caused approximately 3
      fold increases in TF activity in the medium. Release of TF into the medium was
      dependent on the presence of the TF transmembrane domain but not the cytoplasmic
      domain. Antibodies to TF precipitated most of the activity from the culture
      medium, whereas antibodies to the beta(1)-integrin subunit precipitated
      approximately 33% of the activity. Treatment with detergent or
      phosphatidylserine:phosphatidylcholine did not increase activity, suggesting that
      all TF released by SMCs was in the appropriate lipid milieu and not encrypted.
      Western blotting showed that the medium contained full-length TF protein.
      Fluorescent cytometry showed that extracellular TF was present largely in
      particles < or =200 nm, which had a density of 1.10 g/mL. We hypothesize that
      active extracellular TF found in the injured arterial wall and atherosclerotic
      plaques derives, in part, from SMC microparticles.

PMID- 10903997
TI  - Plasminogen is a critical determinant of vascular remodeling in mice.
AB  - Extracellular proteolysis is likely to be a feature of vascular remodeling
      associated with atherosclerotic and restenotic arteries. To investigate the role
      of plasminogen-mediated proteolysis in remodeling, polyethylene cuffs were placed
      around the femoral arteries of mice with single and combined deficiencies in
      plasminogen and fibrinogen. Neointimal development occurred in all mice and was
      unaffected by genotype. Significant compensatory medial remodeling occurred in
      the cuffed arteries of control mice but not in plasminogen-deficient mice.
      Furthermore, focal areas of medial atrophy were frequently observed in
      plasminogen-deficient mice but not in control animals. A simultaneous deficit of
      fibrinogen restored the potential of the arteries of plasminogen-deficient mice
      to enlarge in association with neointimal development but did not eliminate the
      focal medial atrophy. An intense inflammatory infiltrate occurred in the
      adventitia of cuffed arteries, which was associated with enhanced matrix
      deposition. Adventitial collagen deposition was apparent after 28 days in control
      and fibrinogen-deficient arteries but not in plasminogen-deficient arteries,
      which contained persistent fibrin. These studies demonstrate that plasmin(ogen)
      contributes to favorable arterial remodeling and adventitial collagen deposition
      via a mechanism that is related to fibrinogen, presumably fibrinolysis. In
      addition, these studies reveal a fibrin-independent role of plasminogen in
      preventing medial atrophy in challenged vessels.

PMID- 10903998
TI  - Nitric oxide inhalation decreases pulmonary artery remodeling in the injured
      lungs of rat pups.
AB  - Vascular injury causes the muscularization of peripheral pulmonary arteries,
      which is more pronounced in the infant than in the adult lung. Although inhaled
      NO gas attenuates pulmonary artery remodeling in hypoxic rats, whether or not it
      protects the lung by mitigating vasoconstriction is unknown. This investigation
      tested whether inhaled NO decreases the muscularization of injured pulmonary
      arteries in rat pups by modulating vascular tone. One week after monocrotaline
      administration, the percentage of muscularized rat pup lung arteries was
      increased by >3-fold. Nevertheless, monocrotaline exposure did not cause right
      ventricular hypertrophy, pulmonary hypertension, or vasoconstriction. In
      addition, it did not increase the expression of markers of inflammation
      (interleukin-1beta, intercellular adhesion molecule-1, and E-selectin) or of
      platelet-mediated thrombosis (GPIbalpha). Continuous inhalation of 20 ppm NO gas
      prevented the neomuscularization of the pulmonary arteries in pups with lung
      injury. Moreover, a 3-fold increase in cell proliferation and 30% decrease in
      cell numbers in pulmonary arteries caused by monocrotaline exposure was prevented
      by NO inhalation. These data indicate that inhaled NO protects infants against
      pulmonary remodeling induced by lung injury by mechanisms that are independent of
      pulmonary tone, inflammation, or thrombosis.

PMID- 10903999
TI  - Endogenous nitric oxide and myocardial adaptation to ischemia.
AB  - Ischemic myocardium does not inevitably undergo necrosis but rather can survive
      through downregulation of contractile function, ie, "hibernate." To study the
      role of endogenous NO in this adaptation, 41 enflurane-anesthetized swine were
      subjected to 90 minutes of moderate left anterior descending coronary artery
      hypoperfusion and assigned to placebo (P), to 30 mg/kg N(G)-nitro-L-arginine (L
      NNA) IV to inhibit NO synthase, or to aortic constriction (AO) to match the
      increased left ventricular pressure observed with L-NNA. During normoperfusion, a
      regional myocardial external work index (WI, mm Hg. mm, sonomicrometry and
      micromanometry) was reduced with L-NNA (from 326+/-27 [SEM] to 250+/-19, P<0.05)
      but increased with AO (from 321+/-16 to 363+/-19, P<0.05 versus L-NNA). At 10
      minutes of ischemia, WI was lower with L-NNA (109+/-10, P<0.05) than P (180+/-22)
      and AO (170+/-11) and did not change further at 85 minutes of ischemia.
      Relationships between WI and transmural myocardial blood flow and oxygen
      consumption were shifted rightward by L-NNA versus P and AO at both 10 and 85
      minutes of ischemia. The maximal increment in calcium-activated external work was
      not different during normoperfusion among groups but was decreased during
      ischemia with L-NNA. L-NNA transiently increased myocardial contractile calcium
      sensitivity along with systemic pressure but reduced it during ongoing ischemia.
      The free-energy change of ATP hydrolysis after an early ischemic decrease
      recovered toward baseline values in all groups, and necrosis was absent after 2
      (triphenyltetrazolium chloride staining) or 8 (histology) hours of reperfusion.
      Thus, endogenous NO contributes to hibernation by reducing oxygen consumption and
      preserving calcium sensitivity and contractile function without an energy cost
      during ischemia.

PMID- 10904002
TI  - Addendum

PMID- 10904000
TI  - Role of vascular cell adhesion molecule-1 and fibronectin connecting segment-1 in
      monocyte rolling and adhesion on early atherosclerotic lesions.
AB  - Atherosclerotic lesion development seems to be inflammatory in nature and
      involves the recruitment of monocytes to the vessel wall. In this study, we
      investigated the role of vascular cell adhesion molecule-1 (VCAM-1) and
      fibronectin (FN) connecting segment-1 containing the amino acid sequence ILDV as
      functional ligands for alpha(4)beta(1) integrin (VLA-4) in monocyte rolling and
      adherence to early atherosclerotic lesions. Carotid arteries of apolipoprotein E
      deficient mice were isolated and perfused with monocytes or U937 cells. Cell
      adhesion was reduced 95+/-4% by monoclonal antibodies HP1/2 and HP2/1, which
      block VLA-4 binding to both VCAM-1 and FN connecting segment-1. mAb HP1/3
      preferentially blocked interaction of VLA-4 with FN but not VCAM-1 and decreased
      adhesion by 30+/-8%. In contrast, blocking VCAM-1 by perfusing the isolated
      carotid artery with mAb MK-2.7 reduced adhesion by 75+/-12%. Mononuclear cell
      adhesion to the early atherosclerotic endothelium was inhibited by 68+/-10% in
      the presence of EILDVPST but not in the presence of control peptide EIDVLPST.
      When VLA-4 or VCAM-1 was blocked, more mononuclear cells rolled on early lesions
      at significantly higher (approximately doubled) rolling velocities. These data
      demonstrate that (1) blockade of VCAM-1 can abrogate the majority (75+/-12%) of
      VLA-4-dependent monocyte adhesion on early atherosclerotic endothelia and (2)
      ILDV peptide interferes with VLA-4 binding to both VCAM-1 and FN and may be
      useful in limiting monocyte adhesion to atherosclerotic lesions.

PMID- 10904003
TI  - Janice M. Pfeffer, PhD

PMID- 10904001
TI  - Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the
      inwardly rectifying K(+) current in K(+)-mediated vasodilation.
AB  - The molecular bases of inwardly rectifying K(+) (Kir) currents and K(+)-induced
      dilations were examined in cerebral arteries of mice that lack the Kir2.1 and
      Kir2.2 genes. The complete absence of the open reading frame in animals
      homozygous for the targeted allele was confirmed. Kir2.1(-/-) animals die 8 to 12
      hours after birth, apparently due to a complete cleft of the secondary palate. In
      contrast, Kir2.2(-/-) animals are viable and fertile. Kir currents were observed
      in cerebral artery myocytes isolated from control neonatal animals but were
      absent in myocytes from Kir2.1(-/-) animals. Voltage-dependent K(+) currents were
      similar in cells from neonatal control and Kir2.1(-/-) animals. An increase in
      the extracellular K(+) concentration from 6 to 15 mmol/L caused Ba(2+)-sensitive
      dilations in pressurized cerebral arteries from control and Kir2.2 mice. In
      contrast, arteries from Kir2.1(-/-) animals did not dilate when the extracellular
      K(+) concentration was increased to 15 mmol/L. In summary, Kir2.1 gene expression
      in arterial smooth muscle is required for Kir currents and K(+)-induced dilations
      in cerebral arteries.

PMID- 10904004
TI  - Combinations of variations in multiple genes are associated with hypertension.
AB  - The genetic analysis of hypertension has revealed complex and inconsistent
      results, making it difficult to draw clear conclusions regarding the impact of
      specific genes on blood pressure regulation in diverse human populations. Some of
      the confusion from previous studies is probably due to undetected gene-gene
      interactions. Instead of focusing on the effects of single genes on hypertension,
      we examined the effects of interactions of alleles at 4 candidate loci. Three of
      the loci are in the renin-angiotensin-system, angiotensinogen, ACE, and
      angiotensin II type 1 receptor, and they have been associated with hypertension
      in at least 1 previous study. The fourth locus studied is a previously
      undescribed locus, named FJ. In total, 7 polymorphic sites at these loci were
      analyzed for their association with hypertension in 51 normotensive and 126
      hypertensive age-matched individuals. There were no significant differences
      between the 2 phenotypic classes with respect to either allele or genotype
      frequencies. However, when we tested for nonallelic associations (linkage
      disequilibrium), we found that of the 120 multilocus comparisons, 16 deviated
      significantly from random in the hypertensive class, but there were no
      significant deviations in the normotensive group. These findings suggest that
      genetic interactions between multiple loci rather than variants of a single gene
      underlie the genetic basis of hypertension in our study subjects. We hypothesize
      that such interactions may account for the inconsistent findings in previous
      studies because, unlike our study, prior studies almost always examined single
      locus effects and did not consider the effects of variation at other potentially
      interacting loci.

PMID- 10904005
TI  - Genetic determinants of hypertension: identification of candidate phenotypes.
AB  - Our long-term objective is to identify genes whose expression results in
      hypertension and in phenotypic changes that may contribute to hypertension. The
      purpose of the present study was to describe evidence for the heritability of
      hypertension-related phenotypes in hypertensive, hyperlipidemic black sib pairs.
      Outpatient anthropomorphic measurements were obtained in >200 affected sib pairs.
      In addition, 68 of these sib pairs were studied under controlled, standardized
      conditions at an inpatient clinical research center while off both
      antihypertensive and lipid-lowering medications. Heritability was estimated on
      the basis of sib-sib correlations and with an association model. Higher
      heritability estimates for blood pressure were observed with multiple
      measurements averaged over 24 hours than with measurements at a single time
      point, and heritability estimates for nighttime blood pressures were higher than
      those for daytime blood pressures. Heritability estimates for several of the
      phenotypes were augmented by obtaining measurements in response to a standardized
      stimulus, including (1) blood pressure responses to the assumption of upright
      posture, standardized psychological stress, and norepinephrine infusion; (2)
      plasma renin, aldosterone, epinephrine, and cAMP and cGMP responses to the
      assumption of upright posture; (3) para-aminohippurate and inulin clearances in
      response to norepinephrine infusion; and (4) plasma arginine vasopressin in
      response to NaCl infusion. High heritability estimates were also observed for
      various measures of body size and body fat, left ventricular size, cardiac index,
      stroke volume, total peripheral resistance, and serum concentrations of LDL and
      HDL cholesterol and leptin. These heritability estimates identify the
      hypertension-related phenotypes that may facilitate the identification of
      specific genetic determinants of hypertension in blacks with hyperlipidemia.

PMID- 10904006
TI  - Role of tumor necrosis factor-alpha gene locus in obesity and obesity-associated
      hypertension in French Canadians.
AB  - Obesity represents a serious risk factor for the development of cardiovascular
      diseases, including hypertension. Segregation studies suggest that obesity and
      obesity-associated hypertension may share some genetic determinants. The results
      of the present candidate gene investigation suggest that in hypertensive
      pedigrees of French-Canadian origin, one such determinant is the tumor necrosis
      factor (TNF)-alpha gene locus. Gender-pooled quantitative sib-pair analysis
      demonstrated a significant effect of the gene locus on 3 global and 7 regional
      measures of obesity (P=0.05 to 0.0004). Gender-separate quantitative sib-pair
      analyses showed that the impact of the locus on obesity is most significant in
      the abdominal region in men and in the thigh region in women. Furthermore, the
      haplotype relative-risk test demonstrated a significant association between the
      TNF-alpha gene locus and both obesity (P=0.006) and obesity-associated
      hypertension (P=0.02). These effects were most significant in individuals with
      nonmorbid obesity. In conclusion, the results of linkage and association analyses
      suggest that in hypertensive pedigrees of French-Canadian origin, the TNF-alpha
      gene locus contributes to the determination of obesity and obesity-associated
      hypertension. In addition, the data indicate that gender modifies the effect of
      the locus on the regional distribution of body fat.

PMID- 10904007
TI  - Differentiated long-term effects of intentional weight loss on diabetes and
      hypertension.
AB  - The beneficial effects of weight loss in the obese have been widely accepted.
      Still, there is a lack of controlled studies displaying large maintained weight
      losses over long periods (>4 years). We wanted to examine the results of long
      standing intentional weight loss on the development of diabetes and hypertension
      in severely obese individuals over an 8-year period. In the ongoing prospective
      Swedish Obese Subjects (SOS) study, 346 patients awaiting gastric surgery were
      matched with 346 obese control subjects on 18 variables by a computerized
      matching program. The controls were drawn from a registry consisting of 1508
      obese potential controls examined at primary health care centers in Sweden. Of
      the 692 selected patients (body mass index 41.2+/-4.7 kg/m(2) [mean+/-SD]), 483
      (70%) were followed for 8 years. No significant weight changes occurred in the
      obese control group over 8 years. Gastric surgery resulted in a maximum weight
      loss of -31.1+/-13.6 kg after 1 year. After 8 years, the maintained weight loss
      was still 20.1+/-15.7 kg (16.3+/-12.3%). Whereas this weight reduction had a
      dramatic effect on the 8-year incidence of diabetes (odds ratio 0.16, 95% CI 0.07
      to 0.36), it had no effect on the 8-year incidence of hypertension (odds ratio
      1.01, 95% CI 0.61 to 1.67). A differentiated risk factor response was identified:
      a maintained weight reduction of 16% strongly counteracted the development of
      diabetes over 8 years but showed no long-term effect on the incidence of
      hypertension.

PMID- 10904008
TI  - Resting metabolic rate and substrate use in obesity hypertension.
AB  - There is substantial evidence that obesity is a prime risk factor for the
      development of hypertension. Although hyperinsulinemia and an increased activity
      of the sympathetic nervous system have been implicated in the pathogenesis of
      "obesity hypertension," their effects on energy metabolism have not been studied
      thus far. In the present study, we therefore examined resting metabolic rate
      (RMR) and basal substrate oxidation in subjects with obesity and obesity-related
      hypertension. A total of 166 subjects were characterized for RMR and basal
      substrate use through indirect calorimetry. Blood pressure was measured at rest
      and with 24-hour ambulatory monitoring. Blood samples were collected for the
      measurement of plasma catecholamines, leptin, and the insulin response to an oral
      glucose load. In our study population, 116 subjects were defined as hypertensive
      and 91 were defined as obese. Hypertensive patients under beta-adrenergic
      blockade (n=42) had a significantly lower RMR than did patients without beta
      blockade (P<0. 05) and were therefore excluded from further analyses. Univariate
      regression analysis revealed a significant relationship between RMR and body fat
      mass, as well as body fat-free mass, in both groups. Compared with obese
      normotensive control subjects (n=27), obese hypertensives (n=43) had a 9% higher
      RMR (P<0.05), higher plasma catecholamine (P<0.05) and leptin (P<0.05) levels,
      and an increased insulin response to oral glucose (P<0.01). Together, these
      findings are compatible with the idea that chronic neurogenic and metabolic
      adaptations related to obesity may play a role in the development of obesity
      hypertension in susceptible individuals.

PMID- 10904009
TI  - G protein beta 3 gene: structure, promoter, and additional polymorphisms.
AB  - Recent studies have shown that a polymorphism (C825T) in the gene encoding the G
      protein beta 3 subunit (GNB3) is associated with hypertension and obesity. We
      characterized the entire GNB3 gene, which spans 7.5 kb and is composed of 11
      exons and 10 introns. Its promoter lacks a TATA box but harbors GC-rich regions.
      The functional activity of the GNB3 promoter was verified with reporter gene
      assays that also demonstrated its inducibility by phorbol esters. A novel
      polymorphism in the promoter region A(-350)G occurred with frequencies (G allele)
      of 76%, 97%, and 61% in Africans, Chinese, and Germans, respectively. Reporter
      gene constructs with either the A or the G allele did not differ with regard to
      inducement of the reporter protein. A silent nucleotide exchange in the coding
      region (A657T) occurred with T allele frequencies ranging from 0.5% to 2.4%.
      Another polymorphism (G814A) results in the replacement of glycine by serine at
      position 272. In Germans, the A allele occurred at a frequency of 10%. Finally, a
      C1429T polymorphism in the 3' untranslated region of GNB3 was identified that
      occurred at T allele frequencies of 38%, 17%, and 30% in Africans, Chinese, and
      Germans, respectively. Haplotype prediction indicated in Germans an almost
      complete association of GNB3 825T with 1429T, and vice versa. An analysis of
      these polymorphic loci in nonhuman primates revealed that the ancestral GNB3 gene
      harbored the (-350)G, 825C, and 1429C alleles. This is the first complete
      characterization of the human GNB3 gene and its promoter region, which will
      enable refined epidemiological and biochemical investigations of GNB3 in
      hypertension and obesity.

PMID- 10904010
TI  - Increase in G(i alpha) protein accompanies progression of post-infarction
      remodeling in hypertensive cardiomyopathy.
AB  - Hypertensive cardiac hypertrophy and myocardial infarction (MI) are clinically
      relevant risk factors for heart failure. There is no specific information
      addressing signaling alterations in the sequence of hypertrophy and post-MI
      remodeling. To investigate alterations in beta-adrenergic receptor G-protein
      signaling in ventricular remodeling with pre-existing hypertrophy, MI was induced
      by coronary artery ligation in Wistar-Kyoto rats (WKY) and spontaneously
      hypertensive rats (SHR). Ten weeks after the induction of MI, the progression of
      left ventricular dysfunction and increases in plasma atrial natriuretic peptide
      (ANP) and cardiac ANP mRNA were more pronounced in SHR than WKY. In addition, the
      impaired contractile response to beta-adrenergic stimulation was observed in the
      noninfarcted papillary muscle isolated from SHR. Immunochemical G(s alpha)
      protein and beta-adrenoceptor density were not significantly altered by MI in
      both strains. However, immunochemical G(i alpha) was increased (1.5-fold) in the
      noninfarcted left ventricle of the SHR in which infarction had been induced when
      compared with that in SHR that underwent sham operation. This increase was
      observed especially in rats with a high plasma ANP level. Furthermore, there was
      a positive correlation between G(i alpha) and the extent of post-MI remodeling in
      WKY. A similar correlation between G(i alpha) and the extent of hypertensive
      hypertrophy was observed in SHR. In conclusion, the vulnerability of
      hypertrophied hearts to ischemic damage is greater than that of normotensive
      hearts. An increase in G(i alpha) could be one mechanism involved in the
      transition from cardiac hypertrophy to cardiac failure when chronic pressure
      overload and loss of contractile mass from ischemic heart disease coexist.

PMID- 10904011
TI  - Cardiac ankyrin repeat protein is a novel marker of cardiac hypertrophy: role of
      M-CAT element within the promoter.
AB  - CARP, a cardiac doxorubicin (adriamycin)-responsive protein, has been identified
      as a nuclear protein whose expression is downregulated in response to
      doxorubicin. In the present study, we tested the hypothesis that CARP serves as a
      reliable genetic marker of cardiac hypertrophy in vivo and in vitro. CARP
      expression was markedly increased in 3 distinct models of cardiac hypertrophy in
      rats: constriction of abdominal aorta, spontaneously hypertensive rats, and Dahl
      salt-sensitive rats. In addition, we found that CARP mRNA levels correlate very
      strongly with the brain natriuretic peptide mRNA levels in Dahl rats. Transient
      transfection assays into primary cultures of neonatal rat cardiac myocytes
      indicate that transcription from the CARP and brain natriuretic peptide promoters
      is stimulated by overexpression of p38 and Rac1, components of the stress
      activated mitogen-activated protein kinase pathways. Mutation analysis and
      electrophoretic mobility shift assays indicated that the M-CAT element can serve
      as a binding site for nuclear factors, and this element is important for the
      induction of CARP promoter activity by p38 and Rac1. Thus, our data suggest that
      M-CAT element is responsible for the regulation of the CARP gene in response to
      the activation of stress-responsive mitogen-activated protein kinase pathways.
      Moreover, given that activation of these pathways is associated with cardiac
      hypertrophy, we propose that CARP represents a novel genetic marker of cardiac
      hypertrophy.

PMID- 10904012
TI  - Performance of classic electrocardiographic criteria for left ventricular
      hypertrophy in an African population.
AB  - ECG criteria for left ventricular hypertrophy (LVH) have been almost exclusively
      elaborated and calibrated in white populations. Because several interethnic
      differences in ECG characteristics have been found, the applicability of these
      criteria to African individuals remains to be demonstrated. We therefore
      investigated the performance of classic ECG criteria for LVH detection in an
      African population. Digitized 12-lead ECG tracings were obtained from 334 African
      individuals randomly selected from the general population of the Republic of
      Seychelles (Indian Ocean). Left ventricular mass was calculated with M-mode
      echocardiography and indexed to body height. LVH was defined by taking the 95th
      percentile of body height-indexed LVM values in a reference subgroup. In the
      entire study sample, 16 men and 15 women (prevalence 9.3%) were finally declared
      to have LVH, of whom 9 were of the reference subgroup. Sensitivity, specificity,
      accuracy, and positive and negative predictive values for LVH were calculated for
      9 classic ECG criteria, and receiver operating characteristic curves were
      computed. We also generated a new composite time-voltage criterion with stepwise
      multiple linear regression: weighted time-voltage
      criterion=(0.2366R(aVL)+0.0551R(V5)+0.0785S(V3)+ 0.2993T(V1))xQRS duration. The
      Sokolow-Lyon criterion reached the highest sensitivity (61%) and the R(aVL)
      voltage criterion reached the highest specificity (97%) when evaluated at their
      traditional partition value. However, at a fixed specificity of 95%, the
      sensitivity of these 10 criteria ranged from 16% to 32%. Best accuracy was
      obtained with the R(aVL) voltage criterion and the new composite time-voltage
      criterion (89% for both). Positive and negative predictive values varied
      considerably depending on the concomitant presence of 3 clinical risk factors for
      LVH (hypertension, age >/=50 years, overweight). Median positive and negative
      predictive values of the 10 ECG criteria were 15% and 95%, respectively, for
      subjects with none or 1 of these risk factors compared with 63% and 76% for
      subjects with all of them. In conclusion, the performance of classic ECG criteria
      for LVH detection was largely disparate and appeared to be lower in this
      population of East African origin than in white subjects. A newly generated
      composite time-voltage criterion might provide improved performance. The
      predictive value of ECG criteria for LVH was considerably enhanced with the
      integration of information on concomitant clinical risk factors for LVH.

PMID- 10904014
TI  - Renal structural properties in prehypertensive Dahl salt-sensitive rats.
AB  - In 10- to 12-week-old Dahl salt-sensitive (DS) and salt-resistant (DR) rats fed a
      0.3% salt diet (n=10 in each group), flow-pressure and pressure-glomerular
      filtration rate (F-P and P-GFR, respectively) relationships were established for
      maximally vasodilated perfused kidneys. From these relationships, 3 indices of
      vascular structural properties were estimated: slope of F-P (minimal renal
      vascular resistance reflecting overall luminal dimensions of preglomerular and
      postglomerular vasculature), slope of P-GFR (glomerular filtration capability
      against pressure), and threshold pressure for beginning filtration at P-GFR
      (preglomerular-to-postglomerular vascular resistance ratio). Thereafter, maximal
      renal vascular resistance was determined to assess wall-to-lumen ratios of the
      resistance vessels in half of each group. In the remainder, the kidneys were
      perfusion-fixed for histological analysis. Mean arterial pressure did not differ
      between the DS and DR rats. There were no significant differences in the slopes
      of F-P between the 2 groups. In contrast, the slope of P-GFR was significantly
      lower (33%) in DS rats than in DR rats, although the DS kidneys began filtering
      at a threshold pressure similar to that of the DR kidneys. Thus, in DS rats,
      there were no abnormalities in luminal dimensions at preglomerular and
      postglomerular vascular segments, but the kidney filtration capacity decreased at
      any given increase in pressure. Maximal vascular resistance was greater in DS
      than in DR rats, a finding compatible with the histological appearance, which
      showed vascular hypertrophy with little, if any, vascular narrowing in the
      interlobular arteries of DS rats. In conclusion, hypertrophic remodeling without
      vascular narrowing at preglomerular resistance vessels and structural defects in
      filtering at the glomeruli could occur in prehypertensive DS rats.

PMID- 10904013
TI  - Hypertension in black patients: an emerging role of the endothelin system in salt
      sensitive hypertension.
AB  - The prevalence of essential hypertension in blacks is much higher than that in
      whites. In addition, the pathogenesis of hypertension appears to be different in
      black patients. For example, black patients present with a salt-sensitive
      hypertension characterized by low renin levels. Racial differences in renal
      physiology and socioeconomic factors have been suggested as possible causes of
      this difference, but reasons for this difference remain unclear. Endothelial
      cells are important in the regulation of vascular tonus and homeostasis, in part
      through the secretion of vasoactive substances. One of these factors, endothelin
      1 (ET-1), is a 21 amino acid residue peptide with potent vasopressor actions. In
      addition to its contractile effects, it has been shown to stimulate mitogenesis
      in a number of cell types. Moreover, ET-1 displays modulatory effects on the
      endocrine system, including stimulation of angiotensin II and aldosterone
      production and inhibition of antidiuretic hormone in the kidney. Recent data from
      several laboratories indicate that ET-1 is overexpressed in the vasculature in
      several salt-sensitive models of experimental hypertension. Moreover, circulating
      plasma ET-1 levels are significantly increased in black hypertensives compared
      with white hypertensives. Thus, the ET system might be particularly important in
      the development or maintenance of hypertension in this population.

PMID- 10904015
TI  - Prevalence and risk factors of silent cerebral infarction in apparently normal
      adults.
AB  - Cerebrovascular disease is a major cause of death and disability in adults.
      Silent cerebral infarction (SCI) portends more severe cerebral infarctions or may
      lead to insidious progressive brain damage resulting in vascular dementia. This
      study was designed to evaluate the prevalence and risk factors of SCI in an
      apparently normal adult population. Nine hundred ninety-four consecutive symptom
      free adults (mean age 49.0+/-7.7; men:women 830:164) who underwent brain magnetic
      resonance imaging at the Center for Health Promotion at Samsung Medical Center
      were assessed. All were neurologically normal in history and physical
      examination. A total of 121 SCI lesions was observed in 58 subjects. The lesion
      prevalence adjusted for patient age was 5.1%. There was no gender difference in
      prevalence. Ninety-nine lesions were <1 cm in diameter, 15 were between 1 and 2
      cm, 3 were between 2 and 3 cm, and 4 were >3 cm in diameter. The most frequent
      site of the SCI lesion was basal ganglia, after which the periventricular white
      matter, cerebral cortex, and thalamus were the most frequent sites. Old age,
      hypertension, a history of coronary artery disease, evidence of cardiomegaly in
      chest radiographs, and high fasting glucose/hemoglobin A1c levels were associated
      with SCI on univariate analysis. Multivariate analysis demonstrated old age and
      hypertension to be independent risk factors for SCI, and mild alcohol consumption
      was revealed as an independent protective factor against SCI.

PMID- 10904016
TI  - Vascular compression of the rostral ventrolateral medulla in sympathetic mediated
      essential hypertension.
AB  - The pathophysiological factors of neurogenic or sympathetically mediated
      essential hypertension are unknown. Neurons close to the surface of the
      ventrolateral medulla (specifically, in the retro-olivary sulcus [ROS]) are
      integrally involved in the control of blood pressure by means of efferent
      connections to presympathetic neurons in the spinal cord. It is hypothesized that
      vascular contact with the ROS is pathogenically involved in neurogenically
      mediated hypertension. We evaluated that theory in 20 subjects with uncomplicated
      stage 1 to stage 2 essential hypertension (EHTN) (18 of whom completed the
      study). The baseline supine plasma norepinephrine level served as an index of
      central sympathetic outflow. The response of blood pressure to clonidine was used
      as a surrogate marker for neurogenically mediated hypertension. We also examined
      the relationship between those markers and evidence of anatomic abnormalities in
      the area of the ROS that was provided by magnetic resonance imaging. A vessel
      contacted the left ROS in 5 of the 18 subjects. Those 5 subjects had higher
      plasma norepinephrine concentrations than did the 13 subjects without this
      vascular contact (358+/-46 versus 76+/-43 pg/mL, P<0.001). These 5 subjects also
      exhibited a significant depressor response to clonidine that tended to be greater
      than that seen in the 13 subjects without vascular contact (-20.6+/-3.2 versus 
      13.6+/-9 mm Hg). Both race and baseline mean blood pressure had only an
      independent effect on the depressor response to clonidine. The findings are
      consistent with the theory that vascular contact with the left ROS may contribute
      to neurogenically mediated "essential" hypertension in some patients.

PMID- 10904017
TI  - Adrenomedullin and nitric oxide inhibit human endothelial cell apoptosis via a
      cyclic GMP-independent mechanism.
AB  - Adrenomedullin, which was discovered as a vasodilating peptide, has been reported
      to be produced in various organs, in which adrenomedullin regulates not only
      vascular tone but also cell proliferation and differentiation in an
      autocrine/paracrine manner. We evaluated the effect of adrenomedullin on
      endothelial cell apoptosis. Human umbilical vein endothelial cells underwent
      apoptosis when cultured in serum-free medium. Treatment with adrenomedullin
      reduced the number of cells with pyknotic nuclei (Hoechst 33258 staining) and
      inhibited cell death (dimethylthiazol-diphenyltetrazolium bromide assay) in a
      dose-dependent manner. The administration of adrenomedullin did not alter the
      expression levels of Bcl-2 family proteins. Experiments with analogs of cAMP or a
      cAMP-elevating agonist demonstrated that elevation of the intracellular cAMP
      concentration does not mediate the antiapoptotic effect of adrenomedullin. The
      coadministration of N-nitro-L-arginine methyl ester (2 mmol/L), an inhibitor of
      nitric oxide synthase, abrogated the effect of adrenomedullin. Lower doses of
      sodium nitroprusside (1 to 10 micromol/L), a nitric oxide donor, mimicked the
      antiapoptotic effect of adrenomedullin. The antiapoptotic effect of sodium
      nitroprusside was not attenuated by the inhibition of soluble guanylyl cyclase
      with 1 micromol/L oxadiazolo-quinoxalin-1-one nor could apoptosis be inhibited by
      the incubation of human umbilical vein endothelial cells with 1 mmol/L 8-bromo
      cGMP, a cell-permeant cGMP analog. These results indicate that adrenomedullin and
      nitric oxide inhibit endothelial cell apoptosis via a cGMP-independent mechanism.

PMID- 10904018
TI  - Blood flow regulates the development of vascular hypertrophy, smooth muscle cell
      proliferation, and endothelial cell nitric oxide synthase in hypertension.
AB  - Blood flow participates in vascular remodeling during development and growth by
      regulating cell apoptosis and proliferation. However, its significance in the
      development of vascular hypertrophy and vascular remodeling in hypertensive
      patients is not known. We investigated how changing blood flow through the common
      carotid artery (CA) of young adult rats rendered hypertensive via aortic
      coarctation affects CA hypertrophy and/or remodeling responses to hypertension.
      Blood flow was reduced by approximately 50% as a result of ligation of the
      external CA immediately after hypertension was induced, and the effects of that
      procedure were compared with those in similarly treated normotensive rats.
      Reducing blood flow in the hypertensive animals markedly augmented the
      development of CA hypertrophy over the ensuing 14 days by increasing the vessel
      wall cross-sectional area. In those animals, CA lumen size was unaltered by
      reducing blood flow, as was CA structure in normotensive animals. The greater
      hypertrophy in the hypertensive animals with reduced blood flow was associated
      with enhanced smooth muscle cell (SMC) proliferation 3 days after the hemodynamic
      changes were induced. There also appeared to be more extensive remodeling of the
      endothelium in the hypertensive animals with normal flow; this was indicated by
      the greater frequency of apoptotic endothelial cells at that time. This reduction
      in blood flow also attenuated endothelial cell nitric oxide synthase expression
      in hypertensive animals but not in normotensive animals. Severe reductions in
      blood flow ( approximately 90%) were required to reduce endothelial cell nitric
      oxide synthase in the normotensive animals. Increasing CA nitric oxide levels by
      perivascular application of S-nitroso-N-acetylpenicillamine (SNAP) to the CAs of
      hypertensive animals with reduced endothelial cell nitric oxide synthase
      attenuated the greater SMC proliferation. Thus, reduced blood flow in
      hypertensive animals promotes hypertrophy by enhancing SMC proliferation via
      mechanisms that reduce the inhibitory effects of nitric oxide on SMC
      proliferation.

PMID- 10904019
TI  - Mechanisms of reduced nitric oxide/cGMP-mediated vasorelaxation in transgenic
      mice overexpressing endothelial nitric oxide synthase.
AB  - NO, constitutively produced by endothelial NO synthase (eNOS), plays a key
      regulatory role in vascular wall homeostasis. We generated transgenic (Tg) mice
      overexpressing eNOS in the endothelium and reported the presence of reduced NO
      elicited relaxation. The purpose of this study was to clarify mechanisms of the
      reduced response to NO-mediated vasodilators in eNOS-Tg mice. Thoracic aortas of
      Tg and control mice were surgically isolated for vasomotor studies. Relaxations
      to acetylcholine and sodium nitroprusside were significantly reduced in Tg
      vessels compared with control vessels. Relaxations to atrial natriuretic peptide
      and 8-bromo-cGMP were also significantly reduced in Tg vessels. Reduced
      relaxations to these agents were restored by chronic N(G)-nitro-L-arginine methyl
      ester treatment. Basal cGMP levels of aortas were higher in Tg mice than in
      control mice, whereas soluble guanylate cyclase (sGC) activity in Tg vessels was
      approximately 50% of the activity in control vessels. Moreover, cGMP-dependent
      protein kinase (PKG) protein levels and PKG enzyme activity were decreased in Tg
      vessels. These observations indicate that chronic overexpression of eNOS in the
      endothelium resulted in resistance to the NO/cGMP-mediated vasodilators and that
      at least 2 distinct mechanisms might be involved: one is reduced sGC activity,
      and the other is a decrease in PKG protein levels. We reported for the first time
      that increased NO release from the endothelium reduces sGC and PKG activity in
      mice. These data may provide a new insight into the mechanisms of nitrate
      tolerance and cross tolerance to nitrovasodilators.

PMID- 10904020
TI  - Molecular plasticity of vascular wall during N(G)-nitro-L-arginine methyl ester
      induced hypertension: modulation of proinflammatory signals.
AB  - It has previously been reported that hypertension induced by the chronic blockade
      of NO production is characterized by a proinflammatory phenotype of the arterial
      wall associated with a periarterial accumulation of inflammatory cells. In the
      present study, the cellular and molecular mechanisms involved in the luminal and
      perivascular accumulation of inflammatory cells were evaluated in the aortas of
      N(G)-nitro-L-arginine methyl ester (L-NAME)-treated rats. Because the medial
      layer remains intact, putative markers of the resistance of the vascular wall to
      cell migration and to oxidative stress were also explored. For this purpose,
      monocyte adhesion, cytokine expression, superoxide anion production, and nuclear
      factor-kappa B (NF-kappa B) activation were assessed in the aortas of L-NAME
      treated rats. Expressions of tissue inhibitor of metalloproteinases-1 (TIMP-1)
      and heme oxygenase-1 (HO-1) in the aortic wall were also studied as possible
      markers of such resistance. Chronic blockade of NO production increased ex vivo
      monocyte adhesion to the endothelium, increased the production of superoxide
      anions, and activated the NF-kappa B system. In concert with this modification of
      the redox state of the vascular wall in L-NAME-treated rats, the expression of
      proinflammatory cytokines interleukin-6, monocyte chemoattractant protein-1, and
      macrophage colony-stimulating factor was increased. In parallel, expressions of
      both TIMP-1 and HO-1 were increased. All these changes were prevented by
      treatment with an angiotensin-converting enzyme inhibitor (Zofenopril).
      Hypertension associated with a proinflammatory phenotype of the vascular wall
      induced by blockade of NO production could be due to an increase in oxidative
      stress, which, in turn, activates the NF-kappa B system and increases gene
      expression. In parallel, the arterial wall overexpresses factors such as TIMP-1
      and HO-1, which could participate in the resistance to cell migration and
      oxidative stress.

PMID- 10904021
TI  - DNA synthesis and apoptosis in smooth muscle cells from a model of genetic
      hypertension.
AB  - The present study was designed to assess vascular smooth muscle cell (VSMC)
      proliferation and apoptosis in primary cultured VSMCs prepared from the aortic
      tunica media of adult (4 to 5 months old) age- and gender-matched groups of
      stroke-prone spontaneously hypertensive rats (SHRSP) and the normotensive
      reference strain, Wistar-Kyoto (WKY) rats. In the present study, VSMC
      proliferation was assessed with measurement of DNA synthesis in response to
      stimulation of G(0)/G(1) arrested VSMCs with 10% serum, whereas apoptosis was
      measured in response to serum deprivation. Apoptosis in aortic VSMCs was assessed
      in vitro with the technique of Annexin V binding in combination with propidium
      iodide exclusion with bivariate flow cytometric analysis. The percentage of
      necrotic VSMCs in the cell populations was assessed simultaneously. The light
      scattering properties of the cells were assessed to provide further information
      on cell shrinkage and chromatin condensation. Results of the present study have
      shown enhanced DNA synthesis in VSMCs from SHRSP (n=10; 5.2+/-0.9 cpmx10(3)/mg
      protein) compared with WKY (n=12; 2.4+/-0.7 cpmx10(3) /mg protein; P<0.05, 95%
      CI, -5271 to -296). In addition, the results of the present study have
      demonstrated the role of serum in the survival of VSMCs in vitro, because SHRSP
      VSMCs underwent significantly more apoptosis in response to insult by serum
      deprivation (n=13; 10.21+/-1.8%) than WKY VSMCs (n=7; 3.44+/-1.4%; P<0.01, 95%
      CI, -11.5 to -2.0). Thus, it appears that both proliferation and apoptosis are
      enhanced in synthetic phenotype aortic medial VSMCs from the SHRSP in vitro.

PMID- 10904022
TI  - Effects of the N-terminal sequence of ACE on the properties of its C-domain.
AB  - Angiotensin I-converting enzyme (ACE, kininase II) has 2 active domains (N and C)
      in a single peptide chain. Because we found its N-domain more stable than its C
      domain, we investigated the effect of the amino-terminus of human ACE on the C
      domain with a molecular construct expressed in Chinese hamster ovary cells (CHO)
      cells and transiently in HEK293 cells. This active N-deleted ACE contained only
      the first 141 amino acids of the human N-domain but not its active center and was
      linked to the active C-domain containing the transmembrane and cytosolic portions
      of ACE. The CHO cells were also transfected with human B(2) bradykinin receptor.
      ACE inhibitors (5 nmol/L or 1 micromol/L) augmented bradykinin (100 nmol/L)
      effects, elevated B(2) receptor numbers, and resensitized the receptor
      desensitized by agonist as measured by arachidonic acid release or [Ca(2+)](i)
      mobilization. Arachidonic acid release was mediated by pertussis toxin-sensitive
      G alpha(i), and [Ca(2+)](i) mobilization was mediated by pertussis-insensitive G
      alpha(q) protein receptor complex. The properties of the construct were compared
      with wild-type ACE and separate N- and C-domains. The N-deleted ACE differed from
      wild-type in activation by Cl(-) and [SO(4)](2-) ions, hydrolysis ratios of
      substrates (both short synthetic and endogenous peptides) and heat stability.
      Thus, the N-terminal peptide of ACE affected the characteristics of the C-domain
      active center. ACE inhibitors acting on N-deleted ACE, which had only a single C
      domain active center anchored to plasma membrane, induced cross-talk between the
      enzyme and the B(2) receptor (eg, the inhibitors resensitized the receptor)
      independent of blocking bradykinin inactivation.

PMID- 10904023
TI  - Effect of angiotensin II antagonist eprosartan on hyperglycemia-induced
      activation of intrarenal renin-angiotensin system in healthy humans.
AB  - We have previously reported that hyperglycemia in healthy human subjects
      increased the renal vasodilator response to the angiotensin-converting enzyme
      inhibitor captopril. This observation raised intriguing possibilities relevant to
      the pathogenesis of nephropathy in patients with diabetes mellitus. To ascertain
      whether the effect of captopril was indeed mediated by a reduction in angiotensin
      II (Ang II) formation, we performed another study in which an Ang II antagonist,
      eprosartan, was used in place of captopril. Nine healthy subjects were studied in
      high sodium balance (ie, sodium intake 200 mmol/d). On the first day, the
      subjects received 600 mg eprosartan orally, and renal plasma flow (RPF) and
      glomerular filtration rate (GFR) were measured. Glucose was infused intravenously
      on the second and third study days to increase plasma glucose to a level below
      the threshold for glycosuria ( approximately 8.8 mmol/L). Eprosartan at a dose of
      600 mg or placebo was administered randomly on the second or third study day 1
      hour after initiation of glucose infusion. RPF increased (by 76+/-7 mL. min(-1).
      1.73 m(-2), P<0.01) in response to sustained moderate hyperglycemia and then
      increased further (by 147+/-15 mL. min(-1). 1. 73 m(-2), P<0.01) when eprosartan
      was administered during hyperglycemia. Eprosartan, conversely, did not affect RPF
      and GFR in normoglycemic subjects. GFR was not affected by either hyperglycemia
      or eprosartan. Neither plasma renin activity nor plasma Ang II concentration
      changed during hyperglycemia, suggesting that the hormonal responses responsible
      for the enhanced renal vasodilator response to eprosartan occurred within the
      kidney. The enhancement of the renal vasodilator effect of eprosartan during
      hyperglycemia is consistent with activation of the intrarenal renin-angiotensin
      system.

PMID- 10904025
TI  - Bradykinin B(2) receptor antagonism attenuates blood pressure response to acute
      angiotensin-converting enzyme inhibition in normal men.
AB  - The physiological effects of angiotensin-converting enzyme (ACE) inhibition may
      be in part mediated by bradykinin. We investigated the effect of coadministration
      of the specific bradykinin B(2) receptor antagonist icatibant on hemodynamic and
      neurohormonal responses to acute intravenous ACE inhibition in normal men on a
      normal sodium diet. We performed a 4-phase, double-blind, double-dummy, placebo
      controlled study in 12 male volunteers. The bradykinin antagonist icatibant (10
      mg IV) was coadministered over the first 15 minutes of a 2-hour infusion of the
      ACE inhibitor perindoprilat (1.5 mg IV). Perindoprilat inhibited ACE activity and
      elicited the expected changes in active renin concentration and angiotensin
      peptides. Over the 3 hours after the start of drug infusion, perindoprilat
      lowered and icatibant increased mean arterial blood pressure (each P<0.0005
      versus placebo). Coadministration of icatibant attenuated the mean arterial blood
      pressure response to perindoprilat (P<0.0005) but had no effect on neurohormonal
      responses to perindoprilat. Our study indicates that the bradykinin B(2) receptor
      antagonist icatibant attenuates the short-term blood pressure-lowering effect of
      acute ACE inhibition in normal men on a normal sodium diet. Bradykinin B(2)
      receptor antagonism alone increases resting blood pressure. Bradykinin may be
      involved in the control of blood pressure in the resting state in humans.

PMID- 10904024
TI  - Bradykinin B(2) receptor gene polymorphism is associated with angiotensin
      converting enzyme inhibitor-related cough.
AB  - The appearance of cough in association with angiotensin-converting enzyme (ACE)
      inhibitors is thought to be related to bradykinin, and it has been speculated
      that the elicitation of adverse effects is genetically predetermined. Several
      polymorphisms of the human bradykinin B(2) receptor gene may be involved in ACE
      inhibitor-related cough. To investigate this possibility, we identified the -58
      thymine (T)/cytosine (C) polymorphism in subjects with ACE inhibitor-related
      cough. We classified the study population into 4 groups: subjects with and
      without cough that were treated with ACE inhibitors (n=30/30), nontreated
      essential hypertensive subjects (n=100), and normotensive subjects (n=100). The 
      58T/C was genotyped by the polymerase chain reaction single-strand conformation
      polymorphism method. The frequencies of the CC genotype and C allele of -58T/C
      were significantly higher in the nontreated hypertensive subjects than in the
      normotensive subjects. Conversely, the frequencies of the TT genotype and T
      allele were significantly higher in the subjects with cough than in the subjects
      without cough. These tendencies were more pronounced in females. Among the
      promoter assays of the human bradykinin B(2) receptor, -58T was found to have a
      higher transcription rate than that of -58C. This finding seems to suggest that
      the transcriptional activity of promoter might be involved in the appearance of
      ACE inhibitor-related cough. A genetic variant of the bradykinin receptor is
      involved in the elicitation of ACE inhibitor-related cough. It may be possible to
      predict the side effects of ACE inhibitors in advance.

PMID- 10904026
TI  - Hypertension risk status and effect of caffeine on blood pressure.
AB  - We compared the acute effects of caffeine on arterial blood pressure (BP) in 5
      hypertension risk groups composed of a total of 182 men. We identified 73 men
      with optimal BP, 28 with normal BP, 36 with high-normal BP, and 27 with stage 1
      hypertension on the basis of resting BP; in addition, we included 18 men with
      diagnosed hypertension from a hypertension clinic. During caffeine testing, BP
      was measured after 20 minutes of rest and again at 45 to 60 minutes after the
      oral administration of caffeine (3.3 mg/kg or a fixed dose of 250 mg for an
      average dose of 260 mg). Caffeine raised both systolic and diastolic BP (SBP and
      DBP, respectively; P<0.0001 for both) in all groups. However, an ANCOVA revealed
      that the strongest response to caffeine was observed among diagnosed men,
      followed by the stage 1 and high-normal groups and then by the normal and optimal
      groups (SBP F(4),(175)=5.06, P<0.0001; DBP F(4,175)=3.02, P<0.02). Indeed,
      diagnosed hypertensive men had a pre-to-postdrug change in BP that was >1.5 times
      greater than the optimal group. The potential clinical relevance of caffeine
      induced BP changes is seen in the BPs that reached the hypertensive range (SBP
      >/=140 mm Hg or DBP >/=90 mm Hg) after caffeine. During the predrug baseline, 78%
      of diagnosed hypertensive men and 4% of stage 1 men were hypertensive, whereas no
      others were hypertensive. After caffeine ingestion, 19% of the high-normal, 15%
      of the stage 1, and 89% of the diagnosed hypertensive groups fell into the
      hypertensive range. All subjects from the optimal and normal groups remained
      normotensive. We conclude that hypertension risk status should take priority in
      future research regarding pressor effects of dietary intake of caffeine.

PMID- 10904027
TI  - Induction of oxidative stress by glutathione depletion causes severe hypertension
      in normal rats.
AB  - Several recent studies have shown that certain forms of genetic or acquired
      hypertension are associated with oxidative stress and that animals with those
      types of hypertension respond favorably to antioxidant therapy. We hypothesize
      that oxidative stress may cause hypertension via (among other mechanisms)
      enhanced oxidation and inactivation of nitric oxide (NO). To test this
      hypothesis, Sprague-Dawley rats were subjected to oxidative stress by glutathione
      (GSH) depletion by means of the GSH synthase inhibitor buthionine sulfoximine
      (BSO, 30 mmol/L in drinking water) for 2 weeks. The control group was given drug
      free drinking water. In parallel experiments, subgroups of animals were provided
      vitamin E-fortified chow and vitamin C-supplemented drinking water. The BSO
      treated group showed a 3-fold decrease in tissue GSH content, a marked elevation
      in blood pressure, and a significant reduction in the urinary excretion of the NO
      metabolite nitrate plus nitrite, which suggests depressed NO availability. These
      characteristics were associated with a significant accumulation in various
      tissues of nitrotyrosine, which is the footprint of NO inactivation by reactive
      oxygen species. Administration of vitamin E plus vitamin C ameliorated
      hypertension, improved urinary nitrate-plus-nitrite excretion, and mitigated
      nitrotyrosine accumulation (despite GSH depletion) in the BSO-treated animals but
      had no effect in the control group. In conclusion, GSH depletion resulted in
      perturbation of the NO system and severe hypertension in normal animals. The
      effects of BSO were mitigated by concomitant antioxidant therapy despite GSH
      depletion, which supports the notion that oxidative stress was involved in the
      pathogenesis of hypertension in this model.

PMID- 10904028
TI  - Highlighted topics series: physiology of a microgravity environment.

PMID- 10904029
TI  - Effects of collagenase and elastase on the mechanical properties of lung tissue
      strips.
AB  - The dynamic stiffness (H), damping coefficient (G), and harmonic distortion
      (k(d)) characterizing tissue nonlinearity of lung parenchymal strips from guinea
      pigs were assessed before and after treatment with elastase or collagenase
      between 0.1 and 3.74 Hz. After digestion, data were obtained both at the same
      mean length and at the same mean force of the strip as before digestion. At the
      same mean length, G and H decreased by approximately 33% after elastase and by
      approximately 47% after collagenase treatment. At the same mean force, G and H
      increased by approximately 7% after elastase and by approximately 25% after
      collagenase treatment. The k(d) increased more after collagenase (40%) than after
      elastase (20%) treatment. These findings suggest that, after digestion, the
      fraction of intact fibers decreases, which, at the same mean length, leads to a
      decrease in moduli. At the same mean force, collagen fibers operate at a higher
      portion of their stress-strain curve, which results in an increase in moduli.
      Also, G and H were coupled so that hysteresivity (G/H) did not change after
      treatments. However, k(d) was decoupled from elasticity and was sensitive to
      stretching of collagen, which may be of value in detecting structural alterations
      in the connective tissue of the lung.

PMID- 10904030
TI  - Shape of the canine diaphragm.
AB  - In an earlier study (Angelillo M, Boriek AM, Rodarte JR, and Wilson TA. J Appl
      Physiol 83: 1486-1491, 1997), we proposed a mathematical theory for the structure
      and shape of the diaphragm. Muscle bundles were assumed to lie on lines that are
      simultaneously geodesics and lines of principal curvature of the diaphragm
      surface, and the class of surfaces that are formed by line elements that are both
      geodesics and lines of principal curvature was described. Here we present data on
      the shape of the canine diaphragm that were obtained by the radiopaque marker
      technique, and we describe a surface that fits the data and satisfies the
      requirements of the theory. The costal and crural diaphragms are fit by cyclides
      with radii of 3.7 and 2.3 cm, respectively. In addition, the theory is extended
      to include the description of a joint between cyclides, and the observed
      properties of the joint between the costal and crural diaphragms at the dorsal
      end of the costal diaphragm match those required by the theory.

PMID- 10904031
TI  - Chronically and acutely exercised rats: biomarkers of oxidative stress and
      endogenous antioxidants.
AB  - The responses to oxidative stress induced by chronic exercise (8-wk treadmill
      running) or acute exercise (treadmill running to exhaustion) were investigated in
      the brain, liver, heart, kidney, and muscles of rats. Various biomarkers of
      oxidative stress were measured, namely, lipid peroxidation [malondialdehyde
      (MDA)], protein oxidation (protein carbonyl levels and glutamine synthetase
      activity), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine), and endogenous
      antioxidants (ascorbic acid, alpha-tocopherol, glutathione, ubiquinone,
      ubiquinol, and cysteine). The predominant changes are in MDA, ascorbic acid,
      glutathione, cysteine, and cystine. The mitochondrial fraction of brain and liver
      showed oxidative changes as assayed by MDA similar to those of the tissue
      homogenate. Our results show that the responses of the brain to oxidative stress
      by acute or chronic exercise are quite different from those in the liver, heart,
      fast muscle, and slow muscle; oxidative stress by acute or chronic exercise
      elicits different responses depending on the organ tissue type and its endogenous
      antioxidant levels.

PMID- 10904032
TI  - Operation Everest III: role of plasma volume expansion on VO(2)(max) during
      prolonged high-altitude exposure.
AB  - We hypothesize that plasma volume decrease (DeltaPV) induced by high-altitude
      (HA) exposure and intense exercise is involved in the limitation of maximal O(2)
      uptake (VO(2)(max)) at HA. Eight male subjects were decompressed for 31 days in a
      hypobaric chamber to the barometric equivalent of Mt. Everest (8,848 m). Maximal
      exercise was performed with and without plasma volume expansion (PVX, 219-292 ml)
      during exercise, at sea level (SL), at HA (370 mmHg, equivalent to 6, 000 m after
      10-12 days) and after return to SL (RSL, 1-3 days). Plasma volume (PV) was
      determined at rest at SL, HA, and RSL by Evans blue dilution. PV was decreased by
      26% (P < 0.01) at HA and was 10% higher at RSL than at SL. Exercise-induced
      DeltaPV was reduced both by PVX and HA (P < 0.05). Compared with SL, VO(2)(max)
      was decreased by 58 and 11% at HA and RSL, respectively. VO(2)(max) was enhanced
      by PVX at HA (+9%, P < 0.05) but not at SL or RSL. The more PV was decreased at
      HA, the more VO(2)(max) was improved by PVX (P < 0.05). At exhaustion, plasma
      renin and aldosterone were not modified at HA compared with SL but were higher at
      RSL, whereas plasma atrial natriuretic factor was lower at HA. The present
      results suggest that PV contributes to the limitation of VO(2)(max) during
      acclimatization to HA. RSL-induced PVX, which may be due to increased activity of
      the renin-aldosterone system, could also influence the recovery of VO(2)(max).

PMID- 10904034
TI  - Sustained isocapnic hypoxia suppresses the perception of the magnitude of
      inspiratory resistive loads.
AB  - The sensation of increased respiratory resistance or effort is likely to be
      important for the initiation of alerting or arousal responses, particularly in
      sleep. Hypoxia, through its central nervous system-depressant effects, may
      decrease the perceived magnitude of respiratory loads. To examine this, we
      measured the effect of isocapnic hypoxia on the ability of 10 normal, awake males
      (mean age = 24.0 +/- 1.8 yr) to magnitude-scale five externally applied
      inspiratory resistive loads (mean values from 7.5 to 54.4 cmH(2)O. l(-1). s).
      Each subject scaled the loads during 37 min of isocapnic hypoxia (inspired O(2)
      fraction = 0.09, arterial O(2) saturation of approximately 80%) and during 37 min
      of normoxia, using the method of open magnitude numerical scaling. Results were
      normalized by modulus equalization to allow between-subject comparisons. With the
      use of peak inspiratory pressure (PIP) as the measure of load stimulus magnitude,
      the perception of load magnitude (Psi) increased linearly with load and, averaged
      for all loaded breaths, was significantly lower during hypoxia than during
      normoxia (20.1 +/- 0.9 and 23.9 +/- 1.3 arbitrary units, respectively; P = 0.
      048). Psi declined with time during hypoxia (P = 0.007) but not during normoxia
      (P = 0.361). Our result is remarkable because PIP was higher at all times during
      hypoxia than during normoxia, and previous studies have shown that an elevation
      in PIP results in increased Psi. We conclude that sustained isocapnic hypoxia
      causes a progressive suppression of the perception of the magnitude of
      inspiratory resistive loads in normal subjects and could, therefore, impair
      alerting or arousal responses to respiratory loading.

PMID- 10904033
TI  - Sprint training normalizes Ca(2+) transients and SR function in postinfarction
      rat myocytes.
AB  - Previous studies have shown that myocytes isolated from sedentary (Sed) rat
      hearts 3 wk after myocardial infarction (MI) undergo hypertrophy, exhibit altered
      intracellular Ca(2+) concentration ([Ca(2+)](i)) dynamics and abnormal
      contraction, and impaired sarcoplasmic reticulum (SR) function manifested as
      prolonged half-time of [Ca(2+)](i) decline. Because exercise training elicits
      positive adaptations in cardiac contractile function and myocardial Ca(2+)
      regulation, the present study examined whether 6-8 wk of high-intensity sprint
      training (HIST) would restore [Ca(2+)](i) dynamics and SR function in MI myocytes
      toward normal. In MI rats, HIST ameliorated myocyte hypertrophy as indicated by
      significant (P </= 0.05) decreases in whole cell capacitances [Sham-Sed 179 +/-12
      (n = 20); MI-Sed 226 +/- 7 (n = 20); MI-HIST 183 +/- 11 pF (n = 19)]. HIST
      significantly (P < 0.0001) restored both systolic [Ca(2+)](i) [Sham-Sed 421 +/- 9
      (n = 79); MI-Sed 350 +/- 6 (n = 70); MI-HIST 399 +/- 9 nM (n = 70)] and half-time
      of [Ca(2+)](i) decline (Sham-Sed 0. 197 +/- 0.005; MI-Sed 0.247 +/- 0.006; MI
      HIST 0.195 +/- 0.006 s) toward normal. Compared with Sham-Sed myocytes, SR Ca(2+)
      ATPase expression significantly (P < 0.001) decreased by 44% in MI-Sed myocytes.
      Surprisingly, expression of SR Ca(2+)-ATPase was further reduced in MI-HIST
      myocytes to 26% of that measured in Sham-Sed myocytes. There were no differences
      in calsequestrin expression among the three groups. Expression of phospholamban
      was not different between Sham-Sed and MI-Sed myocytes but was significantly (P <
      0.01) reduced in MI-HIST myocytes by 25%. Our results indicate that HIST
      instituted shortly after MI improves [Ca(2+)](i) dynamics in surviving myocytes.
      Improvement in SR function by HIST is mediated not by increased SR Ca(2+)-ATPase
      expression, but by modulating phospholamban regulation of SR Ca(2+)-ATPase
      activity.

PMID- 10904035
TI  - Water balance in rats exposed to chronic centrifugation.
AB  - Changes in gravitational load have been shown to alter renal function, which
      could potentially affect water balance. Therefore, the present study was
      conducted to determine the effects of chronic centrifugation on water balance.
      Eight Sprague-Dawley rats were centrifuged (12 days at 2 G), and eight rats were
      used as a control group. Water balance over the course of the study was
      determined by quantifying the percentage (%) of total body water [TBW; (TBW/body
      mass)] and water flux (water consumption - urine volume). TBW was estimated, by
      means of deuterium oxide dilution, before the study and after 3 days of
      centrifugation and by means of desiccation after 12 days of centrifugation. %TBW
      did not change in the centrifuged rats from initial levels or relative to
      controls over the course of the study. Differences between the sum of water
      consumption and sum of urine volume for the 12-day period were the same in both
      groups. Although an initial period of negative water balance was observed, the
      lack of a change in %TBW among the three measurement periods or in water flux
      over the 12 days of centrifugation suggests that water balance is not negatively
      affected as a result of centrifugation at 2 G.

PMID- 10904036
TI  - Coactivation of the antagonist muscle does not covary with steadiness in old
      adults.
AB  - The purpose of the study was to determine the association between steadiness and
      activation of the agonist and antagonist muscles during isometric and anisometric
      contractions. Young (n = 14) and old (n = 15) adults used the first dorsal
      interosseus muscle to perform constant-force and constant-load tasks (2.5, 5, 20,
      50, and 75% maximum) with the left index finger. Steadiness was quantified as the
      coefficient of variation of force and the SD of acceleration normalized to the
      load lifted. The old adults were less steady at most target forces with isometric
      contractions (2.5, 5, and 50%) and with most loads during the anisometric
      contractions (2.5, 5, and 20%). Furthermore, the old adults were less steady when
      performing lengthening contractions (up to 50%) compared with shortening
      contractions, whereas there was no difference for young adults. The reduced
      steadiness exhibited by the old adults during these tasks was not associated with
      differences in the average level of agonist muscle electromyogram or with
      coactivation of the antagonist muscle.

PMID- 10904037
TI  - PLA(2) dependence of diaphragm mitochondrial formation of reactive oxygen
      species.
AB  - Contraction-induced respiratory muscle fatigue and sepsis-related reductions in
      respiratory muscle force-generating capacity are mediated, at least in part, by
      reactive oxygen species (ROS). The subcellular sources and mechanisms of
      generation of ROS in these conditions are incompletely understood. We postulated
      that the physiological changes associated with muscle contraction (i.e.,
      increases in calcium and ADP concentration) stimulate mitochondrial generation of
      ROS by a phospholipase A(2) (PLA(2))-modulated process and that sepsis enhances
      muscle generation of ROS by upregulating PLA(2) activity. To test these
      hypotheses, we examined H(2)O(2) generation by diaphragm mitochondria isolated
      from saline-treated control and endotoxin-treated septic animals in the presence
      and absence of calcium and ADP; we also assessed the effect of PLA(2) inhibitors
      on H(2)O(2) formation. We found that 1) calcium and ADP stimulated H(2)O(2)
      formation by diaphragm mitochondria from both control and septic animals; 2)
      mitochondria from septic animals demonstrated substantially higher H(2)O(2)
      formation than mitochondria from control animals under basal, calcium-stimulated,
      and ADP-stimulated conditions; and 3) inhibitors of 14-kDa PLA(2) blocked the
      enhanced H(2)O(2) generation in all conditions. We also found that administration
      of arachidonic acid (the principal metabolic product of PLA(2) activation)
      increased mitochondrial H(2)O(2) formation by interacting with complex I of the
      electron transport chain. These data suggest that diaphragm mitochondrial ROS
      formation during contraction and sepsis may be critically dependent on PLA(2)
      activation.

PMID- 10904038
TI  - Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr.
AB  - We employed a whole body magnetic resonance imaging protocol to examine the
      influence of age, gender, body weight, and height on skeletal muscle (SM) mass
      and distribution in a large and heterogeneous sample of 468 men and women. Men
      had significantly (P < 0.001) more SM in comparison to women in both absolute
      terms (33.0 vs. 21.0 kg) and relative to body mass (38.4 vs. 30.6%). The gender
      differences were greater in the upper (40%) than lower (33%) body (P < 0.01). We
      observed a reduction in relative SM mass starting in the third decade; however, a
      noticeable decrease in absolute SM mass was not observed until the end of the
      fifth decade. This decrease was primarily attributed to a decrease in lower body
      SM. Weight and height explained approximately 50% of the variance in SM mass in
      men and women. Although a linear relationship existed between SM and height, the
      relationship between SM and body weight was curvilinear because the contribution
      of SM to weight gain decreased with increasing body weight. These findings
      indicate that men have more SM than women and that these gender differences are
      greater in the upper body. Independent of gender, aging is associated with a
      decrease in SM mass that is explained, in large measure, by a decrease in lower
      body SM occurring after the fifth decade.

PMID- 10904039
TI  - Effect of the mechanical ventilatory cycle on thermodilution right ventricular
      volumes and cardiac output.
AB  - The purpose of this study was to evaluate right ventricular (RV) loading and
      cardiac output changes, by using the thermodilution technique, during the
      mechanical ventilatory cycle. Fifteen critically ill patients on mechanical
      ventilation, with 5 cmH(2)O of positive end-expiratory pressure, mean respiratory
      frequency of 18 breaths/min, and mean tidal volume of 708 ml, were studied with
      help of a rapid-response thermistor RV ejection fraction pulmonary artery
      catheter, allowing 5-ml room-temperature 5% isotonic dextrose thermodilution
      measurements of cardiac index (CI), stroke volume (SV) index, RV ejection
      fraction (RVEF), RV end-diastolic volume (RVEDV), and RV end-systolic volume
      (RVESV) indexes at 10% intervals of the mechanical ventilatory cycle. The
      ventilatory modulation of CI and RV volumes varied from patient to patient, and
      the interindividual variability was greater for the latter variables. Within
      patients also, RV volumes were modulated more by the ventilatory cycle than CI
      and SV index. Around a mean value of 3.95 +/- 1.18 l. min(-1). m(-2) (= 100%), CI
      varied from 87.3 +/- 5.2 (minimum) to 114.3 +/- 5.1% (maximum), and RVESV index
      varied between 61.5 +/- 17.8 and 149.3 +/- 34.1% of mean 55.1 +/- 17.9 ml/m(2)
      during the ventilatory cycle. The variations in the cycle exceeded the
      measurement error even though the latter was greater for RVEF and volumes than
      for CI and SV index. For mean values, there was an inspiratory decrease in RVEF
      and increase in RVESV, whereas a rise in RVEDV largely prevented a fall in SV
      index. We conclude that cyclic RV afterloading necessitates multiple
      thermodilution measurements equally spaced in the ventilatory cycle for reliable
      assessment of RV performance during mechanical ventilation of patients.

PMID- 10904040
TI  - Effects of hormone replacement therapy on hemodynamic responses of postmenopausal
      women to passive heating.
AB  - To examine the influence of chronic hormone replacement therapy (HRT) on the
      central and peripheral cardiovascular responses of postmenopausal women to direct
      passive heating, seven women taking estrogen replacement therapy, seven women
      taking estrogen and progesterone therapy, and seven women not taking HRT were
      passively heated with water-perfused suits to their individual limit of thermal
      tolerance. Measurements included heart rate (HR), cardiac output, blood pressure,
      skin blood flow, splanchnic blood flow, renal blood flow, esophageal temperature,
      and mean skin temperature. Cardiac output was higher in women taking estrogen and
      progesterone therapy than in women not taking HRT (7.12 +/- 0.70 vs. 5.02 +/- 0.
      57 l/min at the limit of thermal tolerance, respectively; P < 0.05) because of a
      higher HR. However, when the HR data were plotted as a percentage of the maximum
      HR or percentage of HR reserve, there were no differences among the three groups
      of women. Neither splanchnic nor renal blood flow differed among the groups of
      women. These data suggest that HRT has little effect on the cardiovascular
      responses to direct passive heating.

PMID- 10904041
TI  - Skeletal muscle attenuation determined by computed tomography is associated with
      skeletal muscle lipid content.
AB  - The purpose of this investigation was to validate that in vivo measurement of
      skeletal muscle attenuation (MA) with computed tomography (CT) is associated with
      muscle lipid content. Single-slice CT scans performed on phantoms of varying
      lipid concentrations revealed good concordance between attenuation and lipid
      concentration (r(2) = 0.995); increasing the phantom's lipid concentration by 1
      g/100 ml decreased its attenuation by approximately 1 Hounsfield unit (HU). The
      test-retest coefficient of variation for two CT scans performed in six volunteers
      was 0.51% for the midthigh and 0.85% for the midcalf, indicating that the
      methodological variability is low. Lean subjects had significantly higher (P <
      0.01) MA values (49.2 +/- 2.8 HU) than did obese nondiabetic (39.3 +/- 7.5 HU)
      and obese Type 2 diabetic (33.9 +/- 4. 1 HU) subjects, whereas obese Type 2
      diabetic subjects had lower MA values that were not different from obese
      nondiabetic subjects. There was also good concordance between MA in midthigh and
      midcalf (r = 0.60, P < 0.01), psoas (r = 0.65, P < 0.01), and erector spinae (r =
      0.77, P < 0.01) in subsets of volunteers. In 45 men and women who ranged from
      lean to obese (body mass index = 18.5 to 35.9 kg/m(2)), including 10 patients
      with Type 2 diabetes mellitus, reduced MA was associated with increased muscle
      fiber lipid content determined with histological oil red O staining (P = -0.43, P
      < 0. 01). In a subset of these volunteers (n = 19), triglyceride content in
      percutaneous biopsy specimens from vastus lateralis was also associated with MA
      (r = -0.58, P = 0.019). We conclude that the attenuation of skeletal muscle in
      vivo determined by CT is related to its lipid content and that this noninvasive
      method may provide additional information regarding the association between
      muscle composition and muscle function.

PMID- 10904042
TI  - Postischemic recovery of heart metabolism and function: role of mitochondrial
      fatty acid transfer.
AB  - Postischemic recovery of contractile function is better in hearts from fasted
      rats than in hearts from fed rats. In this study, we examined whether feeding
      induced inhibition of palmitate oxidation at the level of carnitine palmitoyl
      transferase I is involved in the mechanism underlying impaired recovery of
      contractile function. Hearts isolated from fasted or fed rats were submitted to
      no-flow ischemia followed by reperfusion with buffer containing 8 mM glucose and
      either 0.4 mM palmitate or 0.8 mM octanoate. During reperfusion, oxidation of
      palmitate was higher after fasting than after feeding, whereas oxidation of
      octanoate was not influenced by the nutritional state. In the presence of
      palmitate, recovery of left ventricular developed pressure was better in hearts
      from fasted rats. Substitution of octanoate for palmitate during reperfusion
      enhanced recovery of left ventricular developed pressure in hearts from fed rats.
      However, the chain length of the fatty acid did not influence diastolic
      contracture. The results suggest that nutritional variation of mitochondrial
      fatty acid transfer may influence postischemic recovery of contractile function.

PMID- 10904043
TI  - Characterization of pharyngeal resistance during sleep in a spectrum of sleep
      disordered breathing.
AB  - Aims of the study were 1) to compare Hudgel's hyperbolic with Rohrer's polynomial
      model in describing the pressure-flow relationship, 2) to use this pressure-flow
      relationship to describe these resistances and to evaluate the effects of sleep
      stages on pharyngeal resistances, and 3) to compare these resistances to the
      pressure-to-flow ratio (DeltaP/V). We studied 12 patients: three with upper
      airway resistance syndrome (UARS), four with obstructive sleep hypopnea syndrome
      (OSHS), three with obstructive sleep apnea syndrome (OSAS), and two with simple
      snoring (SS). Transpharyngeal pressures were calculated between choanae and
      epiglottis. Flow was measured by use of a pneumotachometer. The pressure-flow
      relationship was established by using nonlinear regression and was appreciated by
      the Pearson's square (r(2)). Mean resistance at peak pressure (Rmax) was
      calculated according to the hyperbolic model during stable respiration. In 78% of
      the cases, the value of r(2) was greater when the hyperbolic model was used. We
      demonstrated that Rmax was in excellent agreement with P/V. UARS patients
      exhibited higher awake mean Rmax than normal subjects and other subgroups and a
      larger increase from wakefulness to slow-wave sleep than subjects with OSAS,
      OSHS, and SS. Analysis of breath-by-breath changes in Rmax was also a sensitive
      method to detect episodes of high resistance during sleep.

PMID- 10904044
TI  - Effects of respiratory muscle work on exercise performance.
AB  - The normal respiratory muscle effort at maximal exercise requires a significant
      fraction of cardiac output and causes leg blood flow to fall. We questioned
      whether the high levels of respiratory muscle work experienced in heavy exercise
      would affect performance. Seven male cyclists [maximal O(2) consumption (VO(2))
      63 +/- 5 ml. kg(-1). min(-1)] each completed 11 randomized trials on a cycle
      ergometer at a workload requiring 90% maximal VO(2). Respiratory muscle work was
      either decreased (unloading), increased (loading), or unchanged (control). Time
      to exhaustion was increased with unloading in 76% of the trials by an average of
      1.3 +/- 0.4 min or 14 +/- 5% and decreased with loading in 83% of the trials by
      an average of 1.0 +/- 0.6 min or 15 +/- 3% compared with control (P < 0.05).
      Respiratory muscle unloading during exercise reduced VO(2), caused
      hyperventilation, and reduced the rate of change in perceptions of respiratory
      and limb discomfort throughout the duration of exercise. These findings
      demonstrate that the work of breathing normally incurred during sustained, heavy
      intensity exercise (90% VO(2)) has a significant influence on exercise
      performance. We speculate that this effect of the normal respiratory muscle load
      on performance in trained male cyclists is due to the associated reduction in leg
      blood flow, which enhances both the onset of leg fatigue and the intensity with
      which both leg and respiratory muscle efforts are perceived.

PMID- 10904045
TI  - Functional anatomy of the vagal innervation of the cervical trachea of the dog.
AB  - The canine cervical trachea has been used for numerous studies regarding the
      neural control of tracheal smooth muscle. The purpose of the present study was to
      determine whether there is lateral dominance by either the left or right vagal
      innervation of the canine cervical trachea. In anesthetized dogs, pressure in the
      cuff of the endotracheal tube was used as an index of smooth muscle tone in the
      trachea. After establishment of tracheal tone, as indicated by increased cuff
      pressure, either the right or left vagus nerve was sectioned followed by section
      of the contralateral vagus. Sectioning the right vagus first resulted in total
      loss of tone in the cervical trachea, whereas sectioning the left vagus first
      produced either a partial or no decrease in tracheal tone. After bilateral
      section of the vagi, cuff pressure was recorded during electrical stimulation of
      the rostral end of the right or left vagus. At the maximum current strength used,
      stimulation of the left vagus produced tracheal constriction that averaged 28.5%
      of the response to stimulation of the right vagus (9.0 +/- 1.8 and 31.6 +/- 2.5
      mmHg, respectively). In conclusion, the musculature of cervical trachea in the
      dog appears to be predominantly controlled by vagal efferents in the right vagus
      nerve.

PMID- 10904046
TI  - Effect of resistance training on single muscle fiber contractile function in
      older men.
AB  - The purpose of this study was to examine single cell contractile mechanics of
      skeletal muscle before and after 12 wk of progressive resistance training (PRT)
      in older men (n = 7; age = 74 +/- 2 yr and weight = 75 +/- 5 kg). Knee extensor
      PRT was performed 3 days/wk at 80% of one-repetition maximum. Muscle biopsy
      samples were obtained from the vastus lateralis before and after PRT (pre- and
      post-PRT, respectively). For analysis, chemically skinned single muscle fibers
      were studied at 15 degrees C for peak tension [the maximal isometric force
      (P(o))], unloaded shortening velocity (V(o)), and force-velocity parameters. In
      this study, a total of 199 (89 pre- and 110 post-PRT) myosin heavy chain (MHC) I
      and 99 (55 pre- and 44 post-PRT) MHC IIa fibers were reported. Because of the
      minimal number of hybrid fibers identified post-PRT, direct comparisons were
      limited to MHC I and IIa fibers. Muscle fiber diameter increased 20% (83 +/- 1 to
      100 +/- 1 microm) and 13% (86 +/- 1 to 97 +/- 2 microm) in MHC I and IIa fibers,
      respectively (P < 0.05). P(o) was higher (P < 0.05) in MHC I (0.58 +/- 0.02 to
      0.90 +/- 0.02 mN) and IIa (0.68 +/- 0.02 to 0.85 +/- 0.03 mN) fibers. Muscle
      fiber V(o) was elevated 75% (MHC I) and 45% (MHC IIa) after PRT (P < 0.05). MHC I
      and IIa fiber power increased (P < 0.05) from 7.7 +/- 0.5 to 17.6 +/- 0.9 microN.
      fiber lengths. s(-1) and from 25.5 to 41.1 microN. fiber lengths. s(-1),
      respectively. These data indicate that PRT in elderly men increases muscle cell
      size, strength, contractile velocity, and power in both slow- and fast-twitch
      muscle fibers. However, it appears that these changes are more pronounced in the
      MHC I muscle fibers.

PMID- 10904047
TI  - Muscimol dialysis in the retrotrapezoid nucleus region inhibits breathing in the
      awake rat.
AB  - Under anesthesia, inactivation of the retrotrapezoid nucleus (RTN) region
      markedly inhibits breathing and chemoreception. In conscious rats, we dialyzed
      muscimol for 30 min to inhibit neurons of the RTN region reversibly. Dialysis of
      artificial cerebrospinal fluid had no effect. Muscimol (1 or 10 mM) significantly
      decreased tidal volume (VT) (by 16-17%) within 15 min. VT remained decreased for
      50 min or more, with recovery by 90 min. Ventilation (VE) decreased significantly
      (by 15-20%) within 15 min and then returned to baseline within 40 min as a result
      of an increase in frequency. This, we suggest, is a compensatory physiological
      response to the reduced VT. Oxygen consumption was unchanged. In response to 7%
      CO(2) in the 1 mM group, absolute VE and change in VE were significantly reduced
      (by 19-22%). In the 10 mM group, the response to dialysis included a time-related
      increase in frequency and decrease in body temperature, which may reflect greater
      spread of muscimol. In the awake rat, the RTN region provides a portion of the
      tonic drive to breathe, as well as a portion of the response to hypercapnia.

PMID- 10904048
TI  - Effects of age on elastic moduli of human lungs.
AB  - The model of the lung as an elastic continuum undergoing small distortions from a
      uniformly inflated state has been used to describe many lung deformation
      problems. Lung stress-strain material properties needed for this model are
      described by two elastic moduli: the bulk modulus, which describes a uniform
      inflation, and the shear modulus, which describes an isovolume deformation. In
      this study we measured the bulk modulus and shear modulus of human lungs obtained
      at autopsy at several fixed transpulmonary pressures (Ptp). The bulk modulus was
      obtained from small pressure-volume perturbations on different points of the
      deflation pressure-volume curve. The shear modulus was obtained from indentation
      tests on the lung surface. The results indicated that, at a constant Ptp, both
      bulk and shear moduli increased with age, and the increase was greater at higher
      Ptp values. The micromechanical basis for these changes remains to be elucidated.

PMID- 10904049
TI  - Free radical scavenging and antioxidant effects of lactate ion: an in vitro
      study.
AB  - Divergent literature data are found concerning the effect of lactate on free
      radical production during exercise. To clarify this point, we tested the pro- or
      antioxidant effect of lactate ion in vitro at different concentrations using
      three methods: 1) electron paramagnetic resonance (EPR) was used to study the
      scavenging ability of lactate toward the superoxide aion (O(2)(-).) and hydroxyl
      radical (.OH); 2) linoleic acid micelles were employed to investigate the lipid
      radical scavenging capacity of lactate; and 3) primary rat hepatocyte culture was
      used to study the inhibition of membrane lipid peroxidation by lactate. EPR
      experiments exhibited scavenging activities of lactate toward both O(2)(-).
      and.OH; lactate was also able to inhibit lipid peroxidation of hepatocyte
      culture. Both effects of lactate were concentration dependent. However, no
      inhibition of lipid peroxidation by lactate was observed in the micelle model.
      These results suggested that lactate ion may prevent lipid peroxidation by
      scavenging free radicals such as O(2)(-). and.OH but not lipid radicals. Thus
      lactate ion might be considered as a potential antioxidant agent.

PMID- 10904050
TI  - Exercise induces lipoprotein lipase and GLUT-4 protein in muscle independent of
      adrenergic-receptor signaling.
AB  - Exercise increases the expression of lipoprotein lipase (LPL) and GLUT-4 in
      skeletal muscle. Intense exercise increases catecholamines, and catecholamines
      without exercise can affect the expression of both LPL and GLUT-4. To test the
      hypothesis that adrenergic-receptor signaling is central to the induction of LPL
      and GLUT-4 by exercise, six untrained individuals [age 28 +/- 4 (SD) yr, peak
      oxygen uptake 3.6 +/- 0.3 l/min] performed two exercise bouts within 12 days.
      Exercise consisted of cycling at approximately 65% peak oxygen uptake for 60 min
      with (block trial) and without (control trial) adrenergic-receptor blockade.
      Exercise intensity was the same during the block and control trials. Plasma
      catecholamine concentrations were significantly higher and heart rates were
      significantly lower during the block trial compared with the control trial,
      consistent with known effects of adrenergic-receptor blockade. However, blockade
      did not prevent the induction of either LPL or GLUT-4 proteins assayed in
      biopsies of skeletal muscle. LPL was significantly increased by 170-240% and GLUT
      4 was significantly increased by 32-51% at 22 h after exercise compared with
      before exercise during both the control and block trials. These findings provide
      evidence that exercise increases muscle LPL and GLUT-4 protein content via
      signals generated by alterations in cellular homeostasis and not by adrenergic
      receptor stimulation.

PMID- 10904052
TI  - Effect of gender on the development of hypocapnic apnea/hypopnea during NREM
      sleep.
AB  - We hypothesized that a decreased susceptibility to the development of hypocapnic
      central apnea during non-rapid eye movement (NREM) sleep in women compared with
      men could be an explanation for the gender difference in the sleep apnea/hypopnea
      syndrome. We studied eight men (age 25-35 yr) and eight women in the midluteal
      phase of the menstrual cycle (age 21-43 yr); we repeated studies in six women
      during the midfollicular phase. Hypocapnia was induced via nasal mechanical
      ventilation for 3 min, with respiratory frequency matched to eupneic frequency.
      Tidal volume (VT) was increased between 110 and 200% of eupneic control.
      Cessation of mechanical ventilation resulted in hypocapnic central apnea or
      hypopnea, depending on the magnitude of hypocapnia. Nadir minute ventilation in
      the recovery period was plotted against the change in end-tidal PCO(2)
      (PET(CO(2))) per trial; minute ventilation was given a value of 0 during central
      apnea. The apneic threshold was defined as the x-intercept of the linear
      regression line. In women, induction of a central apnea required an increase in
      VT to 155 +/- 29% (mean +/- SD) and a reduction of PET(CO(2)) by -4.72 +/- 0.57
      Torr. In men, induction of a central apnea required an increase in VT to 142 +/-
      13% and a reduction of PET(CO(2)) by -3.54 +/- 0.31 Torr (P = 0.002). There was
      no difference in the apneic threshold between the follicular and the luteal phase
      in women. Premenopausal women are less susceptible to hypocapnic disfacilitation
      during NREM sleep than men. This effect was not explained by progesterone.
      Preservation of ventilatory motor output during hypocapnia may explain the gender
      difference in sleep apnea.

PMID- 10904051
TI  - Preventing mediastinal shift after pneumonectomy does not abolish physiological
      compensation.
AB  - To determine the role of mediastinal shift after pneumonectomy (PNX) on
      compensatory responses, we performed right PNX in adult dogs and replaced the
      resected lung with a custom-shaped inflatable silicone prosthesis. Prosthesis was
      inflated (Inf) to prevent mediastinal shift, or deflated (Def), allowing
      mediastinal shift to occur. Thoracic, lung air, and tissue volumes were measured
      by computerized tomography scan. Lung diffusing capacities for carbon monoxide
      (DL(CO)) and its components, membrane diffusing capacity for carbon monoxide
      (Dm(CO)) and capillary blood volume (Vc), were measured at rest and during
      exercise by a rebreathing technique. In the Inf group, lung air volume was
      significantly smaller than in Def group; however, the lung became elongated and
      expanded by 20% via caudal displacement of the left hemidiaphragm. Consequently,
      rib cage volume was similar, but total thoracic volume was higher in the Inf
      group. Extravascular septal tissue volume was not different between groups. At a
      given pulmonary blood flow, DL(CO) and Dm(CO) were significantly lower in the Inf
      group, but Vc was similar. In one dog, delayed mediastinal shift occurred 9 mo
      after PNX; both lung volume and DL(CO) progressively increased over the
      subsequent 3 mo. We conclude that preventing mediastinal shift after PNX impairs
      recruitment of diffusing capacity but does not abolish expansion of the remaining
      lung or the compensatory increase in extravascular septal tissue volume.

PMID- 10904053
TI  - Forearm muscle metabolism studied using (31)P-MRS during progressive exercise to
      fatigue after Acz administration.
AB  - The effects of acetazolamide (Acz)-induced carbonic anhydrase inhibition (CAI) on
      muscle intracellular thresholds (T) for intracellular pH (pH(i)) and inorganic
      phosphate-to-phosphate creatine ratio (P(i)/PCr) and the plasma lactate (La(-))
      threshold were examined in nine adult male subjects performing forearm wrist
      flexion exercise to fatigue. Exercise consisted of raising and lowering (1-s
      contraction, 1-s relaxation) a cylinder whose volume increased at a rate of 200
      ml/min. The protocol was performed during control (Con) and after 45 min of CAI
      with Acz (10 mg/kg body wt iv). T(pH(i)) and T(P(i)/PCr), determined using (31)P
      labeled magnetic resonance spectroscopy (MRS), were similar in Acz (722 +/- 50
      and 796 +/- 75 mW, respectively) and Con (855 +/- 211 and 835 +/- 235 mW,
      respectively). The pH(i) was similar at end-exercise (6.38 +/- 0.10 Acz and 6.43
      +/- 0.22 Con), but pH(i) recovery was slowed in Acz. In a separate experiment,
      blood was sampled from a deep arm vein at the elbow for determination of plasma
      lactate concentration ([La(-)](pl)) and T(La(-)). [La(-)](pl) was lower (P <
      0.05) in Acz than Con (3.7 +/- 1.7 vs. 5.0 +/- 1.7 mmol/l) at end-exercise and in
      early recovery, but T(La(-)) was higher (1,433 +/- 243 vs. 1,041 +/- 414 mW,
      respectively). These data suggest that the lower [La(-)](pl) seen with CAI was
      not due to a delayed onset or rate of muscle La(-) accumulation but may be
      related to impaired La(-) removal from muscle.

PMID- 10904054
TI  - Impaired sarcoplasmic reticulum Ca(2+) release rate after fatiguing stimulation
      in rat skeletal muscle.
AB  - The purpose of the study was to characterize the sarcoplasmic reticulum (SR)
      function and contractile properties before and during recovery from fatigue in
      the rat extensor digitorum longus muscle. Fatiguing contractions (60 Hz, 150 ms/s
      for 4 min) induced a reduction of the SR Ca(2+) release rate to 66% that
      persisted for 1 h, followed by a gradual recovery to 87% of prefatigue release
      rate at 3 h recovery. Tetanic force and rate of force development (+dF/dt) and
      relaxation (-dF/dt) were depressed by approximately 80% after stimulation.
      Recovery occurred in two phases: an initial phase, in which during the first 0.5
      1 h the metabolic state recovered to resting levels, and a slow phase from 1-3 h
      characterized by a rather slow recovery of the mechanical properties. The
      recovery of SR Ca(2+) release rate was closely correlated to +dF/dt during the
      slow phase of recovery (r(2) = 0.51; P < 0.05). Despite a slowing of the
      relaxation rate, we did not find any significant alterations in the SR Ca(2+)
      uptake function. These data demonstrate that the Ca(2+) release mechanism of SR
      is sensitive to repetitive in vitro muscle contraction. Moreover, the results
      indicate that +dF/dt to some extent depends on the rate of Ca(2+) release during
      the slow phase of recovery.

PMID- 10904055
TI  - Supine lower body negative pressure exercise during bed rest maintains upright
      exercise capacity.
AB  - Bed rest and spaceflight reduce exercise fitness. Supine lower body negative
      pressure (LBNP) treadmill exercise provides integrated cardiovascular and
      musculoskeletal stimulation similar to that imposed by upright exercise in Earth
      gravity. We hypothesized that 40 min of supine exercise per day in a LBNP chamber
      at 1.0-1.2 body wt (58 +/- 2 mmHg LBNP) maintains aerobic fitness and sprint
      speed during 15 days of 6 degrees head-down bed rest (simulated microgravity).
      Seven male subjects underwent two such bed-rest studies in random order: one as a
      control study (no exercise) and one with daily supine LBNP treadmill exercise.
      After controlled bed-rest, time to exhaustion during an upright treadmill
      exercise test decreased 10%, peak oxygen consumption during the test decreased
      14%, and sprint speed decreased 16% (all P < 0.05). Supine LBNP exercise during
      bed rest maintained all the above variables at pre-bed-rest levels. Our findings
      support further evaluation of LBNP exercise as a countermeasure against long-term
      microgravity-induced deconditioning.

PMID- 10904056
TI  - Mechanical dissociation of bronchi from parenchyma in the immature piglet lung.
AB  - Previous studies of isolated piglet lungs suggested that local distending forces
      around bronchi might be relatively weak before postnatal growth and maturation.
      The present study used tantalum bronchograms to compare pressure-diameter
      relationships of bronchi in situ and after excision from the parenchyma in
      immature (3- to 7-day-old) and mature (3-mo-old) piglets. The mature group
      reproduced behavior that is well established in mature lungs from other species;
      i.e., bronchial diameters maintained a constant relationship to the parenchyma as
      the lungs were deflated from maximum to minimum volume. In sharp contrast,
      diameters failed to change until the immature lungs were deflated to <5 cmH(2)O
      transpulmonary pressure. Total percent change in bronchial diameter was then only
      24% in the immature lungs compared with 47% in the mature lungs (P < 0.002).
      Total elastances of mature generation 3-8 bronchi did not change when they were
      excised from the parenchyma. However, in the same generations of immature
      bronchi, total elastances were lower after than before (1.06 vs. 1.60 cmH(2)O/%,
      P < 0.05) excision from the parenchyma. Elastances of the excised immature and
      mature bronchi were then the same (1.06 vs. 1.03 cmH(2)O/%, not significant).
      Because elastic moduli of the lung parenchyma are also similar in the two age
      groups, it was concluded that local features of airway-parenchyma coupling
      limited the generation of local parenchymal recoil around bronchi in the immature
      lungs.

PMID- 10904057
TI  - Effects of crocetin on pulmonary gas exchange in foxhounds during hypoxic
      exercise.
AB  - The carotenoid compound crocetin has been hypothesized to enhance the diffusion
      of O(2) through plasma, and observations in the rat and rabbit have revealed
      improvement in arterial PO(2) when crocetin is given. To determine whether
      crocetin enhances diffusion of O(2) between alveolar gas and the red blood cell
      in the pulmonary capillary in vivo, five foxhounds, two previously subjected to
      sham and three to actual lobectomy or pneumonectomy, were studied while breathing
      14% O(2) at rest and during moderate and heavy exercise before and within 10 min
      after injection of a single dose of crocetin as the trans isomer of sodium
      crocetinate (TSC) at 100 microg/kg iv. This dose is equivalent to that used in
      previous studies and would yield an initial plasma concentration of 0.7-1.0
      microg/ml. Ventilation-perfusion inequality and pulmonary diffusion limitation
      were assessed by the multiple inert gas elimination technique in concert with
      conventional measurements of arterial and mixed venous O(2) and CO(2). TSC had no
      effect on ventilation, cardiac output, O(2) consumption, arterial
      PO(2)/saturation, or pulmonary O(2) diffusing capacity. There were minor
      reductions in ventilation-perfusion mismatching (logarithm of the standard
      deviation of perfusion fell from 0.48 to 0.43, P = 0.001) and in CO(2) output and
      respiratory exchange ratio (P = 0.05), which may have been due to TSC or to
      persisting effects of the first exercise bout. Spectrophotometry revealed that
      TSC disappeared from plasma with a half time of approximately 10 min. We conclude
      that, in this model of extensive pulmonary O(2) diffusion limitation, TSC as
      given has no effect on O(2) exchange or transport. Whether the original
      hypothesis is invalid, the dose of TSC was too low, or plasma diffusion of O(2)
      is not rate limiting without TSC cannot be discerned from the present study.

PMID- 10904058
TI  - Role of core temperature as a stimulus for cold acclimation during repeated
      immersion in 20 degrees C water.
AB  - The relative importance of skin vs. core temperature for stimulating cold
      acclimation (CA) was examined by 5 wk of daily 1-h water immersions (20 degrees
      C) in resting (RG) and exercising (EG) subjects. Rectal temperature fell (0.8
      degrees C; P < 0.05) during immersion only in RG. Skin temperature fell (P <
      0.05) similarly in both groups. Physiological responses during cold-air exposure
      (90 min, 5 degrees C) were assessed before and after CA. Body temperatures and
      metabolic heat production were similar in both groups with no change due to CA.
      Cardiac output was lower (P < 0.05) in both groups post-CA (10.4 +/- 1.2 l/min)
      than pre-CA (12.2 +/- 1. 0 l/min), but mean arterial pressure was unchanged (pre
      CA 107 +/- 2 mmHg, post-CA 101 +/- 2 mmHg). The increase in norepinephrine was
      greater (P < 0.05) post-CA (954 +/- 358 pg/ml) compared with pre-CA (1,577 +/-
      716 pg/ml) for RG, but CA had no effect on the increase in norepinephrine for EG
      (pre-CA 1,288 +/- 438 pg/ml, post-CA 1,074 +/- 279 pg/ml). Skin temperature
      reduction alone may be a sufficient stimulus during CA for increased
      vasoconstrictor response, but core temperature reduction appears necessary to
      enhance sympathetic activation during cold exposure.

PMID- 10904059
TI  - Sexually dimorphic expression of myosin heavy chains in the adult mouse masseter.
AB  - Little is known regarding the role of androgenic hormones in the maintenance of
      myosin heavy chain (MHC) composition of rodent masticatory muscles. Because the
      masseter is the principal jaw closer in rodents, we felt it was important to
      characterize the influence of androgenic hormones on the MHC composition of the
      masseter. To determine the extent of sexual dimorphism in the phenotype of
      masseter muscle fibers of adult (10-mo-old) C57 mice, we stained tissue sections
      with antibodies specific to type IIa and IIb MHC isoforms. Females contain twice
      as many fibers containing the IIa MHC as males, and males contain twice as many
      fibers containing the IIb MHC as females. There is a modest amount of
      regionalization of MHC phenotypes in the mouse masseter. The rostral portions of
      the masseter are composed mostly of type IIa fibers, whereas the midsuperficial
      and caudal regions contain mostly type IIb fibers. Using immunoblots, we showed
      that castration results in an increase in the expression of type IIa MHC fibers
      in males. Ovariectomy has no effect on the fiber type composition in females. We
      conclude that testosterone plays a role in the maintenance of MHC expression in
      the adult male mouse masseter.

PMID- 10904060
TI  - Age-dependent core temperature responses of conscious rabbits to acute hypoxemia.
AB  - Experiments were carried out on chronically instrumented newborn and older
      rabbits to characterize their core temperature (T(c)) responses to acute
      hypoxemia and to differentiate "forced" vs. "regulated" thermoregulatory
      responses. Three age ranges of kits were studied: 4-6, 9-11, and 28-30 days of
      age. During an experiment, T(c), selected ambient temperature (T(a)), and oxygen
      consumption were measured from kits studied in a thermocline during a control
      period of normoxemia, an experimental period of normoxemia or hypoxemia (fraction
      of inspired oxygen 0.10), and a recovery period of normoxemia. We reasoned that
      no change or a decrease in T(a) while T(c) decreased during hypoxemia would
      indicate a regulated thermoregulatory response, whereas an increase in T(a) while
      T(c) decreased during hypoxemia would indicate a forced thermoregulatory
      response. T(c) decreased during acute hypoxemia in the older kits but not in the
      4- to 6-day-old kits; the decrease in T(c) was accentuated on postnatal days 28
      30 compared with postnatal days 9-11. T(a) decreased or stayed the same during
      exposure to acute hypoxemia. Our data provide evidence that postnatal maturation
      influences the T(c) response of rabbits to acute hypoxemia and that the decrease
      in T(c) during hypoxemia in the older kits results from a regulated
      thermoregulatory response.

PMID- 10904061
TI  - Acute vs. chronic effects of elevated hemoglobin O(2) affinity on O(2) transport
      in maximal exercise.
AB  - These studies were conducted to compare the effects on systemic O(2) transport of
      chronically vs. acutely increased Hb O(2) affinity. O(2) transport during maximal
      normoxic and hypoxic [inspired PO(2) (PI(O(2))) = 70 and 55 Torr, respectively]
      exercise was studied in rats with Hb O(2) affinity that was increased chronically
      by sodium cyanate (group 1) or acutely by transfusion with blood obtained from
      cyanate-treated rats (group 2). Group 3 consisted of normal rats. Hb O(2) half
      saturation pressure (P(50); Torr) during maximal exercise was approximately 26 in
      groups 1 and 2 and approximately 46 in group 3. In normoxia, maximal blood O(2)
      convection (TO(2 max) = cardiac output x arterial blood O(2) content) was similar
      in all groups, whereas in hypoxia TO(2 max) was significantly higher in groups 1
      and 2 than in group 3. Tissue O(2) extraction (arteriovenous O(2)
      content/arterial O(2) content) was lowest in group 1, intermediate in group 2,
      and highest in group 3 (P < 0.05) at all exercise PI(O(2)) values. In normoxia,
      maximal O(2) utilization (VO(2 max)) paralleled O(2) extraction ratio and was
      lowest in group 1, intermediate in group 2, and highest in group 3 (P < 0.05). In
      hypoxia, the lower O(2) extraction ratio values of groups 1 and 2 were offset by
      their higher TO(2 max); accordingly, their differences in VO(2 max) from group 3
      were attenuated or reversed. Tissue O(2) transfer capacity (VO(2 max)/mixed
      venous PO(2)) was lowest in group 1 and comparable in groups 2 and 3. We conclude
      that lowering Hb P(50) has opposing effects on TO(2 max) and O(2) extraction
      ratio, with the relative magnitude of these changes, which varies with PI(O(2)),
      determining VO(2 max). Although the lower O(2) extraction ratio of groups 2 vs. 3
      suggests a decrease in tissue PO(2) diffusion gradient secondary to the low
      P(50), the lower O(2) extraction ratio of groups 1 vs. 2 suggests additional
      negative effects of sodium cyanate and/or chronically low Hb P(50) on tissue O(2)
      transfer.

PMID- 10904062
TI  - Centrally administered MTII affects feeding, drinking, temperature, and activity
      in the Sprague-Dawley rat.
AB  - MTII, an agonist of melanocortinergic receptors, is a well-documented
      anorexigenic agent in rats. Many investigators have reported its effects on
      feeding without considering concurrent alterations in other behaviors.
      Accordingly, we performed studies to simultaneously measure nocturnal feeding,
      drinking, activity, and temperature of rats after intracerebroventricular (third
      ventricle) administration of a wide dose range of MTII (0.05-500 ng). We observed
      that MTII modulates these physiological parameters in a dose-dependent manner.
      Low doses of MTII (0.05 ng) caused reductions in feeding without alterations in
      body temperature, drinking, or activity. In contrast, hyperthermia and disrupted
      drinking patterns, along with food intake reductions, were evident at doses
      exceeding 50 ng. The fact that low doses altered only feeding, whereas higher
      doses affected a range of parameters, suggests that certain melanocortin-induced
      behavioral changes may be mediated by distinct populations of melanocortin
      receptors with varying affinities or that those changes seen at higher doses may
      be nonspecific in nature.

PMID- 10904063
TI  - Peak flowmeter resistance decreases peak expiratory flow in subjects with COPD.
AB  - Previous studies have shown that the added resistance of a mini-Wright peak
      expiratory flow (PEF) meter reduced PEF by approximately 8% in normal subjects
      because of gas compression reducing thoracic gas volume at PEF and thus driving
      elastic recoil pressure. We undertook a body plethysmographic study in 15
      patients with chronic obstructive pulmonary disease (COPD), age 65.9 +/- 6.3 yr
      (mean +/- SD, range 53-75 yr), to examine whether their recorded PEF was also
      limited by the added resistance of a PEF meter. The PEF meter increased alveolar
      pressure at PEF (Ppeak) from 3.7 +/- 1.4 to 4.7 +/- 1.5 kPa (P = 0.01), and PEF
      was reduced from 3.6 +/- 1.3 l/s to 3.2 +/- 0.9 l/s (P = 0.01). The influence of
      flow limitation on PEF and Ppeak was evaluated by a simple four-parameter model
      based on the wave-speed concept. We conclude that added external resistance in
      patients with COPD reduced PEF by the same mechanisms as in healthy subjects.
      Furthermore, the much lower Ppeak in COPD patients is a consequence of more
      severe flow limitation than in healthy subjects and not of deficient muscle
      strength.

PMID- 10904064
TI  - Peripheral chemoreflex function in hyperoxia following ventilatory
      acclimatization to altitude.
AB  - After a period of ventilatory acclimatization to high altitude (VAH), a degree of
      hyperventilation persists after relief of the hypoxic stimulus. This is likely,
      in part, to reflect the altered acid-base status, but it may also arise, in part,
      from the development during VAH of a component of carotid body (CB) activity that
      cannot be entirely suppressed by hyperoxia. To test this hypothesis, eight
      volunteers undergoing a simulated ascent of Mount Everest in a hypobaric chamber
      were acutely exposed to 30 min of hyperoxia at various stages of acclimatization.
      For the second 10 min of this exposure, the subjects were given an infusion of
      the CB inhibitor, dopamine (3 microg. kg(-1). min(-1)). Although there was both a
      significant rise in ventilation (P < 0.001) and a fall in end-tidal PCO(2) (P <
      0.001) with VAH, there was no progressive effect of dopamine infusion on these
      variables with VAH. These results do not support a role for CB in generating the
      persistent hyperventilation that remains in hyperoxia after VAH.

PMID- 10904065
TI  - High-abundance mRNAs in human muscle: comparison between young and old.
AB  - To gain a better understanding of the potential role of altered gene expression
      in the diminished muscle function in old age, we performed a broad search for
      transcripts expressed at quantitatively different levels in younger (21-24 yr)
      and older (66-77 yr) human vastus lateralis muscle by serial analysis of gene
      expression (SAGE). Because SAGE was based on RNA pooled from muscle of several
      different subjects, relative concentrations of selected mRNAs also were
      determined in individual muscle samples by quantitative RT-PCR. There were 702
      SAGE tags detected at least 10 times in one or both mRNA pools, and the detection
      frequency was different (at P < 0.01) between young and older muscle for 89 of
      these. The ratio of myosin heavy chain 2a mRNA to myosin heavy chain 1 mRNA was
      reduced in older muscle. The mRNAs encoding several mitochondrial proteins
      involved in electron transport (including several subunits of cytochrome-c
      oxidase and NADH dehydrogenase) and subunits of ATP synthase were approximately
      30% less abundant in older muscle. Several mRNAs encoding enzymes involved in
      glucose metabolism also were less abundant in older muscle. Analysis of
      individual samples revealed that the differences suggested by SAGE were not
      artifacts of atypical gene expression in one or a few individuals. These data
      suggest that some of the phenotypic changes in senescent muscle may be related to
      altered gene transcription.

PMID- 10904067
TI  - Ventricular motion during the ejection phase: a computational analysis.
AB  - In the present paper, the study of the ventricular motion during systole was
      addressed by means of a computational model of ventricular ejection. In
      particular, the implications of ventricular motion on blood acceleration and
      velocity measurements at the valvular plane (VP) were evaluated. An algorithm was
      developed to assess the force exchange between the ventricle and the surrounding
      tissue, i.e., the inflow and outflow vessels of the heart. The algorithm, based
      on the momentum equation for a transitory flowing system, was used in a fluid
      structure model of the ventricle that includes the contractile behavior of the
      fibers and the viscous and inertial forces of the intraventricular fluid. The
      model calculates the ventricular center of mass motion, the VP motion, and
      intraventricular pressure gradients. Results indicate that the motion of the
      ventricle affects the noninvasive estimation of the transvalvular pressure
      gradient using Doppler ultrasound. The VP motion can lead to an underestimation
      equal to 12.4 +/- 6.6%.

PMID- 10904066
TI  - Supraspinal fatigue during intermittent maximal voluntary contractions of the
      human elbow flexors.
AB  - Responses to transcranial magnetic stimulation in human subjects (n = 9) were
      studied during series of intermittent isometric maximal voluntary contractions
      (MVCs) of the elbow. Stimuli were given during MVCs in four fatigue protocols
      with different duty cycles. As maximal voluntary torque fell during each
      protocol, the torque increment evoked by cortical stimulation increased from
      approximately 1.5 to 7% of ongoing torque. Thus "supraspinal" fatigue developed
      in each protocol. The motor evoked potential (MEP) and silent period in the elbow
      flexor muscles also changed. The silent period lengthened by 20-75 ms (lowest to
      highest duty cycle protocol) and recovered significantly with a 5-s rest. The MEP
      increased in area by >50% in all protocols and recovered significantly with 10 s,
      but not 5 s, of rest. These changes are similar to those during sustained MVC.
      The central fatigue demonstrated by the torque increments evoked by the stimuli
      did not parallel the changes in the electromyogram responses. This suggests that
      part of the fatigue developed during intermittent exercise is "upstream" of the
      motor cortex.

PMID- 10904068
TI  - Detailed flow patterns in the nasal cavity.
AB  - The human nasal cavity filters and conditions inspired air while providing
      olfactory function. Detailed experimental study of nasal airflow patterns has
      been limited because of the complex geometry of the nasal cavity. In this work,
      particle image velocimetry was used to determine two-dimensional instantaneous
      velocity vector fields in parallel planes throughout a model of the nasal cavity
      that was subjected to a nonoscillatory flow rate of 125 ml/s. The model, which
      was fabricated from 26 computed tomography scans by using rapid prototyping
      techniques, is a scaled replica of a human right nasal cavity. The resulting
      vector plots show that the flow is laminar and regions of highest velocity are in
      the nasal valve and in the inferior airway. The relatively low flow in the
      olfactory region appears to protect the olfactory bulb from particulate
      pollutants. Low flows were also observed in the nasal meatuses, whose primary
      function has been the subject of debate. Comparison of sequentially recorded data
      suggests a steady flow.

PMID- 10904069
TI  - Upregulation of NOS by simulated microgravity, potential cause of orthostatic
      intolerance.
AB  - Prolonged exposure to microgravity during spaceflight or extended bed rest
      results in cardiovascular deconditioning, marked by orthostatic intolerance and
      hyporesponsiveness to vasopressors. Earlier studies primarily explored fluid and
      electrolyte balance and baroreceptor and vasopressor systems in search of a
      possible mechanism. Given the potent vasodilatory and natriuretic actions of
      nitric oxide (NO), we hypothesized that cardiovascular adaptation to microgravity
      may involve upregulation of the NO system. Male Wistar rats were randomly
      assigned to a control group or a group subjected to simulated microgravity by
      hindlimb unloading (HU) for 20 days. Tissues were harvested after death for
      determination of total nitrate and nitrite (NOx) as well as endothelial (e),
      inducible (i), and neuronal (n) NO synthase (NOS) proteins by Western blot.
      Separate subgroups were used to test blood pressure response to norepinephrine
      and the iNOS inhibitor aminoguanidine. Compared with controls, the HU group
      showed a significant increase in tissue NOx content and an upregulation of iNOS
      protein abundance in thoracic aorta, heart, and kidney and of nNOS protein
      expression in the brain and kidney but no discernible change in eNOS expression.
      This was associated with marked attenuation of hypertensive response to
      norepinephrine and a significant increase in hypertensive response to
      aminoguanidine, suggesting enhanced iNOS-derived NO generation in the HU group.
      Upregulation of these NOS isotypes can contribute to cardiovascular adaptation to
      microgravity by promoting vasodilatory tone and natriuresis and depressing
      central sympathetic outflow. If true in humans, short-term administration of an
      iNOS inhibitor may ameliorate orthostatic intolerance in returning astronauts and
      patients after extended bed rest.

PMID- 10904070
TI  - Measurement of fat mass using DEXA: a validation study in elderly adults.
AB  - The accuracy of total body fat mass and leg fat mass measurements by fan-beam
      dual-energy X-ray absorptiometry (DEXA) was assessed in 60 healthy elderly
      subjects (aged 70-79 yr). Total fat and leg fat mass at four leg regions (total
      leg, thigh, midthigh, and calf) were measured with the QDR 4500A (Hologic,
      Waltham, MA). The four-compartment model and multislice computed tomography scans
      were selected as criterion methods for total fat and leg fat mass, respectively.
      Total fat mass from DEXA was positively associated with fat mass from the four
      compartment model with a standard error of the estimate ranging from 1.4 to 1.6
      kg. DEXA fan-beam tended to overestimate fat mass for total leg and total thigh
      fat mass, whereas only marginal differences in fat mass measurements at the
      midthigh and calf were demonstrated (</=0.08 kg, P < 0.0005). Although there were
      significant differences between DEXA fan beam and the criterion methods, these
      differences were of small magnitude, suggesting that DEXA is an accurate method
      for measurement of fat mass for the elderly.

PMID- 10904071
TI  - Analysis of responses of garlic derivatives in the pulmonary vascular bed of the
      rat.
AB  - Allicin, an extract from garlic, has been shown to be a systemic and pulmonary
      arterial vasodilator that acts by an unknown mechanism. In the present
      experiments, pulmonary vascular responses to allicin (10-100 microg), allyl
      mercaptan (0.3-1 mg), and diallyl disulfide (0.3-1 mg) were studied in the
      isolated lung of the rat under constant-flow conditions. When baseline tone in
      the pulmonary vascular bed of the rat was raised to a high-steady level with the
      thromboxane A(2) mimic U-46619, dose-related decreases in pulmonary arterial
      pressure were observed. In terms of the mechanism of action of allicin
      vasodilator activity in the rat, responses to allicin were not significantly
      different after administration of the nitric oxide synthase inhibitor N(omega)
      nitro-L-arginine methyl ester, the K(ATP)(+) channel antagonist U-37883A, or the
      cyclooxygenase inhibitor sodium meclofenamate, or when lung ventilation was
      interrupted. These data show that allicin has significant vasodilator activity in
      the pulmonary vascular bed of the rat, whereas allyl mercaptan and diallyl
      disulfide produced no significant changes in pulmonary arterial perfusion
      pressure. The present data suggest that pulmonary vasodilator responses to
      allicin are independent of the synthesis of nitric oxide, ATP-sensitive K(+)
      channels, activation of cyclooxygenase enzyme, or changes in bronchomotor tone in
      the pulmonary vascular bed of the rat.

PMID- 10904072
TI  - Changes of interstitial fluid volume in superficial tissues detected by a
      miniature ultrasound device.
AB  - We evaluated the changes of tissue layer thickness in circumscribed superficial
      tissue areas with a 10-MHz A-mode and a 20-MHz B-mode ultrasound device under
      alterations in body posture and plasma volume to detect fluid shifts between the
      different compartments. In 20 male volunteers, we measured tissue thickness by A
      mode and corium and subcutis thickness by B mode at the forehead before and 30
      min after three procedures: change from upright to supine position (P1); change
      from upright to 30 degrees head-down-tilt position (P2); infusion of 10 ml/kg
      body wt of Ringer solution (P3). We found a significant correlation between
      baseline tissue thickness and the sum of corium and subcutis thicknesses (r =
      0.75, P < 0.01). The changes of body posture and plasma volume resulted in
      significant increases of tissue thickness (P1, 2.9%; P2, 11.6%; P3, 5.8%) and
      corium thickness (P1, 4.7%; P2, 8.1%; P3, 9.1%) but not of the sum of chorium and
      subcutis thicknesses. We conclude that fluid shifts from the intravascular to the
      extravascular compartment are detectable by evaluating corium thickness with a B
      mode, or more easily tissue thickness with an A-mode, ultrasound device.

PMID- 10904073
TI  - Detecting lung overdistention in newborns treated with high-frequency oscillatory
      ventilation.
AB  - Positive airway pressure (Paw) during high-frequency oscillatory ventilation
      (HFOV) increases lung volume and can lead to lung overdistention with potentially
      serious adverse effects. To date, no method is available to monitor changes in
      lung volume (DeltaVL) in HFOV-treated infants to avoid overdistention. In five
      newborn piglets (6-15 days old, 2.2-4.2 kg), we investigated the use of direct
      current-coupled respiratory inductive plethysmography (RIP) for this purpose by
      evaluating it against whole body plethysmography. Animals were instrumented,
      fitted with RIP bands, paralyzed, sedated, and placed in the plethysmograph. RIP
      and plethysmography were simultaneously calibrated, and HFOV was instituted at
      varying Paw settings before (6-14 cmH(2)O) and after (10-24 cmH(2)O) repeated
      warm saline lung lavage to induce experimental surfactant deficiency. Estimates
      of Delta VL from both methods were in good agreement, both transiently and in the
      steady state. Maximal changes in lung volume (Delta VL(max)) from all piglets
      were highly correlated with Delta VL measured by RIP (in ml) = 1.01 x changes
      measured by whole body plethysmography - 0.35; r(2) = 0.95. Accuracy of RIP was
      unchanged after lavage. Effective respiratory system compliance (Ceff) decreased
      after lavage, yet it exhibited similar sigmoidal dependence on Delta VL(max) pre-
      and postlavage. A decrease in Ceff (relative to the previous Paw setting) as
      Delta VL(max) was methodically increased from low to high Paw provided a
      quantitative method for detecting lung overdistention. We conclude that RIP
      offers a noninvasive and clinically applicable method for accurately estimating
      lung recruitment during HFOV. Consequently, RIP allows the detection of lung
      overdistention and selection of optimal HFOV from derived Ceff data.

PMID- 10904074
TI  - System of automated gas-exchange analysis for the investigation of metabolic
      processes.
AB  - Conventional gas-exchange instruments are confined to the measurement of O(2)
      consumption (VO(2)) and CO(2) production (VCO(2)) and are subject to a variety of
      errors. This handicaps the performance of these devices at inspired O(2) fraction
      (FI(O(2))) > 0.40 and limits their applicability to indirect calorimetry only. We
      describe a device based on the automation of the Douglas bag technique that is
      capable of making continuous gas-exchange measurements of multiple species over a
      broad range of experimental conditions. This system is validated by using a
      quantitative methanol-burning lung model modified to provide reproducible
      (13)CO(2) production. The average error for VO(2) and VCO(2) over the FI(O(2))
      range of 0.21-0.8. is 2.4 and 0.8%, respectively. The instrument is capable of
      determining the differential atom% volume of known references of (13)CO(2) to
      within 3.4%. This device reduces the sources of error that thwart other
      instruments at FI(O(2)) > 0. 40 and demonstrates the capacity to explore other
      expressions of metabolic activity in exhaled gases related to the excretion of
      (13)CO(2).

PMID- 10904075
TI  - Physiology in microgravity.
AB  - Studies of physiology in microgravity are remarkably recent, with almost all the
      data being obtained in the past 40 years. The first human spaceflight did not
      take place until 1961. Physiological measurements in connection with the early
      flights were crude, but, in the past 10 years, an enormous amount of new
      information has been obtained from experiments on Spacelab. The United States and
      Soviet/Russian programs have pursued different routes. The US has mainly
      concentrated on relatively short flights but with highly sophisticated equipment
      such as is available in Spacelab. In contrast, the Soviet/Russian program
      concentrated on first the Salyut and then the Mir space stations. These had the
      advantage of providing information about long-term exposure to microgravity, but
      the degree of sophistication of the measurements in space was less. It is hoped
      that the International Space Station will combine the best of both approaches.
      The most important physiological changes caused by microgravity include bone
      demineralization, skeletal muscle atrophy, vestibular problems causing space
      motion sickness, cardiovascular problems resulting in postflight orthostatic
      intolerance, and reductions in plasma volume and red cell mass. Pulmonary
      function is greatly altered but apparently not seriously impaired. Space
      exploration is a new frontier with long-term missions to the moon and Mars not
      far away. Understanding the physiological changes caused by long-duration
      microgravity remains a daunting challenge.

PMID- 10904076
TI  - Microgravity and the lung.
AB  - Although environmental physiologists are readily able to alter many aspects of
      the environment, it is not possible to remove the effects of gravity on Earth.
      During the past decade, a series of space flights were conducted in which
      comprehensive studies of the lung in microgravity (weightlessness) were
      performed. Stroke volume increases on initial exposure to microgravity and then
      decreases as circulating blood volume is reduced. Diffusing capacity increases
      markedly, due to increases in both pulmonary capillary blood volume and membrane
      diffusing capacity, likely due to more uniform pulmonary perfusion. Both
      ventilation and perfusion become more uniform throughout the lung, although much
      residual inhomogeneity remains. Despite the improvement in the distribution of
      both ventilation and perfusion, the range of the ventilation-to-perfusion ratio
      seen during a normal breath remains unaltered, possibly because of a spatial
      mismatch between ventilation and perfusion on a small scale. There are unexpected
      changes in the mixing of gas in the periphery of the lung, and evidence suggests
      that the intrinsic inhomogeneity of the lung exists at a scale of an acinus or a
      few acini. In addition, aerosol deposition in the alveolar region is unexpectedly
      high compared with existing models.

PMID- 10904077
TI  - Effects of fiber composition and hindlimb unloading on the vasodilator properties
      of skeletal muscle arterioles.
AB  - It has been hypothesized that microgravity-induced orthostatic hypotension may
      result from an exaggerated vasodilatory responsiveness of arteries. The purpose
      of this study was to determine whether skeletal muscle arterioles exhibit
      enhanced vasodilation in rats after 2 wk of hindlimb unloading (HU). First-order
      arterioles isolated from soleus and white gastrocnemius muscles were tested in
      vitro for vasodilatory responses to isoproterenol (Iso), adenosine (Ado), and
      sodium nitroprusside (SNP). HU had no effect on responses induced by Iso but
      diminished maximal vasodilation to Ado and SNP in both muscles. In addition,
      vasodilatory responses in arterioles from control rats varied between muscle
      types. Maximal dilations induced by Iso (soleus: 42 +/- 6%; white gastrocnemius:
      60 +/- 7%) and Ado (soleus: 51 +/- 8%; white gastrocnemius: 81 +/- 6%) were
      greater in arterioles from white gastrocnemius muscles. These data do not support
      the hypothesis that microgravity-induced orthostatic hypotension results from an
      enhanced vasodilatory responsiveness of skeletal muscle arterioles. Furthermore,
      the data support the concept that dilatory responsiveness of arterioles varies in
      muscle composed of different fiber types.

PMID- 10904078
TI  - Familial aggregation: sorting susceptibility from shared environment.

PMID- 10904080
TI  - Stat bite: Income of Medicare recipients, 1998.

PMID- 10904079
TI  - Costs studies show clinical trials, standard therapy may be equal.

PMID- 10904081
TI  - Nonhormonal agents show promise against hot flashes.

PMID- 10904082
TI  - Breast self-examination: A mixed message.

PMID- 10904083
TI  - Research seeks links between cancer, gene-environment interactions.

PMID- 10904084
TI  - Canadian government intends to attack smoking graphically.

PMID- 10904085
TI  - Genetic and hormonal risk factors in breast cancer.
AB  - Breast cancer poses a serious public health problem, and it is hoped that
      identification of genetic and environmental factors that contribute to the
      development of breast cancer will enhance prevention efforts. Two breast cancer
      susceptibility genes (BRCA1 and BRCA2) have been identified, and germline
      mutations in these genes are thought to account for between 5% and 10% of all
      breast cancer cases. Current findings suggest that mutations in other highly
      penetrant genes may play an important role in breast cancer susceptibility, and
      studies aimed at the isolation of these genes are under way. In addition, common
      variants in a number of gene classes are thought to act as low-penetrance
      susceptibility alleles, and efforts to identify and characterize these variants
      are under way. This review discusses the genetic components of susceptibility to
      breast cancer from the standpoint of both human genetics and rat models.

PMID- 10904086
TI  - 15-LOX-1: a novel molecular target of nonsteroidal anti-inflammatory drug-induced
      apoptosis in colorectal cancer cells.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) appear to act via
      induction of apoptosis-programmed cell death-as potential colorectal cancer
      chemopreventive agents. NSAIDs can alter the production of different metabolites
      of polyunsaturated fatty acids (linoleic and arachidonic acids) through effects
      on lipoxygenases (LOXs) and cyclooxygenases. 15-LOX-1 is the main enzyme for
      metabolizing colonic linoleic acid to 13-S-hydroxyoctadecadienoic acid (13-S
      HODE), which induces apoptosis. In human colorectal cancers, the expression of
      this enzyme is reduced. NSAIDs can increase 15-LOX enzymatic activity in normal
      leukocytes, but their effects on 15-LOX in neoplastic cells have been unknown. We
      tested the hypothesis that NSAIDs induce apoptosis in colorectal cancer cells by
      increasing the protein expression and enzymatic activity of 15-LOX-1. METHODS: We
      assessed 15-LOX-1 protein expression and enzymatic activity, 13-S-HODE levels,
      and 15-LOX-1 inhibition in association with cellular growth inhibition and
      apoptosis induced by NSAIDs (primarily sulindac and NS-398) in two colorectal
      cancer cell lines (RKO and HT-29). All P values are two-sided. RESULTS: Sulindac
      and NS-398 progressively increased 15-LOX-1 protein expression in RKO cells (at
      24, 48, and 72 hours) in association with subsequent growth inhibition and
      apoptosis. Increased 13-S-HODE levels and the formation of 15
      hydroxyeicosatetraenoic acid on incubation of the cells with the substrate
      arachidonic acid confirmed the enzymatic activity of 15-LOX-1. Inhibition of 15
      LOX-1 in RKO cells by treatment with caffeic acid blocked NS-398-induced 13-S
      HODE production, cellular growth inhibition, and apoptosis (P =. 007, P<.0001,
      and P<.0001, respectively); growth inhibition and apoptosis were restored by
      adding exogenous 13-S-HODE (P<.0001 for each) but not its parent compound,
      linoleic acid (P = 1.0 for each). Similar results occurred with other NSAIDs and
      in HT-29 cells. CONCLUSIONS: These data identify 15-LOX-1 as a novel molecular
      target of NSAIDs for inducing apoptosis in colorectal carcinogenesis.

PMID- 10904087
TI  - Long-term results of a randomized trial comparing breast-conserving therapy with
      mastectomy: European Organization for Research and Treatment of Cancer 10801
      trial.
AB  - BACKGROUND: Breast-conserving therapy (BCT) has been shown to be as effective as
      mastectomy in the treatment of tumors 2 cm or smaller. However, evidence of its
      efficacy, over the long term, in patients with tumors larger than 2 cm is
      limited. From May 1980 to May 1986, the European Organization for Research and
      Treatment of Cancer carried out a randomized, multicenter trial comparing BCT
      with modified radical mastectomy for patients with tumors up to 5 cm. In this
      analysis, we investigated whether the treatments resulted in different overall
      survival, time to distant metastasis, or time to locoregional recurrence.
      METHODS: Of 868 eligible breast cancer patients randomly assigned to the BCT arm
      or to the modified radical mastectomy arm, 80% had a tumor of 2.1-5 cm. BCT
      comprised lumpectomy with an attempted margin of 1 cm of healthy tissue and
      complete axillary clearance, followed by radiotherapy to the breast and a
      supplementary dose to the tumor bed. The median follow-up was 13.4 years. All P
      values are two-sided. RESULTS: At 10 years, there was no difference between the
      two groups in overall survival (66% for the mastectomy patients and 65% for the
      BCT patients; P =.11) or in their distant metastasis-free rates (66% for the
      mastectomy patients and 61% for the BCT patients; P =.24). The rate of
      locoregional recurrence (occurring before or at the same time as distant
      metastasis) at 10 years did show a statistically significant difference (12% of
      the mastectomy and 20% of the BCT patients; P =. 01). CONCLUSIONS: BCT and
      mastectomy demonstrate similar survival rates in a trial in which the great
      majority of the patients had stage II breast cancer.

PMID- 10904088
TI  - Population stratification in epidemiologic studies of common genetic variants and
      cancer: quantification of bias.
AB  - BACKGROUND: Some critics argue that bias from population stratification (the
      mixture of individuals from heterogeneous genetic backgrounds) undermines the
      credibility of epidemiologic studies designed to estimate the association between
      a genotype and the risk of disease. We investigated the degree of bias likely
      from population stratification in U.S. studies of cancer among non-Hispanic
      Caucasians of European origin. METHODS: An expression of the confounding risk
      ratio-the ratio of the effect of the genetic factor on risk of disease with and
      without adjustment for ethnicity-is used to measure the potential relative bias
      from population stratification. We first use empirical data on the frequency of
      the N-acetyltransferase (NAT2) slow acetylation genotype and incidence rates of
      male bladder cancer and female breast cancer in non-Hispanic U.S. Caucasians with
      ancestries from eight European countries to assess the bias in a hypothetical
      population-based U.S. study that does not take ethnicity into consideration.
      Then, we provide theoretical calculations of the bias over a large range of
      allele frequencies and disease rates. RESULTS: Ignoring ethnicity leads to a bias
      of 1% or less in our empirical studies of NAT2. Furthermore, evaluation of a wide
      range of allele frequencies and representative ranges of cancer rates that exist
      across European populations shows that the risk ratio is biased by less than 10%
      in U.S. studies except under extreme conditions. We note that the bias decreases
      as the number of ethnic strata increases. CONCLUSIONS: There will be only a small
      bias from population stratification in a well-designed case-control study of
      genetic factors that ignores ethnicity among non-Hispanic U.S. Caucasians of
      European origin. Further work is needed to estimate the effect of population
      stratification within other populations.

PMID- 10904089
TI  - Familial risk of hepatocellular carcinoma among chronic hepatitis B carriers and
      their relatives.
AB  - BACKGROUND: Familial predisposition as a risk factor for hepatocellular carcinoma
      (HCC) in hepatitis B virus (HBV) carriers has not been thoroughly explored.
      METHODS: The HCC risk associated with having parents and/or siblings with HCC was
      evaluated by use of a cohort study of 4808 male HBV carriers. A case-control
      family study was also conducted on data from first-degree relatives of 553 HBV
      carriers who had newly diagnosed HCC (case subjects) and 4684 HBV carriers
      without HCC (control subjects). RESULTS: In the cohort study, HBV carriers with a
      family history of HCC had a multivariate-adjusted rate ratio for HCC of 2.41 (95%
      confidence interval [CI] = 1.47-3.95) compared with HBV carriers without a family
      history of HCC. For carriers with two or more affected relatives, the ratio
      increased to 5.55 (95% CI = 2.02-15.26). Cumulative HCC risk by age 70 years was
      235.6 per 1000 (95% CI = 95. 3-375.9 per 1000) for HBV carriers with family
      history compared with 88.9 per 1000 (95% CI = 67.9-109.9 per 1000) for those
      without. In the case-control family study, first-degree relatives of case
      subjects were more likely to have HCC (age-sex-adjusted odds ratio [OR] = 2.57;
      95% CI = 2.03-3.25) than first-degree relatives of control subjects. The excess
      risk of HCC among relatives was particularly evident in siblings (sisters-age
      adjusted OR = 4.55 [95% CI = 2.22-9.31]; brothers-age-adjusted OR = 3.73 [95% CI
      = 2. 64-5.27]), but it was also observed in parents. The cumulative risk of HCC
      to age 80 years was 83.0 per 1000 among relatives of case subjects and 42.0 per
      1000 among relatives of control subjects. Among relatives of case subjects, the
      cumulative risk of HCC was greater if the case subjects were diagnosed before age
      50 years (two-sided P =.047). Liver cirrhosis was 2.29 (95% CI = 1.68-3.11) times
      more frequent in relatives of case subjects than in relatives of control
      subjects. CONCLUSIONS: First-degree relatives of patients with HBV-related HCC
      appear to be at increased risk of HCC and should be considered in the formulation
      of HCC-screening programs.

PMID- 10904090
TI  - Treatment-associated leukemia following testicular cancer.
AB  - BACKGROUND: Men with testicular cancer are at an increased risk of leukemia, but
      the relationship to prior treatments is not well characterized. The purpose of
      our study was to describe the risk of leukemia following radiotherapy and
      chemotherapy for testicular cancer. METHODS: Within a population-based cohort of
      18 567 patients diagnosed with testicular cancer (from 1970 through 1993), a case
      control study of leukemia was undertaken. Radiation dose to active bone marrow
      and type and cumulative amount of cytotoxic drugs were compared between 36 men
      who developed leukemia and 106 matched control patients without leukemia.
      Conditional logistic regression was used to estimate the relative risk of
      leukemia associated with specific treatments. All P values are two-sided.
      RESULTS: Radiotherapy (mean dose to active bone marrow, 12.6 Gy) without
      chemotherapy was associated with a threefold elevated risk of leukemia. Risk
      increased with increasing dose of radiation to active bone marrow (P for trend
      =.02), with patients receiving radiotherapy to the chest as well as to the
      abdominal/pelvic fields accounting for much of the risk at higher doses.
      Radiation dose to active bone marrow and the cumulative dose of cisplatin (P for
      trend =.001) were both predictive of excess leukemia risk in a model adjusted for
      all treatment variables. The estimated relative risk of leukemia at a cumulative
      dose of 650 mg cisplatin, which is commonly administered in current testicular
      cancer treatment regimens, was 3.2 (95% confidence interval = 1.5-8.4); larger
      doses (1000 mg) were linked with statistically significant sixfold increased
      risks. CONCLUSIONS: Past treatments for testicular cancer are associated with an
      increased risk of leukemia, with evidence for dose-response relationships for
      both radiotherapy and cisplatin-based chemotherapy. Statistically nonsignificant
      excesses are estimated for current radiotherapy regimens limited to the abdomen
      and pelvis: Among 10 000 patients given a treatment dose of 25 Gy and followed
      for 15 years, an excess of nine leukemias is predicted; cisplatin-based
      chemotherapy (dose, 650 mg) might result in 16 cases of leukemia. The survival
      advantage provided by current radiotherapy and chemotherapy regimens for
      testicular cancer far exceeds the small absolute risk of leukemia.

PMID- 10904091
TI  - Multiple births and risk of epithelial ovarian cancer.
AB  - BACKGROUND AND METHODS: Prevailing hypotheses about the causes of ovarian
      carcinogenesis predict that women with a history of multiple births (twins,
      triplets, etc.) should be at increased risk of epithelial ovarian cancer.
      However, the scant available evidence suggests that they may actually be at lower
      risk. To resolve this issue, we pooled data from eight studies involving 2859
      parous women with epithelial ovarian cancer (case patients) and 7434 parous women
      without ovarian cancer (control women). In addition to assessing their history of
      multiple births (and the sex of the children, where available), we obtained
      information on age, parity, oral contraceptive use, and other reproductive
      factors for each woman. Details of tumor histology were available for all case
      patients. We estimated the relative risks of various histologic types of ovarian
      cancers associated with multiple births by using multivariable logistic
      regression analysis, adjusting for matching and confounding variables. RESULTS:
      Among these parous women, 73 case patients (2. 6%) and 257 control women (3.5%)
      had a history of multiple births. The adjusted summary odds ratio (OR) for
      developing all types of epithelial ovarian cancer that are associated with
      multiple births was 0.81 (95% confidence interval [CI] = 0.61-1.08). We found no
      evidence that risks associated with multiple births differed among women with
      borderline or invasive tumors and among women with same-sex and opposite-sex
      offspring from multiple births. The risk reductions appeared specific for
      nonmucinous tumors (n = 2453; summary adjusted OR = 0.71 [95% CI = 0.52-0.98]);
      in contrast, associations with mucinous tumors (n = 406) were heterogeneous
      across studies. CONCLUSIONS: Parous women with nonmucinous ovarian cancer are no
      more likely to have a history of multiple births than other parous women, counter
      to the predictions of current hypotheses for causes of ovarian cancer.

PMID- 10904092
TI  - Lifetime cigarette smoking and colorectal cancer incidence in the Physicians'
      Health Study I.

PMID- 10904093
TI  - Re: clonal expansion and loss of heterozygosity at chromosomes 9p and 17p in
      premalignant esophageal (Barrett's) tissue.

PMID- 10904094
TI  - RESPONSE: re: clonal expansion and loss of heterozygosity at chromosomes 9p and
      17p in premalignant esophageal (Barrett's) tissue

PMID- 10904095
TI  - More about: effect of hormone replacement therapy on breast cancer risk: estrogen
      versus estrogen plus progestin.

PMID- 10904096
TI  - Re: preclinical and clinical development of cyclin-dependent kinase modulators.

PMID- 10904097
TI  - RESPONSE: re: preclinical and clinical development of cyclin-dependent kinase
      modulators

PMID- 10904098
TI  - MCF10DCIS.com xenograft model of human comedo ductal carcinoma in situ.

PMID- 10904099
TI  - The blood fibrinolysis/deep-sea analogy: a hypothesis on the cell signals singlet
      oxygen/photons as natural antithrombotics.

PMID- 10904100
TI  - The continuous infusion of recombinant activated factor VIIa (rFVIIa) in patients
      with factor VIII inhibitors activates the coagulation and fibrinolytic systems
      without clinical complications.
AB  - The standard modality of administration of rFVIIa to patients with FVIII and FIX
      inhibitors is the intermittent infusion every 2 to 6 hours. No untoward local or
      systemic effects have been reported; laboratory data of activation of coagulation
      were reported in the presence of coexistent problems (sepsis, septic shock) or
      with high doses. We treated four patients with FVIII inhibitor with rFVIIa
      administered by continuous infusion by a central vein catheter, monitoring the
      signs of systemic activation of the hemostatic system. The F(1+2) prothrombin
      fragments and the D-dimer increased after the bolus, and remained above the
      baseline values throughout the treatment period. These variations observed during
      the infusion period were not accompanied by clinical events.

PMID- 10904101
TI  - Prothrombin G20210A, factor V Leiden, and factor XIII Val34Leu: common mutations
      of blood coagulation factors and deep vein thrombosis in Austria.
AB  - Mutations in the gene for prothrombin (F2 20210A) and factor V (F5 1691A, factor
      V Leiden) are established risk factors for deep venous thrombosis (DVT).
      Recently, a mutation in the gene for factor XIII (F13 100T) leading to a Valine
      Leucine exchange at amino acid position 34 has been reported to be protective
      against DVT. To analyze the role of these mutations for DVT in Austria, we
      analyzed their prevalence in 154 patients with documented DVT and 308 sex- and
      age-matched control subjects. Allele frequencies of F2 20210A, F5 1691A, and F13
      100T were 0.018, 0.039, and 0.274 among controls, and 0.045, 0.120, and 0.211
      among patients, respectively. Odds ratios for DVT associated with F2 20210A, F5
      1691A, and F13 100T alleles were 2.5 (95% CI: 1.1-5.7), 3.4 (95% CI: 1.9-5.8),
      and 0.7 (95% CI: 0.5-1.0). We conclude that F2 20210A, F5 1691A, and F13 100T are
      common mutations in the Austrian population. F2 20210A and F5 1691 increase the
      risk for DVT, whereas F13 100T is associated with a decreased risk for DVT.
      Routinely, analysis of these mutations may help to analyze the individual risk
      for DVT.

PMID- 10904102
TI  - A novel enzyme immunoassay for plasma thrombospondin. Comparison with beta
      thromboglobulin as platelet activation marker in vitro and in vivo.
AB  - A novel enzyme immunoassay for plasma thrombospondin (TSP) based on commercially
      available monoclonal antibodies was established. The following conditions for
      correct collection and preservation of blood samples were required: venipuncture
      directly into a vacutainer containing citrate, theophylline, adenosine and
      dipyridamole, storage on ice, and separation of plasma within 30 minutes.
      Thereafter, the plasma TSP concentration remained constant at room temperature
      and after five times of freezing and thawing. Both inter- and intraassay
      variation coefficients were 5%. The lower detection limit was 20 microg/L. Median
      TSP concentration among 40 healthy blood donors was 43 microg/L, slightly lower
      than previously published. The assay is valid, reliable, and has certain
      advantages compared with previously published methods. TSP and beta
      thromboglobulin (BTG) were then compared as platelet activation and
      biocompatibility markers in vivo: 23 patients undergoing cardiopulmonary bypass
      (CPB); and in vitro: effect of coating polyvinyl chloride with heparin. The
      kinetic patterns of TSP and BTG were markedly different in vivo but virtually
      identical in vitro, explained by different in vivo clearance mechanisms during
      CPB. We conclude that BTG is superior to TSP for evaluation of platelet
      activation during in vivo CPB, whereas TSP and BTG are virtually identical as
      markers in vitro.

PMID- 10904103
TI  - Molecular requirements in the recognition of low-density lipoproteins (LDL) by
      specific platelet membrane receptors.
AB  - We have demonstrated that platelet low-density lipoprotein (LDL) receptors differ
      from classic LDL receptors of nucleated cells. Although positively charged Arg
      and Lys residues of apoprotein B-100 are known to play a key role in LDL
      recognition by classic LDL receptors, there are no conclusive data on platelet
      LDL receptors. This study investigated the molecular requirements of LDL particle
      recognition by platelet LDL receptors. The involvement of lipid and protein
      fractions was determined by displacement studies of the binding of 125I-LDL to
      platelets and fibroblasts (used as a classical LDL receptor model). The role of
      the protein moiety was evaluated by chemically modifying positively charged apoB
      residues (Lys, Arg, and Tyr) via copper-induced oxidation, cyclohexanedione, and
      tetranitromethane, respectively. The involvement of the lipid fraction was
      determined by ligand binding assays using 125I-LDL particles that had previously
      been delipidated and subjected to apoB solubilization. The degree of particle
      modification was analyzed by agarose/acrylamide gel electrophoresis and anion
      exchange chromatography. Modifying the amino acid residues increased particle
      electronegativity in the following order of potency: CHD-LDL>TNM-LDL>ox
      LDL>native LDL. The results obtained by displacement studies in fibroblasts
      suggested that the gain in the LDL negative charge was the most important factor
      in the loss of receptor affinity. The chemical models of protein modification
      used in our study greatly affected LDL binding to the classical fibroblast
      receptor. In contrast, there was very slight difference in the displacement
      capacity on platelet 125I-LDL binding, which suggests that the protein fraction
      does not play a major role in the interaction of LDL with its platelet receptor.
      On the other hand, whereas modifying the lipid moiety did not alter the ability
      of solubilized 125I-apoB to interact with the classical fibroblast LDL receptor,
      platelet LDL receptors were unable to recognize these particles. In conclusion,
      our results confirm that the protein fraction plays a key role in the fibroblast
      LDL-receptor recognition process, whereas the lipid fraction appears to have a
      more relevant role in platelet LDL-receptor recognition.

PMID- 10904104
TI  - Intravenously and topically applied magnesium in the prevention of arterial
      thrombosis.
AB  - Magnesium (Mg) has been shown to reduce platelet aggregation both in vitro and ex
      vivo, and this antiplatelet effect may be advantageous in the prevention of
      arterial thrombosis. Previous animal studies have shown an antithrombotic effect
      of Mg also in vivo, but mainly with higher Mg concentrations ( approximately 3.0
      4.0 mM). The objectives of the present study were to evaluate the antithrombotic
      effect of (1) intravenous Mg at a lower and clinically more relevant
      concentration and (2) topically applied Mg. The study comprised 30 male rats,
      randomly assigned into 3 groups: (1) placebo group, (2) intravenous Mg group, and
      (3) topical Mg group. A thrombogenic lesion was established by making a
      standardised arteriotomy in the right femoral artery. The vessel was
      transilluminated and thrombus formation was visualised dynamically by in vivo
      microscopy and recorded on videotapes. Thrombus area was measured after ended
      experiment by computer-assisted image analysis. Intravenously administered Mg,
      elevating the S-Mg level to 2.2 mmol/L, significantly reduced the mean thrombus
      area (p<0.05) compared to the control group. Topically applied Mg significantly
      decreased the maximum thrombus area, without any increase in S-Mg level (p<0.05).
      The Mg-treated groups showed no increase in bleeding complications. A transient
      fall in blood pressure was seen in the systemic Mg group, but blood pressures
      were not significantly different between any of the groups at the end of the
      experiment. In conclusion, topically as well as intravenously infused Mg reduce
      arterial thrombus formation in this in vivo rat model without compromising
      haemostasis.

PMID- 10904106
TI  - Asp41-His48 region of streptokinase is important in binding to a substrate
      plasminogen.
AB  - Streptokinase is a plasminogen activator protein produced by several strains of
      beta-hemolytic streptococci. Random mutagenesis of streptokinase was carried out
      for the determination of critical amino acid residues in plasminogen activation.
      We selected and sequenced 14 streptokinase mutants with no plasminogen activation
      activity on skim milk-plasminogen overlay plate. Specific activities of the
      selected streptokinase mutants were determined with chromogenic assay. Eight
      mutants (V19F, V35E, E85D, L292R, D325P, D341E, I345N, and M369L) resulted in
      greatly decreased amidolytic activities. However, unexpectedly, six mutants
      (D41C, S44K, S44P, R45P, H48T, and D220G) showed substantial amidolytic
      activities comparable to that of wild type. Moreover, five-point mutations were
      concentrated on the Asp41-His48 region. These data indicate that the Asp41-His48
      region in a streptokinase-plasminogen binary complex plays an important role in
      binding to a substrate plasminogen.

PMID- 10904105
TI  - Elevation of soluble thrombomodulin antigen levels in the serum and urine of
      streptozotocin-induced diabetes model rats.
AB  - The present study was designed to evaluate the serum thrombomodulin (TM) antigen
      levels, the TM content in several tissues, and vascular endothelium injury in a
      streptozotocin-induced diabetic mellitus model of rats with the basic
      observations concerning soluble serum TM antigen. The soluble TM antigen levels
      in the serum of 1-week-old Sprague-Dawley rats were 1028.7+/-56.8 ng/mL in the
      immunoassay using rabbit anti-rat TM IgG. The levels gradually decreased to about
      400 ng/mL within 11 weeks during the development, and the levels in 11-week-old
      rats were preserved up to 31 weeks of age (experimental period). Identical
      patterns of five kinds of TM antigen subspecies (105, 52, 46, 31, and 28 kDa) in
      the serum were observed during normal development from 1 to 31 weeks in the
      Western blotting under reducing conditions. Soluble TM antigen levels in the
      serum and urine of the model rats were significantly increased to 1. 3 times the
      levels in the buffer-administrated control rats without an increase in the serum
      creatinine levels. In contrast to the TM antigen levels in the serum and urine,
      the TM content in several tissues including the lung, pancreas, kidney, and
      spleen of the model rats significantly decreased by 47% to 10% of those in the
      buffer-administrated control rats. Flattening of the longitudinal ridges in the
      endothelium, crevasse-like endothelial sloughing, platelet activation and
      aggregation, and/or leukocyte adherence on the endothelium were observed in the
      aorta of the model rats based on scanning electron microscopic observations,
      indicating endothelium injury. The present results indicate that the serum TM
      antigen levels increased with injury to the endothelium in the model, even when
      renal dysfunction was not present. It is suggested that increased TM antigen
      levels in diabetic patients could reflect endothelium injury as observed in this
      diabetic model experiment.

PMID- 10904107
TI  - The effects of polysulfonate derivative (GL 2021) on coagulation in vitro and
      thrombosis in vivo.

PMID- 10904108
TI  - Preface

PMID- 10904109
TI  - Introduction

PMID- 10904110
TI  - Functional domains, structural variations and pathogen interactions of MCP, DAF
      and CR1.
AB  - The Regulators of Complement Activation (RCA) are a fascinating group of proteins
      that play important roles in innate and acquired immunity. In this review, we
      examine structure-function aspects of three membrane-bound RCA proteins and
      discuss the unique impact of their genetic organization on their evolution.

PMID- 10904111
TI  - Immunomodulatory functions of murine CR1/2.
AB  - C3-fragments generated upon complement activation play an important role in the
      formation and regulation of immune responses. Receptors interacting with various
      activation fragments of this versatile complement component are expressed on a
      wide variety of cell types, such as lymphocytes, macrophages, dendritic cells,
      follicular dendritic cells, granulocytes, erythrocytes, consequently C3-products
      may influence several biological functions at different sites of the body, where
      complement activation takes place. In the last decade, genes, protein structure
      and functions played by murine complement receptors CR1 and CR2 (mCR1/2) have
      been deciphered. In this review, we wish to relate these properties, and fit it
      into the context of events following in vivo complement activation. We separately
      address the roles played by murine mCR1/2 as BCR coreceptor and as BCR
      independent structure, and propose a mchanism for the utilization of antigen-C3d
      conjugates bound on B cells. Finally, we raise some of the questions that remain
      to be elucidated in order to get a more precise picture of the functions of
      mCR1/2.

PMID- 10904112
TI  - Phenotypes of complement knockouts.
AB  - Although complete and partial complement deficiencies are well described in
      humans and several spontaneous animal models, many questions have remained
      regarding the exact role that these deficiency states play in the observed
      clinical manifestations. Likewise, many important mechanistic questions cannot be
      addressed using patients or spontaneously arising animal models of deficiency
      states. To provide additional insights and create readily manipulable
      experimental systems, over the last 5 years mice have been created by several
      groups in which specifically targeted insertional mutagenesis has resulted in
      complete deficiencies of complement activation proteins, receptors or regulatory
      proteins. Many surprising findings have already been made using mice derived from
      these strategies, and clinically relevant studies have begun to provide great
      insights into human deficiency states. This review includes an overview of these
      complement deficient mice and highlights some of the important findings that have
      resulted from their creation. A discussion of future experimental directions
      thought to be important by this author then follows and concludes the review.

PMID- 10904113
TI  - Complement inhibitors: a resurgent concept in anti-inflammatory therapeutics.
AB  - In addition to its essential role in immune defense, the complement system
      contributes to tissue damage in many clinical conditions. Thus, there is a
      pressing need to develop therapeutically effective complement inhibitors to
      prevent these adverse effects. This concept, though old, received little
      scientific attention until recently. Data from animal models of diseases that
      have been produced using complement-deficient, knockout, and transgenic animals,
      as well as data demonstrating that complement proteins are produced in many
      important tissue sites (including the brain) have attracted the interest of many
      basic research scientists and applied scientists from the biotechnology field and
      larger pharmaceutical firms. This resurgence of interest has generated a wealth
      of new information in the field of complement inhibition. In this article, we
      comprehensively review up-to-date information in the field of complement
      inhibitors.

PMID- 10904114
TI  - Host recognition and target differentiation by factor H, a regulator of the
      alternative pathway of complement.
AB  - Factor H is responsible for recognition of host cells and tissues and mediates
      discrimination among microbial pathogens during activation of the alternative
      pathway of complement (AP). Its unique structure of 20 SCR domains arranged in a
      flexible chain permits a variety of functional sites to interact with complement
      proteins and surface markers in a biological example of single-molecule
      combinatorial chemistry. In addition to the complement regulatory site located in
      the N-terminal four SCR domains, two other sites bind complement protein C3b and
      three sites appear to recognize a variety of polyanions that serve as host
      markers. Recent studies indicate that cooperativity among several C3b- and
      polyanion-binding sites influences the biological functions of factor H and that
      the degree of influence of each site varies on different cells. The engagement of
      one or more of the host marker recognition sites enables factor H to control
      activation of the AP. The absence of host-like markers allows AP activation, but
      many common pathogens have developed receptors for factor H or mimics of host
      markers of varying degrees of authenticity allowing them to escape detection by
      this innate defense system. Organisms using one or more of these evasive
      techniques include Neisseria gonorrhoeae, Streptococcus pyogenes, Yersinia
      enterocolitica, Trypanosoma cruzi, and the HIV virus.

PMID- 10904115
TI  - C1q: structure, function, and receptors.
AB  - C1q is the first subcomponent of the C1 complex of the classical pathway of
      complement activation. Several functions have been assigned to C1q, which include
      antibody-dependent and independent immune functions, and are considered to be
      mediated by C1q receptors present on the effector cell surface. There remains
      some uncertainty about the identities of the receptors that mediate C1q
      functions. Some of the previously described C1q receptor molecules, such as gC1qR
      and cC1qR, now appear to have less of a role in C1q functions than in functions
      unrelated to C1q. The problem of identifying receptor proteins with complementary
      binding sites for C1q has been compounded by the highly charged nature of the
      different domains in C1q. Although newer candidate receptors like C1qR(p) and CR1
      have emerged, full analysis of the C1q-C1q receptor interactions is still at an
      early stage. In view of the diverse functions that C1q is considered to perform,
      it has been speculated that several C1q-binding proteins may act in concert, as a
      C1q receptor complex, to bring about C1q mediated functions. Some major advances
      have been made in last few years. Experiments with gene targeted homozygous C1q
      deficient mice have suggested a role for C1q in modulation of the humoral immune
      response, and also in protection against development of autoimmunity. The
      recently described crystal structure of Acrp-30, which is a serum protein
      secreted from adipocytes, has revealed a new C1q/TNF superfamily of proteins.
      Although the members of this superfamily may have diverse functions, there may be
      a common theme in their phylogeny and modular organisation of their distinctive
      globular domains.

PMID- 10904116
TI  - Complement components of the innate immune system in health and disease in the
      CNS.
AB  - The innate immune system and notably the complement (C) system play important
      roles in host defense to recognise and kill deleterious invaders or toxic
      entities, but activation at inappropriate sites or to an excessive degree can
      cause severe tissue damage. C has been implicated as a factor in the exacerbation
      and propagation of tissue injury in numerous diseases including neurodegenerative
      disorders. In this article, we review the evidence indicating that brain cells
      can synthesise a full lytic C system and also express specific C inhibitors (to
      protect from C activation and C lysis) and C receptors (involved in cell
      activation, chemotaxis and phagocytosis). We also summarise the mechanisms
      involved in the antibody-independent activation of the classical pathway of C in
      Alzheimer's disease, Huntington's disease and Pick's disease. Although the
      primary role of C activation on a target cell is to induce cell lysis
      (particularly of neurons), we present evidence indicating that C (C3a, C5a,
      sublytic level of C5b-9) may also be involved in pro- as well as anti
      inflammatory activities. Moreover, we discuss evidence suggesting that local C
      activation may contribute to tissue remodelling activities during repair in the
      CNS.

PMID- 10904117
TI  - Complement and innate immunity.

PMID- 10904118
TI  - Search for the influence of the tyrosine hydroxylase (TCAT)(n) repeat
      polymorphism on personality traits.
AB  - A putatively functional tetranucleotide repeat polymorphism in the tyrosine
      hydroxylase gene (TH) has been investigated with regard to different aspects of
      psychopathology. We investigated whether reported associations of this TH
      polymorphism may reflect associations with common personality traits. Personality
      was assessed by the NEO Personality Inventory-Revised version (NEO PI-R), in 205
      healthy Caucasian volunteers. Tendencies for higher scores in the neuroticism (N)
      facets, Angry hostility (P=0.008) and Vulnerability (P=0.021), were observed
      among carriers of one of the alleles (T8). Healthy women with the T6/T10 genotype
      had significantly higher scores (P=0.001) in the Deliberation and Dutifulness
      facets (P=0.031) (the Conscientiousness dimension, C) and lower scores (P=0.031)
      in the Feelings facet (the Openness dimension, O). We concluded that: (1) higher
      mean scores in the Neuroticism facets among T8 allele carriers are consistent
      with previous data and warrants further research; (2) the T6/T10 genotype may
      influence personality among women; (3) these data should be cautiously
      interpreted in the absence of corroborating data.

PMID- 10904119
TI  - A regulatory polymorphism of the monoamine oxidase-A gene may be associated with
      variability in aggression, impulsivity, and central nervous system serotonergic
      responsivity.
AB  - This study presents preliminary evidence of an association between polymorphic
      variation in the gene for monoamine oxidase-A (MAOA) and interindividual
      variability in aggressiveness, impulsivity and central nervous system (CNS)
      serotonergic responsivity. An apparently functional 30-bp VNTR in the promoter
      region of the X-chromosomal MAOA gene (MAOA-uVNTR), as well as a dinucleotide
      repeat in intron 2 (MAOA-CAn), was genotyped in a community sample of 110 men.
      All participants had completed standard interview and questionnaire measures of
      impulsivity, hostility and lifetime aggression history; in a majority of subjects
      (n=75), central serotonergic activity was also assessed by
      neuropsychopharmacologic challenge (prolactin response to fenfluramine
      hydrochloride). The four repeat variants of the MAOA-uVNTR polymorphism were
      grouped for analysis (alleles '1+ 4' vs. '2+3') based on prior evidence of
      enhanced transcriptional activity in MAOA promoter constructs with alleles 2 and
      3 (repeats of intermediate length). Men in the 1/4 allele group scored
      significantly lower on a composite measure of dispositional aggressiveness and
      impulsivity (P<0.015) and showed more pronounced CNS serotonergic responsivity
      (P<0.02) than men in the 2/3 allele group. These associations were also
      significant on comparison of the more prevalent one and three alleles alone
      (encompassing 93% of subjects). Although in linkage disequilibrium with the MAOA
      uVNTR polymorphism, MAOA-CAn repeat length variation did not vary significantly
      with respect to behavior or fenflluramine challenge in this sample. We conclude
      that the MAOA-uVNTR regulatory polymorphism may contribute, in part, to
      individual differences in both CNS serotonergic responsivity and personality
      traits germane to impulse control and antagonistic behavior.

PMID- 10904120
TI  - Antidepressant treatment during social challenge prior to 1 year of age affects
      immune and endocrine responses in adult macaques.
AB  - Antidepressants are widely used in treating depression and other behavioral
      problems in children and adolescents. Little is known about the long-term effects
      of these agents, particularly on physiological systems. The effects of previous
      antidepressant treatment during a social challenge in 9-month-old rhesus monkeys
      (Macaca mulatta) on their adult immune and endocrine responses were studied.
      Prior to the social challenge, the monkeys were reared either by their mother or
      in a peer group. Monkeys were treated with either a serotonergic agonist
      (fluoxetine), a noradrenergic agonist (desipramine), or saline during social
      separation. Non-separated, saline-treated monkeys served as control monkeys. In
      order to evaluate immune effects of early antidepressant treatment, adult monkeys
      were immunized with a novel antigen, tetanus toxoid. Blood samples were collected
      prior to and at 4-5-day intervals for 28 days after immunization. Plasma total
      immunoglobulins (IgG and IgM), complement levels (C3 and C4), tetanus antibody
      titers, and cortisol were assessed. Antibody levels were lowest in monkeys
      treated with antidepressants regardless of specific drug treatment or early
      rearing condition. Drug-treated subjects had elevated plasma immunoglobulins and
      complement protein levels. Cortisol was also highest in drug-treated subjects.
      These results should be considered when prescribing commonly used antidepressants
      for treatment of childhood disorders.

PMID- 10904121
TI  - Eye movement task measures inhibition and spatial working memory in adults with
      schizophrenia, ADHD, and a normal comparison group.
AB  - Schizophrenia and attention deficit/hyperactivity disorder (ADHD) are both
      associated with deficits in inhibition and working memory, although in ADHD the
      working memory deficit is hypothesized to be secondary to the inhibitory deficit.
      This similarity in cognitive processes has been paralleled by similarities across
      the two groups in the performance of working memory and inhibition tasks. The
      delayed oculomotor response task is an alternative task, which may allow greater
      separation of working memory from inhibitory components, and thus its use may
      provide additional information on primary vs. secondary deficits in these
      disorders. Ten young adult ADHD sufferers, 10 schizophrenic subjects, and 10
      normal subjects were matched on age, gender, and education. Eye movements were
      recorded during delayed oculomotor response tasks with 1- and 3-s delays. Both
      the ADHD and the schizophrenic subjects demonstrated dis-inhibition (an increased
      percentage of premature saccades); however only schizophrenic subjects
      demonstrated an impaired working memory (decreased spatial accuracy of the
      remembered saccade). The results are consistent with the hypothesis that working
      memory is a primary deficit in schizophrenia, but secondary to the inhibitory
      deficit in ADHD.

PMID- 10904122
TI  - Total sleep deprivation combined with lithium and light therapy in the treatment
      of bipolar depression: replication of main effects and interaction.
AB  - The clinical usefulness of total sleep deprivation (TSD) in the treatment of
      bipolar depression is hampered by a high-rate short-term relapse. Previous
      literature has suggested that both long-term lithium treatment and light therapy
      could successfully prevent relapse. We randomized 115 bipolar depressed
      inpatients to receive three cycles of TSD, alone or in combination with morning
      light exposure, given at an intensity of 150 or 2500 lux. Forty-nine patients
      were undergoing long-term treatment with lithium salts (at least 6 months), while
      66 patients were taking no psychotropic medication. Mood was self-rated by the
      Visual Analogue Scale three times a day during treatment. The results showed that
      both light therapy and ongoing lithium treatment significantly enhanced the
      effects of TSD on the perceived mood, with no additional benefit when the two
      treatments were combined. Subjective sleepiness during TSD, as rated by the self
      administered Stanford Sleepiness Scale, was significantly reduced by light
      exposure, and was correlated with the outcome. This study confirms the
      possibility of obtaining a sustained antidepressant response to TSD in bipolar
      patients.

PMID- 10904123
TI  - A comparison of alternative assessments of depressive symptom severity: a pilot
      study.
AB  - This study compared the performance of an itemized symptom self-report (Inventory
      of Depressive Symptomatology - Self-Report; IDS-SR), patient global ratings, and
      clinician global ratings with an itemized clinician-rated symptom severity
      measure (Inventory of Depressive Symptomatology - Clinician-Rated; IDS-C) in
      detecting treatment effects in patients with major depressive disorder (MDD). A
      total of 28 inpatients (30.8% psychotic) and 34 outpatients (17.9% psychotic)
      with MDD began treatment that followed the Texas medication algorithm. The
      clinicians completed the IDS-C and a Physician Global Rating Scale (PhGRS) at
      each assessment visit, while the patients completed the IDS-SR and a Patient
      Global Rating Scale (PtGRS). Change scores from the baseline to subsequent weeks
      were computed for all subjects, utilizing all four measures. The IDS-SR was a
      significant independent predictor of the response to treatment as compared to the
      two global ratings. The IDS-SR was as sensitive to change as the IDS-C. While the
      clinician-rated itemized symptom severity rating scale remains the standard to
      assess the symptomatic outcome of the treatment of MDD, a self-report of
      identical symptomatology may be a reasonable alternative for many patients.

PMID- 10904125
TI  - Prolactin response to TRH in patients with panic disorder.
AB  - The effects of TRH administration (400 microg, i.v.) on the release of prolactin
      were examined in 15 patients who met DSM-III-R criteria for panic disorder and 15
      normal control subjects. Four hundred micrograms TRH was given via IV route.
      Blood samples were taken before TRH administration (baseline values) and at 15,
      30 and 60 min. The results demonstrate that prolactin responses to TRH did not
      differ between panic disorder patients and normal control subjects. When only
      women were evaluated, the findings indicate that women with PD tend to show
      excessive prolactin responses to TRH. The findings are discussed in view of
      findings from earlier reports.

PMID- 10904124
TI  - Self-reported sensitivity to chemical exposures in five clinical populations and
      healthy controls.
AB  - Two hundred and twenty-five subjects, including normal volunteers and patients
      with previously documented seasonal affective disorder (SAD), chronic fatigue
      syndrome (CFS), Cushing's syndrome, Addison's disease and obsessive-compulsive
      disorder (OCD), completed a self-rated inventory of reported sensitivity to
      various chemical exposures. Patients with CFS, Addison's disease and SAD self
      reported more sensitivity to chemical exposures than normal controls. In
      addition, women reported more sensitivity than men. This report suggests that
      chemical sensitivity may be a relevant area to explore in certain medical and
      psychiatric populations. A possible relationship between reported chemical
      sensitivity and hypothalamic-pituitary-adrenal (HPA)-axis functioning is
      discussed.

PMID- 10904126
TI  - Presenilin-1 in late-onset depressive disorder.
AB  - Late-onset depressive disorder (LOD) is thought to be associated with dementia.
      Allele 1 in the presenilin-1 (PS-1) gene is a risk factor for Alzheimer's
      disease. An association study on this polymorphism was performed in depressive
      patients and control subjects. The patients were subdivided into those with early
      onset and late onset, using 50 years as the cut-off age. There was no
      statistically significant difference in the age of onset of depressive disorders
      according to the PS-1 genotype. There was also no association between early/late
      onset depressive disorders and the PS-1 genotype. Our results suggest there is no
      association between the PS-1 allele and LOD.

PMID- 10904127
TI  - Corrigendum to 'Neurophysiologic predictors of treatment response to fluoxetine
      in major depression'.

PMID- 10904128
TI  - The anti-oxidant ebselen antagonizes the release of the apoptogenic factor
      cytochrome c induced by Fe2+/citrate in rat liver mitochondria.
AB  - We studied the effects of ebselen (a seleno-organic anti-oxidant), on the release
      of the apoptogenic factor, cytochrome c, in two different experimental situations
      damaging mitochondria: (1) Fe(2+)/citrate, known to induce lipid peroxidation
      consecutively to an oxidative stress; and (2) atractyloside, a ligand of the
      adenine nucleotide translocator. The effects of ebselen were compared to those of
      butylated hydroxytoluene (BHT, an inhibitor of lipid peroxidation), and
      cyclosporine A (CsA, a classical pore antagonist). Ebselen, like BHT, inhibited
      Fe(2+)/citrate-induced release of cytochrome c, whereas CsA was inactive. On the
      contrary, neither ebselen nor BHT inhibited atractyloside-induced release of
      cytochrome c, whereas CsA was potently active. The antioxidant properties of
      ebselen may protect mitochondria from the consequences of the release of
      cytochrome c. Thus, it is suggested that the neuroprotective effect of ebselen
      previously demonstrated in humans and in animals may be due, at least in part, to
      a mitochondrial protection.

PMID- 10904129
TI  - A comparison of the patterns of striatal Fos-like immunoreactivity induced by
      various dopamine agonists in rats.
AB  - In contrast to the highly patchy patterns of Fos-like immunoreactivity seen in
      the rostral striatum after administration of a number of dopamine agonists, the
      monoamine uptake blocker cocaine has been reported to produce a relatively
      homogeneous pattern of gene expression. In the current study we extended these
      observations by using a quantitative technique to demonstrate that while
      amphetamine and apomorphine produce patchy striatal Fos expression, the selective
      dopamine uptake inhibitors amfonelic acid, nomifensine and GBR-12909 all, like
      cocaine, produce near random patterns of gene expression. These findings suggest
      that the production of relatively 'non-patchy' patterns of immediate early gene
      expression may be a general property of dopamine transport inhibitors unrelated
      to any unique pharmacological properties of cocaine.

PMID- 10904130
TI  - Relations between early prespike magnetic field changes, interictal discharges,
      and return to basal activity in the neocortex of rabbits.
AB  - To evaluate possible prespike field synchronizations, its relation to both
      interictal discharges and postspike return to baseline, penicillin-induced
      cortical interictal discharges were recorded in anaesthetized rabbits by
      magnetoencephalography (MEG) and electrocorticography (EcoG). Statistical
      parameters of spatial (global field power (GFP)) and temporal properties (Z
      parameter) of field synchronization were calculated. In our previous report,
      three types of prespike field synchronization were found before the onset of
      interictal spike. We report here that the continuous and fluctuating, but not the
      abrupt prespike increases, were more often associated with a spike and wave
      pattern of interictal discharge than with a spike alone. Furthermore, the
      postspike return of these statistical parameters shows the same three patterns as
      the prespike field synchronizations, but in the inverse time sequence. More often
      than not pre- and postspike pattern were of the same type. The results suggest an
      influence of prespike field synchronization upon interictal discharge and
      subsequent field return dynamics.

PMID- 10904131
TI  - Effects of footshock stress on superoxide dismutase and glutathione peroxidase
      enzyme activities and thiobarbituric acid reactive substances levels in the rat
      prefrontal cortex and striatum.
AB  - Mild footshock stress results in an increase dopamine metabolism in the
      prefrontal cortex. Increases in either the intensity or duration of stress
      enhance dopamine metabolism in the nucleus accumbens and striatum, as well as in
      the prefrontal cortex. Dopamine is metabolized by monoamine oxidase with hydrogen
      peroxide as a product. In this study we have demonstrated that while very mild
      (0.2 mA) footshock stress did not change glutathione peroxidase activity in the
      rat prefrontal cortex and striatum, more intense (1.6 mA) footshock stress
      increased glutathione peroxidase activity at 0, 15, 30 and 60 min after the
      footshock in the prefrontal cortex and at 30 min after the footshock in the
      striatum. Stress did not change superoxide dismutase activity and thiobarbituric
      acid reactive substances levels. These results indicate that increased dopamine
      metabolism induced by footshock stress is probably responsible for the increase
      of glutathione peroxidase activity.

PMID- 10904133
TI  - Carassius RFamide, a novel FMRFa-related peptide, is produced within the retina
      and involved in retinal information processing in cyprinid fish.
AB  - Carassius RFamide (C-RFa) is a novel peptide, isolated originally from the brain
      of the Japanese crucian carp and sharing homologies with mammalian prolactin
      releasing peptide (PrRP). It has been demonstrated previously that C-RFa mRNA is
      abundant in the proximal half (fundus) of the Japanese crucian carp eye. In the
      present work, we localized C-RFa by immunohistochemistry mainly to perikarya, in
      the proximal half of the inner nuclear layer (amacrine cell layer). This
      distribution is different from that of FMRFamide, which is confined to axon
      terminals of terminal nerve efferent fibers in the inner plexiform layer.
      Electrophysiological recording revealed that C-RFa depolarized some amacrine
      cells and hyperpolarized L-type horizontal cells in the carp. These results
      suggest that C-RFa is produced within the cyprinid retina and functions as a
      transmitter or neuromodulator in retinal image processing.

PMID- 10904132
TI  - Luteinizing hormone secretion elicited in a ligand-independent activation of
      progesterone receptor manner at pituitary level in the rat: differential effect
      of two selective estrogen receptor modulators.
AB  - In the absence of progesterone, RU486 reduced basal and luteinizing hormone
      releasing hormone (LHRH)-stimulated LH secretion in pituitaries from proestrous
      rats, a fact which evidences a ligand-independent activation of progesterone
      receptors (LIAPR) at pituitary level. This was also observed in pituitaries from
      rats treated with tamoxifen, and absent in glands from either ovariectomized or
      raloxifene-treated animals. Both ovariectomy or raloxifene treatment reduced the
      stimulatory effect of LHRH on LH secretion, while tamoxifen induced an even
      higher response. Prolactin (PRL) secretion was unaffected by either RU486 or
      LHRH, nor it was influenced by ovariectomy or raloxifene treatment. However,
      treatment with tamoxifen elevated PRL in all groups. These findings indicate that
      LIAPR is an estrogen-dependent phenomenon at the anterior pituitary of the female
      rat, and that tamoxifen and raloxifene present agonist and antagonist estrogen
      activity, respectively, at this level.

PMID- 10904134
TI  - Age-related change of neuropeptide Y-immunoreactive neurons in the rat main
      olfactory bulb.
AB  - The change of neuropeptide Y (NPY)-immunoreactive (IR) neurons in the rat main
      olfactory bulb as a result of aging was investigated at several aging stages over
      a two-year period; postnatal 1-24 months (P 1-P 24). From P 1 to P 12, the number
      of NPY-IR neurons and fibers increased with highest number in P 12, and the type
      of NPY-IR neurons had changed from bipolar neurons with short processes to
      bipolar/multipolar neurons with long processes. At P 24 the population of NPY-IR
      neurons and fibers had significantly decreased. Furthermore, the morphology of
      NPY-IR neurons showed a tendency to decrease in size and processes. It is
      suggested that the decrease of the number and size of NPY-IR neurons and fibers
      may underlie the age-related changes in the olfactory processes.

PMID- 10904135
TI  - Expression of neuronal nitric oxide synthase mRNA in stress-related brain areas
      after restraint in rats.
AB  - The objective of the present study was to investigate the expression of neuronal
      nitric oxide synthase (nNOS) mRNA in stress-related areas after restraint. Male
      Wistar rats (n=4-6/group) submitted to 2 h of restraint during one (acute) or
      seven (chronic) days were sacrificed 24 h after the last restraint period. In
      situ hybridisation was performed with oligonucleotide probes radiolabeled with
      (35)S. Acute restraint induced a significant increase in nNOS mRNA in the
      paraventricular hypothalamic nucleus (PVN), medial parvocellular part,
      dorsolateral periaqueductal grey (DLPAG) and medial amygdaloid nucleus, but not
      in the hippocampal formation. This effect persisted after chronic restraint in
      the PVN and DLPAG. These results suggest that restraint stress induces changes in
      gene expression of nNOS in areas related to stress reactions.

PMID- 10904136
TI  - Adenosine A2A receptor facilitation of synaptic transmission in the CA1 area of
      the rat hippocampus requires protein kinase C but not protein kinase A
      activation.
AB  - Adenosine is a neuromodulator in the hippocampus acting mainly via inhibitory
      A(1) receptors but also via facilitatory A(2A) receptors. We now investigated the
      transducing system operated by hippocampal A(2A) receptors. The selective A(2A)
      receptor agonist, CGS 21680 (10 nM), facilitated synaptic transmission by 14%, an
      effect not modified by the phosphodiesterase IV inhibitor, rolipram (30 microM),
      or by the adenylate cyclase activator, forskolin (3 microM), or by the protein
      kinase A inhibitor, HA-1004 (10 microM), but nearly abolished by the protein
      kinase C inhibitors, chelerythrine (6 microM) or bisindolylmaleimide I (1
      microM). Inhibition of protein kinase C also prevented the A(2A) receptor-induced
      attenuation of A(1) receptor-mediated inhibition of hippocampal synaptic
      transmission. These results indicate that adenosine A(2A) receptor facilitation
      of hippocampal synaptic transmission involves protein kinase C rather than
      protein kinase A activation.

PMID- 10904137
TI  - Apomorphine-induced aggressive behaviour and post-mortem monoamine content in
      male Wistar rats.
AB  - The aim of this study was to investigate the monoamine content in post-mortem
      brain samples of control, apomorphine-aggressive, and apomorphine-non-aggressive
      adult male Wistar rats. The repeated apomorphine (1.0 mg/kg, (s.c.) once daily
      during 2 weeks) gradually induced aggressive behaviour in 18 animals out of 24.
      No unidirectional changes in the brain monoamine contents in four regions
      (frontal cortex, striatum, hippocampus, and hypothalamus) were detected as
      measured by high pressure liquid chromatography-electrochemical detection. In
      conclusion, our present experiment demonstrates that the development and
      intensity of apomorphine-induced aggressive behaviour do not correlate with the
      brain post-mortem monoamine content.

PMID- 10904138
TI  - The dynamic processes for word and picture encoding in the human brain as
      revealed by magnetoencephalography.
AB  - Subjects were asked to memorize either the size or the meaning of the first
      stimulus (encoding) of a stimulus pair, and to match it to the second stimulus.
      Words and pictures were used as the stimuli in separate tests. Two components
      named 1M and 2M in both hemispheres for word or picture stimuli could be detected
      by magnetoencephalography (MEG). The dipole location of 1M in bilateral
      hemispheres for words is different from that for pictures, but that of 2M is not.
      It is considered that picture and word are processed in different systems at the
      initial stage, mainly in the lateral temporal cortex for words and in the
      parietal cortex for pictures, whereas they are processed in a common semantic
      system at the late stage.

PMID- 10904139
TI  - Testosterone metabolites in patients reduce the levels of very long chain fatty
      acids accumulated in X-adrenoleukodystrophic fibroblasts.
AB  - Testosterone metabolites (dihydrotestosterone, DHT) and 5 alpha-androstan-3
      alpha,17 beta-diol (3 alpha-diol), but not testosterone itself, were shown to
      reduce the levels of very long chain fatty acids which accumulate in cultured
      skin fibroblasts from X-adrenoleukodystrophic patients (X-ALD). In addition, in X
      ALD fibroblasts, testosterone is less actively converted into DHT vs. controls
      (skin fibroblasts retrieved from normal subjects) whereas the additional
      conversion of DHT to the final product 3 alpha-diol is enhanced. This is the
      first report of altered testosterone metabolism in X-ALD fibroblasts and of the
      effects of androgens in lowering the abnormal accumulation of very long chain
      fatty acids in this type of cells.

PMID- 10904140
TI  - Muscular exercise improves knee position sense in humans.
AB  - To determine how position sense depends on the functional state of the receptors
      involved, we assessed the accuracy of knee position sense before and after a
      moderate exercise on a cycle ergometer. Measurements were done on 32 healthy
      subjects with four protocols combining two tasks (intramodal: using the
      contralateral leg, and crossmodal: using a scheme of a leg on a screen) and two
      ways of positioning (active and passive). Results showed an improved position
      sense after exercise with the intramodal protocol combined with active
      positioning of the reference leg. Whatever the mechanisms involved, enhanced
      motor performances after exercise can be due not only to improved mechanical
      properties of the muscles but also to better kinesthetic sensibility.

PMID- 10904141
TI  - Decreased frontal lobe ratio of N-acetyl aspartate to choline in familial
      schizophrenia: a proton magnetic resonance spectroscopy study.
AB  - Neuropathological and neuroimaging studies suggest neuronal dysfunction in
      schizophrenia. N-acetyl aspartate (NAA) is a useful marker of neuronal
      dysfunction that can be measured with magnetic resonance spectroscopy (MRS). In
      the present study NAA, choline (Cho), phospho-creatine ((P)Cr), inositol
      containing compounds and glutamine/glutamate (Glx) were assessed in the left
      frontal lobe and basal ganglia of subjects with familial schizophrenia, family
      members with mixed psychiatric diagnoses, unaffected family members, and
      community controls. Concentrations of metabolites were analyzed and expressed as
      ratios. NAA/Cho, NAA/(P)Cr and Glx containing compounds showed a negative
      correlation with age in the frontal lobe. After covarying for age, subjects with
      schizophrenia had a significant reduction in the left frontal lobe NAA/Cho ratio
      compared with unaffected family members (P=0.018) as well as with community non
      familial (P=0.037) controls. These MRS observations support the hypothesis of a
      disease-related neuronal deficit in the frontal lobe of schizophrenic patients,
      and relatively normal basal ganglia.

PMID- 10904143
TI  - The traditional uses, chemical constituents and biological activities of Plantago
      major L. A review.
AB  - Plantago major L. leaves have been used as a wound healing remedy for centuries
      in almost all parts of the world and in the treatment of a number of diseases
      apart from wound healing. These include diseases related to the skin, respiratory
      organs, digestive organs, reproduction, the circulation, against cancer, for pain
      relief and against infections. P. major contains biologically active compounds
      such as polysaccharides, lipids, caffeic acid derivatives, flavonoids, iridoid
      glycosides and terpenoids. Alkaloids and some organic acids have also been
      detected. A range of biological activities has been found from plant extracts
      including wound healing activity, anti-inflammatory, analgesic, antioxidant, weak
      antibiotic, immuno modulating and antiulcerogenic activity. Some of these effects
      may attribute to the use of this plant in folk medicine.

PMID- 10904142
TI  - alpha-Melanocyte stimulating hormone prevents fasting-induced suppression of
      corticotropin-releasing hormone gene expression in the rat hypothalamic
      paraventricular nucleus.
AB  - During fasting, corticotropin-releasing hormone (CRH) mRNA decreases in the
      hypothalamic paraventricular nucleus (PVN), but the mechanism by which this takes
      place is not well understood. To test the hypothesis that the melanocortin system
      may be involved in the regulation of CRH mRNA in the PVN during fasting, the
      effect of intracerebroventricularly administered alpha-melanocyte stimulating
      hormone (MSH) on CRH mRNA in the PVN was studied in fasted animals by in situ
      hybridization histochemistry. Whereas fasting suppressed CRH mRNA levels in the
      PVN, alpha-MSH at doses of 150 and 300 ng every 6 h for 64 h prevented the
      fasting-induced suppression of CRH gene expression in the PVN. These data
      indicate that the suppression of alpha-MSH synthesis may be responsible for the
      decreased CRH gene expression in the PVN during fasting.

PMID- 10904144
TI  - Review on some plants of Indian traditional medicine with antioxidant activity.
AB  - A lot of medicinal plants, traditionally used for thousands of years, are present
      in a group of herbal preparations of the Indian traditional health care system
      (Ayurveda) named Rasayana proposed for their interesting antioxidant activities.
      Among the medicinal plants used in ayurvedic Rasayana for their therapeutic
      action, some of these have been throughly investigated. In the present paper
      seven plants (Emblica officinalis L., Curcuma longa L., Mangifera indica L.,
      Momordica charantia L., Santalum album L., Swertia chirata Buch-Ham, Withania
      somnifera (L.) Dunal) are viewed for their historical, etymological,
      morphological, phytochemical and pharmacological aspects. The plants described
      contain antioxidant principles, that can explain and justify their use in
      traditional medicine in the past as well as the present. In order to identify the
      plants with antioxidant activity in Ayurveda, a formulation of some rasayanas
      with well defined antioxidant properties has been examinated. For this purpose,
      we have considered Sharma's work on the preparation MAK4, MAK5, MA631, MA 471, MA
      Raja's Cup, MA Student Rasayana, MA Ladies Rasayana.

PMID- 10904145
TI  - Evidence for protective and antioxidant properties of rutin, a natural flavone,
      against ethanol induced gastric lesions.
AB  - This study was designed to determine the ulcer-protecting effects of rutin, a
      natural flavone, against gastric lesions induced by 50% ethanol, the experimental
      model related to lesion pathogenesis with production of reactive species. The
      possible involvement of sulphydryl compounds (SH), neutrophil infiltration, and
      the capacity of this flavone to restrain the oxidative process produced in the
      gastric tissue were also investigated. The levels of thiobarbituric acid (TBA, as
      index of lipid peroxidation), the myeloperoxidase activity (MPO, as a marker of
      neutrophil infiltration), the content of mucosal sulphydryls (SH) groups and the
      activity of glutathione peroxidase (GSH-Px, an important antioxidant enzyme) were
      determined. Pretreatment with the highest dose of rutin (200 mg/kg), 120 min
      before 50% ethanol, resulted in the most effective necrosis prevention. TBA
      reactive substances in the gastric mucosa, were increased by ethanol injury, and
      this increase was inhibited by the administration of 200 mg/kg of rutin. However,
      the flavonoid was not able to modify the ethanol-induced neutrophil infiltrate
      expressed as myeloperoxidase activity. Exposure of the gastric mucosa to 50%
      ethanol induced a significant diminution in gastric non-protein SH content; this
      parameter also was not modified by the treatment with rutin. GSH-Px activity
      decreased in the gastric mucosa after ethanol-treatment. In contrast, rutin at
      all tested doses induced a significant increase in this enzymatic activity,
      higher than in control group. These results suggest that the gastroprotective
      effect of rutin in this experimental model appears through an anti-lipoperoxidant
      effect, and also by enhancement of the anti-oxidant enzymatic (GSH-Px) activity.

PMID- 10904146
TI  - Augmentation of natural killer cell activity in vitro against tumor cells by wild
      plants from Jordan.
AB  - Thirteen aqueous extracts prepared from Jordanian plants, that are currently used
      in traditional medicine to treat various types of cancer, were tested in mice for
      their ability to augment natural killer (NK) cell function in vitro in generating
      cytotoxicity against YAC tumor targets. Lymphoid cells at a concentration of
      5x10(6)/ml were incubated in medium alone or in medium containing different
      dilutions of either plant extract or purified interferon alpha for 20 h and
      tested for NK activity. Maximum NK activity (62. 3%) was obtained at 1:50
      dilution of Nigella sativum fresh aqueous extract, 48.5% at 1:100 dilution for
      Allium sativum (and 38.3% at 1:50 dilution for Onopordum acanthium. Fresh aqueous
      plant extracts appeared to be more potent than old dried aqueous extract or
      ethanolic extracts. NK augmentation by plant extracts using nylon wool non
      adherent spleen cells was slightly higher than the whole spleen cells.

PMID- 10904147
TI  - Anticonvulsive activity of Albizzia lebbeck, Hibiscus rosa sinesis and Butea
      monosperma in experimental animals.
AB  - The ethanolic extracts of leaves of Albizzia lebbeck and flowers of Hibiscus rosa
      sinesis and the petroleum ether extract of flowers of Butea monosperma exhibited
      anticonvulsant activity. The bioassay guided fractionation indicated that the
      anticonvulsant activity lies in the methanolic fraction of chloroform soluble
      part of ethanolic extract of the leaves of A. lebbeck, acetone soluble part of
      ethanolic extract of H. rosa sinesis flowers and acetone soluble part of
      petroleum ether extract of B. monosperma flowers. The fractions protected animals
      from maximum electro shock, electrical kindling and pentylenetetrazole-induced
      convulsions in mice. The fractions also inhibited convulsions induced by lithium
      pilocarpine and electrical kindling. However, they failed to protect animals from
      strychnine-induced convulsions. The fractions antagonised the behavioral effects
      of D-amphetamine and potentiated the pentobarbitone-induced sleep. The fractions
      raised brain contents of gamma-aminobutyric acid (GABA) and serotonin. These
      fractions were found to be anxiogenic and general depressant of central nervous
      system.

PMID- 10904148
TI  - Anti-ulcerogenic effect of Momordica charantia L. fruits on various ulcer models
      in rats.
AB  - The mature fruits of Momordica charantia L. (Cucurbitaceae) are used externally
      for the rapid healing of wounds and internally for the treatment of peptic ulcers
      in Turkish folk medicine. For the evaluation of the latter activity, ethanol
      induced ulcerogenesis model in rats was employed. The olive oil extract of the
      material as well as dried-powdered fruits in filtered honey showed significant
      and dose-dependent anti-ulcerogenic activity against this model. A potent and
      dose-dependent inhibitory activity was also observed by the administration of
      ethanol extract of the fruits. For the bioassay-guided fractionation, the
      material was first extracted with hexane and then by ethanol and both extracts
      were found active against the same ulcer model. Furthermore, ethanol extract of
      the fruits showed significant activity against HCl-EtOH induced ulcerogenesis in
      indomethacin-pretreated rats and diethyldithiocarbamate-induced ulcer models.

PMID- 10904149
TI  - Antimicrobial investigation of semipurified fractions of Ginkgo biloba leaves.
AB  - A total methanolic extract of Ginkgo biloba leaves was fractionated by solvent
      partition using ethyl acetate (fraction A), n-butanol (fraction B) and water
      (fraction C). The antimicrobial activity of the three fractions was evaluated
      using a number of Gram-positive and -negative bacteria and yeasts. The apolar
      fraction A appeared to be the most interesting because of its activity against
      several microorganisms; this fraction was further separated by high performance
      liquid chromatography, and shown to contain substances with strong inhibitory
      activity against Enterococcus faecalis 31, different from the major known
      chemical components of G. biloba leaves.

PMID- 10904150
TI  - Immunostimulant activity of dry fruits and plant materials used in indian
      traditional medical system for mothers after child birth and invalids.
AB  - Products of certain plants given to mothers after child birth or to invalids were
      studied for immunostimulant activity using the macrophage migration index (MMI)
      as a parameter of macrophage activation and cell-mediated immunity and
      haemagglutinating antibody (HA) titres and plaque-forming cell (PFC) counts as
      parameters of humoral immunity. Feeding of Prunus amygdalus (Almond(1)) and
      Buchanania lanzan (Chirronji(1)) significantly stimulated both CMI and humoral
      immunity in BALB/c mice as evidenced by the enhancement of MMI, HA titres, and
      PFC counts. Euryale ferox (Tel makhana(1)), Phoenix dactylifera (Chhohara(1)) and
      Zingiber officinale (Sonth(1)), however, stimulated humoral immunity to a greater
      extent than CMI. The observation provides scientific basis for feeding the
      products of above plants to mothers after child birth and to invalids with a
      relatively poor immune status.

PMID- 10904151
TI  - The wound healing properties of Channa striatus-cetrimide cream-- tensile
      strength measurement.
AB  - Channa striatus, a fresh water snakehead fish, is reported to enhance dermal
      wound healing. Biochemical components such as amino acids and fatty acids are
      important for the synthesis of collagen fibers during wound healing. Arachidonic
      acid, a precursor of prostaglandin plays a vital role in healing the wounds.
      Haruan (C. striatus) contains all the essential amino acids for wound healing
      particularly glycine as well as high contents of arachidonic acid and
      polyunsaturated fatty acids that can promote prostaglandin synthesis. In the
      present work we have studied the wound healing effect of C. striatus in Sprague
      Dawley rats. Cream formulations having different haruan fish extract
      concentrations as the active ingredient were prepared and stabilized, and they
      were applied to the wounds. The healing of wounds was characterized by an
      increase in the tensile strength of the skin, determined on the 7th post
      operative day in each case. Haruan treatment of wounds promotes remodeling of
      collagen, by the synthesis of inter- and intra-molecular protein crosslinking and
      thus produces a marked increase (P<0.05) in tensile strength as compared to the
      cetrimide treated group. On the basis of our experiment we conclude that C.
      striatus helps in wound healing as indicated by the increase in tensile strength.
      We hypothesise that this effect may be due to its high content of arachidonic
      acid, glycine and polyunsaturated fatty acids. The mechanism of wound healing
      will be investigated in future studies.

PMID- 10904152
TI  - In vitro screening of american plant extracts on Trypanosoma cruzi and
      trichomonas vaginalis.
AB  - From the beginning of this decade and with the revival of the phytotherapy,
      biological research about immunomodulatory, anti-inflammatory and antiprotozoal
      effects of Central and South American plants have been in progress. Our objective
      was to determine the antiprotozoal activity of 79 extracts from different plant
      families, including Asteraceae, Araceae, Moraceae, Solanaceae, Rhamnaceae,
      Zingiberaceae, Leguminosae and Sapotaceae. Once matching with herbarium specimens
      authenticated the plants, selected parts were separated, dried carefully and
      reduced to powder. Most of the screened extracts were aqueous. Two protozoa with
      different metabolic pathways, Trypanosoma cruzi and Trichomonas vaginalis were
      used as experimental models. Trypanocidal activity of plants was assayed on
      epimastigote cultures in liver infusion tryptose (LIT). Anti-Trichomonas activity
      was determined over cultures of the parasite in Diamond medium. In both cases,
      microscopic counting of parasites, after their incubation in the presence of
      different concentrations of the crude extracts, were made in order to determine
      the cytocidal and cytostatic activities respect to control cultures. Of the nine
      extracts that showed antiprotozoal activity, those from Mikania cordifolia and
      Philodendron bipinnatifidum were then fractionated, and again, were assayed the
      organic and aqueous phases obtained.

PMID- 10904153
TI  - Comparison of the free radical-scavenging activity of propolis from several
      regions of Argentina.
AB  - Propolis is extensively used in Argentine folk medicine. Alcoholic extracts of
      propolis from different regions of Argentina were prepared. The extracts were
      analysed for the determination of total flavonoid content (from 13.3 to 42.6 mg/g
      of propolis) by using the aluminum nitrate method, UV spectrophotometry and thin
      layer chromatography. All of them contained high total flavonoid content. It was
      also observed that all samples of ethanolic extracts of propolis showed free
      radical-scavenging activity in terms of scavenging of the radical DPPH but the
      highest activities were found for samples from Tucuman and Santiago del Estero.
      In all cases with 20 microg/ml of soluble principles, the percentage of DPPH
      degradation was different (Banda Oeste: 67.5%; Veronica: 45%; Forres: 35%; Saenz
      Pena: 20% and Juan Jose Castelli: 55%). These results may justify their use as a
      source of natural antioxidants.

PMID- 10904154
TI  - Andrographis paniculata (Nees) selectively blocks voltage-operated calcium
      channels in rat vas deferens.
AB  - The possible blockade of voltage-operated calcium channels (VOCs) by Andrographis
      paniculata dried extract in vas deferens smooth muscle was investigated in rats.
      The tissues were incubated in Ca(2+)-free Kreb's solution and stimulated with KCl
      (40 mM) to produce depolarisation of the membrane. The isometric contractile
      response to cumulative concentrations of CaCl(2) was effectively blockaded by 0.2
      and 0.4 mg/ml A. paniculata. In other experiments, the maximum contractile
      response induced by norepinephrine was not antagonised by 0.2, 0.4 or 0.8 mg/ml
      A. paniculata. The possible blockade of Ca(2+) entry by A. paniculata was
      evaluated with 45Ca(2+) uptake in vas deferens treated with reserpine (5 and 2.5
      mg/kg) 48 and 24 h before the experiments. Epididymal segments were incubated
      with Ca(2+)-free Kreb's solution with KCl, 25 and 50 mM. The influx was
      completely blockaded with 0.4 mg/ml A. paniculata. These results suggest that A.
      paniculata selectively blockades VOCs, hence inhibiting the 45Ca(2+) influx.

PMID- 10904155
TI  - A search for natural bioactive compounds in Bolivia through a multidisciplinary
      approach. Part III. Evaluation Of the antimalarial activity of plants used by
      Altenos Indians.
AB  - A total of 40 plant extracts traditionally used by the Altenos Indians, a native
      community living between the Andean block and the tropical valleys of Bolivia,
      were screened for antimalarial activity in vitro on Plasmodium falciparum
      chloroquine resistant (Indo) strain, and in vivo on rodent malaria Plasmodium
      vinckei petteri. Eleven extracts displayed good or moderate activity in vivo, and
      ten extracts good or very good antimalarial activity in vitro. Results of the
      screening are discussed here, in relation with the traditional use of plants.

PMID- 10904156
TI  - Effects of Kampo medicine, Toki-shakuyaku-san (Tang-Kuei-Shao-Yao-San), on
      choline acetyltransferase activity and norepinephrine contents in brain regions,
      and mitogenic activity of splenic lymphocytes in ovariectomized mice.
AB  - We investigated the effects of Toki-shakuyaku-san (TSS, Tang-Kuei-Shao-Yao-San in
      Chinese), Japanese traditional herbal medicine, on the nervous and immune systems
      in ovariectomized mice as a climacteric disorder model. Female C57BL/6 mice were
      ovariectomized (OVX) and TSS was given daily through the drinking water for
      either 10 or 20 days from the day after ovariectomy. After completion of
      experimental sessions, animals were sacrificed and specific brain regions were
      assayed for choline acetyltransferase (ChAT) activity and norepinephrine
      contents. The mitogenic activities, alkaline phosphatase activity and 3-(4, 5
      dimethyl-2-thiazolyl)-2,5-diphenyl-2H terazolium bromide (MTT) activity, in
      splenic lymphocytes has also measured. Furthermore, the effects of TSS on
      learning and memory ability were studied by the step-through type passive
      avoidance test. As the results, the administration of TSS significantly
      suppressed the decrease of ChAT activity in the cerebral cortex (CC) and the
      dorsal hippocampus (DH) of ovariectomized mice at 10 days after ovariectomy,
      however no significant effect was observed at 20 days after ovariectomy.
      Norepinephrine contents in OVX group were decreased at 10 and 20 days after
      ovariectomy in the CC and the ventral hippocampus (VH). The administration of TSS
      significantly suppressed the decrease of norepinephrine contents at 20 days after
      ovariectomy. The mitogenic activities of lymphocyte in spleen were increased at
      10 days after ovariectomy, and decreased at 20 days after ovariectomy. However,
      the suppression of these changes was observed in the group given TSS. The mean
      latent period was also shortened in the passive avoidance test in the OVX group,
      but TSS treated group improved mean latency. From these observations, it is
      inferred that administration of TSS brings on the synthesis of acetylcholine and
      norepinephrine in the CC and hippocampus, and may improve the memory related
      behavior and the abnormalities in lymphocytes in the models of the climacteric
      disorder.

PMID- 10904157
TI  - Cytotoxic and DNA interaction activities of extracts from medicinal plants used
      in Argentina.
AB  - Eight crude extracts from seven Argentine plants with cancer-related
      ethnobotanical uses have been subjected to a bioscreening study to detect
      cytotoxic activity. The plants studied were: Aristolochia triangularis, Baccharis
      grisebachii, Bolax gummifera, Eupatorium hecatanthum, Erythrina crista-galli,
      Pterocaulon polystachium and Salpichroa origanifolia. Crown gall tumour
      inhibition, DNA interaction and cytotoxicity towards KB cells were assayed using
      the potato disc, the DNA-methyl green (DNA-MG) and the KB cells cytotoxicity
      bioassays respectively. The results obtained indicate that A. triangularis
      (ED50=47 microg/ml), B. gummifera (ED50=32 microg/ml) and E. hecatanthum (ED50=35
      microg/ml) contained cytotoxic compounds against KB cells. All of the plants
      studied inhibited the growth of crown gall tumours, showing correlation between
      the experimental data and the uses reported for these plants. Moreover, the
      results obtained for the extracts of E. hecatanthum and P. polystachium indicate
      the presence of compounds that interact with DNA (48 and 22% of absorbance
      decrease, respectively). The results obtained suggest that cytotoxicity could
      play an important role in the activities claimed for the plants under study.

PMID- 10904158
TI  - Studies on the anti-inflammatory and related pharmacological properties of the
      aqueous extract of Bridelia ferruginea stem bark.
AB  - The anti-inflammatory profile of the aqueous extract of Bridelia ferruginea stem
      bark was investigated using both in vivo and in vitro models. The extract
      exhibited strong topical anti-inflammatory effect shown as inhibition of croton
      oil-induced ear oedema in mice, and reduced hind-paw swelling and growth
      retardation in the adjuvant-induced arthritis model in rats, following oral
      administration at 10, 20, 40 or 80 mg/kg. The extract (10-80 mg/kg, p.o.) caused
      an inhibition of increase in vascular permeability in both cyclophosphamide
      induced haemorrhagic cystitis and acetic acid-induced vascular permeability in
      rats and mice, respectively. B. ferruginea produced stabilization of erythrocytes
      exposed to heat and stress-induced lysis. Antipyretic and analgesic properties of
      the extract were also observed.

PMID- 10904159
TI  - Ethnopharmacological evaluation of the anticonvulsant, sedative and antispasmodic
      activities of Lavandula stoechas L.
AB  - Lavandula stoechas L. (Lamiaceae) has been used for a long time in traditional
      medicine as an anticonvulsant and antispasmodic. The aqueous-methanolic extract
      of L. stoechas flowers (LS) was studied for its possible anticonvulsant and
      antispasmodic activities. When tested in mice, LS (600 mg/kg) significantly
      reduced the severity and increased the latency of convulsions induced by
      pentylene tetrazole (PTZ). LS likewise reduced PTZ's lethality. LS up to a dose
      of 600 mg/kg was found devoid of any hypnotic effect in mice, however, animals
      were found to be dull, calm and relaxed. The sedative effect of the plant extract
      was confirmed, as it prolonged the pentobarbital sleeping time in mice similar to
      that of diazepam. In isolated rabbit jejunum preparations, LS caused a dose
      dependent (0.1-1.0 mg/ml) relaxation of spontaneous contractions. LS also
      inhibited K(+)-induced contractions in a similar dose range, thereby suggesting
      calcium channel blockade. This effect was confirmed when pretreatment of the
      jejunum preparation with LS produced a dose-dependent shift of the Ca(2+) dose
      response curve to the right, similar to the effect of verapamil, a standard
      calcium channel blocker. These data indicate that the plant extract exhibits
      anticonvulsant and antispasmodic activities. Its calcium channel blocking
      property may be mechanistically related to these activities. Its usefulness in
      folk medicine appears thus to be based on a sound mechanistic background.

PMID- 10904160
TI  - Hypoglycaemic effect of spergularia purpurea in normal and streptozotocin-induced
      diabetic rats.
AB  - Single and repeated oral administration of the water extracts of Spergularia
      purpurea (SP) at a dose of 10 mg/kg were tested on hypoglycaemic activity in
      normal and streptozotocin-induced diabetic rats. In normal rats, the water
      extract of SP decreased significantly the plasma glucose levels 4 h after single
      oral administration (P<0.01), and one week after repeated oral administration
      (P<0.05). A significant decrease of plasma glucose levels was observed 6 h after
      a single oral administration of the water extract of S. purpurea in severe
      hyperglycaemic rats (n=6) from 22.78+/-0.60 to 11.21+/-0.49 mmol/l (P<0.001). On
      other hand, water extract of S. purpurea normalised plasma glucose levels after
      two weeks of repeated oral administration in diabetic rats; 24.05+/-1.16 versus
      7.18+/-0.51 mmol/l (P<0.001) at the start and 2 weeks after water extract
      administration, respectively. We conclude that the water extract of SP induces
      hypoglycaemic activity when administered orally in normal and STZ diabetic rats.
      In order to determine the active principle (s) responsible of the hypoglycaemic
      effect, preliminary phytochemical analysis of the water extract has been
      investigated.

PMID- 10904161
TI  - Studies on the anti-inflammatory, antipyretic and analgesic properties of
      Alstonia boonei stem bark.
AB  - The methanol extract of the stem bark of Alstonia boonei was investigated for
      anti-inflammatory property. The analgesic and antipyretic properties of the
      extract was also evaluated. The extract caused a significant (P<0.05) inhibition
      of the carrageenan-induced paw oedema, cotton pellet granuloma, and exhibited an
      anti-arthritic activity in rats. Vascular permeability induced by acetic acid in
      the peritoneum of mice was also inhibited. The extract also produced marked
      analgesic activity by reduction of writhings induced by acetic acid, as well as
      the early and late phases of paw licking in mice. A significant (P<0.05)
      reduction in hyperpyrexia in mice was also produced by the extract. This study
      has established anti-inflammatory, analgesic and antipyretic activities of the
      stem bark of A. boonei.

PMID- 10904162
TI  - Antispasmodic and anti-diarrhoeal effect of Satureja hortensis L. essential oil.
AB  - Satureja hortensis L. (Lamiaceae) is an annual herb that is used in the
      traditional medicine of Iran for treating stomach and intestinal disorders. The
      antispasmodic activity of S. hortensis essential oil (SHEO) was assessed on
      contractions of isolated ileum, induced by KCl and acetylcholine, and compared
      with the effect of atropine and dicyclomine. SHEO inhibited the response to 80 mM
      KCl in a concentration-dependent manner (pD(2)=1.55+/-0.09 microg/ml; this is
      negative log concentration of SHEO causing 50% of maximum inhibition) and
      attenuating the maximum inducible response of acetylcholine concentration
      response curve. Effect of SHEO on KCl was similar to that of dicyclomine.
      Dicyclomine (3.46 and 34.6 ng/ml) also reduced the response to acetylcholine on
      rat isolated ileum without altering the maximum response and shifted the
      acetylcholine concentration-response curve to the right by 16-fold at 34.6 ng/ml
      (100 nM) bath concentration, while atropine only inhibited the response to
      acetylcholine. This study shows that SHEO is a relaxant of rat isolated ileum. In
      addition to antispasmodic activity in vitro, essential oil of this plant at a
      dose of 0.1 ml/100 g inhibited castor oil induced diarrhoea in mice. As the
      inhibition of contractile overactivity of the ileum is the base of the treatment
      of some gastrointestinal disorders such as colic, SHEO may have clinical benefits
      for treatment of these conditions.

PMID- 10904163
TI  - Immunomodulatory activity of Withania somnifera.
AB  - Administration of an extract from the powdered root of the plant Withania
      somnifera was found to stimulate immunological activity in Babl/c mice. Treatment
      with five doses of Withania root extract (20 mg/dose/animal; i.p.) was found to
      enhance the total WBC count (17125 cells/mm(3)) on 10th day. Bone marrow
      cellularity (27x10(6) cells/femur) as well as alpha-esterase positive cell number
      (1800/4000 cells) also increased significantly (P<0.001) after the administration
      of Withania extract. Treatment with Withania extract along with the antigen
      (SRBC) produced an enhancement in the circulating antibody titre and the number
      of plaque forming cells (PFC) in the spleen. Maximum number of PFC (985 PFC/10(6)
      spleen cells) was obtained on the fourth day. Withania extract inhibited delayed
      type hypersentivity reaction in mice (Mantoux test). Administration of Withania
      extract also showed an enhancement in phagocytic activity of peritoneal
      macrophages (76.5 pigmented cells/200) when compared to control (31.5/200 cells)
      in mice. These results confirm the immunomodulatory activity of W. somnifera
      extract, which is a known immunomodulator in indigenous medicine.

PMID- 10904164
TI  - Traditional Tongan cures for morning sickness and their mutagenic/toxicological
      evaluations.
AB  - Every year millions of women become pregnant, and more than 60% of them will
      develop some form of morning sickness. Yet drugs like Thalidomide, Bendectin and
      other possibly potent teratogens administered for pre-partum nausea have severely
      limited any medicinal intervention. In Tonga, women have been treated for morning
      sickness for hundreds of years. Two types of traditional treatments exist, the
      first one consists of an infusion of fresh leaves, commonly called vai momoko.
      The second type of treatment is called vai haka, which is made from the boiled
      bark of several trees. In this paper we describe the results of 6 months of
      intensive interviews in Tonga regarding the second type of treatment called vai
      haka. In addition, we tested vai haka for mutagenic and teratogenic effects. Data
      from the Ames TA-98 mutagenic bioassay clearly indicate that vai haka is not
      mutagenic with or without S-9 activation. Twenty-six experimental CD-1 white mice
      were gavaged with 0.1 ml of vai haka (at 540xthe human dose) while the control
      group of 17 mice were gavaged with 0.1 ml of water to determine teratogenic and
      developmental effects of the vai haka. No significant teratogenic or
      developmental anomalies occurred in the mice dosed with vai haka compared to the
      controls.

PMID- 10904165
TI  - Antinociceptive mechanisms of dipsacus saponin C administered intrathecally in
      mice.
AB  - Dipsacus saponin C (DSC) administered intrathecally (i.t.) showed antinociceptive
      effect in a dose-dependent (from 3.75 to 30 microg) manner as measured by the
      tail-flick assay. The antinociception induced by DSC at the dose of 30 microg
      reached at peak 7.5 min and almost returned to the control level after 60 min. 5
      Amino-valeric acid (5-AVA, a GABA(A) receptor antagonist, from 1 to 20 microg)
      and SR 95531 (a GABA(B) receptor antagonist, from 0.1 to 2 ng) dose-dependently
      attenuated i.t. administered DSC-induced increase of the inhibition of the tail
      flick response. The i.t. injection of yohimbine (an alpha(2)-adrenergic receptor
      antagonist, from 1 to 20 microg) and methysergide (a serotonin receptor
      antagonist, from 1 to 20 microg), but not naloxone (from 2 to 8 microg),
      significantly attenuated inhibition of the tail-flick response induced by DSC (30
      microg) administered i.t. Sulfated cholecystokinin (CCK, from 0.05 to 0.5 ng)
      injected i.t. significantly reduced the inhibition of the tail-flick response
      induced by DSC (30 microg) administered i.t. Our results suggest that DSC shows
      an antinociceptive effect when it is administered spinally and GABA(A), GABA(B),
      alpha(2)-adrenergic and serotonin receptors located at the spinal cord level, but
      not opioid receptors, may be involved in DSC-induced antinociception.
      Furthermore, CCK may play an important role for the modulation of i. t. injected
      DSC-induced antinociception.

PMID- 10904166
TI  - Analytical and pharmacological investigation of Ocotea bullata (black stinkwood)
      bark and leaves.
AB  - Ocotea bullata (Lauraceae), one of the top-ten traditional medicinal plants used
      in KwaZulu-Natal, is close to extinction through high demand and destructive
      harvesting methods. The stem bark is traditionally used to cure headaches,
      urinary disorders and stomach problems. Substitution of leaves for bark provides
      a possible resource management solution for this threatened medicinal plant. One
      aim of this study was to compare the chemical composition of O. bullata leaves
      and bark using TLC, HPLC and GC-MS analysis. The characteristic analytical
      fingerprints of leaf and bark extracts showed great similarities. A second aim
      was to investigate the pharmacological properties of O. bullata as a remedy
      against headaches. Leaf and bark extracts were tested in terms of cyclooxygenase
      1 and 5-lipoxygenase inhibition. Extracts from the bark exhibited moderate
      inhibitory activity in both test systems. Extracts from fresh leaves were
      superior to bark extracts in terms of their in vitro inhibitory activity against
      cyclooxygenase-1 and 5-lipoxygenase. Volatiles obtained from n-hexane extracts of
      leaves and bark showed better inhibitory activity towards cyclooxygenase-1 and
      especially towards 5-lipoxygenase than the original n-hexane extracts. Volatiles
      were therefore recognized as one of the main active principles in O. bullata with
      regards to the anti-inflammatory properties of this medicinal plant. This lends
      support to the traditional usage of O. bullata bark as an inhalant or snuff.

PMID- 10904167
TI  - Antifeedant and antifungal activity of chromene compounds isolated from
      Blepharispermum subsessile.
AB  - Desmethyl isoencecalin and 5-hydroxy-6-acetyl-2-hydroxymethyl-2-methyl chromene
      isolated from Blepharispermum subsessile rhizomes were shown to have antifeedant
      activity against larvae of Spilarctia obliqua and also antifungal activity
      against Candida albicans and Cryptococcus neoformans (MIC 25-250 microg/ml).

PMID- 10904168
TI  - Effect of Kombucha tea on chromate(VI)-induced oxidative stress in albino rats.
AB  - The effect of Kombucha tea (KT) on oxidative stress induced changes in rats
      subjected to chromate treatment are reported. KT feeding alone did not show any
      significant change in malondialdehyde (MDA) and reduced glutathione (GSH) levels,
      but did enhance humoral response and delayed type of hypersensitivity (DTH)
      response appreciably over control animals. Chromate treatment significantly
      enhanced plasma and tissue MDA levels, decreased DTH response considerably,
      enhanced glutathione peroxidase and catalase activities; however, no change in
      GSH, superoxide dismutase and antibody titres was noticed. KT feeding completely
      reversed the chromate-induced changes. These results show that Kombucha tea has
      potent anti-oxidant and immunopotentiating activities.

PMID- 10904169
TI  - Biologically active alkaloids and a free radical scavenger from Prosopis species.
AB  - The biological activity of extracts from the aerial parts of five Argentinian
      Prosopis species and the exudate of P. flexuosa were assessed for DNA binding,
      beta-glucosidase inhibition and free radical scavenging effect using the DPPH
      decoloration assay. DNA binding effect was found mainly in the basic fraction.
      The alkaloids tryptamine as well as piperidine and phenethylamine derivatives
      were isolated from the basic extracts. At 0.50 mg/ml, DNA binding activities
      ranged from 28% for tryptamine to 0-27% for the phenethylamine and 47-54% for the
      piperidine derivatives. Tryptamine and 2-beta-methyl-3-beta-hydroxy-6-beta
      piperidinedodecanol showed a moderate inhibition (27-32%) of the enzyme beta
      glucosidase at 100 microg/ml. The exudate of P. flexuosa displayed a strong free
      radical scavenger effect in the DPPH decoloration assay. The main active
      constituent was identified as catechin.

PMID- 10904170
TI  - Fasciolicidal efficacy of Albizia anthelmintica and Balanites aegyptiaca compared
      with albendazole.
AB  - An attempt was made to evaluate the oral doses of 9 g/kg-body weight of Albizzia
      anthelmintica Brong. Mimoaseae stem bark water extract and 9 g/kg body weight of
      B. aegyptiaca (L) Del. (Balanitaceae) fruit mesocarp water extract (traditionally
      used as an anthelmintic in the Sudan) compared with 20 mg/kg body weight
      (recommended dose) of albendazole against Fasciola gigantica adult worm (12 weeks
      old) in five groups each of three goats (6 month old). Group (I) uninfected
      control, group (II) infected untreated control, group (III, IV and V) infected
      and treated as mentioned above respectively. Based on the percentage reduction in
      fluke counts from the liver post mortum 2 weeks after treatment, the efficacy of
      the mentioned therapeutics was 95.5, 93.2 and 97.7%, respectively. The
      characteristic lesions of liver fasciolosis, egg/gm of faeces (EPG), packed cell
      volume (PCV), haemoglobin concentration, total red blood cells count (RBC), total
      white blood cells count (WBC) and oesinophil% were significantly different from
      control and treated groups (P<0.05).

PMID- 10904171
TI  - Possible involvement of cholinergic and adrenergic mechanisms in changing
      contractility of guinea pig ileum by Ipomoea carnea.
AB  - The study aimed to elucidate the mechanism (s) of action of Ipomoea carnea leaf
      juice (ILJ) in changing contractility of guinea pig ileum. ILJ produced dose
      dependent (10-10000 microg/ml) triphasic responses. The initial contractile phase
      was blocked by atropine (1 microg/ml) but had additive effect with acetylcholine
      (2 ng/ml) or carbachol (2 ng/ml). Neostigmine (30 ng/ml) or lignocaine (50
      microg/ml) failed to alter the response. In cold-induced denervated preparations,
      this phase was augmented. The relaxatory phase of ILJ was not modified by
      phenoxybenzamine (35 microg/ml) but was reduced by propranolol (1 microg/ml) and
      abolished by lignocaine (50 microg/ml). The final contractile phase of ILJ was
      not affected by atropine (1 microg/ml). These results suggest that the triphasic
      response of ILJ is possibly mediated through cholinergic, adrenergic and non
      cholinergic mechanisms, respectively.

PMID- 10904172
TI  - Effect of Picrorrhiza kurroa extract on transplanted tumours and chemical
      carcinogenesis in mice.
AB  - Anti-tumour and anti-carcinogenic activity of Picrorrhiza kurroa extract were
      studied in mice. Administration of 20-methylcholanthrene (20 MC) produced 100%
      induction of sarcoma in control mice, whereas the tumour incidence and tumour
      related deaths were significantly inhibited by the oral administration of P.
      kurroa extract 150 and 750 mg/kg body weight, respectively. The extract was also
      found to reduce the volume of transplanted solid tumours induced by Dalton's
      lymphoma ascites (DLA) tumour cell lines and increased the life span of ascites
      tumour bearing mice. P. kurroa extract inhibited yeast topoisomerase I and II
      enzyme activity when tested on Saccharomyces cerevisiae mutant cell cultures. The
      extract did not inhibit the enzyme involved in the activation of carcinogen and
      the cell cycle regulatory enzyme cdc2 kinase.

PMID- 10904173
TI  - The juice of fresh leaves of Boerhaavia diffusa L. (Nyctaginaceae) markedly
      reduces pain in mice.
AB  - The decoction or juice of leaves of Boerhaavia diffusa L. (Nyctaginaceae) is used
      in Martinican folk medicine for its analgesic and anti-inflammatory properties.
      In the present investigation we studied the acute oral (p.o.) toxicity of a crude
      extract obtained from a lyophilized decoction (DE) and from the juice (JE) of
      fresh leaves. We observed no signs of toxicity up to the dose of 5000 mg/kg
      (p.o.) in mice. At the dose of 1000 mg/kg, neither extract altered sleeping time
      evoked by the administration of pentobarbital sodium (i.p.). The DE and JE of B.
      diffusa were assessed in standard rodent models of algesia and inflammation. We
      investigated the antinociceptive effect of DE and JE in chemical (acetic acid)
      and thermal (hot plate) models of hyperalgesia in mice. Dipyrone sodium (200
      mg/kg), JE (1000 mg/kg) and DE at the same dose (p.o.), produced a significant
      inhibition of acetic acid-induced abdominal writhing in mice (100, 50 and 47%
      inhibition, respectively) when compared with the negative control (P<0.001). In
      the hot-plate test in mice, morphine and JE produced a significant increase in
      latency during the observation time. The DE, however, only raised the pain
      thresholds during the first period (30 min) of observation (P<0.05). The extracts
      of B. diffusa were also investigated for their anti-edematogenic effect on
      carrageenan-induced edema in mice. However, neither extract inhibited the paw
      edema induced in mice (P>0.05). In the acetic acid-induced abdominal writhing in
      mice, pre-treatment of the animals with naloxone (5 mg/kg, i.p.) significantly
      reversed the analgesic effect of morphine and JE but not that of DE. These data
      show that the active antinociceptive principle of B. diffusa is present mainly in
      the juice of fresh leaves and has a significant antinociceptive effect when
      assessed in these pain models. The mechanism underlying this analgesic effect of
      fresh leaves of B. diffusa remains unknown, but seems to be related to
      interaction with the opioid system.

PMID- 10904174
TI  - Antiplasmodial, analgesic, and anti-inflammatory activities of the aqueous
      extract of the stem bark of Erythrina senegalensis.
AB  - The in vivo antiplasmodial, analgesic and anti-inflammatory properties of
      Erythrina senegalensis, an ornamental plant commonly used in Northern Nigeria for
      the treatment of fevers, was evaluated. Aqueous extracts of the stem bark of the
      plant was used for the study. The in vivo antiplasmodial activity of the aqueous
      extract against Plasmodium berghei was assessed using the suppressive and
      curative test procedures. Analgesic activity was assessed using the acetic acid
      (0.75%v/v) induced abdominal constriction, while the anti-inflammatory activity
      was evaluated on egg-albumin induced paw oedema in rats as a model of acute
      inflammation. The stem bark extract of E. senegalensis exhibited only slight
      antiplasmodial activity while significant (P<0.05) analgesic and anti
      inflammatory effects were observed. Preliminary phytochemical analysis of the
      extract indicates the presence of alkaloids and glycosides.

PMID- 10904176
TI  - Anti-inflammatory activities of Trichilia glabra aqueous leaf extract.
AB  - Trichilia glabra L. aqueous leaf extract exerted a significant antiinflammatory
      effect 'in vivo' in the zymosan-induced inflammation model. The extract impaired
      the 'in vitro' activities of polymorphonuclear leukocytes and complement,
      components of mouse immune system closely related to the inflammatory response
      induced by zymosan. In particular, a significant reduction in the phagocytic
      capability and respiratory burst response of mouse polymorphonuclear leukocytes
      together with an inhibition in the hemolytic activity of mouse complement was
      observed.

PMID- 10904175
TI  - Plant part substitution--a way to conserve endangered medicinal plants?
AB  - Population growth, urbanization and the unrestricted collection of medicinal
      plants from the wild is resulting in an over-exploitation of natural resources in
      southern Africa. Therefore, the management of traditional medicinal plant
      resources has become a matter of urgency. In southern Africa the most frequently
      used medicinal plants are slow-growing forest trees, bulbous and tuberous plants,
      with bark and underground parts being the parts mainly utilized. A strategy which
      would satisfy the requirements of sustainable harvesting, yet simultaneously
      provide for primary health care needs, would be the substitution of bark or
      underground parts with leaves of the same plant. This paper outlines the concept
      of plant substitution, using preliminary results of our recent investigations
      into four of the most important and most threatened South African medicinal
      plants - Eucomis autumnalis (bulb), Siphonochilus aethiopicus (rhizome), Ocotea
      bullata (bark), and Warburgia salutaris (bark) - as a demonstration of the kind
      of research necessary. Extracts of various plant parts were compared chemically
      using TLC-analysis, and pharmacologically in terms of antibacterial activity and
      cyclooxygenase-1 inhibition in vitro. The importance of the concept of plant part
      substitution as a strategy for the conservation of medicinal plants in southern
      Africa is discussed in terms of the results obtained.

PMID- 10904177
TI  - Suppression of croton oil-induced rabbit corneal edema by sideritis
      javalambrensis.
AB  - This investigation was designed to evaluate the anti-inflammatory activity of the
      aqueous and hexane extracts of Sideritis javalambrensis, to which pharmacological
      properties have been attributed in Spanish traditional medicine. The extracts
      were applied as eye drops in a croton oil-induced corneal edema model in rabbits.
      Corneal thickness was estimated before the induction of inflammation and 3, 6, 8,
      12, 48, 72 and 96 h after induction. Significant inflammation inhibition
      percentages were shown during both the acute and chronic stages of inflammation
      by both extracts and by the reference drug dexamethasone, with most therapeutic
      effect shown during the chronic phase. However, the hexane extract exhibited
      potent anti-inflammatory activity from 6 to 24 h post-induction, achieving
      greater percentage inhibition values during this stage than those obtained for
      dexamethasone.

PMID- 10904178
TI  - Antimicrobial activity of bark extracts of Syzygium jambos (L.) alston
      (Myrtaceae).
AB  - Syzygium jambos (L.) Alston (Myrtaceae) is a widespread medicinal plant
      traditionally used in sub-Saharan Africa to treat infectious diseases. Acetone
      and aqueous extracts from the bark of S. jambos were tested for antimicrobial
      activity in vitro by the agar dilution method in petri dishes. Both extracts
      showed some activity against the tested micro-organisms. They proved to be
      particularly effective on Staphylococcus aureus, Yersinia enterocolitica and
      coagulase negative staphylococci among which Staphylococcus hominis,
      Staphylococcus cohnii and Staphylococcus warneri. These properties seem to be
      related to the high tannin content of S. jambos extracts (77 and 83% for the
      aqueous and acetone extracts, respectively, determined according to the European
      Pharmacopoeia method) which were generally more active than Hamamelis virginiana,
      Krameria triandra, Alchemilla vulgaris and Rubus fruticosus extracts containing
      48, 44, 46 and 28% tannins, respectively. Furthermore, elimination of tannins
      totally suppressed these antimicrobial activities.

PMID- 10904179
TI  - Gastric anti-secretory and anti-ulcerogenic effects of Dombeya buettneri in rats.
AB  - The effects of an aqueous extract of the leaves of Dombeya buettneri on gastric
      acid secretion and ethanol-induced gastric mucosal damage were studied in rats.
      Gastric acid secretion was measured by continuous perfusion in urethane
      anaesthetised rats. Intragastric perfusion with the extract caused significant
      reduction in basal and histamine-stimulated gastric acid secretion. Pretreatment
      with the extract also reduced the extent of gastric mucosal damage induced by
      oral ethanol (75% v/v), but had no effect on mucus secretion. It is suggested
      that the consumption of an extract of the leaves of D. buettneri may be
      beneficial in the prevention and treatment of peptic ulcer disease.

PMID- 10904181
TI  - The hypoglycaemic and antihyperglycaemic effect of citrullus colocynthis fruit
      aqueous extract in normal and alloxan diabetic rabbits.
AB  - Effects of the aqueous, glycosidic, alkaloidal and saponin extracts of the rind
      of Citrullus colocynthis on the plasma glucose levels were investigated in normal
      rabbits, while the effects of saponin extract on the fasting plasma glucose
      levels were studied in alloxan induced diabetic rabbits. In normal rabbits, oral
      administration of aqueous extract (300 mg/kg) produced significant reduction in
      plasma glucose after 1 h and highly significant after 2,3 and 6 h. Phytochemical
      screening revealed that the rind of C. colocynthis and its aqueous extract
      contains tertiary and quaternary alkaloids, glycoside and saponin components. The
      hypoglycaemic effects of these components given orally at a dose (50 mg/kg) were
      studied in normoglycaemic rabbits. Result showed that the alkaloidal extract did
      not significantly lower the blood glucose levels from 132 mg/100 ml at 0 h to 120
      mg/100 ml after 6 h, while the glycosidic extract significantly lowered the
      fasting glucose levels after 2 and 3 h and highly significant after 6 h. The
      effect was more pronounced with saponin extract, the saponin significantly
      lowered the fasting glucose levels after 1 and 2 h and highly significant
      (P<0.001) after 3 and 6 h. Graded doses (10, 15 and 20 mg/kg) of saponin extract,
      when given orally to alloxan diabetic rabbits, produced a significant reduction
      of plasma glucose concentration. These results suggest that the aqueous extract
      of the rind of C. colocynthis possesses a hypoglycaemic effect and its
      hypoglycaemic action could be attributed for more extent to the presence of
      saponin in addition to the presence of glycosidic components.

PMID- 10904180
TI  - Sedative activity of two flavonol glycosides isolated from the flowers of
      Albizzia julibrissin Durazz.
AB  - The flowers of Albizzia julibrissin are used as a sedative in oriental
      traditional medicine. The phytochemical study of this plant allowed the isolation
      of two flavonol glycosides, quercitrin (1) and isoquercitrin (2). The sedative
      activity of these compounds was evaluated, and both compounds 1 and 2 increased
      pentobarbital-induced sleeping time in dose-dependent manner in mice. These
      results support the use of the flowers of this plant as a sedative agent.

PMID- 10904183
TI  - The use of complex polysaccharides in the management of metabolic diseases: the
      case of Solanum lycocarpum fruits.
AB  - In the Brazilian cerrado, a preparation obtained from the fruits of Solanum
      lycocarpum St.-Hil. (Solanaceae), popularly known as 'fruta-de-lobo' (wolf
      fruit), have been widely employed for diabetes management, obesity and to
      decrease cholesterol levels. The medicinal preparation consists of the green
      fruits which are ground in aqueous solution and filtered. The white 'gum'
      deposited is decanted and slowly dried providing a powder which is commercialized
      in capsules with the name of 'polvilho-de-lobeira'. Through phytochemical
      analysis of this phytomedicine and the fruit of S. lycocarpum we found
      polysaccharides as the main component. Some polysaccharides slow gastric emptying
      and act on the endocrinous system affecting the liberation of gastrointestinal
      hormones, lowering blood glucose levels. The hypocholesterolemic activity could
      be due to the increased fecal bile acid excretion as well as to the action of the
      short-chain fatty acids, coming from fermentation, on the synthesis of delta
      aminolevulinate and by the increase of the cholesterol 7-alpha-hydroxylase and 3
      hydroxy-3-methylglutaryl CoA reductase synthesis.

PMID- 10904182
TI  - Evaluation of the pharmacological activity of extracts from amomi semen on the
      gastrointestinal tracts.
AB  - We have investigated the effects of methanolic and alcoholic extracts from Amomi
      Semen on gastric secretion, as well as gastrointestinal propulsion or the
      prokinetic activities. The methanolic extract from Amomi Semen dose dependently
      decreased the volume output, acid output, and pepsin output in rat's gastric
      juice with increasing pH value, while the alcoholic extract had no influence on
      basal gastric acid secretion. Furthermore, the alcoholic extract improved the L
      dopa to induce a delay of gastrointestinal transit in mice, while the methanolic
      extract did not improve it. However, both extracts had no influence on
      gastrointestinal transit in intact mice. These results suggest that Amomi Semen
      has an inhibitory effect on gastric acid secretion and that it has effects as the
      gastrointestinal prokinetics rather than propulsion. The present study
      pharmacologically elucidates a belief that Amomi Semen has been used in Chinese
      medicine for the treatment of gastrointestinal dyspepsia, which includes
      hyperchlorhydria, stomachache, abdominal distention, anorexia, gastric atony,
      etc.

PMID- 10904184
TI  - Absence of antihyperglycemic effect of jambolan in experimental and clinical
      models.
AB  - The use of alternative therapies to treat diabetes, including teas prepared with
      different vegetables, is widespread in Brazil. In Porto Alegre, a southern city
      of Brazil, the tea prepared from leaves of Syzygium cumini (L.) Skeels or S.
      jambos (L.) Alst has been report to be used frequently by diabetic patients. We
      investigated the postulated antihyperglycemic effect of the S. cumini (L.) Skeels
      in three experiments. In the first, a randomized, parallel, placebo controlled
      trial, tea prepared from leaves of S. cumini did not present any
      antihyperglycernic effect in 30 non-diabetic young volunteers submitted to a
      glucose blood tolerance test. In the animal experiments, we tested the effect of
      increasing doses of the crude extract prepared from leaves of S. cumini
      administrated for 2 weeks, on the post-prandial blood glucose level of normal
      rats and rats with streptozotocin-induced diabetes mellitus. The treatment did
      not produce any antihyperglycernic effect in both models. These results do not
      rule out hypoglycemic effects in patients with type 2 diabetes mellitus, but
      strongly suggest that, for a while, the jambolan can not be recommended as an
      antihyperglycemic treatment.

PMID- 10904185
TI  - Effect of methanolic extract of Enicostemma littorale on Dalton's ascitic
      lymphoma.
AB  - The antitumour activity of methanolic extract of Enicostemma littorale (MEL) has
      been evaluated against Dalton's ascitic lymphoma (DAL) in swiss albino mice. A
      significant enhancement of mean survival time of MEL treated tumour bearing mice
      was found with respect to control group. MEL treatment was found to enhance
      peritoneal cell counts. When these MEL treated animals underwent i.p. inoculation
      with DAL cells, tumour cell growth was found to be inhibited. After 14 days of
      inoculation, MEL is able to reverse the changes in the haemotological parameters,
      protein and PCV consequent to tumour inoculation.

PMID- 10904186
TI  - Evaluation of the BIOMIC video reader system for routine use in the clinical
      microbiology laboratory.
AB  - The BIOMIC Video Reader System (Giles Scientific, New York, NY, USA) is a semi
      automated AST method that combines disk diffusion testing with automated reading
      and data interpretation. We evaluated this system with 497 strains comprising a
      total of 5821 drug organism combinations (DOC) from our routine diagnostic
      laboratory. Additionally, we compared the time required of the manual and the
      automated method. The overall agreement of interpretative categories of all DOC
      was 96.1%. However, comparing complete tests the agreement was only 70.8%. The
      average time required of the BIOMIC system to complete a test was more than twice
      as long as that of the manual method. Our data suggest that the tested version of
      the BIOMIC system cannot be recommended for routine use in diagnostic
      laboratories.

PMID- 10904187
TI  - Evaluation of the Bio-Rad syphilis IgG test performed on the CODA system for
      serologic diagnosis of syphilis.
AB  - The performance of the Bio-Rad Syphilis IgG EIA test as a "screen for syphilis"
      [testing first by EIA and then by the rapid plasma reagin (RPR) assay if the EIA
      was positive or equivocal] and as a confirmatory test was evaluated by comparing
      results to those obtained by CAPTIA Syphilis-G. Discrepancies were resolved by
      repeating both EIAs and/or the SeroDia TP-PA (a particle agglutination assay that
      replaced the microhemagglutination Treponema pallidum test). Both EIAs were
      totally automated, the Bio-Rad test using the AutoPrep instrument for pipetting
      and the CODA system to perform all of the steps required to complete the EIA and
      interpret results, and the CAPTIA test using the LabOTech(R) to accomplish both
      functions. Of 449 unselected sera submitted to "screen for syphilis," both EIAs
      agreed for 432 (96.2%) specimens: 395 negative, 36 positive, and one equivocal.
      Fifty-four specimens were positive or equivocal by one or both EIAs; 41 of these
      were RPR reactive. Three of these 41 were incorrectly called negative by Bio-Rad
      (sensitivity 92.7%), and there was 1 false-negative result by CAPTIA
      (sensitivity, 97.6%) (P, not significant). To further evaluate the Bio-Rad assay
      as a confirmatory test, 144 known RPR-reactive specimens were tested by both
      EIAs. Results agreed for 134 (93.1%): 123 positive, 11 negative. After resolving
      discrepancies, there were 3 false-negative and no false-positive results by Bio
      Rad (sensitivity 97.8%, specificity 100%), and with CAPTIA there were no false
      negative results and 1 false-positive (sensitivity 100%, specificity 91.7%) (P,
      not significant). The sensitivity of the Bio-Rad assay could be improved, without
      altering specificity, by lowering the cut-off value for equivocal results. In
      summary, the Bio-Rad Syphilis IgG EIA performed using the AutoPrep instrument and
      CODA system is a reliable, efficient method of syphilis testing.

PMID- 10904188
TI  - Search for Pneumocystis carinii DNA in upper and lower respiratory tract of
      humans.
AB  - Recent studies suggest that Pneumocystis carinii DNA may be detected by PCR in
      oropharyngeal secretions in the majority of patients with P. carinii pneumonitis
      (PCP). However, the prevalence of P. carinii DNA in patients without PCP has not
      been well established. A prospective study of 258 nasal, pharyngeal, and salivary
      specimens from 86 individuals with AIDS, cancer or no underlying disease, and
      without respiratory infection, found no P. carinii DNA in any of the samples.
      Separately, to validate the PCR for detection of P. carinii DNA, 45 specimens
      from the lower respiratory tract (bronchoalveolar lavage [BAL] and sputum) from
      31 patients with pneumonitis and AIDS or cancer were studied. Eleven had PCP by
      conventional stains and 20 did not. All patients with PCP, and none without PCP,
      had P. carinii DNA in BAL, sputum or both. The study indicates the prevalence of
      P. carinii DNA is low or absent in oropharyngeal secretions in the absence of
      PCP.

PMID- 10904189
TI  - Evaluation of a water-extracted pharmamedia agar medium for the culture of fungi.
AB  - The purpose of this investigation was to determine the value of a water-extracted
      Pharmamedia agar medium for the culture of fungi. The growth of the fungi on this
      medium was compared to that on Sabouraud brain heart infusion agar. The
      Pharmamedia extract agar supported the growth of the 42 filamentous and yeast or
      yeast-like fungi that were examined. The medium was relatively clear to easily
      permit observation of the diagnostic microscopic and macroscopic architecture of
      the organisms. The Pharmamedia extract agar also permitted the conversion of the
      mold-to-yeast phase with Blastomyces dermatitides and Penicillium marneffei. This
      investigation supports the use of Pharmamedia as a culture medium for the
      clinical microbiology laboratory. Its relative simplicity of preparation and
      effective use as a culture medium, as well as a conversion medium, emphasizes its
      useful application for clinical mycology.

PMID- 10904190
TI  - The central nervous system and infection by Candida species.
AB  - In this paper we have reviewed the main clinico-pathologic disease groups of
      neurocandidiasis: the microabscesses, the macroabscesses, and the meningitis.
      Special attention has been paid to the predisposing conditions for the appearance
      of neurocandidiasis, the neuroimaging techniques, and the study of the
      cerebrospinal fluid, needed for diagnosis. We have also discussed the
      differential diagnosis with other illnesses. Treatment should be given with
      amphotericin-B and 5-fluorocytosine. The use of other antifungal drugs for
      neurocandidiasis is also discussed.

PMID- 10904191
TI  - Detection of Chlamydia trachomatis in symptomatic and asymptomatic populations
      with urogenital specimens by AMP CT (Gen-probe incorporated) compared to others
      commercially available amplification assays.
AB  - The present study was designed to evaluate the sensitivity and specificity of AMP
      CT (Gen-Probe Incorporated, San Diego, CA, USA) on urogenital specimens taken
      from symptomatic patients and on first void urine (FVU) specimens from
      asymptomatic patients. In symptomatic patients, 618 specimens from 140 men (140
      urethral swabs and 140 FVU) and 202 women (202 endocervical swabs and 136 FVU)
      were tested by using cell culture, AMP CT and Amplicor Chlamydia trachomatis MWP
      (microwell plate) (Roche Diagnostics, Somerville, NJ, USA) on genital samples,
      and AMP CT and Amplicor on FVU. A clinical specimen was considered to be truly
      positive if either the cell culture was positive and/or both AMP CT and Amplicor
      were positive. In the asymptomatic population, a total of 300 FVU (136 women and
      164 men) were tested by four amplification methods, AMP CT, LCx (Abbott, Abbott
      Park, IL, USA), Amplicor MWP, and Cobas Amplicor. A subject was considered to be
      infected when two or more amplification methods were positive. In the symptomatic
      population (prevalence 13%), concordant results were observed in 320/342 cases
      (93.5%). After analysis of discordant results, the sensitivity of AMP CT,
      Amplicor, and culture was 100%, 95.5%, 68.8%, respectively, and the specificity
      was 98.3%, 99.3%, 100% respectively. The number of false negative results by AMP
      CT in urine, probably due to labile inhibitors, was 3/276 (1%). In the
      asymptomatic population, the results were concordant in 298/300 (99.3%), seven
      positive and 291 negative. Two results were considered false positives, one by
      Cobas Amplicor, one by AMP CT. Compared to other amplification methods, AMP CT is
      at least as sensitive for the identification of chlamydial infection in
      symptomatic and asymptomatic men and women on genital or urine specimens.

PMID- 10904192
TI  - In vitro study of the post-antibiotic effect and the bactericidal activity of
      Cefditoren and ten other oral antimicrobial agents against upper and lower
      respiratory tract pathogens.
AB  - The in vitro post-antibiotic effect (PAE) and batericidal activity of cefditoren
      was compared to that of cefixime, cefuroxime, loracarbef, cefaclor, amoxicillin,
      amoxicillin/clavulanate, clarithromycin, azithromycin, erythromycin, and
      ciprofloxacin against ATCC culture strains and clinical respiratory isolates. A
      PAE > 1 h was observed for cefditoren and generally for the macrolides against
      Streptococcus pneumoniae, beta-lactamase-negative Moraxella catarrhalis, and
      Streptococcus pyogenes, whereas the other beta-lactams showed mixed results.
      Cefditoren was the only beta-lactam showing significant bactericidal activity (>3
      log reduction of viable cells) within 4 h against penicillin-resistant S.
      pneumoniae. Only cefditoren and ciprofloxacin showed significant bactericidal
      activity against beta-lactamase-negative (after 24 h) and beta-lactamase-positive
      strains of H. influenzae (after 12 h). Against beta-lactamase-positive strains of
      M. catarrhalis, cefditoren was the only agent to show significant bactericidal
      activity at 6 h (versus cefuroxime and ciprofloxacin at 12 h).

PMID- 10904193
TI  - Development of gemifloxacin in vitro susceptibility test methods for gonococci
      including quality control guidelines. The Quality Control Study Group.
AB  - Gemifloxacin (formerly SB-265805 or LB20304a) is a new fluoronapthyridone with
      documented activity against Gram-positive and -negative organisms. The activity
      of gemifloxacin was tested against 150 Neisseria gonorrhoeae strains, using
      reference agar dilution, standardized disk diffusion, and Etest (AB BIODISK,
      Solna, Sweden) methods. Gemifloxacin was very potent against ciprofloxacin
      (CIPRO)-susceptible strains (MIC(90,) 0.008 microg/ml) but was significantly less
      active against the CIPRO-resistant gonococci (MIC(90,) 0.12 microg/ml). Etest and
      reference agar dilution MIC results showed excellent correlation (r = 0.96), and
      98.7% MICs were within +/- one log(2) dilution. Agar dilution MICs were also
      compared to zone diameters obtained using gemifloxacin 5-microg disks; and
      complete intermethod categorical agreement (100%) was achieved applying
      breakpoints proposed as follows: < or =0.25 microg/ml (zone, > or =25 mm) for
      susceptible and > or =1 microg/ml (zone, < or =21 mm) for resistant. Gemifloxacin
      MIC and disk diffusion te quality control (QC) ranges were established for N.
      gonorrhoeae ATCC 49226. Data were collected from > or = seven laboratories, three
      GC agar medium lots for both agar MICs and disk methods, and two lots each of the
      5- and 10-microg disks. The proposed MIC QC range was 0.002 to 0.016 microg/ml
      and the calculated mm zone ranges (median +/- 0.5x average mm range) for both
      disks were similar, but contained only 88.1 to 91.9% of participant results. To
      achieve the acceptable > or = 95% of all study results within range, a 43 to 54
      mm limits (5-microg disks) were necessary. The excellent broad-spectrum activity
      and a low reported adverse effects profile of gemifloxacin shows a potential for
      treatment of fluoroquinolone-resistant gonorrhea.

PMID- 10904195
TI  - Splenic abscesses caused by Actinomyces meyeri in a patient with autoimmune
      hepatitis.
AB  - We report a case of actinomycosis with uncommon localizations that was due to
      Actinomyces meyeri. Although penicillin is the standard treatment for this
      condition, our patient was treated successfully with imipenem. Actinomyces
      organisms are important constituents of the normal flora of mucous membranes and
      are considered opportunistic pathogens; these organisms may produce infection
      after local trauma, surgery, or aspiration. The mains forms of actinomycosis are
      cervicofacial, thoracic, and abdominal; most cases are due to Actinomyces
      israelii, whereas other Actinomyces species are occasionally implicated.
      Actinomycosis usually occurs in immunocompetent persons, but may occur in persons
      with diminished host defenses.

PMID- 10904194
TI  - Benchmarking the in vitro activity of moxifloxacin against recent isolates of
      Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. A
      European multi-centre study.
AB  - To benchmark the activity of moxifloxacin, a European study comprising 900
      Streptococcus pneumoniae, 1051 Haemophilus influenzae, and 226 Moraxella
      catarrhalis referred from 30 institutions during 1998 is described. For S.
      pneumoniae, moxifloxacin and trovafloxacin MIC(90) and modal MICs values were
      0.12 microg/ml and independent of susceptibility to other drug classes,
      geography, or site of infection. MIC(90)/modal MICs were, respectively, 0.25/0.12
      microg/ml for grepafloxacin, 0.25/0.25 microg/ml for sparfloxacin, and 1.0/0.5
      microg/ml for levofloxacin. The moxifloxacin C(max):MIC ratio of 20.8-26.3 is
      higher than comparator fluoroquinolones. Five isolates were intermediate or
      resistant to grepafloxacin, sparfloxacin, or levofloxacin of which four and three
      remained susceptible to trovafloxacin and moxifloxacin, respectively. For
      moxifloxacin, > 90% of S. pneumoniae isolates demonstrated MICs > or =3 dilutions
      below the susceptibility breakpoint used. Modal MICs and MIC(90) for M.
      catarrhalis (both 0.03 microg/ml) and H. influenzae (0.03 microg/ml and 0.06
      microg/ml) were independent of beta-lactamase production. These data demonstrate
      the in vitro activity of moxifloxacin and establish a baseline for future
      surveillance studies that will be important for detecting and tracking any trends
      in changing activity of this fluoroquinolone.

PMID- 10904196
TI  - Corneal perforation due to Acinetobacter junii: a case report.
AB  - Acinetobacter spp. is emerging as a common cause of nosocomial infections.
      Community acquired ocular infections due to Acinetobacter are rare. Only one case
      of perforation of cornea has been reported previously, where old nomenclature was
      used to describe the causal agent. We report a case of corneal perforation due to
      Acinetobacter junii for which a therapeutic penetrating keratoplasty was
      conducted and the patient eventually recovered.

PMID- 10904198
TI  - Introduction to the special supplement of the journal of adolescent health. Youth
      and media

PMID- 10904197
TI  - A community pseudo-outbreak of invasive Staphylococcus aureus infection.
AB  - Outbreaks of invasive infection caused by methicillin-susceptible and methicillin
      resistant Staphylococcus aureus occur in hospitals, long term care institutions,
      and in patients discharged from these settings. In contrast, epidemic S. aureus
      infection has not been reported in well persons in the community. Here, we
      describe a group of healthy young adults who resided in the same neighborhood and
      participated together in school sports, and who developed serious S. aureus
      infections within 3 weeks of each other, suggesting a true community outbreak.
      Timely use of molecular epidemiological tools, however, demonstrated that their
      illnesses were caused by unrelated bacterial strains.

PMID- 10904199
TI  - An agenda for research on youth and the media.

PMID- 10904200
TI  - Media and youth: access, exposure, and privatization.
AB  - PURPOSE: To describe U.S. youth's access and exposure to the full array of media,
      as well as the social contexts in which media exposure occurs. METHODS: A cross
      sectional national random sample of 2065 adolescents aged 8 through 18 years,
      including oversamples of African-American and Hispanic youth, completed
      questionnaires about use of television, videotapes, movies, computers, video
      games, radio, compact discs, tape players, books, newspapers, and magazines.
      RESULTS: U.S. youngsters are immersed in media. Most households contain most
      media (computers and video game systems are the exception); the majority of youth
      have their own personal media. The average youth devotes 6 3/4 h to media;
      simultaneous use of multiple media increases exposure to 8 h of media messages
      daily. Overall, media exposure and exposure to individual media vary as a
      function of age, gender, race/ethnicity, and family socioeconomic level.
      Television remains the dominant medium. About one-half of the youth sampled uses
      a computer daily. A substantial proportion of children's and adolescents' media
      use occurs in the absence of parents. CONCLUSIONS: American youth devote more
      time to media than to any other waking activity, as much as one-third of each
      day. This demands increased parental attention and research into the effects of
      such extensive exposure.

PMID- 10904201
TI  - Adolescents' media use: a European view.
AB  - European adolescents' use of mass media differs significantly by gender, family
      life, social economic status, and education, according to recent studies. For
      example, boys are more likely than girls to have a television in their own room,
      and content preferences are dramatically different. Recent studies also suggest
      that family dynamics may change as new media technologies are introduced. In some
      studies, the mother's educational status has been more directly related to
      patterns of electronic media use than the father's, and adolescents' commitment
      to school has been shown to predict music preferences. To make meaningful
      generalizations about adolescents and the media in the future, these and other
      mediating factors, including ethnicity and cognitive development, must be
      considered.

PMID- 10904202
TI  - New media technology and youth: trends in the evolution of new media.
AB  - An information environment is emerging from the simultaneous, rapid, and
      interconnected evolution of transmission systems, interfaces, and content
      quantity, quality, and structure. It will be easy to underestimate the collective
      impact of the sum of these changes on how young people communicate and absorb
      information. Ultimately, it will be more important to understand how these
      technologies will facilitate, amplify, or alter the cognitive processes and/or
      social behavior of the Internet generation. The article analyzes the impact of
      the following trends on media use and cognition among youthful users: *
      Information expansion and overload: Accessible networked information will
      continue to grow at a rapid pace for at least the next 10-20 years. * Rapid
      increase in interface diffusion: The number of access points into the Internet is
      expanding in number, variety, and mobility. * Evolution toward more embodied
      computing: Interfaces are evolving to use more of the sensorimotor system to
      transfer information to and from the user. * The evolution of more intelligent
      sensors to interpret use behavior and intentions. * Evolution toward
      anthropomorphic agent techniques: Computers are evolving to use more social and
      interpersonal communication techniques to interact with the user.

PMID- 10904203
TI  - Media violence.
AB  - Research on the effects of media violence is not well understood by the general
      public. Despite this fact, there is an overwhelming consensus in the scientific
      literature about the unhealthy effects of media violence. Meta-analyses show that
      media-violence viewing consistently is associated with higher levels of
      antisocial behavior, ranging from the trivial (imitative violence directed
      against toys) to the serious (criminal violence), with many consequential
      outcomes in between (acceptance of violence as a solution to problems, increased
      feelings of hostility, and the apparent delivery of painful stimulation to
      another person). Desensitization is another well-documented effect of viewing
      violence, which is observable in reduced arousal and emotional disturbance while
      witnessing violence, the reduced tendency to intervene in a fight, and less
      sympathy for the victims of violence. Although there is evidence that youth who
      are already violent are more likely to seek out violent entertainment, there is
      strong evidence that the relationship between violence viewing and antisocial
      behavior is bidirectional. There is growing evidence that media violence also
      engenders intense fear in children which often lasts days, months, and even
      years. The media's potential role in solutions to these problems is only
      beginning to be explored, in investigations examining the uses and effects of
      movie ratings, television ratings, and the V-chip, and the effects of media
      literacy programs and public education efforts. Future research should explore
      important individual differences in responses to media violence and effective
      ways to intervene in the negative effects.

PMID- 10904204
TI  - Adolescents' sexual media diets.
AB  - A model of how adolescents choose, interpret, and interact with the mass media is
      discussed in the context of sexual development. The Media Practice Model suggests
      that adolescents select and react to sexual media diets that speak to an emerging
      sense of themselves as sexual human beings. Relatively little is known about how
      the sexual content adolescents attend to in the media is interpreted or
      incorporated into their lives. Entertainment-education and media literacy are two
      strategies for increasing the possibility of healthy outcomes from adolescents'
      use of sexual media.

PMID- 10904205
TI  - Influence of unrestrained access to erotica on adolescents' and young adults'
      dispositions toward sexuality.
AB  - Because consensually accepted programs of sexual education are lacking, erotica
      have come to serve as the primary agent of sexual socialization. The new media
      technology gives prepubertal children and postpubertal adolescents ready access
      to erotica in all their manifestations. However, next to nothing is known about
      the consequences of the steadily increasing amount of such exposure. A brief
      overview of what is known and what remains unknown about the effects of
      pornography on young adults is presented. Thereafter, the focus is on the
      development of sexual callousness across the pubertal threshold, and on how this
      callousness might be influenced by extensive exposure to erotica. The erotica
      under consideration are not so much those explicitly depicting coital behaviors
      as those that are less explicit and present a fuller social context of sexual
      engagements. A program of research is outlined that would help provide an
      understanding of erotica's effects on adolescents' sexual callousness, an
      understanding that is sorely needed for the construction of effective educational
      efforts aiming at the removal of callousness and coercion from sexual relations.

PMID- 10904206
TI  - Media and civic socialization of youth.
AB  - Research on the development of citizenship has been reinvigorated by considering
      adolescents as participants actively engaged in, and interacting with, family,
      peers, teachers, and the media. This contrasts with earlier top-down transmission
      models that saw adolescents as passive recipients of information from parents and
      teachers. Active citizenship is now seen as a largely indirect result of
      contextualized knowledge and cognitive skills learned from news media use,
      interpersonal communication, and active participation in school and community
      volunteer activities. The processes of active citizenship learning are an
      important part of the moral development of adolescents and young adults.

PMID- 10904207
TI  - Media and youth consumerism.
AB  - Studies into the impact of advertising typically focus on three kinds of effects:
      cognitive, affective, and behavioral. This article summarizes research into types
      of effect and discusses the literature on several other predictors of children's
      consumer behavior, including age gender, socioeconomic level, and parent-child
      communication. The article ends with some information about European regulation
      about advertising and some suggestions for future research into children's
      consumer behavior.

PMID- 10904208
TI  - Multicultural media portrayals and the changing demographic landscape: the
      psychosocial impact of television representations on the adolescent of color.
AB  - The developmental stage of adolescence can be a challenging period with the need
      for the young person to negotiate certain early psychosocial and physiologic
      developmental tasks. The developmental tasks that are common to most adolescents
      can include some unique social, economic, and educational experiences for
      minority youth because of the sociocultural construction of American society.
      This article explores some of the theories, concepts, and creative issues related
      to the psychosocial impact on adolescents of color and multicultural portrayals
      that appear on television and in other emerging media.

PMID- 10904209
TI  - Youth and digital media: a policy research agenda.
AB  - At a time when researchers are still sorting out the complex relationship between
      adolescents and the mass media, the entire nature of the media system is
      undergoing dramatic change. The explosive growth of the Internet is ushering in a
      new digital media culture. Youth are embracing the new technologies much more
      rapidly than adults. In addition, because of their increased spending power,
      youth have become a valuable target market for advertisers. These trends have
      spurred the proliferation of Web sites and other forms of new-media content
      specifically designed for teens and children. The burgeoning digital marketplace
      has spawned a new generation of market research companies, and market research on
      children and youth is outpacing academic research on youth and the newer media.
      The emergence of this new media culture holds both promise and peril for youth.
      Whether the positive or negative vision of the digital future prevails will be
      determined, in large part, by decisions being made now and in the next few years
      in the halls of government and in corporate boardrooms. Research has contributed
      to the resolutions of several recent legislative and policy decisions in areas
      including television violence and the V-chip, children's educational television
      programming, and privacy and marketing to children on the Web. Future research
      needs to be designed with the public policy agenda in mind. The academic
      community has much to contribute to the debates over new developments in the
      digital age.

PMID- 10904210
TI  - The challenge of the evolving media environment.
AB  - As media become more powerful and prominent, questions about their positive and
      negative effects on children and youth will increase. Although the body of
      quality research about media and youth is growing, there are some significant
      gaps. Three important areas for future research are identified: physiological
      research, differential effects research, and media education outcomes research.

PMID- 10904211
TI  - Media matters for youth health.
AB  - We live in a media world and the mass media offer educational and entertainment
      opportunities for adults and children. However, pediatricians and parents are
      increasingly aware of the potential health risks that media exposure presents to
      children and adolescents. For many years, the American Academy of Pediatrics
      (AAP) has made media education a key goal for member pediatricians: Six policy
      statements about the impact of mass media have been published (and revised) over
      the past decade. In 1997, the AAP launched a 5-year, nationwide media education
      campaign called Media Matters. Although education about media is the cornerstone
      of Media Matters, pediatricians have other important roles. In offices and
      clinics, the AAP suggests that pediatricians take a media history from patients
      and discuss connections between a child's health and behavior and media use
      habits. Pediatricians can also provide anticipatory guidance to families about
      media in the home, including limiting media use, making wise media choices,
      encouraging co-viewing and critical thinking, and making the home a positive
      media environment. Many gaps in our knowledge about the effects of media images
      and messages on young people still exist; pediatricians call for ongoing,
      targeted research about media. In this way, we can all enjoy the benefits offered
      by media, while minimizing the risks.

PMID- 10904212
TI  - Periodic alternating nystagmus and vestibulo-spinal system facilitating activity.
AB  - OBJECTIVE: Periodic alternating nystagmus has been associated with the
      instability of the velocity storage mechanism, which is known to play an
      important role in both the vestibulo-oculomotor and the optokinetic systems. In
      the present study we looked for a possible spinal equivalent to PAN. METHODS AND
      RESULTS: In 3 PAN patients, the H-reflex amplitude proved to be slightly but
      significantly influenced by nystagmus direction, in that it was greater when the
      nystagmus was beating toward the stimulation side. CONCLUSIONS: This finding
      suggests that projections from velocity storage may play a role not only in the
      ocular motor but also in assisting postural stability through the vestibulo
      spinal system.

PMID- 10904214
TI  - Cortical motor reorganization following early brain damage and hemispherectomy
      demonstrated by transcranial magnetic stimulation.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) was utilized to study 7
      patients who had undergone hemispherectomy for control of longstanding
      intractable epilepsy to assess cortical motor reorganization and MEP (motor
      evoked potentials) ipsilateral to the remaining hemisphere. Five patients were
      seizure-free post-operatively. All patients displayed a spastic hemiparesis, were
      able to walk, raise and bend the paretic arm and use the paretic hand to
      different degrees. METHODS: We examined MEP threshold, site of maximal response
      to TMS, and latency to the biceps brachii, abductor pollicis brevis and the
      anterior tibial muscles using a 7 and 12 cm diameter round coil. RESULTS: The
      following results were obtained: (1) No MEP could be induced to either side by
      use of the small coil. (2) When using the large coil MEP-threshold was elevated
      also when stimulating the non-affected hemisphere in comparison to normal
      controls. (3) Ipsilateral MEP were found to: be non-inducible in two patients,
      demonstrate largely increased latencies in 3 and be identical to contralateral
      MEP in two patients. (4) Ipsilateral MEP could be evoked more often in distal
      than proximal muscles. (5) The site of maximal ipsilateral MEP response was found
      approximately 2 cm anteriorly to that of the contralateral MEP to the non
      affected side of the body (6) No correlation was found between the degree of
      hemiparesis and inducability of MEP. CONCLUSIONS: The pattern of reorganization
      of ipsilateral motor control following early brain damage and hemispherectomy
      appears to be extremely diverse and does not correlate with the degree of
      neurological impairment.

PMID- 10904213
TI  - Remote effects of cortical dysgenesis on the primary motor cortex: evidence from
      the silent period following transcranial magnetic stimulation.
AB  - OBJECTIVE: In cortical dysgenesis (CD), animal studies suggested abnormal cortico
      cortical connections. Cerebral areas projecting to the primary motor cortex (M1)
      modulate the cortical silent period (CSP) following transcranial magnetic
      stimulation (TMS). Therefore, we used the CSP to investigate remote effects of CD
      on the M1. METHODS: A detailed investigation, including single-pulse TMS and
      electrical nerve stimulation, was performed in 3 consecutive adults with focal CD
      located outside the M1 and in 18 controls. Two patients with unilateral CD were
      epileptic and treated with anti-epileptic drugs. One patient with focal CD on
      both sides had no history of seizures. Neurological examination was normal in all
      patients. Recordings were made from both first dorsal interosseous muscles.
      RESULTS: In CD patients, the CSP was significantly lengthened contralaterally to
      the affected hemispheres. In treated patients with unilateral CD, the interside
      difference of the CSP duration was also significantly increased. In contrast,
      excitability threshold, peripheral and corticospinal motor conduction studies,
      and peripheral as well as ipsilateral silent periods were not significantly
      modified. CONCLUSIONS: Our findings indicate that focal CD outside the M1 may
      produce CSP modifications, which are likely due to changes of afferent control.

PMID- 10904215
TI  - Classification of movement-related EEG in a memorized delay task experiment.
AB  - OBJECTIVES: We studied the activation of cortical motor areas during a memorized
      delay task with a classification technique. METHODS: Multichannel EEG was
      recorded during the sequence of warning stimulus, visual cue, reaction stimulus,
      and actual execution of hand or foot movements. Two different approaches are
      presented: first, we trained a classifier on data from the time segments
      immediately preceding the actual movements, and analyzed the whole recordings in
      overlapping segments with this fixed classifier. The classification rates
      obtained as a function of experimental time reflect the activation of the same
      cortical areas that are active during the actual movements. In the second
      approach, we trained classifiers on data segments with the same latency in time
      as the data tested ('running classifiers'). By this, we checked whether we could
      detect event-related activity sufficiently marked to allow for correct
      classification. RESULTS: With the fixed classifier approach we found two maxima
      of classification: one maximum after processing of the visual cue corresponding
      to an activation of motor cortex without overt movement, and a second maximum at
      the time of the actual movement. The first maximum relates to a very short-lived
      brain state, in the order of 300 ms, while the broad second maximum (1.5 s)
      indicates a very stable and long-lasting activation. CONCLUSIONS: With the
      running classifier approach we found similar maxima as with the fixed classifier,
      indicating that only the activity of motor areas is relevant for classification.
      Possible implications of our findings for the development of a brain computer
      interface (BCI) are discussed.

PMID- 10904216
TI  - Abnormalities of the acoustic startle reflex and reaction time in gilles de la
      tourette syndrome.
AB  - OBJECTIVE: To study the startle reflex and the effect of the startle reflex
      stimulus over reaction time (start-react effect) in Gilles de la Tourette
      syndrome (GTS). METHOD: Ten GTS patients and ten matched healthy volunteers
      underwent a simple RT paradigm (4 blocks of 50 trials). Forty acoustic startle
      reflex stimuli (110 dB) were randomly delivered with a 20% occurrence probability
      and presented unexpectedly at the same time as the imperative stimuli of the RT.
      Variables of interest were: amplitude, onset latency, degree of spread and rate
      of habituation of the startle response, and RT and the start-react effect caused
      by the startle stimuli. RESULTS: GTS patients showed a significantly higher
      amplitude, a major degree of spread and fewer habituation phenomena of the
      startle reflex. GTS patients showed poorer non statistically significant RT
      performance compared to controls, with a significant correlation between RT and
      severity of the disease. The start-react effect was significantly less pronounced
      in GTS patients. CONCLUSIONS: The present study confirms that GTS has an
      exaggerated startle reflex response and extend the spectrum of abnormalities to
      the start-react effect. A state of dopaminergic hyperactivity may have
      contributed to these results.

PMID- 10904217
TI  - The effect of baclofen on the transmission in spinal pathways in spastic multiple
      sclerosis patients.
AB  - OBJECTIVES: To measure the effect of baclofen on the transmission in different
      spinal pathways to soleus motoneurones in spastic multiple sclerosis patients.
      METHODS: Baclofen was administered orally in 14 and intrathecally in 8 patients.
      H(max)/M(max), presynaptic inhibition by biceps femoris tendon tap of femoral
      nerve stimulation, depression of the soleus H-reflex following previous
      activation of the Ia afferents from the soleus muscle (i.e. postactivation
      depression), disynaptic reciprocal Ia inhibition of the soleus H-reflex and the
      number of backpropagating action potentials in primary afferents, which may be a
      sign of presynaptic inhibition, were examined. RESULTS: Baclofen depressed the
      soleus H(max)/M(max) ratio significantly following oral and intrathecal baclofen.
      None of the two tests of presynaptic inhibition, or the postactivation depression
      or the disynaptic reciprocal Ia inhibition of the soleus H-reflex were affected
      by baclofen administration. Also the action potentials of the primary afferents
      were unchanged during baclofen administration. CONCLUSIONS: The antispastic
      effect of baclofen is not caused by an effect on the transmitter release from Ia
      afferents or on disynaptic reciprocal Ia inhibition. One possible explanation of
      the depression of the H-reflex by baclofen is suggested to be a direct depression
      of motoneuronal excitability.

PMID- 10904218
TI  - Effectiveness of motor unit potentials classification using various parameters
      and indexes.
AB  - OBJECTIVES: The aim of this study was to compare the effectiveness of quantities
      such as amplitude, duration, area, size index, number of peaks and irregularity
      coefficient applied to the classification of motor unit action potentials (MUAPs)
      in neuromuscular disorders. METHODS: We have analyzed 215 potentials recorded
      from 20 neurogenic patients and 240 potentials recorded from 14 myogenic
      patients. The statistical values for each parameter and correlation coefficients
      between parameters have been analyzed. RESULTS: The percentages of potentials
      unclassified by amplitude, duration, area/amplitude, area and size index were 31,
      34, 28, 15 and 15%, respectively. Neither the number of phases and turns nor the
      irregularity coefficient may be used for the differentiation between neuro- and
      myogenic groups. There was also a set of MUAPs that were not properly classified
      by any of the above parameters. Among the unclassified potentials there were more
      potentials from myogenic cases. These unclassified myogenic MUAPs were
      predominantly irregular, whereas most of the unclassified neurogenic MUAPs were
      simple. In neurogenic cases, parameters describing the size of the potential
      (amplitude, duration, area) were not significantly correlated with those
      describing the shape (number of phases and turns), whereas in myogenic cases some
      correlation between these parameters was significant. CONCLUSIONS: MUAP
      quantities, due to the different correlation between them in myogenic and
      neurogenic disorders, have different sensitivities. Indexes were more sensitive
      than simple parameters and were also much more effective in the evaluation of
      atypical potentials.

PMID- 10904219
TI  - Sensitivity and specificity of different conduction block criteria.
AB  - OBJECTIVES: To resolve the discrepancy between conduction block criteria derived
      from healthy controls and stricter criteria suggested by computer simulation of
      interphase cancellation through altered motor units. METHODS: An EMG database
      provided control nerves from patients with amyotrophic lateral sclerosis (ALS) or
      neural muscular atrophy (CMT1) (disease controls) and from subjects without
      neuromuscular diseases (healthy controls). We estimated normal limits from the
      healthy controls (criterion A) and from the pooled sample of healthy and disease
      controls (criterion B). We compared their sensitivity with that of an arbitrary
      limit of 0.5 (criterion C) in acute (AIDP) and chronic inflammatory demyelinating
      neuropathy (CIDP) and in multifocal motor neuropathy (MMNP). Specificity was
      assessed in ALS and CMT1. RESULTS: Limits estimated from healthy controls
      (criterion A: amplitude ratio of <0.7 in median and peroneal nerves and <0.8 in
      the ulnar nerve) gave false positive results in 17.3% of the ALS nerves. High
      scatter of the amplitude ratio of the nerves with distal response amplitudes
      below 1 mV required amplitude-dependent limits (0.36 for distal responses below 1
      mV, 0.56 between 1 and 2 mV, and between 0.67 and 0.73 for higher response
      amplitudes) for criterion B. It was false positive in 4.3% of the ALS nerves and
      in 28.3% of the CMT1 nerves. A limit of 0.5 for nerves with distal responses
      above 1 mV and a limit of 0.36 for smaller responses (criterion D) avoided false
      positive results in ALS without further impairing sensitivity per patient in
      MMNP. Sensitivity in AIDP was 34.9% for criterion A, 19.5% for criterion B, and
      10.2% for criterion D. Amplitude ratios were more sensitive than area ratios in
      CIDP and MMNP, but less specific in CMT1. CONCLUSIONS: Limits derived from
      healthy controls are unspecific in chronic neuromuscular diseases and in nerves
      with low response amplitudes. Criterion D should be used if motor unit
      restructuring or conduction delays have to be taken into account. Criterion A may
      be applicable in early AIDP if the distal response amplitude is above 1 mV.

PMID- 10904220
TI  - Sympathetic skin response in carpal tunnel syndrome.
AB  - OBJECTIVES: Sudomotor efferent nerve fiber function was studied in carpal tunnel
      syndrome (CTS). METHODS: Bilateral median and ulnar sympathetic skin response
      (SSR) were recorded by sternal stimulation in 22 bilateral and 9 unilateral
      patients and compared with 21 healthy volunteers. RESULTS: There was no
      significant difference between median and ulnar nerve SSR latency, amplitude or
      area. The median nerve SSR was not different from that of the controls. The
      median-to-ulnar ratios of SSR parameters were not different in patients and
      controls. However, the median-to-ulnar ratios of SSR amplitude and area were
      lower than normal in 3 out of 7 patients with normal nerve conduction whereas
      this abnormality was found in only 4 out of 46 patients with abnormal nerve
      conduction. CONCLUSIONS: Normal SSR results, even in patients with complaints
      related to sudomotor sympathetic dysfunction, indicate that the SSR does not seem
      to be a sensitive diagnostic method in CTS.

PMID- 10904221
TI  - Configuration of normal and abnormal non-volitional single muscle fiber
      discharges.
AB  - OBJECTIVE: This investigation utilizes a single muscle fiber simulation to
      compare and contrast single muscle fiber waveform configurations arising from
      innervated and denervated tissue taking into account possible tissue-electrode
      interactions. METHODS: Intracellular action potentials (IAPs) from innervated and
      denervated muscle tissue are simulated. The extracellular waveform configurations
      as recorded from the fiber's midpoint (endplate in innervated tissue), halfway
      between the midpoint and fiber termination, as well as fiber termination for both
      innervated and denervated single muscle fibers are examined. Further, two types
      of muscle fiber terminations are assessed: (1) sealed end effect; and (2)
      compressed end effect. RESULTS: Irrespective of different types of IAPs,
      recordings from the fibers' middle, halfway between the midpoint and termination,
      as well as from the sealed end, revealed similar configurations. However, for the
      innervated fiber's compressed termination, a monophasic positive waveform was
      derived while the denervated fiber's compressed termination generated a
      prototypical positive sharp wave. CONCLUSIONS: It is hypothesized that the needle
      electrode can no longer be considered a passive recording device but may interact
      with the fiber so as to generate a sealed end or compressed end effect. Depending
      upon the type of needle-fiber interaction and the electrode's location with
      respect to the IAP's generation site, a limited number of potentials with
      specific configurations will be recorded for both innervated and denervated
      tissue. Further, depending upon the type of needle-tissue interaction, innervated
      muscle fibers can generate non-volitional waveforms with configurations similar
      to those recorded from denervated tissue. It is no longer sufficient to merely
      consider waveform configuration when attempting to define positive sharp waves
      and fibrillation potentials, but it is important now also to consider firing rate
      and rhythm.

PMID- 10904222
TI  - Repetitive nerve stimulation: effects of recording site and the nature of
      'pseudofacilitation'.
AB  - OBJECTIVES: To describe changes in the waveform of the compound muscle action
      potential (CMAP) during repetitive nerve stimulation for various recording sites.
      METHODS: Responses to trains of 10 stimuli given at 0.1, 1, 3, 5, 10 and 30 Hz to
      the ulnar nerve were recorded simultaneously from 8 hand sites in 15 healthy
      subjects. Percentile changes of amplitude, duration and area of both negative and
      positive phases were analyzed. RESULTS: Duration consistently decreased during
      the trains. At 30 Hz, the mean amplitude of the negative phase increased on 5
      sites but decreased on 3. Area consistently decreased, but least for hypothenar
      sites. Repeated stimulation causes an alteration in the waveform of the CMAP that
      consists of 4 elements: (1) shorter duration; (2) changed amplitude of the
      negative phase (up or down); (3) merging of bifid peaks; (4) changes were more
      pronounced for positive than negative phases. CONCLUSIONS: As the term
      'pseudofacilitation' implies an increase in amplitude, it is often not
      appropriate. Increased muscle fiber conduction velocity can explain most of the
      waveform alterations. Movement and shortening of muscles may play additional
      roles. Consequences for diagnostic yield await a comparison with disease groups.

PMID- 10904223
TI  - Pitfalls of intramuscular electromyographic recordings from the human costal
      diaphragm.
AB  - OBJECTIVE: Techniques for intramuscular recordings from the costal diaphragm have
      been described. This report describes procedures to assist with precise placement
      of these electrodes using ultrasound imaging and describes several sources of
      error that must be excluded when interpreting recordings made with intramuscular
      electrodes. METHODS: Fine-wire electrodes were inserted into the left costal
      diaphragm under the guidance of ultrasound imaging in 17 healthy volunteers.
      Various respiratory maneuvers were performed to confirm the accuracy of the
      electromyographic (EMG) recordings and the electrode placement was confirmed with
      intercostal nerve blocks in one subject. RESULTS: EMG recordings can be made from
      the costal diaphragm. However, despite precise electrode placement and use of
      intramuscular electrodes with small receptive areas, the EMG recording could be
      contaminated by cross-talk (discrete motor unit activity) from the adjacent
      internal intercostal muscle and from movement of the electrode relative to the
      muscle fibers during breathing. Furthermore, it is necessary to distinguish
      between expiratory intercostal muscle activity and units in the diaphragm that
      discharge tonically throughout expiration. CONCLUSIONS: While ultrasound guidance
      of intramuscular electrode insertion can assist with accurate electrode placement
      in the diaphragm, confirmation of the stability of the recording and absence of
      cross-talk is critical to avoid misinterpretation of diaphragm function.

PMID- 10904224
TI  - Improving the clinical utility of event-related potentials.

PMID- 10904225
TI  - The auditory event-related potential is a stable and reliable measure in elderly
      subjects over a 3 year period.
AB  - OBJECTIVES: Valid markers of psychobiological processes, including changes over
      the lifespan, must be reliable. This study investigated the reliability of the
      auditory event-related potential (ERP) over a 3 year period. METHODS: Predictable
      and unpredictable rare tones were embedded in common-to-rare sequences at 3
      different ratios (2:3, 2:5 and 2:8). Forty-six older (mean age 72.3 years)
      volunteers pressed a key to the rare tones, and ERPs (Fz, Cz and Pz) and reaction
      time (RT) were measured. Reliability across years was assessed using 3 methods:
      (1) determination of the stability of waveform components (P1, N1, P2, N2 and
      P3); (2) cross-correlation of successive 15 ms epochs of within-subject ERPs; and
      (3) cross-correlation of 15 ms epochs of between-subject ERPs. RESULTS: With all
      analyses, the ERP was stable. Analysis of the scored components indicated that P3
      was especially stable in the unpredictable rare (2:8) condition. Earlier
      components were equally stable across all conditions. Analysis of 15 ms ERP
      epochs indicated significant ERP stability 60 ms after stimulation, lasting over
      640 ms. CONCLUSIONS: Robust within-subject reliability of the ERP strengthens its
      potential use for detecting preclinical changes in at-risk elderly populations.

PMID- 10904226
TI  - Effects of stimulus sequence on event-related potentials and reaction time during
      target detection in Alzheimer's disease.
AB  - OBJECTIVES: To examine evoked potentials and behavior as a function of stimulus
      sequence in an auditory target detection paradigm in Alzheimer's disease (AD).
      METHODS: Evoked potentials and reaction times were collected from 12 healthy
      elderly controls and 10 patients with mild AD. Subjects pressed a response button
      to high-pitched target tones (P=0.20) that were randomly intermixed with low
      pitched frequent tones. We measured pre-stimulus readiness potential (RP), event
      related potentials (P50, N100, P200, N200 and P300), and reaction time as a
      function of the stimulus sequence. RESULTS: AD subjects performed at comparable
      levels of accuracy as controls, but had significantly increased reaction times.
      Grand averaged potentials in AD showed a significant reduction of the amplitude
      of the RP, and an increase of P300 latency. Both controls and AD showed speeding
      of reaction time, increases in RP amplitude, and decreases in P300 latency as a
      function of the number of frequents preceding the target. Sequential changes of
      other components (P200 and N200) were found in controls but not AD. CONCLUSIONS:
      AD patients have systematic changes of both RT and certain of the evoked
      potential components as a function of stimulus sequence. Moment-by-moment changes
      in target expectancy are largely preserved in AD, even though overall performance
      and evoked potential measures of expectancy (RP) and stimulus classification
      (P300 latency) are abnormal.

PMID- 10904227
TI  - Auditory distraction: event-related potential and behavioral indices.
AB  - OBJECTIVE: The aim of this study was to illuminate behavioral and event-related
      potential (ERP) effects of attentional orienting and reorienting obtained in a
      newly developed auditory distraction paradigm, to provide more precise indicators
      about the neural generators of the ERP effects using scalp current density (SCD)
      analysis, and to evaluate the stability of the distraction effects. METHODS: In
      two sessions separated by 25 days, 10 subjects were presented with tones being of
      short (200 ms) and long (400 ms) duration equiprobably; tones were of high
      probability standard or of low-probability deviant frequency. In Distraction
      condition, subjects had to behaviorally discriminate short from long tones. In
      Ignore condition, subjects were reading a book. Behavioral performance and multi
      channel EEG were recorded. RESULTS: Task-irrelevant frequency deviations
      prolonged reaction times in the duration discrimination task by more than 35 ms
      and elicited the MMN and P3a components of the event-related potential. The P3a
      was followed by a negative deflection called RON (reorienting negativity). P3a
      and RON were absent in Ignore condition. All effects were found to be highly
      stable between sessions (product-moment correlations between 0.76 and 0.90). SCD
      analysis suggested frontal generators for P3a and for RON. CONCLUSIONS: It is
      demonstrated that small frequency deviations may yield distinct distraction
      effects in a tone duration discrimination task on a behavioral and on an
      electrophysiological level. Results support the hypothesis that frontal areas are
      involved in the exogenous orienting of attention (P3a) and in the reorienting of
      attention (RON). Due to the high stability of the deviance-related behavioral and
      ERP effects, this distraction paradigm may be utilized for clinical research.

PMID- 10904228
TI  - Gamma activity in schizophrenia: evidence of impaired network binding?
AB  - OBJECTIVES: Gamma ('40 Hz') rhythms may play a role in the integration of sensory
      processing activity. Impaired temporal integration may be a key feature of the
      associated disturbances in schizophrenia. This is the first study to examine the
      time course of Gamma activity induced in response to stimuli in this disorder.
      METHODS: Gamma activity induced in response to task-relevant and irrelevant
      auditory oddball stimuli was examined in 35 medicated schizophrenics and 35 age-
      and gender-matched normal controls. We employed a moving Welch window with short
      time FFT to examine the time course of Gamma amplitude. The amplitude spectrum
      for each time point was de-trended to eliminate any contribution of broad
      spectrum activity (EEG or EMG) to Gamma amplitude. RESULTS: For targets,
      schizophrenics showed a significant decrease in post-stimulus Gamma response
      amplitude in left hemisphere and frontal sites and an increase in right
      hemisphere and parieto-occipital sites (P<0.0009). The abnormalities correlated
      with PANSS general symptom scores. In the non-targets (at a different latency),
      schizophrenics showed a widespread Gamma decrease (P<0.0005). CONCLUSIONS: The
      Gamma findings in non-targets may reflect an abnormality in appropriately
      processing irrelevant stimuli. This could result in defective processing of the
      context (integration) of relevant target information.

PMID- 10904230
TI  - Efficient neuromagnetic determination of landmarks in the somatosensory cortex.
AB  - OBJECTIVES: An efficient procedure for the magnetoencephalographic determination
      of functional landmarks in the somatosensory cortex has been developed. METHODS:
      Digits 2-5 are stimulated in randomized order using balloon diaphragms. The
      interval between two stimuli is 500 ms. Source locations in area 3b are derived
      by interpreting the field component with a mean latency of 48 ms in terms of an
      equivalent current dipole. RESULTS: The signal-to-noise ratio achieved in a given
      time for each of the 4 stimulation sites turned out to be only slightly smaller
      than the one obtained by stimulating a single site with an optimal interstimulus
      interval (about 1 s). CONCLUSIONS: Compared to a sequential investigation of the
      different sites, the proposed procedure allows the reduction of the overall
      measurement time by a factor of about 2.7.

PMID- 10904229
TI  - Scalp distribution of the earliest cortical somatosensory evoked potential to
      tibial nerve stimulation: proposal of a new recording montage.
AB  - OBJECTIVE: To investigate the most reliable method to record the earliest
      cortical somatosensory evoked potential (SEP) after tibial nerve stimulation. The
      'gating' phenomenon was used to dissociate the overlapping cortical SEP
      components. METHODS: In 11 subjects we recorded the scalp SEPs at rest, during
      the voluntary (active gating) and passive (passive gating) foot movement and
      during the isometric calf muscle contraction (isometric gating). RESULTS: At the
      vertex the P40 amplitude was reduced in all the gating conditions. Instead, both
      the P40 response recorded in the parietal region ipsilateral to the stimulation
      (indicated as P40par) and the fronto-temporal N37 potential were reduced in
      amplitude only during the passive foot movement. CONCLUSIONS: The same behaviour
      of the N37 and P40par potentials suggests that they can represent the opposite
      counterparts of the same dipolar generator. Instead, the real P40 amplitude,
      which is affected in all the gating conditions, is recorded at the vertex and
      might be generated by a different source. We conclude that the montage obtained
      by referring a temporal electrode contralateral to the stimulation to an
      ipsilateral parietal lead can reliably record the earliest cortical component
      (N37/P40par) after tibial nerve stimulation.

PMID- 10904231
TI  - Sleep in right hemispherectomized patients: evidence of electrophysiological
      compensation.
AB  - OBJECTIVES: The goal of this study is to provide a better understanding of the
      role of the cortex in sleep's macro- and microstructure modulation. METHODS:
      Sleep architecture and phasic events were investigated in 4 patients having
      undergone right functional or anatomical hemispherectomy and 8 control subjects.
      Between-groups differences were assessed using the Wilcoxon-Mann-Whitney test.
      RESULTS: Findings provide evidence for overall similarity between patients' and
      control subjects' left hemispheric sleep architecture. In addition, results
      clearly indicate that it is possible to detect electrical activity over the
      operated side of a hemispherectomized patient's brain, even when resection of the
      hemi-cortex has been complete. Finally, findings provide evidence for similar
      left and right hemispheric relative spectral activities and for an increase in
      fast activity bands over the intact hemisphere in anatomical hemispherectomized
      patients. CONCLUSIONS: This study provides evidence that right hemispherectomy
      does not produce significant sleep architecture alterations as recorded over the
      intact hemisphere. In addition, residual activity detected over the operated side
      in anatomical hemispherectomized patients is interpreted as resulting from volume
      conduction originating from generators located in the intact hemisphere. Finally,
      there is strong evidence for electrophysiological compensation in the intact
      hemisphere following complete resection of the contralateral hemi-cortex.

PMID- 10904232
TI  - Effect of sleep stages on synchronized spontaneous otoacoustic emissions in pre
      term neonates.
AB  - OBJECTIVES: In infants, auditory tests are mainly performed during sleep, since
      they spend most of their time asleep, and because quiet is required for the
      duration of the recording session to obtain a precise and reliable response. The
      aim of this study was to investigate the effect of sleep stages on synchronized
      spontaneous otoacoustic emissions (sSOAEs) in pre-term neonates at the age where
      the sleep states begin to be well established and auditory screening can be
      performed in a neonatology unit before discharge. METHODS: Synchronized SOAEs
      were repeatedly recorded during a polygraphic sleep recording using the
      Otodynamic ILO88 system in 10 pre-term neonates at 36 weeks post-conception.
      RESULTS: Variations of sSOAE peak numbers occurred in each subject during the
      recording session. There was no clear relation between sSOAE peak number
      fluctuations and the different sleep stages. CONCLUSIONS: The sSOAE variations
      appeared to be closely related to experimental conditions, i.e. the mean
      background noise level. sSOAEs with the highest amplitude were always recorded;
      however, those with the smallest amplitude were the first to disappear from the
      recordings with higher background noise.

PMID- 10904233
TI  - Increase in alpha rhythm frequency after carotid endarterectomy.
AB  - OBJECTIVES: Besides preventing stroke, carotid endarterectomy (CEA) is reported
      to improve cerebral circulation and brain function. We tested whether this
      improvement is reflected by changes in the qEEG. METHODS: qEEG changes in 166
      patients with a >70% stenosis of the internal carotid artery (ICA) were assessed
      after subtraction of the preoperative and postoperative spectra (eyes closed
      condition) before and 3 months after CEA. The mean frequency of the alpha band
      (MFA), the peak frequency of the alpha band (F alpha), and bands with limits
      relative to each patient's F alpha were studied in relation to neurological
      symptoms, patency or occlusion of the contralateral ICA, shunt requirement, and
      side of surgery. RESULTS: MFA and F alpha significantly increased over both
      hemispheres. After alignment on F alpha, a decrease of spectral band power was
      seen below F alpha, and a band power increase above F alpha. The group of
      patients with a contralateral ICA occlusion showed significantly more improvement
      than the group without. The group of patients with neurological deficits showed a
      tendency for improvement. No differences were found concerning shunt requirement
      or the side of surgery. CONCLUSIONS: After CEA the alpha rhythm frequency
      increases. In general, patients with a contralateral ICA occlusion improve more
      than other patients, in agreement with data from the literature on cerebral
      circulation and brain function.

PMID- 10904234
TI  - Estimation of the electric conductivity from scalp measurements: feasibility and
      application to source localization.
AB  - OBJECTIVES: The accuracy of electrical impedance tomography was investigated.
      METHODS: The conductivities of the different compartments of the volume conductor
      were estimated by utilizing the boundary element method. The approach was tested
      for realistic head models with either 3 or 4 compartments. The impact of a
      geometrical error in the head model was investigated and the estimated
      conductivities were assigned to the compartments of the volume conductor used for
      the source imaging. The localization errors were quantified. RESULTS: The method
      used allowed the estimation of the conductivity of the compartments. The poor
      conductivity of the skull decreased the precision with which the conductivity of
      deeper structures could be estimated. A geometrical error in the head model was
      compensated by the estimated conductivities. However, the estimated
      conductivities did not cancel the geometrical error in the head model as
      localization errors of the order of 10-20 mm were obtained. CONCLUSIONS: In
      principle, the conductivity estimation of the distinct regions in the head is
      possible. The application of conductivity estimation to increase the accuracy of
      source localization remains questionable.

PMID- 10904235
TI  - The chronotherapeutics of hypertension

PMID- 10904236
TI  - Factors affecting circadian variability.
AB  - Several unfavorable cardiovascular events show a well-defined pattern in their
      occurrence throughout the day. Myocardial infarction and ischemia, sudden cardiac
      death and stroke occur with greater frequency in the morning hours after
      awakening. Multiple biologic functions such as blood pressure, heart rate,
      sympathetic neurotransmission, vascular tone, platelet aggregability, and
      coagulation parameters also show a diurnal variation and appear to contribute to
      adverse cardiac outcomes. Recent studies have emphasized the importance of 24 h
      control in decreasing cardiovascular risk. The renin-angiotensin system (RAS),
      through the important effector peptide, angiotensin II (Ang II), has potent
      effects on blood pressure, salt and water homeostasis, and target-organ damage.
      Inhibiting the RAS consequently becomes an important therapeutic avenue for
      treating hypertension and target-organ damage. Ang II receptor antagonists
      selectively compete with the binding of Ang II to the Ang II type 1 receptor and,
      by inhibiting the multiple activities mediated by Ang II at this receptor, may
      confer cardiovascular benefits additional to that of blood pressure control. Ang
      II receptor antagonists with an intrinsically long duration of action that
      produce smooth, sustained antihypertensive activity over the dosing period
      provide a similar 24 h benefit of Ang II inhibition.

PMID- 10904237
TI  - The importance of blood pressure variability in hypertension.
AB  - Use of ambulatory blood pressure monitoring (ABPM) techniques has revealed that
      blood pressure is characterized by a considerable degree of variability over a 24
      h period as a result, not only of the well-known fluctuations that occur between
      wakefulness and sleep, but also of the minute-to-minute changes induced by a
      variety of behavioural conditions. The degree of these variations is also
      influenced by neural mechanisms responsible for cardiovascular regulation, such
      as the arterial baroreflex. Blood pressure variability increases with age and
      blood pressure values, and its magnitude has been shown to correlate
      independently with the target-organ damage of hypertension. This has stimulated
      both the development of antihypertensive drugs able to reduce blood pressure
      homogeneously over 24 h, and recent proposals to develop more accurate indices,
      such as the smoothness index, to quantify the distribution of the
      antihypertensive effect over the entire day and night. Despite the important
      information that ABPM can provide concerning daily-life blood pressure variations
      and their modification by treatment, international guidelines suggest that it
      should not yet be used routinely in daily practice, but rather reserved for
      selected patients.

PMID- 10904238
TI  - Ambulatory blood pressure monitoring: dippers compared with non-dippers.
AB  - Epidemiologic studies have demonstrated that the peak incidence of most types of
      cardiovascular disease follows a circadian (24 h) pattern. Ambulatory monitoring
      studies have documented a reproducible 24 h rhythm for blood pressure,
      characterized by a period of low values during sleep, an early-morning increase
      in pressures, and a plateau period while the individual is awake and active.
      Hypertensive patients who display the typical nocturnal decrease in blood
      pressure are termed 'dippers', whereas patients in whom the nocturnal decrease in
      blood pressure is absent or blunted are termed 'non-dippers'. The circadian
      rhythm may be influenced by demographic, neurohormonal, and pathophysiologic
      factors. The non-dipper profile appears to be of prognostic significance because
      it is associated with increased target-organ damage and a worsened cardiovascular
      outcome. Chronotherapy is a new pharmacologic concept whereby medication is
      delivered at a time and in a concentration that varies according to physiologic
      need during the dosing period. Of greatest interest is the reduction in blood
      pressure during the early-morning blood pressure surge, as that time is
      associated with an increased risk for myocardial infarction and stroke. Factors
      that may increase the early-morning blood pressure include activation of the
      sympathetic nervous system and the renin-angiotensin-aldosterone system. In the
      near future, the benefits of a chronotherapeutic approach to the management of
      hypertension should be elucidated by large-scale outcome studies.

PMID- 10904239
TI  - Intrinsically long-acting agents compared with long-acting chronoformulations.
AB  - Intrinsically long-acting antihypertensive drugs may be characterized by long
      elimination half-lives with high trough: peak ratios for decreasing blood
      pressure. These agents are usually administered once daily in the morning, and at
      steady-state they provide 24 h blood pressure control, attenuate the early
      morning surge in blood pressure, and maintain a normal circadian blood pressure
      pattern. In comparison, chronoformulations incorporate shorter-acting
      antihypertensive drugs into a delivery system that is delayed-onset or extended
      release, or both. These agents, which are often designed to be given once daily
      at bedtime, deliver peak drug concentrations that coincide with the early-morning
      surge in blood pressure. Chronoformulations also provide 24 h blood pressure
      control. In highly compliant patients, both intrinsically long-acting drugs and
      chronoformulations are likely to provide comparable blood pressure control.
      However, in poorly compliant patients who miss doses of medication, intrinsically
      long-acting drugs are likely to be superior, because they sustain blood pressure
      control beyond the dosing interval.

PMID- 10904240
TI  - Long-term compliance with antihypertensive therapy: another facet of
      chronotherapeutics in hypertension.
AB  - Despite improvements in the management of hypertension in the past several years
      and the numerous efficacious antihypertensive agents available to today's
      physician, nearly 70% of patients do not have their hypertension adequately
      controlled. Noncompliance with prescribed regimens appears to be one of the
      primary contributors to the large numbers of patients with uncontrolled
      hypertension. A behaviour that can affect all patients, noncompliance is
      perplexing because it remains largely unrecognized in clinical practice. Several
      types of noncompliance exist, the 'drug holiday' being the most common. Good
      communication with the patient and the entire health care team is essential to
      improving patient compliance. Long-acting medications that provide good control
      of blood pressure beyond the 24 h dosing period should be considered as the drugs
      of choice in noncompliant hypertensive patients. This article discusses different
      types of compliance, methods of measuring compliance, and the clinical
      consequences of noncompliance in hypertension.

PMID- 10904241
TI  - Use of ambulatory blood pressure monitoring to evaluate the selective angiotensin
      II receptor antagonist, telmisartan, and other antihypertensive drugs.
AB  - Telmisartan (Micardis (R)) is a new, orally active, long-acting angio-tensin
      (Ang) II receptor antagonist that is effective in the treatment of hypertension.
      Ambulatory blood pressure monitoring (ABPM) has emerged as an important method
      for evaluating the consistency of the antihypertensive effects of a drug
      throughout the dosing interval. ABPM was used to evaluate the antihypertensive
      efficacy of telmisartan in several placebo-controlled, double-blind, multicenter
      studies. Patients with mild-to-moderate hypertension were allocated randomly to
      groups to receive telmisartan 40 or 80 mg, losartan 50 mg, or placebo, once daily
      in a 6-week, fixed-dose study, or telmisartan 40-120 mg, amlodipine 5-10 mg, or
      placebo, once daily in a 12-week, dose-titration study. Patients treated with
      telmisartan 40 and 80 mg or placebo in a separate 4-week, fixed-dose study were
      included in an additional analysis. Telmisartan 40 and 80 mg significantly
      decreased mean ambulatory systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) relative to placebo for the entire 24 h period and in the
      following intervals: day (6 a.m. to 10 p.m.), morning (6 a.m. to noon), night (10
      p.m. to 6 a.m), and the last 4 h of the dosing interval (P<0.01). Notably,
      telmisartan 40 or 80 mg was more effective than losartan, especially during the
      last 4-6 h of the dosing interval (P<0.05). Telmisartan 40- 120 mg tended to be
      more effective than amlodipine 5-10 mg in reducing SBP and DBP in each time
      interval, with significant differences between treatments noted for DBP in the
      last 4 h of the dosing interval and in the morning (P < 0.05). ABPM also revealed
      that the magnitude of the blood pressure decreasing effect with telmisartan was
      consistent throughout the dosing interval. These results demonstrate that
      telmisartan maintains a normal circadian blood pressure pattern and provides full
      24 h blood pressure control with once-daily dosing.

PMID- 10904242
TI  - A role for Borna disease virus in schizophrenia?

PMID- 10904243
TI  - Cellular defect at the heart of cardiac failure.

PMID- 10904244
TI  - Hypnosis moves one step closer to the medical mainstream.

PMID- 10904245
TI  - New data confirm that HPV can cause oropharyngeal cancer.

PMID- 10904246
TI  - Migraine: more than just a headache.

PMID- 10904247
TI  - The molecular role of mast cells in atherosclerotic cardiovascular disease.
AB  - Human atherosclerosis has many characteristics of an inflammatory disorder.
      Recent data suggest that mast cells might be important in the pathogenesis of
      atherosclerotic disease. By secretion of pro-inflammatory cytokines, mast cells
      can assist in the recruitment of monocytes and lymphocytes into vascular tissue,
      thereby propagating the inflammatory response. Mast cell enzymes might activate
      pro-metalloproteinases, thereby destabilizing atheromatous plaques. Mast cells
      can facilitate foam cell formation by promoting cholesterol accumulation.
      However, mast cell tryptase could slow thrombus formation at sites of plaque
      rupture by interfering with coagulation. Therefore, mast cells can modulate
      coronary artery disease by both facilitatory and inhibitory pathways.

PMID- 10904248
TI  - Molecular strategies for overcoming antibiotic resistance in bacteria.
AB  - Overuse of antibiotics in humans and livestock has led to the rapid evolution of
      bacteria that are resistant to multiple drugs such that even vancomycin, the drug
      of last resort, is no longer effective against some strains. Apart from the
      discovery and exploitation of the natural peptide antimicrobial agents that form
      part of the innate immune systems of plants and animals, there have been few new
      antibiotics developed in recent years. Here we review strategies designed to
      exploit recent advances in molecular biology, including recombinant DNA
      technology, molecular modelling and genomics to develop new antibacterial agents
      that overcome antibiotic resistance.

PMID- 10904249
TI  - Cytokines in rheumatoid arthritis: trials and tribulations.
AB  - Biological agents that inhibit the activity of proinflammatory cytokines are
      being investigated for use in the treatment of rheumatoid arthritis. Thus far,
      two of these agents, both of which neutralize tumor necrosis factor alpha (TNF
      alpha), have received US Food and Drug Administration approval for the treatment
      of the disease. Etanercept is a bioengineered fusion protein of the p75 soluble
      TNF receptor, and infliximab is a chimeric monoclonal antibody to TNF-alpha.
      Other agents that target proinflammatory cytokines are also being developed. By
      allowing earlier treatment and better-tolerated long-term therapy, biologics
      might help slow or prevent disease progression and joint destruction.

PMID- 10904250
TI  - The influence of the microenvironment on the malignant phenotype.
AB  - Normal tissue homeostasis is maintained by dynamic interactions between
      epithelial cells and their microenvironment. As tissue becomes cancerous, there
      are reciprocal interactions between neoplastic cells, adjacent normal cells such
      as stroma and endothelium, and their microenvironments. The current dominant
      paradigm wherein multiple genetic lesions provide both the impetus for, and the
      Achilles heel of, cancer might be inadequate to understand cancer as a disease
      process. In the following brief review, we will use selected examples to
      illustrate the influence of the microenvironment in the evolution of the
      malignant phenotype. We will also discuss recent studies that suggest novel
      therapeutic interventions might be derived from focusing on microenvironment and
      tumor cells interactions.

PMID- 10904252
TI  - Implicit motion and the brain.

PMID- 10904251
TI  - A mouse model of myocardial stunning.

PMID- 10904253
TI  - Implied motion activates extrastriate motion-processing areasResponse to David
      and Senior (2000).

PMID- 10904254
TI  - Perceptual causality and animacy.
AB  - Certain simple visual displays consisting of moving 2-D geometric shapes can give
      rise to percepts with high-level properties such as causality and animacy. This
      article reviews recent research on such phenomena, which began with the classic
      work of Michotte and of Heider and Simmel. The importance of such phenomena stems
      in part from the fact that these interpretations seem to be largely perceptual in
      nature - to be fairly fast, automatic, irresistible and highly stimulus driven -
      despite the fact that they involve impressions typically associated with higher
      level cognitive processing. This research suggests that just as the visual system
      works to recover the physical structure of the world by inferring properties such
      as 3-D shape, so too does it work to recover the causal and social structure of
      the world by inferring properties such as causality and animacy.

PMID- 10904256
TI  - Steering with or without the flow: is the retrieval of heading necessary?

PMID- 10904255
TI  - Imprinted genes, cognition and behaviour.
AB  - The idea that genes can influence behavioural predispositions and their
      underlying psychological determinants is becoming increasingly tractable. In this
      article, recent findings are reviewed on a special type of inheritance, related
      to the transmission of traits via what have been termed 'imprinted' genes. In
      imprinted genes one allele is silenced according to its parental origin. This
      results in the inheritance of traits down the maternal or paternal line, in
      contrast to the more frequent mode of inheritance that is indifferent to the
      parental origin of the allele. Drawing on the advances made possible by combining
      the approaches of cognitive neuropsychology, behavioural neuroscience and
      contemporary molecular genetics, the detailed evidence for imprinted effects on
      behavioural and cognitive phenotypes is considered, focusing on findings from
      mental disorders, Turner's syndrome and experimental work in animal models. As
      prevailing evolutionary theories stress an essential antagonistic role of
      imprinted effects, these data might link such apparently diverse issues as
      neurodevelopment and the vulnerability to mental disease with the 'battle of the
      sexes', as joined at the level of cognitive and behavioural functioning.

PMID- 10904257
TI  - Cancer classification with DNA microarrays is less more?
AB  - The dissection of cancer and the underlying molecular processes that are
      defective in cancer cells has become an important tool in the fight against this
      disease. DNA microarrays can provide detailed information of the expression
      pattern of thousands of genes in tumours. But how much of this data is useful and
      is some superfluous? Can array data be used to identify a handful of critical
      genes that will lead to a more-detailed taxonomy of tumours and can this or
      similar array data be used to predict clinical outcome? Primary tumours will give
      us the statistical power to draw these conclusions, but can cancer cell lines be
      used as models to point us in the right direction?

PMID- 10904258
TI  - Science funding and infrastructures in Europe.
AB  - European science in crisis. Scared? Then read on; you should be. I argue that we
      cannot sit back for much longer and watch our best scientists emigrate to the USA
      for the most productive part of their career, and that European scientists should
      not tolerate a funding system that neither rewards an investigator's brilliance
      nor the innovative nature of their research. The EC Framework Programme is due
      for a face lift: scientists should wield the scalpel this time.

PMID- 10904259
TI  - Genome size and longevity.

PMID- 10904260
TI  - No footprints of primordial introns in a eukaryotic genome.

PMID- 10904261
TI  - SNP frequencies in human genes an excess of rare alleles and differing modes of
      selection.

PMID- 10904262
TI  - Peroxisome biogenesis disorders: genetics and cell biology.
AB  - Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease and
      rhizomelic chondrodysplasia punctata are progressive disorders characterized by
      loss of multiple peroxisomal metabolic functions. These diseases are inherited in
      an autosomal recessive manner, are caused by defects in the import of peroxisomal
      matrix proteins and are referred to as the peroxisome biogenesis disorders
      (PBDs). Recent studies have identified the PEX genes that are mutated in 11 of
      the 12 known complementation groups of PBD patients. This article reviews these
      advances in PBD genetics and discusses how studies of human PEX genes, their
      protein products and PBD cell lines are shaping current models of peroxisome
      biogenesis.

PMID- 10904263
TI  - The Swi/Snf family nucleosome-remodeling complexes and transcriptional control.
AB  - The Swi/Snf family of nucleosome-remodeling complexes has been shown to play
      important roles in gene expression throughout eukaryotes. Genetic and biochemical
      studies previously suggested that Swi/Snf activates transcription by remodeling
      nucleosomes, thereby permitting increased access of transcription factors for
      their binding sites. Recent studies have identified additional Swi/Snf
      biochemical activities and have suggested possible mechanisms by which Swi/Snf is
      targeted to specific promoters. Surprisingly, studies have also revealed that,
      besides being necessary for activation, Swi/Snf is required for transcriptional
      repression of some genes. These analyses have transformed our understanding of
      the function of the Swi/Snf family of complexes and suggest that they control
      transcription in diverse ways.

PMID- 10904264
TI  - NuRD and SIN3 histone deacetylase complexes in development.
AB  - Transcription repression mediated through histone deacetylase (HDAC) complexes is
      widespread, and mechanisms by which HDAC complexes act have been revealed by
      extensive studies in vitro and in cell culture. However, until recently, little
      has been known about the developmental roles of histone deacetylation. Mutants
      now exist for a number of members of the two major HDAC complexes (NuRD and SIN3)
      and some associated proteins. The emerging picture is that these complexes have
      specific functions in development, rather than being required for most cellular
      processes.

PMID- 10904265
TI  - New uses for new haplotypes the human Y chromosome, disease and selection.
AB  - Recent discoveries of many new genes have made it clear that there is more to the
      human Y chromosome than a heap of evolutionary debris, hooked up to a sequence
      that happens to endow its bearer with testes. Coupled with the recent development
      of new polymorphic markers on the Y, making it the best-characterized haplotypic
      system in the genome, this gives us new opportunities to assess its role in
      disease and selection, through association studies with phenotypes such as
      infertility and cancers. However, the peculiar genetics of this bizarre
      chromosome means that we should interpret such studies particularly cautiously.

PMID- 10904266
TI  - RTK mutations and human syndromes: when good receptors turn bad

PMID- 10904267
TI  - Doppler echocardiographic study in adolescents and young adults with sickle cell
      anemia.
AB  - OBJECTIVE: Anatomical and functional assessment of the heart through Doppler and
      echocardiography in patients with cell anemia (SCA). METHODS: Twenty-five
      patients with SCA and ages ranging from 14 to 45 years were prospectively studied
      in a comparison with 25 healthy volunteers. All of them underwent clinical and
      laboratory evaluation and Doppler echocardiography as well. The measurements were
      converted into body surface indices. RESULTS: There were increases in all chamber
      diameters and left ventricle (LV) mass of the SCA patients. It was characterised
      an eccentric hypertrophy of the left ventricle. The preload was increased (left
      ventricle end-diastolic volume) and the afterload was decreased (diastolic blood
      pressure, peripheral vascular resistance and end-systolic parietal stress ESPS).
      The cardiac index was increased due to the stroke volume. The ejection fraction
      and the percentage of the systolic shortening, as well as the systolic time
      intervals of the LV were equivalent. The isovolumetric contraction period of the
      LV was increased. The mitral E-septum distance and the end-systolic volume index
      (ESVi) were increased. The ESPS/ESVi ratio,a loading independent parameter, was
      decreased in SCA, suggesting systolic dysfunction. No significant differences in
      the diastolic function or in the pulmonary pressure occurred. CONCLUSION: Chamber
      dilations, eccentric hypertrophy and systolic dysfunction confirm the evidence of
      the literature in characterizing a sickle cell anemia cardiomyopathy.

PMID- 10904268
TI  - Primary coronary angioplasty and stent implantation in acute myocardial
      infarction. Comparative analysis of the in-hospital results in the CENIC/SBHCI
      registry. National Center of Cardiovascular Interventions members.
AB  - OBJECTIVE: Comparative analysis of the in-hospital results after primary
      implantation of stents or coronary balloon angioplasty in patients with acute
      myocardial infarction (MI). METHODS: CENIC (National Center of Cardiovascular
      Interventions) gathered data on 3, 924 patients undergoing coronary angioplasty
      (in the primary form, without the previous use of thrombolytic agents) in the
      first 24 hours after a MI, during the period of 1996-1998. From these 3,924
      patients, 1,337 (34%) underwent stent implantation. We analyzed the success of
      the procedure and the occurrence of adverse cardiac events. RESULTS: In patients
      undergoing stent implantation there were more males (77% vs 69%, p=0.001),
      previous by pass surgery (6. 3% vs. 4.5%, p=0.01), anterior MI and stent
      implantation in left descending artery (55% vs. 48% vs. p=0.009), and saphenous
      vein bypass grafts (3.3% vs. 1.9%). the procedure was more succesful in the group
      of stents (97% vs. 84%, p=0.001) and reinfarction rate (2. 5 vs. 4%, p=0.002).
      The need for emergency revascularization was similar (1% vs. 1.1%, NS). Total in
      hospital mortality was lower in stent group (3.4% vs. 7. 2%, p=0.0001) and this
      effect was in patients Killip class III/V (19.5% vs. 32.5%, p= 0.002) because
      there was no difference in patients class I/II (1.7% vs. 2.8%, p=0. 9).
      CONCLUSION: Primary stent implantation in acute myocardial infarction showed
      better early results than balloon angioplasty alome.

PMID- 10904270
TI  - Endomyocardial fibrosis associated with massive calcification of the left
      ventricle.
AB  - This is the report of a rare case of endomyocardial fibrosis associated with
      massive calcification of the left ventricle in a male patient with dyspnea on
      great exertion, which began 5 years earlier and rapidly evolved. Due to lack of
      information and the absence of clinical signs that could characterize impairment
      of other organs, the case was initially managed as a disease with a pulmonary
      origin. With the evolution of the disease and in the presence of radiological
      images of heterogeneous opacification in the projection of the left ventricle,
      the diagnostic hypothesis of endomyocardial disease was established. This
      hypothesis was later confirmed on chest computed tomography. The patient died on
      the 16th day of the hospital stay, probably because of lack of myocardial
      reserve, with clinical findings of refractory heart failure, possibly aggravated
      by pulmonary infection. This shows that a rare disease such as endomyocardial
      fibrosis associated with massive calcification of the left ventricle may be
      suspected on a simple chest X-ray and confirmed by computed tomography.

PMID- 10904269
TI  - Right ventricular bifocal stimulation in the treatment of dilated cardiomyopathy
      with heart failure.
AB  - OBJECTIVE: To describe a new more efficient method of endocardial cardiac
      stimulation, which produces a narrower QRS without using the coronary sinus or
      cardiac veins. METHODS: We studied 5 patients with severe dilated cardiomyopathy,
      chronic atrial fibrillation and AV block, who underwent definitive endocardial
      pacemaker implantation, with 2 leads, in the RV, one in the apex and the other in
      the interventricular septum (sub pulmonary), connected, respectively, to
      ventricular and atrial bicameral pacemaker outputs. Using Doppler
      echocardiography, we compared, in the same patient, conventional (VVI), high
      septal ("AAI") and bifocal ("DDT" with AV interval approximately 0) stimulation.
      RESULTS: The RV bifocal stimulation had the best results with an increase in
      ejection fraction and cardiac output and reduction in QRS duration, mitral
      regurgitation and in the left atrium area (p </= 0.01). The conventional method
      of stimulation showed the worst result. CONCLUSION: These results suggest that,
      when left ventricular stimulation is not possible, right ventricular bifocal
      stimulation should be used in patients with severe cardiomyopathy where a
      pacemaker is indicated.

PMID- 10904271
TI  - The patient is a 46-year-old female with marked myocardial hypertrophy and heart
      failure.

PMID- 10904272
TI  - Use of sildenafil in patients with cardiovascular disease.

PMID- 10904275
TI  - Univentricular atrioventricular connection. Review of the current therapeutical
      possibilities.

PMID- 10904273
TI  - Evaluation of the treadmill stress testing for risk stratification after acute
      myocardial infarction.

PMID- 10904274
TI  - Specialized computer support systems for medical diagnosis. Relationship with the
      Bayes' theorem and with logical diagnostic thinking.

PMID- 10904276
TI  - Permanent and temporary pacemaker implantation after orthotopic heart
      transplantation.
AB  - PURPOSE:To determine the indication for and incidence and evolution of temporary
      and permanent pacemaker implantation in cardiac transplant recipients. METHODS: A
      retrospective review of 114 patients who underwent orthotopic heart
      transplantation InCor (Heart Institute USP BR) between March 1985 and May 1993.
      We studied the incidence of and indication for temporary pacing, the relationship
      between pacing and rejection, the need for pemanent pacing and the clinical
      follow-up. RESULTS: Fourteen of 114 (12%)heart transplant recipients required
      temporary pacing and 4 of 114 (3.5%) patients required permanent pacing. The
      indication for temporary pacing was sinus node dysfunction in 11 patients (78.5%)
      and atrioventricular (AV) block in 3 patients (21.4%). The indication for
      permanent pacemaker implantation was sinus node dysfunction in 3 patients (75%)
      and atrioventricular (AV) block in 1 patient (25%). We observed rejection in 3
      patients (21.4%) who required temporary pacing and in 2 patients (50%) who
      required permanent pacing. The previous use of amiodarone was observed in 10
      patients (71.4%) with temporary pacing. Seven of the 14 patients (50%) died
      during follow-up. CONCLUSION: Sinus node dysfunction was the principal indication
      for temporary and permanent pacemaker implantation in cardiac transplant
      recipients. The need for pacing was related to worse prognosis after cardiac
      transplantation.

PMID- 10904277
TI  - Chest pain in the emergency room. Importance of a systematic approach.
AB  - OBJECTIVE: To evaluate the efficiency of a systematic diagnostic approach in
      patients with chest pain in the emergency room in relation to the diagnosis of
      acute coronary syndrome (ACS) and the rate of hospitalization in high-cost units.
      METHODS: One thousand and three consecutive patients with chest pain were
      screened according to a pre-established process of diagnostic investigation based
      on the pre-test probability of ACS determinate by chest pain type and ECG
      changes. RESULTS: Of the 1003 patients, 224 were immediately discharged home
      because of no suspicion of ACS (route 5) and 119 were immediately transferred to
      the coronary care united because of ST elevation or left bundle-branch block
      (LBBB) (route 1) (74% of these had a final diagnosis of acute myocardial
      infarction [AMI]). Of the 660 patients that remained in the emergency room under
      observation, 77 (12%) had AMI without ST segment elevation and 202 (31%) had
      unstable angina (UA). In route 2 (high probability of ACS) 17% of patients had
      AMI and 43% had UA, whereas in route 3 (low probability) 2% had AMI and 7 % had
      UA. The admission ECG has been confirmed as a poor sensitivity test for the
      diagnosis of AMI ( 49%), with a positive predictive value considered only
      satisfactory (79%). CONCLUSION: A systematic diagnostic strategy, as used in this
      study, is essential in managing patients with chest pain in the emergency room in
      order to obtain high diagnostic accuracy, lower cost, and optimization of the use
      of coronary care unit beds.

PMID- 10904278
TI  - The results of the Campaign for evaluating sphygmomanometers accuracy and their
      physical conditions.
AB  - OBJECTIVE: To evaluate the sphygmomanometers calibration accuracy and the
      physical conditions of the cuff-bladder, bulb, pump, and valve. METHODS: Sixty
      hundred and forty five aneroid sphygmomanometers were evaluated, 521 used in
      private practice and 124 used in hospitals. Aneroid manometers were tested
      against a properly calibrated mercury manometer and were considered calibrated
      when the error was </=3mm Hg. The physical conditions of the cuffs-bladder, bulb,
      pump, and valve were also evaluated. RESULTS: Of the aneroid sphygmomanometers
      tested, 51% of those used in private practice and 56% of those used in hospitals
      were found to be not accurately calibrated. Of these, the magnitude of inaccuracy
      ranged from 4 to 8mm Hg in 70% and 51% of the devices, respectively. The problems
      found in the cuffs - bladders, bulbs, pumps, and valves of the private practice
      and hospital devices were bladder damage (34% vs. 21%, respectively), holes/leaks
      in the bulbs (22% vs. 4%, respectively), and rubber aging (15% vs. 12%,
      respectively). Of the devices tested, 72% revealed at least one problem
      interfering with blood pressure measurement accuracy. CONCLUSION: Most of the
      manometers evaluated, whether used in private practice or in hospitals, were
      found to be inaccurate and unreliable, and their use may jeopardize the diagnosis
      and treatment of arterial hypertension.

PMID- 10904279
TI  - Acute myocardial infarction in the Brazilian State of Sao Paulo. In-hospital
      deaths from 1979 to 1996 and hospital fatality from 1984 to 1998 in the public
      health system.
AB  - OBJECTIVE: To determine the following parameters in the Brazilian State of Sao
      Paulo: 1) the percentage of deaths due to acute myocardial infarction (AMI)
      occurring in hospitals; 2) the percentage of deaths due to AMI occurring in
      public health system hospitals as compared with all in-hospital deaths due to AMI
      between 1979 and 1996; 3) the fatality due to AMI in public health system
      hospitals from 1984 to 1998. METHODS: Data were available on the Datasus Web site
      (the health information agency of the Brazilian Department of Health) that
      provided the following: a) number of deaths resulting from AMI in hospitals; b)
      number of deaths resulting from AMI in public health system hospitals; c) number
      of hospital admissions due to AMI in public health system hospitals. RESULTS: The
      percentage of in-hospital deaths due to AMI increased from 54.9 in 1979 to 68.6
      in 1996. The percentage contribution of the public health system to total number
      of deaths due to AMI occurring in hospitals decreased from 22.9 in 1984 to 13.7
      in 1996; fatality due to AMI occurring in public health system hospitals had an
      irregular evolution from 1984 to 1992 and showed a slight trend for increased
      frequency from 1993 to 1998. CONCLUSION: The percentage of in-hospital deaths due
      to AMI has been increasing. Deaths resulting from AMI in public health system
      hospitals have decreased when compared with the total number of deaths due to AMI
      in all hospitals. Fatality due to AMI in public health system hospitals did not
      decrease from 1992 to 1998.

PMID- 10904280
TI  - Constrictive pericarditis in a 19-month-old child.
AB  - We report a case of chronic nonspecific constrictive pericarditis with myocardial
      involvement in a 19-month-old infant. The patient underwent total pericardiectomy
      and had irreversible hemodynamic instability. Constrictive pericarditis is rare
      in childhood. It may follow several processes, most frequently an infectious
      disease. The natural course of the disease consists of progressive myocardial
      dysfunction with atrioventricular valvular involvement. When diagnosis is
      established early in the course of the disease and treatment started immediately,
      the evolution is favorable in most instances.

PMID- 10904282
TI  - Transmission of infectious diseases through mouth-to-mouth ventilation: evidence
      based or emotion-based medicine?

PMID- 10904281
TI  - Lupus carditis.

PMID- 10904283
TI  - [Mario Rigatto, my master (28/12/1928-17/1/2000)].

PMID- 10904284
TI  - Reduction in left ventricular hypertrophy in hypertensive patients treated with
      enalapril, losartan or the combination of enalapril and losartan.
AB  - OBJECTIVE: To compare the regression of left ventricular hypertrophy in patients
      with moderate hypertension treated with enalapril, losartan or a combination of
      the two drugs at lower doses. METHODS: Patients of both sexes with moderate
      hypertension confirmed by ambulatory monitoring of arterial blood pressure and
      with left ventricular hypertrophy on echocardiogram were assigned to three
      groups: enalapril (35 mg/day, n=15), losartan (175 mg/day, n=15) and enalapril
      losartan (15 mg+100 mg/day, n=16). The patients received the drugs for 10 months.
      RESULTS: The three therapeutic regimens were equally effective in reducing blood
      pressure and left ventricular mass index (LVMI, g/m2): 141+/-3.9 to 123+/-3.6 in
      the enalapril group (p<0.05), from 147+/-3.8 to 133+/-2.8 in the losartan group
      (p<0.05), and from 146+/-3.0 to 116+/-4.0 in the enalapril+losartan group
      (p<0.05). However, the percent reduction of LVMI was significantly greater
      (p<0.01) in the enalapril+losartan group (20.5+/-5.0%) than in enalapril (12.4+/
      3.2%) and the losartan (9.1+/-2.1%) groups. Normalization of LVMI was obtained in
      10 out of the 16 patients who received enalapril+ losartan, in 6 out of the 15
      patients who received only enalapril and in 4 out of the 15 patients treated with
      losartan. CONCLUSION: The combination of an angiotensin-converting enzyme
      inhibitor and an angiotensin II receptor antagonist (AT1 receptor antagonist) in
      patients produced an additional effect on the reduction of left ventricular
      hypertrophy. This finding may depend on a more complete inhibition of the cardiac
      renin-angiotensin.

PMID- 10904285
TI  - Chlamydia pneumoniae and atherosclerosis. Identification of bacterial DNA in the
      arterial wall.
AB  - OBJECTIVE: The intracellular Gram-negative bacterium Chlamydia pneumoniae has
      been associated with atherosclerosis. The presence of Chlamydia pneumoniae has
      been investigated in fragments of the arterial wall with a technique for DNA
      identification. METHODS: Arterial fragments obtained from vascular surgical
      procedures in 58 patients were analyzed. From these patients, 39 were males and
      the mean age was 65+/-6 years. The polymerase chain reaction was used to identify
      the bacterial DNA with a pair of primers that codify the major outer membrane
      protein (MOMP) of Chlamydia pneumoniae. The amplified product was visualized by
      electrophoresis in the 2% agarose gel stained with ethidium bromide, and it was
      considered positive when migrating in the band of molecular weight of the
      positive controls. RESULTS: Seven (12%) out of the 58 patients showed positive
      results for Chlamydia pneumoniae. CONCLUSION: DNA from Chlamydia pneumoniae was
      identified in the arterial wall of a substantial number of patients with
      atherosclerosis. This association, which has already been described in other
      countries, corroborates the evidence favoring a role played by Chlamydia
      pneumoniae in atherogenesis.

PMID- 10904286
TI  - A new surgical approach for treating dilated cardiomyopathy with mitral
      regurgitation.
AB  - OBJECTIVE: To evaluate the early outcome of mitral valve prostheses implantation
      and left ventricular remodeling in 23 patients with end-stage cardiomyopathy and
      secondary mitral regurgitation (NYHA class III and IV). METHODS: Mitral valvular
      prosthesis implantation with preservation of papillary muscles and chordae
      tendinae, and plasty of anteriun cuspid for remodeling of the left ventricle.
      RESULTS: The surgery was performed in 23 patients, preoperative ejection fraction
      (echocardiography) varied from 13% to 44% (median: 30%). In 13 patients
      associated procedures were performed: myocardial revascularization (9), left
      ventricle plicature repair (3) and aortic prosthesis implantation (1). Early
      deaths (2) occurred on the 4th PO day (cardiogenic shock) and on the 20th PO day
      (upper gastrointestinal bleeding), and a late death in the second month PO
      (ventricular arrhythmia). Improvement occurred in NYHA class in 82. 6% of the
      patients (P<0.0001), with a survival rate of 86.9% (mean of 8.9 months of follow
      up). CONCLUSION: This technique offers a promising therapeutic alternative for
      the treatment of patients in refractory heart failure with cardiomyopathy and
      secondary mitral regurgitation.

PMID- 10904287
TI  - Treatment of persistent rejection with methotrexate in stable patients submitted
      to heart transplantation.
AB  - OBJECTIVE: To evaluate the use of methotrexate for the treatment of recurrent
      rejection in heart transplant recipients. METHODS: We studied 6 patients
      submitted to heart transplantation that showed rejection grade >/= 3A (ISHLT) in
      two consecutive endomyocardial biopsy specimens. The dose was 11.26+/-3.75
      mg/week. The evaluated data were: ventricular function, endomyocardial biopsy,
      white cell count and number of rejection episodes before and after methotrexate
      administration. RESULTS: There was a reduction in the number of rejection
      episodes (5.17+/-1.47 before methotrexate; 2.33+/-1.75 after 6 months and 3.17+/
      2.99 after 12 months of treatment, p=0. 0193). The ventricular function was
      normal with ejection fraction of 76.5+/-4.80 before and 75.6+/-4.59 after
      methotrexate (p=0.4859). One patient did not finish the treatment because he
      showed signs of rejection associated with severe pericardial effusion. Five
      patients had a reduction in the white cell count (8,108+/-23.72 before and 5650+/
      1350 after methotrexate, p=0.0961). One pulmonary infection with complete
      resolution after antibiotic treatment was observed. CONCLUSION: Methotrexate in
      low doses is an effective adjunct therapy in the treatment of recurrent rejection
      after heart transplantation.

PMID- 10904288
TI  - Great amount of C.pneumoniae in ruptured plaque vessel segments at autopsy. A
      comparative study with stable plaques.
AB  - A possible relationship between C.pneumoniae (CP) infection, atherosclerosis and
      acute myocardial infarction is a debated matter. Now we performed the search of
      CP in histological segments of fatal ruptured plaques and of stable plaques by
      histochemistry (Macchiavello stain), immunohistochemistry and in situ
      hybridization techniques. Electron microscopy and confocal laser microscopy
      techniques were used in two additional cases. The semi-quantification of CP +
      cells (0-4+) and quantification of lymphocytes demonstrated greater amount of CP
      + cells and more inflammation in the adventitia of vulnerable plaque vessel
      segments than of stable ones, larger amount of CP + cells in adventitia than in
      the plaque and high frequency of CP + cells in all groups studied. This
      preliminary study strongly suggests a direct pathogenetic involvement of
      adventitial CP in the rupture of the atheromatous plaque, development of acute
      myocardial infarction and also in the development of atherosclerosis.

PMID- 10904289
TI  - Coronary bilateral ostial enlargement using the saphenous vein in a patient with
      syphilitic aortitis.
AB  - A patient with tertiary syphilis presenting with bilateral coronary ostial
      lesions and aortic regurgitation underwent surgical reconstruction of the
      coronary ostia by the anterior approach with autogenous saphenous vein grafting
      and substitution of the aortic valve with a bovine bioprosthesis. The procedure
      was easily performed and had good outcomes both early and late. The rarity of the
      association of a lesion in both coronary ostia with aortic regurgitation in
      syphilis and the surgical technique employed are discussed.

PMID- 10904290
TI  - Clinicopathologic Session. (Case 1/00--a 65-year-old woman with heart failure and
      proteinuria - Instituto do Coracao do Hospital das Clinicas-FMUSP.

PMID- 10904292
TI  - ?

PMID- 10904291
TI  - Coarctation of the aorta corrected during childhood. Clinical aspects during
      follow-up.

PMID- 10904293
TI  - [Seven theses on health education for community participation]
AB  - This article attempts to establish some postulates to orient health education
      aimed at promoting community participation. Theories on human action serve as the
      point of departure for establishing two currents of thought explaining action or
      non-action by people. Two working principles are proposed, i.e., that it is
      necessary to both know and rely on human beings. These two principles are
      expressed in two premises: "Only by knowing individuals and their living
      circumstances is it possible to take efficient and on-going action in health,"
      and "No one can care for someone else's health if that person does not wish to do
      so himself/herself." The author goes on to raise seven theses: 1. There is no
      such thing as one person knowing and another not knowing; rather, there are two
      people who know distinct things. 2. Education is imparted not only through
      educational programs, but in all health-related action. 3. Ignorance is not a
      void to be filled, but a plenitude to be changed. 4. Education should be
      dialogical and participatory. 5. Education should reinforce people's self
      confidence. 6. Education should seek to reinforce the effort-achievement model of
      knowledge. 7. Education should promote individual responsibility and collective
      cooperation.

PMID- 10904294
TI  - [Debate on the paper by Briceno-Leon]

PMID- 10904295
TI  - [Debate on the paper by Briceno-Leon]

PMID- 10904296
TI  - [Debate on the paper by Briceno-Leon]

PMID- 10904297
TI  - [Debate on the paper by Briceno-Leon]

PMID- 10904298
TI  - [Debate on the paper by Briceno-Leon]

PMID- 10904300
TI  - [Debate on the paper by Briceno-Leon]

PMID- 10904299
TI  - [Debate on the paper by Briceno-Leon]

PMID- 10904301
TI  - [Debate on the paper by Briceno-Leon]

PMID- 10904302
TI  - Debate on the paper by Briceno-Leon.

PMID- 10904303
TI  - [The author reply]

PMID- 10904304
TI  - Using the current Brazilian value for the biological exposure limit applied to
      blood lead level as a lead poisoning diagnostic criterion.
AB  - In general, biological exposure limits are only used for the promotion and
      preservation of workers' health and are not applied for diagnostic purposes.
      However, the issue is controversial for certain types of occupational poisoning.
      This paper proposes the utilization of biological exposure limits currently
      applied to blood lead levels in Brazil as an important criterion for diagnosing
      occupational lead poisoning. The author argues that contrary to the traditional
      clinical criterion, one should deal with the diagnostic problem of lead poisoning
      from an epidemiological perspective, using the current Brazilian value for the
      biological exposure limit applied to blood lead level as an indicator of high
      relative risk.

PMID- 10904305
TI  - [Self-reported diabetes mellitus in the city of Sao Paulo: prevalence and
      inequality]
AB  - This report analyzes characteristics of self-reported diabetes mellitus in the
      city of Sao Paulo, Brazil. The data were obtained from the Brazilian Multicenter
      Study on Prevalence of Diabetes Mellitus, a household survey performed in 1986
      88. The Sao Paulo sample consisted of 2,007 individuals aged 30-69 years, of both
      sexes, selected from three areas with distinct socio-economic levels. The
      estimated prevalence using a 75g glucose load and measurement of two-hour
      capillary glycemia was 9.7%. Prevalence of self-reported diabetes was 4.7% and
      increased with age and presence of family history of diabetes. There was a
      significant difference between sexes (3.5% in men and 5.7% in women), with higher
      rates of self-reported diabetes at higher economic levels among men and higher
      rates at lower socio-economic levels among women.

PMID- 10904306
TI  - [Chiral Drugs: from the chemical dimension to political discussion]
AB  - Conceptual aspects regarding chiral drugs are discussed referring to
      enantiomerically pure substances, containing only one isomer, with optical
      orientation to the right (R) or left (S). Impact on world market, that means
      today over US$ 35 billions, or near 20% of total market with chiral drugs, is
      discussed as significative of actual trends. Growing expansion of this matter
      makes us think that there exists a clear trend that will lead chiral drugs to
      represent a new form of market domination, mainly regarding patent protection and
      bypassing crescent generic drug market policies. Finally, the question regarding
      chiral drugs and racemic mixtures is arised, calling attention for the need to
      incorporate this chemical dimension within health policy discussion, also
      considering brazilian capacity in research centers and universities.

PMID- 10904307
TI  - Diet and mortality from common cancers in Brazil: an ecological study.
AB  - A prospective ecological evaluation of mortality from common malignancies with
      dietary risk factors and alcohol consumption was carried out among 10 state
      capitals of Brazil. Regression analysis was used to examine the association of
      dietary intake with mortality rates of the most common cancers among adults age
      30 years and older. Age-adjusted cancer mortality rates varied 2.4 to 3.3 fold
      across the state capitals. A positive relationship was observed between energy
      intake and colon, lung, and esophageal cancer (p</=0.02 for each). Colon cancer
      mortality was positively associated with consumption of total fat, eggs, alcohol,
      mate tea, cereals, and vegetables (p</=0.01). Lung cancer was positively
      associated with mate and cereal intake (p<0.05). Stomach cancer was associated
      with consumption of eggs (p=0.04); and negatively associated with consumption of
      high fiber foods, fruits, and vitamin A and C (p</=0.05). Esophageal cancer was
      positively associated with fat intake, mate and cereals (p</=0.05) and negatively
      associated with vitamin A (p=0.02); prostate cancer was negatively associated
      with vitamin C (p=0.007). Breast cancer was not associated with any of the
      factors studied. The marked variation in cancer mortality rates in Brazil may be
      partially related to the high variation in dietary components or other diet
      associated factors.

PMID- 10904308
TI  - [An education experience for promoting breast-feeding and infant stimulation by
      low-income women: a preliminary study]
AB  - This study included a preliminary analysis of the effectiveness of an educational
      program on breast-feeding and infant stimulation techniques. The program,
      developed by Garcia-Montrone (1992), was applied to a group of mothers
      (experimental group) of low socio-economic status. The program was evaluated by
      direct observation of mother-infant interaction and interviews with the mothers
      up to six months after childbirth. Results were compared with a control group of
      women matched for age, educational level, and previous experience with breast
      feeding. Each group began with 10 mother-infant dyads, and there was one
      withdrawal in each group over the course of the study. 55% of the mothers in the
      experimental group were still breast-feeding six months after childbirth,
      compared to 22% in the control group. The experimental group also showed a
      significantly higher frequency of stimulation of the infant, both during and
      after breast-feeding. The authors conclude that it is feasible to combine breast
      feeding and infant stimulation instruction in an educational program for women of
      low socio-economic status and that the use of this program can help reduce risk
      factors both for malnutrition and developmental retardation.

PMID- 10904309
TI  - [Study of exposure to and health effects of atmospheric metallic mercury
      pollution in an urban population of Pocone, Mato Grosso, Brazil]
AB  - This paper evaluates the levels of exposure to and health effects of metallic
      mercury emissions into the atmosphere by gold dealers in the town of Pocone, Mato
      Grosso State, Brazil. The project was based on the comparison of referred
      morbidity, clinical examination, and metallic mercury urinary concentrations in
      three population groups. The first group consisted of downtown residents who were
      exposed to metallic mercury emissions. The second group resided on the outskirts
      of the town and the third in an agricultural area. Urinary concentrations of
      metallic mercury showed highly significant differences between groups from
      downtown and the outskirts as compared to the control group. Investigation of
      individuals with high concentrations showed that exposure in the downtown area
      might have come from gold dealers' establishments. In the group from the town
      outskirts, exposure might have been from amalgam-smelting done inside homes.
      Referred morbidity data showed an increased proportion of complaints and
      alterations in clinical examinations by downtown residents as compared to the
      other groups.It was concluded that there was a possibility of exposure and health
      effects caused by metallic mercury for residents from the first two groups.

PMID- 10904310
TI  - [Municipalization of vaccination in Ribeirao Preto, Sao Paulo, Brazil]
AB  - The object of this study is the organization of activities in the vaccination
      program in Ribeirao Preto, Sao Paulo, during the process of municipalization of
      health services, analyzing changes and estimating results. The methodology
      included a survey performed during supervisory visits and questionnaires with 20
      nurses and 39 vaccination workers in all the vaccination rooms at the municipal
      primary health care unit in this city, a survey of storage conditions for
      immunobiological products at the municipal level and a questionnaire for the
      section head, and interviews with five health professionals responsible for
      vaccination at the State, regional, and municipal levels. It followed that since
      implementation of the so-called Integrated Health Actions proposal there has been
      an expansion of primary health care services, including vaccination services;
      there has also been a technical and administrative centralization of decisions
      involving vaccination activities, including training of human resources by the
      Municipal Epidemiological Surveillance division. The study points out that
      although this activity is dealt with carefully by those responsible for the
      State, municipal, and district levels, the same is not true at the local level.

PMID- 10904311
TI  - [Serologic survey of dogs in an endemic area of tegumentary leishmaniasis in
      Parana State, southern Brazil]
AB  - Increased reporting of mucocutaneous leishmaniasis in the State of Parana points
      to the need for information on both this disease's epidemiology and pertinent
      control measures. A serological survey was thus performed, with indirect
      immunofluorescence (IIF) for canine leishmaniasis in farm operations belonging to
      the Companhia Melhoramentos Norte do Parana, in Jussara and Terra Boa counties,
      in northwestern Parana. IIF was performed on 132 dogs, of which 24 (18.2%) had
      significant titers (>/=40). Imprints of six dogs with lesions were made and all
      were negative for Leishmania sp.

PMID- 10904312
TI  - [Alternative approaches to the control of schistosomiasis: trying to include
      subjective elements in epidemiology]
AB  - This study discusses the possibility of integrating the "subjective" in
      epidemiological research. Alternative approaches are presented for programs to
      provide health and educational services, as well as others which are the right of
      citizens to receive and the responsibility of the government to provide. The
      characteristics of participatory research, community-based epidemiology, and
      popular education programs are described, with the purpose of constructing a
      model for the control of schistosomiasis using alternative methodologies,
      including in the model the perceptions and life styles of populations exposed to
      Schistosoma mansoni. The Federal Government is indicated as the institution to
      provide the material conditions necessary to form a citizenry with the collective
      will to control schistosomiasis.

PMID- 10904313
TI  - [Molecular genetics: advances and problems]
AB  - This article is an attempt to draw the discussion on molecular genetics in health
      into the public health domain. Now that the genetic engineering revolution has
      arrived, it is important to point out the advances and problems this technology
      poses for society. It is time for a clear, informed assessment of what we have
      already achieved and may soon achieve using this technology. Clearly, society
      needs to understand the ethical and practical implications of a technology which
      can produce miracle drugs and modern diagnoses and cure virtually every disease.
      Important points from sensitive social issues raised by molecular biology and the
      human genome project are discussed.

PMID- 10904314
TI  - [Bioethics in the 1990s]

PMID- 10904315
TI  - Attendance at day care centers increases the risk of childhood pneumonia among
      the urban poor in Fortaleza, Brazil.
AB  - We carried out a case-control study to investigate risk factors for childhood
      pneumonia in two groups of 650 children aged under two years in the city of
      Fortaleza, Ceara, Brazil. The cases were children recruited at the main pediatric
      hospital with a radiological diagnosis of pneumonia, and controls were children
      of the same age group recruited from the neighbourhood of the cases. In this
      paper we focus on variables related to childcare practices. Working mothers,
      proportion of time the mother had worked since the child was born, and use of day
      care centers emerged as important risk factors with estimated relative risks of
      1.58, 1.76 and 5.22, respectively. Also important were the number of children
      living in the house and presence of grandparents. However, the presence of
      siblings under two years and the birth order were not associated with pneumonia.
      All analysis included adjustment for confounding by income, parents' education,
      and other risk factors as appropriate. This is the first study from a developing
      country to identify attendance at day care centers as a risk factor for increased
      childhood morbidity, in this case pneumonia. This finding is of significant
      public health importance for countries such as Brazil with growing urban
      populations and an increasing need by mothers to find work outside the home.

PMID- 10904316
TI  - [Epidemiologic aspects of Cutaneous Leishmaniasis in an endemic area of the state
      of Parana, Brazil]
AB  - An epidemiological investigation of cutaneous leishmaniasis (CL) was performed in
      1992 and 1993 in an endemic area of Jussara and Terra Boa counties, in the
      Northern Parana State. The study covered 684 individuals from a population of
      approximately 1,400 from six agricultural areas (Fazenda Palmital, Ceramica
      Andira, Fazenda Jussara, Fazenda Lagoa, Destilaria Melhoramentos, and Fazenda
      Murure) in Northern Parana, Brazil. The mean frequency of CL history was 19.9%.
      The highest frequency was at Fazenda Jussara (40.5%). Based on the indirect
      immunofluorescence test, 58 (8.5%) presented significant titers of anti
      Leishmania antibody, 17 (29.3%) of whom had no history of CL. The Montenegro skin
      test was applied to 97 individuals with a history of CL and was positive in 80
      (82.5%). During the survey, seven individuals presented lesions, four of which
      were positive for Leishmania sp. The strain isolated was identified as Leishmania
      (Viannia) braziliensis.

PMID- 10904317
TI  - [Methodology to prevent mercury exposure among adolescents from goldmine areas in
      Mariana, state of Minas Gerais, Brazil]
AB  - The main objective of this study was to promote the evaluation of an educational
      method to identify health risks among adolescents exposed to mercury by their
      work in gold mining production.The project was carried out with adolescents from
      a public school from the District of Monsenhor Horta, Municipality of Mariana,
      state of Minas Gerais. Statistical evaluation of the results revealed a
      significant increase in the amount of correct answers between the first and fifth
      stage concerning the definition of work accidents and its importance in relation
      to work-related diseases, accidents on route to and from the work place and
      violence at work site itself.

PMID- 10904318
TI  - [Controlling the indiscriminate use of medical technologies and the rise in the
      costs of health care: the German strategy]
AB  - In view of reforms implemented in health care systems in many countries, both
      developed or developing, and especially in view of the implementation of the
      Sistema Unico de Saude - SUS (Single Health System) in Brazil, the author
      presents some aspects of the reform process in the German Health Care System.
      Special attention is given to the various mechanisms employed in Germany to keep
      health care costs stable in the system in relation to the Gross Domestic Product
      (GDP), mainly through the adoption of measures to rationalize use of medical
      technologies. Some aspects related to the broad bargaining process between the
      Medical Boards and the funds providing health care services are discussed, with a
      view towards elaboration of parameters for assessing medical performance,
      particularly in relation to utilization of medical technological resources.
      Finally, the author briefly discusses the impact of such measures in producing
      changes in medical performance standards.

PMID- 10904320
TI  - [Basic sanitary systems and social inequalities in the Rio de Janeiro
      metropolitan area]
AB  - This article deals with the distribution of financial resources allocated to the
      basic sanitary systems in the Rio de Janeiro metropolitan area during the 1975
      1991 period. The study analyzes the investments allocated by the local utility
      company, known as Cedae, using a spatial model produced especially for this
      research. The model was produced using information from the national demographic
      census of 1980, the only one developed within the study period. The recent
      changes as observed are explained on the basis of their relationship to the
      spatial and political contexts in the metropolis and the country, as well as from
      the organization of the services themselves. The paper adds important arguments
      to the discussion over the restructuring of metropolitan areas and urban public
      policies. The spatial and social distribution of resources observed during the
      period differed from the preexisting pattern, yet although there was a
      substantial democratization in the allocation of public resources, the pattern
      was not subverted.

PMID- 10904319
TI  - [Alcohol-related disorders in a psychiatric emergency service. Ribeirao Preto,
      Brazil]
AB  - This study reports the results of a survey carried out in the psychiatric
      emergency service of the University Hospital of Ribeirao Preto, Brazil (1988
      1990) with the purpose of characterizing psychiatric disorders related to the
      consumption of alcohol. The sample included data on a total of 1,082 patients
      diagnosed during this period. A total of 576 cases were diagnosed with "alcohol
      dependency syndrome", 379 with "alcohol psychosis", and 127 patients with
      "alcohol without dependency". The majority of patients were male and the age
      group most affected was 25-44 years for both sexes. The study calls attention for
      the importance of alcohol abuse as a public health problem.

PMID- 10904321
TI  - [Ecology of sandflies in Serra do Mar, Itaguai, state of Rio de Janeiro, Brazil.
      I - Sandfly fauna and prevalence of the species in collections sites and method
      of capture]
AB  - A two-year investigation was conducted in Itaguai, State of Rio de Janeiro, an
      area with cases of cutaneous leishmaniasis, in order to study the ecology of
      sandflies and their habits and role as parasitic vector for men and animals.
      Capturing took place at three sites: domiciliary (human bait, walls, and light
      traps); peridomiciliary (walls, from baits used simultaneously: humans, dogs, and
      chickens; and light traps); and sylvatic (human bait and light traps). A total of
      10,172 sandflies were captured, belonging to 17 species of genuses Brumptomyia
      Franca & Parrot, 1921 and Lutzomyia Franca, 1924. L. intermedia was predominant,
      100 m above sea level, as compared to L. migonei and L. fischeri. In a drier area
      300 m above sea level L. migonei was prevalent, followed by L. longipalpis and L.
      fischeri. The species which presented the greatest endophily was L. fischeri,
      showing a certain degree of eclecticism regarding the biting site. L. intermedia
      and L. migonei proved to be more exophilic. L. intermedia was considered to be
      potentially the main transmitter of the disease because of its prevalence,
      anthropophily, and the fact it is known to be a vector of Leishmania (V.)
      braziliensis in other areas of the Southeastern region of Brazil. L. fischeri,
      because of its anthropophily, might also be involved.

PMID- 10904322
TI  - [Problems and limits in the utilization of the concept of social class in
      epidemiologic research: a critical review of the literature]
AB  - The application of inductive empirical variables in hegemonic alternatives of
      Epidemiology in order to treat socioeconomic variations in human groups has
      displayed certain limitations raising the need for new proposals. The use of
      social class was thus introduced as an analytical category operated according to
      place in the productive process for the subjects under study. This choice has
      already shown potentialities in several studies. This paper was intended to
      identify some limits and problems occurring when using the social class concept
      in epidemiological research. Besides the need for an adequate theoretical
      framework, construction of categories consistent with both their theories and the
      levels of abstraction employed, and the concern for more carefully analyzing the
      consumer and working modes for each social class (questions that have been
      discused elsewhere), this paper approaches several issues, as follows: the
      treatment of social classes as articulated clusters in the research process, the
      need to adjust the operational scheme to the particularities of each
      socioeconomic formation, the simplification resulting from the process of
      reducing the concept of social class to several linked variables, the need for a
      relatively large sample, the existence of debate over the definition of the
      position of class groups not participating in production, and subjects with two
      or more different positions in production.

PMID- 10904323
TI  - [Analysis of neonatal tetanus mortality in Brazil]
AB  - This study reports mortality from neonatal tetanus in Brazil (1979-1987), based
      on an analysis of death certificates. The distribution of causes of death in time
      and space was used as an indicator of proportional neonatal mortality from
      tetanus. Underreporting remains a serious problem, particularly in northern and
      northeastern Brazil. In most municipalities, only one death was notified during
      the period under consideration, thus highlighting the importance of considering
      the theoretical approach of "sentinel events" in the control of this disease. A
      proportional decrease in mortality from neonatal tetanus was observed in the
      states of Rondonia, Para, Sergipe, Sao Paulo, Parana, and Rio Grande do Sul. It
      was not possible to detect an association between immunization coverage with two
      doses of tetanus toxoid and neonatal tetanus mortality. The reduction in the
      number of deliveries taking place in the home during the period studied appears
      to have played an important role in the reduction of neonatal deaths attributable
      to this cause.

PMID- 10904324
TI  - [A socioeconomic characterization of leprosy patients at the dermatology clinic
      in Maracaibo, Venezuela: a case study]
AB  - This paper presents the socioeconomic characteristics of leprosy patients treated
      at the Dermatology Clinic in Maracaibo, Venezuela (U.D.S). The characteristics
      were obtained from a closed questionnaire given to 40 patients. Results indicate
      that this is mainly an adult male population, with a reasonable level of
      schooling who both work and belong to apparently well-established, stable family
      groups; their family income levels correspond to a lower or medium-low social
      class groups. In addition, the patients are mainly non-disabled, and clinical
      diagnoses are mostly of the lepromatous and borderline types. Any educational
      program targeting this group should take these socioeconomic characteristics into
      account in defining the kind of patients who receive treatment at U.D.S.

PMID- 10904325
TI  - [Accessibility to health services by HIV-infected patients: a literature review]
AB  - The aim of this paper is to provide a review of studies on accessibility to
      health care. It has been shown that patients infected by the human
      immunodeficiency virus (HIV) may present better survival estimates depending upon
      their access to adequate health care, such as the availability of prophylactic
      therapy (e.g. zidovudine, pentamidine). The present review has emphasized access
      to health care in light of data from the current HIV epidemic. Theorical aspects
      pertaining to accessibility are presented, followed by a brief literature review
      on four main topics: 1. epidemiological aspects of HIV; 2. evaluation of health
      service quality; 3. accessibility to health care; and 4. accessibility studies on
      HIV-infected patients. Final considerations indicate the need to understand the
      various consequences of barriers to health care, taking into account the social
      and human costs of HIV infection, the needs and demands of HIV-infected patients,
      and the consequences of delays in care for these individuals.

PMID- 10904326
TI  - [Evolution of neonatal mortality in the state of Rio de Janeiro, Brazil]
AB  - This paper reports the results of a study on neonatal mortality in the State of
      Rio de Janeiro (1979-1993), according to major causes of death, by age and region
      of residence. The authors suggest criteria for grouping neonatal deaths according
      to causes, taking into consideration frequency and preventability. For deaths
      which occurred in the first day of life, immaturity and fetal growth retardation
      were the only causes of death that showed significant decline. An increase in
      deaths due to respiratory affections of the fetus and newborns was observed.
      Causes of death said to be reducible by "adequate control of pregnancy and
      attention at delivery" and "early diagnosis and treatment" remained unaltered.
      The authors noted that a decrease in death rates took place starting with the 1-6
      day age group. The comparison with other countries called attention to the high
      rates of neonatal death in Rio de Janeiro. It also pointed out an increase in the
      proportion of deaths classified as "respiratory problems of the newborn",
      demonstrating lack of specificity in defining the basic cause of death.

PMID- 10904327
TI  - [Physical growth in stature of school children of Japanese ancestry in the city
      of Sao Paulo, Brazil]
AB  - This paper reports the results of a cross-sectional survey describing the growth
      in stature of a sample of school children of Japanese ancestry (three or four
      grandparents born in Japan) and of high socio-economic status living in Sao
      Paulo, Brazil. The sample comprises 124 individuals 7-10 years of age, of both
      sexes. The results show that the children present mean values of stature below
      the median values of the NCHS curves ("National Center for Health Statistics",
      U.S.A.). The values are similar to the medians of a sample of Japanese children
      and below those of well-to-do Brazilian children of non-Japanese ancestry studied
      by the PNSN ("Pesquisa Nacional sobre Saude e Nutricao", Brazil). The findings do
      not support the hypothesis of uniformity of growth potential in stature, casting
      doubts on the utilization of a single anthropometric reference in the assessment
      of nutritional status.

PMID- 10904328
TI  - [The discussion on induced abortion in the Brazilian Congress: the role of the
      women's movement]
AB  - Induced abortion has been discussed in Brazil for many years without producing
      changes in the Penal Code in force since 1940 and according to which it is
      illegal and a crime against life. There are only two circumstances in which
      induced abortion is allowed: when there is no other recourse for saving the
      pregnant woman' life, and when the pregnancy resulted from rape and the abortion
      is preceded by the woman's informed consent. The purpose of this article is to
      show how the abortion problem has been dealt with under executive and legislative
      policies, focusing especially on discussion in Congress considering the role of
      organized women's groups. The study focuses on the legislative debate on induced
      abortion and how it was preceded, accompanied, and followed by actions by the
      women's groups. Other political and social actors involved in the debate, such as
      the Catholic Church, sectors of the medical community, and protestant religions
      are mentioned.

PMID- 10904329
TI  - [Health information systems at the local level]
AB  - Information systems have assumed paramount importance in modern society, becoming
      an strategic resource of power in all areas. Therefore, it is important that the
      process of decentralization of the health sector should not be limited to
      services, but should also consider the decentralization of information. The
      author discusses the sharing of political and technical responsibility between
      various governmental spheres, and the need to rethink and redirect the process of
      making accessible information on health. This is a matter of overcoming vertical
      relations between government and society and of moving toward cooperative
      management capable of minimizing regional inequalities and optimizing the
      utilization of resources.

PMID- 10904330
TI  - [Editorial]

PMID- 10904331
TI  - Duration of day-care attendance and acute respiratory infection.
AB  - Day-care attendance accounts for an increased frequency of acute respiratory
      infections (ARI), in numbers of both episodes and hospitalizations. In addition
      to day-care exposure, risk factors include age, siblings, and crowding. The
      purpose of this study was to investigate a possible association between duration
      of day-care exposure and ARI. A cross-sectional study was carried out to compared
      ARI rates for children exposed to day care and children cared for at home.
      Children with at least one parent working in a hospital were sampled from the
      hospital-run day-care center and those cared for at home. An acute respiratory
      infection was defined as the presence of two or more signs or symptoms in the
      previous two weeks. Children exposed to the day-care center for 12 to 50 hours a
      week had a three to five times greater risk of developing ARI than those staying
      at home. This risk was assessed independently, taking socioeconomic status, age,
      and number of siblings into account. Risk of respiratory illness and day-care
      attendance has been described elsewhere, but this study presents original
      findings related to duration of exposure. With a view towards reducing risk of
      ARI, improvements should be made in institutional day-care centers in Brazil,
      where family day care is still not available.

PMID- 10904332
TI  - [Work and common disease in a pulp and paper industry: a profile by department]
AB  - The purpose of this study was to identify associations between common morbidity
      and work accidents and the respective departments in a pulp and paper industry,
      describing work loads and performing broad control of potential confounding
      factors. We studied all the workers from a specific pulp and paper industry,
      using a cross-sectional design and interviews at the workplace (n=671) with a
      standardized questionnaire. We characterized workers' perceptions of their
      occupational exposures and health problems. The industrial area had an excess in
      auditory problems (OR>2.5) and respiratory problems (OR>2.7) as well as accidents
      (OR>4.7). These diseases were probably related to the high prevalence of noise,
      dust, sudden temperature changes, exposure to various chemicals, and excessive
      effort and high-risk situations. Moreover, the management group showed an excess
      in eye problems, backache, irritation, and nervousness (OR>1.7), apparently
      related to lack of autonomy and creativeness at work, ergonomic problems, and
      strained eyesight. The study confirmed not only a high prevalence of common
      diseases, but also their relationship to specific features of the work process
      indicated by each department category.

PMID- 10904333
TI  - [Sampling and representativeness in epidemiological surveillance using sentinel
      sites]
AB  - This article maintains that technical issues for sampling in epidemiological
      surveillance require a profound review of important concepts from health theory.
      It is particularly neccessary to emphasize living conditions and more
      specifically the environments or contexts in which reproductive processes of
      social life take place. However, both fields require access to more complete data
      than those produced by traditional sources. Such an approach to epidemiological
      surveillance requires a review of sampling types, and this implies a new look at
      prevailing interpretations concerning the logical basis for inferences from
      samples. It becomes necessary to abandon statistical samples (even stratified
      ones) and to promote procedures of the "sentinel site" type. This techinique,
      originally applied in societies with insufficient statistical systems, can be
      developed in such a way as to become a substantial complement to monitoring of
      living conditions, even in societies with good information systems. The article
      suggests changes in the "sentinel site" concept, adding the requirement of
      "qualitative representativeness" through finalistic samples based on previous
      typologies of spatial/demographic units.

PMID- 10904334
TI  - [Canine cutaneous and visceral leishmaniasis and Chagas' disease from counties in
      the Triangulo Mineiro and Alto Paranaiba regions, Minas Gerais State, Brazil]
AB  - Leishmaniasis and Chagas' disease were surveyed by indirect immunofluorescence
      with sera from 331 dogs from Uberlandia and Coromandel, two counties in the State
      of Minas Gerais, Brazil. Leishmania amazonensis and Trypanosoma cruzi antigens
      were employed. In Uberlandia county, 230 sera were studied, of which 200 were
      from urban areas and 30 rural: 4.5% of urban samples and 6.6% of rural were
      positive for L. amazonensis antigen. Of 89 sera from Coromandel, 5.6% were
      positive for the same test to L. amazonensis antigen. Twelve additional canine
      sera were obtained from the Veterinary Hospital at the Federal University in
      Uberlandia, all of which with a pending diagnosis of leishmaniasis: of these, one
      had a positive immune test to L. amazonensis and another to T. cruzi antigens.
      The results suggest regional urbanization of both leishmaniasis and Chagas'
      disease in the canine populations of both communities.

PMID- 10904335
TI  - [Differences between proposals for implementation of the social class concept in
      epidemiological studies]
AB  - This article compares different proposals for the implementation of the concept
      of social class and analyzes the alternatives used in each proposal, considering
      previous epidemiological studies on this issue and the potential of such a
      concept as a central category in studies on social determination in the
      health/disease process. Seven basic differences were identified, pertaining to
      the following aspects: class structure; research objective; the social class
      concept as a reference; the decision as to which individual has his/her
      occupational activity taken as defining the family's social class; the class
      status of the unemployed, housewives, and the retired; class status of students;
      and criteria for distinguishing between the "bourgeoisie", "petty bourgeoisie",
      "new petty bourgeoisie", and "proletariat" and whether there is a specific flow
      in certain population groups. Given the observed differences and underlying
      theoretical models, this study discusses problems related to the fact that the
      use of a specific concept of social class can have various implementation models.

PMID- 10904337
TI  - [The ethical dilemmas of human life: the hospital history of children with
      serious cerebral palsy]
AB  - This study deals with the ethical premises of medical treatment for children with
      serious cerebral palsy. Eight months of ethnographic research were carried out
      with patients at the Cerebral Palsy Center in the Sarah Hospital in Salvador,
      Bahia, Brazil. Observation of treatment for these children, who displayed limited
      clinical change, led to the following question, as suggested by discussions from
      medical deontology: What is the purpose of medical treatment for children with
      serious cerebral palsy? The results of our research point to social and humanist
      explanations going beyond the official medical scientific explanation, which
      limits treatment to corporal mechanicism.

PMID- 10904338
TI  - [Situational management]
AB  - In this paper, the organizational theory of situational planning is used to
      establish a decentralized management model for complex health units. Because of
      cultural limitations imposed on a perspective of change and rationalization,
      considerations are made in relation to a given form of dealing with culture,
      keeping in mind the feasibility of the management model. A particular type of
      communicative management emerges as a general need revealed by the analysis of
      the object at issue: the management of professional organizations.

PMID- 10904339
TI  - [Peasant strategies for economic reproduction and malaria epidemiology in the
      ravines microregion of the Chiapas mountains, Mexico: a case study]
AB  - The goal of this investigation was to establish an initial correlation between
      farming activities and malaria and to define risk factors and prevalence of the
      latter through an analysis of the integration of farm production strategies by
      members of an indigenous peasant community in the Chiapas mountains in Mexico.
      Information was obtained on places of work, land use, coffee, corn, and bean
      farming, and number of family members involved in farming activities, wage labor,
      and handicrafts production. Migration of farm workers to warmer climates was also
      analyzed. The study compared families with and without cases of malaria from 1987
      to 1993 in the town of Yibeljoj, Chenalho county. The most outstanding
      characteristics of this analysis were the following: strategies involving greater
      risk and prevalence of malaria were those which combined corn farming and wage
      labor; on the other hand, strategies in which handicraft production was the
      activity of primary or secundary importance were associated with few or no cases
      of the disease.

PMID- 10904340
TI  - [Enteroparasitosis in pregnant and post-partem women in Rio de Janeiro]
AB  - From November 1989 to May 1991, in Rio de Janeiro, Brazil, the prevalence of
      intestinal parasitosis was investigated in 795 women coming from the Public
      Health Services, who were divided into three groups: 490 pregnant women in pre
      natal care period, 104 after-delivery women and 201 non-pregnant women (control).
      Coproparasitologic tests were run using the Sedimentation through Centrifugation,
      Faust, Kato-Katz and Baermann-Moraes methods. Positivities were found ranging
      from 37.6% to 53.6% for pregnant women, 38.3% for non-pregnant women and 69.2%
      for after-delivery women, with statistically significant differences between the
      rates of pregnant women and after-delivery women, and with no statistic
      difference between the groups of pregnant and non-pregnant women. The most
      frequent parasites found were A. lumbricoides and T. trichiura. The conclusion
      was that the control of intestinal parasitosis is not a priority in the pregnant
      population studied because, in spite of the regular assistance provided during
      the pre-natal care period, they keep on infected.

PMID- 10904341
TI  - [Are geoprocessing, environment, and health a possible combination?]
AB  - The use of geoprocessing techniques allows one to gather socioeconomic, health,
      and environmental data on a spatial basis. However, interpretation of
      associations between epidemiological and environmental variables requires the
      geoprocessing system design. The study scale and object choices precede
      conception of the system, conditioning the possible statistical and visual
      results. This scale must be compatible with the phenomenon on which one intends
      to focus, aiming at internal homogeneity and external heterogeneity of spatial
      units. The interdependency of spatial processes, reflected in the spatial
      configuration of social, environmental, and epidemiological data distribution,
      affects interpretation of causes for simultaneous processes. Geoprocessing allows
      for knowledge of the context or situational surroundings in which the damage to
      health takes place.

PMID- 10904342
TI  - [Towards a strategy for quality assurance: satisfaction in the utilization of
      medical care]
AB  - This study aims to develop methodological tools to assess and guarantee quality
      of medical care by investigating satisfaction of expectations by objects of care
      (patients), medical institutions (directors), and direct providers of care
      (health personnel). The perspectives of this analysis included the structure,
      process, and outcomes of medical care. Perhaps the novelty of the research is its
      democratic approach, i.e., the three main protagonists' freedom of expression
      regarding medical care and the questioning of such aspects as individual, social,
      and professional satisfaction and the work environment, ultimately leading to the
      humanization of the work and thus to quality of care.

PMID- 10904344
TI  - [Prevention and treatment of iron-deficiency anemia: new focuses and
      perspectives]
AB  - The authors briefly describe the epidemiology of anemia, the goals established by
      the United Nations to combat the problem worldwide, and the difficulties
      encountered in applying proven effective strategies in public health services to
      prevent and cure anemia in pregnant women and children, both of which are prime
      high-risk groups. They analyze recent research aimed at four objectives related
      to prevention and cure: improving treatment efficacy; increasing effectiveness;
      reducing costs; and decreasing unwanted side effects. The study indicates that
      ongoing research could improve prospects for treatment through public health
      services.

PMID- 10904345
TI  - [Ethics and biomedical research in Amerindian societies in Brazil]
AB  - This paper discusses the ethics of biomedical research in Amerindian populations
      of Brazil, focusing on the obtainment of informed consent in field work involving
      the collection of biological samples. The authors emphasize that the current
      legislation does not specifically regulate biomedical research in these
      populations. From an anthropological standpoint, the authors discuss some of the
      difficulties in obtaining a "truly" informed consent. The relevance of the
      discussion on research ethics is of growing importance due to the possibility of
      commercial use of human biological samples, as illustrated by the ongoing debate
      on the granting of patents to human genetic materials.

PMID- 10904346
TI  - ?

PMID- 10904347
TI  - [In search of a national forum for bioethics in Brazilian public policy]
AB  - This article focus on bioethics as a public policy issue. It analyzes the main
      existing international codes on biomedical ethics and presents a brief review of
      the work of some national bioethics committees in developing countries. The
      author concludes by commenting on the most relevant and controversial aspects to
      be considered in the Brazilian experience.

PMID- 10904348
TI  - [Readjustment of the biological exposure limit applied to blood lead levels in
      Brazil]
AB  - We randomly selected twenty lead workers from an electric accumulator factory in
      the State of Sao Paulo, Brazil, whose blood lead level and urinary d
      aminolevulinic acid level were below 60 mg/dL and 10 mg/L, respectively. The
      workers were submitted to a standard motor nerve conduction velocity study of the
      right radial nerves, in addition to blood lead dosage. Based on these measures, a
      first-order linear regression model was adjusted, where the dependent variable
      was conduction velocity and the independent variable was the blood lead level.
      Analyzing the fitted model, we inferred that the negative predictive value of the
      Brazilian biological exposure limit is 0.63. In order for the above biological
      exposure limit to have a negative predictive value of 0.99, the study suggests
      that it be reduced from its present value (60 mg/dL) to 32 mg/dL.

PMID- 10904349
TI  - [Eco-epidemiological aspects of American cutaneous leishmaniasis in the
      Municipality of Campinas, Sao Paulo, Brazil]
AB  - The authors describe an outbreak of American cutaneous leishmaniasis from
      February 1993 to September 1994 in the districts of Sousas and Joaquim Egidio,
      Campinas, Sao Paulo State. Out of a total of 25 cases, seven occurred in the
      countryside, nine in the periurban area, and nine in the urban area. The authors
      observed a shift in the occurrence of leishmaniasis cases from rural to urban
      areas. Cases in males predominated over females (60%/40%). Some 44% of the cases
      occurred in individuals ranging from 11 to 30 years of age. Some 48% of cases
      occurred in students, domestic workers, and housewives. In 90% of the cases, the
      disease presented as a single lesion, located predominantly on the upper and
      lower limbs. The appearance of cases in the region is probably related to the
      expansion of urban areas occurring in the 1970s and 1980s, a trend which
      intensified further more recently.

PMID- 10904350
TI  - [Integrated control of the filariasis vector with community participation in an
      urban area of Recife, Pernambuco, Brazil]
AB  - A pilot study for the control of Bancroftian filariasis transmission was
      developed in two areas of Recife, Brazil, where microfilaraemic prevalence was
      10% in 1991. Mass treatment with diethylcarbamazine (DEC) using low and spaced
      doses was employed in both areas. In one such instance, DEC therapy was
      associated with vector control using physical measures and periodic treatment of
      Culex breeding sites with the entomopathogen Bacillus sphaericus. The vector
      population density, reaching 60 - 120 Culex/room /night before the intervention,
      was drastically reduced to 4 - 16 Culex/room/night, and maintained at this level
      for more than two years. Actions to engage the local school community in the
      vector control process were implemented, and as a consequence several classroom
      and extracurricular activities were put into practice, culminating with the
      effective participation of a team of students called the "Vector Vigilantes", in
      the application of control measures against the vector. The enthusiastic
      involvement of schoolteachers and students pointed to schools as a place amenable
      to programs such as this.

PMID- 10904352
TI  - [The common-sense knowledge and its implication for the occupational health
      surveillance]
AB  - This article deals with Occupational Health Surveillance as a health action
      induced by the workers' knowledge. In order to develop this conception, it adopts
      the notion of Health Surveillance, especially the concept of problem, and the
      notion of common-sense knowledge under the perspective used by social psychology.
      Supported by these considerations, we assume that the formulation of a health
      problem is a social representation. These considerations are used to examine the
      practice of "workers' investigations" as conceived by the Italian experience,
      pointing to its implications for the formulation of problems and identification
      of strategies in order to act on its determinants.

PMID- 10904351
TI  - [Designing criteria to handle diabetes patients as a strategy for quality
      assurance]
AB  - This study was carried out at the General Hospital of Zone N masculine 14 of the
      IMSS in Jalisco, Mexico, with the goal of designing standardized criteria to
      handle hospitalized diabetes patients, as a strategy for quality assurance,
      through the participation of a panel of experts in internal medicine from the
      hospital. Participation by the attending physician in designing criteria
      generates a sense of belonging in the staff and makes adherence and application
      easier. The suggested criteria are subject to further improvement and are not
      intended for universal application, but to the extent that they have been useful
      in patient care they have far surpassed the authors' expectations when the goals
      of this research were originally established.

PMID- 10904353
TI  - [Obstacles to compliance with treatment for Hansen's disease]
AB  - This research project aimed at identifying some of the factors related to leprosy
      patient compliance with the multidrug treatment regimen. The methodological
      framework of the Social Representations Theory was used. Two groups of patients
      were interviewed: compliant and non-compliant with treatment and those coming
      from two different health services. We observed a common understanding about
      treatment in the various interviews, expressed as a metaphor to describe the
      treatment experience: the figure of a battle in which the bacillus is portrayed
      as a threat, the patient as a victim, the medication as a weapon and the health
      professional as a hero or saint. Still, the medication is represented as being
      both good and bad for the patient's well-being. Finally, quality of the physician
      patient relationship appeared to be the main difference between the two groups of
      subjects studied.

PMID- 10904354
TI  - [Epidemiological analysis of pediatric tuberculosis in the city of Rio de
      Janeiro]
AB  - With the purpose of studying the epidemiological situation of pediatric
      tuberculosis in Rio de Janeiro, we analyze the reporting forms for 560 patients
      under 15 years of age, among those being monitored by the city Tuberculosis
      Control Program. The following variables were studied: age, clinical form,
      results of laboratory tests, and places where the patients were seen. About 96%
      of the data investigated was found. The main results were the following: 1. the
      relative percentage of cases among children compared to adults was similar in Rio
      de Janeiro (6.6%) and Brazil (6.7%); both were far below the percentage expected
      by the Brazilian Ministry of Health; 2. 70% of cases presented with the pulmonary
      form of the disease; among these, microscopy was performed in 50%, with 29% of
      positive results; 38% of the patients displayed radiological lesions, with signs
      of cavitation; 3. only 24% of the case contacts were controlled; 4. incidence
      rates of all forms of tuberculosis in Rio de Janeiro were much higher (as much as
      62.6 times higher for some coefficients) as compared to Brazil as a whole; and 5.
      prevalence of positive serology for HIV was at least 4.1%.

PMID- 10904355
TI  - [Evaluation of environmental contamination and pollution at the area under the
      influence of the Morro do Ceu landfill dump in Niteroi, Rio de Janeiro, Brazil]
AB  - In general, areas used for waste disposal represent potential foci of
      environmental pollution, as they can contaminate the surrounding environment and
      negatively impact the health of the populations living nearby. This study reports
      on results obtained in the analysis of Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn in the
      leachate and other environmental compartments (ground and subsoil waters, soil,
      and sediments) of an area under the influence of the Morro do Ceu Landfill Dump,
      located in Niteroi, Rio de Janeiro State, Brazil. Quality of water compartments
      in the area was evaluated using other physical/chemical and microbiological
      complementary parameters such as COD, BOD, pH, colimetry, etc. Results showed
      that most of the metals are retained by the soil and sediments. The local waters
      (surface and subsoil) are contaminated by coliform, while the surface water, the
      Mata-Paca River, showed high levels of COD (5.200 mg/l), BOD (2.800 mg/l), Fe
      (6.4 mg/l), Mn (2.4 mg/l), Ni (0.12 mg/l), and Zn (0.23 mg/l).

PMID- 10904356
TI  - [Nutritional practices in type II diabetic patients in primary care. Mexican
      Social Security Institute]
AB  - Nutritional practices of diabetics reflect both human behavior and the health
      culture of such patients. They also represent how the diabetic deals with the
      health/illness issue. The purpose of this survey was to identify and relate
      nutritional practices with metabolic control, age, sex, years of schooling, and
      time since diagnosis of illness. The sample was taken from 114 cases selected
      through systematic random sampling in five family practice units in Guadalajara.
      Using thirteen structured, coded, and quantified questions of the Likert type,
      the study evaluated nutritional practice with a range of 0-65. Results showed
      that 21% of the diabetics had appropriate nutritional practices (>31 points), and
      when related with years of schooling and time since diagnosis of illness, they
      showed statistically significant differences (p=0.05). Simple regression showed
      that 9% of metabolic control can be explained by nutritional practices.

PMID- 10904357
TI  - [The right to health from the point of view of members of a local health council]
AB  - Based on a qualitative methodology using interactive techniques (in-depth open
      interviews), this study discusses both the concept of the right to health and
      potential ways to claim this right from the point of view of a group of full
      members of the Local Health Council in the City of Sao Paulo during the 1993-1996
      term. The study also interprets a number of issues related to "health advocacy",
      a potential locus of support and advice for groups working to improve health
      conditions for the population.

PMID- 10904359
TI  - [Preliminary check list of species from the genus Lutzomyia, Franca, 1924]
AB  - This paper presents a preliminary check list of Lutzomyia species from Maranhao
      State. The information derives from data gathered in the scarce literature on the
      distribution patterns of neotropical phlebotomines. There are 40 species reported
      in the State. Most are Amazonian in their distribution, while others come from
      the savanna domain of Central Brazil or have a widespread distribution in the
      neotropics. This can be explained by Maranhao's transitional position between the
      North, Northeast, and Central South of the country. Of the species of sandflies
      reported, seven are currently considered vectors for cutaneous and visceral
      leishmaniases.

PMID- 10904358
TI  - [Schistosomiasis: new occurrence of Biomphalaria straminea in Belo Horizonte,
      Minas Gerais]
AB  - In Belo Horizonte, Minas Gerais, Brazil, the snail Biomphalaria straminea was
      found in the Pampulha region. Recently the snail was found in ditches in the old
      Santa Lucia Reservoir, a now-extinct focus of schistosomiasis transmission by B.
      glabrata. The snails were collected and examined to verify whether they were
      naturally infected with Schistosoma mansoni. Negative specimens were used for
      breeding or infection with the LE strain of S. mansoni from the laboratory and
      another strain obtained from eggs found in the feces of a schoolchild (VGS) from
      Belo Horizonte. Among the 1890 snails collected from 1994 to 1995, none were
      infected with S. mansoni. Among 87 snails collected and exposed to the LE strain,
      9 (10.3%) shed cercariae; among 83 snails from F1, and exposed to LE, 10 (12.0%)
      shed cercariae. Among 88 snails exposed to VGS, 10 (11.3%) shed cercariae. In
      Belo Horizonte, schistosomiasis is transmitted by B. glabrata and B. tenagophila.
      However, currently there exists the risk of appearance of a focus in which B.
      straminea could be the host if prophylactic measures are not taken by the
      authorities responsible for the construction of a park and lake at that site.

PMID- 10904360
TI  - Influence of the copepod Mesocyclops longisetus (Crustacea: Cyclopidae) on the
      survival of Vibrio cholerae O1 in fresh water.
AB  - In an experimental microcosm, an analysis was performed of the influence exerted
      by freshwater Mesocyclops longisetus copepods on the survival of Vibrio cholerae
      O1 serovar Inaba. In the State of Ceara, copepods are used in the control of
      Aedes aegypti larvae. The system consisted of water with a salinity of 0.27 per
      10,000 habitants and pH 7.5, which after sterilizing filtration was distributed
      into seven flasks with a volume of 400 ml; in each of six flasks, 10 live
      copepods were inoculated along with 1 ml of an 8-hour culture of Vibrio cholerae
      O1 at 37oC in Alkaline Peptone Water, resulting in a concentration of 3.80x10(4)
      colony-forming units. The control flask contained only the water with the same
      bacterial suspension. The system was maintained for six days at room temperature
      (25-28oC), and daily duplicate counts were performed in TCBS Agar. Results
      confirmed a clear association between Vibrio cholerae O1 and the live copepods,
      based on survival of the bacteria at compatible levels with the initial
      inoculation until the sixth day of the analysis.

PMID- 10904362
TI  - ?

PMID- 10904361
TI  - [Clinical epidemiology: a new medical ideology?]
AB  - In this work we discuss the emergence of Clinical Epidemiology with its doubly
      ideological nature. We begin by presenting different connotations of ideology,
      two of which are chosen to be discussed here. The first is the positivistic
      concept of ideology as the set of ideas of a given historical time; the second is
      the Marxist concept of ideology, as concealing relations of dominance. Under the
      first meaning, Clinical Epidemiology is discussed vis-a-vis ideas in force in the
      1980's, giving it a predominantly post-modern character along with the load of
      individualism born by this word. Finally, we present the myths underlying
      Clinical Epidemiology, seen now according to the second meaning of ideology.

PMID- 10904364
TI  - [Socioeconomic situation and living conditions: comparison of two population
      based cohorts from southern Brazil]
AB  - Socioeconomic and family characteristics of two cohorts of babies born in 1982
      and 1993 in Pelotas (Southern Brazil) were compared. There were 6,011 births in
      1982 and 5,304 in 1993. In relation to family income, there were fewer poor
      babies in 1993; 60.8 % of the families earned less than 3 times the monthly
      minimum wage in 1993, as compared to 69.5% in 1982. Sanitary conditions also
      improved over the decade, and the proportion of families with running water and
      flush toilets increased by 10%. On the other hand, there were no changes in the
      proportion of single-parent families or availability of home appliances like
      radios, stoves, and refrigerators. The mean number of persons per household
      increased from 3.0 in 1982 to 3.2 in 1993. In general, comparison of the two
      birth cohorts in this city suggests an improvement in quality of living over the
      time period for families with newborns. This finding should be taken into account
      when studying the evolution of health indicators over the course of the decade.

PMID- 10904368
TI  - [Breastfeeding and feeding patterns in two cohorts of children in southern
      Brazil: trends and differences]
AB  - Breastfeeding is fundamental for infant health. However, its median duration in
      Brazil is very short, and national campaigns since the mid-1980s have attempted
      to revert this situation. In the present paper, data on breastfeeding are
      compared for two population-based cohorts of children born in 1982 and 1993 in
      the city of Pelotas in Southern Brazil. All hospital births in both years were
      studied and samples of these children were visited at home around 12 months of
      age. Median duration of breastfeeding increased from 3.1 to 4.0 months in this
      period. This rise suggests an impact by the national campaigns. In both cohorts,
      there were interactions between family income and the percentages of children
      breastfed at different ages. In the early months, breastfeeding was more
      prevalent in high-income families, but from nine months onwards it was more
      common among the poor. Low birthweight babies enjoyed shorter duration of
      breastfeeding. Despite the progress observed during the decade, duration of
      breastfeeding is still far short of international recommendations, justifying
      further campaigns prioritizing low birthweight babies and those from low-income
      families.

PMID- 10904369
TI  - [Infant malnutrition and obesity in two population-based birth cohort studies in
      southern Brazil: trends and differences]
AB  - Prevalence of anthropometric deficits and of obesity were studied in two
      population-based birth cohort studies in the city of Pelotas in Southern Brazil,
      in 1982 and 1993. All hospital delivered babies in each one-year period were
      identified, and samples of approximately 20% were visited at home at around 12
      months of age, totalling 1,449 children submitted to anthropometric examination
      in 1982 and 1,359 in 1993. Losses and refusals accounted for 20% of the children
      in 1982 and 7% in 1993. In this 11-year period, prevalence of weight/age deficits
      (below -2 standard deviations of the NCHS reference) fell from 5.4% to 3.8%,
      while that of weight/height dropped from 1.3% to 0.8%. Height/age deficits
      increased slightly, from 5.3% to 6.1%, while the proportion of obese children
      increased from 4.0% to 6.7%. The increase in weight at 12 months was due to a
      more rapid weight gain in the first year, since birthweights remained unchanged.
      About 10% of the children from the lowest income group had weight/age or
      height/age deficits, compared to 3% or less of those with a high family income.
      On the other hand, obesity showed a direct association with income, except for
      the wealthiest group, where the prevalence dropped, possibly due to concern among
      these families about the consequences of infant obesity.

PMID- 10904370
TI  - [Maternal and child care in two population-based cohorts from southern Brazil:
      trends and differences]
AB  - Two cohort studies of mothers and children (1982 and 1993) were used to document
      changes in health care utilization patterns. The cohorts included all hospital
      deliveries in the city of Pelotas, Southern Brazil, for the two years. Some 20%
      of the mothers and children were visited at home at a median interval of one year
      later. However, there was a reduction in the percentage of mothers seeking care
      after the fifth month of pregnancy. The mean number of prenatal consultations
      increased to 7.6. Prenatal care indicators were significantly worse for low
      income and high-gestational-risk women. In 1993, caesarean sections accounted for
      31% of deliveries. The proportions of deliveries assisted by medical doctors
      increased to 88%. Low-income and high-risk mothers were less likely to have a
      caesarean section or to be assisted by a medical doctor. Over half of the
      deliveries in the highest income group were caesareans. Vaccine coverage at 12
      months increased over the decade. Socioeconomic differentials were also observed.
      The mean number of medical consultations during the first year of life decreased
      to 10.5, mainly due to a drop in preventive care. Although most health care
      indicators improved over the course of the decade, health services are still
      biased towards those who least need them.

PMID- 10904372
TI  - [Developmental status at 12 months of age in a cohort of children in southern
      Brazil: differences according birthweight and family income]
AB  - This study evaluated all children born in 1993 in hospitals from Pelotas, Rio
      Grande do Sul, Brazil. Besides a perinatal study, a sample of 20% (1400 children)
      was followed through home visits during the first year. During these visits the
      nutritional status was assessed and a screening test for development (Denver II
      Test) was performed. Thirty-four per cent of the children assessed at 12 months
      failed this screening. Failure was associated with socioeconomic status, with low
      income children presenting twice the risk of those from more affluent families
      (p<0,001). Failure in the screening test was also associated with birthweight,
      and children weighing less than 2,500 g showed three times the risk of those with
      a birthweight equal to or greater than 2,500 g (p<0,001). In addition, children
      weighing less than 2000 g at birth were at three times the risk of failing the
      test as compared to those weighing between 2000g and 2499g. Results suggest that
      birthweight and family income are strongly related to the potential risk of
      developmental delays at the age of 12 months. It also points to the need for
      systematic developmental screening and early intervention programs in children at
      risk.

PMID- 10904375
TI  - ?

PMID- 10904376
TI  - [Epidemiology and assessment of health care services: new research trends]
AB  - This article begins by analyzing the difficulty that Clinical Medicine,
      Epidemiology, and Health Planning and Administration have in dealing with the
      dynamic, complex social dimensions characterizing the technological organization
      of the diagnostic and therapeutic process, necessary for the production of health
      services' knowledge about diseases, a difficulty which has become more evident
      with the increasingly frequent and varied assessments in health care. The latest
      tendencies in "health services research" are analyzed, along with a priorization
      of effectiveness and outcomes, seeking to respond to the identified problems
      through a redefinition of objects and methodologies.

PMID- 10904377
TI  - [Training human resources in epidemiology and health services evaluation]
AB  - The topics and bibliography pertaining to Epidemiology and Health Services
      Evaluation are discussed in the light of our experience with graduate courses at
      the Brazilian National School of Public Health (ENSP), Oswaldo Cruz Foundation
      (FIOCRUZ). The authors believe that the essential element of evaluation is the
      assessment of interventions, and that the evaluator's role is to analyze health
      care as a protective (or risk) factor among other health determinants.
      Epidemiology has been considered noteworthy due to its ability to integrate
      health services/programs evaluation as its research subject. In our courses on
      this subject, the main epidemiological study designs applied to health services
      research are presented in one section, followed by a discussion about accuracy
      and reliability of measures and classifications. A third section of the course
      comprises theoretical and practical assumptions of evaluation models, and the
      fourth section develops the notion of the quality of health care quality
      assessment (meta-evaluation). The pivotal issue in the organization of the course
      is the expansion of research from the academy to health services, implying
      acknowledgement of the mutual benefit this partnership can bring about.

PMID- 10904378
TI  - [Epidemiological standards for assessing quality: a proposal]
AB  - This paper proposes a strategy for defining indicators to assess the quality of
      the process of health care, based on the identification of the objectives of the
      care being delivered and on the verification of whether the technical guidelines
      for the procedures are being enforced. The article goes on to apply the proposed
      methodology to the process of health care during childbirth, based on a
      perspective of comprehensive care and adopting both an individual and collective
      risk approach. It uses a data bank of 4,558 Simplified Perinatal Clinical
      Histories (CLAP/PAHO/WHO) from 12 hospitals.The indicators selected were:
      V.D.R.L., Rh blood typing, antitetanus vaccination, rate of cesarean sections,
      reception of the baby by a pediatrician at birth, Apgar score, evaluation of the
      gestational age by physical exam, rooming-in, exclusive breastfeeding upon
      discharge, and referral for a puerperal consultation. Methods for classification
      of hospitals were the sum of their scores for each indicator, gold standard, and
      ranking. This methodology warranted identification of one hospital with excellent
      quality of care, five with good care, two with fair care, and four whose
      performances were completely unsatisfactory. Finally, some remarks on the
      assessment of quality of health care are made and future developments are
      proposed.

PMID- 10904379
TI  - [Evaluation of health care by means of infant death investigation]
AB  - All deaths of children under one year of age and residing in the Pau da Lima
      Health District, in the city of Salvador, Bahia, Brazil, during the year 1991
      were investigated through home visits and analysis of patient files. The study
      measured effectiveness of health services by verifying potentially avoidable
      deaths and the level of medical care these children received. More than half of
      the total of 47 deaths were related to causes considered amenable to prompt
      action by health services; 10 (21.3%) of the deaths occurred at home or in public
      (outside of health care facilities). Loss of information occurred in 36 (76.6%)
      of the mother's interviews, related to incomplete information on the death
      certificate and to changes of address. Analysis of patient files in the health
      clinics showed a 58.3% loss of information, indicating low-quality organization
      of hospital statistics; there was a prevalence of consultations classified as
      inadequate or barely adequate, due mainly to problems with physical examination
      and treatment. Despite this study's operational limitations, the results point to
      problems of access, effectiveness, and adequacy in the health care process.

PMID- 10904380
TI  - [Indicators and standards proposal for the evaluation of the quality of hospital
      care: the case for bronchial asthma]
AB  - The objectives of this article are to propose indicators for evaluation of the
      quality of hospital management of bronchial asthma patients, based on explicit
      criteria from literature reviews. The central problem identified in the
      literature review is the erroneous evaluation of severity of asthma crises,
      either by patients and their relatives, or by health professionals at all levels
      of care, causing serious consequences not only for the patient, but for society
      as a whole. Mortality figures indicate that from 1980 to 1990, an average of 2000
      deaths per year from asthma occurred in Brazil, of which 70% occurred in
      hospital. Asthma was the fourth cause of hospitalization (hospital admissions),
      in the state of Rio de Janeiro in 1993. Only 12% of the admissions that resulted
      in death made use of the ICU. The above information highlights the need for a
      thorough evaluation of hospital care of bronchial asthma in Brazil, including a
      review of all admissions resulting in death and reviews of a sample of all
      bronchial asthma admissions. Proposed criteria are for this evaluation include:
      severity of the crise, treatment prescribed, information given to the patient and
      their relatives, and follow-up appointments made after discharge from hospital.

PMID- 10904381
TI  - [Household surveys as an evaluation tool for health services: a case study from
      the Southeast region of the Greater Sao Paulo Metropolitan Area, 1989-1990]
AB  - The increasing importance of health evaluation has raised the need of
      incorporating epidemiological methodology to assess both technologies and health
      services. Evaluation of health services performance requires population data to
      identify the unmet demand and patterns of health services utilization. Such data
      can be obtained through household surveys. A household survey in the Greater Sao
      Paulo Metropolitan Area identified the pattern of health services utilization by
      the local population. This pattern, which reflects current organization of health
      services, pointed to a low coverage level by local services, including public
      clinics, different profiles for users of private and public services, and a large
      demand for health services outside the area, mainly for childbirth. The
      information obtained through these surveys produces a "base line" for health
      planning and further evaluation and is central to the assessment of existing
      services. The advantages of household surveys in health services evaluation
      should be analyzed in relation to the potential use of such data and study costs,
      thereby designing the best cost-benefit relationship for each specific situation.

PMID- 10904382
TI  - [Methodology for estimating standards for quality in health care: the case of
      acute myocardial infarction]
AB  - This study outlines the steps for estimating quality standards in health care to
      be used in quality improvement programs and funding mechanisms, focusing on the
      case of acute myocardial infarction (AMI). The methodology is based on existing
      scientific evidence related to technologies currently used for treatment of AMI
      in Brazil. Hospital lethality was estimated for selected sets of technologies
      corresponding to more or less complex units. Basic parameters used for estimating
      standards were efficacy (percentage reduction in death rates ratio) and the
      percentage corresponding to the referent (indications) associated with each
      technology. Standards were adjusted for age and time interval from onset to
      hospital admission. Estimated standard hospital lethality varied from 28%
      (traditional care wards) to 8.5% (relatively complex coronary care units).
      Limitations of the proposed methodology are discussed.

PMID- 10904383
TI  - Reliability of medical audit in quality assessment of medical care.
AB  - Medical audit of hospital records has been a major component of quality of care
      assessment, although physician judgment is known to have low reliability. We
      estimated interrater agreement of quality assessment in a sample of patients with
      cardiac conditions admitted to an American teaching hospital. Physician-reviewers
      used structured review methods designed to improve quality assessment based on
      judgment. Chance-corrected agreement for the items considered more relevant to
      process and outcome of care ranged from low to moderate (0.2 to 0.6), depending
      on the review item and the principal diagnoses and procedures the patients
      underwent. Results from several studies seem to converge on this point.
      Comparisons among different settings should be made with caution, given the
      sensitivity of agreement measurements to prevalence rates. Reliability of review
      methods in their current stage could be improved by combining the assessment of
      two or more reviewers, and by emphasizing outcome-oriented events.

PMID- 10904384
TI  - [Epidemiology and health services]
AB  - The growing application of epidemiological investigation to the health and
      medical field has consolidated its various uses in health care services.
      Brazilian legislation now provides back-up for four different types of
      applications, although their implementation is still precarious: analysis of the
      health situation, epidemiological surveillance, etiological studies, and
      evaluation of health care services, programs, and technologies. Proper deployment
      of such epidemiological applications on both the political/institutional and
      operational levels will provide relevant subsidies for health services in
      conducting their activities.

PMID- 10904385
TI  - [AIDS in Brazil: a changing epidemic].

PMID- 10904386
TI  - [The spread of the AIDS epidemic in Brazil from 1987 to 1996: a spatial
      analysis].
AB  - Mean AIDS incidence rates were calculated for three time periods, 1987-89, 1990
      92, and 1993-96, using reported adult AIDS cases by county. The analysis included
      the following variables: "population of counties for resident AIDS cases";
      "proportion of population residing in urban areas", and "concentration of
      poverty", stratifying by gender and exposure categories. The Southeast region has
      experienced the lowest increase, contrasting with the steep rise observed in the
      North and South between the second and third study periods. Comparing variations
      in incidence rates from 1990-92 and 1993-96 by region or population, the greatest
      increase was among women. In the larger cities, AIDS cases among "homo/bisexual
      men" predominate, although the proportion of cases among men who have sex with
      men has decreased as heterosexual cases have undergone a continuous increase.
      IDUs have been the core stratum in medium-sized counties. For the smallest
      counties, heterosexual transmission has been the basic element in local dynamics.
      Even though AIDS is still an urban phenomenon in Brazil, the epidemic is
      spreading to rural counties. Until recently it has mainly affecting relatively
      more affluent areas, but there is now an evident spread of the epidemic to poorer
      areas.

PMID- 10904387
TI  - [Temporal study in AIDS-associated disease in Brazil, 1980-1999].
AB  - Trends in annual incidence of reported AIDS-associated opportunistic infections
      (OI/100 adults > 12 years old) among AIDS cases were estimated at the national
      level in Brazil from 1980 through May 1999. The analysis included chi-square and
      linear regression modeling. The opportunistic infections included: candidiasis
      (CD), tuberculosis (TB), Pneumocystis carinii pneumonia (PCP), neurotoxoplasmosis
      (NT), Kaposi sarcoma (KS), cryptococcal meningitis (CM), and protozoa infections
      (PI). The overall cumulative incidence rates/100 reported AIDS cases were: CD =
      59, TB = 26, PCP = 23, NT = 15, KS = 5, CM = 4, and PI = 4. Annual trends
      indicated a statistically significant decline in all OIs. However, in the
      Northeast and Central-West regions there were increases in TB (b = 0.39) and NT
      (b = 0.20), respectively. TB showed a higher incidence among individuals with
      less schooling (< 8 years), while PCP and KS had higher incidence rates among
      those with 8 or more years of schooling, despite similar downward trends. Access
      to antiretroviral therapy and OI prophylaxis may partially explain these results.
      However, data reliability, delay in reporting, OI incidence after AIDS, and
      reporting and diagnostic criteria are factors that also need to be carefully
      assessed.

PMID- 10904388
TI  - [Dynamic models and social networks: a review and reflections on their
      contribution to understanding the HIV epidemic].
AB  - Due to certain specificities in the HIV epidemic, its spread has escaped the
      random transmission pattern of other infectious diseases. Observation of the
      epidemic has shown that individual behavior - relational patterns among
      individuals - plays a crucial role in HIV transmission and that strategies to
      prevent the epidemic's spread should take this factor into account in order to
      foster efficient allocation of existing resources. Mathematical and statistical
      models applying the behavioral approach to the epidemic have estimated
      interactions between groups whose characteristics and behaviors varied. However,
      such models have been more "post-dictive" than predictive, due to the inadequate
      representation of social structures in populations through which infectious
      agents spread. The social network methodology thus came to be applied to the
      approach to the HIV epidemic. This article discusses alternatives for the
      application of this methodology to the Brazilian epidemic, considering that
      sociometric risk networks structure the flow of infectious agents in communities,
      creating unique opportunities to interrupt their spread.

PMID- 10904389
TI  - [Classification by occupation of AIDS cases in Brazil - 1995].
AB  - Based on occupational classification of AIDS cases reported in Brazil in 1995 and
      recorded in the Data Base for Reported Diseases (SINAN), AIDS incidence rates
      were estimated per 100 thousand inhabitants by occupation, according to the 1991
      National Census. Nationwide rates for employed males and females were 25.0 and
      9.1, respectively. Among males, and within the major occupational groups, the
      following sub-groups had the highest rates: personal hygiene services (268.1),
      social scientists (176.1), writers and journalists (114.3), medical and dental
      assistants (113.4), chemists, pharmacists, and physicists (111.9), teachers
      (87.3), artists (74.7), port services (65.6), maritime and fluvial transportation
      (57.5), and sales personnel (55.4). The results indicated the disease's magnitude
      in different occupational categories and highlighted certain occupations in which
      special preventive measures are justified, along with more in-depth studies
      focusing on other socioeconomic variables and the sociocultural behavior of their
      members.

PMID- 10904390
TI  - [AIDS and pauperization: principal concepts and empirical evidence].
AB  - This paper discusses methodologies for analyzing relations between social
      inequalities, marginalization, prejudice, and vulnerability to HIV/AIDS,
      highlighting current difficulties and alternative research strategies. It also
      reviews the international and Brazilian literature, emphasizing: economic and
      macropolitical dimensions in the spread of HIV/AIDS; the role of drug policies
      and consumption; gender inequalities and prejudice; racial/ethnic inequalities
      and prejudice; and interaction with other STIs and their relationship to poverty;
      HIV/AIDS and health care standards, especially access to antiretroviral therapy;
      and human rights violations. Despite current methodological dilemmas in analyzing
      relations between psychosocial, cultural, and sociopolitical variables and
      vulnerability to HIV/AIDS and the limited Brazil literature, such themes merit
      further investigation, addressing Brazilian social and cultural specificities and
      profiting from recently developed research strategies.

PMID- 10904391
TI  - [AIDS and level of education in Brazil: temporal evolution from 1986 to 1996].
AB  - This article analyzes the temporal distribution of reported AIDS cases by level
      of education used as a proxy variable for individual socioeconomic status. All
      AIDS cases aged 20-69 years and reported through May 29, 1999, with date of
      diagnosis between 1986-1996, were included in the study. Incidence rates were
      calculated for men and women according to level of education ("level 1" up to 8
      years of schooling and "level 2" with over 8 years of schooling), by five
      geographic regions, and by year of diagnosis. Incidence rates for men with less
      schooling were close to or higher than those for men with more schooling
      (particularly in the Southeast region). For women, a time series showed that
      incidence rates increased at a higher rate among women with less schooling in all
      regions of the country; in the Southeast, the incidence rate for women with less
      schooling was already greater than for women with more schooling by 1989.
      According to the present analysis, the AIDS epidemic in Brazil began among people
      from the more highly educated social strata and progressed steadily through to
      the less educated social strata, especially among women.

PMID- 10904393
TI  - [Knowledge, attitudes, and practices of Brazilian women treated in the primary
      health care system concerning sexually transmitted diseases].
AB  - An increase has been observed in the prevalence of HIV infection among Brazilian
      women in recent years. This study focused on women's knowledge, attitudes, and
      practices towards prevention of sexually transmitted diseases (STDs) in the
      primary health care system in Campinas, Sao Paulo. Of the 249 women interviewed,
      10% reported condom use, while consistent use was reported by 7.6%. Although most
      women reported receiving information from television (87.6%), the quality of such
      information was insufficient to sensitize women as to their risk of exposure to
      STD. Most of the women reported physician confidence as an important factor. We
      conclude that women do not opt for condoms to prevent STD/AIDS, but as a
      contraceptive method. An instructive dialogue on STD/AIDS should be adopted
      during physician consultation, and the kind and quality of information should be
      updated to foster compliance with safer sex practices by the population.

PMID- 10904392
TI  - [Poverty and HIV/AIDS: anthropological and sociological aspects].
AB  - Focusing on the HIV/AIDS epidemic as a summation of several epidemics coexisting
      in the same space and drawing on Brazilian epidemiological data, we argue that
      the epidemic there shows variations already described elsewhere, such as
      feminization, pauperization, juvenization and interiorization, as a result of the
      deep inequalities characteristic of Brazilian society. We then examine the
      contributions of three bodies of sociological and anthropological literature
      related to HIV/AIDS: 1) sociological research and theory on the impact of recent
      global economic restructuring and social transformation, and its relationship to
      public health issues; 2) the cross-cultural and cross-national anthropological
      and sociological literature on structural factors shaping the course of the
      epidemic in different settings; and 3) the body of anthropological and
      sociological research on the synergistic effects of HIV/AIDS, social exclusion,
      and related social problems in pockets of extreme poverty in the large cities of
      core countries. We conclude that prevention policies for HIV/AIDS should deal
      comprehensively with diverse dimensions that determine differential
      vulnerabilities to the epidemic, thus requiring substantial social
      transformations.

PMID- 10904394
TI  - [Risk behavior among Brazilian Military conscripts, 1998: an study of HIV
      infections following socioeconomic differences].
AB  - A study of HIV-related risk behavior was carried out in 1998 among Brazilian
      military conscripts aged 17-20 years. A sample of 30,318 subjects was selected in
      three strata, pertaining to counties from: 1) the North and Central-West (N/CW);
      2) South (S); and the states of Rio de Janeiro and Sao Paulo. HIV prevalence
      rates were estimated in all strata. The objective of this paper was to analyze
      the results according to differences in socioeconomic status (SES). The
      statistical analysis used an index of sexual risk behavior and logistic
      regression models. The N/CW stratum showed the worst indicators for SES, sexual
      risk behavior, and sexually transmitted infections (STIs), as well as the highest
      HIV seroprevalence rate. The best indicators for all variables were found in the
      RJ/SP stratum. The South showed intermediate results. Level of schooling also
      played a relevant role. In all three strata the conscripts with an incomplete
      high school education displayed the worst sexual risk behavior index, shown to be
      a relevant predictor of STI-related problems, including HIV infection.

PMID- 10904395
TI  - [Estimated number of orphans due to maternal AIDS in Brazil, 1987-99].
AB  - This study proposes a procedure to estimate the number of orphans due to maternal
      AIDS. The procedure estimates the number of orphans by calendar year, multiplying
      the cumulative fertility rate by the number of AIDS deaths among women aged 15-49
      years. Because the procedure refers to the number of children that are alive, the
      estimate is adjusted by contemplating the proportion of pediatric AIDS cases due
      to vertical transmission and the probability of survival in the 5-9-year age
      group. To estimate the number of AIDS orphans in Brazil from 1987 to 1999, the
      procedure was applied by stratifying according to geographical region, taking
      into account the differences in regional fertility rates, completeness of death
      reporting, and misclassification of AIDS-related deaths as due to other causes.
      The total number of cumulative AIDS orphans for 1987-99 was estimated at
      approximately 30,000.

PMID- 10904396
TI  - [Estimated number of HIV-infected individuals aged 15-49 years in Brazil, 1998].
AB  - This study estimates the number of HIV-infected individuals from 15 to 49 years
      of age in Brazil in 1998 based on sentinel population studies in pregnant women,
      with a selection bias in the sample. A principal components procedure was used to
      group 44 counties in homogeneous 13 clusters. Two indicators were constructed for
      each cluster: a) the logarithm of the accumulated AIDS incidence rate among women
      from 15 to 34 years of age (1996) and b) the logarithm of the growth ratio for
      the mean AIDS incidence rate for women from 15 to 34 years of age for the period
      from 1990-1992 to 1993-1996. Taking the log of the proportion of HIV-infected
      pregnant women as the dependent variable and the two above-mentioned indicators
      as the independent variables, a regression line was fitted to the aggregate data.
      Estimation of the model's parameters allowed us to calculate the proportion of
      infected individuals by macro-region, by age (15-34 and 35-49 years) and gender.
      The point estimate was 536 thousand HIV-infected adults with a 68% CI (470.689 -
      603.305).

PMID- 10904397
TI  - Risk factors for tuberculosis among human immunodeficiency virus-infected
      persons. A case-control study in Belo Horizonte, Minas Gerais, Brazil (1985
      1996).
AB  - The objective of this study was to identify tuberculosis risk factors and
      possible surrogate markers among human immunodeficiency virus (HIV)-infected
      persons. A retrospective case-control study was carried out at the HIV outpatient
      clinic of the Universidade Federal de Minas Gerais in Belo Horizonte. We reviewed
      the demographic, social-economical and medical data of 477 HIV-infected
      individuals evaluated from 1985 to 1996. The variables were submitted to an
      univariate and stratified analysis. Aids related complex (ARC), past history of
      pneumonia, past history of hospitalization, CD4 count and no antiretroviral use
      were identified as possible effect modifiers and confounding variables, and were
      submitted to logistic regression analysis by the stepwise method. ARC had an odds
      ratio (OR) of 3.5 (CI 95% - 1.2-10.8) for tuberculosis development. Past history
      of pneumonia (OR 1.7 - CI 95% 0.6-5.2) and the CD4 count (OR 0.4 - CI 0. 2-1.2)
      had no statistical significance. These results show that ARC is an important
      clinical surrogate for tuberculosis in HIV-infected patients. Despite the need of
      confirmation in future studies, these results suggest that the ideal moment for
      tuberculosis chemoprophylaxis could be previous to the introduction of
      antiretroviral treatment or even just after the diagnosis of HIV infection.

PMID- 10904398
TI  - Trypanosoma cruzi infection in Leontopithecus rosalia at the Reserva Biologica de
      Poco das Antas, Rio de Janeiro, Brazil.
AB  - Wild golden lion tamarins (Leontopithecus rosalia) - endangered primates that are
      native to the Brazilian Atlantic coastal forest - were surveyed for the presence
      of Trypanosoma cruzi with the use of Giemsa-stained blood smears, hemocultures
      and an indirect immunofluorescence assay (IFAT). Positive IFAT with titers
      ranging from 1:20 to 1:1280 were observed in 52% of the 118 wild tamarins
      examined and the parasite was isolated from 38 tamarins. No patent parasitemia
      was observed among the tamarins from which T. cruzi was isolated. Serum
      conversion and positive hemoculture was observed for three animals that had
      yielded negative results some months earlier, which indicates that T. cruzi is
      actively transmitted among tamarins. In contrast to observations with other
      sylvatic isolates, those from the tamarins were significantly more virulent and
      most of them produced mortality in experimentally infected Swiss mice. Some
      variation in the kDNA restriction profiles among the isolates was observed.
      Electrophoresis with GPI, G6PDH, IDH, MDH and ME enzymes showed a Z2 profile.

PMID- 10904399
TI  - A review of the ticks (Acari, ixodida) of Brazil, their hosts and geographic
      distribution - 1. The state of Rio Grande do Sul, southern Brazil.
AB  - A review of the ticks (Acari, Ixodida) of the State of Rio Grande do Sul,
      southern Brazil, was completed as a step towards a definitive list (currently
      indicated as 12) of such species, their hosts and distribution. The ticks: Argas
      miniatus (poultry), Ixodes loricatus (opossums), Amblyomma aureolatum (dogs), A.
      calcaratum (anteaters), A. cooperi (capybaras), A. nodosum (anteaters), A.
      tigrinum (dogs) (Neotropical) and Rhipicephalus sanguineus (dogs) (introduced,
      cosmopolitan, Afrotropical) were confirmed as present, in addition to the
      predominant, Boophilus microplus (cattle) (introduced, pan-tropical, Oriental).
      Of the further 18 species thus far reported in the literature as present in the
      state, but unavailable for examination: only Ornithodoros brasiliensis (humans
      and their habitations) (Neotropical), Ixodes affinis (deer)
      (Nearctic/Neotropical) and I. auritulus (birds)
      (Nearctic/Neotropical/Afrotropical/ Australasian) are considered likely; 13
      species would benefit from corroborative local data but the majority appear
      unlikely; reports of A. maculatum (Nearctic/Neotropical, but circum-Caribbean)
      are considered erroneous; the validity of A. fuscum is in doubt. The very recent,
      first known report of the tropical Anocentor nitens
      (horses)(Nearctic/Neotropical), but still apparent absence of the tropical A.
      cajennense (catholic) (Nearctic/Neotropical) and the sub-tropical/temperate
      Ixodes pararicinus (cattle) (Neotropical) in Rio Grande do Sul are important for
      considerations on their current biogeographical distribution and its dynamics in
      South America. The state has relatively long established, introduced ("exotic"),
      Old World tick species (B. microplus, R. sanguineus) that continue to represent
      significant pests and disease vectors to their traditional, introduced domestic
      animal hosts, cattle and urban dogs. There are also indigenous, New World ticks
      (A. miniatus, O. brasiliensis, A. aureolatum, A. nitens), as both long
      established and possibly newly locally introduced species in the state, that
      should be considered as potential and emergent pests and pathogen vectors to
      humans and their more recently acquired, introduced domestic animal hosts; rural
      poultry, dogs and horses.

PMID- 10904400
TI  - Sexing sand fly pupae (Diptera: psychodidade: phlebotominae).
AB  - We describe a technique to separate male and female pupae of sand flies. This has
      reduced the labour to separate flies after emergence and also allows the
      isolation of unmated adults for behavioural and physiological studies.

PMID- 10904401
TI  - Mexican Trypanosoma cruzi stocks: analysis of minicircle kDNA homologies by cross
      hybridization.
AB  - Homologies of minicircle kDNA of 27 Mexican stocks were studied by cross
      hybridization with four kDNA probes derived from three reference stocks belonging
      to groups Trypanosoma cruzi I (SO34 cl4 and Silvio) and T. cruzi II (MN) and one
      Mexican stock. High homologies were only observed with Silvio (six stocks) and
      Mexican probes (11 stocks). After 30 min exposure (low homology) additional
      stocks were recognized with SO34 cl4 (three stocks) and Silvio (six stocks)
      probes; with the Mexican probe only five stocks remained non-reactive. All the
      stocks were typed by isoenzyme (16 loci) and Mexican stocks belonged to T. cruzi
      I. Hybridization patterns were not strictly correlated with the observed
      clustering and cross-hybridization of kDNA minicircles is not available to
      distinct Mexican stocks.

PMID- 10904402
TI  - Action of pentoxifylline on experimental cutaneous leishmaniasis due to
      Leishmania (Leishmania) amazonensis.
AB  - In the animal model of leishmaniasis caused by Leishmania (Leishmania)
      amazonensis there is a complex mechanism of the host-parasite interaction. The
      present study was performed to interfere with the inflammatory reaction to the
      parasites, through immune modulation. Female C5BL/6 isogenic mice were used, some
      of which were inoculated on the right ear and others on the right footpad with
      3.10(6) stationary phase promastigotes of the MHOM/BR/PH8 strain of L. (L.)
      amazonensis, and were allocated in three groups: the first received
      pentoxifylline 8mg/kg every 12 h, since the first day; the second one received
      the same dose since the 40th day of infection and a control group that did not
      receive any treatment. All the ears excised were analyzed to determine the
      variation in weight between both ears and for histopathological analyses. A
      quantification of the parasites was done using the limiting dilution assay. A
      significant reduction of the number of parasites, was observed among the animals
      treated which had an accordingly significant reduction on the weight of the ears.
      Pentoxifylline reduced the macrophages propensity to vacuolation and induced a
      more effective destruction of the parasites by these cells. Moreover, the group
      that began the treatment later did not show the same effectiveness.

PMID- 10904404
TI  - Flow cytometry as a tool to identify Mycobacterium tuberculosis interaction with
      the immune system and drug susceptibility.
AB  - Flow cytometric analysis is a useful and widely employed tool to identify
      immunological alterations caused by different microorganisms, including
      Mycobacterium tuberculosis. However, this tool can be used for several others
      analysis. We will discuss some applications for flow cytometry to the study of M.
      tuberculosis, mainly on cell surface antigens, mycobacterial secreted proteins,
      their interaction with the immune system using inflammatory cells recovered from
      peripheral blood, alveolar and pleura spaces and the influence of M. tuberculosis
      on apoptosis, and finally the rapid determination of drug susceptibility. All of
      these examples highlight the usefulness of flow cytometry in the study of M.
      tuberculosis infection.

PMID- 10904403
TI  - Comparison of dengue infection in human mononuclear leukocytes with mosquito
      C6/36 and mammalian Vero cells using flow cytometry to detect virus antigen.
AB  - Fluorescent activated cell sorter (FACS) analysis is useful for the detection of
      cellular surface antigens and intracellular proteins. We used this methodology in
      order to detect and quantify dengue antigens in highly susceptible cells such as
      clone C6/36 (Aedes albopictus) and Vero cells (green monkey kidney).
      Additionally, we analyzed the infection in vitro of human peripheral blood
      mononuclear leukocytes (PBML). FACS analysis turned out to be a reliable
      technique to quantify virus growth in traditional cell cultures of C6/36 as well
      as Vero cells. High rates of infection were achieved with a good statistical
      correlation between the virus amount used in infection and the percentage of
      dengue antigen containing cells detected in infected cultures. We also showed
      that human monocytes (CD14+) are preferred target cells for in vitro dengue
      infection among PBML. Monocytes were much less susceptible to virus infection
      than cell lines but they displayed dengue antigens detected by FACS five days
      after infection. In contrast, lymphocytes showed no differences in their profile
      for dengue specific immunofluorescence. Without an animal model to reproduce
      dengue disease, alternative assays have been sought to correlate viral virulence
      with clinical manifestations and disease severity. Study of in vitro interaction
      of virus and host cells may highlight this relationship.

PMID- 10904406
TI  - Amino acid sequences of proteins from Leptospira serovar pomona.
AB  - This report describes a partial amino acid sequences from three putative outer
      envelope proteins from Leptospira serovar pomona. In order to obtain internal
      fragments for protein sequencing, enzymatic and chemical digestion was performed.
      The enzyme clostripain was used to digest the proteins 32 and 45 kDa. In situ
      digestion of 40 kDa molecular weight protein was accomplished using cyanogen
      bromide. The 32 kDa protein generated two fragments, one of 21 kDa and another of
      10 kDa that yielded five residues. A fragment of 24 kDa that yielded nineteen
      residues of amino acids was obtained from 45 kDa protein. A fragment with a
      molecular weight of 20 kDa, yielding a twenty amino acids sequence from the 40
      kDa protein.

PMID- 10904405
TI  - A GBP 130 derived peptide from Plasmodium falciparum binds to human erythrocytes
      and inhibits merozoite invasion in vitro.
AB  - The malarial GBP 130 protein binds weakly to intact human erythrocytes; the
      binding sites seem to be located in the repeat region and this region's
      antibodies block the merozoite invasion. A peptide from this region (residues
      from 701 to 720) which binds to human erythrocytes was identified. This peptide
      named 2220 did not bind to sialic acid; the binding site on human erythrocyte was
      affected by treatment with trypsin but not by chymotrypsin. The peptide was able
      to inhibit Plasmodium falciparum merozoite invasion of erythrocytes. The residues
      F701, K703, L705, T706, E713 (FYKILTNTDPNDEVERDNAD) were found to be critical for
      peptide binding to erythrocytes.

PMID- 10904407
TI  - The trypanosomatid evolution workshop London School of Hygiene and Tropical
      Medicine. 17-18 February 2000.
AB  - The trypanosome evolution workshop, a joint meeting of the University of Exeter
      and the London School of Hygiene and Tropical Medicine, focused on topics
      relating to trypanosomatid and vector evolution. The meeting, sponsored by The
      Wellcome Trust, The Special Programme for Research and Training in Tropical
      Disease of World Health Organization and the British Section of the Society of
      Protozoologists, brought together an international group of experts who presented
      papers on a wide range of topics including parasite and vector phylogenies,
      molecular methodology and relevant biogeographical data.

PMID- 10904408
TI  - Plate tectonics, seaways and climate in the historical biogeography of mammals.
AB  - The marsupial and placental mammals originated at a time when the pattern of
      geographical barriers (oceans, shallow seas and mountains) was very different
      from that of today, and climates were warmer. The sequence of changes in these
      barriers, and their effects on the dispersal of the mammal families and on the
      faunas of mammals in the different continents, are reviewed. The mammal fauna of
      South America changed greatly in the Pliocene/Pleistocene, when the newly
      complete Panama Isthmus allowed the North American fauna to enter the continent
      and replace most of the former South American mammal families. Marsupial, but not
      placental, mammals reached Australia via Antarctica before Australia became
      isolated, while rats and bats are the only placentals that dispersed naturally
      from Asia to Australia in the late Cenozoic. Little is known of the early history
      of the mammal fauna of India. A few mammal families reached Madagascar from
      Africa in the early Cenozoic over a chain of islands. Africa was isolated for
      much of the early Cenozoic, though some groups did succeed in entering from
      Europe. Before the climate cooled in the mid-Cenozoic, the mammal faunas of the
      Northern Hemisphere were much richer than those of today.

PMID- 10904409
TI  - Insect trypanosomatids: the need to know more.
AB  - Of ten recognized trypanosomatid genera, only two - pathogenic Trypanosoma and
      Leishmania - have been actively investigated for any length of time while the
      plant flagellates - Phytomonas - have recently begun to attract attention due to
      their role as agricultural parasites. The remaining genera that comprise
      parasites associated with insects have been largely neglected except for two or
      three containing popular isolates. This publication reviews current knowledge of
      trypanosomatids from insects.

PMID- 10904410
TI  - Future trypanosomatid phylogenies: refined homologies, supertrees and networks.
AB  - There has been good progress in inferring the evolutionary relationships within
      trypanosomes from DNA data as until relatively recently, many relationships have
      remained rather speculative. Ongoing molecular studies have provided data that
      have adequately shown Trypanosoma to be monophyletic and, rather surprisingly,
      that there are sharply contrasting levels of genetic variation within and between
      the major trypanosomatid groups. There are still, however, areas of research that
      could benefit from further development and resolution that broadly fall upon
      three questions. Are the current statements of evolutionary homology within
      ribosomal small sub-unit genes in need of refinement? Can the published
      phylograms be expanded upon to form 'supertrees' depicting further relationships?
      Does a bifurcating tree structure impose an untenable dogma upon trypanosomatid
      phylogeny where hybridisation or reticulate evolutionary steps have played a
      part? This article briefly addresses these three questions and, in so doing,
      hopes to stimulate further interest in the molecular evolution of the group.

PMID- 10904412
TI  - Trypanosoma cruzi - the vector-parasite paradox.
AB  - Trypanosoma cruzi and the majority of its insect vectors (Hemiptera, Reduviidae,
      Triatominae) are confined to the Americas. But while recent molecular studies
      indicate a relatively ancient origin for the parasite ( approximately 65 million
      years ago) there is increasing evidence that the blood-sucking triatomine vectors
      have evolved comparatively recently (<5 mya). This review examines the evidence
      for these ideas, and attempts to reconcile the apparent paradox by suggesting
      that marsupial opossums (Didelphidae) may have played a role, not just as
      original reservoir hosts, but also as original vectors of the parasite.

PMID- 10904411
TI  - Genomic rearrangements in trypanosomatids: an alternative to the "one gene"
      evolutionary hypotheses?
AB  - Most molecular trees of trypanosomatids are based on point mutations within DNA
      sequences. In contrast, there are very few evolutionary studies considering DNA
      (re) arrangement as genetic characters. Waiting for the completion of the various
      parasite genome projects, first information may already be obtained from
      chromosome size-polymorphism, using the appropriate algorithms for data
      processing. Three illustrative models are presented here. First, the case of
      Leishmania (Viannia) braziliensis/L. (V.) peruviana is described. Thanks to a
      fast evolution rate (due essentially to amplification/deletion of tandemly
      repeated genes), molecular karyotyping seems particularly appropriate for
      studying recent evolutionary divergence, including eco-geographical
      diversification. Secondly, karyotype evolution is considered at the level of
      whole genus Leishmania. Despite the fast chromosome evolution rate, there is
      qualitative congruence with MLEE- and RAPD-based evolutionary hypotheses.
      Significant differences may be observed between major lineages, likely
      corresponding to major and less frequent rearrangements (fusion/fission,
      translocation). Thirdly, comparison is made with Trypanosoma cruzi. Again
      congruence is observed with other hypotheses and major lineages are delineated by
      significant chromosome rearrangements. The level of karyotype polymorphism within
      that "species" is similar to the one observed in "genus" Leishmania. The
      relativity of the species concept among these two groups of parasites is
      discussed.

PMID- 10904413
TI  - Analysis of genetic diversity of Trypanosoma cruzi: an application of
      riboprinting and gradient gel electrophoresis methods.
AB  - Analysis of restriction fragment length polymorphism (RFLP) profiles derived from
      digestion of polymerase chain reaction (PCR) products of the ribosomal 18S from
      Trypanosoma cruzi yields a typical 'riboprint' profile that can vary
      intraspecifically. A selection of 21 stocks of T. cruzi and three outgroup taxa:
      T. rangeli, T. conorhini and Leishmania braziliensis were analysed by
      riboprinting to assess divergence within and between taxa. T. rangeli, T.
      conorhini and L. braziliensis could be easily differentiated from each other and
      from T. cruzi. Phenetic analysis of PCR-RFLP profiles indicated that, with one or
      two exceptions, stocks of T. cruzi could be broadly partitioned into two groups
      that formally corresponded to T. cruzi I and T. cruzi II respectively. To test if
      ribosomal 18S sequences were homogeneous within each taxon, gradient gel
      electrophoresis methods were employed utilising either chemical or temperature
      gradients. Upon interpretation of the melting profiles of riboprints and a
      section of the 18S independently amplified by PCR, there would appear to be at
      least two divergent 18S types present within T. cruzi. Heterogeneity within
      copies of the ribosomal 18S within a single genome has therefore been
      demonstrated and interestingly, this dimorphic arrangement was also present in
      the outgroup taxa. Presumably the ancestral duplicative event that led to the
      divergent 18S types preceded that of speciation within this group. These
      divergent 18S paralogues may have, or had, different functional pressures or
      rates of molecular evolution. Whether or not these divergent types are equally
      transcriptionally active throughout the life cycle, remain to be assessed.

PMID- 10904414
TI  - Chagas disease and human migration.
AB  - Human Chagas disease is a purely accidental occurrence. As humans came into
      contact with the natural foci of infection might then have become infected as a
      single addition to the already extensive host range of Trypanosoma cruzi that
      includes other primates. Thus began a process of adaptation and domiciliation to
      human habitations through which the vectors had direct access to abundant food as
      well as protection from climatic changes and predators. Our work deals with the
      extraction and specific amplification by polymerase chain reaction of T. cruzi
      DNA obtained from mummified human tissues and the positive diagnosis of Chagas
      disease in a series of 4, 000-year-old Pre-Hispanic human mummies from the
      northern coast of Chile. The area has been inhabited at least for 7,000 years,
      first by hunters, fishers and gatherers, and then gradually by more permanent
      settlements. The studied specimens belonged to the Chinchorro culture, a people
      inhabiting the area now occupied by the modern city of Arica. These were
      essentially fishers with a complex religious ideology, which accounts for the
      preservation of their dead in the way of mummified bodies, further enhanced by
      the extremely dry conditions of the desert. Chinchorro mummies are, perhaps, the
      oldest preserved bodies known to date.

PMID- 10904415
TI  - The ecotopes and evolution of triatomine bugs (triatominae) and their associated
      trypanosomes.
AB  - Triatomine bug species such as Microtriatoma trinidadensis, Eratyrus mucronatus,
      Belminus herreri, Panstrongylus lignarius, and Triatoma tibiamaculata are
      exquisitely adapted to specialist niches. This suggests a long evolutionary
      history, as well as the recent dramatic spread a few eclectic, domiciliated
      triatomine species. Virtually all species of the genus Rhodnius are primarily
      associated with palms. The genus Panstrongylus is predominantly associated with
      burrows and tree cavities and the genus Triatoma with terrestrial rocky habitats
      or rodent burrows. Two major sub-divisions have been defined within the species
      Trypanosoma cruzi, as T. cruzi 1 (Z1) and T. cruzi 2 (Z2). The affinities of a
      third group (Z3) are uncertain. Host and habitat associations lead us to propose
      that T. cruzi 1 (Z1) has evolved in an arboreal, palm tree habitat with the
      triatomine tribe Rhodniini, in association with the opossum Didelphis. Similarly
      we propose that T. cruzi (Z2) and Z3 evolved in a terrestrial habitat in burrows
      and in rocky locations with the triatomine tribe Triatomini, in association with
      edentates, and/or possibly ground dwelling marsupials. Both sub-divisions of T.
      cruzi may have been contemporary in South America up to 65 million years ago.
      Alternatively, T. cruzi 2 (Z2) may have evolved more recently from T. cruzi 1
      (Z1) by host transfers into rodents, edentates, and primates. We have constructed
      a molecular phylogeny of haematophagous vectors, including triatomine bugs, which
      suggests that faecal transmission of trypanosomes may be the ancestral route. A
      molecular clock phylogeny suggests that Rhodnius and Triatoma diverged before the
      arrival, about 40 million years ago, of bats and rodents into South America.

PMID- 10904416
TI  - Nuclear rDNA-based molecular clock of the evolution of triatominae (Hemiptera:
      reduviidae), vectors of Chagas disease.
AB  - The evolutionary history and times of divergence of triatomine bug lineages are
      estimated from molecular clocks inferred from nucleotide sequences of the small
      subunit SSU (18S) and the second internal transcribed spacer (ITS-2) of the
      nuclear ribosomal DNA of these reduviids. The 18S rDNA molecular clock rate in
      Triatominae, and Prosorrhynchan Hemiptera in general, appears to be of 1.8% per
      100 million years (my). The ITS-2 molecular clock rate in Triatominae is
      estimated to be around 0.4-1% per 1 my, indicating that ITS-2 evolves 23-55 times
      faster than 18S rDNA. Inferred chronological data about the evolution of
      Triatominae fit well with current hypotheses on their evolutionary histories, but
      suggest reconsideration of the current taxonomy of North American species
      complexes.

PMID- 10904418
TI  - Further support for a Palaearctic origin of Leishmania.
AB  - The fossil record and systematics of murid rodents, reservoirs of zoonotic
      cutaneous leishmaniasis in the Palaearctic, Oriental, African, Nearctic and
      Neotropical, strongly support a Palaearctic origin of Leishmania. The fossil
      record and systematics of phlebotomine sand flies reinforce this idea.
      Interpretations of molecular data that place the origin of Leishmania in the
      Neotropical are inconsistent with the natural histories of reservoirs and
      vectors. The evolutionary pattern of New World rats (Sigmodontinae) indicates
      that they may be the most important reservoirs of zoonotic cutaneous
      leishmaniasis throughout their range.

PMID- 10904417
TI  - Evidence for a neotropical origin of Leishmania.
AB  - Contradictory biogeographic hypotheses for either a Neotropical or a Palaearctic
      origin of the genus Leishmania have been proposed. Hypotheses constructed on the
      basis of biogeographic data must be tested against an independent dataset and
      cannot be supported by biogeographic data alone. In the absence of a fossil
      record for the Leishmania these two hypotheses were tested against a combined
      dataset of sequences from the DNA polymerase A catalytic subunit and the RNA
      polymerase II largest subunit. The phylogeny obtained provided considerable
      support for a Neotropical origin of the genus Leishmania and leads us to reject
      the hypothesis for a Palaearctic origin.

PMID- 10904419
TI  - Speculations on the origin and evolution of the genus Leishmania.
AB  - Recently two hypotheses have been proposed for the evolution of Leishmania
      involving respectively a Neotropical or Paleartic origin for the species. Here an
      alternative proposal on the phylogeny of Leishmania based on the major divisions
      within the genus is presented. In this hypothesis a Neotropic origin is retained
      for L. (Viannia) and Paraleishmania, a recently described section within the
      genus Leishmania, while an African origin is proposed for L. (Leishmania) and
      possibly Sauroleishmania. The current distribution of Leishmania in the
      Neotropics is explained as the product of multiple introductions of Leishmania
      parasites into the New World. Problems with organismal identity in
      Sauroleishmania and the use of molecular sequence data in inferring phylogenies
      are also discussed.

PMID- 10904420
TI  - Sand fly evolution and its relationship to Leishmania transmission.
AB  - The evolutionary relationships of sand flies and Leishmania are discussed in this
      report, which draws distinctions between co-association, co-evolution and co
      speciation (or co-cladogenesis). Examples focus on Phlebotomus vectors of Le.
      infantum and Le. major in the Mediterranean subregion.

PMID- 10904422
TI  - Link between Helicobacter pylori infection and idiopathic parkinsonism.
AB  - The conventional concept for an environmental cause of idiopathic parkinsonism is
      an insult (e.g. neurotoxin or encephalitis), superimposed on age-related
      attrition of nigral dopaminergic neurons, and temporally remote from neurological
      diagnosis. To the contrary, we describe the fit of Helicobacter pylori. This
      commonest of known bacterial infections, usually acquired in childhood, persists,
      and has been linked with peptic ulcer/non-ulcer dyspepsia, immunosuppression and
      autoimmunity. Acquired immunosuppression, predisposing to auto-immunity, is
      assessed as a model for the pathogenesis of parkinsonism and parkinsonian-like
      attributes of ageing. Eradication of a trigger has potential to change the
      approach to parkinsonism, just as it did to peptic ulcer. The tenet of inevitable
      age-related attrition of dopaminergic neurons may also require revision.

PMID- 10904421
TI  - Acidic ribosomal proteins and histone H3 from Leishmania present a high rate of
      divergence.
AB  - Another additional peculiarity in Leishmania will be discussed about of the amino
      acid divergence rate of three structural proteins: acidic ribosomal P1 and P2b
      proteins, and histone H3 by using multiple sequence alignment and dendrograms.
      These structural proteins present a high rate of divergence regarding to their
      homologous protein in Trypanosoma cruzi. At this regard, L. (V.) peruviana P1 and
      T. cruzi P1 showed 57.4% of divergence rate. Likewise, L. (V.) braziliensis
      histone H3 and acidic ribosomal P2 protein exhibited 31.8% and 41.7% respectively
      of rate of divergence in comparison with their homologous in T. cruzi.

PMID- 10904423
TI  - Expression of one group of genes maintains one unit of long-term memory in a
      brain model.
AB  - In a brain model, a unit of long-term memory is stored in the encoding synapses
      of a neuron as a presynaptic axonal 'on-off' pattern through the establishment of
      long-term potentiation (LTP) and long-term depression (LTD). Repetitive
      activation of one presynaptic axonal 'on-off' pattern speeds up the subsequent re
      activation of the same pattern by inducing expression of a corresponding group of
      genes in support of the enzymes, protein substrates, and second messengers for
      the LTP and LTD that encode the unit of long-term memory. Phantom limb pains are
      memorized and re-activated through the expression of the corresponding group of
      genes, and re-experiencing the stressful event in post traumatic stress syndrome
      results from the expression of another group of genes. The sense of requiring
      less time to experience the content of a successfully retrieved long-term memory
      reflects an increased speed of re-activating the presynaptic axonal 'on-off'
      patterns of the memory, or an increased speed of thinking. Giving rise to a sense
      of familiarity with new things, deja vu may also be a mental state with increased
      speed of thinking. The speed of thinking may be decreased in jamais vu that is
      opposite to deja vu. Progressive increases in the speed of thinking when engaging
      in a hobby may open up a previously unused neural pathway that turns a previously
      happy feeling into an aversive one.

PMID- 10904425
TI  - How infections with non-retroviral RNA viruses may be involved in the development
      of neoplasia.
AB  - There have been reports of associations of infections with non-retroviral RNA
      viruses and tumour development. A hypothesis is proposed as to how non-retroviral
      RNA viruses may play a role in the development of neoplasia. It is based on a
      recent report of the detection of complementary DNA (cDNA) of the RNA virus
      lymphocytic choriomeningitis virus in mouse and hamster cells. This lends
      credence to the claim made in 1975 of the detection of cDNA copies of genomic DNA
      of three non-retroviral RNA viruses integrated into the DNA of host cells.
      Briefly, the hypothesis proposes that at least one cDNA fragment of a non
      retroviral RNA virus is synthesized and integrated into the genome of the host
      cell in a way that could lead or contribute to tumour development. General
      approaches for testing the hypothesis are outlined.

PMID- 10904424
TI  - Is cancer an autoimmune process dependent on anti-apoptotic autoantibodies?
AB  - Dysregulated apoptosis is a potentially important mechanism in the pathogenesis
      of cancer. Autoantibodies, which inhibit apoptosis, have recently been identified
      in patients with malignant diseases. We suggest that such inhibitory
      autoantibodies participate in tumorigenesis. These views may provide a basis for
      the increased incidence of cancer in patients with autoimmune diseases and have
      novel therapeutic implications for cancer.

PMID- 10904426
TI  - Uterine haemodynamics as a possible driving force for endovascular trophoblast
      migration in the placental bed.
AB  - Uteroplacental vascular adaptation during pregnancy depends on retrograde
      endovascular migration of trophoblast in the uterine spiral arteries and their
      subsequent incorporation into the vessel wall. In the human, this migration
      process occurs in a step-wise fashion, starting with plugging of the distal ends
      of the arteries, followed by migration into the decidual and, after several
      weeks' delay, into the myometrial segments. The hypothesis is put forward that
      haemodynamical forces play an important regulatory role in this process. A
      mechanical signal transduction system should then be present within the
      trophoblastic cells to trigger their rheotactic behaviour. Since the condition of
      preeclampsia is characterized by restricted colonization of spiral arteries by
      trophoblast, the implications of this proposed regulatory system on the
      pathogenesis of the disease are considered.

PMID- 10904427
TI  - Is Helicobacter pylori a cause of infantile hypertrophic pyloric stenosis?
AB  - My hypothesis is that infantile hypertrophic pyloric stenosis (IHPS) is caused in
      some cases by Helicobacter pylori (HP) a bacterium commonly found in the human
      stomach. IHPS is an idiopathic condition of infancy. It occurs at about 5 weeks
      of age in 3 per 1000 newborns. Children with IHPS have structurally normal pylori
      at birth and do not resemble children with congenital anomalies. Some nonspecific
      evidence (temporal distribution, seasonality, familial clustering, leukocytic
      infiltrates, and increased risk with bottle feeding) are compatible with an
      infectious etiology. Some other epidemiologic features of IHPS, such as its
      strong male predominance, its racial and social class variation, and a possible
      drop in its incidence, are also features of HP infection. Clinical features of
      IHPS, such as vomiting, hematemesis, and esophagitis, are also consistent with
      HP. Finally, children with IHPS appear to be more likely to develop chronic
      conditions, such as peptic ulcers, now known to be caused by HP.

PMID- 10904428
TI  - Homeostatic biophasal conscious regulation.
AB  - A new theory on consciousness is presented. According to our neuroscientific
      model, focal awareness is the result of neurophysiological patterns of voluntary
      or involuntary information, registration, storage and retrieval performed in
      accordance with organismic biphasal homeostatic rules and regulations that follow
      the demand-supply principle. The information-processing operation consists of
      three major elements: 1. Involuntary activated 'inherited schematic
      representation' (ISR) programs that monitor homeostatic negative feedback
      programs and remain inert during the storage period; 2. Voluntary activated
      'acquired engram linkage' (AEL) programs that monitor the preferential self
      efforts designed to maintain homeostasis and dynamic adaptational survival; this
      information remains fixed in the storage reservoir; and 3. Outer, nonselective
      sources of activation that derive from the assembly of the sensory information
      system. Consciousness is limited by the microneurostructural boundaries of
      'conscious instrument panel' (CIP) needed to handle this unique biological
      experience. At any unit of time, the conscious subjectively identifies states of
      pleasure (first phase of homeostasis maintenance) or displeasure (second phase of
      homeostasis) which are associated with the alarm subsystem of the 'organismic
      defense system' (ODS).Thus, consciousness is a form of neurophysiological
      activity that excludes unconscious existence in order to monitor information.
      This model promotes our understanding of the biological essences of
      consciousness.

PMID- 10904429
TI  - The wired network as a learning paradigm for normal and abnormal brain neuronal
      communication.
AB  - The brain is a highly sophisticated assembly of neuronal networks for interaction
      with the internal and external environment. Fundamentally, the neuronal
      communication process is analogous structurally and functionally to the
      electrical (wire-mediated) network. In particular, both have coupled information
      processing and conduction properties. We suggest that the electrical system can
      be used as a learning paradigm in brain research and clinical practice. Our model
      shows how the study of wire-mediated networks may be of benefit in tracing overt
      psychiatric manifestations to intrinsic biological faults in brain circuitry.

PMID- 10904430
TI  - Immune reaction links disease progression in cancer patients with depression.
AB  - Mood disturbances and depression are supposed to have a negative impact on
      patients' outcome in malignant tumour disease. On the other hand, poor prognosis
      in cancer patients is associated with chronic immune challenge which is
      paralleled by enhanced degradation of the essential amino acid tryptophan and
      thus decreased plasma tryptophan concentrations. Because tryptophan is precursor
      for the biosynthesis of the neurotransmitter serotonin (= 5-hydroxytryptamine,
      5HT), low tryptophan concentrations will lead to decreased availability of
      serotonin which finally increases the susceptibility for the development of mood
      disturbances and depression in the patients. Thus, the development of depression
      in cancer patients may result from chronic cellular immune stimulation. In
      conclusion, a more aggressive tumour rather than depression will be responsible
      for worse outcome of cancer patients and will be associated with a more drastic
      challenge of the immune system, as a side effect leading to neurotransmitter
      disturbances.

PMID- 10904431
TI  - Korotkoff sound: the cavitation hypothesis.
AB  - Blood pressure is universally measured by the auscultatory method, but the origin
      of the Korotkoff sounds remains controversial. A reproducible, brief and high
      amplitude signal, simultaneous to the Korotkoff sound, and instantly followed by
      the systolic wave, was recorded amongst ten healthy subjects by a pulsed Doppler
      examination during the deflation of the sphygmomanometer. A device simulating the
      brachial artery was also built in order to reproduce the high amplitude signal.
      It is explained by the cavitation phenomenon which takes place when the blood
      changes to vapor due to the release of the cuff pressure. With the incoming flow,
      the cavitation bubbles collapse and the energy is released as noise.

PMID- 10904432
TI  - Hierarchical cluster analysis as an approach for systematic grouping of diet
      constituents on basis of fatty acid, energy and cholesterol content: application
      on consumable lamb products.
AB  - The role of dietary fat in the etiology of chronic diseases is both a qualitative
      and a quantitative issue. The dietary fat intake is largely influenced by
      behavioral and social influences on food choice. Ongoing scientific research has
      led to dietary recommendations with main concerns being the percentage of
      saturated, essential fatty acids and cholesterol with respect to total energy
      intake. However, the compositional complexity of food choice constituting the
      diet is a critical concept complicating the interpretation of epidemiologic,
      clinical and laboratory evidence to define the role of dietary fat in the
      etiology of diseases. This study was conducted on the observation of the need to
      better systematically classify consumable food based on complex composition and
      lamb meat is randomly selected as a non-specific subset for application of
      hierarchical cluster analysis method to obtain the dendogram using average
      linkage. Data on fat composition of consumable lamb prepared by different methods
      was obtained from USDA Nutrient Database for Standart Reference. Using
      agglomerative hierarchical cluster analysis lamb meat was grouped into two main
      clusters among which one divided into two families of which each was subdivided
      into two subfamilies based on fatty acids, cholesterol and energy composition.
      Present work may be considered as a leading study to systematically classify
      larger food sets. As high fat foods are rich in flavor and overall palatability,
      the outcome of this study may lead to behaviorally more acceptable but healthier
      dietary replacements. Besides future use of the results obtained may reveal the
      effect of complex compositional dietary influences on health and disease and may
      have superiority to studies questioning individual dietary items. Furthermore,
      hieararchial cluster analysis may be used to cluster food including other
      compositional data in food items like amino acids, vitamins, carbohydrates, as
      well.

PMID- 10904433
TI  - Clock genes, feedback loops and their possible role in the etiology of bipolar
      disorders: an integrative model.
AB  - Clock genes, which are found in all higher organisms including humans, play a
      central role in the generation and control of circadian rhythms. For example, the
      amount of protein encoded by the per gene in mice oscillates with a circadian
      frequency. The per gene is activated by a constitutively expressed heterodimeric
      protein encoded by the bmal1 and clock genes, and this activation is suppressed
      by the PER protein itself. The negative feedback of the PER protein on the
      expression of the per gene provides a framework for a basic circadian
      autoregulatory loop in mammals. These elements of biomolecular feedback loops are
      interpreted within a system theory as an elementary behavioral cycle consisting
      of intentional programs (the per gene), environmental objects (the BMAL1-CLOCK
      heterodimer) and the experiential realization of the intended programs (the level
      of PER protein). This single model enables the deduction of disturbances, which
      can be transferred to the criteria of bipolar disorders. It is hypothesized that
      mutations in clock genes lead to disturbances in molecular feedback loops, which
      on a behavioral level could appear as bipolar disorders. Finally, some
      implications for research and treatment of bipolar disorders are discussed.

PMID- 10904434
TI  - Human body frequency modulation by 0.9% sodium chloride solutions: a new paradigm
      and perspective for human health.
AB  - This case study demonstrates that the normal human body frequency, which can be
      disturbed by electromagnetic influences of the environment, can be modulated by
      0.9% sodium chloride solutions (physiological saline) and that occurrence of
      allergic reactions have subsequently been suppressed as a result of this
      modulation. The use of distilled water as control showed no effect on occurrence
      of allergic reactions. Further observations on the growth of various plants in a
      greenhouse exposed to various geomagnetic fields support the previous
      observations on humans. The neutralization of electromagnetic influences on
      humans using 0.9% sodium chloride solution or by enclosure of plants within a
      copper wire Faraday cage resulting in a normal and uniform growth of plants as
      compared with disturbed and irregular growth in unenclosed controls, is
      demonstrated. These original observations propose a new strategy to suppress or
      prevent allergic reactions and possibly other effects observed in various human
      pathologies in relation to a disturbance of human body frequencies. It is
      hypothesized that the double helix structure of desoxyribonucleic acid (DNA)
      could be modified by environmental electromagnetic fields and that disresonance
      between the two chains of DNA could lead to the expression of specific pathology.

PMID- 10904435
TI  - Peri-operative aspirin can prevent post-operative ischemia and thrombosis.
AB  - Of the 30 million patients in the USA who undergo non-cardiac surgery every year,
      approximately 1.5 million suffer post-operative cardiovascular events. Surgical
      trauma and associated catecholamine release leads to platelet activation in the
      immediate post-operative period, as evidenced by a rise in circulating platelet
      release products. Platelet activation promotes platelet aggregation and
      hypercoagulability. Aspirin is widely used for its platelet inhibiting effects to
      prevent myocardial infarction and stroke. However, aspirin is not routinely
      started in the immediate peri-operative period, and even in high-risk patients
      already taking aspirin, aspirin is generally discontinued before elective surgery
      to improve intra-operative hemostasis. The risk-to-benefit ratios of
      administering vs withholding aspirin in the immediate peri-operative period have
      never been assessed and compared. We hypothesize that aspirin given pre-, intra-
      or immediately post-operatively will reduce post-operative ischemia and
      thrombotic events, including myocardial infarction and stroke, and that risk
      benefit analysis would favor the administration of aspirin. This hypothesis can
      and should be tested in a prospective, randomized trial.

PMID- 10904436
TI  - A neural network of obsessive- compulsive disorder: modelling cognitive
      disinhibition and neurotransmitter dysfunction.
AB  - While significant advances have been made in documenting both neurotransmitter
      and neuropsychological dysfunction in obsessive-compulsive disorder (OCD), there
      remains a need for theoretical models to account for their relationship. A neural
      network model of OCD was developed to provide a rigorous simulation of the
      relationship between the cognitive disinhibition and serotonin/dopamine
      dysfunction that characterize this disorder. An architecture-specific recurrent
      neural network of the Elman type was able to model the cognitive disinhibition
      that is apparent when OCD patients are compared with other anxiety disorder
      patients on a modified Stroop (Temporal Stroop) test, with OCD patients showing
      reduced negative priming (shorter reaction times to previously ignored stimuli).
      Lesions to either the color gain parameter (reflective of serotonergic
      dysfunction) or to the context gain parameter (reflective of dopaminergic
      dysfunction) resulted in decreased semantic negative priming. Neural network
      modelling provides a surprisingly coherent perspective of the psychobiology of
      OCD, simulating both reduced cognitive disinhibition as well as neurotransmitter
      dysfunction.

PMID- 10904437
TI  - Corpus callosum and cerebral laterality in a modular brain model.
AB  - This paper elaborates the function of corpus callosum in the brain model that
      contains encoding and modulating axons: the former encode data as presynaptic
      axonal 'on-off' patterns, and the latter help the former convert data into long
      term memory through the development of long-term potentiation and depression. It
      is hypothesized that callosal axons transfer data codes as interhemispheric
      memory. Bisection of corpus callosum cuts off interhemispheric data transfer and
      results in strange-hand syndrome, decreased attention and difficulties in
      acquiring new interdependent bimanual skills. While uniting two hemispheres for a
      unitary consciousness, corpus callosum contributes to two similar sets of
      integrated abstract memory, one in each hemisphere. Therefore, it takes bilateral
      cerebral lesions to manifest a failure of converting short-term memory into long
      term memory. The asymmetric callosal data transfer may correlate with cerebral
      laterality where a cerebral function, such as language, is conducted mainly in
      one hemisphere for the benefit of less interhemispheric data-traffic. Complete
      lateralization of a cerebral function is the rare occasion when the specialized
      neuron groups (modules) for that function all reside in one hemisphere. It is
      possible that many cerebral functions including language are incompletely
      lateralized, and corpus callosum links the non-lateralized modules with the
      lateralized ones. The more the cerebral lateralization, the fewer the non
      lateralized modules to be linked, and the smaller the corpus callosum.

PMID- 10904438
TI  - High-energy eccentric excimer laser angioplasty for debulking diffuse iIn-stent
      restenosis leads to better acute- and 6-month follow-up results.
AB  - BACKGROUND: Restenosis of diffuse in-stent stenosis (> 10 mm) treated with
      percutaneous transluminal coronary angioplasty (PTCA) is as high as 80%. The
      excessive tissue-hyperplasia led to debulking before PTCA. Because debulking is
      limited by the intensity and applicability of its use, the large debulking trials
      were criticized and showed no major benefit. Considering that a significantly
      greater diameter than its own diameter can be ablated by the Eccentric Excimer
      Laser (eccELCA), we evaluated its effectiveness and safety in a prospective
      study. METHODS: Thirty-nine patients with diffuse in-stent restenosis (3.4 +/-
      0.6 mm diameter; 14 +/- 9 mm in length) were treated by EccELCA followed by PTCA.
      In addition to clinical/angiographic target lesion revascularization (TLR) and
      major adverse cardiac events (MACE), the study endpoints were diameter stenosis
      (DS) and minimal lumen diameter (MLD), which were calculated before EccELCA,
      after EccELCA, after adjunctive PTCA and at 6-month follow-up. RESULTS:
      Procedural success was 99.8%. Delivered laser energy was 2,134 +/- 856 Joules. DS
      decreased from 84 +/- 14% to 23 +/- 11% after eccELCA (p = 0.0018) to 9 +/- 5%
      after PTCA (p = 0.001) and was 31 +/- 12% at follow-up (p = 0.0041). MLD
      increased from 0.7 +/- 0.2 mm to 2.2 +/- 0.4 mm after EccELCA (p = 0.0017), to
      2.7 +/- 0.4 mm after PTCA (p = 0.001) to 1.7 +/- 0.3 mm at follow-up (p =
      0.0049). Maximal balloon inflation pressure was 9.4 +/- 4.0 atmospheres. At
      follow-up angiography, TLR = 23.1%, clinical TLR = 12.8%, and MACE = 0%.
      CONCLUSION: Due to a greater debulking effect, additional lumen gain can be
      achieved immediately and at follow-up through the high-energy use of EccELCA for
      debulking and through the use of lower balloon inflation pressures for adjunctive
      PTCA. Clinical and angiographic TLR is significantly lower than other debulking
      techniques or PTCA alone and comparable with local irradiation therapy.

PMID- 10904439
TI  - A potential role for the eccentric laser in in-stent restenosis?

PMID- 10904440
TI  - Correlation of myocardial fractional flow reserve with thallium-201 SPECT imaging
      in intermediate-severity coronary artery lesions.
AB  - PURPOSE: The purpose of this study was to compare the measurements of fractional
      flow reserve of the myocardium (FFRmyo) with results of quantitative coronary
      angiography (QCA) and stress single-photon emission computed tomography thallium
      201 (SPECT 201Tl) imaging in patients with intermediate-severity coronary artery
      disease (ISCAD). METHODS: We prospectively evaluated 40 lesions of QCA-determined
      ISCAD in 30 patients (age, 53.3 +/- 10.2 years; 67% male) using a 0. 014 inch
      pressure wire during elective coronary angiography and compared the results with
      those of SPECT 201Tl performed within a week of angiography. RESULTS: There was a
      moderate negative correlation between percent diameter stenosis (%DS) and FFRmyo
      (53.1 +/- 13.4% and 0.75 +/- 0.09, respectively; r = -0.40; p = 0.01). Twenty-two
      out of 40 vascular territories (55%) were found to have perfusion defects (Group
      1) and 18 territories (45%) were found to be normal (Group 2). While QCA
      determined stenosis severity was not different between Group 1 and Group 2 (56 +/
      12% vs. 50 +/- 16%, respectively; p = 0.3), FFRmyo was found to be significantly
      different between the two groups (0.68 +/- 0.05 vs. 0.83 +/- 0.05, respectively;
      p = 0.001). When %DS and FFRmyo results were dichotomized as abnormal by 50% and
      < 0.75, respectively, and SPECT 201Tl was taken as the gold standard,
      sensitivity, specificity, positive predictive value and negative predictive value
      of %DS and FFRmyo were 0.55 vs. 0.91, 0.56 vs. 1.0, 0.60 vs. 1.0 and 0.50 vs. 0.
      90, respectively. CONCLUSION: While FFRmyo seems to accurately predict the
      presence of ischemia on SPECT 201Tl in patients with ISCAD, QCA does not reliably
      assess the physiologic impact of the same lesions.

PMID- 10904441
TI  - Fractional flow reserve: will pressure data replace angiography as the ultimate
      tool to guide our interventional therapy?

PMID- 10904442
TI  - A retrospective study of 6,671 patients comparing coronary stenting and balloon
      angioplasty.
AB  - OBJECTIVE: To determine whether coronary stenting, compared to percutaneous
      transluminal coronary angioplasty, reduces the incidence of five clinical
      endpoints during a six-month follow-up period. BACKGROUND: There is considerable
      debate concerning whether coronary stents improve clinical outcomes, especially
      given the rapid growth in the use of coronary stents and their economic impact.
      METHODS: Study population included a total of 6,671 consecutive patients at 32
      hospitals in 16 different states who underwent single or multi-vessel
      revascularization during 1997. Patients were divided into one of two groups:
      those who only underwent standard balloon angioplasty (PTCA) for all treated
      vessels and those who received coronary stents (STENT) in all treated vessels.
      RESULTS: STENT patients were significantly less likely to have emergency coronary
      artery bypass surgery (CABG) (p = 0.001) or die during initial procedure (p =
      0.034) but were more likely than PTCA patients to be treated for hematoma (p =
      0.002) and bradycardia (p = 0.004). After accounting for difference in patient
      characteristics, risk factors, procedure complications, and number of devices
      utilized, the estimated odds-ratio indicates that coronary stenting, compared to
      PTCA, significantly (p < 0.05) reduced adverse outcomes for only one clinical
      event, myocardial infarction. CONCLUSIONS: Compared to balloon angioplasty
      patients, coronary stent patients have no statistically significant differences
      in regard to additional percutaneous coronary intervention or coronary artery
      bypass during a six-month follow-up period. Since direct cardiac catheterization
      lab costs associated with coronary stenting is nearly 2.5 times greater than
      standard balloon angioplasty, our results suggest the cost-effectiveness of
      coronary stenting, especially for "hard" clinical outcomes, needs to be
      established.

PMID- 10904443
TI  - The subtle shades of death.

PMID- 10904445
TI  - Severe left main stem stenosis in a cardiac transplant recipient: successful
      treatment by coronary stenting.
AB  - A 58-year-old male underwent orthotopic cardiac transplantation for ischemic
      cardiomyopathy. At routine coronary angiography 2 years later, he was found to
      have severe concentric stenosis of the left main coronary artery but was
      asymptomatic. Revascularization was recommended on prognostic grounds and after
      discussion with his cardiac transplant surgeon, percutaneous coronary
      intervention with elective stenting was offered. This was performed successfully
      with a single stent and a good angiographic result was maintained 6 and 18 months
      later.

PMID- 10904444
TI  - Transradial coronary stent placement in a patient with severe idiopathic
      autoimmune thrombocytopenic purpura.
AB  - A 62-year-old man with refractory, idiopathic, autoimmune thrombocytopenic
      purpura developed unstable angina. Despite a platelet count of 3,000, transradial
      cardiac catheterization and coronary stent placement in the left anterior
      descending coronary artery were successfully performed. The patient was treated
      with clopidogrel for two weeks and aspirin for four weeks without adverse event.

PMID- 10904446
TI  - Successful angioplasty and stenting of anomalous right coronary artery using a 6
      French Left Judkins #5 guide catheter.
AB  - We describe the case of a 66-year-old female patient in whom percutaneous
      transluminal coronary angioplasty and stenting was performed in an anomalous
      right coronary artery arising from the ascending aorta above the non-coronary
      sinus of Valsalva using a 6 French Judkins JL5 catheter. The patient remained
      symptom free at 4-months follow-up.

PMID- 10904447
TI  - Right coronary artery occlusion caused by blunt trauma.
AB  - We describe the diagnostic and management dilemmas faced in the case of a thirty
      year-old woman without a prior cardiac history, who after a motor vehicle
      accident, was found to have persistent EKG changes in the inferior leads
      consistent with an acute injury pattern. The patient was ultimately thought to
      have trauma and subsequent occlusion of the right coronary artery.

PMID- 10904448
TI  - Successful radiofrequency catheter ablation of a right posterolateral bypass
      tract in a patient with Wolff-Parkinson-White syndrome after a previous failed
      ablative procedure: taking the high road.
AB  - A 16-year-old high school basketball player with symptomatic Wolff-Parkinson
      White syndrome underwent an unsuccessful radiofrequency catheter ablative
      procedure from the femoral venous approach. During this procedure, the patient
      received 30 applications of radiofrequency energy without injury to the accessory
      pathway. The patient was treated with flecinide 100 mg orally twice daily and
      rescheduled for a second ablative procedure via the right internal jugular venous
      approach. At the second session, prior to any right internal jugular venous
      applications, 3 additional applications were delivered via the right femoral
      venous approach using a different catheter, without success. A single
      radiofrequency energy application from the right internal jugular venous approach
      eliminated the bypass tract in approximately 2 seconds. The superior approach
      achieved a more stable catheter position thereby eliminating the bypass tract. In
      conclusion, an alternative plan of attack should be considered after multiple
      failures from a given approach. In other words, take the high road if you can't
      take the low road.

PMID- 10904449
TI  - Endovascular treatment of superficial femoral and popliteal arterial occlusive
      disease.

PMID- 10904450
TI  - Disclosure and prevention of medical errors. Committee on Bioethical Issues of
      the Medical Society of the State of New York.
AB  - Medical errors occur and are sometimes unavoidable. Physicians generally, but not
      always, have ethical and moral obligations to disclose their errors to the
      patient. Because common medical errors can be expected, physicians are obligated
      to work within health systems toward reducing systems flaws that promote errors.
      However, the obligations of physicians to disclose errors made by others are less
      clear. This article discusses the professional ethics involved in disclosing and
      preventing medical errors.

PMID- 10904451
TI  - Association between nonsteroidal anti-inflammatory drugs and upper
      gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies
      published in the 1990s.
AB  - BACKGROUND: In the last decades, studies have estimated the upper
      gastrointestinal tract bleeding/perforation (UGIB) risk associated with
      individual nonsteroidal anti-inflammatory drugs (NSAIDs). Later analyses have
      also included the effect of patterns of NSAID use, risk factors for UGIB, and
      modifiers of NSAID effect. METHODS: Systematic review of case-control and cohort
      studies on serious gastrointestinal tract complications and nonaspirin NSAIDs
      published between 1990 and 1999 using MEDLINE. Eighteen original studies were
      selected according to predefined criteria. Two researchers extracted the data
      independently. Pooled relative risk estimates were calculated according to
      subject and exposure characteristics. Heterogeneity of effects was tested and
      reasons for heterogeneity were considered. RESULTS: Advanced age, history of
      peptic ulcer disease, and being male were risk factors for UGIB. Nonsteroidal
      anti-inflammatory drug users with advanced age or a history of peptic ulcer had
      the highest absolute risks. The pooled relative risk of UGIB after exposure to
      NSAIDs was 3.8 (95% confidence interval, 3.6-4.1). The increased risk was
      maintained during treatment and returned to baseline once treatment was stopped.
      A clear dose response was observed. There was some variation in risk between
      individual NSAIDs, though these differences were markedly attenuated when
      comparable daily doses were considered. CONCLUSIONS: The elderly and patients
      with a history of peptic ulcer could benefit the most from a reduction in NSAID
      gastrotoxicity. Whenever possible, physicians may wish to recommend lower doses
      to reduce the UGIB risk associated with all individual NSAIDs, especially in the
      subgroup of patients with the greatest background risk.

PMID- 10904452
TI  - Depression is a risk factor for noncompliance with medical treatment: meta
      analysis of the effects of anxiety and depression on patient adherence.
AB  - BACKGROUND: Depression and anxiety are common in medical patients and are
      associated with diminished health status and increased health care utilization.
      This article presents a quantitative review and synthesis of studies correlating
      medical patients' treatment noncompliance with their anxiety and depression.
      METHODS: Research on patient adherence catalogued on MEDLINE and PsychLit from
      January 1, 1968, through March 31, 1998, was examined, and studies were included
      in this review if they measured patient compliance and depression or anxiety
      (with n>10); involved a medical regimen recommended by a nonpsychiatrist
      physician to a patient not being treated for anxiety, depression, or a
      psychiatric illness; and measured the relationship between patient compliance and
      patient anxiety and/or depression (or provided data to calculate it). RESULTS:
      Twelve articles about depression and 13 about anxiety met the inclusion criteria.
      The associations between anxiety and noncompliance were variable, and their
      averages were small and nonsignificant. The relationship between depression and
      noncompliance, however, was substantial and significant, with an odds ratio of
      3.03 (95% confidence interval, 1.96-4.89). CONCLUSIONS: Compared with
      nondepressed patients, the odds are 3 times greater that depressed patients will
      be noncompliant with medical treatment recommendations. Recommendations for
      future research include attention to causal inferences and exploration of
      mechanisms to explain the effects. Evidence of strong covariation of depression
      and medical noncompliance suggests the importance of recognizing depression as a
      risk factor for poor outcomes among patients who might not be adhering to medical
      advice.

PMID- 10904453
TI  - Physical activity, metabolic factors, and the incidence of coronary heart disease
      and type 2 diabetes.
AB  - OBJECTIVE: To examine the role of nonfasting serum insulin level and components
      of the insulin resistance syndrome in the relationship between physical activity
      and the incidence of coronary heart disease and type 2 diabetes. METHODS:
      Prospective study of 5159 men aged 40 to 59 years with no history of coronary
      heart disease, type 2 diabetes, or stroke drawn from general practices in 18
      British towns. During an average follow-up period of 16.8 years, there were 616
      cases of major coronary heart disease events (fatal and nonfatal) and 196
      incident cases of type 2 diabetes. RESULTS: After adjustment for potential
      confounders (lifestyle characteristics and preexisting disease), physical
      activity was inversely related to coronary heart disease rates, with the lowest
      rates in the men undertaking moderate physical activity and with no further
      benefit thereafter. For type 2 diabetes, risk decreased progressively with
      increasing levels of physical activity. Physical activity was associated with
      serum insulin level and with factors associated with insulin, ie, heart rate,
      hyperuricemia, diastolic blood pressure, and high-density lipoprotein cholesterol
      level, and with gamma-glutamyltransferase level, a possible marker of hepatic
      insulin resistance. Adjustment for insulin and associated factors made little
      difference to the relationship between physical activity and risk of coronary
      heart disease. By contrast, these factors together with gamma-glutamyltransferase
      level appear to explain a large proportion of the reduction in risk of type 2
      diabetes associated with physical activity. CONCLUSIONS: The relationship between
      physical activity and type 2 diabetes appears to be mediated by serum true
      insulin level and components of the insulin resistance syndrome. However, these
      factors do not appear to explain the inverse relationship between physical
      activity and coronary heart disease.

PMID- 10904454
TI  - Associations of general and abdominal obesity with multiple health outcomes in
      older women: the Iowa Women's Health Study.
AB  - BACKGROUND: Recent clinical guidelines on the health risks of obesity use body
      mass index (BMI; calculated as weight in kilograms divided by the square of
      height in meters) and waist circumference, but the waist-hip ratio may provide
      independent information. METHODS: To assess the joint and relative associations
      of BMI, waist circumference, and waist-hip ratio with multiple disease end
      points, we conducted a prospective cohort study of 31,702 Iowa women, aged 55 to
      69 years and free of cancer, heart disease, and diabetes, assembled by random
      sampling and mail survey in 1986. Study end points were total and cause-specific
      mortality and incidence of site-specific cancers and self-reported diabetes,
      hypertension, and hip fracture over 11 to 12 years. RESULTS: The waist-hip ratio
      was the best anthropometric predictor of total mortality, with the multivariable
      adjusted relative risk for quintile 5 vs 1 of 1.2 (95% confidence interval, 1.1
      1.4), compared with 0.91 (95% confidence interval, 0.8-1.0) for BMI and 1.1 (95%
      confidence interval, 1.0-1. 3) for waist circumference. The waist-hip ratio was
      also associated positively with mortality from coronary heart disease, other
      cardiovascular diseases, cancer, and other causes. The waist-hip ratio was
      associated less consistently than BMI or waist circumference with cancer
      incidence. All anthropometric indexes were associated with incidence of diabetes
      and hypertension. For example, women simultaneously in the highest quintiles of
      BMI and waist-hip ratio had a relative risk of diabetes of 29 (95% confidence
      interval, 18-46) vs. women in the lowest combined quintiles. CONCLUSION: The
      waist-hip ratio offers additional prognostic information beyond BMI and waist
      circumference.

PMID- 10904455
TI  - Discrepancies in the use of medications: their extent and predictors in an
      outpatient practice.
AB  - BACKGROUND: Misuse of medications is a major cause of morbidity and mortality.
      Few studies have examined the frequency of, and factors associated with,
      discrepancies between what doctors prescribe and what patients take in actual
      practice. PATIENTS AND METHODS: Patients' medication bottles and their reported
      use of medications were compared with physicians' records of outpatients seen
      between November 1997 and February 1998 in a private practice affiliated with an
      academic medical center in Boston, Mass. Three hundred twelve patients from the
      practices of 5 cardiologists and 2 internists who were returning for their
      routine follow-up visits were included. MAIN OUTCOME MEASURE: The presence of
      discrepancies based on comparing medication bottles with medical records.
      RESULTS: Discrepancies were present in 239 patients (76%). The 545 discrepancies
      in these patients were the result of patients taking medications that were not
      recorded (n = 278 [51%]); patients not taking a recorded medication (n = 158
      [29%]); and differences in dosage (n = 109 [20%]). Overall, discrepancies were
      randomly distributed among different drugs and discrepancy types with no
      discernible pattern. On multivariate analysis, patient age and number of recorded
      medications were the 2 most significant predictors of medication discrepancy.
      CONCLUSIONS: Discrepancies among recorded and reported medications were common
      and involved all classes of medications, including cardiac and prescription
      drugs. Older age and polypharmacy were the most significant correlates of
      discrepancy. The pervasiveness of discrepancies can have significant health care
      implications, and action is urgently needed to address their causes. Such action
      would likely have a positive impact on patient care.

PMID- 10904456
TI  - Epidemiology of restless legs symptoms in adults.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a disorder characterized by sleep
      disrupting unpleasant leg sensations, often accompanied by daytime behavioral
      problems. Treatment for this condition is available, but it is suspected that
      most instances of RLS remain undiagnosed. The goal of this investigation was to
      assess the prevalence and health status correlates of restless legs symptoms
      (hereinafter referred to as restless legs) in the general population. METHODS: A
      question reflecting the clinical features of RLS was added to the 1996 Kentucky
      Behavioral Risk Factor Surveillance Survey. Data on the frequency of experiencing
      restless legs, self-rated general and mental health status, demographics, and
      behavioral risk factors were collected by telephone interview from 1803 men and
      women, 18 years and older. RESULTS: Experiencing restless legs 5 or more nights
      per month was reported by 3% of participants aged 18 to 29 years, 10% of those
      aged 30 to 79 years, and 19% of those 80 years and older. The age-adjusted
      prevalence for Kentucky adults is 10.0%; prevalence did not vary significantly by
      sex. The adjusted odds ratios (95% confidence intervals) for restless legs and
      diminished general health and poor mental health status were 2.4 (1.4-4.0) and
      3.1 (2.0-4.6), respectively. Restless legs were significantly associated with
      increased age and body mass index, lower income, smoking, lack of exercise, low
      alcohol consumption, and diabetes. CONCLUSIONS: The prevalence of restless legs
      in the general adult population is high. Restless legs may be associated with
      decreased well-being, emphasizing the need for further research and greater
      medical recognition of this condition.

PMID- 10904457
TI  - Continuously increasing number and incidence of fall-induced, fracture
      associated, spinal cord injuries in elderly persons.
AB  - BACKGROUND: Although osteoporosis, falls, and fractures among older adults are
      said to be a continuously increasing public health problem, reliable
      epidemiological information on their secular trends is very limited. OBJECTIVE:
      To determine the current trend in the number and incidence of fall-induced,
      fracture-associated, spinal cord injuries in a typical white population (Finland,
      a country with about 5 million inhabitants). METHODS: All Finns aged 50 years or
      older who were admitted to hospitals from January 1, 1970, through December 31,
      1995, for primary treatment of an acute fall-induced, fracture-associated, spinal
      cord injury were selected from the National Hospital Discharge Register. Similar
      patients aged 20 through 39 years served as a reference group. In each year of
      the study, the number and the age-specific and age-adjusted incidences of
      injuries were expressed as the number of patients per 100,000 persons. RESULTS:
      The total number of fall-induced, fracture-associated, spinal cord injuries of
      Finnish older adults increased considerably during the study period, from 60 in
      1970 to 419 in 1995 (an average increase of 24% annually). The corresponding
      injury incidence was 5 in 1970 and 27 in 1995. The age-adjusted incidence of
      these injuries also increased from 1970 to 1995: in women, from 5 to 29, and in
      men, from 7 to 17 (relative increases were 480% and 143%, respectively). In the
      reference group, no trend changes by time were observed. CONCLUSIONS: In Finnish
      persons aged 50 years or older, the number of fall-induced, fracture-associated,
      spinal cord injuries shows a rise with a rate that cannot be explained merely by
      demographic changes. The finding shows an increasing influence of osteoporosis
      and falls on health and well-being of our older adults, and therefore, vigorous
      preventive measures are needed to control this development.

PMID- 10904458
TI  - A randomized trial of improved weight loss with a prepared meal plan in
      overweight and obese patients: impact on cardiovascular risk reduction.
AB  - OBJECTIVE: To assess the long-term effects of a prepackaged, nutritionally
      complete, prepared meal plan compared with a usual-care diet (UCD) on weight loss
      and cardiovascular risk factors in overweight and obese persons. DESIGN: In this
      randomized multicenter study, 302 persons with hypertension and dyslipidemia (n =
      183) or with type 2 diabetes mellitus (n = 119) were randomized to the nutrient
      fortified prepared meal plan (approximately 22% energy from fat, 58% from
      carbohydrate, and 20% from protein) or to a macronutrient-equivalent UCD. MAIN
      OUTCOME MEASURES: The primary outcome measure was weight change. Secondary
      measures were changes in blood pressure or plasma lipid, lipoprotein, glucose, or
      glycosylated hemoglobin levels; quality of life; nutrient intake; and dietary
      compliance. RESULTS: After 1 year, weight change in the hypertension/dyslipidemia
      group was -5.8+/-6.8 kg with the prepared meal plan vs -1.7+/-6.5 kg with the UCD
      plan (P<.001); for the type 2 diabetes mellitus group, the change was -3.0+/-5.4
      kg with the prepared meal plan vs -1.0+/-3.8 kg with the UCD plan (P<.001) (data
      given as mean +/- SD). In both groups, both interventions improved blood
      pressure, total and low-density lipoprotein cholesterol levels, glycosylated
      hemoglobin level, and quality of life (P<.02); in the diabetic group, the glucose
      level was reduced (P<.001). Compared with those in the UCD group, participants
      with hypertension/dyslipidemia in the prepared meal plan group showed greater
      improvements in total (P<.01) and high-density lipoprotein (P<.03) cholesterol
      levels, systolic blood pressure (P<.03), and glucose level (P<.03); in
      participants with type 2 diabetes mellitus, there were greater improvements in
      glucose (P =.046) and glycosylated hemoglobin (P<.02) levels. The prepared meal
      plan group also showed greater improvements in quality of life (P<.05) and
      compliance (P<.001) than the UCD group. CONCLUSIONS: Long-term dietary
      interventions induced significant weight loss and improved cardiovascular risk in
      high-risk patients. The prepared meal plan simultaneously provided the simplicity
      and nutrient composition necessary to maintain long-term compliance and to reduce
      cardiovascular risk.

PMID- 10904459
TI  - Effects of hormone replacement therapy on bone mineral density in postmenopausal
      women with primary hyperparathyroidism: four-year follow-up and comparison with
      healthy postmenopausal women.
AB  - BACKGROUND: Long-term treatment of patients with asymptomatic primary
      hyperparathyroidism remains controversial, but the presence of osteoporosis is
      regarded as an indication for parathyroidectomy. Hormone replacement therapy
      (HRT) is a possible alternative therapy in osteopenic postmenopausal women with
      the disorder, and results of short-term studies suggest a beneficial effect on
      bone mass comparable to that achieved by parathyroidectomy. Longer-term data are
      required to further assess the efficacy of this treatment in chronic stable
      primary hyperparathyroidism. METHODS: We report the results of the extension from
      2 to 4 years of a randomized, placebo-controlled trial of HRT in postmenopausal
      women with primary hyperparathyroidism. Of 23 postmenopausal women with primary
      hyperparathyroidism, 11 received active HRT with conjugated equine estrogen,
      0.625 mg/d, and medroxyprogesterone acetate, 5 mg/d, and 12 received placebo.
      Bone mineral density was measured throughout the skeleton at 6-month intervals
      using dual-energy x-ray absorptiometry in these women and in 50 normocalcemic age
      matched control subjects. None of the 23 patients withdrew during the extension
      period. RESULTS: Changes in bone mineral density were more positive in those
      taking HRT than placebo, with the between-group differences at 4 years being 4.6%
      in the total body, 7.5% in the lumbar spine, 7.4% in the femoral neck, 8.2% in
      the femoral trochanter, 6.8% in the legs, and 7.0% in the forearm (P<.01). At
      skeletal sites composed predominantly of cortical bone, there was a progressive
      divergence of the 2 groups. Biochemical markers of bone turnover remained lower
      throughout the study in women taking HRT. When rates of bone loss were compared
      between the placebo group and healthy women of comparable age, bone loss tended
      to be more marked throughout the skeleton in women with hyperparathyroidism, but
      only in the total body and its legs subregion was this difference significant.
      CONCLUSIONS: Hormone replacement therapy is efficacious in the long-term
      management of osteopenia in postmenopausal women with primary hyperparathyroidism
      and thus represents an important new therapeutic option for asymptomatic patients
      who do not have other indications for surgery. Bone loss seems to be accelerated
      in untreated primary hyperparathyroidism.

PMID- 10904460
TI  - Identifying patients for weight-loss treatment: an empirical evaluation of the
      NHLBI obesity education initiative expert panel treatment recommendations.
AB  - BACKGROUND: The NHLBI (National Heart, Lung, and Blood Institute) Obesity
      Education Initiative Expert Panel recently proposed that clinicians and other
      health care professionals use a new treatment algorithm to identify patients for
      weight-loss treatment. In addition to the usual assessment of body mass index
      (BMI, calculated as weight in kilograms divided by the square of height in
      meters), the new algorithm includes the assessment of abdominal obesity (as
      measured by waist circumference) and other cardiovascular disease (CVD) risk
      factors. METHODS: We examined the percentage of adults meeting the criteria of
      the panel's treatment algorithm: BMI > or =30 or ?[BMI, 25.0-29.9 or waist
      circumference >88 cm (women) >102 cm (men)] and > or = 2 CVD risk factors? in a
      sample of 2844 black, 2754 Mexican American, and 3504 white adults, aged 25 to 64
      years, from the Third National Health and Nutrition Examination Survey, 1988
      1994. RESULTS: Across ethnic groups, more than 98% of adults (normal weight,
      overweight, and obese) received the same treatment recommendations using the
      panel's algorithm and an algorithm based only on BMI and CVD risk factors,
      without waist circumference. For normal-weight adults, almost none (0.0%-1.8%)
      had a large waist circumference as defined above and 2 or more CVD risk factors.
      Using the usual criterion of a BMI of 30 or higher, a substantial percentage of
      at-risk overweight women and men (BMI, 25.0-29.9) with 2 or more CVD risk factors
      were missed (8.4% and 19.3%, respectively). CONCLUSIONS: Despite the potential
      importance of abdominal obesity as a CVD risk factor, these results challenge the
      clinical utility of including waist circumference in this new algorithm and
      suggest that using BMI and CVD risk factors may be sufficient.

PMID- 10904461
TI  - Effects of walking training on weight maintenance after a very-low-energy diet in
      premenopausal obese women: a randomized controlled trial.
AB  - BACKGROUND: Maintenance of weight loss is a core problem in the treatment of
      obesity. Physical activity may improve maintenance and metabolic risk factors
      associated with obesity. HYPOTHESES: (1) A walking training program of moderate
      intensity, started after weight reduction by a very-low-energy diet, improves
      maintenance of weight loss and obesity-related metabolic disorders; and (2) the
      effect of the training program is related to the prescribed amount of physical
      activity, ie, a higher amount (energy expenditure) leads to more favorable
      results. METHODS: The participants were premenopausal women with a mean body mass
      index of 34.0 kg/m(2). Eighty-two participants were randomized to this study; 74
      participated in the follow-up assessment. A 12-week weight reduction by mostly a
      very-low-energy diet was followed by a 40-week maintenance program randomized in
      3 groups: a control group with no increase in habitual exercise and with
      counseling on diet and relapse prevention; a walk-1 group, with a walking program
      targeted to expend 4.2 MJ/wk and diet counseling; and a walk-2 group, with a
      walking program of 8. 4 MJ/wk and diet counseling. Random permuted blocks within
      strata were used, with weight loss (in 3 classes) as the stratifying factor.
      After the intervention, the subjects were followed up for 2 years. MAIN OUTCOME
      MEASURES: Primary outcomes were body weight, fat mass, and waist circumference at
      the 2-year follow-up. Secondary outcomes were the levels of serum lipoproteins
      and lipids, plasma glucose, insulin, and blood pressure. RESULTS: The mean weight
      loss after weight reduction was 13.1 kg. The main outcome variables remained
      stable during the maintenance program, but increased during the follow-up period.
      Compared with the end of weight reduction, weight regain at the 2-year follow-up
      was 3.5 kg less (95% confidence interval, 0.2-6.8) and waist circumference regain
      3.8 cm less (95% confidence interval, 0.3-7.3) in the walk-1 group vs controls.
      The secondary outcomes showed a partial relapse during the maintenance program,
      and a further regain during the follow-up period. CONCLUSIONS: Inclusion of a
      walking program of moderate training regimen into a weight maintenance program
      improved maintenance of losses in weight and waist circumference.

PMID- 10904462
TI  - Efficacy and safety of sibutramine in obese white and African American patients
      with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial.
AB  - BACKGROUND: Obesity is a highly prevalent medical condition and is commonly
      accompanied by hypertension. This study assessed the efficacy and safety of
      treatment with sibutramine hydrochloride for promoting and maintaining weight
      loss in obese patients with controlled hypertension, including a subset analysis
      of African American patients. PATIENTS AND METHODS: Obese patients with a body
      mass index (BMI, calculated as weight in kilograms divided by the square of
      height in meters) between 27 and 40 and a history of hypertension controlled with
      a calcium channel blocker (with or without concomitant thiazide diuretic
      treatment) were randomized to receive sibutramine (n = 150) or placebo (n = 74)
      with minimal behavioral intervention for 52 weeks. African Americans constituted
      36% of enrolled patients. Efficacy assessments were body weight and related
      parameters (BMI and waist and hip circumferences), metabolic parameters (serum
      levels of triglycerides, high-density lipoprotein cholesterol [HDL-C], low
      density lipoprotein cholesterol [LDL-C], total cholesterol, glucose, and uric
      acid), and quality-of-life measures. Safety assessments included recording of
      blood pressure, pulse rate, adverse events, and reasons for discontinuation.
      RESULTS: For patients receiving sibutramine, weight loss occurred during the
      first 6 months of the trial and was maintained to the end of the 12-month
      treatment period. Among patients receiving sibutramine, 40.1% lost 5% or more of
      body weight (5% responders) and 13.4% lost 10% or more of body weight (10%
      responders) compared with 8.7% and 4.3% of patients in the placebo group,
      respectively (P<.05). Changes in body weight were similar among African Americans
      and whites. Sibutramine-induced weight loss was associated with significant
      improvements in serum levels of triglycerides, HDL-C, glucose, and uric acid.
      Waist circumference and quality-of-life measures also improved significantly in
      patients receiving sibutramine. Sibutramine-treated patients had small but
      statistically significant mean increases in diastolic blood pressure (2.0 mm Hg)
      and pulse rate (4.9 beats/min) compared with placebo-treated patients (-1.3 mm Hg
      and 0.0 beats/min; P<.05); these changes were similar among African Americans and
      whites. Most adverse events were mild to moderate in severity and transient. The
      most common adverse event resulting in discontinuation among patients receiving
      sibutramine was hypertension (5.3% of patients receiving sibutramine vs 1.4% of
      patients receiving placebo). CONCLUSIONS: In obese patients with controlled
      hypertension, sibutramine was an effective and well-tolerated treatment for
      weight loss and maintenance. Sibutramine-induced weight loss resulted in
      improvements in serum levels of triglycerides, HDL-C, uric acid, and glucose, and
      in waist circumference and quality-of-life measures. Blood pressure and heart
      rate increased by a small amount. Efficacy and safety profiles for sibutramine
      among African American and white obese patients with controlled hypertension were
      similar.

PMID- 10904463
TI  - The relationship between longitudinal declines in dehydroepiandrosterone sulfate
      concentrations and cognitive performance in older men.
AB  - BACKGROUND: The observation that dehydroepiandrosterone (DHEA) concentrations
      decrease markedly with age has led to the hypothesis that declining DHEA
      concentrations may contribute to age-related changes in cognition. In the United
      States, DHEA is widely available as an over-the-counter supplement that
      individuals are using in an effort to ameliorate age-related cognitive and
      physical changes. OBJECTIVE: To investigate the relationship between age
      associated decreases in endogenous DHEA sulfate (DHEA-S) concentrations and
      declines in neuropsychological performance in a prospective, longitudinal study.
      METHODS: The subjects were 883 men from a community-dwelling volunteer sample in
      the Baltimore Longitudinal Study of Aging. The men were aged 22 to 91 years at
      the initial visit, and they were followed up for as long as 31 years (mean, 11.
      55 years), with biennial reassessments of multiple cognitive domains and
      contemporaneous measurement of serum DHEA-S concentrations. Outcome measures were
      the results of cognitive tests of verbal and visual memory, 2 tests of mental
      status, phonemic and semantic word fluency tests, and measures of visuomotor
      scanning and attention. Serum DHEA-S concentrations were determined by standard
      radioimmunoassay. RESULTS: Neither the rates of decline in mean DHEA-S
      concentrations nor the mean DHEA-S concentrations within individuals were related
      to cognitive status or cognitive decline. A comparison between the highest and
      lowest DHEA-S quartiles revealed no cognitive differences, despite the fact that
      these groups differed in endogenous DHEA-S concentration by more than a factor of
      4 for a mean duration of 12 years. CONCLUSION: Our longitudinal results augment
      those of previous prospective studies by suggesting that the decline in
      endogenous DHEA-S concentration is independent of cognitive status and cognitive
      decline in healthy aging men.

PMID- 10904464
TI  - Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to
      surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized
      comparison. The North American Fragmin Trial Investigators.
AB  - BACKGROUND: Based on the current understanding that venous thrombosis starts
      perioperatively, administration of just-in-time low-molecular-weight heparin
      immediately before or in close proximity after hip arthroplasty may be more
      effective than usual clinical practice. METHODS: We performed a randomized,
      double-blind trial comparing subcutaneous dalteparin sodium given once daily
      immediately before or early after surgery with the use of postoperative warfarin
      sodium in 1472 patients undergoing elective hip arthroplasties. The primary end
      point was deep vein thrombosis detected using contrast venography performed after
      surgery (mean, 5. 7 days) in each group. RESULTS: The frequencies of deep vein
      thrombosis for patients with interpretable venograms receiving preoperative and
      postoperative dalteparin for all deep vein thrombosis were 36 (10.7%) of 337
      (P<.001) and 44 (13.1%) of 336 (P<.001), respectively, vs 81 (24.0%) of 338 for
      warfarin; for proximal deep vein thrombosis, 3 (0.8%) of 354 (P =.04) and 3
      (0.8%) of 358 (P =.03), respectively, vs 11 (3.0%) of 363. Relative risk
      reductions for the dalteparin groups ranged from 45% to 72%. Symptomatic thrombi
      were less frequent in the preoperative dalteparin group (5/337 patients [1.5%])
      vs the warfarin group (15/338 patients [4.4%]) (P =.02). Serious bleeding was
      similar among groups. Increased major bleeding at the surgical site was observed
      for patients receiving preoperative dalteparin vs warfarin (P =.01). CONCLUSIONS:
      A modified dalteparin regimen in close proximity to surgery resulted in
      substantive risk reductions for all and proximal deep vein thrombosis, compared
      with warfarin therapy. Such findings have not been observed with low-molecular
      weight heparin therapy commenced 12 hours preoperatively or 12 to 24 hours
      postoperatively vs oral anticoagulants. Increased major but not serious bleeding
      occurred in patients receiving preoperative dalteparin. Dalteparin therapy
      initiated postoperatively provided superior efficacy vs warfarin without
      significantly increased overt bleeding.

PMID- 10904465
TI  - Low-molecular-weight heparin prophylaxis using dalteparin extended out-of
      hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty
      patients: a double-blind, randomized comparison. North American Fragmin Trial
      Investigators.
AB  - BACKGROUND: No randomized trials have directly evaluated the need for extended
      out-of-hospital thromboprophylaxis for patients who have hip arthroplasty in the
      United States or Canada. The uncertainty as to the need for extended prophylaxis
      in North American patients is complicated by early hospital discharge, resulting
      in a short thromboprophylaxis interval. METHODS: To resolve this uncertainty, we
      performed a randomized double-blind trial in 569 patients who underwent hip
      arthroplasty comparing the use of dalteparin sodium started immediately before
      surgery or early after surgery and extended out-of-hospital to an overall
      interval of 35 days with the use of warfarin sodium in-hospital and placebo out
      of-hospital. RESULTS: For patients with interpretable venograms in the
      preoperative, postoperative, and combined dalteparin groups, new proximal vein
      thrombosis out-of-hospital was observed in 1.3%, 0. 7% (P =.04), and 1.0% (P
      =.02) of patients, respectively, compared with 4.8% in the in-hospital
      warfarin/out-of-hospital placebo group. The respective overall cumulative
      frequencies of all deep vein thrombosis were 30 (17.2%) of 174 patients (P<.001),
      38 (22.2%) of 171 (P =.003), and 68 (19.7%) of 345 (P<.001) in the dalteparin
      groups compared with 69 (36.7%) of 188 for the in-hospital warfarin/out-of
      hospital placebo group. For proximal deep vein thrombosis, the respective
      frequencies were 5 (3.1%) of 162 (P =.02), 3 (2.0%) of 151 (P =.007), and 8
      (2.6%) of 313 (P =.002) compared with 14 (9.2%) of 153. No major bleeding
      occurred during the extended prophylaxis interval. CONCLUSIONS: Extended
      dalteparin prophylaxis resulted in significantly lower frequencies of deep vein
      thrombosis compared with in-hospital warfarin therapy. Despite in-hospital
      thromboprophylaxis, patients having hip arthroplasty in the United States and
      Canada remain at moderate risk out-of-hospital. The number needed to treat
      provides a public health focus; only 24 to 28 patients require extended
      prophylaxis to prevent 1 new out-of-hospital proximal vein thrombosis. Recent
      studies demonstrate that asymptomatic deep vein thrombi cause the postphlebitic
      syndrome; thus, extended out-of-hospital prophylaxis will lessen the burden to
      both the patient and society.

PMID- 10904466
TI  - Successful treatment of massive hemoptysis in acute leukemia with recombinant
      factor VIIa.

PMID- 10904467
TI  - Diabetes is associated with longer survival rates in patients with malignant
      tumors.

PMID- 10904468
TI  - D-dimer and pulmonary embolism: is there a good interpretation?

PMID- 10904469
TI  - Silent pulmonary embolism.

PMID- 10904472
TI  - On meningococcal disease, its prognosis, and undernotification of the Public
      Health Service.

PMID- 10904473
TI  - Oral antibiotics and outcome in meningococcemia.

PMID- 10904470
TI  - Drug-induced allergic cytopenia: in vitro confirmation by the lymphocyte
      transformation test.

PMID- 10904475
TI  - Lying for patients may be a violation of federal Law.

PMID- 10904476
TI  - Little white lies.

PMID- 10904477
TI  - The factuality of health records.

PMID- 10904479
TI  - Nonulcer dyspepsia and helicobacter pylori infection.

PMID- 10904481
TI  - Medical Students' opinions of euthanasia and physician-assisted suicide in Italy.

PMID- 10904483
TI  - JAMA 100 years ago: BLOOD EXAMINATION

PMID- 10904482
TI  - A piece of my mind: missed connections.

PMID- 10904484
TI  - Characteristics and management of postpolio syndrome.

PMID- 10904485
TI  - International conference considers health needs of the rural elderly.

PMID- 10904487
TI  - JCAHO pain management standards are unveiled. Joint Commission on Accreditation
      of Healthcare Organizations.

PMID- 10904489
TI  - Quick uptakes: breast cancer vaccine

PMID- 10904488
TI  - Quick uptakes: liver cells from bone marrow

PMID- 10904491
TI  - Quick uptakes: morning-after consequences

PMID- 10904490
TI  - Quick uptakes: online risk assessment expands

PMID- 10904493
TI  - Beta-blockade for patients with heart failure.

PMID- 10904492
TI  - Beta-blockade for patients with heart failure.

PMID- 10904494
TI  - beta-blockade for patients with heart failure

PMID- 10904495
TI  - How often should patients with diabetes be screened for retinopathy?

PMID- 10904496
TI  - How often should patients with diabetes be screened for retinopathy?

PMID- 10904497
TI  - How often should patients with diabetes be screened for retinopathy?

PMID- 10904498
TI  - How often should patients with diabetes Be screened for retinopathy?

PMID- 10904499
TI  - Cost-effectiveness of pneumococcal vaccine.

PMID- 10904500
TI  - Cost-effectiveness of pneumococcal vaccine.

PMID- 10904501
TI  - Cost-effectiveness of pneumococcal vaccine

PMID- 10904503
TI  - Measuring level of sedation in the intensive care unit

PMID- 10904502
TI  - Measuring level of sedation in the intensive care unit.

PMID- 10904504
TI  - The politics of cancer

PMID- 10904505
TI  - JAMA 100 years ago and osteopathy

PMID- 10904506
TI  - The Internet as a newly emerging risk environment for sexually transmitted
      diseases.
AB  - CONTEXT: Transmission of sexually transmitted diseases (STDs) such as human
      immunodeficiency virus (HIV) infection is associated with unprotected sex among
      multiple anonymous sex partners. The role of the Internet in risk of STDs is not
      known. OBJECTIVE: To compare risk of STD transmission for persons who seek sex
      partners on the Internet with risk for persons not seeking sex partners on the
      Internet. DESIGN: Cross-sectional survey conducted September 1999 through April
      2000. SETTING AND PARTICIPANTS: A total of 856 clients of the Denver Public
      Health HIV Counseling and Testing Site in Colorado. MAIN OUTCOME MEASURES: Self
      report of logging on to the Internet with the intention of finding sex partners;
      having sex with partners who were originally contacted via the Internet; number
      of such partners and use of condoms with them; and time since last sexual contact
      with Internet partners, linked to HIV risk assessment and test records. RESULTS:
      Of the 856 clients, most were white (77. 8%), men (69.2%), heterosexual (65.3%),
      and aged 20 to 50 years (84. 1%). Of those, 135 (15.8%) had sought sex partners
      on the Internet, and 88 (65.2%) of these reported having sex with a partner
      initially met via the Internet. Of those with Internet partners, 34 (38.7%) had 4
      or more such partners, with 62 (71.2%) of contacts occurring within 6 months
      prior to the client's HIV test. Internet sex seekers were more likely to be men
      (P<.001) and homosexual (P<.001) than those not seeking sex via the Internet.
      Internet sex seekers reported more previous STDs (P =.02); more partners
      (P<.001); more anal sex (P<.001); and more sexual exposure to men (P<.001), men
      who have sex with men (P<.001), and partners known to be HIV positive (P<.001)
      than those not seeking sex via the Internet. CONCLUSIONS: Seeking sex partners
      via the Internet was a relatively common practice in this sample of persons
      seeking HIV testing and counseling (representative of neither Denver nor the
      overall US population). Clients who seek sex using the Internet appear to be at
      greater risk for STDs than clients who do not seek sex on the Internet. JAMA.
      2000;284:443-446

PMID- 10904507
TI  - Tracing a syphilis outbreak through cyberspace.
AB  - CONTEXT: A recent outbreak of syphilis among users of an Internet chat room
      challenged traditional methods of partner notification and community education
      because locating information on sexual partners was limited to screen names and
      privacy concerns precluded identifying sexual partners through the Internet
      service provider. OBJECTIVES: To determine the association of Internet use and
      acquisition of syphilis and to describe innovative methods of partner
      notification in cyberspace. DESIGN, SETTING, AND PATIENTS: Outbreak investigation
      conducted at the San Francisco (Calif) Department of Public Health (SFDPH) in
      June-August 1999 of 7 cases of early syphilis among gay men linked to an online
      chat room; case-control study of 6 gay men with syphilis reported to SFDPH in
      July-August 1999 (cases) and 32 gay men without syphilis who presented to a city
      clinic in April-July 1999 (controls). MAIN OUTCOME MEASURES: Association of
      syphilis infection with Internet use, Internet use among cases vs controls, and
      partner notification methods and partner evaluation indexes. RESULTS: During the
      outbreak, cases were significantly more likely than controls to have met their
      sexual partners through use of the Internet (67% vs 19%; odds ratio, 8.7; P
      =.03). We notified and confirmed testing for 42% of named partners; the mean
      number of sexual partners medically evaluated per index case was 5.9.
      CONCLUSIONS: In this study, meeting sexual partners through the Internet was
      associated with acquisition of syphilis among gay men. Public health efforts must
      continually adapt disease control procedures to new venues, carefully weighing
      the rights to privacy vs the need to protect public health. JAMA. 2000;284:447
      449

PMID- 10904508
TI  - The natural history of hepatitis C virus infection: host, viral, and
      environmental factors.
AB  - CONTEXT: Hepatitis C virus (HCV) infection may resolve (viral clearance), persist
      without complications, or cause end-stage liver disease (ESLD). The frequency and
      determinants of these outcomes are poorly understood. OBJECTIVE: To assess the
      incidence and determinants of viral clearance and ESLD among persons who acquired
      HCV infection from injection drug use. DESIGN AND SETTING: Community-based
      prospective cohort study with enrollment in 1988-1989 and a median follow-up of
      8.8 years. SUBJECTS: A total of 1667 persons aged 17 years or older with a
      history of injection drug use and an HCV antibody-positive test result during
      follow-up. MAIN OUTCOME MEASURES: Viral clearance was assessed in a subset of 919
      patients and defined as failure to detect HCV RNA in at least 2 consecutive
      samples collected 5 or more months apart. End-stage liver disease was assessed at
      semiannual visits and by review of medical records and death certificates and
      defined by the presence of ascites, esophageal varices, or hepatic
      encephalopathy, or when ESLD was stated as a cause of death. RESULTS: Viral
      clearance was observed in 90 persons who were compared with 722 with persistent
      viremia, while the viremia of 107 was not resolved. Viral clearance occurred more
      often in nonblacks (adjusted odds ratio [OR], 5.15; 95% confidence interval [CI],
      2.60-10.17) and those not infected with human immunodeficiency virus (HIV)
      (adjusted OR, 2.19; 95% CI, 1.26-3.47). Forty cases of ESLD were observed
      throughout follow-up (incidence, 3.1 per 1000 person-years). In a multivariate
      model, risk of ESLD was higher for persons aged 38 years or older at enrollment
      (adjusted relative incidence, 3.67; 95% CI, 1.96-6.88) and who reported ingestion
      of more than 260 g of alcohol per week (adjusted relative incidence, 3.60; 95%
      CI, 1.73-7.52). Of 210 patients without ESLD randomly selected for biopsy, only 2
      had cirrhosis. CONCLUSIONS: Our results indicate that although HCV infection can
      be self-limited or associated with ESLD, the majority of adults have persistent
      viremia without clinically demonstrable liver disease. Further research is needed
      to explain the less frequent clearance of HCV infection among black persons and
      to improve utilization of treatment for those infected in the context of
      injection drug use. JAMA. 2000;284:450-456

PMID- 10904509
TI  - Cardiac-specific troponin I levels and risk of coronary artery disease and graft
      failure following heart transplantation.
AB  - CONTEXT: Previous studies have yielded conflicting data regarding whether a
      relationship exists between elevated cardiac troponin levels and acute allograft
      rejection in patients who have received heart transplants. OBJECTIVE: To
      determine whether cardiac troponin I levels after heart transplantation were
      associated with a procoagulant microvasculature and long-term allograft outcome.
      DESIGN: Prospective cohort study with a mean (SE) follow-up of 45.1 (2.5) months.
      Serum troponin I levels were measured 9.9 (0.2) times per patient during the
      first 12 months after heart transplantation. SETTING: Heart transplant center in
      the United States. PATIENTS: A total of 110 consecutive patients who received a
      heart transplant between 1989 and 1997 and survived at least 1 year after
      transplantation. MAIN OUTCOME MEASURES: Histological and immunohistochemical
      biopsy findings, development of coronary artery disease (CAD), and graft failure
      in patients with vs without elevated serum cardiac troponin I levels. RESULTS:
      All recipients had elevated troponin I levels during the first month after
      transplantation. Troponin I levels remained persistently elevated during the
      first 12 months in 56 patients (51%) and became undetectable in 54 patients
      (49%). Persistently elevated troponin I levels were associated with increasing
      fibrin deposits in microvasculature and cardiomyocytes (P<.001). Patients with
      persistently elevated levels of troponin I had significantly increased risk for
      subsequent development of CAD (odds ratio [OR], 4. 3; 95% confidence interval
      [CI], 1.8-10.1; P<.001) and graft failure (OR, 3.4; 95% CI, 1.2-9.7; P =.02), and
      also developed more severe CAD (OR, 4.2; 95% CI, 1.9-9.3; P<.001) and showed more
      disease progression (OR, 3.7; 95% CI, 1.3-10.4; P =.009). CONCLUSION: In this
      study, elevated cardiac troponin I levels, which are considered to be a
      noninvasive surrogate marker of a procoagulant microvasculature, identified a
      subgroup of patients with high risk for developing CAD and graft failure after
      cardiac transplantation. JAMA. 2000;284:457-464

PMID- 10904510
TI  - Effect of treating isolated systolic hypertension on the risk of developing
      various types and subtypes of stroke: the Systolic Hypertension in the Elderly
      Program (SHEP).
AB  - CONTEXT: The Systolic Hypertension in the Elderly Program (SHEP) demonstrated
      that treating isolated systolic hypertension in older patients decreased
      incidence of total stroke, but whether all types of stroke were reduced was not
      evaluated. OBJECTIVE: To investigate antihypertensive drug treatment effects on
      incidence of stroke by type and subtype, timing of strokes, case-fatality rates,
      stroke residual effects, and relationship of attained systolic blood pressure to
      stroke incidence. DESIGN: The SHEP study, a randomized, double-blind, placebo
      controlled trial began March 1, 1985, and had an average follow-up of 4.5 years.
      SETTING AND PARTICIPANTS: A total of 4736 men and women aged 60 years or older
      with isolated systolic hypertension at 16 clinical centers in the United States.
      INTERVENTIONS: Patients were randomly assigned to receive treatment with 12.5
      mg/d of chlorthalidone (step 1); either 25 mg/d of atenolol or 0.05 mg/d of
      reserpine (step 2) could be added (n = 2365); or placebo (n = 2371). MAIN OUTCOME
      MEASURES: Occurrence, type and subtype, and timing of first strokes and stroke
      fatalities; and change in stroke incidence for participants (whether in active
      treatment or placebo groups) reaching study-specific systolic blood pressure goal
      (decrease of at least 20 mm Hg from baseline to below 160 mm Hg) compared with
      participants not reaching goal. RESULTS: A total of 85 and 132 participants in
      the active treatment and placebo groups, respectively, had ischemic strokes
      (adjusted relative risk [RR], 0.63; 95% confidence interval [CI], 0.48-0.82); 9
      and 19 had hemorrhagic strokes (adjusted RR, 0.46; 95% CI, 0.21-1.02); and 9 and
      8 had strokes of unknown type (adjusted RR, 1.05; 95% CI, 0.40-2. 73),
      respectively. Four subtypes of ischemic stroke were observed in active treatment
      and placebo group participants, respectively, as follows: for lacunar, n = 23 and
      n = 43 (adjusted RR, 0.53; 95% CI, 0.32-0.88); for embolic, n = 9 and n = 16
      (adjusted RR, 0.56; 95% CI, 0.25-1.27); for atherosclerotic, n = 13 and n = 13
      (adjusted RR, 0. 99; 95% CI, 0.46-2.15); and for unknown subtype, n = 40 and n =
      60 (adjusted RR, 0.64; 95% CI, 0.43-0.96). Treatment effect was observed within 1
      year for hemorrhagic strokes but was not seen until the second year for ischemic
      strokes. Stroke incidence significantly decreased in participants attaining study
      specific systolic blood pressure goals. CONCLUSIONS: In this study,
      antihypertensive drug treatment reduced the incidence of both hemorrhagic and
      ischemic (including lacunar) strokes. Reduction in stroke incidence occurred when
      specific systolic blood pressure goals were attained. JAMA. 2000;284:465-471

PMID- 10904511
TI  - Metformin in the treatment of HIV lipodystrophy syndrome: A randomized controlled
      trial.
AB  - CONTEXT: A syndrome of lipodystrophy, characterized by fat redistribution and
      insulin resistance, has been estimated to affect the majority of human
      immunodeficiency virus (HIV)-infected individuals who are treated with
      combination antiretroviral therapy. There are no proven therapies for the
      metabolic disturbances associated with HIV lipodystrophy syndrome. OBJECTIVE: To
      determine the safety and efficacy of metformin therapy in HIV-infected patients
      with fat redistribution and abnormal glucose homeostasis. DESIGN AND SETTING:
      Randomized, double-blind, placebo-controlled pilot study conducted in a
      university hospital between December 1998 and January 2000. PATIENTS: Twenty-six
      HIV-infected, nondiabetic patients with fat redistribution and abnormal oral
      glucose tolerance test (OGTT) results, hyperinsulinemia, or both. INTERVENTIONS:
      Patients were randomly assigned to receive metformin, 500 mg twice daily (n =
      14), or identical placebo (n = 12), for 3 months. MAIN OUTCOME MEASURES: Insulin
      area under the curve (AUC), calculated 120 minutes following a 75-g OGTT at
      baseline vs at 3-month follow-up and compared between treatment groups. RESULTS:
      Patients treated with metformin demonstrated significant reductions in mean (SEM)
      insulin AUC 120 minutes after OGTT (-2930 [912] vs -414 [432] microIU/mL [-20349
      6334 vs -2875 3000 pmol/L]; P =.01), weight (-1.3 [0.6] vs 1.1 [0.4] kg; P
      =.005), and diastolic blood pressure (-5 [4] vs 5 [2] mm Hg; P =.009) vs
      controls, respectively. Metformin therapy was associated with a decrease in
      visceral abdominal fat (VAT; -1115 [819] vs 1191 [699] mm(2); P =.08) and a
      proportional reduction in subcutaneous abdominal fat (SAT); the VAT-SAT ratio was
      unchanged in metformin-treated vs placebo-treated patients. No increase in
      lactate or liver transaminase levels was observed with metformin treatment. Mild
      diarrhea was the most common adverse effect of metformin. No patient discontinued
      therapy because of adverse effects. CONCLUSIONS: This study suggests that a
      relatively low dosage of metformin reduces insulin resistance and related
      cardiovascular risk parameters in HIV-infected patients with lipodystrophy. JAMA.
      2000;284:472-477

PMID- 10904512
TI  - Users' guides to the medical literature: XXIII. Qualitative research in health
      care B. What are the results and how do they help me care for my patients?
      Evidence-Based Medicine Working Group.
AB  - The second part of this 2-part series on how to interpret qualitative research
      addresses, "what are the results," and, "how do they help me care for my
      patients?" Qualitative analysis is a process of summarizing and interpreting data
      to develop theoretical insights that describe and explain social phenomena such
      as interactions, experiences, roles, perspectives, symbols, and organizations.
      Key results are often illustrated with excerpts from interview transcripts, field
      notes, or documents. The results of a qualitative research report are best
      understood as an empirically based contribution to ongoing dialogue and
      exploration. Empirically based theory evolves from a process of exploration,
      discovery, analysis, and synthesis. Each concept should be defined carefully in a
      way that is meaningful to the reader. Concepts should be adequately developed and
      illustrated when theoretical conclusions are drawn. Arguments should be explained
      and justified. The qualitative research report ideally should address how the
      findings relate to other theories in the field. The qualitative study can provide
      a useful road map for understanding and navigating similar social settings
      interactions, or relationships. JAMA. 2000;284:478-482

PMID- 10904513
TI  - Is US health really the best in the world?

PMID- 10904514
TI  - Sex and cyberspace-virtual networks leading to high-risk sex.

PMID- 10904515
TI  - Univentricular atrioventricular connection. Review of the current therapeutical
      possibilities

PMID- 10904516
TI  - Permanent and temporary pacemaker implantation after orthotopic heart
      transplantation
AB  - PURPOSE: To determine the indication for and incidence and evolution of temporary
      and permanent pacemaker implantation in cardiac transplant recipients. METHODS: A
      retrospective review of 114 patients who underwent orthotopic heart
      transplantation InCor (Heart Institute USP BR) between March 1985 and May 1993.
      We studied the incidence of and indication for temporary pacing, the relationship
      between pacing and rejection, the need for pemanent pacing and the clinical
      follow-up. RESULTS: Fourteen of 114 (12%) heart transplant recipients required
      temporary pacing and 4 of 114 (3.5%) patients required permanent pacing. The
      indication for temporary pacing was sinus node dysfunction in 11 patients (78.5%)
      and atrioventricular (AV) block in 3 patients (21.4%). The indication for
      permanent pacemaker implantation was sinus node dysfunction in 3 patients (75%)
      and atrioventricular (AV) block in 1 patient (25%). We observed rejection in 3
      patients (21.4%) who required temporary pacing and in 2 patients (50%) who
      required permanent pacing. The previous use of amiodarone was observed in 10
      patients (71.4%) with temporary pacing. Seven of the 14 patients (50%) died
      during follow-up. CONCLUSION: Sinus node dysfunction was the principal indication
      for temporary and permanent pacemaker implantation in cardiac transplant
      recipients. The need for pacing was related to worse prognosis after cardiac
      transplantation.

PMID- 10904517
TI  - Chest pain in the emergency room. Importance of a systematic approach
AB  - OBJECTIVE: To evaluate the efficiency of a systematic diagnostic approach in
      patients with chest pain in the emergency room in relation to the diagnosis of
      acute coronary syndrome (ACS) and the rate of hospitalization in high-cost units.
      METHODS: One thousand and three consecutive patients with chest pain were
      screened according to a pre-established process of diagnostic investigation based
      on the pre-test probability of ACS determinate by chest pain type and ECG
      changes. RESULTS: Of the 1003 patients, 224 were immediately discharged home
      because of no suspicion of ACS (route 5) and 119 were immediately transferred to
      the coronary care united because of ST elevation or left bundle-branch block
      (LBBB) (route 1) (74% of these had a final diagnosis of acute myocardial
      infarction [AMI]). Of the 660 patients that remained in the emergency room under
      observation, 77 (12%) had AMI without ST segment elevation and 202 (31%) had
      unstable angina (UA). In route 2 (high probability of ACS) 17% of patients had
      AMI and 43% had UA, whereas in route 3 (low probability) 2% had AMI and 7% had
      UA. The admission ECG has been confirmed as a poor sensitivity test for the
      diagnosis of AMI (49%), with a positive predictive value considered only
      satisfactory (79%). CONCLUSION: A systematic diagnostic strategy, as used in this
      study, is essential in managing patients with chest pain in the emergency room in
      order to obtain high diagnostic accuracy, lower cost, and optimization of the use
      of coronary care unit beds.

PMID- 10904518
TI  - The results of the campaign for evaluating sphygmomanometers accuracy and their
      physical conditions
AB  - OBJECTIVE: To evaluate the sphygmomanometers calibration accuracy and the
      physical conditions of the cuff-bladder, bulb, pump, and valve. METHODS: Sixty
      hundred and forty five aneroid sphygmomanometers were evaluated, 521 used in
      private practice and 124 used in hospitals. Aneroid manometers were tested
      against a properly calibrated mercury manometer and were considered calibrated
      when the error was < or = 3 mm Hg. The physical conditions of the cuffs-bladder,
      bulb, pump, and valve were also evaluated. RESULTS: Of the aneroid
      sphygmomanometers tested, 51% of those used in private practice and 56% of those
      used in hospitals were found to be not accurately calibrated. Of these, the
      magnitude of inaccuracy ranged from 4 to 8 mm Hg in 70% and 51% of the devices,
      respectively. The problems found in the cuffs--bladders, bulbs, pumps, and valves
      of the private practice and hospital devices were bladder damage (34% vs. 21%,
      respectively), holes/leaks in the bulbs (22% vs. 4%, respectively), and rubber
      aging (15% vs. 12%, respectively). Of the devices tested, 72% revealed at least
      one problem interfering with blood pressure measurement accuracy. CONCLUSION:
      Most of the manometers evaluated, whether used in private practice or in
      hospitals, were found to be inaccurate and unreliable, and their use may
      jeopardize the diagnosis and treatment of arterial hypertension.

PMID- 10904519
TI  - Acute myocardial infarction in the Brazilian State of Sao Paulo. In-hospital
      deaths from 1979 to 1996 and hospital fatality from 1984 to 1998 in the public
      health system
AB  - OBJECTIVE: To determine the following parameters in the Brazilian State of Sao
      Paulo: 1) the percentage of deaths due to acute myocardial infarction (AMI)
      occurring in hospitals; 2) the percentage of deaths due to AMI occurring in
      public health system hospitals as compared with all in-hospital deaths due to AMI
      between 1979 and 1996; 3) the fatality due to AMI in public health system
      hospitals from 1984 to 1998. METHODS: Data were available on the Datasus Web site
      (the health information agency of the Brazilian Department of Health) that
      provided the following: a) number of deaths resulting from AMI in hospitals; b)
      number of deaths resulting from AMI in public health system hospitals; c) number
      of hospital admissions due to AMI in public health system hospitals. RESULTS: The
      percentage of in-hospital deaths due to AMI increased from 54.9 in 1979 to 68.6
      in 1996. The percentage contribution of the public health system to total number
      of deaths due to AMI occurring in hospitals decreased from 22.9 in 1984 to 13.7
      in 1996; fatality due to AMI occurring in public health system hospitals had an
      irregular evolution from 1984 to 1992 and showed a slight trend for increased
      frequency from 1993 to 1998. CONCLUSION: The percentage of in-hospital deaths due
      to AMI has been increasing. Deaths resulting from AMI in public health system
      hospitals have decreased when compared with the total number of deaths due to AMI
      in all hospitals. Fatality due to AMI in public health system hospitals did not
      decrease from 1992 to 1998.

PMID- 10904520
TI  - Constrictive pericarditis in a 19-month-old child
AB  - We report a case of chronic nonspecific constrictive pericarditis with myocardial
      involvement in a 19-month-old infant. The patient underwent total pericardiectomy
      and had irreversible hemodynamic instability. Constrictive pericarditis is rare
      in childhood. It may follow several processes, most frequently an infectious
      disease. The natural course of the disease consists of progressive myocardial
      dysfunction with atrioventricular valvular involvement. When diagnosis is
      established early in the course of the disease and treatment started immediately,
      the evolution is favorable in most instances.

PMID- 10904521
TI  - Lupus carditis

PMID- 10904523
TI  - The lung of the common toad, Bufo arenarum (Anura: Bufonidae). A light and
      electron microscopy study.
AB  - The present study describes the lung morphology of the common toad, Bufo
      arenarum, as observed by light and electron microscopy. The lung wall consists of
      four layers: mesothelium, dense connective tissue with thin elastic fibers, loose
      connective tissue containing smooth muscle fibers and an internal respiratory
      epithelium. The lung presents three types of folds defined by their epithelia.
      First order folds are coated by ciliated epithelium containing numerous goblet
      cells. Second order folds present the same type of epithelium but devoid of
      goblet cells, while third order folds are only lined by respiratory epithelium.
      The respiratory surface of the lung is lined by a single cell type, the
      pneumocyte, which presents characteristics of both type I and type II alveolar
      cells of higher vertebrates. The pneumocytes are prismatic in shape and possess
      attenuated cytoplasmatic processes which spread over the pulmonary capillaries to
      form the outer layer of the air-blood barrier. These cells present microvilli in
      the apical extreme and contain different types of cytoplasmic bodies: electron
      dense, multivesicular and lamellar.

PMID- 10904524
TI  - Nuclear maturation inhibitors in Bufo arenarum oocytes.
AB  - In Bufo arenarum, as in other amphibian species, nuclear maturation-
      characterized by germinal vesicle breakdown (GVBD) and meiosis resumption--is
      induced by progesterone. Seasonal variations in the sensitivity to progesterone
      were observed in Bufo arenarum oocytes. The gonadotropin FSH and drugs such as
      dbcAMP and xanthine did not affect nuclear maturation per se, although they acted
      as negative modulators of progesterone-induced nuclear maturation. Similar
      results to FSH in nuclear maturation were obtained with 17 beta-estradiol.

PMID- 10904525
TI  - Coculture of chicken thrombocytes and monocytes: morphological changes and lectin
      binding.
AB  - Chicken leukocytes were separated from blood on a Percoll cushion following
      adherence on coverslips, resulting in a coculture of thrombocytes and monocytes.
      This system was characterized by light microscopy, scanning and transmission
      electron microscopy, by lectin binding and actin localization in thrombocytes.
      During the first 24 hours nuclear condensation, cytoplasmic shrinkage, detachment
      and death of thrombocytes were observed. In contrast, monocytes gradually
      increased their spreading capacity, specially after thrombocyte detachment from
      the coverslips. During culture, a large number of fucose and beta-galactose
      residues were expressed on the surface of thrombocytes, revealed by the lectins
      Ulex europaeus I and Arachis hypogaea, respectively. Labeling of the monocyte
      surface with several lectins also increased with the cultivation time.
      Thrombocytes showed the formation of a net with actin involvement.

PMID- 10904526
TI  - Involvement of blood serum in amphibian fertilization.
AB  - A proteolytic enzyme secreted by the first portion of amphibian oviduct, pars
      recta, called oviductin in Xenopus laevis, causes ultrastructural alterations on
      the extracellular matrix of coelomic eggs, turning them susceptible to
      fertilization. Although great advances have been made in the field of
      reproduction, the molecular mechanisms responsible for the fusion between the egg
      and the sperm are yet to be understood. We have recently demonstrated the
      presence of proteins from pars recta fluid in blood serum and extracellular
      matrix of coelomic eggs in Bufo arenarum. Here we show, using immunofluorescence
      procedures, that blood serum components are present in the extracellular matrix
      of coelomic and pars recta fluid-conditioned eggs in Bufo arenarum. Furthermore,
      by assessing the neutralizing effect on the conditioning activity of pars recta
      fluid on coelomic eggs we found that antibodies against pars recta secretions and
      blood serum inhibited the effect of sperm-lysin on the vitelline envelope of
      conditioned oocytes and impaired fertilization by sperm. Thus, serum proteins
      appear to be implicated in the molecular events that lead to amphibian
      fertilization.

PMID- 10904527
TI  - Distribution of GABA in the golden hamster retina. An immunocytochemical study.
AB  - Distribution of the inhibitory neurotransmitter GABA was studied in the golden
      hamster retina using immunocytochemistry at cellular and subcellular levels. GABA
      immunoreactivity was observed in somata of amacrine, displaced amacrine and
      horizontal cells. GABA immunoreactive fibers were abundant in the inner plexiform
      layer. Ultrastructural analysis exhibited dense GABA-immunoreactive deposits in
      amacrine cell somata, processes and terminals. Immunolabelling was also observed
      in the cytoplasm of horizontal or interplexiform cells and displaced amacrine
      cells. In every case DAB deposits were observed in the cytosolic compartment,
      attached to the inner surface of cell membranes and to outer mitochondrial
      membranes. Immunolabeled terminals predominated in the inner plexiform layer and
      immunoprecipitates were also observed attached to the outer face of vesicle
      membranes as well as completely filling synaptic vesicles. Both clear and dense
      core vesicles were observed. The present results are similar to those obtained in
      other mammalian species showing GABA immunoreactivity in amacrine, displaced
      amacrine and horizontal cells.

PMID- 10904528
TI  - Neuropeptide tyrosine-like immunoreactivity (NPY-LI) in ganglion neurons in the
      adrenal gland of the flat snake (Waglerophis merremii).
AB  - In previous morphological and histochemical studies on the adrenal gland of the
      flat snake, no data demonstrating the existence of ganglion neurons has been
      reported. The aim of this paper was therefore to establish the presence of
      ganglion neurons in the adrenal gland of the flat snake Waglerophis merremii and,
      further to study their chemical phenotype using immunohistochemistry. Our results
      showed the presence of cells which were immunolabelled with the neuronal marker
      neurofilament 10 and were thus identified as large ganglion neurons. These cells
      were localized in the dorsal ribbon of the gland, suggesting a noradrenergic
      phenotype, exhibited long processes with a longitudinal direction and co
      expressed neuropeptide tyrosine- (NPY) and tyrosine hydroxylase-like
      immunoreactivities (-LI). In addition, NPY-immunoreactive (-IR) fibers were
      recognized with a wide distribution throughout the gland whereas vasoactive
      intestinal polypeptide (VIP)-IR fibers were only observed between clusters of
      cortical and adrenergic chromaffin cells. No cells containing VIP-LI were
      detected within the gland. Based on their histochemical phenotype, ganglion cells
      containing NPY and TH could correspond to ganglion neurons type I of the rat. The
      possible absence of type II ganglion neurons in the adrenal gland of the snake is
      discussed.

PMID- 10904529
TI  - Cytochemical localization of phosphatases in the germ- and Sertoli cells of
      Odontophrynus cultripes (Amphibia, Anura, Leptodactylidae).
AB  - Ultrastructural cytochemical techniques were used for the localization of
      phosphatases in spermatid and spermatozoon, as well as in Sertoli cells of
      Odontophrynus cultripes (Amphibia, Anura, Leptodactylidae). Acid phosphatase was
      found in the acrosome. Thiamine pyrophosphatase was observed in the Golgi
      cisternae and in the tail spermatozoon surface. Glucose-6-phosphatase was located
      in the membrane complex of the acrosomal region. Already, in the Sertoli cells
      acid phosphatase was located in the lysosomes and glucose-6-phosphatase was
      observed in association with the endoplasmic reticulum and Golgi complex. These
      observations support the idea that various phosphatases may play some role in
      spermatid differentiation and in the interactions germ cells--Sertoli cells
      during spermiogenesis process.

PMID- 10904531
TI  - Serotonergic ependymal fibres in rat and monkey: light and electron microscopic
      immunocytochemical study.
AB  - The distribution of serotonin (5HT) immunoreactive fibres in the ependymal
      epithelium of aqueductus cerebri in adult rat and monkey was studied by means of
      immunocytochemical methods using specific antibodies against 5HT. Light
      microscopic examination of immunostained coronal sections of mesencephalon
      showed, in tryptophan and pargylin pretreated animals, abundant serotonergic
      fibres distributed along the ependymal cells of the aqueduct, forming
      supraependymal and subependymal plexi. Serotonin fibres lying either
      supraependymally or ending freely in the aqueduct lumen contributed to the
      formation of a rich 5HT containing network on the ependymal surface. Electron
      microscope images showed dense 5HT-immunoreactive (5HT-IR) profiles with
      ultrastructural characteristics of axon terminals ending on the ependymal cells.
      Dense diaminobenzidine (DAB) deposits were found in the axoplasm, on outer
      mitochondrial surface and in vesicles. No synaptic contacts were observed between
      5HT-IR terminals and ependymal cells. Unstained microvilli and cilia were also
      observed in the aqueduct lumen. Serotonin immunoreactivity disappeared from
      ependymal fibres in animals treated with parachlorophenylalanine, an inhibitor of
      5HT synthesis. 5HT containing fibres described in this paper may be the source of
      5HT and its metabolite 5-hydroxyindoleacetic acid (5HIAA) found in cerebrospinal
      fluid (CSF) and of clinical relevance in some psychiatric conditions such as
      depression, suicidal attempts, etc.

PMID- 10904530
TI  - Hormone uptake and morphological changes in cultured pituicytes exposed to
      oxytocin and vasopressin.
AB  - Enzymatically dispersed cells, isolated from adult female rat neural lobes, were
      cultured for 7 days. Routine cultures showed pituicytes with compact, sometimes
      ovoid, cell bodies. The cytoplasmic processes of these cells exhibited several
      varicosities and made contact with neighboring cells forming networks. The
      cultured pituicytes were immunocytochemically characterized using antisera to
      glial fibrillary acidic protein and to S-100. Most pituicytes, when exposed
      during culture to oxytocin (OXY) and vasopressin (VP; 1 microM each), were devoid
      of their characteristic processes. Immunocytochemical staining for OXY or VP
      revealed that the pituicytes were capable of incorporating these hormones during
      culture. In cultures without added hormones, no significant staining reaction for
      OXY or VP could be detected. The lack of projections in pituicytes exposed to the
      hormones during culture is in agreement with the morphological changes observed
      by other authors in situ after acute hormone release. The uptake of OXY and VP
      may be indicative for a regulatory mechanism, by which the pituicytes control the
      amount of hormones present in the intercellular space.

PMID- 10904532
TI  - The brain of the armadillo Dasypus hybridus. A general view of its most salient
      features.
AB  - The most salient neuroanatomical features of the brain of the seven banded
      armadillo Dasypus hybridus are described. The microscopic characteristics were
      studied by serial transverse and sagittal paraffin sections, stained with Nissl
      and Kluver-Barrera technique. This analysis comprises the telencephalon,
      diencephalon and mesencephalon. The most outstanding features of this brain are:
      1) Great development of rhinencephalic structures (olfactory bulbs, olfactory
      tubercles, anterior commissure and pyriform cortex). 2) The relative size of the
      induseum griseum strongly suggests that this animal would be useful for a variety
      of studies on this structure. 3) The high position of the rhinal fissure on the
      lateral hemispheric wall determines the smallness of neocortex. Therefore, this
      armadillo is also useful for decortication studies. 4) Absence of a distinct
      pineal organ. 5) Conspicuous subfornical and subcommissural organs. 6) Absence of
      a distinct intermediate lobe in the hypophysis.

PMID- 10904533
TI  - Effect of dexamethasone on nitric oxide (NO.) production by cultured astrocytes.
AB  - Glial cell-derived nitric oxide (NO.) and its regulation has significant
      implications for central nervous system pathophysiology. The aim of the present
      study was to determine the production of NO. by cultured rat astrocytes and
      peritoneal macrophages, and its regulation by glucocorticoids. Results
      corroborate the presence of both constitutive and induced NO. synthase (cNOS and
      iNOS) in astrocytes, while macrophages express only the inducible isoform.
      Dexamethasone was able to decrease NO. synthesis produced by induction of iNOS in
      macrophage and astrocyte phagocytosis, but not the NO. produced by the cNOS
      spontaneously expressed in cultured astrocytes.

PMID- 10904534
TI  - Comparative analysis of three methods to assess viability of mammalian cells in
      culture.
AB  - Release of lactate dehydrogenase (LDH) from the cytoplasmic compartment, trypan
      blue exclusion and methylthiazole tetrazolium (MTT) colorimetric assays were
      compared with regard to their sensitivity in detecting damage of human cultured
      epithelial cells induced by sodium fluoride or puromycin. LDH assay did not
      detect any difference between controls and cells treated with either of the two
      drugs. Cell monolayers treated with 0.3% sodium fluoride or 10(-2) M puromycin
      presented higher percentages of cells that took up the trypan blue dye than
      controls but monolayers treated with lower drug concentrations did not differ
      from controls. Viability measured by MTT assay was the most sensitive assay,
      detecting a dose-dependent impairment of cell function after treatment with the
      two drugs. Moreover, MTT offered major advantages in speed, simplicity and
      precise quantitation over the other viability assays.

PMID- 10904535
TI  - Origin and evolution of the sex chromosomes in birds.
AB  - A scheme is proposed to explain the process of sex chromosome differentiation in
      the class Aves. It is based on the restriction of recombination in an ancestral
      homomorphic ZW pair and the subsequent degeneration of the non-recombining region
      of the W chromosome leading to the highly heteromorphic sex chromosomes of
      carinate birds. The model presented here and Ohno's model of sex chromosome
      differentiation in Ophidia are the only integral models of sex chromosome
      evolution based on cytological evidences. The co-existence among living birds of
      mostly homomorphic (Ratites) and highly heteromorphic ZW pairs (carinates)
      provides a unique ground to study the mechanisms of sex chromosome
      differentiation in vertebrates.

PMID- 10904536
TI  - Fibronectin substrate induces shortening of in vitro neural crest cell mitotic
      cycle.
AB  - Neural crest cells (NCC) segregate from neural folds, swim through extracellular
      matrix, and differentiate in several cell types. During in vivo and in vitro
      dispersion, NCC display a substantial proliferative rate. Here, we have evaluated
      this biological behavior under the influence of different substrates. NCC exhibit
      the highest proliferative activity on fibronectin substrate, with shortening of
      the G1 period. This fact is reverted by specific antibody pre-treatment of the
      substrate. Taking into account that NCC migrate along narrow and restricted
      pathways rich in essential fibronectin, with high proliferative rates, these
      results indicate that the fibronectin pathway contributes to increase the cell
      number, leading to a high population pressure that could participate in the early
      dispersion of NCC.

PMID- 10904537
TI  - Study of evaluation criteria used for in vitro bovine oocyte selection and
      maturation.
AB  - Production of bovine preimplantation embryos in vitro requires beneficial
      maturation conditions and high quality oocytes at the germinal vesicle stage. The
      current classification of oocytes is based on character of the cumulus cell
      investment around the oocyte. We wished to study the nuclear stage of immature
      oocytes selected for in vitro maturation according to cumulus cell character and,
      in the other hand, to compare the relationship among 3 parameters utilized to
      evaluate in vitro maturation of bovine oocytes (degree of cumulus expansion,
      meiotic maturation rate and in vitro fertilization rate) when fetal calf serum,
      steer serum and bovine follicular fluid supplementation were used. Ovaries were
      collected at an abattoir and the oocytes harvested. As regards selection
      criteria, immature oocytes were classified as Class A, B, C and D according to
      the character of the cumulus cells. A high percentage of Class A oocytes (87.7%)
      were in the germinal vesicle stage with respect to the other classes (p < 0.05).
      Significant differences were found in the meiotic maturation rate in Class A
      oocytes (76.5%) versus those of the other classes (p < 0.05). The meiotic
      maturation rate diminished to 47.5% when Class A oocytes were denuded and then
      matured in vitro (p < 0.05). As regards maturation criteria, there was no cumulus
      expansion when oocytes were matured in TCM-199 without supplementation, partial
      expansion with the addition of fetal calf serum and full expansion when
      supplemented with steer serum or bovine follicular fluid. No significant
      differences were found in the meiotic maturation rate for the various treatments.
      In vitro fertilization rate was significantly lower in media without
      supplementation versus supplemented media (p < 0.05), but no significant
      differences were found between the supplemented media inter se. There is no
      direct relationship between the three studied parameters to evaluate in vitro
      maturation. Class A oocytes are the most likely to mature in vitro as they not
      only have a close association with their surrounding cumulus cells, but are also
      very numerous in the germinal vesicle stage. The degree of cumulus expansion and
      the meiotic maturation rate have a relative importance in evaluating in vitro
      maturation, as oocyte maturation implies not only nuclear events but also at
      other cellular levels, as evaluated by in vitro fertilization.

PMID- 10904539
TI  - Microwave-enhanced of a method of silver impregnation applied in
      dermatohistopathology.
AB  - An experimental development based on the combination of microwaves action with
      one of the methods of silver staining by Del Rio Hortega is presented. Materials
      from normal and pathological tissues were studied. The stuff were fixed in 10%
      formalin and received a paraffined embedding. The impregnation was made with
      ammoniacal silver carbonate in a domestic microwave oven during twelve seconds at
      375 w. As a result of this, a time shortage of the technique, the high degree of
      definition of the nuclear, cytoplasmatic and extracellular matrix (collagenus
      fibbers with an unsteady reticular representation) details and the easy
      visualization of mitosis was observed. Also, omitting the reduction, they were
      clearly evidenced the argirophilics granules (melanin pigment).

PMID- 10904538
TI  - Morphofunctional disturbances of human sperm after incubation with
      organophosphorate pesticides.
AB  - The organophosphorate pesticides are highly toxic for insects and mammals, but
      their effects in the male reproductive tract are scarcely known. Many alterations
      induced by organophosphorate pesticides have been described, such as: cytogenetic
      alterations in germinal cells, oligozoospermia and teratozoospermia in the mouse.
      Parathion, the pesticide mostly utilized in Chilean agriculture, is rapidly
      metabolized to paraoxon, the active metabolite, in mammalian organisms. The
      purpose of this study is to evaluate the effect of Parathion and paraoxon on
      different morphological and functional parameters of the sperm. Human spermatozoa
      were incubated with Parathion and paraoxon at different concentrations (0.05,
      0.1, 0.2, 0.4 and 0.8 mM). Vitality (tripan blue and eosin tests), acrosome
      reaction (triple stain test), plasma membrane integrity (HOS-test), and chromatin
      stability (sodium thioglycolate test) were determined. The observations were done
      by optical microscopy at 1000x of magnification and three hundred sperms were
      evaluated for each treatment. The results indicated that Parathion and paraoxon
      increase the percent of sperm with acrosome reaction and also increase the
      percentage of sperm with chromatin decondensation in a dose-dependent manner. The
      vitality and plasma membrane integrity decrease significantly in a dose-dependent
      manner. The results suggest a direct action of Parathion and paraoxon on the
      different parameters studied. The morphofunctionality of sperm is altered
      significatively, suggesting that Parathion and paraoxon, thanks to their
      alkylating and electrophylic properties, could act on DNA and proteins
      respectively, to elicit these changes.

PMID- 10904540
TI  - Biogenesis of lysosomes by endocytic flow of plasma membrane.
AB  - The objective of this review is to examine the biogenesis of lysosomes during the
      endocytic flow of plasma membrane. Two models have been proposed to explain the
      formation of lysosomes by this process: the "maturational" and the "stationary"
      models. According to the former, pinocytotic vesicles fuse among themselves to
      yield endosomes, which in turn, transform first into multivesicular bodies (MVB)
      and then into mature lysosomes. Therefore, endosomes and lysosomes would be
      transient organelles. On the other hand, the "stationary" model proposes that the
      endocytic pathway is formed by functionally and physically distinct compartments.
      Cultured cells exposed to ammonium chloride (NH4Cl) and leupeptin after a pulse
      of cationic ferritin were recently used to freeze endosomes and lysosomes. NH4Cl
      produced a retention of cationic ferritin in endosomes, indicating that this
      agent interfered with the endosomal/lysosomal progression. Leupeptin did not
      affect this process. The number of lysosomes increased in cells treated with both
      lysosomotropic agents. Thus, NH4Cl affected the endosomal and lysosomal
      compartments, whereas leupeptin had a preferential effect on lysosomes. Mice
      mutants with defects of plasma membrane degradation, including a Tay-Sachs model,
      a Sandhoff disease model, as well as, mice with the inactivated prosaposin gene
      were used to analyze the biogenesis of lysosomes. Thin sections of mutant cells
      were examined under the electron microscope, and the analysis revealed a
      selective accumulation of MVBs and the disappearance of lysosomes, suggesting
      that the formation of MVBs is a required step in lysosomal maturation and that
      the intravesicular content of MVBs is necessary for the digestion of plasma
      membrane components. Taken together, these data indicate that endosomes and MVBs
      are preceding steps in lysosomal biogenesis and that endosomes, MVBs, and
      lysosomes are transient organelles.

PMID- 10904541
TI  - Effect of glandular kallikrein on distal bicarbonate transport. Role of
      basolateral Cl-/HCO3- exchanger and vacuolar H(+)-ATPase.
AB  - The luminal membrane of collecting duct cells, specially the intercalated cells,
      is normally exposed to active kallikrein. This is due to the specific
      localization of renal kallikrein in the connecting tubule cells. We have
      previously reported inhibition of distal bicarbonate secretion by renal
      kallikrein. The present study was performed to evaluate the participation of
      basolateral Cl-/HCO3- exchanger and luminal H(+)-ATPase activity of cortical
      collecting duct segments (CCD) in the mechanism involved in the inhibition of
      bicarbonate secretion induced by the enzyme. The effect of orthograde injections
      of 1 microgram/ml (250 U/6.3 mg) pig pancreatic kallikrein, in the absence and
      presence of 1 mM DIDS (stilbene-disulfonic acid) in the renal tubule system, was
      evaluated. Urine fractions were collected after two-minutes stop-flow. Changes in
      the urine fraction (Fr) related to those in free-flow urine samples (Ff) were
      related to the respective polyfructosan (Inutest) ratio. Renal kallikrein
      activity (Fr:Ff kallikrein/Fr:Ff polyfructosan) increased significantly in the
      first 120 microliters urine fraction collected after glandular 1 microgram/ml
      kallikrein, P < 0.05, (first stop-flow) and after glandular 1 microgram/ml
      kallikrein plus 1 mM. DIDS P < 0.05 (second stop flow). Bicarbonate secretion
      rate (Fr:Ff HCO3-/Fr:Ff polyfructosan) of collecting ducts was significantly
      reduced in the first 120 microliters urine fraction collected, related to
      control, during the first and second stop-flow periods. No difference was shown
      in bicarbonate excretion between the first 120 microliters urine fractions
      collected after administration of glandular kallikrein and glandular kallikrein
      plus DIDS. To measure H(+)-ATPase activity, rat microdissected cortical collector
      tubules (CCD) were incubated in the presence of increasing glandular kallikrein
      doses (A: 93, B: 187 and C: 375 mU/200 microL) in the presence of ouabain (4
      microM) and omeprazole (100 microM) to inhibit Na(+)-K(+)-ATPase and H(+)-K(+)
      ATPase, respectively. In CCD, bafilomycin-sensitive H(+)-ATPase activity
      (pmol/mm/min) after increasing kallikrein doses did not differ significantly from
      control. No difference related to control H(+)-ATPase activity was observed when
      microdissected CCD segments were incubated in the presence of an AT1 receptor
      antagonist (Losartan 10(-6) M) and glandular kallikrein (93 mU). On the contrary,
      angiotensin II (10(-8) M) significantly decreased H(+)-ATPase activity. The
      present study shows that neither basolateral Cl-/HCO3- exchanger nor H(+)-ATPase
      activity are involved in bicarbonate inhibition by glandular kallikrein at CCD.
      Involvement of luminal Cl-/HCO3- exchanger at beta intercalated cells in CCD may
      be suggested for the bicarbonate secretion inhibition induced by renal
      kallikrein.

PMID- 10904542
TI  - "Osmetrichia" in the grey brocket deer (Mazama gouazoubira).
AB  - Osmetrichia have been defined as hairs specialized in the storage of secretions
      used in olfactory communication between conspecifics (Muller-Schwarze, et al.
      1977). These authors found highly specialized osmetrichia in the tarsal gland
      tufts of black-tailed but not white-tailed deer. Chemical communication appears
      to be well developed in grey brocket deer: the bucks scent mark by rubbing their
      foreheads on bushes, and all deer urinate and defecate almost exclusively on dung
      heaps. Brocket deer also possess tarsal tufts. The purpose of this study was to
      examine hairs from several glandular areas in this species. Osmetrichia, similar
      to those found in black tailed deer, were found in tarsal tufts and in
      interdigital gland hairs; these hairs possessed open scales with deep pockets
      suitable for holding secretions, in comparison to the flat scales seen on control
      hairs. Hairs with different morphological characteristics (slightly open scales)
      were found over the frontal gland. Specialized hairs were not found in the tarsal
      tufts of one specimen of a related species, the red brocket deer (Mazama
      americana). The similarities in the hairs of grey brocket and black-tailed deer
      are remarkable in light of the ecological and behavioral differences between
      these two species.

PMID- 10904543
TI  - Cytoarchitectonic arrangement and intracortical circuits of hamster cerebellum. A
      study by means of confocal scanning laser microscopy.
AB  - The FM4-64, a member of the family of fluorescent dyes, has been applied to the
      cerebellar cortex to study its cytoarchitectonic arrangement and intracortical
      course of mossy and climbing fibers. Slabs of hamster cerebellum, 1-2 mm thick,
      were incubated in 10, 30 and 100 microM solutions of FM4-64 in 0.1 M sodium
      phosphate buffer and observed in a slow scan confocal laser scanning microscope.
      Cellular tomography of cerebellar cortex allowed us to follow the course of mossy
      and climbing fibers in the cerebellar white and gray substance. They exhibited
      high fluorescence signal at the level of myelin sheath. Mossy fibers were
      identified only in the granular layer by their typical rosette formations and
      dichotomous bifurcation pattern. Climbing fiber bundles were observed crossing
      the granular layer and giving off collateral branches in the granular and
      molecular layers in a crossing-over pattern. They ascend to the Purkinje cell
      layer in their way to the molecular layer. Cerebellar macroneurons (Golgi and
      Purkinje cells) and microneurons (granule, basket and stellate cells) showed
      optimal intracellular staining of cell soma, axonal and proximal dendritic
      processes. The montage of z-series of stacked optodigital sections allowed us to
      explore in depth the cytoarchitectonic arrangement, nerve and glial cell
      morphology, and the topographic relationship of intrinsic cerebellar neurons with
      the afferent mossy and climbing fibers.

PMID- 10904544
TI  - Ultrastructural study of fossil human tooth tissue.
AB  - The preservation of fossil human soft tooth tissue from extinct populations which
      inhabited the northeast of Argentina (fourteenth and fifteenth centuries) is
      described. Studies were performed using both Scanning Electron Microscopy (SEM)
      and Transmission Electron Microscopy (TEM). The preservation of the surface
      structure in Tomes fibrils and in odontoblastic processes was determined by SEM;
      whereas by TEM we could observe the dentin ducts occupied by acellular material,
      being the inner structure of the odontoblastic processes poorly preserved. It is
      suggested that such preservation is due to an "instantaneous phosphatization"
      occurring immediately after death as a result of the presence of calcium
      phosphate deposits.

PMID- 10904545
TI  - An ultrastructural study of spermiogenesis in three species of Physalaemus
      (Anura, Leptodactylidae).
AB  - Ultrastructural aspects of spermiogenesis and testicular spermatozoa of three
      anuran amphibians, Physalaemus biligonigerus, P. fuscomaculatus and P. gracilis,
      were investigated by electron microscopy. The nuclei, middle pieces and tails of
      the three species were similar. In all cases, the nuclei were elongated and the
      acrosome consisted of a cone-shaped cap. The connecting pieces located in the
      flagellum implantation zone had transverse striations. The tails had a 9 + 2
      axial filament pattern, a juxtaxonemal fiber and an undulating membrane. In
      contrast to other Leptodactylidae spermatozoa, no axial rod were observed in
      these Physalaemus species.

PMID- 10904546
TI  - Apoptosis is regulated by polyamines in the cell cycle of Chinese hamster ovary
      cells.
AB  - This paper deals with the relationship between the polyamine metabolism and
      apoptosis in the different phases of the cell cycle in a Chinese hamster ovary
      (CHO) cell line. Synchronously growing cells were obtained by the addition of 1.2
      mM hydroxyurea and the progression through the cell cycle was monitored by
      determining the incorporation of 3H-thymidine in the DNA. Ornithine decarboxylase
      (ODC) activity showed a peak in S phase, while intracellular putrescine and
      spermine contents increased constantly, reaching to a maximum level at G2 phase;
      spermidine content doubled during G2 and increased four times during M, compared
      to G1. The increment in the endogenous polyamine content was associated to a
      diminished uptake from the medium. The apoptotic index was higher in G2 phase,
      coinciding with the maximum level observed in putrescine content. The results
      support the idea that intracellular putrescine level is closely related to
      apoptosis.

PMID- 10904547
TI  - Thermodynamics of protein folding: a statistical mechanical study of a small all
      beta protein.
AB  - The thermodynamic properties of a 46-mer beta-barrel protein model are
      investigated using Langevin dynamics and the histogram analysis method. By
      obtaining the density of states distribution and using the methods of statistical
      mechanics, we are able to identify the thermodynamic transitions for this model
      protein and characterize the nature of these transitions. Consistent with an
      earlier study of this model, we find that the transition from a random coil state
      to a manifold of collapsed but nonnative states is a continuous transition, and
      the transition from the manifold of collapsed states to the native state is first
      order-like. However, our calculations indicate that the folding transition is
      only weakly first order. Most importantly, we are able to characterize the free
      energy surface of the protein model, as well as the processes of compaction and
      native structure formation, from a statistical point of view. We also examined
      the thermodynamic transition state. By combining the earlier kinetic analysis for
      the same protein model, we provide a more complete description of this model
      protein and propose possible further modifications of the model to improve its
      stability and foldability.

PMID- 10904548
TI  - Structure, dynamics, and topological orientation of the polyether, ionophore
      antibiotic monensin, in a micellar environment.
AB  - The structure and dynamics of the ionophoric antibiotic monensin in the presence
      of micelles have been determined. The conformation of monensin was derived from
      50 nuclear Overhauser enhancement (NOE) derived distance restraints and metric
      matrix based distance geometry calculations. The conformation was further refined
      with extensive NOE restrained molecular dynamics simulations carried out in a
      biphasic simulation cell. From the addition of doxylstearate and monitoring of
      the induced relaxation of the nmr signals, the relative topological orientation
      of the molecule within the micelle was ascertained. The results indicate two
      dihedral angles that act as hinge regions allowing the molecule to adopt a wide
      range of conformations. Considering the biological activity of monensin, i.e.,
      the capture and transport of cations across cell membranes, an open and closed
      form of monensin have been postulated. The identification of these hinge regions,
      which are only observed in the membrane-like environment of the detergent
      micelles, provides insight into the mechanism of action and can serve as targets
      for modification to alter the biological profile of monensin.

PMID- 10904549
TI  - Solvent effects on the conformation and far UV CD spectra of gramicidin.
AB  - Solvent effects on the far-uv CD spectra of the polypeptide gramicidin have been
      studied systematically in a series of alcohols of increasing chain length,
      ranging from methanol to dodecanol. The effects observed are of two types:
      primary, involving a change in the equilibrium mixture of conformers present, and
      secondary, involving a shift in the spectral peak positions as a function of
      solvent polarizability. To quantitate the primary effect, the ratio of the
      individual conformers present was estimated by deconvolution of the spectra into
      their component species. For short chain length alcohols, both parallel and
      antiparallel double helices are found in considerable abundance. As the solvent
      chain length is increased and its polarity is decreased, the left-handed
      antiparallel double helical species is favored. For all alcohols with chain
      lengths of four or more carbon atoms, the ratio of the conformers present remains
      relatively constant. To quantitatively examine the secondary effect, the
      magnitudes of the spectral shifts on the dominant conformer (species 3) have been
      correlated with the dielectric constants and refractive indices of the solvents,
      thereby indicating what underlying physical properties are responsible for these
      shifts. This work thus demonstrates that for gramicidin, a flexible polypeptide,
      the solvent effects on the CD spectra can be resolved into two types: changes due
      to the mixture of conformers present and shifts in the spectral characteristics.
      Both effects need to be considered when interpreting CD spectra in terms of
      secondary structure for this and other polypeptides in nonaqueous solutions.

PMID- 10904550
TI  - Derivation of nearest-neighbor properties from data on nucleic acid oligomers. I.
      Simple sets of independent sequences and the influence of absent nearest
      neighbors.
AB  - The constraints on combinations of nearest neighbors in nucleic acid sequences
      and the numbers of independent sequences needed to describe nearest-neighbor
      properties of oligomers and polymers are derived and summarized. It has been
      pointed out in previous work [D. M. Gray and I. Tinoco, Jr. (1970) Biopolymers,
      Vol. 9, pp. 223-244; R. F. Goldstein and A. S. Benight (1992) Biopolymers, Vol.
      32, pp. 1679-1693] that these constraints restrict the information available from
      measurements of properties of sequence combinations. The emphasis in this paper
      is on the properties of oligomer sequences that vary in length, where each
      nucleotide or base pair at the end of the sequence makes a significant
      contribution to the measured property by interacting with its boundary of fixed
      sequence or solvent. In such cases it is not be possible to determine values of
      properties of individual nearest neighbors, except for the like neighbors [e.g.,
      d(A-A), d(G-G), d(T-T), and d(C-C) nucleotide neighbors in single-stranded DNA or
      d(A-A)/d(T-T) and d(G-G)/d(C-C) base pair neighbors in double-stranded DNA],
      solely from measurements of properties of different sequences. Even values for
      properties of the like neighbors cannot be determined from such oligomeric
      sequences if the sequences are all of the same length. Nearest-neighbor
      properties of oligomer sequences that vary in length can be summarized in terms
      of the values for independent sets of sequences that are nearest neighbors and
      monomers all with boundaries of the fixed sequence or solvent. Straightforward
      combinations of the values for the independent sequences will give the values of
      the property for any dependent sequence, without explicit knowledge of the
      individual nearest-neighbor values. These considerations have important
      consequences for the derivation of widely used thermodynamic parameters, as
      discussed in the following paper.

PMID- 10904551
TI  - Derivation of nearest-neighbor properties from data on nucleic acid oligomers.
      II. Thermodynamic parameters of DNA.RNA hybrids and DNA duplexes.
AB  - Using nearest-neighbor models consisting of independent short sequence
      combinations of nearest neighbors (ISS models), values of thermodynamic
      parameters for sets of independent sequences are derived from published oligomer
      data for DNA.RNA hybrids [N. Sugimoto, S. Nakano, M. Katoh, A. Matsumura, H.
      Nakamuta, T. Ohmichi, M. Yoneyama, and M. Sasaki (1995) Biochemistry, Vol. 34,
      pp. 11211-11216] and dsDNA duplexes [J. SantaLucia, Jr., H. T. Allawi, and P. A.
      Seneviratne (1996) Biochemistry, Vol. 35, pp. 3555-3562]. The results are
      compared with those from models that assign values of thermodynamic parameters to
      individual nearest neighbors (INN models). Differences in the use of ISS and INN
      models are also illustrated in an appendix, which shows examples of analyses for
      values of a fictitious nearest-neighbor property. INN models that include an
      initiation parameter contain an implicit assumption that combinations of end
      neighbors have the same value of a property. It is found that combinations of end
      neighbors (e.g., base pairs neighboring solvent) in oligomers can have
      significant and different apparent values of thermodynamic properties, so that
      the assumption inherent in INN models is not always correct. Even though ISS
      models do not allow the assignment of values to individual nearest neighbors,
      except for the like neighbors [such as d(AA)/r(UU), etc., for hybrids and
      d(AA)/d(TT) and d(GG)/d(CC) for DNA duplexes], they do provide physically
      meaningful values for the like neighbors, for sequence combinations, and for
      specified combinations of end neighbors.

PMID- 10904552
TI  - Order-disorder conformational transition in succinoglycan: calorimetric
      measurements.
AB  - Differential scanning microcalorimetry was performed on succinoglycan samples
      from different sources in order to better understand the thermally induced order
      disorder conformational transition of the polysaccharide. The shape of
      thermograms, as well as the melting temperature, were related to the content or
      distribution of the succinate groups at least in salt-free solution. With
      increasing polysaccharide and/or salt concentration, the change in the shape of
      the thermogram was attributed to a progressive screening of the succinate
      contribution to the order-disorder conformational transition instead of a change
      in the transition mechanism. In the presence of salt, contrary to the rheological
      behavior, the calorimetric results were found to be independent of the thermal
      history of the samples. This suggests a very low enthalpic contribution of the
      interchain interactions present in succinoglycan solutions. Possible
      contributions that could explain some discrepancies with results already
      published in the literature are discussed.

PMID- 10904553
TI  - Spin-labeled extracellular loop from a seven-transmembrane helix receptor:
      studies in solution and interaction with model membranes.
AB  - A spin-labeled pentadecapeptide was synthesized containing 2,2,6,6
      tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid (TOAC) as the N-terminal
      amino acid and residues 253-266 (EYWSTFGNLHHISL) of the mass oncogene receptor, a
      membrane-bound protein from the G-protein coupled receptors family. According to
      predictions, this protein folds into seven transmembrane helices connected by
      three extra- and three intracellular loops, and the peptide encompasses part of
      the third extracellular loop and part of the seventh helix. Electron paramagnetic
      resonance (EPR) spectra of the spin-labeled peptide (TOAC-14) were obtained in
      aqueous solution as a function of pH and temperature, in a secondary structure
      inducing solvent [trifluoroethanol (TFE)], and in the presence of detergent
      micelles and phospholipid bilayers. The charged and uncharged amino groups of
      TOAC and TOAC-14 yielded spectra with different isotropic hyperfine splittings
      (aN). The slow exchange between protonated and unprotonated forms in the EPR time
      scale gave rise to composite spectra weighted by the Henderson-Hasselbalch
      equation. Plots of aN vs pH allowed the determination of the amino group pK
      values (8.4 and 4.5, for TOAC and TOAC-14, respectively). A small change in aN
      centered at pH 6.5 was ascribed to the titration of the histidines. Values of
      calculated rotational correlation times were indicative of a pH-induced
      conformational change. A conformational change was also observed in TFE. TOAC-14
      bound to micelles irrespective of peptide and detergent head group charge. In
      contrast, the peptide bound to phospholipid bilayers only when both carried
      opposite charges. The slow exchange (in the EPR time scale) between membrane
      bound and free TOAC-14 allowed the calculation of the peptide's partition
      coefficient. The spectral line shapes were affected by aggregate size and degree
      of packing of the constituent molecules. It is proposed that pH, polarity, and
      lipid environment can affect the conformation of water-exposed regions of
      membrane-bound receptors, thereby playing a role in the mechanism of signal
      transduction.

PMID- 10904554
TI  - Monte Carlo simulation of multiple attack mechanism of beta-amylase-catalyzed
      reaction.
AB  - beta-Amylase (EC 3.2.1.2) produces maltose (dimer) from the nonreducing ends of
      alpha-1,4 glucosidic bonds of substrates like maltooligosaccharides, amylose, and
      amylopectin. The enzyme releases several maltose molecules from a single enzyme
      substrate complex without dissociation by multiple or repetitive attack
      containing many branching reaction paths. The Monte Carlo method was applied to
      the simulation of the beta-amylase-catalyzed reaction including the multiple
      attack mechanism. The simulation starts from a single enzyme molecule and a
      finite number of substrate molecules. The selection of the substrate by the
      enzyme and degree of multiple attack proceeds by random numbers produced from a
      computer. The simulation was carried out until the whole substrate and the
      intermediate molecules were consumed. The simulated data were compared with
      experimental data of sweet potato beta-amylase using heptamer, octamer, nanomer,
      and 11-mer as substrates. The only adjustable parameter for odd-numbered
      substrates was the probability of multiple attack, while an additional adjustable
      parameter (a correction factor due to low reactivity of tetramer) was needed for
      even-numbered substrates.

PMID- 10904555
TI  - Prediction and classification of alpha-turn types.
AB  - Tight turns play an important role in globular proteins from both the structural
      and functional points of view. Of tight turns, beta-turns and gamma-turns have
      been extensively studied, but alpha-turns were little investigated. Recently, a
      systematic search for alpha-turns was conducted by V. Pavone et al. [(1996)
      Biopolymers, Vol. 38, pp. 705-721] from 190 proteins (221 protein chains). They
      found 356 alpha-turns that were classified into nine different types according to
      their backbone trajectory features. In view of this new discovery, a sequence
      coupled model based on Markov chain theory is proposed for predicting the alpha
      turn types in proteins. The high rates of correct prediction by resubstitution
      test and jackknife test imply that that the formation of different alpha-turn
      types is evidently correlated with the sequence of a pentapeptide, and hence can
      be approximately predicted based on the sequence information of the pentapeptide
      alone, although the role of its interaction with the other part of a protein
      cannot be completely ignored. The algorithm presented here can also be used to
      conduct the prediction in which a distinction between alpha-turns and non-alpha
      turns is also required.

PMID- 10904556
TI  - Helix bundles and coiled coils in alpha-spectrin and tropomyosin: a theoretical
      CD study.
AB  - The dipole interaction model is used to investigate the effects of interactions
      between helices and supertwisting of helices by determining whether the predicted
      UV absorption and CD spectra for the three-helix bundle and coiled coil are
      significantly different from spectra for the single straight alpha-helix.
      Crystallographic data by Yan et al. for alpha-spectrin are used to construct a
      three-helix bundle of poly(L-alanine) modeling the protein. Backbone torsion
      angles represented by Fourier series are used to generate supertwisted helices
      and coiled coil models of poly(L-alanine) that have pitch, radius, and residue
      repeat similar to experimental crystallographic data on tropomyosin. Calculated
      CD spectra are compared with available experimental data. Theoretical spectra for
      the three-helix bundle and the supertwisted structures are quite similar to
      predictions for the straight alpha-helix of the same length with similar torsion
      angles, suggesting that CD is primarily dependent on the average backbone
      conformation and would not be a sensitive tool for distinguishing between single
      straight helices and closely packed or twisted alpha-helices.

PMID- 10904557
TI  - Single tryptophanyl substitutions affect the structure of apomyoglobin.
AB  - Mammalian myoglobins contain two tryptophanyl residues at the invariant positions
      A-5 (W7) and A-12 (W14) in the N-terminal region (A helix) of the protein
      molecule. To determine the contribution of each tryptophanyl residue to the
      structure and stability of myoglobin, recombinant proteins with single indole
      residue, i.e., W7 or W14, were obtained by site-directed mutagenesis. The mutant
      proteins, expressed in Escherichia coli, were found correctly folded, the far
      ultraviolet circular dichroism of both mutants as well as the Soret absorption
      being superimposed to that of wild type protein. The removal of the prosthetic
      group from mutant proteins determined a loss of helical content much larger than
      that observed in the case of wild type myoglobin. These results suggest that
      tryptophanyl residues can play a crucial role on globin folding and structure.

PMID- 10904558
TI  - Sleep related O2 desaturation in COPD patients with normoxaemia and mild
      hypoxyaemia.
AB  - It is unknown whether daytime features predict oxygenation during sleep in COPD
      patients with normoxaemia or mild hypoxaemia. In this study our purpose was to
      evaluate by a pulse oxymeter, nocturnal desaturation in 33 COPD with PaO2 > 60
      mmHg and to examine some daytime parameters as possible predictors of nocturnal
      hypoxaemia. A significant nocturnal desaturation has been defined by spending >
      or = 30% of total sleep-time with a TSTSaO2 < 90% > 30. According to this
      criterion we classified our patients in Desaturators (D) and Non Desaturators
      (ND). Our results showed that 39% of our patients were D and 61% ND. Among
      anthropometric and respiratory functional data we found that daytime SaO2B (r =
      0.74 p < 0.001) daytime PaO2 (r = 0.47 p < 0.01) and daytime PaCO2 (r = 0.45 p <
      0.05) were significantly correlated with the nocturnal oxygen desaturation and
      can predict the presence of sleep related hypoxaemia. In conclusion, our study
      confirms that a relatively high percentage of COPD patients with normoxaemia or
      borderline hypoxaemia exhibits significant nocturnal hypoxaemia. Further studies
      will suggest whether sleep related hypoxaemia deserves nocturnal oxygen therapy.

PMID- 10904559
TI  - Water role in STM imaging of organic films.

PMID- 10904560
TI  - Toxicity of Actinia equina (Cnidaria: Anthozoa) crude venom on cultured cells.
AB  - The toxicity of Cnidaria is a subject of high concern owing to its influence on
      human activities and public health and to the implications in ecological
      relationships between organisms. In order to simulate as much as possible the
      natural conditions and the consequences of stinging against injured cells, as
      well considering that Cnidarian venoms are located not only in nematocysts but
      also in tissues, the cytotoxicity and genotoxicity of crude extracts from
      nematocyst and surrounding tissues of the sea-anemone Actinia equina (Cnidaria:
      Anthozoa) were assessed on cultured fibroblasts (V79). The cytotoxicity was
      remarkable and cell survival was highly reduced at highest tested concentration
      (150,000 nematocysts/ml); using the Trypan blue dye exclusion test, only 40% of
      treated cells survived after the first hour of treatment and viable cells were
      not counted after the second hour. Also the results obtained utilizing the
      Neutral Red assay showed serious effects of crude toxin (only 31.5% and 12.6%
      cell survival after one and three hours respectively). Genotoxic effects were not
      observed at tested doses.

PMID- 10904561
TI  - Reduction in 222radon concentration due to water treatment processes.
AB  - In 40 samples of drinkable water taken from public fountains in the Province of
      Genoa determinations of 222Rn concentration were performed. The results were
      related to data obtained in a previous study on 222Rn concentration in spring
      water in the same areas, in order to assess a possible variation due to water
      treatment and to the aqueduct piping length. Radon concentration was also related
      to the main geographical areas in the Province and to the different geological
      formations. The average concentration was 0.92 +/- 0.86 Bq/l, and it can be
      related to equivalent dose to the population of 0.16 mSv/year. Our data show that
      water treatment processes cause a reduction in Radon concentration ranging
      between 58% and 93%, from picking up to utilization.

PMID- 10904562
TI  - Nontyphoidal Salmonella diarrhea in Thai children: a study at Bamrasnaradura
      Hospital, Nonthaburi, Thailand.
AB  - From July 1, 1994 to June 30, 1996, 394 children with Nontyphoidal Salmonella
      diarrhea were studied at Bamrasnaradura Infectious Disease Hospital in Thailand.
      The ages ranged from 1 month to 12 years (mean, 1.4 years). Eighty-seven per cent
      of patients were in the first 2 years of life. Diarrhea, mostly acute with watery
      stool and fever were the most common presenting symptoms. The duration of
      diarrhea ranged from 1 to 20 days (mean, 5.2 days). Salmonella group B was the
      most common serogroup (56.1%). Most isolates were multiresistant strains,
      however, they were all sensitive to norfloxacin. Four (1%) patients were HIV
      infected. Pneumonia found in 2 patients (0.5%) and septicemia in 1 patient
      (0.3%). None of the patients died. We conclude that nontyphoidal Salmonella
      diarrhea in children is still endemic in Thailand, especially among infants and
      high multidrug resistance occurs.

PMID- 10904563
TI  - Primary amenorrhoea: a retrospective study at Siriraj Hospital.
AB  - To determine the incidence of etiologic factors responsible for primary
      amenorrhoea in Siriraj Hospital on the basis of clinical examination and
      laboratory investigations. A retrospective study was performed from the records
      of patients who attended the Reproductive endocrine Clinic at Siriraj Hospital
      from 1 September 1992 to 31 August 1995. During the 3 years of the study period,
      there were 110 cases of primary amenorrhoea. One hundred and one cases were
      analyzed: nine cases were excluded because the patients lost follow-up before the
      final diagnosis could be concluded. The two most common etiologic factors were
      mullerian agenesis (39.65%) and gonadal dysgenesis (32.69%). Mean age of the
      patients when they first consulted the physicians was 22.45 +/- 6.06 years.
      Karyotyping was done on 28 of 32 cases of gonadal dysgenesis; 46,XX karyotype was
      found in 50 per cent and 45,XO in 14.29 per cent of analyzed cases. Clinical
      examination gave wrong diagnosis of absent uterus in 4 cases who were in the
      hypoestrogenic stage with hypoplastic uterus; ultrasonography and laparoscopy
      gave the wrong diagnosis in 1 case each in our report. These patients
      successfully menstruated after hormonal replacement therapy. The incidence of
      etiologic causes and cytogenetic study of primary amenorrhoea in our study is
      different from earlier reports. Racial and environmental differences may play a
      role in these differences. The facilities of diagnostic tools may also play a
      part. However, both clinical examination and many laboratory investigations have
      to be completed before final diagnosis of etiologic causes of primary amenorrhoea
      are elucidated. Diagnosis based on inadequate data can be misleading.

PMID- 10904564
TI  - Estradiol and follicle-stimulating hormone levels in oophorectomized women using
      vaginal estrogen.
AB  - To assess the changing estradiol (E2) and follicle-stimulating hormone (FSH)
      level in oophorectomized women using vaginal estrogen. Serum estradiol and FSH
      were evaluated in 32 oophorectomized women using a daily dose of 2 g base of 1.25
      mg vaginal conjugated equine estrogen (CEE) cream. The blood sample for hormone
      assay was collected 8-10 hours from the time of vaginal application. E2 and FSH
      levels were measured in the serum sample before and after commencing the study at
      4, 8 and 12 weeks using the time-resolved fluoroimmunoassay method. Serum
      estradiol significantly increased from baseline value at 4, 8 and 12 weeks. (Mean
      +/- SD of E2 value at 0, 4, 8, 12 weeks: 9.97 +/- 12.13, 249.83 +/- 170.46,
      299.38 +/- 190.65, 322.82 +/- 218.31 pmol/L, respectively, P < 0.05) On the other
      hand, serum FSH significantly decreased from baseline value at 4, 8 and 12 weeks.
      (Mean +/- SD of FSH value at 0, 4, 8, 12 weeks: 77.64 +/- 27.24, 40.33 +/- 21.64,
      38.84 +/- 22.33, 30.90 +/- 24.32 IU/L, respectively, P < 0.05) In conclusion, a
      daily dose of 2 g vaginal CEE cream raised the serum estradiol level close to the
      normal level in the follicular phase of the normal menstrual cycle. However, even
      though FSH significantly decreased it did not reach the premenopausal level.

PMID- 10904565
TI  - The impact of industrialization on road traffic accidents in Thailand.
AB  - Accompanying the socio-economic changes of Thailand in the past decade, road
      traffic accidents have become a leading cause of fatality. This study will
      identify the relationship between industrialization and the trend of fatalities
      from road traffic accidents. Observing per capita income and national industrial
      production, 1986 marked the beginning of the period of industrialization. Since
      that year, the mortality rate from road traffic accidents has rapidly increased.
      This trend occurred more among males, people between 15-35 years old and in the
      central region of the country. This trend is a warning to search for measures to
      prevent this harmful side effect of industrialization.

PMID- 10904566
TI  - Use of drugs and adverse reactions in medical inpatients.
AB  - An one-day survey of 111 medical inpatients admitted to four wards of the
      Department of Medicine, Chulalongkorn University Hospital was conducted. Its aim
      was to examine the differences in medication use patterns and incidence of
      adverse reaction to medication between young and old patients. The mean age and
      its standard deviation were 43.5 and 18.2 years respectively. Common medications
      used by these patients were antibiotics, paracetamol, parenteral fluid, peptic
      ulcer and gastritis remedies, vitamin and mineral supplements, and diuretics.
      Compared to the young patients, the elderly patients received more prescriptions
      for cardiovascular drugs and diuretics while receiving fewer prescriptions for
      vitamin and mineral supplements. Thai elderly medical inpatients had a higher
      rate of adverse reaction when compared to their young counterparts. Patients who
      received 6 medications or more were more likely to have an adverse reaction than
      those who received less than 6 items. The discipline of geriatric medicine may
      have a role in caring for the elderly patients in medical wards. A cohort study
      with a larger sample for determining causes or factors associated with adverse
      drug reactions is needed.

PMID- 10904567
TI  - Adolescent height: relationship to exercise, milk intake and parents' height.
AB  - The investigators studied the height of adolescents in the age range of 12 to 18
      years from 2 schools in Bangkok. Questionnaires asking their rates of organised
      exercise per week, of milk intake per day and their parental heights were given
      to a total of 545 male and 615 female students. The completed questionnaires were
      analyzed. We could categorize these subjects into 3 groups according to their
      heights which were Group I (height > 97th%-ile), Group II (height between 50
      97th%-ile) and Group III (height < 50th%-ile). Those in Group I had parents,
      whose height was significantly greater than those of the other groups. There was
      no difference in organized exercise among the 3 groups. Milk intake of female
      adolescents from Group I was significantly more than the other groups. It is
      concluded that parents' height in both males and females and milk intake in
      females contribute to a greater adolescent height.

PMID- 10904568
TI  - Health-related self-report (HRSR) scale: the diagnostic screening test for
      depression in Thai population.
AB  - In this study we introduced a health-related self-report (HRSR) diagnostic scale
      for detecting depression in Thai population. The scale composed of 20 symptom
      items including two objective signs (people said I look worried or sad) and
      previous suicidal attempt both of which were helpful in detecting and confirming
      depression and suicidal risk. There were 3 positive items (feel well, life is
      pleasant and meaningful and feel self-worth) which clearly distinguished normal
      subjects and depressed patients. The reliability coefficient (Chronbach's alpha)
      of the HRSR scale was 0.91 and was found to possess a clear factorial structure
      and clinical validity. The cut-off score at 30 gave 90.2 per cent specificity and
      85.3 per cent sensitivity for major depression. Score > or = 25 provided higher
      specify (93.4%) but lower sensitivity (75.1%) and could detect probable cases of
      depression or other mental illnesses in the community. Thus it can be used as a
      diagnostic screening instrument.

PMID- 10904569
TI  - Bronchodilatation effects of dry powder formoterol fumarate in asthmatic
      patients.
AB  - Ten asthmatic patients were enrolled in our study of the effects of dry powder
      formoterol fumarate. The onset was 2-5 minutes and a long duration of action
      (over 12 hours) appeared. The mean baseline FEV1 was 1.67 liters (49-74%). Mean
      reversibility was 17 per cent (range 15-19%). There was no adverse effect in this
      study.

PMID- 10904570
TI  - Macerated fetus in utero relating to intracranial angioma: report of 2 cases.
AB  - Two macerated fetuses in utero are presented. The mothers experienced no
      abnormalities during pregnancy. Both fetuses were found postmortem to have
      intracranial angiomas. In case 1, the angioma in the choroid plexus of the right
      lateral ventricle was associated with intraventricular and subarchnoid
      hemorrhages. There was additional angiomatosis in the leptomeninges and substance
      of the brain. In case 2, there was leptomeningeal angiomatosis with diffuse
      subarchnoid hemorrhage. It is suggested that spontaneous rupture of the angioma
      of the choroid plexus in case 1 and of the leptomeninges in case 2 resulted in
      immediate death of the fetuses with subsequent maceration in utero. Asymptomatic
      angioma of the fourth ventricular choroid plexus is also described in case 2
      because of its extreme rarity.

PMID- 10904571
TI  - Colchicine-induced myopathy in renal failure.
AB  - A 60 year-old woman with chronic renal failure developed acute proximal muscle
      weakness after receiving a regular dosage of colchicine. Elevation of muscle
      enzymes and electromyography were compatible with myopathy. Muscle biopsy
      revealed variation in muscle fiber size and few vacuolated fibers which were
      features of colchicine-induced myopathy. The clinical improvement and decreasing
      in muscle enzyme level occurred after colchicine withdrawal. Other potential
      causes of myopathy such as chronic renal failure and other drugs were ruled out.
      We suggested that colchicine should be used with caution in the presence of renal
      failure especially when other drugs which affect the metabolism of colchicine are
      also prescribed.

PMID- 10904572
TI  - Diabetic ketoacidosis and melioidosis in a child.
AB  - A case of 5 year old diabetic girl with melioidosis was reported. She presented
      with the symptoms and signs of intraabdominal infection, septicemia and diabetic
      ketoacidosis. Abdominal ultrasonography showed multiple splenic and liver
      abscesses, melioidosis was suspected. Hemoculture and pus culture yielded
      Burkholderia pseudomallei which was susceptible to ceftazidime and cotrimoxazole.
      Correction of fluid and electrolyte combined with insulin therapy and proper
      antibiotics resulted in a good outcome in this patient.

PMID- 10904573
TI  - Muscular hamartoma of the breast: a rare breast lesion containing smooth muscle.
AB  - Hamartoma of the breast is an uncommon entity, usually presenting as a well
      demarcated breast mass. Microscopically, the lesion is composed of mammary
      glandular component, fibrous stroma, adipose tissue, and smooth muscle in
      variable proportions. Among the variants of breast hamartoma, muscular hamartoma
      is rare. This lesion should be differentiated from other breast tumors that
      contain smooth muscle element. We report a breast lesion of a 36-year-old woman
      diagnosed as a muscular hamartoma in which the muscular component is cellular and
      some mitotic figures are present. The criteria to distinguish between benign and
      malignant smooth muscle lesions in the breast, emphasizing mitotic count, are
      also discussed.

PMID- 10904574
TI  - [Low-tech medicine for refugees. Medical aid on the powder keg].

PMID- 10904575
TI  - [Small intervention, large reimbursement].

PMID- 10904576
TI  - [Using nuclear medicine to assess backache].

PMID- 10904577
TI  - [Anxiety disorders in children].

PMID- 10904578
TI  - [Online search, II. Search in metaspheres].

PMID- 10904579
TI  - [The queen of literature research. DIMDI's new clothes].

PMID- 10904580
TI  - [Early cancer detection: what makes the Japanese so good?].

PMID- 10904581
TI  - [Substance dependence in the elderly. Gentle treatment of addiction].

PMID- 10904582
TI  - [Anxiety disorders in children and adolescents. Epidemiology, risk factors and
      intervention].
AB  - The article reviews the literature on anxiety disorders in children and
      adolescents. Anxiety disorders represent one of the most common disorders in
      children and adolescents, with a life-time prevalence of about 10%. In most
      studies, significantly more females than males met the diagnosis of anxiety
      disorders. Some factors that have been commonly found to be associated with
      anxiety disorders include parental psychopathology, familial dysfunction,
      negative life events, and behavioral inhibition. Anxiety co-occurs frequently
      with other disorders; it has a chronic course and most of the anxiety cases are
      psychosocially impaired in various areas of life. The article ends by giving an
      overview of various types of intervention strategies commonly used to treat
      children and adolescents with anxiety disorders.

PMID- 10904583
TI  - [The hyperkinetic child in ambulatory care. Therapeutic strategies for long-term
      care].
AB  - Children with a hyperkinetic disorder (attention deficit, hyperactivity,
      impulsiveness) should be diagnosed early in order to avoid difficulties in the
      family and with friends, and, in particular at school, and thus to positively
      influence the child's development. The present article discusses the definition,
      course, accompanying disorders and appropriate forms of treatment. Most important
      for outpatient treatment is the multimodal approach, in which various forms of
      therapy for the children and their families are integrated. Adequate outpatient
      treatment facilities must be made available in order to induce the children and
      their families to undergo long-term treatment.

PMID- 10904584
TI  - [Laser therapy of the eye for correction of refractive errors. A risk severe
      myopia?].

PMID- 10904585
TI  - [Report by the Federal Society of Pneumologists. Allergic bronchial asthma:
      chances for hyposensitization].

PMID- 10904586
TI  - [Polymorphic photodermatitis. 2: Spring perniosis, therapy and prevention].

PMID- 10904587
TI  - [Diagnostic quiz. Infected lung cysts. Lung abscess].

PMID- 10904589
TI  - [New propellant for inhaled corticoids. Deeper into the alveoli].

PMID- 10904588
TI  - [Type 2 diabetes. A new kind of insulin sensitizer at the door].

PMID- 10904590
TI  - [Injury-prone sports trends. Impact fracture with inline skates].

PMID- 10904592
TI  - [With chlorophyll against tumors?. Interview by Petra Eiden].

PMID- 10904593
TI  - [References for the physician in emergency service. When is abdominal pain an
      emergency?].

PMID- 10904591
TI  - [Drugs through the internet. Mouse click instead of prescription].

PMID- 10904594
TI  - [In vitro fertilization. The first gene check after fertilization?].

PMID- 10904595
TI  - [Unmasking diabetes in the early stage. Pathogenesis and diagnosis of diabetes
      mellitus in the elderly].

PMID- 10904596
TI  - [Diabetes therapy in the elderly for better prognosis and well-being. Which
      strategies are suitable?].
AB  - A specific and important aim of treatment in elderly diabetics is neither to
      induce nor aggravate geriatric syndromes. Clinical observations indicate that
      this goal can be achieved in the elderly diabetic only when the control of blood
      glucose, blood pressure and blood lipids meet the recommendations of the European
      NIDDM Policy Group for type 2 diabetics. In principle, the same possibilities for
      the treatment of diabetes apply to the elderly as to younger diabetics, with
      differences merely of priority. As a result of the manifold afflictions of
      geriatric patients, problems arise with the implementation of treatment. However,
      intensive individual training of the elderly diabetic is capable of preserving
      his/her independence.

PMID- 10904597
TI  - [Comprehensive diabetes therapy despite budget controls. Challenges for the
      general practice team].

PMID- 10904598
TI  - [Thromboembolism prevention with low-molecular-weight heparins. Risks, events and
      costs].

PMID- 10904599
TI  - [Early detection of colorectal carcinoma. Are you aware of the screening
      intervals?].

PMID- 10904600
TI  - [Migraine therapy in pregnancy. Paracetamol leads in acute therapy].

PMID- 10904602
TI  - [Basic therapy of rheumatoid arthritis. 1: Characterization and rules for
      administration].

PMID- 10904601
TI  - [Is prevention going backward? Increased cancer rate after prevention of coronary
      heart disease].

PMID- 10904603
TI  - [Diagnostic quiz. An unusual exanthema. Schonlein-Henoch purpura].

PMID- 10904604
TI  - [Correction of refractive errors. The "crutch" is reimbursed, not healing].

PMID- 10904605
TI  - [130/80 mmHg blood pressure goal. Can that be achieved, and if yes, how?].

PMID- 10904607
TI  - [Increased girth, thin arms. Unusual changes in HIV therapy].

PMID- 10904606
TI  - [Prandial glucose regulator for type 2 diabetic patients. Beta cells produce
      insulin according to need].

PMID- 10904608
TI  - [Every morning a stuffy nose, no known allergen so far? We reveal the source!].

PMID- 10904609
TI  - [Inaccuracies in mammography?. Interview by Petra Eiden].

PMID- 10904610
TI  - [Tips for medical emergency care. Panic patients: supportive talk as first aid].

PMID- 10904612
TI  - [Chronic pyelonephritis. Synopsis of laboratory values and ultrasound lead to
      diagnosis].
AB  - Bacteria or their antigens persisting in the kidneys may induce the classical
      type of chronic pyelonephritis (CP), which progresses slowly, and may finally
      result in end-stage renal failure requiring dialysis. Pyelonephrogenic strains
      enter uro-epithelial and renal epithelial cells--where they accumulate--or may
      invade the renal interstitium. Promoting factors are obstruction, reflux,
      urolithiasis, nephrolithiasis, pregnancy, diabetes mellitus, humoral and cellular
      immunodeficiencies, immunosuppression treatment (e.g. following transplants),
      autoimmune phenomena (antigenic mimicry). Therapy comprises the treatment of
      underlying disease, antibiotics as indicated by the resistogram, acidification of
      urine (L-methionine), i.v. immunoglobulins (IgM, IgG) and oral vaccination with
      lyophilized uropathogens.

PMID- 10904613
TI  - [Pyelonephritis in the diabetic patient. Acute risk for the kidney].

PMID- 10904611
TI  - [1999 Robert Koch Drug Award for enoxaparin. Safely preventing thromboembolism].

PMID- 10904614
TI  - [How the general practitioner can help prevent pyelonephritis. Suggestions for
      the practice team].

PMID- 10904615
TI  - [New knowledge about cancer and nutrition. 5 servings of fruit and vegetables per
      day prevent cancer].
AB  - On average, lacto-ovo-vegetarians develop cancer less often than their meat
      eating fellows. A particularly clear correlation exists between vegetable
      consumption and the reduction of the risk of developing cancer of the
      gastrointestinal tract or lung cancer. The factors responsible for the
      anticarcinogenic effects are not vitamins, minerals and ballast (fiber) alone,
      but also include in particular the secondary plant substances, whose numbers run
      into thousands. These substances act in a variety of different ways--for example
      carotinoids and flavonoids inhibit carcinogen-activating enzymes, phyto-estrogens
      and indoles have a modulating effect on the hormone metabolism, while saponins or
      sulfides stimulate the body's natural killer cells. Against this background, the
      German Society for Nutrition (Deutsche Gesellschaft fur Ernahrung) recommends the
      daily consumption of 375 grams of vegetables and about 250 to 300 grams of fruit.

PMID- 10904616
TI  - [Toxoplasmosis. 1: Risk factors and detection].

PMID- 10904617
TI  - [Surprise in backache and fever. Type A aortic dissection].

PMID- 10904619
TI  - [90% success rate. High tech against chronic tinnitus].

PMID- 10904618
TI  - [Diabetes networks. Initiatives from the base up].

PMID- 10904620
TI  - [Chronic inflammatory bowel diseases. Immunosuppressive drug saves on
      corticoids].

PMID- 10904621
TI  - [Hypertension plus diabetes. Lowering blood pressure is first priority].

PMID- 10904622
TI  - [Leukotriene antagonists against bronchial asthma. Not a replacement for
      steroids].

PMID- 10904623
TI  - [Long-term therapy with low dosage corticoids in rheumatology is well
      established].

PMID- 10904624
TI  - [Low dosage glucocorticoids in pneumology: the goal is a minimal maintenance
      dose].

PMID- 10904625
TI  - [Gastroenterology: corticoids have great value especially in acute therapy].

PMID- 10904626
TI  - [Glucocorticoids in dermatology: low-dose therapy preferred for a long time].

PMID- 10904627
TI  - [Unburdening your patients. Comprehensive program for weight loss].

PMID- 10904628
TI  - [What determines long-term outcome?].

PMID- 10904629
TI  - [Treatment concepts for overweight children. Power kids instead of frustration
      eating].

PMID- 10904630
TI  - [Liver diagnostics. Conservative alternatives to CT?. Interview by Petra Eiden].

PMID- 10904631
TI  - [Urinary incontinence. Bringing the bladder under control again].

PMID- 10904632
TI  - [Laboratory values in acute myocardial infarct. New markers improve diagnosis].

PMID- 10904633
TI  - [Psychotherapy: the earlier, the better. Postponing therapy harms the patient and
      health insurance].
AB  - Psychotherapeutic measures produce good results providing they are initiated in
      good time, and the treatment is appropriate to the problem and given by a
      competent therapist. There are, however, numerous difficulties that can result in
      the psychogenic disorders becoming chronic. The poor public acceptance of
      psychotherapy is based on fear and the negative perception of this form of
      treatment. It would appear to be of great importance to improve the image of
      psychotherapy to avoid chronicity.

PMID- 10904634
TI  - [Functional physical complaints. Guideline for diagnosis and treatment of
      somatoform disorders].
AB  - Although physical symptoms are the main reason why people go to the doctor, in
      many cases no unequivocal underlying organic disturbances are to be found, not
      even during subsequent visits to the doctor (Kroenke & Mangelsdorff, 1989).
      Frequently, the patient's previous history contains pointers for other physical
      complaints that also had no unequivocal organic etiology. This group of patients,
      who often present their problem in a very complaining fashion, are considered by
      many physicians to be difficult, bothersome, and ungrateful. Until quite recently
      it was assumed that the chances of successful treatment in these patients were
      poor. Accordingly, an American standard textbook of psychiatry recommends, as the
      main aim of the treatment, avoiding iatrogenic harm (Barsky, 1988). The present
      article wishes to make it clear that such a pessimistic assessment of the
      therapeutic outcome is no longer warranted. A positive effect can now be achieved
      with ambulatory psychotherapeutic measures both in the offices of general
      practitioners or internists, and in hospitals offering integrative-psychosomatic
      treatment on an inpatient basis.

PMID- 10904635
TI  - [Psychotherapy--(not) a case for general practice? Suggestions for the practice
      team].

PMID- 10904636
TI  - [Facets of scaly erythema. Morphologically and descriptively oriented
      dermatological diagnosis (6)].

PMID- 10904637
TI  - [Diabetic ulcer: reaching for the scalpel--but not amputation!].

PMID- 10904638
TI  - [Warts: no therapy: no therapy modifies spontaneous course!].

PMID- 10904639
TI  - [Lip enhancement--what can happen to cosmetically conscious patients].

PMID- 10904640
TI  - [Successful trio for wound inflammation: compression, drainage, antibiosis].

PMID- 10904641
TI  - [For these "boils" systemic antibiotics will not help].

PMID- 10904642
TI  - [Lower leg ulcers and decubitus ulcer. Optimal wound management improves relative
      quality of life].

PMID- 10904643
TI  - [Respecting subjective perception of the patient. The "quality of life" concept
      changes medicine].

PMID- 10904644
TI  - [Physical therapy in rheumatology. 2: Cold, electro-, balneo- and ergotherapy].

PMID- 10904645
TI  - [Young woman with refractory vomiting. Superior mesenteric artery syndrome].

PMID- 10904646
TI  - [Emnid survey of medical care. Patients are also discontent with politics].

PMID- 10904647
TI  - [Do you treat adolescents? Therapy becomes a high wire act. Interview by Werner
      Loosen].

PMID- 10904648
TI  - [Flu vaccine in the fall. Pneumococcal vaccination at the same time!].

PMID- 10904649
TI  - [The weak site of the stronger sex. Phytotherapy often helps the prostate
      patient].

PMID- 10904650
TI  - [Why is it important to have a good normal fee?].

PMID- 10904651
TI  - [Drugs in practice].

PMID- 10904652
TI  - [Vaccine against poverty].

PMID- 10904653
TI  - [Poliomyelitis--a step closer to eradication].

PMID- 10904654
TI  - [Telemedicine].

PMID- 10904655
TI  - [Is it possible to reduce the use of antibiotics?].

PMID- 10904656
TI  - [Tuberculosis in Norwegian children--diagnostic challenges].
AB  - BACKGROUND: Each year, 20-25 Norwegian children below the age of 18 are diagnosed
      with tuberculosis in Norway. MATERIAL AND METHODS: As a demonstration of various
      difficulties in the work-up and diagnosis of tuberculosis, we present eight
      infected children aged 15 months to 10 years. RESULTS: Children often contract
      the infection from adults and may develop serious manifestations including
      miliary tuberculosis and meningitis. The symptoms are often not specific and
      tuberculosis may be mistaken for other diseases. Delay and inappropriate
      diagnostics may have deleterious consequences. INTERPRETATION: The main message
      is to start treatment upon clinical suspicion of tuberculosis. It is mandatory to
      sample the necessary biological material for microbiological tests before
      starting treatment.

PMID- 10904657
TI  - [Antibiotic resistance of blood culture isolates in Buskerud in 1994 and 1998].
AB  - BACKGROUND: The increase of antimicrobial resistance has caused general concern
      world-wide. There is a high risk that this development will also occur in Norway.
      Several efforts have been made to prevent the emergence of antimicrobial
      resistance. A national surveillance programme for antimicrobial resistance has
      been started, and new legislation has made resistance surveillance programmes
      compulsory in every Norwegian hospital. Local surveillance of resistance is among
      the most important measures. MATERIAL AND METHODS: We have undertaken
      surveillance of all blood culture isolates from the County of Buskerud in 1994
      and 1998. Detection of antibiotic resistance-patterns were undertaken for all
      blood culture isolates in the two years using disc diffusion method (Rosco
      diagnostics, Taastrup, Denmark). We also looked at the consumption of
      antimicrobial agents in Buskerud Central Hospital in 1998. A total of 628
      isolates from 572 patients were included in the study, 279 isolates from 1994 and
      349 from 1998. RESULTS: We still have low occurrence of resistance in Buskerud,
      and there has been no significant increase during the four-year period.
      INTERPRETATION: The low prevalence of antibiotic resistance reflects the
      restrictive antibiotic policy in Norway. Therefore, we find it important to
      continue this policy and to continue close surveillance of the development of
      antibiotic resistance.

PMID- 10904658
TI  - [Utilization of antibiotics in and outside of health facilities in Norway in
      1998].
AB  - BACKGROUND: Data on overall consumption of antibacterials are an important basis
      for measures against antibiotic resistance. MATERIAL AND METHODS: Salesdata of
      antibacterials (ATC group J01) for systemic use was collected from all hospitals
      in Norway for the year 1998. The sale to hospitals was subtracted from the total
      sale of antibacterials in Norway and the consumption for outpatient settings was
      estimated. RESULTS: The total use of antibacterials for systemic use in Norway
      was 14.4 DDD/1,000 inhabitants/day in 1998, which has been regarded as low. The
      use of antibacterials in hospitals was 7.5% of the total market, i.e. 1.09
      DDD/1,000 inhabitants/day. The estimated use in ambulatory practice was 13.3
      DDD/1,000 inhabitants/day. Different consumption patterns in the two settings
      were observed. The penicillins comprised around half of the antibacterials in
      both settings although the use of beta-laktamase sensitive penicillins
      represented a higher fraction in the outpatient setting. Cephalosporins
      represented 16% of the use of antibacterials in hospitals while the tetracyclines
      are the second most used antibacterial group outside hospitals. The use of newer
      broad spectrum antibacterials such as the quinolones are now increasing in Norway
      both inside and outside hospitals. INTERPRETATION: Relatively high consumption of
      penicillins supports the assumption that antibacterial resistance is low in
      Norway. It is, however, important to continue to follow the consumption of
      antibacterials in order to detect a potential negative trend early and instigate
      efforts like information, to possibly change the trend. It also offers the
      potential of measuring effects of legislative changes and informational efforts
      as well as defining the need for further investigation of drug therapy
      traditions.

PMID- 10904659
TI  - [Meningococcal disease in Africa--epidemiology and prevention].
AB  - Neisseria meningitidis is one of the most common causes of purulent meningitis
      all over the world. Large epidemics caused by meningococci have spread during the
      last decade throughout vast areas of Africa, also outside the region referred to
      as the classic "Meningitis Belt". Globally, this organism each year causes about
      300,000 cases and 30,000 deaths; most of these are children. Meningococci of
      serogroup A cause a major part of these epidemics, and a remarkable feature of
      the epidemical situation is that the bacteria differ very little in antigenic
      properties as they belong to the same clonal group of meningococci. Immunization
      with safe and effective vaccines is the most efficient way of combatting these
      epidemics. The currently available polysaccharide vaccines against serogroup. A
      meningococcal disease do not induce long-term immunological memory and do not
      provide adequate protection of children below two years of age. There is an
      urgent need for a vaccine that induces long-term immunological memory in all age
      groups, so it can be included in the routine vaccination program. In contrast to
      serogroup C, the development of conjugate vaccines against serogroup A
      meningococcal disease has not yielded the positive results hoped for. The
      development of alternative protein-based vaccines therefore needs to be
      intensified.

PMID- 10904660
TI  - [Malnutrition and infections in children--a destructive interplay with global
      dimensions].
AB  - BACKGROUND: Seven out of ten deaths among the world's children are caused by
      infectious diseases. Malnutrition is a contributing cause in more than half of
      the children's deaths. At present, interventions against such diseases in
      children are the most cost-effective way of reducing the world's morbidity and
      mortality. MATERIAL AND METHODS: This paper discusses how nutritional status
      affects the immune defence, and vice versa. General protein and energy
      malnutrition and some specific nutrients are discussed. The paper is based on
      review of recent literature found in Medline, and key references in the papers
      identified. RESULTS: Malnutrition is the most common cause of acquired immune
      deficiency in children. Malnourished children are especially prone to develop
      persistent diarrhoea, which in turn aggravates the nutritional status. Iron
      deficiency may be caused or worsened by hookworm and a number of other
      gastrointestinal infections. There are indications that iron deficiency in itself
      reduces the immune defence. Vitamin A supplements have reduced the mortality of
      measles and other infectious diseases. Some studies have shown reduced vertical
      transmission of HIV when pregnant women get vitamin A supplements. Chronic
      diarrhoea may cause zinc deficiency which may aggravate the diarrhoea. In areas
      where the general population's zinc status is marginal, zinc supplementation has
      reduced the incidence and duration of persistent diarrhoea. INTERPRETATION: The
      interaction between malnutrition and common infections in children causes a
      considerable fraction of the global burden of disease, yet so far this is not
      reflected in research, which mainly targets the diseases of the rich.

PMID- 10904661
TI  - [Guidelines for diagnosis and treatment of acute urinary tract problems in
      women].
AB  - BACKGROUND: Available guidelines for the management of symptoms of lower urinary
      tract infections (UTI) in women give conflicting recommendations. MATERIAL AND
      METHODS: We searched The Cochrane Library, Medline and other sources for evidence
      that met explicit inclusion criteria for the relevant options and outcomes
      identified. The validity of included studies was assessed. Draft recommendations
      were widely circulated and discussed in focus groups with patients and physician
      assistants. RESULTS: The probability that a woman with dysuria or frequency has
      bacteriuria, is 80%. The probability of UTI given a negative result of a dipstick
      test is 50%. Evidence suggests that antibiotics will rapidly relieve symptoms,
      but there are limited data from placebo-controlled randomised trials. Population
      based studies show that many women do not visit physicians for symptoms of UTI.
      Women with symptoms of UTI can be treated with antibiotics without examination of
      the urine. Women with earlier episodes of UTI can be offered treatment by
      telephone. Antibiotics for three days is sufficient based on eradication of
      bacteriuria. Women should be seen by a physician if the symptoms are atypical.
      INTERPRETATION: Implementing these guidelines could result in better service to
      women with UTIs. More evidence about the effects of antibiotics and other
      treatments is needed.

PMID- 10904662
TI  - [Guidelines for diagnosis and treatment of sore throat].
AB  - BACKGROUND: Available guidelines for the diagnosis and treatment of sore throat
      give conflicting recommendations. Our aim was to develop evidence-based
      guidelines. MATERIAL AND METHODS: We searched The Cochrane Library, Medline and
      other sources for systematic reviews and other evidence that met explicit
      inclusion criteria for all of the relevant options and outcomes we identified.
      The validity of included studies was assessed. Draft recommendations based on
      assessment of this evidence were widely circulated and discussed in focus groups
      with patients and physician assistants. RESULTS: Throat infections are self
      limiting and complications rare. Penicillin shortens the duration of symptoms in
      tonsillitis caused by beta-haemolytic streptococci and reduces the risk of
      complications. Penicillin has adverse effects and increases the risk of
      reinfections. Patients with sore throat should usually be treated without
      antibiotics. Visiting a physician is normally unnecessary. Antibiotics should be
      considered in serious cases or if the patient prefers this, but should only be
      prescribed for throat infections caused by beta-haemolytic streptococci. The
      diagnosis should be based on clinical criteria and a rapid antigen test in cases
      of doubt. INTERPRETATION: Benefits of antibiotics must be weighed against harms.
      Patients should be given good information and involved in decision-making if they
      want antibiotics.

PMID- 10904664
TI  - [A patient with high fever, ascites and rash].

PMID- 10904663
TI  - [Is terminal sedation active euthanasia?].
AB  - In order to be able to discuss the issue of whether or not terminal sedation is,
      or may be conceived of as, a form of help in dying, one needs to be very clear as
      to the meaning of the terms "help in dying" and "terminal sedation". In this
      article, we suggest what we take to be detailed and precise definitions of the
      two forms of voluntary help in dying--euthanasia and physician-assisted suicide.
      Our definitions (interpretations) basically draw on the Dutch experience and
      understanding. The Dutch approach implies that acts of abstention, i.e.,
      withholding and withdrawing treatment, and pain and symptom treatment with
      possible life-shortening effect, including terminal sedation, are to be
      considered "normal medical practice". Furthermore, death is seen by almost all
      parties as having natural causes in all of these acts. We also suggest that
      "palliative sedation" should substitute the expression "terminal sedation".
      Furthermore, we discuss on what grounds this treatment strategy may be induced,
      including a presentation of criteria and guidelines that must be met; the issue
      of documentation of the strategy; palliative sedation in the light of the ethical
      principle of double effect; and in what way euthanasia could be concealed as
      palliative sedation. In closing, we comment briefly on the phenomenon of large
      differences between published cohorts with regard to the frequency of use of
      palliative sedation. This treatment strategy is open to be challenged both
      clinically and ethically, and all parties would benefit from a continuous debate
      over the legitimacy of, and the clinical need for, palliative sedation.

PMID- 10904665
TI  - [Choice of analgesics to breast feeding women].

PMID- 10904666
TI  - [Will the use of still image electronic referrals save costs?].
AB  - BACKGROUND: The use of still images in an electronic referral makes it possible
      for patients with uncomplicated skin disorders to receive treatment at their
      local health clinic by their own physician. The aim of this study was to analyse
      whether investing in technology to forward still images via telemedicine is cost
      effective and to assess how many municipalities in the counties of Troms and
      Finnmark that have a sufficient workload to reach this requirement. MATERIAL AND
      METHODS: The additional costs of using still images were compared to patient
      travel costs to the University Hospital of Tromso. RESULTS: The results showed
      that whether the use of still image telemedicine is cost-effective or not,
      depends on distance and annual workload. Given the assumption in this study, 18
      out of 44 municipalities have a sufficient number of patients with a
      dermatological problem to make telemedicine cost-effective. INTERPRETATION: Less
      than half of the municipalities in the two northernmost counties have an
      efficiency potential in using still images. However, telemedicine may be
      justified because it save time for patients and it increases equal access to
      care.

PMID- 10904667
TI  - [Telemedicine collaboration between the Rikshospitalet and the Ulleval hospital].
AB  - BACKGROUND: During the last two years the Intervention Centre at the Nation
      Hospital of Norway and Ulleval Hospital have pursued a research programme in
      telemedicine aimed at exploring the potential of inter-hospital collaboration.
      MATERIAL AND METHODS: Both hospitals established a communication network between
      operating rooms and lecture halls. Sound and video from minimally invasive
      surgical and radiology procedures were transmitted on a wide bandwidth ATM
      network (34 Mbits/s) to gain experience with the use of telemedicine for
      educational purposes and the treatment of patients. RESULTS: Evaluations of
      technical off-line and clinical line transmissions have given us helpful
      information about the potential of telemedicine and what it will take to utilise
      this potential. With the MPEG2 standard, a wide bandwidth network yields
      sufficient sound and image quality for educational and clinical collaboration.
      However, multimedia communication requires changes in the organisation to secure
      quality of service in relation to technical management and telemedical
      production. INTERPRETATION: Inter-hospital collaboration on telemedicine may be a
      resource in clinical practice, facilitating professional enhancements,
      particularly in surgery, radiology and internal medicine. Changes in the
      organisation are needed, but they are feasible.

PMID- 10904668
TI  - [Future with telemedicine].

PMID- 10904669
TI  - [Internalization--legislative barriers and solutions].

PMID- 10904670
TI  - [The standard of documentation and impact of recommendations in clinical
      guidelines].

PMID- 10904671
TI  - [Pathology--a changing discipline].

PMID- 10904672
TI  - [The limited value of clinical experience].

PMID- 10904674
TI  - [In Process Citation]

PMID- 10904673
TI  - [HLA-B27 in Bechterew's disease].

PMID- 10904675
TI  - [Mental retardation and disorders of cortical development].

PMID- 10904676
TI  - [Neuropsychological phenotypes of genetic diseases].

PMID- 10904677
TI  - [Recent advances in the genetics and physiopathology of X chromosomal mental
      retardation].

PMID- 10904678
TI  - [In Process Citation]

PMID- 10904679
TI  - [Diagnostic approach to metabolic myopathies].

PMID- 10904680
TI  - [Diagnosis of molecular biology in muscular dystrophies].

PMID- 10904681
TI  - [In Process Citation]

PMID- 10904682
TI  - [In Process Citation]

PMID- 10904683
TI  - [BREV: an assessment battery for cognitive deficits in children 4 to 9 years old.
      Results of a normative study in 500 children].

PMID- 10904684
TI  - [Evaluation of fetal hemodynamics].

PMID- 10904685
TI  - [Syncope in the child and adolescent].

PMID- 10904686
TI  - [Tachycardia in the newborn infant and in the infant].

PMID- 10904687
TI  - [Disorders of heart conduction: surveillance and treatment].

PMID- 10904688
TI  - [Principal indications and surveillance of anti-arrhythmia treatment in the
      child].

PMID- 10904689
TI  - [Dysfunction of the brain stem and congenital heart defects].

PMID- 10904690
TI  - [The concept of medical information regarding specificity and child care].

PMID- 10904691
TI  - [Some points on ethics in communication and information in pediatrics].

PMID- 10904692
TI  - [Right to information by the child and adolescent].

PMID- 10904693
TI  - [Information, consent and refusal by the child in biomedical research].

PMID- 10904694
TI  - [Information on health education for the child].

PMID- 10904695
TI  - [Transmission of health messages in school, or practical application of theory].

PMID- 10904696
TI  - [In Process Citation]

PMID- 10904697
TI  - [CIAO: an interactive information and prevention tool for the young in
      Switzerland].

PMID- 10904698
TI  - [Means and conditions for educating the well child and the ill child].

PMID- 10904699
TI  - [In Process Citation]

PMID- 10904700
TI  - [In Process Citation]

PMID- 10904702
TI  - [In Process Citation]

PMID- 10904701
TI  - [In Process Citation]

PMID- 10904703
TI  - [In Process Citation]

PMID- 10904704
TI  - [Information regarding pain].

PMID- 10904705
TI  - [Defense mechanisms during stress regarding disclosure of a chronic disease in
      children in adolescents].

PMID- 10904706
TI  - [Information for the epileptic child].

PMID- 10904707
TI  - [In Process Citation]

PMID- 10904708
TI  - [Information for the child of parents with cancer].

PMID- 10904709
TI  - [Important progress in infant nutrition].

PMID- 10904711
TI  - [In Process Citation]

PMID- 10904710
TI  - [In Process Citation]

PMID- 10904712
TI  - [Noninvasive ventilation of the child].

PMID- 10904713
TI  - [Noninvasive ventilation in chronic lung obstruction and bronchopulmonary
      diseases].

PMID- 10904714
TI  - [Noninvasive ventilation at home in neuromuscular diseases].

PMID- 10904715
TI  - [Allergic contact dermatoses in the child].

PMID- 10904716
TI  - [Toxic dermal reactions in the child].

PMID- 10904717
TI  - [Molecular pathology of transcription factors implicated in the development of
      the anterior hypophysis].

PMID- 10904719
TI  - [In Process Citation]

PMID- 10904718
TI  - [Molecular pathology of the GHRH receptor].

PMID- 10904720
TI  - [In Process Citation]

PMID- 10904721
TI  - [Quality of life in ambulatory pediatrics: value of the patient care team].

PMID- 10904722
TI  - [Methodology for studying the quality of life of children in clinical research].

PMID- 10904723
TI  - [Quality of life in pediatric rheumatology].

PMID- 10904724
TI  - [Approach for evaluating the quality of life using the CIDIH1 (International
      Classification of Deficits, Incapacity and Handicaps). Application to
      polyarticular forms of juvenile arthritis].

PMID- 10904725
TI  - [Quality of life of children after organ transplantation].

PMID- 10904727
TI  - [Probiotic effect on reproduction of intestinal flora of the infant].

PMID- 10904726
TI  - [Value of an indicator of the health status of children suffering from a severe
      illness: exemplified by brain tumors].

PMID- 10904728
TI  - [Intestinal flora, probiotics and effects on the intestinal IgA immune response].

PMID- 10904729
TI  - [Effect of a probiotic on the intestinal barrier in a model of allergy to milk
      proteins of the cow].

PMID- 10904730
TI  - [Bacterial flora in the infant and intestinal immunity: Implication and prospects
      for infant food with probiotics].

PMID- 10904731
TI  - [Place of ambulatory pediatrics with respect to the adolescent of today].

PMID- 10904732
TI  - [Liaison work in management of suicidal adolescents in pediatrics in a general
      hospital].

PMID- 10904733
TI  - [Follow-up of suicidal adolescents: value of dual management].

PMID- 10904734
TI  - [Work of illness, work of grief, and work of adolescence, or the adolescence of a
      child with a chronic disease].

PMID- 10904735
TI  - [Time and passage of the adolescent from the pediatrician to the physician for
      adults].

PMID- 10904736
TI  - [Physiologic aspects of lung circulation in adjustment to extra-uterine life].

PMID- 10904737
TI  - [Postnatal alveolar development: regulatory factors and consequences of neonatal
      influences].

PMID- 10904738
TI  - [In Process Citation]

PMID- 10904739
TI  - [Pathology of lung development in diaphragmatic hernia].

PMID- 10904740
TI  - [In Process Citation]

PMID- 10904741
TI  - [In Process Citation]

PMID- 10904742
TI  - [In Process Citation]

PMID- 10904743
TI  - [In Process Citation]

PMID- 10904744
TI  - [In Process Citation]

PMID- 10904745
TI  - [Evolution of modalities for managing pregnant addicted women and their children.
      Pregnancy and Addiction Study Group].

PMID- 10904746
TI  - [Cocaine and pregnancy].

PMID- 10904747
TI  - [Perinatal pharmacology of opiates].

PMID- 10904748
TI  - [In Process Citation]

PMID- 10904749
TI  - [Antibiotic therapy in pregnancy: importance of rational use].

PMID- 10904751
TI  - [Health education in pregnancy].

PMID- 10904750
TI  - [Human immunodeficiency virus: current pregnancy aspects].

PMID- 10904752
TI  - [Neonatal infections with genital mycoplasmas].

PMID- 10904753
TI  - [Severe mycoplasma infections].

PMID- 10904754
TI  - [Respiratory tract infections caused by mycoplasmas].

PMID- 10904756
TI  - [In Process Citation]

PMID- 10904757
TI  - [Long-term follow-up of urinary tract abnormalities diagnosed in utero].

PMID- 10904755
TI  - [Biological diagnosis of infections caused by mycoplasmas].

PMID- 10904758
TI  - [Ethical aspects of managing severe uropathies in the antenatal and postnatal
      period].

PMID- 10904760
TI  - [Rapid diagnostic tests of community-acquired infection].

PMID- 10904759
TI  - [Biochemical markers of bacterial infection].

PMID- 10904761
TI  - [Role of soluble antigens in rapid diagnosis of bacterial infections].

PMID- 10904762
TI  - [Application of DNA probes in bacteriology].

PMID- 10904763
TI  - [Value of video electroencephalography in neonatology].

PMID- 10904764
TI  - [Influence of convulsive crises on the immature brain].

PMID- 10904765
TI  - [Brain malformations and metabolic diseases].

PMID- 10904766
TI  - [In Process Citation]

PMID- 10904767
TI  - [EPIPAGE: epidemiologic study of very premature infants. Protocol of the survey].

PMID- 10904768
TI  - [In Process Citation]

PMID- 10904769
TI  - [Current status and prospects for symptomatic treatment of respiratory tract
      infections in mucoviscidosis].

PMID- 10904770
TI  - [Is the impact of managing mucoviscidosis measurable?].

PMID- 10904771
TI  - [Correction of CFTR anomalies: pharmacological approach].

PMID- 10904772
TI  - [Genetic therapy in mucoviscidosis].

PMID- 10904773
TI  - [Genes and the environment].

PMID- 10904774
TI  - [Congenital malformations: cleft lip and/or palate].

PMID- 10904775
TI  - [Pharmacogenetics in pediatrics].

PMID- 10904776
TI  - [Water electrolyte balance in the newborn infant and in the infant].

PMID- 10904777
TI  - [In Process Citation]

PMID- 10904778
TI  - [Humanitarian activity: urgency? Development? What place does it have in active
      pediatrics?].

PMID- 10904779
TI  - [Evaluation in humanitarian health and action].

PMID- 10904780
TI  - [Moldavie, you said Moldavie? Planning and realization of an ECHO Program
      (Emergency Program of the European Union) by a group of pediatricians liberated
      in a country of the former USSR].

PMID- 10904781
TI  - [Evaluation approach in sexual ambiguity: Reims experience from a retrospective
      study].

PMID- 10904782
TI  - [In Process Citation]

PMID- 10904783
TI  - [Role of allergy and infections in asthma development].

PMID- 10904784
TI  - [Are inhaled corticosteroids dangerous?].

PMID- 10904785
TI  - [Has the symptomatology of asthma in the child changed over the last 30 years?].

PMID- 10904786
TI  - [Toward a strategy of prevention in the child? The Prevention Group I].

PMID- 10904787
TI  - [Management of risk of fetal exposure to drugs. Historical aspects].

PMID- 10904788
TI  - [Preclinical trials for predicting fetal risk].

PMID- 10904789
TI  - [Methods for studying drug risk during pregnancy].

PMID- 10904791
TI  - [In Process Citation]

PMID- 10904790
TI  - [Antiretroviral drugs and pregnancy: apropos of an alert regarding mitochondrial
      pathology and nucleoside analogs].

PMID- 10904792
TI  - [Bronchiolitis obliterans after bone marrow graft].

PMID- 10904793
TI  - Betahistine effects on cochlear blood flow: from the laboratory to the clinic.
AB  - The development of laser Doppler flowmetry techniques has contributed greatly to
      the study of cochlear blood flow (CBF). In animal models, intravenous betahistine
      dihydrochloride clearly increased CBF in a dose-dependent manner. This effect was
      greater in the cochlear vasculature than in the systemic vascular bed. The
      effects of betahistine were blocked by the alpha 2-antagonist idazoxan, thus
      suggesting an interaction between histaminergic and presynaptic adrenergic
      receptors. This was further supported by studies investigating the effects of
      electrical stimulation on CBF. Local (round window membrane) application of
      betahistine did not affect CBF, but had a non-specific effect on cochlear
      electrophysiology. This indicates that the receptors for betahistine vascular
      effects in the inner ear are most likely located in the modiolar artery. More
      recently, laser Doppler flowmetry techniques have been applied to human subjects.
      It has been shown that intratympanic application of adrenaline affects CBF and
      that this blood flow is under vigorous sympathetic control. Electrical
      stimulation has also been used to obtain measures of dynamic responsiveness in
      human subjects. This results in an increase in CBF, which is dependent on the
      intensity of the stimulation. Preliminary evidence indicates that this procedure
      can provide a standardized measure of the dynamic properties of CBF and may
      provide a means to differentially identify patients with compromised vasculature.

PMID- 10904794
TI  - Betahistine reduces the resting firing rate of vestibular receptors in the frog.
AB  - Although betahistine is widely used in the treatment of vertigo, it remains
      unclear whether it directly affects the vestibular system at the peripheral
      level. The effects of betahistine were therefore assessed in an isolated
      preparation of frog semicircular canal. Betahistine was administered either in
      the endolymphatic or the perilymphatic fluid and the ampullar receptor potential
      and mass nerve discharge were recorded at rest and during mechanical stimulation.
      Endolymphatic administration was without effect. In contrast, perilymphatic
      administration resulted in a marked reduction in ampullar receptor resting
      discharge, although the mechanically evoked responses were only slightly
      affected. As vertigo is generally caused by sudden and uncontrolled changes in
      the resting discharge of vestibular receptors, the ability of betahistine to
      reduce the resting firing rate of vestibular receptors is thought to contribute
      to its anti-vertigo actions.

PMID- 10904795
TI  - Betahistine, vestibular function and compensation: in vitro studies of vestibular
      function and plasticity.
AB  - Histamine has an excitatory action on rat medial vestibular nucleus neurones in
      vitro, an effect that is mediated by histamine H1 and H2 receptors. Betahistine,
      which is a weak agonist at the H1 receptor and a moderate antagonist at the
      presynaptic H3 autoreceptor, weakly excites medial vestibular nucleus cells but
      antagonizes their responses to histamine. Experiments were carried out on rat
      medial vestibular nucleus cells in vitro using slices prepared from animals that
      had undergone unilateral labyrinthectomy (UL). There was a significant increase
      in the intrinsic excitability of medial vestibular nucleus cells in the rostral
      region of the ipsi-lesional nucleus within 4 h post-UL, which was sustained for
      the following week. These changes in intrinsic excitability of the medial
      vestibular nucleus neurones were abolished in animals that were not exposed to
      the secretion of stress hormones that normally occurs following UL. Histamine is
      also released in response to the stress associated with vestibular dysfunction.
      It is possible that the beneficial effects of betahistine on vestibular
      compensation are related to an interaction between histaminergic receptors
      activated by the parallel release of histamine and the activation of
      glucocorticoid receptors through the activation of the stress axis. Further study
      of the interactions between histamine receptors and the activation of the stress
      axis may be useful in understanding the effects of betahistine on vestibular
      plasticity.

PMID- 10904796
TI  - Vestibular compensation in the cat: the role of the histaminergic system.
AB  - Histamine is thought to be involved in the recovery of vestibular function as
      histaminergic medications are effective in vestibular-related syndromes. We
      conducted studies in the cat to assess the effects of betahistine (a histamine
      like substance) on the behavioural recovery process after unilateral vestibular
      neurectomy (UVN). We also investigated histamine immunoreactivity changes in the
      vestibular and tuberomammillary nuclei of betahistine-treated lesioned cats
      compared with untreated and unlesioned cats. Betahistine strongly accelerated the
      behavioural recovery process after UVN, with a time benefit of approximately 2
      weeks for both static posture (support surface) and dynamic equilibrium function
      (locomotor balance) compared with untreated animals. A bilateral decrease in
      histamine immunoreactivity was seen in both acute and compensated UVN cats; this
      effect was strongly accentuated with betahistine treatment. In conclusion, the
      results indicate that vestibular lesion reduces histamine staining due to an
      increase in histamine release in the vestibular and tuberomammillary nuclei that
      promote vestibular recovery. Betahistine dihydrochloride should contribute to
      this process by acting on both the presynaptic histamine H3 and postsynaptic
      histamine H1 receptors.

PMID- 10904797
TI  - Vestibular ocular reflexes in Meniere's disease patients evaluated by passive
      high frequency head rotation (yaw) and sidewards acceleration.
AB  - Despite the fact that vertigo is the most apparent complaint at the onset of
      Meniere's disease, standard vestibular examination seldom shows vestibular
      function loss in the early phase. In this study, three relatively advanced
      diagnostic tests (passive high frequency head shaking, passive head impulse test
      and sidewards linear acceleration) were applied to trace vestibular function loss
      in the early phase in 25 patients with possible Meniere's disease (American
      Academy of Otolaryngology-Head and Neck Surgery 1995 criteria); one test (passive
      high frequency head shaking) was also conducted in 20 chronic definite Meniere's
      disease patients. Head movements were induced by a head shaker and whole-body
      linear translation by a motor-driven linear slit. Eye movements were detected by
      electro-oculography (head shaking) and the scleral coil technique (impulse test
      and linear translation). Standard vestibular examination showed no vestibular
      function loss in the early phase patient group. In contrast, 17 out of 25
      patients (68%) showed a phase lag upon head shaking that was 1-2 degrees larger
      than the 95% confidence interval in healthy subjects; the remaining 8 patients
      showed a normal phase lag. Gain was normal in all 25 patients. In the chronic
      patient group, standard vestibular examination was abnormal (calorics) in 16 out
      of 20 patients (60%) and 18 out of 20 (90%) showed an abnormal phase on passive
      head shaking. In 11 of the 25 early phase patients (44%), an increased latency
      was observed in the response to a passive head impulse to one side. The side to
      which the abnormal latency occurred did not correspond to the documented or
      reported side of the hearing loss in 2 out of the 11 patients. The amplitude of
      ocular counter rolling induced by sidewards sinusoidal translation was reduced in
      17 out of the 25 early phase Meniere's disease patients, of whom 6 showed a
      normal head impulse and head shaking test. Our findings indicate that vestibular
      function loss occurs in Meniere's disease patients within 9 months of the first
      vertigo attack. Also, the results support the hypothesis that, at least in some
      patients, function loss in the statolith system might precede function loss in
      the horizontal canals.

PMID- 10904798
TI  - Medical treatment in Meniere's disease: avoiding vestibular neurectomy and
      facilitating postoperative compensation.
AB  - The efficacy of medical treatment in preventing the need for vestibular
      neurectomy (VN) in patients with disabling Meniere's disease, and in facilitating
      postoperative compensation of equilibrium after VN, was investigated. Ninety-five
      patients with classic symptoms of unilateral incapacitating Meniere's disease
      were included. Patients were treated with either 16 mg betahistine three-times
      daily (n = 49) or 125 mg acetazolamide once-daily (n = 46) for 6 months. The
      study showed that marked benefit was achieved in 51 of the 95 patients, of whom
      significantly more were in the betahistine group than in the acetazolamide group
      [32 (65%) vs 19 (41%); p < 0.05]. Twenty-seven patients in the acetazolamide
      group and 17 in the betahistine group experienced no benefit from medical
      treatment and therefore underwent VN. Twelve patients in the betahistine group
      and 6 in the acetazolamide group eventually experienced a relapse and thus also
      underwent VN. Therefore 62 patients in total underwent VN. Following surgery,
      patients were given medical treatment in an attempt to facilitate vestibular
      compensation; 28 received betahistine (16 mg three-times daily) and 34 received
      cinnarizine (25 mg three-times daily) for 3 months. The patients treated with
      betahistine had a shorter period of disability and significantly better results
      on rotatory testing. In conclusion we recommend the use of betahistine in
      patients who have undergone VN.

PMID- 10904799
TI  - A review of medical treatment for Meniere's disease.
AB  - A review of the literature on drug therapy for Meniere's disease was made using
      Medline to search for all publications between January 1978 and September 1998. A
      total of 152 publications were identified that specifically dealt with medical
      treatment for Meniere's disease. Only betahistine and diuretics appear to have
      proven efficacy in double-blind studies on the long-term control of vertigo. No
      treatment has a proven beneficial effect on hearing levels or on the long-term
      evolution of the disease. Recent publications have proposed a role for the
      intratympanic use of medication, mainly aminoglycosides, for control of vertigo.
      We conclude this review by proposing a strategy for the medical treatment of
      Meniere's disease.

PMID- 10904800
TI  - [Aminoglycoside antibiotics. The problems in creating new preparations].

PMID- 10904801
TI  - [The cis-trans isomerization of aromatic heptaenes catalyzed by sulfur and
      phosphorus compounds].
AB  - It was shown that sulfur and phosphorus compounds (sodium thiosulfate, sodium
      tripolyphosphate, sodium hexametaphosphate, monosodium phosphate) catalyze cis
      trans isomerization of aromatic heptaens. Preparative method of levorin
      isomerezation at the presence of sodium thiosulfate was elaborated. The isolated
      product was a fully trans-isomer.

PMID- 10904802
TI  - [The antimicrobial activity and acute toxicity of the polymer salts of
      gentamycin].
AB  - By neutralization of copolymers of N-(2-hydroxypropyl) methacrylamide with
      acrylic acid and copolymers of N-vinylpyrrolidone with crotonic and p
      crotonoylaminophenoxyacetic acids in the presence of gentamycin, water-soluble
      polymer salts containing from 10 to 25 mass% of gentamycin were obtained. These
      salts regardless of gentamycin content completely retain high level of
      antimicrobial activity of gentamycin against Staphylococcus spp. and Escherichia
      coli and are characterized by less (by more than one order of magnitude) acute
      toxicity.

PMID- 10904803
TI  - [The use of cycloferon in the therapy of experimental herpetic keratitis].
AB  - The cycloferon efficacy was investigated in the treatment of experimental
      herpesvirus kerato-conjunctivitis in rabbits. The model was demonstrated to
      reflect the main aspects of herpesvirus eye lesions in humans. Cycloferon
      application similarly to that of known interferon inducer poludan has been shown
      to enhance processes of inflammation and subsequent regeneration of eye tissues
      as well as to decrease mortality of animals due to the generalization of
      infection.

PMID- 10904804
TI  - [The chemotherapeutic efficacy of ciprofloxacin and lomefloxacin in the
      inhalation method of infecting white mice with tularemia].
AB  - Peculiarities of the protective effect of ciprofloxacin and lomefloxacin were
      studied and the optimal regimens of their use were determined in multifactor
      experiments on albino mice infected with finally dispersed aerosol of the
      virulent strain of the European subspecies of Francisella tularensis. As for
      protective effect, the fluoroquinolones provided high percentage of the animal
      survival. The optimal course of the treatment was at least 7 days. The interval
      of 0 to 48 hours between the infection and the start of the treatment had no
      statistically significant effect on chemotherapeutic efficacy of
      fluoroquinolones.

PMID- 10904805
TI  - [The activation of phagocytosis by recombinant human tumor necrosis factor-beta].
AB  - The functional activity of phagocytic cells of various types was studied in white
      non-inbred mice by administering recombinant human tumor necrosis beta (rhTNF
      beta). It was shown that rhTNF-beta increased phagocytic activity of the
      peritoneal exudate, spleen and liver macrophages as well as blood polynuclears.
      Stimulation of neutrophils was demonstrated in earlier times after administration
      of the preparation as compared to macrophages (3 h and 24 h, respectively). The
      duration of the macrophage activation effect and its expression depended on the
      dose of the preparation and were the most notable when rhTNF-beta was
      administered in doses of 10(3)-10(5) U/20 g. The addition of reopolyglucin, the
      polysaccharide filler, didn't remove a stimulatory effect of rhTNF-beta on
      macrophages, but influenced its dynamics. Multiple administration of the
      preparation didn't cause the phagocytosis stimulation effect.

PMID- 10904806
TI  - [The results and characteristics of the mupirocin (Bactroban) sanative treatment
      of intranasal Staphylococcus carriers in a large hospital].
AB  - The action of mupirocin as a nasal ointment (Bactroban) was studied on intranasal
      carriers of the hospital staphylococcal strains. The study included 37 medical
      workers from different and mainly problem units of the large general hospital.
      The tolerability of the ointment was good. After the Bactroban use no
      complications of the patients were recorded. The efficacy of Bacroban by the
      microbiological criteria in total amounted to 100 per cent. The eradication of
      methicillin resistant Staphylococcus aureus (MRSA) was observed in 93 per cent of
      the cases. A decrease of the level of the nasal passages dissemination by MRSA
      and methicillin resistant coagulase-negative staphylococci (MRSC) up to such low
      titers as 100 and 90 per cent was stated. No difference in the action of
      Bactroban on MRSA, MSSA and MRSC was noted. The bacteriological monitoring for 3
      to 4 months revealed a change of the staphylococcal strains in 94 per cent of the
      cases, recolonization by the same staphylococcal strain in 19 per cent,
      recolonization by some another staphylococcal strains in 33 per cent and no
      recolonization in 14 per cent. A stable decrease of staphylococcal strains was
      possible with simultaneous Bactroban sanitation of all the bacterial carriers of
      the hospital or its isolated unit.

PMID- 10904807
TI  - [The diagnostic and therapeutic characteristics of inflammatory urogenital
      diseases in women associated with Ureaplasma urealyticum].
AB  - Complex examination of 40 female in- and outpatients at the age 20 to 42 years
      with inflammatory urogenital diseases was performed. To verify the diagnosis,
      current clinical, microbiological, endoscopic and ultrasonic procedure were used.
      It was shown that the inflammatory processes in the urogenital tracts were mainly
      due to association of opportunistic and/or pathogenic organisms. Optimization of
      antibacterial therapy of urogenital infections was found possible with using
      homeopathic agents in the complex therapy. The significance of cooperation of the
      allied specialists in the choice of the examination and therapy policy for female
      patients with inflammatory urogenital diseases is indicated.

PMID- 10904808
TI  - [Stages in the improvement of drug therapy at a polyclinic].
AB  - Within 1968-1997 the authors studied the steps of introduction of the
      achievements of the medical science, technology and pharmacology to therapy of
      exacerbations and complications of peptic ulcer (PU). The scientific and
      practical value of endoscopic, histological, biochemical and bacteriological
      examinations in the improvement of the methods of pharmacotherapy of
      exacerbations and complications of PU was shown. Three phases of the PU
      development were indicated by the clinical signs and results of
      esophagogastroduodenoscopy, target biopsy and histological examinations. These
      data and available scientific achievements were assumed as a basis for the design
      of optimal drug combinations and their introduction to the medical practice. The
      use of such combinations made it possible to prevent relapses and life
      threatening complications of the disease in the overwhelming majority of the
      patients. The best results of the pharmacotherapy were recorded in the years
      (1988-1997) when the drug combinations began to be used. The combinations
      provided eradication of Helicobacter pylori in the gastroduodenal mucosa and it
      was proved that in all the patients with PU and the relapsing lesions in the
      duodenum and in the overwhelming majority of the patients with gastric ulcer the
      disease developed at the background of chronic active gastroduodenitis associated
      with H.pylori. The success of the pharmacotherapy in the patients with PU was due
      to the use of the rational combinations of antibacterial and antisecretory
      agents.

PMID- 10904810
TI  - Ministers ban seal branding program.

PMID- 10904809
TI  - [The antibacterial therapy of severe pneumonia].

PMID- 10904811
TI  - Dockings slashed.

PMID- 10904812
TI  - Paralysis tick research.

PMID- 10904813
TI  - Criteria used by employers to select new graduate employees.
AB  - OBJECTIVE: To find out what criteria and methods are used by Australian employers
      to select new graduates to work in their practices. DESIGN: Questionnaires were
      completed by 258 employers and the responses were analysed using the SAS system.
      RESULTS: During selection, employers placed most reliance on formal interviews or
      visits to the practice. These occasions were used to assess the applicant's
      personal qualities including their ability to interact effectively with clients
      and colleagues. Employers used resumes mainly in selection of applicants to
      interview and many discounted nominated referees as being insufficiently
      critical. Academic knowledge was regarded as less important than personal
      qualities and very few employers reported using gender as a basis for selection.
      CONCLUSIONS: Senior veterinary students need to be aware of the importance placed
      by employers on interpersonal skills and personal qualities and should make every
      effort to engage in practical work, paid work and other activities that will help
      develop these attributes. They should be conscious that practitioners with whom
      they work may be contacted by potential employers and they should learn to
      present themselves realistically in a resume.

PMID- 10904814
TI  - Actinobacillus suis infection in pigs in Australia.
AB  - This is the first report of the isolation of Actinobacillus suis in association
      with significant disease among preweaned pigs in Australia. Sudden deaths
      occurred in preweaned piglets at one facility and enlarged joints, particularly
      the stifles and tarsi, occurred at another. Isolates with the biochemical
      phenotype and apx genotype profile of A suis were cultured from affected piglets.
      Both facilities were of high health status and one had undergone a recent
      depopulation, disinfection and sow repopulation process. Reviewing initial
      reports of A suis disease overseas, it is apparent that outbreaks occurred
      sporadically in various locations, with disease occurring among the herds
      involved for some months only, before development of immunity. A suis disease is
      now considered an emerging disease on high health status farms.

PMID- 10904815
TI  - Disseminated Mycobacterium avium infection in a dog with chronic diarrhoea.
AB  - A 3-year-old Maltese-cross dog presented with a 4-month history of chronic
      diarrhoea and inappetence. Poorly regenerative anaemia, leukocytosis and
      hypoproteinaemia were evident on several occasions. Biopsies of stomach, duodenum
      and colon revealed marked infiltration of mucosae by macrophages containing many
      acid-fast bacilli. Similar organisms were numerous in a faecal smear. Melaena,
      hematochezia and severe abdominal pain developed and were unresponsive to
      therapy. Following euthanasia and necropsy, histiocytic cells containing acid
      fast bacilli were found throughout the gastrointestinal tract, mesenteric and
      peripheral lymph nodes, spleen, liver, kidney and lungs. The organism was
      identified as Mycobacterium avium by bacterial culture and polymerase chain
      reaction testing.

PMID- 10904816
TI  - Ventral midline caesarean section for dystocia secondary to failure to dilate the
      cervix in three alpacas.
AB  - Three alpacas that presented with dystocia characterised by failure of the cervix
      to dilate, underwent caesarean section. Surgery on each animal was performed
      through a ventral midline incision under general anaesthesia. Two live crias were
      delivered and one cria was dead at delivery. All three alpacas had retained
      foetal membranes for a period of 12 h to 4 d and one developed uterine prolapse,
      which was replaced using sedation and epidural anaesthesia. There were no
      complications associated with the surgical procedure and all three alpacas went
      on to have confirmed pregnancies. Caesarean section through a ventral midline
      incision should be considered an alternative for treatment of difficult dystocias
      in alpacas.

PMID- 10904817
TI  - Ten tips to ease the transition from student to veterinarian.

PMID- 10904818
TI  - Virulent Newcastle disease virus in Australia: in through the 'back door'.

PMID- 10904819
TI  - Towards an understanding of equine pleuropneumonia: factors relevant for control.
AB  - OBJECTIVE: To review relevant literature on factors associated with the
      development of equine pleuropneumonia. DESIGN: A review of the literature using a
      range of databases including Current Contents, Medline, ChemAbstracts, Biological
      Abstracts and CAB and a comprehensive search strategy which involved use of
      keywords, author and subject category searches. Additional sources included
      review of articles cited by key accumulated references. RESULTS: Since the early
      years of this century, many of the "gaps" in our knowledge of the pathogenesis of
      this disease have been filled. We now know that equine pleuropneumonia results
      from contamination of the lower respiratory tract with bacteria similar to the
      normal oropharyngeal microbiota of the horse and that transportation of any mode,
      especially over long distances (and consequently with no or short rest periods),
      is the single most important predisposing factor for this disease. This is
      associated with restraint of horses such that they are unable to lower their
      heads, which leads to increased opportunity for lower respiratory tract
      contamination and a reduced opportunity for clearance. Strenuous exercise also
      results in lower respiratory tract contamination and exercise subsequent to
      transportation exerts additive detrimental effects on the defenses of the lower
      respiratory tract. CLINICAL IMPLICATIONS: While modern veterinary medicine and
      surgery have significantly reduced the death rate from pleuropneumonia, horses
      that develop the disease have a high probability of not returning to their prior
      use. This underscores the importance of developing the most effective strategies
      for its prevention.

PMID- 10904821
TI  - Clinical abnormalities detected in post-race examinations of poorly performing
      Standardbreds.
AB  - OBJECTIVE: To describe the clinical abnormalities found on post-race examination
      of poorly performing Standardbreds. METHOD: The results of 541 post-race
      veterinary examinations on Standardbreds were analysed. The horses were selected
      for examination by the stipendiary stewards on the basis of poor performance from
      a population of approximately 20,000 runners which competed at Harold Park
      Paceway, Sydney. RESULTS: Clinical abnormalities were detected on post-race
      examination in 264 of the 541 poorly performing horses. Some horses displayed
      more than one abnormality. Twenty three individual abnormalities were reported.
      Seventy three horses had suffered interference-type injuries (cross firing,
      scalping, over reaching) during the race. Lameness was the second most commonly
      found abnormality (n = 60), with 73% of these lamenesses being in a forelimb.
      Twenty nine horses had sacroiliac pain (representing 10.6% of the abnormalities
      detected). Poor recovery, exercise induced pulmonary haemorrhage, respiratory
      infection or nasal discharge, gluteal pain, unilateral nasal haemorrhage and
      mouth injuries complete the list of the ten most common findings. CONCLUSION:
      Interference-type injuries, lameness and sacroiliac pain were the most common
      abnormalities found on post-race examination of Standardbreds, which performed
      poorly.

PMID- 10904820
TI  - EEG changes in 4-week-old lambs in response to castration, tail docking and
      mulesing.
AB  - OBJECTIVE: To interpret changes in EEG in relation to perceived pain of
      castration, mulesing and docking in lambs. DESIGN: Analysis of covariance
      (randomised block design) to determine the effects of treatment on eight
      bandwidths of the EEG frequency spectrum. PROCEDURE: Ninety-eight, 3- to 4-week
      old lambs were subjected to one of seven treatments: castration, tail docking,
      mulesing, ear tagging, sham shearing, formalin injection (to induce lameness) and
      handling. EEG was recorded for 15 min before treatment, during treatment, and for
      15 min after treatment. RESULTS: Consistently lower mean power values across all
      bandwidths of the EEG were found at the time of mulesing and docking than at
      handling and shearing (P < 0.01). Formalin injection resulted in lower power
      values than handling and shearing (P < 0.01). Castration had lower power values
      than handling and shearing. Similarly, for 15 min after treatment, mulesing and
      formalin injection had significantly lower power values than handling, shearing,
      ear tagging and castration (P < 0.05). CONCLUSION: The consistent effects
      associated with mulesing, docking and castration compared to handling, shearing
      and ear tagging suggest that mulesing at both the time of treatment and during 15
      min after treatment results in a response that is similar to that of induced
      lameness. Docking and castration result in a response at the time of treatment
      that is similar to induced lameness and mulesing, but during 15 min after
      treatment is similar to the non-noxious control treatments. However, the
      depressing effects on the mean power values are the reverse of that anticipated
      from a previously developed pain model, highlighting the need for further
      research to develop this technology to evaluate pain associated with husbandry
      procedures.

PMID- 10904823
TI  - [Address for the opening ceremonies of the GEM 1999-2000].

PMID- 10904822
TI  - Changes in liver copper concentration of thoroughbred foals from birth to 160
      days of age and the effect of prenatal copper supplementation of their dams.
AB  - OBJECTIVES: To monitor the change in liver copper concentration of Thoroughbred
      foals from birth to 160 days of age and to determine the effects of
      supplementation by two injections of copper edetate given to dams in late
      gestation on the liver copper concentration of their foals at birth. PROCEDURE:
      Ten mares pregnant to the same stallion were randomised into two groups on the
      basis of age, liver copper concentration and expected foaling date. The treatment
      group mares were given 100 mg and 250 mg copper edetate intramuscularly during
      the ninth and tenth months of gestation respectively. Foals had liver biopsies
      taken weekly in the first month of life, then monthly for four months. Foals were
      euthanased at 160 days of age; liver samples were taken and the copper
      concentrations were determined. RESULTS: Two distinct patterns of age dependent
      decline in liver copper concentration were evident. The mean (+/- SD) liver
      copper concentration of the foals was high at birth (374 +/- 130 mg/kg DM), and
      for seven it declined to adult values by 160 days of age (21 +/- 6 mg/kg DM). In
      three foals the decline was at a slower rate than in the other seven and at 160
      days of age the mean concentration was 162 +/- 32 mg/kg DM. Repeated measures
      analysis showed significant differences between each biopsy (P < 0.01) and
      between 'normal' and 'accumulator' foals (P < 0.002). Copper injections given to
      mares in late pregnancy had no effect on the liver copper concentration of foals
      at birth. CONCLUSIONS: The significance of the two patterns of age dependant
      decline in liver copper concentration is unknown. Parenteral copper
      supplementation of the dam in late gestation had no effect on the liver copper
      concentration of the foal at birth.

PMID- 10904824
TI  - [Treatment of pseudarthrosis of the carpal scaphoid bone by percutaneous pinning.
      Apropos of 74 cases].
AB  - From 1985 to 1997, 74 patients was operated of scaphoid non union at the Kassab
      Institute by a percutaneous pinning as described by Galluccio. The average age is
      30 years with an extreme from 17 to 48 years. Union was obtained after an average
      of two years and six months. In 12 cases the delay was superior than three years.
      Functionally, pain is a constant cause of consultations and the majority of
      patients presented a reduction of the mobility sector (80%) and the strength of
      grasp (70%). Anatomically, it is particularly a pseudarthrosis stage II a of
      Alnot, and type I b of our classification. An immobilisation post-operative
      during one month is the rule. The analysis of results at an average of four
      years, revealed 91% of clinical recovery. Radiographically, the union is obtained
      in 89% of cases. Our fails (11%), are explained by an inadequate mounting and
      particularly by the length of pseudarthrosis. Compared to other means of
      synthesis, the percutaneous pinning of Galluccio, is an inexpensive technique,
      easily and rapid, which permit to obtain an interesting results particularly in
      the recent pseudarthrosis (evolution delay below three years).

PMID- 10904825
TI  - Avascular nontraumatic necrosis of the scaphoid. Preiser's disease?
AB  - Twenty-two cases of nontraumatic avascular necrosis of the scaphoid are reported.
      In ten cases a metabolic cause could be revealed; for the other 12 cases no
      etiology could be established. Twelve were treated with a proximal row
      carpectomy, ten had a very satisfactory result, one was not satisfied and had to
      be converted into a wrist arthrodesis and one is in doubt.

PMID- 10904826
TI  - [Neurolysis of the median nerve in the carpal canal using a mini-invasive
      approach. Apropos of a prospective series of 138 cases].
AB  - INTRODUCTION: The aim of this study was to assess the results of a prospective
      study of 138 cases with carpal tunnel syndrome operated on by a percutaneous
      technique. METHOD: One hundred and twenty-nine patients (108 women and 21 men,
      with a mean age of 49.9 years) underwent preoperative assessment via a
      questionnaire and a clinical examination (the Weber test, buckle test, Kapandji
      test, Tinel test, Phalen test, Vainio test and grip force assessment). The
      surgical technique was singularised by the insertion of a probe cannula in the
      carpal tunnel so that the blade could be guided during annular ligament section.
      RESULTS: The results were assessed at one, three and six months follow-up: 98.5%
      very good and good results were obtained (Kelly criteria); two patients presented
      with an algodystrophic syndrome. No vascular, tendinous or neurological
      complications were noted, and the procedure was in no instance switched to an
      open technique. DISCUSSION: The main advantages of this technique are a rapid
      recuperation of hand function, with an average of 22.6 days off work, a low
      complication rate, and simple equipment.

PMID- 10904827
TI  - [The effect of surgical technic of the cost of surgical treatment of carpal
      tunnel syndrome].
AB  - INTRODUCTION: Many publications have shown the efficiency along with the
      harmlessness of endoscopic release, in the idiopathic carpal tunnel syndrome.
      Some advantages have appeared such as an increase in post-operative well-being, a
      quicker recovery, hence a shorter sick leave. We wanted to know wether these
      advantages meant a reduced cost price for the community. METHOD: Since 1997, a
      hundred patient belonging to the social security system have been treated
      according to one of the three following methods: the Agee technique endoscopic
      release, isolated section of annular anterior carpal ligament, section-plasty. To
      calculate the cost, surgery and hospitalization cost price, post-operative
      paramedical services and daily payments have been taken into account. RESULTS:
      For a working subject, the endoscopic carpal tunnel release has enabled to save
      about 40% of the total cost, compared with the usual technique, mainly due to a
      shorter sick leave. Likewise, the section-plasty has proved to save 17% of the
      cost. DISCUSSION: The parameters which were taken into account in the total cost
      together with their calculation are controversial. The main problem of the study
      lies in the limited number of working subjects. Therefore, studying larger series
      would enable to confirm the interest of one method or the other.

PMID- 10904828
TI  - [Extension osteotomy of the long metacarpal bones. A therapeutic solution to
      repairing flexion defects. Apropos of 14 cases].
AB  - Fourteen extension osteotomies were performed in 13 patients with angular
      metacarpal malunion. Surgery was indicated by the limitation of mobility, the
      reduction in gripping capacity, and pain following digitopalmar grasping
      movements. After surgery, the patients regained good articular mobility. However,
      in 60% of cases a teno-arthrolysis was required upon removal of consolidation
      hardware to restore digital function. The operation allowed pain relief in two
      thirds of the patient population; in the remaining subjects, pain was experienced
      when making grasping movements. At the final examination, in the majority of
      cases gripping strength was similar to that of the contralateral hand. In
      conclusion, correction of angular malunion by extension osteotomy is a demanding
      procedure, and whenever possible should be avoided by a precise reduction of the
      metacarpal fracture during initial surgery. A fractured metacarpal with a palmar
      angulation of over 15 degrees should systematically be reduced and fixed if
      unstable.

PMID- 10904829
TI  - [Linburg-Comstock syndrome. Epidemiologic and anatomic study, clinical
      applications].
AB  - The Linburg-Comstock (LC) syndrome is distinguished by the inability to actively
      flex the interphalangeal (IP) joint of the thumb without simultaneously flexing
      the distal IP joint of the index finger. Any resistance to this 'parasitic'
      reaction causes pain on the palmar side of the wrist or in the distal part of the
      forearm; this is due to an anomalous tendinous connection between the flexor
      pollicus longus (FPL) and the flexor digitorum profundus (FDP). An
      epidemiological study was carried out on 264 individuals (a total of 528 hands
      were examined), and the LC syndrome was found in 98 subjects (37%); women were
      more frequently affected than men, and bilaterally rather than unilaterally. In
      addition, we dissected 26 fresh cadaver upper limbs, and in seven cases found an
      anomalous connection between FPL and FDP. We also examined the case of a young
      violinist with bilateral LC syndrome, who complained of pain in the distal part
      of the left forearm after prolonged musical exercises. Surgical investigation
      determined a complete fusion between FPL and FDP of the index with a common
      tendon. Treatment consisted of splitting this common tendon to form two separate
      tendons, thereby permitting a certain degree of independence between the thumb
      and index finger, and which considerably improved the violinist's musical
      performance. A review of the literature showed that there was a large quantity of
      anatomical descriptions available on these types of connection. Certain
      publications also provide an extremely precise report on the anthropological
      significance of these anomalies.

PMID- 10904830
TI  - [A retrospective study of 69 primary rhizarthrosis surgically treated by total
      trapeziectomy followed in 34 cases by interpositional tendinoplasty and in 35
      cases by suspensioplasty].
AB  - INTRODUCTION: We compare retrospectively two groups of total trapezectomy did as
      treatment for primary osteoarthritis of trapeziometacarpal joint combined in 34
      cases with tendon interposition arthroplasty (group A) and in 35 cases with
      suspensioplasty (group B). METHOD: In group A an 'anchovy' was made with half
      band of the abductor pollicis longus tendon and the palmarus longus tendon; in
      group B the same tendon samples were rolled around the flexor capi radialis
      tendon. The follow up is at least 18 months. RESULTS: Strength was nearly the
      same in the two groups. The suspensioplasty of the group B allows a better
      stability after trapezectomy than the anchovy of the group A, but with a small
      decrease in range of motion, without functional consequence. In both groups of
      patients, the range of motion was good. In the group B, the persistent pain was
      more frequent than in group A. Patients were satisfied with the ability of
      perform activities of daily life, but working patients were bothered by poor
      endurance. There was no statistical correlation between the power of the thumb
      and thumb shortening, but there was one between increasing of hyperextension of
      thumb metacarpophalangeal joint and decreasing power of pinch. DISCUSSION: Since
      the suspensioplasty has been tightenedless, the relief of pain has been better in
      the group B. Overall, the results in the two groups were nearly the same; the two
      procedures studied are satisfactory in most cases, but their result is too often
      inadequate with performance at work.

PMID- 10904831
TI  - Cross stitch peripheral tendon repair: a mechanical comparison with core stitch
      techniques.
AB  - The purpose of this experimental study was to compare certain mechanical
      properties of a true epitendineal cross stitch suture with simple and double
      locking core tendon repairs. Using tensile strength and tendon lengthening until
      gap formation as measurement parameters, these three types of repair were tested
      in human flexor and extensor tendons from fresh cadavers. The peripheral cross
      stitch and the locked core repairs were found to have a greater lengthening
      capacity than the simple core suture, whereas the latter significantly better
      withstood axial load. Our findings established that, at least when used as a true
      epitendinous suture, the cross stitch technique alone was not suited for the
      repair of severed tendons. However, its design is particularly useful in
      preventing the suture site from potentially restrictive bulking.

PMID- 10904832
TI  - [Vascularized surgical rotation of a bi-articular trapezoid-trapeziometacarpal
      complex for the treatment of severe rhizarthrosis of the thumb].
AB  - A new surgical procedure has been conceived to avoid persistent pain and to
      restore the functionality and pinch strength of the basal joint of the thumb
      destroyed by degenerative osteoarthritis. Since January 1998 a double total joint
      transposition was performed on eight patients, switching the trapezoid-metacarpal
      joint and the trapezio-metacarpal joint. A 180 degrees rotation of the bi
      articular complex (trapezoid-trapezio-metacarpal joints) in its entirety was
      achieved, while preserving the intrinsic ligaments and vascular supply insured by
      the dorsal branch of the radial artery; the Cardan conformation in Physics of the
      trapezoid-metacarpal joint provided complete thumb motion. TECHNIQUE: skin dorso
      radial approach of the wrist; arteriolysis of the dorsal branch of the radial
      artery at the anatomic snuff box and at its entrance into the first
      intermetacarpal space; metaphyseal osteotomy of the first and second metacarpal;
      capsulotomy all around the bi-articular complex; transfer and rotation of the
      trapezoid-trapezio-metacarpal bi-articular complex together with the dorsal
      branch of radial artery; osteotomy stabilisation by Kirschner wires; capsulo
      ligamentous reconstruction; plaster slab immobilisation. Four weeks later the
      thumb moves actively; hand therapy starts six weeks post-operatively. Clinical
      and radiological controls were performed at two, four and six weeks, tomography
      at three months post-operation. Clinical assessment for three patients showed
      three good results and for the other five showed excellent outcomes, resulting in
      complete motion, stability of the first metacarpal and restored painless pinch
      strength of the thumb. Today the trapezoid-metacarpal joint seems to ensure pain
      relief, mobility and to solve the instability due to the collapse of the thumb
      column by restoring the bone chain of the first metacarpal ray.

PMID- 10904833
TI  - Genetics of idiopathic dilated cardiomyopathy.
AB  - Familial dilated cardiomyopathy (DCM) should be an "evidence-based" diagnosis
      derived from clinical and echocardiographic screening of informed and consenting
      relatives of index patients, and on the examination of clinical reports for
      deceased relatives. Most familial dilated cardiomyopathy pedigrees show an
      autosomal pattern of inheritance. Very few of them are X-linked and matrilinear.
      Autosomal recessive inheritance is difficult to be assessed in an evidence-based
      setting. By linkage analysis, several loci, but no disease gene, have been
      identified. At present, few cases of familial dilated cardiomyopathy can benefit
      of a molecular diagnosis. The diagnosis of dystrophin defect-related dilated
      cardiomyopathy is important for patients and families, especially for carrier
      detection. These patients present X-linked inheritance, dominant cardiac
      involvement and raised levels of serum creatine phosphokinase. Defects of the
      glycoprotein complex associated to dystrophin (DAG) are rare skeletal muscle
      diseases with possible cardiac involvement. Mitochondrial diseases, both pure
      cardiomyopathies and multiorgan syndromes involving the heart, are associated to
      defects of mitochondrial DNA genes or of nuclear genes coding for mitochondrial
      proteins. Barth's syndrome develops in male children with granulocytopenia,
      dilated cardiomyopathy, and methylglutaconic aciduria. Cardiomyopathies with
      atrioventricular block are observed in hemochromatosis, Emery-Dreifuss syndrome,
      desmin storage disease, and in isolated familial dilated cardiomyopathy. Actin
      defects were recently identified in 2 unrelated patients with familial dilated
      cardiomyopathy. Desmin defects were also recently identified in 1 familial
      dilated cardiomyopathy. The overall knowledge, although in progression, is still
      limited. Clinical family screening identifies familial forms, preclinical cases,
      and inheritance pattern. By candidate gene screening, the molecular diagnosis can
      be provided for dystrophin, DAG, mitochondrial DNA, actin and desmin gene
      defects.

PMID- 10904834
TI  - Mitochondrial DNA deletions in cardiomyopathies.
AB  - Structural changes in the mitochondrial DNA (mtDNA) have been implicated in the
      pathogenesis of a number of diseases. In this study we report on deletions in the
      mtDNA of patients with dilated cardiomyopathy (DCM) and post mortem control
      samples. Total DNA was extracted from left ventricular tissue and nearly the
      whole mtDNA was amplified using the long PCR technique. For quantitative analysis
      of the PCR-products with mtDNA deletions the fragments were scanned by a laser
      densitometer. With the method of long PCR we could detect wild-type and deleted
      mtDNA in 1 reaction. A total of 14 different deletions ranging from 3.3 to 12.6
      kb could be detected. The highest rate of deleted as compared to wild-type mtDNA
      was 12% in 1 control and 9% in a patient with dilated cardiomyopathy. The number
      of mitochondrial deletions increase with age in the control group. Additional
      deletions appear sooner in cardiomyopathic hearts than in control hearts. With
      regard to the low quantity of the deleted mtDNA and the cumulative nature of
      these deletions by ageing, we conclude that they may be relevant in individual
      cases only. A general pathogenic effect on the development of dilated
      cardiomyopathy is less likely. The mutations may be a sign of increasing stress
      to the heart, however, thus promoting consecutive damage of mtDNA by initiating a
      vicious circle.

PMID- 10904835
TI  - The "final common pathway" hypothesis and inherited cardiovascular disease. The
      role of cytoskeletal proteins in dilated cardiomyopathy.
AB  - The genetic basis of a number of inherited cardiovascular diseases has been
      elucidated over the last few years, including the long QT syndromes, hypertrophic
      cardiomyopathy and dilated cardiomyopathy. While genetic heterogeneity has been
      demonstrated in most of these diseases, a pattern has emerged, specifically that
      genes encoding proteins with similar functions or involved in the same pathway
      are responsible for a particular disease or syndrome. Based on this observation
      we proposed the "final common pathway" hypothesis. In the case of the
      arrhythmogenic disorders, the long QT syndromes and Brugada syndrome, mutations
      have been described in a number of ion channel proteins, including cardiac
      potassium (KVLQT1, HERG and minK) and sodium (SCN5A) channels. Thus, using the
      "final common pathway" hypothesis we have proposed these diseases to be "ion
      channelopathies". Hypertrophic cardiomyopathy appears to be a disease of the
      sarcomere ("sarcomyopathy") since all the disease-causing mutations have been
      identified in the gene encoding many of the sarcomeric proteins, including beta
      myosin heavy chain, alpha-tropomyosin, troponin I and troponin T, as well as in
      actin, close to the beta-myosin heavy chain binding site. The genes responsible
      for familial dilated cardiomyopathy have been less well characterized. For X
      linked dilated cardiomyopathy, mutations in the dystrophin and G4.5 genes have
      been reported. In addition, mutations in actin (close to the dystrophin binding
      domain) and desmin, a component of the intermediate filaments, have been
      reported. However, the genes at a further 6 loci associated with autosomal
      dominant dilated cardiomyopathy (associated with conduction disease in 2 cases)
      remain unidentified. Due to the mutations in dystrophin, actin and desmin, we
      have proposed that dilated cardiomyopathy is a "cytoskeletalopathy", and we are
      currently investigating the involvement of these genes in patients.

PMID- 10904836
TI  - The myocardial expression of the adenine nucleotide translocator isoforms is
      specifically altered in dilated cardiomyopathy.
AB  - The adenine nucleotide translocator (ANT), the only mitochondrial carrier for ADP
      and ATP, combines mitochondrial energy-producing and cytosolic energy-consuming
      processes. The ANT function was observed to be impaired in explanted heart tissue
      from patients with dilated cardiomyopathy (DCM). In order to clarify whether an
      altered ANT isoform composition might be responsible for the restricted ANT
      function, we analyzed the ANT isoform expression pattern in the myocardium of
      patients suffering from dilated cardiomyopathy. The ANT isoform mRNA pattern was
      analyzed in explanted hearts from patients with dilated cardiomyopathy (n = 29),
      ischemic (n = 22) and valvular cardiomyopathy (n = 7) using the polymerase chain
      reaction technique. Myocardium from 12 subjects without heart disease was used as
      control. In addition, right ventricular biopsies from 47 patients with dilated
      cardiomyopathy who underwent cardiac catheterization were tested. A shift in the
      ANT isoform transcription profile was found in heart tissue from patients with
      dilated cardiomyopathy, but not in those from patients with ischemic or valvular
      cardiomyopathy. The shift was characterized by an increase in the ANT1 mRNA
      percentage, a decrease in ANT2 and an unchanged ANT3 proportion. Both ventricles
      and the septum were affected by the shift. The alteration was also found in
      endomyocardial specimens taken from patients with ongoing dilated cardiomyopathy.
      An alteration in the ANT isoform pattern was found to be specific for dilated
      cardiomyopathy. It is not a general phenomenon of end-stage heart failure, but
      occurs already before the heart is finally damaged. Therefore, an altered ANT
      isoform expression appears to be a feature of a dilated cardiomyopathy-specific
      gene program.

PMID- 10904837
TI  - Cardiac rhythm and conduction disturbances: what is the role of autoimmune
      mechanisms?
AB  - The immunopathogenesis of cardiac rhythm and conduction disorders has been
      underestimated. Therefore, the aim of this review is to analyze the current data
      and controversial issues in this area. The incidence of autoantibodies to human
      conducting tissue has been analyzed in sick sinus syndrome, bradyarrhythmia, and
      hypersensitive carotid sinus syndrome. Patients with anti-sinus node antibodies
      (ASNab) have a 10-fold higher risk of developing sick sinus syndrome, compared to
      age-matched controls. The risk of acquiring an atrioventricular block was up to 3
      fold in patients with anti-atrioventricular node antibodies (AAVNab) in
      comparison to controls. The incidence of anti His antibodies (AHISab) was low
      both in patients and controls. Anti-cardiac Purkinje cell antibodies (ACPCab)
      seemed to be an epiphenomenon and not a pathogenetic marker of conduction
      disorders. In congenital heart block association with HLA-B27 and HLA-DR3 is a
      possible prerequisite in the pathophysiology of the disease, although
      transplacental passage of various antibodies and immune complexes is widely
      recognized. The main autoantibodies detected both in children with congenital
      heart block and their mothers are anti-Ro/SS-A and anti-La/SS-B antibodies. The
      cross-reactivity of laminin with anti-La antibodies could be important in the
      initiation of the autoimmune process. Autoantibodies against adrenoceptors and
      muscarinic cholinergic receptors of neonatal heart and human endogenous
      retrovirus-3 expressed in fetal cardiac tissue could also play a role in the
      pathogenesis of the congenital heart block. Of note, apoptosis could be one of
      the possible mechanisms of the progression of the congenital conduction
      disturbances to the complete heart block. In addition, evidence is compiling that
      cellular activation and cellular cytotoxicity specific for a given target tissue
      appears to be at least equally important in the pathogenesis of the disease as
      the humoral response. In conclusion, the immunopathogenesis of certain cardiac
      rhythm and conduction disorders is well established in sick sinus syndrome,
      congenital heart block, and connective tissue diseases. ASNab, AAVNab, anti-Ro/SS
      A, and anti-La/SS-B antibodies can be regarded as diagnostic and prognostic
      markers.

PMID- 10904838
TI  - Prediction of major arrhythmic events and sudden cardiac death in dilated
      cardiomyopathy. The Marburg Cardiomyopathy Study design and description of
      baseline clinical characteristics.
AB  - The Marburg Cardiomyopathy Study (MACAS) is a prospective observational study
      designed to determine the value of the following potential non-invasive
      arrhythmia risk predictors in more than 200 patients with idiopathic dilated
      cardiomyopathy (IDC) over a 5-year follow-up period: New York Heart Association
      functional class, left ventricular end-diastolic diameter and ejection fraction,
      left bundle branch block and atrial fibrillation on ECG, QTc and JTc-dispersion
      on 12-lead ECG, abnormal time-domain analysis and spectral turbulence analysis of
      the signal-averaged ECG, ventricular arrhythmias and heart-rate variability on 24
      hour Holter ECG, baroreflex sensitivity, and microvolt T wave alternans during
      exercise. This report describes the rationale of MACAS as well as the clinical
      characteristics of the first 236 patients enrolled between March 1996 and October
      1999. The prognostic significance of the potential arrhythmia risk predictors in
      MACAS will be determined by multivariate Cox analysis at the end of 5-year follow
      up. Primary endpoints are total mortality and major arrhythmic events defined as
      sustained ventricular tachycardia, ventricular fibrillation or sudden cardiac
      death. The results of MACAS will have important implications for the design of
      future studies evaluating the role of prophylactic defibrillator therapy in
      idiopathic dilated cardiomyopathy.

PMID- 10904839
TI  - Definition of inflammatory cardiomyopathy (myocarditis): on the way to consensus.
      A status report.
AB  - This article reviews the current state of consensus reached for the diagnosis of
      myocarditis and dilated cardiomyopathy on the basis of conventional
      histopathological and immunohistochemical methods for inflammatory infiltrates in
      addition to molecular biological methods for persistence of viral genome in
      endomyocardial biopsies. Additionally, a brief overview is presented stating the
      current knowledge on effector mechanisms of the immune system in myocarditis and
      dilated cardiomyopathy.

PMID- 10904840
TI  - Pathology and pathogenesis of arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy is a primary heart muscle disease
      characterized by progressive myocardial atrophy of the right ventricle, with
      transmural fatty or fibrofatty replacement, either segmental or diffuse,
      accounting for electrical instability at risk of life-threatening ventricular
      arrhythmias. It was recently included among cardiomyopathies in the revised WHO
      classification. The disease was found to be a major cause of sudden death in the
      young and in athletes of the Veneto Region, Italy. A familial occurrence with
      autosomic dominant inheritance was then discovered with a prevalence estimated to
      be 6/10,000 inhabitants and 5 loci have been identified by linkage analysis so
      far, 2 mapping to chromosome 14 and to chromosome 1, 2 and 3 one each. A
      recessive form associated with palmoplantar keratosis has also been reported,
      mapping to chromosome 17. Nonetheless, the specific gene defects as well as the
      defective coded proteins have not yet been identified. At gross examination, the
      right side of the heart appears yellowish or whitish as to suggest a fatty or
      fibrofatty infiltration of the underlying myocardium; the myocardial loss
      frequently accounts for a parchment like, translucent look of the right
      ventricular free wall. Aneurysms of the right ventricular free wall, whether
      single or multiple, were reported in about 50% of cases in a recent pathologic
      investigation, and are considered a pathognomonic feature of arrhythmogenic right
      ventricular cardiomyopathy; they are typically located in the inferior,
      diaphragmatic wall, underneath the posterior leaflet of the tricuspid valve, as
      well as in the infundibulum and at the apex. Right ventricular enlargement,
      whether mild, moderate or severe, is a constant feature. Involvement of the left
      ventricle has been reported in almost 50% of cases. At histology, the pathologic
      process generally starts from the subepicardium and extends to the endocardium in
      a wave-front phenomenon. The residual, spared myocytes are located within the
      subendocardial trabeculae and few myocardial fascicles are scattered throughout
      the fibrofatty tissue. All stages of myocardial injury and repair are
      recognizable: acute cell death with sarcolysis and inflammatory infiltrates;
      subacute damage with "active fibrosis", including dying myocytes, lymphocytes and
      macrophages, or otherwise adipocytes replacing vanished myocytes; and,
      eventually, chronic stage with fibrous tissue and adipocytes surrounding residual
      surviving myocytes. Both the etiology and pathogenesis of arrhythmogenic right
      ventricular cardiomyopathy are still unknown. In particular, the mechanisms
      leading to progressive loss of myocardium and fibrofatty replacement are
      speculative. According to the frequent finding of inflammatory infiltrates at
      histology, an inflammatory theory has been advanced and infective, toxic or
      immune mechanisms have been investigated. Recently, apoptosis has been documented
      both in autoptic and bioptic material, suggesting that recurrent bouts of
      apoptosis may account for progressive atrophy of the myocardium which is then
      replaced by fibrofatty tissue. Apoptosis may be triggered by T-lymphocytes.

PMID- 10904841
TI  - Molecular pathology and structural features of enteroviral replication. Toward
      understanding the pathogenesis of viral heart disease.
AB  - Enteroviruses of the Picornaviridae and primarily coxsackieviruses of group B
      (CVB) can be detected in humans and various experimental murine models of acute
      myocarditis and chronic heart muscle diseases indicating enterovirus persistence
      in the myocardium. Persistent myocardial infection is characterized by restricted
      viral replication and gene expression in myocytes capable of sustaining chronic
      inflammation. Viral cytotoxicity was found to be crucial for organ pathology both
      during acute and persistent infection. In-situ hybridization experiments at the
      cellular and subcellular level have demonstrated that virus replication is
      associated with severe structural changes of the cardiomyocyte cytoarchitecture
      at any stage of the disease. In tissue culture experiments and transgenic mice,
      it was shown that restricted replication and gene expression of the virus are
      capable of inducing myocytopathic effects. Investigations at the molecular level
      revealed that interference of coxsackievirus replication with the cellular
      metabolism is mediated by cleavage of host cell proteins by virus-encoded
      proteinases. Notably, there is also evidence that enteroviruses are able to
      activate specific cellular signal transduction pathways in the course of
      infection, thus promoting enteroviral replication. In summary, these data
      indicate that mutual influences of virus replication and subsequent modifications
      of the host cell metabolism are crucial for cardiac injury and dysfunction during
      acute and chronic disease.

PMID- 10904842
TI  - Prevalence of viral genome in endomyocardial biopsies from patients with
      inflammatory heart muscle disease.
AB  - In the report of the 1995 World Health Federation/International Society and
      Federation of Cardiology (WHF/ISFC) Task Force on the Definition and
      Classification of Cardiomyopathies, the definition of heart muscle diseases was
      updated. Idiopathic, autoimmune, and infectious forms of inflammatory
      cardiomyopathy are now recognized in this definition. Enteroviruses, adenoviruses
      and cytomegaloviruses are considered as main etiopathological factors in the
      pathogenesis of inflammatory heart disease. A wide range of different assays have
      been and are currently being used, either alone or in combination, to assay for
      the presence of enteroviral RNA and/or DNA of cytomegalo- and adenoviruses in
      endomyocardial biopsy and explanted heart samples. The prevalence of cardiotropic
      viruses in endomyocardial biopsies of patients with clinically suspected
      inflammatory cardiomyopathy varies widely: enteroviral genome was detected in
      endomyocardial biopsies of 3 to 53% of patients, cytomegaloviral DNA was detected
      in 3 to 40% of patients with inflammatory heart disease and adenoviruses in 3 to
      23% of the patients. This report summarizes the methods that have been used and
      the results of molecular biological investigation with polymerase chain reaction,
      which were reported by several groups over the last years. Taking this together
      it seems to be clear that the improvement of molecular biological techniques and
      the experience of people working with these methods will lead to more reliable
      results on prevalence, persistence and the diagnostic value of these
      investigations. These findings have to be taken into account in future diagnostic
      and therapeutic studies in the field of cardiomyopathies.

PMID- 10904843
TI  - Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex.
AB  - Genetic deficiency of the dystrophin-glycoprotein complex causes hereditary
      dilated cardiomyopathy. Enteroviruses can also cause cardiomyopathy and we have
      recently described a potential molecular mechanism for enterovirus-induced
      dilated cardiomyopathy. The coxsackieviral protease 2A proteolytically cleaves
      and functionally impairs dystrophin. Additionally, during infection with
      coxsackievirus B3, the dystrophin-glycoprotein complex becomes disrupted and the
      sarcolemmal integrity is lost. This review article discusses the importance of
      the dystrophin cleavage for the development of increased sarcolemmal permeability
      and potential pathways for mechanisms by which the dystrophin cleavage during
      coxsackieviral infection may contribute to dilated cardiomyopathy.

PMID- 10904844
TI  - Detection of viral and bacterial protein in endomyocardial biopsies of patients
      with inflammatory heart muscle disease?
AB  - The development of highly sensitive molecular biological methods such as in-situ
      hybridization and polymerase chain reaction (PCR) made it possible to detect
      viral/bacterial nucleic acid in human endomyocardial biopsies. However, only a
      few investigations addressed the problem of latent persistence of viral and
      bacterial genome and the detection of the corresponding proteins, which could
      have important consequences for the clinical course of the disease. The purpose
      of this study was to determine whether protein of various viruses (adenovirus,
      enterovirus, cytomegalovirus, influenza A and B virus, herpes simplex virus 1 and
      2) and bacteria (chlamydia pneumonia) can be detected in endomyocardial biopsies
      of patients with myocarditis and dilated cardiomyopathy with and without
      inflammation by use of an immunofluorescence assay and to compare the frequency
      of its detection with the results of PCR, immunohistology and serology. Thirty
      nine patients with myocarditis and dilated cardiomyopathy with and without
      inflammation were examined by a direct immunofluorescence assay using the
      endomyocardial biopsy as antigen. Each of the samples was additionally studied by
      immunohistological methods and PCR for the detection of infiltrating cells and
      the genome of cardiotropic viruses or bacteria. Fourteen of patients were
      considered to have myocarditis (group 1), 9 dilated cardiomyopathy with
      inflammation (group 2), 10 dilated cardiomyopathy (group 3), 6 to have no
      myocarditis or dilated cardiomyopathy (group 4). Using a direct
      immunofluorescence assay we could show only that 1 patient without histological
      myocarditis or dilated cardiomyopathy (group 4) was positive for influenza B and
      chlamydia pneumonia antigens in the endomyocardial biopsy. In addition we have
      determined influenza B-specific antibodies, such as IgG (marginal titer) and IgA
      (high titer) and chlamydia pneumonia-specific antibodies, such as IgG (marginal
      titer) in serum of this patient. A second patient with dilated cardiomyopathy was
      found to be positive for protein of chlamydia pneumonia, who was shown to have
      chlamydia pneumonia-specific antibodies, such as IgG (high titer) in serum. There
      was no correlation with PCR results, but good correlation with influenza B and
      chlamydia pneumonia-specific antibodies in sera of these patients. In this
      investigation we have determined viral/bacterial-specific antibodies using
      serological methods and proteins of these agents using immunoflourescence.
      Despite the detection of virus or bacteria-specific antibodies in the sera and
      detection of viral and/or bacterial protein in the biopsies of some of the
      patients viral and/or bacterial genome was not found in the biopsy. This may be
      explained by the focal character of myocarditis and sampling error, because for
      technical reasons we use different biopsies for immunohistochemical and molecular
      biological investigations.

PMID- 10904845
TI  - Enteroviral and immune mediated myocarditis in SCID mice.
AB  - Severe combined immune deficiency (SCID) mice have been used as an animal model
      to study both the direct cytopathic effect of enteroviruses on the heart in the
      absence of an effective immune system and to investigate the role of immune
      mediated processes in the pathogenesis of human myocarditis. The infection of
      SCID mice with coxsackievirus B3 resulted in severe myocarditis with very high
      titers of the virus in the myocardium and severe necrosis of myocytes. This
      direct cytopathic effect caused an impairment of the myocardial function and
      resulted in a high mortality rate of the infected animals. For the study of the
      immune mechanisms in human myocarditis, peripheral blood leukocytes of patients
      with myocarditis, having an impaired left ventricular function without viral
      persistence in the myocardium, were transferred into SCID mice. As controls
      peripheral blood leukocytes of normal donors were used. At 60 days after
      transfer, human immunoglobulines could be demonstrated in the peripheral blood of
      the SCID mice, however, human autoantibodies against the adenine nucleotide
      translocator, a myocardial autoantigen, were only present in the animals
      receiving peripheral blood leukocytes from patients with myocarditis. Cellular
      infiltrates of human leukocytes in the myocardium and an impaired left
      ventricular function were also only observed in animals reconstituted with
      peripheral blood leukocytes from patients. These effects were T cell dependent as
      shown by differential transfer. These results are of interest for the treatment
      of human myocarditis, suggesting the avoidance of an immunosuppressive therapy in
      acute or chronic myocarditis with viral persistence to prevent a direct
      cytopathic effect in the absence of an effective immune system. However, in the
      setting of a chronic, (auto-)immunological myocarditis with the proven absence of
      entero- or adenoviral sequences an immunomodulatory therapy seems to be effective
      and safe.

PMID- 10904846
TI  - The outcome of coxsackievirus B3-(CVB3-) induced myocarditis is influenced by the
      cellular immune status.
AB  - Mice develop a marked age-related susceptibility to myocardial coxsackievirus B3
      (CVB3) infections. The lesions observed in mice resemble closely those seen in
      the human disease. Experimental murine models of CVB3-induced myocarditis have
      shown that both, host and viral genetic factors, can influence susceptibility to
      the infection as well as the persistence and progression of the disease.
      Recently, we have shown that CD4 T cell-deficient MHC Class II knockout mice
      develop a strong fibrosis with virus persistence in the heart tissue and without
      production of neutralizing antibodies. To examine the role of CD4+ T cells and
      especially the role of the T helper 1 cell response for the outcome and
      pathogenesis of CVB3-induced myocarditis in more detail, 2 different mouse
      strains with identical genetic background (H-2b) were infected with CVB3-Mu/J
      (Nancy strain). Immunocompetent C57BL/6 mice and mice with targeted disruption of
      interleukin (IL-)4 gene (IL-4-/- mice) developed a severe acute myocarditis on
      day 7 post infection (p.i.). The CVB3-induced inflammation was cured until the
      21st day p.i. in hearts of C57BL/6 mice. IL-4-/- mice with insufficient T helper
      2 cell immune response developed a severe myocardial damage between day 7 and 21
      p.i. with prolonged virus persistence in the heart tissue. Therefore, we suggest
      that despite an obvious normal T helper-1 cell cytokine pattern, IL-4-/- mice are
      more susceptible to long-term heart muscle injuries after infection with CVB3.

PMID- 10904847
TI  - Hepatitis C virus and cardiomyopathy.
AB  - The importance of hepatitis C virus infection has been recently noted in patients
      with hypertrophic cardiomyopathy or dilated cardiomyopathy. In a collaborative
      research project of the Committees for the Study of Idiopathic Cardiomyopathy,
      hepatitis C virus antibody was found in 74 of 697 patients (10.6%) with
      hypertrophic cardiomyopathy and in 42 of 663 patients (6.3%) with dilated
      cardiomyopathy; these prevalences were significantly higher than that found in
      volunteer blood donors in Japan. Hepatitis C virus antibody was detected in 650
      of 11,967 patients (5.4%) seeking care in 5 academic hospitals. Various cardiac
      abnormalities were found, and arrhythmias were the most frequent. These
      observations suggest that hepatitis C virus infection is an important cause of a
      variety of otherwise unexplained heart diseases. As a collaborative research with
      National Cardiovascular Center and Juntendo University, we tried to detect
      hepatitis C virus genomes using paraffin sections of autopsied hearts. Among 106
      hearts examined, beta-actin gene was amplified in 61 hearts (52.6%). Among these,
      hepatitis C virus RNA was detected in 13 hearts (21.3%), and negative strands in
      4 hearts (6.6%). Hepatitis C virus RNA was found in 6 hearts (26.0%) with
      hypertrophic cardiomyopathy, 3 hearts (11.5%) with dilated cardiomyopathy, 4
      hearts (33.3%) with myocarditis. These hepatitis C virus RNA positive samples
      were obtained between 1979 and 1990, indicating that hepatitis C virus RNA can be
      amplified from paraffin-embedded hearts preserved for many years. More recently,
      we examined the effect of interferon on myocardial injury associated with active
      hepatitis C. As TL-201-SPECT was a more sensitive method to detect myocardial
      injury induced by hepatitis C virus than electrocardiography or echocardiography,
      we used TI-SPECT scores to evaluate the effect of interferon on myocardial
      injury. SPECT scores improved in 8 patients (53%) out of 15 patients in whom
      interferon therapy was completed. Circulating hepatitis C virus disappeared after
      interferon therapy in all 11 patients with improvement or no change, but
      hepatitis C virus genomes persisted in the blood in 2 aggravated patients.
      Although this study is preliminary, interferon therapy is a promising treatment
      for myocardial diseases caused by hepatitis C virus infection.

PMID- 10904848
TI  - Expression of inducible nitric oxide synthase in experimental viral myocarditis.
AB  - Nitric oxide (NO) is an important bioactive molecule with regulatory, cytotoxic
      or cytoprotective properties. In virus-induced myocarditis, NO mediates host
      defense mechanisms against the infection or causes cardiac dysfunctions. NO is
      synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). The
      expression of the inducible form of the nitric oxide synthase (iNOS) is regulated
      by cytokines, involved in the complex myocardial immune response to enterovirus
      infections. The present study was undertaken to characterize the role of iNOS and
      NO in the murine model of viral myocarditis induced by coxsackievirus B3 (CVB3).
      In response to CVB3 infection we investigated the time course of iNOS induction
      in correlation with cytokine mRNA expression (TNF-alpha, IL-1 alpha, IFN-gamma,
      TGF-beta) in the heart of NMRI mice by RT-PCR. Positive PCR signals for viral RNA
      were found in the acute and chronic stage of disease by seminested PCR,
      indicating the persistence of viral genome. We found distinct expression of iNOS
      at all time points (1, 2, 3, 4, 7, 14, 28, 56, 98 days post infection [p.i.]).
      Higher iNOS mRNA levels were identified between days 4 until 28 p.i. in
      comparison to day 56 and 98 p.i. using densitometric values. The mRNA of the
      inflammatory cytokines TNF-alpha, IL-1 alpha, IFN-gamma appeared at days 1, 4,
      and 7 p.i., peaked at day 7 p.i. and persisted until day 98 p.i. Similar like the
      iNOS mRNA pattern was the expression profile of TGF-beta. Using in situ
      hybridization and immunohistochemistry iNOS was localized in infiltrates,
      vascular endothelial cells, smooth muscle cells, myocytes and throughout the
      interstitial spaces between myocardial fibers in the heart sections of NMRI mice.
      Increased levels of NO were measured as total nitrate/nitrite concentration in
      the sera of mice from day 7 until day 28 p.i.

PMID- 10904849
TI  - Autoantibodies against the beta- and muscarinic receptors in cardiomyopathy.
AB  - The sera of patients with idiopathic dilated cardiomyopathy and the Chagas'
      disease contain agonist-like autoantibodies directed against the beta 1
      adrenoceptor and/or the muscarinic M2-receptor. The anti-beta 1-adrenoceptor
      antibodies could be directed against amino acid sequences of the first or second
      extracellular loop. In patients with dilated cardiomyopathy the first as well as
      the second extracellular loop was identified as an antibody epitope. In Chagas'
      disease the anti-beta 1-adrenoceptor antibody recognizes only 1 epitope on the
      second extracellular loop. The anti-beta 1-adrenoceptor antibodies acting like
      the beta-adrenergic agonist isoprenaline and exert a positive chronotropic effect
      in cultured rat cardiomyocytes. In contrast to isoprenaline the antibody caused
      no downregulation of the beta-adrenergic signal transduction cascade within 6
      hours. The anti-M2 receptor antibodies recognize in both diseases an epitope on
      the second extracellular loop. The anti-M2-receptor antibody exert a negative
      chronotropic response in cultured cardiomyocytes. This antibody induced no
      downregulation of the muscarinic M2-receptor. The negative chronotropic effect
      was unabated for 6 hours. Based on these findings it is believed that the agonist
      like autoantibodies that act against the beta 1-adrenoceptor and the muscarinic
      M2-receptor may play a role in the pathogenesis of dilated cardiomyopathy and
      Chagas' disease.

PMID- 10904850
TI  - Protective effect of bisoprolol on beta-1 adrenoceptor peptide-induced autoimmune
      myocardial damage in rabbits.
AB  - Idiopathic dilated cardiomyopathy is a severe disease of unknown etiology.
      Accumulating evidence suggests that agonist-like autoantibodies against the beta
      1 adrenoceptor in the circulation of dilated cardiomyopathy may play an important
      role. The aim of this study was to evaluate the effects of the selective beta 1
      adrenoceptor blocker, bisoprolol, on beta 1-adrenoceptor peptide induced
      autoimmune myocardial damage. In the animal model of autoimmune cardiomyopathy
      induced by active immunization of rabbits with beta 1-adrenoceptor peptide,
      bisoprolol was given at a dose of 3 mg/day throughout the study period. Our
      results showed high titer of anti-beta 1-adrenoceptor antibody in the immunized
      group throughout the study but not in the group receiving only bisoprolol. Cross
      reactivity to beta 2 adrenoceptors was observed in some of the immunized rabbits,
      but disappeared almost entirely after 6 months. As compared to the beta 1
      adrenoceptor peptide immunized group without bisoprolol treatment, bisoprolol
      treated beta 1-receptor peptide immunized group showed increase in the wall
      thickness and decreases in cavity dimension in anatomical measurements and only
      mild alterations in macro- and microscopic examinations. Thus, our study clearly
      demonstrated a beneficial effect of bisoprolol in rabbits who have developed
      autoimmune myocardial damage.

PMID- 10904851
TI  - Immune modulation by catecholamines--a potential mechanism of cytokine release in
      heart failure?
AB  - Cytokine blood levels are found to be moderately elevated in chronic heart
      failure, as a function of severity of disease. The source of these cytokines and
      the trigger mechanisms stimulating cytokine release are a matter of intense
      research. Potential players include bacterial endotoxin from intestinal
      translocation, a neurohumoral dysbalance with an enhanced sympathetic tone or an
      overspill of cytokines from the failing heart itself. We present arguments in
      favor of a direct link between the chronically enhanced sympathetic tone in heart
      failure and the clinically overt activation of the immune system, particularly
      interleukin 6 release.

PMID- 10904852
TI  - Experimental autoimmune myocarditis and its pathomechanism.
AB  - The pathomechanisms of autoimmune myocarditis are quite different from viral
      infection. In this type of myocarditis, cardiac myosin fragments, proper
      dendritic cells and autoreactive T cells are the 3 major elements in initiating
      and promoting the inflammation. The causative epitope is locating on the S2 rod
      portion of the myosin heavy chain (MHC). Through our recombinant study, the
      peptide was found to be located on the latter half of MHC residues 1070 to 1165.
      Activity of antigenicity was not different between alpha and beta chain. The
      cardiac dendritic cell presents a unique structure with large mononuclear and
      interdigitating processes. This antigen presenter is quickly activated and
      suppressed by the antigen. The autoreactive T cell is closely linked with
      cytokine production. In the initial stage of myocarditis, IL-2 and IL-12 are
      increased. According to the progression of inflammatory changes, a great amount
      of IL-1b, INF-gamma and TNF-alpha is released around the diseased tissue. At the
      same time, NO is massively produced from infiltrating macrophages. Cytokines
      secreted from inflammatory cells accelerate T cell induction from Th0 to Th1. In
      the convalescent stage, production of TGF-beta 1 and IL-10 become dominant. They
      contribute to cell induction from Th0 to Th2.

PMID- 10904853
TI  - The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases
      (ESETCID). First epidemiological results.
AB  - By including immunohistochemical parameters the WHF Task Force for the Definition
      of Acute and Chronic Myocarditis expanded the light microscopical Dallas criteria
      of myocarditis. The rapid development of new molecular biological techniques such
      as polymerase chain reaction (PCR) and in-situ hybridization has improved our
      understanding of the underlying etiological and pathophysiological mechanisms in
      inflammatory heart disease. Treatment of dilated cardiomyopathy with inflammation
      is still controversial, however. The American Myocarditis Treatment Trial could
      not demonstrate a significant difference in the improvement of ejection fraction
      between patients with active myocarditis in the cyclosporine/prednisolone treated
      group when compared to placebo. In the European Study of Epidemiology and
      Treatment of Inflammatory Heart Disease (ESETCID) patients with acute or chronic
      myocarditis are treated specifically according to the etiology of the disease.
      Patients are screened not only for infiltrating cells, but also for the presence
      of persisting viral genome (enterovirus, cytomegalovirus and adenovirus). By
      investigating endomyocardial biopsies of 3,055 patients ongoing inflammatory
      processes in the heart could be found in 17.2%. Only 182 showed a reduced
      ejection fraction below 45% fulfilling the entrance criteria for the ESETCID
      trial. These data imply that in symptomatic patients inflammatory heart muscle
      disease has to be considered regardless of left ventricular function and that
      endomyocardial biopsy can be an important tool for diagnosis. Virus could be
      detected in 11.8% (enterovirus 2.2%, cytomegalovirus 5.4%, adenovirus 4.2%).
      These first epidemiological results of this prospective randomized study
      demonstrate that viral persistence may contribute to the pathogenesis of
      inflammatory heart muscle disease, and that in chronic myocarditis viral
      persistence occurs in a smaller percentage of patients compared to previously
      published studies which were performed on highly selected patients.

PMID- 10904854
TI  - Progress toward vaccines against viruses that cause heart disease.
AB  - Of the numerous viruses that have been implicated as causes of viral inflammatory
      cardiomyopathy, only the 6 serotypes of the group B coxsackieviruses (CVB 1-6)
      and adenovirus type 2 (Ad 2) have been regularly linked to heart disease on the
      basis of both clinical investigations as well as animal models (in the case of
      the coxsackieviruses). Of these, only the coxsackieviruses offer a truly well
      characterized system for not only investigations using a small animal disease
      model (myocarditis in mice) but for studies of the virus at the molecular level
      and in cell culture systems. The pending worldwide eradication of the related
      enteroviruses, the polioviruses, will further emphasize the importance of the
      coxsackieviruses in years to come. Studies using poliovirus have shown that
      enteroviruses can be attenuated for disease to create highly successful and safe
      human vaccines. Furthermore, using recombinant DNA approaches, strains of
      polioviruses have been created that demonstrate a human enterovirus can express
      small proteins as well as foreign antigenic epitopes, thus creating multivalent
      chimeric vaccine strains of virus. Our laboratory has been exploring
      coxsackievirus 3-based vectors as models for both multivalent chimeric vaccines
      as well as expression vectors. The coxsackievirus can be successfully attenuated
      using both point mutations as well as chimeric genome technology. The
      coxsackievirus can also express intact small proteins in biologically active form
      as well as antigenic epitopes. Although it is doubtful that the marketplace will
      support the development of antiviral vaccines to combat human heart disease at
      present, the technology exists to make such vaccines a reality.

PMID- 10904855
TI  - Giant cell myocarditis: diagnosis and treatment.
AB  - Giant cell myocarditis is a rare but devastating disease that usually affects
      young otherwise healthy individuals. Associations with thymoma, inflammatory
      bowel disease, and a variety of autoimmune disorders have been reported. The rate
      of death or heart transplantation is approximately 70% at 1 year. Data from a
      Lewis rat model and from observational human studies suggest that giant cell
      myocarditis is mediated by T lymphocytes and may respond to treatment aimed at
      attenuating T cell function. Recent findings from the Giant Cell Myocarditis
      Registry, a clinical and pathologic database from 63 cases of giant cell
      myocarditis gathered from 36 medical centers, include the following: The
      sensitivity of endomyocardial biopsy for giant cell myocarditis for patients who
      undergo transplantation or autopsy is 82 to 85%. Registry subjects who received
      cyclosporine in combination with steroid, azathioprine, or muromonab-CD3 have
      prolonged transplant-free survival (12.6 months vs. 3.0 months for no
      immunosuppression). Post-transplantation survival is approximately 71% at 5 years
      despite a 25% rate of giant cell infiltration in the donor heart. To confirm and
      extend these findings, a randomized trial of immunosuppression including
      muromonab-CD3, cyclosporine, and steroids is underway.

PMID- 10904856
TI  - Aldosterone and myocardial fibrosis in heart failure.
AB  - Cardiac fibroblasts are known to have high affinity corticoid receptors for
      aldosterone and account for the accumulation of collagen within the interstitium
      of the rat myocardium in acquired and genetic hypertension. This interstitial
      fibrosis is an important determinant of pathologic hypertrophy in chronic heart
      failure. To examine the relationship between aldosterone and myocardial fibrosis,
      collagen volume fraction of the left and right ventricles were analyzed by
      videodensitometry of sirius red stained tissue in the following rat models: 2
      kidney/1 clip model of renovascular hypertension; continuous aldosterone
      administration via osmotic minipumps (0.75 microgram/hour s.c.), or in each model
      of primary and secondary hyperaldosteronism with concomitant treatment with
      either low (20 mg/kg/day) or high doses (200 mg/kg/day) of s.c. spironolactone
      for 8 weeks as well as in age matched controls. Systolic arterial pressure and
      left ventricular weight normalized to body weight were each increased with either
      model of experimental hypertension and were normalized with high-dose
      spironolactone treatment. Myocardial fibrosis induced by chronic aldosterone
      administration was comparable to renovascular hypertension and occurred in the
      pressure overloaded, hypertrophied left and in the normotensive, nonhypertrophied
      right ventricle. The competitive aldosterone receptor antagonist, spironolactone,
      was able to prevent fibrosis in both ventricles in either model of arterial
      hypertension irrespective of the development of left ventricular hypertrophy and
      hypertension. To examine whether aldosterone stimulates collagen synthesis in
      adult rat cardiac fibroblasts collagen synthesis, normalized per total protein
      synthesis, was measured by 3H-proline incorporation in cultured fibroblasts after
      24 hours incubation with aldosterone at 10(-11) to 10(-6) M concentrations, or
      with 10(-9) M aldosterone + 10(-9) M spironolactone. Under serum-free conditions,
      aldosterone was able to stimulate collagen synthesis in a dose-dependent manner
      and at concentrations (10(-9) M) which were comparable to stimulated states in
      vivo (e.g., renovascular hypertension, or chronic heart failure). At equimolar
      concentrations, spironolactone abolished the aldosterone-mediated increase in
      collagen synthesis. Thus, in-vivo and in-vitro evidence could be provided that
      the mineralocorticoid, aldosterone, plays a pivotal role in promoting myocardial
      fibrosis and that could be antagonized by its competitive receptor blocker,
      spironolactone. These cardioprotective effects of spironolactone may explain the
      prognostic value of anti-aldosterone therapy in patients with severe chronic
      heart failure evaluated in the RALES mortality trial.

PMID- 10904857
TI  - Effect of hibernation, thyroid hormones and dexamethasone on cytosolic and
      mitochondrial glycerol-3-phosphate dehydrogenase from jerboa (Jaculus
      orientalis).
AB  - Tissue distribution of the cytosolic and mitochondrial glycerol-3-phosphate
      dehydrogenase (cGPDH and mGPDH) activities in jerboa (Jaculus orientalis), a
      hibernator, shows the highest level of enzyme activity in skeletal muscle and
      brown adipose tissue, respectively. The effect of hibernation on cGPDH indicates
      an increase of activity in all tissues examined. In contrast, hibernation
      decreases mGPDH activity in all tissues, except skeletal muscle. The effect of
      thyroid hormones on GPDH activity was tissue specific: in kidneys, cGPDH activity
      doubled in euthermic jerboas treated with T4. In contrast, 6-n-propyl-2
      thiouracil treatment provokes an increase of enzyme activity in brown adipose
      tissue, liver and brain. T4 treatment leads to a 2.7-fold increase in liver mGPDH
      activity. 6-n-propyl-2-thiouracil treatment decreases mGPDH activity in the
      skeletal muscle whereas the opposite effect was observed in brain. Dexamethasone
      stimulates cGPDH in all tissues examined, except skeletal muscle and kidneys. In
      the case of mGPDH activity, this increase was observed only for brown adipose
      tissue and brain. Our results suggest that hibernation, thyroid hormones and
      dexamethasone probably play a role in the regulation of cGPDH and mGPDH
      activities in jerboa. Our findings confirm that these enzymes are involved in
      metabolic adaptation to thermal stress in Jaculus orientalis.

PMID- 10904859
TI  - Sulphide detoxification in Hediste diversicolor and Marenzelleria viridis, two
      dominant polychaete worms within the shallow coastal waters of the southern
      Baltic Sea.
AB  - The polychaete worms Marenzelleria viridis (Verrill 1873) and Hediste
      diversicolor (O.F. Muller) form the main part of the macro-zoobenthos in soft
      bottomed shallow inlets of the Baltic Sea. Due to high eutrophication within
      these waters the animals are exposed to low oxygen and high sulphide
      concentrations. Specimens of both species from a low salinity location (S 8/1000)
      were compared concerning their physiological abilities in coping with this
      hostile environment. Sulphide detoxification occurred in both polychaetes even
      during severe hypoxia with the main end-product being thiosulphate. In absence of
      sulphide nearly no end-products of anaerobic metabolism were found in the worms
      during moderate hypoxia (pO2 = 7 kPa). In presence of hydrogen sulphide,
      succinate, a sensitive indicator of anaerobic metabolism, was accumulated in
      higher amounts at low sulphide concentrations (0.3 mM) already. Oxygen
      consumption and ATP production was determined in isolated mitochondria of both
      species. Both polychaetes were able to perform enzymatic sulphide oxidation in
      the mitochondria at concentrations up to 50 microM. This process was coupled with
      oxidative phosphorylation. At least in M. viridis sulphide respiration was not
      completely inhibited by cyanide, suggesting an alternative oxidation pathway,
      which by-passes the cytochrome-c-oxidase. The two species did not differ in the
      rate of sulphide detoxification, but H. diversicolor produced about as twice as
      much ATP from mitochondrial sulphide oxidation. Differences in mitochondrial
      sulphide oxidation are probably related to the different life strategies of the
      worms.

PMID- 10904858
TI  - Vitamin B12-induced alterations in activities of alpha-glycerophosphate
      dehydrogenase and malic enzyme in brain of singi fish, Heteropneustes fossilis
      (Bloch).
AB  - Different doses of vitamin B12 (0.25, 0.5, 1, 2 and 4 micrograms/g, injected
      intraperitoneally for three consecutive days) altered the activities of
      mitochondrial-alpha-glycerophosphate dehydrogenase (alpha-GPD) and NADP-dependent
      cytosolic malic enzyme (ME) in the brain of singi fish. The alpha-GPD activity
      increased at doses of 0.5, 1, 2 and 4 micrograms/g vitamin B12. A dose of 0.5
      microgram/g vitamin B12 induced less activity than higher doses. ME activity
      increased with 1, 2 and 4 micrograms/g of vitamin B12/g. The mitochondrial and
      cytosolic protein content remained unchanged after vitamin B12 administration.
      Cycloheximide treatment inhibited the vitamin B12-induced increase in alpha-GPD
      and ME activity. Thus, vitamin B12 is involved in the induction of some enzymes
      in fish brain.

PMID- 10904860
TI  - Monoclonal antibodies to plasma high density lipoprotein (HDL) of eel (Anguilla
      japonica).
AB  - Six week-old female mice (Balb/c) injected intraperitonealy with 50 micrograms of
      eel high density lipoprotein (HDL) emulsified with equal volume of adjuvant three
      times every two weeks. Three weeks after the third injection, hyperimmunized mice
      were boosted by injection of 100 micrograms of HDL. After 5 days, the best
      responding mouse to injected HDL was sacrificed, and spleen cells were fused with
      mouse myeloma cells (Sp2/O-Ag14), and hybridomas were cultured in a selection
      medium. Monoclonal antibodies specific to apolipoprotein A-I or A-II (apoA-I or
      apoA-II) of HDL were obtained by cloning and recloning the hybridomas. Eighteen
      monoclonal antibodies specific to apoA-I and/or apoApII were isolated. Antibodies
      in the culture medium were purified by a HiTrap Protein G or an eel-HDL column.
      These purified antibodies belong to the subclass IgG1. The monoclonal antibodies
      specific to eel apoA-I and apoA-II secreted by clone 10D12 and 2G3, respectively,
      interact with serum proteins of some fish species such as red-sea bream and carp.
      The anti-eel apoA-I antibody of 10D12 did not bind to serum proteins of rat,
      rabbit, and chicken, while the anti-eel apoA-II of 2G3 antibody did.

PMID- 10904861
TI  - Characterisation of nitric oxide synthase activity in the tropical sea anemone
      Aiptasia pallida.
AB  - The presence of nitric oxide synthase (EC 1.14.23 NOS) activity is demonstrated
      in the tropical marine cnidarian Aiptasia pallida (Verrill). Enzyme activity was
      assayed by measuring the conversion of [3H]arginine to [3H]citrulline. Optimal
      NOS activity was found to require NADPH. Activity was inhibited by the
      competitive NOS inhibitor NG-methyl-L-arginine (L-NMA), but not the arginase
      inhibitors L-valine and L-ornithine. NOS activity was predominantly cytosolic,
      and was characterised by a Km for arginine of 19.05 microM and a Vmax of 2.96
      pmol/min per microgram protein. Histochemical localisation of NOS activity using
      NADPH diaphorase staining showed the enzyme to be predominantly present in the
      epidermal cells and at the extremities of the mesoglea. These results provide a
      preliminary biochemical characterisation and histochemical localisation of NOS
      activity in A. pallida, an ecologically important sentinel species in tropical
      marine ecosystems.

PMID- 10904862
TI  - Rainbow trout (Oncorhynchus mykiss) cystatin C: expression in Escherichia coli
      and properties of the recombinant protease inhibitor.
AB  - Cystatins are a superfamily of low Ki cysteine proteinase inhibitors found in
      both plants and animals. Cystatin C, a secreted molecule of this family, is of
      interest from biochemical and evolutionary points of view, and also has
      biotechnological applications. Recently we cloned and sequenced the cDNA for
      rainbow trout (Oncorhynchus mykiss) cystatin C [Li et al., 1998. Molecular
      cloning, sequence analysis and expression distribution of rainbow trout
      (Oncorhynchus mykiss) cystatin C. Comp. Biochem. Phys. B 121, 135-143]. To
      explore the relationship between protein structure and function of trout cystatin
      C, we established a bacterial system for expression of the protein. Trout
      cystatin C expressed in the cytoplasm of bacterial cells did not have detectable
      protease inhibitory activity. Activity was regained by Ni-NTA chromatography
      under denaturing conditions followed by dialysis-based refolding. Titration of
      purified cystatin C preparations with papain indicated that approximately 20% of
      the total protein had been converted to the active form after one refolding
      cycle. Expression levels were 3-5 mg/l. The protease-inhibitory properties of
      recombinant trout cystatin C were similar to those of human and chicken cystatin
      C derived from biological sources and recombinant cystatin C derived from rat and
      mouse genes. The Ki for papain was 1.2 x 10(-15) M, exhibiting the high affinity
      binding unique to this family of protease inhibitors.

PMID- 10904863
TI  - Effects of organic acids on lipid synthesis and ecdysis in Triatoma infestans
      eggs.
AB  - Medium chain fatty acids are known inhibitors of the activity of lipogenic
      enzymes at the transcriptional level. Mature Triatoma infestans eggs incorporate
      [14C]-acetate into phospholipid (PL), triacylglycerol (TG), and free fatty acid
      (FFA) fractions. In the presence of sodium octanoate (SO) or sodium
      phenylethylpropionate (PHEP), lipid synthesis is inhibited in a dose-dependent
      manner. When eggs are incubated in vivo with [14C]-acetate, the usual fatty acid
      products are largely palmitic and oleic acids. However, in the presence of SO (5
      10 mM), the elongation of [14C]-acetate units is interrupted at [14C] eight total
      carbons. Eggs incubated in vivo with [14C]-SO, accumulate most of the label in
      the FFA fraction. SO (> 0.1 mM) but not sodium hexanoate (SH), inhibits the
      activity of microsomal and cytosolic fatty acid synthetases (FAS's), measured as
      [14C]-malonyl-CoA incorporation. PHEP (1 mM) and SO (10 mM) also produce major
      alterations in egg hatching and survival of the emerged insects, after a 1 h
      immersion bioassay.

PMID- 10904864
TI  - Lipid composition of the liver oil of deep-sea sharks from the Chatham Rise, New
      Zealand.
AB  - Deep-sea sharks approach neutral buoyancy by means of a large liver that contains
      large amounts of low-density lipids, primarily squalene and diacyl glyceryl ether
      (DAGE). As an animal increases in size and matures sexually, many biochemical
      changes take place within the animal. It was hypothesized that maintenance of
      neutral buoyancy in deep-sea sharks involves fine-scale changes in the chemical
      composition of the liver oil as individual sharks grow and develop. To test this
      hypothesis, the lipid composition of liver oil for individuals of different size
      and sex of deep-sea sharks from the Chatham Rise, New Zealand was compared. The
      composition of liver oil varied within and among species. Several species
      contained large amounts of squalene and DAGE, whereas only traces of these lipids
      were present in other species. The amounts of squalene and DAGE in liver oil were
      inversely related, and squalene content tended to decrease as sharks increased in
      size. Species with high squalene levels (> 80%) in liver oil were not abundant on
      the Chatham Rise, although levels of DAGE (a lipid of increasing commercial
      interest) were elevated in many species. Maintenance of neutral buoyancy in deep
      sea sharks appears to involve changes in the composition of low-density liver
      lipids as the sharks increase in size and mature.

PMID- 10904865
TI  - Differential labelling of sphingolipids by [3H]serine and ([3H]methyl)-methionine
      in fish leukocytes.
AB  - Long chain bases are constituents of all sphingolipids and their biosynthesis is
      presumed to occur via the initial condensation of serine with palmitoyl-CoA. The
      biosynthesis of phytosphingosine, a long chain base containing three hydroxyl
      groups, has been less studied than sphingosine but is assumed to occur by
      hydroxylation of sphinganine. We report in this paper that the label from
      ([3H]methyl)-methionine is preferentially incorporated into phytosphingosine
      bases of neutral glycosphingolipids, whereas the label from [3H]serine is mainly
      incorporated into the sphingoid base of sphingomyelin. These results show that in
      fish leukocytes the biosynthesis of individual sphingoid bases and their
      downstream sphingolipid products follow different pathways of metabolism. Our
      observations suggest that in fish leukocytes the synthesis of the constitutive
      long chain bases of sphingomyelin and complex glycosphingolipids is coordinately
      regulated and may be localized in separate compartments.

PMID- 10904866
TI  - Miltpain, a cysteine proteinase, from milt of Pacific cod (Gadus macrocephalus):
      purification and characterization.
AB  - Miltpain (EC.3.4.22.-) is a cysteine proteinase that preferentially hydrolyzes
      basic proteins, previously found in the milt of chum salmon. Here we report a
      similar cysteine proteinase in the milt of the marine Pacific cod. The enzyme was
      isolated and purified 6900-fold and with an estimated mass of 63 kDa by gel
      filtration chromatography and 72 kDa by SDS/PAGE. Cod miltpain has an optimum pH
      of 6.0 for Z-Arg-Arg-MCA hydrolysis, and Km of 11.5 microM and kcat of 19.0 s-1
      with Z-Arg-Arg-MCA. It requires a thiol-inducing reagent for activation and is
      inhibited by E-64, iodoacetamide, CA-074, PCMB, NEM, TLCK, TPCK, ZPCK and o
      phenanthroline. This proteinase strongly hydrolyzes basic proteins such as
      salmine, clupeine and histone, and exhibits unique substrate specificity toward
      paired basic residues such as Lys-Arg, Arg-Arg on the substrates of P2-P1. The
      isoelectric point is 5.2 by isoelectric focusing. N-Terminal sequencing gave a
      sequence of < EVPVEVVRXYVTSAPEK. The cysteine proteinase from Pacific cod very
      closely matches the previously reported miltpain from chum salmon.

PMID- 10904867
TI  - Gastropod mollusc aliphatic alcohol oxidase: subcellular localisation and
      properties.
AB  - The digestive gland and other tissues of several species of terrestrial gastropod
      mollusc contain an aliphatic alcohol oxidase activity (EC1.1.3.13). The enzyme is
      FAD dependent, consumes oxygen and generates hydrogen peroxide and the
      corresponding aldehyde. Saturated primary alcohols are favoured as substrates
      with octanol preferred with an apparent Km of 3-4 microM. The activity is clearly
      distinguishable from previously reported molluscan aromatic alcohol oxidase
      (EC1.1.3.7) on the basis of FAD dependence, sensitivity to heat treatment and
      high salt concentration and with regard to substrate preferences. The aliphatic
      alcohol oxidase is membrane associated and most likely localised to the
      endoplasmic reticulum. Extraction of membranes with 1% Igipal solubilises the
      enzyme in active form. This enzyme is a further example of an oxidase apparently
      restricted to molluscs.

PMID- 10904868
TI  - Molecular species of collagen in the intramuscular connective tissues of the
      marine crab, Scylla serrata.
AB  - Type V like collagens are widely distributed in marine invertebrates,
      particularly crustaceans and molluscs. We have been investigating the nature of
      collagens in the muscular tissues of crustaceans. The presence of type V like
      homotrimeric collagen in prawn muscle was noted before. We report here a
      comparative analysis of collagens purified from the pepsin digest of abdominal
      and pereiopod muscle tissues of the crab, Scylla serrata. The major collagen in
      either muscle precipitated at 1.2 M NaCl at acid pH, suggestive of a type V like
      property. The homotrimeric collagen was then purified to near homogeneity by
      precipitation with 20% ammonium sulphate. Solubility characteristics and
      biochemical studies indicated the leg muscle collagens to be highly crosslinked
      and stabilised by more bound carbohydrates, as compared to the abdominal muscle
      collagen. Analysis of amino acid composition revealed a close similarity to known
      type V collagens and the leg muscle collagen was characterised by more lysine
      hydroxylation and slightly reduced glycine content. The leg muscle collagen had a
      higher denaturation temperature and intrinsic viscosity than the abdominal muscle
      collagen. Our results confirm the similarity of major crustacean muscle collagens
      to vertebrate type V collagen. Further, the relative complexity of leg muscle
      collagen, unlike the abdominal muscle collagen, correlates to the specific
      functional requirements, where the former is involved in locomotion and preying
      and the latter in normal growth and development.

PMID- 10904869
TI  - Expression and characterization of human tyrosinase from a bacterial expression
      system.
AB  - To carry out biochemical characterizations of human tyrosinase and to provide an
      unlimited source of the enzyme for further study, an expression plasmid, pHis
      Tyrosinase, which contains the entire coding sequence except the signal sequence
      of a human tyrosinase was constructed and expressed in Escherichia coli. The
      expressed enzyme was simply purified by an immobilized metal affinity
      chromatography. The recombinant enzyme had the same electrophoretic mobility as
      the native enzyme from human melanoma cell and cross-reacted with the polyclonal
      antibody raised against the native enzyme. The recombinant enzyme retained its
      catalytic function with both hydroxylating and oxidative activities. Km values
      for L-tyrosine and L-3,4-dihydroxy-phenylalanine of the recombinant enzyme were
      0.17 and 0.36 mM, respectively. The activity of the recombinant enzyme was
      optimal at pH 7.5. Glutathione notably inhibited the enzymatic activity. This
      work is a further enzymatic characterization of human tyrosinase.

PMID- 10904870
TI  - Pharmacodynamic studies (PD) of didanosine (ddI) alone and in combination with
      azidothymidine (AZT) in human T-cells; a stochastic biochemical approach to
      antiretroviral nucleoside drug combination in inhibiting HIV-reverse
      transcriptase (RT).
AB  - Didanosine (ddI) is used in the treatment of HIV-1 infection alone and in
      combination with azidothymidine (AZT). When combined with AZT, patients exhibit
      improved patterns of surrogate markers after sequential combination regimens of
      ddI and AZT compared to either drug monotherapy. We have investigated the
      biochemical mechanism(s) of this synergistic drug combination in human PBMC cells
      and in human T-cell lines sensitive and resistant to AZT due to lack of thymidine
      kinase (TK). DdI is preferentially activated to its triphosphate anabolite,
      ddATP, at 3:1 ratio in human T-lymphocytes compared to monocytes from the same
      individual. There are no apparent differences in the intracellular concentrations
      of ddATP in Jurkat/0 and Jurkat/AZT-10, an AZT resistant human T-cell line, when
      ddI is administered alone or in combination with AZT, hence there appears to be a
      case of collateral sensitivity. Intracellular increases of AZTTP concentrations
      in patient's PBMC cells have been determined clinically after AZT alone and in a
      combination regimen with ddI. A stochastic biochemical model has been developed
      that estimates the velocity of HIV-RT under uninhibited and inhibited conditions
      by the active anabolites, AZTTP and ddATP. This model provides a rational
      explanation for the greater inhibition of HIV-RT in the presence of both
      inhibitors, AZTTP and ddATP, as compared to the presence of either anabolite
      triphosphate alone. Expanding this model to describe the inhibition of HIV-RT in
      the presence of three competitive inhibitors, AZTTP, ddATP and 3TCTP demonstrated
      that the presence of these HIV-RT inhibitors resulted in an even greater
      inhibition of this viral enzyme necessary for HIV integration and replication.
      Hence, a more effective inhibition of HIV-RT enzyme is achieved by the
      combination of the three drugs, AZT, ddl and 3TC. In an effort to verify this
      model with experimental data the kinetics of HIV-RT were studied in the absence
      and after inhibition by AZTTP or ddATP alone, both AZTTP + ddATP or AZTTP + ddATP
      + 3TCTP. Treatment of HIV-RT with high concentrations of these triphosphate
      inhibitors, as high as 3Kis, inhibited this enzyme to greater than 90% of
      untreated control. However, a small percentage of residual HIV-RT, 6%, was
      uninhibited even after exposure to 3Ki concentrations of each inhibitor. These
      studies strongly suggested that: 1) AZT plus ddI or AZT plus ddI plus 3TC are
      synergistic at the active anabolite level against HIV-RT; 2) the combination of
      the three nucleoside analog drugs (AZT, ddI 3TC) is needed for more effective
      inhibition of HIV-RT; 3) that the combination of the triphosphates at
      concentrations much greater than those pharnacologically achieved in T-Cells or
      PBMC under treatment conditions did not inhibit completely HIV-RT. Hence, the
      three nucleoside HIV-RT inhibitors must be combined with other classes of
      antiviral drugs or T-cell specific inhibitor drugs.

PMID- 10904871
TI  - Prevention of induced prostate-related cancer by soy protein isolate/isoflavone
      supplemented diet in Lobund-Wistar rats.
AB  - Based on epidemiological surveys, the low incidence of clinical prostate cancer
      among aged men in Japan and China were attributed to high consumption of soybean
      derived food in which phytoestrogens have numerous anticancer mechanisms. The
      prostate model in Lobund-Wistar (L-W) rats produce high levels of testosterone
      (T). They are inherently predisposed to develop induced and spontaneous
      metastasizing adenocarcinomas, which are (T)-dependent in early stages and T
      independent in advanced stages. In the experiment reported here, 2 groups of L-W
      rats (age 2 months) were fed soy-containing diets: (a) commercial diet L-485
      (TekLad) with soy meal; or (b) a soy-free diet (L-474) in which casein was
      replaced by soy protein isolate/isoflavones (SPII). At age 3 months, all rats
      were inoculated i.v. with MNU; and 14 months later, 17/58 (29.3%) of rats on diet
      L-485 developed cancer in avg 12 months, compared to 5/50 (10%) of rats on the
      SPII diet in avg 12.1 months (P = 0.001). In the latter rats, the serum levels of
      T, and weights of testes were significantly reduced; but in the former rats,
      serum levels of T remained elevated, suggesting that soy meal in L-4,85 blocked
      the estrogenic effects of phytoestrogens.

PMID- 10904872
TI  - Characterization of a new animal model for human renal cell carcinoma.
AB  - BACKGROUND: Human renal cell carcinoma (RCC) is the most common kidney malignancy
      with significant mortality. Human tumor xenograft models are important tools for
      cancer research. MATERIALS AND METHODS: We have established and characterized a
      new animal model for human RCC using Caki-2 cells implanted into the renal
      subcapsule (RSC) of nude mice. Histology, immunocytochemistry, in situ
      hybridization and magnetic resonance imaging (MRI) were used to analyze the
      tumors. RESULTS: The implantations generated reproducible carcinomas which
      closely resemble human RCC. The tumors showed cystic-papillary structures, rich
      capillary network and fibro-septa formations. Proliferation varied from 0-5% and
      from 1-60% in cystic and solid areas, respectively. Apoptosis was less than 1%.
      Macrophages and other inflammatory cell infiltrations were detected in the
      tumors. VEGF-A and angiopoietin I were expressed in a small number of cells in
      large tumors. Tumors did not metastasize outside peritoneal cavity. Survival of
      the tumor bearing animals was 23 +/- 3 weeks. CONCLUSIONS: It is concluded that
      Caki-2 carcinomas implanted into renal subcapsule of nude mice resemble human RCC
      in several aspects and represent a good animal model for studies regarding the
      pathogenesis and treatment of human RCC.

PMID- 10904873
TI  - The signaling pathway of cardiotrophin-1 is not activated in hypertrophied
      ventricles of carnitine-deficient juvenile visceral steatosis (JVS) mice.
AB  - Cardiotrophin-1 (CT-1) is a novel cytokine which is involved in the growth and
      survival of cardiac cells. We examined whether CT-1 plays a role in the
      development of cardiac hypertrophy in carnitine-deficient juvenile visceral
      steatosis (JVS) mice. The CT-1 mRNA level was quantitatively measured by the
      competitive RT-PCR method. In contrast to other models including spontaneously
      hypertensive rats, CT-1 mRNA in the ventricles of JVS mice was comparable to the
      control at 5 days and was less than half the control value at 2 and 8 weeks when
      the ventricles of the JVS mice were highly hypertrophied. There were no
      significant differences in CT-1 mRNA levels in the lung, liver, kidney, small
      intestine and skeletal muscle between the JVS and control mice at 2 weeks. We did
      not find any difference between JVS and control mice at 2 weeks in the mRNA level
      of ventricular leukemia inhibitory factor (LIF) which binds to the same receptor
      as CT-1. Furthermore, almost no phosphorylated STAT3 (signal transducer and
      activator of transcription 3), downstream of the LIF receptor and the gp130
      signaling subunit, was observed in the ventricles of JVS and control mice. These
      data show that the CT-1 signaling pathway does not play a significant role in the
      development of cardiac hypertrophy in JVS mice. Furthermore, we could not detect
      any differences in insulin-like growth factor I and II mRNA levels. All these
      data suggest distinct differences in the mechanisms of cardiac hypertrophy
      between JVS mice and other model animals.

PMID- 10904874
TI  - Novel insights into the function of the thymic Hassall's bodies.
AB  - During thymic ontogenesis, the HBs appear when lymphopoiesis is already
      established and the cortex, medulla and the cortico-medullary junction are
      capable of conducting the positive and negative selection of T lymphocytes
      undergoing progressive maturation. The HBs are structurally organized from RE
      cells, which usually undergo hypertrophy prior to their inclusion in the outer
      cell layer of the corpuscles. The cellular microenvironment of the thymic medulla
      is composed of networks of cell types, of a variety of origins, and all of them
      may participate in the construction of growing, progressive HBs. Histochemically,
      we detected a rich content of basic non-histone proteins, PAS positive substance
      (glycogen) and acid mucopolysaccharides within the bodies. Employing the
      histological stain of Pasini and immunocytochemical methods with monoclonal
      antidodies (MoABs) AE2 and AE3, high molecular weight (56.5 to 67 kD) basic
      keratins were defined in human HBs. Employing a panel of MoABs developed against
      thymic RE cell surface antigens, we observed immunoreactivity localized to the
      outer cell layer of the HBs with MoABs TE8, TE16 and TE19, while the centrally
      located cells reacted positively with TE15 and TE19. Immunoreactivity in human
      skin, employing the TE8, TE16 and TE19 MoABs was also observed in the epidermal
      granulosa cell layer, while TE15 reacted with cells of the stratum corneum. The
      presence of endocrine, peptide secreting RE cells within the HBs was defined with
      the use of MoAB A2B5, which binds to the GQ ganglioside. The hypertrophied,
      physiologically active RE cells of the peripheral cell layer of the HBs reacted
      positively with medium to strong intensity when stained with MoABs UJ127.11,
      J1153, A2B5, 215.D11, and 275.G7. We also observed the expression of transforming
      growth factor-beta type II receptors in HBs. The recently detected expression of
      the homobox gene products B3, B4, and C6, transcription factors involved in
      developmental processes related to hematopoiesis within HBs provides further
      evidence that HBs are important functional components of the RE network of the
      thymus which provide developing thymocytes with paracrine and juxtacrine signals
      to ensure their proper functional maturation during intrathymic lymphopoiesis.
      Our transmission electronmicroscopical (TEM) studies on HBs determined the
      existence of groups of RE cells connected to one another by desmosomes. We also
      observed long cytoplasmic processes originating from medullary RE cells and
      directly contacting thymic T lymphocytes and accessory antigen presenting cells
      (macrophages, dendritic cells, interdigitating cells, Langerhans cells, etc.) by
      the use of scanning electronmicroscopy (SEM). Thus, our results indicate that the
      HBs are unique, antigenically distinct, functionally active, multicellular
      components of the nonlymphocytic, cellular micro-environment of the thymic
      medulla, and participate in the physiological activities of the prenatal and
      adult thymus.

PMID- 10904875
TI  - Immunocytochemical detection of the homeobox B3, B4, and C6 gene products within
      the human thymic cellular microenvironment.
AB  - The homeobox (HOX) was originally described as a conserved DNA motif of about 180
      base pairs. The protein domain encoded by the homeobox, the homeodomain, is thus
      about 60 amino acids long. The homeodomain is a DNA-binding domain, and many
      homeobox genes have now been shown to bind to DNA and regulate the transcription
      of other genes. Thus homeodomain proteins are basically transcription factors,
      most of which play a role in development. The homeobox genes seem to represent
      another class of oncofetal antigens involved in both normal development and
      carcinogenesis, as well as tumor progression. The expression pattern of three
      homeobox gene products (HOX-B3, HOX-B4, and HOX-C6) was examined
      immunocytochemically in human thymuses of different ages and developmental stages
      (prenatal: 16 weeks and postnatal: 3 years, 5 years, and 21 years) employing an
      indirect alkaline phosphatase conjugated antigen detection technique on formalin
      fixed, paraffin-embedded tissue sections. The immunoreactivity was located in the
      thymic RE cellular network (cortical and medullar), showing different intensity
      (+3 to +4 or 50% to 90% and over 90% in the prenatal thymic tissue and +2 to +3
      or 50% to 90% during the three different postnatal stages). Intense expression
      was identified in the thymic medulla, including very strong immunoreactivity in
      the immigrating, committed hematopoietic stem cells (HSCs) present within the
      interlobular connective tissue (ICT). Strong presence of the HOX-B3 and HOX-B4
      proteins was detected in the thymic Hassall's bodies (HBs), suggesting an
      intensive functional activity of the RE cells present within these unique
      formations within the thymic medulla. The precise role of these and other HOX
      gene products in the various steps of intrathymic T lymphopoieis should be
      elucidated through further basic molecular biological research.

PMID- 10904876
TI  - Ultrasonically induced cell damage enhanced by photofrin II: mechanism of
      sonodynamic activation.
AB  - Ultrasonically induced cell damage and active oxygen generation with photofrin II
      (PF) were compared in the same in vitro insonation setup. MATERIALS AND METHODS:
      Sarcoma 180 cells suspended in air-saturated PBS were exposed to ultrasound for
      up to 60 seconds in the presence and absence of PF. The viability was determined
      by the Trypan Blue exclusion test. Ultrasonically induced active oxygen
      generation in the presence and absence of PF in air-saturated aqueous solutions
      of 50 mM 2,2,6,6-tetramethyl-4-piperidone was detected by electron spin resonance
      (ESR) spectrum. RESULTS: Significant enhancement of the rates of both
      ultrasonically induced cell damage and nitroxide generation was demonstrated with
      20-80 micrograms/ml PF. Both rates correlated very well. The enhancement of both
      rates with PF was suppressed by 10 mM histidine. CONCLUSION: These results may
      suggest that ultrasonically generated active oxygen plays a primary role in
      ultrasonically induced cell damage in the presence of PF.

PMID- 10904878
TI  - Deuterium depletion can decrease the expression of C-myc Ha-ras and p53 gene in
      carcinogen-treated mice.
AB  - In spite of the fact that the deuterium concentration is over 10 mmol/l in all
      living organisms, its possible role has been ignored for six decades. Recent
      studies have shown that the depletion of the naturally occurring deuterium can
      result in tumour regression in mice, dogs, cats and humans. The effect of
      deuterium depletion on gene expression plays a key part in tumour development.
      The carcinogen, 7,12-dimethylbenz(alpha)anthracene (DMBA), was used to increase
      gene expression in "short term" investigations. The expression of c-myc, Ha-ras
      and p53 gene was followed in CBA/Ca sensitive inbred mice drinking tap water or
      deuterium-depleted water (DDW) after induction. By detecting the RNA expression
      48 hours after exposure to the carcinogen it was found that the expression of all
      genes investigated was inhibited in six different organs (spleen, lung, thymus,
      kidney, liver and lymph node) in the DDW-treated group. It is suggested that
      genes playing a key role in the cell cycle regulation and tumour development are
      sensitive to deuterium depletion.

PMID- 10904877
TI  - Effects of combined treatment with coffee cherry and whole-body hyperthermia on
      the growth of spontaneous mammary tumours in SHN mice.
AB  - Based on findings that free access in drinking water of the extract of coffee
      cherry (CC), the residue left after the removal of coffee beans, and whole-body
      hyperthermia (WBH) induced by far-infrared ray (FIR) can markedly inhibit the
      growth of spontaneous mammary tumours of SHN mice, the effects of the combined
      treatment with these agents were examined in this study. The significant
      inhibition of tumour growth by single treatment with either CC or WBH was not
      enhanced by their combination. Meanwhile, the body weight loss during WBH was
      significantly decreased by CC. Normal and preneoplastic growth of mammary glands
      and plasma component levels were affected little by either treatment. The
      findings confirmed the "normalization effects" of CC usually obtained with
      natural products and stress the need for prudence in the choice of any agent,
      natural or synthetic, to be applied simultaneously to increase the efficacy of
      WBH.

PMID- 10904879
TI  - Effects of naturin 2 on colony formation by hematopoietic progenitor cells in
      human umbilical cord blood mediated by induction of release of growth factors.
AB  - Naturin 2, a health drink, contains a mixture of Chinese herb plants and is a
      potent immunomodulator. It has anti-tumor effects mediated by immune system. In
      the present study, low density (LD) and purified CD34+ cells (enriched for
      hematopoietic stem [HSC] and progenitor [HPC]) from human umbilical cord blood
      (CB) were assayed for colony formation in response to Naturin 2. First, we
      examined the in vitro activity of Naturin 2 on HPC. Naturin 2 by itself
      stimulated colony formation derived from either LD or CD34+ CB cells. The
      stimulatory effect by Naturin 2 was mediated by both direct and indirect action
      on HSCs/HPCs. The indirect action is via releasing of cytokines in the 5 day
      conditioned media by LD CB cells with Naturin 2. The stimulatory activities in
      the 5 day-conditioned media (CM) could be blocked by the neutralization
      antibodies against interleukin (IL)-3, granulocyte macrophage (GM)-colony
      stimulating factor (CSF), IL-1 alpha, IL-1 beta and M-CSF. Therefore, the
      stimulatory activities detected in the media conditioned are due to the cytokines
      released in the cultures. In addition, we have also determined that addition of
      Naturin 2 to the cultures with LD or CD34+ cells stimulated by IL-3 and/or GM-CSF
      resulted in a decrease of colony formation. The inhibitory effect of Naturin 2
      was mediated, at least in part, by releasing suppressive cytokines, interferon
      (IFN)-gamma and tumor necrosis factor (TNF)-alpha, in the 3 day--CM, since
      antibodies against these two suppressive cytokines partially blocked the
      inhibitory activity. These results demonstrate that Naturin 2 has differential
      effects on hematopoiesis.

PMID- 10904880
TI  - PCNA immunostaining as a valid alternative to tritiated thymidine-autoradiography
      to detect proliferative cell fraction in transitional cell bladder carcinomas.
AB  - BACKGROUND: The thymidine labeling index (T-LI) evaluated with the
      autoradiographic technique on fresh specimens is the most objective and specific
      marker of tumor proliferative cell fraction. In this study we investigated T-LI
      and PCNA expression in 68 cases of transitional cell bladder carcinomas in order
      to evaluate whether PCNA immunostaining in paraffin sections could be a valid
      alternative to autoradiographic methods for cell kinetic detection.
      Immunohistochemistry was applied after different fixatives: usual formalin,
      neutral 4% buffered formalin and Bouin. The results revealed that only in
      buffered formalin-fixed tumor specimens, considering the most darkly stained
      cells, the PCNA-LI in all cases overlapped with T-LI. Higher values than those
      observed with autoradiography were detected in PCNA values obtained after usual
      formalin fixation whereas no or faint PCNA staining was seen in material fixed in
      Bouin. Thus, only cells with strong PCNA staining can be considered as
      significant in evaluating the proliferative activity in transitional cell bladder
      carcinoma. By using immunohistochemical methods it should thus be possible to
      overcome many of the inherent difficulties of autoradiography and likewise to
      obtain accurate and significant information on the biological aggressiveness of
      bladder tumors and consequently of patient prognosis.

PMID- 10904881
TI  - Protective effect of prostaglandins on the methotrexate induced damage of small
      intestine in rats.
AB  - Methotrexate (MTX) treatment causes the damage of the small intestine, resulting
      in malabsorption. The aim of this study was to investigate the effect of
      prostaglandins (PGs), prostaglandin E1 (PGE1) and prostaglandin I2 (PGI2)
      analogues, on the MTX-induced damage of rat small intestine by examining the
      permeability of the small intestinal epithelium. The rats were treated as
      follows: MTX (15 mg/kg/day), MTX and PGE1/PGI2 analogues (0.5 and 5
      micrograms/kg/twice a day), PGE1/PGI2 analogues alone, and sterile saline
      (control). All drugs were given orally for 5 days. The intestinal permeability of
      fluorescein isothiocyanate labeled dextran with average molecular mass 4.4 KDa
      (FD-4) was examined to evaluate the dysfunction of the small intestine by the in
      vitro everted small intestine technique. The permeation clearance of FD-4
      obtained from the in vitro experiment of the MTX-treated rats increased
      remarkably, but that of the MTX and PGE1/PGI2 analogue-treated rats was
      significantly lower than that of the MTX-treated rats. These results indicated
      that PGE1 or PGI2 analogues possibly alleviated the MTX-induced damage of the
      small intestine of rats.

PMID- 10904882
TI  - Importance of treatment of depression in assuring the most efficacious management
      of Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by pathological changes which include
      degeneration of dopaminergic neurons in the substantia nigra pars compacta
      coupled with intracytoplasmic inclusions known as Lewy bodies. Neurodegeneration
      and Lewy bodies can also be found in the locus coeruleus, nucleus basalis,
      hypothalamus, cerebral cortex, cranial nerve motor nuclei, and central and
      peripheral components of the autonomic nervous system. PD progression is
      associated with the development of dementia, autonomic dysfunction, and postural
      instability, which do not respond well to conventional therapy. Therapeutic
      efforts aimed at preventing or at least delaying PD progression by reducing the
      overload of iron and generation of ROS, correcting the zinc deficiency may be of
      great benefit. Current pharmacotherapy of PD, in addition to symptomatic L-dopa
      treatment, includes the neuroprotective strategies with dopamine agonists,
      monoamine oxidase-B inhibitors (MAO-B), glutamate antagonists, catechol O
      methyltransferase (COMT) inhibitors and other antioxidants or free radical
      scavengers. Depression, anxiety disorder and stress are all associated with PD
      and it is therefore necessary to include treatment regimens for these ailments in
      addition to the traditional pharmacotherapy for the symptoms of PD, as well as
      the neuroprotective measures noted above, in order to ensure the greatest
      possible benefit to PD patients.

PMID- 10904883
TI  - Preventive effects of sulphasalazine on colorectal carcinogenesis in mice with
      ulcerative colitis.
AB  - Sulphasalazine has been used in the treatment of ulcerative colitis and is known
      to be a prodrug and split into sulphapyridine and 5-aminosalicylic acid by
      bacteria in the colon. An increased incidence of colorectal carcinoma is known to
      occur in patients with ulcerative colitis, which displays a recurrence-remission
      cycle on colorectal mucosa, i.e., the ulceration and regeneration periods of the
      colorectal mucosa. Repeated mucosal necrosis-regeneration sequence in chronic
      ulcerative colitis induced with 3% dextran sulfate sodium led to colorectal
      carcinogenesis in azoxymethane-pretreated mice. Additive treatment with
      sulphasalazine normalized the enlarged organs, i.e. liver, spleen and kidney and
      anemia and leucocytosis induced with 3% dextran sulfate sodium resulted in the
      reduction of tumorous regions with high-grade dysplasia.

PMID- 10904884
TI  - "Return trip" metastases from the liver to the pancreas in Syrian golden
      hamsters.
AB  - In 1889, Paget suggested that metastases resulted only when "seed" (certain tumor
      cells) and "soil" (specific affinity for certain organs) were matched. We report
      here, the results of implantation of a hamster nitrosamine-induced pancreatic
      cancer tissue into the liver in six animals and the resulting metastases to the
      "primary organ". Survival time and metastatic sites at necropsy were studied.
      Tumor growth in the primary implantation site was observed in 5 out of 6 hamsters
      (83.3%) that died of cancer. Survival time ranged from 82 to 199 days. Metastases
      were found in the splenic lobe of the pancreas in all 5 (100%) successfully
      implanted animals. This homologous implantation model of "return trip" in
      metastasis may be a useful tool for further research about the process of cancer
      metastasis. Moreover, it may be useful especially in the assessment of the "seed
      and soil" hypothesis.

PMID- 10904885
TI  - Leaving Laputa: what doctors aren't taught about informed consent.

PMID- 10904886
TI  - Iatrogenic cardiopulmonary arrests in DNR patients.

PMID- 10904887
TI  - The role of the clinical ethicist in conflict resolution.

PMID- 10904888
TI  - The effect of clinical medical ethics consultation on healthcare costs.

PMID- 10904889
TI  - Residents' and patients' perspectives on informed consent in primary care
      clinics.

PMID- 10904890
TI  - Report of a study to examine the process of ethics case consultation.

PMID- 10904891
TI  - Thoughts of hastening death among hospice patients.

PMID- 10904892
TI  - Respecting the autonomy of the biologically driven.

PMID- 10904893
TI  - "The aesthetics of dementia care": some final thoughts from Tom Kitwood.

PMID- 10904894
TI  - Controlled NHBD protocol for a fully conscious person: when death is intended as
      an end in itself and it has its own end.

PMID- 10904895
TI  - Intention, action, and the dead donor rule: commentary on Spike.

PMID- 10904896
TI  - Decisions by conscious persons about controlled NHBD after death: eyes wide open.

PMID- 10904897
TI  - Meaningful life and respecting brute autonomy: commentary on Spike.

PMID- 10904898
TI  - Myelomeningocele--still a challenge for the orthopaedic paediatric surgeon.

PMID- 10904899
TI  - Results of kyphectomy with the technique of Warner and Fackler in children with
      myelodysplasia.
AB  - Pathological lumbar kyphosis occurs in approximately 8% to 20% of patients with
      myelomeningocele. During the past 4 years, nine patients with an average
      preoperative kyphosis of 152 degrees were surgically corrected. They had a short
      fusion and a long stabilization with Luque rod instrumentation using a technique
      described by Warner and Fackler (1993). The average degree of correction was 104
      degrees and, on average, 2.5 vertebrae were resected. The average surgical time
      was 225 minutes, and blood loss averaged 635 ml. We saw two complications: one
      penetration of the distal part of the rod through the sacrum after 32 months, and
      a dislocation of the rods out of the first sacral foramen after 33 months. From
      our experience, this procedure is highly demanding, but effective. It should be
      limited to patients below the weight of 30 kg.

PMID- 10904900
TI  - The effect of soft tissue release of the hips on walking in myelomeningocele.
AB  - Walking and standing capacity in myelomeningocele is highly dependent on the
      level of the neurological lesion. Deformities, mainly flexion deformities, of the
      hip can severely interfere with mobility. In a retrospective study, undertaken in
      our hospital, we evaluated the role of soft tissue release of the hip in patients
      with hip flexion contractures. A special surgical technique was performed in 55
      hips. The results show a good effect on verticalization, even if the hip joints
      cannot be extended actively. A subluxated or dislocated hip did not influence the
      final outcome. During the mean follow-up of approximately 4 years, only a slight
      recurrence of the former deformity was observed. Most of the patients obtained
      great advantage from the operation.

PMID- 10904901
TI  - Follow-up study after treatment of knee flexion contractures in spina bifida
      patients.
AB  - Knee flexion contractures in spina bifida patients are seen in all levels of
      paralysis. The majority is encountered in children with thoracolumbar lesions.
      Positional deformation, spinal reflex activity, fractures around the knee joint
      and a weak quadriceps are the main causes of the flexion deformity of the knee.
      One hundred and forty-five knee flexion contractures in 80 children have been
      treated between 1980 and 1995; 15 with unilateral contracture, 65 with bilateral
      involvement. The age at the time of correction in 38 patients with thoracolumbar
      lesions was between 24 months and 11 years (average, 7.7 years). In 42 patients
      with sacral or lumbosacral lesions, the age at the time of correction was between
      10 and 19 years (average, 16.3 years). Associated surgery was mainly carried out
      on hip flexors, adductors and triceps surae. Complete posterior release was
      practiced in thoracolumbar lesions including posterior capsulotomy and release of
      the posterior cruciate ligament. In lumbosacral lesions, the lengthened tendons
      are sutured to prevent flexor weakness in the postoperative course. Vascular and
      neurologic structures are spared. Postoperative serial casts are helpful to
      achieve full extension without vascular or skin troubles. The long-term results
      were very good in 59 patients with 106 knees, good in 16 patients with 29 knees,
      and unsatisfactory in 5 patients with 10 knees. Slow deterioration years after
      surgery can be anticipated. The main causes are lack of personal initiative to
      stand and to walk, and obesity.

PMID- 10904902
TI  - Foot deformities in adolescents and young adults with spina bifida.
AB  - Spina bifida is generally accompanied by a high incidence of foot deformities.
      The goal of management is to achieve a plantigrade foot. Deformities are related
      to the level of the lesion. With thoracic lesions, the most frequent deformity is
      an equinus lesion (55%), a club foot with mid-lumbar lesion (87%) and a calcaneal
      foot with sacral lesions (34%). No deformity was present in 56% of feet in sacral
      lesion children. Club foot surgery before the age of 2 years entails a high rate
      of recurrence (78%), necessitating redo surgery. A calcaneo-valgus deformity
      developed in 45% of ambulating patients with sacral lesions requiring operative
      stabilization of the foot. Patients with sacral lesions were almost the only ones
      who remained ambulators. Ambulation was not seen to be related to foot
      deformities in adolescents and young adults.

PMID- 10904903
TI  - Gait analysis in myelomeningocele: possibilities and applications.
AB  - Gait analysis with a fully integrated laboratory is a relatively new instrument
      in the armamentarium of the pediatric orthopedic surgeon. The introduction of it
      has been especially successful in neuromuscular pathology and, particularly, in
      cerebral palsy. In spina bifida, however, it also enhances substantially the
      possibilities of detailed analysis of the locomotion problem. It is, furthermore,
      a very useful instrument in evaluating treatment and in follow-up. With a few
      examples, this paper tries to show the possibilities and advantages of a gait
      laboratory in the evaluation of patients with ambulatory spina bifida.

PMID- 10904904
TI  - Allergic reactions to latex in myelodysplasia: a review of the literature.
AB  - Current research has identified clinically relevant allergens in natural latex.
      Children with myelodysplasia are especially considered to be at risk for the
      development of immunoglobulin E-mediated hypersensitivity, which can lead to life
      threatening intraoperative anaphylaxis. A careful medical history is mandatory to
      identify patients who might be predisposed to anaphylactic reactions. Preventive
      measures involve primarily the avoidance of latex contact at home and in
      hospitals for all patients with myelodysplasia. The effectiveness of additional
      pharmacologic prophylaxis has to be determined further.

PMID- 10904905
TI  - Musculoskeletal problems in Down Syndrome European Paediatric Orthopaedic Society
      Survey: the Israeli sample.
AB  - An Israeli sample of 475 individuals representing the full spectrum of those with
      Down syndrome in the Jewish population is presented. The sample is part of a
      European multicenter study evaluating musculoskeletal disorders. Generalized
      joint laxity was found to have significant relationships with a number of medical
      conditions (knee problems, patello-femoral instability, genu valgus, pes planus,
      heart defects, and gastrointestinal problems). Body mass index was also related
      to feet problems, vertical talus, spinal problems, genu valgum, pes planus, and
      heart problems. Yearly multidisciplinary clinical follow-up is recommended in
      persons with Down syndrome.

PMID- 10904906
TI  - Racial and geographic differences of Wiberg's angle from 400 ultrasonographic
      normal hips in Italian and Brazilian infants younger than 3 months old.
AB  - The Wiberg center edge angle (CEA) of 400 hip sonographies among 200 infants, 100
      Italians and 100 Brazilians, aged from 15 days to 90 days, whose hip joints were
      considered normal, from the ultrasonographic point of view (1a and 1b) according
      to Graf's classification were measured. For the CEA measurements in the studied
      material, the authors used their own methodology developed for this purpose,
      which is based on basic geometric concepts and applied by one graphic computer
      program. In the studied material, the statistical analysis of the results
      obtained in the measurement of the CEA showed a better conformation of the
      acetabular roof complex in the Brazilian infants compared with the Italian.

PMID- 10904908
TI  - Preoperative equinus angle and prognosis in congenital talipes equinovarus: a
      preliminary report.
AB  - This study examines the hypothesis that the preoperative, clinically determined,
      equinus angle of congenital talipes equinovarus correlates with the surgical
      outcome. Data were obtained on 30 feet from 20 patients. All the patients had
      failed to respond to conservative measures of serial strapping and/or casting,
      and underwent radical primary subtalar release. Postoperatively, the Magone,
      Turco and McKay score systems were used for evaluation with 2 years minimum
      follow-up (range, 24-60 months; average, 42 months). There was a negative
      mathematical correlation between the equinus angle and the three system scores
      (Magone, Turco and McKay). In the three systems, the Pearson correlation with the
      equinus angle was negative and statistically highly significant: Magone, r = 
      0.629, P < 0.001; Turco, r = -0.651, P < 0.001; McKay, r = -0.717, P < 0.001. The
      correlation coefficients between the scoring systems were highly significant
      demonstrating a very close relationship between the systems. Excellent category
      outcomes were associated with smaller equinus angles.

PMID- 10904907
TI  - Arthrodiatasis for chondrolysis with hinge abduction: a case report.
AB  - A 13-year-old boy with bilateral chronic slipped capital femoral epiphysis was
      referred to the Nagoya University Hospital. Chondrolysis occurred on the left
      side 3 months after a subcapital wedge osteotomy and a concavity of the femoral
      head appeared, which formed hinge abduction. Increase of the joint space and
      resolution of the hinge were achieved by arthrodiatasis. As arthrodiatasis can
      resolve hinge abduction by distraction and reduce mechanical stress, it may be
      taken into consideration as an option for diseases with hinge abduction.

PMID- 10904909
TI  - Tibialis anterior tendon transfer for residual dynamic supination deformity in
      treated club feet.
AB  - Twenty-seven previously treated club feet in 25 patients were evaluated
      retrospectively following tibialis anterior tendon transfer to the dorsum of the
      foot to correct residual dynamic supination deformity. In 11 feet, the transfer
      was combined with additional soft tissue and or bony procedures to treat other
      accompanying deformities. Electrophysiologically demonstrated peroneal weakness
      causing muscle imbalance contributed to the etiology of this dynamic deformity.
      At follow-up, none of the patients had dynamic supination deformity during
      ambulation. All showed active contraction of the transferred tibialis anterior
      tendon. There was no case of overcorrection. Functional and cosmetic results were
      assessed by parents and surgeons as being excellent. Tibialis anterior tendon
      transfer is recommended to correct residual dynamic supination deformity and to
      restore muscle balance after satisfactory correction of idiopathic club foot
      contractures.

PMID- 10904910
TI  - Consequences of a fracture through a minimally ossified apophysis of the
      olecranon.
AB  - The case of a 12-year old boy with a missed olecranon fracture after an elbow
      trauma is presented. Knowledge of the ossification patterns around the elbow is
      essential in evaluating elbow trauma in children. Certain fractures of the
      immature elbow present diagnostic difficulty, which can lead to missed or delayed
      diagnosis, with possible permanent functional loss that timely diagnosis and
      treatment might avoid. This is particularly true for those fractures running
      through unossified portions of the elbow. Such a case is described.

PMID- 10904911
TI  - Clinical practice revisited: the importance of the process.

PMID- 10904913
TI  - Managed clinical networks: a new paradigm for clinical medicine.

PMID- 10904912
TI  - The National Service Framework for coronary heart disease: the emperor's new
      clothes.

PMID- 10904914
TI  - Medical rehabilitation for people with physical and complex disabilities.

PMID- 10904915
TI  - Acute medicine: the physician's future role.

PMID- 10904916
TI  - Diabetes in old age--changing concepts in the secondary care arena.

PMID- 10904917
TI  - Hypoglycaemia unawareness: causes, consequences and treatment.

PMID- 10904918
TI  - New hypoglycaemic therapies.

PMID- 10904919
TI  - Therapeutic targets for type 2 diabetes post-UKPDS.

PMID- 10904920
TI  - Saving the diabetic foot.
AB  - Diabetic foot ulceration is both preventable and treatable. The management of
      diabetic foot disease is best achieved through implementation of local protocols
      involving the primary care team, community care and the multidisciplinary
      diabetic team. It is important that the feet the assessed as part of the overall
      assessment of a diabetic patient at any clinical presentation. The initial
      management of the acute diabetic foot may present to a general practitioner or
      general physician, and involves the urgent assessment and treatment of infection,
      foot elevation, wound debridement and, where appropriate, referral for urgent
      vascular assessment in a specialist centre.

PMID- 10904921
TI  - The NHS complaints procedure. Perceptions of a recent convener.
AB  - The purpose of the NHS complaints procedure is to investigate complaints in a way
      that is satisfactory to the complainant, while being fair to staff and learning
      any lesson for service improvement. The current complaints procedure was
      implemented on 1 April 1996. It covers complaints about primary care practices as
      well as hospital and community health services, and includes matters arising from
      clinical judgement. An evaluation of its effectiveness is being undertaken by the
      London School of Hygiene and Tropical Medicine, York University (York Health
      Economics Consortium) and Public Attitude Surveys, and a report is due after the
      end of 2000. This personal view of the complaints procedure, from the perspective
      of a trust convener, discusses recent proposals for reform from the House of
      Commons Health Committee and their relevance to the hospital physician.

PMID- 10904922
TI  - God, mammon and the physician: medicine in England before the college.
AB  - Medieval medical practice has all too often been depicted by historians as
      ineffective, overpriced and riddled with superstition. Yet the physician, who
      boasted an impressive range of academic accomplishments, exercised considerable
      influence in political, religious and cultural affairs. How was this achieved?
      The overwhelming authority of the Church, in an age of high mortality, when life
      was generally painful as well as short, helps to explain an apparent paradox. For
      the practitioner, who was often also a priest, dealt with spiritual as well as
      earthly diseases, plumbing the recesses of men's souls while he examined their
      bodies. He was a confidant and mentor, offering advice on all aspects of the
      human condition. Since physical suffering was often regarded as a consequence of
      sin, confession loomed large in treatment. Indeed, the practice of both medicine
      and surgery was regulated by canon law, which looked beyond mere physical fitness
      to the quest for eternal salvation.

PMID- 10904923
TI  - Stereotactic intracranial radiotherapy/radiosurgery has come of age.
AB  - The current, highly sophisticated, brain imaging techniques and three dimensional
      (stereotactic) mapping of intracranial targets, combined with recent developments
      in concentration of radiation therapy (x- or gamma-ray) onto these targets, have
      allowed obliterative treatment for many intracranial diseases previously the
      preserve of the neurosurgeon alone. Vascular malformations, acoustic neuroma,
      complex meningioma, pituitary adenoma and craniopharyngioma all fall into this
      category, as well as base of skull tumours. There are occasional indications for
      single (a few) cerebral metastases and possibly a highly selected role in primary
      malignant brain tumours. The subject of so-called 'radiosurgery' is an important
      and developing one and is complementary to modern neurosurgery.

PMID- 10904924
TI  - Clinical research: is the filling missing from the medical research sandwich?
AB  - Clinical research is essential for patients to benefit from the advances of
      medical science. Particularly needed are thorough and imaginative investigations
      into applied physiology, clinical observation, and patients' experience. This can
      help clinicians and their patients to distinguish between pathology and healthy
      variation, interpret diagnostic information, understand what patients want and
      gain from health care, and apply study results to individuals' problems. Clinical
      research has not grown as much as other forms of medical research, and is
      sometimes regarded as unscientific. Young academic clinicians are often persuaded
      that the only road to science leads through the laboratory. Clinical research,
      however, offers equal opportunities for original enquiry, rigour and excellence.
      The medical research sandwich will continue to provide an unbalanced diet unless
      research leaders and funders take the clinical setting more seriously.

PMID- 10904925
TI  - NTNs and all that! Will specialist registrars get a consultant post a will
      consultants have a registrar?

PMID- 10904926
TI  - Consultant post prospects in medical specialties.
AB  - Consultant post prospects for Specialist Registrars (SpRs) in all the medical
      specialties have been analysed using the databases of the Royal College of
      Physicians and the Joint Committee on Higher Medical Training (JCHMT). A 'bulge'
      in the numbers of SpRs obtaining Certificates of Completion of Specialist
      Training (CCSTs) is anticipated over the next 2-3 years, but this effect will be
      alleviated by the increasing trend to spend extra years in research or flexible
      training. There are profound differences between the specialties in the ratios of
      SpRs holding National Training Numbers (NTNs) to consultants, and in the
      proportions of female SpRs, and these factors will markedly influence consultant
      post prospects. The outlook within most specialties is favourable, but this is
      critically dependent on the rate of consultant expansion over the next few years.

PMID- 10904927
TI  - Alpha-1-antitrypsin deficiency, the serpinopathies and conformational disease.
AB  - Alpha-1-antitrypsin deficiency results from point mutations that distort the
      structure of the protein to allow a unique protein-protein interaction that we
      have termed loopsheet polymerisation. Polymers of Z alpha 1-antitrypsin
      accumulate within hepatocytes to form inclusion bodies that are associated with
      juvenile cirrhosis and hepatocellular carcinoma. The lack of circulating protein
      predisposes the Z alpha 1-antitrypsin homozygote to emphysema. This process also
      occurs in other members of the serine proteinase inhibitor (serpin) superfamily,
      antithrombin, C1-inhibitor and alpha 1-antichymotrypsin, in association with
      thrombosis, angioedema and chronic obstructive pulmonary disease, respectively,
      and we have recently shown that it underlies a novel inclusion body dementia. The
      interaction provides a useful paradigm for other 'conformational diseases' such
      as Huntington's disease, Creutzfeldt-Jakob disease and the amyloidoses.

PMID- 10904928
TI  - Recent advances in autoimmune diseases.

PMID- 10904929
TI  - Measuring the quality of care for older people: preparing for the National
      Service Framework.

PMID- 10904930
TI  - The 'learning curve' for temporary pacing: evidence that current training
      guidelines are unrealistic.

PMID- 10904931
TI  - General internal medicine and specialty medicine--time to rethink the
      relationship (July/August 1999 pp341-7)

PMID- 10904932
TI  - Measuring clinical outcome in asthma.

PMID- 10904933
TI  - Low birthweight in electoral wards: a useful health and social indicator at local
      level.
AB  - Greater use of electoral ward data is recommended for the guidance of allocation
      of resources to reduce low birthweight rates and for the monitoring of the health
      of communities. Ward data on low birthweight can be used for correlation studies
      to show the many associations of social, economic and health factors with low
      birthweight and with each other. A recent government report shows a substantial
      increase in the prevalence of disability since 1985 which is partly a consequence
      of an increase in low birthweight and of a deterioration in the nutritional
      status of an important minority of poor families who are concentrated in inner
      city wards.

PMID- 10904934
TI  - The correlation between nutrition knowledge and eating behavior in an American
      school: the role of ethnicity.
AB  - The purpose of this study was to examine the relationship between nutrition
      knowledge and eating behavior of a sample of middle school children. The
      participants were 532 students in the sixth, seventh, and eighth grades from
      Shawnee Middle School in Lima, Ohio. The students were asked to a complete a
      questionnaire (CANKAP--Comprehensive Assessment of Nutrition Knowledge,
      Attitudes, and Practices), which measured nutrition knowledge and eating
      behavior, and is reproduced here. The data were coded and computer-analyzed using
      the SAS statistical program for analysis by frequency distribution, one-way
      analysis of variance, Pearson Correlation Coefficients. Data analysis provided
      the following results: Mean nutrition knowledge scores of sixth grade students
      (68.4) were higher than mean nutrition knowledge scores of seventh and eighth
      grade students (58.5 per cent). The relationship between nutrition knowledge and
      eating behavior was insignificant for sixth grade students, but significant for
      seventh and eighth grade students. Also, "Caucasians" had higher mean knowledge
      scores than "Other" ethnic groups combined. The students demonstrated knowledge
      about the cultural and psychological aspects of nutrition. However, they were not
      able to identify the food sources of nutrients or nutrient functions, and they
      did not use a daily food guide to choose foods, although they were aware of the
      importance of milk and vegetable consumption. Knowledge about nutrition and
      healthy eating behavior appears to be weak within this group, and it would be
      beneficial to promote a nutrition curriculum for students in middle schools.

PMID- 10904935
TI  - Antinutrients and digestibility (in vitro) of soaked, dehulled and germinated
      cowpeas.
AB  - Phytic acid, polyphenols, protein and starch digestibility (in vitro) in two
      varieties, namely CS-46 and CS-88, of soaked, dehulled and germinated cowpeas
      were determined. Soaking for 12 hours, dehulling of soaked seeds and germination
      for different time periods (24, 36 and 48 h) contributed significantly in
      reducing the phytic acid and polyphenol content of cowpeas. Removal of seed coat
      (dehulling) of soaked cowpeas reduced the polyphenols by 70-71%. Soaking (12 h)
      brought about an improvement in protein and starch digestibility which further
      increased after dehulling. Progressive increase in digestibility (protein and
      starch) was noticed, with an increase in germination period. Dehulling of soaked
      seeds was most effective in reducing the polyphenolic content, and germination in
      enhancing protein and starch digestibility.

PMID- 10904936
TI  - Breast feeding practices in urban and rural health centres: impact of baby
      friendly hospital initiative in Ile-Ife, Nigeria.
AB  - The present study was carried out to assess the impact of the Baby Friendly
      Hospital Initiative (BFHI) on breast feeding practices. The variables used to
      evaluate the BFHI centre included time of initiation of breastfeeding (BF) after
      delivery, intended duration of BF, adoption of exclusive breastfeeding (EBF) in
      relation to educational status, location of health centre, and knowledge and
      practice of positioning the child at the breast. Observation, questionnaire and
      interview techniques were employed to collect the data among 217 and 214 nursing
      mothers (NMs) from Urban and Rural Health Centres. Of the 228 NMs who initiated
      BF within 30 minutes after delivery, 140 (61%) were from a designated BFHI Centre
      and 88 (39%) were from an undesignated BFHI rural health centre. There was a
      significant relationship between the practice of EBF and designation of BFHI
      centre (P = 0.0001). The higher the level of education of the NMs, the higher the
      present of NMs subscribing to EBF (P = 0.0001). The present study has also
      confirmed that EBF which was once considered to be less than 3%, has increased
      significantly to 61%. The success was not unconnected with the inauguration of
      BFHI. The BFHI is recording huge success in the urban area but the impact is
      still to be felt in the rural areas.

PMID- 10904937
TI  - The significance of water in sport and weight control.
AB  - Intake of food and drink during exercise can be effective in enhancing
      performance, in so far as it prevents or ameliorates exercise-induced changes to
      body homeostasis. Loss of body fluids containing water and electrolytes during
      exercise is mostly by sweating. Sweat rates during a sporting event or activity
      will vary according to a number of factors, including the size of the athlete and
      his or her degree of acclimatization, the intensity of exercise, environmental
      conditions and the clothing worn. The mismatch of fluid intake and fluid losses
      may lead to a body water deficit. It has generally been considered that decreases
      in performance become apparent when hypohydration exceeds 2% of body weight; that
      performance decrements become substantial when fluid losses exceed 5% of body
      weight; and that when fluid losses approach 6-10% of body weight, heat stroke and
      heat exhaustion become life-threatening. Hypohydration also affects mental
      functioning. Therefore, the effect of hypohydration on real-life sport may be
      greater than that shown in laboratory studies of physiological performance.

PMID- 10904938
TI  - Effect of Wainan Rogo on body weight and plasma glucose in Wistar rats.
AB  - Wainan Rogo (WR) is a deep-fat fried dough made from grated fresh cassava. It was
      found in a cross sectional case-control study to have a risk factor 3.2 times
      higher in diabetic than non diabetic indigenes of Borno State of Nigeria. This
      study examines the chemical composition, and effects of WR on body weight and
      blood glucose in Wistar rats. The study found a higher fat and lower protein
      composition of the WR diet, and found a higher plasma glucose in the WR fed rats
      and a more significant weight loss in this group than in the control (CF) fed
      rats. The findings of this study seem to support the high risk for diabetes
      associated with WR in the cross sectional study. The chemical composition of WR
      and its effect on body weight and blood glucose are further discussed, with a
      call for further studies of the food as a marker in the search for the
      pathophysiology of Malnutrition-Related Diabetes Mellitus (MRDM).

PMID- 10904939
TI  - Contaminated material caused Creutzfeld-Jakob disease (CJD) in some undersized
      children who were treated with growth hormone (GH).

PMID- 10904940
TI  - Localization of somatostatin receptors at the light and electron microscopial
      level by using antibodies raised against fusion proteins.
AB  - Somatostatin mediates its multiple biological effects via specific plasma
      membrane receptors belonging to the family of G-protein coupled receptors with
      seven putative membrane-spanning domains. Five somatostatin receptor subtypes
      (sst1-sst5) have been cloned in human, mouse, and rat. We have raised specific
      antibodies against the five human somatostatin receptors by using the fusion
      protein technique. DNA sequences encoding C-terminal parts of the somatostatin
      receptors were inserted into a pGEX-2T plasmid vector. E. coli bacteria were
      transformed with the recombinant plasmid and fusion proteins were expressed and
      purified using the glutathione S-transferase Gene Fusion System. The fusion
      proteins were emulsified with Freund's complete adjuvant and polyclonal
      antibodies were raised in rabbits. The antisera were tested for specificity in
      Western blot analysis of membrane preparations from cell lines expressing the
      receptors and in membrane preparations of brain tissues. The receptors were
      visualized at the light microscopical level in paraformaldehyde fixed tissue
      sections by use of biotin labelled secondary antibodies as well as by
      amplification with biotinylated tyramide. The final step in the
      immunohistochemical visualization of the receptors was done by both peroxidase
      labelled streptavidin/biotin and different fluorophores. At the electron
      microscopical level, some of the receptors could be visualized in tissues fixed
      with a combination of paraformaldehyde and low concentrations of glutaraldehyde.
      In the hamster brain, sst2 receptors labelling was observed in both neuronal
      processes and perikarya. The staining was present in neo-, and allocortical areas
      of the forebrain, the hypothalamus, brain stem, and spinal cord. In the rat and
      human, sst1 receptor was shown to be an auto receptor on somatostatinergic
      neurons located in the hypothalamus. In the retina both sst1 and sst2 receptors
      were present. sst1 receptors were confined to amacrine cells, few ganglionic
      cells, and Muller cell-end feet. sst2 receptors were more widespread than the
      sst1 receptors. sst2-immunoreactivity was present in dopaminergic amacrine cells,
      the Muller cell-end feet, and in the inner segments of the cone photoreceptors.
      Thus, the availability of subtype specific antibodies against the five
      somatostatin receptors makes it possible to identify the receptors involved in
      the multiple somatostatinergic system in the body.

PMID- 10904942
TI  - [The efficacy of neurophysiological examination in the diagnosis of carpal tunnel
      syndrome].
AB  - INTRODUCTION: The validity of studies of nerve conduction in the diagnosis of
      carpal tunnel syndrome has been sufficiently demonstrated, especially the speed
      of nerve conduction across the carpus. It has also been proved that the result of
      the test varies according to its use. OBJECTIVE: This study is to evaluate the
      result of the study of nerve conduction in the diagnosis of carpal tunnel
      syndrome in a population attending a clinical neurophysiology department for
      examination of suspected neuro-muscular disorders of the upper limit. PATIENTS
      AND METHODS: We selected the cut-off points of the values of speed of nerve
      conduction along the median nerve from the thumb (E1) and palm of the hand (E2).
      Those showing the best sensitivity and specificity were chosen (53 and 51 m/s
      respectively). We assessed the pre-test and post-test probability to measure the
      examination result. There was little contribution from this examination to the
      diagnosis of carpal tunnel syndrome in this population. CONCLUSIONS: The high pre
      test probability of a disorder is a cause of low efficacy of the examination done
      to confirm this and the opposite occurs when it is done to rule it out. The
      efficacy of an examination should be measured in the setting in which it is used
      since this does not depend only on its intrinsic characteristics but also on how
      it is used.

PMID- 10904941
TI  - [Molecular studies in Cuban patients with progressive external ophthalmoplegia].
AB  - INTRODUCTION: The mitochondria, subcellular organelles which possess their own
      DNA (mtDNA), produce most of the energy, in the form of ATP, which is necessary
      for life. This mtDNA may have diverse molecular defects which have been
      associated with a great variety of clinical syndromes. Deletions in mtDNA are one
      of the common mutations in patients with mitochondrial myopathies, which in the
      great majority present with the common symptom of progressive external
      ophthalmoplegia. In this study we report our findings in eight Cuban families
      with suspected mitochondrial disease. OBJECTIVES: To characterize these patients
      from the molecular point of view, which would allow a preliminary understanding
      of the behavior of these deletions in Cuban patients. PATIENTS AND METHODS: We
      studied nine patients from eight Cuban families in whom mitochondrial
      encephalomyopathy was suspected. We analyzed the presence of ragged red fibres,
      the enzymatic activity of the mitochondrial respiratory chain and detection of
      mtDNA mutations. We used the technique of restriction length polymorphism
      analysis for detection of deletions. RESULTS: Histochemical studies showed the
      presence of COX negative ragged red fibres in seven of the patients studied. The
      enzymatic activity of the mitochondrial respiratory chain was normal in all the
      patients. We detected four patients with single deletions of mtDNA, and one with
      multiple deletions and of the patients had the A3243G mutation. CONCLUSIONS: With
      the methods used we were able to determine the presence of a mitochondrial
      disorder in seven of the eight families studied and deletions of mtDNA were
      detected as the cause of the illness in five. The disorder was always associated
      with progressive external ophthalmoplegia and COX negative ragged red fibres.

PMID- 10904943
TI  - [Semiquantitative evaluation of cranial computerized tomography as diagnostic
      support in progressive supranuclear palsy].
AB  - INTRODUCTION AND OBJECTIVES: Different neuroimaging findings have been described
      in association with progressive supranuclear palsy (PSP), but their use as
      diagnostic support in this condition has been the subject of much discussion.
      PATIENTS AND METHODS: Three radiologists, non-specialists in neuroradiology and
      with no specific information regarding neuroimaging in Parkinson syndromes,
      analyzed (without knowing any clinical details) seven cranial CT in five patients
      diagnosed as probable PSP according to NINDS-SPSS criteria, nine with idiopathic
      Parkinson's disease, and six persons aged over 55 years who acted as controls.
      The radiologists were asked to assess 17 variables as absent, moderate or severe.
      The results were analyzed using the chi squared test for qualitative variables
      and Fisher's exact test when necessary. RESULTS: The identification of the
      variables antero-posterior and transversal atrophy of the mid-brain, atrophy of
      the pons, enlargement of the perimesencephalic cisterns and the quadrigeminal
      plate and increased size of the third ventricle were considered to be
      statistically significant in the cases of PSP as compared with other
      observations. The small number of patients did not permit the establishment of
      correlation of statistical importance between the radiological parameters and
      clinical condition. CONCLUSIONS: We present the point of view of non-specialist
      neuroimaging workers, in these patients. We found that there were six parameters
      of interest on cranial CT which permitted differentiation of cases of PSP,
      idiopathic Parkinson's disease and a control population. Four of these parameters
      did not appear to a severe degree in patients who did not have PSP. These results
      are partly comparable to those published in the literature.

PMID- 10904944
TI  - [Validation of a model for the prediction of verbal semantic fluency].
AB  - INTRODUCTION: The diagnosis of dementia requires documentation of cognitive loss
      with respect to the patient's previous level. It would therefore be very useful
      to have models available which would predict the result expected in the tests
      normally used in the diagnosis of dementia. OBJECTIVE: To validate a model for
      prediction of the results of a test of semantic verbal fluency in persons with no
      dementia. PATIENTS AND METHODS: A model for the prediction of semantic verbal
      fluency deduced from a sample of 138 persons was applied to two other independent
      samples: the first of 86 persons from the same environment as the original sample
      and a second multicentric sample of 92 persons. The validity of the model was
      evaluated by residual analysis. RESULTS: No sex differences were seen between the
      samples, but there were differences regarding the other variables, including the
      observed and predicted verbal fluency. The residuals of the samples did not
      differ from each other nor vary from zero, but were normally distributed.
      CONCLUSION: The model proposed based on sociodemographic and clinical variables
      is valid and satisfactorily predicts the verbal fluency to be expected in each
      case.

PMID- 10904945
TI  - [Behavior characterization of a model of Huntington's disease in rats, induced by
      quinolinic acid].
AB  - INTRODUCTION: Huntington's disease (HD) is a progressive neurodegenerative
      disorder, characterized by severe degeneration of basal ganglia neurons.
      Behavioral symptoms of HD include abnormal, uncontrollable and constant
      choreiform movements, impaired cognitive function and emotional disturbance.
      OBJECTIVE: In order to explore the changes of cognitive and motor functions
      induced by quinolinate lesion we realized this experiment. MATERIALS AND METHODS:
      We studied the behavior of rats with unilateral quinolinate induced lesions of
      the medial striatum. Intact 3 months old male rats (n = 23) were trained in the
      Morris Water Maze during three consecutive days, eight trials/day (acquisition),
      and before surgery they were randomly assigned either to intact or lesion groups.
      Fifteen days after the lesion the rats were tested using retention test (one
      day/four trials, with the escape platform in the same position as in acquisition
      test), on the next three days the rats were tested in the transfer test (three
      days/eight trials-day, with the platform in the new position). The Paw reaching
      test and the asymmetrical rotational behavior test in respond to amphetamine were
      also tested in these rats. RESULTS: Lesioned animals exhibited deficient
      retrieval of stored memories of visuospatial skills and impaired transfer of
      learning. In relation with motor activity the lesioned rats showed a profound
      impairment in the skill of the left forelimb for reaching food compared with its
      right forelimb as well as with the forelimb abilities of intact rats. The
      lesioned animals showed significant rotational behavior induced by amphetamine
      agonist, ipsilateral to the lesioned striatum. CONCLUSIONS: These results are
      consistent with the notion that the striatal degeneration could sufficiently
      account for the cognitive abnormalities associated with HD, and with the key role
      played by basal ganglia in enabling voluntary and postural adjustment of the
      movements.

PMID- 10904946
TI  - [Aminoglycoside antibiotics neomycin and kanamycin inhibit the increase of of
      pyroglutamyl aminopeptidase activity by depolarizing synaptosomes of the frontal
      cortex of the rate].
AB  - INTRODUCTION: Thyrotrophin releasing hormone (TRH) has emerging in the last few
      years as a neuropeptide with important functions, not only as neurohormone into
      the hypothalamus-pituitary axis, but as neurotransmitter in several areas of the
      nervous system. Although little is known about its extra-endocrine functions, TRH
      has been related with several types of psychiatric disorders. Pyroglutamyl
      aminopeptidase (pGluAP) is the enzyme involved in the degradation of TRH.
      OBJECTIVES: The present research studies the levels of pGluAP activity under
      basal (resting) and KCl-stimulated (depolarized) conditions. The role of
      intracellular free calcium homeostasis, by means of the aminoglycoside
      antibiotics neomycin and kanamycin as voltage-dependent calcium channels
      blockers, is also studied. MATERIAL AND METHODS: Both pGluAP activity and
      intracellular free calcium concentration were analyzed in synaptosomes obtained
      from the frontal cortex of rats. Synaptosomes were incubated in artificial
      cerebrospinal fluid, under basal (resting) or KCl-stimulated (depolarized)
      conditions, with of without neomycin or kanamycin at different concentrations.
      RESULTS: Depolarization increases significantly pGluAP activity, which is
      completely abolished by neomycin and kanamycin at the lower concentrations used.
      On the contrary, aminoglycoside antibiotics do not block completely the increase
      on intracellular free calcium concentration induced by depolarization. Under
      basal conditions, no changes were found on pGluAP activity nor intracellular free
      calcium. CONCLUSIONS: pGluAP activity could regulate the
      neurotransmitter/neuromodulatory functions of TRH trough intracellular free
      calcium movements through aminoglycoside-sensitive voltage-dependent calcium
      channels. A role for inositol 4,5-bisphosphate breakdown products is also
      suggested.

PMID- 10904947
TI  - [The prevalence of dementias in a rural area. A study in Girona].
AB  - OBJECTIVES: To know the prevalence of dementia and its subtypes in our area.
      PATIENTS AND METHODS: Epidemiological study, door-to-door, double phase, in which
      all non-institutionalized subjects from 8 rural villages aged 70 and more were
      selected. The general physicians and nurses, previously trained, administered the
      Mini Cognitive Examination (MCE) in the first phase. All subjects to whom cannot
      been administered MCE due to illness or sensorial deficit, all subjects under the
      cut-off point and a similar number of subjects randomized among the ones over the
      cut-off point, get through the second phase in which a clinical psychologist and
      a neurological trained physician administered the Cambridge Mental Disorders of
      the Elderly Examination (CAMDEX). All diagnosis were done under CAMDEX criteria.
      RESULTS: A total of 1,460 subjects participated. The prevalence of dementia was
      16.3% (14.4-18.2). The dementia Alzheimer type ratio was 40.76% (34.5-47), the
      vascular dementia was 38.24% (32.1-44.4), the mixed dementia was 11.7% (7.7-15.8)
      and the secondary dementia was 9.2% (5.5-12.9%). The logistic regression confirms
      that age and female sex are dementia risk factor. CONCLUSION: In our geographical
      area a very high prevalence of dementia is found.

PMID- 10904948
TI  - [Becker's myotonia in Peru].
AB  - INTRODUCTION: The word myotonia was used for the first time by Strumpell in 1891.
      Diseases associated with this symptom are called myotonias. They are classified
      on the basis of their clinical features in: congenita myotonia, paramyotonia
      congenita, myotonic dystrophy and Schwartz-Jampel syndrome. Becker's myotonia is
      a generalized congenita nondystrophic myotonia transmitted as an autosomal
      recessive trait and caused by allelic mutation of the gene encoding the chloride
      channel CLC-1 of the skeletal muscle fiber surface membrane, localized on
      chromosome 7q35. At the present time, nondystrophic myotonias are referred as
      channelopathies. CLINICAL CASE: We describe a case of generalized myotonia in a
      Peruvian young male, descending of Europeans, without familial history.
      CONCLUSIONS: We discuss his clinical symptoms, laboratory and electrophysiologic
      findings, differential diagnosis, and response to the treatment with
      carbamazepine. We report the first case of Becker's myotonia in Peru.

PMID- 10904950
TI  - [Nonconvulsive status epilepticus of frontal origin. A case report].
AB  - INTRODUCTION: Nonconvulsive status epilepticus (NCSE) of frontal origin is a form
      of partial status epilepticus which has rarely been well-documented. The
      inespecificity of the symptoms contribute frequently to its misinterpretation
      being the EEG the most useful tool to make an accurate diagnosis. CLINICAL CASE:
      We report a 53-year-old woman who suffered from two generalized tonic-clonic
      seizures secondary to a left frontal hematoma in 1994. Onset of treatment with
      carbamazepine was followed by a complete control of seizures. After remaining
      seizure-free during four years, antiepileptic therapy was discontinued. By June
      1999, she presented with a prolonged confusional state having a generalized tonic
      clonic seizure at the emergency room. At that moment, a computed tomography (CT)
      scan was normal. Generalized seizures were controlled with phenytoin, however,
      the patient remained confused having occasionally episodes of turning of the head
      and eyes to the right side. Ictal EEG examination showed recurrent bilateral
      frontopolar, frontocentral and frontotemporal epileptiform discharges with a left
      frontal focal onset. The diagnosis of NCSE of frontal origin was made. Despite
      several anticonvulsant combinations, confusional state remained unchanged and she
      was transferred to the intensive care unit for sedation with propofol and
      mydazolam. On the following days, she experienced a marked improvement and EEG
      showed a few frontal spikes and sharp waves but without evidence of
      electrographic status epilepticus. The patient was finally discharged and remains
      seizure-free on phenytoin therapy. CONCLUSIONS: Our clinical and EEG findings are
      in keeping with the diagnosis of NCSE of frontal origin. A severe confusional
      state was the most prominent symptom and EEG was essential for the diagnosis.

PMID- 10904949
TI  - [Central pontine myelinolysis and pregnancy: a case report and review of
      literature].
AB  - INTRODUCTION: The 'rapid' correction of hyponatremia, itself a dangerous
      condition, is dangerous to the patient involved. There is an association between
      the 'rapid' correction of plasma sodium and the osmotic demyelination syndrome,
      characterized by the loss of myelin in the pontine neurons, and in extra-pontine
      sites such as the internal capsule, basal ganglia, cerebellum and cerebrum.
      Although cases of hyponatremia during pregnancy have been described, it has
      rarely been possible to demonstrate the condition, by imaging techniques or
      autopsy, showing demyelination lesions of the cerebrum. We report the case of a
      pregnant patient who developed this complication and had an interesting response
      to levodopa. CLINICAL CASE: A 27 year old woman had a history of progressive
      generalized muscle weakness for the previous six days. She had recently been
      discharged after receiving treatment for hyperemesis gravidarum. Imaging studies
      showed pontine and extrapontine myelinolysis. She was treated with levodopa which
      improved her extrapyramidal symptoms. CONCLUSIONS: Hyponatremia is the most
      commonly observed electrolyte disorder in the hospital population. The classical
      symptoms of myelinolysis are spastic quadriparesia and pseudobulbar paralysis,
      which reflect damage to corticospinal and corticobular paths. Serious symptomatic
      hyponatremia is a medical emergency which should be managed by specially trained
      personnel, since the treatment is as dangerous as the condition itself. More
      investigations are necessary to identify the precise risk factors and the
      mechanism by which an increase in sodium causes damage to myelin.

PMID- 10904951
TI  - [Agitation in head injury. II. Treatment with antidepressant, sympathomimetic,
      beta blocker , dopaminergic and other drugs].
AB  - OBJECTIVE: To review the literature of the past 20 years, using the articles
      indexed in MEDLINE, on the drug treatment of agitation in traumatic head injury.
      DEVELOPMENT: The treatment of agitation in traumatic head injury should be based
      on well-designed, randomised, placebo-controlled studies which justify any
      particular decision regarding drug use. However, care of the agitated traumatic
      head injury patient is based on the management of other related disorders, on the
      response of similar patient populations and clinical experience based on
      empirical observation. Amongst the drugs available, carbamazepine is the most
      widely used for post-traumatic agitation, followed by antidepressants and as a
      third option propranolol. We discuss other drugs which are used less frequently
      in post-traumatic agitation. CONCLUSIONS: Many drugs are used and there is little
      agreement on the subject. However, with regard to certain characteristics of the
      agitation, different pharmacological treatments may be recommended.

PMID- 10904952
TI  - [Peripheral facial paralysis: etiology, diagnosis and treatment].
AB  - OBJECTIVE: Peripheral facial paralysis is one of the commonest mononeuropathies.
      The frequency of idiopathic peripheral paralysis or Bell's palsy varies between
      62% and 93% of all cases, with an incidence of between 14 and 25 cases per
      100,000 inhabitants per year. However, in spite of its relative frequency in the
      population, there is still no definite unanimously agreed strategy currently used
      by neurologists. Although its course is relatively benign, up to 16% of the
      patients show moderate or severe sequelae according to follow-up data in 1,011
      untreated patients. In this article we review the aetiology, diagnostic methods
      and therapeutical strategies at the present time. DEVELOPMENT: The topographic
      diagnosis of the lesion is based on the symptoms associated with the paralysis.
      The neurophysiological studies (trigeminofacial reflection and electroneurogram),
      usually done after the first week are prognoses that permit differentiation of
      the degree of the lesion (neuropraxis, axonotmesis or neurotmesis). In spite of
      recent trials with combined therapy (acyclovir and steroids) the most generally
      accepted treatment at present is still prednisose at a dose of 1 mg/kg/day.
      CONCLUSIONS: Peripheral facial paralysis is a common condition, usually with no
      apparent cause and an eminently clinical diagnosis. The electrophysiological
      studies determine the prognosis. Currently the standard treatment is still oral
      prednisone.

PMID- 10904953
TI  - [Functional anatomy of the basal ganglia].
AB  - INTRODUCTION: The cerebral cortex of mammals is massively interconnected with the
      basal ganglia. The manner in which the basal ganglia process information has been
      accepted since it was described in the 1980s. It is not a definitive model and
      many aspects of it still need clarification. DEVELOPMENT: The corpus striatum
      (ST) forms the entrance to the basal ganglia circuit (BG) and receives numerous
      afferent fibres from the cerebral cortex. Similarly, the internal segment of the
      globus pallidus (GPi) and the substantia nigra pars reticulata (SNpr) form the
      main nuclei for exit from the circuit and have an inhibitory effect on the pre
      motor neurones of the ventral lamina of the thalamus. Between the entrance
      nucleus and the exit structures are two parallel systems of projection known as
      the direct and indirect pathways. The direct pathway projects monosynaptically
      only on the Gpi/SNpr complex. The indirect pathway projects polysynaptically on
      to the GR/SNpr complex after passing through the external segment of the globus
      pallidus (Gpe) and subthalamic nucleus. Imbalance in the activity of these two
      circuits will lead to alterations in discharge from the Gpi/SNpr complex which
      will cause bradykinesia or hyperkinesia. The bradykinesia or akinesia would be
      caused by increased gabaergic inhibition of the thalamic premotor neurones as a
      result of excessive discharge of the Gpi/SNpr complex. CONCLUSION: Current
      exploration of the electrophysiology of the basal ganglia and careful analysis of
      the clinical findings in lesions circumscribed to certain parts of the thalamus,
      subthalamus and internal globus pallidus in patients with Parkinson's disease,
      have led to the appearance of paradoxical effects, according to the current basal
      ganglia model.

PMID- 10904954
TI  - [Functional surgery of the thalamus in movement disorders].
AB  - INTRODUCTION: Functional thalamic surgery as a treatment for movement disorders
      is half a century old. Although the accumulated experience is wide, their precise
      indications have varied depending on the available alternative therapies.
      DEVELOPMENT: In this article the historical evolution, anatomofunctional basis
      and results of the functional surgery on the motor thalamus are reviewed.
      Considering new advances in this field, the current indications are proposed.
      CONCLUSIONS: Nowadays, thalamic surgery is a valuable therapeutic option for
      patients with different tremor syndromes, when the upper limb tremor is
      disabling, and satisfactory relief with pharmacological treatment cannot be
      achieved. It can also be useful in selected patients with ballism and with
      secondary hemidystonia. When unilateral surgery is considered, both thalamotomy
      and thalamic stimulation can be acceptably safe and effective procedures in
      experienced surgical teams. The main advantage of stimulation is its
      irreversibility, making possible bilateral procedures with a lower morbidity. The
      objective of surgery should be to improve the patients' functional capacities and
      quality of life, therefore, the indication and selection of the procedure should
      be individualized.

PMID- 10904955
TI  - [Surgery of the subthalamic nucleus in Parkinson's disease].
AB  - INTRODUCTION AND DEVELOPMENT: The subthalamic nucleus (STN) plays a crucial part
      in the pathophysiology of Parkinsonism. Its inactivation improves all the main
      signs and symptoms of Parkinson's disease. Surgery of the STN in patients with
      the disease is effective and the benefit/risk relationship very favorable.
      Although the dyskinesias are not a definite limitation, it seems most reasonable
      to use techniques of deep cerebral stimulation until greater experience has been
      obtained with subthalamotomy. The long term efficacy is being studied and
      preliminary data indicate that the clinical benefit obtained is maintained in the
      long term. CONCLUSIONS: More studies are necessary to determine the mechanism of
      action of surgery on the STN. The potential neuroprotector effect of subthalamic
      surgery requires more extensive study.

PMID- 10904956
TI  - [Surgical treatment of dystonia].
AB  - INTRODUCTION AND DEVELOPMENT: Dystonia is a neurological syndrome which is often
      progressive and disabling. The pathophysiological basis is only partly
      understood. Medical treatment often fails. Peripheral surgical techniques can
      alleviate the symptoms of many patients with diverse forms of focal dystonia. In
      patients with generalized dystonia, central surgical techniques are preferable.
      Thalamotomy is the best known technique, although the target is not fully
      defined. Experience with surgery of the pallidum and subthalamus is very limited,
      but results are promising. CONCLUSIONS: More studies are necessary to discover
      the precise potential benefit of these techniques and define the ideal
      candidates. It is important that such studies should be done using rigorous
      methodology and be similar for all groups working on this.

PMID- 10904957
TI  - [Neural transplants en Parkinson disease: clinical results of 10 years of
      experience. Group of Neural Transplants of the CPH].
AB  - INTRODUCTION: At the end of the 1970s people considered the possibility that
      transplants might be useful to replace degenerate specific cell populations, such
      as the mesencephalic dopaminergic neurones in Parkinson's disease (PD). Since
      then this has become an experimental alternative treatment for patients with
      degenerative diseases. The history of transplants of catecholamine producing
      tissues within the brain of patients with PD started in 1985, when Backlund et al
      published the results of the first implants of autologous adrenal medulla in two
      patients with Parkinsonism. Since then, many patients throughout the world have
      benefited from the results obtained using this method. Two main types of tissue
      have been used in this method: autologous adrenal medulla and human foetal
      ventral mesencephalic tissue. DEVELOPMENT: In this paper we first review the
      clinical effects of the diverse types of transplant done to date. Then in the
      second part we give a summary of the clinical results obtained by our group with
      the different types of transplant carried out. We explain their evolution,
      original hypothesis and justify the reasons which led us to use three different
      types of donor material: autologous adrenal medulla, fetal tissue and adrenal
      medulla co-incubated with peripheral nerve. Then, after showing that the clinical
      improvement is different depending on the type of tissue transplanted, we comment
      on the probable reason for the improvement seen in patients with implants.
      CONCLUSION: The transplantation of nervous tissue seems to us to be no longer an
      experimental alternative for the treatment of PD but has become an effective,
      lasting treatment for patients with Parkinson's disease.

PMID- 10904958
TI  - [Protective effect of a mixture of gangliosides in acrylamide neuropathy in
      mice].

PMID- 10904959
TI  - [Neurocysticercosis].

PMID- 10904960
TI  - [Recurrent aseptic meningitis associated with dural vascular malformation].

PMID- 10904961
TI  - [Tarsal tunnel syndrome].

PMID- 10904962
TI  - [Prevalence and incidence of epilepsy in childhood].
AB  - INTRODUCTION: Data coming from the literature regarding the frequency of
      epilepsies in childhood are different, depending on the methodology used, and it
      is noteworthy that there exist very few studies conducted among us. DEVELOPMENT:
      Factors influencing the disparities of the figures found in the literature about
      incidence and prevalence of epilepsies are analyzed; among them, the diversity of
      the diagnostic criteria employed (sometimes not reported, other times imprecise
      or with inclusion of non epileptic episodes), the methodology used in the study
      for data collection (hospitals, surveys, reviews, follow-ups), and the study
      population are prominent. Annual incidence rates that have been published range
      between 11/100,000 and 145/100,000, being the majority between 27/100,000 and
      70/100,000. Estimations about prevalence range between 0.8/1,000 and 49/1,000,
      which in the school population among us means 5.7/1,000.

PMID- 10904963
TI  - [Video-EEG description of epileptic seizures].
AB  - INTRODUCTION: Digital electroencephalography with simultaneous video-EEG
      recording gives invaluable information for the diagnosis of epileptic seizures,
      so that motor episodes which seem to be of cerebral origin may not show
      electrical correlation or on the other hand, electroencephalographic seizures may
      not be accompanied by clinical changes. DEVELOPMENT: The differential diagnosis
      between the different types of epileptic seizures and between these and non
      epileptic motor episodes, have, in this technique, great application as does the
      monitoring of doubtful seizures. We have recorded a large number of epileptic
      seizures with electrical correlation. In some of these cases it may be seen that
      the start of the episode, which clinically appeared to be generalized, showed an
      initial focal discharge although it became secondarily generalized. CONCLUSIONS:
      We believe that this is not an expensive investigation when rationally used for a
      specific purpose, knowing what we are looking for (when this is possible). We
      particularly recommend synchronized recordings in neonatology, where the
      identification of seizures is difficult.

PMID- 10904964
TI  - [A video-EEG description of non-epileptic paroxysmal seizures].
AB  - INTRODUCTION: Paroxystic disorders, especially of motor type, mean that sometimes
      interpretation and classification as epileptic or non-epileptic is difficult. In
      these cases a recording of the episodes synchronized with an EEG may help
      diagnosis. DEVELOPMENT: By means of digital EEG and video we have recorded
      various episodes similar to epileptic seizures, in which lack of correlation
      between the absence of paroxysms on the recording and the clinical anomalies is
      well seen, and therefore this investigation is more than justified. In some cases
      it has allowed medication to be stopped in patients who were being treated as
      though they were epileptics when in fact they were not. In others, such as a case
      of syncope with subsequent convulsions, we showed that on the EEG there was
      slowing followed by reduction in the amplitude representing cortical extinction,
      far from paroxystic hypersynchrony. Hypnagogic nocturnal episodes are
      differentiated from true myoclonic epilepsies. We have shown pseudo-seizures
      which were very similar to the automatisms of epileptic complex partial crises,
      without electrical changes apart from the extracerebral artefacts due to the
      patient's movements. CONCLUSION: In every patient in whom there is reasonable
      doubt as to whether the motor disorders are of cerebral origin or not, a long
      duration synchronized video-EEG is essential, done both whilst awake and asleep.

PMID- 10904965
TI  - [Myoclonic epilepsies in infancy].
AB  - INTRODUCTION: The presence of myoclonus in a patient has different meanings:
      there exist myoclonus without encephalopathy or epilepsy (sleep myoclonus),
      encephalopathies with non-epileptic myoclonus (Kinsbourne's syndrome),
      encephalopathies with epileptic myoclonus (progressive or not), epileptic
      encephalopathies with myoclonic seizures (the classic West and Lennox-Gastaut
      syndromes) and myoclonic epilepsies. DEVELOPMENT: Main types of myoclonic
      epilepsies (benign childhood myoclonic epilepsy, severe-polymorphic-myoclonic
      epilepsy, juvenile myoclonic epilepsy, childhood familial myoclonic epilepsy,
      benign reflex myoclonic epilepsy, as well as progressive myoclonic epilepsies,
      among which progressive myoclonic epilepsy (PME) type 1 (Unverricht-Lundborg's
      disease) and PME2 (Lafora type) are prominent, whereas other entities, such as
      those related to neuronal ceroid lipofuscinosis or mitochondrial cytopathies are
      discussed more briefly) are reviewed, analyzing clinical, EEG and therapeutic
      issues, while the most recent contributions in the field of genetics are
      considered. CONCLUSIONS: Myoclonic epilepsies constitute a very heterogeneous
      type of epilepsy, both in their origin and in their prognosis, with favorable
      forms of course along with other progressive and refractory forms with an ill
      fated prognosis.

PMID- 10904967
TI  - [Clinical aspects of epileptic ion channel disorders].
AB  - OBJECTIVE: One of the recent findings in the investigation of epileptogenesis is
      the localization of new gene situses and mutations of the ion channels. The
      pathology of these ion channel disorders is responsible for a considerable number
      of disorders affecting the central nervous and musculoskeletal systems. Their
      clinical expression is often paroxystic. Mutations cause inactivation of the
      channel, which depending of the degree, conditions the phenotype of the disorder.
      DEVELOPMENT: We studied the main ion channel disorders related to simply
      inherited idiopathic epileptic syndromes in which four genes have been codified
      to date: benign familial neonatal convulsions, generalized epilepsy with febrile
      seizures plus and autosomal dominant nocturnal frontal lobe epilepsy.
      CONCLUSIONS: The ion channels, both voltage dependent and receptor channels, are
      involved in the genesis of idiopathic epileptics syndromes. Their importance is
      due to their contribution to the understanding of epileptogenesis and its
      application to the investigation of drugs which modify the initial cause of the
      seizure. At present, it may be affirmed that the idiopathic epilepsies, or at
      least some of them, seem to form a family of ion channel disorders.

PMID- 10904966
TI  - [Ion channels and epilepsy].
AB  - OBJECTIVE: We review the role of ligand-gated ion channels and voltage-gated ion
      channels as a substrate for the epileptogenesis and as targets in the development
      of new antiepileptic drugs. DEVELOPMENT: Voltage-gated calcium channels are
      involved in the release of neurotransmitters, in the sustained depolarization
      phase of paroxysmal depolarisation shifts (PDS), and in the generation of
      absences; they are also the genetic substrate of generalized tonic-clonic
      convulsions and absence-like pattern seen in some mice. The voltage-gated
      potassium channel has been implicated in the hyperpolarization-phase of PDS, it
      is the genetic substrate of the long QT syndrome, benign neonatal epilepsy, and
      episodic ataxia/myokymia syndrome, and it is the target of some antiepileptic
      drugs which activate this channel. The voltage-gated sodium channel is the target
      of most of the classical and newer antiepileptic drugs; it is also the substrate
      for generalized epilepsy with febrile seizures plus. The sodium channel of the
      nicotinic acetylcholine receptor is the substrate for nocturnal frontal lobe
      epilepsy. The sodium channels of the AMPA and KA glutamate receptors have been
      proposed as substrate for juvenile absence epilepsy and are a target for new
      antiepileptic drugs which inhibit it. The calcium channel of the NMDA glutamate
      receptor has been implicated in the sustained depolarization-phase of PDS and in
      epileptogenesis after kindling and is a main target for new antiglutamate drugs.
      The chloride channel of the GABAA receptor is responsible for the rapid
      hyperpolarization of PDS, it has been involved in epileptogenesis after kindling,
      it may be the substrate of the Angelman syndrome, and it is activated by many
      classical and new antiepileptic drugs. CONCLUSION: The knowledge of the role of
      the ion channels in the epilepsies is allowing the design of new and more
      specific therapeutic strategies.

PMID- 10904969
TI  - [Epileptic syndromes in the first year of life and congenital errors of
      metabolism].
AB  - INTRODUCTION: Early infantile epileptic encephalopathy includes two epileptic
      syndromes of the neonatal period: the Ohtahara syndrome and early myoclonic
      epilepsy of Aicardi. Both conditions are severe forms of neonatal epilepsy with
      bad prognosis (both neurological and vital). Some cases are due to metabolic
      defects or cortical dysplasia-type cerebral malformations. DEVELOPMENT: We
      propose to establish two major syndrome groups according to aetiology:
      cryptogenic and secondary (as determined in West's syndrome). West's syndrome has
      many aetiologies, including congenital errors of metabolism. The incidence of
      cases due to phenylketonuria or hypoglycemia is falling. However, new metabolic
      diseases, such as the syndromes of glycoproteins deficient in carbohydrates,
      biotinidase deficit or glucose protein transporter, appear to be responsible for
      clinical pictures of West's syndrome. In all these cases, and especially the
      idiopathic ones, it is useful to do extensive metabolic investigations since
      sometimes metabolic diseases give rise to these syndromes, so the prognosis,
      treatment and genetic counselling may be modified. CONCLUSION: In the text we
      review the congenital errors of metabolism involved in the aetiology of the
      epileptic syndromes seen in the first year of life.

PMID- 10904968
TI  - [Recent aspects of the genetics of epilepsy].
AB  - INTRODUCTION: In recent years major advances have been made in localizing the
      genes responsible for different types of epilepsy. This progress has been
      determined, amongst other things, by the discovery of diverse genotypes which do
      not always correspond to the same phenotype, a fact which has opened interesting
      fields of investigation. However, all these advances make it necessary to
      restructure the current classification of the epilepsies and epileptic syndromes
      of the International League Against Epilepsy (ILAE), in which the new syndromes
      which have now been identified were not contemplated, in spite of having clearly
      defined characteristics. DEVELOPMENT: The new approach to the genetics of
      epilepsy and the progress which, no doubt, will be made in the future will lead
      to a new attitude not only regarding diagnostic protocols, in which it will be
      necessary to know all the possible variations of the phenotypes of the different
      syndromes identified, but also the relevant considerations regarding genetic
      counselling, programmes of treatment and preventive measures which will have to
      be undertaken. We discuss the genetic aspects of different epileptic disorders,
      including those classically considered to be of idiopathic origin, to those of
      symptomatic origin whether due to structural changes in the nervous system or
      metabolic diseases with epileptic features at some stage of the condition. Five
      categories are established following these different criteria: 1. Idiopathic
      generalized epilepsies, 2. Partial epilepsies, 3. Progressive myoclonic
      epilepsies, 4. Dysgenetic syndromes and chromosome anomalies and 5. Metabolic
      diseases.

PMID- 10904970
TI  - [Inter-relationships of the epileptic encephalopathies of infancy].
AB  - INTRODUCTION: The epilepsies of childhood are much more variable in expression
      and outcome than those of adults: the clinical and EEG features of epilepsy can
      change considerably with age. DEVELOPMENT: The neonatal epileptic encephalopathy,
      West and Lennox syndromes are present at different age, and each one shows a
      stereotyped association of seizures and EEG findings that are essentially
      pathognomonic for each syndrome. It is possible that these syndromes represent
      successive stages in maturation of an epileptic process, although there are
      differences between the disorders that may not be explained by the concept of age
      dependent encephalopathy. Clinically it is very important to differentiate signs,
      symptoms and EEG findings in the West syndrome from the Lennox syndrome
      transition. CONCLUSION: The study of the age-dependent epileptic encephalopathies
      will contribute to the understanding of the pathophysiology of epilepsy.

PMID- 10904971
TI  - [Photogenic epilepsy].
AB  - INTRODUCTION: The commonest reflex seizures are those induced by visual stimuli,
      and amongst these, those provoked by intermittent luminous stimulus. DEVELOPMENT:
      A directed anamnesis and suitable intermittent light stimulation are important
      during electroencephalographic studies for the confirmation of the diagnosis of
      photosensitive epilepsy. The photogenic epilepsies, that is those in which all
      the epileptic seizures are provoked by visual stimuli, form a small group of
      epilepsies within the idiopathic generalized epilepsies with their onset during
      adolescence. These seizures have had great social impact, since media diffusion
      of the possibility of their appearance whilst watching television or playing
      video games. CONCLUSION: The correct diagnosis and preventive measures, together
      with the correct anti-epileptic treatment are in favour of a good prognosis in
      the great majority of patients.

PMID- 10904972
TI  - [Reflex epilepsies].
AB  - INTRODUCTION: Reflex seizures are provoked by a specific sensory stimulus.
      Approximately 6% of all epileptic patients have reflex seizures. For
      identification of these seizures it is necessary to take a directed history and
      make an EEG study whilst the patient is being exposed to the stimulus, which will
      confirm the diagnosis. DEVELOPMENT: Many stimuli are effective in provoking
      reflex seizures, the commonest are visual. Amongst the various epileptic
      syndromes there are different types of epilepsies with reflex seizures which
      generally correspond to idiopathic generalized epilepsies. The physiopathogenic
      mechanisms are usually complex. The cerebral cortex corresponding to the function
      which induces the epileptic crisis is hyperexcitable, and is the cause of an
      identifiable lesion or dysfunction without an underlying lesion. CONCLUSION: The
      diagnostic importance of reflex seizures is that when some formerly drug
      resistant patients can control the mechanism which triggers off their seizures
      they attain good control of them.

PMID- 10904973
TI  - [Epilepsies and language disorders].
AB  - OBJECTIVE: To study the effects of the epilepsies, the seizures and
      electroencephalographic discharges on the cognitive function of the child,
      specifically his language. We consider the relationship between developmental
      dysphasia and epilepsy, bearing in mind that this association may occur
      fortuitously, as a consequence of the same cause or taking the epilepsy to be
      responsible for the language disorder, as seizures or continuously (epileptic
      aphasia). DEVELOPMENT: We assess the relation between developmental aphasia and
      seizure aphasia in the epilepsies, especially the syndrome of acquired epileptic
      aphasia of Laundau-Kleffner (LKS). Based on the findings in the literature and a
      personal series of nine cases, we studied their general characteristics, clinical
      heterogeneity, associated clinical signs and EEG changes (present in all
      patients); coexistence of convulsive seizures (67-90%); aetiopathogenic findings
      invoked but not currently conclusive; negative neuroimaging findings apart from
      some SPECT and PET data; differential diagnosis; clinical course and prognosis
      difficult to predict. The pharmacological and/or surgical treatment, complemented
      by logopedics and psychopedagogics (good results in < or = 50% of the cases), the
      unpredictable course of LKS has to be assessed cautiously. CONCLUSIONS: No direct
      relation can be confirmed between epilepsy and language disorders, although a
      relationship may be found in some cases. The hypothesis that LKS, continuous
      spike-and-wave during slow sleep and partial benign atypical epilepsy are the
      severe, moderate and mild forms of the same epileptic syndrome is generally
      accepted. This appears during a phase of maturation in which the brain is
      particularly vulnerable, and is characterized by continuous spike-and-wave
      complexes during slow sleep, which lead to cognitive and behaviour disorders.

PMID- 10904974
TI  - [Antiepileptic drugs and the liver].
AB  - OBJECTIVES: We review the metabolism of antiepileptic drugs with particular
      emphasis on the formation of active metabolites and toxic intermediate
      metabolites, together with the factors altering this and the possibility of
      interactions between the antiepileptic drugs themselves and with other drugs.
      DEVELOPMENT: Most antiepileptic drugs undergo complex metabolic processes in the
      liver which determine the time course of their concentration in the organism and
      therefore their therapeutic and toxic effects. Also, the processes by which drugs
      are metabolised may be influenced by many physiological and pathological factors,
      as well as the presence of other drugs which cause clinically relevant
      interactions. We analyze the function of the liver in the metabolism of these
      drugs with special reference to the microsome oxidation mediated by cytochrome P
      450 and the glucuronidation catalysed by glucuronosyltransferase and the
      processes of enzyme induction and inhibition. Subsequently, we describe the
      metabolism of the antiepileptic drugs, their main routes of elimination, factors
      affecting this, role of the active and intermediate metabolites and the
      involvement of the enzyme induction and inhibition underlying the interactions of
      these drugs. Finally, we describe the metabolism of the most important classical
      and new antiepileptic drugs, the isoforms of cytochrome P-450 involved, the
      factors altering this and the most relevant interactions with other antiepileptic
      and non-antiepileptic drugs. CONCLUSION: Knowledge of the paths by which the
      antiepileptic drugs are metabolised, particularly the isoforms of cytochrome P
      450 involved facilitates understanding of the influence of various factors on the
      metabolism of drugs, and also of their complex interactions.

PMID- 10904975
TI  - [Antiepileptic drugs and carnitine].
AB  - INTRODUCTION: Carnitine is an nonproteic nitrogenated compound acid present in
      all mammalian tissue and its principal activity is the long-chain fatty acid
      transport across the mitochondrial membrane for beta-oxidation. DEVELOPMENT:
      Carnitine levels are maintained by absorption from dietary, endogenous synthesis
      in the liver and renal reabsorption. An alteration in concentration could be due
      to an abnormality in some of mentioned mechanism or to inherited errors in
      metabolism. A reduction in serum carnitine levels have been reported in patients
      with antiepileptic drugs (AED) use. While valproic acid as monotheraphy or in
      combination with other AED have been associated principally, some contradictory
      studies demonstrated that other AED specifically carbamazepine, phenytoin and
      phenobarbital, also cause carnitine deficiency in about 21% of the patients whom
      they are administered. CONCLUSION: This study was designed to investigated the
      relationship between the carnitine levels and the presence of symptoms in
      patients with seizures whom are treated with a AED alone or in combination.

PMID- 10904976
TI  - [Mortality in epilepsies].
AB  - INTRODUCTION: The overall mortality associated with epilepsy has been estimated
      to be two or three times that of the general population. Data from contemporary
      studies show excess mortality in the first decade of life and the first few years
      after diagnosis. DEVELOPMENT: The underlying disease of which epilepsy is a
      symptom is the main cause of death in new cases, while the epilepsy itself is a
      major cause in chronic epilepsy. Sudden unexpected death in epilepsy is probably
      the most common category of epilepsy-related deaths and is likely to be seizure
      related in the great majority of cases. The mechanisms involved in sudden
      unexpected death in epileptics may include autonomically mediated cardiac
      arrhythmia and neurogenic pulmonary edema. Other causes of death are status
      epilepticus, trauma, burns or drowning secondary to a seizure, severe aspiration,
      food bolus, and the presence of significant cardiorespiratory disease.

PMID- 10904977
TI  - [Current data on vigabatrin].
AB  - OBJECTIVE: We analyze the most usual pharmacokinetic and pharmacodynamic
      characteristics of vigabatrin, considering the current therapeutic indications
      which define its greatest usefulness in seizures and partial epileptic syndromes.
      DEVELOPMENT: At the same time, we assess the adverse effects described with
      special reference to peripheral changes in the visual field, although their mode
      of production is still unknown; similarly we describe the relevant hypotheses. We
      emphasize the usefulness of this drug in some seizures and epileptic syndromes,
      such as the infantile spasms of West's syndrome. Finally, we emphasize the need
      to establish an equilibrium between risks and benefits, so that this therapeutic
      option may still be used in spite of the risks, particularly when other options
      are not free of serious side-effects, as occurs with the corticosteroids or
      valproic acid at high doses.

PMID- 10904978
TI  - [Current data on lamotrigine].
AB  - OBJECTIVE: We analyze the most usual characteristics of lamotrigine and review
      the current antiepileptic indications. Similarly, we consider current hypotheses
      as to the mode of action during seizures which initially were not considered to
      be the main indication for use of the drug, as occurs with absence seizures.
      DEVELOPMENT: We review the adverse effects and emphasize the need to attain the
      desired dose after a slow, progressive increase in dosage, particularly when it
      is associated with valproic acid, since this therapeutic combination is very
      effective in refractory epilepsies. We also mention the favourable effect on the
      quality of life of the patients treated with this drug and in those in whom an
      obvious euthymic effect is seen, as well as the benefit observed in patients with
      mental retardation.

PMID- 10904979
TI  - [Current data on gabapentin].
AB  - OBJECTIVE: To review the current data on gabapentin (GBP) with regard to its
      mechanism of action, pharmacokinetic characteristics, clinical efficacy,
      tolerance and mode of administration. DEVELOPMENT: GBP has a multiple mechanism
      of action which justifies its use in many clinical conditions besides epilepsy.
      These include neuropathic pain, psychiatric disorders, disorders of movement, and
      migraine. Its pharmacokinetic characteristics are nearly those of an ideal drug,
      with no interactions. Regarding clinical efficacy, there is much evidence of this
      in polytherapy and in monotherapy in adults and children with partial crises,
      with rare adverse effects and the exceptional possibility to establish the total
      dose of GBP in only a few days. CONCLUSIONS: GBP is an effective drug in patients
      of all ages with partial crises. Because of its excellent tolerance and
      decreasing dose-dependent kinetics, conditioned by less absorption of the drug,
      we recommend the administration of GBP at doses higher than those normally used.
      Thus we suggest a dose of 900 to 2,400 mg/day in patients with a new diagnosis,
      of 1,800 to 3,600 mg/day as a second therapeutic alternative and even 2,400 to
      4,800 mg/day when other antiepileptic drugs have failed to be of use.

PMID- 10904980
TI  - [Current data on topiramate].
AB  - OBJECTIVES: To review current knowledge regarding the mechanisms of action,
      pharmacokinetics, clinical efficacy and the tolerance of topirimate (TPM) and
      describe the Spanish experience of the use of this drug in 224 patients of all
      ages. DEVELOPMENT: TPM is a new drug which affects practically all the mechanisms
      involved in the production of epileptic seizures, which means that it is a broad
      spectrum antiepileptic drug. After reviewing the mechanisms of action and
      pharmacokinetic characteristics of TPM, we consider the efficacy of the drug in
      224 patients of all ages with all types of epileptic seizures. CONCLUSIONS: In
      patients of all ages with uncontrolled epileptic seizures treated with TPM, the
      frequency of their seizures was reduced by over 50% in 78% of the patients and
      the seizures were abolished in 25% of the total cases. The drug was generally
      well tolerated. Side-effects leading to suspension of the drug occurred in only
      5% of the cases. TPM is an effective drug which is well tolerated in patients of
      all ages and with all kinds of epilepsy.

PMID- 10904981
TI  - [Current data on tiagabine].
AB  - OBJECTIVE: To review current data regarding the mode of action, pharmacokinetics,
      clinical efficacy and tolerance of tiagabine (TGB). DEVELOPMENT: TGB is a drug
      which boosts gabergic inhibition by blocking the re-uptake of synaptic GABA by
      the glia and neurones. This specific mode of action leads to an antiepileptic
      effect in patients of all ages with partial seizures. The efficacy of TGB is
      complemented by good tolerance, especially when it is introduced slowly, over a
      period of eight weeks. This form of administration is also used with other new
      antiepileptic drugs, such as lamotrigine and topiramate. We consider the data
      regarding efficacy and tolerance found in the clinical trials and studies
      reported in the literature. CONCLUSIONS: TGB is an effective, well-tolerated drug
      when used in patients with difficult-to-control partial crises. However, it
      should also be used in patients with less difficult-to-control seizures and in
      previously untreated patients so as to properly define its efficacy and
      tolerance.

PMID- 10904982
TI  - [Surgical treatment of epilepsies: criteria for the selection of patients and
      results].
AB  - INTRODUCTION: Approximately 20% of all epileptic patients are not satisfactorily
      controlled by the available antiepileptic drugs. Some of these patients have
      epileptic syndromes which could potentially be treated by surgery. DEVELOPMENT:
      The technological advances applied to diagnostic and therapeutic methods have
      improved the identification of epileptic patients who may benefit from surgery.
      Up to 80% of the patients with focal epilepsies symptomatic of well defined
      lesions may become free of seizures after excision of the lesion or epileptogenic
      focus. Other forms of epilepsy, such as the so-called catastrophic infantile
      forms, may improve temporarily when techniques such as hemispherectomy or
      callosotomy are used. The morbidity and mortality of these surgical procedures
      are minimal. The results depend on correct selection of the patients. A strict
      protocol for rigorous evaluation of the patients should be used, with the
      collaboration of neurologists, epileptologist neuropaediatricians,
      neuropsychologists, neurophysiologists, neuroimaging specialists, psychiatrists
      and neurosurgeons. There should first be clear answers to three key questions: 1.
      Who is a good candidate? 2. How should the selection be made? and 3. When is the
      best time for evaluation? CONCLUSIONS: At present it seems clear that the surgery
      of epilepsy is used less than it could be. It is therefore necessary to encourage
      the development of specialist units to select patients and treat them, and to
      develop the means whereby patients can obtain this highly specialized attention.

PMID- 10904983
TI  - [Economic aspects of epilepsy].
AB  - INTRODUCTION: The economic magnitude of epilepsy is determined by its effect on
      the employment status of the patients, the cost of drug treatment for them and
      the healthcare system and the repercussion worldwide. DEVELOPMENT: Studies of the
      cost of the disease show that it has economic importance due to the sum of the
      direct and indirect costs caused by it. In the case of epilepsy, the results of
      studies in various countries led to the creation of a Commission on Economic
      Aspects of Epilepsy. The lack of epidemiological studies regarding epilepsy in
      Spain may explain the lack of publications on this subject in our country. The
      percentage of the total cost due to antiepileptic drugs is considerable and will
      probably increase in the future. The pharmaco-economic evaluation made by cost
      benefit, cost-effectiveness, cost-usefulness analysis and studies to minimize
      costs should serve to use healthcare resources in the most effective manner and
      justify the rational use of the new antiepileptic drugs. CONCLUSIONS: The
      economic impact of epilepsy is added to the repercussion of the disease itself on
      the patient and his family. The different distribution of costs in children and
      adults with epilepsy suggest the need for intervention at an early age to try to
      reduce the long term economic and personal repercussions. The pharmaco-economic
      evaluation of the new antiepileptic drugs will make it clear whether their
      considerable cost is worth paying for their greater effectivity.

PMID- 10904984
TI  - [Fabry disease: clinical aspects and therapeutic perspectives].
AB  - Fabry's disease is one of the lysosomal disorders. It is due to a hereditary
      alpha-galactosidase A defect with X-linked recessive transmission. A majority of
      hemizygotes develop severe multisystemic involvement (classic form), dominated by
      relentless renal failure and progressive neurological and cardiac lesions.
      Nevertheless, some affected individuals retain sufficient enzyme activity and
      long remain asymptomatic (atypical form); their main manifestation is
      hypertrophic cardiomyopathy. Female carriers are usually asymptomatic; 15%,
      however, have severe involvement of one or more organs. Laboratory, histological
      and molecular diagnosis identifies 100% of hemizygotes and over 80% of
      heterozygotes. With recent developments in molecular genetics it is possible to
      produce the human recombinant enzyme alpha-GALA. Its effects in hemizygous
      patients remain to be evaluated. In addition, the results of a trial of gene
      therapy in a Fabry's disease gene knocked-out mouse appear promising. These new
      therapeutic approaches will probably soon provide substitutive treatment for
      Fabry's disease as well as for so-called "orphan" diseases.

PMID- 10904985
TI  - [Prevalence of sleep disorders in an employed Swiss population: results of a
      questionnaire survey].
AB  - BACKGROUND: The aim of the study was to demonstrate the variety of sleep
      disorders occurring in a working population in Switzerland and to estimate the
      prevalence of the main sleep disorders in this Swiss cohort. We also intended to
      demonstrate that with just a few systematic questions a straightforward
      diagnostic workup is possible in general practice. METHODS: A questionnaire was
      sent to all 1473 clerks of the Berne main post office. The questions allowed a
      choice between "yes" or "no", or often (= +3), occasionally (= +2), rarely (= +)
      and never (= 0). Daytime sleepiness was assessed by the Epworth Sleepiness Scale.
      RESULTS: 668 questionnaires (45%) were available for analysis. Daytime
      sleepiness, assessed by an Epworth score > or = 10, was found in 13% of the
      respondents. Short sleep (< 7 h sleep) was reported in 47%, and long sleep (> 9 h
      sleep) in 5% of this population. Specific questions clearly suggested obstructive
      sleep apnoea in 6%, restless-legs syndrome in 4%, disorders of initiating and
      maintaining sleep in 19% and narcolepsy in 0.5% of respondents. CONCLUSION:
      Chronic sleep insufficiency and sleep complaints appear to be frequent in this
      relatively young Swiss working population. The questionnaire-based estimated
      prevalence of the main sleep disorders is comparable to previously published
      international data.

PMID- 10904986
TI  - [Had luck? Lucky charms in the first medical propaedeutics].
AB  - The relevance of using lucky charms in the examination room has not been well
      studied. In this analysis the frequency and results of using lucky charms have
      been determined in a group of medical students (n = 676) sitting the first
      examination in the medical curriculum (first propaedeutics). Approximately 10% of
      all candidates took lucky charms with them into the examination room. Lucky
      charms were worn significantly more often by female examinees than by males.
      However, examination results were not significantly better among charm wearers
      than those without. The commonest charms were in the form of ladybirds or pigs,
      most of the other 27 also being animal representations.

PMID- 10904987
TI  - New strategy to treat glomerular inflammation by inhibition of mesangial cell
      matrix metalloproteinases.
AB  - Therapy of inflammation often requires the attenuation of excess cell
      proliferation and of extracellular matrix (ECM) accumulation. It is increasingly
      recognised that matrix metalloproteinases (MMP) play an important role in the
      regulation of these two features. For our studies, experimental mesangial
      proliferative glomerulonephritis and cultured mesangial cells provided the
      inflammation model and the opportunity to evaluate a new therapeutic strategy
      based on MMP inhibition. In vitro inhibition of MMP activity and synthesis
      successfully returned the inflammatory mesangial cell phenotype to the normally
      occurring resting state. In vivo, excess mesangial cell proliferation and ECM
      accumulation in experimental mesangial proliferative glomerulonephritis were
      significantly ameliorated by the use of a synthetic MMP inhibitor. Interestingly,
      these inhibitors lead to increased mesangial cell apoptosis. In conclusion, the
      antiproliferative effect of MMP inhibitors opens new perspectives in the therapy
      of inflammation, probably even beyond the scope of kidney diseases.

PMID- 10904988
TI  - [Splenic infarct as the etiology of acute abdomen].

PMID- 10904989
TI  - Developmental antecedents of sexual coercion in juvenile sexual offenders.
AB  - Previous research has linked adult sex offending behavior to a multiplicity of
      variables, including juvenile delinquency and the experience of childhood abuse.
      The purpose of this study was to explore developmental pathways among childhood
      abuse, juvenile delinquency, and personality dimensions possibly conducive to
      adolescent sexual coercion. Using a retrospective self-report inventory, we
      measured the extent to which juvenile sexual offenders experienced childhood
      trauma, engaged in adolescent delinquency, and exhibited particular dispositions
      and cognitive biases. The effects of childhood and adolescent antecedents on
      sexual coerciveness were then analyzed through simultaneous multiple regression
      path analyses. Results suggest that sexual compulsivity and hypermasculinity,
      through misogynistic fantasy behavior, significantly discriminate verbally and
      physically coercive juvenile offenders from those offenders who do not report
      using force in their offenses. Results also suggest that alcohol abuse may play a
      more salient role in the expression of coercive juvenile sexual coercion than
      previously hypothesized.

PMID- 10904990
TI  - Comparison of perpetration characteristics between male juvenile and adult sexual
      offenders: preliminary results.
AB  - This study investigated the characteristics of the sexual abuse perpetrated by 16
      juvenile (JSO) and 19 adult sexual offenders (ASO). Data were collected from a
      randomly selected group of males who received psychotherapy services at a
      community agency. The results revealed significant differences between the JSOs
      and the ASOs on the number of committed offenses, length of sexual relationships
      maintained with victims, quality of these relationships, nature of the sexual
      acts committed, and presence of force during abuse incidents. The results show
      similarities and differences in the sexual abuse characteristics perpetrated by
      juveniles and adults.

PMID- 10904991
TI  - Sexual offenders' implicit planning: a conceptual model.
AB  - In recent years empirical research, clinical observation, and theoretical models
      about sexual offending have emphasized the importance of problem solving and
      decision making throughout different phases in the offense chain. This work
      suggests that sometimes offense planning is explicit, systematic, and analytical,
      while at other times it appears to be implicit and intuitive. The latter style of
      decision making has been called seemingly unimportant decisions. We attempt to
      provide an explanation of offenders' implicit decision making and suggest two
      social cognitive mechanisms capable of generating these types of decisions. We
      believe that implicit decision making in offenders has the appearance of
      automaticity, that is, decision making that is implicit, fast, relatively
      autonomous, frequently associated with a lack of control, effortless, and
      occurring without conscious awareness. Drawing from diverse theoretical sources,
      we hypothesize that these types of decisions are generated by underlying
      automatic goal dependent action plans. More specifically, we suggest that there
      are at least two types of automatic goal dependent plans evident in offenders'
      decision making: offense scripts and mental simulations. We draw implications for
      generating future hypotheses and provide suggestions for future research.

PMID- 10904992
TI  - Prediction of recidivism in extrafamilial child molesters based on court-related
      assessments.
AB  - One hundred ninety-two convicted extrafamilial child molesters were followed for
      an average of 7.8 years after their conviction. The percentage of men who had
      committed a sexual, a violent, or any criminal offense by the 12th year was 15.1,
      20.3, and 41.6, respectively. The sexual recidivists, compared with the
      nonrecidivists; demonstrated more problems with alcohol and showed greater sexual
      arousal to assaultive stimuli involving children than to mutually consenting
      stimuli with children. The violent recidivists, compared with the nonrecidivists,
      were more likely to have a history of violence in the families in which they were
      raised and were rated significantly more psychopathic on the Psychopathy
      Checklist--Revised (PCL-R). They also showed more sexual arousal to stimuli
      depicting mutually consenting sexual interactions with children than to adult
      stimuli. In terms of any criminal recidivism, recidivists were younger, had
      completed fewer years of school, and were raised in psychologically more harmful
      family environments compared with nonrecidivists. They also reported that, before
      16 years of age, they were more likely to have been physically abused and were
      more likely to have been removed from their homes compared to those that did not
      recidivate. In addition, recidivists demonstrated more general hostility on the
      Buss-Durkee Hostility Inventory and were rated significantly more psychopathic on
      the PCL-R. The phallometric assessments revealed, that the criminal recidivists,
      compared to the nonrecidivists, showed more sexual arousal to stimuli depicting
      coercive sexual activity with children than consenting sexual activities with
      children. In addition, they showed more sexual arousal to scenes depicting adult
      rape then adult mutually consenting sex. Finally, the recidivists also had more
      charges or convictions for violence and any criminal acts. The small number of
      significant differences between recidivists and nonrecidivists in the sexual and
      violent categories precluded an attempt to determine which combination of factors
      meaningfully predicted reoffending. However, for criminal recidivism, a stepwise
      discriminant function analysis to assess the combination of factors that most
      successfully distinguished between groups in terms of criminal recidivism was
      significant, with subjects' age, total number of criminal convictions, and
      pedophile assault index being retained for optimal prediction. The procedure
      correctly classified 70.6% of the original group, 82.8% of the nonrecidivists,
      and 52.6% of the recidivists. PCL-R Total Score alone was equally successful in a
      similar discriminant function.

PMID- 10904993
TI  - Attitudinal effects of degrading themes and sexual explicitness in video
      materials.
AB  - This study examined the independent and interactive effects of sexual
      explicitness and degrading themes toward women on mens' attitudes following
      exposure to video presentations of male-female interactions. Subjects were 83
      male college students who viewed video vignettes under one of four stimulus
      conditions: (a) sexually explicit/degrading, (b) sexually explicit/nondegrading,
      (c) nonexplicit/degrading, and (d) nonexplicit/nondegrading. Results revealed
      that men exposed to degrading material, regardless of explicitness, were
      significantly more likely to express attitudes supportive of rape, while
      explicitness had no significant main or interactive effect on these attitudes.
      Further, the interaction of explicitness with degradation was found to impact
      scores on a measure of sexual callousness. Theoretical and clinical implications
      of these findings are discussed.

PMID- 10904994
TI  - Conservative treatment vs. mastectomy without radiotherapy in aged women with
      breast cancer--a prospective and randomized trial.
AB  - OBJECTIVE: To determine whether tumorectomy with tamoxifen in women over 70 years
      achieves the same treatment results as mastectomy plus tamoxifen. MATERIAL AND
      METHODS: Prospective randomized analysis of 121 patients over 70 with breast
      cancer clinically negative axilla and tumor up to 4 cm diameter. Randomization
      was according to even or odd birth month. Branch A: Madden operation + tamoxifen
      20 mg OD (once/day). Branch B: Tumorectomy to disease free margins + tamoxifen 20
      mg OD. RESULTS: Survival rate of five years for the Madden operation was 69% and
      for tumorectomy 71.4% with a mortality from other causes of 23.1%. Survival
      probability (specific death) at 5 years was of 93.4% for the Madden group and
      95.2% for tumorectomy. A significant increase of the mortality was observed in
      those patients that had recurrences, no matter of treatment given. Specific death
      cause did not vary with age, but did for other causes, this being significant.
      CONCLUSIONS: Tumorectomy plus tamoxifen demonstrated to be as effective as Madden
      Op. plus tamoxifen in women over 70 years with T1-T2-N0 disease.

PMID- 10904995
TI  - Long-term follow-up results of irradiation alone or combined with surgery in
      stage I-IV carcinoma of the uterine cervix.
AB  - OBJECTIVE: Evaluation of side effects and prognostic factors for survival in
      cervical carcinoma treated with radiation therapy +/- surgery. MATERIAL AND
      METHODS: From January 1986 to June 1995 277 female patients with cervical
      carcinoma were treated by irradiation in the Department of Radiation Oncology of
      the University of Munster. Out of them 224 patients were evaluable for clinical
      features. 20 of them did not undergo complete radiation series and 14 patients
      received irradiation for recurrent disease, therefore 190 patients (n = 103 pts.
      with primary irradiation, n = 87 pts. with postoperative irradiation) were
      analyzed for survival/therapeutic features. RESULTS: 5-year-disease-free survival
      rates after primary irradiation: (FIGO I number of patients too small); FIGO II
      (n = 33 pts.) 52%; FIGO III (n = 44 pts.) 39.5%; FIGO IV (n = 18 pts.) 26%. 5
      year-survival rates after postoperative irradiation: pT1 (n = 43 pts.) 87.4%; pT2
      (n = 37 pts.) 47%. As significant prognostic factors for disease specific
      survival after irradiation alone the hemoglobin bloodlevel at the beginning of
      radiation therapy, tumor stage according to FIGO, tumor size and irradiation of
      the paraaortic region were revealed. As significant prognostic factors for
      disease free survival after postoperative irradiation were seen: interval between
      surgery and the beginning of radiation therapy, tumor invasion of parametria,
      postoperative stage, involvement of lymph nodes and lymph-/hemangiosis. The
      documented side effects among all patients corresponded to data found in
      literature. CONCLUSIONS: Prognostic factors for disease free survival in our
      patients corresponded to the results of other studies. Acute and chronic side
      effects after irradiation were within the usual range. Especially in case of
      additional irradiation of the paraaortic region we could not find an accumulation
      of side effects. An elevation of disease free survival rates in patients with
      cervical carcinoma probably could be obtained by improving positional techniques
      for irradiation or changing fractionation schedules.

PMID- 10904996
TI  - [Severe cardiovascular complications relating to Gemeprost therapy].
AB  - The use of gemeprost vaginal pessaries is generally thought to be a method with
      little complications used for cervical softening within the first two trimesters
      of pregnancy. Though in our hospital two cases presented with severe
      cardiovascular reactions, to be attributed to the effect of prostaglandins. The
      first patient experienced a severe cardiogenic shock due to vasospasm several
      hours after primary administration of gemeprost vaginal pessaries and a cerebral
      stroke some hours later. The second patient suffered of a myocardial infarction
      ensuing from coronary spasm.

PMID- 10904998
TI  - Globalization and the German model of capitalism--erosion or survival?
AB  - The German business system has been regarded as a particularly tightly coupled
      system, with embeddedness of even multinational companies (MNCs) in their home
      base as particularly deep. A study of the impact of companies' changing
      internationalization, if not globalization, strategies is therefore especially
      suited to test competing claims about their effects on the German business
      system. Are we experiencing an erosion of this system, an adaptation in a largely
      path-dependent way, or even a greater specialization and stronger crystallization
      of the German business system? To investigate these questions, the paper examines
      a small number of German MNCs in their domestic and international context. More
      particularly, the work focuses on whether and how their emergent globalization
      activities affect the reproduction or erosion of the three institutional
      complexes which shape the factors of production: the financial system; the
      innovation system; and the industrial relations system. The paper concludes that
      a new type of transformation--hybridization--is emerging. It is regarded as a
      consequence of German companies' growing integration into a global economic
      system.

PMID- 10904997
TI  - [Computer-assisted cardiotocogram analysis--from descriptive to perinatal expert
      system].
AB  - The interpretation of cardiotocograms is essentially for perinatal management, it
      remains labour intensive and depends on training and experience. With the
      development of modern analysing systems with conventional classification
      techniques, it seems possible to introduce expert systems and neuronal networks
      for a better interpretation and classification of cardiotocograms. Techniques of
      artificial intelligence are powerful tools and should be integrated in future
      systems. Because CTG-analysis--as a single procedure--is only of limited value
      for sufficient fetal prognosis, we conclude that computer aided CTG-analysis in
      combination with additional fetal parameters, for example partial oxygen
      pressure, will allow the development of future sufficient perinatal expert
      systems. Nothing should hinder future integration of computerized cardiotocogram
      analysing systems into everyday clinical routine and to connect it to obstetrical
      databases.

PMID- 10904999
TI  - Compromising positions: emergent neo-Fordisms and embedded gender contracts.
AB  - This paper adopts a regulation framework to chart the emergence of neo-Fordism as
      a flexible accumulation regime and mode of social regulation. Neo-Fordism relies
      on old Fordist principles as well as incorporating new models of emergent post
      Fordisms; old and new social relationships, in their particular combination,
      specify the trajectory of national variants. I argue that Fordist bargains
      institutionalized the terms of a compromise between labour, capital and the
      state. These bargains embedded a male-breadwinner gender contract compromising
      women's positions and standardizing employment contracts around the needs,
      interests and authority of men. A focus on compromises and contracts makes
      visible the differentiated gender effects of work transformation in each country.

PMID- 10905000
TI  - Market returns? Gender and theories of change in employment relations.
AB  - This paper explores recent arguments about the marketization of female labour, in
      the context of a wider analysis of the role of concepts like 'the market' and
      'individualization' in sociological accounts of change in employment relations.
      It will be argued that within sociology there has been a tendency for rapid,
      large-scale changes in employment relations to be characterized as the breakdown
      of social influences or structures and as the emergence of atomized, individuated
      market forces. In the most recent models, change in the nature of gendered
      positions within employment are presented in terms of a decline of social
      structuring and social constraint. These emergent accounts hold similarities to
      classical economics, and to Marx's and Weber's accounts of employment, which also
      characterized new forms of employment relations in terms of the emptying of their
      social content and their replacement by market forms. We offer an alternative,
      moral economy, perspective which foregrounds the continued significance of social
      relations in the structuring of employment and employment change. We develop the
      argument through an analysis of gendered patterns of employment and change in
      family form.

PMID- 10905001
TI  - The concept of social care and the analysis of contemporary welfare states.
AB  - Care is now a widely-used concept in welfare state research, firmly established
      in the literature by feminist analysis. We believe that the concept as it has
      been used and developed to date has limitations that have hampered its
      development as a general category of welfare state analysis. In essence we argue
      that the political economy aspects of the concept have remained underdeveloped.
      The main purpose of this article is to elaborate a care-centered concept--which
      we name social care--that countenances and develops care as an activity and set
      of relations lying at the intersection of state, market and family (and voluntary
      sector) relations. We are especially concerned to examine what the concept of
      social care can tell us about welfare state variation and welfare state change
      and development. The article works systematically through these themes, beginning
      with a brief historical sketch of the concept of care and then moving on to
      elaborate the analytic potential of the concept of social care. In the latter
      regard we make the case that it can lead to a more encompassing analysis, helping
      to overcome especially the fragmentation in existing scholarship between the cash
      and service dimensions of the welfare state and the relative neglect of the
      latter. The concept of social care serves to shift the centre of analysis from
      specific policy domains so that instead of focusing on cash benefits or services
      in isolation it becomes possible to consider them as part of a broader set of
      inter-relating elements. In this and other regards, the concept has the potential
      to say something new about welfare states.

PMID- 10905002
TI  - Technology and social interaction: the emergence of 'workplace studies'.
AB  - Despite the substantial body of literature concerned with the ways in which
      digital media are transforming contemporary society and institutional life, we
      have relatively little understanding of the ways in which new technologies
      feature in day to day organizational conduct and interaction. There is however a
      growing corpus of empirical research which places the situated and contingent
      character of new technologies at the heart of the analytic agenda, but as yet,
      these studies are relatively little known within sociology. They include
      ethnographies of command and control centres, financial institutions, the news
      media, and the construction industry. They address the ways in which tools and
      technologies, ranging from paper documents through to complex multimedia systems,
      feature in work and collaboration. In this paper, we discuss these so-called
      'workplace studies' and consider their implications for our understanding of
      organizational conduct, social interaction and new technology.

PMID- 10905003
TI  - Subalterns of technopoly: brokering techno-power in academic sociology.
AB  - Drawing on responses to a small-scale sensitizing sociological probe of
      'technological stratification' in academic sociology, this article considers the
      role of academic staff delegated to oversee the distribution of information and
      communications technology resources within their departments between the years
      1987-1996. From their recollections as local 'gatekeepers' of the new knowledge
      technologies, these 'subalterns of Technopoly' perceived themselves as relatively
      powerless 'techno-power brokers' unable to make a significant difference to the
      'technological stratification' they encountered in their working environments in
      that period.

PMID- 10905004
TI  - Consumerism, disorientation and postmodern space: a modest test of an immodest
      theory.
AB  - There has recently been an explosion of theoretical literature on social space. A
      central claim in this literature is that postmodern spaces are experienced as
      confusing or disorienting by human subjects. This claim remains untested. The
      paper reports results from a small-scale survey conducted in one form of
      postmodern space--the shopping mall. It suggests that unsupported assertions
      about the disorienting effects of postmodern space and their associated influence
      on consumerist activities should be treated with scepticism. Through practice
      humans are able to develop routines which enable them to competently navigate
      these spaces.

PMID- 10905005
TI  - Is it a different world to when you were growing up? Generational effects on
      social representations and child-rearing values.
AB  - In this paper, I explore the way in which people view how the world has changed
      since they were growing up. This is done both quantitatively and qualitatively,
      using open-ended responses from the British Household Panel Survey. The
      theoretical perspective draws on Mannheim's insight that generational location
      predisposes individuals to characteristic modes of thought and experience and
      Moscovici's contention that generations may have distinctive social
      representations. The data largely support the generational hypothesis. The ten
      most frequent changes mentioned are unemployment, lack of safety, lack of
      discipline, increased pressure, moral decline, increased crime, drugs,
      environmental problems, and family breakdown. These social representations of how
      the world has changed are significant predictors of child-rearing values,
      especially for women. More generally, I argue that despite the broad consensus
      concerning the problems facing children born today, the social representations of
      men and women who grew up in different epochs exacerbate the value clash between
      generations.

PMID- 10905006
TI  - A hundred years of town planning and the influence of Ebenezer Howard.

PMID- 10905007
TI  - Injecting drug user on England's south coast dies with Clostridium novyi
      infection.

PMID- 10905008
TI  - Wound botulism in injecting drug user: second case in England.

PMID- 10905009
TI  - [Non-occupational postexposure prophylaxis to human immunodeficiency virus: a two
      sided sword?].

PMID- 10905010
TI  - [Evaluation of four rapid methods for the investigation of the toxigenic capacity
      of Clostridium difficile strains isolated in a selective medium].
AB  - BACKGROUND: Use of selective Clostridium difficile culture as a diagnostic method
      for C. difficile associated disease requires to prove the toxigenic ability of
      the isolates. Toxin B detection by cell culture assay after growing the
      microorganism in enriched broth is the standard method, but it delays the final
      diagnosis for 3-5 days. This study compares retrospectively four rapid techniques
      for detecting these toxigenic C. difficile strains. METHODS: 106 clinical
      isolates of C. difficile (72 toxigenic and 34 non-toxigenic), these and 16
      clinical strains of other species of Clostridium were investigated. The four
      methods were performed directly from colonies growing on solid agar. They were:
      a) cytotoxin detection in cell culture; b) two PCR amplifications of toxin A and
      toxin B, respectively, and c) toxin A detection by an immunoenzymatic method
      (VIDAS CDA2). All these procedures were completed within a normal working day.
      RESULTS: Only the 72 toxigenic C. difficile strains gave positive results by cell
      culture and PCR techniques (sensitivity and specificity: 100%). A total of 14 out
      of 49 toxigenic C. difficile strains showed negative results by the VIDAS assay
      in the first run, but all them were positive in repeated tests. CONCLUSIONS:
      Although all methods performed well, the cytotoxicity assay done directly on
      colonies growing in CCFA is a simple and rapid technique, and appears to be well
      suited for use in laboratories with access to cell cultures.

PMID- 10905011
TI  - [Simplified method for the processing of sputum in the diagnosis of
      tuberculosis].
AB  - OBJECTIVE: We evaluated a simplified method for processing three serial sputum
      samples as a single sample, and compare the results with those obtained when
      processing three samples individually. MATERIAL AND METHODS: During a 32-week
      period, we studied 867 sputum samples from 289 patients with pulmonary
      tuberculosis suspicious. Samples from 148 patients (n = 444) were processed by
      simplified method, and samples from 141 patients (n = 423) were processed by
      individually method. All cultures were processed by ESP Culture System II (Difco
      Laboratories, USA). RESULTS: Seven mycobacterium's strains were isolated by
      individually method. Simplified method detected another seven strains. In both
      cases, four strains were identified as Mycobacterium tuberculosis. Mean time to
      detection mycobacteria were 21.5 and 24 days for simplified and individually
      method, respectively. Cultures from 21 patients were contaminated (11 patients by
      simplified method and 10 patients by individually method). Mean time to detection
      contaminated cultures were 8 days and 7.5 days for simplified and individually
      method, respectively. CONCLUSION: Simplified method may be a useful alternative
      in laboratories that must handle increasing numbers of samples, without decline
      in diagnostic performance.

PMID- 10905012
TI  - [Evaluation of different clinical samples and cell lines in the isolation of
      enterovirus in pediatric patients].
AB  - BACKGROUND: To evaluate prospectively the efficacy of different clinical samples
      and cellular lines in the isolation of Enteroviruses from pediatric patients.
      METHODS: In the period july-1997 to july-1999 we analyze the samples of 102
      pediatric patients (< 2 years old) with an unknown febrile etiology syndrome.
      After the process of decontamination the samples were inoculated in the MRC-5,
      Hep-2 and Vero cell lines by the shell-vial assay. After 2-3 days of incubation
      the monolayers were stained by a monoclonal antibody against VP1; then the
      strains were identified as Poliovirus, ECHO-virus or Coxsacke by specific
      antibodies. RESULTS: 96 clinical samples were studied (45 pharyngeal swabs, 28
      feces, 13 cerebrospinal fluid, 5 bloods, 4 urines and one bronchoalveolar
      lavage). Enteroviruses were isolated in 48 patients (47%), corresponding to 60
      clinical samples (62.5%). The enteroviruses were isolated in 75.5% of pharyngeal
      swabs, 71.4% of feces, 30.7% of cerebrospinal fluid, one blood (20%) and the
      bronchoalveolar lavage. 28 patients presented simultaneously both pharyngeal and
      rectal swabs; in this group the use of both samples permitted the isolation of
      Enteroviruses in 26 cases (92.8%). Of 60 Enteroviruses, 59 (98.3%) were isolated
      in the MRC-5 cell line, 23 (38.3%) in the Hep-2, and 14 (23.3%) in the Vero; the
      MRC-5 demonstrated a significant difference in the isolation of Enteroviruses
      compared with the other cell lines. The Enteroviruses were identified as 30 (50%)
      ECHO-virus, 15 (25%) as Poliovirus vaccine, 12 (20%) could not to be identified
      and in 3 cases (5%) no growth of virus was detected in the culture. The MRC-5
      cell line was significatively superior to the other in the isolation of the
      different Enteroviruses. CONCLUSIONS: To obtain the maximum diagnostic efficacy
      in front a patient with a possible infection by Enteroviruses, is necessary to
      use different clinical samples, specially the more related to the infection focci
      (cerebrospinal fluid or blood). The MRC-5 cell line has been the most efficace in
      the isolation of Enteroviruses independently of the type of clinical sample or
      the viral genus. The shell-vial assay is a good method for the isolation and
      identification of Enteroviruses isolated from clinical samples.

PMID- 10905013
TI  - [Identification of yeast and sensitivity in vitro against different antifungal
      agents].
AB  - INTRODUCTION: The increasing incidence of Candida yeasts infections and its
      hospital and community repercussion (vaginal thrush), as well as the will to
      acquire the knowledge of the new antifungal that were launched to the therapeutic
      store, have motivated us to identify that type of yeasts from different sources,
      as well as to study their behaviour against the antifungal, using commercial
      procedures with easy clinical application. MATERIALS AND METHODS: An amount of
      317 Candida yeasts were identified through commercial procedures (CHROMagar
      Candida and Auxacolor): 108 vaginals, 138 from ICU newborn children and 71 from
      ICU adults, while the antifungal drug susceptibilities was done to 199 of the
      isolated ones using another commercial procedure (Fungitest). RESULTS AND
      CONCLUSIONS: Candida albicans is identified as the most frequent in both hospital
      and community samples (78.7 and 45.93%, respectively), followed by Candida
      glabrata (19.44 and 28.23%, respectively). The sensitivity to amphotericin B and
      to 5-flucytosine was very high in every studied group, while sensitivity to
      imidazole derivatives depends on the samples source (lower sensitivity in the ICU
      newborn isolated ones) and the species (C. glabrata is less sensitive than C.
      albicans).

PMID- 10905014
TI  - [Epidemiology of non-typhoid salmonellosis in a hospital in Pontevedra (1994
      1997)].
AB  - BACKGROUND: Since data on non-typhoidal salmonellosis in our health care area are
      scarce, we undertook an epidemiological study covering a four year period (1994
      1997). METHODS: Retrospective descriptive study carried out through review of the
      medical and clinical microbiologic records at Hospital Provincial de Pontevedra.
      Culture, isolation, identification, antibiotic susceptibility and
      serotypification were done according to usual Clinical Microbiology protocols.
      RESULTS: Along the period under study 459 cases of non-typhoidal salmonellosis
      were diagnosed. The relative incidence was higher among pediatric than adult
      patients. Between 1994-1996 top incidence was detected in August, while in 1997
      another maximum was found in April, closely related to climatic variations. The
      most frequent serogroup was D, with an increase in serogroup B since 1996. We
      found 16 different serotypes, being the more frequent in decreasing order
      Enteritidis (87.2%), Typhimurium (3.6%) and Hadar (2.3%). This distribution shows
      differences with regard to other national series covering a similar period of
      time. The more frequently detected antibiotic resistance was to ampicillin (39.0%
      strains), ampicillin-sulbactam (17.6%) and nalidixic acid (5.9%). Neither 3rd
      generation cephalosporines nor fluoroquinolones resistance was detected. Serotype
      Typhimurium was the most resistant. We found association between certain
      resistance patterns and serotypes Hadar, Paratyphi B and Typhimurium. Most
      diagnosed cases corresponded to acute gastroenteritis (95.6%). Patients under 3
      and over 69 suffered more frequently from extraintestinal salmonellosis.
      CONCLUSIONS: The high incidence of alimentary toxinfection due to Salmonella spp.
      in our area should warrant strict epidemiological surveillance programmes to
      detect sources of infection, evaluate sanitary control measures and use of
      antibiotics.

PMID- 10905015
TI  - [Rupture of the spleen due to infection].

PMID- 10905016
TI  - [Mediastinal mass and hemoptysis].

PMID- 10905017
TI  - [Ulcerated oral lesion in a Venezuelan patient].

PMID- 10905018
TI  - [Endocarditis caused by Saccharomyces cerevisiae on the prosthetic valve].

PMID- 10905019
TI  - [Acute gastroenteritis caused by urease positive Vibrio parahaemolyticus in an
      immunocompromised patient].

PMID- 10905021
TI  - [Amebic liver abscess of autochthonous origin: case report].

PMID- 10905020
TI  - [Update on antibiotic sensitive Streptococcus pyogenes in a pediatric
      population].

PMID- 10905022
TI  - [Age-dependent seroprevalence of Helicobacter pylori in children and adolescents
      in the community of Madrid].

PMID- 10905023
TI  - [Mycobacterium kansasii osteomyelitis in a patient infected by the human
      immunodeficiency virus].

PMID- 10905024
TI  - [Amplicor HIV-1 monitor and NucliSens HIV-1 QT: comparison of two new techniques
      to determine the viral load of the human immunodeficiency virus type 1].

PMID- 10905025
TI  - [Femur septic bursitis in a patient undergoing radiotherapy for cavum
      lymphoepithelioma].

PMID- 10905026
TI  - [Streptococcus agalactiae meningitis in an adult with cranio-encephalic trauma
      and neurosurgery].

PMID- 10905027
TI  - [What should be done for Acinetobacter baumannii infections?].

PMID- 10905028
TI  - [The desynchronization and synchronization of the adolescent EEG evoked by
      stimuli triggering or suppressing a sensorimotor reaction. II. Their
      characteristics in the attention-deficit and hyperactivity syndrome].

PMID- 10905029
TI  - [The perception of the emotional component of speech by stuttering children
      against a noisy background. I. An analysis of the efficiency in identifying
      different emotions].

PMID- 10905030
TI  - [The functional specialization of the hemispheres in matching current and
      preceding stimuli].

PMID- 10905031
TI  - [Interhemispheric asymmetry and the problem of the constancy of the visual
      perception of large and small sizes].

PMID- 10905032
TI  - [The biological bases for individual differences in infants in the 2nd half-year
      of life. II. The nature of the individual differences in temperament traits].

PMID- 10905033
TI  - [Short-latency auditory evoked potentials during a change in the physical
      parameter of a sound stimulus].

PMID- 10905034
TI  - [The effect of weak electromagnetic fields on the stability of a computer monitor
      image: the possible consequences for the operator].

PMID- 10905035
TI  - [The reflection of individual typological characteristics in the structure of the
      spatial interaction of EEG waves at different frequency ranges].

PMID- 10905036
TI  - [The clinical use of the transplantation of embryonic brain anlagen in the
      disease of epilepsy].

PMID- 10905038
TI  - [The temporal pattern of the controlling actions supporting the stabilization of
      human vertical posture].

PMID- 10905037
TI  - [The dynamics of transcutaneous oxygen and carbon dioxide tension during the
      performance of the normal ischemic test and under chronic ischemia of the
      extremities].

PMID- 10905039
TI  - [The physiological bases of the differences in body resistance to submaximal
      physical loading up to capacity in healthy young subjects].

PMID- 10905040
TI  - [The age-related characteristics of the organization of motor activity in 6- to
      16-year-old children].

PMID- 10905041
TI  - [The characteristics of the cardiac activity in 5- to 7-year-old children under
      loads of different capacities].

PMID- 10905043
TI  - [The reaction characteristics of the endocrine and cardiovascular systems in
      persons with different types of temperament to emotional stress].

PMID- 10905042
TI  - [The functional study of the motor system and of the central blood circulation in
      7- to 12-year-old girls with different levels of physical training].

PMID- 10905044
TI  - [Biological trials of physiologically active compounds (the methodology). II].

PMID- 10905045
TI  - [In Process Citation]

PMID- 10905046
TI  - [The interhemispheric differences in cortical evoked activity during computer
      work training].

PMID- 10905047
TI  - [The blood and urine spectral indices in the dynamics of acute alcoholic
      psychoses].

PMID- 10905048
TI  - Homeobox genes in leukemogenesis.
AB  - Considerable progress has been made in unraveling key pathogenetic steps in human
      leukemogenesis. In recent years, cytogenetic analyses and the molecular
      characterization of chromosomal breakpoints in patients with acute leukemia have
      proven that homeobox (HOX) genes, an evolutionarily highly conserved family of
      transcription factors, are critically involved in human leukemogenesis. HOX genes
      themselves, as well as their upstream regulators and cofactors, are implicated in
      the pathogenesis of leukemia, and experimental models using knock-in strategies
      or retrovirally induced overexpression of candidate genes have shown the
      leukemogenicity of homeobox genes. This review summarizes the recent advances in
      this field.

PMID- 10905050
TI  - Pathophysiology and treatment of thrombotic thrombocytopenic purpura/hemolytic
      uremic syndrome (TTP/HUS).
AB  - The central pathogenic feature of thrombotic thrombocytopenic purpura/hemolytic
      uremic syndrome (TTP/HUS) is the formation of platelet aggregates, perhaps by
      damaged endothelial cells. The evidence for endothelial cell damage has been
      supported by multiple findings, including the harmful effects of TTP/HUS plasma,
      which induces endothelial cell apoptosis. Ultra-large multimers of von Willebrand
      factor (vWf), which activates platelets, are found in TTP/HUS patients,
      presumably after being released into circulation from damaged endothelial cells.
      It has been reported that loss or dysfunction of the vWf-cleaving protease is
      related to the development of acute or chronic TTP/HUS. Detection of platelet
      activation in TTP/HUS patients, which previously had been difficult, is now
      possible with a particle-counting technique using light scattering. TTP/HUS
      occurring after bone marrow transplantation (BMT), similar to that in classic
      TTP/HUS, appears to represent a separate facet of the disease. We observed that
      BMT-TTP/HUS might be predicted at an early stage by determining any increase in
      plasma interleukin-12 at the time of leukocyte recovery. It is known that plasma
      treatment is effective for TTP/HUS patients; we found that a high-molecular
      weight fraction (HMW-F) of plasma is effective in treating chronic TTP/HUS
      patients. HMW-F of plasma may contain the main factor necessary for improvement
      of TTP/HUS syndrome.

PMID- 10905049
TI  - Janus kinases (JAKs) and signal transducers and activators of transcription
      (STATs) in hematopoietic cells.
AB  - Hematopoietic cell growth and differentiation are controlled by a number of
      cytokines. Ligand stimulation induces rapid phosphorylation of the tyrosine
      residues of the cytokine receptor and a variety of cellular molecules. Among
      them, Janus kinases (JAKs) and signal transducers and activators of transcription
      (STATs) have recently been found to play a unique role in cytokine receptor
      mediated intracellular signaling and hematopoietic cell development. Abnormal
      signaling of the JAK-STAT pathway results in hematopoietic disorders, including
      severe combined immunodeficiency and leukemia.

PMID- 10905051
TI  - Granulocyte colony-stimulating factor and lineage-independent modulation of VLA-4
      expression on circulating CD34+ cells.
AB  - Although the use of allogeneic transplants of peripheral blood stem/progenitor
      cells (PBSCs) is increasing, the precise mechanism of PBSC mobilization has not
      yet been fully clarified. We examined the expression of some adhesion molecules
      on CD34+ cells from steady-state bone marrow (BM), granulocyte colony-stimulating
      factor (G-CSF)-mobilized PBSCs, and cytotoxic drugs plus G-CSF-mobilized PBSCs.
      Irrespective of mobilization method, very late antigen (VLA)-4 expression on
      circulating CD34+ cells was significantly lower than on steady-state BM CD34+
      cells. To elucidate the influence of lineage commitment on VLA-4 expression of
      circulating CD34+ cells, we analyzed VLA-4 expression on different subsets of
      CD34+ cells with or without CD33, CD38, CD5, or CD10 antigens, or Glycophorin A
      in G-CSF-mobilized PBSCs and steady-state BM from related donors, using 3-color
      flow cytometry. VLA-4 on circulating CD34+ subsets was less expressed than on
      each corresponding subset of steady-state BM CD34+ cells. Furthermore, VLA-4
      positive rates showed no significant difference among the CD34+ subsets. Finally,
      the data comparing CD34+ cells from steady-state and G-CSF-mobilized PBSCs
      revealed no differences in terms of VLA-4 expression. These data suggest that
      reduced expression of VLA-4 may be a result of peripheralization of CD34+ cells
      from bone marrow, which occurs in a G-CSF- and lineage-independent fashion.

PMID- 10905052
TI  - Down-regulation of human telomeric protein TRF1 gene expression during myeloid
      differentiation in human hematopoietic cells.
AB  - The maintenance of telomere length is crucial for cell survival. Recently, it has
      been indicated that the human telomeric protein TRF1 is involved in the negative
      feedback mechanism that stabilizes telomere length. We studied TRF1 mRNA
      expression in hematopoietic cells to clarify the relation between TRF1 and
      telomerase by semiquantitative reverse transcriptase-polymerase chain reaction.
      In polymorphonuclear cells and monocytes isolated from peripheral blood,
      relatively low levels of TRF1 mRNA expression were seen, compared with those of
      lymphocytes and CD34+. We then assessed TRF1 mRNA expression in CD34+ cells
      cultured in vitro with growth factors. After 4 weeks of culture, all the cells
      showed myeloid differentiation, and telomerase activity was down-regulated. TRF1
      mRNA was expressed in CD34+ cells but was down-regulated in cells cultured for 4
      weeks. We conclude that TRF1 mRNA expression is down-regulated in accordance with
      telomerase down-regulation during the course of myeloid differentiation.

PMID- 10905053
TI  - Glucocorticoid-induced apoptotic pathways in eosinophils: comparison with
      glucocorticoid-sensitive leukemia cells.
AB  - Glucocorticoids are known to promote apoptosis of eosinophils, normal and
      neoplastic lymphoid cells, and blastic cells in some patients with acute myeloid
      leukemia. We investigated the biochemical signal transduction pathways, in
      particular, the generation of reactive oxygen species (ROS) and activation of
      caspases in dexamethasone (DEX)-induced apoptosis of eosinophils, and we compared
      them with those in DEX-sensitive myeloid and lymphoid leukemia cell lines. The GC
      receptor antagonist completely abolished DEX-induced apoptosis of eosinophils and
      leukemia cells. Among inhibitors related to the ROS system, diphenylene iodonium
      (DPI), a nicotinamide adenine dinucleotide diphosphate (NADPH) oxidase inhibitor,
      strongly inhibited both spontaneous and DEX-induced apoptosis of eosinophils at
      concentrations as low as 0.2 to 2 mumol/L, while promoting apoptosis of leukemia
      cells in a dose-dependent manner. Apocynin, another NADPH oxidase inhibitor, and
      antioxidants did not affect the apoptosis of eosinophils or leukemia cells. DEX
      treatment did not change intracellular production of O2- and H2O2, and it
      decreased the extracellular release of O2- in both cells. These results suggest
      little or no involvement of ROS generation in DEX-induced apoptosis of both
      cells. Although among peptide-based caspase inhibitors, only z-VAD-FMK, a broad
      caspase inhibitor, partially inhibited the apoptosis of eosinophils and leukemia
      cells, DEX treatment increased the activities of caspases 2-, 3-, 6-, and 8-like
      proteases assessed by colorimetry in both cells, suggesting the involvement of a
      similar caspase activation pathway in DEX-induced apoptosis in both cells. DPI
      markedly reduced caspase 3-like activity in eosinophils, while augmenting the
      activity in leukemia cells, indicating that DPI acts upstream of caspase 3
      activation opposingly in both cells. Thus, the action of DPI in eosinophils seems
      peculiar in respect to apoptosis induction, and DPI appears to exert an influence
      on unknown targets rather than those involved in NADPH oxidase inhibition.

PMID- 10905054
TI  - Aplastic anemia is associated with HLA-DRB1*1501 in northern Han Chinese.
AB  - It has been reported that aplastic anemia (AA) is more common in HLA-DR2-positive
      individuals than in the general population. We investigated the frequency of some
      HLA loci of 102 Northern Han Chinese patients with AA and 105 healthy control
      subjects. Polymerase chain reaction and sequence specific oligonucleotide probe
      hybridization were used to determine HLA-DR- and HLA-DR2-related DRB1 alleles.
      The frequency of DR2 is increased in AA patients; the relative risk (RR) was
      2.86, and the difference was significant (chi 2 = 11.1, P = .004). The RR of HLA
      DRB1*1501 was 3.07, and the difference was significant (chi 2 = 9.42, P = .008).
      The above results suggest that HLA-DR2 is significantly associated with AA in
      Northern Han Chinese. HLA-DRB1*1501 is the main subtype of HLA-DR2, and may be
      the susceptibility gene of AA.

PMID- 10905055
TI  - Morphological and cytogenetic changes in therapy-related leukemia developed in a
      t(8;21)-acute myeloid leukemia (M2) patient: sequential cytogenetic and molecular
      analyses.
AB  - A patient with acute myeloid leukemia (AML)-M2 with t(8;21)(q22;q22) achieved
      complete remission with remission-induction chemotherapy followed by
      consolidation and intensification chemotherapies. T(8;21)(q22;q22) disappeared,
      but chimeric AML1/MTG8 was continuously detected in bone marrow cells. Following
      the development of therapy-related leukemia after 1 year, evolution of therapy
      related AML-M4 with t(11;17)(q23;q25) and the rearrangement of the MLL gene were
      observed, while AML/MTG8 disappeared. After reinduction and following
      intermittent chemotherapies, a subsequent alternative transformation to AML-M2
      occurred after detection of t(3;21)(q21;q22), with a break in the AML1 gene shown
      by interphase fluorescence in situ hybridization analysis. This leukemia
      transformed to AML-M4 after t(9;22)(q34;q11), with a minor BCR/ABL rearrangement,
      and then finally to AML-M2. This therapy-related leukemia was resistant to
      chemotherapy. These findings indicate that alterations in cytogenetic and
      molecular events caused by chemotherapeutic agents contribute to the sequential
      evolution of new leukemic clones with different morphology.

PMID- 10905056
TI  - Secondary near-pentaploidy and/or near-tetraploidy characterized by the
      duplication of 8;21 translocation in the M2 subtype of acute myeloid leukemia.
AB  - Hyperploidy, especially near-tetraploidy, is rare in acute myeloid leukemia
      (AML). We report 2 cases with secondary hyperploidy characterized by double 8;21
      translocations. Morphologic observation of bone marrow smears revealed numerous
      giant blasts in both cases. Chromosome analyses with R-banding technique showed a
      karyotype of 46,XX,t(8;21)(2%)/92,XXXX, add(7)(q31)x2,t(8;21)x2(7%)/100-117,XXX,
      X,-X,-1,+4,+4,-7,+add(7)(q31)x3 ,
      t(8;21)x2,+der(21)t(8;21),+22(90.6%)/46,XX(0.3%) in case 1 and a karyotype of
      45,X,-Y,t(8;21)(15%)/90,XX,-Y,-Y,t(8;21)x2(80%)/46,XY(5%) in case 2. DNA ploidy
      analyses by flow cytometry showed triple peaks (diploid, tetraploid [DI 2.09] and
      near-pentaploid [DI 2.59]) in case 1, and double peaks (diploid and near
      tetraploid [DI 2.07]) in case 2. Reverse-transcriptase polymerase chain reaction
      detected an AML1/ETO fusion transcript (152 bp) in both cases. This paper brings
      the total number of cases of secondary hyperploid t(8;21) AML to 6 and further
      emphasizes a correlation between hyperploidy and t(8;21) translocation.

PMID- 10905057
TI  - Treatment with low-dose cytosine arabinoside followed by administration of
      macrophage colony-stimulating factor prolongs the survival of patients with RAEB,
      RAEB-T, or leukemic phase myelodysplastic syndrome: a pilot study.
AB  - The treatment of patients with aggressive subclasses of myelodysplastic syndrome
      (MDS) remains a challenge. In an effort to improve the survival of patients with
      refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-t), or
      acute myelogenous leukemia transformed from MDS (MDS-AML), we conducted a small
      trial in which 28 such patients were treated with low-dose cytosine arabinoside
      (LDAraC) followed by administration of macrophage colony-stimulating factor (M
      CSF). The overall rate of response to the treatment was 61%, including 39% with a
      complete response, which is higher than rates obtained in previous studies in
      which LDAraC alone was administered to patients with MDS. Median survival was
      23.5 months in cases of RAEB, 16.7 months in cases of RAEB-t, and 19.7 months in
      cases of MDS-AML. The overall survival of the study group appeared to be
      prolonged in comparison with a historical control group of patients treated with
      LDAraC alone. It is suggested that M-CSF added to the administration of LDAraC
      plays an active role in the therapy. No therapy-related death occurred. Some
      unique actions of M-CSF were suggested in this trial. It is concluded that
      therapy with LDAraC + M-CSF is a useful treatment option for patients with
      aggressive subclasses of MDS and MDS-AML to provide better response and survival.

PMID- 10905058
TI  - Expression of B cell-associated transcription factors in B-cell precursor acute
      lymphoblastic leukemia cells: association with PU.1 expression, phenotype, and
      immunogenotype.
AB  - B-lymphocyte development progresses through discrete stages characterized by
      regular DNA rearrangements of the immunoglobulin (Ig) loci that lead to the
      transcription of Ig genes and expression of B-cell antigen receptors. These
      developmental processes can also be distinguished by the expression of specific
      cell-surface markers. Therefore, rearrangement of the Ig, T-cell receptor (TCR)
      genes, and surface markers are generally considered as useful markers of the B-
      and T-cell lineage in lymphoproliferative disorders. However, concomitant
      rearrangement of Ig and TCR genes (double genotype) has been reported in the most
      immature lymphoid malignancies (lineage promiscuity), mainly in B-cell precursor
      acute lymphoblastic leukemia (pre-B ALL), but the mechanism is not fully
      understood. DNA rearrangements and specific cell-surface markers are regulated by
      several specific transcription factors. To better characterize the lineage
      promiscuity, we studied the relationship among the expression of lymphoid
      associated transcription factors, phenotype, and immunogenotype. Rearrangement of
      the Ig light chain kappa gene was found in 37% of pre-B ALL samples and in all B
      cell chronic lymphocytic leukemia (B-CLL) samples. Rearrangement of TCR gamma
      gene was shown in 40% of pre-B ALL samples but was not detected in any of the B
      CLL samples. Among the tested B cell-associated transcription factors, Pax5 and
      E47 genes were expressed in all pre-B ALL and B-CLL samples. RAG-1 gene was
      expressed in all pre-B ALL samples but not in the B-CLL samples. Oct-2 gene was
      expressed in 82% of pre-B ALL and all B-CLL samples. The expression of PU.1 gene
      was shown in 56% of pre-B ALL but not in the B-CLL samples. Interestingly, the
      samples of pre-B ALL, which did not express the PU.1 gene, showed a significantly
      high frequency of TCR gamma gene rearrangement. This phenomenon was not found
      with Oct-2 gene expression. These findings suggest that absence of PU.1
      expression may result in lineage promiscuity, such as the simultaneous
      rearrangements of Ig and TCR genes in pre-B ALL cells.

PMID- 10905059
TI  - Cytotoxic T-cell lymphoma diffusely involving the entire gastrointestinal tract
      associated with Epstein-Barr virus and tubercle bacilli infection.
AB  - We describe a rare case of cytotoxic gastrointestinal T-cell lymphoma with
      protein-losing enteropathy. Initial examination revealed the coexistence of T
      cell lymphoma and tuberculosis in the mesenteric lymph node and liver. Despite
      anti-tuberculosis and anti-cancer treatment, the patient experienced chronic
      diarrhea and malabsorption and died approximately 3 years after onset. Autopsy
      specimens revealed medium-sized lymphoma cells, with a phenotype of CD3+, CD4-,
      CD7+, CD8+, CD30-, CD56-, CD103 (HML-1)-, TIA-1+, and granzyme B+, proliferating
      primarily and consistently in the mucosa of the entire bowel tract from esophagus
      to rectum. Interestingly, Epstein-Barr virus (EBV)-encoded small nuclear RNAs
      were detected in the tumors by in situ hybridization. Southern blot analysis
      revealed monoclonal proliferation in the EBV-infected T cells. Although the
      present case can possibly be categorized as an intestinal T-cell lymphoma
      according to the Revised European-American Lymphoma Classification, the case
      showed a unique clinical course and distribution of lymphoma cells. We present
      here an interesting case of gastrointestinal cytotoxic T-cell lymphoma and
      examine the possible association with infectious agents.

PMID- 10905060
TI  - Successful graft-versus-leukemia effect of second bone marrow transplantation on
      relapsed leukemia cutis that was refractory to intensive chemotherapy and donor
      lymphocyte transfusions in a patient with acute monocytic leukemia.
AB  - We report a patient with acute monocytic leukemia (AMoL; M5) who received a
      second bone marrow transplantation (BMT) with graft-versus-leukemia (GVL) effect
      on relapsed leukemia cutis, which had been refractory to intensive chemotherapy
      and donor lymphocyte transfusions (DLTs). A 21-year-old woman was diagnosed with
      AMoL and achieved complete remission after intensive chemotherapy. The patient
      received a nonmanipulated allogeneic BMT from her HLA-identical father. Skin
      tumors developed in her upper extremities, chest, and thigh 11 months after BMT.
      Leukemia cutis was confirmed by skin biopsy. There was no evidence of relapse in
      bone marrow. The patient received several courses of chemotherapy and DLTs for
      the skin relapse, but the skin tumors persisted. The patient then received a
      second BMT from the same donor. On day 80, grade II acute graft-versus-host
      disease developed, and the remaining skin tumors were eradicated on day 98, most
      probably because of GVL effect.

PMID- 10905061
TI  - Proliferation of CD4+ lymphocytes in a patient with chronic graft-versus-host
      disease after allogeneic bone marrow transplantation.
AB  - Expansion of donor-derived lymphocytes after allogeneic stem cell transplantation
      is a serious and sometimes fatal complication. Lymphoproliferative disorders are
      reportedly caused mainly by reactivation of Epstein-Barr virus (EBV) and non-EBV
      associated secondary lymphoma or leukemia. In this paper, we report massive
      proliferation of CD4+ lymphocytes in peripheral blood of a patient with chronic
      graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation
      (alloBMT) from an HLA-identical sibling donor. The abnormal lymphocytes showed
      CD3low, CD4+, CD8-, CD2+, CD5+, CD7+, CD25-, CD19-, CD20-, CD21-, CD16-, CD56low,
      T-cell receptor (TCR)-alpha/beta- and TCR-gamma/delta- phenotypes, and no
      rearrangement of either TCR-C beta 1 or IG(H)JH was detected from the lymphocytes
      by Southern blot analysis. EBV was not found in the nuclei of lymphocytes by an
      immunofluorescence antibody. The lymphoproliferation was resistant against
      immunosuppressive drugs, administered for the treatment of chronic GVHD, and it
      effectively inhibited aggravation of the chronic GVHD. Although antithymocyte
      globulin and cytosine arabinoside were administered later, the patient died of
      respiratory failure with bilateral pleural effusion and interstitial pneumonia.
      Because we found no evidence of monoclonality of the abnormal lymphocytes, we
      could not conclude that this patient had suffered from malignant
      lymphoproliferation. To our knowledge, this is the first case report of
      proliferation of CD4+ lymphocytes in a patient with chronic GVHD following
      alloBMT. In this paper, we discuss the possible pathophysiology of the patient.

PMID- 10905062
TI  - Massive pericardial and pleural effusion with anasarca following allogeneic bone
      marrow transplantation.
AB  - A 10-year-old girl presented with massive pericardial/pleural effusion with
      anasarca 216 days after an allogeneic bone marrow transplantation from her HLA
      matched sibling for relapsed acute lymphoblastic leukemia. She did not show any
      other symptoms of chronic graft-versus-host disease (GVHD). The antinucleolar
      antibody was elevated in the blood and the pleural fluid. The lymphocytes in the
      fluid were mostly CD8+/HLA-DR+, and a majority of CD8+ cells in the blood
      expressed CD57. These data suggested that she had chronic GVHD. Immunosuppressive
      therapy including prednisolone, cyclosporin A, high-dose methylprednisolone,
      tacrolimus (FK506), and methotrexate had no effect, and the patient died of
      Aspergillus pneumonia 183 days after the presentation of the disease. Although it
      has not been described before, isolated serositis with edema should be recognized
      as a clinical feature of chronic GVHD.

PMID- 10905064
TI  - What is the difference between May-Hegglin anomaly and Sebastian platelet
      syndrome?

PMID- 10905063
TI  - The role of screening bronchoalveolar lavage in BMT patients.

PMID- 10905065
TI  - Persistent endemicity of Gymnophalloides seoi infection in a southwestern coastal
      village of Korea with special reference to its egg laying capacity in the human
      host.
AB  - Follow-up studies have been conducted every three years on the endemicity of
      Gymnophalloides seoi infection in a small coastal village of Chollanam-do
      (Province), Korea, since it was first known as an endemic area in 1994. Special
      attention was given to its egg laying capacity in the human host. In fecal
      examinations, the overall helminth egg and/or cyst positive rate was 78.7%
      (74/94) in 1997 and 76.6% (82/107) in 2000. Among them G. seoi eggs showed the
      highest rate; 71.3% (67/94) in 1997 and 72.0% (77/107) in 2000. The average
      number of eggs per gram of feces (EPG) was 1,015 in 1997, while a reduced rate of
      353 was observed in 2000. In 1997, total of 320,677 adult flukes of G. seoi (av.
      10,344/person, 94-69,125 in range) were collected from the diarrheic stools of 31
      treated patients. The EPG/worm obtained from 21 cases ranged from 0.04 to 0.77
      (av. 0.23), suggesting density-dependent constraints on the worm fecundity. The
      relationship between the worm burden (X) and EPG/worm (Y) can be expressed as Y =
      0.42.e-1.2 chi (r = 0.49). The results showed that G. seoi infection is
      persistently endemic in this village.

PMID- 10905066
TI  - In vitro infection of Cryptosporidium parvum to four different cell lines.
AB  - To determine a suitable condition for in vitro infection model of Cryptosporidium
      parvum, four different cell lines, AGS, MDCK, HCT-8 and Caco-2, were used as host
      cell lines which were cultured at various concentrations of added supplements.
      These supplement include fetal bovine serum (FBS), sodium choleate, ascorbic
      acid, folic acid, calcium pantothenate, para-aminobenzoic acid and pyruvate and
      their effects on the cell lines which were infected with C. parvum were
      evaluated. The results of this study showed that the AGS cell line was most
      susceptible to C. parvum whereas the Caco-2 cells appeared to be least
      susceptible to C. parvum. In regards to the serum condition, 10% FBS was suitable
      for the growth of AGS and HCT-8 cells, and 1% FBS was good for the growth of the
      MDCK cells when they were inoculated with C. parvum. Vitamins had a positive
      effect on the AGS cells, and pyruvate also showed positive effects on all of the
      cell lines except for Caco-2. Modified medium for each cell line was prepared by
      adding appropriate amounts of each supplement which resulted in the highest
      parasite infection number. Modified media increased the number of parasites
      infected on AGS cells to 2.3-fold higher when compared to the control media. In
      this study, we found that the AGS cell line was a suitable host model for
      evaluating C. parvum in vitro study and the media contents for the optimal
      infection conditions were suggested.

PMID- 10905067
TI  - Non-specific activation of mouse peritoneal macrophages by a freshwater ciliate,
      Tetrahymena pyriformis.
AB  - Toxoplasma-killing activities of mouse peritoneal macrophages activated by the
      extracts of Tetrahymena pyriformis (Korean and Chinese strains) were evaluated,
      and the active protein fractions from both strains were partially characterized
      by a method including chromatographies and SDS-PAGE. The first peak in Korean
      strain and the second peak in Chinese strain of T. pyriformis obtained by DEAE
      Sephadex A-50 chromatography were most effective in the activation of macrophages
      to kill Toxoplasma gondii tachyzoites in vitro. Subsequent fractionations of
      obtained peak fractions were performed on a Sephadex G-200 gel. The first peaks
      fractionated from both strains of T. pyriformis had the highest toxoplasmacidal
      activities, and when subjected to the SDS-PAGE, one prominent band was visualized
      for each of the strains showing the same molecular weight of ca. 52.6 kDa. This
      active protein is suggested to be related to non-specific activation of mouse
      peritoneal macrophages.

PMID- 10905068
TI  - Persisting antibody reaction in paragonimiasis after praziquantel treatment is
      elicited mainly by egg antigens.
AB  - Antibody responses in serum and cerebrospinal fluid (CSF) samples from patients
      with active and chronic paragonimiasis and in sera from patients on whom follow
      up studies were done after praziquantel treatment were analyzed using antigens of
      Paragonimus westermani prepared from eggs, metacercariae, juveniles of 4- and 7
      week old, adult worms and recombinant protein of 28 kDa cruzipain-like cysteine
      protease (rPw28CCP). The patient sera/CSFs of active and chronic paragonimiasis
      revealed strong antibody reactions against the crude extracts of 4- and 7-week
      old juveniles as well as against those from egg and adult. rPw28CCP also showed
      specific reaction to the sera with active paragonimiasis. After the treatment,
      levels of specific antibodies in the sera gradually decreased to negative range
      in most patients. In some cases with persisting high antibody levels, however,
      the reactions at 27 kDa egg protein were sustained throughout the observation
      period of 34 months. The reactions at 35 and 32 kDa in adult extract and rPw28CCP
      disappeared rapidly after the treatment. Persistent antibody reactions even after
      successful treatment are provoked by continuous antigenic challenge from eggs
      which were not resolved by treatment.

PMID- 10905069
TI  - Sequential analysis of cell differentials and IFN-gamma production of splenocytes
      from mice infected with Toxoplasma gondii.
AB  - To assess the relationship between the changes of cellular components and the
      production of Th1 cytokine in the immune tissue, inbred C57BL/6 mice were orally
      infected with 40 cysts of 76K strain of Toxoplasma gondii. The sequential change
      of cell differentials and IFN-gamma production of splenocytes were analyzed by
      Diff-Quik stain and RT-PCR. There were no significant proportional changes of
      cellular components of splenocytes until day 4 postinfection (PI) as compared to
      those of day 0, and the relative percentage of macrophages and
      neutrophils/eosinophils increased significantly (p < 0.01) thereafter. The
      expression of IFN-gamma mRNA of CD3- cells was observed from day 1 PI at a low
      level. However, IFN-gamma production of CD3+ cells increased significantly from
      day 4 PI (p < 0.01) which progressively increased thereafter. These findings
      provide the relative percentages of granulocytes and macrophages were increased
      in conjunction with increase of total number of splenocytes after oral infection
      with T. gondii in the susceptible murine hosts, and lymphocytes were the major
      cellular components and the important source of IFN-gamma.

PMID- 10905070
TI  - Seroprevalence of toxoplasmosis in the residents of Cheju island, Korea.
AB  - This study was performed to evaluate the epidemiological status of toxoplasmosis
      among the residents of Cheju island. The sera of local students from 18 high
      schools (boys 2110, girls 2460) and those of adults (474 admitted to Cheju
      Chungang General Hospital) were collected and checked for the IgG antibody titers
      against Toxoplasma gondii. Serum samples collected from both the students and
      adults showed sero-positive rate of 5.5% and 12.9%, respectively. Although the
      rates were not significantly different between the sexes (5.4% for the boys and
      5.5% for the girls attending school), the geographical difference showed a
      significant difference between the urban (4.6-6.9%) and rural areas (5.6-8.8%) (p
      < 0.05). Based on the high positive rates, it should be necessary to control
      toxoplasmosis in Cheju island.

PMID- 10905071
TI  - Partial characterization of a 17 kDa protein of Clonorchis sinensis.
AB  - A 17 kDa protein from Clonorchis sinensis adults was purified by a procedure
      including Sephacryl S-200 HR gel filtration and Q-Sepharose anion exchange
      chromatography. The protein was proved to be a cysteine protease as it showed
      hydrolytic activity toward Cbz-Phe-Arg-AMC in the presence of dithiothreitol and
      was inhibited by specific inhibitors such as iodoacetic acid or trans epoxy
      succinly-L-leucyl-amido(4-guanidino) butane. The polyclonal antibody raised
      against the protein reacted to 17 kDa proteins of trematodes such as Paragonimus
      westermani, Fasciola hepatica, Opisthorchis viverrini, Gymnophalloides seoi, and
      Metagonimus yokogawai. The antibody recognized the 17 kDa and 16 kDa cysteine
      proteases purified from C. sinensis, P. westermani, and G. seoi as well. These
      results suggest that the 17 kDa protein may be a cysteine protease commonly
      present in trematodes.

PMID- 10905072
TI  - In vitro cytotoxicity of Acanthamoeba spp. isolated from contact lens containers
      in Korea by crystal violet staining and LDH release assay.
AB  - In order to observe the cytotoxicity of Acanthamoeba spp., which were isolated
      from contact lens containers as ethiological agents for the probable amoebic
      keratitis in Korea, the crystal violet staining method and LDH release assay were
      carried out. In the crystal violet staining method, among eight contact lens
      container isolates, isolate 3 (Acanthamoeba KA/LS5) showed 83.6% and 81.8% of
      cytotoxicity, and isolate 7 (Acanthamoeba KA/LS37) showed 28.2% and 25.1% of
      cytotoxicity, in 1 mg/ml and 0.5 mg/ml lysate treatments, respectively.
      Acanthamoeba culbertsoni and A. healyi showed 84.0% and 82.8% of cytotoxicity.
      Similar results were observed in A. castellanii and A. hatchetti which showed
      83.6% and 75.5% of cytotoxicity. Acanthamoeba royreba and A. polyphaga showed
      9.0% and 1.7% of cytotoxicity. In the LDH release assay, isolate 3 (20.4%) showed
      higher cytotoxicity than other isolates in 1 mg/ml lysate treatment. The results
      provide that at least isolate 3 has the cytotoxic effect against CHO cells and
      seems to be the pathogenic strain.

PMID- 10905073
TI  - Excretory-secretory product of Paragonimus westermani newly excysted
      metacercariae inhibits superoxide production of granulocytes stimulated with IgG.
AB  - It is well known that the cysteine proteases in excretory-secretory product (ESP)
      of Paragonimus westermani newly excysted metacercariae (PwNEM) are capable of
      degrading IgG in vitro. Recent evidence suggests that the IgG-coated surface,
      such as found on parasites, is one of the most effective physiologic stimuli for
      granulocyte activation. Therefore, this study was designed to investigate the
      effect of excretory-secretory product (ESP) of PwNEM on superoxide production of
      granulocytes stimulated with IgG. The 96-well plates were coated with human IgG
      (0, 10, 30, 100 micrograms/ml) in the absence or presence of ESP. When
      granulocytes were incubated in the wells coated with human IgG in the presence of
      ESP, the level of superoxide production of granulocytes was reduced to about 90%
      when compared to the cells incubated in the wells coated with IgG alone. This
      inhibitory effect of the ESP on IgG-induced superoxide production of granulocytes
      was concentration-dependent. These results suggest that ESP secreted by PwNEM may
      be important in the control of effector functions of granulocytes stimulated with
      IgG in human paragonimiasis.

PMID- 10905074
TI  - A role of carboxy-terminal region of Toxoplasma gondii-heat shock protein 70 in
      enhancement of T. gondii infection in mice.
AB  - We investigated the role of recombinant Toxoplasma gondii heat shock protein
      (rT.g.HSP) 70-full length, rT.g.HSP70-NH2-terminal region, or rT.g.HSP70-carboxy
      terminal region in prophylactic immunity in C57BL/6 mice perorally infected with
      Fukaya cysts of T. gondii. At 3, 4, 5, and 6 weeks after infection, the number of
      T. gondii in the brain tissue of each mouse was measured by quantitative
      competitive-polymerase chain reaction (QC-PCR) targeting the surface antigen
      (SAG) 1 gene. Immunization with rT.g.HSP70-full length or r.T.g.HSP70-carboxy
      terminal region increased the number of T. gondii in the brain tissue after T.
      gondii infection, whereas immunization with rT.g.HSP70-NH2-terminal region did
      not. These results suggest that T.g.HSP70-carboxy-terminal region as well as
      T.g.HSP70-full length may induce deleterious effects on the protective immunity
      of mice infected with a cyst-forming T. gondii strain, Fukaya.

PMID- 10905075
TI  - The first human case of Trichinella spiralis infection in Korea.
AB  - Three cases of human infection by Trichinella spiralis were first confirmed by
      detecting encysted larvae in the biopsied muscle in December 1997, in Korea. The
      patients were one 35- and two 39-year-old males residing in Kochang-gun,
      Kyongsangnam-do. They had a common past history of eating raw liver, spleen,
      blood and muscle of a badger, Meles meles melanogenys, and complained of high
      fever, facial and periorbital edema, and myalgia. Hematologic and biochemical
      examinations revealed leukocytosis and eosinophilia, and highly elevated levels
      of GOT, GPT, LDH and CPK. In the gastrocnemius muscle of a patient, roundly
      coiled nematode larvae were detected. The larvae measured 0.775-1.050 (av. 0.908)
      mm in length, and 0.026-0.042 (av. 0.035) mm in maximum width. The specific IgG
      antibody levels in three patients' sera were significantly higher when compared
      with those of normal controls. The patients were treated with flubendazole and
      albendazole for 15-30 days, and discharged at 13-34 days post-admission. From the
      above findings, it was confirmed that T. spiralis is present in Korea, and the
      badger plays a role of as the natural host.

PMID- 10905076
TI  - [Ureaplasma urealyticum vaginosis and premature rupture of membranes. What is its
      role?].
AB  - BACKGROUND: The aim of this study was to evaluate a correlation between PROM and
      genital infections. METHODS: A total of 308 vaginal swabs were made in randomized
      study group composed by 184 pregnant women aged between 26 and 32 years with an
      extreme age of 19 (one) and 40 years (one). Three vaginal swabs and one cervical
      swab (searching for Chlamydia) were made for every patient. Sixteen patients were
      excluded during this study, because they decided to have their babies in other
      hospitals. Therefore, the patients totally included in the study were 166: 109 at
      the first pregnancy, 33 at the second pregnancy and 5 at the third pregnancy. No
      one of them had any spontaneous abortion in the past. All possible other factor
      which ca be considered responsible and/or inductive of premature ruptures, such
      as cervical incontinence, cigarette smoke and coitus were excluded. RESULTS: 280
      vaginal swabs were made in this study: 134 were positive, with a global
      positivity percentage of 47.85%. Premature rupture of membranes (PROM) was
      observed in 38 cases with an incidence of 23.03%: 26 were PROM and 12 were pPROM.
      The extreme pPROMs occurred, respectively, at the 21st and at 34th gestational
      week; 29 of the 38 cases of PROM, were associated with positive cultures. The
      results obtained show an evident correlation between PROM and Ureaplasma
      urealyticum vaginosis: this fact is improved by the high incidence percentage of
      this mycobacter in pregnant women and also by an absolute predomination of
      Ureplasma urealyticum in PROM cases (72.41%). CONCLUSIONS: These data obtained
      confirm the importance of this microorganism in PROM genesis, according to some
      recent studies. It is suggested that Ureaplasma urealyticum infection can
      contribute to a premature start of labour.

PMID- 10905077
TI  - Vertical transmission of hepatitis C virus and follow-up of newborns from
      infected mothers.
AB  - BACKGROUND: Aim of the study is to analyze the rate of vertical transmission of
      HCV and the time of clearance of maternal antibodies in non-infected babies
      serum. METHODS: We have studied 36 babies born to HCV-positive and HIV-negative
      pregnant women at the University of Pavia. All mothers underwent blood tests to
      evaluate the presence of anti-HCV antibodies and viral RNA during pregnancy and
      after delivery. All babies underwent several tests at different times to evaluate
      the presence of viral RNA and the clearance of maternal antibodies. RESULTS: All
      babies proved HCV-Ab positive at birth, but only one case (2.7%) proved infected
      at PCR analysis. Different patterns of HCV-Ab clearance were noted in the 35 non
      infected babies. Of 24 babies from HCV-RNA-positive mothers, HCV-Ab reached zero
      in 24 months while in 11 babies from HCV-RNA-negative mothers, the antibodies
      disappeared at 12 months. A statistical difference was noted between the two
      groups of babies for the time of clearance of antibodies. CONCLUSIONS: The risk
      of vertical transmission in babies born to HCV-RNA negative mothers is very low,
      and the clearance of maternal antibodies is set within 12 months of follow-up.
      Mothers positive to HCV-RNA have a higher risk of transmitting the virus to their
      offspring and the time of clearance of antibodies in non-infected babies seems to
      be longer. A correct follow-up of these children must be no shorter than 24
      months.

PMID- 10905078
TI  - [Risk factors and neonatal outcomes in shoulder dystocia].
AB  - BACKGROUND: Shoulder dystocia (SD) is a rare obstetrical complication but linked
      with a high perinatal morbidity and mortality rate. SD has been associated to a
      series of maternal and fetal risk factors due to a multifactorial etiology. This
      study analyzes the incidence of SD, its morbidity and associated risk factors.
      METHODS: Cases of SD occurred at the St. Gerardo Hospital (Monza) between January
      1992 trough December 1997 have been retrospectively reviewed. Obstetrical and
      feto-neonatal data regarding cases of SD were compared to data regarding all the
      cephalic vaginal deliveries occurred in the same period in our Center. RESULTS: A
      total of 14,157 cephalic vaginal deliveries were included in this study, of these
      21 infants (0.15%) had SD. A significantly higher incidence of SD cases was found
      in fetal macrosomia, maternal diabetes, induction of labor by PGE2, use of
      obstetrical vacuum, length of first stage of labor > 4 hours in multiparas and >
      8 hours in nulliparas, and length of second stage > 60 minutes, regardless of
      parity. A closed association was also observed between SD and birth trauma as
      brachial plexus injury and humerus fracture. CONCLUSION: The incidence of SD in
      our population (0.15%) is below the average reported in the literature (0.37
      1.1%). The well-known risk factors, whose low positive predictive value can
      nevertheless modify obstetrical management, are confirmed.

PMID- 10905079
TI  - [Chronic pelvic pain in women and prevalent orthostatic work. Preliminary results
      of a study on health staff of the surgical field].
AB  - BACKGROUND: The purpose of this research is to estimate the causal and/or pre
      existing causal influence of some working factors, such as the standing
      (position) in pelvic pain syndrome, in relation to the reduction in working
      performance. METHODS: The research was carried out by means of an inclusive
      questionnaire, the purpose being to analyse anamnestic and working information.
      The questionnaire was proposed to a group of female sanitary staff selected in
      relation to their working activity. RESULTS: Examination of the questionnaire
      shows prominently the association between pelvic pain and orthostatic working
      activity, kept not below 4-6 hours each duty. In fact, 70% of the people selected
      have reported this mutual relationship. CONCLUSIONS: Working activities in the
      orthostatic position can produce pelvic pain, whose origin and intensity seem to
      be related to extended orthostatic working activity. The mechanism by which the
      upright position can produce an outbreak of pelvic pain in women seems to be
      linked to the compression on abdominal vessels, with slowing-down and reduction
      of the hematic uterine discharge.

PMID- 10905080
TI  - [Impact of neoangiogenesis on the survival of patients of patients with stage Ib
      IIb cervical carcinoma].
AB  - The survival of patients with cervical cancer has not improved much over the past
      few years. Cervical cancer is characterised by a degree of heterogeneity. Some
      patients undergoing surgery die a few months after diagnosis and treatment,
      whereas others live for longer and metastases only occur at a later stage. Over
      the past few years a new prognostic factor of cervical cancer has been
      identified. Neoangiogenesis can predict the possible metastasization of lymph
      nodes, disease-free survival, recidivation and therefore which patients require
      specific postoperative adjuvant therapies. This oncogenetic model, which also
      correlates the degree of neoangiogenesis with metastasization, and hence the
      level of tumour aggression, has been well demonstrated in lung cancer and skin
      melanoma. The microscopic discovery of increased tumour vascularization might be
      a useful independent prognostic factor in patients otherwise regarded as low
      risk. Cervical cancer with intense neoangiogenesis at an early phase may undergo
      rapid growth, early invasion and an increased capacity for metastasization.
      Neoangiogenesis is expressed as the density of microvessels inside the stroma of
      the neoplasm in invasive cervical cancer. It is predictive of recurrent disease
      and mortality independent of other prognostic factors. Patients with a high
      density of microvessels have a risk of fatal recidivation. The quantification of
      angiogenesis in primary tumours may be a useful prognostic factor in patients
      with cervical cancer. The quantification of neovascularization in neoplasms today
      is made easier by immunohistochemical staining procedures with greater
      specificity and sensitivity compared to conventional stains. It is to be hoped
      that this method will be used systematically by pathologists in biopsies to
      identify the most appropriate surgical and adjuvant therapies.

PMID- 10905081
TI  - [Microinvasive carcinoma of the uterine cervix. Risk factors and therapeutic
      options].
AB  - Aim of this study was to analyze the staging of disease according to correlation
      between depth of stromal invasion, lymph vascular space involvement, nodal
      metastases and recurrence and mortality rates in uterine cervical carcinoma. Data
      of 16 different surveys from 1980 to 1996 inclusive were collected through a
      Medline research; papers were selected according to available information about
      depth of invasion, lymph vascular invasion, nodal metastases, recurrence and
      mortality rate. Results of these surveys were pooled with the following aims: 1
      correlation between depth of invasion and nodal metastases occurrence; 2
      evolution of prognostic value of lymph vascular invasion; 3 best management
      according to biology of disease. Depth of stromal invasion seems to be the most
      important prognostic factor in early cervical cancer, with a critical cut-off of
      3 mm of depth. Lymph vascular invasion correlates both with nodal metastases and
      with prognosis, which strictly depends only on depth of invasion; as a
      consequence, lymph vascular invasion would not represent an independent
      prognostic factor. Finally radical treatment (i.e. more aggressive therapies)
      does not add any curative advantage when compared with conservative treatment,
      which must be currently considered standard in stage IA cervical cancer.

PMID- 10905082
TI  - [Neuroprotective effect of sodium channel blockers in ischemia: the  
      pathomechanism of early ischemic dysfunction].
AB  - Increase in the intracellular Na+ concentration ([Na+]i) plays a key role in the
      cell damage induced by ischemia/reperfusion. In addition to imposing an energy
      demand on cells due to stimulation of the plasmalemmal Na, K-ATPase, it
      contributes to an impairment of Ca2+ homeostasis by driving Ca2+ into the cells
      via the Na(+)-Ca2+ exchanger, and to the development of other acute dysfunctions
      such as acidosis, cytotoxic oedema and glutamate excitotoxicity. Rise is [Na+]i
      induced by ischemia further worsens during reperfusion when reactive oxygen
      species are generated, and oxidative stress occurs. As activation of voltage
      dependent Na+ channels has a crucial role in mediating a sustained Na+ entry
      during ischemia, blocking of these channels is expected to exert neuroprotection.
      Indeed, a wide range of compounds able to block Na+ channels proved to be
      beneficial in experimental ischemia. Among these are local anaesthetics, Ca2+
      channel blockers, anticonvulsants and the neuroprotective drug, vinpocetine.

PMID- 10905084
TI  - [The role of interval surgery and irradiation in the treatment of primarily non
      resectable rectal cancers].
AB  - The authors review the results of 1181 colorectal operations performed in a 16y
      period and analyze the last 8y period in which 713 colorectal operations were
      performed and the irradiation of primarily irresectable rectal cancer was
      introduced. At the time of the first operation 44% of the rectal cancer cases
      (69) proved to be irresectable, 14 of them were sent to a proper center as
      suitable ones for irradiation. 13 patients had got irradiation therapy [in three
      cases irradiation was combined with chemotherapy (5-fluorouracil)-
      synchronization chemoradiotherapy) and 11 of them were suitable for resection at
      the course of the second operation (there were performed 9 abdominoperineal
      resection and 2 Hartmann's procedures). In this small group (7% of rectal cancer
      cases) the radiotherapy can change the primarily irresecatable rectal cancer to
      resectable and for these patients this could be the only chance for cure.

PMID- 10905083
TI  - [Incidence and invasive treatment of congenital heart diseases in Hajdu-Bihar
      county].
AB  - The incidence of congenital heart diseases was evaluated in the period 1994-1998.
      The number of those who went through therapeutic intervention and those infants
      dying of congenital heart disease were also assessed. Data were collected
      retrospectively. During the study period 26,932 live-births occurred in Hajdu
      Bihar county and 421 congenital heart disease were diagnosed, 81% of whom were
      diagnosed under the age of one year. The most frequent diseases were secundum
      type atrial septal defect, ventricular septal defect and patent ductus
      arteriosus. 121 therapeutic procedures were performed (109 operations and 12
      interventional heart catheterizations). 41 interventions occurred under the age
      of one and 13 before the age of 28 days. The mean age of children older than 1
      year was 6 years at the time of the operation or interventional catheterization.
      The overall postoperative mortality within 30 days was 8.3%. During the study
      period 28 infants with significant heart disease died, 20 of whom also had an
      associated disease (most frequently prematurity). For congenital heart disease
      4.5 operations or interventional heart catheterizations were required/1000 live
      births. The higher rate of diagnosed congenital heart disease is due to the
      development in diagnostic techniques, especially to Doppler-echocardiography.
      Owing to the operational waiting list the children's age at the time of operation
      is higher than optimal. The mortality among infants with heart disease is
      influenced by many factors, that is why stepping forward is a complex task in
      this field.

PMID- 10905085
TI  - [Secondary cutaneous infiltration in B-cell chronic lymphocytic leukemia (B
      CLL)].
AB  - Authors report here on a case presenting as B-CLL and complicated with cutaneous
      infiltration involving the legs and the trunk a year later. Immunohistochemic
      analysis and the immunoglobulin heavy chain gene rearrangement confirmed cell
      invasion into the skin identical with the underlying disorder. After failure of
      conventional chemotherapy, interferon alpha 2b therapy has been started with
      satisfactory result. Few cases presenting cutaneous infiltration in the course of
      B-CLL has already been reported in the literature. Secondary cutaneous B-cell
      lymphoma represents an entity of the poorest prognosis in comparison with primary
      cutaneous form treated with conventional therapy as well as with lymphomas
      lacking skin manifestations. Interferon alpha 2b therapy cleans up the skin and
      yields a favourable survival so it's introduction recommended in this entity.
      Authors summarise the characteristics of secondary cutaneous B-cell lymphomas on
      the basis of literature survey. According to authors investigations histidine
      decarboxylase activity was found to be absent from the lymphocytes infiltrating
      the skin in contrast to those remaining in the circulation. This seems to be a
      newly recognised feature of these cells. The changing character of the disease
      raises the possibility of an altered gene expression pattern of the cells
      invading the skin. Authors summarise data from the literature concerning
      suspected molecular mechanism of tissue invasion.

PMID- 10905087
TI  - [Replacement of articular cartilage].

PMID- 10905088
TI  - [Did Chagas truly discover Chagas' disease?].

PMID- 10905086
TI  - [Occurrence of X-linked ichthyosis along with atopy].
AB  - The cases of children indicate suffering from X-linked ichthyosis accompanied by
      atopic diseases (bronchial asthma, allergic rhinitis, allergic conjunctivitis,
      atopic dermatitis) which developed in infancy. The examinations revealed
      microdeletion of the steroid sulfatase region (Xp22.3), increased total IgE value
      and polysensibilization. It seems that the steroid sulphatase deficiency in
      ichthyosis played a role in the development of the atopic diseases. The present
      study suggests the commencement of a strict diet and antihistamine therapy,
      already in its infancy, in order to prevent the development of the accompanying
      atopic diseases.

PMID- 10905089
TI  - [Hepatitis C virus].
AB  - Hepatitis C virus (HCV) is a small enveloped virus whose genome is a RNA molecule
      encoding a polyprotein that is processed by cellular and viral proteases to
      produce the 3 structural proteins (the core protein C and the 2 envelope proteins
      E1 and E2) and the 6 nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A and
      NS5B). The HCV genome exhibits a significant genetic heterogeneity. HCV isolates
      can be divided into genetically distinct groups referred to as genotypes, whereas
      the population of HCV genomes, within an infected individual, is present as a
      group of heterogeneous but closely related sequences referred to as quasi
      species. Studies of the molecular biology of HCV and of new vaccinal or
      therapeutic strategies are hampered by the lack of easy to use cellular culture
      systems and of animal models.

PMID- 10905090
TI  - [Epidemiology of hepatitis C].
AB  - The hepatitis C virus (HCV) has spread in a silent way by blood transfusion, then
      was massively introduced in the intravenous drug user community and is now
      recognized as a potential nosocomial viral infection. In France the prevalence of
      HCV seropositivity is around 1.1% with 500,000 to 650,000 persons affected, among
      whom 80% are chronic carriers of the virus. The proportion of HCV seropositive
      patients who knew their HCV serostatus increased from approximately 20% in 1994
      to around 50% in 1998. The prevalence of HCV infection varies by region (1.7% in
      Provence-Alpes-Cote d'Azur), increases with age, particularly after 50 years
      among women. The residual risk associated with transfusion is currently 2.7 per
      million blood donations, transmission among drug users remains high despite harm
      reduction measures and nosocomial transmission has been increasingly documented.
      In 1997, 1,800 deaths associated with hepatitis C occurred in France.

PMID- 10905091
TI  - [Diagnosis and biological surveillance of hepatitis C virus infections].
AB  - HCV-specific laboratory assays are broadly used to establish the diagnosis, to
      survey viral replication and to monitor anti-viral treatments. Third-generation
      ELISA's have an excellent sensitivity well adapted to the early diagnosis.
      Positive or dubious screening tests must be controlled on a second blood sample.
      We recommend the use of an immunoblot assay for this control. Regular survey of
      the immunoblot profile may facilitate the identification of recent infections and
      help distinguish between active or resolutive infections. PCR assays which detect
      HCV ARN in serum are very usefull to decide and monitor anti-viral treatments.
      Their cut-off is usually in the range of 100 genomes/mL. Quantitative assays to
      measure viral load may also rely on PCR technology or be based on the so-called
      "branched DNA" technology slightly less sensitive. Genotyping or serotyping of
      HCV is crucial to adapt specific treatment protocols to the less responsive
      genotypes 1a et 1b. Cloning and sequencing of HCV isolates is necessary to
      explore nosocomial clusters of infections or intra-familial cases.

PMID- 10905092
TI  - [Diagnosis and histologic surveillance of hepatitis C].
AB  - The role of liver biopsy in hepatitis C viral infection is diagnostic and
      prognostic. It states diagnoses of chronic hepatitis, cirrhosis and
      hepatocellular carcinoma. The association of portal lymphoid nodules,
      inflammatory bile duct lesions and steatosis suggests an hepatitis C viral
      etiology. Liver biopsy allows grading (extent of necro-inflammatory lesions) and
      staging (amount of fibrosis) of the disease using scoring systems proposed by
      Knodell et al. and (or) by METAVIR group. It can be helpful in confirming (or
      refuting) the presence of secondary diagnoses such as alcohol-induce liver
      disease or haemochromatosis and in assessing the efficacy of antiviral
      treatments.

PMID- 10905093
TI  - [Clinical forms and prognosis of hepatitis C].
AB  - Hepatitis C virus infects around 600,000 French people, mainly after parenteral
      exposure (in association with transfusion before 1990 and with intravenous drug
      use). Spontaneous resolution at the acute stage of the infection occurs in around
      30% of cases while chronic infection is observed in around 70% of cases and its
      main risk is evolution to cirrhosis. Three predictive factors of cirrhosis have
      been identified: the duration of infection (greater than 20 years), the age at
      contamination (greater than 40 years) and a chronic alcohol consumption (> 80
      g/day). Immunosuppressive situations (drug-related immune suppression for the
      prevention of graft rejection in allograft recipients or human immune deficiency
      virus-coinfection) as well as hepatitis B virus coinfection enhance the risk of
      cirrhosis and reduce the time of occurrence of cirrhosis. These predictors have
      to be considered in the information to the patients and in therapeutic decisions.
      They explain that any hepatitis C virus-infected patient has to undergo a liver
      biopsy to evaluate the necro-inflammatory activity and the fibrosis of the liver
      disease to delineate the place of a follow-up with a control of aggravation
      factors (alcohol discontinuation) and of an antiviral therapy.

PMID- 10905094
TI  - [Extrahepatic manifestations of hepatitis C virus infection].
AB  - HCV virus is associated with various immunological disorders. Some of them like
      mixed cryoglobulinemia, are proved by molecular biology and virology. Others are
      presumed auto-immune: auto-antibodies production (antinuclear, anti-smooth
      muscle, anti-liver-kidney microsomal antibodies...) has generally no pathological
      significance; however, true auto-immune diseases such as auto-immune hepatitis
      type 1 or 2, Sjogren's syndrome, lichen planus and auto-immune thyroiditis can be
      associated with HCV related liver disease. Finally, the association of some extra
      hepatic manifestations like porphyria cutanea tarda with hepatitis C virus are
      only based on epidemiological data. Alpha interferon, the reference treatment of
      chronic hepatitis C, can be efficient on manifestations such as cryoglobulinemia
      which are directly linked to the virus. However, because of its immunological
      effect, the same treatment can severely worsen auto-immunological diseases
      associated with hepatitis C virus (autoimmune hepatitis, thyroiditis...). In
      practice, it's of great importance to identify and classify these extra-hepatic
      manifestations to optimize the treatment of chronic hepatitis C.

PMID- 10905095
TI  - [Cirrhosis due to hepatitis C virus].
AB  - Occurrence of cirrhosis is a milestone in the protracted course of chronic
      hepatitis C. Indeed, liver decompensation and hepatocellular carcinoma occur only
      in cirrhotic patients, resulting in morbidity and mortality. Accordingly, being
      certain of cirrhosis diagnosis is needed. Clinical management of patients with
      compensated cirrhosis type C is mainly based on unspecific measures, such as
      stopping of regular drinking, preventive treatment of variceal haemorrhage,
      regular screening and early treatment of hepatocellular carcinoma. Interferon
      treatment is rarely effective from a virological point of view, but could result
      in a decreased incidence of clinical complications, particularly hepatocellular
      carcinoma. In patients with decompensated cirrhosis type C, liver transplantation
      is the only treatment allowing long-term survival.

PMID- 10905096
TI  - [Treatment and prevention of hepatitis C].
AB  - Hepatitis C is a chronic disease with lethal complications and recent treatments
      have a strong efficacy. Ribavirin and alpha interferon combination allows
      obtaining a sustained viral response in 40% of patients who are theoretically
      protected against the progression to cirrhosis and its complications. In non
      responders prospective trials are in progress assessing the efficacy of stronger
      regimen or using sustain-release interferons. It is also possible that in non
      responders interferon reduces the progression of liver fibrosis permitting to
      reduce cirrhosis incidence and to wait for new drugs. Patients who need
      definitively a treatment are patients with fibrosis progression, patients with
      extrahepatic manifestations and those who can transmit the virus. Treatment of
      HCV should be systematically discussed in patients coinfected with HIV and HCV.

PMID- 10905097
TI  - [Continuing medical education: a survey of the situation].

PMID- 10905098
TI  - [Non-traumatic spinal cord compression. Etiology, physiopathology, diagnosis].

PMID- 10905099
TI  - [Chronic glaucoma. Physiopathology, diagnosis, prognosis, principles of
      treatment].

PMID- 10905100
TI  - [Cutaneous and mucosal herpes. Epidemiology, physiopathology, diagnosis,
      prognosis, treatment].

PMID- 10905102
TI  - [Hemorrhage in the 3rd trimester of pregnancy. Diagnostic guidance].

PMID- 10905101
TI  - [Cancer cells. Genetic anomalies (oncogenes and anti-oncogenes), growth factors,
      apoptosis and dissemination, prognostic impact].

PMID- 10905103
TI  - [Pituitary adenoma in adults. Diagnosis, complications].

PMID- 10905104
TI  - [Evaluation of diagnostic or screening procedures. Validity of tests,
      sensitivity, specificity, predictive values. Definition and indications for mass
      screening].

PMID- 10905105
TI  - Distant ancestor of mankind unearthed: 520 million year-old fish-like fossils
      reveal early history of vertebrates.

PMID- 10905106
TI  - Drugs from nature? Synthesis of the isonitrin antibiotics.

PMID- 10905107
TI  - Evolution in the test tube as a means to create enantioselective enzymes for use
      in organic synthesis.
AB  - A novel method for the creation of mutant enzymes showing increased levels of
      enantioselectivity in a given synthetic organic reaction is reviewed. It makes
      use of directed evolution and is therefore independent of structural or
      mechanistic aspects. Accordingly, known molecular biological methods for random
      mutagenesis coupled with the proper expression system and high-throughput
      screening methods for enantioselectivity form the basis of this new approach. An
      example is the lipase-catalyzed hydrolytic kinetic resolution of a chiral ester
      in which the original enantioselectivity of 2% ee is increased to > 90% ee in
      just a few rounds of mutagenesis.

PMID- 10905108
TI  - Yeasts: providing questions and answers for modern biology.
AB  - Yeasts are to be found in virtually every conceivable niche on this planet and
      are amazingly varied in their shapes ('morphologies'), life cycles, metabolic
      capabilities, potentials for use in industrial processes, abilities to spoil food
      and drink or to act as dangerous human pathogens. This review describes four very
      different species of yeast to illustrate some of the diversity which exists and,
      in the case of one of them, Saccharomyces cerevisiae (the familiar baker's or
      brewer's yeast), the extent of both our knowledge and ignorance.

PMID- 10905109
TI  - Time-domain observation of conformational fluctuation of protein by time-resolved
      hole-burning spectroscopy.
AB  - Recent progress in structural biology has disclosed that protein function relies
      largely on its conformational flexibility. A protein molecule assumes a large
      number of slightly different conformations called "conformational substates
      (CSs)". At room temperature in an aqueous solution, transitions among many CSs
      take place and induce large conformational fluctuation, which is considered to be
      indispensable for its function. Time-resolved transient hole-burning (TRTHB)
      spectroscopy is becoming one of the most powerful tools to do direct time-domain
      measurement of the conformational fluctuation dynamics of a protein. In this
      technique, transition process among CSs is detected through the temporal
      variation of the "hole-burning" spectrum formed in the absorption spectrum by
      laser irradiation. Conformational fluctuation dynamics of protein is observed as
      a function of time in a very wide temporal range from ns up to ms. This article
      reviews some recent applications of TRTHB method to the observation of
      conformational fluctuation of myoglobin and cytochrome c.

PMID- 10905110
TI  - Analyzing liability insurance in Texas.

PMID- 10905111
TI  - MedBytes.

PMID- 10905112
TI  - Clean claims.

PMID- 10905113
TI  - Reaching common ground.

PMID- 10905114
TI  - A critical shortage.

PMID- 10905115
TI  - A class of their own.

PMID- 10905116
TI  - Delegating authority.

PMID- 10905118
TI  - Nitric oxide and cell respiration: physiology and pathology.
AB  - Two enzymes, the soluble guanylate cyclase and cytochrome c oxidase, have been
      shown to be exquisitely sensitive to nitric oxide (NO) at low physiological
      concentrations. Activation of the soluble guanylate cyclase by endogenous NO and
      the consequent increase in the second messenger cyclic GMP are now known to
      control a variety of biological functions. Cytochrome c oxidase (complex IV, the
      terminal enzyme of the mitochondrial respiratory chain) is inhibited by NO. We
      have shown that NO generated by vascular endothelial cells under basal and
      stimulated conditions modulates the respiration of these cells in response to
      acute changes in oxygen concentration. This action occurs at the level of complex
      IV and depends on influx of calcium. Thus, NO plays a physiological role in
      adjusting the capacity of this enzyme to use oxygen, allowing endothelial cells
      to adapt to acute changes in their environment. We have, in addition, studied the
      effect of long-term exposure to NO on different enzymes of the respiratory chain
      in a variety of cell lines. Our results show that, although NO inhibits complex
      IV in a way that is always reversible, prolonged exposure to NO results in a
      gradual and persistent inhibition of complex I that is concomitant with a
      reduction in the intracellular concentration of reduced glutathione. This
      inhibition appears to result from S-nitrosylation of critical thiols in the
      enzyme complex because it can be immediately reversed by exposing the cells to
      high intensity light or by replenishment of intracellular reduced glutathione.
      Furthermore, decreasing the concentration of reduced glutathione accelerates the
      process of persistent inhibition. Our results suggest that, although NO may
      regulate cell respiration physiologically by its action on complex IV, long-term
      exposure to NO leads to persistent inhibition of complex I and potentially to
      cell pathology.

PMID- 10905117
TI  - Community intervention to screen risk of cardiovascular diseases in a rural Texas
      community.
AB  - This study describes the effectiveness of cardiovascular risk screening for
      elderly patients of a primary care practice in a rural community. A controlled
      trial sample of 44 eligible patients was screened in a primary care practice
      setting in August 1998. All patients completed health risk questionnaires; 93% of
      the 44 had laboratory work and a complete physical examination. Cost comparisons
      were made between the cost of the health screening and the cost of
      hospitalization for cardiovascular disease in Fort Worth, Tex. Within the sample
      population, the mean age was 67.9 years (+/- 8.1). A high prevalence of obesity
      among females (53%), hypertension (58.5%), lipid disorders (63.4%), and elevated
      glucose levels (19.5%) was found. Preventive health screenings and programs can
      be cost-effective in identifying and managing major disease (cardiovascular
      diseases, lipid disorders, and diabetes) and in preventing potential costly
      hospitalizations.

PMID- 10905119
TI  - The physiology and the pathophysiology of the gastric accommodation reflex in
      man.
AB  - Summarizing the previous sections, we have demonstrated that the gastric
      accommodation reflex in man involves the release of serotonin and the activation
      of a nitrergic motor neuron. We observed that almost half of the patients with
      functional dyspepsia have an impaired accommodation reflex, and this is
      associated with early satiety and weight loss. Drug-induced inhibition of the
      accommodation reflex is able to induce early satiety in healthy subjects.
      Administration of the anti-migraine drug sumatriptan, an agonist at 5-HT1P
      receptors on gastric myenteric neurons, causes a relaxation of the proximal
      stomach in man through a nitrergic pathway. Pretreatment with sumatriptan is able
      to restore impaired accommodation and to improve early satiety in patients with
      functional dyspepsia. We conclude from these data that fundus-relaxing drugs may
      have a therapeutic potential in functional dyspepsia, and we hypothesize that
      fundus-contracting drugs may have therapeutic potential in the treatment of
      obesity.

PMID- 10905120
TI  - The bovine cytotoxic T cell: MHC restriction and antigen-specificity.
AB  - The analysis of the immune mechanisms operative against the bovine intracellular
      protozoan parasite Theileria parva resulted in the identification and
      characterisation of the bovine cytotoxic T lymphocyte (CTL) and its important
      role in protection against this parasite. By the use of polyclonal and monoclonal
      antibodies specific for bovine MHC antigens and lymphocyte populations and the
      use of MHC-haplotyped animals it was possible to demonstrate the MHC restriction
      and antigen-specificity of the Theileria-specific cytotoxicity. In cross
      protection studies with different parasite stocks or strains, a consistent
      correlation could be observed between the strain specificity of the CTL and the
      in vivo cross-protection. Moreover, the in vitro generation of CTL lines and
      clones and the development of a standardised technique for analysing the
      frequency of parasite-specific CTL precursors in cattle immunised with Theileria
      parva, enabled the identification of parameters influencing the parasite strain
      specificity of the cytotoxic response. Not only the immunising parasite but also
      the bovine MHC haplotype of the respective immunised animal influenced whether
      the Theileria-specific CTL were strain-specific or cross-reactive between
      strains. These results have important implications for the identification of
      cross-reactive CTL epitopes of the parasite in the development of subunit
      vaccines for outbred animals.

PMID- 10905121
TI  - Long-term results after bronchial sleeve resection.
AB  - In bronchial sleeve resections part of the bronchial wall is removed followed by
      the creation of a bronchial end-to-end anastomosis. The cylindrical part that is
      removed is called a "sleeve". In this way functional lung parenchyma can be saved
      in centrally located bronchogenic carcinomas while performing an oncologically
      valid operation. However, controversial results were reported in literature
      regarding long-term survival after bronchial sleeve resection especially in
      relation to nodal status. In a series of 145 patients undergoing bronchial sleeve
      resection for a bronchogenic tumor in the Antonius Hospital, Nieuwegein, the
      Netherlands, long-term results were studied. A univariate and multivariate
      analysis were performed to determine significant factors related to survival.
      Follow-up was updated until 1999, so a minimum follow-up of 10 years was obtained
      for surviving patients. For the entire group 5, 10 and 15-year survival rates
      were 45, 35 and 23%, respectively. Median survival time was 52 +/- 10 months.
      Five- and 10-year survival rates for the 71 patients with N0 disease were 62% and
      53%, respectively; for the 58 patients with N1 disease, 29% and 21%; and for the
      16 patients with N2 disease, 31% and 6%. There was a highly significant
      difference in survival between patients with N0 and N1 (p = 0.001) or N2 (p <
      0.001) disease. The difference between N1 and N2 disease reached statistical
      significance (p = 0.047). A Cox multivariate regression analysis showed only
      nodal stage and patient age to be significant factors in relation to survival. To
      improve long-term survival adjuvant treatment should be considered in case of N1
      or N2 disease as most of these patients die of distant metastases.

PMID- 10905122
TI  - [The coronary circulation and myocardial ischemia].
AB  - In this review concerning the relationship between coronary circulation and
      myocardial ischemia, the authors focus on the factors influencing myocardial
      oxygen demand and supply, through the evaluation of the determinants of
      myocardial oxygen consumption and coronary flow regulation. The concepts of
      coronary flow reserve and endothelial control, the latter being probably a link
      among vasoconstriction, thrombosis and inflammation in the genesis of acute
      ischemic syndromes, have been particularly investigated. Moreover, the
      hemodynamic effects of coronary artery stenoses have been shortly mentioned. The
      complex mechanisms involved in the regulation of coronary artery tone and flow
      and the evolution of atherosclerotic plaques are clinically expressed in the so
      called "ischemic cascade" leading from local ischemia to chest pain.

PMID- 10905123
TI  - [Hypertension and the coronary circulation].
AB  - The main alteration of coronary circulation in systemic hypertension is mostly
      dependent on the reduction of the coronary vasodilating reserve, due to various
      mechanisms: left ventricular hypertrophy, functional and structural alterations
      of the coronary microcirculation, anatomic modifications, and atherosclerosis of
      epicardial vessels. The role of endothelial dysfunction is important as well.
      Diagnosis of myocardial ischemia is, therefore, difficult in these subjects. The
      use of exercise ECG is limited by a high false positive incidence in diagnosing
      coronary stenosis, whereas exercise stress echocardiography, far more specific,
      may be considered the diagnostic tool of choice.

PMID- 10905124
TI  - [Ischemic cardiopathy: risk factors and their biological role].
AB  - Atherosclerosis is a slowly progressive process, involving the intima and media
      of large and medium sized arteries and leading to the formation of focal lesions
      (plaques), containing lipid and fibrous tissue. A classification of
      atherosclerotic lesions includes: isolated foam cells, fatty streaks,
      preatheroma, atheroma, and fibroatheroma. Fibroatheroma is an unstable lesion,
      which might be complicated by intraplaque hemorrhage, rupture and overimposed
      thrombosis, leading to ischemia. This is the main mechanism responsible for
      myocardial infarction, stroke, and intermittent claudication. A widely accepted
      hypothesis for the pathogenesis of atherosclerosis is the response to the injury
      hypothesis. Endothelial damage or dysfunction is associated with increased
      arterial wall permeability to plasma constituents and with adhesion of platelets
      and monocytes, releasing growth factors and chemoattractant molecules. Several
      factors, in particular hyperlipidemia, arterial hypertension, diabetes mellitus,
      produce endothelial damage, which is followed by other cellular reactions
      involved in the atherosclerotic process. Since long time it has been reported
      that atherosclerosis has some features of the inflammatory processes. The
      inflammatory response in the arterial system is to some extent different from
      that occurring in other tissues and organs, such as the liver, kidney, lung or
      joints. The measurement of metabolic markers of coronary risk (cholesterolemia,
      homocysteinemia, glycosylated hemoglobin) is useful to estimate the global
      coronary risk in the individual patient. The demonstration of atherosclerotic
      plaques by noninvasive ultrasounds provides a sensitive marker of early arterial
      disease, allowing an objective evaluation of the response of the arterial system
      to different treatments.

PMID- 10905125
TI  - [Hypertension as a function of age].
AB  - Hypertension is one of the main risk factors for cerebrovascular disease
      (stroke), coronary artery disease (acute myocardial infarction), congestive heart
      failure (both systolic and diastolic dysfunction), and renal dysfunction. The
      risk is related to blood pressure level and to the presence of target organ
      damage. Together with hypertension, other cardiovascular risk factors, such as
      hyperlipidemia and/or diabetes, also contribute to the chain of events leading to
      atherosclerosis, vascular complications and death. Three-quarters of middle-aged,
      urban population show at least one cardiovascular risk factor and 91.3% of all
      hypertensives show at least one cardiovascular risk factor in addition to
      hypertension itself. In most populations, the risk of cardiovascular disease
      rises steeply with age. This powerful effect of age on disease risk has important
      consequences for the risk of cardiovascular disease related to blood pressure and
      other risk factors. At most ages the risk for cardiovascular diseases is higher
      in men than in women, although this difference declines with increasing age and
      is greater for coronary heart disease than for stroke; in the United States from
      age 34 to 74 the risk of death from coronary heart disease is 2- to 3-fold
      greater in men; the risk of death from stroke is 30% higher in men than in women;
      after age 75 the risk of death from stroke and from coronary heart disease is
      similar in men and women. Postmenopausal women share the same risk with men for
      cardiovascular disease. For many years the study and treatment of hypertension
      has been largely directed toward diastolic blood pressure; the importance of
      elevated systolic blood pressure in the management of cardiovascular disease is
      being largely underrecognized. Convincing evidence is presently available
      indicating that elevated systolic blood pressure is even a stronger predictor
      than diastolic blood pressure for progression of cardiovascular disease and
      adverse outcomes. The clinical and laboratory evaluation and drug treatment of
      the hypertension is related to age. The elderly benefit from treatment of
      elevated systolic blood pressure as much or even more than middle-aged
      hypertensive subjects. Two large clinical trials on treatment of isolated
      systolic hypertension, the Systolic Hypertension in the Elderly Program (SHEP)
      and the Systolic Hypertension in Europe Study (Syst-Eur), have demonstrated that
      antihypertensive drug therapy in elderly patients with isolated systolic
      hypertension effectively reduces the risk of stroke and other major
      cardiovascular events.

PMID- 10905126
TI  - [Changes in the cardiac rhythm in ischemic cardiopathy].
AB  - Ventricular arrhythmia associated with ischemic heart disease has an important
      role in the etiology of sudden death, both in acute and chronic coronary
      syndromes. The etiopathogenesis of ventricular arrhythmia is strictly linked to
      the time-course from the occurrence of coronary occlusion. In the very acute
      phase of the ischemia, ventricular arrhythmias are due to a reentry mechanism,
      while 4-8 hours after occlusion the enhanced automatism, and triggered activity
      are the key mechanisms. Therefore reentry mechanisms are the main factors
      responsible for postinfarction arrhythmias. Also autonomic mechanisms,
      electrolytes and pharmacological therapy may contribute to cause arrhythmias.

PMID- 10905127
TI  - [Cardiac rhythm disturbances in hypertensive cardiopathy].
AB  - Patients with hypertensive heart disease are at a significantly increased risk
      for cardiovascular morbidity and mortality. Ultrastructural and gross anatomical
      cardiac changes, combined with hemodynamic and neurovegetative balance
      fluctuations, are frequently responsible for cardiac arrhythmias of atrial and/or
      ventricular origin. The prevalence, the pathophysiologic mechanism and the
      prognostic significance of cardiac rhythm disturbances occurring in hypertensive
      heart disease are discussed in this review.

PMID- 10905128
TI  - [Physiological and pathological cardiac hypertrophy].
AB  - The clinical, electrocardiographic or echocardiographic documentation of cardiac
      hypertrophy in hypertensive patients implies relevant interpretations concerning
      both the prognosis and a more precise definition of its etiology. Moreover, the
      finding of myocardial ischemia in these patients requires a precise diagnostic
      protocol directed to define whether the reduction of coronary reserve is
      justified by hypertension or is due to an associated coronary artery disease.

PMID- 10905129
TI  - [The primary and secondary prevention of ischemic cardiopathy].
AB  - The aim of this paper was to summarize the most important clinical issues on
      coronary artery disease prevention, in order to provide the best advice to
      cardiologists, and facilitate their work on primary and secondary prevention.
      Although in recent years the knowledge of the beneficial effects of major risk
      factor modification has been increasing, most physicians still concentrate only
      on patients with overt coronary artery disease. Many high-risk individuals are
      not adequately advised and treated, whilst a great effort should be made by
      national institutions and individual doctors to implement primary prevention
      schemes. Indeed, the potential for preventive measures is greatest in high-risk
      groups. Specific international task forces have issued official recommendations
      on the prevention of coronary heart disease in clinical practice, which have been
      intended to encourage the development and revision of national guidelines on
      coronary prevention. The challenge for cardiologists in the year 2000 is to
      realize the potential for coronary prevention in all patients, and to contribute
      to reduce the enormous socio-economic burden of cardiovascular disease.

PMID- 10905130
TI  - [The primary and secondary prevention of hypertensive cardiopathy].
AB  - Antihypertensive treatment is useful in reducing cardiovascular morbidity and
      mortality. The possibility of preventing cardiac events is mainly related to the
      effect of antihypertensive drugs on the occurrence of hypertensive heart disease,
      i.e. on the anatomic and functional abnormalities of the left ventricle that
      represent the direct consequence of blood pressure increase. Hypertensive heart
      disease is associated with the concomitant occurrence of structural and
      functional changes in large arteries and small resistance arteries. Left
      ventricular hypertrophy represents the sign of preclinical disease in
      hypertensive heart disease. The use of antihypertensive treatment may induce the
      regression of left ventricular hypertrophy and determine a significant
      improvement of functional and clinical consequences of cardiac hypertrophy, and
      more importantly the regression of left ventricular hypertrophy is associated
      with an improvement of cardiovascular prognosis in hypertensive patients. It
      remains to be established whether some antihypertensive drugs are more effective,
      or only faster, in determining left ventricular hypertrophy regression.
      Antihypertensive treatment is extremely useful not only in the primary prevention
      of cardiac events and hypertrophy, but also in the reduction of cardiac
      complications in patients already presenting with cardiac disease; in fact these
      patients are at higher cardiovascular risk and therefore the benefit from blood
      pressure reduction may be even more evident.

PMID- 10905131
TI  - [Cardiac failure in ischemic cardiopathy].
AB  - Heart failure is a major cause of morbidity and mortality and represents an
      important recognized health problem. Heart (or cardiac) failure is the
      pathophysiological state in which a myocardial dysfunction is frequently but non
      always responsible for the inability of the heart to pump blood at a rate
      commensurate with tissues metabolic requirements. Ischemic heart disease is the
      commonest cause of heart failure frequently associated with left ventricular
      systolic dysfunction, although some patients, particularly the elderly, have
      diastolic dysfunction. Coronary heart disease is responsible for left ventricular
      systolic dysfunction (and cardiac failure) in the acute and chronic stage.
      Myocardial dysfunction is usually a consequence of myocardial infarction that may
      lead to ventricular remodeling with compensatory dilation and hypertrophy and
      subsequent systolic and diastolic dysfunction resulting in heart failure. Many
      patients with heart failure and/or left ventricular dysfunction are unknown. The
      echocardiographic screening of patients with known or suspected left ventricular
      dysfunction remains an important topic for future clinical epidemiological
      research and allows for improvement of therapeutic management of patients with
      cardiac dysfunction.

PMID- 10905132
TI  - [Cardiac failure in hypertensive cardiopathy].
AB  - Elevated blood pressure and left ventricular hypertrophy are powerful independent
      predictors of heart failure. In hypertension, left ventricular hypertrophy at
      electrocardiography doubles the risk of heart failure. The individual absolute
      risk of heart failure, however, remains quite low in the absence of myocardial
      infarction, valvular heart disease and diabetes. For example, in a 60-year-old
      asymptomatic man with systolic blood pressure 160 mmHg, the risk of developing
      heart failure is 0.37% per year in the absence of left ventricular hypertrophy
      and 0.90% per year in the presence of hypertrophy. If ischemic heart disease,
      valvular heart disease and diabetes coexist in the same subject, the risk of
      heart failure rises to 5.1% and 9.5% in the absence and presence of left
      ventricular hypertrophy, respectively. Several mechanisms may explain the
      increased risk of heart failure in hypertensive subjects with left ventricular
      hypertrophy. Among these, increased collagen deposition in the interstitial space
      among myocytes could lead to impaired diffusion of oxygen and other substances
      towards hypertrophied myocytes, whose metabolic demand is increased. Left
      ventricular hypertrophy increases the risk of heart failure both at normal
      (diastolic) and low cardiac output. There is an inverse association between left
      ventricular mass and velocity of diastolic relaxation. Early diagnosis of left
      ventricular hypertrophy through electrocardiography or echocardiography and
      aggressive treatment of patients with hypertrophy are probably the best ways to
      prevent heart failure associated with hypertension. Controlled intervention
      studies clearly showed that treatment of hypertension reduces the occurrence of
      heart failure by 25-50%, particularly in the elderly with isolated systolic
      hypertension. In a sizable proportion (about 20%) of asymptomatic patients with
      hypertension, left ventricular systolic performance estimated by echocardiography
      at mid-wall level is reduced. These patients appear to be at increased risk of
      major cardiovascular events including heart failure.

PMID- 10905133
TI  - [Interventional or conservative approaches in acute coronary syndromes].
AB  - The past decade has witnessed a dramatic expansion in the scope of both
      mechanical and pharmacologic methods for treating patients with acute coronary
      syndromes. New device technologies, such as intracoronary stenting, more potent
      and more fibrin-specific thrombolytic agents, and new antithrombotic and
      antiplatelet drugs are now available. What is the best strategy to treat patients
      with acute coronary syndromes still remains a matter of debate. This article
      briefly reviews this topic.

PMID- 10905134
TI  - [From the great clinical studies to the management of the single patient. Medical
      therapy in the pre- and post-fibrinolytic era].
AB  - Medical therapy of myocardial infarction has changed over the last 30 years. The
      "lag phenomenon", i.e. the time lapsing from the appraisal of a new, relevant
      scientific evidence and its practical adoption, has been variable, and different
      from one treatment to another. It has been very short for GP IIb/IIIa receptor
      inhibitors in candidates for urgent coronary angioplasty after myocardial
      infarction, short for ACE inhibitors, and it has been also short for the decrease
      in the prescription of calcium channel inhibitors after controversial scientific
      evidence. This time lapse has been long for beta-blockers, that only now are used
      quite extensively in Italy: from less than 10% of hospitalized patients during
      the early '80s, to over 60% nowadays. This evolution of medical therapy has been
      progressive and continuous, has not been divided into two eras, and thrombolysis
      seems to have little to do with it. The extensive introduction of thrombolysis
      has simply divided patients with acute myocardial infarction into two subgroups,
      very different for clinical characteristics: candidates for this therapy, and
      "others". Candidates for thrombolysis have a much better prognosis, but for a
      "paradox effect" they have been studied much more than the others. Now, the bulk
      of publications concerning patients undergoing thrombolysis carries the risk of
      spreading the concept that myocardial infarction has changed. We do not think
      that this corresponds to reality. Probably, the concepts that have guided medical
      therapy have been very similar and unchanged over the years, and both medical and
      surgical plus coronary angioplasty therapies are today much more appropriately
      used than yesterday.

PMID- 10905135
TI  - [Systolic-diastolic arterial hypertension versus isolated systolic hypertension].
AB  - The presence of elevated values of both diastolic and systolic arterial blood
      pressure is one of the most important risk factors for coronary heart disease,
      stroke, and heart failure; in patients with hypertension, the pharmacological
      reduction of blood pressure decreases the risk of adverse cardiovascular events,
      though the optimal blood pressure goal is still being debated. During recent
      years there has been an increasing interest in isolated systolic hypertension,
      both as an independent risk factor for cardiovascular disease and as a clinical
      entity requiring treatment in its own right. The definition of what constitutes
      isolated systolic hypertension still remains controversial and arbitrary; the
      criteria generally used is a systolic blood pressure > or = 140 mmHg and a
      diastolic blood pressure < 90 mmHg. Not only the cut-off levels used to define
      isolated systolic hypertension, but also the number of occasions on which blood
      pressure is measured can significantly affect the prevalence of isolated systolic
      hypertension in the total population. The use of 24-hour ambulatory blood
      pressure monitoring is a relatively new method for overcoming transient
      elevations in blood pressure that often occur during clinic measurement; it has a
      good reproducibility, is subject to little "white-coat" or placebo effect, and
      finally provides blood pressure measurements within a subject's normal
      environment. Borderline isolated systolic hypertension (defined as a systolic
      blood pressure between 140 and 159 mmHg and a diastolic blood pressure < 90 mmHg)
      is probably the most common type of untreated hypertension among adults over the
      age of 60; in the following 20 years, about 80% of patients with borderline
      isolated systolic hypertension will show progression to definite hypertension
      with increased risk of development of cardiovascular disease. The increase in
      systolic and diastolic blood pressure with age is typical of Western societies,
      while it is not observed among some "unacculturated" populations, who tend to be
      lean and physically active, with a lower daily sodium intake. Maybe
      environmental, rather than genetic factors may contribute more to the
      determination of blood pressure throughout life. Pharmacological treatment of
      isolated systolic hypertension can lead to a significant reduction in total
      stroke, coronary heart disease, and cardiovascular disease. The question of which
      antihypertensive agents are most effective is still to be fully elucidated with
      specifically addressed trials.

PMID- 10905136
TI  - [Hypertension and the progression of organ damage].
AB  - The heart is one of the most important targets of arterial hypertension to which
      this organ responds with the development of left ventricular hypertrophy. This
      structural alteration, which is rather frequent already in the early stages of
      hypertension, derives from a complex interaction of hemodynamic and humoral
      factors and represents a compensatory mechanism for maintaining a normal cardiac
      output in spite of the elevated peripheral resistance; yet, with time, left
      ventricular hypertrophy exposes patients to an additive risk of ischemia,
      dysrhythmias and cardiac failure. However the progression towards these clinical
      manifestations of cardiac deterioration is susceptible nowadays to be halted
      thanks to the efficacy of antihypertensive drugs and particularly of those
      antagonizing the activity of the renin-angiotensin system.

PMID- 10905234
TI  - A case of market failure.

PMID- 10905235
TI  - Short-acting inhaled beta-agonists: to be taken regularly or as needed?

PMID- 10905236
TI  - Haemangioblast origin of chronic myeloid leukaemia?

PMID- 10905237
TI  - Improving accuracy of cytology for nodular thyroid lesions.

PMID- 10905238
TI  - Safe feeding methods in stroke patients.

PMID- 10905239
TI  - Programmatic goals and approaches to onchocerciasis.

PMID- 10905240
TI  - Effect of population screening and treatment for Helicobacter pylori on dyspepsia
      and quality of life in the community: a randomised controlled trial. Leeds HELP
      Study Group.
AB  - BACKGROUND: Infection with Helicobacter pylori is the main cause of peptic-ulcer
      disease. Treatment of this infection might lower the prevalence of dyspepsia in
      the community and improve quality of life. We investigated this possibility in a
      double-blind randomised controlled trial. METHODS: Individuals aged 40-49 years
      were randomly selected from the lists of 36 primary-care centres. A researcher
      interviewed participants with a validated dyspepsia questionnaire and the
      psychological general wellbeing index (PGWB). H. pylori status was assessed by
      the carbon-13-labelled urea breath test. Infected participants were randomly
      assigned active treatment (omeprazole 20 mg, clarithromycin 250 mg, and
      tinidazole 500 mg, each twice daily for 7 days) or identical placebo.
      Participants were followed up at 6 months and 2 years. FINDINGS: Of 32,929
      individuals invited, 8455 attended and were eligible; 2324 were positive for H.
      pylori and were assigned active treatment (1161) or placebo (1163). 1773 (76%)
      returned at 2 years. Dyspepsia or symptoms of gastro-oesophageal reflux were
      reported in 247 (28%) of 880 in the treatment group and 291 (33%) of 871 in the
      placebo group (absolute-risk reduction 5% [95% CI 1-10]). H. pylori treatment had
      no significant effect on quality of life (mean difference in PGWB score between
      groups 0.86 [-0.33 to 2.05]). INTERPRETATION: Community screening and treatment
      for H. pylori produced only a 5% reduction in dyspepsia. This small benefit had
      no impact on quality of life.

PMID- 10905241
TI  - Validity and reliability of a quantitative computed tomography score in
      predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS
      Study Group. Alberta Stroke Programme Early CT Score.
AB  - BACKGROUND: Computed tomography (CT) must be done before thrombolytic treatment
      of hyperacute ischaemic stroke, but the significance of early ischaemic change on
      CT is unclear. We tested a quantitative CT score, the Alberta Stroke Programme
      Early CT Score (ASPECTS). METHODS: 203 consecutive patients with ischaemic stroke
      were treated with intravenous alteplase within 3 h of symptom onset in two North
      American teaching hospitals. All pretreatment CT scans were prospectively scored.
      The score divides the middle-cerebral-artery territory into ten regions of
      interest. Primary outcomes were symptomatic intracerebral haemorrhage and 3-month
      functional outcome. The sensitivity and specificity of ASPECTS for the primary
      outcomes were calculated. Logistic regression was used to test the association
      between the score on ASPECTS and the primary outcomes. FINDINGS: Ischaemic
      changes on the baseline CT were seen in 117 (75%) of 156 treated patients with
      anterior-circulation ischaemia included in the analysis (23 had ischaemia in the
      posterior circulation and 24 were treated outside the protocol). Baseline ASPECTS
      value correlated inversely with the severity of stroke on the National Institutes
      of Health Stroke Scale (r=-0.56, p<0.001). Baseline ASPECTS value predicted
      functional outcome and symptomatic intracerebral haemorrhage (p<0.001, p=0.012,
      respectively). The sensitivity of ASPECTS for functional outcome was 0.78 and
      specificity 0.96; the values for symptomatic intracerebral haemorrhage were 0.90
      and 0.62. Agreement between observers for ASPECTS, with knowledge of the affected
      hemisphere, was good (kappa statistic 0.71-0.89). INTERPRETATION: This CT score
      is simple and reliable and identifies stroke patients unlikely to make an
      independent recovery despite thrombolytic treatment.

PMID- 10905242
TI  - Regular inhaled salbutamol and asthma control: the TRUST randomised trial.
      Therapy Working Group of the National Asthma Task Force and the MRC General
      Practice Research Framework.
AB  - BACKGROUND: Previous work has suggested that the long-term regular use of inhaled
      beta2-agonist bronchodilators might lead to a deterioration in asthma control.
      The aim of TRUST (The Regular Use of Salbutamol Trial) was to study the effects
      of regular use of inhaled salbutamol, the most widely prescribed bronchodilator
      in the UK, on the control of asthma. METHODS: A randomised, double-blind, placebo
      controlled trial was undertaken in 983 patients with asthma being treated at
      least twice a week with short-acting beta2-agonist, alone or in combination with
      inhaled steroids (2 mg or less) daily. Patients were aged 18 years and over and
      were recruited from 115 general practices in the UK. 90% (881) of the patients
      used inhaled corticosteroid therapy, and all patients continued to use their
      usual inhaled beta2-agonist for symptomatic relief. Patients were randomised to
      receive 400 microg salbutamol or matched placebo via a Diskhaler four times per
      day for 12 months. The primary outcome measure was rate of exacerbations of
      asthma, with criteria based on data from diary cards completed daily by each
      patient, treatment with additional corticosteroids, or both. FINDINGS: There were
      no differences in the annual rate, timing, or duration of exacerbations between
      the two groups. The mean morning peak expiratory flow was similar for the two
      groups. The mean evening peak expiratory flow (p<0.001) and the diurnal variation
      (p<0.001) were greater, and the use of rescue bronchodilator was less (p<0.001),
      in the group receiving regular salbutamol. INTERPRETATION: There was no evidence
      that regular use of inhaled salbutamol 400 microg four times daily for a year
      increased the exacerbation rate of asthma in the population studied.

PMID- 10905243
TI  - Relation between house-dust endotoxin exposure, type 1 T-cell development, and
      allergen sensitisation in infants at high risk of asthma.
AB  - BACKGROUND: Bacterial endotoxin is known to induce interferon gamma and
      interleukin 12 production, and therefore has the potential to decrease allergen
      sensitisation. To find out the role of early chronic endotoxin exposure in the
      development of allergen sensitisation and asthma, we compared concentrations of
      endotoxin in house dust with allergen sensitisation in infants at high risk for
      developing asthma. METHODS: 61 infants 9-24 months old with at least three
      physician-documented episodes of wheezing were studied. Concentrations of house
      dust endotoxin and allergens were measured in the infants' homes. Allergen
      sensitisation was measured by skin-prick testing with a panel of common inhalant
      and food allergens. In a subset of these infants, proportions of T lymphocytes
      producing interferon gamma, and interleukins 4, 5, and 13 were calculated by cell
      surface and intracellular cytokine staining, with flow cytometry. FINDINGS: House
      dust endotoxin concentrations ranged from 104 to 10,000 endotoxin units (EU) per
      mL (geometric mean 912 EU/mL). Concentrations did not vary significantly over a 6
      month interval. Ten infants (16%) were sensitised to at least one allergen. The
      homes of allergen-sensitised infants contained significantly lower concentrations
      of house-dust endotoxin than those of non-sensitised infants (mean 468 vs 1035
      EU/mL, respectively; p=0.01). Increased house-dust endotoxin concentrations
      correlated with increased proportions of interferon-gamma-producing CD4 T cells
      (p=0.01). Such concentrations did not correlate with proportions of cells that
      produced interleukins 4, 5, or 13. INTERPRETATION: This study may provide the
      first direct in-vivo evidence that indoor endotoxin exposure early in life may
      protect against allergen sensitisation by enhancing type 1 immunity.

PMID- 10905244
TI  - Stroke mortality in urban and rural Tanzania. Adult Morbidity and Mortality
      Project.
AB  - BACKGROUND: Most data for stroke mortality in sub-Saharan Africa are hospital
      based. We aimed to establish the contribution of cerebrovascular disease to all
      cause mortality and cerebrovascular disease mortality rates in adults aged 15
      years or more in one urban and two rural areas of Tanzania. METHODS: Regular
      censuses of the three surveillance populations consisting of 307,820 people
      (125,932 aged below 15 years and 181,888 aged 15 or more) were undertaken with
      prospective monitoring of all deaths arising in these populations between June 1,
      1992 and May 31, 1995. Verbal autopsies were completed with relatives or carers
      of the deceased to assess, when possible, the cause of death. FINDINGS: During
      the 3-year observation period 11,975 deaths were recorded in the three
      surveillance areas, of which 7629 (64%) were in adults aged 15 years or more
      (4088 [54%] of these in men and 3541 [46%] in women). In the adults, 421 (5.5%)
      of the deaths were attributed to cerebrovascular disease, 225 (53%) of these in
      men and 196 (47%) in women. The yearly age-adjusted rates per 100,000 in the 15
      64 year age group for the three project areas (urban, fairly prosperous rural,
      and poor rural, respectively) were 65 (95% CI 39-90), 44 (31-56), and 35 (22-48)
      for men, and 88 (48-128), 33 (22-43), and 27 (16-38) for women, as compared with
      the England and Wales (1993) rates of 10.8 (10.0-11.6) for men and 8.6 (7.9-9.3)
      for women. INTERPRETATION: We postulate that the high rates in Tanzania were due
      to untreated hypertension. Our study assessed mortality over a single time period
      and therefore it is not possible to comment on trends with time. However, ageing
      of the population is likely to lead to a very large increase in mortality from
      stroke in the future.

PMID- 10905246
TI  - Worrisome striae in pregnancy.

PMID- 10905245
TI  - Evidence from a leukaemia model for maintenance of vascular endothelium by bone
      marrow-derived endothelial cells.
AB  - BACKGROUND: Vascular endothelial cells lost from the blood-vessel endothelium
      through necrosis or apoptosis must be replaced. We investigated in a leukaemia
      model whether bone-marrow-derived endothelial cells contribute to this
      maintenance angiogenesis. METHODS: We studied six patients with chronic
      myelogenous leukaemia (CML) carrying the BCR/ABL fusion gene in their bone-marrow
      derived cells. We screened endothelial cells generated in vitro from bone-marrow
      derived progenitor cells and vascular endothelium in myocardial tissue for the
      BCR/ABL fusion gene by in-situ hybridisation. For detection of donor-type
      endothelial cells after transplantation of haemopoietic stem cells, recipient
      tissue was stained with monoclonal antibodies against donor-type HLA antigens.
      FINDINGS: We identified the BCR/ABL fusion gene in variable proportions (0-56%)
      of endothelial cells generated in vitro. Endothelial cells expressing the fusion
      gene were found in the vascular endothelium of a patient. In a recipient of an
      allogeneic stem-cell transplant, normal donor-type endothelial cells were
      detected in the vascular endothelium. INTERPRETATION: These findings suggest that
      CML is not solely a haematological disease but originates from a bone-marrow
      derived haemangioblastic precursor cell that can give rise to both blood cells
      and endothelial cells. Moreover, normal bone-marrow-derived endothelial cells can
      contribute to the maintenance of the blood vascular endothelium. The integration
      of bone-marrow-derived endothelial cells into the vascular endothelium provides a
      rationale for developing vascular targeting strategies in vasculopathies,
      inflammatory diseases, and cancer.

PMID- 10905247
TI  - Retrospective study of prion-protein accumulation in tonsil and appendix tissues.
AB  - To identify individuals who could be at high risk of developing vCJD, a sensitive
      immunohistochemical technique was used to detect prion protein in a retrospective
      series of over 3000 tonsil and appendix specimens. No positives were detected but
      further studies are required to help reduce uncertainties about possible future
      numbers of vCJD cases in the UK.

PMID- 10905248
TI  - Chlamydia pneumoniae IgG seropositivity and risk of deep-vein thrombosis.
AB  - In a population-based case-control study of 474 patients with a first episode of
      deep-vein thrombosis and 474 age-matched and sex-matched controls, we found no
      effect of Chlamydia pneumoniae infection on the occurrence of deep-vein
      thrombosis.

PMID- 10905249
TI  - Prefabricated vascularised supraclavicular flaps for face resurfacing after
      postburns scarring.
AB  - We have designed a technique for prefabrication of large flaps to cover the whole
      face reconstruction for cervicocephalic postburns scarring. Aesthetic improvement
      and a better quality of life was achieved in all seven patients.

PMID- 10905252
TI  - Sequenced gene boosts Down's syndrome research.

PMID- 10905250
TI  - Longitudinal decline of the neuronal marker N-acetyl aspartate in Alzheimer's
      disease.
AB  - In patients with Alzheimer's disease, but not in health controls, longitudinal
      magnetic resonance spectroscopy shows a striking decline in the neuronal marker,
      N-acetyl aspartate, despite little decline in underlying grey-matter volume.

PMID- 10905251
TI  - Non-penetrance in tuberous sclerosis.
AB  - As a result of extreme clinical variability in tuberous sclerosis, with one well
      documented example of non-penetrance, phenotypically normal siblings or children
      of patients with tuberous sclerosis are thought to be at increased risk of having
      children with the disease. We report that the case of apparent non-penetrance
      that was previously described is the result of two independent tuberous-sclerosis
      mutations in the same family.

PMID- 10905253
TI  - How green is your workout?

PMID- 10905254
TI  - Tanzanian AIDS project works towards "good things for young people".

PMID- 10905255
TI  - WMA drafts guidelines on genetic databases.

PMID- 10905256
TI  - Ireland's infected blood products inquiry begins.

PMID- 10905257
TI  - UK inquiry highlights urgent need for "research governance".

PMID- 10905258
TI  - The blood in systemic disorders.
AB  - * The high rate of proliferation required of the bone marrow renders it highly
      susceptible to the influence of external factors. * Anaemia is the most common
      haematological abnormality seen in systemic disorders. * In the anaemia of
      chronic disease, erythropoietin production is reduced and proliferation of
      erythroid progenitor cells is also impaired; this anaemia can generally be
      alleviated by correction of the underlying disease process. * The status of the
      endocrine system must always be considered in evaluation of a normocytic,
      normochromic anaemia. * Anaemia in infection can be due to host or parasite
      factors or to the treatment administered. * Anaemia due to malignant disease
      responds to erythropoietin therapy in many cases; failure to respond is a poor
      prognostic sign.

PMID- 10905259
TI  - Helmut Ruska and the visualisation of viruses.

PMID- 10905260
TI  - Sustainability, affordability, and equity of corporate drug donations: the case
      of Malarone.

PMID- 10905261
TI  - Awareness during anaesthesia.

PMID- 10905262
TI  - Awareness during anaesthesia.

PMID- 10905263
TI  - Awareness during anaesthesia.

PMID- 10905264
TI  - Awareness during anaesthesia.

PMID- 10905265
TI  - A rockwool fibre worker with lung fibrosis.

PMID- 10905266
TI  - Treatment of pediculosis capitis by dry combing.

PMID- 10905267
TI  - Needless treatment for presumed malignancy.

PMID- 10905268
TI  - Needless treatment for presumed malignancy.

PMID- 10905269
TI  - Needless treatment for presumed malignancy.

PMID- 10905270
TI  - Injections and pain.

PMID- 10905271
TI  - Hormone replacement therapy and mammography.

PMID- 10905272
TI  - Coronary heart disease in Indian Asians.

PMID- 10905273
TI  - Coronary heart disease in Indian Asians.

PMID- 10905274
TI  - Can growth hormone therapy cause diabetes? KIMS Strategic Committee.

PMID- 10905275
TI  - Cervical spatulas.

PMID- 10905276
TI  - School-based screening for STI.

PMID- 10905277
TI  - Science, evidence, and the use of the word scientific.

PMID- 10905278
TI  - Should menstruation be optional for women?

PMID- 10905280
TI  - Methods of analysis

PMID- 10905279
TI  - The Nobel chronicles. 1991 Erwin Neher (b 1944) and Bert Sakman (b 1942).

PMID- 10905282
TI  - DNA screening without PCR.

PMID- 10905281
TI  - Disinfection byproducts in drinking water.

PMID- 10905283
TI  - Chemical mass shifts in ion traps

PMID- 10905284
TI  - Universal on-chip RI detection

PMID- 10905285
TI  - Clinical diagnostics in need of standards.

PMID- 10905286
TI  - Detecting genetically modified products in food.

PMID- 10905287
TI  - Urban air: real samples for undergraduate analytical chemistry.

PMID- 10905288
TI  - Electrokinetic separations for synthetic polymers.

PMID- 10905290
TI  - Diode array detectors for HPLC

PMID- 10905289
TI  - Twenty years of laser research in analytical chemistry

PMID- 10905291
TI  - Does the web work for analytical chemists?

PMID- 10905292
TI  - Control of chemical mass shifts in the quadrupole ion trap through selection of
      resonance ejection working point and rf scan direction
AB  - Compound-dependent chemical mass shifts are observed and their origin is
      elucidated in a modified Finnigan GCQ quadrupole ion trap mass spectrometer. The
      dependence of chemical mass shifts on ion trap geometry, specifically the center
      to end-cap spacing, z0, and the size of the apertures in the end caps, is
      demonstrated. The effects of the working point (qeject value) used for resonance
      ejection and the direction of the rf mass analysis scan are also studied, and the
      results are found to be in agreement with a previously proposed model for the
      chemical mass shift mechanism. It is shown that chemical mass shifts are present
      when resonance ejection is used, unless the qeject is chosen to correspond to a
      nonlinear resonance point, where the shifts are removed. The shifts are also
      removed by performing the mass analysis scan in the reverse direction, i.e., from
      high mass to low mass.

PMID- 10905293
TI  - Techniques for the optimization of proteomic strategies based on head column
      stacking capillary electrophoresis.
AB  - Proteomics is the large-scale study of the proteins related to a genome.
      Presently, proteomic procedures have relied on mass spectrometry as a tool of
      choice to perform analysis of proteins. Optimization and understanding of the
      different steps involved in proteomics using mass spectrometry is expensive and
      time-consuming and, for this reason, have been typically paid insufficient
      attention. However, optimization becomes a critical issue as we try to analyze
      ever shrinking amounts of proteins. We present here the development of a
      technique that allows the rapid, sensitive, semiquantitative, and automated
      optimization of the processes involved in proteomics. Furthermore, it allows the
      rapid testing of new methodologies without having to rely on expensive mass
      spectrometric techniques. The technique, based on head column stacking capillary
      zone electrophoresis, allows the concentration, separation, and analysis of
      protein digests at concentrations from high picomoles to subfemtomoles per
      microliter and sample volumes from a few microliters to a few hundred microliters
      produced by proteomic processes. Furthermore, the incorporation of UV detection
      in the system allows the tracking of the relative changes in peptide levels
      observed during optimization. In addition, all the buffers and solvents used in
      this technique are compatible with its future coupling to electrospray ionization
      mass spectrometry. The potential of this technique for the analysis of low
      abundance proteins is demonstrated using peptide standards and tryptic digests of
      standard proteins. Moreover, we exemplify the application of this technique in
      proteomic prototyping for the rapid and automated study of the procedure of
      enzymatic digestion of proteins.

PMID- 10905294
TI  - Chip-scale universal detection based on backscatter interferometry
AB  - An on-chip detector based on backscatter interferometry has been developed to
      perform subnanoliter-volume refractive index measurements. The detection system
      consists of a simple, folded optical train based on the interaction of a laser
      beam and an etched channel, consisting of two radii joined by a flat portion,
      thus defining a curved surface in the shape of a hemisphere in a silica (glass)
      plate. The backscattered light from the channel takes on the form of a high
      contrast interference pattern that contains information related to the bulk
      properties of the fluid contained within the probe volume. Positional changes of
      the interference pattern (fringes) allow for the determination of deltan at the
      10(-6) level, corresponding to 743 microM or 139 x 10(-15) mol or 12.8 x 10(-12)
      g of sucrose, in a probe volume of only 188 x 10(-12) L. A theoretical model of
      the on-chip backscatter interferometric detector has also been developed,
      evaluated, and found to be in agreement with experimental data. It is shown that
      the model can be used to predict general system performance for changes in the
      optical train such as the chip's wall thickness and channel diameter.

PMID- 10905295
TI  - Iridium-based electrocatalytic systems for the determination of insulin.
AB  - Two electrochemical catalytic systems for the determination of insulin were
      developed. The homogeneous system was based on the oxidation of insulin by chloro
      complexes of iridium(IV). Kinetic studies revealed that the aquation of iridium
      complexes activated them toward the oxidation of insulin in acidic solutions;
      e.g., the rate constant was equal to 25, 900, and 8,400 L mol(-1) s(-1) for the
      oxidation of insulin by the IrCl62-, Ir(H2O)CI5-, and Ir(H2O)2Cl4 complexes,
      respectively. The inertness of the iridium complexes argued for the outer-sphere
      mechanism of the homogeneous oxidation reaction. Electroplating of aquated
      iridium complexes on the glassy carbon electrode resulted in the formation of the
      iridium oxide (IrOx) surface film, which was used in the heterogeneous detection
      system for insulin. The catalytic activity of the IrOx film toward insulin
      oxidation was ascribed to a combination of electron-transfer mediation and oxygen
      transfer which was related to the acid/base chemistry of the film. The IrOx film
      electrode was used as an amperometric detector for flow injection analysis of
      insulin in pH 7.40 phosphate buffer. Linear least-squares calibration curves over
      the range 0.05-0.50 microM (five points) had slopes of 35.2 +/- 0.4 nA microM(-1)
      and correlation coefficients of 0.999. The detection limit for insulin was 20 nM
      using the criterion of a signal of 3 times the peak-to-peak noise. The
      advantageous properties of the detector based on the IrOx film are its inherent
      stability at physiological pH, high catalytic activity toward insulin oxidation,
      and simplicity of preparation.

PMID- 10905296
TI  - Analysis of bile acids and their conjugates by capillary
      electrochromatography/electrospray ion trap mass spectrometry.
AB  - Different macroporous, monolithic capillary columns were prepared to separate
      various bile acid mixtures through capillary electrochromatography (CEC) at high
      efficiency. These columns are shown to be ideally suitable for coupling to an
      electrospray ionization/ion trap mass spectrometer. Detection and structural
      identification of different bile acid derivatives in either the positive- or
      negative-ion mode necessitated column technologies with different polarities and
      the capabilities of a reversed electroosmotic flow. High column efficiencies
      (610,000 theoretical plates/meter for glycocholic acid in normal-phase
      separation) were preserved in the coupling to mass spectrometry (MS), with the
      detection limits of approximately 40 femtomole (for cholic acid) and
      identification through CEC/MS/MS.

PMID- 10905297
TI  - Liquid chromatography/mass spectrometry for timely response in regulatory
      analyses: identification of pentobarbital in dog food.
AB  - A limited liquid chromatography/mass spectrometry (LC/ MS) data set was acquired
      under conditions which called for timely response without benefit of a fully
      developed method. Quality assurance elements verified that an LC/ MS procedure
      developed in a short-time was sufficiently under control to meet its purpose.
      LC/MS was used to rule out a potential problem with a gas chromatography (GC)/MS
      method that had been developed for regulatory purposes. The LC/MS data set showed
      that signals identified by GC/MS as diagnostic of pentobarbital (PB) were not
      artifacts of derivatization or GC analysis. Samples of dry dog food identified by
      GC/MS as containing PB were also shown by LC/MS to contain PB. The LC/MS method
      would not be recommended as a substitute for GC/MS, primarily because of poorer
      sensitivity. Although the data set is limited, and justifiably represents only
      the starting point for conventional method development, the purpose at hand was
      served adequately. This work demonstrates the utility of LC/MS for rapid
      regulatory response, provided there is a framework of quality assurance checks.

PMID- 10905299
TI  - A tandem ion trap/ion mobility spectrometer
AB  - A tandem quadrupole ion trap/ion mobility spectrometer (QIT/IMS) has been
      constructed for structural analysis based on the gas-phase mobilities of mass
      selected ions. The instrument combines the ion accumulation, manipulation, and
      mass-selection capabilities of a modified ion trap mass spectrometer with gas
      phase electrophoretic separation in a custom-built ion mobility drift cell. The
      quadrupole ion trap may be operated as a conventional mass spectrometer, with ion
      detection using an off-axis dynode/multiplier arrangement, or as an ion source
      for the IMS drift cell. In the latter case, pulses of ions are ejected from the
      trap and transferred to the drift cell where mobility in the presence of helium
      buffer gas is determined by the collision cross section of the ion. Ions
      traversing the drift cell are detected by an in-line electron multiplier and the
      data processed with a multichannel scaler. Preliminary data are presented on
      instrumental performance characteristics and the application of QIT/ IMS to
      structural and conformational studies of aromatic ions and protonated amine/crown
      ether noncovalent complexes generated via ion/molecule reactions in the ion trap.

PMID- 10905298
TI  - Relating electrospray ionization response to nonpolar character of small
      peptides.
AB  - Nonpolar regions in biological molecules are investigated as a determining factor
      governing their electrospray ionization (ESI) mass spectrometric response.
      Response is compared for a series of peptides whose C-terminal residue is varied
      among amino acids with increasingly nonpolar side chains. Increased ESI response
      is observed for peptides with more extensive nonpolar regions. The basis for this
      increase is examined by comparing values of nonpolar surface area and Gibbs free
      energy of transfer for the different amino acid residues. Comparisons of response
      with octadecylamine are also made, and this highly surface-active ion is observed
      to outcompete all other analytes in ESI response. These observations are
      rationalized on the basis of the equilibrium partitioning model, which is used
      successfully to fit experimental data throughout the concentration range for
      several two-analyte systems. This model suggests that because excess charge
      exists on ESI droplet surfaces, an analyte's relative affinity for the droplet
      surface determines its relative ESI response. Increased nonpolar character, which
      leads to enhanced affinity for the surface phase, results in more successful
      competition for excess charge and higher ESI response.

PMID- 10905300
TI  - In-membrane preconcentration/membrane inlet mass spectrometry of volatile and
      semivolatile organic compounds.
AB  - The on-line determination of volatile and semivolatile organic compounds (SVOCs)
      is reported using membrane inlet mass spectrometry with in-membrane
      preconcentration (IMP-MIMS). Semivolatile organic compounds in aqueous samples
      are preconcentrated in a flow-through silicone hollow-fiber membrane inlet held
      in a GC oven. The sample stream is replaced with air, and the SVOCs are thermally
      desorbed into the mass spectrometer by rapid heating of the membrane. The method
      is evaluated for the on-line determination of 4-fluorobenzoic acid, 3,5
      difluorobenzoic acid, 2-chlorophenol, p-tert-butylphenol, and dimethyl sulfoxide
      (DMSO) in water. The selectivity of the IMP-MIMS technique for SVOCs in the
      presence of VOCs is demonstrated. Cryotrapping and a rapid gas chromatographic
      separation step were added between the membrane and the mass spectrometer ion
      source for the determination of SVOCs in complex mixtures. The procedure is
      demonstrated for the determination of dimethyl sulfoxide (DMSO) in equine urine,
      using internal standardization with DMSO-d6. Full-scan electron ionization (EI)
      mass spectrometric detection showed good linearity (R = 0.998) and RSDs, relative
      to the internal standard, of 2.2% for desorption only and 4.6% for desorption and
      cryotrapping.

PMID- 10905301
TI  - Mobility labeling for parallel CID of ion mixtures.
AB  - An ion mobility/mass spectrometry technique has been developed to record
      collision-induced dissociation patterns for multiple ions in a parallel fashion.
      In this approach, a mixture of ions is separated in a drift tube on the basis of
      differences in mobilities through a buffer gas. As the ions exit the drift tube,
      they are accelerated into a collision cell and the ensuing fragment ions are
      dispersed by differences in mass-to-charge (m/z) ratios in a time-of-flight mass
      spectrometer. Fragment ions that are formed in the collision cell have drift
      times that are coincident with their antecedent parent ions, allowing the origin
      of all fragments formed from the mixture of ions to be determined. The approach
      is demonstrated by examining fragmentation patterns of the [M + H]+ parent and a
      series of a-, b-, and y-type fragments of [D-Ala2,3]methionine enkephalin.

PMID- 10905302
TI  - Improvements in protein identification by MALDI-TOF-MS peptide mapping.
AB  - A new strategy for identifying proteins in sequence data-bases by MALDI-MS
      peptide mapping is reported. The strategy corrects for systematic deviations of
      determined peptide molecular masses using information contained in the opened
      database and thereby renders unnecessary internal spectrum calibration. As a
      result, data acquisition is simplified and less error prone. Performance of the
      new strategy is demonstrated by identification of a set of recombinant, human
      cDNA expression products as well as native proteins isolated from crude mouse
      brain extracts by 2-D electrophoresis. Using one set of calibration constants for
      the mass spectrometric analyses, 20 proteins were identified without applying any
      molecular weight restrictions, which was not possible without data correction. A
      sequence database search program has been written that performs all necessary
      calculations automatically, access to which will be provided to the scientific
      community in the Internet.

PMID- 10905303
TI  - Characterization by atomic force microscopy of fused-silica capillaries
      chemically modified for capillary electrokinetic chromatography
AB  - Fused-silica capillary tubes with 50-microm bores have been chemically modified
      to yield octadecyl-derivatized surfaces with increased surface area. Alkylation
      is achieved in three steps: etching, silane adlayering, and olefin hydrosilation.
      Surface roughness, surface area, surface-tip attractive forces, and topographic
      images of the native, etched, silane-adlayered, and alkylated capillary bores as
      measured by atomic force microscopy are presented here. Significant roughening
      occurs during the etching process, but the most dramatic change in roughness and
      surface adhesion forces occurs in the hydrided (silane-adlayered) capillary
      surface. Topographic smoothing and passivation of surface activity are observed
      for the alkylated capillary surface.

PMID- 10905304
TI  - Dynamic micellar electrokinetic chromatography. Determination of the
      enantiomerization barriers of oxazepam, temazepam, and lorazepam.
AB  - The temperature-dependent enantiomerization barriers of oxazepam, temazepam, and
      lorazepam have been determined between 0 and 30 degrees C by dynamic micellar
      electrokinetic chromatography (DMEKC) in an aqueous 20 mM borate/phosphate buffer
      system at pH 8 with 60 mM sodium cholate as chiral surfactant. Interconversion
      profiles featuring plateau formation and peak broadening were observed and
      simulated by the new program ChromWin based on the theoretical plate as well as
      on the stochastic model using the experimental data plateau height, hplateau,
      peak width at half-height, wh, total retention times, tR, and electroosmotic
      breakthrough time, t0. Peak form analysis yielded rate constants k and kinetic
      activation parameters, deltaG double dagger, deltaH double dagger, and deltaS
      double dagger, of the enantiomerization of oxazepam, temazepam, and lorazepam. At
      25 degrees C, the enantiomerization barrier, deltaG double dagger, was determined
      to be approximately 90 kJ mol-1 and the half-lives, tau, were determined to be
      approximately 21 min. The new approach allows the fast and precise determination
      of enantiomerization barriers in a biogenic environment and it mimics
      physiological conditions, as no organic modifiers or abiotic chiral stationary
      phases (CSP) are employed.

PMID- 10905305
TI  - Indirect fluorescence detection of amino acids on electrophoretic microchips.
AB  - Microfabricated devices enable rapid separations of a variety of clinically
      significant analytes, including DNA, proteins, and amino acids. However,
      absorbance detection has been difficult to achieve on these devices, prohibiting
      analysis of nonfluorophore-bearing or nonfluorescently tagged analytes. An
      alternative detection technique exploiting indirect fluorescence has been adapted
      to the electrophoretic microchip to provide fast analysis of amino acids,
      bypassing the need for absorbance detection or fluorescence derivitization
      procedures. Nineteen of the standard amino acids could be detected with an
      average detection limit of 32.9 microM (approximately 1.6 amol). Despite the fact
      that the detection sensitivity was lower than that achievable by labeling the
      amino acids with fluorescein isothiocyanate (approximately 1 nM), circumventing
      sample preparation and the difficulties inherent with tagging complex samples
      make this technique attractive for a variety of assays where sensitivity is not
      critical. To demonstrate the applicability to real sample matrixes, the analysis
      of urine with elevated amino acid levels is used as a model system where the
      elevated levels are indicative of a variety of pathologies including amino acid
      metabolism disorders and kidney malfunction. The minimal sample handling and
      rapid separations achievable by employing indirect detection on microchips
      provides the potential for high-throughput applications for certain amino acid
      analyses.

PMID- 10905306
TI  - In-tube solid-phase microextraction coupled to capillary LC for carbamate
      analysis in water samples.
AB  - Recently, the on-line sample preparation technique, intube solid-phase
      microextraction (SPME), was successfully implemented with a Hewlett-Packard 1100
      HPLC system for analysis of carbamates in water samples. This paper describes the
      coupling of in-tube SPME to capillary LC and explores its utility as a sample
      preparation method in that format, relative to conventional LC. The Hewlett
      Packard HPLC system was upgraded to a capillary LC system using commercially
      available accessories from LC Packings. The combination of in-tube SPME with a
      capillary LC system was expected to build on the merits of both in-tube SPME and
      the capillary LC to generate a sensitive method with an easy, effective, and
      efficient sample preparation. Due to the relatively large effective injection
      volume of the in-tube SPME technique (30-45 microL), on-column focusing was
      employed in order to achieve good chromatographic efficiency. Excellent
      sensitivity was achieved with very good method precision. For all carbamates
      studied, the RSD of retention time was between 0.5 and 0.8% under 4 microL/min
      microgradient conditions. The RSD of peak area counts was between 1.5 and 4.6%.
      The detection limits for all carbamates studied were less than 0.3 microg/L and,
      for carbaryl, just 0.02 microg/L (20 ppt). Compared with the conventional in-tube
      SPME/LC method, the LODs were lowered for carbaryl, propham, methiocarb,
      promecarb, chlorpropham, and barban, by factors of 24, 45, 42, 81, 62, and 56,
      respectively. The optimized method was successfully applied to the analysis of
      carbamates in surface water samples.

PMID- 10905307
TI  - Isolation and quantification of dissolved lignin from natural waters using solid
      phase extraction and GC/MS.
AB  - Solid-phase extraction (SPE) was tested for the isolation of dissolved lignin
      from diverse natural waters (fresh, estuarine, and marine) in preparation for CuO
      oxidation. Capillary GC coupled to selected-ion monitoring mass spectrometry (SIM
      MS) of CuO oxidation products provides the high sensitivity and precision
      required for the identification and quantification of trace levels of lignin in
      seawater. The low blanks and quick cleanup of C18 cartridges support SPE for
      processing such samples. Comparison of SPE with other isolation procedures
      (direct dry-down and ultrafiltration) has shown that this method quantitatively
      recovers dissolved lignin and preserves its compositional parameters. The
      concentration and nature of dissolved organic matter appear to be primary factors
      that constrain the amount of water that should be processed to obtain
      quantitative and reproducible recoveries of dissolved lignin using SPE. Highest
      recoveries of dissolved lignin were obtained at low pH (1.5-4.0) with substantial
      decreases at pH > 4. Extraction efficiencies were independent of flow rate within
      a range of five to fifteen bed volumes per minute (50-150 mL min(-1)), and both
      refrigeration and freezing were appropriate long-term storage methods for
      processed cartridges prior to elution of retained dissolved lignin.

PMID- 10905308
TI  - Application of the thermally tuned tandem column concept to the separation of
      several families of environmental toxicants.
AB  - Separations of several families of environmental toxicants were optimized by
      means of the thermally tuned tandem column (T3C) concept. We use a tandem
      combination of an octadecylsilane (ODS) and a carbon-coated zirconia (C-ZrO2)
      column; and tune the selectivity by independently adjusting the isothermal
      temperatures of the two columns. This results in the change in the contribution
      that each column makes to the overall retention and selectivity. The separation
      was optimized by locating the optimum pair of column temperatures which give the
      best separation of the critical solute pair. For both triazine herbicides and
      carbamate pesticides samples, dramatically different selectivities and different
      critical pairs were observed for the two types of phases. Although neither
      individual phase gave adequate separation, the T3C approach provided baseline
      separations using only four preliminary trial separations. We also showed that,
      for the triazine samples, the T3C approach gave a better separation than did
      conventional mobile phase optimization with an ODS column. The combination of
      superior selectivity of T3C and high flow rate allows the baseline separation of
      complex mixtures in just a few minutes.

PMID- 10905309
TI  - Direct temperature-controlled trapping system and its use for the gas
      chromatographic determination of organic vapor released from human skin.
AB  - For controlling of trap temperature, the relationship between electric resistance
      of the trap tube and temperature is used. As the electric resistance of the trap
      tube (20 cm long stainless steel tubing) was very small, such as ca. 0.040 ohm
      for -70 degrees C and ca. 0.064 ohm for +90 degrees C, it was estimated by using
      the value of voltage output at both ends of the trap tube when a direct current
      (5 A) was applied for 6.5 ms at every 100 ms on the trap. By using this
      temperature measurement, a cycle of trapping is shortened, especially at the
      process of desorption, because it is possible to set a large increasing rate of
      temperature, such as 20 degrees C/s. The present trapping system has faster
      temperature response compared to that with a thermocouple. This system was
      applied for the study of the releasing of ethanol and water vapors from the human
      finger, which was treated as follows: dipping in 10% ethanol aqueous solution for
      1 min, followed by washing with water and then drying in the air. In this case, a
      cycle of trapping took 53 s, and the period of total analysis was only 3 min. The
      present system is an efficient tool for the study of the exhalation of organic
      vapors from human skin.

PMID- 10905311
TI  - A Salmonella detection system using an engineered DNA binding protein that
      specifically captured a DNA sequence.
AB  - We have developed a novel method for the detection with high selectivity of a
      double-stranded DNA fragment using an engineered DNA-binding protein, DnaA IV, a
      fusion protein of the DNA-binding domain of DnaA and glutathione S-transferase.
      The DNA fragment detection system is based on DNA-protein interaction and
      consists of sequence-specific binding of DnaA IV with a DNA fragment containing
      the DnaA box. DnaA IV, while not capturing other DNA fragments, specifically
      captured that containing the DnaA box. Because the oriC fragment containing the
      DnaA box could be specifically amplified by PCR from the genus Salmonella, the
      DNA fragment detection system was adapted for the detection of Salmonella. The
      Salmonella detection system using PCR amplification and the engineered DNA
      binding protein could distinguish 104 cfu/mL Salmonella from 106 cfu/ mL
      contaminating bacteria.

PMID- 10905310
TI  - Nonequilibrium solid-phase microextraction for determination of the freely
      dissolved concentration of hydrophobic organic compounds: matrix effects and
      limitations.
AB  - Solid-phase microextraction (SPME) has recently been applied to measure the
      freely dissolved concentration, as opposed to the total concentration, of
      hydrophobic substances in aqueous solutions. This requires that only the freely
      dissolved analytes contribute to the concentration in the SPME fiber coating.
      However, for nonequilibrium SPME the sorbed analytes that diffuse into the
      unstirred water layer (UWL) adjacent to the SPME fiber can desorb from the matrix
      and contribute to the flux into the fiber. These processes were described as a
      model. Experimentally, an equilibrated and disconnected headspace was used as a
      reference for the freely dissolved concentration. The expected contribution of
      desorbed analytes to the uptake flux was measured for PCB no. 52 in a protein
      rich solution, while it was not measured in a matrix containing artificial soil.
      The latter was possibly due to slow desorption of the analyte from the artificial
      soil. On the basis of the present study, a contribution of desorbed analytes to
      the uptake flux is expected only if(1) the rate-limiting step of the uptake
      process is diffusion through the UWL, (2) the concentration of the sorbed analyte
      is high, and (3) desorption from the matrix is fast.

PMID- 10905312
TI  - Feasibility study on the characterization of thin layers by charged-particle
      activation analysis
AB  - The purpose of this feasibility study was to investigate the possibilities and
      limitations of Charged-Particle Activation Analysis (CPAA) as a thin layer
      characterization method, i.e., the determination of the mass thickness or the
      composition of a thin layer. Therefore industrially important layers of sputtered
      Al, AlOx, TiQx (all three from the packaging industry), YBa2Cu3O6+delta, and Y2O3
      stabilized ZrO2 (both superconducting industry) on different substrates were
      analyzed, and thereby the accuracy, the detection limits, and the precision of
      the method were studied. To test the accuracy, the same materials were also
      analyzed with neutron activation analysis (NAA) and inductively coupled plasma
      mass spectrometry (ICPMS). The results of CPAA compared with the results of NAA
      and ICPMS showed no significant difference at the 95% confidence level. The
      detection limits expressed as mass thickness were about 10-2 microg cm-2 or
      expressed as thickness 0.04 nm for a monatomic layer of Al. The experiments
      showed that the precision of the method depends only on the counting statistics.
      Generally we can conclude that CPAA is an absolute method for the
      characterization of "thin" layers, with respect to composition and mass thickness
      determinations.

PMID- 10905313
TI  - Adaptable multivariate calibration models for spectral applications
AB  - Multivariate calibration techniques have been used in a wide variety of
      spectroscopic situations. In many of these situations, spectral variation can be
      partitioned into separate classes. For example, suppose that multiple spectra are
      obtained from each of a number of different objects wherein the level of the
      analyte of interest varies within each object over time. In such situations, the
      total spectral variation observed across all measurements has two distinct
      general sources of variation: intraobject and interobject. One might want to
      develop a global multivariate calibration model that predicts the analyte of
      interest accurately both within and across objects, including new objects not
      involved in developing the calibration model. However, this goal might be hard to
      realize if the interobject spectral variation is complex and difficult to model.
      If the intraobject spectral variation is consistent across objects, an effective
      alternative approach might be to develop a generic intraobject model that can be
      adapted to each object separately. This paper contains recommendations for
      experimental protocols and data analysis in such situations. The approach is
      illustrated with an example involving the noninvasive measurement of glucose
      using near-infrared reflectance spectroscopy. Extensions to calibration
      maintenance and calibration transfer are discussed.

PMID- 10905314
TI  - Photochemically induced energy-transfer effects on the decay times of ruthenium
      complexes in polymers
AB  - The effects of photobleaching on absorption properties and decay times of
      ruthenium complexes adsorbed on silica gel or dissolved in polystyrene or PVC are
      reported. While complexes with bipyridyl ligands adsorbed on silica gel did not
      show any decay time decrease at all, complexes having phenanthroline ligands
      exhibit a significant photodegradation which is manifested not only by a decrease
      in luminescence intensity but also by decay time decrease and specific absorption
      spectral changes. The effects are shown to depend strongly on the oxygen and dye
      concentrations present at the bleaching process. The absorption bands of the
      photoproducts of ruthenium-phenanthroline complexes overlap with the emission
      spectra of the intact molecules. Forster resonance energy transfer from intact
      ruthenium complexes to their own photoproducts, generated by singlet oxygen
      attack of the phenanthroline bridges of the ligands, is suggested to be
      responsible for the observed decay time effects.

PMID- 10905315
TI  - Transport of paramagnetic liquids under nonuniform high magnetic field
AB  - From recent investigations, the magnetic force generated by a heterogeneous high
      magnetic field has been highlighted, in particular by levitating systems. This
      paper is devoted to describing a new method for the analysis of the magnetic
      properties of liquids by using the magnetic force. This technique has consisted
      of observing and measuring the transport of a paramagnetic or diamagnetic liquid
      under the gradient of high magnetic fields. The theoretical approach of this
      phenomenon has been developed taking into account the fluid motion expanding in
      an axially symmetrical magnetic field. From this investigation, a typical
      experiment has been carried out by injecting a small amount of paramagnetic
      copper sulfate solution in a cell settled inside the bore of a superconducting
      magnet. Consequently, the accordance between the experimental results and the
      theoretical expectations has led to the determination of the magnetic
      susceptibility of the solution in a short time.

PMID- 10905316
TI  - Anomaly of 155Gd and 157Gd isotope effects in ligand exchange reactions observed
      by ion exchange chromatography
AB  - The isotope effects of gadolinium in Gd-EDTA ligand exchange system were studied
      by means of ion exchange chromatography. The separation coefficients of
      gadolinium isotopes, epsilon, and the local enrichment factors, beta, were
      calculated from the observed isotopic ratios at the front and rear boundaries of
      the gadolinium adsorption band. Clear mass independent anomalies were observed in
      the isotope effects of 155Gd and 157Gd. The relation between the isotope effects
      of gadolinium isotopes, studied by the three-isotope plot and the separation
      coefficient methods, and the mass of gadolinium isotopes was found to be related
      to the change in the mean square radius of the nuclear charge distribution
      parameter, (r2), of these isotopes, which suggests that the nucleus shape and
      size highly affect the gadolinium isotope effects in chemical exchange reactions.

PMID- 10905317
TI  - Sequential projection pursuit using genetic algorithms for data mining of
      analytical data.
AB  - Sequential projection pursuit (SPP) is proposed to detect inhomogeneities
      (clusters) in high-dimensional analytical data. Such inhomogeneities indicate
      that there are groups of objects (samples) with different chemical
      characteristics. The method is compared with principal component analysis (PCA).
      PCA is generally applied to visually explore structure in high-dimensional data,
      but is not specifically used to find clustering tendency. Projection pursuit (PP)
      is specifically designed to find inhomogeneities, but the original method is
      computationally very intensive. SPP combines the advantages of both methods and
      overcomes most of their weak points. In this method, latent variables are
      obtained sequentially according to their importance measured by the entropy
      index. This involves an optimization step, which is achieved by using a genetic
      algorithm. The performance of the method is demonstrated and evaluated, first on
      simulated data sets, and then on near-infrared and gas chromatography data sets.
      It is shown that SPP indeed reveals more easily information about inhomogeneities
      than PCA.

PMID- 10905318
TI  - Detection of atrazine based on the SPR determination of P450 mRNA levels in
      Saccharomyces cerevisiae.
AB  - We describe a novel method for quantification of atrazine based on detection of
      P450 mRNA levels in Saccharomyces cerevisiae. The selected oligonucleotide probe
      exhibited specificity against P450 mRNA and was successfully immobilized on the
      sensor chip. The mRNA was subsequently quantified by RU change using a SPR
      system. When the cells were disrupted by boiling, mRNA could be measured without
      further purification at reduced sensitivity. This simple technique permits the
      detection of atrazine within 15 min. This rapid and highly sensitive method can
      be used for the detection of atrazine.

PMID- 10905319
TI  - The fractional free volume of the sorbed vapor in modeling the viscoelastic
      contribution to polymer-coated surface acoustic wave vapor sensor responses.
AB  - Surface acoustic wave (SAW) vapor sensors with polymeric sorbent layers can
      respond to vapors on the basis of mass loading and modulus decreases of the
      polymer film. The modulus changes are associated with volume changes that occur
      as vapor is sorbed by the film. A factor based on the fractional free volume of
      the vapor as a liquid has been incorporated into a model for the contribution of
      swelling-induced modulus changes to observed SAW vapor sensor responses. In this
      model, it is not the entire volume added to the film by the vapor that
      contributes to the modulus effect; it is the fractional free volume associated
      with the vapor molecules that causes the modulus to decrease in a manner that is
      equivalent to free volume changes from thermal expansion. The amplification of
      the SAW vapor sensor response due to modulus effects that are predicted by this
      model has been compared to amplification factors determined by comparing the
      responses of polymer-coated SAW vapor sensors with the responses of similarly
      coated thickness shear mode (TSM) vapor sensors, the latter being gravimetric.
      Results for six to eight vapors on each of two polymers, poly(isobutylene) and
      poly(epichlorohydrin), were examined. The model predicts amplification factors of
      the order of about 1.5-3, and vapor-dependent variations in the amplification
      factors are related to the specific volume of the vapor as a liquid. The
      fractional free volume factor provides a physically meaningful addition to the
      model and is consistent with conventional polymer physics treatments of the
      effects of temperature and plasticization on polymer modulus.

PMID- 10905320
TI  - Supersaturated designs for robustness testing
AB  - Supersaturated designs are factorial designs in which the number of factors
      examined exceeds the number of experiments performed. They do not allow an
      estimation of individual effects, since even the main effects are confounded.
      However, the total variance of a response estimated from such a design can in
      principle be used as a measure for the robustness of the method. A number of case
      studies were examined to determine whether the variance estimated from a
      supersaturated design is similar to the one from a Plackett-Burman design. This
      was found to be the case, which means that the estimated variance describes well
      the variation in the response caused by the variation in the factors.

PMID- 10905321
TI  - Integrated potentiometric detector for use in chip-based flow cells
AB  - A new kind of potentiometric chip sensor for ion-selective electrodes (ISE) based
      on a solvent polymeric membrane is described. The chip sensor is designed to trap
      the organic cocktail inside the chip and to permit sample solution to flow past
      the membrane. The design allows the sensor to overcome technical problems of
      ruggedness and would therefore be ideal for industrial processes. The sensor
      performance for a Ba2+-ISE membrane based on a Vogtle ionophore showed
      electrochemical behavior similar to that observed in conventional electrodes and
      microelectrode arrangements.

PMID- 10905322
TI  - High-throughput single-molecule DNA screening based on electrophoresis.
AB  - In electrophoresis, the migration velocity is used for sizing DNA and proteins or
      for distinguishing molecules based on charge and hydrodynamic radius. Many
      protein and DNA assays relevant to disease diagnosis are based on such
      separations. However, standard protocols are not only slow (minutes to hours) but
      also insensitive (many molecules in a detectable band). We successfully
      demonstrated a high-throughput imaging approach that allows determination of the
      individual electrophoretic mobilities of many molecules at a time. Each
      measurement only requires a few milliseconds to complete. This opens up the
      possibility of screening single copies of DNA or proteins within single
      biological cells for disease markers without performing polymerase chain reaction
      or other biological amplification. The purpose is not to separate the DNA
      molecules but to identify each one on the basis of the measured electrophoretic
      mobility. We developed three different procedures to measure the individual
      molecular mobilities. The results correlate well with capillary electrophoresis
      (CE) experiments for the same samples (2-49 kb dsDNA) under identical separation
      conditions. The implication is that any electrophoresis protocols from slab gels
      to CE should be adaptable to single-molecule screening for disease diagnosis.

PMID- 10905323
TI  - Surface characterization of hydroxyapatite and related calcium phosphates by XPS
      and TOF-SIMS.
AB  - The surfaces of six biologically interesting calcium phosphate (CaP) phases
      (hydroxyapatite, dibasic calcium phosphate dihydrate, dibasic calcium phosphate,
      monobasic calcium phosphate, beta-tribasic calcium phosphate, octacalcium
      phosphate) have been examined by X-ray photoelectron spectroscopy (XPS) and time
      of-flight secondary ion mass spectrometry (TOF-SIMS). The intensity of an O(1s)
      shake-up satellite correlates with the phosphate oxygen content. Together with
      the Ca/P and O/Ca XPS peak ratios, this feature helps provide identification of
      the CaP phase(s) present in the surface of unknown samples and establish their
      mole fractions, as proven with a bone sample. Contributions from carbonate
      impurities can be quantified using its C(1s) peak at 279.9 eV and subtracted from
      the O(1s) line shape to aid identification. Principal component analysis (PCA)
      has been applied successfully to analyze TOF-SIMS spectra of these six CaP
      phases. Multivariate analysis can help differentiate these CaP phases using the
      first two PCs, which are dominated by the relative intensities of only a few key
      ions: PO3-, O-, Ca+, CaOH+, PO2-, and OH-.

PMID- 10905324
TI  - Evanescent wave long-period fiber bragg grating as an immobilized antibody
      biosensor.
AB  - An immunosensor using a long-period grating (LPG) was used for sensitive
      detection of antibody-antigen reactions. Goat anti-human IgG (antibody) was
      immobilized on the surface of the LPG, and detection of specific antibody-antigen
      binding was investigated. This sensor operates using total internal reflection
      where an evanescent field interacts with bound antibody immobilized over the
      grating region. The reaction between antibody and antigen altered the LPG
      transmission spectrum and was monitored in real time as a change in refractive
      index, thereby eliminating the need for labeling antigen molecules. Human IgG
      binding was observed to be concentration dependent over a range of 2-100 microg
      mL-1, and equilibrium bound antigen levels could be attained in approximately 5
      min using an initial rate determination. Binding specificity was confirmed using
      human interleukin-2 and bovine serum albumin as controls, and nonspecific
      adsorption of proteins did not significantly interfere with detection of binding.
      Antigen detection in a heterogeneous protein mixture and in crude cell lysate
      from Escherichia coli was also confirmed. Moreover, regeneration of the LPG
      surface via diethylamine treatment resulted in approximately 80% removal of bound
      antigen. Subsequently, fibers reexposed to antigen retained greater than 85% of
      the initial signal after five consecutive regeneration cycles.

PMID- 10905326
TI  - Use of microwave-assisted evaporation for the complete recovery of volatile
      species of inorganic trace analytes
AB  - Solutions must often be evaporated prior to analysis either to preconcentrate the
      analyte or to eliminate an incompatible matrix component. Elimination of the
      halogen-based acids HCI and HF using traditional evaporation methods poses
      recovery problems because of volatilization of the target analyte as the chloride
      or fluoride species. A new sample preparation chemistry for trace analysis, where
      losses of analyte due to volatilization during the evaporation process are
      minimized, is explored using the unique heating mechanisms of the microwave
      assisted evaporation process. The heating mechanisms of hot plate evaporation and
      microwave-assisted evaporation are compared, and temperatures throughout the
      evaporation process using each method are predicted and experimentally verified.
      Because the solution actually cools during microwave-assisted evaporation,
      volatilization due to overheating at dryness is minimized. Elemental standard
      solutions and SRM soil and tissue digestates were evaporated using a hot plate
      method and a newly developed reduced-pressure microwave-assisted evaporation
      apparatus. Redissolution and analysis of the residue by ICPMS showed that
      complete recovery was achieved using microwave-assisted evaporation while losses
      of several classically volatile analytes occurred using hot plate evaporation.

PMID- 10905325
TI  - Combined partial acid hydrolysis and electrospray ionization-mass spectrometry
      for the structural determination of oligosaccharides.
AB  - A general oligosaccharide acid hydrolysis method, amenable to electrospray
      ionization mass spectrometry (ESI-MS), is described that allows for hydrolysis of
      glycosidic bonds for both hexose- and N-acetylhexosamine-containing
      oligosaccharides. The partial acid hydrolysis of oligosaccharides is obtained by
      using an acid-exchange resin as the acid catalyst. A ladder sequence of the
      glycan is produced in solution that is directly analyzed by ESI tandem mass
      spectrometry, employing both ion trap and Fourier transform ion cyclotron
      resonance mass spectrometers, to provide sequence and linkage information. Unlike
      traditional acid hydrolysis procedures, there is minimal degradation of
      monosaccharide residues or deacetylation of N-acetylhexosamines by employing this
      technique. It is further demonstrated that the stereochemistry of the released
      monosaccharides and the anomeric configuration within disaccharides is determined
      by direct derivatization of the hydrolysate with Zn(dien)-Cl2 followed by ESI
      MS/MS.

PMID- 10905327
TI  - Electrochemiluminescence of ruthenium (II) tris(bipyridine) encapsulated in sol
      gel glasses
AB  - The electrogenerated chemiluminescence (ECL) of Ru(bpy)3 2+ and tripropylamine,
      tributylamine, triethylamine, trimethylamine, or sodium oxalate encapsulated
      within sol-gel-derived silica monoliths have been investigated using an
      immobilized ultramicroelectrode assembly. The major purpose of this study was to
      investigate the role of the reductant on the magnitude and stability of the ECL
      in this solid host matrix. For gel-entrapped Ru(bpy)3 2-/tertiary amines, the
      shape and intensity of the ECL-potential curves were highly dependent on scan
      rate. At 10 mV/s, the ECL intensity was ca. 6-fold higher relative to that
      observed at 500 mV/s. When the ECL acquired at low scan rates was normalized by
      that obtained in solution under similar conditions, a value of 0.03-0.06 was
      obtained. In direct contrast, the ECL of the Ru(bpy)3 2+-oxalate system showed
      little dependence on scan rate, and the ECL was ca. 65-75% of that measured in
      solution. These differences can be attributed to differences in rotational and
      translational mobility between the reductants (amines vs oxalate) trapped in this
      porous solid host For both systems, the ECL was found to be stable upon
      continuous oxidation or upon drying the gels in a high-humidity environment for
      over 10 days.

PMID- 10905328
TI  - Electron transfer from diamond electrodes to heme peptide and peroxidase.
AB  - Direct electron transfer from boron-doped diamond electrodes to heme
      undecapeptide and horseradish peroxidase (HRP) was examined and evaluated for the
      application to H2O2 biosensors. As-grown and oxygen plasma-treated diamond
      electrodes on which heme peptide is adsorbed exhibited cathodic current responses
      to H2O2 on the basis of the direct electron transfer. In a comparative study of
      carbon electrodes on which heme peptide was adsorbed, an oxygen plasma-treated
      diamond electrode exhibited responses comparable with those of an edge-oriented
      pyrolytic graphite (EOPG) electrode, despite much smaller roughness. However,
      electron transfer to compounds I and II of HRP from the diamond electrodes was
      much slower than that from EOPG or glassy carbon, suggesting that the pi
      electrons of an sp2 carbon may play an important role in the direct electron
      transfer to the heme moiety of HRP. To examine the applicability of heme peptide
      modified diamond electrodes to oxidase-based biosensors, anodic current responses
      of the oxygen plasma-treated diamond electrode to possible interfering agents,
      ascorbic acid and uric acid, were examined and compared with those of EOPG. Since
      the diamond electrode exhibited much less sensitivity to those interfering
      agents, the heme peptide-modified diamond electrode should be a promising H2O2
      biosensor for the application to oxidase-based biosensors.

PMID- 10905329
TI  - Amperometric immunosensors based on protein A coupled polyaniline
      perfluorosulfonated ionomer composite electrodes.
AB  - A very sensitive immunosensor based on polyaniline/ Nafion/protein A (PA/NF/PrA)
      composite electrodes has been developed for the amperometric immunoanalysis with
      urease-labeled immunoreagents. The use of urease conjugated goat anti-RIgG
      (GaRIgG-Ur) as the labeled antibody and urea as the substrate with an
      amperometric detection at -200 mV (vs Ag/AgCl) resulted in a dynamic range of 50
      2000 ng mL-1 and a low detection limit of 10 ng/mL (64 pM) for the immunoanalysis
      of rabbit immunoglobulin G (RIgG). Because of the special affinity between
      protein A and RIgG, the PA/NF/PrA electrode can be regenerated repetitively by
      changing the pH of the buffer solutions. Characteristics of the PA/NF/PrA/RIgG
      immunosensor and optimal conditions for the competitive immunoanalysis of RIgG
      with FIA were studied.

PMID- 10905330
TI  - Glucose and lactate biosensors based on redox polymer/oxidoreductase
      nanocomposite thin films.
AB  - Glucose and lactate enzyme electrodes have been fabricated through the deposition
      of an anionic self-assembled monolayer and subsequent redox polymer/enzyme
      electrostatic complexation on gold substrates. These surfaces were functionalized
      with a negative charge using 11-mercaptoundecanoic acid (MUA), followed by
      alternating immersions in cationic redox polymer solutions and anionic glucose
      oxidase (GOX) or lactate oxidase (LAX) solutions to build the nanocomposite
      structure. The presence of the multilayer structure was verified by ellipsometry
      and sensor function characterized electrochemically. Reproducible analyte
      response curves from 2 to 20 mM (GOX) and 2-10 mM (LAX) were generated with the
      standard deviation between multiple sensors between 12 and 17%, a direct result
      of the reproducibility of the fabrication technique. In the case of glucose
      enzyme electrodes, the multilayer structure was further stabilized through the
      introduction of covalent bonds within and between the layers. Chemical cross
      linking was accomplished by exposing the thin film to glutaraldehyde vapors,
      inducing linkage formation between lysine and arginine residues present on the
      enzyme periphery with amine groups present on a novel redox polymer,
      poly[vinylpyridine Os(bisbipyridine)2Cl]-co-allylamine. Finally, an initial
      demonstration of thin-film patterning was performed as a precursor to the
      development of redundant sensor arrays. Microcontact printing was used to
      functionalize portions of a gold surface with a blocking agent, typically 1
      hexadecanethiol. This was followed by immersion in MUA to functionalize the
      remaining portions of gold with negative charges. The multilayer deposition
      process was then followed, resulting in growth only on the regions containing
      MUA, resulting in a "positive"-type pattern. This technique may be used for
      fabrication of thin-film redundant sensor arrays, with thickness under 100
      angstrom and lateral dimensions on a micrometer scale.

PMID- 10905331
TI  - Analysis of ternary mixtures with a single dynamic microbial sensor and
      chemometrics using a nonlinear multivariate calibration.
AB  - An amperometric biosensor based on immobilized bacterial cells of Alcaligenes
      eutrophus KT02 and an oxygen electrode was integrated in a flow-through system.
      Because microorganisms metabolize various organic analytes in a specific manner,
      the sensor shows for different pure analytes distinct time-dependent oxygen
      consumption rates that can be treated as characteristic patterns. This behavior
      is conserved also when the biosensor is exposed to a mixture of these organic
      analytes; the sensor with a particular type of microorganisms responds with a
      total signal. The respiration curves as time-dependent amplitudes were subdivided
      into several time channels. This procedure creates an additional data dimension
      and makes the single sensor "dynamic". Using multivariate calibration models with
      only one single biosensor, simultaneous quantitative analysis of ternary mixtures
      of acetate, L-lactate, and succinate was realized. A nonlinear algorithm that
      compensated for conceivable interactions of the analytes was superior to a
      partial least-squares algorithm. Each analyte was predicted more precisely by the
      nonlinear approach resulting in root-mean-square errors of prediction of 0.20
      mg/L for acetate, 0.43 mg/L for L-lactate, and 0.73 mg/L for succinate.

PMID- 10905332
TI  - Electrogenerated chemiluminescence of tris (2,2'-bipyridyl)ruthenium(II) ion
      exchanged in nafion-silica composite films
AB  - The voltammetry and electrogenerated chemiluminescence (ECL) of tris(2,2'
      bipyridyl)ruthenium(II) (Ru(bpy)3 2+) ion-exchanged in Nafion and Nafion-silica
      composite materials have been investigated. The major goal of this work was to
      investigate and develop new materials and immobilization approaches for the
      fabrication of ECL-based sensors with improved reactivity and long-term
      stability. Nation-silica composite materials with varying contents of Nation (53
      100 wt% relative to silica) were prepared via the two-step acid/base hydrolysis
      and condensation of tetramethoxysilane. The Nafion doped sols were spin cast on
      glassy carbon electrodes, dried, and then ion-exchanged with Ru(bpy)3 2+. The
      shapes of the cyclic voltammetric curves and the amount of Ru(bpy)3 2+ exchanged
      into the films strongly depends on the amount of Nafion incorporated into the
      hybrid sol. Nafion-silica films with a low content of Nafion ion-exchanged less
      Ru(bpy)3 2+ and exhibited tail-shaped voltammetry at 100 mV/s. The ECL of
      immobilized Ru(bpy)3 2+ in the presence of either tripropylamine or sodium
      oxalate in pH 5 acetate buffer was also strongly dependent on the amount of
      Nafion introduced into the composite with greater ECL observed for the Nafion
      silica films relative to pure Nafion.

PMID- 10905333
TI  - Ion-induced interfacial dynamics of phospholipid monolayers.
AB  - Ion-induced interfacial dynamics of phospholipid monolayers were studied by
      various electrochemical techniques. The lipid monolayers were constructed by
      using the mercapto derivatives of natural lipids that were self-assembled
      directly onto gold electrode surfaces in a tails-down fashion. The supported
      lipid assemblies appeared to act as rather effective electron-tunneling barriers
      with K3Fe(CN)6 as the redox probe, despite a relatively low surface coverage
      and/or a disordered surface structure. Upon the stimulation by alkaline-earth
      ions, the lipid layers appeared to undergo surface reorganization, exposing part
      of the electrode surface which resulted in the formation of microscopic mass
      transfer lipid channels. The dimensions and/or the number of these channels
      increased with increasing ion concentrations, and this ion-gate effect appeared
      to be quite selective, with the most pronounced effects observed among the series
      of alkaline-earth ions with Ca2+.

PMID- 10905335
TI  - Operation of a miniature redox hydrogel-based pyruvate sensor in undiluted
      deoxygenated calf serum.
AB  - An amperometric sensor for the detection of pyruvate in biological fluids was
      formed by modifying the tip of a 0.25 mm gold wire with a layer of electrically
      "wired" recombinant pyruvate oxidase (POP). The sensor did not require O2 for its
      operation. The electroactive area of the tip of the microwire was increased by
      electrodeposition of platinum black. The POP was adsorbed on the platinum black
      and then "wired" with the cross-linked, subsequently deposited poly(4
      vinylpyridine), part of the pyridine functions of which were complexed with
      [Os(bpy)2Cl](+/2+) and part quaternized with 2-bromoethylamine. In the resulting
      thin layer the POP was well "wired". When the electrode was poised at 0.4 V vs
      Ag/ AgCl, the sensitivity at pH 6 was 0.26 A cm(-2) M(-1) and the current
      increased linearly with the pyruvate concentration through the 2 x 10(-6) - 6 x
      10(-4) M range. Thiamine diphosphate, flavin adenine dinucleotide, and MgCl2 were
      not required for the assay, but stabilized the stored enzyme electrode. Placement
      of a dialysis membrane (MWCO 3500) on the electrode alleviated the severe
      interference of ascorbate. In calf serum, the detection limit was 30 microM,
      suggesting that the electrode might be used in the continuous monitoring of
      pyruvate in hypoxic organs.

PMID- 10905334
TI  - Microcoaxial electrode for in vivo nitric oxide measurement.
AB  - Nitric oxide (NO) is a gaseous mediator involved in various physiological
      phenomena, such as vasorelaxation and neurotransmission. Investigation of local
      cellular responses of NO production in vivo and in vitro requires a measurement
      method with a high spatial resolution. For selective NO measurement, we therefore
      developed a microcoaxial electrode whose tip diameter is less than 10 microm.
      Calibration using various concentrations of NO (0.1-1.0 microM) showed that the
      electrode has good linearity (r = 0.99) and its detection limit is 0.075 microM
      (S/N = 3). We verified the applicability of this electrode to in vivo and in
      vitro local measurement NO released from bovine aortic cultured endothelial cells
      (BAECs) stimulated by acetylcholine (ACh). After the addition of ACh, a transient
      increase in NO concentration was detected by the electrode. In the presence of NG
      nitro-L-arginine methyl ester (L-NAME), a putative NO synthase inhibitor, NO
      release (peak NO concentration) from RAECs was significantly less than that in
      the absence of L-NAME (0.18 +/- 0.04 microM vs 0.47 +/- 0.13; P < 0.01). After
      removal of L-NAME, NO release partially recovered (0.39 +/- 0.10 microM). In
      conclusion, the microcoaxial electrode was successfully applied to direct and
      continuous NO measurement in biological systems.

PMID- 10905336
TI  - Electrochemical and XPS characterization of composite modified electrodes
      obtained by nickel deposition on noble metals
AB  - A chemically modified electrode composed of nickel oxyhydroxide film deposited on
      noble metals (i.e., gold or platinum) was characterized in an alkaline medium by
      cyclic voltammetry and XPS (X-ray photoelectron spectroscopy) techniques. The
      nickel was deposited on the gold substrate in an alkaline medium by various
      strategies: cycling the potential between -0.1 and 0.65 V vs SCE, in
      potentiostatic conditions at potentials comprised between 0.0 and 0.55 V and by
      simple immersion of the electrode in non-deaerated 0.2 M NaOH solutions
      containing 3 mM K2Ni(CN)4. The effects of several experimental parameters such as
      applied potentials, pH, tetracyanonickelate concentration, electrode substrate,
      etc., on the nickel film formation and growth were evaluated. The electroactivity
      of the resulting composite gold-nickel electrode was investigated in an alkaline
      medium toward the oxidation of carbohydrates using arabinose as a model compound.

PMID- 10905337
TI  - Inclusion of phthalate esters by a self-assembled monolayer of thiolated
      cyclodextrin on a gold electrode
AB  - Complexation of phthalic acid esters (PAEs) by a self-assembled monolayer (SAM)
      of thiolated alpha-cyclodextrin (6-(2-mercaptoethylamino)-6-deoxy-alpha
      cyclodextrin, MEA-alpha-CD) on a gold electrode was examined by a cyclic
      voltammetry using hydroquinone (HQ) as a probe. From the inhibitory effect of the
      phthalate esters on the inclusion of HQ by the surface-confined cyclodextrin
      (CD), the association constants (Kasn) of the esters with the immobilized CD were
      estimated. For comparison, the association of PAEs with free alpha-CD was
      examined spectrophotometrically using methyl orange as a probe. It was concluded
      that, in both free and surface-confined CD systems, the Kasn value increased with
      an increase in the length of aliphatic alcohols conjugated to phthalic acid.
      Furthermore, the Kasn values for PAEs in the SAM system were much larger than
      those in a free CD system. This could be intuitively ascribed to the steric
      factor for the PAEs to come out from the cavity of surface-confined CD, whose rim
      was in contact with the PAEs. Thermodynamic parameters indicated that the
      inclusion of PAEs in the SAM system was entropy-driven, which is different from
      the free CD system where the inclusion was favored by both enthalpy and entropy.
      This is partly due to the difficulties in cancellation of strain energy by the
      inclusion into the cavity of the densely fixed CD (97% of the calculated maximum)
      and partly due to the reduction of hydrogen bonding between the PAEs and the
      surface-confined CD. Desolvation of the PAEs and CD by the friction at the
      penetration into the cavity of CD, which was rigidly fixed to the electrode,
      might also contribute to the positive entropy change. These factors might
      emphasize the apolar factor of binding to be characterized by a favorable entropy
      change in the immobilized CD system.

PMID- 10905338
TI  - Intensities of E. coli nucleic acid Raman spectra excited selectively from whole
      cells with 251-nm light.
AB  - Escherichia coli bacteria in the logarithmic growth phase have been investigated
      by UV resonance Raman spectroscopy. Bacterial whole-cell Raman spectra excited at
      251 nm reflect nearly exclusively the nucleic acid composition even though a very
      large fraction of the bacterial mass is composed of protein. It has been
      demonstrated that if bacteria are grown under controlled (logarithmic growth)
      conditions, which give rise to organisms of known average biochemical
      composition, the intensities of E. coli Raman spectra can be explained
      quantitatively from the knowledge of component nucleic acid base resonance Raman
      cross sections.

PMID- 10905339
TI  - Converting spatial to pseudotemporal resolution in laser plasma analysis by
      simultaneous multifiber spectroscopy
AB  - Traditional chemical analysis based on laser plasma spectroscopy (LPS) requires
      time-gated detectors, to avoid the initial signal from the hot plasma. These
      detectors are expensive and often need to be cooled and protected against vapor
      condensation. We suggest a low-cost setup that may replace these gated detectors,
      while maintaining acceptable analytical performance. The proposed setup is a
      result of investigation of plasma-front propagation in LPS analysis. It is known
      that the LPS plasma propagation is similar to the shock wave propagation after a
      strong explosion in the atmosphere. We found that the propagation of the plasma
      fits well the Sedov blast wave theory, providing a good agreement between the
      theoretical and experimental figures. A proper observation geometry, which is
      perpendicular to the plasma expansion vector, enables converting spatial to
      temporal resolution. We take advantage of the fact that the plasma reaches a
      given distance above the analyzed surface at a certain time delay. Therefore, a
      single optical fiber, positioned at a well-defined geometry, can provide spectral
      information corresponding to a certain time delay. A multifiber imaging
      spectrometer provides information corresponding to a series of delay times, which
      is adequate for analysis of a variety of matrixes. It was found that the
      performance of the nongated detector observing a narrow solid angle is similar to
      that of a gated one observing the whole plasma. For one particular example,
      observing the plasma from a distance of 4.5 mm is equivalent to a delay of 4
      micros and integration time of 2 mircos. The ratio of spectral lines of two
      elements was investigated using the spatially resolved (nongated) setup, and it
      was found that this mode is advantageous when internal calibration is applied. It
      was concluded that sensitive LPS analyses can be carried out by less expensive
      (nongated) detectors.

PMID- 10905340
TI  - Integrated system for rapid PCR-based DNA analysis in microfluidic devices.
AB  - An integrated system for rapid PCR-based analysis on a microchip has been
      demonstrated. The system couples a compact thermal cycling assembly based on dual
      Peltier thermoelectric elements with a microchip gel electrophoresis platform.
      This configuration allows fast (approximately 1 min/ cycle) and efficient DNA
      amplification on-chip followed by electrophoretic sizing and detection on the
      same chip. An on-chip DNA concentration technique has been incorporated into the
      system to further reduce analysis time by decreasing the number of thermal cycles
      required. The concentration injection scheme enables detection of PCR products
      after performing as few as 10 thermal cycles, with a total analysis time of less
      than 20 min. The starting template copy number was less than 15 per injection
      volume.

PMID- 10905341
TI  - Measurement of isotopes of light rare earth elements in the form of oxide ions: a
      new development in thermal ionization mass spectrometry
AB  - An isobaric interference free thermal ionization mass spectrometry (TIMS) method
      is presented here for the precise isotope measurements of light rare earth
      elements (LREEs). LREE isotopes can be measured in the form of monoxide ion
      (MO+), but the previous determinations of LREE isotopes in the form of oxide were
      hindered, notably by the 17O and 18O related isobaric interferences. In the
      present study, 16O-enriched oxygen was introduced into the ion source chamber via
      a specially designed gas inlet system. It was observed that the isobaric
      interferences caused by 17O and 18O were remarkably reduced by up to 6 and 70
      times, respectively, compared to those caused by natural oxygen bleeding.
      Isotopic ratios of La, Ce, and Nd obtained without isobaric interference
      corrections show the excellent precision and accuracy in the present study. The
      results also shed some light on the formation mechanism of the measured oxide
      species in TIMS. Furthermore it promises more precise determination of LREE
      abundances and La-Ce and Sm-Nd ages in geochemistry and cosmochemistry.

PMID- 10905342
TI  - Two new families of tandem repeats isolated from genus Vicia using genomic self
      priming PCR.
AB  - A modified genomic self-priming technique was used for rapid isolation of tandem
      repeats from several Vicia species. Based on homologies of their nucleotide
      sequences the newly isolated clones were assigned to two repeat families named
      VicTR-A and VicTR-B. Both families are rich in AT (74%) and are organized as long
      blocks of tandemly repeated units. The VicTR-A repeats are characterized by a
      monomer size of 69 bp, whereas the VicTR-B repeat monomer is about 38 bp long,
      and the two families do not share significant sequence homology. VicTR sequences
      show different degrees of amplification (up to 10(6)-10(7) copies/haploid genome)
      in individual Vicia species and are not amplified in other legumes. The
      abundances of these repeats do not correlate with genome sizes but are similar in
      species that belong to the same taxonomic section within the genus Vicia. Primed
      in situ (PRINS) labeling of metaphase chromosomes of V. pannonica revealed that
      VicTR-A sequences are located predominantly in the telomeric regions of the short
      arms of all chromosomes. In contrast, labeling of VicTR-B repeats in V. sativa
      resulted in mainly intercalary bands of various intensities and only weak
      telomeric signals.

PMID- 10905343
TI  - Characterisation of fission yeast alp11 mutants defines three functional domains
      within tubulin-folding cofactor B.
AB  - The proper folding of tubulins prior to their incorporation into microtubules
      requires a group of conserved proteins called cofactors A to E. In fission yeast,
      homologues of these cofactors (at least B, D and E) are necessary for the
      biogenesis of microtubules and for cell viability. Here we show that the
      temperature-sensitive alp11-924 mutant, which is defective in the cofactor B
      homologue, contains an opal nonsense mutation, which results in the production of
      a truncated Alp11B protein (Alp11(1-118). We isolated a tRNA(Trp) gene as a
      multicopy suppressor of this mutation, which rescues alp11-924 by read-through of
      the nonsense codon. The truncated Alp1-118 protein lacks the C-terminal half of
      Alp11B, consisting of a central coiled-coil region and the distal CLIP-170 domain
      found in a number of proteins involved in microtubule functions. Both of these
      domains are required for the maintenance of microtubule architecture in vivo.
      Detailed functional analyses lead us to propose that Alp11B comprises three
      functional domains: the N-terminal half executes the essential function, the
      central coiled-coil region is necessary for satisfactory maintenance of cellular
      alpha-tubulin levels, and the C-terminal CLIP-170 domain is required for
      efficient binding to alpha-tubulin.

PMID- 10905344
TI  - Transgenic tobacco plants that express an antisense construct derived from a
      Medicago sativa cDNA encoding a Rac-related small GTP-binding protein fail to
      develop necrotic lesions upon elicitor infiltration.
AB  - Using an RT-PCR approach a rac-related cDNA clone, designated Ms-rac1, was
      isolated from Medicago sativa (alfalfa). Ms-rac1 encodes a putative protein of
      197 amino acids, which is closely related to known Rac-related GTP-binding
      proteins from Pisum sativum and Arabidopsis thaliana. RT-PCR analysis
      demonstrated that Ms-rac1 is ubiquitously expressed in various tissues in
      alfalfa. Expression of Ms-rac1 in suspension cultures occurred independently of
      treatment with elicitor, indicating that it is constitutively expressed.
      Heterologous expression of an antisense Ms-rac1 cDNA construct in transgenic
      tobacco plants was associated with poor growth and retarded flowering. Following
      infiltration with yeast elicitor, transgenic tobacco plants transformed with
      either the empty vector or Ms-rac1 in sense orientation developed brown necrotic
      lesions and subsequently cell death was observed within the infiltrated tissues.
      In contrast, the majority of the antisense transformants neither formed necrotic
      lesions nor showed any other visible defence reactions, demonstrating that Rac
      related GTPases play an important role in the establishment of plant defence
      reactions.

PMID- 10905345
TI  - SUMO conjugation and deconjugation.
AB  - Ligation of the ubiquitin-like protein SUMO (Smt3p) to other proteins is
      essential for viability of the yeast Saccharomyces cerevisiae. Like ubiquitin
      (Ub), SUMO undergoes ATP-dependent activation by a specific activating enzyme.
      SUMO-activating enzyme is a heterodimer composed of Uba2p and Aos1p, polypeptides
      with sequence similarities, respectively, to the C- and N-terminal parts of Ub
      activating enzyme. To study the function of SUMO conjugation, we isolated uba2
      mutants that were temperature-sensitive for growth. In these mutants conjugation
      of SUMO to other proteins was drastically reduced, even at the temperature
      permissive for growth. In a screen for spontaneous suppressors of the temperature
      sensitive growth phenotype of the mutant uha2-ts9, we isolated a strain with a
      null mutation (sut9) in a gene of hitherto unknown function (SUT9/YIL031W/SMT4).
      This gene encodes a protein with similarities to Ulp1p, a dual-function protease
      that processes the SUMO precursor and deconjugates SUMO from its substrates. The
      novel protein was therefore termed Ulp2p. Inactivation of ULP2 in a strain
      expressing wild-type SUMO-activating enzyme resulted in slow and temperature
      sensitive growth, and accumulation of SUMO conjugates. Thus, mutations in SUMO
      activating enzyme and mutations in Ulp2p suppress each other, indicating that
      SUMO conjugation and deconjugation must be in balance for cells to grow normally.
      Other phenotypes of ulp2 mutants include a defect in cell cycle progression,
      hypersensitivity to DNA damage, and chromosome mis-segregation. Ulp2p is
      predominantly located within the nucleus, whereas Ulp1p colocalizes with nuclear
      pore complex proteins, indicating that the apparently distinct functions of the
      two SUMO deconjugating enzymes are spatially separated.

PMID- 10905346
TI  - Telomere-based neo-Darwinian selection of yeast clonal subpopulations.
AB  - In Saccharomyces cerevisiae, imbalance of the genes coding for the
      heterochromatin components Sir3p and histone H4 (namely, overdosage of SIR3 and
      lack of one of the two genes coding for H4) causes modifications in telomere
      length and telomere sequence organization, favoring the insertion of Y' elements
      into a stably shortened (C1-3A)n repeat tract. We report here that the newly
      inserted Y' elements are unstable and are lost with high frequency, generating
      clonal subpopulations with short telomeres, as revealed by the analysis of a
      specific telomere (LIII) and of the overall population of telomeres. Moreover,
      the growth rates of the subpopulations with and without Y' elements on LIII are
      different, the Y'-less individuals reproducing 20% more slowly than individuals
      bearing Y' elements. When grown together with Y'-bearing individuals, the
      subpopulations with the normal LIII telomere (which are viable and genetically
      stable if grown alone) are rapidly competed out. Hence, genetic imbalance for the
      structural components of heterochromatin results in a complex and rapidly
      changing mixture of subpopulations in such cultures. Thus, in situations where
      subpopulations are allowed to compete, heterochromatin-based differential growth
      rates result in neo-Darwinian clonal selection.

PMID- 10905347
TI  - The high oleate trait in the cultivated peanut [Arachis hypogaea L.]. I.
      Isolation and characterization of two genes encoding microsomal oleoyl-PC
      desaturases.
AB  - Plant oils rich in oleate are considered superior products compared to oils rich
      in polyunsaturated fatty acids. Peanut (Arachis hypogaea L.) is one of the major
      oilseed crops, and high oleate mutant varieties with as much as 85% oleate have
      been reported. We examined the possibility that this mutant phenotype resulted
      from reduction in the activity or the transcript level of microsomal oleoyl-PC
      desaturase. Two independently generated high oleate mutants, M2-225 and 8-2122,
      and their partially isogenic lines with a normal oleate phenotype were used in
      this study. Two cDNA sequences coding for microsomal oleoyl-PC desaturases,
      ahFAD2A and ahFAD2B, have been isolated from the developing peanut seed with a
      normal oleate phenotype. Cultivated peanut is an allotetraploid, and sequence
      comparisons with the genes from the putative diploid progenitor species suggested
      that ahFAD2A and ahFAD2B are non-allelic, but homeologous genes originating from
      two different diploid species. Northern analysis showed that the transcripts of
      oleoyl-PC desaturases are highly abundant in both normal and high oleate peanut
      seeds in the second stage of development. Differential digestion of the RT-PCR
      products revealed a restriction site polymorphism between ahFAD2A and ahFAD2B,
      and allowed us to examine the level of transcript expressed from each gene. The
      results indicate that ahFAD2A is expressed in both normal and high oleate peanut
      seeds, but the steady state level of the ahFAD2B transcript is severely reduced
      in the high oleate peanut varieties. These data suggested that the reduction in
      ahFAD2B transcript level in the developing seeds is correlated with the high
      oleate trait.

PMID- 10905348
TI  - The high oleate trait in the cultivated peanut [Arachis hypogaea L]. II.
      Molecular basis and genetics of the trait.
AB  - A peanut variety with high oleate content has previously been described. When
      this high oleate variety was used in breeding crosses, the F2 segregation ratio
      of high oleate to normal oleate progeny was 3:1 or 15:1 depending on the normal
      oleate varieties used in the crosses. These data suggested that the high oleate
      trait is controlled by two recessive genes, and some peanut varieties differ from
      the high oleate variety by mutations in one gene, while others differ by
      mutations in two genes. The objective of this study was to understand the
      molecular nature of the high oleate trait and the various segregation patterns.
      In the previous paper in this issue, we reported that the level of transcripts
      expressed by one (ahFAD2B) of two homoeologous genes for oleoyl-PC desaturases in
      cultivated peanut is significantly reduced in high oleate varieties. In this
      report, we examined gene expression by RT-PCR/restriction digestion in a cross
      that shows a one-gene segregation pattern for the high oleate trait. Our data
      showed that the severely reduced level of ahFAD2B transcript correlates
      absolutely with the high oleate phenotype in this cross, suggesting that the
      single gene difference is correlated with the ahFAD2B transcript level. When we
      tested the enzyme activity of the proteins encoded by ahFAD2A and ahFAD2B by
      expression of the cloned sequences in yeast, only the ahFAD2B gene product showed
      significant oleoyl-PC desaturase activity. These data, combined with the
      observation that ahFAD2A shows a change (D150N) in a residue that is absolutely
      conserved among other desaturases, raised the possibility that the ahFAD2A in
      these normal and high oleate lines is a mutant allele. In support of this
      hypothesis, we found that another ahFAD2A allele in a normal oleate peanut line
      does not have the D150N change. This peanut line displays a two-gene-segregation
      pattern for the high oleate trait. In conclusion, our results suggest that a
      mutation in ahFAD2A and a significant reduction in levels of the ahFAD2B
      transcript together cause the high oleate phenotype in peanut varieties, and that
      one expressed gene encoding a functional enzyme appears to be sufficient for the
      normal oleate phenotype.

PMID- 10905350
TI  - Genomic analysis of the vitellogenin locus in rainbow trout (Oncorhynchus mykiss)
      reveals a complex history of gene amplification and retroposon activity.
AB  - Vitellogenins (Vtg) are the major yolk proteins in most oviparous organisms. They
      are encoded by a small number of genes--between one and four depending on the
      species. Characterization of the Vtg region in the genome of the rainbow trout
      reveals unusual features, however, in that this locus contains twenty complete
      genes and ten pseudogenes per haploid genome. The Vtg genes differ from each
      other by insertion, deletion and rearrangement events, although, at the sequence
      level, they show a high degree of similarity. Fluorescent in situ hybridization
      (FISH), pulsed-field gel electrophoresis (PFGE) and Southern analysis indicate
      that all gene copies are contained in a single 1,500-kb region, and that most of
      the genes form tandem arrays separated by a conserved 4.5-kb intergenic region.
      The presence of large reiterated fragments indicates that this region has been
      subjected to several amplification events. The presence of a retroposon element
      (called 19) in Vtg intron 9 appears to be responsible for the silencing of at
      least nine of the ten pseudogenes. Two other incomplete retrotransposons (one LTR
      and one LINE-type) and sequences derived from a HIV-like retrovirus are inserted
      into the conserved intergenic region, very close to the transcription start site.
      Their presence in all Vtg 5'-flanking regions suggests a possible role in gene
      amplification at this locus.

PMID- 10905349
TI  - MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV-
      and methylation-induced DNA damage in Saccharomyces cerevisiae.
AB  - The gene MUS81 p6ethyl methansulfonate, UV sensitive) was identified as clone 81
      in a two-hybrid screen using the Saccharomyces cerevisiae Rad54 protein as a
      bait. It encodes a novel protein with a predicted molecular mass of 72,316 (632
      amino acids) and contains two helix-hairpin-helix motifs, which are found in many
      proteins involved in DNA metabolism in bacteria, yeast, and mammals. Mus81p also
      shares homology with motifs found in the XPF endonuclease superfamily. Deletion
      of MUS81 caused a recessive methyl methansulfonate- and UV-sensitive phenotype.
      However, mus81delta cells were not significantly more sensitive than wild-type to
      gamma-radiation or double-strand breaks induced by HO endonuclease. Double mutant
      analysis suggests that Rad54p and Mus81p act in one pathway for the repair of, or
      tolerance to, UV-induced DNA damage. A complex containing Mus81p and Rad54p was
      identified in immunoprecipitation experiments. Deletion of MUS81 virtually
      eliminated sporulation in one strain background and reduced sporulation and spore
      viability in another. Potential homologs of Mus81p have been identified in
      Schizosaccharomyces pombe, Caenorhabditis elegans and Arabidopsis thaliana. We
      hypothesize that Mus81p plays a role in the recognition and/or processing of
      certain types of DNA damage (caused by UV and MMS) during repair or tolerance
      processes involving the recombinational repair pathway.

PMID- 10905351
TI  - Homologous recombination and allele replacement in transformants of Fusarium
      fujikuroi.
AB  - The ascomycete Fusarium fujikuroi could be transformed stably to hygromycin
      resistance only when the transforming plasmid contained a fragment of DNA from
      the fungus. The transformation frequencies were roughly independent of the
      sequence of the particular fungal DNA fragment used, of its size (1.8 or 6 kb),
      and of whether this DNA was present only once in the fungal genome or about forty
      times (the genes for ribosomal RNA). The plasmid was integrated into the fungal
      genome by homologous recombination in the eighteen transformants tested; ectopic
      integration was never observed. The carB gene of F. fujikuroi was cloned and
      shown to complement unpigmented mutants deficient in phytoene dehydrogenase. A
      mutant carB allele was prepared in vitro and used to transform wild-type
      protoplasts; the transformants contained a genomic duplication and were
      heterozygous for carB; the mutant allele replaced the original wild-type allele
      when this was spontaneously lost in the transformants. This loss was due to gene
      conversion in some cases and to recombination between repeated sequences in
      others.

PMID- 10905352
TI  - Relocation of a cytoplasmic yeast linear plasmid to the nucleus is associated
      with circularization via nonhomologous recombination involving inverted terminal
      repeats.
AB  - The linear plasmid pCLU1 from the yeast Kluyveromyces lactis normally replicates
      in the cytoplasm, with the aid of the helper linear plasmid pGKL2, using terminal
      protein (TP) as a primer. However, it relocates to the nucleus when selection is
      applied for the expression of a plasmid-borne nuclear marker. Migration to the
      nucleus occurred in K. lactis at a frequency of about 10(-3)/cell ten or more
      times higher than the rate observed in Saccharomyces cerevisiae. The nuclear
      plasmids existed only in a circularized form in K. lactis, while in S. cerevisiae
      a telomere-associated linear form is also found. Sequence analysis showed that
      circularization in K. lactis was caused by non-homologous recombination between
      the inverted terminal repeat (ITR) at the ends of the linear form and non
      specific internal target sites in pCLU1. No sequence similarity existed among the
      junction sites, indicating that the free ITR end plays a crucial role in
      circularization. In S. cerevisiae, circular plasmids were generated not only by
      nonhomologous recombination, but also by homologous recombination between short
      direct repeats within pCLU1. Circularization via the ITR end was observed
      independently of RAD52 activity. Sequences highly homologous to ARS core
      elements, 5'-ATTTATTGTTTT-3' for K. lactis and 5'-(A/T)TTTAT(T/G)TTT(A/T)-3' for
      S. cerevisiae, were detected at multiple sites in the nuclear forms of the
      plasmids.

PMID- 10905353
TI  - Structure-function relationships in replication origins of the yeast
      Saccharomyces cerevisiae: higher-order structural organization of DNA in regions
      flanking the ARS consensus sequence.
AB  - In order to better understand the involvement of the DNA molecule in the
      replication initiation process we have characterized the structure of the DNA at
      Autonomously Replicating Sequences (ARSs) in Saccharomyces cerevisiae. Using a
      new method for anti-bent DNA analysis, which allowed us to take into account the
      bending contribution of each successive base plate, we have investigated the
      higher-order structural organization of the DNA in the region which immediately
      surrounds the ARS consensus sequence (ACS). We have identified left- and right
      handed anti-bent DNAs which flank this consensus sequence. The data show that
      this organization correlates with an active ACS. Analysis of the minimum
      nucleotide sequence providing ARS function to plasmids reveals an example where
      the critical nucleotides are restricted to the ACS and the right-handed anti-bent
      DNA domain, although most of the origins considered contained both left- and
      right-handed anti-bent DNAs. Moreover, mutational analysis shows that the right
      handed form is necessary in order to sustain a specific DNA conformation which is
      correlated with the level of plasmid maintenance. A model for the role of these
      individual structural components of the yeast replication origin is presented. We
      discuss the possible role of the right-handed anti-bent DNA domain, in
      conjunction with the ACS, in the process of replication initiation, and
      potentialities offered by the combination of left- and right-handed structural
      components in origin function.

PMID- 10905354
TI  - The tryptophan synthase-encoding trpB gene of Aspergillus nidulans is regulated
      by the cross-pathway control system.
AB  - The tryptophan synthase-encoding gene, trpB, of Aspergillus nidulans was cloned
      and characterized. It was mapped to chromosome I, between the gene medA, which is
      required for sexual and asexual development, and an ORF encoding a protein with
      significant similarity to subunit B of vacuolar ATP synthases. The 5'
      untranslated region was found to be at least 142 nucleotides (nt) long, the
      poly(A) addition site was localized at position + 216 relative to the stop codon
      by sequencing of several independent cDNA clones. The trpB gene contains two
      exons separated by an intron of 105 nt, which is located close to the 5' end of
      the ORF. Directly upstream of the transcriptional start site, one well conserved
      potential binding site for the cross-pathway control transcriptional activator
      CPCA was found. The level of trpB transcript was shown to be regulated by cross
      pathway control. A knockout mutant for trpB displays tryptophan auxotrophy, no
      trpB transcript is detectable, and development is perturbed to an extent that is
      dependent on the amount of tryptophan added to the medium. The trpB gene encodes
      a protein of 723 amino acids, with a calculated molecular weight of 77.6 kDa. The
      deduced amino acid sequence shows 72.6% similarity to the tryptophan synthase of
      Neurospora crassa. Most amino acid residues essential for catalytic activity in
      the tryptophan synthase of Salmonella typhimurium are conserved. The linker
      region joining the two domains of the enzyme is 13 residues longer than the
      longest connector found so far in tryptophan synthases from fungi.

PMID- 10905356
TI  - Developments in bioartificial liver research: concepts, performance, and
      applications.
AB  - As an alternative to liver transplantation, numerous researchers have been
      working toward the goal of development of a fully functional artificial liver. In
      recent years, artificial liver support systems have been advocated as interim
      treatments for patients awaiting hepatocyte replacement therapy or liver
      transplantation; so-called "bridging" treatments. It is recognized that an
      effective artificial liver system requires: (1) a viable and highly functional
      hepatocyte cell line, (2) a suitable bioreactor environment and peripheral
      control systems, and (3) an effective extracorporeal circulatory system to
      incorporate an artificial liver system. Conventional systems have, however,
      suffered from various drawbacks, including incompatibility of cell cultures
      derived from non-human cells, insufficient cell proliferation, rapid
      deterioration of cellular function due to an impoverished cellular environment,
      and lack of system scalability. A newly established artificial liver system
      overcomes many of these problems and demonstrates a long-term capacity to
      maintain multiple liver-specific functions, such as protein synthesis, enzyme
      activity, and drug metabolism, both quantitatively and qualitatively. The present
      review provides an overview of the concepts underpinning artificial liver
      systems, the performance of presently available systems and the practical
      applications of available systems and those in development.

PMID- 10905355
TI  - Characterization of staurosporine-sensitive mutants of Saccharomyces cerevisiae:
      vacuolar functions affect staurosporine sensitivity.
AB  - Mutations at several loci affect the sensitivity of the yeast Saccharomyces
      cerevisiae to staurosporine. We report here the characterization of novel
      staurosporine- and temperature-sensitive mutants (stt). Cloning and integration
      mapping showed that the genes STT2/ STT6, STT5, STT7, STT8 and STT9 are allelic
      to VPS18, ERG10, GPI1, VPS34 and VPS11, respectively. The products of ERG10 and
      GPI1, respectively, catalyze mevalonate and glycosyl phosphatidylinositol anchor
      synthesis, while VPS18 and VPS11 genes belong to the class C VPS (Vacuolar
      Protein Sorting) genes, and the VPS34 gene is classified as a class D VPS.
      Therefore, staurosporine sensitivity is affected by ergosterol and glycolipid
      biosynthesis and by vacuolar functions. We found that other vps mutants belonging
      to classes C and D exhibit staurosporine sensitivity, and that they show calcium
      sensitivity and fail to grow on glycerol as the sole carbon source; both of the
      last two characteristics are shared by vacuolar H+-ATPase mutants (vma). As vma
      mutants were also found to show staurosporine-sensitive growth, staurosporine
      sensitivity is likely to be affected by acidification of the vacuole. Moreover,
      wild type yeast cells are more sensitive to staurosporine in alkaline media than
      in acidic media, suggesting that staurosporine is exported from the cytosol by
      H+/drug antiporters. Pleiotropic drug resistance (PDR) genes also provide some
      resistance to staurosporine, because deltapdr5, deltasnq2 and deltayor1 strains
      are more sensitive to staurosporine than the wild-type strain. This suggests that
      staurosporine is also exported by the ATP-binding cassette (ABC) transporters on
      the plasma membrane. vma mutants and vps mutants of classes C and D vps are
      sensitive to hygromycin B and vanadate, while ABC transporter-depleted mutants do
      not show such sensitivity, indicating that two systems differ in their ability to
      protect the cell against different types of drug.

PMID- 10905357
TI  - Effects of ecabet sodium on experimentally induced reflux esophagitis.
AB  - We investigated the effects of ecabet sodium on experimentally induced reflux
      esophagitis in rats. Three groups of rats, i.e., a control group, esophagitis
      group, and an ecabet sodium group (25mg/kg given twice daily) were used. The
      number of animals which developed esophagitis, the extent of the lesions, and the
      esophagitis lesion index were assessed 3 weeks after the start of the experiment,
      and the lesions were evaluated histopathologically. All nine surviving rats in
      the esophagitis group developed esophagitis, and the esophagitis lesion index was
      32.6 +/- 7.2 (mean +/- SE) per animal. Histopathologically, thickening of the
      epithelium, elongation of papillae of the lamina propria into the epithelium, and
      infiltration of the lamina propria by lymphocytes, eosinophils, plasmacytes, and
      neutrophils, were observed. Interruption of the lamina of the muscularis mucosae
      was also observed, and there was marked proliferation of collagen fibers in the
      submucosa and lamina propria. In the ecabet sodium group, esophagitis developed
      in five of the nine surviving animals (55.6%), but the esophagitis lesion index
      was 1.89 +/- 0.73 per animal, which was significantly lower than that in the
      esophagitis group. The histopathological changes in the rats which developed
      esophagitis were milder in the ecabet sodium group than in the esophagitis group.
      These results suggest that ecabet sodium could be useful for the prevention of
      reflux esophagitis.

PMID- 10905358
TI  - Autofluorescence in indomethacin-induced gastric mucosal lesions in rats.
AB  - Autofluorescence observations enable scientists to sensitively identify various
      lesions. Non-steroidal anti-inflammatory drugs such as aspirin and indomethacin
      are well known to induce gastric mucosal injuries. Our purpose was to clarify
      whether the observation of mucosal autofluorescence could help us to recognize
      indomethacin-induced gastric lesion formation. Gastric mucosal fluorescence
      intensity and gastric lesion scores were time-sequentially measured after
      indomethacin treatment in rats. To identify the localization of autofluorescent
      substances, stomach cryosections were observed with an epifluorescence
      microscope. Fluorescent substances from damaged tissue were also analyzed by high
      performance liquid chromatography. In addition, to elucidate whether oxidative
      stress directly generates fluorescent substances from heme, we investigated the
      reaction between hydrogen peroxide and hemoglobin in a cell-free system.
      Treatment with indomethacin induced gastric lesions by tissue peroxidation, with
      mucosal fluorescence intensity increasing time-dependently. The fluorescence
      products were mesoporphyrin and protoporphyrin, and they were localized in
      disrupted mucosal tissue. In the cell-free system, porphyrins were directly
      generated by hydrogen peroxide from hemoglobin. These findings indicate that
      indomethacin treatment increased the intensity of porphyrin fluorescence. Gastric
      mucosal lesion formation can be sensitively detected with fluorescence
      observations.

PMID- 10905359
TI  - Low-power laser therapy for gastrointestinal neoplasia.
AB  - The purpose of this study was to evaluate changes in the degree of neoplasia
      induced stenosis and clinical symptoms before and after therapy with a contact
      low-power neodymium yttrium aluminum garnet (Nd:YAG) laser. Fifty patients with
      pathologically proven gastrointestinal (GI) neoplasia were studied; 21 with
      benign lesions and 29 with malignant tumors. The low-power contact Nd:YAG laser
      was applied toward the lesion, using an antegrade method as the scope was moved
      circumferentially and downward along the length of the lesions, step-by-step. The
      energy of the laser was 20W, with a duration of 1 to 2 min for each shot. Either
      the tumor was eradicated completely, or the neoplasia-induced stenosis was
      recanalized by laser via the endoscope. All benign lesions were completely
      remitted by laser therapy. The clinical symptoms in the 29 patients with
      malignant GI neoplasia showed a significant improvement (P < 0.001; Wilcoxon
      matched-pairs signed-rank test, one-tailed) after laser therapy in comparison
      with the symptoms before treatment. Malignant GI stenosis treated by laser
      resulted in recanalization in 93.1% of the 29 patients. Unfortunately, in 1
      patient with gastric cancer, the disease progressively worsened after treatment.
      One of 3 patients with early cancer of the stomach who received laser therapy was
      found to have distant metastasis 2 years later. A patient with esophageal cancer
      developed an esophagobronchial fistula that was not a direct complication of the
      laser effect. Four patients with malignancies died of cancer progression during
      the 2 years of follow-up. We conclude that the low-power contact laser is a safe,
      convenient method for the treatment of both benign and malignant tumors. Patients
      with advanced obstructive lesions have a better quality of life after laser
      therapy.

PMID- 10905360
TI  - Early feeding after oncological colorectal surgery in Japanese patients.
AB  - We aimed to determine the safety and feasibility of an alternative postoperative
      oral intake protocol for Japanese patients who had had oncological colorectal
      surgery, with the goal of shortening the length of postoperative stay to the same
      level as that in Western countries. The subjects of the study were 42 consecutive
      patients who underwent elective oncological colorectal surgery. Two protocols.,
      Japanese traditional management (TM: n = 20) and alternative management (AM; n =
      22), were employed. The two protocols differed in their management of oral intake
      after surgery. Tolerance of the alternative protocol and the incidence of
      postoperative complications were determined. The mean length of postoperative
      stay in the AM and TM groups was 11.5 +/- 1.2 and 24.0 +/- 2.1 days, respectively
      (P < 0.0001; t-test). Analysis of the patients who underwent open operation also
      revealed that the length of postoperative stay was less in the AM group than in
      the TM group (12.3 +/- 1.7 and 24.7 +/- 2.2 days, respectively, P = 0.0003). One
      patient in the TM group developed small bowel obstruction during the introduction
      of oral intake. One patient in the AM group also developed small bowel
      obstruction, after discharge. and was readmitted. Other patients tolerated both
      the TM and AM protocols. Morbidity in the AM group was 20.0%, and that in the TM
      group was 30.0% (P = 0.72). The employment of an alternative postoperative oral
      intake protocol was safe and feasible for Japanese patients. Further
      investigation is needed to determine the possible benefits, both medical and
      socioeconomic, of this approach.

PMID- 10905361
TI  - Carcinoma of the splenic flexure: multivariate analysis of predictive factors for
      clinicopathological characteristics and outcome after surgery.
AB  - The clinicopathological characteristics and outcome of splenic flexure cancer
      after surgery have yet to be fully elucidated. The aim of the current study was,
      therefore, to establish predictive factors related to splenic flexure cancer and
      outcome after surgery. We compared the clinicopathological characteristics and
      outcome of 34 patients with splenic flexure cancers (which represents 3.7% of the
      total number of colon cancers in our series) with those of 418 patients with
      right colon and 475 patients with left colon cancers by univariate and
      multivariate analyses, using logistic regression analysis and Cox's proportional
      hazards model. Splenic flexure cancers had a high risk of obstruction (26.5% of
      patients), and had a more advanced stage and lower cure rate than left colon
      cancers. Logistic regression analysis revealed that two independent factors,
      colonic obstruction and the presence of distant metastases, were related to the
      splenic flexure tumor site. Splenic flexure cancer patients had a poorer outcome
      than those with left colon cancer (P = 0.0361). However, there was no difference
      in survival between patients with splenic flexure, those with right colon cancer
      and those with left colon cancer who underwent curative surgery. Cox's regression
      analysis revealed that neither the site of splenic flexure nor colonic
      obstruction was an independent prognostic factor. In conclusion, splenic flexure
      cancer is characterized by a high risk of obstruction and the presence of distant
      metastases. However, after curative resection, splenic flexure cancer has a
      similar outcome to colon cancer at other sites. In addition, neither the splenic
      flexure site nor colonic obstruction had an independent influence on patient
      survival after surgery.

PMID- 10905362
TI  - Comparison of the efficacy of 400mg and 800mg of clarithromycin used with
      lansoprazole and amoxicillin in eradication regimens for Helicobacter pylori
      infection in a Japanese population.
AB  - We conducted a randomized prospective comparative study to determine whether a 1
      week lansoprazole-amoxicillin-clarithromycin (LAC) regimen with 800 mg of
      clarithromycin a day was more effective such a regimen with 400 mg daily in the
      Japanese population. One hundred and seventy-five Helicobacter pylori-positive
      patients were randomly assigned to receive one of two different 7-day regimens,
      one with clarithromycin 400 mg (LAC 400 regimen) and the other with
      clarithromycin 800 mg (LAC 800 regimen). The cure rates for both regimens were
      similar, although adverse effects were significantly more frequent in the LAC 800
      regimen, suggesting that 400 mg of clarithromycin may be sufficient in our
      patient population.

PMID- 10905363
TI  - Papillary serous carcinoma of the peritoneum: analysis of clonality of peritoneal
      tumors.
AB  - Papillary serous carcinoma of the peritoneum (PSCP) is a primary neoplasm of
      peritoneal origin, and is histologically difficult to differentiate from
      papillary serous carcinoma of the ovary (PSCO). PSCP is frequently accompanied by
      many peritoneal tumors, and has been managed as a disseminated disease. In
      previous reports, however, the clonality of the tumors has not been fully
      discussed. Recently, the significant roles of the p53 and BRCA1 genes in PSCP
      have been reported. In this study, we investigated immunohistochemical staining
      for p53 proteins, and investigated p53 gene mutations, using DNA sequencing
      analysis, to clarify the clonality of PSCP tumors. Immunohistochemically, all the
      tumor samples demonstrated nuclear overexpression of p53 proteins, and the DNA
      sequencing analysis of the p53 gene showed diverse point mutations at codons 167
      and 192 in two of four anatomically different tumors. In conclusion, the
      possibility of polyclonality of PSCP tumors is suggested.

PMID- 10905364
TI  - Eosinophilic enteritis observed during alpha-interferon therapy for chronic
      hepatitis C.
AB  - We report a patient with chronic hepatitis C who developed eosinophilic enteritis
      while being treated with recombinant interferon alpha-2b. He had no history of
      either allergic disorders or recurring episodes of abdominal cramps, nausea, or
      diarrhea. He also had had a normal eosinophil count prior to the interferon
      treatment. After a 12-week course of interferon alpha-2b, he began to complain of
      severe abdominal pain, diarrhea, and abdominal fullness. His peripheral
      eosinophil count increased to 45% (absolute count, of 7,610/microl). Abdominal
      ultrasonography and computed tomography revealed diffuse thickness of the
      intestinal wall with gross ascites that contained numerous eosinophils. An upper
      gastrointestinal barium study with small bowel follow-through showed an edematous
      mucosal layer of the jejunum and ileum. There was a spectacular relief of the
      patient's subjective symptoms after the administration of prednisolone. Follow-up
      studies revealed resolution of the ascites and the mucosal layer edema and
      normalization of the peripheral eosinophil count. Prednisolone was tapered off,
      but the eosinophilic enteritis did not recur. As there had been no evident
      exposure to common causative factors for eosinophilic enteritis, we suggest that
      interferon alpha-2b could thus have played a role in the triggering of the
      eosinophilic enteritis.

PMID- 10905365
TI  - Recurrent hepatocellular carcinoma after spontaneous regression.
AB  - The prognosis of untreated hepatocellular carcinoma (HCC) is usually grave,
      although there have been a few case reports of spontaneous regression. Tumor
      recurrence after spontaneous regression has been rarely reported, and there have
      been no previous reports of recurrent hepatocellular carcinoma after spontaneous
      regression. Two cases of hepatocellular carcinoma that spontaneously regressed
      and subsequently recurred are presented. The patients' tumors spontaneously
      regressed, as reflected by the radiologically evidenced reduction in tumor size
      and markedly decreased alpha-fetoprotein levels. Subsequent tumor recurrences
      after regression were evidenced by radiologic findings of newly growing nodules
      and appreciably increased alpha-fetoprotein levels. To the authors' knowledge,
      these two patients represent the first reported cases of hepatocellular carcinoma
      recurrence after spontaneous regression. In both of these patients, new
      hepatocellular carcinomas recurred at different sites before the spontaneous
      regression of the original HCCs was complete. Although the precise causes of the
      regression and the subsequent recurrence remain to be further investigated, this
      phenomenon suggests that multicentric hepatocarcinogenicity and intratumoral
      events in each hepatocellular carcinoma nodule may be involved.

PMID- 10905366
TI  - Multiple hepatic adenomas caused by long-term administration of androgenic
      steroids for aplastic anemia in association with familial adenomatous polyposis.
AB  - We report a rare case of hepatic adenomas (HA), in a 20-year-old Japanese girl
      treated for 6 years with anabolic androgens for aplastic anemia. In a review of
      the world literature using computer MEDLINE search, we found only 17 cases of
      androgen-induced HA published between 1975 and 1998 in the English-language
      literature. The patient was referred to us because of liver lesions detected
      during a follow-up examination for familial adenomatous polyposis. After being
      diagnosed with aplastic anemia at 14 years of age, she had been treated with
      oxymetholone (30 mg/day) for 6 years. Laboratory evaluation revealed normal liver
      function. Ultrasonography (US) and computed tomography (CT) demonstrated multiple
      liver lesions. Histopathological examinations of biopsied specimens from the
      liver tumor showed HA. After the patient was diagnosed with HA, oxymetholone was
      tapered off. Patients taking androgenic-anabolic steroids should be carefully
      monitored with US and CT and tumor markers should be measured. This report may be
      helpful in identifying the population who is at risk of developing hepatic sex
      hormone-related tumors.

PMID- 10905367
TI  - Specific detection of epstein-barr virus in inflammatory pseudotumor of the
      spleen in a patient with a high serum level of soluble IL-2 receptor.
AB  - A case of inflammatory pseudotumor of the spleen is described in a 63-year-old
      woman who presented with an intrasplenic tumor and an elevated serum level of
      soluble interleukin 2 receptor (sIL-2R). Microscopic examination after removal of
      the spleen revealed that the tumor was composed of mixed cellular infiltrates,
      mainly lymphocytes and plasma cells, and spindle-cell proliferation. Epstein-Barr
      virus (EBV) was specifically detected in the tumor by in situ hybridization for
      EBV RNA. The serum level of sIL-2R level was normalized after splenectomy. EBV
      infection may play a role in the development of splenic inflammatory pseudotumor
      and the elevation of sIL-2R level.

PMID- 10905368
TI  - Involvement of oxidative stress in the pathogenesis of NSAID-induced gastric
      mucosal damage.

PMID- 10905369
TI  - Is papillary serous carcinoma of the peritoneum (PSCP) a multifocal disease?

PMID- 10905370
TI  - Genetic regulation of the embryology of the pituitary gland and somatotrophs.
AB  - Extrinsic and intrinsic signaling gradients determine expression patterns of
      pituitary-specific factors in the developing anterior pituitary gland. The
      temporal and spatial relations of these developmental factors are required for
      the determination of each of the pituitary cell lineages. Rpx is required for
      early differentiation of the anterior pituitary. The determination of the
      somatotroph cell line is dependent on the transcription factors Lhx3, Prop-1, and
      Pit-1. Pit-1 also plays a role in the activation and regulation of the
      somatotroph gene product, GH. Additional factors such as CREB and the GHRH
      receptor, may be involved in somatotroph determination, while Zn-15 and Pitx2 may
      be involved in GH gene activation.

PMID- 10905373
TI  - Regulation and clinical assessment of growth hormone secretion.

PMID- 10905371
TI  - Physiology and disorders of the growth hormone receptor (GHR) and GH-GHR signal
      transduction.
AB  - GH exerts its actions through binding with two receptor molecules at the cell
      surface and interaction with Janus kinase and signal transducers and activators
      of transcription, and other likely effectors to stimulate metabolic effects and
      IGF synthesis. The circulating GH binding protein is the proteolytic product of
      the cell surface receptor and serves as a marker of receptor number and function.
      Thirty-six distinct mutations of the receptor in the extracellular and
      transmembrane domains cause a clinical picture of severe GH/IGF-I deficiency,
      whereas two dominant negative mutations of the intracellular domain result in a
      milder clinical syndrome. These mutations have provided insight into the
      physiology of the GH receptor. A few patients have been described with what
      appears to be primary GH insensitivity due to defective signal transduction by
      the GH-GH-receptor complex. Clinical and biochemical features of primary GH
      insensitivity are not a function of genotype, with as much variability in a
      genetically homogeneous population as in a heterogeneous one. Except for those
      dominant negative mutations where co-transfection of the mutant GH receptor gene
      with wild-type receptor gene has been informative, evidence for an effect of a
      single mutant allele remains speculative. Treatment of GH receptor deficiency
      with recombinant human IGF-I suggests that the absence of a direct effect of GH
      limits growth response.

PMID- 10905374
TI  - Gastrointestinal effects of growth hormone.
AB  - GH receptor immunoreactivity is found throughout the gastrointestinal tract. GH
      has proliferative effects upon intestinal epithelium, and influences
      enteroendocrine cell secretion, calcium absorption, and intestinal amino acid and
      ion transport. The proliferative effects of GH may be reflected in the increased
      incidence of neoplastic colonic polyps in individuals with long-term GH excess
      reported by some investigators. GH also increases hepatic cytochrome P450
      expression, potentially altering drug and steroid hormone metabolism. Current
      clinical research efforts include the use of exogenous GH as a stimulant of gut
      growth and adaptation in patients who have undergone massive intestinal
      resection. Exogenous GH is also being studied in animal models of critical
      illness where it appears to increase intestinal glutamine uptake, which may
      prevent deterioration of the intestinal mucosal barrier.

PMID- 10905372
TI  - Genetics, chemistry, and function of the IGF/IGFBP system.

PMID- 10905376
TI  - Effects of growth hormone on body composition and bone metabolism.
AB  - Physiologic effects of growth hormone (GH) extend beyond the stimulation of
      linear growth during childhood and adolescence. These effects include building
      and sustaining lean body mass, facilitating the utilization of fat mass for
      energy needs, and maintaining bone mineral density. These nongrowth effects of GH
      appear to be important throughout life. Children and adults with severe GHD
      demonstrate marked reductions in lean body mass, increases in percent body fat,
      and subnormal bone mineral density. Replacement of GH attenuates these
      abnormalities, though it remains unknown whether it does so completely. Children
      with body composition abnormalities resembling the GHD state (e.g., Prader-Willi
      syndrome) also appear to respond favorably to administration of GH treatment, and
      demonstrate concomitant improvements in strength and agility. Long-term body
      composition benefits of GH supplementation in these and other non-GHD individuals
      remain unproven.

PMID- 10905377
TI  - Growth hormone therapy in childhood-onset growth hormone deficiency: adult
      anthropometric and psychological outcomes.
AB  - The current adult heights of hypopituitary children treated with recombinant
      human growth hormone (rGH) now range between -1.5 and -0.7 height standard
      deviations (Ht SDS) of control populations. These height outcomes are markedly
      better than the ones observed following treatment with pituitary-derived human
      growth hormone (pGH) (between -4.7 and -2.0 Ht SDS). Although treatment with rGH
      has not yielded adult heights that are equal to genetic target heights, the
      discrepancy is much less now than in previous decades. Higher rGH dose, longer
      duration of treatment, early age at diagnosis, correction of height deficit prior
      to onset of puberty, and daily rGH injections have had beneficial effects on
      final adult heights. The current dosing regimens (0.3-0.18 mg/kg/wk) have not had
      an adverse effect on bone maturation and have not stimulated an earlier onset of
      puberty. Although height gains in puberty are less than controls, a majority of
      treated subjects reach heights within the normal range for adults. Higher doses
      of rGH during puberty have been studied in limited numbers of adolescents with
      positive effects; however, standard dosing will likely continue to be used
      because of financial considerations and safety concerns. Further improvements in
      adult heights are likely to be reported when the youngest children who began rGH
      in 1985 complete their growth. Several studies have investigated the quality of
      life (QOL) of GH-deficient (GHD) patients who, as children, had been treated with
      GH predominantly during the pGH era. Domains of functioning assessed include
      educational attainment, employment, and marital status. Although some studies
      have reported a generally positive adaptation, others have shown this group to
      exhibit marked deficits. Limited adult height outcomes in the pGH era of GH
      therapy has sometimes been used to account for poor outcomes. Variable behavioral
      findings are likely related to sample heterogeneity and disparate research
      methodologies and designs, most particularly the choice of control or comparison
      groups. In addition to summarizing this older literature, we report on a recently
      completed investigation in which the QOL adjustment of GHD patients is compared
      to that of same-sex siblings. Comparisons between GHD cases and norms for
      standardized questionnaires indicated both better and worse functioning in
      several domains. In contrast, very limited differences were detected between GHD
      cases and same-sex siblings. IGHD (isolated growth hormone deficiency) patients
      were functioning better than those with MPHD (multiple pituitary hormone
      deficiencies), but the effect sizes of these differences in most areas were
      relatively small. Adult height and degree of growth over the course of GH therapy
      were generally unrelated to QOL outcomes. Findings from the present study
      underscore the importance of selecting unbiased control/comparison groups in
      evaluating psychological outcomes among GHD adults.

PMID- 10905378
TI  - Value of growth hormone treatment in Turner's syndrome.

PMID- 10905375
TI  - Cardiovascular effects of growth hormone.

PMID- 10905380
TI  - Growth hormone and aging.
AB  - Aging is associated with a significant decline in secretion of growth hormone.
      This in turn leads to reduced circulating IGF-I and changes in IGF-binding
      proteins. Growth hormone replacement to growth hormone-deficient individuals has
      been shown to improve quality of life, enhance bone and muscle mass, and reduce
      cardiovascular risk. However, studies with growth hormone therapy in the elderly
      have been somewhat disappointing with minimal changes in lean body mass,
      musculoskeletal function, and overall quality of life. Moreover, recent evidence
      suggests that high normal serum IGF-I levels may be associated with a greater
      risk of several neoplastic disorders. Hence, there is less enthusiasm for
      reversing the changes of the "somatopause" with recombinant growth factors. An
      overview of these issues and the prospects for the future will be discussed in
      this article.

PMID- 10905379
TI  - Diagnosis and management of adult growth hormone deficiency.

PMID- 10905381
TI  - The "muscle-bone unit" in children and adolescents: a 2000 overview.
AB  - In former views hormones, calcium, vitamin D and other humoral and nonmechanical
      agents dominated control of postnatal bone strength (and "mass") in children and
      adolescents. However later evidence that led to the Utah paradigm of skeletal
      physiology revealed that this control depends strongly on the largest mechanical
      loads on bones. Trauma excepted, muscles cause the largest loads and the largest
      bone strains, and these strains help to control the biological mechanisms that
      determine whole-bone strength. That makes the strength of children's load-bearing
      bones depend strongly on growing muscle strength and how bones respond to it.
      Most hormones and other nonmechanical agents that affect bone strength can help
      or hinder that "bone strength-muscle strength" relationship but cannot replace
      it. In addition some agents long thought to exert bone effects by acting directly
      on bone cells, affect muscle strength too. In that way they could affect bone
      strength indirectly. Such agents include growth hormone, adrenalcorticosteroid
      analogs, androgens, calcium, genes, vitamin D and its metabolites, etc. Thus bone
      and muscle do form a kind of operational unit. It is part of the Utah paradigm
      that supplements earlier views with later evidence and concepts. The paradigm
      explains how the "bone strength-muscle strength" relationship works. This article
      provides an overview of that physiology, and some of its implications for
      pediatric endocrinologists.

PMID- 10905382
TI  - Evaluation of radial bone mineral content in prepubertal children with
      constitutional delay of growth.
AB  - We have previously reported that children with constitutionally delayed growth
      (CDG) have significantly lower spinal bone mineralization than children with
      familial short stature (FSS). The aim of the present study was to evaluate
      whether the decreased bone mineralization in children with CDG also affects the
      radius, which has a lower bone turnover than the spine. To avoid the possibility
      of size-related artifacts in the assessment of bone mineral data, data were
      corrected for bone and body size. Radial bone mineral content (RBMC) and radial
      bone mineral density (RBMD) were measured by dual energy X-ray absorptiometry
      (Hologic QDR 1000/w) in 56 short prepubertal children aged 5-11 years. All
      children had height below the 10th percentile for chronological age (CA), and
      bone age (BA) less than 10 years, 29 of them with clinical diagnosis of CDG and
      27 of them with FSS. The mean (+/- SD) RBMD was significantly lower in the
      children with CDG than in the FSS group (0.361 +/- 0.035 vs 0.385 +/- 0.033
      g/cm2, p<0.05). RBMC was significantly lower in CDG than in FSS, when multiple
      regression analysis was performed by using radial scanned bone area (RSBA), body
      weight and height, sex and BA as independent variables (p = 0.03). These data
      indicate that the decreased bone mineralization in children with CDG also affects
      peripheral bone, and that this finding is not due to bone or body size artifacts.

PMID- 10905383
TI  - Vitamin D receptor genotype and bone mineral density in Caucasian children with
      congenital hypothyroidism.
AB  - Recent studies in adults suggest that some of the genetic effects on bone mineral
      density (BMD) and bone turnover are related to allelic variation in the vitamin D
      receptor (VDR) genes. It has also been suggested in patients with hyperthyroidism
      that the VDR genotype might influence the risk of low BMD. We examined allelic
      influences of the VDR gene on BMD and metabolism in 42 children with congenital
      hypothyroidism (CH) aged 8.5 +/- 3.4 yr treated from the neonatal period and in
      whom we have previously demonstrated no detrimental effects to the skeleton of
      prolonged L-thyroxine therapy. The prevalence of the different VDR BsmI
      polymorphism in this population was as expected for Caucasian children (Bb
      heterozygote 52%, bb homozygote 31% and BB homozygote 17%). No relationship was
      found between VDR genotypes and BMD (SDS), nor between VDR genotypes and serum
      osteocalcin levels as markers of bone formation. However, urinary D-pyridinoline
      levels, as markers of bone resorption, were related to VDR genotypes (p<0.04).
      These data indicate that the VRD genotype does have some effect on bone
      metabolism in children with CH but the present results give no clear indication
      of a detrimental effect for any given VDR genotype, at least at the BsmI
      restriction site, on the bone mineralization of children with CH when adequately
      treated with thyroxine.

PMID- 10905384
TI  - Evaluation of the tubular and interstitial functions of the testis in 46,XY
      patients with ambiguous genitalia.
AB  - Investigation of the origin of sexual ambiguity is complex. Although testicular
      function has traditionally been assessed only by examining the steroidogenic
      capacity of Leydig cells and spermatogenesis, it has recently been shown that the
      measurement of serum anti-Mullerian hormone (AMH) as a marker of Sertoli cell
      function may also help clinicians. The aim of this study was to evaluate both
      Leydig and Sertoli cell functions in 46,XY patients with intersex states in order
      to establish biochemical patterns that would help to reach an etiologic
      diagnosis. We measured serum androgens, AMH and gonadotropins in 24 patients with
      sexual ambiguity and XY karyotype: 8 with gonadal dysgenesis (GD), 3 with 3beta
      hydroxysteroid dehydrogenase deficiency (3betaHSD), 5 with androgen insensitivity
      syndrome (AIS), 4 with 5alpha-reductase 2 (SRD5A2) deficiency, and 4 were of
      unknown origin or idiopathic. Our results showed that while testosterone was low
      and gonadotropins elevated in patients with either GD or 3betaHSD, AMH was low in
      the former and high in the latter. Serum AMH and gonadotropins were normal or
      high in patients with 3betaHSD or AIS, but these could be distinguished by
      testosterone levels. Serum testosterone and gonadotropins were normal or high in
      AIS and SRD5A2 deficiency patients; however, while AMH was elevated in AIS, it
      was not the case in SRD5A2 deficiency patients, indicating that testosterone is
      sufficient to inhibit AMH within the testis. In idiopathic cases gonadotropins
      and testosterone were normal, and AMH was normal or low. We conclude that the
      combined measurement of androgens, AMH and gonadotropins helps to establish the
      diagnosis in intersex patients.

PMID- 10905386
TI  - Effect of exercise training on erythrocyte insulin-like growth factor-I receptor
      binding in adolescent males.
AB  - Exercise training leads to tissue anabolism by acting through the growth hormone
      (GH)-insulin-like growth factor-I (IGF-I) axis, but the role of tissue IGF-I
      receptors in this process is not known. Erythrocyte IGF-I receptor binding is
      known to be affected by circulating levels of IGF-I. We hypothesized that
      training would lead to alterations in erythrocyte IGF-I binding. Thirty-eight
      adolescent males (mean age 16+/-0.7 yr) were randomized to a control (n=18) or
      endurance training intervention lasting 5 weeks. Erythrocyte IGF-I binding was
      measured by standard techniques. Quantity of receptor binding sites (R), binding
      affinity constant (Kaff), and nonspecific binding (NS) were calculated. Training
      led to increases (p<0.05) in 1) Kaff x R - an index of overall binding capacity
      (control, 7.3 +/-8.0%; trained, 60+/-21%); and 2) NS (control, 1.5+/-6.6%;
      trained 23.2+/-7.5%). Kaff, R, and R/erythrocyte increased in trained subjects,
      but not significantly so. These results suggest a training-associated
      upregulation of IGF-I binding. Finally, the unexpected increase in NS may reflect
      IGF binding protein activity, rather than changes in the erythrocyte IGF-I
      receptors themselves.

PMID- 10905385
TI  - Risk factors for microalbuminuria in children and adolescents with type 1
      diabetes.
AB  - OBJECTIVES: The aim of this study was to investigate the influence of sex, age,
      diabetes duration, puberty, blood pressure, glycemic control and parental blood
      pressure on microalbuminuria in children with type 1 diabetes. STUDY DESIGN: The
      study was a multicenter cross-sectional survey including 702 children and
      adolescents (age = 14.3+/-2.9 yr) with type 1 diabetes duration of 7.6+/-3.1 yr.
      One third of the population had not undergone pubertal development. Blood
      pressure was measured in children and their parents using a Dinamap instrument.
      Microalbuminuria was defined as a urinary albumin excretion rate > or = 15
      microg/min measured on at least two out of three urine collections. HbA1c
      centrally measured by HPLC, was 8.7+/-1.5%. RESULTS: The proportion of permanent
      microalbuminuria was 5.1+/-1.6%. The prevalence was significantly enhanced after
      10 yr of diabetes duration (11.6+/-5.2%) and complete puberty (8.2+/-3.1%).
      Independent risk factors for microalbuminuria tested in a logistic regression
      model were diabetes duration (OR/1 yr = 1.04-1.32), complete puberty (OR = 5.02
      8.0), and maternal hypertension (OR = 1.94-4.28). HbA1c had a borderline
      independent and significant effect (OR/1% = 0.96-1.62; p = 0.07). CONCLUSIONS:
      Our results indicate that pubertal adolescents with a long duration of the
      disease and maternal history of hypertension are candidates for targeted
      interventions with the objective of reducing the rate of developing nephropathy
      in these individuals.

PMID- 10905387
TI  - Posterior pituitary ectopy in children with idiopathic growth hormone deficiency.
AB  - AIMS: To evaluate the underlying pathogenesis in children with pituitary hormone
      deficiency by means of high resolution MRI of the brain. PATIENTS/METHODS: Thirty
      seven children with short stature and isolated GH deficiency (IGHD, n = 17) or
      multiple pituitary hormone deficiency (MPHD, n = 20) were subjected to an MRI of
      the brain at the age of 1.0-17.3 years. The anatomic condition of the hypothalamo
      pituitary area was analyzed and the height of the pituitary gland was measured
      and compared to the data of age-matched healthy subjects. RESULTS: Seventy
      percent of the patients had a characteristic anomaly: the adenohypophysis was
      hypoplastic, the infundibulum was absent and the posterior pituitary lobe was
      ectopic at the bottom of the median eminence. The height of the anterior
      pituitary was significantly reduced in these patients (1.9 +/- 0.1 mm; mean +/-
      SD) when compared to age-matched healthy controls (4.1 +/- 0.8 mm, p<0.001) or
      hypopituitary patients with a normal MRI (4.3 +/- 0.8 mm). MPHD was found in 62%
      of patients with the pituitary anomaly whereas only 27% of children with a normal
      MRI had MPHD (p<0.05). CONCLUSIONS: The pathogenesis of the pituitary anomaly is
      unknown; a disorder during embryonal development or perinatal events have been
      discussed as causal factors. MRI should have a prominent position in the work-up
      of hypopituitary children. When an anatomical malformation is visualized by MRI,
      the diagnostic terminology should be adapted accordingly.

PMID- 10905388
TI  - Comparison between four immunoassays for growth hormone (GH) measurement as
      guides to clinical decisions following GH provocative tests.
AB  - OBJECTIVE: To compare four assays for the measurement of GH following provocative
      tests and to assess the projected clinical decisions, which would have been based
      on their respective results. DESIGN: Multiple assays of serum samples obtained
      during provocative tests for GH response. SUBJECTS: Forty-seven children with
      short stature, who underwent clinical evaluation and GH provocative tests.
      METHODS: All samples were measured by the immunoassay Sorin-RIA (A), which is
      routinely used in our laboratory. Basal and peak samples were analyzed by three
      other immunoassays: Sorin-IRMA (B), DPC-RIA (C) and Wallac-DELFIA (D). Results
      were classified as low, partial and normal GH response, corresponding to <10, 10
      17.9 and >18 microIU/ml peak serum GH levels. RESULTS: High correlation was found
      between individual results by the four kits (r=0.92-0.94). However, the mean peak
      GH values were significantly different (p<0.0001). Further analysis using paired
      t-test has shown highly significant differences between the assays (p<0.0001)
      apart from assays A and B that were not significantly different. Clinical
      grouping by the four tests was profoundly different: by assay A, 14.9% were
      judged low response and 57.4% normal; by assay D, 36.2% were low and only 21.3%
      normal. Kappa statistics measurement demonstrated poor agreement between assays A
      and D and between B and D. CONCLUSION: As the criteria for the diagnosis of GH
      deficiency and the indications for GH therapy are based on laboratory GH results,
      more must be done to ensure uniformity and comparability of the GH assays.

PMID- 10905389
TI  - Growth during and after a trial of growth hormone releasing hormone 1-29 in
      children with idiopathic short stature or growth hormone neurosecretory
      dysfunction.
AB  - The growth promoting effects of once nightly subcutaneous injections of growth
      hormone releasing hormone (GHRH) 1-29 (30 microg/kg) for 6 months were studied in
      16 slowly growing prepubertal children with idiopathic short stature (ISS; Group
      1) and 8 similar children with growth hormone neurosecretory dysfunction (GHND;
      Group 2). Each child underwent endogenous growth hormone evaluation using both
      pharmacological and physiological testing; each had stimulated values > 10
      microg/l and were subsequently placed into one of two groups based on pooled 12
      hour overnight GH of < or > or = 3 microg/l. Each patient was followed every
      three months for one year. There were no significant differences in the two
      groups throughout the study with the exception of the endogenous GH levels. Both
      groups responded to GHRH therapy with similar significant increases in their
      rates of growth. Although a subset of patients (6 of 21) continued to grow at a
      rate significantly greater than the pre-therapy rate of growth, overall rates of
      growth were not significantly different from the pre-therapy growth rates 6
      months following the discontinuation of GHRH treatment. We conclude that GHRH 1
      29, given in the doses provided, leads to similar changes in growth rates in
      short, slowly growing children who are GH sufficient and those with GHND. Despite
      prior reports to the contrary, GHND patients do not experience a sustained
      increased in growth rate upon discontinuation of GHRH.

PMID- 10905390
TI  - Early onset of endocrine abnormalities in beta-thalassemia major in a developing
      country.
AB  - Endocrine complications in patients with thalassemia major in developing
      countries may be frequent due to suboptimal iron chelation. Data from developing
      countries are scant. We prospectively evaluated growth, growth hormone (GH),
      insulin-like growth factor I, thyroid hormone, cortisol and glucose tolerance in
      84 patients over one year. Height standard deviation (SD) score of patients > 8
      years (-2.2 +/- 1.5 against National Center for Health Statistics references) was
      significantly lower than that of normal controls (-1.0 +/- 0.7, p < 0.001). 51%
      of patients had GH deficiency, 13% hypocortisolism and 7.9% diabetes/impaired
      glucose tolerance. Ten of 11 adolescents/young adults had hypogonadism. Of 54
      preadolescent children who underwent dynamic testing, 18 (33%) had at least one
      endocrine deficiency other than short stature. We conclude that hypogonadism and
      hypocortisolism form important causes for morbidity in our thalassemic children.
      Thalassemic patients in developing countries may be at risk for endocrine
      deficiencies at younger ages.

PMID- 10905391
TI  - Post-surgical metabolic imbalance in adolescents with renal hypophosphatemic
      rickets.

PMID- 10905392
TI  - Transient congenital hypoparathyroidism and 22q11 deletion.
AB  - CATCH-22 syndrome represents a spectrum of abnormalities associated with
      microdeletions of chromosome 22q11. We report a patient with transient congenital
      hypoparathyroidism, with severe neonatal hypocalcemia and spontaneous resolution
      in infancy, tetralogy of Fallot and thymic hypoplasia. Genetic confirmation of
      chromosome 22q11 deletion was made. Newborns with congenital hypoparathyroidism
      need genetic analysis and examination for anomalies associated with CATCH-22
      syndrome.

PMID- 10905393
TI  - Bilateral ovarian steroid cell tumor in congenital adrenal hyperplasia due to
      classic 11beta-hydroxylase deficiency.
AB  - An 8.7 year-old patient, raised as a boy, presented with premature appearance of
      pubic hair and accelerated growth since 2 years of age and ambiguous genitalia
      noted at birth. There was first degree consanguinity between his parents. A
      similar problem was reported in a cousin. Examination of the external genitalia
      revealed complete scrotal fusion, a 5 cm long phallus, urogenital sinus at base
      of phallus with no gonads palpable. Pigmentation was increased. His blood
      pressure was 150/100 mm Hg. Pubic and axillary hair were at stage 3. Bone age was
      17 years. Adrenal ultrasound was normal. Pelvic ultrasound showed relatively
      enlarged uterus and ovaries with normal echogenicity. Karyotype was 46,XX.
      Hormone profile was compatible with congenital adrenal hyperplasia (CAH) due to
      11beta-hydroxylase deficiency (11-deoxycortisol: 11.5 nmol/l [400 ng/dl] [normal:
      0.6-4.5 nmol/l [20-155 ng/ml]], androstenedione: 17.4 nmol/l [5 ng/ml] [normal:
      0.1-1.2 nmol/l [0.03-0.35 ng/ml]]). Prednisolone and antihypertensive drugs were
      started. The patient underwent bilateral salpingo-oophorectomy and hysterectomy
      at 9.1 years. Histopathological examination of both ovaries revealed steroid cell
      tumor. The type of the tumor was "not otherwise specified" (NOS). Basal hormone
      levels and ACTH test performed 10 months after the operation and 7 days off
      treatment reconfirmed the diagnosis of 11beta-hydroxylase deficiency. Steroid
      cell tumors are extremely rare forms of steroid hormone-reducing ovarian
      neoplasms in childhood and may coexist with or imitate virilizing CAH.

PMID- 10905394
TI  - Glucose-6-phosphate dehydrogenase deficiency-induced hemolysis in newly diagnosed
      diabetic monozygotic twins.
AB  - A pair of monozygotic male twins are described who manifested hemolysis at the
      concurrent onset of diabetes type 1. Hemolysis appeared progressively following
      the correction of hyperglycemia and ketoacidosis (one twin). It was found to be
      related to unknown glucose 6-phosphate dehydrogenase (G-6-PD) deficiency. Other
      causes of hemolysis such as drugs or bacterial infection were excluded. The fall
      in glucose availability after the correction of hyperglycemia is proposed as a
      possible explanation for hemolysis.

PMID- 10905395
TI  - Cyclophosphamide and water retention: mechanism revisited.
AB  - We describe an 8 year-old girl with established diabetes insipidus who developed
      cyclophosphamide-associated antidiuresis. The patient had received
      cyclophosphamide as part of a high-dose chemotherapy regimen for recurrent
      suprasellar dysgerminoma prior to autologous bone marrow transplantation. Urinary
      output decreased and specific gravity increased shortly after a 1 hour i.v.
      infusion of 50 mg/kg cyclophosphamide and the effect lasted some 5 hours. No
      other drug could be implicated. This response, occurring in a patient with no
      ability to secrete vasopressin, suggests a direct tubular effect of one or more
      cyclophosphamide metabolites. Administering i.v. cyclophosphamide requires
      careful monitoring of fluid balance in order to avoid water intoxication. Further
      research is warranted both into the mechanism of this effect and the metabolite
      responsible for it.

PMID- 10905396
TI  - Treatment with deferiprone (L1) in a thalassemic patient with bone lesions due to
      desferrioxamine.
AB  - A male thalassemia major patient who developed bone and cartilage abnormalities
      with a standard dose of desferrioxamine (DFX) given subcutaneously from the age
      of 4 years was treated with the oral iron chelator deferiprone (L1). During L1
      treatment an improvement of genu valgum, evidence of healing and filling in of
      bone at the periphery of knee metaphysis and improvement in growth velocity were
      observed. However, the sitting height had decreased further, confirming the
      irreversibility of platyspondylosis, so affecting the near final standing height
      (156.8 cm) which was below the mid-parental height (168 cm). Prospective studies
      are warranted to determine the effect of different iron chelators on the bone
      metabolism of patients with thalassemia.

PMID- 10905397
TI  - Resonant frequency pattern in multifrequency tympanograms: results in normally
      hearing subjects.
AB  - This paper presents experimental data on the evaluation of middle ear resonances
      by multifrequency tympanometry. Multifrequency tympanograms (MFTs) of 18 normally
      hearing subjects were recorded with a frequency resolution of 15 Hz. The fine
      structure found in the MFT patterns was compared with findings in literature. A
      first approach for the evaluation of this fine structure was made explaining the
      great variability of the main ossicular resonance frequencies described in
      previous publications. The consequence of the present investigation is that the
      concept of the main ossicular resonance has to be revised critically.

PMID- 10905399
TI  - Long-term audiometric follow-up of click-evoked auditory brainstem response in
      hearing-impaired infants.
AB  - Conventional pure-tone thresholds were collected as determined at ages between 4
      and 8 years from a group of 163 infants, tested by auditory brainstem response
      (ABR) in the age range between 1 and 3 years old for objective hearing
      assessment. The subjects suffered from a variety of degrees and types of
      sensorineural hearing impairment. The prognostic value of the ABR peak V
      thresholds in response to 0.1 ms clicks with respect to the behavioural
      thresholds at octave frequencies from 125 to 8,000 Hz obtained later is
      evaluated. Correlation between ABR and behavioural thresholds is largest in the
      1,000- to 8,000-Hz frequency range. Predicted pure-tone audiograms (mean and SD)
      were determined for each 10-dB class of ABR thresholds. SDs are in the order of
      15 to 18 dB in the 500- to 4,000-Hz range and slightly higher at adjacent
      frequencies (i.e., somewhat larger than in comparable adult studies). Mean pure
      tone thresholds in the 1,000- to 8,000-Hz frequency range are up to 20 dB worse
      than ABR thresholds, which is opposite to findings in normally-hearing subjects.
      Thus, with an increasing degree of sensorineural hearing impairment, pure-tone
      thresholds increase at a significantly higher rate than ABR thresholds. The
      observation is explained in terms of reduced temporal integration in cochlear
      hearing loss. ABR thresholds worse than 80 dB nHL are demonstrated to have very
      limited predictive value with respect to the amount of residual hearing, not only
      in the low- but also in the high-frequency range. The presence of otitis media
      during ABR testing is shown to make estimation errors increase to more than 25 dB
      (SD).

PMID- 10905398
TI  - Transient-evoked otoacoustic emissions in a representative population sample aged
      18 to 25 years.
AB  - Transient-evoked otoacoustic emissions (TEOAEs) were obtained from 688 ears of a
      group of 345 young adults aged 18 to 25 years, using the Otodynamics ILO88 in the
      standard, non-linear mode. Normative data for TEOAEs obtained from 186
      otologically normal (ON) ears are presented. In 5 ON ears, there was no
      recordable response, despite hearing threshold levels better than 20 dB. The main
      factors affecting the TEOAE level were (1) gender, where females had larger
      responses on average than males; (2) tympanometric measures, where ears with
      entirely normal tympanometric measures had larger responses than those with minor
      tympanometric abnormalities; (3) click stimulus intensity measured in the ear
      canal, which correlated positively with TEOAE level; and (4) hearing threshold
      level at 0.5 kHz, which correlated negatively with amplitude. There was also a
      small effect of social noise exposure in the 2-kHz region of the TEOAE, where the
      response was lower in those subjects exposed to significant social noise.

PMID- 10905400
TI  - Objective intraoperative method to record averaged electromyographic stapedius
      muscle reflexes in cochlear implant patients.
AB  - We have developed a procedure to measure the averaged stapedius muscle reflex in
      response to electrical stimulation (AESR) with a cochlear implant. The AESR, as
      activated by ipsilateral stimulation with a cochlear implant, was investigated
      intra-operatively in a series of 12 children. After the cochlear implant was
      placed into the cochlea and secured by the surgeon, an electromyographic (EMG)
      needle electrode was gently placed into the stapedius muscle. During stimulation
      of the cochlear implant, the stapedius reflex was monitored visually (VESR) and
      as an averaged EMG response (AESR). Consistent AESRs were obtained in 7 of the 12
      children. These measures provide a method to obtain stapedius muscle responses
      that may be helpful in the programming of young children with cochlear implants.
      Comparative post-operative measures were also obtained, including behavioral
      threshold levels, behavioral comfort levels, and the contralateral stapedius
      reflex threshold (ESR) on selected electrodes.

PMID- 10905401
TI  - Tonotopic mapping in auditory cortex of the adult chinchilla with amikacin
      induced cochlear lesions.
AB  - We have found a reorganization of tonotopic maps (based on neuron response
      thresholds) in primary auditory cortex of the adult chinchilla after amikacin
      induced basal cochlear lesions. We find an over-representation of a frequency
      that corresponds to the border area of the cochlear lesion. The reorganization
      observed is similar in extent to that previously seen in a developmental model.
      The properties of neurons within the over-represented area were investigated in
      order to determine whether their responses originated from a common input (an
      indication of true plasticity) or represented only the result of truncating the
      activity of the sensory epithelium ("pseudo-plasticity"). Some aspects of our
      data fit with a true plasticity model and indicate the potential for the
      deafferented cortex of the mature cortex to regain connections with the surviving
      sensory epithelium.

PMID- 10905402
TI  - Toward a clinical procedure for narrowband gap detection I: a psychophysical
      procedure.
AB  - This paper examines a possible procedure for a clinical gap-detection test that
      is simple, frequency specific, and reliable. A cued yes-no method of maximum
      likelihood (MML) procedure was compared to an up-down three-interval, two
      alternative, forced-choice procedure. Results from five trained and seven naive
      listeners indicate that the yes-no MML procedure yields valid and efficient
      estimates of narrowband gap-detection thresholds. Preliminary tests yield
      encouraging results.

PMID- 10905403
TI  - Central auditory processing disorder as the presenting manifestation of subtle
      brain pathology.
AB  - The objective of this case-report study was to assess the presence of central
      auditory impairment in a patient with a normal neurological examination. This
      subject was a 45-year-old female with gradually deteriorating hearing
      difficulties over a period of 5 years and a borderline normal audiogram.
      Behavioural central auditory tests were used, including Dichotic Sentence
      Identification Test, Competing Sentences Test, and auditory event-related
      potentials (mismatch negativity). Behavioural central auditory tests and mismatch
      negativity results were abnormal and indicated disordered central auditory
      processing. Subsequent magnetic resonance imaging of the brain identified subtle
      changes consistent with small-vessel ischaemic disease. Adult patients who
      present with hearing difficulties that cannot be explained on the basis of their
      audiogram should undergo central auditory assessment, as the auditory symptoms
      may be the first and only manifestation of central nervous system pathology.

PMID- 10905404
TI  - Synthesis of carbonated calcium phosphate ceramics using microwave irradiation.
AB  - Carbonated hydroxyapatites (CHA) were synthesized by the substitution of calcium
      carbonate for calcium hydroxide during the reaction with diammonium phosphate
      under microwave irradiation. The X-ray powder diffraction analysis indicates the
      decrease of alpha-axis up to 20 mol% of carbonate substitution confirming the
      formation of the B-type CHA. Further increase of carbonate content shows the
      presence of tricalcium phosphate (TCP) in addition to CHA. Reaction of
      substituted magnesium carbonate instead of calcium carbonate in the above process
      results in the formation of biphasic calcium phosphate (BCP) ceramics consisting
      of both CHA and TCP phases. Fourier transform infrared spectroscopic study also
      confirmed the carbonate substitution in HA and BCP formation. The in vitro
      solubility study in phosphate buffer of pH 7.2 at 37 degrees C showed the
      resorbable nature of the BCP samples. The present study thus indicates the
      feasibility of in situ formation of BCP ceramics using microwave irradiation.

PMID- 10905405
TI  - Vinylpyrrolidone-N,N'-dimethylacrylamide water-soluble copolymers: synthesis,
      physical-chemical properties and proteic interactions.
AB  - The radical copolymerization of N-vinyl-2-pyrrolidone (NVP) with N,N'
      dimethylacrylamide (DMAm) has been studied. The copolymer compositions were
      determined from 1H-NMR. The radical reactivity ratios for DMAm (M1) and VP (M2)
      were found to be r1 = 2.232 and r2 = 0.186. An analysis of the water vapor
      absorption isotherms as a function of the lactam content in the copolymer is
      reported. It was observed that the water vapor absorption decreases with
      increasing VP content in the copolymer and show anomalous diffusion behavior with
      increasing temperature due to the coupling of diffusion and polymer relaxation
      mechanisms. From the water vapor sorption data the Arrhenius activation parameter
      (ED) and enthalpy of sorption (deltaH S) were determined. The activation
      parameters are found to follow the conventional trend. The poly(DMAm-co-VP)
      copolymers exhibited a decreased critical solution temperature (LCST) in
      proportion to their lactam content. Contact angle data were evaluated for the
      determination of surface free energy components (gamma d SV, gamma P SV and gamma
      SV) of the synthesized polymers. The dispersion force component (gamma d SV) of
      copolymers increased only slightly with the VP content whereas the polar force
      component (gamma P SV) decreased with the lactam content. No dependence was
      observed between the surface free energy (gamma SV) and copolymer compositions.
      The complex formation between bovine serum albumin (BSA) and the VP-DMAm
      copolymers in water was studied by fluorescence spectroscopy. It was found that
      the copolymers bind to BSA non-specifically on the surface. Phase separation was
      not observed after addition of copolymers to BSA solutions at pH higher or lower
      than isoelectric point of BSA.

PMID- 10905406
TI  - Chemical and physicochemical characterization of porous hydroxyapatite ceramics
      made of natural bone.
AB  - The properties of a porous hydroxyapatite ceramic produced by sintering of bovine
      bone were investigated by using a number of physicochemical methods such as
      scanning electron microscopy (SEM), SEM in combination with energy dispersive X
      ray spectroscopy (SEM-EDX), mercury intrusion porosimetry, krypton-adsorption,
      contact angle measurements, wide angle X-ray diffraction. Fourier transform
      infrared spectroscopy, thermal analysis, inductively coupled plasma optical atom
      emissions spectroscopy and flame atomic absorption spectroscopy. The results
      indicate that there are considerable differences between the ceramic and native
      bone. However, the most important properties with respect to the use of such
      ceramics as a biomaterial for filling bone defects namely the high porosity (> or
      = 57 +/- 2%) and the interconnecting pore system are maintained. While macropores
      with an average diameter of approx. 300 microm contribute 97% to porosity,
      micropores with an average diameter of 1.3 microm account for only 3% of the
      total porosity. The surface area was found to be approx. 0.1 m2/g. The contact
      angles of water (44.6 +/- 15.4 degrees, n = 5) and tetrahydrofurane (10 degrees)
      allow the processing of the ceramic to a drug carrier by incubation with aqueous
      or organic drug solutions. The ceramic is highly crystalline with crystal sizes
      of 1-7 microm and contains crystal bridges. The investigation of its chemical
      composition revealed small amounts of other inorganic compounds such as
      Ca4O(PO4)2, NaCaPO4, Ca3(PO4)2, CaO, and MgO. Besides trace amounts of aluminum,
      iron, magnesium, potassium, silica, sodium, vanadium and zinc it contains
      probably carbonated apatite.

PMID- 10905407
TI  - Influence of particle size and dissolution conditions on the degradation
      properties of polylactide-co-glycolide particles.
AB  - Polymer degradation usually plays a crucial role in drug release from sustained
      release polyester systems, therefore in order to elucidate the mechanism
      governing release, it appears essential to analyse the in vitro degradation
      behaviour of these devices. In this study the influence of processing conditions,
      particle characteristics and release media temperature on the degradation of PLGA
      spherical particles were examined. It was found that a linear relationship
      between the degradation rate and particle size existed, with the larger particles
      degrading fastest. In smaller particles degradation products formed within the
      particle can diffuse easily to the surface while in larger particles degradation
      products have a longer path to the surface of the particle during which
      autocatalytic degradation of the remaining polymer material can occur. The
      influence of release media temperature on the degradation of PLGA particles was
      also examined. At lower incubation temperatures PLGA microparticles showed an
      induction period after which polymer degradation proceeded. The rate of polymer
      degradation was found to increase with increasing incubation temperature. The
      polymer erosion profile was fitted to the Prout-Tompkins equation and the rate
      constants were used to determine the activation energy of PLGA hydrolysis.

PMID- 10905408
TI  - The effect of nitrogen diffusion hardening on the surface chemistry and scratch
      resistance of Ti-6A1-4V alloy.
AB  - Modular, head-stem, mixed-metal connections are susceptible to mechanically
      mediated electrochemical interactions. Any attempt to improve the performance of
      these connections should center around increasing their resistance to mechanical
      damage, particularly the titanium alloy (Ti64). This study investigated the
      effect of a nitrogen-diffusion-hardening process on Ti64, with specific reference
      to changes in composition, chemistry, electrochemistry and its ability to resist
      and/or repassivate scratch damage. The nitrogen-diffusion-hardened Ti64 alloy had
      TiN and TiNO complexes at the immediate surface and sub-surface layers. The
      diffusion-hardened samples also had a deeper penetration of oxygen compared to
      regular Ti64 alloy samples. The electrochemical impedance spectroscopy data
      corroborated the increased thickness of the barrier oxide on the diffusion
      hardened samples. The nitrogen-diffusion-hardened samples were more resistant to
      scratch damage and repaired/repassivated faster after such damage. The results
      suggest that the nitrogen-diffusion-hardened titanium alloy should exhibit
      increased resistance to mechanical-electrochemical interactions in mixed-metal
      modular interfaces in total hip prostheses.

PMID- 10905409
TI  - Characterization of glucose-sensitive insulin release systems in simulated in
      vivo conditions.
AB  - We studied the glucose-responsive insulin controlled release system based on the
      hydrogel poly(2-hydroxyethyl methacrylate-co-N,N-dimethylaminoethyl
      methacrylate), also called poly(HEMA-co-DMAEMA), with entrapped glucose oxidase,
      catalase and insulin. When exposed to physiological fluids, glucose diffuses into
      the hydrogel, glucose oxidase catalyzes the glucose conversion to gluconic acid,
      causing swelling of the pH-sensitive hydrogel and subsequently increased insulin
      release. The higher the glucose concentration in the medium, the higher and
      faster the swelling and release rates. The effects of polymer morphology and
      oxygen availability on hydrogel swelling and on insulin release kinetics were
      tested. Polymer morphology was modified by changing the crosslinking agent
      (tetraethylene glycol dimethacrylate) concentration (0-0.95 vol%). Oxygen
      availability was modified by changing the immobilized catalase concentration (0
      15 units catalase per unit glucose oxidase) and by bubbling oxygen through the
      medium. The results indicated that: (i) Hydrogels without crosslinking agent were
      found to be stable in water, and their sensitivity to pH and glucose was higher
      than the chemically crosslinked hydrogels. (ii) Immobilization of catalase in
      addition to glucose oxidase in hydrogels prepared without crosslinking agent,
      resulted in enhanced swelling kinetic. In addition, we carried out primary in
      vivo experiments on rats, which demonstrated that at least some of the entrapped
      insulin retains its active form and is effective in reducing blood glucose
      levels. Moreover, no tissue encapsulation was observed around matrices implanted
      in the peritoneum. In conclusion, the pH-sensitive hydrogel poly(HEMA-co-DMAEMA)
      can be manipulated to produce glucose-responsive insulin release system that is
      effective in reducing blood glucose levels.

PMID- 10905410
TI  - Attachment of glycosaminoglycans to collagenous matrices modulates the tissue
      response in rats.
AB  - Biocompatibility and tissue regenerating capacity are essential characteristics
      in the design of collagenous biomaterials for tissue engineering. Attachment of
      glycosaminoglycans (GAGs) to collagen may add to these characteristics by
      creating an appropriate micro-environment. In this study, porous type I collagen
      matrices were crosslinked using 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide,
      in the presence and absence of chondroitin sulfate and heparan sulfate. The
      tissue response to these matrices was evaluated after subcutaneous implantation
      in rats. Biocompatibility of the matrices was established by the induction of a
      transitional inflammatory response, and the generation of new host tissue. Non
      crosslinked collagen was gradually resorbed and replaced by collagenous
      connective tissue. By contrast, crosslinked matrices, with and without GAGs.
      retained their scaffold integrity during implantation, and supported the
      interstitial deposition and organization of extracellular matrix. In addition,
      crosslinking decreased tissue reactions at late time intervals. No calcification
      in any of the implants was observed. The presence of GAGs preserved porous
      lamellar matrix structures. Heparan sulfate in particular promoted angiogenesis
      at weeks 2 and 4, predominantly at the matrix periphery. The almost complete
      absence of macrophages and giant cells associated with collagen-GAG matrices,
      after 10 weeks implantation, indicated a reduced foreign body reaction. It is
      concluded that attachment of GAGs to collagen matrices modulates the tissue
      response. The potential of these biocompatible scaffolds for tissue engineering
      is increased by preserving porous matrix integrity. promoting angiogenesis and
      reducing foreign body reactions.

PMID- 10905411
TI  - Characterization of plasma proteins adsorbed onto biomaterials. By MALDI-TOFMS.
AB  - The analysis of plasma proteins adsorbed onto a polyurethane (PU) biomaterial was
      performed using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS). This article marks the first study on MALDI-TOFMS
      analysis of multiple proteins adsorbed from plasma, in vitro, onto the surface of
      a biomaterial to easily enable their characterization. Plasma standards from
      three different hosts were placed in contact with non-porous PU, a model
      biomaterial. Following the use of washing protocols developed in our laboratory,
      the biomaterial was analyzed, directly, with MALDI-TOFMS. Proteins with molecular
      weights (Mr) ranging from ca. 6.5 to 150 kDa were observed in the mass spectra
      and characterized upon comparison with proteins of known Mr. The proteins
      observed were tentatively identified as those known to adsorb onto PU, both in
      vitro and in vivo. In an attempt to model in vivo sorption, the PU biomaterial
      was exposed to freshly collected canine plasma, in vitro, for different lengths
      of time. Corresponding MALDI-TOFMS spectra displayed increasing protein signal
      for a number of different proteins with increasing times of exposure to plasma.
      This method provided qualitative and semi-quantitative analysis of the proteins
      adsorbed onto the biomaterial surface.

PMID- 10905412
TI  - Tooth slice organ culture for cytotoxicity assessment of dental materials.
AB  - The purpose of this work was to develop a tooth slice organ culture method to
      assess the response of the cells of the dental pulp to commonly used dental
      materials and products. Wistar rat tooth slices were grown in culture for two and
      ten days in the presence of dental materials. After culture, the tooth tissues
      were processed and the responses of the pulpal cells were analysed
      histomorphometrically. Cytotoxic cell destruction was observed following the
      direct application of test materials to tooth slices (n = 298) after 10 days in
      culture (MANOVA, P = 0.0001), whilst the restoration of prepared deep dentine
      cavities (n = 30), with test products, did not result in a significant amount of
      pulpal injury (MANOVA, P = 0.287). In rank order of causing pulpal injury, the
      test materials from the most to the least cell destructive, was; Salicylic acid.
      Calcium hydroxide, Kalzinol zinc oxide eugenol, high-mercury Amalgam, Prime &
      Bond, Dycal, Barium sulphate, Hypocal, Scotchbond, Calasept, Life and One-step.
      Tooth slice organ culture, provided a cytotoxicity screening method for dental
      materials, bearing a closer physiological resemblance to the clinical situation
      than cell culture screening methods. Tooth slice culturing may have the potential
      to replace some types of in vivo animal experimentation, as there is a clear need
      to reduce this form of testing.

PMID- 10905414
TI  - Social support, attachment, and psychopathology in high risk formerly maltreated
      adults.
AB  - OBJECTIVE: The aim of this study was to examine the relationships among social
      support, attachment security, and psychopathology in an adult sample of high risk
      abuse survivors. Attachment security was conceptualized in terms of two
      underlying dimensions, the working models of self and other. METHOD: Sixty-six
      participants (24 men and 42 women) who met conditions for physical or sexual
      abuse were recruited from the greater Boston area. They completed the "Record of
      Maltreatment Experiences." the "Relationship Scales Questionnaire," the "Norbeck
      Social Support Questionnaire," and multiple measures of psychopathology. RESULTS:
      When multiple risk and protective factors were examined concurrently (e.g.,
      social support, attachment, abuse history, IQ, SES), a negative view of self (one
      of the attachment poles) was the strongest predictor of overall psychopathology.
      Social support did not emerge as a significant direct predictor of
      psychopathology, once the effects of negative view of self were accounted for.
      However, among participants low on social support, in comparison to those who are
      high, a negative view of self was more highly correlated with some
      psychopathology measures. CONCLUSIONS: These findings indicate that among
      maltreatment survivors, negative view of self emerges as the most substantial
      predictor of psychopathology when examined in combination with other relevant
      risk factors.

PMID- 10905413
TI  - Persistence of bullying from childhood to adolescence--a longitudinal 8-year
      follow-up study.
AB  - OBJECTIVE: To examine factors associated with bullying and victimization from age
      8 to 16. METHOD: An 8-year longitudinal study included questions about bullying
      and victimization at age 8 and 16. Children were evaluated with Rutter scales by
      parents and teachers and with the Child Depression Inventory filled in by the
      children at age 8. When the children were at the age of 16 parents filled in the
      CBCL and adolescents the YSR. RESULTS: About 15% of boys and 7% of girls were
      bullied and 12% of girls and 13% of boys were victimized at age 16. Both bullying
      and victimization at age 16 were associated with a wide range of psychological
      problems at age 8 and 16, and with referral to child mental health services.
      Bullying at age 8 was associated with bullying at age 16, while victimization at
      age 8 was associated with victimization 8 years later. CONCLUSIONS: Bullying and
      victimization are often persistent and associated with severe emotional and
      behavior problems. Preventive efforts should be focused, and targeted at those
      children who are characterized by both psychological disturbance and bullying.

PMID- 10905415
TI  - Opinions among mandated reporters toward child maltreatment reporting policies.
AB  - OBJECTIVE: This study investigates the opinions of social workers, pediatricians,
      and physician assistants in their support for the existing child maltreatment
      mandated reporting policy and an alternative reporting policy. Differences in
      professional training, age, gender, reporting behavior, attitudes towards
      reporting, and level of certainty needed to report were considered in determining
      which group of mandated reporters was most likely to support either the existing
      or an alternative policy. METHOD: A total of 382 social workers, pediatricians,
      and physician assistants in Connecticut and Massachusetts completed a self-report
      questionnaire. This sample represented an overall adjusted response rate of 76%.
      RESULTS: There was slightly more support for the existing reporting policy
      compared to the alternative policy. After controlling for age, attitudinal
      variables, and reporting behavior, social workers were significantly more likely
      to favor an alternative child maltreatment reporting policy than pediatricians or
      physician assistants. Also, those mandated reporters who had not consistently
      reported all suspected cases of maltreatment were significantly more likely to
      favor the alternative policy than consistent reporters. CONCLUSIONS: Because the
      majority of mandated reporters do not consistently report all suspected cases of
      maltreatment and support for an alternative reporting policy varies among
      different groups, consideration of alternative strategies and policies that
      address the concerns of different types of professionals may be appropriate.

PMID- 10905416
TI  - [Study of the consequences of physical neglect on the psychological development
      of preschool children in Spain].

PMID- 10905417
TI  - Drug-exposed infant cases in juvenile court: risk factors and court outcomes.
AB  - OBJECTIVE: The purpose of this study was to determine which factors were
      significantly associated with court outcomes for drug exposed infants in
      dependency court. METHOD: A longitudinal study of 118 drug exposed infant social
      services and juvenile court files of petitioned cases through all court hearings,
      using chi-squares and logistic regressions data analysis. RESULTS: There was an
      overrepresentation of minority mothers who were poor, unemployed, undereducated,
      and single, with prior referrals to the dependency system and criminal records.
      The chi-square analysis suggested that variables such as ethnicity, past
      referrals, and criminal record were significantly associated with court outcomes
      for all hearings, with minority cases less likely to receive family maintenance
      orders, and more likely to have their children placed out of home. The regression
      analysis however showed a different pattern. Ethnicity and prior referrals
      disappeared as significant risk factors altogether. Only at the initial
      dispositional hearing did a criminal record significantly influence court
      decisions. In subsequent hearings, mothers' compliance with court orders and
      attending court hearings became the significant factors associated with court
      outcomes. CONCLUSIONS: Mothers' behavior was more important for court outcomes
      than ethnicity, past referrals, and criminal record. It is therefore imperative
      that mothers are motivated to successfully comply with court orders by offering
      culturally appropriate services and facilitating attendance at court hearings.

PMID- 10905418
TI  - Perinatal complications and child abuse in a poverty sample.
AB  - OBJECTIVE: Perinatal medical illness has been associated with child maltreatment.
      Using a Child Protective Service (CPS) report as the defining event, this study
      explores to what extent perinatal morbidity is a risk factor for maltreatment.
      METHOD: Medical charts of 206 children ages 0-3 years were reviewed. Data
      regarding birth history were collected and analyzed in three groups of children:
      children whose medical record indicated a report to CPS based on prenatal
      findings (Early Maternal Inadequacy group [EMI]), children whose medical record
      indicated a report to CPS based only on postnatal findings (Child Maltreatment
      group [CM]), and a control group without CPS report (NM). RESULTS: Compared to
      the CM and the NM groups, children in the EMI group showed significantly lower
      birth weight and higher neonatal morbidity as measured by Apgar scores, frequency
      of oxygen requirement and intubation at birth, frequency of admission to Neonatal
      Intensive Care unit, and frequency of neonatal medical problems. There was no
      significant difference between the CM and the NM groups in birth weight,
      gestational age, and other measures of morbidity. CONCLUSION: The results of the
      study suggest that perinatal complications are associated with prenatal
      maltreatment. Previously reported strong associations between neonatal morbidity
      and child abuse are more likely a result of antecedent prenatal maternal
      behaviors (early maternal inadequacy). Early maternal inadequacy, a clinically
      and demographically distinct phenomenon, is important due to serious health,
      development and financial implications and deserves further exploration.

PMID- 10905419
TI  - Sexual abuse characteristics associated with survivor psychopathology.
AB  - OBJECTIVE: This study was designed to examine predictors of psychopathology in
      non-clinically referred, sexually abused (SA) children, ages 6-16 years, 30-60
      days following abuse disclosure and termination. METHOD: Eighty SA children were
      administered a structured diagnostic interview and a variety of rating-scale
      instruments. Several forms of psychopathology were assessed, including
      posttraumatic stress, global functioning, anxiety, depression, and externalizing
      behavior. Abuse interviews also were used to guide the collection of demographic
      (victim age, gender) and abuse-related information (e.g., frequency of abuse).
      RESULTS: Abuse-related factors and demographic variables accounted for greater
      than half of the variance predicting global functioning, and accurately predicted
      posttraumatic stress disorder (PTSD) status for 86% of the participants. Also,
      analyses yielded significant predictors of parent-reported attention problems and
      sexual behavior. Of additional importance, none of the abuse-related and
      demographic variables predicted scores on measures of general anxiety,
      depression, and externalizing behavior. CONCLUSIONS: Specific demographic and
      sexual abuse information may, to some extent, be used to identify children who
      are at increased risk for short-term post-abuse psychopathology. Although the
      present findings suggest that such information may not be useful in the
      prediction of general anxiety, depression, and externalizing behavior,
      demographic and abuse-related variables importantly appear to account for
      significant variance in the prediction of global functioning, posttraumatic
      stress, attentiveness, and sexual behavior. Additional research is needed to
      improve mental health professionals' ability to identify SA children who are at
      high risk for psychopathology.

PMID- 10905420
TI  - Adolescent sexual offender recidivism: success of specialized treatment and
      implications for risk prediction.
AB  - OBJECTIVE: To evaluate the success of specialized community-based treatment for
      reducing adolescent sexual reoffending and explore the predictive utility of
      variables assessed regarding sexual and nonsexual recidivism. METHOD: Recidivism
      data (criminal charges) were collected for 58 offenders participating in at least
      12 months of specialized treatment at the SAFE-T Program. Data were also
      collected for a comparison group of 90 adolescents who received only an
      assessment (n = 46), refused treatment (n = 17), or dropped out before 12 months
      (n = 27). Follow-up interval ranged from 2 to 10 years (M = 6.23, SD = 2.02).
      Offenders completed a battery of psychological tests to provide standardized data
      regarding social, sexual, and family functioning. RESULTS: Recidivism rates for
      sexual, violent nonsexual, and nonviolent offenses for treated adolescents were
      5.17%, 18.9%, and 20.7%, respectively. The Comparison group had significantly
      higher rates of sexual (17.8%), violent nonsexual (32.2%), and nonviolent (50%)
      recidivism. Sexual recidivism was predicted by sexual interest in children.
      Nonsexual recidivism was related to factors commonly predictive of general
      delinquency such as history of previous offenses, low self-esteem, and antisocial
      personality. CONCLUSIONS: Results support the efficacy of treatment for
      adolescent sexual offenders and are consistent with the notion that sexual
      recidivism is predicted by unique factors unrelated to general (nonsexual)
      reoffending.

PMID- 10905421
TI  - Predictors of treatment outcome in sexually abused children.
AB  - PROBLEM: This study evaluated the impact of child and family characteristics on
      treatment outcome of sexually abused children. METHOD: Forty-nine recently
      sexually abused 7- to 14-year-old children were randomly assigned to either abuse
      focused cognitive behavioral therapy or nondirective supportive therapy, and
      assessed pre- and post-treatment using several standardized instruments. These
      included five measures of psychological symptomatology and four measures of child
      and family characteristics hypothesized to mediate treatment response.
      Correlational and multiple regression analyses were utilized to evaluate the
      impact of the following mediating factors on treatment outcome: Children's abuse
      related attributions and perceptions; family cohesion and adaptability; parental
      support of the child; and parental emotional reaction to the child's abuse.
      RESULTS: Children's abuse-related attributions and perceptions and parental
      support of the child were strong predictors of treatment outcome in this
      population. CONCLUSIONS: Therapeutic attention to children's sexual abuse-related
      attributions and to enhancing parental support may be important factors in
      optimizing treatment outcome in 8- to 14-year-old sexually abused children.

PMID- 10905422
TI  - "Children don't do sex with adults for pleasure": Sri Lankan children's views on
      sex and sexual exploitation.
AB  - OBJECTIVE: A pilot study to ascertain the prevalence, attitudes and practice of
      sexual behavior in young adolescent school children at risk of sexual
      exploitation in Sri Lanka. To find out children's perceptions of how children can
      be helped not to be sexually abused and to help those who have already been
      exploited. METHOD: An anonymous self completed questionnaire with 145 school
      children aged 13 to 17 years. Four schools were deliberately selected in high
      risk beach areas. RESULTS: Ten percent of children said they had done sexual
      things, 8% with other children their age, 5% with adults, and 6% with adults for
      money (8% of children did not respond to this question). Most children felt it
      was not acceptable for children to do sexual things with adults. Children
      appeared to be strongly against the damage they felt it could do to children and
      their communities. Only a small proportion of children said they learnt about sex
      from school (12%) or their parents (10%). They had a number of misconceptions on
      AIDS and although a third had received teaching nearly half said they wanted
      teaching on it. Children had creative ideas on intervention but much of it
      focused on what adults could do to address the root causes of inadequate care of
      children. Children also felt that adults should be punished which contrasts with
      the police attitude which has been criticized for putting the blame on the child
      rather than the adult. CONCLUSIONS: As recipients of sexual exploitation,
      children have insights into the problem and are able to give information that can
      be used in policy and planning of preventive, sex education and rehabilitation
      programs addressing sexual exploitation.

PMID- 10905423
TI  - Two deaths, one blind eye, one imprisonment: child abuse in the guise of corporal
      punishment in Nigerian schools.
AB  - An examination of reported cases of child abuse in Nigerian schools was carried
      out against the backdrop of the legal framework for the protection of pupils. The
      objective was to highlight the deficiency in Nigerian law on child protection in
      the light of UN Conventions which Nigeria has ratified.

PMID- 10905424
TI  - Characterization of trans-splicing in Euglenoids.
AB  - We have looked for trans-splicing of nuclear mRNAs in several Euglenoid species.
      In Cyclidiopsis acus, Phacus curvicauda, Rhabdomonas costata and Menoidium
      pellucidum we showed that several premRNAs chosen at random are matured by a
      transsplicing process: we identified SL-RNA genes whose 5' ends (SLs for spliced
      leader-sequences) were transferred to the 5' extremities of mRNAs. The SL-RNA
      genes are located on repeated DNA fragments which also encode 5S rRNA in P.
      curvicauda and C. acus. The potential secondary structures of SL-RNAs are
      compared to those previously characterized in two other Euglenoids: Euglena
      gracilis and Entosiphon sulcatum. In another Euglenoid species, Distigma proteus,
      since none of the mRNAs examined were trans-spliced, it is possible that trans
      splicing does not occur. Phylogeny based on 5S rRNA sequences suggests that the
      species which have, or have had, chloroplasts (E. gracilis, P. curvicauda, C.
      acus) diverged early from the others.

PMID- 10905425
TI  - Phosphorylation is required for high-affinity binding of DBP, a yeast
      mitochondrial site-specific RNA binding protein.
AB  - All yeast mitochondrial mRNAs terminate at their 3' ends with a conserved
      dodecamer sequence, a site for high-affinity binding by DBP (dodecamer binding
      protein). Using purified DBP, we show that binding requires an intact dodecamer
      site and is enhanced by the presence in an oligonucleotide of the immediate 4-5
      upstream nucleotides. Binding affinity varied from 0.25 to 0.85 nM towards a set
      of RNA oligonucleotides containing messenger specific upstream sequences in
      addition to the dodecamer site. Furthermore, we show that phosphatase treatment
      of DBP abolishes its specific binding, indicating the involvement of reversible
      phosphorylation in the regulation of its binding activities. This finding will
      further our understanding of the mechanism of DBP in the regulation of RNA
      metabolism in yeast mitochondria.

PMID- 10905426
TI  - A novel 'two-component' protein containing histidine kinase and response
      regulator domains required for sporulation in Aspergillus nidulans.
AB  - We have characterised a-novel Aspergillus nidulans gene encoding a 'two
      component' signalling protein (tcsA). tcsA encodes both a histidine kinase domain
      and a response regulator domain similar to those found in bacterial, lower
      eukaryotic and plant members of the two-component family of proteins, while two
      PAS domains in the amino-terminal region of the predicted tcsA product may
      monitor the signal which regulates a tcsA histidine kinase-response regulator
      phosphorelay. While tcsA is nonessential for vegetative growth, cells lacking the
      gene are unable to produce conidia on standard Aspergillus growth media. However,
      tcsA is not absolutely required for production since this defect is suppressed by
      growth on 1 M sorbitol.

PMID- 10905427
TI  - Identification of functional elements that regulate the glucoamylase-encoding
      gene (glaB) expressed in solid-state culture of Aspergillus oryzae.
AB  - Aspergillus oryzae has-two glucoamylase-encoding genes, glaA and glaB, whose
      expressions are distinguished by the type of culture used. The glaB gene is
      markedly expressed in solid-state culture but is little expressed in submerged
      culture. In solid-state culture, glaB expression at the transcriptional level is
      enhanced by low-Aw (water activity), high-temperature, and physical barriers to
      hyphal extension, as well as by starch. To determine the cis-acting factors in
      the glaB promoter, deletion analysis of the promoter was done with GUS (beta
      glucuronidase) as the reporter. Deletion of the 27 bp from -350 to -324 (Region
      A) in 1.1 kb of the glaB promoter completely abolished starch, low-Aw, and high
      temperature induction. Substitution of the 12-bp GC-rich motif from -335 to -324
      (GC-box) resulted in significant loss of starch and low-Aw inductivities. These
      findings suggest that the GC-box is a cis-element essential for the high-level
      expression of glaB in solid-state culture.

PMID- 10905428
TI  - An Aspergillus oryzae CCAAT-binding protein, AoCP, is involved in the high-level
      expression of the Taka-amylase A gene.
AB  - Aspergillus oryzae contains a nuclear protein designated AoCP, which binds
      specifically to a CCAAT sequence in the promoter region of the A. oryzae Taka
      amylase A gene. A gene encoding a homologue of Aspergillus nidulans HAPC, a
      subunit of the A. nidulans CCAAT binding complex, was isolated from A. oryzae and
      designated AohapC. AoHAPC comprises 215 amino acids and shows 84% identity to A.
      nidulans HAPC. Transformation of the A. nidulans hapC deletion strain with the
      AohapC gene restored the CCAAT binding activity, resulting in both enhancement of
      taa gene expression and complementation for the poor growth phenotype of this
      strain. Furthermore, introduction of the AohapC gene also restored the expression
      of the A. nidulans eglA gene, encoding an endo-beta-1,4-glucanase, in the
      deletion strain. These results indicate functional interchangeability of the
      genes from two species.

PMID- 10905429
TI  - Glucose dependent transcriptional expression of the cre1 gene in Acremonium
      chrysogenum strains showing different levels of cephalosporin C production.
AB  - The cre1 gene from the beta-lactam producer Acremonium chrysogenum has been
      isolated and characterized in order to study glucose-dependent gene expression in
      this biotechnically important fungus. The deduced protein sequence is highly
      similar to amino-acid sequences of other known glucose repressors from
      filamentous fungi, and carries conserved zinc-finger and regulatory motifs.
      Contrary to cre gene expression in Trichoderma reesei and Aspergillus nidulans,
      the transcript level of the cre1 gene from an A. chrysogenum wild-type strain is
      increased in the presence of glucose. Remarkably, the glucose-dependent
      transcriptional upregulation does not take place in another A. chysogenum strain,
      which displays enhanced production of the beta-lactam antibiotic cephalosporin C.
      We surmise that the de-regulation of cre1 is connected with the increased
      production rate in this strain.

PMID- 10905430
TI  - Carbon source regulation of a dextranase gene from the filamentous fungus
      Penicillium minioluteum.
AB  - The regulation of dextranase (dexA) gene expression in the filamentous fungus
      Penicillium minioluteum grown on different carbon sources was studied. Growth in
      the presence of dextran leads to high expression of the dextranase enzyme, but
      growth in starch, glucose, glycerol, lactose and sorbitol did not. Dextran
      induced dexA gene expression at the mRNA level. However, in cultures containing
      dextran plus glucose or glycerol, the transcript was detected 24 h later than in
      the case where dextran was the only carbon source. When the glucose or glycerol
      concentration in the dextran-containing medium was kept at about 1% (w/v), no
      dextranase-transcripts were detected. It was found that both glucose and glycerol
      inhibited enzyme synthesis, because 1% (w/v) addition of both carbon sources to
      dextran-growing cultures was able to abolish the inducing effect of dextran. Our
      results suggest that dextran utilization responds to both specific induction and
      to glucose and glycerol repression, providing evidence that P. minioluteum dexA
      expression is regulated by the carbon source at the transcriptional level.

PMID- 10905431
TI  - Two pheromone precursor genes are transcriptionally expressed in the homothallic
      ascomycete Sordaria macrospora.
AB  - In order to analyze the involvement of pheromones in cell recognition and mating
      in a homothallic fungus, two putative pheromone precursor genes, named ppg1 and
      ppg2, were isolated from a genomic library of Sordaria macrospora. The ppg1 gene
      is predicted to encode a precursor pheromone that is processed by a Kex2-like
      protease to yield a pheromone that is structurally similar to the alpha-factor of
      the yeast Saccharomyces cerevisiae. The ppg2 gene encodes a 24-amino-acid
      polypeptide that contains a putative farnesylated and carboxy methylated C
      terminal cysteine residue. The sequences of the predicted pheromones display
      strong structural similarity to those encoded by putative pheromones of
      heterothallic filamentous ascomycetes. Both genes are expressed during the life
      cycle of S. macrospora. This is the first description of pheromone precursor
      genes encoded by a homothallic fungus. Southern-hybridization experiments
      indicated that ppg1 and ppg2 homologues are also present in other homothallic
      ascomycetes.

PMID- 10905432
TI  - The ribosomal DNA of the Zygomycete Mucor miehei.
AB  - The ribosomal DNA-from the Zygomycete Mucor miehei has been characterised. The
      complete rDNA unit was cloned by heterologous PCR using primers whose sequence
      matched conserved regions of the rDNA from related fungal species. The sequence
      of the overlapping PCR products revealed the existence of a repeated unit of 9574
      bp. The genes encoding the different rRNA species were identified by their
      homology to the corresponding sequences from other fungi. We estimate that the
      rDNA unit is present in the genome of M. miehei in about 100 copies. This
      estimation was made by comparing the intensity of its hybridisation signal in a
      Southern blot with that of the mmp gene coding for aspartyl protease, which was
      assumed to be contained in single copy. The size and structure of the M. miehei
      rDNA unit was similar to that of other fungi. The genes encoding the 25S, 18S and
      5.8S RNAs are closely linked within the repeated unit which also contains the 5S
      gene. This latter gene appears to be transcribed in the opposite direction. The
      25S, 18S and 5.8S genes showed 70-80% homology to the corresponding genes from
      other fungi, whereas the degree of homology for the 5S gene was much lower. The
      highest homology (about 80%) corresponded to the few available sequences from
      other Mucor species. Homology to genes from other Zygomycota was no higher than
      that observed for genes from the Ascomycota or Basidiomycota fungi.

PMID- 10905433
TI  - The aetiology of idiopathic scoliosis: biomechanical and neuromuscular factors.
AB  - The aetiology of idiopathic scoliosis: biomechanical and neuromuscular factors
      small curve develops due to a small defect in the neuromuscular control system
      and a second stage during adolescent growth in which the scoliotic curve is
      exacerbated by biomechanical factors.

PMID- 10905434
TI  - Optimization method for 3D bracing correction of scoliosis using a finite element
      model.
AB  - Scoliosis is a complex three-dimensional deformity of the spine and rib cage
      frequently treated by brace. Although bracing produces significant correction in
      the frontal plane, it generally reduces the normal sagittal plane curvatures and
      has limited effect in the transverse plane. The goal of this study is to develop
      a new optimization approach using a finite element model of the spine and rib
      cage in order to find optimal correction patterns. The objective function to be
      minimized took account of coronal and sagittal offsets from a normal spine at the
      thoracic and lumbar apices as well as the rib hump. Two different optimization
      studies were performed using the finite element model, which was personalized to
      the geometry of 20 different scoliotic patients. The first study took into
      account only the thoracic deformity, while the second considered both the
      thoracic and lumbar deformities. The optimization produced an average of 56% and
      51% reduction of the objective function respectively in the two studies. Optimal
      forces were mostly located on the convex side of the curve. This study
      demonstrates the feasibility of using an optimization approach with a finite
      element model of the trunk to analyze the biomechanics of bracing, and may be
      useful in the design of new and more effective braces.

PMID- 10905435
TI  - Segmental pedicle screw instrumentation in idiopathic thoracolumbar and lumbar
      scoliosis.
AB  - The role of posterior correction and fusion in thoracolumbar and lumbar scoliosis
      as well as pedicle screw instrumentation in scoliosis surgery are matters of
      debate. Our hypothesis was that in lumbar and thoracolumbar scoliosis, segmental
      pedicle screw instrumentation is safe and enables a good frontal and sagittal
      plane correction with a fusion length comparable to anterior instrumentation. In
      a prospective clinical trial, 12 consecutive patients with idiopathic
      thoracolumbar or lumbar scolioses of between 40 degrees and 60 degrees Cobb angle
      underwent segmental pedicle screw instrumentation. Minimum follow-up was 4 years
      (range 48-60 months). Fusion length was defined according to the rules for Zielke
      instrumentation, normally ranging between the end vertebrae of the major curve.
      Radiometric analysis included coronal and sagittal plane correction.
      Additionally, the accuracy of pedicle screw placement was measured by use of
      postoperative computed tomographic scans. Major curve correction averaged 64.6%,
      with a loss of correction of 3 degrees. The tilt angle was corrected by 67.0%,
      the compensatory thoracic curve corrected spontaneously according to the
      flexibility on the preoperative bending films, and led to a satisfactory frontal
      balance in all cases. Average fusion length was the same as that of the major
      curve. Pathological thoracolumbar kyphosis was completely corrected in all but
      one case. One patient required surgical revision with extension of the fusion to
      the midthoracic spine due to a painful junctional kyphosis. Eighty-five of 104
      screws were graded "within the pedicle", 10 screws had penetrated laterally, 5
      screws bilaterally and 4 screws medially. No neurological complications were
      noted. In conclusion, despite the limited number of patients, this study shows
      that segmental pedicle screw instrumentation is a safe and effective procedure in
      the surgical correction of both frontal and sagittal plane deformity in
      thoracolumbar and lumbar scoliosis of less than 60 degrees, with a short fusion
      length, comparable to anterior fusion techniques, and minimal loss of correction.

PMID- 10905436
TI  - Can hindbrain decompression for syringomyelia lead to regression of scoliosis?
AB  - Scoliosis in childhood develops secondary to syringomyelia in some children. The
      existing literature does not provide a clear answer as to whether surgical
      treatment of the syrinx can allow subsequent improvement of the spinal deformity,
      thus preventing the need for scoliosis surgery. This series comprised 16 patients
      with syringomyelia who presented with significant scoliosis in the absence of
      major neurological deficit. All underwent a hindbrain decompression, and follow
      up ranged from 1 to 6 years (mean 2.5 years). Subsequent deformity surgery was
      necessary in eight cases, but the scoliosis was seen to improve or arrest its
      progression in six (37.5%). Improvement was found to be statistically more likely
      in children of younger age at the time of syrinx surgery and in those with left
      thoracic curves. Improvement occurred in 71.4% of those under the age of 10 at
      the time of hindbrain decompression.

PMID- 10905437
TI  - Single-blind randomised controlled trial of chemonucleolysis and manipulation in
      the treatment of symptomatic lumbar disc herniation.
AB  - This single-blind randomised clinical trial compared osteopathic manipulative
      treatment with chemonucleolysis (used as a control of known efficacy) for
      symptomatic lumbar disc herniation. Forty patients with sciatica due to this
      diagnosis (confirmed by imaging) were treated either by chemonucleolysis or
      manipulation. Outcomes (leg pain, back pain and self-reported disability) were
      measured at 2 weeks, 6 weeks and 12 months. The mean values for all outcomes
      improved in both groups. By 12 months, there was no statistically significant
      difference in outcome between the treatments, but manipulation produced a
      statistically significant greater improvement for back pain and disability in the
      first few weeks. A similar number from both groups required additional
      orthopaedic intervention; there were no serious complications. Crude cost
      analysis suggested an overall financial advantage from manipulation. Because
      osteopathic manipulation produced a 12-month outcome that was equivalent to
      chemonucleolysis, it can be considered as an option for the treatment of
      symptomatic lumbar disc herniation, at least in the absence of clear indications
      for surgery. Further study into the value of manipulation at a more acute stage
      is warranted.

PMID- 10905438
TI  - The relationship of disability (Oswestry) and pain drawings to functional
      testing.
AB  - There was much enthusiasm about the development of computerized dynamometry in
      providing large quantities of data to objectively assess muscle performance.
      However, a much more basic issue arose questioning what these machines actual
      measure, particularly in pain populations. The purpose of the present study was
      to determine whether patients' self-reported disability and pain expression, as
      evaluated with simple questionnaires, were related to isokinetic performance in
      low back pain patients. METHOD: Oswestry Disability Questionnaires and pain
      drawings were collected from 76 patients undergoing isokinetic testing upon
      entering a physical rehabilitation program. Isokinetic trunk testing was
      performed in the standing position and results recorded for flexion and extension
      at speeds of 50 degrees, 100 degrees, and 150 degrees per second. RESULTS:
      Patients indicating minimal disability on the Oswestry questionnaire performed
      better than those indicating greater levels of disability (P < 0.05; ANOVA with
      Tukey adjustment for multiple comparisons). Patients with greater pain drawing
      scores, indicating unusual pain patterns, performed more poorly during isokinetic
      testing than those with normal drawings (P < 0.05). Regression analysis revealed
      that the lifting question from the Oswestry questionnaire, pain drawings scores,
      and sex were all significantly related to isokinetic performance and could
      account for 37.6-48.1% of the variance in performance (varying with speed of
      test). CONCLUSIONS: The results of this study indicate that isokinetic test
      values are significantly influenced by a patient's self-reported disability and
      pain expression, which can be evaluated using simple tools such as pain drawings
      and the Oswestry questionnaire. This study supports the supposition that
      dynamometry testing is related to factors other than muscle performance.

PMID- 10905439
TI  - Intradiscal pressure after intradiscal injection of hypertonic saline: an
      experimental study.
AB  - Although chemonucleolysis with chymopapain is a long-established treatment for
      lumbar intervertebral disc herniation, serious complications have been reported.
      Accordingly, alternative substances for chemonucleolysis have been sought. The
      main beneficial effect of chemonucleolysis derives from the decrease in
      intradiscal pressure. Several previous studies have investigated the relationship
      between physiological saline injection and disc mechanics in cadaveric specimens
      [2, 5, 16]. However, no previous study has assessed the intradiscal pressure
      after intradiscal injection of "hypertonic saline" in living animals. The present
      study compared the changes in intradiscal pressure after intradiscal injection of
      hypertonic saline with those after chymopapain injection. The lumbar
      intervertebral discs of 26 living rabbits were examined: 10% hypertonic saline
      was injected in ten rabbits, and chymopapain (10 pikokatal units) was injected
      intradiscally in another ten, with the remaining six being used as controls. The
      intradiscal pressure was measured at 1, 4, and 12 weeks after injection. The
      intradiscal pressure of the hypertonic saline-injected group at 4 weeks was
      significantly lower than that of the control group, but by 12 weeks it had
      recovered. On the other hand, that of the chymopapain-injected group remained
      significantly lower than that of the control group at 12 weeks. The results of
      this study found that hypertonic saline injected into the intervertebral discs
      temporarily decreased the intradiscal pressure.

PMID- 10905440
TI  - Relationships between epidural fibrosis, pain, disability, and psychological
      factors after lumbar disc surgery.
AB  - Failed back surgery syndrome (FBSS) is an important complication of lumbar disc
      surgery. Epidural fibrosis is one of the major causes of FBSS. However, most
      patients with epidural fibrosis do not develop symptomatic complaints from
      scarring. The purpose of this prospective study was to evaluate the relationships
      among the severity of epidural fibrosis, psychological factors, back pain and
      disability after lumbar disc surgery. Twenty-nine surgically managed patients (13
      women, 16 men) were included in this study. In all patients, the presence and
      severity of epidural fibrosis was determined with contrast-enhanced magnetic
      resonance imaging (MRI). A pain visual analog scale (VAS) and Oswestry Disability
      Questionnaire (ODQ) were completed before and after surgery. Subjects were
      grouped by their type of herniation (protrusion, free fragment), MRI findings and
      results of the mini form of the Minnesota Multiphasic Personality Inventory
      (MMPI), and the groups were compared for their VAS and ODQ scores. Our results
      disclosed that neither the postoperative VAS scores nor the postoperative ODQ
      scores differed significantly among the epidural fibrosis severity groups.
      Moreover, postoperative VAS scores were positively correlated with the scores of
      the mini MMPI. These findings indicate that epidural fibrosis may be considered
      as a radiological entity independent of patients' complaints. Furthermore, the
      mini MMPI should be included in the assessment and planning of the reoperations
      in FBSS patients, because of the importance of psychological factors in
      postoperative pain and disability.

PMID- 10905441
TI  - Anterior lumbar interbody fusion with threaded fusion cages and autologous bone
      grafts.
AB  - The goal of this study was to evaluate the ability of Ray threaded fusion cages,
      when used in an anterior approach, to restore intervertebral height and to
      improve the functional and occupational performance of the patients. The present
      study was initiated because insertion of fusion cages through a posterior
      approach causes destruction of facet joints and violation of the spinal canal.
      The anterior approach for insertion of threaded fusion cages to accomplish lumbar
      interbody fusion was evaluated in a series of 13 patients suffering monosegmental
      disc disease. The patients' functional and occupational performance was evaluated
      using the Prolo score. Radiological measurements were used to evaluate disc
      height and degree of penetration into the endplates, and to confirm fusion. Seven
      of the 13 patients were short-term failures and had to be revised within 2 years.
      The study found that revised patients had poorer Prolo scores than non-revised
      patients. Although for the non-revised patients, the mean Prolo scores remained
      relatively stable during the 1st year, they dropped after 3 years. We were not
      able to identify any further clinical or radiological differences between the
      groups. These results indicate that although the anterior approach seems
      technically suitable for insertion of threaded fusion cages, destruction of the
      anterior longitudinal ligament and the anterior part of the annulus fibrosis
      appears to result in destabilisation of the motion segment.

PMID- 10905442
TI  - A method to evaluate the in vivo behaviour of lumbar spine implants.
AB  - The aim of the study was to design a method for evaluating the stabilizing effect
      of different lumbar spine implants in vivo, and to apply this method to a
      comparison of plates versus rods in lumbar spine posterolateral fusion using
      transpedicular screw fixation. Fourteen patients, seven operated on with
      transpedicular plates and screws (VSP), and seven operated on with rods and
      screws (Diapason), matched according to number of levels fused, had tantalum
      markers inserted in the vertebrae at surgery, enabling roentgen
      stereophotogrammetric analysis (RSA). Mean patient age was 45 (range 33-56)
      years. In each group, two patients underwent fusion between L4 and L5, three
      between L5 and S1, and two from L4 to S1. In three patients, concomitant nerve
      root decompression was performed using a facet joint preserving technique. RSA
      was performed 4 weeks after surgery. This interval was chosen to allow enough
      time for soft tissue healing, but not fusion healing, to occur. RSA was performed
      in supine and standing position without any mobility provocation, in line with
      the postoperative regimen given. Movements between the outermost vertebrae of the
      fusion were calculated along the transverse, vertical and sagittal axes. The
      method of measurement along these three axes has previously been determined to be
      accurate to 0.3, 0.6 and 0.7 mm, respectively. One patient stabilized with rods
      and screws between L5 and S1 displayed a sagittal translation of 1.01 mm but no
      mobility along the transverse or vertical axes. In the remaining 13 patients,
      positional change from supine to standing did not provoke any intervertebral
      mobility above the RSA accuracy along any of the axes. With the limited
      provocation described, in line with the postoperative regimen for lumbar fusion
      patients, plates with transpedicular screws and rods with transpedicular screws
      both seem to give adequate intervertebral stability in posterolateral lumbar
      fusions.

PMID- 10905443
TI  - Accuracy of pedicle screw insertion with and without computer assistance: a
      randomised controlled clinical study in 100 consecutive patients.
AB  - We performed a randomised controlled study to assess the accuracy of computer
      assisted pedicle screw insertion versus conventional screw placement under
      clinical conditions. One hundred patients scheduled for posterior thoracolumbar
      or lumbosacral pedicle screw instrumentation were randomised into two groups,
      either for conventional pedicle screw placement or computer-assisted screw
      application using an optoelectronic navigation system. From the computer-assisted
      group, nine patients were excluded: one because of an inadequate preoperative
      computed tomography study, seven because of problems with the specific
      instruments or the computer system, and one because of an intraoperative
      anesthesiological complication. Thus, there were 50 patients in the conventional
      group and 41 in the computer-assisted group, and the number of screws inserted
      was 277 and 219, respectively. There was no statistical difference between the
      groups concerning age, gender, diagnosis, type of operation performed, mean
      operating time, blood loss, or number of screws inserted. The time taken for
      screw insertion was significantly longer in the computer-assisted group.
      Postoperatively, screw positions were assessed by an independent radiologist
      using a sophisticated CT imaging protocol. The pedicle perforation rate was 13.4%
      in the conventional group and 4.6% in the computer-assisted group (P = 0.006).
      Pedicle perforations of more than 4 mm were found in 1.4% (4/277) of the screw
      insertions in the conventional group, and none in the computer-assisted group.
      Complications not related to pedicle screws were two L5 nerve root lesions, one
      end plate fracture, one major intraoperative bleeding and one postoperative death
      in the conventional group, and one deep infection in the computer-assisted group.
      In conclusion, pedicular screws were inserted more accurately with image-guided
      computer navigation than with conventional methods.

PMID- 10905444
TI  - Geometrical dimensions of the lower lumbar vertebrae--analysis of data from
      digitised CT images.
AB  - The precise dimensions of the lumbar vertebrae and discs are critical for the
      production of appropriate spinal implants. Unfortunately, existing databases of
      vertebral and intervertebral dimensions are limited either in accuracy, study
      population or parameters recorded. The objective of this study is to provide a
      large and accurate database of lumbar spinal characteristics from 126 digitised
      computed tomographic (CT) images, reviewed using the Picture Archiving
      Communication System (PACS) coupled with its internal measuring instrumentation.
      These CT images were obtained from patients with low back pain attending the
      spinal clinic at the Hammersmith Hospitals NHS Trust. Measurements of various
      aspects of vertebral dimensions and geometry were recorded, including vertebral
      and intervertebral disc height. The results from this study indicated that the
      depth and width of the vertebral endplate increased from the third to the fifth
      lumbar vertebra. Anterior vertebral height remained the same from the third to
      the fifth vertebra, but the posterior vertebral height decreased. Mean disc
      height in the lower lumbar segments was 11.6 +/- 1.8 mm for the L3/4 disc, 11.3
      +/- 2.1 mm for the L4/5, and 10.7 +/- 2.1 mm for the L5/S1 level. The average
      circumference of the lower endplate of the fourth lumbar vertebra was 141 mm and
      the average surface area was 1,492 mm2. An increasing pedicle width from a mean
      of 9.6 +/- 2.2 mm at L3 through to 16.2 +/- 2.8 mm at L5 was noted. A
      comprehensive database of vertebral and intervertebral dimensions was generated
      from 378 lumbar vertebrae from 126 patients measured with a precise digital
      technique. These results are invaluable in establishing an anthropometric model
      of the human lumbar spine, and provide useful data for anatomical research. In
      addition this is important information for the scientific planning of spinal
      surgery and for the design of spinal implants.

PMID- 10905445
TI  - Biomechanical evaluation of the New Zealand white rabbit lumbar spine: a
      physiologic characterization.
AB  - Physiologic motions of the human, sheep, and calf lumbar spines have been well
      characterized. The size, cost, and ease of care all make the rabbit an attractive
      alternative choice for an animal lumbar spine model. However, comparisons of
      normal biomechanical characteristics of the rabbit lumbar spine have not been
      made to the spines of larger species. The purpose of this study was to establish
      baseline physiologic kinematic data for the rabbit lumbar spine. Ten skeletally
      mature New Zealand white rabbit osteoligamentous spines were obtained. L4-L7
      spine segments were harvested and mounted. Multi-directional flexibility testing
      was performed by applying pure moments up to 0.27 Nm. Resulting rotations were
      measured using an Optotrak system. Data were analyzed for each intervertebral
      level in the three planes of rotation. The three levels tested had roughly
      similar range of motion (ROM). The mean (SD) angular ROMs in flexion for L4-L5,
      L5-L6, L6-L7 were 12.10 degrees (2.59 degrees), 12.38 degrees (2.70 degrees), and
      15.17 degrees (3.22 degrees), respectively. The ROMs in extension were 5.86
      degrees (1.21 degrees), 5.58 degrees (1.48 degrees), and 6.13 degrees (2.03
      degrees). Lateral bending and axial rotation were roughly symmetric due to the
      symmetric nature of the spine. For right lateral bending, the ROMs were 8.25
      degrees (2.44 degrees), 4.96 degrees (1.70 degrees ), and 4.25 degrees (1.20
      degrees). For left axial rotation, the ROMs were 1.23 degrees (1.16 degrees),
      0.35 degrees (0.61 degrees), 0.87 degrees (0.64 degrees ). Neutral zone (NZ) was
      on average 60% (29%) of ROM for the motions studied. The physiologic ROM of the
      New Zealand white rabbit lumbar spine was found to be similar between the rabbit
      and human. This relatively conserved physiologic flexibility supports the use of
      the rabbit as a model of the lumbar spine for kinematic studies. However, the
      overall NZ was found to be a greater percentage of ROM in the rabbit than the
      corresponding percentage in the human (60% as compared to 25%). This suggested
      that the rabbit lumbar spine has a greater laxity than that of the human.

PMID- 10905446
TI  - Pain pattern in multiple vertebral hemangiomas involving non-adjacent levels:
      report of two cases.
AB  - Hemangioma of the bone is a benign tumor usually involving the spine and the
      bones of the skull and pelvis. It may be either a single lesion or part of a
      generalized multifocal disease. Multiple lesions involving non-adjacent vertebrae
      are rare. Two cases of multiple vertebral hemangiomas at non-adjacent levels with
      different pain patterns are presented at various stages of follow-up in order to
      emphasize the fact that multiple vertebral hemangiomas may present with different
      clinical characteristics over a long period of time. The change in the location
      and pattern of the initially presented pain in both patients suggested the
      possibility of multiple level involvement. Investigation revealed multiple
      hemangiomas involving three non-adjacent vertebrae in the first patient and four
      in the second. We stress the fact that the existence of multiple non-adjacent
      lesions may remain undiagnosed for a considerable period of time and may be
      responsible for even longer-term recurrent episodes of pain. Multifocal location
      of back pain in patients with a known vertebral hemangioma may be considered a
      relative indication for the presence of multiple non-adjacent level lesions.

PMID- 10905447
TI  - Preliminary neural response telemetry results.
AB  - This paper describes the neural response telemetry (NRT) results obtained from
      the first 30 patients tested at this centre. One hundred per cent of patients
      tested intra-operatively had NRT responses on at least one electrode; this
      compared to 82.4% of patients tested post-operatively. Reasonable correlations
      existed between post-operative NRT thresholds and psychophysical threshold and
      comfort levels, although there was too much variability for the data to be used
      to set these parameters directly. Post-operative NRT thresholds were always at
      levels audible to patients.

PMID- 10905448
TI  - Recognition of dichotic digits under pre-cued and post-cued response conditions
      in young and elderly listeners.
AB  - Dichotic listening was evaluated in pre-cued and post-cued response conditions
      using a hierarchical set of one-, two- and three-pair dichotic digit materials.
      Thirty young adults (mean age 29.1 years) with normal hearing, and 30 older
      adults in the 60-79-year age range (mean age 68.7 years) with mild-to-moderate
      sensorineural hearing loss were evaluated. Several patterns of performance were
      observed. First, recognition performance in the pre-cued condition was better
      than recognition performance in the post-cued condition for one-, two- and three
      pair digits for both age groups. Second, there was a right ear advantage in pre-
      and post-cued response conditions for both age groups. In the pre-cued condition,
      the right ear advantage was small owing to ceiling effects associated with ease
      of the listening task. In the post-cued condition, recognition performance
      decreased as a function of age, and left ear scores decreased faster than right
      ear scores, resulting in a larger right ear advantage in the 60-79-year group.
      Third, as the complexity of the listening task increased from easy (one-pair) to
      difficult (three-pairs), there was a corresponding decrease in recognition
      performance for both age groups. The increase in the difference in performance on
      easy and difficult tasks became larger as a function of age.

PMID- 10905449
TI  - Use of the nine-step inflation/deflation test as a predictor of middle ear
      barotrauma in sports scuba divers.
AB  - Middle ear (ME) barotrauma, the most common disorder encountered in diving,
      results from inadequate pressure equilibration between the ME and the ambient
      environment. Eustachian tube function plays a key role in the pathogenesis of
      barotrauma. This study was designed to investigate the predictive value and
      efficiency of tympanometric tests of Eustachian tube function (Valsalva test,
      Toynbee test and nine-step inflation/deflation test) in predicting ME barotrauma
      in 44 ears of 22 sports scuba divers who had normal audiometry, tympanometry and
      otorhinolaryngological examination without previous history of ear disease. The
      divers were counselled to refer to the investigators if any symptoms occurred
      during and/or after diving. All symptomatic ears were examined within 24 hours of
      diving by one investigator who was unaware of the pre-symptomatic test results.
      Decision matrix analysis was applied to the results of Eustachian tube function
      tests for predicting ears with barotrauma. Values were also evaluated for a
      battery of tests by 'Lax' (positive on A, B or C) and 'Strict' (positive on A, B
      and C) criteria. The nine-step test was found to be the most efficient (93%) test
      with highest predictive values (PPV 83%; NPV 95%), whereas the Valsalva and
      Toynbee tests were unreliable in predicting barotrauma, whereas the Valsalva and
      Toynbee tests were unreliable in predicting barotrauma (PPV of the Valsalva and
      Toynbee tests were 0% and 25% respectively). Combining the nine-step and Toynbee
      tests into a two-test battery in a strict approach increased the PPV (100%). It
      appears that the nine-step inflation/deflation test is a reliable method of
      predicting ME barotrauma sufferers, especially when applied with the Toynbee
      test. The nine-step test may have value in the evaluation of Eustachian tube
      function of sports scuba diving candidates after routine otorhinolaryngological,
      audiological and tympanometric evaluation.

PMID- 10905450
TI  - Use of a loudness model for hearing aid fitting. IV. Fitting hearing aids with
      multi-channel compression so as to restore 'normal' loudness for speech at
      different levels.
AB  - Many researchers have proposed that multi-channel compression hearing aids should
      process sounds so as to restore loudness perception to 'normal'. However,
      procedures for achieving this have generally been based on measurements or
      calculations using narrowband stimuli, and these procedures may not be accurate
      for broadband sounds such as speech. Here, a model for predicting loudness for
      people with cochlear hearing loss is used to calculate the frequency- and level
      dependent gains that would be required to restore loudness perception to 'normal'
      for speech-like signals. The calculations are based entirely on the pure tone
      audiogram, and do not require measures of loudness growth. The model was applied
      to several different hypothetical hearing losses, varying in slope and severity.
      In each case, the model was used to calculate the insertion gains (IGs) that
      would be required as a function of frequency so that speech-shaped noise with a
      level of 65 dB SPL would evoke a specific loudness pattern matching that for a
      normal ear. A similar procedure was applied using speech-shaped noise with a
      level of 85 dB SPL (with the spectral characteristics of shouted speech). The
      results were used to derive functions relating the required IG to hearing loss
      for each audiometric frequency and each speech-shaped noise level. These
      functions were used in turn to derive compression ratios and gains for each
      channel of a multi-channel compression system. The derivations apply to systems
      with any number of channels. The outcome is a method than can be used for the
      initial fitting of multichannel compression hearing aids, so as to restore
      loudness perception to near 'normal' for broadband speech-like signals.

PMID- 10905451
TI  - Assessment of the functioning of peripheral auditory pathways after cochlear re
      implantation in young children using intra-operative objective measures.
AB  - The intra-operative electrical auditory brainstem response (EABR), electrical
      stapedius reflex threshold (ESRT) and the early post-operative behavioural
      threshold level (T-level) were recorded in five children undergoing cochlear re
      implantation. The aim of the study was to assess objectively the effect of re
      implantation on intra-operative objective measures and to investigate neuronal
      function. The children were aged between 2.06 years and 4.5 years at first
      implantation. Following failure of the first device, re-implantation was carried
      out 1.42-5.52 years later. Characteristics of the EABR and ESRT across the
      electrode array were typical of the expected pattern of responses on both
      occasions. In particular, the slopes of the amplitude input/output (I/O)
      functions for wave eV of the intraoperative EABR were similar for both the first
      and second implants even though absolute thresholds were generally elevated after
      re-implantation. This elevation in intra-operative threshold was more pronounced
      than the change in early post-operative behavioural threshold level for
      electrical stimulation (T-level). Our findings confirm a high level of neuronal
      survival after re-implantation. Threshold of the intra-operative EABR at the time
      of re-implantation greatly underestimates the sensitivity of the subsequent early
      post-operative T-levels.

PMID- 10905452
TI  - Does having a job improve the quality of life among post-lingually deafened
      Swedish adults with severe-profound hearing impairment?
AB  - The purpose of the present study was to measure health-related quality of life
      (HRQL), personal harmony and work-induced problems, and to identify typical
      personal traits among Swedish adults with a severe-profound hearing impairment
      who were employed full-time. In comparison with hearing people aged <65 years,
      the hearing-impaired individuals working full-time differed only as regards
      energy and social isolation. Compared to another group of hearing-impaired
      subjects (working either part-time or retired) the study group scored better on
      most dimensions. Personal harmony of the hearing-impaired group working full-time
      did not differ from that of average employed Swedish people. The work situation
      of the group was generally reported to be busy but rewarding, especially
      concerning contact with fellow workers and management. Among various personal
      traits examined, strong will-power and stress tolerance were the most
      significant. However, due to the small sample size, it is not possible to state
      that the results indicate a general situation or were just due to the study
      subjects constituting an elite sample of hearing-impaired individuals.

PMID- 10905453
TI  - A computerized database of 'normal' auditory brainstem responses.
AB  - A computerized database of auditory brainstem responses (ABRs) from 'normal
      hearing' volunteers is described. The database contains 'raw' responses recorded
      from 81 individuals; subjects varied in age from 20 to 56 years. The database is
      currently being used in a study to aid in the interpretation of ABRs for
      diagnostic purposes. Copies of the database are available over the world-wide web
      (http:??www.engg.le.ac.uk?abrdata).

PMID- 10905454
TI  - Endothelial cell migration on surfaces modified with immobilized adhesive
      peptides.
AB  - Endothelial cell (EC) migration has been studied on aminophase surfaces with
      covalently bound RGDS and YIGSRG cell adhesion peptides. The fluorescent marker
      dansyl chloride was used to quantify the spatial distribution of the peptides on
      the modified surfaces. Peptides appeared to be distributed in uniformly dispersed
      large clusters separated by areas of lower peptide concentrations. We employed
      digital time-lapse video microscopy and image analysis to monitor EC migration on
      the modified surfaces and to reconstruct the cell trajectories. The persistent
      random walk model was then applied to analyze the cell displacement data and
      compute the mean root square speed, the persistence time, and the random motility
      coefficient of EC. We also calculated the time-averaged speed of cell locomotion.
      No differences in the speed of cell locomotion on the various substrates were
      noted. Immobilization of the cell adhesion peptides (RGDS and YIGSRG), however,
      significantly increased the persistence of cell movement and, thus, the random
      motility coefficient. These results suggest that immobilization of cell adhesion
      peptides on the surface of implantable biomaterials may lead to enhanced
      endothelization rates.

PMID- 10905455
TI  - Reactivity of a wollastonite-tricalcium phosphate Bioeutectic ceramic in human
      parotid saliva.
AB  - In a previous study, a new ceramic material (Bioeutectic), prepared by slow
      solidification through the eutectic temperature region of the wollastonite
      tricalcium phosphate system, was found to be reactive in a simulated body fluid.
      In the present study, the reactivity of the Bioeutectic was assessed in human
      parotid saliva. Samples of the material were soaked for one month in human
      parotid saliva at 37 degrees C. The experiments showed the formation of two
      separate zones of carbonate-hydroxyapatite-like phase on the periphery of the
      samples. The first zone was formed by reaction of the bioeutectic with the saliva
      and progressed inside the material. The other zone developed on the surface of
      the bioeutectic by precipitation from the media. The mechanism of carbonate
      hydroxyapatite-like phase formation in human parotid saliva appeared to be
      similar to that of apatite-like phase found in a simulated body fluid.

PMID- 10905456
TI  - Photocurable epoxy-polyol matrices for use in dental composites I.
AB  - There is a need for low shrinkage visible-light cure resins to replace the
      dimethacrylate polymers used in dental composites. Cycloaliphatic epoxy resins
      formulated with polyol network extenders have been considered as potential
      candidates to address this need. This paper presents basic materials
      characterisation to underpin the selection of epoxy-polyol matrices cured with
      cationic onium/camphorquinone initiators. The study investigates the effect of
      choice of polyol and the ratio of epoxy groups to polyol groups in the matrix
      (R). The limitations of some analytical methods are also discussed. Epoxy-polyols
      are shown to have significant advantages over dimethacrylates for dental as they
      exhibit: lower polymer shrinkage, no oxygen inhibition layer, higher strength,
      equivalent hardness and acceptable glass transition temperatures (by DMA).
      However, the mass increase of the epoxy-polyols materials in water at 37 degrees
      C is almost double that of the conventional dimethacrylate matrices and cracking
      was observed in some samples during hydration. It is demonstrated that this can
      be avoided by careful selection of the formulation parameters. The paper
      concludes that R should be selected to lie between the limits of 4 and 8 to
      ensure the matrix has a balance of acceptable properties. The reduction of the
      water-uptake of epoxy-polyol matrices remains an important target and will be
      addressed through further research.

PMID- 10905457
TI  - Electrodeposition of hydroxyapatite coatings in basic conditions.
AB  - Hydroxyapatite films have been grown in this work by an electrodeposition method
      involving both physical and chemical processes and presenting several differences
      with respect to other reported works. Description of the coating formation is
      based on the evolution of current through the sample placed as positive electrode
      in the basic electrolyte. The characterisation of hydroxyapatite films is of
      special importance since the bioactive properties related to HAP have been
      directly identified with its specific composition (Ca/P ratio) and crystalline
      structure. This characterisation has been traditionally fulfilled by the use of
      XRD, FTIR and SEM. Results of a further characterisation of the coatings by TEM
      and SFM, additional to the analysis by XRD, FTIR and SEM, are presented.
      Interpretation and comparison of our results with those obtained by other
      electrodeposition methods lead to arguments in favour of a deposition produced
      directly from ionic species.

PMID- 10905458
TI  - In vitro and in vivo evaluation of gelatin-chondroitin sulphate hydrogels for
      controlled release of antibacterial proteins.
AB  - Chemically cross-linked gelatin-chondroitin sulphate (ChS) hydrogels, impregnated
      in Dacron, were evaluated as drug delivery systems for antibacterial proteins.
      The gelatin-chondroitin sulphate gels, plain or impregnated in Dacron, were cross
      linked with a water-soluble carbodiimide (EDC) and N-hydroxysuccinimide (NHS).
      The release of lysozyme and recombinant thrombocidin (rTC-1), an antibacterial
      protein derived from human blood platelets, from the gelatin-ChS gels in Dacron
      in phosphate-buffered saline at 37 degrees C was determined, and compared to the
      release from gelatin gels in Dacron and plain gelatin-ChS gels. The incorporation
      of chondroitin sulphate into gelatin gels, caused a marked increase in lysozyme
      loading capacity, and a slower release rate. The relative release profiles for
      rTC-1 and lysozyme were equal for cross-linked gelatin as well as for cross
      linked gelatin-ChS gels. Furthermore, rTC-1 showed no loss of antibacterial
      activity after 1 week of release. The lysozyme concentration profiles in the
      samples and in the surrounding medium as a function of time were calculated using
      mathematical solutions for Ficks second law of diffusion for a semi-infinite
      composite medium, which is a schematic representation of a slab in a surrounding
      medium. The biocompatibility and degradation of the Dacron matrices impregnated
      with gelatin-ChS gels was studied after implantation in subcutaneous pockets in
      rats. Chemically cross-linked gelatin-Ch5 gels showed a mild tissue reaction, and
      almost complete degradation within 18 weeks of implantation.

PMID- 10905459
TI  - Improved biocompatibility of a viscous bioerodible poly(ortho ester) by
      controlling the environmental pH during degradation.
AB  - The poly(ortho ester), POE, used in this investigation, is a viscous bioerodible
      polymer (8 kDa), which rapidly degrades into a triol and an acidic by-product,
      acetic acid. In order to improve biocompatibility, we have evaluated the addition
      of various basic excipients, such as sodium acetate, hydroxyapatite, calcium
      carbonate and magnesium hydroxide, which buffered and neutralized the acidic
      degradation product and prolonged the polymer lifetime and drug release. This
      decrease of POE degradation rate results in a decreased rate of formation of the
      acidic by-product. Similarly, a POE of higher molecular weight (14 kDa) has been
      tested. Sodium acetate was too hydrophilic to affect the drug release and the
      biocompatibility of the polymer, whereas the presence of magnesium hydroxide
      markedly prolonged the drug release and improved the acceptability of the
      polymer. The increased molecular weight POE did not improve biocompatibility and
      a similar but delayed, inflammatory reaction was observed.

PMID- 10905460
TI  - Preparation of CM-chitin microspheres by complexation with iron(III) in w/o
      emulsion and their biodisposition characteristics in mice.
AB  - 6-O-Carboxymethylchitin (CM-chitin) was partially deacetylated by alkaline
      treatment, and the 30% deacetylated product was named CM-DA30 and used for the
      preparation of microspheres. An aqueous solution of CM-DA30 was added to hexane
      containing 1% (w/w) sorbitan sesquioleate and emulsified by stirring and
      sonication, and iron(III) chloride was added. The formed microspheres (CM-MS)
      were washed with methanol and lyophilized after addition of polyethylene glycol.
      The mean particle diameter was less than a few microm, and longer sonication time
      tended to decrease the mean particle size. Sixty min of sonication enabled the
      production of CM-MS consisting of only the particles with a diameter of less than
      several microm. Iron(III) content and recovery of CM-DA30 were not markedly
      affected by the sonication time. CM-MS was spherical as was observed by scanning
      electron microscopy. Fluorescein moieties-containing microspheres (CM-MS-FTC)
      were prepared in the same manner but using fluorescein-isothiocyanate-labeled CM
      DA30 (FTC-CM-DA30) instead of CM-DA30. After i.v. injection of CM-MS-FTC, its
      body distribution and urinary excretion of FTC-CM-DA30 were examined. CM-MS-FTC
      was located to some extent in the lung for an initial short time (= 1 h), soon
      cleared from the lung, and was retained for long in the liver and spleen. CM-MS
      FTC was quickly eliminated from the blood circulation, and 60% of the dose was
      excreted into urine at 3 h after injection. From 3 h after injection, the urinary
      excretion rate markedly decreased, and the total excreted amount was 66% of the
      dose at 12 h after injection, which was not significantly different from that at
      3 h after injection. The present preparation technique permits producing small
      microspheres of CM-chitin as a drug carrier possibly useful for the liver
      targeting.

PMID- 10905461
TI  - In vitro cytokine production by mononuclear cells exposed to bone cement
      extracts.
AB  - The authors evaluated the ability of bone cement to modify the profile of pro
      inflammatory cytokines secreted by the immune cells. Peripheral blood mononuclear
      cells (PBMC) collected from healthy individuals were cultured with cement
      extracts and tested to assess the release of IL-1beta, TNFalpha, GM-CSF and IL-6
      in both unstimulated and PHA-stimulated PBMC. The cytokine release of
      unstimulated PBMC was very poor, and in particular the IL-1beta was undetectable:
      the addition of cement extract increased both TNFalpha and GM-CSF release and
      decreased IL-6, sometimes significantly. The most recurrent observation in PHA
      stimulated PBMCs exposed to bone cement extract was the increase in both IL-1beta
      and IL-6 release, while both the mean concentration and the index of release of
      TNFalpha and GM-CSF were changeable. In conclusion our results showed that
      leachable components of some bone cements can induce in vitro the release of pro
      inflammatory cytokines which are known to be involved in the bone resorption
      associated with aseptic loosening of hip prostheses. These findings allowed us to
      identify materials endowed with the highest inflammatory power.

PMID- 10905462
TI  - Alginates from wound dressings activate human macrophages to secrete tumour
      necrosis factor-alpha.
AB  - Alginates are used to manufacture a number of wound dressings. Clinical
      observations indicate that they may initiate or accelerate healing of chronic
      wounds after treatment of underlying pathology. Wound granulation tissue contains
      large numbers of macrophages and they are thought to regulate the healing
      process. As purified alginates have been demonstrated to activate macrophages
      this study was initiated to determine whether alginates present within wound
      dressings may interact with wound macrophages. Alginate fibres taken from four
      commercially available dressings were co-cultured with the human histiocytic
      lymphoma cell line U937 following its differentiation with PMA. Activation was
      assessed by measurement of TNFalpha production. Two of the dressings, Seasorb and
      Tegagen, had a minimal effect whilst Sorbsan at 1 mg/ml induced 302 + 19 pg/ml
      TNFalpha. This effect was inhibited by polymyxin B indicating that activation was
      due to endotoxin contamination. Kaltostat induced production of 839 + 36 pg/ml
      TNFalpha. This effect was induced both by polymyxin inhibitable endotoxin and a
      direct interaction with the alginate fibres. These data indicate that some
      alginate containing dressings have the potential to activate macrophages within
      the chronic wound bed and generate a pro-inflammatory signal which may initiate a
      resolving inflammation characteristic of healing wounds.

PMID- 10905463
TI  - Enhanced functions of osteoblasts on nanophase ceramics.
AB  - Select functions of osteoblasts (bone-forming cells) on nanophase (materials with
      grain sizes less than 100 nm) alumina, titania, and hydroxyapatite (HA) were
      investigated using in vitro cellular models. Compared to conventional ceramics,
      surface occupancy of osteoblast colonies was significantly less on all nanophase
      ceramics tested in the present study after 4 and 6 days of culture. Osteoblast
      proliferation was significantly greater on nanophase alumina, titania, and HA
      than on conventional formulations of the same ceramic after 3 and 5 days. More
      importantly, compared to conventional ceramics, synthesis of alkaline phosphatase
      and deposition of calcium-containing mineral was significantly greater by
      osteoblasts cultured on nanophase than on conventional ceramics after 21 and 28
      days. The results of the present study provided the first evidence of enhanced
      long-term (on the order of days to weeks) functions of osteoblasts cultured on
      nanophase ceramics; in this manner, nanophase ceramics clearly represent a unique
      and promising class of orthopaedic/dental implant formulations with improved
      osseointegrative properties.

PMID- 10905464
TI  - Gene transfer into hepatoma cells mediated by galactose-modified alpha-helical
      peptides.
AB  - To develop a receptor-mediated gene delivery system into hepatoma cells using the
      cationic alpha-helical peptide as the gene carrier molecule, we modified an alpha
      helical peptide, which is known to have transfection abilities into cells, with a
      multi-antennary ligand containing several galactose residues that provide
      efficient binding to the asialoglycoprotein receptor. The galactose-modified
      peptides formed complexes with a plasmid DNA and showed gene transfer abilities
      into HuH-7 cells, a human hepatoma cell line. The transfection efficiency of the
      peptide was increased by increasing the number of modified galactose residues on
      the peptide. Furthermore, considerable inhibition of the transfection efficiency
      by the addition of asialofetuin, which is a ligand for the asialoglycoprotein
      receptor, was observed in all galactose-modified peptides. Based on this result,
      we could confirm that the internalization of the galactose-modified peptides
      occurred by the receptor-mediated endocytosis pathway. In addition, to understand
      the transport route of the peptide-DNA complex in the cell, the effects on the
      transfection efficiencies with several endocytosis inhibitors were examined. As a
      result, it was suggested that the translocation of the peptide-DNA complex from
      the endocytic compartments to the cytosol mainly occurred during an early
      endosome step.

PMID- 10905465
TI  - Emerging cell and molecular strategies for the study and treatment of painful
      peripheral neuropathies.
AB  - Pharmacologic treatment for the symptoms of painful neuropathy has been
      problematic, because there has been limited understanding of the underlying
      etiologies and systemic levels that an effective dose can have on multiple side
      effects. The use of molecular methods, such as gene deletion from knockout mice
      and cellular minipumps for delivery of biologic antinociceptive molecules, has
      led to a better understanding of the underlying mechanisms of the induction of
      intractable neuropathic pain. The initiation of an excitatory cascade after
      injury or disease leads to the induction of various second messenger systems,
      loss or down-regulation of the endogenous inhibitory spinal GABA system and
      central sensitization, causing such pain. The development and use of cellular
      minipumps, immortalized cell lines bioengineered to secrete various
      antinociceptive molecules for the reversal of neuropathic pain, makes cellular
      therapy a strategy for clinical use in the next few years. The development of
      molecular "disimmortalization" technologies will make the use of such engineered
      cell lines safe for human use. Direct somatic gene transfer for neuropathic pain
      will eventually overcome the problems associated with transplantation of non
      autologous and xenogenic cells. These virus-mediated methods, although at the
      early stages of evolution and use, offer large-scale production of biologic
      agents that can be conveniently and confidently used for the long-term relief of
      chronic neuropathic pain in a clinical setting, without systemic effects or
      surgical interventions.

PMID- 10905466
TI  - Increased expression of chemokines (MCP-1, MIP-1alpha, RANTES) after peripheral
      nerve transection.
AB  - After nerve injury, recruitment of circulating macrophages into the endoneurium
      is essential for degeneration and subsequently for successful regeneration.
      However, the factors leading to macrophage recruitment are not known in detail.
      Chemokines are one of many possible factors influencing recruitment. In this
      study we wanted to examine, immunohistochemically, the expression of MCP-1, MIP
      1alpha and RANTES from 6 hours up to 4 weeks after transection of rat sciatic
      nerve. An increased expression of MCP-1 was noted already 6 hours after
      transection, mainly in Schwann cells. Later, the MCP-1 positive staining was seen
      also in macrophages, fibroblast-like cells and endothelial cells. An increased
      number of MIP-1alpha positive cells could be noticed after 24 hours, the maximum
      expression in Schwann cells was noted at the 5-day timepoint. Later, part of the
      positive cells appeared to be macrophages. RANTES was mainly expressed in
      inflammatory cells. Endothelial cells in the epi- and endoneurium showed positive
      staining for every chemokine studied after transection. The contralateral non
      operated nerves showed an increased number of positive cells for MCP-1 and MIP
      1alpha. In the control nerves MCP-1 and MIP-1alpha positive cells were scattered
      throughout the endoneurium. This study shows that increased expression of
      chemokines takes place within endoneurium after peripheral nerve transection.
      Thus, it is probable that chemokines can take part in the recruitment of
      macrophages. It further shows that there is an increased expression of the
      studied chemokines in the non-operated contralateral nerves. Even in normal
      conditions chemokines are needed, probably to keep resident macrophages within
      endoneurium.

PMID- 10905467
TI  - Post reinnervation maturation of myelinated nerve fibers in the cat tibial nerve:
      chronic electrophysiological and morphometric studies.
AB  - The extent to which the long-term recovery of nerve fibers differs according to
      the cause of Wallerian degeneration is not clear, although outgrowth of axons is
      better after lesions with continuity of basal lamina of the Schwann cell tubes
      (nerve crush) compared with lesions with interruption of basal lamina (nerve
      section). Post-reinnervation maturation of myelinated nerve fibers of the cat
      tibial nerve was followed in chronic electrophysiologic studies after crushing,
      sectioning, and section+freeze lesions, and compared with morphometric analysis
      of the same nerves. The amplitudes of the compound nerve action potentials
      (CNAPs) recovered to a much lesser extent after sectioning than after crushing
      the nerve. This difference could be related to a smaller number of large fibers,
      a greater degree of sprouting after sectioning than after crushing, or less
      synchronization of conduction in regenerated fibers. In comparison, the compound
      muscle action potentials (CMAPs) recovered to a greater extent than the CNAP
      after sectioning and section+freeze, though not to the same degree or as fast as
      after crushing. The difference between the recovery of the CNAP and the CMAP
      could be due to better regeneration of motor fibers, to differences in the size
      of motor units or to a better summation of motor unit action potentials. The
      maximal conduction velocities (CV) in mixed nerve and in motor fibers increased
      faster after crushing than after sectioning and section+freeze to 60%-70% of
      control values. The diameters of the largest myelinated fibers increased in all
      lesions to about 80% of controls. The relation between fiber diameter and CV was
      influenced by remodeling of myelin during maturation. Hence, long-term functional
      recovery is influenced by the nature of the nerve lesion, and a smaller
      proportion of fibers recovered functionally after nerve section than after crush.

PMID- 10905468
TI  - Epineurial application of TNF elicits an acute mechanical hyperalgesia in the
      awake rat.
AB  - Tumor necrosis factor alpha (TNF) injected into the sciatic nerve and
      neutralizing antibodies to its receptor injected around the nerve are
      respectively associated with inducing and blocking pain behavior beginning 1 to 3
      days post-injection. This study examined the acute effects of TNF applied around
      the nerve trunk on the mechanical threshold (determined with von Frey hairs) and
      withdrawal latency to radiant heat. TNF (0.9 and 7.7 ng in 90 microL) injected
      onto the nerve via an indwelling catheter elicited a decrease in mechanical
      threshold. Following the low dose of TNF, no change in thermal latency was
      observed; after the 7.7 ng dose, thermal thresholds decreased and returned to
      baseline multiple times within the 3-hour observation period. Identical doses of
      TNF injected near, but not on the nerve, 90 ng of TNF injected on the nerve, and
      vehicle were without effect on either modality. These data indicate that effects
      of acutely administered TNF to the nerve trunk are capable of producing modality
      specific pain behavior. These changes may represent a first step in TNF-induced
      neuropathic pain.

PMID- 10905469
TI  - Peroneal neuropathy after weight loss.
AB  - The objectives of this study were to evaluate the clinical and
      electrophysiological findings in peroneal mononeuropathies following a weight
      reduction diet. Thirty patients with acute peroneal palsy and weight loss were
      studied. Complete nerve conduction studies (NCS) were performed in upper and
      lower limbs. NCS showed conduction block (CB) of the peroneal nerve at the
      fibular head that recovered in 29 patients within 3 weeks to 3 months. Severity
      of CB was correlated with clinical weakness. Three patients had abnormalities
      consistent with polyneuropathy (PNP). NCS in asymptomatic relatives confirmed
      familial neuropathy. Nerve biopsy and molecular study were consistent with
      hereditary neuropathy with liability to pressure palsies (HNPP). One of these
      peroneal palsies (6 months) recovered after neurolysis. Weight loss might be a
      risk factor in peroneal mononeuropathies. NCS is a tool in the diagnosis of the
      site and severity of the nerve injury. Testing should be considered for relatives
      of patients with PNP because peroneal mononeuropathies may be the first
      expression of HNPP.

PMID- 10905470
TI  - Severe polyneuropathy in a patient with Churg-Strauss syndrome.
AB  - We describe the clinicopathologic features of a 56-year-old woman affected with
      Churg-Strauss syndrome with major peripheral nerve involvement. The patient
      presented with a 1-month history of mainly distal upper-limb symmetrical
      paresthesias and hypostenia (bilateral "wrist drop"), palpable purpura and
      eosinophilia. Multiple pulmonary infiltrates and asthma had been present since
      the age of 52. Skin biopsy demonstrated an eosinophilic necrotizing vasculitis.
      During the hospitalization she was submitted to cardiac, bronchopulmonary, renal,
      and gastrointestinal evaluation and EMG. Peripheral nerve and skeletal muscle
      biopsies were performed. Sural nerve biopsy showed a marked degree of
      demyelination. A perivascular cellular infiltrate within the epineurium was
      immunoreactive for T lymphocytes and macrophages. Strong HLA-DR immunostaining
      was present in the endoneurium. IgM, IgE and fibrinogen deposition was found in
      some epi- and endoneurial vessels. Muscle biopsy showed neurogenic changes and 1
      thrombosed vessel surrounded by mononuclear cells. Membrane attack complex (MAC)
      deposition was present in a few capillaries and major histocompatibility complex
      products I (MHCP I) was expressed at the subsarcolemmal level in a few isolated
      perivascular muscle fibers. After immunosuppressive therapy, the patient showed
      progressive improvement of both clinical symptoms and neurophysiological
      parameters.

PMID- 10905471
TI  - Inexcitability of nerves in a fulminant case of Guillain-Barre syndrome.
AB  - A 45-year-old woman presented with a recent sensorimotor deficiency in all 4
      limbs, and the next day she was totally paralyzed. A slight motor improvement
      began on day 27. The cerebrospinal fluid had normal cellularity, but the protein
      varied from 90 mg/dL on the first day to 800 mg/dL on day 15, and then 290 mg/dL
      on day 33. Electrophysiologic studies performed on days 15 and 23 revealed a
      universal peripheral nerve inexcitability. A superficial peroneal nerve biopsy
      was performed on day 23. Nine fascicles were examined on semi-thin sections and
      myelinated fiber damage varied greatly from one fascicle to another. At
      ultrastructural examination, certain axons were severely damaged, but the others
      were quite well preserved and were naked or wrapped in a myelin sheath presenting
      a multivesicular degeneration. A few fibers had a better-preserved myelin sheath
      that was sometimes dissociated by elongated processes from an invading
      histiocyte. Six cases of fulminant Guillain-Barre syndrome with inexcitability of
      nerves and ultrastructural examination of nerve fragments have been reported.
      Electrophysiologic study is often ambiguous and cannot determine the precise
      origin of such an axonal degeneration. Therefore, ultrastructural analysis of a
      nerve biopsy is mandatory in this setting.

PMID- 10905472
TI  - Fuel selection in human skeletal muscle in insulin resistance: a reexamination.
AB  - For many years, the Randle glucose fatty acid cycle has been invoked to explain
      insulin resistance in skeletal muscle of patients with type 2 diabetes or
      obesity. Increased fat oxidation was hypothesized to reduce glucose metabolism.
      The results of a number of investigations have shown that artificially increasing
      fat oxidation by provision of excess lipid does decrease glucose oxidation in the
      whole body. However, results obtained with rodent or human systems that more
      directly examined muscle fuel selection have found that skeletal muscle in
      insulin resistance is accompanied by increased, rather than decreased, muscle
      glucose oxidation under basal conditions and decreased glucose oxidation under
      insulin-stimulated circumstances, producing a state of "metabolic inflexibility."
      Such a situation could contribute to the accumulation of triglyceride within the
      myocyte, as has been observed in insulin resistance. Recent knowledge of insulin
      receptor signaling indicates that the accumulation of lipid products in muscle
      can interfere with insulin signaling and produce insulin resistance. Therefore,
      although the Randle cycle is a valid physiological principle, it may not explain
      insulin resistance in skeletal muscle.

PMID- 10905473
TI  - Mice with gene disruption of both endothelial and neuronal nitric oxide synthase
      exhibit insulin resistance.
AB  - Studies from our laboratory using acute pharmacologic blockade of nitric oxide
      synthase (NOS) activity have suggested that nitric oxide (NO) has an important
      role in regulating carbohydrate metabolism. We now report on insulin sensitivity
      in mice with targeted disruptions in endothelial NOS (eNOS) and neuronal NOS
      (nNOS) genes compared with their wild-type (WT) counterparts. Mice underwent
      hyperinsulinemic-euglycemic clamp studies after a 24-h fast, during an insulin
      infusion of 20 mU x kg(-1) x min(-1). Glucose levels were measured at baseline
      and every 10 min during the clamp. Insulin levels were measured at baseline and
      at the end of the clamp study. Glucose infusion rates (GIRs) during the last 30
      min of the clamp study were in a steady state. Tritiated glucose infusion was
      used to measure rates of endogenous glucose output (EGO) both at baseline and
      during steady-state euglycemia. Glucose disposal rates (GDRs) were computed from
      the GIR and EGO. Fasting and steady-state glucose and insulin levels were
      comparable in the 3 groups of mice. No differences in fasting EGO were noted
      between the groups. GIR was significantly reduced (37%, P = 0.001) in the eNOS
      knockout (KO) mice compared with the WT mice, with values for the nNOS mice being
      intermediate. EGO was completely suppressed in the nNOS and WT mice during
      insulin infusion, but not in the eNOS mice. Even so, the eNOS mice displayed
      significantly reduced whole-body GDRs compared with those of the WT mice (82.67+/
      10.77 vs. 103.67+/-3.47 mg x kg(-1) x min(-1), P = 0.03). eNOS KO mice are
      insulin resistant at the level of the liver and peripheral tissues, whereas the
      nNOS KO mice are insulin resistant only in the latter. These data indicate that
      NO plays a role in modulating insulin sensitivity and carbohydrate metabolism and
      that the eNOS isoform may play a dominant role relative to nNOS.

PMID- 10905474
TI  - Secretion of tumor necrosis factor-alpha shows a strong relationship to insulin
      stimulated glucose transport in human adipose tissue.
AB  - Some animal models suggest that tumor necrosis factor (TNF)-alpha is a key
      component in obesity-linked insulin resistance because it inhibits insulin
      receptor signaling and glucose transport in insulin-sensitive tissues. However,
      in vivo data in humans have given conflicting results regarding the relationship
      between circulating TNF-alpha levels and insulin sensitivity. In the present
      study, the potential local role of TNF-alpha on insulin action in human
      subcutaneous adipose tissue was studied in 42 obese women (BMI 39+/-10 kg/m2). We
      found a strong inverse correlation between adipose TNF-alpha secretion and
      maximum insulin-stimulated glucose transport in adipocytes that was independent
      of fat cell volume, age, and BMI (P < 0.001, r = 0.58). As much as one-third of
      the variation in insulin-stimulated glucose transport could be accounted for by
      variations in TNF-alpha secretion. There was no significant correlation (r =
      0.11) between secretion of adipose plasminogen activator inhibitor 1 and glucose
      transport. Furthermore, subcutaneous adipose tissue of 4 obese women (BMI 40+/-4)
      incubated with TNF-A for 24 h showed a one-third concentration-dependent
      inhibition of insulin-stimulated glucose transport (P < 0.01). In conclusion,
      adipose TNF-alpha may be an important specific and local factor in adipose tissue
      that influences the ability of insulin to stimulate glucose transport in human
      fat cells, at least in obese women.

PMID- 10905475
TI  - Localization of glucokinase gene expression in the rat brain.
AB  - The brain contains a subpopulation of glucosensing neurons that alter their
      firing rate in response to elevated glucose concentrations. In pancreatic beta
      cells, glucokinase (GK), the rate-limiting enzyme in glycolysis, mediates glucose
      induced insulin release by regulating intracellular ATP production. A similar
      role for GK is proposed to underlie neuronal glucosensing. Via in situ
      hybridization, GK mRNA was localized to hypothalamic areas that are thought to
      contain relatively large populations of glucosensing neurons (the arcuate,
      ventromedial, dorsomedial, and paraventricular nuclei and the lateral area). GK
      also was found in brain areas without known glucosensing neurons (the lateral
      habenula, the bed nucleus stria terminalis, the inferior olive, the
      retrochiasmatic and medial preoptic areas, and the thalamic posterior
      paraventricular, interpeduncular, oculomotor, and anterior olfactory nuclei).
      Conversely, GK message was not found in the nucleus tractus solitarius, which
      contains glucosensing neurons, or in ependymal cells lining the third ventricle,
      where others have described its presence. In the arcuate nucleus, >75% of
      neuropeptide Y-positive neurons also expressed GK, and most GK+ neurons also
      expressed KIR6.2 (the pore-forming subunit of the ATP-sensitive K+ channel). The
      anatomic distribution of GK mRNA was confirmed in micropunch samples of
      hypothalamus via reverse transcription-polymerase chain reaction (RT-PCR).
      Nucleotide sequencing of the recovered PCR product indicated identity with
      nucleotides 1092-1411 (within exon 9 and 10) of hepatic and beta-cell GK. The
      specific anatomic localization of GK mRNA in hypothalamic areas known to contain
      glucosensing neurons and the coexpression of KIR6.2 and NPY in GK+ neurons
      support a role for GK as a primary determinant of glucosensing in neuropeptide
      neurons that integrate multiple signals relating to peripheral energy metabolism.

PMID- 10905477
TI  - Acceleration of type 1 diabetes by a coxsackievirus infection requires a
      preexisting critical mass of autoreactive T-cells in pancreatic islets.
AB  - Coxsackievirus infections have been proposed as an environmental trigger for the
      development of T-cell-mediated autoimmune (type 1) diabetes by either providing a
      molecular mimic of the candidate pancreatic beta-cell autoantigen GAD or inducing
      bystander inflammation in the pancreas. In this study in the NOD mouse model, we
      found that infection with a pancreatrophic coxsackievirus isolate can accelerate
      type 1 diabetes development through the induction of a bystander activation
      effect, but only after a critical threshold level of insulitic beta-cell
      autoreactive T-cells has accumulated. Thus, coxsackievirus infections do not
      appear to initiate beta-cell autoreactive immunity but can accelerate the process
      once it is underway. These findings indicate that the timing of a coxsackievirus
      infection, rather than its simple presence or absence, may have important
      etiological implications for the development of T-cell-mediated autoimmune type 1
      diabetes in humans.

PMID- 10905476
TI  - Effects of free fatty acid elevation on postabsorptive endogenous glucose
      production and gluconeogenesis in humans.
AB  - Effects of free fatty acids (FFAs) on endogenous glucose production (EGP) and
      gluconeogenesis (GNG) were examined in healthy subjects (n = 6) during stepwise
      increased Intralipid/heparin infusion (plasma FFAs 0.8+/-0.1, 1.8+/-0.2, and
      2.8+/-0.3 mmol/l) and during glycerol infusion (plasma FFAs approximately 0.5
      mmol/l). Rates of EGP were determined with D-[6,6-2H2]glucose and contributions
      of GNG from 2H enrichments in carbons 2 and 5 of blood glucose after 2H2O
      ingestion. Plasma glucose concentrations decreased by approximately 10% (P <
      0.01), whereas plasma insulin increased by approximately 47% (P = 0.02) after 9 h
      of lipid infusion. EGP declined from 9.3+/-0.5 (lipid) and 9.0+/-0.8 pmol x kg(
      1) x min(-1) (glycerol) to 8.4+/-0.5 and 8.2+/-0.7 micromol x kg(-1) x min(-1),
      respectively (P < 0.01). Contribution of GNG similarly rose (P < 0.01) from 46+/
      4 and 52+/-3% to 65+/-8 and 78+/-7%. To exclude interaction of FFAs with insulin
      secretion, the study was repeated at fasting plasma insulin (approximately 35
      pmol/l) and glucagon (approximately 90 ng/ml) concentrations using somatostatin
      insulin-glucagon clamps. Plasma glucose increased by approximately 50% (P <
      0.005) during lipid but decreased by approximately 12% during glycerol infusion
      (P < 0.005). EGP remained unchanged over the 9-h period (9.9+/-1.2 vs. 9.0+/-1.1
      micromol x kg(-1) x min(-1)). GNG accounted for 62+/-5 (lipid) and 60+/-6%
      (glycerol) of EGP at time 0 and rose to 74+/-3% during lipid infusion only (P <
      0.05 vs. glycerol: 64+/-4%). In conclusion, high plasma FFA concentrations
      increase the percent contribution of GNG to EGP and may contribute to increased
      rates of GNG in patients with type 2 diabetes.

PMID- 10905478
TI  - Cerulenin, an inhibitor of protein acylation, selectively attenuates nutrient
      stimulation of insulin release: a study in rat pancreatic islets.
AB  - Nutrients such as glucose stimulate insulin release from pancreatic beta-cells
      through both ATP-sensitive K+ channel-independent and -dependent mechanisms,
      which are most likely interrelated. Although little is known of the molecular
      basis of ATP-sensitive K+ channel-independent insulinotropic nutrient actions,
      mediation by cytosolic long-chain acyl-CoA has been implicated. Because protein
      acylation might be a sequel of cytosolic long-chain acyl-CoA accumulation, we
      examined if this reaction is engaged in nutrient stimulation of insulin release,
      using cerulenin, an inhibitor of protein acylation. In isolated rat pancreatic
      islets, cerulenin inhibited the glucose augmentation of Ca2+-stimulated insulin
      release evoked by a depolarizing concentration of K+ in the presence of diazoxide
      and Ca2+-independent insulin release triggered by a combination of forskolin and
      phorbol ester under stringent Ca2+-free conditions. Cerulenin inhibition of
      glucose effects was concentration dependent, with a 50% inhibitory concentration
      (IC50) of 5 microg/ml and complete inhibition at 100 microg/ml. Cerulenin also
      inhibited augmentation of insulin release by alpha-ketoisocaproate, a
      mitochondrial fuel. Furthermore, cerulenin abolished augmentation of both Ca2+
      stimulated and Ca2+-independent insulin release by 10 micromol/l palmitate, which
      causes palmitoylation of cellular proteins. In contrast, cerulenin did not
      attenuate insulin release elicited by nonnutrient secretagogues, such as a
      depolarizing concentration of K+, activators of protein kinases A and C, and
      mastoparan. Glucose oxidation, ATP content in islets, and palmitate oxidation
      were not affected by cerulenin. In conclusion, cerulenin inhibits nutrient
      augmentation of insulin release with a high selectivity. The finding is
      consistent with a prominent role of protein acylation in the process of beta-cell
      nutrient sensing.

PMID- 10905479
TI  - Glucose-regulated anaplerosis and cataplerosis in pancreatic beta-cells: possible
      implication of a pyruvate/citrate shuttle in insulin secretion.
AB  - The hypothesis proposing that anaplerosis and cataplerosis play an important role
      in fuel signaling by providing mitochondrially derived coupling factors for
      stimulation of insulin secretion was tested. A rise in citrate coincided with the
      initiation of insulin secretion in response to glucose in INS-1 beta-cells. The
      dose dependence of glucose-stimulated insulin release correlated closely with
      those of the cellular contents of citrate, malate, and citrate-derived malonyl
      CoA. The glucose-induced elevations in citrate, alpha-ketoglutarate, malonyl-CoA,
      and the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium reduction state, an
      index of beta-cell metabolic activity, were unaffected by the Ca2+ chelator EGTA.
      Glucose induced a rise in both mitochondrial and cytosolic citrate and promoted
      efflux of citrate from the cells. The latter amounted to approximately 20% of
      glucose carbons entering the glycolytic pathway. Phenylacetic acid, a pyruvate
      carboxylase inhibitor, reduced the glucose-induced rise in citrate in INS-1 cells
      and insulin secretion in both INS-1 cells and rat islets. The results indicate
      the feasibility of a pyruvate/citrate shuttle in INS-1 beta-cells, allowing the
      regeneration of NAD+ in the cytosol and the formation of cytosolic acetyl-CoA,
      malonyl-CoA, and NADPH. The data suggest that anaplerosis and cataplerosis are
      early signaling events in beta-cell activation that do not require a rise in
      Ca2+. It is proposed that citrate is a signal of fuel abundance that contributes
      to beta-cell activation in both the mitochondrial and cytosolic compartments and
      that a major fate of anaplerotic glucose carbons is external citrate.

PMID- 10905480
TI  - Cx36 preferentially connects beta-cells within pancreatic islets.
AB  - Previous studies have provided evidence for the transcripts of Cx43 and Cx45
      within pancreatic islets. As of yet, however, it has proven difficult to
      unambiguously demonstrate the expression of these proteins by islet cells. We
      have investigated whether Cx36, a new connexin species recently identified in
      mammalian brain and retina, may also be expressed in pancreatic islets. Using
      probes that permitted the original identification of Cx36 in the central nervous
      system, we show that a transcript for Cx36 is clearly detectable in rat
      pancreatic islets. Using novel and affinity-purified polyclonal antibodies, we
      have found that Cx36 is actually expressed in pancreatic islets. Both in situ
      hybridization and immunolabeling indicated that this connexin is abundant in the
      centrally located insulin-producing beta-cells and is expressed much less, if at
      all, by the other endocrine cell types. This differential expression was further
      confirmed on fluorescence-activated cell sorter-purified preparations enriched in
      either beta- or non-beta-cells. The finding of a differential distribution of
      Cx36 within distinct regions of pancreatic islets creates the possibility that
      this connexin may provide the establishment of selective pathways of
      communication between the different types of endocrine cells comprising the
      pancreatic islet.

PMID- 10905481
TI  - Metformin restores insulin secretion altered by chronic exposure to free fatty
      acids or high glucose: a direct metformin effect on pancreatic beta-cells.
AB  - Because metformin affects glucose and free fatty acid (FFA) metabolism in
      peripheral insulin target tissues, we investigated the effect of this drug in
      restoring a normal secretory pattern in rat pancreatic islets whose function has
      been impaired by chronic exposure to elevated FFA or glucose concentrations. We
      cultured rat pancreatic islets with or without FFA (2 mmol/l oleate/palmitate
      2:1) or high glucose (16.7 mmol/l) concentrations in the presence or absence of
      metformin (0.25-12.5 microg/ml) and then measured insulin release, glucose
      utilization, glucose, and FFA oxidation. When compared with control islets,
      islets exposed to high FFA or glucose concentrations showed an increased basal
      and a decreased glucose-induced insulin release. In islets cultured for an
      additional 24 h with FFA or glucose in the presence of metformin (2.5 microg/ml),
      both basal and glucose-induced insulin secretions were restored. Both glucose
      utilization and glucose oxidation were altered in islets pre-exposed to high FFA
      or glucose concentrations. In particular, regarding control islets, glucose
      utilization was increased at 2.8 mmol/l glucose and decreased at 16.7 mmol/l
      glucose; glucose oxidation was similar to control islets at 2.8 mmol/l glucose
      but decreased at 16.7 mmol/l glucose. In contrast, oleate oxidation was increased
      in islets pre-exposed to FFA. All of these abnormalities were reversed in islets
      cultured for an additional 24 h with high FFA or glucose concentrations in the
      presence of metformin (2.5 microg/ml). In conclusion, our data show that
      metformin is able to restore the intracellular abnormalities of glucose and FFA
      metabolism and to restore a normal secretory pattern in rat pancreatic islets
      whose secretory function has been impaired by chronic exposure to elevated FFA or
      glucose levels. These data raise the possibility that, in diabetic patients,
      metformin (in addition to its peripheral effects) may have a direct beneficial
      effect on the beta-cell secretory function.

PMID- 10905482
TI  - Insulinotropic glucagon-like peptide 1 agonists stimulate expression of
      homeodomain protein IDX-1 and increase islet size in mouse pancreas.
AB  - Diabetes is caused by a failure of the pancreas to produce insulin in amounts
      sufficient to meet the body's needs. A hallmark of diabetes is an absolute (type
      1) or relative (type 2) reduction in the mass of pancreatic beta-cells that
      produce insulin. Mature beta-cells have a lifespan of approximately 48-56 days
      (rat) and are replaced by the replication of preexisting beta-cells and by the
      differentiation and proliferation of new beta-cells (neogenesis) derived from the
      pancreatic ducts. Here, we show that the insulinotropic hormone glucagon-like
      peptide (GLP)-1, which is produced by the intestine, enhances the pancreatic
      expression of the homeodomain transcription factor IDX-1 that is critical for
      pancreas development and the transcriptional regulation of the insulin gene.
      Concomitantly, GLP-1 administered to diabetic mice stimulates insulin secretion
      and effectively lowers their blood sugar levels. GLP-1 also enhances beta-cell
      neogenesis and islet size. Thus, in addition to stimulating insulin secretion,
      GLP-1 stimulates the expression of the transcription factor IDX-1 while
      stimulating beta-cell neogenesis and may thereby be an effective treatment for
      diabetes.

PMID- 10905483
TI  - Hepatic fat content and insulin action on free fatty acids and glucose metabolism
      rather than insulin absorption are associated with insulin requirements during
      insulin therapy in type 2 diabetic patients.
AB  - To determine causes of interindividual variation in insulin requirements, we
      recruited 20 type 2 diabetic patients with stable glucose control and insulin
      doses for >1 year on combination therapy with bedtime NPH insulin and metformin.
      Insulin absorption (increase in free and total insulin over 8 h after a
      subcutaneous dose of regular insulin) and actions of intravenous (6-h 0.3 mU x
      kg(-1) x min(-1) euglycemic insulin clamp combined with [3-3H]glucose) and
      subcutaneous (glucose infusion rate required to maintain isoglycemia and
      suppression of free fatty acids [FFAs]) insulin, liver fat content (proton
      spectroscopy), visceral fat (magnetic resonance imaging), weight, and body
      composition were determined. We found the following variation in parameters:
      insulin dose range 10-176 U (mean 42 U, fold variation 17.6x) or 0.13-1.39 U/kg
      (0.44 U/kg, 10.7x), absorbed insulin 10.6x, action of subcutaneous insulin to
      suppress FFAs 7.5 x and to stimulate glucose metabolism (M value) 11.5x, body
      weight 67-127 kg (91 kg, 1.9x), liver fat 2-28% (12%, 14x), and visceral fat 179
      2,053 ml (1,114 ml, 11.5x). The amount of insulin absorbed, measured as either
      free or total insulin, was significantly correlated with its ability to suppress
      FFAs and stimulate glucose metabolism but not with the insulin dose per se. The
      actions of absorbed insulin were, on the other hand, significantly correlated
      with the daily insulin dose (r = 0.70 for action on FFAs, P < 0.001, and r = 
      0.61 for M value, P < 0.005). Actions of subcutaneous and intravenous insulin to
      suppress FFAs were significantly correlated (r = 0.82, P < 0.001, R2 = 67%). Of
      the measures of adiposity, the percent hepatic fat was the parameter best
      correlated with the daily insulin dose (r = 0.76, P < 0.001). The percent hepatic
      fat was also significantly correlated with the ability of intravenous insulin to
      suppress endogenous glucose production (r = 0.72, P < 0.005). We conclude that
      the major reason for interindividual variation in insulin requirements in type 2
      diabetes is the variation in insulin action. Variation in hepatic fat content may
      influence insulin requirements via an effect on the sensitivity of endogenous
      glucose production to insulin.

PMID- 10905484
TI  - A new thiazolidinedione, NC-2100, which is a weak PPAR-gamma activator, exhibits
      potent antidiabetic effects and induces uncoupling protein 1 in white adipose
      tissue of KKAy obese mice.
AB  - Thiazolidinediones (TZDs) reduce insulin resistance in type 2 diabetes by
      increasing peripheral uptake of glucose, and they bind to and activate the
      transcriptional factor peroxisome proliferator-activated receptor-gamma (PPAR
      gamma). Studies have suggested that TZD-induced activation of PPAR-gamma
      correlates with antidiabetic action, but the mechanism by which the activated
      PPAR-gamma is involved in reducing insulin resistance is not known. To examine
      whether activation of PPAR-gamma directly correlates with antidiabetic
      activities, we compared the effects of 4 TZDs (troglitazone, pioglitazone, BRL
      49653, and a new derivative, NC-2100) on the activation of PPAR-gamma in a
      reporter assay, transcription of the target genes, adipogenesis, plasma glucose
      and triglyceride levels, and body weight using obese KKAy mice. There were 10- to
      30-fold higher concentrations of NC-2100 required for maximal activation of PPAR
      gamma in a reporter assay system, and only high concentrations of NC-2100 weakly
      induced transcription of the PPAR-gamma but not PPAR-alpha target genes in a
      whole mouse and adipogenesis of cultured 3T3L1 cells, which indicates that NC
      2100 is a weak PPAR-gamma activator. However, low concentrations of NC-2100
      efficiently lowered plasma glucose levels in KKAy obese mice. These results
      strongly suggest that TZD-induced activation of PPAR-gamma does not directly
      correlate with antidiabetic (glucose-lowering) action. Furthermore, NC-2100
      caused the smallest body weight increase of the 4 TZDs, which may be partly
      explained by the finding that NC-2100 efficiently induces uncoupling protein
      (UCP)-2 mRNA and significantly induces UCP1 mRNA in white adipose tissue (WAT).
      NC-2100 induced UCP1 efficiently in mesenteric WAT and less efficiently in
      subcutaneous WAT, although pioglitazone and troglitazone also slightly induced
      UCP1 only in mesenteric WAT. These characteristics of NC-2100 should be
      beneficial for humans with limited amounts of brown adipose tissue.

PMID- 10905485
TI  - Interaction between insulin sensitivity and muscle perfusion on glucose uptake in
      human skeletal muscle: evidence for capillary recruitment.
AB  - Insulin and glucose delivery (muscle perfusion) can modulate insulin-mediated
      glucose uptake. This study was undertaken to determine 1) to what extent insulin
      sensitivity modulates the effect of perfusion on glucose uptake and 2) whether
      this effect is achieved via capillary recruitment. We measured glucose disposal
      rates (GDRs) and leg muscle glucose uptake (LGU) in subjects exhibiting a wide
      range of insulin sensitivity, after 4 h of steady-state (SS) euglycemic
      hyperinsulinemia (>6,000 pmol/l) and subsequently after raising the rate of leg
      blood flow (LBF) 2-fold with a superimposed intrafemoral artery infusion of
      methacholine chloride (Mch), an endothelium-dependent vasodilator. LBF was
      determined by thermodilution: LGU = arteriovenous glucose difference (AVGdelta) x
      LBF. As a result of the 114+/-12% increase in LBF induced by Mch, the AVGdelta
      decreased 32+/-4%, and overall rates of LGU increased 40+/-5% (P < 0.05). We
      found a positive relationship between the Mch-modulated increase in LGU and
      insulin sensitivity (GDR) (r = 0.60, P < 0.02), suggesting that the most insulin
      sensitive subjects had the greatest enhancement of LGU in response to
      augmentation of muscle perfusion. In separate groups of subjects, we also
      examined the relationship between muscle perfusion rate and glucose extraction
      (AVGdelta). Perfusion was either pharmacologically enhanced with Mch or reduced
      by intra-arterial infusion of the nitric oxide inhibitor N(G)-monomethyl-L
      arginine during SS euglycemic hyperinsulinemia. Over the range of LBF, changes in
      AVGdelta were smaller than expected based on the noncapillary recruitment model
      of Renkin. Together, the data indicate that 1) muscle perfusion becomes more rate
      limiting to glucose uptake as insulin sensitivity increases and 2) insulin
      mediated increments in muscle perfusion are accompanied by capillary recruitment.
      Thus, insulin-stimulated glucose uptake displays both permeability- and perfusion
      limited glucose exchange properties.

PMID- 10905486
TI  - Targeted upregulation of pyruvate dehydrogenase kinase (PDK)-4 in slow-twitch
      skeletal muscle underlies the stable modification of the regulatory
      characteristics of PDK induced by high-fat feeding.
AB  - In using Western blot analysis with antibodies raised against recombinant
      pyruvate dehydrogenase kinase (PDK) isoforms PDK2 and PDK4, this study
      demonstrates selective PDK isoform switching in specific skeletal muscle types in
      response to high-fat feeding that is associated with altered regulation of PDK
      activity by pyruvate. The administration of a diet high in saturated fats led to
      stable (approximately 2-fold) increases in PDK activities in both a typical slow
      twitch (soleus [SOL]) muscle and a typical fast-twitch (anterior tibialis [AT])
      muscle. Western blot analysis revealed that high-fat feeding significantly
      increased (approximately 2-fold; P < 0.001) PDK4 protein expression in SOL, with
      a modest (1.3-fold) increase in PDK2 protein expression. The relative increase in
      PDK4 protein expression in SOL was associated with a 7.6-fold increase in the
      pyruvate concentration that was required to elicit a 50% active pyruvate
      dehydrogenase complex, which indicates a marked decrease in the sensitivity of
      PDK to inhibition by pyruvate. In AT muscle, high-fat feeding elicited comparable
      (1.5- to 1.7-fold) increases (P < 0.05) in PDK4 and PDK2 protein expression. Loss
      of sensitivity of PDK to inhibition by pyruvate was less marked. The data suggest
      that a positive correlation exists between increases in PDK4 expression and the
      propensity with which muscles use lipid-derived fuels as respiratory substrates
      rather than with the degree of insulin resistance induced in skeletal muscles by
      high-fat feeding. In conclusion, high-fat feeding leads to selective upregulation
      of PDK4 expression in slow-twitch muscle in response to high-fat feeding in vivo,
      which is associated with a pronounced loss of sensitivity of PDK activity to
      acute inhibition by pyruvate. Thus, increased PDK4 expression may underlie the
      stable modification of the regulatory characteristics of PDK observed in slow
      twitch muscle in response to high-fat feeding.

PMID- 10905487
TI  - Response of pancreatic beta-cells to improved insulin sensitivity in women at
      high risk for type 2 diabetes.
AB  - The purpose of this study was to examine the response of pancreatic beta-cells to
      changes in insulin sensitivity in women at high risk for type 2 diabetes. Oral
      glucose tolerance tests (OGTTs) and frequently sampled intravenous glucose
      tolerance tests (FSIGTs) were conducted on Latino women with impaired glucose
      tolerance and a history of gestational diabetes before and after 12 weeks of
      treatment with 400 mg/day troglitazone (n = 13) or placebo (n = 12). Insulin
      sensitivity was assessed by minimal model analysis, and beta-cell insulin release
      was assessed as acute insulin responses to glucose (AIRg) and tolbutamide (AIRt)
      during FSIGTs and as the 30-min incremental insulin response (30-min dINS) during
      OGTTs. Beta-cell compensation for insulin resistance was assessed as the product
      (disposition index) of minimal model insulin sensitivity and each of the 3
      measures of beta-cell insulin release. In the placebo group, there was no
      significant change in insulin sensitivity or in any measure of insulin release,
      beta-cell compensation for insulin resistance, or glucose tolerance. Troglitazone
      treatment resulted in a significant increase in insulin sensitivity, as reported
      previously. In response, AIRg did not change significantly, so that the
      disposition index for AIRg increased significantly from baseline (P = 0.004) and
      compared with placebo (P = 0.02). AIRt (P = 0.001) and 30-min dINS (P = 0.02)
      fell with improved insulin sensitivity during troglitazone treatment, so that the
      disposition index for each of these measures of beta-cell function did not change
      significantly from baseline (P > 0.20) or compared with placebo (P > 0.3).
      Minimal model analysis revealed that 89% of the change from baseline in insulin
      sensitivity during troglitazone treatment was accounted for by lowered plasma
      insulin concentrations. Neither oral nor intravenous glucose tolerance changed
      significantly from baseline or compared with placebo during troglitazone
      treatment. The predominant response of beta-cells to improved insulin sensitivity
      in women at high risk for type 2 diabetes was a reduction in insulin release to
      maintain nearly constant glucose tolerance.

PMID- 10905489
TI  - Rates of skeletal muscle and adipose tissue glycerol release in nonobese and
      obese subjects.
AB  - Skeletal muscle and adipose tissue lipolysis rates were quantitatively compared
      in 12 healthy nonobese and 14 insulin-resistant obese subjects for 3.5 h after an
      oral glucose load using microdialysis measurements of interstitial glycerol
      concentrations and determinations of local blood flow with 133Xe clearance in the
      gastrocnemius muscle and in abdominal subcutaneous adipose tissue. Together with
      measurements of arterialized venous plasma glycerol, the absolute rates of
      glycerol mobilization were estimated. In the basal state, skeletal muscle and
      adipose tissue glycerol levels were 50% higher (P < 0.05-0.01) and adipose tissue
      blood flow (ATBF) and muscle blood flow (MBF) rates were 30-40% lower (P < 0.02
      0.05) in obese versus nonobese subjects. After glucose ingestion, adipose tissue
      glycerol levels were rapidly and transiently reduced, whereas in muscle, a
      progressive and less pronounced fall in glycerol levels was evident. MBF remained
      unchanged in both study groups, whereas ATBF increased more markedly (P < 0.01)
      in the nonobese versus obese subjects after the oral glucose load. The fasting
      rates of glycerol release per unit of tissue weight from skeletal muscle were
      between 20 and 25% of that from adipose tissue in both groups. After glucose
      ingestion, the rates of glycerol release from skeletal muscle and from adipose
      tissue were almost identical in nonobese and obese subjects. However, the kinetic
      patterns differed markedly between tissues; in adipose tissue, the rate of
      glycerol mobilization was suppressed by 25-30% (P < 0.05) after glucose
      ingestion, whereas no significant reduction was registered in skeletal muscle. We
      conclude that significant amounts of glycerol are released from skeletal muscle,
      which suggests that muscle lipolysis provides an important endogenous energy
      source in humans. In response to glucose ingestion, the regulation of skeletal
      muscle glycerol release differs from that in adipose tissue; although the rate of
      glycerol release from adipose tissue is clearly suppressed, the rate of glycerol
      mobilization from skeletal muscle remains unaltered. In quantitative terms, the
      rate of glycerol release per unit of tissue weight in adipose tissue and in
      skeletal muscle is similar in nonobese and obese subjects in both the
      postabsorptive state and after glucose ingestion.

PMID- 10905488
TI  - IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein
      metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino
      acid clamp.
AB  - Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I
      axis. Such abnormalities include decreased circulating levels of IGF-I. We
      studied the effects of IGF-I therapy (40 microg x kg(-1) x day(-1)) on protein
      and glucose metabolism in adults with type 1 diabetes in a randomized placebo
      controlled trial. A total of 12 subjects participated, and each subject was
      studied at baseline and after 7 days of treatment, both in the fasting state and
      during a hyperinsulinemic-euglycemic amino acid clamp. Protein and glucose
      metabolism were assessed using infusions of [1-13C]leucine and [6-6-2H2]glucose.
      IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P <
      0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05).
      After IGF-I treatment, a decrease in the overnight insulin requirement (0.26+/
      0.07 vs. 0.17+/-0.06 U/kg, P < 0.05) and an increase in the glucose infusion
      requirement were observed during the hyperinsulinemic clamp (approximately 67%, P
      < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin
      stimulated peripheral glucose disposal was observed after IGF-I therapy (37+/-6
      vs. 52+/-10 micromol x kg(-1) x min(-1), P < 0.05). IGF-I administration
      increased the basal metabolic clearance rate for leucine (approximately 28%, P <
      0.05) and resulted in a net increase in leucine balance, both in the basal state
      and during the hyperinsulinemic amino acid clamp (-0.17+/-0.03 vs. -0.10+/-0.02,
      P < 0.01, and 0.25+/-0.08 vs. 0.40+/-0.06, P < 0.05, respectively). No changes in
      these variables were recorded in the subjects after administration of placebo.
      These findings demonstrated that IGF-I replacement resulted in significant
      alterations in glucose and protein metabolism in the basal and insulin-stimulated
      states. These effects were associated with increased insulin sensitivity, and
      they underline the major role of IGF-I in protein and glucose metabolism in type
      1 diabetes.

PMID- 10905490
TI  - Delayed insulin transport across endothelium in insulin-resistant JCR:LA-cp rats.
AB  - Capillary endothelial cells are thought to limit the transport of insulin across
      the endothelium, resulting in attenuated insulin action at target sites. Whether
      endothelial insulin transport is altered in dysglycemic insulin-resistant states
      is not clear and was therefore investigated in the JCR:LA-cp corpulent male rat,
      which exhibits the metabolic syndrome of obesity, insulin resistance,
      hyperlipidemia, and hyperinsulinemia. Lean littermates that did not develop these
      alterations served as controls. Animals of both groups were normotensive (mean
      arterial pressure 136+/-2 mmHg). Hearts from obese and lean rats aged 7 (n = 6)
      or 18 (n = 8) weeks were perfused in vitro at 10 ml/min per gram wet wt over 51
      min with Krebs-Henseleit buffer containing 0.1 or 0.5 U human insulin/l
      (equivalent to 0.6 and 3 nmol/l). Interstitial fluid was collected using a
      validated method, and interstitial insulin was determined with a
      radioimmunoassay. At 0.1 U/l, insulin transfer velocity was similar in both
      experimental groups (half-times of transfer: 11+/-0.2 min in obese and 18+/-4 min
      in lean rats; NS), but at 0.5 U/l, the respective half-times were 7+/-1 min in
      lean and 13+/-2 min in obese rats (P < 0.05). The steady-state level of insulin
      in the interstitium was 34+/-1% of the vascular level at 0.1 U/l and reached the
      vascular level (102+/-2%) at 0.5 U/l in both lean and obese rats. In rats aged 18
      weeks, the half-times of insulin transfer were 31+/-2 and 14+/-l min in obese
      rats and 10+/-0.3 and 7+/-0.3 min in lean rats (P < 0.05). Again, interstitial
      steady-state levels were similar in both groups. Finally, postprandial insulin
      dynamics were simulated over a period of 120 min with a peak concentration of 0.8
      U/l in rats aged 27 weeks (n = 4). The maximal interstitial level was 0.38+/-0.02
      U/l in lean rats and 0.24+/-0.02 U/l in obese rats (P < 0.05), and a similar
      difference was noted throughout insulin infusion (areas under the transudate
      concentration-time curves: 17 and 11 U/min per 1, respectively). These data show,
      for the first time in a genetic animal model of insulin resistance, that transfer
      of insulin across the endothelium is substantially delayed in obese insulin
      resistant rats and that it likely contributes to the postprandial alterations of
      glucose metabolism observed in the metabolic syndrome.

PMID- 10905491
TI  - Tumor necrosis factor-alpha induces hepatic insulin resistance in obese Zucker
      (fa/fa) rats via interaction of leukocyte antigen-related tyrosine phosphatase
      with focal adhesion kinase.
AB  - The molecular mechanism whereby tumor necrosis factor-alpha (TNF-alpha) induces
      insulin resistance in obesity is not well understood. Previously, we have shown
      that inhibition of TNF-alpha improved hepatic insulin sensitivity in obese Zucker
      rats without altering the tyrosine phosphorylation of liver insulin receptors
      (IRs), which indicates that the TNF-alpha and insulin-signaling cascades interact
      distally to the IR. To assess the effects of TNF-alpha on signaling molecules
      downstream from the IR, we analyzed the tyrosine phosphorylation patterns of
      liver homogenate proteins from TNF-alpha-neutralized fa/fa rats and showed that
      focal adhesion kinase (FAK) was consistently hyperphosphorylated (4.5-fold).
      Moreover, intravenous insulin increased hepatic FAK phosphorylation in a time
      dependent manner in Sprague-Dawley rats, which suggests that TNF-alpha may induce
      hepatic insulin resistance by preventing FAK phosphorylation in response to
      insulin treatment. To explore the cellular mechanism whereby TNF-alpha regulates
      phosphorylation of FAK in the liver, we measured c-Src kinase activity and the
      abundance of 3 major protein tyrosine phosphatases (PTPs) (PTP-1B, leukocyte
      antigen-related tyrosine phosphatase [LAR], and src homology 2 domain-containing
      protein-tyrosine phosphatase [SHPTP-2]) in liver homogenates from obese Zucker
      rats after TNF-alpha blockade. Hepatic c-Src kinase activity was unaltered, but
      LAR protein was reduced by 75%. In addition, TNF-alpha blockade reduced hepatic
      PTP activity toward tyrosine phosphorylated FAK by 70%, and this was accounted
      for by immunodepletion of LAR. Incubation of HepG2 cells with TNF-alpha increased
      LAR protein levels in a dose-dependent manner. Additionally, pretreatment with
      TNF-alpha abolished insulin-stimulated tyrosine phosphorylation of FAK in HepG2
      cells but had no effect on IR tyrosine phosphorylation or expression. These data
      suggest that TNF-alpha promotes LAR expression and thus prevents insulin-mediated
      tyrosine phosphorylation of FAK. This probably represents the interface between
      TNF-alpha and insulin signaling in the liver.

PMID- 10905492
TI  - Presumed apoptosis and reduced arcuate nucleus neuropeptide Y and pro
      opiomelanocortin mRNA in non-coma hypoglycemia.
AB  - Hypoglycemia reduces sympathoadrenal responses to subsequent hypoglycemic bouts
      by an unknown mechanism. To assess whether such hypoglycemia-associated autonomic
      failure is due to actual brain damage, male Sprague-Dawley rats underwent 1-h
      bouts of insulin-induced (5 U/kg i.v.) hypoglycemia (1.6-2.8 mmol/l) 1 or 3 times
      on alternate days. Rats remained alert and were rescued with intravenous glucose
      at 60-80 min. Plasma epinephrine and corticosterone responses were significantly
      reduced during the second and third bouts. Brains from these rats were processed
      by the terminal transferase-mediated deoxyuridine triphosphate-biotin nick end
      labeling (TUNEL) procedure as an index of apoptotic cell death at 24, 48, or 96 h
      after their first bout. At 48 h, but not 24 h, TUNEL+ cells were consistently
      seen only in the arcuate nucleus (arcuate hypothalamic nucleus [ARC]).
      Hypoglycemic rats had 188% more apoptotic ARC cells (1 bout 39+/-5; 3 bouts 37+/
      4) than euglycemic controls (13+/-3;P = 0.001). In situ hybridization for
      neuropeptide Y (NPY) and proopiomelanocortin (POMC) mRNA was performed in
      sections of ARC containing maximal numbers of apoptotic cells as well as in other
      fresh frozen brains. After 1 bout, NPY (0.041+/-0.003) and POMC (0.119+/-0.022)
      mRNA were decreased, respectively, by 52 and 55% vs. controls (NPY 0.076+/-0.007;
      POMC 0.222+/-0.020; P = 0.01). NPY (0.029+/-0.002) but not POMC (0.093+/-0.013)
      fell 29% further after a third bout. NPY (r = -0.721; P = 0.001) and POMC (r = 
      0.756; P = 0.001) mRNA levels correlated negatively with the number of apoptotic
      ARC cells in the same sections. Thus, non-coma hypoglycemia produces apparent
      apoptotic cell death with reduced NPY and POMC expression selectively in the ARC.
      This may contribute to the reduced counterregulatory response following repeated
      bouts of hypoglycemia.

PMID- 10905493
TI  - Mechanism of troglitazone action in type 2 diabetes.
AB  - To examine the metabolic pathways by which troglitazone improves insulin
      responsiveness in patients with type 2 diabetes, the rate of muscle glycogen
      synthesis was measured by 13C-nuclear magnetic resonance (NMR) spectroscopy. The
      rate-controlling steps of insulin-stimulated muscle glucose metabolism were
      assessed using 31P-NMR spectroscopic measurement of intramuscular glucose-6
      phosphate (G-6-P) combined with a novel 13C-NMR method to assess intracellular
      glucose concentrations. Seven healthy nonsmoking subjects with type 2 diabetes
      were studied before and after completion of 3 months of troglitazone (400 mg/day)
      therapy. After troglitazone treatment, rates of insulin-stimulated whole-body
      glucose uptake increased by 58+/-11%, from 629+/-82 to 987+/-156 micromol x m(-2)
      x min(-1) (P = 0.008), which was associated with an approximately 3-fold increase
      in rates of insulin-stimulated glucose oxidation (from 119+/-41 to 424+/-70
      micromol x m(-2) x min(-1); P = 0.018) and muscle glycogen synthesis (26+/-17 vs.
      83+/-35 micromol x l(-1) muscle x min(-1); P = 0.025). After treatment, muscle G
      6-P concentrations increased by 0.083+/-0.019 mmol/l (P = 0.008 vs. pretreatment)
      during the hyperglycemic-hyperinsulinemic clamp, compared with no significant
      changes in intramuscular G-6-P concentrations in the pretreatment study,
      reflecting an improvement in glucose transport and/or hexokinase activity. The
      concentrations of intracellular free glucose did not differ between the pre- and
      posttreatment studies and remained >50-fold lower in concentration (<0.1 mmol/l)
      than what would be expected if hexokinase activity was rate-controlling. These
      results indicate that troglitazone improves insulin responsiveness in skeletal
      muscle of patients with type 2 diabetes by facilitating glucose transport
      activity, which thereby leads to increased rates of muscle glycogen synthesis and
      glucose oxidation.

PMID- 10905494
TI  - Genotype/phenotype relationships in HNF-4alpha/MODY1: haploinsufficiency is
      associated with reduced apolipoprotein (AII), apolipoprotein (CIII),
      lipoprotein(a), and triglyceride levels.
AB  - Hepatocyte nuclear factor (HNF)-4alpha is a transcription factor that plays an
      important role in regulation of gene expression in pancreatic beta-cells and in
      the liver. Heterozygous mutations in the HNF-4alpha gene are responsible for
      maturity-onset diabetes of the young 1 (MODY1), which is characterized by
      pancreatic beta-cell-deficient insulin secretion. HNF-4alpha is a major
      transcriptional regulator of many genes expressed in the liver. However, no liver
      defect has been identified in individuals with HNF-4alpha mutations. In this
      study, we have identified HNF-4alpha target genes that are mainly expressed in
      the liver, including alpha1-antitrypsin, alpha1-antichymotrypsin, alpha-fetal
      protein, ceruloplasmin, IGF binding protein 1, transferrin, apolipoprotein(AI)
      [apo(AI)], apo(AII), apo(B), and apo(CIII). Serum levels of these proteins and
      Lp(a) and triglycerides were measured in 24 members of the HNF-4alpha/MODY1 RW
      pedigree (Q268X mutation), including 12 diabetic patients with HNF-4alpha
      mutations (D-HNF4+/-), 6 nondiabetic subjects with HNF-4alpha mutations (N-HNF4+/
      ), 6 normal relatives (N-HNF4+/+), 6 unrelated normal matched control subjects (N
      HNF4+/+), and 12 matched diabetic (non-MODY1-5) patients (D-HNF4+/+). Serum
      levels of apo(AII), apo(CIII), lipoprotein(a) [Lp(a)], and triglyceride were
      significantly reduced in HNF4+/- subjects (26.9, 19.8, 12.1, and 72.1 mg/dl,
      respectively) compared with HNF4+/+ subjects (37.4, 26.5, 45.2, and 124.2 mg/dl,
      respectively) (P = 0.00001, P = 0.01, P = 0.00006, and P = 0.000003,
      respectively). This reduction was not found when apo(AII), apo(CIII), Lp(a), and
      triglyceride levels were compared in D-HNF4+/- versus N-HNF4+/- or in D-HNF4+/+
      versus N-HNF4+/+ subjects, which indicates that HNF-4alpha haploinsufficiency
      rather than hyperglycemia is the primary cause of decreased serum protein and
      triglyceride concentrations. Furthermore, we determined that genetic or
      environmental modifiers other than HNF-4alpha do not appear to contribute to the
      observed decrease of HNF-4alpha-regulated serum proteins. This study demonstrates
      that a heterozygous HNF-4alpha mutation leads to an HNF-4alpha-dependent
      hepatocyte secretory defect of liver-specific proteins.

PMID- 10905495
TI  - Differential brain responses to satiation in obese and lean men.
AB  - Knowledge of how the brain contributes to the regulation of food intake in humans
      is limited. We used positron emission tomography and measures of regional
      cerebral blood flow (rCBF) (a marker of neuronal activity) to describe the
      functional anatomy of satiation (i.e., the response to a liquid meal) in the
      context of extreme hunger (36-h fast) in 11 obese (BMI > or =35 kg/m2, age 27+/-5
      years, weight 115+/-11 kg, 38+/-7% body fat; mean +/- SD) and 11 lean (BMI < or
      =25 kg/m2, age 35+/-8 years, weight 73+/-9 kg, 19+/-6% body fat) men. As in lean
      men, satiation in obese men produced significant increases in rCBF in the
      vicinity of the ventromedial and dorsolateral prefrontal cortex and significant
      decreases in rCBF in the vicinity of the limbic/paralimbic areas (i.e.,
      hippocampal formation, temporal pole), striatum (i.e., caudate, putamen),
      precuneus, and cerebellum. However, rCBF increases in the prefrontal cortex were
      significantly greater in obese men than in lean men (P < 0.005). rCBF decreases
      in limbic/paralimbic areas, temporal and occipital cortex, and cerebellum were
      also significantly greater in obese men than in lean men (P < 0.005), whereas
      rCBF decreases in the hypothalamus and thalamus were attenuated in obese men
      compared with lean men (P < 0.05). This study raises the possibility that the
      brain responses to a meal in the prefrontal areas (which may be involved in the
      inhibition of inappropriate response tendencies) and limbic/paralimbic areas
      (commonly associated with the regulation of emotion) may be different in obese
      and lean men. Additional studies are required to investigate how these
      differential responses are related to the pathophysiology of obesity.

PMID- 10905496
TI  - Divergent regulation of Akt1 and Akt2 isoforms in insulin target tissues of obese
      Zucker rats.
AB  - To determine whether impaired Akt (protein kinase B or rac) activation
      contributes to insulin resistance in vivo, we examined the expression,
      phosphorylation, and kinase activities of Akt1 and Akt2 isoforms in insulin
      target tissues of insulin-resistant obese Zucker rats. In lean rats, insulin (10
      U/kg i.v. x 2.5 min) stimulated Akt1 activity 6.2-, 8.8-, and 4.4-fold and Akt2
      activity 5.4-, 9.3-, and 1.8-fold in muscle, liver, and adipose tissue,
      respectively. In obese rats, insulin-stimulated Akt1 activity decreased 30% in
      muscle and 21% in adipose tissue but increased 37% in liver compared with lean
      littermates. Insulin-stimulated Akt2 activity decreased 29% in muscle and 37% in
      liver but increased 24% in adipose tissue. Akt2 protein levels were reduced 56%
      in muscle and 35% in liver of obese rats, but Akt1 expression was unaltered.
      Phosphoinositide 3-kinase (PI3K) activity associated with insulin receptor
      substrate (IRS)-1 or phosphotyrosine was reduced 67-86% in tissues of obese rats
      because of lower IRS-1 protein levels and reduced insulin receptor and IRS-1
      phosphorylation. In adipose tissue of obese rats, in spite of an 86% reduction in
      insulin-stimulated PI3K activity, activation of Akt2 was increased. Maximal
      insulin-stimulated (100 nmol/l) glucose transport was reduced 70% in isolated
      adipocytes, with a rightward shift in the insulin dose response for transport and
      for Akt1 stimulation but normal sensitivity for Akt2. These findings suggest that
      PI3K-dependent effects on glucose transport in adipocytes are not mediated
      primarily by Akt2. Akt1 and Akt2 activations by insulin have a similar time
      course and are maximal by 2.5 min in adipocytes of both lean and obese rats. We
      conclude that 1) activation of Akt1 and Akt2 in vivo is much less impaired than
      activation of PI3K in this insulin-resistant state, and 2) the mechanisms for
      divergent alterations in insulin action on Akt1 and Akt2 activities in tissues of
      insulin-resistant obese rats involve tissue- and isoform-specific changes in both
      expression and activation.

PMID- 10905497
TI  - Nitric oxide synthesis and isoprostane production in subjects with type 1
      diabetes and normal urinary albumin excretion.
AB  - The role of nitric oxide (NO) and free radicals in the development of
      microvascular disease in type 1 diabetes remains unclear. We have measured NO and
      isoprostane (a stable marker of in vivo lipid peroxidation) production in 13 type
      1 diabetic subjects with normal urinary albumin excretion and 13 healthy
      volunteers. Whole-body NO synthesis was quantified by measuring the urinary
      excretion of 15N-nitrate after the intravenous administration of L-[15N]2
      arginine. The urinary excretion of the major urinary metabolite of 15-F2t
      isoprostane (8-iso-prostaglandin-F2alpha), 2,3-dinor-5,6-dihydro-F2t-IsoP, was
      quantified as a marker of in vivo lipid peroxidation. Whole-body NO synthesis was
      significantly higher in diabetic subjects compared with control subjects (342 vs.
      216 nmol 15N-nitrate/mmol creatinine [95% CI of the difference 45-207], P =
      0.005). This increase was not explained by a difference in renal function between
      the 2 groups. There was no difference in 2,3-dinor-5,6-dihydro-F2t-IsoP excretion
      between diabetic subjects and control subjects (44.8+/-7.8 vs. 41.4+/-10.0
      ng/mmol creatinine, mean +/- 95% CI). However, there was an inverse correlation
      between NO synthesis and free radical activity in subjects with diabetes (r = 
      0.62, P = 0.012) that was not observed in control subjects (r = 0.37, P = 0.107).
      We conclude that whole-body NO synthesis is higher in type 1 diabetic subjects
      with normal urinary albumin excretion than in control subjects. The inverse
      correlation between isoprostane production and NO synthesis in diabetic subjects
      is consistent with the hypothesis that NO is being inactivated by reactive oxygen
      species.

PMID- 10905498
TI  - Glucosamine activates the plasminogen activator inhibitor 1 gene promoter through
      Sp1 DNA binding sites in glomerular mesangial cells.
AB  - Increased flux through the hexosamine biosynthetic pathway is associated with
      altered gene expression. To investigate the underlying mechanisms, we treated
      glomerular mesangial cells with glucosamine and studied the regulation of the
      plasminogen activator inhibitor (PAI)-1 gene. Incubating mesangial cells with 2
      mmol/l glucosamine for 4 days resulted in a 3.1+/-0.4-fold increase in PAI-1 mRNA
      levels (P < 0.01) and a 33+/-9-fold increase in the activity of a transiently
      transfected PAI-1 promoter-luciferase reporter gene (P < 0.01). Cotransfection of
      an expression vector for a dominant-negative type II TGF-beta receptor with the
      PAI-1 promoter-reporter gene did not interfere with this effect of glucosamine.
      However, mutation of 2 putative Sp1 sites in the PAI-1 promoter, at -76 to -71
      and -44 to -39, markedly reduced induction of PAI-1 luciferase activity by
      glucosamine, from 8.9+/-1.9-fold to 1.7+/-0.5-fold (P < 0.01). An electrophoretic
      mobility shift assay demonstrated that glucosamine increased Sp1 DNA binding by
      31+/-11% (P < 0.05), implying that the effects of glucosamine were explained, in
      part, by changes in Sp1 DNA binding. High glucose (20 mmol/l) also activated the
      transiently transfected PAI-1 promoter (2.5+/-0.4-fold). This effect was
      diminished by mutation of both the PAI-1 promoter Sp1 sites (1.2+/-0.3-fold, P <
      0.05). In addition, 6-diazo-5-oxo-L-norleucine, a glutamine:fructose-6-phosphate
      amidotransferase inhibitor, blocked the induction by high glucose (4.7+/-0.8- to
      0.9+/-0.1-fold, P < 0.01). These results indicate that stimulation of the PAI-1
      promoter by both high glucose and glucosamine involves Sp1 and that the
      hexosamine pathway may be involved in the regulation of gene expression by high
      glucose in glomerular mesangial cells.

PMID- 10905499
TI  - The CART gene and human obesity: mutational analysis and population genetics.
AB  - The cocaine- and amphetamine-regulated transcript (CART) peptide is a recently
      characterized neuropeptide implicated in the control of appetite. We hypothesized
      that genetic variation in CART may contribute to human obesity. The entire coding
      region of CART was determined by nucleotide sequencing in 91 unrelated subjects
      with severe early-onset obesity. A novel amino acid change, Ser66Thr, was found
      in 2 probands and in 0 of 100 control subjects but did not cosegregate with
      obesity in family studies. Two common polymorphisms were found in the 3'
      untranslated region (A1475G and deltaA1457). An effect of these polymorphisms on
      body composition and intermediate phenotypes related to obesity was examined in a
      large Caucasian population in the U.K. Neither polymorphism showed any
      significant relationship with obesity; however, men heterozygous for the A1475G
      variant had significantly lower waist-to-hip ratio (WHR), fasting plasma insulin,
      and fasting triglycerides. Regression analysis indicated that the effects on
      insulin and triglycerides were likely to be secondary to the effects on WHR.
      Thus, we have conducted the first systematic study of the CART gene in human
      obesity, and although no clear association with obesity was found, the data
      suggest that genetic variation in the CART locus might influence fat distribution
      and variables related to syndrome X.

PMID- 10905500
TI  - NeuroD/BETA2 gene variability and diabetes: no associations to late-onset type 2
      diabetes but an A45 allele may represent a susceptibility marker for type 1
      diabetes among Danes. Danish Study Group of Diabetes in Childhood, and the Danish
      IDDM Epidemiology and Genetics Group.
AB  - Mutations in the NeuroD/BETA2 gene have been shown to associate with type 2
      diabetes. In the present study, we examined mutations in the NeuroD/BETA2 gene
      for association with either type 1 or 2 diabetes. Three variants were identified
      in patients with type 2 diabetes: Ala45Thr (allelic frequency 0.36, 95% CI 0.31
      0.41), Pro197His (0.01), and Ser259Ser (0.01). Ala45Thr and Pro197His were not
      associated with type 2 diabetes, but the transmission disequilibrium test showed
      unequal transmission of the A45 allele to offspring with type 1 diabetes (chi2 =
      5.90, P < 0.02, odds ratio 1.55, 95% CI 0.91-2.63). This association could not be
      explained by linkage disequilibrium between the Ala45 allele and IDDM7 (D2S152),
      which is also located on chromosome 2q32. When tested in vitro, the biological
      activity of Thr45 (117+/-36% vs. Ala45) and His197 (90+/-28% vs. Pro197) on the
      regulation of the human insulin gene promoter appeared normal. In conclusion,
      mutations in the NeuroD/BETA2 gene are not a common cause of late-onset type 2
      diabetes among Danes. However, in the type 1 diabetic Danish population, the
      Ala45Thr variant of NeuroD/BETA2 may represent a susceptibility marker
      independent of IDDM7 on chromosome 2q32.

PMID- 10905501
TI  - A distinct mutational spectrum of p53 and K-ras genes in lung cancer of workers
      with silicosis.
AB  - Crystalline silica was recently classified as a human carcinogen by the
      International Agency for Research on Cancer (IARC). However, the direct genotoxic
      effect of silica in humans remains unclear. We examined the p53 and K-ras gene
      mutations in lung cancer in workers with silicosis (LCWS). DNA was extracted from
      paraffin-embedded tissues and examined by PCR-RFLP, PCR-SSCP, and DNA sequencing.
      The mutation frequencies of p53 gene were high, but the mutation distributions in
      exons and among the histological types of LCWS differed from those of common
      (i.e., not silicosis-related) lung cancer. Furthermore, no mutations in codon 12
      of K-ras gene (predominant in common lung cancer) were found in LCWS. These
      findings in the mutational spectrum support a carcinogenic effect of silica dust
      at the DNA molecular level.

PMID- 10905502
TI  - Cytotoxic effects of 5-fluorocytosine on melanoma cells transduced with cytosine
      deaminase gene.
AB  - To investigate the cytotoxic effects of 5-fluorocytosine on melanoma cells
      genetically modified with cytosine deaminase gene, the gene was transduced into
      the tumor cells with the retroviral method. The cytotoxicity effects of 5
      fluorocytosine on the tumor cells were measured with the MTT assay and clonogenic
      assay. It was found that the prodrug 5-fluorocytosine had significant cytotoxic
      effects on melanoma cells transduced with cytosine deaminase in vitro. The IC50
      value of 5-fluorocytosine on transgenic and nontransgenic melanoma cells was 572
      microg/mL(-1) and 3870 microg/mL(-1), respectively. Our experiment demonstrated
      the potential value of the cytosine deaminase gene/5-fluorocytosine system in the
      treatment of melanoma.

PMID- 10905503
TI  - DNA damage and activation of c-ras in human embryo lung cells exposed to
      chrysotile and cigarette smoking solution.
AB  - Epidemiological studies and animal experiments showed that asbestos and cigarette
      smoking can act synergistically in the development of lung cancer. The mechanism
      of this synergism is largely unknown. It is well documented that DNA damage and
      activation of oncogenes play important roles in the development of cancer. The
      aim of our study was to find out if DNA damage could be increased and c-ras
      oncogene could be activated when human embryo lung cells were treated with
      chrysotile (CH) and cigarette smoking solution (CSS) separately or
      simultaneously. Human embryo lung (HEL) cells were treated with different doses
      of CH and CSS separately or simultaneously, then DNA strand breaks were detected
      with single-cell gel electrophoresis assay and the expression of p21 was detected
      by flow cytometry. Factorial analysis was used to evaluate the combined effect of
      chrysotile and cigarette smoking solution. The results showed that DNA strand
      breaks could be increased significantly when HEL cells were exposed to CH and CSS
      separately for 1 hour and increased in a dose-dependent relationship when cells
      were exposed to CH and CSS simultaneously for 1 hour. The expression of p21
      increased significantly when cells were exposed to CH for 24 hours, but there was
      no significant increase when cells were exposed to CSS for 24 hours. However,
      there was an additive effect on the expression of p21 when cells were exposed to
      CH and CSS simultaneously for 24 hours. When cells were exposed to CH and CSS
      simultaneously three times (24 hours each time), then passaged for 1 month, the
      expression of p21 increased synergistically. In conclusion, DNA damage and
      activation of c-ras may be involved in the process of combined carcinogenesis of
      CH and CSS.

PMID- 10905504
TI  - Effect of endothelin-1 on the biological changes of the corpus luteum regression
      process.
AB  - The present study was conducted to evaluate whether apoptosis occurs during the
      corpus luteum (CL) regression process in rats, and, if so, to determine the
      effect of endothelin-1 (ET-1) in this process. In order to obtain CL cells,
      immature female rats were treated with pregnant mare serum gonadotropin (PMSG)
      and human chorionic gonadotropin (hCG) to cause hyperovulation. CL cells were
      treated with three different dosages of ET-1 (1.0 x 10(-5) M, 1.0 x 10(-7) M, and
      1.0 x 10(-9) M). The occurrence of apoptosis, intracellular calcium
      concentrations, and progesterone production were measured to determine the
      biological changes in the CL cells. We found that apoptosis occurs during CL
      regression accompanied by an increase in intracellular calcium, while
      progesterone production was decreased. ET-1 promotes the apoptosis through an
      increase in the intracellular calcium in the CL cells and affects the
      physiological function of CL cells by inhibiting progesterone production. ET-1
      was shown to be an important regulator of CL during its regression.

PMID- 10905505
TI  - Cryptorchidism induces mouse testicular germ cell apoptosis and changes in bcl-2
      and bax protein expression.
AB  - Up to half of the germ cells die during their development. The mechanism involved
      in their death is still unclear. We investigated the possibility that the
      testicular germ cell loss may be due to a change in the testicular temperature
      and apoptosis through the interplay of bcl-2 and bax proteins. To investigate the
      effect of temperature on apoptosis and the role of bcl-2 and bax proteins in
      apoptosis in adult mouse testis, we used the experimental unilateral
      cryptorchidism model. We found that the weight of the affected testis decreases
      in 6 to 15 days after operation (p < 0.05). H&E staining showed vacuolization of
      the seminiferous epithelium and the appearance of multinucleated giant cells with
      loss of germ cells. The terminal deoxynucleotidyl transferase-mediated dUTP nick
      end-labeling method (TUNEL) showed positive staining germ cells scattered in
      normal testicles that increased significantly 6 to 15 days after experimental
      cryptorchidism (p < 0.05). Positive cells were mainly primary spermatocytes and
      round spermatids. DNA ladder was seen in 1.5% agarose gel electrophoresis in 6 to
      15 days-operated testicles. Biotin-avidin DCS system indirect immunofluorescence
      technique indicated that the bcl-2 protein was chiefly distributed in the
      cytoplasm of germ cells in normal testicles, whereas the bax protein was chiefly
      expressed in the cytoplasm of germ cells in 6 to 15 days-operated testicles.
      Western blot analysis showed that the bcl-2 protein down-regulated and the bax
      protein up-regulated apoptosis. Our data indicated that cryptorchidism-induced
      testicular cell degeneration was mediated by apoptosis probably as the result of
      increased temperature in the testicle; bcl-2 and bax proteins played important
      roles in male germ cell apoptosis.

PMID- 10905506
TI  - Mutagenicity of methyl tertiary butyl ether.
AB  - Methyl tertiary butyl ether (MTBE), the main component of oxygenated gasoline, is
      added to gasoline as an octane enhancer to reduce automotive emissions. We
      evaluated the mutagenicity of domestic MTBE using the Ames test, unscheduled DNA
      synthesis (UDS) assay, and NIH/3T3 cell micronucleus test. MTBE did not show any
      mutagenic potential in the Ames assay (TA98, TA100 strains) with or without rat
      liver-derived metabolic activation system (S-9). In rat primary hepatocyte UDS
      assay, a dose-response relationship was observed, which meant that MTBE might
      damage normal DNA and induce unscheduled DNA synthesis. MTBE did not show
      positive results in the NIH/3T3 cell micronucleus test. It could be concluded
      that MTBE has some degree of mutagenicity.

PMID- 10905507
TI  - Effect of leaded and unleaded gasoline on the mutagenicity of vehicle exhaust
      particulate matter.
AB  - With the removal of lead from gasoline and the use of new technologies, there
      have been some changes in vehicle emissions. In order to find out if the unleaded
      gasoline has the ability to reduce the emission of pollutants, leaded and
      unleaded gasoline were tested on a Santana engine dynamometer under a standard
      test cycle. The concentrations of hydrocarbons (HC) and carbon monoxide (CO) in
      emission were analyzed. The extracts of total exhaust particles were also
      collected and the components were detected by gas chromatography/mass
      spectrometry (GC/MS). A series of different end point genotoxicity tests,
      including the Ames test, the single cell gel electrophoresis (SCGE) assay, and
      micronucleus induction assay, were performed to investigate the mutagenicity in
      the two kinds of gasoline. We found that unleaded gasoline could reduce the
      emission of CO and HC and significantly decrease the quantity of vehicle exhaust
      particulate matter by 60%. As for the component analysis, only 23 kinds of
      organic substances adsorbed onto the particles were identified in the unleaded
      gasoline, while 32 kinds of compounds were detected in the leaded gasoline. The
      genotoxicity tests indicated that both types of gasoline could enhance the number
      of histidine-independent colonies in the Ames test, cause DNA damage, and
      increase the frequency of induced micronucleus in the Chinese hamster lung (CHL)
      cells. For the same particle weight, no difference was found between their
      mutagenicity. Because of the decrease in the emission of CO, HC, and particles in
      unleaded gasoline, this gasoline has some benefits for the environment and human
      health.

PMID- 10905508
TI  - Role of molecular oxygen in the generation of hydroxyl and superoxide anion
      radicals during enzymatic Cr(VI) reduction and its implication to Cr(VI)-induced
      carcinogenesis.
AB  - Electron spin resonance (ESR) spin trapping measurements provide evidence for the
      generation of hydroxyl radicals (*OH) in the reduction of Cr(VI) by glutathione
      reductase (GSSG-R) in the presence of NADPH as a cofactor. Catalase inhibited the
      *OH generation, while the addition of H2O2 enhanced it, indicating that the *OH
      radical generation involves a Fenton-like reaction. The metal chelator,
      deferoxamine, inhibited the *OH generation with a concomitant generation of a
      deferoxamine nitroxide radical. EDTA and 1,10-phenanthroline also inhibited the
      *OH generation. Experiments performed under argon atmosphere decreased the yield
      of the *OH formation, showing that molecular oxygen plays a critical role. ESR
      spin trapping and measurements of fluorescence change of scopoletin in the
      presence of horseradish peroxidase show that reduction of Cr(VI) by GSSG-R/NADPH
      generates superoxide anion radicals (O2*-) as well as H2O2. It can be concluded
      that *OH radical is generated by the reaction of H2O2 with Cr(V), which is
      produced by enzymatic one-electron reduction of Cr(VI). H2O2 is produced by the
      reduction of molecular oxygen via O2*- as an intermediate. The *OH radicals
      generated by these reactions are capable of causing DNA strand breaks, which can
      be inhibited by catalase, formate, and experiments performed under argon.

PMID- 10905509
TI  - Antineoplastic effect of intracellular expression of a single-chain antibody
      directed against type IV collagenase.
AB  - It has been shown that the type IV collagenase with its two subtypes, 72 kDa/ MMP
      2 and 92 kDa/MMP-9, plays an important role in tumor invasion and metastasis
      formation that occur through a mechanism of proteolytic degradation of collagen
      IV in the basement membrane. One possible method to specifically inhibit the
      function of the targeted protein of a cell is to express intracellular antibody
      combining site that can block the function or prevent the expression of the
      targeted molecule. Accordingly, intracellular antibodies against type IV
      collagenase may have a therapeutic use against tumor invasion and metastasis. As
      described in our previous reports, an anti-type IV collagenase monoclonal
      antibody (3D6) was obtained using the hybridoma approach, and its functional
      single-chain Fv fragment (scFv) named M97 was constructed based on recombinant
      phage display techniques. In this study, the endoplasmic reticulum (ER)-retained
      scFv antibody fragment was used to inhibit the function of type IV collagenase.
      For expression in mammalian cells, the assembled scFv M97 gene with ER retention
      signal encoding 6 additional amino acid (SEKDEL) was reamplified by PCR. The
      amplified fragments were cloned into the pcDNA3.1 vector containing the CMV early
      intermediate promoter/enhancer. The resulting plasmid was sequenced and then
      introduced by the lipofectamine method into PG cells, a highly metastatic human
      lung cancer cell line and G418-resistant cells were obtained by G418 selection.
      After transfection, the M97 mRNA expression was observed and the type IV
      collagenase expression was downregulated significantly as measured by ELISA. The
      biological behavior of PG cells, such as the ability of in vitro invasion of
      colony formation on soft agar through Matrigel, were also inhibited by scFv M97
      transfection. The results indicate that intracellular antibody technology
      represents a novel and efficient way to selectively abrogate the activity of type
      IV collagenase, at least in vitro. We are presently exploring the efficacy of
      this approach in a xenograft model of human lung cancer.

PMID- 10905510
TI  - Potentiation of BCNU anticancer activity by O6-benzylguanine: a study in vitro
      and in vivo.
AB  - O6-Alkylguanine-DNA alkyltransferase (O6-AGT), a constitutively expressed DNA
      repair protein, removes alkyl groups from the O6-position of guanine in DNA.
      Tumor cells with high O6-AGT activity are resistant to nitrosoureas and other
      agents that form toxic O6-alkyl adducts. We evaluated O6-benzylguanine (O6-BG)
      for its activity to inhibit O6-AGT and potentiate 1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU) in O6-AGT-positive human gastric adenocarcinoma cell line, BGC
      823 and its tumor xenograft. The sensitivity of BGC-823 cells to BCNU was
      increased by pretreatment for 2 hours with 1.5 to 6.0 microg/mL O6-benzylguanine.
      O6-benzylguanine (0.75-6.0 microg/mL) completely and rapidly suppressed the O6
      AGT activity of cells for up to 12 hours. When given i.p. 2 hours before BCNU (25
      mg/kg) to animals bearing s.c. tumors, O6-BG (90 mg/kg) produced a growth delay
      of 38.6 days in human gastric adenocarcinoma xenograft. Furthermore, O6-BG
      significantly inhibited the O6-AGT activity of tumor tissue and induced evident
      apoptosis. These results suggest that combination of O6-BG with BCNU may have a
      significant therapeutic effect in the treatment of mer + tumor.

PMID- 10905511
TI  - Therapeutic drug monitoring of paclitaxel (Zisu) in cancer patients.
AB  - We monitored the therapeutic drug paclitaxel (Zisu) and studied its anticancer
      activity and side effects in 11 cancer patients. After intravenous infusion of
      135 to 185 mg/m2 of paclitaxel, Cmax ranged from 2.17 to 9.17 mg/L and AUC ranged
      from 4.37 to 16.01 mg/h/L. A significant individual difference in pharmacokinetic
      parameters was found. Among the 11 patients, 6 achieved a partial remission and
      one patient had a mild response. The Cmax of the patients who achieved PR and MR
      was higher in comparison to the patients with no response. In 4 of the 6 PR
      patients, Cmax was above 4.38 mg/L. In four of the NR patients, Cmax was equal to
      or below 4.04 mg/L. These results suggested a relationship between Cmax and the
      cancer response rate. No significant relationship could be found between Cmax and
      the nadir of the white blood cells and platelets.

PMID- 10905512
TI  - Effect of dietary fatty acids on tumorigenesis of colon cancer induced by methyl
      nitrosourea in rats.
AB  - We studied the effect of dietary fatty acid composition on the tumorigenesis of
      colon cancer induced by methyl nitrosourea (MNU) in rats. Five groups of Sprague
      Dawley male rats were fed with semi-synthetic diets that contained different
      proportions of beef tallow, soybean oil, alkana oil, corn oil, and fish oil for
      180 days. Each group was matched with a control group fed with the same diet. The
      experimental groups were given MNU in PBS i.p. 6 times at weekly intervals. The
      control groups were given PBS only. The incidence of colon cancer, the average
      volume of the tumors, PCNA, cell kinetics, membrane lipid fluidity, ALP activity,
      and the content of PGE2 in colonic mucous and the fatty acid distribution in the
      testis pad fat were measured at the end of the experiment. The results showed
      that the incidence of colon cancer and the average volume of the tumors in
      animals fed with diets that contained mainly beef tallow, soybean oil, or alkana
      oil were significantly higher than that in animals fed with diets that contained
      mainly fish oil. The diet containing 13.9% of SFA, 16.4% of MUFA, and 68.8% of
      PUFA showed the strongest inhibition effect. This may be due to the mechanism of
      protecting the membrane lipid fluidity, decreasing the amount of PCNA in colon
      cells, the number of propidium iodine-labeled cells in S phase, the activity of
      ALP and inhibiting the production of AA and thus decreasing the amount of PGE2.

PMID- 10905513
TI  - Plasma and tissue concentrations of beta-carotene and vitamin A in rats fed beta
      carotene in various fats of plant and animal origin.
AB  - We investigated the effects of various types of dietary fat of plant and animal
      origin on beta-carotene absorption and tissue accumulation in rats. Rats were fed
      1 mL of butter fat, lard, tallow, sunflower, arachidonic, soya, olive, or linseed
      oil containing 175 mg beta-carotene/mL fat by gavage, twice a week for 4 weeks.
      The beta-carotene and vitamin A levels in plasma and tissues were determined by
      rp-HPLC. The highest levels of absorbed beta-carotene were observed in the liver
      of animals fed olive and arachidonic oil (p < 0.001), and in the lungs of animals
      fed sunflower oil. Histomorphological studies showed that the observed highly
      variable accumulation of beta-carotene in lung tissue was most probably due to an
      endogenously caused lipid pneumonia. No beta-carotene was observed in blood
      plasma, kidney, and spleen in any group. Plasma vitamin A levels (retinol) were
      increased with tallow, olive, and arachidonic oil (p < 0.05). The most obvious
      influence was found for vitamin A in the spleen. Levels in rats fed tallow (p <
      0.05), butter, or lard (p < 0.001) were higher than in controls. The lowest
      vitamin A levels were found in rats fed fat of plant origin. Our results suggest
      that the type of dietary fat can modulate the absorption of beta-carotene as well
      as the distribution of vitamin A in plasma and selected tissues.

PMID- 10905514
TI  - Expression of metallothionein in invasive ductal breast cancer in relation to
      prognosis.
AB  - The aim of this study was to assess the presence and clinical significance of
      metallothionein (MT) in primary invasive ductal carcinoma of the breast. We
      investigated 96 cases of routinely fixed and paraffin-embedded primary breast
      carcinomas with the immunohistochemical method. Positive staining for MT was
      observed in 52.1% of specimen. In most cases both nuclear and cytoplasmic
      staining was seen. A statistically significant association was found between MT
      positive staining and nuclear grade (p < 0.01). MT-positive cases had a
      significantly poorer prognosis when compared with the MT-negative cases (p <
      0.01). We concluded that the MT expression may be of a prognostic value for
      primary invasive ductal carcinoma of the breast and is possibly an indicator of
      more aggressive and less differentiated carcinoma cells.

PMID- 10905515
TI  - Dust exposure and lung cancer mortality in tunnel workers.
AB  - The eastern part of the Toyama Prefecture in Japan is one of the high-incidence
      areas of silicosis due to tunnel construction. In 1977 and 1978, we conducted a
      questionnaire survey primarily concerning the occupational history of all male
      inhabitants over 30 years of age living in five villages in this area and found
      603 tunnel workers and inhabitants without dust history. These workers have been
      followed up to 1994 for about 17 to 18 years to clarify the relationship between
      tunnel work and lung cancer mortality. The SMR's of workers with dust exposure
      for all causes and for lung cancer was 120 and 188, respectively, which was
      significantly higher than those of the Japanese general population. After
      adjustment for age and smoking habits using Cox's proportional hazard model,
      tunnel work showed a significant relationship to mortality. Mortality risk ratio
      of tunnel workers was 2.15 compared with that of inhabitants without dust
      exposure history.

PMID- 10905516
TI  - Cytogenetic damage and cell-mediated immunity in pneumoconiosis.
AB  - The International Agency for Research on Cancer (IARC) determined that
      crystalline silica inhaled from occupational sources should be classified as
      carcinogenic to humans and upgraded it from group 2A to group 1. It has also been
      found that silicosis may be associated with cancer of various organs and with
      autoimmune diseases. We studied both the cytogenetic effects and the influence on
      cell-mediated immunity of mineral dust inhalation in patients with
      pneumoconiosis, including silicosis. The frequency of sister chromatid exchanges
      and micronucleus in the pneumoconiosis group were significantly higher than in
      the controls, suggesting a cytogenetic influence of the occupationally inhaled
      dust. Alterations in the immunoregulatory T cells were observed in the
      pneumoconiosis groups, suggesting that inhaled mineral dust may cause immunotoxic
      effects. Based on these findings, we can consider that cytogenetic damages and
      immunoregulatory abnormalities in pneumoconiosis patients may play a role in the
      pathogenesis of various cancers and autoimmune diseases associated with
      pneumoconiosis.

PMID- 10905517
TI  - Mineral dust exposure and systemic diseases.
AB  - Based on clinical and immunological studies, we have proposed the hypothesis that
      occupational dust exposure might cause not only pneumoconiosis but also
      autoimmune diseases and malignancies of various organs such as neoplasms of
      lymphatic and hematopoietic tissues and gastric cancer. Evidence from cohort
      studies of pneumoconiotic patients in Japan, copper miners, and stone masons
      support our hypothesis. The carcinogenicity and cytotoxic effect of inhaled dust
      on immune cells are considered to contribute to the development of these
      diseases.

PMID- 10905518
TI  - Predisposing factors in occupational lung cancer: inorganic minerals and
      chromium.
AB  - Reactive oxygen species (ROS) have been implicated in the pathogenesis of cancer.
      Inhalation of inorganic minerals such as asbestos and crystalline silica, and
      metals such as arsenic, beryllium, chromium, nickel, and vanadium, may promote
      directly and indirectly enhanced generation of ROS at a persistent level in
      concert with chronic inflammation. Perpetual ROS generation can cause specific
      molecular changes resulting in the activation or inactivation of transcription
      factors that may alter gene expression leading to cell proliferation,
      differentiation, and carcinogenesis. The mechanisms involved in the signal
      transduction leading to these processes are the subject of intense investigation.
      In this review, some of the recent findings from our laboratories concerning key
      molecular events elicited by asbestos, crystalline silica, and chromium are
      presented. These include genotoxicity, DNA damage, lipid peroxidation, activation
      of transcription factors activator protein-1 (AP-1) or nuclear factor kappa B (NF
      kappaB), and p53 or k-ras gene alterations. From these studies, it is evident
      that ROS signaling is critical for the responses of cytokines, growth factors,
      and activation or inactivation of transcription factors that promote
      carcinogenesis.

PMID- 10905519
TI  - The fumonisin B1 content in corn from North China, a high-risk area of esophageal
      cancer.
AB  - Fusarium moniliforme is the primary fungus contaminating corn throughout the
      world. Fumonisin B1 (FB1) is the major metabolite of F. moniliforme. It has been
      shown that FB1 is the promoter and initiator of liver cancer in rat. The corn of
      Cixian, in Hebei Province, the high-risk area for esophageal cancer in China, is
      often contaminated by this fungus. A total of 21 corn samples were collected from
      households in the Cixian County. High levels of FB1 (88.90+/-13.1 microg/g) were
      found in 10 moldy samples, and low levels (1.40+/-0.50 microg/g) of FB1 were
      found in 11 apparently healthy corn samples. The positive detection rates of FB1
      in moldy and normal samples were 100 and 90.9%, respectively. The frequency of
      FB1 contamination in the high-risk area is about twice that in the low-risk
      areas, and the average content of FB1 in samples from high-risk areas was
      approximately three times that from low-risk areas. Our data indicate that FB1
      contaminated corn may be involved in the carcinogenesis of esophageal cancer in
      high-risk areas of North China.

PMID- 10905520
TI  - A case-control analysis of leukemia in accident emergency workers of Chernobyl.
AB  - We estimated the radiation-induced risk of leukemia in 162,684 Chernobyl accident
      emergency workers (EWs) using the data of the Russian National Medical and
      Dosimetric Registry (RNMDR). A system was established for the collection and
      verification of data in 55 cases of leukemia from 1986 to 1995. The principal
      analysis included 41 leukemia cases that occurred more than 2 years after the
      first exposure to radiation. The case-control methodology was used to evaluate
      the risk of leukemia associated with various factors. Radiation dose, effective
      exposure dose rate, date of entry into the Chernobyl zone (ChZ), and the duration
      of stay in the zone were used as risk factors. The relationship between the date
      of entry and the duration of stay in the zone was investigated. All cases of
      leukemia, excluding chronic lymphocytic leukemia (CLL), were analyzed. An
      analysis was also performed on all EWs and on the EWs who worked in the zone from
      1986 to 1987 (EWs of 1986 to 1987). No significant association was found between
      the risk of leukemia and the factors we investigated. Nevertheless, the relative
      risk estimates for leukemia, excluding CLL, were greater than the value for all
      leukemia and were greater than one. The estimated excess relative risk (ERR) per
      Gy was greater for all EWs [ERR = 1.33, 95% confidence interval (CI): -6.25, 8.90
      for all leukemia, and ERR = 15.59, 95% CI: -24.92, 56.11 for leukemia, excluding
      CLL] compared with EWs of 1986 to 1987 (ERR = 0.28, 95% CI: -5.84, 7.41 for all
      leukemia, and ERR = 9.43, 95% CI: -20.0, 38.86 for leukemia, excluding CLL).

PMID- 10905521
TI  - The immunomarker of aging and the modulatory effect of Chinese medicinal herbs on
      the dysfunction of lymphocytes in the elderly.
AB  - PURPOSE: This study examined an immunomarker of aging and evaluated the
      modulatory effect of Chinese medicinal herbs (CMH) on the immune function of
      lymphocytes in the elderly. METHODS: Forty-seven elderly and fifteen young
      persons were selected as study subjects. Peripheral blood lymphocytes (PBL) were
      isolated by Ficoll-Hypaque gradient centrifugation. The responsive proliferation
      was investigated by means of the 3H-TdR incorporation procedure. The phenotype
      and receptor of lymphocytes were measured using indirect immunofluorescence.
      RESULTS: Both Rg1 and Gy-P significantly increased the responsive proliferation
      of lymphocytes in the elderly, p < 0.001 and p < 0.05, respectively. Rg1 also had
      a stimulatory effect on the receptor, CD25, and phenotype, CD45RA, CD45RO, in
      lymphocytes in aged persons. The immunomarker of aging was established by
      multiparametric indications on the basis of study at the cellular and molecular
      levels. CONCLUSION: The possibility exists that a lowered immune function can be
      reversed with modulation. In the near future, a highly purified, nontoxic, and
      more effective immunomodulator could be produced from CMH as an antiaging drug.

PMID- 10905522
TI  - Follow-up of elderly diabetics with or without hypertension and hyperlipidemia.
AB  - Elderly diabetic patients were followed up prospectively for 4 years to see the
      effects of blood pressure and dyslipidemia on the development of diabetic micro-
      and macroangiopathies. We studied 84 elderly diabetic patients whom we divided
      into four groups according to the association of above complications: (1)
      diabetes alone group (DM), (2) hypertensive diabetic group (DM + HT), (3)
      hyperlipidemic diabetic group (DM + HL), and (4) hypertensive and hyperlipidemic
      diabetic group (DM + HTL). The treatment of diabetes was different among the
      groups. Glycemic control such as fasting blood glucose and HbA1c did not change
      between groups or through the follow-up years. As a matter of course, blood
      pressure of DM was lower and triglyceride of HTL was higher than in other groups.
      Microangiopathies such as retinopathy, nephropathy, and neuropathy and
      macroangiopathies such as ischemic heart disease (IHD), cerebral vascular disease
      (CVD), and arteriosclerosis obliterans were evaluated by using a grading scale
      according to the severity. The grade of microangiopathies in DM + HT increased
      gradually during the follow-up years and the grade of IHD and CVD in DM + HTL was
      relatively higher than in the other groups. Our findings support the general
      principle of control of hypertension and hyperlipidemia for the prevention of
      diabetic microangiopathy and macroangiopathy in the elderly diabetic patients.

PMID- 10905523
TI  - Correlation between bone mineral density and sexual hormones in healthy Chinese
      women.
AB  - Osteoporosis is a common disease in women, but not in men. It is usually induced
      by the deficiency of estrogen after menopause. The lumbar spine is most often
      affected. We examined 74 healthy Chinese women in whom we measured serum
      estradiol (E2), estriol (E3), and total testosterone (TTT) by radioimmunoassay
      (RIA). The bone mineral density (BMD) of the total lumbar spine in the anterior
      (TLS-A) and lateral (TLS-L) position, the region of interest (ROI) of lateral
      spine (M-IALS), the forearm, and the total hip (TH) were scanned by a dual-energy
      X-ray absorptiometer. We found that (1) E2 and all BMD determinations declined
      significantly after menopause (p < 0.05 for all), except the BMD of TH; (2) the
      BMD of TLS-L, TH, and forearm correlated significantly with E2 (r = 0.2986, p <
      0.05), E3 (r = 0.3380, p < 0.05), and TTT (r = 0.2867, p < 0.05), respectively,
      by partial correlation analysis. In conclusion, BMD at different sites of the
      skeleton correlated with the level of different sex hormones. It seems that BMD
      at different sites of the body is controlled by different sex hormones. Whether
      this phenomenon should be considered in the choice of hormone replacement
      therapy, or in improving the BMD diagnostic standard, needs further study.

PMID- 10905524
TI  - Linking environmental cancer with occupational epidemiology research: the role of
      the International Agency for Research on Cancer (IARC).
AB  - BACKGROUND: The International Agency for Research on Cancer (IARC) provides the
      most credible assessment of carcinogenicity for the scientific community. IARC
      Monographs also suggest areas where new laboratory and epidemiology research on
      cancer should be focused. REVIEW: This presentation examines two recent IARC
      reports on silica and coal dust (from 1997), and on occupational exposures to
      insecticide and pesticide applications (from 1991). RESULTS: From the Silica
      Monograph, the research implications suggest that laboratory and epidemiology
      studies would be useful focusing on mixtures of hazards where silica is a
      significant component of the respirable environment: in coal mining (which has an
      excess of gastric cancers) with variations in silica exposure; in uranium mining
      where there is silica dust plus radon decay products, in foundries and steel
      making plants where silica exposure is common as are other carcinogenic hazards;
      in agriculture where dusty farming may be common, and comparisons are needed with
      other polymorphs of silica, including amorphous quartz. Additional studies of
      lymphatic, dermal, and gastrointestinal malignancies are needed to determine if
      the evidence of silicocarcinogenesis extends to these tumor sites. Finally, some
      fundamental studies of adsorptive capability of silica and resultant biologic
      activity, including biomarker studies, are needed. In the pesticide realm, there
      are many active ingredients that have been shown to be 2B (or possible)
      carcinogens based on animal studies (or other evidence). Industrial epidemiology
      studies of workers manufacturing or handling chemicals such as atrazine,
      chlordane, dichlorvos, 2,4-D, and DDT should be undertaken. Cancer epidemiology
      associations have been demonstrated for chemicals such as phenoxy acid
      herbicides, 2,4,5-T, lindane, methoxychlor, toxaphene, and several
      organophosphate insecticides for which laboratory studies are needed.
      CONCLUSIONS: IARC reviews offer many leads for future research and insightful
      protocols that can provide new leads for studying these common exposures under
      novel environmental conditions.

PMID- 10905525
TI  - Case-control differences in the reliability of reporting a history of induced
      abortion.
AB  - The authors investigated the possibility that, in interview-based case-control
      studies, controls are more likely than cases to underreport a history of induced
      abortion. A case-control study was conducted in White women under 45 years of age
      who had given birth in Washington State during 1984-1994. The cases were women in
      three metropolitan counties of Washington State diagnosed with invasive breast
      cancer during 1984-1994; controls were selected through random digit dialing. A
      history of induced abortion among study participants was compared between
      interview data and information collected on the birth record of the last child to
      whom they gave birth (225 cases, 303 controls). Among women with a prior induced
      abortion recorded on the birth record, 14.0% of the 43 cases and 14.9% of the 47
      controls did not report an induced abortion at interview (difference = -0.9%, 95%
      confidence interval of the difference: -15, 14). The authors' data do not suggest
      that controls are more reluctant to report a history of induced abortion than are
      women with breast cancer.

PMID- 10905526
TI  - Reporting bias in case-control studies on induced abortion and breast cancer.

PMID- 10905527
TI  - Cervical neoplasia and repeated positivity of human papillomavirus infection in
      human immunodeficiency virus-seropositive and -seronegative women.
AB  - Increased risk for cervical intraepithelial neoplasia (CIN) in human
      immunodeficiency virus (HIV)-infected women may be explained by repeated
      positivity of human papillomavirus (HPV) infection facilitated by HIV infection
      and related immunosuppression. As part of a longitudinal study with semiannual
      examinations, 268 women in Baltimore, Maryland (of whom 184 were HIV+), provided
      1,426 cervicovaginal lavage specimens tested for HPV DNA by a polymerase chain
      reaction-based assay between 1992 and 1998. HPV positivity and time to HPV
      clearance according to HIV serostatus and CD4+ cell count were compared using
      models for correlated binary data and survival analysis. Of the 187 participants
      who had at least one positive measurement, the probability of subsequent HPV
      positivity among HIV- women and HIV+ women with CD4+ > or =200 and <200
      cells/microl was 47.5%, 78.7%, and 92.9% (p < 0.001). Within-women HPV results
      were correlated (i.e., clustered) in each group (p < 0.01). Compared with HIV
      participants, the relative incidence of HPV clearance was 0.29 and 0.10 among
      HIV+ women with CD4+ > or =200 and <200 cells/microl (p < 0.001). At the end of
      follow-up, 11 women had biopsy-confirmed CIN. The association of HIV and CIN (p =
      0.014) was fully explained by repeated HPV positivity induced by HIV infection (p
      = 0.648). Reversal of immunosuppression following potent antiretroviral therapy
      must be expected to have a dramatic impact on HIV-related CIN.

PMID- 10905528
TI  - Mathematical model for the natural history of human papillomavirus infection and
      cervical carcinogenesis.
AB  - The authors constructed a Markov model as part of a systematic review of cervical
      cytology conducted at the Duke University Evidence-based Practice Center (Durham,
      North Carolina) between October 1997 and September 1998. The model incorporated
      states for human papillomavirus infection (HPV), low- and high-grade squamous
      intraepithelial lesions, and cervical cancer stages I-IV to simulate the natural
      history of HPV infection in a cohort of women from ages 15 to 85 years. The age
      specific incidence rate of HPV, and regression and progression rates of HPV and
      squamous intraepithelial lesions, were obtained from the literature. The effects
      of varying natural history parameters on cervical cancer incidence were evaluated
      by using sensitivity analysis. The base-case model resulted in a lifetime
      cervical cancer risk of 3.67% and a lifetime cervical cancer mortality risk of
      1.26%, with a peak incidence of 81/100,000 at age 50 years. Age-specific
      distributions of precursors were similar to reported data. Lifetime risk of
      cancer was most sensitive to the incidence of HPV and the probability of rapid
      HPV progression to high-grade lesions (two- to threefold variations in risk). The
      model approximates the age-specific incidence of cervical cancer and provides a
      tool for evaluating the natural history of HPV infection and cervical cancer
      carcinogenesis as well as the effectiveness and cost-effectiveness of primary and
      secondary prevention strategies.

PMID- 10905529
TI  - Weight gain continues in the 1990s: 10-year trends in weight and overweight from
      the CARDIA study. Coronary Artery Risk Development in Young Adults.
AB  - The prevalence of obesity increased in the United States through the 1980s. The
      authors examined 10-year aging and secular (time-related) trends in the Coronary
      Artery Risk Development in Young Adults (CARDIA) cohort for indications of
      whether these trends are continuing and for ages of peak weight gain in young
      adults. CARDIA is a population-based, prospective study of 5,115 African-American
      and White men and women aged 18-30 years at baseline. Body weight and overweight
      prevalence were measured at five time points from 1985-1986 to 1995-1996. Linear,
      mixed-model regression was used to partition weight gain into that due to secular
      trends and that due to aging. Prevalence of overweight (body mass index (BMI) >
      or = 25.0 kg/m2) increased markedly, and prevalence of severe obesity (BMI > or =
      40.0 kg/m2) doubled in all race-sex groups. Each race-sex group experienced
      significant secular weight gains, ranging from 0.96 kg/year (95% confidence
      interval: 79, 1.13) in African-American women to 0.55 kg/year (95% confidence
      interval: 0.41, 0.69) in White women. Significant secular gains were present
      during each follow-up period. Each race-sex group also experienced significant
      weight increases related to aging during their early to midtwenties. Secular
      trends for weight gain are continuing in CARDIA, but the magnitude of weight gain
      differed among the four race-sex groups.

PMID- 10905530
TI  - Serum copper concentration and coronary heart disease among US adults.
AB  - Copper, a strong prooxidant, may play a role in atherogenesis. The author
      examined the association between serum copper concentration and mortality from
      coronary heart disease using data from the Second National Health and Nutrition
      Examination Survey (1976-1992). Serum copper concentration was determined using
      atomic absorption spectroscopy. After various exclusions, 151 deaths from
      coronary heart disease occurred among 4,574 participants aged > or =30 years. At
      baseline, the age-adjusted serum copper concentration was about 5% higher among
      participants who died from coronary heart disease than among those who did not (p
      = 0.072). After adjustment for age, sex, race, education, smoking status,
      systolic blood pressure, serum cholesterol, serum high density lipoprotein
      cholesterol, body mass index, recreational activity, nonrecreational activity,
      history of diabetes, and white blood cell count, the hazard ratios for death from
      coronary heart disease for serum copper concentrations in the second, third, and
      fourth quartiles (versus the first quartile) were 1.84 (95% confidence interval
      (CI): 0.93, 3.66), 2.14 (95% CI: 1.21, 3.77), and 2.87 (95% CI: 1.57, 5.25),
      respectively. Several prospective studies, including the present analysis, have
      found elevated serum copper concentrations to be associated with cardiovascular
      disease. Whether copper directly affects atherogenesis or is a marker of
      inflammation associated with atherosclerosis remains to be established.

PMID- 10905531
TI  - Is the apparent cardioprotective effect of recent alcohol consumption due to
      confounding by prodromal symptoms?
AB  - Previous research has reported a protective association between alcohol drinking
      and acute coronary heart disease in the 24-hour period after drinking. This study
      investigated whether this apparent protective association resulted from
      confounding due to the effect of prodromal symptoms on drinking behavior. In
      1992, the authors conducted a case-control study that measured recent alcohol
      consumption and reasons for recent abstention from alcohol among patients with
      acute coronary heart disease identified from a community-based disease register
      and a representative control sample from the same community (Auckland, New
      Zealand). Cases were significantly more likely than controls to report recent
      abstention from drinking because they felt unwell. In unadjusted analyses, a
      protective association was observed between recent alcohol consumption and acute
      coronary heart disease; however, this association was weakened considerably after
      adjustment for the effect of prodromal symptoms on drinking behavior. The
      previously reported protective association between recent alcohol consumption and
      acute coronary heart disease appears to be largely due to the confounding effect
      of prodromal symptoms on drinking.

PMID- 10905533
TI  - Model for the analysis of binary time series of respiratory symptoms.
AB  - Environmental epidemiologic research on respiratory symptoms presents unique
      types of data, typically requiring simultaneous analysis of both time- and person
      varying factors. In this paper, the authors propose a new, simple model that
      incorporates such factors and controls for each person's prior history of
      symptoms. The Yale Mother and Infant Health Study was undertaken to investigate
      the effects of ambient pollutant concentrations, meteorologic changes, and
      demographic variables on daily respiratory symptoms in both mothers and infants.
      This analysis was restricted to 673 mothers followed in southwestern Virginia
      from June 10 to August 31, 1995. Of the person-varying factors, husband's level
      of education, nested within marital status, and having pets in the home were
      related to an increased likelihood of new episodes; however, neither was related
      to duration of symptoms. Interestingly, women who were unmarried were least
      likely to have new episodes of respiratory symptoms, while those with the most
      highly educated spouses were most likely to have new episodes. Having pets in the
      home increased the likelihood of a new episode. Having a history of allergies and
      having children in day care were found to be related to the symptom of a runny or
      stuffy nose, in terms of both incidence and duration. The level of coarse
      particles was related to the incidence of new episodes of runny or stuffy nose,
      and a higher level prolonged the duration of symptoms. Sulfate level was not
      related to the incidence of new episodes but was associated with the duration of
      the episodes.

PMID- 10905532
TI  - Risk factors for second urinary tract infection among college women.
AB  - To better understand the etiology of recurrent urinary tract infection (UTI), the
      authors followed a cohort of 285 female college students with first UTI for 6
      months or until second UTI. A first UTI due to Escherichia coli was followed by a
      second UTI three times more often than was a non-E. coli first UTI (24 vs. 8%; p
      = 0.02). In a logistic regression analysis limited to the 224 women from the
      University of Michigan Health Service and the University of Texas at Austin
      Health Service from September 1992 to December 1994, with a first UTI due to E.
      coli, vaginal intercourse increased the risk of a second UTI with both a
      different (odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.19, 2.15) and
      the same (OR = 1.37, 95% CI: 0.91, 2.07) uropathogen, as did using a diaphragm,
      cervical cap, and/or spermicide (same uropathogen: OR = 1.53, 95% CI: 0.95, 2.47;
      different uropathogen: OR = 1.77, 95% CI: 1.22, 2.58). Condom use decreased the
      risk of a second UTI caused by a different uropathogen (OR = 0.68, 95% CI: 0.48,
      0.99) but had no effect on a second UTI caused by the same E. coli (OR = 0.99;
      95% CI: 0.66, 1.50). Type or duration of treatment was not associated with a
      second UTI. Although the risk of second UTI is strongly influenced by sexual
      behavior, women with a first UTI caused by E. coli are more likely than are those
      with a non-E. coli first UTI to have a second UTI within 6 months.

PMID- 10905534
TI  - Reproducibility of the University of Toronto self-administered questionnaire used
      to assess environmental sensitivity.
AB  - Environmental sensitivity patients report symptoms provoked by low-level exposure
      to a wide range of substances. Features of published case definitions include
      nature of onset, chronicity, symptom provocation by multiple substances, symptom
      provocation by an escalating number of exposures, involvement of multiple body
      systems including the nervous system, provocation by unrelated substances, and
      addictive behaviors. This study assessed the reproducibility of a Canadian self
      administered questionnaire, the University of Toronto Health Survey, designed to
      determine the prevalence of the features described in these case definitions. A
      total of 191 eligible respondents aged 16-70 years who attended several types of
      medical practices in 1994 were invited to complete a second questionnaire 5-7
      months after the first; 134 (70.2%) complied. Total agreement on whether patients
      satisfied each of seven case definitions ranged from 80% to 90%. After adjustment
      for chance, major agreement was observed for three of the seven case definitions
      (kappa = 0.69, 0.68, and 0.78). The survey achieved good reproducibility
      regarding self-report of symptoms described in published case definitions of
      environmental sensitivity.

PMID- 10905535
TI  - Out, out, brief candle! Oxidative stress response and life-span.

PMID- 10905536
TI  - Another jigsaw piece towards solving the iron metabolism puzzle: the cloning of
      the iron exporter, ferroportin1.

PMID- 10905537
TI  - Pretty in pink...

PMID- 10905538
TI  - Classic redox. Garrison WM, Jayko ME, Bennett W. Radiation-induced oxidation of
      protein in aqueous solution. Radiat Res 1962; 16: 483-502.

PMID- 10905539
TI  - Anti- and pro-oxidative properties of PADMA 28, a Tibetan herbal formulation.
AB  - There is growing public interest in traditional medicine. PADMA 28, a
      multicompound herbal preparation derived from Tibetan medicine, has proven
      efficacy in some clinical trials and tests at the cellular level. We report here
      on studies of PADMA 28 at the molecular level. Extracts of PADMA 28 contain both
      reducing and metal ion-chelating substances. In this way, PADMA 28 acts as a
      powerful antioxidant or prooxidant, depending on its concentration and the
      reaction under study.

PMID- 10905540
TI  - Increased oxidative stress in rats with chronic nitric oxide depletion:
      measurement of urinary 8-hydroxy-2'-deoxyguanosine excretion.
AB  - Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a
      sensitive biomarker of oxidative stress. We examined the effect of chronic
      blockade of nitric oxide (NO) on urinary excretion of 8-OHdG in rats. Two types
      of NO synthase inhibitor were used: N(G)-nitro-L-arginine methyl ester (L-NAME)
      as a non-selective inhibitor and aminoguanidine (AG) as a selective inhibitor of
      the inducible isoform. Oral administration of L-NAME (20, 50 and 80 mg/dl of
      drinking water), but not AG (400 mg/dl), for 4 weeks induced systemic
      hypertension and a significant reduction in urinary excretion of NO2-/NO3-. Rats
      treated with L-NAME also showed a significant increase in urinary 8-OHdG
      excretion compared with the control animals. The effects of L-NAME (50 mg/dl) on
      blood pressure and urinary excretion of NO2/NO3- and 8-OHdG were restored by a
      large dose of L-arginine (2.0 g/dl). Chronic AG administration did not
      significantly alter urinary 8-OHdG excretion. On combining all the data, there
      was a significant negative correlation between urinary NO2-/NO,- and 8-OHdG.
      These observations suggest the importance of constitutive NO synthase activity in
      the maintenance of oxidant buffering capacity in rats. Oral administration of L
      NAME may serve as a model of hypertension due to chronic NO deficiency with
      increased oxidative stress.

PMID- 10905541
TI  - Hydroxy-urea protects erythrocytes against oxidative damage.
AB  - Hydroxy-urea (OH-U) is used to treat sickle cell anemia by increasing hemoglobin
      fetal-fraction. It has been suggested that the sickle cell mutations lead to the
      formation of unstable HbS and release of iron, which can result in lipid
      peroxidation (LPO), and eventual cell damage. Since oxidative processes might be
      involved in pathogenesis of sickle cell disease, we investigated the antioxidant
      property of OH-U in a red blood cell (RBC) model. Intact RBCs or RBC membranes
      were exposed to t-butyl hydroperoxide (t-BHP, 0.75 mM) or iron (ferrous sulfate;
      100 microM) at 37 degrees C for 60 min in the presence or absence of OH-U (1.25
      mM). The extent of oxidative damage was measured by LPO (as thiobarbituric acid
      reactive substances, TBARS), hemoglobin oxidation (as percent of methemoglobin,
      metHb %), and decrease in the activities of membrane-bound Na+/K+-ATPase and Ca2+
      ATPases. Our results show that OH-U inhibited t-BHP-induced LPO in fresh RBC
      membranes significantly (P <0.01). OH-U significantly inhibited t-BHP-mediated
      LPO (P <0.01) and metHb formation (P <0.01) in intact RBC. Also, OH-U inhibited
      iron-induced LPO and metHb formation in intact RBC (P <0.01). In addition, OH-U
      blocked t-BHP-mediated changes in membrane ATPase activities. Furthermore, OH-U
      blocked iron-mediated hydroxyl radical generation in a dose-dependent fashion. In
      conclusion, the observed antioxidant properties of OH-U might contribute to its
      therapeutic action in sickle cell disease.

PMID- 10905542
TI  - Blood parameters indicative of oxidative stress are associated with symptom
      expression in chronic fatigue syndrome.
AB  - Full blood counts, ESR, CRP, haematinics and markers for oxidative stress were
      measured for 33 patients diagnosed with chronic fatigue syndrome (CFS) and 27 age
      and sex matched controls. All participants also completed symptom questionnaires.
      CFS patients had increases in malondialdehyde (P <0.006), methaemoglobin (P
      <0.02), mean erythrocyte volume (P <0.02) and 2,3-diphosphoglycerate (P <0.04)
      compared with controls. Multiple regression analysis found methaemoglobin to be
      the principal component that differentiated between CFS patients and control
      subjects. Methaemoglobin was found to be the major component associated with
      variation in symptom expression in CFS patients (R(2) = 0.99, P <0.00001), which
      included fatigue, musculoskeletal symptoms, pain and sleep disturbance. Variation
      in levels of malondialdehyde and 2,3-diphosphoglycerate were associated with
      variations in cognitive symptoms and sleep disturbance (R(2) = 0.99, P <0.00001).
      These data suggest that oxidative stress due to excess free radical formation is
      a contributor to the pathology of CFS and was associated with symptom
      presentation.

PMID- 10905543
TI  - Iron, alpha-tocopherol, oxidative damage and micronucleus formation in rat
      splenocytes.
AB  - The influence of low and high alpha-tocopherol diets in concert with a high
      polyunsaturated fat content and a modest increase in dietary iron has been
      studied. Iron supplementation at 5 times the recommended dietary level was not
      associated with any increased sensitivity of splenocytes to any of several
      oxidative challenges ex vivo. Despite the significantly higher alpha-tocopherol
      concentrations in plasma and liver in animals supplemented with this vitamin,
      there was no apparent protection against oxidative genotoxicity as judged by the
      formation of micronuclei in splenocytes subjected to oxidative stress ex vivo.
      These results add to the accumulating evidence that vitamin E supplementation has
      little effect against oxidative genomic damage, at least as demonstrated by an
      increase in micronucleus frequency.

PMID- 10905544
TI  - Effect of omega 3 fatty acids on oxidative stress in humans: GC-MS measurement of
      urinary F2-isoprostane excretion.
AB  - Despite the reported benefits associated with omega3 fatty acids for
      cardiovascular disease, there remains concern that increased intake may lead to
      increased lipid peroxidation. To date, however, the data, particularly in vivo,
      are inconclusive. This report describes two interventions, one providing daily
      fish meals and the other eicosapentaenoic acid (EPA, 20:5 omega3) or
      docosahexaenoic acid (DHA, 22:6 omega3), the two principal omega3 fatty acids in
      marine oils, in which in vivo lipid peroxidation was assessed by measurement of
      urinary excretion of F2-isoprostanes. In both trials, urinary F2-isoprostanes
      were significantly reduced by 20-27%. Therefore, in contrast with previous
      reports in the literature, these results demonstrate that omega3 fatty acids
      reduce in vivo oxidant stress in humans.

PMID- 10905545
TI  - The antihypertensive hydralazine is an efficient scavenger of acrolein.
AB  - Recent work indicates the highly toxic alpha,beta-unsaturated aldehyde acrolein
      is formed during the peroxidation of polyunsaturated lipids, raising the
      possibility that it functions as a 'toxicological second messenger' during
      oxidative cell injury. Acrolein reacts rapidly with proteins, forming adducts
      that retain carbonyl groups. Damage by this route may thus contribute to the
      burden of carbonylated proteins in tissues. This work evaluated several amine
      compounds with known aldehyde-scavenging properties for their ability to
      attenuate protein carbonylation by acrolein. The compounds tested were: (i) the
      glycoxidation inhibitors, aminoguanidine and carnosine; (ii) the
      antihypertensive, hydralazine; and (iii) the classic carbonyl reagent,
      methoxyamine. Each compound attenuated carbonylation of a model protein, bovine
      serum albumin, during reactions with acrolein at neutral pH and 37 degrees C.
      However, the most efficient agent was hydralazine, which strongly suppressed
      carbonylation under these conditions. Study of the rate of reaction between
      acrolein and the various amines in a protein-free buffered system buttressed
      these findings, since hydralazine reacted with acrolein at rates 2-3 times faster
      than its reaction with the other scavengers. Hydralazine also protected isolated
      mouse hepatocytes against cell killing by allyl alcohol, which undergoes in situ
      alcohol dehydrogenase-catalysed conversion to acrolein.

PMID- 10905546
TI  - Interactions between the UVA and UVB wavebands relevant for immune function and
      carcinogenesis.

PMID- 10905547
TI  - Control of thymocyte proliferation via redox-regulated expression of glycolytic
      genes.

PMID- 10905548
TI  - The dissection of oxidative changes in human blood serum and U937 cells exposed
      to free radicals.

PMID- 10905549
TI  - Hypochlorite-induced damage to red blood cells: evidence for the formation of
      nitrogen-centred radicals.

PMID- 10905550
TI  - Oxidation of 2,2,7,8-tetramethyl-6-chromanol, the model compound of gamma
      tocopherol, by hypochlorous acid.

PMID- 10905551
TI  - Inhibition of human immunodeficiency virus type 1 by packageable, multigenic
      antisense RNA.
AB  - Viral-based vectors can provide an efficient delivery mechanism for stable
      expression of antisense RNA. To enhance and propagate the antiviral effect of
      antisense RNA, two novel human immunodeficiency virus type 1 (HIV-1)-based vector
      DNAs, designated as pMAG7 and pMAG19, were constructed which contained HIV-1 cis
      acting packaging elements and produced multigenic HIV-1 antisense RNA that could
      target the entire pol, env, vif, vpu, vpr, rev, and tat and portions of gag and
      nef. The two DNAs were identical except that pMAG19 had additional gag coding
      sequences. Cotransfection of pMAG DNA and infectious, cloned HIV-1 DNA in 293
      cells inhibited virus production (81%-98% reduction in reverse transcriptase
      activity) of various T cell-tropic and macrophage-tropic clade B isolates, such
      as NL4-3, YU-2, and JR-CSF. In addition, virion-associated pMAG antisense RNA was
      detected in residual virus particles produced by pNL4-3 in the presence of pMAG7
      DNA, and the antisense sequences were stably transferred by infection of 174 x
      CEM cells. The results suggest that pMAG DNA may confer broad protection against
      HIV-1 by reducing initial virus burden due to antisense RNA and subsequent virus
      spread by propagation of antisense sequences along with wild-type virus.

PMID- 10905552
TI  - Acute toxicology and pharmacokinetic assessment of a ribozyme (ANGIOZYME)
      targeting vascular endothelial growth factor receptor mRNA in the cynomolgus
      monkey.
AB  - The potential acute toxicity of a ribozyme (ANGIOZYME) targeting the flt-1
      vascular endothelial growth factor (VEGF) receptor mRNA was evaluated in
      cynomolgus monkeys following i.v. infusion or s.c. injection. ANGIOZYME was
      administered as a 4-hour i.v. infusion at doses of 10, 30, or 100 mg/kg or a s.c.
      bolus at 100 mg/kg. End points included blood pressure, electrocardiogram (ECG),
      clinical chemistry, hematology, complement factors, coagulation parameters, and
      ribozyme plasma concentrations. ANGIOZYME was well tolerated, with no drug
      associated morbidity or mortality. There was no clear evidence of ANGIOZYME
      related adverse effects in this study. Slight increases in spleen weight and
      lymphoid hyperplasia were observed in several animals. However, these changes
      were not dose dependent. Steady-state concentrations of ANGIOZYME were achieved
      during the 4-hour infusion of 10, 30, or 100 mg/kg. Dose-dependent elimination of
      ANGIOZYME was observed, with faster clearance at the two highest doses. ANGIOZYME
      was slowly absorbed after s.c. administration, resulting in steady-state
      concentrations for the 9-hour sampling period. Monkeys in this toxicology study
      received significant plasma ANGIOZYME exposure by both the s.c. and i.v. routes.

PMID- 10905553
TI  - Antiproliferative effects of steric blocking phosphorodiamidate morpholino
      antisense agents directed against c-myc.
AB  - The phosphorodiamidate Morpholino oligomers (PMO) are a new class of antisense
      agents that inhibit gene expression by binding to RNA and sterically blocking
      processing or translation. In a search for a Morpholino agent that would inhibit
      cell proliferation, it was found that oligomers directed against c-myc, a gene
      involved in control of the cell cycle, were effective. The sequence specificity
      and mechanism of action of one agent were determined. The 20-mer 126 lowers c-myc
      protein levels in treated cells and arrests cells in G0/G1 of the cell cycle. It
      also acts at the RNA level to inhibit normal pre-mRNA splicing and instead
      produces an aberrantly spliced mRNA. Irrelevant and mispair control oligomers
      indicated that the observed antiproliferative effect was sequence specific. This
      was confirmed in a reporter gene model system using a c-myc 5'-untranslated
      region (5'-UTR) fused to a cDNA copy of the insect luciferase gene. We conclude
      that 126 is acting through an antisense mechanism involving Watson-Crick hydrogen
      bonding to its target RNA. A specific antisense agent directed against a cell
      cycle-associated gene mRNA may be useful as a therapeutic in diseases
      characterized by excess cell proliferation, such as restenosis following balloon
      angioplasty or cancer.

PMID- 10905554
TI  - A cationic derivative of amphotericin B as a novel delivery system for antisense
      oligonucleotides.
AB  - A novel approach based on a plasma membrane permeability-disturbing agent was
      proposed as an antisense oligonucleotide delivery system. AMA, a derivative of
      the polyene antibiotic amphotericin B, formed a stable complex when mixed with
      phosphodiester oligodeoxynucleotides and enhanced the intracellular uptake of a
      5' fluoresceinated anti-mdr1 20-mer into NIH-MDR-G185 cells. The nonlabeled
      phosphorothioate form of the oligodeoxynucleotide, complexed to AMA, inhibited P
      glycoprotein expression with better efficiency and less nonspecific effects than
      when vectorized by Lipofectin. AMA may thus be a good agent for antisense
      strategy.

PMID- 10905555
TI  - Antisense oligomers for selective suppression of MCP-1 synthesis in human
      pulmonary endothelial cells.
AB  - Endothelial synthesis of the C-C chemokine monocyte chemotactic protein-1 (MCP-1)
      has been implicated in the regulation of monocyte recruitment for extravascular
      pools under both physiologic and inflammatory conditions. We designed and
      characterized five antisense phosphorothioate oligodeoxynucleotides (PS-ODN)
      targeting MCP-1 secretion by human pulmonary artery endothelial cells (HPAEC) and
      pulmonary microvascular endothelial cells (HMVEC-L). The most effective PS-ODN
      (MCP-1 AS 2) dose-dependently suppressed the secretion of MCP-1 but not the
      secretion of the C-X-C chemokine interleukin-8 (IL-8) in both HPAEC and HMVEC-L
      in the nanomolar concentration range. Mismatch controls bearing 2 or 4 bp
      substitutions showed markedly reduced inhibitory capacity. MCP-1 mRNA levels were
      not affected even at the highest PS-ODN doses employed (ribonuclease protection
      assay), suggesting a translational arrest of MCP-1 production. Accordingly, PS
      ODN exhibited no nonspecific side effects on immediate-early gene regulation of
      the transcription factor nuclear factor-kappaB (NF-kappaB), as analyzed by gel
      shift assays. Antisense pretreatment of HPAEC reduced the monocyte chemotactic
      bioactivity liberated from tumor necrosis factor-alpha (TNF-alpha)-activated
      endothelial cells (EC) and reduced the TNF-alpha-induced transendothelial
      monocyte migration. We conclude that nanomolar concentrations of specific
      antisense oligodeoxynucleotides effectively inhibit human endothelial MCP-1
      synthesis and may thus provide a rational approach to modulate monocyte
      recruitment under inflammatory conditions.

PMID- 10905556
TI  - Antisense inhibition of IGF receptor expression in HaCaT keratinocytes: a model
      for antisense strategies in keratinocytes.
AB  - Antisense strategies targeting skin conditions are attractive in concept, with a
      number of possible pathologic conditions, such a psoriasis, apparently suitable
      for such an approach. Because in vitro screening of candidate sequences is
      usually desirable, we have attempted to use a range of new generation cationic
      lipids to produce significant antisense oligodeoxynucleotide (ODN) uptake in an
      immortalized keratinocyte cell line (HaCaT). A large number of commercially
      available lipids were screened for the ability to induce nuclear ODN
      localization: Tfx-50, Tfx-20, Tfx-10, Superfect, Cytofectin GSV, Perfect lipids 1
      8, Lipofectin, and Lipofectamine. All lipids were used at a range of
      concentrations (1-20 microg/ml) and with a range of ODN concentrations (1-1000)
      nM). Of all lipids used, only Cytofectin GSV and Superfect produced significant
      (>30% of cells) levels of nuclear positive cells, with Superfect also producing
      significant toxicity at the effective concentration used. Only two treatments
      produced a significant reduction in target mRNA: insulin-like growth factor-1
      receptor (IGF-1R)-ODN 64 complexed with Cytofectin GSV (27.1% +/- 3.5% of IGF-1R
      mRNA in untreated cells,p < 0.01) and ODN 64 complexed with 10 microg/ml
      Lipofectin (62.2% +/- 3.4% of IGF-1R mRNA in untreated cells, p < 0.05). Only one
      treatment, ODN 64 complexed with Cytofectin GSV, produced a reduction in cell
      growth and survival as assessed by amido black assay. These results demonstrate
      that in HaCaT keratinocytes, Cytofectin GSV alone of all commercially available
      cationic lipids was effective in delivering antisense ODN into cell nuclei such
      that a profound antisense effect could be demonstrated.

PMID- 10905557
TI  - Effect of DNA complexation and freeze-drying on the physicochemical
      characteristics of cationic liposomes.
AB  - We describe the use of saccharides, such as sorbitol, mannitol, sucrose,
      maltodextrin, and dextran, as cyoprotectants for freeze-drying cationic
      liposomes. Saccharides can protect liposomes either by interacting with
      phospholipid headgroups or by forming an amorphous glass surrounding the
      vesicles, thus preventing aggregation, mechanical rupture of membrane, fusion of
      liposomes, and drug leakage. We have particularly considered liposome
      characteristics, such as size, zeta potential, and ability in complexing DNA,
      before and after freeze-drying. Our study indicates that cationic liposomes are
      able to maintain liposome characteristics after lyophilization and rehydration
      and maintain the ability to complex DNA even if the strength of the interaction
      forces was of lower intensity with respect to liposomes before lyophilization.

PMID- 10905558
TI  - Intravenous administration of stabilized antisense lipid particles (SALP) leads
      to activation and expansion of liver natural killer cells.
AB  - Stabilized antisense lipid particles (SALP) have been developed for the systemic
      delivery of oligonucleotides. The impact of intravenous SALP administration was
      measured with respect to activation of natural killer (NK) and NK1.1+ T (NKT)
      cells in the livers of immunocompetent mice. Treatment with a SALP containing a
      highly mitogenic oligonucleotide (INX-6295) generated an increase in NK cytolytic
      activity and cell number within the liver but did not appear to affect the number
      of hepatic NKT cells or their cytolytic activity. The same results were observed
      after intravenous administration of the mitogenic oligonucleotide alone.
      Interestingly, treatment with a SALP containing a weakly mitogenic
      oligonucleotide (INX-6300) also activated the liver NK cells, whereas the
      oligonucleotide alone was unable to elicit these effects. The NK stimulatory
      activity of a SALP containing INX-6300 required both lipid and oligonucleotide
      components. These results demonstrate that in addition to modifying the
      pharmacokinetics and biodistribution of intravenously administered
      oligonucleotides, SALP possess immunostimulatory activity independent of
      oligonucleotide mitogenicity, which can serve as an adjuvant to antisense
      therapies for cancer.

PMID- 10905559
TI  - Comments on evaluation of antisense drugs in the clinic.

PMID- 10905560
TI  - Characterization of a novel immunocytolytic factor secreted by pancreatic
      adenocarcinoma.
AB  - We observed a putative immunocytolytic factor secreted in the supernatant of
      several pancreatic adenocarcinoma cell lines that induces apoptosis in
      lymphocytes. A marked reduction in the viability of the target splenocytes was
      evident after coincubation with the supernatants from various pancreatic
      adenocarcinoma cell lines (human, hamster, and murine). The immunocytolytic
      effect was not evident with the conditioned media of normal pancreatic duct
      epithelial cells or other nonpancreatic tumor cells. Biologic activity of the
      supernatants was determined to be heat sensitive and reside in a 30- to 50-kDa
      range. Immune and functional assays have excluded known immunosuppressive
      factors.

PMID- 10905561
TI  - Inhibition of metastatic carcinoma cell growth in livers by
      poly(I):poly(C)/cationic liposome complex (LIC).
AB  - The complex of poly(I):poly(C) and a new cationic liposome (LIC) has a potent
      antitumor activity against many tumor cell lines in vitro, whereas
      poly(I):poly(C) itself has no such activity. In the present study we tested the
      sensitivity of 21 human colon and pancreatic cancer cell lines to LIC or
      Adriamycin in vitro. The growth of most of the cell lines was strongly inhibited
      by both LIC and Adriamycin in vitro, although a few insensitive cell lines were
      different. We also studied the in vivo antitumor activity of LIC or Adriamycin in
      three experimental liver metastasis models in nude mice using a human pancreatic
      cancer cell line (AsPC-1) and two human colon cancer cell lines (Ls174T and HCC
      M1544). The administration of LIC or Adriamycin was started 3 days after the
      injection of tumor cells. Animals received 0.1 mg/kg LIC IV twice weekly or 5
      mg/kg Adriamycin IV every 5 days during the experiments. LIC showed potent
      antitumor activity in all three liver cancer models. Although Adriamycin had
      potent antitumor activity in the HCC-M1544 model, it had only a moderate effect
      in the AsPC-1 model and at most a weak effect in the Ls174T model. At the
      effective doses LIC did not cause detectable pathological changes in the liver
      and did not elicit toxicity to mice in these models, whereas Adriamycin did
      exhibit toxic effects. These results suggest that LIC is a promising candidate
      drug to treat hepatic metastasis.

PMID- 10905562
TI  - Growth inhibition and antimetastatic effect of antisense poly-DNP-RNA on human
      breast cancer cells.
AB  - The RNase-resistant and membrane-permeable antisense poly-2'-O-(2,4
      dinitrophenyl)-oligoribonucleotides (poly-DNP-RNA) against RIalpha subunit of
      protein kinase A (RIalpha/PKA) has been used to inhibit the growth of human
      breast cancer MDA-MB-231 cells in vitro and in vivo. This antisense poly-DNP-RNA,
      with oligonucleotide sequence GGGCGUGCCUCCUCACUGGC, was found to be an effective
      concentration-dependent inhibitor of MDA-MB-231 cell line, whereas the control
      poly-DNP-RNAs with either random or sense sequence were found completely
      inactive. In situ hybridization studies showed that this antisense inhibitor can
      permeate spontaneously into MDA-MB-231 cells and distribute itself throughout the
      cytoplasm. Intraperitoneal administration of this antisense RIalpha poly-DNP-RNA
      to SCID mice with transplanted MDA-MB-231 cells was found to inhibit the growth
      of the xenografts in a concentration-dependent way, prevent metastasis, and
      drastically reduce mortality.

PMID- 10905563
TI  - Significant increase of adenovirus infectivity in glioma cell lines by
      extracellular domain of hCAR.
AB  - Recombinant adenoviruses are highly advantageous as vectors for transferring
      genes into mammalian cells, but the transfer is not efficient in all types of
      cells. We investigated the effects of four adenoviral receptors [integrinalphav,
      integrinbeta3, integrinbeta5, and human coxsackievirus and adenovirus receptor
      (hCAR)] on adenovirus-mediated transfer of exogenous cDNA into each of 10 glioma
      cell lines. Transfection efficiency varied widely from one cell line to another
      (0-100%) when we measured it by infection with AdLacZ, a vector designed to
      express beta-galactosidase. Levels of integrinalphav and integrinbeta5 expression
      were similar among the 10 cell lines, but expression of hCAR and integrinbeta3
      varied significantly. As these observations indicated a possible correlation
      between expression of hCAR and the efficiency of gene transfer, we induced the
      hCAR gene into three glioma cell lines (T98G, U118MG, and U138MG) that expressed
      hCAR at very low levels and had also revealed low efficiencies of adenoviral gene
      transfer. In U118MG- and U138MG-derived cells that had regained the ability to
      express hCAR in stable fashion, adenovirus-mediated gene transfer became highly
      efficient. Moreover, addition of the peptide corresponding to the extracellular
      domain of hCAR (ECD-hCAR) by preincubation significantly increased the adenovirus
      infectivity to these adenovirus-tolerant cells. These results suggest that hCAR
      could be one of important determinants of the infectivity of adenovirus, and that
      the ECD-hCAR might be a novel useful tool for improvement of adenovirus-mediated
      gene therapy against the adenovirus-tolerant cancer cells.

PMID- 10905564
TI  - P450-expression in brain tumors.
AB  - Oxazaphosphorines are inactive anticancer prodrugs that are bioactivated by
      hepatic cytochrome P450. Besides hepatic metabolism, there is increasing interest
      in the possibility of intratumoral activation of oxazaphosphorines by P450.
      Therefore, we investigated the expression of P450 (CYP3A4, CYP3A5, CYP2C9) by RT
      PCR in 10 different brain tumor samples. Because P450 may be downregulated by
      interleukin-1 (IL-1) and IL-6, the receptors for IL-1 and IL-6 were analyzed.
      None of the brain tumors was positive for CYP3A4 whereas CYP3A5 was detected in 3
      out of 10 tumors (two meningeomas, one medulloblastoma grade IV). All five
      gliomas, an ependymoma, and a lymphoma-metastase gave no signal. CYP2C9 mRNA was
      present in every sample studied. All samples were positive for IL-1 and IL-6
      receptors. In summary, we have demonstrated that tumors of the CNS express P450,
      indicating that activation of prodrugs like oxazaphosphorines may take place
      intratumorally. However, the most abundantly hepatically expressed CYP3A4 enzyme
      is absent in the brain tumor samples. The presence of the IL-1 and IL-6 receptors
      opens the possibility that the wellknown downregulating influence of these
      cytokines also takes place in brain tumors.

PMID- 10905565
TI  - A clinical-pharmacological evaluation of percutaneous isolated hepatic infusion
      of doxorubicin in patients with unresectable liver tumors.
AB  - A dose escalation study of hepatic arterial infusion of doxorubicin during
      hemodynamic isolation of the liver (the Delcath system) was conducted to: 1)
      study the pharmacokinetics of regional doxorubicin therapy, and 2) define
      therapeutic efficacy in the treatment of unresectable liver tumors. Eighteen
      patients with unresectable primary or metastatic tumor in the liver were treated
      with 57 procedures. Pharmacokinetic studies were performed on all treatments.
      Hepatic extraction ratio of doxorubicin remained constant at 60.3+/-12.1%.
      independent of the dose escalation. The calculated intrahepatic concentration of
      doxorubicin ranged from 30 to 88 microg/ml when the dosage of doxorubicin was
      escalated from 50 to 120 mg/m2. Dose-limiting systemic toxicity (grade 4
      myelosuppression) was observed at 120 mg/m2. Twelve of 14 patients who received
      more than one treatment at 90 or 120 mg/m2 were evaluable for disease response:
      there were 4 partial responses, 3 minor responses, I stable disease, and 4
      progressive disease. The median overall survival of responders was 23 months, and
      for nonresponders it was 8 months. We have demonstrated a dose-response effect of
      hepatic infusion of doxorubicin at 90 and 120 mg/m2 in advanced hepatic
      malignancies. The isolated hepatic perfusion system improves the therapeutic
      index of doxorubicin and provides pharmacologic justification for its use in the
      treatment of unresectable hepatic malignancies, especially metastatic melanoma
      and sarcoma.

PMID- 10905566
TI  - Elevated antibody levels to Epstein-Bbarr virus antigens in patients with hairy
      cell leukemia compared to controls in relation to exposure to pesticides, organic
      solvents, animals, and exhausts.
AB  - Epstein-Barr virus (EBV) is a B-lymphotropic human herpes virus infecting B
      cells, which has been associated with lymphoid malignancies, above all non
      Hodgkin lymphomas (NHL). Severe immunosuppression is the best recognized risk
      factor for NHL. Many factors in the environment that have been described as risk
      factors for NHL cause measurable changes in immune functions. Hairy cell leukemia
      (HCL) is a rare, indolent non-Hodgkin lymphoma, originating from B-lymphocytes.
      This was a case-control study including 111 male cases with HCL and 400 controls.
      In a subgroup of 57 cases and 65 controls analysis of antibodies to EBV early
      antigen, viral capsid antigen, and EBNA-1, measured as P107, was performed. In
      this study, we confirm other studies describing elevated levels of antibodies to
      the EBV early antigen (EA) in patients with HCL compared to controls. We found
      only minor differences in the levels of antibodies to the viral capsid antigen
      (VCA) and EBNA-1. measured as P107. We found a positive association of a titer to
      EA IgG > or =40 (OR 4.1; CI 1.9-9.5). The ORs were further elevated when subjects
      with high levels of EA IgG and exposed to environmental agents such as organic
      solvents, certain pesticides, impregnating agents, animals, and exhausts were
      compared to those subjects with low levels that were not exposed. Antibody
      reactivity against the EBV EBNA 1-alanine-glycine repeat (P107 IgG) above the
      median gave an increased OR for HCL, which further increased in subjects exposed
      to organic solvents, certain pesticides. impregnating agents, animals, and
      exhausts. However, the numbers of exposed cases and controls were small in some
      of the calculations.

PMID- 10905567
TI  - Impact of hypoxemia on the performance of cerebral oximeter in volunteer
      subjects.
AB  - Adverse neurological events during hypoxic episodes in high-risk patients or in
      patients not thought to be at risk while undergoing procedures increase morbidity
      and mortality. The ability to reliably monitor cerebral oxygenation could serve
      as an indicator for the need of therapeutic intervention and it's overall effect.
      This study was designed to verify the reliability of the only commercially
      available continuous noninvasive monitor, the INVOS 3100 (Somanetics Corp., Troy,
      MI), in subjects with varying levels of hypoxemia. Six adult volunteer subjects
      were enrolled. After placement of electrocardiogram (EKG), noninvasive blood
      pressure (NIBP), pulse oximeter (SpO2), cerebral oximeter (rSO2), a 20 g radial
      artery catheter, and a 4 F oximetric jugular bulb catheter, the subjects were
      given hypoxic mixtures to breathe to varying levels of desaturation. Arterial and
      mixed venous blood was drawn for blood-gas analysis at each level of O2
      saturation. The cerebral hemoglobin saturation value from the cerebral oximeter
      was compared to the combined brain saturation using the formula: estimated field
      saturation between the light source and the detector (fSO2) = 0.25 x the arterial
      oxygen saturation (SaO2) + 0.75 x the jugular bulb venous oxygen saturation
      (SjvO2), (fSO2 = 0.25 SaO2 + 0.75 SjvO2). Statistical analysis demonstrated a
      correlation of 0.67 between rSO2 and fSO2 and a bias of -3.1% with a precision of
      12.1%. Minimal bias of 0.38% and precision of 6.22% were calculated for
      transitional error. We concluded from the study that rSO2 may serve as a reliable
      indicator of changes in brain oxygenation induced by hypoxemia.

PMID- 10905568
TI  - Cerebrovascular tone rather than intracranial pressure determines the effective
      downstream pressure of the cerebral circulation in the absence of intracranial
      hypertension.
AB  - Cerebral perfusion pressure is commonly calculated from the difference between
      mean arterial pressure and intracranial pressure because intracranial pressure is
      known to represent the effective downstream pressure of the cerebral circulation.
      Studies of other organs, however, have shown that effective downstream pressure
      is determined by a critical closing pressure located at the arteriolar level.
      This study was designed to investigate the effects of PCO2-induced variations in
      cerebrovascular tone on the effective downstream pressure of the cerebral
      circulation. Sixteen patients recovering from head injury were studied.
      Intracranial pressure was assessed by epidural pressure transducers. Blood flow
      velocity in the middle cerebral artery was monitored by transcranial Doppler
      sonography. Effective downstream pressure was derived from the zero flow pressure
      as extrapolated by regression analysis of instantaneous arterial pressure/middle
      cerebral artery flow velocity relationships. PaCO2 was varied between 30 and 47
      mm Hg in randomized sequence. Intracranial pressure decreased from 18.5+/-5.2 mm
      Hg during hypercapnia to 9.9+/-3.1 mm Hg during hypocapnia. In contrast,
      effective downstream pressure increased from 13.7+/-9.6 mm Hg to 23.4+/-8.6 mm Hg
      and exceeded intracranial pressure at hypocapnic PaCO2 levels. Our results
      demonstrate that, in the absence of intracranial hypertension, intracranial
      pressure does not necessarily represent the effective downstream pressure of the
      cerebral circulation. Instead, the tone of cerebral resistance vessels seems to
      determine effective downstream pressure. This suggests a modified model of the
      cerebral circulation based on the existence of two Starling resistors in a series
      connection.

PMID- 10905569
TI  - Perioperative intracranial hemorrhage in achondroplasia: a case report.
AB  - We report a case of a 35-year-old man with achondroplasia who previously had
      thoracolumbar decompressive laminectomies, who developed recurrence of spinal
      stenosis at the thoracolumbar junction. The patient underwent standard repeat
      thoracolumbar decompression, removal of a disc, and spinal fusion with
      instrumentation in the prone position. Postoperatively the patient was confused.
      Computed tomography (CT) revealed hemorrhages in both cerebellar hemispheres with
      surrounding edema and mild mass effect. These were interpreted as venous
      hemorrhages. Conservative therapy was successful. This is the first case report
      of perioperative venous intracranial hemorrhage in the context of spinal surgery
      for achondroplasia. Distinctive anatomic characteristics of achondroplasia,
      combined with several potentially modifiable aspects of his management, may have
      predisposed the patient to this complication.

PMID- 10905570
TI  - Fatal fat embolism syndrome: a case report.
AB  - Fat embolism syndrome is a dire complication of long bone trauma. It is usually
      associated with neurological, hematological and respiratory involvement, the
      latter being the major cause of death. We present a case of severe fat embolism
      syndrome occurring 3 hours after a long bone injury, leading to permanent
      vegetative state and death without any respiratory signs. The diagnosis was
      confirmed by cytology of the bronchoalveolar lavage fluid. Clinical presentation
      of the puzzling fat embolism syndrome and diagnostic tests in suspected fat
      embolism syndrome are reviewed.

PMID- 10905572
TI  - Recurrent intracerebral hemorrhages in cerebral amyloid angiopathy: a case
      report.
AB  - Cerebral amyloid angiopathy frequently causes recurrent intracerebral hemorrhages
      in elderly patients who do not have systemic hypertension. Surgery should be
      reserved for conditions which cannot be controlled by medical treatment. When
      surgery is needed, potential complications (such as bleeding near the operation
      site or remote area) should be kept in mind. A case study of a 66-year-old woman
      with cerebral amyloid angiopathy and recurrent intracerebral hemorrhages is
      presented.

PMID- 10905571
TI  - Exaggerated hemodynamic responses to nasal injection and awakening from
      anesthesia in a Cushingoid patient having transsphenoidal hypophysectomy.
AB  - A 51-year-old female patient, with an adrenocorticotrophic hormone-secreting
      pituitary tumor, was scheduled for transphenoidal hypophysectomy. She had a
      history of recent onset diabetes mellitus and a 2-year history of arterial
      hypertension. Despite ongoing medical therapy, preoperative blood pressure was
      150-160/90-120 mm Hg. During general anesthesia, in response to perinasal
      infiltration with 10 ml of a solution containing lidocaine 200 mg and epinephrine
      100 microg, blood pressure increased from 144/80 mm Hg to 317/175 over 3 minutes,
      as assessed by direct blood pressure monitoring. At the completion of the
      anesthetic, as the patient awakened and coughed and moved, blood pressure again
      increased dramatically, this time from 154/87 mm Hg to 285/170 over 3 minutes.
      Five months postoperatively, the patient's serum cortisol concentrations had
      normalized and her cuff blood pressure was 126/82, despite a reduction in her
      antihypertensive medications. The dramatic intraoperative blood pressure changes
      in this patient were attributed to the effects of hypercortisolemia on the normal
      physiologic responses to epinephrine and patient movement.

PMID- 10905573
TI  - Transcranial Doppler monitoring during carotid endarterectomy: a technical case
      report.
AB  - We report a case involving a patient undergoing carotid endarterectomy in whom
      transcranial doppler monitoring demonstrated impaired cerebral blood flow during
      the initial dissection of the carotid artery, during cross-clamping of the
      carotid artery, and after the shunt was kinked inadvertently. Only when the
      carotid artery was cross-clamped were these ischemic changes also seen by
      electroencephalography. During the other episodes, the electroencephalography
      tracings demonstrated no detectable changes. This case illustrates the importance
      of using multiple modalities to determine the adequacy of cerebral blood flow and
      neuronal integrity.

PMID- 10905574
TI  - Effects of mild versus deep hypothermia on a cloned human brain glutamate
      transporter (GLT-1) expressed in Chinese hamster ovary cells.
AB  - Glutamate transporters, widely distributed in the brain and spinal cord, maintain
      extracellular glutamate concentrations below neurotoxic levels. In cerebral
      ischemia/anoxia, the glutamate transporter runs in reverse and releases glutamate
      into the extracellular space, causing irreversible neuronal damage. Although
      hypothermia reduces the elevation of extracellular glutamate concentration during
      cerebral ischemia/anoxia, little is known about the effect of hypothermia on the
      glutamate transporter. A human glial glutamate transporter (hGLT-1) cDNA was
      isolated by screening a human cerebral cortical library, and cloned cDNA was
      stably transfected in Chinese hamster ovary (CHO) cells. Effects of deep
      hypothermia (22 to 23 degrees C) on uptake and release of L-glutamate via hGLT-1
      were investigated by whole-cell patch-clamp. The control study was performed at
      34 to 35 degrees C. The hGLT-1 transporter had the capacity to take up
      extracellular L-glutamate under essentially physiological ionic conditions,
      whereas this transporter promoted release of L-glutamate under a nonphysiological
      condition mimicking complete ischemia. Deep hypothermia decreased a) uptake and
      b) release of L-glutamate via hGLT-1 to a) 4.8+/-4.8% (P < .01, n = 7) and b)
      19.0+/-4.5% (P < .01, n = 15) of control values, respectively. The results
      suggest that deep hypothermia is a potent inhibitor of glutamate uptake by intact
      glial cells as well as glutamate release from glial cells under certain
      pathophysiological circumstances. The balance between these antagonistic effects
      of hypothermia may attenuate the elevation of the extracellular glutamate
      concentration during ischemia/anoxia.

PMID- 10905576
TI  - Influence of anesthesia protocol in experimental traumatic brain injury.
AB  - Most pharmacologic studies on brain trauma in animals are performed while the
      animals are under general anesthesia, which can interfere with brain metabolism
      and modify the experimental results. This study investigates the effects of three
      anesthetic drugs (halothane 2% and 4%, propofol at 10 mg/kg, and chloral hydrate
      at 400 mg/kg) on the traumatic brain injury-induced neurologic deficit in mice.
      Trauma was induced with a weight-drop device. For each drug, animals were divided
      into four groups; the first did not receive either anesthesia or trauma, the
      second received anesthesia but no trauma, the third received a trauma without
      anesthesia, and the fourth received anesthesia before the trauma. A neurologic
      examination using two different scorings (string and grip test) was performed 1
      hour and 24 hours after the trauma. Mortality after trauma was increased for
      halothane 4% (48% versus 20% in unanesthetized mice), propofol (80% versus 30%),
      and chloral hydrate (70% versus 44%). Halothane 2% did not increase the mortality
      in traumatized mice. Halothane 2% or 4% anesthesia did not modify the string
      score after the trauma. Grip score after the trauma was better in mice
      anesthetized with halothane at either 2% or 4%. Mice injured under anesthesia
      with chloral hydrate had worse grip and string scores (P < .05) than
      unanesthetized mice. These results lead us to question the influence of
      anesthesia on the results obtained in experimental neuropharmacologic studies,
      particularly when there are discrepancies between two studies on the same
      pharmacologic treatment, which differ in their anesthesia protocols.

PMID- 10905575
TI  - Threshold of ischemic depolarization for neuronal injury following four-vessel
      occlusion in the rat cortex.
AB  - Previous studies have indicated that prolonging the onset of ischemic
      depolarization reduces neuronal damage. However, the relationship between the
      duration of ischemic depolarization and its histological outcome has not been
      quantitatively evaluated. Rats were anesthetized (with 1% halothane), intubated,
      and placed in a stereotaxic frame. Direct current (DC)-potential in the 5th layer
      of the parietal cortex was measured. Changes in cerebral blood flow (CBF) were
      monitored by a laser-Doppler flow probe placed adjacent to the DC-electrode.
      Animals were subjected to four-vessel occlusion for 5 minutes, 10 minutes, or 20
      minutes. The histological outcome was evaluated at the DC-recorded site 7 days
      after the insult. Initiation of ischemia reduced CBF to 9%-28% of the preischemic
      value. Initial DC-deflection (14+/-3 mV), indicating ischemic depolarization, was
      observed at 172+/-112 seconds after the onset of ischemia. Total durations of
      ischemic depolarization were 6.4+/-1.5 minutes, 10.6+/-3.5 minutes and 19.8+/-4.6
      minutes in rats in which ischemia was induced for 5 minutes, 10 minutes, and 20
      minutes, respectively. The regression curve showed that there was a close
      relationship between percentage of damaged neurons and duration of ischemic
      depolarization (r2 = 0.80, P = .001). The durations of ischemic depolarization
      for neuronal injury in 30%, 50%, and 70% of pyramidal neurons in the parietal
      cortex were 15.6 minutes (95% confidence interval, 14.2-17.0 minutes), 20.3
      minutes (18.5-22.7 minutes) and 25.0 minutes (22.7-28.5 minutes), respectively.
      It is thought that shortening the duration of ischemic depolarization is a
      rational approach for reducing the severity of ischemic injury.

PMID- 10905577
TI  - Neuroendoscopic procedures: anesthetic considerations for a growing trend: a
      review.
AB  - The recent trend in neurosurgery is shifting toward further reduction in
      invasiveness to minimize trauma to the brain. Endoscopy holds the promise of
      shortened hospital stay with improved postoperative outcome. An important
      minimally invasive technique is neuroendoscopy. The ventricular system and
      subarachnoid space of the brain provide suitable conditions for the use of an
      endoscope. The currently available literature focuses only on recent advances in
      neuroendoscopy from the surgical perspective. To date, there is paucity of
      anesthetic literature emphasizing the implications for this growing trend. The
      surgical technique, instrumentation, anesthetic requirements, potential pitfalls
      and complications of this technique must be completely understood to ensure a
      successful outcome. The purpose of this review is to provide knowledge of
      indications, instrumentation, and anesthetic considerations in anticipation of
      complications steming from this procedure.

PMID- 10905578
TI  - Giraffes, siphons, and starling resistors. Cerebral perfusion pressure revisited.

PMID- 10905579
TI  - Downregulation of ileal bile acid absorption in bile-duct-ligated rats.
AB  - BACKGROUND/AIMS: Accumulation of toxic bile acids in cholestasis contributes to
      liver injury and depends on their synthesis, secretion and intestinal absorption.
      In the present study, we investigated the effect of cholestasis on the active
      ileal absorption of bile acids in vivo and the adaptation of transporters
      involved in ileal bile acid absorption. METHODS: Male Wistar rats underwent
      ligation of the common bile duct or biliary diversion. Sham-operated rats served
      as controls. Active ileal bile acid absorption of taurocholate was measured by an
      intestinal perfusion technique. Transporter mRNA levels of the Na+/bile acid
      cotransporting protein (IBAT), ileal lipid binding protein (ILBP) and organic
      anion transporter subtype 3 (Oatp3) and protein expression of IBAT and ILBP were
      determined in the distal ileum. RESULTS: After bile duct ligation the intestinal
      absorption rates of taurocholate were lower (p<0.05) and after biliary diversion
      absorption rates were higher compared to sham-operated animals (p<0.05). The
      absorption rates were inversely correlated to serum bile acid concentrations.
      Levels of IBAT-, ILBP- and Oatp3- mRNA were not different between the groups.
      However, in cholestatic rats, the expression of the 99-kDa dimer of IBAT was
      decreased compared to controls (p<0.05), whereas the 46-kDa monomeric protein of
      IBAT and the expression of ILBP was unchanged. After biliary diversion a similar
      pattern of protein expression was observed, despite an increased absorption rate.
      CONCLUSIONS: Cholestasis leads to a decreased active ileal absorption of
      taurocholate. The changes in protein expression may not account for the different
      absorption rates. The intestinal absorption of bile acids seems to be regulated
      by their systemic concentration.

PMID- 10905580
TI  - Amplification and sequence analysis of partial bacterial 16S ribosomal RNA gene
      in gallbladder bile from patients with primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: The etiopathogenesis of bile duct lesion in primary biliary
      cirrhosis is unknown, though the participation of bacteria and/or their
      components and products is suspected. In this study, we tried to detect and
      identify bacteria in the bile of patients with primary biliary cirrhosis by
      polymerase chain reaction using universal bacterial primers of the 16S ribosomal
      RNA gene. METHODS: Gallbladder bile samples from 15 patients with primary biliary
      cirrhosis, 5 with primary sclerosing cholangitis, 5 with hepatitis C virus
      related liver cirrhosis, 11 with cholecystolithiasis, and from 12 normal adult
      gallbladders were used. In addition to the culture study, partial bacterial 16S
      ribosomal RNA gene was amplified by polymerase chain reaction (PCR) taking
      advantage of universal primers that can amplify the gene of almost all bacterial
      species, and the amplicons were cloned and sequenced. Sequence homology with
      specific bacterial species was analyzed by database research. Bacterial
      contamination at every step of the bile sampling, DNA extraction and PCR study
      was avoided. Furthermore, to confirm whether bacterial DNA is detectable in liver
      explants, the same analysis was performed using 10 liver explants of patients
      with primary biliary cirrhosis. RESULTS: In primary biliary cirrhosis, 75%
      (p<0.0001) of 100 clones were identified as so-called gram-positive cocci while
      these cocci were positive in only 5% in cholecystolithiasis (p<0.0001). In
      cholecystolithiasis gram-negative rods were predominant instead. One bacterial
      species detected in a normal adult was not related to those detected in primary
      biliary cirrhosis and cholecystolithiasis patients. No bacterial DNA was detected
      by PCR amplification in 10 liver explants of patients with primary biliary
      cirrhosis. CONCLUSIONS: The present results raise several possible roles of gram
      positive bacteria in bile in the etiopathogenesis of primary biliary cirrhosis.
      However, these results could also reflect an epiphenomenon due to decreased bile
      flow in the patients with primary biliary cirrhosis at an advanced stage.

PMID- 10905581
TI  - Differential leptin responses to acute and chronic biliary obstruction in rats.
AB  - BACKGROUND/AIMS: Recently leptin, a protein released from adipocytes, has been
      identified as a potent circulating satiety factor. We therefore undertook this
      series of experiments to examine leptin's role in the anorexia associated with
      biliary obstruction. METHODS: Rats underwent either surgical bile duct resection
      (BDR) or sham resection (sham). Body weight, and food and water intake were
      measured during a baseline period and for 8 days after surgery. At 4, 8 and 16 h
      as well as on days 2, 4, 6, and 8 postsurgery, sham and BDR rats were sacrificed
      and sera collected for subsequent measurement of leptin hormone concentration by
      RIA. White adipose tissue was collected on days 2, 4, 6 and 8 for leptin mRNA
      determination by Northern blot. RESULTS: Obstructive cholestasis in BDR rats
      caused significant anorexia for up to 7 days post-surgery, whereas in sham rats,
      a significant decrease in food intake was only observed in the first 24-h period
      following surgery. In both sham and BDR rats, water intake was significantly
      decreased during the first 24-h period after surgery, but had recovered to
      baseline levels by day 2 in both groups. Fat pad mass corrected to body weight
      was not significantly different between the two experimental groups. Serum leptin
      levels were significantly increased 4 and 8 h after surgery, had normalized by 16
      h post-surgery, and were then decreased in BDR rats on days 2, 4, 6 and 8
      compared with controls. Leptin mRNA levels in epididymal fat pads were decreased
      by approximately 2-fold in BDR rats compared with sham rats on days 2, 4, 6 and
      8. Furthermore, day 5 BDR and sham rats demonstrated similar anorectic responses
      to centrally administered leptin. CONCLUSIONS: Leptin production is significantly
      increased early after biliary obstruction but is reduced after prolonged biliary
      obstruction. Increased circulating leptin levels may contribute to the profound
      anorexia observed early after biliary obstruction but appear not to mediate the
      anorexia observed during more chronic biliary obstruction.

PMID- 10905582
TI  - The role of nitric oxide in the reduction of protein kinase C-induced contractile
      response in aortae from rats with portal hypertension.
AB  - BACKGROUND/AIMS: Protein kinase C plays a role in the regulation of vascular cell
      contraction but its activity may be reduced by nitric oxide. In portal
      hypertension, the exact mechanism by which nitric oxide induces vascular
      hyporeactivity to vasoconstrictors is unclear. The aim of this study was to
      investigate the role of the interaction of nitric oxide and protein kinase C in
      the vascular reactivity in isolated aortae from portal vein-stenosed rats.
      METHODS/RESULTS: The contractile response to phorbol 12,13-dibutyrate, a protein
      kinase C activator, was significantly reduced in portal vein-stenosed aortae
      compared to sham-operated aortae. Preincubation with N-nitro-L-arginine or
      endothelium removal enhanced the response to phorbol 12,13-dibutyrate. The
      hyporesponsiveness to phorbol 12,13-dibutyrate in portal vein-stenosed rat aortae
      was only corrected after endothelium removal. The time course of contractions
      induced by phorbol 12,13-dibutyrate showed that the contraction was maintained
      for 2 h in sham-operated aortae and decreased to baseline in portal vein-stenosed
      rat aortae. This decrease was inhibited by N-nitro-L-arginine preincubation or
      endothelium removal. Protein kinase C downregulation caused a more marked
      reduction of phenylephrine-induced contraction in portal vein-stenosed aortae
      than in sham-operated aortae. The time course of total nitric oxide synthase
      activity in the presence of phorbol 12,13-dibutyrate showed a decrease in nitric
      oxide synthase activity after 30 min in both groups. Nitric oxide synthase
      activity remained stable for 120 min in sham-operated aortae but returned to
      basal level in portal vein-stenosed aortae. CONCLUSIONS: Hyporeactivity to
      vasoconstrictors in portal vein-stenosed rat aortae may be due, in part, to a
      decrease in protein kinase C activation caused by nitric oxide overproduction.

PMID- 10905583
TI  - Serum leptin levels in patients with viral chronic hepatitis or liver cirrhosis.
AB  - BACKGROUND/AIM: Serum levels of leptin, the adipocyte-derived hormone regulating
      food intake and energy expenditure in mammals, have been found to be increased in
      cirrhotic patients. The aim of the present study was to investigate leptin serum
      level in relation to anthropometric features and liver function in patients with
      viral chronic hepatitis or liver cirrhosis. METHODS: Serum leptin levels were
      determined by radioimmunoassay in 30 male and 10 female patients with chronic
      hepatitis, in 42 male and 10 female patients with liver cirrhosis, and in four
      respective control groups. Liver function was evaluated by the
      monoethylglycinexylidide formation test. Body mass index and body fat mass were
      estimated by weight, height and skinfold thickness measurements. RESULTS:
      Compared with controls, absolute serum leptin levels were significantly (p<0.01)
      lower in chronic hepatitis patients and similar in cirrhotic patients. Leptin
      serum levels were significantly (p<0.05) higher in cirrhotic than in chronic
      hepatitis patients. When expressed in relation to body fat mass, the above
      differences persisted; however, cirrhotic females showed significantly (p<0.05)
      higher serum leptin values than controls. Serum leptin values correlated
      negatively (p<0.01) with monoethylglycinexylidide serum values in all groups of
      patients. CONCLUSIONS: In patients with chronic viral liver disease, serum leptin
      levels tend to increase as liver function worsens. This may reflect a decline in
      the ability to downregulate energy expenditure as an adaptation to anorexia
      and/or to defective substrate utilisation due to liver disease and may negatively
      influence body weight homeostasis in these patients.

PMID- 10905584
TI  - Serum leptin levels in post-hepatitis liver cirrhosis.
AB  - BACKGROUND/AIMS: Little information is available on the involvement of leptin in
      clinical conditions associated with malnutrition, such as liver cirrhosis. The
      behaviour of serum leptin in patients with different Child-Pugh score, post
      hepatitis liver cirrhosis and insulin sensitivity has therefore been investigated
      and compared with that in alcoholic Child C patients. METHODS: Sixty-four
      patients, aged 51 to 62 years, with different degrees of post-hepatitis cirrhosis
      or Child C alcoholic cirrhosis were compared with 15 age-matched control
      subjects. Body composition was estimated by skinfold thickness. Serum leptin,
      glucose and insulin were assayed. RESULTS: In post-hepatitis patients a
      significant reduction in leptin levels was observed as the Child-Pugh score
      worsened (men: 2.94+/-1.61 in Child C vs 6.78+/-2.49 ng/ml in controls, p<0.001;
      women: 4.14+/-0.66 in Child C vs 16.16+/-3.90 ng/ml in controls, p<0.02).
      Conversely, only the men with alcoholic liver cirrhosis showed a significant
      difference in leptin concentration compared to controls (8.5+/-2.1 vs 16.4+/-7.9
      kg, p<0.05). In particular, Child C, alcoholic cirrhotic women had a
      significantly (p=0.03) higher level of leptin than post-hepatitis matched women.
      A positive correlation was observed between leptin and fat mass (men R2=0.59,
      p<0.0001 and women R2=0.65, p<0.0001). While fasting levels of serum leptin
      correlated significantly with insulin concentrations in controls, a similar
      relationship was not observed in the cirrhotic population, which displayed higher
      insulin concentrations than controls. CONCLUSIONS: In contrast to findings in
      alcoholic cirrhotic women, low leptin values in post-hepatitis cirrhotic patients
      mainly represent the expression of a reduced fat mass.

PMID- 10905585
TI  - Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal
      syndrome.
AB  - BACKGROUND/AIM: Ornipressin, a vasopressin analog with potent splanchnic
      vasoconstrictor action, has been shown to reverse hepatorenal syndrome. However,
      its usefulness in clinical practice is limited by frequent ischemic
      complications. The aim of this study was to assess the efficacy of terlipressin,
      an analog of vasopressin with a low profile of side effects, plus albumin in this
      condition. METHODS: Nine consecutive patients with cirrhosis and hepatorenal
      syndrome were included in a pilot study of terlipressin (0.5-2 mg/4 h i.v.)
      therapy associated with iv albumin. RESULTS: Treatment (9 days, range 5-15) was
      associated with a marked reduction of serum creatinine (3.9+/-0.7 to 1.3+/-0.1
      mg/dl, p<0.001, mean+/-SE). Reversal of hepatorenal syndrome (reduction of
      creatinine below 1.5 mg/dl) was observed in seven of the nine patients. There was
      a remarkable improvement in circulatory function, with an increase in mean
      arterial pressure (68+/-2 to 80+/-4 mmHg, p<0.05) and suppression of
      vasoconstrictor systems activity (plasma renin activity and plasma norepinephrine
      decreased from 23+/-12 ng/ml x h and 1549+/-373 pg/ml to 3.5+/-2 ng/ml x h and
      373+/-98 pg/ml, respectively, p<0.01 for both). No patient developed signs of
      intestinal, myocardial or distal ischemia. CONCLUSIONS: Terlipressin associated
      with albumin appears to be a safe and effective treatment of hepatorenal
      syndrome.

PMID- 10905586
TI  - Nuclear factor kappaB in proliferation, activation, and apoptosis in rat hepatic
      stellate cells.
AB  - BACKGROUND/AIMS: Activation of the transcription factor NFkappaB has been
      demonstrated in activated hepatic stellate cells (HSCs). We investigated the role
      of NFkappaB in proliferation, in activation, and in TNFalpha-induced apoptosis of
      HSCs. METHODS: NFkappaB activation was inhibited using an adenovirus expressing
      an IkappaB dominant negative protein (Ad5IkappaB) in both quiescent and activated
      HSCs. Quiescent HSCs were infected with Ad5IkappaB or an adenovirus expressing
      beta-galactosidase (Ad5LacZ). The cells were cultured for 7 days. HSCs activation
      was determined by cell morphology, smooth muscle alpha-actin (alpha-sma)
      expression, and steady-state mRNA levels of alpha1(I) collagen as assessed by
      Western blot and RNase protection assay, respectively. Proliferation was
      determined in culture-activated HSCs by 3H-thymidine incorporation and direct
      cell counting. Apoptosis was analyzed by infecting quiescent or activated HSCs
      with Ad5IkappaB or Ad5LacZ, and then treating with TNFalpha. Apoptosis was
      demonstrated by determining cell number, assessing nuclear morphology, TUNEL
      assay and caspase 3 activity. RESULTS: After 7 days in culture no differences
      were noted between the Ad5IkappaB- and the Ad5LacZ-infected cells in the
      morphology, alpha-sma expression or in alpha1(I) collagen mRNA levels. Ad5IkappaB
      infection did not modify proliferation in activated HSCs. TNFalpha induced
      apoptosis only in Ad5IkappaB-infected activated, but not quiescent HSCs.
      Apoptosis was initially demonstrated 12 h after exposure to TNFalpha. Twenty-four
      h after the TNFalpha treatment, 60% of the activated HSCs were apoptotic.
      CONCLUSION: NFkappaB activity is not required for proliferation or activation of
      HSCs; however, NFkappaB protects activated HSCs against TNFalpha-induced
      apoptosis.

PMID- 10905587
TI  - Obstructive jaundice impairs hepatic sinusoidal endothelial cell function and
      renders liver susceptible to hepatic ischemia/reperfusion.
AB  - BACKGROUND/AIMS: Obstructive jaundice is associated with increased surgical
      morbidity and mortality. While parenchymal injury has been defined in obstructive
      jaundice, the pathogenesis of hepatic sinusoidal endothelial cell injury in
      obstructive jaundice is unclear. The aims of this study were to investigate
      hepatic sinusoidal endothelial cell injury in obstructive jaundice by determining
      serum hyaluronic acid levels, purine nucleoside phosphorylase/alanine
      aminotransferase ratios, and hyaluronic acid elimination rate, and also to
      determine whether hepatic parenchymal cell injury in obstructive jaundice is
      induced more than in normal liver after hepatic ischemia/reperfusion. METHODS:
      Male Wistar rats underwent ligation and division of the common bile duct
      (obstructive jaundice group) or sham operation (Sham group). Serum hyaluronic
      acid levels and purine nucleoside phosphorylase/alanine aminotransferase ratios
      in both groups were examined at intervals up to 21 days after surgery. Hepatic
      blood flow, permeability, neutrophil accumulation, and hyaluronic acid
      elimination rates in both groups were measured 14 days after surgery. Changes in
      serum hyaluronic acid and alanine aminotransferase concentrations were determined
      after 15 min of hepatic ischemia followed by reperfusion. RESULTS: Serum
      hyaluronic acid levels remained elevated after bile duct ligation. Hepatic
      sinusoidal endothelial cell swelling was observed by electron microscopy, and
      hepatic permeability was increased 14 days after bile duct ligation in
      association with neutrophil accumulation. Hepatic blood flow in obstructive
      jaundice remained unchanged, but hyaluronic acid elimination capacity was less
      than that in the Sham group. After hepatic reperfusion, the disappearance rate of
      serum hyaluronic acid in obstructive jaundice was lower, and serum alanine
      aminotransferase levels were higher than those in the Sham group. CONCLUSIONS:
      Our findings suggest that obstructive jaundice impairs sinusoidal endothelial
      cells and that sinusoidal endothelial cell damage in association with sinusoidal
      deterioration during obstructive jaundice renders liver susceptible to
      ischemia/reperfusion relative to normal liver.

PMID- 10905589
TI  - The immunohistochemical phenotype of dysplastic foci in human liver: correlation
      with putative progenitor cells.
AB  - BACKGROUND/AIMS: In previous studies we found strong evidence for the existence
      and activation in human liver of putative progenitor cells resembling oval cells
      in rat liver. In view of the known role of rat oval cells in regeneration and
      hepatocarcinogenesis, we investigated a possible correlation between human
      putative progenitor cells and different types of dysplastic foci. METHODS: We
      determined the immunohistochemical phenotype of dysplastic foci found in 20
      cirrhotic liver explants of various etiology, using specific antibodies against
      hepatocyte-type cytokeratin (CK) 8 and CK18, bile duct-type CK7 and CK19,
      chromogranin-A (chrom-A) and rat oval cell marker OV-6. RESULTS: All 12 foci of
      large cell dysplasia had a phenotype similar to that of surrounding parenchyma.
      Oncocytic foci showed a strong cytoplasmic staining for CK7. Three out of six of
      these foci contained "progenitor cells", which are small cells immunoreactive for
      CK18, CK7, CK19, OV-6, chrom-A and stained more intensely for CK8 than
      surrounding hepatocytes. Four out of eight glycogen-storing foci contained CK7
      positive intermediate hepatocyte-like cells and "progenitor cells". Sixteen out
      of 29 small cell dysplastic foci consisted of "progenitor cells" and intermediate
      hepatocyte-like cells which were immunoreactive for CK7, CK18, OV-6, chrom-A and
      showed a stronger cytoplasmic positivity for CK8 than surrounding hepatocytes.
      CONCLUSIONS: Foci of large cell dysplasia show no correlation with putative
      progenitor cells. Half of the oncocytic and glycogen-storing foci contain
      "progenitor cells", while more than half of the foci of small cell dysplasia
      consist of small cells with the same immunohistochemical phenotype as putative
      progenitor cells and intermediate hepatocyte-like cells, suggesting that
      differentiating putative progenitor cells can give rise to foci of small cell
      dysplasia.

PMID- 10905588
TI  - Cold preservation injury in rat liver: effect of liposomally-entrapped adenosine
      triphosphate.
AB  - BACKGROUND/AIMS: Energy charge and capacity for adenosine triphosphate (ATP)
      synthesis have been demonstrated to play a major role in the maintenance of organ
      function after liver preservation for transplantation. The aim of this study was
      to evaluate whether a supply of liposomally-entrapped ATP during preservation
      could improve the energy state and metabolism of cold-stored rat liver. METHODS:
      In the first set of experiments, the uptake of ATP-containing liposomes and their
      effects on hepatic viability were determined in isolated perfused unstored rat
      liver. In the second set of experiments, rat livers were preserved for 18 h at 4
      degrees C in UW solution in the presence of these liposomes, and effects on
      energy state, cell volume and metabolism were evaluated. In each part, data were
      compared with adequate control, unloaded liposome-treated, and free ATP-treated
      groups (n=6 in each group). RESULTS: In non-stored livers, ATP-containing
      liposomes were taken up by the liver; they did not alter hepatic viability and
      induced a decrease in energy substrate consumption (glucose and amino acids), and
      an improvement in intrahepatic ATP content (+23% vs. Control). Addition of
      liposomally-entrapped ATP during cold storage produced a significant attenuation
      of the decrease in hepatic ATP content (Lip ATP 2: 524+/-45 vs. Control 2: 364+/
      106 nmol/g; p<0.05), and induced, during reperfusion, a decrease in proteolysis
      associated with an increase in cell volume compared with the other groups (Lip
      ATP 2: 633+/-63 vs. Control 2: 532+/-38, Unloaded Lip 2: 483+/-55 and Free ATP 2:
      500+/-29 microl/g; p<0.01). CONCLUSIONS: These data indicate that liposomally
      entrapped ATP represents an effective means to improve liver graft energy state
      and function. The decrease in protein degradation may be related to the
      modification of cell volume.

PMID- 10905590
TI  - New target region of allelic loss in hepatocellular carcinomas within a 1-cM
      interval on chromosome 6q23.
AB  - BACKGROUND/AIMS: Frequent allelic losses on the long arm of chromosome 16 in
      several types of human cancers have suggested that 16q harbors one or more genes
      that are important for suppressing tumorigenesis in the tissues in question.
      METHODS: To identify the locations of putative tumor suppressor genes involved in
      hepatocellular carcinoma, we examined 96 primary hepatocellular carcinomas for
      their patterns of allelic loss at 18 microsatellite marker loci distributed along
      this chromosome arm. RESULTS: Allelic loss at one or more loci was observed in 48
      (50%) of these tumors. The highest frequency of loss of heterozygosity (42%) was
      observed with marker D6S311 on chromosome 6q23. Through detailed deletion mapping
      of tumors having partial or interstitial deletions, we identified two commonly
      deleted regions at 6q23 and at 6q26-27. CONCLUSIONS: The common region at 6q23
      lay within a 1-cM interval, flanked by D6S977 and D6S311. The previously
      documented deletion region that includes the M6P/IGF2R locus was confined to a 20
      cM region at band 6q26-27 in our panel of tumors. The location we defined at 6q23
      for a putative suppressor of hepatocellular carcinoma has not been reported
      before.

PMID- 10905591
TI  - Antigen-specific immunotherapy for human papillomavirus 16 E7-expressing tumors
      grown in the liver.
AB  - BACKGROUND/AIMS: We have previously reported a recombinant vaccinia-based vaccine
      (vac-Sig/E7/LAMP-1) that demonstrated a significant anti-tumor effect in a
      subcutaneous tumor challenge model. Since the liver is one of the most common
      sites for tumor metastasis and organ microenvironments may modulate tumor cell
      responses to therapies, the aim of the present study was to evaluate the potency
      of vac-Sig/E7/LAMP-1 in treating E7-expressing tumors grown in the liver.
      METHODS: For in vivo tumor prevention experiments, mice were vaccinated
      intraperitoneally with vac-Sig/E7/LAMP-1 followed by intrahepatic tumor
      challenge. For in vivo tumor regression experiments, mice were first challenged
      with tumor cells and then vaccinated with vac-Sig/E7/LAMP-1 intraperitoneally. In
      addition, enzyme-linked immunospot assays were used to determine the frequency of
      E7-specific T cell precursors. RESULTS: For in vivo tumor protection experiments,
      tumor growth was observed in all of the mice vaccinated with wild-type vaccinia
      and 60% of the mice vaccinated with wild-type E7 vaccinia. All of the mice
      vaccinated with vac-Sig/E7/LAMP-1 remained tumor-free 30 days after tumor
      challenge. For the tumor regression assays, all of the mice vaccinated with vac
      Sig/E7/LAMP-1 remained tumor-free 30 days after vaccination. In contrast, all of
      those mice receiving culture medium, wild-type vaccinia, or wild-type E7 vaccinia
      developed tumors in the liver. In addition, mice vaccinated with vac-Sig/E7/LAMP
      1 had the highest E7-specific CD8+ T cell precursors. CONCLUSIONS: Our data
      suggest that vac-Sig/E7/LAMP-1 is an effective vaccine for controlling E7
      expressing tumors grown in the liver and our model suggests that antigen-specific
      immunotherapy may represent a powerful tool for treating liver tumors with
      characterized tumor-specific antigens. In addition, our data indicate that the
      number of E7-specific CD8+ T cell precursors directly correlated with the anti
      tumor effect generated by Sig/E7/LAMP-1 vaccinia.

PMID- 10905592
TI  - Intratumoral genomic heterogeneity in human hepatocellular carcinoma detected by
      restriction landmark genomic scanning.
AB  - BACKGROUND/AIMS: One of the unique features of advanced hepatocellular carcinoma
      (HCC) is the morphological heterogeneity in a single tumor nodule. In order to
      investigate the intratumoral genomic heterogeneity of HCC, we performed
      Restriction Landmark Genomic Scanning (RLGS), which allows genomic DNAs to be
      surveyed at approximately 2000 landmark sites in a single 2-dimensional gel
      electrophoresis. METHODS: RLGS profiles of two regions from a single HCC nodule
      in six patients were compared with non-tumorous liver tissue. Four HCCs
      consisting of moderately-differentiated cells were separated into several small
      parts by thin fibrous septa, but not encapsulated. DNA samples were obtained from
      both parts of these so-called "nodule-in-nodule" HCC. Two HCCs consisting of well
      differentiated cells which did not have a definite partition appeared
      pathologically homogeneous, and two independent regions of the HCC were used for
      the analysis. RESULTS: All six HCCs demonstrated different RLGS profiles (in
      total about 160 different spots) from the corresponding non-tumorous liver, and
      the number of different spots was greater in the 4 moderately-differentiated
      nodule-in-nodule HCCs (39-68 spots) than in the 2 well-differentiated homogeneous
      HCCs (6 and 3 spots). RLGS profiles of the two parts were different to each other
      in all 4 nodule-in-nodule HCCs. On the other hand, two other homogeneous HCCs
      showed the same RLGS profiles in the two regions. CONCLUSION: Thus, intratumoral
      genomic heterogeneity was demonstrated in the advanced HCC samples, and the
      genomic alterations may relate to the progression of HCC.

PMID- 10905593
TI  - Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3.
AB  - BACKGROUND/AIMS: Patients infected with the hepatitis C virus (HCV) often have
      liver steatosis, suggesting the possibility of a viral cytopathic effect. The aim
      of this study was to correlate the occurrence and severity of liver steatosis
      with HCV RNA type, level and sequence of the core-encoding region. METHODS: We
      scored the liver steatosis in 101 HCV-infected individuals carefully selected to
      exclude other risk factors of a fatty liver. Results were compared with HCV RNA
      genotype and level in serum and liver. In selected patients, we assessed the
      effect of antiviral therapy on steatosis and the relationship between
      nucleocapsid sequence heterogeneity and fat infiltration. RESULTS: Steatosis was
      found in 41 (40.6%) patients, irrespective of sex, age or route of infection. HCV
      genotype 3 was associated with higher steatosis scores than other genotypes. A
      significant correlation between steatosis score and titer of intrahepatic HCV RNA
      was found in patients infected with genotype 3, but not in those infected with
      genotype 1. In selected patients, response to alpha-interferon was associated
      with the disappearance of steatosis. Analysis of the nucleocapsid of 14 HCV
      isolates failed to identify a sequence specifically associated with the
      development of steatosis. CONCLUSIONS: We provide virological and clinical
      evidence that the steatosis of the liver is the morphological expression of a
      viral cytopathic effect in patients infected with HCV genotype 3. At variance
      with published evidence from experimental models, the HCV nucleocapsid protein
      does not seem to fully explain the lipid accumulation in these patients.

PMID- 10905594
TI  - Hepatitis C virus infection and alanine transaminase levels in the general
      population: a survey in a southern Italian town.
AB  - BACKGROUND/AIM: The aim of the study was to estimate the prevalence, risk factors
      and genotype distribution of hepatitis C virus (HCV) in the general population
      older than 5 years of age in a southern Italian town. The positive predictive
      value of alanine transaminase (ALT) screening in identifying HCV positive
      subjects was also assessed. METHODS: Cluster random sampling from the census of
      the general population was used. ELISA and RIBA tests assessed the presence of
      anti-HCV; nested reverse transcription polymerase chain reaction (RT-PCR) was
      used to identify HCV-RNA; genotyping was performed by INNO-LIPA III. The
      association linking anti-HCV seropositivity with potential risk factors was
      assessed by multiple logistic regression analysis. RESULTS: Among the 488
      subjects enrolled, 79 (16.2%) were anti-HCV positive. The prevalence increased
      from 1.2% in subjects 6-29 years of age to 42.1% in those > or = 60 years. Forty
      percent of these positive subjects also had abnormal ALT level and 54.4% were HCV
      RNA positive by PCR. The positive predictive value of the ALT test in identifying
      anti-HCV positive subjects was 65%; however, it was 46.7% in subjects younger
      than 60 years of age and 90.5% in those 60 or older. Genotype 1b was detected in
      74% of subjects, type 2c in 23.3%, and type 1a in 2.3%. The only two variables
      significantly associated with HCV seropositivity in multivariate analysis were
      age older than 45 years (O.R. 8.5; CI 95%=3.0-24.1) and past use of glass
      syringes (O.R. 3.4; CI 95%=1.5-7.6). CONCLUSIONS: These findings confirm that HCV
      infection is endemic in southern Italy, particularly among the elderly.
      Percutaneous exposure, such as injections with nondisposable, multiple-use, glass
      syringes used in the past for medical purposes may have played a major role in
      the spread of HCV infection. ALT screening is not useful in detecting HCV
      positive subjects in the general population, particularly among subjects who
      could benefit from antiviral therapy.

PMID- 10905595
TI  - Impact of TT virus infection in acute and chronic, viral- and non viral-related
      liver diseases.
AB  - BACKGROUND/AIMS: The prevalence and pathogenicity of TT virus, recently
      identified in patients with non A-non G post-transfusional hepatitis, are
      questioned. METHODS: We investigated the impact of this new viral infection in a
      large series of patients with non A-non G, cryptogenic, non-viral and viral
      related, acute and chronic liver diseases (n=577) and blood donors (n=300). TTV
      DNA was detected in serum by hemi-nested polymerase chain reaction. Phylogenetic
      analysis was performed in 13 isolates. RESULTS: TTV DNA was detected in 6/25 and
      15/127 patients with cryptogenic non A-non G acute and chronic liver disease,
      respectively. TTV DNA positive subjects with post-transfusional acute hepatitis
      scored negative before transfusion. TTV prevalence was increased in patients with
      cryptogenic non A-non G acute and chronic liver disease compared to blood donors
      (6/300; p<0.001) and non-viral-related chronic liver diseases (6/137; p<0.05).
      TTV/HBV coinfection was frequently identified (35/147), but this was not the case
      for HCV-infected subjects (4/77). Transaminase activity or liver histological
      score was not significantly increased among TTV positive, HBV infected or non A
      non G patients. The HBV infection and Mediterranean origin were the risk factors
      associated with TTV infection. The majority of analysed sequences clustered in
      genotype 1 (8=1b; 3=1a). Two isolates showed homology to genotype 2. CONCLUSIONS:
      These results support the view that TTV is a widely spread infectious agent with
      a weak pathogenicity. It raises the possibility, however, that TTV might be
      implicated in a few cases of acute and chronic non A-non G hepatitis. TTV-DNA
      analysed sequences are related to genotypes 1 and 2 described in Europe.

PMID- 10905596
TI  - The pattern of response to interferon alpha (alpha-IFN) predicts sustained
      response to a 6-month alpha-IFN and ribavirin retreatment for chronic hepatitis
      C. TVVH Study Group.
AB  - BACKGROUND/AIMS: In chronic hepatitis C, interferon-alpha (alpha-IFN) and
      ribavirin combination therapy improves sustained response compared to alpha-IFN
      monotherapy, both in naive patients and in previous alpha-IFN relapsers, but the
      efficacy of such therapy remains limited in non-responder cases. The aim of this
      study was to assess whether the pattern of response to alpha-IFN alone may
      predict sustained response to combination therapy during retreatment. METHODS:
      Fifty previous alpha-IFN relapsers and 50 previous alpha-IFN non-responders were
      retreated with a high alpha-IFN dose (6 MU/thrice weekly for 2 months; induction
      phase) and then randomised to continue with alpha-IFN alone (3 MU/thrice weekly)
      or to receive combination therapy (3 MU/thrice weekly of alpha-IFN and 1000-1200
      mg/daily of ribavirin) for an additional 6 months according to the biochemical
      response to alpha-IFN shown after the induction phase. All patients were also
      evaluated for virological and histological response. RESULTS: Eleven of 25 (44%)
      relapsers treated with combination therapy and 4/25 (16%) treated with alpha-IFN
      alone achieved a sustained response. The corresponding figures among non
      responders were 1/25 (4%) and 0/25, respectively. Among 26 patients with a
      complete ALT and HCV-RNA response after 2 months of alpha-IFN, sustained response
      was seen in 11/14 (79%) treated with combination therapy and in 4/12 (33%)
      treated with alpha-IFN alone (p=0.05). On the other hand, of 74 cases still HCV
      RNA positive after 2 months of alpha-IFN alone, biochemical and virological end
      of therapy response was better with combination therapy (11/36; 30.5%) compared
      to alpha-IFN alone (4/38; 10.5%), but only one patient developed a sustained
      response (1/36; 3%). CONCLUSIONS: The retreatment with a 6-month combination
      therapy was associated with a high rate of sustained response only in patients
      showing a complete biochemical and virological response to alpha-IFN alone.
      Longer retreatment with combination therapy may be needed to achieve a sustained
      response in patients without a prompt virological response to alpha-IFN.

PMID- 10905597
TI  - Pre-treatment with prednisolone does not improve the efficacy of subsequent alpha
      interferon therapy in chronic hepatitis C.
AB  - BACKGROUND/AIMS: Alpha interferon administration is quite disappointing as a
      single therapy in chronic hepatitis C. A brief course of corticosteroid therapy
      might increase the effectiveness of subsequent alpha interferon administration,
      but data on this issue are controversial. METHODS: One hundred and fifty-six
      consecutive patients with chronic hepatitis C were randomly assigned to be
      treated blind with tapering doses of oral prednisolone or placebo for 4 weeks.
      Two weeks after cessation of therapy, patients received alpha interferon (3 MU
      t.i.w.) for 48 weeks and were followed for 24 additional weeks. Response was
      defined by the presence of normal alanine aminotransferase (ALT) and negative HCV
      RNA in serum. RESULTS: ALT activity decreased during prednisolone administration
      and rebounded upon withdrawal in 38% of the patients treated with this drug.
      Significant changes in serum bilirubin were not observed. HCV-RNA serum
      concentration tended to increase during prednisolone administration and to
      decrease upon withdrawal. ALT and HCV-RNA did not change during administration of
      placebo. At the end of interferon administration, 33% of patients treated with
      prednisolone and 25% of those treated with placebo presented biochemical and
      virological response. At the end of post-treatment follow-up, response was
      maintained in 12% and 13% of patients treated with prednisolone or placebo
      respectively. Response was not related to ALT or HCV-RNA changes observed during
      the pre-interferon phase of the study. No adverse events related to prednisolone
      administration were observed. CONCLUSIONS: Prednisolone administration and
      withdrawal induced a rebound in ALT activity and a decrease in HCV-RNA serum
      concentration in about one third of the patients with chronic hepatitis C.
      However, these changes did not enhance the effectiveness of subsequent alpha
      interferon therapy.

PMID- 10905599
TI  - Studies of genetic defects in hepatocellular carcinoma: recent outcomes and new
      challenges.

PMID- 10905598
TI  - Hammerhead ribozyme-mediated inhibition of hepatitis B virus X gene expression in
      cultured cells.
AB  - BACKGROUND/AIMS: Chronic infection with hepatitis B virus (HBV) is endemic to sub
      Saharan Africa and parts of Asia. Common complications of HBV persistence include
      cirrhosis and hepatocellular carcinoma (HCC). Present treatment of chronic HBV
      infection is usually ineffective and novel therapeutic approaches are an
      important objective. The HBV X protein (HBx) is a transcriptional activator that
      is required for the establishment of HBV infection and is implicated in
      hepatocarcinogenesis. The aim of this study was to assess the ability of two
      endogenously expressed hammerhead ribozymes to inhibit expression of HBV genes in
      transfected cultured cells. METHODS: Eukaryotic expression plasmids producing two
      ribozymes targeted to the HBx open reading frame, as well as their catalytically
      inactive homologues, were generated. Established cell lines and a primary culture
      of malignant hepatocytes were transfected to assess ribozyme effects on HBx
      expression and HBV replication. RESULTS: The ribozyme-expressing vectors inhibit
      expression of functional HBx protein and decrease HBV mRNA encoding surface and
      HBx sequences in transfected cells. Moreover, decreased HBsAg and HBeAg secretion
      from cells transfected with the ribozymes and an HBV replication competent
      plasmid provide evidence for an antireplicative effect of the ribozymes. However,
      the data do not exclude a dominant antisense effect that inhibits HBV gene
      expression. CONCLUSIONS: Inactivation of HBx, a sequence that is conserved in
      mammalian hepadnaviruses and found in all HBV transcripts, has potential for the
      treatment of chronic HBV infection.

PMID- 10905600
TI  - TT virus--highly prevalent, but still in search of a disease.

PMID- 10905601
TI  - Recurrent cholestatic jaundice associated with generalized pustular psoriasis:
      evidence for a neutrophilic cholangitis.
AB  - Generalized pustular psoriasis can result in systemic complications. We report
      the case of a woman with relapsing generalized pustular psoriasis and recurring
      episodes of cholestatic jaundice. Liver biopsy performed during an attack showed
      a neutrophilic infiltrate surrounding and invading portal triad bile ducts.
      Ultrasonographic exams and retrograde cholangiography ruled out biliary tract
      disease. This observation suggests that recurring cholestatic jaundice in
      pustular psoriasis is related to a neutrophilic cholangitis.

PMID- 10905603
TI  - Images in hepatology. Bone marrow deposits of oxalate crystals.

PMID- 10905602
TI  - Autoantibodies associated with acute rejection after liver transplantation for
      type-2 autoimmune hepatitis.
AB  - Autoantibodies, markers of autoimmune diseases, can also be detected in chronic
      allograft rejection. However, the appearance of these autoantibodies in acute
      rejection after orthotopic liver transplantation has not yet been reported. Liver
      kidney-microsome type-1 (LKM-1) antibodies directed against the autoantigen
      cytochrome CYP2D6 define a group of patients with autoimmune hepatitis type-2
      (AIH-2), distinct from autoimmune hepatitis type-1 (AIH-1) in which anti-nuclear
      antibodies and anti-smooth muscle antibodies (SMA) with actin specificity are
      present in patient sera. Autoantibodies were studied by the quantitative CYP2D6
      radioligand assay (RLA) that uses a radiolabeled CYP2D6 as antigen,
      immunoblotting using recombinant CYP2D6 protein and human liver microsomal and
      cytosolic fractions, and indirect immunofluorescence (IIF) using rat kidney
      stomach-liver cryostat sections. In addition, the specificity of anti-SMA was
      detected by IIF on HEp2 cell line harvested with colchicin. This report describes
      the time course of CYP2D6 antibodies and the appearance of anti-SMA (without anti
      actin, cytokeratin and vimentin reactivity) associated with acute rejection
      during a 2-year follow-up, in a patient who underwent transplantation at end
      stage type 2 autoimmune hepatitis. In addition, we report a new reactivity
      against an unknown 40-kDa protein using a rat cytosolic fraction. The detection
      of autoantibodies in sequential samples may be important to better predict
      rejection or relapse, and to establish adequate therapy.

PMID- 10905604
TI  - Predictive factors for failure to control bleeding in cirrhotic patients.

PMID- 10905605
TI  - Interleukin-12 production in chronic hepatitis C infection.

PMID- 10905606
TI  - The microfossil record of early land plants.
AB  - Dispersed microfossils (spores and phytodebris) provide the earliest evidence for
      land plants. They are first reported from the Llanvirn (Mid-Ordovician). More or
      less identical assemblages occur from the Llanvirn (Mid-Ordovician) to the late
      Llandovery (Early Silurian), suggesting a period of relative stasis some 40 Myr
      in duration. Various lines of evidence suggest that these early dispersed
      microfossils derive from parent plants that were bryophyte-like if not in fact
      bryophytes. In the late Llandovery (late Early Silurian) there was a major change
      in the nature of dispersed spore assemblages as the separated products of dyads
      (hilate monads) and tetrads (trilete spores) became relatively abundant. The
      inception of trilete spores probably represents the appearance of vascular plants
      or their immediate progenitors. A little later in time, in the Wenlock (early
      Late Silurian), the earliest unequivocal land plant megafossils occur. They are
      represented by rhyniophytoids. It is only from the Late Silurian onwards that the
      microfossil/ megafossil record can be integrated and utilized in interpretation
      of the flora. Dispersed microfossils are preserved in vast numbers, in a variety
      of environments, and have a reasonable spatial and temporal fossil record. The
      fossil record of plant megafossils by comparison is poor and biased, with only a
      dozen or so known pre-Devonian assemblages. In this paper, the early land plant
      microfossil record, and its interpretation, are reviewed. New discoveries, novel
      techniques and fresh lines of inquiry are outlined and discussed.

PMID- 10905607
TI  - The role of mid-palaeozoic mesofossils in the detection of early bryophytes.
AB  - Recently discovered Silurian and Devonian coalified mesofossils provide an
      additional source of data on early embryophytes. Those reviewed in this paper are
      considered of some relevance to understanding the early history of bryophytes
      while highlighting the difficulties of recognizing bryophytes in often very
      fragmentary fossils. The first group comprises sporophytes in which terminal
      sporangia contain permanent dyads and tetrads. Such spores (cryptospores) are
      similar to those found dispersed in older Ordovician and Silurian strata, when
      they are considered evidence for a land vegetation of embryophytes at a bryophyte
      grade. The phylogenetic significance of plants, where the axes associated with
      both dyad- and tetrad-containing sporangia are branching, a character state not
      found in extant bryophytes, is discussed. The second group comprises axial
      fossils, many with occasional stomata, in which central conducting strands
      include G-type tracheids and a number of novel types of elongate elements not
      readily compared with those of any tracheophyte. They include smooth-walled,
      evenly thickened elongate elements as well as those with numerous branching +/-
      anastomosing projections into the lumen. Some of the latter bear an additional
      microporate layer, but the homogenized lateral walls between adjacent cells are
      never perforate. Such cells, which occur in various combinations in central
      strands, are compared with the leptoids and hydroids of mosses, hydroids of
      liverworts and presumed water-conducting cells in coeval Lower Devonian plants
      such as Aglaophyton. It is concluded that lack of information on the chemistry of
      their walls hampers sensible assessment of their functions and the affinities of
      the plants. Finally, a minute fossil, comprising an elongate sporangium in which
      a central cylindrical cavity containing spores and possible elaters terminates in
      a complex poral dehiscence apparatus, is used to exemplify problems of
      identifying early bryophytes. It is concluded that further progress necessitates
      the discovery of pre-Upper Silurian fossils with well-preserved anatomy, as well
      as a re-evaluation of criteria used to assess existing and new Devonian fossils
      for bryophyte affinity.

PMID- 10905608
TI  - The origin of alternation of generations in land plants: a focus on matrotrophy
      and hexose transport.
AB  - A life history involving alternation of two developmentally associated,
      multicellular generations (sporophyte and gametophyte) is an autapomorphy of
      embryophytes (bryophytesphytes + vascular plants). Microfossil data indicate that
      Mid Late Ordovician land plants possessed such a life cycle, and that the origin
      of alternation of generations preceded this date. Molecular phylogenetic data
      unambiguously relate charophycean green algae to the ancestry of monophyletic
      embryophytes, and identify bryophytes as early-divergent land plants. Comparison
      of reproduction in charophyceans and bryophytes suggests that the following
      stages occurred during evolutionary origin of embryophytic alternation of
      generations: (i) origin of oogamy; (ii) retention of eggs and zygotes on the
      parental thallus; (iii) origin of matrotrophy (regulated transfer of nutritional
      and morphogenetic solutes from parental cells to the next generation); (iv)
      origin of a multicellular sporophyte generation; and (v) origin of non
      flagellate, walled spores. Oogamy, egg/zygote retention and matrotrophy
      characterize at least some modern charophvceans, and are postulated to represent
      pre-adaptative features inherited by embryophytes from ancestral charophyceans.
      Matrotrophy is hypothesized to have preceded origin of the multicellular
      sporophytes of' plants, and to represent a critical innovation. Molecular
      approaches to the study of the origins of matrotrophy include assessment of
      hexose transporter genes and protein family members and their expression
      patterns. The occurrence in modern charophyceans and bryophytes of chemically
      resistant tissues that exhibit distinctive morphology correlated with matrotrophy
      suggests that Early-Mid Ordovician or older microfossils relevant to the origin
      of land plant alternation of generations may be found.

PMID- 10905609
TI  - Vegetative and reproductive innovations of early land plants: implications for a
      unified phylogeny.
AB  - As the oldest extant lineages of land plants, bryophytes provide a living
      laboratory in which to evaluate morphological adaptations associated with early
      land existence. In this paper we examine reproductive and structural innovations
      in the gametophyte and sporophyte generations of hornworts, liverworts, mosses
      and basal pteridophytes. Reproductive features relating to spermatogenesis and
      the architecture of motile male gametes are overviewed and evaluated from an
      evolutionary perspective. Phylogenetic analyses of a data set derived from
      spermatogenesis and one derived from comprehensive morphogenetic data are
      compared with a molecular analysis of nuclear and mitochondrial small subunit
      rDNA sequences. Although relatively small because of a reliance on water for
      sexual reproduction, gametophytes of bryophytes are the most elaborate of those
      produced by any land plant. Phenotypic variability in gametophytic habit ranges
      from leafy to thalloid forms with the greatest diversity exhibited by hepatics.
      Appendages, including leaves, slime papillae and hairs, predominate in liverworts
      and mosses, while hornwort gametophytes are strictly thalloid with no organized
      external structures. Internalization of reproductive and vegetative structures
      within mucilage-filled spaces is an adaptive strategy exhibited by hornworts. The
      formative stages of gametangial development are similar in the three bryophyte
      groups, with the exception that in mosses apical growth is intercalated into
      early organogenesis, a feature echoed in moss sporophyte ontogeny. A
      monosporangiate, unbranched sporophyte typifies bryophytes, but developmental and
      structural innovations suggest the three bryophyte groups diverged prior to
      elaboration of this generation. Sporophyte morphogenesis in hornworts involves
      non-synchronized sporogenesis and the continued elongation of the single
      sporangium, features unique among archegoniates. In hepatics, elongation of the
      sporophyte seta and archegoniophore is rapid and requires instantaneous wall
      expandability and hydrostatic support. Unicellular, spiralled elaters and capsule
      dehiscence through the formation of four regular valves are autapomorphies of
      liverworts. Sporophytic sophistications in the moss clade include conducting
      tissue, stomata, an assimilative layer and an elaborate peristome for extended
      spore dispersal. Characters such as stomata and conducting cells that are shared
      among sporophvtes of mosses, hornworts and pteridophytes are interpreted as
      parallelisms and not homologies. Our phylogenetic analysis of three different
      data sets is the most comprehensive to date and points to a single phylogenetic
      solution for the evolution of basal embryophytes. Hornworts are supported as the
      earliest divergent embryophyte clade with a moss/liverwort clade sister to
      tracheophytes. Among pteridophytes, lycophytes are monophyletic and an assemblage
      containing ferns, Equisetum and psilophytes is sister to seed plants. Congruence
      between morphological and molecular hypotheses indicates that these data sets are
      tracking the same phylogenetic signal and reinforces our phylogenetic
      conclusions. It appears that total evidence approaches are valuable in resolving
      ancient radiations such as those characterizing the evolution of early
      embryophytes. More information on land plant phylogeny can be found at: http:
      //www.science.siu.edu/ landplants/index.html.

PMID- 10905610
TI  - Conducting tissues and phyletic relationships of bryophytes.
AB  - Internal specialized conducting tissues, if present, are restricted to the
      gametophytic generation in liverworts while they may occur in both generations in
      mosses. Conducting tissues are unknown in the anthocerotes. Water-conducting
      cells (WCCs) with walls perforated by plasmodesma-derived pores occur in the
      Calobryales and Pallaviciniaceae (Metzgeriales among liverworts and in Takakia
      among mosses. Imperforate WCCs (hydroids) are present in bryoid mosses. A
      polarized cytoplasmic organization and a distinctive axial system of microtubules
      is present in the highly specialized food-conducting cells of polytrichaceous
      mosses (leptoids) and in less specialized parenchyma cells of the leafy stem and
      seta in other mosses including Sphagnumn. A similar organization, suggested to
      reflect specialization in long-distance symplasmic transport of nutrients, also
      occurs in other parts of the plant in mosses, including rhizoids and caulonemata,
      and may be observed in thallus parenchyma cells of liverworts. Perforate WCCs in
      the Calobryales, Metzgeriales and Takakia, and hydroids in bryoid mosses,
      probably evolved independently Because of fundamental differences in
      developmental design, homology of any of these cells with tracheids is highly
      unlikely. Likewise, putative food-conducting of bryophytes present highly
      distinctive characteristics and cannot be considered homologous with the sieve
      cells of tracheophytes.

PMID- 10905611
TI  - Symbiotic fungal associations in 'lower' land plants.
AB  - An analysis of the current state of knowledge of symbiotic fungal associations in
      'lower' plants is provided. Three fungal phyla, the Zygomycota, Ascomycota and
      Basidiomycota, are involved in forming these associations, each producing a
      distinctive suite of structural features in well-defined groups of 'lower'
      plants. Among the 'lower' plants only mosses and Equisetum appear to lack one or
      other of these types of association. The salient features of the symbioses
      produced by each fungal group are described and the relationships between these
      associations and those formed by the same or related fungi in 'higher' plants are
      discussed. Particular consideration is given to the question of the extent to
      which root fungus associations in 'lower' plants are analogous to 'mycorrhizas'
      of 'higher' plants and the need for analysis of the functional attributes of
      these symbioses is stressed. Zygomycetous fungi colonize a wide range of extant
      lower land plants (hornworts, many hepatics, lycopods, Ophioglossales, Psilotales
      and Gleicheniaceae), where they often produce structures analogous to those seen
      in the vesicular-arbuscular (VA) mycorrhizas of higher plants, which are formed
      by members of the order Glomales. A preponderance of associations of this kind is
      in accordance with palaeohbotanical and molecular evidence indicating that
      glomalean fungi produced the archetypal symbioses with the first plants to emerge
      on to land. It is shown, probably for the first time, that glomalean fungi
      forming typical VA mycorrhiza with a higher plant (Plantago lanceolata) can
      colonize a thalloid liverwort (Pellia epiphylla), producing arbuscules and
      vesicles in the hepatic. The extent to which these associations, which are
      structurally analogous to mycorrhizas, have similar functions remains to be
      evaluated. Ascomycetous associations are found in a relatively small number of
      families of leafy liverworts. The structural features of the fungal colonization
      of rhizoids and underground axes of these plants are similar to those seen in
      mycorrhizal associations of ericaceous plants like Vaccinium. Cross inoculation
      experiments have confirmed that a typical mycorrhizal endophyte of ericaceous
      plants, Hymenoscyphus ericae, will form associations in liverworts which are
      structurally identical to those seen in nature. Again, the functional
      significance of these associations remains to be examined. Some members of the
      Jungermanniales and Metzgeriales form associations with basidiomycetous fungi.
      These produce intracellular coils of hyphae, which are similar to the pelotons
      seen in orchid mycorrhizas, which also involve basidiomycetes. The fungal
      associates of the autotrophic Aneura and of its heterotrophic relative
      Cryptothallus mirabilis have been isolated. In the latter case it has been shown
      that the fungal symbiont is an ectomycorrhizal associate of Betula, suggesting
      that the apparently obligate nature of the association between the hepatic and
      Betula in nature is based upon requirement for this particular heterotroph.

PMID- 10905612
TI  - Land plant biochemistry.
AB  - Biochemical studies have complemented ultrastructural and, subsequently molecular
      genetic evidence consistent with the Charophyceae being the closest extant algal
      relatives of the embryophytes. Among the genes used in such molecular
      phylogenetic studies is that rbcL) for the large subunit of ribulose bisphosphate
      carboxylase-oxygenase (RUBISCO). The RUBISCO of the embryophytes is derived, via
      the Chlorophyta. from that of the cyanobacteria. This clade of the molecular
      phylogeny of RUBISCO shows a range of kinetic characteristics, especially of CO2
      affinities and of CO2/O2 selectivities. The range of these kinetic values within
      the bryophytes is no greater than in the rest of the embryophytes; this has
      implications for the evolution of the embryophytes in the high atmospheric CO2
      environment of the late Lower Palaeozoic. The differences in biochemistry between
      charophycean algae and embryophytes can to some extent be related functionally to
      the structure and physiology of embryophytes. Examples of components of
      embryophytes, which are qualitatively or quantitatively different from those of
      charophytes, are the water repellent/water resistant extracellular lipids, the
      rigid phenolic polymers functional in water-conducting elements and mechanical
      support in air, and in UV-B absorption, flavonoid phenolics involved in UV-B
      absorption and in interactions with other organisms, and the greater emphasis on
      low Mr organic acids. retained in the plant as free acids or salts, or secreted
      to the rhizosphere. The roles of these components are discussed in relation to
      the environmental conditions at the time of evolution of the terrestrial
      embryophytes. A significant point about embryophytes is the predominance of
      nitrogen-free extracellular structural material (a trait shared by most algae)
      and UV-B screening components, by contrast with analogous components in many
      other organisms. An important question, which has thus far been incompletely
      addressed, is the extent to which the absence from bryophytes of the biochemical
      pathways which produce components found only in tracheophytes is the result of
      evolutionary loss of these functions.

PMID- 10905613
TI  - The relationships of vascular plants.
AB  - Recent phylogenetic research indicates that vascular plants evolved from
      bryophyte-like ancestors and that this involved extensive modifications to the
      life cycle. These conclusions are supported by a range of systematic data,
      including gene sequences, as well as evidence from comparative morphology and the
      fossil record. Within vascular plants, there is compelling evidence for two major
      clades, which have been termed lycophytes (clubmosses) and euphyllophytes (seed
      plants, ferns, horsetails). The implications of recent phylogenetic work are
      discussed with reference to life cycle evolution and the interpretation of
      stratigraphic inconsistencies in the early fossil record of land plants. Life
      cycles are shown to have passed through an isomorphic phase in the early stages
      of vascular plant evolution. Thus, the gametophyte generation of all living
      vascular plants is the product of massive morphological reduction. Phylogenetic
      research corroborates earlier suggestions of a major representational bias in the
      early fossil record. Mega-fossils document a sequence of appearance of groups
      that is at odds with that predicted by cladogram topology. It is argued here that
      the pattern of appearance and diversification of plant megafossils owes more to
      changing geological conditions than to rapid biological diversification.

PMID- 10905614
TI  - The origin and early evolution of tracheids in vascular plants: integration of
      palaeobotanical and neobotanical data.
AB  - Although there is clear evidence for the establishment of terrestrial plant life
      by the end of the Ordovician, the fossil record indicates that land plants
      remained extremely small and structurally simple until the Late Silurian. Among
      the events associated with this first major radiation of land plants is the
      evolution of tracheids, complex water-conducting cells defined by the presence of
      lignified secondary cell wall thickenings. Recent palaeobotanical analyses
      indicate that Early Devonian tracheids appear to possess secondary cell wall
      thickenings composed of two distinct layers: a degradation-prone layer adjacent
      to the primary cell wall and a degradation-resistant (possibly lignified) layer
      next to the cell lumen. In order to understand better the early evolution of
      tracheids, developmental and comparative studies of key basal (and potentially
      plesiomorphic) extant vascular plants have been initiated. Ultrastructural
      analysis and enzyme degradation studies of wall structure (to approximate
      diagenetic alterations of fossil tracheid structure) have been conducted on basal
      members of each of the two major clades of extant vascular plants: Huperzia
      (Lycophytina) and Equisetum (Euphyllophytina. This research demonstrates that
      secondary cell walls of extant basal vascular plants include a degradation-prone
      layer ('template layer') and a degradation-resistant layer ('resistant layer').
      This pattern of secondary cell wall formation in the water-conducting cells of
      extant vascular plants matches the pattern of wall thickenings in the tracheids
      of early fossil vascular plants and provides a key evolutionary link between
      tracheids of living vascular plants and those of their earliest fossil ancestors.
      Further studies of tracheid development and structure among basal extant vascular
      plants will lead to a more precise reconstruction of the early evolution of water
      conducting tissues in land plants, and will add to the current limited knowledge
      of spatial, temporal and cytochemical aspects of cell wall formation in tracheary
      elements of vascular plants.

PMID- 10905615
TI  - D-amino acids as putative neurotransmitters: focus on D-serine.
AB  - Of the twenty amino acids in the mammalian body, only serine and aspartate occur
      in D-configuration as well as L-configuration in significant amount. D-serine is
      selectively concentrated in the brain, localized to protoplasmic astrocytes that
      ensheath synapses and distributed similarly to N-methyl-D-aspartate (NMDA)
      subtype of glutamate receptors. D-serine has been found to function as an
      endogenous ligand for the "glycine" site of the NMDA receptor. Evidences for this
      include the greater potency of D-serine to activate this site than glycine, and D
      amino acid oxidase, which degrades D-serine as well as other neutral D-amino
      acids, markedly attenuates NMDA neurotransmission. D-serine is also formed by
      serine racemase, a recently cloned enzyme that converts L-serine to D-serine.
      Thus, in many ways D-serine fulfills criteria for defining its functionality as a
      neurotransmitter and challenges the dogma relating to neurotransmission, for it
      is the "unnatural" isomeric form of an amino acid derived from glia rather than
      neurons.

PMID- 10905616
TI  - Regulation of Myo-inositol homeostasis in differentiated human NT2-N neurons.
AB  - We have investigated the possible role of second messengers on inositol
      homeostasis in NT2-N cells, human central nervous system neurons obtained by
      terminal differentiation of teratocarcinoma precursors. Uptake of inositol into
      NT2-N neurons was inhibited approximately 10% by protein kinase C (PKC)
      activation but was unaffected by either the presence of cyclic nucleotide analogs
      or changes in the intracellular concentration of Ca2+. Efflux of inositol from
      NT2-N neurons was enhanced in hypotonic buffer but virtually eliminated by
      inclusion of the Cl- channel blocker 4,4'-diisothiocyanatostilbene-2,2'
      disulfonic acid, a result which indicates the involvement of a volume-sensitive
      organic osmolyte-anion channel. Volume-sensitive inositol efflux was stimulated
      approximately 30% following activation of PKC or elevation of the cytosolic Ca2+
      concentration but was unaffected by protein kinase A activation. These results
      suggest that whereas inositol uptake into NT2-N neurons is relatively refractory
      to regulation, volume-sensitive inositol efflux may be significantly affected by
      intracellular signaling events.

PMID- 10905617
TI  - Rapid and transient learning-associated increase in NMDA NR1 subunit in the rat
      hippocampus.
AB  - Several lines of evidence indicate that glutamate NMDA receptors are critically
      involved in long-term potentiation (LTP) and in certain forms of learning. It was
      previously demonstrated that memory formation of an inhibitory avoidance task in
      chick is specifically associated with an increase in the density of NMDA receptor
      in selected brain regions. Here we report on the effect of a one trial inhibitory
      avoidance training in rats, a hippocampal-dependent learning task, on the levels
      of different subunits of the glutamate NMDA receptor in synaptic plasma membranes
      (SPM) isolated from the hippocampus. Training rats on a one trial inhibitory
      avoidance task results in a rapid, transient and selective increase (+33%, p <
      0.05) in NMDA NRI subunit expression in hippocampal SPM of rats sacrificed 30 min
      posttraining. No changes were observed at 0 or 120 min after training or in
      shocked animals in comparison to naive control rats. In addition, no training
      associated increase in the levels of NMDA NR2A and NR2B or AMPA GluR 2/3 subunits
      was observed at any timepoint tested. In conclusion, the present findings support
      the hypothesis that alterations in expression of synaptic NMDA NR1 subunits in
      the hippocampus are specifically associated with memory formation of an
      inhibitory avoidance task and strongly suggest that hippocampal NMDA receptors
      are crucially involved in the neural mechanisms underlying certain forms of
      learning.

PMID- 10905618
TI  - Expression of lysophosphatidic acid receptor in rat astrocytes: mitogenic effect
      and expression of neurotrophic genes.
AB  - Lysophosphatidic acid (LPA) is a phospholipid mediator with a variety of
      biological activities. It remains unknown, however, which cells in the brain
      express the LPA receptor. The present study was undertaken to identify cells in
      the rat brain expressing functional LPA receptors, and to explore biological
      roles of LPA in these cells. We found that the LPA receptor was most dominantly
      expressed in rat astrocytes, determined by LPA-induced Ca2+ imaging, and by
      Northern blot analyses. LPA induced a mitogenic response and expression of
      immediate early genes in astrocytes, through pertussis-toxin sensitive G
      protein(s). LPA also stimulated the expression of various cytokine genes,
      including nerve growth factor, interleukin (IL)-1beta, IL-3 and IL-6. Thus,
      astrocytes are the major target of LPA in the brain. We propose that LPA may play
      important roles in neuronal development, gliosis and wound-healing process in the
      brain.

PMID- 10905619
TI  - The neuronal nicotinic acetylcholine receptor in some hereditary epilepsies.
AB  - Recent advances in human genetics and in the neurobiology of neurotransmitter
      receptors and channels have led to the discovery of specific genes associated
      with hereditary epileptic phenotypes. All the genes identified to date code for
      ligand- and voltage-gated ion channels. Some clinically rare idiopathic
      epilepsies are associated with mutations in genes coding for different neuronal
      nicotinic acetylcholine receptor (AChR) subunits. Distinct alpha subunits are
      found in the brain and in the peripheral nervous system, and structural, non
      alpha subunits like beta2 and beta4 confer different properties to neuronal
      receptors. Thus, the final properties of the oligomeric AChR depend on the
      different combinations of alpha and beta subunits. Most mutations found so far
      occur in the alpha4 chain, the most abundant subunit in the central nervous
      system. Specifically, the identification of mutations in the alpha4 subunit of
      neuronal AChR in human benign familial neonatal convulsions (BFNC) and autosomal
      dominant nocturnal frontal lobe epilepsy (ADNFLE) raise the possibility that the
      observed gene defects are linked (causatively) with these two diseases or,
      alternatively, that AChR alpha4 mutants increase the probability of epileptic
      discharges. We discuss testable hypotheses for unraveling the pathophysiology of
      these two disorders associated with AChR mutations.

PMID- 10905620
TI  - Searching for depolarization-induced genes that modulate synaptic plasticity and
      neurotrophin-induced genes that mediate neuronal differentiation.
AB  - We identify and characterize two classes of immediate-early genes: (i) genes,
      induced by depolarization in neurons, that play a role in depolarization-induced
      neuronal plasticity and (ii) genes, induced in neuronal precursors by
      neurotrophins, that play a causal role in neurotrophin-directed neuronal
      differentiation. We use rat PC12 pheochromocytoma cells to identify (i) genes
      preferentially induced by [depolarization or forskolin] versus [Nerve Growth
      Factor (NGF) or Epidermal Growth Factor (EGF)] and (ii) genes preferentially
      induced by NGF versus EGF. We describe (i) a collection of genes preferentially
      induced by depolarization/forskolin in PC12 cells and by kainic acid in vivo, and
      (ii) a collection of genes preferentially induced by NGF. The synaptotagmin IV
      gene encodes a synaptic vesicle protein whose level is modulated by
      depolarization. NGF preferentially induces the urokinase-plasminogen activator
      receptor in PC12 cells. Antisense oligonucleotide and anti-UPAR antibody
      experiments demonstrate that NGF-induced UPAR expression is required for NGF
      driven PC12 cell differentiation.

PMID- 10905621
TI  - Neuronal platelet-activating factor receptor signal transduction involves a
      pertussis toxin-sensitive G-protein.
AB  - In most nonneural systems, platelet-activating factor (PAF) receptor effects are
      mediated by G-proteins that are often pertussis toxin-sensitive. The activation
      of pertussis toxin-sensitive G-proteins linked to PAF receptors results in the
      mobilization of intracellular calcium, at least in part, through the second
      messenger inositol triphosphate. We have sought to determine if a pertussis toxin
      sensitive G-protein is involved in the PAF receptor-mediated phenomena of growth
      cone collapse and of synaptic enhancement in primary neuronal culture. Using
      infrared differential interference contrast microscopy and patch-clamp recording
      techniques, pertussis toxin, but not the inactive B oligomer of the toxin, was
      found to block both the growth cone collapse and the enhanced synaptic release of
      excitatory transmitter induced by a nonhydrolyzable PAF receptor agonist, making
      it likely that Go, Gq, or Gi is the G-protein transducer of PAF receptors in
      primary neurons. We believe that PAF acts directly on neuronal receptors, which
      are linked to pertussis toxin-sensitive G-proteins, on the tips of developing
      neurites, and on presynaptic nerve terminals, leading to growth cone collapse and
      enhanced synaptic release of transmitter.

PMID- 10905623
TI  - Differential role of hippocampal cAMP-dependent protein kinase in short- and long
      term memory.
AB  - One-trial step-down inhibitory (passive) avoidance training is followed by two
      peaks of cAMP-dependent protein kinase (PKA) activity in rat CA1: one immediately
      after training and the other 3 h later. The second peak relies on the first:
      Immediate posttraining infusion into CA1 of the inhibitor of the regulatory
      subunit of PKA, Rp-cAMPS, at a dose that reduces PKA activity during less than 90
      min, cancelled both peaks. Long-term memory (LTM) of this task measured at 24 h
      depends on the two peaks: Rp-cAMPS given into CA1 0 or 175 min posttraining, but
      not between those times, blocked LTM. However, the effect of immediate
      posttraining Rp-cAMPS on LTM could not be reversed by the activator of the
      regulatory subunit of PKA, Sp-cAMPS, given at 180 min, which suggests that, for
      LTM, the first peak may be more important than the second. When given at 0, 22,
      45, or 90, but not at 175 min from training, Rp-cAMPS blocked short-term memory
      (STM) measured at 90 or 180 min. This effect of immediate posttraining Rp-cAMPS
      infusion on STM but not that on LTM was readily reversed by Sp-cAMPS infused 22
      min later. On its own, Sp-cAMPS had effects exactly opposite to those of the
      inhibitor. It enhanced LTM when given at 0 or 175 min from training, and it
      enhanced STM when given at 0, 22, 45, or 90 min from training. These findings
      show that STM and LTM formation require separate PKA-dependent processes in CA1.
      STM relies on the continued activity of the enzyme during the first 90 min. LTM
      relies on the two peaks of PKA activity that occur immediately and 180 min
      posttraining.

PMID- 10905622
TI  - Platelet activating factor (PAF) antagonists on cytokine induction of iNOS and
      sPLA2 in immortalized astrocytes (DITNC).
AB  - Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine)
      and its receptor are known to play important roles in modulating neuronal
      plasticity and inflammatory responses, particularly during neuronal injury. PAF
      receptors are widespread in different brain regions and are present on the cell
      surface as well as in intracellular membrane compartments. Astrocytes are immune
      active cells and are responsive to cytokines, which stimulate signaling cascades
      leading to transcriptional activation of genes and protein synthesis. Our recent
      studies indicate the ability of cytokines, e.g., tumor necrosis factor-alpha
      (TNFalpha), interleukin-1beta (IL-1beta) and interferon-gamma (IFNgamma), to
      induce the inducible nitric oxide (iNOS) and secretory phospholipase A2 (sPLA2)
      genes in immortalized astrocytes (DITNC) (Li et al., J. Interferon and Cytokine
      Res. 19: 121-127. 1999). The main objective for this study is to examine the
      effects of PAF antagonists on cytokine induction of iNOS and sPLA2 in these
      cells. Results show that BN50730, a synthetic PAF antagonist, but not BN52021, a
      natural PAF antagonist (ginkolide B) can dose-dependently inhibit cytokine
      induction of NO production and sPLA2 release. Inhibition of NO production by
      BN50730 corroborated well with the decrease in iNOS protein and mRNA levels as
      well as binding of NF-kappaB STAT- 1 to DNA, suggesting that BN50730 action is
      upstream of the transcriptional process. These results are in agreement with the
      role of intracellular PAF in regulating the cytokine signaling cascade in
      astrocytes and further suggest the possible use of BN50730 as a therapeutic agent
      for suppressing the inflammatory pathways elicited by cytokines.

PMID- 10905624
TI  - Relationship between the ubiquitin-dependent pathway and apoptosis in different
      cells of the central nervous system: effect of thyroid hormones.
AB  - We have recently shown that sustained neonatal hyperthyroidism in the rat
      activates apoptosis of oligodendroglial cells (OLGc) and that inhibition of the
      proteasome-ubiquitin (Ub) pathway by lactacystin produces increased apoptosis in
      cerebellar granule cells (CGC). In the present study we have analyzed the
      relationship between the activation of the Ub-dependent pathway, the expression
      of the Ub genes and programmed cell death in neurons of the rat cerebellum and
      cerebral cortex and in OLGc. This study was carried out in normal animals, in
      rats submitted to sustained neonatal hyperthyroidism and in cell cultures treated
      with an excess of thyroid hormones. In neurons of the cerebral cortex, thyroid
      hormone produces an increase of Ub-protein conjugates, an enhancement in the
      expression of the Ub genes and an increase in apoptosis, while the opposite
      results are obtained in CGC. These results indicate that in neurons, the changes
      in the cell death program produced by thyroid hormone run in parallel with those
      occurring in the Ub-dependent pathway. In OLGc, thyroid hormone increases
      apoptosis but does not produce changes in the Ub pathway. Preliminary studies
      indicate that in coincidence with what occurs in optic nerves, the sciatic nerves
      both in controls and in hyperthyroid animals are unable to form Ub-protein
      conjugates. These results indicate that in cells of the CNS such as neurons, in
      which the Ub-dependent pathway is actively expressed, it appears to be closely
      correlated with apoptosis.

PMID- 10905625
TI  - Ligand binding to CNS muscarinic receptor is transiently modified by convulsant 3
      mercaptopropionic acid administration.
AB  - The administration of convulsant drugs has proven a powerful tool to study
      experimental epilepsy. We have already reported that the administration of
      convulsant 3-mercaptopropionic acid (mp) at 150 mg/kg enhances binding affinity
      of muscarinic antagonist [3H]quinuclidinyl benzilate ([3H]QNB) to certain rat CNS
      membranes during seizure and postseizure without affecting site number. Results
      obtained with a 100-mg/kg dose of mp have shown reversible increases in [3H]QNB
      binding to cerebellum and hippocampus, whereas a delayed response has been found
      in striatum. Neither a subconvulsant dose nor in vitro addition modifies binding.
      In order to evaluate preseizure, seizure as well as early (30 min) and late (24
      h) postseizure stages, we employed a 50 mg/kg dose and tested [3H]QNB binding to
      CNS membranes. Changes in binding were as follows (in %): in cerebellum, +37,
      +86, and +40 at preseizure, seizure and early postseizure stages, respectively,
      but there was a decrease at late postseizure; in hippocampus, +27 at pre- and
      seizure stages, but a decrease at early and late postseizure. No changes were
      found in striatum or cerebral cortex membranes at any stage studied. Saturation
      curves analysed by Scatchard plots indicated that changes in [3H]QNB binding to
      cerebellar membranes are attributable to an increase in ligand affinity at
      seizure, followed by a decrease in binding site number at postseizure. A similar
      profile was observed for hippocampus except that the decrease in binding site
      number, though lower than at postseizure, was already evident at seizure stage.
      Results confirm a region-specific response to the convulsant and transient
      changes provide an example of neuronal plasticity.

PMID- 10905626
TI  - Spreading depression-induced cyclooxygenase-2 expression in the cortex.
AB  - Spreading depression (SD) is a wave of sustained depolarization challenging the
      energy metabolism of the cells without causing irreversible damage. However,
      brain injury, especially focal ischemic stroke, triggers SD-like waves, which in
      the vicinity of the original damage site contribute to enlargement of the dying
      brain tissue. Brain injury induces expression of several genes, which are thought
      to play a role in neuronal death, and therefore represent potential targets for
      therapy. One such gene is cyclooxygenase-2 (COX-2), an inducible prostaglandin
      and superoxide producing enzyme. Here we review our recent studies on the
      regulation of COX-2 in SD.

PMID- 10905627
TI  - Alzheimer's Abeta1-40 peptide modulates lipid synthesis in neuronal cultures and
      intact rat fetal brain under normoxic and oxidative stress conditions.
AB  - The effect of amyloid beta (Abeta), the major constituent of the Alzheimer's (AD)
      brain on lipid metabolism was investigated in cultured nerve cells and in a fetal
      rat brain model. Differentiated (NGF) and undifferentiated PC12 cells or primary
      cerebral cell cultures were incubated with [14C]acetate in the absence or
      presence of Abeta1-40. Incorporation of label into lipid species was determined
      after lipid extraction and TLC separation. Phosphatidylcholine (PC) and
      phosphatidylserine (PS) synthesis was increased by Abeta1-40, in a dose dependent
      manner, an effect which was more pronounced in differentiated PC12 cells. A
      significant proportion of radioactivity (5-6%) was released into the medium with
      a radioactivity distribution similar to that of the cellular lipids. Cholesterol
      and PC were the highest labeled medium lipids. Increasing Abeta1-40 concentration
      up to 0.1 microg/ml in cerebral cells but not in PC12 cells, caused a relative
      increase (1.5 fold) in release of PS, while that of PE decreased. Stimulation of
      PS release may possibly be associated with apoptotic cell death. Abeta1-40
      peptide (5 microg) was administered intraperitoneally into rat fetuses (18 days
      gestation) along with [14C]acetate (2 microCi/fetus). After 24 h, the maternal
      fetal blood supply was occluded for 20 min (ischemia) followed by 15 min
      reperfusion. Fetuses were killed and liver and brain tissue subjected to lipid
      extraction and radioactivity determination after TLC. Abeta1-40 peptide increased
      synthesis of different classes of lipids up to 20-40% in brain tissue compared to
      controls. Labeling of liver lipids was decreased by Abeta1-40 by 20-30%. A
      general decrease in synthesis of lipids was observed after ischemia/reperfusion.
      Our data suggest that Abeta1-40 peptide regulates normal lipid biosynthesis but
      under ischemia it compromises it. The latter finding may confirm the oxidative
      stress etiology in AD and suggests that Abeta1-40 modulation of lipid metabolism
      may have Alzheimer's pathological relevance, particularly at high peptide
      concentrations.

PMID- 10905628
TI  - Is neuronal injury caused by hypoglycemic coma of the necrotic or apoptotic type?
AB  - In this study, we explored if a 30 minute period of hypoglycemic coma yields
      damage which shows some features associated with apoptosis. To that end, we
      induced insulin-hypoglycemic coma of 30 min duration, and studied brain tissues
      after the coma period, and after recovery period of 30 min, 3 h, and 6 h.
      Histopathological data confirmed neuronal damage in all of the vulnerable
      neuronal populations. Release of cytochrome c (cyt c), assessed by Western Blot,
      was observed in the neocortex and caudoputamen after 3 and 6 h of recovery. In
      these regions, the caspase-like activity increased above control after 6 h of
      recovery. By laser-scanning confocal microscopy, a clear expression of Bax was
      observed after 30 min of coma in the superficial layers of the neocortex,
      reaching a peak after 30 min of recovery. Punctuate immunolabeling surrounding
      nuclei in soma and dendrites in cortical pyramidal neurons likely represents
      mitochondria, which suggests that Bax protein assembled at the surface of
      mitochondria in vulnerable neocortical neurons. It is concluded that although
      previous morphological data have suggested that cells die by necrosis, neuronal
      damage after hypoglycemic coma shows some features of apoptosis.

PMID- 10905629
TI  - The cytoskeletal components of the myelin fraction are affected by a single
      intracranial injection of apotransferrin in young rats.
AB  - We have previously shown that in rat pups intracranially injected with a single
      dose of apotransferrin (aTf), there is an early oligodendroglial cell OLGc
      differentiation. The expression of the mRNAs of myelin basic proteins and of
      2',3' cyclic nucleotide 3'-phosphodiesterase and the amount of the corresponding
      proteins, as well as myelin glycolipids and phospholipids, were significantly
      increased in these animals at 10 and 17 days of age. Microtubules and myelin
      basic proteins appear to be closely associated in OLGc and it has been shown that
      the mRNAs of myelin basic proteins are concentrated in the OLGc processes. The
      aim of this work was to clarify if the accelerated myelination produced by aTf
      could be linked to changes in certain cytoskeletal elements present in the myelin
      fraction such as tubulin, actin, and different microtubule-associated proteins
      (MAPs). A significant increase in the expression of the mRNA of tubulin and actin
      was observed in the brain of the aTf-treated animals. Several MAPs, particularly
      MAP 1B and stable tubule only peptide as well as actin and tubulin, were markedly
      increased in the Triton X-100 insoluble pellet obtained from the myelin fraction
      of these animals. The changes that we have previously described in the myelin of
      aTf intracranially injected rats, could be the consequence of its action on the
      cytoskeletal network of the OLGc. An enlargement of this structure would result
      in a more efficient and faster movement of the different components that are
      normally transported to the myelin by the cytoskeleton of this cell.

PMID- 10905630
TI  - Lipid acetylation reactions and the metabolism of platelet-activating factor.
AB  - In this review properties of lipid acetyltransferase enzymes are outlined. The
      three activities of interest are lyso PAF acetyltransferase (acetyl CoA: 1-alkyl
      sn-glycero-3-phosphocholine acetyltransferase), AGP acetyltransferase (acetyl
      CoA: 1-alkyl sn-glycero-3-phosphate acetyltransferase) and a transacetylase
      activity that can transfer acetyl groups from PAF to lipid acceptors in the
      formation of 1-alkenyl-2-acetyl-sn-glycero-3-phosphoethanolamine and N-acetyl
      sphingosine (C2 ceramide). This review focuses on the role of acetyltransferases
      and transacetylases within the metabolism of platelet-activating factor and
      specifically addresses characteristics of the enzymes, including subcellular
      localization, substrate selectivity, and enzymatic regulation.

PMID- 10905631
TI  - Retinal structure and function in an animal model that replicates the biochemical
      hallmarks of desmosterolosis.
AB  - Desmosterolosis is a rare, autosomal recessive, human disease characterized by
      multiple congenital anomalies in conjunction with grossly elevated levels of
      desmosterol and markedly reduced levels of cholesterol in all bodily tissues.
      Herein, we evaluated retinal sterol composition, histology, and
      electrophysiological function in an animal model that exhibited the biochemical
      features of desmosterolosis, produced by treating pregnant rats and their progeny
      with U18666A, an inhibitor of desmosterol reductase. Treated rats had cataracts,
      were substantially smaller, and had markedly high levels of desmosterol and
      profoundly low levels of cholesterol in their retinas and other tissues compared
      to age-matched controls. However, their retinas were histologically normal and
      electrophysiologically functional. These results suggest that desmosterol may be
      able to replace cholesterol in the retina, both structurally and functionally.
      These findings are discussed in the context of "sterol synergism".

PMID- 10905632
TI  - Strong association of unesterified [3H]docosahexaenoic acid and [3H
      docosahexaenoyl]phosphatidate to rhodopsin during in vivo labeling of frog
      retinal rod outer segments.
AB  - Docosahexaenoic acid (DHA, 22:6n-3), the most prevalent fatty acid in
      phospholipids of rod outer segments (ROS), is essential for visual transduction
      and daily renewal of ROS membranes. We investigated the association of [3H]DHA
      lipids to rhodopsin in ROS from frogs (Rana pipiens) after in vitro (4 hrs) and
      in vivo (1 day and 32 days) labeling. Lipids from lyophilized ROS were
      sequentially extracted with hexane (neutral lipids), chloroform:methanol
      (phospholipids) and acidified chloroform:methanol (acidic phospholipids). After
      in vitro labeling, free [3H]DHA was easily extracted with hexane (66% of total
      ROS free DHA), implying a weak association with proteins (rhodopsin). In
      contrast, after in vivo labeling free [3H]DHA was mainly recovered in the acidic
      solvent extract (89-99%). Of all phospholipids, [3H-DHA]phosphatidic acid (PA)
      displayed the highest binding to rhodopsin after both in vitro (43% in acidic
      extract) and in vivo (>70%) labeling suggesting a possible modulatory role of
      free DHA and DHA-PA in visual transduction.

PMID- 10905633
TI  - Properties and regulation of microsomal PAF-synthesizing enzymes in rat brain
      cortex.
AB  - Platelet-activating factor (PAF) is a phospholipid mediator of long-term
      potentiation, synaptic plasticity and memory formation as well as of the
      development of brain damage. In brain, PAF is synthesized by two distinct
      pathways but their relative contribution to its productions, in various
      physiological and pathological conditions, is not established. We have further
      investigated on the properties of the two enzymes that catalyze the last step of
      the de novo or remodeling pathways in rat brain microsomes, PAF-synthesizing
      phosphocholinetransferase (PAF-PCT) and lysoPAF acetyltransferase (lysoPAF-AT),
      respectively. The latter enzyme is fully active at microM Ca2+ concentration,
      inhibited by MgATP and activated by phosphorylation. Because the reversibility of
      the reaction catalyzed by PAF-PCT, its direction depends on the ratio [CDP
      choline]/[CMP], which is related to the energy charge of the cell. These and
      other properties indicate that the de novo pathway should mainly contribute to
      PAF synthesis for maintaining its basal levels under physiological conditions.
      The remodeling pathway should be more involved in the production of PAF during
      ischemia. During reperfusion, the overproduction of PAF should be the result of
      the concomitant activation of both pathways.

PMID- 10905635
TI  - GM1 synthase depends on N-glycosylation for enzyme activity and trafficking to
      the Golgi complex.
AB  - Glycosyltransferase cDNAs contain a variable number of potential N-glycosylation
      sites. Here we examined the occupancy and relevance for the activity and
      intracellular trafficking of the only potential N-glycosylation site of the mouse
      beta1,3galactosyltransferase (Gal-T2 or GA1/GM1/GD1b synthase) in Gal-T2 cDNA
      transfected CHO-K1 cells. Transfected cells synthesize a Golgi located active
      enzyme of 43 kDa whose N-glycan was metabolically labeled from [3H]mannose and
      was Endo-H sensitive. Inhibition of N-glycosylation by Tunicamycin or by point
      mutation of the N-glycosylation site resulted in the synthesis of a polypeptide
      of 40 kDa which lacked enzyme activity and was concentrated in the endoplasmic
      reticulum (ER). Inhibition of ER glucosidases by Castanospermine impaired the
      exit of a form of Gal-T2 having reduced enzyme activity from the ER. The N
      terminal Gal-T2 domain (aa 1-52) was able to direct and to retain the green
      fluorescence protein in the Golgi complex. Taken together, these results indicate
      that Gal-T2 depends on N-glycosylation for its activity and for proper
      trafficking to, but not its retention in, the Golgi complex.

PMID- 10905634
TI  - Uptake and incorporation of docosahexaenoic acid (DHA) into neuronal cell body
      and neurite/nerve growth cone lipids: evidence of compartmental DHA metabolism in
      nerve growth factor-differentiated PC12 cells.
AB  - Docosahexaenoic acid (DHA) accumulates in nerve endings of the brain during
      development. It is released from the membrane during ischemia and
      electroconvulsive shock. DHA optimizes neurologic development, it is
      neuroprotective, and rat adrenopheochromocytoma (PC12) cells have decreased PLA2
      activity when DHA is present. To characterize DHA metabolism in PC12 cells, media
      were supplemented with [3H]DHA or [3H]glycerol. Fractions of nerve growth cone
      particles (NGC) and cell bodies were prepared and the metabolism of the
      radiolabeled substrates was determined by thin-layer chromatography. [3H]glycerol
      incorporation into phospholipids indicated de novo lipid synthesis. [3H]DHA
      uptake was more rapid in the cell bodies than in the NGC. [3H]DHA first
      esterified in neutral lipids and later in phospholipids
      (phosphatidylethanolamine). [3H]glycerol primarily labeled phosphatidylcholine.
      DHA uptake was compartmentalized between the cell body and the NGC. With
      metabolism similar to that seen in vivo, PC12 cells are an appropriate model to
      study DHA in neurons.

PMID- 10905636
TI  - Identification of mu-class glutathione transferases M2-2 and M3-3 as cytosolic
      prostaglandin E synthases in the human brain.
AB  - Cytosolic prostaglandin (PG) E synthase was purified from human brain cortex. The
      N-terminal amino acid sequence, PMTLGYXNIRGL, was identical to that of the human
      mu-class glutathione transferase (GST) M2 subunit. Complementary DNAs for human
      GSTM2, GSTM3, and GSTM4 subunits were cloned, and recombinant proteins were
      expressed as homodimers in Escherichia coli. The recombinant GSTM2-2 and 3-3
      catalyzed the conversion of PGH2 to PGE2 at the rates of 282 and 923 nmol/min/mg
      of protein, respectively, at the optimal pH of 8, whereas GSTM4-4 was inactive;
      although all three enzymes showed GST activity. The PGE synthase activity
      depended on thiols, such as glutathione, dithiothreitol, 2-mercaptoethanol, or L
      cysteine. Michaelis-Menten constants and turnover numbers for PGH2 were 141
      microM and 10.8 min(-1) for GSTM2-2 and 1.5 mM and 130 min(-1) for GSTM3-3,
      respectively. GSTM2-2 and 3-3 may play crucial roles in temperature regulation,
      nociception, and sleep-wake regulation by producing PGE2 in the brain.

PMID- 10905637
TI  - Regulation of phospholipase C activity by calcium ions and guanine nucleotide in
      the normoxic cat carotid body.
AB  - The carotid bodies (CB) are a paired chemoreceptor organ located at the
      bifurcation of the common carotid arteries. High O2 tension suppresses while low
      tension activates afferent carotid chemoreceptor activity and the chemoreflex
      ventilatory response in the cat. The intracellular mechanism of chemotransduction
      is till now unknown. Previously we have shown different activities of
      phospholipase C (PLC) in normoxic, hypoxic and hyperoxic cat carotid body. Now we
      have addressed the question whether calcium ions and G-protein could be
      regulators of the formation of lipid derived messenger molecules in the cat
      carotid body. To answer this question, the PLC acting against [3H] inositol
      phosphatidylinositol (PtdIns) and [3H] inositol-phosphatidylinositol-4,5
      bisphosphate [PtdIns(4,5)P2] in the cat CB were investigated using labelled
      phospholipids as a source of the substrate. CB homogenate was used as a source of
      the enzyme. The results indicate that PLC acting on PtdIns is Ca2+-dependent, in
      contrary to that acting on PtdIns(4,5)P2 which remains active in the presence of
      10 mM EGTA. PtdIns(4,5)P2-PLC is stimulated by GTPgammaS. In the presence of
      Ca2+, GTPgammaS has a synergistic stimulatory effect. PLC acting on PtdIns is not
      activated by GTPgammaS. In the presence of calcium ions dopamine and a
      nonhydrozylable analogue of acetylcholine, carbachol, have a small stimulatory
      effect of about 30% on PLC acting on PtdIns(4,5)P2. GTPgammaS enhances this
      effect. These results allow us to suggest that there are two pathways of
      phosphoinositides degradation in the CB, one of them is regulated by calcium
      ions/PtdIns-PLC/, the other one by G-protein / PtdIns(4,5)P2-PLC/.

PMID- 10905639
TI  - Alveolar dead space as a predictor of severity of pulmonary embolism.
AB  - OBJECTIVE: To determine whether the alveolar dead space volume (V(D)alv),
      expressed as a percentage of the alveolar tidal volume (V(D)alv/V(T)alv), can
      predict the degree of vascular occlusion caused by pulmonary embolism (PE).
      METHODS: Fifty-three subjects with suspected PE were prospectively studied.
      Pulmonary embolism was diagnosed in 33 by high-probability ventilation/perfusion
      (V/Q) scan (n = 19) or by pulmonary arteriography (PAG, n = 14). Pulmonary
      embolism was excluded by PAG in 20 subjects. The V(D)alv/V(T)alv was determined
      from volumetric capnography and arterial blood gas analysis, which permits
      measurement of the physiologic dead space, V(D)phys (mL) = [(PaCO2 -
      PeCO2)/PaCO2]. tidal volume. Airway dead space (V(D)aw) was subtracted to yield
      the alveolar dead space [(V(D)phys - V(D)aw) = V(D)alv (mL)]; the percentage of
      alveolar volume occupied by alveolar dead space per breath = V(D)alv/V(T)alv x
      100%. Percentage perfusion defect was determined from V/Q scans by a radiologist
      blinded to other data. Regression analysis was performed to show correlation
      between V(D)alv/V(T)alv and defect on V/Q scan or systolic pulmonary arterial
      pressure (SPAP). RESULTS: For subjects with PE, the mean perfusion defect on lung
      scan was 38 +/- 22%; the mean V(D)alv = 208 +/- 115 mL, V(T)alv = 452 +/- 251 mL,
      and V(D)alv/V(T)alv = 43 +/- 18%. Regression of V(D)alv/V(T)alv vs perfusion
      defect yielded r2 = 0.41. Regression of V(D)alv/V(T)alv vs pulmonary artery
      pressures yielded r2 = 0.59. For subjects without PE, V(D)alv/V(T)alv = 27 +/-
      14% and V(D)alv = 89 +/- 66 mL. CONCLUSIONS: The V(D)alv/V(T)alv correlates with
      the lung perfusion defect and the pulmonary artery pressures in subjects with PE.
      These findings show the potential for V(D)alv/V(T)alv to quantify the embolic
      burden of PE.

PMID- 10905640
TI  - Antagonism of the cardiodepressant effects of adenosine during acute hypoxia.
AB  - OBJECTIVE: To determine whether pharmacologic antagonism of adenosine A1-receptor
      mediated cardiovascular changes can improve cardiac function and prolong survival
      during systemic hypoxia. METHODS: Rats were anesthetized with ketamine,
      instrumented [including left ventricular (LV) pressure transducing catheters],
      paralyzed with vecuronium, then ventilated to pCO2 = 35-40 torr. After 10 minutes
      of equilibration (baseline), treatment commenced with saline (n = 7), NPC-205, an
      adenosine A1 receptor selective antagonist, at doses of 1 mg/kg (n = 10) or 10
      mg/kg (n = 10), or drug vehicle (n = 9). Ten minutes later, inspired oxygen was
      reduced to 5%. RESULTS: Survival duration (min) post-hypoxia increased in a dose
      dependent fashion from 10.4 +/- 1.4 (mean +/- SEM) with vehicle control to 23.0
      +/- 4.7 and 41.1 +/- 5.7 with 1 and 10 mg/kg NPC-205, respectively (p < 0.000).
      Five minutes post-hypoxia, dose-dependent increases were also seen in the
      percentage of pre-hypoxic values of LV contractility [25.9 +/- 8.1 (vehicle),
      39.5 +/- 9.6 (1 mg/kg NPC-205), and 56.5 +/- 8.7 (10 mg/kg NPC-205), p = 0.01],
      heart rate [60.6 +/- 8.3 (vehicle), 74.7 +/- 8.2 (1 mg/kg NPC-205), and 90.4 +/-
      24.1 (10 mg/kg NPC-205), p = 0.02], and blood pressure [16.1 +/- 4.8 (vehicle),
      28.8 +/- 8.6 (1 mg/kg NPC-205), and 51.7 +/- 8.2 (10 mg/kg NPC-205), p = 0.004].
      CONCLUSIONS: The adenosine A1 selective antagonist prolonged survival in this
      model. This prolongation was attributed to inhibition of adenosine A1 receptor
      mediated decline in cardiac inotropy and chronotropy. Adenosine A1 receptor
      selective antagonists show promise as adjunctive therapy for hypoxia-induced
      cardiac insufficiency by prolonging the treatment window until more definitive
      resuscitation measures are taken.

PMID- 10905638
TI  - Phospholipases A2 in ischemic and toxic brain injury.
AB  - Phospholipases A2 (PLA2s) regulate hydrolysis of fatty acids, including
      arachidonic acid, from the sn-2 position of phospholipid membranes. PLA2 activity
      has been implicated in neurotoxicity and neurodegenerative processes secondary to
      ischemia and reperfusion and other oxidative stresses. The PLA2s constitute a
      superfamily whose members have diverse functions and patterns of expression. A
      large number of PLA2s have been identified within the central nervous systems of
      rodents and humans. We postulated that group IV large molecular weight, cytosolic
      phospholipase A2 (cPLA2) has a unique role in neurotoxicity associated with
      ischemic or toxin stress. We created mice deficient in cPLA2 and tested this
      hypothesis in two injury models, ischemia/reperfusion and MPTP neurotoxicity. In
      each model cPLA2 deficient mice are protected against neuronal injury when
      compared to their wild type littermate controls. These experiments support the
      hypothesis that cPLA2 is an important mediator of ischemic and oxidative injuries
      in the brain.

PMID- 10905641
TI  - Myoglobin for early risk stratification of emergency department patients with
      possible myocardial ischemia.
AB  - OBJECTIVES: To determine and compare the prognostic abilities of early, single
      sample myoglobin measurement with that of creatine kinase-MB (CK-MB), with
      cardiac troponin T (cTnT), and with physician judgment in the absence of marker
      results among emergency department (ED) patients with possible myocardial
      ischemia. METHODS: Prospective collection of clinical and serologic data using an
      identity-unlinked technique from patients with possible myocardial ischemia at
      two urban EDs. Outcome data concerning the occurrence of adverse events (AEs)
      during the 14 days after enrollment were used to calculate and compare the
      relative risks (RRs) and predictive values (with 95% confidence intervals) of the
      various markers for predicting AEs. RESULTS: Among 396 analyzed patients, 65
      (16.4%) accrued 104 AEs, including 13 deaths (3.3%) and 31 (7.8%) myocardial
      infarctions. Myoglobin predicted AEs (RR = 3.36 [95% CI = 2.19 to 5.15]) with
      significantly higher sensitivity (50.8% [95% CI = 38.6 to 62.9]) than either CK
      MB (15.4% [95% CI = 6.6 to 24.2]) or cTnT (24.6% [95% CI = 14.1 to 35.1]), but
      with lower specificity (81.9% [95% CI = 77.7 to 86.0]; CK-MB = 99.7% [95% CI =
      99.1 to 100]; cTnT = 93.1% [95% CI = 90.3 to 95.8]). Myoglobin had prognostic
      ability among patients with chest pain (3.86 [95% CI = 2.39 to 6.22]) and
      atypical (non-chest pain) presentations (2.71 [95% CI = 1.09 to 6.71]), including
      those with a nondiagnostic electrocardiogram (3.11 [95% CI = 1.44 to 6.69]). The
      combination of myoglobin and physician decision making identified 63 of the 65
      patients (96.9% [95% CI = 92.7 to 100]) with subsequent AEs. CONCLUSIONS: The
      early prognostic sensitivity of myoglobin may allow identification of some high
      risk patients missed by physician judgment, CK-MB, and cTnT. Myoglobin should be
      considered for use in the ED based on both its diagnostic and prognostic
      abilities.

PMID- 10905642
TI  - Epidemiologic analysis of an urban, public emergency department's frequent users.
AB  - OBJECTIVES: To determine how the demographic, clinical, and utilization
      characteristics of emergency department (ED) frequent users differ from those of
      other ED patients. METHODS: A cross-sectional and retrospective cohort study was
      performed using a database of all 348,858 visits to the San Francisco General
      Hospital ED during a five-year period (July 1, 1993, to June 30, 1998). A
      "frequent user" visited the ED five or more times in a 12-month period. RESULTS:
      Frequent users constituted 3.9% of ED patients but accounted for 20.5% of ED
      visits. The relative risk (RR) of frequent use was high among patients who were
      homeless (RR = 4.5), African American (RR = 1.8), and Medi-Cal sponsored (RR =
      2.1). Frequent users were more likely to be seen for alcohol withdrawal (RR =
      4.4), alcohol dependence (RR = 3.4), and alcohol intoxication (RR = 2.4).
      Frequent users were also more likely to visit for exacerbations of chronic
      conditions, including sickle cell anemia (RR = 8.0), renal failure (RR = 3.6),
      and chronic obstructive pulmonary disease (RR = 3.3). They were less likely to
      visit for all forms of trauma (RR = 0.43). Survival analysis showed that only 38%
      of frequent users for one year remained frequent users the next year. However,
      56% of frequent users for two consecutive years remained frequent users in the
      third year. CONCLUSIONS: Frequent use of the ED reflects the urban social
      problems of homelessness, poverty, alcohol abuse, and chronic illness. Frequent
      use of the ED shows a high rate of decline from one year to the next. This rate
      of decline slows after the first year and suggests the existence of a smaller
      group of chronic frequent users.

PMID- 10905643
TI  - Continuous electrocardiographic monitoring and cardiac arrest outcomes in 8,932
      telemetry ward patients.
AB  - OBJECTIVE: To estimate the benefit of routine electrocardiographic (ECG)
      telemetry monitoring on in-hospital cardiac arrest survival. METHODS: In a
      tertiary care hospital, all telemetry ward admissions and cardiac arrests
      occurring over a five-year period were reviewed. Ward location and survival to
      discharge were determined for all patients outside of critical care areas.
      RESULTS: During the study period, 8,932 patients were admitted to the telemetry
      ward, and 20 suffered cardiac arrest (0.2%; 95% CI = 0.1 to 0.3). Telemetry
      monitors signaled the onset of cardiac arrest in only 56% (95% CI = 30 to 80) of
      monitored arrests. Three patients survived to discharge, and in two of these
      three patients the arrest onset was signaled by the monitor. This yields a
      monitor-signaled survival rate among telemetry ward patients of 0.02% (95% CI = 0
      to 0.05). All survivors suffered significant arrhythmias prior to their cardiac
      arrests. CONCLUSIONS: Cardiac arrest is an uncommon event among telemetry ward
      patients, and monitor-signaled survivors are extremely rare. Routine telemetry
      offers little cardiac arrest survival benefit to most monitored patients, and a
      more selective policy for telemetry use might safely avoid ECG monitoring for
      many patients.

PMID- 10905644
TI  - Fenoldopam, a dopamine agonist, for hypertensive emergency: a multicenter
      randomized trial. Fenoldopam Study Group.
AB  - Despite successful therapies for chronic hypertension, hospital admissions for
      hypertensive emergency more than tripled between 1983 and 1992. OBJECTIVE: To
      examine the safety and efficacy of fenoldopam, the first antihypertensive with
      selective and specific action on vascular dopamine (DA1) receptors, in a clinical
      trial involving emergency department patients with true hypertensive emergencies.
      METHODS: Patients with a sustained diastolic blood pressure (DBP) of > or =120 mm
      Hg and evidence of target organ compromise were randomized in a double-blinded
      manner to one of four fixed doses of intravenous fenoldopam (0.01, 0.03, 0.1, or
      0.3 microg/kg/min) for 24 hours. The primary endpoint was the magnitude of DBP
      reduction in each of the three higher-dose groups after four hours of fenoldopam
      treatment compared with the lowest-dose group. RESULTS: One hundred seven
      participants from 21 centers were enrolled, and 94 patients received fenoldopam.
      Evidence of acute target-organ damage included new renal dysfunction or hematuria
      (50%), acute congestive heart failure or myocardial ischemia (48%), and
      papilledema or grade III-IV hypertensive retinopathy (34%). The DBP decreased in
      a dose-dependent fashion, with significant differences between the 0.1- and 0.3
      microg/kg/min groups compared with the lowest-dose group. Treatment was well
      tolerated, and there were no deaths or serious adverse events during follow-up,
      up to 48 hours. All patients were successfully transitioned to oral or
      transdermal antihypertensives with maintenance of blood pressure control.
      CONCLUSIONS: Fenoldopam safely and effectively lowers blood pressure in a dose
      dependent manner in patients with hypertensive emergencies. Observations
      supporting potential risk factors for hypertensive emergency are discussed.

PMID- 10905645
TI  - Evaluation of protocols allowing emergency medical technicians to determine need
      for treatment and transport.
AB  - OBJECTIVE: To determine whether emergency medical technicians (EMTs) can safely
      apply protocols to assign transport options and to assess agreement between
      groups of providers on application of the protocols. METHODS: Developed protocols
      categorized patients as: 1) needs ambulance; 2) go to the emergency department
      (ED) by alternative means; 3) contact primary care provider (PCP); or 4) treat
      and release. After education on the application of the protocols, first
      responders and ambulance EMTs categorized patients at the scene prior to
      transport but did not change current practice. Ambulance reports were reviewed
      using a predetermined list of critical events that signified the need for an
      ambulance. RESULTS: The EMTs categorized 1,300 study patients as follows: 1,023
      (79%) needed ambulance transport, 200 (15%) could go to the ED by alternative
      means, 63 (5%) could contact a PCP, 14 (1%) could be treated and released.
      Categorizations by a first responder and the transporting EMT were compared for
      209 patients. Collapsing categories to "need ambulance/do not need ambulance"
      showed fair concordance (kappa = 0.51). Initially, 30 of 277 (11%) patients
      determined not to need an ambulance appeared to experience a critical event.
      After review, 23 patients had events that may not warrant advanced life support
      transport. Seven (3%) had critical events in the ambulance warranting ambulance
      transport. Most were miscategorized by the EMT. Overall sensitivity and
      specificity for identifying patients needing ambulance transport were 94.5% and
      32.8%, respectively. CONCLUSIONS: From 3% to 11% of patients determined on scene
      not to need an ambulance had a critical event. Emergency medical services systems
      need to determine an acceptable rate of undertriage. Further study is needed to
      determine whether better adherence to the protocols might increase safety.

PMID- 10905646
TI  - Emergency medicine residents' shiftwork tolerance and preference.
AB  - OBJECTIVES: To determine the shift lengths currently worked by emergency medicine
      (EM) residents and their shift length preferences, and to determine factors
      associated with EM residents' subjective tolerance of shiftwork. METHODS: A
      survey was sent to EM-2 through EM-4 allopathic EM residents in May 1996. This
      questionnaire assessed the residents' shift length worked, shift length
      preferences, night shift schedules, and self-reported ability to overcome
      drowsiness, sleep flexibility, and morningness-eveningness tendencies. When
      providing shift length preferences, the residents were asked to assume a constant
      total number of hours scheduled per month. RESULTS: Seventy-eight programs
      participated, and 62% of 1,554 eligible residents returned usable surveys.
      Current shift lengths worked were 8 hours (12%), 10 hours (13%), 12 hours (37%),
      combinations of 8-hour, 10-hour, or 12-hour (34%) shifts, and other combinations
      (4%). Seventy-three percent of the respondents indicated that they preferred to
      work 8-hour or 10-hour shifts, and only 21% preferred a 12-hour shift. Shiftwork
      tolerance was recorded as: not well at all (2%), not very well (14%), fairly well
      (70%), and very well (14%). The EM residents' eveningness preference, ability to
      overcome drowsiness, sleep flexibility, younger age, and having no children at
      home were all associated with greater shiftwork tolerance. CONCLUSIONS: Emergency
      medicine residents generally tolerate shiftwork well and prefer 8-hour or 10-hour
      shift lengths compared with 12-hour shift lengths. Emergency medicine residencies
      with 12-hour shifts should consider changing residents' shifts to shorter shifts.

PMID- 10905647
TI  - Unique curriculum for emergency medicine residents as medical directors for rural
      out-of-hospital agencies.
AB  - BACKGROUND: Many rural communities have difficulty maintaining a medical director
      for their emergency medical services (EMS). Local physicians may be overwhelmed,
      be hesitant to take on additional responsibilities, and feel unskilled in
      providing the necessary leadership. Without a medical director, rural EMS
      agencies are frequently forced to shut down, thus depriving the community of
      local out-of-hospital care. OBJECTIVES: To meet the needs of rural EMS agencies
      for medical direction, to provide a unique opportunity for emergency medicine
      (EM) residents to acquire EMS medical direction skills, and to fulfill the
      obligation of EM residencies to provide both didactic and experiential training
      in EMS. PROGRAM DESCRIPTION: This article describes a curriculum, now being used
      in Colorado, for placing EM residents as EMS medical directors for rural out-of
      hospital agencies that have lost their medical directors. Residents visit these
      rural communities 6-12 times a year, provide continuing education through
      interactive lectures, develop or revise EMS protocols and policies, perform
      quality assurance reviews, troubleshoot problems, and assist in EMS planning for
      the community. Residents are supervised by the Colorado state EMS medical
      director. CONCLUSIONS: This unique program enables local EMS agencies to continue
      their service while providing clear educational benefit for the EM residents.
      This paper demonstrates how this program has been working successfully in the
      state of Colorado by placing residents in four distinct rural and mountainous
      communities.

PMID- 10905649
TI  - The costs of inadequate data.

PMID- 10905648
TI  - Sore throat and weakness in an injection drug user.

PMID- 10905650
TI  - Opening a dialogue on ethics.

PMID- 10905651
TI  - Research ethics: ethical issues of data reporting and the quest for authenticity.
AB  - The search for truth and its unbiased reporting are ultimate goals of conducting
      scientific research. Ideally, the reporting of research data ought to be an
      objective task. In practice, however, it is fraught with numerous statistical and
      ethical pitfalls, seldom addressed in formal emergency medicine training. The
      lure of academic celebrity and related influences may persuade researchers to
      report results in ways that make data appear more interesting, or worthy of
      publication. Several examples of potentially misleading data reporting are
      illustrated, including using inappropriate statistical tests, neglecting negative
      results, omitting missing data points, failing to report actual numbers of
      eligible subjects, using inappropriate graph labels or terminology, data
      dredging, and others. Although potentially inaccurate or inflated methods of data
      reporting may not constitute overt scientific misconduct, the intentional
      misrepresentation of data is a form of fraud or deception. Publicly funded
      academic inquiry is a privilege and honor enjoyed by a trusted few. Regardless of
      outcome, every effort should be made to report data in the most scientifically
      accurate method. To this end, the Society for Academic Emergency Medicine Code of
      Conduct and American College of Emergency Physicians Code of Ethics provide
      important guidance toward the accurate, compassionate, competent, impartial, and
      honest conduct of scientific research. Accuracy and authenticity in data
      reporting are first and foremost a matter of individual integrity, and are
      crucial to the preservation of academic credibility, the protection of future
      patients, and the public's trust in the medical research enterprise.

PMID- 10905652
TI  - Patient satisfaction investigations and the emergency department: what does the
      literature say?
AB  - BACKGROUND: Patient satisfaction is an indicator of the quality of care provided
      by emergency department (ED) personnel. It is this perception of satisfaction
      that becomes the basis for future ED choice or the recommendation of a specific
      ED to other potential patients. OBJECTIVE: To perform an evidence-based
      literature review to: 1) characterize measures of "patient satisfaction"; 2)
      identify factors that have been associated with overall ED patient satisfaction;
      3) critique the methods used to assess patient satisfaction in the literature;
      and 4) address how this information can be beneficial to those reading the
      satisfaction literature or designing a satisfaction survey instrument. METHODS:
      The MEDLINE database was searched for studies addressing ED patient satisfaction,
      from January 1976 through July 1999, using MeSH terms and a text word search.
      Bibliographies of manuscripts also were searched for additional relevant articles
      and each clinical study was used as a search criterion in Science Citation Index,
      from the date of publication through July 1999. RESULTS: Multiple measures have
      been used to evaluate overall patient satisfaction. Sixteen studies were found
      associating ED patient satisfaction with service and patient factors. Most
      studies are observational and of these, most are cross-sectional. Hence, cause
      and-effect determination of factors responsible for patient satisfaction cannot
      be resolved using the current literature. CONCLUSIONS: Despite considerable
      methodologic variability, key themes (e.g., association of satisfaction with
      patient information, provider-patient interpersonal factors, and perceived
      waiting time) emerge from review of the ED patient satisfaction literature. To
      standardize future investigations, clinicians and investigators should use a
      common definition for the state of overall patient satisfaction, e.g., when the
      patient's own expectations for treatment and care are met (or exceeded). This
      common definition should be incorporated into the instrument used to measure
      overall ED patient satisfaction.

PMID- 10905653
TI  - Patient education in the emergency department.
AB  - The emergency department (ED) visit provides an opportunity for patient
      education. Many ED patients have poor access to regular health care, including
      patient education. Accreditation standards, legal considerations, and cost
      efficiency concerns encourage the clinician to implement formal patient education
      in the ED. More importantly, published clinical studies evaluating patient
      education in both the ED and comparable settings support the hypothesis that ED
      based patient education improves outcomes. The article discusses considerations
      for instructional material, highlights challenges to ED-based patient education,
      and suggests possibilities for future research.

PMID- 10905654
TI  - Parental knowledge of different acetaminophen concentrations for infants and
      children.

PMID- 10905656
TI  - Negotiation with managed care.

PMID- 10905655
TI  - Identification and description of esophageal intubation using ultrasound.

PMID- 10905658
TI  - Actions taken by the American Medical Association.

PMID- 10905657
TI  - Perimortem cesarean section.

PMID- 10905659
TI  - Maternally inherited hearing impairment.
AB  - Mitochondria are intracellular organelles responsible for the majority of a
      cell's energy production. They have their own small maternally inherited genome
      which, when mutated, can give rise to a large spectrum of diseases. The phenotype
      most commonly includes neurological and muscular symptoms, although hearing
      impairment is an additional feature in some mitochondrial syndromes. Often,
      syndromic mutations affect only a fraction of all mitochondrial DNA molecules, a
      condition referred to as heteroplasmy. It is believed that the degree of
      heteroplasmy in different tissues contributes to the phenotypic heterogeneity
      that is a hallmark of these syndromes. Five homoplasmic mutations leading to
      nonsyndromic hearing impairment have been reported (1555A-->G, 7445A-->G,
      7472insC, 7510T-->C, 7511T-->C). The 1555A-->G is in the 12S rRNA gene, and in
      some populations, appears to be a frequent cause of hearing impairment. Carriers
      of the mutation are abnormally sensitive to aminoglycoside-induced ototoxicity
      even at 'appropriate' drug levels; in addition, even without aminoglycoside
      exposure, these persons can develop hearing impairment. The other four
      nonsyndromic mutations are located in the tRNA(Ser(UCN)) gene. In addition to
      hearing impairment, with two of these mutations (7445A-->G, 7472insC), other
      symptoms can be present in some patients. However, why these five mutations
      preferentially affect the inner ear, despite the crucial role of mitochondria in
      nearly all cells of the body, is unknown.

PMID- 10905660
TI  - Images in genetics. Genetic landmarks through philately--Jean Martin Charcot
      (1825-1893) and Charcot-Marite--tooth disease.

PMID- 10905661
TI  - Sporadic cardiac and skeletal myopathy caused by a de novo desmin mutation.
AB  - Desmin myopathy is a familial or sporadic disorder characterized by
      intracytoplasmic accumulation of desmin in the muscle cells. We and others have
      previously identified desmin gene mutations in patients with familial myopathy,
      but close to 45% of the patients do not report previous family history of the
      disease. The present study was conducted to determine the cause of desmin
      myopathy in a sporadic patient presenting with symmetrical muscle weakness and
      atrophy combined with atrioventricular conduction block requiring a permanent
      pacemaker. A novel heterozygous R406W mutation in the desmin gene was identified
      by sequencing cDNA and genomic DNA. Expression of a construct containing the
      patient's mutant desmin cDNA in SW13 (vim-) cells demonstrated a high pathogenic
      potential of the R406W mutation. This mutation was not found in the patient's
      father, mother or sister by sequencing and restriction analysis. Testing with
      five microsatellite markers and four intragenic single nucleotide polymorphisms
      excluded alternative paternity. Haplotype analysis indicates that the patient's
      father was germ-line mosaic for the desmin mutation. We conclude that de novo
      mutations in the desmin gene may be the cause of sporadic forms of desmin-related
      cardiac and skeletal myopathy.

PMID- 10905662
TI  - MEFV mutations in multiplex families with familial Mediterranean fever: is a
      particular genotype necessary for amyloidosis?
AB  - Familial Mediterranean fever (FMF) is an autosomal recessive disease. It is
      characterized by recurrent febrile episodes in association with peritonitis,
      pleuritis, and arthritis. Progressive systemic amyloidosis is the most important
      complication of FMF that inevitably leads to chronic renal failure. Recently, the
      gene for FMF, MEFV, has been cloned and four missense mutations have been
      described: M694V, M680I, V726A, and M694I. Initial studies have suggested that
      the presence of the M694V mutation carries a significant risk for the development
      of amyloidosis. In this study, we present seven families, in which at least two
      individuals have been diagnosed with FMF and at least one with amyloidosis. Among
      18 individuals, in whom molecular testing was performed for the four
      aforementioned mutations, ten had amyloidosis. None of these ten individuals was
      found to be homozygous for the M694V mutation. In three families, there were two
      sibs with amyloidosis. None of the sib-pairs with amyloidosis was found to have
      the same genotype. There were two or more sibs with the same genotype in four
      families. Only one sib from each family developed amyloidosis in these families.
      These results provide evidence that FMF patients without the M694V mutation are
      also at risk for the development of amyloidosis. Particular mutations themselves
      do not appear to be sufficient to explain the occurrence of amyloidosis in all
      cases with FMF.

PMID- 10905663
TI  - Hypogonadotrophic hypogonadism in Roifman syndrome.
AB  - The combination of spondyloepiphyseal dysplasia, humoral immune deficiency,
      growth retardation, intellectual deficit and characteristic facial dysmorphism
      has recently been delineated as a discrete disorder thus far only reported in
      males. This report describes a fifth individual with co-existent
      hypogonadotrophic hypogonadism, thereby expanding the phenotype and possibly
      offering insight into the genetic aetiology of this condition.

PMID- 10905664
TI  - Mutations of GJB2 in three geographic isolates from northern Tunisia: evidence
      for genetic heterogeneity within isolates.
AB  - Geographically isolated populations have been successfully used to localize genes
      for recessive inherited diseases, including non-syndromic sensorineural recessive
      deafness (NSRD). To date, 25 loci for NSRD have been localized on human
      chromosomes (DFNB loci), and six of the corresponding genes have been identified.
      Here, we report on the contribution of the DFNB1 locus (GJB2 gene) to NRSD in
      seven affected families living in three northern Tunisian geographic isolates,
      and we provide evidence for genetic heterogeneity within isolates. This finding
      challenges the classical view of a single 'founder' mutation segregating in such
      isolates.

PMID- 10905665
TI  - Vertebral anomalies in a new family with ODED syndrome.
AB  - We report a new family with oculodigitoesophagoduodenal syndrome (ODED syndrome),
      which associates microcephaly, abnormalities of the hands and feet, shortened
      palpebral fissures, tracheoesophageal fistula and duodenal atresia. In addition,
      previously unreported vertebral anomalies are described. This report further
      delineates the clinical and radiographic spectrum of this syndrome, providing
      useful information for diagnosis and family counseling.

PMID- 10905666
TI  - Short arm rearrangements of sex chromosomes with haploinsufficiency of the SHOX
      gene are associated with Leri-Weill dyschondrosteosis.
AB  - Twelve patients with different features of Turner syndrome, and with Xp and Yp
      rearrangements involving the pseudoautosomal region (PAR1) are described. In all
      patients, FISH analysis showed loss of one copy of the Short Stature Homeobox
      (SHOX)-containing gene. Ten patients had short stature and one disproportionate
      (mesomelic) normal stature, while the last one had normal stature. Skeletal
      abnormalities, including shortened ulna, were detected in nine subjects, and in
      six of them Madelung deformity was observed. These clinical data indicated a
      genotype phenotype correlation between haploinsufficiency of SHOX, and short
      stature and skeletal abnormalities.

PMID- 10905667
TI  - Hemochromatosis in Galicia (nw Spain): a Celtic influence?

PMID- 10905668
TI  - The comparison of anthropometric variables in mentally retarded boys with and
      without fragile X syndrome.

PMID- 10905670
TI  - Continuous medical education.

PMID- 10905669
TI  - Psychomotor development in Cri du Chat Syndrome.

PMID- 10905671
TI  - Obstructed defaecation: diagnosis and management.

PMID- 10905672
TI  - Management and outcome of traumatic aortic injuries.
AB  - BACKGROUND AND AIMS: Aortic injuries are rare and associated with high early
      mortality challenging the surgical services both from a technical as well as
      organisational point of view, especially in countries with low incidence of
      trauma. A Finnish experience in the management of aortic injuries is reported
      with special emphasis on outcome after early involvement of cardiothoracic
      surgeons. MATERIAL AND METHODS: Retrospective analysis of hospital records
      identified 36 consecutive patients with aortic injuries arriving alive to the
      hospital during a 32-year period of 1967-98. RESULTS: Of the 19 thoracic aortic
      injuries, 17 (89%) were caused by blunt trauma, 8 (42%) of the patients arrived
      in shock, 7 (37%) died before repair could be attempted, 11 (58%) underwent
      repair with prosthesis and one (5%) with sutures, with an overall mortality rate
      of 9/19 (47%). Of the 17 patients with abdominal aortic injuries (15
      penetrating), 13 (76%) arrived in shock, 3 (18%) died before repair, 13 (76%)
      were repaired with sutures and one (6%) with prosthesis, with an overall
      mortality rate of 8/17 (47%). Fourteen (82%) of the 17 non-survivors died within
      24 hours from the injury, 13 from exsanguination and one from associated brain
      injury. CONCLUSIONS: Abdominal aortic injuries are usually penetrating, diagnosed
      intraoperatively and amenable to suture repair with good results indicating that
      stable and unstable patients with potential aortic injuries after penetrating
      abdominal trauma can safely be managed in hospitals with experienced general
      surgeons on call. In contrast, stable patients with suspected thoracic aortic
      injuries could benefit from early transfer to a hospital with cardiothoracic
      surgical facilities and personnel.

PMID- 10905673
TI  - The role of the veno-arteriolar reflex (VAR) in the pathogenesis of peripheral
      oedema in patients with chronic critical limb ischaemia (CLI).
AB  - BACKGROUND AND AIMS: Relatively many patients with chronic critical limb
      ischaemia (CLI) have oedema in the afflicted limb. Previous studies in these
      patients indicate derangement in the Starling forces governing transcapillary
      fluid balance. An impaired veno-arteriolar reflex (VAR) may cause an increase in
      capillary pressure and hence increased filtration pressure resulting in oedema.
      The aim of the present study was to investigate VAR in patients with CLI to come
      to a better understanding of the pathogenesis of ischaemic oedema. MATERIAL AND
      METHODS: Sixteen patients (mean age of 78+/-9.4 years) with unilateral CLI and
      oedema were included. There were two control groups of similar age, one consisted
      of 8 patients with unilateral CLI but without oedema and the other of 9 healthy
      subjects. Laser Doppler fluxmeters were used to evaluate the foot skin
      microcirculation, with the limbs in supine as well as in the dependent position,
      simultaneously in 4 different areas: the pulp of the first toe (Sitel), at the
      level of the second metatarsal body (Site 2), at the anterolateral part of ankle
      (Site 3) and the pulp of the first toe of the contralateral limb (Site 4) as
      reference. Laser Doppler flux (LDF) values (expressed in perfusion unit, PU) were
      recorded with the foot dependent (PUd), in the horizontal position (PUh), and the
      orthostatic response (OR) was calculated at all measuring sites as PUd/PUh.
      RESULTS: In none of the measured sites there was a significant difference in OR
      between the limbs with CLI and oedema and the limbs with CLI but without oedema.
      The median OR of CLI limbs at site 1 [2.5 (0.61-8.96)] was greater than at sites
      2 [0.99 (0.46-2.38), p < 0.01] and 3 [0.95 (0.68-10.31), p < 0.04] respectively,
      while the differences in OR between site 2 and 3 were not significant. The median
      OR in the limbs of healthy controls at sites 1, 2 and 3 were 0.58 (0.37-1.43),
      0.54 (0.28-1.33) and 0.51 (0.34-0.91), respectively. There were no significant
      differences in OR between sites 1, 2 and 3 of the control group. The OR of CLI at
      site 1, 2 and 3 were significantly greater than the corresponding sites in the
      healthy subjects (p < 0.001, p < 0.008, p < 0.001). CONCLUSIONS: The VAR is
      disturbed in limbs with CLI, both in the ones with and without oedema. There were
      regional differences in the OR in these ischaemic feet but there were no
      differences in OR between those with and without oedema. Thus, disturbances in
      VAR may play a role in the development of ischaemic oedema, but is probably not
      the only causative factor.

PMID- 10905674
TI  - Adenovirus-mediated gene transfer into an experimental pancreatic tumour.
AB  - BACKGROUND AND AIMS: Gene therapy has been suggested as a novel approach against
      pancreatic cancer, a disease with a grim prognosis with current modes of therapy.
      Despite recent advances in in vitro and experimental in vivo studies, there is no
      data available concerning gene transfer efficiency in intrapancreatic tumours in
      immunocompetent animal models. MATERIAL AND METHODS: In in vitro studies rat
      pancreatic carcinoma cells (DSL-6A/C1) were transduced with replication-deficient
      adenovirus carrying Escherichia Coli beta-galactosidase (lacZ) gene. Gene
      transfer efficacy was assessed at different multiplicities of infection (MOIs).
      Pancreatic tumours were induced by inoculating cultured DSL-6A/C1 cancer cells
      into Lewis rat pancreases. Established tumours were transduced and three days
      post-transduction, pancreatic tumours as well as other intra-abdominal organs
      were harvested and processed for histological analyses, including staining for
      marker gene expression. RESULTS AND CONCLUSIONS: In vitro assays showed that DSL
      6A/C1 cells were transduced efficiently, even at low MOIs. In vivo gene transfer
      was successful in all animals, and all pancreatic samples showed reporter gene
      expression. Positive cells were detected in the peritumoural areas as well as to
      a lesser extent within the tumours. The transgene activity was not evenly
      distributed and the gene transfer efficiency varied from a few detectable blue
      cells to 11% per field. Our studies demonstrated safe in vivo gene transfer into
      intrapancreatic tumours, suggesting that pancreatic tumours are potential targets
      for in vivo delivery of therapeutic genes.

PMID- 10905675
TI  - Ileal pouch-anal anastomosis operation in children versus adults.
AB  - BACKGROUND AND AIMS: To evaluate early results of elective ileal pouch-anal
      operations in children under the age of fifteen as compared to adult patients
      operated during the same period by the same surgical team. MATERIAL AND METHODS:
      Eighty-two patients with ulcerative colitis underwent restorative proctocolectomy
      during a six-year period, 1991-1996. Twelve of them (16%) were under the age of
      15 years. Peroperative and short term postoperative morbidity were compared
      between the two groups. RESULTS: Covering loop ileostomy was performed on one
      patient in the juvenile group and 5 (7%) in the adult group. There were no
      significant differences in postoperative complications between the two groups.
      Eight (11%) leakages occurred in the adult group as compared to none in the
      juveniles. The children had a higher incidence of unexplained postoperative fever
      (50% versus 21%). Seven adults (10%) but no children underwent re-operation for
      these early complications. CONCLUSIONS: It would appear that a team of
      experienced gastroenterologic surgeons can operate children as well as adults for
      ulcerative colitis with comparable early results without additional morbidity.

PMID- 10905676
TI  - Wound cell variation in closed surgical wounds as measured with two independent
      methods.
AB  - BACKGROUND AND AIMS: It is not known, to what extent the observed cellular
      changes in healing surgical wounds are species-, individual- or site-specific or
      whether they depend on the research method used. The aim of this study was to
      compare two independent methods for harvesting wound cells from porcine wounds
      after two time intervals, and to assess individual changes of wound cell
      composition. MATERIAL AND METHODS: In a standardised wound model in six pigs,
      with eight dorsal skin incision wounds in each, the Cellstick device and the
      Wound Edge Contact (WEC) method were used to collect inflammatory cells from the
      same wounds at hour 6 or 24 post-surgery. The wound cells were stained by the May
      Grunwald-Giemsa (MGG) -method and counted differentially. RESULTS: A significant
      difference was found between the 6 and 24 hour Cellstick specimen in the
      proportions of wound neutrophils (p = 0.007), lymphocytes (p = 0.02) and
      monocytes (p < 0.001). The differential counts of wound cells within each
      individual animal did not significantly differ from each other. Instead, a
      significant difference was found in the wound neutrophils (p = 0.001),
      lymphocytes (p = 0.04) and monocytes (p < 0.001) between the wounds of individual
      animals. The WEC method revealed the same significant differences in the wound
      cell proportions. CONCLUSIONS: The Cellstick and the WEC method gave analogous
      results with equal variances from the incision wounds for up to at least 24 hours
      after injury.

PMID- 10905677
TI  - Risk factors for intraoperative femoral fractures during total hip replacement.
AB  - BACKGROUND AND AIMS: Intraoperative femoral fractures are a serious complication
      of total hip replacement. The purpose of this study was to evaluate the risk
      factors of intraoperative femoral fractures in a retrospective analysis of a
      series of 3,566 total hip replacements. MATERIALS AND METHODS: The patients were
      divided into two groups, A and B. Group A patients had no intraoperative femoral
      fractures and Group B patients had intraoperative femoral fractures. In Group A
      there were 3,483 patients (97.7%) and in Group B, 83 (2.3%). The following
      potential risk factors were evaluated: sex, age, diagnosis, previous surgery at
      the homolateral hip, surgical approach, fixation type of the femoral component,
      prosthesis type, surgical stage during which the fracture occurred, and the lead
      operating surgeon. RESULTS: The fracture incidence was higher in females (p <
      0.005) in uncemented femoral components (p = 0.005), in patients who had previous
      surgery at the homolateral hip (p < 0.005), and in revision surgery (p < 0.005).
      CONCLUSION: The analysis of intraoperative femoral fracture risk factors should
      allow the surgeon to improve the surgical performance and therefore reduce the
      incidence of this severe intraoperative complication.

PMID- 10905678
TI  - The effect of implant design and bone density on maximum torque and holding power
      for femoral neck fracture devices.
AB  - BACKGROUND AND AIMS: Displacement of internally fixed femoral neck fractures due
      to implant migration is a common problem. This in vitro study was performed to
      compare maximum torque and holding power for five different implants. MATERIAL
      AND METHODS: Synthetic porous material with low, medium or high density was used
      to simulate cancellous bone. The tested implants included three conventional
      screws (AO, Olmed, Hansson), one screw with threads and a barb (Hybrid), and a
      pin with a hook (LIH). RESULTS: The Hansson screw provided higher maximum torque
      in low and medium density blocks when compared with the other implants (p <
      0.0001) followed by LIH, Hybrid, Olmed, and AO. For high-density blocks there was
      no significant difference between Hansson and Hybrid screws, both with
      significantly higher torque than the other implants. The maximal pullout in low
      density blocks differed significantly between all five implants with the Hansson
      screw providing the highest holding power. For medium and high-density blocks the
      conventional screws had significantly higher pullout resistance compared with the
      Hybrid and LIH. CONCLUSION: The in vitro model used seemed to provide
      reproducible and clinically relevant results. There was a good correlation
      between material density and holding power for all implants. Screws inserted
      without predrilling provided higher maximal torque while maximal pull out load
      seemed less affected by predrilling being used or not.

PMID- 10905679
TI  - Single-dose antibiotic prophylaxis in osteosynthesis for hip fractures. A
      clinical multicentre study in Finland.
AB  - BACKGROUND AND AIMS: The use of antibiotic prophylaxis in open reduction and
      osteosynthesis of closed hip fractures is still controversial. The aim of this
      study was to demonstrate the effect of antibiotic prophylaxis in osteosynthesis
      of these fractures. MATERIAL AND METHODS: A total of 224 patients operated on
      between November 1994 and February 1998 in six hospitals by internal fixation for
      a fresh hip fracture were prospectively and randomly allocated to either a
      ceftriaxone antibiotic prophylaxis or no prophylaxis group and followed for one
      year. RESULTS: Within 6 weeks after the operation, 2.6% wound infections were
      recorded in the antibiotic group and 4.7% in the control group. Two (1.9%) of the
      five infections in the control group were deep infections (both sensitive to
      ceftriaxone). There were no statistically significant differences between the
      infection rates in both groups. However, when analyzing all complications
      recorded within 6 weeks, significantly more complications were found in the
      control group (p < 0.01). In the multivariate analysis the most important factor
      predicting postoperative complications was the lack of antibiotic prophylaxis.
      CONCLUSION: In this study the antibiotic prophylaxis group had significantly less
      postoperative complications than the control group within 6 weeks after the
      operation.

PMID- 10905680
TI  - Cannulated screws versus hemiarthroplasty for displaced intracapsular femoral
      neck fractures in demented patients.
AB  - BACKGROUNDS AND AIMS: There are no randomised trials comparing internal fixation
      and hemiarthroplasty for a displaced intracapsular femoral neck fracture in
      relation to mental state. MATERIAL AND METHODS: To establish what should be the
      treatment of first choice, a prospective randomised clinical study was performed
      on 60 demented patients with displaced intracapsular femoral neck fractures,
      comparing internal fixation (n = 31) with hemiarthroplasty (n = 29). RESULTS:
      There was no significant difference in the mortality rate of both groups.
      Hemiarthroplasty was associated with significantly more loss of blood and more
      wound complications. Reoperation for secondary displacement of the fracture after
      internal fixation occurred in four patients. Although not-statistically
      significant, failure of internal fixation seemed to be higher after an inadequate
      osteosynthesis. CONCLUSION: Postoperative mortality is high and the chance of
      successful rehabilitation very small for both types of treatment in this group of
      patients. In our opinion, demented patients should not be treated with a major
      surgical procedure like hemiarthroplasty. Internal fixation should be considered
      the treatment of choice, because it is a smaller operation than prosthetic
      replacement, with less morbidity. If adequate reduction can not be achieved, a
      primary hemiarthroplasty should be performed.

PMID- 10905681
TI  - Cast treatment and intramedullary locking nailing for simple and spiral wedge
      tibial shaft fractures--a cost benefit analysis.
AB  - BACKGROUND AND AIMS: The aim of this retrospective study was to compare the
      relative costs of treating simple and spiral wedge (requiring closed reduction
      under anaesthesia) tibial shaft fractures in a plaster cast or with
      intramedullary locking nail. MATERIAL AND METHODS: The material consisted of 26
      fractures treated in a plaster cast and 51 fractures treated with an
      intramedullary locking nail. The costs caused by the direct costs (treatment,
      hospitalisation, and outpatient appointments) as well as indirect costs (lost
      productivity) were taken into account. Costs caused by complications were also
      included in the analysis. RESULTS: Mean direct costs per patient were FIM 22920
      and FIM 26952 and mean overall costs per patient were FIM 120486 and FIM 82224 in
      plaster cast and intramedullary locking nailing groups, respectively (FIM 1 = USD
      0.19). The higher mean overall costs of the plaster cast group were attributable
      to the longer sick leave periods in this group (218 days in plaster cast group
      and 124 in intramedullary nailing group). CONCLUSION: Plaster cast treatment of
      simple and spiral wedge tibial shaft fractures requiring closed reduction under
      anaesthesia is more expensive to society than operative treatment with
      intramedullary locking nail.

PMID- 10905682
TI  - Fatal anaphylactic reaction to protamine after femoropopliteal by-pass surgery.
AB  - BACKGROUND AND AIMS: Administration of protamine might cause serious
      complications especially in patients treated preoperatively with NPH insulin.
      MATERIAL AND METHODS: A case report. RESULTS AND CONCLUSION: Administration of
      protamine sulphate caused fatal anaphylactic reaction to a diabetic patient
      undergoing femoropopliteal by-pass surgery. Care should be taken when
      administering protamine to a patient treated preoperatively with NPH insulin and
      the possibility of an anaphylactid reaction to protamine have to be kept in mind.

PMID- 10905683
TI  - Penetrating cardiac injuries. A complex challenge.

PMID- 10905684
TI  - Adverse events associated with chemotherapy for common cancers.
AB  - Neutropenia is a common and often dose-limiting toxicity associated with
      chemotherapy One way to decrease the severity of this adverse event is to use
      colony-stimulating factors (CSFs) after chemotherapy. Colony-stimulating factors
      are relatively expensive agents, and most institutions limit their use.
      Unfortunately, it is difficult to predict which patients are likely to develop
      neutropenia. An improved ability to predict this situation might help
      institutions and clinicians determine which patients need CSFs as adjunctive
      therapy. The efficacy of CSFs and how they may affect patient outcomes are
      discussed. In addition, a primary literature review on the toxicity associated
      with chemotherapy regimens used for common cancers is summarized. Knowing the
      toxicity of individual regimens may help clinicians identify patients needing
      adjunctive therapy or less toxic regimens. Any action that helps reduce the
      occurrence, or severity, of neutropenia in patients receiving chemotherapy would
      be beneficial and enhance the patient's quality of life.

PMID- 10905685
TI  - A predictive model for neutropenia associated with cancer chemotherapy.
AB  - Studies of primary prophylaxis of febrile neutropenia (FN) with recombinant human
      granulocyte colony-stimulating factor (rHu-G-CSF, filgrastim) administered to all
      patients starting their initial course of chemotherapy have demonstrated clinical
      effectiveness and an economic advantage in a wide range of settings. A recent
      meta-analysis confirmed the ability of filgrastim to reduce the risk of FN and
      documented infection in a variety of malignancies in both adults and children.
      The threshold risk for FN at which a cost saving is achieved by using filgrastim
      is inversely related to the daily cost of the drug and duration of
      hospitalization. Clinical practice guidelines for the use of filgrastim were
      developed based on these observations. Recent studies incorporating indirect
      institutional costs demonstrated that a cost saving can be achieved at
      substantially lower FN risk thresholds than previously estimated. Despite the
      demonstrated efficacy of filgrastim in primary prophylaxis, its value may be
      further increased by appropriately selecting patients and better understanding
      the importance of sustaining dose intensity in specific malignancies. Clinical
      prediction models capable of identifying individuals at high risk for neutropenic
      complications yield further reductions in FN risk thresholds and treatment costs
      in patients receiving cancer chemotherapy. These models also may be used to
      evaluate the cost-effectiveness or cost-efficiency of filgrastim. A clinical
      prediction model recently was presented and validated incorporating both baseline
      clinical characteristics as well as the results of the first cycle of
      chemotherapy in patients with early-stage breast cancer. A cost-effectiveness
      ratio of $34,297/year of life saved was estimated based on dose-response
      assumptions derived from a previously reported adjuvant breast cancer trial
      studying the impact of dose reduction on disease-free survival. The cost
      effectiveness of filgrastim was evident over a wide range of clinical and cost
      assumptions. Clinical prediction models permit the rational and cost-effective
      identification of patients for filgrastim support. Existing clinical practice
      guidelines should be reevaluated in light of new information available on both
      the total costs associated with FN as well as the cost-effectiveness of these
      agents in patients receiving chemotherapy for sensitive and potentially curable
      malignancies.

PMID- 10905686
TI  - Comparison of G-CSF and GM-CSF adverse event profiles in office-based practices:
      preliminary study results.
AB  - We investigated the adverse event profile of colony-stimulating factors (CSFs)
      used in office-based oncology practices in the United States. The impetus for the
      study was anecdotal reports from physicians and nurses working in community
      practice settings describing the differences in adverse drug events (ADEs) that
      their-patients experienced with the two CSFs currently available in the United
      States. The study was a retrospective review of office-based oncology practice
      records. The frequencies of drug-induced fever and other ADEs secondary to
      granulocyte (G)-CSF were compared with those of granulocyte-macrophage (GM)-CSF.
      Adverse drug events were those events that were documented by a clinician as
      being causally linked to CSF therapy and not obviously due to other causes. This
      preliminary report of the data indicated that there were some significant
      differences in the ADEs attributable to either G-CSF or GM-CSF. The appropriate
      use of CSFs in clinical practice also is discussed.

PMID- 10905687
TI  - Economic and humanistic impact of adverse events associated with CSFs.
AB  - The current economic health care environment is causing considerable challenges
      for hospital pharmacy. As pharmacy managers attempt to deal with managing the
      costs associated with pharmaceuticals, there is considerable pressure to account
      for the clinical outcomes associated with drug therapy. Particularly in cancer
      treatment as high-cost biopharmaceuticals have infiltrated the care of these
      patients, pharmacy managers must account for reimbursement issues, clinical
      outcomes, patient satisfaction and demands, budgetary costs, and appropriate use
      of costly resources. Consequently, managers need to develop strategies to address
      these concerns. Ideally, pharmacoeconomics should be used to incorporate the
      costs of clinical outcomes and drug costs into the overall evaluation of drug
      therapy. Unfortunately, for a variety of reasons, the practical application of
      pharmacoeconomics is not universally employed and, as a result, most evaluations
      rely on only drug costs. A method to assess the economic impact of clinical
      outcomes associated with adverse drug events and cancer chemotherapy is
      described.

PMID- 10905689
TI  - Application of chromatography and mass spectrometry to the characterization of
      food proteins and derived peptides.
AB  - The following review describes the development of mass spectrometry off-line and
      on-line coupled with liquid chromatography to the analysis of food proteins. It
      includes the significant results recently obtained in the field of milk, egg and
      cereal proteins. This paper also outlines the research carried out in the area of
      food protein hydrolysates, which are important components in foodstuffs due to
      their functional properties. Liquid chromatography and mass spectrometry have
      been particularly used for the characterization of food peptides and especially
      in dairy products.

PMID- 10905688
TI  - Interactive discussion on chemotherapy-related adverse events.

PMID- 10905690
TI  - Electrophoresis of cereal storage proteins.
AB  - Cereal proteins have been studied by a number of analytical techniques over the
      years. One of the major methodologies utilized by cereal chemists has been
      electrophoresis. Starting with moving boundary electrophoresis and progressing to
      slab gels and high-performance capillary electrophoresis, innovative methods have
      been developed to provide high resolution separations of difficult to separate
      proteins. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE),
      acid-PAGE, isoelectric focusing, free zone CE, and even high-resolution two
      dimensional HPLC-HPCE methods have been developed to separate cereal proteins.
      This review focuses on electrophoretic methods for separating and characterizing
      cereal storage proteins.

PMID- 10905691
TI  - Determination by perfusion reversed-phase high-performance liquid chromatography
      of the soybean protein content of commercial soybean products prepared directly
      from whole soybeans.
AB  - The use of soybean flour as external standard for the determination of soybean
      proteins in soybean products directly prepared from whole soybeans is
      investigated. For that purpose a perfusion reversed-phase high-performance liquid
      chromatography method consisting of a linear binary gradient acetonitrile-water
      (both with 0.1% trifluoroacetic acid) in 3 min at a flow-rate of 3 ml/min, and a
      temperature of 60 degrees C is used. Samples dissolved in water are directly
      injected in the chromatographic system. The method is validated by evaluating
      detection limits, precision, and accuracy and applied to the quantitation of
      soybean proteins in soybean products directly prepared from whole soybeans.

PMID- 10905692
TI  - Characterization of commercial soybean products by conventional and perfusion
      reversed-phase high-performance liquid chromatography and multivariate analysis.
AB  - Conventional and perfusion reversed-phase high-performance liquid chromatography
      are used to characterize commercial soybean products for human consumption. For
      this purpose, previously optimized methods of conventional and perfusion
      chromatography applied to the separation of soybean proteins are employed. Sixty
      different samples corresponding to 26 different trademarks of soybean products
      [soybean protein isolate, soybean flour, textured soybean, soybean milks (liquid
      and powdered), and soybean infant formulas] are analyzed. Characterization of
      soybean products is carried out on the basis of their protein profiles obtained
      by both chromatographic methods. Data obtained are processed using multivariate
      methods such as principal components and discriminant analysis. Perfusion
      chromatography enables a further and faster characterization of commercial
      soybean products than conventional chromatography, of great value in the quality
      control of this kind of product.

PMID- 10905693
TI  - Evaluation of the effect of rennet type on casein proteolysis in an ovine milk
      cheese by means of capillary electrophoresis.
AB  - Capillary electrophoresis was used to study the evolution of casein throughout
      the ripening process of Roncal Denomination of Origin ewe's milk cheese and to
      assess the type of rennet in its hydrolysis. Two manufactures were prepared, each
      with four vats; two of them had added lamb artisan rennet, batch A [clotting
      activity of 97.54 rennet units (RU) ml(-1)] and batch B [clotting activity of
      16.26 RU ml(-1)]; one vat included calf industrial rennet, batch I (clotting
      activity of 45.70 RU ml(-1)); and the fourth vat had added mixed rennet, batch M,
      a 50:50 mixture of lamb (batch A) and calf (batch I) (clotting activity of 77.53
      RU ml(-1)). The content of casein nitrogen in fractions alpha-casein1CE, alpha
      casein2CE, beta-casein1CE and beta-casein2CE was quantified in cheese after 1,
      15, 30, 60, 120 and 180 days of ripening. Beta-casein fractions undergo lesser
      degradation during the ripening time than alpha-casein proteins. The degradation
      of alpha-caseins is very much influenced by the clotting activity of the rennet
      used, so that the more active the clotting activity the greater the hydrolysis of
      those caseins. Nevertheless, it is at the level of beta-caseins that we observe
      the evidence of the influence of the type of rennet, thus noting a less intense
      proteolytic activity in the batch made with calf rennet, batch I.

PMID- 10905694
TI  - Effect of the activity levels of the added proteolytic enzyme mixture on free
      amino acids in ripening Ossau-Iraty cheese.
AB  - A proteolytic enzymatic preparation (using one of three enzyme concentrations
      and, hence, one of three different enzymatic activity levels) was added (before
      clotting) to the milk used to manufacture Ossau-Iraty ewes'-milk cheese. The free
      amino acids were analysed by reversed-phase high-performance liquid
      chromatography and the sulphosalicylic acid-soluble N fraction was quantified by
      the trinitrobenzenesulphonic acid method for use as an index of proteolysis
      during ripening. Sensory analysis of the cheeses began after two months of
      ripening. Use of the enzymatic preparation increased the rate of release of amino
      acids in an amount proportional to the enzyme concentration employed. The effect
      of the preparation was more pronounced in the early months of ripening, with the
      differences in the free amino acid contents of the various batches decreasing as
      ripening progressed. Levels of certain free amino acids, such as taurine,
      tyrosine and valine, were virtually unaffected by the addition of the enzymatic
      preparation, whereas levels of such amino acids as serine, glycine, arginine and
      proline were reduced. Texture defects in the cheeses were observed, namely,
      reduced elasticity and creaminess and increased brittleness. Similarly, enzymatic
      treatment also gave rise to bitter flavours that were not characteristic of the
      normal taste and aftertaste of Ossau-Iraty cheese and these changes were
      proportional to the quantity of enzyme added.

PMID- 10905695
TI  - Chromatographic determination of amino acid enantiomers in beers and raw
      materials used for their manufacture.
AB  - Using gas chromatography (GC) on a chiral stationary phase, accompanied by high
      performance liquid chromatography, beers and raw materials used for manufacturing
      (hops, barley grains, malts) were investigated for the pattern and quantities of
      amino acid enantiomers. Although L-amino acids were most abundant, certain D
      amino acids were detected in all beers and most of the raw materials. Highest
      amounts of D-amino acids were detected in special beers such as Berliner Weisse
      that underwent bottle-conditioning with lactic cultures, and Belgian fruit beers
      produced by spontaneous fermentation. It is demonstrated that GC on chiral
      stationary phases is highly suitable for the quantitative determination of amino
      acid enantiomers in beers and raw materials used for their manufacture.
      Quantities, relative amounts and pattern of amino acid enantiomers can serve in
      particular as chiral markers for the authenticity of special beers.

PMID- 10905696
TI  - Authentication of vegetable oils by chromatographic techniques.
AB  - Food authentication has been evolving continually to situations that were
      basically governed by a global market trend. Analytical techniques have been
      developed or modified to give plausible solutions to the devious adulterations at
      each moment. Classical tests have largely been replaced with newer technical
      procedures, most of which are based on gas chromatography, with some being based
      on high-performance liquid chromatography. Determination of trans-fatty acid and
      sterolic composition, together with sterol-dehydration products, have been used
      most frequently used to detect contamination and adulteration. Sophisticated new
      adulterations, e.g., olive oil with hazelnut oil, represent a new challenge for
      the next millennium, although suggestive proposals for detecting these kinds of
      adulterations are emerging with the contribution of databases and mathematical
      algorithms.

PMID- 10905697
TI  - Chromatographic analysis of unsaponifiable compounds of olive oils and fat
      containing foods.
AB  - The analysis of the "minor components" present in food lipids is usually hampered
      by the large diversity of compounds found in this fraction. High-purity degree
      reagents and solvents, good collection techniques and highly sensitive analysis
      are required in order to accurately identify and quantify these components.
      Chromatographic techniques have proven to be particularly suitable for these
      determinations, especially capillary gas chromatography. This study reports
      several analytical cases of the main classes of components of the unsaponifiable
      matter obtained from olive oils or food matrices.

PMID- 10905698
TI  - Chromatographic analysis of minor constituents in vegetable oils.
AB  - The main group of minor constituents belonging to vegetable oils are reviewed.
      Their importance in the characterization, origin and detection of oil mixtures
      are considered. Also, the determination of these minor components is of great
      value in establishing the oil quality and their genuineness. The most commonly
      used procedures (including the Official methodologies) normally applying
      chromatographic techniques are reviewed. The interference of each component
      within the determination of the other minor constituents are discussed.
      Furthermore, novel procedures for determining those compounds are also presented.

PMID- 10905699
TI  - Analysis of olive and hazelnut oil mixtures by high-performance liquid
      chromatography-atmospheric pressure chemical ionisation mass spectrometry of
      triacylglycerols and gas-liquid chromatography of non-saponifiable compounds
      (tocopherols and sterols).
AB  - We analysed the triacylglycerol, tocopherol and sterol composition of hazelnut
      oil, olive oil and their mixtures (90% olive oil with 10% hazelnut oil, 70% olive
      with 30% hazelnut oil and 50% olive oil with 50% hazelnut oil). The main
      triacylglycerols were 1,2,3-trioleylglycerol, 2,3-dioleyl-1-palmitoylglycerol,
      2,3-dioleyl-1-linoleylglycerol and 2,3-dioleyl-1-stearoylglycerol. Non
      saponfiable compounds (tocopherols and sterols) were derivatised as O
      trimethylsilyl ethers. Alpha-tocopherol was the main vitamin E isomer in all
      samples; however, small amounts of beta-tocopherol and gamma-tocopherol were also
      found. Beta-sitosterol and delta5-avenasterol were the principal sterols in all
      samples; campesterol and stigmasterol were minor sterol compounds in all samples.
      Obtusifoliol, which was a major sterol in olive oil and oil mixtures, was not
      found in hazelnut oil. The discriminant analysis showed that hazelnut oil, olive
      oil and oil mixtures were clearly separated according to their triacylglycerol
      composition.

PMID- 10905700
TI  - Development of phosphine reagents for the high-performance liquid chromatographic
      fluorometric determination of lipid hydroperoxides.
AB  - Phosphine reagents were designed and synthesized as a new type of fluorescent
      reagents for the determination of lipid hydroperoxides in foodstuff and
      biological materials. All phosphine reagents prepared had no fluorescence but
      their oxides, which were produced by the reaction of the phosphines with
      hydroperoxides, had strong fluorescence. Among the phosphine reagents prepared,
      diphenyl-1-pyrenylphosphine had the most suitable properties as a fluorescent
      reagent and was successfully applied to the determination of hydroperoxides by
      batch, flow injection and HPLC post-column methods.

PMID- 10905701
TI  - Determination of vitamins in food-matrix Standard Reference Materials.
AB  - In recent years, the National Institute of Standards and Technology (NIST) has
      developed several food-matrix Standard Reference Materials (SRMs) characterized
      for vitamins and other organic nutrients. NIST uses several "modes" for
      assignment of analyte concentrations in SRMs, one of which includes the use of
      data provided by collaborating laboratories. Certification modes and liquid
      chromatographic methods that were used by NIST for value assignment of vitamin
      concentrations in recently introduced food-matrix SRMs are described in this
      paper. These materials and methods include vitamins D and E in coconut oil (SRM
      1563) by gravimetry and multi-dimensional liquid chromatography (LC); vitamins A,
      E, and several B vitamins by reversed-phase LC and vitamin C by ion-exchange
      chromatography in infant formula (SRM 1846); and carotenoids and vitamins A and E
      by reversed-phase liquid chromatography in a baby food composite (SRM 2383).

PMID- 10905702
TI  - High-performance liquid chromatography of non-polar retinoid isomers.
AB  - Normal-phase high-performance liquid chromatograms of retinal, retinol and
      retinyl palmitate isomers using n-heptane-tert.-butyl methyl ether as mobile
      phase are presented. Methods for the synthesis of various isomers of these
      retinoids are described. This enables one to produce standard chromatograms and
      to select various isomers for cochromatography and the identification of the
      various peaks under study. Assignment of the peaks is based on chromatograms
      published previously in this journal. For the main isomers it is possible to get
      baseline separation of the commonly occurring isomeric forms in a reasonably
      short analysis time.

PMID- 10905703
TI  - Determination of vitamin D2 in emulsified nutritional supplements by solid-phase
      extraction and column-switching high-performance liquid chromatography with UV
      detection.
AB  - This paper deals with a method for solid-phase extraction of trace amounts of
      vitamin D2 (VD2, 19 ng/g) from emulsified nutritional supplements, which contain
      50 kinds of compounds, followed by column-switching high-performance liquid
      chromatography (HPLC) with UV detection at 265 nm. VD2 is present at 1000
      20,000,000 times lower concentration than other components. Bond Elut C18
      cartridge was chosen as for the emulsified nutritional supplements after
      comparison with eight other types. A sample solution was applied to the solid
      phase extraction cartridge and VD2 was eluted by methanol followed by HPLC. The
      effects of sample pH, eluent composition and eluate volume on the retention and
      elution of VD2 on Bond Elut C18 cartridge were examined. The resulting method was
      simple, rapid (analysis time: approximately 20 min), sensitive (detection limit:
      approximately 0.1 ng per injection (200 microl) at a signal-to-noise ratio 3:1),
      and reproducible (relative standard deviation: approximately 6.2%, n=5). The
      calibration graph for VD2 was linear in the range of 0.1-3 ng per injection (200
      microl). Recovery of VD2 was approximately 80% by the standard addition method.

PMID- 10905704
TI  - Chromatographic analysis of tocol-derived lipid antioxidants.
AB  - This paper provides a comprehensive overview of existing chromatographic methods
      for the analysis of tocol-derived lipid antioxidants in various sample matrices.
      After a brief introductory discussion on biological and nutritional aspects of
      the vitamin E active compounds, the review focuses on various techniques for the
      isolation, purification, chromatographic separation, and detection of tocopherols
      and tocotrienols. Compiled published normal-phase (NP) and reversed-phase (RP)
      high-performance liquid chromatographic (HPLC) methods demonstrate general trends
      and analytical variability and versatility of HPLC methodology. The relative
      merits of the two HPLC methods are assessed. NP and RP elution characteristics
      are delineated to aid in the identification of antioxidant components. Technical
      novelty of certain analytical procedures for non-food samples warrants their
      inclusion in this review in light of the potential applicability in food assays.

PMID- 10905705
TI  - Normal-phase high-performance liquid chromatography of tocopherols and
      tocotrienols. Comparison of different chromatographic columns.
AB  - Natural vitamin E is composed of eight different vitamers (alpha-, beta-, gamma-
      and delta-tocopherols and alpha-, beta-, gamma- and delta-tocotrienols). As these
      eight vitamers have different antioxidant and biological activities, it is
      necessary to have quantitative data on each substance separately. The aim of this
      study was to find universal HPLC columns for the separation of all eight
      components and to test if a few columns of the same material (different batches)
      will give reproducible results. Normal-phase HPLC separations of vitamin E
      compounds in a prepared mixture (containing oat extracts, palm oil and tocopherol
      standards) were tried on six silica, three amino and one diol columns. As shown
      by calculations of retention factors (k), separation factors (alpha), numbers of
      theoretical plates (N) and resolutions (Rs), the best separations were obtained
      on three silica columns and two amino columns using 4 or 5% dioxane in hexane as
      the mobile phase as well as on a diol column using 4% tert.-butyl methyl ether in
      hexane as the mobile phase.

PMID- 10905706
TI  - Automated analysis of vitamin E isomers in vegetable oils by continuous membrane
      extraction and liquid chromatography-electrochemical detection.
AB  - A rapid and automated method for the analysis of alpha-, gamma- and delta
      tocopherols in vegetable oils is reported. Continuous extraction of vitamin E
      isomers from oil samples dissolved in Triton X-114 in the presence of methanol
      hexane is achieved and coupled on-line with the chromatographic system. Using an
      acetic acid/sodium acetate buffer in a methanol-water (97:3) solution as the
      mobile phase, a C18 stationary phase and electrochemical detection in the
      coulometric mode, alpha-, gamma- and delta-tocopherol isomers can be successfully
      analyzed within 17 min. Thirteen commercially available oils of olive, sunflower,
      corn and seed mixtures were analyzed using 2,2,5,7,8-pentamethyl-6-chromanol as
      internal standard. The results obtained using three methodologies, one of them
      including classical sample treatment for liposoluble vitamin analysis, were in
      good agreement. To validate the proposed method, analysis of the only BCR
      Reference Material available, with a certified content of alpha-tocopherol
      (margarine CRM 122), was carried out using the automated methodology, the results
      found being in agreement with the certified value.

PMID- 10905707
TI  - Determination of tocopherol acetate in emulsified nutritional supplements by
      solid-phase extraction and high-performance liquid chromatography with
      fluorescence detection.
AB  - The present paper deals with a method of solid-phase extraction of tocopherol
      acetate (TA, 49.6 microg/g) from emulsified nutritional supplements, which
      contains 50 kinds of compounds, followed by high-performance liquid
      chromatography (HPLC) with fluorescence detection The TA concentration is 5 to
      approximately 100,000 times lower than that of other compounds in the samples.
      Measuring the loading capacity of the larger amounts of vegetable oil onto the
      Bond Elut C18 cartridge was examined for the complete retention of smaller level
      of TA. A sample solution was applied to a solid-phase extraction cartridge and
      then TA was eluted by acetonitrile followed by HPLC. This method was suitable for
      the determination of TA in emulsified nutritional supplements. The proposed
      method was simple, rapid (analysis time: ca. 15 min), sensitive [detection limit:
      ca. 0.1 ng per injection (100 microl) at a signal-to-noise ratio of 3:1], and
      reproducible (relative standard deviation: ca. 2.5% (n=5)). The calibration graph
      of TA was linear in the range of 0.1 to 100 ng per injection (100 microl).
      Recovery of TA was over 90% by the standard addition method.

PMID- 10905708
TI  - Rapid determination of vitamin E in vegetable oils by reversed-phase high
      performance liquid chromatography.
AB  - A quick and direct method for measuring tocopherols (alpha, beta+gamma and delta)
      in vegetable oils has been developed using RP-HPLC with UV detection. Previous
      extraction of tocopherols is not required. The oil is diluted in hexane and an
      aliquot is mixed with ethanol containing an internal standard (alpha-tocopherol
      acetate). The chromatographic system consists of an ODS-2 column with a methanol
      water mobile phase. Tocopherols are detected at 292 nm in less than 5 min after
      injection. The method is precise (RSD=2.69%) and has a high mean recovery
      (98.14%).

PMID- 10905709
TI  - Simultaneous determination of alpha-tocopherol and beta-carotene in olive oil by
      reversed-phase high-performance liquid chromatography.
AB  - A reversed-phase high-performance liquid chromatographic method was developed for
      the determination, in one run, of alpha-tocopherol and beta-carotene in virgin
      olive oil. The method involved a rapid saponification and a later extraction with
      a mixture of hexane-ethyl acetate. The chromatographic system consists of an ODS
      2 column with a mobile phase of methanol-water-butanol and a diode-array
      detector. Linearity, precision, recovery and sensitivity were satisfactory. The
      main advantage of the proposed method is the speed and simultaneous determination
      of both compounds at the same time.

PMID- 10905710
TI  - Determination of vitamin K1 in emulsified nutritional supplements by solid-phase
      extraction and high-performance liquid chromatography with postcolumn reduction
      on a platinum catalyst and fluorescence detection.
AB  - Determination of small amounts of vitamin K1 (0.8 microg/g) in nutritional
      supplements with high fat content (20 mg/g) was performed by solid-phase
      extraction and high-performance liquid chromatography (HPLC) with fluorescence
      detection after reduction on a platinum oxide catalyst. The concentration ratio
      of plant oils to vitamin K1 (0.8 microg/g) was about 25,000:1. A sample solution
      was applied to a solid-phase extraction cartridge and vitamin K1 was eluted with
      ethanol, followed by HPLC. The proposed method was simple, rapid (analysis time:
      ca. 12 min), sensitive [detection limit: ca. 0.1 pg per injection (100 microl) at
      a signal-to-noise ratio of 3:1], highly selective and reproducible [relative
      standard deviation: ca. 1.3%. (n=5)]. The calibration graph of vitamin K1 was
      linear in the range of 0-2 pg per injection (100 microl). Recovery of vitamin K1
      was over 90% by the standard addition method.

PMID- 10905711
TI  - Determination of thiamine by high-performance liquid chromatography.
AB  - High-performance liquid chromatographic methods for the determination of thiamine
      (vitamin B1) in foodstuffs or biological tissues and fluids are outlined and
      discussed. The methods are often similar and interchangeable, sample extraction
      and clean up procedures being the major difference. Most of the methods use
      either ultraviolet or fluorescence detection. Fluorescence detection requires
      either precolumn or postcolumn oxidation of thiamine to thiochrome. A number of
      methods are recommended and problems with standardization are emphasized.

PMID- 10905712
TI  - Chromatographic determination of riboflavin and its derivatives in food.
AB  - Three elution methods on two different reversed-phase C18 columns were developed
      to determine flavin derivatives in raw egg white, raw egg yolk, egg powder,
      pasteurised milk, fermented milk products and liver (chicken, calf and pig).
      Additionally, 11 thin-layer chromatography solvent systems were used to confirm
      presence of flavins detected in assessed products. It was found that an Alphabond
      C18 column was not as effective as a Symmetry C18 column. Method A (mobile phase
      gradient of methanol-0.05 M ammonium acetate, pH 6.0 applied on an Alphabond C18
      column) can be used for determination of flavin adenine dinucleotide, flavin
      mononucleotide, riboflavin 4',5'-cyclic phosphate, riboflavin, 10
      formylmethylflavin and 10-hydroxyethylflavin in products that do not contain
      7alpha-hydroxyriboflavin. Method B (mobile phase gradient of methanol
      demineralized water, on an Alphabond C18 column) can be useful to separate flavin
      coenzymes from other flavin compounds or to confirm the presence of 7alpha
      hydroxyriboflavin and 10-hydroxyethylflavin in analysed samples. Method C (mobile
      phase gradient of methanol-0.05 M ammonium acetate, pH 6.0, on a Symmetry C18
      column) allows separation of all flavins detected in tested products: flavin
      adenine dinucleotide, flavin mononucleotide, riboflavin 4',5'-cyclic phosphate,
      riboflavin, 10-formylmethylflavin, 10-hydroxyethylflavin, 7alpha
      hydroxyriboflavin, riboflavin-beta-D-galactoside and riboflavin-alpha-D
      glucoside.

PMID- 10905713
TI  - Dehydroascorbic acid.
AB  - Dehydroascorbic acid (DHA) is an important, interesting but somewhat enigmatic
      compound in biological systems. DHA has many unique properties that set it apart
      from ascorbic acid (AA), and DHA has functions that may be very important beyond
      that in the AA:DHA cycle. Future studies should help to better clarify chemical
      activity of DHA and related products that form from DHA, as well as to highlight
      the role DHA plays in normal cellular homeostasis.

PMID- 10905714
TI  - Enzymatically validated liquid chromatographic method for the determination of
      ascorbic and dehydroascorbic acids in fruit and vegetables.
AB  - A liquid chromatographic method has been described for the determination of total
      vitamin C, ascorbic acid (AA) and dehydroascorbic acid (DHAA) in fruits and
      vegetables. The complete separation of AA and DHAA could be achieved on a C18
      column using 0.2 M KH2PO4 (pH adjusted to 2.4 with H3PO4) as the mobile phase at
      a flow-rate of 0.5 ml/min. Since the detection sensitivity was poor for DHAA even
      at 210 nm, it was estimated as the difference between the total AA after DHAA
      reduction and AA content of the original sample, using dithiothreitol (DTT) as
      the precolumn reductant. The reaction times for the complete conversion of DHAA
      to AA at room temperatures were 150, 120, 90 and 75 min for 1, 2, 4 and 8 mmol
      DTT per mmol of DHAA, respectively. The percentage recovery ranged from 81.7 to
      105.9. AA contents of some selected fruits and vegetables were analyzed
      comparatively by liquid chromatography and enzymatic assay to validate the
      method.

PMID- 10905715
TI  - Use of an amino acid in the mobile phase for the determination of ascorbic acid
      in food by high-performance liquid chromatography with electrochemical detection.
AB  - The possibility of using monosodium L-glutamate (MSG) (20 mM MSG, pH 2.1) in the
      mobile phase for the determination of ascorbic acid (AA) in foods by high
      performance liquid chromatography (HPLC) with electrochemical detection was
      examined. The hydrodynamic voltammogram of AA and the background current were
      also examined. The applied potential was set at 400 mV versus an Ag/AgCl
      reference electrode. It was demonstrated that MSG was a useful mobile phase for
      the determination of AA in foods. This paper also examines the stability of AA
      under various conditions in order to optimize HPLC conditions and the pre-run
      sample stabilization. The proposed method is simple, rapid (analysis time:
      approximately 6 min), sensitive (detection limit: approximately 0.1 ng per
      injection (5 microl) at a signal-to-noise ratio of 3), highly selective and
      reproducible (relative standard deviation: approximately 2.5%, n=7). The
      calibration graph of AA was linear in the range 0.1-50 ng per injection (5
      microl). Recovery of AA was over 90% by the standard addition method.

PMID- 10905716
TI  - Use of nucleic acids in the mobile phase for the determination of ascorbic acid
      in foods by high-performance liquid chromatography with electrochemical
      detection.
AB  - The sodium salts of amino acids, nucleic acids and organic acids were examined in
      a new mobile phase for the determination of ascorbic acid (AA) in foods. It was
      possible to use disodium guanosine-5'-monophosphate (GMP) (20 mM GMP, pH 2.1) in
      a new mobile phase after comparison of five mobile phases. The proposed method is
      simple, rapid (analysis time: ca. 6 min), sensitive (detection limit: ca. 0.1 ng
      per injection (5 microl) at a signal-to-noise ratio of 3), highly selective and
      reproducible [relative standard deviation: ca. 2.7% (n=7)]. The calibration graph
      of AA was linear in the range of 0.1 to 50 ng per injection (5 microl). Recovery
      of AA was over 90% by the standard addition method.

PMID- 10905717
TI  - Analytical techniques for determining biotin.
AB  - Biotin is a vitamin of the B-complex, which plays an important biochemical role
      in every living cell. In the recent years, the interest in this vitamin has been
      rekindled, mainly due to its association with serious human disorders, such as
      the inherited syndrome multiple carboxylase deficiency, which can be successfully
      treated with biotin administration. Diagnosis of biotin deficiency as well as
      monitoring of biotin levels in biological fluids of patients receiving biotin
      treatment is crucial. Equally important is the determination of biotin levels in
      pharmaceutical preparations as well as in food and food supplement products,
      which constitute the main source of biotin in humans. Several analytical methods
      for measuring biotin in various samples, e.g. human fluids, pharmaceutical
      formulations, food material etc., have been reported in the literature. In this
      review, the most representative of these methods are presented, and their
      characteristics are evaluated.

PMID- 10905719
TI  - Determination of organic acids in food samples by capillary zone electrophoresis.
AB  - A comprehensive survey of the use of capillary zone electrophoresis for the
      determination of organic acids in food and beverage samples is presented. The
      analytes discussed in this paper include low-molecular-mass organic acids, amino
      acids, vitamin related compounds and free fatty acids.

PMID- 10905718
TI  - Picomolar quantitation of free sulfite in foods by means of
      [57Co]hydroxocobalamin and radiometric chromatography of [57Co]sulfitocobalamin.
      Method, applications and significance of coexisting sulfides.
AB  - The concentration dependent reaction of sulfite with 57Co-labeled
      hydroxocobalamin (OH57CoCbl) to produce a sulfitocobalamin (SO(3)57CoCbl) adduct
      served as a quantification strategy for foodborne sulfite residues freely
      extracted into pH 5.2, 0.05 M acetate buffer. SO(3)57CoCbl was then resolved
      using SP-Sephadex C-25 gel chromatography and its radiometric detection allowed
      calculation of a standard logit plot from which unknown sulfite concentrations
      could be determined. The sulfite detection range was 6.0 nM-0.3 pM with
      respective relative standard deviations of 4.4-29.4% for 50-microl samples.
      Individual incidences of foodborne sulfite intolerances provoked by L-cysteine or
      sulfite additive use in bakery products, which remained undetected using
      conventional sulfite analytical methods, underscored the quantitative value of
      the method. The analytical significance and occurrences of detectable sulfides
      coexisting with foodborne sulfite residues was also addressed.

PMID- 10905720
TI  - High-performance liquid chromatographic determination of mono-, poly- and
      hydroxycarboxylic acids in foods and beverages as their 2-nitrophenylhydrazides.
AB  - The application of direct derivatization in conjunction with high-performance
      liquid chromatography (HPLC) is described for the determination of both free and
      total carboxylic acids in foods and beverages. The method is based on the
      reaction of the carboxylic acids with 2-nitrophenylhydrazine hydrochloride,
      without complicated isolation steps, which produces their non-volatile hydrazine
      derivatives. The HPLC of a series of carboxylic acid groups was performed
      isocratically with short retention times. The analytical results showed good
      recovery and reproducibility using each internal standard. Due to its excellent
      selectivity and sensitivity, the present method can serve as a useful tool for
      routine determinations of mono-, poly- and hydroxycarboxylic acids in foods and
      beverages.

PMID- 10905721
TI  - Influence of organic solvents in the mobile phase on the determination of
      carboxylic acids and inorganic anions in grape juice by ion chromatography.
AB  - Investigations have been initiated to develop a sufficiently good separation of
      both major and minor organic acids and inorganic anions present in grape musts
      using a Dionex As11 column, a sodium hydroxide gradient elution and a suppressed
      conductivity detection. Separation was complicated in aqueous mobile phase by co
      elutions and selectivity was optimized using organic modifiers that alter ion
      exchange selectivity for hydrophobic ions. In this study, the influence of three
      different solvents (methanol, ethanol and acetonitrile) on the efficiency of
      column was compared. The best separation of all ions in a synthetic solution was
      achieved with an eluent containing 13% (v/v) methanol and 13% (v/v) ethanol in
      water, the run during only 20 min. This method was next applied to grape juices
      with success and has shown sensitivity and reproducibility. Moreover, sample
      preparation was a simple 20-fold dilution with 0.45 microm filtration and direct
      injection without prior sample clean-up.

PMID- 10905722
TI  - Development and validation of a capillary electrophoresis method for direct
      measurement of isocitric, citric, tartaric and malic acids as adulteration
      markers in orange juice.
AB  - Fruit juices each have very distinct organic acids profiles that can be used as
      fingerprints for establishing authenticity. A method has been developed,
      optimised and validated for measuring by capillary electrophoresis citric,
      isocitric, malic and tartaric acids as authenticity markers in orange juices,
      without any sample treatment other than dilution and filtration. Final conditions
      were phosphate buffer 200 mM, pH 7.50, -14 kV as applied potential, and 57 cm
      length neutral capillary. Detection was direct UV at 200 nm. Different kinds and
      marks of orange juice, chosen from the great variety existent in the market, were
      analysed and clear differences could be found between them and just pressed
      orange juice.

PMID- 10905723
TI  - Analysis of anthocyanins in foods by liquid chromatography, liquid chromatography
      mass spectrometry and capillary electrophoresis.
AB  - This article reviews recent developments in the methodology for the measurement
      of anthocyanins that offer several advantages over classical methods of analysis.
      The use of UV-diode array and mass spectrometric (MS) detectors, with improved
      methods of liquid chromatography analysis has facilitated identification of these
      analytes. The use of capillary electrophoresis (CE) analysis of the anthocyanins
      under acid conditions has significantly increased peak resolution and improved
      the detection limits by several orders of magnitude. CE offers the advantage of
      economies of very small sample size, very small solvent consumption, and short
      analysis times along with the future possibility of being combined with MS
      detection.

PMID- 10905724
TI  - Determination of tea catechins.
AB  - An overview of analytical methods for the measurement of biologically important
      tea catechins is presented. Liquid chromatography and capillary electrophoresis
      are the most cited techniques for catechin separation, identification and
      quantitation. Liquid chromatography with ultraviolet detection is frequently
      used; however, mass spectrometry, electrochemical, fluorescence and
      chemiluminescence detection are also utilized in cases where more sensitive or
      selective detection is needed. Two modes of capillary electrophoresis, capillary
      zone electrophoresis and micellar electrokinetic capillary chromatography, have
      been employed for the determination of catechins. Both modes of capillary
      electrophoresis are based on ultraviolet detection. Additional analytical
      techniques, such as gas chromatography, thin-layer chromatography, paper
      chromatography, spectrophotometry, biosensing, chemiluminescence and nuclear
      magnetic resonance spectroscopy have also been utilized for the determination of
      catechins and are reviewed herein.

PMID- 10905725
TI  - Analysis of tea components by high-performance liquid chromatography and high
      performance capillary electrophoresis.
AB  - Tea is one of the most popular beverages in the world. The number of reports on
      the analysis of tea components, especially for catechins, has recently been
      increasing. We review the recent reports on the analysis of tea components using
      the analytical methods of high-performance liquid chromatography and high
      performance capillary electrophoresis.

PMID- 10905726
TI  - Comparative analysis of tea catechins and theaflavins by high-performance liquid
      chromatography and capillary electrophoresis.
AB  - This paper describes the simultaneous determination of catechins and theaflavins
      in green and black teas, using reversed-phase high-performance liquid
      chromatography (HPLC) and capillary electrophoresis (CE). The tea polyphenols
      analyzed included (+)-catechin, catechin gallate, (-)-epicatechin, epicatechin-3
      gallate, epigallocatechin, epigallocatechin-3-gallate, theaflavin, theaflavin-3
      monogallate, theaflavin-3'-monogallate and theaflavin-3,3'-gallate. These
      polyphenols together with six other tea ingredients such as caffeine, adenine,
      theophylline, quercetin, gallic acid and caffeic acid were separated within 27
      min by HPLC and in less than 10 min by CE. The optimal analytical conditions of
      both chromatographic methods were investigated for the convenience and
      reliability for routine analysis. Both HPLC and CE were found to be reliable and
      compatible. The reproducibility of the within-day assay using both methods was
      generally >90%. The day-to-day variation of retention time was <5% for HPLC,
      while the variation of migration time for CE was <2%. The analysis time of CE was
      three-times faster, however it is five-times less sensitive than HPLC, which has
      detection limits of 0.05 microg/ml and 0.5 microg/ml for catechins and
      theaflavins, respectively.

PMID- 10905727
TI  - Spectrophotometric and coulometric detection in the high-performance liquid
      chromatography of flavonoids and optimization of sample treatment for the
      determination of quercetin in orange juice.
AB  - The capabilities of spectrophotometric and electrochemical detection techniques
      were investigated for the high-performance liquid chromatographic determination
      of flavonoids. Liquid chromatographic analyses were performed on eleven compounds
      belonging to three different classes of flavonoids: flavanone glycosides, flavone
      and flavonol aglycones. Separation of all compounds examined was carried out
      under reversed-phase conditions on a C18 narrow-bore column for UV detection,
      whereas for electrochemical detection, a C18 standard-bore column was used. UV
      analyses were carried out at 280 nm for flavanones and at 265 nm for flavones and
      flavonols, whereas controlled-potential coulometric measurements were performed
      using a porous graphite electrode. Analytical performances of the methods were
      compared in terms of linearity, limits of detection (LODs) and precision.
      Linearity over two orders of magnitude and LODs at low-ppm levels (0.06-1 mg/l)
      were demonstrated for all techniques considered. Instrumental precision in terms
      of relative standard deviation was found to be between 0 and 5% for the liquid
      chromatography (LC)-UV system and between 0.6 and 10% for the LC-electrochemical
      detection (ED) system. The methods developed were applied to the analysis of
      flavanones and flavonols in a real sample, such as an extract of orange juice.
      Even though quercetin glycoside is mostly present in orange juice as rutin, other
      different glycosides of this flavonol could be present; on this basis, the
      hydrolysis of all glycosides to aglycone allows one to obtain more accurate data
      on the flavonol concentration in orange juice. To avoid sample degradation and to
      increase extraction efficiency, quercetin hydrolysis was optimized using a
      central composite design to investigate the effects of acid concentration and
      hydrolysis time on extraction recovery.

PMID- 10905728
TI  - Analysis of several phenolic compounds with potential antioxidant properties in
      grape extracts and wines by high-performance liquid chromatography-photodiode
      array detection without sample preparation.
AB  - A RP-HPLC method that allows the separation of several types of phenolic
      compounds present in grapes and wines by direct injection of samples, using a
      binary gradient with solvents free of salts and photodiode array detection is
      described. Results show that more than 15 different phenolic molecules with
      antioxidant properties (flavan-3-ols, anthocyanins, cinnamic acid derivatives,
      flavonol derivatives and trans-resveratrol) may be separated in a single run by
      direct injection of red wine. The method is also valuable for the analysis of
      these compounds in white wine and in skins, seeds and pulp extracts of red and
      white grapes.

PMID- 10905730
TI  - Analysis of the bioactive alkaloids tetrahydro-beta-carboline and beta-carboline
      in food.
AB  - Simple tetrahydro-beta-carbolines (THbetaCs) and beta-carbolines (betaCs) are
      naturally occurring alkaloids in foods and food processing. This paper reviews
      the methods employed for their analysis. Procedures for THbetaC and betaC
      isolation and clean-up to remove interfering compounds are carried out by liquid
      liquid extraction, and/or better solid-phase extraction under both reversed-phase
      (C18) and cation-exchange mechanisms. Chemical derivatizations of THbetaCs with
      methyl chloroformate, or anhydrides are accomplished before GC-MS. Quantitative
      analysis of THbetaCs and betaCs is made by RP-HPLC (C18) with fluorescence
      detection providing good selectivity and sensitivity. For the same reasons, HPLC
      MS is increasingly applied to these compounds. Electrospray and atmospheric
      pressure chemical ionization easily produce protonated molecules (M+H)+ of both
      THbetaCs and betaCs. Fragmentation by collision induced dissociation or tandem
      mass spectrometry helps to complete trace identification. The occurrence of
      biologically relevant THbetaCs and betaCs in foods highlights the interest of
      accomplishing their analysis. Foods containing those compounds represent a source
      of possible THbetaCs and betaCs in humans.

PMID- 10905729
TI  - Analysis of resveratrol in wine by capillary electrophoresis.
AB  - Capillary electrophoresis (CE) is a new analytical technique that has recently
      been reported as a method for analysis of resveratrol in wine. Several different
      separation approaches have been taken in these reports. In comparison with high
      performance liquid chromatography (HPLC), CE methods have similar sensitivity and
      can discriminate between trans- and cis-isomers of resveratrol. CE methods also
      show promise for analysis of other flavonoid antioxidants (glycosides and
      aglycones) in wine.

PMID- 10905731
TI  - Tetrahydro-beta-carboline-3-carboxylic acids and contaminants of L-tryptophan.
AB  - Methods for the separation, identification, and quantitative assay of
      contaminants of L-tryptophan implicated in eosinophilia-myalgia syndrome (EMS)
      are described. Propylsulfonic acid (PRS), benzenesulfonic acid (SCX), and octyl
      derivatized silica (C8) bonded-phase cartridges were used for the separation; LC
      MS and GC-MS for identification; and HPLC-UV-fluorescence detection for
      quantitative analyses of norharman, harman, tetrahydro-beta-carboline-3
      carboxylic acid (TCCA), 1-methyltetrahydro-beta-carboline-3-carboxylic acid
      (MTCA), 1,1'-ethylidenbis(tryptophan) (EBT), and 3-(phenylamino)alanine (PAA).
      The tissue distribution, excretion, and metabolism of these contaminants of L
      tryptophan associated with EMS after acute and chronic dosage regimens are
      described. Considerable amounts of EBT were observed in the large intestine of
      rats administered EBT, showing a transfer without decomposition in gastric fluid.
      In addition, MTCA was detected in the blood and urine as well as the organs of
      rats treated with EBT, suggesting MTCA as a major metabolite of EBT. PAA
      accumulated markedly in the brain, among the organs of rats, after both acute and
      chronic administration of PAA, while MTCA accumulated in the kidneys of rats
      after chronic dosage of MTCA. Ethanol and/or acetaldehyde-induced formation of
      MTCA, as well as tryptophan-induced formation of TCCA, occurred endogenously in
      man and animals.

PMID- 10905732
TI  - Liquid chromatographic determination of biogenic amines in fermented foods after
      derivatization with 3,5-dinitrobenzoyl chloride.
AB  - The reagent 3,5-dinitrobenzoyl chloride (DNBZ-Cl) was tested for pre-column
      derivatization of biogenic amines (BAs). Samples were derivatized within 3 min in
      1 M NaOH at ambient temperature by adding 2-propanole and 50 mM DNBZ-Cl in
      acetonitrile. The reaction was terminated by addition of 2 M HCl. For high
      performance liquid chromatography an encapsulated stationary reversed-phase and
      gradient elution using a ternary gradient system were used. The DNBZ derivatives
      were quantified by their UV-absorption at 260 nm. The structures of the
      derivatives were elucidated using coupling of HPLC with electrospray ionization
      mass spectrometry. Detection limits of BAs were approximately 124-864 microg l(
      1) (injected amounts 203-1410 pg) at a signal-to-noise ratio of 3:1. The
      coefficients of determination were 0.989-0.996, with the exceptions of cadaverine
      (0.976) and serotonin (0.965). The method was applied to the quantitative
      determination of agmatine, cadaverine, histamine, octopamine, 2-phenylethylamine,
      putrescine, serotonin, spermidine, spermine, tryptamine and tyramine, in
      fermented cabbage juices, soy sauces, Misos (soy pastes), fermented fish sauces,
      and anchovy paste.

PMID- 10905733
TI  - Changes in free and conjugated polyamines during starvation of sugarcane juices
      as analyzed by high-performance liquid chromatography.
AB  - Changes of the polyamines (PAs) titer in high- and mid-molecular-mass
      carbohydrates (HMMCs and MMMCs, respectively) obtained from sugarcane juices
      stored for 72 h at pH 5.2 or clarified at pH 8.0 have been studied. Cadaverine
      (CAD) is the most abundant free (S) PA in the MMMC fraction from juices at pH
      5.2, whereas putrescine (PUT) was revealed as the main PA at pH 8.0. A slight
      increase in the free PUT titer can be noted at pH 5.2 for 72 h of juice
      starvation. PAs from MMMC were mainly conjugated to acid-insoluble (PH)
      molecules. Accumulation of PH-PAs with the time of starvation was especially
      significant for PUT and CAD. However, CAD has also been detected in the acid
      soluble (SH) fraction and its concentration increases with the time of starvation
      at pH 5.2. The accumulation pattern of free and conjugated PAs from HMMCs is
      similar to that found for MMMCs although some differences can be observed. For
      instance, the increase in free PUT with the time at pH 8.0 was 2.7-times higher
      in the HMMC fraction than in the MMMC fraction. Conjugated PAs associated to acid
      soluble macromolecules (SH fraction) achieved a level in HMMC fractions higher
      than that observed in the MMMC fraction. Moreover, the reported increase with
      time that was observed in PH-CAD from the MMMC fraction was not observed in the
      HMMC fraction, and, finally, the increase in PH-PUT with the time was lower for
      the HMMC fraction than for the MMMC fraction.

PMID- 10905734
TI  - Chromatographic determination of carotenoids in foods.
AB  - In recent years, there has been particular emphasis on obtaining more accurate
      data on the types and concentrations of carotenoids in foods for various health
      and nutrition activities. The analysis of carotenoids is complicated because of
      the diversity and the presence of cis-trans isomeric forms of this group of
      compounds. In addition, a wide variety of food products of vegetal and animal
      origin, vegetables and animal samples contain carotenoids, and a great range of
      carotenoids can be found in these samples. The characteristic conjugated double
      bond system of carotenoids produces the main problem associated with work and
      manipulation on carotenoids, that is their particular instability, especially
      towards light, heat, oxygen and acids. For this reason, several precautions are
      necessary when handling carotenoids. Another problem associated with analysis of
      carotenoids is the difficulty in obtaining standard compounds. High-performance
      liquid chromatographic methods for the determination of carotenoids in foods are
      reviewed. The sample extraction and treatment, carotenoid purification and
      standard manipulation are briefly commented on. We present a critical assessment
      of chromatographic methods developed for the determination of carotenoids in
      foods. Finally, some methods for carotenoid ester separation are reviewed.

PMID- 10905735
TI  - Monoterpenes in grape juice and wines.
AB  - The importance of monoterpenes on varietal flavour of wines has been reviewed.
      These compounds were mainly found linked to sugar moieties in the grape juice and
      wines, showing no olfactive characteristics. In this way, mechanisms to liberate
      terpenes were studied, making a comparative study between acidic and enzymic
      hydrolysis of terpene glycosides. Finally, analytical techniques developed to
      study these compounds, in both free or glycosidically forms, and also to
      fractionate glycosidic precursors, have been discussed.

PMID- 10905736
TI  - Analysis of organic sulfur compounds in wine aroma.
AB  - Sulfur-containing compounds in wines have been extensively studied because of
      their effect on wine aroma. The aim of this paper was to give an overview on the
      analytical methods developed to determine them in wines with special emphasis on
      gas chromatographic methods, as well as the results obtained. In addition, the
      problems occurring in application of the common extraction procedures, such as
      liquid-liquid extraction, static and dynamic headspace and solid-phase
      microextraction, are presented and discussed.

PMID- 10905737
TI  - Analysis of low-volatility organic sulphur compounds in wines by solid-phase
      microextraction and gas chromatography.
AB  - A method for analysing low-volatility sulphur compounds using solid-phase
      microextraction has been developed. The analytes were extracted directly from the
      liquid sample using fibres coated with different stationary phases. The best
      extraction efficiency was obtained with Carboxen-polydimethylsiloxane coating.
      Ionic strength, sample volume, time and temperature of the extraction were
      optimised and the matrix effect studied. The method enables 15 sulphur compounds
      in wine to be determined at trace levels with recoveries close to 100% and limits
      of detection between 0.05 and 5 microg/L. The overall method was successfully
      applied to the determination of the sulphur compounds studied in several red,
      white and rose wines.

PMID- 10905738
TI  - Determination of inulin in meat products by high-performance liquid
      chromatography with refractive index detection.
AB  - Inulin is a naturally occurring carbohydrate with beneficial nutritional and
      technological properties. A high-performance liquid chromatographic (HPLC) method
      was developed for the quantitative determination of these beta-fructans in meat
      products, containing this type of additive. The method includes extraction of
      inulin with hot water, followed by hydrolysis with inulinase enzyme, and
      determination of the released fructose by HPLC with refractive index detection.
      An internal standard of rhamnose was used to quantify fructose. The method
      incorporates a sample blank (without inulinase hydrolysis) for each specimen to
      subtract contributions of free fructose and fructose from sucrose. The results
      showed good precision with average RSDs of 2.4% for repeatability and 5.2% for
      reproducibility. Analytical recovery ranged from 102 to 106%. Satisfactory
      linearity (r=0.999) was obtained.

PMID- 10905739
TI  - High-performance liquid chromatographic determination of Maillard compounds in
      store-brand and name-brand ultra-high-temperature-treated cows' milk.
AB  - Furosine and furfural products of the Maillard reaction are used as specific
      indicators of the effect of heating treatments on milk quality. Their contents
      were measured in representative samples of store- and name-brand ultra-high
      temperature-treated milks using RP-HPLC with UV detection. Furosine contents
      ranged from 40.32 to 50.67 and from 65.48 to 310.58 mg/100 g protein in name- and
      store-brand milks, respectively. Of the furfurals, only hydroxymethylfurfural was
      detected. The free hydroxymethylfurfural contents of store-brand milks ranged
      from 0.22 to 1.70 mg/100 g protein. Total hydroxymethylfurfural contents ranged
      from 0.29 to 0.41 and from 0.72 to 2.21 mg/100 g protein, for name- and store
      brands, respectively.

PMID- 10905740
TI  - Advances in the determination of inorganic anions by ion chromatography.
AB  - The time period covered for this review includes articles published from 1997 to
      1999, with the addition of a few classic references. The purpose of the review is
      to include the most relevant works from each topic area of the determination of
      inorganic anions by ion chromatography, including new sample pretreatments, new
      separation methods, new detection systems and the latest applications in the
      field of environmental, water, foods, etc. samples. Experimental conditions such
      as stationary phase, eluent, detection mode, as well as matrix are summarized in
      a table.

PMID- 10905741
TI  - Determination of oxalate, sulfate and nitrate in honey and honeydew by ion
      chromatography.
AB  - An ion chromatographic method for determining the anions oxalate, sulfate and
      nitrate in honey and honeydew samples is described. To prevent matrix
      interference and to isolate the anions a clean-up step using solid-phase
      extraction on anionic cartridges and eluting with a 0.01 M chromate solution is
      recommended. The anions are separated on an anionic column with a mobile phase of
      borate-gluconate buffer and using conductimetric detection. The method is applied
      to the analysis of samples from different botanical origin.

PMID- 10905742
TI  - Analysis of condensed phosphates in food products by ion chromatography with an
      on-line hydroxide eluent generator.
AB  - An ion chromatographic method with gradient elution using an automated eluent
      generator was developed for the simultaneous determination of condensed
      phosphates (CPs) such as orthophosphate (P1), pyrophosphate (P2), polyphosphate,
      trimetaphosphate and phytate in food products. The linear calibration curves for
      P1, P2, tripolyphosphate, and tetrapolyphosphate in the range 0.5-500 microM had
      a correlation factor of 0.999 or better. The precision of the method for the CP
      peak areas obtained with the hydroxide eluent generator was better than that
      obtained with potassium hydroxide eluents prepared off-line. This method was
      applied to the determination of CPs in food products such as ham, fish paste, and
      cheese extracted by trichloroacetic acid.

PMID- 10905743
TI  - Determination of lithium in wines by ion chromatography.
AB  - Lithium ion can be added as a denaturing agent to wines unsuitable for
      consumption. Accuracy of flame atomic emission spectroscopy with direct
      nebulization, which is commonly adopted for discovering illegal use of denatured
      wines, was found to be compromised by Na+, K+, NH4+, Mg2+, Ca2+ and ethanol
      contained in wine. Ion chromatography (IC) was tested in order to propose an
      alternative method for legal controls. Experimental design was used to
      investigate the influence on the accuracy of the determination of Li+ at ppb
      levels, of Na+ and ethanol content of wine and of fluctuations of eluent flow
      rate and composition. It turned out that IC quantification of Li+ can be affected
      by eluent parameters rather than by wine composition. Since the former can be
      maintained under the operators control, while the latter cannot, IC was judged
      preferable to AES for legal controls of Li+ in wines.

PMID- 10905744
TI  - The industry view on long-term toxicology testing in drug development of human
      pharmaceuticals.
AB  - The approach to chronic toxicity testing over the past decade is reviewed and
      assessed in the light of developing ICH guidelines. The 1990's have seen a
      general acceptance that studies with a maximal duration of 6 months in rodents
      are all that is required for adequate safety assessment of developmental
      pharmaceutical agents. However, controversy has arisen concerning the most
      appropriate duration for chronic toxicity testing in non-rodents. Initial
      suggestions that 6 months duration was sufficient have been countered by findings
      noted in 12-month studies that were not seen in shorter-term studies.
      Retrospective analysis of available data eventually lead to a subsequent ICH
      recommendation that studies of 9 months duration would be now acceptable.
      However, until recently the FDA position on this recommendation was unclear and
      an analysis of industry practices since the ICH recommendation was made in 1997
      has shown that the 9-month guideline is not widely applied. Recent clarification
      by the FDA will probably result in a continued but limited use of this
      alternative. An industry view on the future of chronic toxicology testing in
      rodents and non-rodents is presented.

PMID- 10905745
TI  - Preclinical safety assessment: in vitro -- in vivo testing.
AB  - In vitro--and in vivo preclinical safety tests on drug candidates needed before
      first dose in man and before marketing authorisation are as follows: The acute
      and repeated dose toxicity studies, the reproductive toxicity studies, the
      genotoxicity studies, the carcinogenicity studies and finally the safety
      pharmacology studies. The Safety Assessment of the results with respect to
      predictability for humans is discussed, as well as new tests under validation.
      Suggestions for changes in the future of Non-Clinical Safety tests are mentioned.

PMID- 10905746
TI  - First exposure in man: toxicological considerations.
AB  - The safety of a volunteer/patient who participate in the very first human trial
      relies on data from animal experimentation and on the design of the trial.
      Recommendations on the type and extent of preclinical safety studies that should
      be conducted prior to first dose in man have been developed by the International
      Conference on Harmonisation, and the European Committee for Proprietary Medicinal
      Products. These recommendations include studies designed to characterise local
      tolerance and general toxicity of the drug candidate as well as its genotoxic
      potential and ability to interfere with reproduction. For trials which can be
      categorised as low dose PK screening trials and trials with products where rodent
      and non-rodent (primarily dog) models do not show any biological response (e.g.
      some biotechnology-derived hormones and cytokines) other testing paradigms should
      be used. The present recommendations for preclinical testing have had an
      important impact on the documented impressive safety record of phase I clinical
      trials. In this spirit we extend our warmest and sincerest thanks to Professor
      Jens S. Schou for his long and deep engagement in European and International
      harmonisation of preclinical test recommendations. His efforts have had a
      substantial impact on the present testing recommendations, which are of obvious
      benefit to the safety of the patient.

PMID- 10905747
TI  - Pharmacovigilance based on prescription databases.
AB  - Prescription databases are indispensible in drug safety research and
      surveillance. For suspected rare serious adverse drug reactions, the confirmation
      and quantitative risk assessment requires proper epidemiological studies. Often
      prescription databases provide the information on drug exposure for such studies.
      Aberrant drug utilization in terms of overuse, underuse, polypharmacy etc. may be
      a threat to the health of the patient, and these aspects can best be studied by
      prescription databases. In cases of international drug safety alerts,
      prescription databases may provide information required for rational actions to
      be taken.

PMID- 10905748
TI  - Spontaneous ADR reporting and drug safety signal induction in perspective. To
      honour Professor Jens Schou.
AB  - Drug safety signals will continue to come mainly from the reporting of alert
      clinicians and every effort should be made to enhance this and to ease the
      process. The use of multipurpose health databases for finding signals has much
      potential, if they are better planned so that the appropriate data is captured
      and examined routinely. Consumer reports give us information about their concerns
      and should not be ignored. Better information is needed on poisoning, drug misuse
      and on herbal remedies. The analysis of signals must be improved and speeded up,
      if we are even to maintain our current safety standards, given the global release
      of 'blockbuster products'. Benefit-risk analysis of medicines needs to be better
      understood in relationship to actual clinical use, both from an individual and
      public health perspective. Such analysis should become more logical rather than
      just listing the benefits and risks, and then expressing an essentially
      unsupported opinion. This is essential if therapies are to be compared, and their
      costs justified. The communication of medicines safety and benefit-risk
      information to clinicians, other health professionals and patients is an area
      where there needs to be considerable improvements. We need to be better informed
      about the consequences of guidance and warnings given, so that we may improve the
      service we offer to recipients. In the future, information technology, which
      provides exciting possibilities with what it offers now, will help us with all
      the above challenges.

PMID- 10905749
TI  - International pharmacovigilance: developing cooperation to meet the challenges of
      the 21st century.
AB  - Much has been accomplished internationally in the past decade to harmonise the
      much of the process of post-marketing drug risk detection. However, formidable
      challenges exist in harmonising analytical approaches to such data and in
      leveraging international database resources to improve the quality of such data.
      In addition, international challenges continue in the arena of drug risk
      management once a specific risk has been detected. Especially problematic are the
      questions of appropriate methodology and metrics to assess the public health
      impact of our risk management techniques. Finally, international challenges
      remain in the world of drug risk communication to practitioners, dispensers, and
      patients. The primary challenge confronting us is that of providing easily
      accessible, understandable, unbiased information on drug risk to these
      communities so that truly informed decisions about medicines can be made at the
      individual patient level. Only by meeting internationally these challenges in
      drug risk detection, management, and communication can our citizens know how to
      best use these wonderful pharmacological gifts to which we now have access.

PMID- 10905750
TI  - New safe medicines faster: A proposal for a key action within the European
      union's 6th framework programme.
AB  - The global competitiveness of the European pharmaceutical industry is under
      threat. Technology currently available for the development of new medicines is
      unable to match the pace of drug discovery and design; and the ever-growing
      demand for safety, efficacy and quality documentation has increased the cost and
      time involved in getting new medicines on the market. Although the pharmaceutical
      industry is one of the strongest in Europe in terms of research, innovation,
      exports and employment, there are severe restrictions on its ability to create
      wealth and launch safe drugs for the treatment of common and rare afflictions.
      The present situation should not be allowed to continue. For this reason, the
      European Federation for Pharmaceutical Sciences (EUFEPS) has proposed a key
      action under the title "New safe medicines faster" for the forthcoming EU 6th RTD
      framework programme. The key action has three main objectives: to seek new
      technologies capable of more effective selection of potential drug candidates for
      innovative medicines while accommodating safety demands; to use such technologies
      to speed up the pharmaceutical development process and eliminate bottlenecks
      created by initial exploratory drug research; and to cultivate a pan-European
      interdisciplinary network that bridges the gap between industry, academia and
      regulatory authorities. By involving regulatory authorities early on and fuelling
      research and innovation with EU money it should be possible to create a new set
      of recognised European standards whereby new safe medicines can be brought onto
      the market faster and cheaper.

PMID- 10905751
TI  - Safety of biotechnological products.
AB  - The safety of biotechnological products used for medicinal products is addressed
      by EU council directives. The general principles and the regulatory framework for
      the handling of new drug applications within this areas are described both with
      respect to benefit/risk evaluation, quality assessment, preclinical safety and
      efficacy testing.

PMID- 10905752
TI  - Drug safety in relation to efficacy: the view of a clinical pharmacologist.
AB  - The number of registered drugs, and drug expenditure are increasing rapidly in
      Europe, and within the European Union (EU) there are no longer any regulations
      requiring that new drugs have to be better than old ones. At the same time,
      pharmacoepidemiological studies in Europe and USA show that adverse drug
      reactions now may account for up to 10% of the admissions of patients to internal
      medicine wards at a cost of hundreds of millions of US dollars annually. This
      represents a considerable increase compared to 20 years ago. A partial
      explanation is the many shortcomings of many clinical trials and their relevance
      for health care. Adverse drug reactions are often poorly studied and documented
      in these studies and very seldom included in health economical analyses of the
      value of new drugs. Pharmacovigilance is product- rather than utilization
      oriented and quite invisible in clinical medicine. This is regrettable, since up
      to 50% of adverse drug reactions (ADRs) are dose-dependent and thus preventable.
      Hopefully, the rapid progress in molecular and clinical pharmacogenetics will
      provide new tools for clinicians to choose and dose drugs according to the
      individual needs of patients.

PMID- 10905753
TI  - Laboratory diagnosis of patients with acute chest pain.
AB  - The enzyme activities of creatine kinase (CK), its isoenzyme MB (CK-MB) and of
      lactate dehydrogenase isoenzyme 1 (LD-1) have been used for years in diagnosing
      patients with chest pain in order to differentiate patients with acute myocardial
      infarction (AMI) from non-AMI patients. These methods are easy to perform as
      automated analyses, but they are not specific for cardiac muscle damage. During
      the early 90's the situation changed. First creatine kinase MB mass (CK-MB mass)
      replaced the measurement of CK-MB activity. Subsequently cardiac-specific
      proteins troponin T (cTnT) and troponin I (cTnI) appeared on the scene,
      displacing LD-1 analysis. However, troponin concentrations in blood increase only
      from four to six hours after onset of chest pain. Therefore a rapid marker such
      as myoglobin, fatty acid binding protein or glycogen phosphorylase BB could be
      used in early diagnosis of AMI. On the other hand, CK-MB isoforms alone may also
      be useful in rapid diagnosis of cardiac muscle damage. Myoglobin, CK-MB mass,
      cTnT and cTnI are nowadays widely used in diagnosing patients with acute chest
      pain. Myoglobin is not cardiac-specific and therefore requires supplementation
      with some other analyses such as troponins to support the myoglobin value.
      Troponins are very highly cardiac-specific. Only the sera of some patients with
      severe renal failure, which requires hemodialysis, have elevated cTnT and/or cTnI
      without there being any evidence of cardiac damage. On the other hand, the latest
      studies have shown that elevated troponin levels in sera of hemodialysis patients
      point to an increased risk of future cardiac events in a similar manner to the
      elevated troponin values in sera of patients with unstable angina pectoris. In
      addition, the bedside tests for cTnT and cTnI alone or together with myoglobin
      and CK-MB mass can be used instead of quantitative analyses in the diagnosis of
      patients with chest pain. These rapid tests are easy to perform and they do not
      require expensive instrumentation. For routine clinical laboratory practice we
      suggest that in diagnosis of patients with chest pain, myoglobin and CK-MB mass
      measurements should be performed whenever they are requested (24 h/day) and cTnT
      or cTnI on admission to the hospital and then 4-6 and 12 hours later.

PMID- 10905754
TI  - Methods for the determination of plasma total homocysteine: a review.
AB  - Total homocysteine is the sum of all homocysteine species present in plasma. This
      parameter is valuable for the diagnosis and follow up of cobalamine or folate
      deficiencies, and it has been accepted as an independent risk factor for
      premature cardiovascular disease. These reasons justify the introduction of total
      homocysteine assays in the routine clinical laboratory. In the present review, we
      discuss the procedures for sample collection, processing and storage, and review
      the methodologies for measuring total homocysteine. We compare their feasibility
      as routine methods in the clinical laboratory.

PMID- 10905755
TI  - Serum protein 90K/Mac-2BP is an independent predictor of disease severity during
      hepatitis C virus infection.
AB  - The serum protein designated 90K/Mac-2BP has been found at elevated
      concentrations in the sera of patients with various types of cancer and viral
      infections. The importance of the 90K/Mac-2BP serum concentrations in predicting
      the response towards interferon-alpha treatment for hepatitis C virus (HCV)
      infection prompted us to utilize a new ELISA for soluble human 90K/Mac-2BP to
      monitor the serum concentrations of this protein in our HCV-positive patients.
      Seventy HCV-PCR and anti-HCV antibody positive patients were analyzed for their
      serum levels of aspartate aminotransferase, alanine aminotransferase, gamma
      glutamyltransferase, cholinesterase, HCV-viral load, viral subtypes, and 90K/Mac
      2BP. On correlation of age and 90K/Mac-2BP levels, we found an apparent
      correlation that was proved rather to be a strong dependence of 90K/Mac-2BP
      concentrations on disease severity/duration, which increases with age. Multiple
      correlation analysis demonstrated the independent nature of 90K/Mac-2BP
      concentrations, underscoring the potential high utility of this new marker. Our
      data corroborate the potential of the scavenger receptor family protein 90K/Mac
      2BP as an independent predictor of disease severity during HCV infection.

PMID- 10905756
TI  - Interferon beta1a therapy changes lipoprotein metabolism in patients with
      multiple sclerosis.
AB  - To assess whether interferon beta1a (IFNbeta1a) therapy affects plasma
      lipoprotein metabolism, twelve patients with relapsing-remitting multiple
      sclerosis (MS) were studied during a two-year follow-up period. High density
      lipoprotein (HDL2) cholesterol and the HDL2/HDL3 ratio were increased at year 2
      and lipoprotein (a) was transitorily increased at year 1, in comparison to
      baseline levels. Apolipoprotein A-I was lower and apolipoprotein E higher at year
      1, only in a subgroup of patients who experienced relapses and/or progressed
      during therapy. These findings suggest that IFNbeta1a treatment is associated
      with changes in the lipoprotein metabolism. Alterations in this metabolism could
      be related to the immunomodulatory actions of the drug and the disease activity
      in multiple sclerosis patients.

PMID- 10905757
TI  - On-line analysis of electrolytes in extracorporeally circulating blood:
      application of a rat model to examine the effect of a single pharmacological dose
      of melatonin on electrolyte levels in blood.
AB  - An experimental model was developed to study the kinetics of electrolytes under
      different physiological and/or pathological conditions. The model was applied to
      investigate in vivo the effect of a pharmacological dose of melatonin on the
      concentrations of Ca2+, K+, Na+, and pH in the anticoagulated blood of
      anaesthetized male Wistar rats (250-350 g). After the application of 0.25 mg
      melatonin/kg body weight, injected intraperitoneally into each of 8 rats, the
      electrolytes were measured by a flow-through system with highly sensitive ion
      selective electrodes. The results were compared to a control group (n=8) which
      was treated with diluent (saline). The electrolytes were monitored continuously
      via an extracorporeal circulation, on-going for at least 60 min. Melatonin
      induced a significant increase of blood Ca2+ (p<0.02) by an average of 9.9% after
      60 min. However, total calcium concentration did not increase significantly. The
      extracorporeal circulation provoked an elevation of K+ by hemolysis. This K+
      increase was slightly diminished by melatonin (p<0.06). No melatonin effects were
      seen on Na+, pH and magnesium in blood and plasma, respectively. Also, the urine
      concentrations of the electrolytes were not altered by melatonin. The mechanism
      by which melatonin influences the blood concentrations of ionized calcium and
      potassium is not yet understood.

PMID- 10905758
TI  - Biochemical and hematological changes in low-level aluminum intoxication.
AB  - The aim of this study was to investigate the biochemical and hematological
      changes in patients on routine hemodialysis treatment when they were accidentally
      exposed to moderately high serum aluminum concentrations during a period of time
      of less than four months. We studied the changes in biochemical and hematological
      measurements in 33 patients on dialysis in our hospital before and during the
      exposure to about 0.85 pmol/l of aluminum in dialysis water due to a malfunction
      of the reverse osmosis system of water purification. Patients showed a decrease
      in the hemoglobin concentration from 115+/-12.4 g/l to 108+/-12.2 g/l (p=0.026)
      and in the mean corpuscular hemoglobin concentration from 5.15+/-0.22 to 5.02+/
      0.30 mmol/l (p=0.014). Ferritin was decreased from 243+/-192 microg/l to 196+/
      163 microg/l (p=0.047) and transferrin saturation from 0.20+/-0.06 to 0.15+/-0.07
      (p=0.004). Biochemical measurements related to calcium-phosphate metabolism did
      not change. Otherwise, all patients showed an increase in serum aluminum from
      0.56+/-0.44 to 1.63+/-0.52 micromol/l (p<0.001). No differences were detected in
      serum aluminum between patients receiving and not receiving oral aluminum salts.
      Even moderately high aluminum concentrations maintained during a short period of
      time could produce significant hematological alterations and a depletion of body
      iron stores before clinical manifestations were evident.

PMID- 10905759
TI  - On accuracy and precision of a HPLC method for measurement of urine porphyrin
      concentrations.
AB  - We studied the accuracy and precision of a HPLC method for determination of
      porphyrins in urine. A commercial standard solution appeared to contain less
      porphyrins than indicated by the manufacturer, since calibration resulted in
      lower concentrations of uroporphyrin and coproporphyrin: 16% and 8%,
      respectively. Coefficients of variation for the measurement of uro-, hepta-,
      copro I and copro III porphyrins in samples of patients with and without
      porphyria were often much less than 15%. Comparison of measurements with and
      without calibrated standards revealed differences for uroporphyrin and
      coproporphyrin of 27% and 5%, respectively. Recovery of added uroporphyrin and
      coproporphyrin was 99%. The main cause of the variability in test results was
      apparently the improperly calibrated standard solutions. The precision of
      porphyrin measurements was not influenced by the type of porphyria.

PMID- 10905760
TI  - Human heart-type cytoplasmic fatty acid-binding protein (H-FABP) for the
      diagnosis of acute myocardial infarction. Clinical evaluation of H-FABP in
      comparison with myoglobin and creatine kinase isoenzyme MB.
AB  - Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight
      cytoplasmic protein and present abundantly in the myocardium. When the myocardium
      is injured, as in the case of myocardial infarction, low molecular weight
      cytoplasmic proteins including H-FABP are released into the circulation and H
      FABP is detectable in a blood sample. We have already developed a direct sandwich
      ELISA for quantification of human H-FABP using two distinct types of monoclonal
      antibodies specific for human H-FABP. In this study we investigated the clinical
      validity of H-FABP as a biochemical diagnostic marker in the early phase of acute
      myocardial infarction (AMI). To evaluate the diagnostic usefulness of H-FABP in
      the early phase of AMI, blood samples were obtained from the following patients
      within 12 hours after the appearance of symptoms, and serum levels of H-FABP were
      compared with those of conventional diagnostic markers, such as myoglobin and
      creatine kinase isoenzyme MB (CK-MB). Blood samples were collected from patients
      with confirmed AMI (n=140), patients with chest pain who were afterwards not
      classified as AMI by normal CK-MB levels (non-AMI) (n=49) and normal healthy
      volunteers (n=75). The serum concentration of H-FABP was quantified with our
      direct sandwich-ELISA. The concentration of myoglobin mass was measured with a
      commercial RIA kit. The serum CK-MB activity was determined with an immuno
      inhibition assay kit. The overall sensitivity of H-FABP, within 12 hours after
      the appearance of symptoms, was 92.9%, while it was 88.6% with myoglobin and
      18.6% with CK-MB. The overall specificity of H-FABP was 67.3%, while it was 57.1%
      with myoglobin and 98.0% with CK-MB. The diagnostic efficacy rates with these
      markers were 86.2% (H-FABP), 80.4% (myoglobin) and 39.2% (CK-MB), respectively.
      The diagnostic validity of H-FABP was further assessed by receiver operating
      characteristic (ROC) curve analysis. The area under the curve (AUC) of H-FABP was
      0.921, which was significantly greater than with myoglobin (AUC: 0.843) and CK-MB
      (AUC: 0.654). These parameters, such as sensitivity, specificity, diagnostic
      efficacy and diagnostic accuracy, obtained for patients with chest pain within 3
      hours and/or 6 hours after the onset of symptoms were almost the same as those
      for patients within 12 hours after symptoms. H-FABP is more sensitive than both
      myoglobin and CK-MB, more specific than myoglobin for detecting AMI within 12
      hours after the onset of symptoms, and shows the highest values for both
      diagnostic efficacy and ROC curve analysis. Thus, H-FABP has great potential as
      an excellent biochemical cardiac marker for the diagnosis of AMI in the early
      phase.

PMID- 10905761
TI  - Quality control of coated antibodies: new, rapid determination of binding
      affinity.
AB  - A procedure is described for the determination of the affinity constant between a
      fluid-phase biotinylated antigen and a solid-phase monoclonal antibody. This
      procedure allows evaluation of the efficiency of an antibody as a coated tool for
      an immunoassay. For this purpose, the biotinylation of the antigen and its
      further quantitative measurement by streptavidin-peroxidase led to a single
      reversible interaction, the binding affinity of which greatly determines the
      quality of the assay. The free and bound fractions of the biotinylated antigen
      were obtained in wells coated with a low level of immobilized antibodies. At the
      equilibrium state, the free antigen present in the supernatant of these wells was
      further transferred to high level antibody coated wells which captured all the
      free antigen molecules. These molecules were quantified using a standard curve
      established with known concentrations of biotinylated antigen, also incubated in
      wells coated with the high level of antibody.

PMID- 10905762
TI  - Determination of reticulocytes: three methods compared.
AB  - Determination of reticulocytes in peripheral blood is a valuable tool for getting
      information about erythropoiesis of an individual. For many years, reticulocyte
      numbers were quantified manually by means of a microscope after staining with
      supravital dyes. However, this method is tedious and shows low reproducibility.
      Therefore, several methods for the automated determination of reticulocytes have
      been established in laboratory routine within the last years. The aim of this
      study was to compare three of these automated methods for reticulocyte analysis.
      Reticulocytes were determined in 130 subsequent routine samples by means of an
      ABX Pentra 120 Retic haematological analyser, a Coulter EPICS XL MCL flow
      cytometer and a Coulter STKS haematology system, using the fluorescent dye
      thiazole orange or the supravital dye new methylene blue for reticulocyte
      staining, respectively. The reticulocyte concentrations were slightly lower for
      the Coulter STKS haematology system (mean +/- SD 1.89+/-1.32%) when compared with
      the Coulter EPICS XL MCL flow cytometer or the ABX Pentra 120 Retic
      haematological analyser (2.11+/-1.25% and 2.12+/-1.15%, respectively). The
      correlations between all methods were significant (r(s) > or = 0.843, p < 0.001).
      Small intercepts were, however, observed in the correlation plots between the
      values obtained by means of the Coulter STKS haematology system and those
      obtained by the other two methods. Within-batch coefficients of variation were
      6.0%, 6.9% and 7.8% for the ABX Pentra 120 Retic haematological analyser, the
      Coulter STKS haematology system and the Coulter EPICS XL MCL flow cytometer,
      respectively. The corresponding between-batch coefficient of variation values
      were 6.8%, 4.9% and 5.3% as well as 14.1%, 7.6% and 6.1% for the low, medium and
      high control levels determined by means of the ABX Pentra 120 Retic
      haematological analyser and the Coulter STKS haematology system, respectively.
      These data suggest that all three methods allow the efficient and reliable
      determination of reticulocyte counts under clinical routine conditions. However,
      although the obtained data are very similar, differences exist which should be
      taken into account for the normal values of the different methods.

PMID- 10905763
TI  - A new modular chemiluminescence immunoassay analyser evaluated.
AB  - Thyrotropin (TSH), free thyroxine (fT4) and testosterone assays have been used as
      a probe to evaluate the performances of a new modular chemiluminescence (CL)
      immunoassay analyser, the Abbott Architect 2000. The evaluation was run in
      parallel on other systems that use CL as the detection reaction: DPC Immulite,
      Chiron Diagnostics ACS-180 and ACS Centaur (TSH functional sensitivity only). TSH
      functional sensitivity was 0.0012, 0.009, 0.033 and 0.039 mU/I for the Architect,
      Immulite, ACS Centaur and ACS-180, respectively. Testosterone functional
      sensitivity was 0.38, 3.7 and 2.0 nmol/l for Architect, Immulite and ACS-180,
      respectively. Good correlation was obtained between the ACS-180 and Architect for
      all assays. The Immulite correlation did not agree well with the Architect or ACS
      180 for fT4 and testosterone but was in good agreement for TSH. Regarding fT4 and
      testosterone, equilibrium dialysis and isotopic dilution gas-chromatography mass
      spectrometry (GC-MS) respectively were used as reference methods. For both within
      and between-run precision, the Architect showed the best reproducibility for all
      three analytes (CV < 6%).

PMID- 10905764
TI  - Point-of-care testing.

PMID- 10905765
TI  - Pre-analytical variation of laboratory variables.

PMID- 10905766
TI  - Autologous hematopoietic cell transplantation in Hodgkin's disease.
AB  - The use of HDT and AHCT in Hodgkin's disease patients with early relapsed and
      refractory disease is supported by historical comparisons. In regard to the late
      relapsed patient or the newly diagnosed high-risk patient, the role AHCT plays
      would ideally be answered by well-controlled phase 3 trials. A surrogate approach
      would be the comparison of AHCT data with well-matched historical controls. It is
      important, however, to be mindful of the changes that have occur red in the
      therapy of the newly diagnosed and relapsed HD patient (ABVD replacing MOPP
      regimens) and the impact these changes may or may not have on nonrelapse
      mortality in the autografted and nonautografted setting. In addition, the
      incorporation of consistent prognostic factors in any trial design may identify
      groups of relapsed or refractory and high-risk HD patients who may or may not
      gain benefit from HDT. The most effective and efficient route to answering these
      treatment questions is enrollment of patients in well-controlled and well
      designed clinical trials.

PMID- 10905767
TI  - Donor origin of circulating endothelial progenitors after allogeneic bone marrow
      transplantation.
AB  - Endothelial cell precursors circulate in blood and express antigens found on
      hematopoietic stem cells, suggesting that such precursors might be subject to
      transplantation. To investigate, we obtained adherence-depleted peripheral blood
      mononuclear cells from 3 individuals who had received a sex-mismatched allogeneic
      bone marrow transplant (BMT) and cultured the cells on fibronectin-coated plates
      with endothelial growth factors. The phenotype of the spindle-shaped cells that
      emerged in culture was characterized by immunofluorescent staining, and the
      origin of the cells was determined using a polymerase chain reaction (PCR)-based
      assay for polymorphic short tandem repeats (STRs). The cells manifested a number
      of endothelial characteristics-such as von Wlllebrand factor, CD31, and Flk-1/KDR
      expression; Bandeiraea simplicifolia lectin 1 binding; and acetylated low-density
      lipoprotein uptake-but lacked expression of certain markers of activation or
      differentiation, including intercellular adhesion molecule-1, vascular cell
      adhesion molecule-1, and the epitope for the anti-endothelial cell antibody
      P1H12. For each patient and at all time points studied (ranging from 5 to 52
      months after transplantation), STR-PCR analysis showed that cultured cells and
      nucleated blood cells came exclusively from the bone marrow donor. These results
      demonstrate that circulating endothelial progenitors are both transplantable and
      capable of long-term repopulation of human allogeneic BMT recipients.

PMID- 10905769
TI  - Granulocyte colony-stimulating factor given to donors before apheresis does not
      prevent aplasia in patients treated with donor leukocyte infusion for recurrent
      chronic myeloid leukemia after bone marrow transplantation.
AB  - We conducted 2 sequential studies of donor leukocyte infusion (DLI) in 26
      patients with chronic myeloid leukemia in hematologic relapse after unmodified
      allogeneic bone marrow transplantation. In the first study, cells for DLI were
      collected from 13 donors who were not treated with granulocyte colony-stimulating
      factor (G-CSF) (group 1). In the second study, cells were collected from 13
      donors who received G-CSF before apheresis (group 2) in an attempt to avoid
      aplasia after DLI. Patients in group 2 received 550-fold more CD34+ cells than
      those in group 1. We found no significant difference in the incidence (31% versus
      22%), onset time (41 vs. 48 days), or duration (15 vs. 14 days) of cytopenia
      after DLI in the 2 groups. G-CSF given to donors before collection of cells did
      not prevent aplasia. These findings support the hypothesis that the pathogenesis
      of aplasia after DLI is not restricted to the destruction of recipient
      hematopoietic cells but also involves failure of donor hematopoiesis by undefined
      mechanisms.

PMID- 10905768
TI  - Intentional induction of mixed chimerism and achievement of antitumor responses
      after nonmyeloablative conditioning therapy and HLA-matched donor bone marrow
      transplantation for refractory hematologic malignancies.
AB  - Mixed lymphohematopoietic chimerism can be induced in mice with bone marrow
      transplantation (BMT) after a nonmyeloablative preparative regimen that includes
      cyclophosphamide, anti-T-cell antibody therapy, and thymic irradiation. These
      mixed chimeras are resistant to the induction of graft-versus-host disease (GVHD)
      after delayed donor leukocyte infusions (DLIs), despite a potent
      lymphohematopoietic graft-versus-host reaction that converts the mixed chimeric
      state to a full donor one. Based on this animal model, we initiated a trial of
      nonmyeloablative therapy with HLA-matched or -mismatched donor BMT and DLI for
      refractory hematologic malignancies. Twenty-one of 36 patients enrolled in this
      trial received a genotypically (n = 20) or phenotypically (n = 1) HLA-matched
      donor transplant; results reported here are for those patients only. Preparative
      therapy consisted of cyclophosphamide in doses of 150 to 200 mg/kg;
      peritransplant antithymocyte globulin; thymic irradiation (in patients who had
      not received previous mediastinal radiation therapy); and cyclosporine. Eighteen
      of 20 evaluable patients developed persistent mixed lymphohematopoietic chimerism
      as defined by >1% donor peripheral white blood cells until at least day 35
      posttransplantation. Ten patients received prophylactic DLI beginning 5 to 6
      weeks after BMT for conversion of mixed chimerism to full donor hematopoiesis and
      to optimize a graft-versus-leukemia effect. Fourteen of 20 evaluable patients
      (70%) achieved an antitumor response; 8 of these responses were complete, and 6
      were partial. Of the 8 evaluable patients who received prophylactic DLI, 6 showed
      conversion to full donor chimerism. Five of the 9 evaluable patients (56%) who
      received prophylactic DLI achieved a complete response, compared with 3 of 11
      patients (27%) who did not receive prophylactic DLI. Currently 11 patients are
      alive, and 7 of these are free of disease progression at a median follow-up time
      of 445 days (range, 105-548 days) posttransplantation. Transplantation-related
      complications included cyclophosphamide-induced cardiac toxicity in 3 of 21
      patients (14%) and grade II or greater GVHD in 6 patients (29%). One patient (5%)
      died from a complication of BMT, and 1 patient (5%) died from GVHD after 2
      prophylactic DLIs were given for conversion of chimerism. In summary, mixed
      lymphohematopoietic chimerism was reproducibly induced after a novel
      nonmyeloablative preparative regimen incorporating chemotherapy, peritransplant
      antithymocyte globulin, and thymic irradiation, allowing for early administration
      of DLI in 10 of 21 patients. After treatment, striking antitumor responses were
      observed in the majority of patients with chemotherapy-refractory hematologic
      malignancies.

PMID- 10905770
TI  - Hydroxychloroquine for the treatment of chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) is a major complication of allogeneic
      bone marrow transplantation. Both the disease and the medications used to treat
      it are associated with significant morbidity and mortality. The manifestations of
      chronic GVHD often resemble those of autoimmune disorders. Hydroxychloroquine
      (HCQ) is a 4-aminoquinoline antimalarial drug used for the treatment of
      autoimmune diseases. HCQ interferes with antigen processing and presentation,
      cytokine production, and cytotoxicity and is synergistic with cyclosporine and
      tacrolimus in vitro. Forty patients with steroid-resistant or steroid-dependent
      chronic GVHD were enrolled in a phase 2 trial of HCQ 800 mg (12 mg/kg) per day.
      Three complete responses and 14 partial responses were seen in 32 evaluable
      patients (53% response rate). All responders tolerated a >50% reduction in their
      steroid dose while receiving HCQ. Clinical response occurred at a median of 8
      weeks (range, 4 to 24 weeks). No hematologic, hepatic, renal, or retinal toxicity
      was associated with HCQ. In light of its mechanisms of action, clinical activity
      for GVHD, and low toxicity profile, HCQ may be useful in a multiagent approach
      for the treatment of extensive chronic GVHD.

PMID- 10905771
TI  - Novobiocin in combination with high-dose chemotherapy for the treatment of
      advanced breast cancer: a phase 2 study.
AB  - We conducted the first phase 2 and pharmacologic study to evaluate the
      combination of novobiocin (a coumeromycin antibiotic that has been shown to
      augment alkylating agent cytotoxicity in experimental models) and high-dose
      cyclophosphamide and thiotepa followed by autologous marrow support in women with
      chemosensitive advanced breast cancer. Its aims were (1) to determine progression
      free survival (PFS) and overall survival (OS), (2) to evaluate the
      pharmacokinetics of cyclophosphamide and thiotepa, and (3) to measure the ability
      of novobiocin to reverse alkylator drug resistance in vitro. Forty-one women with
      chemotherapy-responsive advanced breast cancer received cyclophosphamide (4 g/m2)
      for peripheral blood stem cell mobilization (treatment 1) followed by high-dose
      cyclophosphamide (1.5 g/m2 per day for 4 days), thiotepa (200 mg/m2 per day for 4
      days), and novobiocin (4 g/day orally for 7 days) (treatment 2) and autologous
      marrow support. The median PFS was 10 months (range, 0.2-70.6 months) and OS,
      21.5 months (range, 0.2-70.6 months). There was no statistically significant
      relationship between PFS or OS and area-under-the-curve values of
      cyclophosphamide, thiotepa, or 4-hydroxycyclophosphamide. Patient plasma samples
      (n = 12) obtained during novobiocin therapy were able to reverse alkylator drug
      resistance in an in vitro colony-forming assay. Correlative laboratory studies in
      an in vitro model system demonstrated that patient plasma after novobiocin
      treatment resulted in the magnitude of resistance reversal that had been
      predicted by prior preclinical experiments. Clinically, however, this activity of
      novobiocin did not translate into a substantial increase in PFS or OS compared
      with historical controls treated with high-dose alkylator therapy alone.

PMID- 10905772
TI  - Effects of allogeneic bone marrow transplantation on recipient bone mineral
      density: A prospective study.
AB  - Allogeneic bone marrow transplant (BMT) recipients have many known risk factors
      for developing decreased bone mineral density (BMD) after transplantation. We
      performed a prospective sequential evaluation of BMD in the lumbar spine and
      nondominant hip using dual-energy x-ray absorptiometry (DEXA) in a cohort of 47
      adult patients (median age, 43 years) who were undergoing radiation-based BMT for
      hematologic malignancies. Baseline DEXA studies were performed before BMT and
      repeated at 3 to 4 months, 6 to 8 months, and 12 to 14 months after BMT. The
      majority of patients (60%) had been minimally treated with combination cytotoxic
      chemotherapy, having received no more than 1 treatment regimen before BMT. Graft
      versus-host disease prophylaxis consisted of cyclosporine in combination with
      either methotrexate or prednisone, or both. Mean lumbar spine and hip BMD were
      normal before BMT (spine: 1.01 g/cm2, z score = 96%; hip: 0.86 g/cm2, z score =
      100%) and gradually decreased (spine: 0.98 g/cm2, z score = 94%; hip: 0.76 g/cm2,
      z score = 91%) at 12 to 14 months. These declines were statistically significant
      (P < .006 and < .002 for lumbar spine; P < .001 and < .001 for hip). In addition,
      the sharpest decline occurred during the first 6 months after BMT and was more
      marked in the hip than the lumbar spine. These data suggest that BMT adversely
      affects BMD in this patient population.

PMID- 10905773
TI  - High-dose therapy with hematopoietic cell transplantation for patients with
      central nervous system involvement by non-Hodgkin's lymphoma.
AB  - Central nervous system (CNS) involvement by non-Hodgkin's lymphoma (NHL) carries
      a poor patient prognosis whether it occurs as a primary site of disease or
      secondarily in patients with systemic disease. In a group of 481 patients
      undergoing high-dose therapy with hematopoietic cell transplantation (HCT) for
      NHL, 15 patients (3.1%) were identified with CNS involvement. Two patients had
      primary CNS lymphoma, and 13 had secondary disease. All patients received
      intrathecal chemotherapy, and 13 received CNS radiotherapy before
      transplantation. Fourteen patients received systemic chemotherapy. At the time of
      transplantation, both patients with primary CNS lymphoma and 8 patients with
      secondary disease had achieved a complete response, 3 patients had achieved a
      partial response, 1 had failed induction therapy, and 1 had progression of CNS
      disease before high-dose therapy. Fourteen patients received carmustine,
      etoposide, and cyclophosphamide as the preparative regimen, and 1 patient
      received fractionated total body irradiation instead of carmustine. The 2
      patients with primary CNS lymphoma were alive and free of disease, 1 at 1,085
      days after HCT and 1 at 3,704 days after HCT. The actuarial 5-year event-free
      survival (EFS) was 46% +/- 26%, and overall survival (OS) was 41% +/- 28%. The
      median EFS and OS were 2.2 and 1.5 years, respectively. Three patients
      experienced symptomatic memory loss or intellectual decline after therapy, 1
      patient developed paraplegia, and 1 patient had a thrombotic stroke 20 months
      after HCT. Despite treatment-related toxicities, 7 patients responding to quality
      of-life questions at approximately 1 year after HCT gave their overall quality of
      life a median rating of 9 out of a possible 10 (range, 6-10). High-dose therapy
      with autologous HCT can produce extended EFS in patients with secondary CNS
      lymphoma and possibly in those with primary CNS NHL.

PMID- 10905774
TI  - The effect of accredited rural training tracks on physician placement.
AB  - Accredited family practice rural training tracks are placing graduates in rural
      settings at notably high rates: 76 percent overall and 88 percent among programs
      implemented in the past 10 years. Favorable, immediate results could be expected
      from their continuation and expansion, permitted by adjustments in the Balanced
      Budget Act of 1997.

PMID- 10905775
TI  - Responses to 'bending the rules to get a medication'.

PMID- 10905776
TI  - Responses to 'bending the rules to get a medication'.

PMID- 10905777
TI  - Responses to 'bending the rules to get a medication'.

PMID- 10905778
TI  - Responses to 'bending the rules to get a medication'.

PMID- 10905779
TI  - Getting the facts on restless legs.

PMID- 10905780
TI  - The importance of obtaining a sexual history.

PMID- 10905781
TI  - Interventional radiology in cancer patients.
AB  - Procedures performed by an interventional radiology specialist are becoming
      increasingly important in the management of patients with cancer. Although
      general interventional radiology procedures such as angiography and angioplasty
      are used in patients with and without cancer, certain procedures are reserved for
      the diagnosis and treatment of cancer or cancer-related complications.
      Interventional radiology procedures include imaging-guided biopsies to obtain
      samples for cytologic or pathologic testing without affecting adjacent
      structures. Transjugular liver biopsy is used to diagnose hepatic parenchymal
      abnormalities without traversing Glisson's capsule. This biopsy procedure is
      particularly useful in patients with coagulopathies. Because the transjugular
      liver biopsy obtains random samples, it is not recommended for biopsy of discrete
      hepatic masses. Fluid collections can also be sampled or drained using
      interventional radiology techniques. Transcatheter chemoembolization is a
      procedure that delivers a chemotherapeutic agent to a tumor along with sponge
      particles that have an ischemic effect on the mass. Tumor ablation, gene therapy
      and access of central veins for treatment are performed effectively under
      radiographic guidance. Cancer complications can also be treated with
      interventional radiology techniques. Examples include pain control procedures,
      vertebroplasty and drainage of obstructed organs. Interventional radiology
      techniques typically represent the least invasive definitive diagnostic or
      therapeutic options available for patients with cancer. They can often be
      performed at a lower cost and with less associated morbidity than other
      interventions.

PMID- 10905782
TI  - Restless legs syndrome: detection and management in primary care. National Heart,
      Lung, and Blood Institute Working Group on Restless Legs Syndrome.
AB  - Restless legs syndrome (RLS) is a neurologic movement disorder that is often
      associated with a sleep complaint. Patients with RLS have an irresistible urge to
      move their legs, which is usually due to disagreeable sensations that are worse
      during periods of inactivity and often interfere with sleep. It is estimated that
      between 2 and 15 percent of the population may experience symptoms of RLS.
      Primary RLS likely has a genetic origin. Secondary causes of RLS include iron
      deficiency, neurologic lesions, pregnancy and uremia. RLS also may occur
      secondarily to the use of certain medications. The diagnosis of RLS is based
      primarily on the patient's history. A list of questions that may be used as a
      basis to assess the likelihood of RLS is included in this article. Pharmacologic
      treatment of RLS includes dopaminergic agents, opioids, benzodiazepines and
      anticonvulsants. The primary care physician plays a central role in the diagnosis
      and management of RLS.

PMID- 10905783
TI  - Health issues in men: Part II. Common psychosocial disorders.
AB  - During screening examinations and, when appropriate, other health-related visits,
      family physicians should be alert for signs and symptoms of common psychosocial
      disorders in men. Health issues of concern include alcohol and substance abuse,
      domestic violence, midlife crisis and depression. Alcohol remains the most abused
      drug in America. The highest rates of alcohol abuse are in men 25 to 39 years of
      age, although alcoholism is also a considerable problem after 65 years of age.
      Disulfiram and the opioid antagonist naltrexone are the two medications currently
      labeled by the U.S. Food and Drug Administration for the treatment of chronic
      alcohol dependence. Like alcohol abuse, domestic violence is a sign of
      psychosocial distress in men. Domestic violence may be a problem in up to 16
      percent of marriages. Most men move through the midlife period without
      difficulty. Major depressive illness occurs in about 1 percent of elderly men,
      whereas minor depression or subsyndromal depression affects 13 to 27 percent of
      older men. Selective serotonin reuptake inhibitors have become first-line therapy
      for depression.

PMID- 10905784
TI  - Female sexual dysfunction: evaluation and treatment.
AB  - Sexual dysfunction includes desire, arousal, orgasmic and sex pain disorders
      (dyspareunia and vaginismus). Primary care physicians must assume a proactive
      role in the diagnosis and treatment of these disorders. Long-term medical
      diseases, minor ailments, medications and psychosocial difficulties, including
      prior physical or sexual abuse, are etiologic factors. Gynecologic maladies and
      cancers (including breast cancer) are also frequent sources of sexual
      dysfunction. Patient education and reassurance, with early diagnosis and
      intervention, are essential for effective treatment. Patient history and physical
      examination techniques, normal sexual responses and the factors that influence
      these responses, and the application of medical and gynecologic treatments to
      sexual issues are discussed. Basic treatment strategies, which may be
      successfully provided by primary care physicians for most sexual dysfunctions,
      are outlined. Referral can be reserved for patients who do not respond to
      therapy.

PMID- 10905785
TI  - Management of aphthous ulcers.
AB  - Aphthous ulcers are a common and painful problem. Benign aphthae tend to be small
      (less than 1 cm in diameter) and shallow. Aphthous ulcers that occur in
      conjunction with symptoms of uveitis, genital ulcerations, conjunctivitis,
      arthritis, fever or adenopathy should prompt a search for a serious etiology. The
      lack of clarity regarding the etiology of aphthous ulcers has resulted in
      treatments that are largely empiric. These treatments include antibiotics, anti
      inflammatories, immune modulators, anesthetics and alternative (herbal) remedies.

PMID- 10905786
TI  - Diagnosis and management of acute pancreatitis.
AB  - Acute pancreatitis usually occurs as a result of alcohol abuse or bile duct
      obstruction. A careful review of the patient's history and appropriate laboratory
      studies can help the physician identify the etiology of the condition and guide
      management. Serum amylase and lipase levels are still used to confirm the
      diagnosis of acute pancreatitis. Although not routinely available, the serum
      trypsin level is the most accurate laboratory indicator for pancreatitis.
      Ultrasonography, computed tomography and endoscopic retrograde
      cholangiopancreatography are additional modalities that can help the family
      physician choose the best treatment approach. Prompt identification of patients
      who need intensive care referral or subspecialty consultation is crucial. The
      APACHE II and the multiple organ system failure scales provide prognostic
      information at the time of admission and may be repeated daily to monitor disease
      progression. Therapies such as nasogastric suctioning, anticholinergics and
      histamine H2-receptor blockers have not been shown to decrease symptoms or
      hospital stays in patients with acute pancreatitis. Systemic antibiotics have
      been found to improve outcome in patients with severe disease. With supportive
      care, most patients have a good clinical outcome.

PMID- 10905787
TI  - Photo quiz. More than just a comet...benign familial pemphigus.

PMID- 10905788
TI  - AIDS Society recommendations for antiretroviral therapy.

PMID- 10905789
TI  - ACIP issues recommendations for the 2000-2001 influenza season. Advisory
      Committee on Immunization Practices.

PMID- 10905790
TI  - A daughter who won't let her mother go.

PMID- 10905791
TI  - My experiences at an 'orphan' school: the importance of finding 'parents'.

PMID- 10905792
TI  - Screening for adolescent idiopathic scoliosis.

PMID- 10905793
TI  - The vascular sciences in the age of information.

PMID- 10905794
TI  - A clinical approach to the management of the patient with coronary (Co) and/or
      carotid (Ca) artery disease who presents with leg ischaemia (Lis).
AB  - The purpose of this document is to provide the clinician with easy-to-use
      guidelines when faced with a patient with severe ischaemia in the limbs requiring
      interventional treatment; the CoCaLis document does not focus on the management
      of the lower limb ischaemia, but rather on the best possible approach to the
      associated coronary and/or carotid artery disease. The first part of the text
      deals with the epidemiological aspects of this condition followed by a
      description of, and proposals for, the management of risk factors. The next part
      deals with the approach to the coronary circulation and the carotid territory. In
      each part attention is mainly given to the practical aspects in terms of both
      diagnosis and treatment; for each of these steps the costs involved are
      considered and attention given to balancing the clinical decisions against the
      costs. The recommendations given are 'evidence based' when such evidence exists
      and, if not, the proposals are based on the consensus of the members of the
      group. In many instances it was apparent that the necessary information is not
      available in the literature. The authors hope that the CoCaLis document may not
      only improve the management of the vascular patient but also stimulate further
      research in this difficult clinical condition which carries a significantly
      increased risk for the patient.

PMID- 10905795
TI  - Pharmacokinetics of argatroban in primates: evidence on endogenous uptake.
AB  - BACKGROUND: Antithrombin agent, argatroban, is currently undergoing several
      clinical trials for cardiovascular indications. Because of its solubility, this
      drug is usually administered via an intravenous bolus followed by infusion. The
      purpose of this study was to determine the pharmacokinetics of argatroban after
      intravenous bolus injection in primates. METHODS: Parallel in vitro studies in
      primate whole blood were carried out to simulate a one-compartment system.
      Argatroban (range 1.0-7.5 mg/kg) was administered to four groups of primates and
      blood samples were drawn at various time periods. Argatroban measurements were
      made in plasma using functional (aPTT, Heptest, TT) and HPLC methods. RESULTS: In
      vitro, argatroban primarily distributed in the plasma in proportionate amounts.
      Relative uptake of argatroban to the blood cells (leukocytes and erythrocytes)
      was minimum. However, in vivo, argatroban followed a complex pharmacokinetics.
      Within 5 min after the bolus administration, only <20% of argatroban was
      recovered. The recovered amount was proportionate to the dosage and followed the
      expected kinetics with a half-life of <20 min. Simultaneous quantitation of M1
      metabolite of argatroban revealed only a fraction of recovered argatroban
      (approximately 25%) converted into M1 in these experimental settings. Results
      obtained from the functional and absolute methods correlated well. HPLC profile
      did not reveal the presence of any other metabolite(s). CONCLUSIONS: These
      observations suggest that argatroban may be endogenously taken up by the vascular
      or other sites and may exhibit a complex kinetics. In acute settings, the
      metabolic transformation of argatroban to M1 is relatively low. To further
      clarify the pharmacokinetics/pharmacodynamics of this drug, additional studies
      are warranted.

PMID- 10905796
TI  - Microvascular blood is distributed more to venules than to arterioles in patients
      with Buerger's disease. Observation of bulbar conjunctiva by intravital
      microscope system.
AB  - BACKGROUND: It has been a matter of controversy whether abnormalities of organs
      other than extremities may be a clinical manifestation of Buerger's disease
      (thromboangiitis obliterans; TAO). In the present investigation, our aim was to
      quantitatively characterise the configuration of microvascular networks in bulbar
      conjunctiva, which is not affected apparently, in patients with thromboangiitis
      obliterans. METHODS: Nine men with thromboangiitis obliterans attended our
      hospital and nine male volunteers as normal controls were enrolled in this study.
      We observed and analysed the configuration of the network of a bulbar conjunctiva
      by use of intravital microscope system with computer assisted image processing
      functions. Microvessel density was defined as a summation of vessel length in a
      ROI area and tortuosity was evaluated by a ratio of vessel length to direct
      distance of both terminals. RESULTS: In the microcirculation of bulbar
      conjunctiva in thromboangiitis obliterans, arteriole diameter was significantly
      decreased and density of venules was significantly increased. Increased venular
      density was mainly explained by increased tortuosity of venules. CONCLUSIONS:
      Consequently, microvascular blood was distributed more to venules than to
      arterioles in patients with thromboangiitis obliterans. Venule/arteriole ratios
      of diameter, tortuosity and microvessel density may be useful parameters to
      characterize the configuration of microvascular networks in thromboangiitis
      obliterans.

PMID- 10905797
TI  - Smooth muscle cell migration induced by shear-loaded platelets and endothelial
      cells. Enhanced platelet-derived growth factor production by shear-loaded
      platelets.
AB  - BACKGROUND: Uncontrolled migration and proliferation of smooth muscle cells (SMC)
      are the main mechanisms of development of atherosclerotic neointima. However, it
      has not yet been elucidated how mechanical stress is involved in this process. We
      investigated smooth muscle cell mitogenic activity induced by shear-loaded
      platelets and endothelial cells. METHODS:  EXPERIMENTAL DESIGN: in vitro
      experimental study. We devised four types of conditioned media; supernatant of
      mixed culture of platelets and endothelial cell (ST), supernatant of shear-loaded
      mixed culture of platelets and endothelial cell (SH), ST medium neutralised with
      anti-PDGF antibody (ST+), and SH medium neutralised with anti-PDGF antibody
      (SH+). Smooth muscle cells were cultured in each conditioned medium, and their
      spreading activity was determined under a microscope. RESULTS: Smooth muscle
      cells spreading activity in the SH group was significantly greater than that in
      the ST group. Their spreading activity was suppressed by anti-PDGF antibody under
      shear conditions (SH+), but it was not by anti-PDGF antibody under static
      conditions (ST+). CONCLUSIONS: Our results demonstrate that platelet-derived
      growth factor is produced by shear-loaded platelets and endothelial cells, and
      local mechanical forces may play an important role in cardiovascular disease.

PMID- 10905798
TI  - Platelet surface P-selectin molecules increased after exposing platelet to a high
      shear flow.
AB  - BACKGROUND: P-selectin is known to play a crucial role in leucocyte recruitment
      at sites of vascular injury. Although platelet surface expression of P-selectin
      molecules are well known to occur after platelet stimulation by chemical agonists
      such as alpha-thrombin, it is still uncertain whether P-selectin expression
      occurs in the process of the more physiological platelet activation pathway
      mediated by interaction between von Willebrand factor (vWF) and platelet receptor
      proteins, including glycoprotein (GP) Ibalpha and GP IIb/IIIa, occurring under
      high shear rates generated by blood flow. METHODS: We have developed a method to
      detect P-selectin molecules expressed on platelet surface with flow-cytometer and
      monoclonal antibody, which can bind exclusively to P-selectin (WGA1), directly
      conjugated with fluorescein isothiocynate. This method allowed us to measure
      platelet surface P-selectin molecules semiquantitatively. RESULTS: We
      demonstrated that a significant increase in platelet surface P-selectin molecules
      occur after exposing platelets to a relatively high shear rate of 10,800 s(-1).
      We have also demonstrated that shear-induced surface expression of P-selectin as
      well as microparticle release from platelets depended at least on the interaction
      between von Willebrand factor and glycoprotein Ibalpha, a platelet surface
      receptor for the former. CONCLUSIONS: Shear-induced von Willebrand-mediated
      surface expression of P-selectin may play a role in leucocyte recruitment in
      platelet thrombi at vascular injury sites.

PMID- 10905799
TI  - A comparative study of iliac and abdominal aortic aneurysms.
AB  - BACKGROUND: The aim of the paper is to compare the epidemiology, risk factors and
      manifestations of iliac and abdominal aortic aneurysms. METHODS: Two studies were
      used: 1. 5,470 65-73-year-old men invited for screening for abdominal aortic
      aneurysms. 2. Review of all 350 patients operated on for central aneurysms in the
      county of Viborg, Denmark from 1989-1997. RESULTS: 4,176 attended for screening.
      One hundred and seventy (4.0%) had an abdominal aortic aneurysm. Twenty-one
      (0.56%) needed operation. The proportion of patients with common iliac aneurysms
      requiring surgery was 0.17%. The operative incidence of iliac aneurysm was 18.4
      per million per year, and 92.4 per million per year were operated on for
      abdominal aortic aneurysm. The mean serum cholesterol level for isolated iliac
      aneurysm and combined aneurysms was significantly lower compared to isolated
      abdominal aortic aneurysm (p<0.05). Urological symptoms were present in 42% of
      cases with isolated iliac aneurysm, and 25% of combined aneurysms compared to 8%
      of isolated abdominal aortic aneurysms. Fifty-eight percent of the isolated iliac
      aneurysms were ruptured, as against 27% of the abdominal aortic aneurysms. The
      peri- and postoperative mortality was 57% in ruptured isolated iliac aneurysms,
      47% in ruptured combined aneurysms, and 31% in ruptured isolated aortic
      aneurysms. CONCLUSIONS: Iliac aneurysms seem to be more underdiagnosed than
      abdominal aortic aneurysms, and are often diagnosed because of clinical
      manifestations, especially urological, or rupture. Iliac aneurysms seem more
      lethal than those of the abdominal aorta in cases of rupture.

PMID- 10905800
TI  - Does in situ replacement of a staphylococcal infected vascular graft with a
      rifampicin impregnated gelatin sealed Dacron graft reduce the incidence of
      subsequent infection?
AB  - BACKGROUND: The aim of this study was to treat methicillin-resistant
      Staphylococcus aureus (MRSA) or S. epidermidis prosthetic vascular graft
      infections by in situ replacement with a rifampicin bonded Gelsoft graft.
      METHODS: Interposition grafts were placed in the carotid artery of 56 sheep and
      the graft surface directly inoculated with 10(8) colony forming units of MRSA or
      S. epidermidis. At three weeks, grafts were harvested and sheep allocated to
      three groups. In the MRSA group, sheep received grafts soaked in 1.2 mg/ml (12),
      10 mg/ml (10) and no rifampicin (7). For S. epidermidis, sheep received grafts
      soaked in 1.2 mg/ml (10), 10 mg/ml (9) and no rifampicin (8). There were two
      deaths, in the MRSA study group. Remaining sheep were euthanased and grafts
      harvested three weeks following regrafting. Swabs were taken to assess bacterial
      growth in the perigraft tissues, and external and internal graft surfaces. A 3-5
      mm segment of graft was incubated in broth medium. RESULTS: For MRSA, no
      statistical difference between the groups was reached for any of the measured
      parameters. For S. epidermidis, a significant reduction was reached for total
      infected specimens in the 10 mg/ml group compared to both control (p<0.001) and
      1.2 mg/ml (p<0.005) groups. Graft re-infection was also less likely to occur with
      S. epidermidis than MRSA. CONCLUSIONS: Replacement of S. epidermidis infected
      vascular grafts with 10 mg/ml rifampicin soaked Gelsoft graft is effective in
      reducing subsequent S. epidermidis infection. This conclusion cannot be extended
      to MRSA infected vascular grafts.

PMID- 10905801
TI  - Pathological changes of hepatic artery and portal vein, after allyl-alcohol and
      carbon tetrachloride administration. An experimental study.
AB  - BACKGROUND: Allyl-alcohol (AA) and carbon tetrachloride (CC14) are known to cause
      peritoneal and pericentral liver necrosis, respectively. This study investigates
      pathological changes of hepatic artery and portal vein after simultaneous
      administration of AA and CC14 in rats. METHODS: The study comprised 130 male
      Wistar rats divided randomly into 2 groups: I (n=10) sham and II (n=120) AA
      injection (intraperitoneally: 0.62 mmol/kg) and rhinogastric administration of
      CC14 (0.66 ml/kg, 1:1 volume dilution in corn oil). After injection was
      completed, animals of group II were assigned in 12 categories and sacrificed 2,
      4, 6, 12, 18, 24, 33, 48, 57, 81, and 153 hrs after. Tissue was obtained from the
      left anterior lobe and the hilum of the liver, and histological examination
      included H&E, silver methenamine and van Giesson stains. RESULTS: Liver sections
      from group II (AA+CC14) demonstrated periportal together with pericentral
      necrosis; the peak was 57 hrs after injection. In all 120 cases, H&E stain showed
      evidence of regeneration originated from zone 2, extending to zone 1 and
      occasionally to zone 3, and accomplished mainly by non-necrotic cell
      proliferation. Sections from the liver hilum showed thrombosis of the portal
      vein, whereas the hepatic artery and its branches developed a variety of changes.
      Initially (2, 4 hrs), endothelial hypertrophy was observed which was followed by
      focal fibrinoid necrosis of the arterial wall (6 hrs). Later on (9-153 hrs) the
      following findings were present: hyperplasia and non-isometric cytoplasmic
      vacuolisation of media, disruption of the elastic lamina, aggregation of foam
      cells and macrophages in intima, media, and focally in adventitia of hepatic
      artery; and lymphocytic inflammation of intimal and periadventitial area. In 2
      cases (153 hrs) hepatic artery thrombosis was present. CONCLUSIONS: Additionally
      to liver parenchymal changes, simultaneous administration of allyl-alcohol and
      carbon tetrachloride in rats results to vascular changes mainly in the hepatic
      artery and its branches. During liver parenchymal regeneration, the hepatic
      artery and its branches develop microscopic features that morphologically
      resemble those of atherosclerosis. These changes may result in hepatic artery
      thrombosis and or obstruction.

PMID- 10905802
TI  - Elevated levels of soluble E-selectin in diabetic patients with severe
      symptomatic peripheral arterial occlusive disease requiring angioplasty. A
      possible role in diabetic vascular disease?
AB  - BACKGROUND: To study levels of E-selectin in patients with peripheral arterial
      occlusive disease who were undergoing percutaneous transluminal angioplasty.
      METHODS: Experimental design and setting: Cross sectional case control study,
      conducted in a teaching hospital. SUBJECTS: Seven patients with type-2 (non
      insulin dependent) diabetes mellitus undergoing transluminal angioplasty for
      symptomatic peripheral arterial occlusive disease, had blood tests for sE
      selectin measurement, and were compared to a similar groups of age and sex
      matched non-diabetic patients with arteriopathy who are undergoing the same
      procedure. Also evaluated were a group of diabetic patients and healthy non
      diabetics with no peripheral arterial disease. RESULTS: The levels of sE-selectin
      in the two diabetic groups were significantly higher than the non-diabetic groups
      measuring at 77 ng/ml (53-120) and 79 ng/ml (43-98) (median, range) vs 54 ng/ml
      (24-104) in the non-diabetic with arteriopathy, and 42 ng/ml (35-66) in the
      normal healthy controls, p<0.04, p<0.003 respectively, Mann Whitney "U" test.
      CONCLUSIONS: We have demonstrated significantly high values of soluble E-selectin
      in patients with diabetes mellitus requiring angioplasty for symptomatic
      peripheral arterial occlusive disease. This suggests that sE-selectin may be
      involved in the diabetic angiopathic process. It may act as a precursor for
      smooth muscle proliferation.

PMID- 10905803
TI  - Pharmacological assessment of adrenergic receptors in human varicose veins.
AB  - BACKGROUND: Experiments were to characterize pharmacologically adrenergic
      receptors in human varicose veins to the natural transmitter norepinephrine and
      to an extract of Ruscus. METHODS: Greater saphenous veins and varicose
      tributaries from patients undergoing elective surgery for primary varicose
      disease and portions of greater saphenous veins from patients undergoing
      peripheral arterial reconstruction (control) were suspended for the measurement
      of isometric force in organ chambers. Concentration response curves were obtained
      to norepinephrine or the extract of Ruscus aculeatus in the absence and presence
      of selective antagonists of alpha, and alpha2 adrenergic receptors. RESULTS:
      Norepinephrine and Ruscus extract caused concentration-dependent contractions in
      all veins. Contractions to norepinephrine were greater in control veins than in
      varicose tributaries. Contractions to the extract were greater in varicose
      tributaries than in greater saphenous veins from varicose patients. Contractions
      to norepinephrine were reduced similarly by alpha and alpha2-adrenergic agonists
      in control and varicose veins but to a greater extent by alpha2-blockade in
      greater saphenous veins from varicose patients. Contractions to Ruscus extract
      were not reduced by alpha-adrenergic blockade in control veins but were reduced
      by alpha2-adrenergic blockade in varicose veins. CONCLUSIONS: These results
      suggest a differential distribution of alpha adrenergic receptors on greater
      saphenous veins from non-varicose patients compared to those with primary
      varicose disease. Venotropic agents from plant extract probably exert effects by
      way of multiple receptor and non-receptor mediated events.

PMID- 10905804
TI  - The process of writing a scientific paper.

PMID- 10905805
TI  - Expanding NEURON's repertoire of mechanisms with NMODL.
AB  - Neuronal function involves the interaction of electrical and chemical signals
      that are distributed in time and space. The mechanisms that generate these
      signals and regulate their interactions are marked by a rich diversity of
      properties that precludes a "one size fits all" approach to modeling. This
      article presents a summary of how the model description language NMODL enables
      the neuronal simulation environment NEURON to accommodate these differences.

PMID- 10905806
TI  - Latent attractors: a model for context-dependent place representations in the
      hippocampus.
AB  - Cells throughout the rodent hippocampal system show place-specific patterns of
      firing called place fields, creating a coarse-coded representation of location.
      The dependencies of this place code--or cognitive map--on sensory cues have been
      investigated extensively, and several computational models have been developed to
      explain them. However, place representations also exhibit strong dependence on
      spatial and behavioral context, and identical sensory environments can produce
      very different place codes in different situations. Several recent studies have
      proposed models for the computational basis of this phenomenon, but it is still
      not completely understood. In this article, we present a very simple
      connectionist model for producing context-dependent place representations in the
      hippocampus. We propose that context dependence arises in the dentate gyrus-hilus
      (DGH) system, which functions as a dynamic selector, disposing a small group of
      granule and pyramidal cells to fire in response to afferent stimulus while
      depressing the rest. It is hypothesized that the DGH system dynamics has "latent
      attractors," which are unmasked by the afferent input and channel system activity
      into subpopulations of cells in the DG, CA3, and other hippocampal regions as
      observed experimentally. The proposed model shows that a minimally structured
      hippocampus-like system can robustly produce context-dependent place codes with
      realistic attributes.

PMID- 10905807
TI  - The approach of a neuron population firing rate to a new equilibrium: an exact
      theoretical result.
AB  - The response of a noninteracting population of identical neurons to a step change
      in steady synaptic input can be analytically calculated exactly from the
      dynamical equation that describes the population's evolution in time. Here, for
      model integrate-and-fire neurons that undergo a fixed finite upward shift in
      voltage in response to each synaptic event, we compare the theoretical prediction
      with the result of a direct simulation of 90,000 model neurons. The degree of
      agreement supports the applicability of the population dynamics equation. The
      theoretical prediction is in the form of a series. Convergence is rapid, so that
      the full result is well approximated by a few terms.

PMID- 10905808
TI  - Formation of direction selectivity in natural scene environments.
AB  - Most simple and complex cells in the cat striate cortex are both orientation and
      direction selective. In this article we use single-cell learning rules to develop
      both orientation and direction selectivity in a natural scene environment. We
      show that a simple principal component analysis rule is inadequate for developing
      direction selectivity, but that the BCM rule as well as similar higher-order
      rules can. We also demonstrate that the convergence of lagged and nonlagged cells
      depends on the velocity of motion in the environment, and that strobe rearing
      disrupts this convergence, resulting in a loss of direction selectivity.

PMID- 10905809
TI  - A phase model of temperature-dependent mammalian cold receptors.
AB  - We present a tractable stochastic phase model of the temperature sensitivity of a
      mammalian cold receptor. Using simple linear dependencies of the amplitude,
      frequency, and bias on temperature, the model reproduces the experimentally
      observed transitions between bursting, beating, and stochastically phase-locked
      firing patterns. We analyze the model in the deterministic limit and predict,
      using a Strutt map, the number of spikes per burst for a given temperature. The
      inclusion of noise produces a variable number of spikes per burst and also
      extends the dynamic range of the neuron, both of which are analyzed in terms of
      the Strutt map. Our analysis can be readily applied to other receptors that
      display various bursting patterns following temperature changes.

PMID- 10905810
TI  - The number of synaptic inputs and the synchrony of large, sparse neuronal
      networks.
AB  - The prevalence of coherent oscillations in various frequency ranges in the
      central nervous system raises the question of the mechanisms that synchronize
      large populations of neurons. We study synchronization in models of large
      networks of spiking neurons with random sparse connectivity. Synchrony occurs
      only when the average number of synapses, M, that a cell receives is larger than
      a critical value, Mc. Below Mc, the system is in an asynchronous state. In the
      limit of weak coupling, assuming identical neurons, we reduce the model to a
      system of phase oscillators that are coupled via an effective interaction, gamma.
      In this framework, we develop an approximate theory for sparse networks of
      identical neurons to estimate Mc analytically from the Fourier coefficients of
      gamma. Our approach relies on the assumption that the dynamics of a neuron depend
      mainly on the number of cells that are presynaptic to it. We apply this theory to
      compute Mc for a model of inhibitory networks of integrate-and-fire (I&F) neurons
      as a function of the intrinsic neuronal properties (e.g., the refractory period
      Tr), the synaptic time constants, and the strength of the external stimulus,
      Iext. The number Mc is found to be nonmonotonous with the strength of Iext. For
      Tr = 0, we estimate the minimum value of Mc over all the parameters of the model
      to be 363.8. Above Mc, the neurons tend to fire in smeared one-cluster states at
      high firing rates and smeared two-or-more-cluster states at low firing rates.
      Refractoriness decreases Mc at intermediate and high firing rates. These results
      are compared to numerical simulations. We show numerically that systems with
      different sizes, N, behave in the same way provided the connectivity, M, is such
      that 1/Meff = 1/M - 1/N remains constant when N varies. This allows extrapolating
      the large N behavior of a network from numerical simulations of networks of
      relatively small sizes (N = 800 in our case). We find that our theory predicts
      with remarkable accuracy the value of Mc and the patterns of synchrony above Mc,
      provided the synaptic coupling is not too large. We also study the strong
      coupling regime of inhibitory sparse networks. All of our simulations demonstrate
      that increasing the coupling strength reduces the level of synchrony of the
      neuronal activity. Above a critical coupling strength, the network activity is
      asynchronous. We point out a fundamental limitation for the mechanisms of
      synchrony relying on inhibition alone, if heterogeneities in the intrinsic
      properties of the neurons and spatial fluctuations in the external input are also
      taken into account.

PMID- 10905811
TI  - A neural network architecture for visual selection.
AB  - This article describes a parallel neural net architecture for efficient and
      robust visual selection in generic gray-level images. Objects are represented
      through flexible star-type planar arrangements of binary local features which are
      in turn star-type planar arrangements of oriented edges. Candidate locations are
      detected over a range of scales and other deformations, using a generalized Hough
      transform. The flexibility of the arrangements provides the required invariance.
      Training involves selecting a small number of stable local features from a
      predefined pool, which are well localized on registered examples of the object.
      Training therefore requires only small data sets. The parallel architecture is
      constructed so that the Hough transform associated with any object can be
      implemented without creating or modifying any connections. The different object
      representations are learned and stored in a central module. When one of these
      representations is evoked, it "primes" the appropriate layers in the network so
      that the corresponding Hough transform is computed. Analogies between the
      different layers in the network and those in the visual system are discussed.
      Furthermore, the model can be used to explain certain experiments on visual
      selection reported in the literature.

PMID- 10905812
TI  - Using Bayes' rule to model multisensory enhancement in the superior colliculus.
AB  - The deep layers of the superior colliculus (SC) integrate multisensory inputs and
      initiate an orienting response toward the source of stimulation (target).
      Multisensory enhancement, which occurs in the deep SC, is the augmentation of a
      neural response to sensory input of one modality by input of another modality.
      Multisensory enhancement appears to underlie the behavioral observation that an
      animal is more likely to orient toward weak stimuli if a stimulus of one modality
      is paired with a stimulus of another modality. Yet not all deep SC neurons are
      multisensory. Those that are exhibit the property of inverse effectiveness:
      combinations of weaker unimodal responses produce larger amounts of enhancement.
      We show that these neurophysiological findings support the hypothesis that deep
      SC neurons use their sensory inputs to compute the probability that a target is
      present. We model multimodal sensory inputs to the deep SC as random variables
      and cast the computation function in terms of Bayes' rule. Our analysis suggests
      that multisensory deep SC neurons are those that combine unimodal inputs that
      would be more uncertain by themselves. It also suggests that inverse
      effectiveness results because the increase in target probability due to the
      integration of multisensory inputs is larger when the unimodal responses are
      weaker.

PMID- 10905814
TI  - New support vector algorithms
AB  - We propose a new class of support vector algorithms for regression and
      classification. In these algorithms, a parameter nu lets one effectively control
      the number of support vectors. While this can be useful in its own right, the
      parameterization has the additional benefit of enabling us to eliminate one of
      the other free parameters of the algorithm: the accuracy parameter epsilon in the
      regression case, and the regularization constant C in the classification case. We
      describe the algorithms, give some theoretical results concerning the meaning and
      the choice of nu, and report experimental results.

PMID- 10905813
TI  - Choice and value flexibility jointly contribute to the capacity of a subsampled
      quadratic classifier
AB  - Biophysical modeling studies have suggested that neurons with active dendrites
      can be viewed as linear units augmented by product terms that arise from
      interactions between synaptic inputs within the same dendritic subregions.
      However, the degree to which local nonlinear synaptic interactions could augment
      the memory capacity of a neuron is not known in a quantitative sense. To approach
      this question, we have studied the family of subsampled quadratic classifiers:
      linear classifiers augmented by the best k terms from the set of K = (d2 + d)/2
      second-order product terms available in d dimensions. We developed an expression
      for the total parameter entropy, whose form shows that the capacity of an SQ
      classifier does not reside solely in its conventional weight values-the explicit
      memory used to store constant, linear, and higher-order coefficients. Rather, we
      identify a second type of parameter flexibility that jointly contributes to an SQ
      classifier's capacity: the choice as to which product terms are included in the
      model and which are not. We validate the form of the entropy expression using
      empirical studies of relative capacity within families of geometrically
      isomorphic SQ classifiers. Our results have direct implications for
      neurobiological (and other hardware) learning systems, where in the limit of high
      dimensional input spaces and low-resolution synaptic weight values, this
      relatively little explored form of choice flexibility could constitute a major
      source of trainable model capacity.

PMID- 10905815
TI  - The effect of lecithin supplementation on the biochemical profile and
      morphological changes in the liver of rats fed different animal fats.
AB  - Sixty-four Wistar rats were divided into 8 equal groups and kept for 36 days in
      individual boxes. Three of the groups were given full synthetic diets containing
      various animal fats: beef tallow, pork fat or fish oil. A control group was fed
      the diets without the fat. The other four groups were fed the same diets with
      lecithin supplementation. At the end of experiment, sections taken from the liver
      were stained with haematoxylin eosin and Sudan III to indicate fat infiltration.
      Liver enzyme levels, total bilirubin, albumin and two products of lipid
      metabolism were measured in serum from all the animals. The addition of lecithin
      to the diets did not influence the level of enzymes in the serum except in rats
      fed the diet containing beef tallow. A relationship between the type of diet,
      lecithin supplementation and the total cholesterol concentration in serum was
      observed. The concentration of HDL-cholesterol was only influenced by lecithin
      supplementation and that of triglycerides by the type of fat in the diet. The
      addition of lecithin to the diet was associated with proliferation of Kupffer
      cells, and an increased number of binuclear cells. Fatty degeneration of
      hepatocytes was less pronounced in all groups following lecithin supplementation.
      Lecithin supplementation of the diet did not elicit any pathological lesions and
      may be considered as a hepatocyte protector. This favourable effect of lecithin
      was most marked in the group of rats fed the fish oil.

PMID- 10905816
TI  - Morphometric study of the equine navicular bone: age-related changes and
      influence of exercise.
AB  - Navicular bones from the four limbs of 95 horses, classified in 9 categories,
      were studied. The effects of age on navicular bone morphometry and
      histomorphometry were estimated, after adjustment of the data to even out the
      effects of front and rear limbs, morphometrical type, sex, weight, and size. All
      the external measurements of the navicular bone decreased significantly with
      increasing age. From the histomorphometrical data, cortical bone volume decreased
      with age in most horses, whereas cancellous bone volume and, in particular, the
      marrow spaces increased. The increase in the cancellous bone volume could have
      resulted from tunnelling of the internal part of the cortex, which converted it
      progressively into a porous trabecular-like structure. Trabecular bone volume
      also decreased with age and the trabecular lattice changed dramatically to become
      disconnected in aged horses. These observations corresponded closely to those
      reported for ageing of the skeletal system in humans. However, in sporting
      horses, the navicular cortical bone volume increased with age and the cancellous
      bone volume decreased. Exercise appeared to have decreased bone resorption and
      increased bone formation at the endocortical junction. The cancellous bone
      architecture was also improved. in that the trabecular lattice and trabecular
      bone volume remained unchanged in aged sporting horses. Our findings confirmed
      that exercise may be good practice to prevent age-related bone loss.

PMID- 10905817
TI  - Beta-adrenoceptors in equine trachea and heart.
AB  - The density and subtype pattern of beta-adrenoceptors in equine tracheal
      epithelium, tracheal smooth muscle and heart from 6-9 horses were investigated by
      radioligand binding studies using the nonselective beta-adrenoceptor antagonist
      125I-cyanopindolol (ICYP). The specific binding of ICYP was 341 +/- 162 fmol/mg
      protein (mean +/- SD) for epithelium, 42 +/- 13 fmol/mg for smooth muscle and 124
      +/- 39 and 101+/- 19 fmol/mg for the cardiac atrium and ventricle, respectively.
      The Kd value of ICYP was 6.7 10.2 pmol/L. In competition studies, different
      concentrations of either the beta2-selective drug ICI 118551 or the beta1
      selective CGP 20712A competed with 25 pmol/L ICYP for the binding sites. The
      competition curves for tracheal smooth muscle and epithelium were monophasic with
      an approximate Kd value for ICI 118551 of 1 nmol/L and for CGP 20712A of 10000
      nmol/L. This corresponds to known Kd values for these substances binding to beta2
      adrenoceptors. beta2-Adrenoceptors were also found in the heart, most pronounced
      in the atrium, where the density was 29% +/- 6% (mean +/- SD) of the total
      receptor density. CGP 20712A and ICI 118551 bound to the dominating binding site
      of beta1-adrenoceptors in the heart with Kd values of approximately I nmol/L and
      100 nmol/L, respectively.

PMID- 10905819
TI  - Misdiagnoses of tuberculosis resulting from laboratory cross-contamination of
      Mycobacterium tuberculosis cultures--New Jersey, 1998.
AB  - A diagnosis of tuberculosis (TB) is rarely disputed if Mycobacterium tuberculosis
      is isolated from a clinical specimen; however, specimen contamination may occur
      (1-3). Identification of TB strain patterns through molecular typing or DNA
      fingerprinting is a recent advancement in TB laboratory techniques (3-7). CDC's
      National Tuberculosis Genotyping and Surveillance Network (NTGSN) performs DNA
      fingerprinting on TB isolates to determine the frequency of clustering among M.
      tuberculosis strains in project surveillance sites. In November 1998, NTGSN
      detected 11 isolates from previously reported TB cases among persons in New
      Jersey whose DNA fingerprints matched the avirulent laboratory M. tuberculosis
      control strain H37Ra. H37Ra does not cause active TB in humans, but it has been
      reported as a source of cross-contamination (8). In collaboration with the New
      Jersey Department of Health and Senior Services, CDC investigated H37Ra as a
      possible cause of TB disease and/or TB misdiagnoses caused by laboratory cross
      contamination in the 11 case-patients. This report describes findings from two of
      the 11 cases and summarizes the results of this investigation, which indicate
      that TB was misdiagnosed and demonstrate the value of DNA fingerprinting to
      identify occurrences of cross-contamination of patient specimens.

PMID- 10905818
TI  - The genetics of mortality and survival of broiler chicks infected as embryos by
      subgroup A Rous sarcoma virus.
AB  - A study using two high-performance broiler lines, a synthetic male line (SML) and
      a synthetic dam line (SDL), was undertaken to investigate the pattern of
      mortality due to induced liver tumours (LT) and the immune response to subgroup A
      virus inoculated via the chorioallantoic membrane (CAM) route. The distribution
      patterns of the four possible phenotypes were similar in both sire and dam lines.
      The occurrence of conversely associated phenotypes was about 30S, in both the
      lines. The percentages of CAM(+) LT(-) and CAM(-) LT(+) were 14.26%, and 14.46%
      in the dam line and 20.0% and 9.57% in the male line. The LT mortality was 30-50%
      in the birds with low pock counts, whereas it was 80-93% in the birds with high
      pock counts. The group specific antigen shedding status did not influence death
      due to LT. In birds in the high pock count group, 98% of deaths due to LT were
      completed by the sixth week, whereas in those in the low pock count group, death
      due to LT was spread over 24 weeks. The SDL birds survived better than SML birds
      in the high pock count groups. In both lines, about 20% of deaths occurred owing
      to non-specific causes. The average survival time after hatching before death
      from LT was 26 days, whereas that for non-specific death was 81 days.

PMID- 10905820
TI  - Cause-specific adult mortality: evidence from community-based surveillance-
      selected sites, Tanzania, 1992-1998.
AB  - Mortality data are a standard information resource to guide public health action.
      Because Tanzania did not have a representative mortality surveillance system, in
      1992 the Adult Morbidity and Mortality Project (AMMP) was established by the
      Muhimbili University College of Health Sciences, the Ministry of Health of
      Tanzania (MOH), and the University of Newcastle upon Tyne, United Kingdom. The
      purpose of the surveillance system is to provide cause-specific death rates among
      adults in three areas of Tanzania and to link community-based mortality
      surveillance to evidence-based planning for health care. This report describes
      the results of AMMP surveillance during 1992-1998, which indicated that human
      immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS)
      was the leading cause of death reported by decedents' relatives and caretakers
      for adults of both sexes in all study areas, and suggests that a range of other
      causes of death exist across the three surveillance sites.

PMID- 10905821
TI  - Prevalence of leisure-time and occupational physical activity among employed
      adults--United States, 1990.
AB  - Regular physical activity and high levels of physical fitness offer numerous
      health benefits, such as reduced risk for cardiovascular disease, diabetes,
      obesity, some cancers, and musculoskeletal conditions (1). National rates for
      participation in leisure-time physical activity are consistently low for women,
      older adults, persons with low educational attainment, and racial/ethnic
      minorities (2). Public health recommendations for promoting physical activity
      emphasize moderate-intensity activities, building on recommendations for vigorous
      exercise to improve fitness (3,4). To determine the prevalence of leisure-time
      and occupational physical activity, data were analyzed for employed adults aged >
      or = 18 years in the 1990 National Health Interview Survey (NHIS). This report
      summarizes the results of the survey, which indicate that approximately half of
      adults who reported no physical activity during leisure time also reported that
      they performed at least 1 hour per day of hard physical activity at work.

PMID- 10905822
TI  - Cyclic-AMP-dependent protein kinase (PKA) in testicular cells. Cell specific
      expression, differential regulation and targeting of subunits of PKA.
AB  - LH and FSH regulate via cyclic adenosine 3'5' cyclic monophosphate (cAMP) and
      cAMP-dependent protein kinase (PKA), steroid biosynthesis is Leydig and Sertoli
      cells, respectively. Cyclic AMP also regulates a number of different cellular
      processes such as cell growth and differentiation, ion channel conductivity,
      synaptic release of neurotransmitters, and gene transcription. The principle
      intracellular target for cAMP in mammalian cells is the PKA. The fact that this
      broad specificity protein kinase mediates a number of discrete physiological
      responses following cAMP engagement, has raised the question of how specificity
      is maintained in the cAMP/PKA system. Here we describe features of this signaling
      pathway that may contribute to explain how differential effects of cAMP may
      occur.

PMID- 10905823
TI  - [Proposal for a social class measure. Working Group of the Spanish Society of
      Epidemiology and the Spanish Society of Family and Community Medicine].

PMID- 10905824
TI  - [CT angiography of coronary vessels in coronary 3-vessel disease].

PMID- 10905825
TI  - A crush on the heart with CPR.

PMID- 10905826
TI  - Influence of non-bonded parameters on the quality of NMR structures: a new force
      field for NMR structure calculation.
AB  - The effects of different non-bonded parameters of force fields for NMR structure
      calculation on the quality of the resulting NMR solution structures were
      investigated using Interleukin 4 as a model system. NMR structure ensembles were
      calculated with an ab initio protocol using torsion angle dynamics. The
      calculations were repeated with five different non-bonded energy functions and
      parameters. The resulting ensembles were compared with the available X-ray
      structures, and their quality was assessed with common structure validation
      programs. In addition, the impact of torsion angle restraints and dihedral energy
      terms for the sidechains and the backbone was studied. The further improvement of
      the quality by refinement in explicit solvent was demonstrated. The optimal
      parameters, including those necessary for water refinement, are available in the
      new version of the PARALLHDG force field.

PMID- 10905827
TI  - StarDOM: from STAR format to XML.
AB  - StarDOM is a software package for the representation of STAR files as document
      object models and the conversion of STAR files into XML. This allows interactive
      navigation by using the Document Object Model representation of the data as well
      as easy access by XML query languages. As an example application, the entire
      BioMagResBank has been transformed into XML format. Using an XML query language,
      statistical queries on the collected NMR data sets can be constructed with very
      little effort. The BioMagResBank/XML data and the software can be obtained at
      http://www.nmr.embl-heidelberg.de/nmr/StarDOM linge@embl-heidelberg.de

PMID- 10905828
TI  - Length of penicillin treatment of streptococcal infections. Antibiotics should
      not be used for self limiting illnesses.

PMID- 10905829
TI  - Length of penicillin treatment of streptococcal infections. Is seven days of
      treatment as effective as 10 days.

PMID- 10905830
TI  - Length of penicillin treatment of streptococcal infections. The data do not
      support the conclusions.

PMID- 10905831
TI  - Length of penicillin treatment of streptococcal infections. Care must be taken
      when extrapolating data.

PMID- 10905832
TI  - Length of penicillin treatment of streptococcal infections. Life tables should be
      used with caution.

PMID- 10905833
TI  - Treating children with sleep disorders. Children with breathing difficulties are
      being overlooked.

PMID- 10905834
TI  - Treating children with sleep disorders. Night waking is natural behaviour.

PMID- 10905835
TI  - Treating children with sleep disorders. Early intervention increases sleep times
      in young babies.

PMID- 10905836
TI  - Treating children with sleep disorders. Treatment of child sleeping problems and
      the quality of trials are important.

PMID- 10905837
TI  - Recent advances in intensive care. Percutaneous tracheostomy may not be more
      effective than open technique.

PMID- 10905838
TI  - Recent advances in intensive care. More still needs to be known about
      immunonutrition.

PMID- 10905839
TI  - Genetic factors and osteoporotic fractures in elderly people. Twin data support
      genetic contribution to risk of fracture.

PMID- 10905840
TI  - Genetic factors and osteoporotic fractures in elderly people. Study supports
      possibility of differences in development of osteoporotic fractures between
      sexes.

PMID- 10905841
TI  - Improving the debate on cannabis. Consider public welfare, not just public
      health.

PMID- 10905842
TI  - Improving the debate on cannabis. Let's find out whether cannabis has therapeutic
      value.

PMID- 10905843
TI  - Improving the debate on cannabis. Social context should be added to domains being
      considered.

PMID- 10905844
TI  - Improving the debate on cannabis. The effects of cannabis on driving are
      difficult to evaluate.

PMID- 10905845
TI  - Emergency admissions in Stockport were exaggerated.

PMID- 10905846
TI  - Number of embryos allowed in fertility treatment should be flexible.

PMID- 10905847
TI  - [An ecological approach to the life experience of adolescents with cleft lip and
      palate].

PMID- 10905848
TI  - Information point: coefficient of determination, R2.

PMID- 10905849
TI  - Information point Mokken Scale Analysis.

PMID- 10905850
TI  - Breaking down barriers, building bridges.

PMID- 10905851
TI  - [Modern pharmacotherapy of glaucomas].

PMID- 10905853
TI  - [Clinical sequelae of the Chernobyl disaster. From the materials of 7th
      International scientific-practical conference "Man's Ecology in Post Chernobyl
      era" held Sept. 27-29, 1999 in Minsk].

PMID- 10905852
TI  - Cytogenetic findings in a case of brown tumor associated with
      hyperparathyroidism.

PMID- 10905854
TI  - Modern electroencephalography: its role in epilepsy management.

PMID- 10905855
TI  - Suporting the cost-effectiveness of a thyroid testing algorithm.

PMID- 10905856
TI  - The mechanism of histamine secretion from gastric enterochromaffin-like cells.

PMID- 10905857
TI  - Effects of arginine vasopressin on water space in astrocytes and in whole brain.

PMID- 10905858
TI  - Synthesis and preliminary assessments of ethyl-terminated perfluoroalkyl nonionic
      surfactants derived from tris(hydroxymethyl)acrylamidomethane.
AB  - We describe the synthesis and preliminary physicochemical and biological
      assessments of a new class of nonionic hybrid hydrofluoro amphiphiles derived
      from tris(hydroxymethyl)aminomethane (THAM). The synthesis of the hydrophobic
      tail of these amphiphiles is based on the preparation of an asymmetrical
      hydrofluorocarbon derivative containing an ethyl segment, a fluorocarbon core,
      and an ethyl thiol moiety. This molecule led to either THAM galactosylated
      monoadducts or telomers. These amphiphiles exhibit neither detergency toward cell
      membranes nor membrane protein denaturation.

PMID- 10905859
TI  - A new cyclohexadecane derivative from Trixis vauthieri DC (Asteraceae).
AB  - The dichloromethane-methanol extract from the fresh leaves of Trixis vauthieri DC
      (Asteraceae) afforded trixol, a new cyclohexadecane derivative. The structural
      elucidation of this new compound, with a novel skeleton, was based on NMR studies
      of the natural product nd its derivatives.

PMID- 10905860
TI  - Studies toward the biomimetic synthesis of tropolone natural products via a
      hetero Diels-Alder reaction.
AB  - Analogues of the tropolone natural products pycnidione and epolone B were
      synthesized via a hetero Diels-Alder reaction of benzotropolone 10 with humulene.
      The quinone methide benzotropolone 13 was generated in situ by thermalisation of
      benzotropolone 10. Benzotropolone 10 was derived from phthalic acid via carbonyl
      ylide 8a followed by an intramolecular 1,3-dipolar cycloaddition and subsequent
      acid-catalyzed ring opening.

PMID- 10905861
TI  - A biomimetic synthesis of lucidene.
AB  - Lucidene has been shown to be derived from alpha-humulene and o-benzoquinone
      methide generated under thermal conditions.

PMID- 10905862
TI  - Synthesis of (--)-lasubine(I) via a planar chiral [(eta6-arene)Cr(CO)3] complex.
AB  - Key steps of the synthesis of the Lythracaea alkaloid (--)-lasubine(I) are the
      formation of an enantiopure planar chiral arylaldehyde tricarbonylchromium
      complex and highly diastereoselective aza-Diels-Alder cycloaddition and
      intramolecular radical cyclization reactions to afford a quinolizidinone
      intermediate. Ketone reduction, desilylation, and decomplexation yield the
      enantiomerically pure product.

PMID- 10905863
TI  - Total synthesis of a new cytotoxic acetogenin, jimenezin, and the revised
      structure.
AB  - The first total synthesis of jimenezin was achieved by using carbohydrates as
      chiral building blocks, thus revising the proposed structure 1 to 2. The key
      steps in this synthesis include an efficient construction of the THP-THF
      fragments 3 and 16 through a stereoselective condensation between the pyranyl
      aldehyde 5 and the acetylene derivative 6, and a palladium-catalyzed coupling
      reaction of 3 or 16 with a terminal butenolide 4.

PMID- 10905864
TI  - Selective epimerization of rapamycin via a retroaldol/aldol mechanism mediated by
      titanium tetraisopropoxide.
AB  - We describe the efficient and selective epimerization of the immunosuppressant
      rapamycin to 28-epirapamycin under mild conditions. The mechanism of
      epimerization involves an equilibrium of the four C28/C29 diastereomers through a
      two-step retroaldol/aldol (macrocycle ring-opening/ring-closing) sequence. This
      retroaldol/aldol equilibration is not restricted to rapamycin but is also
      applicable to acyclic beta-hydroxyketones. A potentially useful extension of the
      method--the use of beta-hydroxyketones as enolate synthons for effecting inter-
      or intramolecular aldol reactions under neutral conditions--is demonstrated.

PMID- 10905865
TI  - Effect of the alpha-methyl substituent on chemoselectivity in esterase-catalyzed
      hydrolysis of S-acetyl sulfanylalkanoates.
AB  - The isomeric compounds 1 and 3, which differ only in the position of a methyl
      substituent, give opposite chemoselectivities in an esterase-catalyzed hydrolysis
      reaction. The esterase was chemoselective for the oxoester in 1, but for the
      thiol ester group in 3. A high enantioselectivity was observed for both 1 and 3.

PMID- 10905866
TI  - Synthesis and use of glycosyl phosphates as glycosyl donors.
AB  - Differentially protected glycosyl phosphates prepared by a straightforward
      synthesis from glycal precursors are used as powerful glycosyl donors. Activation
      of beta-glycosyl phosphates by TMSOTf at -78 degrees C achieves the selective
      formation of beta-glycosidic linkages in excellent yields with complete
      stereoselectivity. Reaction with thiols results in the conversion of glycosyl
      phosphates into thioglycosides in nearly quantitative yield. An orthogonal
      coupling strategy using glycosyl phosphate donors and thioethyl glycoside
      acceptors allows for the rapid synthesis of a trisaccharide.

PMID- 10905867
TI  - Semisynthesis of abrusoside A methyl ester.
AB  - Abrusoside A methyl ester was prepared from abrusogenin through methylation
      (CH2N2) and a subsequent coupling reaction with 1-chloro-2,3,4,6-tetra-O
      acethylglucopyranose in the presence of AgOTf and TMU in CH2Cl2, followed by
      deacetylation using K2CO3 in MeOH-H2O.

PMID- 10905868
TI  - Catalytic asymmetric synthesis of diarylacetate and 4,4-diarylbutanoates. A
      formal asymmetric synthesis of (+)-sertraline.

PMID- 10905869
TI  - Efficient synthesis of 40- and 48-membered tetraether macrocyclic
      bisphosphocholines.
AB  - An efficient route toward the synthesis of unsaturated (bis-diacetylenic) and
      saturated 40- and 48-membered macrocyclic biphosphocholines has been developed
      using 2-phenyl-5-hydroxy-1,3-dioxane as a common glycerol synthon. Ring closure
      was accomplished using either high-dilution Glaser oxidation of
      [(Cy3P)2RU==CHPh]Cl2-catalyzed olefin metathesis conditions. Deprotection of
      benzyl ethers using trimethylsilyl iodide (TMS-I) in the presence of diacetylenic
      moieties has also been demonstrated for the first time.

PMID- 10905870
TI  - Synthesis of beta-D-Galf-(1-3)-D-GlcNAc by the trichloroacetamidate method and of
      beta-D-Galf-(1-6)-D-GlcNAc by SnCl4-promoted glycosylation.
AB  - In a continuation of our studies on the characterization of the glycoproteins of
      T. cruzi new galactofuranosyl disaccharides were synthesized. Beta-D-Galf-(1-3)-D
      GlcNAc was prepared by employing the trichloroacetamidate procedure for the
      glycosylation step. The mild conditions of this reaction are appropriate for
      condensation of 2,3,5,6-tetra-O-benzoyl-beta-D-galactofuranosyl
      trichloroacetamidate with acid-labile benzyl 2-acetamido-4,6-O-benzylidene-2
      deoxy-alpha-D-glucopyranoside. On the other hand, tin(IV) chloride promoted
      condensation of benzyl 2-acetamido-3-O-benzoyl-2-deoxy-alpha-D-glucopyranoside
      with penta-O-benzoyl-alpha-beta-D-galactofuranose gave the derivative of beta-D
      Galf-(1-6)-D-GlcNAc in 78% yield.

PMID- 10905871
TI  - Arylpropane-1,3-diols in lignins from normal and CAD-deficient pines.
AB  - Significant quantities of arylopropane-1,3-diols have been identified in lignins
      isolated from a CAD-deficient pine mutant; smaller amounts are also present in
      lignins from normal pine. They arise from dihydroconiferyl alcohol via the action
      of peroxidases which are responsible for the radical generation steps of
      lignification. The structures in the complex lignin polymers are proven using 2D
      and 3D NMR of isolated lignin fractions.

PMID- 10905872
TI  - Simple and rapid visual sensing of saccharides.
AB  - Solutions of compound 1 exhibit dramatic, characteristic color changes in
      response to sugar analytes. Structurally related saccharides including glucose
      phosphates and amino and carboxylic acid sugars can be readily distinguished by
      visual inspection. These findings should promote the design of unique color
      sensory materials based on readily available, functional macrocyclic hosts.

PMID- 10905873
TI  - A concise total synthesis of (+/-)-bakkenolide A by means of an intramolecular
      Diels-Alder reaction.
AB  - (+/-)-Bakkenolide A was prepared in five steps from ethyl 4-benzyloxyacetoacetate
      by sequential alkylations with tiglyl bromide nd cis-5-bromo-1,3-pentadiene,
      followed by an intramolecular Diels-Alder reaction as the key step. The known 7
      epibakkenolide A and novel 10-epi- and 7,10-diepibakkenolide A stereoisomers were
      obtained as minor byproducts.

PMID- 10905874
TI  - [Spontaneous abdominal hematoma during jogging under acetylsalicylic acid
      therapy].

PMID- 10905876
TI  - [Cases of plagiarism in "Ginekologia Polska"].

PMID- 10905875
TI  - Co-ordinating editor's comments on the letter to the editors by A. Herxheimer.

PMID- 10905877
TI  - Clinical utility of early viral load quantification.

PMID- 10905878
TI  - Spur cell anemia explains the iron overload in advanced cirrhosis (C282Y
      negative)

PMID- 10905879
TI  - Neurobiology of exaggerated heart oscillations during two meditative techniques.

PMID- 10905880
TI  - Behcet's disease and HCV infection.

PMID- 10905881
TI  - Basal cell carcinoma of the nail bed in a Korean woman.

PMID- 10905882
TI  - Should hysteroscopy be a part of the basic infertility workup?

PMID- 10905883
TI  - 1999 JCO Orthodontic Practice Study. Part 2 Practice success.

PMID- 10905884
TI  - Lymphatic and haematopoietic cancer mortality.

PMID- 10905885
TI  - Vasculitic neuropathy in chronic graft-versus-host disease (GVHD)

PMID- 10905887
TI  - Know before you mow: a review of lawn mower injuries in children, 1990-1998.

PMID- 10905886
TI  - The chronic disease of childhood obesity: the sleeping giant has awakened.

PMID- 10905888
TI  - Human implantation: recent advances and clinical aspects. Proceedings of and
      international workshop. Valencia, Spain, 22-23 March 1999.

PMID- 10905889
TI  - Phosphorylase kinase deficient liver glycogenosis: progression to cirrhosis in
      infancy associated with PHKG2 mutations (H144Y and L225R)

PMID- 10905890
TI  - Familial Wilms tumour resulting from WT1 mutation: intronic polymorphism causing
      artefactual constitutional homozygosity.

PMID- 10905891
TI  - Silver-Russell syndrome and ring chromosome 7.

PMID- 10905892
TI  - Variants of STAT6 (signal transducer and activator of transcription 6) in atopic
      asthma.

PMID- 10905893
TI  - No linkage or association of the IL-4Ralpha gene Q576R mutation with atopic
      asthma in Italian families.

PMID- 10905894
TI  - Importance of the autosomal recessive retinitis pigmentosa locus on 1q31-q32.1
      (RP12) and mutation analysis of the candidate gene RGS16 (RGS-r)

PMID- 10905895
TI  - Incidence and molecular mechanism of aberrant splicing owing to a G-->C splice
      acceptor site mutation causing Smith-Lemli-Opitz syndrome.

PMID- 10905896
TI  - Clinical and molecular cytogenetic studies of a large de novo interstitial
      deletion 16q11.2-16q21 including the putative transcription factor gene SALL1.

PMID- 10905898
TI  - Anticipation in progressive diaphyseal dysplasia.

PMID- 10905897
TI  - Oculocutaneous albinism type 2 with a P gene missense mutation in a patient with
      Angelman syndrome.

PMID- 10905899
TI  - Hereditary neuropathy with liability to pressure palsies: two cases with a
      reciprocal translocation t(16;17)(q12;11.2) interrupting the PMP22 gene.

PMID- 10905900
TI  - From the Centers for Disease Control and Prevention. Prevalence of cigarette
      smoking among secondary school students--Budapest, Hungary, 1995 and 1999.

PMID- 10905901
TI  - From the Centers for Disease Control and Prevention. Misdiagnoses of tuberculosis
      resulting from laboratory cross-contamination of Mycobacterium tuberculosis
      cultures--New Jersey, 1998.

PMID- 10905902
TI  - From the Centers for Disease Control and Prevention. Costs of smoking among
      active duty US Air Force personnel--United States, 1997.

PMID- 10905903
TI  - From the Centers for Disease Control and Prevention. Cause-specific adult
      mortality: evidence from community-based surveillance--selected sites, Tanzania,
      1992-1998.

PMID- 10905904
TI  - JAMA patient page. Treating tobacco dependence.

PMID- 10905905
TI  - JAMA patient page. Caring for loved ones who are mentally impaired.

PMID- 10905906
TI  - From the Food and Drug Administration.

PMID- 10905907
TI  - From the Centers of Disease Control and Prevention. Heat-related illnesses,
      deaths, and risk factors--Cincinnati and Dayton, Ohio, 1999, and United States,
      1979-1997.

PMID- 10905908
TI  - From the Centers of Disease Control and Prevention. Prevalence of selected
      cardiovascular disease risk factors among American Indians and Alaska Natives-
      United States, 1997.

PMID- 10905909
TI  - Molecular detection of lymphoid-specific genetic markers in chronic myelogenous
      leukemia in chronic phase.

PMID- 10905910
TI  - Myeloid/natural killer (NK) cell precursor acute leukemia seems not rare among
      acute myeloid leukemia of M0 subtype (AML-M0)

PMID- 10905911
TI  - Change in occurrence of paracetamol overdose in UK after introduction of blister
      packs.

PMID- 10905912
TI  - Re: Career choices at the end of the pre-registration year of doctors who
      qualified in the United Kingdom in 1996.

PMID- 10905913
TI  - The influence of examination forms.

PMID- 10905914
TI  - Professional modelling: a questionnaire study of junior doctors' attitudes to
      aspects of experiential learning on the hospital working round.

PMID- 10905916
TI  - Students as customers.

PMID- 10905915
TI  - Who should manage head and neck pathology?

PMID- 10905917
TI  - Junior doctor training.

PMID- 10905918
TI  - Views of junior doctors about their work.

PMID- 10905919
TI  - Research in medical education: the law of diminishing non-returns?

PMID- 10905920
TI  - Task-based learning.

PMID- 10905921
TI  - Learning about being well--not just about being ill.

PMID- 10905922
TI  - Contraceptive requirements for clinical research.
AB  - OBJECTIVE: To survey the type and frequency of use of contraceptive requirements
      for entry into clinical trials. METHODS: We reviewed 410 protocols submitted
      between January 1994 and January 1997 to one Institutional Review Board. RESULTS:
      Contraception or sterility for women was required in 171 (41.7%) protocols
      without explanation and 146 (35.6%) based on study drug. Eight and one half
      percent hd no exclusions. Signature certification of contraceptive use was
      required in 138 protocols; 230 required certification of understanding
      requirements; and 101 required two signatures. Signature certification
      documenting no pregnancy at enrollment was required in 234 protocols. There were
      no requirements for signatures from male subjects. Celibacy or sexual orientation
      were not recognized as reasons for waiver from signature requirements.
      CONCLUSION: The broad application of contraceptive requirements potentially
      creates disproportionate burdens and access by gender to participation in
      clinical research. Careful elucidation of methods, timing, and the consent
      process in order to avoid potential fetal risk and encourage inclusion of
      hormonally intact women will improve research and access.

PMID- 10905923
TI  - Hemostatic ligature for operative laparoscopy.
AB  - BACKGROUND: We introduce a safe and convenient method for ligature of vascular
      pedicles at laparoscopic surgery in which one laparoscopic and two auxillary
      ports are used. TECHNIQUE: The first two-turn wrap around the loop is made
      extracorporeally with the hand and is locked by an intracorporeal tie with
      manipulation of the target tissue. Knot typing is finished with the second and
      third nontension tie of one-turn throws. EXPERIENCE: We have used this method for
      laparoscopic surgery for more than 2.5 years and have not observed a failure or
      late hemorrhage. CONCLUSION: Two-turn throw incomplete loop ligature is a useful
      and convenient technique for hemostasis in three-port pelviscopic operations.

PMID- 10905924
TI  - Laparoscopic vaginal delivery: report of a case, literature review, and
      discussion.

PMID- 10905926
TI  - Veterinary parasitology: recent developments in immunology, epidemiology and
      control. Proceedings of a meeting.

PMID- 10905925
TI  - The ethics of acute pain studies in the 21st Century.

PMID- 10905927
TI  - Comments on "Effectiveness of protons and argon ions in initiating lipid
      peroxidation in low-density lipoproteins" by Ziegler et al. (Radiat. Res. 150,
      483-487, 1998)

PMID- 10905928
TI  - Comparison of parametrization methods of the collimator scatter correction factor
      for open rectangular fields of 6-25 MV photon beams.

PMID- 10905929
TI  - Volatile constituents of Cunila polyantha (Lamiaceae) from Costa Rica. A rich
      source of menthone.
AB  - The constituents of the volatile oil of Cunila polyantha from Dota, Costa Rica,
      were investigated using coupled gas chromatography-mass spectrometry (GC-MS)
      analyses. Menthone (63%), pulegone (14%), beta-caryophyllene (4.5%) and 3-octanyl
      acetate (3%) were found to be the major constituents of the volatile oil.

PMID- 10905930
TI  - Management of chronic disabling low back pain with 360 degrees fusion.

PMID- 10905931
TI  - Mechanism and role of antidiuretic hormone.

PMID- 10905932
TI  - A gunshot wound to the head--the case of Abraham Lincoln.

PMID- 10905933
TI  - Re: What are those soldiers doing? They're holding the horses!

PMID- 10905934
TI  - Re: What are those soldiers doing? They're holding the horses!

PMID- 10905935
TI  - [Heart failure].

PMID- 10905936
TI  - [Unrest in the Netherlands due to the threat of highly pathogenic avian influenza
      from Italy].

PMID- 10905937
TI  - [Cobalt-/vitamin B12-deficiency in beef cattle: a short review].

PMID- 10905938
TI  - [The harbor seal (Phoca vitulina) in the last century].

PMID- 10905939
TI  - [Foundation for Animal Aid of Venezuela in a scandal].

PMID- 10905940
TI  - [Heck cattle in the Oostvaardersplassen. Risks of a risk communication].

PMID- 10905941
TI  - [Reaction to 'salmonella in eggs'].

PMID- 10905943
TI  - [Future of avian influenza. State of business and measures].

PMID- 10905942
TI  - [Predecessors: veterinarians from earlier times (38). Karl Heinrich Hertwig (1798
      1881)].

PMID- 10905944
TI  - [Fight against infectious bovine rhinotracheitis and those worn down remaining in
      the spotlight. Lack of clarity makes the question drag on].

PMID- 10905946
TI  - [The rise of the Clinic for Small Domestic Animals].

PMID- 10905945
TI  - [Veterinary drug profile of Equest].

PMID- 10905947
TI  - [Acts in clients with owner unknown: dilemmas].

PMID- 10905948
TI  - [Prof. Vasil Mollov, his leading role in Bulgarian internal medicine, 1875-1938].

PMID- 10905949
TI  - Efficient vaccination strategy against typhoid fever.

PMID- 10905951
TI  - [The centenary of the birth of Salar Agarafievich Imamaliev].

PMID- 10905950
TI  - [The history of uncovering the feeding route of infection by the tick-borne
      encephalitis virus].

PMID- 10905952
TI  - [The 90th anniversary of the Rostov Scientific Research Institute of Microbiology
      and Parasitology].

PMID- 10905953
TI  - [The history of the origin and development of the Tomsk Scientific Research
      Institute of Vaccines and Sera].

PMID- 10905955
TI  - [14th Congress of the European Association of Urology. Stockholm, April 1999].

PMID- 10905954
TI  - [The 75th anniversary of the Zhurnal mikrobiologii, epidemiologii i
      immunobiologii].

PMID- 10905956
TI  - Artificial intelligence and its relevance in the craniofacial context.

PMID- 10905957
TI  - Psychiatrists' attitudes toward dissociative disorders diagnoses.

PMID- 10905958
TI  - Psychiatrists' attitudes toward dissociative disorders diagnoses.

PMID- 10905960
TI  - Society of Analytical Chemistry Conference. Dublin City University, Republic of
      Ireland, 25-30 July 1999. Proceedings.

PMID- 10905959
TI  - Psychiatrists' attitudes toward dissociative disorders diagnoses.

PMID- 10905961
TI  - Silica and lung cancer: hazard or risk.

PMID- 10905962
TI  - Fourteenth Convocation, Royal Australasian College of Dental Surgeons. Adelaide,
      Australia, October 1998. Papers.

PMID- 10905963
TI  - Caring for marginalised people. All doctors should be taught and tested.

PMID- 10905964
TI  - Migratory birds and spread of West Nile virus in the Western Hemisphere.
AB  - West Nile virus, an Old World flavivirus related to St. Louis encephalitis virus,
      was first recorded in the New World during August 1999 in the borough of Queens,
      New York City. Through October 1999, 62 patients, 7 of whom died, had confirmed
      infections with the virus. Ornithophilic mosquitoes are the principal vectors of
      West Nile virus in the Old World, and birds of several species, chiefly migrants,
      appear to be the major introductory or amplifying hosts. If transovarial
      transmission or survival in overwintering mosquitoes were the principal means for
      its persistence, West Nile virus might not become established in the New World
      because of aggressive mosquito suppression campaigns conducted in the New York
      area. However, the pattern of outbreaks in southern Europe suggests that viremic
      migratory birds may also contribute to movement of the virus. If so, West Nile
      virus has the potential to cause outbreaks throughout both temperate and tropical
      regions of the Western Hemisphere.

PMID- 10905965
TI  - Male-killing bacteria in insects: mechanisms, incidence, and implications.
AB  - Bacteria that are vertically transmitted through female hosts and kill male hosts
      that inherit them were first recorded in insects during the 1950s. Recent studies
      have shown these "male-killers" to be diverse and have led to a reappraisal of
      the biology of many groups of bacteria. Rickettsia, for instance, have been
      regarded as human pathogens transmitted by arthropods. The finding of a male
      killing Rickettsia obligately associated with an insect suggests that the genus'
      members may be primarily associated with arthropods and are only sometimes
      pathogens of vertebrates. We examined both how killing of male hosts affects the
      dynamics of inherited bacteria and how male-killing bacteria affect their host
      populations. Finally, we assessed the potential use of these microorganisms in
      the control of insect populations.

PMID- 10905966
TI  - Communicating the threat of emerging infections to the public.
AB  - Communication theory and techniques, aided by the electronic revolution, provide
      new opportunities and challenges for the effective transfer of laboratory,
      epidemiologic, surveillance, and other public health data to the public who funds
      them. We review the applicability of communication theory, particularly the
      audience-source-message-channel meta-model, to emerging infectious disease
      issues. Emergence of new infectious organisms, microbial resistance to
      therapeutic drugs, and increased emphasis on prevention have expanded the role of
      communication as a vital component of public health practice. In the absence of
      cure, as in AIDS and many other public health problems, an effectively crafted
      and disseminated prevention message is the key control measure. Applying
      communication theory to disease prevention messages can increase the
      effectiveness of the messages and improve public health.

PMID- 10905967
TI  - Reemergence of pertussis in the highly vaccinated population of the Netherlands:
      observations on surveillance data.
AB  - We analyzed pertussis reporting, death, hospitalization, and serodiagnostic data
      from 1976 to 1998 to help explain the cause of the 1996 pertussis outbreak in the
      Netherlands. The unexpected outbreak was detected by an increase in pertussis
      reporting and by other surveillance methods. In 1996, according to reporting and
      serologic data, the increase in pertussis incidence among (mostly unvaccinated)
      children less than 1 year of age was similar to the increase in hospital
      admissions. Among older (mostly vaccinated) persons, the increase in hospital
      admissions was relatively small. The increase in pertussis incidence was higher
      among vaccinated than among unvaccinated persons of all ages. This resulted in
      lower estimates of vaccine effectiveness. The proportion of pertussis infections
      resulting in recognizable symptoms may have increased among vaccinated persons
      because of a mismatch of the vaccine strain and circulating Bordetella pertussis
      strains. The small immunogenicity profile of the Dutch vaccine may have resulted
      in greater vulnerability to antigenic changes in B. pertussis.

PMID- 10905968
TI  - Seroprevalence of West Nile, Rift Valley, and sandfly arboviruses in Hashimiah,
      Jordan.
AB  - We conducted a serosurvey among patients of a health center in Hashimiah, a
      Jordanian town of 30,000 inhabitants located near a wastewater treatment plant
      and its effluent channel. Serum samples from 261 patients >/=5 years of age were
      assessed for immunoglobulin G (IgG) and IgM antibodies against West Nile, sandfly
      Sicilian, sandfly Naples, and Rift Valley viruses; the seroprevalence of IgG
      antibodies was 8%, 47%, 30%, and 0%, respectively. Female participants were more
      likely to have been infected than male. Persons living within 2 km of the
      treatment plant were more likely to have been infected with West Nile (p=0.016)
      and sandfly Sicilian (p=0.010) viruses. Raising domestic animals within the house
      was a risk factor for sandfly Sicilian (p=0.003) but not for sandfly Naples virus
      (p=0.148). All serum samples were negative for IgM antibodies against the tested
      viruses. Our study is the first documentation of West Nile and sandfly viruses in
      Jordan and calls attention to the possible health hazards of living close to
      wastewater treatment plants and their effluent channels.

PMID- 10905969
TI  - The role of pathology in an investigation of an outbreak of West Nile
      encephalitis in New York, 1999.
AB  - An outbreak of encephalitis occurred in New York City in late August 1999, the
      first caused by West Nile virus in North America. Histopathologic and
      immunopathologic examinations performed on human autopsy materials helped guide
      subsequent laboratory and epidemiologic investigations that led to identification
      of the etiologic agent.

PMID- 10905970
TI  - Isolation of two strains of West Nile virus during an outbreak in southern
      Russia, 1999.
AB  - From July to September 1999, a widespread outbreak of meningoencephalitis
      associated with West Nile virus (Flavivirus, Flaviviridae) occurred in southern
      Russia, with hundreds of cases and dozens of deaths. Two strains of West Nile
      virus isolated from patient serum and brain-tissue samples reacted in
      hemagglutination-inhibition and neutralization tests with patients' convalescent
      phase sera and immune ascites fluid from other strains of West Nile virus.

PMID- 10905971
TI  - Subacute sclerosing panencephalitis, a measles complication, in an
      internationally adopted child.
AB  - A healthy 13-year-old boy who had spent the first 4.5 years of his life in an
      orphanage in Thailand before adoption by an American couple became ill with
      subacute sclerosing panencephalitis and died several months later. The boy had
      most likely contracted wild-type measles in Thailand. Measles complications are a
      risk in international adoptions.

PMID- 10905972
TI  - Bacteremia and endocarditis caused by a Gordonia species in a patient with a
      central venous catheter.
AB  - We report the first case of endocarditis caused by a Gordonia species genetically
      related to G. sputi but exhibiting some atypical biochemical features in a 31
      year-old woman with a central venous catheter. This unusual pathogen may be a new
      cause of opportunistic infections in patients with severe underlying diseases.

PMID- 10905973
TI  - Sin nombre virus in deer mice captured inside homes, southwestern Montana.
AB  - From 1996 through 1999, 35 deer mice (Peromyscus maniculatus) were captured in 25
      urban and suburban homes in southwestern Montana. Mice were captured throughout
      the year except for January; seven mice (20%) from seven (28%) of the homes were
      seropositive for Sin Nombre virus. The infected mice were mostly adult males
      captured in the spring and fall.

PMID- 10905975
TI  - Antibiotic resistance in Escherichia coli from Nigerian students, 1986 1998.
AB  - We tested 758 fecal Escherichia coli isolates, recovered from Nigerian students
      in 1986, 1988, 1990, 1994, and 1998, for susceptibility to seven antimicrobial
      drugs. The prevalences of strains resistant to tetracycline, ampicillin,
      chloramphenicol, and streptomycin were 9% to 35% in 1986 and 56% to 100% in 1998.
      These findings demonstrate that resistance gene reservoirs are increasing in
      healthy persons.

PMID- 10905974
TI  - Evidence of Rickettsia helvetica infection in humans, eastern France.
AB  - A 37-year-old man living in eastern France seroconverted to Rickettsia helvetica
      in August 1997, 4 weeks after the onset of an unexplained febrile illness.
      Results of a serosurvey of forest workers from the area where the patient lived
      showed a 9.2% seroprevalence against R. helvetica. This organism may pose a
      threat for populations exposed to Ixodes ricinus ticks.

PMID- 10905976
TI  - Ehrlichia chaffeensis antibodies in white-tailed deer, Iowa, 1994 and 1996.
AB  - Surveillance of 2,277 white-tailed deer for antibodies against Ehrlichia
      chaffeensis in Iowa showed seropositivity rates of 12.5% in 1994 and 13.9% in
      1996. From 1994 to 1996, the estimated number of seropositive deer increased to
      54,701 (28%). The increasing deer population and expanding tick distribution may
      increase risk for human monocytic ehrlichiosis.

PMID- 10905977
TI  - Antimicrobial resistance in Salmonella enteritidis, southern Italy, 1990-1998.
AB  - During 1990 to 1998, we identified multidrug-resistant isolates of Salmonella
      Enteritidis in southern Italy. Plasmids containing class I integrons and
      codifying for synthesis of extended- spectrum beta-lactamases were detected.
      Active surveillance for resistance to antimicrobial agents is needed to guard
      against the possible spread of resistant clones.

PMID- 10905978
TI  - Lyme disease surveillance in England and Wales, 1986 1998.
AB  - Improved surveillance indicates that Lyme borreliosis, an emerging zoonosis in
      the United Kingdom, has increased from 0.06/100,000 during 1986-1992 to
      0.32/100,000 since 1996. Case reports peaked in the third quarter of each year.
      Several high-incidence localities were identified. Erythema migrans was reported
      in 41% of patients; arthritis in 4%; musculoskeletal symptoms in 18%; and
      neuroborreliosis in 15%.

PMID- 10905979
TI  - Borrelia burgdorferi and the causative agent of human granulocytic ehrlichiosis
      in deer ticks, Delaware.
AB  - During the 1998 hunting season in Delaware, 1,480 ticks were collected from 252
      white- tailed deer; 98% were Ixodes scapularis, a significant increase from the
      85% reported in 1988. Ticks were tested for Borrelia burgdorferi and the
      causative agent of human granulocytic ehrlichiosis. Infection rates remained
      stable in New Castle and Kent counties, but increased from <1% to 8% in sussex
      county.

PMID- 10905980
TI  - Primary care surveillance for acute bloody diarrhea, Wales.
AB  - A sentinel group of primary-care physicians in Wales actively reported cases of
      acute bloody diarrhea from February 1997 through December 1998. The estimated
      annual rate was 18 cases per 100,000 population. Most (80%) cases were due to
      Campylobacter or Salmonella; however, 18% were undiagnosed.

PMID- 10905981
TI  - Epidemic spread of adenovirus type 4-associated acute respiratory disease between
      U.S. Army installations.
AB  - A large outbreak of adenovirus type 4-associated acute respiratory disease (ARD)
      occurred at Fort Jackson, South Carolina, in 1997. A laboratory-based ARD
      surveillance program was initiated at Fort Gordon, Georgia, where advanced
      individual training was heavily populated with Fort Jackson soldiers. Adenovirus
      type 4 was isolated from 50% of 147 trainees hospitalized with ARD. Most (88%)
      introduced cases were in trainees from Fort Jackson.

PMID- 10905983
TI  - Dengue epidemic in southern Vietnam, 1998.
AB  - A widespread epidemic of dengue hemorrhagic fever (DHF) occurred in southern
      Vietnam in 1998, with 438.98 cases/100,000 population and 342 deaths. The number
      of DHF cases and deaths per 100,000 population increased 152.4% and 151.8%,
      respectively, over a 1997 epidemic. Dengue viruses were isolated from 143 patient
      blood samples; DEN-3 virus was identified as the predominant serotype, although a
      resurgence of DEN-4 was noted.

PMID- 10905982
TI  - Drug-resistant Salmonella enterica serotype paratyphi A in India.
AB  - The incidence of enteric fever caused by Salmonella enterica serotype Paratyphi A
      has been increasing in India since 1996. In 1998, the incidence of enteric fever
      caused by drug- resistant S. Paratyphi A abruptly increased in the New Delhi
      region. In the first 6 months of 1999, 32% of isolates were resistant to both
      chloramphenicol and cotrimoxazole and another 13% were resistant to more than two
      antibiotics.

PMID- 10905985
TI  - Gnathostomosis in fish from Tres Palos Lagoon, Guerrero, Mexico.

PMID- 10905984
TI  - Neisseria meningitidis serogroup W135 isolates associated with the ET-37 complex.

PMID- 10905986
TI  - First report of human granulocytic ehrlichiosis from southern Europe (Spain).

PMID- 10905987
TI  - Phylogenetic analysis of the Chinese Rickettsia isolate BJ-90.

PMID- 10905988
TI  - Specimen collection for electron microscopy.

PMID- 10905989
TI  - Antimicrobial resistance.

PMID- 10905990
TI  - Changes in antimicrobial resistance in Salmonella enterica serovar typhimurium.

PMID- 10905992
TI  - Malaria and global warming in perspective?

PMID- 10905995
TI  - Kinetic study of acamprosate absorption in rat small intestine.
AB  - Acamprosate (calcium bis acetyl-homotaurine), a homotaurine derivative, a
      structural analogue of gamma-aminobutyric acid (GABA) and an upper homologue of
      taurine, is a relatively new drug used to prevent relapse in weaned alcoholics.
      When administered orally as enteric-coated tablets at relatively high doses, this
      drug has a bioavailability of about 11%; however, the intestinal absorption
      mechanism has not been studied in depth. The present study was therefore planned
      to characterize the intestinal transport of acamprosate in the rat and the effect
      of chronic alcohol treatment on this process, quantifying its kinetic parameters
      and investigating possible inhibitors. Using an in vitro technique, acamprosate
      absorption was measured in the rat intestine from three different groups: alcohol
      group [fed a liquid diet containing 5% (w/v) ethanol for 4 weeks], isocaloric
      pair-fed control, and a solid diet group. Intestinal acamprosate absorption was
      found to occur mainly by passive diffusion with a diffusive permeability of
      0.213+/-0.004 cm/h in control pair-fed animals, 0.206+/-0.001 cm/h in animals
      receiving chronic alcohol treatment, and 0.193+/-0.001 cm/h in the solid diet
      group. Inhibition studies showed that at a 10(-3) M acamprosate concentration,
      some compounds such as GABA, taurine, proline, and glycine at 40 mM each did not
      affect acamprosate transport. Nevertheless, when a lower concentration of the
      drug (10(-4) M) was assayed, a significant reduction of acamprosate transport in
      the presence of taurine or GABA 40 mM was found. These results suggest that
      acamprosate in the rat jejunum, could be transported, in part, by a carrier
      system. Further experiments using different concentrations of taurine (10, 20,
      and 80 mM) showed that the maximum inhibition (32%) is achieved at 20 mM of
      taurine. These latter results suggest that acamprosate and taurine share, at
      least, an intestinal carrier system in rat jejunum. From the above results, it
      can be concluded that there are probably two pathways involved in the intestinal
      absorption of acamprosate: passive diffusion and mediated transport, with the
      former being predominant. Moreover, neither chronic ethanol intake nor the type
      of diet seems to alter the intestinal absorption of the drug.

PMID- 10905993
TI  - Vinyl chloride: still a cause for concern.
AB  - Vinyl chloride (VC) is both a known carcinogen and a regulated chemical, and its
      production capacity has almost doubled over the last 20 years, currently 27
      million tons/year worldwide. According to recent reports it is still a cause for
      concern. VC has been found as a degradation product of chloroethylene solvents
      (perchloroethylene and trichloroethylene) and in landfill gas and groundwater at
      concentrations up to 200 mg/m(3) and 10 mg/L, respectively. Worldwide
      occupational exposure to VC still seems to be high in some countries (e.g.,
      averages of approximately 1,300 mg/m(3) until 1987 in one factory), and exposure
      may also be high in others where VC is not regulated. By combining the most
      relevant epidemiologic studies from several countries, we observed a 5-fold
      excess of liver cancer, primarily because of a 45-fold excess risk from
      angiosarcoma of the liver (ASL). The number of ASL cases reported up to the end
      of 1998 was 197 worldwide. The average latency for ASL is 22 years. Some studies
      show a small excess risk for hepatocellular carcinoma, and others suggest a
      possible risk of brain tumors among highly exposed workers. Lung cancer,
      lymphomas, or leukemia do not seem to be related to VC exposure according to
      recent results. The mutation spectra observed in rat and human liver tumors (ASL
      and/or hepatocellular carcinoma) that are associated with exposure to VC are
      clearly distinct from those observed in sporadic liver tumors or hepatic tumors
      that are associated with other exposures. In rats, the substitution mutations
      found at A:T base pairs in the ras and p53 genes are consistent with the
      promutagenic properties of the DNA adduct 1,N(6)-ethenoadenine formed from VC
      metabolites. Risk assessments derived from animal studies seem to overestimate
      the actual risk of cancer when comparing estimated and reported cases of ASL.

PMID- 10905996
TI  - Role of acetaldehyde in the induction of heart left ventricular atrial
      natriuretic peptide gene expression in rats.
AB  - We studied the effects of ethanol and acetaldehyde on myocardial gene expression
      of atrial natriuretic peptide (ANP) and growth of rats. Combined ethanol and
      calcium carbimide treatment increased blood-acetaldehyde levels and ANP mRNA
      levels by 40-60% in 2-8 day experiments, compared to the controls. The results
      suggest a role for acetaldehyde in the development of alcoholic heart
      dysfunction.

PMID- 10905994
TI  - A role for valproate in the treatment of sedative-hypnotic withdrawal and for
      relapse prevention.
AB  - In the human central nervous system, the gamma-aminobutyric acid (GABA) type A
      receptor complex undergoes changes with both acute and chronic exposure to
      sedative-hypnotic drugs. These changes contribute to both the acute effects of
      these drugs as well as the chronic effects of sedative-hypnotic dependence,
      withdrawal, and drug craving. Clinically these chronic effects are difficult to
      treat in patients dependent on ethanol or benzodiazepines. Valproate may return
      the GABA type A receptor function to a state more closely resembling its normal
      function. By this mechanism, it is possible to reduce the symptoms of sedative
      hypnotic withdrawal and relapse.

PMID- 10905997
TI  - Alterations in preimplantation in vivo development after preconceptional chronic
      moderate alcohol consumption in female mice.
AB  - Although many studies have explored the effects of acute or chronic ethanol
      exposure during the postimplantation period on embryo/fetal development, few
      reports have described the ethanol effects on preimplantation embryo development.
      Little is known about the effects of ethanol consumption prior to gestation on
      embryo growth. Recently, we have shown that chronic moderate ethanol intake by
      prepubertal female mice reduces the ovulatory response and impairs in vitro
      fertilization and in vitro embryo preimplantation development. The purpose of the
      present work was to evaluate the effects of preconceptional chronic moderate
      ethanol ingestion on preimplantation embryo morphology and differentiation, the
      timing of cleavage and embryo growth in vivo, and to determine the time pattern
      in which alterations appear. Prepubertal female mice were treated with 10% (w/v)
      ethanol for 30 days prior to conception. After inducing ovulation on day 27 and
      29 of the ethanol treatment, females were mated with control males and the day of
      presence of vaginal plug was day 1. On day 1, a decreased percentage of normal
      fertilized oocytes, elevated parthenogenetic oocyte activation and unfertilized
      eggs with abnormal metaphase II were found in ethanol-treated, compared to
      control females. On day 2, while any differences in the total percentage of 2
      cell embryos were observed, the treated females had a significantly higher
      percentage of morphologically abnormal embryos, compared to control females. On
      day 3, the preconceptional consumption of ethanol produced significantly reduced
      percentages of compacted morulae and an increased percentage of uncompacted
      morulae. The total percentage of morulae in the treated females was lower than in
      controls. On day 4, ethanol-treated females showed significantly decreased
      percentages of hatched attached blastocysts and increased early blastocyst and
      morula percentages, compared to controls. Thus, preconceptional chronic moderate
      ethanol ingestion by prepubertal female mice produced retarded development,
      impaired blastocyst hatching, abnormal embryo morphology and embryo loss by
      fragmentation due to alterations induced in the female gamete.

PMID- 10905998
TI  - Effects of pregnancy and progesterone on the consumption of ethanol by the high
      ethanol preferring (HEP) rat.
AB  - A significant fraction of women continue to drink heavily during pregnancy, which
      is associated with the fetal alcohol syndrome, alcohol-related birth defects,
      alcohol-related neurodevelopmental disorder, and spontaneous abortion. The
      objective of this study was to determine whether the selectively bred genetic
      drinking Myers High Ethanol Preferring (HEP) rat would continue to drink through
      pregnancy. Rats from the F7 generation were screened by a 10-day 3-30% (v/v)
      ethanol concentration 'step up' procedure in order to determine the concentration
      which resulted in maximal drinking with an ethanol solution to total fluid ratio
      closest to 0.5. After baseline drinking of the preferred concentrations was
      established, female HEP rats were randomly selected for mating and their ethanol
      bottles were removed. Upon finding a 'sperm plug', male rats were removed and the
      ethanol was returned. A second group received injections of progesterone in
      sesame oil beginning with a 1.0 mg/kg/day dose which was increased to 3.0
      mg/kg/day on gravid days (GD) 5-20. Vaginal smears confirmed that progesterone
      rendered the rats anoestrous. Neither pregnancy nor progesterone changed either
      the amount or proportion of ethanol consumed compared to the baseline period. The
      rats drank an average of 8.4 g/kg daily throughout pregnancy. A sharp drop in
      food intake was noted the day after mating. Beginning on GD 13, it was observed
      that pregnant rats showed a marked increase in the variance for proportion of
      ethanol consumed and body weight. Subsequently, only one of the eight impregnated
      rats successfully delivered a litter. The ethanol solution was removed and these
      rats mated again: seven of the eight rats delivered litters. These two findings
      suggest that the pregnant females must have begun to lose their litters on or
      after GD 13. Further, pregnancy does not affect the consumption of ethanol in the
      HEP rat. In addition, due to the fact that drinking by HEP rats during pregnancy
      leads to such a high rate of resorption of the fetus, this hybrid strain may also
      constitute a useful model for the study of alcohol-induced spontaneous abortion.

PMID- 10905999
TI  - Elevated homocysteine levels in alcohol withdrawal.
AB  - Ethanol exerts its behavioural effects largely by interacting with receptors for
      brain neurotransmitters. However, the molecular mechanisms involving these
      interactions and the pathogenesis of alcohol-withdrawal symptomatology are still
      not well understood. Until recently, no data were available about homocysteine
      (Hcy) levels in acute alcohol intoxication of chronic alcoholics and in patients
      undergoing withdrawal from alcohol. Hcy, blood-alcohol concentrations, vitamins
      B6, B12, and folate concentrations were assessed in 29 chronic alcoholics, who
      underwent withdrawal from alcohol. We observed increased Hcy levels in most
      patients. Hcy levels steadily decreased during the observation period. We
      postulate that hyperhomocysteinaemia and excitatory amino acid neurotransmitters,
      by their agonism at the N-methyl-D-aspartate receptor, may partly mediate alcohol
      associated withdrawal symptomatology. The importance of assessing serum Hcy
      levels in order to detect methylation deficiency in patients with chronic
      alcoholism and for possible therapeutic strategies is discussed.

PMID- 10906000
TI  - Serum carotenoids are associated with increased lung cancer risk among alcohol
      drinkers, but not among non-drinkers in a cohort of tin miners.
AB  - To examine the association between pre-diagnostic serum carotenoid levels and
      lung cancer risk and the effects of alcohol intake on the carotenoid-lung cancer
      relationship, we conducted a case-control study in an occupational cohort from
      the Yunnan Tin Corporation in China. During 6 years of follow-up, 339 cases of
      confirmed lung cancer were diagnosed. Among these cases, those who donated pre
      diagnostic blood (n = 108) were eligible for this study. For each case, two
      individuals alive and free of cancer at the time of case diagnosis, matched on
      age, sex, and date of blood collection, were selected as controls. Serum beta
      carotene (odds ratios (ORs) for tertiles: 1, 1.3, 2.0) and beta-cryptoxanthin
      (ORs for tertiles: 1, 1.8, 2.9) levels were positively associated with lung
      cancer risk after adjustment for tobacco use and radon exposure. Among alcohol
      drinkers, higher serum carotenoid levels were significantly associated with
      increased lung cancer risk (alpha-carotene OR 2.2, 95% confidence interval (CI)
      1.1-4.4, beta-carotene OR 7.6, 95% CI 3.1-18.6, lutein/zeaxanthin OR 2.3, 95% CI
      1.2-6.6 and beta-cryptoxanthin OR 7.6, 95% CI 2.7-21.5). Conversely, risk
      estimates among non-drinkers suggest a possible protective association for higher
      carotenoid levels.

PMID- 10906001
TI  - The specificity of disrupted processes in families of adult children of
      alcoholics.
AB  - Children of alcoholics (COAs) have been characterized as an at-risk population in
      part, because of the dysfunctional family environments that disrupt psychosocial
      development among offspring exposed to parental alcoholism. This study examined
      the specificity of problematic family environments to children of alcoholics vs
      children exposed to other significant family stressors that included parental
      death, unemployment, separation, divorce, or major illness. University students
      completed self-report measures of family stressors, family relationship problems,
      family communication quality, family conflict, and relationship with parents.
      Based on a family stressor checklist, 20 students exposed only to parental
      alcoholism and no other family stressors were compared to several other groups
      exposed to specific family stressors, and to 50 control subjects who had reported
      no family stressors. Results showed that students from families where a parent is
      or was an alcoholic, and where there were no other family stressors, recall
      disturbed family relations no more commonly than students specifically exposed to
      other family stressors such as parental divorce, death, or major illness, and no
      more commonly than those who reported no family stressors. Further analyses
      suggest that the disruption of COAs' family environments may be explained by
      their increased likelihood of experiencing additional family stressors that can
      have a disruptive effect, such as parental separation, divorce and unemployment.

PMID- 10906002
TI  - Gender and peripheral neuropathy in chronic alcoholism: a clinical
      electroneurographic study.
AB  - In some alcohol-related pathologies of chronic alcoholism women are more
      vulnerable than men. A consecutive sample of 62 chronic alcoholics was studied,
      18 females and 44 males, aged between 28 and 69 years to assess the incidence and
      distribution of peripheral neuropathy with regard to gender. All patients
      underwent clinical and neurological observations, laboratory tests, and
      electroneurography. Total lifetime dose of ethanol (TLDE) and other risk factors
      for neuropathy (disease duration, age, nutritional status) were calculated and
      correlated to sural nerve sensory-evoked potential (SEP) amplitude. In 42
      patients (67.7%), we observed the presence of clinical and/or infraclinical
      neuropathy, mostly axonal, in 29 males (65.9%) and 13 females (72.2%). In women,
      compared to men, TLDE and disease duration were significantly inversely
      correlated to sural nerve SEP amplitude, i.e. in women, SEP amplitude is
      significantly reduced in relation to TLDE and disease duration increase. These
      data indicate a higher sensitivity of females towards the toxic effects of
      ethanol, other than malnutrition, on peripheral nerve fibres.

PMID- 10906003
TI  - Compliance rate and associated factors for entering an alcohol brief intervention
      treatment programme.
AB  - The study aim was to ascertain the compliance rate and to compare associated
      factors among heavy drinkers willing and unwilling to enter an alcohol brief
      intervention treatment programme. Patients aged 20-60 years visiting five primary
      healthcare clinics for any reason were both asked to complete a health
      questionnaire and interviewed to identify early phase heavy drinkers and to
      collect sociodemographic and health data. About half of the heavy drinkers
      (487/1011) complied with a recommendation for brief intervention. Gender, age,
      drinking variables, smoking, and exercise were associated with compliance. Women
      and young adults are subgroups of heavy drinkers whose compliance was lower than
      others and special attention should be given to them when planning brief
      intervention strategies.

PMID- 10906005
TI  - Side-bias in alcohol and heroin addicts.
AB  - Alcoholics, heroin addicts and normal controls were asked for their degree of
      preference for the two lateral (left, right) sides during their performance of
      unilateral activities involving one of the four paired organs, hand, foot, eye
      and ear. Side-bias was assessed by a questionnaire, with 22 items for hand
      preference, and five items each for foot, eye and ear preference. Group
      difference was assessed with a mixed-factorial design (Group x Side) for each
      form of side-bias. Unlike heroin addicts and normal controls, alcoholics
      exhibited a significant reduction in right side-bias for all four measures, which
      suggests an anomalous pattern of lateralization.

PMID- 10906004
TI  - Transient increase in platelet monoamine oxidase b activity during early
      abstinence in alcoholics: implications for research.
AB  - Some earlier studies have suggested that platelet monoamine oxidase (MAO)-B
      activity should be determined at time points other than early in the abstinence
      phase. However, the optimal times for blood sampling have not been precisely
      defined. We therefore assessed platelet MAO-B activity repeatedly in 13 male
      alcohol-dependent patients over the 2 months after the end of a period of heavy
      alcohol intake. Twelve healthy men were used as controls. In the alcohol
      dependent patients, platelet MAO-B activity was transiently increased from 2 to 6
      weeks after the end of alcohol intake and the values during this time period were
      not different from those of controls. Platelet MAO-B activity was, however,
      significantly lower in the alcohol-dependent patients at 1 week and at 2 months
      after the end of alcohol intake, in comparison to controls. It is concluded that
      the transient increase in platelet MAO-B activity after the end of alcohol intake
      in alcohol-dependent patients may conceal a difference from a control group.
      Therefore, it is suggested that when platelet MAO-B activity is determined, the
      preferential time point for obtaining those values in alcohol-dependent patients
      is after 2 months of abstinence.

PMID- 10906006
TI  - The effects of ritanserin on mood, sleep, vigilance, clinical impression, and
      social functioning in alcohol-dependent individuals. Ritanserin in Alcoholism
      Work Group.
AB  - In an international double-blind placebo-controlled trial with 493 detoxified
      alcohol-dependent individuals, ritanserin, a specific 5-hydroxytryptamine,
      antagonist, was tested in three different dosages (2.5, 5, and 10 mg/day) against
      placebo over a period of 6 months. Data on changes in mood state, sleep quality,
      morning vigilance, clinical impression, and social functioning were analysed.
      None of the three dosages of ritanserin given revealed any significant effect
      against placebo on the above-mentioned parameters either at the end of treatment
      or upon relapse. Therefore, we conclude that patients suffering from alcohol
      dependence without concomitant psychiatric disorders do not benefit from
      additional treatment with (2.5, 5, or 10 mg/day) ritanserin.

PMID- 10906007
TI  - Platelet serotonin uptake is higher in early-onset than in late-onset alcoholics.
AB  - The main objective of this study was to compare platelet serotonin (5-HT) uptake
      between early-onset alcoholics (EOA) and late-onset alcoholics (LOA). Subjects
      were 24 dependent male alcoholic in-patients and 21 healthy control subjects. 5
      HT uptake was quantified by incubating platelets with [3H]5-HT at various
      concentrations (0.5 to 1000 nM). 5-HT uptake was higher in EOA, compared to both
      the LOA and control groups (P < 0.02) at the highest 5-HT concentration (1000
      nM). No significant difference was found between LOA and controls or between EOA
      + LOA and controls. Previous studies have shown that 5-HT uptake was higher in
      platelets, lymphocytes, and brain of alcoholics vs controls, but our data suggest
      that higher platelet serotonin transporter function is limited to EOA, not LOA.

PMID- 10906008
TI  - The concept of abnormal hemispheric organization in addiction research.
AB  - In addition to the established areas of endogenous psychoses, the concept of
      abnormal hemispheric organization in the field of psychiatry is also generating
      ever greater interest in the area of research into addiction. On the basis of the
      demonstrably higher rate of developmental risk factors (pre-, peri-, postnatal),
      in particular the marker left-handedness (LH) has been interpreted as an
      indication of induced hemispheric 'malcontrol' in endogenous psychoses. In
      various studies, elevated rates of LH have also been shown in alcoholics.
      Alcoholism could be related to biological factors associated with anomalous
      cerebral dominance. In a joint study carried out by the Anton Proksch Institut in
      Vienna (Austria), and the University of Erlangen-Nuremberg (Germany) involving a
      total of 250 alcohol-dependent inpatients, the hypothesis of deviant laterality
      in the presence of an elevated frequency of developmental risk factors has been
      confirmed exclusively in male alcoholics. A comparison of subtypes has also
      revealed that Type IV in the Lesch typology, and Type II in the Cloninger
      classification, are more vulnerable subtypes. These results clearly show that
      there are differences to be found within the overall group of alcoholics, and
      underscore the need for subtyping and gender-specific studies.

PMID- 10906009
TI  - Diagnosing the full spectrum of fetal alcohol-exposed individuals: introducing
      the 4-digit diagnostic code.
AB  - The medical/research records of 1014 patients diagnosed at the Washington State
      Fetal Alcohol Syndrome (FAS) Diagnostic and Prevention Network (DPN) of clinics
      were used to develop a new, comprehensive, reproducible method for diagnosing the
      full spectrum of outcomes among patients with prenatal alcohol exposure. This new
      diagnostic method, called the 4-Digit Diagnostic Code, was compared to the
      standard gestalt method of diagnosis on the first 454 patients who had received a
      gestalt diagnosis of FAS, atypical FAS (AFAS) or possible fetal alcohol effect
      (PFAE) prior to the development of the 4-Digit Diagnostic Code. The outcomes of
      the patients were more accurately and comprehensively documented by the 4-Digit
      Diagnostic Code, because of its use of quantitative, objective measurement scales
      and specific case definitions. The four digits in the code reflect the magnitude
      of expression of the four key diagnostic features of FAS in the following order:
      (1) growth deficiency; (2) the FAS facial phenotype; (3) central nervous system
      damage/dysfunction; (4) gestational alcohol exposure. The magnitude of expression
      of each feature is ranked independently on a four-point Likert scale with 1
      reflecting complete absence of the FAS feature and 4 reflecting a strong
      'classic' presence of the FAS feature. The 4-Digit Diagnostic Code is being used
      effectively for diagnosis, screening, and surveillance efforts in all Washington
      State FAS DPN clinics.

PMID- 10906010
TI  - Training and dealing with errors or mistakes in medical practical procedures.

PMID- 10906012
TI  - Is the ethos of medical practice in community paediatrics compatible with that in
      public health?

PMID- 10906011
TI  - Intracytoplasmic sperm injection and other aspects of new reproductive
      technologies.

PMID- 10906013
TI  - Surviving chronic physical illness: psychosocial outcome in adult life.

PMID- 10906014
TI  - Twelve year outcomes following bacterial meningitis: further evidence for
      persisting effects.
AB  - AIM: To determine whether intellectual and cognitive impairments observed seven
      years following early childhood bacterial meningitis persist into adolescence.
      METHODS: Blinded neuropsychological, auditory, and behaviour assessments were
      conducted in 109 (69%) subjects from an original cohort of 158 children, seven
      and 12 years after their meningitis, and in 96 controls. RESULTS: Meningitis
      subjects remained at greater risk than controls for any disability (odds ratio OR
      4.7, confidence interval 2.2 to 9.6). Those with acute neurological complications
      had more sequelae than children with uncomplicated meningitis or controls (47% v
      30% v 11.5% respectively; p < 0.001). Differences in intellectual, academic, and
      high level cognitive function between subjects and controls were maintained at
      the seven and 12 year assessments. In contrast, lower order skills improved,
      while behaviour scores deteriorated significantly (p = 0.033). CONCLUSIONS: Many
      of the deficits identified at the seven year follow up persist 12 years after an
      episode of bacterial meningitis.

PMID- 10906016
TI  - Neutralising enterotoxin

PMID- 10906015
TI  - Parental smoking, socioeconomic factors, and risk of invasive meningococcal
      disease in children: a population based case-control study.
AB  - AIMS: To investigate the effects of parental smoking, socioeconomic
      characteristics, and indoor environment on the risk of invasive meningococcal
      disease in children. METHODS: Population based case-control study. A total of 68
      incident cases of invasive meningococcal disease in children less than 15 years
      old were compared with 135 controls selected from the same school and matched for
      year of birth, sex, and place of residence. Information on exposures was obtained
      in interviews with parents. RESULTS: Invasive meningococcal disease was strongly
      associated with parental smoking; rate ratios adjusted for socioeconomic factors
      were 3.5 (95% confidence interval 1.4-8.7) for smoking of mother, 3.2 (1.5-6.9)
      for smoking of father, and 2.7 (1.3-5.4) for every 20 cigarettes smoked at home
      on an average day. The risk of the disease was strongly inversely related to
      maternal education and, less strongly, to ownership of a car and of a weekend
      house, father's education, crowding, and the number of siblings, but these
      associations were reduced or eliminated in multivariate models. The type of
      heating and cooking (used as proxies for indoor air pollution) were not
      associated with the disease. CONCLUSION: The risk of invasive meningococcal
      disease in children is strongly influenced by parental smoking and unfavourable
      socioeconomic circumstances.

PMID- 10906017
TI  - Hospitalisation for RSV infection in ex-preterm infants-implications for use of
      RSV immune globulin.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) specific immune globulin is now
      being marketed for prevention of RSV infection in ex-preterm infants. However,
      there are no published UK data on the morbidity or mortality from RSV in these
      infants. AIMS: To determine the morbidity and mortality from RSV infection in a
      cohort of infants previously treated at a regional neonatal unit, and compare the
      cost of hospitalisation for RSV with the potential cost of administering RSV
      immune globulin (RSV-IG) prophylaxis. METHODS: Infants born at a gestation of
      less than 32 weeks were studied. Details of admissions for respiratory illness in
      the first two years of life were collected from hospital records, referring
      hospitals, and general practitioners. RESULTS: Data on 82 infants were collected.
      Up to three RSV seasons were encountered. The hospitalisation rate for confirmed
      RSV infection for the first season encountered was 4%. Rates of ward and
      paediatric intensive care unit admission were higher for infants with chronic
      lung disease. There were no deaths from RSV. RSV-IG would not have been cost
      effective for most infants. CONCLUSION: The morbidity and mortality rates from
      RSV observed in this group do not support the widespread introduction of RSV-IG
      prophylaxis for ex-preterm infants.

PMID- 10906018
TI  - Re-vaccination of 421 children with a past history of an adverse vaccine reaction
      in a special immunisation service.
AB  - BACKGROUND: In Australia an adverse event following immunisation (AEFI), with the
      exception of anaphylaxis and encephalopathy, is no longer considered an absolute
      contraindication to continuing vaccination with the suspect vaccine. Despite
      these recommendations there is a paucity of information on the re-vaccination of
      such children. AIMS: To describe the re-vaccination of a large number of children
      with a past history of an AEFI. METHODS: A review of children attending special
      immunisation services in three Australian tertiary care paediatric centres.
      RESULTS: During the review 970 children attended of whom 469 had experienced a
      past AEFI. Of these, 293 had experienced minor while 176 children had experienced
      significant neurological or allergic reactions. The majority (421/469) were re
      vaccinated, with only one child having a significant neurological event; this was
      transient and resolved spontaneously. CONCLUSIONS: Re-vaccination of children who
      have a past history of an AEFI appears safe. A special immunisation service
      should be part of a comprehensive immunisation programme.

PMID- 10906019
TI  - Follow up study eight years after diagnosis of sexual abuse.
AB  - AIM: To study the outcome over an eight year period of children determined by
      paediatricians in 1989 as definitely or probably sexually abused. METHOD:
      Information was obtained on 140 of 148 children diagnosed in 1989 when aged 7 or
      less. Sources were hospital medical records and school health records. School
      health records of a comparison group of 83 children were also examined. RESULTS:
      A variety of problematic characteristics were found significantly more often in
      the abused group than the comparison group. These included surname changes (30% v
      2%), removal from home (25% v 1%), number of home addresses (2.8 v 1.4), and
      schools attended (3.4 v 2.2). Other significant findings included further abuse
      (35% v 0%), adverse behaviours (60% v 16%), educational problems (24% v 5%),
      chronic health problems (54% v 36%), and involvement of mental health services
      (32% v 1%).

PMID- 10906020
TI  - Detrusor instability; day and night time wetting, urinary tract infections.

PMID- 10906021
TI  - Treatment of thoracic lymphangiomatosis.

PMID- 10906022
TI  - Advances in the understanding of tuberous sclerosis.

PMID- 10906023
TI  - Intravenous pamidronate in juvenile osteoporosis.
AB  - AIMS: To investigate the use of the aminobisphosphonate, disodium pamidronate, in
      children with vertebral osteoporosis. METHODS: Five children (aged 10-15 years)
      with vertebral osteoporosis who developed compression fractures in the thoracic
      and/or lumbar spine as a consequence of five different conditions, received
      treatment with intravenous disodium pamidronate in doses ranging from 0.5 to 12
      mg/kg/y. RESULTS: Each child had rapid pain relief following the first treatment,
      followed by large increments in lumbar spine bone density over one year; the
      change in bone density standard deviation score ranged from 0.5 to 2.5 with
      percentage increments of 26% to 54%. CONCLUSION: Intravenous pamidronate appears
      to be a useful therapeutic option in childhood osteoporosis, but its use in
      children must still be regarded as experimental and therefore closely monitored.

PMID- 10906024
TI  - Bone metabolism and mineral density following renal transplantation.
AB  - AIM: To study bone turnover following renal transplantation using a panel of
      biochemical markers and to correlate the results with both areal and volumetric
      bone mineral density (BMD). PATIENTS: A total of 31 patients aged 18.1 years were
      transplanted 5.4 years before this study. Control patients (n = 31) were age and
      gender matched. METHODS: In addition to measurement of biochemical markers, BMD
      was measured by single photon absorptiometry and peripheral quantitative computed
      tomography on the non-dominant radius. RESULTS: Patients had reduced glomerular
      filtration rate, raised concentrations of serum phosphate, serum procollagene
      type I carboxy terminal propeptide, osteocalcin, and serum procollagene type I
      cross linked carboxy terminal telopeptide. The differences were still significant
      if only patients with normal intact parathyroid hormone were considered. BMD
      single photon absorptiometry Z score for age was significantly decreased.
      Following standardisation for height the differences were no longer present. With
      volumetric techniques patients had normal trabecular but decreased cortical and
      total BMD compared to age matched controls, but there was no difference from
      height matched controls. CONCLUSION: Markers of bone turnover are increased
      following renal transplantation. However, the biochemical analysis did not allow
      conclusions to be drawn on the bone mineral content. BMD single photon
      absorptiometry Z score corrected for height and BMD measured by quantitative
      computed tomography compared to height matched controls were normal in paediatric
      renal transplantation patients. Height matched controls should be used in both
      areal and volumetric BMD measurements in states of growth failure.

PMID- 10906026
TI  - Rapid responses

PMID- 10906025
TI  - Idiopathic pulmonary fibrosis in infants: good prognosis with conservative
      management.
AB  - BACKGROUND: Pulmonary interstitial fibrosis in children is a disease of unknown
      aetiology, usually associated with a poor prognosis. METHODS: In this case series
      we describe 11 children presenting over a 10 year period, managed conservatively
      and associated with a good prognosis. RESULTS: In six, symptoms were present from
      birth and 10 had symptoms at or before 3 months. Diagnosis was made using chest
      computed tomography and percutaneous lung biopsy. All patients were treated with
      oral prednisolone. In five no steroid response was noted. One patient responded
      to hydroxychloroquine. Home oxygen was required in five patients. At follow up
      all patients are alive at a median age of 6 years (range 1 to 12 years). The two
      recently diagnosed children have significant symptoms, seven have dyspnoea on
      exercise, and two are symptom free. CONCLUSION: The good prognosis seen in these
      patients is different to previous case reports, indicating a greater than 50%
      mortality.

PMID- 10906028
TI  - Superior vena cava thrombosis causing respiratory obstruction successfully
      resolved by stenting in a small bowel transplant candidate.
AB  - A 4 year old child was referred for small bowel transplantation. He had superior
      vena cava obstruction secondary to numerous central venous line placements;
      alternative routes for long term central venous access were compromised by
      extensive venous occlusive disease. Patency for the superior vena cava was re
      established with stenting, which allowed for radiological placement of another
      central venous line. Long term survival in infants and young children with
      intestinal failure is dependent on adequate central venous access for the
      administration of parenteral nutrition. Line sepsis and physical damage to the
      catheter often necessitates multiple central venous catheter placements during
      their early life and these children are at risk of catheter related veno
      occlusive disease. Recurrent sepsis and the loss of satisfactory venous access
      for the administration of parenteral nutrition is life threatening and is an
      indication for intestinal transplantation in up to 41% of patients reported by
      the small bowel registry.

PMID- 10906027
TI  - Effect of oral glucocorticoid treatment on serum inflammatory markers in acute
      asthma.
AB  - BACKGROUND: Acute asthma is associated with elevated serum concentrations of
      products of activated T cells and eosinophils. AIMS: To compare the changes in
      concentrations of these products with disease severity and changes in lung
      function following oral prednisolone treatment. METHODS: Twenty patients (mean
      age 8.7 years) were recruited on admission with acute asthma to a district
      general hospital. Disease severity was recorded before and after treatment with
      oral prednisolone using a validated pulmonary index score. Serum concentrations
      of interleukin (IL)-4, IL-5, soluble (s)CD25 (soluble IL-2 receptor), using a
      specific enzyme linked immunosorbent assay, and eosinophil cationic protein
      (ECP), using radioimmunoassay, were measured concomitantly. Non-asthmatic
      children (n = 6, mean age 9.2 years) undergoing elective surgery were recruited
      as controls, and serum samples were obtained on one occasion without treatment.
      Main outcome measures were changes in serum concentrations of cytokines and ECP,
      clinical asthma severity score, and peak expiratory flow rate. RESULTS: As
      expected, oral glucocorticoid treatment in the children with asthma was
      associated with clinical improvement and also with significant reductions in
      serum concentrations of IL-5 (mean 5.59 to 2.19 pg/ml, p = 0.0001), sCD25 (mean
      2236 to 1772 pg/ml, p = 0.002), and ECP (mean 54.3 to 33. 1 pg/ml, p = 0.0001).
      Serum IL-4 concentrations, in most patients and all the controls, remained below
      the sensitivity of the assay. However, serum concentrations of IL-5, sCD25, and
      ECP remained significantly higher than in controls, even after treatment with
      oral glucocorticoids (p = 0.03). CONCLUSIONS: These data suggest that T cell
      mediated inflammation may persist in childhood asthma despite apparent clinical
      remission associated with conventional doses of prednisolone. The long term
      consequences of persistent inflammation after an apparently treated acute attack
      of asthma require clarification. Clinical assessment and pulmonary function are
      inadequate surrogates for airway inflammation.

PMID- 10906029
TI  - An unusual concurrence of graft versus host disease caused by engraftment of
      maternal lymphocytes with DiGeorge anomaly.
AB  - We describe a girl with DiGeorge anomaly and normal cytogenetic and molecular
      studies, whose clinical course was complicated by graft versus host disease
      caused by intrauterine materno-fetal transfusion, and several immunohematological
      alterations including a monoclonal gammapathy of undetermined significance (first
      IgG, which subsequently changed to IgM). The main clinical features and
      pathological findings are discussed.

PMID- 10906030
TI  - Invasion by human herpesvirus 6 and human herpesvirus 7 of the central nervous
      system in patients with neurological signs and symptoms.
AB  - METHODS: A total of 43 children with neurological signs and symptoms were
      enrolled in the study. All children were suspected of having meningitis, and
      lumbar punctures were performed. Human herpesvirus 6 (HHV-6) and HHV-7 DNA was
      detected in cerebrospinal fluid (CSF) and peripheral blood mononuclear cells
      (PBMC) by nested polymerase chain reaction. RESULTS: Most patients had detectable
      serum antibody to both HHV6 and 7. HHV6 DNA was detected in PBMC of 15 patients
      and in CSF cell pellet of seven. Corresponding figures for HHV7 were 28 and
      6.2/7, and 5/6 with CSF viral DNA also had it in PBMC, respectively. No viral DNA
      was detected in CSF supernatants. The seven HHV6 CSF viruses were all variant B.
      CONCLUSION: These data suggest that HHV-7 may invade the CNS.

PMID- 10906031
TI  - Immune response to gangliosides in a case of Guillain-Barre syndrome after
      varicella.
AB  - An 8 year old girl was admitted to hospital with the typical clinical features of
      Guillain-Barre syndrome (GBS) after recovering from varicella. Onset of the
      disease was just two weeks after the onset of varicella in her young sister.
      Examination of cerebrospinal fluid and nerve conduction studies showed typical
      findings of GBS. Although serum from both the patient and sister were analysed
      for autoantibodies to gangliosides and myelin P0 protein, IgM anti-GM1 antibody
      and anti-GD1b antibody were only detected in the patient. HLA DR haplotypes were
      quite different between the two subjects. This suggests that these autoantibodies
      may play an important role in the pathogenesis of GBS after varicella zoster
      virus infection.

PMID- 10906032
TI  - Mercury intoxication presenting with tics.
AB  - A 5 year old Chinese boy presented with recurrent oral ulceration followed by
      motor and vocal tics. The Chinese herbal spray he used for his mouth ulcers was
      found to have a high mercury content. His blood mercury concentration was raised.
      Isolated tics as the sole presentation of mercury intoxication has not previously
      been reported.

PMID- 10906033
TI  - Which children should receive growth hormone treatment. Reserve it for the GH
      deficient.

PMID- 10906034
TI  - Circadian rhythm of heart rate and heart rate variability.
AB  - BACKGROUND: Measurements of heart rate variability (HRV) are increasingly used as
      markers of cardiac autonomic activity. AIM: To examine circadian variation in
      heart rate and HRV in children. SUBJECTS: A total of 57 healthy infants and
      children, aged 2 months to 15 years, underwent ambulatory 24 hour Holter
      recording. Monitoring was also performed on five teenagers with diabetes mellitus
      and subclinical vagal neuropathy in order to identify the origin of the circadian
      variation in HRV. METHODS: The following variables were determined hourly: mean
      RR interval, four time domain (SDNN, SDNNi, rMSSD, and pNN50) and four frequency
      domain indices (very low, low and high frequency indices, low to high frequency
      ratio). A chronobiological analysis was made by cosinor method for each variable.
      RESULTS: A significant circadian variation in heart rate and HRV was present from
      late infancy or early childhood, characterised by a rise during sleep, except for
      the low to high frequency ratio that increased during daytime. The appearance of
      these circadian rhythms was associated with sleep maturation. Time of peak
      variability did not depend on age. Circadian variation was normal in patients
      with diabetes mellitus. CONCLUSION: We have identified a circadian rhythm of
      heart rate and HRV in infants and children. Our data confirm a progressive
      maturation of the autonomic nervous system and support the hypothesis that the
      organisation of sleep, associated with sympathetic withdrawal, is responsible for
      these rhythms.

PMID- 10906036
TI  - Editor's preface

PMID- 10906035
TI  - Reliability of percentage ideal weight for height.
AB  - AIMS: To assess the reliability of percentage ideal weight for height (%WFH) as a
      measure in children. METHODS: Forty two dietitians calculated %WFH of six
      children. Eleven of the 42 repeated the calculations. RESULTS: Interexaminer
      estimates varied by 16.5 to 40 percentage points (mean 27.8). Intraexaminer
      variability was also large. CONCLUSIONS: %WFH is an unreliable measure of
      nutritional status.

PMID- 10906037
TI  - Getting sperm and egg together: things conserved and things diverged.
AB  - Sperm-egg interactions occur at multiple levels on the egg surface, first with
      the egg's extracellular matrix and then with the egg's plasma membrane. The
      BioPore minisymposium on "The Egg Surface" at the 1999 annual meeting of the
      Society for the Study of Reproduction highlighted a series of events underlying
      successful interactions of the sperm with the egg: 1) composition, synthesis, and
      assembly of the mouse egg's extracellular matrix, the zona pellucida, during
      oogenesis; 2) oocyte maturation and development of the sperm-binding domain of
      mouse eggs; and 3) characterization of functional domains in different sperm
      ligands (fertilin-alpha and fertilin-beta in the mouse and lysin in the abalone)
      that recognize cognate binding sites on the egg surface. Data that were presented
      are reviewed here and discussed with respect to conserved and divergent features
      of gamete functions.

PMID- 10906038
TI  - Expression of estrogen receptor coactivators in the rat uterus.
AB  - Nuclear receptor coactivators associate in a ligand-dependent manner with
      estrogen receptors (ER) and other nuclear receptors, and they enhance ligand
      dependent transcriptional activation. This study examined basal coactivator
      expression in rat uterus to investigate if expression of these genes is regulated
      by estradiol-17 beta or tamoxifen. Ovariectomized mature and immature rats were
      injected with estradiol-17 beta, tamoxifen, or vehicle (i.e., sesame oil) alone.
      Uteri were collected and analyzed for changes in coactivator mRNA expression
      using Northern blot and in situ hybridization analyses. Constitutive uterine mRNA
      expression of switch protein for antagonist (SPA), SRC-1, GRIP1, RAC3, RIP140,
      and p300 mRNAs was observed in control uteri, and treatment with ER ligands did
      not alter coactivator mRNA levels. The data suggest that expression of these
      coactivator genes is not sensitive to estradiol or tamoxifen in the rat uterus.
      No cell type-specific pattern of expression was apparent in uterine sections from
      mature and immature rats; however, silver grains were more abundant in luminal
      and glandular epithelial cells compared with the stroma and myometrium,
      indicating that coactivator mRNA levels vary among the uterine compartments.
      Thus, to our knowledge, we show for the first time that there is constitutive
      expression of several uterine nuclear receptor coactivators in a physiological
      setting that remains insensitive to estrogenic regulation. Furthermore, we
      speculate that higher constitutive levels of coactivator expression in glandular
      and luminal epithelial cells may be associated with increased hormonal
      responsiveness by these uterine compartments.

PMID- 10906039
TI  - Effects of androgen on androgen receptor expression in rat testicular and
      epididymal cells: a quantitative immunohistochemical study.
AB  - Androgen is essential for maintenance of spermatogenesis in the testis and for
      maturation of spermatozoa in the epididymis. The effects of androgen are mediated
      through its receptor (AR), the levels of which are, in turn, regulated by
      androgen. Previous studies have shown that AR concentrations in Leydig and
      Sertoli cells are differentially regulated during development. The aim of the
      present study was to determine if cell-type-specific regulation of AR by androgen
      occurs in testicular and epididymal cells during adulthood. Adult male rats were
      treated with the LHRH-antagonist Azaline B (100 g/day) by osmotic pump for 1, 2,
      3, 4, or 8 wk to suppress endogenous androgen, with identical numbers of intact
      control animals at each time period. An androgen replacement group was
      simultaneously treated with the antagonist and a synthetic androgen, 7 alpha
      methyl-19-nortestosterone (MENT), during the final 4 wk of the experiment. Levels
      of nuclear AR protein in specific cell types were quantified by
      immunohistochemistry in conjunction with computer-assisted image analysis. Levels
      of AR in testicular cells declined sharply after treatment with the LHRH
      antagonist. In Sertoli cells, nuclear AR levels decreased to 8% of control (P <
      0. 01) after 4 wk treatment; and to 12% and 17% of control (P < 0.01) in Leydig
      and myoid cells, respectively. Androgen replacement resulted in complete recovery
      of nuclear AR levels in Sertoli cells (93%, P > 0.05) but in only partial
      recovery in myoid (69%, P < 0. 01) and Leydig cells (56%, P < 0.01). In the
      epididymis, tubular epithelial cells and stromal cells differed in their
      responses to the LHRH antagonist. After 1 wk, nuclear AR levels in caput stromal
      cells decreased dramatically to 34% of control (P < 0.01) and in cauda stromal
      cells to 43% (P < 0.01). In contrast, the decline of AR levels in epididymal
      epithelial cells was not as dramatic as that in stromal cells. After 1 wk, the
      decline in the caput and cauda was to 87% and 76% of control, respectively. After
      8 wk, nuclear AR levels in stromal cells further declined to 1.1% in caput and
      1.4% in cauda, whereas in the epithelial cells, a smaller decline in nuclear AR
      was noted (to 30% in the caput and 45% in the cauda). After androgen replacement
      with MENT, nuclear AR levels recovered to more than 90% of control in both
      epididymal cell types. These results indicate that AR levels in the nuclei of
      adult Sertoli cells depend mainly on the level of androgen, whereas in the adult
      Leydig and myoid cells, the androgen dependency is more limited. The results also
      indicate that in the epididymis, stromal cells are more sensitive than epithelial
      cells to the regulation of AR levels by androgen.

PMID- 10906041
TI  - Selection of the dominant follicle in cattle: role of estradiol.
AB  - Involvement of estradiol in the deviation in growth rates between the two largest
      follicles of a wave was studied in 39 heifers. In experiment 1, the largest
      follicle remained intact in a control group and was ablated in five estradiol
      treated groups when the largest follicle reached 8.5 mm or larger (expected
      beginning of deviation; Hour 0). The ablation groups were given a single
      injection of 0, 0.004, 0.02, 0.1, or 0.5 mg of estradiol. Blood samples were
      taken from a jugular vein every hour at Hours 0 to 16. By Hour 8, FSH
      concentrations were greater (P < 0.05) in the ablation group that received 0 mg
      of estradiol than in the controls. Among the estradiol groups, that receiving
      0.02 mg had the lowest detectable increase in estradiol. In this group, FSH
      concentrations were not suppressed below the control concentrations, but the
      increase in FSH concentrations following ablation of the largest follicle was
      delayed for 2 or 3 h. This delay in the increase of FSH concentrations
      corresponded to the hours that estradiol was maximal. In experiment 2, blood
      samples were taken every 4 h from the caudal vena cava cranial to the junction
      with the ovarian veins in heifers with the largest follicle intact (controls) or
      ablated at 8.5 mm or larger (Hour 0). Averaged over Hours 4 to 48, estradiol
      concentrations were higher (P < 0.04) in the controls than in the ablation group.
      During Hours 0 to 12, estradiol concentrations increased (P < 0.05) in the
      controls, whereas FSH concentrations decreased (P < 0.05). In the ablation group,
      estradiol concentrations were lower than in the controls by Hour 4, and FSH
      concentrations increased (P < 0.05) between Hours 4 and 12. These results support
      the hypothesis that the largest follicle releases increased estradiol into the
      blood at the beginning of follicular deviation, and that the released estradiol
      is involved in the continuing depression of FSH concentrations to below the
      requirement of the smaller follicles.

PMID- 10906040
TI  - Administration of prostaglandin f(2 alpha) during the early bovine luteal phase
      does not alter the expression of ET-1 and of its type A receptor: a possible
      cause for corpus luteum refractoriness.
AB  - Luteal regression is initiated by prostaglandin F(2 alpha) (PGF(2 alpha)). In
      domestic species and primates, demise of the corpus luteum (CL) enables
      development of a new preovulatory follicle. However, during early stages of the
      cycle, which are characterized by massive neovascularization, the CL is
      refractory to PGF(2 alpha). Our previous studies showed that endothelin-1 (ET-1),
      which is produced by the endothelial cells lining these blood vessels, plays a
      crucial role during PGF(2 alpha)-induced luteolysis. Therefore, in this study, we
      compared the effects of PGF(2 alpha) administered at the early and mid luteal
      phases on ET-1 and its type A receptors (ETA-R) along with plasma ET-1 and
      progesterone concentrations, and the mRNA levels of PGF(2 alpha) receptors (PGF(2
      alpha)-R) and steroidogenic genes. As expected, ET-1 and ETA-R mRNA levels were
      markedly induced in midcycle CL exposed to luteolytic dose of PGF(2 alpha)
      analogue (Cloprostenol). In contrast, neither ET-1 mRNA nor its receptors were
      elevated when the same dose of PGF(2 alpha) analogue was administered on Day 4 of
      the cycle. In accordance with ET-1 expression within the CL, plasma ET-1
      concentrations were significantly elevated 24 h after PGF(2 alpha) injection only
      on Day 10 of the cycle. The steroidogenic capacity of the CL (plasma progesterone
      as well as the mRNA levels of steroidogenic acute regulatory protein and
      cytochrome P450(scc)) was only affected when PGF(2 alpha) was administered during
      midcycle. Nevertheless, PGF(2 alpha) elicited certain responses in the early CL:
      progesterone and oxytocin secretion were elevated, and PGF(2 alpha)-R was
      transiently affected. Such effects probably result from PGF(2 alpha) acting on
      luteal steroidogenic cells. These findings may suggest, however, that the cell
      type mediating the luteolytic actions of PGF(2 alpha), possibly the endothelium,
      could yet be nonresponsive during the early luteal phase.

PMID- 10906042
TI  - Insulin-like growth factor (IGF)-binding protein-4 proteolytic degradation in
      bovine, equine, and porcine preovulatory follicles: regulation by IGFs and
      heparin-binding domain-containing peptides.
AB  - We recently showed that insulin-like growth factor-binding protein-4 (IGFBP-4)
      proteolytic degradation in ovine preovulatory ovarian follicles is IGF-dependent
      and regulated by the heparin-binding domain (HBD) from IGFBP-3 and from
      connective tissue growth factor (CTGF), heparan/heparin-interacting protein
      (HIP), and vitronectin. The present study investigated regulation of IGFBP-4
      proteolytic degradation in porcine, bovine, and equine ovarian preovulatory
      follicles. Follicular fluid from such preovulatory follicles contains proteolytic
      activity, degrading exogenous IGFBP-4. An excess of IGF-I enhanced IGFBP-4
      degradation. In contrast, IGFBP-2 or -3 or monoclonal antibodies against IGF-I or
      -II dose-dependently inhibited IGFBP-4 degradation, and IGF-I or -II reversed
      this inhibition in a dose-dependent manner. Heparin-binding peptides derived from
      the C-terminal domain of IGFBP-3 or -5 inhibited IGFBP-4 degradation. Other
      heparin-binding peptides derived from CTGF, HIP, and vitronectin also inhibited
      IGFBP-4 degradation, except in porcine follicles. Finally, IGFBP-3 that was
      mutated in its HBD was less effective at inhibiting IGFBP-4 degradation. Thus, in
      bovine, porcine, and equine preovulatory follicles, IGFBP-4 proteolytic
      degradation both depends on IGFs and is inhibited by peptides containing HBD.
      Overall, these results suggest that during terminal development of follicles to
      the preovulatory stage in domestic animal species, the increase in IGF
      bioavailability might enhance IGFBP-4 degradation. In contrast, in atretic
      follicles, the decrease in IGF bioavailability, resulting partly from the
      increase in IGFBP-2 (sow, heifer, mare) and IGFBP-5 (heifer) expression would
      participate in the decrease of IGFBP-4 degradation. In bovine atretic follicles,
      IGFBP-5 would also strengthen the inhibition of IGFBP-4 degradation by direct
      interaction of its HBD with the protease. The involvement of other HBD-containing
      proteins in the modulation of intrafollicular proteases degrading IGFBP-4 remains
      to be investigated.

PMID- 10906043
TI  - Expression of rabbit zona pellucida-1 messenger ribonucleic acid during early
      follicular development.
AB  - Progress in research on initiation of folliculogenesis has progressed slowly
      because of a lack of markers for early folliculogenesis. The rabbit zona
      pellucida protein (ZP1) is synthesized in follicles during early stages of
      folliculogenesis. In order to establish ZP1 as a marker for initiation of
      folliculogenesis, in situ hybridization was used to localize ZP1 mRNA in immature
      follicles. ZP1 mRNA was first detected in oocytes of some but not all primordial
      follicles. The primordial follicles expressing ZP1 mRNA were located at the
      cortico-medullary junction, indicating that they were newly activated follicles.
      ZP1 mRNA accumulated in oocytes of intermediate, primary, and secondary
      follicles. In contrast, ZP1 mRNA was first detectable in granulosa cells of
      intermediate follicles and is present in cuboidal granulosa cells of primary and
      early secondary follicles, but was undetectable in granulosa cells of more mature
      follicles. These data demonstrate that 1) ZP1 mRNA is expressed in both oocytes
      and granulosa cells, 2) ZP1 mRNA is initially expressed in oocytes of activated
      follicles, and 3) ZP1 mRNA is transiently expressed in granulosa cells during
      early stages of folliculogenesis. Therefore, rabbit ZP1 is a molecular marker
      that can be used in future studies to measure initiation of folliculogenesis.

PMID- 10906044
TI  - Elimination of male germ cells in transgenic mice by the diphtheria toxin A chain
      gene directed by the histone H1t promoter.
AB  - Expression of the diphtheria toxin A-chain gene was directed to the male germ
      line by fusion to 1 kilobase of the 5'-flanking DNA of the rat histone H1t gene.
      Two independent lines of mice were established that expressed the toxic
      transgene. Female carriers were fertile; males were sterile although otherwise
      apparently normal. Adult transgenic males had very small testes that were
      virtually devoid of germ cells. A developmental study showed that germ cells
      survived until late fetal life but that testes of 3-day-old transgenic mice were
      severely depleted of prospermatogonia. During postnatal development of transgenic
      animals, remaining germ cells progressed to the pachytene stage of meiosis in 10%
      to 30% of tubular cross sections but degenerated before the completion of
      meiosis. By 3 mo of age the residual germ cells had almost completely
      disappeared. These transgenic lines demonstrate the complete tissue specificity
      of the H1t promoter and reveal a period of its activity just prior to formation
      of the definitive adult spermatogonial stem cell population. Whereas full
      expression of H1t occurs only in mid to late pachytene spermatocytes, one or more
      of the factors that impart tissue specificity to its expression must be
      transiently activated in the neonatal germ line. This report discusses the
      possibility that this genetic technique for eliminating germ cells may have
      practical application in making recipients for spermatogonial stem cell
      transplantation.

PMID- 10906045
TI  - Interferon-tau modulates phorbol ester-induced production of prostaglandin and
      expression of cyclooxygenase-2 and phospholipase-A(2) from bovine endometrial
      cells.
AB  - Antiluteolytic actions of bovine interferon-tau (bIFN-tau) require suppression of
      prostaglandin F(2 alpha) (PGF(2 alpha)) production. Our objective was to test
      whether bIFN-tau could block PGF(2 alpha) production and synthesis of
      phospholipase A(2) (PLA(2)) and cyclooxygenase-2 (COX-2) enzymes induced by a
      protein kinase C (PKC) stimulator (phorbol 12,13 dibutyrate; PDBu). Bovine
      endometrial epithelial (BEND) cells were treated with PDBu in the presence or
      absence of bIFN-tau. Medium samples were analyzed for concentrations of PGF(2
      alpha), whole-cell extracts were analyzed for abundance of PLA(2) and COX-2 by
      immunoblotting, and RNA extracts were examined for steady-state levels of COX-2
      mRNA by Northern blotting. The PDBu stimulated production of PGF(2 alpha) between
      3 and 12 h, levels of COX-2 mRNA by 3 h and protein expression of COX-2 and
      PLA(2) by 6 and 12 h, respectively. Added concomitantly with PDBu, bIFN-tau
      suppressed PGF(2 alpha) production, steady-state levels of COX-2 mRNA, and
      expression of COX-2 and PLA(2) proteins. Added after a 3-h stimulation with PDBu
      alone, bIFN-tau suppressed PGF(2 alpha) production after 1 h. Bovine IFN-tau
      inhibited intracellular mechanisms responsible for PGF(2 alpha) production in
      BEND cells, and this could be through both cytosolic and nuclear actions.

PMID- 10906046
TI  - Nitric oxide synthase inhibition in human sperm affects sperm-oocyte fusion but
      not zona pellucida binding.
AB  - There is recent evidence that mouse and human spermatozoa contain constitutive
      nitric oxide synthase (cNOS) and can synthesize nitric oxide. The aim of this
      study was to investigate whether the inhibition of human sperm cNOS could affect
      sperm-oocyte fusion and sperm binding to the zona pellucida (ZP). N(G)-nitro-L
      arginine methyl ester (L-NAME) was used as cNOS inhibitor. Sperm-oocyte fusion
      was evaluated using the hamster egg penetration test (HEPT). The ZP binding was
      evaluated using the hemizona assay. L-NAME added from the onset of capacitation
      strongly inhibited sperm-oocyte fusion. This inhibitory effect was dose
      dependent, stereospecific, and suppressed by L-arginine in a dose-dependent
      manner. L-NAME also inhibited sperm-oocyte fusion in the HEPT enhanced with
      progesterone (P), where P (5 microM) was added for 15 min to capacitated sperm. A
      lesser but significant inhibition was also observed when sperm suspensions were
      exposed to L-NAME following capacitation in both versions of HEPT. On the
      contrary, L-NAME did not affect ZP binding. In conclusion, the present study
      provides the evidence that cNOS plays a role in the human sperm's capacity to
      fuse with oocyte but not in the ZP binding.

PMID- 10906047
TI  - The human blastocyst regulates endometrial epithelial apoptosis in embryonic
      adhesion.
AB  - The implanting blastocyst must appose and adhere to the endometrial epithelium
      and, subsequently, invade it. Locally regulated uterine epithelial apoptosis
      induced by the embryo is a crucial step of the epithelial invasion in rodents. To
      address the physiological relevance of this process in humans, we investigated
      the effect of single human blastocysts on the regulation of apoptosis in cultured
      human endometrial epithelial cells (hEEC) in both apposition and adhesion phases
      of implantation. Here, we report a co-ordinated embryonic regulation of hEEC
      apoptosis. In the apposition phase, the presence of a blastocyst rescues hEEC
      from the apoptotic pathway. However, when the human blastocyst adheres to the
      hEEC monolayer, it induces a paracrine apoptotic reaction. Fas ligand (Fas-L) was
      present at the embryonic trophoectoderm. Fas was localized at the apical cell
      surface of hEEC, and flow cytometry revealed that 60% of hEEC express Fas.
      Neutralizing adhesion assays revealed that the Fas/Fas-L death system may be an
      important mechanism to cross the epithelial barrier, which is crucial for
      embryonic adhesion, and the manipulation of this system could have potential
      clinical implications as an interceptive mechanism.

PMID- 10906048
TI  - Testicular recrudescence in the male black bear (Ursus americanus): changes in
      testicular luteinizing hormone-, follicle-stimulating hormone-, and prolactin
      receptor ribonucleic acid abundance and dependency on prolactin.
AB  - Testicular recrudescence in male black bears (Ursus americanus) is initiated in
      January and completed in May. The goals of this study in the black bear were to
      determine 1) if testicular abundance of LH-receptor (LHr), FSH-receptor (FSHr),
      and prolactin-receptor (PRLr) mRNA changes during recrudescence; 2) if these
      changes in mRNA abundance are associated with changes in serum LH, PRL, and
      testosterone (T) concentrations; and 3) if the spring increase in serum PRL
      concentrations is required for testicular recrudescence. Serum was obtained
      monthly from nine male bears for 2 yr, except in July and August. To suppress
      endogenous PRL, four bears were treated with Parlodel LAR, 50 mg per 70 kg body
      weight, monthly from January through May, whereas five bears served as controls.
      Testicular biopsies were obtained in January, March, and May and analyzed for
      LHr, FSHr, and PRLr mRNA abundance using reverse transcriptase-competitive
      polymerase chain reaction. The LHr and PRLr mRNA abundance was low in January,
      increased in March, and remained high in May, whereas the FSHr mRNA abundance
      remained constant. Serum concentrations of PRL and T increased in March,
      coincident with the increase in testicular LHr and PRLr mRNA abundance.
      Suppression of serum PRL concentrations during testicular recrudescence 1)
      prevented the increase in testicular LHr and PRLr mRNA abundance observed among
      control bears in March, 2) lowered serum T concentrations in March and April, and
      3) resulted in reduced testis size in May. We conclude that testicular LHr and
      PRLr mRNA are seasonally regulated, and that PRL has a role in testicular
      recrudescence in the black bear.

PMID- 10906049
TI  - Oxytocin and vasopressin expression in the ovine testis and epididymis: changes
      with the onset of spermatogenesis.
AB  - Contractions of seminiferous tubules and epididymal duct walls promote
      spermiation and sperm transfer, and they are thought to be stimulated by the
      related peptides oxytocin and vasopressin. This study tested the hypothesis that
      if oxytocin and/or vasopressin play a physiological role in sperm shedding and
      transport, then local or circulating concentrations of these peptides would
      increase during puberty. Testes, epididymides, and trunk blood of sheep at stages
      during the first spermatogenic wave were collected, and radioimmunoassay measured
      significant increases in testicular and epididymal oxytocin during
      spermatogenesis. No changes were measured in circulating oxytocin or in local or
      circulating vasopressin. Localization and synthesis was investigated by
      immunohistochemistry and Western blot analysis employing antibodies recognizing
      epitopes of either oxytocin, oxytocin-associated neurophysin, vasopressin, or
      vasopressin-associated neurophysin. Marked expression of both oxytocin and its
      associated neurophysin in testicular Leydig and epididymal principal cells was
      seen, and weak neurophysin immunoreactivity was also identified in Sertoli cells.
      The intercellular distribution of oxytocin varied between regions of the
      epididymis, suggesting several roles for oxytocin. Vasopressin synthesis was not
      apparent in either tissue. These results confirm the presence and development of
      paracrine oxytocinergic systems in the ram testis and epididymis of ram during
      puberty while questioning the physiological importance of vasopressin.

PMID- 10906050
TI  - Interaction of extracellular matrix and activin-A in the initiation of follicle
      growth in the mouse ovary.
AB  - The precise mechanism for the initiation of follicle growth and progression
      through the earliest stages of follicle development remains largely unknown.
      Activins play a role during early follicle development, and evidence suggests
      that the extracellular matrix plays a role during later stages of follicular
      growth. We investigated the role of activin-A and extracellular matrix in
      follicle growth initiation and early follicular development in the mouse ovary.
      Ovaries were collected from 5-day-old mice and cultured for 10 days on
      polylysine, collagen, or laminin in the presence or absence of recombinant human
      activin-A. Follicle density, indices of follicle growth initiation
      (primary:primordial follicle [PY:PD] and primary:total follicle [PY:TF] ratios),
      ratios of multilayer follicle:total follicle (ML:TF), and follicle growth rates
      were compared between groups. Follicle densities were significantly higher in the
      extracellular matrix treatment group compared with the polylysine group (P <
      0.01). Also, compared with polylysine, both collagen and laminin significantly
      increased indices of follicle growth initiation (PY:PD ratio: P < 0.001, odds
      ratio of 3.3; PY:TF ratio: P < 0.001, odds ratio of 2.5), and these were not
      altered by activin treatment. In the absence of activin-A, exposure to neither
      collagen nor laminin had an effect on multilayer follicle development. When
      activin-A was added, collagen and laminin had opposing effects on multilayer
      follicle development. Activin-A stimulated multilayer follicle development in the
      presence of laminin (ML:TF ratio: P = 0.01, odds ratio of 10.8), whereas it
      suppressed follicle growth in collagen (P = 0.01). Activin-A did not affect the
      ML:TF ratio in the polylysine-treated groups. These results strongly suggest that
      extracellular matrix components and activin-A interact with each other, and that
      they regulate follicle growth initiation and multilayer follicle development.

PMID- 10906051
TI  - Mammalian sperm-egg fusion: evidence that epididymal protein DE plays a role in
      mouse gamete fusion.
AB  - Rat epididymal protein DE associates with the sperm surface during epididymal
      maturation and is a candidate molecule for mediating gamete membrane fusion in
      the rat. Here, we provide evidence supporting a role for DE in mouse sperm-egg
      fusion. Western blot studies indicated that the antibody against rat protein DE
      can recognize the mouse homologue in both epididymal tissue and sperm extracts.
      Indirect immunofluorescence studies using this antibody localized the protein on
      the dorsal region of the acrosome. Experiments in which zona-free mouse eggs were
      coincubated with mouse capacitated sperm in the presence of DE showed a
      significant and concentration-dependent inhibition in the percentage of
      penetrated eggs, with no effect on either the percentage of oocytes with bound
      sperm or the number of sperm bound per egg. Immunofluorescence experiments
      revealed specific DE-binding sites on the fusogenic region of mouse eggs. Because
      mouse sperm can penetrate zona-free rat eggs, the participation of DE in this
      interaction was also investigated. The presence of the protein during gamete
      coincubation produced a significant reduction in the percentage of penetrated
      eggs, without affecting the binding of sperm to the oolemma. These observations
      support the involvement of DE in an event subsequent to sperm-egg binding and
      leading to fusion in both homologous (mouse-mouse) and heterologous (mouse-rat)
      sperm-egg interaction. The lack of disintegrin domains in DE indicates that the
      protein interacts with its egg-binding sites through a novel mechanism that does
      not involve the reported disintegrin-integrin interaction.

PMID- 10906052
TI  - Spermatid-specific expression of the novel X-linked gene product SPAN-X localized
      to the nucleus of human spermatozoa.
AB  - Formation of mature spermatozoa involves a series of dramatic molecular and
      morphological changes in the male germ cell lineage. These changes result from
      the temporally regulated transcription and translation of several testis-specific
      gene products. Here, we describe a novel, testis-specific protein designated SPAN
      X for sperm protein associated with the nucleus on the X chromosome. SPAN-X
      sequences showed no significant similarity with known cDNA or peptide sequences.
      The SPAN-X peptide sequences contained three overlapping consensus nuclear
      localization signals, a high percentage (33%-37%) of charged amino acid residues,
      and a relatively acidic isoelectric point (pI; 4.88-6.05). Northern analysis of
      mRNA from multiple human tissues identified a SPAN-X transcript exclusively in
      the testis. In situ hybridization of human testes sections showed SPAN-X mRNA
      expression in haploid, round, and elongating spermatids. The SPANX gene was
      mapped to chromosome Xq27. 1 by fluorescence in situ hybridization and by
      Southern blot analysis of human/mouse somatic cell hybrids. On Western blots of
      human sperm proteins, antirecombinant SPAN-X antibodies reacted with broad bands
      migrating between 15-20 kDa. Immunofluorescent labeling of human spermatozoa
      demonstrated SPAN-X localization to nuclear craters and cytoplasmic droplets.
      Expression of SPAN-X, an X-linked gene product, exclusively in haploid spermatids
      leads to interesting questions regarding the transcription of sex-linked genes
      during spermiogenesis.

PMID- 10906053
TI  - Stage-specific inhibition of deoxyribonucleic acid synthesis and induction of
      apoptosis by antracyclines in cultured rat spermatogenic cells.
AB  - A rapid in vitro method has been developed to detect early effects of cytostatic
      drugs on rat spermatogenesis. The induction of programmed cell death (apoptosis)
      and changes in DNA synthesis induced by doxorubicin and idarubicin were measured
      in specific stages of the cycle of seminiferous epithelium including mitotic
      (stage V) and meiotic (stage VIII-IX) S-phase cells. The model was used to
      investigate the protective effect of an organic thiophosphate, amifostine,
      against the toxicity of antracyclines. Premitotic DNA synthesis was found to be
      more sensitive than premeiotic DNA synthesis to antracyclines. Idarubicin was
      more toxic than doxorubicin to germ cells in inducing apoptosis and suppressing
      DNA synthesis. Amifostine had no protective effect against doxorubicin- or
      idarubicin-induced inhibition of DNA synthesis. In contrast, a significant
      stimulation of DNA synthesis in premitotic cells by amifostine was found,
      suggesting that this compound may have a stimulative effect on spermatogenic stem
      cells. These data show that stage-specific dissection of the seminiferous tubules
      and their in vitro exposure to predetermined doses of drugs may give us a unique
      possibility to detect drug action and protection against the cytotoxicity of
      antineoplastic agents at the cellular level of the spermatogenic cycle.

PMID- 10906054
TI  - Mechanism of intracellular pH increase during parthenogenetic activation of In
      vitro matured porcine oocytes.
AB  - Parthenogenetic activation of porcine oocytes by using 7% ethanol, 50 or 100
      microM A23187 results in an increase in intracellular pH as does prolonged
      exposure to thimerosal. We attempt to specify which transporters or mechanisms
      are involved in the observed increase in intracellular pH during oocyte
      activation. Experiments were performed in the absence of sodium; the presence of
      2.5 mM amiloride, a potent inhibitor of the Na(+)/H(+) antiport; in the absence
      of bicarbonate; and in the presence of 4, 4'-diisothiocyanatodihydrostilbene-2,2'
      di-sulfonic acid, disodium salt (H(2)DIDS) for all three activation methods.
      These treatments had no effect on the increase in intracellular pH induced by the
      calcium ionophore or thimerosal, but all reduced the increase in pH (P < 0.001)
      in the 7% ethanol group. This suggests that the Na(+)/H(+) antiport and the
      HCO(3)(-)/Cl(-) exchangers are not playing a role during treatment with calcium
      ionophore or thimerosal, and the pH increase observed during treatment with 7%
      ethanol may be dependent upon a sodium or bicarbonate flux (or both) into the
      oocyte. Bafilomycin A1 (500 nm), an inhibitor of vacuolar-type H(+) ATPases, had
      no effect on 7% ethanol or thimerosal treatments, but significantly reduced the
      increase in intracellular pH observed during calcium ionophore treatment. This
      may be the result of an initial local increase in intracellular free calcium
      levels.

PMID- 10906055
TI  - Effects of tri-iodothyronine on testicular interstitial cells and androgen
      secretory capacity of the prepubertal Rat.
AB  - The main objective of the study was to investigate the effects of hyperthyroidism
      on the rat testis interstitium during prepuberty, which is not well understood at
      present. Male Sprague Dawley rats were injected subcutaneously daily with saline
      (controls) or tri-iodothyronine (T(3), 50 microg/kg body weight; hyperthyroids)
      from postnatal Day 1. Rats were killed at Days 5, 7, 9, 12, 16, and 21. One
      testis of each rat was used to determine LH-stimulated (100 ng/ml) testicular
      androgen secretory capacity in vitro. The other testis was used either for
      morphometric studies (n = 5) or for immunolocalization of 3 beta-hydroxysteroid
      dehydrogenase (3 beta-HSD) to identify steroidogenic cells (n = 3) and 11 beta
      hydroxysteroid dehydrogenase 1 (11 beta-HSD1) to differentially identify adult
      Leydig cells. Daily T(3) injections resulted in significant reductions in body
      and testis weights. Morphometric analysis revealed that lower testis weights in
      rats treated with T(3) were mainly the result of reductions of total volume of
      seminiferous cords/tubules. The number of interstitial mesenchymal cells (MCs)
      was lower (P < 0.05) in T(3) rats compared with age-matched controls. The number
      of fetal Leydig cells (FLCs) was not different between the two groups; however,
      FLC hypotrophy was detected in T(3) rats at Day 16 in contrast to Day 21 in
      control rats. In both groups, morphologically identifiable adult Leydig cells
      (ALCs) were observed at Day 12 and thereafter; however, the ALC number per testis
      in T(3) rats was twice as much as those of controls. Positive immunolabeling for
      3beta-HSD was first detected in MC/progenitor cells on Day 9 in rats in the T(3)
      group (cells were still spindle-shaped) and on Day 12 in rats in the control
      group. Testicular testosterone production in vitro was lower (P < 0.05) in T(3)
      rats compared with controls at each age tested and further reductions (<0.05)
      were observed in T(3) rats at Days 16 and 21. Testicular androstenedione
      production was also lower (P < 0.05) in T(3) rats at Days 5 and 7, but increased
      (P < 0.05) thereafter, than in control rats. These findings support that there
      are more newly formed ALCs in T(3) testes than in those of controls. Moreover,
      these results demonstrate that hyperthyroidism stimulates premature hypotrophy of
      FLCs and early differentiation of increased numbers of MCs to ALCs in the
      prepubertal rat testis, further supporting the view that thyroid hormone has a
      regulatory role in initiating MC differentiation into ALCs in the prepubertal rat
      testis.

PMID- 10906056
TI  - Expression of P450 side-chain cleavage (CYP11A1) and P450 17alpha-hydroxylase
      17/20 lyase (CYP17) messenger ribonucleic acid in hamster primary interstitial
      cells in vitro: differential regulation of steroidogenesis by cyclic adenosine
      monophosphate.
AB  - Interstitial cells in the neonatal hamster do not respond to LH in vitro;
      however, side-chain cleavage (CYP11A1) and 17alpha-hydroxylase (CYP17) enzyme
      proteins are expressed in these cells. The objective of the study was to evaluate
      whether the cAMP second messenger system was active in these cells and if cAMP
      upregulates the levels of CYP11A1 and CYP17 mRNA. Interstitial cells (ICs) were
      cultured for 96 h in the presence of 5% fetal bovine serum and then cultured in
      serum-free medium in the presence of LH, forskolin, or 8-Br-cAMP for 24 h. The
      accumulation of cAMP, progesterone, and androstenedione was measured by
      radioimmunoassay, whereas CYP11A1 and CYP17 mRNA levels were determined by a
      semiquantitative reverse transcription-polymerase chain reaction and Southern
      hybridization analysis. LH failed to induce either progesterone or
      androstenedione production; however, forskolin stimulated cAMP production by
      interstitial cells in a dose-dependent manner. Moreover, both forskolin and 8-Br
      cAMP significantly elevated the levels of CYP11A1 and CYP17 mRNA and induced
      progesterone synthesis by the interstitial cell monolayer. Despite the increase
      in CYP17 mRNA levels by 8-Br-cAMP, no appreciable change was noted in
      androstenedione production. These results suggest that, in vitro, a fully
      functional adenylate cyclase system is present in cultured interstitial cells of
      the neonatal hamster and that cAMP can influence the expression of CYP11A1 and
      CYP17 genes; however, cultured cells do not appear to express LH receptors that
      are functionally linked to the adenylate cyclase system. Moreover, the
      translation of CYP17 mRNA may require additional factors, which may originate
      from maturing granulosa cells.

PMID- 10906057
TI  - Leukemia inhibitory factor, leukemia inhibitory factor receptor, and glycoprotein
      130 in rhesus monkey uterus during menstrual cycle and early pregnancy.
AB  - This goal of this study was to examine immunohistochemical distribution of
      leukemia inhibitory factor (LIF), LIF receptor (LIFR), and glycoprotein (gp) 130
      in rhesus monkey uterus during the menstrual cycle and early pregnancy. Pregnancy
      rate was significantly reduced in the control group from 66.7% (12 of 18) to
      22.2% (4 of 18) with an injection of goat anti-human recombinant LIF
      immunoglobulin G into the uterine lumen on Day 8 of pregnancy. LIF was mainly
      localized in glandular and luminal epithelium. LIF immunostaining during the
      luteal phase was stronger than it was during the proliferative phase. LIF
      staining gradually increased from Day 3 of pregnancy and reached its highest
      level on Day 9. LIFR was mainly localized in the glandular and luminal
      epithelium. LIFR staining during the luteal phase was stronger than it was during
      the proliferative phase. LIFR staining began to increase from Day 3 of pregnancy
      and reached a high level on Days 9 and 11. Gp130, a signal-transducing receptor
      component of LIF, was mainly localized in the glandular epithelium. A high level
      of gp130 was found on Days 16 and 20 of menstrual cycle, and from Days 5 to 11 of
      pregnancy. These results suggest that LIF may play an important role in monkey
      implantation, as it does in mice.

PMID- 10906058
TI  - High developmental rates of vitrified bovine oocytes following parthenogenetic
      activation, in vitro fertilization, and somatic cell nuclear transfer.
AB  - Successful cryopreservation of mammalian oocytes would provide a steady source of
      materials for nuclear transfer and in vitro embryo production. Our goal was to
      develop an effective vitrification protocol to cryopreserve bovine oocytes for
      research and practice of parthenogenetic activation, in vitro fertilization, and
      nuclear transfer. Bovine oocytes matured in vitro were placed in 4% ethylene
      glycol (EG) in TCM 199 plus 20% fetal bovine serum (FBS) at 39 degrees C for 12
      15 min, and then transferred to a vitrification solution (35% EG, 5% polyvinyl
      pyrrolidone, 0.4 M trehalose in TCM 199 and 20% FBS). Oocytes were vitrified in
      microdrops on a precooled (-150 degrees C) metal surface (solid-surface
      vitrification). The vitrified microdrops were stored in liquid nitrogen and were
      either immediately thawed or were thawed after storage for 2-3 wk. Surviving
      oocytes were subjected to 1) parthenogenetic activation, 2) in vitro
      fertilization, or 3) nuclear transfer with cultured adult fibroblast cells.
      Treated oocytes were cultured in KSOM containing BSA or FBS for 9 to 10 days.
      Embryo development rates were recorded daily and morphologically high-quality
      blastocysts were cryopreserved for nuclear transfer-derived embryos at Day 7 or
      Day 8 of culture. Immediate survival of vitrified/thawed oocytes varied between
      77% and 86%. Cleavage and blastocyst development rates of vitrified oocytes
      following in vitro fertilization or activation were lower than those of the
      controls. For nuclear transfer, however, vitrified oocytes supported embryonic
      development as equally well as fresh oocytes.

PMID- 10906059
TI  - Identification of three prolactin-related hormones as markers of invasive
      trophoblasts in the rat.
AB  - An expressed-sequence tag database search has identified three rat cDNA clones in
      the prolactin/growth hormone family, including a homologue of mouse proliferin
      related protein (PRP). The encoded proteins of the two novel clones, designated
      prolactin-like proteins L (PLP-L) and M (PLP-M), are predicted to be synthesized
      as precursors of 229 and 227 amino acids, modified by N-linked glycosylation, and
      secreted as mature glycoproteins of 199 and 200 residues, respectively. Murine
      homologues to PLP-L and PLP-M were also identified. The open reading frame of rat
      PRP encodes a precursor protein of 245 amino acids and predicts a secreted 215
      amino acid glycoprotein with 81% identity to mouse PRP. All three rat mRNAs are
      expressed in the placenta, and expression is not detected in other tissues. PLP-L
      mRNA expression is observed from Days 11-20, with highest levels at Day 13;
      highest levels of PLP-M are observed from Day 11 until parturition, with peak
      levels also on Day 13; and highest levels of PRP are also observed from Day 11
      until term, with maximal expression on Day 17. All three genes are most highly
      expressed in invasive trophoblast cells lining the central placental vessel. The
      identification of molecular markers for endovascular trophoblasts serves to
      highlight the invasive nature of rodent placentation and may prove useful for
      future studies of placental function.

PMID- 10906060
TI  - Determination of seasonality in southern hairy-nosed wombats (Lasiorhinus
      latifrons) by analysis of fecal androgens.
AB  - Little is known about the reproductive biology of Australia's critically
      endangered northern hairy-nosed wombat (Lasiorhinus krefftii), largely due to its
      cryptic nature and the difficulty in accessing the small remaining population of
      about 70 animals. Using the noninvasive technique of fecal steroid analysis, we
      have examined the endocrinology of the more common yet closely related southern
      hairy-nosed wombat (Lasiorhinus latifrons). The aims of this study were to 1)
      develop and validate fecal androgen analysis in this species, 2) examine and
      compare seasonal differences in fecal and plasma androgens in male wombats, and
      3) correlate seasonal differences in androgens with changes in male accessory
      glands (prostate and bulbourethral gland). Fecal androgens were extracted in
      ether; concentrated; separated by HPLC into testosterone (T), dihydrotestosterone
      (DHT), and 5 alpha-androstane-3 alpha,17 beta-diol (Adiol) fractions; and
      quantitated by RIA. The concentrations of androgens in fecal pellets from 14 wild
      southern hairy-nosed wombats as determined by RIA varied over the range 6.6-25.0
      ng/g dry weight for T, 4.0-24.2 ng/g dry weight for DHT, and 0-34.8 ng/g dry
      weight for Adiol. For each androgen, a highly significant linear correlation was
      observed between plasma and fecal concentrations. When individuals were grouped
      into either breeding season (pellets collected between August-November) or
      nonbreeding season (collected between February-April), significant (P < 0.05)
      differences between seasons were observed for both plasma and fecal T, plasma
      DHT, and fecal Adiol. For all androgens, the mean fecal and plasma concentrations
      were higher during the breeding season than the nonbreeding season. A significant
      (P < 0.001) correlation was observed between fecal T and prostate weight, while
      DHT and Adiol correlations were nonsignificant. Significant correlations were
      observed, however, between all three fecal androgens and bulbourethral gland
      weight. These studies demonstrate that fecal T is a valid indicator of
      reproductive status in the male southern hairy-nosed wombat, with significant
      correlations observed between fecal T, plasma T, and prostate and bulbourethral
      gland weights. These findings have important implications for the study of the
      reproductive endocrinology of the critically endangered northern hairy-nosed
      wombat.

PMID- 10906061
TI  - Differential expression of inositol 1,4,5-trisphosphate receptor types 1, 2, and
      3 in rat myometrium and endometrium during gestation.
AB  - The regulation of the phospholipase C (PLC) and the expression of inositol 1,4,5
      trisphosphate receptors (IP(3)Rs) in terms of mRNA, proteins, and binding
      capacity were examined in the rat myometrium and endometrium at midgestation (Day
      12) and at term (Day 21) comparatively to the estrogen-treated tissues (Day 0).
      In both uterine tissues, the production of inositol phosphates mediated by
      carbachol as well as by AlF(4)(-) was enhanced with advancing gestation.
      (3)[H]IP(3) binding sites in membranes also increased during pregnancy (Day 21 >
      Day 12 > Day 0). The mRNAs encoding for three isoforms of IP(3)R as well as their
      corresponding proteins, IP(3)R-1, IP(3)R-2, and IP(3)R-3 were coexpressed, albeit
      to different extents, in the myometrium and endometrium. The expression of
      IP(3)Rs increased with advancing gestation, except for IP(3)R-2 that increased
      only in the endometrium at term. Thus, the pregnancy-related upregulation of the
      PLC cascade coincided with an increase in the expression of IP(3)Rs. The
      difference noted between the two uterine tissues suggests that IP(3)Rs may have
      cell-specific functions.

PMID- 10906062
TI  - Reproductive, neuroendocrine, and immune consequences of acute exposure to
      2,3,7,8-tetrachlorodibenzo-p-dioxin in the Siberian hamster.
AB  - The present study tested the hypothesis that acute treatment with 2, 3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) impairs fertility, disrupts the nocturnal
      melatonin rhythm, and suppresses lymphocyte function. Adult Siberian hamsters
      administered 2 or 100 microg TCDD/kg body weight/0.2 ml sesame oil had a delayed
      latency to first litter and an increased adult mortality compared to hamsters
      given 0.1 microg/kg or vehicle. Within 75 days of TCDD treatment, full
      reproductive capabilities were achieved. Moreover, the nocturnal melatonin rhythm
      was not disrupted in adults administered TCDD or in their progeny. Lymphocyte
      activity varied with respect to time of day and treatment. Lymphocyte
      proliferation was enhanced at night irrespective of TCDD treatment; during the
      day, 2 wk after the 2-microg/kg treatment, blastogenesis was reduced compared to
      that in the 0.1-microg/kg group or in vehicle-treated controls. In contrast, TCDD
      did not affect the mixed lymphocyte reaction in response to allogeneic antigen
      when assessed at 2 and 20 wk post-treatment. Thus, findings indicate that TCDD
      produced acute effects on fertility, mortality, and systemic lymphocyte
      proliferation, but long-lasting effects on specific aspects of reproductive,
      neuroendocrine, and immune cell functions were not observed.

PMID- 10906063
TI  - Retinoid modulation of plasminogen activator production in rat Sertoli cells.
AB  - Tissue type (t) and urokinase type (u) plasminogen activators (PAs) have been
      shown to be secreted by Sertoli cells in the seminiferous tubules in a cyclic
      fashion and to be dependent upon FSH stimulation or upon the presence of adjacent
      spermatogenic cells. In the present study we have analyzed the production of PAs
      by retinoid-treated rat Sertoli cells. In addition, because retinoids modulate
      the response of Sertoli cells to FSH either potentiating or antagonizing its
      action, we have investigated a possible modulation of FSH-stimulated PA
      production. Under basal conditions, Sertoli cells, isolated from prepubertal
      rats, secrete predominantly uPA. A significant dose-dependent inhibition of uPA
      activity was observed after treatment with retinol, while no significant effect
      was detected upon tPA secretion. When Sertoli cells were cultured in the presence
      of 0.25 microM retinol, a significant inhibition of uPA activity was evident
      after 16 h of treatment and reached approximately 80% after 48 h of treatment.
      The analysis of the mRNA levels revealed that retinol induces an inhibition of
      the steady-state levels of uPA mRNA without affecting those of tPA. Moreover,
      retinol affected uPA mRNA levels by increasing mRNA turnover. The effect of
      retinoids on Sertoli cells isolated from older animals was less evident, possibly
      due to the reduced production of uPA with the increase of age of the donor
      animals. Our results on the effect of retinoids upon Sertoli cell uPA production
      reinforce the importance of retinoids in the control of postnatal testis
      development.

PMID- 10906064
TI  - Microgravity and hypergravity effects on fertilization of the salamander
      Pleurodeles waltl (urodele amphibian).
AB  - Effects of microgravity (microG) on fertilization were studied in the urodele
      amphibian Pleurodeles waltl on board the MIR space station. Genetic and
      cytomorphologic analyses ruled out parthenogenesis or gynogenesis and proved that
      fertilization did occur in microG. Actual fertilization was demonstrated by the
      analysis of the distribution of peptidase-1 genes, a polymorphic sex-linked
      enzyme, in progenies obtained in microG. Further evidence of fertilization was
      provided by the presence of spermatozoa in the perivitelline space and in the
      fertilization layer of the microG eggs and by the presence of a female pronucleus
      and male pronuclei in the egg cytoplasm. Experiments in microG and in 1.4G, 2G,
      and 3G hypergravity showed for the first time that, compared to eggs in 1G,
      several characteristics of the fertilization process including the cortical
      reaction and the microvillus transformations were altered depending on the
      gravitational force applied to the eggs. Microvillus elevation, the most evident
      feature, was reduced on microG-eggs and amplified on eggs submitted to 2G and 3G.
      No lethal consequences of these alterations on the early development of microG
      eggs were observed.

PMID- 10906065
TI  - Expression, ontogeny, and regulation of hypoxia-inducible transcription factors
      in the human placenta.
AB  - Placental hypoxia likely plays an important role in both normal placental
      development and pathology. Yet, the molecular mechanisms of hypoxia signaling in
      this organ are virtually unexplored. Therefore, we investigated the expression of
      the hypoxia inducible transcription factors (HIF) in normal human placentas
      spanning the first trimester to term. Several key observations emerged: 1) HIF-1
      alpha and -2 alpha mRNA were present in placentas of all gestational ages but
      with greater variability during early pregnancy; 2) overall, HIF-1 alpha mRNA was
      expressed at a constant level in all placentas, whereas HIF-2 alpha mRNA
      increased significantly with gestational age; 3) both HIF-1 alpha and -2 alpha
      protein decreased significantly with gestational age; and 4) HIF-1 alpha and -2
      alpha immunoreactivity were overlapping in cellular distribution being expressed
      by the syncytiotrophoblast, villous cytotrophoblast, and fetoplacental
      vasculature with both nuclear and cytoplasmic localization. Next, we studied the
      regulation of these transcription factors by oxygen using placental villous
      explants in culture from first-trimester and term placentas. The major findings
      were 1) HIF-1 alpha and -2 alpha protein, but not mRNA, was induced by hypoxia in
      the placental villous explants; 2) HIF-1 alpha DNA-binding activity was also
      stimulated by hypoxia; and 3) glucose transporter-1 mRNA (a known target of HIF)
      was also increased by hypoxia in placental villous explants. We suggest that
      physiological hypoxia contributes to the increased expression of HIF-1 alpha and 
      2 alpha protein in early placentas and that regulation of these transcription
      factors by hypoxia in the human placenta occurs at the level of protein and not
      mRNA.

PMID- 10906066
TI  - GATA-2 restricts prolactin-like protein A expression to secondary trophoblast
      giant cells in the mouse.
AB  - An analysis of the pattern of expression of the mouse placental hormone prolactin
      like protein A (PLP-A) has revealed that this hormone is expressed exclusively in
      secondary trophoblast giant cells but not in primary giant cells. Thus, PLP-A
      serves as a marker for a subset of giant cells. Recent results have indicated
      that PLP-A binds to and inhibits the activity of natural killer cells, and thus,
      the localized expression of PLP-A may be important for regulating the activity of
      this class of T lymphocytes in a restricted region of the implantation site.
      Previous studies indicated that the transcription factor GATA-2 is required for
      the trophoblast giant cell-specific expression of two other hormones in the
      prolactin family, placental lactogen I and proliferin. In the absence of GATA-2,
      PLP-A continues to be expressed, but in this mutant background, PLP-A mRNA is
      detected in both primary and secondary giant cells. Thus, GATA-2 contributes both
      to positive and negative regulation of trophoblast giant cell-specific gene
      expression, and this factor apparently plays an important role in generating or
      maintaining the distinct functions of secondary, compared with primary,
      trophoblast giant cells.

PMID- 10906067
TI  - A monoclonal antibody that recognizes mammalian cortical granules and a 32
      kilodalton protein in mouse eggs.
AB  - The fertilization-induced exocytosis of egg cortical granules (CGs) is
      responsible for a block to polyspermy, crucial to the viability of many species.
      The contents of mammalian CGs have been an elusive target for analysis because of
      picogram quantities of CG proteins. By using media enriched in secreted CG
      contents from calcium ionophore-induced eggs as an immunogen, a monoclonal
      antibody was raised that immunolocalized to structures in the mouse egg cortex
      with all the hallmarks of CGs. These structures were the correct size, absent
      from the region over the metaphase II spindle, and greatly reduced after
      fertilization. Double-labeling experiments confirmed that the antibody recognized
      the same population of CGs as those recognized by Lens culinaris agglutinin. On
      Western blots, the antibody primarily recognized a 32-kDa protein (and
      secondarily one at approximately 25 kDa) in mouse eggs. Analysis of biotin
      labeled secreted proteins from activated eggs confirmed that CGs release only a
      small number of major proteins (45, 34, 32, 28, and approximately 20 kDa by SDS
      PAGE). We therefore propose that the 32-kDa protein identified by this antibody
      is likely to correspond to the 32-kDa protein released from activated eggs and
      that it may be involved in the block to polyspermy. These methods should make it
      possible to generate additional antibodies to study the structure of CG
      components as well as their roles in the polyspermy block and CG biogenesis.

PMID- 10906068
TI  - Ubiquitinated sperm mitochondria, selective proteolysis, and the regulation of
      mitochondrial inheritance in mammalian embryos.
AB  - The strictly maternal inheritance of mitochondria and mitochondrial DNA (mtDNA)
      in mammals is a developmental paradox promoted by an unknown mechanism
      responsible for the destruction of the sperm mitochondria shortly after
      fertilization. We have recently reported that the sperm mitochondria are
      ubiquitinated inside the oocyte cytoplasm and later subjected to proteolysis
      during preimplantation development (P. Sutovsky et al., Nature 1999; 402:371
      372). Here, we provide further evidence for this process by showing that the
      proteolytic destruction of bull sperm mitochondria inside cow egg cytoplasm
      depends upon the activity of the universal proteolytic marker, ubiquitin, and the
      lysosomal apparatus of the egg. Binding of ubiquitin to sperm mitochondria was
      visualized by monospecific antibodies throughout pronuclear development and
      during the first embryonic divisions. The recognition and disposal of the
      ubiquitinated sperm mitochondria was prevented by the microinjection of anti
      ubiquitin antibodies and by the treatment of the fertilized zygotes with
      lysosomotropic agent ammonium chloride. The postfecundal ubiquitination of sperm
      mitochondria and their destruction was not seen in the hybrid embryos created
      using cow eggs and sperm of wild cattle, gaur, thus supporting the hypothesis
      that sperm mitochondrion destruction is species specific. The initial ligation of
      ubiquitin molecules to sperm mitochondrial membrane proteins, one of which could
      be prohibitin, occurs during spermatogenesis. Even though the ubiquitin cross
      reactivity was transiently lost from the sperm mitochondria during epididymal
      passage, likely as a result of disulfide bond cross-linking, it was restored and
      amplified after fertilization. Ubiquitination therefore may represent a mechanism
      for the elimination of paternal mitochondria during fertilization. Our data have
      important implications for anthropology, treatment of mitochondrial disorders,
      and for the new methods of assisted procreation, such as cloning, oocyte
      cytoplasm donation, and intracytoplasmic sperm injection.

PMID- 10906069
TI  - Telomere length in male germ cells is inversely correlated with telomerase
      activity.
AB  - Telomeres, the noncoding sequences at the ends of chromosomes, progressively
      shorten with each cellular division. Spermatozoa have very long telomeres but
      they lack telomerase enzymatic activity that is necessary for de novo synthesis
      and addition of telomeres. We performed a telomere restriction fragment analysis
      to compare the telomere lengths in immature rat testis (containing type A
      spermatogonia) with adult rat testis (containing more differentiated germ cells).
      Mean telomere length in the immature testis was significantly shorter in
      comparison to adult testis, suggesting that type A spermatogonia probably have
      shorter telomeres than more differentiated germ cells. Then, we isolated type A
      spermatogonia from immature testis, and pachytene spermatocytes and round
      spermatids from adult testis. Pachytene spermatocytes exhibited longer telomeres
      compared to type A spermatogonia. Surprisingly, although statistically not
      significant, round spermatids showed a decrease in telomere length. Epididymal
      spermatozoa exhibited the longest mean telomere length. In marked contrast,
      telomerase activity, measured by the telomeric repeat amplification protocol was
      very high in type A spermatogonia, decreased in pachytene spermatocytes and round
      spermatids, and was totally absent in epididymal spermatozoa. In summary, these
      results indicate that telomere length increases during the development of male
      germ cells from spermatogonia to spermatozoa and is inversely correlated with the
      expression of telomerase activity.

PMID- 10906070
TI  - Cadmium inhibits vacuolar H(+)ATPase-mediated acidification in the rat
      epididymis.
AB  - In rats, an acidic luminal pH maintains sperm quiescence during storage in the
      epididymis. We recently showed that vacuolar H(+)ATPase-rich cells in the
      epididymis and vas deferens are involved in the acidification of these segments.
      Treatment of rats with cadmium (Cd) leads to alkalinization of this fluid by an
      unknown mechanism. Because Cd may affect H(+)ATPase function, we examined 1) the
      in vivo effect of Cd poisoning on H(+)ATPase-rich cell morphology and on the
      abundance and distribution of the 31-kDa H(+)ATPase subunit in cells along the
      rat epididymis, and 2) the in vitro effect of Cd on H(+)ATPase activity and
      function in the isolated vas deferens. Immunofluorescence and immunoblotting data
      from rats treated with Cd for 14-15 days (2 mg Cd/kg body mass/day) showed that
      1) H(+)ATPase-positive cells regressed to a prepubertal phenotype, and 2)
      H(+)ATPase was lost from the apical pole of the cell and was redistributed into
      an intracellular compartment. In experiments in vitro, Cd inhibited bafilomycin
      sensitive ATPase activity in isolated total cell membranes and, as measured using
      a proton-selective extracellular microelectrode, inhibited proton secretion in
      isolated vas deferens. We conclude that alkalinization of the tubule fluid in the
      epididymis and vas deferens of Cd-treated rats may result from the loss of
      functional H(+)ATPase enzyme in the cell apical domain as well as from a direct
      inhibition of H(+)ATPase function by Cd.

PMID- 10906071
TI  - A novel isoform of human cyclic 3',5'-adenosine monophosphate-dependent protein
      kinase, c alpha-s, localizes to sperm midpiece.
AB  - Using rapid amplification of cDNA ends, a cDNA encoding a novel splice variant of
      the human C alpha catalytic subunit of cAMP-dependent protein kinase (PKA) was
      identified. The novel isoform differed only in the N-terminal part of the deduced
      amino acid sequence, corresponding to the part encoded by exon 1 in the
      previously characterized murine C alpha gene. Sequence comparison revealed
      similarity to an ovine C alpha variant characterized by protein purification and
      micropeptide sequencing, C alpha-s, identifying the cloned human cDNA as the C
      alpha-s isoform. The C alpha-s mRNA was expressed exclusively in human testis and
      expression in isolated human pachytene spermatocytes was demonstrated. The C
      alpha-s protein was present in ejaculated human sperm, and immunofluorescent
      labeling with a C alpha-s-specific antibody indicated that C alpha-s was
      localized in the midpiece region of the spermatozoon. The majority of C alpha-s
      was particulate and could not be released from the sperm midpiece by cAMP
      treatment alone. Furthermore, detergent extraction solubilized approximately two
      thirds of the C alpha-s pool, indicating interaction both with detergent
      resistant cytoskeletal and membrane structures. In addition, we recently
      identified the regulatory subunit isoforms RI alpha, RII alpha, and an A-kinase
      anchoring protein, hAKAP220 in this region in sperm that could target C alpha-s.
      This novel C alpha-s splice variant appeared to have an independent anchor in the
      human sperm midpiece as it could not be completely solubilized even in the
      presence of both detergent and cAMP.

PMID- 10906072
TI  - The cause of infertility of male c-ros tyrosine kinase receptor knockout mice.
AB  - Male homozygous transgenic c-ros knockout mice are sterile by natural mating,
      lack a part of their epididymis, and the epididymal sperm exhibit tail angulation
      in vivo and in vitro. To ascertain if this abnormal tail form caused the
      infertility, the number and nature of sperm in the tract of females mated to
      knockout and wild-type mice were determined. Percentage motility and numbers of
      sperm in the uterus 1 h after mating were similar between genotypes. The majority
      of the uterine sperm from the wild-type males had straight flagella, whereas 46
      86% of knockout sperm were bent at the cytoplasmic droplet even when motile.
      Motile knockout sperm showed a 54 and 37% reduction in the straightline and
      curvilinear velocities compared with straight wild-type sperm. Sequential
      flushings of the oviduct 4 h after mating with the wild-type males contained
      sperm: 591 +/- 119 free, 371 +/- 70 loosely, and 122 +/- 47 tightly bound to the
      epithelium, but no knockout sperm were recovered from the oviduct or observed
      within the uterotubal junction in tissue sections. The infertility of c-ros
      knockout male mice can be explained by the sperm's inability to enter the
      oviduct, as a result of their bent tails forming the entangled sperm mass and
      their compromised flagellar vigor within the uterus.

PMID- 10906074
TI  - Protein composition of the ventral processes on the sperm head of Australian
      hydromyine rodents.
AB  - The sperm head of the plains rat, an Australian hydromyine rodent, is highly
      complex in structure and contains, in addition to an apical hook, two large
      ventral processes (VPs) that extend from its upper concave surface and that are
      largely composed of a huge extension of the sperm head cytoskeleton surrounded by
      postacrosomal dense lamina. In this study we have attempted to determine their
      protein composition. For this, the VPs were isolated, the proteins within them
      separated by SDS-PAGE, and the resultant polypeptide bands Western blotted and
      probed with antibodies against laboratory rat perforatorial and bull perinuclear
      theca sperm proteins. Antibodies were also used to determine the perforatorial
      and perinuclear theca proteins by immunogold labeling of transmission electron
      microscopic sections. The results indicate that the material within the VPs is
      largely composed of perforatorial cross-reacting proteins together with F-actin
      with the dominant protein being PERF 15. The perinuclear theca proteins are, by
      contrast, restricted to a narrow region adjacent to the acrosomal and nuclear
      membranes. In conclusion, this study has shown that the VPs of the spermatozoa of
      Australian rodents are perforatorial-like appendages that contain similar
      proteins to the perforatorium of the apical hook together with F-actin; their
      functional significance remains unknown.

PMID- 10906073
TI  - Production, purification, and carboxy-terminal sequencing of bioactive
      recombinant bovine interferon-stimulated gene product 17.
AB  - An interferon (IFN)-stimulated gene (ISG) encodes a bovine 17-kDa protein
      (bISG17) that is released from endometrial cells but also conjugates to
      intracellular proteins through a ubiquitinlike mechanism. During early pregnancy
      in ruminants, conceptus-derived IFN-tau induces endometrial ISG17. The present
      experiments were designed to generate bioactive recombinant (r) bISG17. The
      Pichia pastoris yeast expression system was used because previous experiments
      expressing the human ISG15 ortholog in bacteria were confounded by inherent
      carboxypeptidase activity that cleaved C-terminal residues resulting in an
      inactive protein. In a series of extensive yeast culture experiments using shaker
      bath and fermentation approaches, optimal conditions were determined for a
      transformant containing a multi-ISG17 gene insertion. Recombinant bISG17 was
      purified. Carboxy-terminal sequencing revealed that rbISG17 retained the C
      terminal Gly that is potentially critical for the first step in covalent
      attachment to targeted intracellular proteins. The rISG17 induced (P < 0.0001)
      IFN-gamma mRNA (reverse transcription-polymerase chain reaction) and release of
      IFN-gamma protein (ELISA) by bovine peripheral blood mononuclear cells. The IFN
      gamma mRNA also was upregulated (P < 0.0001) in endometrium from pregnant (Day
      18) when compared with nonpregnant (Days 14 and 18) cows. It is concluded that
      rbISG17 generated in a yeast expression system retains cytokine/hormonal
      activity. This is the first description coupling the biology of two distinct IFNs
      (gamma and tau) through the intermediary ubiquitin homolog ISG17.

PMID- 10906075
TI  - Gonadotropin-releasing hormone-stimulated sperm binding to the human zona is
      mediated by a calcium influx.
AB  - The mechanism by which GnRH increases sperm-zona pellucida binding in humans was
      investigated in this study. We tested whether GnRH increases sperm-zona binding
      in Ca(2+)-free medium and in the presence of Ca(2+) channel antagonists. We also
      examined the GnRH effect on the intracellular free Ca(2+) concentration
      ([Ca(2+)](i)). Sperm treatment with GnRH increased sperm-zona binding 300% but
      only when Ca(2+) was present in the medium. In Ca(2+)-free medium or in the
      presence of 400 nM nifedipine, 80 microM diltiazem, or 50 microM verapamil, GnRH
      did not influence sperm-zona binding. GnRH increased the [Ca(2+)](i) in the sperm
      in a dose-dependent manner. The maximum effect was reached with 75 nM GnRH. The
      GnRH-induced increase in [Ca(2+)](i) was fast and transient, from a basal
      [Ca(2+)](i) of 413 +/- 22 nM to a peak value of 797 +/- 24 nM. The GnRH-induced
      increase in [Ca(2+)](i) was entirely due to a Ca(2+) influx from the
      extracellular medium because the increase in [Ca(2+)](i) was blocked by the
      Ca(2+) chelator EGTA and by the Ca(2+) channel antagonists nifedipine and
      diltiazem. These antagonists, however, were not able to inhibit the progesterone
      activated Ca(2+) influx. On the contrary, T-type calcium channel antagonists
      pimozide and mibefradil did not affect GnRH-activated Ca(2+) influx but inhibited
      the progesterone-activated Ca(2+) influx. Finally, the GnRH-induced Ca(2+) influx
      was blocked by two specific GnRH antagonists, Ac-D-Nal(1)-Cl-D-Phe(2)-3-Pyr-D
      Ala(3)-Arg(5)-D-Glu(AA)(6)-GnRH and Ac-(3,4)-dehydro-Pro(1),-p-fluoro-D-Phe(2), D
      Trp(3,6)-GnRH. These results suggest that GnRH increases sperm-zona binding via
      an elevation of [Ca(2+)](i) through T-type, voltage-operated calcium channels.

PMID- 10906076
TI  - Synaptosome-associated protein of 25 kilodaltons in oocytes and steroid-producing
      cells of rat and human ovary: molecular analysis and regulation by gonadotropins.
AB  - The synaptosome-associated protein of 25 kDa (SNAP-25) is crucially involved in
      exocytosis in neurons. The aim of this study was to investigate whether it is
      present in the ovary. We found SNAP-25 to be expressed in nonneuronal cells of
      the rat and human ovary, namely in all oocytes and in steroidogenic cells,
      including granulosa cells (GC) of large antral follicles and luteal cells. Both
      isoforms, SNAP-25a and b, were found in the ovary. Oocytes obtained by laser
      capture microdissection were shown to express SNAP-25b, whereas SNAP-25a was
      found in rat GC and human luteinized GC. Immunohistochemical observations of
      strong SNAP-25 staining in GC of large growing antral follicles compared with
      absent or weak staining in small follicles suggested a role in folliculogenesis.
      To study a presumed regulation of SNAP-25, we used a rat GC line (GFSHR-17),
      which expresses FSH receptors, and luteinizing human GC, which express LH
      receptors. FSH elevated SNAP-25 mRNA and protein levels about fivefold within 24
      h in GFSHR-17 cells. The cAMP analogue dibutyryl-cAMP (db-cAMP) mimicked this
      action of FSH. The effects of both db-cAMP and FSH were inhibited by the protein
      kinase A (PKA) inhibitor H89. In contrast, SNAP-25 protein and mRNA-levels were
      not altered by LH/hCG in luteinized human GC. Our results for the first time
      identify SNAP-25b in oocytes and SNAP-25a in steroidogenic cells of the mammalian
      ovary. SNAP-25a and b may be involved in different exocytotic processes in these
      cell types.

PMID- 10906077
TI  - Generation of cyclic guanosine monophosphate by heme oxygenases in the human
      testis--a regulatory role for carbon monoxide in Sertoli cells?
AB  - Previous studies have demonstrated that cGMP is produced by nitric oxide-mediated
      activation of soluble guanylyl cyclase (sGC) in seminiferous tubules of the human
      testis. It is not known, however, whether carbon monoxide (CO), another activator
      of sGC, is also involved in testicular function. To address this issue,
      testicular probes from 65- to 75-yr-old men have been examined. The CO-generating
      enzyme, heme oxygenase-1 (HO-1), could be localized by immunohistochemical and
      immunoblot analyses to Sertoli cells. In these cells, HO-1 is detectable in
      adluminal cell compartments, whereas sGC immunoreactivity is distributed
      exclusively in basal compartments. Treatments of isolated tubules with either
      sodium arsenite, known to induce HO-1, or hematin, an HO substrate, resulted in
      4.4- and 1.8-fold, respectively, increases in cGMP levels. ODQ, a specific sGC
      inhibitor, inhibited completely the sodium arsenite-stimulated cGMP production.
      Moreover, the HO inhibitor zinc protoporphyrin-IX and the CO scavenger hemoglobin
      both significantly reduced (77% or 46% of control, respectively) tubular cGMP
      generation. These findings, demonstrating for the first time a link between HO-1
      activity in Sertoli cells and sGC-dependent cGMP production in seminiferous
      tubules, suggest a functional role of CO in the human testis.

PMID- 10906078
TI  - A role for the MEK-MAPK pathway in okadaic acid-induced meiotic resumption of
      incompetent growing mouse oocytes.
AB  - Fully grown competent mouse oocytes spontaneously resume meiosis in vitro when
      released from their follicular environment, in contrast to growing incompetent
      oocytes, which remain blocked in prophase I. The cell cycle regulators,
      maturation promoting factor (MPF; [p34(cdc2)/cyclin B kinase]) and mitogen
      activated protein (MAP) kinases (p42(MAPK) and p44(MAPK)), are implicated in
      meiotic competence acquisition. Incompetent oocytes contain levels of p42(MAPK),
      p44(MAPK), and cyclin B proteins that are comparable to those in competent
      oocytes, but their level of p34(cdc2) is markedly lower. Okadaic acid (OA), an
      inhibitor of phosphatases 1 and 2A, induces meiotic resumption of incompetent
      oocytes. The kinetics and the percentage of germinal vesicle breakdown depends on
      whether or not oocytes have been cultured before OA treatment. We show that the
      fast kinetics and the high percentage of germinal vesicle breakdown induced by OA
      following 2 days in culture is neither the result of an accumulation of p34(cdc2)
      protein, nor to the activation of MPF in incompetent oocytes, but rather by the
      premature activation of MAP kinases. Indeed, a specific inhibitor of MAPK kinase
      (MEK) activity, PD98059, inhibits activation of MAP kinases and meiotic
      resumption. Altogether, these results indicate that the MEK-MAPK pathway is
      implicated in OA-induced meiotic resumption of incompetent mouse oocytes, and
      that the MEK-MAPK pathway can induce meiotic resumption in the absence of MPF
      activation.

PMID- 10906079
TI  - Leprosy--a new look at an old disease.

PMID- 10906081
TI  - New online features at the eBJO

PMID- 10906080
TI  - Entry site neovascularisation after diabetic vitrectomy.

PMID- 10906082
TI  - Corneal transplantation: how successful are we?

PMID- 10906083
TI  - Progression of eye disease in "cured" leprosy patients: implications for
      understanding the pathophysiology of ocular disease and for addressing eyecare
      needs.
AB  - BACKGROUND: Ocular damage in leprosy is due either to nerve damage or
      infiltration by mycobacteria. There is currently little information about the
      magnitude and nature of incident ocular pathology in cured leprosy patients. This
      information would increase our understanding of the pathophysiology of ocular
      involvement in leprosy and help in developing programmes to address the eyecare
      needs of leprosy patients who have been released from treatment. The cumulative
      incidence of leprosy related ocular pathology and cataract was measured during an
      11 year follow up period in cured leprosy patients released from treatment in
      Korea. METHODS: In 1988 standardised eye examinations were performed on 501
      patients in eight resettlement villages in central South Korea. In May 1999
      standardised eye examinations were repeated in this population. RESULTS: Among
      the patients in whom there was no sight threatening leprosy related ocular
      disease (lagophthalmos, posterior synechia, or keratitis) in 1988, 14.7%
      developed one or more of these conditions. Overall, among those with no vision
      reducing cataract in 1988, 26.4% had developed a vision reducing lens opacity in
      at least one eye. Among patients examined in both 1988 and 1999, 14.3% developed
      visual impairment and 5.7% developed blindness. CONCLUSION: This study
      demonstrates that leprosy related ocular pathology progresses in some patients
      even after they are cured mycobiologically. The progressive leprosy related
      lesions are the result of chronic nerve damage; ocular lesions due to
      infiltration by Mycobacterium leprae did not develop. Based on the factors found
      to be associated with development of the most visually significant findings
      (posterior synechia, keratitis, and cataract) certain patients should be targeted
      at discharge for active follow up eye care. We suggest that patients with
      lagophthalmos (even in gentle closure), trichiasis, small pupils, and posterior
      synechiae should be screened regularly for the development of lagophthalmos in
      forced closure, keratitis, and cataract.

PMID- 10906084
TI  - Fibrovascular ingrowth and recurrent haemorrhage following diabetic vitrectomy.
AB  - AIM: To investigate the prevalence and the outcome of management of fibrovascular
      ingrowth (FVI) in eyes undergoing vitreous cavity washout (VCWO) following
      vitrectomy for diabetic retinopathy. METHOD: FVI was searched for at VCWO for in
      19 consecutive eyes with proliferative diabetic retinopathy undergoing vitreous
      surgery for recurrent vitreous cavity haemorrhage over an 18 month period; the
      findings were correlated with the presence or absence of associated sclerotomy
      vessels externally. Eyes with richly vascularised ingrowths from the pars plana
      entry sites, as well as eyes with less extensive ingrowths but extensive retinal
      ablation applied at previous surgery for recurrent haemorrhage, underwent
      lensectomy and ciliary membrane dissection in addition to extensive retinopexy
      (n=6). Less severe cases received peripheral laser and cryotherapy only. The
      outcome of repeat surgery was studied prospectively in the 11 eyes with FVI.
      RESULTS: 11 of the 19 eyes had a definite FVI from one or more of the original
      pars plana sclerotomies. In six of 11 eyes with FVI a large external episcleral
      vessel was present entering the original sclerotomy sites at which ingrowth was
      found peroperatively, but such sclerotomy vessels were also present in three of
      eight eyes with no FVI detected on the internal aspect of the sclerotomy. Two
      patients were lost to follow up and the remaining nine patients with FVI had no
      further vitreous cavity haemorrhage during initial follow up of 2-5 months.
      CONCLUSIONS: FVI has until now been considered an infrequent occurrence following
      vitrectomy for diabetic retinopathy. These findings would suggest that it is not
      uncommon and careful examination of the sclerotomy sites should be undertaken in
      all cases with recurrent haemorrhage and if FVI is found this should be treated
      appropriately.

PMID- 10906085
TI  - Amniotic membrane transplantation for severe neurotrophic corneal ulcers.
AB  - AIMS: To evaluate whether amniotic membrane transplantation can be an effective
      alternative treatment for neurotrophic corneal ulcers. METHODS: Amniotic membrane
      transplantation was performed in 16 eyes of 15 patients with neurotrophic corneal
      ulcers and vision equal to or worse than 20/200. The neurotrophic state was
      developed following keratoplasty (four eyes), herpes zoster ophthalmicus (four
      eyes), diabetes mellitus (four eyes), radiation (two eyes), removal of acoustic
      neuroma with neuroparalysis (one eye), and herpes simplex keratitis (one eye).
      RESULTS: During a mean follow up period of 18.8 (SD 13.0) months, one to three
      layers of amniotic membrane with or without additional membrane as a patch were
      used for 17 procedures in 16 eyes for persistent neurotrophic corneal ulcers. All
      but four (76.4%) instances of amniotic membrane transplantation achieved rapid
      epithelialisation in 16.6 (9.0) days. Of the four eyes showing delayed healing,
      three eyes healed by tarsorrhaphy, and the remaining one eye with corneal
      perforation required penetrating keratoplasty and tarsorrhaphy. Two eyes gained
      vision better than 20/200. The healed corneal surface was accompanied by reduced
      inflammation. CONCLUSION: Amniotic membrane transplantation can be considered an
      effective alternative for treating severe neurotrophic corneal ulcers.

PMID- 10906086
TI  - Atopy and keratoconus: a multivariate analysis.
AB  - BACKGROUND/AIMS: The primary goal of this study was to determine if atopy is a
      risk factor for keratoconus. Other potential risk factors were also studied and
      included age, sex, race, eye rubbing, mitral valve prolapse, handedness, collagen
      vascular disease, ocular trauma, pigmentary retinopathy, Marfan's syndrome,
      Down's syndrome, and a history of contact lens wear. METHODS: A case-control
      study was designed (n=120) with incident cases assembled from the years 1985-99.
      Controls were chosen from the same person-time experience as cases and were
      picked from a source population with multiple outcomes ensuring that none was
      knowingly related to any of the potential exposures being studied. Atopy was
      defined based on the UK working group 1994 definition (at least 4/6 criteria =
      complete, 3/6 criteria = incomplete, and at least 1/6 criteria = partial).
      Keratoconus was defined based on clinical criteria and previously published I-S
      values. Multiple logistic regression was used in the analysis to obtain the odds
      ratios as the measure of association. RESULTS: In the univariate associations,
      there was an association between keratoconus and atopy as well as eye rubbing and
      family history of keratoconus. However, in the multivariate analysis, only eye
      rubbing was still a significant predictor of keratoconus (odds ratio = 6.31 p =
      0.001). CONCLUSIONS: This study supports the hypothesis that the most significant
      cause of keratoconus is eye rubbing. Atopy may contribute to keratoconus but most
      probably via eye rubbing associated with the itch of atopy. No other variable
      measured was significantly associated with the aetiology of keratoconus.

PMID- 10906087
TI  - Effect of disagreement between refractive, keratometric, and topographic
      determination of astigmatic axis on suture removal after penetrating
      keratoplasty.
AB  - BACKGROUND/AIMS: Post-keratoplasty astigmatism can be managed by selective suture
      removal in the steep axis. Corneal topography, keratometry, and refraction are
      used to determine the steep axis for suture removal. However, often there is a
      disagreement between the topographically determined steep axis and sutures to be
      removed and that determined by keratometry and refraction. The purpose of this
      study was to evaluate any difference in the effect of suture removal, on visual
      acuity and astigmatism, in patients where such a disagreement existed. METHODS:
      37 cases (from 37 patients) of selective suture removal after penetrating
      keratoplasty, were included. In the first group "the disagreement group" (n=15)
      there was disagreement between corneal topography, keratometry, and refraction
      regarding the axis of astigmatism and sutures to be removed. In the second group
      "the agreement group" (n=22) there was agreement between corneal topography,
      keratometry, and refraction in the determination of the astigmatic axis and
      sutures to be removed. Sutures were removed according to the corneal topography,
      at least 5 months postoperatively. Vector analysis for change in astigmatism and
      visual acuity after suture removal was compared between groups. RESULTS: In the
      disagreement group, the amount of vector corrected change in refractive,
      keratometric, and topographic astigmatism after suture removal was 3.45 (SD
      2.34), 3.57 (1.63), and 2.83 (1. 68) dioptres, respectively. In the agreement
      group, the amount of vector corrected change in refractive, keratometric, and
      topographic astigmatism was 5.95 (3.52), 5.37 (3.29), and 4.71 (2.69) dioptres
      respectively. This difference in the vector corrected change in astigmatism
      between groups was statistically significant, p values of 0.02, 0.03, and 0.03
      respectively. Visual acuity changes were more favourable in the agreement group.
      Improvement or no change in visual acuity occurred in 90.9% in the agreement
      group compared with 73.3% of the disagreement group. CONCLUSIONS: Agreement
      between refraction, keratometry, and topography was associated with greater
      change in vector corrected astigmatism and was an indicator of good prognosis.
      Disagreement between refraction, keratometry, and topography was associated with
      less vector corrected change in astigmatism, a greater probability of decrease in
      visual acuity, and a relatively poor outcome following suture removal. However,
      patients in the disagreement group still have a greater chance of improvement
      than worsening, following suture removal.

PMID- 10906088
TI  - Corneal topography by keratometry.
AB  - AIMS: To investigate the ability of a telecentric keratometer to describe the
      asphericity and curvature of convex ellipsoidal surfaces and human corneas.
      METHODS: 22 conicoidal convex surfaces and 30 human corneas were examined by
      conventional keratometry. Additional keratometric measurements were made when the
      surface was tilted in the horizontal plane relative to the instrument optical
      axis. This resulted in a series of radius measurements derived from different
      regions of the surface. These measurements were used to determine the apical
      radius and the p value of the horizontal meridian of each surface. The results
      were compared with those derived from measurements using the EyeSys
      videokeratoscope and form Talysurf analysis. The method was repeated on 30 human
      corneas and the results compared with those of a videokeratoscope. RESULTS: For
      the aspheric buttons, the keratometric and the EyeSys results tended to give
      higher values for both apical radius and the p values than those of the Talysurf
      analysis. The best agreement was between the Talysurf and the keratometer where
      the results were not significantly different. For the human corneas, the apical
      radii were significantly different comparing the keratometer with the
      videokeratoscope but the p values were not significantly different. CONCLUSION:
      The keratometric method for assessing curvature and asphericity appears to hold
      promise as a method for quantifying the corneal topography.

PMID- 10906089
TI  - Audit of outcome of an extracapsular cataract extraction and posterior chamber
      intraocular lens training course.
AB  - BACKGROUND: A training course for cataract surgery with intraocular lens
      implantation was organised in April 1997 at the National Eye Centre, Kaduna,
      Nigeria. Operations were performed by six Nigerian consultant ophthalmologists
      under the supervision of two surgeons from Aravind Eye Hospital, India. METHODS:
      A total of 175 eyes with uncomplicated cataracts were operated on after careful
      selection. All but six patients had extracapsular cataract extraction with
      posterior chamber intraocular lens insertion during the training programme.
      RESULTS: The mean age of the patients at operation was 54. 2 years. One hundred
      and forty five of the operated eyes (85.8%) were blind before surgery of which
      six (3.6%) remained blind postoperatively. An uncorrected visual acuity of 6/60
      or better was achieved in 87.3% eyes after surgery. Forty one patients (24.3%)
      were blind before surgery, two of whom (1.2%) remained blind afterwards. The most
      common intraoperative complication was posterior capsular rent which occurred in
      10 eyes (5.7%); striate keratopathy/corneal oedema and cortical remnant were the
      most common immediate postoperative complications, occurring in 44.6% and 8.0%,
      respectively. CONCLUSION: With adequate surgical skills, extracapsular cataract
      extraction with posterior chamber intraocular lens implantation offers good
      visual rehabilitation even under training conditions.

PMID- 10906090
TI  - Ability of a confocal scanning laser ophthalmoscope (TopSS) to detect early
      glaucomatous visual field defect.
AB  - AIMS: To evaluate the ability of the confocal scanning laser ophthalmoscope
      (TopSS) to detect early glaucomatous visual field defect using our unique
      discriminant criteria. METHODS: The optic discs of 110 eyes of normal Korean
      subjects were examined and normal values for each variable were obtained
      according to the size of the optic disc. The five most sensitive optic disc
      variables for discriminating glaucoma were then applied to one eye of 80 Korean
      subjects with primary open angle glaucoma or normal tension glaucoma. Only eyes
      with an optic disc size of 2.0-3.0 mm(2) and a contour tilt of less than 3
      degrees were included. These variables were used to develop unique discriminant
      criteria for detecting early glaucomatous visual field defect and their
      sensitivity and specificity were calculated in three groups of patients with
      visual field loss. RESULTS: The five most sensitive variables were half the depth
      area, cup/disc (C/D) ratio, total area of the neuroretinal rim (NRR), volume
      above, and localised thinning of the NRR. The following criteria were used to
      diagnose glaucoma: (1) total area of the NRR decreased and one of the other four
      variables abnormal, and (2) total area of the NRR normal, localised thinning of
      the NRR, and one of the other three variables abnormal. The sensitivity of these
      criteria was 89.7% in patients with a mildly impaired visual field and 100% in
      those with a moderately or severely impaired visual field; the specificity was
      89.1%. CONCLUSIONS: The discriminant criteria used had high sensitivity and
      specificity in the diagnosis of glaucoma and the TopSS can be useful in the early
      detection of changes in the glaucomatous optic disc.

PMID- 10906091
TI  - Incidence of ocular side effects of topical beta blockers in the Netherlands.
AB  - BACKGROUND: Several ocular side effects including uveitis, have been reported
      following topical beta blocker treatment for glaucoma and ocular hypertension.
      The incidence of these side effects was investigated in the Netherlands. METHODS:
      A prospective observational design was used whereby monthly questionnaires were
      sent to all practising ophthalmologists in the Netherlands during 3 consecutive
      months. Questionnaires were returned at the end of each month. Any patient whose
      topical beta blocker therapy was altered because of an ocular reaction was noted
      on this questionnaire. Ophthalmologists who did not return their questionnaires
      were interviewed by telephone at the end of the study period. The number of
      patients using topical beta blockers was derived from drug sales figures.
      RESULTS: 70% (328/467) of the ophthalmologists in the Netherlands participated in
      the study. During the 3 month study period 34 cases were reported: 15 patients
      had periorbital dermatitis, in eight patients eyelids and conjunctiva were
      affected, in seven patients the conjunctiva was affected, and four patients had
      punctate keratitis. The calculated incidence of ocular side effects during
      topical beta blocker therapy was 1.51 cases/1000 patient years. CONCLUSION:
      Topical beta blocker therapy is associated with few clinically important ocular
      side effects. No cases of uveitis were reported.

PMID- 10906092
TI  - Long term results of glaucoma surgery among participants in an east African
      population survey.
AB  - AIM: To evaluate the long term results of glaucoma surgery among people in East
      Africa. METHODS: Participants in a population based survey of eye disease
      prevalence were offered glaucoma surgery using standardised criteria. Either
      surgical iridectomy or trabeculectomy was carried out as indicated by a medical
      officer or by one of two ophthalmologists. Trabeculectomy methods included
      releasable sutures and mitomycin C in the majority of eyes. Subjects were
      examined during the first week and 2 months after surgery. Nearly 3 years later,
      re-examination was carried out in those who were still resident in the region.
      RESULTS: Among 46 people who were offered iridectomy, trabeculectomy, or combined
      cataract extraction/lens implant/trabeculectomy, 21 people underwent surgery
      (46%). Of the 21, 19 were re-examined at 3 years (90%), including 16/18 eyes
      after trabeculectomy. Among these, intraocular pressure (IOP) declined from 29.9
      (SD 9.4) mm Hg to 14.7 (5.9) mm Hg, with 16 of 18 eyes (89%) achieving a
      reduction > 25%. Hypotony maculopathy, late bleb leak, and late endophthalmitis
      were not detected. Visually significant cataract developed in 5/15 re-examined
      eyes that underwent trabeculectomy alone (33%), possibly associated with pre
      existing cataract and diagnosis of angle closure glaucoma, but not with mitomycin
      C use. CONCLUSIONS: Nearly half of those with glaucoma among residents of rural
      African villages accepted the offer of surgical therapy. While technical success
      was achieved at satisfactory levels, the development of cataract must be
      considered an important issue for application of glaucoma surgical therapy
      programmes.

PMID- 10906093
TI  - Diabetic retinopathy in Victoria, Australia: the Visual Impairment Project.
AB  - AIM: To establish the prevalence, severity, and risk factors for diabetic
      retinopathy in a representative sample of Victorian residents aged 40 years and
      older. METHODS: A population based, cluster sampling method was used to recruit
      4744 participants (86% participation rate). Nine randomly selected, suburban
      Melbourne clusters and four randomly selected, rural Victorian clusters were
      used. Participants provided a detailed medical and personal history and underwent
      an ocular examination including funduscopy and fundus photography. Rural
      participants provided a blood sample, from which the glycosylated haemoglobin
      percentage was measured. The diagnosis of diabetic retinopathy was based on
      fundus photographs from participants with self reported diabetes. RESULTS: The
      prevalence of diabetic retinopathy among people with self reported diabetes was
      29. 1%. The prevalence of untreated, vision threatening retinopathy was 2.8%.
      Retinopathy was positively associated with a longer reported duration of diabetes
      diagnosis (p<0.01) and with higher fractions of glycosylated haemoglobin
      (p<0.01). Retinopathy was not significantly associated with age, ethnicity, body
      mass index, glaucoma, myopia or intake of alcohol, tobacco, or aspirin (all p >
      0.05). CONCLUSIONS: Most people in Victoria with proliferative diabetic
      retinopathy or clinically significant macular oedema have received laser
      treatment. There remains however, a small but important group who have not
      received treatment and whose vision is threatened. People with diabetes should be
      encouraged to maintain strict glycaemic control and to undergo regular screening
      to delay or prevent the development of retinopathy.

PMID- 10906094
TI  - Maculopathy in patients with diabetes mellitus type 1 and type 2: associations
      with risk factors.
AB  - AIM: To examine possible relation between diabetic maculopathy and various risk
      factors for diabetic complications in patients with diabetes mellitus type 1 and
      type 2. METHODS: Cross sectional study of two cohorts of diabetic patients,
      comprising 1796 patients with type 1 diabetes (mean age 47 years, mean duration
      of diabetes 24 years) and 1563 patients with type 2 diabetes (mean age 62 years,
      mean duration of diabetes 16 years). Retinopathy levels (R0-RV) and maculopathy
      were assessed by fluorescence angiography and fundus photography and binocular
      biomicroscopy. Diabetic neuropathy was assessed by means of computer assisted
      electrocardiography and by thermal and vibratory sensory examination. Patients
      were classified as normoalbuminuric (<20 microg/min) or microalbuminuric (20-200
      microg/min) according to their albumin excretion rates measured in urine
      collected overnight. Using univariate analyses, the effects of selected patient
      characteristics on the presence of maculopathy were evaluated. Multiple logistic
      regression analyses were performed to determine independent effects of risk
      variables on diabetic maculopathy. RESULTS: Background retinopathy (RII) was
      found to be present in 28% of type 1 diabetic patients and in 38% of type 2
      diabetic patients. The prevalence of maculopathy in these patients was remarkably
      high (42% in type 1 and 53% in type 2 diabetic patients). Patients with
      maculopathy had significantly impaired visual acuity. Multiple logistic
      correlation analysis revealed that in both types of diabetes maculopathy
      exhibited independent associations with duration of diabetes and with neuropathy
      (p <0. 01); in type 1 diabetic patients there were significant associations with
      age at diabetes onset, serum triglyceride and total cholesterol levels (p <0.05);
      in type 2 diabetes with serum creatinine levels and with hypertension (p <0.05).
      CONCLUSIONS: Irrespective of the type of diabetes, diabetic patients with long
      standing diabetes have a high risk for the development of diabetic maculopathy.
      Diabetic maculopathy is closely associated with diabetic nephropathy and
      neuropathy and with several atherosclerotic risk factors which suggests that
      these factors might have an important role in the pathogenesis of maculopathy.
      However, prospective trials are necessary to evaluate the predictive value of
      such factors. The findings of the present cross sectional study reinforce the
      arguments of previous studies by others for tight control of hypertension and
      hyperglycaemia.

PMID- 10906095
TI  - Screening for CMV retinitis using chromatic discrimination thresholds and
      achromatic contrast sensitivity.
AB  - BACKGROUND: Many patients with cytomegalovirus retinitis (CMVR) are unaware of
      visual disturbance so screening is advocated for patients with HIV and low CD4
      counts. Many tests of retinal function have been recommended but few are
      effective at detecting CMVR. We assess the potential of chromatic discrimination
      thresholds and achromatic contrast sensitivity as screening tests for patients
      with CMVR. METHOD: 11 HIV+ patients with CMVR, 16 age matched HIV+ patients, and
      29 age matched controls were recruited. Visual acuity, chromatic discrimination
      thresholds, and achromatic contrast sensitivity were measured. Fundal examination
      was performed by slit lamp biomicroscopy for HIV+ patients. Those with CMVR were
      photographed and the CMVR graded from the photographs. RESULTS: Loss of chromatic
      discrimination was found in patients with CMVR (tritan p<0.0005, red/green
      p<0.05). The same group had deterioration in achromatic contrast sensitivity at
      2.2, 3.4, and 10 cpd (p<0.05). There was correlation between the zone of CMVR
      with chromatic gratings (tritan r=0.83, p<0.005). No statistically significant
      difference was found between the HIV+ patients and the controls for all tests
      (p>0.1). CONCLUSIONS: HIV+ patients with CMVR have a loss of chromatic
      discrimination and achromatic contrast sensitivity and this may be used to screen
      HIV+ patients for CMVR.

PMID- 10906096
TI  - Effect of alcohol and light on the retinal pigment epithelium of normal subjects
      and patients with retinal dystrophies.
AB  - BACKGROUND: Light absorbed by photoreceptors causes oscillations in the voltage
      across the retinal pigment epithelium (RPE). This is the basis of the clinical
      test, electro-oculography (EOG). We have previously shown that alcohol causes a
      sequence of voltage changes which are so precisely the same as those caused by
      light that they must be produced by the same RPE machinery. There is good
      evidence that alcohol produces its effect by a direct action on the RPE.
      Consequently, in diseases associated with loss of photoreceptors, alcohol should
      continue to produce the voltage changes of the EOG unless secondary changes have
      occurred in the RPE. METHODS: The alcohol response in patients with retinitis
      pigmentosa (RP) was investigated using EOG. RESULTS: In no patient with RP was
      there any alcohol rise. CONCLUSION: In patients with RP secondary abnormalities
      of function of the RPE must occur.

PMID- 10906097
TI  - Anatomy of optic nerve radiations as assessed by static perimetry and MRI after
      tailored temporal lobectomy.
AB  - AIMS: To determine the course of optic nerve radiations in the temporal lobe,
      especially their retinotopic organisation and the anterior limit of the Meyer's
      loop. METHODS: 18 adult patients who had undergone a tailored temporal lobectomy
      for epilepsy were included in this study between 1994 and 1998. The rostrocaudal
      extent of the lateral temporal lobe resection assessed intraoperatively by the
      surgeon and by postoperative MRI was compared with the postoperative visual
      fields determined by automated static perimetry (ASP). RESULTS: 15 patients (83%)
      presented a postoperative visual field deficit (VFD) confined to the superior
      homonymous field contralateral to the side of the resection. All degrees from a
      minimal upper field loss to a complete quadrantanopia were observed. The VFDs
      were somewhat stereotyped, predominating along the vertical meridian. The
      smallest anteroposterior resection resulting in a VFD was limited to 20 mm from
      the tip of the temporal lobe. A relation was observed between the extent of the
      lateral resection in front of the second and third convolutions and the
      occurrence and extent of postoperative VFDs. No patient reported persisting
      subjective visual impairment. CONCLUSION: The high frequency of postoperative
      VFDs appears to be due to the greater sensitivity of ASP. The characteristics of
      the stereotyped VFDs allow new conclusions about the course and retinotopy of
      optic nerve radiations. The anterior limit of Meyer's loop is likely to be
      located more rostrally than previously believed.

PMID- 10906099
TI  - Pharmacological mydriasis and optic disc examination.
AB  - AIM: To determine whether pharmacological mydriasis leads to a significant
      difference in interobserver agreement of optic disc measurement compared with
      examination without mydriasis. METHOD: A cross sectional study was performed with
      a pair of observers examining the optic disc of two randomised groups of
      patients, one group before diagnostic mydriasis, and the other afterwards.
      Horizontal and vertical disc diameters and cup/disc ratios were measured with a
      78 dioptre lens. The study was repeated with another observer pair and two
      further groups of patients. RESULTS: In study A 86 subjects were examined in
      total (52 without and 34 with mydriasis). In study B 87 subjects were examined
      (45 without and 42 with mydriasis). The 95% limits of agreement of the cup/disc
      ratio measurement differences were significantly larger without mydriasis
      (p<0.001 for all studies (F test)). For both studies examination after mydriasis
      gave significantly greater agreement for vertical and horizontal cup/disc ratios.
      The cases with good agreement (0.1 difference or better) for vertical cup/disc
      ratios were 37/52 (72%) and 34 /45 (76%) without mydriasis and 33/34 (97%) and
      40/42 (95%) respectively with mydriasis. Similar differences were recorded for
      horizontal cup/disc ratios. Disc diameter measurement results showed similar
      differences in study A but were not affected by mydriasis in study B.
      CONCLUSIONS: Examination of the optic disc without pharmacological mydriasis
      gives significantly poorer interobserver agreement. In this study, the mean 95%
      limits of agreement values for all cup/disc ratio values were 0.27 for
      examination without mydriasis and 0.13 for examination with mydriasis. A measure
      outside these limits would suggest a real difference. This study indicates that
      mydriasis is important for reproducible clinical examination in glaucoma.

PMID- 10906098
TI  - Use of paper selectively absorbing long wavelengths to reduce the impact of
      educational near work on human refractive development.
AB  - BACKGROUND/AIMS: Educational near work has been identified as a major risk factor
      for the development of juvenile progressive myopia. A study was undertaken to
      determine whether differences in focal length resulting from longitudinal
      chromatic aberration of the eye can be exploited to reduce the impact of near
      work on refractive development. METHODS: Infrared photorefraction was used to
      determine refractive states in young adult volunteers performing a task similar
      to reading and writing under various spectral environments. The potential
      benefits of the observed differences in accommodation demand were studied with a
      computational model of emmetropisation and myopia progression. RESULTS: The
      refractive state was largely independent of the colour temperature of the
      illumination light (white paper) and the colour of commercially available papers
      (white illumination). Selective elimination of long wavelengths, however,
      significantly reduced the accommodation stimulus by about 0.5 dioptres.
      CONCLUSION: Results from model calculations suggest that the use of paper which
      selectively absorbs long wavelengths may significantly reduce the myopiagenic
      effects of educational near work.

PMID- 10906100
TI  - Expression of VLA-2, VLA-3, and alpha(v) integrin receptors in uveal melanoma:
      association with microvascular architecture of the tumour and prognostic value.
AB  - BACKGROUND: The interaction of the integrin receptors with their ligands
      (collagen, laminin, fibronectin, and others) has a crucial role during the
      reorganisation of the extracellular matrix and the metastatic process. The
      presence of particular vascular patterns in uveal melanoma is associated with the
      development of metastases. There is some evidence that interactions between the
      tumour cells and the extracellular matrix are responsible for the shape of these
      patterns. METHODS: The expression of VLA-2, VLA-3, and alpha(v) integrin
      receptors was examined by immunohistochemistry on paraffin embedded tumour
      specimens from 92 uveal melanomas (iris melanomas excluded). Possible
      correlations between these results and the tumour vascular patterns, the
      histological features of the tumours as well as the clinical outcome of the
      patients, were investigated. RESULTS: The expression of VLA-2 in tumours was
      associated with the presence of vascular networks (p = 0.05). Tumours with less
      than 25% VLA-3 positive cells infiltrated the sclera more frequently than those
      with more than 25% VLA-3 cell positivity (p = 0.05). Tumours expressing less than
      50% alpha(v) positive cells were associated with the mixed or epithelioid cell
      type (p = 0.05) and, with less statistical precision, with the presence of
      extraocular growth (p = 0.07). The univariate logistic regression analysis showed
      that the risk of developing metastases within the first 5 years after diagnosis
      did not depend on the expression of the integrin receptors investigated.
      CONCLUSION: The potential biological importance of the associations between
      integrin expression and the histopathological features of the tumours found in
      the present study remains to be elucidated in future experiments. The
      immunohistochemical detection of VLA-2, VLA-3, and alpha(v) integrins had no
      prognostic value in our preliminary report.

PMID- 10906101
TI  - Results of intraoperative mitomycin C application in dacryocystorhinostomy.
AB  - AIMS: To evaluate the long term results of intraoperative mitomycin C application
      in dacryocystorhinostomy (DCR) surgery compared with results of the conventional
      procedure. METHODS: In this prospective randomised controlled study, a total of
      88 eyes diagnosed with acquired nasolacrimal duct obstruction were randomly
      divided into a conventional DCR group and a mitomycin C group in which mitomycin
      C was used during DCR surgery. The surgical procedures in both groups were
      exactly the same, except that in the patients in the mitomycin C group, a piece
      of neurosurgical cottonoid soaked with 0.2 mg/ml mitomycin C was applied to the
      osteotomy site for 30 minutes. The results of the DCR surgeries were evaluated by
      objective findings such as irrigation and the height of tear meniscus and
      subjective symptoms by asking patients the condition of tearing improvement.
      RESULTS: Among the 44 eyes in the mitomycin C group, 95.5% of patients remained
      totally symptom free after 10 months of follow up; while in the conventional
      group, 70.5% of patients were reported to be symptom free and 18% of patients to
      have an improvement in their symptoms. There was a significant difference between
      these two groups. As far as objective findings were concerned, there were 41 eyes
      in the mitomycin C group classified as having a normal and one eye with moderate
      tear meniscus level, compared with 32 eyes and seven eyes, respectively, in the
      conventional group. There was also a significant difference between these two
      groups. The non-patency rate in the mitomycin C group is 4.5% compared with 11.4%
      in the conventional group. There were no complications such as abnormal nasal
      bleeding, mucosal necrosis, or infection except one patient with delayed wound
      healing. CONCLUSIONS: Intraoperative mitomycin C application is effective in
      increasing the success rate of DCR surgery in standard nasolacrimal duct
      obstruction, and no significant complications resulted from its use.

PMID- 10906102
TI  - Histological features of ocular adnexal lymphoma (REAL classification) and their
      association with patient morbidity and survival.
AB  - BACKGROUND: The histological characteristics of ocular adnexal lymphomas have
      previously provided only a limited guide to clinical outcome for affected
      patients. This clinicopathological relation was re-examined using the Revised
      European American Lymphoma (REAL) system to classify the tumours in a large
      cohort of patients. METHODS: The biopsies and clinical follow up data for 192
      patients with ocular adnexal lymphoma were reviewed, the biopsies being regraded
      in accordance with the REAL classification. For each of five histological groups,
      logistic regression analysis was used to determine the odds ratios (OR) for the
      presence of systemic disease at the time of orbital diagnosis and Cox regression
      analysis was used to assess the hazard ratios (HR) for disseminated disease and
      lymphoma related death. For 108 patients in whom extraorbital spread occurred,
      the histological category of lymphoma was compared with the sites of
      dissemination. RESULTS: At presentation, the frequency of previous or concurrent
      extraorbital disease increased from marginal zone lymphoma (OR 1.0), diffuse
      lymphoplasmacytic/lymphoplasmacytoid lymphoma (OR 2.3), follicle centre lymphoma
      (OR 3.8), diffuse large B cell lymphoma (OR 4.0) to other histological lymphoma
      variants (OR 26.8). For all histological types, the estimated risk of
      extraorbital disease and lymphoma related death continued for many years and the
      proportion of patients with at least one extraorbital recurrence after 5 years
      was 47% for MZL, 48% for LPL, 64% for FCL, 81% for DLCL, and 95% for other
      lymphoma variants. The corresponding estimated rates for 5 year lymphoma related
      mortality were 12%, 19%, 22%, 48%, and 53% respectively. CONCLUSIONS: Patients
      with ocular adnexal lymphoma can be classified by REAL into five distinct groups,
      which show a progressive increase in the risks of extraorbital disease at
      diagnosis, of disease dissemination with time, and of tumour related death.

PMID- 10906103
TI  - Local intra-arterial fibrinolysis for acute occlusion of the central retinal
      artery: a meta-analysis of the published data.
AB  - BACKGROUND/AIM: Central retinal artery occlusion (CRAO) is typically associated
      with a poor visual outcome. Several favourable reports of local intra-arterial
      fibrinolysis (LIF), which involves the superselective administration of a
      thrombolytic agent directly into the ophthalmic artery, have appeared in the
      recent literature. The aim of this study was to critically appraise these studies
      in a collective fashion. METHODS: A meta-analysis was performed of all the
      published literature germane to LIF in cases of CRAO. RESULTS: Of the 16 studies
      identified, all were retrospective and non-randomised. After correction for data
      duplication, the results of LIF in 100 patients can be reported. A final acuity
      of 6/6 or better was seen in 14% of patients following LIF, and a visual result
      of 6/12 or better was seen in 27% of subjects. A poor final acuity of 3/60 or
      worse was seen in 60.6% of eyes treated with local intra-arterial fibrinolysis.
      These results compare favourably with conventional forms of therapy. Potentially
      serious complications were seen in four patients, but no patient suffered a
      permanent neurological deficit. CONCLUSION: The results of this study suggest
      that there may be a marginal visual benefit associated with LIF compared with
      conventional management of CRAO. However, the methodology of the cited studies
      was often unsatisfactory, and a randomised controlled trial of LIF in cases of
      CRAO is justified. Outside of a randomised clinical trial, the use of
      superselective fibrinolytic therapy for CRAO cannot be recommended on the basis
      of current evidence.

PMID- 10906104
TI  - Otolaryngological findings in congenital nasolacrimal duct obstruction and
      implications for prognosis.
AB  - AIM: To investigate otolaryngological abnormalities associated with congenital
      nasolacrimal duct obstruction (CNLDO) and their effect on the prognosis. METHODS:
      65 consecutive cases of CNLDO were followed up with routine
      otorhinolaryngological examination with tympanometry. RESULTS: Otitis media with
      effusion (OME) and uvula bifida were detected in 44.6% and 9.2% of the children,
      respectively. Medical treatment and probing were less effective in patients with
      OME (p<0. 05). CONCLUSIONS: OME and uvula bifida are significant anomalies
      associated with CNLDO and the former has a marked effect on the prognosis. This
      finding may help to determine the patients who will need further treatment after
      massage and probing.

PMID- 10906105
TI  - Helping blind and partially sighted people to read: the effectiveness of low
      vision aids.
AB  - AIMS: To substantiate the claim that low vision aids reduce the degree of
      disability associated with visual impairment. METHODS: An observational study of
      vision, ocular pathology, age, sex, and reading ability in new referrals to a low
      vision clinic. Reading ability was assessed both with the patients' own
      spectacles and with an appropriate low vision aid. RESULTS: The reading
      performance and biographical characteristics of new referrals to a low vision
      clinic were recorded. Data were collected for 168 people over a 6 month period.
      Upon arrival at the clinic the mean functional visual acuity equated to 6/36 and
      77% of patients were unable to read newsprint (N8). After a low vision assessment
      and provision of a suitable low vision aid 88% of new patients were able to read
      N8 or smaller text. CONCLUSIONS: The degree of visual impairment observed in new
      referrals to a low vision clinic is sufficient to prevent the majority from
      performing many daily tasks. Low vision aids are an effective means of providing
      visual rehabilitation, helping almost nine out of 10 patients with impaired
      vision to read.

PMID- 10906107
TI  - Advancing microsurgical instrumentation into the 21st century.

PMID- 10906108
TI  - Central serous chorioretinopathy complicated by massive bilateral subretinal
      haemorrhage.

PMID- 10906106
TI  - Molecular ophthalmology: an update on animal models for retinal degenerations and
      dystrophies.

PMID- 10906109
TI  - Retinopathy and myopia of prematurity.

PMID- 10906110
TI  - Cell subpopulations in failed human corneal grafts.

PMID- 10906111
TI  - Late onset lattice dystrophy.

PMID- 10906113
TI  - The art of LASIK

PMID- 10906112
TI  - Topical analgesia during retinal laser photocoagulation.

PMID- 10906114
TI  - Clinical ocular photography

PMID- 10906115
TI  - Ophthalmic ultrasound: a diagnostic atlas

PMID- 10906117
TI  - Developments in ophthalmology. Vol 32 mycosis of the eye and its adnexa

PMID- 10906116
TI  - Clear corneal lens surgery

PMID- 10906118
TI  - Topics in international health: trachoma

PMID- 10906119
TI  - Regulation of Lef-mediated transcription and p53-dependent pathway by associating
      beta-catenin with CBP/p300.
AB  - CBP and its homologue p300 play significant roles in cell differentiation, cell
      cycle, and anti-oncogenesis. We demonstrated that beta-catenin, recently known as
      a potent oncogene, and CBP/p300 are associated through its CH3 region, which is a
      primary target of adenoviral oncoprotein E1A and various nuclear proteins, such
      as p53, cyclin E, and AP-1, and both are colocalized in the nuclear bodies.
      CBP/p300 potentiated Lef-mediated transactivation of beta-catenin, and E1A, a
      potent inhibitor of CBP/p300, repressed its transactivation. Furthermore,
      overexpression of stable beta-catenin mutant competitively suppressed the p53
      dependent pathway. These may be a key mechanism of beta-catenin involved in
      oncogenic events underlying disruption of tumor suppressor function through
      CBP/p300.

PMID- 10906120
TI  - Thermus aquaticus DNA polymerase I mutants with altered fidelity. Interacting
      mutations in the O-helix.
AB  - Phe(667) in the conserved O-helix of Thermus aquaticus (Taq) DNA polymerase I
      (pol I) is known to be important for discrimination against dideoxy-NTPs. We show
      here that Phe(667) is also important for base selection fidelity. In a forward
      mutation assay at high polymerase concentration, wild type pol I catalyzed
      frequent A --> T and G --> T transversions and -1 frameshifts at nonreiterated
      sites involving loss of a purine immediately downstream of a pyrimidine. The
      mutants F667L and A661E,I665T,F667L exhibited large decreases in A --> T and G -
      > T transversions, and the triple mutant displayed reduction in the
      aforementioned -1 frameshifts as well. Kinetic analysis showed that the F667L and
      A661E,I665T,F667L polymerases discriminated against synthesis of A:A mispairs
      more effectively and catalyzed less extension of A:A mispairs than the wild type
      enzyme. These data indicate that Phe(667) functions in maintaining the error
      frequency and spectrum, and the catalytic efficiency, of wild type pol I. We also
      found that the strong general mutator activity conferred by the single A661E
      substitution was entirely suppressed in the A661E, I665T,F667L polymerase,
      exemplifying how interactions among O-helix residues can contribute to fidelity.
      We discuss the mutator and anti-mutator mutations in light of recently obtained
      three-dimensional structures of T. aquaticus pol I.

PMID- 10906121
TI  - Interaction of chromogranin B and the near N-terminal region of chromogranin B
      with an intraluminal loop peptide of the inositol 1,4, 5-trisphosphate receptor.
AB  - Given the interaction of the inositol 1,4,5-trisphosphate receptor (IP(3)R) with
      chromogranins A (CGA) and B (CGB), two major Ca(2+) storage proteins of secretory
      granules that have been shown to be IP(3)-sensitive intracellular Ca(2+) store of
      neuroendocrine cells, we have investigated the potential interaction of the
      intraluminal loop regions of the IP(3)R with both intact CGB and the conserved
      near N-terminal region of CGB. The interaction studies carried out with CGB and
      glutathione S-transferase fusion proteins of intraluminal loop regions of bovine
      type 1 IP(3)R showed that CGB interacts with intraluminal loop 3-2 (the second
      loop formed between transmembrane regions 5 and 6) of the IP(3)R at both pH 5.5
      and 7.5. Analytical ultracentrifugation studies also indicated that CGB interacts
      with the same intraluminal loop region of the IP(3)R and the interaction was much
      stronger than that between CGA and the loop. Moreover, the conserved near N
      terminal region of CGB also interacted with the intraluminal loop region of the
      IP(3)R. The CGB interaction with the IP(3)R intraluminal loop peptide at pH 7.5
      showed a DeltaG(0) value of -8.1 kcal/mol at 37 degrees C for a 1:1
      stoichiometry, indicating a K(d) of approximately 1.9 micrometer. These results
      give insight into the molecular organization of the IP(3)-sensitive Ca(2+) store.

PMID- 10906122
TI  - Physical and functional interaction between two pluripotent proteins, the Y-box
      DNA/RNA-binding factor, YB-1, and the multivalent zinc finger factor, CTCF.
AB  - CTCF is a unique, highly conserved, and ubiquitously expressed 11 zinc finger
      (ZF) transcriptional factor with multiple DNA site specificities. It is able to
      bind to varying target sequences to perform different regulatory roles, including
      promoter activation or repression, creating hormone-responsive gene silencing
      elements, and functional block of enhancer-promoter interactions. Because
      different sets of ZFs are utilized to recognize different CTCF target DNA sites,
      each of the diverse DNA.CTCF complexes might engage different essential protein
      partners to define distinct functional readouts. To identify such proteins, we
      developed an affinity chromatography method based on matrix-immobilized purified
      recombinant CTCF. This approach resulted in isolation of several CTCF protein
      partners. One of these was identified as the multifunctional Y-box DNA/RNA
      binding factor, YB-1, known to be involved in transcription, replication, and RNA
      processing. We examined CTCF/YB-1 interaction by reciprocal immunoprecipitation
      experiments with anti-CTCF and anti-YB-1 antibodies, and found that CTCF and YB-1
      form complexes in vivo. We show that the bacterially expressed ZF domain of CTCF
      is fully sufficient to retain YB-1 in vitro. To assess possible functional
      significance of CTCF/YB-1 binding, we employed the very first identified by us,
      negatively regulated, target for CTCF (c-myc oncogene promoter) as a model in co
      transfection assays with both CTCF and YB-1 expression vectors. Although
      expression of YB-1 alone had no effect, co-expression with CTCF resulted in a
      marked enhancement of CTCF-driven c-myc transcriptional repression. Thus our
      findings demonstrate, for the first time, the biological relevance of the CTCF/YB
      1 interaction.

PMID- 10906123
TI  - Identification of motifs for cell adhesion within the repeated domains of
      transforming growth factor-beta-induced gene, betaig-h3.
AB  - betaig-h3 is a transforming growth factor-beta-inducible cell adhesion molecule
      that has four characteristic homologous repeated domains. We made recombinant
      betaig-h3 proteins, which were highly active in mediating human corneal
      epithelial (HCE) cell adhesion and spreading. The 2nd and the 4th repeated
      domains were sufficient to mediate HCE cell adhesion. A sequence analysis showed
      that aspartic acid (Asp) and isoleucine (Ile) of the 2nd and the 4th domains are
      highly conserved in many fasciclin 1 homologous (fas-1) domains. Substitution
      mutational study identified these two amino acids are essential for cell
      adhesion. Synthetic peptides containing Asp and Ile, NKDIL and EPDIM derived from
      the 2nd and the 4th domains, respectively, almost completely blocked cell
      adhesion mediated by not only wild type betaig-h3 but also each of the 2nd and
      the 4th domains. These peptides alone were fully active in mediating cell
      adhesion. In addition, we demonstrated the functional receptor for betaig-h3 is
      alpha(3)beta(1) integrin. These results, therefore, establish the essential
      motifs within the 2nd and the 4th domains of betaig-h3, which interact with
      alpha(3)beta(1) integrin to mediate HCE cell adhesion to betaig-h3 and suggest
      that other proteins containing Asp-Ile in their fas-1 domains could possibly
      function as cell adhesion molecules.

PMID- 10906124
TI  - Mutations in the N-terminal cooperativity domain of gene 32 protein alter
      properties of the T4 DNA replication and recombination systems.
AB  - The gene 32 protein (gp32) of bacteriophage T4 is the essential single-stranded
      DNA (ssDNA)-binding protein required for phage DNA replication and recombination.
      gp32 binds ssDNA with high affinity and cooperativity, forming contiguous
      clusters that optimally configure the ssDNA for recognition by DNA polymerase or
      recombination enzymes. The precise roles of gp32 affinity and cooperativity in
      promoting replication and recombination have yet to be defined, however. Previous
      work established that the N-terminal "B-domain" of gp32 is essential for
      cooperativity and that point mutations at Arg(4) and Lys(3) positions have
      varying and dramatic effects on gp32-ssDNA interactions. Therefore, we examined
      the effects of six different gp32 B-domain mutants on T4 in vitro systems for DNA
      synthesis and homologous pairing. We find that the B-domain is essential for
      gp32's stimulation of these reactions. The stimulatory efficacy of gp32 B-domain
      mutants generally correlates with the hierarchy of relative ssDNA binding
      affinities, i.e. wild-type gp32 approximately R4K > K3A approximately R4Q > R4T >
      R4G gp32-B. However, the functional defect of a particular mutant is often
      greater than can be explained simply by its ability to saturate the ssDNA at
      equilibrium, suggesting additional defects in the proper assembly and activity of
      DNA polymerase and recombinase complexes on ssDNA, which may derive from a
      decreased lifetime of gp32-ssDNA clusters.

PMID- 10906125
TI  - Domain-specific interaction with the I kappa B kinase (IKK)regulatory subunit IKK
      gamma is an essential step in tax-mediated activation of IKK.
AB  - The human T-cell leukemia virus type 1 Tax oncoprotein deregulates the NF-kappa B
      signaling pathway by persistently stimulating a key signal transducer, the I
      kappa B kinase (IKK). Tax physically associates with the IKK regulatory subunit,
      IKK gamma, although the underlying biochemical mechanism and functional
      significance remain unclear. We show that the Tax-IKK gamma interaction requires
      two homologous leucine zipper domains located within IKK gamma. These leucine
      zipper domains are unique for the presence of a conserved upstream region that is
      essential for Tax binding. Site-directed mutagenesis analysis revealed that a
      leucine-repeat region of Tax is important for IKK gamma binding. Interestingly,
      all the Tax mutants defective in IKK gamma binding failed to engage the IKK
      complex or stimulate IKK activity, and these functional defects can be rescued by
      fusing the Tax mutants to IKK gamma. These results provide mechanistic insights
      into how Tax specifically targets and functionally activates the cellular kinase
      IKK.

PMID- 10906126
TI  - Isolation and characterization of two novel phosphodiesterase PDE11A variants
      showing unique structure and tissue-specific expression.
AB  - cDNAs encoding a novel phosphodiesterase, phosphodiesterase 11A (PDE11A), were
      isolated by a combination of reverse transcriptase-polymerase chain reaction
      using degenerate oligonucleotide primers and rapid amplification of cDNA ends.
      Their catalytic domain was identical to that of PDE11A1 (490 amino acids)
      reported during the course of this study. However, the cDNAs we isolated had N
      termini distinct from PDE11A1, indicating two novel N-terminal variants of
      PDE11A. PDE11A3 cDNA encoded a 684-amino acid protein including one complete and
      one incomplete GAF domain in the N-terminal region. PDE11A4 was composed of 934
      amino acids including two complete GAF domains and shared 630 C-terminal amino
      acids with PDE11A3 but had a distinct N terminus containing the putative
      phosphorylation sites for cAMP- and cGMP-dependent protein kinases. PDE11A3
      transcripts were specifically expressed in testis, whereas PDE11A4 transcripts
      were particularly abundant in prostate. Recombinant PDE11A4 expressed in COS-7
      cells hydrolyzed cAMP and cGMP with K(m) values of 3.0 and 1.4 microm,
      respectively, and the V(max) value with cAMP was almost twice that with cGMP.
      Although PDE11A3 showed the same K(m) values as PDE11A4, the relative V(max)
      values of PDE11A3 were approximately one-sixth of those of PDE11A4. PDE11A4, but
      not PDE11A3, was phosphorylated by both cAMP- and cGMP-dependent protein kinases
      in vitro. Thus, the PDE11A gene undergoes tissue-specific alternative splicing
      that generates structurally and functionally distinct gene products.

PMID- 10906127
TI  - Distinct topologies of mono- and decavanadate binding and photo-oxidative
      cleavage in the sarcoplasmic reticulum ATPase.
AB  - UV irradiation of the sarcoplasmic reticulum (SR) ATPase in the presence of
      vanadate cleaves the enzyme at either of two different sites. Under conditions
      favoring the presence of monovanadate, and in the presence of Ca(2+), ADP, and
      Mg(2+), cleavage results in two fragments of 71- and 38-kDa electrophoretic
      mobility. On the other hand, under conditions permitting formation of
      decavanadate, and in the absence of Ca(2+) and ADP, cleavage results in two
      fragments of 88- and 21-kDa electrophoretic mobility. The amino terminus
      resulting from cleavage is blocked and resistant to Edman degradation. However,
      the initial photo-oxidation product can be reduced with NaB(3)H(4,) resulting in
      incorporation of radioactive (3)H label. Extensive digestion of the labeled
      protein with trypsin then yields labeled peptides that are specific for the each
      of the photo-oxidation conditions, and can be sequenced after purification.
      Collection of the Edman reaction fractional products reveals the radioactive
      label and demonstrates that Thr(353) is the residue oxidized by monovanadate at
      the phosphorylation site (i.e. Asp(351)). Correct positioning of monovanadate at
      the phosphorylation site requires binding of Mg(2+) and ADP to the Ca(2+)
      dependent conformation of the enzyme. Subsequent hydrolytic cleavage is likely
      assisted by the neighboring Asp(601), and yields the 71- and 38-kDa fragments. On
      the other hand, Ser(186) (and possibly the following three residues: Val(187),
      Ile(188), and Lys(189)) is the residue that is photo-oxidized by decavanadate in
      the absence of ADP. Hydrolytic cleavage of the oxidized product at this site is
      likely assisted by neighboring acidic residues, and yields the 88- and 21-kDa
      fragments. The bound decavanadate, which we find to produce steric interference
      with TNP-AMP binding, must therefore extend to the A domain (i.e. small cytosolic
      loop) in order to oxidize Ser(186). This protein conformation is only obtained in
      the absence of Ca(2+).

PMID- 10906128
TI  - Two types of functionally distinct NAD(P)H dehydrogenases in Synechocystis sp.
      strain PCC6803.
AB  - The ndhD gene encodes a membrane protein component of NAD(P)H dehydrogenase. The
      genome of Synechocystis sp. PCC6803 contains 6 ndhD genes. Three mutants were
      constructed by disrupting highly homologous ndhD genes in pairs. Only the
      DeltandhD1/DeltandhD2 (DeltandhD1/D2) mutant was unable to grow under
      photoheterotrophic conditions and exhibited low respiration rate, although the
      mutant grew normally under photoautotrophic conditions in air. The
      DeltandhD3/DeltandhD4 (DeltandhD3/D4) mutant grew very slowly in air and did not
      take up CO(2). The results demonstrated the presence of two types of functionally
      distinct NAD(P)H dehydrogenases in Synechocystis PCC6803 cells.
      TheDeltandhD5/DeltandhD6 (DeltandhD5/D6) mutant grew like the wild-type strain.
      Under far-red light (>710 nm), the level of P700(+) was high in DeltandhD1/D2 and
      M55 (ndhB-less mutant) at low intensities. The capacity of Q(A) (tightly bound
      plastoquinone) reduction by plastoquinone pool, as measured by the fluorescence
      increase in darkness upon addition of KCN, was much less in DeltandhD1/D2 and M55
      than in DeltandhD3/D4 and DeltandhD5/D6. We conclude that electrons from NADPH
      are transferred to the plastoquinone pool mainly by the NdhD1.NdhD2 type of
      NAD(P)H dehydrogenases.

PMID- 10906130
TI  - Inter- and intrasubunit interactions during the formation of RNA polymerase
      assembly intermediate.
AB  - We used yeast two-hybrid and in vitro co-immobilization assays to study the
      interaction between the Escherichia coli RNA polymerase (RNAP) alpha and beta
      subunits during the formation of alpha(2)beta, a physiological RNAP assembly
      intermediate. We show that a 430-amino acid-long fragment containing beta
      conserved segments F, G, H, and a short part of segment I forms a minimal domain
      capable of specific interaction with alpha. The alpha-interacting domain is held
      together by protein-protein interactions between beta segments F and I. Residues
      in catalytically important beta segments H and I directly participate in alpha
      binding; substitutions of strictly conserved segment H Asp(1084) and segment I
      Gly(1215) abolish alpha(2)beta formation in vitro and are lethal in vivo. The
      importance of these beta amino acids in alpha binding is fully supported by the
      structural model of the Thermus aquaticus RNAP core enzyme. We also demonstrate
      that determinants of RNAP assembly are conserved, and that a homologue of beta
      Asp(1084) in A135, the beta-like subunit of yeast RNAP I, is responsible for
      interaction with AC40, the largest alpha-like subunit. However, the A135-AC40
      interaction is weak compared with the E. coli alpha-beta interaction, and A135
      mutation that abolishes the interaction is phenotypically silent. The results
      suggest that in eukaryotes additional RNAP subunits orchestrate the enzyme
      assembly by stabilizing weak, but specific interactions of core subunits.

PMID- 10906129
TI  - Expression of an active Na,K-ATPase with an alpha-subunit lacking all twenty
      three native cysteine residues.
AB  - We have constructed a mutant Na,K-ATPase alpha1-subunit with all native cysteine
      residues replaced. Using the baculovirus system, this cysteine-less alpha1
      subunit and wild-type beta1-subunit were expressed in High Five cells. After 3
      days of infection, cells were fractionated, and endoplasmic reticulum, Golgi
      apparatus, and plasma membranes were isolated. The molecular activity of the
      cysteine-less mutant in the plasma membranes was close to the wild-type protein
      (8223 min(-)(1) versus 6655 min(-)(1)). Cation and ATP activation of Na,K-ATPase
      activities revealed that replacing all 23 cysteines resulted in only a 50%
      reduction of K(m) for Na(+), a 2-fold increase in K(m) for K(+), and no changes
      in K(m) for ATP. The distribution of alpha-subunits among the membranes showed a
      high percentage of cysteine-less protein in the endoplasmic reticulum and Golgi
      apparatus compared with the wild-type protein. Furthermore, the cellular
      stability of the alphabeta assembly appeared reduced in the cysteine-less mutant.
      Cells harvested after more than 3 days of infection showed extensive degradation
      of the cysteine-less alpha-subunit, which is not observed with the wild-type
      enzyme. Thus the Na,K-ATPase contains no cysteine residues that are critical for
      function, but the folding and/or assembly pathway of this enzyme is affected by
      total cysteine substitution.

PMID- 10906131
TI  - Complex formation of adenomatous polyposis coli gene product and axin facilitates
      glycogen synthase kinase-3 beta-dependent phosphorylation of beta-catenin and
      down-regulates beta-catenin.
AB  - Adenomatous polyposis coli gene product (APC) functions as a tumor suppressor and
      its mutations in familial adenomatous polyposis and colorectal cancers lead to
      the accumulation of cytoplasmic beta-catenin. The molecular mechanism by which
      APC regulates the stability of beta-catenin was investigated. The central region
      of APC, APC-(1211-2075), has the beta-catenin- and Axin-binding sites and down
      regulates beta-catenin. Glycogen synthase kinase-3 beta (GSK-3 beta)
      phosphorylated beta-catenin slightly in the presence of either APC-(1211-2075) or
      Axin(delta)(beta)(-catenin), in which the beta-catenin-binding site is deleted,
      and greatly in the presence of both proteins. The enhancement of the GSK-3 beta
      dependent phosphorylation of beta-catenin was eliminated by the APC-binding site
      of Axin. Axin down-regulated beta-catenin in SW480 cells, but not
      Axin(delta)(beta)(-catenin). In L cells where APC is intact, Axin(delta)(beta)(
      catenin) inhibited Wnt-dependent accumulation of beta-catenin but not Axin-(298
      832)(delta)(beta)(-catenin) in which the APC- and beta-catenin-binding sites are
      deleted. These results indicate that the complex formation of APC and Axin
      enhances the phosphorylation of beta-catenin by GSK-3 beta, leading to the down
      regulation of beta-catenin.

PMID- 10906132
TI  - A novel action of human apurinic/apyrimidinic endonuclease: excision of L
      configuration deoxyribonucleoside analogs from the 3' termini of DNA.
AB  - beta-l-Dioxolane-cytidine (l-OddC, BCH-4556, Troxacitabine) is a novel unnatural
      stereochemical nucleoside analog that is under phase II clinical study for cancer
      treatment. This nucleoside analog could be phosphorylated and subsequently
      incorporated into the 3' terminus of DNA. The cytotoxicity of l-OddC was
      correlated with the amount of l-OddCMP in DNA, which depends on the incorporation
      by DNA polymerases and the removal by exonucleases. Here we reported the
      purification and identification of the major enzyme that could preferentially
      remove l-OddCMP compared with dCMP from the 3' termini of DNA in human cells.
      Surprisingly, this enzyme was found to be apurinic/apyrimidinic endonuclease
      (APE1) (), a well characterized DNA base excision repair protein. APE1 preferred
      to remove l- over d-configuration nucleosides from 3' termini of DNA. The
      efficiency of removal of these deoxycytidine analogs were as follows: l-OddC >
      beta-l-2',3'-dideoxy-2', 3'-didehydro-5-fluorocytidine > beta-l-2',3'
      dideoxycytidine > beta-l-2',3'-dideoxy-3'-thiocytidine > beta-d-2',3'
      dideoxycytidine > beta-d-2',2'-difluorodeoxycytidine > beta-d-2'-deoxycytidine
      >/= beta-d-arabinofuranosylcytosine. This report is the first demonstration that
      an exonuclease can preferentially excise l-configuration nucleoside analogs. This
      discovery suggests that APE1 could be critical for the activity of l-OddC or
      other l-nucleoside analogs and may play additional important roles in cells that
      were not previously known.

PMID- 10906133
TI  - A novel cellular protein (MTBP) binds to MDM2 and induces a G1 arrest that is
      suppressed by MDM2.
AB  - The MDM2 protein, through its interaction with p53, plays an important role in
      the regulation of the G(1) checkpoint of the cell cycle. In addition to binding
      to and inhibiting the transcriptional activation function of the p53 protein,
      MDM2 binds, inter alia, to RB and the E2F-1.DP-1 complex and in so doing may
      promote progression of cells into S phase. Mice transgenic for Mdm2 possess cells
      that have cell cycle regulation defects and develop an altered tumor profile
      independent of their p53 status. MDM2 also blocks the growth inhibitory effects
      of transforming growth factor-beta1 in a p53-independent manner. We show here
      that a novel growth regulatory molecule is also the target of MDM2-mediated
      inhibition. Using a yeast two-hybrid screen, we have identified a gene that
      encodes a novel cellular protein (MTBP) that binds to MDM2. MTBP can induce G(1)
      arrest, which in turn can be blocked by MDM2. Our results suggest the existence
      of another growth control pathway that may be regulated, at least in part, by
      MDM2.

PMID- 10906134
TI  - Regulation of DNA-dependent protein kinase activity by ionizing radiation
      activated abl kinase is an ATM-dependent process.
AB  - Ionizing radiation (IR) treatment results in activation of the nonreceptor
      tyrosine kinase c-Abl because of phosphorylation by ATM. In vitro evidence
      indicates that DNA-dependent protein kinase (DNA-PK) can also phosphorylate and
      thus potentially activate Abl kinase activity in response to IR exposure. To
      unravel the role of ATM and DNA-PK in the activation of Abl, we assayed Abl, ATM,
      and DNA-PK activity in ATM- and DNA-PKcs-deficient cells after irradiation. Our
      results show that despite the presence of higher than normal levels of DNA-PK
      kinase activity, c-Abl fails to become activated after IR exposure in ATM
      deficient cells. Conversely, normal activation of both ATM and c-Abl occurs in
      DNA-PKcs-deficient cells, indicating that ATM but not DNA-PK is required for
      activation of Abl in response to IR treatment. Moreover, activation of Abl kinase
      activity by IR correlates well with activation of ATM activity in all phases of
      the cell cycle. These results indicate that ATM is primarily responsible for
      activation of Abl in response to IR exposure in a cell cycle-independent fashion.
      Examination of DNA-PK activity in response to IR treatment in Abl-deficient cells
      expressing mutant forms of Abl or in normal cells exposed to an inhibitor of Abl
      suggests an in vivo role for Abl in the down-regulation of DNA-PK activity.
      Collectively, these results suggest a convergence of the ATM and DNA-PK pathways
      in the cellular response to IR through c-Abl kinase.

PMID- 10906135
TI  - Gelonin is an unusual DNA glycosylase that removes adenine from single-stranded
      DNA, normal base pairs and mismatches.
AB  - We reported that plant ribosome inactivating proteins (RIP) have a unique DNA
      glycosylase activity that removes adenine from single-stranded DNA (Nicolas, E.,
      Beggs, J. M., Haltiwanger, B. M., and Taraschi, T. F. (1998) J. Biol. Chem. 273,
      17216-17220). In this investigation, we further characterized the interaction of
      the RIP gelonin with single-stranded oligonucleotides and investigated its
      activity on double-stranded oligonucleotides. At physiological pH, zinc and beta
      mercaptoethanol stimulated the adenine DNA glycosylase activity of gelonin. Under
      these conditions, gelonin catalytically removed adenine from single-stranded DNA
      and, albeit to a lesser extent, from normal base pairs and mismatches in duplex
      DNA. Also unprecedented was the finding that activity on single-stranded and
      double-stranded oligonucleotides containing multiple adenines generated unstable
      products with several abasic sites, producing strand breakage and duplex melting,
      respectively. The results from competition experiments suggested similar
      interactions between gelonin's DNA-binding domain and oligonucleotides with and
      without adenine. A re-examination of the classification of gelonin as a DNA
      glycosylase/AP lyase using the borohydride trapping assay revealed that gelonin
      was similar to the DNA glycosylase MutY: both enzymes are monofunctional
      glycosylases, which are trappable to their DNA substrates. The k(cat) for the
      removal of adenine from single-stranded DNA was close to the values observed with
      multisubstrate DNA glycosylases, suggesting that the activity of RIPs on DNA may
      be physiologically relevant.

PMID- 10906137
TI  - The alpha subunits of Gz and Gi interact with the eyes absent transcription
      cofactor Eya2, preventing its interaction with the six class of homeodomain
      containing proteins.
AB  - Yeast two-hybrid techniques were used to identify possible effectors for the
      heterotrimeric G protein G(z) in human bone marrow cells. Eya2, a human homologue
      of the Drosophila Eya transcription co-activator, was identified. Eya2 interacts
      with activated Galpha(z) and at least one other member of the Galpha(i) family,
      Galpha(i2). Interactions were confirmed in mammalian two-hybrid and glutathione S
      transferase fusion protein pull-down assays. Regions of Eya2-mediating
      interaction were mapped to the C-terminal Eya consensus domain. Eya2 is an
      intrinsically cytosolic protein that is translocated to the nucleus by members of
      the Six homeodomain-containing family of proteins. Activated Galpha(z) and
      Galpha(i2) prevent Eya2 translocation and inhibit Six/Eya2-mediated activation of
      a reporter gene controlled through the MEF3/TATA promoter. Although G proteins
      are known to regulate the activity of numerous transcription factors, this
      regulation is normally achieved indirectly via one or more intermediates. We show
      here a novel functional regulation of a co-activator directly by G protein
      subunits.

PMID- 10906136
TI  - The structural basis of DNA target discrimination by papillomavirus E2 proteins.
AB  - The papillomavirus E2 proteins regulate the transcription of all papillomavirus
      genes and are necessary for viral DNA replication. Disruption of the E2 gene is
      commonly associated with malignancy in cervical carcinoma, indicating that E2 has
      a role in regulating tumor progression. Although the E2 proteins from all
      characterized papillomaviruses bind specifically to the same 12-base pair DNA
      sequence, the cancer-associated human papillomavirus E2 proteins display a unique
      ability to detect DNA flexibility and intrinsic curvature. To understand the
      structural basis for this phenomenon, we have determined the crystal structures
      of the human papillomavirus-18 E2 DNA-binding domain and its complexes with high
      and low affinity binding sites. The E2 protein is a dimeric beta-barrel and the
      E2-DNA interaction is accompanied by a large deformation of the DNA as it
      conforms to the E2 surface. DNA conformation and E2-DNA contacts are similar in
      both high and low affinity complexes. The differences in affinity correlate with
      the flexibility of the DNA sequence. Preferences of E2 proteins from different
      papillomavirus strains for flexible or prevent DNA targets correlate with the
      distribution of positive charge on their DNA interaction surfaces, suggesting a
      role for electrostatic forces in the recognition of DNA deformability.

PMID- 10906138
TI  - Regulation of the meiosis-inhibited protein kinase, a p38(MAPK) isoform, during
      meiosis and following fertilization of seastar oocytes.
AB  - A p38(MAPK) homolog Mipk (meiosis-inhibited protein kinase) was cloned from
      seastar oocytes. This 40-kDa protein shares approximately 65% amino acid identity
      with mammalian p38-alpha isoforms. Mipk was one of the major tyrosine
      phosphorylated proteins in immature oocytes arrested at the G(2)/M transition of
      meiosis I. The tyrosine phosphorylation of Mipk was increased in response to
      anisomycin, heat, and osmotic shock of oocytes. During 1-methyladenine-induced
      oocyte maturation, Mipk underwent tyrosine dephosphorylation and remained
      dephosphorylated in mature oocytes and during the early mitotic cell divisions
      until approximately 12 h after fertilization. At the time of differentiation and
      acquisition of G phases in the developing embryos, Mipk was rephosphorylated on
      tyrosine. In oocytes that were microinjected with Mipk antisense oligonucleotides
      and subsequently were allowed to mature and become fertilized, differentiation
      was blocked. Because MipK antisense oligonucleotides and a dominant-negative
      (K62R)Mipk when microinjected into immature oocytes failed to induce germinal
      vesicle breakdown, inhibition of Mipk function was not sufficient by itself to
      cause oocyte maturation. These findings point to a putative role for Mipk in cell
      cycle control as a G-phase-promoting factor.

PMID- 10906139
TI  - Syk is required for the activation of Akt survival pathway in B cells exposed to
      oxidative stress.
AB  - Syk has been demonstrated to play a crucial role in oxidative stress signaling in
      B cells. Here we report that Syk is required for the activation of the
      phosphatidylinositol (PI) 3-kinase-Akt survival pathway in B cells exposed to
      oxidative stress. Phosphorylation and activation of the serine-threonine kinase
      Akt were markedly increased in B cells treated with H(2)O(2). In Syk-deficient
      DT40 cells treated with low doses of H(2)O(2) (10-100 microm), Akt activation was
      considerably reduced. Pretreatment with wortmannin, a PI 3-kinase-specific
      inhibitor, completely blocked the Syk-dependent Akt activation. Following
      stimulation by low doses of H(2)O(2), a significant increase in PI 3-kinase
      activity was found in wild-type but not in Syk-deficient cells. These findings
      suggest that PI 3-kinase mediates Syk-dependent Akt activation pathway.
      Furthermore, viability of Syk-deficient cells, after exposure to H(2)O(2), was
      dramatically decreased and caspase-9 activity was greatly increased compared with
      that of the wild-type cells. These results suggest that Syk is essential for the
      Akt survival pathway in B cells and enhances cellular resistance to oxidative
      stress-induced apoptosis.

PMID- 10906140
TI  - On the Ca2+ dependence of non-transferrin-bound iron uptake in PC12 cells.
AB  - Non-transferrin-bound iron (NTBI) uptake has been reported to follow two
      pathways, Ca(2+)-dependent and Ca(2+)-independent (Wright, T. L., Brissot, P.,
      Ma, W. L., and Weisiger, R. A. (1986) J. Biol. Chem. 261, 10909-10914; Sturrock,
      A., Alexander, J., Lamb, J., Craven, C. M., and Kaplan, J. (1990) J. Biol. Chem.
      265, 3139-3145). Studies reporting the two pathways have ignored the weak
      interactions of Ca(2+) with the chelator nitrilotriacetate (NTA) and the reducing
      agent ascorbate. These studies used a constant ratio of total Fe(2+) to NTA with
      and without Ca(2+). We observed Ca(2+) activation of NTBI uptake in PC12 cells
      with the characteristics reported for other cells upon using 1 mm ascorbate and a
      constant ratio of total Fe(2+) to NTA with or without Ca(2+). However, Ca(2+) did
      not affect NTBI uptake in solutions without NTA. We then determined conditional
      stability constants for NTA binding to Ca(2+) and Fe(2+) by potentiometry under
      conditions of NTBI uptake experiments (pH, ionic strength, temperature,
      ascorbate, total Fe(2+), and total Ca(2+) concentrations). In solutions based on
      these constants and taking Ca(2+) chelation into account, Ca(2+) did not affect
      NTBI uptake over a range of free Fe(2+) concentrations. Thus, the Ca(2+)
      activation of NTBI uptake observed using the constant total Fe(2+) to NTA ratio
      was because of Ca(2+)-NTA chelation rather than an activation of the NTBI
      transporter itself. It is suggested that the previously reported Ca(2+)
      dependence of NTBI uptake be re-evaluated.

PMID- 10906141
TI  - Novel topological features of FhaC, the outer membrane transporter involved in
      the secretion of the Bordetella pertussis filamentous hemagglutinin.
AB  - Many pathogenic Gram-negative bacteria secrete virulence factors across the cell
      envelope into the extracellular milieu. The secretion of filamentous
      hemagglutinin (FHA) by Bordetella pertussis depends on the pore-forming outer
      membrane protein FhaC, which belongs to a growing family of protein transporters.
      Protein alignment and secondary structure predictions indicated that FhaC is
      likely to be a beta-barrel protein with an odd number of transmembrane beta
      strands connected by large surface loops and short periplasmic turns. The
      membrane topology of FhaC was investigated by random insertion of the c-Myc
      epitope and the tobacco etch virus protease-specific cleavage sequence. FhaC was
      fairly permissive to short linker insertions. Furthermore, FhaC appeared to
      undergo conformational changes upon FHA secretion. Surface detection of the
      inserted sequences indicated that several predicted loops in the C-terminal
      moiety as well as the N terminus of the protein are exposed. However, a large
      surface-predicted region in the N-terminal moiety of FhaC was inaccessible from
      the surface. In addition, the activity and the stability of the protein were
      affected by insertions in that region, indicating that it may have important
      structural and/or functional roles. The surface exposure of the N terminus and
      the presence of an odd number of beta-strands are novel features for beta-barrel
      outer membrane proteins.

PMID- 10906143
TI  - Synaptotagmin regulation of coated pit assembly.
AB  - Synaptotagmins bind clathrin AP-2 with high affinity via their second C(2)
      domain, which indicates they are involved in coated pit function. We now report
      that expression of synaptotagmins lacking either the second C(2) domain or the
      entire cytoplasmic region potently inhibit endocytosis. Inhibition was dependent
      on two intramembrane cysteine residues that were found to be essential for
      synaptotagmin oligomerization. Cells expressing the wild-type, but not the
      mutant, truncated synaptotagmin fragment had a reduced number of clathrin-coated
      pits. These results suggest that the formation of synaptotagmin multimers is an
      important step in the regulation of coated pit assembly.

PMID- 10906142
TI  - Grb3-3 is up-regulated in HIV-1-infected T-cells and can potentiate cell
      activation through NFATc.
AB  - The MAPK pathway is required for T-cell activation; however, its role in
      modulating T-cell function following human immunodeficiency virus type 1 (HIV-1)
      infection is poorly understood. In this report, we investigated whether Grb3-3,
      an isoform of the Grb2 (growth factor receptor-bound protein-2) adaptor molecule
      that is associated with the MAPK pathway, could be involved. We found that Grb3
      3, but not its isoform Grb2, is markedly up-regulated in CD4(+) peripheral blood
      mononuclear cells derived from either in vitro HIV-1-infected cultures or HIV-1
      infected human subjects. Analysis of HIV-1 gene products indicated that Tat and
      Nef, both of which have been implicated in modulating T-cell function, can
      independently induce expression of Grb3-3. By using NFAT/AP-1, AP-1, or NFAT
      reporter assays, we found that Grb3-3 can potentiate NFAT (but not AP-1) promoter
      activity in Jurkat T-cells upon engagement of the T-cell receptor and CD28 co
      receptor. In addition, potentiation of NFAT by Grb3-3 is substantially suppressed
      by MEKK1, a kinase that may play an important role in retaining NFAT in the
      cytoplasm, and by cyclosporin A. Finally, we also found that Grb3-3 potentiates
      HIV-1 long terminal (LTR) repeat promoter activity following T-cell receptor
      stimulation, an effect that can be largely suppressed by cyclosporin A. Taken
      together, this study indicates that Grb3-3 is a cellular factor that can be up
      regulated by HIV-1. In addition, Grb3-3 can also function as a positive factor
      for T-cell activation and, in doing so, may aid in establishing an intracellular
      environment that can optimally support HIV-1 replication.

PMID- 10906144
TI  - Analysis of the functional role of a G.A sheared base pair by in vitro genetics.
AB  - A classical genetic strategy has been combined with an in vitro selection method
      to search for functional interactions between the two domains of the hairpin
      ribozyme. G(21) is located within internal loop B; it is proposed to form a
      sheared base pair with A(43) across loop B and to bind a Mg(2+) ion. Both
      nucleotides are important for ribozyme function, and G.A sheared base pairs are a
      very widespread motif in structured RNA. We took advantage of its presence in the
      hairpin ribozyme to study its functional role. Pseudorevertants, in which the
      loss of G(21) was compensated by mutations at other positions, were isolated by
      in vitro selection. The vast majority of G(21) revertants contained substitutions
      within domain A, pointing to functional communication between specific sites
      within the two domains of the hairpin ribozyme. The possibility of a direct or
      redundant contacts is supported by electrophoretic mobility shift studies showing
      that a complex formed between domain B of the ribozyme and the substrate was
      disrupted and restored by base substitutions that have analogous effects on
      catalytic activity. The functional significance of this complex, the role of the
      nucleotides involved, and the basis for magnesium ion requirement is discussed.

PMID- 10906145
TI  - Roles of the Dal82p domains in allophanate/oxalurate-dependent gene expression in
      Saccharomyces cerevisiae.
AB  - Allophanate/oxalurate-induced gene expression in Saccharomyces cerevisiae
      requires at least five transcription factors, four of which act positively
      (Gln3p, Gat1p, Dal81p, and Dal82p) and one negatively (Dal80p). Gln3p binds to
      and Gat1p is proposed to bind to single GATA sequences; Dal80p binds to pairs of
      specifically oriented and spaced GATA sequences, and Dal82p binds to a pathway
      specific element, UIS(ALL). Dal82p consists of at least three domains as follows:
      (i) UIS(ALL) DNA-binding, (ii) transcriptional activation, and (iii) coiled
      coil(DAL82). Here we show that the coiled-coil(DAL82) domain possesses two
      demonstrable functions. (i) It prevents Dal82p-mediated transcription when
      inducer is absent. (ii) It is a major, although not exclusive, domain through
      which the inducer signal is received. Supporting the latter conclusion, a 38
      amino acid fragment, containing little more than the coiled-coil(DAL82) domain,
      supports oxalurate-inducible, Dal81p-dependent, reporter gene transcription.
      Dal81p is required for inducer responsiveness of LexAp-Dal82p and LexAp coiled
      coil(DAL82)-mediated transcription but isn't needed for inducer-dependent
      activation mediated by a Dal82p containing deletions in both the coiled
      coil(DAL82), UIS(ALL)-binding domains. There may be an interaction between Dal81p
      and the coiled-coil(DAL82) domain since (i) Dal81p is required for transcription
      mediated by LexA-coiled-coil(DAL82)p and (ii) a Dal81p-Dal82p complex is detected
      by two-hybrid assay.

PMID- 10906146
TI  - Cdk2-dependent phosphorylation and functional inactivation of the pRB-related
      p130 protein in pRB(-), p16INK4A(+) tumor cells.
AB  - The retinoblastoma family proteins pRB, p107, and p130 are phosphorylated and
      released from E2Fs in the late G(1) phase of the cell cycle. This phosphorylation
      is thought to contribute to the derepression of E2F-responsive genes and to be
      mediated, in part, by Cdk4 and Cdk6. Evidence that Cdk4/6 activity is inhibited
      by p16(INK4A) in most pRB(-) cells suggests that p107 and p130 may be
      underphosphorylated and remain associated with E2Fs during G(1)-S progression in
      cells that lack pRB. To examine this, we evaluated the cell cycle-dependent
      phosphorylation and E2F binding abilities of p107 and p130 in pRB(-), p16(+) Saos
      2 osteosarcoma cells. p130, but not p107, was phosphorylated and released from
      E2F-4 in late G(1) and S phase cells, although p130 phosphorylation differed
      qualitatively in these and other pRB(-), p16(+) cells as compared with pRB(+),
      p16(-) cell types. p130 phosphorylation occurred in the absence of cyclin D
      Cdk4/6 complexes, coincided with cyclin E- and Cdk2-associated kinase activity,
      and was prevented by expression of dominant negative Cdk2. Moreover, dominant
      negative Cdk2 prevented the dissociation of endogenous p130-E2F-4 complexes and
      inhibited E2F-4-dependent transcription. These findings show that p130 can be
      phosphorylated and functionally inactivated in a Cdk2-dependent process, and they
      highlight the involvement of distinct Cdks in the regulation of different pRB
      family proteins.

PMID- 10906147
TI  - The identification of a nonclassical cadherin expressed during B cell development
      and its interaction with surrogate light chain.
AB  - A 130-kDa glycoprotein (p130) has been found to be associated with surrogate
      light chain on pro- and pre-B I cells. Using peptide sequences obtained from
      purified p130 we have cloned its gene. The gene encodes a typical cadherin type 1
      membrane protein with six extracellular cadherin domains (one pseudo domain) but
      lacking the catenin-binding site in its cytoplasmic part. Even without this
      catenin-binding site, p130 mediates Ca(2+)-dependent homotypic adhesion of cells.
      The interaction of p130 with surrogate light chain is confirmed by co
      transfection and co-immunoprecipitation experiments. The expression of p130 is
      biphasic during the B cell development. Reverse transcriptase-polymerase chain
      reaction and flow cytometric analyses revealed that it is expressed on B220(+)c
      Kit(+) pro-B and pre-B-I cells as well as on B220(+)CD25(-)IgM(+) immature and
      mature B cells but not on B220(+)CD25(+) pre-B-II cells. It is also expressed in
      fetal liver, at low levels in myeloid cells, and strongly in intestinal
      epithelial cells. In the spleen, p130-expressing cells are mainly localized in
      the marginal zone. We call this B lineage-, intestine-, liver- and leukocyte
      expressed gene BILL-cadherin. The possible functions of BILL-cadherin in B cell
      development are discussed.

PMID- 10906148
TI  - Cyclization of polyubiquitin by the E2-25K ubiquitin conjugating enzyme.
AB  - For most substrates of ubiquitin (Ub)-dependent degradation, recognition by the
      proteasome is mediated by a covalently attached signal assembled from multiple
      ubiquitins linked to each other via the C terminus of one Ub and the epsilon
      amine of Lys(48) of another Ub. Among Ub-conjugating enzymes, E2-25K is unique in
      its ability to synthesize in vitro unanchored Lys(48)-linked poly-Ub chains from
      mono- or poly-Ub, E1, and ATP; thus, E2-25K has distinct binding sites for donor
      and acceptor (poly)Ub. During studies of chain assembly by E2-25K, we observed
      that Lys(48)-linked tri-Ub was efficiently converted to a new species that upon
      SDS-polyacrylamide gel electrophoresis migrated between linear di-Ub and tri-Ub.
      Analysis of this product by mass spectrometry and tryptic digestion showed that
      it was a cyclic form of tri-Ub. Cyclization of tri-Ub requires E1, E2-25K, ATP,
      and that the linear substrate has a free Gly(76) C terminus on the proximal end
      Ub and a Lys(48) side chain available on the distal end Ub. E2-25K similarly can
      catalyze the cyclization of longer poly-Ub chains, including tetra- and penta-Ub.
      Although cyclic tri-Ub resists hydrolysis by the PA700 or isopeptidase T
      deubiquitinating enzymes, it can be disassembled to Ub monomers by
      isopeptidase(s) in a red blood cell extract. Thus, if cyclic poly-Ub forms in
      vivo, it will not accumulate as a dead-end product.

PMID- 10906150
TI  - Endothelium-dependent relaxation of small resistance vessels is impaired in
      patients with autosomal dominant polycystic kidney disease.
AB  - Impaired endothelium-dependent relaxation has been demonstrated previously in
      resistance vessels of Han:SPRD polycystic kidney disease rats. The aim of the
      present study was to investigate whether endothelium-dependent relaxation is
      reduced also in patients with autosomal dominant polycystic kidney disease
      (ADPKD) and whether this is influenced by the nitric oxide (NO) system. Small
      subcutaneous resistance vessels from normotensive ADPKD patients with normal or
      near-normal renal function (n = 9) and from healthy control subjects (n = 10)
      were mounted in a Mulvany-Halpern myograph. The morphology of the vessels and
      acetylcholine (ACh)-induced endothelium-dependent relaxation, as well as 3
      morpholino-sydnonimine (SIN-1, NO donor)-induced endothelium-independent
      relaxation were investigated. The results showed that: (1) there were no
      significant differences in morphologic parameters of resistance vessels between
      the two groups; (2) the maximal ACh-induced relaxation rate was decreased in
      ADPKD patients compared with control subjects (71.5 +/- 12.1 versus 85.2 +/-
      8.7%, P < 0.01); (3) in the presence of L-arginine (a substrate of NO synthase),
      a left shift of the ACh dose-response curves was found in control subjects, but
      not in ADPKD patients; (4) in the presence of the N(G)-nitro-L-arginine methyl
      ester (an inhibitor of NO synthase), a right shift of the ACh dose-response curve
      was found in control subjects, but not in ADPKD patients; and (5) endothelium
      independent relaxation rate induced with SIN-1 was similar in patients and
      control subjects. In conclusion, endothelium-dependent relaxation was impaired in
      resistance vessels from patients with ADPKD. The reduced response of the vessels
      to both the substrate and inhibitor of NO synthase in ADPKD suggests that an
      impairment of NO synthase may be involved in the mechanism of endothelial
      dysfunction in ADPKD.

PMID- 10906151
TI  - Metabolism alters the selectivity of angiotensin-(1-7) receptor ligands for
      angiotensin receptors.
AB  - The present study examined whether metabolism of the putative angiotensin-(1-7)
      receptor agonist and antagonist [angiotensin-(1-7) and D-alanine(7) angiotensin
      (1-7), respectively] altered their ability to interact with angiotensin AT(1),
      AT(2), and AT(4) receptor subtypes. Both angiotensin-(1-7) and D-alanine(7)
      angiotensin-(1-7) competed with low affinity for (125)I-sarcosine(1),
      isoleucine(8) angiotensin II binding to AT(1) and AT(2) receptors in rat liver
      and adrenal medulla membranes, respectively, and competed with low affinity for
      (125)I-angiotensin IV binding to AT(4) receptors in bovine kidney epithelial cell
      membranes. In vitro renal metabolism of the angiotensin-(1-7) receptor ligands
      (incubating peptides with rat cortical tissue homogenates) had minimal influence
      on low-affinity binding to AT(1) and AT(2) receptors, yet caused a significant
      and dramatic shift toward high-affinity binding for AT(4) receptors. Low-affinity
      angiotensin II binding to the AT(4) receptor was also shifted toward high
      affinity binding following renal metabolism of the peptide. Conversely,
      angiotensins with high affinity for the AT(4) receptor (e.g., angiotensin IV)
      were shifted toward low-affinity binding states following peptide metabolism.
      Incubation of (125)I-angiotensin-(1-7) with rat cortical tissue generated the
      high-affinity AT(4) receptor ligand (125)I-angiotensin-(3-7), whereas the renal
      metabolism of (125)I-angiotensin II generated both (125)I-angiotensin-(3-7) and
      (125)I-angiotensin IV. These results reveal that renal metabolism of angiotensin
      (1-7) receptor ligands and angiotensin II yields products that have high affinity
      for the AT(4) receptor and could potentially contribute to the biologic actions
      of the parent peptide in the kidney.

PMID- 10906149
TI  - Cell-type specific targeting of the alpha 2c-adrenoceptor. Evidence for the
      organization of receptor microdomains during neuronal differentiation of PC12
      cells.
AB  - We have previously shown differences in the intracellular targeting of alpha2a
      (alpha(2A))- and alpha2c (alpha(2C))-adrenoreceptors expressed in the same cell
      line (von Zastrow, M., Link, R., Daunt, D. , Barsh, G., and Kobilka, B. (1993) J.
      Biol. Chem. 268, 763-766; Daunt, D. A., Hurt, C., Hein, L., Kallio, J., Feng, F.,
      and Kobilka, B. K. (1997) Mol. Pharmacol. 51, 711-720). alpha(2A)-Adrenoreceptors
      reside primarily in the plasma membrane in HEK 293 cells, while co-expressed
      alpha(2C)-adrenoreceptors are found mainly in an intracellular compartment. Since
      alpha(2c)-adrenoreceptors are expressed primarily in the brain, we compared the
      intracellular targeting of alpha(2C)-adrenoreceptors in two neuroendocrine cell
      lines with the targeting in three epithelial cell lines and one fibroblast cell
      line. In transiently transfected COS7 cells, and in stably transfected normal rat
      kidney cells, Madin-Darby canine kidney cells, and Rat1 fibroblasts, a
      significant proportion of alpha(2C)-adrenoreceptor detected by
      immunocytochemistry co-localized with markers for both the endoplasmic reticulum
      and the cis/medial Golgi compartments. In contrast, both PC12 cells and AtT20
      cells efficiently targeted alpha(2C)-adrenoreceptors to the plasma membrane.
      Ligand binding and Western blot analyses indicate that intracellular receptor in
      normal rat kidney cells is functional and undergoes normal post-translational
      processing. In PC12 cells the expressed alpha(2C)-adrenoreceptors become
      concentrated in neurite outgrowths in discrete regions of the plasma membrane
      having a high density of F-actin following treatment with nerve growth factor.
      These findings provide evidence for cell-type specific factors that facilitate
      the targeting of the G protein-coupled receptors to the plasma membrane.

PMID- 10906152
TI  - Reactive oxygen species stimulate p44/42 mitogen-activated protein kinase and
      induce p27(Kip1): role in angiotensin II-mediated hypertrophy of proximal tubular
      cells.
AB  - Angiotensin II (AngII) induces G(1) phase arrest and hypertrophy of cultured
      renal proximal tubular cells. In previous studies, it was shown that these
      effects depend on oxygen radical-mediated induction of p27(Kip1), an inhibitor of
      cyclin-dependent kinases. The present study was undertaken to investigate whether
      mitogen-activated protein (MAP) kinases serve as signaling intermediates between
      AngII-induced oxidative stress and induction of p27(Kip1). AngII (10(-7) M)
      induces a biphasic phosphorylation pattern of p44/42 MAP kinase with an early
      phosphorylation after 2 min and a later, second phosphorylation peak after
      prolong incubation (12 h) in cultured proximal tubular cells from two different
      species (MCT and LLC-PK(1) cells). Total protein expression of MAP kinase was not
      changed by AngII. These phosphorylation patterns of p44/42 MAP kinase caused
      activation of the enzyme, as detected by phosphorylated MAP substrate Elk-1 after
      immuno-precipitation of MAP kinase. Exogenous H(2)O(2) also stimulates a biphasic
      phosphorylation of p44/42 MAP kinase. The flavoprotein inhibitor diphenylene
      iodinium, as well as the antioxidant N-acetylcysteine, prevented AngII-induced
      p44/42 MAP kinase phosphorylation, indicating involvement of reactive oxygen
      species generated by membrane-bound NAD(P)H oxidase. The MAP kinase kinase
      inhibitor PD98059 completely inhibits AngII-induced p27(Kip1) expression and
      (3)[H]leucine incorporation into proteins as a previously established marker of
      cell hypertrophy. PD98059 did not attenuate AngII-stimulated intracellular
      synthesis of oxygen radicals. Transient transfection with p44/42 MAP kinase
      antisense, but not sense, phosphorothioate-modified oligonucleotides also
      prevented AngII-induced MAP kinase phosphorylation, p27(Kip1) expression, and
      cell hypertrophy. Furthermore, induction of p27(Kip1) by H(2)O(2) was also
      abolished in the presence of PD98059. Although AngII induces phosphorylation of
      the stress-activated p38 MAP kinase, inhibition of this enzyme with SB203580
      failed to attenuate induced p27(Kip1) expression and hypertrophy. These data
      provide evidence that AngII- mediated oxygen stress leads to the phosphorylation
      of p44/42 MAP kinase in proximal tubular cells. Activation of this enzyme is
      essential for p27(Kip1) expression, G(1) phase arrest, and hypertrophy of
      proximal tubular cells. These findings may lead to new concepts concerning
      interference of the development of proximal tubular hypertrophy, which may
      eventually turn into a maladaptive process in vivo leading ultimately to tubular
      atrophy and tubulointerstitial fibrosis.

PMID- 10906153
TI  - Requirement of cyclin D1 in mesangial cell mitogenesis.
AB  - Abstract. Hyperplasia of mesangial cells (MC) is a frequent finding in
      glomerulonephritis. The control and function of cyclin D1, a regulator of cell
      cycle progression, in MC proliferation in vivo and in vitro were investigated. In
      a rat model of mesangioproliferative glomerulonephritis, increases in the number
      of cyclin D1-positive MC nuclei were prominent on day 5 of the disease, preceding
      the peak of MC hyperplasia. In growth-arrested rat MC in culture, mitogenic
      stimulation with serum or platelet-derived growth factor (PDGF) led to rapid
      increases in cyclin D1 protein expression. Transforming growth factor-beta1
      inhibited PDGF induction of cyclin D1 protein at 12 h. In an examination of the
      subcellular distribution of cyclin D1, it was observed that stimulation of MC
      with PDGF for 6 h caused translocation of cyclin D1 from the cytoplasm into the
      nucleus. Coincubation with PDGF and transforming growth factor-beta1 completely
      inhibited this effect, without altering the cellular cyclin D1 protein abundance
      at that time point. To test whether reduction of cyclin D1 protein levels was
      sufficient to inhibit mitogenesis, MC were transfected with antisense
      oligonucleotides (ODN) complementary to rat cyclin D1 mRNA. Antisense ODN against
      cyclin D1 reduced the serum- or PDGF-induced protein expression of cyclin D1 to
      27 or 10% of control levels, respectively. These inhibitory effects were
      correlated with diminished cyclin-dependent kinase 4 activity. Antisense ODN
      against cyclin D1 also decreased the PDGF-induced increase in p21(Waf-1) protein
      levels. The MC proliferation caused by serum or PDGF was markedly inhibited by
      antisense ODN against cyclin D1, as measured by [(3)H]thymidine uptake and cell
      counts. It is concluded that increased cyclin D1 protein expression of MC is
      required for MC proliferation. Targeting cyclin D1 expression may represent an
      effective means to inhibit MC proliferation in vitro and in vivo.

PMID- 10906154
TI  - Gastrin releasing peptide-preferring bombesin receptors mediate growth of human
      renal cell carcinoma.
AB  - Bombesin-like peptides typically act as neurotransmitters along the brain-gut
      axis and as growth factors in various human tissues. The present study
      demonstrates the expression of gastrin releasing peptide (GRP)-preferring
      bombesin receptors in human renal cell carcinoma but not in normal kidney tissue.
      The expression of GRP receptors was characterized at the mRNA level by reverse
      transcription-PCR, as well as at the protein level by binding of (125)I-[Tyr(4)]
      bombesin to membranes prepared from tumor tissue (K(d) 0.3 nM) and healthy kidney
      tissue from the same four patients. GRP receptors were also demonstrated in four
      human kidney carcinoma cell lines (A-498, CAKI-1, CAKI-2, and ACHN). The effects
      of bombesin/GRP agonists and/or antagonists on growth were investigated in vitro
      on CAKI-2 cells, which expressed large amounts of GRP receptors. Cell numbers
      stimulated by 10% fetal calf serum were significantly stimulated by interleukin
      1beta (control) and GRP-7 (10(-7) M), both in the range of 136 to 148%; addition
      of the GRP receptor antagonist acetyl-GRP(20-27) (10(-6) M) completely reversed
      this effect. Bombesin alone (10(-6) M) significantly stimulated CAKI-2 cells
      (129%) cultured with 0.5% fetal calf serum, whereas another antagonist, D
      Phe6,Leu13,(CH2NH)Leu14 bombesin(6-14) (1 microM), alone did not inhibit growth,
      thus excluding an autocrine mechanism. These results indicate for the first time
      that malignant transformation of human kidney tissue into renal cell carcinoma is
      accompanied by novel expression of GRP receptors. Bombesin-like peptides might
      act as mitogens in these carcinomas, and they might be useful as diagnostic or
      therapeutic tools such as tumor imaging or internal radiotherapy.

PMID- 10906155
TI  - Growth hormone increases inducible nitric oxide synthase expression in mesangial
      cells.
AB  - Mice transgenic for bovine growth hormone (GH) develop progressive
      glomerulosclerosis. However, the proximal signaling events that lead to increased
      matrix deposition in this pathologic condition are still unclear. Components of
      the L-arginine metabolic pathway, especially inducible nitric oxide (NO) synthase
      (iNOS), ornithine aminotransferase (OAT), and ornithine decarboxylase (ODC), have
      been associated with glomerular scarring. In this study, mesangial cells were
      treated with GH, and the expression of iNOS, ODC, and OAT was determined using
      reverse transcription-PCR. In addition, nitrite accumulation in the conditioned
      media of mesangial cell cultures was measured in the presence or absence of GH.
      The findings revealed that GH increased iNOS transcript levels in a dose
      dependent manner, with the highest levels being attained at GH concentrations of
      20 to 50 ng/ml. The GH-induced increase in iNOS transcript levels was accompanied
      by a significant increase in nitrite concentrations in conditioned media, which
      was blocked by the addition of L-N(G)-monomethylarginine. The effect of GH (50
      ng/ml) in eliciting nitrite production was as potent as that of bacterial
      lipopolysaccharide (10 microg/ml). The expression of OAT and ODC, in contrast,
      was not altered at any of the GH concentrations tested. GH receptor mRNA was also
      expressed by mesangial cells, independently of the GH concentration present in
      the cell culture medium. These data indicate that GH may interact with its
      receptor to regulate the L-arginine/NO pathway in mesangial cells, by directly
      modulating iNOS expression and NO production, without altering the
      arginase/OAT/ODC pathway.

PMID- 10906156
TI  - Strong and selective glomerular localization of CD134 ligand and TNF receptor-1
      in proliferative lupus nephritis.
AB  - CD134 (OX40) is a member of the tumor necrosis factor (TNF) receptor (TNFR)
      family that can be expressed on activated T lymphocytes. Interaction between
      CD134 and its ligand (CD134L) is involved in costimulation of T and B lymphocyte
      activation, and in T cell adhesion to endothelium. To examine the possible role
      of this interaction in the pathogenesis of systemic lupus erythematosus (SLE),
      expression of CD134 and CD134L on peripheral blood leukocytes was studied, and no
      significant differences between SLE patients and control individuals were found.
      Immunohistology on renal biopsies from patients with lupus nephritis or other
      renal disorders, using a recombinant human CD134-containing chimeric molecule to
      detect CD134L, demonstrated the abundant presence of CD134L in all cases of
      proliferative lupus nephritis in a granular distribution predominantly along the
      epithelial side of the glomerular capillary wall. Confocal laser scanning
      microscopy indicated colocalization with subepithelial immune deposits. In none
      of the other renal disorders examined, including nonproliferative forms of lupus
      nephritis, was glomerular staining for CD134L detected in a similar pattern.
      Endothelial CD134L expression was frequently observed in different types of
      vasculitis. CD134 was detected on perivascular infiltrating leukocytes and on
      part of the tubular epithelium, but not on glomerular resident cells.
      Immunohistology for several other TNF(R) family members revealed in proliferative
      lupus nephritis a similar distribution for TNFR1 as was observed for CD134L. In
      contrast, glomerular expression of TNFR2 was similar in all cases examined. The
      glomerular presence of CD134L and TNFR1 in proliferative lupus nephritis in
      association with subepithelial immune deposits may be of pathogenetic
      significance and have diagnostic value.

PMID- 10906157
TI  - Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial
      nephropathy.
AB  - This study examines the clinical features, pathologic findings, and outcome of 24
      patients with biopsy-proven lithium toxicity. The patient population was 50%
      male, 87.5% Caucasian, and had a mean age of 42.5 yr (range, 26 to 57). Mean
      duration of lithium therapy for bipolar disorder was 13.6 yr (range, 2 to 25).
      All patients were biopsied for renal insufficiency (mean serum creatinine 2.8
      mg/dl; range, 1.3 to 8.0), with associated proteinuria >1.0 g/d in 41.7%.
      Nephrotic proteinuria (>3.0 g/d) was present in 25%. Other features included
      nephrogenic diabetes insipidus in 87% and hypertension in 33.3%. Renal biopsy
      revealed a chronic tubulointerstitial nephropathy in 100%, with associated
      cortical and medullary tubular cysts (62.5%) or dilatation (33.3%). All of the
      renal cysts stained for epithelial membrane antigen, while 51.4% stained with
      lectin Arachis hypogaea, and only 3.8% stained with Tetragonolobus purpureas,
      indicating they originated from distal and collecting tubules. The degree of
      tubular atrophy and interstitial fibrosis was graded as severe in 58.3%, moderate
      in 37.5%, and mild in 4.2% of cases. There was a surprisingly high prevalence of
      focal segmental glomerulosclerosis (50%) and global glomerulosclerosis (100%),
      sometimes of equivalent severity to the chronic tubulointerstitial disease. The
      significant degree of foot process effacement (mean 34%, five of 14 cases with
      >50%) suggests a potential direct glomerular toxicity. Focal segmental
      glomerulosclerosis correlated with proteinuria >1.0 g/d (P = 0.0014, Fisher exact
      test). Despite discontinuation of lithium, seven of nine patients with initial
      serum creatinine values >2.5 mg/dl progressed to end-stage renal disease (ESRD).
      Only three patients, all with initial serum creatinine <2.1 mg/dl, had subsequent
      improvement in renal function. By Kaplan-Meier survival analysis, the only
      significant predictor of progression to ESRD was serum creatinine >2.5 mg/dl at
      biopsy (P = 0. 008). In conclusion, lithium nephrotoxicity primarily targets
      distal and collecting tubules, with a higher incidence of proteinuria and
      associated glomerular pathology than recognized previously. Renal dysfunction is
      often irreversible despite lithium withdrawal, and early detection is essential
      to prevent progression to ESRD.

PMID- 10906158
TI  - Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter
      syndrome.
AB  - ABSTRACT.: Inherited hypokalemic renal tubulopathies are differentiated into at
      least three clinical subtypes: (1) the Gitelman variant of Bartter syndrome (GS);
      (2) hyperprostaglandin E syndrome, the antenatal variant of Bartter syndrome
      (HPS/aBS); and (3) the classic Bartter syndrome (cBS). Hypokalemic metabolic
      alkalosis and renal salt wasting are the common characteristics of all three
      subtypes. Hypocalciuria and hypomagnesemia are specific clinical features of
      Gitelman syndrome, while HPS/aBS is a life-threatening disorder of the newborn
      with polyhydramnios, premature delivery, hyposthenuria, and nephrocalcinosis. The
      Gitelman variant is uniformly caused by mutations in the gene for the thiazide
      sensitive NaCl-cotransporter NCCT (SLC12A3) of the distal tubule, while HPS/aBS
      is caused by mutations in the gene for either the furosemide-sensitive NaK-2Cl
      cotransporter NKCC2 (SLC12A1) or the inwardly rectifying potassium channel ROMK
      (KCNJ1). Recently, mutations in a basolateral chloride channel CLC-Kb (CLCNKB)
      have been described in a subset of patients with a Bartter-like phenotype
      typically lacking nephrocalcinosis. In this study, the screening for CLCNKB
      mutations showed 20 different mutations in the affected children from 30
      families. The clinical characterization revealed a highly variable phenotype
      ranging from episodes of severe volume depletion and hypokalemia during the
      neonatal period to almost asymptomatic patients diagnosed during adolescence.
      This study adds 16 novel mutations to the nine already described, providing
      further evidence that mutations in the gene for the basolateral chloride channel
      CLC-Kb are the molecular basis of classic Bartter syndrome. Interestingly, the
      phenotype elicited by CLCNKB mutations occasionally includes HPS/aBS, as well as
      a Gitelman-like phenotype.

PMID- 10906159
TI  - Characterization of renal chloride channel (CLCN5) mutations in Dent's disease.
AB  - Dent's disease is an X-linked renal tubular disorder characterized by low
      molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis,
      and renal failure. The disease is caused by mutations in a renal chloride channel
      gene, CLCN5, which encodes a 746 amino acid protein (CLC-5), with 12 to 13
      transmembrane domains. In this study, an additional six unrelated patients with
      Dent's disease were identified and investigated for CLCN5 mutations by DNA
      sequence analysis of the 11 coding exons of CLCN5. This revealed six mutations:
      four frameshift deletions involving codons 392, 394, 658, and 728, one nonsense
      mutation (Tyr617Stop), and an A to T transversion at codon 601 that would result
      in either a missense mutation (Asp601Val) or creation of a novel donor splice
      site. These mutations were confirmed by restriction endonuclease or sequence
      specific oligonucleotide hybridization analysis and were not common
      polymorphisms. The frameshift deletions and nonsense mutation predict truncated
      and inactivated CLC-5. The effects of the putative missense Asp601Val mutant CLC
      5 were assessed by heterologous expression in Xenopus oocytes, and this revealed
      a chloride conductance that was similar to that observed for wild-type CLC-5.
      However, an analysis of the mutant CLCN5 transcripts revealed utilization of the
      novel donor splice site, resulting in a truncated CLC-5. Thus, all of the six
      mutations are likely to result in truncated CLC-5 and a loss of function, and
      these findings expand the spectrum of CLCN5 mutations associated with Dent's
      disease.

PMID- 10906161
TI  - Retinoic acid reduces glomerular injury in a rat model of glomerular damage.
AB  - ABSTRACT.: In the reaction of kidneys to injury, cytokine-driven proliferation
      plays an important role and precedes the development of glomerulosclerosis. There
      is great interest in agents that may interfere with such proliferation.
      Therefore, a rat model of mesangioproliferative glomerulonephritis (induced by
      anti-Thy1.1) was studied, and the effects of all-trans-retinoic acid (all-trans
      RA) and isotretinoin, powerful antiproliferative and anti-inflammatory
      substances, on glomerular damage and cell proliferation were examined. Vehicle
      injected control rats were compared with rats treated with daily subcutaneous
      injections of 10 mg/kg body wt all-trans-RA or 40 mg/kg body wt isotretinoin (n =
      9 to 11 per group), using either a pretreatment (days -2 through 8) or
      posttreatment (days +3 through +8) protocol, i.e., starting before or after the
      induction of anti-Thy1.1 nephritis, respectively. All-trans-RA prevented the BP
      increase evoked by anti-Thy1.1 (anti-Thy1.1/vehicle, 112.2 +/- 4.8 mmHg; anti
      Thy1.1/RA, 87.5 +/- 2. 5 mmHg; P < 0.001). Treatment with all-trans-RA or
      isotretinoin produced a 70% decrease in the urinary albumin excretion rate (P <
      0. 02). Periodic acid-Schiff staining of saline-perfused kidneys (day 8) revealed
      significantly fewer glomerular cells in RA-treated nephritic rats (anti
      Thy1.1/vehicle, 97 +/- 3.1 cells/glomerulus; anti-Thy1.1/RA, 80 +/- 4.4; P <
      0.02; control/vehicle, 69 +/- 1.2). No difference was observed between all-trans
      RA and isotretinoin treatment. The capillary occlusion scores were significantly
      lower for the anti-Thy1.1/RA-treated group (1.9 +/- 0.1) than for the anti
      Thy1.1/vehicle-treated group (2.9 +/- 0.5, P < 0.001). In the anti-Thy1.1/vehicle
      treated group, 11.9 +/- 1.1 glomerular cells were proliferating cell nuclear
      antigen-positive; however, in the anti-Thy1.1/RA-treated group, only 5.3 +/- 0.8
      cells were proliferating cell nuclear antigen-positive (P < 0.002; control, 2.2
      +/- 0.2). Glomerular mitoses were reduced by 67% in the anti-Thy1. 1/RA-treated
      group, compared with the anti-Thy1.1/control group (P < 0.002). Glomerular
      staining for platelet-derived growth factor B-chain was significantly reduced in
      anti-Thy1.1-treated nephritic rats in the presence of isotretinoin or all-trans
      RA, compared with the vehicle-treated group (P < 0.001). It is concluded that all
      trans-RA limits glomerular proliferation, glomerular lesions, and albuminuria in
      an established model of renal damage. The findings point to retinoids as
      potential novel modulators of glomerular injury.

PMID- 10906160
TI  - Effects of low dose sympathetic inhibition on glomerulosclerosis and albuminuria
      in subtotally nephrectomized rats.
AB  - ABSTRACT.: A potential role of the sympathetic nervous system in progression of
      renal failure has received little attention. This study examined whether
      nonhypotensive doses of moxonidine, an agent that reduces sympathetic activity,
      affects glomerulosclerosis, urine albumin excretion, and indices of renal
      handling of norepinephrine (NE) in subtotally nephrectomized (SNX) rats. Sprague
      Dawley rats were SNX or sham-operated (control). SNX rats were either left
      untreated or treated with moxonidine in a dose (1.5 mg/kg body wt per d) that did
      not modify telemetrically monitored 24-h BP. Glomerular and renal morphology were
      evaluated by quantitative histology, immunohistochemistry, and in situ
      hybridization. Urine albumin excretion rate was analyzed by enzyme-linked
      immunosorbent assay, and kidney angiotensin II and NE content were measured using
      HPLC, (3)H-NE uptake, and release. Body and kidney weight and BP were not
      significantly different between SNX with or without moxonidine. The
      glomerulosclerosis index was significantly lower in moxonidine-treated (0.88 +/-
      0.09) compared with untreated (1.55 +/- 0.28) SNX rats, as was the index of
      vascular damage (0.32 +/- 0.14 versus 0.67 +/- 0.16). The number of proliferating
      cell nuclear antigen-positive glomerular and tubular cells per area was
      significantly higher in untreated SNX rats than in controls and moxonidine
      treated SNX rats. The same was true for urine albumin excretion rate. Renal
      angiotensin II tissue concentration was not affected by moxonidine. In untreated
      SNX rats, renal nerve stimulation and exogenous NE induced an increase in
      isolated kidney perfusion pressure (102 +/- 21 versus 63 +/- 8 mmHg). Renal
      endogenous NE content was significantly lower in SNX rats than in controls (86 +/
      14 versus 140 +/- 17 pg/mg wet weight). Cortical uptake of [(3)H]-NE was not
      different, but cortical NE release was significantly higher in SNX rats than in
      controls. Reduced function of presynaptic inhibitory alpha-adreno-receptors is
      unlikely because an alpha(2)-adrenoceptor antagonist increased NE release. At
      subantihypertensive doses, moxonidine ameliorates renal structural and functional
      damage in SNX animals, possibly through central inhibition of efferent
      sympathetic nerve traffic. In kidneys of SNX rats, indirect evidence was found
      for increased activity of a reduced number of nerve fibers.

PMID- 10906162
TI  - Food restriction prevents advanced glycation end product accumulation and retards
      kidney aging in lean rats.
AB  - ABSTRACT.: Tissue content of advanced glycation end products (AGE) increases with
      age and contributes to the changes in structure and function of the renal and
      cardiovascular systems. The effect of chronic food restriction on this AGE
      accumulation was investigated in lean WAG/Rij rats. A 30% food restriction
      performed from 10 to 30 mo in female rats reduced their mean body weight from 240
      +/- 7 to 160 +/- 12 g, but did not modify their survival. AGE collagen content
      increased from 14.3 +/- 5.5 to 104.7 +/- 13.0 arbitrary units per microgram
      (AU/microg) of hydroxyproline (OHPro) in kidney between 10 and 30 mo, and from
      9.7 +/- 1.2 to 310.6 +/- 34.6 AU/microg OHPro in the abdominal aorta. Food
      restriction reduced AGE accumulation to 21.4 +/- 3.3 and 74.6 +/- 16.5 AU/microg
      OHPro in kidney and aorta of 30-mo-old animals. Similar results were found for
      collagen prepared from isolated glomeruli (7.8 +/- 1.2, 81.2 +/- 16.1, and 10.3
      +/- 4.3 AU/microg OHPro in 10-mo, 30-mo, and restricted 30-mo-old rats).
      Reduction of intrarenal and arterial AGE accumulation by food restriction was
      confirmed by immunostaining in optical microscopy. Age-related changes in
      arterial and kidney structures as polyuria and proteinuria were mainly prevented
      by food restriction. These data indicate that chronic food restriction reduces
      the accumulation of AGE and preserves the structure and function of the renal and
      cardiovascular systems in learn rats, although it did not affect survival of the
      animals between 10 and 30 mo.

PMID- 10906163
TI  - Selective ET(A) receptor antagonism with ABT-627 attenuates all renal effects of
      endothelin in humans.
AB  - ++Endothelin (ET-1) acts as a potent vasoconstrictor in the human kidney, and
      this vasoconstriction could contribute to the ischemia seen in acute renal
      failure. In animal studies, the vasoactive properties of ET-1 are known to be
      ET(A) receptor-and/or ET(B) receptor-mediated; however, the receptor subtype
      involved in the human kidney remains to be defined. In a phase I, single-center,
      double-blind, randomized, three-period, crossover design, the effects of orally
      administered ABT-627, a selective ET(A) receptor antagonist, on renal
      hemodynamics during ET-1 infusion were evaluated. Two doses of ABT-627 (5 and 20
      mg) were compared with placebo and nifedipine. For each dose level of ABT-627, a
      cohort of nine subjects was studied. A para-aminohippuric acid/inulin clearance
      test was performed once at the end of each 7-d treatment period. Infusion of ET-1
      significantly decreased effective renal plasma flow, GFR, sodium excretion, and
      urine flow. Pretreatment with 20 mg of ABT-627 significantly decreased mean
      arterial pressure. In contrast, 7 d of treatment with both doses of ABT-627 did
      not affect baseline renal parameters. However, because mean arterial pressure
      decreased, a tendency toward a reduction of renal vascular resistance could
      indeed be demonstrated. Compared with placebo, both doses of ABT-627 were equally
      effective in blocking all renal effects caused by ET-1 infusion. In the model of
      exogenous ET-1 infusion, ABT-627 had a tendency to prevent ET-1-induced renal
      changes more effectively compared with nifedipine. The contribution of endogenous
      ET-1 and the ET(A) receptor in maintaining basal renal vascular tone in the human
      kidney is small. In addition, compared with placebo, selective ET(A) receptor
      antagonism with both doses of ABT-627 completely prevented all renal changes
      caused by ET-1 infusion.

PMID- 10906165
TI  - Energy transfer is the single most important factor for the difference in
      vascular response between isolated ultrafiltration and hemodialysis.
AB  - Differences in vascular reactivity between isolated ultrafiltration (i-UF) and
      hemodialysis (UF + HD) have been attributed to various factors, including
      differences in core temperature (CT) and energy transfer (ET). However, the
      relative importance of these thermal factors is not known. The aim of this study
      was to elucidate to what extent differences in ET are responsible for the
      divergent vascular response between i-UF and UF + HD. During four different
      dialysis treatments in 15 patients, four measurements were performed that
      consisted of 1 h of i-UF, UF + HD at a dialysate temperature (T(d)) of 37.5
      degrees C (UF + HD(37.5)), UF + HD at T(d) 35.5 degrees C (UF + HD(35.5)), and UF
      + HD with a similar ET as during i-UF(UF + HD(ET-set)). The UF rate in all
      sessions was 1 L/h. CT ( degrees C) decreased significantly during i-UF and UF +
      HD(ET-set) (P < 0.05), increased significantly during UF + HD(37.5) (P < 0.05),
      and remained unchanged during UF + HD(35. 5) (NS). Forearm vascular reactivity
      increased significantly during i-UF, UF + HD(ET-set), and UF + HD(35.5) (P <
      0.05), but not during UF + HD(37.5) (NS). Venous tone increased significantly
      during i-UF, UF + HD(35.5), and UF + HD(ET-set) (P < 0.05), and decreased
      significantly during UF + HD(37.5) (P < 0.05). When i-UF and UF + HD are matched
      for ET, all differences in vascular response disappear, showing that differences
      in ET are the single most important factor for the observed difference in
      vascular response between i-UF and UF + HD. In contrast to UF + HD(37.5),
      vascular reactivity was improved when the increase in CT was prevented during UF
      + HD(35.5) and appeared to increase more when CT was lowered. Preventing the
      increase in CT during UF + HD appears to be mandatory for optimization of
      hemodynamic stability during dialysis.

PMID- 10906164
TI  - Quantification and longitudinal trends of kidney, renal cyst, and renal
      parenchyma volumes in autosomal dominant polycystic kidney disease.
AB  - ABSTRACT.: The aims of this study were to assess the accuracy and reproducibility
      of volumetric determinations of total kidney, renal cyst, and renal parenchymal
      volumes, using fast electron-beam computerized tomography scanning, and to
      determine the rate of change of these volumes. Nine patients with autosomal
      dominant polycystic kidney disease (ADPKD) and serum creatinine < or = 1.3 mg/dl
      and/or an initial iothalamate clearance > or = to 60 ml/min per 1.73 m(2) were
      imaged weekly over a 3-wk period (total of 3 times). Approximately 8 yr later,
      they returned for follow-up studies. The kidney volume estimation technique
      involved a manual segmentation (perimeter drawing) of the kidneys and a
      semiautomatic threshold approach, using a histogram analysis of the peak
      densities of renal parenchyma and renal cysts. At entry, total kidney and renal
      cyst volumes correlated positively with age, while renal parenchymal volumes and
      GFR correlated negatively with age. The average coefficient of variation values
      for the three initial consecutive measurements of total kidney, renal cyst
      (actual and as a percent of total volume), and renal parenchymal volume were 3.4,
      7.2, 5.3, and 5.6%, respectively. During the 8 yr of follow-up, total kidney and
      renal cyst volumes increased, while renal parenchymal volumes and GFR declined.
      The rate of increase in total kidney and renal cyst volumes varied markedly from
      patient to patient. There was a significant correlation between rate of increase
      in renal cyst volume and the rate of decline in GFR. The patients with an initial
      urine protein/osmolality ratio >0.13 mg/L per mosmol per kg had a significantly
      higher increase in renal volume and decline in GFR than those with a lower ratio.
      In summary, the results of this pilot study suggest that: (1) electron-beam
      computerized tomography is capable of measuring total kidney, renal cyst, and
      renal parenchymal volumes reproducibly; (2) total kidney and renal cyst volumes
      increase, while parenchymal volumes decrease with time; (3) the increase in cyst
      volume correlates best with the decline in renal function; and (4) renal volumes
      appear to be good surrogate markers for disease progression in ADPKD.

PMID- 10906166
TI  - Dyadic relationship conflict, gender, and mortality in urban hemodialysis
      patients.
AB  - The effects of dyadic satisfaction and conflict have not been well defined in the
      hemodialysis (HD) population. The aim of this study was to determine whether the
      perception of decreased dyadic satisfaction was associated with mortality in
      patients treated with HD, and if so, whether there were different relationships
      between risk factors, and differential outcomes in men and women. A total of 174
      HD patients, primarily African-Americans, involved in dyadic relationships for
      more than 6 mo had indices of dyadic satisfaction, depression, perception of
      illness effects, social support, behavioral compliance with the dialysis
      prescription, and plasma interleukin-1 (IL-1) and beta-endorphin levels measured.
      Cox proportional hazards models assessed relative mortality risks. Patients'
      dyadic satisfaction scores correlated with beta-endorphin levels. There was no
      correlation of IL-1 or beta-endorphin with any psychosocial or behavioral
      compliance measure in the group as a whole. Correlations between psychosocial,
      medical, and neuroimmunologic variables were different in men and women. For
      women, dyadic satisfaction correlated with beta-endorphin levels, depression, and
      perception of illness. Women with higher dyadic satisfaction and decreased dyadic
      conflict were at decreased mortality risk, but dyadic adjustment indices were
      unassociated with differential survival in the larger group of men. Correlations
      between neuroendocrine and immune markers are different in African-American male
      and female HD patients. Greater dyadic satisfaction and lower dyadic conflict are
      independently associated with decreased mortality in female African-American HD
      patients, of the same order of magnitude as medical risk factors. Such effects
      may be attributable to a relationship between dyadic satisfaction and conflict
      and health-related behaviors, or through an effect on neuroendocrine or
      immunologic status.

PMID- 10906167
TI  - Length of stay and costs for hospitalized hemodialysis patients: nephrologists
      versus internists.
AB  - The high cost of hospitalization for hemodialysis patients has become a major
      health care issue. To address this issue, length of hospital stay and costs for
      these patients were compared with services covered by nephrologists and services
      covered by internists. Hemodialysis patients (n = 161) were prospectively
      admitted 219 times on alternate days to services covered by nephrologists or by
      internists from July 1995 to March 1996. Admissions to nonmedical services and
      admissions for overnight observation were excluded. Length of stay, costs, and
      risk-adjusted predicted length of stay and costs, as well as the number of
      consultations were compared between services, using Wilcoxon rank sum tests.
      Readmissions and deaths were compared using chi(2) tests. Mean length of stay for
      admissions to the nephrology service (n = 114) was 6.3 days compared with 8.1
      days for admissions to internal medicine services (n = 105) (P = 0.017). The
      predicted length of stay was similar. Mean overall cost for admissions under the
      care of nephrologists was $7,925 versus $10,773 under the care of internists (P =
      0.101). The internal medicine service averaged 1.5 consultations versus 0.5
      consultations for the nephrology service (P = 0.001). The risk of readmission was
      24% for nephrologists and 30% for internists (P = 0.328). Death within 90 days of
      discharge was 12% for the nephrology group and 22% for the internal medicine
      group (P = 0.07). The length of stay was significantly shorter for hemodialysis
      patients under the care of nephrologists compared with internists. The average
      total costs and risk of readmissions tended to be lower for nephrologists. If
      these results are corroborated, the care of hemodialysis patients by the
      nephrologist could diminish the overall expense of the ESRD program.

PMID- 10906169
TI  - Gene therapy for lysosomal storage disorders with neuropathology.

PMID- 10906168
TI  - A new anti-inflammatory compound, FR167653, ameliorates crescentic
      glomerulonephritis in Wistar-Kyoto rats.
AB  - The pathophysiologic effects of FR167653 were investigated in a model of
      crescentic glomerulonephritis induced by a small dose of nephrotoxic serum in
      Wistar-Kyoto rats. The rats developed crescentic glomerulonephritis by 6 d after
      the administration of serum. The subcutaneous administration of FR167653 (32
      mg/kg) markedly decreased the severity of the renal damage. In a group of rats
      treated with FR167653 daily from day 0 to day 6, glomerular damage, including
      crescent formation and proteinuria, was virtually absent. FR167653 markedly
      decreased urinary levels of monocyte chemoattractant protein-1 (MCP-1). In
      addition, FR167653 reduced production of MCP-1 protein and transcripts in the
      diseased kidneys. In a group of rats for which treatment was initiated on day 3,
      shortly after the appearance of glomerular abnormalities, the progression of
      renal disease was appreciably retarded, with partial inhibition of MCP-1. In
      contrast, when rats were treated only on the first day, no beneficial effects
      were observed and severe proliferative and necrotizing glomerulonephritis, with
      crescent formation, was induced by day 6, with the upregulation of MCP-1. These
      results suggest that FR167653 may be effective against crescentic
      glomerulonephritis, possibly via the inhibition of MCP-1. In addition, there was
      marked reduction in renal injury even when FR167653 treatment was initiated after
      glomerular inflammation was established, suggesting that the therapeutic
      application of FR167653 may be clinically useful for human renal diseases.

PMID- 10906170
TI  - 1999 ASN Presidential Address.

PMID- 10906171
TI  - Rhabdomyolysis.

PMID- 10906172
TI  - Human immunodeficiency virus and AIDS: insights from animal lentiviruses.

PMID- 10906173
TI  - Innate immune response of the human host to exposure with herpes simplex virus
      type 1: in vitro control of the virus infection by enhanced natural killer
      activity via interleukin-15 induction.
AB  - Infections with herpes simplex virus type 1 (HSV-1) in humans and in animal
      models are accompanied by enhanced natural killer (NK) activity. In vitro, HSV-1
      also enhances the NK activity of human peripheral blood mononuclear cells (PBMC).
      The molecular basis of this enhanced NK activity, however, is not well
      characterized. We investigated the role of human interleukin-15 (IL-15) in this
      phenomenon and report here that HSV-1-mediated enhanced NK activity was abrogated
      by neutralizing antibodies for IL-15 but not for other cytokines (i.e., IL-2, IL
      12, gamma interferon [IFN-gamma], tumor necrosis factor alpha, or IFN-alpha).
      Anti-CD122 antibodies which block signaling through IL-2 receptor beta chain, and
      therefore neutralize the effects of IL-15 (and IL-2), also abrogated this
      enhancement. Furthermore, HSV-1 increased the levels of IL-15 mRNA and the
      production of IL-15 in HSV-1-infected PBMC cultures. The neutralization of IL-15
      in cocultures of PBMC with HSV-1-infected cells significantly increased HSV-1
      production. These results strongly suggest a role for IL-15 in the HSV-1-mediated
      in vitro enhancement of NK activity and in the PBMC-mediated suppression of HSV-1
      replication.

PMID- 10906174
TI  - Origin of hepatitis delta virus mRNA.
AB  - Hepatitis delta virus (HDV) is unique relative to all known animal viruses,
      especially in terms of its ability to redirect host RNA polymerase(s) to
      transcribe its 1,679-nucleotide (nt) circular RNA genome. During replication
      there accumulates not only more molecules of the genome but also its exact
      complement, the antigenome. In addition, there are relatively smaller amounts of
      an 800-nt RNA of antigenomic polarity that is polyadenylated and considered to
      act as mRNA for translation of the single and essential HDV protein, the delta
      antigen. Characterization of this mRNA could provide insights into the in vivo
      mechanism of HDV RNA-directed RNA transcription and processing. Previously, we
      showed that the 5' end of this RNA was located in the majority of species, at nt
      1630. The present studies show that (i) at least some of this RNA, as extracted
      from the liver of an HDV-infected woodchuck, behaved as if it contained a 5'-cap
      structure; (ii) in the infected liver there were additional polyadenylated
      antigenomic HDV RNA species with 5' ends located at least 202 nt and even 335 nt
      beyond the nt 1630 site, (iii) the 5' end at nt 1630 was not detected in
      transfected cells, following DNA-directed HDV RNA transcription, in the absence
      of genome replication, and (iv) nevertheless, using in vitro transcription with
      purified human RNA polymerase II holoenzyme and genomic RNA template, we did not
      detect initiation of template-dependent RNA synthesis; we observed only low
      levels of 3'-end addition to the template. These new findings support the
      interpretation that the 5' end detected at nt 1630 during HDV replication
      represents a specific site for the initiation of an RNA-directed RNA synthesis,
      which is then modified by capping.

PMID- 10906176
TI  - Novel mouse type D endogenous proviruses and ETn elements share long terminal
      repeat and internal sequences.
AB  - The repetitive ETn (early transposon) family of sequences represents an active
      "mobile mutagen" in the mouse genome. The presence of long terminal repeats
      (LTRs) and other diagnostic features indicate that ETns are retrotransposons but
      they contain no long open reading frames or documented similarity to the genes of
      known retroviruses or other retroelements. Thus, the mechanisms responsible for
      the mobility of this family have been unknown. In this study, we used computer
      searches to detect a small region of previously unrecognized type D retroviral
      pol homology within ETn elements. This small region was used to isolate two mouse
      endogenous proviral elements with gag, pro, and pol genes similar to simian type
      D viruses. This new family of mouse endogenous proviruses, termed MusD, is
      present in several hundred copies in the genome. Interestingly, the MusD LTRs, 3'
      internal region, and the 5' region expected to contain the packaging signal are
      very closely related to members of the ETn subfamily that have recently
      transposed. Analysis of different mouse strains indicates that MusD elements
      predate the existence of the mobile subfamily of ETns. These findings indicate
      that the ETn family was likely created via recombination events resulting in a
      near complete substitution of MusD coding sequences with unrelated DNA.
      Furthermore, these results suggest that ETn transcripts retrotranspose using
      proteins provided by MusD proviruses.

PMID- 10906175
TI  - Lentivirus infection in the brain induces matrix metalloproteinase expression:
      role of envelope diversity.
AB  - Infection of the brain by lentiviruses, including human immunodeficiency virus
      (HIV) and feline immunodeficiency virus (FIV), causes inflammation and results in
      neurodegeneration. Molecular diversity within the lentivirus envelope gene has
      been implicated in the regulation of cell tropism and the host response to
      infection. Here, we examine the hypothesis that envelope sequence diversity
      modulates the expression of host molecules implicated in lentivirus-induced brain
      disease, including matrix metalloproteinases (MMP) and related transcription
      factors. Infection of primary macrophages by chimeric HIV clones containing brain
      derived envelope fragments from patients with HIV-associated dementia (HAD) or
      nondemented AIDS patients (HIV-ND) showed that MMP-2 and -9 levels in conditioned
      media were significantly higher for the HAD clones. Similarly, STAT-1 and JAK-1
      levels were higher in macrophages infected by HAD clones. Infections of primary
      feline macrophages by the neurovirulent FIV strain (V(1)CSF), the less
      neurovirulent strain (Petaluma), and a chimera containing the V(1)CSF envelope in
      a Petaluma background (FIV-Ch) revealed that MMP-2 and -9 levels were
      significantly higher in conditioned media from V(1)CSF- and FIV-Ch-infected
      macrophages, which was associated with increased intracellular STAT-1 and JAK-1
      levels. The STAT-1 inhibitor fludarabine significantly reduced MMP-2 expression,
      but not MMP-9 expression, in FIV-infected macrophages. Analysis of MMP mRNA and
      protein levels in brain samples from HIV-infected persons or FIV-infected cats
      showed that MMP-2 and -9 levels were significantly increased in lentivirus
      infected brains compared to those of uninfected controls. Elevated MMP expression
      was accompanied by significant increases in STAT-1 and JAK-1 mRNA and protein
      levels in the same brain samples. The present findings indicate that two
      lentiviruses, HIV and FIV, have common mechanisms of MMP-2 and -9 induction,
      which is modulated in part by envelope sequence diversity and the STAT-1/JAK-1
      signaling pathway.

PMID- 10906178
TI  - Mapping and characterization of the N-terminal I domain of human immunodeficiency
      virus type 1 Pr55(Gag).
AB  - Human immunodeficiency virus (HIV) type 1 particles assemble at the plasma
      membrane of cells in a manner similar to that of the type C oncoretroviruses. The
      Pr55(Gag) molecule directs the assembly process and is sufficient for particle
      assembly in the absence of all other viral gene products. The I domain is an
      assembly domain that has been previously localized to the nucleocapsid (NC)
      region of Gag. In this study we utilized a series of Gag-green fluorescent
      protein (GFP) fusion proteins to precisely identify sequences that constitute the
      N-terminal I domain of Pr55(Gag). The minimal sequence required for the I domain
      was localized to the extreme N terminus of NC. Two basic residues (arginine 380
      and arginine 384) within the initial seven residues of NC were found to be
      critical for the function of the N-terminal I domain. The presence of positive
      charge alone in these two positions, however, was not sufficient to mediate the
      formation of dense Gag particles. The I domain was required for the formation of
      detergent-resistant complexes of Gag protein, and confocal microscopy
      demonstrated that the I domain was also required for the formation of punctate
      foci of Gag proteins at the plasma membrane. Electron microscopic analysis of
      cells expressing Gag-GFP fusion constructs with an intact I domain revealed
      numerous retrovirus-like particles (RVLPs) budding from the plasma membrane,
      while I domain-deficient constructs failed to generate visible RVLPs. These
      results provide evidence that Gag-Gag interactions mediated by the I domain play
      a central role in the assembly of HIV particles.

PMID- 10906177
TI  - The human cytomegalovirus 86-kilodalton major immediate-early protein interacts
      physically and functionally with histone acetyltransferase P/CAF.
AB  - The major immediate-early proteins of human cytomegalovirus (HCMV) play a pivotal
      role in controlling viral and cellular gene expression during productive
      infection. As well as negatively autoregulating its own promoter, the HCMV 86-kDa
      major immediate early protein (IE86) activates viral early gene expression and is
      known to be a promiscuous transcriptional regulator of cellular genes. IE86
      appears to act as a multimodal transcription factor. It is able to bind directly
      to target promoters to activate transcription but is also able to bridge between
      upstream binding factors such as CREB/ATF and the basal transcription complex as
      well as interacting directly with general transcription factors such as TATA
      binding protein and TFIIB. We now show that IE86 is also able to interact
      directly with histone acetyltransferases during infection. At least one of these
      factors is the histone acetyltransferase CBP-associated factor (P/CAF).
      Furthermore, we show that this interaction results in synergistic transactivation
      by IE86 of IE86-responsive promoters. Recruitment of such chromatin-remodeling
      factors to target promoters by IE86 may help explain the ability of this viral
      protein to act as a promiscuous transactivator of cellular genes.

PMID- 10906179
TI  - Infectivity of Moloney murine leukemia virus defective in late assembly events is
      restored by late assembly domains of other retroviruses.
AB  - The p12 region of the Moloney murine leukemia virus (M-MuLV) Gag protein contains
      a PPPY motif important for efficient virion assembly and release. To probe the
      function of the PPPY motif, a series of insertions of homologous and heterologous
      motifs from other retroviruses were introduced at various positions in a mutant
      gag gene lacking the PPPY motif. The assembly defects of the PPPY deletion mutant
      could be rescued by insertion of a wild-type PPPY motif and flanking sequences at
      several ectopic positions in the Gag protein. The late assembly domain (L-domain)
      of Rous sarcoma virus (RSV) or human immunodeficiency virus type 1 (HIV-1) could
      also fully or partially restore M-MuLV assembly when introduced into matrix, p12,
      or nucleocapsid domains of the mutant M-MuLV Gag protein lacking the PPPY motif.
      Strikingly, mutant viruses carrying the RSV or the HIV-1 L-domain at the original
      location of the deleted PPPY motif were replication competent in rodent cells.
      These data suggest that the PPPY motif of M-MuLV acts in a partially position
      independent manner and is functionally interchangeable with L-domains of other
      retroviruses. Electron microscopy studies revealed that deletion of the entire
      p12 region resulted in the formation of tube-like rather than spherical
      particles. Remarkably, the PPPY deletion mutant formed chain structures composed
      of multiple viral particles linked on the cell surface. Many of the mutants with
      heterologous L-domains released virions with wild-type morphology.

PMID- 10906180
TI  - Differential transcription attenuation of rabies virus genes by intergenic
      regions: generation of recombinant viruses overexpressing the polymerase gene.
AB  - Gene expression of nonsegmented negative-sense RNA viruses involves sequential
      synthesis of monocistronic mRNAs and transcriptional attenuation at gene borders
      resulting in a transcript gradient. To address the role of the heterogeneous
      rabies virus (RV) intergenic regions (IGRs) in transcription attenuation, we
      constructed bicistronic model RNAs in which two reporter genes are separated by
      the RV N/P gene border. Replacement of the 2-nucleotide (nt) N/P IGR with the 5
      nt IGRs from the P/M or M/G border resulted in attenuation of downstream gene
      transcription to 78 or 81%, respectively. A severe attenuation to 11% was
      observed for the 24-nt G/L border. This indicated that attenuation in RV is
      correlated with the length of the IGR, and, in particular, severe downregulation
      of the L (polymerase) gene by the 24 nt IGR. By reverse genetics, we recovered
      viable RVs in which the strongly attenuating G/L gene border of wild-type (wt) RV
      (SAD L16) was replaced with N/P-derived gene borders (SAD T and SAD T2). In these
      viruses, transcription of L mRNA was enhanced by factors of 1.8 and 5.1,
      respectively, resulting in exaggerated general gene expression, faster growth,
      higher virus titers, and induction of cytopathic effects in cell culture. The
      major role of the IGR in attenuation was further confirmed by reintroduction of
      the wt 24-nt IGR into SAD T, resulting in a ninefold drop of L mRNA. The ability
      to modulate RV gene expression by altering transcriptional attenuation is an
      advantage in the study of virus protein functions and in the development of gene
      delivery vectors.

PMID- 10906181
TI  - Overexpression of p21(waf1) in human T-cell lymphotropic virus type 1-infected
      cells and its association with cyclin A/cdk2.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell
      leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP). T-cell transformation is mainly due to the actions of the viral
      phosphoprotein Tax. Tax interacts with multiple transcriptional factors, aiding
      the transcription of many cellular genes. Here, we report that the cyclin
      dependent kinase inhibitor p21/waf1 is overexpressed in all HTLV-1-infected cell
      lines tested as well as in ATL and HAM/TSP patient samples. Tax was found to be
      able to transactivate the endogenous p21/waf1 promoter, as detected by RNase
      protection, as well as activate a series of wild-type and 5'-deletion constructs
      linked to a luciferase reporter cassette. Wild-type but not a mutant form of Tax
      (M47) transactivated the p21/waf1 promoter in a p53-independent manner and
      utilized a minimal promoter that contained E2A and TATA box sequences. The
      p21/waf1 protein was reproducibly observed to be complexed with cyclin A/cdk2 and
      not with any other known G(1), S, or G(2)/M cyclins. Functionally, the
      association of p21/cyclin A/cdk2 decreased histone H1 phosphorylation in vitro,
      as observed in immunoprecipitations followed by kinase assays, and affected other
      substrates, such as the C terminus of Rb protein involved in c-Abl and histone
      deacetylase-1 (HDAC1) regulation. Interestingly, upon the use of a stress signal,
      such as gamma-irradiation, we found that the p21/cyclin A/cdk2 complex was able
      to block all known phosphorylation sites on the Rb molecule. Finally, using
      elutriated cell cycle fractions and a stress signal, we observed that the HTLV-1
      infected T cells containing wild-type Tax, which had been in early or mid-G(1)
      phase prior to gamma-irradiation, arrested in G(1) and did not undergo apoptosis.
      This may be an important mechanism for an oncogenic virus such as HTLV-1 to stop
      the host at the G(1)/S boundary and to repair the damaged DNA upon injury, prior
      to S-phase entry.

PMID- 10906182
TI  - Leaky scanning is the predominant mechanism for translation of human
      papillomavirus type 16 E7 oncoprotein from E6/E7 bicistronic mRNA.
AB  - Human papillomaviruses (HPV) are unique in that they generate mRNAs that
      apparently can express multiple proteins from tandemly arranged open reading
      frames. The mechanisms by which this is achieved are uncertain and are at odds
      with the basic predictions of the scanning model for translation initiation. We
      investigated the unorthodox mechanism by which the E6 and E7 oncoproteins from
      human papillomavirus type 16 (HPV-16) can be translated from a single,
      bicistronic mRNA. The short E6 5' untranslated region (UTR) was shown to promote
      translation as efficiently as a UTR from Xenopus beta-globin. Insertion of a
      secondary structural element into the UTR inhibited both E6 and E7 expression,
      suggesting that E7 expression depends on ribosomal scanning from the 5' end of
      the mRNA. E7 translation was found to be cap dependent, but E6 was more dependent
      on capping and eIF4F activity than E7. Insertion of secondary structural elements
      at various points in the region upstream of E7 profoundly inhibited translation,
      indicating that scanning was probably continuous. Insertion of the E6 region
      between Renilla and firefly luciferase genes revealed little or no internal
      ribosomal entry site activity. However when E6 was located at the 5' end of the
      mRNA, it permitted over 100-fold-higher levels of downstream cistron translation
      than did the Renilla open reading frame. Internal AUGs in the E6 region with
      strong or intermediate Kozak sequence contexts were unable to inhibit E7
      translation, but initiation at the E7 AUG was efficient and accurate. These data
      support a model in which E7 translation is facilitated by an extreme degree of
      leaky scanning, requiring the negotiation of 13 upstream AUGs. Ribosomal
      initiation complexes which fail to initiate at the E6 start codon can scan
      through to the E7 AUG without initiating translation, but competence to initiate
      is achieved once the E7 AUG is reached. These findings suggest that the E6 region
      of HPV-16 comprises features that sponsor both translation of the E6 protein and
      enhancement of translation at a downstream site.

PMID- 10906183
TI  - High-efficiency utilization of the bovine integrin alpha(v)beta(3) as a receptor
      for foot-and-mouth disease virus is dependent on the bovine beta(3) subunit.
AB  - We have previously reported that Foot-and-mouth disease virus (FMDV), which is
      virulent for cattle and swine, can utilize the integrin alpha(v)beta(3) as a
      receptor on cultured cells. Since those studies were performed with the human
      integrin, we have molecularly cloned the bovine homolog of the integrin
      alpha(v)beta(3) and have compared the two receptors for utilization by FMDV. Both
      the alpha(v) and beta(3) subunits of the bovine integrin have high degrees of
      amino acid sequence similarity to their corresponding human subunits in the
      ectodomains (96%) and essentially identical transmembrane and cytoplasmic
      domains. Within the putative ligand-binding domains, the bovine and human
      alpha(v) subunits have a 98.8% amino acid sequence similarity while there is only
      a 93% similarity between the beta(3) subunits of these two species. COS cell
      cultures, which are not susceptible to FMDV infection, become susceptible if
      cotransfected with alpha(v) and beta(3) subunit cDNAs from a bovine or human
      source. Cultures cotransfected with the bovine alpha(v)beta(3) subunit cDNAs and
      infected with FMDV synthesize greater amounts of viral proteins than do infected
      cultures cotransfected with the human integrin subunits. Cells cotransfected with
      a bovine alpha(v) subunit and a human beta(3) subunit synthesize viral proteins
      at levels equivalent to those in cells expressing both human subunits. However,
      cells cotransfected with the human alpha(v) and the bovine beta(3) subunits
      synthesize amounts of viral proteins equivalent to those in cells expressing both
      bovine subunits, indicating that the bovine beta(3) subunit is responsible for
      the increased effectiveness of this receptor. By engineering chimeric bovine
      human beta(3) subunits, we have shown that this increase in receptor efficiency
      is due to sequences encoding the C-terminal one-third of the subunit ectodomain,
      which contains a highly structured cysteine-rich repeat region. We postulate that
      amino acid sequence differences within this region may be responsible for
      structural differences between the human and bovine beta(3) subunit, leading to
      more efficient utilization of the bovine receptor by this bovine pathogen.

PMID- 10906184
TI  - Processing of alpha-globin and ICP0 mRNA in cells infected with herpes simplex
      virus type 1 ICP27 mutants.
AB  - Herpes simplex virus (HSV) ICP27 is an essential and multifunctional regulator of
      viral gene expression that modulates RNA splicing, polyadenylation, and nuclear
      export. We have previously reported that ICP27 causes the cytoplasmic
      accumulation of unspliced alpha-globin pre-mRNA. Here we examined the effects of
      a series of ICP27 mutations that alter important functional regions of the
      protein on the processing and nuclear transport of alpha-globin and HSV ICP0 RNA.
      The results demonstrate that ICP27 mutants that are impaired for growth in
      noncomplementing cells, including mutants in the N- and C-terminal regions, are
      defective in the accumulation of alpha-globin pre-mRNA. Unexpectedly, several
      mutants that are competent to repress the expression of reporter genes in
      transient transfection assays failed to accumulate unspliced RNA, implying that
      different mechanisms are responsible for transrepression and pre-mRNA
      accumulation. Several mutants caused a marked increase in the length and
      heterogeneity of the alpha-globin mRNA poly(A) tail, suggesting that ICP27 may
      directly or indirectly affect the regulation of poly(A) polymerase. ICP27 was
      also required for the accumulation of multiple ICP0 intron-bearing transcripts,
      but this effect displayed a mutational sensitivity profile different from that of
      accumulation of unspliced alpha-globin RNA. Moreover, unlike spliced and
      unspliced alpha-globin RNAs, which were efficiently exported to the cytoplasm,
      spliced and intron-containing ICP0 transcripts were predominantly nuclear in
      localization, and ICP27 was not required for nuclear retention of the spliced
      message. We propose that these transcript- and ICP27 allele-specific differences
      may be explained by the presence of a strong cis-acting ICP27 response element in
      the alpha-globin transcript.

PMID- 10906185
TI  - Human immunodeficiency virus-specific circulating CD8 T lymphocytes have down
      modulated CD3zeta and CD28, key signaling molecules for T-cell activation.
AB  - Although human immunodeficiency virus (HIV)-infected subjects without AIDS have a
      high frequency of HIV-specific CD8 T lymphocytes, cellular immunity is unable to
      control infection. Freshly isolated lymphocytes often do not lyse HIV-infected
      targets in 4-h cytotoxicity assays. A large fraction of circulating CD8 T cells
      from HIV-infected donors down-modulate CD3zeta, the signaling component of the T
      cell receptor complex, which is reexpressed in vitro coincident with the return
      of cytotoxic function. To investigate further the link between CD3zeta down
      modulation and possible CD8 T-cell functional defects, we used flow cytometry to
      characterize further the properties of the CD3zeta-down-modulated subset. HIV
      specific CD8 T cells, identified by tetramer staining, are CD3zeta(-). CD8 T
      cells with down-modulated CD3zeta also do not express the key costimulatory
      receptor CD28 and have the cell surface phenotype of activated or memory T cells
      (HLA-DR(+) CD62L(-)). After T-cell activation, CD3zeta-down-modulated cells
      express the activation marker CD69 but not the high-affinity interleukin 2 (IL-2)
      receptor alpha-chain CD25 and produce gamma interferon but not IL-2. Therefore
      HIV-specific CD8 T cells have down-modulated key signaling molecules for T-cell
      activation and costimulation and require exogenous cytokine stimulation. The
      typical impairment of HIV-specific CD4 T helper cells, which would normally
      provide specific CD8 T-cell stimulation, means that in vivo CTL function in vivo
      is compromised in most HIV-infected individuals. In AIDS patients, the functional
      defect is more severe, since CD3zeta is not reexpressed even after IL-2 exposure.

PMID- 10906186
TI  - Analysis of gene expression in a human cell line stably transduced with
      herpesvirus saimiri.
AB  - Herpesvirus saimiri (HVS) is the prototype gamma-2 herpesvirus; it has
      significant homology to the human gammaherpesviruses Kaposi's sarcoma-associated
      virus and Epstein-Barr virus and the murine gammaherpesvirus murine herpesvirus
      68. HVS causes a persistent asymptomatic infection in its natural host, the
      squirrel monkey. Both subgroups A and C possess the ability to immortalize common
      marmoset T lymphocytes to interleukin-2-independent proliferation. However, only
      subgroup C is capable of transforming human, rabbit, and rhesus monkey
      lymphocytes in vitro. In addition, HVS can stably transduce a variety of human
      cell lines where the virus persists as a nonintegrating circular episome. In this
      study, we have developed a system in which the HVS DNA is stably maintained as a
      nonintegrated circular episome in the human lung carcinoma cell line A549. Virus
      production can be reactivated using chemical inducing agents, including
      tetradecanoyl phorbol acetate and n-butyrate, suggesting that the infection in
      human A549 cells is latent. To analyze virus gene expression in these stably
      transduced cells, Northern blot analysis was performed using a series of probes
      produced from restriction fragments spanning the entire coding region of the HVS
      genome. This demonstrated that an adjacent set of genes containing open reading
      frames (ORFs) 71 to 73 are expressed in this stably transduced cell line.
      Moreover, these genes are transcribed as a polycistronic mRNA species produced
      from a common promoter upstream of ORF 73. This model may serve as a useful tool
      in the further analysis of the role of ORFs 71 to 73 in gamma-2 herpesvirus
      latency.

PMID- 10906187
TI  - Viral activation of interleukin-15 (IL-15): characterization of a virus-inducible
      element in the IL-15 promoter region.
AB  - We identified an interferon regulatory factor motif (IRF-E) upstream of an NF
      kappaB binding site in the interleukin-15 (IL-15) promoter. Since these two
      motifs are part of the virus-inducible enhancer region of the beta interferon
      promoter, we speculated that there might be similar responses of these two genes
      to stimuli such as viruses. To test this hypothesis, L929 cells were infected
      with Newcastle disease virus (NDV), which led to the induction of IL-15 mRNA and
      protein expression. Using IL-15 promoter-reporter deletion constructs, a virus
      inducible region, encompassing IRF-E, NF-kappaB, and a 13-nucleotide sequence
      flanked by these two motifs, was mapped to the -295-to--243 position relative to
      the transcription initiation site. Using cotransfection studies, it was
      demonstrated that all three motifs were essential to achieve the maximum promoter
      activity induced by IRF-1 and NF-kappaB expression plasmids. The presence of a
      virus-inducible region in the IL-15 promoter suggests a role for IL-15 as a
      component of host antiviral defense mechanisms.

PMID- 10906188
TI  - Identification of domains of the human papillomavirus type 11 E1 helicase
      involved in oligomerization and binding to the viral origin.
AB  - The E1 helicase of papillomavirus is required, in addition to host cell DNA
      replication factors, during the initiation and elongation phases of viral episome
      replication. During initiation, the viral E2 protein promotes the assembly of
      enzymatically active multimeric E1 complexes at the viral origin of DNA
      replication. In this study we used the two-hybrid system and chemical cross
      linking to demonstrate that human papillomavirus type 11 (HPV11) E1 can self
      associate in yeast and form hexamers in vitro in a reaction stimulated by single
      stranded DNA. Self-association in yeast was most readily detected using
      constructs spanning the E1 C-terminal domain (amino acids 353 to 649) and was
      dependent on a minimal E1-E1 interaction region located between amino acids 353
      and 431. The E1 C-terminal domain was also able to oligomerize in vitro but, in
      contrast to wild-type E1, did so efficiently in the absence of single-stranded
      DNA. Sequences located between amino acids 191 and 353 were necessary for single
      stranded DNA to modulate oligomerization of E1 and were also required, together
      with the rest of the C terminus, for binding of E1 to the origin. Two regions
      within the C-terminal domain were identified as important for oligomerization:
      the ATP-binding domain and region A, which is located within the minimal E1-E1
      interaction domain and is one of four regions of E1 that is highly conserved with
      the large T antigens of simian virus 40 and polyomavirus. Amino acid
      substitutions of highly conserved residues within the ATP-binding domain and
      region A were identified that reduced the ability of E1 to oligomerize and bind
      to the origin in vitro and to support transient DNA replication in vivo. These
      results support the notion that oligomerization of E1 occurs primarily through
      the C-terminal domain of the protein and is allosterically regulated by DNA and
      ATP. The bipartite organization of the E1 C-terminal domain is reminiscent of
      that found in other hexameric proteins and suggests that these proteins may
      oligomerize by a similar mechanism.

PMID- 10906189
TI  - The conserved carboxyl-terminal half of herpes simplex virus type 1 regulatory
      protein ICP27 is dispensable for viral growth in the presence of compensatory
      mutations.
AB  - ICP27 is an essential herpes simplex virus type 1 (HSV-1) immediate-early protein
      that regulates viral gene expression by poorly characterized mechanisms. Previous
      data suggest that its carboxyl (C)-terminal portion is absolutely required for
      productive viral infection. In this study, we isolated M16R, a second-site
      revertant of a viral ICP27 C-terminal mutant. M16R harbors an intragenic
      reversion, as demonstrated by the fact that its cloned ICP27 allele can
      complement the growth of an HSV-1 ICP27 deletion mutant. DNA sequencing
      demonstrated that the intragenic reversion is a frameshift alteration in a
      homopolymeric run of C residues at codons 215 to 217. This results in the
      predicted expression of a truncated, 289-residue molecule bearing 72 novel C
      terminal residues derived from the +1 reading frame. Consistent with this, M16R
      expresses an ICP27-related molecule of the predicted size in the nuclei of
      infected cells. Transfection-based viral complementation assays confirmed that
      the truncated, frameshifted protein can partially substitute for ICP27 in the
      context of viral infection. Surprisingly, its novel C-terminal residues are
      required for this activity. To see if the frameshift mutation is all that is
      required for M16R's viability, we re-engineered the M16R ICP27 allele and
      inserted it into a new viral background, creating the HSV-1 mutant M16exC. An
      additional mutant, exCd305, was constructed which possesses the frameshift in the
      context of an ICP27 gene with the C terminus deleted. We found that both M16exC
      and exCd305 are nonviable in Vero cells, suggesting that one or more extragenic
      mutations are also required for the viability of M16R. Consistent with this
      interpretation, we isolated two viable derivatives of exCd305 which grow
      productively in Vero cells despite being incapable of encoding the C-terminal
      portion of ICP27. Studies of viral DNA synthesis in mutant-infected cells
      indicated that the truncated, frameshifted ICP27 protein can enhance viral DNA
      replication. In summary, our results demonstrate that the C-terminal portion of
      ICP27, conserved widely in herpesviruses and previously believed to be absolutely
      essential, is dispensable for HSV-1 lytic replication in the presence of
      compensatory genomic mutations.

PMID- 10906190
TI  - The large delta antigen of hepatitis delta virus potently inhibits genomic but
      not antigenomic RNA synthesis: a mechanism enabling initiation of viral
      replication.
AB  - Hepatitis delta virus (HDV) contains two types of hepatitis delta antigens (HDAg)
      in the virion. The small form (S-HDAg) is required for HDV RNA replication,
      whereas the large form (L-HDAg) potently inhibits it by a dominant-negative
      inhibitory mechanism. The sequential appearance of these two forms in the
      infected cells regulates HDV RNA synthesis during the viral life cycle. However,
      the presence of almost equal amounts of S-HDAg and L-HDAg in the virion raised a
      puzzling question concerning how HDV can escape the inhibitory effects of L-HDAg
      and initiate RNA replication after infection. In this study, we examined the
      inhibitory effects of L-HDAg on the synthesis of various HDV RNA species. Using
      an HDV RNA-based transfection approach devoid of any artificial DNA
      intermediates, we showed that a small amount of L-HDAg is sufficient to inhibit
      HDV genomic RNA synthesis from the antigenomic RNA template. However, the
      synthesis of antigenomic RNA, including both the 1.7-kb HDV RNA and the 0.8-kb
      HDAg mRNA, from the genomic-sense RNA was surprisingly resistant to inhibition by
      L-HDAg. The synthesis of these RNAs was inhibited only when L-HDAg was in vast
      excess over S-HDAg. These results explain why HDV genomic RNA can initiate
      replication after infection even though the incoming viral genome is complexed
      with equal amounts of L-HDAg and S-HDAg. These results also suggest that the
      mechanisms of synthesis of genomic versus antigenomic RNA are different. This
      study thus resolves a puzzling question about the early events of the HDV life
      cycle.

PMID- 10906191
TI  - Evolution of circulating wild poliovirus and of vaccine-derived poliovirus in an
      immunodeficient patient: a unifying model.
AB  - We determined nucleotide sequences of the VP1 and 2AB genes and portions of the
      2C and 3D genes of two evolving poliovirus lineages: circulating wild viruses of
      T geotype and Sabin vaccine-derived isolates from an immunodeficient patient.
      Different regions of the viral RNA were found to evolve nonsynchronously, and the
      rate of evolution of the 2AB region in the vaccine-derived population was not
      constant throughout its history. Synonymous replacements occurred not completely
      randomly, suggesting the need for conservation of certain rare codons (possibly
      to control translation elongation) and the existence of unidentified constraints
      in the viral RNA structure. Nevertheless the major contribution to the evolution
      of the two lineages came from linear accumulation of synonymous substitutions.
      Therefore, in agreement with current theories of viral evolution, we suggest that
      the majority of the mutations in both lineages were fixed as a result of
      successive sampling, from the heterogeneous populations, of random portions
      containing predominantly neutral and possibly adverse mutations. As a result of
      such a mode of evolution, the virus fitness may be maintained at a more or less
      constant level or may decrease unless more-fit variants are stochastically
      generated. The proposed unifying model of natural poliovirus evolution has
      important implications for the epidemiology of poliomyelitis.

PMID- 10906192
TI  - Upregulation of tyrosine kinase TKT by the Epstein-Barr virus transactivator Zta.
AB  - The Zta protein is a key transactivator involved in initiating the Epstein-Barr
      virus (EBV) lytic cascade. In addition to transactivating many viral genes, Zta
      has the capacity to influence host cellular signals by binding to promoter
      regions or by interacting with several important cellular factors. Based on the
      observation that tyrosine kinases play central roles in determining the fate of
      cells, a kinase display assay was used to investigate whether cells expressing
      Zta have an altered pattern of kinase expression. The assay revealed that TRK
      related tyrosine kinase (TKT) is expressed at significant levels in Zta
      transfectants but not in control cells. Additional evidence was obtained from
      Northern and Western blotting. Importantly, the upregulation of phosphorylated
      TKT and TKT downstream effector matrix metalloproteinase 1 in Zta transfectants
      hinted that TKT might initiate a signaling cascade in Zta-expressing cells. In
      addition, deletion analysis of the Zta protein revealed that the transactivation
      and dimerization domains were both essential for the upregulation of TKT
      transcription. Moreover, correlation of expression levels of Zta and TKT
      transcripts in nasopharyngeal carcinoma biopsy specimens was clearly demonstrated
      by quantitative PCR (Q-PCR), which provides the first evidence for an effect of
      Zta on cellular gene expression in vivo. These findings offer insight into the
      virus-cell interactions and may help us elucidate the role of EBV in
      tumorigenesis.

PMID- 10906193
TI  - Definition of five new simian immunodeficiency virus cytotoxic T-lymphocyte
      epitopes and their restricting major histocompatibility complex class I
      molecules: evidence for an influence on disease progression.
AB  - Simian immunodeficiency virus (SIV) infection of the rhesus macaque is currently
      the best animal model for AIDS vaccine development. One limitation of this model,
      however, has been the small number of cytotoxic T-lymphocyte (CTL) epitopes and
      restricting major histocompatibility complex (MHC) class I molecules available
      for investigating virus-specific CTL responses. To identify new MHC class I
      restricted CTL epitopes, we infected five members of a family of MHC-defined
      rhesus macaques intravenously with SIV. Five new CTL epitopes bound by four
      different MHC class I molecules were defined. These included two Env epitopes
      bound by Mamu-A*11 and -B*03 and three Nef epitopes bound by Mamu-B*03, -B*04,
      and -B*17. All four restricting MHC class I molecules were encoded on only two
      haplotypes (b or c). Interestingly, resistance to disease progression within this
      family appeared to be associated with the inheritance of one or both of these MHC
      class I haplotypes. Two individuals that inherited haplotypes b and c separately
      survived for 299 and 511 days, respectively, while another individual that
      inherited both haplotypes survived for 889 days. In contrast, two MHC class I
      identical individuals that did not inherit either haplotype rapidly progressed to
      disease (survived <80 days). Since all five offspring were identical at their
      Mamu-DRB loci, MHC class II differences are unlikely to account for their
      patterns of disease progression. These results double the number of SIV CTL
      epitopes defined in rhesus macaques and provide evidence that allelic differences
      at the MHC class I loci may influence rates of disease progression among AIDS
      virus-infected individuals.

PMID- 10906194
TI  - Construction and characterization of murine cytomegaloviruses that contain
      transposon insertions at open reading frames m09 and M83.
AB  - A transposon derived from Escherichia coli Tn3 was introduced into the genome of
      murine cytomegalovirus (MCMV) to generate a pool of viral mutants, including two
      recombinant viruses that contained the transposon sequence within open reading
      frames m09 and M83. Our studies provide the first direct evidence to suggest that
      m09 is not essential for viral replication in mouse NIH 3T3 cells. Studies in
      cultured cells and in both BALB/c-Byj and CB17 severe combined immunodeficient
      (SCID) mice indicated that the transposon insertion is stable during viral
      propagation both in vitro and in vivo. Moreover, the virus that contained the
      insertion mutation in m09 exhibited a titer similar to that of the wild-type
      virus in the salivary glands, lungs, livers, spleens, and kidneys of both the
      BALB/c and SCID mice and was as virulent as the wild-type virus in killing the
      SCID mice when these animals were intraperitoneally infected with these viruses.
      These results suggest that m09 is dispensable for viral growth in these organs
      and that the presence of the transposon sequence in the viral genome does not
      significantly affect viral replication in vivo. In contrast, the virus that
      contained the insertion mutation in M83 exhibited a titer of at least 60-fold
      lower than that of the wild-type virus in the organs of the SCID mice and was
      attenuated in killing the SCID mice. These results demonstrate the utility of
      using the Tn3-based system as a mutagenesis approach for studying the function of
      MCMV genes in both immunocompetent and immunodeficient animals.

PMID- 10906195
TI  - Use of a transient assay for studying the genetic determinants of Fv1
      restriction.
AB  - To probe the genetic determinants controlling the interaction between the
      retroviral restriction gene Fv1 and its murine leukemia virus target, we set out
      to develop rapid, transient assays for Fv1 function. Cells were transfected or
      transduced with Fv1 expression plasmids which can produce green fluorescent
      protein via an internal ribosome entry site positioned between the Fv1 and green
      fluorescent protein coding sequences. Fv1 function was then assessed by comparing
      virus replication in green fluorescent protein-positive and -negative cells,
      using retroviral vectors encoding a second fluorescent marker, yellow fluorescent
      protein, or beta-galactosidase. Using this assay, we could show that Fv1
      specificities were not as absolute as previously thought, since the Fv1(b) allele
      was capable of interacting with "nonrestricted" B- and NB-tropic viruses and by
      shuffling the n- and b-alleles of Fv1, it was possible to generate a Fv1 molecule
      capable of restricting N-, B-, and NB-tropic viruses equally efficiently.
      Further, we could show that the presence of nonrestricting Fv1 in the same cell
      as restrictive Fv1 abrogates restriction, implying competition for binding to the
      retroviral target.

PMID- 10906196
TI  - Assembly of retrovirus capsid-nucleocapsid proteins in the presence of membranes
      or RNA.
AB  - Retrovirus Gag precursor (PrGag) proteins direct the assembly of roughly
      spherical immature virus particles, while after proteolytic processing events,
      the Gag capsid (CA) and nucleocapsid (NC) domains condense on viral RNAs to form
      mature retrovirus core structures. To investigate the process of retroviral
      morphogenesis, we examined the properties of histidine-tagged (His-tagged)
      Moloney murine leukemia (M-MuLV) capsid plus nucleocapsid (CANC) (His-MoCANC)
      proteins in vitro. The His-MoCANC proteins bound RNA, possessed nucleic acid
      annealing activities, and assembled into strand, circle (or sphere), and tube
      forms in the presence of RNA. Image analysis of electron micrographs revealed
      that tubes were formed by cage-like lattices of CANC proteins surrounding at
      least two different types of protein-free cage holes. By virtue of a His tag
      association with nickel-chelating lipids, His-MoCANC proteins also assembled into
      planar sheets on lipid monolayers, mimicking the membrane-associated immature
      PrGag protein forms. Membrane-bound His-MoCANC proteins organized into two
      dimensional (2D) cage-like lattices that were closely related to the tube forms,
      and in the presence of both nickel-chelating lipids and RNAs, 2D lattice forms
      appeared similar to lattices assembled in the absence of RNA. Our observations
      are consistent with a M-MuLV morphogenesis model in which proteolytic processing
      of membrane-bound Gag proteins permits CA and NC domains to rearrange from an
      immature spherical structure to a condensed mature form while maintaining local
      protein-protein contacts.

PMID- 10906197
TI  - Prolonged dominance of clonally restricted CD4(+) T cells in macaques infected
      with simian immunodeficiency viruses.
AB  - The repertoire of functional CD4(+) T lymphocytes in human immunodeficiency virus
      type 1-infected individuals remains poorly understood. To explore this issue, we
      have examined the clonality of CD4(+) T cells in simian immunodeficiency virus
      (SIV)-infected macaques by assessing T-cell receptor complementarity-determining
      region 3 (CDR3) profiles and sequences. A dominance of CD4(+) T cells expressing
      particular CDR3 sequences was identified within certain Vbeta-expressing
      peripheral blood lymphocyte subpopulations in the infected monkeys. Studies were
      then done to explore whether these dominant CD4(+) T cells represented expanded
      antigen-specific cell subpopulations or residual cells remaining in the course of
      virus-induced CD4(+) T-cell depletion. Sequence analysis revealed that these
      selected CDR3-bearing CD4(+) T-cell clones emerged soon after infection and
      dominated the CD4(+) T-cell repertoire for up to 14 months. Moreover, inoculation
      of chronically infected macaques with autologous SIV-infected cell lines to
      transiently increase plasma viral loads in the monkeys resulted in the dominance
      of these selected CDR3-bearing CD4(+) T cells. Both the temporal association of
      the detection of these clonal cell populations with infection and the dominance
      of these cell populations following superinfection with SIV suggest that these
      cells may be SIV specific. Finally, the inoculation of staphylococcal enterotoxin
      B superantigen into SIV-infected macaques uncovered a polyclonal background
      underlying the few dominant CDR3-bearing CD4(+) T cells, demonstrating that
      expandable polyclonal CD4(+) T-cell subpopulations persist in these animals.
      These results support the notions that a chronic AIDS virus infection can induce
      clonal expansion, in addition to depletion of CD4(+) T cells, and that some of
      these clones may be SIV specific.

PMID- 10906198
TI  - The murine gammaherpesvirus 68 v-cyclin is a critical regulator of reactivation
      from latency.
AB  - Gamma-2 herpesviruses encode a homolog of mammalian D-type cyclins. The v-cyclin
      encoded by murine gammaherpesvirus 68 (gammaHV68) induces cell cycle progression
      and is an oncogene (L. F. van Dyk, J. L. Hess, J. D. Katz, M. Jacoby, S. H.
      Speck, and H. W. Virgin IV, J. Virol. 73:5110-5122, 1999). However, the role of
      the pro-proliferative v-cyclins in gamma-2 herpesvirus pathogenesis is not known.
      Here we report the generation and characterization of a gammaHV68 v-cyclin mutant
      (v-cyclin.LacZ) that is unable to express a functional v-cyclin protein. Notably,
      although the gammaHV68 v-cyclin is expressed from an early-late lytic transcript,
      v-cyclin. LacZ replicated normally in fibroblasts in vitro and during acute
      infection in the spleen, liver, and lungs in vivo. Moreover, v-cyclin.LacZ
      exhibited wild-type (wt) virulence in mice with severe combined immunodeficiency.
      In addition, in a model of gammaHV68-induced chronic disease in mice lacking the
      gamma interferon receptor (IFNgammaR(-/-)), v-cyclin.LacZ virus was similar to wt
      gammaHV68 in terms of the incidence of mortality and vasculitis. Further analysis
      revealed that the frequencies of splenocytes and peritoneal cells harboring the
      latent gammaHV68 genome in normal and B-cell-deficient mice infected with wt
      gammaHV68 or v-cyclin.LacZ were very similar. However, v-cyclin.LacZ was
      significantly compromised in its capacity to reactivate from latency. This
      phenotype was conclusively mapped to the v-cyclin gene by (i) generating a marker
      rescue virus (v-cyclin.MR) from the v-cyclin.LacZ mutant, which restored the
      frequency of cells in which virus reactivated from latency to the levels observed
      with wt gammaHV68; and (ii) generating a second v-cyclin mutant virus containing
      a translation stop codon within the v-cyclin gene (v-cyclin.stop), which was
      compromised in reactivation from latency. These studies demonstrate that despite
      expression as a lytic cycle gene, the pro-proliferative gammaHV68 v-cyclin is not
      required for gammaHV68 replication either in vitro or during acute infection in
      vivo but rather is a critical determinant of reactivation from latency.

PMID- 10906199
TI  - Transgenic or plant expression vector-mediated recombination of Plum Pox Virus.
AB  - Different mutants of an infectious full-length clone (p35PPV-NAT) of Plum pox
      virus (PPV) were constructed: three mutants with mutations of the assembly motifs
      RQ and DF in the coat protein gene (CP) and two CP chimeras with exchanges in the
      CP core region of Zucchini yellow mosaic virus and Potato virus Y. The assembly
      mutants were restricted to single infected cells, whereas the PPV chimeras were
      able to produce systemic infections in Nicotiana benthamiana plants. After
      passages in different transgenic N. benthamiana plants expressing the PPV CP gene
      with a complete (plant line 4.30.45.) or partially deleted 3'-nontranslated
      region (3'-NTR) (plant line 17.27. 4.), characterization of the viral progeny of
      all mutants revealed restoration of wild-type virus by recombination with the
      transgenic CP RNA only in the presence of the complete 3'-NTR (4.30.45.).
      Reconstitution of wild-type virus was also observed following cobombardment of
      different assembly-defective p35PPV-NAT together with a movement-defective plant
      expression vector of Potato virus X expressing the intact PPV-NAT CP gene
      transiently in nontransgenic N. benthamiana plants. Finally, a chimeric
      recombinant virus was detected after cobombardment of defective p35PPV-NAT with a
      plant expression vector-derived CP gene from the sour cherry isolate of PPV (PPV
      SoC). This chimeric virus has been established by a double recombination event
      between the CP-defective PPV mutant and the intact PPV-SoC CP gene. These results
      demonstrate that viral sequences can be tested for recombination events without
      the necessity for producing transgenic plants.

PMID- 10906200
TI  - Induction of necrotic-like cell death by tumor necrosis factor alpha and caspase
      inhibitors: novel mechanism for killing virus-infected cells.
AB  - Induction of apoptotic cell death generally requires the participation of
      cysteine proteases belonging to the caspase family. However, and similar to most
      cell types, mouse fibroblasts are normally resistant to tumor necrosis factor
      alpha (TNF-alpha)-induced apoptosis. Surprisingly, TNF-alpha treatment of
      vaccinia virus-infected mouse fibroblasts resulted in necrotic-like cell death,
      which was significantly reduced in cells infected with a vaccinia virus mutant
      lacking the caspase inhibitor B13R. Furthermore, TNF-alpha also induced necrotic
      like cell death of fibroblasts in the presence of peptidyl caspase inhibitors. In
      both cases, necrosis was accompanied by generation of superoxide species. Caspase
      inhibitors also sensitized fibroblasts to killing by double-stranded RNA and
      gamma interferon. In all cases, cell death was efficiently blocked by
      antioxidants or mitochondrial respiratory chain inhibitors. These results define
      a new mitochondrion-dependent mechanism which may be important in the killing of
      cells infected with viruses encoding caspase inhibitors.

PMID- 10906201
TI  - Evasion of host defenses by measles virus: wild-type measles virus infection
      interferes with induction of Alpha/Beta interferon production.
AB  - Measles is a highly contagious disease currently responsible for over one million
      childhood deaths, particularly in the developing world. Since alpha/beta
      interferons (IFNs) are pivotal players both in nonspecific antiviral immunity and
      in specific cellular responses, their induction or suppression by measles virus
      (MV) could influence the outcome of a viral infection. In this study we compare
      the IFN induction and sensitivity of laboratory-passaged attenuated MV strains
      Edmonston and Moraten with those of recent wild-type viruses isolated and
      passaged solely on human peripheral blood mononuclear cells (PBMC) or on the B958
      marmoset B-cell line. We report that two PBMC-grown wild-type measles isolates
      and two B958-grown strains of MV induce 10- to 80-fold-lower production of IFN by
      phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL) compared to
      Edmonston and Moraten strains of measles. Preinfection of PBL with these non-IFN
      inducing MV isolates prevents Edmonston-induced but not double-stranded-RNA
      induced IFN production. This suggests that the wild-type viruses can actively
      inhibit Edmonston-induced IFN synthesis and that this is not occurring by double
      stranded RNA. Furthermore, the wild-type MV is more sensitive than Edmonston MV
      to the effect of IFN. MV is thus able to suppress the synthesis of the earliest
      mediator of antiviral immunity, IFN-alpha/beta. This could have important
      implications in the virulence and spread of MV.

PMID- 10906202
TI  - Simian immunodeficiency virus (SIV) gag DNA-vaccinated rhesus monkeys develop
      secondary cytotoxic T-lymphocyte responses and control viral replication after
      pathogenic SIV infection.
AB  - The potential contribution of a plasmid DNA construct to vaccine-elicited
      protective immunity was explored in the simian immunodeficiency virus
      (SIV)/macaque model of AIDS. Making use of soluble major histocompatibility class
      I/peptide tetramers and peptide-specific killing assays to monitor CD8(+) T
      lymphocyte responses to a dominant SIV Gag epitope in genetically selected rhesus
      monkeys, a codon-optimized SIV gag DNA vaccine construct was shown to elicit a
      high-frequency SIV-specific cytotoxic T-lymphocyte (CTL) response. This CTL
      response was demonstrable in both peripheral blood and lymph node lymphocytes.
      Following an intravenous challenge with the highly pathogenic viral isolate SIVsm
      E660, these vaccinated monkeys developed a secondary CTL response that arose with
      more rapid kinetics and reached a higher frequency than did the postchallenge CTL
      response in control plasmid-vaccinated monkeys. While peak plasma SIV RNA levels
      were comparable in the experimentally and control-vaccinated monkeys during the
      period of primary infection, the gag plasmid DNA-vaccinated monkeys demonstrated
      better containment of viral replication by 50 days following SIV challenge. These
      findings indicate that a plasmid DNA vaccine can elicit SIV-specific CTL
      responses in rhesus monkeys, and this vaccine-elicited immunity can facilitate
      the generation of secondary CTL responses and control of viral replication
      following a pathogenic SIV challenge. These observations suggest that plasmid DNA
      may prove a useful component of a human immunodeficiency virus type 1 vaccine.

PMID- 10906203
TI  - Murine model of interstitial cytomegalovirus pneumonia in syngeneic bone marrow
      transplantation: persistence of protective pulmonary CD8-T-cell infiltrates after
      clearance of acute infection.
AB  - Interstitial pneumonia (IP) is a severe organ manifestation of cytomegalovirus
      (CMV) disease in the immunocompromised host, in particular in recipients of bone
      marrow transplantation (BMT). Diagnostic criteria for the definition of CMV-IP
      include clinical evidence of pneumonia together with CMV detected in
      bronchoalveolar lavage or lung biopsy. We have used the model of syngeneic BMT
      and simultaneous infection of BALB/c mice with murine CMV for studying the
      pathogenesis of CMV-IP by controlled longitudinal analysis. A disseminated
      cytopathic infection of the lungs with fatal outcome was observed only when
      reconstituting CD8 T cells were depleted. Neither CD8 nor CD4 T cells mediated an
      immunopathogenesis of acute CMV-IP. By contrast, after efficient
      hematolymphopoietic reconstitution, viral replication in the lungs was moderate
      and focal. The histopathological picture was dominated by preferential
      infiltration of CD8 T cells confining viral replication to inflammatory foci.
      Notably, after clearance of acute infection, CD62L(lo) and CD62L(hi) subsets of
      CD44(+) memory CD8 T cells were found to persist in lung tissue. One can thus
      operationally distinguish an early CMV-positive IP (phase 1) and a late CMV
      negative IP (phase 2). According to the definition, phase 2 histopathology would
      not be diagnosed as a CMV-IP and could instead be misinterpreted as a CMV-induced
      immunopathology. We document here that phase 1 as well as phase 2 pulmonary CD8 T
      cells are capable of exerting effector functions and are effectual in protecting
      against productive infection. We propose that antiviral "stand-by" memory
      effector T cells persist in the lungs to prevent virus recurrence from latency.

PMID- 10906204
TI  - Characterization of the vaccinia virus H3L envelope protein: topology and
      posttranslational membrane insertion via the C-terminal hydrophobic tail.
AB  - The vaccinia virus H3L open reading frame encodes a 324-amino-acid immunodominant
      membrane component of virus particles. Biochemical and microscopic studies
      demonstrated that the H3L protein was expressed late in infection, accumulated in
      the cytoplasmic viral factory regions, and associated primarily with amorphous
      material near immature virions and with intracellular virion membranes.
      Localization of the H3L protein on the surfaces of viral particles and anchorage
      via the hydrophobic tail were consistent with its extraction by NP-40 in the
      absence of reducing agents, its trypsin sensitivity, its reactivity with a
      membrane-impermeable biotinylation reagent, and its immunogold labeling with an
      antibody to a peptide comprising amino acids 247 to 259. The H3L protein,
      synthesized in a coupled in vitro transcription/translation system, was tightly
      anchored to membranes as determined by resistance to Na(2)CO(3) (pH 11)
      extraction and cytoplasmically oriented as shown by sensitivity to proteinase K
      digestion. Further studies demonstrated that membrane insertion of the H3L
      protein occurred posttranslationally and that the C-terminal hydrophobic domain
      was necessary and sufficient for this to occur. These data indicated that the H3L
      protein is a member of the C-terminal anchor family and supported a model in
      which it is synthesized on free ribosomes and inserts into the membranes of viral
      particles during their maturation.

PMID- 10906205
TI  - Effects of deletion or stringent repression of the H3L envelope gene on vaccinia
      virus replication.
AB  - The C-terminal membrane anchor protein encoded by the H3L open reading frame of
      vaccinia virus is located on the surfaces of intracellular mature virions. To
      investigate the role of the H3L protein, we constructed deletion (vH3Delta) and
      inducible (vH3i) null mutants. The H3L protein was not detected in lysates of
      cells infected with vH3Delta or vH3i in the absence of inducer. Under these
      conditions, plaques were small and round instead of large and comet shaped,
      indicative of decreased virus replication or cell-to-cell spread. The mutant
      phenotype was correlated with reduced yields of infectious intra- and
      extracellular virus in one-step growth experiments. The defect in vH3i
      replication could not be attributed to a role of the H3L protein in virus
      binding, internalization, or any event prior to late gene expression. Electron
      microscopic examination of cells infected with vH3Delta or vH3i in the absence of
      inducer revealed that virion assembly was impaired, resulting in a high ratio of
      immature to mature virus forms with an accumulation of crescent membranes
      adjacent to granular material and DNA crystalloids. The absence of the H3L
      protein did not impair the membrane localization of virion surface proteins
      encoded by the A27L, D8L, and L1R genes. The wrapping of virions and actin tail
      formation were not specifically blocked, but there was an apparent defect in low
      pH-mediated syncytium formation that could be attributed to decreased virus
      particle production. The phenotypes of the H3L deletion and repression mutants
      were identical to each other but differed from those produced by null mutations
      of genes encoding other vaccinia virus membrane components.

PMID- 10906206
TI  - Modification of the cytoplasmic domain of influenza virus hemagglutinin affects
      enlargement of the fusion pore.
AB  - The fusion activity of chimeras of influenza virus hemagglutinin (HA) (from
      A/fpv/Rostock/34; subtype H7) with the transmembrane domain (TM) and/or
      cytoplasmic tail (CT) either from the nonviral, nonfusogenic T-cell surface
      protein CD4 or from the fusogenic Sendai virus F-protein was studied. Wild-type
      or chimeric HA was expressed in CV-1 cells by the transient T7-RNA-polymerase
      vaccinia virus expression system. Subsequently, the fusion activity of the
      expression products was monitored with red blood cells or ghosts as target cells.
      To assess the different steps of fusion, target cells were labeled with the
      fluorescent membrane label octadecyl rhodamine B-chloride (R18) (membrane fusion)
      and with the cytoplasmic fluorophores calcein (molecular weight [MW], 623;
      formation of small aqueous fusion pore) and tetramethylrhodamine-dextran (MW,
      10,000; enlargement of fusion pore). All chimeric HA/F-proteins, as well as the
      chimera with the TM of CD4 and the CT of HA, were able to mediate the different
      steps of fusion very similarly to wild-type HA. Quite differently, chimeric
      proteins with the CT of CD4 were strongly impaired in mediating pore enlargement.
      However, membrane fusion and formation of small pores were similar to those of
      wild-type HA, indicating that the conformational change of the ectodomain and
      earlier fusion steps were not inhibited. Various properties of the CT which may
      affect pore enlargement are considered. We surmise that the hydrophobicity of the
      sequence adjacent to the transmembrane domain is important for pore dilation.

PMID- 10906207
TI  - High levels of viral replication during primary simian immunodeficiency virus
      SIVagm infection are rapidly and strongly controlled in African green monkeys.
AB  - In contrast to pathogenic human immunodeficiency virus and simian
      immunodeficiency virus (SIV) infections, chronic SIVagm infections in African
      green monkeys (AGMs) are characterized by persistently low peripheral and tissue
      viral loads that correlate with the lack of disease observed in these animals. We
      report here data on the dynamics of acute SIVagm infection in AGMs that exhibit
      remarkable similarities with viral replication patterns observed in peripheral
      blood during the first 2 weeks of pathogenic SIVmac infections. Plasma viremia
      was evident at day 3 postinfection (p.i.) in AGMs, and rapid viral replication
      led by days 7 to 10 to peak viremias characterized by high levels of antigenemia
      (1.2 to 5 ng of p27/ml of plasma), peripheral DNA viral load (10(4) to 10(5) DNA
      copies/10(6) peripheral blood mononuclear cells [PBMC]), and plasma RNA viral
      load (2 x 10(6) to 2 x 10(8) RNA copies/ml). The lymph node (LN) RNA and DNA
      viral load patterns were similar to those in blood, with peaks observed between
      day 7 and day 14. These values in LNs (ranging from 3 x 10(5) to 3 x 10(6) RNA
      copies/10(6) LN cell [LNC] and 10(3) to 10(4) DNA copies/10(6) LNC) were at no
      time point higher than those observed in the blood. Both in LNs and in blood,
      rapid and significant decreases were observed in all infected animals after this
      peak of viral replication. Within 3 to 4 weeks p. i., antigenemia was no longer
      detectable and peripheral viral loads decreased to values similar to those
      characteristic of the chronic phase of infection (10(2) to 10(3) DNA copies/10(6)
      PBMC and 2 x 10(3) to 2 x 10(5) RNA copies/ml of plasma). In LNs, viral loads
      declined to 5 x 10(1) to 10(3) DNA copies and 10(4) to 3 x 10(5) RNA copies per
      10(6) LNC at day 28 p.i. and continued to decrease until day 84 p.i. (<10 to 3 x
      10(4) RNA copies/10(6) LNC). Despite extensive viremia during primary infection,
      neither follicular hyperplasia nor CD8(+) cell infiltration into LN germinal
      centers was detected. Altogether, these results indicate that the nonpathogenic
      outcome of SIVagm infection in its natural host is associated with a rapidly
      induced control of viral replication in response to SIVagm infection, rather than
      with a poorly replicating virus or a constitutive host genetic resistance to
      virus replication.

PMID- 10906208
TI  - Measles virus-induced immunosuppression in vitro is independent of complex
      glycosylation of viral glycoproteins and of hemifusion.
AB  - Expression of the measles virus (MV) F/H complex on the surface of viral
      particles, infected cells, or cells transfected to express these proteins
      (presenter cells [PC]) is necessary and sufficient to induce proliferative arrest
      in both human and rodent lymphoid cells (responder cells [RC]). This inhibition
      was found to occur independent of apoptosis and soluble mediators excluded by a
      pore size filter of 200 nm released from either PC or RC. We now show that
      reactive oxygen intermediates which might be released by RC or PC also do not
      contribute to MV-induced immunosuppression in vitro. Using an inhibitor of Golgi
      resident mannosidases (deoxymannojirimycin), we found that complex glycosylation
      of the F and H proteins is not required for the induction of proliferative arrest
      of RC. As revealed by our previous studies, proteolytic cleavage of the MV F
      protein precursor into its F1 and F2 subunits, but not of F/H-mediated cellular
      fusion, was found to be required, since fusion-inhibitory peptides such as Z-D
      Phe-L-Phe-Gly (Z-fFG) did not interfere with the induction of proliferative
      inhibition. We now show that Z-fFG inhibits cellular fusion at the stage of
      hemifusion by preventing lipid mixing of the outer membrane layer. These results
      provide strong evidence for a receptor-mediated signal elicited by the MV F/H
      complex which can be uncoupled from its fusogenic activity is required for the
      induction of proliferative arrest of human lymphocytes.

PMID- 10906210
TI  - Using chimeric hypoviruses to fine-tune the interaction between a pathogenic
      fungus and its plant host.
AB  - Infectious cDNA clones of mild (CHV1-Euro7) and severe (CHV1-EP713) hypovirus
      strains responsible for virulence attenuation (hypovirulence) of the chestnut
      blight fungus Cryphonectria parasitica were used to construct viable chimeric
      viruses. Differences in virus-mediated alterations of fungal colony morphology,
      growth rate, and canker morphology were mapped to a region of open reading frame
      B extending from nucleotides 2,363 to 9, 904. By swapping domains within this
      region, it was possible to generate chimeric hypovirus-infected C. parasitica
      isolates that exhibited a spectrum of defined colony and canker morphologies.
      Several severe strain traits were observed to be dominant. It was also possible
      to uncouple the severe strain traits of small canker size and suppression of
      asexual sporulation. For example, fungal isolates infected with a chimera
      containing nucleotides 2363 through 5310 from CHV1-Euro7 in a CHV1-713 background
      formed small cankers that were similar in size to that caused by CHV1-EP713
      infected isolates but with the capacity for producing asexual spores at levels
      approaching that observed for fungal isolates infected with the mild strain.
      These results demonstrate that hypoviruses can be engineered to fine-tune the
      interaction between a pathogenic fungus and its plant host. The identification of
      specific hypovirus domains that differentially contribute to canker morphology
      and sporulation levels also provides considerable utility for continuing efforts
      to enhance biological control potential by balancing hypovirulence and ecological
      fitness.

PMID- 10906209
TI  - Antibodies to CD9, a tetraspan transmembrane protein, inhibit canine distemper
      virus-induced cell-cell fusion but not virus-cell fusion.
AB  - Canine distemper virus (CDV) causes a life-threatening disease in several
      carnivores including domestic dogs. Recently, we identified a molecule, CD9, a
      member of the tetraspan transmembrane protein family, which facilitates, and
      antibodies to which inhibit, the infection of tissue culture cells with CDV
      (strain Onderstepoort). Here we describe that an anti-CD9 monoclonal antibody
      (MAb K41) did not interfere with binding of CDV to cells and uptake of virus. In
      addition, in single-step growth experiments, MAb K41 did not induce differences
      in the levels of viral mRNA and proteins. However, the virus release of syncytium
      forming strains of CDV, the virus-induced cell-cell fusion in lytically infected
      cultures, and the cell-cell fusion of uninfected with persistently CDV-infected
      HeLa cells were strongly inhibited by MAb K41. These data indicate that anti-CD9
      antibodies selectively block virus-induced cell-cell fusion, whereas virus-cell
      fusion is not affected.

PMID- 10906211
TI  - Essential and dispensable virus-encoded replication elements revealed by efforts
      To develop hypoviruses as gene expression vectors.
AB  - We have investigated whether hypoviruses, viral agents responsible for virulence
      attenuation (hypovirulence) of the chestnut blight fungus Cryphonectria
      parasitica, could serve as gene expression vectors. The infectious cDNA clone of
      the prototypic hypovirus CHV1-EP713 was modified to generate 20 different vector
      candidates. Although transient expression was achieved for a subset of vectors
      that contained the green fluorescent protein gene from Aequorea victoria, long
      term expression (past day 8) was not observed for any vector construct. Analysis
      of viral RNAs recovered from transfected fungal colonies revealed that the
      foreign genes were readily deleted from the replicating virus, although small
      portions of foreign sequences were retained by some vectors after months of
      replication. However, the results of vector viability and progeny
      characterization provided unexpected new insights into essential and dispensable
      elements of hypovirus replication. The N-terminal portion (codons 1 to 24) of the
      5'-proximal open reading frame (ORF), ORF A, was found to be required for virus
      replication, while the remaining 598 codons of this ORF were completely
      dispensable. Substantial alterations were tolerated in the pentanucleotide UAAUG
      that contains the ORF A termination codon and the overlapping putative initiation
      codon of the second of the two hypovirus ORFs, ORF B. Replication competence was
      maintained following either a frameshift mutation that caused a two-codon
      extension of ORF A or a modification that produced a single-ORF genomic
      organization. These results are discussed in terms of determinants of hypovirus
      replication, the potential utility of hypoviruses as gene expression vectors, and
      possible mechanisms by which hypoviruses recognize and delete foreign sequences.

PMID- 10906212
TI  - The structure of cucumber mosaic virus and comparison to cowpea chlorotic mottle
      virus.
AB  - The structure of cucumber mosaic virus (CMV; strain Fny) has been determined to a
      3.2-A resolution using X-ray crystallography. Despite the fact that CMV has only
      19% capsid protein sequence identity (34% similarity) to cowpea chlorotic mottle
      virus (CCMV), the core structures of these two members of the Bromoviridae family
      are highly homologous. As suggested by a previous low-resolution structural
      study, the 305-A diameter (maximum) of CMV is approximately 12 A larger than that
      of CCMV. In CCMV, the structures of the A, B, and C subunits are nearly identical
      except in their N termini. In contrast, the structures of two loops in subunit A
      of CMV differ from those in B and C. These loops are 6 and 7 residues longer than
      the analogous regions in CCMV. Unlike that of CCMV, the capsid of CMV does not
      undergo swelling at pH 7.0 and is stable at pH 9.0. This may be partly due to the
      fact that the N termini of the B and C subunits form a unique bundle of six
      amphipathic helices oriented down into the virion core at the threefold axes. In
      addition, while CCMV has a cluster of aspartic acid residues at the quasi
      threefold axis that are proposed to bind metal in a pH-dependent manner, this
      cluster is replaced by complementing acids and bases in CMV. Finally, this
      structure clearly demonstrates that the residues important for aphid transmission
      lie at the outermost portion of the betaH-betaI loop and yields details of the
      portions of the virus that are hypothesized to mediate binding to aphid
      mouthparts.

PMID- 10906213
TI  - Nondeletional T-cell receptor transgenic mice: model for the CD4(+) T-cell
      repertoire in chronic hepatitis B virus infection.
AB  - Chronicity after infection with the hepatitis B virus (HBV) can occur for a
      variety of reasons. However, once established, chronicity may be maintained by
      high levels of viral proteins circulating in the serum. To examine the
      characteristics of T cells capable of coexisting with the secreted hepatitis B e
      antigen (HBeAg), T-cell receptor (TCR) transgenic (Tg) mice were produced. To
      ensure that HBeAg-specific T cells would not be deleted in the presence of serum
      HBeAg, the TCR alpha- and beta-chain genes used to produce the TCR-Tg mice were
      derived from T-cell hybridomas produced from immunizing HBeAg-Tg mice. A TCR-Tg
      lineage (11/4-12) was produced that possessed a high frequency ( approximately
      67%) of CD4(+) T cells that expressed a Tg TCR specific for the HBeAg. As
      predicted, when 11/4-12 TCR-Tg mice were bred with HBeAg-Tg mice no deletion of
      the HBeAg-specific CD4(+) T cells occurred in the thymus or the spleen.
      Functional analysis of the TCR-Tg T cells revealed that the HBeAg-specific CD4(+)
      T cells escaped deletion in the thymus and periphery by virtue of low avidity.
      Regardless of their low avidity, HBeAg-specific TCR-Tg T cells could be activated
      by exogenous HBeAg, as measured by cytokine production in vitro and T-helper-cell
      function for anti-HBe antibody production in vitro and in vivo. Furthermore,
      activated TCR-Tg HBeAg-specific T cells polarized to the Th1 subset were able to
      elicit liver injury when transferred into HBeAg or HBcAg-Tg recipients.
      Therefore, HBeAg-specific CD4(+) T cells that can survive deletion or anergy in
      the presence of circulating HBeAg nonetheless are capable of being activated and
      of mediating liver injury in vivo. The 11/4-12 TCR-Tg lineage may serve as a
      monoclonal model for the HBe/HBcAg-specific CD4(+) T-cell repertoire present in
      chronically infected HBV patients.

PMID- 10906214
TI  - Identification of an export control sequence and a requirement for the KH domains
      in ICP27 from herpes simplex virus type 1.
AB  - The herpes simplex virus type 1 (HSV-1) immediate-early protein ICP27 is an RNA
      binding protein that performs multiple functions required for the expression of
      HSV-1 genes during a productive infection. One essential function involves
      shuttling between the nucleus and the cytoplasm. Some of the domains identified
      in ICP27 include a leucine-rich nuclear export sequence (NES), a nuclear
      localization signal, three KH-like RNA-binding domains, and an RGG-box type RNA
      binding motif. To study the contribution of two of the essential domains in ICP27
      to HSV gene expression, we generated recombinant herpesviruses carrying
      deleterious mutations in the NES and KH domains of ICP27. To accomplish this, we
      fused the green fluorescent protein (GFP) to ICP27 and utilized fluorescence as a
      marker to isolate recombinant herpesviruses. Fusion of GFP to wild-type ICP27 did
      not disturb its localization or function or significantly reduce virus yield.
      Analysis of HSV gene expression in cells infected with a recombinant virus
      carrying a point mutation in the first KH-like RNA-binding domain revealed that
      nuclear export of ICP27 was not blocked, and the expression of only a subset of
      ICP27-dependent late genes was affected. These findings suggest that individual
      KH-like RNA-binding motifs in ICP27 may be involved in binding distinct RNAs.
      Analysis of recombinant viruses carrying a lethal mutation in the NES of ICP27
      was not accomplished because this mutation results in a strong dominant-negative
      phenotype. Finally, we demonstrate that shuttling by ICP27 is regulated by an
      export control sequence adjacent to its NES that functions like the inhibitory
      sequence element found adjacent to the NES of NS1 from influenza virus.

PMID- 10906215
TI  - Hairy leukoplakia: an unusual combination of transforming and permissive Epstein
      Barr virus infections.
AB  - Human herpesviruses are characterized by distinct states of infection. Typically
      in permissive herpesvirus infection, abundant virus production results in cell
      lysis. In latent transforming Epstein-Barr virus (EBV) infection, viral proteins
      that induce cell growth are expressed. The immunodeficiency-associated hairy
      leukoplakia (HLP) lesion is the only pathologic manifestation of permissive EBV
      infection; however, within HLP, viral proteins characteristic of latent infection
      have also been detected. In this study, we further analyzed expression of EBV
      latent genes and investigated their contribution to the unique histologic
      phenotype of HLP. Coexpression of lytic and transforming viral proteins was
      detected simultaneously within individual HLP keratinocytes. LMP1 has now been
      shown to be uniformly expressed in the affected tissue, and it is associated and
      colocalizes with tumor necrosis factor receptor-associated factor (TRAF)
      signaling molecules. Effects induced by activated TRAF signaling that were
      detected in HLP included activation of NF-kappaB and c-Jun terminal kinase 1
      (JNK1) and upregulated expression of epidermal growth factor receptor (EGFR),
      CD40, A20, and TRAFs. This study identifies a novel state of EBV infection with
      concurrent expression of replicative and transforming proteins. It is probable
      that both replicative and latent proteins contribute to HLP development and
      induce many of the histologic features of HLP, such as acanthosis and
      hyperproliferation. In contrast to other permissive herpesvirus infections,
      expression of EBV transforming proteins within the permissively infected HLP
      tissue enables epithelial cell survival and may enhance viral replication.

PMID- 10906217
TI  - Efficient lytic infection of human arterial endothelial cells by human
      cytomegalovirus strains.
AB  - Endothelial cells (EC) are common targets of permissive infection by human
      cytomegalovirus (HCMV) in vivo during acute disease. However, studies of HCMV-EC
      interactions in vitro have generated discordant results. While lytic infection of
      cultured venous EC has been well established, Fish et al. (K. N. Fish, C.
      Soderberg Naucler, L. K. Mills, S. Stenglein, and J. A. Nelson, J. Virol. 72:5661
      5668) have reported noncytopathic persistence of the virus in cultured aortic EC.
      We propose that interstrain differences in viral host cell tropism rather than
      the vascular bed of origin of infected EC might account for these discrepancies.
      In the present investigation we compared the responses of EC derived from human
      adult iliac artery, placental microvasculature, and umbilical vein to infection
      with various HCMV strains. Regardless of the vascular bed of origin, infection
      with EC-propagated HCMV strains induced 100% efficient cytopathic change
      progressing to complete lysis of inoculated monolayers. While fibroblast
      propagated strains persisted at low titer in infected arterial EC cultures, they
      were also cytolytic for individual infected cells. The finding of cytopathic
      lytic infection of arterial EC by HCMV implicates a mechanism of vascular injury
      in the pathogenesis of HCMV infection.

PMID- 10906216
TI  - Infectious hematopoietic necrosis virus matrix protein inhibits host-directed
      gene expression and induces morphological changes of apoptosis in cell cultures.
AB  - Infectious hematopoietic necrosis virus (IHNV) infection in tissue culture cells
      has previously been shown to result in the shutdown of host protein synthesis,
      cell rounding, and cell death. We report here an investigation of the
      cytopathogenicity of the viral phosphoprotein (P or M1), matrix (M or M2), and
      nonvirion (NV) proteins in cultured fish cells. The expression of M alone
      potently inhibited reporter gene expression from a viral and an interferon (IFN)
      inducible promoter, whereas P and NV did not produce a similar effect. Northern
      blot analysis further revealed a reduction in the steady-state level of reporter
      mRNA when the M gene was cotransfected into cells; conversely, M mRNA was not
      drastically reduced in the same cells. By immunofluorescence confocal microscopy,
      fragmented nuclei were found in some cells expressing M protein but not in cells
      expressing P, NV, or beta-galactosidase protein. Electron microscopy revealed the
      morphological changes associated with apoptosis in the M-transfected cells.
      Furthermore, IHNV infection was shown to produce DNA "laddering" in cultured
      cells. Taken together, these data suggested at least two functions for M protein
      in an IHNV infection: down regulation of host transcription and the induction of
      programmed cell death. In the course of these experiments, we also discovered
      that NV expression was associated with cell rounding, the first biological effect
      on cells to be attributed to the NV gene.

PMID- 10906218
TI  - Structural and kinetic analyses of the protease from an amprenavir-resistant
      human immunodeficiency virus type 1 mutant rendered resistant to saquinavir and
      resensitized to amprenavir.
AB  - Recent drug regimens have had much success in the treatment of human
      immunodeficiency virus (HIV)-infected individuals; however, the incidence of
      resistance to such drugs has become a problem that is likely to increase in
      importance with long-term therapy of this chronic illness. An analysis and
      understanding of the molecular interactions between the drug(s) and the mutated
      viral target(s) is crucial for further progress in the field of AIDS therapy. The
      protease inhibitor amprenavir (APV) generates a signature set of HIV type 1 (HIV
      1) protease mutations associated with in vitro resistance (M46I/L, I47V, and I50V
      [triple mutant]). Passage of the triple-mutant APV-resistant HIV-1 strain in MT4
      cells, in the presence of increasing concentrations of saquinavir (SQV), gave
      rise to a new variant containing M46I, G48V, I50V, and I84L mutations in the
      protease and a resulting phenotype that was resistant to SQV and, unexpectedly,
      resensitized to APV. This phenotype was consistent with a subsequent kinetic
      analysis of the mutant protease, together with X-ray crystallographic analysis
      and computational modeling which elucidated the structural basis of these
      observations. The switch in protease inhibitor sensitivities resulted from (i)
      the I50V mutation, which reduced the area of contact with APV and SQV; (ii) the
      compensating I84L mutation, which improved hydrophobic packing with APV; and
      (iii) the G-to-V mutation at residue 48, which introduced steric repulsion with
      the P3 group of SQV. This analysis establishes the fine detail necessary for
      understanding the loss of protease binding for SQV in the quadruple mutant and
      gain in binding for APV, demonstrating the powerful combination of virology,
      molecular biology, enzymology, and protein structural and modeling studies in the
      elucidation and understanding of viral drug resistance.

PMID- 10906219
TI  - Apical gene transfer into quiescent human and canine polarized intestinal
      epithelial cells by lentivirus vectors.
AB  - Intestinal epithelial cells secrete a protective luminal mucus barrier inhibiting
      viral gene transfer. Quiescent, polarized monolayers of primary epithelial cells
      from dog gallbladder and human colon are efficiently transduced through the
      apical mucus side by lentivirus vectors, suggesting their application to
      intestinal gene therapy.

PMID- 10906220
TI  - Determination of the frequency of retroviral recombination between two identical
      sequences within a provirus.
AB  - Retroviruses use RNA as their genetic material within viral particles and DNA
      (provirus) as their genetic material within cells. The rate of recombination
      during reverse transcription between two identical sequences within the same RNA
      molecule is very high. In this study, we have developed a sensitive system to
      study recombination occurring within the proviral sequence. This system includes
      a murine Moloney leukemia virus vector which contains a neomycin resistance gene
      (neo) and two mutated green fluorescent protein genes (gfp) in tandem positions.
      The 3' end of the first gfp and the 5' end of the second gfp gene are both
      mutated, so that neither of these two gfp genes is functional. However, if
      recombination occurs between the two gfp genes it will create a functional gfp
      protein. Cells containing such a functional recombinant gfp appear green under
      fluorescence microscopy. The rate of recombination between the two gfp sequences
      during a single round of replication is as high as 51%. Green cells appear during
      proliferation of a clonal clear-cell population and allow a small portion of
      these recombinations between sequences of proviral DNA to be detected. The
      frequency of recombination at the proviral DNA level is about 10(-5) events/cell
      division, which is very low compared with the frequency of recombination (51%)
      caused by reverse transcriptase and/or RNA polymerase II.

PMID- 10906221
TI  - Attenuated modified vaccinia virus Ankara can be used as an immunizing agent
      under conditions of preexisting immunity to the vector.
AB  - A problem associated with the use of vaccinia virus recombinants as vaccines is
      the existence of a large human population with preexisting immunity to the
      vector. Here we showed that after a booster with attenuated recombinant modified
      vaccinia virus Ankara (rMVA), higher humoral and cellular immune responses to
      foreign antigens (human immunodeficiency virus type 1 Env and beta-galactosidase)
      were found in mice preimmunized with rMVA than in mice primed with the virulent
      Western Reserve strain and boosted with rMVA. This enhancement correlated with
      higher levels of expression of foreign antigens after the booster.

PMID- 10906223
TI  - Extensive homologous recombination among widely divergent TT viruses.
AB  - Analyses of a collection of full-length TT virus genomes showed nearly half of
      them to be recombinant. The results were highly significant and revealed
      homologous recombination both within and among genotypes, often involving
      extremely divergent lineages. Recombination breakpoints were significantly more
      common in the noncoding region of the TT virus genome than in the coding region.

PMID- 10906222
TI  - Complete DNA sequence of the rat cytomegalovirus genome.
AB  - We have determined the complete genome sequence of the Maastricht strain of rat
      cytomegalovirus (RCMV). The RCMV genome has a length of 229,896 bp and is
      arranged as a single unique sequence flanked by 504-bp terminal direct repeats.
      RCMV was found to have counterparts of all but one of the open reading frames
      (ORFs) that are conserved between murine CMV (MCMV) and human CMV (HCMV). Like
      HCMV, RCMV lacks homologs of the genes belonging to the MCMV m02 glycoprotein
      gene family. However, RCMV contains 15 ORFs with homology to members of the MCMV
      m145 glycoprotein gene family. Four ORFs are predicted to encode homologs of host
      proteins; R33 and R78 both putatively encode G protein-coupled receptors, whereas
      r144 and r131 encode homologs of major histocompatibility class I heavy chains
      and CC chemokines, respectively. An intriguing feature of the RCMV genome is the
      presence of an ORF, r127, with similarity to the rep gene of parvoviruses as well
      as ORF U94 of human herpesvirus 6A (HHV-6A) and HHV-6B. Counterparts of these
      ORFs have not been found in the other sequenced herpesviruses.

PMID- 10906224
TI  - Characteristics of the adeno-associated virus preintegration site in human
      chromosome 19: open chromatin conformation and transcription-competent
      environment.
AB  - Adeno-associated virus (AAV) establishes latency in infected cells by integrating
      into the cellular genome, with a high preference for a unique region, called
      AAVS1, of the human chromosome 19. The AAV proteins Rep78 and -68 are postulated
      to initiate the site-specific integration process by binding to a Rep binding
      site (RBS) in AAVS1. We provide further evidence to corroborate this model by
      demonstrating that the AAVS1 RBS in human cell lines is located near a DNase I
      hypersensitive "open" chromatin region and therefore is potentially easily
      accessible to Rep proteins. This open conformation is maintained in transgenic
      rats which carry an AAVS1 3. 5-kb DNA fragment and are proficient for Rep
      mediated site-specific integration. Interestingly, the core of the DNAse I
      hypersensitive site in AAVS1 corresponds to a sequence displaying transcriptional
      enhancer-like properties, suggesting that AAVS1 constitutes a transcription
      competent environment. The implications of our findings for AAV physiology and
      gene therapy are discussed.

PMID- 10906225
TI  - Immune response to recombinant adenovirus in humans: capsid components from viral
      input are targets for vector-specific cytotoxic T lymphocytes.
AB  - We previously demonstrated that a single injection of 10(9) PFU of recombinant
      adenovirus into patients induces strong vector-specific immune responses (H.
      Gahery-Segard, V. Molinier-Frenkel, C. Le Boulaire, P. Saulnier, P. Opolon, R.
      Lengagne, E. Gautier, A. Le Cesne, L. Zitvogel, A. Venet, C. Schatz, M. Courtney,
      T. Le Chevalier, T. Tursz, J.-G. Guillet, and F. Farace, J. Clin. Investig.
      100:2218-2226, 1997). In the present study we analyzed the mechanism of vector
      recognition by cytotoxic T lymphocytes (CTL). CD8(+) CTL lines were derived from
      two patients and maintained in long-term cultures. Target cell infections with E1
      deleted and E1-plus E2-deleted adenoviruses, as well as transcription-blocking
      experiments with actinomycin D, revealed that host T-cell recognition did not
      require viral gene transcription. Target cells treated with brefeldin A were not
      lysed, indicating that viral input protein-derived peptides are associated with
      HLA class I molecules. Using recombinant capsid component-loaded targets, we
      observed that the three major proteins could be recognized. These results raise
      the question of the use of multideleted adenoviruses for gene therapy in the
      quest to diminish antivector CTL responses.

PMID- 10906226
TI  - Coronavirus-induced demyelination occurs in the absence of inducible nitric oxide
      synthase.
AB  - Demyelination induced by mouse hepatitis virus (MHV), strain JHM, is in large
      part immune mediated, but little is known about the mechanisms involved in this
      process. Previous results suggest that inducible nitric oxide synthase (NOS2)
      contributes transiently to MHV-induced demyelination. Herein, we show that
      equivalent amounts of demyelination were evident at day 12 after MHV infection in
      mice genetically deficient in NOS2 (NOS2(-/-)) and in C57BL/6 mice. Furthermore,
      using an established adoptive transfer model and pharmacological inhibitors of
      NOS2 function, we could demonstrate no effect on MHV-induced demyelination. These
      results indicate that NOS2 function is not required for demyelination in mice
      infected with MHV.

PMID- 10906228
TI  - Initial interactions of subgenus D adenoviruses with A549 cellular receptors:
      sialic acid versus alpha(v) integrins.
AB  - Selected members of the adenovirus family have been shown to interact with the
      coxsackie adenovirus receptor, alpha(v) integrins, and sialic acid on target
      cells. Initial interactions of subgenus D adenoviruses with target cells have
      until now been poorly characterized. Here, we demonstrate that adenovirus type 8
      (Ad8), Ad19a, and Ad37 use sialic acid as a functional cellular receptor, whereas
      the Ad9 and Ad19 prototypes do not.

PMID- 10906230
TI  - Analysis of glycoconjugates

PMID- 10906227
TI  - Infection of nonhuman primate cells by pig endogenous retrovirus.
AB  - The ongoing shortage of human donor organs for transplantation has catalyzed new
      interest in the application of pig organs (xenotransplantation). One of the
      biggest concerns about the transplantation of porcine grafts into humans is the
      transmission of pig endogenous retroviruses (PERV) to the recipients or even to
      other members of the community. Although nonhuman primate models are excellently
      suited to mimic clinical xenotransplantation settings, their value for risk
      assessment of PERV transmission at xenotransplantation is questionable since all
      of the primate cell lines tested so far have been found to be nonpermissive for
      PERV infection. Here we demonstrate that human, gorilla, and Papio hamadryas
      primary skin fibroblasts and also baboon B-cell lines are permissive for PERV
      infection. This suggests that a reevaluation of the suitability of the baboon
      model for risk assessment in xenotransplantation is critical at this point.

PMID- 10906231
TI  - Electrophoretic methods for the analysis of N-linked oligosaccharides.

PMID- 10906232
TI  - Metabolic cytometry: monitoring oligosaccharide biosynthesis in single cells by
      capillary electrophoresis.

PMID- 10906229
TI  - Characterization of a novel respiratory syncytial virus-specific human cytotoxic
      T-lymphocyte epitope.
AB  - Respiratory syncytial virus (RSV) infection is a major cause of morbidity in
      childhood worldwide. The first human RSV-specific cytotoxic T-lymphocyte epitope
      to be defined is described. This HLA B7-restricted epitope in nucleoprotein (NP)
      was detectable in four healthy, B7-positive adult subjects using B7-RSV-NP
      tetrameric complexes to stain CD8(+) T cells.

PMID- 10906233
TI  - Electrophoresis for the analysis of acidic oligosaccharides.

PMID- 10906234
TI  - Measurement of oxidized glutathione by enzymatic recycling coupled to
      bioluminescent detection.
AB  - A new method is described for the quantification of oxidized glutathione (GSSG)
      in tissues by enzymatic recycling coupled to NADPH bioluminescent detection.
      Tissue samples are treated with metaphosphoric acid. In a first step, after
      derivatization of GSH with 4-chloro-7-trifluoromethyl-1-methylquinolinium (CFQ),
      GSSG is recycled in the presence of dithionitrobenzoic acid (DTNB) and NADPH by
      glutathione reductase. In a second step, the GSSG-dependent NADPH consumption is
      measured by luminescence with NADPH:FMN oxidoreductase-bacterial luciferase. The
      coefficient of variation for GSSG measurements on repeated assays (n = 5) is 2
      and 3% for standards and tissue samples, respectively. The sensitivity of this
      method is at the picomole level and is convenient for determination of GSSG
      physiological concentrations in tissues: GSSG levels measured in rat liver and
      kidney ranged from 76 to 215 and 52 to 170 nmol/g wet weight, respectively.

PMID- 10906235
TI  - Atomic force microscopy-based detection of binding and cleavage site of matrix
      metalloproteinase on individual type II collagen helices.
AB  - Type II tropocollagen molecules were reacted with matrix metalloproteinase 8 (MMP
      8) and the binding sites as well as the cleavage site of MMP-8 were detected on
      individual molecules using atomic force microscopy (AFM). Approximately 300-nm
      long coiled-coil tropocollagen molecules were straightened and immobilized on an
      atomically flat surface for detection by AFM. The direct visualization of
      individual collagen molecules revealed heterogeneous characteristics of MMP
      8:collagen complexes. We observed that there existed multiple MMP-8 nonspecific
      binding sites on the collagen molecules, but cleavage always took place at a
      unique site. When collagen molecules, straightened and immobilized on the
      surface, were reacted with MMP-8, a site of cleavage appeared as a gap in
      stretched molecules. This is the first report to visually show direct
      collagenase:collagen interactions using AFM. The described AFM-based analysis has
      potential as a protein analysis tool for understanding a complex mechanism of
      enzyme:substrate interactions.

PMID- 10906237
TI  - Calibrationless determination of creatinine and ammonia by coulometric flow
      titration.
AB  - A precise and sensitive working microflow titration procedure was developed to
      determine creatinine and ammonia in urine samples. This procedure is based on
      enzymatic conversion of creatinine, gas diffusional membrane separation of the
      released ammonia into an acid acceptor stream, and coulometric titration of
      ammonia with hypobromite. The hypobromite is formed after the electrogeneration
      of bromine in an electrolyte containing 1.0 M NaBr and 0.1 M sodium borate
      adjusted to pH 8.5. The electrolysis current follows a triangle-programmed
      current-time course. An amperometric flow detector records the resulting mirror
      symmetrical titration curves, which show two equivalence points. The analyte
      concentration is calculated from the time difference between the equivalence
      points. For quantitative conversion of creatinine and quantitative separation of
      present and released ammonia no calibration is necessary to get accurate results.
      Both ammonia/ammonium and creatinine were determined in the range between 2
      microM and 2 mM with relative standard deviations between 3.0 and 1.0% (n = 5).
      High recoveries were obtained for the analysis of diluted urine samples for both
      creatinine and ammonia.

PMID- 10906236
TI  - Native purification of biomolecules with temperature-mediated hydrophobic
      modulation liquid chromatography.
AB  - The high-resolution purification of native enzymes is impeded by the limitations
      in the mobile-phase choices required for conventional hydrophobic separations
      such as in reverse-phase chromatography. To avoid problems associated with
      varying the composition of the mobile phase, we developed a stationary phase with
      a hydrophobicity that can be modulated by slight variations in temperature to
      bind and elute biomolecules. This chromatographic matrix was tested on nucleotide
      analogs, amino acids, and protein samples. Visualization of the temperature
      dependent hydrophobic interaction with the chromatographic matrix was performed
      with fluorescence microscopy of CY3-ATP. Amino acids adsorbed to the column
      according to their known hydrophobicities, confirming the hydrophobic nature of
      their interaction with the matrix. Biomolecules were separated by modulating the
      hydrophobicity of the column matrix with slight adjustments to the running
      temperature between 22 and 37 degrees C without changing the mobile phase.
      Freedom in the choice of a mobile phase for both the loading and the elution of
      samples provides great practical advantages by eliminating the need for buffer
      exchange steps and allowing more native conditions for purifying delicate
      enzymes, such as myosin.

PMID- 10906238
TI  - Evaluation of silica resins for direct and efficient extraction of DNA from
      complex biological matrices in a miniaturized format.
AB  - For DNA purification to be functionally integrated into the microchip for high
      throughput DNA analysis, a miniaturized purification process must be developed
      that can be easily adapted to the microchip format. In this study, we evaluate
      the effectiveness of a variety of silica resins for miniaturized DNA purification
      and gauge the potential usefulness for on-chip solid-phase extraction. A micro
      solid-phase extraction (muSPE) device containing only nanograms of silica resin
      is shown to be effective for the adsorption and desorption of DNA in the picogram
      nanogram mass range. Fluorescence spectroscopy as well as capillary
      electrophoresis with laser-induced fluorescence detection is employed for the
      analysis of DNA recovered from solid-phase resins, while the polymerase chain
      reaction (PCR) is used to evaluate the amplifiable nature of the eluted DNA. We
      demonstrate that DNA can be directly recovered from white blood cells with an
      efficiency of roughly 70%, while greater than 80% of the protein is removed with
      a 500-nl bed volume muSPE process that takes less than 10 min. With a capacity in
      the range of 10-30 ng/mg of silica resin, we show that the DNA extracted from
      white blood cells, cultured cancer cells, and even whole blood on the low
      microliter scale is suitable for direct PCR amplification. The miniaturized
      format as well as rapid time frame for DNA extraction is compatible with the fast
      electrophoresis on microfabricated chips.

PMID- 10906239
TI  - Determination of carbohydrates, sugar alcohols, and glycols in cell cultures and
      fermentation broths using high-performance anion-exchange chromatography with
      pulsed amperometric detection.
AB  - Cell cultures and fermentation broths are complex mixtures of organic and
      inorganic compounds. Many of these compounds are synthesized or metabolized by
      microorganisms, and their concentrations can impact the yields of desired
      products. Carbohydrates serve as carbon sources for many microorganisms, while
      sugar alcohols (alditols), glycols (glycerol), and alcohols (methanol and
      ethanol) are metabolic products. We used high-performance anion-exchange
      chromatography with pulsed amperometric detection (HPAE-PAD) to simultaneously
      analyze for carbohydrates, alditols, and glycerol in growing yeast (Saccharomyces
      cerevisiae) cultures and their final fermentation broths. Both cultures were
      grown on complex undefined media, aliquots centrifuged to remove particulates,
      and the supernatants diluted and directly injected for analysis. Pulsed
      amperometry allowed a direct detection of the carbohydrates, alditols, and
      glycols present in the cultures and fermentation broths with very little
      interference from other matrix components. The broad linear range of three to
      four orders of magnitude allowed samples to be analyzed without multiple
      dilutions. Peak area RSDs were 2-7% for 2, 3-butanediol, ethanol, glycerol,
      erythritol, rhamnose, arabitol, sorbitol, galactitol, mannitol, arabinose,
      glucose, galactose, lactose, ribose, raffinose, and maltose spiked into a heat
      inactivated yeast culture broth supernatant that was analyzed repetitively for 48
      h. This method is useful for directly monitoring culture changes during
      fermentation. The carbohydrates in yeast cultures were monitored over 1 day. A
      yeast culture with medium consisting primarily of glucose and trace levels of
      trehalose and arabinose showed a drop in sugar concentration over time and an
      increase in glycerol. Yeast growing on a modified culture medium consisting of
      multiple carbohydrates and alditols showed preference for specific carbon sources
      and showed the ability to regulate pathways leading to catalysis of alternative
      carbon sources.

PMID- 10906240
TI  - A quantitative multistandard reverse transcriptase-polymerase chain reaction
      assay of the cystic fibrosis transmembrane conductance regulator: its usefulness
      in studying efficiency of gene transfer.
AB  - Procedures to quantify cystic fibrosis transmembrane conductance regulator (CFTR)
      mRNA levels have already been described but are not universally accepted, and
      many investigators are skeptical about quantification. To be able to accurately
      monitor gene therapy, we developed a quantitative multistandard RT-PCR method.
      This was based on the observation that the CFTR and ribosomal phosphoprotein PO
      (PR-PO) genes have retained important sequence homologies between rat and human
      species, allowing the use of rat RNA as an internal standard. A mixture of rat
      and human RNAs is simultaneously reverse-transcribed in one reaction tube and
      amplification of CFTR leads to rat and human amplificates with identical sizes
      which will be discriminated by restriction analysis. PR-PO is analyzed similarly
      and serves as a control of template loading. RT-PCR of different amounts of RNAs
      gave similar CFTR/PR-PO ratios, with a coefficient variation below 10%. This
      technique was applied to a cell line of cystic fibrosis tracheal gland serous
      cells (CF-KM4) incubated with a recombinant adenovirus containing the CFTR cDNA.
      Kinetics and dose dependency of transgene expression could be accurately
      quantified. This method is precise, reproducible, and very simple and could be
      applied to monitor gene therapy in minute amounts of tissue such as biopsies from
      cystic fibrosis patients.

PMID- 10906241
TI  - A new method for the determination of stability parameters of proteins from their
      heat-induced denaturation curves.
AB  - A new method has been developed for determining the stability parameters of
      proteins from their heat-induced transition curves followed by observation of
      changes in the far-UV circular dichroism (CD). This method of analysis of the
      thermal denaturation curve of a protein gave values of stability parameters that
      not only are identical to those measured by the differential scanning calorimetry
      (DSC), but also are measured with the same error as that observed with a
      calorimeter. This conclusion has been reached from our studies of the reversible
      heat-induced denaturation of lysozyme and ribonuclease A at various pH values.
      For each protein, the conventional method of analysis of the conformational
      transition curve, which assumes a linear temperature dependence of the pre- and
      posttransition baselines, gave the estimate of DeltaH(van)(m) (enthalpy change on
      denaturation at T(m), the midpoint of denaturation) which is significantly lower
      than DeltaH(cal)(m), the value obtained from DSC measurements. However, if the
      analysis of the same denaturation curve assumes that a parabolic function
      describes the temperature dependence of the pre- and posttransition baselines,
      there exists an excellent agreement between DeltaH(van)(m) and DeltaH(cal)(m) of
      the protein. The latter analysis is supported by the far-UV CD measurements of
      the oxidized ribonuclease A as a function of temperature, for the temperature
      dependence of this optical property of the protein is indeed nonlinear.
      Furthermore, it has been observed that, for each protein, the constant-pressure
      heat capacity change (DeltaC(p)) determined from the plots of DeltaH(van)(m)
      versus T(m) is independent of the method of analysis of the transition curve.

PMID- 10906242
TI  - Identification of proteins containing cysteine residues that are sensitive to
      oxidation by hydrogen peroxide at neutral pH.
AB  - A procedure for detecting proteins that contain H(2)O(2)-sensitive cysteine (or
      selenocysteine) residues was developed as a means with which to study protein
      oxidation by H(2)O(2) in cells. The procedure is based on the facts that H(2)O(2)
      and biotin-conjugated iodoacetamide (BIAM) selectively and competitively react
      with cysteine residues that exhibit a low pK(a), and that the decrease in the
      labeling of cell lysate proteins with BIAM caused by prior exposure of cells to
      H(2)O(2) or to an agent that induces H(2)O(2) production can be monitored by
      streptavidin blot analysis. This procedure was applied to rat pheochromocytoma
      PC12 cells directly treated with H(2)O(2), mouse hippocampal HT22 cells in which
      H(2)O(2) production was induced by glutamate, and human erythroleukemia K562
      cells in which H(2)O(2) production was induced by phorbol myristate acetate. It
      revealed that several cell proteins contain cysteine or selenocysteine residues
      that are selectively oxidized by H(2)O(2). Three of these H(2)O(2)-sensitive
      proteins were identified as a member of the protein disulfide isomerase family,
      thioredoxin reductase, and creatine kinase, all of which were previously known to
      contain at least one reactive cysteine or selenocysteine at their catalytic
      sites. This procedure should thus prove useful for the identification of proteins
      that are oxidized by H(2)O(2) generated in response to a variety of extracellular
      agents.

PMID- 10906243
TI  - Synthesis of [(32)P]phosphoramidate for use as a low molecular weight
      phosphodonor reagent.
AB  - Phosphoramidate serves as a useful phosphodonor reagent in protein and peptide
      phosphorylation, notably in studying two-component signal transduction systems in
      which low molecular weight phosphodonors can substitute for the phosphodonor
      function of histidine protein kinases in in vitro phosphorylation studies of
      response regulator proteins. A convenient method for the synthesis of
      radiolabeled phosphoramidate has not been developed, and this has limited its
      broader use. Here we report the synthesis of radiolabeled ammonium hydrogen
      phosphoramidate [(NH(4))H(32)PO(3)NH(2)] which is achieved by activation of
      [(32)P]orthophosphate with ethyl isocyanate followed by aminolysis with ammonium
      hydroxide to form the desired phosphoramidate. The procedure is conveniently
      carried out in a microfuge tube and requires only two successive precipitation
      steps to obtain pure ammonium hydrogen phosphoramidate. Molar yields of 15-30%
      and specific activities of 10-20 Ci/mol are readily achieved. Phosphorylation of
      microgram quantities of response regulator proteins CheY, CheB, and DrrA is
      shown. Low level, but detectable, nonspecific phosphorylation was observed for
      reactions near ambient temperatures when substrate response regulators lacking
      the active site aspartate but containing histidine residues are used. More
      significant levels of nonspecific phosphorylation were observed for reactions at
      elevated temperatures when using a nonresponse regulator control protein (RNase
      A).

PMID- 10906244
TI  - Quantitative determination of a chemically modified hammerhead ribozyme in blood
      plasma using 96-well solid-phase extraction coupled with high-performance liquid
      chromatography or capillary gel electrophoresis.
AB  - Versatile bioanalytical assays to detect chemically stabilized hammerhead
      ribozyme and putative ribozyme metabolites from plasma are described. The
      extraction protocols presented are based on serial solid-phase extractions
      performed on a 96-well plate format and are compatible with either IEX-HPLC or
      CGE back-end analysis. A validation of both assays confirmed that both the HPLC
      and the CGE methods possess the required linearity, accuracy, and precision to
      accurately measure concentrations of hammerhead ribozyme extracted from plasma.
      These methods should be of general use to detect and quantitate ribozymes from
      other biological fluids such as serum and urine.

PMID- 10906245
TI  - Affinity capture and recovery of DNA at femtomolar concentrations with peptide
      nucleic acid probes.
AB  - The efficacy of PNA vs DNA oligomers for the recovery of femtomolar
      concentrations of 16S rDNA targets was determined with solution- and mixed-phase
      hybridization formats and limiting dilution quantitative PCR. Several results
      contradict existing perceptions of expected PNA behavior deduced from
      hybridization studies with oligonucleotide targets at high concentration. For
      example, DNA probes in the solution hybridization format performed as well as or
      better than PNA probes under high- or low-salt conditions, regardless of
      hybridization time or target size. In the mixed-phase hybridization format,
      however, PNA probes showed certain advantages, with more rapid and efficient
      binding/recovery of target nucleic acids regardless of target size. Recovery of
      target DNA with PNA probes was always more efficient in low-salt (20 mM in Na(+))
      than high-salt (400 mM in Na(+-)) phosphate buffer. Recovery of target DNA by PNA
      probes was enhanced in the presence of excess, nontarget DNA, and differences in
      PNA efficacy under low- or high-salt conditions vanquished. In contrast, DNA
      probe performance was unaffected by the presence or absence of exogenous DNA in
      both solution- and mixed-phase hybridization formats. The absolute recovery and
      detection limit of the affinity purification method with either DNA or PNA probes
      was approximately 10(2) input target molecules at zeptamolar concentrations.

PMID- 10906246
TI  - Early indication of effects of puromycin aminonucleoside using a fluorimetric
      assay of 2-aminoacridone-derivatized carbohydrates in urine.
AB  - This paper describes a novel noninvasive method to study the changes in free
      carbohydrates excreted in urine as a result of toxicity in the rat induced by the
      administration of puromycin aminonucleoside (PAN). Urine samples were collected
      for 24 h prior to dosing and at 8, 24, and 32 h postdosing. For each sample, free
      carbohydrates were extracted from the urine using a graphitized carbon column and
      then labeled with 2-aminoacridone (2-AMAC) prior to analysis by hydrophilic
      interaction liquid chromatography (HILC). Dramatic changes were seen in the
      profile of the carbohydrates at the 8- and 24-h time points. These changes in
      carbohydrate profiles may be useful as early indicators of toxicity.

PMID- 10906247
TI  - Evaluation and comparison of ion permeation and agonist selectivities for N
      methyl-d-aspartate receptor channels with different subunit compositions in
      bilayer lipid membranes based on integrated single-channel currents.
AB  - To quantify the ion-permeation ability of the recombinant epsilon1-4/zeta1
      channel activated by agonists, the magnitude of agonist-induced integrated single
      channel currents for the epsilon2-4/zeta1 N-methyl-d-aspartate (NMDA) channels in
      bilayer lipid membranes (BLMs) was evaluated electrochemically based on the
      single-channel recordings. The recombinant epsilon2-4/zeta1 channels were
      purified from Chinese hamster ovary cells expressing each channel and
      incorporated in BLMs formed by the tip-dip method. Three typical agonists, l
      glutamate, NMDA, and (2S, 3R, 4S) isomer of 2-(carboxycyclopropyl)glycine (l-CCG
      IV), were investigated at a concentration of 50 microM. The magnitude of l
      glutamate-induced integrated current was found to depend on the epsilon-subunit
      composition and to increase in the order of epsilon2/zeta1 > epsilon1/zeta1
      approximately epsilon4/zeta1 > epsilon3/zeta1, which differs from that of the
      reported binding affinities (EC(50)) between l-glutamate and each channel type.
      On the other hand, the magnitude of the integrated currents induced by NMDA and l
      CCG-IV did not vary among the four channel types. The order of agonist
      selectivity toward the epsilon2-4/zeta1 channels in terms of the magnitude of the
      integrated current was l-glutamate > l-CCG-IV approximately NMDA for the
      epsilon2/zeta1 channel, l-CCG-IV > NMDA > l-glutamate for the epsilon3/zeta1
      channel, and l-CCG-IV approximately l-glutamate > NMDA for the epsilon4/zeta1
      channel, suggesting that the agonist selectivity also depends on the epsilon
      subunit composition. The present study shows that each epsilon1-4/zeta1 channel
      has its own ability of ion permeation, i.e., its own signal transduction ability,
      which is not parallel to its binding ability.

PMID- 10906248
TI  - Determination of blood folate using acid extraction and internally standardized
      gas chromatography-mass spectrometry detection.
AB  - Whole blood folate level is a superior indicator of folate nutritional status
      than serum/plasma level. Problems with and lack of confidence in results of
      current whole blood folate assays have limited its popularity for assessing
      folate nutritional status. Here, an acid extraction GCMS detection method that
      measures total folate whole blood is presented. Folates are released from the
      matrix of whole blood and cleaved to para-aminobenzoic acid (pABA) by acid
      hydrolysis in the presence of [(13)C(6)]pABA as internal standard (IS). The
      hydrolysate is passed over a C18 resin to remove heme. The pABA isotopomers are
      ethyl esterified, isolated on C18 resin, and trifluoroacetylated. Following
      normal-phase HPLC separation, the isotopomers are silylated to their tBDMS
      derivatives. The abundance of these derivatives are measured at m/z 324 for
      [(13)C(6)]pABA as IS and m/z 318 for pABA from whole blood folate. Our method
      uses readily available chemicals and our results agree well with those using
      Lactobacillus casei, the current gold standard reference assay. The presence of
      folate analogs (methotrexate) or antibacterials (sulfonamines) does not affect
      our method. This feature makes it useful in monitoring folate status of patients
      undergoing chemotherapy. Before using our method, pABA supplements must be
      discontinued for a few days.

PMID- 10906249
TI  - Effect of experimental zinc deficiency on immunological responses in Salmonella
      infected guinea-pigs.
AB  - Cellular and humoral immune responses to Salmonella dublin infection were studied
      in guinea-pigs given zinc-deficient (ZnD) or zinc-adequate (ZnA) diet, containing
      1.03 or 52.4 mg Zn/kg, respectively. On day 30, each animal of each dietary group
      was inoculated intraperitoneally with 10(6)viable cells of S. dublin strain 493.
      On the 15th day after infection, the immune responses were assessed by skin
      hypersensitivity (SH) tests and enzyme-linked immunosorbent assay (ELISA) for
      serum antibody with Salmonella -extract antigen. ZnD animals had significantly
      decreased ability to produce Salmonella -specific immediate and delayed type SH
      responses. These results were further substantiated by histological examination
      of skin sections. The ELISA indicated significantly lower Salmonella -specific
      serum antibody titres in ZnD animals than in ZnA animals. Mean viable counts of
      S. dublin in the liver and spleen of ZnD animals were significantly higher than
      those in ZnA animals.

PMID- 10906250
TI  - Hepatic granulomatous response to Schistosoma mansoni eggs in BALB/c mice and
      olive baboons (Papio cynocephalus anubis).
AB  - Hepatic granulomatous inflammation is one of the key pathological lesions of a
      patent Schistosoma mansoni infection. This study was concerned with the
      sequential induction, formation and eventual modulation of the schistosome egg
      granuloma in the mouse, which develops schistosome-induced hepatic fibrosis, and
      the olive baboon, which usually does not. Six baboons were each infected with
      1500 S. mansoni cercariae and liver biopsies were collected at weeks 6, 9, 13 and
      17 post-infection (p.i.). The mice (n=25) were each infected with 100 cercariae
      and killed in groups of five at weeks 6, 9, 12, 18 and 21 p.i. Peak granuloma
      size was observed at week 6 p.i. in baboons (mean 355 +/- 65.6 microm) but at
      week 12 p.i. in mice (299 +/- 40.5 microm). Eosinophils were more abundant in the
      baboon (60.6 +/- 8.9%) than in the mouse (41.2 +/- 8.4%) at the time of maximal
      granuloma size (P < 0.01). Neutrophils formed 21.1 +/- 6.3% of peak mouse
      granulomata but were virtually absent in baboon granulomata. A feature of the
      modulating baboon granulomata was the emergence of multinucleated giant cells
      (MGCs); modulating mouse granulomata, on the other hand, were characterized by
      infiltration of fibroblasts and collagen deposition. Thus, by week 21 p.i. mouse
      granulomata were 92 +/- 16.0 microm in diameter and well delineated by concentric
      layers of fibrous tissue. Granulomata, however, were present in only two of the
      baboons at week 17 p.i. (44 +/- 61.2 microm in diameter). The other four had peri
      portal cellular infiltration without granuloma formation, implying that baboon
      granulomata resolve spontaneously. These data suggest that high tissue
      eosinophilia and MGC formation are particularly efficient in bringing about the
      destruction of schistosome eggs and subsequent resolution of the egg granuloma
      without fibrosis. In conclusion, the baboon model more closely mimics the
      pathogenesis observed in man than does the mouse model.

PMID- 10906251
TI  - Oral infection of ferrets with virulent Mycobacterium bovis or Mycobacterium
      avium: susceptibility, pathogenesis and immune response.
AB  - Ferrets are important wildlife reservoirs of tuberculosis in New Zealand, where
      they acquire infection primarily through scavenging infected carrion. In the
      present study, groups of laboratory-reared ferrets were infected orally with 5 x
      10(6)colony-forming units of Mycobacterium bovis or Mycobacterium avium. Body
      weight and tuberculin-specific immune reactivity were monitored at intervals (pre
      infection, and 4 and 20 weeks post-infection) and animals were killed at 20 weeks
      post-infection for post-mortem, histopathological and bacteriological
      examinations. Weight loss was significantly greater in M. bovis -infected than in
      M. avium -infected ferrets. M. bovis, unlike M. avium, sometimes produced gross
      necrotic lesions in the mesenteric lymph nodes. M. bovis invariably produced
      microscopical foci of mycobacterial infection or tissue necrosis typical of
      tuberculosis, whereas M. avium did so in only one of nine animals. Mycobacteria
      were recovered from the lymphatic tissues of all M. bovis -infected ferrets but
      from only five of nine M. avium -infected animals; and the mean bacterial burdens
      of the lymph nodes of the head and intestinal regions were > 10-fold and > 100
      fold greater, respectively, for M. bovis -infected than for M. avium -infected
      animals. M. bovis, unlike M. avium, evoked tuberculin-specific peripheral blood
      lymphocyte reactivity and serum antibody responses.

PMID- 10906252
TI  - Effect of monensin sodium on histological lesions of naturally occurring bovine
      paratuberculosis.
AB  - Of 19 adult cows naturally infected with paratuberculosis, 13 were treated with
      monensin sodium and six remained untreated. At the beginning of the study, the
      severity of the histological lesions was assessed from biopsy samples of ileum,
      liver, mesenteric lymph node and rectal mucosa. From the data acquired it was
      possible to assign the animals so that the lesions in the two groups were similar
      (P=0. 8323). Monensin was administered in the feed, which contained 147.5 mg/kg,
      and each treated cow received 450 mg of monensin daily for 120 days. At the end
      of this period all cows were killed and histopathological findings in the ileum,
      liver, mesenteric lymph node and rectal mucosa were compared with the initial
      findings. A scoring system showed that monensin had a beneficial effect in the
      ileum (P=0.077), liver (P=0.0322) and rectal mucosa (P=0.0578), but under the
      conditions of the experiment no such effect could be demonstrated in mesenteric
      lymph node (P=0.3599). There appeared to be an overall effect on all tissues
      taken together (P=0.1335). The effect of monensin may have been due to both a
      halting and a reversal of the pathological process. In all but one of the six
      untreated cows, the lesions worsened during the course of the experiment.

PMID- 10906253
TI  - Reduction of pulmonary mast cells in areas of acute inflammation in calves with
      Mannheimia (Pasteurella) haemolytica pneumonia.
AB  - Mast cells in the left cranial pulmonary lobe of colostrum-deprived neonatal
      calves were quantified 2 and 6 h after intrabronchial inoculation with Mannheimia
      (Pasteurella) haemolytica A1. The mast cells were detected (1)
      immunohistochemically with a mouse anti-human mast cell tryptase monoclonal
      antibody, and (2) by metachromatic staining with low pH toluidine blue. A greater
      number of mast cells was demonstrated by the second method than by the first. At
      6 h after inoculation, but not at 2 h, the number of mast cells was significantly
      reduced at the site of the main lesions. Treatment of calves with a sialyl Lewis
      mimetic (TBC1269) did not appreciably affect the results at 6 h.

PMID- 10906254
TI  - Gross, histological and immunohistochemical features of mucormycosis in the
      platypus.
AB  - Nine male and five female adult free-living platypuses, obtained in a prospective
      capture-release study from northern Tasmania, exhibited gross features of
      cutaneous mycosis caused by Mucor amphibiorum. The lesions were present on the
      hind limbs (six cases), front limbs (four), tail (five), dorsal trunk (three) and
      ventral trunk (one). They varied in size, and ranged from raised red nodules or
      plaques, which sometimes exuded purulent material, to ulcerated lesions with
      central cavitation, red exuding centres and raised epidermal margins. Older
      lesions were covered either partly or fully by thickened and irregular epidermis.
      Histological examination of skin biopsies revealed discrete, poorly encapsulated
      granulomas, or more commonly a diffuse granulomatous or pyogranulomatous
      inflammation. Inflammatory cells consisted of neutrophils or eosinophils, sparse
      plasma cells and lymphocytes, many macrophages and occasional multinucleated
      giant cells. Fibrovascular tissue was diffusely and irregularly scattered in the
      granulomatous regions. Sphaerules characteristic of M. amphibiorum infection were
      observed in all lesions. The cutaneous distribution of the lesions and the
      natural history of the platypus indicated that entry of M. amphibiorum may have
      been via superficial skin wounds. T cells were the predominant infiltrating
      lymphoid cells in the diffuse lesions, indicating the importance of the cell
      mediated response to infection.

PMID- 10906255
TI  - Pathogenesis of classical swine fever: renal haemorrhages and erythrodiapedesis.
AB  - Thirty pigs were inoculated with a virulent isolate (Quillota strain) of
      classical swine fever (hog cholera) virus to establish the chronological
      occurrence of lesions in the kidney and to determine the mechanism responsible
      for renal haemorrhages. The study included the use of histopathological,
      ultrastructural, immunohistochemical (detection of viral antigen gp55, MAC387,
      lambda chains, CD3 and C1q) and morphometrical techniques (vascular area). Renal
      interstitial oedema and haemorrhages were detected from 7 days post-inoculation
      (dpi), associated with a slight interstitial mononuclear infiltrate and evidence
      of viral infection in macrophages and fibroblasts, and in a small proportion of
      lymphocytes. Viral infection was not detected in capillary endothelial cells. An
      intense mononuclear infiltrate, with B cells, T cells and small numbers of
      macrophages, was detected from 10 dpi. In the final phase of the experiment (14
      dpi), slight proliferation and degranulation of mast cells were observed.
      Increased expression of the C1q component of complement was also detected. A
      significant increase in vascular area was observed from 7 dpi. These results
      suggest that haemorrhages observed in the kidneys of pigs inoculated with the
      Quillota strain resulted from erythrodiapedesis and increased vascular
      permeability, probably aggravated by mast cell degranulation in the final stage
      of the experiment. The results suggested that mast cell degranulation was linked
      to activation of the complement system.

PMID- 10906256
TI  - Branchial cysts in laboratory mice.
AB  - Large solitary cysts in the superficial tissues of the ventral neck are described
      in five laboratory mice of two inbred strains and one outbred line. The cysts
      were lined by cuboidal to columnar epithelium similar to that in branchial cysts
      reported in other animal species but distinct from the stratified squamous
      epithelium with prominent lymphoid tissue typical of branchial cysts in man.
      These findings suggest that the lesion referred to as a branchial cyst in animals
      differs slightly from the lesion of the same name in man.

PMID- 10906257
TI  - Central nervous system metastasis of a cutaneous epitheliotropic lymphosarcoma in
      a dog.
AB  - This report describes an uncommon case of a cutaneous epitheliotropic T-cell
      lymphosarcoma with central nervous system (CNS) manifestations in a 9-year-old
      mixed breed German shepherd dog. The animal had a history of sudden blindness,
      pyrexia and multifocal areas of hyperaemia in the oral mucosa. A biopsy from the
      muco-cutaneous junction of the lips led to the diagnosis of an epitheliotropic
      lymphosarcoma and the animal was humanely destroyed. At necropsy, hyperaemia in
      the oral mucosa was no longer detectable. In the brain, a mass effacing the optic
      chiasm and invading the hypothalamic area was found; histological examination
      revealed lymphoid tumour cell infiltration. In the epithelium of the oral mucosa,
      intra-epithelial lymphoid tumour cells, sometimes arranged in small clusters
      (Pautrier's microabscesses), in combination with a mild inflammation in the
      superficial dermis were observed. Skin and brain tumour cells expressed CD3
      antigen, indicating their T-cell origin. This is, to our knowledge, the first
      report of a cutaneous epitheliotropic lymphosarcoma with CNS metastasis in a dog.

PMID- 10906258
TI  - Transmissible gastroenteritis virus induces apoptosis in swine testicular cell
      lines but not in intestinal enterocytes.
AB  - Evidence of apoptosis caused by infection with the Purdue strain of transmissible
      gastroenteritis virus (TGEV) was sought in vitro (in infected swine testicular
      [ST] cells) and in vivo (in the intestinal tissues of infected piglets). The
      methods used were (1) DNA electrophoresis for detection of DNA fragmentation, and
      (2) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      fluorescein nick and labelling (TUNEL). DNA "laddering" was detected in TGEV
      infected ST cells only. Numerous signs of apoptosis were detected in TGEV
      infected ST cells by TUNEL assay, the positive (dark brown) staining reaction
      being present in the majority of cell nuclei, without background staining. No
      such staining was seen in TGEV-infected enterocytes at various times after
      inoculation of piglets. Thus, it would appear that apoptosis does not occur in
      the enterocytes of piglets infected with TGEV.

PMID- 10906259
TI  - Hepatic ceroid-lipofuscinosis in enzootic cardiomyopathy of sika deer (Cervus
      nippon temminck).
AB  - Hepatic lesions in 25 sika deer (Cervus nippon Temminck) aged 1-15 days, affected
      by selenium-deficiency cardiomyopathy, were examined histopathologically.
      Characteristic pathological findings, induced by stagnation of the plasma
      proteins of the cytoplasm, consisted of vacuolar degeneration of hepatocytes,
      formation of hyalin droplets, and ceroid-lipofuscinosis. Electron
      microscopically, these changes were closely associated with degeneration of the
      endoplasmic reticulum and mitochondria. Peroxisomes, which were observed around
      the vacuoles, were regarded as a reactive result of membrane disturbance caused
      by a decrease in glutathione peroxidase (GSH-Px)

PMID- 10906260
TI  - Actinomycosis of dogs caused by Actinomyces hordeovulneris.
AB  - Actinomyces hordeovulneris was isolated from the lesions of chronic
      pyogranulomatous pleuritis and pericarditis of one of three dogs showing similar
      symptoms. The parietal pleura and the pericardium were thickened and covered with
      fine short threads of angiofibroblastic tissue. About 500-1000 ml of reddish
      purulent exudate in the thorax of all three dogs contained large numbers of rice
      grain-sized, soft, yellowish-white granules ("sulphur granules"). These granules
      had a central core of branching filaments of gram-positive bacteria embedded in
      thick granulation tissue. The parietal pleura, the mediastinal pleura and the
      pericardium were infiltrated mainly with neutrophils, and to a lesser extent with
      lymphocytes and plasma cells. A small number of eosinophils and giant cells was
      also observed. Large numbers of pyogranulomas embedded in the granulation tissue
      were composed of a core of necrotized granulation tissue, mixed with clusters of
      gram-positive branching bacteria, surrounded by an area of intact and
      degenerating neutrophils and lymphocytes. Bacteria were detected in the lesions
      by Brown-Brenn staining and were isolated from one of the affected animals. The
      isolated bacteria were identified as A. hordeovulneris. This was the first
      isolation of A. hordeovulneris in Hungary.

PMID- 10906261
TI  - Expression of two novel proteins in Chlamydia trachomatis during natural
      infection.
AB  - Genes for a putative membrane associated protein (mvi -homologue) and a 48 kDa
      protein (ctr48) in Chlamydia trachomatis were characterized. The mvi -homologue
      has 12 transmembrane domains and shows considerable homology to the members of
      this gene family in various organisms. The ctr48 has a leader sequence and the C
      proximal half is tryptophan-rich. The latter region shares 65% identity with the
      N-proxima third of C. pneumoniae 76 kDa protein over an overlap of 231 amino acid
      residues. The genes for the mvi -homologue and the ctr48 are present in the B,
      Ba, D, E, J and L2 serotypes of C. trachomatis. Immediately downstream from the
      ctr48 gene are multiple stop codons which are followed by a functional rho
      independent terminator. The mvi -homologue and ctr48 genes are independently
      transcribed, albeit poorly in serotype B. However, protein products corresponding
      to these genes could not be detected by western blotting in HEp2 cells infected
      with C. trachomatis. Nevertheless, antibodies to peptides corresponding to these
      proteins were detected in sera with high micro-immunofluorescence titre against
      C. trachoImatic, collected from a Chlamydia -endemic population. These results
      suggest that the mvi -homologue and ctr48 are expressed by C. trachomatis during
      natural infection.

PMID- 10906262
TI  - Isolation, sequencing and expression of Bartonella henselae omp43 and predicted
      membrane topology of the deduced protein.
AB  - The infection of and interaction of human endothelial cells with Bartonella
      henselae is one of the most interesting aspects of Bartonella -associated
      disease. The gene encoding the 43 kDa B. henselae outer membrane protein (Omp43)
      that binds endothelial cells was cloned and sequenced. Sequence analysis revealed
      an open reading frame of 1206 nucleotides coding for a protein of 402 amino
      acids. Analysis of the deduced amino acid sequence shows 38% identity over the
      entire sequence to the Brucella spp. In addition to this Omp2b porin also shows a
      signal sequence and peptidase cleavage site. Cleavage of the signal peptide
      results in a mature 380 amino acid polypeptide with a predicted molecular weight
      of 42 kDa. Omp43 was expressed in Escherichia coli as a fusion protein. Purified
      recombinant Omp43 at concentrations of 11 and 2.75 microg/ml bound to intact
      human umbilical vein endothelial cells. Membrane topology analysis predicts that
      Omp43 exists as a 16 stranded beta barrel protein, similar to that predicted for
      the Omp2b Brucella abortus porin. Characterization and expression of the gene
      encoding Omp43 should provide a tool for further investigation of the role of
      adherence to endothelial cells in the pathogenesis of B. henselae.

PMID- 10906263
TI  - Pneumococcal pneumonia and bacteremia model in mice for the analysis of
      protective antibodies.
AB  - Pneumococci cause infection by colonizing the nasopharynx and invading the
      mucosal surfaces. Infection models in mice, where the natural route of infection
      is mimicked, may be useful to study antibody mediated protection against
      pneumococcal pneumonia and bacteremia. We have established a pneumococcal
      pneumonia and bacteremia model in mice and investigated the protective capacity
      of human antibodies. Intranasal challenge with serotypes 1, 3, 6A and 8 caused
      lung infection and bacteremia which was lethal. Serotype 6B caused low, but
      detectable, infection and other serotypes tested were not virulent. Passive
      immunization with a human IgG preparation i.p. protected mice in a dose dependent
      manner against bacteremia caused by the virulent serotypes (except serotype 3)
      and partially or completely cleared pneumococci from the lungs of mice infected
      with serotypes 1, 6A and 8. Adsorption of antibodies with homologous capsular
      polysaccharides eliminated protection against disease but adsorption with cell
      wall polysaccharides (CWPS) did not. Furthermore, a good correlation was observed
      between protection of sera in vivo and opsonic activity in vitro. The results
      indicate that the model may be useful to analyse the levels, isotypes,
      specificity and other characteristics of human antibodies which protect against
      pneumococcal infection and to evaluate the protective potential of pneumococcal
      vaccine candidates.

PMID- 10906264
TI  - A pre-existing infection by Mycobacterium avium subsp. avium modulates anti
      Cryptococcus neoformans and anti-Candida albicans activities in human
      macrophages.
AB  - Mycobacterium avium is a facultative intracellular microorganism, able to survive
      and multiply within mammalian macrophages by circumventing antimicrobial
      mechanisms. In this study we hypothesize that pre-existing M. avium infection
      could result in macrophage superinfections by other microorganisms. We found that
      24 h after ingestion of M. avium at a low multiplicity of infection, macrophages
      are unable to efficiently produce superoxide anions when over-stimulated with
      phorbol esters, and that the generation of oxidative burst is only partially
      restored 72 h after bacteria ingestion. We also demonstrate that intracellular
      killing of Cryptococcus neoformans is markedly impaired in human macrophages that
      have previously ingested M. avium (but not other bacteria such as Escherichia
      coli). This inhibitory effect is observed with live mycobacteria, but not when
      heat-inactivated bacteria are ingested. In contrast, when Candida albicans is
      given to macrophages instead of C. neoformans, an enhancement of intracellular
      killing is observed, suggesting that cytocidal mechanisms other than respiratory
      burst are involved in the anti- Candidacidal activity of macrophages.

PMID- 10906265
TI  - Environmental conditions modulate the expression of the sspA and sspB genes in
      Streptococcus gordonii.
AB  - The SspA and SspB surface proteins of Streptococcus gordonii are multifunctional
      adhesins encoded by tandemly arranged genes. The transcriptional regulation of
      the sspA and sspB genes was investigated by generating chromosomal promoter- cat
      gene fusions and measuring CAT enzyme activity. The sspA promoter was found to be
      three-fold more active than the sspB promoter. In addition, sspA transcriptional
      activity increased throughout growth, whereas sspB activity decreased in
      stationary phase. Promoter activity of both sspA and sspB was regulated in
      response to temperature, pH and osmolarity; however the two promoters showed a
      different pattern of regulation. Changes in promoter activity were reflected in
      levels of surface protein and in adherence of S. gordonii to Porphyromonas
      gingivalis, a phenotypic property dependent on Ssp proteins. The results show
      that S. gordonii strain DL1 differentially regulates sspA and sspB transcription
      in response to oral environmental cues, suggesting that the SspA and SspB
      polypeptides may have distinct functional roles in cell adherence to oral
      substrates.

PMID- 10906266
TI  - Characterization of bacterial orofacial infections using a new murine model.
AB  - We devised a new murine orofacial infection model using bacteria from odontogenic
      infection origins and characterized the experimental infections. In this model,
      bacteria were injected into the submandible of mice. Streptococcus constellatus
      and Peptostreptococcus micros produced a single abscess at the injection site and
      their abscess-forming and lethal abilities were low: the median abscess-forming
      dose (AF(50)) of S. constellatus and P. micros were 10(8.5-10.7)and 10(10.2
      10.6)cfu/mouse, and their median lethal dose (LD(50)) were >11 and 10(10.6
      11)cfu/mouse, respectively. Prevotella oralis and Fusobacterium nucleatum
      produced multiple abscesses and their abscess-forming and lethal abilities were
      strong: AF(50)of P. oralis and F. nucleatum were 10(6.0-6.4)and 10(7. 0
      8.7)cfu/mouse, and their LD(50)were 10(7.0-7.7)and 10(8.3-9. 9)cfu/mouse,
      respectively. LD(50)of P. intermedia and P. gingivalis were 10(9.4->11)and 10(8.9
      9.1)cfu/mouse, respectively. Prevotella intermedia and Porphyromonas gingivalis
      generated a necrotizing lesion, which progressed rapidly. We conclude that this
      murine model could reflect human orofacial odontogenic infections and is useful
      to investigate the pathogenicity of causative bacteria of such infections.

PMID- 10906267
TI  - Experimental Salmonella typhi infection in the domestic pig, Sus scrofa
      domestica.
AB  - The domestic pig, Sus scrofa domestica, was examined as a model for typhoid
      fever, a severe and systemic disease of humans caused by Salmonella typhi. Six
      pigs were inoculated 1 week post-weaning with approximately 10(10)colony forming
      units (cfu) of wild type Salmonella typhi strain ISP1820 intranasally and
      observed for 3 weeks. S. typhi was cultured from the tonsils of 50% of the pigs
      at necropsy. Cultures from all other organs analysed (ileum, colon, spleen and
      liver) were negative. No clinical or histopathological signs of disease were
      observed. Pigs inoculated in parallel with swine-virulent S. choleraesuis all
      exhibited signs of systemic salmonellosis indicating that the parameters of the
      experimental infection with S. typhi (e.g. route) were appropriate. Whereas the
      pig has a gastrointestinal tract that is very similar to humans, our results
      indicated that the unique features of host and microbe interaction needed to
      produce typhoid fever were not mimicked in swine. Nevertheless, our observation
      of tonsillar involvement was consistent with former observations of S.
      choleraesuis and S. typhimurium infections in swine and supports a role for the
      tonsil in all porcine salmonella infections.

PMID- 10906269
TI  - Introduction.

PMID- 10906268
TI  - The cps locus of Streptococcus suis serotype 2: genetic determinant for the
      synthesis of sialic acid.
AB  - The capsule of S. suis serotype 2 is composed of glucose, galatose, N
      acetylglucosamine, rhamnose and sialic acid. Recently, we described a major part
      of the cps2 locus of S. suis serotype 2. Based on sequence homology genes
      encoding potential glucosyl-, galactosyl-, N-acetylglucosaminyl- and
      rhamnosyltransferase activities could be identified. However, we did not find
      genes involved in the synthesis of sialic acid. Here, we describe the cloning and
      characterization of a remaining part of the cps2 locus. Based on the establish
      sequence 11 potential genes, designated orf2L, orf2M, orf2N, cps2O to cps2T,
      orf2U and orf2V were identified. A gene homologous to genes involved in the
      polymerization of the repeating oligosaccharide unit (cps2O) as well as genes
      involved in the synthesis of sialic acid (cps2P to cps2T) were identified.
      Moreover, hybridizing experiments showed that the genes involved in the sialic
      acid synthesis are present in S. suis serotype 1, 2, 14, 27 and 1/2. The orf2M
      and orf2N regions showed similarity to proteins involved in the polysaccharide
      biosynthesis of other Gram-positive bacteria. However, these regions seemed to be
      truncated or were non-functional as the result of frame-shift or point mutations.
      At its 3;-end the cps2 locus contained two insertional elements (orf2U and
      orf2V), both of which seemed to be non-functional.

PMID- 10906271
TI  - Getting in and out of the proteasome.
AB  - By far the best understood role of the proteasome is to remove ubiquitin
      conjugated proteins from eukaryotric cells by hydrolysing them into small
      peptides of varying lengths. These include both misfolded/abnormal proteins, as
      well as 'normal' proteins that need to be rapidly removed for regulatory
      purposes. However, the proteasome is also present in numerous prokaryotic
      organisms, while ubiquitin, and the ubiquitin conjugating system, are not. The
      eukaryotic proteasome has been adapted to degrading proteins in a ubiquitin
      dependent fashion by the addition of regulatory factors that assemble in
      different layers onto the proteolytic core of the proteasome, and by increasing
      the diversity of the core subunits as well. In addition to hydrolysing
      ubiquitinated proteins into amino acids, the proteasome can also proteolyse
      selected non-ubiquitinated proteins, process proteins, and possibly refold
      misfolded proteins. This review will focus on the different proteasome functions,
      and how these are used in the multiple regulatory roles the proteasome plays in
      eukaryotic cells.

PMID- 10906270
TI  - Ubiquitination and deubiquitination: targeting of proteins for degradation by the
      proteasome.
AB  - The post-translational modification of proteins by covalent attachment of
      ubiquitin targets these proteins for degradation by the proteasome. An astounding
      number of proteins are involved in ubiquitination and deubiquitination of
      proteins. The pathways are combinatorial, and selectivity of proteolysis will
      depend strongly on the exact combination of ubiquitinating and deubiquitinating
      enzymes present at any time. In addition to temporal control, it is likely that
      these modifications are also regulated spatially. In this review, we discuss the
      regulation of ubiquitination by enzymes of this pathway and highlight some of the
      outstanding problems in understanding this regulation.

PMID- 10906272
TI  - Endoplasmic reticulum-associated protein degradation.
AB  - The quality control system in the endoplasmic reticulum of eukaryotic cells
      ensures that newly synthesized proteins that fail to fold into the correct
      conformation or unassembled orphan subunits of oligomeric proteins are rapidly
      eliminated by proteolytic degradation. This entails the export of proteins from
      the endoplasmic reticulum to the cytosol followed by their destruction by the
      cytosolic ubiquitin/proteasome pathway. While this mechanism effectively prevents
      the cellular accumulation of non-functional or unwanted endogenous proteins, it
      renders the cell vulnerable to certain viruses and toxins that are able to
      subvert this degradative mechanism for their own advantage.

PMID- 10906273
TI  - Targeting of lysosomal proteins.
AB  - Proper cell homeostasis requires the efficient transport of a large variety of
      soluble acid hydrolases and transmembrane proteins from the trans-Golgi network
      (TGN) to lysosomes. While most of these molecules reach this degradative
      compartment, some transmembrane proteins, in particular, the acid hydrolase
      receptors are retrieved to the TGN. This bidirectional transport process involves
      the formation of several vesicular transport intermediates in which cargo
      molecules are selectively packaged. This review summarizes our current
      understanding of the molecular mechanisms leading to the proper targeting of
      lysosomal proteins.

PMID- 10906274
TI  - Transport of proteins to the yeast vacuole: autophagy, cytoplasm-to-vacuole
      targeting, and role of the vacuole in degradation.
AB  - The vacuole/lysosome performs a central role in degradation. Proteins and
      organelles are transported to the vacuole by selective and non-selective
      pathways. Transport to the vacuole by autophagy is the primary mode for
      degradation of cytoplasmic constituents under starvation conditions. Autophagy
      overlaps mechanistically and genetically with a biosynthetic pathway termed Cvt
      (Cytoplasm-to-vacuole targeting) that operates under vegetative conditions to
      transport the resident vacuolar hydrolase aminopeptidase I (API). API import has
      been dissected to reveal the action of a novel mechanism that transports cargo
      within double-membrane vesicles. Recent work has uncovered molecular components
      involved in autophagy and the Cvt pathway.

PMID- 10906275
TI  - Protein degradation in mitochondria.
AB  - The biogenesis of mitochondria and the maintenance of mitochondrial functions
      depends on an autonomous proteolytic system in the organelle which is highly
      conserved throughout evolution. Components of this system include processing
      peptidases and ATP-dependent proteases, as well as molecular chaperone proteins
      and protein complexes with apparently regulatory functions. While processing
      peptidases mediate maturation of nuclear-encoded mitochondrial preproteins,
      quality control within various subcompartments of mitochondria is ensured by ATP
      dependent proteases which selectively remove non-assembled or misfolded
      polypeptides. Moreover; these proteases appear to control the activity- or steady
      state levels of specific regulatory proteins and thereby ensure mitochondrial
      genome integrity, gene expression and protein assembly.

PMID- 10906276
TI  - Proteolytic regulation of apoptosis.
AB  - Much of the proteolysis that occurs during apoptosis is directed by caspases, a
      family of related cysteinyl proteases. A relatively small number of cellular
      proteins are targeted by caspases, yet their function is dramatically affected
      and apoptosis is triggered. Other proteases, such as granzymes and calpain, are
      also involved in the apoptotic signaling process, but in a much more cell type-
      and/or stimulus type-specific manner. At least three distinct caspase-signaling
      pathways exist; one activated through ligand-dependent death receptor
      oligomerization, the second through mitochondrial disruption, and the third
      through stress-mediated events involving the endoplasmic reticulum. These
      pathways also appear to interact to amplify weak apoptotic signals and shorten
      cellular execution time. Finally, defects in caspases contribute to autoimmune
      disease, cancer and certain neurological disorders.

PMID- 10906277
TI  - Protein degradation in MHC class II antigen presentation: opportunities for
      immunomodulation.
AB  - Proteolysis is required for two steps of the MHC class II antigen-processing
      pathway, degradation of invariant chain and cleavage of protein antigens.
      Invariant chain dissociation from MHC is limited by a final proteolytic event
      which is tightly regulated in both temporal and tissue-specific ways. In
      contrast, enzymes involved in antigen proteolysis remain ill-defined. Gene
      'knockout' experiments of housekeeping proteolytic enzymes suggest either that
      these enzymes do not play a major role, or that antigen proteolysis is too
      degenerate for this type of analysis. The possible role of two other proteinases,
      cathepsin E and aspariginyl endopeptidase is discussed. Finally, the data
      implicating antigen processing in repertoire generation is briefly considered. We
      conclude that selective regulation of endosomal proteolysis could have profound
      implications for control of immunity against infection, as well as in
      autoimmunity.

PMID- 10906278
TI  - Proteolysis and developmental signal transduction.
AB  - Regulated proteolysis is a critical feature of many intercellular signalling
      pathways that control cell-fate specification and tissue patterning during
      metazoan development. The roles of proteolysis in three different pathways, the
      Toll, Hedgehog, and Notch pathways, are described to illustrate the importance of
      specific protein cleavages in both extracellular ligand-receptor interactions and
      intracellular signal transduction. An emerging principle is the use of
      proteolysis to control the maturation and activation of receptors, to limit the
      spatial diffusion of their ligands, and to modulate the subcellular localization
      or transcriptional activity of DNA-binding factors in response to receptor-ligand
      interactions at the cell surface.

PMID- 10906279
TI  - DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in fetal tissues of
      patas monkeys after transplacental exposure.
AB  - Transplacental genotoxicity of the heterocyclic amine food-derived
      mutagen/carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has been
      investigated by (32)P-postlabeling assay for IQ-DNA adducts in maternal liver,
      placenta, and several fetal tissues of patas monkeys, after exposure to 15, 35,
      or 50 mg/kg IQ near the end of gestation or to the highest dose in the first or
      second trimester. Dose-dependent adduct formation occurred in all tissues, with
      the highest levels occurring in maternal liver. Adduct amounts were similar among
      fetal tissues and placenta, except for lower levels in fetal brain and slightly
      more adducts in fetal liver. Adducts in placenta, fetal liver, lung, kidney,
      skin, and adrenal gland, but not in maternal liver or fetal brain, increased
      significantly as gestation progressed. Pretreatment with phenobarbital, which
      induces CYP enzymes that detoxify IQ, decreased adducts in maternal liver and
      possibly placenta, but not in fetal tissues. The CYP inducer beta-naphthoflavone
      caused a significant increase in IQ-DNA adducts in fetal lungs. Regression
      analysis suggested that IQ activation in maternal and fetal liver and possibly
      placenta contributed to adduct formation in fetal tissues; adducts in placenta
      and/or fetal liver were strong predictors for those in most fetal tissues. The
      results indicate that exposure of pregnant primates to IQ results in DNA adduct
      formation in most fetal tissues, especially late in gestation; that upregulation
      of maternal detoxification does not provide fetal protection; and that adducts in
      placenta indicate adduct levels in fetal tissues.

PMID- 10906280
TI  - Augmented humoral immune function in metallothionein-null mice.
AB  - Stress response proteins can play integral roles as modulators of cellular
      function and can be involved in mechanisms that are important to immune function.
      Metallothionein (MT), a cysteine-rich stress response protein, has been shown to
      play numerous roles in the cell: it serves as a reservoir of essential heavy
      metals, it scavenges free radicals, and it can sequester heavy metals. These
      various functions suggest that MT may also participate in modulating immune
      responses. In previous work, we have shown that exogenous metallothionein can
      suppress the developing humoral immune response when coinjected with antigen. The
      present study was designed to evaluate the effects of endogenous MT on the
      development of humoral immunity. We compared the humoral immune function of
      animals with a targeted disruption of Mt-1 and -2 genes (MTKO) and their wild
      type counterparts. MTKO mice displayed a significantly higher humoral response to
      challenge with ovalbumin (OVA) compared to wild-type controls. The secondary anti
      OVA response in MTKO mice is as much as 58% higher than the response in control
      mice injected at the same time. Overall circulatory immunoglobulin levels are
      also substantially higher in MTKO mice (0.039 mg/ml IgM and 0.42 mg/ml IgG) than
      wild-type controls. MTKO mice displayed increased B cell differentiation
      following OVA challenge and an enhanced lymphoproliferative response to mitogenic
      stimulation. These changes in immune functional capacity occur in the context of
      changes in the makeup of the lymphoid compartments of the blood and spleen. There
      are substantially fewer T and B cells in the circulation of MTKO mice, but more T
      cells in the spleen of these mice than in control animals. Finally, we have found
      that splenocytes from MTKO animals displayed significantly elevated levels of NF
      kappaB activity compared to wild-type controls. In conclusion, we have provided
      evidence that endogenous metallothionein can modulate the immune response in vivo
      and that intracellular MT may modulate immune function by regulation of
      transcription factor activity.

PMID- 10906281
TI  - Synergistic hepatotoxicity from coexposure to bacterial endotoxin and the
      pyrrolizidine alkaloid monocrotaline.
AB  - Individuals are commonly exposed to bacterial endotoxin (lipopolysaccharide
      [LPS]) through gram-negative bacterial infection and from its translocation from
      the gastrointestinal lumen into the circulation. Inasmuch as noninjurious doses
      of LPS augment the hepatotoxicity of certain xenobiotic agents, exposure to small
      amounts of LPS may be an important determinant of susceptibility to chemical
      intoxication. Monocrotaline (MCT) is a pyrrolizidine alkaloid phytotoxin that at
      large doses produces centrilobular liver lesions in rats. In the present study,
      MCT was coadministered with LPS to determine whether LPS would enhance its
      hepatotoxicity. Doses of MCT (100 mg/kg, ip) and LPS (7.4 x 10(6) EU/kg, iv),
      which were nonhepatotoxic when administered separately, produced significant
      liver injury in male, Sprague-Dawley rats when given in combination. Within 18 h
      after MCT administration, this cotreatment resulted in enhanced plasma alanine
      aminotransferase and aspartate aminotransferase activities, two markers of liver
      injury. Histologically, overt hemorrhage and necrosis appeared between 12 and 18
      h. The lesions were centrilobular and midzonal and exhibited characteristics
      similar to lesions associated with larger doses of MCT and LPS, respectively. In
      the presence of LPS, the threshold for MCT toxicity was reduced to 13-33% of the
      dose required for toxicity with MCT alone. A study in isolated, hepatic
      parenchymal cells revealed no interaction between MCT and LPS in producing
      cytotoxicity. In summary, coexposure of rats to noninjurious doses of MCT and LPS
      resulted in pronounced liver injury. Results in vitro suggest that the enhanced
      toxicity does not result from a direct interaction of MCT and LPS with hepatic
      parenchymal cells. These results provide additional evidence that exposure to
      small amounts of LPS may be a determinant of susceptibility to food-borne
      hepatotoxins.

PMID- 10906282
TI  - Vanadocene-mediated in vivo male germ cell apoptosis.
AB  - Vanadocenes are potent apoptosis-inducing cytotoxic agents against human
      testicular cancer cells in vitro. The present study investigated the ability of
      four vanadocenes-vanadocene diazide (VDA), vanadocene dicyanate (VDCN),
      vanadocene dioxycyanate (VDOCN), and vanadocene monochloro oxycyanate (VDCO)-to
      induce male germ cell apoptosis in vivo in mouse testes by repetitive
      intratesticular injection of vanadocenes (7.5 mg/kg/testis) for 28 days. Germ
      cell loss in vivo was measured by epididymal sperm count, testes weights, and
      histologic evaluation of the testes. Repetitive intratesticular injection of
      vanadocenes led to decreased sperm counts and reduced testicular weights.
      Histopathological examination revealed seminiferous tubular atrophy, inhibition
      of spermatogenesis, and the preferential loss of maturing and elongated
      spermatids. In situ evaluation by the terminal deoxynucleotidyl transferase
      mediated FITC-deoxyuridine triphosphate nick-end labeling (TUNEL) of seminiferous
      tubule cross sections and laser confocal microscopy showed characteristic
      apoptotic cells identified primarily as pachytene spermatocytes delineating the
      periphery of the seminiferous tubules. The ability of vanadocenes to induce germ
      cell apoptosis in vivo may have potential utility in the treatment of testicular
      seminomas in humans.

PMID- 10906283
TI  - Role of lipid peroxidation and poly(ADP-ribose) polymerase activation in oxidant
      induced membrane transport dysfunction in opossum kidney cells.
AB  - This study was undertaken to examine the role of lipid peroxidation and poly(ADP
      ribose) polymerase (PARP) activation in H(2)O(2)-induced inhibition of Na(+)
      dependent phosphate (Na(+)-Pi) uptake in opossum kidney (OK) cells. H(2)O(2)
      inhibited Na(+)-Pi uptake in a dose-dependent manner. H(2)O(2)-induced inhibition
      of Na(+)-Pi uptake was prevented by dithiothreitol and glutathione. A potent
      antioxidant, DPPD, had no effect on H(2)O(2) inhibition of Na(+)-Pi uptake,
      despite completely inhibiting lipid peroxidation induced by H(2)O(2). However, in
      primary cultured rabbit proximal tubular cells, the effect of H(2)O(2) on Na(+)
      Pi uptake was significantly prevented by DPPD, suggesting a species difference in
      the role of lipid peroxidation in the inhibition of Na(+)-Pi uptake occurring
      with H(2)O(2). t-Butylhydroperoxide (tBHP) caused the inhibition of Na(+)-Pi
      uptake that was prevented by DPPD in OK cells and rabbit proximal tubular cells.
      The PARP inhibitor 3-aminobenzamide completely protected the inhibition of Na(+)
      Pi uptake induced by H(2)O(2) but not by tBHP. H(2)O(2)-induced ATP depletion was
      prevented by 3-aminobenzamide but not by DPPD. tBHP-induced ATP depletion was
      prevented by DPPD, whereas it was not altered by 3-aminobenzamide. Effects of
      H(2)O(2) and tBHP on Na(+)-Pi uptake and ATP depletion were prevented by an iron
      chelator, deferoxamine, suggesting that the oxidants inhibit Na(+)-Pi uptake
      through an iron-dependent mechanism. The extent of DNA damage by tBHP was similar
      to that by H(2)O(2). These results indicate that the effect of H(2)O(2) on
      membrane transport function in OK cells is associated with PARP activation but
      not lipid peroxidation, whereas the effect of tBHP is associated with lipid
      peroxidation.

PMID- 10906284
TI  - Effects of microtubule-associated protein (MAP) expression on methylmercury
      induced microtubule disassembly.
AB  - The sensitivity of microtubules (MTs) to methylmercury- (MeHg) induced
      disassembly was compared in undifferentiated, MAP1A- and MAP2C-transfected, and
      neuronally differentiated P19 Embyronal Carcinoma (EC) cells. The extent of MT
      disassembly was examined qualitatively by immunofluorescence microscopy and
      Western blotting and quantitatively by dot blotting of polymer and soluble
      proteins extracts. Immunofluorescence microscopy showed that MeHg disassembled
      MTs in a time- and dose-dependent manner and that MTs in both MAP2C-transfected
      and neuronally differentiated cells, but not those in MAP1A-transfected cells,
      were significantly more resistant to MeHg-induced MT depolymerization than those
      in undifferentiated cells. These results suggest that MAP2C has a greater ability
      to stabilize MTs against MeHg-induced disassembly than MAP1A. Surprisingly,
      however, when the extent of MT disassembly was assessed by Western blotting and
      by quantitative dot blotting, no change was observed in the amounts of tubulin,
      MAP2, or MAP1A, in the polymer and soluble fractions in MeHg-treated samples,
      compared to the control cells that were not treated. These data show that,
      although MeHg treatment resulted in the disassembly of MTs, they were not
      depolymerized as detergent-soluble subunits, but rather appeared to form
      insoluble tubulin-MAP oligomers or aggregates.

PMID- 10906285
TI  - CTL hyporesponsiveness induced by 2,3,7, 8-tetrachlorodibenzo-p-dioxin: role of
      cytokines and apoptosis.
AB  - Studies have shown that blocking B7-mediated costimulation induces T cell
      tolerance via anergy or apoptosis. Provision of exogenous IL-2 can reverse or
      prevent the induction of tolerance. We have previously shown that TCDD-induced
      suppression of the CTL response to allogeneic P815 tumor cells is accompanied by
      decreased expression of CD86 (B7-2) as well as suppressed IL-2 and IFNgamma
      production. In the present studies, the role of IL-2 and IFNgamma and the
      analysis of inappropriate deletion of CD8(+) cells was examined. Administration
      of IL-2 on days 7-9 relative to the injection of P815 tumor cells dose
      dependently increased the CTL activity and the generation of CD8(+) CTL effector
      cells in TCDD-treated mice. This increased CTL response was not due to
      recruitment of naive CTL precursors (CTLp), suggesting that a small pool of
      activated CTLp in TCDD-treated mice could respond to the IL-2. A much larger pool
      of activated CTLp in control mice was also expanded by IL-2 treatment. In
      contrast, treatment with IFNgamma during the same time period did not alter CTL
      activity in control or TCDD-treated mice. To address the possibility that
      insufficient IL-2 early in the response was responsible for the reduced pool of
      activated CTLp in TCDD-treated mice, IL-2 was administered on days 1-3 after P815
      injection. However, not only did early treatment with IL-2 fail to restore the
      response in TCDD-treated mice, it suppressed the CTL response of non-TCDD-treated
      mice. To test whether exposure to TCDD induced apoptosis of activated CD8(+) T
      cells, phosphatidylserine (PS) expression was measured on various days after P815
      tumor challenge. Surprisingly, the percentage of apoptotic CD8(+) T cells was
      significantly lower in TCDD-treated mice compared to controls throughout the
      allograft response. Similarly, exposure to TCDD failed to enhance peripheral
      deletion of Vbeta3(+)CD8(+) T cells after injection of the superantigen
      Staphylococcal enterotoxin A (SEA). Taken together, the data indicate that TCDD
      induces an early defect in CTLp activation that is not due to insufficient IL-2
      or deletion of CD8(+) cells and may implicate a novel mechanism by which ligands
      of the Ah receptor disrupt CTL precursor activation.

PMID- 10906286
TI  - A single dose of Di-(2-ethylhexyl) phthalate in neonatal rats alters gonocytes,
      reduces sertoli cell proliferation, and decreases cyclin D2 expression.
AB  - In this study, we explored the impact on both Sertoli cells and gonocytes of a
      single, relatively low dose of di-(2-ethylhexyl) phthalate (DEHP; 20-500 mg/kg)
      administered in vivo to 3-day-old rat pups. In parallel, we assessed the
      potential for two immediate metabolites of DEHP to produce similar testicular
      changes and began to explore the possible mechanisms involved. Morphological
      examination revealed the presence of many abnormally large, multi-nucleated germ
      cells by 24 h posttreatment with DEHP and with its metabolite, mono-ethylhexyl
      phthalate (MEHP), but not with another metabolite, 2-ethylhexanol (2-EH; all at
      1.28 mmol/kg) or with vehicle alone. These cells persisted through 48 h
      posttreatment, the longest time point examined in our study. We also assessed the
      rate of Sertoli cell proliferation in pups at intervals after dosage with either
      chemical or vehicle by administering bromodeoxy uridine (BrdU) 3 h before
      euthanasia. By 24 h after treatment with DEHP or MEHP, but not 2-EH or vehicle,
      the number of BrdU-labeled Sertoli cells was obviously diminished in testicular
      sections. Quantitation of DEHP-treated pups and controls indicates that a dose
      response relationship exists between chemical treatment and labeling index (LI)
      of Sertoli cells, with a LI at the highest DEHP dose tested that was only 20% of
      that in controls. In addition, when we examined the time course of the effect of
      an intermediate dose of DEHP, we found that there the LI of Sertoli cells
      rebounds by 48 h after dosage, when we found the rate of proliferation in treated
      pups to be significantly higher than in controls. We also explored the potential
      mechanism involved in the response to DEHP and found serum levels of FSH to be
      unaffected by the chemical. In addition, study of cell cycle-related proteins
      including p27kip1 and cyclins D1, D2, and D3 with Western and Northern analysis
      indicated that cyclin D2 mRNA is specifically down-regulated by DEHP in a dose
      dependent manner, and this decrease is manifest as a small, transient but
      reproducible reduction in the amount of cyclin D2 protein detectable in samples
      from treated pups compared to controls. Our findings characterize the changes in
      neonatal Sertoli cells and gonocytes that follow in vivo to low levels of DEHP
      and its metabolite, MEHP, as well as providing new information on the underlying
      mechanism and highlighting the extreme sensitivity of the neonatal testis to
      injury by this toxicant.

PMID- 10906288
TI  - Chemical index for volume 166

PMID- 10906289
TI  - Cochrane collaborative review group on peripheral vascular Diseases:Review
      abstracts

PMID- 10906287
TI  - Succimer and the reduction of tissue lead in juvenile monkeys.
AB  - The extent to which succimer (2,3-dimercaptosuccinic acid, DMSA) chelation
      reduces target organ lead (Pb) levels, including the skeleton, relative to the
      cessation of Pb exposure is a primary consideration in evaluating its efficacy
      for reducing toxicity in children. Here, we utilized a rhesus monkey model of
      childhood Pb exposure and a sensitive stable (204)Pb isotope tracer methodology
      to determine the efficacy of succimer for reducing Pb in blood, liver, and
      skeletal tissues from chronic (>/=1 year) versus short-term (3-4 days) Pb
      exposures. Specific attention was paid to the efficacy of succimer treatment
      compared to the cessation of Pb exposure. Infant rhesus monkeys (n = 48) were
      exposed to Pb daily for 1 year or >1 year postpartum to reach and maintain a
      target blood Pb level of 35-40 microg/dL. Two successive 19-day succimer
      treatment regimens were administered at 53 and 65 weeks of age (30 mg/kg/day x 5
      days followed by 20 mg/kg/day x 14 days). Blood was collected over the course of
      treatment, and liver and bone biopsy samples were collected on days 0, 5, and 20,
      relative to the start of treatment (day 0). Complete 24-h urine collections were
      conducted over the course of treatment. Results of the first chelation indicate
      that a single regimen of succimer treatment led to significant reductions in
      blood and liver Pb levels, relative to the placebo group. However, the cessation
      of Pb exposure alone (i.e., placebo) also led to significant reductions in blood
      and liver compared to pretreatment levels. Neither succimer nor the cessation of
      Pb exposure had a significant impact on bone lead levels. Blood Pb levels in the
      succimer-treated group rebounded within 5 days after treatment ended, becoming
      comparable with levels in the placebo group from that point on. Results from the
      second chelation indicate that succimer treatment is essentially equally
      efficacious in reducing blood Pb at moderate (20 microg/dL) levels where
      exposures ended >3 months previously and more elevated (40-50 microg/dL) levels
      where exposures ended just prior to treatment, relative to the placebo treatment.
      Finally, similar overall outcomes were observed for tissue Pb from recent
      exposures (i.e., (204)Pb tracer levels), indicating little or no apparent
      difference in the chelation of Pb from recent (3-4 days) versus long-term
      exposures. These data demonstrate that succimer does not reduce skeletal Pb
      levels, and they show that the efficacy of succimer for reducing blood Pb levels
      does not persist beyond the completion of treatment due to posttreatment rebounds
      in blood Pb from endogenous sources. They also demonstrate the relative benefit
      of eliminating Pb exposures, which serves to underscore the importance of primary
      prevention of Pb exposure. The extent to which these data reflect the efficacy of
      succimer for reducing neurocognitive impairment is not yet known, although those
      data are forthcoming.

PMID- 10906290
TI  - Exercise therapy or angioplasty? A summation analysis.
AB  - OBJECTIVES: To compare the outcome of exercise therapy or angioplasty for the
      treatment of patients with intermittent claudication. DESIGN: A summation
      analysis. METHODS: A search using MEDLINE and PUBMED between 1966 and April 1999
      followed by a review of the manuscripts yielded 54 studies involving angioplasty
      and 27 studies involving exercise therapy for intermittent claudication. Studies
      were only included (12 angioplasty and nine exercise series) when results were
      available for patients with intermittent claudication alone, and when outcome was
      assessed in terms of symptoms at a minimum of 6 months. RESULTS: The total number
      of claudicants undergoing exercise therapy was 294 patients, with a mean
      symptomatic success rate of 38. 4% and a mean improvement in maximum walking
      distance of 189.7% at 6 months. The total number of claudicants undergoing
      angioplasty was 2071, with a mean overall symptomatic success rate of 76.6%. The
      mean overall complication rate was 9% and mean major complication rate was 2.7%
      for the angioplasty studies. CONCLUSION: Although the result demonstrates an
      advantage of angioplasty over exercise therapy at 6 months, there is a small risk
      of major complications. However, comparison of studies was impaired due to
      disparity in patient numbers, limited follow-up time and lack of uniformity in
      outcome assessment. In order to achieve a valid comparison of these therapies in
      a future randomised study, a validated disease-specific instrument for the
      assessment of symptomatic outcome for claudicants is required.

PMID- 10906291
TI  - Rapid thawing increases the fragility of the cryopreserved arterial wall.
AB  - OBJECTIVE: To extend present knowledge of the biomechanical and structural
      changes which occur in the cryopreserved, rapidly thawed arterial wall. MATERIALS
      AND METHODS: Minipig iliac arterial segments were cryopreserved at -196 degrees C
      in either minimum essential medium or Wisconsin solution. Fresh segments served
      as the control group. After 1 month, the specimens were rapidly thawed (37
      degrees C) and processed for biomechanical, ultrastructural, morphological and
      immunohistochemical (MMP-1, MMP-2, MMP-3 and MMP-9) analysis. Visualisation of
      apoptotic cells was performed by TUNEL method. For the mechanical distension
      analysis, an in vitro circuit was designed. RESULTS: The cryopreserved segments
      showed a 42% incidence of spontaneous fracture and the appearance of
      microfractures which affected the endoluminal third of the vessel. An
      accumulation of liquid in the subelastica was observed. An increased expression
      of wall-degradative enzymes (mainly MMP-2) was also observed following
      cryopreservation. No significant differences were detected in the proportional
      elasticity module or tensile strength of the specimen groups. No differences in
      mechanical distension were observed between groups after the vessel segments were
      subjected to the pulsatile circuit flow for 72 h. Cell damage was most intense in
      the specimens cryopreserved in Wisconsin solution. CONCLUSIONS: Cryopreservation
      in both the solutions employed, followed by rapid thawing, induce changes in the
      permeability which increase the fragility of the cryopreserved arterial wall.
      Both increased expression of wall-degradative enzymes and accumulation of liquid
      may contribute to graft failure after implantation.

PMID- 10906292
TI  - The mechanical properties of fresh and cryopreserved arterial homografts.
AB  - OBJECTIVES: To assess the effect of cryopreservation on the elasticity and
      compliance of arterial allografts. MATERIALS AND METHODS: Iliofemoral segments of
      arteries and veins harvested from multiorgan donors were divided into two groups:
      fresh-control, tested for 24 hours after harvesting, and cryopreserved in liquid
      nitrogen after pretreatment with 20% dimethylsulphoxide and stored for an average
      time of 22 days. Vessel wall elastic properties were evaluated from the stress
      strain relationship in a specially designed test cell fixed to the Instron
      Universal Testing Machine. RESULTS: The elastic modulus of the artery control
      group (1.54+/-0.33 MPa, n=20) was not significantly different from the
      cryopreserved group (1.69+/-0.61 MPa, n=15). Similarly, values for unfrozen veins
      (3.11+/-0.65 MPa, n=47) were not significantly different from those of frozen
      samples (2.71+/-0.85 MPa, n=38). Control compliance (6. 86+/-1.79x10(-5)%/Pa, for
      arteries; 3.84+/-0.81x10(-5)%/Pa, for veins) was similar to that of the
      cryopreserved group (6.66+/-1. 80x10(-5)%/Pa, for arteries; 4.16+/-1.21x10(
      5)%/Pa, for veins). CONCLUSIONS: Cryopreservation maintains the important elastic
      properties of arterial and venous allografts during average storage time of 22
      days.

PMID- 10906293
TI  - Variation of method for measurement of brachial artery pressure significantly
      affects ankle-brachial pressure index values.
AB  - BACKGROUND: Mmeasurement of ankle brachial pressure indices (ABPI) is important
      in the assessment of patients with peripheral vascular disease. METHODS: Thirty
      one hospitals with a vascular surgeon were selected at random. A telephone
      questionnaire was completed to assess the method used for the measurement of
      ABPI. Following the survey, 14 patients with peripheral vascular disease had
      their ABPI measurement done by two observers, a pre-registration house officer
      and a clinical nurse practitioner. Observers were blinded to their own and each
      other's results. Brachial systolic pressures were obtained using a
      DINAMAP(TM)(Critikon, Tampa, U.S.A.) automated blood pressure monitor, the
      Korotkoff method (12 cm cuff, parallel wrap) and an 8 MHz Doppler probe
      (Huntleigh) and sphygmomanometer. Ankle systolic pressures were obtained using
      the Doppler probe. The results were analysed using the Wilcoxon signed rank test.
      RESULTS: The survey demonstrated that at the majority of centres with vascular
      laboratories the brachial artery systolic pressures were measured using a Doppler
      probe. In contrast, at centres where the house officers performed the routine
      measurements, over 60% used the Korotkoff method to obtain this reading. One in
      four nurse practitioners used the Korotkoff method. When the ABPI values were
      calculated, the DINAMAP produced significantly higher median values than the
      Korotkoff (0.79 vs 0.72, p=0.003) and Doppler methods (0.79 vs 0.70, p<0.0001).
      The nurse had a higher median ABPI value of 0.76 compared with the doctor (0.71,
      p=0.01). CONCLUSION: This study shows that measurement of ABPI varies in
      different vascular units. The technique for ABPI measurement should be
      standardised.

PMID- 10906294
TI  - A comparison of colour duplex ultrasonography, papaverine testing and common
      femoral Doppler waveform analysis for assessment of the aortoiliac arteries.
AB  - OBJECTIVE: to study the "accuracy" of aortoiliac colour duplex ultrasonography.
      DESIGN: prospective study. SETTING: vascular laboratory, University Hospital.
      METHODS: a total of 25 aortoiliac stenoses were studied in 23 patients. For each
      iliac segment, colour duplex ultrasound, papaverine testing, hyperaemic common
      femoral Doppler waveform analysis and hyperaemic testing using a thigh pressure
      cuff were performed. A velocity ratio of two was used to indicate a significant
      50% diameter-reducing stenosis, but the velocity differences across stenoses as
      well as various characteristics of the hyyperaemic common femoral waveform were
      also studied. Retrospective receiver-operator characteristics and Kappa values
      were used for analysis. RESULTS: the Kappa agreement between ultrasonography and
      papaverine testing was 0.12 using peak systolic velocity ratios and 0.8 using
      hyperaemic peak systolic velocity differences. Hyperaemic common femoral
      pulsatility (PI) and resistance index (RI) both gained a Kappa level of 0.60. The
      reactive hyperaemia produced by a thigh cuff was more pronounced than that
      produced by papaverine. CONCLUSION: although the velocity ratio did not appear to
      perform well against the papaverine test, its apparent over-sensitivity calls
      into question the sensitivity of papaverine testing itself. The hyperaemic
      velocity difference at the stenosis or the hyperaemic PI or RI at common femoral
      level appear useful, non-invasive indicators of significant aortoiliac arterial
      disease.

PMID- 10906295
TI  - Iliac occlusions: stenting or crossover grafting? An examination of patency and
      cost.
AB  - OBJECTIVES: Percutaneous transluminal angioplasty with stenting is perceived to
      be a less invasive and cheaper option for the treatment of iliac artery occlusion
      than surgical reconstruction. We have carried out a prospective observational
      study of all patients undergoing an iliac stent or femorofemoral crossover graft
      for iliac artery occlusion to assess the cost effectiveness of the two approaches
      in a district general hospital. METHODS: Fifty-one patients underwent primary
      angioplasty with stenting and 87 patients crossover grafting. Patients were all
      assessed 2 months after their procedure and then at intervals over the following
      years. RESULTS: In 13 cases, it was impossible to place the stent successfully.
      In a further 10 patients, major complications occurred which were mainly
      thromboembolic. Fifteen patients underwent crossover grafting after failure to
      insert a stent, or after stent occlusion. No major complications occurred
      following crossover grafting. The median length of stay following successful
      stenting was 1 day; the following crossover grafting was 4 days. The mean stay
      was higher in each group (2.5 and 5.8 days) and is a more accurate parameter for
      estimation of cost, which for iliac stenting is estimated at pound1912 versus
      pound3072 for crossover grafting. The mean additional cost of those patients
      sustaining complications after stenting was pound2481. On an <<<<intention to
      treat>>>> basis, patency following stent insertion at 6 months was 52%; patency
      after bypass was 100% (p <0.0001). If any complication occurs after stenting, the
      cost advantage of the procedure is lost. In those patients without complication,
      the initial cost benefit of iliac stenting is lost within 6 months, as patients
      require further intervention, usually as a crossover graft, when the stent
      occludes. Crossover grafting is a durable low-risk procedure. CONCLUSIONS: We
      suggest that stenting of occluded iliac arteries should be reserved for those
      patients with limited life expectancy. Patients who are younger and fitter should
      be offered femorofemoral crossover grafting as a primary procedure until research
      enables identification of those patients who are most likely to maintain long
      term patency after stenting.

PMID- 10906296
TI  - Percutaneous catheter thrombus aspiration for acute or subacute arterial
      occlusion of the legs: how much thrombolysis is needed?
AB  - OBJECTIVE: To evaluate the role of a combined percutaneous endovascular approach
      including thrombus aspiration, catheter thrombolysis, and percutaneous
      transluminal angioplasty (PTA) to treat acute and subacute occlusions of native
      leg arteries. MATERIALS AND METHODS: Retrospective evaluation of the
      effectiveness and safety of this catheter therapy in 89 consecutive patients (93
      legs) in a single centre. RESULTS: Treatment was initially successful in 90% of
      legs. Mortality at 30 days was 8%, and at 12 months 19%. Amputation-free survival
      at 12 months was 78%. Aspiration alone was sufficient in 31% of cases, urokinase
      (mean dose 112 500+/-55 900 IU) was used in 22%, PTA was added in 69%. There was
      no major bleeding except for one false aneurysm treated by ultrasound-guided
      compression. Secondary interventions within 12 months were required in 30% of
      cases (14 endovascular, 16 open surgical procedures). CONCLUSIONS: Catheter
      thrombus aspiration in combination with thrombolysis and/or PTA is highly
      effective. Only in a minority of patients are thrombolytics in modest doses
      necessary, and serious bleeding complications are rare. We recommend this
      procedure as first-line treatment for acute or subacute infrainguinal arterial
      occlusions.

PMID- 10906297
TI  - Blunt injury to the common iliac artery.
AB  - OBJECTIVES AND DESIGN: iliac artery lesion after blunt trauma is uncommon, with
      only 12 previously reported cases. We report nine patients treated in two French
      teaching hospitals over a six-year period. Mechanism, symptomatology, treatment
      and outcome were analysed. MATERIAL AND METHOD: All patients were male with a
      mean (range) age of 29 (16-43) years. Median delay to operative repair was 15
      days. Through an extraperitoneal approach PTFE grafts were used in five cases and
      autogenous graft in four. RESULTS: Morbidity was 22%. Reoperation was necessary
      in two cases at a mean follow-up of 48 months, at which time all patients were
      asymptomatic with normal pulses. CONCLUSION: Clinicians should be alert to the
      possibility of this injury. An arteriography for Doppler ultrasound should be
      performed. Treatment is mainly surgical and produces excellent long-term results.

PMID- 10906298
TI  - Femorodistal PTFE bypass grafting for severe limb ischaemia: results of a
      prospective clinical study using a new distal anastomotic technique.
AB  - OBJECTIVES: To analyse graft patency and limb salvage following femorodistal
      bypass with ePTFE using a new distal anastomotic technique. Design prospective
      non-randomised study. MATERIAL AND METHODS: One hundred and twenty-nine patients
      (M:F; 2.23:1; mean age 65.2+/-10.0 years) underwent 135 operations for severe
      limb ischaemia. The new anastomosis, constructed entirely from ePTFE, was
      attached to the popliteal (21), anterior (46) and posterior (52) tibial, and
      peroneal (16) arteries. Cumulative primary (PPR) and secondary patency rates
      (SPR), limb salvage and survival were analysed using the Kaplan-Meier method.
      RESULTS: Median follow-up was 45 (range 6 to 72) months. There was no
      perioperative mortality. PPR and SPR at 1, 2, 3, 4, and 5 years were 63.0%,
      44.9%, 35.7%, 33.1% and 27.6% and 74.5%, 55.2%, 44.8%, 43.0%, and 37.6%,
      respectively. Cumulative limb salvage was 86.4%, 78.7%, and 73.2% at 1, 3, and 5
      years, respectively. CONCLUSIONS: This new anastomotic design was feasible and
      resulted in acceptable long-term results.

PMID- 10906299
TI  - Serum Lp(a) lipoprotein levels in patients with atherosclerotic occlusive disease
      of the lower extremities.
AB  - OBJECTIVE: To evaluate the association between Lp(a) lipoprotein levels, other
      serum lipids and the presence of lower limb atherosclerotic occlusive disease.
      MATERIALS AND METHODS: Angiographic findings in 36 patients were related to serum
      Lp(a). Total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol and
      Lp(a) levels were compared with those of 73 age- and sex-matched healthy
      controls. RESULTS: Atheromatous lesions were localised in the femoropopliteal (
      approximately 60%) and aortoiliac ( approximately 40%) segments. The number of
      stenosed arteries was > or =2 and the range of stenosis severity was between 40%
      and 100%. There was a significant increase in serum Lp(a) (p= 0.000001) and a
      decrease in serum HDL (p= 0.000009) levels in patients compared to controls. No
      difference was observed in total cholesterol, LDL-cholesterol or triglyceride.
      However, the ratio of total cholesterol/HDL-cholesterol was significantly higher
      (p= 0.005) in patients. CONCLUSION: A dyslipidaemic serum profile, characterised
      by increased Lp(a) levels and decreased HDL-cholesterol levels, is associated
      with atherosclerotic occlusive disease of the lower extremities.

PMID- 10906300
TI  - Association of sex with patency of femorodistal bypass grafts.
AB  - OBJECTIVE: There is evidence for superior patency in infra-inguinal bypass
      procedures in men compared to women. A large, prospectively planned series was
      investigated in order to confirm this finding and to determine the origin of this
      difference in outcome. METHODS: Patients underwent femorodistal bypass surgery
      and a prospectively planned 12-month follow-up. Outcomes in male and female
      patients were compared and investigated for associations with characteristics of
      the patients and the surgical procedures. RESULTS: A total of 517 patients
      received femorodistal bypass grafts, including 424 vein grafts and 93 prosthetic
      and vein-prosthetic composite grafts. Patency was confirmed to be higher in male
      than in female patients (56% vs. 42%, p=0.005). Fewer male patients received
      prosthetic or composite grafts (21% vs. 33%, p=0.005), but the difference in
      patency was evident only in patients receiving vein grafts. Female patients were
      smaller, included fewer smokers (p<0.001) and had worse symptoms (p=0.03), but
      none of these characteristics explained the difference in outcome. Patency in
      vein grafts was associated with graft diameter (p=0.004), but graft diameter was
      not significantly associated with sex (p=0.09) or with body size. CONCLUSIONS: It
      was confirmed that patency of femorodistal bypasses is significantly higher in
      males than females. None of the factors investigated here explain this
      difference, but the greater use of prosthetic and composite grafts in female
      patients suggests that poorer vein quality should be investigated as a possible
      source of the inferior outcome in female patients.

PMID- 10906301
TI  - Incidence of stenoses in femorodistal bypass vein grafts in a multicentre study.
AB  - OBJECTIVES: To establish the incidence of graft stenosis in a large population of
      patients undergoing femorodistal bypass procedures and to investigate the
      differences in incidence between individual surgical centres and other
      subpopulations. PATIENTS AND METHODS: A total of 277 patients with femorodistal
      bypasses underwent duplex scanning of vein grafts for 12 months for the detection
      of graft stenoses. A standard definition of a significant stenosis was used in
      all twenty participating centres. RESULTS: Overall stenosis rate was 27%.
      Stenoses were more common in composite vein grafts (43%) than in single segment
      vein grafts (25%) p=0.05. Stenoses were more common in female patients (38%) than
      males (22%) p=0.02. Stenosis rates in individual centres entering more than 20
      patients varied from 9% to 56%. In a multiple regression analysis only aspirin
      use, sex and centre were significant factors predicting the likelihood of graft
      stenosis. CONCLUSION: Female patients, those taking aspirin and patients with
      composite vein grafts appear to be more at risk of graft stenosis, but this does
      not fully explain wide variations in the incidence of stenoses reported by
      individual centres.

PMID- 10906302
TI  - Exercise training for claudicants: changes in blood flow, cardiorespiratory
      status, metabolic functions, blood rheology and lipid profile.
AB  - OBJECTIVE: Exercise training improves the walking distance of claudicants. The
      aim of this study was to investigate factors associated with the improvement in
      the maximum walking distance (MWD) in respect to cardiovascular, respiratory and
      metabolic adaptations. METHODS: Forty claudicants were studied. Common femoral
      artery blood flow (BF), heart rate (HR), oxygen consumption (VO(2)), respiratory
      exchange ratio (RER), lactate levels, blood rheology and lipid profiles were
      measured. Tests were repeated after 3 months of exercise training. RESULTS:
      Fifteen patients did not complete the exercise program. For patients who did
      complete the program, MWD improved by 82%. A significant reduction in HR and
      VO(2)during exercise was demonstrated. No significant changes occurred in BF or
      RER. Although MWD increased significantly, there was no increase in recovery
      VO(2)(oxygen debt). A significant reduction in post-exercise lactate levels
      occurred. Blood rheology was unchanged, but an improvement in HDL levels was
      noted. CONCLUSIONS: Many claudicants could not complete an exercise program,
      mainly due to osteoarthritis. Exercise training improved exercise tolerance
      significantly without any increase in BF. The HR and oxygen cost of similar
      exercise was reduced. An improved MWD did not correlate with a higher oxygen debt
      or lactate load. Favourable changes in lipid profiles occurred.

PMID- 10906303
TI  - Psychological consequences of screening for abdominal aortic aneurysm and
      conservative treatment of small abdominal aortic aneurysms.
AB  - OBJECTIVE: To describe the potential psychological consequences of screening for
      abdominal aortic aneurysms (AAAs). METHODS: The participants were prospectively
      and randomly sampled from a randomised screening trial for AAA and asked to
      complete a validated generic and global anonymous quality of life (QL)
      questionnaire by self-assessment (ScreenQL). Material case-control study:
      ScreenQL was completed once by 168 (48%) of 350 non-responders to screening, 271
      (81%) of 335 attenders before screening, 286 (85%) of 335 attenders after
      screening, 127 (85%) of 149 with a small AAA diagnosed at screening, and 231
      (66%) of 350 who were randomised not to be offered screening for AAA (controls).
      Prospective study (paired data): 127 men having a small AAA diagnosed. Twenty
      nine (81%) of 36 men operated after initial conservative treatment. RESULTS:
      Initially, the QL score was 5% lower among men with a small AAA compared to the
      controls (p<0.05), mainly because of poorer health perception. The QL score
      declined significantly further to 7% below control values during the period of
      conservative treatment. This impairment was mainly due to a 21% and 15% reduction
      in scores relating to health perception and psychosomatic distress, respectively.
      However, all scores improved to control levels in patients operated on. The QL of
      attending men for screening was significantly lower than that of the controls and
      the attenders after the screening. No differences were noticed concerning the non
      attenders. CONCLUSION: The offer of screening causes transient psychological
      stress in subjects found not to have AAA. However, diagnosis of an AAA seems to
      impair QL permanently and progressively in conservatively treated cases. This
      impairment seems reversible by operation. Nevertheless, the impairment seems
      considerable, and must be considered in the management of AAA and in the final
      evaluation of screening for AAA.

PMID- 10906304
TI  - Peroperative factors influencing the outcome of elective abdominal aorta aneurysm
      repair.
AB  - PURPOSE: To identify perioperative variables which may influence mortality of
      elective abdominal aneurysm repair (AAA). METHOD: prospective study of patients
      undergoing elective AAA repair between 1986 and 1997. RESULTS: Four hundred and
      seventy patients (438 men, 32 females) with a mean age of 69.4+/-13 years and
      aneurysms with a diameter of 60+/-3 mm were operated on with a 1-month mortality
      rate of 5.3%. Multivariate analysis identified the following independent risk
      factors for mortality: age >70 (p<0.0001), a past history of myocardial
      infarction (p<0.0001), preoperative renal insufficiency (p<0.0001), reoperation
      (p<0.0001), colonic necrosis (p<0.0001), and severe postoperative medical
      complications (p<0.0001). CONCLUSION: Intra- and postoperative events affect the
      outcome of AAA repair, independently of preoperative factors, and should be
      described when presenting the results of AAA repair.

PMID- 10906305
TI  - A prospective study of changes in aneurysm and graft length after endovascular
      exclusion of AAA using balloon and self-expanding endograft systems.
AB  - PURPOSE: Longitudinal shrinkage of aneurysms post-endovascular repair, employing
      unvalidated measurement techniques has been held to account for endograft
      disruption. In this study we record changes in aneurysm length, diameter and
      volume using the gold standard of calibrated spiral CT angiography (SCTA).
      METHOD: From 179 patients with AAA scanned by SCTA, 68 were selected for
      endografting. Twenty-seven had PTFE home-made prostheses while 41 patients had
      Talent endografts. SCTA was performed on the fifth postoperative day and 6
      monthly intervals thereafter. The distance between the lowest renal artery and
      the aortic bifurcation (VBL - vertical body length) and the luminal centre line
      length (LCL) were measured. Maximal sac diameters and volumes were recorded using
      3DCT reconstruction. RESULTS: Significant increase was noted in VBL (3.2) mm for
      PTFE-treated patients accompanied by an increase in sac volume at day 5 (12.5
      ml). No changes in LCL or maximal diameters were evident. At 1.5 years further
      lengthening of both VBL (6.4 mm) and LCL (9.3 mm) was unaccompanied by sac
      diameter/volume changes. Talent patients - no changes in VBL or LCL were evident.
      Volumes and maximal AP and transverse diameters showed marked shrinkage: AP -11.
      2 mm; transverse -2.6 mm; volumes by -35.5 ml at 6 months. CONCLUSION: With PTFE
      increase in VBL but not graft length, without concurrent changes in maximal
      diameters at day 5, is commensurate with increase in sac volume; after 1.5 years
      graft lengthening overtakes aortic lengthening. In Talent patients VBL/graft
      length remained unchanged. There is no evidence for longitudinal aneurysmal
      contracture. Volumes and maximal diameters for the Talent endograft but not for
      PTFE show shrinkage.

PMID- 10906306
TI  - Continued sac expansion in the absence of a demonstrable endoleak is an
      indication for secondary intervention.

PMID- 10906307
TI  - Successful surgical treatment of two patients with restenosis after previous
      stenting of the carotid artery.

PMID- 10906308
TI  - Economy-class syndrome presenting as phlegmasia caerulea dolens.

PMID- 10906309
TI  - Lumbar artery aneurysm associated with abdominal aortic aneurysm in a 72-year-old
      man.

PMID- 10906310
TI  - Multiple aneurysms in childhood - case report and review of the literature.

PMID- 10906311
TI  - How many maps are there in visual cortex?
AB  - In addition to a topographic map of the retina, mammalian visual cortex contains
      superimposed, orderly periodic maps of features such as orientation, eye
      dominance, direction of motion and spatial frequency. There is evidence that
      these maps are overlaid so as to ensure that all combinations of the different
      parameters are represented as uniformly as possible across visual space. However,
      it is unknown to what extent geometrical factors limit the number of periodic
      maps which might simultaneously be present, given this constraint. This paper
      attempts to investigate the question by using a dimension reduction model to
      generate maps of simple, many- dimensional feature spaces onto a model two
      dimensional cortex. The feature space included a model retina, plus N binary
      variables, corresponding to parameters such as ocular dominance or spatial
      frequency. The results suggest that geometrical factors do not sharply limit the
      ability of the cortex to represent combinations of parameters in spatially
      superimposed maps of similar periodicity. Considerations of uniform coverage
      suggest an upper limit of six or seven maps. A higher limit, of about nine or
      ten, may be imposed by the numbers of neurons (or minicolumns) available to
      represent each of 2(N) features within a given small region of cortex.

PMID- 10906312
TI  - The connections of layer 4 subdivisions in the primary visual cortex (V1) of the
      owl monkey.
AB  - The primary visual cortex (V1) of primates receives signals from parallel lateral
      geniculate nucleus (LGN) channels. These signals are utilized by the laminar and
      compartmental [i.e. cytochrome oxidase (CO) blob and interblob] circuitry of V1
      to synthesize new output pathways appropriate for the next steps of analysis.
      Within this framework, this study had two objectives: (i) to analyze the con-
      nections between primary input and output layers and compartments of V1; and (ii)
      to determine differences in connection patterns that might be related to species
      differences in physiological properties in an effort to link specific pathways to
      visual functions. In this study we examined the intrinsic interlaminar
      connections of V1 in the owl monkey, a nocturnal New World monkey, with a special
      emphasis on the projections from layer 4 to layer 3. Interlaminar connections
      were labeled via small iontophoretic or pressure injections of tracers
      [horseradish peroxidase, biocytin, biotinylated dextrine amine (BDA) or cholera
      toxin subunit B conjugated to colloidal gold particles]. Our most significant
      finding was that layer 4 (4C of Brodmann) can be divided into three tiers based
      upon projections to the superficial layers. Specifically, we find that 4alpha
      (4Calpha), 4beta (4Cbeta) and 4ctr send primary projections to layers 3C (4B),
      3Bbeta (4A) and 3Balpha (3B), respectively. Examination of laminar structure with
      Nissl staining supports a tripartite organization of layer 4. The cortical output
      layer above layer 3Balpha (3B) (e.g. layer 3A) does not appear to receive any
      direct connections from layer 4 but receives heavy input from layers 3Balpha (3B)
      and 3C (4B). Some connectional differences also were observed between the
      subdivisions of layer 3 and the infragranular layers. No consistent differences
      in connections were observed that distinguished CO blobs from interblobs or that
      could be correlated with differences in visual lifestyle (nocturnal versus
      diurnal) when compared with connectional data in other primates. Re-examination
      of data from previous studies in squirrel and macaque monkeys suggests that the
      tripartite organization of layer 4 and the unique projection pattern of layer
      4ctr are not restricted to owl monkeys, but are common to a number of primate
      species.

PMID- 10906314
TI  - Perceptual deficits after lesions of inferotemporal cortex in macaques.
AB  - This study used a novel approach to examine a much studied question, the nature
      of visual deficits caused by lesions of the inferotemporal cortex (IT). Unlike
      many previous studies of IT lesions, we de-emphasized early, non-specific
      disruptions of testing caused by the lesions, and instead concentrated on
      permanent changes in thresholds. This approach produced unexpected results that
      suggest a re-evaluation of the traditional view of the role of the IT cortex in
      shape perception and such related visual abilities as perceptual invariances,
      visual grouping, the visibility of illusory contours and the performance of
      oddity discriminations. In addition, the measurement of stable, post-lesion hue
      discrimination thresholds gave us a different perspective on the severity of
      color vision deficits which result from lesions of the IT cortex. We found that
      shape distortion thresholds were not permanently elevated by IT lesions and,
      indeed, showed no greater transitory disruption than did other visual abilities.
      This result is inconsistent with the common view that IT is critical to shape
      discriminations. Two other visual abilities that would be expected to be
      disrupted by IT lesions - the visual grouping of misoriented line segments and
      shape invariances (failure of irrelevant stimulus changes to disrupt shape
      distortion thresholds) - were not affected by IT lesions. However, shape
      discriminations based on illusory contours and some oddity discriminations were
      severely and permanently affected. Our results also showed that IT lesions caused
      permanent, moderate to large impairments of color vision, but not color
      blindness. Bilateral damage to area TEO caused no disruption of performance on
      any of the abovediscriminations. Our results suggest that the IT cortex in
      macaques may be critical to the visibility of illusory contours and the
      performance of some oddity discriminations, that it plays some role in color
      perception, but that it is not essential for shape, grouping discriminations or
      perceptual shape invariances.

PMID- 10906313
TI  - Moving illusory contours activate primary visual cortex: an fMRI study.
AB  - Identifying the cortical areas activated by illusory contours provides valuable
      information on the mechanisms of object perception. We applied functional
      magnetic resonance imaging to identify the visual areas of the human brain
      involved in the perception of a moving Kanizsa-type illusory contour. Our results
      indicate that, in addition to other cortical regions, areas V5 and V1 are
      activated. Activity in area V1 was particularly prominent.

PMID- 10906315
TI  - Myelination defects and neuronal hyperexcitability in the neocortex of connexin
      32-deficient mice.
AB  - Morphological and electrophysiological studies were performed on neocortices of
      adult Connexin 32 (Cx32)-deficient mice and wild-type mice to investigate the
      consequences of a lack of the gap junction subunit Cx32 on neocortical structure
      and function. Morphometrical analysis revealed a reduced volume fraction of
      myelin within the neuropil and a decreased thickness of the axonal myelin sheaths
      in the neocortex of Cx32-deficient mice. Intracellular recordings from neurons in
      neocortical slice preparations provided evidence for an increased membrane input
      resistance in neurons of Cx32-null mutant mice as compared to neurons of wild
      type mice. Consequently, neurons of Cx32-deficient mice displayed an enhanced
      intrinsic excitability. In addition, approximately 50% of the neurons
      investigated in slices of Cx32-deficient mice responded to afferent stimulation
      with delayed and large glutamatergic excitatory postsynaptic potentials
      resembling paroxysmal depolarizations. GABAergic inhibition sufficient to
      efficiently control synaptic excitability was virtually absent in these cells.
      The changes in intrinsic membrane properties observed in neurons of Cx32-null
      mutant mice were independent of the alterations in synaptic function, since
      increased membrane resistances were observed also in neurons with normal synaptic
      response pattern. Thus, in the neocortex, lack of Cx32 correlates with
      myelination defects, alterations in intrinsic membrane properties and dysfunction
      of inhibitory synaptic transmission.

PMID- 10906316
TI  - Segregating semantic and syntactic aspects of processing in the human brain: an
      fMRI investigation of different word types.
AB  - The processing of single words that varied in their semantic (concrete/abstract
      word) and syntactic (content/function word) status was investigated under
      different task demands (semantic/ syntactic task) in an event-related functional
      magnetic resonance imaging experiment. Task demands to a large degree determined
      which subparts of the neuronal network supporting word processing were activated.
      Semantic task demands selectively activated the left pars triangularis of the
      inferior frontal gyrus (BA 45) and the posterior part of the left middle/superior
      temporal gyrus (BA 21/22/37). In contrast, syntactic processing requirements led
      to an increased activation in the inferior tip of the left frontal operculum (BA
      44) and the cortex lining the junction of the inferior frontal and inferior
      precentral sulcus (BA 44/6). Moreover, for these latter areas a word class by
      concreteness interaction was observed when a syntactic judgement was required.
      This interaction can be interpreted as a prototypicality effect: non-prototypical
      members of a word class, i.e. concrete function words and abstract content words,
      showed a larger activation than prototypical members, i.e. abstract function
      words and concrete content words. The combined data suggest that the activation
      pattern underlying word processing is predicted neither by syntactic class nor
      semantic concreteness but, rather, by task demands focusing either on semantic or
      syntactic aspects. Thus, our findings that semantic and syntactic aspects of
      processing are both functionally distinct and involve different subparts of the
      neuronal network underlying word processing support a domain-specific
      organization of the language system.

PMID- 10906317
TI  - Maintaining and shifting attention within left or right hemifield.
AB  - Positron emission tomography (PET) was used to examine two questions: (i) which
      structures of the intact human brain change their activity with the direction of
      attention to left or right visual field; and (ii) how does activity in these
      structures, and in parietal cortex in particular, depend on the frequency of
      attentional shifts? Subjects were required to discriminate the orientation of
      peripheral gratings. The two main experimental variables were the attended
      hemifield (left or right) and the proportion of trials requiring a shift within
      that hemifield (20% or 80%). A detection control condition was also included.
      Behaviourally, subjects were less accurate and significantly slower when a trial
      required a shift than when it did not. Ventral and lateral occipital areas showed
      significantly higher blood flow levels contralateral to the direction of
      attention. Replicating previous work, there was also a significant main effect of
      the direction of attention in left lateral prefrontal cortex: blood flow levels
      were higher during leftward attention in comparison both to baseline and to
      rightward attention. This left frontal effect reached significance in single
      subjects in whom several activation sites could be distinguished within left
      middle and inferior frontal gyrus. Right and left parietal cortex were activated
      during both left- and right-field attention conditions, with a tendency for
      higher activity levels when attention was directed contralaterally. Contrary to
      the experimental hypothesis, however, parietal regions were not activated
      differentially by high versus low numbers of attentional shifts. The current
      experiment confirms that left frontal convexity is sensitive to manipulations of
      the direction of visuospatial attention. The results do not indicate a specific
      role of parietal cortex in attentional shifting.

PMID- 10906318
TI  - Congenital auditory deprivation reduces synaptic activity within the auditory
      cortex in a layer-specific manner.
AB  - The present study investigates the functional deficits of naive auditory cortices
      in adult congenitally deaf cats. For this purpose, their auditory system was
      stimulated electrically using cochlear implants. Synaptic currents in cortical
      layers were revealed using current source density analyses. They were compared
      with synaptic currents found in electrically stimulated hearing cats. The naive
      auditory cortex showed significant deficits in synaptic activity in infragranular
      cortical layers. Furthermore, there was also a deficit of synaptic activities at
      longer latencies (>30 ms). The 'cortical column' was not activated in the well
      defined sequence found in normal hearing cats. These results demonstrate
      functional deficits as a consequence of congenital auditory deprivation. Similar
      deficits are likely in congenitally deaf children.

PMID- 10906319
TI  - Matching two imagined clocks: the functional anatomy of spatial analysis in the
      absence of visual stimulation

PMID- 10906320
TI  - Flavopiridol inhibits P-TEFb and blocks HIV-1 replication.
AB  - Flavopiridol (L86-8275, HMR1275) is a cyclin-dependent kinase (Cdk) inhibitor
      that is in clinical trials as a cancer treatment because of its antiproliferative
      properties. We found that the flavonoid potently inhibited transcription by RNA
      polymerase II in vitro by blocking the transition into productive elongation, a
      step controlled by P-TEFb. The ability of P-TEFb to phosphorylate the carboxyl
      terminal domain of the large subunit of RNA polymerase II was inhibited by
      flavopiridol with a K(i) of 3 nm. Interestingly, the drug was not competitive
      with ATP. P-TEFb composed of Cdk9 and cyclin T1 is a required cellular cofactor
      for the human immunodeficiency virus (HIV-1) transactivator, Tat. Consistent with
      its ability to inhibit P-TEFb, flavopiridol blocked Tat transactivation of the
      viral promoter in vitro. Furthermore, flavopiridol blocked HIV-1 replication in
      both single-round and viral spread assays with an IC(50) of less than 10 nm.

PMID- 10906321
TI  - Novel mechanism of surface catalysis of protein adduct formation. NMR studies of
      the acetylation of ubiquitin.
AB  - Reactivity of surface lysyl residues of proteins with a broad range of chemical
      agents has been proposed to be dependent on the catalytic microenvironment of the
      residue. We have investigated the acetylation of wild type ubiquitin and of the
      UbH68N mutant to evaluate the potential contribution of His-68 to the reactivity
      of Lys-6, which is about 4 A distant. These studies were performed using [1
      (13)C]acetyl salicylate or [1,1'-(13)C(2)]acetic anhydride, and the acetylated
      products were detected by two-dimensional heteronuclear multiple quantum
      coherence spectroscopy. The results demonstrate that His-68 makes a positive
      contribution to the rate of acetylation of Lys-6 by labeled aspirin.
      Additionally, a pair of transient resonances is observed after treatment of wild
      type ubiquitin with the labeled acetic anhydride but not upon treatment of the
      H68N mutant. These resonances are assigned to the acetylated His-68 residue. The
      loss of intensity of the acetylhistidine resonances is accompanied by an increase
      in intensity of the acetyl-Lys-6 peak, supporting the existence of a
      transacetylation process between the acetylhistidine 68 and lysine 6 residues
      located on the protein surface. Hence, this may be the first direct demonstration
      of a catalytic intermediate forming on the protein surface.

PMID- 10906322
TI  - C/EBP regulates hepatic transcription of 11beta -hydroxysteroid dehydrogenase
      type 1. A novel mechanism for cross-talk between the C/EBP and glucocorticoid
      signaling pathways.
AB  - Glucocorticoid action within individual cells is potently modulated by 11beta
      hydroxysteroid dehydrogenase (11beta-HSD), which, by interconverting active and
      inert glucocorticoids, determines steroid access to receptors. Type 1 11beta-HSD
      (11beta-HSD1) is highly expressed in liver where it regenerates glucocorticoids,
      thus amplifying their action and contributing to induction of glucocorticoid
      responsive genes, most of which are also regulated by members of the C/EBP
      (CAAT/enhancer-binding protein) family of transcription factors. Here we
      demonstrate that C/EBPalpha is a potent activator of the 11beta-HSD1 gene in
      hepatoma cells and that mice deficient in C/EBPalpha have reduced hepatic 11beta
      HSD1 expression. In contrast, C/EBPbeta is a relatively weak activator of 11beta
      HSD1 transcription in hepatoma cells and attenuates C/EBPalpha induction, and
      mice that lack C/EBPbeta have increased hepatic 11beta-HSD1 mRNA. The 11beta-HSD1
      promoter (between -812 and +76) contains 10 C/EBP binding sites, and mutation of
      the promoter proximal sites decreases the C/EBP inducibility of the promoter. One
      site encompasses the transcription start, and both C/EBPalpha and C/EBPbeta are
      present in complexes formed by liver nuclear proteins at this site. The
      regulation of 11beta-HSD1 expression, and hence intracellular glucocorticoid
      levels, by members of the C/EBP family provides a novel mechanism for cross-talk
      between the C/EBP family of transcription factors and the glucocorticoid
      signaling pathway.

PMID- 10906323
TI  - Activation of mitogen-activated protein kinase cascade regulates pituitary tumor
      transforming gene transactivation function.
AB  - Pituitary tumor-transforming gene (PTTG) is a recently characterized oncogene
      that can act as a transcriptional activator. In this study, we have characterized
      the transactivation domain of PTTG. Transient transfection of fusion constructs
      containing GAL4 DNA-binding domain and different parts of PTTG indicated the
      transactivation domain of PTTG is located between amino acids 119 and 164.
      Mitogen-activated protein (MAP) kinase cascade is important in the regulation of
      cell growth, apoptosis, and differentiation. Therefore, we have explored the
      possibility that this kinase cascade plays a role in regulating PTTG
      transactivation function. Activation of the MAP kinase cascade by epidermal
      growth factor or an expression vector for a constitutively active form of the MAP
      kinase kinase (MEK1) led to stimulation of PTTG transactivation activity. We
      showed that PTTG is phosphorylated in vitro on Ser(162) by MAP kinase and that
      this phosphorylation site plays an essential role in PTTG transactivation
      function. We demonstrated that PTTG interacts directly with MEK1 through a
      putative SH3 domain-binding site located between amino acids 51 and 54 and that
      this interaction is crucial for PTTG transactivation function. In addition, we
      showed that activation of MAP kinase phosphorylation cascade resulted in nuclear
      translocation of PTTG. Together, our data establish that a growth factor
      stimulated MAP kinase plays an important role in modulating PTTG function.

PMID- 10906324
TI  - The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha
      and beta integrin chains and is recruited to adhesion complexes.
AB  - LIM proteins contain one or more double zinc finger structures (LIM domains)
      mediating specific contacts between proteins that participate in the formation of
      multiprotein complexes. We report that the LIM-only protein DRAL/FHL2, with four
      and a half LIM domains, can associate with alpha(3A), alpha(3B), alpha(7A), and
      several beta integrin subunits as shown in yeast two-hybrid assays as well as
      after overexpression in human cells. The amino acid sequence immediately
      following the conserved membrane-proximal region in the integrin alpha subunits
      or the C-terminal region with the conserved NXXY motif of the integrin beta
      subunits are critical for binding DRAL/FHL2. Furthermore, the DRAL/FHL2
      associates with itself and with other molecules that bind to the cytoplasmic
      domain of integrin alpha subunits. Deletion analysis of DRAL/FHL2 revealed that
      particular LIM domains or LIM domain combinations bind the different proteins.
      These results, together with the fact that full-length DRAL/FHL2 is found in cell
      adhesion complexes, suggest that it is an adaptor/docking protein involved in
      integrin signaling pathways.

PMID- 10906325
TI  - The lipid-associated conformation of the low density lipoprotein receptor binding
      domain of human apolipoprotein E.
AB  - Apolipoprotein E (apoE) is a 34-kDa exchangeable apolipoprotein that regulates
      metabolism of plasma lipoproteins by functioning as a ligand for members of the
      LDL receptor family. The receptor-binding region localizes to the vicinity of
      residues 130-150 within its independently folded 22-kDa N-terminal domain. In the
      absence of lipid, this domain exists as a receptor-inactive, globular four-helix
      bundle. Receptor recognition properties of this domain are manifest upon lipid
      association, which is accompanied by a conformational change in the protein.
      Fluorescence resonance energy transfer has been used to monitor helix
      repositioning, which accompanies lipid association of the apoE N-terminal domain.
      Site-directed mutagenesis was used to replace naturally occurring Trp residues
      with phenylalanine, creating a Trp-null apoE3 N-terminal domain (residues 1-183).
      Subsequently, tyrosine residues in helix 2, helix 3, or helix 4 were converted to
      Trp, generating single Trp mutant proteins. The lone cysteine at position 112 was
      covalently modified with N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine,
      which serves as an energy acceptor from excited tryptophan residues. Fluorescence
      resonance energy transfer analysis of apoE N-terminal domain variants in
      phospholipid disc complexes suggests that the helix bundle opens to adopt a
      partially extended conformation. A model is presented that depicts a tandem
      arrangement of the receptor-binding region of the protein in the disc complex,
      corresponding to its low density lipoprotein receptor-active conformation.

PMID- 10906326
TI  - Unique structural and functional properties of the ATP-binding domain of atypical
      protein kinase C-iota.
AB  - Atypical protein kinase C-iota (aPKCiota) plays an important role in mitogenic
      signaling, actin cytoskeleton organization, and cell survival. Apart from the
      differences in the regulatory domain, the catalytic domain of aPKCiota differs
      considerably from other known kinases, because it contains a modification within
      the glycine-rich loop motif (GXGXXG) that is found in the nucleotide-binding fold
      of virtually all nucleotide-binding proteins including PKCs, Ras, adenylate
      kinase, and the mitochondrial F1-ATPase. We have used site-directed mutagenesis
      and kinetic analysis to investigate whether these sequence differences affect the
      nucleotide binding properties and catalytic activity of aPKCiota. When lysine
      274, a residue essential for ATP binding and activity conserved in most protein
      kinases, was replaced by arginine (K274R mutant), aPKCiota retained its normal
      kinase activity. This is in sharp contrast to results published for any other PKC
      or even distantly related kinases like phosphoinositide 3-kinase gamma, where the
      same mutation completely abrogated the kinase activity. Furthermore, the
      sensitivity of aPKCiota for inhibition by GF109203X, a substance acting on the
      ATP-binding site, was not altered in the K274R mutant. In contrast, replacement
      of Lys-274 by tryptophan (K274W) completely abolished the kinase activity of
      PKCiota. In accordance with results obtained with other kinase-defective PKC
      mutants, in cultured cells aPKCiota-K274W acted in a dominant negative fashion on
      signal transduction pathways involving endogenous aPKCiota, whereas the effect of
      the catalytically active K274R mutant was identical to the wild type enzyme. In
      summary, aPKCiota differs from classical and novel PKCs also in the catalytic
      domain. This information could be of significant value for the development of
      specific inhibitors of aPKCiota as a key factor in central signaling pathways.

PMID- 10906329
TI  - Cold adaptation of a mesophilic subtilisin-like protease by laboratory evolution.
AB  - Enzymes isolated from organisms native to cold environments generally exhibit
      higher catalytic efficiency at low temperatures and greater thermosensitivity
      than their mesophilic counterparts. In an effort to understand the evolutionary
      process and the molecular basis of cold adaptation, we have used directed
      evolution to convert a mesophilic subtilisin-like protease from Bacillus
      sphaericus, SSII, into its psychrophilic counterpart. A single round of random
      mutagenesis followed by recombination of improved variants yielded a mutant,
      P3C9, with a catalytic rate constant (k(cat)) at 10 degrees C 6.6 times and a
      catalytic efficiency (k(cat)/K(M)) 9.6 times that of wild type. Its half-life at
      70 degrees C is 3.3 times less than wild type. Although there is a trend toward
      decreasing stability during the progression from mesophile to psychrophile, there
      is not a strict correlation between decreasing stability and increasing low
      temperature activity. A first generation mutant with a >2-fold increase in k(cat)
      is actually more stable than wild type. This suggests that the ultimate decrease
      in stability may be due to random drift rather than a physical incompatibility
      between low temperature activity and high temperature stability. SSII shares 77.
      4% identity with the naturally psychrophilic protease subtilisin S41. Although
      SSII and S41 differ at 85 positions, four amino acid substitutions were
      sufficient to generate an SSII whose low temperature activity is greater than
      that of S41. That none of the four are found in S41 indicates that there are
      multiple routes to cold adaptation.

PMID- 10906327
TI  - Characterization of determinants for the specificity of Arabidopsis thioredoxins
      h in yeast complementation.
AB  - The disruption of the two thioredoxin genes in Saccharomyces cerevisiae leads to
      a complex phenotype, including the inability to use methionine sulfoxide as
      sulfur source, modified cell cycle parameters, reduced H(2)O(2) tolerance, and
      inability to use sulfate as sulfur source. Expression of one of the multiple
      Arabidopsis thaliana thioredoxins h in this mutant complements only some aspects
      of the phenotype, depending on the expressed thioredoxin: AtTRX2 or AtTRX3 induce
      methionine sulfoxide assimilation and restore a normal cell cycle. In addition
      AtTRX2 also confers growth on sulfate but no H(2)O(2) tolerance. In contrast,
      AtTRX3 does not confer growth on sulfate but induces H(2)O(2) tolerance. We have
      constructed hybrid proteins between these two thioredoxins and show that all
      information necessary for sulfate assimilation is present in the C-terminal part
      of AtTRX2, whereas some information needed for H(2)O(2) tolerance is located in
      the N-terminal part of AtTRX3. In addition, mutation of the atypical redox active
      site WCPPC to the classical site WCGPC restores some growth on sulfate. All these
      data suggest that the multiple Arabidopsis thioredoxins h originate from a
      totipotent ancestor with all the determinants necessary for interaction with the
      different thioredoxin target proteins. After duplications each member evolved by
      losing or masking some of the determinants.

PMID- 10906330
TI  - Substrate specificity of human collagenase 3 assessed using a phage-displayed
      peptide library.
AB  - The substrate specificity of human collagenase 3 (MMP-13), a member of the matrix
      metalloproteinase family, is investigated using a phage-displayed random
      hexapeptide library containing 2 x 10(8) independent recombinants. A total of 35
      phage clones that express a peptide sequence that can be hydrolyzed by the
      recombinant catalytic domain of human collagenase 3 are identified. The
      translated DNA sequence of these clones reveals highly conserved putative P1, P2,
      P3 and P1', P2', and P3' subsites of the peptide substrates. Kinetic analysis of
      synthetic peptide substrates made from human collagenase 3 selected phage clones
      reveals that some of the substrates are highly active and selective. The most
      active substrate, 2, 4-dinitrophenyl-GPLGMRGL-NH(2) (CP), has a k(cat)/K(m) value
      of 4.22 x 10(6) m(-)(1) s(-)(1) for hydrolysis by collagenase 3. CP was
      synthesized as a consensus sequence deduced from the preferred subsites of the
      aligned 35 phage clones. Peptide substrate CP is 1300-, 11-, and 820-fold
      selective for human collagenase 3 over the MMPs stromelysin-1, gelatinase B, and
      collagenase 1, respectively. In addition, cleavage of CP is 37-fold faster than
      peptide NF derived from the major MMP-processing site in aggrecan. Phage display
      screening also selected five substrate sequences that share sequence homology
      with a major MMP cleavage sequence in aggrecan and seven substrate sequences that
      share sequence homology with the primary collagenase cleavage site of human type
      II collagen. In addition, putative cleavage sites similar to the consensus
      sequence are found in human type IV collagen. These findings support previous
      observations that human collagenase 3 can degrade aggrecan, type II and type IV
      collagens.

PMID- 10906331
TI  - Isolation and cloning of four subunits of a fission yeast TFIIIC complex that
      includes an ortholog of the human regulatory protein TFIIICbeta.
AB  - Eukaryotic tRNA genes are controlled by proximal and downstream elements that
      direct transcription by RNA polymerase (pol) III. Transcription factors (TFs)
      that reside near the initiation site are related in Saccharomyces cerevisiae and
      humans, while those that reside at or downstream of the B box share no
      recognizable sequence relatedness. Human TFIIICbeta is a transcriptional
      regulator that exhibits no homology to S. cerevisiae sequences on its own. We
      cloned an essential Schizosaccharomyces pombe gene that encodes a protein, Sfc6p,
      with homology to the S. cerevisiae TFIIIC subunit, TFC6p, that extends to human
      TFIIICbeta. We also isolated and cloned S. pombe homologs of three other TFIIIC
      subunits, Sfc3p, Sfc4p, and Sfc1p, the latter two of which are conserved from S.
      cerevisiae to humans, while the former shares homology with the S. cerevisiae B
      box-binding homolog only. Sfc6p is a component of a sequence-specific DNA-binding
      complex that also contains the B box-binding homolog, Sfc3p. Immunoprecipitation
      of Sfc3p further revealed that Sfc1p, Sfc3p, Sfc4p, and Sfc6p are associated in
      vivo and that the isolated Sfc3p complex is active for pol III-mediated
      transcription of a S. pombe tRNA gene in vitro. These results establish a link
      between the downstream pol III TFs in yeast and humans.

PMID- 10906332
TI  - Grp78 is involved in retention of mutant low density lipoprotein receptor protein
      in the endoplasmic reticulum.
AB  - The low density lipoprotein (LDL) receptor is responsible for removing the
      majority of the LDL cholesterol from the plasma. Mutations in the LDL receptor
      gene cause the disease familial hypercholesterolemia (FH). Approximately 50% of
      the mutations in the LDL receptor gene in patients with FH lead to receptor
      proteins that are retained in the endoplasmic reticulum (ER). Misfolding of
      mutant LDL receptors is a probable cause of this ER retention, resulting in no
      functional LDL receptors at the cell surface. However, the specific factors and
      mechanisms responsible for retention of mutant LDL receptors are unknown. In the
      present study we show that the molecular chaperone Grp78/BiP co
      immunoprecipitates with both the wild type and two different mutant (W556S and
      C646Y) LDL receptors in lysates obtained from human liver cells overexpressing
      wild type or mutant LDL receptors. A pulse-chase study shows that the interaction
      between the wild type LDL receptor and Grp78 is no longer detectable after 2(1/2)
      h, whereas it persists for more than 4 h with the mutant receptors. Furthermore,
      about five times more Grp78 is co-immunoprecipitated with the mutant receptors
      than with the wild type receptor suggesting that Grp78 is involved in retention
      of mutant LDL receptors in the ER. Overexpression of Grp78 causes no major
      alterations on the steady state level of active LDL receptors at the cell
      surface. However, overexpression of Grp78 decreases the processing rate of newly
      synthesized wild type LDL receptors. This indicates that the Grp78 interaction is
      a rate-limiting step in the maturation of the wild type LDL receptor and that
      Grp78 may be an important factor in the quality control of newly synthesized LDL
      receptors.

PMID- 10906335
TI  - Preparation and crystallization of dynamic NF-kappa B.Ikappa B complexes.
AB  - The formation of single, well-diffracting crystals is a requirement for any
      molecular structure determination by x-ray crystallography. Crystallization of
      biological macromolecules can represent a significant obstacle when the subject
      exhibits internal flexibility or indiscriminate self-association. In such cases,
      the removal of inherently flexible regions and the addition of stabilizing
      ligands can improve the probability of crystal formation and ordered growth. We
      have applied these principles in order to form crystals of the Rel homology
      region of transcription factor NF-kappaB in complex with its inhibitors
      IkappaBalpha and IkappaBbeta. None of these molecules crystallizes in the absence
      of a binding partner. Recombinant overexpression of truncated IkappaBalpha
      required selection of the correct start site. NF-kappaB.IkappaBalpha complex
      crystals formed under relatively stringent conditions. NF-kappaB. IkappaBbeta
      complex crystals were formed by analogy to NF-kappaB. IkappaBalpha, although some
      modifications in purification and complex formation were necessary due to
      differences between the inhibitors.

PMID- 10906333
TI  - Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1) splice
      variant encoding a truncated receptor.
AB  - We have identified a splice variant encoding only the extracellular ligand
      binding domain of the gamma-aminobutyric acid B (GABA(B)) receptor subunit
      GABA(B(1a)). This isoform, which we have named GABA(B(1e)), is detected in both
      rats and humans. While GABA(B(1e)) is a minor component of the total pool of
      GABA(B(1)) transcripts detected in the central nervous system, it is the primary
      isoform found in all peripheral tissues examined. When expressed in a
      heterologous system, the truncated receptor is both secreted and membrane
      associated. However, GABA(B(1e)) lacks the ability to bind the radiolabeled
      antagonist [(3)H]CGP 54626A, activate G-protein coupled inwardly rectifying
      potassium channels, or inhibit forskolin-induced cAMP production when it is
      expressed alone or together with GABA(B(2)). Interestingly, when co-expressed
      with GABA(B(2)), not only does the truncated receptor heterodimerize with
      GABA(B(2)), the association is of sufficient avidity to disrupt the normal
      GABA(B(1a))/GABA(B(2)) association. Despite this strong interaction, GABA(B(1e))
      fails to disrupt G-protein coupled inwardly rectifying potassium activation by
      the full-length heterodimer pair of GABA(B(1a))/GABA(B(2)).

PMID- 10906334
TI  - Antisense RNA-mediated deficiency of the calpain protease, nCL-4, in NIH3T3 cells
      is associated with neoplastic transformation and tumorigenesis.
AB  - We previously have described the use of an antisense RNA strategy termed random
      homozygous knock-out (RHKO) to identify negative regulators of cell
      proliferation. Here we report the discovery that RHKO-mediated deficiency of the
      nCL-4 calpain protease results in cellular transformation of and tumorigenesis by
      murine NIH3T3 fibroblasts. We isolated cell clones able to form colonies on 0.5%
      soft agar and found that these cells generated tumors when injected
      subcutaneously into nude mice. The gene inactivated by RHKO was identified as nCL
      4 by genomic library screening, transcript analysis, and DNA sequencing.
      Anchorage-independent growth, as indicated by colony formation on soft agar, was
      reversed by reversal of antisense-mediated homozygous inactivation, but continued
      haplo-insufficiency of nCL-4 resulting from insertional mutagenesis of one nCL-4
      allele was associated with persistent tumorigenesis. nCL-4 cDNA expressed in
      naive 3T3 cells in the antisense, but not sense, direction under control of the
      cytomegalovirus early promoter reproduced the anchorage-independent growth
      effects of RHKO. Our results implicate deficiency of the nCL-4 calpain protease
      in neoplastic transformation.

PMID- 10906336
TI  - The structure of human beta-defensin-2 shows evidence of higher order
      oligomerization.
AB  - Defensins are small cationic peptides that are crucial components of innate
      immunity, serving as both antimicrobial agents and chemoattractant molecules. The
      specific mechanism of antimicrobial activity involves permeabilization of
      bacterial membranes. It has been postulated that individual monomers oligomerize
      to form a pore through anionic membranes, although the evidence is only indirect.
      Here, we report two high resolution x-ray structures of human beta-defensin-2
      (hBD2). The phases were experimentally determined by the multiwavelength
      anomalous diffraction method, utilizing a novel, rapid method of derivatization
      with halide ions. Although the shape and charge distribution of the monomer are
      similar to those of other defensins, an additional alpha-helical region makes
      this protein topologically distinct from the mammalian alpha- and beta-defensin
      structures reported previously. hBD2 forms dimers topologically distinct from
      that of human neutrophil peptide-3. The quaternary octameric arrangement of hBD2
      is conserved in two crystal forms. These structures provide the first detailed
      description of dimerization of beta-defensins, and we postulate that the mode of
      dimerization of hBD2 is representative of other beta-defensins. The structural
      and electrostatic properties of the hBD2 octamer support an electrostatic charge
      based mechanism of membrane permeabilization by beta-defensins, rather than a
      mechanism based on formation of bilayer-spanning pores.

PMID- 10906337
TI  - Different sensitivity of the transforming growth factor-beta cell cycle arrest
      pathway to c-Myc and MDM-2.
AB  - Recently, the oncoprotein MDM-2 was implicated in the transforming growth factor
      beta (TGF-beta) growth inhibitory pathway by the finding that prolonged,
      constitutive expression of MDM-2 in mink lung epithelial cells could overcome the
      antiproliferative effect of TGF-beta (Sun, P., Dong, P., Dai, K., Hannon, G. J.,
      and Beach, D. (1998) Science 282, 2270-2272). However, using Mv1Lu cells
      conditionally expressing MDM-2, we found that MDM-2 does not overcome TGF-beta
      mediated growth arrest. No detectable changes were observed in various TGF-beta
      responses, including cell cycle arrest, activation of transcriptional reporters,
      and TGF-beta-dependent Smad2/3 nuclear accumulation. This finding was in direct
      contrast to the effect of forcing c-Myc expression, a bona fide member of the TGF
      beta growth inhibitory pathway, which renders cells refractory to TGF-beta
      induced cell cycle arrest. Our results suggest that an MDM-2-dependent increase
      in cell cycle progression may allow the acquisition of additional mutations over
      time and that these alterations then allow cells to evade a TGF-beta-mediated
      growth arrest. Our conclusion is that, whereas c-Myc down-regulation by TGF-beta
      is a required event in the cell cycle arrest response of epithelial cells, MDM-2
      is not a direct participant in the normal TGF-beta antiproliferative response.

PMID- 10906338
TI  - Tyrosine nitration by peroxynitrite formed from nitric oxide and superoxide
      generated by xanthine oxidase.
AB  - Peroxynitrite (ONOO(-)) is a potent nitrating and oxidizing agent that is formed
      by a rapid reaction of nitric oxide (NO) with superoxide anion (O(2)). It appears
      to be involved in the pathophysiology of many inflammatory and neurodegenerative
      diseases. It has recently been reported (Pfeiffer, S., and Mayer, B. (1998) J.
      Biol. Chem. 273, 27280-27285) that ONOO(-) generated at neutral pH from NO and
      O(2) (NO/O(2)) was substantially less efficient than preformed ONOO(-) at
      nitrating tyrosine. Here we re-evaluated tyrosine nitration by NO/O(2) with a
      shorter incubation period and a more sensitive electrochemical detection system.
      Appreciable amounts of nitrotyrosine were produced by ONOO(-) formed in situ (2.9
      micrometer for 5 min; 10 nm/s) by NO/O(2) flux obtained from propylamine NONOate
      (CH(3)N[N(O)NO](-) (CH(2))(3)NH(2)(+)CH(3)) and xanthine oxidase using pterin as
      a substrate in phosphate buffer (pH 7.0) containing 0.1 mm l-tyrosine. The yield
      of nitrotyrosine by this NO/O(2) flux was approximately 70% of that produced by
      the same flux of preformed ONOO(-) (2.9 micrometer/5 min). When hypoxanthine was
      used as a substrate, tyrosine nitration by NO/O(2) was largely eliminated because
      of the inhibitory effect of uric acid produced during the oxidation of
      hypoxanthine. Tyrosine nitration caused by NO/O(2) was inhibited by the ONOO(-)
      scavenger ebselen and was enhanced 2-fold by NaHCO(3), as would be expected,
      because CO(2) promotes tyrosine nitration. The profile of nitrotyrosine and
      dityrosine formation produced by NO/O(2) flux (2.9 micrometer/5 min) was
      consistent with that produced by preformed ONOO(-). Tyrosine nitration
      predominated compared with dityrosine formation caused by a low nanomolar flux of
      ONOO(-) at physiological concentrations of free tyrosine (<0.5 mm). In
      conclusion, our results show that NO generated with O(2) nitrates tyrosine with a
      reactivity and efficacy similar to those of chemically synthesized ONOO(-),
      indicating that ONOO(-) can be a significant source of tyrosine nitration in
      physiological and pathological events in vivo.

PMID- 10906339
TI  - Unusual pressure effects on ligand rebinding to the human myoglobin Leucine 29
      mutants.
AB  - Using high pressure flash photolysis, we revealed that the side chain of Leu(29)
      controls the reaction volume of the ligand migration process in myoglobin, which
      is the primary factor for the unusual activation volume of ligand binding in some
      Leu(29) mutants. As we previously reported (Adachi, S., Sunohara, N., Ishimori,
      K., and Morishima, I. (1992) J. Biol. Chem. 267, 12614-12621), CO bimolecular
      rebinding in the L29A mutant was unexpectedly decelerated by pressurization,
      suggesting that the rate-determining step is switched to ligand migration.
      However, very slow CO bimolecular rebinding of the mutants implies that bond
      formation is still the rate-determining step. To gain further insights into
      effects of the side chain on ligand binding, we prepared some new Leu(29) mutants
      to measure the CO and O(2) rebinding reaction rates under high hydrostatic
      pressure. CO bimolecular rebinding in the mutants bearing Gly or Ser at position
      29 was also decelerated upon pressurization, resulting in apparent positive
      activation volumes (DeltaV), as observed for O(2) binding. Based on the three
      state model, we concluded that the increased space available to ligands in these
      mutants enhances the volume difference between the geminate and deoxy states
      (DeltaV(32)), which shifts the apparent activation volume to the positive side,
      and that the apparent positive activation volume is not due to contribution of
      the ligand migration process to the rate-determining step.

PMID- 10906340
TI  - Superoxide reacts with nitric oxide to nitrate tyrosine at physiological pH via
      peroxynitrite.
AB  - Tyrosine nitration is a widely used marker of peroxynitrite (ONOO(-)) produced
      from the reaction of nitric oxide with superoxide. Pfeiffer and Mayer (Pfeiffer,
      S., and Mayer, B. (1998) J. Biol. Chem. 273, 27280-27285) reported that
      superoxide produced from hypoxanthine plus xanthine oxidase in combination with
      nitric oxide produced from spermine NONOate did not nitrate tyrosine at neutral
      pH. They suggested that nitric oxide and superoxide at neutral pH form a less
      reactive intermediate distinct from preformed alkaline peroxynitrite that does
      not nitrate tyrosine. Using a stopped-flow spectrophotometer to rapidly mix
      potassium superoxide with nitric oxide at pH 7.4, we report that an intermediate
      spectrally and kinetically identical to preformed alkaline cis-peroxynitrite was
      formed in 100% yield. Furthermore, this intermediate nitrated tyrosine in the
      same yield and at the same rate as preformed peroxynitrite. Equivalent
      concentrations of nitric oxide under aerobic conditions in the absence of
      superoxide did not produce detectable concentrations of nitrotyrosine. Carbon
      dioxide increased the efficiency of nitration by nitric oxide plus superoxide to
      the same extent as peroxynitrite. In experiments using xanthine oxidase as a
      source of superoxide, tyrosine nitration was substantially inhibited by urate
      formed from hypoxanthine oxidation, which was sufficient to account for the lack
      of tyrosine nitration previously reported. We conclude that peroxynitrite formed
      from the reaction of nitric oxide with superoxide at physiological pH remains an
      important species responsible for tyrosine nitration in vivo.

PMID- 10906341
TI  - Constructing side chains on near-native main chains for ab initio protein
      structure prediction.
AB  - Is there value in constructing side chains while searching protein conformational
      space during an ab initio simulation? If so, what is the most computationally
      efficient method for constructing these side chains? To answer these questions,
      four published approaches were used to construct side chain conformations on a
      range of near-native main chains generated by ab initio protein structure
      prediction methods. The accuracy of these approaches was compared with a naive
      approach that selects the most frequently observed rotamer for a given amino acid
      to construct side chains. An all-atom conditional probability discriminatory
      function is useful at selecting conformations with overall low all-atom root mean
      square deviation (r.m.s.d.) and the discrimination improves on sets that are
      closer to the native conformation. In addition, the naive approach performs as
      well as more sophisticated methods in terms of the percentage of chi(1) angles
      built accurately and the all-atom r. m.s.d., between the native and near-native
      conformations. The results suggest that the naive method would be extremely
      useful for fast and efficient side chain construction on vast numbers of
      conformations for ab initio prediction of protein structure.

PMID- 10906342
TI  - Identifying sequence-structure pairs undetected by sequence alignments.
AB  - We examine how effectively simple potential functions previously developed can
      identify compatibilities between sequences and structures of proteins for
      database searches. The potential function consists of pairwise contact energies,
      repulsive packing potentials of residues for overly dense arrangement and short
      range potentials for secondary structures, all of which were estimated from
      statistical preferences observed in known protein structures. Each potential
      energy term was modified to represent compatibilities between sequences and
      structures for globular proteins. Pairwise contact interactions in a sequence
      structure alignment are evaluated in a mean field approximation on the basis of
      probabilities of site pairs to be aligned. Gap penalties are assumed to be
      proportional to the number of contacts at each residue position, and as a result
      gaps will be more frequently placed on protein surfaces than in cores. In
      addition to minimum energy alignments, we use probability alignments made by
      successively aligning site pairs in order by pairwise alignment probabilities.
      The results show that the present energy function and alignment method can detect
      well both folds compatible with a given sequence and, inversely, sequences
      compatible with a given fold, and yield mostly similar alignments for these two
      types of sequence and structure pairs. Probability alignments consisting of most
      reliable site pairs only can yield extremely small root mean square deviations,
      and including less reliable pairs increases the deviations. Also, it is observed
      that secondary structure potentials are usefully complementary to yield improved
      alignments with this method. Remarkably, by this method some individual sequence
      structure pairs are detected having only 5-20% sequence identity.

PMID- 10906343
TI  - On the spatial disposition of the fifth transmembrane helix and the structural
      integrity of the transmembrane binding site in the opioid and ORL1 G protein
      coupled receptor family.
AB  - Evidence from statistical cluster analyses of a multiple sequence alignment of G
      protein-coupled receptor seven-helix folds supports the existence of structurally
      conserved transmembrane (TM) ligand binding sites in the opioid/opioid receptor
      like (ORL1) and amine receptor families. Based on the expectation that
      functionally conserved regions in homologous proteins will display locally higher
      levels of sequence identity compared with global sequence similarities that
      pertain to the overall fold, this approach may have wider applications in
      functional genomics to annotate sequence data. Binding sites in models of the
      kappa-opioid receptor seven-helix bundle built from the rhodopsin templates of
      Baldwin et al. (1997) [J. Mol. Biol., 272, 144-164] and Herzyk and Hubbard (1998)
      [J. Mol. Biol., 281, 742-751] are compared. The Herzyk and Hubbard template is
      found to be in better accord with experimental studies of amine, opioid and
      rhodopsin receptors owing to the reduced physical separation of the extracellular
      parts of TM helices V and VI and differences in the rotational orientation of the
      N-terminal of helix V that reveal side chain accessibilities in the Baldwin et
      al. structure to be out of phase with relative alkylation rates of engineered
      cysteine residues in the TM binding site of the alpha(2A)-adrenergic receptor. TM
      helix V in the Baldwin et al. template has been remodelled with a different
      proline kink to satisfy experimental constraints. A recent proposal that rotation
      of helix V is associated with receptor activation is critically discussed.

PMID- 10906344
TI  - Effects of pore mutations and permeant ion concentration on the spontaneous
      gating activity of OmpC porin.
AB  - Porins are trimers of beta-barrels that form channels for ions and other
      hydrophilic solutes in the outer membrane of Gram-negative bacteria. The X-ray
      structures of OmpF and PhoE show that each monomeric pore is constricted by an
      extracellular loop that folds into the channel vestibule, a motif that is highly
      conserved among bacterial porins. Electrostatic calculations have suggested that
      the distribution of ionizable groups at the constriction zone (or eyelet) may
      establish an intrinsic transverse electrostatic field across the pore, that is
      perpendicular to the pore axis. In order to study the role that electrostatic
      interactions between pore residues may have in porin function, we used
      spontaneous mutants and engineered site-directed mutants that have an altered
      charge distribution at the eyelet and compared their electrophysiological
      behavior with that of wild-type OmpC. We found that some mutations lead to
      changes in the spontaneous gating activity of OmpC porin channels. Changes in the
      concentration of permeant ions also altered this activity. These results suggest
      that the ionic interactions that exist between charged residues at the
      constriction zone of porin may play a role in the transitions between the
      channel's closed and open states.

PMID- 10906345
TI  - Thermal unfolding and conformational stability of the recombinant domain II of
      glutamate dehydrogenase from the hyperthermophile Thermotoga maritima.
AB  - Domain II (residues 189-338, M(r) = 16 222) of glutamate dehydrogenase from the
      hyperthermophilic bacterium Thermotoga maritima was used as a model system to
      study reversible unfolding thermodynamics of this hyperthermostable enzyme. The
      protein was produced in large quantities in E.COLI: using a T7 expression system.
      It was shown that the recombinant domain is monomeric in solution and that it
      comprises secondary structural elements similar to those observed in the crystal
      structure of the hexameric enzyme. The recombinant domain is thermostable and
      undergoes reversible and cooperative thermal unfolding in the pH range 5.90-8.00
      with melting temperatures between 75.1 and 68.0 degrees C. Thermal unfolding of
      the protein was studied using differential scanning calorimetry and circular
      dichroism spectroscopy. Both methods yielded comparable values. The analysis
      revealed an unfolding enthalpy at 70 degrees C of 70.2 +/- 4.0 kcal/mol and a
      DeltaC(p) value of 1.4 +/- 0.3 kcal/mol K. Chemical unfolding of the recombinant
      domain resulted in m values of 3.36 +/- 0.10 kcal/mol M for unfolding in
      guanidinium chloride and 1.46 +/- 0.04 kcal/mol M in urea. The thermodynamic
      parameters for thermal and chemical unfolding equilibria indicate that domain II
      from T.MARITIMA: glutamate dehydrogenase is a thermostable protein with a
      DeltaG(max) of 3.70 kcal/mol. However, the thermal and chemical stabilities of
      the domain are lower than those of the hexameric protein, indicating that
      interdomain interactions must play a significant role in the stabilization of T.
      MARITIMA: domain II glutamate dehydrogenase.

PMID- 10906346
TI  - Conversion of the maltogenic alpha-amylase Novamyl into a CGTase.
AB  - Novamyl is a thermostable five-domain maltogenic alpha-amylase that shows
      sequence and structural homology with the cyclodextrin glycosyltransferases
      (CGTases). Comparing X-ray crystal structures of Novamyl and CGTases, two major
      differences in the active site cleft were observed: Novamyl contains a loop
      insertion consisting of five residues (residues 191-195) and the location of an
      aromatic residue known to be essential to obtain an efficient cyclization
      reaction. To convert Novamyl into a cyclodextrin (CD)-producing enzyme, the loop
      was deleted and two substitutions, F188L and T189Y, were introduced. Unlike the
      parent Novamyl, the obtained variant is able to produce beta-CD and showed an
      overall conversion of starch to CD of 9%, compared with CGTases which are able to
      convert up to 40%. The lower conversion compared with the CGTase is probably due
      to additional differences in the active site cleft and in the starch-binding E
      domain. A variant with only the five-residue loop deleted was not able to form
      beta-CD.

PMID- 10906347
TI  - Engineering the active center of the 6-phospho-beta-galactosidase from
      Lactococcus lactis.
AB  - Several amino acids in the active center of the 6-phospho-beta-galactosidase from
      Lactococcus lactis were replaced by the corresponding residues in homologous
      enzymes of glycosidase family 1 with different specificities. Three mutants,
      W429A, K435V/Y437F and S428D/ K435V/Y437F, were constructed. W429A was found to
      have an improved specificity for glucosides compared with the wild-type,
      consistent with the theory that the amino acid at this position is relevant for
      the distinction between galactosides and glucosides. The k(cat)/K(m) for o
      nitrophenyl-beta-D-glucose-6-phosphate is 8-fold higher than for o-nitrophenyl
      beta-D-galactose-6-phosphate which is the preferred substrate of the wild-type
      enzyme. This suggests that new hydrogen bonds are formed in the mutant between
      the active site residues, presumably Gln19 or Trp421 and the C-4 hydroxyl group.
      The two other mutants with the exchanges in the phosphate-binding loop were
      tested for their ability to bind phosphorylated substrates. The triple mutant is
      inactive. The double mutant has a dramatically decreased ability to bind o
      nitrophenyl-beta-D-galactose-6-phosphate whereas the interaction with o
      nitrophenyl-beta-D-galactose is barely altered. This result shows that the 6
      phospho-beta-galactosidase and the related cyanogenic beta-glucosidase from
      Trifolium repens have different recognition mechanisms for substrates although
      the structures of the active sites are highly conserved.

PMID- 10906348
TI  - Functional expression and affinity selection of single-chain cro by phage
      display: isolation of novel DNA-binding proteins.
AB  - A robust selection system affording phage display of the DNA-binding helix-turn
      helix protein Cro is presented. The aim of the work was to construct an
      experimental system allowing for the construction and isolation of Cro-derived
      protein with new DNA-binding properties. A derivative of the phage lambda Cro
      repressor, scCro8, in which the protein subunits had been covalently connected
      via a peptide linker was expressed in fusion with the gene 3 protein of
      Escherichia coli filamentous phage. The phage-displayed single-chain Cro was
      shown to retain the DNA binding properties of its wild-type Cro counterpart
      regarding DNA sequence specificity and binding affinity. A kinetic analysis
      revealed the rate constant of dissociation of the single-chain Cro-phage/DNA
      complex to be indistinguishable from that of the free single-chain Cro. Affinity
      selection using a biotinylated DNA with a target consensus operator sequence
      allowed for a 3000-fold enrichment of phages displaying single-chain Cro over
      control phages. The selection was based on entrapment of phage/DNA complexes
      formed in solution on streptavidin-coated paramagnetic beads. The expression
      system was subsequently used to isolate variant scCro8 proteins, mutated in their
      DNA-binding residues, that specifically recognized new, unnatural target DNA
      ligands.

PMID- 10906349
TI  - Consultation-liaison cost offset: searching for the wrong grail.

PMID- 10906350
TI  - Constant observation in the general hospital.
AB  - Constant observation (CO) is a technique in which continuous one-to-one
      monitoring is used to assure the safety and well-being of an individual patient
      or others. This study reviewed 115 patient charts in a tertiary-care hospital to
      determine the correlates and predictors of the financial cost of CO. The mean
      duration for CO was 13.9 days with a median of 7.5 days. The cost average was
      $3,415 per incident with a range of $144-$68,500. The median cost was $1,872. The
      most common diagnosis was organic mental syndrome. Significant predictors of CO
      were disorientation, psychiatric medication used, and absence of alcohol use.

PMID- 10906351
TI  - Anxiety syndromes and symptoms among men with AIDS: a longitudinal controlled
      study.
AB  - This 2-year longitudinal study assessed prevalence of Axis I anxiety disorders
      and anxiety symptoms and their relationship to manifestations of HIV illness in a
      sample of nonintravenous drug users. The sample included 173 homosexual men with
      HIV or AIDS (HIV+/AIDS) and 84 homosexual men negative for HIV or AIDS (HIV-).
      Data were compared with national prevalence rates to provide a framework for
      interpretation. No significant differences were observed. However, compared with
      the general population, both HIV+/AIDS and HIV- men reported more anxiety
      symptoms and stress. For the HIV+/AIDS group there was a positive relationship
      between anxiety and HIV symptoms, fatigue, and physical limitations. No changes
      in rates or levels of anxiety were observed in those whose immunologic markers
      improved or worsened over the 2 years.

PMID- 10906352
TI  - Constant observation practices in the general hospital setting: a national
      survey.
AB  - The authors conducted a national survey of 355 general medical/surgical hospitals
      to assess constant observation (CO) practices. The authors assessed overall use,
      expense, staffing patterns, funding strategies, and cost-saving interventions.
      Virtually all responding hospitals (N = 102) reported using some form of CO.
      Several hospitals reported significant decreases in CO expenditures after the
      implementation of cost-saving interventions (the largest annual decrease reported
      was $340,000). Cost-saving interventions included utilizing consolidated bed
      spaces, relocating patients near nursing stations, placing at-risk patients in
      bed enclosure devices, and regularly assisting patients to the toilet. In
      addition, less costly personnel were hired, and volunteers and/or patient family
      members provided CO (or were required to assist with the cost of CO). Finally,
      hospital staff were educated about the costs and the appropriate use of CO. They
      were also taught to recognize and effectively treat delirium.

PMID- 10906353
TI  - Non-fearful panic disorder: a variant of panic in medical patients?
AB  - Is it possible to have panic attacks without fear? Beitman et al. reported that
      32%-41% of panic disorder (PD) patients seeking treatment for chest pain have non
      fearful panic disorder (NFPD). To replicate and extend this work on NFPD, the
      authors compared NFPD patients (N = 48), PD patients (N = 60), and No-PD patients
      (N = 333) at the time of an emergency department visit and follow-up
      approximately 2 years later. The authors compared comorbid Axis I diagnoses,
      panic attack symptoms, and scores on self-report measures. A significantly
      greater proportion of PD patients had comorbid generalized anxiety disorder and
      agoraphobia than NFPD patients. NFPD patients had self-report scores that were
      between no-PD and PD patients or similar to no-PD patients, with the exception of
      the Beck Depression Inventory. At follow-up, NFPD patients, like PD patients,
      were still symptomatic and had either not improved or had worsened according to
      scores on all self-report measures. NFPD should be recognized as a variant of PD,
      both because of its high prevalence in medical settings and its poor prognosis.

PMID- 10906354
TI  - Psychological distress among patients with musculoskeletal illness in general
      practice.
AB  - The authors investigated the importance of psychological distress and
      somatization among patients with musculoskeletal illness in general practice. The
      authors used the Hopkins Symptom Check List (SCL-8) and the Whiteley Index to
      rate 1,720 patients with musculoskeletal illness referred to physiotherapy from
      general practice. General practitioners (GPs), patients, and physiotherapists
      often noted stress or psychological distress to be a possible cause of the
      patient's musculoskeletal illness, but agreement between them was low. If the GP
      included the patient's own view on psychological distress, the result of the SCL
      8 did not add much to the detection of distress. The results emphasize the
      importance of discussing psychological distress when dealing with patients with
      musculoskeletal illness.

PMID- 10906355
TI  - European consultation-liaison services and their user populations: the European
      Consultation-Liaison Workgroup Collaborative Study.
AB  - The authors identified variations in the characteristics of patients referred to
      56 consultation-liaison (C-L) services in 11 European countries. The authors
      found differences in the types of patients referred to the services, and there
      were significant differences between countries. The first difference lays in
      whether services saw patients for deliberate self-harm and for substance abuse.
      German psychosomatic C-L services saw virtually no such patients, although in
      other C-L services these patients constituted one-quarter to one-third of the
      patients referred. The second difference lays in the remaining group of referred
      patients. This group is best characterized by two dimensions. One describes the
      severity of psychopathology -- ranging from organic mental conditions to
      somatization. The other describes the clarity of the physical diagnosis --
      ranging from patients referred by surgical wards to those referred by general
      medicine and neurology wards.

PMID- 10906357
TI  - Psychological profile and somatic complaints between help-seeking and non-help
      seeking tinnitus subjects.
AB  - In a three-group comparison, a tinnitus help-seeking group (TH) was compared on a
      number of different psychological measures with a tinnitus non-help-seeking group
      (TNH) and matched control subjects. The authors address the difference in reports
      of somatic complaints between the tinnitus help seekers and the other groups. The
      TH group showed increased scores on all psychological and somatic scales. The TNH
      group scores were more similar to those of the control subjects than the TH
      group.

PMID- 10906356
TI  - Trauma spectrum adaptation: somatic symptoms in long-term pediatric cancer
      survivors.
AB  - The authors assessed somatic symptoms and the degree of association among somatic
      symptoms, global adjustment, trauma symptoms, and personality characteristics in
      long-term pediatric cancer survivors. Forty cancer survivors completed self
      report questionnaires and clinical interviews. Participants' level of somatic
      symptoms fell between nonclinic and psychiatric populations. Somatic symptom
      scores correlated with general adjustment in the negative direction and with
      posttraumatic stress disorder (PTSD) scores in the positive direction. The
      majority of participants met at least partial current PTSD criteria. Because
      these survivors demonstrate a repressive adaptive style but endorse somatic
      symptoms, the latter may represent a method for detecting trauma-related distress
      in this population.

PMID- 10906358
TI  - Sertraline in the treatment of hiccups.

PMID- 10906359
TI  - Mirtazapine for the treatment of depression and nausea in breast and
      gynecological oncology.

PMID- 10906360
TI  - Kaposi's sarcoma: The Scarlet Letter of AIDS: the psychological effects of a skin
      disease.

PMID- 10906362
TI  - Reply to Dr. Stoudemire Reply to Dr. Stoudemire.

PMID- 10906361
TI  - Integrating medical and psychiatric treatment in an inpatient medical setting.

PMID- 10906364
TI  - In Reply.

PMID- 10906363
TI  - Diabetic ketoacidosis associated with risperidone treatment?

PMID- 10906365
TI  - Mental disorders due to a general medical condition.

PMID- 10906366
TI  - Fibromyalgia symptoms relieved by flupirtine: an open-label case series.

PMID- 10906367
TI  - Psychological factors, immunity, and heart disease.

PMID- 10906368
TI  - Insulin-resistant hyperglycemia induced by clozapine.

PMID- 10906369
TI  - Consultation-liaison psychiatry drug--drug interactions update.

PMID- 10906370
TI  - Sequence learning in Parkinson's disease: a comparison of spatial-attention and
      number-response sequences.
AB  - The serial reaction time (SRT) task has been frequently used to assess procedural
      learning of sequences. Patients with Parkinson's disease (PD) have been reported
      to show deficits on this task, but it is as yet unclear whether this impairment
      reflects a general sequencing deficit or a deficit in the sequencing of motor
      output responses. In order to examine this issue, PD patients and controls were
      administered an SRT task which allowed the simultaneous and independent
      assessment of the procedural learning of spatial regularities and the learning of
      motor-response regularities. PD patients were unimpaired at learning a sequence
      of spatial locations, but showed a deficit at learning a stimulus-to-motor
      response sequence. The results suggest that sequencing impairments in PD are not
      general, but specific to the type of sequential information inherent in a task.

PMID- 10906371
TI  - Recognition memory for emotionally negative and neutral words: an ERP study.
AB  - Scalp recorded event-related potentials were used to investigate the neural
      activity elicited by emotionally negative and emotionally neutral words during
      the performance of a recognition memory task. Behaviourally, the principal
      difference between the two word classes was that the false alarm rate for
      negative items was approximately double that for the neutral words. Correct
      recognition of neutral words was associated with three topographically distinct
      ERP memory 'old/new' effects: an early, bilateral, frontal effect which is
      hypothesised to reflect familiarity-driven recognition memory; a subsequent left
      parietally distributed effect thought to reflect recollection of the prior study
      episode; and a late onsetting, right-frontally distributed effect held to be a
      reflection of post-retrieval monitoring. The old/new effects elicited by negative
      words were qualitatively indistinguishable from those elicited by neutral items
      and, in the case of the early frontal effect, of equivalent magnitude also.
      However, the left parietal effect for negative words was smaller in magnitude and
      shorter in duration than that elicited by neutral words, whereas the right
      frontal effect was not evident in the ERPs to negative items. These differences
      between neutral and negative words in the magnitude of the left parietal and
      right frontal effects were largely attributable to the increased positivity of
      the ERPs elicited by new negative items relative to the new neutral items.
      Together, the behavioural and ERP findings add weight to the view that
      emotionally valenced words influence recognition memory primarily by virtue of
      their high levels of 'semantic cohesion', which leads to a tendency for 'false
      recollection' of unstudied items.

PMID- 10906372
TI  - Why are some patients with severe neglect able to copy a cube? The significance
      of verbal intelligence.
AB  - Cube-copying is often used to assess constructional ability of brain-damaged
      patients and the influence of unilateral spatial neglect is often pointed out in
      patients with right hemisphere lesions. However, some patients with severe
      neglect perform cube-copying satisfactorily. The aim of the present study is to
      identify the factors that affect the performance of cube-copying in patients with
      left unilateral spatial neglect. Constructional performance was investigated in
      100 patients with unilateral spatial neglect using a task to copy the Necker
      cube. The relationship of the patients' cube-copying performance to the severity
      of their neglect, as well as other factors (verbal intelligence, age, duration
      after onset of the disease, educational level, lesion site, piecemeal approach,
      and side of starting to copy) was analyzed. Twenty-two normal subjects also
      participated in this study as controls. Among many factors adopted for analysis,
      neglect severity and verbal intelligence were found to be primary factors
      affecting the cube-copying performance of the patients with unilateral spatial
      neglect. The effect of neglect severity on cube-copying performance was apparent
      in the patients whose verbal intelligence was deteriorated, but was not observed
      in the patients with preserved verbal intelligence. Similarly, the effect of
      verbal intelligence on cube-copying performance was apparent in the patients with
      severe neglect, but not in the patients with mild neglect. We conclude that
      constructional ability in the copying of a cube is determined by verbal
      intelligence, as well as by the severity of unilateral spatial neglect.

PMID- 10906373
TI  - Binocular cues are important in controlling the grasp but not the reach in
      natural prehension movements.
AB  - Binocular cues are typically considered to be pre-eminent in the control of
      reaching and grasping behaviour. However, in the absence of such information
      prehension movements can still be accurate and reliable. The present study
      therefore was designed to assess further the contribution of binocular
      information in the control of human reaching and grasping movements. Participants
      reached for and picked up objects under binocular and monocular viewing, both in
      the absence of a visible scene around the target objects (complete darkness with
      'self-illuminated' objects and hand), and under normal (fully illuminated)
      viewing. Analysis of kinematic parameters indicated that the removal of binocular
      information did not significantly affect the major indices of the transport
      component, although it did affect the grasp component. In contrast, the kinematic
      parameters in the unlit conditions revealed that both the transport component and
      the grasp component of the reach were severely disrupted whether binocular cues
      were available or not. Our results suggest that binocular information may be more
      important for the control of grasp formation than for the control of the
      transport component. Elimination of the surrounding scene and normal visual
      feedback affects both the transport and the grasp. It is concluded that in normal
      viewing conditions, reaching and grasping movements are less dependent on
      binocular information than has previously been thought.

PMID- 10906374
TI  - Event-related potentials during auditory language processing in congenitally
      blind and sighted people.
AB  - While behavioral studies have documented delayed language acquisition in blind
      children, other studies have revealed better speech discrimination abilities for
      blind than sighted adults. Several brain imaging studies have provided evidence
      for cortical reorganization due to visual deprivation but the cerebral
      organization of language in blind humans is not known yet. We hypothesized that
      the increasing specialization of language systems normally observed during
      development may not take place to the same degree in blind individuals since
      posterior visual areas do not receive their adequate input. On the other hand, we
      hypothesized that blind people, due to their greater reliance upon the auditory
      language signal, may process speech faster than sighted people. To test these
      assumptions, event-related potentials were recorded while 11 congenitally blind
      and 11 sighted adults matched in age, gender, handedness and education were
      engaged in a language task. Participants listened to sentences in order to decide
      after each sentence if it was meaningful or not. Incongruous sentence-final words
      elicited an N400 effect in both groups. The N400 effect had a left-lateralized
      fronto-central scalp distribution in the sighted but a symmetric and broad
      topography in the blind. Furthermore, the N400 effect started earlier in the
      blind than in the sighted. Closed class compared to open class sentence middle
      words elicited a more pronounced late negativity in the blind than in the
      sighted. These results suggest that blind people process auditory language
      stimuli faster than sighted people and that some language functions may be
      reorganized in the blind.

PMID- 10906375
TI  - Organization of working memory within the human prefrontal cortex: a PET study of
      self-ordered object working memory.
AB  - The prefrontal cortex plays a critical role in working memory, the active
      maintenance of information for brief periods of time for guiding future motor and
      cognitive processes. Two competing models have emerged to account for the growing
      human and non-human primate literature examining the functional neuroanatomy of
      working memory. One theory holds that the lateral frontal cortex plays a domain
      specific role in working memory with the dorsolateral and ventrolateral cortical
      regions supporting working memory for spatial and non-spatial material,
      respectively. Alternatively, the lateral frontal cortex may play a process
      specific role with the more dorsal regions becoming recruited whenever active
      manipulation or monitoring of information in working memory becomes necessary.
      Many working memory tasks do not allow for direct tests of these competing
      models. The present study used a novel self-ordered working memory task and
      positron emission tomography to identify whether dorsal or ventral lateral
      cortical areas are recruited during a working memory task that required extensive
      monitoring of non-spatial information held within working memory. We observed
      increased blood flow in the right dorsolateral, but not ventrolateral, prefrontal
      cortex. Increases in blood flow in the dorsolateral region correlated strongly
      with task performance. Thus, the results support the process-specific hypothesis.

PMID- 10906377
TI  - ERP effects of listening to speech: semantic ERP effects.
AB  - In this study, event-related brain potential effects of speech processing are
      obtained and compared to similar effects in sentence reading. In two experiments
      spoken sentences were presented with semantic violations in sentence-final or mid
      sentence positions. For these violations N400 effects were obtained that were
      very similar to N400 effects obtained in reading. However, the N400 effects in
      speech were preceded by an earlier negativity (N250). This negativity is not
      commonly observed with written input. The early effect is explained as a
      manifestation of a mismatch between the word forms expected on the basis of the
      context, and the actual cohort of activated word candidates that is generated on
      the basis of the speech signal.

PMID- 10906376
TI  - A comparative study of aimed throwing by monkeys and humans.
AB  - This research examined hand preference and postural characteristics of aimed
      throwing in capuchin monkeys and humans. We sought to directly compare the
      throwing performances of these primates, particularly the extent to which target
      distance influences hand preference, throwing posture, and throwing accuracy. For
      both species we found positive correlations between target distances for throwing
      accuracy, direction and strength of hand preference, percentage of bipedal vs
      tripedal throws, and percentage of overarm vs underarm throws. Throwing accuracy
      did not vary as a function of right vs left hand use although for monkeys
      throwing accuracy was positively associated with hand preference strength. We
      noted a sex difference among humans as males threw more accurately than did
      females. Between-species analysis indicated that humans exhibited greater right-
      vs left-hand use, greater hand preference strength, a greater relative percentage
      of bipedal vs tripedal throws, and a lower relative percentage of overarm vs
      underarm throws than did monkeys. We believe that the capuchin monkey is an
      informative nonhuman primate model of aimed throwing in humans and that research
      examining the throwing behavior of capuchins provides insight into the
      neurological and behavioral characteristics that underlie coordinated multi-joint
      movements across the primate order.

PMID- 10906378
TI  - ERP effects of listening to speech compared to reading: the P600/SPS to syntactic
      violations in spoken sentences and rapid serial visual presentation.
AB  - In this study, event-related brain potential effects of speech processing are
      obtained and compared to similar effects in sentence reading. In two experiments
      sentences were presented that contained three different types of grammatical
      violations. In one experiment sentences were presented word by word at a rate of
      four words per second. The grammatical violations elicited a Syntactic Positive
      Shift (P600/SPS), 500 ms after the onset of the word that rendered the sentence
      ungrammatical. The P600/SPS consisted of two phases, an early phase with a
      relatively equal anterior-posterior distribution and a later phase with a strong
      posterior distribution. We interpret the first phase as an indication of
      structural integration complexity, and the second phase as an indication of
      failing parsing operations and/or an attempt at reanalysis. In the second
      experiment the same syntactic violations were presented in sentences spoken at a
      normal rate and with normal intonation. These violations elicited a P600/SPS with
      the same onset as was observed for the reading of these sentences. In addition
      two of the three violations showed a preceding frontal negativity, most clearly
      over the left hemisphere.

PMID- 10906379
TI  - Laser eye injuries.
AB  - Laser instruments are used in many spheres of human activity, including medicine,
      industry, laboratory research, entertainment, and, notably, the military. This
      widespread use of lasers has resulted in many accidental injuries. Injuries are
      almost always retinal, because of the concentration of visible and near-infrared
      radiation on the retina. The retina is therefore the body tissue most vulnerable
      to laser radiation. The nature and severity of this type of retinal injury is
      determined by multiple laser-related and eye-related factors, the most important
      being the duration and amount of energy delivered and the retinal location of the
      lesion. The clinical course of significant retinal laser injuries is
      characterized by sudden loss of vision, often followed by marked improvement over
      a few weeks, and occasionally severe late complications. Medical and surgical
      treatment is limited. Laser devices hazardous to the human eye are currently in
      widespread use by armed forces. Furthermore, lasers may be employed specifically
      for visual incapacitation on future battlefields. Adherence to safety practices
      effectively prevents accidental laser-induced ocular injuries. However, there is
      no practical way to prevent injuries that are maliciously inflicted, as expected
      from laser weapons.

PMID- 10906380
TI  - Abnormal supranuclear eye movements in the child: a practical guide to
      examination and interpretation.
AB  - Abnormal eye movements in the infant or voting child can be congenital or
      acquired. They may be a result of abnormal early visual development or a sign of
      underlying neurologic or neuromuscular disease. It is important to be able to
      detect these abnormalities and to distinguish them from normal but immature eye
      movements. The spectrum of disease in children differs from that in adults.
      Serious, potentially fatal but treatable disorders can be acquired in infancy,
      and abnormal eye movements in a sometimes apparently well child should never be
      labeled as congenital or benign without careful investigation. Eye movement
      analysis can indicate the presence of an underlying condition and help the
      clinician to classify different neurologic diseases. It is important to carefully
      examine the ocular motor system in any children at risk of neurologic disease.
      This review provides a practical guide to the examination and interpretation of
      eye movements in the child and includes recent literature on eye movement
      disorders of childhood. We describe supranuclear abnormalities of the ocular
      motor system in the order in which we would normally examine it: saccades,
      pursuit, convergence, vestibulo-ocular reflex, and optokinetic nystagmus.
      Nystagmus, internuclear ophthalmoplegia, cranial nerve abnormalities, and
      "miswiring" phenomena (such as Duane's syndrome and synergistic divergence) are
      not discussed.

PMID- 10906381
TI  - Visual loss in a 42-year-old man.
AB  - A 42-year-old man developed blurred vision and was found to have a right,
      incongruous, inferior homonymous quadrantanopia. Neuroimaging disclosed a
      suprasellar mass. The mass was thought to be a pituitary adenoma that was
      compressing the left optic tract, and transsphenoidal surgery was planned;
      however, because the defect was primarily inferior, indicating damage to the
      superior aspect of the optic tract, it was recommended that a craniotomy be
      performed. The mass was found at surgery to be a craniopharyngioma.

PMID- 10906382
TI  - Acute bilateral ophthalmoplegia in a young woman.
AB  - A 34-year-old woman presented with bilateral ophthalmoplegia, ptosis, and mild
      gait ataxia. Tensilon test, magnetic resonance imaging, and cerebrospinal fluid
      analysis were normal. She initially denied any alcohol intake but later admitted
      to significant alcohol and multisubstance abuse. The patient improved
      dramatically after treatment with thiamine. Wernicke's encephalopathy is
      discussed, highlighting that it may be present with normal mentation. It should
      be considered in the differential diagnosis of bilateral ophthalmoplegia even in
      the absence of altered mental status.

PMID- 10906383
TI  - Iris involvement in primary intraocular lymphoma: report of two cases and review
      of the literature.
AB  - Non-Hodgkin's lymphoma involves ocular tissues either as a primary tumor or as
      secondary metastasis from systemic disease. Diagnosis is based on the
      identification of malignant cells in the eye by biopsy. Although primary
      intraocular lymphoma cells have been identified in the optic nerve, ciliary body,
      and iris of a small number of patients by histopathology, these sites of
      infiltration have rarely been observed on clinical examination. We studied
      clinical and histopathological findings of two patients with iris infiltration by
      primary intraocular lymphoma and reviewed the findings of 163 cases reported in
      the literature.

PMID- 10906384
TI  - "Glaucoma affecting each crystalline lens": a long-lost manuscript by Dr. William
      Mackenzie.
AB  - Dr. William Mackenzie was one of the great pioneers of British ophthalmology in
      the 19th century. We present a newly-discovered manuscript in which Mackenzie
      described how he performed surgery for bilateral nuclear sclerosis of the lens,
      in 1842-1843. This case became the focus for a discussion of the nature of
      "cataract" and "glaucoma" in the fourth edition of Mackenzie's great work, A
      practical treatise on diseases of the eye. Mackenzie is generally remembered as a
      great compiler of knowledge, but the text Mackenzie built around this case shows
      him pursuing original arguments based on his own observation. This case report
      gives us a vignette of Mackenzie that illustrates aspects of Mackenzie's
      character and achievements in an intimate way, and it dramatizes in a lively
      manner how some of the most fundamental concepts in ophthalmology evolved.

PMID- 10906385
TI  - Cloning of the first invertebrate MAGE paralogue: an epitope that activates T
      cells in humans is highly conserved in evolution.
AB  - The MAGE (Melanoma Associated Antigen) family tumor-specific antigens are shared
      by a number of histologically different tumors. Till date, only human and mouse
      MAGE genes have been characterized. Our study describes the first non-mammalian
      member of MAGE super-family, DMAGE from D. melanogaster. A conceptual translation
      of the cDNA of DMAGE identifies a putative protein that contains a motif that
      shares eight out of nine amino acids with the previously identified promiscuous,
      HLA-A2 restricted antigenic epitope in the C-terminus of human MAGE-B1 and -B2.
      Similarly, this motif of DMAGE shares seven out of nine amino acids with the same
      antigenic epitope of human MAGE-A3 and -A12. Thus, the phylogeny of proteins that
      activate tumor specific T-cells in mammals as unmutated self-proteins began at
      least 100 million years earlier in evolution than the emergence of the adaptive
      immune system of higher vertebrates. Northern analysis revealed that DMAGE is a
      developmentally regulated gene highly expressed in adult fruit fly and in the
      embryo of D. melanogaster. In contrast, the expression level of the mRNA of DMAGE
      in fruit fly larva is substantially lower than in embryo and adult fly. We
      propose that studies of DMAGE on D. melanogaster may help define the function(s)
      of MAGE super-family genes.

PMID- 10906386
TI  - The onset of phagocytosis and identity in the embryo of Lytechinus variegatus.
AB  - The stage at which phagocytosis can first be characterized in the embryos of the
      sea urchin Lytechinus variegatus was investigated by microinjecting the yeast
      Saccharomyces cerevisiae into its blastocoele. Secondary mesenchyme cells were
      first observed phagocytosing during the mid-gastrula stage. Subsequently, as the
      incubation time increased, the number of yeast per phagocyte rose. Using vital
      fluorescence dyes, stained free yeast were seen in the blastocoele during late
      gastrula stage, indicating cell death and suggesting specific factors, such as
      proteases, in the extracellular environment. The starting point of phagocytic
      activity reflects a biological capacity for distinguishing between self and
      nonself. Thus, the phagocytosis of yeast by mesenchymal cells beginning in the
      mid-gastrula stage in L. variegatus may indicate the moment of acquisition of
      'identity' (self) in this organism. Comparative aspects of embryo and adult
      phagocytes in L. variegatus are also discussed.

PMID- 10906388
TI  - The major histocompatibility class II alpha chain in salmonid fishes.
AB  - In this study the characterisation of the Atlantic salmon (MhcSasa-DAA) and
      rainbow trout (MhcOnmy-DAA) class II alpha chain cDNA sequences is presented. The
      DAA sequences from these two salmonid species showed a high degree of similarity,
      although the Onmy-DAA(*)03 cDNA sequence differed in the cytoplasmic region.
      Interestingly, the Onmy-DAA(*)02 sequence has lost the second cysteine in the
      alpha-1 domain. However, another cysteine is present in this sequence 7 positions
      downstream of the cysteine which is substituted for a leucine. Despite a thorough
      search, only a single locus of expressed class II alpha chain sequences was
      identified in both salmonid species. Amplification by PCR and sequencing of the
      alpha-1 domain from genomic DNA of three Atlantic salmon, identified four
      different variants assumed to have derived from this single locus. Two of these
      variants originated from one individual and are likely functional alleles.

PMID- 10906387
TI  - Characterization and expression of an EB1 protein in Ictalurus punctatus
      neutrophils.
AB  - We have identified an EB1 gene (CfEB1) and protein in channel catfish
      neutrophils. The complete cDNA sequence is 1725 bp and the putative protein is
      composed of 258 amino acids. Western blot analysis of channel catfish neutrophil
      cell membrane with a monoclonal antibody (14I) yielded a 28 kD protein band with
      the protein preparation. Aside from neutrophils only a small percentage of other
      cells tested expressed detectable amounts of EB1 as determined by flow cytometry.
      Furthermore, EB1 expression increased after phorbol dibutyrate stimulation of
      neutrophils or incubation of catfish neutrophils with Edwardsiella ictaluri.
      Nonpermeabilized, fixed catfish neutrophils demonstrated immunofluorescent
      staining with 14I indicating that EB1 is apparently externally oriented in
      catfish neutrophils. This is the first report of the external orientation of the
      EB1 molecule. Because of its increase after stimulation and detection on cell
      membranes, EB1 may participate in catfish neutrophil cell regulation, signal
      transduction, or cell membrane changes necessary for phagocytosis.

PMID- 10906389
TI  - Cloning of a CXCR4 homolog in chondrostean fish and characterization of the CXCR4
      specific structural features.
AB  - The chemokine receptor CXCR4 and its ligand SDF-1 are essential components of
      hematopoiesis, organogenesis and immunomodulation in mammalian species. We cloned
      a cDNA encoding CXCR4 homolog of sterlet (Acipenser ruthenus), a representative
      of chondrostean fishes. The deduced amino acid sequence of sterlet CXCR4 is
      almost equally distant from mammalian and teleost CXCR4 (66-68% identical
      residues). Percent identity with the other chemokine receptors varies in the 30
      35% range. The CXCR4 sequences from the three phylogenetically diverged lineages
      were compared with the sequences of the other chemokine receptors to determine
      the CXCR4-specific structural elements that were conserved during vertebrate
      evolution. The characteristic residues and/or motifs are located predominantly in
      the intracellular and extracellular regions and in the third, fourth and fifth
      transmembrane domains. The data presented may be helpful for structure-function
      analysis of the CXCR4 ligand binding and signal transduction.

PMID- 10906391
TI  - Altered development of intestinal intraepithelial lymphocytes in P-glycoprotein
      deficient mice.
AB  - Intraepithelial lymphocytes (IEL) that reside in the intestinal epithelium are
      known to exhibit phenotypic and functional characteristics that are distinct from
      other T cells. We have recently shown that peripheral T cells exclusively express
      an isoform of P-glycoprotein (P-gp) encoded by the mdr1a gene, but do not require
      mdr1a expression for normal proliferative, cytokine, or cytotoxic responses. In
      the present study, we have used mdr1-type knockout (KO) mice to demonstrate that
      IEL also utilize mdr1a, but only preferentially, in that the mdr1b isoform can be
      expressed in the absence of mdr1a expression. We also report that a high level of
      P-gp activity appears to be necessary for the normal development of certain IEL
      subpopulations. In specific, while the total number of IEL was relatively
      unaffected by the absence of mdr1a expression, the proportions of CD8 alpha beta
      and TCR alpha beta+ IEL increased significantly in mdr1a and mdr1a/b KO mice at
      the expense of CD8 alpha alpha and TCR gamma delta+ IEL, respectively. Moreover,
      these subset alterations also appeared to have functional consequences, in that
      proliferative, IL-2, and IFN-gamma responses of IEL from KO mice were distinct
      from those of normal IEL. In summary, our data suggest that mdr1a expression is
      required for the development of certain IEL subpopulations, most notably TCR
      gamma delta+ cells, and thereby indirectly influences the balance of T cell
      subsets in the intestinal epithelium.

PMID- 10906390
TI  - Immune system cell markers in the northern brown bandicoot, Isoodon macrourus.
AB  - This is the first study to report the presence of T and B lymphocyte markers and
      antigen presenting-like molecules in a marsupial bandicoot. Intra-cytoplasmic
      markers for CD3 and CD5, as well as surface Thy-1.1 and CD1a molecules were
      located in lymphocytes of T dependent regions of immuno-lymphoid tissue in the
      northern brown bandicoot using immunohistochemical techniques. Similarly, intra
      cytoplasmic domains of CD79a, CD79b molecules and surface IgG molecules enabled
      characterisation of B lymphocytes and plasma cells. The phenotypic expression of
      these molecules parallels findings in eutherians, suggesting firstly the
      conservation of lineage epitopes for T and B subsets and secondly, the potential
      for similar functional properties of immune system cells between marsupials and
      eutherians. In addition, the presence of MHC class II and CD1a molecules on
      dendritic-like cells may indicate similar mechanisms for antigen processing and
      presentation as reported in eutherians. The use of such immune system cell
      markers will enable functional studies to characterise the marsupial immune
      system as well as ontogeny studies of immune competence.

PMID- 10906392
TI  - A morphological and immunohistological study of the human and rabbit appendix for
      comparison with the avian bursa.
AB  - Diversification of the primary antibody repertoire occurs in young rabbit
      appendix. As a prelude to molecular investigation of whether human appendix has a
      similar role, we compared the lymphoid morphology and distribution of common B-
      and T-cell subsets in frozen and/or paraffin-embedded normal appendix specimens
      at various ages. IgA, IgM and IgG staining patterns were similar in frozen human
      and rabbit appendices. The elongated follicles of the young human and rabbit
      appendices regressed with age to resemble Peyer's patches. Although similar in
      morphology to the bursa, human and rabbit appendix follicles differ in that they
      do not involute completely with age and contain significant numbers of germinal
      center (GC) T cells although the number is low early in life. If the human
      appendix functions as a primary lymphoid organ, it may occur during the first few
      months of age when the GC T-cell density is low.

PMID- 10906394
TI  - Aversion learning techniques to evaluate dairy cattle handling practices.
AB  - Fear of humans is a source of stress for Holstein dairy cattle and can result
      when animals are handled aversively. We used aversion learning techniques to
      determine which handling practices cattle find most aversive. In an aversion
      race, the cows are repeatedly walked down a race and treatments applied when they
      reached the end; the time and force required for cows to walk down the race are
      measured. The animal learns to associate walking down the race with the treatment
      received; if the treatment is aversive, the animal will take more time and
      require more force to reach the end of the race than if the treatment is
      positive. In experiment 1, 54 cows were assigned to four treatments (hit/shout,
      brushing, control, and food). Treatments of 2-min duration were applied three
      times a day for 4 days. Cows on the hit/shout treatment took more time and
      required more force to walk through the race than cows on other treatments, while
      brushed cows took longer to move through the race than cows given food. In
      experiment 2, 60 cows were assigned to five treatments (electric prod, shouting,
      hitting, tail twist, and control). Treatments of 1-min duration were applied
      three times a day for 3 days. Cows on the shout and electric prod treatments took
      more time and required more force to walk down the race than cows on the control
      treatment. In experiment 3, thirty-six 1-1.5-year-old heifers were assigned to
      three treatments (hand feeding, gentling, or control) applied as in experiment 2.
      Treatments did not affect the time or force required to walk down the race. The
      aversion race successfully discriminated between handling treatments that differ
      greatly in aversiveness but lacked sensitivity to distinguish between treatments
      that were similar. Although many procedural factors must be considered, aversion
      learning techniques are an effective method to determine which handling practices
      cattle find aversive or rewarding.

PMID- 10906395
TI  - The effect of irregular feeding times on the behaviour and growth of dairy
      calves.
AB  - The objective of this study was to examine the effects of predictable vs.
      unpredictable management routines on the behaviour, production and health of
      dairy calves. Three different feeding schedules for milk-fed dairy calves were
      compared. All calves received milk twice a day, and had free access to
      concentrate, hay and water. Three groups of 12 calves (divided on two trials)
      were exposed to one of the following treatments from the age of 5 days to 9
      weeks: group C (control) received milk at the same time every day, at 0700 and
      1400. Group OD (occasional deviation) received the milk at the same time every
      day except on treatment days, one in week 5 and one in week 8, where they were
      fed 3 h later. Group IR (irregular schedule) received milk at irregular times
      throughout the experimental period. The first daily feeding took place between
      0600 and 1300 and the second one between 1300 and 2100. When the calves were 5
      and 8 weeks old, the behaviour of eight calves from each group was videorecorded
      for two days (48 h). The following behaviour was recorded: frequency and duration
      of lying bouts and frequency of comfort behaviour (defined as licking or
      scratching own body), eating, drinking, other oral behaviour and extending the
      head through the feeding barrier (HTB). The milk and concentrate consumption of
      the calves was measured and the calves were weighed weekly. Diseases were
      recorded.The results showed that at the age of 5 weeks, the calves in group IR
      differed from the control group C by performing more eating behaviour both on the
      control day (27.5 vs. 15.5; p<0.05) and the treatment day (28.8 vs. 18.3;
      p<0.05). At the age of 8 weeks, no differences were found in the behaviour
      between groups IR and C. When the OD calves were 5 weeks old, they responded to
      the delayed feeding by increasing drinking behaviour (14.5 vs. 9.0; p<0.05). When
      they were 8 weeks old, they showed increased frequency of comfort (195 vs. 122;
      p<.05), eating (37.5 vs. 27.9; p<0.05) and HTB behaviour (19.8 vs. 7.4; p<0.001)
      on the treatment day compared to the control day. The IR group did not respond to
      the same treatment except for a slight increase in drinking behaviour (9.6 vs.
      6.5; p<0.05) at the age of 8 weeks. No differences were observed in the frequency
      or length of lying bouts, nor health or production parameters between the three
      groups.It is concluded that a predictable feeding schedule may not be very
      important for milk-fed dairy calves. However, when the calves are customised to
      predictable feeding times, occasional deviations from that schedule may cause
      frustration when their expectations are not fulfilled.

PMID- 10906393
TI  - Conservation in decay accelerating factor (DAF) structure among primates.
AB  - The decay accelerating factor (DAF, CD55) protects self cells from activation of
      autologous complement on their surfaces. It functions to disable the C3
      convertases, the central amplification enzymes of the cascade. Its active site(s)
      are contained within four approximately 60 amino acid long units, termed
      complement control protein repeats (CCPs), which are suspended above the cell
      surface on a 68 amino acid long serine/threonine (S/T)-rich cushion that derives
      from three exons. We previously proposed a molecular model of human DAF's four
      CCPs in which certain amino acids were postulated to be recognition sites for the
      interaction between DAF and the C3 convertases. In the current study, we
      characterized DAF in five non-human primates: the great apes, gorilla and common
      chimpanzee, and the Old World monkeys: hamadryas baboon, Rhesus macaque, and
      patas monkey. Amino acid homology to human DAF was approximately 98% for the two
      great apes and 83% for the three Old World monkeys. The above cited putative
      ligand interactive residues were found to be fully conserved in all of the non
      human primates, although there were amino acid changes outside of these areas. In
      the chimpanzee, alternative splicing of the S/T region was found potentially to
      be the source of multiple protein isoforms in erythrocytes, whereas in the patas
      monkey, similar alternative splicing was observed but only one protein band was
      seen. Interestingly, a Rhesus macaque was found to exhibit a phenomenon
      paralleling the human Cromer Dr(a-) blood group, in which a 44-base pair deletion
      in CCP3 leads to a frameshift and early STOP codon.

PMID- 10906396
TI  - The effects of branches on prepartum nest building in gilts with access to straw.
AB  - Sows farrowing in a semi-natural environment terminate nest building 1-7 h prior
      to parturition after having built a nest for which a variety of materials are
      used. No nest-building behaviour occurs during parturition and the sows remain
      lying in the nest throughout most of the farrowing. In contrast, many intensively
      housed sows are restless during farrowing. To investigate whether gilts housed
      indoors would use branches for nest building and whether access to branches would
      affect the termination of nest building and parturient behaviour, we studied
      gilts housed individually in pens designed to stimulate natural nest building.
      The control group (n=21) had unlimited access to straw and the experimental group
      (n=21) had unlimited access to straw and branches. During nest building all the
      gilts used straw and all the experimental gilts also used branches. In the
      experimental group the interval from termination of nest building to birth of the
      first piglet (BFP) was significantly longer than in the control group (132 versus
      58 min, P=0.04). In the experimental group, nest-building behaviour was also
      performed by fewer individuals during the interval from BFP until 2 h after than
      in the control group (38% versus 71% of the gilts, P=0.03). Gilts that performed
      nest building during this interval carried out more postural changes (P<0.001)
      and spent less time in lateral recumbency (P=0.001) than gilts which did not
      perform nest building. On average, gilts that performed nest building behaviour
      after BFP (n=26) spent 54% of the first 2 h of parturition in lateral recumbency
      and carried out 16 postural changes. Gilts that did not perform nest building
      behaviour during this interval (n=16) spent 85% of the time in lateral recumbency
      and carried out five postural changes. In 10 gilts that were selected randomly
      from the experimental group nest building was studied in more detail. In these
      gilts nest building peaked between 17 and 6 h prepartum. There was no difference
      in amount of behaviour directed towards straw and amount of behaviour directed
      towards branches.The results indicate that the termination of nest building in
      sows is under environmental feedback control. When only straw was provided the
      nests did not have much of a lasting structure. However, when gilts had access to
      straw and branches more structured and functional nests could be built. These
      nests may have been more effective in reducing the motivation for nest building
      prior to the onset of parturition.

PMID- 10906397
TI  - Ease of capture in lines of Japanese quail (Coturnix japonica) subjected to
      contrasting selection for fear or sociability.
AB  - Japanese quail (Coturnix japonica) of lines, which have been subjected to
      contrasting selection for duration of the tonic immobility (TI) reaction or
      social reinstatement (SR) behaviour over many generations show corresponding
      differences in underlying fearfulness and sociality. As fearfulness and sociality
      are particularly influential traits in domesticated species, the finding that
      such traits respond to artificial selection may have important implications for
      poultry welfare and performance. However, it is not known if or how such
      selection has influenced human-animal interactions. The present experiment
      investigated the influence of fearfulness and SR behaviour on the ease with which
      birds could be caught and handled. Birds of lines selected for duration of the TI
      response or SR behaviour were reared in mixed line groups (LTI and STI or HSR and
      LSR) of 491 and 346 birds, respectively, until 6 weeks of age. When the birds
      were 2, 4, and 6 weeks of age, they were caught one by one and their individual
      capture ranks noted. In the group of birds selected for duration of the TI
      response, birds selected of the line selected for short duration of TI were
      caught before those selected for long duration of the response. In the group of
      birds selected for SR motivation, birds of the high line were caught before their
      low lines counterparts. Coefficients of concordance between capture ranks were
      significant and capture ranks did not differ significantly across ages. These
      results imply that selection for low levels of fear or high levels of sociality
      produces animals that are less disturbed by human interventions than animals
      selected for the opposite traits. The greater ease of capture of low fear line
      birds than high fear line birds may be explained by reduced fear of humans. The
      fact that the birds selected for high levels of SR behaviour are easier to catch
      than birds selected for low levels of sociality is less readily explicable. One
      hypothesis is that HSR line chicks tend to be more strongly imprinted on each
      other and the human caretaker. However, SR behaviour is highly species specific
      in both lines, existing evidence for line differences in social discrimination is
      limited and birds of the two lines show similar duration of the TI response.
      Despite this, whatever their underlying causation, these results demonstrate that
      genetic selection can be used to reduce negative reactions to human beings and
      may be of value in the improvement of both animal welfare and productivity.

PMID- 10906398
TI  - Effects of qualitative and quantitative food restriction treatments on feeding
      motivational state and general activity level of growing broiler breeders.
AB  - Growing broiler breeder chickens are fed restricted rations to limit body weight
      at sexual maturity. This experiment tested a proposal (Brouns, F., Edwards, S.A.,
      English, P.R., 1994. Effect of dietary fibre and feeding system on activity and
      oral behaviour of group housed gilts. Appl. Anim. Behav. Sci. 39, 215-223.) that
      feeding motivation is reduced by using qualitative rather than quantitative food
      restriction, and it examined relationships among suppression of growth rate,
      feeding motivational state and general activity level. From 2 to 15 weeks of age,
      female broiler breeders were reared in six groups of 20, each with a different
      feeding treatment. The six treatments were: high and low levels of diet dilution
      (600-700 g/kg and 300-350 g/kg oat feed, ad libitum), appetite suppression (50-60
      g/kg and 25-30 g/kg calcium propionate, ad libitum) and quantitative restriction
      (recommended daily ration and twice that amount). Birds were conditioned to an
      operant (PR1 schedule) feeding procedure with their respective treatment diets
      from 3 to 7 weeks, and this was used to measure feeding motivation in 12-min
      tests at three times of day (1000, 1300 and 1600 h) at 8, 10, 12 and 14 weeks.
      Proportions of time spent sitting were measured as an index of general inactivity
      in systematic observations at 9, 11, 13 and 15 weeks. Although the diet dilution
      and appetite suppression (qualitative) treatments did not limit growth rates as
      intended, they and the quantitative treatments produced a range of mean body
      weights to compare with feeding motivation whenever birds were tested. With body
      weight as a covariate, there were significant effects on numbers of operant
      responses in 12 min (the measure of feeding motivation) of weight, age, time of
      day and treatmentxtime interaction, but not treatment. Feeding motivation was
      positively correlated with suppression of growth rate, regardless of how that
      suppression was achieved. However, the experimental procedure required all test
      birds to be without food from 0900 or 0915 h, and motivation was lowest in the
      earliest (1000 h) test with qualitative but not quantitative treatments. Hence,
      there was some evidence that feeding motivation may be partially suppressed with
      qualitative food restriction; distinction can be made between short-term and
      longer-term feeding motivation. General activity level (inversely reflected by
      time spent sitting) was closely correlated positively with both suppression of
      growth rate and feeding motivation. As a fundamental relationship between feeding
      motivation and reduction of growth rate was not altered by using qualitative
      rather than quantitative food restriction, these results support an earlier
      conclusion (Savory, C.J., Hocking, P.M., Mann, J.S., Maxwell, M.H., 1996. Is
      broiler breeder welfare improved by using qualitative rather than quantitative
      food restriction to limit growth rate? Anim. Welfare 5, 105-127.) that broiler
      breeder welfare is not improved with qualitative restriction methods.

PMID- 10906399
TI  - Taste reactivity patterns in domestic cats (Felis silvestris catus).
AB  - The present study is aimed at finding taste reactivity patterns in domestic cats
      (Felis silvestris catus) which reflect 'liking' or perceived palatability. Three
      groups of nonstressed cats living in households were formed which a priori were
      expected to differ in motivational state for eating food items (more or less
      hungry), and which were offered two different food items differing in general
      taste properties (more or less flavourful food, MFF and LFF, respectively) around
      the time that they were fed their normal food. Analysis of the amount of food
      eaten showed that MFF was consumed regardless of hunger level and that LFF was
      consumed depending on the hunger level of cats: the more hungry cats ate more of
      LFF than the less hungry cats. Analysis of post-meal behavioural sequences showed
      that the 'MFF consumption sequence' differed from the 'LFF refusal sequence' and
      that the 'LFF consumption sequence' strongly resembled the 'MFF consumption
      sequence' but also contained elements of the 'LFF refusal sequence'. Subsequent
      analysis of the frequencies and total durations of behavioural patterns showed
      that two kinds of patterns existed, possibly reflecting two 'palatability
      dimensions': hedonic taste reactivity patterns (lick/sniff feeding bowl, lip lick
      and groom face) and aversive taste reactivity patterns (lick/sniff food and lick
      nose). These dimensions may be combined to obtain a single palatability score.

PMID- 10906400
TI  - No effect of variation in handling on behaviour in a porcine elevated plus-maze -
      a brief report.
AB  - The elevated plus-maze is a widely used model of anxiety in rodents and has
      recently been suggested as a putative model of anxiety or fear in swine. The aim
      of the present experiment was to examine the effects of a pretest blood sampling
      procedure on the behaviour of weaned pigs in an elevated plus-maze. Animals in
      the control group were lifted one-by-one into a transport trolley and moved to
      the test apparatus, where they were observed for a 5-min period. The treatment
      group differed from the control group in that these animals were immobilized with
      a nose snare and a blood sample was extracted from the jugular vein prior to
      transport to the test room. Behaviour in the porcine elevated plus-maze did not
      differ significantly between the two handling procedures.

PMID- 10906401
TI  - Erratum to "Cereal aversion in behaviourally resistant house mice in Birmingham,
      UK"

PMID- 10906402
TI  - Effects of early separation on the dairy cow and calf. 1. Separation at 6 h, 1
      day and 4 days after birth.
AB  - The aim of this study was to evaluate the effects of age of separation on the
      behavioural responses of the dairy calf and cow. Calves were separated from their
      dams 6 h, 1 day, or 4 days after birth (n=9 cow-calf pairs in each of the 3
      treatment groups) and behaviour was video and audio taped from 1 h before
      separation to 21 h after separation. In the hour immediately before separation,
      we found that the younger calves tended to call and move more in the pen, and
      spent more time standing than the older calves, but after separation these trends
      reversed. Calves separated at older ages made significantly more movements in the
      pen (P<0.05), spent more time standing (P<0.05) and spent more time with the head
      out of the pen (P<0.01) than calves separated soon after birth. We observed a
      similar pattern for the cows. Before separation, cows with younger calves moved
      more frequently about the pen (P<0.05), and called at much higher rates (a mean
      of 40.7 calls during 40 min for cows on the 6-h treatment, vs. 0.2 calls for cows
      in the 4-day group; P<0.001). After separation, cows in the 4-day group called at
      approximately four times the rate of those separated at 6 h or 1 day (P<0.01).
      Moreover, the calls produced by cows separated later had a significantly higher
      fundamental frequency (P<0.001) and a lower emphasized harmonic (P<0.02) than the
      calls of cows separated from calves soon after birth. There was no difference
      between treatment groups in the other behavioural measures, either before or
      after separation. Calves separated at older ages tended to require fewer days of
      treatment for scouring, but calf weight gain and cow milk production did not
      differ among treatment groups. In conclusion, behavioural responses of both the
      cow and calf increase in relation to calf age at separation. However, there may
      be health advantages associated with delayed separation that compensate for the
      increased behavioural response.

PMID- 10906403
TI  - Behaviour and leg injuries in dairy cows kept in cubicle systems with straw
      bedding or soft lying mats.
AB  - In order to reduce straw input, soft lying mats are used increasingly instead of
      straw bedding in cubicle systems for dairy cows. This study aimed at comparing
      different types of soft lying mats with straw bedding regarding cow behaviour and
      leg injuries. Data were collected on five farms with straw bedding and on 13
      farms using four types of soft lying mats consisting of different materials. On
      each farm, lying behaviour of 10 cows was recorded automatically during 3 days by
      means of a pneumatically operated resting sensor fitted in a belt. In addition,
      standing up and lying down behaviour of cows was quantified by direct
      observations, and all cows on a given farm were checked once for leg
      injuries.There were no significant differences between cows kept in cubicle
      systems with soft lying mats and straw bedding regarding the total time spent
      lying per day and the number of lying bouts per day. Standing up and lying down
      behaviour also did not differ between cows with access to soft lying mats and
      straw bedding. Leg injuries were most frequent in the tarsal and carpal joints.
      Cows kept in cubicle systems with soft lying mats had a significantly higher
      incidence of both hairless patches more than 2 cm in diameter (P<0.001) and scabs
      or wounds less than 2 cm in diameter (P<0.001) located in the tarsal joints than
      cows in cubicle systems with straw bedding. With the carpal joints, on the other
      hand, the incidence of leg injuries did not differ significantly between these
      two housing conditions. In conclusion, the results of this study indicate that
      soft lying mats are equivalent to straw bedding in terms of cow behaviour but
      less favourable with respect to leg injuries located in the tarsal joints.

PMID- 10906404
TI  - Short-term changes in eating patterns explain the effects of condensed tannins on
      feed intake in heifers.
AB  - Ingestion of condensed tannins decreases feed intake in ruminants. Polyethylene
      glycol (PEG) forms high-affinity complexes with tannins. In two experiments
      carried out on Holstein heifers, quebracho (Q) from the Aspidosperma quebracho
      served as source of condensed tannins. The aims of the study were (i) to quantify
      the effect of Q on feed intake and eating behaviour in cattle fed complete mixed
      diets (CMDs); (ii) to clarify if changes induced in ingestive behaviour and feed
      intake by Q in cattle can be reversed by feeding PEG; and (iii) to clarify if the
      decrease in feed intake is associated with short-term (astringency, post
      ingestive malaise) or longer-term effects. In experiment 1, 500 g/day of Q was
      found to be the minimal dose that decreased feed intake in heifers. A ratio of
      PEG:Q equal to 1:12.5 did not fully restore feed intake. In experiment 2, four
      heifers received a random sequence of four rations in a Latin-square design with
      feeding cycles of ca. 7 days: CMD containing no supplements (C), or supplemented
      with 625 g/day of Q without PEG (Q), with 625 g/day of Q and 250 g/day of PEG (Q
      PEG), or with 250 g/day of PEG without Q (PEG). Individual rations were
      continuously weighed in the trough and the behaviour of heifers was observed for
      180 min after distribution of CMD. Overall, feeding Q was associated with lowered
      feed intake and shorter duration of eating bouts, mainly of the first eating
      bout, immediately after distribution of the diet. A larger portion of the diet
      was consumed subsequent to 180 min after distribution in Q-fed heifers. Eating
      rate and the water to food ratio were not affected by Q. The effects of Q on feed
      intake were attenuated by feeding PEG. Heifers adapted effectively to condensed
      tannins by increasing the number of eating bouts and the portion of diet consumed
      subsequent to 180 min after distribution, so that no differences in feed intake
      were noted on the last day of each feeding cycle. Data are interpreted to show
      that: (i) negative effects of Q on feed intake derive from astringency of CT and
      short-term post-ingestive malaise; (ii) the increased number of eating bouts and
      their wider partition throughout the day are means to preserve the ruminal
      environment in Q-fed heifers; (iii) PEG has the potential to neutralize negative
      effects of condensed tannins in cattle.

PMID- 10906405
TI  - Deprivation of straw bedding alters PGF(2alpha)-induced nesting behaviour in
      female pigs.
AB  - Sows are highly motivated to build a maternal nest on the day preceding
      parturition. A model for nest building has been established in pigs, in which
      exogenously administered prostaglandin F(2alpha) (PGF(2alpha)) may be used to
      elicit nesting behaviour in cyclic, pseudopregnant and pregnant pigs. The aim of
      this experiment was to examine the effects of deprivation of straw bedding on
      PGF(2alpha)-induced nest building in pseudopregnant Large White gilts. Oestradiol
      valerate injections (5 mg/day) were given on days 11-15 of the oestrous cycle to
      induce pseudopregnancy. The pigs were housed individually in a pen (2.8x1.7 m)
      and provided with 2-kg fresh straw each day. On the test day, on day 46 or 47 of
      pseudopregnancy, half of the pigs were deprived of straw (substrate effect) and
      they were injected intramuscularly with saline or 15 mg of PGF(2alpha) (Lutalyse,
      Upjohn) (treatment effect) allocated in a Latin-square design. Behaviour was
      recorded onto video tapes for 1 h either side of treatment for analysis using a
      computerised event recorder. PGF(2alpha)-treated pigs housed in bare or strawed
      pens showed significantly higher frequencies of pawing and rooting, and stood for
      longer than saline-treated controls. This treatment effect has been previously
      shown to be comparable to pre-partum nest building. The removal of straw
      significantly reduced the frequency of pawing and the duration of rooting by
      PGF(2alpha)-treated pigs. The results demonstrate that nesting behaviour can be
      initiated by exogenously administered PGF(2alpha) and is further modified by the
      provision of straw. This suggests that PGF(2alpha)-induced nesting behaviour is
      subject to environmental feedback.

PMID- 10906406
TI  - Behavioural evaluation of methods for assessing fear responses in weaned pigs.
AB  - Models of anxiety and fear of novelty were evaluated using correlations and
      principal component analysis. A total of 84 pigs (LandracexYorkshire) from nine
      different litters were subjected to a tonic immobility (TI) test at the age of
      2.5 weeks, an elevated plus-maze (EPM) at the age of 6 weeks, a light/dark (L/D)
      exploration test at the age of 7 weeks and an open-field (OF) test at the age of
      8 weeks.The first component from the principal component analysis had the highest
      correlation with number of entries into open arms in the EPM but was also highly
      correlated to variables from the other three tests confirming a common aversion
      related element in the four experimental tests. The second component was
      negatively correlated with percent entries into and time spent on open arms in
      the EPM, but positively correlated with the number of entries into closed arms in
      the same test, number of lines crossed in the OF and time spent in the lit
      compartment of the L/D test. The last point illustrates a negative relationship
      between "anxiety" and "activity" in the EPM and OF. To achieve purer measures of
      fear of novelty and activity in the tests, the components were rotated using the
      Varimax criterion. The rotated factor pattern demonstrated a simple structure
      where variables related to "anxiety" or "fear of novelty" (i.e., percent entries
      into open arms and time spent on open arms of the EPM) had the highest loading on
      factor 1, whereas variables related to activity (i.e., number of entries into the
      closed arms in the EPM, number of lines crossed in the OF and time spent in the
      lit compartment of the L/D test) had the highest loading on factor 2. TI duration
      loaded more strongly on factor 1 ("fear of novelty") than on factor 2
      ("activity"), but did not represent any pure measure of either fear of novelty or
      activity.In conclusion, all of the test variables were related to one another.
      Open-arm avoidance represented the purest measure of fear of novelty, whereas
      entries into closed arms and number of lines crossed in the OF were the purest
      measures of activity. The EPM appeared to provide the best way to separate the
      fear of novelty and activity-related elements, indicating that the EPM may be a
      useful behavioural model of fear of novelty or avoidance in pigs.

PMID- 10906407
TI  - Threat assessment by domestic ducklings using visual signals: implications for
      animal-machine interactions.
AB  - There are increasing opportunities for robots to work amongst animals in
      agricultural systems. One potential application is in herding animals prior to
      catching or transportation. An effective herding robot must be able to interrupt
      ongoing animal behaviour without causing panic or flight reactions. The extent to
      which different approaching stimuli interrupted the feeding behaviour of pairs of
      domestic ducklings was examined to assess their suitability as herding stimuli.
      Experiment 1 assessed the responses of ducklings to an approaching human (the
      most likely current herding stimulus), a vertical cylinder (a stimulus with the
      minimum features of a simple robot) and a model fox (simulating the more natural
      features of a predator). Interruption of feeding was greatest in response to the
      human and least to the cylinder. Experiment 2 found no significant difference in
      the extent to which feeding was interrupted when facial appearance and head
      orientation of the model fox were manipulated. Experiment 3 examined whether
      biologically realistic features of the model fox affected duckling response. At a
      distance of 7 m, photographs of the model fox interrupted feeding behaviour as
      much as the model itself. However, at a distance of 1 m, the model fox caused
      significantly more feeding interruption than an intact photograph. A fragmented
      photograph caused the least interruption of feeding behaviour.

PMID- 10906408
TI  - Synthesis and structure-affinity relationships of 1,3, 5-alkylsubstituted
      cyclohexylamines binding at NMDA receptor PCP site.
AB  - A series of 1,3,5-alkylsubstituted cyclohexylamines 2 were synthesized as ligands
      for the N-methyl-D-aspartate (NMDA) receptor phencyclidine (PCP) binding site.
      Pure diastereomers with defined configuration of amino group 2-ax and 2-eq were
      obtained. The optimal size of 1,3,5-substituents was determined for
      cyclohexylamines 2 with an equatorial amino group in the lowest energy
      conformation using Hansch analysis. According to the data, the lipophilic part of
      cyclohexylamines 2 does not discriminate between hydrophobic regions of the PCP
      binding site but rather recognizes this site as a whole lipophilic pocket.

PMID- 10906409
TI  - Homology-based molecular modelling of PLP-dependent histidine decarboxylase from
      Mmorganella morganii.
AB  - The 3-D structural information is a prerequisite for a rational ligand design. In
      the absence of experimental data, model building on the basis of a known 3-D
      structure of a homologous protein is at present the only reliable method to
      obtain structural information. A homology model building study of the pyridoxal
      5'-phosphate (PLP)-dependent histidine decarboxylase from Morganella morganii
      (HDC-MM) has been carried out based on the crystal structure of the aspartate
      aminotransferase from Escherichia coli (AAT-EC). The primary sequences of AAT-EC
      and HDC-MM were aligned by automated alignment procedure. A 3-D model of HDC-MM
      was constructed by copying the coordinates of the residues from the crystal
      structure of AAT-EC into the corresponding residues in HDC-MM. After energy
      minimization of the resulting 3-D model of HDC-MM, possible active site residues
      were identified by fitting the substrate (l-histidine) into the proposed active
      site. In our model, several residues, which have an important role in the AAT-EC
      active-site, are located in positions spatially identical to those in AAT-EC
      structure. The back-bone of the modelled active site pocket is constructed by
      residues; Gly-92, Gly-93, Thr-93, Ser-115, Asp-200, Ala-202, Ser-229 and Lys-232
      together with residues Asn-8, His-119, Thr-171, His-198, Leu-203, His-231, Ser
      236 and Ile-238. In the ligand binding site, it appears that the HDC-MM model
      will position l-histidine (substrate) in the area consisting of the residues; Glu
      29, Ser-30, Leu-38, His-231 and Lys-232. The nitrogen atom of the imidazole ring
      (N2) of the substrate is predicted to interact with the carboxylate group of Ser
      30. The alpha-carboxylate of histidine points toward the Lys-232 to have
      electrostatic interaction with its side chain nitrogen atom (N(Z)). In
      conclusion, this combination of sequence and 3-D structural homology between AAT
      EC and HDC-MM model could provide insight in assigning the probable active site
      residues.

PMID- 10906410
TI  - Molecular modelling and conformational analysis of novel glycoprotein (Gp)
      IIb/IIIa antagonists. Molecular orbital calculation and the condensed
      heterocyclic derivatives.
AB  - A naphthalene compound was chosen as lead compound to develop a new series of
      fibrinogen receptor antagonists. Eight new compounds with different condensed
      heterocyclic parts were prepared and their in vitro activities were evaluated. 5
      Amidinobenzofuran compound 2, 6-amidinobenzothiophene 7, and 5-amidinofuro[2,3
      b]pyridine 8 were more active than lead compound 1. Molecular orbital calculation
      studies suggested the presence of a preferred spatial orientation between the
      amidine and the carboxylic acid.

PMID- 10906412
TI  - New highly potent dipeptidic growth hormone secretagogues with low molecular
      weight.
AB  - Based on NN703, low molecular weight growth hormone secretagouges (GHSs) with a
      reduced number of hydrogen binding sites were designed by removal of the C
      terminal amide group. The compounds were highly potent in combination with high
      efficacy in a rat pituitary cell assay, being characterized with EC(50) values
      down to 0.8 nM. Selected compounds were tested in in vivo animal models. The oral
      bioavailability in dogs was 16-44%. Also, the ED(50) values of the compounds were
      determined both in dog and swine.

PMID- 10906411
TI  - Design of dimeric peptides obtained from a subdominant Epstein-Barr virus LMP2
      derived epitope.
AB  - The latent membrane protein 2 (LMP2) is expressed in EBV-associated tumours. LMP2
      is a target of HLA-A2 restricted EBV-specific CTL responses and consequently it
      may represent a good target for specific CTL-based immunotherapies. However, the
      efficacy of such therapy is limited by the poor immunogenicity of the protein
      that induces weak cytotoxic T lymphocyte (CTL) responses directed against the
      CLGGLLTMV (CLG) epitope. Indeed, the CLG peptide presents low affinity for HLA-A2
      and does not produce stable complexes. Therefore we synthesized and tested CLG
      dimeric analogues with the purpose of characterizing new compounds with the
      capacity to bind HLA-A2 molecules. By these studies we have identified a few
      peptides which, compared to the natural epitope, showed higher affinity for HLA
      A2 molecules and superior capacity to form a complex. These dimeric peptides may
      have the potential to induce efficient CTL responses directed to the natural
      epitope.

PMID- 10906413
TI  - Partial resistance of E. coli mutants against 2, 4-diamino-5-benzylpyrimidines by
      interactions with bacterial membrane lipopolysaccharides. Derivation of
      quantitative structure-binding relationships.
AB  - A series of previously synthesized 2,4-diamino-5-benzylpyrimidines, inhibitors of
      bacterial dihydrofolate reductase (DHFR) showed decreased inhibition of E. coli
      cultures, despite increased inhibitory activity against DHFR. Preliminary studies
      using E. coli mutants with different degrees of outer membrane deficiencies
      suggested that the decrease in activity was partly due to inactivation because of
      binding to outer membrane constituents. In the present study antibacterial
      activities of the benzylpyrimidines have been systematically determined as a
      function of cell membrane defects in E. coli using bacterial growth kinetic
      techniques. It has been shown that the observed differences in activity were not
      due to different binding affinities to the target enzyme of the mutants.
      Lipopolysaccharides have been extracted from the mutants and used in binding
      studies by ultrafiltration, photometric and NMR techniques. The observed
      differences in binding affinity to the lipopolysaccharides have been related to
      the differences in the lipophilic properties and molecular weight of the
      substituents. Quantitative structure-activity relationships have been derived.
      The results of the study show the importance of drug-membrane interactions for
      the rational development of antibacterials.

PMID- 10906414
TI  - Synthesis of some thiazolyl-pyrazoline derivatives and preliminary investigation
      of their hypotensive activity.
AB  - Some 1-(4-arylthiazol-2-yl)-3,5-diaryl-2-pyrazoline derivatives were synthesized
      by reacting 1-thiocarbamoyl-3,5-diaryl-2-pyrazoline derivatives with
      phenacetylbromide in ethanol. The structural elucidation of the compounds were
      performed by IR, 1H-NMR and Mass spectral data and elemental analyses. The
      hypotensive activities of 13 compounds were evaluated by using the tail-cuff
      method. All examined compounds showed appreciable hypotensive activities.
      Clonidine was used as reference substance in the pharmacological evaluation.

PMID- 10906415
TI  - Design and synthesis of alpha,beta-unsaturated carbonyl compounds as potential
      ACE inhibitors.
AB  - The alpha,beta-unsaturated amide that is incorporated into the basic structural
      frame of a simple substrate molecule of angiotensin converting enzyme was found
      to serve as a Michael acceptor for the catalytic carboxylate of Glu-127,
      inhibiting the enzyme irreversibly.

PMID- 10906416
TI  - Report by the editors

PMID- 10906417
TI  - Genotoxicity of several clinically used topoisomerase II inhibitors.
AB  - DNA topoisomerase II is an essential nuclear enzyme that modulates DNA topology
      during multiple cellular processes such as DNA replication and chromosome
      segregation. Several important clinical antitumor drugs and antibiotics act
      through inhibition of topoisomerase II. There are a number of different steps in
      the action of topoisomerase II, all of which are potential targets for inhibition
      through drugs and also for cellular and genetic toxicity as well as for
      mutagenesis. We have investigated and compared the genotoxicity and mutagenicity
      of the mechanistically different topoisomerase II inhibitors m-amsacrine,
      mitoxantrone, etoposide, genistein, ICRF 193, and berenil using the in vitro
      micronucleus test, single cell gelelectrophoresis (comet assay) and the mutation
      assay (tk-locus) in L5178Y mouse lymphoma cells. All six compounds induced
      micronuclei and all except berenil were mutagenic. M-amsacrine, mitoxantrone,
      etopside and genistein induced DNA migration in the comet assay, whereas ICRF 193
      was only weakly positive and berenil was negative in this test. Our results are
      in good agreement with the compounds' proposed mechanisms of interaction with
      topoisomerase II.

PMID- 10906418
TI  - The relationship between stress protein induction and the oxidative defense
      system in the rat hippocampus following kainic acid administration.
AB  - The time and dose-dependent effects of kainic acid (KA) induced excitotoxicity on
      the oxidative defense system and the relationship to the induction of stress
      proteins were investigated in the rat hippocampus. Male Long-Evans rats were
      injected subcutaneously with 5.0, 7.5, or 10 mg KA/kg. Rats were sacrificed and
      the hippocampus removed and processed for biochemical and electrophoretic
      analysis. The activity of glutathione peroxidase (GPx) increased significantly at
      the 5 mg KA/kg dose, while malondialdehyde (MDA) levels significantly increased
      at 7.5 mg KA/kg when measured at 24 h. A dose of 10 mg KA/kg depleted
      significantly hippocampal glutathione (GSH) levels at 8, 16 and 24 h post
      treatment while GPx activity was increased significantly at 2, 4, 8 and 16 hr
      post-treatment. The 10 mg KA/kg increased significantly hippocampal MDA levels at
      2 h post-treatment and decreased significantly thereafter. The induction of
      stress proteins increased in a dose and time dependent manner. The expression of
      Hp72 and Hsp32 increased significantly at 16 h with a maximum induction observed
      at 24 h post-treatment. The data suggests that KA toxicity is mediated through
      the formation of reactive oxygen species resulting in alterations in the
      oxidative defense system. The expression of stress proteins following KA
      administration may reflect a concomitant but alternate response to excitotoxic
      events.

PMID- 10906419
TI  - K6/ODC transgenic mice as a sensitive model for carcinogen identification.
AB  - Ornithine decarboxylase (ODC), an important enzyme in the polyamine biosynthetic
      pathway, is aberrantly regulated in many epithelial tumors of rodents and humans.
      In murine skin, it has been shown that ODC overexpression provides a sufficient
      condition for tumor promotion. Therefore, we hypothesized that K6/ODC transgenic
      mice in which ODC overexpression was targeted to hair follicle keratinocytes
      might provide a sensitive model for identifying genotoxic carcinogens. Ten known
      carcinogens or noncarcinogens have been tested in the model so far and results
      are highly concordant with 2-year rodent bioassays (100% concordant). More
      importantly, each of two chemicals tested that is recognized as a human
      carcinogen was identified as a carcinogen in K6/ODC transgenic mice. In addition,
      7, 12-dimethylbenz(a)anthracene (DMBA) dose response studies indicated that even
      at a very low dose, 2 nmol, a high percentage of mice (50%) had already developed
      tumors 8 weeks after treatment. We conclude that the K6/ODC transgenic mouse
      model is very sensitive to topical application of genotoxic carcinogens and could
      therefore be a useful mouse model for carcinogen identification and chemical risk
      assessment.

PMID- 10906420
TI  - Subchronic administration of sublethal doses of thallium to rats: effects on
      distribution and lipid peroxidation in brain regions.
AB  - Occupational exposure to thallium (Tl+) is known to be responsible for severe
      neurological manifestations in humans, including ataxia and paralysis; however,
      little is known yet about the precise mechanism of toxicity elicited by this
      heavy metal at sublethal doses and its brain distribution after chronic or
      subchronic exposures resulting from environmental contamination. In order to
      evaluate the levels of Tl in rat brain regions after a subchronic administration
      (30 days) of sublethal doses of Tl (I) acetate: 0.8 mg/kg (1/40 of LD(50)), 1.6
      mg/kg (1/20 of LD(50)), we measured the concentrations of Tl by atomic absorption
      spectrophotometry. A possible role of oxidative injury in the pattern of toxicity
      exerted by Tl in the same brain regions, was also studied. Lipid peroxidation
      (LP) as a current marker of oxidative stress, was estimated by the generation of
      lipid fluorescent products. Higher concentrations of Tl were observed in brain
      tissue from adult rats treated with 1.6 mg/kg, as compared to those treated with
      0.8 mg/kg. However, no differential distribution of Tl among regions was observed
      after administration of 0.8 mg/kg dose to rats, nor after 1. 6 mg/kg dose. We
      also found significant changes in LP both in corpus striatum and cerebellum from
      rats treated daily with 0.8 mg/kg Tl, whereas all regions from rats treated with
      1.6 mg/kg Tl exhibited enhanced LP as compared to control. These findings suggest
      an active role of free radicals and oxidative events involved in the pattern of
      toxicity after exposure to sublethal doses of Tl, which are associated with
      regional susceptibility of the brain to this metal.

PMID- 10906421
TI  - Effect of lead on Sertoli-germ cell coculture of rat.
AB  - Mixed cultures of Sertoli and germ cells were prepared from rat testes and their
      response to lead (Pb) was studied. Cultures consisted of a monolayer of Sertoli
      cells to which clusters of germ cells were attached. The effect of Pb added as
      lead acetate was tested at 0.0, 0.4, 4.0 and 40.0 microM for 24 and 48 h
      intervals. Addition of Pb to the culture medium caused germ cells to
      progressively detach from the Sertoli cell monolayer into the medium in a
      concentration and duration dependent manner Viability of the detached cells as
      judged by trypan blue exclusion test showed a decrease with increase in time and
      concentration of Pb. Significant leakage of lactate dehydrogenase (LDH) was
      recorded in the culture media only at the higher concentrations of 4.0 and 40.0
      microM. Thus Pb at the doses tested induced cytotoxicity in rat Sertoli-germ cell
      coculture.

PMID- 10906422
TI  - Intraperitoneal administration of doxorubicin encapsulating liposomes against
      peritoneal dissemination.
AB  - To improve therapy for peritoneal dissemination, and the distributions of
      doxorubicin (DOX) in the abdominal cavity, solid tumor and normal tissues after
      intraperitoneal administration of DOX-encapsulating liposomes was examined. In
      small negatively charged liposomes, lipid composition did not affect the
      clearance or stability of liposomes in the abdominal cavity. Whereas, for the
      treatment of solid tumor and the reduction of side effects, L-alpha
      distearoylphosphatidylcholine-containing liposomes were most effective. On the
      other hand, large liposomes (DS(L)-Lip) were most abundant in the abdominal
      cavity. As the DOX levels in the heart, liver and solid tumor after DS(L)-Lip
      injection were lower than the corresponding values for the small liposome group,
      we considered that DS(L)-Lip were disrupted in the abdominal cavity and DOX was
      released from the liposomes. DS(L)-Lip remain in the abdominal cavity for a long
      time inducing cytotoxicity. The survival of Ehrlich ascites carcinoma-bearing
      mice was considered to be prolonged by DS(L)-Lip. Liposomes, both small and large
      in size appear to be effective against solid tumors except in the abdominal
      cavity, and against peritoneal dissemination in the abdominal cavity,
      respectively.

PMID- 10906423
TI  - Antioxidant effect of onion oil (Allium cepa. Linn) on the damages induced by
      nicotine in rats as compared to alpha-tocopherol.
AB  - The beneficial effects of onion oil as an antioxidant has been assessed in
      nicotine administered rats by studying whether the peroxidative damage caused by
      nicotine can be effectively combated with the onion oil and the effects compared
      to vitamin E, a highly efficient antioxidant. Lipid peroxidation products and
      antioxidant defence system have been studied in liver, lungs, and heart. The rats
      were injected with nicotine (0.6 mg/kg body wt.) and simultaneously given onion
      oil (100 mg/kg body wt.) or vitamin E (100 mg/kg body wt.) for 21 days.
      Concentration of free fatty acids, TBA reactive substances (TBARS), conjugated
      dienes and hydroperoxides were significantly increased in the tissues of nicotine
      treated rats as compared to normal rats. Onion oil supplemented to nicotine
      treated rats showed increased resistance to lipid peroxidation and the effect was
      near to that of vitamin E fed rats. The activity of catalase and superoxide
      dismutase decreased in nicotine treated rats. Antioxidants-glutathione content,
      vitamin C and retinol showed no significant difference but liver vitamin E
      content significantly decreased in nicotine treated rats. On onion oil or vitamin
      E supplementation, the concentration of antioxidants were significantly raised in
      all the tissues studied, however, a significantly increased concentration of
      glutathione, vitamin E and retinol was noticed in vitamin E+nicotine treated
      rats. Thus, these results indicate that onion oil is an effective antioxidant
      against the oxidative damage caused by nicotine as compared to vitamin E.

PMID- 10906424
TI  - Role of perivenous hepatocytes in taurolithocholate-induced cholestasis in vivo.
AB  - The magnitude of cholestasis induced by taurolithocholic acid (TLCA) and its
      relationship with phase I metabolism were analyzed in rats treated with
      bromobenzene (BZ), a chemical that causes selective necrosis of perivenous (zone
      3) hepatocytes. Forty-eight hours after BZ administration (600 mg/Kg bw), a
      single dose of 20 micromol/Kg bw of TLCA was injected. Bile was collected during
      180 min and bile flow and total bile acid excretion rate were determined. Biliary
      bile acid composition was analyzed by gas-liquid chromatography-mass
      spectrometry. BZ administration did not affect the development of TLCA-induced
      cholestasis, but exacerbated the bile acid-induced decrease in bile flow during
      the period of recovery from cholestasis. Biliary excretion of total bile acids
      after TLCA injection relative to basal value was not effected by BZ. The analysis
      of bile acid composition in bile revealed that TLCA was partially converted to
      hyodeoxycholic and muricholic acids. The cumulative excretion of all exogenous
      bile acids and their contribution to the composition of the biliary bile acid
      pool were not substantially affected by zone 3 necrosis, suggesting that
      synthesis and secretion of hydroxylated derivatives of TLCA were maintained by
      zone 1 and 2 hepatocytes. The relative content of endogenous bile acids was not
      affected by BZ during TLCA-induced cholestasis. Thus, it seems unlikely that the
      exacerbation of the cholestasis in BZ-treated rats is due to different choleretic
      properties and/or toxicity of the bile acid pool.

PMID- 10906425
TI  - Structure-activity relationships in the induction of DNA-protein cross-links by
      hematotoxic ring-opened benzene metabolites and related compounds in HL60 cells.
AB  - Previous studies from our laboratory have demonstrated the formation of DNA
      protein cross-links (DNAPC), a potentially cytotoxic and genotoxic lesion induced
      by many leukemogenic agents, in bone marrow cells of mice administered benzene,
      however, reactive benzene metabolites involved in DNAPC formation by benzene have
      not been characterized. The present studies examined DNA PC formation in HL60
      cells treated with trans,trans-muconaldehyde (MUC), a hematotoxic ring-opened
      metabolite of benzene, as well as with MUC metabolites and structurally related
      compounds. Using a K(+)/SDS precipitation assay for DNAPC determination,
      concentration- and time-dependent increases in DNAPC formation were observed 2
      and 4 h after treatment of HL60 cells with 50, 75 and 100 microM MUC. No
      increases in DNAPC levels were measured in HL60 cells 4 h after treatment with
      the MUC metabolites 6-hydroxy-trans,trans-2,4-hexadienal (HO-M-CHO), 6-oxo
      trans,trans-2,4-hexadienoic acid (CHO-M-COOH), or trans,trans-muconic acid (HOOC
      M-COOH), each at 100 microM. Significant increases in DNAPC levels were observed
      4 h after treatment with 500 and 1000 microM HO-M-CHO, but not CHO-M-COOH. No
      effect on DNAPC levels was observed 4 h after treatment with 100 microM for
      trans, trans-2,4-hexadienal, trans-2-hexenal, hexanal, trans,trans-2, 4
      hexadiene, glutaraldehyde, or acrolein. DNAPC induced by MUC and HO-M-CHO may be
      cytotoxic lesions, as increases in DNAPC levels by these compounds correlated
      with decreases in cell viability. Except for acrolein, compounds not inducing
      DNAPC at 100 microM also did not affect cell viability. These studies suggest
      that both aldehydic carbons of MUC contribute to DNAPC induction, and that the
      presence of alpha,beta-unsaturated double bonds conjugated with the aldehyde
      groups increases the ability of MUC to induce DNAPC relative to the saturated
      dialdehyde glutaraldehyde.

PMID- 10906426
TI  - Subcutaneous treatment of p-tert-octylphenol exerts estrogenic activity on the
      female reproductive tract in normal cycling rats of two different strains.
AB  - Effects of p-tert-octylphenol (OP), an endocrine disrupting chemical (EDC), on
      the female reproductive tract of normal cycling Fischer 344 (F344) and Donryu
      rats were investigated. OP was subcutaneously injected at concentrations of 12.5,
      25, 50 or 100 mg/kg for 28 days. The most notable changes were the disappearance
      of normal cyclicity in the 50 mg/kg or more OP-treated groups of both the
      strains, and the appearance of persistent estrus (PE) evident on examination of
      vaginal smears in the 100 mg/kg groups of both the strains, the effects being
      time- and dose-dependent. In PE rats of both the strains, the uterine morphology
      deviated from the normal for each estrous stage of the cycling rats, and
      proliferation in the endometrium was slightly increased. The data for uterine
      weights, luminal epithelial cell-heights and/or numbers of epithelial cells in
      the endometrium demonstrated equivocal alteration. In both the strains, the serum
      17beta-estradiol (E2) levels were decreased with 50 mg/kg of OP or more. Serum
      concentrations of the administrated chemical were dose and duration-dependently
      increased in all the treated groups of both the strains. The results demonstrate
      that subcutaneous administration of OP at doses of 50 mg/kg or more exerts time-
      and dose-dependent estrogenic activity on the reproductive tract of normal
      cycling female Donryu and F344 rats, indicating similar qualitative sensitivity
      to the effects in both the strains. Vaginal cytology may be the most sensitive
      endpoint for the detection of estrogenic activity of potential EDCs using adult
      cycling rats.

PMID- 10906427
TI  - Pattern of deposition of stainless steel welding fume particles inhaled into the
      respiratory systems of Sprague-Dawley rats exposed to a novel welding fume
      generating system.
AB  - In order to investigate occupational diseases related to welding fume exposure,
      such as nasal septum perforation, pneumoconiosis and manganese intoxication, we
      built a welding fume exposure system that included a welding fume generator,
      exposure chamber and fume collector. The fume concentrations in the exposure
      chamber were monitored every 15 min during a 2-h exposure. Fume (mg/m(3))
      concentrations of major metals, including Fe, Mn, Cr, and Ni were found to be
      consistently maintained. An acute inhalation toxicity study was conducted by
      exposing male Sprague-Dawley rats to the welding fumes generated in this
      apparatus by stainless steel arc welding. The rats were exposed in the inhalation
      chamber to a welding fume with a concentration of 62 mg/m(3) total suspended
      particulates for 4 h. Animals were sacrificed at 4 h and at 1, 3, 7, 10, and 14
      days after exposure. Histopathological examinations were conducted on the
      animals' upper respiratory tracts, including the nasal pathway and the conducting
      airway, and on the gas exchange region including the alveolar ducts, alveolar
      sacs, and alveoli. Diameters of fume particles varied from 0.02 to 0.81 microm
      and were distributed log normally, with a mean diameter of 0.1 microm and
      geometric standard deviation of 1.42. Rats exposed to the welding fume for 4 h
      did not show any significant respiratory system toxicity. The mean particle
      diameter of 0.1 microm resulted in little adsorption of the welding fume
      particles in the upper respiratory tract. Particle adsorption took place
      principally in the lower respiratory tracts, including bronchioles, alveolar
      ducts, alveolar sacs, and alveoli.

PMID- 10906428
TI  - Dopamine toxicity following long term exposure to low doses of 3-nitropropionic
      acid (3-NPA) in rats.
AB  - A toxin produced by legumes of the genus Astragalus and Arthrinium fungi, 3-NPA
      is a suicide inhibitor of succinate dehydrogenase and causes acute encephalopathy
      and late onset dystonia. It has been suggested that dopamine (DA) toxicity plays
      a role in 3-NPA induced brain damage. In order to simulate natural conditions of
      toxicant intake, adult, male, Sprague-Dawley rats were exposed to 3-NPA weekly
      for 24-h periods at 10 and 20 mg/40 ml in drinking water. This dosing regimen
      continued for 3 months with animals from both high and low dose groups sacrificed
      at the end of each month. Dopamine and its metabolites, 3,4
      dihydroxylphenylacetic acid (DOPAC) and homovanillic acid (HVA), were assessed by
      HPLC-EC in the frontal cortex (FC) and caudate nucleus (CN). Increases of DA
      concentration were seen in both low and high dose groups in the CN after 1 and 3
      months of dosing and in the FC after 2 months of exposure. An increase in DA
      turnover was observed in the CN of the high dose group following 2 months of
      dosing. Data suggest an activation of the dopaminergic system after long-term,
      intermittent exposure to 3-NPA. The production of radical oxygen species
      associated with DA metabolism may contribute to 3-NPA-induced neurotoxicity.

PMID- 10906429
TI  - Overexpression of G1/S cyclins and PCNA and their relationship to tyrosine
      phosphorylation and dephosphorylation during tumor promotion by metanil yellow
      and malachite green.
AB  - Metanil yellow (MY) and Malachite green (MG) are textile dyes, which, despite the
      ban, occur unscrupulously as food colouring agents. Accordingly they constitute a
      serious public health hazard and are of sufficient environmental concern. We have
      earlier reported that both MY and MG have tumor promoting effects on the
      development of hepatic preneoplastic lesions induced by N-nitrosodiethylamine in
      rats. In order to understand the possible mechanism(s) by which metanil yellow
      (MY) and malachite green (MG) promotes liver tumor development, we have studied
      the tyrosine phosphorylation and protein phosphatases during tumor promotion. We
      have also investigated the possible overexpression of G1/S cyclins and PCNA
      during tumor promotion by MY and MG. The present investigation indicates that
      enhanced tyrosine phosphorylation is associated with no change in levels of
      tyrosine protein phosphatases. We have also observed an increase in the
      expression of PCNA and G1/S cyclins during tumor promotion. These factors
      collectively may contribute to the abnormal cell proliferation during tumor
      promotion by MY and MG.

PMID- 10906430
TI  - Redistribution of accumulated 2,3,7,8-tetrachlorodibenzo-p-dioxin during
      coxsackievirus B3 infection in the mouse.
AB  - The tissue redistribution of accumulated 2,3,7, 8-tetrachlorodibenzo-p-dioxin
      (TCDD) during infection was studied in adult male A/J mice using a common human
      virus coxsackievirus B3. Before infection (day 1), all mice were injected
      intraperitoneally (i.p.) with 1 microCi 3H-TCDD, corresponding to 0.5 microg TCDD
      kg(-1). One group was sacrificed before virus inoculation (day 0). Of the
      remaining mice, one subgroup was inoculated i.p. with CB3 virus while the other
      subgroup served as a noninfected control. On days 0, 4 and 7, the spleen, thymus,
      heart, pancreas, liver, white and brown adipose tissue, skeletal muscle, lung,
      kidney, brain, adrenals, thyroid, testes, epididymis and blood were sampled from
      infected and noninfected groups. Liquid scintillation was used to determine the
      3H-TCDD-content of the tissues. The results showed that the accumulated TCDD was
      redistributed due to infection. The major changes occurred in the organs involved
      in the infectious process. In the target organs for coxsackievirus B3 (the
      pancreas and heart), the TCDD concentration peaked in relation to noninfected
      control values, concurrent with the development of inflammatory lesions (P<0.001
      and 0.01, respectively for the heart and pancreas). The TCDD levels in the thymus
      increased three-fold during the infection to an estimated 0.5 pmol g(-1) tissue
      on day 7 of the infection, whereas the levels in noninfected mice did not change
      markedly (P<0.001). In the brain of infected mice, the TCDD concentration
      increased significantly with time, at day 7 reaching two-fold levels in
      comparison with noninfected controls (P<0.001). The findings suggest that a
      common infection causes redistribution of a previously accumulated environmental
      pollutant, resulting in increased concentrations and potentially increased
      toxicity in selected target tissues.

PMID- 10906431
TI  - SOS induction of the recA gene by UV-, gamma-irradiation and mitomycin C is
      mediated by polyamines in Escherichia coli K-12.
AB  - Polyamines are involved in a wide range of cellular metabolism. In this study we
      investigated the effects of polyamines on the SOS induction of the recA gene by
      exposure to UV-, gamma-irradiation and mitomycin C employing polyamine-deficient
      mutant and wild type Escherichia. coli strains carrying recA'::'lacZ
      transcriptional fusion. In the polyamine-deficient mutant, the induction factor
      of the recA gene by UV-, gamma-irradiation and mitomycin C-treatment are about
      3.0-, 2.5- and 4-fold lower, respectively, than those of the wild type. The
      exogenous addition of polyamines restored the reduced induction of the recA gene
      to the wild type level. Tri-amine spermidine effectively restored the recA
      induction to a level similar to the wild type, while being less restored by the
      di-amine putrescine. The restoration of recA induction by polyamines may be
      accomplished in a dose- and charge-dependent manner. Our results strongly suggest
      that polyamines may play an essential role as the SOS inducing mediator following
      exposure to damaging agents in E. coli and provide important information that
      tackles an interesting question in how cells respond to chemical and physical
      stresses.

PMID- 10906432
TI  - Acute exposure to the abused inhalant, isobutyl nitrite, reduced T cell
      responsiveness and spleen cellularity.
AB  - Isobutyl nitrite is an inhalant abused principally by male homosexuals. We have
      reported that subchronic inhalation exposure (45 min/day for 14 days) to 900 ppm
      isobutyl nitrite was immunosuppressive. In the present study, the effects of
      acute exposure to the inhalant were examined. Mice were exposed in an inhalation
      chamber to 900 ppm isobutyl nitrite for 45 min. One day later, spleen cellularity
      was reduced by 39% without selectively depleting CD4(+) or CD8(+) cells. The
      numbers of peripheral blood leukocytes and peritoneal cells were also reduced.
      Following acute inhalation exposure, T cell proliferative responses stimulated
      with allogeneic cells or anti-CD3 and anti-CD28 antibodies were inhibited, while
      mitogen-induced responses were not affected. Purified T cells exposed to the
      inhalant also had compromised responses, suggesting a direct effect on T cells.
      However, the cumulative effects of multiple exposures were necessary to inhibit T
      dependent antibody responses or T cell or macrophage cytotoxicity.

PMID- 10906433
TI  - Damage induced by stannous chloride in plasmid DNA.
AB  - Stannous chloride (SnCl(2)) is widely used in daily human life, for example, to
      conserve soft drinks, in food manufacturing and biocidal preparations. In nuclear
      medicine, stannous chloride is used as a reducing agent of Technetium-99m, a
      radionuclide used to label different cells and molecules. In spite of this,
      stannous chloride is able to generate reactive oxygen species (ROS) which can
      damage DNA. In this work, plasmid DNA (pUC 9.1) was incubated with SnCl(2) under
      different conditions and the results analyzed through DNA migration in agarose
      gel electrophoresis. Our data reinforce the powerful damaging effect induced by
      stannous ion and suggest that this salt can play a direct role in inducing DNA
      lesions.

PMID- 10906434
TI  - Evaluation of skin sensitization potential of jet fuels by murine local lymph
      node assay.
AB  - Jet A and JP-8 are the major jet fuels used in civilian and military (US Air
      Force) flights, respectively. JP-8+100 is a new jet fuel recently introduced by
      the US Air Force. Besides lung exposure, skin is the potential route of exposure
      to jet fuels. The purpose of the present study was to investigate the skin
      sensitization potential of jet fuels (Jet A, JP-8 and JP-8+100) using murine
      Local lymph node assay (LLNA). Female CBA/Ca mice (8-12-weeks-old) were used in
      the study. Dinitrochlorobenzene (DNCB, 0.25% w/v) and paraaminobenzoic acid
      (PABA, 2.5% w/v) were used as positive and negative control, respectively and
      acetone: olive oil (4:1, AOO) was used as the vehicle (control). All three jet
      fuels caused a proliferative activity significantly greater than the control
      (P<0.01). Our results demonstrate that JP-8 is a weak skin sensitizer
      [stimulation index (SI)=3.17]. The SI of Jet A and JP-8+100 were 2.44 and 2.38,
      respectively, hence are not considered as skin sensitizers. Interestingly, the SI
      of JP-8 with butylated hydroxytoluene (BHT) was consistently lower than JP-8,
      though the difference was not statistically significant (P>0.05). BHT, which is
      an antioxidant additive of JP-8+100, reduced the skin sensitization potential of
      JP-8. Furthermore, the lower SI of JP-8+100 could be partially attributed to the
      presence of BHT. The findings reported here suggest that care should be taken to
      minimize dermal exposure to jet fuels especially JP-8 to avoid skin
      sensitization.

PMID- 10906435
TI  - In vitro genotoxicity of ethanol and acetaldehyde in human lymphocytes and the
      gastrointestinal tract mucosa cells.
AB  - The influence of ethanol and acetaldehyde on DNA in human lymphocytes, gastric
      mucosa (GM) and colonic mucosa (CM) was investigated by using the comet assay.
      All kinds of cells were exposed to ethanol and acetaldehyde in two regimens: the
      cells were incubated with either chemical and analysed or they were exposed first
      to ethanol, washed and then exposed to acetaldehyde and analysed. Lymphocytes
      were exposed to ethanol at final concentrations of 30 mM and acetaldehyde at 3
      mM. GM cells were incubated with ethanol at 1 M and acetaldehyde at 100 mM. CM
      cells were exposed to ethanol at 10 mM and acetaldehyde at 100 mM. In combined
      exposure, the cells were subsequently exposed to ethanol and acetaldehyde at all
      combination of the concentrations of the agents. Ethanol caused DNA strand
      breaks, which were repaired during 4 hr, except when this agent was applied in GM
      cells at a concentration of 1 M. A dose-dependent decrease in the tail moment of
      all types of acetaldehyde-treated cells was observed. Similar results were
      obtained when a recognized DNA crosslinking agent, formaldehyde, was used. These
      results suggest that acetaldehyde may form crosslinks with DNA. These crosslinks
      were poorly repaired. CM cells showed the highest sensitivity of all cell types
      to ethanol than lymphocytes and GM cells. There were no differences in the
      sensitivity to acetaldehyde of all the cell types. Our results clearly indicate
      that ethanol and acetaldehyde can contribute to cancers of the digestive tract.

PMID- 10906436
TI  - Protection by free oxygen radical scavenging enzymes against salicylate-induced
      embryonic malformations in vitro.
AB  - Salicylates are among the oldest and most widely used drugs and are known to lead
      to foetal death, growth retardation and congenital abnormalities in experimental
      animals. In this study, the effects of acetyl salicylic acid (ASA), salicylic
      acid (SAL) and sodium salicylate (NaSAL) on early organogenesis and the
      interaction of these molecules with free radicals has been investigated.
      Postimplantation rat embryos were cultured in vitro from day 9.5 of gestation for
      48 hr. ASA, SAL and NaSAL were added to whole rat serum at concentrations between
      0.1 and 0.6 mg/ml. Also, the lowest effective concentration of ASA for all
      parameters (0.3 mg/ml) and the same concentration of NaSAL and SAL was added to
      the culture media in the presence of superoxide dismutase (SOD) (30 U/ml) or
      glutathione (0.5 micromol/ml). The growth and development of embryos was compared
      and each embryo was evaluated for the presence of any malformations. When
      compared to growth of control embryos, the salicylates decreased all growth and
      developmental parameters in a concentration-responsive manner. There was also a
      concentration-related increase in overall dysmorphology, including the incidence
      of haematoma in the yolk sac and neural system, open neural tube, abnormal tail
      torsion and the absence of fore limb bud. When SOD was added in the presence of
      ASA, growth and developmental parameters were improved and there was a
      significant decrease in the incidence of malformations. Addition of SOD also
      decreased the incidence of malformations in the presence of SAL, but did not
      effect the growth and developmental parameters of SAL and NaSAL. There was no
      significant difference between the embryos grown in the presence of these three
      molecules on the addition of glutathione. The effects of salicylates might
      involve free oxygen radicals by the non-enzymatic production of the highly
      teratogenic metabolites 2,3- and 2,5-dihydroxybenzoic acid. An enhanced
      production of these metabolites in embryonic tissues may be directly related to
      the increased risk of congenital malformations.

PMID- 10906437
TI  - Different cytotoxic response to gadolinium between mouse and rat alveolar
      macrophages.
AB  - The cytotoxicity of gadolinium (Gd) chloride was investigated in alveolar
      macrophages (AM) cultured in vitro. A marked difference in the cytotoxic response
      to Gd was found between mouse and rat AM. The viability of rat AM was decreased
      by exposure to Gd at doses more than 3 microM, while mouse AM appeared to be
      resistant even up to 1000 microM Gd exposure. The decrease in the viability of
      rat AM exposed to Gd at doses up to 1000 microM was mitigated by centrifugation
      and filtration of the culture medium containing Gd, or by the treatment of AM
      with lysosomotropic agents such as NH(4)Cl or chloroquine, suggesting that the
      cytotoxic response of rat AM to Gd at doses up to 1000 microM was dependent on
      the intracellular uptake and subsequent dissolution of Gd present in the culture
      medium in colloidal form. The phagocytic activity of mouse AM, evaluated by the
      uptake of latex particles, was higher than that of rat AM. Furthermore,
      quantitative analysis of Gd with inductively coupled plasma-mass spectrometry
      revealed that mouse AM took up a larger amount of Gd than rat AM. Therefore, the
      marked difference in the cytotoxic response to Gd between mouse and rat AM could
      not be attributed to the phagocytic activities for the colloidal form of Gd. The
      cytotoxic sensitivity of AM to Gd present in non-colloidal form was almost the
      same between mouse and rat AM. Therefore, it is suggested that the extent to
      which Gd-colloid phagocytosed is dissolved in the phago-lysosome or the
      subsequent process to exhibit the cytotoxicity may be different between mouse and
      rat AM.

PMID- 10906438
TI  - Cytochrome P450-mediated metabolism and cytotoxicity of aflatoxin B(1) in bovine
      hepatocytes.
AB  - Aflatoxin B(1) (AFB(1)) biotransformation comprises cytochrome P450-mediated
      reactions resulting in hydroxylated and demethylated metabolites as well as
      AFB(1) epoxides. As the latter are highly nucleophilic, the species-specific rate
      of epoxidation and the ability for rapid conjugation to glutathione by
      glutathione S-transferase determines the individual susceptibility to AFB(1).
      Here we show the time- and dose-dependent rate of AFB(1)-metabolism in bovine
      hepatocytes. Aflatoxin M(1) (AFM(1)) is the most prominent metabolite formed
      within the first 2-8 hr of incubation, whereas AFB(1)-dhd is detectable in medium
      mainly after a prolonged incubation period. The delayed formation of AFB(1)-dhd
      corresponds to the cytotoxicity demonstrated by the MTT assay. alpha
      Naphthoflavone and ketoconazole, inhibitors of CYP1A and CYP3A, respectively in
      humans, were used to evaluate the contribution of specific P450 isoenzymes in
      bovine biotransformation of AFB(1). Initial experiments confirmed that alpha
      naphthoflavone and ketoconazole inhibited ethoxyresorufin O-deethylation and
      testosterone 6beta-hydroxylation also in bovine hepatocytes. Both inhibitors
      reduced AFM(1) and AFB(1)-dhd formation concentration dependently, suggesting
      that both enzyme groups contribute to the formation of these metabolites.
      However, the formation of AFM(1) was less inhibited by both compounds than the
      formation of AFB(1)-dhd.

PMID- 10906439
TI  - The role of reduced glutathione and glutathione reductase in the cytotoxicity of
      chromium (VI) in osteoblasts.
AB  - It is accepted that to exert cytotoxicity and carcinogenicity chromium VI has to
      be reduced inside cells. The role of reduced glutathione (GSH) and glutathione
      reductase in the intracellular reduction of Cr VI was investigated using an
      immortalized rat osteoblast cell line, FFC. Alkaline phosphatase activity was the
      index of cytotoxicity measured. To investigate the role of GSH in Cr VI toxicity,
      GSH levels in the cells were elevated by pretreatment with L-cysteine, and
      depleted using buthionine sulfoximine (BSO), an inhibitor of GSH synthesis.
      Intracellular GSH levels were not depleted during the metabolism of Cr VI.
      Depletion of GSH by BSO caused the cells to be more resistant to the toxicity of
      Cr VI, indicating that GSH is involved in reduction of the Cr VI. Inhibition of
      glutathione reductase by carmustine (BCNU) partially protected against the
      cytotoxicity of Cr VI irrespective of the intracellular GSH. The cytotoxic
      response was similar if cells were pretreated with BCNU plus L-cysteine, or with
      BCNU plus BSO, although the GSH levels were markedly different. The results
      indicate that glutathione reductase plays an important role in the intracellular
      reduction of Cr VI in osteoblasts.

PMID- 10906440
TI  - Inductions of fibroblast-like morphology and high growth activity by low-dose CPT
      11 in PC12 cells: role of tenascin.
AB  - The chemotherapeutic agent CPT-11 induces apoptotic cell death in various cells.
      In the present study we examined the effect of CPT-11 in rat pheochromocytoma
      PC12 cells. When PC12 cells were treated with CPT-11, two distinct reactions were
      encountered. A high dose of CPT-11 induced apoptotic cell death mediated by
      caspase cascade, whereas a low dose of CPT-11 induced irreversible cell
      morphological changes. The cell shape of the transformed PC12 cells was similar
      to fibroblasts, and these were termed FLTP12 (fibroblast-like transformed PC12).
      FLTP12 cells showed some differences from the original PC12 cells. In addition,
      cultured media of passed FLTP12 cells induced same cell transformation in PC12
      cells. To examine how this transformation may be triggered, the possible
      involvement of a growth factor(s) was investigated. Among those tested, the
      possible involvement of basic fibroblast growth factor (basic-FGF) was observed,
      whereas basic FGF antibody did not affect the induction of cell transformation.
      Molecular sieve analysis revealed that transformation-inducing factor is large
      molecule protein like cell attachment factors (>100K), and we demonstrated the
      direct involvement of tenascin in the transformation of PC12 cell.

PMID- 10906441
TI  - In vitro cytotoxicity tests on cultured human skin fibroblasts to predict skin
      irritation potential of surfactants.
AB  - Cultured human skin cells are a potentially useful model for skin irritancy
      testing. We have investigated the use of human skin fibroblasts for in vitro
      screening for skin toxicity. To assess the cytotoxic effects of surfactants, cell
      viability was measured by the NRU (neutral red uptake) assay and AB (Alamar blue)
      assay as in vitro methods. The skin irritation potential of surfactants by human
      skin patch test was assessed as in vivo methods. The close relationship was found
      between AB assay with human skin fibroblasts and human patch test (r=0.867).
      There was a relatively good agreement between the NRU and in vivo patch test
      (r=0.648). These results suggest that AB and NRU assay using cultured human
      fibroblast could be predictable methods for the irritancy of various surfactants
      in human.

PMID- 10906442
TI  - Investigation of induced changes in interleukin 1beta mRNA expression by cultured
      human dendritic cells as an in vitro approach to skin sensitization testing.
AB  - It has been reported previously that in vitro treatment of human blood derived
      dendritic cells (DC) with contact allergens provokes the elevated expression of
      mRNA for interleukin (IL) 1beta, under conditions where similar treatment of
      cells with the non-sensitizing skin irritant sodium lauryl sulfate (SLS) did not
      alter IL-1beta mRNA levels (Reutter et al., 1997). The purpose of the present
      investigation was to evaluate further this phenomenon and to explore the
      potential utility of this approach for the purpose of skin sensitization testing.
      Human peripheral blood progenitor cells prepared from healthy adult volunteers
      were cultured in the presence of IL-4 and granulocyte/macrophage colony
      stimulating factor. After 5 days of culture, the majority of cells had a
      Langerhans cell-like phenotype, with characteristic dendritic morphology and cell
      surface expression of CD83, major histocompatibility complex class II and CD1a
      determinants. These blood-derived DC were cultured in the presence of the contact
      allergen 2,4-dinitrofluorobenzene (DNFB), SLS or vehicle alone and mRNA
      expression for IL-1beta, IL-6 and IL-18 was analysed by semiquantitative reverse
      transcriptase polymerase chain reaction. Constitutive expression of all three
      cytokines was observed for DC isolated from all donors examined. Exposure to DNFB
      resulted in upregulation of IL-1beta mRNA (two- to threefold) in cells derived
      from three out of eight donors whereas IL-6 and IL-18 were largely unaffected by
      allergen exposure. In contrast, SLS treatment did not induce IL-1beta mRNA
      expression in any of the donors investigated. Analysis of cytokine mRNA
      expression using the protocol described by Reutter et al. (1997), did not
      increase the sensitivity of measurement of induced cytokine expression. Although
      selected upregulation of IL-1beta by blood derived DC has been confirmed, a wider
      range of contact allergens and irritants need to be assessed before this approach
      could be considered for hazard identification.

PMID- 10906444
TI  - Corneal opacity, hydration and endothelial morphology in the bovine cornea
      opacity and permeability assay using reduced treatment times.
AB  - The purpose of this study was to determine whether the standard bovine cornea
      opacity and permeability (BCOP) assay exposure time of 10 minutes overestimates
      the ocular irritancy of chemical substances. Corneas were subjected to BCOP
      protocol following 30-second and 1-minute exposures to irritants. Corneal opacity
      and hydration (mg H(2)O/mg cornea) were then measured and compared to data
      obtained after 10 minute irritant treatments. For most test substances corneal
      opacity and hydration were lower following reduced exposure times. It is
      suggested that using shorter exposure times in BCOP protocol may be more
      predictive of human response to ocular irritants, since irritants are usually in
      brief contact with the ocular surface during accidental exposure. A second
      purpose of this study was to examine effects of irritants on the corneal
      endothelium. Corneas were treated according to BCOP protocol following exposure
      to irritants for 1 or 10 minutes. The endothelium was stained with Alizarin Red
      and trypan blue, and examined using light microscopy. Severe irritants, such as
      NaOH and trichloroacetic acid, cause endothelial cell death. It was also
      determined that simply mounting the cornea in the BCOP assay holders caused
      damage to 20% of the endothelial cells. Because the endothelium is essential for
      normal corneal transparency and hydration, it is suggested that examination of
      the endothelium be added to the BCOP assay and that optimization of the assay
      will require modification of the cornea holders.

PMID- 10906443
TI  - Isolated hepatocytes of rainbow trout (Oncorhynchus mykiss) as a tool to
      discriminate between differently contaminated small river systems.
AB  - Isolated hepatocytes of rainbow trout (Oncorhynchus mykiss) were exposed to
      native waters and acetone sediment extracts of Krahenbach and Korsch, two small
      rivers in south-west Germany with different levels of chemical contamination, and
      were investigated by means of electron microscopic and enzyme biochemical
      techniques to evaluate sublethal cytotoxic effects. Between both rivers as well
      as between free water phase and sediment, significant differences in the toxic
      burden could be detected. Results document that dilutions of Krahenbach and
      Korsch surface water and sediment extracts induce time- and dose-dependent
      morphological and biochemical changes. Especially in water and sediments of the
      river Korsch, strong contamination could be observed. After exposure to samples
      from the Korsch, both morphological and biochemical responses of isolated
      hepatocytes were more prominent than following exposure to samples of Krahenbach,
      thus reflecting the different chemical burden of the two river systems.
      Cytopathological effects also included deformation of nuclear envelopes and
      increase of heterochromatin, heterogeneity of mitochondria, vesiculation of
      cisternae of the rough endoplasmic reticulum, as well as proliferation of the
      smooth endoplasmic reticulum. Moreover, peroxisomal and lysosomal proliferation
      could be correlated to a stimulation of the corresponding marker enzymes,
      catalase and acid phosphatase. In both rivers, activities of lactate
      dehydrogenase and alanine aminotransferase as markers of cytosolic glycolysis and
      protein metabolism were increased indicating a general stimulation of cellular
      metabolism. Cytological changes in isolated hepatocytes thus not only serve to
      discriminate between different levels of contamination of water, but may also
      help to differentiate between pollution levels of sediments.

PMID- 10906445
TI  - The use of structure-activity relationships and markers of cell toxicity to
      detect non-genotoxic carcinogens.
AB  - In contrast to the situation for genotoxic carcinogens, few in vitro tests exist
      that can detect early markers of the events thought to be associated with non
      genotoxic carcinogenesis. Also, comparatively little is known about the
      quantitative structure-activity relationships (Q)SARs of these agents. This
      review discusses published SAR studies conducted on non-genotoxic carcinogens, in
      relation to the use of several markers of in vitro cell toxicity (inhibition of
      gap-junctional intercellular communication, inhibition of tubulin polymerization,
      modulation of apoptosis and induction of cell proliferation), which are used as
      endpoints for screening this class of carcinogen. Much of the work has involved
      the identification of new biophores (substructural features of molecules
      associated with toxicity), as well as other structural features, which are
      thought to predispose the chemicals to ligand binding with specific target
      molecules acting as possible receptors (e.g. protein kinase C, the oestrogen,
      peroxisome-proliferator and tubulin protein receptors), implicated in the
      mechanism of toxicity involved. It is concluded that (a) there is an urgent need
      for more information on (Q)SARs for non-genotoxic carcinogens; (b) this
      information should be acquired by using several different approaches in a variety
      of laboratories; and (c) such research should proceed together with more studies
      on the mechanisms of cell toxicity caused by these chemicals, including the
      identification and characterisation of further specific receptors involved in
      mediating the various types of cell toxicity associated with this type of
      carcinogenesis.

PMID- 10906446
TI  - Role of the extracellular matrix during neural crest cell migration.
AB  - Once specified to become neural crest (NC), cells occupying the dorsal portion of
      the neural tube disrupt their cadherin-mediated cell-cell contacts, acquire
      motile properties, and embark upon an extensive migration through the embryo to
      reach their ultimate phenotype-specific sites. The understanding of how this
      movement is regulated is still rather fragmentary due to the complexity of the
      cellular and molecular interactions involved. An additional intricate aspect of
      the regulation of NC cell movement is that the timings, modes and patterns of NC
      cell migration are intimately associated with the concomitant phenotypic
      diversification that cells undergo during their migratory phase and the fact that
      these changes modulate the way that moving cells interact with their
      microenvironment. To date, two interplaying mechanisms appear central for the
      guidance of the migrating NC cells through the embryo: one involves secreted
      signalling molecules acting through their cognate protein kinase/phosphatase-type
      receptors and the other is contributed by the multivalent interactions of the
      cells with their surrounding extracellular matrix (ECM). The latter ones seem
      fundamental in light of the central morphogenetic role played by the
      intracellular signals transduced through the cytoskeleton upon integrin ligation,
      and the convergence of these signalling cascades with those triggered by
      cadherins, survival/growth factor receptors, gap junctional communications, and
      stretch-activated calcium channels. The elucidation of the importance of the ECM
      during NC cell movement is presently favoured by the augmenting knowledge about
      the macromolecular structure of the specific ECM assembled during NC development
      and the functional assaying of its individual constituents via molecular and
      genetic manipulations. Collectively, these data propose that NC cell migration
      may be governed by time- and space-dependent alterations in the expression of
      inhibitory ECM components; the relative ratio of permissive versus non-permissive
      ECM components; and the supramolecular assembly of permissive ECM components. Six
      multidomain ECM constituents encoded by a corresponding number of genes appear to
      date the master ECM molecules in the control of NC cell movement. These are
      fibronectin, laminin isoforms 1 and 8, aggrecan, and PG-M/version isoforms V0 and
      V1. This review revisits a number of original observations in amphibian and avian
      embryos and discusses them in light of more recent experimental data to explain
      how the interaction of moving NC cells with these ECM components may be
      coordinated to guide cells toward their final sites during the process of
      organogenesis.

PMID- 10906447
TI  - Distinct regulatory elements direct delta1 expression in the nervous system and
      paraxial mesoderm of transgenic mice.
AB  - The Delta1 gene encodes one of the Notch ligands in mice. Delta1 is expressed
      during early embryogenesis in a complex and dynamic pattern in the paraxial
      mesoderm and neuroectoderm, and is essential for normal somitogenesis and
      neuronal differentiation. Molecular components thought to act in response to
      ligand binding and Notch activation have been identified in different species. In
      contrast, little is known about the transcriptional regulation of Notch receptors
      and their ligands. As a first step to identify upstream factors regulating Delta1
      expression in different tissues, we searched for cis-regulatory regions in the
      Delta1 promoter able to direct heterologous gene expression in a tissue specific
      manner in transgenic mice. Our results show that a 4.3 kb genomic DNA fragment of
      the Delta1 gene is sufficient in a lacZ reporter transgene to reproduce most
      aspects of Delta1 expression from the primitive streak stage to early
      organogenesis. Using a minimal Delta1 promoter we also show that this upstream
      region contains distinct regulatory modules that individually direct tissue
      specific transgene expression in subdomains of the endogenous expression pattern.
      It appears that expression in the paraxial mesoderm depends on the interaction of
      multiple positive and negative regulatory elements. We also find that at least
      some regulatory sequences required for transgene expression in subdomains of the
      neural tube have been maintained during the evolution of mammals and teleost
      fish, suggesting that part of the regulatory network that controls expression of
      Delta genes may be conserved.

PMID- 10906448
TI  - The mouse rib-vertebrae mutation disrupts anterior-posterior somite patterning
      and genetically interacts with a Delta1 null allele.
AB  - Rib-vertebrae (rv) is an autosomal recessive mutation in mouse that affects the
      morphogenesis of the vertebral column. Axial skeleton defects vary along the
      anterior-posterior body axis, and include split vertebrae and neural arches, and
      fusions of adjacent segments. Here, we show that defective somite patterning
      underlies the vertebral malformations and altered Notch signaling may contribute
      to the phenotype. Somites in affected regions are irregular in size and shape,
      epithelial morphology is disrupted, and anterior-posterior somite patterning is
      abnormal, reminiscent of somite defects obtained in loss-of-function alleles of
      Notch signaling pathway components. Expression of Dll1, Dll3, Lfng and Notch1 is
      altered in rv mutant embryos, and rv and Dll1(lacZ), a null allele of the Notch
      ligand Delta1, genetically interact. Mice double heterozygous for rv and
      Dll1(lacZ), show vertebral defects, and one copy of Dll1(lacZ) on the homozygous
      rv background enhances the mutant phenotype and is lethal in the majority of
      cases. However, fine genetic mapping places rv into an interval on chromosome
      seven that does not contain a gene encoding a known component of the Notch
      signaling pathway.

PMID- 10906449
TI  - The longitudinal visceral musculature of Drosophila melanogaster persists through
      metamorphosis.
AB  - The larval gut of Drosophila is coated with visceral muscles of mesodermal
      origin. In the midgut region this musculature comprises circular and longitudinal
      fibres. The complete visceral musculature is described to be removed during
      metamorphosis and to be replaced by a newly differentiated imaginal tissue
      resembling the morphology of the larval musculature. However, progenitors of this
      imaginal visceral musculature have never been detected prior to differentiation.
      Here I present results indicating that the longitudinal visceral musculature of
      the midgut completely persists through metamorphosis. Single cells expressing
      green fluorescent protein (GFP) as a marker were transplanted at the blastoderm
      stage. All clones contributing to the longitudinal visceral musculature detected
      in third instar larvae were recovered after metamorphosis in adult flies. Further
      evidence for the persistence of the larval visceral musculature was obtained from
      the P[Gal4] insertion line 5053A. It expresses GAL4 specifically in the
      longitudinal visceral muscles of the midgut of all developmental stages to the
      adult fly beginning at the end of embryogenesis. By using GFP as a reporter, it
      was possible to follow these cells through the entire metamorphosis. Although the
      muscles undergo dramatic morphological changes including the loss of their
      contractile system, no evidence for a replacement of the larval visceral
      musculature by imaginal precursor cells was detected.

PMID- 10906450
TI  - Involvement of fibroblast growth factor (FGF)18-FGF8 signaling in specification
      of left-right asymmetry and brain and limb development of the chick embryo.
AB  - To elucidate roles of fibroblast growth factors (FGF)18 during vertebrate
      development, we examined expression patterns of Fgf18 in chick embryos and
      observed effects of FGF18 protein on the Hensen's node, isthmus, and limb buds.
      Fgf18 is expressed on the right side of the node before the expression of Fgf8
      starts. FGF18 protein can induce expression of Fgf8 on the left side of the node,
      indicating involvement of both FGFs in specification of left-right asymmetry. In
      the developing brain, Fgf18 is expressed in the isthmus, following the Fgf8
      expression. Since Fgf18 is induced ectopically during formation of the second
      midbrain by FGF8 protein, both FGFs also elaborate midbrain development. In the
      limb bud, Fgf18 is expressed in the mesenchyme and ectopic application of FGF18
      protein inhibits bone growth in the limb. FGF18 is thus likely an endogenous
      ligand of FGF receptor 3, whose mutation causes bone dysplasia in humans. These
      results demonstrate that the FGF18-FGF8 signaling is involved in various
      organizing activities and the signaling hierarchies between FGF18 and FGF8 seem
      to change during patterning of different structures.

PMID- 10906451
TI  - Unique and redundant functions of SR proteins, a conserved family of splicing
      factors, in Caenorhabditis elegans development.
AB  - Serine/arginine-rich proteins (SR proteins) constitute a family of RNA-binding
      proteins conserved throughout metazoans. The SR proteins are essential for
      constitutive pre-mRNA splicing and also affect regulated pre-mRNA splicing. We
      identified five putative genes encoding SR proteins (referred to as srp genes) in
      Caenorhabditis elegans, examined their expression using the gfp gene as a
      reporter, and suppressed their functions by double-stranded RNA-mediated
      interference (RNAi). The srp::gfp fusion genes were expressed in the nuclei of
      most somatic cells and showed no obvious tissue- or stage-specific expression.
      Simultaneous RNAi of the five srp genes resulted in embryonic lethality, whereas
      RNAi of individual srp genes caused no obvious morphological abnormality in the
      F1 progeny, indicating functional redundancy of the SR proteins. However, RNAi of
      several combinations of srp genes caused various developmental abnormalities,
      such as abnormal somatic gonad structures, delayed shift of the germ cell sexual
      differentiation, and abnormal spermatogenesis. Our results suggest that
      individual SR proteins have unique but somewhat redundant functions in C. elegans
      development.

PMID- 10906452
TI  - The developmental potentials of the caudalmost part of the neural crest are
      restricted to melanocytes and glia.
AB  - The avian spinal cord is characterized by an absence of motor nerves and sensory
      nerves and ganglia at its caudalmost part. Since peripheral sensory neurons
      derive from neural crest cells, three basic mechanisms could account for this
      feature: (i) the caudalmost neural tube does not generate any neural crest cells;
      (ii) neural crest cells originating from the caudal part of the neural tube
      cannot give rise to dorsal root ganglia or (iii) the caudal environment is not
      permissive for the formation of dorsal root ganglia. To solve this problem, we
      have first studied the pattern of expression of ventral (HNF3beta) and dorsal
      (slug) marker genes in the caudal region of the neural tube; in a second
      approach, we have recorded the emergence of neural crest cells using the HNK1
      monoclonal antibody; and finally, we have analyzed the developmental potentials
      of neural crest cells arising from the caudalmost part of the neural tube in
      avian embryo in in vitro culture and by means of heterotopic transplantations in
      vivo. We show here that neural crest cells arising from the neural tube located
      at the level of somites 47-53 can differentiate both in vitro and in vivo into
      melanocytes and Schwann cells but not into neurons. Furthermore, the neural tube
      located caudally to the last pair of somites (i.e. the 53rd pair) does not give
      rise to neural crest cells in any of the situations tested. The specific
      anatomical aspect of the avian spinal cord can thus be accounted for by limited
      developmental potentials of neural crest cells arising from the most caudal part
      of the neural tube.

PMID- 10906453
TI  - polyhomeotic controls engrailed expression and the hedgehog signaling pathway in
      imaginal discs.
AB  - Polycomb group (PcG) genes maintain cell identities during development in insects
      and mammals and their products are required in many developmental pathways. These
      include limb morphogenesis in Drosophila melanogaster, since PcG genes interact
      with identity and pattern specifying genes in imaginal discs and clones of
      polyhomeotic (ph) null cells induce abnormal limb patterning. Such clones are
      associated with ectopic expression of engrailed, hedgehog, patched, cubitus
      interruptus and decapentaplegic, in a compartment specific manner. Our results
      also reveal negative engrailed regulation by ph in both disc compartments: ph
      silences engrailed in anterior cells and maintains the level of engrailed
      expression in posterior ones. We suggest that PcG targets are not exclusively
      regulated by an on/off mechanism, but that the PcG also exerts negative
      transcriptional control on active genes.

PMID- 10906454
TI  - Expression and regulation of chicken fibroblast growth factor homologous factor
      (FHF)-4 at the base of the developing limbs.
AB  - Fibroblast growth factor homologous factors (FHFs) have been implicated in limb
      and nervous system development. In this paper we describe the expression of the
      cFHF-4 gene during early chicken development. cFHF-4 is expressed in the paraxial
      mesoderm, lateral ridge, and, most prominently, in the posterior-dorsal side of
      the base of each limb bud. The expression pattern of cFHF-4 at the base of the
      limbs is not altered by tissue grafts containing the zone of polarizing activity
      (ZPA), by implants of Shh-expressing cells, or by implants of beads containing
      retinoic acid, nor does it depend on the distal growth of the limb as it is not
      altered in limb buds that are surgically truncated. In three chicken mutants
      affecting limb patterning - talpid(2), limbless, and wingless - altered patterns
      of cFHF-4 expression are correlated with abnormal nerve plexus formation and
      altered patterns of limb bud innervation. Similarly, ectopic expression of cFHF-4
      is correlated with a local induction of limb-like innervation patterns when beads
      containing FGF-2 are implanted in the flank. In these experiments, both ectopic
      innervation and ectopic expression of cFHF-4 in the flank were observed
      regardless of the size of the FGF-2-induced outgrowths. By contrast, ectopic
      expression of Shh and HoxD13 are seen only in the larger FGF-2-induced
      outgrowths. Taken together, these data suggest that cFHF-4 regulates or is
      coregulated with early events related to innervation at the base of the limbs.

PMID- 10906455
TI  - semang affects the development of a subset of cells in the Drosophila compound
      eye.
AB  - semang (sag), a mutation isolated as a suppressor of Drosophila Src42A, has
      previously been shown to affect some receptor tyrosine kinase mediated embryonic
      processes. Here we show that sag specifically affects the development of R1, R6
      and R7 photoreceptor cells in a cell-autonomous manner. These cells are absent in
      the mutant at the time when they normally appear in the ommatidial pre-clusters.
      Genetic analyses suggest that sag functions downstream of, or parallel to, Mapk
      and Yan in the photoreceptor differentiation pathway. The autonomous requirement
      of sag for R1/R6/R7 development could be explained by a selective impairment of
      the late, but not early, rounds of Egfr-induced precursor cell assembly by the
      sag mutations. Egfr signaling is highly regulated by autocrine or paracrine
      mechanisms in different cells. Knowing that the photoreceptor cluster formation
      is a complex process involving dynamic changes in cell-cell contact, our
      hypothesis is that the sag alleles affected certain special aspects of Egfr
      signaling that are unique for the recruitment of R1/R6/R7 cells.

PMID- 10906456
TI  - Endothelial monocyte activating polypeptide II inhibits lung neovascularization
      and airway epithelial morphogenesis.
AB  - Neovascularization is crucial to lung development and is mediated through a
      variety of angiogenic and anti-angiogenic factors. Herein, we show that excess
      Endothelial Monocyte Activating Polypeptide (EMAP) II, an anti-angiogenic
      protein, not only inhibits fetal lung neovascularization, but also significantly
      alters airway epithelial morphogenesis. In a murine allograft model of lung
      neovascularization and morphogenesis, embryonic lungs transplanted under the skin
      of immunocompromised mice receiving intraperitoneal EMAP II, had a 56% reduction
      in vessel density (P<0.0001) compared to control. EMAP II treated lung
      transplants also exhibited a marked alteration in lung morphogenesis, including
      lack of type II alveolar cell formation, determined by markedly decreased
      expression of surfactant protein C, and increased apoptosis. In contrast, lung
      implants in animals receiving an EMAP II blocking antibody had an increase in
      vessel density of 50% (P<0.0001) and increased expression of surfactant protein C
      mRNA in distal epithelium. These studies demonstrate that EMAP II negatively
      modulates lung neovascularization as well as leading to the arrest of lung airway
      epithelial morphogenesis and apoptosis.

PMID- 10906457
TI  - Extensive brain hemorrhage and embryonic lethality in a mouse null mutant of CREB
      binding protein.
AB  - CREB-binding protein (CBP) is a transcriptional co-activator which is required by
      many transcription factors. Rubinstein-Taybi syndrome (RTS), which is an
      autosomal dominant syndrome characterized by abnormal pattern formation, is
      associated with mutations in the human CBP gene. Various abnormalities occur at
      high frequency in the skeletal system of heterozygous Cbp-deficient mice, but
      some features of RTS such as cardiac anomalies do not, suggesting that some
      symptoms of RTS are caused by a dominant-negative mechanism. Here we report the
      characterization of homozygous Cbp-deficient mice. Homozygous mutants died around
      E10.5-E12.5, apparently as a result of massive hemorrhage caused by defective
      blood vessel formation in the central nervous system, and exhibited apparent
      developmental retardation as well as delays in both primitive and definitive
      hematopoiesis. Cbp-deficient embryos exhibited defective neural tube closure
      which was similar to those observed in twist-deficient embryos. However, a
      decrease in the level of twist expression was not observed in Cbp-deficient
      embryos. Anomalous heart formation, a feature of RTS patients and mice mutated in
      the CBP-related molecule, p300, was not observed in Cbp-deficient embryos. Since
      both Cbp and p300 are ubiquitously expressed in embryonic tissues including the
      developing heart, these results suggest that cardiac anomalies observed in RTS
      patients may be caused by a dominant negative effect of mutant CBP.

PMID- 10906458
TI  - Ectopic expression of c-ski disrupts gastrulation and neural patterning in
      zebrafish.
AB  - The c-ski proto-oncogene encodes a transcriptional regulator that has been
      implicated in the development of different tissues at different times during
      vertebrate development. We identified two novel paralogues of the c-ski gene
      family, skiA and skiB in zebrafish (Danio rerio). The skiA protein is maternal
      and ubiquitous while skiB is zygotic. Overexpression of SkiA or SkiB disrupted
      gastrulation and resulted in a dorsalized phenotype. In situ analyses suggested
      that overexpression of Ski leads to a slight expansion of dorsal-axial mesoderm,
      diminishment or loss of ventral mesoderm and radialization of dorsal
      neuroectoderm. The dorsalized phenotype could be rescued by the ventral
      specifying factor, BMP4. These results provide evidence that Ski proteins
      participate in dorsal-ventral specification of both neuroectoderm and mesoderm.

PMID- 10906459
TI  - Targeted disruption of the Nkx3.1 gene in mice results in morphogenetic defects
      of minor salivary glands: parallels to glandular duct morphogenesis in prostate.
AB  - To investigate functions of the homeodomain-containing transcription factor
      Nkx3.1 a null mutation was generated by targeted gene disruption introducing the
      bacterial LacZ gene as reporter into the locus. In addition to defects in duct
      morphogenesis of the prostate and bulbourethral gland displaying progressive
      epithelial hyperplasia and reduced ductal branching (Bhatia-Gaur, R., Donjacour,
      A.A., Sciavolino, P.J., Kim, M., Desai, N., Young, P., Norton, C.R., Gridley, T.,
      Cardiff, R.D., Cunha, G.R., Abate-Shen, C., Shen, M.M., 1999. Genes Dev. 13, 966
      977), we observed a novel phenotype in minor salivary glands of Nkx3.1 null
      mutants. Minor salivary glands in the oral cavity of mutant mice appeared reduced
      in size and exhibited severely altered duct morphology. Other Nkx3.1 expressing
      regions were unaffected by the mutation. The activity of the Nkx3. 1/LacZ allele
      faithfully reflected the known expression domains of Nkx3.1 in sclerotome, a
      subset of blood vessels, Rathke's pouch, and ductal epithelium in prostate and
      minor salivary glands during pre- and postnatal mouse development. However, it
      was additionally expressed in the heart, duodenum and lung. These ectopic
      expression domains resemble the pattern of the Nkx2.6 gene which is closely
      linked to Nkx3.1 in the mouse genome and its regulation may therefore be affected
      by the mutation. In Nkx3.1/Shh compound mutant mice we found that Nkx3.1
      expression in sclerotome and prostate was strictly dependent on sonic hedgehog
      (Shh) signaling, while other expression domains including heart and gut were
      independent of Shh. Expression in lung appeared augmented in the absence of Shh.
      Our results suggest that Nkx3.1 plays a unique role in regulating proliferation
      of glandular epithelium and in the formation of ducts in prostate and minor
      salivary glands.

PMID- 10906460
TI  - Ectopic Sox3 activity elicits sensory placode formation.
AB  - The induction of sensory organ placodes, in particular the lens placode,
      represents the paradigm for induction. We show that medaka Sox3 is expressed in
      the neuroectoderm and in the placodes of all sensory organs prior to placode
      formation and subsequently in placode-derived tissues. Ectopic Sox3 expression
      leads to ectopic expression of Pax6 and Eya1 in embryonic ectoderm and causes
      ectopic lens and otic vesicle formation. The descendants of cells ectopically
      expressing Sox3-mRNA contribute to ectopic lens tissue. This suggests a
      permissive role for Sox3 in establishing a placodal competence. In addition,
      ectopic Sox3 expression leads to the dysgenesis of the endogenous sensory organs.
      Both effects of ectopic Sox3 expression can be separated by ectopic expression of
      a truncated Sox3 variant depending on its expression level. Our data suggests
      that Sox3 is a permissive factor for sensory placode formation and plays an
      important role in sensory organ development.

PMID- 10906461
TI  - Parathyroid hormone-related peptide is involved in protection against invasion of
      tooth germs by bone via promoting the differentiation of osteoclasts during tooth
      development.
AB  - In order to elucidate the role of parathyroid hormone-related peptide (PTHrP) in
      tooth development, we treated tooth germ explants of mouse molars with antisense
      phosphorothioate-oligodeoxynucleotide (ODN) against PTHrP. Antisense ODN
      treatment of the explants resulted in the invasion of the tooth germs by bone.
      The number of tartrate-resistant acid phosphatase (TRAP)-positive cells around
      the tooth germs in antisense ODN-treated explants was much lower than that of the
      control explants. Electron microscopic examination suggested that the antisense
      ODN-treatment inhibited differentiation of osteoclasts. Treatment of the explants
      with bisphosphonate or vitamin K2, inhibitors of the differentiation of
      osteoclasts, induced the invasion by bone into the tooth germs as observed in the
      antisense ODN-treated explants. The results obtained suggest that PTHrP is
      involved in the mechanism protecting tooth germs from bone invasion by promoting
      the differentiation of osteoclasts around them.

PMID- 10906462
TI  - Identification of maverick, a novel member of the TGF-beta superfamily in
      Drosophila.
AB  - The transforming growth factor-beta (TGF-beta) superfamily of structurally
      related ligands regulates essential signaling pathways that control many aspects
      of cell behavior in organisms across the phylogenetic spectrum. Here we report
      the identification of maverick (mav), a gene that encodes a new member of the TGF
      beta superfamily in Drosophila. Phylogenetic analysis and sequence comparison
      suggest that Mav cannot be easily assigned to any one sub-family, since it is
      equally related to BMP, activin and TGF-beta ligands. mav maps to the fourth
      chromosome and is expressed throughout development. In situ hybridization
      experiments reveal the presence of maternally derived mav transcript in
      precellular blastoderm embryos. Later in development, mav is expressed in a
      dynamic pattern in the developing gut, both in endodermal and visceral mesodermal
      cells. In adult females, high levels of mav mRNA are present in late stage egg
      chambers.

PMID- 10906463
TI  - Transforming growth factor-beta5 expression during early development of Xenopus
      laevis.
AB  - Members of the transforming growth factor-beta (TGF-beta) superfamily play
      various roles during development in both vertebrates and invertebrates. Two
      isoforms, TGF-beta2 and -beta5, have been isolated from Xenopus laevis. We
      describe here the localization of TGF-beta5 mRNA in early embryos of X. laevis,
      assessed by whole-mount in situ hybridization. The first detectable expression of
      TGF-beta5 was seen in the stage 14 embryo at the posterior tip of notochord,
      which continued to later stages, accompanied by the expression in bilateral
      regions of posterior wall in the tail region next to the notochord. At later
      stages, transient expression was seen in the cement gland (around stage 21) and
      in the somites (stages 24-27). In addition, expression was present in the
      branchial arches (stage 29-36) and olfactory placodes (stage 36).

PMID- 10906464
TI  - RhoB is expressed in migrating neural crest and endocardial cushions of the
      developing mouse embryo.
AB  - RhoB mRNA expression was examined in the developing mouse embryo between E8.5 and
      E11.5. Specific expression was found in migrating neural crest (NC) cells, from
      the first stages of their migration at E9.5, throughout the migration period.
      Expression is maintained in NC derivatives for at least one embryonic day after
      they reach their final destinations, but is then down-regulated. RhoB is also
      expressed in non NC-derived neural tissues, including motor neurones and the
      floor plate of the neural tube. RhoB mRNA expression is also found in the
      developing endocardial cushions of the atrioventricular and outflow regions of
      the developing heart.

PMID- 10906466
TI  - Cloning and expression of the sponge longevity gene SDLAGL.
AB  - Porifera show a characteristic Bauplan in spite of the fact that (almost) all
      cells are telomerase-positive and presumably provided with an unlimited potency
      for cell proliferation. One gene, SDLAGL, was identified in the marine sponge
      Suberites domuncula whose deduced polypeptide showed high sequence similarity to
      the longevity assurance genes from other Metazoa. While in single cells no
      transcripts of SDLAGL could be identified, high expression was seen after re
      aggregation of single cells and in proliferating cells of primmorphs.

PMID- 10906465
TI  - The putative Drosophila methyltransferase gene dDnmt2 is contained in a
      transposon-like element and is expressed specifically in ovaries.
AB  - Several organisms, including Drosophila melanogaster, are apparently devoid of
      DNA methylation. This might reflect a highly restricted activity of DNA
      methyltransferases, a loss of methyltransferase activity during evolution or the
      dispensability of DNA methylation due to an efficient substitute mechanism.
      Vestiges of a Drosophila DNA methylation system have been identified recently. We
      show here that the putative DNA methyltransferase gene, dDnmt2, is the component
      of a transposon-like element. This element also contains a second, novel open
      reading frame with homologies to a yeast protein involved in RNA processing. Both
      open reading frames are coordinately expressed and transcripts are present
      specifically in ovarian nurse cells as well as during early stages of embryonic
      development.

PMID- 10906467
TI  - Expression of DM-GRASP/BEN in the developing mouse spinal cord and various
      epithelia.
AB  - The expression pattern of the immunoglobulin DM-GRASP/BEN gene was studied in the
      mouse embryo using in situ hybridization. DM-GRASP/BEN is expressed in the spinal
      cord in a subset of motoneurons expressing Islet-1, and non homogeneously in the
      dorsal root ganglia (DRG). In contrast, it's expression is homogeneous in the
      vestibulo-cochlear and trigemminal ganglia. DM-GRASP/BEN is also expressed in
      various epithelia of ectodermal or endodermal origin like the nasal,
      buccopharyngal and lung epithelia. In upper lip, DM-GRASP/BEN transcripts are
      present in the epidermal cells of the developing hair vibrissa follicles. First
      detected in the hair placode, DM-GRASP/BEN expression is localized in the central
      cells of the epithelial hair peg and then in a thin layer of cells crushed
      against the outer root sheath by the outgrowth of the hair shaft.

PMID- 10906468
TI  - Pax2, Otx2, Gbx2 and Fgf8 expression in early otic vesicle development.
AB  - The inner ear is a suitable system to study the mechanisms involved in the
      specification of different functional domains during morphogenesis. Using single
      and double in situ hybridization (ISH) we show that three transcription factors
      (Otx2, Gbx2and Pax2) and a member of the fibroblast growth factor family (Fgf8)
      could participate in the compartmentalization of the otic vesicle and in the
      formation of the acoustic-vestibular ganglion.

PMID- 10906469
TI  - Conservation of sequence and expression of Xenopus and zebrafish dHAND during
      cardiac, branchial arch and lateral mesoderm development.
AB  - dHAND and eHAND are related basic helix-loop-helix transcription factors that are
      expressed in the cardiac mesoderm and in numerous neural crest-derived cell types
      in chick and mouse. To better understand the evolutionary development of
      overlapping expression and function of the HAND genes during embryogenesis, we
      cloned the zebrafish and Xenopus orthologues. Comparison of dHAND sequences in
      zebrafish, Xenopus, chick, mouse and human demonstrated conservation throughout
      the protein. Expression of dHAND in zebrafish was seen in the earliest precursors
      of all lateral mesoderm at early gastrulation stages. At neurula and later
      stages, dHAND expression was observed in lateral precardiac mesoderm, branchial
      arch neural crest derivatives and posterior lateral mesoderm. At looping heart
      stages, cardiac dHAND expression remained generalized with no apparent
      regionalization. Interestingly, no eHAND orthologue was found in zebrafish. In
      Xenopus, dHAND and eHAND were co-expressed in the cardiac mesoderm without the
      segmental restriction seen in mice. Xenopus dHAND and eHAND were also expressed
      bilaterally in the lateral mesoderm without any left-right asymmetry. Within the
      branchial arches, XdHAND was expressed in a broader domain than XeHAND, similar
      to their mouse counterparts. Together, these data demonstrate conservation of
      HAND structure and expression across species.

PMID- 10906471
TI  - Structure and expression of Xenopus karyopherin-beta3: definition of a novel
      synexpression group related to ribosome biogenesis.
AB  - Karyopherin-beta3 is a nuclear transport receptor that appears to be involved in
      nuclear import of ribosomal proteins. Here we report on sequence and expression
      of karyopherin-beta3 in Xenopus. The differential distribution of karyopherin
      beta3 mRNA during Xenopus embryogenesis is similar to that of several other
      protein import factors and of ribosomal proteins. These genes thus define a novel
      synexpression group in the context of ribosome biogenesis.

PMID- 10906470
TI  - erg gene(s) expression during development of the nervous and muscular system of
      quail embryos.
AB  - The expression pattern of K(+) currents is the principal regulator of electrical
      activity during development of the nervous and muscular system. We report here a
      study showing the expression pattern of HERG K(+) currents-encoding (erg) genes
      in various nervous and muscular tissues at different stages of quail embryo
      development.

PMID- 10906472
TI  - Identification of different forms of calpastatin mRNA co-expressed in the
      notochord of Xenopus laevis embryos.
AB  - We isolated three Xenopus cDNA clones, Xcalp1, Xcalp2 and Xcalp3, which encode
      different forms of calpastatin mRNA. Compared to the canonical form of mammalian
      calpastatin, the predicted Xcalp3 protein contained a very long N-terminal domain
      L and an additional inhibitory domain. The other two deduced calpastatin proteins
      were truncated forms, both lacking domain L and containing four (Xcalp2) and two
      (Xcalp1) inhibitory domains, respectively. The presence of Xcalp1, Xcalp2 and
      Xcalp3 transcripts was detected by in situ hybridization in the notochord from
      the embryonic stage 20 to stage 36, afterwards the expression was only present in
      the growing tailbud. As shown by RT-PCR, the three calpastatin mRNAs were also
      expressed in the adult brain.

PMID- 10906473
TI  - tbx20, a new vertebrate T-box gene expressed in the cranial motor neurons and
      developing cardiovascular structures in zebrafish.
AB  - The T-box genes constitute a family of transcriptional regulator genes that have
      been implicated in a variety of developmental processes ranging from the
      formation of germ layers to the regionalization of the central nervous system. In
      this report we describe the cloning and expression pattern of a new T-box gene
      from zebrafish, which we named tbx20. tbx20 is an ortholog of two other T-box
      genes isolated from animals of different phyla - H15 of Drosophila melanogaster
      and tbx-12 of Caenorhabditis elegans, suggesting that the evolutionary origin of
      this gene predates the divergence between the protostomes and deuterostomes.
      During development, tbx20 is expressed in embryonic structures of both mesodermal
      and ectodermal origins, including the heart, cranial motor neurons, and the roof
      of the dorsal aorta.

PMID- 10906474
TI  - Expression patterns of FHL/SLIM family members suggest important functional roles
      in skeletal muscle and cardiovascular system.
AB  - LIM domain containing proteins play critical roles in animal development and
      cellular differentiation. Here, we describe the cloning and expression patterns
      of three members of the four and a half LIM domain-only protein family, FHL1, 2,
      and 3, from mouse. A comparison of embryonic expression patterns of these three
      highly-related genes indicates that they are expressed in an overlapping pattern
      in the developing cardiovascular system, and skeletal muscle. In adult tissues,
      the three genes are expressed in a predominant and overlapping manner in cardiac
      and skeletal muscle. Of the three genes, FHL2 appears to have the most restricted
      expression pattern during development, in heart, blood vessels, and skeletal
      muscle. Expression in heart is highest in cardiac septa and in the region
      adjacent to the atrio-ventricular ring, suggesting a potential role in septation
      or conduction system development. In the heart, FHL1expression was observed
      strongly in developing outflow tract, and to a lesser extent in myocardium. FHL3
      displays low and ubiquitous expression during mouse development. Cardiac
      ventricular expression of FHL1, but not FHL2 or FHL3, was upregulated in two
      mouse models of cardiac hypertrophic and dilated cardiomyopathy. Taken together,
      these data indicate the potential importance of this FHL family in the
      development and maintenance of the cardiovascular system and striated muscle, and
      suggest that FHL1 may play a role in the development of heart disease.

PMID- 10906475
TI  - Expression of nk2.1a during early development of the thyroid gland in zebrafish.
AB  - We show here that a zebrafish orthologue of the Thyroid Transcription Factor-1
      (TTF-1), nk2.1a, is expressed in the developing thyroid gland. Using a fate
      mapping approach we found that an early nk2.1a expression domain in the endoderm
      adjacent to the heart follows morphogenetic movements of the lower jaw, ending up
      in the region in which the mature thyroid gland is located. We therefore suggest
      that nk2.1a labels the thyroid precursor cells from somitogenesis stages onwards.

PMID- 10906476
TI  - Vasa protein expression and localization in the zebrafish.
AB  - Primordial germ cell (PGC) development in the zebrafish is poorly understood. The
      expression of vasa RNA, the only molecular marker so far found to be expressed in
      fish PGCs, suggests its function in the establishment of the germline. The
      protein product of vasa is present throughout the life cycle in the germline of
      Drosophila, Caenorhabditis and Xenopus. The expression pattern of the Vasa
      protein in zebrafish, is still unresolved. We generated an anti-Vasa polyclonal
      antibody and show that it is maternally expressed initially throughout the
      embryo. Interestingly, from the two-cell- to the 1000-cell stage the protein is
      highly concentrated in two 'dots' near the center of the blastomeres and as such
      remains longest detectable in the animal pole blastomeres. The first distinct
      cell-specific expression occurs at 60% epiboly on one side of the blastoderm
      margin. The Vasa protein in the PGCs is organized in a subcellular granular-like
      conformation which is dynamic throughout development.

PMID- 10906477
TI  - Expression of hes6, a new member of the Hairy/Enhancer-of-split family, in mouse
      development.
AB  - Genes of the Hairy/Enhancer-of-split (HES) family encode basic-Helix-Loop-Helix
      proteins that function as nuclear effectors of Notch signaling to regulate the
      transcriptional activity of several Notch target genes. Here, we report the
      characterization of a new member of the HES family, hes6, and describe its
      expression in mouse embryos ranging from 8.5 to 15.5 dpc. High levels of
      expression are observed in several embryonic tissues where Notch signaling is
      known to control cell-fate decisions, like the nervous system, muscle and thymus.
      In the nervous system, hes6 is initially expressed in the closing neural tube and
      then in the spinal cord, cranial and dorsal root ganglia, and brain
      neuroepithelium. During muscle development, the expression of hes6 occurs during
      both myoblast commitment and differentiation, being the first hes gene to reveal
      expression throughout embryonic myogenesis. hes6 is also expressed in epithelial
      cells of the embryonic respiratory, urinary and digestive systems.

PMID- 10906478
TI  - Gdf16, a novel member of the growth/differentiation factor subgroup of the TGF
      beta superfamily, is expressed in the hindbrain and epibranchial placodes.
AB  - We have isolated and characterized the developmental expression of Xenopus gdf16,
      a novel member of the growth/differentiation factor (gdf) gene family. The gdf16
      gene encodes a pre-proprotein of 413 amino acids and a mature peptide of 122
      amino acids. Gdf16 is most closely related to the zebrafish genes dynamo and
      radar, but exhibits a completely different expression pattern. Gene expression is
      detected at early tailbud (stage 25) in the first two epibranchial placodes and
      in a hindbrain-specific domain. As development proceeds, the gene is expressed in
      all the epibranchial placodes, the hindbrain, and the diencephalon.

PMID- 10906480
TI  - DEADSouth is a germ plasm specific DEAD-box RNA helicase in Xenopus related to
      eIF4A.
AB  - DEADSouth was selected in a screen for localized RNAs in Xenopus oocytes. In situ
      hybridization analysis shows that DEADSouth localizes to the vegetal cortex via
      the mitochondrial cloud early in oogenesis and segregates with germ plasm during
      early embryogenesis. These results lend further support for the general concept
      that the role of the early RNA localization pathway in Xenopus is to localize
      germ cell components (reviewed in King, M.L., Zhou, Y., Bubunenko, M. , 1999.
      BioEssays 21, 546-557). Further analysis shows that DEADSouth is a germline
      specific RNA, found exclusively within the germ plasm of oocytes and PGCs, as
      well as in male germ cells. Sequence comparisons with DEADSouth show it to be a
      member of a small sub-family of the DEAD-box RNA-dependent helicases related to
      eIF4A.

PMID- 10906479
TI  - A retinoic acid synthesizing enzyme in ventral retina and telencephalon of the
      embryonic mouse.
AB  - Most retinoic acid (RA) in the embryonic mouse is generated by three
      retinaldehyde dehydrogenases (RALDHs). RALDH1 (also called E1, AHD2 or ALDH1) is
      expressed in the dorsal retina, and RALDH2 (V2, ALDH11) generates most RA in the
      embryonic trunk. The third one, RALDH3 (V1), synthesizes the bulk of RA in the
      head of the early embryo. We show here that RALDH3 is a mouse homologue to ALDH6,
      an aldehyde dehydrogenase cloned from adult human salivary gland (Hsu, L.C.,
      Chang, W.-C., Hiraoka, L., Hsien, C.-L., 1994. Molecular cloning, genomic
      organization, and chromosomal localization of an additional human aldehyde
      dehydrogenase gene, ALDH6. Genomics 24, 333-341), which was recently reported to
      act as a RALDH (Yoshida, A., Rzhetsky, A., Hsu, L.C., Chang, C., 1998. Human
      aldehyde dehydrogenase gene family. Eur. J. Biochem. 251, 549-557). RALDH3
      expression begins in the surface ectoderm over the optic recess. In rapidly
      changing expression patterns it labels the appearance of several ectodermal
      structures: it marks the formation of the lens and the olfactory organ from
      ectodermal placodes, and it delineates the beginning eyelid field. Within the
      optic vesicle, RALDH3 is expressed in the ventral retina and the dorsal pigment
      epithelium. In the telencephalon, RALDH3 is expressed at high levels in the
      lateral part of the ganglionic eminence. From here it extends via the piriform
      cortex into the lower part of the septum. Of the three RALDHs, RALDH3 shows the
      strongest predilection for epithelia.

PMID- 10906481
TI  - Pair-rule genes cooperate to activate en stripe 15 and refine its margins during
      germ band elongation in the D. melanogaster embryo.
AB  - Patterns of gene expression have been well documented during embryogenesis for
      the Drosophila melanogaster trunk segments. The same is not the case for the
      terminal segments. Here, gene expression patterns are followed during
      embryogenesis in the caudal segments (A8-A10 and the anal plate), with special
      attention paid to the novel regulation of engrailed (en). Chosen for this study
      are the pair-rule genes even-skipped (eve), fushi tarazu (ftz), runt (run), hairy
      (h), paired (prd) and odd-skipped (odd), and the segment polarity gene (en). The
      results demonstrate a progressive and coupled translocation of gene expression
      distally for all genes studied, suggesting that the most posterior segments are
      determined later than trunk segments.

PMID- 10906482
TI  - The insect immune protein hemolin is expressed during oogenesis and
      embryogenesis.
AB  - Hemolin is the most abundant bacteria-induced proteins in Hyalophora cecropia
      hemolymph. Its structural features, both at the protein and gene level, ascribe
      this molecule to the immunoglobulin gene superfamily (IgSF) with particular
      homology to neural cell adhesion molecules. An increasing number of evidence
      suggest a role in immune recognition and in cell adhesion events. Hemolin is also
      developmentally regulated as suggested by changes in its concentration during
      larval and pupal ecdysis (Trenczek, T., 1998. Endogenous defense mechanisms of
      insects. Zoology 101, 298-315; Lanz-Mendoza, H., Faye, I., 1999. Physiological
      aspects of the immunoglobulin superfamily in invertebrates. Dev. Comp. Immunol.
      23, 359-374). In the present study the expression of hemolin was investigated in
      oogenesis and in early embryogenesis. Our results reveal that hemolin is
      expressed in follicles and in epidermal and neural tissues of embryos.

PMID- 10906483
TI  - Isolation and expression of a novel member of the CITED family.
AB  - Chicken CITED3 (cCITED3) is a novel gene, which is expressed in the pre-somitic
      mesoderm, the mesonephric tubules, the Wolffian ducts and collecting tubules of
      the developing urogenital system and in the cranial sensory ganglia. Sequence
      analysis revealed that cCITED3 encodes a protein which contains two conserved
      domains that have been described for members of the CITED family.

PMID- 10906484
TI  - Differential patterns of expression of Eps15 and Eps15R during mouse
      embryogenesis.
AB  - Eps15 and Eps15R are related tyrosine kinase substrates, which have been
      implicated in endocytosis and synaptic vesicle recycling. Through the
      protein:protein interaction abilities of their EH domains, they establish a
      complex network of interactions with several proteins, including Numb, a protein
      necessary for neuronal cell fate specification. We analyzed the expression of
      Eps15 and Eps15R during murine development, at the time of active neurogenesis.
      The most striking difference was at the level of subcellular localization, with
      Eps15 present in the cytosol and on the plasma membrane, while Eps15R exhibited
      mainly a nuclear localization. Interesting topographical differences also
      emerged. In the 12.5 days post coitum neuroepithelium, Eps15 was expressed in the
      ventricular zone, which contains proliferating neuroblasts, whereas Eps15R was
      found only in postmitotic neurons. Conversely, both proteins were expressed in
      sensory and cranial ganglia. At later times, the expression of Eps15 and Eps15R
      was widely maintained in neuronal structures. In other tissues, Eps15 was first
      seen in the liver primordium and at low levels in choroid plexus, lung, kidney
      and intestine; later on the expression was maintained at high levels in
      epithelia. Nuclear staining of Eps15R was present in kidney, intestine, lung and
      liver, as well as in heart and pancreas.

PMID- 10906485
TI  - Developmentally regulated expression of the murine ortholog of the potassium
      channel KIR4.2 (KCNJ15).
AB  - The gene KIR4.2 (K(+) inwardly rectifying channel 4.2) has been recently
      identified in the Down syndrome Chromosome Region 1. We have cloned the mouse
      ortholog of KIR4.2 and characterized its expression pattern. In situ
      hybridization showed a restricted and developmentally regulated pattern of
      expression. The expression is starting at E12.5 and expands at E14.5 in different
      tissues and organs, which may be affected in Down syndrome: heart, thymus,
      thyroid gland, and perichondrium. At E17.5, additional epithelia (kidney,
      bladder, stomach, lung) expressed also strongly the gene.

PMID- 10906486
TI  - A physiological method to selectively decrease brain serotonin release.
AB  - In this protocol the effect of both an acute and chronic tryptophan (TRP)-free
      diet on brain serotonin (5-HT) release was studied in rats. Extracellular levels
      of cortical 5-HT, assessed by in vivo microdialysis, revealed a decrease in the
      release of this monoamine. Indeed, 120 min after the acute administration of a
      TRP-free diet, cortical 5-HT release decreased significantly by about 40% with
      respect to a balanced diet and the decrease persisted for more than 6 h. The
      chronic intake of a TRP-free diet induced a gradual reduction in 5-HT release.
      Five days after the diet consumption, our HPLC system detected no 5-HT in
      cortical dialysate. On the contrary, the acute or chronic administration of the
      TRP-free diet made no significant change in extracellular noradrenaline content
      in the frontal cortex, suggesting a specific action of the diet on the
      serotonergic system. Therefore, the administration of a TRP-free amino acid diet
      offers a non-pharmacological means for effectively decreasing brain 5-HT release.
      This diet can be used to study the physiological and behavioral effects of
      reduced brain 5-HT function.

PMID- 10906487
TI  - An improved method for avulsion of lumbar nerve roots as an experimental model of
      nitric oxide-mediated neuronal degeneration.
AB  - A root avulsion lesion on the spinal nerve of adult animals is a useful technique
      to make a model for axotomy-induced motoneuronal degeneration, which is thought
      to be mediated by nitric oxide (NO). Here, we show a simplified version of
      extravertebral avulsion in the young adult rat. The L4 nerve always runs under
      the transverse process of the L5 vertebra, which is located just rostral to the
      delineation of the iliac crest. We used the iliac crest as a clue for the
      identification of the L4 nerve during surgery, including before skin incision. In
      almost all animals the L4 nerve was successfully avulsed at the exit point from
      the spinal cord. This experimental result was similar to that shown in the
      previous literature; the number of either Nissl-stained or ChAT-immunoreactive (
      ir) motoneurons (MN) gradually decreased, while NOS immunoreactivity was induced
      in the MN after avulsion. Furthermore, a combined method of confocal laser
      scanning microscopy and double fluorescent procedures carried out in this model
      suggested the existence of cellular interaction between NOS-ir MN and OX42-ir or
      ED1-ir microglia. It is concluded that this simple and fast method of spinal root
      avulsion is very useful for making a reproducible model of NO-mediated MN cell
      death, with which the mechanism of neuronal cell death, including neuron-glia
      interaction, can be further explored.

PMID- 10906488
TI  - Analysis of the molecular heterogeneity of the microtubule-associated protein tau
      by two-dimensional electrophoresis and RT-PCR.
AB  - The microtubule-associated protein tau is a member of a group of proteins,
      promoting assembly and stabilization of microtubules. In several tauopathic
      neurodegenerative disorders, namely Alzheimer's and Pick's disease and
      frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP 17) this
      protein is converted into fibrilar polymers which form the component of insoluble
      proteanous deposits such as neurofibrillary tangles. The formation of these
      fibrils is believed to interrupt the physiological function of neurons resulting
      in degeneration and cell death. Tau protein exists as a family of heterogeneous
      isoforms derived by both, differential splicing of tau-mRNA and posttranslational
      modification of the protein. Since the role of the different isoforms during the
      process of neurodegeneration is not well understood and as their balance might be
      altered in some cases of tauopathies (Spillantini et al., Proc. Natl. Acad. Sci.
      USA 1998;95:7737-7741), the detailed analysis of the molecular heterogeneity
      gained outstanding interest. The method presented here allows the analysis of
      both, differential splicing and phosphorylation of tau protein by the application
      of two-dimensional (2D) electrophoresis and Western blot detection. Tau protein
      isoforms could be identified from the 2D pattern of dephosphorylated tau in
      concordance with the results of tau-mRNA analysis by RT-PCR. The protocol
      presented was successfully applied to analysis of tau isoforms of human brain
      (Janke et al., FEBS Lett. 1996;379:222-226) and of several species, revealing a
      phylogenetic correlation of tau protein patterns in mammals (Janke et al., Mol.
      Brain Res. 1999;68:119-128). The present paper provides a detailed description of
      the technique and discusses its prospects and limits.

PMID- 10906489
TI  - The novel PCR-based technique of genotyping applied to identification of
      scrambler mutation in mice.
AB  - For a wide range of research purposes it is necessary to perform genotyping, i.e.
      to test which alleles, each corresponding to a particular locus, are present in
      the individual genome. Here we suggest a protocol of genotyping for mice with
      scrambler (scm) mutation. This mutation results in the aberrant splicing of the
      corresponding mRNA and affects the expression of mdab1 protein. Traditional
      approaches using genomic Southern hybridization or PCR with specific primers are
      not suitable for the genotyping of scm because of the lack of comprehensive
      information on the organization of the gene and on the presence of repetitive
      sequences in the known region. Here we propose a quick and highly reproducible
      method for genotyping scm mutant mice. The protocol consists of the following
      steps: isolation of genomic DNA, digestion with the restriction endonuclease,
      anchoring of resulting fragments with the adapter, and PCR amplification using
      adapter-specific primers. The final product of PCR amplification has a
      characteristic length which is different for the wt (wild type) and scm alleles.
      Thus, the characteristic pattern of bands obtained for each individual mouse
      specimen serves as criteria for the presence of wild type and/or scm allele. We
      believe that this approach could have wider application. The protocol can be
      easily modified and used as a convenient tool for identification of other genomic
      defects including those artificially introduced into genome by knockout or gene
      trap techniques.

PMID- 10906490
TI  - Primary cultures of brain microvessel endothelial cells: a valid and flexible
      model to study drug transport through the blood-brain barrier in vitro.
AB  - Studies on drug entry into the brain and permeation of the blood-brain barrier
      start to gain more and more importance in neuropharmaceutical research in order
      to develop new drugs for the therapy of central nervous system diseases.
      Procedures that provide quick access to permeation properties of those drugs with
      high throughput are difficult to achieve with animal models. Although various
      useful cell culture models approaching this issue have been described, results
      are often not comparable among each other unless determined with an equal
      experimental setup. Reproducibility of cell culture methods as well as
      corresponding findings gathered with these tools are often impeded due to the
      lack of details in experimental manuals. Here we present a precise manual for
      preparation and maintenance of porcine brain microvessel endothelial cells,
      serving as a culture model of the blood-brain barrier. Furthermore experimental
      details for blood-brain barrier transport investigations are presented.
      Validation of this model was carried out by determination of bioelectric
      properties and permeation experiments using various marker molecules reflecting
      paracellular and transcellular blood-brain barrier penetration. Results obtained
      with our model are closely resembling the in vivo-situation although astrocytes
      are not included. This simplification of the system is one of the major
      advantages towards robot derived cell cultures necessary for high throughput
      screening.

PMID- 10906492
TI  - Resazurin detection of energy metabolism changes in serum-starved PC12 cells and
      of neuroprotective agent effect.
AB  - Resazurin is a dye, which becomes fluorescent when reduced by oxidoreductases
      within viable cells. Measurement of resazurin fluorescence is therefore an
      indicator of the cell's energy metabolism. Resazurin was used here to detect
      metabolic changes in PC12 cells following serum starvation. Serum withdrawal is a
      cytotoxic environmental change resulting in cell death in cultured cell lines as
      well as in primary cells of various tissue origins, including nerve cells. In
      particular, PC12 cells have been widely employed as a neuronal cell model and a
      large number of studies generated. Many molecular and morphological changes occur
      in PC12 cells after serum withdrawal, and apoptotic cell death is the final
      consequence. We show that resazurin can detect the metabolic impairment in serum
      deprived PC12 cells and can measure the neuroprotective properties of PACAP 1-38,
      as early as day 1 after serum withdrawal. Resazurin constitutes an advantageous
      tool to discriminate between healthy and metabolically impaired cells, since
      fluorescence produced by the reduced dye can be measured in living cells without
      a lysis step. The experiment is fast, inexpensive, uses a small amount of cells
      and can easily be automated.

PMID- 10906491
TI  - Electrophoretic mobility shift assay for the detection of specific DNA-protein
      complex in nuclear extracts from the cultured cells and frozen autopsy human
      brain tissue.
AB  - The electrophoretic mobility shift assay (EMSA) is generally used to study the
      interaction of transcription factors to specific DNA sequences. The preparation
      of high quality nuclear extracts is an important step before performing the
      assay. Here we describe a rapid method for the isolation of good-quality DNA
      binding proteins from cultured cell lines and autopsy tissue samples from the
      human brain. The 'rapid method' (RM) utilizes the low salt/detergent lysis steps
      followed by high salt extraction of nuclei. To test and compare the activity of
      nuclear extracts prepared by the standard and 'rapid' methods for its ability to
      form the specific DNA-protein complex, EMSA was carried out with three different
      oligonucleotide probes: AP1, NF-kappaB and URE. A comparative study indicates
      that the capacity to form the specific DNA-protein complex with these
      oligonucleotide probes by standard and RM nuclear extracts was very similar. Each
      nuclear extract formed the corresponding DNA-protein complex, the specificity of
      which was checked by the competition experiment. In some cases unspecific bands
      were observed and which were present in nuclear extracts from both preparations.
      Thus the simplicity of the 'rapid method' permits the preparation of nuclear
      extracts from several cell lines and tissue samples at the same time at much
      shorter time than the 'standard' method without compromising the DNA-binding
      activity. The RM can be applied to determine the cell type or tissue specificity
      of transcription factors in an efficient, economical and consistent manner.

PMID- 10906493
TI  - Immunofluorescence and biochemical techniques to detect nuclear localization of
      ciliary neurotrophic factor in glial cells.
AB  - Ciliary neurotrophic factor (CNTF) promotes the survival of several populations
      of neurons, including sensory and motor neurons. It is mainly produced by Schwann
      cells and astrocytes and exerts its biological function via a specific membrane
      receptor. We recently determined the nuclear localization of CNTF in producing
      cells, after transfection and in the heterologous system of Xenopus oocytes. In
      the present paper, we describe in detail the techniques for the detection of CNTF
      in the nucleus of rat astrocytes, transfected cells, isolated nuclei and injected
      Xenopus oocytes.

PMID- 10906494
TI  - Culturing neuronal cells on surfaces coated by a novel polyethyleneimine-based
      polymer.
AB  - Maintaining cells in culture is essential for studying many aspects of cell
      biology and physiology. Cell culturing is dependent on proper anchorage of cells
      to the growth surfaces. For most cell lines, and especially for post-mitotic
      neurons, coated tissue culture plates are prerequisite for seeding. The most
      commonly used coating reagents are positively charged polymers such as poly-L
      lysine or biologically purified adhesive molecules such as collagen. In this
      report, we present a simple procedure for synthesizing and for coating cell
      culture surfaces. The reagent is a biologically inert hydrophobized
      polyethyleneimine (PEI), which provides adequate adhesive properties for cultured
      cell lines including those of neuronal lineage. The hydrophobized PEI is branched
      PEI modified by octadecanyl groups bound to 2 mol% of the amino groups of the
      PEI. Unlike the native PEI that is water soluble, the modified PEI is soluble in
      ethanol, and thus resistant to solubilization in biological media. The protocol
      of coating was optimized for tissue culture plates as well as glass surfaces and
      in many respects this polymer outperformed other routinely used coating reagents.
      Neuronal cell lines, plated on the polymer-treated surfaces are resistant to
      manipulations including repeated media changes and extensive washing. The
      advantage of coating surfaces with the developed PEI-based polymer compared to
      other commonly used coating reagents is discussed.

PMID- 10906495
TI  - Molecular localisation of a G-protein mRNA using differential display and in situ
      hybridization.
AB  - Defining molecular repertoires within virally infected tissues of the nervous
      system may provide insight into the pathogenesis of, and immunity to, neurotropic
      viruses. Here we report the application of such a method, namely mRNA
      differential display (DD), to the identification of mRNAs that are expressed at
      different levels in herpes simplex virus (HSV) infected nervous tissue from
      immunocompetent and CD8(+) lymphocyte depleted mice. Small amounts of input RNA
      can be used by DD, making the method ideal for experiments based on murine
      sensory ganglia (DRG), which on average yield less than 0.5 microg of total RNA.
      In the current work, DD facilitated the identification of a mRNA whose abundance
      in HSV-infected ganglia, based on Northern blot analysis, was reduced in mice
      depleted of CD8(+) cells. The cloned product of this mRNA was of particular
      interest to our research as sequence data strongly suggested that it represented
      the murine homologue of the alpha chain of a G protein termed Golf. This G
      protein had not previously been reported from dorsal root ganglial tissue. RT-PCR
      confirmed the presence of Golf in DRG and in situ hybridization studies localised
      this molecule to primary sensory neurons. These data indicate that DD is
      sufficiently robust to be applied to the study of virus pathogenesis within the
      nervous system.

PMID- 10906496
TI  - Double immunocytochemistry for the detection of Fos protein in retrogradely
      identified neurons using cholera toxin B subunit.
AB  - The focus of this paper was to describe a method combining the neuroanatomical
      technique of retrograde transport of cholera toxin B subunit (CTB) with the
      technique of Fos functional labeling. This method allowed us to evaluate whether
      neurons identified by retrograde tracing were activated following chemical
      stimulation of another brain area. We have used this method at the light
      microscopic level to determine whether the stimulation of the rostral
      ventrolateral medulla activated retrogradely labeled adrenal sympathetic
      preganglionic neurons in the spinal cord. CTB-containing neurons, Fos
      immunoreactive neurons and double labeled neurons were observed in spinal
      autonomic areas. These results suggest that the rostral ventrolateral medulla
      exerts a descending activation upon identified adrenal preganglionic neurons. The
      method described in this protocol can be applied for other brain areas in order
      to establish if a given structure can activate an identified population of
      neurons linked with a particular target of central or peripheral nervous system.

PMID- 10906497
TI  - Combined TUNEL and double immunofluorescent labeling for detection of apoptotic
      mononuclear phagocytes in autoimmune demyelinating disease.
AB  - Apoptosis is usually associated with genomic DNA fragmentation which can be
      detected in situ by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP
      nick-end labeling (TUNEL) assay. We describe a combined TUNEL and double
      immunofluorescent labeling technique to determine the fate of inflammatory
      infiltrates and resident glial cells in the central nervous system following the
      onset of an autoimmune demyelinating disease such as experimental allergic
      encephalomyelitis (EAE) in rats. Anti-digoxigenin (anti-DIG) antibody conjugated
      with 7-amino-4-methylcoumarin-3-acetic acid (AMCA) emitting blue fluorescence was
      used to detect apoptotic cell DNA, which was already labeled by modified TUNEL
      using alkali-stable DIG-11-dUTP. Anti-mouse IgG secondary antibody conjugated
      with Texas Red emitting red fluorescence was used to detect anti-rat CD11b
      primary antibody (clone OX-42) directed to the surface antigen of mononuclear
      phagocytes including microglia. Using this technique, we detected apoptotic
      mononuclear phagocytes (co-labeled with blue and red fluorescences) in the spinal
      cord sections of rats with EAE.

PMID- 10906498
TI  - Hydra biological detection of biologically active peptides in rat cerebrospinal
      fluid.
AB  - The Hydra bioassay system utilizes a tentacle ball formation (TBF), a component
      of the feeding response of hydra, elicited by S-methyl-glutathione. TBF is
      modulated by many biologically active peptides in a specific way to individual
      peptides, and is useful in investigating biologically active peptides in a
      complex biological sample. We applied the hydra bioassay to explore a possible
      biologically active substance responsible for the decrease in the motor activity
      of the mice. The suppression of the CSF obtained from rats after exhaustive
      exercise was marked lower than that of sedentary rats. Addition of transforming
      growth factor-beta (TGF-beta), which is the only substance known to nullify TBF,
      to CSF of the sedentary rat reproduced this change in the suppression of the TBF.
      This system is useful to screen active peptides in small amounts of biological
      samples containing very low concentrations of peptides.

PMID- 10906500
TI  - Efficacy and side effects of immediate postcoital levonorgestrel used repeatedly
      for contraception. United Nations Development Programme/ United Nations
      Population Fund/World Health Organization/World Bank Special Programme of
      Research, Development and Research Training in Human Reproduction, Task Force on
      Post-Ovulatory Methods of Fertility Regulation. vonhertzenh@who.ch.
AB  - We evaluated the efficacy and side effects of immediate postcoital administration
      of levonorgestrel 0.75 mg used repeatedly for contraception. A total of 295
      healthy women with infrequent coitus were enrolled at 6 study sites. Each woman
      took levonorgestrel 0.75 mg by mouth immediately after intercourse during 6
      months as her only method of contraception. We collected data on side effects and
      acceptability and calculated the Pearl index failure rates over 133 woman-years
      of use by standard methods. The Pearl index failure rate was 6.8 (95% CI 3.1
      12.9) pregnancies per 100 woman-years of use. The overall probability of
      pregnancy per treated coital act was 1.4 per 1000. Approximately one-third of
      participants discontinued the study within 6 months (mainly for bleeding
      problems). Menstrual complaints were reported by 70% of women. Other complaints
      included (in decreasing order) nausea, breast tenderness, weakness, dizziness,
      headache, abdominal bloating, loss of libido, depression, and vomiting. High-dose
      levonorgestrel pills are unsuitable for regular postcoital contraception.

PMID- 10906499
TI  - Efficacy, cycle control, and safety of two triphasic oral contraceptives:
      Cyclessa (desogestrel/ethinyl estradiol) and ortho-Novum 7/7/7
      (norethindrone/ethinyl estradiol): a randomized clinical trial.
AB  - The contraceptive efficacy, cycle control, and safety of a new low-dose,
      triphasic desogestrel/ethinyl estradiol oral contraceptive (CTR 77, Cyclessa(TM))
      was compared to that of a marketed, triphasic norethindrone/ethinyl estradiol
      oral contraceptive (Ortho-Novum(R) 7/7/7). Two identical multicenter, open-label,
      randomized, parallel group, comparative Phase III 6-cycle trials were designed to
      each enroll 4200 healthy women. The combined comparative data for Cyclessa versus
      Ortho-Novum 7/7/7 for both studies are reported here. Cyclessa and Ortho-Novum
      7/7/7 had comparable contraceptive efficacy. Despite a lower ethinyl estradiol
      dose (25 microg/day vs. 35 microg/day), the Cyclessa group had significantly
      improved cycle control in comparison to the Ortho-Novum 7/7/7 group for presence
      of a withdrawal bleed (p = 0.001), lack of early withdrawal bleed (p = 0.01), and
      breakthrough bleeding/spotting (p = 0.001). For each of the months of the study,
      the incidence of breakthrough bleeding/spotting was lower in the Cyclessa group
      than the Ortho-Novum 7/7/7 group (breakthrough bleeding, p = 0.006; breakthrough
      spotting, p = 0.001). The incidence of other adverse events was similar among
      treatment groups, an observation that supports the safety of both formulations.
      There was significantly less weight gain (p = 0.0002) and less increase in the
      body mass index (BMI) (p = 0.0002) in the Cyclessa group. The contraceptive
      efficacy and safety of Cyclessa is comparable to Ortho-Novum 7/7/7. Cyclessa
      provides significantly improved cycle control with no weight gain.

PMID- 10906501
TI  - Mesigyna once-a-month combined injectable contraceptive: experience in Latin
      America.
AB  - A phase III clinical study was carried out among 534 fertile Latin American women
      to evaluate cycle control, side effects, and contraceptive efficacy of a once-a
      month combined injectable, Mesigyna, consisting of 50 mg norethisterone enanthate
      and 5 mg estradiol valerate. The pregnancy rate at 1 year was 0 per 100 woman
      years for a total experience of 4688 woman-months. The overall discontinuation
      rate at one year was 17.9%. Discontinuation rate for bleeding problems was 5.1%.
      The Colombian women had a significant increase (p <0.001) in bleeding problems
      compared to other countries. The discontinuation rate for amenorrhea was 1.1%.
      There were no significant differences between the groups regarding
      discontinuation for other medical or non-medical reasons. Mean weight gain after
      one year of use was 1.02 kg. Mesigyna is an appropiate once-a-month injectable
      contraceptive for Latin American women since it is highly effective and its
      perception of normal menstrual bleeding is of importance in the Latin American
      population.

PMID- 10906502
TI  - Premenopause contraception with monthly injectable Mesigyna with special emphasis
      on serum lipid and bone density patterns.
AB  - This 2-year study compared Mesigyna(R) administered to 49 pre-menopausal women
      between 38 and 50 years, to 99 women fitted with an IUD (Nova-T). A complete
      lipoprotein assessment was carried out before treatment and at 6, 12, and 24
      months of treatment. A bone densitometry was performed on half of the women, and
      an endometrial biopsy was taken from half of the Meisgyna group before and at the
      end of the first and second year. No pregnancy occurred with Mesigyna use while
      three pregnancies were observed with the IUD. The incidence of bleeding anomalies
      was higher in the Mesigyna group, with a discontinuation rate for these reasons
      of 20% versus 4% for IUD (p <0.05). The duration of bleeding days as well as
      dysmenorrhea were less with Mesigyna. No differences were seen in the pattern of
      intermenstrual bleeding and spinal bone density between both groups. No patient
      developed endometrial hyperplasia after treatment, thus endometrial risk seemed
      not to be increased. Total and LDL cholesterol, and apolipoproteins did not show
      modifications. A slight decrease in total triglycerides, HDL and HDL(2)
      cholesterol, and IDL lipoproteins was observed with Mesigyna. The present study
      appears to be the first using a monthly injectable hormonal contraceptive and
      monitoring its influence on lipid patterns in premenopausal women. Mesigyna
      proved to be a highly effective and low risk agent for premenopausal users.

PMID- 10906503
TI  - Tubal ligation and risk of cervical cancer. The World Health Organiztion
      Collaborative Study of Neoplasia and Steroid Contraceptives.
AB  - Data from a hospital-based case-control study collected in eight countries were
      analyzed to determine whether tubal ligation alters risk of invasive squamous
      cell cervical cancer. Study subjects included 2339 cases aged 22 to 64 years with
      newly diagnosed squamous cell cervical cancer in 10 participating medical
      centers, and 13,506 hospitalized controls matched on age and place of residence
      to the cases. After adjustment for age, center, caesarian section, number of live
      births, number of marriages or other sexual relationships, age at first sexual
      relationship, and frequency of Pap smears, a small decrease in risk was observed
      during the first 5 postoperative years. Tubal ligation probably provides an
      opportunity for secondary prevention of cervical cancer.

PMID- 10906504
TI  - Progesterone release from glutaraldehyde cross-linked casein microspheres: in
      vitro studies and in vivo response in rabbits.
AB  - Microspheres of bovine milk protein casein loaded with progesterone were
      fabricated by glutaraldehyde cross-linking of an aqueous alkaline solution of the
      protein dispersed in a hexane and dichloromethane non-aqueous dispersion medium
      with an aliphatic polyurethane as the stabilizer. Microspheres were characterized
      for their surface morphology and internal structure using scanning electron
      microscopy. In vitro release studies in phosphate buffer at 37 degrees C
      demonstrated that the rate of release of the steroid from the microsphere matrix
      was a function of cross-linking density, particle size, and drug payload.
      Microsphere formulations released 50% to 60% of the incorporated steroid in about
      30 days and, thereafter, attained a steady state. In the presence of a protein
      digesting enzyme such as protease, complete release of the steroid was observed
      in about 4 days in vitro into phosphate buffer. Intramuscular injection of
      progesterone-loaded microspheres into rabbits showed a plasma concentration of 1
      to 2 ng/mL up to 5 months without any significant burst effect, whereas the
      powdered steroid administered in saline demonstrated a large burst effect peaking
      over 20 ng/mL, and the plasma concentration was not sustained beyond 4 days. Data
      obtained suggest that casein microspheres would be promising as a biodegradable
      drug carrier for sustained delivery of steroids.

PMID- 10906505
TI  - Effects of composite root extract on histological structures of graffian follicle
      and endometrial epithelium in albino rat.
AB  - This study attempted in vivo testing of a group of plant root extracts in
      composite form on the reproductive organs of the female albino rat. These roots
      in composite form have been used by the folk women of Assam to prevent pregnancy.
      Firsthand knowledge revealed that the dry powder of these roots in composite form
      can induce sterility in women temporarily (reversible) or permanently which is
      dose-dependent when taken through oral route. The study revealed that
      administration of ethanolic crude extract of these composite roots in a dose of
      1000 mg/kg/day, consecutively for 12 days, can modulate histological changes in
      the structures of ovary and uterus. This dose has previously been detected as the
      threshold dose to induce sterility (reversible) in albino rat. The ovarian
      follicle showed structural disparity in thecal cells and granulosa cells, and
      formation of zona pellucida. In the uterus, the endometrial epithelium on the
      luminal surface showed pseudostratification, vacuolation of the cells, and
      irregular desquamation from the stroma. Infiltration of a large number of
      polymorphs in the endometrial stroma and necrosis of endometrial gland tissues
      indicated structural and functional aberrations of the uterus.

PMID- 10906506
TI  - Anordiol produces pregnancy loss in the rat--via the embryo or via the uterus?
AB  - Anordiol, the dihydroxylated metabolite of anordrin, is an antiestrogen with
      estrogenic activity that is known to inhibit fertility. The following study was
      conducted to determine the mechanism of this antifertility effect. Anordiol was
      administered orally to rats, prior to implantation, on Day 2 of pregnancy.
      Control animals were treated with the vehicle only. The effectiveness of the
      agent in terminating pregnancy was determined on Day 14 of pregnancy. Anordiol
      was 100% effective in abolishing pregnancy at a dose of 0.6 mg/Kg. Administration
      of smaller doses resulted in a decreased number of implanting embryos, in a dose
      dependent manner. An additional dose of anordiol on Day 3 of pregnancy yielded
      similar results. To determine whether pregnancy impairment by anordiol is exerted
      via the embryo or via the uterus, reciprocal embryo transfers were performed. Day
      5 blastocysts were transferred into the uteri of pseudopregnant rats. In one set
      of experiments, the donor rats were treated with anordiol, and in the second set
      the recipient rats were treated. The results indicate that the effects of
      anordiol administration are exerted via the embryo as well as the uterus.

PMID- 10906507
TI  - Uterine perforation with Lippes loop intrauterine device-associated
      actinomycosis: a case report and review of the literature.
AB  - A case of a 67-year-old postmenopausal woman, gravida 2, para 2, with an uterine
      perforation from actinomycotic infection with Lippes loop IUD is reported. She
      had the Lippes loop IUD inserted for 35 years, and had never had any pelvic
      examination nor Papanicolaou smear. She presented with acute abdominal pain. The
      clinical picture mimicked peptic ulcer perforation. The woman underwent
      laparotomy and exudative fluid was discovered in the abdominal cavity with the
      tip of the Lippes loop IUD at one of the two small holes of the uterine fundus.
      Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed.
      The postoperative microscopic pathological report demonstrated characteristics of
      actinomycosis. She was treated with parenteral high-dose penicillin for 4 weeks
      followed by oral penicillin for 6 months. The woman had an uneventful recovery.
      To our knowledge, this is the first case report of uterine perforation due to
      Lippes loop IUD-associated actinomycotic infection.

PMID- 10906508
TI  - Increased depolarization, prolonged recovery and reduced adaptation of the
      resting membrane potential in aged rat skeletal muscles following eccentric
      contractions.
AB  - Previously it was shown in young-adult muscles that eccentric contractions (EC)
      produce a significant (24 h) depolarization of the resting membrane potential
      (RMP), and that in-vitro (Gd(3+)) and in-vivo (streptomycin) blockade of stretch
      activated ion channels (SAC) result in a partial repolarization of the RMP. The
      portion of the depolarization not restored by SAC blockade is believed to be from
      sarcolemmal injury. A second exposure to EC results in less depolarization and a
      more rapid recovery of the RMP. Aged muscles were subjected to the same EC
      protocol to test the hypotheses that: (1) Aged muscles will experience a more
      significant and prolonged depolarization of the RMP following EC. (2) The
      depolarization in aged muscles will occur by a greater contribution from membrane
      damage, rather than the opening of SAC. (3) The aged muscles will demonstrate a
      reduced capacity to adapt to EC, and will experience a similar degree of
      depolarization following repeated exposures to EC. The results indicate a
      significantly greater and longer lasting depolarization in aged compared to young
      adult muscles. Blocking SAC did not produce a repolarization of the RMP in aged
      muscles. Aged muscles had a significantly reduced adaptive response to EC
      compared to young-adult. It is speculated that the different response in aged
      muscles results from a reduced number of functional SAC.

PMID- 10906509
TI  - Effects of aging on expression of genes involved in regulation of proliferation
      and apoptosis in the colonic epithelium.
AB  - The purpose of this study was to characterize the effects of aging on colonic
      messenger ribonucleic acid (mRNA) and protein levels of genes involved in the
      regulation of cell proliferation and apoptosis, and epithelial morphology in male
      Fischer 344 rats. Our study shows that, with aging, colonic expression of insulin
      like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) is significantly
      increased and decreased, respectively. Colonic Bax protein levels are increased
      significantly with aging. Immunohistochemical localization of Bax protein shows a
      greatly increased expression in colonic crypts, especially in the upper portion
      of crypts. p53 expression is unchanged with aging. No significant change in
      proliferation of colonic crypt cells is observed by bromodeoxyuridine (BrdU)
      labeling, although the increased colonic expression of IGF-1 and the decreased
      expression of IGFBP-3 with aging may result in an increased colonic IGF-1
      bioactivity. The age-related changes in Bax and IGFBP-3 appear to be independent
      of p53. The finding of an unchanged colonic epithelium with aging in the face of
      a greatly increased Bax protein levels may suggest that the elevated Bax protein
      levels function to render colonic epithelial cells more sensitive to apoptotic
      stimuli.

PMID- 10906510
TI  - cDNA expression arrays reveal incomplete reversal of age-related changes in gene
      expression by calorie restriction.
AB  - Calorie restriction (CR) extends life span and retards many age-related cellular
      and molecular changes in laboratory rodents. However, neither the breadth of its
      effects, its underlying mechanisms, nor the limits of its action is fully
      understood. Expression levels of 588 genes in livers from 3- and 24-month-old ad
      libitum-fed (AL), and 24-month-old CR (60% of AL intake) male C57BL/6J mice (four
      per group) were measured. Six genes met the statistical criteria for differential
      expression in old AL compared to young AL mice. Only one of these age-related
      changes was attenuated by CR. Four additional gene products, that did not change
      with age in AL mice, were differentially expressed in old CR compared to old AL
      mice. Northern and RT-PCR analyses confirmed differential expression of four of
      the six candidate genes identified by the array results. Many of the identified
      genes have not previously been reported to be affected by CR or aging. Some of
      the age-related changes in gene expression are consistent with an increased
      vulnerability of the aged liver to carcinogenic or other insults, with only
      partial protection against insult by CR. Incomplete reversal by CR of age-related
      changes in gene expression provides a potentially important path for probing the
      limits of CR action. These results also show the importance of independent
      confirmation in expression array profiling of age-related changes in gene
      expression.

PMID- 10906511
TI  - Changes in biological characteristics during the cellular aging of ligament
      fibroblasts derived from patients with prolapsus uteri.
AB  - Prolapsus uteri in pelvic support disorders are common in elderly women. The
      etiology is unclear and more likely to be multifactorial. We examined changes in
      biological characteristics and responsiveness to growth factors during the in
      vitro cellular aging of cardinal ligamental fibroblasts derived from patients
      with prolapsus uteri (HPLiF), and compared them with those of cells from age
      matched control subjects (HCLiF). HPLiF and HCLiF had almost the same in vitro
      life span and the age-related patterns of biological parameters were essentially
      the same. However, the saturation density was significantly higher in HPLiF than
      in HCLiF. Furthermore, the high proliferative activity of HPLiF to serum
      mitogens, especially to platelet-derived growth factor, was retained throughout
      the in vitro life span. p53 protein levels in HPLiF increased at late passages,
      but were significantly less than in aged HCLiF. These results indicate that the
      higher proliferative activity in prolapsus fibroblasts may result from the
      decreased expression of p53 protein and may lead to a decrease in the synthesis
      and deposition of extracellular matrix components. These results support the
      hypothesis that functional alterations in ligament fibroblasts are involved in
      the mechanism of the development of prolapsus uteri.

PMID- 10906512
TI  - Overexpression of mRNAs of TGFbeta-1 and related genes in fibroblasts of Werner
      syndrome patients.
AB  - We analyzed mRNAs that were up- or down-regulated in fibroblasts from Werner
      syndrome (WS) patients compared with those from normal individuals. The mRNAs
      from normal and WS cells were first screened by differential display, and those
      mRNAs that were apparently up- or down-regulated were selected except for mRNAs
      related to extra-cellular matrix (ECM) proteins that are already known to be up
      regulated in WS fibroblasts. Then, the expression levels of these mRNAs were
      semiquantified by northern blot analysis, and six up-regulated and two down
      regulated mRNAs were identified in WS cell lines. Among the six up-regulated
      mRNAs were three mRNAs that coded TGFbeta-1 and two proteins, their expressions
      of which were increased by TGFbeta-1. These results together with the fact that
      TGFbeta-1 up-regulates the expression of ECM proteins strongly suggest that
      TGFbeta-1 has a key role in accelerated cellular senescence of fibroblasts of WS
      patients.

PMID- 10906513
TI  - Program for testing biological interventions to promote healthy aging.
AB  - The National Institute on Aging (NIA) sponsored a workshop on September, 1999 to
      discuss the feasibility of establishing a program to evaluate potential
      intervention strategies to decelerate the rate of aging in mammals. The ultimate
      goal is to identify promising interventions in animals that might lead to
      clinical trials in humans. The participants discussed various animal models,
      biological endpoints and possible structure of such a program. The ability to
      implement such a program will require a decision by NIA staff about whether the
      anticipated benefits to be derived from identification of effective interventions
      under well controlled conditions in an animal model, in this case the mouse,
      would justify the anticipated cost of the testing program.

PMID- 10906514
TI  - Mucosal swabs detect HPV in laryngeal papillomatosis patients but not family
      members.
AB  - Seven patients, aged 2-7 years, with active recurrent respiratory papillomatosis
      (RRP) attending the University of Michigan Pediatric Otolaryngology Clinic were
      studied to determine if human papillomavirus (HPV) is harbored in sites of the
      upper aerodigestive tract other than in the laryngeal papilloma itself. We also
      determined if close family members had detectable virus in their oral cavities.
      Noninvasive swabs of buccal mucosa, posterior pharynx, nasal vestibule, and
      tonsillar pillar of patients, as well as buccal mucosa and posterior pharyngeal
      swabs of family members were studied. Swabs of the patients' papillomas served as
      the positive controls. HPV was detected using polymerase chain reaction (PCR)
      amplification and Southern hybridization techniques. Six of seven patients had
      detectable HPV in papilloma and endolaryngeal swabs. Four were HPV type 6, and
      two were HPV type 11. The patient whose swab was negative for HPV was found to be
      biopsy negative for papilloma 3 weeks after a single laser excision which was
      performed 6 months prior to the endolaryngeal swab. HPV types 16, 18 and 31 were
      not found in any of the patients. No swabs from other sites in patients or family
      members were HPV positive despite the presence of adequate DNA in the swabbed
      material for successful amplification of beta-actin sequences. The absence of HPV
      (other than in the papilloma itself) in the upper aerodigestive tract of patients
      and caregivers is consistent with the absence of reported cases of horizontal
      transmission to siblings or other family members. The findings are also
      consistent with the conventional view that juvenile respiratory HPV is
      transmitted vertically from vaginal condylomas in the mother.

PMID- 10906515
TI  - Consequences of adenoidectomy in conjunction with tonsillectomy in children.
AB  - OBJECTIVE: The purpose of this prospective study was to investigate the role of
      adenoidectomy in children undergoing elective adenotonsillectomy. PATIENTS AND
      METHODS: All consecutive children less than 15 years of age operated on over a 12
      month period were included. Adenoidectomy was done with curettes and forceps
      under mirror visualization and tonsillectomy with a unipolar electrodissection
      technique. Duration of the operation, intra-operative blood loss, and post
      operative complications were recorded. RESULTS: Adenotonsillectomy was done in 98
      children with a mean age of 7.8 years. The mean duration of adenoidectomy was
      10.3 min (S.E. 0.7), 51.8% of the time used for adenotonsillectomy and 25. 9% of
      the total operating room time. The blood loss was 43.6 ml (S.E. 5.4) and 7.8 ml
      (S.E. 2.5) for adenoidectomy and tonsillectomy, respectively. Both the duration
      (P=0.04) and blood loss (P=0.0005) of adenoidectomy increased significantly with
      the increasing age of children. Post-adenoidectomy complications did not occur.
      CONCLUSION: Even though adenoidectomy prolonged the operating time and increased
      the intra-operative blood loss, especially in older children the procedure in
      general remained relatively short and safe. However, adding adenoidectomy to
      tonsillectomy should always be carefully considered, particularly in children 10
      years or older operated on principally because of palatine tonsil disease.

PMID- 10906517
TI  - Treatment of otitis media with effusion in children with mucopolysaccharidoses.
AB  - Otitis media with effusion (OME) is a constant finding in children with
      mucopolysaccharidoses (MPS). Affected children may also present the anaesthetist
      with a difficult airway. A 7-year retrospective review of the management of OME
      in individuals with MPS was carried out. Nine patients were identified. All had a
      number of short-term ventilation tube insertions (one to four, mean two) before a
      diagnosis of MPS was made. Following diagnosis three required repeated short-term
      ventilation tubes insertions (two to four, mean three), four had long-term
      ventilation tube insertions once only. Five children who had residual hearing
      loss were provided with hearing aids but compliance was poor in two. Once a
      diagnosis of MPS has been made, a hearing aid, if compliant, or a long-term
      ventilation tube would be a better option than a short term one in order to
      minimise the anaesthetic risk. A 'watch and wait' policy is not recommended.

PMID- 10906516
TI  - Office-based laser assisted tympanic membrane fenestration in adults and
      children: pilot data to support an alternative to traditional approaches to
      otitis media.
AB  - OBJECTIVES: To determine the role of intermediate duration ( approximately 3
      weeks) middle ear ventilation using office-based laser assisted tympanic membrane
      fenestration in resolving an episode of otitis media with effusion in adults and
      children who otherwise would have been treated with insertion of pressure
      equalization tubes. METHODS: A retrospective chart review of 92 patients (162
      ears) was conducted to identify the utility and technical challenges associated
      with laser assisted tympanic membrane fenestration in an office setting. Clinical
      characteristics reviewed included: age, gender, duration of effusion, season
      performed, and hearing and health status of middle ear upon healing of the
      fenestration. RESULTS: 69% of all patients were effusion free upon closure of the
      fenestration; 68% of those <3 years; 70% of those 3-7 years; and 70% of those 25
      80 years. Some episodes recurred and at final follow-up 64% had normal middle ear
      structure and function (range of follow-up =1-18 months, mean 2.5 months, median
      2.0). Shorter duration of effusion pre-fenestration was more often associated
      with return to normal middle ear structure and function (P<0.01). Season
      performed, number of previous episodes of otitis media and pre-treatment
      tympanometry were not predictive of result. No significant complications were
      observed. CONCLUSIONS: The use of office-based laser assisted tympanic membrane
      fenestration is a reasonably safe and effective procedure for the treatment of
      otitis media in most adults and children. As a minimally invasive otologic
      procedure, laser assisted tympanic membrane fenestration has great potential to
      decrease the rates of both antibiotic usage and insertion of ear tubes.

PMID- 10906518
TI  - The effects of mitomycin-C and stenting on airway wound healing after
      laryngotracheal reconstruction in a pig model.
AB  - OBJECTIVE: To assess the effects of mitomycin-C (MTC) and endoscopic stenting on
      airway wound healing after laryngotracheal reconstruction. DESIGN: A prospective,
      blinded, randomized controlled animal study. SUBJECTS: Twenty-six domestic pigs
      (Sus scrofula) divided into four groups. INTERVENTIONS: Each animal underwent
      single-stage laryngotracheal reconstruction (SSLTR) with auricular cartilage
      grafts and stenting. Group 1 animals were sacrificed on postoperative day 3, and
      group 2 animals on postoperative day 7. On postoperative day 7, groups 3 and 4
      underwent endoscopy, stent removal, and application of MTC (0.5 mg/ml) or placebo
      (normal saline). Group 3 animals were sacrificed on postoperative day 14, group 4
      animals on day 21. Two additional animals from each experimental group were
      prepared for election microscopy studies. Segments of reconstructed airway were
      evaluated grossly and histologically for all animals. Additional tonometric
      evaluation was performed on two stents to determine their compressive strength.
      MAIN OUTCOME MEASURES: Healing, reepithelization, graft incorporation, and airway
      diameter. RESULTS: Two-thirds of the animals demonstrated some degree of stent
      collapse on endoscopy. Granulation tissue formation was seen in all animals, and
      resolved with stent removal. No animal experienced airway compromise due to
      granulation tissue formation. Stenting was seen to induce a submucosal
      fibroproliferative response and scarring, with loss of normal glandular
      architecture, in all animals. MTC did not affect the acute inflammatory response,
      reepithelization of the graft site, or formation of the subepithelial
      fibroproliferative response. MTC treated animals, however, demonstrated better
      graft incorporation with fibrocartilage proliferation of the graft. Untreated
      animals demonstrated liquefactive necrosis of the graft, without evidence of
      neochondrification of the graft. CONCLUSIONS: The pig airway is an adequate model
      of wound healing following SSLTR and stenting. Metallic ballon expandable stents
      can be successfully used following SSLTR, allowing for immediate postoperative
      extubation. However, the formation of a submucosal fibroproliferative response
      and mucosal scarring seen in our study raises some concerns with the current
      stent design. Before stenting is widely clinically applied, the optimum stent
      design needs to be developed. Finally, MTC seems to prevent the liquefactive
      necrosis of SSLTR grafts and promote neochondrification, allowing improved graft
      incorporation. Further studies are needed to asses the long-term effects of MTC
      on healing and restenosis, and its effects on cartilage growth and formation,
      following SSLTR.

PMID- 10906519
TI  - Prenatal diagnosis of airway compromise: EXIT (ex utero intra-partum treatment)
      and foetal airway surgery.
AB  - Four cases of potential airway obstruction diagnosed in the early antenatal
      period are presented. Their management is outlined, and the need for a
      multidisciplinary team approach to these problems is highlighted. The experience
      of the ex-utero intrapartum treatment (EXIT) procedure is presented, and the
      first attempt at intra-uterine tracheal surgery is introduced.

PMID- 10906520
TI  - Bronchoscopy for foreign body removal in children. A review and analysis of 210
      cases.
AB  - OBJECTIVE: A foreign body aspiration in the tracheobronchial tree is a dangerous
      and common medical emergency in childhood, with serious and potentially lethal
      consequences. It must be suspected in children with a suggestive history, even
      though the clinical symptoms or radiographic findings are not pathognomonic for
      foreign body aspiration. METHODS: In this study 210 pediatric cases, with a
      suggestive history of foreign body aspiration undergoing bronchoscopy in the last
      8 years in the department, were reviewed. In all cases bronchoscopy was performed
      under general anesthesia using a Storz ventilation bronchoscope with distal cold
      light illumination. RESULTS: In 130 patients a foreign body was discovered, in 17
      cases pus was aspirated and in 63 cases there were no findings. Seventy-eight
      (60%) foreign bodies were found in the right main bronchus, 43 (33.1%) in left
      main bronchus, seven (5.4%) in both bronchi and two (1.5%) were found in the
      subglottic area. The incidence of bronchoscopy during the last 8 years was 28
      procedures per 100000 children population per year in the island of Crete.
      CONCLUSION: More attention should be given to the need for a careful history and
      the use of radiographs as supplemental information to make the decision to
      perform a bronchoscopy. The parents, also, should pay attention not to allow
      children dry fruits and small toys, as well as, teaching their children to avoid
      any physical or emotional activity while having a full mouth.

PMID- 10906521
TI  - Branchio-oculo-facial syndrome.
AB  - Branchio-oculo-facial (BOF) syndrome is a rare autosomal dominant disorder that
      has a distinct phenotype with characteristic craniofacial abnormalities. These
      consist of branchial anomalies, including supra-auricular sinuses, and aplastic
      cervical skin lesions, with possible ectopic dermal thymus, malformed auricles,
      stenotic external auditory canals, conductive hearing loss, ocular abnormalities
      (microphthalmia and lacrimal duct obstruction), and pseudocleft of the upper lip.
      Extracraniofacial malformations are uncommon. We describe two new cases of BOF
      and discuss the classical clinical presentation and differential diagnosis. Our
      two patients presented with facial nerve paralysis and were also were found to
      have inner ear dysplasias with associated sensorineural hearing loss which, to
      our knowledge, have not been described in the literature in association with this
      syndrome.

PMID- 10906522
TI  - Sialoblastoma of the submandibular gland: report of a case and review of the
      literature.
AB  - Sialoblastomas are rare perinatal epithelial salivary tumors, with only 22
      reported cases in the literature. While they have been reported to occur
      predominantly in the parotid gland, we present one case of sialoblastoma of
      submandibular gland origin. The surgical management of this patient is discussed.
      Histopathologic examination, including immunochemical, ultrastructural and
      cytogenetic studies, was performed. Pertinent literature is reviewed.

PMID- 10906524
TI  - Views from the mountaintop: looking back, projecting forward

PMID- 10906523
TI  - Melanotic neuroectodermal tumor of infancy (MNTI) of the hard palate:
      presentation and management.
AB  - OBJECTIVE: To discuss the presentation and management of melanotic
      neuroectodermal tumor of infancy (MNTI) of the hard palate. METHOD: Case
      presentation and literature review. CASE: A 6-month-old girl presented with a
      slow growing, non-tender anterior oral hard palate mass. Radiologic imaging
      revealed a well-circumscribed cystic lesion containing teeth. After excision,
      histopathologic and electron microscopic evaluation revealed MNTI. No recurrence
      was seen at 12-month follow-up. CONCLUSIONS: This case and a review of the
      literature reveal MNTI to be a rare, benign hard palate tumor, which may present
      as a smooth, firm, painless, slow-growing anterior palatal lesion. Imaging
      reveals a well-circumscribed cystic lesion. Complete excision should be curative.
      Management requires attention to the potential need for palatal reconstruction,
      orthodontic care and correction of secondary nasal deformities.

PMID- 10906525
TI  - Pope John Paul II's address to the International Conference on Nutrition:
      introductory remarks.

PMID- 10906526
TI  - Pope John Paul II's address to the ICN.

PMID- 10906527
TI  - Comment from the editors

PMID- 10906528
TI  - Oxygen: the air-borne nutrient that both sustains and threatens life.

PMID- 10906529
TI  - Back to basics: why foods of wild primates have relevance for modern human
      health.

PMID- 10906530
TI  - Natural and cultural influences on the evolution of the human diet: background of
      the multifactorial processes that shaped the eating habits of Western societies.

PMID- 10906531
TI  - Nutrition transition and global dietary trends.

PMID- 10906532
TI  - Old wine in new bottles? The RDA and the DRI.

PMID- 10906533
TI  - Nutriogenetics and child development in the 21st century.

PMID- 10906534
TI  - Nutrition in embryonic and fetal development.

PMID- 10906535
TI  - Placental nutrient transfer and fetal growth.

PMID- 10906536
TI  - Long-term functional consequences of malnutrition during brain development:
      copper.

PMID- 10906537
TI  - Nutrient deprivation and brain function: iron.

PMID- 10906538
TI  - Breast milk: a truly functional food.

PMID- 10906539
TI  - The emergence of boron as nutritionally important throughout the life cycle.

PMID- 10906540
TI  - Calcium and magnesium requirements of children and adolescents and peak bone
      mass.

PMID- 10906541
TI  - Brain function, mind, mood, nutrition, and physical exercise.

PMID- 10906542
TI  - Exercise, appetite control, and energy balance.

PMID- 10906543
TI  - Caffeine and nutrition.

PMID- 10906544
TI  - Progress and plans regarding the nutritional status of smoking adolescents.

PMID- 10906545
TI  - From research to education: the Greek experience.

PMID- 10906546
TI  - Health benefits of a vegetarian diet.

PMID- 10906547
TI  - Food and nutrition in space: application to human health.

PMID- 10906548
TI  - Nutrition and senescence: healthy aging for all in the new millennium?

PMID- 10906549
TI  - SENECA's accomplishments and challenges.

PMID- 10906550
TI  - Nutrition and depression: focus on folate.

PMID- 10906551
TI  - Eating disorders: diagnosis, etiology, and prevention.

PMID- 10906552
TI  - Risk characterization of the potential for human health impact from environmental
      concentrations of endocrine modulators.

PMID- 10906553
TI  - Prion diseases.

PMID- 10906554
TI  - Malnutrition: causes, consequences, and solutions.

PMID- 10906555
TI  - Is fiber protective against colon cancer? Where the research is leading us.

PMID- 10906556
TI  - Nutrition and cancer: ten lessons from the 20th century.

PMID- 10906557
TI  - Dietary considerations to prevent loss of bone and renal function.

PMID- 10906558
TI  - An overview of nutritional issues for the adult with cystic fibrosis.

PMID- 10906559
TI  - The role of nutrients in the prevention of cervical dysplasia and cancer.

PMID- 10906560
TI  - Vitamin A and cancer.

PMID- 10906561
TI  - Carotenoids and gene expression.

PMID- 10906562
TI  - Dietary antioxidants and assessment of oxidative stress.

PMID- 10906565
TI  - Malnutrition, disease, and outcome.

PMID- 10906563
TI  - Recalling a 63-year nutrition odyssey.

PMID- 10906564
TI  - Nutritional assessment.

PMID- 10906566
TI  - The role of antioxidants in nutritional support.

PMID- 10906567
TI  - Intravenous containers and solution packaging.

PMID- 10906568
TI  - The effect of the administration of nucleosides and nucleotides for parenteral
      use.

PMID- 10906570
TI  - Enteral versus parenteral nutrition: the significance of bacterial translocation
      and gut-barrier function.

PMID- 10906569
TI  - Amino-acid substrates in new bottles: implications for clinical nutrition in the
      21st century.

PMID- 10906572
TI  - Pharmaceutical aspects of parenteral nutrition: from now to the future.

PMID- 10906571
TI  - Bacteria for optimal health.

PMID- 10906574
TI  - Nutrition and rehabilitation after discharge from the hospital: accelerating the
      rehabilitation with nutrition and physical training.

PMID- 10906573
TI  - The future for the patient with severe short gut syndrome.

PMID- 10906575
TI  - Education in artificial nutrition: the Indian experience.

PMID- 10906577
TI  - Transitional changes in health-disease: why so many puzzling epidemiological
      situations?

PMID- 10906576
TI  - A global perspective of home parenteral and enteral nutrition.

PMID- 10906578
TI  - Food agencies and food standards: the future regulatory mechanism for the food
      trade?

PMID- 10906580
TI  - Improving public awareness of nutrition issues.

PMID- 10906579
TI  - Multiple approaches and partnerships in public-health nutrition interventions.

PMID- 10906581
TI  - A decade of the United Nations' Convention on the Rights of the Child:
      implications for child nutrition and for the conceptualization of norms and
      interventions in public-health nutrition.

PMID- 10906582
TI  - From kwashiorkor to chronic pluricarential syndrome.

PMID- 10906583
TI  - Nutrition communication in the 21st century: what are the challenges and how can
      we meet them?

PMID- 10906584
TI  - Reducing foodborne disease: what are the priorities?

PMID- 10906585
TI  - Role of nutrition in primary care.

PMID- 10906586
TI  - Hunger in the United States: policy implications.

PMID- 10906587
TI  - Overview of naturally occurring endocrine-active substances in the human diet in
      relation to human health.

PMID- 10906588
TI  - Potential endocrine-modulating effects of various phytoestrogens in the diet.

PMID- 10906589
TI  - High salt intake and cardiovascular disease: is there a connection?

PMID- 10906590
TI  - Lactose intolerance and irritable bowel syndrome.

PMID- 10906591
TI  - The gut and amino acid homeostasis.

PMID- 10906592
TI  - Choline: an essential nutrient for humans.

PMID- 10906593
TI  - Homocysteine as atherothrombotic agent: is the bark worse than the bite?

PMID- 10906594
TI  - Homocysteine, Alzheimer's disease, and cognitive function.

PMID- 10906595
TI  - Chicory fructooligosaccharides and the gastrointestinal tract.

PMID- 10906596
TI  - Marine oils: the health benefits of n-3 fatty acids.

PMID- 10906597
TI  - Cranberry juice and urinary-tract health: science supports folklore.

PMID- 10906598
TI  - Nutraceuticals and functional foods: introduction and meaning.

PMID- 10906599
TI  - A European consensus of scientific concepts of functional foods.

PMID- 10906600
TI  - Antioxidant polyphenols in tea, cocoa, and wine.

PMID- 10906601
TI  - Functional properties of edible mushrooms.

PMID- 10906602
TI  - Functional food and contemporary nutrition-health paradigm: tempeh and its
      potential beneficial effects in disease prevention and treatment.

PMID- 10906603
TI  - Food irradiation.

PMID- 10906605
TI  - Outlook for consumer acceptance of agricultural biotechnology.

PMID- 10906604
TI  - Enrichment of food staples through plant breeding: a new strategy for fighting
      micronutrient malnutrition.

PMID- 10906606
TI  - Labeling of gene-spliced foods: a label we don't need.

PMID- 10906607
TI  - Food risks from transgenic crops in perspective.

PMID- 10906608
TI  - Bioactive proteins and probiotic bacteria: modulators of nutritional health.

PMID- 10906611
TI  - Knowledge-based information management in intensive care and anesthesia

PMID- 10906609
TI  - Differential PCR and DNA microarrays: the modern era of nutritional
      investigations.

PMID- 10906610
TI  - The role of free radicals and antioxidants.

PMID- 10906612
TI  - Multiple signal integration by decision tree induction to detect artifacts in the
      neonatal intensive care unit.
AB  - The high incidence of false alarms in the intensive care unit (ICU) necessitates
      the development of improved alarming techniques. This study aimed to detect
      artifact patterns across multiple physiologic data signals from a neonatal ICU
      using decision tree induction. Approximately 200 h of bedside data were analyzed.
      Artifacts in the data streams were visually located and annotated retrospectively
      by an experienced clinician. Derived values were calculated for successively
      overlapping time intervals of raw values, and then used as feature attributes for
      the induction of models trying to classify 'artifact' versus 'not artifact'
      cases. The results are very promising, indicating that integration of multiple
      signals by applying a classification system to sets of values derived from
      physiologic data streams may be a viable approach to detecting artifacts in
      neonatal ICU data.

PMID- 10906613
TI  - Towards symbolization using data-driven extraction of local trends for ICU
      monitoring.
AB  - We propose a methodology for the extraction of local trends from a stream of
      data. It has been designed to suit the needs of interpretation-oriented
      visualization and symbolization from ICU monitoring data. After giving
      implementation details for efficient computation of local trends, we propose the
      use of a characteristic analysis span for each variable. This characteristic span
      is obtained from a set of criteria that we compare and evaluate in regard of
      analysis of ICU monitoring data gathered within the Aiddaig project. The
      processing results in a rich visual representation and a framework for the local
      symbolization of the data stream based on its dynamics.

PMID- 10906614
TI  - Knowledge discovery and knowledge validation in intensive care.
AB  - Operational protocols are a valuable means for quality control. However,
      developing operational protocols is a highly complex and costly task. We present
      an integrated approach involving both intelligent data analysis and knowledge
      acquisition from experts that support the development of operational protocols.
      The aim is to ensure high quality standards for the protocol through empirical
      validation during the development, as well as lower development cost through the
      use of machine learning and statistical techniques. We demonstrate our approach
      of integrating expert knowledge with data driven techniques based on our effort
      to develop an operational protocol for the hemodynamic system.

PMID- 10906616
TI  - Vascular biology working group: the canadian initiative - issues of emerging
      interest

PMID- 10906615
TI  - A probabilistic and decision-theoretic approach to the management of infectious
      disease at the ICU.
AB  - The medical community is presently in a state of transition from a situation
      dominated by the paper medical record to a future situation where all patient
      data will be available on-line by an electronic clinical information system. In
      data-intensive clinical environments, such as intensive care units (ICUs),
      clinical patient data are already fully managed by such systems in a number of
      hospitals. However, providing facilities for storing and retrieving patient data
      to clinicians is not enough; clinical information systems should also offer
      facilities to assist clinicians in dealing with hard clinical problems. Extending
      an information system's capabilities by integrating it with a decision-support
      system may be a solution. In this paper, we describe the development of a
      probabilistic and decision-theoretic system that aims to assist clinicians in
      diagnosing and treating patients with pneumonia in the intensive-care unit. Its
      underlying probabilistic-network model includes temporal knowledge to diagnose
      pneumonia on the basis of the likelihood of laryngotracheobronchial-tree
      colonisation by pathogens, and symptoms and signs actually present in the
      patient. Optimal antimicrobial therapy is selected by balancing the expected
      efficacy of treatment, which is related to the likelihood of particular pathogens
      causing the infection, against the spectrum of antimicrobial treatment. The
      models were built on the basis of expert knowledge. The patient data that were
      available were of limited value in the initial construction of the models because
      of problems of incompleteness. In particular, detailed temporal information was
      missing. By means of a number of different techniques, among others from the
      theory of linear programming, these data have been used to check the
      probabilistic information elicited from infectious-disease experts. The results
      of an evaluation of a number of slightly different models using retrospective
      patient data are discussed as well.

PMID- 10906618
TI  - Estrogens should not be initiated for the secondary prevention of coronary artery
      disease: a debate.
AB  - Randomized controlled clinical trials investigating disease outcomes provide the
      best evidence to guide clinical practice. In the case of coronary artery disease
      (CAD), the only major clinical trial that has been completed does not support the
      epidemiological and pathophysiological evidence that estrogen is a
      cardioprotective agent. In the Heart and Estrogen/progestin Replacement Study
      (HERS), hormone replacement therapy (HRT) was of no overall benefit in the
      secondary prevention of CAD events in postmenopausal women. In addition, HRT was
      associated with a threefold increase in thromboembolic events. Based on the
      clinical trial evidence, estrogen therapy should not be initiated for the
      secondary prevention of CAD.

PMID- 10906617
TI  - Role of estrogens, selective estrogen receptor modulators and phytoestrogens in
      cardiovascular protection.
AB  - A large body of evidence suggests that estrogen may be of benefit in reducing the
      risk of heart disease in postmenopausal women. The mechanism by which this
      benefit is conferred has been the subject of numerous investigations. In addition
      to the well known effects of estrogen on lipids, estrogen exerts a number of
      endothelium-dependent effects related to both vasodilation and nitric oxide
      metabolism that may have a favourable impact on vascular health. However, this
      benefit has not yet been confirmed in randomized clinical trials. Indeed, the
      only large trial published to date failed to document a benefit in women with
      established heart disease. Recent studies have shown that estrogen may also have
      some prothrombotic or proinflammatory effects that may offset other benefits. The
      extent to which selective estrogen receptor modulators and phytoestrogens share
      in the beneficial and potentially harmful effects of estrogen is not yet
      established.

PMID- 10906619
TI  - Estrogens are indicated for the prevention of coronary artery disease: a debate
      for estrogen.
AB  - For the vast majority of women, the overall potential benefits associated with
      hormone replacement therapy (HRT) outweigh any harm. There is a large body of
      epidemiological evidence demonstrating an association between postmenopausal use
      of HRT and a decreased risk for cardiovascular disease. There are multiple
      mechanisms by which this cardiovascular benefit may occur. The only study to
      suggest that estrogen does not play a cardioprotective role was conducted on
      women with known coronary artery disease, ie, secondary prevention. The results
      of this study may be specific to the population and the regimen studied; in any
      case, several confounding factors limit the interpretation of the data. If these
      factors are adequately addressed in future trials, it is probable that the
      cardiovascular benefits of HRT will be clinically evident.

PMID- 10906620
TI  - Mechanism of the deadly quartet.
AB  - A deadly quartet of risk factors places diabetics at a particularly high risk for
      adverse cardiovascular events; these factors are hypertension, hyperlipidemia,
      hyperglycemia and hyperinsulinemia. A number of metabolic abnormalities are
      common to diabetes. Many of them, including dyslipidemia, have been linked to
      both insulin resistance and endothelial dysfunction. Several lines of evidence
      have led to the hypothesis that insulin resistance may be a key
      pathophysiological mechanism leading to endothelial dysfunction and
      atherosclerosis in patients with diabetes and possibly other illnesses. In both
      diabetic and nondiabetic populations, the common risk factors for coronary artery
      disease events are dyslipidemia, insulin resistance, obesity and high blood
      pressure. A number of strategies are recommended to prevent the potentially
      deadly consequences of these factors.

PMID- 10906621
TI  - Case 1. Cardiovascular dysfunction syndrome.
AB  - A 56-year-old woman is referred with angina. A number of sequential management
      strategies have been attempted with varying results. Upon examination of her
      case, it is clear that she has cardiovascular dysmetabolic syndrome and is thus
      at high risk for adverse cardiovascular events. Two opinions for further
      management are presented.

PMID- 10906622
TI  - Case 2. Recurrence of myocardial infarction.
AB  - A 50-year-old man arrives in the emergency room with signs and symptoms occurring
      intermittently over a period of 48 h consistent with a myocardial infarction. He
      has several major risk factors for a recurrent event. A number of management
      strategies have already been attempted. Two opinions for further management are
      presented.

PMID- 10906623
TI  - Systemic and nontraditional markers of endothelial dysfunction.
AB  - Endothelial cells control the balance between a number of opposing biological
      processes. Injury to these cells leads to a shift in this delicate balance; the
      resultant endothelial dysfunction ultimately leads to atherosclerotic disease.
      Specific markers of endothelial dysfunction can be used to detect and monitor the
      progression of atherosclerosis; they can also be used to study the pathogenesis
      of disease. Specific markers may be indicative of a particular stage in the
      pathogenesis of disease. By using a rigorous screening process, various markers
      of endothelial dysfunction can be identified. Common markers of endothelial
      dysfunction that are used in clinical studies are vascular cell adhesion molecule
      1, intracellular adhesion molecule-1 and fibrinogen.

PMID- 10906624
TI  - Clinical data: AVERT and QUO VADIS.
AB  - Various clinical studies have been undertaken to assess whether medical
      interventions are effective for the prevention of cardiovascular events in
      patients with coronary artery disease. In the Angioplasty Compared with MEdical
      therapy (ACME) and Randomized Intervention Treatment of Angina 2 (RITA-2)
      studies, a medical strategy was associated with significantly fewer adverse
      cardiovascular events, but percutaneous revascularization was associated with
      greater functional improvement. In the Atorvastatin VErsus Revascularization
      Treatment (AVERT) study, aggressive lipid-lowering therapy with atorvastatin was
      more effective than angioplasty at reducing the total number of ischemic events;
      however, angioplasty was superior in terms of functional improvements. Thus, to
      prevent ischemic events in this population, coronary artery disease is best
      treated systemically; if better symptom control is required, angioplasty is still
      necessary. In the effects of QUinapril On Vascular ACE and Determinants of
      ISchemia (QUO VADIS) study, treatment with the angiotensin-converting enzyme
      (ACE) inhibitor quinapril was associated with significantly fewer ischemic events
      than placebo at one year following coronary artery bypass graft surgery. However,
      no significant differences were found between treatments in terms of primary and
      other secondary outcomes. For patients who have undergone bypass surgery, long
      term ACE inhibitor therapy may be of benefit, although further studies are
      warranted.

PMID- 10906625
TI  - Pharmacology of ACE inhibitors versus AT1 blockers.
AB  - Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1)
      receptor blockers share a number of common properties, including their ability to
      lower blood pressure. However, they can be differentiated based on their
      individual effects on the renin-angiotensin system, the fibrinolytic system and
      the actions of bradykinin. They act at different points in the cascade of events
      that constitute the renin-angiotensin system. In animal models of
      atherosclerosis, ACE inhibition was associated with a significant reduction in
      the percentage surface area of lesions, while no similar effect was evident with
      AT1 receptor blockade. In the fibrinolytic system, both ACE inhibition and AT1
      receptor blockade were associated with reduced aldosterone levels, although the
      effect was greater with ACE inhibition; only ACE inhibition was associated with a
      significant reduction in plasminogen activation inhibitor-1. By blocking the
      degradation of bradykinin, ACE inhibitors potentiate the ability of bradykinin to
      reduce blood pressure and stimulate the release of tissue-type plasminogen
      activator from the vasculature, an effect not seen with AT1 receptor blockers.

PMID- 10906626
TI  - ACE inhibitors versus AT1 blockers in the treatment of hypertension and syndrome
      X.
AB  - Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1)
      receptor blockers are two separate classes of drugs. Although they are both
      effective antihypertensive agents, they exert their effects through different
      pharmacological mechanisms. Nonetheless, they have often proved indistinguishable
      in terms of the surrogate endpoints used in short term clinical studies.
      Considerable data are available on the long term benefits of ACE inhibition;
      however, studies looking at the long term effects of AT1 receptor blockade are
      not yet complete. If ACE inhibitors prove to be distinguishable from AT1 receptor
      blockers in terms of disease-related outcomes, the reason may be the selective
      effects of ACE inhibitors on insulin resistance and insulin-mediated vascular
      function.

PMID- 10906628
TI  - [An overwhelming passion. Address of the chairman].

PMID- 10906629
TI  - [2000, the year of vascular medicine? address of the general secretary] [In
      Process Citation]

PMID- 10906630
TI  - [Graduation of honorary members] [In Process Citation]

PMID- 10906631
TI  - [Systemic vasculitis].
AB  - Systemic vasculitis is a general term designating a wide range of sometimes
      overlapping vascular conditions with marked tropism for peripheral constituting a
      complex nosological structure. Angiologists must be aware of the different
      telltale clinical signs including purpura, polyarthritis, glomerulonephritis,
      polyneuritis and unexplained inflammatory syndrome. Medium-sized and small-sized
      vessels are involved in a wide range of visceral damage. Several typical clinical
      presentations have led to the individualization of recognized syndromes such as
      rheumatoid type purpura, Wegener disease, Churg disease, Strauss disease, or peri
      arteritis nodosa. Anti-nuclear serologies (pANCA and cANCA) contribute to
      diagnosis and have been helpful in individualizing a new entity: microscopic
      polyangeitis. In angiological practice, macroscopic expression of systemic
      vasculitis can lead to Takayasu type granulomatous angeitis in yong women and
      giant-cell arteritis in the elderly. These different arteriopathies should be
      treated by corticosteroid therapy with regular laboratory tests to follow
      inflammation and angiograhic exploration in case of occlusive arterial
      complications. Although these conditions are quite rare, a better understanding
      of their pathogenesis and their clinical course should help the angiologist make
      the initial diagnosis and the therapist to monitor treatment efficacy.

PMID- 10906633
TI  - [Determination of polymorphonuclear neutrophil adhesion receptors. Effect of pre
      analytic factors].
AB  - Polymorphonuclear neutrophil (PMN) adherence receptors expression varies with
      leukocyte activation state. Their quantification need accurate and inter
      laboratories reproducible methods, without artefactual activation. OBJECTIVE: The
      aim of this study was to study the influence of cell preparation on PMN adherence
      receptors expression. MATERIALS AND METHODS: It was proposed to quantify, using
      immunolabeling standard (QIFIKIT(R), Dako), surface expression of the main
      adherence receptors (L-selectin and B(2) integrins), from different preparations
      of PMN: total blood collected with EDTA, isolated PMN by density gradient
      Polymorphprep(TM) 1,113 (Nycomed Pharma) and formaldehyde fixed PMN. RESULTS: A
      decrease of all receptors was noted after isolation and fixation of PMN, in
      comparison with whole blood PMN analysis. These results differed from data
      previously reported since, in these studies, activated phenotypes (increased of
      B(2) integrins) were observed after isolation and fixation methods. CONCLUSION:
      The present study provides strong evidence that pre-analytical conditions are
      sources of biological variations and thus extreme care must be taken in the
      interpretation of results. It underlines the interest of consensual practices for
      these pre-analytic and analytic parameters in order to compare results in
      multicenter and longitudinal studies.

PMID- 10906632
TI  - [Electrophysiological diagnosis of neurogenic thoracic outlet syndrome].
AB  - The neurogenic thoracic outlet syndrome includes the symptoms caused by the
      compression of the brachial plexus at some point between the interscalene
      triangle and the inferior border of the axilla. Five patients diagnosed as having
      neurogenic thoracic outlet syndrome were examined. We determinated clinical and
      electrophysiological features which lead to thoracic outlet syndrome diagnosis.
      The clinical features included paresthesia and pain along the inner part of the
      arm, forearm and hand. Diminished sensation was rare. Muscle weakness was usual
      and muscle atrophy was associated in severe cases. The association with a lower
      cervical rib was useful. Electrodiagnostic studies always showed abnormalities.
      Electromyographic studies showed a reduced recruitment pattern of motor unit
      activation in intrinsic hand muscles. The medial antebrachial cutaneous nerve
      action potential amplitude was low. Nerve conduction studies also showed loss of
      amplitude of the ulnar sensory and median motor responses.

PMID- 10906634
TI  - [Survey on adherence to hygiene and dietary rules in patients with arterial
      occlusive disease].
AB  - OBJECTIVE: Chronic arterial occlusive disease of the lower limbs, a common
      (800,000 patients in France) invalidating condition, can involve one or more
      arterial territories. In 90% of the cases, it is related to a more general
      disease, atherosclerosis. The risk factors are the same as for atherosclerosis
      and can be classed into three distinct groups: pathological conditions,
      constitutional characteristics, and lifestyle. Besides age and gender, smoking
      habits are by far the most predominant vascular risk factor for chronic arterial
      occlusive disease. Other factors include diabetes, known to play a particular
      role in diabetic arteriopathy, generally with more distal and quite severe
      lesions, high blood pressure, a less evident but certain risk factor, and
      hyperlipidemia, whole role in the pathogenesis of chronic arterial occlusive
      disease is well recognized though not predominant. These different data led us to
      analyze a cohort of patients with chronic arterial occlusive disease of the lower
      limbs to ascertain the cause of success or failure of hygiene and diet
      counseling. PATIENTS AND METHODS: The study protocol included three steps. We
      first established the profile of a typical arteriopathy patient based on
      demographic data, history of the arterial disease, personal and familial medical
      history and lifestyle: smoking habits, physical exercise, diet. The second step
      was to estimate the proportion of patients following hygiene and dietary rules.
      Finally, we looked for the reasons why the patients succeeded or failed in
      following these rules. This cross-sectional study involved 1,500 practitioners.
      Each physician selected 3 patients, men or women aged 40 to 80 years whose
      arteriopathy had reached the stage of intermittent claudication. Evaluation
      criteria were based on the demographic data and conditions of adherence to advice
      as well as conditions leading to success or failure: personal motivation,
      familial support, the patient's knowledge of the disease, its pathophysiological
      mechanisms, and the way the risk factors contribute to its genesis and
      aggravation. RESULTS: The sex ratio of the 3,294 recruited patients was 4.3
      (2,672 men and 622 women). Disease duration and walking distance were 8.6 +/- 6
      years and 418 +/- 297 meters respectively. Thirty-eight percent of the patients
      had undergone surgery of the lower limbs. One thousand four hundred ninety-four
      patients (45%) had undergone surgery for their arterial disease (lower limbs,
      coronary or cerebral arteries). Forty-nine percent were aware of the risk of
      amputation. Overall adherence to drug therapy was good for 82% of the patients.
      Patients were treated basically with vasoactive and platelet antiaggregates (95
      and 82% of the patients respectively). Seventy-nine percent of the patients were
      former smokers (38% continued to smoke). Fifty-six percent had a specific regular
      physical activity compared with 42% prior to their disease. Seventeen percent of
      the patients had already tried a Mediterranean type diet (with a success rate of
      69%). Among the 3, 294 patients, 950 (28.8%) followed hygiene and dietary rules
      well. The main reasons and/or conditions differentiating those who were
      successful and those who were not were, for each item: personal motivation,
      family support, and perception of the influence of lifestyle on disease course.
      These differences were highly significant (p <0.001). CONCLUSION: Considering the
      importance of following good hygiene and dietary rules for secondary prevention
      of chronic arterial occlusive disease of the lower limbs, it was interesting to
      assess with precision the percentage of diseased patients who follow such rules.
      Only about 30% of the patients were successful in correcting all behaviors.

PMID- 10906635
TI  - [Inflammatory abdominal aortic aneurysm. Role of corticosteroid therapy].
AB  - For more than 20 years it has been generally acknowledged that operation for
      inflammatory abdominal aortic aneurysm (IAAA) using the common in-lay-graft
      procedure will induce the regression of peri-aortic fibrosis. However in
      prospective studies, after a 2 years follow-up, no regression appeared in
      approximated 8% of the cases (table I). Moreover in some IAAA a corticosteroid
      treatment (CS) was prescribed and it produced a regression of fibrosis and
      therefore facilitated the operation. Nevertheless the usefulness of the CS
      remains debated. We report 4 new cases of IAAA with CS. Based on our cases and an
      analysis of the literature we conclude that when there is no urgency to operate
      (diameter inferior to 50 mm) CS is the best option in IAAA with either severe
      inflammation or ureter involvement. Due to the regression of the fibrosis it can
      facilitate the surgical procedure. However it needs to be conducted with an
      adequate dose and duration. Finally the CS is the only possibility when the
      inflammation persist following the treatment of the IAAA.

PMID- 10906636
TI  - [Allen's test. 1929].

PMID- 10906637
TI  - Advances in specific immunotherapy of malignant melanoma.
AB  - Management of malignant melanoma continues to present a challenge to
      dermatologists, particularly in advanced cases. In light of the steady increase
      in the worldwide incidence and mortality rates for melanoma, better understanding
      of the immune mechanisms regulating melanoma progression and interaction with the
      host's immune system seems eminently important. New studies on the role of immune
      mechanisms in the pathogenesis and clinical course of melanoma have recently been
      published. We review the immune mechanisms involved in tumor progression and ways
      in which these mechanisms may be applied toward immunotherapeutic management of
      malignant melanoma. LEARNING OBJECTIVE: After the completion of this learning
      activity, participants should be familiar with (1) the immune mechanisms involved
      in host-tumor interaction and tumor rejection, (2) factors allowing the escape of
      melanoma cells from immune recognition, and (3) the current rationale for the
      different types of specific immunotherapy in melanoma. Better understanding of
      basic mechanisms in tumor immunology should raise awareness of future
      immunotherapeutic approaches in patients with melanoma, particularly in those who
      are at high risk of recurrence or who present with advanced disease.

PMID- 10906638
TI  - Autosomal dominantly inherited generalized basaloid follicular hamartoma
      syndrome: report of a new disease in a North Carolina family.
AB  - BACKGROUND: An 8-year-old girl presented with hundreds of milia, measuring 1 to 2
      mm; comedone-like lesions; skin-colored and hyperpigmented papules on the face,
      scalp, ears, neck, upper trunk, and lower arms along with diffuse scalp
      hypotrichosis; and pinpoint palm/sole pits. Onset was in early childhood and the
      disease was historically present in 6 generations. OBJECTIVE: Our objectives were
      to delineate the clinical and histopathologic features and mode of inheritance as
      a base for gene studies. METHODS: Eighteen family subjects were studied. Twenty
      six skin biopsy specimens were examined. A detailed pedigree was constructed. A
      complete literature search was done concerning diseases with generalized basaloid
      follicular hamartomas. RESULTS: The lesions were basaloid follicular hamartomas
      and other folliculocentric abnormalities. Inheritance was autosomal dominant.
      Extensive literature search confirmed the finding of a unique genodermatosis.
      CONCLUSION: A new genodermatosis termed dominantly inherited generalized basaloid
      follicular hamartoma syndrome was defined by delineating its clinical and
      histopathologic features and mode of inheritance and by extensive literature
      review.

PMID- 10906639
TI  - Adult-onset recalcitrant eczema: a marker of noncutaneous lymphoma or leukemia.
AB  - BACKGROUND: Generalized eczema or erythroderma may be the presenting sign of
      cutaneous T-cell lymphoma. Additionally, intractable pruritus has been associated
      with Hodgkin's lymphoma. However, reports of adult-onset eczematous dermatitis
      has rarely been linked to noncutaneous lymphoproliferative disorders.
      OBSERVATIONS: We observed one patient in 1993 who had the onset of intractable
      dermatitis characterized by prurigo nodularis-like lesions and widespread
      erythematous plaques. After 18 months of cutaneous symptoms he experienced
      dyspnea. At this time Hodgkin's disease was diagnosed. This observation prompted
      us to evaluate subsequent patients with adult-onset eczema who were poorly
      responsive to therapy and in whom an obvious cause could not be determined. Over
      the next 24 months we identified an additional 2 patients with lymphoma who met
      this criteria. CONCLUSION: Unexplained eczema of adult onset may be associated
      with an underlying lymphoproliferative malignancy. When a readily identifiable
      cause (eg, contactants, drugs, or atopy) is not found, a systematic evaluation
      should be pursued. Patients should be evaluated with a careful physical
      examination, complete blood cell counts, peripheral blood smears, chest
      roentgenography, computed tomography of the chest and abdomen, and serum protein
      electrophoresis.

PMID- 10906640
TI  - Increasing supplies of dermatologists and family physicians are associated with
      earlier stage of melanoma detection.
AB  - BACKGROUND: Physicians are important in the early detection of melanoma. We
      investigated whether primary care physician supply and the supply of
      dermatologists were related to stage at diagnosis for malignant melanoma.
      METHODS: From the state tumor registry in Florida in 1994, we identified incident
      cases of malignant melanoma for which stage at diagnosis was available (N =
      1884). Data on physician supply was obtained from the 1994 American Medical
      Association Physician Masterfile. Logistic regression determined the effects of
      physician supply (at the ZIP code level) on the odds of early-stage diagnosis
      controlling for patients' age, gender, race/ethnicity, marital status, education
      level, income level, comorbidity, and type of health insurance. RESULTS: Each
      additional dermatologist per 10,000 population was associated with a 39%
      increased odds of early diagnosis (odds ratio = 1.39, 95% confidence interval
      [CI] 1.09-1.70, P =.010). For each additional family physician per 10,000
      population, the odds of early diagnosis increased 21% (odds ratio = 1.21, 95% CI
      1.09-1.33, P <.001). Each additional general internist per 10,000 population was
      associated with a 10% decrease in the odds of early-stage diagnosis (odds ratio =
      0.90, 95% CI 0.83-0.98, P =.009). The supplies of general practitioners,
      obstetrician/gynecologists, and other nonprimary care specialists were not
      associated with stage at diagnosis. CONCLUSIONS: Increasing supplies of
      dermatologists and family physicians were associated with earlier detection of
      melanoma. In contrast, increasing supplies of general internists were associated
      with reduced odds of early detection. Our findings suggest that the composition
      of the physician work force may affect important health outcomes and needs
      further study.

PMID- 10906641
TI  - The effect of sunscreen on the efficacy of insect repellent: a clinical trial.
AB  - Sunscreen loses efficacy when used with the insect repellent N,N -diethyl-3
      methylbenzamide (diethyltoluamide; deet). A previous study demonstrated a 33.3%
      decrease in sun protection factor when insect repellent and sunscreen were
      applied sequentially to the skin. The purpose of this study was to determine
      whether the efficacy of insect repellent is affected by two different
      formulations of sunscreen. The combination of sunscreen and insect repellent was
      tested in 8 groups: a control group (no sunscreen or insect repellent), sunscreen
      alone (two groups [gel and cream]), insect repellent alone, insect repellent
      applied before sunscreen (two groups), and insect repellent applied after
      sunscreen (two groups). The results of this study showed that insect repellent
      has the same efficacy even when sunscreen is applied with it. This indicates that
      in the formulations tested, sunscreen does not reduce the efficacy of insect
      repellent.

PMID- 10906642
TI  - Armadillo exposure and Hansen's disease: an epidemiologic survey in southern
      Texas.
AB  - BACKGROUND: Naturally occurring leprosy has been demonstrated in wild nine-banded
      armadillos (Dasypus novemcinctus ). This suggests a possible mode of transmission
      of human leprosy in regions where armadillo contact is prevalent. OBJECTIVE: Our
      purpose was to study the possible relationship between armadillo exposure and
      Hansen's disease. METHOD: One hundred one patients (67 men, 34 women) with
      established Hansen's disease seen in the Hansen's Disease Clinic in Houston,
      Texas, were questioned about their exposure to armadillos. These patients were
      divided into two groups: Asian (n = 32) and non-Asian (n = 69). RESULTS: Seventy
      one percent of the non-Asian patients surveyed reported either direct or indirect
      armadillo exposure. None of the Asian patients reported armadillo exposure (P
      <.001). Of the non-Asian patients, 75.4% had lepromatous disease versus 50.0% of
      the Asian patients (P <.001). The average age at diagnosis for the non-Asian
      group with Hansen's disease in this study was 51 versus 38 years for the Asian
      group (P <.001). CONCLUSION: Although it is yet to be determined whether direct
      transmission from the armadillo to human occurs, it is likely based on the high
      incidence of armadillo exposure in non-Asian patients with Hansen's disease in
      our study population that this animal acts as a reservoir for human disease.
      However, the Asian patients reporting no known armadillo exposure likely obtained
      the disease from person-to-person contact in their respective countries of origin
      where Hansen's disease has a much higher prevalence.

PMID- 10906643
TI  - Measuring quality of life in people referred for specialist care of acne:
      comparing generic and disease-specific measures.
AB  - OBJECTIVE: Our purpose was to compare 3 approaches to the measurement of quality
      of life in patients referred for specialist care of acne. METHODS: A
      questionnaire was sent to 130 patients referred for management of their acne.
      Follow-up questionnaires were sent 4 and 12 months after treatment began. The
      questionnaire contained a generic index measure (EuroQol EQ-5D), a generic
      profile measure (Short Form 36), and a disease-specific measure (Dermatology Life
      Quality Index). Pretreatment results for the EQ-5D were compared with normative
      data. The responsiveness of the EQ-5D was compared with that of the other
      measures. RESULTS: Before treatment, the sample reported substantially more
      pain/discomfort and anxiety/depression on the EQ-5D compared with a population
      sample. The disease-specific measure was more responsive to change compared with
      both generic measures. CONCLUSION: Our study highlights the importance of
      combining information from generic measures with information from instruments
      designed specifically for use in people with skin disease.

PMID- 10906644
TI  - Skin examinations and skin cancer prevention counseling by US physicians: a long
      way to go.
AB  - BACKGROUND: Nonmelanoma skin cancer and actinic keratoses may be partially
      preventable by physician counseling. OBJECTIVE: The purpose of this study was to
      assess the frequency of counseling for skin cancer prevention. METHODS: Data on
      skin cancer counseling and skin examinations were obtained from representative
      visits to outpatient physicians in the United States from the 1997 National
      Ambulatory Medical Care Survey. A limitation of the skin examination data is that
      the extent of the skin examination was not reported. RESULTS: Skin examinations
      occurred in 60 million (8.6%) of 703 million office visits, and skin cancer
      prevention counseling or education occurred in 12 million visits (1.5%). For
      patients younger than 20 years, such prevention counseling occurred in only 1.0%
      of 169 million visits. For those patients with a current or previous history of
      nonmelanoma or melanoma skin cancer or actinic keratosis (high-risk patients)
      identified by the treating physician, 2.8 million (35%) of 7.9 million patients
      received such counseling. In high-risk patients, dermatologists provided such
      counseling at 41% of visits, compared with 24% for general and family practice,
      9.3% for otolaryngology, 13% for general surgery, and 7.7% for internal medicine.
      In such high-risk patients, skin examinations were performed at 78% of
      dermatology visits, 69% of otolarynogolgy visits, 36% of general surgery visits,
      and 27% of family physician visits. Capitation did not lead to greater primary
      preventive practices; skin cancer prevention counseling occurred in 4% of high
      risk capitated patients compared with 38% of noncapitated patients. CONCLUSION:
      Physicians provide skin cancer prevention counseling or education at fewer than
      half of visits for high-risk patients. High-risk patients are likely to receive
      skin cancer prevention messages depending on the specialty of physician that they
      visit in roughly the following scheme: dermatologists>family physicians>all other
      specialties. Economic restraints within managed care systems may affect their
      "health maintenance" function.

PMID- 10906645
TI  - Effects of glycolic acid on light-induced skin pigmentation in Asian and
      caucasian subjects.
AB  - BACKGROUND: Topical use of alpha-hydroxy acid (AHA) may increase skin
      photosensitivity, as demonstrated by increased numbers of sunburst cells.
      However, effects of AHA on tanning have not been studied. OBJECTIVE: Our purpose
      was to study whether short-term use of glycolic acid hastens resolution of pre
      existing light-induced pigmentation and whether the skin becomes tan more easily
      in Asian and Caucasian subjects after such treatment. METHODS: Six Asian and six
      Caucasian volunteers received separate irradiations of UVB and UVA to both sides
      of the lower back. In a double-blind fashion, patients then applied a 10%
      glycolic acid gel, pH 3.52, to one side of the back, including the irradiated
      area, and the contralateral extensor forearms once daily for 7 days and then
      twice daily for 2 weeks. A placebo gel, pH 5.75, was applied to the opposite
      sides. The subjects returned for measurement of residual tanning with a
      colorimeter and received additional irradiation to forearms and a second site on
      the back. Resulting pigmentation was measured immediately after irradiation, at 2
      hours, and at 1 week. RESULTS: Increased UVB-induced skin tanning occurred on the
      forearm and the lower back in both races in areas pretreated with glycolic acid.
      UVA also caused increased tanning, but only on the extensor forearms in Asian
      subjects. Treatment with glycolic acid for 3 weeks had no effect on pre-existing
      light-induced pigmentation. CONCLUSION: Short-term topical treatment of glycolic
      acid caused an increase in UVB tanning as well as in UVA tanning in some
      subjects, even in the absence of overt irritation. The inclusion of UVB, and even
      UVA, sunscreen in AHA products may be warranted.

PMID- 10906646
TI  - Prevalence and epidemiology of onychomycosis in patients visiting physicians'
      offices: a multicenter canadian survey of 15,000 patients.
AB  - A prospective, multicenter study to determine the epidemiology of onychomycosis
      was performed in the offices of 3 dermatologists and 1 family physician in
      Ontario, Canada. In the sample of 15,000 patients, abnormal-appearing nails were
      observed in 2505 persons (16. 7%). There were 1199 patients (8%) with toenail or
      fingernail onychomycosis confirmed on mycologic examination, with 1137 patients
      (7.6%) who had only pedal onychomycosis, 40 patients with toenail and fingernail
      onychomycosis (0.27%), and 22 patients (0.15%) with only fingernail
      onychomycosis. The condition was more common in male patients (P <.0001) and
      older persons (P <.0001). The ratio of onychomycosis in toenails/fingernails was
      19:1. When onychomycosis was present in toenails, the ratio of distal/lateral
      subungual onychomycosis (DLSO) to white superficial onychomycosis to proximal
      subungual onychomycosis was 360:59:1. The extent of DLSO in toenails was mild (<
      or =25% nail involvement), moderate (26%-74% disease), and severe (> or =75% nail
      involvement) in 27.6%, 39.9%, and 32.5% of patients, respectively. After
      adjusting for the age and sex distribution of the general population, the
      projected rate of onychomycosis in Canada is 6.5% (95% confidence interval [CI],
      6. 1%-6.9%). The organisms causing toenail onychomycosis were 90.5% dermatophyte,
      7.8% nondermatophyte molds, and 1.7% Candida spp. The corresponding organisms
      causing fingernail onychomycosis were 70.8%, 0%, and 29.2%, respectively. In a
      large sample of 15,000 patients, abnormal-appearing nails were present in 17% of
      the sample with mycologic evidence of toenail or fingernail onychomycosis in 8%.
      The projected prevalence of onychomycosis in Canada is 6.5% (95% CI, 6. 1%-6.9%).

PMID- 10906647
TI  - Pharmacology of botulinum toxin.
AB  - BACKGROUND: Botulinum toxin has a well-defined role among dermatologists for the
      treatment of facial wrinkling, brow position, and palmar and axillary
      hyperhidrosis. OBJECTIVE: The purpose of this study is to educate dermatologists
      on the pharmacology of botulinum toxin. METHODS: A retrospective review of the
      literature on botulinum toxin from 1962 to the present was conducted. We examined
      the clinical applications of botulinum toxin, cholinergic neuromuscular
      transmission, the toxin's structure and molecular actions, drug and disease
      interactions at the neuromuscular junction, toxin assays, determinants of
      clinical response, and adverse side effects. RESULTS: Botulinum toxin blocks the
      release of acetylcholine from the presynaptic terminal of the neuromuscular
      junction. Several drugs and diseases interfere with the neuromuscular junction
      and the effects of botulinum toxin. The mouse bioassay, the most sensitive and
      specific measurement of toxin activity, is the gold standard for botulinum toxin
      detection and standardization. The major determinants of clinical response to
      treatment are the toxin preparation, individual patient's anatomy, dose and
      response relationships, length of toxin storage after reconstitution, and
      immunogenicity. To minimize potential antibody resistance, one should use the
      smallest effective dose, utilize treatment intervals of more than 3 months, and
      avoid booster injections. Uncommon adverse effects include ptosis, ectropion,
      diplopia, bruising, eyelid drooping, hematoma formation, and temporary headaches.
      CONCLUSION: Botulinum toxin is a safe and effective treatment. Knowledge of the
      pharmacologic basis of therapy will be useful for standardizing techniques and
      achieving consistent therapeutic results in the future.

PMID- 10906648
TI  - Oral metronidazole treatment of lichen planus.
AB  - BACKGROUND: Oral metronidazole has been reported to be effective in some patients
      with idiopathic lichen planus (LP) who did not have concomitant protozoal
      infections of the intestinal or genital tracts. OBJECTIVE: Our purpose was to
      evaluate the efficacy of this drug in the treatment of generalized LP. METHODS:
      Nineteen patients with LP who were free from intestinal and genital protozoal
      infections were treated with oral metronidazole, 500 mg twice daily, for 20 to 60
      days and were followed up for a period of 5 to 36 months. RESULTS: Fifteen
      patients (78.9%) improved with metronidazole treatment. Complete response was
      observed in 13 patients (7 women and 6 men). Two patients responded partially.
      Worsening of the lesions was observed in 1 of the 4 nonresponding patients.
      CONCLUSION: Metronidazole may be an alternative therapy for the treatment of
      generalized LP. Its immunomodulatory activity seems to be a possible mechanism of
      action besides its antimicrobial activity.

PMID- 10906649
TI  - Extracorporeal photochemotherapy alone or with adjuvant therapy in the treatment
      of cutaneous T-cell lymphoma: a 9-year retrospective study at a single
      institution.
AB  - BACKGROUND: Extracorporeal photochemotherapy (ECP; photopheresis) is a treatment
      option for cutaneous T-cell lymphoma (CTCL). OBJECTIVE: This study describes the
      outcomes obtained with ECP alone or with adjuvant therapy in treating CTCL.
      METHODS: A 9-year retrospective study was performed at a single institution.
      RESULTS: Among 69 patients, 37 were treated with 6 months or more of ECP alone
      over an average of 36.9 months. Of these patients, 68% (25/37) had stage T2, 5%
      (2/37) had stage T3, and 27% (10/37) had stage T4 CTCL. Complete response (no
      skin or systemic disease for 1 month or more) and partial response (50%-99% skin
      improvement for 1 month or more) were achieved by 14% (5/37) and 41% (15/37) of
      patients, respectively, giving an overall response rate of 54% (20/37). In
      recalcitrant patients, adjuvant therapy significantly increased the response rate
      from 31% (4/13) to 69% (9/13) (P = 0.004). ECP was well tolerated in the entire
      patient population. CONCLUSION: Response rates in this study compared favorably
      with those in previous studies, underscoring the potential value of ECP in
      treating CTCL. To our knowledge, this investigation included the largest group of
      CTCL patients ever treated with ECP at a single institution.

PMID- 10906650
TI  - Treatment of nonmelanotic hyperpigmentation with the Q-switched ruby laser.
AB  - Hyperpigmentation of the skin is often refractory to conventional therapies, but
      has significant cosmetic implications if located on visible areas. Because laser
      systems are capable of removing pigment deposits caused by selective
      photothermolysis, we addressed the issue of whether the Q-switched ruby laser
      could be a useful alternative in the treatment of nonmelanotic hyperpigmented
      skin lesions. We report the successful treatment of a patient with
      hyperpigmentation caused by iatrogenic human herpesvirus 8-associated Kaposi's
      sarcoma and a patient with hyperpigmentation caused by long-term antimalarial
      therapy for cutaneous lupus erythematosus. In both patients, clinical lightening
      of the darkly pigmented lesions was seen after a single treatment, and a
      significant improvement was observed after 3 laser applications. The patients
      tolerated the laser therapy well without any short-term side effects and did not
      experience either scarring or considerable textural skin changes. Histologic
      examination was performed before and after laser treatment to confirm the
      reduction of the pigment deposits. Our data indicate that treatment of
      nonmelanotic skin hyperpigmentation with the Q-switched ruby laser might be a
      safe and powerful therapeutic method.

PMID- 10906651
TI  - Pulsed-dye laser versus conventional therapy in the treatment of warts: a
      prospective randomized trial.
AB  - BACKGROUND: The clinical management of verrucae vulgaris is often challenging,
      and no ideal treatment currently exists. Early studies suggested that pulsed-dye
      laser (PDL) therapy might be highly effective in the treatment of verrucae,
      although more recent reports have been less optimistic. Previous studies have
      been retrospective or have consisted of a series of patients treated with PDL
      alone. OBJECTIVE: Our objective was to prospectively evaluate the efficacy of PDL
      therapy versus conventional therapy with liquid nitrogen cryotherapy or
      cantharidin in the treatment of warts. METHODS: Forty healthy adult patients with
      verrucae were randomized to receive either PDL (585 nm) therapy or conventional
      therapy. All enrollees also performed home therapy. Patients were eligible for up
      to 4 treatment sessions at 1-month intervals. Warts were individually counted and
      measured at the time of each treatment session. Complete response was defined as
      complete absence of verrucae with the presence of dermatoglyphics, and partial
      response was defined as a 50% or greater reduction in wart size. RESULTS: A total
      of 194 warts were evaluated by the conclusion of the study. Complete response was
      noted in an average of 70% of the warts treated with conventional therapy and in
      66% of those in the PDL group; this was statistically insignificant. Partial
      response was observed in an average of 82% of the warts in patients treated with
      conventional therapy and 87% in the PDL group. Verruca vulgaris responded more
      readily than verruca plantaris in both treatment groups. The mean number of
      treatments to achieve success was similar in both groups. CONCLUSION: The PDL is
      an efficacious form of therapy for verrucae, as is conventional therapy. PDL
      therapy should be considered among the better established approaches in the
      treatment of warts, although data from this trial suggest that this approach is
      probably not superior.

PMID- 10906652
TI  - Two considerations for patients with psoriasis and their clinicians: what defines
      mild, moderate, and severe psoriasis? What constitutes a clinically significant
      improvement when treating psoriasis?
AB  - The definitions of psoriasis severity and clinically significant improvement in
      psoriasis are used to classify treatments, obtain Food and Drug Administration
      approval, and determine product labeling and reimbursement. The Medical Advisory
      Board of the National Psoriasis Foundation has addressed these issues because of
      their importance in the clinical trials that are conducted to gain FDA approval
      of indications. Narrow indications, which are without a sound rational basis,
      will-in this era of constant oversight by third party payers-affect physicians'
      ability to manage patients with psoriasis. Body surface area (BSA) is usually
      used to define severity for clinical trials. It is not optimal for defining
      psoriasis severity because there are some patients with low BSA involvement who
      have very severe psoriasis and some patients with high BSA involvement who have
      mild psoriasis. We conclude that a quality of life (QOL) standard is better than
      BSA measurement for identifying patients with severe psoriasis. The second issue
      is what defines clinically significant improvement for patients with psoriasis.
      Setting an arbitrarily high criterion of clinical efficacy for new psoriasis
      treatments will likely limit the development and approval of useful treatments.
      To maximize the availability of useful psoriasis treatments, it is our thesis
      that psoriasis treatments should be approved when they have been shown to produce
      a statistically significant level of improvement in well-designed clinical
      trials.

PMID- 10906653
TI  - Topical anesthetics in dermatology.
AB  - Topical anesthetics are valuable tools for the dermatologists. The purpose of
      this study is to educate dermatologists about the pharmacology and clinical
      applications of topical anesthetics. A review of the current topical anesthetics
      was conducted. Several topical anesthetics are available to provide safe and
      effective cutaneous analgesia. Patient care can be improved by reducing the
      discomfort of local procedures and by minimizing the side effects of the
      anesthetics.

PMID- 10906654
TI  - Special skin symptoms seen in swimmers.
AB  - Inherent in the nature of every form of athletic endeavor are certain
      characteristics of the sport that can potentially produce pathologic changes in
      the various organ systems, including the skin. Swimming is no exception. We
      review some of the more common dermatologic conditions likely to be encountered
      by swimmers in the aqueous medium of their activity. Specific suggestions for
      practitioners who care for these athletes, encompassing treatment plans and
      preventive recommendations, are elucidated.

PMID- 10906655
TI  - Surgical pearl: forceps method for freezing benign lesion.

PMID- 10906656
TI  - Pigmented purpuric eruption associated with injection medroxyprogesterone
      acetate.
AB  - Pigmented purpuric eruptions are characterized clinically by purpura, most
      commonly petechial, and brownish pigmentation. Although there are several
      idiopathic variants, several drugs have been associated with these eruptions. We
      present a patient who experienced pigmented purpura on her lower extremities
      several months after initiating medroxyprogesterone acetate injection. The
      eruption cleared several weeks after discontinuation of the medication.

PMID- 10906657
TI  - Unilateral atrophic skin lesion with features of atrophoderma vermiculatum: a
      variant of the epidermal nevus syndrome?
AB  - We report a case of atrophic skin lesions similar to atrophoderma vermiculatum
      with unilateral distribution in a patient with an ipsilateral cataract, transient
      ipsilateral alopecia, and a seizure disorder. Atrophoderma vermiculatum may be a
      cutaneous marker for various internal abnormalities.

PMID- 10906659
TI  - All-trans-retinoic acid-induced scrotal ulcerations in a patient with acute
      promyelocytic leukemia.
AB  - Induction therapy with all-trans -retinoic acid has been shown to improve the
      outcome of patients with acute promyelocytic leukemia, although some side effects
      occur. Dry skin and lips are among the most common cutaneous side effects. We
      report a case of scrotal ulcerations induced by all-trans -retinoic acid in an
      American patient; to our knowledge this is the first such case reported.

PMID- 10906658
TI  - Pseudoxanthoma elasticum and calcinosis cutis.
AB  - A 42-year-old white woman presented with clinical and histologic manifestations
      of both calcinosis cutis and pseudoxanthoma elasticum: discrete milia-like
      calcifications at the anterior aspect of the neck, a funduscopic examination with
      classic eye findings, peripheral vascular disease, and a mottled appearance of
      the skin at the axillae, groin, and lateral aspects of the neck. A younger
      sibling had similar skin lesions and deteriorating visual acuity. The patient was
      normocalcemic and normophosphatemic. This case may represent the coincidental
      occurrence of two rare entities in the same person or may be suggestive of a
      pattern of dystrophic calcification associated with pseudoxanthoma elasticum.

PMID- 10906660
TI  - Dermatotherapy at the end of the century: an ex tempore perspective after looking
      into a forgotten herbal and into neglected recipes of folk medicine.

PMID- 10906661
TI  - Rejection overruled: a few more notes on submitting papers to The Blue Journal.

PMID- 10906662
TI  - Capillary leak syndrome in a patient treated with interleukin 2 fusion toxin for
      cutaneous T-cell lymphoma.

PMID- 10906663
TI  - Opiate-mediated pruritus and citation etiquette.

PMID- 10906666
TI  - Psoriasis remission time at the Dead Sea.

PMID- 10906668
TI  - Gentamicin release from hydroxyapatite/poly(ethyl methacrylate)/poly(methyl
      methacrylate)composites.
AB  - In this work the release kinetics of gentamicin sulfate (GEN) in samples composed
      by hydroxyapatite, poly(methyl methacrylate), and poly(ethyl methacrylate) has
      been studied. The release study was performed by soaking three samples in
      simulated body fluid at 37 degrees C; the medium was periodically replaced during
      70 days. The concentration of GEN was determined by the o-phtaldialdehyde method.
      The release profile shows three stages: the first stage, occurring during the
      first 10 h, corresponds to a fast release (nearly 30% of the drug is released in
      this period). The second stage is slower and includes from the first 10 h to 16
      days, releasing 60% of the total amount of GEN. The final stage is the slowest
      and it takes from 16 to 70 days (10% of GEN is released). The fraction of
      released GEN versus square root of time can be fitted to a third order
      polynomial, corresponding with the model proposed by Cobby et al. (J Pharm Sci
      1974;63:725-732). The characterization of the samples after the release study
      shows that a carbonate hydroxyapatite layer has grown on the whole surface of the
      composites.

PMID- 10906669
TI  - Amphiphilic poly(ether ester amide) multiblock copolymers as biodegradable
      matrices for the controlled release of proteins.
AB  - Amphiphilic poly(ether ester amide) (PEEA) multiblock copolymers were synthesized
      by polycondensation in the melt from hydrophilic poly(ethylene glycol) (PEG), 1,4
      dihydroxybutane and short bisester-bisamide blocks. These amide blocks were
      prepared by reaction of 1,4-diaminobutane with dimethyl adipate in the melt. A
      range of multiblock copolymers were prepared, with PEG contents varying from 23
      66 wt %. The intrinsic viscosity of the PEEA polymers varied from 0.58-0.78.
      Differential scanning calorimetry showed melting transitions for the PEG blocks
      and for the amide-ester blocks, suggesting a phase separated structure. Both the
      melting temperature and the crystallinity of the hard amide-ester segments
      decreased with increasing PEG content of the polymers. The equilibrium swelling
      ratio in phosphate buffered saline (PBS) increased with increasing amount of PEG
      in the polymers and varied from 1.7 to 3.7, whereas the polymer that contained 66
      wt % PEG was soluble in PBS. During incubation of PEEA films in PBS, weight loss
      and a continuous decrease in the resulting inherent polymer viscosity was
      observed. The rate of degradation increased with increasing PEG content. The
      composition of the remaining matrices did not change during degradation. A
      preliminary investigation of the protein release characteristics of these PEEA
      copolymers showed that release of the model protein lysozyme was proportional to
      the square root of time. The release rate was found to increase with increasing
      degree of swelling of the polymers.

PMID- 10906671
TI  - Prevention of fibrous layer formation between bone and adhesive bone cement: in
      vivo evaluation of bone impregnation with 4-META/MMA-TBB cement.
AB  - We have studied a new adhesive bone cement, that consists of 4
      methacryloyloxyethyl trimellitate anhydride (4-META) and methylmethacrylate (MMA)
      as monomers, tri-n-butyl borane (TBB) as the initiator, and
      polymethylmethacrylate powder (4-META/MMA-TBB cement). This cement has shown
      remarkable adhesive properties to bone in vitro. In this study, we assessed the
      interface in vivo periodically. The femora of rabbits were fenestrated and filled
      with either the 4-META/MMA-TBB cement or a conventional polymethylmethacrylate
      cement. The animals were killed after 1, 4, 12, and 24 weeks to analyze the
      interface by optical microscopy and transmission electron microscopy. Optical
      microscopic examinations showed that the cured 4-META/MMA-TBB adhesive cement
      bonded to bone directly for 24 weeks, whereas a fibrous tissue layer was observed
      between the bone and cured conventional cement at 12 weeks after the operation.
      The transmission electron microscopy views of 4-META/MMA-TBB cement bonded to
      bone demonstrated a unique "hybridized bone" with the cement in the subsurface of
      the substrate in every case. The formation of the hybridized bone indicates the
      bonding mechanism of the adhesive cement to bone, which prevents the fibrosis
      intervention between bone and cement. These results suggest that the
      biomechanical and adhesive properties of 4-META/MMA-TBB cement make it a useful
      bone-bonding agent in orthopedic surgery.

PMID- 10906670
TI  - Time course of transforming growth factor-beta(1) (TGF-beta(1)) mRNA expression
      in the host reaction to alginate-poly-L-lysine microcapsules following
      implantations into rat epididymal fat pads.
AB  - Microencapsulation of islets of Langerhans within semipermeable membranes has
      been proposed to prevent their immune destruction after transplantation. However,
      the successful application of this method is impaired by a pericapsular reaction,
      which eventually induces graft failure. Our goal is to study the role of
      cytokines in the pathogenesis of this reaction, using the model of alginate-poly
      L-lysine microcapsule implantation into Wistar rat epididymal fat pads (EFP). The
      specific objective of this study was to determine the time course of transforming
      growth factor (TGF)-beta(1) mRNA expression by semi-quantitative reverse
      transcriptase-polymerase chain reaction. Microcapsules induced an increase of TGF
      beta(1) mRNA expression that reached a maximum 14 days after implantation. Seven,
      14, 30, and 60 days after microcapsule implantation, the expression of TGF
      beta(1) mRNA was significantly higher in pericapsular infiltrate cells than in
      nonimplanted EFP cells (p<0.05, p<0.0001, p<0.005, and p<0.01, respectively).
      Injection of physiological saline induced a small and gradual augmentation of TGF
      beta(1) mRNA expression with a maximum 30 days after injection (p<0.01 vs.
      nonimplanted EFP cells). These results demonstrated that microcapsule
      implantation, in comparison with saline injection, induce an early, extended, and
      amplified TGF-beta(1) mRNA expression. This suggests that TGF-beta(1) plays a
      role in the pathogenesis of the pericapsular host reaction.

PMID- 10906672
TI  - Influence of preparation conditions on the microstructure and bioactivity of
      alpha-CaSiO(3) ceramics: formation of hydroxyapatite in simulated body fluid.
AB  - Two different reagents, NaOH and NH(4)OH, were used to precipitate CaSiO(3)
      precursor powders from ethanol solutions of Ca(NO(3))(2). 4H(2)O and
      Si(OC(2)H(5))(4). The resultant powders of different Ca/Si ratio and residual
      Na(2)O content exhibited significant differences in the microtexture of the
      resulting sintered alpha-CaSiO(3) ceramics. The microtexture of the ceramics from
      the NaOH system (CS-Na) contained smaller grain sizes and a thicker glassy phase
      at the grain boundaries than those produced using NH(4)OH (CS-NH). The CS-Na
      ceramics were soaked in a simulated body fluid (SBF) at 36.5 degrees C for 2 h
      and 1, 5, 6, 10, 21, and 30 days while the CS-NH ceramics were soaked for 1, 5,
      7, 15, 20, and 25 days using the same conditions. Hydroxyapatite (HAp) formed on
      the surfaces of both samples but at different formation rates due to differences
      in the microstructure. The CS-Na ceramics showed faster HAp formation because
      their smaller alpha-CaSiO(3) grains dissolved more readily, allowing the calcium
      concentration in the SBF quickly to approach the appropriate condition for
      nucleation of HAp. In addition, the thicker glassy phase at the grain boundaries
      facilitated a faster formation of silanol on the surface of the amorphous SiO(2)
      interlayer, a reaction that is considered to be a prerequisite for HAp formation.
      The formation of the HAp layer on the CS-Na ceramics therefore was very fast (12
      microm/day), and their surfaces were covered completely within 5 days. A layer
      thickness of about 110 microm was achieved in 30 days, in contrast with the CS-NH
      ceramics, which took about 25 days to be fully covered with a 60-microm layer of
      HAp.

PMID- 10906673
TI  - Rheologic and NMR characterization of monoglyceride-based formulations.
AB  - This paper describes the production and characterization of semi-solid
      formulations based on monoglycerides from canola oil and water as drug-delivery
      systems. In order to obtain new formulations with different characteristics in
      terms of viscosity, bioadhesiveness, and solubilization capacity, a third
      component was added to the monoglyceride-water system. Nine excipients were
      tested, namely soy oil, isopropylmyristate, isopropylpalmitate, tripalmitin,
      tristearin, glyceryl monostearate, glycerol, propylene glycol, and ethanol. In
      particular, the effect of each excipient on the viscosity and stability of the
      formulation was investigated. It was found that ethanol dramatically influenced
      the viscosity of the monoglyceride-water system, resulting in the formation of
      stable forms. In addition, ethanol suitably could be used for the solubilization
      of water-insoluble lipophilic drugs. This promising ternary system was
      characterized by microscopic, NMR spectroscopic, and rheologic techniques. (1)H
      and (13)C NMR studies were made of Myverol to verify the molecular structure and
      isomer distributions of this commercial monoacylglycerol mixture. The
      microstructure of an isotropic solution consisting of Myverol [1.8% (w/w)],
      ethanol (42.9%), and water (55.3%) was studied by the multi-component self
      diffusion NMR method. From the self-diffusion coefficient (D) of the
      monoglycerides (8.8 x 10-11 m(2)/s), an "apparent spherical hydrodynamic radius"
      of ca. 2.48 nm was calculated for the micellar aggregate. A nearly spherical
      shape is consistent with these values since the extended hydrocarbon chain of the
      longest monoglyceride (17 carbons) is ca. 2.2 nm long. The D's of water and
      ethanol reveal they do not associate (no attractive nonbonding interactions)
      appreciably with the fatty acid micelles.

PMID- 10906674
TI  - Distribution and serum concentration of sisomicin released from fibrin glue
      sealed dacron graft in the rat and human.
AB  - We investigated whether or not fibrin glue (FG) used as a sealant in vascular
      prostheses to prevent leakage might be useful as a carrier of antibiotics for the
      prevention of local graft infection. Sisomicin (SISO) was incorporated into
      fibrin glue (SISO-FG) and evaluated as to its safety and pharmacokinetics. SISO
      (1.75 mg) -FG Dacron grafts were implanted subcutaneously in the anterior
      abdominal region of Sprague-Dawley rats, and then the changes in SISO
      concentrations in the serum and in the tissue around the implantation sites were
      compared with those same sites in rats that had had intravenous injection of SISO
      (1.75 mg). The serum SISO concentrations were significantly lower in the SISO-FG
      Dacron graft group than they were in the intravenous injection group. However,
      until 4 h after implantation the SISO concentrations in the tissues around the
      implantation sites were significantly higher in the SISO-FG Dacron group than
      they were in the iv injection group, and the peak concentrations during that time
      were 5.8 times higher for the SISO-FG Dacron group than they were for the
      intravenous injection group. The ratio of the area under the tissue concentration
      time curve of SISO (AUC tissue) after implantation of the SISO-FG Dacron graft to
      that after intravenous injection of SISO was 13.08. Therefore, FG was considered
      to control the release of SISO into the serum and to maintain a high SISO
      concentration in the tissue around the implantation site. Clinically, SISO (45
      mg) -FG was applied directly to the Dacron grafts implanted in 10 patients who
      underwent prosthetic vascular reconstruction. No graft infection was observed in
      any of the patients who received SISO-FG Dacron grafts. The mean serum
      concentration of SISO was 0.65+/-0.17 microg/mL after 1 h and 0.33+/- 0.21
      microg/mL after 3 h. The results of these clinical applications are in close
      correlation with those of the animal experiment and suggest that FG is useful as
      a carrier of SISO, allowing its controlled release for the prevention of local
      infection.

PMID- 10906676
TI  - New bioactive, degradable composite microspheres as tissue engineering
      substrates.
AB  - Novel bioactive, degradable polymer/glass/ceramic composite microspheres were
      developed using a solid-in-oil-in-water (s/o/w) emulsion solvent removal method.
      Modified bioactive glass (MBG) powders were encapsulated into the polylactic acid
      (PLA) matrix. Scanning electron microscopy and energy-dispersive X-ray analyses
      revealed that the MBG powders were mostly embedded in the polymer matrix, and
      submicron-size pores were present at the surface. Immersion in simulated
      physiological fluid (SPF) was used to evaluate the surface reactivity of the
      microspheres. The polymeric surface was fully transformed into carbonated calcium
      hydroxyapatite (c-HA) after 3 weeks of immersion. In contrast, PLA microspheres
      showed no evidence of any calcium phosphate deposition. Ion concentration
      analyses revealed a decrease in Ca and P concentrations and an increase in Si
      concentration in the SPF immersed with composite microspheres during the 3-week
      period. The Ca and P uptake rates decreased after 2 days of incubation. This
      coincided with the decrease of the Si release rate. These data lend support to
      the suggestion that the Si released from the MBG powders present in the polymer
      matrix is involved in the formation of the Ca-P layer. Our results support the
      concept that these new bioactive, degradable composite microspheres may serve as
      microcarriers for synthesis of bone and other tissues in vitro and in vivo.

PMID- 10906675
TI  - In vitro evaluation of the genotoxicity of a naturally occurring crosslinking
      agent (genipin) for biologic tissue fixation.
AB  - The objective of the present study was to evaluate in vitro, using Chinese
      hamster ovary (CHO-K1) cells, the genotoxicity of genipin, a naturally occurring
      crosslinking agent. Glutaraldehyde, the most commonly used crosslinking agent for
      biologic tissue fixation, was employed as a reference chemical. The selected
      procedures for this evaluation were the micronucleus (MN) and sister chromatid
      exchange (SCE) assays with or without the addition of a metabolic activation
      system (S9 mix). Before starting the genotoxicity assays, the maximum
      noncytotoxic amounts of glutaraldehyde and genipin were determined using the MTT
      assay. The results obtained in the MTT assay revealed that the cytotoxicity of
      genipin was significantly lower than that of glutaraldehyde with or without S9
      mix. The frequencies of MN observed in the cases drugged with varying
      concentrations of glutaraldehyde or genipin were not statistically different from
      those seen in the negative controls (blank) in the presence or absence of S9 mix.
      However, it was noted that glutaraldehyde significantly inhibited the cell-cycle
      progression while the cells drugged with genipin did not result in cell-cycle
      delay. In the SCE assay, the numbers of SCE per cell observed in the cases
      drugged with varying concentrations of glutaraldehyde were significantly greater
      than those found in the negative controls with or without S9 mix. Nevertheless,
      these numbers were still low compared to the numbers of SCE induced by the strong
      mutagens used as our positive control substances. This suggests that
      glutaraldehyde may produce a weakly clastogenic response in CHO-K1 cells. In
      contrast, the numbers of SCE per cell obtained in the cases drugged with genipin
      were comparable to those observed in the negative controls in those that were
      except drugged with the highest dose (50 ppm). This suggests that genipin does
      not cause clastogenic response in CHO-K1 cells provided its concentration is
      lower than 50 ppm. In conclusion, as far as cytotoxicity and genotoxicity are
      concerned, genipin is a promising crosslinking agent for biologic tissue
      fixation.

PMID- 10906677
TI  - Fixation of biological tissues with a naturally occurring crosslinking agent:
      fixation rate and effects of pH, temperature, and initial fixative concentration.
AB  - In an attempt to overcome the cytotoxicity problem of the glutaraldehyde-fixed
      tissues, a naturally occurring crosslinking agent (genipin) was used by our group
      to fix biological tissues. The study was intended to investigate the rate of
      tissue fixation by genipin. Glutaraldehyde was used as a control. In addition,
      the degrees of tissue fixation by genipin at different pHs (pH 4.0, pH 7. 4, pH
      8.5, or pH 10.5), temperatures (4 degrees C, 25 degrees C, 37 degrees C, or 45
      degrees C), and initial fixative concentrations (0.250%, 0.625%, or 1.000%) were
      examined. The results obtained revealed that the rate of tissue fixation by
      glutaraldehyde was significantly faster than that by genipin. The degree of
      tissue fixation by genipin may be controlled by adjusting its fixation duration
      or fixation conditions. The order in degree of tissue fixation by genipin at
      different pHs, from high to low, was: at nearly neutral pH (pH 7.4 or pH 8.5) >
      at basic pH (pH 10.5) > at acidic pH (pH 4.0). The degrees of tissue fixation by
      genipin at different temperatures were about the same, except for that at 4
      degrees C. In contrast, the initial fixative concentration did not seem to affect
      the degree of tissue fixation by genipin, if only the amount of genipin in the
      fixation solution was sufficient to complete tissue fixation. The concentrations
      of genipin in the aqueous solutions at different pHs, temperatures, and initial
      fixative concentrations tended to decrease with time with or without the
      occurrence of tissue fixation. This indicated that genipin was not stable in the
      aqueous solution. The instability of aqueous genipin was more remarkable with
      increasing pH or temperature. The results obtained in this study may be used to
      optimize the fixation process for developing bioprostheses fixed by genipin.

PMID- 10906678
TI  - Well-defined sulfobetaine-based statistical copolymers as potential
      antibioadherent coatings.
AB  - The potential use of novel poly(sulfobetaine) copolymers as antibioadherent
      coatings was investigated using Pseudomonas aeruginosa as a model microorganism
      and human macrophages and 3T3 mouse embryonic fibroblasts. Two well-defined
      statistical copolymers with narrow molecular weight distributions were prepared
      by group transfer copolymerization of n-butyl methacrylate (nBuMA) with either 10
      or 30 mol % 2-(dimethylamino)ethyl methacrylate (DMAEMA). Sulfobetainized nBuMA
      DMAEMA copolymers (poly[sulfobetaine-stat-nBuMA]) were obtained by treating these
      precursor polymers with 1,3-propanesultone under mild conditions. Both proton NMR
      spectroscopy and elemental microanalyses indicated that essentially all the
      DMAEMA residues were derivatized in both copolymers. Poly(methyl methacrylate)
      (PMMA) discs were coated with the sulfobetainized nBuMA-DMAEMA copolymers and the
      bioadherent properties of these coated materials were compared with those of
      PMMA. Statistically significantly fewer (p<.05) bacteria, macrophages, and
      fibroblasts adhered to the poly(sulfobetaine-stat-nBuMA)-coated PMMA than to the
      uncoated PMMA. The poly(sulfobetaine-stat-nBuMA) copolymer containing the higher
      proportion (30 mol %) sulfobetainized DMAEMA residues proved to be the more
      effective antibioadherent coating. The antibioadherent properties of these
      coating materials may allow the cost-effective production of dirt-resistant, easy
      to clean work surfaces, bioinert coatings for medical devices, and antifouling
      coatings for marine, agricultural, and industrial applications.

PMID- 10906679
TI  - Conversion of octacalcium phosphate in calcium phosphate cements.
AB  - This study investigated the in vitro conversion reaction in calcium phosphate
      cements (CPCs) containing octacalcium phosphate (OCP) as one of the reagents. OCP
      is known to be a precursor for apatite formation in vivo. The reaction products
      were characterized using infrared spectroscopy and X-ray diffraction. Although
      the conversion of OCP into hydroxyapatite is thermodynamically favorable, OCP
      only yields apatite formation in CPC provided it is combined with a highly
      soluble Ca(2+) and OH(-) releasing reaction partner. In this respect,
      tetracalcium phosphate is a promising compound. Adding small amounts of
      monocalcium phosphate monohydrate can stimulate the setting through intermediate
      brushite formation. The preparation method of OCP might drastically affect the
      performance of the cement. The reaction path of the setting of these CPC probably
      does not conform to the singular point principle described in the literature, and
      an in situ hydrolysis of OCP to apatite is conceivable. Simulation of apatite
      formation using OCP as the precursor and/or seed in CPC might be beneficial for
      some biomedical applications.

PMID- 10906681
TI  - High-resolution transmission electron microscopy investigations of a highly
      adhesive hydroxyapatite coating/titanium interface fabricated by ion-beam
      assisted deposition.
AB  - An atomic intermixing layer, 25 nm in width, has been identified by high
      resolution transmission electron microscopy (HRTEM) and energy-dispersive X-ray
      spectroscopy (EDS) analysis at the ceramic/metal interface of a hydroxyapatite
      (HA) coating/titanium implant prepared by an ion-beam-assisted deposition (IBAD)
      technique and post-heat-treatment process. The detailed interfacial
      microstructure revealed a gradient evolution of both the structure and
      composition of the interfacial phases from the titanium substrate to HA coatings.
      An enhancement of the tensile bond strength was found and was attributed to the
      possible chemical bonding at the ceramic/metal interface.

PMID- 10906680
TI  - Reinforcement of a self-setting calcium phosphate cement with different fibers.
AB  - A water-based calcium phosphate cement (CPC) has been used in a number of medical
      and dental procedures due to its excellent osteoconductivity and bone replacement
      capability. However, the low tensile strength of CPC prohibits its use in many
      unsupported defects and stress-bearing locations. Little investigation has been
      carried out on the fiber reinforcement of CPC. The aims of the present study,
      therefore, were to examine whether fibers would strengthen CPC, and to
      investigate the effects of fiber type, fiber length, and volume fraction. Four
      different fibers were used: aramid, carbon, E-glass, and polyglactin. Fiber
      length ranged from 3-200 mm, and fiber volume fraction ranged from 1.9-9.5%. The
      fibers were mixed with CPC paste and placed into molds of 3 x 4 x 25 mm. A
      flexural test was used to fracture the set specimens and to measure the ultimate
      strength, work-of-fracture, and elastic modulus. Scanning electron microscopy was
      used to examine specimen fracture surfaces. Fiber type had significant effects on
      composite properties. The composite ultimate strength in MPa (mean +/- SD; n = 6)
      was (62+/-16) for aramid, (59+/-11) for carbon, (29+/-8) for E-glass, and (24+/
      4) for polyglactin, with 5.7% volume fraction and 75 mm fiber length. In
      comparison, the strength of unreinforced CPC was (13+/-3). Fiber length also
      played an important role. For composites containing 5.7% aramid fibers, the
      ultimate strength was (24+/-3) for 3 mm fibers, (36+/-13) for 8 mm fibers, (48 +/
      14) for 25 mm fibers, and (62+/-16) for 75 mm fibers. At 25 mm fiber length, the
      ultimate strength of CPC composite was found to be linearly proportional to fiber
      strength. In conclusion, a self-setting calcium phosphate cement was
      substantially strengthened via fiber reinforcement. Fiber length, fiber volume
      fraction, and fiber strength were found to be key microstructural parameters that
      controlled the mechanical properties of CPC composites.

PMID- 10906682
TI  - Development of "heparin-like" polymers using swift heavy ion and gamma radiation.
      I. Preparation and characterization of the materials.
AB  - The development of ideal antithrombogenic polymers, a major problem in
      biomaterials sciences, is a primary objective in the fields of cardiovascular
      prostheses, artificial hearts, and other devices. To decrease their
      thrombogenicity, which remains the major obstacle, we have developed polymeric
      materials endowed with a specific affinity for antithrombin III (ATIII) and thus
      able, like heparin, to catalyze the inhibition of thrombin by ATIII. Sulfonate
      and sulfonamide groups are introduced onto phenyl rings belonging to styrene
      residues, which are radiation grafted (using swift heavy ion and gamma radiation)
      onto poly(vinylidene difluoride) (PVDF) and also onto poly(vinylidene
      fluoride/hexafluoropropylene) [P(VDF-HFP)]. In contrast to gamma radiation, which
      leads to a homogeneous modification, the advantage of swift heavy ion grafting is
      that only small regions are modified; thus, the surface may present hydrophilic
      (corresponding to the modified areas) and hydrophobic microdomains (corresponding
      to the unmodified areas) of different sizes, depending on the absorbed dose and
      grafting yield. Surface topography and composition are characterized by scanning
      electron microscopy (SEM) and atomic force microscopy (AFM). Sulfur, sodium,
      fluorine, and carbon are determined by scanning electron microscopy combined with
      energy-dispersive X-ray analysis (SEM-EDXA). The amount of fluorine decreases as
      polystyrene (PS) is grafted, whatever the kind of radiation and polymer. When the
      polymers are functionalized, the amount of fluorine also decreases while sodium
      and sulfur appear. Functionalization seems to increase the roughness of the
      surface, and its area.

PMID- 10906683
TI  - In vivo evaluation of the bond strength of adhesive 4-META/MMA-TBB bone cement
      under weight-bearing conditions.
AB  - In order to minimize the problems associated with implant fixation using acrylic
      bone cement, we studied a new adhesive bone cement that consists of 4
      methacryloyloxyethyl trimellitate anhydryde (4-META) and methylmethacrylate (MMA)
      as monomers, tri-n-butylborane (TBB) as an initiator, and PMMA powder (4-META/MMA
      TBB cement). It shows remarkable adhesive properties to metal and bone in vitro.
      The purpose of this study was to evaluate the strength of the bond of the cement
      to both metal and bone in vivo under weight-bearing conditions. Metal prostheses
      were implanted in the right femora of 12 rabbits using either adhesive 4-META/MMA
      TBB cement or the conventional PMMA cement, as the control, for fixation. After 4
      and 12 weeks, both femora were excised and the same operations were performed in
      the left femora in vitro. Eighteen femora were sectioned for the mechanical
      assessment of the bone-cement and cement-implant interfaces. 4-META/MMA-TBB
      cement had a significantly higher interfacial shear strength than the
      conventional PMMA cement: 201 N and 90 N, on average, for the implant-cement
      interface (p<0.01); and 138 N and 89 N, on average, for the bone-cement interface
      (p<0.01), at 12 weeks. The present results suggest the efficacy of 4-META/MMA-TBB
      cement in providing greater fixation of implants to bone and promise a firmer
      intramedullary fixation than the control conventional PMMA cement.

PMID- 10906684
TI  - The influence of impaired wound healing on the tissue reaction to percutaneous
      devices using titanium fiber mesh anchorage.
AB  - The objective of this investigation was to study the influence of impaired wound
      healing on the soft-tissue response to percutaneous devices using titanium fiber
      mesh anchorage. For this reason, diabetes mellitus was induced in rabbits with
      alloxan. Untreated rabbits were used as controls. Two implant types were inserted
      subcutaneously: two-stage percutaneous devices as well as separate titanium fiber
      mesh sheets. The soft-tissue response to both implants was assessed by clinical,
      histologic, and histomorphometric evaluation. Clinically, we observed a higher
      number of infectious complications around percutaneous implants in diabetic
      animals. Histologic and histomorphometric analyses revealed that severe diabetes
      effected matrix maturation and delayed neovascularization (p<0.05). We also
      observed higher numbers of inflammatory cells in the mesh porosity of
      percutaneous implants in severely diabetic animals (p = 0.09). Our results
      indicate that severe, uncontrolled diabetes negatively influences the maturity
      and neovascularization of connective tissue inside the fiber mesh porosity. The
      higher number of infectious complications in diabetic animals suggests that the
      presence of impaired healing conditions facilitates infection around skin
      penetrating devices.

PMID- 10906685
TI  - Alveolar mononuclear cells can develop into multinucleated osteoclasts: an in
      vitro cell culture model.
AB  - Previous studies have shown that osteoclasts are derived from mononuclear cells
      of hemopoietic bone marrow and peripheral blood. The purpose of this study was to
      demonstrate the presence of multinucleated osteoclasts after adding alveolar
      mononuclear cells to new-born rat calvaria osteoblasts in vitro. To utilize
      osteoclast-free bone, fetal calvariae were obtained from newborn Wistar-rats and
      cultured in DMEM medium for 14 days. On the day of osteoblast culture, alveolar
      mononuclear cells were isolated from newborn Wistar rats with a serial washing
      method and then co-cultured with the calvarial osteoblasts. Bone resorption
      characteristics were observed both with light and scanning electron microscopy.
      When alveolar mononuclear cells were cultured for 14 days on the calvarial
      osteoblasts in response to 1 alpha, 25-dihydroxyvitamin D3, they formed tartrate
      resistant acid phosphatase (TRAP)-positive mononuclear and multinucleated cells.
      Resorption pits were seen in the 7-14 days long-term cultures. These results
      indicate that osteoclasts can be derived from alveolar mononuclear cells in vitro
      when a suitable microenvironment is provided by calvarial osteoblasts and vitamin
      D(3).

PMID- 10906686
TI  - Attenuation of acoustic emission body waves in acrylic bone cement and synthetic
      bone using wavelet time-scale analysis.
AB  - This article addresses acoustic emission (AE) wave attenuation in acrylic bone
      cement and wave attenuation due to the existence of material interface between
      acrylic bone cement and sawbone. In this article, a series of tests were
      performed using standard pencil lead break sources. The attenuation features
      inside acrylic bone cement and sawbone materials and the attenuation due to the
      existence of material interfaces such as cement-cement and cement-sawbone were
      studied. In addition, the discrete wavelet-based signal energy decomposition
      method was introduced to examine detail breakdown of signal energy distribution
      of attenuation. From the tests, it was observed that the attenuation of AE signal
      was linear with respect to the wave travel distance for both energy and
      amplitude. Furthermore, AE energy attenuation was more sensitive than AE
      amplitude attenuation. In the analysis of attenuation due to material interfaces,
      the couplant plays a major role in reducing the attenuation at the interfaces.
      The attenuation at an interface composed by different material is less compared
      with an interface composed by the same material.

PMID- 10906687
TI  - Characterization of peroxide ions in hydroxyapatite lattice.
AB  - The incorporation of peroxide ions was confirmed in the heat treatment of
      hydroxyapatite (HA) powder under air as well as under oxygen atmosphere, by using
      X-ray diffraction, Raman, and infrared spectroscopy. Peroxide ions associated
      with vacancies were sited in the channel of HA lattice along the c-axis through
      the substitution of a portion of OH radicals. The molecular ions constituted a
      symmetric vibrator with a stretching vibration active in Raman spectrometry. This
      vibration was recorded at 750 cm(-1) in the Raman spectra of O(2)(2-)-containing
      HA samples. The final product was a solid solution of hydroxyl- and peroxide
      apatite. However, the existence of peroxide ions in the HA lattice caused the
      contraction of the unit-cell dimensions of HA materials. In addition, a new
      hydrogen bond was formed between peroxide ions and adjacent OH radicals by using
      molecular spectroscopy analysis. During annealing treatment in air, peroxide ions
      decomposed and the substituted OH radicals re-enter the HA lattice, resulting in
      the elimination of the structural aberrations caused by the incorporation of
      peroxide ions. Concentration of the peroxide ions included in HA samples was
      measured by chemical analysis.

PMID- 10906688
TI  - A novel injectable bioactive bone cement for spinal surgery: a developmental and
      preclinical study.
AB  - The injection of bone cement by minimally invasive techniques for the treatment
      of vertebral body fractures or for stabilization of an osteoporotic vertebral
      body is regarded as promising in spinal surgery. The purpose of this study was to
      develop a novel injectable bioactive bone cement to address such concerns. The
      cement was composed mainly of strontium-containing hydroxyapatite (Sr-HA) filler
      and Bisphenol A Diglycidylether Dimethacrylate (D-GMA) resin. The Sr-HA filler
      was prepared by precipitation and calcination, then analyzed with Fourier
      transform infrared (FTIR) spectra and X-ray diffraction (XRD) patterns. Samples
      of strontium-containing hydroxyapatite cement (SrHAC) were formed by a
      combination of powder filler and resin matrix, with the setting time and peak
      temperature recorded. Cell relative growth rate (RGR), Tetrazolium bromide (MTT),
      and haemolysis tests were used to detect initial in vitro biocompatibility of the
      new cement. In vitro spinal biomechanical testing and morphological observation
      after bone cement injection were performed on pig spines. Results indicate that
      the setting time and peak temperature of the cement was 15 min and 55 degrees C,
      respectively. Cytotoxicity of the cement was class 1 (no cytotoxicity) and
      haemolysis was 1% (no haemolysis). Stiffness after cement injection and fatigue
      loading were 112% and 95% of the intact bone, respectively, which is similar to
      that of natural bone. Radiopacity of SrHAC allowed easy radiographic imaging. The
      use of SrHAC cement is, thus, promising in spinal surgery.

PMID- 10906689
TI  - Improvement of bioactivity of H(2)O(2)/TaCl(5)-treated titanium after subsequent
      heat treatments.
AB  - Commercially pure titanium was treated with a H(2) O(2)/3mM TaCl(5) solution at
      80 degrees C for various periods and a titania gel layer was formed on the
      surface. This gel remained amorphous when heating for 1 h below 200 degrees C and
      transformed to anatase after heating between 300 degrees and 600 degrees C. The
      anatase titania gel layers were found to be bioactive as to deposit carbonate ion
      incorporated apatite within 1 day of immersion in the Kokubo solution, whereas
      the amorphous layers did not deposit apatite within 7 days. The apatite particles
      were found to nucleate preferentially inside the cracks prevailing in the thicker
      gel layers of 1-h chemically treated specimens. After immersing for 2 days, the
      titanium specimens were almost completely covered by apatite. Elimination of
      peroxide radicals from the titania gel and formation of anatase upon subsequent
      heating are considered to be responsible for the enhanced ability of apatite
      deposition.

PMID- 10906690
TI  - Isolation and characterization of osteoblast cultures from normal and osteopenic
      sheep for biomaterials evaluation.
AB  - Being very useful in the analysis of bone cell differentiation and activity,
      osteoblast cultures are also used in the in vitro biocompatibility study of new
      materials. The aim of this work was to evaluate sheep osteoblast cultures derived
      from normal and ovariectomized animals, and then to assess the in vitro
      biomaterial behavior on these cultures, taking into account the quality of bone
      where orthopedic devices are clinically used. For this purpose, we characterized
      sheep osteoblast cultures, isolated from iliac crest bone of normal (NB
      osteoblast culture) and osteopenic after ovariectomy (OB osteoblast culture)
      sheep. Moreover, we studied cell behavior when cultured on different biomaterials
      (titanium and two biological glasses, RKKP and AP40). Cell characterization at
      baseline demonstrated that both cultures (NB and OB) showed normal osteoblastic
      behavior. On the contrary, osteoblasts derived from osteopenic bone and
      cultivated on AP40 for 6 days revealed a different behavior in terms of both cell
      morphology and metabolic activity. Statistical analysis (one-way analysis of
      variance and Scheffe's post hoc multiple-comparison tests) revealed significant
      differences in Ca level (p<0.0005), MTT test (p<0.0005) and OC production
      (p<0.05). These in vitro tests demonstrated that sheep osteoblast cultures can be
      useful when determining biocompatibility and osteointegration of orthopedic
      materials, and also when evaluating for the presence of osteoporosis.

PMID- 10906691
TI  - Histologic evaluation of the inflammatory response around implanted hollow fiber
      membranes.
AB  - Hollow fiber membranes are enjoying widespread use as barrier materials in many
      implanted applications. In order to predict in vivo device behavior, it is
      important to understand and quantify the changes to the membrane and to the
      tissue immediately surrounding it that occur following implantation. We have
      considered a range of commercially available hollow fiber membranes for their
      suitability as candidates for subcutaneously implanted applications. Through
      analysis of excised tissue sections by light microscopy, membranes were screened
      at 3, 6, and 12 weeks post-implantation for the ability to maintain integrity,
      foreign-body reaction, and thickness of the external fibrotic capsule layer. The
      polysulfone microfiltration membranes and cellulose diacetate membranes
      investigated were found to be unsuitable owing to extensive degradation. All
      membranes exhibited typical foreign body reaction with fibrotic capsule
      formation. The thinnest capsules were observed on the regenerated cellulose
      microdialysis membranes and the polysulfone ultrafiltration membranes. Extensive
      cellular penetration into the membrane matrix of the latter was observed, but did
      not appear to affect the foreign body reaction. A heat-sealing method was also
      considered for thermoplastic membranes and found to effectively prevent cellular
      penetration into the lumen of the hollow fiber for the duration of the 12-week
      implantation.

PMID- 10906692
TI  - New biocompatible polymer surface coating for stents results in a low neointimal
      response.
AB  - Clinical studies indicate a more pronounced endothelial response after stent
      implantation than after balloon inflation. This might be related to the metal
      surface of the stent, and therefore it is speculated that coating of the stent
      might partially prevent hyperplasia. One coated and one noncoated Palmaz-Schatz
      stent were implanted in two separate coronary arteries of seven pigs. The coating
      was composed of methylmethacrylate (MMA) (hydrophobic, 70 mol %) and 2
      hydroxyethyl methacrylate (HEMA) (hydrophilic 30 mol %). After sacrifice (3
      weeks), cross sections were made of the stented areas. Vessel wall reaction was
      calculated both independently and dependently of local vessel wall injury due to
      the stent struts. Overall, vessel wall reaction of the coated stents was lower
      than that of the noncoated stents. The degree of hyperplasia was linearly related
      to the degree of stent-induced vessel wall injury. Analyses of all the struts
      showed that significantly less hyperplasia occurred in the coated versus
      noncoated stents. In this porcine coronary artery model, the MMA/HEMA stent
      coating resulted in significantly reduced vessel wall response. However, it
      remains to be determined whether this favorable outcome will also be present in
      humans.

PMID- 10906693
TI  - Cell-cycle control in cell-biomaterial interactions: expression of p53 and Ki67
      in human umbilical vein endothelial cells in direct contact and extract testing
      of biomaterials.
AB  - Current biocompatibility testing involves the demonstration of cell
      proliferation, which is usually interpreted as a sign of positive
      biocompatibility when the materials sustain cell proliferation. As the field of
      biomaterials research is rapidly moving toward tissue-engineered devices and
      hybrid organs, control of cell function has become a main topic. Cell function,
      which involves specific differentiation pathways, cannot be separated from cell
      cycle control. The study of cell-cycle control is an important extension of
      routine proliferation assays and has extensive roots in developmental and tumor
      biology. We studied the expression of the tumour suppressor gene p53 and the
      proliferation-associated antigen Ki67 of endothelial cells in response to
      biomaterial contact. Cells were seeded in six- or 24-well plates, in which one or
      three 12-mm-diameter biomaterial disks were laid down. After 48- and 72-h
      incubation periods, cells were processed for flow cytometry, immunofluorescence,
      or Western blotting. The following materials were used: titanium, NiCr alloy, and
      CoCr alloy. Cells were also exposed to 24-h (ISO-norm) extracts in 25-cm(2)
      culture flasks (600, 000 cells) for 24 and 48 h. For extract testing, serially
      diluted Ni-ion suspensions were also used. Human umbilical vein endothelial cells
      adhered to metal surfaces and started forming a monolayer within 3 days. Ki67
      expression was positive in more than 60% after 2 days and decreased markedly
      after 3 days of adhesion. During this time cells developed focal contacts and
      produced a fibronectin matrix. p53 expression could be demonstrated with Western
      blotting and flow cytometry, but not with immunofluorescence. Differences due to
      both culturing time and material were found in expression patterns with both
      methods. Inverse correlations between Ki67 and p53 expression were detected,
      which are probably based on culture kinetics. The results indicate that
      expression of p53 and also Ki67 is clearly influenced by biomaterials in direct
      contact testing, despite the absence of obvious morphological differences. The
      p53 marker can be used for defining cell function in more detail, although the
      correlation with specific physiological function has still to be clarified.

PMID- 10906694
TI  - A theoretical and experimental analysis of polymerization shrinkage of bone
      cement: A potential major source of porosity.
AB  - A theoretical basis for understanding polymerization shrinkage of bone cement is
      presented based on density changes in converting monomer to polymer. Also, an
      experimental method, based on dilatometry and the Archimedes' principle is
      presented for highly precise and accurate measurement of unconstrained volumetric
      shrinkage of bone cement. Furthermore, a theoretical and experimental analysis of
      polymerization shrinkage in a constrained deformational state is presented to
      demonstrate that porosity can develop due to shrinkage. Six bone-cement
      conditions (Simplex-Ptrade mark vacuum and hand mixed, Endurancetrade mark vacuum
      mixed, and three two-solution experimental bone cements with higher initial
      monomer levels) were tested for volumetric shrinkage. It was found that shrinkage
      varied statistically (p< or = 0.05) from 5.1% (hand-mixed Simplex-Ptrade mark) to
      6.7% (vacuum-mixed Simplex-Ptrade mark) to 10.5% for a 0.6:1 (polymer g/monomer
      mL) two-solution bone cement. Shrinkage was highly correlated with initial
      monomer content (R(2) = 0.912) but with a lower than theoretically expected rate.
      This discrepancy was due to the presence of residual monomer after
      polymerization. Using previously determined residual monomer levels, the
      theoretic shrinkage analysis was shown to be predictive of the shrinkage results
      with some residual monomer left after polymerization. Polymerization of a two
      solution bone cement in a constrained state resulted in pores developing with
      volumes predicted by the theory that they are the result of shrinkage. The
      results of this study show that shrinkage of bone cement under certain
      constrained conditions may result in the development of porosity at the implant
      bone cement interface and elsewhere in the polymerizing cement mantle.

PMID- 10906695
TI  - Modulating the biocompatibility of polymer surfaces with poly(ethylene glycol):
      effect of fibronectin.
AB  - A novel approach described earlier for improving polymer substratum
      biocompatibility(1) is further elucidated. Polysulfone (PSf) spin-coating films
      were modified by covalent end-on grafting of hydrophilic and sterically demanding
      photo-reactive poly(ethylene glycol) (PEG) conjugates (ABMPEG; 10 kDa). The
      degree of grafting density was varied systematically, yielding a wide spectrum of
      attained surface characteristics monitored by air-water contact angles (captive
      bubble method). Fibronectin (FN) adsorption was studied by in situ ellipsometry
      and found to decrease monotonically as ABMPEG grafting density increased. The
      adhesive interaction of human skin fibroblasts with these substrata and, in
      particular, the effect of FN precoating were investigated in detail. A clear
      optimum of cell-substratum interactions was found for mildly modified substrata,
      employing well established microscopic and immunofluorescence techniques, namely
      the monitoring of cell adhesion and spreading, overall cell morphology,
      organization of FN receptors, and focal adhesions as well as FN matrix formation.
      The results suggest that cell interactions with hydrophobic polymer substrata are
      enhanced considerably when modified with hydrophilic and sterically demanding PEG
      moieties at a low surface coverage due to enhanced biologic activity of adsorbed
      and intercalated adhesive proteins such as FN.

PMID- 10906696
TI  - Tissue response to single-polymer fibers of varying diameters: evaluation of
      fibrous encapsulation and macrophage density.
AB  - An in vivo study was conducted to assess the sensitivity of fibrous capsule
      thickness and macrophage density to polymer fiber diameter. Single polypropylene
      fibers of diameters ranging from 2.1 to 26.7 microm were implanted in the
      subcutaneous dorsum of Sprague-Dawley rats. Results at 5 weeks demonstrated
      reduced fibrous capsule thickness for small fibers. Capsule thickness was 0.6 (+/
      1.8) microm, 11.7 (+/-12.0) microm, 20.3 (+/-11.6) microm, and 25.5 (+/-10.0)
      microm for fibers in the ranges of 2.1 to 5.9, 6.5 to 10.6, 11.1 to 15.8, and
      16.7 to 26.7 microm, respectively. Fibers very near to blood vessels had smaller
      capsules than did those with local vasculature further away. The macrophage
      density in tissue with fiber diameters 2.1 to 5.9 microm (23.03 +/- 8.67%) was
      comparable to that of unoperated contralateral control skin (18.72+/-10.06%). For
      fibers with diameters in the ranges of 6.5 to 10.6, 11.1 to 15.8, and 16.7 to
      26.7 microm, macrophage densities were 33.90+/-13.08%, 34.40+/-15.77%, and
      41.68+/-13.98%, respectively, all of which were significantly larger (p<0.002)
      than that for the control. The reduced fibrous capsule thickness and macrophage
      density for small fibers (<6 microm) compared with large fibers could be due to
      the reduced cell-material contact surface area or to a curvature threshold effect
      that triggers cell signaling. A next step will be to extend the analysis to
      meshes to evaluate fiber-spacing effects on small-fiber biomaterials.

PMID- 10906697
TI  - Corticothalamic projections from layer 5 of the vibrissal barrel cortex in the
      rat.
AB  - This study bears on the projections of layer 5 cells of the vibrissal sensory
      cortex to the somatosensory thalamus in rats. Small groups of cells were labeled
      with biotinylated dextran amine (BDA), and their axonal arborizations were
      individually reconstructed from horizontal sections counterstained for cytochrome
      oxidase. Results show that the vast majority ( approximately 95%) of layer 5
      axons that innervate the somatosensory thalamus are collaterals of corticofugal
      fibers that project to the brainstem. The anterior pretectal nucleus, the deep
      layers of the superior colliculus, and the pontine nuclei are among the
      structures most often coinnervated. In the thalamus, layer 5 axons terminate
      exclusively in the dorsal part of the posterior group (Po), where they form
      clusters of large terminations. Because dorsal Po projects to multiple cortical
      areas, we sought to determine whether all recipient areas return a layer 5
      projection to this part of the thalamus. Additional experiments using fluoro-gold
      and BDA injections provided evidence that the primary somatosensory area is the
      sole source of layer 5 projections to dorsal Po but that this thalamic region
      receives convergent layer 6 projections from the primary and second somatosensory
      areas and from the motor and insular cortices. These results show that layer 5
      projections do not overlap in associative thalamic nuclei, thus defining area
      related subdivisions. Furthermore, the coinnervation of brainstem nuclei by layer
      5 CT axons suggests that this pathway conveys to the thalamus a copy of the
      cortical output aimed at brainstem structures.

PMID- 10906698
TI  - Taste cells with synapses in rat circumvallate papillae display SNAP-25-like
      immunoreactivity.
AB  - SNAP-25 is a 25 kDa protein believed to be involved in the processes of membrane
      fusion and exocytosis associated with neurotransmitter release. In the present
      study we present evidence that SNAP-25-like immunoreactivity can be used as a
      marker for taste cells with synapses in rat circumvallate papillae. SNAP-25
      immunoreactivity is present in most intragemmal nerve processes and a small
      subset of taste cells. Intense immunoreactivity is associated with the nerve
      plexus located below the base of the taste bud. Of a total of 87 taste cells with
      synapses onto nerve processes, 80 of the presynaptic taste cells had SNAP-25
      immunoreactivity. The association of SNAP-25 immunoreactivity with taste cells
      possessing synapses suggests that these cells may be gustatory receptor cells.
      Because this SNAP-25 antibody can label taste cells with synapses, it may also
      serve as a useful tool for future studies correlating structure with function in
      the taste bud.

PMID- 10906699
TI  - Light and electron microscopic evidence for projections from the thalamic nucleus
      rotundus to targets in the basal ganglia, the dorsal ventricular ridge, and the
      amygdaloid complex in a lizard.
AB  - To elucidate the organization and evolution of the tectorotundotelencephalic
      pathways in birds and reptiles, we reinvestigated at both light and electron
      microscopic levels the efferent projections of nucleus rotundus in a lizard,
      using the sensitive tracer biotinylated dextran amine. Our results indicate that
      nucleus rotundus projects to targets in the basal ganglia (lateral parts of
      striatum and olfactory tubercle and possibly the globus pallidus), the anterior
      dorsal ventricular ridge (ADVR), and the amygdaloid complex (the central and
      possibly lateral amygdaloid nuclei). In these targets, the rotundal axon
      terminals establish asymmetric, presumably excitatory synaptic contacts, usually
      with dendrites of local cells. In the ADVR, the rotundal projection terminates in
      two separate radial regions showing distinct cytoarchitecture: 1) a dorsolateral
      region that extends radially from the dorsolateral ADVR ventricular surface to
      the ventral part of the lateral cortex and 2) the lateral part of a ventromedial
      region that extends radially from the dorsomedial and medial ADVR ventricle to a
      superficial area interposed between the dorsolateral ADVR and the striatum. These
      two ADVR regions have different connections with the thalamus and telencephalon,
      which suggests that they may be involved in different degrees of integration. Our
      study also suggests that the rotundal projection to the ventromedial ADVR field
      of lizards may be comparable to the rotundoectostriatal/periectostriatal
      projection of birds. The connections and pathways involving nucleus rotundus
      suggest that this nucleus conveys visual information which may play a role in
      visuomotor, emotional, and visceral functions.

PMID- 10906701
TI  - Monosynaptic projections from the lateral periaqueductal gray to the nucleus
      retroambiguus in the rhesus monkey: implications for vocalization and
      reproductive behavior.
AB  - The periaqueductal gray (PAG) is known to be essential for vocalization and
      reproductive behavior. The PAG controls components of these behaviors by means of
      projections to the nucleus retroambiguus (NRA), a group of premotor neurons in
      the caudal medulla oblongata. In the accompanying study (VanderHorst et al., 2000
      [accompanying study]), the NRA and its lumbosacral projections have been
      identified in the rhesus monkey. The present light and electron microscopical
      tracing study describes the PAG-NRA pathway in primates. To locate midbrain
      neurons projecting to the NRA, wheat germ agglutinin horseradish peroxidase (WGA
      HRP) was injected into the NRA in six monkeys. To determine the distribution
      pattern of PAG axons in the medulla oblongata, WGA-HRP was injected into the PAG
      and adjacent tegmentum in three additional monkeys. In one of these three
      monkeys, biotinylated dextran amine and cholera toxin subunit b were injected
      into the lumbosacral cord to retrogradely identify NRA neurons. The results show
      that a compact group of neurons in the medial part of the lateral PAG at the
      intercollicular level sends a dense projection to the NRA. The projection is
      bilateral with a clear ipsilateral predominance. At the ultrastructural level,
      there are monosynaptic contacts between PAG fibers and NRA neurons, including NRA
      neurons that project to the lumbosacral cord. The synaptic contacts were
      primarily asymmetrical and the labeled terminal profiles contained spherical and
      dense core vesicles. It is concluded that there exists a strong and direct PAG
      NRA pathway in the rhesus monkey. Because NRA neurons projecting to the lower
      lumbar cord are included, the PAG-NRA projection is likely to be involved not
      only in vocalization but also in other behaviors, such as receptive posture.

PMID- 10906700
TI  - Monosynaptic projections from the nucleus retroambiguus to motoneurons supplying
      the abdominal wall, axial, hindlimb, and pelvic floor muscles in the female
      rhesus monkey.
AB  - The nucleus retroambiguus (NRA) consists of premotor neurons in the caudal
      medulla. It is involved in expiration, vomiting, vocalization, and probably
      reproductive behavior by means of projections to distinct motoneuronal cell
      groups. Because no information is available about the NRA and its efferent
      pathways in primates, the present study examines NRA projections to the
      lumbosacral spinal cord in female rhesus monkeys. To identify the NRA, wheat germ
      agglutinin-horseradish peroxidase (WGA-HRP) was injected into the lumbosacral
      cord in three monkeys. To study the distribution of NRA axons in the lumbosacral
      cord, WGA-HRP injections were made into the NRA in seven monkeys. To identify
      motoneuronal cell groups receiving input from the NRA, the same seven monkeys
      also received cholera toxin subunit b (CTb) injections into different hindlimb,
      axial, and pelvic floor muscles. The results show that NRA neurons projecting to
      the lumbosacral cord are mainly located between 1 to 4 mm caudal to the obex.
      They send numerous axons to external oblique and pelvic floor motoneurons,
      whereas projections to iliopsoas and axial motoneurons are less numerous. The
      projections are bilateral, but show a clear contralateral predominance in the
      iliopsoas, axial, and pelvic floor motoneuronal cell groups. At the
      ultrastructural level, NRA-terminal profiles make asymmetrical contacts with
      labeled and unlabeled dendrites in these motoneuronal cell groups and contain
      large amounts of spherical and a few dense core vesicles. It is concluded that
      the NRA is well developed in the monkey and that there exists a direct pathway
      from the NRA to lumbosacral motoneurons in this species. The finding that the NRA
      projects to a somewhat different set of motoneuronal cell groups compared with
      other species fits the concept that it is not only involved in expiration-related
      activities but also in species specific receptive and submissive behavior.

PMID- 10906702
TI  - Metastasis-associated mts1 (S100A4) protein in the developing and adult central
      nervous system.
AB  - We have found recently that white matter astrocytes in the spinal cord
      constitutively express immunoreactivity for Mts1 (S100A4) protein and that this
      expression is up-regulated ipsilaterally after sciatic nerve or dorsal root
      injury. Here, we have studied the expression pattern of Mts1 throughout the rat
      central nervous system (CNS). We found Mts1 immunoreactivity in myelinated tracts
      such as the olfactory tract, optic nerve, corpus callosum, internal capsule,
      fimbria, and spinal cord funiculi but not in cerebellar white matter. Mts1
      immunoreactive (IR) cells were consistently astrocytic (glial fibrillary acidic
      protein positive). In addition to myelinated tracts, Mts1 immunoreactivity was
      also present in a few nonmyelinated or poorly myelinated areas, such as pituitary
      gland, olfactory bulb, and around the lateral ventricle. Based on location, three
      Mts1-IR astrocyte groups were distinguished: 1) astrocytes at the surfaces of the
      CNS, i.e., adjacent to the cerebrospinal fluid, organized perpendicularly to the
      bundles of axonal tracts; 2) astrocytes located in parallel to, and inserted
      between, axonal bundles; and 3) clusters of astrocytes around the lateral
      ventricle and in the olfactory bulb. We further analyzed the relationship between
      Mts1 immunoreactivity and the development of CNS fiber tracts by combining
      staining for Mts1 and myelin basic protein (MBP). Mts1 immunoreactivity appeared
      postnatally in recently myelinated areas. During the development of corpus
      callosum and the optic tract, Mts1 immunoreactivity was concentrated at the
      frontier of myelination. The developmental expression pattern suggests a role of
      Mts1-IR astrocytes in the maturation of myelinated fiber tracts. The preferential
      localization of Mts1 to the subpial region in the mature CNS suggests that Mts1
      participates in astrocyte-mediated CNS-cerebrospinal fluid exchange.

PMID- 10906703
TI  - Steroid regulation of octopamine expression during metamorphic development of the
      moth Manduca sexta.
AB  - Octopamine (OA), a biogenic amine similar to norepinephrine, has profound and
      well-documented actions on the nervous systems of invertebrates. In the insect,
      Manduca sexta, we examined the developmental plasticity of OA synthesis, studied
      its endocrine regulation, and observed previously undescribed OA-immunoreactive
      (ir) neurons. We found that levels of tyramine beta-hydroxylase (TbetaH), an
      essential enzyme for the biosynthesis of OA, increase during metamorphosis. Based
      on the established and influential roles of the steroid hormone 20
      hydroxyecdysone (20-HE) during development, we tested the hypothesis that
      increases in TbetaH levels and OA immunoreactivity are regulated by the rise in
      20-HE occurring during pupal-adult development. We determined that the levels of
      TbetaH in the terminal abdominal ganglion (neuromeres 6-9) remain at a constant
      level during pupal development and the early stages of adult development.
      Beginning at ca. pupal stage 8, however, the levels of TbetaH begin to rise,
      reaching a maximum level by pupal stage 12. By removing the source of ecdysteroid
      hormone through ligation, and by subsequent replacement of 20-HE via infusion, we
      found evidence indicating that the preadult rise of 20-HE is both necessary and
      sufficient for the increased levels of TbetaH. During the course of our study, we
      also identified previously unreported OA-ir neurons. In particular, adult
      specific OA-ir lateral cells were found, as were relatively small OA-ir dorsal
      median pairs that doubled in size during adult development. Abdominal ganglia not
      exposed to the preadult rise in 20-HE possessed neither the OA-ir lateral neurons
      nor the somatic growth of the smaller OA-ir median neurons. These newly described
      OA-ir neurons probably contribute to the steroid-induced elevations of TbetaH
      observed at the end of metamorphosis.

PMID- 10906704
TI  - Localization of l-afadin at puncta adhaerentia-like junctions between the mossy
      fiber terminals and the dendritic trunks of pyramidal cells in the adult mouse
      hippocampus.
AB  - We have recently found a novel cell-cell adhesion system at cadherin-based
      adherens junctions. This system consists of at least two components: nectin, an
      immunoglobulin-like cell adhesion molecule with Ca(2+)-independent homophilic
      binding activity, and l-afadin, an actin filament-binding protein that connects
      nectin to the actin cytoskeleton. In the present study, we investigated
      immunocytochemically the localization of l-afadin in the mouse hippocampus. At
      the light microscopic level, l-afadin immunoreactivity was demonstrated as
      flattened disks in the stratum lucidum of the CA3 area. By immunoelectron
      microscopy, signals for l-afadin were highly concentrated in a symmetrical manner
      at the puncta adhaerentia-like junctions between the mossy fiber terminals and
      the dendritic trunks of pyramidal cells. We furthermore immunostained the
      hippocampus with antibodies recognizing both l-afadin and s-afadin, a small
      splicing variant of l-afadin that is identical to AF-6. Immunoreactivity for l-
      and s-afadins was demonstrated not only as the flattened disks similar to that
      for l-afadin, but also as numerous fine dots widely distributed in all synaptic
      layers of the CA1 and CA3 areas. The latter finding may correspond with the
      recent report by Buchert et al. (1999, J. Cell. Biol. 144:361-371), who found
      that s-afadin (AF-6) and/or l-afadin was localized at the postsynaptic membranes
      of asymmetric synaptic junctions. Our present results indicate that l- and s
      afadins are differentially distributed in the hippocampus and suggest that l
      afadin localized at the puncta adhaerentia-like junctions in the mossy fiber
      terminals may regulate the structural and functional organization of these
      complex synaptic structures.

PMID- 10906705
TI  - Basic fibroblast growth factor inhibits cell proliferation in cultured avian
      inner ear sensory epithelia.
AB  - Postembryonic production of inner ear hair cells occurs after insult in
      nonmammalian vertebrates. Recent studies suggest that the fibroblast family of
      growth factors may play a role in stimulating cell proliferation in mature inner
      ear sensory epithelium. Effects of acidic fibroblast growth factor (FGF-1) and
      basic fibroblast growth factor (FGF-2) were tested on progenitor cell division in
      cultured auditory and vestibular sensory epithelia taken from posthatch chickens.
      The effects of heparin, a glycosaminoglycan that often potentiates the effects of
      the FGFs, were also assessed. Tritiated-thymidine autoradiographic techniques and
      5-bromo-2;-deoxyuridine (BrdU) immunocytochemistry were used to identify cells
      synthesizing DNA. The terminal deoxynucleotidyl transferase (TdT)-mediated
      deoxyuridine triphosphate (dUTP)-biotin nick-end-label (TUNEL) method was used to
      identify apoptotic cells. TUNEL and overall counts of sensory epithelial cell
      density were used to assess possible cytotoxic effects of the growth factors. FGF
      2 inhibited DNA synthesis in vestibular and auditory sensory epithelia and was
      not cytotoxic at the concentrations employed. FGF-1 did not significantly alter
      sensory epithelial cell proliferation. Heparin by itself inhibited DNA synthesis
      in the vestibular sensory epithelia and failed to potentiate the effects of FGF-1
      or FGF-2. Heparin was not cytotoxic at the concentrations employed. Results
      presented here suggest that FGF-2 may be involved in inhibiting cell
      proliferation or stimulating precursor cell differentiation in avian inner ear
      sensory epithelia.

PMID- 10906706
TI  - Disabled-1 is expressed in type AII amacrine cells in the mouse retina.
AB  - The organization of several laminated structures in the brain is controlled by a
      signaling pathway activated by Reelin, a large glycoprotein secreted by pioneer
      neurons in the developing brain. Reelin binds to transmembrane receptors,
      including VLDLR and ApoER2, and stimulates tyrosine phosphorylation of Disabled-1
      (Dab1), which associates with an NPxY motif present in the cytoplasmic domain of
      the receptors. Disruption of reelin, dab1, or both the vldr and apoer2 genes
      results in similar cell positioning defects in laminated brain regions including
      the cerebellum, hippocampus, and cerebral cortex. Although retinal ganglion cells
      express reelin during development, there is no obvious disruption of cell
      positioning in the retina of reeler mice. Here, we examine the expression pattern
      of Dab1 as a first step toward understanding the function of the Reelin signaling
      pathway in neural retina. Immunohistochemical analysis of the adult retina
      revealed that Dab1 is expressed in a specific type of amacrine cell. These cells
      display a narrow dendritic field and they project to two distinct sublaminae
      within the inner plexiform layer. Dab1 co-localizes with the high-affinity
      glycine transporter, indicating that these amacrine cells are glycinergic. Cells
      that express Dab1 are surrounded by dopaminergic fibers originating from wide
      field amacrine cells. These features are characteristic of type AII amacrine
      cells described in other mammalian species. Analysis of the retina at several
      stages of development revealed that Dab1 is expressed shortly after birth during
      the time at which AII amacrine cells extend neurites and form synaptic
      connections in the inner retina. This raises the possibility that the Reelin/Dab1
      signaling pathway contributes to formation of intraretinal circuitry in the
      neural retina.

PMID- 10906707
TI  - Identification of the cellular target for eclosion hormone in the abdominal
      transverse nerves of the tobacco hornworm, Manduca sexta.
AB  - The isolated abdominal central nervous system of Manduca sexta undergoes an
      increase in cyclic GMP (cGMP) when exposed to the insect peptide eclosion hormone
      (EH) before pupal ecdysis. Previously, cGMP immunocytochemistry revealed that the
      EH-stimulated increase in cGMP was contained in numerous filamentous processes
      within the transverse nerve associated with each abdominal ganglion. These
      processes seemed to be the axons of neurosecretory cells projecting to this
      neurohemal organ. In the present paper, we now show that the EH-stimulated cGMP
      is not present in neurosecretory terminals. There is no colocalization of the EH
      stimulated cGMP with immunoreactivity of two peptides, known to be present in
      axons in the transverse nerves. Furthermore, there is no colocalization of EH
      stimulated cGMP with the synaptic vesicle protein, synaptotagmin. The
      neurosecretory axons are localized to a narrow band at the anterior margin of the
      transverse nerve, whereas the cellular elements showing an EH-stimulated cGMP
      increase are primarily present in the posterior region. There are two cell types
      in this region: a granular and a nongranular type. The cGMP immunoreactivity
      seems to be contained within the nongranular type. During adult development, the
      cells of the posterior compartment spread in a thin layer between the transverse
      and dorsal nerves, become positive for myosin immunoreactivity between pupal
      stages 5 and 8, and seem to form the adult ventral diaphragm muscles. We conclude
      that the EH-sensitive filaments in the transverse nerves of Manduca are most
      likely to be intrinsic cells that subsequently develop into the ventral diaphragm
      muscles of the adult.

PMID- 10906708
TI  - Organization and significance of neurons that detect change of visual depth in
      the hawk moth Manduca sexta.
AB  - Visual stimuli representing looming or receding objects can be decomposed into
      four parameters: change in luminance; increase or decrease of area; increase or
      decrease of object perimeter length; and motion of the object's perimeter or
      edge. This paper describes intracellular recordings from visual neurons in the
      optic lobes of Manduca sexta that are selectively activated by certain of these
      parameters. Two classes of wide-field neurons have been identified that respond
      selectively to looming and receding stimuli. Class 1 cells respond to parameters
      of the image other than motion stimuli. They discriminate an approaching or
      receding disc from an outwardly or inwardly rotating spiral, being activated only
      by the disc and not by the spiral. Class 2 neurons respond to moving edges. They
      respond both to movement of the spiral and to an approaching or receding disc.
      These two classes are further subdivided into neurons that are excited by image
      expansion (looming) and are inhibited by image contraction (antilooming). Class 2
      neurons also respond to horizontal and vertical movement of gratings over the
      retina. Stimulating class 1 and 2 neurons with white discs against a dark
      background results in the same activation as stimulation with dark discs against
      a white background, demonstrating that changes in luminance play no role in the
      detection of looming or antilooming. The present results show that the two types
      of looming-sensitive neurons in M. sexta use different mechanisms to detect the
      approach or retreat of an object. It is proposed that cardinal parameters for
      this are change of perimeter length detected by class 1 neurons and expansion or
      contraction visual flow fields detected by class 2 neurons. These two classes
      also differ with respect to their polarity, the former comprising centripetal
      cells from the optic lobes to the midbrain, the latter comprising centrifugal
      neurons from the midbrain to the optic lobes. The significance of these
      arrangements with respect to hovering flight is discussed.

PMID- 10906709
TI  - Early morphologic alterations in trophically deprived neuronal death in vitro
      occur without alterations in cytoplasmic Ca(2+).
AB  - Morphologic and functional parameters altered during neuronal death were
      investigated in chick ciliary ganglion (CG) neurons in vitro isolated from
      embryonic day 8 (E8, stage 34). Neurons were separated from nonneuronal cells to
      investigate their inherent cell death program and were cultured with or without
      trophic support (choroid, iris, pigment epithelium) from their appropriate target
      tissue. The cell death process was characterized with investigations focused on
      the earliest events at the onset of commitment to cell death at 11 hours after
      plating. Initial morphologic changes in the process of cell death were
      cytoplasmic; swelling, dendritic retraction, blebbing, vacuolization, which are
      all characteristics of necrosis. Later, nuclear chromatin condensation occurred,
      a characteristic of apoptosis. An increase in membrane permeability was measured
      earlier at 8 hours. During these alterations (associated with the initiation of
      cell death) single cell analysis was performed to evaluate mobile Ca(2+) changes
      in the same trophically deprived neurons during the course of the death process;
      Ca(2+) levels remained at 50 nM. Transient Ca(2+) entry was buffered in control
      and deprived cells at 13 hours but with different parameters. During the
      execution stage of death mobile Ca(2+) levels were variable. In this final stage
      of cell death, neurons demonstrated nuclear damage, cytosol disintegration, or
      morphology sharing both characteristics. These observations define embryonic CG
      cell death in vitro as neither purely apoptotic nor necrotic but a form of that
      exhibits features of both. These results also demonstrate a disassociation of
      changes in cytosolic Ca(2+) from both CG neuronal survival and trophically
      deprived cell death in vitro.

PMID- 10906710
TI  - Mitotically active cells that generate neurons and astrocytes are present in
      multiple regions of the adult mouse hippocampus.
AB  - Previous studies of the adult hippocampus of rodents and primates have reported
      neuro- and gliogenesis restricted to the region of the dentate gyrus. In the
      present study, by employing a prolonged bromodeoxyuridine (BrdU) labeling
      protocol that attempts to account for cytokinetic changes as an animal ages, we
      have identified mitotically active cells in multiple regions of the hippocampus,
      especially in Ammon's horn, of the adult mouse. Immediately following the
      labeling period, the BrdU-labeled cells did not express known markers for neurons
      and astrocytes. Subsequent analysis at 3-24 weeks after labeling demonstrated
      BrdU-labeled neurons and glia in these regions of the hippocampus. Although neuro
      and gliogenesis in the adult mammalian hippocampus have been reported
      previously, these results demonstrate that the phenomenon is not limited to the
      region of the dentate gyrus, but rather extends into Ammon's horn. Furthermore,
      it suggests that ongoing cell production, albeit discrete and limited in nature,
      may be widespread in the adult mammalian central nervous system.

PMID- 10906711
TI  - Pallial and subpallial derivatives in the embryonic chick and mouse
      telencephalon, traced by the expression of the genes Dlx-2, Emx-1, Nkx-2.1, Pax
      6, and Tbr-1.
AB  - Pallial and subpallial morphological subdivisions of the developing chicken
      telencephalon were examined by means of gene markers, compared with their
      expression pattern in the mouse. Nested expression domains of the genes Dlx-2 and
      Nkx-2.1, plus Pax-6-expressing migrated cells, are characteristic for the mouse
      subpallium. The genes Pax-6, Tbr-1, and Emx-1 are expressed in the pallium. The
      pallio-subpallial boundary lies at the interface between the Tbr-1 and Dlx-2
      expression domains. Differences in the expression topography of Tbr-1 and Emx-1
      suggest the existence of a novel "ventral pallium" subdivision, which is an Emx-1
      negative pallial territory intercalated between the striatum and the lateral
      pallium. Its derivatives in the mouse belong to the claustroamygdaloid complex.
      Chicken genes homologous to these mouse genes are expressed in topologically
      comparable patterns during development. The avian subpallium, called
      "paleostriatum," shows nested Dlx-2 and Nkx-2.1 domains and migrated Pax-6
      positive neurons; the avian pallium expresses Pax-6, Tbr-1, and Emx-1 and also
      contains a distinct Emx-1-negative ventral pallium, formed by the massive domain
      confusingly called "neostriatum." These expression patterns extend into the
      septum and the archistriatum, as they do into the mouse septum and amygdala,
      suggesting that the concepts of pallium and subpallium can be extended to these
      areas. The similarity of such molecular profiles in the mouse and chicken pallium
      and subpallium points to common sets of causal determinants. These may underlie
      similar histogenetic specification processes and field homologies, including some
      comparable connectivity patterns.

PMID- 10906712
TI  - Regional and cellular localization of the neuroendocrine prohormone convertases
      PC1 and PC2 in the rat central nervous system.
AB  - PC1 and PC2 are two major enzymes involved in the processing of protein
      precursors directed to the regulated secretory pathway. Whereas transcripts
      encoding both enzymes are widely distributed in the central nervous system,
      information regarding the localization of proteins themselves is still lacking.
      In an attempt to gain insight into the neurobiologic roles of PC1 and PC2, both
      enzymes were immunolocalized in the rat brain by using C-terminally directed
      antibodies, which respectively recognize the 87-kDa PC1 and the 75 and 68-kDa PC2
      forms. Adjacent sections immunoreacted with PC1 or PC2 antibodies exhibited
      selective patterns of immunostaining in regions well characterized with respect
      to their biosynthesis of multiple neuropeptides such as the cerebral cortex,
      hippocampus, and hypothalamus. PC1 signal intensity was generally weaker than
      that of PC2, although both enzymes displayed extensive overlapping patterns of
      expression. As assessed by double-labeling experiments at the cellular level, PC1
      and PC2 immunoreactive signals were localized within the trans-Golgi network and
      nerve terminals, in keeping with the biosynthetic pathways of neuropeptides.
      Immunoreactive fibers were detected in many areas throughout the brain but were
      particularly densely distributed in the hypothalamus and the brainstem. Both
      enzymes were also localized within dendrites of numerous neurons, supporting the
      hypothesis that dendritic neuropeptide maturation and release may occur in a
      large number of brain regions. Taken together, our results provide new evidence
      that both convertases are efficiently targeted to the neuronal regulated
      secretory pathway and are well poised to process protein precursors in
      biologically active end-products within the mammalian brain.

PMID- 10906713
TI  - Immunohistochemical evidence for the involvement of protein convertases 5A and 2
      in the processing of pro-neurotensin in rat brain.
AB  - The neuropeptides/neurotransmitters neurotensin (NT) and neuromedin (NN) are
      synthesized by endoproteolytic cleavage of a common inactive precursor, pro
      NT/NN. In vitro studies have suggested that the prohormone convertases PC5A and
      PC2 might both be involved in this process. In the present study, we used dual
      immunohistochemical techniques to determine whether either one or both of these
      two convertases were co-localized with pro-NT/NN maturation products and could
      therefore be involved in the physiological processing of this propeptide in rat
      brain. PC2-immunoreactive neurons were present in all regions immunopositive for
      NT. All but three regions expressing NT were also immunopositive for PC5A. Dual
      localization of NT with either convertase revealed that NT was extensively co
      localized with both PC5A and PC2, albeit with regional differences. These results
      strongly suggest that PC5A and PC2 may play a key role in the maturation of pro
      NT/NN in mammalian brain. The regional variability in NT/PC co-localization
      patterns may account for the region-specific maturation profiles previously
      reported for pro-NT/NN. The high degree of overlap between PC5A and PC2 in most
      NT-rich areas further suggests that these two convertases may act jointly to
      process pro-NT/NN. At the subcellular level, PC5A was largely co-localized with
      the mid-cisternae Golgi marker MG-160. By contrast, PC2 was almost completely
      excluded from MG-160-immunoreactive compartments. These results suggest that
      PC5A, which is particularly efficient at cleaving the two C-terminal-most
      dibasics of pro-NT/NN, may be acting as early as in the Golgi apparatus to
      release NT, whereas PC2, which is considerably more active than PC5A in cleaving
      the third C-terminal doublet, may be predominantly involved further distally
      along the secretory pathway to release NN.

PMID- 10906714
TI  - Developmental cell death in dopaminergic neurons of the substantia nigra of mice.
AB  - Dopaminergic neurons in the substantia nigra pars compacta (SNpc) undergo natural
      cell death during development in rats. Controversy exists as to the occurrence of
      this phenomenon in SNpc dopaminergic neurons in the developing mouse. Herein, by
      using an array of morphologic techniques, we show that many SNpc neurons fulfill
      the criteria for apoptosis and that the number of apoptotic neurons in the SNpc
      vary in a time-dependent manner from postnatal day 2 to 32. These dying neurons
      also show evidence of DNA fragmentation, of activated caspase-3, and of cleavage
      of beta-actin. Some, but not all of the SNpc apoptotic neurons still express
      their phenotypic marker tyrosine hydroxylase, confirming their dopaminergic
      nature. Consistent with the importance of target-derived trophic support in
      modulating developmental cell death, we demonstrate that destruction of intrinsic
      striatal neurons by a local injection of quinolinic acid (QA) dramatically
      enhances the magnitude of SNpc apoptosis and results in a lower number of adult
      SNpc dopaminergic neurons. Strengthening the apoptotic nature of the observed
      SNpc developmental cell death, we demonstrate that overexpression of the anti
      apoptotic protein Bcl-2 attenuates both natural and QA-induced SNpc apoptosis.
      The present study provides compelling evidence that developmental neuronal death
      with a morphology of apoptosis does occur in the SNpc of mice and that this
      process plays a critical role in regulating the adult number of dopaminergic
      neurons in the SNpc.

PMID- 10906715
TI  - Distribution of nociceptin/orphanin FQ precursor protein and receptor in brain
      and spinal cord: a study using in situ hybridization and X-gal histochemistry in
      receptor-deficient mice.
AB  - Nociceptin/orphanin FQ (N/OFQ) is an opioid-like heptadecapeptide agonist for the
      opioid receptor homolog, N/OFQ receptor. To explore the precise distribution of
      the peptide-receptor system, the authors examined the brain and spinal cord from
      receptor-deficient mice bearing the targeted mutation (morc(m1)), a lacZ
      insertional mutation in the N/OFQ receptor gene. Precursor protein N/OFQ
      (preproN/OFQ) mRNA was detected by using in situ hybridization, and the N/OFQ
      receptor was detected by using X-gal histochemistry. The N/OFQ receptor reflected
      by lacZ expression was observed at high levels in the dentate gyrus, lateral
      septum, subparafascicular thalamic nucleus, medial preoptic area, median preoptic
      nucleus, ventromedial preoptic nucleus, anterior hypothalamic area,
      paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, auditory
      brainstem nuclei, pontine dorsal tegmentum, and nucleus of the solitary tract. In
      situ detection of the N/OFQ receptor mRNA by digoxigenin-labeled riboprobes
      coupled with tyramide signal amplification in normal and wild-type mice resulted
      in the regional distribution paralleling the lacZ expression in these regions.
      PreproN/OFQ mRNA was expressed at high levels in the subparafascicular thalamic
      nucleus, central gray, central tegmental field, auditory brainstem nuclei, caudal
      spinal trigeminal nucleus, and spinal dorsal horn. Furthermore, variable levels
      of expression of the peptide and receptor were seen in distinct sites of the
      brain and spinal cord. These data indicate a correspondence of the peptide and
      the receptor in local distribution at limbic, hypothalamic, and brainstem sites.
      Together with concurrent physiologic and behavioral studies in mutant mice, the
      results suggest functional roles for the N/OFQ system, including the central
      regulation of learning and memory, hearing ability, water balance, food intake,
      and blood pressure.

PMID- 10906716
TI  - Sensory organ generation in the chicken inner ear: contributions of bone
      morphogenetic protein 4, serrate1, and lunatic fringe.
AB  - The chicken inner ear is a remarkably complex structure consisting of eight
      morphologically distinct sensory organs. Unraveling how these sensory organs are
      specified during development is key to understanding how such a complex structure
      is generated. Previously, we have shown that each sensory organ in the chicken
      inner ear arises independently in the rudimentary otocyst based on Bone
      morphogenetic protein 4 (Bmp4) expression. Here, we compare the expression of
      Bmp4 with two other putative sensory organ markers, Lunatic Fringe (L-fng) and
      chicken Serrate1 (Ser1), both of which are components of the Notch signaling
      pathway. L-fng and Ser1 expression domains were asymmetrically distributed in the
      otic cup. At this early stage, expression of L-fng is similar to Delta1 (Dl1), in
      an anteroventral domain apparently corresponding to the neurogenic region, while
      Ser1 is expressed at both the anterior and posterior poles. By the otocyst stage,
      the expression of both L-fng and Ser1 largely coincided in the medial region. All
      presumptive sensory organs, as identified by Bmp4 expression, arose within the
      broad L-fng- and Ser1-positive domain, indicating the existence of a sensory
      competent region in the rudimentary otocyst. In addition, there is a qualitative
      difference in the levels of expression between L-fng and Ser1 such that L-fng
      expression was stronger in the ventral anterior, whereas Ser1 was stronger in the
      dorsal posterior region of this broad domain. This early difference in expression
      may presage the differences among sensory organs as they arise from this sensory
      competent zone.

PMID- 10906717
TI  - Bilateral growth-related protein expression suggests a transient increase in
      regenerative potential following brain trauma.
AB  - The potential of mature central nervous system (CNS) neurons to regenerate after
      injury represents a fundamental issue in neurobiology. The regional expression of
      proteins associated with axonal elongation, such as microtubule-associated
      protein 1B (MAP1B), its phosphorylated isoform (MAP1B-P), growth-associated
      protein 43 (GAP-43), and polysialylated neural cell-adhesion molecule (PSA-NCAM),
      was examined using immunohistochemistry from 24 hours to 2 months following
      lateral fluid percussion brain injury of moderate severity (2.4-2.6 atmospheres)
      in anesthetized rats. Uninjured (control) rats were subjected to anesthesia and
      surgery without injury or were subjected to anesthesia alone. Within the site of
      maximal injury, only increases in MAP1B and MAP1B-P were observed. Increased
      immunoreactivity was observed bilaterally for all growth-related proteins that
      were evaluated. By 24 hours postinjury, MAP1B and MAP1B-P increased within the
      cortex (P < 0.01) and the hippocampus (P < 0.001), whereas MAP1B-P also was
      elevated in the thalamus (P < 0.05). Within the dentate gyrus, increased
      immunoreactivity was observed for all proteins examined. By 48 hours postinjury,
      GAP-43 was elevated bilaterally within the inner molecular layers of the dentate
      gyrus (P < 0.005) and within the stratum lacunosum moleculare (P < 0.01), the
      stratum radiatum (P < 0. 005), and the stratum oriens (P < 0.05) of the
      hippocampus. Increased numbers of PSA-NCAM-labeled neurons were observed in the
      granule cell layers of the dentate gyrus from 48 hours through 2 weeks postinjury
      (P < 0.0005). The bilateral nature of increased expression of growth-related
      proteins differs from unilateral patterns of neuronal degeneration previously
      characterized for the lateral fluid-percussion model of brain injury. Taken
      together, these results suggest the existence of a temporary posttraumatic state
      in which the CNS may have increased regenerative potential. Enhancement of such a
      response may be one therapeutic strategy in treating CNS injury.

PMID- 10906718
TI  - Chondroitin sulfate proteoglycan expression pattern in hippocampal development:
      potential regulation of axon tract formation.
AB  - A variety of molecular influences in the extracellular matrix (ECM) interact with
      developing axons to guide the formation of hippocampal axon pathways. One of
      these influences may be chondroitin sulfate proteoglycans (CSPGs), which are
      known to inhibit axonal extension during development and following central
      nervous system injury. In this study, we examined the role of CSPGs and cell
      adhesion molecules in the regulation of axon tract formation during hippocampal
      development. We used indirect immunofluorescence to examine the developmental
      pattern of CSPG expression relative to axon tracts that express the cell adhesion
      molecule L1. Additionally, we used dissociated and explant cell cultures to
      examine the effects of CSPGs on hippocampal axon development in vitro. In vivo,
      we found that the CSPG neurocan is expressed throughout the alveus, neuropil
      layers, and parts of the dentate gyrus from E16 to P2. The CSPG phosphacan is
      expressed primarily in the neuropil layers at postnatal stages. After E18,
      intense labeling of neurocan was observed in regions of the alveus surrounding L1
      expressing axon fascicles. In vitro, axons from brain regions that project
      through the alveus during development would not grow across CSPG substrata, in a
      concentration-dependent manner. In addition, hippocampal axons from dissociated
      neuron cultures only traveled across CSPG substrata as fasciculated axon bundles.
      These findings implicate CSPG in the regulation of axon trajectory and
      fasciculation during hippocampal axon tract formation.

PMID- 10906719
TI  - Calbindin-immunoreactive neurons in the reticular formation of the rat brainstem:
      catecholamine content and spinal projections.
AB  - Calbindin-D28k (calbindin) is a calcium-binding protein that is distributed
      widely in the rat brain. The localisation of calbindin immunoreactivity in the
      medulla oblongata and its colocalisation with adrenaline-synthesising neurons
      [phenylethanolamine-N-methyltransferase-immunoreactive (PNMT-IR)] was examined
      (Granata and Chang [1994] Brain Res. 645:265-277). However, detailed information
      about the distribution of calbindin-IR neurons in the reticular formation of the
      medulla oblongata in particular is lacking. In this report, the authors address
      this issue with an emphasis on the quantitation of calbindin-IR neurons,
      catecholamine neurons [tyrosine hydroxylase (TH)-IR, or PNMT-IR], and spinally
      projecting neurons in the ventral brainstem. Rats received injections of the
      retrograde tracing agent cholera toxin B (CTB) into the thoracic spinal cord or
      into the superior cervical ganglion. Immunocytochemistry was used to reveal
      calbindin, TH, PNMT, and CTB immunoreactivity. Ten calbindin-IR cell groups were
      identified within the pontomedullary reticular formation. Seven previously
      undescribed but distinct clusters of calbindin-IR neurons were found. Within the
      ventral pons, a population of calbindin-IR neurons occurred dorsal but adjacent
      to the A5 cell group. These calbindin-IR neurons did not contain either TH or
      PNMT immunoreactivity, and few if any of these neurons projected to the spinal
      cord. A distinct group of calbindin-IR neurons was present in the ventral
      medulla. Seventy-five percent of these calbindin-IR neurons contained TH
      immunoreactivity, 45% contained PNMT immunoreactivity, and 21% were spinally
      projecting neurons. Spinally projecting, calbindin-IR neurons were a
      subpopulation of PNMT-IR cells. In the caudal ventral medulla, no TH-IR or PNMT
      IR cells were calbindin-IR. In the intermediolateral cell column, close
      appositions of calbindin-IR terminals on identified sympathetic preganglionic
      neurons as well as calbindin-IR synapses indicated that these neurons may affect
      directly the sympathetic outflow. The results demonstrate for the first time the
      existence of a new subpopulation of spinally projecting, PNMT-IR neurons in the
      rostral ventrolateral medulla.

PMID- 10906720
TI  - Lipids, lipophilic drugs, and oral drug delivery-some emerging concepts.
AB  - Lipid-based dose forms, which encompass a wide variety of compositional and
      functional characteristics, can be advantageously utilized for the formulation of
      lipophilic drugs. There has been a traditional reluctance to develop lipid-based
      dose forms due to potential problems of chemical and physical instability, and a
      paucity of knowledge regarding formulation design algorithms and technology
      transfer issues. However, there is a current resurgence of interest in lipid
      based dose forms due to potential commercial and pharmaceutical benefits, and the
      industry trend towards the discovery/development of increasingly hydrophobic (and
      potent) new chemical entities. This mini-review describes some emerging
      formulation and biopharmaceutic strategies that hold promise for better
      understanding how to design and evaluate lipid-based dose forms.

PMID- 10906721
TI  - Biomedical application of immobilized enzymes.
AB  - Reports on chemical immobilization of proteins and enzymes first appeared in the
      1960s. Since then, immobilized proteins and enzymes have been widely used in the
      processing of variety of products and increasingly used in the field of medicine.
      Here, we present a review of recent developments in immobilized enzyme use in
      medicine. Generally speaking, the use of immobilized enzyme in medicine can be
      divided into two major categories: biosensors and bioreactors. A brief overview
      of the evolution of the biosensor and bioreactor technology, of currently
      existing applications of immobilized enzymes, of problems that researchers
      encountered, and of possible future developments will be presented.

PMID- 10906722
TI  - Dry adsorbed emulsion: 1. Characterization of an intricate physicochemical
      structure.
AB  - A recent solid pharmaceutical form called "Dry Adsorbed Emulsion" (DAE) was
      characterized in morphological and structural fields. A DAE is an intricate
      system initiated by a water-in-oil emulsion including the active drug (i.e.,
      theophylline). Each emulsion phase is adsorbed on pulverulent adsorbents with a
      suitable polarity (silica) to obtain a free-flowing powder with nonporous
      particles of size from 125 to 710 microm, with small specific surface area and a
      spherical shape. Different methods, such as scanning electron microscopy combined
      with chemical microanalysis, dying tests, and electron spin resonance studies,
      allow the formulator to follow the behavior of DAE aqueous and oily phases during
      the manufacturing process and then to set up a structural model for DAE
      particles. These DAE particles appear to be made up of a random pack of
      hydrophilic and hydrophobic particles, containing a liquid phase adsorbed on
      silica by weak bonds.

PMID- 10906723
TI  - Determination of serum protein binding affinity of inhibitors from analysis of
      concentration-response plots in biochemical activity assays.
AB  - Serum protein binding is a common problem with synthetic molecules designed as
      enzyme and receptor inhibitors for in vivo clinical use. The theoretical basis of
      a simple method is described. In this method, the dissociation constant for serum
      protein binding may be determined from analysis of the shift in apparent IC(50)
      (concentration at which 50% inhibition of activity is observed) caused by the
      presence of varying concentrations of serum (or individual serum proteins) in
      biochemical activity assays. Knowledge of the serum protein dissociation constant
      and the serum concentration of the binding protein can be used to predict the
      amount of free compound available in vivo after dosing to achieve a specific
      total concentration of compound in the blood stream.

PMID- 10906724
TI  - Determination of the free fraction and relative free fraction of drugs strongly
      bound to plasma proteins.
AB  - This report describes a new method for the determination of protein binding and
      relative protein binding (ratio of f(u) for different species) for compounds
      strongly bound to proteins. The method used is based on the distribution of the
      drug in plasma water, plasma proteins, and blood cells. Incubations were
      performed in diluted plasma. In diluted plasma, the erythrocyte/plasma
      distribution was determined with greater precision than in undiluted plasma.
      Formulae were derived for calculating f(u) in undiluted plasma based on the f(u)
      values determined in diluted plasma. These formulae are also valid in the event
      of more than one independent binding site in plasma. All incubations with plasma
      of different species were performed using rat erythrocyte suspensions, thereby
      making it possible for relative f(u) values in different species to be calculated
      without knowing the absolute free fractions. This method avoids the determination
      of the erythrocyte/buffer distribution in cases where it is sufficient to know
      relative f(u) values (e.g., exposure comparisons). Relative protein binding can
      also be quantified for compounds that tend to adsorb to surfaces of vials or test
      tubes, thus avoiding errors caused by adsorption when quantifying the drug in a
      protein-free aqueous solution. This method was validated by making comparisons of
      free fraction values obtained by the method herein described with those obtained
      by either ultrafiltration or equilibrium dialysis for two compounds that bind
      predominantly to albumin and another compound that binds to alpha(1)-acid
      glycoprotein. The results confirm our method produces identical free fractions in
      comparison with other established techniques. In addition, the range of
      applications of our method is much wider.

PMID- 10906725
TI  - Effect of dietary oil intake on hepatic cytochrome P450 activity in the rat.
AB  - The objective of the present study was to investigate whether or not different
      dietary oils, commonly used as drug vehicles, alter hepatic microsomal drug
      metabolism in the rat. Male adult Sprague-Dawley rats were administered 1 mL/kg/d
      of either corn, olive, sesame, or soybean oil via oral gavage for 7 days. An
      additional rat group was given an equal volume of water each day to serve as a
      control. We found that the hepatic cytochrome P450 (CYP) 3A2 protein level
      increased by 16% (p < 0.01) in rats given soybean oil compared with control rats.
      In contrast, CYP2C11 protein levels decreased by 32% (p < 0.01) in the corn oil
      group and by 31% (p < 0. 01) in rats given olive oil. The changes in the in vitro
      production of 6beta- and 2alpha-hydroxytestosterone, markers of CYP3A2 and 2C11
      activities, respectively, were consistent with their protein levels, although not
      statistically different than controls. The results demonstrate that dietary oils
      may have differential effects on specific hepatic CYP isoforms and may add to the
      variability in metabolism when xenobiotics are administered using dietary oils as
      vehicles.

PMID- 10906726
TI  - A novel apparatus for rat in vivo evaluation of dry powder formulations for
      pulmonary administration.
AB  - The lungs have attracted increasing attention as a site for administration of
      drugs, including macromolecules that are poorly absorbed from the intestine.
      There have been a number of basic studies in which peptide solutions were
      administered to experimental animals via the lungs. Although there have been
      several studies of pulmonary peptide absorption from dry powder formulations, a
      simpler and more inexpensive apparatus for administration of dry powders would
      enhance rapid screening of the formulations. In this study, we developed a simple
      apparatus to disperse dry powders. The apparatus has two 3-way stopcocks; one
      allows dispersal of powders at a constant pressure and airflow, and the other
      allows rats to breathe before and after administration. Dry powders of
      fluorescein (FL) and FITC-dextran (FD4) were manufactured by the spray-drying
      technique. The effects of operating conditions on the absorption of these model
      drugs were examined in rats. The C(max) for FL from dry powder was lower than
      that from solution and mean residence time was extended, suggesting that
      dissolution was the rate-determining step for FL absorption from dry powder. For
      FD4, the rate of absorption may not be regulated by dissolution but by epithelial
      transport. Absorption of insulin from spray-dried powder via the rat trachea was
      investigated using this apparatus. Intratracheally administered spray-dried
      insulin powder decreased plasma glucose level to a greater extent than spray
      dried insulin solution administered via the same route. Thus, the apparatus is
      simple, inexpensive, and useful for rapid screening of dry powder formulations.

PMID- 10906727
TI  - Refolding a glutamine synthetase truncation mutant in vitro: identifying superior
      conditions using a combination of chaperonins and osmolytes.
AB  - A new method that uses a combination of bacterial GroE chaperonins and cellular
      osmolytes for in vitro protein folding is described. With this method, one can
      form stable chaperonin-protein folding intermediate complexes to prevent
      deleterious protein aggregation and, using these complexes, screen a large array
      of osmolyte solutions to rapidly identify the superior folding conditions. As a
      test substrate, we used GSDelta468, a truncation mutant of bacterial glutamine
      synthetase (GS) that cannot be refolded to significant yields in vitro with
      either chaperones or osmolytes alone. When our chaperonin/osmolyte method was
      employed to identify and optimize GSDelta468 refolding conditions, 67% of enzyme
      activity was recovered, comparable with refolding yields of wild type GS. This
      method can potentially be applied to the refolding of a broad spectrum of
      proteins.

PMID- 10906728
TI  - Pharmacodynamic effects of bezafibrate and niacin combination: implications of
      the mode of administration.
AB  - The goal of this investigation was to optimize antilipid therapy by utilizing the
      combined activity of two lipid-lowering agents, niacin and bezafibrate, and
      improve their efficacy by targeting them to their presumed presystemic site(s) of
      action. Thus, continuous duodenal (IGI) administration of the drug combination
      should augment their efficacy in comparison with intermittent oral treatment.
      Three hyperlipidemic rat models were studied: Models A and B were based on
      cholesterol-enriched diets and Model C was based on on acute hyperlipidemia
      induced by triton injection. Continuous IGI administration of the drug
      combination [bezafibrate, 30mg/kg/day, and niacin, 40 mg/kg/day for 3 days
      (Models A and B) or for 18 h (Model C)] produced significantly greater lowering
      of total cholesterol and triglycerides and elevation of high-density lipoprotein
      (HDL) cholesterol in comparison with intermittent oral administration of the same
      doses either given individually or in combination (Models A and B). Similar
      results were found in Model C for the IGI administration of the drug combination
      in contrast to oral and also to intravenous infusions. The results indicate that
      the combination of bezafibrate and niacin produces a significant hypolipidemic
      response, with major site(s) of action located presystemically. Because a slow
      release matrix tablet of the drug combination resulted in a similar magnitude of
      effect as the IGI administration, the present study provides a pharmacodynamic
      rationale for the use of a slow-release low-dose niacin-bezafibrate combination.

PMID- 10906729
TI  - In vitro, ex vivo, and in situ intestinal absorption characteristics of the
      antiviral ester prodrug adefovir dipivoxil.
AB  - Caco-2 monolayers (in vitro), rat intestinal sheets mounted in modified Ussing
      Chambers (ex vivo), and in situ intestinal perfusion of rat ileum were used as
      models to determine and compare the absorption characteristics of the antiviral
      agent 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA, adefovir) and its
      bis(pivaloyloxymethyl)-ester prodrug [bis(POM)-PMEA, adefovir dipivoxil].
      Although metabolism of adefovir dipivoxil was more pronounced in the ex vivo and
      in situ models than in the Caco-2 system, the transport of 'total adefovir' [=
      adefovir dipivoxil and its metabolites mono(POM)-PMEA and adefovir] was
      comparable in the three models. Compared with transport of the parent compound
      (adefovir), use of adefovir dipivoxil resulted in a significant increase in
      transport of total adefovir in the in vitro ( approximately 100-fold) and the in
      situ ( approximately 10-fold) models; in contrast, the ex vivo method failed to
      demonstrate a remarkable transport enhancement when using the ester prodrug.
      Similar to the results obtained in the Caco-2 model, the inclusion of the P
      glycoprotein inhibitor verapamil resulted in transport enhancement during in situ
      perfusion of rat ileum with adefovir dipivoxil; however, no effect of verapamil
      could be observed in the ex vivo model. The results of this study confirm the
      utility of both the in vitro and in situ models to assess intestinal transport
      and metabolism of adefovir dipivoxil. The ex vivo model appeared to be less
      appropriate because of its inability to discriminate transport following
      administration of adefovir or adefovir dipivoxil and because of the absence of an
      effect of verapamil on transport when using adefovir dipivoxil.

PMID- 10906730
TI  - The relationship between "BET" and "free volume"-derived parameters for water
      vapor absorption into amorphous solids.
AB  - Water vapor absorption isotherms for amorphous solids with the same chemical
      composition but differing in molecular weight (i.e., PVP-90, PVP-30, and PVP-12),
      and for glucose, trehalose, and two molecular weight grades of dextran were
      obtained at 30 degrees C and analyzed using the Brunauer-Emmett-Teller (BET)
      equation to obtain the parameters, W(m) and C(B). Similar analyses were carried
      out for the same molecule (e.g., glucose or fructose) at -10 and 40 degrees C.
      Within each chemical group, W(m), the apparent BET-like parameter that is
      generally referred to as the "monolayer-limit of absorption", changed very
      little. In contrast, C(B), a measure of the free energy of absorption,
      significantly increased with increasing molecular weight or decreasing
      temperature, leading to a shift from a Type III to a Type II isotherm. The shift
      in isotherm shape correlates directly with the glass transition temperature,
      T(g), of the dry sample relative to the operating temperature, T (i.e., Type III
      when T > T(g) and Type II when T < T(g). These results are shown to be consistent
      with the combined Flory-Huggins solution model and Vrentas structural relaxation
      model; wherein Type II isotherm behavior, observed for T < T(g), reflects
      nonideal volumetric contributions to the overall free energy of absorption due to
      plasticization by water, as described by Vrentas, whereas Type III behavior only
      reflects the Flory-Huggins solution model. These volumetric free energy changes
      within each chemical group are shown to be correlated to the values of the "BET"
      parameter C(B).

PMID- 10906731
TI  - Effect of short-, medium-, and long-chain fatty acid-based vehicles on the
      absolute oral bioavailability and intestinal lymphatic transport of halofantrine
      and assessment of mass balance in lymph-cannulated and non-cannulated rats.
AB  - The contribution of lymphatic transport and absorption directly into the portal
      blood to the overall oral bioavailability of a model lipophilic drug,
      halofantrine (Hf), was determined in lymph-cannulated, conscious, unrestrained
      rats after administration in lipidic vehicles with different fatty acid chain
      lengths. Both lymphatic transport (C(18)-based vehicle, 15.8% of dose > C(8-10),
      5. 5% > C(4), 2.22% > C(0), 0.34%) and total systemic exposure (C(18), 22.7% of
      dose > C(8-10), 19.2% > C(4), 15.2% > C(0), 6.4%) of Hf were enhanced by the
      presence of lipids in the formulation and specifically by an increase in the
      fatty acid chain length of the coadministered lipid. Increases in lymphatic drug
      transport appeared to correlate with increases in lymphatic lipid transport.
      Surprisingly, where lymphatic transport was the primary mechanism of drug
      transport to the systemic circulation (i.e., after administration in a C(18)
      based lipid vehicle), Hf bioavailability assessed in nonlymph-cannulated animals
      was lower than the extent of total availability measured in lymph-cannulated
      animals (estimated as percent appearing in the intestinal lymph plus percent
      transported directly into the blood), suggesting either presystemic drug
      clearance within the lymphatics or an altered systemic clearance pattern for
      lymphatically transported drug.

PMID- 10906732
TI  - Rapid-gradient HPLC method for measuring drug interactions with immobilized
      artificial membrane: comparison with other lipophilicity measures.
AB  - A fast-gradient high-performance liquid chromatographic (HPLC) method has been
      suggested to characterize the interactions of drugs with an immobilized
      artificial membrane (IAM). With a set of standards, the gradient retention times
      can be converted to Chromatographic Hydrophobicity Index values referring to IAM
      chromatography (CHI(IAM)) that approximates an acetonitrile concentration with
      which the equal distribution of compound can be achieved between the mobile phase
      and IAM. The CHI(IAM) values are more suitable for interlaboratory comparison and
      for high throughput screening of new molecular entities than the log k(IAM)
      values (isocratic retention factor on IAM). The fast-gradient method has been
      validated against the isocratic log k(IAM) values using the linear free energy
      relationship solvation equations based on the data from 48 compounds. The
      compound set was selected to provide a wide range and the least cross-correlation
      between the molecular descriptors in the solvation equation: (2) where SP is a
      solute property (e.g., logarithm of partition coefficients, reversed-phase (RP)
      HPLC retention parameters, such as log k, log k(w), etc.) and the explanatory
      variables are solute descriptors as follows: R(2) is an excess molar refraction
      that can be obtained from the measured refractive index of a compound, pi(2)(H)
      is the solute dipolarity/polarizability, summation operatoralpha(2)(H) and
      summation operatorbeta(2)(0) are the solute overall or effective hydrogen-bond
      acidity and basicity, respectively, and V(x) is the McGowan characteristic volume
      (in cm(3)/100 mol) that can be calculated for any solute simply from molecular
      structure using a table of atomic constants. It was found that the relative
      constants of the solvation equation were very similar for the CHI(IAM) and for
      the log k(IAM). The IAM lipophilicity scale was quite similar to the
      octanol/water lipophilicity scale for neutral compounds. The effect of charge on
      the interaction with IAM was studied by varying the mobile phase pH.

PMID- 10906733
TI  - Calcitonin and calcitonin gene-related peptide in the human prostate gland.
AB  - BACKGROUND: Calcitonin-related peptides have been found in the human prostate,
      and calcitonin (CT) and calcitonin gene-related peptide (CGRP) have been
      demonstrated in subpopulations of neuroendocrine (NE) cells. The purpose of this
      study was to determine the concentrations of CT and CGRP as well as the densities
      of NE cells in normal prostates, benign prostatic hyperplasia (BPH), and
      carcinoma of the prostate (CAP). METHODS: In 42 specimens of radical
      prostatectomy, the number of CT- and CGRP-immunoreactive NE cells in areas of
      normal and BPH tissue was determined, and compared with CAP tissue using
      immunocytochemistry. In addition, by radioimmunoassay (RIA), tissue levels of CT
      and CGRP were analyzed in extracts from areas of normal, BPH, and CAP tissue, as
      verified by adjacent histologic sections. RESULTS: A significant decrease in CT
      immunoreactive NE cells was observed in hyperplastic nodules of BPH in comparison
      to normal tissue. These findings were in parallel with a significant reduction in
      tissue CT level in BPH compared to normal tissue. There was also a marked, but
      statistically nonsignificant, reduction in CT levels in CAP tissue. In contrast,
      levels of CGRP in BPH and CAP tissue did not show any significant differences
      compared to normal tissue. CONCLUSIONS: CT and CGRP are present in NE cells of
      the human prostate. Calcitonin levels are significantly reduced in BPH, in
      parallel with a decreased number of CT-immunoreactive NE cells, whereas no
      significant changes in tissue levels of CGRP were observed. The functional
      significance of these findings is discussed.

PMID- 10906734
TI  - Efficacy and toxicity of radioimmunotherapy with (90)Y-DOTA-peptide-ChL6 for PC3
      tumored mice.
AB  - BACKGROUND: Radioimmunotherapy (RIT) is a new therapeutic modality capable of
      systemic delivery of radionuclides specifically to sites of metastatic cancer.
      The L6 monoclonal antibody has been shown to target prostate cancer in
      preclinical studies and, along with chimeric L6 (ChL6), has been used for RIT in
      breast cancer patients. METHODS: Pharmacokinetics, blood counts, body weight, and
      antitumor activity of RIT with (90)yttrium-((90)Y)-DOTA-peptide-ChL6 (75-260
      microCi) were determined in nude mice bearing human prostate cancer (PC3)
      xenografts. RESULTS: RIT produced durable, dose-dependent antitumor effects with
      a 100% response rate using 112 microCi and 150 microCi (the maximum tolerated
      dose) of (90)Y-DOTA-peptide-ChL6. Myelotoxicity was reversible, dose-limiting,
      and dose-related. RIT was associated with improved survival (P = 0.05). All 5
      mice in the 150-microCi group survived the 84-day study period vs. 1/8 (13%) for
      untreated, tumored control mice. CONCLUSIONS: (90)Y-DOTA-peptide-ChL6 targets PC3
      human prostate cancer xenografts in nude mice and has an antitumor effect. These
      results provide a basis for future RIT trials for patients with metastatic
      prostate cancer.

PMID- 10906735
TI  - Myosin heavy chain gene expression in normal and hyperplastic human prostate
      tissue.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) is common among aging men. Over
      80% of males 50-60 years and older have various degrees of bladder outlet
      obstruction secondary to BPH. Despite the tremendous medical impact of BPH, its
      molecular pathophysiology remains unclear. Current BPH research focuses on
      steroid hormonal effects, stromal-epithelial cell interaction, and oncogenes and
      growth factors. But little is known about the potential prostatic smooth muscle
      (SM) alterations that may occur during stromal hyperplasia. METHODS: To study SM
      phenotypic modulation in hyperplastic prostatic growth, we isolated and
      characterized the 3' end of human SM myosin heavy chain (SMMHC) cDNA as a
      molecular probe. Expression of SMMHC and nonmuscle myosin heavy chain (NMMHC) in
      human prostates was analyzed using Western blot, Northern blot, and in situ
      hybridization to determine if BPH tissue expresses significantly less SMMHC and
      more NMMHC than a normal prostate. In addition, a competitive, reverse
      transcription (RT) polymerase chain reaction (PCR) method was adapted to quantify
      SMMHC and NMMHC mRNA expression at the sensitivity level of 10(-21) mole per mg
      of wet tissue. RESULTS: Western blot, Northern blot, and in situ hybridization
      results reveal that both SMMHC and NMMHC are expressed in the human prostate,
      while SMMHC is the predominant form found in normal prostate stroma. Results from
      competitive RT-PCR analysis indicate that NMMHC mRNA expression is approximately
      10(-20) mole/mg of tissue. The SMMHC mRNA expressed is approximately 10(-18)
      mole/mg. No significant difference was found when NMMHC mRNA expression was
      compared between normal and BPH periurethral tissues. However, SMMHC expression
      was reduced almost fivefold in BPH compared to normal prostate, despite an
      increase in prostatic stromal mass. CONCLUSIONS: Our results suggest the
      pathogenesis of BPH is associated with a unique type of SM proliferation. Such
      proliferation is characterized by downregulation of SMMHC mRNA expression but
      without upregulation of NMMHC mRNA expression, the pattern seen in proliferating
      SM cells in culture and in other pathologic forms of SM hyperplasia (e.g.,
      atherosclerosis). These findings support a model of BPH typified by active smooth
      muscle proliferation early in the disease process, and supports clinical
      observations that suggest ongoing prostate growth of the prostate is minimal in
      older men. Therapeutic strategies to prevent disease progression should therefore
      focus on early phases of prostatic growth.

PMID- 10906736
TI  - Identification of the glycosaminoglycan keratan sulfate in the prostatic
      secretory cell.
AB  - BACKGROUND: Prostate secretory granules (PSG) represent the basic secretory unit
      of the prostate gland, containing many of its exocrine proteases. Recent analysis
      of intraluminal corpora amylacea, a proposed by-product of PSG secretion,
      detected sulfated glycosaminoglycans (GAG) possibly keratan sulfate (KS),
      indicating a secretory mechanism for GAG in the human prostate surface epithelial
      cell. METHODS: Immunostains using anti-KS and anti-prostate-specific antigen
      (PSA) were evaluated on 10 sequential radical prostatectomy specimens, three of
      which had received neoadjuvant antiandrogen therapy. Extracts of normal secretory
      tissue as well as a sample composed almost entirely of prostatic stroma were
      subjected to Western blot analysis, using the same antibody panel. RESULTS:
      Keratan sulfate secretion from the normal prostate epithelial cell has been
      confirmed and correlates, as does PSA, with the presence of cytoplasmic PSG. No
      such correlation exists in most adenocarcinomas or in benign epithelium after
      androgen ablation. Western blot analyses confirmed tissue immunostains and
      demonstrated a secretory proteoglycan of 70-95 kDa. CONCLUSIONS: Recognition of
      PSG heralds a novel secretory mechanism within the human prostate gland that is
      linked to the secretion of KS. The role of KS in normal prostate secretion
      remains unknown, although it appears downregulated in neoplastic and androgen
      ablated cells.

PMID- 10906737
TI  - Value of reverse transcription polymerase chain reaction assay in pathological
      stage T3N0 prostate cancer.
AB  - BACKGROUND: We tested the ability of the nested reverse transcription polymerase
      chain reaction (RT-PCR) assay to detect signs of biochemical recurrence of
      prostate cancer in the lymph nodes and peripheral blood of patients with pT3N0
      prostate cancer. METHODS: Using lymph nodes and pre- and postoperative peripheral
      blood dissected from 30 patients with pT3N0 prostate cancer treated by radical
      prostatectomy, we used RT-PCR for prostate-specific membrane antigen (PSM) and
      serum prostate-specific antigen (PSA) to determine the presence of prostate
      cancer. Results of the nested RT-PCR assay were compared with pathological stages
      and biochemical recurrence. RESULTS: Two of 13 patients with capsular penetration
      (15%), 6 of 10 patients with invasion of seminal vesicles (60%), and 3 of 7
      patients with a positive surgical margin (43%) were RT-PCR-positive for PSM
      and/or PSA in the lymph nodes. Results of preoperative RT-PCRs of peripheral
      blood for PSM and for PSA significantly differed between positive and negative
      results of RT-PCR in lymph nodes (P < 0.001 and P < 0.001, respectively). Results
      of postoperative RT-PCRs of peripheral blood for PSM and for PSA also
      significantly different between positive and negative results of RT-PCR in lymph
      nodes (P = 0.011 and P = 0.001, respectively). Nine of 11 patients with positive
      nested RT-PCR for PSM and/or PSA in the lymph nodes (82%) experienced biochemical
      recurrence. Significant difference in Kaplan-Meier recurrence-free actuarial
      curves was noted between patients who nested positive and negative on RT-PCR in
      the lymph nodes, pre- and postoperative peripheral blood, biopsy and
      prostatectomy Gleason score, and preoperative PSA values. In multivariate
      analysis, biopsy and prostatectomy Gleason score (P = 0.026, P = 0.020,
      respectively), pre- and postoperative RT-PCR for PSM in peripheral blood (P =
      0.030 and P = 0.040, respectively), and RT-PCR for PSM in lymph nodes (P = 0.035)
      were independent prognostic factors. CONCLUSIONS: Nested RT-PCR assay of the
      lymph nodes or peripheral blood significantly predicted biochemical recurrence
      after surgery. It may help identify patients at risk for recurrence and
      progression of prostate cancer.

PMID- 10906738
TI  - Endocrine patterns in patients with benign and malignant prostatic diseases.
AB  - BACKGROUND: The known importance of the endocrine system, particularly of steroid
      hormones, for development of the prostate gland and the fact that steroid
      hormones act as immunmodulators prompted us to compare hypophyseal, adrenal, and
      gonadal hormones, including cortisol, in patients with benign and malignant
      prostatic diseases. METHODS: Patients with newly diagnosed, untreated prostate
      cancer (PC) (n = 75) and, as a control population, those with untreated lower
      urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) (n = 159)
      entered this prospective study. In all patients, the following parameters were
      obtained by serum analysis: prostate-specific antigen (PSA), human luteinizing
      hormone (hLH), human follicle-stimulating hormone (hFSH), testosterone, estradiol
      (E2), cortisol, and dehydroepiandrosterone-sulphate (DHEA-S). Serum samples were
      collected of fasting patients between 7. 30-10.00 AM. RESULTS: Age was comparable
      in both groups (PC: 65.6 +/- 7.6 years (mean +/- standard deviation) vs.
      controls: 64.9 +/- 8. 1 years; P = 0.56). HFSH (PC: 6.6 +/- 3.9 mIU/ml; controls:
      8.4 +/- 6.4 mIU/ml; P = 0.04), hLH (PC: 5.3 +/- 4.8mIU/ml; controls: 7.6 +/- 6.2
      mIU/ml; P = 0.009), and estradiol (PC: 25.8 +/- 12.7 pg/ml; controls: 32.6 +/-
      12.6 pg/ml; P = 0.0003) were significantly lower in PC patients than controls.
      Cortisol (PC: 16.7 +/- 4.2 microg/dl; controls: 13.5 +/- 4.3 microg/dl; P <
      0.0001) was significantly higher in cases. The difference for cortisol and
      estradiol concentrations between PC patients and controls held true in all life
      decades. Serum concentrations for DHEA-S and testosterone were comparable between
      PC and control patients. In PC patients, none of the endocrine parameters
      correlated to serum PSA or clinical/pathological stage. CONCLUSIONS: Patients
      with newly diagnosed, untreated PC yielded significantly higher cortisol and
      lower estradiol serum concentrations than controls. The known effect of cortisol
      on the immune status warrants further studies.

PMID- 10906739
TI  - Sympathetic efferent pathways projecting to the prostate in the dog.
AB  - BACKGROUND: The laterality of the signals passing through the splanchnic nerves
      to each lobe of the prostate has not been studied. METHODS: Bilateral
      distribution of sympathetic signal to both lobes of the canine prostate was
      determined by measuring contraction of the prostate by stimulation of
      thoracolumbar splanchnic nerves with or without transection of unilateral
      hypogastric nerve (HGN). RESULTS: The 2nd-5th lumbar splanchnic nerve (LSN)
      stimulation elicited prostatic contraction. Twenty-five of 27 right LSN
      stimulations elicited contraction of the lobe, 21 bilaterally and 4 unilaterally.
      Twenty-three of 25 left LSN stimulations elicited contraction of the lobe, 22
      bilaterally and one unilaterally. The above stimulations did not elicit a
      dominant response in the lobe of the stimulated side. After transection of the
      right HGN, right and left LSN stimulation elicited contraction of the lobe
      bilaterally and did not induce dominant response in the lobe of the non-lesioned
      side. After transection of the left HGN, similar results were obtained.
      CONCLUSIONS: The results indicate that each of the LSNs sends signals to
      bilateral lobes via multiple routes with two crossing sites at the level of the
      caudal mesenteric plexus and prostate, and that the signals elicit contraction of
      the lobe without a dominant side.

PMID- 10906740
TI  - Partial sequencing and tissue distribution of the canine isoforms of steroid
      5alpha-reductase type I and type II.
AB  - BACKGROUND: The dog is regarded to be a valid model to test the effects of 5alpha
      reductase inhibitors on prostatic growth. However, limited information is
      available on the characteristics or even existence of 5alpha-reductase isozymes
      in this species. METHODS: Here, we set out to clone the cDNA of the dog isoforms
      of 5alpha-reductase type I and type II by a degenerate cloning strategy and to
      assess the tissue distribution of both transcripts and the enzymatic activity of
      the isozymes. RESULTS: We identified two clones with homology to the human 5alpha
      reductase isoforms type I and type II to be expressed in dog prostate. At the
      amino-acid level, these partial clones were found to exhibit a homology with
      their human counterparts of 83% and 88%, respectively. The expression levels of
      5alpha-reductase mRNA were screened by RT-PCR in a number of dog tissues. No
      correlation was found between tissue mRNA expression and enzymatic 5alpha
      reductase activities. CONCLUSIONS: The present study describes the partial
      cloning of the dog 5alpha-reductase isozymes and their tissue distribution. These
      results provide additional data for the use of the dog as an animal model to
      investigate the role of 5alpha-reductase isozymes in steroid metabolism.

PMID- 10906741
TI  - Central nervous system neurons labeled following the injection of pseudorabies
      virus into the rat prostate gland.
AB  - BACKGROUND: The human prostate gland plays an important role in male fertility
      and is involved in different functional pathologies of the male lower urinary
      tract (LUT). The role of the prostate in these medical disorders is mainly
      unknown. Traditional surgical therapeutic attempts often fail to help these
      patients. For years, the clinical sciences have been stagnating due to a lack of
      basic science knowledge. Investigations into neuroanatomy and neurophysiology are
      urgently needed. Therefore, the neuroanatomy of the prostate gland in an
      experimental setup was explored. Recent progress in neuroscience methodology
      allows a transneuronal tracing by using a self-amplifying virus tracer,
      pseudorabies virus (PRV). METHODS: Sixty-two individual adult male Sprague-Dawley
      rats were used for retrograde transneuronal mapping of the spinal cord and brain
      stem after PRV-injection and control experiments. A PRV-tracer (5 microl, 1 x
      10(8) pfu/ml) was injected into the prostate gland. After a survival time of 72,
      96, or 120 hr, the animals were sacrificed. Brain and spinal cord were harvested
      via a dorsal laminectomy. After cutting on a freezing microtome, the tissue was
      immunostained for PRV. RESULTS: PRV-positive cells were found within the sacral
      (S1-S2) and the thoracolumbar (T13-L2) spinal cord. At the supraspinal level,
      positive cells were found within the following regions: nucleus raphe, lateral
      reticular formation, nucleus gigantocellularis, A5 noradrenergic cell region,
      locus coeruleus, pontine micturition center, hypothalamus, medial preoptic
      region, and periaquaductal gray. CONCLUSIONS: This is the first investigation on
      the central innervation of the prostate gland showing a broad central
      representation of neurons involved in the control of the prostate gland. It is
      obvious, comparing data from the literature, that there is a broad overlap in the
      innervation of pelvic visceral organs (bladder, rectum, and urethra). The
      appreciation of these neuroanatomical circumstances allows a growing
      understanding of common urological pathologies within the pelvis (pelvic pain,
      lower urinary tract, and bowel dysfunction).

PMID- 10906743
TI  - Screening and early detection of prostate cancer.

PMID- 10906742
TI  - Different proportions of various prostate-specific antigen (PSA) and human
      kallikrein 2 (hK2) forms are present in noninduced and androgen-induced LNCaP
      cells.
AB  - BACKGROUND: Human prostate-specific antigen (PSA) and human kallikrein 2 (hK2)
      are expressed primarily by prostate epithelial cells. PSA and hK2 both exist as
      free protein and complexed with protease inhibitors (e.g., alpha1
      antichymotrypsin, ACT) in serum. The expression of PSA and hK2 in LNCaP cells is
      upregulated by androgen. METHODS: LNCaP, a prostate cancer cell line that
      secretes both PSA and hK2, was used as a model to study the biosynthesis and
      processing of PSA and hK2 upon androgen induction. RESULTS: Precursor (zymogen or
      pro) forms of both PSA and hK2 were detected in spent media of induced and
      noninduced LNCaP cells, indicating that PSA and hK2 are secreted as proPSA (pPSA)
      and prohK2 (phK2), respectively, and are converted to the mature forms
      extracellularly. A 3-fold higher ratio of mature to pPSA was detected in the
      spent media of mibolerone-induced LNCaP cells compared to noninduced cells. In
      addition to the inactive proform of PSA, more than half of the mature unclipped
      PSA present in the spent media did not complex with exogenously added ACT. Spent
      media of mibolerone-induced LNCaP cells contained nearly 100% mature hK2, whereas
      the spent media of noninduced cells contained mostly phK2. CONCLUSIONS: These
      results indicate that androgens not only upregulate the expression of these
      kallikreins, but also have a significant effect on the processing of PSA and hK2.
      These results also show that LNCaP cells express a heterogeneous mixture of
      inactive PSA and hK2 forms that may serve as a model for the genesis of these
      forms in physiological fluids. These findings may also provide insights into the
      forms and ratios of PSA and hK2 in normal and malignant breast tissues.

PMID- 10906744
TI  - Structure of the nervous system of Myzostoma cirriferum (Annelida) as revealed by
      immunohistochemistry and cLSM analyses.
AB  - The nervous systems of juvenile and adult Myzostoma cirriferum Leuckart, 1836,
      were stained with antisera against 5-HT (5-hydroxytryptamine, serotonin),
      FMRFamide, and acetylated alpha-tubulin in combination with the indirect
      fluorescence technique and analyzed by confocal laser scanning microscopy. The
      central nervous system consists of two small cerebral ganglia, connected by a
      dorsal commissure, a ventral nerve mass, and a pair of long circumesophageal
      connectives joining the former to the latter. The two neuropil cords within the
      ventral nerve mass curve outward and are joined to one another anteriorly and
      posteriorly. They are connected by 12 commissures, forming a ladder-like system.
      A single median nerve runs along the midventral axis. In addition to the
      circumesophageal connectives, 11 peripheral nerves arise from each main cord. The
      first innervates the anterior body region. The others form five groups of two
      nerves each, the first and thicker nerve of which is the parapodial nerve,
      innervating the parapodium and two corresponding cirri. Except for those in the
      most posterior group, the second nerves innervate the lateral organs and the body
      periphery. Serotonergic perikarya are arranged in six more or less distinct
      clusters, the first lying in front of and the other five between the main nerve
      cords. The distribution pattern of the FMRFamidergic perikarya is less clear and
      the somata lie between and outside the cords. One pair of dorsolateral
      longitudinal nerves was visualized by tubulin staining. Peripheral nerves and the
      commissures, in particular, demonstrate a segmental organization of the nervous
      system of M. cirriferum. Furthermore, their arrangement indicates that the body
      consists of six segments, the first of which is identifiable only by the first
      pair of peripheral nerves, the first two commissures, and the anteriormost
      ventral ganglion. The nervous system M. cirriferum thus exhibits several
      structures also found in the basic plan of the polychaete nervous system.

PMID- 10906745
TI  - Intraspecific differences in olfactory sensilla in relation to diet breadth in
      Uroleucon ambrosiae (Homoptera: Aphididae).
AB  - The olfactory plate organs found on the proximal segments of aphid antennae, the
      secondary rhinaria, were studied in apterae of the aphid Uroleucon ambrosiae. The
      numbers and shapes of these structures are important taxonomic characters in
      Aphididae, but they also show intraspecific variation within a morph. In this
      study, numbers were found to vary with aphid size but, independent of size, were
      greater in aphids collected in the eastern than in the southwestern United
      States. In addition, the sizes of rhinaria were greater in eastern than in
      southwestern aphids. These differences correlate with previously recorded
      differences in diet breadth and the efficiency of finding and settling on food:
      eastern aphids specialize on the host Ambrosia trifida, on which they settle
      relatively efficiently, while southwestern aphids are more generalized and less
      efficient. Greenhouse experiments demonstrated that differences in rhinaria are
      partly determined genetically. Southwestern aphids showed bilateral asymmetry in
      length of antennal segments though not in numbers of rhinaria, but only on
      certain adopted hosts that were apparently inferior for growth. The significance
      of these intraspecific differences is discussed in relation to the physiology,
      ecology, and evolution of host range.

PMID- 10906746
TI  - Ultrastructural observations on sperm storage in the ovary of the platyfish,
      Xiphophorus maculatus (Teleostei: poeciliidae): the role of the duct epithelium.
AB  - Sperm storage is an important phenomenon occurring in viviparous and oviparous
      teleosts and contributes to the reproductive life history of these forms. There
      is a paucity of morphological studies on sperm storage in fishes. The majority of
      these have been confined to the light level of investigation. In this report, we
      describe, at the ultrastructural level, sperm storage in the viviparous
      platyfish, Xiphophorus maculatus. Female platyfish, as is typical of the
      poeciliids, are capable of storing viable sperm for up to several months within
      the ovary and gonoduct. We observed that sperm stored within inseminated
      platyfish became associated with specific epithelial cells (SACs) lining the
      oviduct. Two forms of association were seen: 1) sperm were found within deep
      surface pits and pockets, and 2) the spermatozoa were taken up and incorporated
      within the cytoplasm of the SACs. Junctional complexes in the form of tight
      junctions (zona occludens) and desmosomes at the apico-lateral surfaces of the
      SACs were prevalent. The junctions could have contributed to allograft survival
      of the haploid heterogenetic sperm cells within the female's reproductive tract.
      Our results shed light on the mechanism of sperm storage in the platyfish and
      could serve as a model for other poeciliid species and teleosts that are capable
      of storing sperm.

PMID- 10906747
TI  - Examination of intrafascicular muscle fiber terminations: implications for
      tension delivery in series-fibered muscles.
AB  - Mammalian skeletal muscles with long fascicle lengths are predominantly composed
      of short muscle fibers that terminate midbelly with no direct connection to the
      muscle origin or insertion. The manner in which these short fibers terminate and
      transmit tension through the muscle to their tendons is poorly understood. We
      made an extensive morphological study of a series-fibered muscle, the guinea pig
      sternomastoid, in order to define the full range of structural specializations
      for tension transmission from short fibers within this muscle. Terminations were
      examined in single fibers, teased small bundles of fibers, and in sections at
      both the light and electron microscopic level. In many cases, sites of fiber
      termination were defined by reactivity for the enzyme acetylcholinesterase, which
      also marks myotendinous junctions. Additionally, transport of the lipophilic
      fluorescent dye, DiI, or injection of Lucifer Yellow were used to visualize
      undisturbed fiber terminations in whole muscles using confocal and fluorescence
      microscopy. At the light microscopic level, we find that intrafascicularly
      terminating fibers end about equally often in either a long progressive taper, or
      in a series of small or larger blunt steps. Combinations of these two
      morphologies are also seen. However, when analyzed at higher resolution with
      confocal or electron microscopy, the apparently smooth progressive tapers appear
      also to be predominantly composed of a series of fine stepped terminations.
      Stepwise terminations in most cases join face-to-face with complementary endings
      of neighboring muscle fibers, some via an extended collagenous bridge and others
      at close interdigitating myomyonal junctions. These muscle-to-muscle junctions
      show many of the features of myotendinous junctions, including dense
      subsarcolemmal plaques in regions of myofibrillar termination and we suggest that
      they serve to pass tension from fiber to fiber along the longitudinal axis of the
      muscle. In addition, we observe regions of apparent side-to-side adhesion between
      neighboring fibers at sites where there is no apparent fiber tapering or
      structural specialization typical of myofibril termination. These sites show
      acetylcholinesterase reactivity, and large numbers of collagen fibers passing
      laterally from fiber to fiber. These latter connections seem most likely to be
      involved in lateral transmission of tension, either from fiber to fiber, or from
      fiber to endomysium. Overall, our results suggest that tension from
      intrafascicularly terminating fibers is likely to be passed along the muscle to
      the tendon using both in-series and in-parallel arrangements. The results are
      discussed in light of current theories of tension delivery within the series
      fibered muscles typical of large, nonprimate mammals.

PMID- 10906749
TI  - Anatomical subdivisions of the stomach of the Bactrian camel (Camelus
      bactrianus).
AB  - Twenty stomachs of Bactrian camels (Camelus bactrianus) were studied by gross
      dissection. Based on the configuration of the stomach and the structure of the
      mucous membrane, the stomach was divided into three ventricles that differ from
      the arrangement described for ox and sheep. The first and second ventricles of
      the proventriculus of camel form one stomach rather than two different stomachs.
      These ventricles of the proventriculus do not correspond to the rumen and
      reticulum of ox and sheep. The third ventricle appears to be the abomasum. One
      part of the abomasum has reticular mucosal folds that indicate it is not the
      reticulum. A second part of the abomasum has longitudinal mucosal folds
      suggesting it is not the omasum. Three glandular sac areas associated with the
      preventriculus and abomasum are also described.

PMID- 10906748
TI  - Ultrastructure of the reproductive system of the black swamp snake (Seminatrix
      pygaea). II. Annual oviducal cycle.
AB  - This article is the first ultrastructural study on the annual oviducal cycle in a
      snake. The ultrastructure of the oviduct was studied in 21 females of the
      viviparous natricine snake Seminatrix pygaea. Specimens were collected and
      sacrificed in March, May, June, July, and October from one locale in South
      Carolina during 1998-1999. The sample included individuals: 1) in an inactive
      reproductive condition, 2) mated but prior to ovulation, and 3) from early and
      late periods of gravidity. The oviduct possesses four distinct regions from
      cranial to caudal: the anterior infundibulum, the posterior infundibulum
      containing sperm storage tubules (SSTs), the uterus, and the vagina. The
      epithelium is simple throughout the oviduct and invaginations of the lining form
      tubular glands in all regions except the anterior infundibulum and the posterior
      vagina. The tubular glands are not alveolar, as reported in some other snakes,
      and simply represent a continuation of the oviducal lining with no additional
      specializations. The anterior infundibulum and vagina show the least amount of
      variation in relation to season or reproductive condition. In these regions, the
      epithelium is irregular, varying from squamous to columnar, and cells with
      elongate cilia alternate with secretory cells. The secretory product of the
      infundibulum consists largely of lipids, whereas a glycoprotein predominates in
      the vagina; however, both products are found in these regions and elsewhere in
      the oviduct. In the SST area and the anterior vagina, tubular glands are compound
      as well as simple. The epithelium of the SST is most active after mating, and
      glycoprotein vacuoles and lipid droplets are equally abundant. When present,
      sperm form tangled masses in the oviducal lumen and glands of the SST area. The
      glands of the uterus are always simple. During sperm migration, a carrier matrix
      composed of sloughed epithelial cells, a glycoprotein colloid, lipids, and
      membranous structures surround sperm in the posterior uterus. During gravidity,
      tubular glands, cilia, and secretory products diminish with increasing
      development of the fetus, and numerous capillaries abut the basal lamina of the
      attenuated epithelial lining of the uterus.

PMID- 10906750
TI  - Morphology of the cloaca in the estuarine crocodile, Crocodylus porosus, and its
      plastic response to salinity.
AB  - The cloacal complex of Crocodylus porosus is composed of three chambers
      (proctodaeum, urodaeum, and coprodaeum) separated by tight, muscular sphincters.
      The proctodaeum is proximal to the cloacal vent and houses the genitalia. The
      urodaeum is the largest chamber, is capable of storing large quantities of urine,
      and is lined with an epithelium with the capacity for transepithelial water and
      ion exchange. The coprodaeum, the most orad cloacal chamber, is a small, only
      marginally expandable chamber that has an epithelium composed almost entirely of
      mucus-secreting cells. The coprodaeum and lower intestine are reported to be the
      site(s) for urine modification in birds and bladderless lizards. A radiographic
      trace of urine storage in C. porosus kept for 2 months under hyperosmotic
      conditions showed no signs of retrograde movement of urine into the coprodaeum or
      rectum. Instead, urine was stored in the urodaeum of C. porosus. Examination of
      the mucosal surface of the urodaeum by SEM showed a plastic response to
      environmental salinity, with a possible increase in surface area in animals kept
      in hyperosmotic water compared with animals from fresh water. We propose the
      urodaeum as the primary site for postrenal modification of urine in C. porosus.

PMID- 10906751
TI  - Analysis of the chicken DNA fragments that contain structural sites of attachment
      to the nuclear matrix: DNA-matrix interactions and replication.
AB  - Ten short DNA fragments have been selected from a library of the nuclear matrix
      attached DNA (nmDNA) from chicken erythrocytes by their ability to hybridize with
      the fraction of chicken replication origins isolated by nascent DNA strand
      extrusion. The primary structure of these fragments has been determined. Five of
      the sequences contained a topoisomerase II recognition site. Most of the studied
      DNA fragments also have a common eight-nucleotide motif, GCAGACCG/A. A sequence
      specific DNA-binding protein with a MW of 55 kDa that interacted with this motif
      has been identified. Some of the cloned DNA fragments promoted an increased level
      of transient plasmid replication in transfected chicken cells. The ability of
      plasmid bearing nmDNA fragments to replicate correlated directly with their
      ability to target plasmids to the nuclear matrix compartment.

PMID- 10906752
TI  - Expression of lactate dehydrogenases A and B during chicken spermatogenesis:
      characterization of testis specific transcripts.
AB  - The substrates required for glycolysis change markedly at successive stages of
      spermatogenesis suggesting a considerable plasticity in the expression of
      glycolytic enzymes. Lactate dehydrogenase (LDH) isoenzymes, LDH-A and LDH-B, are
      expressed in premeiotic, meiotic cells, and early spermatids, both in avian and
      mammalian spermatogenesis. Highly polyadenylated forms, particularly of LDH-A,
      were detected in chicken testis. While mammals and columbid birds express the
      testis specific LDH-C gene in meiotic and postmeiotic cells, several LDH-B testis
      specific transcripts were detected in the corresponding cells during chicken
      spermatogenesis. These testis specific transcripts and the mRNA of mammalian LDH
      C show several properties in common, such as temporal correlation of expression,
      mRNA stability, and repression of premature translation. These observations
      suggest that the testis specific transcripts could perform during chicken
      spermatogenesis the functions of the LDH-C mRNA in mammalian testis.

PMID- 10906753
TI  - Contortrostatin, a snake venom disintegrin, induces alphavbeta3-mediated tyrosine
      phosphorylation of CAS and FAK in tumor cells.
AB  - Contortrostatin is a homodimeric disintegrin that inhibits platelet aggregation
      and cell adhesion to extracellular matrix proteins by blocking integrins. The
      effect of contortrostatin on integrin-mediated signaling in tumor cells was
      investigated by studying tyrosine phosphorylation events and activation of
      specific signaling molecules. We found that at concentrations as low as 1 nM,
      soluble contortrostatin activates integrin signals leading to increased tyrosine
      phosphorylation of FAK and CAS, and that these signals are abolished by
      inhibiting Src family kinases. Using transfected 293 cells expressing specific
      integrins, it was determined that contortrostatin-generated signals are mediated
      exclusively by the alphavbeta3 integrin. This observation was extended by showing
      that cells lacking alphavbeta3, but expressing alphavbeta5 and alpha5beta1, do
      not respond in this way to contortrostatin treatment. In cells expressing
      alphavbeta3, blocking contortrostatin binding with antibodies against alphavbeta3
      completely abrogates contortrostatin signals. Monovalent disintegrins echistatin
      and flavoridin were incapable of affecting tyrosine phosphorylation alone, but
      when added simultaneously with contortrostatin, completely inhibited
      contortrostatin-initiated signals. We propose that the homodimeric nature of
      contortrostatin imparts the ability to crosslink alphavbeta3 integrins, causing
      Src activation and hyperphosphorylation of FAK and CAS. This activity may
      represent a novel mechanism by which tumor cell motility can be inhibited.

PMID- 10906754
TI  - Generation and initial characterization of conditionally immortalized chromaffin
      cells.
AB  - Adrenal chromaffin cells have been successfully used to attenuate chronic pain
      when transplanted near the spinal cord, but primary cells are neither homogeneous
      nor practical for routine use in human therapy. Conditional immortalization with
      the temperature-sensitive allele of the large T antigen (tsTag) and creation of
      stable chromaffin cell lines would advance our understanding of both the use and
      limits of cell lines that contain this immortalization gene for such therapies.
      Cultures of embryonic day 17 rat adrenal and neonatal bovine adrenal cells were
      immortalized with the temperature-sensitive allele of SV40 tsTag and chromaffin
      cell lines established. The rat chromaffin line, RAD5.2, and the bovine
      chromaffin cell line, BADA.20, both expressed immunoreactivities (ir) for all the
      catecholamine enzymes: tyrosine hydroxylase (TH), the first enzyme in the
      synthetic pathway for catecholamines, dopa-beta-hydroxylase (DbetaH), and
      phenylethanolamine-N-methyltransferase (PNMT). At permissive temperature (33
      degrees C), these chromaffin cells are proliferative, have a typical rounded
      chromaffinlike morphology, and contain detectable TH-, DbetaH-, and PNMT-ir. At
      nonpermissive temperature (39 degrees C), these cells stop proliferating,
      decrease Tag expression, and change the expression of TH-, DbetaH-, and PNMT-ir
      in vitro, suggesting increased differentiation at nonpermissive temperature. The
      chromaffin cell lines also express immunoreactivity for the opioid met-enkephalin
      (ENK) at permissive and nonpermissive temperatures. The expression of TH-ir in
      the bovine chromaffin cells is upregulated by the addition of dexamethasone (DEX)
      or forskolin during differentiation; TH-ir is not affected by the addition of DEX
      or forskolin in the rat chromaffin cells. The addition of forskolin during
      differentiation upregulates the expression of DbetaH-ir in the rat chromaffin
      cells. PNMT-ir is not affected by differentiation or agents in either cell line.
      However, catecholamine synthesis was not detectable by high-performance liquid
      chromatography, suggesting incomplete differentiation under current conditions,
      or influence by continued low levels of Tag expression. Both cell lines have been
      carried over many passages in vitro for more than 3 years and were repeatedly
      frozen and thawed. These data describe an initial step in the conditional
      immortalization of chromaffin cells that can maintain the phenotype of primary
      chromaffin cells in vitro over long periods. The use of such chromaffin cell
      lines that are able to deliver neuroactive molecules offers a novel approach to
      pain management.

PMID- 10906755
TI  - Expression of steroidogenic enzyme messenger ribonucleic acid and cortisol
      production in adrenocortical cells isolated from halothane-sensitive and
      halothane-resistant pigs.
AB  - Stress susceptibility in pigs is inherited by a single recessive gene (Hal(n)),
      and homozygous individuals can be identified by exposure to halothane anesthesia.
      Previous studies have shown that in stress-susceptible pigs, exposure to a high
      ambient temperature resulted in a twofold increase in corticotropin (ACTH) and
      lower plasma cortisol. To determine whether there is a fundamental difference in
      adrenocortical function between halothane-sensitive (HAL-S) and halothane
      resistant (HAL-R) pigs, independent of other factors influencing the hypothalamic
      pituitary-adrenal (HPA) axis, we compared cortisol responses to ACTH and 8-bromo
      cyclic AMP (8-Br-cAMP) in HAL-S and HAL-R pig adrenocortical cells in vitro. We
      also determined directly the accumulation of four different mRNAs encoding
      cholesterol side-chain cleavage cytochrome P450 (P450(scc)), 17alpha-hydroxylase
      cytochrome P450 (P450(17alpha)), 21-hydroxylase cytochrome P450 (P450(c21)) and
      11beta-hydroxylase cytochrome P450 (P450(11beta)) in HAL-S pig adrenal cells and
      compared them to HAL-R pigs. A time- and dose-dependent increase in medium
      content of cortisol and cAMP was observed after ACTH treatment. 8-Br-cAMP also
      caused a time- and dose-dependent increase in cortisol production in the medium.
      Addition of ACTH or 8-Br-cAMP to HAL-S and HAL-R male Lanyu small-ear miniature
      pig adrenocortical cells increased cortisol production in a dose- and time
      related manner. However, cells isolated from HAL-S pigs had a lower cortisol
      production in response to ACTH or 8-Br-cAMP compared to those from HAL-R pigs.
      Treatment of cultured cells with 8-Br-cAMP (0.5 mM) for 18 h resulted in a
      significant increase in P450(scc), P450(17alpha), P450(c21), and P450(11beta)
      mRNA levels. In the absence of 8-Br-cAMP, the four genes were expressed
      constitutively in both HAL-S and HAL-R pig adrenal cells. Densitometric scanning
      of the autoradiograph indicated that the relative amounts of P450(scc) and
      P450(17(alpha)) mRNAs in HAL-S pig adrenal cells were between 48% and 53% of
      those detected in HAL-R pig adrenal cells (P < 0.05). No difference in the
      amounts of P450(c21) and P450(11beta) was seen in HAL-S and HAL-R pig adrenal
      cells. Addition of 8-Br-cAMP (0.5 mM) resulted in a uniform increase in the
      levels of all four P450 mRNAs in both HAL-S and HAL-R pig adrenal cells. However,
      the amounts of P450(scc) mRNA in HAL-S pig adrenal cells were 67% (P < 0.05) of
      those measured in HAL-R pig adrenal cells, whereas the amounts of P450(17alpha ),
      P450(c21), and P450(11beta) mRNAs were similar in these cells. Our data suggest
      an HPA axis defect in HAL-S pigs at the adrenal level. This defect appears to be
      at the level of P450scc gene expression, which could be partially related to
      reduced cortisol production by ACTH stimulation.

PMID- 10906756
TI  - Overexpression of nPKC theta is permissive for myogenic differentiation.
AB  - Although protein kinase C (PKC) has been shown to participate in skeletal
      myogenic differentiation, the functions of individual isoforms of PKC in
      myogenesis have not been completely elucidated. These studies focused on the role
      of nPKC straight theta, an isoform of the PKC family whose expression has been
      shown to be regulated by commitment to the myogenic lineage, myogenic
      differentiation and innervation. We used the myogenic cell line C(2)C(12) as a
      tissue culture model system to explore the role of nPKC straight theta in the
      formation of multinucleated myotubes. We examined endogenous levels of nPKC
      straight theta in C(2)C(12) cells and showed that it is expressed at low levels
      in myoblasts compared to mouse skeletal muscle and that expression is maintained
      in myotubes. We overexpressed nPKC straight theta in C(2)C(12) myoblasts and
      examined the ability of overexpressing cells to differentiate into myotubes.
      Using an nPKC straight theta - green fluorescent protein (GFP) chimera to detect
      transfected myoblasts, we showed that overexpressed nPKC straight theta-GFP
      translocates to the plasma membrane in response to phorbol ester treatment of
      myoblast cultures in situ. nPKC straight theta-GFP was found to be completely
      extracted into the detergent-soluble fraction of cell lysates and was stably
      expressed throughout the extent of differentiation into myotubes. No difference
      was seen in the ability of myoblasts either overexpressing nPKC straight theta -
      GFP or GFP alone to form myotubes. These studies demonstrate that overexpression
      of nPKC straight theta does not interfere with fusion of myoblasts into myotubes
      suggesting that nPKC straight theta activity is not inhibitory for myogenesis.
      These studies also demonstrate a method for transfecting myoblasts and
      identifying differentiated cells that overexpress nPKC straight theta-GFP for
      investigating the function of nPKC straight theta in living myotubes.

PMID- 10906757
TI  - BMP-2 induces the expression of activin betaA and follistatin in vitro.
AB  - Activins are members of the transforming growth factor beta (TGF-beta)
      superfamily and have been shown to be multifunctional regulators of development
      and cell differentiation. Increasing evidence suggests activin betaA is involved
      in skeletal development. Using differential display PCR we have identified
      activin betaA as a gene associated with recombinant human bone morphogenetic
      protein-2 (rhBMP-2) induced differentiation of a mouse limb bud cell line,
      MLB13MYC clone 17, from a prechondroblastic to an osteoblastic phenotype. The
      expression of activin betaA peaks at 24 h of rhBMP-2 treatment, before detection
      of osteocalcin mRNA expression. Cycloheximide treatment inhibits induction of
      activin betaA, indicating a requirement for new protein synthesis. The induction
      of the mRNA encoding follistatin, an activin binding protein, was also examined.
      Follistatin mRNA increases within 18 h of rhBMP-2 treatment, as activin betaA
      mRNA increases but before it peaks. Treatment of MLB13MYC clone 17 cells with
      purified activin betaA concomitant with rhBMP-2 does not affect markers of
      chondrocyte or osteoblast differentiation, nor does treatment with purified
      activin betaA alone. This suggests that activin betaA exerts its effect via a
      paracrine mechanism. In situ hybridization analysis demonstrates that activin
      betaA expression is localized to cells in the developing interphalangeal joints
      of embryonic mouse limbs. This is consistent with in vivo induction by BMP-2
      which is also expressed in the developing joints. Activin betaA, therefore, is
      downstream from BMP-2 in the cascade of events that result in skeletal
      development.

PMID- 10906758
TI  - Type I collagen influences cartilage calcification: an immunoblocking study in
      differentiating chick limb-bud mesenchymal cell cultures.
AB  - Chick limb-bud mesenchymal cells, plated in high-density micro-mass culture,
      differentiate and form a matrix resembling chick epiphyseal cartilage. In the
      presence of 4 mM inorganic phosphate or 2.5 mM beta-glycerophosphate mineral
      deposits upon this matrix forming a mineralized tissue that, based on electron
      microscopy, x-ray diffraction and Fourier Transform Infrared microspectoscopy, is
      like that of chick calcified cartilage. In this culture system the initial
      mineral deposits are found on the periphery of the chondrocyte nodules. During
      differentiation of the cells in the high-density micro-mass cultures there is a
      switch from expression of type I collagen to type II, and then to type X
      collagen. However, type I collagen persists in the matrix. Because there is some
      debate about whether type I collagen influences cartilage calcification, an
      immunoblocking technique was used to determine the importance of type I collagen
      on the mineralization process in this system. Studies using nonspecific goat anti
      chick IgG demonstrated that 1-100 ng/ml antibody added with the media after the
      cartilage nodules had developed (day 7) had no effect on the accumulation of
      mineral in the cultures. Nonspecific antibody added before day 7 blocked
      development of the cultures. Parallel solution based cell-free studies showed
      that IgG did not have a strong affinity for apatite crystals, and had no
      significant effect on apatite crystal growth. Type I collagen antibodies (1-200
      ng/ml) added to cultures one time on day 9 (before mineralization started), or on
      day 11 (at the start of mineralization), slightly inhibited the accumulation of
      mineral. There was a statistically significant decrease in mineral accretion with
      100 or 200 ng/ml collagen antibody addition continuously after these times. Fab'
      fragments of nonspecific and type I collagen antibodies had effects parallel to
      those of the intact antibodies, indicating that the decreased mineralization was
      not attributable to the presence of the larger, bulkier antibodies. The altered
      accumulation of mineral was not associated with cell death in the presence of
      antibody (demonstrated by fluorescent labeling of DNA) or with increased
      apoptosis (TUNEL-stain). In the immunoblocked cultures, EM analysis demonstrated
      that mineral continued to deposit on collagen fibrils, but there appeared to be
      fewer deposits. The data demonstrate that type I collagen is important for the
      mineralization of these cultures.

PMID- 10906759
TI  - Leukemia-associated AML1/ETO (8;21) chromosomal translocation protein increases
      the cellular representation of PML bodies.
AB  - Promyelocytic leukemia (PML) nuclear bodies are important components of nuclear
      architecture that are functionally linked to aberrant gene expression and
      disease. To understand the mechanisms that modify subnuclear distribution and
      regulatory activities of PML domains in leukemia, we performed immunofluorescence
      microscopy with a panel of normal diploid cells and established cell lines. We
      analyzed the representation and intranuclear distribution of PML domains. We find
      that multiple biological parameters contribute to heterogeneity in the subnuclear
      organization of PML domains in a broad spectrum of cell types. The subnuclear
      organization of PML domains was also evaluated following transient transfection
      with a series of vectors expressing normal hematopoietic and leukemia-related
      transcription factors. Our results show that expression of a chimeric
      transcription factor encoded by the tumor related chromosomal translocation
      (8;21) involving the AML1 and ETO loci is sufficient to cause reorganization of
      PML domains. This finding increases our understanding of the mechanisms by which
      the AML1/ETO protein may contribute to modified gene expression linked to the
      onset and progression of t(8;21) related acute myelogenous leukemia.

PMID- 10906761
TI  - Association of protein phosphatase 2A with its substrate vimentin intermediate
      filaments in 9L rat brain tumor cells.
AB  - The importance of protein phosphatases in maintaining the integrity of
      intermediate filaments is supported by the fact that intermediate filaments would
      undergo a massive reorganization in cells treated with inhibitors of protein
      phosphatases 1 and 2A. Herein we used okadaic acid to investigate the
      differential roles of protein phosphatases 1 and 2A in the maintenance of
      intermediate filament integrity in 9L rat brain tumor cells. Protein phosphatase
      2A activity was substantially inhibited after treatment with 400 nM okadaic acid
      for 2 h, whereas the activity of protein phosphatase 1 was only slightly
      affected. Furthermore, protein phosphatase 2A shows selective specificity toward
      phosphovimentin, which was immunologically precipitated from isotopically labeled
      and okadaic acid-treated cells. Further biochemical fractionation and microscopic
      studies revealed that vimentin intermediate filaments were colocalized with
      protein phosphatase 2A, but not protein phosphatase 1, in control cells. On
      okadaic acid treatment, vimentin filament disassembled and protein phosphatase 2A
      redistributed throughout the cytoplasm, suggesting that these two proteins
      separate from each other, whereas protein phosphatase 2A was inhibited. This
      working hypothesis was further supported by treatment with a low concentration
      (40 nM) of okadaic acid, which causes the same phenomenon. Taken together, our
      results showed that protein phosphatase 2A could be assigned to the intermediate
      filaments to serve the physiological role in maintaining the proper
      phosphorylation level of intermediate filaments in normal cells. This finding
      should pave the way for the elucidation of the regulatory mechanism of
      intermediate filament organization governed by protein phosphorylation.

PMID- 10906760
TI  - Characterization of the protein phosphatase 1 catalytic subunit in endothelium:
      involvement in contractile responses.
AB  - We have previously demonstrated the direct involvement of a type 1 Ser/Thr
      phosphatase (PPase 1) in endothelial cell (EC) barrier regulation [Am. J.
      Physiol. 269:L99-L108, 1995]. To further extend this observation, we
      microinjected either the Ser/Thr PPase inhibitor, calyculin, or the PPase 1
      inhibitory protein, I-2 into bovine pulmonary artery EC and demonstrated both an
      increase in F-actin stress fibers and a shift from a regular polygonal shape to a
      spindle shape with gaps apparent at the cell borders. Northern blot analysis with
      specific cDNA probes revealed the presence of three major PPase 1 catalytic
      subunit (CS1) isoforms (alpha, delta, and gamma) in human and bovine EC. To
      characterize the myosin-associated EC CS1 isoform, myosin-enriched bovine EC
      fraction was screened with anti-CS1alpha and anti-CS1delta antibodies The anti
      CS1delta antiserum, but not anti-CS1alpha antiserum cross reacts with the CS1
      isoform present in myosin-enriched fraction and CS1delta was found in stable
      association with EC myosin/myosin light chain kinase (MLCK) complex in MLCK
      immunoprecipitates under nondenaturing conditions. Consistent with these data,
      overexpression of CS1delta-GFP construct in bovine endothelium followed by
      immunoprecipitation of CS1 with anti-GFP antibody revealed the stable association
      of CS1delta with actomyosin complex. Finally, screening of a human EC oligo(dT)
      primed cDNA library with a probe encoding a rat CS1delta cDNA segment yielding
      several positive clones that encoded the entire CS1delta open reading frame and
      partially noncoding regions. Sequence analysis determined a high homology (
      approximately 99%) with human CS1delta derived from a teratocarcinoma cell line.
      Together, these data suggest that CS1delta is the major of PPase 1 isoform
      specifically associated with EC actomyosin complex and which participates in EC
      barrier regulation.

PMID- 10906762
TI  - Mediation of cell-substratum adhesion by RasG in Dictyostelium.
AB  - Previous studies on the functions of the RasG gene in the cellular slime mold,
      Dictyostelium discoideum, have revealed that it is required for normal motility
      and cytokinesis. To further understand how the RasG gene regulates various
      cellular processes, we transformed an activated form of RasG, that is, RasG
      (G12T), a mutation from glycine to threonine at amino acid position 12 into wild
      type KAX-3 cells. This produced moderate but constitutive RasG(G12T) protein
      expression, which causes cells to become significantly more adherent to the
      substratum than are wild type cells. The RasG(G12T) transformants also grow
      slowly on bacterial plates, and engulf fewer bacteria on filter surfaces,
      indicating a defect in phagocytosis when cells are adhered. The expression of the
      activated RasG also dramatically reduces the number of filopodia on the cell
      surface. Tyrosine phosphorylation on a 43 kDa protein (most likely actin) of the
      RasG (G12T) transformants is highly elevated. Taken together, our observations
      suggest that RasG is crucial for Dictyostelium cell-substratum adhesion during
      growth and that RasG may play a role in adhesion-mediated phagocytosis. Our
      results also suggest that RasG is important in filopodial formation and that RasG
      is involved in the signal pathway that is regulated by tyrosine phosphorylation.

PMID- 10906764
TI  - Identification of the increased expression of monocyte chemoattractant protein-1,
      cathepsin S, UPIX-1, and other genes in dystrophin-deficient mouse muscles by
      suppression subtractive hybridization.
AB  - The lack of dystrophin results in muscular dystrophy characterized by
      degeneration, inflammation, and partial regeneration of skeletal muscles. The
      fate of these muscles may be determined by the extent of adaptation to the defect
      and the efficiency of regeneration that is affected by inflammatory cells. We
      have used suppression subtractive hybridization and quantitative Northern blot
      analysis to identify differentially expressed genes. Increased expression of
      murine monocyte chemoattractant protein-1 (JE/MCP-1), cathepsin S, UPIX-1, nmb,
      cathepsin B, and lysozyme M mRNAs were identified in 2-month-old mdx mouse leg
      muscles. UPIX-1 is a novel gene. Although it was not expressed in control
      muscles, it was expressed in control brain, heart, and spleen. JE/MCP-1 and
      cathepsin S proteins in mdx muscles, as well as JE/MCP-1 protein in the serum of
      mdx mice were also detected. JE/MCP-1 may be responsible for attraction of
      inflammatory cells, and cathepsin S, a potent elastolytic protease, may
      contribute to the remodeling of the extracellular matrix that is required for the
      migration of these cells to the injured muscles.

PMID- 10906763
TI  - Expression and production of stathmin in growth plate chondrocytes is cell
      maturation dependent.
AB  - Growth plate cartilage is comprised of linear columns of chondrocytes with the
      least differentiated cells at one end and the terminally differentiated cells at
      the other end. Rat costochondral chondrocytes can be divided into the resting
      cell zone (reserve cell zone), which contains relatively immature chondrocytes
      (RC cells), and the phenotypically more mature prehypertrophic and upper
      hypertrophic cell zones, which together may be termed the growth zone
      chondrocytes (GC cells). When grown separately in monolayer culture, they
      continue to express their zone-specific phenotype, providing a model for
      assessing cell-maturation-dependent expression of molecules associated with
      differentiation. Stathmin (also called prosolin, Op18, p19, 19K, and others) is a
      highly conserved, phosphorylated cytosolic protein with apparent ubiquitous
      expression. Although its exact function is unknown, stathmin is considered to be
      a messenger phosphorylated protein, it plays a role in tubulin stability, and it
      may participate in both general and specific regulatory pathways. One uniform
      observation is that the expression of stathmin protein decreases in all cells as
      they become more terminally differentiated in culture. There have been no
      published data regarding stathmin expression and production in chondrocytes. This
      study was based on the hypothesis that stathmin exists in chondrocytes and that
      the mRNA and protein levels decline in the GC cell with respect to the RC cell.
      Stathmin mRNA levels were determined and quantitated by reverse transcription
      polymerase chain reaction (RT-PCR) and northern blots. Protein levels were
      determined using immunoblots. It was found that stathmin exists in chondrocytes
      and that RC cells express approximately twice the level of mRNA and protein to
      that found in GC cells. The results support the hypothesis and suggest that the
      level of stathmin expression and production in culture is related to the level of
      differentiation of RC and GC cells in vivo.

PMID- 10906765
TI  - Detection of mycobacterial DNA in papulonecrotic tuberculid lesions by polymerase
      chain reaction.
AB  - Tuberculids are a heterogeneous group of cutaneous lesions. Recent discoveries of
      M. Tuberculosis DNA in these lesions by PCR suggest that M. tuberculosis could
      play a role in their pathogenesis. The aim of this study was to demonstrate the
      presence of M. tuberculosis DNA by polymerase chain reaction in papulonecrotic
      tuberculid lesions. Skin biopsy specimens from ten patients with papulonecrotic
      tuberculid lesions (histopathologic features) were studied. All of them tested
      solidly positive in a tuberculin intradermal test. A gene-amplification PCR,
      using primers capable of amplifying DNA in the M. tuberculosis complex, was
      performed to detect M. tuberculosis DNA in the lesions. A 285-bp sequence
      specific of M. tuberculosis complex was amplified and confirmed by Southern-blot
      hybridation with a 32 p 5'-labelled internal probe. No inhibitors were detected
      in the negative PCR samples. The PCR technique makes the detection of
      mycobacterial DNA in tuberculids a possibility, and therefore provides a rational
      basis for antituberculous therapy and for the clinical management of these
      disorders.

PMID- 10906766
TI  - Argatroban as an anticoagulant for both hematologic and chemical tests.
AB  - Argatroban possesses strong antithrombin-like activity. We evaluated the
      usefulness of argatroban in anticoagulating specimens for routine laboratory
      tests. Results using blood anticoagulated with argatroban corresponded well with
      the results of blood treated with ethylendiamine tetra-acetic acid (EDTA) in the
      complete blood count (CBC), including the WBC differential count and morphology
      of blood cells, when the CBC was performed within 2 hr of blood collection.
      Clinical chemistry results from argatroban-treated samples were similar to
      results obtained with serum specimens. Thus, argatroban may be a useful
      anticoagulant for emergency laboratory medicine.

PMID- 10906767
TI  - Functions of the Fc receptors for immunoglobulin G.

PMID- 10906768
TI  - Isolation of polioviruses and other enteroviruses in south Greece between 1994
      and 1998.
AB  - During the five-year period between 1994 and 1998, a total of 217 clinical
      samples were assessed for the isolation of enteroviruses at the Enterovirus
      Reference Centre for South Greece. Fourteen enterovirus strains belonging to
      different serotypes were isolated. These field strains were detected by cell
      culture in appropriate cell lines. They were subsequently identified by
      neutralizing antibodies with the LBM (Lim-Benyesh Melnick) mixed antisera pools
      up to 1995 and RIVM (National Institute of Public Health and the Environment,
      Bilthoven, The Netherlands) pools from 1996 onwards. The isolated viruses
      included two strains of poliovirus type 2 Sabin-like, three strains of poliovirus
      type 1 non-Sabin-like, one Coxsackie B2 (CBV2) strain, one Coxsackie B5 (CBV5)
      strain, one Echo 5 (ECV5) strain, one Echo 7 (ECV7) strain, three Coxsackie A16
      (CAV16) strains, and two currently enteroviral strains unidentified by RIVM
      pools. Reverse transcription-polymerase chain reaction (RT-PCR) using poliovirus
      specific primers or poliovirus type-specific primers and enterovirus specific
      primers from the highly conserved 5'-UTR, the latter followed by RFLP, was also
      applied in 6 clinical isolates (3 strains of poliovirus type 1 non-Sabin-like, 1
      polio type 2 Sabin-like, and 2 non-identified by RIVM pools enteroviruses). The
      advantages and the drawbacks of these assays against the conventional ones are
      discussed here. The isolations and the subsequent identification of the strains
      were carried out from fecal samples of clinical cases that included hand-foot-and
      mouth disease, meningitis, and acute flaccid paralysis. The reappearance of non
      Sabin-like poliovirus strains in Greece in 1996 after 14 years is considered to
      have an important medical and clinical value.

PMID- 10906769
TI  - Performance evaluation of a new chemiluminescent assay for prostate specific
      antigen.
AB  - Prostate specific antigen (PSA) is a glycoprotein found in the epithelial cells
      of the prostatic duct and acini. PSA is elevated in all four stages of prostate
      cancer as well as in benign prostatic hypertrophy. We evaluated a new
      chemiluminescent assay for PSA by comparing this assay with the microparticle
      enzyme immunoassay for PSA (MEIA) on the AxSYM analyzer (Abbott Laboratories,
      Abbott Park, IL) and a Hybritech Tandem R assay for PSA. The new chemiluminescent
      assay is recently available from Bayer Diagnostics (Tarrytown, NY) and can be run
      using the ACS: 180 Plus analyzer. Precision of the new chemiluminescent assay was
      evaluated using commercially available controls (Bayer Diagnostics). The within
      run and total CVs were 6.4 and 8.7% for the low control (mean: 0.43 microg/L),
      1.6 and 5.2% for the next level control (mean:1.94 mg/L), 4.3 and 4.9% for the
      medium control (mean: 2.10 mg/L), 1.2 and 3.9% for the high control 1 (mean:
      11.52 mg/L), and finally 3.2 and 6.9% for the high control 2 (mean: 21.52 mg/L).
      The spike recovery varied from 94.2 to 109.6% for five different specimens we
      studied. We also observed excellent dilution recoveries. For example, in the
      specimen supplemented with 3.02 mg/L of PSA, the dilution recoveries were 102. 1,
      104.7, and 103.7% for 1:2, 1:4, and 1:8 dilutions, respectively. We analyzed 113
      serum specimens from patients with various concentrations of PSA (range 0.5 mg/L
      2040 mg/L) using the new chemiluminescent assay and compared our results with the
      MEIA and Hybridtech (Tandem-R PSA) assays. Using x axis as the PSA concentrations
      obtained by the Tandem-R assay and the y axis as the PSA values obtained by the
      new chemiluminescent assay, we observed the following regression equations: y =
      1.04 x -0.19 (r = 0.99, n = 112). One specimen with PSA concentrations of 2040
      microg/L by the MEIA and 2156 microg/L by the chemiluminescent assay was not used
      for regression analysis. Similarly using x axis as the PSA concentrations
      obtained by the MEIA assay and y axis as the PSA concentrations obtained by the
      chemiluminescent assay, we observed the following regression equation: y = 0.88 +
      0.02 (r = 0.99, n = 112). We conclude that the new chemiluminescent assay has
      excellent precision and the results compared well with the existing assays.

PMID- 10906770
TI  - Preparations of recombinant HIV-1 p66 antigen to improve the specificity of
      immune complex transfer enzyme immunoassay of antibody IgG to HIV-1 reverse
      transcriptase.
AB  - Recombinant HIV-1 p66 (rp66, a subunit of reverse transcriptase (RT), a
      heterodimer of p66 and p51) was produced in Escherichia coli in three different
      ways. First, rp66 was produced as a part of the fusion protein of lacZ protein
      and HIV-1 pol protein consisting of three components: protease (p10), RT
      (p51/p66), and integrase (p31), and was released from the fusion protein by the
      protease (pol-rp66). Second, rp66 with Ser-Ser at the N-terminus was produced as
      a fusion protein with maltose-binding protein containing a factor Xa site between
      the two proteins (MBP-Ser-Ser-rp66) and was released from the fusion protein by
      factor Xa (Ser-Ser-rp66). Third, rp66 with Met-Gly at the N-terminus was produced
      in transformed cells (Met-Gly-rp66). The recombinant proteins were purified from
      sonic extracts of transformed cells by ammonium sulfate fractionation and various
      column chromatographies. MBP-Ser-Ser-rp66 and Met-Gly-rp66 were readily purified
      in sufficient amounts for labeling with 2, 4-dinitrophenyl groups and beta-D
      galactosidase from E. coli, but pol-rp66 and Ser-Ser-rp66 were not for enzyme
      labeling. Ser-Ser-rp66 was not only polymerized but also degraded to considerable
      extents. The purified preparations were labeled with 2,4-dinitrophenyl groups and
      beta-D-galactosidase and were tested in immune complex transfer enzyme
      immunoassay of antibody IgG to HIV-1 RT using serum samples from 600 HIV-1
      seronegative and 30 HIV-1 seropositive subjects. Among various combined uses of
      the two labeled preparations, the uses of 2,4-dinitrophenylated MBP-Ser-Ser-rp66
      and pol-rp66 with beta-D-galactosidase-labeled Met-Gly-rp66 showed the highest
      (99.8%) and the second highest (99.5%) specificities, which were higher than that
      with the labeled preparations used in the previous study (98. 0%).

PMID- 10906771
TI  - Synthetic polymer sulphonated polyisoprene as a universal anticoagulant for
      laboratory testing.
AB  - To evaluate the feasibility of a synthetic polymer, sulphonated polyisoprene
      (SPIP), to be used as a new laboratory anticoagulant, hematological items were
      compared between blood samples anticoagulated with EDTA and SPIP, as were
      biochemical and electrolyte items between serum samples and SPIP-anticoagulated
      blood. Among hematological items, the average platelet count of the SPIP group
      was significantly lower than that of the EDTA group, due to platelet aggregation
      in the SPIP group. Addition of kanamycin to SPIP, but not of aspirin or
      prostaglandin E1, restored platelet count to about 80% of that in the EDTA group,
      and increased coefficients of correlation with the EDTA group for most
      hematological items examined. For biochemical and electrolyte items, high (>
      0.95) correlation coefficients were obtained for 15 of 18 items between the serum
      and SPIP-anticoagulated samples. However, for some of these items, the addition
      of kanamycin decreased coefficients of correlation. Thus, SPIPs are excellent
      candidates for new anticoagulants that can be used for evaluation of
      hematological, biochemical, and electrolyte items with a single test tube in
      routine laboratory work. However, some improvements are required for use of
      kanamycin as an additive to inhibit platelet aggregation induced by SPIP, and in
      maintaining reliability of biochemical and electrolyte measurements.

PMID- 10906772
TI  - New method for quantifying anti-HIV1-gp160 antibodies in saliva, cervicovaginal
      secretions, and serum of infected women.
AB  - Antibody titers or units as measured by ELISA or similar assays represent only a
      semi-quantitative measurement of the antibody concentration. In the present
      study, a truly quantitative assay for evaluating antibody concentrations was
      developed. In the new assay, IgG and IgA antibody concentrations are expressed in
      absolute gravimetric units (weight/ml) rather than by more ambiguous terms such
      as titers or units. The procedure is based on the comparison of known
      concentrations of IgG or IgA bound to anti-F(ab)'(2) with the binding of an
      unknown concentration of antibodies to a specific antigen. We applied the new
      assay to the measurement of HIV1-gp160 specific IgG and IgA concentrations in
      cervicovaginal secretions (CVS), saliva, and sera of infected women. Measurement
      of antibody activity was obtained by comparing the amount of specific antibodies
      to the amount of total immunoglobulins found in the same compartment. Because of
      its quantitative and comparative nature, the assay was named comparative antibody
      gravimetric evaluation assay (CAGE).

PMID- 10906773
TI  - One-step heminested PCR for amplification of Neisseria meningitidis DNA in
      cerebrospinal fluid.
AB  - A one-step polymerase chain reaction (Heminested-PCR) was designed to target the
      16S rRNA fragment simultaneously using a set of primers for the universal
      bacterial group and a Neisseria meningitidis species-specific sequence for
      diagnostic purposes. The diagnostic features of the Heminested-PCR were evaluated
      in the study of 168 cerebrospinal fluid (CSF) specimens from 84 patients with a
      N. meningitidis infection, meningitis caused by unrelated bacteria and other
      etiologies (57 patients), or suspicious cases (27 patients) with clinical
      symptoms of bacterial meningitis but with negative results from bacteriological
      procedures. About 90% of patients with bacterial meningitis, including those
      suspicious cases, had prior antibiotic therapy. The sensitivity, specificity,
      positive, and negative predictive values found in relation to culture and/or
      microscopy were 91.7, 100, 100, 100, and 90.5%, respectively. In patients
      suspected of having bacterial meningitis, the Heminested-PCR revealed 51.9% (14
      patients) positive for N. meningitidis infection and 40.7% (11 patients) positive
      for unrelated bacterial infections. The agreement of the Heminested-PCR with
      culture and/or microscopy was high and ranked as almost perfect (kappa indices >
      0.856), in contrast to its agreement with other techniques. These findings speak
      in favor of the molecular diagnosis of meningococcal meningitis in patients who
      are culture- and/or microscopy-negative, due to their prior antibiotic treatment.

PMID- 10906774
TI  - Regulation and function of Dlx3 in vertebrate development.
AB  - Dlx3 is a homeodomain transcription factor in vertebrates, related to Distal-less
      in Drosophila, that is expressed in differentiating epidermal cells, in neural
      crest, hair follicles, dental epithelium and mesenchyme, the otic and olfactory
      placodes, limb bud, placenta, and in the cement gland, which is located in the
      extreme anterior neural plate in Xenopus embryos. This factor behaves as a
      transcriptional activator, and positively regulates gene expression in the skin,
      and negatively regulates central nervous system markers in Xenopus epidermis and
      anterior neural plate. A mutation in the DLX3 gene is associated with a
      hereditary syndrome in humans, and loss of Dlx3 function is a developmental
      lethal in gene-targeted mice, where it is essential for proper modeling of the
      labyrinthine layer of the placenta. In this review, we discuss the evolution,
      expression, regulation, and function of Dlx3 in mouse, amphibians, and zebrafish.
      Published 2000 Wiley-Liss, Inc.

PMID- 10906776
TI  - Expression of TGF-beta stimulated clone-22 (TSC-22) in mouse development and TGF
      beta signalling.
AB  - TSC-22 is a highly conserved member of a novel family of transcription factors,
      that is a direct target of transforming growth factor-beta (TGF-beta) in
      osteoblastic cells. We have investigated the expression of TSC-22 in detail
      during mouse development using in situ hybridization. We detected strong
      expression of TSC-22 in the embryo proper first at embryonic day 8.5 (E8.5), in
      the primitive heart, intermediate mesoderm and the neural tube. The dynamics of
      the TSC-22 distribution in the neural tube was particularly striking, with
      ubiquitous expression rostrally and restriction to neural tissue nearer the floor
      plate more caudally; between E8.5 and E9.5 the zone of restricted expression
      extended rostrally. At later stages of development, TSC-22 was detected in the
      mesenchymal compartment of many tissues and organs, including the lung, trachea,
      kidney, stomach, intestine, tooth buds, and in precartilage condensations.
      Furthermore, TSC-22 was highly expressed in the floor plate itself and notochord,
      and the endothelium lining the blood vessels, in particular the major arteries.
      Many of these sites have been proposed previously as possible TGF-beta target
      tissues; the results imply that TSC-22 may also be a direct TGF-beta target gene
      during mouse embryogenesis. Experiments on TSC-22 expression in embryoid bodies
      of embryonic stem (ES) cells expressing dominant negative TGF-beta binding
      receptors initially supported this hypothesis. However, examination of somatic
      chimeras derived from these same mutant ES cells at nominal E9.5 showed that TSC
      22 expression in the heart and neural tube was still detectable despite obvious
      phenotypic abnormalities. We therefore propose that although TSC-22 may be a
      direct target of TGF-beta in late development, other factors are likely to be
      major regulators of expression at earlier stages.

PMID- 10906775
TI  - Distal-less function during Drosophila appendage and sense organ development.
AB  - The Drosophila Distal-less (Dll) gene was identified in the early 1980s by means
      of dominant and recessive mutations that caused both striking antenna-to-leg
      transformations and leg truncations. The gene initially was named "Bristle on
      arista" or "Brista" because one aspect of the phenotype is the formation of leg
      bristles on the antenna (Sato [1984] Drosophila Information Service 60:180-182;
      Sunkel and Whittle [1987] Wilhelm Roux's. Arch. Dev. Biol. 196:124-132).
      Subsequent studies have revealed that Dll encodes a homeodomain transcription
      factor (Cohen et al. [1989] Nature 338:432-434) that is expressed throughout limb
      development from embryogenesis on (Cohen [1990] Nature 343:173-177; Weigmann and
      Cohen [1999] Development 126:3823-3830). Dll is required for the elaboration of
      distal pattern elements in the antenna, the legs, the limb-derived gnathal
      structures (Cohen and Jurgens [1989] Nature 482-485), and the anal plate
      (Gorfinkiel et al. [1999] Mech. Dev. 868:113-123) and can initiate proximodistal
      axis formation when expressed ectopically (Gorfinkiel et al. [1997] Genes Dev.
      11:2259-2271). Dll homologs are expressed in developing appendages in at least
      six coelomate phyla, including chordates (Akimenko et al. [1994] J. Neurosci.
      14:3475-3486; Beauchemin and Savard [1992] Dev. Biol. 154:55-65; Bulfone et al.
      [1993] Mech. Dev. 40:129-140; Dolle et al. [1992] Differentiation 49:93-99;
      Ferrari et al. [1995] Mech. Dev. 52:257-264; Panganiban et al. [1997] Proc. Natl.
      Acad. Sci. USA 94:5162-5166; Simeone et al. [1994] Proc. Natl. Acad. Sci. USA
      91:2250-2254), consistent with requirements for Dlx function in normal limb
      development across the animal kingdom. Distal-less also has been implicated in
      various aspects of vertebrate neurogenesis (see reviews by Kraus and Lufkin
      [1999] J. Cell. Biochem. 32-33:133-140 and the accompanying review by Beanan and
      Sargent [2000] Dev. Dyn. 218:000-000). Here, I outline what is known about Dll
      function and regulation in Drosophila.

PMID- 10906777
TI  - Skeletal-specific expression of Fgd1 during bone formation and skeletal defects
      in faciogenital dysplasia (FGDY; Aarskog syndrome).
AB  - FGD1 encodes a guanine nucleotide exchange factor (GEF) that specifically
      activates the Rho GTPase Cdc42; FGD1 mutations result in Faciogenital Dysplasia
      (FGDY, Aarskog syndrome), an X-linked developmental disorder that adversely
      affects the formation of multiple skeletal structures. To further define the role
      of FGD1 in skeletal development, we examined its expression in developing mouse
      embryos and correlated this pattern with FGDY skeletal defects. In this study, we
      show that Fgd1, the mouse FGD1 ortholog, is initially expressed during the onset
      of ossification during embryogenesis. Fgd1 is expressed in regions of active bone
      formation in the trabeculae and diaphyseal cortices of developing long bones. The
      onset of Fgd1 expression correlates with the expression of bone sialo-protein, a
      protein specifically expressed in osteoblasts at the onset of matrix
      mineralization; an analysis of serial sections shows that Fgd1 is expressed in
      tissues containing calcified and mineralized extracellular matrix. Fgd1 protein
      is specifically expressed in cultured osteoblast and osteoblast-like cells
      including MC3T3-E1 cells and human osteosarcoma cells but not in other mesodermal
      cells; immunohistochemical studies confirm the presence of Fgd1 protein in mouse
      calvarial cells. Postnatally, Fgd1 is expressed more broadly in skeletal tissue
      with expression in the perichondrium, resting chondrocytes, and joint capsule
      fibroblasts. The data indicate that Fgd1 is expressed in a variety of regions of
      incipient and active endochondral and intramembranous ossification including the
      craniofacial bones, vertebrae, ribs, long bones and phalanges. The observed
      pattern of Fgd1 expression correlates with FGDY skeletal manifestations and
      provides an embryologic basis for the prevalence of observed skeletal defects.
      The observation that the induction of Fgd1 expression coincides with the
      initiation of ossification strongly suggests that FGD1 signaling plays a role in
      ossification and bone formation; it also suggests that FGD1 signaling does not
      play a role in the earlier phases of skeletogenesis. With the observation that
      FGD1 mutations result in the skeletal dysplasia FGDY, accumulated data indicate
      that FGD1 signaling plays a critical role in ossification and skeletal
      development.

PMID- 10906778
TI  - Both smooth and skeletal muscle precursors are present in foetal mouse oesophagus
      and they follow different differentiation pathways.
AB  - Muscularis externa of mouse oesophagus is composed of two skeletal muscle layers
      in the adult. Unlike rest of skeletal muscle in the body, the oesophageal
      skeletal muscle in the mouse has been proposed to be derived from fully
      differentiated smooth muscle cells by transdifferentiation during later foetal
      and early postnatal development (Patapoutian et al. [1995] Science 270:1818
      1821). Here we characterised the nature of cells in muscularis externa of the
      mouse oesophagus by ultrastructural and immunoctyochemical analyses. The presence
      of differentiated skeletal muscle cells identified by positive staining for
      skeletal muscle specific myosin heavy chain became first apparent in the outer
      layer of cranial oesophagus at 14 days gestation. The transient expression of
      smooth muscle type alpha-actin in mouse oesophageal muscle was also apparent
      during foetal development. This isoform, however, was not smooth muscle specific
      during early development as it was also detected in foetal skeletal muscles.
      Compared with oesophagus, the suppression of this smooth muscle type alpha-actin
      during foetal development was faster in non-oesophageal skeletal muscle cells.
      The development of skeletal muscle in oesophagus showed a cranial to caudal and
      an outer layer to inner layer progression. During early foetal development, mouse
      oesophagus is composed of undifferentiated mesenchymal cells that formed cell
      clusters. Two types of cells with different staining densities could be
      distinguished within these cell clusters by electron microscopy. The centrally
      located pale staining cells gave rise to skeletal muscle cells while the
      peripherally positioned dense staining cells gave rise to smooth muscle cells,
      indicating the existence of both skeletal and smooth muscle cell precursors in
      mouse oesophagus during early foetal development. Further development showed an
      increase in the proportion of skeletal muscle cells and a decrease in size and
      number of the smooth muscle type cells. Apart from decrease in cell size, some
      other morphological features of smooth muscle cell degeneration were also
      observed during later foetal and early neonatal development. No smooth muscle
      cells undergoing transdifferentiation were observed. Both immunochemical and
      ultrastructural observations, thus, demonstrated the presence of skeletal muscle
      cells in early foetal oesophagus. It is concluded that the transient appearance
      of smooth muscle cells may provide a scaffold for the laying down of skeletal
      muscle layers in mouse oesophagus, the final disappearance of which may be
      triggered by lack of smooth muscle innervation.

PMID- 10906779
TI  - An MCM2-related gene is expressed in proliferating cells of intact and
      regenerating planarians.
AB  - The minichromosome maintenance (MCM2-7) gene family encodes conserved proteins,
      which are essential for DNA replication licensing in eukaryotes. They are
      abundant in proliferating cells, and specific MCM transcripts undergo cell cycle
      dependent oscillations. Here we report the characterization of a planarian MCM2
      homologue, DjMCM2, which represents the first molecular marker for detecting
      proliferating cells in planarians. DjMCM2-expressing cells are broadly
      distributed in the mesenchymal space of the body, with the exception of the
      cephalic region, and are preferentially accumulated in the peripheral area of the
      dorso-lateral mesenchyme, along the anteroposterior axis. During regeneration, no
      DjMCM2 transcripts are observed within the blastema, according to the current
      view that this structure is not a proliferation site in planarians. Spatio
      temporal changes in DjMCM2 RNA expression pattern in the stump parallel blastema
      growth, coordinately with the orientation of the cut. X-ray irradiation results
      in the disappearance of DjMCM2 expression, thus confirming that these transcripts
      are detected specifically in proliferating cells, visualized as neoblasts by in
      situ hybridization in dissociated cells. In addition to neoblasts, rare large
      DjMCM2-expressing cells are observed in macerates of tissues excised just below
      the wound, suggesting that cell types other than neoblasts may be sporadically
      recruited for proliferation in planarians.

PMID- 10906780
TI  - Development of the pancreas in Xenopus laevis.
AB  - Xenopus embryos have several experimental advantages for studying development.
      Although these advantages have traditionally been used to elucidate mechanisms of
      early development, they can also be exploited to investigate issues later in
      development such as organogenesis. We have begun to study pancreatic
      organogenesis in Xenopus. Using histological and molecular marker analysis, we
      characterized the anatomy of the developing pancreas in Xenopus embryos from the
      time of initial pancreatic rudiment formation to the time when the tadpole starts
      to feed. We examined the expression of various endocrine hormones, exocrine gene
      products, and pancreatic transcription factors. Interestingly, the endocrine
      hormone insulin has restricted expression in the dorsal pancreas. Investigation
      of pancreatic specification during gastrulation demonstrates that insulin
      expression is regionalized along the dorsoventral axis early in development.

PMID- 10906781
TI  - Histone acetylation is a checkpoint in FGF-stimulated mesoderm induction.
AB  - We have previously demonstrated that the transcription factor, AP-1 (c-jun/c-fos
      heterodimer), mediates fibroblast growth factor (FGF) signaling during mesoderm
      induction in Xenopus embryo. In the present studies, we show that histone
      acetylation is involved in FGF-mediated signaling leading to mesoderm induction.
      Histone acetylation is a dynamic process regulated by the activities of two
      histone-modifying enzymes, the histone acetyltransferase(s) and histone
      deacetylase(s) (HDACs). We found that basal and FGF-regulated activator protein 1
      (AP-1) activity in Xenopus embryo is markedly reduced by treatment of
      trichostatin A (TSA), a specific inhibitor of HDAC. However, activity of another
      transcription factor, NFkappaB, is enhanced by TSA treatment. AP-1-mediated
      mesoderm induction in the animal caps is dramatically suppressed by TSA at a dose
      dependent manner. This suppression can be rescued by ectopic expression of HDAC3
      at early stage. Finally, we found that histone acetylation in animal caps is
      inhibited by FGF whereas enhanced by TSA (as a control). Therefore, we propose
      that histone acetylation is a checkpoint for transduction of the FGF/AP-1 signals
      to induce mesoderm. Published 2000 Wiley-Liss, Inc.

PMID- 10906783
TI  - Selective assembly and remodelling of collagens II and IX associated with
      expression of the chondrocyte hypertrophic phenotype.
AB  - The assembly and resorption of the extracellular matrix in the physis of the
      growth plate are poorly understood. By examining isolated fetal growth plate
      chondrocytes in culture and using immunochemical methods we show that type II
      collagen, proteoglycan aggrecan, and type IX collagen are assembled into a matrix
      that is initially enriched in type II collagen over proteoglycan and type IX
      collagen. When compared to the content of the COL2 domain in the alpha(1)(IX)
      chain it is evident that the majority ( 90%) of type IX molecules lack the NC4
      domain unlike in articular cartilage. During matrix assembly the molar ratio of
      type II/COL2 of alpha(1)(IX) varied from 25:1 to 2.5:1. Following expression of
      the hypertrophic phenotype (initiation of type X collagen synthesis) there are
      parallel changes in both collagen and proteoglycan contents (inversely related to
      collagenase cleavage of type II collagen). The NC4 domain is then selectively,
      rapidly and irreversibly removed as mineralization is initiated, leaving the
      alpha(1)(IX) chain COL2 domain. Subsequently as mineralization progresses type II
      and type IX collagen (COL2 domain), but not the proteoglycan aggrecan, are
      resorbed coincident with a markedly increased cleavage of type II collagen by
      collagenase as mineral is deposited in the matrix. This study, therefore reveals
      a carefully orchestrated series of events in matrix assembly and resorption that
      prepares the extracellular matrix for mineralization.

PMID- 10906782
TI  - Changes in HOXB6 homeodomain protein structure and localization during human
      epidermal development and differentiation.
AB  - HOX homeodomain proteins are master developmental regulators, which are now
      thought to function as transcription factors by forming cooperative DNA binding
      complexes with PBX or other protein partners. Although PBX proteins exhibit
      regulated subcellular localization and function in the nucleus in other tissues,
      little data exists on HOX and PBX protein localization during skin development.
      We now show that the HOXB6 protein is expressed in the suprabasal layer of the
      early developing epidermis and throughout the upper layers of late fetal and
      adult human skin. HOXB6 signal is cytoplasmic throughout fetal epidermal
      development, but substantially nuclear in normal adult skin. HOXB6 protein is
      also partially nuclear in hyperproliferative skin conditions, but appears to be
      cytoplasmic in basal and squamous cell carcinomas. Although all three PBX genes
      are expressed in fetal epidermis, none of the three PBX proteins exhibit nuclear
      co-localization with HOXB6 in either fetal or adult epidermis. RNA and protein
      data suggest that a truncated HOXB6 protein, lacking the homeodomain, is
      expressed in undifferentiated keratinocytes and that the full-length protein is
      induced by differentiation. GFP-fusion proteins were used to demonstrate that the
      full-length HOXB6 protein is localized to the nucleus while the truncated protein
      is largely cytoplasmic. Taken together, these data suggest that during epidermal
      development the truncated HOXB6 isoform may function by a mechanism other than as
      DNA binding protein, and that most of the nuclear, homeodomain-containing HOXB6
      protein does not utilize PBX proteins as DNA binding partners in the skin.
      Published 2000 Wiley-Liss, Inc.

PMID- 10906784
TI  - Expression of the inhibitory Smad7 in early mouse development and upregulation
      during embryonic vasculogenesis.
AB  - SMAD proteins are downstream targets of serine/threonine kinase receptors of the
      transforming growth factor beta (TGF beta) superfamily. Ligands activating these
      receptors regulate cell growth, differentiation and development in many tissues
      of various organisms. In mammals eight different Smad genes are known, each with
      different roles in mediating signalling between plasma membrane and nucleus.
      Smad6 and Smad7 are inhibitors of TGF beta family signalling. They are both
      expressed in human adult vascular endothelial cells, particularly after these
      cells have been subjected to shear stress (Topper et al. [1997] Proc Natl Acad
      Sci USA 94:9314-9319). Here we show by reverse transcriptase polymerase chain
      reaction and in situ hybridization that Smad7 mRNA is highly expressed in the
      developing vascular system of the mouse embryo but is also detectable much
      earlier in preimplantation embryos and during gastrulation. We also demonstrate
      by transient transgenesis that overexpression of Smad7 in mouse zygotes inhibits
      development beyond the 2-cell stage. This confirms earlier conclusions of
      similar, but complementary, experiments using a dominant negative type II TGF
      beta receptor demonstrating that TGF beta signalling is required for normal
      preimplantation development.

PMID- 10906787
TI  - Developing trends

PMID- 10906786
TI  - Extent of ossification at the amputation plane is correlated with the decline of
      blastema formation and regeneration in Xenopus laevis hindlimbs.
AB  - Xenopus laevis larvae gradually lose the ability to regenerate lost hindlimb
      structures as they progress through metamorphosis. Previous studies have
      suggested that this loss of regenerative capacity occurs in a proximal-to-distal
      fashion. We assessed the quality of overall regeneration and early bud blastema
      formation in order to evaluate previous explanations for this loss of
      regenerative ability in Xenopus. We further examined the extent to which
      epidermis, basement membrane, dermis, cartilage, bone, periosteum, and
      accumulated mesenchyme within the blastema are involved in the decline of
      regenerative abilities during mid-metamorphic stages of development. Each tissue
      was scored based on its contributions to the regeneration blastema, in accordance
      with previously reported blastemal descriptions. Tadpoles amputated at the ankle
      and tarsal-metatarsal joints scored objectively higher within the overall
      regeneration and blastema quality rating systems. Both joint sites met more
      criteria associated with regeneration-capable blastemas than tadpoles amputated
      through the middle of the tarsus, especially at later stages of metamorphosis.
      The three amputation sites studied began to vary in their ability to regenerate
      skeletal elements and to generate productive blastemas during the same stages at
      which we initially observed ossification of the tarsus. These results suggest
      that the decline of Xenopus hindlimb regeneration does not occur in a strictly
      proximal-to-distal fashion but rather is dependent at later stages on the state
      of ossification of the structure through which amputation occurs. Our
      morphological and cellular observations reveal specific times and places during
      Xenopus hindlimb development at which further investigations into tissue-specific
      molecular events during early regeneration should be focused.

PMID- 10906785
TI  - Interaction of Frizzled 7 and Dishevelled in Xenopus.
AB  - Frizzled proteins act as putative Wnt receptors and depending on Wnt/Frizzled
      interactions distinct intracellular pathways can be activated. The canonical Wnt
      pathway, triggered by Wnt-1-type ligands, is the best characterized and involves
      the activation of the cytoplasmic protein Dishevelled (Dsh). The Xenopus frizzled
      7 receptor (Xfz7) can act in the canonical (Wnt-1-type) as well as in a non
      canonical Wnt pathway which involves the activation of protein kinase C (PKC). In
      order to analyze the interaction between Xfz7 and Xdsh protein, we tested the
      effect of overexpression of Xfz7 on the subcellular distribution of Xdsh-myc
      protein. We demonstrate that Xfz7 can recruit Xdsh-myc to the plasma membrane and
      target genes of the Wnt-1-type pathway such as siamois and nodal related 3 (Xnr
      3) are only activated in the presence of exogenous Xdsh-myc. Xfz7 in combination
      with Xwnt-8b, however, is able to induce siamois even in the absence of Xdsh-myc.
      Similar results were obtained after expression of Human frizzled 5 (Hfz5)
      together with Xwnt-5a but this receptor-ligand combination recruits Xdsh-myc only
      very poorly to the membrane. These results suggests that the endogenous Xdsh pool
      and exogenous Xdsh-myc differ in their ability to be recruited by Frizzled
      receptors.

PMID- 10906788
TI  - Ear rings: FGF3 involvement comes full circle.

PMID- 10906789
TI  - Down to less than 300 genes: the DNA sequence of human chromosome 21 and Down's
      syndrome.

PMID- 10906790
TI  - Turning off the anxiety master switch.

PMID- 10906791
TI  - Nerves - the silent but strong type.

PMID- 10906792
TI  - Social barriers to a theoretical neuroscience.
AB  - Social rather than scientific barriers are impeding neuroscience theory. There
      are plenty of experimental data and mathematical methods to develop a rigorous,
      mathematical theory in neuroscience. However, structural mathematical efforts are
      being suffocated by the requirement to produce numbers immediately. Also
      theoretical development is tied too closely to one experimental group. The social
      barriers can be addressed by: (1) judging theory by structural accuracy rather
      than numerical output; (2) recognizing mathematical theory (not just
      computational modeling) as a method for producing insight into neurobiological
      phenomena; (3) funding fundamental theoretical neuroscience and (4) recognizing
      theoretical neuroscientists as neuroscientists.

PMID- 10906793
TI  - Xenotransplantation for CNS repair: immunological barriers and strategies to
      overcome them.
AB  - Neural transplantation holds promise for focal CNS repair. Owing to the shortage
      of human donor material, which is derived from aborted embryos, and ethical
      concerns over its use, animal donor tissue is now considered an appropriate
      alternative. In the USA, individuals suffering from Parkinson's disease,
      Huntington's disease, focal epilepsy or stroke have already received neural
      grafts from pig embryos. However, in animal models, neural tissue transplanted
      between species is usually promptly rejected, even when implanted in the brain.
      Some of the immunological mechanisms that underlie neural xenograft rejection
      have recently been elucidated, but others remain to be determined and controlled
      before individuals with neurological disorders can benefit from
      xenotransplantation.

PMID- 10906796
TI  - Reply to vazdarjanova

PMID- 10906795
TI  - Does the basolateral amygdala store memories for emotional events?

PMID- 10906797
TI  - Emx homeogenes and mouse brain development.
AB  - Mammalian homeogenes of the Emx family, Emx1 and Emx2, are expressed in the
      developing cerebral cortex and are involved in the patterning of the rostral
      brain. Although very little is known about the role of Emx1, details of the
      function of EMX2 are emerging from the observation of cortical phenotypes in
      normal and mutant mice. Emx2 is expressed in proliferating neuroblasts and in the
      so-called postmitotic Cajal-Retzius cells, known to control migration of cortical
      neurons. The graded distribution of EMX2 homeoprotein suggests a potential role
      for Emx2 in the subdivision of the cortex into territories and possibly areas.

PMID- 10906798
TI  - Neuronal migration disorders: from genetic diseases to developmental mechanisms.
AB  - Neurons that constitute the cerebral cortex must migrate hundreds of cell-body
      distances from their place of birth, and through several anatomical boundaries,
      to reach their final position within the correct cortical layer. Human
      neurological conditions associated with abnormal neuronal migration, together
      with spontaneous and engineered mouse mutants, define at least four distinct
      steps in cortical neuronal migration. Many of the genes that control neuronal
      migration have strong genetic or biochemical links to the cytoskeleton,
      suggesting that the field of neuronal migration might be closing in on the
      underlying cytoskeletal events.

PMID- 10906799
TI  - The hypocretin/orexin ligand-receptor system: implications for sleep and sleep
      disorders.
AB  - The molecules originally described as the hypocretins and subsequently as the
      orexins were initially implicated in the control of food intake. Recent
      observations implicate this newly-described neurotransmitter system in the sleep
      disorder narcolepsy and, potentially, in the regulation of normal sleep
      processes. This article reviews the research that led to the isolation of the
      hypocretin/orexin peptides, their receptors and the activity of these molecules
      as we currently understand them. A model is proposed in which the cells that make
      these peptides might be involved in arousal state control.

PMID- 10906800
TI  - Ca2+-Zn2+ permeable AMPA or kainate receptors: possible key factors in selective
      neurodegeneration.
AB  - Neurological diseases, including global ischemia, Alzheimer's disease and
      amyotrophic lateral sclerosis, are characterized by selective patterns of
      neurodegeneration. Most studies of potential glutamate-receptor-mediated
      contributions to disease have focused on the highly Ca2+-permeable and widely
      distributed NMDA-receptor channel. However, an alternative hypothesis is that the
      presence of AMPA- or kainate-receptor channels that are directly permeable to
      Ca2+ ions (Ca-A/K-receptor channels) is of greater significance to the neuronal
      loss seen in these conditions. Besides a restricted distribution and high Ca2+
      permeability, two other factors make Ca-A/K receptors appealing candidate
      contributors to selective injury: their high permeability to Zn2+ ions and the
      possibility that their numbers increase in disease-associated conditions. Further
      characterization of the functions of these channels should result in new
      approaches to treatment of these conditions.

PMID- 10906801
TI  - On the origin of skilled forelimb movements.
AB  - Homologizing behaviour was once considered unreliable, but the application of
      modern comparative methods has been shown to provide strong evidence of
      behavioural homologies. Skilled forelimb movements were thought to originate in
      the primate lineage but in fact are common among tetrapod taxa and probably share
      a common origin in early tetrapods. Furthermore, skilled movements are likely to
      have been derived from, and elaborated through, food-handling behaviour. In
      addition, it is now thought that the role played by the lateral and medial
      descending pathways of the spinal cord in the execution of skilled forelimb
      movements could be synergistic, rather than the exclusive responsibility of an
      individual pathway.

PMID- 10906802
TI  - HIV and infant feeding: is breast the best?

PMID- 10906803
TI  - Age related seroprevalence of antibodies to varicella in India.
AB  - OBJECTIVE: To determine the age related prevalence of Varicella Zoster Virus
      (VZV) antibodies in India. SETTING: This was a cross sectional multicentric study
      performed in 4 major cities of India: Calcutta (outpatients), Mumbai
      (outpatients), Lucknow (walk-in patients to a diagnostic laboratory, orphanage
      and factory workers) and Bangalore (outpatients and walk-in patients to a
      diagnostic laboratory). METHODS: A total of 1609 volunteers from birth to 40
      years of age were included into the study. IgG antibodies against VZV were
      determined using commercial kits (ELISA-Enzygnost). RESULTS: Overall
      seroprevalence of anti VZV antibodies was 68. 22percnt. The age related
      seroprevalence rate of anti VZV antibodies was 29percnt in the age group of 1-5
      years, 51.1percnt in 5-10 years, 71.7percnt in 11-15 years, 79.8percnt in 16-20
      years, 88.1percnt in 21-30 years and 91.1percnt in 31-40 years. CONCLUSION: A
      significant proportion of adolescents and adults are susceptible to varicella in
      India, as in other tropical countries

PMID- 10906804
TI  - Protein energey malnutrition and skeletal muscle wasting in childhood acute
      lymphoblastic lukemia.
AB  - OBJECTIVE: To determine the nutritional status and the extent of skeletal muscle
      wasting in children with acute lymphoblastic leukemia (ALL) at the time of
      diagnosis and after induction chemotherapy. DESIGN: Prospective observational
      study. SETTING: Tertiary care teaching hospital. METHODS: 25 new cases of ALL
      underwent somatometric measurements and ultrasonographic evaluation of skeletal
      muscle and subcutaneous fat at initial presentation and after completion of
      induction therapy. RESULTS: Malnutrition (weight for age < 80percnt) was evident
      in 13 cases (52percnt), but cumulative incidence of malnutrition (weight for age
      < 80percnt, weight for height < 90percnt, height for age < 95percnt, skin fold
      thickness < 5th centile, midarm muscle circumference < 5th centile) was 88percnt.
      Nine children lost weight during induction (range: 0.2 to 5.8 kg; means +/- SD:
      1.9 plusmn 1.8 kg). All these cases had a complicated course during induction
      chemotherapy. Fourteen children (56percnt) had skeletal muscle wasting during
      induction chemotherapy. All those children who had lost weight also had skeletal
      muscle wasting. Subcutaneous fat, in contrast increased in 24 cases (96percnt).
      CONCLUSION: Malnutrition exists in a significant proportion of children with ALL.
      If induction chemotherapy is complicated, children lose significant weight and
      have significant muscle wasting. Increase in subcutaneous fat occurs in almost
      all children, which is probably a consequence of therapy with oral steroids

PMID- 10906805
TI  - Diphtheria-down but not out.

PMID- 10906806
TI  - Basic philosophy of statistical tests, confidence intervals and sample size
      determination.

PMID- 10906807
TI  - Use of 'Fixed' combination preparations of inhaled short acting b-2 agonists and
      inhaled corticosteroids.

PMID- 10906808
TI  - Prevalence of minor injuries among underfives in a Chandigarh slum.

PMID- 10906809
TI  - Langerhans cell histiocytosis with organ dysfunction.

PMID- 10906810
TI  - Experience of pediatric tetanus cases from Mumbai.

PMID- 10906811
TI  - Non-invasive estimation of total serum bilirubin by multi-wavelength spectral
      reflectance in neonates.

PMID- 10906812
TI  - Risk of early onset neonatal septicemia in babies born to mothers with pre
      eclampsia.

PMID- 10906813
TI  - Infantile hepatic hemangio-endothelioma: treatment by coil embolization of the
      hepatic artery.

PMID- 10906814
TI  - Fetal and neonatal extrasystoles.

PMID- 10906815
TI  - A child with prolonged pyrexia and peripheral desquamation: is it Kawasaki
      disease?

PMID- 10906817
TI  - Transmission of live vaccine viruses from vaccinated persons to others.

PMID- 10906816
TI  - Cranio-spinal granulocytic sarcomas in childhood acute myeloid leukemia.

PMID- 10906818
TI  - Transmission of live vaccine viruses from vaccinated persons to others - reply

PMID- 10906820
TI  - Should tetanus toxoid be administered every 5 years - reply

PMID- 10906819
TI  - Should tetanus toxoid be administered every 5 years.

PMID- 10906821
TI  - Urogenital myiasis.

PMID- 10906822
TI  - Omphalopagus.

PMID- 10906823
TI  - Adrenaline for septic shock in newborn.

PMID- 10906824
TI  - Pitfalls in the diagnosis of esophageal atresia.

PMID- 10906825
TI  - An unusual case of lightning injury.

PMID- 10906826
TI  - Albendazole-the magic bullet for prevention of stunting in Indian children.

PMID- 10906827
TI  - Albendazole-The magic bullet for prevention of stunting in indian children -
      reply

PMID- 10906828
TI  - Health and nutrition problems and health care seeking practices of rural women
      and children-lessons for health and nutrition entrepreneur's training.

PMID- 10906829
TI  - Down's syndrome with transient abnormal myelofibrosis.

PMID- 10906830
TI  - Association between medications that relax the lower esophageal sphincter and
      risk for esophageal adenocarcinoma.
AB  - BACKGROUND: The incidence of esophageal adenocarcinoma is increasing rapidly.
      Gastroesophageal reflux is a strong risk factor for this disease. The increase in
      incidence of esophageal adenocarcinoma coincided with the introduction of
      medications that promote reflux by relaxing the lower esophageal sphincter (LES),
      such as nitroglycerin, anticholinergics, beta-adrenergic agonists,
      aminophyllines, and benzodiazepines. OBJECTIVE: To test the possible association
      between use of LES-relaxing medications and risk for adenocarcinoma of the
      esophagus and gastric cardia. DESIGN: A nationwide population-based case-control
      study with in-person interviews. SETTING: Sweden, 1995 through 1997. PATIENTS:
      189 patients with newly diagnosed esophageal adenocarcinoma, 262 with
      adenocarcinoma of the gastric cardia, and 167 with esophageal squamous-cell
      carcinoma were compared with 820 population-based controls. MEASUREMENTS:
      Estimated incidence rate ratios, calculated by using multivariate logistic
      regression from case-control data with adjustment for potential confounding.
      RESULTS: Past use of LES-relaxing drugs was positively associated with risk for
      esophageal adenocarcinoma. Among daily, long-term users (>5 years) of LES
      relaxing drugs, the estimated incidence rate ratio was 3.8 (95% CI, 2.2 to 6.4)
      compared with persons who had never used these drugs. Drugs of all classes
      contributed to the increased risk, but the association was particularly strong
      for anticholinergics. Short-term use of other types of LES-relaxing drugs did not
      seem to be strongly associated with risk. The association almost disappeared
      after adjustment for reflux symptoms, indicating that promotion of reflux is the
      link between use of LES-relaxing drugs and esophageal adenocarcinoma. If 15,490
      men in any age group take LES-relaxing drugs daily for 5 years, 1 additional case
      of adenocarcinoma would be expected (number needed to treat for harm); in men
      older than 60 years of age, the number needed to treat for harm is 5,570.
      Assuming a causal relation, about 10% of the esophageal adenocarcinomas occurring
      in the population may be attributable to intake of LES-relaxing drugs. Cardia
      adenocarcinoma and esophageal squamous-cell carcinoma were not associated with
      use of LES-relaxing drugs. CONCLUSIONS: The widespread use of LES-relaxing drugs
      may have contributed to the increasing incidence of esophageal adenocarcinoma.

PMID- 10906831
TI  - The fetal and childhood growth of persons who develop type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes is associated with low birthweight followed by
      obesity in adulthood. Persons who develop the disease may therefore have a
      particular pattern of growth from birth through childhood. OBJECTIVE: To examine
      the relation of type 2 diabetes to size at birth and childhood growth. DESIGN:
      Cohort study. SETTING: Helsinki, Finland. PARTICIPANTS: Men (n = 3,639) and women
      (n = 3,447) who were bom at the Helsinki University Central Hospital between 1924
      and 1933, who went to school in Helsinki, and who still lived in Finland in 1971.
      Detailed birth and school health records were available for all 7,086
      participants. We identified 471 men and women who developed type 2 diabetes by
      using the national Social Insurance Institution's register of all persons in
      Finland who are receiving long-term therapy with medication. MEASUREMENTS:
      Incidence of diabetes ascertained from a national register. The main explanatory
      measurements were size at birth and childhood growth in terms of height, weight,
      and body mass index. RESULTS: The cumulative incidence of type 2 diabetes was
      7.9% (n = 286) in men and 5.4% (n = 185) in women. The incidence increased with
      decreasing birthweight, birth length, ponderal index (birthweight/length(3)), and
      placental weight The odds ratio for type 2 diabetes was 1.38 (95% CI, 1.15 to
      1.66; P < 0.001) for each 1-kg decrease in birthweight. The mean weights and
      heights of the children at 7 years of age who later developed type 2 diabetes
      were about average. Thereafter, their growth in weight and height was accelerated
      until 15 years of age. The odds ratio for development of type 2 diabetes was 1.39
      (CI, 1.21 to 1.61; P < 0.001) for each standard deviation increase in weight
      between 7 and 15 years of age. The odds ratio became 1.83 (CI, 1.37 to 2.45; P<
      0.001) in an analysis restricted to persons whose birthweights were below 3,000
      g. Children of both sexes whose mothers had a high body mass index in pregnancy
      had more rapid growth during childhood and an increased incidence of type 2
      diabetes. CONCLUSIONS: These findings are consistent with the hypothesis that
      type 2 diabetes is programmed in utero in association with low rates of fetal
      growth. The increased risk for type 2 diabetes associated with small size at
      birth is further increased by high growth rates after 7 years of age.

PMID- 10906832
TI  - Cigarette smoking and risk for impaired fasting glucose and type 2 diabetes in
      middle-aged Japanese men.
AB  - BACKGROUND: The contribution of cigarette smoking to development of impaired
      fasting glucose and type 2 diabetes remains unclear. OBJECTIVE: To investigate
      the association of cigarette smoking with development of impaired fasting glucose
      and type 2 diabetes. DESIGN: Prospective cohort study. SETTING: Work site in
      Osaka, Japan. PARTICIPANTS: 1,266 Japanese male office workers 35 to 59 years of
      age who did not have impaired fasting glucose or type 2 diabetes and were not
      taking medication for hypertension at study entry. MEASUREMENTS: Fasting plasma
      glucose levels were measured at annual health examinations from May 1994 through
      May 1999. Impaired fasting glucose was defined as a fasting glucose level of at
      least 6.1 mmol/L (110 mg/dL) but less than 7.0 mmol/L (126 mg/dL). Type 2
      diabetes was defined as a fasting glucose level of 7.0 mmol/L or more or current
      receipt of hypoglycemic medication. RESULTS: 87 and 54 men developed impaired
      fasting glucose and type 2 diabetes during 5,817 and 5,937 person-years follow
      up, respectively. After controlling for potential predictors of diabetes, the
      relative risk for impaired fasting glucose compared with never-smokers was 1.62
      (95% CI, 0.85 to 3.10) for ever-smokers, 1.14 (CI, 0.58 to 2.25) for persons who
      smoked 1 to 20 cigarettes/d, 1.33 (CI, 0.63 to 2.80) for those who smoked 21 to
      30 cigarettes/d, and 2.56 (CI, 1.32 to 4.95) for those who smoked 31 or more
      cigarettes/d (P for trend for current smokers only = 0.013). The respective
      multivariate-adjusted relative risks for type 2 diabetes compared with never
      smokers were 1.08 (CI, 0.34 to 3.42), 1.88 (CI, 0.71 to 5.00), 3.02 (CI, 1.15 to
      7.94), and 4.09 (CI, 1.62 to 1,029) (P for trend for current smokers only <
      0.001). The number of pack-years of exposure was also positively related to
      development of impaired fasting glucose and type 2 diabetes (P for trend = 0.039
      and 0.002, respectively). The relative risk for impaired fasting glucose and type
      2 diabetes in current smokers versus never-smokers was stronger among men with a
      body mass index less than 242 kg/m2 than among men with a body mass index of 24.2
      kg/m2 or more, although the absolute risk was greater in more obese men.
      CONCLUSION: The number of cigarettes smoked daily and the number of pack-years of
      exposure seem to be associated with development of impaired fasting glucose and
      type 2 diabetes in middle-aged Japanese men.

PMID- 10906833
TI  - Lactic acidosis and hepatic steatosis associated with use of stavudine: report of
      four cases.
AB  - BACKGROUND: An association between use of zidovudine and didanosine and a rare
      but life-threatening syndrome of hepatic steatosis, lactic acidosis, and myopathy
      has been reported. OBJECTIVE: To describe the syndrome of hepatic steatosis,
      lactic acidosis, and myopathy in four patients taking stavudine. DESIGN: Case
      series. SETTING: A community hospital in Washington, D.C., and National
      Institutes of Health Clinical Center, Bethesda, Maryland. PATIENTS: Two men and
      two women with HIV-1 infection who were taking stavudine presented with lactic
      acidosis and elevated levels of aminotransferases. All patients required
      intensive care. MEASUREMENTS: Levels of lactic acid, alanine aminotransferase,
      aspartate aminotransferase, amylase, and lipase; computed tomography of the
      abdomen; liver biopsy (two patients); and muscle biopsy (two patients). RESULTS:
      Histologic findings consistent with mitochondrial injury confirmed the diagnosis
      of hepatic or muscle abnormality. CONCLUSION: Because hepatic steatosis may be
      life-threatening, physicians should consider it as a possible cause of elevated
      hepatic aminotransferase levels among patients taking stavudine.

PMID- 10906835
TI  - Recertification in internal medicine: a program of continuous professional
      development. Task Force on Recertification.
AB  - In 2000, the American Board of Internal Medicine (ABIM) introduced a second
      generation recertification process that builds on the current knowledge-centered
      program by adding assessments of clinical and communication skills, clinical
      performance, and medical outcomes. The three-part process, called a program of
      continuous professional development, includes innovative self-evaluation
      exercises, documentation of essential knowledge, and confirmation of satisfactory
      qualifications and professional and community good standing. The program
      introduces the principles of continuous quality improvement; deemphasizes the
      summary nature of the traditional secure examination; and is designed to be a
      more continuous, less saltatory process for maintaining clinical competence. With
      the continuous professional development program, ABIM believes that it has taken
      a substantial step toward creating a recertification process that meets its goal
      of being valuable, doable, tolerable, and affordable" while maintaining the high
      standards expected of an accountable profession.

PMID- 10906834
TI  - The pathology of median neuropathy in acromegaly.
AB  - BACKGROUND: Median neuropathy is commonly associated with acromegaly, although
      its pathology is uncertain. OBJECTIVE: To study the pathology of median
      neuropathy in acromegaly by using magnetic resonance imaging (MRI). DESIGN: Case
      series. SETTINGS: Outpatient clinic and MRI unit. PATIENTS: Nine patients with
      acromegaly, four of whom had clinical symptoms of neuropathy. MEASUREMENTS: At
      presentation and 6 months after treatment, median nerve size, its signal
      intensity, and the volume of the carpal tunnel contents were measured. RESULTS:
      At presentation, patients with symptoms of neuropathy had increased nerve size
      and signal intensity compared with asymptomatic patients, but the two groups did
      not differ in volume of carpal tunnel contents. These measures improved with
      treatment of acromegaly in symptomatic patients; asymptomatic patients
      experienced no change or worsening. CONCLUSION: The predominant pathology of
      median neuropathy in acromegaly seems to be increased edema of the median nerve
      within the carpal tunnel rather than extrinsic compression from increased volume
      of the carpal tunnel contents.

PMID- 10906837
TI  - Trouble.

PMID- 10906836
TI  - Update in general internal medicine.

PMID- 10906838
TI  - Physician prescribing of sterile injection equipment to prevent HIV infection:
      time for action.
AB  - Injection drug users, their sex partners, and their children are at high risk for
      acquiring HIV infection and other bloodborne diseases. The risk for disease
      transmission in the United States is partly the result of restricted access to
      sterile injection equipment. Physicians and pharmacists can play an important
      role in providing syringe access by prescribing and dispensing syringes to
      patients who use injection drugs and cannot or will not enter drug treatment
      Prescribing and dispensing injection equipment are ethical, clinically
      appropriate, and fully consistent with current public health guidelines on
      disease prevention. An analysis of the laws of the 50 U.S. states, the District
      of Columbia, and Puerto Rico finds that physicians in nearly all these
      jurisdictions may legally prescribe sterile injection equipment to prevent
      disease transmission among drug-using patients and that pharmacists in most
      states have a clear or reasonable legal basis for filling the prescriptions.
      Given these medical and legal findings, physicians may wish to take a larger role
      in improving access to sterile injection equipment by prescribing this equipment
      for their patients where this practice is legal, and by joining efforts to change
      the law where it poses a barrier.

PMID- 10906839
TI  - The burning issue of chronic gastroesophageal reflux.

PMID- 10906840
TI  - News from the International Committee of Medical Journal Editors.

PMID- 10906841
TI  - Patient-doctor.

PMID- 10906842
TI  - Resuscitation.

PMID- 10906843
TI  - Chronic dizziness in older adults.

PMID- 10906844
TI  - Chronic dizziness in older adults.

PMID- 10906845
TI  - Sister (Mary) Joseph's nodule.

PMID- 10906846
TI  - Correction: Liver injury and rosiglitazone.

PMID- 10906847
TI  - Helping physicians to keep abreast of the medical literature: Medical and
      Philosophical Commentaries, 1773-1795.

PMID- 10906848
TI  - Endocarditis: A Multidisciplinary Approach to Modern Treatment.

PMID- 10906849
TI  - Cardiology 1999.

PMID- 10906850
TI  - The need and means for evidence-based medicine in developing countries.

PMID- 10906851
TI  - Fractures in children are different. 1976.

PMID- 10906852
TI  - Early management of the child with multiple injuries.
AB  - Resuscitation of the child with multiple injuries is similar to that for adults,
      except that instrumentation and therapy must be tailored in accordance with
      variable patient size, emotional maturity, and injury response. Because this
      response is rapid and often compensatory, there is greater reliance on
      noninvasive means to diagnose and manage the injured child. Children who suffer
      multisystem trauma typically present with head injury, followed in decreasing
      frequency by limb fracture and trauma to the torso. The timing of fracture
      fixation in a patient with multiple injuries remains controversial. In general,
      clinical judgment will determine the optimal timing for fracture reduction or
      operative fracture fixation. Management of an associated vascular injury must
      take into consideration the mechanism of injury, tissue viability, vessel size,
      and technical limitations. With appropriate initial resuscitation, careful
      monitoring, and sound clinical judgement, most injured children can be expected
      to have a good clinical outcome.

PMID- 10906853
TI  - Effect of interposed periosteum in an animal physeal fracture model.
AB  - To study the effect of interposed periosteum on physeal fracture healing, 52
      skeletally immature female Harlan Sprague-Dawley rats, 4 to 5 weeks of age, were
      randomized to one of three cohort groups. All animals underwent surgical
      dissection of the left proximal medial tibia; dissection consisted of superficial
      exposure and incision of a standard periosteal flap. Animals in Group I (fracture
      alone) underwent physeal fracture; those in Group II (fracture and periosteum)
      underwent physeal fracture with interposition of periosteum in the fracture site,
      and those in Group III (positive control) underwent physeal fracture, excision of
      1/2 of the growth plate, and interposition of periosteum in the defect. After
      histologic examination of serial sections, fracture alone resulted in physeal
      injury frequently associated with small bar formation without a reduction in leg
      length. With the addition of interposition of periosteum into the fracture site,
      a small, but statistically significant, increase in leg length discrepancy
      frequently associated with small histologic bar formation occurred when compared
      with fracture alone.

PMID- 10906854
TI  - Treatment of soft tissue defects in pediatric patients using the V.A.C. system.
AB  - Twenty-seven consecutive pediatric patients presenting to the orthopaedic surgery
      or plastic surgery services were reviewed after completion of wound care with the
      Vacuum Assisted Closure (V.A.C.) system. Each patient presented with complex soft
      tissue wounds requiring coverage procedures. Patients with acute wounds and
      wounds present after nonsuccessful attempts at surgical closure (dehisced
      incisions and failed flaps) were treated. All soft tissue defects healed without
      extensive coverage procedures using the V.A.C. system. In the majority of
      patients, use of the V.A.C. system produced a profuse bed of granulation tissue
      over all exposed bone, tendon, joint, and/or hardware, which could be covered
      with split thickness skin graft. Other patients were treated successfully with
      delayed primary closure, local flap advancement (one patient underwent a pedicled
      cross-leg flap), or by secondary intention. Use of the V.A.C. device is valuable
      in increasing the rate of granulation tissue formation and healing of extensive
      soft tissue injuries in pediatric patients. This vacuum system aids in the
      debridement of necrotic tissue and local soluble inflammatory mediators that may
      inhibit the proliferation of granulation tissue. These improvements in the local
      wound environment seem to accelerate wound healing compared with traditional
      methods. Before the development of the V.A.C. system, a minimum of nine patients
      within this group would have required free tissue transfer to obtain adequate
      coverage. The V.A.C. device seems to permit earlier coverage with local tissue or
      split-thickness skin grafting techniques, thereby decreasing the need for
      extensive microvascular tissue transfers in pediatric patients.

PMID- 10906855
TI  - Compartment syndrome in ipsilateral humerus and forearm fractures in children.
AB  - Ipsilateral fractures of the humerus and forearm are uncommon injuries in
      children. The incidence of compartment syndrome in association with these
      fractures is controversial. The authors reviewed 978 consecutive children
      admitted to the hospital with upper extremity long bone fractures during a 13
      year period. Forty-three children with ipsilateral fractures of the humerus and
      forearm were identified. Of 33 children with a supracondylar humerus fracture and
      ipsilateral forearm fracture, three children (7%) had compartment syndrome
      develop and required forearm fasciotomies. All three cases of compartment
      syndrome occurred among nine children with ipsilateral displaced extension
      supracondylar humerus and displaced forearm fractures; the incidence of
      compartment syndrome was 33% in this group. These findings suggest that children
      who sustain a displaced extension supracondylar humerus fracture and displaced
      forearm fracture are at significant risk for compartment syndrome. These children
      should be monitored closely during the perioperative period for signs and
      symptoms of increasing intracompartmental pressures in the forearm.

PMID- 10906856
TI  - Intramedullary Steinmann pin fixation of forearm fractures in children. Long-term
      results.
AB  - The current study is a retrospective clinical and radiographic review of all
      children treated with intramedullary Steinmann pins for fixation of diaphyseal
      forearm fractures at one institution. Thirty patients were reviewed. Twenty-five
      patients had fractures of both bones, three had Monteggia fracture-dislocations,
      and two had isolated radial fractures. Eight fractures were open. The average age
      of the patients at the time of surgery was 9 years 3 months (range, 4 years 1
      month-14 years 3 months). Time to union averaged 6 weeks but a slightly longer
      healing time was seen in patients older than 10 years of age. Subjective,
      objective, and radiographic evaluation at 3 years 6 months average followup
      revealed no significant side to side differences. There were six complications
      (two pin site infections, two cases of fracture displacement after pin removal,
      one extensor pollicus longus tendon rupture requiring repair, and one
      refracture), none of which affected outcome at followup. When combined with an
      open reduction, one intramedullary Steinmann pin provides adequate stability in
      most diaphyseal forearm fractures in children with excellent results and few
      complications.

PMID- 10906857
TI  - Supracondylar humerus fractures in children. Comparison of operative treatment
      methods.
AB  - A retrospective analysis was performed of 87 children treated operatively for
      supracondylar humerus fractures by 18 different surgeons during a 6-year period.
      No patient suffered from compartment syndrome or Volkmann's ischemic contracture.
      Early postoperative fracture displacement occurred in four (7%) of 60 patients
      with Type III fractures, and in one (4%) of 23 patients with Type II fractures.
      Displacement occurred in one (2%) of 52 Type III fractures stabilized with
      crossed medial and lateral Kirschner wires, whereas displacement occurred in two
      (28%) of seven Type III fractures stabilized with lateral wires only. Thirty-four
      patients could be located for long-term followup; complete examination of both
      upper extremities was performed on these 34 patients at an average of 33 months
      postoperatively. The long-term results were excellent in 19 (56%), good in seven
      (21%), fair in one (3%), and poor in seven (21%) patients. Five additional
      patients were not available for followup at the time of the current study, but
      had followup of at least 6 months available. Of the 39 patients with followup of
      at least 6 months, five patients' fractures (13%) healed with coronal plane
      malalignment greater than 10 degrees which resulted in gunstock deformity. There
      was no statistically significant relationship between treatment method and
      gunstock deformity. However, none of the patients with gunstock deformity had
      compromised activity because of the deformity, and all had full elbow extension
      and at least 130 degrees elbow flexion.

PMID- 10906858
TI  - Crossed pin fixation of displaced supracondylar humerus fractures in children.
AB  - The results of 42 children with displaced supracondylar fractures of the humerus
      (six Gartland Type II and 36 Gartland Type III) treated with crossed pin fixation
      are reported. In 37 fractures (88%) the teardrop configuration was restored
      successfully. All fractures healed without loss of reduction. No patients had
      iatrogenic ulnar nerve injury. Crossed-pin fixation of supracondylar humeral
      fractures is a safe and effective way of maintaining skeletal stability in
      children. Careful technique safeguards against ulnar nerve injury.

PMID- 10906859
TI  - Neurovascular injuries in type III humeral supracondylar fractures in children.
AB  - Clinical and radiographic records of 210 consecutive children treated for Type
      III extension humeral supracondylar fractures during a 66-month period were
      reviewed retrospectively to determine (1) the incidence of neural and vascular
      injuries associated with this fracture; (2) the frequency of the type of nerve
      injured; and (3) the relationship of fracture displacement to neural and vascular
      compromise. Forty patients (19.1%) had neural compromise, vascular compromise, or
      both. Nerve injuries occurred in 13.3% of patients, combined nerve and vascular
      compromise occurred in 2.9%, and vascular compromise occurred in 2.9% of
      patients. Median nerve injuries accounted for 58.9% of nerve injuries followed by
      radial (26.4%) and ulnar (14.7%) lesions. Eighty percent of the median nerve
      injuries involved the anterior interosseous nerve. Posterolateral fracture
      displacement was correlated with median nerve and vascular compromise.
      Posteromedial fracture displacement strongly correlated with radial nerve injury.
      Recognition of fracture displacement pattern provides a guide to clinical
      examination to assess associated neural injury, in particular, the anterior
      interosseous nerve, which may be difficult to evaluate in a child who is
      uncooperative.

PMID- 10906860
TI  - Traumatic hip dislocation in children. Long-term followup of 42 patients.
AB  - To assess the impact of traumatic hip dislocations in the skeletally immature
      patient, 42 children younger than 16 years of age (average age, 9 years 10
      months) who were treated at the authors' institution were studied. Data were
      collected from charts and radiographs and by completion of questionnaires. The
      average followup after injury was 10 years 1 month. The majority of dislocations
      (64%) were attributable to low energy injuries. Ipsilateral fractures about the
      hip occurred in 17% of patients. Avascular necrosis of the femoral head developed
      in 12% of patients, with the amount of time spent dislocated being the only
      statistically proven risk factor. Patients whose reduction was delayed greater
      than 6 hours had a 20 times higher risk of having avascular necrosis develop
      compared with patients whose hips were reduced in 6 hours or less. The use of
      computed tomography for joint asymmetry of 3 mm or greater and omission of bone
      scan screening were supported by this study. Functional outcomes were very good
      in this series with 95% of patients suffering mild (usually weather related) or
      no pain and 95% of patients suffering mild pain (intermittently noticeable) or no
      limp. A large percentage of the patients (78%) continued to participate in high
      demand activities such as football, soccer, and basketball.

PMID- 10906861
TI  - Acetabular fractures in children and adolescents.
AB  - A retrospective study of 29 acetabular fractures in children 2 to 16 years of age
      with an average followup of 14 years is presented. Nineteen patients had an
      additional dislocation of the femoral head and 14 patients had an associated
      neurologic injury. Surgical treatment was performed in 16 patients and consisted
      of open reduction and internal fixation in 14 patients and a simple arthrotomy in
      two patients. Thirteen patients were treated nonoperatively with traction or
      bedrest. The outcome was satisfactory in all patients with undisplaced fractures
      and fractures with disruption of a small fragment. Eight patients with linear
      fractures with instability all were treated surgically. All but one of the
      patients had a satisfactory functional outcome; one patient had early
      degenerative changes develop after an open pelvic and acetabular fracture.
      Patients with central fractures and dislocations had a relatively poor outcome,
      and congruency was achieved in only one of the four patients who were treated
      surgically. Results may deteriorate with time, as was seen when the results of
      the current study were compared with those published 10 years previously.

PMID- 10906862
TI  - Disruption of the pelvic ring in pediatric patients.
AB  - Pelvic ring disruptions are rare in children. Generally, nonoperative treatment
      has been recommended for children with these injuries. The authors
      retrospectively reviewed the medical records and radiographs of 189 patients with
      pelvic ring disruptions who were evaluated at a tertiary care children's hospital
      during a 10-year period. Of the 189 patients, 57 were identified with unstable
      pelvic fractures. These fractures were classified according to Tile, and Torode
      and Zieg. Forty-three of these patients were available to complete a subjective
      evaluation of their treatment at midterm followup. Thirteen patients were treated
      operatively and 30 were treated nonoperatively. There was no significant
      difference in subjective scoring between the two groups for pain at rest, pain
      with activity, limp, leg length discrepancy, and overall satisfaction with
      treatment. Overall, there were 92% good or excellent results in the patients who
      were treated operatively and 80% good or excellent results in the patients who
      were treated nonoperatively. Patients in both groups reported a high level of
      satisfaction with their outcome regardless of their fracture classification and
      treatment method.

PMID- 10906863
TI  - Accidental and nonaccidental femur fractures in children.
AB  - A retrospective review of 207 patients younger than 6 years of age who sustained
      nonpathologic diaphyseal femur fractures was done, which emphasized the
      characteristics of accidental versus nonaccidental injury. There were 214
      fractures in 123 boys and 83 girls (the gender of one patient was unknown). The
      average age of the patients was 2.73 years. Mechanisms of injury were pedestrian
      struck by a car (62 patients), falls (92 patients), and motor vehicle accidents
      (10 patients). Nineteen patients did not have a history of trauma. Seventy-six
      cases were investigated for child abuse. The results of 13 investigations were
      positive. Overall, the morphologic features of the fractures were transverse
      (38%), spiral (27%), and oblique (17%). In the investigated group, 27% of the
      fractures were transverse, 39% were spiral, and 15% were oblique. In those cases
      with positive results of the investigation, 36% of the fractures were transverse,
      36% were spiral, and 7% were oblique. Although transverse fractures are most
      common in accidental and nonaccidental injuries, many practitioners think spiral
      fractures are pathognomonic of abuse. The current data show that although spiral
      fractures were less common than transverse fractures overall, and no more common
      in the cohort of patients in whom the results of the child abuse investigations
      were positive, they were overrepresented in the cohort that was investigated.
      This suggests that spiral fractures are viewed as particularly suspicious, which
      may lead to missed cases of nonaccidental injury in children with transverse
      fractures.

PMID- 10906864
TI  - Immediate hip spica casting for femur fractures in pediatric patients. A review
      of 175 patients.
AB  - Immediate closed reduction and application of a well-molded hip spica cast is a
      safe and effective treatment option for closed, isolated femur fractures in
      children who weigh between 10 and 100 pounds. Between 1988 and 1996, 190
      immediate hip spica casts were placed on children with isolated femoral shaft
      fractures who weight between 10 and 100 pounds. Fifteen patients were lost to
      followup leaving 175 children who were evaluated and followed up for at least 2
      years after the hip spica cast was removed (range 2-10 years). The femur
      fractures were reduced closed and placed in a 1 1/2 hip spica cast in the
      emergency room with the patient under conscious sedation or in the operating room
      with the patient under general anesthesia. All of the children returned home
      within 24 hours of the procedure. All 175 femur fractures united within 8 weeks.
      The only complication was a refracture in a 25 pound child who fell 1 week after
      the cast was removed. No significant residual angular deformities were present in
      any of the children at last followup. None of the children required external shoe
      lifts, epiphysiodesis, antibiotics, irrigation and debridements, or limb
      lengthening procedures for leg length inequalities. The authors think that
      immediate closed reduction and placement of a well-molded hip spica cast is a
      safe and reliable treatment option for isolated, closed femur fractures in
      children from birth to 10 years of age who weigh less than 80 pounds.

PMID- 10906865
TI  - Intramedullary nailing of femoral shaft fractures in children via the trochanter
      tip.
AB  - Closed rigid intramedullary nailing of femoral shaft fractures in children has
      been associated with avascular necrosis of the femoral head. Avascular necrosis
      of the femoral head is thought to result from damage to the medial femoral
      circumflex artery by placing the nail through the piriformis fossa. The authors
      describe the early results of a technique in which the nail is placed through the
      tip of the greater trochanter, thus avoiding the piriformis fossa and possible
      damage to the medial circumflex artery. Between 1988 and 1995, the authors
      performed this procedure on 34 patients, who ranged in age from 10 years 2 months
      to 17 years 6 months. Followup time ranged from 1 month to 120 months. There were
      no infections, nonunions, rotational deformities, or implant failures. Twenty
      patients with open physes had a followup of 2 years or more. To date, no patient
      had avascular necrosis of the femoral head develop. The trochanteric tip entry
      point is recommended for closed rigid intramedullary nailing of femoral shaft
      fractures in children and adolescents.

PMID- 10906866
TI  - Ender rod fixation of femoral shaft fractures in children.
AB  - Ender rod fixation for femoral shaft fractures in children was evaluated in a
      prospective study at two Level 1 trauma centers. Fifty-seven fractures in 52
      patients were evaluated. Criteria for inclusion in the study included age younger
      than 14 years, femoral shaft fractures occurring in the middle 3/5, canal size
      greater than 7 mm, and parental consent. Hip and knee motion, gait, leg length
      discrepancy, and rotational asymmetry were evaluated by clinical examination.
      Standard radiographs were used to measure any residual angulation. A subset of
      patients whose injuries occurred more than 12 months previously was evaluated
      using scanograms. Followup averaged 20 months. There were no delayed unions and
      all fractures healed within 12 weeks. Clinically significant leg length
      discrepancy, malunion, or loss of motion did not occur. Functional results were
      excellent and complications were minor. Ender rod fixation of femur fractures in
      children allows the advantages of surgical fixation with minimal risk of
      complications.

PMID- 10906868
TI  - Percutaneous release of the common extensor origin for tennis elbow.
AB  - Thirty patients (32 elbows) who had surgery for tennis elbow were examined.
      Symptoms were present an average of 18 months before surgery. The operation was
      done percutaneously through an incision just distal to the lateral epicondyle,
      through which the common extensor origin was released. The followup period was 6
      to 61 months, with an average of 26 months. Twenty-nine elbows had good or
      excellent results. In these 29, the pain was relieved an average of 9 weeks after
      surgery. Three elbows did not improve significantly, and treatment was considered
      a failure. The grip strength improved from an average of 60% of the opposite side
      before surgery to 90% after surgery.

PMID- 10906867
TI  - The floating knee in the pediatric patient. Nonoperative versus operative
      stabilization.
AB  - The results of nonoperative and operative or rigid stabilization of ipsilateral
      femur and tibia fractures in children and adolescents were evaluated. Twenty-nine
      consecutive patients with open physes (30 affected extremities) were reviewed.
      Their mean followup was 8.6 years (range, 1.1-18.6 years). The nonoperative group
      consisted of 16 patients and 16 extremities treated by skeletal traction of the
      femoral fracture, closed reduction and splinting or casting of the tibia
      fractures, and eventual immobilization in a hip spica cast. The operative group,
      was comprised of 13 patients and 14 extremities in which one or both fractures
      were treated by open reduction and internal fixation, intramedullary fixation, or
      external fixation. Despite higher modified injury severity scores and skeletal
      injury scores, the patients who were treated operatively had a significantly
      reduced hospital stay, 20.1 days versus 34.9 days, respectively; decreased time
      to unsupported weightbearing, 16.8 weeks compared with 22.3 weeks, respectively;
      and fewer complications. Operative stabilization of the femur had a significant
      effect on decreasing the length of hospital stay and the time to unassisted
      weightbearing. The patients also were analyzed according to their age at the time
      of injury: 9 years of age or younger and 10 years of age and older. The younger
      children who were treated nonoperatively had an increased rate of lower extremity
      length discrepancy, angular malunion, and need for a secondary surgical procedure
      as compared with younger children who were treated operatively with rigid
      fixation. Based on the results of the current study, operative stabilization of
      at least the femur fracture and, preferably, both fractures in the treatment of a
      child with a floating knee is recommended, even for younger children.

PMID- 10906869
TI  - Endoscopic carpal tunnel release in patients receiving long-term hemodialysis.
AB  - This study evaluated the clinical results of endoscopic carpal tunnel release in
      carpal tunnel syndrome caused by long-term hemodialysis and compared the results
      with that of idiopathic carpal tunnel syndrome. Operations were done in 32
      patients (60 hands) with idiopathic carpal tunnel syndrome and in eight patients
      (15 hands) with carpal tunnel syndrome resulting from long-term hemodialysis.
      There was no significant difference in findings of preoperative evaluations and
      postoperative clinical results between the two groups, except for a difference
      with the patient satisfaction score with surgery on a visual analogue scale. The
      mean satisfaction score was 9.0 at 6 months, 9.3 at 1 year, and 9.5 at the 2-year
      followup in the group of patients with idiopathic carpal tunnel syndrome.
      However, in the group of patients with carpal tunnel syndrome resulting from long
      term hemodialysis, the mean satisfaction score was 8.5 at 6 months, 8.2 at 1
      year, and 6.5 at the 2-year followup. The score began to decrease at an average
      of 17.2 months after surgery. Long-term hemodialysis related carpal tunnel
      syndrome showed satisfactory short-term clinical results until approximately 1.5
      years after the operation. After that time, the symptoms tended to deteriorate in
      50% of the patients who received hemodialysis continuously.

PMID- 10906870
TI  - Cementless acetabular replacement in the young. A 5- to 10-year prospective
      study.
AB  - This article presents a prospective clinical and radiologic review of 55 total
      hip replacements in 50 patients in which the cementless Harris-Galante porous
      coated acetabular component was used. All patients were 50 years of age or
      younger. The cups were inserted by 15 different surgeons. The minimum followup
      was 5 years, with a mean of 7 years. No acetabular component has been revised for
      loosening, and none have migrated. Three (5.5%) cups have progressive bone
      component radiolucent lines, two (3.6%) of which are complete. Six (10.9%)
      acetabular liners have been replaced for excessive polyethylene wear, and an
      additional four (7.3%) show sufficient wear to produce obvious radiographic
      eccentricity of the femoral head. All of the revised liners had 32-mm femoral
      heads and an initial polyethylene thickness of less than 6 mm. Although the
      results reflect excellent fixation of this component in the medium term, the
      incidence of exchange of the polyethylene liner for excessive wear is
      unacceptably high. The reduction in polyethylene thickness associated with the
      use of a metal-backed component and a 32-mm articulation was one of the factors
      contributing to the accelerated wear patterns seen in this series.

PMID- 10906871
TI  - Is the preoperative radiograph useful in predicting the outcome of a total hip
      replacement?
AB  - The preoperative radiographs of 1015 patients undergoing 1163 total hip
      replacements for osteoarthritis were evaluated to determine if a relationship
      exists between the extent of osteoarthritis and the clinical results of a total
      hip replacement. Preoperative radiographs were graded with respect to the degree
      of cartilage space loss, direction of cartilage space loss (femoral head
      migration), and severity of osteophyte formation. Followup averaged 32.1 months
      (range, 6-93 months). Greater degrees of cartilage space loss correlated with
      lower hip scores preoperatively but were unrelated to preoperative pain. These
      patients had statistically less pain at 6 months and 1 year. Patients with
      superior cartilage space loss before surgery also had statistically less pain at
      6 months. However, at 3 years and beyond, pain was independent of degree of
      preoperative cartilage space loss, osteophyte formation, or femoral head
      migration. In addition, hip scores at any followup were independent of the degree
      of osteoarthritis observed on the preoperative radiograph. These findings provide
      statistical support to the concept that greater degrees of joint space loss
      correlate with better relief of pain and less severe joint space loss correlates
      with less relief of pain within the first year after total hip replacement. At 3
      years and beyond, hip and pain scores were independent of the degree of
      preoperative osteoarthritis.

PMID- 10906872
TI  - Effect of resin type and manufacturing method on wear of polyethylene tibial
      components.
AB  - The purpose of this study was to examine the effect of ultrahigh molecular weight
      polyethylene resin type and manufacturing method on wear of Miller-Galante I and
      II tibial knee components. Thirteen Miller-Galante I and 10 Miller-Galante II
      components were retrieved at revision surgery. The Miller-Galante I tibial
      components were made by direct compression molding of Hi-fax 1900 resin and the
      Miller-Galante II tibial components were made by machining from ram extruded rod
      of GUR 415 resin. Both generations were gamma radiation sterilized in air. The
      Miller-Galante I retrievals had significantly more wear damage in the form of
      scratching and embedded metallic debris, whereas the Miller-Galante II retrievals
      had significantly more wear damage in the form of delamination. For the implants
      with an implantation time of 5 years or more, the Miller-Galante II polyethylene
      had a significantly greater maximum density value than did the Miller-Galante I
      polyethylene. Examination of thin sections of the Miller-Galante II components
      revealed that delamination occurred through a subsurface region of severely
      oxidatively degraded polyethylene; no such subsurface degraded region was
      observed for the Miller-Galante I components. The results of this study suggest
      that delamination of polyethylene tibial components that have been gamma
      radiation sterilized (in air) is influenced by resin type or manufacturing method
      or both.

PMID- 10906873
TI  - Distribution of neuropeptides in synovium of the knee with osteoarthritis.
AB  - Synovial tissue was obtained from medial, lateral, and suprapatellar sites of 21
      knees (15 patients) with medial compartmental osteoarthritis at surgery. All
      patients reported pain around the medial joint of their knees while walking and
      climbing stairs. For investigation of the synovial innervation, six samples were
      stained with modified gold chloride and the others with an immunohistochemical
      method using antisera against neuropeptides. The extent of synovitis in each part
      was scored using a new 10-point scale. The results showed that the synovium had
      an extensive neural network in the somatic and autonomic nervous systems.
      Neuropeptides were most abundant, with an especially large number of substance P
      and calcitonin gene related peptide immunoreactive free nerve endings. Some of
      the substance P positive nerve endings were surrounded by monocytes. Substance P
      and calcitonin gene related peptide were found more frequently in the medial than
      in the lateral or suprapatellar areas. Substance P positive free nerve endings
      showed more dendritic morphologic features in the medial region than did those in
      the lateral and suprapatellar regions, and small nerves were accompanied by newly
      developed vessels in synovial villi. In the medial region, the synovitis was more
      remarkable than in the lateral region. These findings suggest that free nerve
      endings containing substance P may modulate inflammation and the pain pathway in
      osteoarthritis.

PMID- 10906874
TI  - Correction of hallux valgus. Metatarsal osteotomy versus excision arthroplasty.
AB  - The long-term retrospective results (followup range, 10-22 years) of an
      uncontrolled series of basal metatarsal closing wedge osteotomies and Keller's
      excision arthroplasties performed in patients 14 to 40 years of age are analyzed.
      In the osteotomy group, 34 patients (50 feet) were available for clinical review
      and 26 patients (37 feet) were available for radiologic review. In the Keller
      group, 24 patients (37 feet) were reviewed clinically and 23 patients (34 feet)
      were reviewed radiologically. Patients were assessed using the Hallux
      Metatarsophalangeal Interphalangeal Scale of the American Foot and Ankle Society,
      an additional clinical score, weightbearing radiographs, the patient's record,
      and clinical investigation. Statistical analysis revealed significantly better
      results of the clinical and radiologic outcomes after osteotomy. In the osteotomy
      group, the first metatarsal was elevated dorsally in 14 feet (38%). The incidence
      of varus deformities was higher with basal osteotomy (18% versus 5.4%).
      Metatarsalgia occurred similarly in both groups (28% versus 27%). It is known
      that these techniques should be applied to different patient populations.
      However, they formerly were used for the same indication. This long-term analysis
      shows that the Keller arthroplasty should be abandoned for the treatment of
      hallux valgus in young and active patients. The basal metatarsal closing wedge
      osteotomy is conceptually the correct treatment for hallux valgus deformity for
      the younger patient; nevertheless, it is technically demanding and is associated
      with a higher risk of failure. The long-term results of both procedures are
      unacceptable for the patient and the surgeon. The short and middle-term results
      of the newer basal type osteotomies, such as the proximal crescentic osteotomy,
      the proximal chevron osteotomy, or the proximal oblique osteotomy combined with
      distal soft tissue releases, suggest a more satisfying long-term outcome.

PMID- 10906875
TI  - Treatment of myxoid liposarcoma in pregnancy.
AB  - Two cases of pregnancy associated with myxoid liposarcoma are presented. Both
      patients were treated with hyperthermoradiotherapy after the induced delivery of
      healthy infants and by surgical excision of the tumor 5 to 7 weeks after
      delivery. No local recurrence or distant metastasis occurred; the children have
      progressed normally for 4 and 5 years, respectively, after surgery. Because
      coexistence of pregnancy and sarcoma is rare, it is difficult for the clinician
      to develop an appropriate approach to the management of bone and soft tissue
      sarcoma during pregnancy. The literature was reviewed regarding the effect that
      pregnancy may have on the clinical behavior of sarcoma and the effect treatment
      for sarcoma may have on the fetus.

PMID- 10906877
TI  - Malignant schwannoma of the digital nerve in a child. A case report.
AB  - An extremely rare case of malignant schwannoma (malignant peripheral nerve sheath
      tumor) arising in the digital nerve in the right ring finger of a child is
      described. The patient was an 8-year-old boy who did not have neurofibromatosis
      (von Recklinghausen's disease). He noticed a small tender mass on the tip of his
      right ring finger in 1991. The lesion was excised twice. However, the tumor
      recurred soon after each surgery. Histologic examination revealed malignant
      schwannoma. He eventually underwent disarticulation of the ring finger at the
      metacarpophalangeal joint in 1995. There was no recurrence or distant metastasis
      at followup in July 1999. Solitary malignant schwannomas can occur in the small
      peripheral nerves and in the major nerves.

PMID- 10906876
TI  - Tumor volume change as a predictor of chemotherapeutic response in osteosarcoma.
AB  - The change in osteosarcoma tumor volume after preoperative adjuvant chemotherapy
      and its relationship to the histopathologic response was investigated using
      various reproducible volumetric methods. Tumor volume was measured before and
      after chemotherapy in 41 patients with osteosarcoma using an ellipsoid formula in
      plain radiography and magnetic resonance imaging and three-dimensional magnetic
      resonance imaging measurement. Based on intraobserver and interobserver
      variability for the volumetric measurements of each method, three-dimensional
      magnetic resonance imaging measurement was the most reproducible. In three
      dimensional magnetic resonance measurements, the correlation of the
      histopathologic response with absolute and relative total tumor volume changes
      and extraosseous volume change were significant. The good responder group showed
      a greater reduction in tumor volume after chemotherapy, although there was no
      significant difference in pretreatment tumor volume between the good and poor
      responder groups. The group with a decreased or stable tumor volume represented a
      good histopathologic response with a sensitivity of 85%, specificity of 76%, and
      positive predictive value of 88%. The change in tumor volume of osteosarcoma
      measured by three-dimensional magnetic resonance imaging could predict
      histopathologic response after three cycles of neoadjuvant chemotherapy.

PMID- 10906878
TI  - Orthopaedic manifestations of Ehlers-Danlos syndrome.
AB  - Ehlers-Danlos syndrome is the most prevalent heritable disorder of connective
      tissue. Musculoskeletal problems include joint pain, swelling and instability,
      and spinal deformity. This study was undertaken to assess functional orthopaedic
      problems of patients with Ehlers-Danlos syndrome. Sixty patients with genetically
      verified Ehlers-Danlos syndrome (range, 8-60 years; mean, 34 years) who attended
      a National Ehlers-Danlos Syndrome Foundation learning conference were evaluated
      by questionnaire, clinical examination, and when indicated, radiographs. A
      database of 250 items per patient was constructed and statistically assessed
      using analysis of variance. Because of rarity of Types VII and VIII, these two
      patients were dropped from the analysis. Fifty-eight patients had Ehlers-Danlos
      syndrome Types I, II, III, or IV and form the study cohort. Among these four
      types, there were no significant differences in history of joint dislocation,
      swelling, or types of orthopaedic surgical procedures experienced. Thirty
      patients with Type III Ehlers-Danlos syndrome reported joint pain more frequently
      than did patients with Types I, II, or IV. Ambulation was impaired significantly
      in patients with Type III disorder as a whole, as was functional hand strength
      and upper extremity function. Back or neck pain was a common (67.2%) report among
      patients with all types of disease but did not correlate with the presence or
      absence of spinal deformity. Contrary to most previous reports, the patients in
      this study showed that Type III Ehlers-Danlos syndrome was the most debilitating
      form with respect to musculoskeletal function.

PMID- 10906879
TI  - Proximal femoral fracture. Range of hip motion as a predictor of fracture type.
AB  - A cadaveric study has shown that the femoral neck impinges on the posterior part
      of the acetabulum at an average of 54.5 degrees external rotation and that an
      intracapsular fracture can be reproduced by an impact load onto the greater
      trochanter with the hip in external rotation. A clinical study of hip rotation of
      the contralateral uninjured hip in 100 patients after proximal femoral fracture
      was done to compare the degree of external rotation between extracapsular and
      intracapsular fracture. The mean value for intracapsular fracture was 62.1
      degrees and for extracapsular fracture was 48.9 degrees. A retrieval study of the
      femoral head and neck from patients undergoing hip hemiarthroplasty for
      intracapsular fracture showed a consistent pattern of fracture with posterior
      comminution suggesting neck impingement. Previous work has suggested that an
      intracapsular fracture occurs during a fall when external hip rotation thrusts
      the femoral neck against the posterior margin of the acetabulum. The current
      investigation would support this hypothesis and suggests that the natural degree
      of external hip rotation is a predictor of fracture type.

PMID- 10906880
TI  - Distal radioulnar instability is an independent worsening factor in distal radial
      fractures.
AB  - Distal radial fractures in patients who are younger than the age when
      osteoporosis usually develops are different from fractures in the elderly.
      Arthroscopy has revealed these fractures often have a complex pattern of fracture
      related chondral and ligament injuries in the wrist. In Lund, Sweden, of the 92
      distal radial fractures that occurred during 1 year in patients younger than the
      age when osteoporosis usually develops, 76 patients were assessed after more than
      1 year (range, 14-38 months). The examination included questions, a visual
      analogue scale for pain, a physical examination, bilateral radiographic
      assessment, and wrist score determination according to Gartland and Werley.
      Instability at clinical examination of the distal radioulnar joint was associated
      with a worse wrist score and doubled the visual analogue measures for pain at
      rest and pain at load. This instability was not correlated to any radiographic
      variable at the time of fracture or at followup. The distal radioulnar joint was
      painful in 17 of the 27 patients with instability. Radiographic scapholunate
      dissociation did not affect the outcome. However, radiographic osteoarthrosis
      Grade 1 was associated with a worse wrist score. The outcome was dependent on the
      stability of the distal radioulnar joint, which in turn was not correlated to any
      radiographic parameter. Thus, destabilizing ligamentous injuries are thought to
      be an important cause of residual problems.

PMID- 10906881
TI  - Anatomy of the anterior sacroiliac joint with reference to lumbosacral nerves.
AB  - There are no detailed descriptions of the neural structures that may be seen
      during surgical interventions of the pelvis. Anatomic dissections were performed
      to see which nerves are endangered in approaches to the anterior sacroiliac joint
      for plate fixations. Sixty cadavers were dissected bilaterally. Fifty-one were
      male and nine were female. L4 and L5 nerve roots were followed along the
      sacroiliac joint from the intervertebral foramen to the entrance into the lesser
      pelvis. Measurements were made between the nerves and sacroiliac joint from the
      proximal end of the joint to the pelvic brim. The L4 nerve root and the
      lumbosacral trunk (and not the L5 nerve root) were the nerves most susceptible to
      injury because of their course and proximity to the sacroiliac joint. As a
      result, during the anterior approach and fixation of the sacroiliac joint with
      plates, extreme care should be taken to identify the L4 nerve root or lumbosacral
      trunk or both at the anteroinferior third of the joint because the distance
      between the nerve and the joint is less than 1 cm.

PMID- 10906882
TI  - Posterior interosseous nerve terminal branches.
AB  - Thirty upper limbs from skeletally mature embalmed cadavers were studied to
      define the most common pattern of the terminal branches of the posterior
      interosseous nerve. At 0.43 +/- 0.52 cm from the distal edge of the superficial
      head of the supinator and 8 +/- 1.6 cm from the lateral epicondyle, the posterior
      interosseous nerve branches, forming a common leash. There were six branches,
      which were arranged from the ulnar to the radial side at their origin from the
      common leash. The first and second branches supplied the extensor digitorum
      communis, the third branch supplied the extensor carpi ulnaris, the fourth branch
      supplied the extensor digiti minimi, and the fifth branch arose from the
      undersurface of the common leash and divided into two branches (medial and
      lateral) at 10.1 +/- 3.2 cm distal to the lateral epicondyle and 12.8 +/- 2.2 cm
      proximal to Lister's tubercle. The medial branch supplied the extensor pollicis
      longus and extensor indicis proprius. The lateral branch supplied the extensor
      pollicis longus and extensor pollicis brevis and ended at the wrist capsule. The
      sixth branch arose from the radial side of the common leash and divided into
      three branches. The first branch supplied the abductor pollicis longus and
      extensor pollicis brevis. The second branch supplied the abductor pollicis
      longus. The third branch supplied the superficial head of the supinator. The
      authors of this study describe the most efficient way to identify the six
      branches and how to avoid the risk of damaging them during surgical exposure.

PMID- 10906883
TI  - Changes in canine peripheral nerves during experimental callus distraction.
AB  - In 24 beagles, lengthening of the right tibia was performed by callus distraction
      after osteotomy and application of a ring fixator. Distraction was started the
      fifth day after surgery with a distraction rate of 0.5 mm twice per day and ended
      after 25 days. A control group of six additional dogs underwent tibial osteotomy
      and external fixation without distraction. Twelve animals with leg lengthening
      and three animals without leg lengthening were sacrificed immediately after the
      distraction period of 25 days (Group A), the remaining 15 dogs were sacrificed
      after an additional consolidation phase of another 25 days (Group B). From the
      distracted right leg and from the left control side of each animal, the tibial
      and peroneal nerves were removed and studied by means of morphometric analysis of
      semithin sections and electron microscopic study. The authors reported only minor
      alterations of the myelinated nerve fibers consisting in relatively thin
      myelinated remyelinating nerve fibers, single axon degeneration, or macrophages.
      There was no axonal sprouting. In contrast, electron microscopic study disclosed
      signs of late Wallerian degeneration and axonal regeneration of the nonmyelinated
      axons. Morphometric analysis of the peroneal nerves revealed a significant
      increase of fiber density and a reduced mean axon and fiber diameter in the
      consolidation period (Group B). Similar changes were found in the tibial nerves
      in Group A and disappeared in the consolidation phase (Group B). These features
      indicate that callus distraction leads to moderate degenerative changes, followed
      by repair mechanisms, almost complete recovery, and some nerve fiber growth.

PMID- 10906885
TI  - Graft healing in the bone tunnel in anterior cruciate ligament reconstruction.
AB  - The histologic sequence in the bone tunnel after anterior cruciate ligament
      reconstruction using the bone-patellar tendon-bone graft was investigated in this
      study. Eighteen adult mongrel dogs were used. After excision of the anterior
      cruciate ligament, the graft was routed through the bone tunnels and fixed with
      interference fit screws. After the dogs were sacrificed at intervals, the bone
      blocks containing the bone tunnels were isolated and processed for histologic
      examination. At the bone-bone interface, incorporation of the bone plug at each
      end of the graft was completed at 12 weeks. The structure of the tendon insertion
      of the grafted patellar tendon, consisting of four distinct zones, was observed
      without apparent necrotic and degenerative change for as long as 12 weeks.
      Between the tendon and the bone tunnel, a layer of hypercellular fibrous tissue
      gradually became mature with time. Thus, it appeared the morphologic
      characteristics and location of the reestablished attachment of the bone-patellar
      tendon-bone graft were more similar to those of the native anterior cruciate
      ligament compared with the graft to bone healing in the hamstring tendon graft.

PMID- 10906884
TI  - Role of leukocytes in radicular pain secondary to herniated nucleus pulposus.
AB  - Some studies have assessed inflammatory cells such as macrophages, lymphocytes,
      and neutrophils in herniated lumbar disc tissues using histologic analysis.
      However, there is no consensus regarding the relationships between clinical
      symptoms, including radicular pain and the presence of inflammatory cells. It has
      been shown that autologous nucleus pulposus relocated on the lumbar nerve root in
      rats produces time dependent and reversible mechanical hyperalgesia, which is
      thought to be a pain related behavior in peripheral neuropathic pain models. The
      purpose of this study was to determine whether leukocytes play a role in the
      mechanical hyperalgesia induced by the nucleus pulposus and to characterize the
      role of leukocytes in radicular pain attributable to lumbar disc herniation.
      Nitrogen mustard was used to induce and evaluate leukocytopenia in rats.
      Sensitivity to mechanical noxious stimuli was measured quantitatively, and
      inflammatory cells in granulation tissue around the nerve root were examined
      histologically. The nucleus pulposus produced neither mechanical hyperalgesia nor
      abundant inflammatory cells in rats with nitrogen mustard induced leukocytopenia.
      Neuropathic pain produced by the nucleus pulposus, when placed on the nerve root,
      may be related to inflammatory cell infiltration induced by relocation of the
      nucleus pulposus, rather than the nucleus pulposus itself.

PMID- 10906886
TI  - Arm mass in an 11-year-old boy.

PMID- 10906888
TI  - Making room for driver error?

PMID- 10906887
TI  - Marshall Urist Award. Interstitial collagenase gene expression correlates with in
      vitro invasion in human chondrosarcoma.
AB  - Matrix metalloproteinases contribute to the processes of local invasion and
      metastasis by providing cells with the ability to traverse tissue boundaries. The
      levels of gene expression were quantitated for matrix metalloproteinases-1 and
      tissue inhibitors of metalloproteinases-1 in human chondrosarcoma cell lines, and
      the results were correlated with cell differentiation, collagenase activity, and
      in vitro invasion. Three well characterized human cell lines were used in this
      study, with the level of chondrocytic differentiation confirmed to be JJ012,
      FS090, and 105KC in increasing order on the basis of aggrecan and collagen gene
      expression. The matrix metalloproteinases-1/tissue inhibitors of
      metalloproteinases-1 ratio correlated with the level of differentiation in an
      inverse fashion. Collagenase activity paralleled matrix metalloproteinases
      1/tissue inhibitors of metalloproteinases-1 gene expression and was associated
      with a more invasive phenotype in an in vitro assay. In this report, matrix
      metalloproteinase-1 and tissue inhibitors of metalloproteinases-1 expression in
      human chondrosarcoma tumor cell lines were quantitated, and it was shown that
      interstitial collagenase gene expression correlates inversely with chondrocytic
      differentiation. Differences in collagenase activity and in vitro invasion
      correlate inversely with the level of differentiation. These findings are
      consistent with the hypothesis that collagenase activity is associated with a
      poorer prognosis in chondrosarcoma by facilitating cell egress from the tumor
      matrix.

PMID- 10906889
TI  - Built-in antibiotics to help prosthesis patients.

PMID- 10906890
TI  - Support for support hose.

PMID- 10906891
TI  - Probing Premarin.

PMID- 10906892
TI  - Caring for patients with Alzheimer's disease in Italy.

PMID- 10906893
TI  - Effectiveness of in vitro fertilization with intracytoplasmic sperm injection for
      severe male infertility.
AB  - BACKGROUND: In its 1993 report the Canadian Royal Commission on New Reproductive
      Technologies challenged the effectiveness of in vitro fertilization for severe
      male infertility. To address the Commission's concern, the authors compared the
      relative effectiveness of in vitro fertilization combined with intracytoplasmic
      sperm injection for severe male infertility and conventional in vitro
      fertilization for complete tubal occlusion in women. METHODS: This historical
      cohort study was done at the PROCREA Fertility Centre, a private tertiary human
      reproduction centre in Montreal. Three groups of infertile couples were compared:
      122 couples with severe male infertility treated by in vitro fertilization with
      intracytoplasmic injection of fresh sperm from ejaculate (group 1); 27 couples
      with obstructive azoospermia treated by in vitro fertilization with
      intracytoplasmic injection of epididymal sperm (collected by microepididymal or
      percutaneous epididymal sperm aspiration) (group 2); and 98 couples with tubal
      factor infertility (bilateral tubal occlusion) treated with conventional in vitro
      fertilization (with sperm from ejaculate) (group 3). The main outcomes measured
      were rates of fertilization, pregnancy, clinical pregnancy and implantation.
      RESULTS: Pregnancy rates per started cycle were 35%, 40% and 34% for groups 1, 2
      and 3 respectively. When prognostic factors were controlled for, none of the
      outcome measures differed significantly between the 3 groups. INTERPRETATION: In
      vitro fertilization with intracytoplasmic injection of sperm from the ejaculate
      or the epididymis is as effective for treating severe male infertility as
      conventional in vitro fertilization is for treating complete occlusion of the
      fallopian tubes in women.

PMID- 10906894
TI  - Use of beta-blocker therapy in older patients after acute myocardial infarction
      in Ontario.
AB  - BACKGROUND: Despite its proven efficacy, beta-blocker therapy remains underused
      in elderly patients after myocardial infarction (MI). The objectives of this
      study were to identify undertreated groups of seniors and to determine whether
      older and frailer patients are being selectively dispensed low-dose beta-blocker
      therapy. METHODS: From a comprehensive hospital discharge database, all people
      aged 66 years or more in Ontario who survived an acute MI between April 1993 and
      March 1995 were identified and classified into those who did not receive beta
      blocker therapy and those dispensed low, standard or high doses of this agent.
      Logistic regression models were used to study the effect of age, sex,
      comorbidity, potential contraindications to beta-blocker therapy and residence in
      a long-term-care facility on the odds of not being dispensed a beta-blocker.
      Among beta-blocker users, the odds of being dispensed low relative to standard or
      high doses of this agent were evaluated. RESULTS: Of the 15,542 patients, 7549
      (48.6%) were not dispensed a beta-blocker. Patients 85 years of age or more were
      at greater risk of not receiving beta-blocker therapy (adjusted odds ratio [OR]
      2.8, 95% confidence interval [CI] 2.5-3.2) than were those 66 to 74 years. Having
      a Charlson comorbidity index of 3 or greater was associated with an increased
      risk of not receiving beta-blocker therapy (adjusted OR 1.5, 95% CI 1.3-1.8)
      compared with having lower comorbidity scores. Patients who resided in a long
      term-care facility were at increased risk of not being prescribed beta-blocker
      therapy (adjusted OR 2.6, 95% CI 2.0-3.4). Among the 5453 patients with no
      identifiable contraindication to beta-blocker therapy, women were significantly
      less likely than men to receive this agent (p = 0.005). Of the 6074 patients who
      received beta-blockers, 2248 (37.0%) were dispensed low-dose therapy. Patients
      aged 85 years or more had an increased risk of being dispensed low-dose therapy
      (adjusted OR 1.6, 95% CI 1.3-2.0) compared with those aged 66 to 74 years.
      Compared with those who had the lowest comorbidity scores, patients with the
      highest comorbidity scores were more likely to be dispensed low-dose beta-blocker
      therapy (adjusted OR 1.3, 95% CI 1.0-1.8). INTERPRETATION: Almost half of Ontario
      patients aged 66 or more who survived an MI, particularly those who were older or
      frailer, did not receive beta-blocker therapy. Among those dispensed beta-blocker
      therapy, older and frailer patients were more frequently dispensed low-dose
      therapy.

PMID- 10906895
TI  - Recent versus historical trends in preterm birth in Canada.

PMID- 10906897
TI  - Time to put the Canadian Institutes of Health Research on trial.

PMID- 10906896
TI  - New reproductive technologies: why are we limiting choices for infertile couples?

PMID- 10906898
TI  - Powassan encephalitis.

PMID- 10906899
TI  - Powassan encephalitis: a case report with neuropathology and literature review.

PMID- 10906900
TI  - Unsticking platelets: the role of glycoprotein IIb/IIIa receptor blockade.

PMID- 10906902
TI  - MCC readies a new, computerized medical qualifying exam.

PMID- 10906901
TI  - Recording that elusive rhythm.

PMID- 10906903
TI  - Dr. Krop gets knuckles rapped, but vows to fight college's "inquisition".

PMID- 10906904
TI  - Staffing crisis looms, radiologists warn.

PMID- 10906905
TI  - Ball rolling on research into heading injuries.

PMID- 10906906
TI  - MDs sceptical as BC gives stamp of approval to traditional Chinese medicine.

PMID- 10906909
TI  - The war amputees of Sierra Leone.

PMID- 10906908
TI  - [Summary of the recommendations of the Canadian Consensus Conference on Asthma
      1999. Canadian Asthma Consensus Group].

PMID- 10906910
TI  - Alberta Physician Achievement Review.

PMID- 10906911
TI  - Drug approval times.

PMID- 10906912
TI  - Implementing public-access programs for automated external defibrillation.

PMID- 10906913
TI  - How valid are utilization review tools in assessing appropriate use of acute care
      beds?
AB  - BACKGROUND: Despite their widespread acceptance, utilization review tools, which
      were designed to assess the appropriateness of care in acute care hospitals, have
      not been well validated in Canada. The aim of this study was to assess the
      validity of 3 such tools--ISD (Intensity of service, Severity of illness,
      Discharge screens), AEP (Appropriateness Evaluation Protocol) and MCAP (Managed
      Care Appropriateness Protocol)--as determined by their agreement with the
      clinical judgement of a panel of experts. METHODS: The cases of 75 patients
      admitted to an acute cardiology service were reviewed retrospectively. The
      criteria of each utilization review tool were applied by trained reviewers to
      each day the patients spent in hospital. An abstract of each case prepared in a
      day-by-day format was evaluated independently by 3 cardiologists, using clinical
      judgement to decide the appropriateness of each day spent in hospital. RESULTS:
      The panel considered 92% of the admissions and 67% of the subsequent hospital
      days to be appropriate. The ISD underestimated the appropriateness rates of
      admission and subsequent days; the AEP and MCAP overestimated the appropriateness
      rate of subsequent days in hospital. The kappa statistic of overall agreement
      between tool and panel was 0.45 for ISD, 0.24 for MCAP and 0.25 for AEP,
      indicating poor to fair validity of the tools. INTERPRETATION: Published
      validation studies had average kappa values of 0.32-0.44 (i.e., poor to fair) for
      admission days and for subsequent days in hospital for the 3 tools. The tools
      have only a low level of validity when compared with a panel of experts, which
      raises serious doubts about their usefulness for utilization review.

PMID- 10906914
TI  - Effectiveness of massage therapy for subacute low-back pain: a randomized
      controlled trial.
AB  - BACKGROUND: The effectiveness of massage therapy for low-back pain has not been
      documented. This randomized controlled trial compared comprehensive massage
      therapy (soft-tissue manipulation, remedial exercise and posture education), 2
      components of massage therapy and placebo in the treatment of subacute (between 1
      week and 8 months) low-back pain. METHODS: Subjects with subacute low-back pain
      were randomly assigned to 1 of 4 groups: comprehensive massage therapy (n = 25),
      soft-tissue manipulation only (n = 25), remedial exercise with posture education
      only (n = 22) or a placebo of sham laser therapy (n = 26). Each subject received
      6 treatments within approximately 1 month. Outcome measures obtained at baseline,
      after treatment and at 1-month follow-up consisted of the Roland Disability
      Questionnaire (RDQ), the McGill Pain Questionnaire (PPI and PRI), the State
      Anxiety Index and the Modified Schober test (lumbar range of motion). RESULTS: Of
      the 107 subjects who passed screening, 98 (92%) completed post-treatment tests
      and 91 (85%) completed follow-up tests. Statistically significant differences
      were noted after treatment and at follow-up. The comprehensive massage therapy
      group had improved function (mean RDQ score 1.54 v. 2.86-6.5, p < 0.001), less
      intense pain (mean PPI score 0.42 v. 1.18-1.75, p < 0.001) and a decrease in the
      quality of pain (mean PRI score 2.29 v. 4.55-7.71, p = 0.006) compared with the
      other 3 groups. Clinical significance was evident for the comprehensive massage
      therapy group and the soft-tissue manipulation group on the measure of function.
      At 1-month follow-up 63% of subjects in the comprehensive massage therapy group
      reported no pain as compared with 27% of the soft-tissue manipulation group, 14%
      of the remedial exercise group and 0% of the sham laser therapy group.
      INTERPRETATION: Patients with subacute low-back pain were shown to benefit from
      massage therapy, as regulated by the College of Massage Therapists of Ontario and
      delivered by experienced massage therapists.

PMID- 10906915
TI  - Bias inherent in retrospective waiting-time studies: experience from a vascular
      surgery waiting list.

PMID- 10906916
TI  - Healthy Canadians in 2010?

PMID- 10906917
TI  - Utilization review: can it be improved?

PMID- 10906918
TI  - The new alchemy: transmuting information into knowledge in an electronic age.

PMID- 10906919
TI  - Some light from the heat: implications of rave parties for clinicians.

PMID- 10906920
TI  - Rheumatology: 5. Diagnosis and management of inflammatory polyarthritis.

PMID- 10906921
TI  - A matter of perspective.

PMID- 10906922
TI  - Raves: a review of the culture, the drugs and the prevention of harm.
AB  - Raves are all-night dance parties attended by large numbers of youth, sometimes
      in excess of 20,000. The rave scene, which is international in scope, is
      distinguished by clandestine venues, hypnotic electronic music and the liberal
      use of drugs such as ecstasy (3,4-methylenedioxymethamphetamine), GHB (gamma
      hydroxybutyrate) and ketamine. Several rave-related deaths in Canada in 1999
      alerted health authorities, parents and police to the health risks of rave
      attendance. Family physicians, emergency physicians and pediatricians should have
      some understanding of raves, the drugs and the health risks so they can
      effectively counsel and treat patients. The rave culture in Canada and the drugs
      commonly used at raves are reviewed, and strategies and initiatives for harm
      reduction are discussed.

PMID- 10906907
TI  - Canadian Asthma Consensus Report, 1999. Canadian Asthma Consensus Group.
AB  - OBJECTIVES: To provide physicians with current guidelines for the diagnosis and
      optimal management of asthma in children and adults, including pregnant women and
      the elderly, in office, emergency department, hospital and clinic settings.
      OPTIONS: The consensus group considered the roles of education, avoidance of
      provocative environmental and other factors, diverse pharmacotherapies, delivery
      devices and emergency and in-hospital management of asthma. OUTCOMES: Provision
      of the best control of asthma by confirmation of the diagnosis using objective
      measures, rapid achievement and maintenance of control and regular follow-up.
      EVIDENCE: The key diagnostic and therapeutic recommendations are based on the
      1995 Canadian guidelines and a critical review of the literature by small groups
      before a full meeting of the consensus group. Recommendations are graded
      according to 5 levels of evidence. Differences of opinion were resolved by
      consensus following discussion. VALUES: Respirologists, immunoallergists,
      pediatricians and emergency and family physicians gave prime consideration to the
      achievement and maintenance of optimal control of asthma through avoidance of
      environmental inciters, education of patients and the lowest effective regime of
      pharmacotherapy to reduce morbidity and mortality. BENEFITS, HARMS AND COSTS:
      Adherence to the guidelines should be accompanied by significant reduction in
      patients' symptoms, reduced morbidity and mortality, fewer emergency and hospital
      admissions, fewer adverse side-effects from medications, better quality of life
      for patients and reduced costs. RECOMMENDATIONS: Recommendations are included in
      each section of the report. In summary, after a diagnosis of asthma is made based
      on clinical evaluation, including demonstration of variable airflow obstruction,
      and contributing factors are identified, a treatment plan is established to
      obtain and maintain optimal asthma control. The main components of treatment are
      patient education, environmental control, pharmacotherapy tailored to the
      individual and regular follow-up. VALIDATION: The recommendations were
      distributed to the members of the Canadian Thoracic Society Asthma and Standards
      Committees, as well as members of the board of the Canadian Thoracic Society. In
      addition, collaborating groups representing the Canadian Association of Emergency
      Physicians, the Canadian College of Family Physicians, the Canadian Paediatric
      Society and the Canadian Society of Allergy and Immunology were asked to validate
      the recommendations. The recommendations were discussed at regional meetings
      throughout Canada. They were also compared with the recommendations of other
      similar groups in other countries. DISSEMINATION AND IMPLEMENTATION: An
      implementation committee has established a strategy for disseminating these
      guidelines to physicians, other health professionals and patients and for
      developing tools and means that will help integrate the recommendations into
      current asthma care. The plan is outlined in this report.

PMID- 10906924
TI  - NWT report urges recognition for aboriginal healers.

PMID- 10906923
TI  - Stuttering: an update for physicians.
AB  - Stuttering is a disturbance in the normal fluency and time patterning of speech.
      Developmental stuttering (DS), with or without associated psychiatric illness, is
      the most common form and includes all cases with gradual onset in childhood that
      are not the result of acquired brain damage. Persistent developmental stuttering
      (PDS) is DS that has not undergone spontaneous or speech-therapy-induced
      remission. Organic models of DS focus on incomplete lateralization or abnormal
      cerebral dominance. There is also evidence that DS has a significant genetic
      component to its cause. Neuroimaging research data and the effectiveness of
      dopamine receptor antagonists in DS seem to support the theory of a
      hyperdopaminergic origin. Speech therapy remains the main treatment for DS;
      however, antidepressants can be useful in selected cases. Risperidone, a
      serotonin-dopamine antagonist, has been shown to be more effective than placebo
      in decreasing the severity of stuttering. The long-term efficacy and safety of
      serotonin-dopamine antagonists in DS deserve further study.

PMID- 10906925
TI  - Beware of all types of bat exposure, BC MDs warned.

PMID- 10906926
TI  - Raving on the Internet.

PMID- 10906927
TI  - Raves worry Edmonton MDs, police.

PMID- 10906928
TI  - Drowning in Canada.

PMID- 10906929
TI  - Alberta launches country's first peer-support network for MDs in legal trouble.

PMID- 10906930
TI  - Cheap prescription drugs creating new brand of US tourist in Canada, Mexico.

PMID- 10906931
TI  - Principles for medical care of older persons.

PMID- 10906932
TI  - Drugs for sexually transmitted infections.

PMID- 10906933
TI  - [Prescription of beta-lactams for community-acquired broncho-pulmonary infections
      in adults. Observations in the hospital environment].
AB  - OBJECTIVE: Analyze beta-lactam prescription patterns used in hospitals for the
      treatment of community-acquired lower respiratory tract infections in adults.
      PATIENTS AND METHODS: A prospective study was carried out over 4 months (October
      1997 to January 1998) in 54 medical units caring for lung disease, internal
      medicine/infectious disease, geriatric and general medicine patients in 27
      hospitals representative of the public facilities in France. Data were collected
      on the medical unit, the patients, and the antibiotic prescriptions, including
      discharge prescriptions. The cost analysis of antibiotic therapy took into
      account all antibiotics given to the patients during their hospital stay.
      RESULTS: One thousand eighteen patients were included in the study: 266 were
      treated for acute bronchitis, 405 for bronchitis infection with underlying
      chronic respiratory disease, and 347 for pneumonia. Noteworthy findings included:
      low percentage of protocols within the medical units (25.3%), an unexpected
      frequency of hospitalization for acute bronchitis generally among elderly women,
      and prolonged intravenous antibiotic therapy and hospitalization (5 to 6 days and
      9 to 12.5 days respectively). CONCLUSION: This study confirms the need to
      reinforce measures aimed at optimizing antibiotic prescriptions in hospitals.

PMID- 10906934
TI  - [Muscle hydatidosis. 15 cases].
AB  - OBJECTIVES: The aim of this study was to analyse the epidemiological, diagnostic
      and therapeutic aspects of muscle hydatidosis. PATIENTS AND METHODS: This
      retrospective study included a series of 15 patients with hydatic muscular cysts
      operated on in our service over an eight year period. Five cysts were superficial
      and ten were deep. Patients were predominantly young adults (10 cases); M/F sex
      ratio was 2/1. Clinical signs included atypical pain, particularly for the deep
      localizations, and tumoral formations, particularly for superficial
      localizations. Diagnosis of muscle hydatidosis was made in some patients seen for
      complications or systematic search for another localization. A second hepatic
      localization was found in 5 cases and a splenic localization in one. Sonography
      provided the diagnosis in all cases although the exact localization could not be
      determined. A CT scan was performed in half the cases. Localizations included the
      diaphragm 7 cases, psoas 3 cases, and buttock, triceps, sartorius, anterior
      tibial and intercostal muscles 1 case each. RESULTS: Surgical treatment was the
      same for all abdominal localizations, although different access routes were used.
      Partial pericystostomy was the basic procedure and gave excellent results. One
      case was complicated by a crural nerve lesion that recovered spontaneously.
      Recurrence in the diaphragm occurred in two cases and was successfully treated
      surgically two years later. One patient died due to acute liver failure
      subsequent to multiple cysts which had destroyed the entire liver.

PMID- 10906935
TI  - [Marchiafava-Bignani disease of good prognosis. Two cases].
AB  - BACKGROUND: Marchiafava-Bignami disease or corpus callosum necrosis, is an
      uncommon complication of chronic alcoholism. Prognosis is severe. CASE REPORTS:
      Two young adults with chronic alcoholism who developed Marchiafava-Bignami
      disease initially improved clinically. DISCUSSION: Diagnosis has been facilitated
      with MRI. An MRI exploration should be performed in chronic alcoholic patients
      presenting chronic encephalopathy with dementia, dysarthria, hypertonia, and
      ataxia, or acute encephalopathy with confusion, dumbness, seizures, and
      hypertonia. Necrosis of the corpus callosum gives the diagnosis of Marchiafava
      Bignami disease.

PMID- 10906936
TI  - [Dengue or acute retroviral syndrome?].
AB  - BACKGROUND: The diagnosis of primary HIV infection is a crucial element in the
      fight against the AIDS epidemic. Clinical manifestations associated with primary
      infection are nonspecific. Dengue is a possible differential diagnosis. CASE
      REPORT: A 15-year-old adolescent living in Martinique consulted for a syndrome
      suggestive of infectious mononucleosis. The annual dengue epidemic was at its
      acme at this time. Serum was positive for IgM and the diagnosis of dengue was
      retained. The diagnosis of recent HIV infection was made two months later
      (unprotected homosexual intercourse two weeks before onset of clinical signs).
      Retrospective analysis of the earlier samples at the time of the viral syndrome
      demonstrated that the patient actually had an acute retroviral syndrome.
      DISCUSSION: The clinical and biological manifestations of dengue and primary HIV
      infection are nonspecific and similar to those of infectious mononucleosis.
      Potential exposure to HIV and recent presence in endemic dengue regions (tropical
      areas in America, Asia and Africa) can provide helpful guidance for differential
      diagnosis.

PMID- 10906937
TI  - [Autochthonous cardiac hydatid cyst of favorable outcome].

PMID- 10906938
TI  - [Acute respiratory distress revealing Mediterranean spotted fever].

PMID- 10906939
TI  - [Borreliosis-malaria co-infection: "one course can hide another!"].

PMID- 10906940
TI  - [Arterial antihypertensives in the elderly: the dispute about the old and new!].

PMID- 10906941
TI  - [Controversies over the surgical placebo: legal issues and the ethical debate].
AB  - The debate on controlled surgery trials has had some rather "sensational"
      repercussions, enlivening the placebo issue. In France, there is a consensus on
      the ethical conditions necessary for proper protection of individual persons.
      This consensus has taken on a legal form with the promulgation of the Huriet law.
      For this reason, all studies and research protocols in medicine and surgery are
      examined by ethics committees (CCPPRB) who assess the inclusion conditions within
      the framework of biomedical research and in compliance with the concept that
      individual participants must be give proper protection. These committees are
      faced with increasingly complex situations, particularly concerning the
      pertinence of information give to the participant and the modalities of consent.
      In France, standard measures were established after a parliamentary debate
      issuing from a wider public debate. The issue has become a social transaction
      between biomedical research professionals and the society in general. The
      international debate over the surgery placebo is an interesting illustration of
      how mediation institutions, working along the principles of ethical committees,
      play a key role in social awareness of the ethical issues involved before an
      innovating practice is initiated. But how legitimate are sensational pieces
      published in the media, which as is clearly demonstrated with the debate over the
      surgical placebo, are almost always individual points of view? Shouldn't the
      debate take into account the contributions of ethical committees which integrate
      representatives of the social community as well as the importance of a legal
      framework for individual protection as proposed by the French law? Shouldn't
      personal points of view be counterbalanced by regularly expressed ethical
      committee opinions formed after appropriate ethics-oriented discussion going
      beyond the simple question of "should we do it", a question often dismissed by
      extreme theoretical arguments that leave unanswered the practical question of
      "how should we do it"?

PMID- 10906942
TI  - [A new antibiotic: levofloxacine].

PMID- 10906943
TI  - [Role of spleen cells in protection against malaria].
AB  - IMMUNITY: The anti-infectious effect of the spleen in general and its anti
      malarial effect has been known for a long time. This effect is associated, among
      other functions, with the spleen's capacity to filter and destroy erythrocytes
      parasitized by plasmodies or altered by various physical (heat...) or chemical
      factors. In addition, splenic immunity, which associates specific and nonspecific
      humoral and cellular effector mechanisms is no longer a question of debate. OPEN
      QUESTIONS: There remains nevertheless one aspect of the question to be
      elucidated: the probable interaction between this immunity and other (genetic...)
      factors of the malarious host. CELL FUNCTIONS: This article summarizes current
      knowledge in connection with: a) participation of various cell populations in the
      mechanisms of splenic filtration and phagocytosis and b) genesis of a repertory
      of B and T lymphocytes, plasmodio-specific memory cells. During an infection,
      lymphocytes, monocytes and macrophages are recruited from peripheral blood and,
      in cooperation with cells known as "barrier" cells, increase the capacity of
      splenic filtration/purge and phagocytosis. In addition, the appearance of B and T
      lymphocytes with specific memory of P. falciparum result from hypermutation in VH
      genes (for B lymphocytes) or from clonal selection (for T lymphocytes). The
      folicular dendritic cells accomplish a reserve function. By constantly releasing
      the antigen, these cells would contribute to maintaining immune memory or to
      stimulating naive cells. Further studies are necessary to better understand the
      role of the splenic microcirculation and to identify parasite components which
      stimulate the protective response of the spleen against plasmodies.

PMID- 10906944
TI  - [Vulvodynia].
AB  - DEFINITION: Vulvodynia includes a group of vulva disorders in patients with a
      normal clinical presentation. Chronic and spontaneous complaints are observed,
      sometimes aggravated by sexual intercourse. Most patients complain of a burning
      vulva. MANAGEMENT: The diagnostic and therapeutic approach to vulvodynia is long
      and difficult. Complementary explorations may be useful initially but should not
      be repeated too often. They are helpful in ruling out vulvovaginal infections
      (candidiasis, sexually transmitted diseases) and vulva dermatosis. Vulvodynia can
      then be classed as cyclic vulvo-dynia, vestibulitis or essential (dysesthesic
      vulvodynia). MULTIDISCIPLINARY CARE: Each different type of vulvodynia requires
      specific care. In all cases, the psychosomatic aspect must be considered.
      Multidisciplinary care may involve the primary care physician, the gynecologist,
      the dermatologist, the pain specialist, the psychologist, the psychiatrist, and
      the physical therapy specialist.

PMID- 10906945
TI  - [Multiconceptual therapy in Alzheimer's disease].
AB  - SOCIAL AND ECONOMICAL IMPACT: Alzheimer's disease is a neurodegenerative dementia
      raising major public health concern in industrialized countries. The consequences
      are not only medical but also social and economical. PERSPECTIVES: It is thus
      important to establish diagnostic principles, therapeutic goals, and global
      strategies guiding the behavior of physicians, family and patients faced with
      this dreaded disease. Currently, only a few rare symptomatic treatments are
      available, but research in this field points to potentially effective preventive
      and etiopathogentic therapeutic protocols associating drugs, social support, and
      psychotherapy.

PMID- 10906946
TI  - [Paradoxical embolism with a thrombus in permeable foramen ovale].

PMID- 10906947
TI  - 21st Congress of the European Society of Parenteral and Enteral Nutrition.
      Stockholm, Sweden, September 5-8, 1999. Abstracts.

PMID- 10906948
TI  - Native, industrial and fossil chitins.
AB  - Countless living organisms continuously synthesize and degrade chitin
      enzymatically, for nutritional, morphogenetic and defensive or aggressive
      purposes. Chemically modified chitins are important in the light of their
      biochemical significance in medicine and crop protection; their environmentally
      friendly behaviour permits industrial exploitation of the huge chitinous
      biomasses generated by fishing activities and biotechnology. Chitin is promptly
      metabolized in sediments, and fossil chitin is not frequently encountered.

PMID- 10906949
TI  - Biochemistry of chitin synthase.
AB  - This article compiles the papers dealing with the biochemistry of chitin synthase
      (CS) published during the last decade, provides up-to-date information on the
      state of knowledge and understanding of chitin synthesis in vitro, and points out
      some firmly entrenched ideas and tenets of CS biochemistry that have become of
      age without hardly ever having been critically re-evaluated. The subject is dealt
      with under the headings "Components of the CS reaction" (educt, cation
      requirement and intermediates; product), "Regulation of CS" (cooperativity and
      allostery; non-allosteric activation or priming of CS; latency), "Concerted
      action of CS and enzymes of chitinolysis", "Inhibition of CS", "Multiplicity of
      CSs", and "Structure of CS" (the putative UDPGlcNAc-binding domain of CS;
      identification of CS polypeptides; glycoconjugation). The prospects are outlined
      of obtaining a refined three-dimensional (3D) model of the catalytic site of CS
      for biotechnological applications.

PMID- 10906950
TI  - Chitin biosynthesis and structural organization in vivo.
AB  - Many organisms utilize chitin as a structural component of the protective cell
      walls or exoskeletons which surround them. These structures are light and
      resistant composites with specific structural and mechanical properties which
      allow them to fulfill their protective role. Chitin, in the form of microfibrils,
      is immersed in a matrix of proteins and other polysaccharides. Chitin
      microfibrils provide the high strength which allows them to resist tensions and
      modulus. The cementing compounds protect chitin from chemical attack; keep the
      microfibrils separate, preventing fracture; and provide support to tensions. The
      resulting structures adopt specific forms which are conserved during growth and
      are transmitted in a hereditary fashion. Synthesis of these complex structures
      involves the following steps: (i) synthesis of chitin either intracellularly or
      at the interphase with the extracellular medium; (ii) transport of the chitin
      molecules to the extracellular space; (iii) chemical modification of part of the
      noncrystallized chitin and association with other molecules; (iv) crystallization
      of the unmodified chitin which is covered by the rest of the components. The
      resulting supramolecular structure acquires viscoelastic mechanical properties;
      (v) maturation of the composite through formation of secondary covalent bonds
      among its components, and deposition of different substances.

PMID- 10906951
TI  - Chitin synthases in yeast and fungi.
AB  - The polysaccharide chitin is an important structural component of the cell walls
      of many fungi. Chitin synthesis is directly governed by an enzymatic activity
      called chitin synthase (CS). The use of the budding yeast Saccharomyces
      cerevisiae as a biological model allowed the identification of three distinct
      chitin synthase activities: CSI, involved in repair functions at the end of
      cytokinesis; CSII, responsible for the synthesis of the primary septum that
      separates mother and daughter cells; and CSIII, responsible for the formation of
      the ring (bud scar) where most of the cell wall chitin is located. These chitin
      synthases differ not only in functions but also in catalytic properties. The
      catalytic subunit of each of these activities is encoded by separated genes,
      CHS1, CHS2 and CHS3, respectively, although it has been shown in S. cerevisiae
      that CSIII activity also depends on the products of other genes. To date, several
      chitin synthase (CHS) genes have been also identified in other fungi; most of
      them are similar to ScCHS1 and ScCHS2 genes and are classified in chitin
      synthases classes I, II and III in terms of sequence similarity. The rest are
      defined as two CHS classes, IV and V, highly similar to ScCHS3. While CHS class V
      genes have been only identified in filamentous fungi and their functions are
      unknown, class IV genes, which includes ScCHS3, are involved in the synthesis of
      most chitin in yeast cells.

PMID- 10906952
TI  - Function of chitin oligosaccharides in plant and animal development.
AB  - In plant development chitin oligosaccharides have been studied intensively as
      part of the communication between leguminous plants and Rhizobium bacteria. The
      Rhizobium bacteria synthesize and secrete lipochitin oligosaccharides (LCOs) to
      induce the development of a root nodule, in which the bacteria will infiltrate to
      start a symbiotic relation with the plant. Here we will give an overview of the
      biosynthetic route used by the bacteria to synthesize these LCOs. Perception by
      the plant will also be discussed as well as early responses to the LCOs. By
      working with the genes from the biosynthetic route, other genes were identified
      that share homology with the chitin synthase genes from Rhizobium. These genes
      are now isolated from human, mouse, chick, Xenopus and zebrafish and can be
      divided into three classes. They are mainly expressed during early development at
      the same stage as chitin oligosaccharide synthase activity can be detected. A
      controversy has been risen about their biochemical activity and will be further
      discussed here.

PMID- 10906953
TI  - Molecular and biochemical aspects of chitin synthesis inhibition.
AB  - Chitin, is a beta-1,4-linked aminopolysacharide homopolymer of GlcNAc that occurs
      as a glycoprotein in the exoskeleton of arthropods, the cell wall of fungi and in
      various components of diverse invertebrates. It is synthesized in two different
      ways: in fungi the chitin synthase enzyme occurs as an inactive zymogen in
      vesicles called chitosomes and requires proteolytic activation; in arthropods
      this enzyme is membrane-bound and catalyzes the addition of GlcNAc units to a
      dolichol carrier. Chitin is degraded by three different chitinases, the
      endochitinase that degrades chitin into oligosaccharides of differing chain
      lengths, the exochitinase that degrades oligosaccharides into diacetylchitobiose
      and chitobiase, which degrades diacetylchitobiose into GlcNAc monomers.
      Inhibition of chitin synthesis as well as degradation can both result in
      deleterious effects that are often similar. Chitin synthesis can be blocked
      during the various steps by a variety of antibiotics, metabolic inhibitors,
      insect growth regulators, alkaloids and hormone analogs. During the molting
      process in arthropods, genes are sequentially expressed and repressed by
      developmental hormones. When these hormones or their analogs are administered
      temporally out of sequence, it can result in the blocking of cuticle formation,
      including chitin synthesis. With the advent of biotechnology and the availability
      of both complementary DNA and antibody probes, it is possible to develop high
      throughput assays for discovering new chemicals that can block chitin formation.
      Chitin synthesis inhibitors as well as inhibitors of chitin degradation that
      produce similar effects are promising agents for controlling insect pests, fungal
      pathogens and helminthic parasites.

PMID- 10906954
TI  - Characteristics of chitin-binding proteins from Streptomycetes.
AB  - During growth in the presence of chitin-containing substrates, many Streptomyces
      strains have been shown to secrete formerly unknown, small chitin-binding
      proteins (CHBs) which lack enzymatic activity, specifically target and invade,
      like a glue, alpha-chitin, but not beta-chitin or other polysaccharides. CHBs
      were purified, and their N-terminal amino acids were determined. Deduced
      oligonucleotides were used to identify the corresponding genes, which were then
      sequenced. The deduced CHB1 and CHB2 proteins contain 201 and 200 amino acids,
      respectively, 77.7% of which are identical. Several motifs, including the
      relative location and spacing of four tryptophan residues, are conserved in CHB1
      and CHB2. The affinity of CHB1 to crab shell chitin is two times higher than that
      of CHB2. Comparative studies of various generated mutant CHB1 proteins led to the
      conclusion that mainly one of the exposed tryptophan residues directly
      contributed to the interaction with chitin. Using CHB doupled with FITC
      (fluoresceine isothiocyanate), a highly specific and rapid assay was developed to
      visualize the location of crystalline alpha-chitin within native samples by
      fluorescence or confocal laser microscopy. In contrast, the N-terminal domain (12
      kDa) of the S. olivaceoviridis exochitinase can be used to detect alpha- and beta
      chitin. The structural parameters inducing the recognition and possible loosening
      of alpha-chitin or of alpha- and beta-chitin are at present being investigated.

PMID- 10906955
TI  - Biochemistry of chitinases.
AB  - Chitinases are found in many organisms, and their properties seem to be closely
      related to their biological function. In this chapter, the physicochemical
      properties of chitinases such as molecular size are compared among organisms, and
      the optimum and stability conditions for chitinase activity are described.
      Furthermore, considering their classification based on amino acid sequence,
      kinetic behaviors are discussed together with their biological functions. In
      particular, hydrolytic mechanisms such as inversion and retention of the
      substrate are discussed in relation to allosamidin inhibition.

PMID- 10906957
TI  - Classification of chitinases modules.
AB  - Chitinases frequently display a modular structure featuring a catalytic domain
      attached to one or several ancillary noncatalytic domains whose function is often
      chitin binding. Gene cloning and DNA sequencing have allowed the determination of
      a massive number of amino acid sequences of chitinases during the last 10 years.
      This chapter presents a unifying classification system of the various chitinase
      modules that combines specific features of their sequences, three-dimensional
      structures and reaction mechanisms.

PMID- 10906956
TI  - The structure and action of chitinases.
AB  - Chitin is second only to cellulose in biomass and it is an important component of
      many cell wall structures. Several families of enzymes, of distinctly different
      structure, have evolved to hydrolyze this important polysaccaride. Glycohydrolase
      family 18 enzymes, chitinases, are characterized by an eight-fold alpha/beta
      barrel structure; it has representatives among bacteria, fungi, and higher
      plants. In general these chitinases act through a retaining mechanism in which
      beta linked polymer is cleaved to release a beta anomer product. Family 19
      chitinases are found primarily in plants but some are found in bacteria. Members
      of this family are related to one another by amino acid sequence, but are
      unrelated to family 18 proteins. They have a bilobal structure with a high alpha
      helical content. Despite any significant sequence homology with lysozymes,
      structural analysis reveals that family 19 chitinases, together with family 46
      chitosanases, are similar to several lysozymes including those from T4-phage and
      from goose. The structures reveal that the different enzyme groups arose from a
      common ancestor glycohydrolase antecedent to the procaryotic/eucaryotic
      divergence. In general, the family 19 enzymes operate through an inverting
      mechanism.

PMID- 10906958
TI  - Aggressive and defensive roles for chitinases.
AB  - Chitinases are produced by a wide variety of pathogenic and parasitic microbes
      and invertebrates during their attack on chitin-containing organisms. Examples
      discussed include enzymes of insect and algal viruses, of yeast killer toxin
      plasmids, of bacterial and fungal pathogens of fungi and insects, and of
      parasitic protozoa. These chitinases play roles in penetration of fungal cell
      walls, and of exoskeletons and peritrophic membranes of arthropods. Salivas of
      some invertebrate predators have chitinolytic activity which may be involved in
      their attack on their prey. Chitinases play a major defensive role in all plants
      against attack by fungi, and perhaps also against attack by insect pests. The
      plant chitinases form a very large and diverse assemblage of enzymes from two
      families of glycosyl hydrolases. At least some vertebrates, including fish and
      humans, also may utilise chitinases in their defence against pathogenic fungi and
      some parasites.

PMID- 10906959
TI  - Chitinases in biological control.
AB  - The public concern over the harmful effects of chemical pesticides on the
      environment and human health has enhanced the search for safer, environmentally
      friendly control alternatives. Control of plant pests by the application of
      biological agents holds great promise as an alternative to the use of chemicals.
      It is generally recognized that biological control agents are safer and more
      environmentally sound than is reliance on the use of high volumes of pesticides.
      Due to the importance of chitinolytic enzymes in insect, nematode, and fungal
      growth and development, they are receiving attention in regard to their
      development as biopesticides or chemical defense proteins in transgenic plants
      and microbial biocontrol agents. In this sense, biological control of some soil
      borne fungal diseases has been correlated with chitinase production. Fungi- and
      bacteria-producing chitinases exhibit antagonism against fungi, and inhibition of
      fungal growth by plant chitinases has been demonstrated. Insect pathogenic fungi
      have considerable potential for the biological control of insect pests.
      Entomopathogenic fungi apparently overcome physical barriers of the host by
      producing multiple extracellular enzymes including chitinolytic enzymes, which
      help to penetrate the cuticle and facilitate infection. In this chapter, the role
      of chitinases in biological control and their potential use in the improvement of
      biocontrol agents and crop plants by genetic engineering is analyzed in view of
      recent findings.

PMID- 10906960
TI  - Host-parasite interactions: elicitation of defense responses in plants with
      chitosan.
AB  - The plant's defense response against pathogens can be elicited by numerous
      external signals. Plant pathogens known to be incompatible on a given plant
      species can elicit strong disease resistance responses, whereas an adapted
      compatible pathogen generates a weaker response and thus can more readily infect
      the plant tissue. The plant's response can be manipulated genetically by the
      transfer of "R" genes (single dominant genes for race-specific disease
      resistance) or by treatment with elicitors such as chitosan. Both of these
      manipulations can result in the rapid activation of a subset of genes called PR
      (pathogenesis-related) genes, generally regarded as the genes that functionally
      develop disease resistance. There appear to be multiple modes by which chitosan
      can increase PR gene function, including activating cell surface or membrane
      receptors and internal effects on the plant's DNA conformation that in turn
      influence gene transcription. A novel strategy for controlling PR gene expression
      proposes to transform plants with a chitosan-inducible gene promoter linked in
      line with a single signal gene capable of rapid, intense induction of an entire
      set of PR genes, thereby enabling the control of disease resistance by external
      chitosan applications.

PMID- 10906961
TI  - Inhibitors of chitinases.
AB  - In this review we describe inhibition of chitinases from bacteria, fungi, plants
      and animals by allosamidin and its derivatives, cyclic peptides, styloguanidin
      and divalent cations. Most information is available for allosamidin, whose
      important structural features necessary for inhibition are known. At least one N
      acetylallosamine sugar must be present, and the spatial arrangement of the
      allosamizoline moiety are important for inhibition. Less complex compounds are
      therefore possible as lead structures for the development of agents interfering
      with chitinase. There is a pronounced species specificity in chitinase inhibition
      by allosamidin: half-maximal values are often in the range of 0.1-1 microM (e.g.
      in all arthropods), being lower in nematodes (0.048, 0.0002 microM, respectively)
      and amoeba (0.002-0.01 microM) and quite divergent in fungi (0.01-70 microM).
      These differences cannot be caused by the catalytic centers of family 18 and 19
      chitinases.

PMID- 10906962
TI  - Mammalian chitinase-like proteins.
AB  - Mammals express genes coding for proteins that show significant similarity to
      chitinases of family 18 glycosyl hydrolases. These chitinase-like proteins have
      no chitinase activity due to changes in critical residues in the putative active
      center. One of these is oviductin, a high molecular weight glycoprotein most
      likely involved in fertilization and protection of the tubal epithelium owing to
      its mucin character. Another is YKL-40 (HCgp39) produced in association with
      tissue remodeling. Such proteins could have a general function in morphogenesis.

PMID- 10906963
TI  - Chitinases of human parasites and their implications as antiparasitic targets.
AB  - Pathogens causing a number of human and animal diseases use chitin and chitinases
      in their life cycles. Most of these diseases are caused by protozoan or metazoan
      pathogenic parasites. Some of these parasites contain chitin coats that protect
      them from the harsh conditions in the animal body or the environment. Some
      pathogens use chitinase to invade or exploit the chitin-containing structures of
      their host to establish successful infection or to be transmitted from one
      vertebrate to another via insect vectors. Recent studies indicate that each of
      these organisms has evolved to use chitin and chitinases differently and in a
      developmental stage-specific manner. Genes of many of these pathogenic parasites
      have been isolated, and the predicted amino acid sequences show a great deal of
      diversity. In this chapter we will discuss the roles chitin and chitinases play
      in several animal diseases, the strategies used to clone the chitinase genes from
      various parasites and the usefulness of chitinases as preventive or therapeutic
      agents.

PMID- 10906964
TI  - Analytical biochemistry and clinical significance of N-acetyl-beta-D
      glucosaminidase and related enzymes.
AB  - Human N-acetyl-beta-D-glucosaminidase, N-acetyl-alpha-D-glucosaminidase, endo
      beta-N-acetylglucosaminidase, hexosaminidase, beta-N-acetylgalactosaminidase and
      glucocerebrosidase have not been so widely studied as the beta-N
      acetylhexosaminidases in bacteria, fungi and arthropods. Their biochemical role
      has been elucidated, however, and their urinary and plasma determination is being
      adopted for the early detection of diseases before clinical manifestation, in
      particular for hypertension, renal injuries and disorders, depression and
      lysosomal storage diseases. The spectrophotometric determinations of N-acetyl
      beta-D-glucosaminidase, most often done with 3-cresolsulphone phthaleinyl N
      acetyl-beta-D-glucosaminide, have been recently simplified and adapted to
      automatic instruments.

PMID- 10906965
TI  - Biochemistry, histology and clinical uses of chitins and chitosans in wound
      healing.
AB  - Biodegradability, biocompatibility and capacity to promote the synthesis of
      hyaluronan are main characteristics of chitin-derived wound healing materials,
      whose biological significance in the human body depends largely on the actions
      that certain hydrolases exert on them. The resulting chitooligomers stimulate
      various cells, while the released monomers are phosphorylated and incorporated
      into hyaluronan, keratan sulphate and chondroitin sulphate, components of the
      intracellular matrix and connective tissue. The healing process favoured by these
      materials is examined in terms of macrophage activation, cytokine production by
      macrophages and fibroblasts, antiinflammatory action, angiogenesis stimulation,
      granulation and scar formation. Current biomedical applications are illustrated
      by the treatment of leg ulcers, the use of skin substitutes, and the regeneration
      of bone, nerve and meniscus tissues.

PMID- 10906966
TI  - Veterinary practice with chitin and chitosan.
AB  - Dramatic effects of chitin and chitosan on wound healing were demonstrated in
      field cases of many small animals (dogs and cats), food animals (338 cows) and
      142 zoo animals. In comparison with conventional therapy with irrigation and
      antibiotic administration to wound, new treatment with chitin and chitosan
      permitted a substantial decrease in treatment frequency with minimum scar
      formation.

PMID- 10906967
TI  - Immunological aspects of chitin and chitin derivatives administered to animals.
AB  - Chitosan amino groups are recognized by the immune system. Therefore, every
      derivative of chitin should be assayed immunologically if biomedical applications
      are sought. Macrophages are activated to various extents by chitin derivatives.
      Deacetylated chitin (30% deacetylation) and chitin sulfate stimulate the
      production of circulating antibodies. Accumulation of carboxymethyl chitin takes
      place in granulocytes and macrophages. These polysaccharides activate complement
      in analogy to zymosan. Intraperitoneal injection of N-acetylchitohexaose inhibits
      the growth of tumor cells and pathogens on a similar level as that of lentinan.

PMID- 10906968
TI  - Clinical and biochemical evaluation of chitosan for hypercholesterolemia and
      overweight control.
AB  - After providing basic information on enzymes involved in cholesterol homeostasis,
      and on management of hypertriglyceremia and hypercholesterolemia, with the aid of
      cholestyramine and fibric acid, this chapter examines the effects of the
      ingestion of chitosan. Dietary chitosan is effective on serum cholesterol and in
      atherosclerosis in normal and diabetic mice, and lends itself to the treatment of
      hypercholesterolemia in humans. It also exhibits antiulcer, antiarthritic,
      antihypertension and antiuricemic properties. The published human trials,
      analysed statistically, further indicate that chitosan is effective to control
      overweight when associated to a diet. This chapter discusses several issues
      raised against the use of chitosan, namely, depletion of zinc and liposoluble
      vitamins, as well as advantages such as enhanced absorption of nutrients and
      competitive inhibition of lipases. It also directs attention to the unexplored
      areas of fungal and algal chitosans, and the use of chitins instead of chitosans.

PMID- 10906969
TI  - Microparticulate drug delivery systems.
AB  - Chitosan was proposed as a drug carrier for mucosal administration in ocular,
      buccal, nasal, gastroenteric and vaginal-uterine therapies based on its
      bioadhesive properties and biodegradability in vivo under the action of
      hydrolases. Examples are the delivery of acyclovir via ocular administration, and
      the delivery of 5-aminosalicylic acid to the colon. Microparticles may need to be
      cross-linked to retard their degradation in acidic media; yet cross-linking with
      glutaraldehyde introduces cytotoxic characteristics and depresses bioadhesion.
      Alternative cross-linking approaches are discussed along with the suitability of
      chitosan for the oral delivery of vaccines.

PMID- 10906970
TI  - Antimicrobial action of exogenous chitosan.
AB  - The objective of this chapter is to present fundamental factors (e.g. intrinsic
      and extrinsic) influencing chitosan as antimicrobial agent, for effective
      practical application. The antimicrobial activity of chitosan is well observed on
      a wide variety of micro-organisms including fungi, algae and some bacteria.
      However, the antimicrobial action is influenced by intrinsic and extrinsic
      factors such as the type of chitosan (e.g. plain or derivative); degree of
      chitosan polymerization; host natural nutrient constituency; substrate chemical
      and/or nutrient composition; and environmental conditions (e.g. substrate water
      activity (Aw) and/or moisture). Although both plain and derivative chitosans are
      effective as antimicrobial agents, there is a differential effect between them.
      Their differential antimicrobial effect is mainly exhibited in live host plants;
      thus the antifungal effect of N-carboxymethyl chitosan (NCMC) is different in
      vegetable as compared with graminea host. At the same time, pentamer and heptamer
      chitosan units seem to have better antifungal action than larger units. Chitosan
      antimicrobial action is more immediate on fungi and algae, followed by bacteria;
      the chitosan site of action is at the microbial cell wall.

PMID- 10906971
TI  - [The eyes and the tropical regions].

PMID- 10906972
TI  - [Ocular health in Africa: a public health problem. The mobilization program of
      the French Ministry of Cooperation].

PMID- 10906973
TI  - [The adversary: blindness].

PMID- 10906974
TI  - [Blindness in Benin].
AB  - A population-based survey of the prevalence and cause of blindness and poor
      vision was conducted in the Republic of Benin in 1990 using a stratified cluster
      random sampling procedure. The survey was designed and implemented through the
      collaboration of the Ministry of Health of the Republic of Benin and the
      Programme for the Prevention of Blindness of the World Health Organization
      (WHO/PBL). Survey data were analyzed at the International Centre for Eye Health,
      Institute of Ophthalmology, University of London, United Kingdom. In accordance
      with the procedures recommended by WHO/PBL, 7272 individuals were recruited and
      7047 were examined. The survey achieved excellent coverage in all locations with
      an overall coverage of 96.9%. The prevalence of blindness (visual acuity less
      than 3/60 in the better eye) was 0.6% (CI95% = 0.4%-0.9%). The prevalence of poor
      vision (best vision less than 6/60 but not blind in the better eye) was estimated
      at 2.6% (CI95% = 2.1%-3.1%). The major causes of blindness were age-related
      cataract and glaucoma (54% and 15% respectively of blind people recruited). The
      major cause of poor vision were cataract, refractive errors, and macular
      disorders (64%, 9.6%, and 9.0% respectively of people recruited with poor vision.
      The survey results indicate that there is an urgent need for basic eye care
      services. Cataract has been designated as a priority target in the recently
      designed National Blindness Prevention Programme now being implemented in the
      Republic of Benin. With proper management of this problem, the current prevalence
      of blindness and poor vision could be reduced by at least 45%. At the end of this
      cluster study, the design effect (D = 1.56) and rate of homogeneity (ROH = 0.002)
      were computed for an average number of 250 people per cluster.

PMID- 10906975
TI  - [Ophthalmologists without borders in Northern Cameroon].
AB  - Ophthalmologist without Borders (OWB) is a non-governmental organization founded
      in 1987 that operates mainly through medical and surgical care centers located in
      northern Cameroon. The goal of OWB is advancement of the fight against blindness
      and low vision in the third world. To achieve this goal OWB has four activities.
      In less than 10 years OWB has dispensed more than 90,000 consultations not only
      to patients with cataracts, the first cause of curable blindness, but also to
      numerous patients with conjunctivitis. Surgical therapy is another major activity
      of the OWB which has performed over 15,000 procedures with cataracts accounting
      for 85% of indications. Results have been encouraging but have demonstrated the
      need for dauntless surgeons and the importance of postoperative follow-up.
      Prevention and screening are priorities that are being progressively implemented.
      Training is an essential part of the mission of OWB with the ultimate aim being
      to leave local physicians and nurses with adequate facilities.

PMID- 10906976
TI  - [Cataract-related blindness in Morocco. The Moroccan Group of Epidemiologic
      Evaluation of Blindness].
AB  - The lack of sound and recent epidemiological data on the prevalence and causes of
      blindness has hampered the development and evaluation of the Moroccan Programme
      for the Prevention of Blindness. For this reason a population-based survey using
      a stratified (urban/rural) sampling design for random selection of clusters was
      carried out in the Kingdom of Morocco from May 15 until June 30, 1992. The
      procedures used for this survey were those proposed by the WHO Programme for the
      Prevention of Blindness. A total of 10,198 people were recruited and 8878
      examined for a participation rate of 87%. The size and representativity of the
      sample satisfactorily guaranteed the order of magnitude and accuracy of eye
      health indicators used by health planners. The crude point prevalence of
      blindness was 0.8%, that of bilateral poor vision was 2.3%, and that of
      unilateral poor vision was estimated to be 2.8%. Based on these findings 195,000
      people would be blind and 1,300,000 would be at risk of becoming so, for a total
      of approximately 1,500,000 people with serious visual impairment. Age-related
      cataract was the most important cause of blindness (45.5%) and bilateral poor
      vision (43.1%). The prevalence of cataract-related visual impairment--operable or
      inoperable--was estimated to be 2.1% of the survey sample. Applying a realistic
      algorithm to the survey data, it was estimated that the backlog for cataract
      surgery in Morocco in 1992 was in the order of 502,000 eyes in approximately
      287,000 people. The percentage of patients who had undergone cataract surgery in
      hospital was 0.8%. Posterior lens dislocation according to the traditional
      "couching" method was noted in 0.1% of people studied. It was estimated that 25%
      of the demand for cataract surgery was covered by available facilities and that
      40% of people with aphakia could not obtain eye care.

PMID- 10906977
TI  - [Mass treatment of onchocerciasis in 1996].
AB  - Mass treatment of onchocerciasis has changed radically in the last 20 years. With
      implementation of the Onchocerciasis Control Programme (OCP), use of insecticides
      to control vector larvae has been effective but has not been extended to all
      infected areas due to the cost. The consequences of this problem have been
      lessened thanks to ivermectin, an effective drug that can be administered in a
      single yearly dose. Although ivermectin does not appear to induce major side
      effects, surveillance is necessary after administration in polyparasitized
      subjects living in zones where loaiasis is present and in hypermicrofilaremic
      subjects. To assist in the fight against onchocerciasis, ivermectin is
      distributed free of charge through the Mectizan Foundation by Merck Laboratories.
      Inexpensive community distribution programs with active participation of the
      populations at risk have demonstrated their usefulness. The results of mass
      treatment through the Mectizan Foundation have been excellent. Non-governmental
      organizations and in particular the Organization for the Prevention of Blindness
      (OPB) have become increasingly involved in the fight against onchocerciasis. The
      campaign conducted by the OPB in Mali, Senegal and Guinea illustrate this
      involvement. The role of non-governmental organizations expanded greatly with the
      implementation of the APOC programme supported by the World Bank.

PMID- 10906978
TI  - [Ocular cysticercosis].
AB  - Ocular cysticercosis results from development of Taenia solium larvae,
      Cysticercus cellulosae, in the eye. This condition is observed all over the world
      but is particularly common in developing countries. The eye, like nervous system
      and muscle tissue, is a prime location for parasitic development because of its
      rich vascularization. Intraorbital cysticercosis accounts for 75 to 85% of cases
      and if untreated leads to blindness. Intravitreal involvement is the most common
      followed by subretinal involvement. Involvement of other structures such as the
      camera aqueosa, iris, and crystalline lens is rare. Diagnosis of intraocular
      cysticercosis is straightforward when cysticerci are visible. Immunologic testing
      of aqueous humor using ELISA, western-blot, or immunodetection of circulating
      antigens can be useful diagnostic techniques in patients with opacification of
      the eye. Involvement of the orbit, palpebra, conjunctiva, and lacrimal glands is
      observed in 20 to 25% of cases. Diagnosis of adnexal involvement is facilitated
      by ultrasonography and CT-scan. Drug therapy for ocular manifestations of
      cysticercosis is ineffective and hastens progression of the disease by
      exacerbating the inflammatory response. Surgical treatment is the only
      alternative. Significant progress has been made thanks to new microsurgical
      vitreal and retinal procedures but these techniques are often unavailable in
      developing countries. The severity of ocular cysticercosis and poor management
      facilities in developing countries underlines the need for prevention by sanitary
      measures and health education.

PMID- 10906980
TI  - [Amebic keratitis].
AB  - Amoebic keratitis is an uncommon pathology mainly implicated in eye infection in
      contact lens wearers. The offending parasite is a free-living amoeba of the genus
      Acanthamoeba. Diagnosis is often delayed because clinical signs are confusing
      especially at the onset. Samples for parasitic tests should be taken not only for
      the infection site but also from the lenses and cleaning products. A standard
      treatment of amoebic keratitis has not been established. Several drugs are
      theoretically active but achieve inconsistent results. Recently keratitis has
      been observed at a seemingly high incidence in developing countries but
      epidemiologic data is still scarce.

PMID- 10906979
TI  - [Xerophthalmia: current data].
AB  - Xerophthalmia is a term covering a range of ophthalmologic manifestations due to
      vitamin A deficiency. This condition occurs in preschool children in tropical
      regions affected by protein-caloric malnutrition. Clinical manifestations of the
      disease have been summarized in the 1974 five-grade WHO classification. Clinical
      diagnosis was traditionally made using a slit lamp to detect the pathognomonic
      manifestations and consequences of corneal and conjunctival xerosis. Currently
      diagnosis is greatly facilitated by determination of plasma levels using a
      micromethod, especially the relative dose response (RDR) test, and by
      conjunctival impression cytology (CIC). CIC is a simple and reliable method which
      allows mass screening and thus more effective evaluation of the impact of
      xerophthalmia on public health in Africa. The relationship between xerophthalmia
      and measles is complex. Vitamin A deficiency promotes measles which can in turn
      hasten perforation of keratomalacia especially in undernourished children.
      Vitamin A has a beneficial effect on both xerophthamia and measles. Curative and
      prophylactic administration of vitamin A at doses recommended by the W.H.O.
      considerably reduces not only xerophthalmia-related morbidity but also child
      mortality in tropical areas.

PMID- 10906981
TI  - [Corneal blindness in tropical areas].
AB  - Corneal disease is the second most common cause of blindness in tropical
      countries after cataract. It mainly strikes children who are exposed to numerous
      infectious agents against which they are unprotected due to the absence of basic
      health care. In high risk groups, the incidence of childhood corneal-related
      blindness is more than 20 times higher than in developed countries. There are
      many causes of corneal-related blindness. Endemic trachoma persists in some areas
      and inflammatory forms can lead to blindness. Eradication requires instillation
      of antibiotics in the eye, improvement of sanitary conditions, and campaigns
      against promiscuity. Xerophthalmia can induce blindness by perforation of the
      cornea in children with vitamin A deficiency. Measles, herpes simplex keratitis,
      and corneal ulcer that progresses to bacterial or fungal infections, or to amebic
      keratitis are also major causes of corneal-related blindness. The incidence of
      onchocerciasis is decreasing thanks to treatment with ivermectin and programs to
      control simulium. Neonatal gonococcal ophthalmia and leprosy-associated ocular
      disease can also lead to blindness. This overview of the various causes
      illustrates the close correlation between the level of life and living conditions
      and the occurrence of corneal-related blindness in tropical areas.

PMID- 10906982
TI  - [Retinal complications in hemoglobinopathies: report of 32 cases].
AB  - Hemoglobinopathies especially sickle cell disease causes neovascularization in
      the retina and lead to hemorrhage. To gain insight into the features and
      incidence of this retinopathy, a study was carried out in Lome, Togo, in 32
      subjects (mean age: 31.1 years) presenting hemoglobinopathy. There were 25
      patients with SC disease, 3 with SS, 2 with AC, and 2 with A2F. All were examined
      by the same ophthalmologist and underwent fluorescein angiography. Retinopathy
      was observed in 22 of the 32 patients including 21 of the 25 patients (84%) with
      SC and one patient with AC who presented macular hemorrhage. The main findings in
      patients with SC were formation of new blood vessels in the peripheral retina
      characteristic of proliferating retinopathy in 11 cases, black sun spots
      characteristic of non-proliferating retinopathy in 3 cases, and evidence of
      vitreous hemorrhage in 2 cases. These findings confirm the high incidence and
      seriousness of retinal complications in patients with SC disease. Prevention is
      necessary and requires systematic screening to allow early detection of
      complications which can be treated by laser photocoagulation.

PMID- 10906983
TI  - [Management of postoperative endophthalmitis epidemics in tropical areas. Report
      of 24 cases seen at the Tropical Ophthalmology Institute of Africa].
AB  - An epidemic of postoperative endophthalmitis occurred at the Tropical
      Ophthalmology Institute of Africa in September 1994. Due to the seriousness of
      this outbreak, a survey was undertaken to diagnose cases, trace the origin of
      contamination within the facilities and staff, and screen for the organism in
      patients with or without endophthalmitis. A total of 24 cases of endophthalmitis
      following 118 procedures involving the eyeball were found. There was no
      significant correlation between the occurrence of endophthalmitis and sex, age,
      type of surgery, surgeon, surgical assistant, operating room staff, postoperative
      complications, operating room, care providers, or type of hospitalisation. There
      was a significant correlation between the occurrence of endophthalmitis and the
      presence of secretions on the first bandage. Staphylococcus aureus was identified
      in 16 cases and in one patient hospitalized for an ulcer of the cornea.
      Staphylococcus aureus contamination was found in two fluids used for eye washing.
      We conclude that the probable cause of this epidemic was nosocomial infection and
      emphasize the importance of maintaining basic sterility measures despite the need
      to minimize costs in developing countries.

PMID- 10906984
TI  - [Conjunctival dirofilariasis caused by Dirofilaria repens: report of a French
      case].
AB  - Dirofilariasis involving Dirofilaria repens is an exceedingly rare event in
      France. Most cases have involved subcutaneous lesions but ocular and peri-ocular
      involvement have been observed. The present report describes a case of
      dirofilariasis involving the conjunctiva in a 61 year-old-man in France. Onset
      was characterized by the sudden appearance of painful conjunctival cyst. Clinical
      examination and laboratory tests did not allow diagnosis. Opening the cyst and
      extracting the parasite allowed diagnosis and treatment. Microscopic examination
      identified the parasite as a female Dirofilaria repens. This new case of ocular
      dirofilariasis emphasizes that this parasitic disease is present and probably
      underestimated in mainland France. Opening of the conjunctival cyst allowed
      identification of the parasite and successful treatment without sequels.

PMID- 10906985
TI  - [Harada's disease. Report of a case].
AB  - Harada's disease is a uveo-meningitis syndrome characterized by meningo
      encephalic manifestations preceded by bilateral posterior uveal lesions. The
      etiology of Harada's disease is still unclear but it probably involves an auto
      immune reaction to melanocytes. This mechanism would account for the high
      incidence of Harada's disease in dark-skinned patients. This report describes a
      case of Harada's disease that occurred in a 28-year-old woman from North Africa.
      Ophthalmologic manifestations were typical with regard to clinical features and
      course involving bilateral papillary edema followed by exsudative detachment of
      the retina and diffuse cicatricial epitheliopathy of the posterior poles. However
      neurologic signs were mild, the main finding being atypical headache, and this
      particularity delayed diagnosis. Limited cerebral involvement that did not
      coincide with ocular lesions explains the fact that a thorough search for
      posterior uveal involvement with the aforesaid features was necessary. Although
      it occurs mainly in dark-skinned Asians, Harada's disease deserves the attention
      of physicians practicing in tropical areas.

PMID- 10906987
TI  - [The Institute of Tropical Ophthalmology of Africa].
AB  - The Tropical Ophthalmology Institute of Africa (TOIA) is an integral part of the
      OCCGE. Located in Bamako since 1953, the TOIA is operated jointly by the member
      states of the OCCGE, the French Cooperation Ministry, and the WHO for which it
      serves as a center for the prevention of blindness. In addition to providing eye
      care for the people of western Africa, the TOIA promotes clinical, epidemiologic,
      and surgical research and carries out health surveys in function of the needs of
      the member states of the OCCGE. The major purpose of the TOIA is to training
      doctors and ophthalmologic nurses as well as for cataract operators and
      eyeglasses technicians. At the center of a network dedicated to the fight against
      blindness, the range of action of the TOIA now reaches beyond the borders of the
      eight states in the OCCGE.

PMID- 10906986
TI  - [Unusual case of bilateral optic neuritis in Lyme neuroborreliosis].
AB  - The most common manifestations of Lyme disease are neurologic and rheumatologic,
      but ophthalmologic lesions can also occur and may even be dominant. The authors
      describe a case of bilateral optic neuropathy associated with Lyme borreliosis
      that quickly led to near-total blindness. In addition to a loss in visual acuity
      and field bilateral papillary edema was documented by angiofluorography. A
      spectacular improvement was obtained under combined antimicrobial therapy using
      doxycycline and corticosteroid therapy. The patient rapidly recovered full
      vision. These observations are discussed within the context of Lyme disease with
      a review of other relevant ophthalmologic complications. The importance of
      careful interpretation of serology is emphasized.

PMID- 10906988
TI  - Enzymology of nitric oxide synthases.

PMID- 10906989
TI  - Purification of the inducible nitric oxide synthase.

PMID- 10906990
TI  - Purification of the constitutive nitric oxide synthase.

PMID- 10906991
TI  - Cloning and expression of human inducible nitric oxide synthase.

PMID- 10906992
TI  - Cloning and expression of human eNOS and nNOS using the baculovirus-insect cell
      system.

PMID- 10906993
TI  - Assay of NOS activity by the measurement of conversion of oxyhemoglobin to
      methemoglobin by NO.

PMID- 10906994
TI  - Measurement of NOS activity by conversion of radiolabeled arginine to citrulline
      using ion-exchange separation.

PMID- 10906995
TI  - Radiochemical measurement of NOS activity by conversion of [14C]L-arginine to
      citrulline using HPLC separation.

PMID- 10906996
TI  - The enzymatic measurement of nitrate and nitrite.

PMID- 10906997
TI  - Determination of NOS activity using cyclic-GMP formation.

PMID- 10906998
TI  - Determination of NO with a Clark-type electrode.

PMID- 10906999
TI  - The measurement of NO in biological systems using chemiluminescence.

PMID- 10907000
TI  - Measurement of NO using electron paramagnetic resonance.

PMID- 10907001
TI  - Measurement of eNOS and iNOS mRNA expression using reverse transcription
      polymerase chain reaction.

PMID- 10907002
TI  - Measurement of NOS mRNA by northern blotting and the ribonuclease-protection
      assay.

PMID- 10907004
TI  - Immunohistochemical localization of NOS isoforms.

PMID- 10907003
TI  - Detection of NOS isoforms by western-blot analysis.

PMID- 10907005
TI  - A practical protocol for the demonstration of NOS using in-situ hybridization.

PMID- 10907006
TI  - Use of NO donors in biological systems.

PMID- 10907007
TI  - Making and working with peroxynitrite.

PMID- 10907008
TI  - The use of NO gas in biological systems.

PMID- 10907009
TI  - A microtiter-plate assay of human NOS isoforms.

PMID- 10907010
TI  - Use of arginine analogs as inhibitors of nitric oxide synthase in rat-aortic
      rings.

PMID- 10907011
TI  - Measurement of biopterin and the use of inhibitors of biopterin biosynthesis.

PMID- 10907012
TI  - A sensitive assay for the enzymatic activity of GTP cyclohydrolase I.

PMID- 10907013
TI  - Simultaneous measurement of mitochondrial function and NO.

PMID- 10907014
TI  - Release of NO from donor compounds: a mathematical model for calculation of NO
      concentrations in the presence of oxygen.

PMID- 10907015
TI  - The determination of nitrotyrosine residues in proteins.

PMID- 10907016
TI  - Measurement of DNA damage using the comet assay.

PMID- 10907017
TI  - Methods for the study of NO-induced apoptosis in cultured cells.

PMID- 10907018
TI  - [Antibiotics in treatment of respiratory tract infection].
AB  - Antibiotics are discussed in sequential therapy of respiratory tract infection.
      Penetration into bronchial tissue and bronchial resistance are presented as a
      main therapeutical problem.

PMID- 10907019
TI  - [White blood cell picture of the peripheral blood of psoriatic patients treated
      with PUVA and cignoline].
AB  - White blood cell picture of the peripheral blood was determined in 37 patients
      with psoriasis vulgaris treated with PUVA and cignoline. The studies were
      performed during active period of the disease, during its treatment and in the
      initial period of the remission. The results were compared with those obtained in
      20 healthy age-matched persons and they were correlated with the skin surface
      area involved, duration of the diseases and duration of its latest relapse. In
      the active period of the disease per cent of peripheral blood neutrophils and
      basophils is significantly increased, while per cent of lymphocytes is lowered.
      Increased per cent of neutrophils positively correlates with the skin surface
      area involvement.

PMID- 10907020
TI  - [In vitro studies on anemia in chronic inflammatory disease: influence of
      interleukin-6 on human erythropoietin].
AB  - The influence of interleukin-6 (Il-6) on human erythropoietic progenitors growth
      in vitro was evaluated. It was found Il-6 causes approximately 35% inhibition of
      early BFU-E growth stimulated with erythropoietin, kit ligand and interleukin-3,
      Il-6 did not inhibit erythroid colony formation by late BFU-E and CFU-E
      progenitors. This data suggests the role Il-6 as one of inflammatory cytokines in
      pathogenesis of anemia of chronic disease acting inhibitory at early BFU-E
      erythroid progenitors level.

PMID- 10907021
TI  - [Triiodothyroxine (T3), thyroxine (T4), thyreotropine (TSH) and myoglobin levels
      in patients with myasthenia gravis].
AB  - T3, T4, TSH and myoglobin levels were determined in 14 patients with myasthenia
      gravis and compared with thirty one healthy control subjects. Significant
      decrease of myoglobin concentration and increase T3, T4 levels as compared to
      control group was found. TSH concentration was in normal range. Duration of
      myasthenia, level of disease (according to Osserman classification) and kind of
      therapy not influenced on detectable variations myoglobin, T3, T4 and TSH
      concentration.

PMID- 10907022
TI  - [Influence of nitrates on red blood cell deformability and clinical parameters in
      patients with silent ischemia].
AB  - In 30 patients after myocardial infarctum with actual silent ischemia (no pain
      during last 12 months) mononitrate (Olicard 40) was administered and red blood
      cell deformability was determined. Clinical improvement and decrease of
      aforementioned deformability were observed after mononitrate therapy.

PMID- 10907023
TI  - [Estimation of iron status in women in the course of gestation and delivery].
AB  - The triple examinations have taken in the course of gestation on 86 pregnant
      women living in Lodz. The determinations of HGB, HCT, RBC, MCV, MCH, MCHC, RDW,
      SF, TIBC, SI, TS, ST, and EP in the venous blood were made between 8-14 hbt, 22
      24 hbt, 32-35 hbt and at the first phase of the delivery. Among the examined
      women it was state the decrease of the value of hematological and iron indexes
      during the testified to the depletion of the reserved, transport and functional
      iron store in the organism of the pregnant women. The multiple criteria models
      were applied to diagnose the prevalence of different stages of iron deficiency
      with or without anemia in our pregnant women. For women in all trimesters of
      pregnancy the prevalence of iron deficiency and iron deficiency anemia was 38% in
      first and 54% in second half of pregnancy.

PMID- 10907024
TI  - [Hormonal replacement therapy and body weight in postmenopausal women].
AB  - Prospective studies that included 116 postmenopausal women on hormonal
      replacement therapy (transdermal estradiol and medroxyprogesterone acetate
      orally) was performed. Body mass index (BMI), total cholesterol concentration,
      levels of HDL and LDL-cholesterol were measured before and after 6 and 12 months
      of continuous treatment. Body mass index revealed no changes during one year of
      therapy. HDL-cholesterol significantly increased (p < 0.05) and LDL-cholesterol
      was significantly decreased after 6 and 12 months of HRT.

PMID- 10907025
TI  - [Antithrombin III activity in blood of patients with renal cancer].
AB  - The activity of antithrombin III (AT III) in the blood of 20 patients with renal
      carcinoma was examined. An increase of AT III activity in comparison with control
      group was observed. The increase of AT III activity in the blood of the patients
      with renal carcinoma can be as a result of compensatory mechanism safing these
      patients before thromboembolic complication. The measurement of AT III in renal
      carcinoma can be a prognostic symptom of haemorrhagic and thromboembolic
      complications.

PMID- 10907026
TI  - [The activity of protein C in the blood of patients with bladder carcinoma].
AB  - The activity of Protein C in the blood of patients with bladder carcinoma was
      examined. The average of Protein C activity was similar both in bladder carcinoma
      and in control group. The disperse of Protein C activity in bladder carcinoma was
      more greater than in control. In two patients with bladder carcinoma the bleeding
      with low activity of Protein C was observed. The low activity of Protein C in the
      blood of patients with bladder carcinoma can be the symptoms of an increased risk
      of thromboembolic complications.

PMID- 10907027
TI  - [The activity of alpha-2 macroglobulin in the blood of patients with prostatic
      carcinoma].
AB  - The activity of alpha 2-macroglobulin in the blood of the patients with prostatic
      carcinoma (PC) and benign prostatic hyperplasia (BPH) was examined. It was shown
      an decrease of alpha 2-macroglobulin in patients with prostatic carcinoma in
      comparison with control group consisted of the patients with benign prostatic
      hyperplasia. The low activity of alpha 2-macroglobulin in the blood od the
      patients with PC can be a symptom of an increase risk of haemorrhagic
      complications.

PMID- 10907029
TI  - [Hypercoagulation in patients with nephrotic syndrome].
AB  - Hypercoagulation and thrombotic complications associated with nephrotic syndrome
      (NS) are known from many years. However pathomechanism of those disturbances is
      not very clear. The aim of the presented study was to determine the role of
      platelets in hypercoagulation phenomenon in NS patients. Studies were carried out
      in 15 patients with NS in the course of chronic glomerulonephritis and 15 healthy
      volunteers. Following parameters were estimated: prothrombin, time APTT,
      fibrinogen, FDP, plasminogen, antithrombin III, alpha 2-antiplasmin and using
      Technicon H1 autoanalyser: platelet count (PLT), mean platelet volume (MPV) and
      PLT Mode. Additionally platelets aggregation (spontaneous and after collagen,
      epinephrine, ADP) was measured using Apact (Labor) aggregometer. We observed in
      patients with NS: a) decrease of AT III, b) slight increase (not significant) of
      fibrinogen, c) decrease of MPV and Mode PLT, d) increased spontaneous aggregation
      and sensitivity to aggregating agents. Our results suggest that: 1.
      Pathomechanism of hypercoagulation in NS is multifactorial. 2. Changes in
      morphology and function of platelets could be one of the factor playing important
      role in this mechanism.

PMID- 10907028
TI  - [Uremic middle molecules in chronic renal insufficiency].
AB  - In patients with chronic glomerulonephritis the level of uremic middle molecules
      was determined in relation to a degree of activity and a cause of disease. The
      increase of uremic middle molecules was connected with the degree of renal
      destruction.

PMID- 10907030
TI  - [Tissue plasminogen activator antigen (t-PA Ag) and tissue plasminogen activator
      inhibitor (PAI-1) in the course of hemodialysis in patients with chronic renal
      failure].
AB  - In 10 patients with chronic renal insufficiency we are tissue plasminogen
      activator antigen (t-PA Ag), tissue plasminogen activator inhibitor (PAI-1) and
      euglobulin lysis time (ELT) designed. This parameters are just before
      hemodialysis, in 60 minutes and 240 minutes after beginning of dialysis studied.
      In 60 minutes after the beginning of hemodialysis significant increased tissue
      plasminogen activator inhibitor antigen, decreased tissue plasminogen activator
      inhibitor activity and prolonged euglobulin lysis time. The observed increase in
      plasma t-PA antigen levels during hemodialysis is due to effects of extracorporal
      circulation on the fibrinolytic system. T-PA release and consequent consumption
      of tissue plasminogen activator inhibitor due to enhanced fibrinolytic activity
      during hemodialysis.

PMID- 10907032
TI  - [Changes in the sodium, potassium and lithium ion concentration in human
      epidermis in relation to death].
AB  - The concentrations of Na+, K+, Li+ have been assayed in the epidermis samples
      from 58 cadavers and 20 healthy individuals. The samples have been taken from the
      heels, and assayed with 2 flame photometers (Corning 480), using standard
      solutions supplied by the manufacturer. A concentration of Na+ and K+ in men
      exceeded the levels of these ions in women by two-fold. A level of Li+ is the
      same in both sexes and amounts to 2.8 mEq/kg. The Na+:K+ ratio in the epidermis
      of women and men is about 4:1. In the samples collected from cadavers, the
      difference in Na+ and K+ levels has been lower but Li+ level has been higher,
      amounting to 4.3 mEq/kg.

PMID- 10907031
TI  - [Use of low-molecular weight heparin during hemodialysis].
AB  - Coagulation parameters--platelet aggregation, beta-thromboglobulin,
      fibrinopeptide A were analyzes in patients with final chronic renal insufficiency
      during haemodialysis after a low molecular weight heparin application. In the
      study was documented that standard heparin is able to induce platelet
      aggregation. A low molecular weight heparin is suggested as sefex, because no
      influence on platelet aggregation was determined.

PMID- 10907034
TI  - [Antibiotic-resistant cystitis in the course of urinary bladder calculi after
      vesicoureteral reflux operation many years ago].
AB  - This is the introduction of chronic cystitis in course of urinary bladder
      calculi, 12 years after vesicoureteral reflux operation. The nucleus of the
      calculus (3 x 3 x 4 cm) were unresorbed dexon sutures left after the surgical
      treatment. Inaccuracy of radiological and ultrasonography examination delayed the
      settlement of the diagnosis about 18 months, and patient was caused of many
      months antibacterial therapy. After removal the calculus from the urinary
      bladder, dysuric disorders abated quickly and than after 8 weeks antibacterial
      therapy pathological changes in urine analysis disappeared, urine culture was
      sterile.

PMID- 10907033
TI  - [Mycology perirenal abscess as a complication of choledochoduodenal anastomosis
      due to stenosing papillitis].
AB  - This elaboration presents the seldom case of perirenal abscess insued after
      choledochoduodenoanastomosis. It refers to 71 years old patient, who was treated
      in General Hospital Biala Podlaska, Department of Surgery, with good results.
      Aetiology of that abscess is very seldom too, because it is concerned with
      Candida sp.

PMID- 10907035
TI  - [Angiofollicular lymph node hyperplasia (Castelman's disease) in an adult woman].
AB  - Angiofollicular lymph node hyperplasia Castleman's disease) is a rare disorder of
      unclear etiology and wide spectrum of systemic symptoms. This report describes a
      case of this disorder of hyalinovascular type in 45-years old woman. The lesions
      were localized in axillary lymph nodes. The disease was curable by surgical
      excision.

PMID- 10907036
TI  - [Ethylene glycol poisoning as a cause of chronic renal failure].
AB  - We showed some observations two Dialysis Centres concerning acute ethylene glycol
      poisoning and four cases of chronic renal failure progress. Renal biopsy at one
      patient and our clinical observations indicate for possibility of chronic renal
      failure development in some pts. We discussed hypotension of CRF development at
      those pts.

PMID- 10907037
TI  - [Diagnosis usefulness of beta-2 microglobulin in clinical practice].
AB  - The laboratory diagnostics is mostly based on proteins determination and this
      tendency has been developed lately. It especially concerns the determination of
      the low molecular weight proteins. One of them became beta 2-microglobulin (beta
      2-M), whose role in the organism and diagnostics is presently investigated. In
      this paper, the general characteristic of beta 2-M has been given including the
      usefulness in clinical diagnostics. A great part of this paper concerns role of
      this protein in nephrological diagnostics (early detection and localization of
      disorder, selective evaluation of filtration and resorption function, assessment
      of the degree of glomerules and tubules damage) and its significance in this
      field is without question. A very important problem is the determination of beta
      2-M both in serum and urine, giving full information about renal dysfunction. The
      usefulness of beta 2-microglobulin in diagnosing cancer also has been described
      and discussed, and this protein can be used as a relatively sensitive marker of
      treatment in selected leukaemias. A beta 2-M usefulness in diagnostics has been
      presented in other diseases too, but it is worthy to note that the value of this
      test presently is not fully appreciated by clinicians.

PMID- 10907038
TI  - [Fungal infections in heart transplant patient].
AB  - Considering imparied immunity in heart transplant patients as a result of
      immunosuppressive therapy, they are often exposed to the fungal infections. These
      infections are especially important because they still stay the main reason of
      death in transplant patients. Besides immunosuppressive therapy also antibiotics
      therapy, prolonged artificial ventilation of lungs, passed infections for example
      tuberculosis, or cytomegalovirus infection and Diabetes mellitus are the factors,
      which increase possibility of fungal infections in heart transplant patients.
      Fungal infections are the most often between first and sixth month after heart
      transplantation. They are caused mostly by species of Candida and Aspergillus
      fungi. Later than six months after heart transplantation also Cryptococcus fungi
      can develop fungal infection. The most often fungal infections in heart
      transplant patients is candidiasis. These kind of fungi colonize a skin and a
      mucose membrane and can very easy cause infection in friendly conditions.
      Infections caused by Aspergillus proceed as invasive aspergillosis, allergic,
      bronchopulmonary aspergillosis and aspergilloma. Depend on kind of infection we
      use pharmacologic or surgical therapy.

PMID- 10907039
TI  - [Importance of genetically determined acetylation of drugs and xenobiotics in
      pathogenesis of neoplasms].
AB  - A role of biomarker in determination of phenotype susceptibility to carcinogeus
      in environment may be connected with drug metabolism determined changes in drug
      metabolism is suggested as the most important in rational clinical therapy in
      neoplasmatic patients.

PMID- 10907040
TI  - [Homeopathy in therapy of bronchial asthma and other allergic diseases].

PMID- 10907041
TI  - Biology of Nitric Oxide, 6th International Meeting. Stockholm, Sweden, September
      5-8, 1999. Abstracts.

PMID- 10907043
TI  - Author and keyword Indexes, 1994-1998, volumes 1-5.

PMID- 10907042
TI  - 23rd Annual Meeting of the American Society of Primatologists, Denver, Colorado,
      USA., June 21-24, 2000. Abstracts.

PMID- 10907044
TI  - Low HDL in Cardiovascular Disease. Proceedings of an EAS Workshop. Istanbul,
      Turkey, September 24-25, 1999. Abstracts.

PMID- 10907045
TI  - Genetics and Atherosclerosis. Satellite Symposium of the XIIth International
      Symposium on Atherosclerosis. Aarhus, Denmark, June 22-24, 2000. Abstracts.

PMID- 10907046
TI  - 33rd Annual Meeting of the Society for the study of Reproduction. Madison,
      Wisconsin, USA., July 15-18, 2000. Abstracts.

PMID- 10907048
TI  - Author and keyword Indexes, 1998. Volumes 779-814.

PMID- 10907049
TI  - Annual Meeting of the Psychoneuroimmunology Research Society. Cape Fear
      Wilmington, North Carolina, USA., May 17-20, 2000. Abstracts.

PMID- 10907047
TI  - First International Conference on (Strept) Avidin Biotin Technologies. Alberta,
      Canada, June 18-21, 2000. Abstracts.

PMID- 10907050
TI  - 9th International Congress on Cardiovascular Pharmacotherapy. Salvador, Bahia,
      Brazil, March 26-30, 2000. Abstracts.

PMID- 10907052
TI  - ESCI 34th Annual Scientific Meeting. Aarhus, Denmark, May 17-20, 2000. Abstracts.

PMID- 10907051
TI  - 11th Annual Meeting of the European Academy of Childhood Disability. London,
      England, October, 1999. Abstracts.

PMID- 10907053
TI  - Author and keyword indexes, 1999. Volumes 363-385.

PMID- 10907054
TI  - ASGE Meeting, DDW. San Diego, California, USA., May 21-24, 2000. Abstracts.

PMID- 10907055
TI  - World Congress on In Vitro Biology. 2000 Meeting of the Society for In Vitro
      Biology. San Diego, California, USA. June 10-15, 2000. Abstracts.

PMID- 10907056
TI  - Proceedings of the 7th Bienniel Asia-Pacific Meeting on Impotence. Tokyo, Japan,
      October 26-30, 1999. Abstracts.

PMID- 10907057
TI  - 10th European Congress on Obesity (European Association for the Study of
      Obesity). Antwerp, Belgium, May 24-27, 2000. Abstracts.

PMID- 10907058
TI  - The 73rd Annual Meeting of the Japanese Pharmacological Society. Yokohama, Japan,
      March 23-25, 2000. Abstracts.

PMID- 10907060
TI  - 10th European Meeting on Hypertension. Goteborg, Sweden, May 29-June 3, 2000.
      Abstracts.

PMID- 10907059
TI  - The Proceedings of the 76th Annual Meeting of the Physiological Society of Japan.
      Nagasaki, Japan, March 28, 30, 1999. Abstracts.

PMID- 10907061
TI  - Xth National AINI Congress (Italian Neuroimmunology Association). Florence,
      Italy, November 15-16, 1999. Abstracts.

PMID- 10907062
TI  - 54th Annual Meeting of Canadian Society of Otolaryngology-Head and Neck Surgery.
      Toronto, Canada, May 28-31, 2000. Abstracts.

PMID- 10907063
TI  - 4th European Congress of Oto-Rhino-Laryngology, Head and Neck Surgery. Berlin,
      Germany, May 13-18, 2000. Abstracts.

PMID- 10907064
TI  - IXth ISLS 2000 Luminescence Symposium. Montpellier, France, May 15-17, 2000.
      Abstracts.

PMID- 10907065
TI  - First International Conference on Biology, Chemistry, and Therapeutic
      Applications of Nitric Oxide. San Francisco, California, USA., June 3-7,2000.
      Abstracts.

PMID- 10907066
TI  - VIth Mediterranean Ophthalmological Society Congress. VIth Michaelson Symposium
      on Ocular Circulation and Neovascularization. Jerusalem, Israel, May 21-26, 2000.
      Abstracts.

PMID- 10907067
TI  - 17th Nordic Congress of Cardiology, Reykjavik, Iceland, June 9-11, 1999.
      Abstracts.

PMID- 10907068
TI  - Detection of protein-protein interactions using a green fluorescent protein-based
      mammalian two-hybrid system.

PMID- 10907070
TI  - Contact printing of lift filters for alignment of plaque and colony lifts.

PMID- 10907069
TI  - Titration of infective and noninfective Ff filamentous bacteriophages using a
      monoclonal antibody against g3p.

PMID- 10907071
TI  - Wrapper arms strategy to construct multicomponent plasmids using three-piece
      ligation.

PMID- 10907072
TI  - DNase I activity retained after heat inactivation in standard buffer.

PMID- 10907073
TI  - Trypan blue as a slow migrating dye for SSCP detection in polyacrylamide gel
      electrophoresis.

PMID- 10907074
TI  - CEL I enzymatic mutation detection assay.

PMID- 10907075
TI  - Modified primers facilitate rapid screening of 16S rRNA gene libraries.

PMID- 10907076
TI  - Preparation of PCR-quality mouse genomic DNA with hot sodium hydroxide and tris
      (HotSHOT).

PMID- 10907077
TI  - Choice of microcentrifuge tubes influences T cell proliferation assay.

PMID- 10907078
TI  - Multiple sequence alignment tools on the Web.

PMID- 10907079
TI  - Scientific imaging with digital cameras.

PMID- 10907080
TI  - Analysis of DNA microarrays by non-destructive fluorescent staining using SYBR
      green II.
AB  - A simple, non-destructive procedure is described to determine the quality of DNA
      arrays before they are used. It consists of a preliminary staining step of the
      DNA microarray by using SYBR green II, a fluorophore with specific affinity for
      ssDNA, followed by a laser scan analysis. The surface quality, integrity and
      homogeneity of each DNA spot of the array can thus be assessed. After this
      preliminary control, which may avoid further analytical steps that lead to the
      waste of precious biological samples, a fully reversible staining procedure is
      performed that produces an array ready for subsequent use.

PMID- 10907081
TI  - Transmembrane motility assay of transiently transfected cells by fluorescent cell
      counting and luciferase measurement.
AB  - Current in vitro assays used in assessing tumor motility could be improved by the
      development of a simple technique that would facilitate studies of the impact of
      specific genes on pharmacologically altered chemotaxis. We developed a technique
      that improves on the classic transwell assay by using fluorescence and
      luminescence to assess chemotaxis. In this transient transfection system, co
      transfection of a reporter construct and a gene with an unknown impact on
      motility are coupled with biochemical assays to quantitate the number of cells
      that have received a transferred gene, which subsequently crosses the membrane.
      This assay was found to be less variable than the conventional transwell chamber
      and is easily adaptable to studies of cell motility or cell invasion. We also
      demonstrate that this assay can detect the effect of both genetic and
      pharmacological inhibition of motility alone and in combination. It therefore has
      the potential to reveal additive or synergistic effects.

PMID- 10907082
TI  - Quantification of enterovirus RNA in sludge samples using single tube real-time
      RT-PCR.
AB  - We have developed a quantitative RT-PCR method that can be used to determine the
      amount of enterovirus RNA in urban sludge samples. This method combines Taq-Man
      technology with the ABI Prism 7700 real-time sequence detection system. We
      optimized a one-step RT-PCR that uses a dual-labeled fluorogenic probe to
      quantify the 5' noncoding region of enteroviruses. For accurate quantification of
      the number of copies, a Mahoney type 1 poliovirus RNA standard was designed and
      produced using genetic engineering. This fragment, quantified using the Ribogreen
      method, was used in serial dilutions as an external standard. The method had a 7
      log dynamic range (5 to 2 x 10(7)). PCR inhibitors were removed by extracting
      viral RNA (after virus concentration) using the RNeasy mini kit with added
      polyvinylpyrrolidone (PVP) and running the amplification reaction with a mixture
      containing PVP and T4 gene 32 protein. This real-time quantification of
      enterovirus RNA allows large numbers of samples to be screened. Its sensitivity,
      simplicity and reproducibility render it suitable as a screening method with
      which to characterize enteroviruses, the presence of infectious particles being
      subsequently confirmed by cell culture.

PMID- 10907083
TI  - Sequence alterations can mask each other's presence during screening with SSCP or
      heteroduplex analysis: BRCA genes as examples.
AB  - For mutation detection, various screening techniques are widely used because DNA
      sequencing, the gold-standard method, is still considered to be expensive and
      laborious for high-throughput screening. Single-strand conformation polymorphism
      (SSCP) analysis, heteroduplex analysis (HA) and their variant techniques are
      popular and frequently used for this purpose. It is widely accepted that when
      searching for unknown sequence variations, any revealed distinct pattern should
      always be sequenced. We give examples here of the BRCA1 and BRCA2 genes where the
      SSCP/HA techniques can produce ambiguous predictions if used to detect known
      genetic variants compared to positive controls. Using direct DNA sequencing, we
      provide evidence that in such cases, mutations or polymorphisms can mask each
      other's presence. This phenomenon can often influence the results of any DNA
      testing because genetic variations such as single-nucleotide polymorphisms occur
      frequently in the human genome. We suggest that even in the case of known
      electrophoretic patterns of well-characterized genetic alterations, every
      sequence alteration should be confirmed by direct DNA sequencing, especially if
      genetic testing is carried out for diagnostic purposes.

PMID- 10907084
TI  - Color and graphic display (CGD): programs for multiple sequence alignment
      analysis in spreadsheet software.
AB  - Interpretation of multiple sequence alignments is of major interest for the
      prediction of functional and structural domains in proteins or for the
      organization of related sequences in families and subfamilies. However, a
      necessity for the bench scientist is the use of outstanding programs in a
      friendly computing environment. This paper describes Color and Graphic Display
      (CGD), a set of modules that runs as part of the Microsoft Excel spreadsheet to
      color and analyze multiple sequence alignments. Discussed here are the main
      functions of CGD and the use of the program to highlight residues of importance
      in a water channel family. Although CGD was created for protein sequences, most
      of the modules are compatible with DNA sequences.

PMID- 10907085
TI  - Fingerprinting method for phylogenetic classification and identification of
      microorganisms based on variation in 16S rRNA gene sequences.
AB  - The paper describes a method for the classification and identification of
      microorganisms based on variations in 16S rRNA sequences. The 16S rRNA is one of
      the most conserved molecules within a cell. The nature of the variable and spacer
      regions has been found to be specific to a given organism. Thus, the method
      presented here can be very useful for the classification and identification of
      microorganisms for which very little information is available. To automate the
      method, a comprehensive computer program called FPMAP has been developed for the
      analysis of restriction fragment pattern data. The method involves the
      restriction digestion of genomic DNA, preferably using four-cutters that may
      recognize 6-9 sites within the 16S rDNA. The fragments are separated on a
      polyacrylamide gel along with a suitable marker, then transferred into a nylon
      membrane and hybridized with a radiolabeled 16S rDNA probe. After
      autoradiography, the fragment sizes are calculated, and the data are analyzed
      using the FPMAP software. We demonstrate that the method can be used for
      identification of strains of Streptomyces and mycobacteria. The software is
      available from our ftp site ftp:?imtech.chd.nic.in/pub/com/fpmap/unix/.

PMID- 10907086
TI  - Software for quantitation and visualization of expression array data.
AB  - Software is described that facilitates the analysis of phosphoimages from large
      array hybridizations. The Macintosh PowerPC-compatible application and its manual
      are available at no charge from http:?people.bu.edu/strehlow. The software is
      compatible with both custom formats and array filters from three commercial
      manufacturers. It allows the rapid quantitation of every spot on images of
      hybridizations to large arrays. The user drags grids of squares over the spots on
      the image to define the coordinates of each spot, then aligns and edits the
      position of the grid. The software then corrects the positions as necessary and
      quantitates up to 27,000 spots per image. It stores the numerical values for each
      signal in a format called the fingerprint file. Fingerprint files can be directly
      averaged or compared, allowing the user to find mean values or differences in
      data from independent hybridization experiments. Data can be recalled from the
      fingerprint file and can be output in a variety of spreadsheet formats with
      several options for background correction. Finally, the software offers an output
      format that allows the convenient visualization of data points using animated,
      three-dimensional graphs.

PMID- 10907087
TI  - Virtual nitrogen tank to monitor frozen cell stocks.
AB  - We developed a program to facilitate the monitoring of biological samples (cell
      lines, sera, etc.) that are stored in liquid nitrogen containers. The program
      consists of a "virtual" container in which scientists can store their samples and
      a program that records the location of each sample, cell characteristics, storage
      dates, names of the manipulators and much more. Additional comments and a
      photograph can be associated with each vial, allowing for reliable tracking of
      samples. Vials can then be identified according to any parameter of interest to
      the scientist, including associated comments. Once identified, the program
      visually presents the location of these vials, which simplifies retrieving them
      from the real container. The program records the thawing of vials, along with the
      date and the name of the operator. Any academic laboratory requesting this
      standalone program will be granted a free license for its use.

PMID- 10907088
TI  - Antibody engineering at the millennium.
AB  - It has been almost 100 years since von Behring and Kitasato received the first
      Nobel prize for the discovery of passive immunotherapy and nearly 25 years since
      Kohler and Milstein first reported hybridoma technology. In the 15 years since
      Mullis and co-workers described PCR, a number of discoveries and technologies
      have converged to produce a renaissance in antibody therapeutics. Our vision of
      antibodies as tools for research--useful for the prevention, detection and
      treatment of disease--has been revolutionized by these recent advances. This
      review specifically focuses on what is now called antibody engineering and
      includes chimeric and humanized antibodies, immunoglobulin fragments, antibody
      libraries, antibody fusion proteins and transgenic organisms as bioreactors. As a
      consequence of refinements in antibody technology, the field of genetically
      engineered immunoglobulins has matured into an elegant and important drug and
      reagent development platform.

PMID- 10907089
TI  - The admid system: generation of recombinant adenoviruses by Tn7-mediated
      transposition in E. coli.
AB  - A new system has been developed for generating recombinant adenoviruses by Tn7
      mediated transposition in E. coli. Low copy number E. coli plasmids containing a
      full-length adenoviral genome with lacZattTn7 replacing E1 have been constructed.
      The adenovirus plasmid or admid, as well as high copy number progenitors, were
      stably maintained in E. coli strain DH10B. Several transfer vectors containing a
      mammalian expression cassette flanked by Tn7R and Tn7L were used as donors to
      transpose the mini-Tn7 into the E1 region of the adenoviral genome. Transposed
      recombinant admids are readily identified by their beta-galactosidase phenotype.
      Transfection of admid DNA into producer cells resulted in the efficient
      production of infectious adenovirus. This easy-to-use, efficient system generates
      pure, clonal stocks of recombinant adenovirus without successive rounds of plaque
      purification.

PMID- 10907090
TI  - Rapid colchicine competition-binding scintillation proximity assay using biotin
      labeled tubulin.
AB  - We have developed a rapid [3H]colchicine competition-binding scintillation
      proximity assay (SPA) to evaluate antimitotic compounds that bind to the
      colchicine-binding site on tubulin. The premise of our assay is that compounds
      will compete with radiolabeled colchicine for the tubulin-binding domain. Biotin
      labeled tubulin is incubated first with unlabeled compound and radiolabeled
      ligand. Streptavidin-labeled SPA beads are added, and the radiolabel associated
      with tubulin is directly counted with no separation steps. Under our experimental
      conditions, the dissociation constant of binding (Kd) for colchicine to tubulin
      was determined to be 1.4 microM, which was consistent with previously reported
      values. Assay validation was performed by competitively inhibiting [3H]colchicine
      binding to tubulin with known microtubule inhibitors and comparing their
      inhibition constants (Ki). Our SPA bead method is a powerful tool since it
      overcomes the disadvantage of traditional filtration techniques, as there are no
      separation steps. It is extremely easy to set up, multiple samples can be assayed
      and supply and labor costs are reduced because of the minimal volume and test
      reagents used.

PMID- 10907091
TI  - Method for cloning in vivo targets of the Egr-1 transcription factor.
AB  - A methodology is described that allows the in vivo trapping of transcription
      factors to their target regulatory elements in multiple genes simultaneously.
      Cross-linking using formaldehyde is the first of several steps to isolate,
      purify, clone and characterize multiple gene promoter DNA fragments. The example
      that we use indicates that the TGF beta 1 gene is a direct target induced by Egr
      1 in HT1080 cells that express constitutive Egr-1, thus explaining the growth
      retardation that follows Egr-1 expression. The genes identified using this
      procedure reflect the specific activities of Egr-1 at that moment in the cell and
      provide a method for confirmation of genes that are the direct targets of Egr-1
      action.

PMID- 10907092
TI  - Cell-based, high-content screen for receptor internalization, recycling and
      intracellular trafficking.
AB  - A variety of physiologically important receptors are internalized and then
      recycled back to the plasma membrane by the endocytic recycling compartment.
      These include the transferrin receptor and many G-protein coupled receptors
      (GPCRs). The internalization of GPCRs is a result of agonist stimulation. A cell
      based fluorescent imaging assay is described that detects and quantifies the
      presence of fluorescently labeled receptors and macromolecules in the recycling
      compartment. This High Content Screening application is conducted on the
      ArrayScan II System that includes fluorescent reagents, imaging instrumentation
      and the informatics tools necessary to screen for compounds that affect receptor
      internalization, recycling and GPCR activation. We demonstrate the Receptor
      Internalization and Trafficking application by quantifying (i) the
      internalization and recycling of the transferrin receptor using a fluorescently
      labeled ligand and (ii) the internalization of a physiologically functional model
      GPCR, a GFP-parathyroid hormone receptor chimera. These assays give high signal
      to-noise ratios, broad dynamic ranges between stimulated and unstimulated
      conditions and low variability across different screening runs. Thus, the
      Receptor Internalization and Trafficking application, in conjunction with the
      ArrayScan II System, forms the basis of a robust, information-rich and automated
      screen for GPCR activation.

PMID- 10907093
TI  - Willingness to participate in industrial protest: exploring social identification
      in context.
AB  - This study examines the impact of group identification and social context on
      willingness to participate in industrial protest. Trade union members (N = 313)
      completed a survey indicating their willingness to participate in union
      activities, their perceptions of the union and its role, and their attitudes
      toward present and former governments. Three independent conditions defined the
      union and its activities in different ways: either (a) referring to conflict with
      the present government, (b) referring to this conflict together with the
      government's threat to the union, or (c) presenting no additional information (a
      control condition). Results indicated that participants who identified highly
      with the union were more willing to participate in collective action to the
      extent that issues were defined in conflictual terms. Low identifiers resiled
      from participation in union activities when reference was made to conflict alone,
      but this effect was attenuated when reference was also made to threat. Results
      suggest that collective action is not simply a product of identification, but is
      also shaped by the distinct meaning which such action assumes for high and low
      identifiers within a given context.

PMID- 10907094
TI  - Thinking about Russia: plausible pasts and probable futures.
AB  - This paper uses both correlational and experimental methods to explore the power
      of counterfactual cognitions about the past to constrain judgments about the
      future as well as policy preferences. Study 1 asked 47 specialists on the Soviet
      Union to assess both the plausibility of controversial counterfactuals and the
      probability of controversial conditional forecasts. The results reveal deep
      ideological schisms, with liberals much more likely than conservatives to believe
      that Stalinism was not inevitable, that the Cold War could have ended earlier,
      and that Gorbachev might have succeeded in democratizing the Soviet Union if he
      had been a better tactician, among others. Reactions to these counterfactuals
      proved to be highly predictive of positions that experts in early 1992 endorsed
      concerning the advisability of 'shock therapy', expanding NATO eastward, and
      economic aid to Russia. Study 2 manipulated the salience and plausibility of
      counterfactual scenarios concerning (a) why the Cold War ended as it did, and (b)
      how close the US and USSR came to nuclear war. Changes in the counterfactual
      scenarios that non-experts endorsed produced significant changes in their policy
      preferences in the direction suggested by the salient counterfactual. Experts,
      however, were unswayed, often generating counter-arguments against dissonant
      counterfactuals. Taken together, the studies show that assumptions about what
      happened in the missing control conditions of history are highly subjective,
      largely theory-driven and profoundly consequential.

PMID- 10907095
TI  - Attitudes and attraction: a new test of the attraction, repulsion and similarity
      dissimilarity asymmetry hypotheses.
AB  - Dissimilarity and similarity between attitudes of the participants and a stranger
      were manipulated across two sets of issues to test the attraction, repulsion and
      similarity-dissimilarity asymmetry hypotheses. Participants (N = 192) judged
      social (liking, enjoyment of company) and intellectual (intelligence, general
      knowledge) attractiveness of the stranger. The similarity in the first set of
      attitudes x similarity in the second set of attitudes effect emerged in social
      attraction, but not in intellectual attraction. Stated simply, dissimilarity had
      a greater weight than similarity in social attraction, but equal weight in
      intellectual attraction. These results support the similarity-dissimilarity
      asymmetry hypothesis that predicts dissimilarity-repulsion to be stronger than
      similarity-attraction. However, they reject (1) the attraction hypothesis that
      dissimilarity and similarity produce equal and opposite effects on social
      attraction; and (2) the repulsion hypothesis that only dissimilar attitudes
      affect social attraction by leading to repulsion. An equal weighting of
      dissimilarity and similarity in intellectual attraction further suggested that
      the similarity-dissimilarity asymmetry on social attraction is reflective of a
      stronger avoidance response in the Darwinian sense.

PMID- 10907096
TI  - Self-evaluation maintenance in a larger social context.
AB  - Two studies extended Tesser's (1988) Self-evaluation Maintenance (SEM) model to
      include two close others and to examine the implications of intermediate
      performances on self-definition. Both demonstrated that when outperformed by both
      close others, participants rated activities low in self-relevance. When
      participants outperformed both close others, relevance was moderate or high. When
      participants were superior to one close other, but inferior to the other,
      relevance was low or moderate. When participants were uncertain about relative
      performances, and when there was disagreement over relative performances among
      the two close others and participants, ratings of relevance were attenuated as a
      means of protecting participants' self-evaluations. Results are discussed in
      terms of the importance of extending the SEM model to the larger social network.

PMID- 10907097
TI  - Among friends? An examination of friendship and the self-serving bias.
AB  - Do friends bound each other's self-enhancement tendencies? Do friends display the
      self-serving bias (SSB; i.e. taking individual credit for success but blaming a
      partner for failure)? Dyads consisting of either friends or strangers engaged in
      an interdependent-outcomes creativity test, received bogus success or failure
      feedback at the dyadic level, and made responsibility attributions for the joint
      test performance. Strangers displayed the SSB. Friends, in contrast, refrained
      from the SSB: they shared responsibility for both successful and unsuccessful
      test outcomes. Friendship does place boundaries on self-enhancement.

PMID- 10907098
TI  - The motivated tactician's juggling act: compatible vs. incompatible impression
      goals.
AB  - This study examines how perceivers negotiate multiple, and sometimes
      incompatible, impression formation goals. Previous research typically presents
      perceivers with a single impression goal (e.g. accuracy, supporting preferred
      beliefs), and does not consider how perceivers juggle multiple goals. The
      processes of perceivers with multiple compatible goals should show uncomplicated
      impression formation processes, that is, strategic use of particular target
      attributes (e.g. negative) that suit their purposes. Perceivers with incompatible
      goals, in contrast, should be less selective, and form more complex impressions
      that reflect all types of attributes. In this experiment, perceivers with
      compatible goals paid less attention to target attributes, systematically biased
      their interpretation of those attributes, and ultimately formed less complex
      impressions than individuals with incompatible goals. How multiple impression
      goals are prioritized is discussed.

PMID- 10907099
TI  - Social identity and the true believer: responses to threatened self-stereotypes
      among the intrinsically religious.
AB  - That religion is an impactful social category has often been assumed but seldom
      tested. Based on social identity and self-categorization theories, it is argued
      that devout religious commitment reflects, at least in part, an individual's
      motivation to engage in religious self-stereotyping (i.e. to perceive oneself as
      an exemplary religious group member). In order to test this analysis, individuals
      scoring high or low on a measure of intrinsic religious orientation received
      false feedback that either threatened or bolstered their self-perceptions on a
      dimension of behaviour that was either important or not important to religious
      group membership. As expected, intrinsic orientation predicted increased
      religious self-stereotyping only when feedback was threatening and important to
      religious group membership; affective and behavioural indices revealed a similar
      pattern. Implications for the social identity/self-categorization literature, and
      for theory development in the psychology of religion, are subsequently discussed.

PMID- 10907100
TI  - The primacy of self-referent information in perceptions of social consensus.
AB  - People's own responses to a social stimulus (i.e. whether they endorse it or
      reject it) predict how they expect other people to respond (consensus estimates).
      This correlation has long been accepted as evidence for social projection. There
      has been little direct evidence, however, for the assumption that self-referent
      judgments shape judgments about others. Supporting the projection model, Expt 1
      shows that self-referent information is more accessible than consensus estimates.
      Once they have been made, people's own endorsements and rejections of a stimulus
      facilitate consensus estimates. In turn, consensus estimates facilitate
      endorsements (but less so). Judgments about the physical properties of the
      stimulus facilitate neither type of social judgment. Supporting the view that
      projection is egocentric, Expt 2 shows that, when making consensus estimates,
      people rely more on their own endorsements than on the endorsements made by
      another individual. This self-other difference does not depend on whose
      endorsements are revealed first or on whether the other person is anonymous or
      individual.

PMID- 10907101
TI  - Leadership behaviour similarity as a basis of selection into a management team.
AB  - There are contexts where, in order to be effective, a management team needs to
      display different leadership behaviours as well as possessing a wide range of
      experiences and skills. But achieving heterogeneity of behaviours is difficult if
      there are behavioural-similarity biases affecting a selection process. A sample
      of 126 participants completed a simulation of a selection process for a
      management team. They compared selection criteria and chose either a task or
      relations-oriented applicant for an advertised position as well as reporting
      their perception of their own preferred leadership style. The results of the
      simulation indicate that leadership behaviour can be a basis for similarity
      attraction in the selection of a management team.

PMID- 10907102
TI  - Comments on 'Sex differences in beliefs about aggression: opponent's sex and the
      form of aggression' by J. Archer and A. Haigh.

PMID- 10907103
TI  - The story of the murine antiendothelial monoclonal antibody BGM. From patients'
      bedside to laboratory bench and from animal models to patients.

PMID- 10907104
TI  - Fc-gamma receptor reactivity in nonorgan-specific autoimmune diseases.

PMID- 10907106
TI  - Contributions of antibody VH domains to anti-DNA autoreactivity.

PMID- 10907105
TI  - Multiple genes/multiple autoantigens role in type 1 diabetes.

PMID- 10907107
TI  - Hidden autoantibodies.

PMID- 10907108
TI  - Tissue-associated autoantigens in rheumatoid arthritis. Tissue-antigens detected
      by autoantibodies in synovial fluid and sera of RA patients.

PMID- 10907109
TI  - Autoimmunity in atherosclerosis. The role of autoantigens.

PMID- 10907111
TI  - Fibrillin-1 protein in tight skin mice and scleroderma.

PMID- 10907110
TI  - Autoimmunity. Thoughts for the millennium.

PMID- 10907112
TI  - Islet amyloid polypeptide in the islets of Langerhans: friend or foe?
AB  - Islet amyloid polypeptide (IAPP), or amylin, was originally discovered as the
      constituent peptide in amyloid occurring in human insulinomas and in pancreatic
      islets in human subjects with Type II (non-insulin-dependent) diabetes mellitus.
      Its normal expression in beta cells and its co-secretion with insulin in response
      to nutrient stimuli, suggest a metabolic function for the peptide. Specifically,
      IAPP has most frequently been shown to inhibit insulin secretion, implying that
      IAPP has a role in the regulation of islet hormone homeostasis. The physiological
      significance of IAPP in islets has been difficult to assess; very high IAPP
      concentrations are required to alter insulin secretion. Moreover, until recently,
      IAPP receptors have not been characterised at the molecular level, thus leaving
      the actual target cells for IAPP unidentified. Furthermore, in experimental
      diabetes in rodents, the ratio of IAPP expression to that of insulin invariably
      is increased. In view of the pleiotropic effects attributed to IAPP, such
      regulation could be both adverse and beneficial in diabetes. Metabolic
      characterisation of mice carrying a null mutation in the IAPP gene or which
      overexpress IAPP in beta cells have recently confirmed that IAPP is a
      physiological inhibitor of insulin secretion. Based on experiments in which IAPP
      deficient mice develop a more severe form of alloxan-induced diabetes, we argue
      that the action of IAPP in the islets normally is beneficial for beta-cell
      function and survival; thus, the established up regulation of IAPP expression
      compared with that of insulin in experimental rodent diabetes could serve to
      protect islets under metabolically challenging circumstances.

PMID- 10907113
TI  - Sleep apnoea in children with diabetes mellitus: effect of glycaemic control.
AB  - AIMS/HYPOTHESIS: Patients with diabetes mellitus commonly have cardiovascular
      autonomic dysfunction and an abnormal ventilatory pattern during sleep. Few data
      are available on these changes in childhood diabetes. We investigated whether
      young diabetic children with or without diabetic neuropathy have ventilatory
      dysfunction during sleep and if so, whether these autonomic changes are related
      to the duration of diabetes and glycaemic control. METHODS: We studied 25
      children with insulin-dependent diabetes mellitus (19 boys, mean age 7.72 +/-
      1.99 years). All patients were insulin-dependent at diagnosis; blood samples for
      HbA1c assay were collected on the morning before testing and at 3-month intervals
      during the preceding year. Patients and control subjects (20 age-matched healthy
      children, 15 boys) underwent overnight polysomnography. RESULTS: More diabetic
      patients than control subjects had sleep apnoeas (p = 0.006); apnoeas in patients
      also lasted longer (p = 0.07). Patients with poorly controlled diabetes had more
      apnoeas than patients with well-controlled diabetes and than healthy control
      subjects (p < 0.0001). Respiratory events during sleep correlated significantly
      with glycaemic control (r = 0.360; p = 0.09) and with the duration of diabetes (r
      = 0.430; p = 0.04). CONCLUSION/INTERPRETATION: We conclude that respiratory
      control is compromised very early in children with diabetes. These anomalies are
      closely related to the duration of diabetes and to glycaemic control. In young
      children with diabetes, screening of ventilatory control using recording
      techniques that are simpler than polysomnography could provide an early
      indication that an adverse cardiopulmonary reaction has begun.

PMID- 10907114
TI  - Triglycerides, apo C3 and Lp B:C3 and cardiovascular risk in type II diabetes.
AB  - AIMS/HYPOTHESIS: Cardiovascular complications and particularly coronary heart
      disease are the main causes of morbidity and mortality in Type II (non-insulin
      dependent) diabetes mellitus. Some studies have shown that hypertriglyceridaemia
      in diabetes is an independent cardiovascular risk factor. In the ECTIM study high
      apolipoprotein C3 and lipoprotein B:C3 concentrations (lipoparticles playing a
      role in triglyceride metabolism) were associated with myocardial infarction in
      non-diabetic subjects. METHODS: We studied the relations between macroangiopathy
      and different cardiovascular risk factors and lipid variables in 188 Type II
      diabetic subjects. RESULTS: Multivariate analysis showed that triglycerides, apo
      C3 and Lp B:C3, sex, duration of diabetes, microalbuminuria and age were
      independently associated with macroangiopathy. The study group was divided into
      quartiles according to apo C3 and Lp B:C3 concentrations: the prevalence of
      macroangiopathy and coronary heart disease were increased in upper quartiles.
      CONCLUSION/INTERPRETATION: Triglycerides apo C3 and Lp B:C3 were independent
      cardiovascular risk markers in our group of Type II diabetic patients.

PMID- 10907115
TI  - Increased fetal leptin in type I diabetes mellitus pregnancies complicated by
      chronic hypoxia.
AB  - AIMS/HYPOTHESIS: The purpose of this study was to examine whether fetal leptin
      concentration correlates with severity of chronic or subchronic fetal hypoxia as
      indicated by increased fetal concentrations of erythropoietin in fetuses of
      mothers with Type I (insulin dependent) diabetes mellitus. METHODS: We measured
      leptin and erythropoietin concentrations in cord plasma and amniotic fluid with
      radioimmunoassay in 25 pregnancies (gestational age 37.2 +/- 1.0 weeks). Fetuses
      with amniotic fluid erythropoietin over 22.5 mU/ml were classified as hypoxic (n
      = 9) and those with amniotic fluid erythropoietin below 22.5 mU/ml (n = 16) as
      non-hypoxic. RESULTS: The hypoxic fetuses had significantly higher cord leptin
      concentrations than non-hypoxic fetuses (median 36.8; range, 12.5-135.1 vs median
      16.2; range, 3.7-52.2 micrograms/l), (p = 0.0066). Cord plasma leptin (n = 25)
      correlated directly with amniotic fluid erythropoietin (r = 0.727, p = 0.0001),
      with cord plasma erythropoietin (r = 0.644, p = 0.0005) and with the maternal
      last trimester HbA1C (r = 0.612, p = 0.0019) and negatively with cord artery pO2
      (r = -0.440, p = 0.032), and pH (r = -0.414, p = 0.040).
      CONCLUSION/INTERPRETATION: Fetal leptin concentrations increased concomitantly
      with erythropoietin during chronic or subchronic hypoxia. This phenomenon could
      indicate a role for leptin in fetal adaptation to hypoxia.

PMID- 10907116
TI  - Effects of size at birth, gestational age and early growth in preterm infants on
      glucose and insulin concentrations at 9-12 years.
AB  - AIMS/HYPOTHESIS: To test the hypothesis that small size for gestation and poor
      postnatal growth in preterm infants is associated with higher fasting and post
      load plasma glucose and insulin concentrations at 9-12 years of age. METHODS:
      Prospective follow-up at 9-12 years of 385 preterm children with birth weight
      less than 1850 g, who had anthropometry recorded at birth, 18 months and 7 years.
      Fasting plasma glucose, insulin, proinsulin and 32.33 split proinsulin
      concentrations and glucose and insulin concentrations 30 min after a standard
      glucose load were measured. RESULTS: Post-load glucose concentrations were
      negatively related to birth weight, independently of gestation or subsequent
      growth. Fasting split proinsulin and 30-min insulin concentrations were highest
      in children who showed the greatest increase in weight centile between birth and
      current follow-up, regardless of gestation. When weight during childhood was
      included, birthweight centile was, however, no longer statistically significant:
      concentrations of fasting, split, proinsulin and 30-min insulin were highest in
      those children who had shown the greatest increase in weight centile between 18
      months of age and current follow-up, with no evidence of a greater effect in
      those who were smallest at 18 months. CONCLUSION/INTERPRETATION: Our findings
      suggest that fetal growth influences plasma glucose 30 min after a glucose load
      in preterm children at 9-12 years. In contrast, childhood weight gain is the most
      important factor influencing insulin concentrations and this effect is the same
      regardless of early size.

PMID- 10907117
TI  - Adenovirus-mediated expression of a naturally occurring Asp905Tyr variant of the
      glycogen-associated regulatory subunit of protein phosphatase-1 in L6 myotubes.
AB  - AIMS/HYPOTHESIS: The glycogen-associated protein phosphatase-1 (PP1G) is thought
      to play an important part in the regulation of skeletal muscle glycogen content.
      We have previously identified an Asp905Tyr polymorphism of the glycogen
      associated regulatory subunit of the protein phosphatase 1 (PPP1R3) gene which
      among healthy subjects was associated with decreased insulin stimulated non
      oxidative glucose metabolism, i.e. primary glycogen synthesis. In this study, the
      functional effect of the polymorphism was examined in vitro. METHODS: Wild type
      (PPP1R3-Asp905) and mutant (PPP1R3-Tyr905) PPP1R3 were expressed in L6 myotubes
      using adenovirus-mediated gene transfer. Basal and insulin-stimulated glucose
      uptake and glycogen synthesis were measured. Furthermore, the sensitivity of
      glycogen synthesis to a cyclic AMP agonist was measured. RESULTS: Compared with
      green fluorescent protein-transduced myotubes and non-transduced myotubes,
      overexpression of PPP1R3-Asp905 and PPP1R3-Tyr905 increased both basal and
      insulin-stimulated glycogen synthesis approximately twofold. Treatment of both
      non-transduced and PPP1R3-transduced L6 myotubes with a cAMP agonist decreased
      both basal and insulin-stimulated glycogen synthesis by about 40%. Overexpression
      of PPP1R3 did not affect either basal or insulin-stimulated 2-deoxy-D-glucose
      uptake compared with green fluorescent protein-transduced cells.
      CONCLUSION/INTERPRETATION: Results obtained from L6 myotubes transduced with
      PPP1R3-Asp905 or PPP1R3-Tyr905 showed no statistically significant difference.
      Therefore, the Asp905Tyr variant alone is unlikely to account for the decreased
      insulin stimulated non-oxidative glucose metabolism observed in the human study
      reported previously.

PMID- 10907118
TI  - A potent diazoxide analogue activating ATP-sensitive K+ channels and inhibiting
      insulin release.
AB  - AIMS/HYPOTHESIS: To characterise the effects of BPDZ 73 (7-chloro-3
      isopropylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide), a newly synthesised
      diazoxide analogue, on insulin secretory cells. METHODS: Measurements of 86Rb,
      45Ca outflow, membrane potential, [Ca2+]i, insulin release in secretory cells as
      well as measurements of smooth muscle contractile activity and glycaemia were
      carried out. RESULTS: The analogue BPDZ 73 induced a dose-dependent decrease in
      insulin output. The IC50 value averaged 0.73 +/- 0.05 mumol/l. The drug increased
      the rate of 86Rb (42K substitute) outflow from perifused rat pancreatic islets.
      This effect was inhibited by glibenclamide, a KATP channel blocker. Measurements
      of DiBAC4(3) fluorescence further indicated that BPDZ 73 hyperpolarised the
      insulin secreting cells. It also decreased 45Ca outflow from pancreatic islets
      perifused throughout in the presence of 16.7 mmol/l glucose and extracellular
      Ca2+. By contrast, the drug did not affect the increase in 45Ca outflow mediated
      by K+ depolarisation. In single beta cells, BPDZ 73 inhibited the glucose-induced
      but not the K(+)-induced rise in [Ca2+]i. Moreover, in Wistar rats, i.p.
      injection of BPDZ 73 provoked a considerable increase in blood glucose
      concentration whereas diazoxide induced a modest rise in glycaemia. Lastly, the
      vasorelaxant properties of BPDZ 73 were slightly less pronounced than those of
      diazoxide. CONCLUSION/INTERPRETATION: The inhibitory effect of BPDZ 73 on the
      insulin-releasing process results from the activation of KATP channels with
      subsequent decrease in Ca2+ inflow and [Ca2+]i. The drug seems to be a KATP
      channel opener, more potent and more selective than diazoxide for insulin
      secreting cells.

PMID- 10907119
TI  - Brain function rescue effect of lactate following hypoglycaemia is not an
      adaptation process in both normal and type I diabetic subjects.
AB  - AIMS/HYPOTHESIS: We have previously shown that lactate protects brain function
      during insulin-induced hypoglycaemia. An adaptation process could, however, not
      be excluded because the blood lactate increase preceded hypoglycaemia. METHODS:
      We studied seven healthy volunteers and seven patients with Type I (insulin
      dependent) diabetes mellitus with a hyperinsulinaemic (1.5 mU.kg-1.min-1)
      stepwise hypoglycaemic clamp (4.8 to 3.6, 3.0 and 2.8 mmol/l) with and without Na
      lactate infusion (30 mumol.kg-1.min-1) given after initiation of hypoglycaemic
      symptoms. RESULTS: The glucose threshold for epinephrine response was similar
      (control subjects 3.2 +/- 0.1 vs 3.2 +/- 0.1, diabetic patients = 3.5 +/- 0.1 vs
      3.5 +/- 0.1 mmol/l) in both studies. The magnitude of the response was, however,
      blunted by lactate infusion (AUC; control subjects 65 +/- 28 vs 314 +/- 55
      nmol/l/180 min, zenith = 2.6 +/- 0.5 vs 4.8 +/- 0.7 nmol/l, p < 0.05; diabetic
      patients = 102 +/- 14 vs 205 +/- 40 nmol/l/180 min, zenith = 1.4 +/- 0.4 vs 3.2
      +/- 0.3 nmol/l, p < 0.01). The glucose threshold for symptoms was also similar (C
      = autonomic 3.0 +/- 0.1 vs 3.0 +/- 0.1, neuroglycopenic = 2.8 +/- 0.1 vs 2.9 +/-
      0.1 mmol/l, D = autonomic 3.2 +/- 0.1 vs 3.2 +/- 0.1, neuroglycopenic 3.1 +/- 0.1
      vs 3.2 +/- 0.1 mmol/l) but peak responses were significantly attenuated by
      lactate (score at 160 min C = 2.6 +/- 1 vs 8.8 +/- 1, and 0.4 +/- 0.4 vs 4.8 +/-
      1, respectively; p = 0.02-0.01, D = 1.3 +/- 0.5 vs 6.3 +/- 1.7, and 2.3 +/- 0.6
      vs 5.7 +/- 1.1 p = 0.07-0.02). Cognitive function deteriorated in both studies at
      similar glucose thresholds (C = 3.1 +/- 0.1 vs 3.0 +/- 0.1, D = 3.2 +/- 0.1 vs
      3.3 +/- 0.2 mmol/l). Although in normal subjects a much smaller impairment was
      observed with lactate infusion (delta four-choice reaction time at 160 min = 22
      +/- 12 vs 77 +/- 31 ms; p = 0.02), in Type I diabetic patients lactate infusion
      was associated with an improvement in cognitive dysfunction (0.2 +/- 0.4 vs -38
      +/- 0.2 delta ms, p = 0.0001). CONCLUSION/INTERPRETATION: A blood lactate
      increase after the development of hypoglycaemic symptoms reduces
      counterregulatory and symptomatic responses to insulin-induced hypoglycaemia and
      favours brain function rescue both in normal and diabetic subjects. These
      findings confirm that lactate is an alternative substrate to glucose for cerebral
      metabolism under hypoglycaemic conditions.

PMID- 10907120
TI  - Th1-like dominance in high-risk first-degree relatives of type I diabetic
      patients.
AB  - AIMS/HYPOTHESIS: The humoral part of the immune system, including autoantibodies,
      is known to predict manifest Type I (insulin-dependent) diabetes mellitus in
      first-degree relatives but the cell-mediated immune process preceding the
      manifest disease still is not known. The aim of this investigation was to
      estimate the immunological balance of Th-like lymphocytes (Th1/Th2) in high-risk
      first-degree relatives of Type I diabetic children. METHODS: Peripheral blood
      mononuclear cells (PBMC) from 21 healthy high-risk first-degree relatives (ICA >
      or = 20) were examined and compared with the response seen in PBMC from children
      with newly diagnosed Type I diabetes and healthy control subjects of similar age,
      sex and HLA-type. Expression of interleukin-4 (IL-4) and interferon-gamma (IFN
      gamma) mRNA were determined by RT-PCR and as protein by ELISPOT after stimulation
      with specific epitopes of GAD65 (a.a. 247-279, 509-528, 524-543), bovine serum
      albumin, the ABBOS peptide (a.a. 152-169) and insulin. RESULTS: High-risk
      relatives had a high ratio of IFN-gamma:IL-4 compared with both diabetic children
      (p = 0.0005) and healthy control subjects (p = 0.004). Production of IFN-gamma
      seen in high-risk relatives was negatively correlated to production of GADA (r = 
      0.44, p = 0.05). The high concentration of IFN-gamma from high-risk relatives,
      decreased after stimulation with peptides of GAD65, the ABBOS peptide, BSA and
      insulin. Increased secretion of IL-4 was observed after stimulation with two
      peptides of GAD65 (a.a. 509-528 and 524-543), the ABBOS peptide and insulin.
      CONCLUSION/INTERPRETATION: Overwhelming production of IFN-gamma seen in
      peripheral blood mononuclear cells from high-risk first-degree relatives of
      children with Type I diabetes suggests a Th1-like immune deviation in the
      prediabetic phase.

PMID- 10907121
TI  - Cross-reactive rubella virus and glutamic acid decarboxylase (65 and 67) protein
      determinants recognised by T cells of patients with type I diabetes mellitus.
AB  - AIMS/HYPOTHESIS: To examine the cross-reaction between viral and beta-cell
      protein determinants and to further understand the potential role of this
      mechanism in Type I (insuline-dependent) diabetes mellitus. METHODS: Immune
      responses to a panel of 28 viral and beta-cell protein peptides representing
      selected sequences of rubella virus (RV), Coxsackie virus, human 38 KDa31G and
      glutamic acid decarboxylase (GAD 65 and 67) proteins in proliferation or
      cytotoxicity assays have been studied using uncloned and cloned T-cell cohorts
      from a group of 60 Type I diabetic patients. RESULTS: Peptide GAD65(252-266)
      induced the responses of patients with recent onset diabetes in proliferation
      assays at the highest frequency (77%), whereas GAD67(212-226) stimulated the
      cellular responses at the highest rate (61%) in patients with late-onset
      diabetes. RVE1(157-176) was recognised by all groups of patients at the highest
      frequency and the largest amplitude among the viral peptides tested. T-cell
      clones specific to GAD65(252-266), GAD65(274-286) or GAD67(212-226) were tested
      in cytotoxicity assays for their responses to rubella virus peptides. Each of
      these T-cell clones cross-reacted with two to four rubella virus peptides,
      including RVE1(157-176) and RVE2(87-107). Analysis of the sequences of cross
      reactive viral and glutamic acid decarboxylase antigens showed that these
      epitopes shared similar peptide binding motifs to HLA DR3/DR4. There is a
      statistically significant correlation between the response amplitude of patient's
      peripheral blood mononuclear cells to RVE1(157-176), RVE2(87-107) and GAD65(274
      286) in patients with recent onset diabetes, and to RVE1(157-176) and GAD67(212
      226) in patients with late onset diabetes. CONCLUSION/INTERPRETATION: Cross
      reactive glutamic acid decarboxylase and rubella virus determinants identified by
      T-cell clones were also recognised at high frequencies by general T-cell
      populations of Type I diabetic patients.

PMID- 10907122
TI  - Effects of diabetes and hypoxia on gene markers of angiogenesis (HGF, cMET, uPA
      and uPAR, TGF-alpha, TGF-beta, bFGF and Vimentin) in cultured and transplanted
      rat islets.
AB  - AIMS/HYPOTHESIS: The vascularisation of newly transplanted islets originates from
      the recipients. Because islets transplanted into a diabetic do less well than
      those transplanted into a euglycaemic environment, we examined the hypothesis
      that gene expression of angiogenic factors in grafts is delayed in diabetes.
      These factors include hepatocyte growth factor (HGF) and its receptor c-MET, and
      urokinase plasminogen activator (uPA) and its receptor uPAR, basic fibroblast
      growth factor (bFGF), TGF-alpha and TGF beta-1. METHODS: Isolated rat islets were
      studied in vitro under normoxic and hypoxic culture conditions and gene
      expression was determined with semi-quantitative multiplex RT-PCR. We found that
      HGF but not c-MET expression was induced by hypoxia in vitro. Using syngeneic
      Lewis rats, gene expression was also studied in grafts on days 1, 3, 5, 7 and 14
      after transplantation. RESULTS: In grafts of normoglycaemic rats, HGF expression
      was enhanced on day 3 and maintained whereas expression of c-MET fell and
      remained down until day 14. Expression of uPA was up at day 3 and remained high;
      expression of uPAR was also up at day 3 but then fell to control levels at day
      14. Expression of bFGF, TGF-alpha and TGF beta-1 persisted throughout. Vimentin,
      a marker of fibroblasts, had increased expression at day 1 which was further
      enhanced in subsequent days. In the grafts of diabetic recipients the expression
      of HGF, uPA and uPAR were delayed, being clearly expressed at day 5 rather than
      day 3. Vimentin expression was similarly delayed. CONCLUSION/INTERPRETATION: This
      apparent delay in angiogenesis provides a potential mechanism for the less
      favourable outcomes of islets transplanted into diabetic recipients.

PMID- 10907123
TI  - Changes in the density and localisation of endothelin receptors in the early
      stages of rat diabetic retinopathy and the effect of insulin treatment.
AB  - AIMS/HYPOTHESIS: The endothelin system (ET system) has been implicated in the
      retinal blood flow abnormalities that precede the onset of diabetic retinopathy.
      This study was undertaken to assess whether the density and localisation of both
      the immunoreactive endothelin-1 and endothelin receptors in rat retina change in
      the early stages of diabetes and the insulin treatment would affect those
      changes. METHODS: Untreated streptozotocin-diabetic, insulin-treated
      streptozotocin-diabetic and age-matched control rats were killed 15, 45 and 90
      days after the induction of diabetes. Binding assays were used to determine the
      density and proportion of endothelin receptors in neural retinal membranes.
      Localisation of endothelin receptors and immunoreactive endothelin-1 were
      analysed by microautoradiography and immunohistochemistry, respectively. RESULTS:
      Fifteen days after the induction of diabetes, the neural retinal membranes of
      untreated streptozotocin-diabetic rats showed a statistically significant
      decrease in the density of both endothelin receptor subtypes when compared with
      age-matched control rats. At 90 days, however, the density of endothelin
      receptors type B was statistically significantly higher than that of control
      rats, and the innermost layers of the diabetic retina also showed an increase of
      both endothelin receptor type B receptor and immunoreactive endothelin-1 signal.
      Insulin treatment during 90 days up-regulated endothelin receptor type A in
      neural retinal membranes and in the innermost layers of the retina when compared
      with control retinas. CONCLUSION/INTERPRETATION: These results show that the
      endothelin system is altered in both vascular and neuronal components of the
      retina in early diabetic retinopathy. The up-regulation of endothelin receptor
      type A induced by insulin treatment suggests that insulin might be involved in
      retinal microangiopathy.

PMID- 10907124
TI  - A comparison of diabetic polyneuropathy in type II diabetic BBZDR/Wor rats and in
      type I diabetic BB/Wor rats.
AB  - AIMS/HYPOTHESIS: To examine the functional, metabolic and structural
      abnormalities in peripheral nerve in the spontaneously Type II (non-insulin
      dependent) diabetic BBZDR/Wor rat and compare these data with those in the Type I
      (insulin-dependent) diabetic BB/Wor rat. METHODS: Animals were examined at 6 and
      14 months of diabetes. Nerve conduction velocity was measured longitudinally.
      Nerve polyols were analysed using gas liquid chromatography and Na/K(+)-ATPase
      activity was measured enzymatically. Light and electron microscopic techniques
      were used for nerve morphometry. RESULTS: Diabetic BBZDR/Wor rats showed a slowly
      progressive nerve conduction defect that reached 17% (p < 0.01) at 14 months.
      There was a decrease in Na+/K(+)-ATPase of 35% (p < 0.05). Structurally, there
      were mild myelinated fibre atrophy (p < 0.05), mild or absent changes of the node
      of Ranvier, but significant (p < 0.001) segmental demyelination and Wallerian
      degeneration. These findings point to a more severe nerve conduction defect,
      severe myelinated fibre atrophy and profound nodal changes in Type I
      spontaneously diabetic BB/Wor rats maintained at the same hyperglycaemic
      concentrations. CONCLUSION/INTERPRETATION: We conclude that other factors, beside
      hyperglycaemia, are involved in the pathogenesis of the more severe Type I
      diabetic neuropathy which possibly involve insulin and C-peptide deficiencies.

PMID- 10907125
TI  - Lack of synergism between long-term poor glycaemic control and three gene
      polymorphisms of the renin angiotensin system on risk of developing diabetic
      nephropathy in type I diabetic patients.
AB  - AIMS/HYPOTHESIS: Reports on a putative synergism between poor glycaemic control
      and carriage of the angiotensin II type 1 receptor (AGTR1) C1166-allele and risk
      of diabetic nephropathy have been conflicting. Therefore, we investigated the
      interaction between long-term glycaemic control and three polymorphisms in the
      genes coding for AGTR1 (A1166-->C), angiotensin converting enzyme (ACE/ID) and
      angiotensinogen (M235T) on risk of developing diabetic nephropathy. Furthermore,
      we investigated the relation between a random measurement and long-term
      measurements of haemoglobin A1c (HbA1c). METHODS: We studied Caucasian patients
      with Type I (insulin-dependent) diabetes mellitus and nephropathy (120 men 74
      women, age 41.1 +/- 9.6 years, diabetes duration 28 +/- 8 years) and long
      standing Type I diabetic patients with persistent normoalbuminuria (112 men 69
      women, age 42.5 +/- 10.0 years, diabetes duration 27 +/- 9 years). Genotyping was
      PCR-based and metabolic control estimated from all measurements of HbA1c done in
      each patient [average (range) n = 31 (6-74)]. The median observation time (range)
      was 13.5 (2-14) years. RESULTS: Type I diabetic patients with a history of poor
      glycaemic control (HbA1c above the median, 8.7%) had an increased risk of
      diabetic nephropathy compared with patients with a better metabolic control, OR
      (95% CI): 9.2 (5.8-14.7). The magnitude of this risk was similar in carriers and
      non-carriers of the mutations. The risk of nephropathy in patients with HbA1c
      above compared with below the median in carriers of the mutant C1166-allele, D
      allele, or T235-allele were 7.6 (95% CI: 3.9-14.8), 10.4 (6.0-17.8) and 9.8 (5.4
      17.9), respectively. A significant correlation (r = 0.74, p < 0.001) existed
      between a random and long-term measurements of HbA1c with a small mean difference
      (limits of agreement) [0.2 (-1.8 to 2.1)%] between the two estimates.
      CONCLUSION/INTERPRETATION: Poor metabolic control is a major risk factor for
      diabetic nephropathy in Caucasian Type I diabetic patients. This risk was similar
      in carriers and non-carriers of the mutant alleles of the AGTR1 (A1166-->C),
      ACE/ID and angiotensinogen-M235T polymorphisms. The HbA1c value measured at
      random reflects rather closely average long-term HbA1c values.

PMID- 10907126
TI  - Complete molecular scanning of the human Fas gene: mutational analysis and
      linkage studies in families with type I diabetes mellitus. The Danish Study Group
      of Diabetes in Childhood and The Danish IDDM Epidemiology and Genetics Group.
AB  - AIMS/HYPOTHESIS: The human Fas gene (FAS) on chromosome 10q24.1 encoding a cell
      surface receptor involved in apoptosis was evaluated as a candidate
      susceptibility gene for Type I (insulin-dependent) diabetes mellitus. Apoptosis
      mediated by Fas is important in maintaining peripheral self-tolerance and in down
      regulating the immune response and could have a role in immune-mediated beta-cell
      destruction. METHODS: We did a molecular scan of the entire human FAS (promoter,
      exons 1-9 including exon-intron boundaries and the 3'UTR) using single strand
      conformational polymorphism-heteroduplex analysis. RESULTS: We identified 15
      mutations, of which 11 are new. Of these a g-1194A-->T and a g-295Ains give rise
      to alterations of transcription-factor-binding consensus sequences for c-Myb, SP
      1 and NF-kappa B, respectively. A total of 1068 people from a Danish family
      collection comprising 138 Type I diabetic sib-pair families (289 affected and 121
      unaffected offspring) and 103 Type I diabetic parent-offspring multiplex families
      (103 affected and 112 unaffected offspring) were typed for the three most
      frequent polymorphisms with high heterozygosity indices and for a FAS
      microsatellite. Haplotypes were established and data analysed using the extended
      transmission disequilibrium test, ETDT. CONCLUSION/INTERPRETATION: We found no
      overall evidence for linkage of the FAS polymorphisms to Type I diabetes. We
      conclude that it is unlikely that the Fas gene does contribute to genetic
      susceptibility for Type I diabetes.

PMID- 10907127
TI  - A sustained, non-insulin related, hypoglycaemic effect of electroacupuncture in
      diabetic Psammomys obesus.
AB  - AIM/HYPOTHESIS: Electroacupuncture has been shown to induce a short-term
      hypoglycaemic effect in streptozotocin diabetic rats. We designed an experiment
      to investigate the effect of electroacupuncture in Psammomys obesus, a model of
      insulin resistance and non-insulin-dependent diabetes mellitus. METHODS: We
      divided 29 diabetic Psammomys randomly into three groups: abdominal
      electroacupuncture (real, n = 11), back electroacupuncture (placebo, n = 9) and
      control (anaesthesia, n = 9). Electroacupuncture was carried out on days 1, 3 and
      5 of the experiment. During the first week of the experiment, blood glucose was
      tested three times on treatment days and once on the following days. Over the
      next 2 weeks, blood glucose was tested every other day. Animals were weighed at
      the same time of blood sampling. After 3 weeks, at the end of the experiment,
      blood was drawn for measurement of insulin, fructosamine, cholesterol and
      triglycerides. RESULTS: At day 5 (end of intervention), blood glucose (as per
      cent of primary concentrations, means +/- SE) was 57 +/- 10, 93 +/- 13 and 89 +/-
      11 for the real, placebo and control groups respectively (p = 0.02). At day 8,
      blood glucose 68 +/- 14, 86 +/- 16 and 97 +/- 9 for the real, placebo and control
      groups respectively (p = 0.04). At day 22, blood glucose was 79 +/- 11, 85 +/- 15
      and 131 +/- 2 for the real, placebo and control groups (p = 0.04). Comparison of
      the decline in blood glucose, throughout the 3 weeks, between the real and
      placebo groups by ANOVA was highly significant (p < 0.0001), the difference
      between the placebo and control groups at the same time was not significant (p >
      0.05). Animal weight gain, serum insulin, fructosamine, cholesterol and
      triglycerides were not significantly different between real and placebo groups.
      CONCLUSION/INTERPRETATION: Electroacupuncture at special abdominal acupoints
      induces a sustained hypoglycaemic effect in diabetic Psammomys compared with
      electroacupuncture at non-specific points, without weight loss. No
      hypoinsulinaemic effect was shown in the real and placebo groups.

PMID- 10907128
TI  - Troglitazone decreases serum uric acid concentrations in type II diabetic
      patients and non-diabetics.

PMID- 10907129
TI  - Antibodies to tissue transglutaminase C in newly diagnosed and long-standing type
      I diabetes mellitus.

PMID- 10907130
TI  - Nature or nurture: an insightful illustration from a Chinese family with
      hepatocyte nuclear factor-1 alpha diabetes (MODY3)

PMID- 10907132
TI  - T-cell markers in type I diabetes: progress, prospects and realistic
      expectations.

PMID- 10907131
TI  - A simple test for the high-frequency P291fsinsC mutation in the HNF1 alpha/MODY3
      gene.

PMID- 10907133
TI  - Genetic analysis of infectious salmon anaemia virus (ISAV) from Scotland.
AB  - The nucleotide sequences of segments 2 and 8 of infectious salmon anaemia virus
      (ISAV) isolates from Scotland were determined. These were used to predict amino
      acid sequences of the products of these segments. The sequences were compared
      with those previously published for ISAV from Norway and North America.
      Nucleotide and amino acid variations were found in the Scottish isolate,
      indicating that it is not identical to those Norwegian or North American strains.
      Although phylogenetic analysis of the sequences was not possible, it was clear
      that the Scottish isolate is more closely related to the Norwegian strain than
      the North American. Sequencing further isolates that are geographically or
      temporally separated will be important in advancing understanding of the
      epidemiology of this important disease.

PMID- 10907134
TI  - A new bacterial white spot syndrome (BWSS) in cultured tiger shrimp Penaeus
      monodon and its comparison with white spot syndrome (WSS) caused by virus.
AB  - This paper describes a new bacterial white spot syndrome (BWSS) in cultured tiger
      shrimp Penaeus monodon. The affected shrimp showed white spots similar to those
      caused by white spot syndrome virus (WSSV), but the shrimp remained active and
      grew normally without significant mortalities. The study revealed no evidence of
      WSSV infection using electron microscopy, histopathology and nested polymerase
      chain reaction. Electron microscopy indicated bacteria associated with white spot
      formation, and with degeneration and discoloration of the cuticle as a result of
      erosion of the epicuticle and underlying cuticular layers. Grossly the white
      spots in BWSS and WSS look similar but showed different profiles under wet mount
      microscopy. The bacterial white spots were lichen-like, having perforated centers
      unlike the melanized dots in WSSV-induced white spots. Bacteriological
      examination showed that the dominant isolate in the lesions was Bacillus
      subtilis. The occurrence of BWSS may be associated with the regular use of
      probiotics containing B. subtilis in shrimp ponds. The externally induced white
      spot lesions were localized at the integumental tissues, i.e., cuticle and
      epidermis, and connective tissues. Damage to the deeper tissues was limited. The
      BWS lesions are non-fatal in the absence of other complications and are usually
      shed through molting.

PMID- 10907135
TI  - Monitoring Piscirickettsia salmonis by denaturant gel electrophoresis and
      competitive PCR.
AB  - Reported strains of Piscirickettsia salmonis, a pathogen of salmonid fishes, were
      analyzed by amplifying part of the internal transcribed spacer (ITS) of the
      ribosomal RNA (rRNA) operon followed by denaturing gradient gel electrophoresis
      (DGGE) of the amplicons. All amplified fragments differing in sequence were
      distinguished by migration during DGGE. A simpler format, constant denaturant gel
      electrophoresis (CDGE), allowed the same diagnostic distinctions among strains.
      Sampling during 1997 and 1998 of salmonids from 5 different sites on and near
      Chiloe Island in southern Chile displaying piscirickettsiosis revealed only P.
      salmonis resembling LF-89, the type strain first isolated in 1989. These
      observations are encouraging for control strategies, which might otherwise be
      compromised by unpredictable shifts of P. salmonis types in salmon farms. A
      competitive PCR assay offered insight about the power of PCR for quantification
      and about specific tissue invasiveness by this intracellular pathogen. This
      approach revealed that the PCR could amplify approximately 1 to 10 P. salmonis
      genome equivalents against a background of > 99.9% salmonid DNA. It also raised
      the possibility that the salmonid brain is an important site for P. salmonis
      survival, with its bacterial load in 1 individual having been about 100 times the
      loads observed in liver and kidney. Pathogen detection by competitive PCR in a
      surface seawater sample from a netpen in use indicated a density of about 3000 to
      4000 P. salmonis cells (or their DNA remnants) 1(-1). Such quantitative estimates
      should aid decisions about disease prevention and management as, for example,
      choice of netpen sites following fallow periods and certification of ova, which
      are known conduits of infection.

PMID- 10907136
TI  - Ichthyophonus irregularis sp. nov. from the yellowtail flounder Limanda
      ferruginea from the Nova Scotia shelf.
AB  - A previously described unusual form of the protistan parasite Ichthyophonus,
      differing in morphological and developmental features from I. hoferi sensu Plehn
      & Mulsow, was recovered from yellowtail flounder Limanda ferruginea Storer from
      the Brown's Bank area of the Nova Scotia shelf. The nuclear gene encoding the
      rRNA of the small ribosomal subunit was amplified from this unusual form of
      Ichthyophonus using the polymerase chain reaction, sequenced and aligned with
      other eukaryote small subunit (ssu)-rDNAs. Inferred phylogenetic trees clearly
      show that its ssu-rDNA is distinct from those of 2 isolates of I. hoferi sensu
      Plehn & Mulsow from different hosts and geographical locations (herring in the
      North Sea, and yellowtail flounder from the Nova Scotia shelf). We consider the
      unusual form to be a separate species, I. irregularis. The occurrence of a
      second, distinct type of Ichthyophonus within a single host species raises the
      possibility that ichthyophoniasis could be produced by different (although
      related) pathogens, and in some cases, by concurrent infections of the two.

PMID- 10907137
TI  - Plasma and bile antibodies of the teleost Trematomus bernacchii specific for the
      nematode Pseudoterranova decipiens.
AB  - We investigated the occurrence of antibodies against protein antigens of the
      nematode parasite Pseudoterranova decipiens in the plasma and bile of the
      Antarctic teleost Trematomus bernacchii. Three different P. decipiens protein
      solutions were prepared: excreted/secreted proteins from live larvae (ESP);
      surface-associated proteins obtained by mild extraction of larval bodies (SAP);
      and cuticular soluble proteins recovered by extraction in strong reducing
      conditions (CSP). Using different immunoassays, these 3 preparations were tested
      for their ability to bind fish antibody. As determined by ELISA, the specific
      antibody binding activity was higher in SAP than in CSP. As determined by dot
      blot immunoassay, the specific antigen binding activity versus SAP was higher in
      bile than in plasma antibodies. A different number of antigenic components of SAP
      and ESP were identified by immunoblotting performed with plasma or bile
      antibodies. These results led to the conclusion that T. bernacchii parasitism by
      nematodes involves plasma and bile anti-parasite antibodies. Furthermore bile
      antibodies were found to be more reactive and more heterogeneous than plasma.

PMID- 10907139
TI  - Spatial and temporal variation of trematode infection in coexisting populations
      of intertidal gastropods Littorina saxatilis and L. obtusata in the White Sea.
AB  - Trematode infection was studied in sympatric populations of the periwinkles
      Littorina saxatilis and L. obtusata in 2 regions of Kandalaksha Bay of the White
      Sea to assess host-parasite interactions at the population level. Twenty-seven
      spatially separated populations were each surveyed in 1984-1994; 2 heavily
      infected populations were investigated annually over a 16 yr period. Ten
      trematode species were found in the periwinkle populations. The closest
      association in spatial distribution and temporal dynamics was observed between 3
      ecologically and morphologically similar trematodes of the 'pygmaeus' group:
      Microphallus piriformes, M. pygmaeus and M. pseudopygmaeus. For these 3 species,
      the prevalences were closely associated in the 2 host species when spatially
      separated sites from the 2 studied regions were considered, while in the 2
      populations studied over the 16 yr period, a correlation was only observed
      between the infection levels of L. saxatilis and L. obtusata by either M.
      piriformes and immature microphallids. Likewise, within each host species,
      significant correlations were revealed between the prevalence of the different
      microphallids of the 'pygmaeus' groups. However, they were fewer and weaker when
      the long-term dynamics of infection in the 2 heavily infected populations were
      considered. Most other trematodes did not show significant association in
      prevalence either within or between the 2 host species on spatial and temporal
      scales.

PMID- 10907138
TI  - Changes in hydrolytic enzyme activities of naive Atlantic salmon Salmo salar skin
      mucus due to infection with the salmon louse Lepeophtheirus salmonis and cortisol
      implantation.
AB  - The changes in the activities of mucus hydrolytic enzymes and plasma cortisol
      levels were examined following infection of Atlantic salmon Salmo salar with the
      salmon louse Lepeophtheirus salmonis and these changes were compared with those
      resulting from elevated plasma cortisol. Salmon were infected at high (Trial 1;
      178 +/- 67) and low (Trial 2; 20 +/- 13) numbers of lice per fish and the
      activities of proteases, alkaline phosphatase, esterase and lysozyme in the
      mucus, as well as plasma cortisol levels were determined. At both levels of
      infection, there were significant increases of protease activity over time (1-way
      K-WANOVA; Trial 1, p = 0.004; Trial 2, p < 0.001). On several sampling days,
      generally on later days in the infections, the mucus protease activities of
      infected fish were significantly higher than control fish (Student's t-tests; p <
      0.05). In addition, zymography experiments demonstrated bands of proteases at 17
      to 22 kDa in the mucus of infected salmon that were absent in the mucus from non
      infected fish and absent in the plasma of salmon. The intensity of these protease
      bands increased in the mucus over the course of both infections. However, plasma
      cortisol levels were elevated only in the heavily infected fish from the first
      trial. At high infection levels (Trial 1), alkaline phosphatase activity was
      higher in the mucus of infected fish at all days (t-test, p < 0.05). However, at
      the lower infection level (Trial 2), the mucus alkaline phosphatase activity did
      not differ significantly between infected and non-infected fish. Esterase and
      lysozyme activities were very low and did not change with time nor between non
      infected and infected salmon in either challenge. Mucus enzyme activities of
      cortisol-implanted salmon did not change over time, nor were there any
      differences in activities between cortisol-implanted and control salmon. The
      present study demonstrates biochemical changes resulting from sea lice infection
      of Atlantic salmon occurring at the site of host-pathogen interaction, the mucus
      layer. However, the origin of these enzymes, whether host or pathogen, remains to
      be determined.

PMID- 10907140
TI  - A logistic regression of risk factors for disease occurrence on Asian shrimp
      farms.
AB  - Serious shrimp-disease outbreaks have reduced shrimp production and slowed
      industry growth since 1991. This paper tests factors such as farm sitting and
      design, and farm-management practices for relationships with disease occurrence.
      Logistic regression is used to analyze farm-level data from 3951 shrimp farms in
      13 Asian countries. Disease occurrence is modeled as a 0-1 variable where 1 =
      disease loss of > or = 20% to any 1 crop, and 0 = losses of < 20%. Logistic
      regression is performed for each of 3 levels of shrimp culture intensity, i.e.
      extensive, semi-intensive, and intensive. Attempts to apply logistic regression
      models to each country were not successful due to insufficient data for most
      countries. Factors affecting disease occurrences were quite different for
      different farming intensities. Farms that had larger pond production areas, with
      larger number of farms discharging effluent into their water supply canals, and
      removed silt had greater disease occurrence. On the other hand, farms that
      practiced polyculture and took water from the sea through a canal had lower
      disease occurrence.

PMID- 10907141
TI  - Aspects of general antimicrobial properties of skin secretions in the common seal
      Phoca vitulina.
AB  - Considerable amounts of several saccharide residues (alpha-D-Man, beta-D-GlcNAc,
      alpha-D-GalNAc, beta-D-Gal, alpha-D-Gal, alpha-L-Fuc, NeuNAc) are demonstrated by
      lectin histochemistry in the sections of the sebaceous glands, and, particularly,
      the apocrine tubular glands of the common seal. These sugars may be liberated on
      the skin surface by microbial activities and, then, represent a general
      antimicrobial protection mechanism of the skin because of their ability to
      inhibit the adherence of different bacteria and fungi to the epidermis.

PMID- 10907142
TI  - Occurrence of Bothriocephalus acheilognathi in cyprinid fish from three lakes in
      the flood plain of the Yangtze River, China.
AB  - Cyprinid fish, Hemiculter leucisculus, Cultrichthys erythropterus and Culter
      dabryi, were sampled from Liangzi, Honghu and Tangxun lakes in the flood plain of
      the Yangtze River. The cestode Bothriocephalus acheilognathi Yamaguti, 1934 was
      found in the 3 lakes, but C. erythropterus sampled from Liangzi lake was found
      uninfected due probably to the small sample size. Findings of the cestode in the
      3 lakes represent the first record of the parasite in the flood plain of the
      Yangtze River, indicating that B. acheilognathi may be distributed much wider in
      China than previously recognized.

PMID- 10907143
TI  - Family therapists, community, and civic renewal.
AB  - In this article, we review family therapy's history regarding community concerns
      and broader societal issues; offer a model of levels of therapists' involvement
      with communities and community systems; and propose that family therapists join
      the citizen activation movement by becoming catalytic partners with families in
      communities. We call for a new kind of community practice that is driven less by
      therapist-defined problems and professional expertise, and more by community
      defined problems and families' own expertise.

PMID- 10907144
TI  - Save the young--the elderly have lived their lives: ageism in marriage and family
      therapy.
AB  - The paucity of literature addressing mental health issues concerning geriatric
      populations represents the perpetuation of ageist practices and beliefs in the
      field of marriage and family therapy. The purpose of this study was to assess
      whether client age and clinical training relate to the evaluation of couples who
      present for conjoint therapy. Written vignettes describing two couples, one older
      and one younger, who report issues involving the absence of sexual intimacy,
      increased frequency of arguments, and increased use of alcohol were evaluated by
      practicing marriage and family therapists, therapists-in-training, and
      individuals with no clinical background. It was hypothesized that respondents'
      views would vary in connection with the age of the couple and with the three
      levels of participant training. Results indicate that client age and participant
      training are associated with perceptions of individual and couple functioning.
      Our findings suggest that the relational and mental health concerns experienced
      by elder couples are not perceived as seriously as are identical concerns
      experienced by younger couples. Contrary to our expectations the observed
      differences between views of the two age conditions did not significantly differ
      between levels of participant training. Training and experience in marriage and
      family therapy may not significantly mitigate vulnerability to age-discrepant
      views.

PMID- 10907145
TI  - Ethical decision making among family therapists and individual therapists.
AB  - In this study, we investigated the ethical decision making of 30 individual and
      30 family therapists in order to detect the types of decision making used by
      practicing therapists. Informants responded to three ethical dilemmas. Two of the
      situations were hypothetical. The third dilemma was a situation the informant had
      experienced in practice. Each interview was assessed for decision-making style,
      using content analysis. Kohlberg's justice reasoning and Gilligan's care
      reasoning provided the conceptual foundations for this analysis. The results
      suggest that both family and individual therapists prefer care reasoning on all
      dilemma types. There was significantly more care reasoning demonstrated on the
      personal dilemma than on the hypothetical dilemmas. Characteristics of informants
      did not provide clear explanations for the differences found in reasoning.

PMID- 10907146
TI  - The structure of interpretations in family therapy: a video-enhanced exploration.
AB  - A method for assessing the structure of interpretations of family therapy events
      is described. Family sessions were videotaped; each participant then
      independently reviewed the tape, stopping it to indicate any significant events
      and describing the importance of each identified sequence. Qualitative approaches
      to analyzing the stop points are described, using data from six families and
      their therapist. This combination of direct session experience and reflective
      interpretation provides a much-needed perspective on the meaning of sessions and
      psychotherapeutic interaction. Research and clinical implications for
      scientifically examining the structure of shared interpretations in family
      therapy are discussed.

PMID- 10907147
TI  - Rating scale of therapists' systemic responses in an individual treatment
      context.
AB  - This study involves the development of a process study instrument that measures
      therapists' systemic responses in an individual treatment context. The scale
      captures the quintessential elements of the family systems approach, namely,
      interventions that address interactional sequences of behaviors and contextual
      concerns. Two hundred and thirty sessions from 15 clients were rated using this
      scale. An interrater reliability of .62 was attained at the session level; at the
      client level, reliability reached an average of .89. Analyses with the 15 cases
      did not reveal a significant relationship between process variables and outcome
      measures. However, exploratory analysis of 11 clients, excluding cases that might
      have other overriding factors that impact treatment outcome, revealed significant
      findings confirming the predictive validity of the scale.

PMID- 10907148
TI  - Repeating the errors of our parents? Family-of-origin spouse violence and
      observed conflict management in engaged couples.
AB  - Based on a developmental social learning analysis, it was hypothesized that
      observing parental violence predisposes partners to difficulties in managing
      couple conflict. Seventy-one engaged couples were assessed on their observation
      of parental violence in their family of origin. All couples were videotaped
      discussing two areas of current relationship conflict, and their cognitions
      during the interactions were assessed using a video-mediated recall procedure.
      Couples in which the male partner reported observing parental violence (male
      exposed couples) showed more negative affect and communication during conflict
      discussions than couples in which neither partner reported observing parental
      violence (unexposed couples). Couples in which only the female partner reported
      observing parental violence (female-exposed couples) did not differ from
      unexposed couples in their affect or behavior. Female-exposed couples reported
      more negative cognitions than unexposed couples, but male-exposed couples did not
      differ from unexposed couples in their reported cognitions.

PMID- 10907149
TI  - Wife abuse and battering in the sociocultural context of Arab society.
AB  - Despite increasing public, professional, and scientific interest in the problem
      of wife abuse and battering, little has been written about the importance of
      sociocultural sensitivity in intervention with abused and battered women in Arab
      society. In this article, I describe central family values in that society and
      discuss their relevance to wife abuse and battering. Specifically, the discussion
      focuses on values such as mutual family support and interdependence, family
      reputation, women's inferiority and male supremacy, and family cohesion and the
      relevance of those values to wife abuse and battering. In addition, I present
      Arab women's perspectives on this problem, as revealed in their responses to open
      ended questions that were part of larger studies conducted by me. In this regard,
      five dimensions of their perspectives are considered: (1) Women's definitions of
      violence against women; (2) their awareness of the problem; (3) their
      justification or condemnation of violence against women; (4) their awareness of
      the risk encountered by battered women; and (5) their approach toward coping with
      the problem. The results are discussed from the perspective of the sociocultural
      context of Arab society. The article concludes with recommendations for
      socioculturally sensitive intervention with battered women in this society.

PMID- 10907150
TI  - "Lesbians, gay men, and their parents": a critique of LaSala and the prevailing
      clinical "wisdom".
AB  - This article challenges the popular assumption that coming out to family of
      origin is important for lesbians and gay men's mental health and couple
      relationships. First, I present theory emphasizing the unique position of
      lesbians/gays in families of origin and the significance of "families of choice."
      Second, I review the quantitative research on social support received by
      lesbians/gays from family of origin, friends, and other social network sources.
      Third, I demonstrate how the dominant clinical opinion about coming out to family
      is based on an unwarranted use of theory developed for heterosexuals and on
      overgeneralization of findings from studies of white, upper-middle-class, North
      American lesbians/gays. Fourth, I propose five determinants of lesbian/gay
      persons' decisions to come out to family-of-origin members. Fifth, I argue that
      such decisions are constrained by "realistic" costs/benefits in various
      sociocultural niches rather than being a simple function of individuals' levels
      of differentiation. Lastly, I offer an expanded contextual stance for the family
      therapist working with lesbian/gay clients.

PMID- 10907151
TI  - [Antibodies against tissue transglutaminase as a serological marker in dermatitis
      herpetiformis During].
AB  - Dermatitis herpetiformis is associated with celiac disease. IgA antibodies to
      endomysium are considered as sensitive and specific markers for celiac disease.
      Recently, tissue transglutaminase was identified as the antigen of anti
      endomysium antibodies. Moreover, serum levels of IgA antibodies to tissue
      transglutaminase were found to correlate with titers of IgA antibodies to
      endomysium in patients with both celiac disease and dermatitis herpetiformis.
      These findings confirm the close pathogenic relation between the two diseases.
      The determination of serum levels of antibodies to tissue transglutaminase may be
      a tool that can be routinely used for the diagnosis of dermatitis herpetiformis
      in the future.

PMID- 10907152
TI  - [The spectrum of cytotoxic lymphomas of the skin].
AB  - Cytotoxic lymphomas are peripheral T- and natural killer-cell lymphomas with
      primary or secondary skin manifestations. They constitute a heterogeneous group
      of lymphoproliferative disease. They are characterized by expression of cytotoxic
      proteins and are frequently associated with an aggressive clinical course. A
      brief introduction to cytotoxic lymphocytes and proteins is followed by a
      detailed description of clinical, histological, immunohistochemical and genetic
      characteristics of cutaneous cytotoxic lymphomas.

PMID- 10907153
TI  - [Skin changes in newborn infants in the first 5 days of life].
AB  - BACKGROUND AND OBJECTIVE: To prospectively survey skin lesions in a large group
      of newborns, as no such study has as yet been performed in Germany.
      PATIENTS/METHODS: In a prospective study, we examined one thousand newborn babies
      twelve to 120 hours old. RESULTS: In 59.7%, one or more skin lesions could be
      detected, some of which were only transient. Noticeable differences from other
      studies included a higher incidence of congenital melanocytic nevi (6%) and port
      wine stains (2.8%). Instead of the usual male:female ratio of 1:2 we found a 1:1
      ratio for port wine stains. Toxic erythema of the newborn and milia were less
      frequent than in other studies. CONCLUSIONS: With a frequency of 37.2%, vascular
      lesions such as nevus flammeus and hemangioma are the most common skin lesions in
      newborns. Our study found a higher incidence of congenital melanocytic nevi than
      reported in literature. An associated of skin lesions and maternal smoking during
      pregnancy was not detected.

PMID- 10907154
TI  - [Direct versus video-aided parent education in atopic eczema in childhood as a
      supplement to specialty physician treatment. A controlled pilot study].
AB  - BACKGROUND AND OBJECTIVE: Psychological problems in children and parents related
      to children's atopic eczema (AE) may impede the success of treatment. We studied
      the question, if behavior-based parental education in groups (DPE) or
      standardized video-education (VPE) could enhance dermatological treatment effects
      and reduce skin-damaging behaviors in children and stress in their mothers.
      PATIENTS/METHODS: 47 mothers attending the university outpatient-clinic for
      dermatology and their AE-children (mean age 4 years) participated in the study.
      18 mothers underwent the DPE (10 sessions), 15 mothers worked with VPE at home.
      Dermatological standard treatment (CG; N = 14) served as control for a 16-weeks
      evaluation-period. RESULTS: AE-symptoms improved overall, but the effectiveness
      of the treatments differed significantly, improval with parent education and was
      best with VPE. Psychological problems of mothers were equally reduced with DPE
      and VPE. CONCLUSIONS: It is suggested that VPE is a cost effective and less time
      consuming method for supporting dermatological therapy of AE in children.

PMID- 10907155
TI  - [Unresolved couple conflicts in male infertility].
AB  - BACKGROUND AND OBJECTIVE: There is empirical evidence that sterility causes a
      considerable amount of distress and affects correspondingly the partnership.
      Empirical results concerning male infertility show increased somatic complaints
      and reduced self-esteem of the men as well as a dominance of the accompanying
      partners. Which couple conflicts arise after the diagnosis of male infertility?
      PATIENTS/METHODS: 84 infertile men were examined with a partnership diagnostic
      questionnaire. The questionnaire was evaluated with regard to quantity and
      quality of unsolved couple conflicts. RESULTS: The results show that infertile
      men do not mention more unsolved conflict areas in their partnership than healthy
      men. If one looks qualitatively at the mentioned conflict areas, striking
      differences in comparison to the control group can be seen. CONCLUSIONS: In
      comparison to the control group of healthy men, the specificity of conflict areas
      in infertile couples can be best understood on the basis of exchange-theoretical
      considerations.

PMID- 10907156
TI  - [Successful management of systemic lupus erythematosus with IgM enriched
      immunoglobulins].
AB  - Systemic lupus erythematosus is a potentially life-threatening disease. Even the
      use of potent immunosuppressive drugs often barely controls the disease. In
      addition, treatment-related side effects are common due to the high doses of
      immunosuppressive drugs necessary. We report on two cases of acutely exacerbated
      systemic lupus erythematosus which were difficult to control with prednisone and
      cyclophosphamide. Both patients were additionally treated with IgM-enriched
      preparations of intravenous immunoglobulins. In both cases, the doses of the
      immunosuppressive drugs used could be significantly reduced. After nine treatment
      cycles, patients remained disease-free for a follow-up period of one year with
      only minimal immunosuppressive therapy. Our observation shows that IgM-enriched
      immunoglobulins can be used for therapy of systemic lupus erythematosus.

PMID- 10907157
TI  - [Unilateral eyelid swelling as an initial manifestation of angiosarcoma].
AB  - Cutaneous angiosarcomas mainly arise on the scalp and face of older patients.
      They present with reddish nodules or plaques and tend to bleed and ulcerate.
      Angiosarcomas show an aggressive and recurrent course and have a high potential
      for metastasis. We report on a 48-year-old patient with unilateral eyelid edema
      as the first manifestation of an angiosarcoma. The clinical presentation, the
      history of contact allergy, the presence of antinuclear antibodies, and abnormal
      thyroid function tests favoured a non-neoplastic disease. However, multiple
      biopsies confirmed the diagnosis of a highly differentiated angiosarcoma. Staging
      of the patient revealed no metastasis. After radical surgery including orbital
      exenteration and postoperative radiation therapy, no recurrence was observed with
      a follow up of 26 months. This case underlines the importance of including
      angiosarcoma in the differential diagnosis of unilateral eyelid edema.

PMID- 10907158
TI  - [Congenital manifestations of juvenile xanthogranuloma (large nodular form)].
AB  - An infant girl presented at birth with multiple, large nodular xanthogranulomas.
      Her monozygotic twin sister was not affected. The congenital tumors were up to
      1.5 cm in diameter, done-shaped and mainly located on the head and the upper half
      of the body. Histologically the cells were characterized as CD68+ non-Langerhans
      histiocytes. Follow-up for 18 months showed no new tumors and regression of the
      existing ones. No extra-cutaneous manifestations were observed. Knowledge of the
      differential diagnosis, especially the group of Langerhans cell histiocytosis, is
      essential for prognosis estimation.

PMID- 10907159
TI  - [Benign symmetrical Launois-Bensaude type II lipomatosis with market systemic
      involvement and psoriasis].
AB  - Benign symmetric lipomatosis of the pseudoathletic type was identified in a woman
      with a positive family history for the disorder and a past history of alcohol
      abuse. She had an exceptionally high number of additional diseases such as
      arthropathy with degenerative osteoporosis, hyperuricemia, hyperlipidemia,
      psoriasis, neuropathy, muscular atrophy, arteriosclerosis and increased
      cardiovascular risk factors.

PMID- 10907160
TI  - [Market hyperpigmentation in psoriatic plaque as a sequelae of combination
      therapy with UVB-311 and calcipotriol].
AB  - The combination of UVB phototherapy with topical application of vitamin D analogs
      is frequently used for treating psoriasis. This regimen is not only very
      effective but also has only minimal side effects. Pronounced, persistent
      hyperpigmentation developed in the psoriatic plaques in a patient who was treated
      with combined UVB (311 nm) radiation and topical calcipotriol.

PMID- 10907161
TI  - [Trigeminotrophic ulceration of the ala nasi in Wallenberg syndrome].
AB  - A patient developed a trophic ulceration of the nose after an acute bulbar
      ischemia with infarction of the right trigeminal nuclei. Neurologic examination
      showed symptoms of a Wallenberg syndrome including ipsilateral hyp- and
      paresthesia of the second trigeminal branch and disturbed sensibility and
      temperature sense on the contralateral half of the body. The right ala nasi
      showed the characteristic sickle-shaped defect (ulceration en arc). The
      differential diagnosis and therapeutic approaches are discussed.

PMID- 10907162
TI  - [Alternative medicine: really an alternative to academic medicine?].
AB  - Numerous courses on alternative medicine are regularly advertised in Deutsches
      Arzteblatt, the organ of the German Medical Association. The present German
      legislation likewise supports this form of medicine, and this explains why
      Iscador, an extract of the mistletoe, is found in the Rote Liste, a directory of
      commercially available medical drugs, under the heading "cytostatic and
      antimetastatic drugs" although such beneficial effect is unproven. To give
      another example, a German health insurance fund was sentenced to pay for
      acupuncture as a treatment for hepatic failure. This judgement is characteristic
      of the present German judicial system and represents a victory of "oracling
      irrationalism" (Popper). The astonishing popularity of alternative medicine can
      be explained by a revival of romanticism. An intellectually fair opposite
      position has been delineated by Karl Popper in the form of critical rationalism.
      It is important to realize, however, that our decision to adhere to rational
      thinking is made in the innermost depth of our heart but not on the basis of
      rational arguing. Rather, the decision in favor of reason has a moral dimension.

PMID- 10907163
TI  - [Latex allergy].

PMID- 10907164
TI  - [Letter from Cadiz. IX Jose Cabre Memorial Lecture].

PMID- 10907165
TI  - [Photodiagnostic tests. 2: Photoprovocation tests].

PMID- 10907166
TI  - Uterine adenomyomas excluding atypical polypoid adenomyomas and adenomyomas of
      endocervical type: a clinicopathologic study of 30 cases of an underemphasized
      lesion that may cause diagnostic problems with brief consideration of adenomyomas
      of other female genital tract sites.
AB  - We report 30 uterine tumors composed of an admixture of endometrioid glands,
      endometrioid stroma, and smooth muscle that lacked the characteristic features of
      atypical polypoid adenomyoma. The patients ranged from 26 to 64 (median 47) years
      of age. The usual presenting symptom was abnormal vaginal bleeding, which was
      "massive" in two patients. Six patients were treated by polypectomy only, with
      hysterectomy performed in the remainder. Twenty-seven adenomyomas were in the
      corpus (22 submucosal, two mural, and three subserosal) and three in the cervix.
      The subserosal and submucosal examples were polypoid. The tumors were 0.3 to 17
      cm in greatest dimension, and firm with cystic areas often present on sectioning.
      Focal hemorrhage was described in five cases. On microscopic examination, the
      tumors were composed of glands and cysts lined by endometrial-type epithelium
      separated by endometrial stroma and smooth muscle, with smooth muscle
      predominating. Minor foci of tubal-type epithelium (14 cases), mucinous
      endocervical-type epithelium (2 cases), and squamous epithelium (1 case) were
      present. The smooth muscle component was cellular in three cases and contained
      occasional bizarre nuclei in three cases. The epithelial cells were uniformly
      bland. No mitotic activity was observed in the epithelial or mesenchymal elements
      in 20 cases. In the remainder, up to 5 mitotic figures/10 high-power fields were
      observed in the epithelium (3 cases), the stroma and smooth muscle (3 cases), or
      both compartments (4 cases). Follow-up in 14 cases revealed no recurrence or
      extrauterine spread in any case. A diagnosis of adenocarcinoma or adenosarcoma
      was entertained by the submitting pathologist in five of 14 consultation cases.
      Adenomyomas are unusual benign uterine tumors that can be misdiagnosed, in part,
      because the lesion has not often received attention in the literature. The most
      realistic considerations in the differential diagnosis are atypical polypoid
      adenomyoma and adenosarcoma. The former, by definition, has epithelial atypia and
      the latter a malignant (usually low grade) stromal component with typically
      absent or inconspicuous smooth muscle. Distinction of adenomyoma from
      adenosarcoma may have significant therapeutic implications, particularly in young
      women.

PMID- 10907167
TI  - Simple hyperplasia of the endometrium: an evaluation of proliferative activity by
      Ki-67 immunostaining.
AB  - As endometrial hyperplasia has been characterized over the past 100 years, some
      investigators have questioned the hyperplastic nature of nonatrophic cystic
      glands associated with an increase in gland-to-stroma ratio, which is currently
      considered to represent simple endometrial hyperplasia. In the current study, the
      proliferative activity of simple endometrial hyperplasia was examined using an
      antibody to Ki-67 protein, a well-established marker of proliferative activity,
      and compared with the results of activity in inactive/atrophic endometrium,
      proliferative endometrium, and other forms of endometrial hyperplasia. In an
      evaluation of 68 endometrial biopsy specimens showing 110 histologic patterns,
      the mean Ki-67 index (percentage of Ki-67 positive nuclei) was 2.8% in
      inactive/atrophic endometrium, 23.2% in proliferative endometrium, 9.8% in simple
      hyperplasia, 12.7% in complex hyperplasia, and 10% in atypical complex
      hyperplasia. In simple hyperplasias, the mean Ki-67 index was 3.9% in dilated
      glands without infolding or outbranching, 14.6% in nondilated glands showing
      outbranching or slight crowding, and 6.9% in dilated glands with infolding or
      outbranching. Ki-67 indices for dilated glands were most similar, therefore, to
      atrophic/inactive endometrium with no statistical significant difference in the
      percentage of these cells staining between these two groups. In contrast,
      statistically significant differences were seen in staining between cystic
      patterns of simple hyperplasia and proliferative endometrium, simple hyperplasia
      showing outbranching and/or slight crowding but no dilation, complex hyperplasia,
      and atypical hyperplasia. The findings in the current study suggest that
      nonatrophic cystic glands with an increase in the gland-to-stroma ratio in the
      endometrium should not be considered a hyperplastic process and in the absence of
      other findings such as excessive bleeding or coexistent noncystic simple
      hyperplasia, treatment with progestin therapy, a widely used practice, is
      unnecessary. As discussed, the findings also suggest that these cystic forms of
      simple hyperplasia are precursors of cystic atrophies. Confirmation of these
      results on a larger population by a different research team appears desirable.

PMID- 10907168
TI  - Elucidation of vascular structure of molar villi in complete hydatidiform mole by
      CD-34 antibody.
AB  - Vasculature was examined immunohistochemically in the villous stroma in 22 cases
      of complete hydatidiform mole (CHM). Only antibody CD-34 was able to detect the
      vasculature. Serial thin and thick sections and squashed preparations of molar
      villi were stained by CD-34, and sequential photographs of the vasculature were
      taken and projected on paper, and the vasculature was described and
      reconstructed. In the stroma of almost all molar villi examined, vessels were
      found, but their density and structure varied greatly in each molar villus even
      in the same CHM, and the vessels were irregular in diameter. In fully distended
      molar villi the vessels often became narrow, continuing like a broken line but
      eventually vanishing. Generally the density of the vessels was inversely
      proportional to the grade of the swelling of villi. The vessels sometimes passed
      through two adjacent molar vesicles. No significant differences in vasculature
      were found in molar villi at different gestational ages.

PMID- 10907169
TI  - Inhibin expression in normal and pre-eclamptic placental tissue.
AB  - Serum inhibin levels increase during normal pregnancy, but are significantly
      higher in patients with pre-eclampsia. The aim of this study was to demonstrate
      possible increased expression of inhibin within the placentas of women with pre
      eclampsia compared with non-pre-eclamptic controls. Cellular expression of
      inhibin alpha and beta A subunits was studied using immunohistochemistry on
      formalin-fixed, paraffin-embedded placental sections from cases of pre-eclampsia
      (n = 23) and gestational age-matched non-pre-eclamptic controls (n = 16).
      Immunohistochemistry was performed using monoclonal antibodies against inhibin
      alpha and beta A subunits by the indirect immunoperoxidase technique. Intensity
      of staining was graded by a semiquantitative scoring method. Differences in
      distribution and intensity of staining between control and pre-eclamptic
      placentas were analyzed using a nonparametric Mann-Whitney U test. Staining for
      both inhibin alpha and beta A was predominantly confined to the cytoplasm of
      syncytiotrophoblast, with weak expression within intermediate trophoblast. The
      intensity of staining for inhibin alpha was significantly greater in the
      syncytiotrophoblast of pre-eclamptic patients (mean staining intensity controls =
      0.97, disease = 1.87; p < 0.001). Inhibin beta A staining was generally stronger
      than for the alpha subunit, and was also significantly increased in pre-eclamptic
      patients compared with controls (mean controls = 1.72, disease 2.19; p < 0.05).
      This is the first evidence for increased placental inhibin presence in pre
      eclampsia, suggesting increased inhibin production within the placenta, a finding
      that could account for increased serum inhibin levels in pre-eclampsia.

PMID- 10907170
TI  - Comparison of the genetic alterations in two epithelial collision tumors of the
      uterine cervix. A report of two cases.
AB  - In a minority of cervical carcinomas, a distinct adenocarcinoma and squamous cell
      carcinoma component can be recognized. These tumors are considered collision
      tumors; the differential diagnosis is adenosquamous carcinoma. To investigate
      whether the squamous and adenocarcinoma component are of multiclonal or
      monoclonal origin, we used loss of heterozygosity (LOH) as a method to establish
      clonality. Each tumor component of two tumors with a distinct adenocarcinoma and
      squamous cell carcinoma component were microdissected and the presence of LOH was
      studied for nine chromosomes, i.e., 1, 2, 3, 6, 11, 15, 17, 18, and X, which are
      known to contain frequent LOH in cervical cancer. The tumor of patient AK13
      showed identical LOH in both the adenocarcinoma and squamous cell carcinoma
      tissue with various microsatellite markers on chromosomes 1, 2, 6, 18, and X. For
      markers on chromosomes 3 and 15, different LOH patterns were found in both
      components. The squamous epithelium showed LOH on chromosome 3, whereas the
      adenocarcinoma component had LOH on chromosome 15. For patient AK18 the LOH
      pattern on chromosomes 6p and 17 was the same in the adenocarcinoma and the
      squamous cell carcinoma component. The adenocarcinoma component showed additional
      LOH on chromosomes 6q and chromosome 11q. The tumor of patient AK18 showed common
      boundaries of LOH in both components on chromosome 17q, between markers D17S578
      and D17S250. In conclusion, the squamous cell carcinoma and adenocarcinoma
      components in both tumors most likely have one cell of origin because many
      genetic alterations are the same in each component. The presence of genetic
      changes uniquely associated with one of the tumors favors a diversion of
      developmental pathways.

PMID- 10907171
TI  - Papillary squamous cell carcinoma of the uterine cervix: report of three cases
      and a review of its classification.
AB  - Papillary squamous cell carcinoma (SCC) of the uterine cervix has been defined as
      a malignant squamous cell lesion characterized by a papillary architecture with
      fibrovascular cores and moderate to severe dysplasia devoid of frank
      keratinization and koilocytic change. Papillary SCC should be histopathologically
      delineated from other rare variants of SCC with papillary features including
      verrucous and condylomatous carcinoma and the recently recognized (squamo
      )transitional cell carcinoma of the uterine cervix. We report three cases of
      papillary SCC (FIGO stages IB, IV, and IVB) in postmenopausal women. Each tumor
      tested was positive for human papillomavirus (HPV) 16 and negative for HPV 6, 11
      and 18 by general primer mediated polymerase chain reaction and subsequent enzyme
      linked immunosorbent assay (PCR-ELISA). These findings 1) support the hypothesis
      that papillary SCCs (unlike verrucous carcinoma) are similar with regard to risk
      factors to (squamo-)transitional and condylomatous carcinoma; 2) suggest that HPV
      may play an etiologic role in at least some of these tumors; and 3) suggest that
      papillary SCC is the only subtype among squamous/(squamo-)transitional carcinomas
      that is associated with high-risk HPV infection in the absence of HPV-related
      histopathologic alterations.

PMID- 10907172
TI  - Non-Hodgkin's lymphoma involving the vulva.
AB  - Non-Hodgkin's lymphomas (NHL) involving the vulva are rare. We report the
      clinicopathologic and immunohistochemical findings of six cases of vulvar NHL.
      The age of the patients ranged from 43 to 71 years (mean 60 years), and 5
      presented with a vulvar mass. Two patients had neoplasms localized to the vulva,
      and two patients had a history of NHL that secondarily involved the vulva; in
      another patient the stage was unknown, and the sixth patient had stage IVA
      mycosis fungoides/Sezary syndrome involving the vulva. Each tumor was classified
      according to the revised European-American classification of lymphoid neoplasms:
      four were diffuse large B-cell lymphoma, one was peripheral T-cell lymphoma, and
      one was mycosis fungoides/Sezary syndrome. Two patients were treated with
      chemotherapy and radiotherapy, one patient received chemotherapy and
      phototherapy, one patient was treated with chemotherapy, and in two patients the
      treatment is unknown. Clinical follow-up, available for 4 cases, ranged from 7
      months to 5 years. One patient with low-stage NHL responded to therapy, but
      relapsed and died of disease 2 years later. Two patients with generalized NHL
      that secondarily involved the vulva died of disease 7 months and 5 years,
      respectively, after the diagnosis of vulvar involvement was established. The
      patient with mycosis fungoides/Sezary syndrome is alive with disease at 4 years.
      The three patients in this study who died and our review of the literature
      indicate that NHL involving the vulva is usually an aggressive disease.

PMID- 10907173
TI  - Screening for occult nodal metastasis in squamous cell carcinoma of the vulva.
AB  - Metastases to inguinofemoral lymph nodes in patients with carcinoma of the vulva
      alter the prognosis and treatment of this disease. Our goal was to determine if
      immunohistochemical staining could reveal occult metastatic nodal disease not
      detected with routine hematoxylin and eosin staining. We retrospectively examined
      a total of 110 lymph nodes from 10 patients who had undergone lymph node
      dissection and found to have all negative nodes. Paraffin embedded lymph nodes
      were immunostained with a monoclonal antibody directed against multiple low- and
      high-molecular weight cytokeratins. Micrometastases were not detected in any
      lymph nodes examined with immunohistochemistry. All positive and negative
      controls yielded satisfactory results. It is concluded that immunohistochemistry
      with cytokeratin antibodies does not provide greater sensitivity than routine
      hematoxylin and eosin staining for the detection of nodal metastases in vulvar
      carcinoma.

PMID- 10907174
TI  - Topoisomerase II alpha: prognostic predictor and cell cycle marker in surface
      epithelial neoplasms of the ovary and peritoneum.
AB  - Immunohistochemistry for Topoisomerase II alpha (TopoIIa), a nuclear protein
      important for the separation of chromosomes and deoxyribonucleic acid
      replication, provides insight into the molecular events in the cell cycle and the
      response to chemotherapeutic agents, which target TopoIIa. We test the hypothesis
      that the percentage of TopoIIa immunoreactive nuclei (TopoIIaI) aids in the
      treatment and prognostic evaluation of ovarian and primary peritoneal surface
      epithelial neoplasms (SENs) and correlates with established cell cycle control
      markers: p53, p21WAF1/CIP1 (p21), and Ki67. Paraffin sections from a
      retrospective surgical series of 108 SENs were immunostained with anti-TopoIIa,
      anti-p53, anti-p21, and anti-Ki67. The TopoIIaI, the Ki67 proliferation index
      (Ki67PI), and the immunoreactivity score for p53 and p21 (IMS: S1, S2, S3 < 10%,
      10 to 50%, > 50% of strong staining cells, respectively) were evaluated manually.
      TopoIIaI and Ki67PI ranged from 5 to 84% and 4 to 88% (mean/median: 31/30 and
      44/46%), respectively, and were correlated (coefficient 0.62, p < 10(-11)). IMS
      of 108 SENs was as follows: p53 50% + (2S1, 52S3) and p21 66% + (38S1, 12S2,
      21S3). The TopoIIaI associated directly with p53 (p < 10(-5) and inversely with
      p21 (p < 0.005) IMS. TopoIIaI correlated with SEN architectural/nuclear grade (p
      < 10(-5)/10(-7)), but not histologic type. Sixty-seven patients had disease at
      last follow-up, 55 were dead from disease at 2 to 67 months (mean/median 24/21),
      and 14 were alive with disease at 31 to 230 months (mean/median 73/59). Forty-one
      patients were disease free at 5 to 228 months (mean/median 75/54). TopoIIaI
      correlated with presence of disease (p < 0.01) and poor survival (p < 1 x 10(-9),
      even when only 93 invasive SEN cases are considered (p < 0.005). TopoIIaI
      correlates with poor prognosis and other cell cycle control markers. The patients
      in this retrospective series of SEN were treated primarily with platinum-based
      chemotherapy. These data may suggest further prospective studies in which
      patients with SENs exhibiting high TopoIIaI are treated with chemotherapy
      targeted against TopoIIa (e.g., etoposide). In this retrospective series, high
      SEN TopoIIaI predicted poor survival when treated with platinum-based
      chemotherapy, which does not target TopoIIa.

PMID- 10907175
TI  - Vasculitis of the female genital tract with clinicopathologic correlation: a
      study of 46 cases with follow-up.
AB  - Forty-six cases of vasculitis affecting the female genital tract are described;
      only 41 similar cases have been previously reported, either as case reports or
      small series. The age range of the patients was from 22 to 80 years, and most of
      them presented with abnormal bleeding or were being treated conditions unrelated
      to the vasculitis. There were 39 hysterectomy specimens (26 of which were derived
      from total abdominal hysterectomies) and seven specimens of the cervix only. The
      vasculitis was confined to the cervix in 30 of the 46 cases; in 24 of these, the
      entire uterus was available for examination. In 23 cases, only a single vessel
      was involved, and in the other 23 there was more extensive vessel involvement. In
      all cases, the involved vessels were arterioles and small arteries. In 42 cases,
      the arteritis was of the polyarteritis nodosa (PAN) type, and in four, of the
      giant cell type (GCA). Follow-up ranged from < 1 year to 23 (mean, 3) years.
      Systemic manifestations were previously diagnosed or subsequently developed in
      only four patients, three with PAN and one with GCA; in each of them, the genital
      tract vasculitis was found only in the cervix (in one of these, however, the
      specimen was a loop excision of the cervix and the rest of the uterus was not
      assessable). The three patients with PAN subsequently developed extragenital PAN
      (one case), PAN and rheumatoid arthritis (one case), or PAN and polymyalgia
      rheumatica (one case). The patient with GCA had previously documented temporal
      arteritis and temperomandibular arthritis. The findings in this series and in
      previously reported cases indicate that vasculitis of the female genital tract is
      only rarely associated with systemic vasculitis.

PMID- 10907176
TI  - Androgenic adult granulosa cell tumor in a 13-year-old prepubertal patient: a
      case report and review of the literature.
AB  - We report the clinicopathologic findings of an unusual case of adult granulosa
      cell tumor with androgenic manifestation in a 13-year-old prepubertal girl. The
      patient had never had a menstrual period and presented with a 1 year history of
      hirsutism. Physical examination was only remarkable for an increase in facial and
      abdominal hair, both with a male pattern of distribution. A pelvic ultrasound
      demonstrated a 6.0 cm right adnexal cyst. Plasma testosterone and 17
      hydroxyprogesterone levels were elevated. The patient initially was treated with
      monophasic oral contraceptive pills for 3 months and owing to lack of response,
      she underwent an exploratory laparotomy in which a left ovarian tumor, 7.0 cm in
      greatest dimension, and a 6.5 cm right paratubal cyst were found. A wedge biopsy
      of the left ovary and subsequent left oophorectomy with right salpingectomy were
      performed. No gross evidence of disease outside the ovary was noted. Microscopic
      examination of the left ovarian tumor revealed the typical features of an adult
      granulosa cell tumor. No tumor was seen outside the ovary. Six days after
      surgery, plasma testosterone and 17-hydroxyprogesterone levels were in the normal
      range. Nine months postoperatively, the patient shows no evidence of disease. To
      our knowledge, this represents the first case of a prepubertal patient with an
      adult granulosa cell tumor with androgenic manifestations reported in the English
      literature.

PMID- 10907177
TI  - Cotyledonoid leiomyoma of the uterus: report of a case.
AB  - A 46-year-old woman presented with a pelvic mass. At the time of operation a
      large, exophytic, multinodular tumor extended into the peritoneal cavity and
      right broad ligament from a pedunculated attachment to the uterus in the region
      of the right cornu. On external examination the lesion had the appearance of
      cotyledonoid dissecting leiomyoma. On microscopic examination bulbous processes
      were composed of benign smooth muscle arranged in interlacing fascicles or
      swirls; there was focal hydropic degeneration. Significant nuclear atypia,
      mitotic activity, and coagulative tumor necrosis were not encountered. No
      intravascular involvement was present. There was no demonstrable parent leiomyoma
      or intramural dissecting component, and thus the case differed from previously
      reported cases of both cotyledonoid dissecting leiomyoma and intramural
      dissecting leiomyoma. This tumor represents another variation in the group of
      benign uterine smooth muscle tumors with unusual growth patterns.

PMID- 10907178
TI  - Benign, borderline, and malignant endometrioid neoplasia arising in endometriosis
      in association with tamoxifen therapy.
AB  - Tamoxifen therapy may result in a variety of endometrial proliferative lesions,
      including adenocarcinoma, and as recently suggested, proliferative changes within
      endometriosis. This report describes an endometrioid adenocarcinoma arising in
      ovarian endometriosis in a patient taking tamoxifen. There were also foci of
      benign and borderline endometrioid adenofibroma in the same ovary and a
      synchronous endometrioid endometrial adenocarcinoma in the uterus. The spectrum
      of benign, borderline, and malignant endometrioid neoplasia arising within
      endometriosis suggests that tamoxifen, as a result of its estrogenic effects, may
      cause proliferative and, in rare instances, malignant changes in endometriosis.

PMID- 10907179
TI  - Adenomyofibroma of the endometrium with skeletal muscle differentiation.
AB  - A case of adenomyofibroma with skeletal muscle differentiation is described. A 55
      year-old asymptomatic woman had atypical glandular cells of undetermined
      significance on a routine Papanicolaou smear. The endometrial biopsy revealed
      fragments composed of benign endometrial glands and myofibromatous stroma with
      foci of skeletal muscle differentiation. The stroma exhibited focal mild
      cytologic atypia and hypercellularity without periglandular cuffing or mitoses.
      Electron microscopy and immunohistochemical staining for myoglobin confirmed the
      skeletal muscle differentiation. A diagnosis of low-grade adenosarcoma with
      heterologous differentiation was made in the biopsy specimen based on the
      atypical stroma, the skeletal muscle differentiation, and previous observations
      that adenosarcomas may contain bland areas indistinguishable from an
      adenofibroma. The patient underwent hysterectomy, bilateral salpingo
      oophorectomy, and pelvic lymphadenectomy. The hysterectomy specimen revealed
      small foci of residual tumor. In light of these findings the diagnosis was
      revised to adenomyofibroma with skeletal muscle differentiation. Uterine
      adenomyofibroma with skeletal muscle differentiation should be distinguished from
      a low-grade adenosarcoma in an endometrial biopsy.

PMID- 10907180
TI  - History of gynecological pathology. VIII. John Hammond Teacher.

PMID- 10907181
TI  - Mitotic activity in spindle cell neoplasms treated with gonadotropin-releasing
      hormone agonists (leuprolide acetate).

PMID- 10907182
TI  - [Geriatrics in science and research].

PMID- 10907183
TI  - [Cardiovascular function and functional disorders in extreme old age].

PMID- 10907184
TI  - [Endocrine and metabolic functional disorders in extreme old age].

PMID- 10907185
TI  - [Neuropathology and biological markers of degenerative dementias].

PMID- 10907186
TI  - [Chief psychiatric problems in old age].

PMID- 10907187
TI  - [Age factors in cancer therapy].

PMID- 10907188
TI  - [Intensive care of extremely old patients in internal medicine].

PMID- 10907190
TI  - [Postgraduate education in geriatrics for physicians].

PMID- 10907189
TI  - [Care for patients in extreme old age by the internist in clinical practice].

PMID- 10907191
TI  - [Chronic pancreatitis].

PMID- 10907192
TI  - [Manifestation of adrenal insufficiency after administration of levothyroxine in
      a patient with polyglangular autoimmune syndrome type II (Schmidt-syndrome)].

PMID- 10907193
TI  - [47-year old patient with painful overheating of the dorsal surface of the foot].

PMID- 10907194
TI  - [Reflux disease and Helicobacter pylori].

PMID- 10907195
TI  - [Therapy of deep vein thrombophlebitis].

PMID- 10907196
TI  - [Quality management requires continuous education. Part 2: Infections-
      noninfectious dermatoses--peripheral venous diseases].

PMID- 10907197
TI  - Imprinting.

PMID- 10907198
TI  - Movement disorders is a branch of neurology that deals specifically with brain
      disorders affecting movement.

PMID- 10907199
TI  - Quality of life in clinical nursing practice.

PMID- 10907200
TI  - Pain in multiple sclerosis: an overview of its nature and management.
AB  - Pain is experienced by approximately two-thirds of all people with multiple
      sclerosis (MS) at some time during the course of their disease. Pain in MS occurs
      as a consequence of both the disease and the disability that it produces. Pain in
      MS is receiving more attention as clinical trials in the past decade have focused
      not solely on the immune system modulators of disease but also on symptomatic
      management as well. Nurses with their keen communication and assessment skills
      and their unique advocacy role are particularly equipped to effect pain
      management for people with multiple sclerosis.

PMID- 10907201
TI  - An epilepsy care package: the nurse specialist's role.
AB  - Deficiencies in existing primary care for people with epilepsy are well
      recognized in the United Kingdom and include a lack of structure and an inability
      to meet the patients' needs for information and support to cope with their
      epilepsy. The introduction of clinics set up by nurse specialists within family
      practice in a few United Kingdom cities has met with a high degree of
      acceptability and satisfaction from patients. A package of care was developed to
      support epilepsy management in the community in the United Kingdom. It includes
      provision of advice and information, counseling, and interdisciplinary liaison.
      Nurse specialists with a sound training in epilepsy can adopt a proactive role
      and effectively deliver this package.

PMID- 10907202
TI  - Effective nursing interventions for the management of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes
      severe deterioration of functional and cognitive abilities. As the leading cause
      of dementia in adults, it affects one in every 10 people who are more than 65
      years of age. There is a vital need for neuroscience nurses with knowledge of AD
      to provide high-quality care for the growing number of patients. The use of
      effective nursing interventions for the management of AD can help nurses promote
      independence and quality of life for AD patients. Nursing care must include
      interventions that focus on maintaining AD patients' functional and cognitive
      abilities as well as on preventing further disability and decline. Nurses can
      implement these measures in acute, long-term, and home healthcare settings.

PMID- 10907203
TI  - Identifying patients "at risk" for alcohol withdrawal syndrome and a treatment
      protocol.
AB  - Alcohol abuse and alcohol dependence are common problems. It is estimated that
      more than 10 million Americans have problems with alcohol dependence that
      adversely affect their lives and the lives of their families. Many of these
      patients, if hospitalized, have the potential to experience symptoms of alcohol
      withdrawal. Major alcohol withdrawal symptoms may include seizures and the
      development of delirium tremens. Obtaining an alcohol consumption history is a
      critical component to identifying patients at risk and determining the
      appropriate treatment plan for potential alcohol withdrawal. A protocol was
      established for identifying and treating patients at risk for alcohol withdrawal.
      The initiation of the treatment protocol is history- and symptom-based; treatment
      is symptom-triggered on the basis of frequent objective assessments. The purpose
      of the protocol is to prevent and control withdrawal symptoms without heavily
      sedating or hindering a patients' neurological assessment.

PMID- 10907204
TI  - Skin hemodynamics during change from supine to lateral position.
AB  - The purpose of this study was to identify the skin hemodynamics during the
      position change from supine to lateral in patients with neurodegenerative
      diseases. The participants were 19 patients with neurodegenerative diseases and
      12 healthy volunteers. The alteration in the total concentration of oxyhemoglobin
      and deoxyhemoglobin, indicative of change in blood volume, was measured in the
      skin of the left flank by using a portable noninvasive tissue oxygen monitor by
      near-infrared spectroscopy. The positions were changed from the left and right
      lateral with a return to the supine between each procedure. In healthy
      volunteers, total hemoglobin concentration (skin blood volume) increased when the
      position changed from supine to left lateral and decreased when changed from
      supine to right lateral. The decreased skin blood volume gradually recovered
      after a change from the supine to the right lateral position in healthy
      volunteers. However, it did not recover in three sporadic olivopontocerebellar
      atrophy (OPCA) patients with marked autonomic dysfunction and one Parkinsonian
      patient with severe orthostatic hypotension. Our study identified that the
      intracutaneous blood was changing dynamically during the position change from
      supine to lateral and was regulated by autonomic nerve function.

PMID- 10907205
TI  - The biobehavioral correlates of post-traumatic brain injury depression.
AB  - Traumatic brain injury (TBI), typically resulting from vehicle accidents or acts
      of violence, is a major public health concern. Survivors often face lifelong
      impairments affecting functional status, cognition, and mood. Depression, the
      most common mood disorder affecting TBI survivors, most likely is underdiagnosed
      and presents differently than primary depression or depression after other brain
      insults. Unfortunately, few studies have been reported that advance theoretical
      perspectives on post-TBI depression. Currently, there is some evidence that
      neurochemical and anatomical changes contribute to post-TBI depression.
      Interpersonal factors, such as sense of belonging and social support, may
      contribute to the incidence of post-TBI depression. Because of limited
      theoretical viewpoints, advances have not been made in cost-effective and
      efficient interventions for this mood disorder, which prolongs rehabilitation and
      contributes to family suffering.

PMID- 10907207
TI  - Compliance and noncompliance in neuroscience.
AB  - Among the responses to this month's question, the most common strategy for
      motivating compliance is providing information. This finding is also supported
      with the example from Australia, where stoke sufferers are highly compliant with
      any intervention aimed at prevention of future strokes. In this case, the high
      level of compliance and (probably) motivation can be explained by the fact that
      stroke is potentially fatal and highly disabling. Other important issues also
      were identified in the responses: (a) patients' trust and belief in healthcare
      professionals in terms of providing information and motivation, and (b) a lack of
      motivation in some patients who simply do not want to comply and prefer a certain
      level of seizure activity or other impairments and disabilities over the
      potential side effects of the treatment. This raises another question that goes
      beyond the concept of compliance and noncompliance: How does the system comply to
      the patient? I will leave this topic open, and I welcome comments for a future
      round of discussion here at Global Views.

PMID- 10907206
TI  - The neurobiology of antidepressants.
AB  - Raising neurotransmitter levels is only one means by which antidepressants act.
      The activity of modern drugs appears to readjust the balance between serotonin
      and noradrenaline by more fundamental means. Likely mechanisms include correction
      of the diminished sensitivity and numbers of specific serotonin and noradrenaline
      receptors found in depression. Also responsible may be changes in the normal
      pattern of movements of these transmitters across the synaptic membranes within
      the diffuse modulatory systems. It is possible that by increasing the serotonin
      levels these drugs may increase neurogenesis, suggesting that neuronal losses may
      be a fundamental cause of the symptoms.

PMID- 10907208
TI  - Obstetric and gynecologic milestones.

PMID- 10907209
TI  - Sexual problems as a matter of course.
AB  - The two most fundamental aspects of sexual relationships, passion and intimacy,
      are complex concepts, with at least partly paradoxical contents. Intimacy, for
      example, stands for unity and security, but also for shifting boundaries and
      exposure. Passion in its turn, stands for enthusiasm and energy, but also for
      surrender and dependency. It is this 'two sides of the coin' phenomenon that
      makes sexual relationships as interesting as they are dangerous. In terms of
      development, a relationship often starts with 'setting each other on fire' and
      ends with 'sexual burn-out'. In this paper, an analysis is made of the way
      patients, but also health care providers such as gynecologists and sexologists,
      cope with these unavoidable phenomena in sexual relationships.

PMID- 10907210
TI  - Premenstrual symptoms are relieved by massage therapy.
AB  - Twenty-four women meeting Diagnostic and Statistical Manual of Mental Disorders
      (4th edn; DSM-IV) criteria for premenstrual dysphoric disorder (PDD) were
      randomly assigned to a massage therapy or a relaxation therapy group. The massage
      group showed decreases in anxiety, depressed mood and pain immediately after the
      first and last massage sessions. The longer term (5 week) effects of massage
      therapy included a reduction in pain and water retention and overall menstrual
      distress. However, no long-term changes were observed in the massaged group's
      activity level or mood. Future studies might examine the effects of a longer
      massage therapy program on these symptoms. Overall, the findings from this study
      suggest that massage therapy may be an effective adjunct therapy for treating
      severe premenstrual symptoms.

PMID- 10907212
TI  - Functioning in daily living and psychological well-being of female cancer
      patients.
AB  - The objective of this prospective study was to compare outcomes concerning
      psychological and physical functioning of patients with various gynecological
      malignancies. A sample of 119 newly diagnosed cancer patients completed two
      questionnaires evaluating psychological well-being and functioning in daily
      living. Outcome measures were obtained at three time points: before surgery, 3
      months after surgery, and 1 year after surgery. The results showed that the
      psychological well-being improved significantly from the first to the third time
      point for the sample as a whole. After surgery, patients with ovarian and
      cervical cancer showed slightly lower scores than patients with endometrial
      cancer. The level of functioning in daily living declined 3 months after surgery
      for all except endometrial cancer patients, but increased significantly at the 1
      year follow-up. At all three time points the mean differences for psychological
      well-being and functioning in daily living were not statistically significant
      among subgroups. Physical and psychological well-being of the patients treated
      for gynecological malignancies is affected independently of age, cancer site and
      stage of disease. However, throughout the observational period the psychological
      well-being scores were lower than those of patients with other chronic illnesses
      or healthy subjects. Therefore, we conclude that psychological interventions for
      patients facing gynecological cancer treatment should be provided as an integral
      component of cancer management.

PMID- 10907211
TI  - Relationships of premenstrual dysphoric disorder to major depression and anxiety
      disorders: a re-examination.
AB  - Clarifying the relationships of premenstrual dysphoric disorder (PMDD) to
      depressive and anxiety disorders may contribute to the understanding of risk
      factors and etiologies associated with the disorders. A current belief is that
      women with PMDD have a higher percentage of past psychiatric disorders than women
      without the disorder, an assumption that may be premature. This review carefully
      examines existing literature on the nature of the relationships between PMDD and
      major depression and anxiety disorders. A re-evaluation of the literature and the
      resulting implications for risk factors and etiology, as well as for obstetric
      and gynecological practice, are provided.

PMID- 10907213
TI  - Changes in personality pattern during the first pregnancy and lactation.
AB  - In order to study personality changes in first pregnancy and lactation, two
      groups of women (n = 161, mean age 26.8 years) completed the self-report
      inventory Karolinska Scales of Personality and a scale for emotional dependency
      during pregnancy and 3 or 6 months after delivery. The results were within normal
      limits when compared with the normative values. Analysis of variance showed that
      the subscales Muscular Tension, Somatic Anxiety, and Monotony Avoidance
      diminished significantly from pregnancy and to the test periods after delivery
      (all p values < 0.01). Impulsiveness showed the same trend (p = 0.1). The women
      who had breastfed for at least 8 weeks (91%) differed significantly from those
      who had not. They had lower scores on the Somatic Anxiety (p = 0.006), Muscular
      Tension (p = 0.003), Monotony Avoidance (p = 0.039), Suspicion (p = 0.03), Social
      Desirability (p = 0.045) and the Impulsiveness scale (p = 0.078) and higher
      scores on the Socialization scale (p = 0.001). Thus, we conclude that most
      personality traits are stable during first pregnancy and lactation, but some
      significant changes occur toward a lifestyle interpreted as more relaxed and
      tolerant to monotony.

PMID- 10907215
TI  - Physicians' role and gender differences in the management of parents of a
      stillborn child: a nationwide study.
AB  - During spring 1997 all gynecologists working at gynecology departments in Sweden
      were sent a questionnaire regarding their role in, and attitudes to, the
      management of the parents of a stillborn child. Of 871 gynecologists approached,
      761 answered the questionnaire (87%). The majority considered that the parents
      should hold the child (94%), that the child should be given a name (80%) and that
      the child should be photographed (92%). A smaller proportion considered that
      labor should be started within 24 h (40%) and that siblings should see the child
      (55%). A minority experienced guilt at what had happened (12%) and one-third were
      anxious about possible disciplinary measures (30%). The majority of the
      gynecologists stated that the need for guidance was urgent (90%) but that only a
      minority had received this (40%). Regarding gender differences, it emerged that
      the female gynecologists did not consider there was an age limit for siblings to
      see the child (p = 0.003), were less inclined to prescribe tranquilizers (p =
      0.001) or to prolong the parents' sick-listing (p = 0.020). These differences
      remained after regression analysis was performed using background variables as
      covariates. In summary, this study demonstrates a great need for guidance; but
      that only a minority of the gynecologists get this. The lack of guidance/training
      may in the future increase the risk of this professional group becoming 'burnt
      out'.

PMID- 10907216
TI  - Delusional pregnancy in a patient with primary sterility.
AB  - The case of a patient suffering from primary sterility who developed a well
      systemized delusion of pregnancy is described. The patient did not have a history
      of psychiatric disorder or organic cerebral pathology. No history of epilepsy was
      detected in this patient contrary to the reports in the literature, and these
      facts have pathogenic relevance in delusional pregnancy. The importance of
      psychological factors in the development of a delusion of pregnancy is discussed.

PMID- 10907214
TI  - Pregnancy and diabetes--a hermeneutic phenomenological study of women's
      experiences.
AB  - The aim of this article is to describe women's experiences of being pregnant and
      having insulin-dependent diabetes mellitus (IDDM), particularly regarding what
      the crucial elements of the experience are during pregnancy. A qualitative method
      with a hermeneutic phenomenological approach was used. The subjects were 14
      pregnant women with IDDM, of whom eight were primiparous and six multiparous.
      They were interviewed during pregnancy concerning their experience of 'being
      controlled by blood glucose levels for the child's sake'. The child makes
      demands, with consequences which are divided into two main themes:
      objectification, including loss of control and an awareness of having an unwell
      'risky body'; and exaggerated responsibility, including constant worry, constant
      pressure and constant self-blame. The results present a challenge to every
      midwife, physician or other health professional involved in the care of pregnant
      women with diabetes. They have an important role in mediating understanding of
      how risks to such women during pregnancy and childbirth can be minimized by
      normalizing the blood glucose level. At the same time, they should point out the
      fact that most women with IDDM today have healthy babies. This could reduce
      negative feelings. The women should also be supported and encouraged in the
      normal transition to motherhood.

PMID- 10907217
TI  - Glycosylated haemoglobin assay of canine blood samples.
AB  - A method for assaying canine glycosylated haemoglobin was evaluated. The method
      is a turbidimetric inhibition immunoassay and the final reaction is
      bichromatically measured using a multichannel automatic analyser. Within-run
      coefficients of variation (2.07 to 4.46 per cent) were permissible, but between
      run coefficients of variation (2.10 to 8.25 per cent) were slightly more
      elevated. The detection limit of this assay is 0.052 per cent. A sample dilution
      of 10 microliters of sample and 500 microliters of haemolysing reagent is
      recommended for routine analysis of canine blood samples. A normal reference
      interval of 1.39 +/- 0.70 per cent was obtained from the glycosylated haemoglobin
      analysis in 82 healthy dogs and no statistically significant differences in
      relation to age or gender were observed. Some changes in glycosylated haemoglobin
      concentrations were noted throughout the ovarian cycle, although differences
      between dogs were evident. Since this assay specifically measures the
      glycosylated haemoglobin content in canine blood samples, it could be very useful
      for monitoring diabetic dogs.

PMID- 10907219
TI  - Clinical evaluation of a valveless non-absorber breathing system in spontaneously
      breathing canine patients.
AB  - A valveless non-absorber breathing system novel to veterinary anaesthesia is
      described. The performance of this system was evaluated in 35 anaesthetised
      spontaneously breathing dogs weighing between 2.1 and 56 kg. Fresh gas flows were
      reduced incrementally until rebreathing (defined as an increase in end-inspired
      carbon dioxide tension above 0.2 per cent) started to occur, as measured by
      capnography. A significant relationship (P < 0.0001) between critical fresh gas
      flow and bodyweight was determined, and a mean critical fresh gas flow rate of
      145 +/- 21 ml/kg/minute was derived for 15 dogs weighing 10 kg or less (mean 6.7
      +/- 2.6 kg) and one of 98 +/- 16 ml/kg/minute for the remaining 20 dogs weighing
      11 kg or greater (mean 30.2 +/- 13.9 kg). The fresh gas requirements for each
      group were found to differ significantly (P < 0.0001), although the correlation
      between critical fresh gas flow and bodyweight was not significant (P = 0.054) in
      the dogs weighing 10 kg or less. It is suggested that the system may prove an
      economical and useful addition to the breathing systems currently used in canine
      anaesthesia.

PMID- 10907218
TI  - Cranial cruciate stability in the rottweiler and racing greyhound: an in vitro
      study.
AB  - An in vitro biomechanical study of cadaver stifles from rottweilers and racing
      greyhounds was undertaken to evaluate the contribution of the cranial cruciate
      ligament to stifle joint stability. This was performed at differing stifle joint
      angles, first with the joint capsules and ligaments intact and then with all
      structures removed except for the cranial cruciate ligament. Craniocaudal laxity
      increased in both breeds as stifle flexion increased. The rottweiler stifle
      showed greater craniocaudal joint laxity than the racing greyhound at all joint
      angles between 150 degrees and 110 degrees, but the actual increases in joint
      laxity between these joint angles were similar for both breeds. Tibial rotation
      during craniocaudal loading of the stifle increased craniocaudal laxity in both
      breeds during joint flexion. The relative contribution of the cranial cruciate
      ligament to cranial stability of the stifle joint increased as the joint flexed
      and was similar in both breeds.

PMID- 10907220
TI  - Iatrogenic pupillary dilation resembling Pourfour du Petit syndrome in three
      cats.
AB  - A condition resembling Pourfour du Petit syndrome, where there are signs of
      sympathetic hyperactivity to the eye, is described in three cats as a result of
      mild trauma to the middle ear cavity.

PMID- 10907221
TI  - Talar neck fractures in five cats.
AB  - Five cats with fracture of the talar neck were treated using external skeletal
      fixation (ESF). In four of the cases, ESF was the only fixation technique used
      and this was applied in a closed manner coupled with traction. In the remaining
      cat, ESF was used in combination with a lag screw. All the fractures eventually
      healed, demonstrating that ESF provided a simple and effective method of
      treatment for these cases.

PMID- 10907222
TI  - Clinical application of prong-type tissue anchors in small animal surgery.
AB  - Prong-type tissue anchors were used in six dogs and one cat in a variety of
      orthopaedic procedures in order to aid repair and replacement of tendons and
      ligaments. All animals returned to normal function with minimal problems.

PMID- 10907223
TI  - Clinical, radiological and pathological features of 12 Irish setters with canine
      leucocyte adhesion deficiency.
AB  - The clinical, radiological and pathological findings in 12 dogs with canine
      leucocyte adhesion deficiency (CLAD) from six litters are described. All the dogs
      were younger than 15 weeks at admission, all had been febrile and 11 had been
      treated with antibiotics. Seven had been treated for omphalophlebitis. At
      admission, all had gingivitis, lymph node enlargement and profound neutrophilia.
      Ten dogs were radiographed and showed various skeletal lesions compatible with
      metaphyseal osteopathy, craniomandibular osteopathy and osteomyelitis. Four dogs
      had clinical signs of respiratory distress and seven exhibited a mild
      interstitial pneumonia at necropsy. Six dogs had skin wounds, with strikingly few
      neutrophils seen on stained sections. All dogs were euthanased before six months
      of age due to severe and incurable infections. The clinical signs, radiological
      features and haematology were strongly suggestive of CLAD. The diagnosis was
      confirmed by granulocyte function tests and flow cytometry, which revealed
      impaired adhesion, impaired C3b-mediated phagocytosis and absence of adhesion
      proteins CD11b/CD18.

PMID- 10907224
TI  - Tears of the palmar superficial fascia in five racing greyhounds and a Labrador
      retriever.
AB  - Tears of the palmar superficial fascia over the palmar extremity of the accessory
      carpal bone were identified as the cause of lameness in five racing greyhounds
      and as a coincidental finding in a Labrador retriever with an avulsion of the
      insertion of the flexor carpi ulnaris tendon. The lameness in the greyhounds was
      mild and transient, although racing performance was affected. The Labrador
      retriever was severely lame. In all cases there was a marked soft tissue swelling
      and a palpable defect in the superficial fascia. One case was managed
      conservatively and surgical repair was performed in the remaining five cases. The
      greyhounds returned to successful racing and the Labrador retriever made a
      complete recovery.

PMID- 10907225
TI  - Feline upper respiratory tract disease.

PMID- 10907226
TI  - Microchip adverse reactions.

PMID- 10907227
TI  - Magnesium transport from aqueous solutions across Caco-2 cells--an experimental
      model for intestinal bioavailability studies. Physiological considerations and
      recommendations.
AB  - The Caco-2 cell model is gaining more and more importance as an in vitro method
      to study intestinal nutrient bioavailability from foods. In a previous article we
      presented evidence that fractional Mg2+ transport from different aqueous
      solutions containing differing amounts of magnesium varies considerably in some
      cases. In the present article we discuss the role of electrolytes, such as
      calcium and the anions HCO3-, SO4(2-) and Cl-, in modulating magnesium
      absorption. Another purpose of this manuscript is to give recommendations, based
      mainly on physiological knowledge, which can be helpful when planning and
      conducting intestinal bioavailability studies using either the Caco-2 culture
      system or other in vitro models in order to achieve nearly similar conditions as
      in vivo.

PMID- 10907228
TI  - Normal values for serum, ultrafilterable and intraerythrocytic magnesium in
      children.
AB  - Serum magnesium (MgS), levels were determined in 137 children age range 2 months
      to 16 years. Ultrafilterable magnesium (MgU) and intraerythrocytic magnesium
      (MgI) concentrations were determined in 37 of these children. MgS was 0.83 +/-
      0.1 mmol/L (range 0.66-1.36 mmol/L), with no differences between sexes. Children
      under 2 years had higher MgS levels (0.92 +/- 0.13 mmol/L) than children over 2
      years (0.81 +/- 0.08 mmol/L; p < .001). Mean MgU was 0.60 +/- 0.07 mmol/L (range
      0.50-0.87 mmol/L), with no differences between sexes. Mean MgI in children was
      2.58 +/- 0.33 mmol/L (range 2.06-3.6 mmol/L), with no differences between sexes.
      MgS correlated with MgU, age, theoretical growth rate, and serum calcium,
      phosphorus and alkaline phosphatase; MgU correlated with MgI, age, theoretical
      growth rate, and serum phosphorus. MgS concentration was higher in children under
      2 years than in children over 2 years. In healthy children, MgS concentration
      correlated with MgU, and MgU correlated with MgI, but MgS and MgI showed no
      correlation.

PMID- 10907229
TI  - Effect of intravenous magnesium on ventricular tachyarrhythmias associated with
      acute myocardial infarction.
AB  - Ventricular ectopy and left ventricular dysfunction are important predictive
      factors for an unfavourable outcome following an acute myocardial infarction
      (MI). Tachyarrhythmias are a major cause of death subsequent to MI. Magnesium was
      postulated to have an antiarrhythmic effect after MI. Therefore we have
      investigated the influence of intravenous and oral magnesium (Mg) therapy on
      ventricular tachyarrhythmias. 67 patients with myocardial infarction (MI)
      diagnosed according to the WHO criteria of anamnesis, infarct-specific
      electrocardiogram (ECG), and enzymatic status were included in a prospective
      study. 23 patients (group 1) received 2 g Mg per day (= 82 mmol Mg/24 h)
      intravenously for the first 3 days followed by oral magnesium adipate
      administration of 3 x 2 coated tablets of magnesium 50 Apogepha (= 300 mg Mg/24 h
      or 12.34 mmol Mg/24 h, respectively) for the full duration of the study. 26
      patients (group 2) received only i.v. magnesium for the first 3 days after
      admission (2 g Mg/24 h). The results of this treatment were compared to those of
      a control group of 18 MI patients without magnesium administration. All groups
      were identical with regard to other forms of treatment. The magnesium levels in
      serum and erythrocytes of all patients were measured at the following time
      points: days 0 (admission time), 1, 2, the day of discharge (about day 20) and
      after 12 weeks. The tachyarrhythmias were monitored by 24-h-continuous
      electrocardiography on days 0, 1 and on the day before discharge (about day 20).
      The serum magnesium levels rose significantly during i.v. Mg-administration (1
      and 2 day) but decreased in group 2 subsequently until the time of discharge from
      hospital. In contrast group 1 patients receiving oral as well as intravenous
      magnesium did not show this drop. The uptake of magnesium into the erythrocytes
      was less obvious. The erythrocyte magnesium concentration of the control group
      remained significantly low in serum and red blood cells. Significantly less
      ventricular premature beats and runs (< 5 ventricular premature beats and > 5
      ventricular premature beats) compared to admission day were observed in both
      treated groups. These data suggest that the frequency of ventricular
      tachyarrhythmias is reduced by administration of intravenous magnesium and
      support an early high dose administration of intravenous magnesium in the wake of
      myocardial infarction.

PMID- 10907230
TI  - Mechanisms of Mg2+ influx, efflux and intracellular 'muffling' in leech neurones
      and glial cells.
AB  - Mg2+ is known to influence conductance and gating properties of a multitude of
      ion channels and is thus able to modulate synaptic transmission. Therefore, a
      tight regulation of the intracellular free Mg2+ concentration ([Mg2+]i) in
      neurones and glial cells is crucial for maintaining the functions of central
      nervous systems. [Mg2+]i is regulated through the balance of Mg2+ influx and Mg2+
      efflux, together with heavy damping of [Mg2+]i changes through intracellular
      buffering and sequestration. To investigate the mechanisms involved in [Mg2+]i
      regulation, neurones and glial cells from the central nervous system of the leech
      Hirudo medicinalis proved to be an ideal model system. The present article
      summarizes the evidence for a Mg2+ influx pathway which is distinct from that for
      Ca2+, for a dual regulation of Mg2+ efflux (a 1 Na+/1 Mg2+ antiport and a Na(+)
      independent Mg2+ efflux mechanism), for pH-dependent Mg2+ buffering through ATP
      and other intracellular Mg2+ binding components and for the involvement of
      mitochondria in intracellular Mg2+ sequestration.

PMID- 10907231
TI  - Can magnesium act as a second messenger? Current data on translocation induced by
      various biologically active substances.
AB  - Free intracellular Mg2+([Mg2+]i) can potentially integrate the signals from
      hormones, cellular metabolism and organismal ion homeostasis and affect the
      activities of ion channel and other effectors. Interest in [Mg2+]i has been
      heightened by recent reports that small changes in [Mg2+]i in the physiological
      range can significantly modulate important cellular functions. In addition, a
      variety of new evidence shows that [Mg2+]i instantaneously changes following
      stimulation with various biologically active substances. These observations
      suggest that [Mg2+]i may act as a second messenger.

PMID- 10907232
TI  - Interactive effects of food additives on functional and nutritional properties.

PMID- 10907233
TI  - Protein-lipid interactions in edible films and coatings.
AB  - Proteins and lipids are capable of interacting in a many different ways to form
      effective edible films and coatings. Combinations of proteins and lipids function
      in a variety of colloidal systems such as emulsions and microemulsions. Edible
      films and coatings can be formed from both of these starting systems. In
      addition, laminant films can be developed by overlaying proteins and lipids.
      Covalent bonding of lipids to proteins through lipophilization offers unique
      opportunities for film formation with improved properties. This manuscript
      reviews recent research on film formation and properties of each of these film
      types and discusses their relative advantages and disadvantages. Applications of
      protein-lipid films to food systems are examined. Promising areas for future
      research are identified.

PMID- 10907234
TI  - Fruit-alginate interactions in novel restructured products.
AB  - Novel, healthy, value-added restructured fruit products meet consumer demand for
      an improved diet containing increasing amounts of fruit. As primary ingredients,
      fruit purees promise to provide new outlets for visually imperfect fruit or fruit
      that is too small for the fresh or canned markets. Generally these new product
      forms require a texturizing agent such as alginate to control the functional
      properties of the final restructured fruit products. Traditional alginate and
      pectin gel systems are reviewed in this manuscript as are mixed gel systems.
      Recent research results describing the production and properties of novel
      restructured products containing high-guluronic alginate and peach puree without
      any additional calcium or sugar source are reviewed. Effects of fruit/alginate
      interactions on gel formation conditions and texture profile results are
      evaluated.

PMID- 10907235
TI  - Antioxidants in food and food antioxidants.
AB  - Antioxidants may be present in foods as endogenous factors or may be added to
      preserve their lipid components from quality deterioration. Synthetic
      antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene
      (BHT), propyl gallate (PG) and tert-butylhydroquinone (TBHQ) are commonly used in
      food formulations. However, due to safety concerns, interest in natural
      antioxidants has intensified. To address the demand by consumers, mixed
      tocopherols, herbal extracts such as those of rosemary and sage, as well as tea
      extracts have been commercialized for food and nutraceutical applications. An
      overview of the topic is provided in this article.

PMID- 10907236
TI  - Effect of beta-cyclodextrin on pasting properties of wheat starch.
AB  - Changes of viscosity characteristics of genetically diverse hexaploid wheat
      starches during pasting in water, 1% NaCl solution, or at pH 4 or pH 10 were
      studied using a Rapid Visco-Analyzer. Peak viscosity (PV), hot paste viscosity
      (HPV) and cool paste viscosity (CPV) of all the wheat starches was little
      affected in pH 4 and pH 10 treatments. In 1% NaCl, all starches showed
      substantial increases in all three parameters relative to pasting in water. The
      use of 1% beta-cyclodextrin (beta-CD) (cycloheptaamylose) solution increased PV
      of high-swelling starches, but generally slightly decreased that of low swelling
      starches in all treatment conditions. HPV was always reduced by addition of 1%
      beta-CD, but CPV was increased in most treatments for Anza and Yecora Rojo (low
      swelling), but decreased for Klasic (high swelling). Bacterial alpha-amylase was
      added to starch or flour. The effect of beta-CD was shown to be independent of
      alpha-amylase inhibition in wheat starch, but beta-CD strongly inhibited alpha
      amylase in wheat flour.

PMID- 10907237
TI  - Cantaloupe melon peroxidase: characterization and effects of additives on
      activity.
AB  - Peroxidase in cantaloupe melon (Cucumis melo L. var. reticulatus Naud.), a fruit
      commonly fresh cut processed, was characterized to determine reaction pathway,
      optimal conditions for activity and effect of some additives on enzymatic action.
      Mn2+, CaCl2, NaNO2 and kinetin had partial inhibitory effects on enzyme activity.
      Activity was effectively inhibited by compounds capable of chelating peroxidase
      heme iron such as diethyldithiocarbamate and tiron, but unaffected by EDTA. Free
      radical scavenger, superoxide dismutase, also had no effect on reaction velocity.
      Enzymatic action was consistent with that of ascorbate peroxidase based on the
      relatively higher affinity for ascorbate over guaiacol. Optimum activity
      temperature was 50-55 degrees C. The enzyme was stable at temperatures below 40
      degrees C and at 50 degrees C for up to 10 min. Over 90% of total activity was
      lost at 80 degrees C within 5 min. Broad pH optima, 5.5-7.5 at 50 degrees C and 6
      7 at 30 degrees C, were obtained. Peroxidase activity in cantaloupe was higher
      than those in strawberry (Fragaria ananassa Duch.) and lettuce (Lactuca sativa
      L.), suggesting a relatively high oxidative stress in fresh cut cantaloupe. The
      potential use of ascorbate as an additive in fresh cut cantaloupe melon was
      demonstrated by its ability to preserve color in minimally processed fruits for
      25 days at 4 degrees C, possibly as a result of an enhanced antioxidative action
      of the ascorbate-peroxidase complex and trace metal ion cofactors.

PMID- 10907238
TI  - Interactions of flavor compounds with pectic substances.
AB  - Investigation has been conducted using equilibrium dialysis on the sorption of
      flavor compounds (FC) in solutions of low- and high-esterified pectinates (LEP
      and HEP, respectively). The compounds include 2-acetyl pyridine, 2,3-diethyl
      pyrazine, 2-acetyl thiophene and some normal 2-ketones. A method of direct gas
      chromatographic analysis has been developed for the determination of the FC in
      aqueous solutions at concentrations as low as 10(-3)% v/v. Additional information
      was obtained by the analysis of circular dichroism (CD) and apparent molar heat
      capacity. The results indicate: (1) In LEP solutions, sorption of normal
      aliphatic 2-ketones with chain length greater than C6 presumably proceeds via van
      der Waals interactions between alkyl groups of the 2-ketone and hydrophobic
      regions of the pectinate. The sorption increases with increased alkyl chain
      length. The Gibbs energy of the methylene group transferring from the solvent to
      the LEP solution is found to be 1.8 kJ/mol for 2-ketones at C7-C9. (2) In acidic
      media, binding of heterocyclic FC with pectinates mostly proceeds via hydrogen
      bonding involving the hydrogen atoms in undissociated carboxyl groups in the
      pectinate macromolecules. It can also be affected by the self-association of the
      pectinate macromolecules, depending on pH and pectinate concentration. (3) Under
      neutral conditions, the presence of Mg2+, Ca2 and Zn2+ ions or the formation of
      the calcium-pectinate gel network has little effect on the sorption of 2-ketones
      with the LEP. However, in acidic media, metal ions inhibit the sorption of FC
      through hydrogen bonding. The sorption of 2-octanone in acidic media depends
      extremely on Ca++ concentration by the correlationship with changes in the
      structure of LEP solutions in terms of apparent molar heat capacity.

PMID- 10907240
TI  - The effect of red beet (Beta vulgaris var. rubra) fiber on alimentary
      hypercholesterolemia and chemically induced colon carcinogenesis in rats.
AB  - The effect of diet supplemented with 5% and 15% cellulose or with 15% fiber
      isolated from red beet (Beta vulgaris var. rubra) on the development of
      alimentary hypercholesterolemia and chemically induced colon carcinoma was
      studied in male Wistar rats. Hypercholesterolemia was induced by a diet
      containing 0.3% of cholesterol and colon carcinoma was induced by treatment with
      dimethylhydrazine (20 mg/kg, 12 doses applied s.c. in one-week intervals).
      Fibrous matter isolated from red beet contained 89% fiber, of which 9% was in
      water soluble form. Animals were killed 14 weeks after the application of
      dimethylhydrazine (i.e. 26 weeks after starting on the diets). Red beet fiber
      diet (and not the increased cellulose intake) caused a reduction of serum
      cholesterol and triacylglycerol levels (by 30 and 40%, respectively) and a
      significant increase in the fraction of cholesterol carried in HDL. This diet
      induced also a significant decrease (almost by 30%) of cholesterol content in
      aorta. Higher cellulose content in the diet and even more so the administration
      of red beet fiber caused a significant reduction of conjugated dienes content in
      plasma, erythrocytes and in liver. Also observed were increases in the activities
      of superoxide dismutase and catalase in erythrocytes and in colon and activities
      of glutathione peroxidase and glutathione-S-transferase in liver. The presence of
      both higher cellulose content and red beet fiber in the diet significantly
      reduced the incidence of precancerous lesions--aberrant crypt foci--in the colon.
      The diet containing red beet fiber did not affect significantly the incidence of
      colon tumours although the number of animals bearing tumours was reduced by 30%.

PMID- 10907239
TI  - Unfolding of multimeric proteins in presence of denaturants. A case study of
      helianthinin from Helianthus annuus L.
AB  - Helianthinin (11S), a multisubunit protein from Sunflower Seeds (Helianthus
      annuus L.) dissociates to its monomer (2S) through a trimeric (7S) intermediate
      as a function of guanidine hydrochloride (GuHCl) and guanidine thiocyanate
      (GuHSCN) concentration. Measurements of viscosity, velocity sedimentation
      patterns and spectroscopic parameters of the protein in presence of these
      denaturants both at equilibrium and as a function of time clearly suggest that
      the dissociation, unfolding and aggregation of this multimeric protein occur
      sequentially. The unfolding of the protein in guanidinium salts has two
      transitions with the first transition occurring between native to intermediate
      and the second transition occurring between intermediate state and unfolded
      state. The midpoint concentration for the major transition is 1.75 M for GuHCl
      and 0.8 M for GuHSCN. Evaluation of this data suggests that during the process of
      denaturation the simultaneous unfolding of acidic and basic subunits of the
      protein takes place. At intermediate concentrations of denaturant namely 1.6 M of
      GuHCl or 1.1 M of GuHSCN the aggregation of the protein was found to be maximum.
      The results suggests the possibility of a mechanism for the dissociation,
      denaturation and unfolding of multimeric proteins in presence of the chemical
      denaturants.

PMID- 10907241
TI  - Effect of amino acids on the composition and properties of extruded mixtures of
      wheat flour and glucose.
AB  - Wheat flour was extruded at 100-120 degrees C with 5% D-glucose or mixtures of 5%
      D-glucose and 0.5% or 2.0% of L-alanine, L-leucine, L-lysine, L-threonine or L
      cysteine. The extent of browning was only moderate, and yellow and red pigments
      were produced. The odour intensity increased with the addition of either glucose
      or a mixture of glucose and amino acids; the odour was not significantly
      intensive according to sensory acceptancy analysis. The odour profile was
      influenced by the structure of amino acid present in the extruded material. The
      addition of D-glucose increased the production of furan derivatives, and in
      lesser degree, of pyrazines in the extruded product. The pyrazine content
      increased with the addition of amino acids, except cysteine which enhanced the
      production of sulphur compounds instead of pyrazines. The composition of the
      pyrazine fraction varied depending on the amino acid added. Pretreatment of D
      glucose with an amino acid in aqueous solution affected the composition of
      volatiles, but it did not significantly enhance the pyrazine production.

PMID- 10907242
TI  - Formation of protein bound lysine-derived galactosyl and glucosyl pyrroles in
      heated model systems.
AB  - Residues of lysine-substituted AGEs (advanced glycosylation end-products) arising
      from the Maillard reaction and containing the carbon backbone of lactose or
      maltose, thus deriving from 1-desoxy-ketose degradation, were produced when
      casein was heated in the presence of the corresponding U14C labelled
      disaccharides. The enzymatic hydrolysates of the washed casein were purified by
      SPE and submitted to HPLC on a C18 column flushed with diluted acetic acid. A
      specific chromatographic peak (lambda max, 288.1 nm; MW, 416.2 Da) with a
      different retention time was obtained for each disaccharide reacted. On the basis
      of the value of the specific radioactivity, the two compounds appeared to contain
      the whole carbon backbone of the parent sugar. Analyses by MS/MS and NMR
      performed on the same two compounds extracted at preparative scale from lysine
      lactose and lysine-maltose model systems allowed the structure assignment of 6-[2
      acetyl-3-(beta-D-galactopyranosyloxy)-1-pyrrolyl] 2-amino hexanoic acid and 6-[2
      acetyl-3-(alpha-D-glucopyranosyloxy)-1-pyrrolyl] 2-amino hexanoic acid,
      respectively. Both compounds submitted to enzymatic deglycosylation by specific
      alpha- or beta-glucosidases produced the lysine-derived acetyl pyrrole 6-(2
      acetyl-3-hydroxy-1-pyrrolyl) 2-amino hexanoic acid (lambda max, 288.1 nm; MW,
      254.1 Da). Galactosyl- and glucosyl-isomaltoles, extracted from the lysine
      containing systems, identified with the reference molecules and heated in the
      presence of lysine under slightly alkaline conditions, gave the expected lysine
      derived glycosyl pyrroles as identified above. The HPLC conditions were optimized
      by adjusting the composition of the eluting solvent and temperature of the column
      to achieve the best separation and identification of the AGEs in mixtures such as
      foods with possible interfering molecules like Trp and lysyl pyrrole aldehyde.
      Because of the reported presence of the two precursors isomaltol glycosydes in
      some foods, the corresponding lysine-derived glycosyl pyrroles can occur as both
      protein bound and in free form.

PMID- 10907244
TI  - Biosynthesis of nutraceutical iso-oligosaccharides by multiple forms of
      transferase produced by Aspergillus foetidus.
AB  - Isomalto-oligosaccharide and isofructo-oligosaccharide production was attempted
      using enzymes produced by Aspergillus foetidus. Four fractions having transferase
      enzyme activity were obtained from the fermentation broth of Aspergillus foetidus
      by ammonium sulfate precipitation and DEAE-cellulose chromatography. The optimum
      temperature was 60 degrees C and pH stability in the range 4 to 6 for various
      fractions. The pH optima, heat sensitivity and kinetic parameters for the four
      fractions were however not the same. All four enzyme fractions could not utilize
      lactose and cellobiose to synthesize isooligosaccharide and showed different
      transferase activity for maltose and sucrose for synthesis of
      isooligosaccharides. The HPLC isooligosaccharide product analysis of these
      transferase enzymes reveal that the four forms of enzymes are distinct and
      produce oligosaccharides like panose, kestose and nystose or act as hydrolytic
      enzymes, depending on reaction conditions.

PMID- 10907245
TI  - Effects of xanthan and galactomannan on the freeze/thaw properties of starch
      gels.
AB  - Three starches (maize, rice and wheat), and the two non-starch polysaccharides
      xanthan and locust bean gum galactomannan (LBG) were examined in gel and dough
      systems for texture and stability properties during freezing and low temperature
      storage. Xanthan and LBG were found to confer increased resistance to freeze/thaw
      cycling on rice starch gels but the non-starch polysaccharides had little effect
      on the performance of maize and wheat starch gels or on wheat dough.

PMID- 10907243
TI  - Multi-functional biopolymer prepared by covalent attachment of galactomannan to
      egg-white proteins through naturally occurring Maillard reaction.
AB  - Protein-polysaccharide conjugate was prepared as a functional biopolymer using
      protein and polysaccharide via a Maillard-type reaction. Ovalbumin and lysozyme
      were conjugated with galactomannan under controlled heating and humidity
      conditions. The antioxidant effect of ovalbumin and the antimicrobial activity of
      lysozyme were enhanced by the glycosylation. The emulsifying properties of the
      egg protein were also significantly improved by the modification. The increase in
      lipid affinity due to the conjugation resulted in the enhancement of the radical
      scavenging ability of ovalbumin. The effectiveness of lysozyme and its
      glycosylated derivative in restricting the activity of a Gram-negative pathogen,
      Edwardsiella tarda in fish was also investigated.

PMID- 10907246
TI  - Glycosidase inhibitors and their chemotherapeutic value, Part 3.
AB  - The various compounds that have been investigated as glycosidase inhibitors are
      reviewed. The last one of three parts of this review article covers the following
      classes of compounds: amidines, amidrazones, amidoximes, sugars with sulphur in
      the ring, carba sugars, pseudo oligosaccharides, cyclitols and trehazolamine
      analogues, fused heterocycles and trehazolin analogues, dioxane derivatives, open
      chain compounds, heterocyclic compounds with hydroxyalkyl residues, aromatic
      compounds, amino acids and other derivatives.

PMID- 10907248
TI  - New 1,3-benzoxazin-2-ones or thiones of molluscacidal activity.
AB  - A facile synthetic approach towards 3-aryl, alkyl or beta-glucopyranosyl-1,3
      benzoxazin-2-ones and their thio-analogues 3 was adopted via the reaction of the
      easily available 3-(2-hydroxyaryl)-2-propen-1-ones 1 with a variety of
      isocyanates or isothiocyanates. The isolation of the open-chain carbamates 2 and
      then independent cyclization to the corresponding 1,3-benzoxazines 3 confirms the
      reaction sequence. Molluscacidal activity of the products was screened.

PMID- 10907247
TI  - Synthesis and preliminary screening of derivatives of 2-(4-arylpiperazin-1
      ylalkyl)-3-oxoisothiazolo[5,4-b] pyridines as CNS and antimycobacterial agents.
AB  - We have synthesized several new isothiazolopyridines possessing a side chain at
      the isothiazole ring typical, among others, for trazodone or NAN-195.
      Representatives of the novel isothiazolopyridines were examined for acute
      toxicity and in several commonly used CNS tests in mice and for arterial blood
      pressure in rats. Three of the five compounds tested showed significant analgesic
      activity. The most active compound (3b) exhibited analgesic action in the
      "writhing" test in a dose 1/1280 of LD50 (LD50 = 1135.5 mg/kg) after
      administration i.p. to mice. Additionally, the compounds described here and
      related isothiazolopyridines obtained previously were evaluated against
      Mycobacterium tuberculosis H37Rv at 12.5 micrograms/ml in in vitro assays. Seven
      of the nineteen compounds tested showed 100% inhibition of that mycobacterium.

PMID- 10907249
TI  - Synthesis of 6,7-dialkoxy-2-arylmethylidene-2,3- dihydrobenzo[4,5]imidazo[2,1
      b][1,3]thiazol-3-ones exhibiting anti-inflammatory activity.
AB  - New 6,7-dialkoxy-2-arylmethylidene-2,3- dihydrobenzo[4,5]imidazo[2,1
      b][1,3]thiazol-3-ones (3a-h, 4b, c, e, g) were synthesized from 2-(5,6-dialkoxy
      1H-benzo[d]imidazol-2-ylsulfanyl)acetic acids (1, 2) and corresponding aromatic
      aldehydes in acetic anhydride. The compounds 3e, f and 4b, g were also
      synthesized from corresponding aromatic aldehydes and 6,7-dialkoxy-2,3
      dihydrobenzo[4,5]imidazo[2,1-b][1,3]thiazol -3-ones (5, 6) obtained by the
      cyclization of the acids 1 and 2 in acetic anhydride. The synthesized compounds
      3a-h and 4b, c, e, g exhibit anti-inflammatory activity.

PMID- 10907250
TI  - Application of derivative UV spectrophotometry for the determination of enoxacin
      and nalidixic acid in tablets.
AB  - First-, second-, third- and forth-order derivative spectrophotometric methods,
      using "peak-zero" (P-O) and "peak-peak" (P-P) techniques of measurement have been
      developed for the determination of enoxacin and nalidixic acid in tablets. The
      calibration curves were linear in the concentration range of 2.0-12.0 micrograms
      ml-1 for the analysed quinolones. The procedure was simple, rapid and the results
      were reliable.

PMID- 10907251
TI  - [Determination of dissociation constants of aminomethyl phenols with UV
      spectrometric titration].
AB  - Dissociation constants of phenoles aminomethylated once or twice were determined
      using UV spectrometric titration. Pka values were computed by non linear
      regression; correlation coefficients show that experimental data and calculated
      curves fit well.

PMID- 10907252
TI  - Physico-chemical, in vitro and in vivo characterisation of polymers for ocular
      use.
AB  - The influence of artificial tear fluid (AT) on ionic and nonionic ophthalmic
      polymer excipients was rheologically established. In usual concentrations
      polyvinylalcohol, polyvinylpyrrolidone, dextran, hydroxypropylmethylcellulose,
      hydroxyethylcellulose and methylcellulose did not show any changes. In contrast,
      solutions of polyacrylic acid, sodium hyaluronate (S-Hya), sodium alginate (S
      Alg) and chitosan decrease the apparent viscosity in contact with AT, while
      gellan solution increases the viscosity and shows thixotropy. The adhesion of
      selected polymers (polysaccharides) on mucin was evaluated using a rheological
      method and resulted in the order S-Hya > Gellan > S-Alg > dextran. Miosis testing
      of Gellan containing pilocarpine HCl formulations in rabbits shows a possible
      reduction of drug concentration from 2% to 0.5% obtaining the same
      bioavailability.

PMID- 10907253
TI  - Hot melt coating technology: influence of Compritol 888 Ato and granule size on
      chloroquine release.
AB  - The tangential spray technique was used to coat chloroquine granules with
      Compritol 888 Ato in a fluidized bed (Glatt GPCG-1,1). After validation of the
      assay method for chloroquine, dissolution tests were carried out on four size
      fractions obtained from the same batch of granules. The dissolution profiles
      obtained showed differences in the rate of release between one fraction and
      another, despite the fact that each of these fractions had been coated with the
      same quantity of wax. This suggests that the rate of release of the chloroquine
      may be adjusted by controlling the size of the granules. Furthermore these
      dissolution profiles were characterized by a rapid release phase followed by a
      slow release phase. Examination of the surfaces of the granules from the various
      size fractions under a scanning electron microscope revealed that Compritol did
      not form a continuous film but existed rather as a lipid environment around the
      granule. This lipid environment was made up of solidified droplets of the wax
      which had become piled up on the surface of the granule. Compression of the
      granules produced tablets which remained intact until chloroquine dissolution was
      complete. This undicated that the active substance diffused across the Compritol
      matrix generated during compression. Determination of the dissolution kinetics
      using the Higuchi model demonstrated the diffusion release mechanism.

PMID- 10907254
TI  - ["Non-solvent shock agglomeration"--the technology of a new alternative method
      for determination of ibuprofen. 6. Stability of s(+)-ibuprofen].
AB  - Due to its low melting range approx. 53 degrees C optically pure ibuprofen can be
      regarded as problematic in a pharmaceutic-technological sense. With regard to the
      non-solvent shock agglomeration method this means that the process and product
      temperatures must strictly be kept in the range of 10 K above the melting point
      of the substance. Higher temperatures can induce degradation of S(+)ibuprofen.
      During storage under stress conditions (31 degrees C for a period of 18 months)
      ibuprofen shows extreme stability independent of its optical activity. Racemic
      ibuprofen is inert to the influence of light; in individual cases optically pure
      substance containing an increased level of impurities can show slight degradation
      tendencies. The thermal and photo stability of ibuprofen is independent of the
      preparation technology. For comparison, conventional, fluid bed granulated,
      briquetted and from organic solvents especially recrystallised and optically
      active substances were investigated besides the shock agglomerated substances.

PMID- 10907255
TI  - The treatment of delayed polyneuropathy induced by diisopropylfluorophosphate in
      hens.
AB  - This study was undertaken to examine the influence of atropine, oximes and
      benzodiazepine on organophosphate-induced delayed polyneuropathy (OPIDP) in hens,
      which were poisoned with diisopropylfluorophosphate (DFP). The birds were treated
      with a standard neuropathic dose of DFP (1.1 mg/kg, s.c.), which produced typical
      signs of OPIDP. The development of OPIDP was observed within the followings 22
      days. All drugs were given subcutaneously (s.c.), intramuscularly (i.m.) or
      intraperitoneally (i.p.), 20 min before the poison. The results obtained have
      shown that atropine (20 mg/kg, i.p.) only in combination with oxime TMB-4 (15
      mg/kg, i.m.) produced significant improvement of OPIDP symptoms in comparison
      with positive control. Clinical signs and symptoms of OPIDP in the group which
      was treated with atropine (20 mg/kg, i.p.), TMB-4 (15 mg/kg, i.m.) and midazolam
      (2.5 mg/kg, i.m.) were more improved than that in the presence of a combination
      of atropine and TMB-4. The results of these experiments have shown that it is
      possible to prevent the development of DFP-induced OPIDP in hens by treatment
      with atropine and TMB-4 or atropine, TMB-4 and midazolam when given before DFP.

PMID- 10907256
TI  - [Enantiomeric monoterpenes in ether oil from Achillea millefolium s. I.--a
      taxonomically useful marker?].
AB  - The Achillea millefolium complex is a group of taxonomically hardly separable
      species. Yarrow has the tendency to hybridize and to vary in phenotype. An
      obvious characterization of the species or hybrids is not just important for the
      taxonomical distinction but also for a reliable assessment of herbal drug
      quality. Most of the Achillea plants are still gathered from natural populations.
      According to the variation in phenotype, mixtures with Achillea species, which
      contain allergy setting compounds, often cannot be determined. Morphometric
      investigations exclusively do not replace a further chemical characterization.
      Therefore we tried to assess the composition of the chiral monoterpenes alpha
      pinene, beta-pinene and sabinene. They were selected because of their frequency
      in the essential oil of Achillea species. By method of M.C.S.S. (Moving Capillary
      Stream Switching) the differentiation of stereoisomeres succeeded directly from
      the essential oil, which was distilled or extracted by headspace trapping at room
      temperature. The enantiomeric distribution neither depends on the method of
      extraction, nor on the habitat or the developmental stage of Yarrow. Since the
      compositions of enantiomeres from several Achillea species and their hybrides are
      of different pattern, it seemed to represent an additional marker. Though
      investigations of all species within the Achillea millefolium group and possibly
      of further chiral compounds are necessary to ensure these results.

PMID- 10907257
TI  - Triterpenoidal saponins from Cornulaca monacantha.
AB  - From the aerial parts of Cornulaca monacantha, three new triterpenoidal saponins
      have been isolated and their genuine structures were identified as 3-O-[beta
      xylopyranosyl-(1-->3)-beta- glucuronopyranosyl]-30-methylphytolaccagenate (2), 3
      O-[beta-xylopyranosyl- (1-->3)-beta-glucuronopyranosyl]-30-methylphytolaccagenate
      28-O-beta-gluco-pyranoside (3) and 3-O-[beta-xylopyranosyl-(1-->3)-beta-
      glucurono-pyranosyl]-30-methylserjanate 28-O-beta glucopyranoside (4) together
      with nine known saponins of oleanolic acid (5-9), hederagenin (1, 10, 11) and 30
      methyl phytolaccagenate (12).

PMID- 10907258
TI  - [The synthesis of 4-(17 beta-methoxy-17 alpha-(methoxymethyl)-estra-4,-dien-11
      beta-yl)benzaldehyd-1(e)-oxime].

PMID- 10907259
TI  - HPLC determination of caffeine in a multicomponent preparation.

PMID- 10907260
TI  - Measurement of film thickness on the surface of coated pellets and its influence
      on drug dissolution rate.

PMID- 10907261
TI  - The synergistic effect of laurocapram pretreatment and iontophoresis on the
      percutaneous permeation of non-steroidal anti-inflammatory drugs in vitro.

PMID- 10907262
TI  - [Titanium blood levels of dialysis patients compared to healthy volunteers].

PMID- 10907263
TI  - Influence of dopaminergic anti-Parkinsonian agents on inflammatory reactions in
      rats.

PMID- 10907264
TI  - Cyclocitrinol, a new fungal metabolite from Penicillium citrinum.

PMID- 10907266
TI  - Education and training in health promotion and health education: trends,
      challenges and critical issues.

PMID- 10907265
TI  - Alkaloids and bioactivity of Papaver triniifolium.

PMID- 10907267
TI  - The landscape in health education and health promotion training.

PMID- 10907268
TI  - The EUMAHP project--the development of a European masters programme in health
      promotion.

PMID- 10907269
TI  - Training in health promotion and health education in Latin America.

PMID- 10907270
TI  - Riding the new wave: strengthening education for health promotion in Pacific
      Island countries.

PMID- 10907271
TI  - Health promotion curricula: cross-national comparisons of essential reading.

PMID- 10907272
TI  - Development of competency-based university health promotion courses.

PMID- 10907273
TI  - Developing competencies for health promotion training in Aotearoa-New Zealand.

PMID- 10907275
TI  - The technology corner.

PMID- 10907274
TI  - Health promotion practice, research and policy: building capacity through the
      development of an interdisciplinary study centre and graduate programme in
      Alberta, Canada.

PMID- 10907276
TI  - Potential effects on fertility and child health and survival of birth-spacing
      preferences in sub-Saharan Africa.
AB  - Using Demographic and Health Survey data from 20 sub-Saharan African countries,
      this article compares the actual lengths of birth intervals to women's reported
      preferred lengths, and assesses the implications of the difference between the
      two for selected demographic and health indicators. The results show a clear
      pattern. In Comoros, Ghana, Kenya, Rwanda, and Zimbabwe, women prefer much longer
      birth intervals than those they actually have, compared with women in the other
      15 countries studied. As a consequence, the potential effects of spacing
      preferences on the level of fertility and on the prevalences of short (less than
      24 months) birth intervals and child malnutrition are greatest in the same five
      countries. The covariates of preferred birth-interval lengths are also examined.
      An explanation is offered for this pattern, based on the observed sharp decline
      in fertility recently experienced by these five "forerunners." In general, women
      who know, approve of, discuss, and use family planning prefer longer intervals
      than do their counterparts. The policy and program relevance of these results is
      discussed.

PMID- 10907277
TI  - An assessment of DHS maternal mortality indicators.
AB  - This study presents an assessment of the quality of data relating to maternal
      mortality collected in 14 Demographic and Health Surveys (DHS) for 13 countries
      that included a complete sibling history. Four aspects of data quality are
      considered: completeness of the data for reported events, evidence of omission in
      the reporting of events, plausibility of the pattern of sibling deaths, and
      sampling errors of the maternal mortality estimates. Although the data relating
      to reported events are complete for most variables, comparisons of sibling
      history-based estimates of adult mortality for both males and females with other
      independent estimates suggest that sibling estimates are more likely to be
      underestimates than overestimates. The downward bias is probably greater for
      female mortality than for male mortality. The sampling errors associated with
      maternal mortality ratios are substantially larger than those associated with
      other frequently used DHS indicators. This lack of precision precludes the use of
      these data for trend analysis and has led to the recommendation that this DHS
      module not be used more than once every ten years in the same country.

PMID- 10907278
TI  - The role of couple negotiation in unmet need for contraception and the decision
      to stop childbearing in Uganda.
AB  - This study uses survey and focus-group data from the 1995-96 Negotiating
      Reproductive Outcomes study in Uganda to describe the nature of the decision to
      stop childbearing and to question the simplifying assumption of consensus
      decision-making implicit in much demographic research on unmet need. Negotiation
      is characterized in four stages, from normative precedent for decision-making to
      communication, disagreement, and conflict resolution. Indirect forms of
      communication between partners predominate, contributing to the tendency of both
      men and women to overestimate each other's demand for additional children.
      Partner opposition is found to cause a statistically significant increase in
      unmet need reported by women and a shift in contraceptive mix favoring use of
      traditional methods over modern methods. For women, partner opposition may
      account for as much as 20 percent of unmet need in urban areas, 12 percent in
      rural areas, and 15 percent overall.

PMID- 10907279
TI  - Developing an interactive STD-prevention program for youth: lessons from a north
      Indian slum.
AB  - An intervention developed to teach young men in the urban slums of Lucknow,
      India, about sexually transmitted diseases is described in detail. This community
      based intervention was designed to impart core educational messages and to
      address preexisting ideas about sexual health and STD-prevention practices among
      participants. Indicators of knowledge recorded before and after the intervention
      are presented and evaluated against the scores of a control group. Levels of
      sexual activity and factors associated with risky sex are discussed. The
      intervention was successful in raising the young men's awareness of STDs
      significantly in all areas except for the length of time that symptoms take to
      manifest following risky sex and the ineffectiveness of washing one's genitals
      after sex to avoid acquiring STDs. Lessons learned during the intervention are
      described as a means of informing future STD-education programs, and issues
      requiring prompt attention are identified.

PMID- 10907280
TI  - Implementing the integration of component services for reproductive health.
AB  - In the wake of the 1994 International Conference on Population and Development in
      Cairo, considerable activity has occurred both in national policymaking for
      reproductive health and in research on the implementation of the Cairo Program of
      Action. This report considers how effectively a key component of the Cairo agenda
      -integration of the management of sexually transmitted infections, including
      human immunodeficiency virus, with maternal and child health-family planning
      services--has been implemented. Quantitative and qualitative data are used to
      illuminate the difficulties faced by implementers of reproductive health programs
      in Ghana, Kenya, South Africa, and Zambia. In these countries, clear evidence is
      found of a critical need to reexamine the continuing focus on family planning
      services and the nature of the processes by which managers implement reproductive
      health policies. Implications of findings for policy and program direction are
      discussed.

PMID- 10907281
TI  - How well do perceptions of family planning service quality correspond to
      objective measures? Evidence from Tanzania.
AB  - This study examines the relationship between common objective measures of quality
      and perceptions of the quality of family planning facilities. Results of prior
      research indicate that such perceptions are an important determinant of
      contraceptive use in rural Tanzania. The data for this study are drawn from two
      surveys conducted in rural Tanzania. Three models are tested separately for women
      and for men. The important determinants of perceptions of quality among women and
      men are: perceived travel time to the facility, availability of immunizations,
      and availability of maternal and child health services. Additionally, the ratio
      of the number of staff to outpatients is important to men. The data explain a
      moderate amount of the variance in the quality measures, indicating that
      perceived quality is not fully predicted by common objective measures of quality.
      Future surveys of facility quality should develop objective measures to better
      predict the perceived quality, with the underlying goal of increasing
      contraceptive use.

PMID- 10907282
TI  - Nicaragua 1998: results from the Demographic and Health Survey.

PMID- 10907283
TI  - Philippines 1998: results from the Demographic and Health Survey.

PMID- 10907285
TI  - Investigations on the prevalence of bovine tuberculosis and brucellosis in dairy
      cattle in Dar es Salaam region and in zebu cattle in Lugoba area, Tanzania.
AB  - A study between August 1995 and December 1997 included 343 dairy cattle on 20
      farms in the Dar es Salaam region and 2289 zebu cattle on 39 bomas in the Lugoba
      area (coast region). The aim was to establish the prevalence of bovine
      tuberculosis (Mycobacterium bovis) and bovine brucellosis (Brucella abortus). In
      the single intradermal tuberculin test (SIT), 0.9% (3/343) of the animals in Dar
      es Salaam tested positive and 1.2% (4/343) were doubtful. Positive reactors were
      found in 10% (2/20) of the farms. In the Lugoba area, 0.6% (14/2206) were
      positive and 6.8% (149/2206) doubtful, positive cases being found in 21% (8/39)
      of all bomas. In the slow agglutination test (SAT) for B. abortus, 14.1% (48/341)
      of the serum samples reacted positively in Dar es Salaam and 2.3% (8/341) were
      doubtful. Positive SAT reactors were identified on 25% (5/20) of the dairy cattle
      farms. In the Lugoba area, 12.3% (273/2221) proved to be positive SAT reactors
      and doubtful reactions were observed in 2.9% (64/2221). SAT-positive animals were
      detected on 87% (34/39) of all bomas. The prevalence in single herds in Dar es
      Salaam varied from 4.3% to 5.3% for the SIT and from 2.2% to 50% for the SAT. The
      prevalence in single herds in Lugoba area was between 1.1% and 2.9% for SIT and
      from 1.4% up to 62.1% for SAT. The two cattle populations differed significantly
      (p < 0.001) in the prevalence of both bovine tuberculosis and bovine brucellosis.
      Two cows that were positive reactors were slaughtered and subjected to post
      mortem examination, and organ samples were bacteriologically cultured. The
      occurrence of Mycobacterium tuberculosis was confirmed by polymerase chain
      reaction (PCR) in both cows.

PMID- 10907284
TI  - Diagnosis of rinderpest in Tanzania by a rapid chromatographic strip-test.
AB  - A simple chromatographic strip-test based on Clearview technology, is under
      development as a pen-side test for the detection of rinderpest antigen in eye
      swabs taken from cattle in the field. An outbreak of rinderpest occurred in the
      northern zone of Tanzania from late February to June 1997. The affected cattle
      exhibited very mild clinical signs, which made clinical diagnosis difficult. One
      hundred and seven eye swabs were collected from cattle suspected of infection
      with rinderpest. These were tested in the field using a prototype of the pen-side
      test and 13 (12.15%) of the samples were found to be positive for the presence of
      rinderpest antigen. These were confirmed by ICE. The positive cases were
      predominantly found in the Ngorongoro district. This demonstrates the usefulness
      of such a simple, rapid pen-side diagnostic assay, particularly when clinically
      'mild' strains of rinderpest are present.

PMID- 10907286
TI  - Comparative evaluation of a field-based dot-ELISA kit with three other
      serological tests for the detection of Brucella antibodies in goats.
AB  - A dot-ELISA (d-ELISA) test was evaluated and compared with the serum
      agglutination test (SAT), micro-complement fixation test (CFT) and a plate-ELISA
      (p-ELISA) for field use in screening herds of goats against brucellosis. During
      the standardization of the dot-ELISA kit on 1732 caprine serum samples, 1571
      samples out of 1666 were found to be negative in d-ELISA, SAT and micro-CFT,
      while 59 were positive in different combinations. Of a further 66 serum samples,
      34 were negative and 31 were positive in different combinations in d-ELISA, SAT,
      micro-CFT and p-ELISA. A total of 1584 goats belonging to different herds were
      then screened for brucellosis. Of the 694 serum samples screened in the first
      batch using d-ELISA, a positive reaction was observed in 26 cases. Further
      screening of these cases revealed 13 and 21 goats as positive reactors in SAT and
      CFT, respectively. In a second batch of 890 goats there were 109 positive
      reactors in d-ELISA. Among these 109 goats, 34, 40 and 80 goats were positive
      reactors in SAT, CFT and p-ELISA, respectively. The results of d-ELISA correlated
      well with those of p-ELISA. Dot-ELISA was found to be a more suitable and rapid
      test for screening large numbers of goats in the field.

PMID- 10907287
TI  - An outbreak of gangrenous syndrome among buffaloes and cattle in West Bengal:
      clinicopathological studies.
AB  - Gangrenous syndrome/Degnala disease was recorded in a large number of buffaloes
      and cattle in Murshidabad district of West Bengal, India. Fusarium spp. had been
      isolated from the mouldy paddy straw which were fed to the animals. There was a
      reduction in the incidence of the disease following withdrawal of the mouldy
      paddy straw. Histopathological examination showed necrosis and loss of
      architectural details in the skin.

PMID- 10907288
TI  - Rocket immunoelectrophoresis in the diagnosis of infectious bursal disease.
AB  - The rocket immunoelectrophoresis (RIE) test was used for the qualitative
      detection and quantitative estimation of infectious bursal disease virus (IBDV)
      specific antigen in experimentally infected chickens and samples collected from
      suspected outbreaks. The IBDV specific antigen was detected in the bursae of
      experimentally inoculated chickens up to 5 days post infection (PI) by the agar
      gel precipitation (AGP) test and 7 days PI by the RIE test. The RIE detected IBDV
      specific antigen in a significantly greater number of samples collected from the
      field outbreaks than the conventional AGP test. Exudative bursae were found to
      have a higher antigen content than haemorrhagic bursae and are recommended as the
      material of choice for diagnosis of IBD. This test could also be used to quantify
      IBDV specific antigen in commercial killed vaccines.

PMID- 10907289
TI  - Evaluation of a filter paper blood sampling technique for quantitative assessment
      of antibodies to infectious bursal disease virus.

PMID- 10907290
TI  - Antigenetically unusual Newcastle disease virus from racing pigeons in India.
AB  - Newcastle disease virus isolated from an outbreak in racing pigeons in India was
      found to be velogenic, based on the mean time to death in 10-day-old embryonated
      hen's eggs, the intravenous pathogenicity index in 6-week-old chickens and the
      pathogenesis in chickens and pigeons. The virus induced disease in chickens
      without prior adaptation in chickens. The virus was antigenically unusual since
      it could not be grouped with the available panel of monoclonal antibodies at the
      World Reference Laboratory for Newcastle disease, UK. However, commercially
      available lentogenic and mesogenic vaccines provided 100% protection to chickens
      against this antigenically unusual NDV.

PMID- 10907291
TI  - A comparative economic analysis of smallholder cattle and small ruminant
      production systems in Botswana.
AB  - Cattle rearing is the single most important activity in the agricultural sector
      of Botswana, and cattle enjoy a high status among both rural and urban dwellers.
      In recent years, farmers have begun to intensify the production of small
      ruminants owing to an increasing recognition by policy makers that they are a
      potential alternative source of farm income. However, as yet, small ruminants
      have not approached the social importance of cattle. This may be attributable to
      several factors, including economic considerations. The present study focused on
      the economic factor. It comprised a comparative economic assessment of cattle-
      and goat-rearing enterprises for an average smallholder farm-household to throw
      light on their relative economic efficiency. It was concluded that rearing either
      cattle or small ruminants is economically viable in the study area. The net
      profit measured as the net margin either per enterprise or per animal was far
      higher for a cattle-rearing enterprise. Nevertheless, when expressed in terms of
      the return on the capital invested in each enterprise, cattle rearing had only a
      slight edge (1.93%) over rearing of small ruminants.

PMID- 10907292
TI  - Effect of parity, season and FSH treatment on the calving interval of Ayrshire
      cows in the tropics.
AB  - A total of 607 calving intervals on 99 Ayrshire cows with parities from 1 to 10
      and belonging to one dairy herd at Iringa in the southern highlands of Tanzania
      were analysed to study the effect of parity and season or month of calving on the
      subsequent calving interval. In addition, 22 calving intervals incorporating a
      superovulatory cycle were compared with those of 52 controls that had calved
      around the same period. The average (mean +/- SEM) age at first calving was 985
      +/- 16 days. The effect of parity on calving interval was highly significant (p <
      0.001). Cows that calved in December, at the beginning of the rainy season,
      exhibited the shortest calving interval (404 +/- 13), while those that calved in
      September/October, in the dry season, exhibited the longest average calving
      interval (466 +/- 20 days), although this difference was not significant. Prior
      treatment with follicle-stimulating hormone to induce superovulation,
      significantly lengthened the average calving interval (579 +/- 28 vs 457 +/- 15
      days; p < 0.001). It was concluded that both parity and FSH treatment affected
      the calving interval. However, season (rainy vs dry) or month of calving did not
      influence this interval.

PMID- 10907293
TI  - [Development and current status of invasive coronary angiography].
AB  - Invasive selective coronary angiography as a clinical method is about 40 years
      old. This article surveying this period, written by an R&D engineer, deals with
      four parts: first the situation before 1965 is touched upon. For the time after
      1965 the second and third parts describe the development of the procedure and of
      the technique with special reference to the work of Prof. Dr. K. Bachmann and to
      the facility, which in 1967 was designed together with him and further developed.
      K. Bachmann had already taken up the method of invasive coronary angiography
      around 1965, which makes him one of the group of pioneering users who developed
      the fundamentals of the procedure and led coronary angiography to its self
      evident use today. The first clinical application of high resolution image
      intensifier with the input screen produced from evaporated cesium iodide in 1971
      appears as one of the highlights of the continuous improvements of the facility.
      The fourth part of the article sketches the status of today and, considering the
      new methods using MRI, EBCT as well as CT, it predicts that the invasive coronary
      angiography will remain an indispensable method at least for the medium-term
      future.

PMID- 10907294
TI  - [Intracoronary ultrasound].
AB  - IVUS imaging provides a 2-dimensional, cross-sectional view into the lumen and
      vessel wall structure of coronary arteries; it is superior to angiography with
      regard to visualization about several aspects of coronary artery disease. IVUS
      has given important information on the development and progression of coronary
      atherosclerosis. Moreover, IVUS has improved our understanding of the mechanisms
      of percutaneous interventions and restenosis. IVUS-guided balloon sizing during
      PTCA may increase acute lumen gain as compared to conventional angiographic
      guidance. Optimization of stent implantation by IVUS guidance also results in
      larger initial lumen gain than with angiographic control; this approach, however,
      does not reduce restenosis rates. In summary, IVUS is an optional imaging
      modality that provides clinically useful information in selected patients.

PMID- 10907295
TI  - [Noninvasive imaging of coronary arteries with electron beam tomography (EBCT)].
AB  - Coronary angiography remains the diagnostic standard for establishing the
      presence, site, and severity of coronary artery disease. Electron beam computed
      tomography (EBCT), a non-invasive imaging method with very high spatial and
      temporal resolution, is well suited for cardiac imaging. Using a standard
      protocol, EBCT permits the visualization of the coronary arteries. Stenoses and
      occlusions of the native arteries and of coronary artery bypass grafts can be
      reliably diagnosed. Extremely calcified segments have to be excluded from
      evaluation. Reduced image quality, mainly due to fast vessel motion and
      superposition of large veins, impairs the results obtained for the right and left
      circumflex coronary artery. Possible clinical applications are the follow-up
      after angioplasty (PTCA without stent) and bypass surgery, the exclusion of
      coronary artery disease in patients with low likelihood of disease, and the
      evaluation of coronary anomalies.

PMID- 10907296
TI  - Imaging of the coronary arteries using magnetic resonance angiography.
AB  - Magnetic resonance imaging of the coronary arteries is difficult due to the
      tortuous course of these vessels, their small diameter, and their rapid movement
      caused by respiration and cardiac contraction. Initial investigations could
      demonstrate the feasibility of non-invasive magnetic resonance coronary
      angiography using 2-dimensional turbo-FLASH gradient-echo sequences in repeated
      breathholds of approximately 16 heart beats duration. Further developments,
      especially the design of navigator-echo-based respiratory gated 3-dimensional
      imaging sequences, permitted the acquisition of contiguous volume data sets of
      the heart which eliminated many limitations of 2-dimensional repeated breathhold
      sequences. With a spatial resolution of approximately 1.2 x 1.2 x 2 mm and a
      temporal resolution of approximately 126 ms, several authors reported
      sensitivities of 70-80% and specificities of approximately 90% for the detection
      of coronary artery stenoses. Further improvements can be expected from new,
      intravascular contrast agents and from ultrafast sequences which permit
      acquisition of a sufficiently large imaging volume within one single breathold.

PMID- 10907297
TI  - [Intravenous coronary angiography with synchrotron radiation].
AB  - INTRODUCTION: Coronary artery disease still remains the primary cause of death in
      the western industrialized world. Although the clinical value of selective
      coronary angiography (SCA) is beyond dispute, the associated risk of an invasive
      approach, the inherent costs and the necessary hospitalization have lead to the
      development and investigation of novel non-invasive techniques for coronary
      imaging. Intravenous coronary angiography (ICA) has been shown to permit non
      invasive imaging of the coronary arteries. METHODS: In 66 pts (80% male, age 62
      (+/- 8.5 yrs) after interventional therapy/CABG operation, ICA and a SCA were
      carried out within a time interval of < 6 weeks. After determination of the
      individual circulation time, contrast media (370 mg iodine/ml, 15 ml/s, 21 ml)
      was injected via a sheath in the cubital vein while the patient was sitting in an
      upright position in a specially designed scanning chair. In two different
      projections 6-8 images/patient were obtained for further image processing and
      evaluation. 182 target vessels had to be evaluated (LAD 55, Cfx 21, RCA 54,
      Grafts 52). In 50 target vessels one or more stents were implanted. RESULTS: 182
      target vessels were evaluated according to the following criteria: no stenosis, <
      70%, > = 70%, occlusion. Evaluation of the ICA and SCA images was performed by
      two independent investigators. Due to poor image quality, 17 vessels were not
      evaluated. The ICA findings were compared to that of SCA. For the LAD a
      sensitivity of 84% (specificity 93%), for the RCA a sensitivity of 85%
      (specificity 97%), for the Cfx a sensitivity of 67% (specificity 90%), and for
      grafts a sensitivity of 85% (specificity 97%) was calculated. CONCLUSION: ICA
      proved to be a feasible and safe technique for follow-up after coronary
      intervention/CABG operation on an outpatient basis. Evaluation of stents and
      severe calcification is possible. A good image quality provided, LAD RCA and
      grafts can be evaluated with an acceptable sensitivity and specificity. Due to
      superimpositioning the low sensitivity for the Cfx has to be compensated by
      further image processing.

PMID- 10907298
TI  - [Clinical significance of coronary calcifications in electron beam tomography].
AB  - Electron-beam computed tomography (EBCT) permits high-resolution imaging of the
      beating heart and the coronary arteries and visualization of coronary
      calcification. For clinical purposes, coronary calcification represents the
      formation of atherosclerotic plaques. EBCT provides for accurate quantification
      of calcification, which is itself related to the extent of coronary
      atherosclerosis in a linear fashion. Accordingly, EBCT has been shown to measure
      the extent of coronary atherosclerosis. Importantly, an EBCT scan negative for
      calcification has a high negative predictive value indicating the absence of
      obstructive coronary artery disease and an excellent short- to midterm prognosis.
      It appears that, in general, the amounts of calcification detected by EBCT can be
      used for prospective risk stratification in symptomatic and asymptomatic adults.
      However, data derived from unbiased populations are not available at present, and
      the role of calcification in predicting acute coronary syndromes remains debated.
      Longitudinal EBCT examinations have emerged as another area of substantial
      clinical interest. The clinical value of this method remains to be defined, in
      particular, in comparison with competing, established modalities.

PMID- 10907299
TI  - [Economic aspects of using electron beam computerized tomography].
AB  - Electron beam computed tomography (EBCT) allows visualization and quantification
      of calcium in the coronary arteries. This has been demonstrated to correlate well
      with the overall plaque burden in the coronary arteries. EBCT is, therefore, well
      suited for the detection of early stages of coronary atherosclerosis. Especially
      in asymptomatic patients with several risk factors, staging coronary artery
      disease by coronary calcium, scanning may allow prognostic assessment and guide
      preventive and therapeutic interventions. To date, only scant data are available
      regarding the cost effectiveness and the economic impact of this imaging
      technique. In this manuscript we compare various methods for the diagnosis of
      coronary artery disease using a theoretical model and review the results of a
      prospective trial in our emergency room of coronary calcium scanning in patients
      with acute chest pain. Using Framingham data and prognostic data from long-term
      follow-up, we discuss the impact of coronary calcification scanning on primary
      preventive measures and its economical consequences. EBCT is a promising
      technique which has created a lot of attention due to its ease of application. It
      is currently undergoing critical appraisal in the medical literature. Further
      randomized prospective trials are needed (and underway, i.e., MESA, EDIC, CARDIA
      II) to better define its value and limitations in the clinical arena.

PMID- 10907300
TI  - [Subsecond multislice spiral CT as an alternative to electron beam computerized
      tomography].
AB  - X-ray computed tomography (CT) has exhibited rapid technological advances in
      recent years which has made it a potential alternative to electron beam computed
      tomography (EBCT). In addition to the development of spiral CT, rotation times in
      the subsecond range and the development of multislice detectors were decisive
      steps. These technical developments will be sketched briefly; the necessary
      adaptation of image reconstruction and evaluation will be explained. Particular
      emphasis will be placed on the necessary steps of quality assurance and
      calibration in quantitative procedures, as for example coronary calcium
      measurements. The exposure for typical CT examinations of the heart are in the
      order of half to five times the natural exposure per year. With synchronous
      recording of the ECG, the complete heart can be imaged continuously with thin
      slices and high spatial resolution in less than 30 s. In spite of the very short
      validation phase up to now, we consider multislice spiral CT an alternative to
      EBCT.

PMID- 10907301
TI  - [Myocardial scintigraphy].
AB  - Myocardial scintigraphy allows the assessment of myocardial perfusion and
      viability and has been validated in tens of thousands of patients. This article
      reflects current developments of radiopharmaceuticals as well as of acquisition
      systems; additionally, comparisons are drawn with stress echocardiography and
      myocardial positron emission tomography. Furthermore, the prognostic value and
      the cost-efficiency of this technique are demonstrated.

PMID- 10907302
TI  - [Positron emission tomography].
AB  - Positron emission tomography (PET) is currently the most sophisticated
      scintigraphic imaging technique developed for in-vivo quantification of cardiac
      physiology and biochemistry. The state-of-the-art PET technology allows
      delineation of regional tracer activity with high spatial and temporal
      resolution. A large number of radiopharmaceuticals have been developed to study
      myocardial perfusion enabling accurate diagnosis and localization of coronary
      artery disease (CAD) and energy metabolism. More recently, newer tracers such as
      radiolabeled catecholamine analogues allow the pre- and postsynaptic evaluation
      of cardiac autonomic innervation. Metabolic imaging with PET represents currently
      the gold standard for tissue viability assessment with well-validated diagnostic
      and prognostic information. F-18 deoxyglucose has been also used in combination
      with SPECT or coincidence imaging providing comparable clinical information but
      without need for the expensive and rarely available imaging technology of PET.
      The assessment of coronary flow reserve is the most sensitive scintigraphic
      method to i) detect vascular abnormalities before their hemodynamic significance,
      ii) diagnose and define the extent of CAD, and iii) to monitor the effects of
      (non)pharmacological intervention on regional and global cardiac flow. C-11
      hydroxyephedrine (HED) allows imaging of sympathetic neuronal function. the
      course of cardiac reinnervation after cardiac transplantation was demonstrated
      with C-11 HED PET, and preliminary evidence suggests that this technique might
      provide prognostic information on sympathetic neuronal status in congestive heart
      failure, too. The functional and prognostic relevance of PET imaging together
      with the increased availability of lower cost instrumentation imaging will define
      its future role in the diagnosis, assessment of extent, prognosis and in the
      therapeutic decision making of cardiac disease.

PMID- 10907303
TI  - [Magnetic resonance tomography in clinical cardiology].
AB  - Magnetic resonance imaging (MRI) has become a well-established method for the
      diagnosis of diseases of the heart and the great vessels. Almost 20% of all
      patients cannot be completely examined by transthoracic echocardiography. In this
      patient group, MRI can be used as a second line technique to provide important
      diagnostic information not obtainable by echocardiography. However, there are
      clinical problems for which MRI may be used as the first line technique such as
      complex congenital heart disease, diseases of the great vessels, pericardial
      disease or cardiac tumors. MRI is undergoing rapid technical improvement and this
      will further improve the diagnostic utility of the technique, especially in
      patients with coronary artery disease.

PMID- 10907304
TI  - [Clinical relevance of MR spectroscopy of the heart].
AB  - MR spectroscopy is the only method that allows for the noninvasive study of
      cardiac metabolism in the human heart without the use of external radioactive
      tracers. 31P-spectroscopy allows to examine the high-energy phosphates ATP and
      phosphocreatine. Clinical studies with 31P-spectroscopy have focused on three
      areas: heart failure, valve disease and coronary artery disease. Whether MR
      spectroscopy will become a routine diagnostic tool in the future remains to be
      determined.

PMID- 10907305
TI  - [Stress echocardiography].
AB  - Within the last decade of this millennium, stress echocardiography has been
      established for the diagnosis and follow-up of coronary artery disease. The basis
      is the technical development of the echo machines: first, the improved
      echocardiographic resolution and, second, the digital image storage of a whole
      cineloop, which may be interpreted frame-by-frame in an ECG synchronized manner
      for several exercise levels simultaneously. Myocardial ischemia can be detected
      much earlier by regional contraction abnormalities of the left ventricular
      myocardium than in conventional ECG exercise tolerance testing explaining the
      higher sensitivities. Furthermore, the extent and localization, including the
      correlation with the stenotic coronary anatomy, is possible. The usage of
      pharmacological stress agents (dobutamine, arbutamine, dipyridamole, adenosine)
      or electrical stimulating methods (transesophageal, intracardial) allow the
      examination of patients unable to exercise in similar accuracy.

PMID- 10907306
TI  - [Contrast echocardiography].
AB  - The intravenous application of an ultrasound contrast agent induces enhanced
      display of blood in all its pathways. Within cardiology, this principle is mainly
      utilized for signal enhancement of color Doppler and spectral Doppler in order to
      improve quantification of congenital and acquired valvular lesions and also for
      improved endocardial delineation during stress tests and in the evaluation of LV
      function. The new domaine of myocardial perfusion imaging by contrast
      echocardiography, however, needed profound technical developments before
      realization of the clinical potential could even be conceived. These are based on
      the complex reactions of microbubbbles in the acoustic field in order to allow
      the sensitive and bubble specific display of intramyocardial contrast effects.
      The presently available acquisition techniques, second harmonic imaging and
      harmonic power Doppler, demonstrate significant improvements if compared to
      traditional fundamental 2-d echocardiography; however, they are still subjected
      to important limitations. There are many anatomical, physiological, and technical
      reasons for insufficient display of intramyocardial microbubbles, the most
      important one being attenuation. It is hoped that the most recently developed
      imaging modality, pulse inversion technique, allows the necessary diagnostic
      accuracy and reproducibility in myocardial perfusion imaging.

PMID- 10907307
TI  - [New techniques for the quantification of myocardial function: acoustic
      quantification, color kinesis, tissue Doppler and "strain rate imaging"].
AB  - In this article, the authors discuss different semi-quantitative methods for the
      analysis of global and regional myocardial function. Analysis of endocardial
      motion and direct measurements of myocardial velocities are the basic principles.
      The former is a two-dimensional technique which, however, requires good image
      quality and which is influenced by motion artefacts. The latter technique has a
      better signal to noise ratio and offers the opportunity to sufficiently quantify
      diastole. Strain rate imaging is a new and interesting way to display and
      evaluate regional myocardial deformation.

PMID- 10907308
TI  - [3D echocardiography].
AB  - Three-dimensional echocardiography has been realized in two different technical
      approaches: first as reconstruction of previously acquired multiple two
      dimensional cross-sections, and recently as real-time 3D echo. Both approaches
      allow one to measure quantitative parameters of cardiac structures, such as mass
      and volume, with an accuracy far superior to 2D echo and equal to nuclear
      magnetic resonance techniques. However, such measurements are labor and time
      intensive. Other spatially complex cardiac structures such as valves, atrial and
      ventricular septal defects, or dynamic outflow tract obstruction in hypertrophic
      obstructive cardiomyopathy can be assessed adequately in both qualitative and
      quantitative fashion. Furthermore, the advent of real-time 3D echo with its
      ability to gather the full 3D data set within seconds promises to widen the
      potential applications of 3D echo, for example, including stress echo.

PMID- 10907309
TI  - [Transesophageal echocardiography (TEE)].
AB  - Transesophageal echocardiography (TEE) is a complementary technique to
      conventional echocardiography (TTE) and is used in patients in whom TTE reveals
      unsatisfactory image quality. The improved resolution in combination with the
      capability to visualize cardiac structures which are not detectable or poorly
      visualized by TTE has brought TEE into increasing use as a routine technique. TEE
      has been proven to be superior to TTE for various indications, e.g., detection of
      infective vegetations or perivalvular abscesses, evaluation of acute chest pain
      or potential embolic sources, evaluation of prosthetic valve function, evaluation
      of hypotensive or hypoxic patients, intraoperative monitoring of LV function or
      control of surgical results after correction of complex congenital heart disease
      or mitral valve reconstruction. TEE is an semi-invasive technique which can be
      performed in > 95% of patients with only minor discomfort; life threatening
      complications are rare (< 0.1%). TEE is a bed-side and low-cost technique which
      can be rapidly applied in the operation room as well as intensive care unit. TEE
      combines functional and morphological data with a high diagnostic accuracy and
      may be, therefore, an important diagnostic tool also for the next millennium
      despite new developments in alternative imaging techniques such as magnetic
      resonance.

PMID- 10907310
TI  - Hepatitis vaccination in patients with chronic liver diseases.

PMID- 10907311
TI  - Surveillance for hepatocellular carcinoma: compliance and results according to
      the aetiology of cirrhosis in a cohort of 141 patients.
AB  - Surveillance for early detection of hepatocarcinoma (HCC) in patients with
      cirrhosis is widely accepted. In a cohort of 141 patients with cirrhosis
      collected during the year 1995, we conducted a surveillance program by performing
      liver ultrasonography and blood alpha-foetoprotein measurement every 6 months.
      The median follow-up was 34 months. This study addressed to two questions: the
      compliance to the surveillance schedule according to the aetiology of cirrhosis
      and the results in terms of emergence of HCC and outcome. Aetiology of cirrhosis
      was alcohol-induced in 86 (61%), HCV-related in 30 (21%) and from other origins
      in 25 (18%). Compliance to the program schedule was good in patients with HCV
      related cirrhosis (29/30--97%) and patients with cirrhosis of "other origins"
      (20/25--80%) but was poor in patients with alcoholic cirrhosis (45/86--52%). The
      lack of compliance was significantly linked to the failure to achieve alcohol
      abstinence. During follow-up, 6 HCC lesions were observed in 6 male patients with
      median age of 68 years. All 6 HCC were single nodule, less than 4 cm and
      accessible to percutaneous acetic acid injection. Nevertheless, the outcome was
      disappointing, four patients dying 3-15 months later (median: 8 months), two of
      them with extensive HCC. One of the two patients still alive developed extensive
      HCC, 36 months after percutaneous acetic acid injection.

PMID- 10907312
TI  - Definition of Barrett's oesophagus.
AB  - Barrett's oesophagus is the eponym applied to the columnar epithelium-lined lower
      oesophagus. In 1976, Paull et al. described three types of columnar epithelia
      lining the distal oesophagus: a junctional or cardiac-type epithelium, a gastric
      fundic-type epithelium and a distinctive type of intestinal metaplasia referred
      to as specialized columnar epithelium. Even the normal oesophagus can be lined by
      2 cm of columnar epithelium. To avoid the problem of false-positive diagnoses,
      arbitrary criteria for the extent of oesophageal columnar lining necessary to
      include patients in studies of Barrett's oesophagus were established in the early
      1980s. The latter criteria require a circumferential segment of columnar lined
      epithelium of 2 or 3 cm in length. There are, however, a number of technical and
      conceptual problems related to this approach. The traditional definition excludes
      shorter segments and tongues of columnar lined epithelium. Only the specialized
      columnar epithelium defined by intestinal type goblet cells carries an inherent
      risk of malignancy. Therefore, a number of investigators currently define
      Barrett's oesophagus as any amount of columnar mucosa in the lower esophagus that
      has histologic evidence of goblet cells (highlighted in biopsies using the alcian
      blue pH 2.5 stain). Recently, short segments of specialized intestinal metaplasia
      in the distal oesophagus ("short segment Barrett's oesophagus") have attracted
      considerable attention. It has also become clear that intestinal metaplasia can
      occur at a normally located gastro-oesophageal junction. The etiology and
      clinical significance (in terms of possible relationship to the adenocarcinoma of
      the cardia) of this "intestinal metaplasia of the gastric cardia" and its
      potential relationship to Barrett's oesophagus are not yet completely understood.

PMID- 10907313
TI  - Barrett's esophagus: the metaplasia-dysplasia-carcinoma sequence: morphological
      aspects.
AB  - In the gastrointestinal tract, epithelial dysplasia is defined as an "unequivocal
      neoplastic transformation, confined within the boundaries of the basement
      membrane" or "the presence of unequivocally neoplastic cells that replace a
      variable proportion of the normal epithelium". It can be recognized by microscopy
      because of cytological and architectural changes. Reactive changes or equivocal
      changes should thus not be called "dysplasia". As dysplasia is confined within
      the basement membrane, it is a noninvasive neoplastic transformation. In the
      lower esophagus lined by columnar epithelium (Barrett's esophagus) dysplasia is
      classified as negative, indefinite or positive. Positive lesions are subdivided
      into low-grade and high-grade dysplasia according to the severity of the lesions.
      Carcinoma in situ (intraepithelial carcinoma) is included in the category of high
      grade dysplasia. The presence of dysplasia can be recognized on biopsies and on
      cytological preparations. Several techniques have been introduced with the
      purpose to improve the diagnostic yield. These include special stains for the
      assessment of mucin, enzymehistochemistry and immunohistochemistry for tumor
      markers such as CEA and CA 19-9 and molecular techniques. Mucin histochemistry,
      enzymehistochemistry and immunohistochemistry for traditional markers have
      limited practical value. The nuclear presence of abnormal products such as mutant
      p53 can be identified using immunohistochemistry and appropriate antibodies. Flow
      cytometry can identify aneuploid cell populations and Fluorescent In Situ
      Hybridization (FISH) can identify chromosomal gains and losses. These techniques
      provide additional information but they identify other phenomena which do not
      necessarily appear at the same moment as dysplasia during the process of
      carcinogenesis. Application of these techniques can however certainly help to
      support a diagnosis of dysplasia while negative results do not necessarily
      disproof such a diagnosis. The temporal course of the progression of dysplasia
      and the development of carcinoma is not well known and seems to be variable. Low
      grade dysplasia may persist for long periods. A direct progression towards
      carcinoma has been noted although more often an increase in the severity of the
      dysplasia, before the development of carcinoma, was seen during the observation
      period. High-grade dysplasia can also persist for many months, sometimes even
      years without obvious evolution but it can also progress rapidly to carcinoma.

PMID- 10907314
TI  - Genetic versus environmental interactions in the oesophagitis-metaplasia
      dysplasia-adenocarcinoma sequence (MCS) of Barrett's oesophagus.
AB  - The prevalence of Barrett's oesophagus has risen over a short time interval
      implying environmental in addition to genetic aetiological factors. Bile salt
      effects from duodenogastro-reflux are assuming increasing importance with
      deoxycholic and taurodeoxycholic acid being particularly associated with
      Barrett's oesophagus. The cellular biology changes appear to follow a progression
      from initial inflammation and oesophagitis to metaplasia and dysplasia through to
      adenocarcinoma. Mechanisms of restitution include epidermal growth factor
      mediated increases in epithelial thickness. This results in basal stem cells
      becoming superficially placed and exposed further to luminal refluxed bile salts.
      Immature stem cells result which undergo mutation to a metaplastic glandular
      phenotype with intestinal metaplasia. P53 mutation increasingly occurs in
      progression to dysplasia and carcinoma and may confer a survival advantage of
      these cell clones by delaying apoptosis. Cell cycling gene mutations occur with
      accumulation of cells in G2 phase. Disruption of cellular checkpoint mechanisms
      in the mitotic process result in loss of heterozygosity and aneuploidy including
      loss of the Y chromosome. Identical mutations between adjacent areas of dysplasia
      and adenocarcinoma supports clonal expansion as the mechanism of carcinogenesis.
      APC tumour suppressor gene mutations are conserved in synchronous carcinomas in
      Barrett's dysplasia and are associated with beta-catenin accumulation in the
      nucleus and cellular migration with invasion. Cumulative genetic errors result in
      abnormal clones with metastatic or angiogenic potential. When a clone with
      malignant potential occurs adenocarcinoma can result completing the progression
      from inflammation to metaplasia and dysplasia through to adenocarcinoma.

PMID- 10907315
TI  - The value of medical imaging in uncomplicated and complicated Barrett's
      esophagus.
AB  - Barrett's esophagus is an acquired condition characterized by a progressive
      columnar metaplasia of the distal esophagus caused by longstanding
      gastroesophageal reflux and reflux esophagitis. Barrett's esophagus is a
      premalignant condition associated with a significantly increased risk of
      developing esophageal adenocarcinoma. The purpose of this article is to provide
      an overview of the radiologic aspects of Barrett's esophagus and esophageal
      adenocarcinoma. Review of the literature shows that some findings on
      esophagography that are relatively specific for Barrett's esophagus are not
      sensitive, while others that are sensitive have a low specificity. Specific
      radiologic features allowing a confident diagnosis of Barrett's esophagus are a
      high esophageal stricture or ulcer associated with a hiatal hernia and/or
      gastroesophageal reflux. A reticular mucosal pattern is a relatively specific
      sign particularly if located adjacent to a stricture and is highly suggestive of
      Barrett's esophagus. Unfortunately, these findings are only present in a minority
      of cases. More common but nonspecific findings include gastroesophageal reflux,
      hiatal hernia, reflux esophagitis and/or peptic stricture in distal esophagus.
      These findings may also be present in patients with uncomplicated reflux disease.
      Barrett's esophagus carries a risk of malignant change. Early adenocarcinoma may
      appear as a plaque-like lesion or with focal irregularity, nodularity, and
      ulceration of the esophageal wall. Invasive adenocarcinoma may be seen as an
      infiltrating ulcerated mass. The radiologic diagnosis of Barrett's esophagus is
      limited by lack of criteria that are both sensitive and specific. The major value
      of double-contrast esophagography is its ability to classify patients into high
      risk (high stricture, ulcer or reticular pattern), moderate risk (esophagitis
      and/or distal peptic strictures), and low-risk (absence of esophagitis or
      stricture) for Barrett's esophagus determining the relative need for endoscopy
      and biopsy. Endoscopy and biopsy are generally advocated to make a definitive
      diagnosis. Endoscopic ultrasound plays a role in the early detection of invasive
      carcinoma and the staging of proven carcinoma but has no role in the surveillance
      of Barrett's esophagus.

PMID- 10907316
TI  - Endoscopic follow-up of Barrett's esophagus: protocol and implications.
AB  - The purpose of endoscopic surveillance in Barrett's esophagus is to detect
      dysplasia and to diagnose carcinoma in an early, treatable stage. Prospective
      trials that study the efficacy of a surveillance program in reducing mortality
      from esophageal adenocarcinoma are lacking. Retrospective studies have shown a
      significantly better outcome in patients with esophageal cancer that is detected
      during a surveillance program. Obviously, surveillance is only indicated for
      those patients fit enough to undergo esophagectomy if high-grade dysplasia (HGD)
      or malignancy is detected. There is no consensus upon what to do with HGD: some
      recommend esophagectomy when HGD is diagnosed, because an important proportion of
      these patients host an adenocarcinoma; others feel that histological proof of
      malignancy should be established before esophagectomy is proposed. Dysplasia is
      not a uniform process, causing sampling problems. Using a strict biopsy protocol
      is helpful to differentiate HGD from carcinoma, but contradictory results about
      this type of rigorous biopsy protocol have been published. Most groups propose
      four biopsy specimens, in a circular fashion, from every 2 cm of the Barrett
      epithelium, with additional biopsies from any mucosal abnormality. Patients with
      long-segment Barrett's esophagus need endoscopic surveillance, even if they
      underwent antireflux surgery. At this moment there are not enough data to support
      a systematic surveillance of patients with short-segment's Barrett's esophagus.
      The following endoscopic strategy can be proposed. No dysplasia: surveillance
      every 2 years. Low-grade dysplasia: surveillance every year; in these cases it is
      recommended to repeat four-quadrant biopsies at 1 cm interval if numerous
      biopsies reveal dysplasia to detect foci of HGD/cancer. High-grade dysplasia:
      repeat immediately four-quadrant biopsies at 1 cm interval; if HGD is confirmed
      esophagectomy is advised to a patient with acceptable operative risk. Ablation
      therapy remains experimental.

PMID- 10907317
TI  - Global HIV epidemic continues to grow.

PMID- 10907319
TI  - Communicable Disease and Public Health readership survey

PMID- 10907318
TI  - Antibiotic prescribing guidance for primary care.

PMID- 10907320
TI  - Treatment on demand: an operational model.
AB  - The goal of "treatment on demand" is to allow all those seeking substance abuse
      treatment immediate entry into a program. Surprisingly, little is understood
      regarding the relationship between the demand for treatment, queues, waiting
      times and treatment admission rates, and treatment capacity. Nor has the increase
      in treatment capacity required to eliminate drug treatment queues, along with the
      expected benefits and costs of such an expansion, been studied carefully. In this
      paper, we present a mathematical model of drug treatment flows for systems where
      the demand for treatment greatly exceeds available supply. The model produces
      estimates of queue lengths, waiting times and treatment admission probabilities
      for any given treatment capacity, and suggests the capacity needed to achieve
      treatment on demand. The model also enables one to contrast the likely costs and
      benefits of changes in treatment capacity. We illustrate the model using San
      Francisco as a case study.

PMID- 10907322
TI  - A mathematical programming approach for scheduling physicians in the emergency
      room.
AB  - Preparing a schedule for physicians in the emergency room is a complex task,
      which requires taking into account a large number of (often conflicting) rules,
      related to various aspects: limits on the number of consecutive shifts or weekly
      hours, special rules for night shifts and weekends, seniority rules, vacation
      periods, individual preferences,... In this paper, we present a mathematical
      programming approach to facilitate this task. The approach models the situation
      in a major hospital of the Montreal region (approximately 20 physicians are
      members of the working staff). We show that the approach can significantly reduce
      the time and the effort required to construct a six-month schedule. A human
      expert, member of the working staff, typically requires a whole dedicated week to
      perform this task, with the help of a spreadsheet. With our approach, a schedule
      can be completed in less than one day. Our approach also generates better
      schedules than those produced by the expert, because it can take into account
      simultaneously more rules than any human expert can do.

PMID- 10907321
TI  - Determining cost savings from attempted cephalic version in an inner city
      delivering population.
AB  - The use of external cephalic version (ECV) is increasingly seen as an important
      clinical management strategy for breech presentation infants. Currently, 75% of
      women with breech presentation at term undergo Cesarean delivery risking adverse
      outcomes and incurring higher costs. ECV, if successful, reduces the rate of
      breech presentation at delivery and the need for Cesarean delivery. Data from an
      inner-city population of delivering women were examined to determine the
      effectiveness of ECV among these minority, low income women. Hospital clinical
      and Medicaid claims data for 679 deliveries with breech presentation were
      studied. Decision tree analysis indicated ECV was successful for 48% of those
      attempted. Based on amounts billed Medicaid, attempting ECV reduced the use of
      resources by a little over $3,000 per delivery. Sensitivity analysis showed,
      however, that the savings may be as low as $906. Multivariate analysis confirmed
      the independent effect of attempting ECV on the probability of Cesarean delivery.

PMID- 10907323
TI  - Simulation of robotic courier deliveries in hospital distribution services.
AB  - Flexible automation in the form of robotic couriers holds the potential for
      decreasing operating costs while improving delivery performance in hospital
      delivery systems. This paper discusses the use of simulation modeling to analyze
      the costs, benefits, and performance tradeoffs related to the installation and
      use of a fleet of robotic couriers within hospital facilities. The results of
      this study enable a better understanding of the delivery and transportation
      requirements of hospitals. Specifically, we examine how a fleet of robotic
      couriers can meet the performance requirements of the system while maintaining
      cost efficiency. We show that for clinical laboratory and pharmaceutical
      deliveries a fleet of six robotic couriers can achieve significant performance
      gains in terms of turn-around time and delivery variability over the current
      system of three human couriers per shift or 13 FTEs. Specifically, the simulation
      results indicate that using robotic couriers to perform both clinical laboratory
      and pharmaceutical deliveries would result in a 34% decrease in turn-around time,
      and a 38% decrease in delivery variability. In addition, a break-even analysis
      indicated that a positive net present value occurs if nine or more FTEs are
      eliminated with a resulting ROI of 12%. This analysis demonstrates that
      simulation can be a valuable tool for examining health care distribution services
      and indicates that a robotic courier system may yield significant benefits over a
      traditional courier system in this application.

PMID- 10907324
TI  - What kind of patients and physicians value direct-to-consumer advertising of
      prescription drugs.
AB  - Direct-to-consumer (DTC) advertising of prescription drugs can enhance the
      physician-patient relationship, as well as benefiting its sponsor. However,
      overall benefits can only occur if the patients value the information enough to
      discuss it with their physicians and the physicians are not predisposed against
      the DTC information. We investigate the impact of demographics and exposure to
      marketing on consumers' and physicians' receptiveness to DTC advertising of
      prescription drugs, using data from two nationwide surveys. We find that
      consumers who have an ongoing need for health care, that is, those with children
      or with a chronic condition requiring medication, value prescription drug
      advertising more highly, while older consumers, consumers who have been sick
      recently, or more educated consumers are more likely to trust their physicians
      instead. We find that more experienced physicians, physicians who see more
      patients, or those who have more exposure to pharmaceutical advertisements are
      more accepting of DTC advertising of prescription drugs.

PMID- 10907325
TI  - The impact of operations competitive priorities on hospital performance.
AB  - A notable lack of empirical analysis exists on hospital operations strategy in
      spite of widespread debate on quality, cost, and service delivery-issues which
      are widely included within the realm of operations competitive priorities. We
      empirically examine the degree of emphasis placed by administrators on
      competitive priorities and what impact this might have on performance of not-for
      profit, general hospitals. Performance is defined as a composite of financial and
      operational performance. Our research shows that management's emphasis of cost
      containment and service delivery consistently results in superior business
      performance. Quality programs are found to be the most preferred competitive
      priority initiative, yet show relatively low relation with performance. This
      suggests that quality programs are a necessary, though not sufficient, component
      of hospital operations strategy. The competitive dimension of flexibility is
      being employed, but on a less universal scale. We conclude that administrators
      are not yet sufficiently skilled in the flexibility priority to make this
      dimension consistently result in superior business performance.

PMID- 10907326
TI  - The relationship between market orientation and performance in the hospital
      industry: a structural equations modeling approach.
AB  - There is general consensus in the research literature that market orientation is
      related to organizational performance. This study examines this relationship in
      the hospital industry. One unique feature of this study is that both market
      orientation and performance are conceptualized as being multi-dimensional
      constructs. Hence the technique of Structural Equations Modeling (SEM) is used to
      examine the relationship. Analyses were based on market orientation and
      performance data obtained from 175 hospitals in a five-state region of the United
      States. The SEM results confirm the multi-dimensional nature of both market
      orientation and performance, and the strong relationship between the constructs.
      Interestingly, this relationship is found to be much stronger for smaller
      hospitals than for larger hospitals. Implications for the hospital industry are
      discussed.

PMID- 10907327
TI  - Where efficiency saves lives: a linear programme for the optimal allocation of
      health care resources in developing countries.
AB  - Morbidity and mortality are directly influenced by the available health care
      budget. In addition, the optimal allocation of this scarce resource to the
      different strata of the health care system depends on the health care priorities.
      This paper presents a linear programming model in order to analyse the impact of
      changes of the health care budget and the goal system of the health care system
      on the optimal allocation to preventive and curative medicine. The model
      demonstrates that the current resource allocation in developing countries is
      inefficient. This calls for a new emphasis on preventive medicine and primary
      care in the political processes in developing countries.

PMID- 10907328
TI  - Midwives helping mothers to breastfeed: food for thought and action.

PMID- 10907329
TI  - Evidence-based care and the breastfeeding couple: key concerns.
AB  - Optimal health care is based on evidence that a) no harm is done when that care
      is provided and that b) the care provided assists in the prevention of further
      problems or the resolution of the presenting problem. Too often, care provided to
      lactating mothers and their breastfeeding offspring lacks evidence supportive of
      the techniques used or care provided. This article addresses 10 common hospital
      based practices and reviews documented evidence related to their effect on
      breastfeeding success. Concepts pertaining to the breasts and breastfeeding that
      require incorporation into the educational offerings of current and future health
      care providers are also identified.

PMID- 10907330
TI  - Nipple pain in breastfeeding women: causes, treatment, and prevention strategies.
AB  - This article identifies problems and conditions that contribute to nipple pain
      during lactation and that may lead to early cessation or noninitiation of
      breastfeeding. Signs and symptoms of poor latch-on and positioning, oral
      anomalies, and suckling disorders are reviewed. Diagnosis and treatment of
      infectious agents that may cause nipple pain are presented. Comfort measures for
      sore nipples and current treatment recommendations for nipple wound healing are
      discussed. Suggestions are made for incorporating in-depth breastfeeding content
      into midwifery education programs.

PMID- 10907331
TI  - Supporting the employed breastfeeding mother.
AB  - The number of women in the workforce is continuing to increase and surveys
      suggest that one-fourth of employed women with a child less than 1 year of age
      will be concurrently breastfeeding and working for at least 1 month. Combining
      breastfeeding and employment is a complex process in American society. Women will
      be seeking practical, sound advice on how to be successful in this combination.
      This article offers suggestions for promoting its success, describes the
      preplanning that needs to occur, and provides current lactation recommendations
      and resources. It also offers information about working with employers, the
      importance of a support network, decisions that each family must make, the use of
      breast pumps; milk storage, lactation enhancement including the use of herbs, and
      practical tips for the mother's working day.

PMID- 10907332
TI  - The experience of sexuality during breastfeeding among primiparous women.
AB  - The purpose of this study was to describe various aspects of sexuality for
      primiparous breastfeeding women. The conceptual framework used for the study was
      Bernhard's theory of women's integrated sexuality which describes female
      sexuality as a multidimensional, biopsychosocial phenomenon. The investigators
      used a descriptive design, analyzing data from the 576 primiparous breastfeeding
      women who, as part of a larger study, completed the Breastfeeding and Sexuality
      Tool at the time of complete weaning. The women were from a large, private
      hospital in urban Minnesota. Subjects completed initial questionnaires during the
      postpartum hospitalization. Follow-up data were collected by phone at 1, 3, 6,
      and 12 months postpartum. Those who had not weaned by 12 months were followed
      every 3 months until complete weaning was reported. Overall, women perceived that
      breastfeeding had a slightly negative impact on the physiologic aspects of
      sexuality, but did not greatly affect the woman's sexual relationship with her
      partner. In addition, breastfeeding mothers perceived their partners' attitudes
      towards breastfeeding and sexuality as slightly positive, and did not worry that
      sexual activity would harm their milk supply or their ability to nurse. Overall,
      breastfeeding had a slightly negative impact on sexuality. However, a wide range
      of responses were reported by the women. Health care providers should be familiar
      with the whole range of possible responses to sexuality while breastfeeding in
      order to appropriately counsel women about what is normal and what to expect
      during this time.

PMID- 10907333
TI  - Breastfeeding the high risk infant: implications for midwifery management.
AB  - The mother of a high risk infant is confronted with numerous parenting
      challenges, not the least of which is the decision about how to nourish her
      vulnerable newborn. Successful breastfeeding depends on overcoming obstacles
      posed by infant condition, maternal health, and the neonatal intensive care
      environment. These obstacles include maternal separation from the nursing infant
      during hospitalization, delayed initiation of the expression of breast milk due
      to maternal illness and/or surgery, the inability to suckle her infant or feed on
      demand, and the lack of sufficient maternal follow-up after discharge. This
      article reviews the benefits of providing breast milk to high risk infants,
      problems that may be encountered by mothers of high risk infants, and the
      interventions that may be used by the midwife to facilitate the breastfeeding
      process.

PMID- 10907334
TI  - Breastfeeding duration among low income women.
AB  - Breastfeeding has been identified as a possible deterrent to the development of
      osteoporosis and breast cancer in women. In addition, infants who are breastfed
      exclusively for at least 4 months reportedly have fewer incidence of SIDS, ear
      infection, diarrhea, and allergies. Further, low income women who breastfeed may
      be empowered by the experience. Increasing the frequency and duration of
      breastfeeding is recognized as a national priority, particularly for low income,
      minority women. Yet, recent national data indicate that in 1997, only 16.5% of
      low income mothers breastfed for at least 6 months. Short breastfeeding duration
      in low income women may be due to problems unique to them; thus, consistent and
      comprehensive breastfeeding support should be provided by midwives, nurses,
      lactation consultants, and peer counselors who are skilled in culturally
      sensitive management of lactation within the context of limited financial and
      social resources. This article focuses on the benefits of breastfeeding, and
      factors that may influence its duration. It also explores culturally relevant
      strategies as well as suggested interventions to increase breastfeeding duration
      among low-income women.

PMID- 10907336
TI  - Assessment of breastfeeding knowledge of nurse practitioners and nurse-midwives.
AB  - The purpose of this study was to replicate a national study of physician
      knowledge, experience, and attitudes about breastfeeding. All family, pediatric,
      and women's health care nurse practitioners and nurse-midwives in a northwestern
      state were surveyed using a mail questionnaire; the response rate was 60.4%.
      Respondents were nearly unanimous in believing that "breast is best" and in
      recommending breastfeeding to expectant mothers as a part of their role. In
      general, 70% of respondents considered themselves effective or very effective in
      meeting the needs of breastfeeding patients. Although respondents were very
      supportive of breastfeeding, they were less knowledgeable about specific
      management strategies. There were differences in attitudes among nursing
      specialties and with years of experience. Overall, this statewide sample of nurse
      practitioners and nurse-midwives had a better understanding of the benefits of
      breastfeeding and an increased sense of effectiveness in managing breastfeeding
      problems than the physician participants in the national study. A national sample
      of nurse practitioners and nurse-midwives is needed to verify and expand on the
      results from this single jurisdiction, where 40% of the respondents were
      graduates of the home institution of the co-investigators.

PMID- 10907335
TI  - Against the odds: breastfeeding experiences of low income mothers.
AB  - This qualitative study asked low income mothers about their experiences of
      breastfeeding care in the health system and about integrating breastfeeding into
      their daily lives. Focus group interviews were conducted with urban and rural
      nursing mothers who participated in the WIC Program and were supported by
      breastfeeding peer counselors. Mothers said that helpful breastfeeding care
      providers knew correct information, established supportive personal
      relationships, referred women to breastfeeding specialists for problems, showed
      enthusiasm for nursing, and facilitated breastfeeding through concrete actions
      during the prenatal, intrapartum, and postpartum periods. Unhelpful providers
      missed opportunities to discuss breastfeeding, gave misinformation, encouraged
      formula supplementation, provided perfunctory or routine breastfeeding care, and
      were hard to contact when problems arose. Women valued their breastfeeding peer
      counselors for responding promptly to distress calls, making home visits, being
      knowledgeable about breastfeeding, providing hands-on assistance, and acting
      personal and caring. Incorporating breastfeeding into daily activities was a
      challenge for many mothers. Ambivalence about the physical bond of nursing,
      personal modesty, and getting on with life at home, work, or school were
      identified as important issues. Listening to the thoughts and experiences of low
      income nursing mothers can help health workers to provide more culturally
      sensitive, effective breastfeeding care to this population.

PMID- 10907337
TI  - Breastfeeding: how could it be enhanced? The perceptions of Vietnamese women in
      Sydney, Australia.
AB  - In Australia, the prevalence and duration of breastfeeding is on the decline. The
      low incidence of breastfeeding includes the immigrant Vietnamese. The purpose of
      this study was to examine Vietnamese women's perceptions of factors that might
      influence their choice of infant feeding and how breastfeeding could be promoted
      and maintained by nurses, midwives, other health professionals, and the health
      care system as a whole. A convenience sample of 124 postnatal Vietnamese women
      from community agencies in western and southwestern suburbs of Sydney was
      interviewed. Content analysis showed that factors that affect their choice of
      infant feeding method were language difficulties in communicating with health
      professionals concerning breastfeeding, lack of social support and follow-up
      care, and attitudes of health professionals toward breastfeeding. To promote and
      maintain breastfeeding within the Vietnamese community in Sydney, Australia,
      appropriate health care planning and implementation based on their social,
      cultural, and language backgrounds and practices need to be considered.

PMID- 10907338
TI  - Breastfeeding links.

PMID- 10907339
TI  - Differentiation of Candida strains by lectin-mediated agglutination kinetics.
AB  - The lectin-mediated agglutination kinetics of Candida albicans, Candida
      tropicalis, Candida glabrata, Candida krusei, Candida kefyr, and Candida
      parapsilosis strains isolated from immunocompromised patients was investigated.
      The rate of the lectin-induced cell agglutination depends on the physiological
      state of the yeast cell population. Therefore, the Candida strains have to be
      cultivated and investigated under identical conditions. Lentil lectin (prepared
      from Lens culinaris), castor lectin, and concanavalin A were used. Different
      yeast species showed different agglutination behaviour. Furthermore, the lectin
      mediated rate of agglutination is a strain-specific property which makes it
      possible to distinguish between different yeast strains of the same species. It
      is concluded that the lectin-mediated agglutination kinetics allows reproducible
      differentiation of yeast strains of the same species.

PMID- 10907340
TI  - Multicentric genetic study of Candida albicans isolates from non-neutropenic
      patients using MLEE typing: population structure and mode of reproduction.
AB  - A mycological survey was conducted on non-neutropenic patients in three distinct
      intensive care units in two hospitals in Marseille (France) from November 1993 to
      November 1995. Candida albicans positive cultures from 62 patients were included
      in this study. Every first isolate of each patient was typed by multilocus enzyme
      electrophoresis (MLEE). The enzyme profiles obtained from 15 polymorphic loci
      were then compared. This analysis demonstrated a strong population
      differentiation of C. albicans infective strains within and between the different
      care units and confirmed the probable preponderant clonal mode of reproduction of
      this yeast.

PMID- 10907341
TI  - Phenotypic variation and antifungal susceptibility patterns of Candida albicans
      strains isolated from neutropenic patients.
AB  - The aim of this study was to investigate the relationship between phenotypes of
      Candida albicans strains isolated from clinical specimens and the susceptibility
      of the strains to three antifungal agents, fluconazole, amphotericin B and
      flucytosine. Oropharyngeal, gastrointestinal and urogenital tract specimens were
      collected from 122 neutropenic patients who had received no previous prophylactic
      treatment. Each of 122 C. albicans strains recovered was found to express one of
      the six phenotypes: smooth, fuzzy, irregular, star, ring and stipple. The mean
      minimum inhibitory concentrations (MICs) of fluconazole was consistently higher
      for C. albicans strains expressing the stipple phenotype. The mean MICs for the
      six phenotypes of C. albicans strains ranged between 1.22 and 7.94 micrograms ml
      1 for fluconazole, 0.99 and 2.55 micrograms ml-1 for amphotericin B and 1.23 and
      1.83 micrograms ml-1 for flucytosine. The antifungal susceptibility of the
      stipple phenotype requires attention, especially in patients who are clinically
      unresponsive to fluconazole chemotherapy or in cases of life-threatening C.
      albicans infections of immunocompromised hosts. Long-term use of fluconazole may
      explain the outcome of the resistant stipple phenotype.

PMID- 10907342
TI  - Itraconazole lung concentrations in haematological patients.
AB  - Itraconazole distribution is largely dependent on its high liposolubility.
      Intrapulmonary lung concentrations remain unknown in haematological patients. We
      report itraconazole lung concentrations in such patients treated with
      itraconazole. Itraconazole and hydroxyitraconazole were measured by high
      performance liquid chromatography in concomitant blood samples and lung post
      mortem biopsies (three cases) or lung lobectomy (one case). These itraconazole
      and metabolite lung concentrations were sufficient to be active on Aspergillus.

PMID- 10907343
TI  - Bifonazole (Mycospor cream) in the treatment of moccasin-type tinea pedis.
      Comparison between combination therapy of bifonazole cream + 10% urea ointment
      (Urepearl) and occlusive dressing therapy with the same agents.
AB  - Moccasin-type tinea pedis(MTTP) is a hardly curable superficial dermatomycosis
      primarily characterized by hyperkeratosis of the sole. In this study, we compared
      the usefulness of combination therapy of bifonazole (Mycospor cream) + 10% urea
      ointment (Urepearl) (overlapping application group = group I) with occlusive
      dressing therapy with the same agents (group II) in the treatment of MTTP, and
      obtained the following results. (1) The clinical improvement rate (percentage of
      "marked improvement" and "moderate improvement") was 60.4% in group I and 83.3%
      in group II. (2) The mycological eradication rate was 48.7% in group I and 82.1%
      in group II after 4 weeks of treatment and 90.9 and 96.9%, after 12 weeks of
      treatment, respectively. (3) The clinical utility rate (percentage of "very
      beneficial" and "beneficial") was 83.3% in group I and 93.8% in group II. These
      results indicate the superiority of both combination therapy of bifonazole + 10%
      urea ointment (overlapping application group) and occlusive dressing therapy with
      the same agents in terms of efficacy and safety for the treatment of MTTP, and
      suggest that they can be recommended for treatment of patients for whom it is
      difficult to use oral antimycotic agents or for patients who fail to respond to
      oral medications alone.

PMID- 10907344
TI  - Effect of serum concentration on Candida biofilm formation on acrylic surfaces.
AB  - The biofilm formation of the oral fungal pathogen Candida on denture acrylic
      strips coated with saliva, serum and, saliva-serum pellicle were examined in
      vitro using Candida albicans (four isolates), Candida glabrata (three isolates)
      and Candida tropicalis (three isolates). The degree of biofilm activity varied
      depending upon both the isolate and the pellicle. Significantly increased biofilm
      activity on the pellicle (particularly serum)-coated strips was observed with
      three isolates of C. albicans and another of C. glabrata on protein-coated
      acrylics, with increasing concentration of serum in the pellicle. Similar trends
      were observed with one isolate of C. albicans and C. glabrata, although the
      effects of pellicles were not significant. In contrast, with all three isolates
      of C. tropicalis and a single isolate of C. glabrata, although the biofilm
      activity on the protein-free control strips was significantly higher than that of
      saliva-coated strips, the increase in activity of pellicle-admixed biofilm
      depended upon the serum concentration. Candidal biofilm formation on acrylic
      surfaces is essentially promoted with increasing concentration of serum in the
      pellicle. This suggests that inflammation in the oral environment would
      facilitate fungal colonization on denture acrylic.

PMID- 10907345
TI  - Funguria and Candida-specific immunoglobulins in patients with systemic
      candidosis.
AB  - Funguria, indirect anti-Candida haemagglutination test (C-IHT) and Candida
      specific immunoglobulins C-IgM, C-IgG and C-IgA were investigated under suspicion
      of systemic candidosis in critically ill patients. A total of 143 urine cultures
      were studied for Candida from 74 adults and a median count of log 3.0 CFU ml-1
      was found. Most isolated Candida species were Candida albicans and Candida
      glabrata. In 14 cases of candidaemia there was no regular agreement between the
      finding of Candida species in blood and urine. In cases with candiduria > = or
      log 3.0 CFU ml-1 a stronger increase of C-IHT titres and all three Candida
      specific immunoglobulins after 5-7 days was observed. Some statistically
      significant correlations were found between the levels of urinary yeast counts
      and immunological parameters concerning C-IHT, C-IgA and C-IgG on the first day
      and after 5-7 days. Clinical findings in some cases coincided well with funguria
      and courses of titres before and after treatment. CONCLUSION: In critically ill
      patients suspected of having systemic candidosis not only blood cultures should
      be made. Cultural studies with specimens taken from different sites including
      funguria are essential for a complete specific serological investigation.

PMID- 10907346
TI  - Case report. Primary cutaneous histoplasmosis in an immunosuppressed patient.
AB  - A case of cutaneous histoplasmosis is reported in an 80-year-old man with
      rheumatoid arthritis who had been treated with steroid therapy for 15 years. The
      patient developed a large ulcerative lesion on the back of the left hand and on
      the distal third of the left dorsal forearm after a slight trauma. Diagnosis was
      based on histological and mycological examination. Systemic involvement was not
      found. The lesions healed after 2 months of therapy with 100 mg day-1
      fluconazole, confirmed at follow-up 1 year later.

PMID- 10907347
TI  - [Calcium receptor (CaR): a new approach to regulation of calcium homeostasis].
AB  - In recent years the receptor sensing calcium (CaR) has been discovered on the
      surface of parathyroid cells and some other organs cells which revised our
      understanding of mechanisms involved in regulation of body calcium balance. It
      was shown that stimulation of CaR induced by an increase of extracellular ionized
      calcium concentration resulted in an increase of intracellular calcium and
      subsequent decrease of parathyroid hormone (PTH) secretion from parathyroid
      cells. Calcium receptor was also discovered in nephron segments reabsorbing
      calcium which allowed to understand the mechanisms underlying some inherited
      disturbances of calcium balance regulation i.e. in familial hypocalciuric
      hypercalcemia or hypercalciuric hypocalcemia. Investigations on CaR structure
      revealed the mutations in those inherited syndromes leading to increase or
      decrease of parathyroid and nephron cells receptor sensitivity to calcium. The
      description of the receptor properties resulted in development of a new group of
      compounds called calcimimetics which are more efficient than calcium itself in
      stimulation of CaR and subsequent decrease of PTH secretion. Calcimimetics in
      perspective might have a therapeutic application. Under investigation is
      synthesis of calcilytics, compounds which through an interaction with CaR result
      in increase of PTH secretion potentially leading to a clinical application.

PMID- 10907348
TI  - [Clinical observation of osteoporosis in adolescents].
AB  - The aim of the study was to evaluate the occurrence of clinical and biochemical
      symptoms of osteoporosis in 15 children aged from 10 to 18 years. In this group
      were 7 children with idiopathic juvenile osteoporosis, 2--with osteogenesis
      imperfecta and 6 children with secondary osteoporosis. The diagnosis of
      osteoporosis was based on the result of densitometric examination. The
      examination was performed with dual-energy X-ray absor-ptiometry (DEXA), with
      modality by Lunar. Anamnesis and clinical symptoms supported by X-ray examination
      of the painful region were used as a standard procedure. Biochemical examinations
      of calcium-phosphorus metabolism included ions and PTH concentrations in blood
      serum, and the activity of bone isoenzyme of AP. Besides, ions excretion and
      total hydroxyproline in 24 hrs collection of urine were assessed. The results of
      our investigations showed that in children with osteoporosis clinical and
      biochemical abnormalities were various. Pain in the lower limbs and weakening of
      muscle strength were the most frequently observed clinical symptoms. Among
      biochemical indices, urine excretion of hydroxyproline and increased
      concentration of isoenzyme of alkaline phosphatase were of the greatest practical
      significance.

PMID- 10907349
TI  - [Selected markers of bone metabolism in boys with constitutional delay of growth
      and puberty].
AB  - The aim of the study was to determine serum concentration and urinary excretion
      of selected parameters of bone metabolism in boys with constitutional delay of
      growth and puberty (CDGP) in the relation to pubertal stages. The study group
      consisted of 41 boys (aged 8 to 18 yrs) with CDGP. Patients were divided on the
      basis of Tanner's criteria into 4 groups according to the pubertal stage. Serum
      alkaline phosphatase (AP) activity and serum osteocalcin (OC) concentration as
      markers of bone growth, as well as urinary deoxypyridinoline (DPD) as a marker of
      bone resorption were determined. Serum AP activity in 31 (75.6%) boys was within
      normal age range. Mean values of serum AP activity increased insignificantly from
      I to IV stage of puberty. Serum OC concentrations were normal in 33 (80.5%)
      patients. Eight (19.5%) boys showed decreased values of serum OC concentration.
      Mean OC concentration insignificantly increased with the pubertal stages. DPD
      urinary excretion was within normal age range in all patients and was the highest
      in stage III of pubertal stage. No significant abnormalities of bone metabolism
      parameters in boys with constitutional delay of growth and puberty were found.

PMID- 10907350
TI  - [Progress in measurement of the calcaneus using ultrasonic methods in children
      and adolescents].
AB  - At present, Dual Energy X-ray Absorptiometry (DEXA) method is a reference method
      to diagnose osteoporosis. This method allows to measure bone density and bone
      mass, however bone quality can not be estimated. Quantitative ultrasound (QUS)
      method provides information about bone structure. The aim of our work was the
      evaluation of QUS method in healthy children, establishing reference values in
      cross-sectional study of healthy children aged 7-18 yrs and to examine the annual
      change of ultrasound parameters in prospective study at pubertal. Group of 530
      girls and 369 boys was recruited from Warsaw schools, and right heel was measured
      with Achilles Plus apparatus. Measurements were repeated after 1 year, in a
      subgroup of 153 children aged 9-13 yrs. The method was adapted for paediatric
      measurements by using limiter of ultrasonic wave and pads for positioning foot in
      water chamber. Speed of sound (SOS) and broadband ultrasound attenuation (BUA)
      were measured and Stiffness index was calculated. Width of heel, at the same
      location as QUS measurement, was also measured using calipers. SOS, BUA and
      Stiffness values increased by age in boys and girls. BUA and Stiffness values
      were significantly higher in 15, 16 and 17 year old boys than in age-matched
      girls (in 18 yrs--only Stiffness). However, there were no significant sex
      differences in annual increase of SOS, BUA and Stiffness, although the biggest
      increase was observed between the age of 13-14 yrs for boys and 11-12 yrs for
      girls. That may reflect pubertal spurt of body growth but that relationship was
      not confirmed by annual increases calculated from cross-sectional data.
      Statistically significant correlation of SOS, BUA and Stiffness with body mass,
      height, body mass index (BMI) and heel width was observed. Normalization of SOS,
      BUA and Stiffness on heel width decreased force of that correlation but it was
      still statistically significant. Dynamics of SOS, BUA and Stiffness increase by
      age was higher in boys than in girls. This phenomenon is probably related to
      higher peak bone mass in men than in women, and lower risk of fracture in men,
      especially concerning hip. Increase of speed of sound, broadband ultrasound
      attenuation and stiffness index by age, and their correlations with body mass,
      height and body mass index reflects bone growth in children and adolescents.
      Broadband ultrasound attenuation and Stiffness index show sex differences in bone
      development in adolescence. Higher dynamics of the increase of speed of sound,
      broadband ultrasound attenuation and Stiffness index by age in boys confirms
      faster bone mass accumulation in boys than in girls.

PMID- 10907351
TI  - [Quantitative ultrasound densitometry (QUS) and dual X-ray densitometry (DXA) in
      patients with rheumatoid arthritis].
AB  - The aim of this study was to assess of bone mineral content (BMC) and bone
      mineral density (BMD) of the forearm using DXA technique (DTX-200) and to
      evaluate broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the
      heel using QUS technique (DTU-ONE). We examined 83 RA patients: 73 women and 10
      men, at average age (55.0 +/- 12.2 yrs), ranging from 29 to 85 yrs. Average
      disease duration was 112.6 +/- 98.1 months. Disease activity was assessed
      according to Mallya and Mace index and radiological stage of the disease
      according to Steinbrocker index. We found significant correlation between BMC,
      BMD and BUA (r = 0.6572, r = 0.6081, respectively) and between BMC, BMD and SOS
      (r = 0.4704, r = 0.4723, respectively). IN CONCLUSION: quantitative ultrasound
      parameters (BUA and SOS) significant correlate with BMC and BMD values of the
      forearm assessed by DXA technique in rheumatoid arthritis patients.

PMID- 10907352
TI  - [Incidence of osteoporosis in patients with rheumatoid arthritis].
AB  - Juxta-articular osteoporosis in rheumatoid arthritis (RA) is an early and
      specific pathology in this disease, however in RA patients there are also factors
      predisposing for the development of the generalised bone atrophy. 103 female
      patients with the diagnosis of RA established according to ACR criteria were
      included in the study. Its aim was to evaluate the generalised osteoporosis
      incidence in women suffering from RA as well as to find out how osteoporosis was
      related to certain clinical symptoms and laboratory findings, the disease process
      activity, and the treatment used. The mean age of the patients was 57.6 +/- 12
      years, and the disease duration was 11.4 +/- 9 years. The bone mineral density
      (BMD) was measured by DEXA method with a LUNAR device and included: the radial
      bone in its 1/3 of the shaft's distal part; L1-L4 vertebral region; and the
      proximal part of the femoral bone. The division into subgroups was done basing on
      the 1994 WHO criteria. In RA female patients generalised osteoporosis was
      observed more frequently than in the control group. The study discovered a
      negative, statistically significant, correlation between BMD values and: the
      disease duration, the time of joint involvement acc. to Steinbrocker, the degree
      of functional impairment, the presence of extra-articular lesions, periods of
      immobilisation. There was also a dependence found upon the presence of positive
      Waaler-Rose reaction, and upon the therapy with Methotrexate and D-penicillamine,
      and when the patients were treated with glicocorticosteroids--upon the cumulative
      dose.

PMID- 10907353
TI  - [Glucocorticosteroid induced osteoporosis in patients with rheumatoid arthritis].
AB  - Glucocorticosteroids have been recognized as a well known risk factor for drug
      induced osteoporosis. Many studies have shown a decrease in bone mass, bone
      quality disorders and an increase in the risk of fractures in patients with long
      term corticosteroid therapy. Rheumatic patients, particular with rheumatoid
      arthritis, who are usually chronic steroid users are at the highest risk. On the
      other hand uncontrolled active inflammatory process is also a main factor for
      rapid bone loss. Some studies suggest that patients with low dose corticosteroid
      therapy (prednisone 5 to 7.5 mg per day) are not at increased risk of
      osteoporosis. Our study of 36 rheumatoid arthritis women treated with daily
      prednisone doses between 5 to 7.5 mg in comparison with non-steroid control group
      confirmed the above suggestion.

PMID- 10907354
TI  - [Treatment program for osteoporotic fractures].
AB  - The Department of Orthopedics and Traumatology in Siedlce was responsible for
      specialized care of 662,000 people of the Siedleckie region in 1997. In the
      period from 01.01.97 to 31.12.97, 280 osteoporotic fractures of proximal femur,
      vertebral bodies and distal radius were treated in patients over 50 years of age.
      High impact trauma cases were excluded as well as those involving different than
      osteoporotic pathology of bone. The majority (217) of the fractures referred to
      the proximal femur (trochanter--125, neck--92). In these cases, operational
      methods (183) were used: Ender intramedullary nailing (108), hemialloplastics
      (56), hip screws (19). There were 39 patients hospitalized with the distal radius
      fracture, 29 of them were operated. The fractures of the vertebral bodies (24)
      were stabilized with Jewett brace (21). The results of osteoporotic fracture
      treatment in the Department support validity of principles of early operational
      treatment and intensive pre- and postoperative rehabilitation.

PMID- 10907355
TI  - [Economic aspect of osteoporotic fracture treatment].
AB  - The authors analyzed 307 cases of osteoporotic fractures of proximal femur,
      distal radius and vertebral bodies treated in the Department of Orthopedics and
      Traumatology in Siedlce in 1997. The majority (243) of the fractures referred to
      the proximal femur. They were treated operatively (202) by Ender intramedullary
      nailing, hemialloplastics or fixation with hip screws. There were 40 patients
      hospitalized with the distal radius fracture, 29 of them were operated. The
      fractures of the vertebral bodies (24) were stabilized with Jewett brace or
      plaster jacket. When analyzing costs of hospital treatment of osteoporotic
      fractures, the authors considered the number of patients, the period of hospital
      stay and the number and type of surgeries. Higher costs of the therapy of
      osteoporotic fractures in comparison with the treatment of other cases in the
      orthopedic-traumatic ward were proven.

PMID- 10907356
TI  - [Effects of amsacrine and cytarabine on bones in rats].
AB  - Development of neoplastic diseases can lead to various metabolic changes in the
      bone tissue. The aim of the present study was to investigate effects of two
      antineoplastic agents: amsacrine and cytarabine on the bone system in rats. The
      experiments were carried out on male Wistar rats (initial body mass: 115-150 g).
      Amsacrine or cytarabine were administered subcutaneously in a dose of 3 mg/kg
      daily for four weeks. Cytarabine was administered every day, whereas amsacrine
      was administered every day for the first 7 days and then, after a five-day break,
      every second day up to the end of the experiment. The results were compared with
      those of appropriate control groups. Bone mass, length, diameter, mineral and
      calcium content, incorporation and release of 45Ca+2 in bones, transverse growth,
      width of endosteal and periosteal osteoid, transverse cross-section area of the
      cortical part of the diaphysis and of the marrow cavity in the tibia, width of
      epiphyseal cartilage, width of trabeculae and mechanical properties in the femur
      were examined. Administration of amsacrine caused osteopenic changes in rat
      bones, with decreases in bone mass, mineral content, longitudinal and transverse
      growth of the long bones, width of endosteal and periosteal osteoid, transverse
      cross-section area of the cortical part of the tibial diaphysis, width of
      trabeculae and width of epiphyseal cartilage. Disorders in the calcium metabolism
      in the bone tissue (decreases in the incorporation and release of 45Ca+2 in
      bones) and worsening of mechanical properties of the long bones were observed.
      After administration of cytarabine, the damages to processes of bone tissue
      remodeling were much lesser. Decreases in bone mass, bone mineral content and
      incorporation and release of 45Ca+2 were observed.

PMID- 10907357
TI  - [Osteoporosis in children].
AB  - Osteoporosis is defined as a bone disorder with low bone mass and altered bone
      quality leading to fractures. In adult patients as a reference point for its
      diagnosis peak bone mass reached in second decade of life is utilized. In
      children the mean values of age matched control group are used as a reference
      point for diagnosis of osteoporosis. As a critical value two standard deviations
      below the reference values of the control group in children are used.
      Interpretation of the densitometric measurements in children is more complicated
      than in adults because of heterogeneity of the skeleton and continuous growth of
      children. Obtained results are affected by age, sex, body mass, height, bone age,
      environmental factors and illnesses. Osteoporosis in children is observed primary
      symptom in osteogenesis imperfecta and idiopathic juvenile osteoporosis.

PMID- 10907358
TI  - [Hypophosphatemic rickets].
AB  - Familiar hypophosphatemic rickets (X-linked hypophosphataemia) occurs very
      rarely, nevertheless it makes a significant medical problem because of the fact
      that misdiagnosed or late diagnosed leads to physical development retardation and
      to severe deformities of extremities. In the case of severe deformities the
      surgical treatment is needed. We present the case of the 5 year old girl with X
      linked hypophosphataemia, who was late diagnosed, in spite of appearance of
      typical clinical symptoms (short stature and deformities of extremities) and
      typical laboratory findings (severe hypophosphataemia, serum calcium levels at
      the lower normal range). This girl had been "observed" (by a family doctor) for 3
      years because of "varus deformity of legs". Despite considerably abnormal
      developmental parameters: height and weight << 3rd percentile (height >-3 s.d.
      for age), length of lower limbs >-3 s.d. for age and abnormalities in X-ray
      images of lower limbs (at the age of 3 5/12 presence of diaphysial deformations
      and abnormal metaphyses with zones of inadequate mineralization) the girl had not
      been diagnosed. After the admission to The Department of Pediatrics,
      Endocrinology and Disease of Adolescents: TRP 69.1%, PO4- 0.7-0.78 mmol/l, Ca
      2.24-2.25 mmol/l, Mg 0.78 mmol/l, normal serum level of 25(OH)D (15.4 ng/ml [n.
      11-54]), reduced serum level of 1 alpha 25(OH)2D (5.2 pg/ml [n. 15-70]), PTH 56
      pg/ml [n. 10-70], ALP 401 U/l, ACP 9.5 U/l. 24-hour urine: PO4- 0.36-0.60 mmol/kg
      b.w., Ca 0.021 mmol/kg b.w. Probably, the girl will need surgical treatment
      because of severe bone deformities.

PMID- 10907359
TI  - [Multifocal osteolysis as a result of delayed diagnosis for primary
      hyperparathyroidism].
AB  - Primary hyperparathyroidism caused by solitary adenomas occurs rarely (especially
      in children and adolescents). The clinical manifestations are usually subtle and
      that is why the mentioned disorder is usually late diagnosed and as an effect-
      late treated. We present the case of a 17 year old girl, an ambulatory patient
      who had been "observed" for over 12 months because of persistent ostealgia. She
      had not been properly diagnosed. The first diagnostic investigation of calcium
      and phosphate balance was provided only when multifocal osteolysis of tibias, hip
      and metacarpal bones was detected and biopsy of the mentioned osteolytic lesions
      was done. After the admission to The Department of Pediatrics, Endocrinology and
      Disease of Adolescents: Ca 3.02-3.06 mmol/l, PO4- 0.32-0.62 mmol/l, ACP 19.4 U/l,
      ALP 864 U/l, PTH 770 pg/ml [normal values: 10-70]. Densitometry findings: BMD
      (Neck[L]) 0.636 g/cm2, BMD (Neck[R]) 0.722 g/cm2. The parathyroid adenoma was
      removed after the exploration and localization with MIBI99mTc (scintigraphy).
      Clinical diagnosis was verified by histologic findings. 5 months after: BMD
      (Neck[L]) 0.850 g/cm2, BMD (Neck[R]) 0.741 g/cm2, calcemia 2.38 mmol/l,
      phosphatemia 1.14 mmol/l, ACP 6.2 U/l, ALP 159 U/l. Radiograms show evident
      improvement of bone tissue structure.

PMID- 10907360
TI  - [Drugs stimulating insulin release. Importance of their use for improving
      glycemia, safety and quality of life in diabetes mellitus type 2].
AB  - Etiopathogenesis of diabetes mellitus is bipolar. On one hand there occurs
      impairment in beta-cell function caused by genetic factors or abnormal
      development during fetal period. On the other hand defects of peripheral insulin
      action are also of significant importance. The bipolarity is also expressed by
      changing relationship between genetic and environmental factors. Insulin release
      is connected with closing ATP-dependent kalium channel, a structure closely
      connected with sulfonylurea receptors. Several receptors may be distinguished:
      SUR1 in Langerhans isles and SUR2 in heart (SUR2A) and vessel smoot muscles
      (SUR2B). In the treatment of insulin release disorders sulfonylureas are still of
      significant importance though repaglinid and phenyloalanine derivates also have
      some clinical importance. Within sulfonylurea derivates there have been developed
      some preparations of slow drug release (Glibenese GITS, Diaprel MR). One daily
      dose of Glibenese GITS and lower tendency to hypoglycaemia favour acceptation of
      the therapy by the patients what is also important for their quality of life.
      Quality of life is now regarded as important as obtaining good indices of
      diabetes control.

PMID- 10907361
TI  - [QT dispersion in patients treated with repeated percutaneous transluminal
      coronary revascularization].
AB  - In this study the group of 30 patients with coronary artery disease (mean age 55
      +/- 7 years) were examined. All patients underwent repeated percutaneous
      transluminal coronary revascularisation (rePTCR) due to coronary artery
      restenosis after primary coronary angioplasty. QT dispersion (dQT) and the
      corrected QT dispersion (dQTc), obtained applying Bazett's (dQTB) and Hodge's
      (dQTH) formulas, were measured before rePTCR and 7 days after rePTCR. Standard 12
      lead electrocardiograms, 25 mm/s speed, were used. QT dispersion, defined as a
      difference between maximal and minimal QT intervals, was manually measured. The
      significant decrease of dQT after rePTCA was observed. Mean dQT before rePTCR was
      88.67 +/- 29.09 ms and 64.00 +/- 28.96 ms after rePTCR (p < 0.0001). The changes
      of dQTc (dQTB, dQTH) were similar. Mean values of dQTB before and after rePTCR
      were 92.97 +/- 34.40 ms and 65.42 +/- 29.80 ms respectively, and mean values of
      dQTH were 94.90 ms +/- 37.31 ms and 70.98 ms +/- 32.85 ms. It was also noted that
      the frequency of appearance of dQT exceeding 80 ms significantly decreased after
      rePTCR (dQT exceeded 80 ms in 17 cases before rePTCR vs 5 cases after
      revascularisation). Increased QT dispersion can be a marker of the coronary
      artery restenosis.

PMID- 10907362
TI  - [A test for evaluating specificity and course of tilt table testing based on two
      groups of healthy volunteers (adolescent athletic swimmers and controls)].
AB  - The aim of this study was to estimate the results of tilt table testing in two
      groups of healthy adolescents--swimmers and control. Cardio-vascular reactions on
      tilting were determined by the measurements of heart rate (HR), systolic (SBP)
      and diastolic blood pressure (DBP). The study was carried out in accordance with
      the Polish Cardiac Society procedure. The positive tilt table testing results
      were observed in most young swimmers and in about thirty per cent of controls.
      The differences in the cardiovascular reactions were observed, too. The clinical
      interpretation and usefulness of these results must be established by future
      investigations.

PMID- 10907363
TI  - [Circadian rhythm of autonomic heart activity in patients with primary essential
      hypertension treated with angiotensin converting enzyme inhibitor].
AB  - Although the immediate effects of angiotensin converting enzyme inhibitors (ACEI)
      on cardiac autonomic innervation have been extensively studied, little is known
      about circadian rhythm of heart rate variability (HRV) in these patients. The
      purpose of the present study was to investigate circadian changes of the
      autonomic activity in patients with essential hypertension treated with ACEI,
      which may play some role in the pathogenesis of hypertension. We studied 10
      middle age patients with essential hypertension (treated with ACEI--enarenal at
      least 1 yr.) and 10 age, gender matched control subjects. Heart rate variability
      (HRV) was calculated from the 24-hr ambulatory electrocardiograms by the Fourier
      transformation. Power spectra were quantified at 0.003-0.04 Hz--very low
      frequency power (VLF), 0.04-0.15 Hz--low frequency power (LF) and 0.15-0.40 Hz-
      high frequency power (HF). The HF component and the ratio LF to HF were used as
      indices of the parasympathetic activity and balance between sympathetic and
      parasympathetic activities. RESULTS: The circadian rhythms of the LF, HF and
      LF/HF ratio differed significantly. In control group, LF, HF increased but LF/HF
      decreased (p < 0.05) at night, in hypertensive patients LF, HF increase was
      attenuated at night but LF/HF increased (p < 0.05). In control subjects when
      compared to hypertensive patients power spectrum HF was doubled at night.
      CONCLUSION: These findings suggest that in hypertension primary cardiac autonomic
      dysfunction might contribute to altered circadian rhythm leading to the
      development of cardiovascular diseases despite long term normalisation of high
      blood pressure.

PMID- 10907364
TI  - [Uprighting test, deep respiration test and Valsalva test in patients with
      diabetes type 1].
AB  - Autonomic diabetic neuropathy of cardiovascular system is one of the late
      diabetic complications. The aim of the study was to compare heart rate time
      domain analysis in 23 healthy controls and in diabetic patients without (N0; n =
      34) and with complications (N1, n = 55) such as retinopathy, peripheral
      neuropathy as well as autonomic neuropathy. The study was performed in a group of
      89 patients with diabetes mellitus type 1. Classical tests of Ewing battery
      (upright test, Valsalva test, deep breathing test) were performed using the
      ProSciCard machine as well as parameters of time domain analysis were observed
      during prolonged to 15 minutes standing in upright body position. Comparing group
      N1 to group N0 significantly higher heart rate, lower standard deviation of RR
      interval as well as lower value of rMSSD both at rest and during prolonged stay
      in upright position were demonstrated.

PMID- 10907365
TI  - [Investigation of prostaglandins in supernatant of cultured monocytes].
AB  - Monocytes, mononuclear white cells play an important role in the immunological,
      inflammatory and in the haemostasis system. The aim of our study was the complex
      assessment of the ability of monocytes to release selected prostaglandins in the
      fluid cultures stimulated and nonstimulated by a lipopolysaccharide E. coli
      (LPS). Monocytes were isolated from the whole blood according to the method of
      Boyum. The monocytes cultures were raised in the fluid environment, on the base
      of RPMI 1640 supplemented with autologous serum. We showed that thromboxan A2 was
      the main metabolite of the arachidonic acid released by monocytes on the
      cyclooxygenase pathway. The rest of the prostaglandins, mainly PGI2 were released
      in very small quantities. Thromboxane B2 release in response to LPS could be a
      mechanism active in disorders such as disseminated intravascular coagulation
      induced by bacterial endotoxins.

PMID- 10907366
TI  - [Phagocytic activity of blood platelets before and after renal artery
      embolization in patients with renal cancer].
AB  - Embolization consists in the occlusion of renal artery and its ramifications,
      which induces acute renal infarction. Renal artery embolization, causing
      necrosis, stimulates cellular reactions within and around the neoplasm. The
      interaction of neoplastic cells with blood platelets is of great importance in
      the development of neoplastic disease. Neoplastic cells exert a stimulatory
      effect on blood platelets. During activation, platelets change in shape and
      secrete certain substances. We conducted this study measuring the phagocytic
      activity of blood platelets. 45 patients suffering from renal cancer were
      examined (22 women and 23 men) before and after embolization. Diagnosis was
      established basing on the patients' history, clinical picture, and
      ultrasonographic, urographic and angiographic examinations. The study
      demonstrated that embolization led to an increase in platelet count and decrease
      of phagocytic index.

PMID- 10907367
TI  - [Health-toxicologic aspects of some fungi].
AB  - Recent findings of fungi in food products of such renomed companies as Coca-Cola
      and Danone resulted in society-wide alert in Poland. Humans have contact with
      fungi everywhere. Every food product covered with mould or having marks of it
      should be discarded. We should mention that cutting of or skimming the mould is
      totally ineffective and dangerous, because of the fact that rest of the product
      will contain products of fungal metabolism such as mikotoxins, which are, of
      course, invisible. Modern food producing technologies effected in microorganism
      free products, but sporadically we can find dead fungi debris due to improper
      washing procedures of multi-use bottles, like it was observed in Coca-Cola
      products. As for mould-covered cottage cheese type products of Danone, most
      probably reason was improper handling of ready, sealed products during transport
      and storage. Even minimal physical injuries to air-tight containers resulted in
      sporae penetration to milk products and finally contamination with mikotoxins.

PMID- 10907368
TI  - [Nutritional therapy and the immune system].
AB  - Malnutrition is one of the consequences of chronic and neoplastic diseases.
      Therefore the attention has been paid recently to the most appropriate
      nutritional therapy in order to reduce the number of postoperative complications,
      mortality rates and the length of hospitalisation. Administered nutritional
      substances should cover basic and calorific demands. However it was observed that
      malnutrition leads to the state of immunosuppression. Several studies were
      carried out using potentially immunostimulating substances e.g. nucleotides, some
      of amino acids, vitamins and trace elements or unsaturated fatty acids, in
      addition to the nutritional support. The authors are presenting a review of the
      current state of knowledge and data from clinical trials on the immunostimulating
      role of the nutritional components.

PMID- 10907369
TI  - [Sexual differentiation of the human brain].
AB  - Normal human development requires the compatibility between genetic sex (sex
      chromosomes), sex of gonades (tests or ovaries), genitalia (external and internal
      sex organs), somatic features (body characteristics) and psychic sex. The psychic
      sex, called frequently gender, consist of gender identity (self-estimation),
      gender role (objective estimation) and sexual orientation (hetero- or
      homosexual). It was believed that the psychic gender depends only on socio
      environmental influences such as rearing, learning and individual choice.
      Although, the process of sexual differentiation of human brain is not completely
      elucidated, it has became recently evident that endogenous hormones more then
      socio-environmental factors influence gender differences. Experimental studies on
      animals revealed that transient action of sex steroids during perinatal period of
      life is crucial for the dymorphism of sexual behavior (male or female) in
      adulthood. It seems, that also in the human male neonates testosterone produced
      by testes perinatally takes the main role in the irreversible masculinization of
      the brain i.e. creation of the differences vs. female brain. The evaluation of
      patients with disturbances of sexual differentiation of external genitalia (the
      lack of the testosterone transformation into 5-alpha dihydrotestosterone in
      peripheral tissues of men or the inborn excess of androgens in women with the
      congenital adrenal hyperplasia) has served as a useful clinical model for
      understanding factors, affecting the formation of gender. In these individuals
      the formal sex established according to genetic sex and somatic sex may be
      incompatible with gender identity and role. However, it has been found that the
      female gender identity is most frequently associated with the presence of ovaries
      or the lack of gonads (gonadal dysgenesis), while the male gender identity appear
      most frequently in the presence of testicular tissue irrespective of female or
      hermaphrodite (intersex) phenotype. In genetic men with the absence of male
      genitalia formation, caused by the aberrant function of androgen receptor, the
      gender identity depends on the severity of the disorder: female gender identity
      in the complete androgen insensitivity syndrome and female or male gender
      identity in the complete androgen insensitivity syndrome and female or male in
      the partial androgen insensitivity. These clinical observations confirm the
      experimental data indicating androgen role in the male gender identity creation.
      This knowledge is necessary for the decision of the direction of surgical
      correction of sex organs in children with ambiguous genitalia, which should not
      depend on the expected efficiency to perform sexual intercourse, but mostly on
      the expected or already present individual gender identity.

PMID- 10907370
TI  - [Pseudohypoparathyroidism].
AB  - The article presents data concerning pseudohypoparathyroidism (PH TP). It is an
      unusual disease, which is characterized by the resistance of bones and kidney to
      PTH, followed by hypocalcaemia, hyperphospha-taemia, glandulary hypertrophy and
      hypersecretion of PTH. Patients with PTHT clinically manifest tetany seizures,
      soft tissue calcifications and many congenital malformations. The disease has a
      genetic etiology, it is connected with chromosome X and more often found in
      women. Clinical symptoms may be different and depend on genetic defect or its
      selectivity with reference to the tissues. At present we can distinguish three
      types of PHPT and pseudo-pseudo-HPT. The disease usually appears in the infancy.
      Early diagnosis and vitamin D3 or calcium treatment seem to be the most important
      for patient's condition. Too late treatment threatens with brain calcification
      followed by neurological defects and mental retardation. The long-lasting effect
      of PTH in bones can lead to their destruction, if bone receptors are completely
      sensitive.

PMID- 10907371
TI  - [Genetic predisposition to cardiovascular diseases].
AB  - The development of cardiovascular system disorders depends on both environmental
      and genetic factors. Precise mechanism by which genetic factors may promote
      atherosclerotic lesion formation is still under investigation. From multiple
      candidate genes for cardiovascular disorders the special attention should be paid
      to that which control synthesis of molecules involved in atherosclerosis process.
      For now lots of experiments have been done to test specific genes speculated to
      be crucial for the onset and progression of atherosclerosis, including genes of
      lipoprotein metabolism, coagulation and fibrinolysis system, renin-angiotensin
      system and substances influencing the metabolism of arterial wall. Many of them
      showed the association between tested polymorphisms and pathogenesis of
      cardiovascular diseases.

PMID- 10907372
TI  - [Hemangiopericytoma localized in the peritoneum].
AB  - The authors present a rare case of intraperitoneal haemangiopericytoma.
      Diagnostic and therapeutic procedures were discussed based on current literature.

PMID- 10907373
TI  - [Hemolytic-uremic syndrome in a patient with bacterial food poisoning].
AB  - A rare case of a 47-year-old man with bacterial food poisoning due to Salmonella
      enteritidis, complicated by haemolitic-uraemic syndrome was described.

PMID- 10907374
TI  - [Thoracic aortic dissecting aneurysm with bleeding into the pleural cavity].
AB  - A rare case of dissecting aneurysm of the aortic arch with left haemothorax was
      presented. The authors describe modern methods of visualising diagnostics used in
      case of suspected dissecting aortic aneurysm.

PMID- 10907375
TI  - [Research from the Palliative Care Department in Poznan on treatment of neoplasm
      pain with Durogesic (transdermal fentanyl)].
AB  - Transdermal Fentanyl (TF, Durogesic) is a strong opioid analgesic which is used
      in the treatment of cancer pain. In this article we described basic properties
      and dosing guidelines for TF and our own experience with use of Durogesic in the
      treatment of cancer pain. In this open study TF was administered in 16 pts aged
      of 30-88 (mean 62 +/- 17) years with advanced cancer who suffered from strong
      cancer pain and who had previously been treated with morphine (11 pts),
      buprenorphine (1 pt), tramadol (2 pts) and non-opioid analgesics (2 pts).
      Analgesic efficacy and side-effects of TF were appraised. The time of the
      treatment was 7-235 (mean 77 +/- 58) days, the dose range 25-600 (mean 129 +/-
      117) micrograms/h. The mean initial dose of Durogesic was 94 +/- 99 micrograms/h
      and the final dose of fentanyl patch was 156 +/- 149 micrograms/h. Good analgesic
      effect was achieved in 11 pts (69%), partial effect in 2 pts (12%),
      unsatisfactory analgesia in 3 pts (19%). The treatment was well tolerated and the
      most frequent adverse reactions were constipation in 10 pts (63%) and drowsiness
      in 4 pts (25%). During the therapy with TF we didn't encounter serious side
      effects which would cause cessation of the treatment. Results of our study
      confirmed that TF was an effective analgesic most commonly used in pts with
      stable nociceptive pain especially when opioid analgesics could not be
      administered orally.

PMID- 10907376
TI  - [The gold foil filling--the indications and technic].

PMID- 10907378
TI  - 5th International Congress of Radiation Research. Seattle, Washington, USA. July
      13-20, 1974. Abstracts.

PMID- 10907377
TI  - [The aspiration and swallowing of foreign bodies. The management of the
      aspiration or swallowing of foreign bodies during dental treatment].
AB  - The purpose of this article is to draw attention to the possible complications of
      foreign body ingestion or aspiration associated with dental treatment, especially
      oral implant treatment. A guide for the management of swallowed or inhaled
      objects is given. When the object cannot be coughed out, then it is mandatory to
      take frontal and lateral chest roentgenograms to identify the object's position
      in the intestinal system or in the tracheobronchial tree. In case of ingestion,
      attempts should be made to recover the foreign object by esophagoscopy. Aspirated
      foreign bodies should be removed within 24 hours. Acute obstruction can be life
      threatening and delaying the removal of foreign objects may make a bronchoscopy
      technically more difficult. The clinician must be aware of the complications
      involved in accidentally inhaling or ingesting foreign bodies during dental
      treatment. Patients at greater risk of swallowing or aspirating foreign objects
      need to be identified and extra preventive steps must be taken to avoid such
      complications.

PMID- 10907379
TI  - The beginnings of medical oncology at the Mayo Clinic in Rochester.

PMID- 10907380
TI  - The epidemic of severe obesity: the value of surgical treatment.

PMID- 10907381
TI  - Prospective evaluation of Roux-en-Y gastric bypass as primary operation for
      medically complicated obesity.
AB  - OBJECTIVE: To determine prospectively the results of Roux-en-Y gastric bypass
      (RYGB) used as the primary weight-reducing operation in patients with medically
      complicated ("morbid") obesity. The RYGB procedure combines the advantages of a
      restrictive physiology (pouch of 10 mL) and a "dumping physiology" for high
      energy liquids without requiring an externally reinforced (banded) stoma.
      PATIENTS AND METHODS: Between April 1987 and December 1998, a total of 191
      consecutive patients with morbid obesity (median weight, 138 kg [range, 91-240
      kg]; median body mass index, 49 kg/m2 [range, 36-74 kg/m2]), all of whom had
      directly weight-related morbidity, underwent RYGB and prospective follow-up.
      RESULTS: Hospital mortality was 0.5% (1/191), and hospital morbidity occurred in
      10.5% (20/191). Good long-term weight loss was achieved, and patients adapted
      well to the required new eating habits. The mean +/- SD weight loss at 1 year
      after operation (113 patients) was 52 +/- 1 kg or 68% +/- 2% of initial excess
      body weight. By 3 years postoperatively (74 patients), weight loss was still 66%
      +/- 2% of excess body weight. Overall, 53 (72%) of 74 patients had achieved and
      maintained a weight loss of 50% or more of their preoperative excess body weight
      3 years after the operation. In addition, only 1 (1%) of 98 patients had
      persistent postoperative vomiting 1 or more times per week. CONCLUSION: We
      believe that RYGB is a safe, effective procedure for most patients with morbid
      obesity and thus may be the current procedure of choice in patients requiring
      bariatrics++ surgery for morbid obesity.

PMID- 10907382
TI  - Validation of death certificate diagnosis of out-of-hospital coronary heart
      disease deaths in Olmsted County, Minnesota.
AB  - OBJECTIVE: To evaluate the validity of death certificate diagnosis of out-of
      hospital (OOH) coronary heart disease (CHD) and sudden cardiac death (SCD) in
      Olmsted County, Minnesota, between 1981 and 1994. METHODS: In this review of the
      medical records, autopsy reports, and coroner's files, OOH deaths with heart
      disease as the underlying cause of death on the death certificate were classified
      into CHD (International Classification of Diseases, 9th Revision, Clinical
      Modification [ICD-9-CM] codes 410-414) and non-CHD (other ICD-9-CM heart disease
      codes) deaths. A 10% random sample (n = 174) of these death certificates was
      reviewed by physicians, and published validation criteria were applied to
      classify these deaths into validated CHD or non-CHD categories. Sudden cardiac
      death was defined as validated CHD that occurred at an OOH location with less
      than 24 hours between symptom onset and death. RESULTS: The death certificate
      definition of OOH CHD death (ICD-9-CM codes 410-414) had high sensitivity and
      positive predictive value of 91% and 96%, respectively. The specificity and the
      negative predictive value were slightly lower at 86% and 72%, respectively. The
      sensitivity of death certificate diagnosis of CHD for validated SCD was 89%, and
      the positive predictive value was 77%. Using a more restrictive definition of
      SCD, that is, less than 1 hour between the onset of symptoms and death, the
      positive predictive value of CHD codes for SCD was lower at 52%. CONCLUSIONS: In
      Olmsted County, the positive predictive values of death certificate diagnosis for
      OOH CHD and SCD are high. Relying on death certificate diagnoses results in about
      5% underestimation of the true CHD rates, whereas their use as a surrogate for
      SCD yields a 16% overestimation of the true SCD rates.

PMID- 10907383
TI  - A revised natural history model for primary sclerosing cholangitis.
AB  - OBJECTIVE: To describe a natural history model for primary sclerosing cholangitis
      (PSC) that is based on routine clinical findings and test results and eliminates
      the need for liver biopsy. PATIENTS AND METHODS: Using the Cox proportional
      hazards analysis, we created a survival model based on 405 patients with PSC from
      5 clinical centers. Independent validation of the model was undertaken by
      applying it to 124 patients who were not included in the model creation. RESULTS:
      Based on the multivariate analysis of 405 patients, a risk score was defined by
      the following formula: R = 0.03 (age [y]) + 0.54 loge (bilirubin [mg/dL]) + 0.54
      loge (aspartate aminotransferase [U/L]) + 1.24 (variceal bleeding [0/1]) - 0.84
      (albumin [g/dL]). The risk score was used to obtain survival estimates up to 4
      years of follow-up. Application of this model to an independent group of 124
      patients showed good correlation between estimated and actual survival.
      CONCLUSIONS: A new model to estimate patient survival in PSC includes more
      reproducible variables (age, bilirubin, albumin, aspartate aminotransferase, and
      history of variceal bleeding), has accuracy comparable to previous models, and
      obviates the need for a liver biopsy.

PMID- 10907384
TI  - The canalith repositioning procedure for the treatment of benign paroxysmal
      positional vertigo: a randomized controlled trial.
AB  - OBJECTIVE: To compare the canalith repositioning procedure (CRP) with a sham
      maneuver for the treatment of benign paroxysmal positional vertigo. PATIENTS AND
      METHODS: We recruited 50 patients with a history of positional vertigo and
      unilateral positional nystagmus on physical examination (Dix-Hallpike maneuver).
      Patients were randomized to either the CRP (n = 24) or a sham maneuver (n = 26).
      Measured outcomes included resolution of vertigo and positional nystagmus at
      follow-up examination. RESULTS: The mean duration of follow-up was 10 days for
      both groups. Resolution of symptoms was reported by 12 (50%) of the 24 patients
      in the CRP group and by 5 (19%) of the 26 patients in the sham group (P = .02).
      The results of the Dix-Hallpike maneuver were negative for positional nystagmus
      in 16 (67%) of 24 patients in the CRP group and in 10 (38%) of 26 patients in the
      sham group (P = .046). CONCLUSION: The CRP is effective treatment of benign
      paroxysmal positional vertigo, and this procedure can be performed by general
      internists on outpatients with this disorder.

PMID- 10907385
TI  - Addition of an anesthetic agent to enhance the predictability of the effects of
      botulinum toxin type A injections: a randomized controlled study.
AB  - OBJECTIVE: To determine whether the paralyzing effect of botulinum toxin type A
      reconstituted in a solution of lidocaine with epinephrine is as effective as that
      of the same toxin reconstituted in saline and to determine whether the addition
      of lidocaine with epinephrine enhances the predictability of outcomes of
      botulinum toxin injections. SUBJECTS AND METHODS: This double-blind, within
      subject, randomized controlled study was conducted in 10 volunteer subjects.
      Lidocaine was added to botulinum toxin type A to achieve an immediate paralyzing
      effect on the injected muscle, and epinephrine was added to minimize diffusion of
      the injected toxin to adjacent muscles. This combination of agents was injected
      to temporarily paralyze the frontalis, corrugator supercilii, and procerus
      muscles on 1 side of the forehead of the 10 volunteers. The contralateral side
      was injected with the same dosage of the toxin, reconstituted in an equal volume
      of saline, to serve as control. Photographic and video documentation of the
      drugs' effects was obtained before injection and at 5 to 10 minutes, 1 week, and
      3 months after the injections. RESULTS: Immediate paralysis ensued on the
      experimental side (botulinum toxin type A + lidocaine + epinephrine) in all 10
      volunteers. As assessed by 3 blinded evaluators, the extent of immediate
      paralysis resulting from the anesthetic agent was predictive of the extent of
      delayed paralysis resulting from the botulinum toxin. The botulinum toxin-induced
      paralysis wore off symmetrically in all subjects. CONCLUSION: The injection of
      botulinum toxin reconstituted in lidocaine with epinephrine provided the
      physician immediate feedback on the extent of paralysis to be expected from the
      chemodenervating action of the botulinum toxin. This may enhance the safety and
      predictability of botulinum toxin injections in many applications.

PMID- 10907386
TI  - Effects of 4 hand-drying methods for removing bacteria from washed hands: a
      randomized trial.
AB  - OBJECTIVE: To evaluate the effects of 4 different drying methods to remove
      bacteria from washed hands. SUBJECTS AND METHODS: One hundred adult volunteers
      participated in this randomized prospective study. All bacterial counts were
      determined using a modified glove-juice sampling procedure. The difference was
      determined between the amounts of bacteria on hands artificially contaminated
      with the bacterium Micrococcus luteus before washing with a nonantibacterial soap
      and after drying by 4 different methods (cloth towels accessed by a rotary
      dispenser, paper towels from a stack on the hand-washing sink, warm forced air
      from a mechanical hand-activated dryer, and spontaneous room air evaporation).
      The results were analyzed using a nonparametric analysis (the Friedman test). By
      this method, changes in bacterial colony-forming unit values for each drying
      method were ranked for each subject. RESULTS: The results for 99 subjects were
      evaluable. No statistically significant differences were noted in the numbers of
      colony-forming units for each drying method (P = .72). CONCLUSION: These data
      demonstrate no statistically significant differences in the efficiency of 4
      different hand-drying methods for removing bacteria from washed hands.

PMID- 10907387
TI  - Methylphenidate: its pharmacology and uses.
AB  - Methylphenidate is a commonly used medication in the United States. This central
      nervous system stimulant has a mechanism of action distinct from that of
      amphetamine. The Food and Drug Administration has approved methylphenidate for
      the treatment of attention-deficit/hyperactivity disorder and narcolepsy.
      Treatment with methylphenidate has been advocated in patients with traumatic
      brain injury and stroke, cancer patients, and those with human immunodeficiency
      virus infection. Placebo-controlled trials have documented its efficacy as an
      adjunctive agent in the treatment of depression and pain. This article reviews
      the current understanding of the mechanism of action and efficacy of
      methylphenidate in various clinical conditions.

PMID- 10907388
TI  - Albert Szent-Gyorgyi--Nobel laureate.

PMID- 10907389
TI  - Lymphadenopathy.
AB  - Lymphadenopathy can occur in any age group, in symptomatic or asymptomatic
      patients, and in a single site or at multiple sites. Lymphadenopathy is
      associated with numerous disorders. An abnormal lymph node may be observed or
      palpated by the patient, found by a health care worker, or discovered through
      radiologic evaluation. Lymphadenopathy may be a part of a complex case
      presentation, or the clinical cause may be straightforward. Patients with
      potentially curable malignant disorders may have lymphadenopathy as the first
      sign of their disease. This review of lymphadenopathy summarizes general
      considerations, discusses which patients might be considered for biopsy, reviews
      which nodes are most likely to be diagnostic, outlines initial diagnostic
      considerations on a region-by-region basis, and reviews a broad differential
      diagnosis for adenopathy.

PMID- 10907390
TI  - Nonalcoholic steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) is a liver disease that, until recently, has
      been underrecognized as a common cause of elevated liver enzymes. This distinct
      clinical entity is characterized by liver biopsy findings similar to those seen
      in alcoholic hepatitis but in the absence of alcohol consumption sufficient to
      cause such changes. Patients with NASH are often middle-aged and obese, with
      coexisting diabetes or hyperlipidemia, but NASH also occurs in younger lean,
      otherwise healthy individuals and even in children. Although NASH is generally a
      benign disorder, it may be progressive, leading to cirrhosis and complications of
      portal hypertension. Liver biopsy remains the gold standard for diagnosis.
      Therapy for NASH remains poorly defined, although weight reduction and
      ursodeoxycholic acid may have a beneficial effect.

PMID- 10907391
TI  - Phantom limb pain as a manifestation of paclitaxel neurotoxicity.
AB  - Paclitaxel is a chemotherapeutic agent with activity directed against several
      malignancies. It has multiple adverse effects including neurotoxicity. We
      describe 2 patients with prior amputation who experienced phantom limb pain (PLP)
      after receiving paclitaxel therapy. A third patient experienced disabling
      neurotoxicity in the extremity of a prior ulnar nerve and tendon transposition
      after receiving paclitaxel. This unique syndrome should be identified as a direct
      causal effect of paclitaxel. In this report, we review the pathophysiology of PLP
      and treatment options. Physicians should be aware that PLP can occur after
      initiation of paclitaxel.

PMID- 10907392
TI  - Calcified left ventricular mass: unusual clinical, echocardiographic, and
      computed tomographic findings of primary cardiac osteosarcoma.
AB  - Primary cardiac osteosarcomas are rare and usually originate in the left atrium.
      In contrast, osteosarcomas metastatic to the heart most commonly involve the
      right cardiac chambers. This case report describes an unusual primary cardiac
      osteosarcoma, initially observed as a slowly growing, densely calcified mass of
      the left ventricle with subsequent secondary pulmonary metastasis. Although
      cardiac tumors may be asymptomatic, this patient had recurrent bouts of
      ventricular tachyarrhythmia. We describe the clinical, echocardiographic, and
      radiological observations spanning 6 years and the gross and microscopic features
      at autopsy.

PMID- 10907393
TI  - Pneumococcal vaccine in patients with absent or dysfunctional spleen.
AB  - Four patients (3 long-term Hodgkin disease survivors and 1 recipient of an
      allogeneic bone marrow transplant) developed severe infections with Streptococcus
      pneumoniae after staging splenectomy or due to functional hyposplenism after
      total body irradiation and bone marrow transplantation. Current guidelines for
      prevention of infection recommend pneumococcal immunization for patients with
      Hodgkin disease treated with splenectomy and others with functional hyposplenism.
      Booster vaccination after 5 years is also advised. Hospital- and community-based
      vaccination initiatives may help identify at-risk patients.

PMID- 10907394
TI  - Myiasis due to Hypoderma lineatum infection mimicking the hypereosinophilic
      syndrome.
AB  - Myiasis is the infestation of live humans with larvae of Diptera (true flies).
      This report describes a protracted illness caused by infestation with Hypoderma
      lineatum, resembling the hypereosinophilic syndrome. A 35-year-old man had a 9
      month multisystemic illness with pronounced eosinophilia, pleuritis,
      pericarditis, and myositis. Treatments including glucocorticoids did not alter
      the disease. Diagnostic studies included computed tomography, 2-dimensional
      echocardiography, leukocyte count, surgical biopsy of skin and muscle, blood
      immunoglobulin levels, and blood chemistry. Myiasis was recognized when a worm
      emerged from the patient's skin; after a second worm emerged, the patient's
      symptoms disappeared rapidly. Other determinations included IgE and IgG levels
      specific for H lineatum, Western blot, and immunofluorescence for eosinophil
      major basic protein; IgG antibodies to H lineatum decreased after emergence of
      the worms. The patient's symptoms mimicked the hypereosinophilic syndrome but
      resolved when the myiasis became apparent. Specific serologic analyses can
      identify infected patients, and ivermectin may be useful as treatment.

PMID- 10907395
TI  - 54-year-old man with dyspnea and abdominal wall bruising.

PMID- 10907396
TI  - Hope and the medical encounter.

PMID- 10907397
TI  - Transfusion safety.

PMID- 10907398
TI  - [The biomechanical function of the heart and its adrenergic regulation after long
      term gamma radiation exposure].
AB  - The study of heart isolated by Langendorf's method has shown that the prolonged
      gamma irradiation of rats with 1.0 Gy dose (2.8 x 10(-7) Gy/sec) causes the
      decrease in contraction and relaxation ability, of myocardium, reduces functional
      response of heart to the stimulation of beta-adrenergic receptors, and increases
      of myocardium reaction to the stimulation of alpha-adrenergic receptors.

PMID- 10907399
TI  - [The dynamics of folliculogenesis in the ovary of the progeny of animals
      irradiated in embryogenesis and early postnatal life].
AB  - The prolonged irradiation with 1.0 Gy dose in prenatal and early postnatal
      periods of development of rats leads to the disturbance in the rate of follicular
      growth, the reduction of their pool, mainly the pool of young forms of oocytes.
      Processes of degeneration and destruction occur and develop in the ovary of both
      the irradiated rats and their first progeny.

PMID- 10907400
TI  - [The effect of the biochemical adaptations in the Manchu alder (Duschecia
      fruticosa (Rupr)) to an elevated natural radiation background on the
      survivability of seedlings and on the radiosensitivity of its seeds].
AB  - Seeds and sprouts of bushy alder existing for long under the condition of the
      enhances natural radiation background (ENRB; from 1.4 to 72.0 mCu/(kg.s)) have
      been examined to determine biochemical adaptations to permanent low-level
      irradiation. To achieve this goal a combined cytological and biochemical
      technique for the assessment of the activity of genome of the sprout root
      meristem in response to translation, replication and reparation has been applied.
      The activity of antioxidant systems has been studied. The data obtained allow us
      to reveal mechanisms of alder bush biochemical adaptations to various ENRB rates
      and their effect upon seeds radiosensitivity and sprouts survival. It is
      determined that the increase in sprout vitality and high radioresistance of seeds
      ripened under the conditions of low-level natural radiation is due to the content
      of low molecular antioxidants and activation of systems of genome reparation.

PMID- 10907401
TI  - [The effect of ionizing radiation in a wide dosage range on the structural
      functional characteristics of the protein and lipid components of erythrocyte
      plasma membranes].
AB  - The erythrocyte ghosts were irradiated with doses of 4 x 10(-3) Gy-10(3) Gy.
      Changes in the membrane lipid microviscosity, membrane proteins' structural
      mobility, membrane surface potential and intensity of the lipid peroxidation
      processes were determined. It has been established that the features of membrane
      structural changes are characterised, by polyphase changes of examined
      parameters.

PMID- 10907402
TI  - [The neuromediator modulation of the ionic composition of the brain cells in rats
      irradiated at nonlethal doses].
AB  - It had been found that both the single prolonged irradiation and chronic
      (fractionated) one with doses of 25 and 50 cGy (1.75 mGy/min) caused essential
      modification of the biphase modulative effects of acetylcholine and gamma
      aminobutyric acid upon K+ level in rat brain cortex slices to be compared to the
      acute lethal irradiation influence. The results of model experiments showed
      saturated fatty acids to be significant for the changes in regulative functions
      of nerve cell membranes after exposure to low dose-rate radiation.

PMID- 10907404
TI  - [An experimental study of the role of a blockade of serotonin 5-HT3 receptors and
      dopamine D2 receptors in the mechanism of the occurrence of early radiation
      vomiting in monkeys].
AB  - The experiments with M. fasciculata monkeys exposed to 137Cs gamma-radiation with
      a dose of 6.9 Gy showed that Latranum, a blocker of serotonin 5-HT3 receptors, is
      a more efficient antiemetic than Dimetphramidum, a D2 dophamin lytic. This is
      suggested by fewer animals with emetic reaction of by less severe vomiting in
      case they have any. The results agree well with a hypothesis that serotonin
      receptors are dominant in the chemoreceptor trigger zone of monkeys.

PMID- 10907403
TI  - [An experimental study of the role of prostaglandins in the mechanism of the
      occurrence of dyspeptic disorders during the primary reaction after body exposure
      to ionizing radiation at large doses].
AB  - The experiments with dogs exposed to 100 Gy of accelerated electrons demonstrated
      a significant role of prostaglandins in the origin of early post-radiation
      dyspepsia. Their significance for genesis of post-radiation dyspeptic disturbance
      caused by exposure to superhigh doses becomes clear-cut when a combination of an
      antiemetic and inhibitors of prostaglandin biosynthesis is used. A study of the
      effect of dexamethasone, a blocker of arachidonic acid release, and of voltaren,
      an inhibitor of prostaglandin formation from cyclic endoperoxide, suggests that
      it would be appropriate to prevent radiation vomiting and diarrhea by inhibiting
      both of the above stages in prostaglandin biosynthesis.

PMID- 10907405
TI  - [Variability in the longevity of Drosophila imagoes under chronic irradiation at
      low doses].
AB  - The investigation of life span variability induced by a chronic influence of low
      doses gamma irradiation on the laboratory stocks of D. melanogaster,
      distinguishing by mobile genetic units, were carried out. Shown was the link of
      life span alterations in D. melanogaster with features of cytotype and genotype
      in tested stocks and with induced apoptotic cell death. The life span variation
      can be determined by a genomic destabilisation with an induction of mobile
      genetic elements in conditions of chronic gamma irradiation.

PMID- 10907406
TI  - [The systemic response of antioxidant enzymes to the oxidative stress induced by
      irradiation at low doses].
AB  - As a result of total chronic gamma irradiation of mice (137Cs, 0.6 cGy/day, 9
      days) the functioning of superoxide generation and utilisation systems in liver
      were disturbed. The regulatory links between the activities of superoxide
      dismutase and glutathione peroxidase are found to be maintained. Postradiation
      effects were more expressed for a total dose of 1.2 cGy than for a dose of 5.4
      cGy, providing support for the hypothesis of delayed reparation as a reason of
      harmful action of low-dose irradiation.

PMID- 10907407
TI  - [The possibilities of sensitized photomutagenesis for the induction of genetic
      variability in plants].
AB  - It was found that combined influence of sensitizers and laser emission on
      vegetation under some conditions induces marked mutagenesis. The observed
      synergism was analysed. The possible mechanisms of the phenomenon was considered.
      A unified approach was proposed to assess efficacy of sensitizer-laser pairs by
      fragmentation DNA. The recommendations were given for application of combined
      action of sensitizers and laser emission for experimental mutagenesis.

PMID- 10907408
TI  - [Nuclei with protrusions--"tailed" nuclei--and radiation cytogenetic markers in a
      lymphocyte culture after x-ray irradiation].
AB  - Frequency of the appearance of binuclear cells with nuclei having outgrowth into
      the cytoplasmic space and arise after first mitosis in human lymphocyte culture
      is linear-square dependent on the X-irradiation at doses from 0.0 to 4.0 Gy.
      Positive correlation between frequency of cells with "tailed" nuclei and
      frequency of metaphases of first mitosis having dicentrics and rings was
      established. Apparently, formation such "tailed" nuclei is connected with
      dicentrics and rings.

PMID- 10907409
TI  - [Changes in the EPR spectra of the nitrosyl complexes of blood proteins in the
      low-intensity whole-body irradiation of mice].
AB  - After NO adding to mice blood and isolated erythrocytes ESR signal of nitrozyl
      complex HbNO (g = 2.07, g = 1.98) and NO-induced MetNg (g = 6.0) were registered.
      It was shown that the intensity of ESR spectra of these complexes increased after
      radiation of mice with a dose of 0.06, 0.6 and 5.4 cGy. Low-dose irradiation (0.6
      and 0.06 cGy) caused the change in the form of ESR spectra of HbNO (g = 2.07),
      which is indicative of the shift from T-structure to R-structure and of the
      preferred formation of R-conformations of oxyhemoglobin in blood. It was found
      that dependence of NO-induced MetHb signal on irradiation dose is bimodal that
      may be connected with nonlinear response of the cells to irradiation and retarded
      adaptive response after radiation with low doses.

PMID- 10907410
TI  - [The postradiation use of vitamin-containing complexes and a phycocyanin extract
      in a radiation lesion in rats].
AB  - Wistar rats have been exposed to X-rays with a dose of 5 Gy. Significant decrease
      in dehydrogenase activity, energy-rich phosphate level and efficiency of
      antioxidant defence and significant increase in pyruvate amount were observed
      within 4 weeks. It was also found that the feeding of exposed rats with
      phycocyanin extract from blue-green algae Spirulina platensis lead to correcting
      effect. The same result was observed after injections of tocopherol or complex of
      six water-soluble vitamins. The combination of above mentioned compounds had more
      marked effect, especially at the presence unitiole and Na2Se.

PMID- 10907411
TI  - [The synthetic peptide D-(iEW) (thymodepressin) protects bone marrow CFU-S from
      ionizing radiation exposure].
AB  - Synthetic polypeptide D-(iEW) (Thymodepressin) was shown to reduce the bone
      marrow CFU-S in the S-phase of cell cycle. Apparently, due to this property the
      agent being administered 2 days before the irradiation with 4 Gy causes a
      prominent restoration of the CFU-S population afterwards. The 3-5 times higher
      value of this parameter as compared to the control (irradiation only) is likely
      to be connected to the increased "survival" of the Thymodepressin-protected CFU-S
      after the treatment with ionizing irradiation.

PMID- 10907412
TI  - [The effect of magnetic fields on the growth and division of the lon mutant of
      Escherichia coli K-12].
AB  - It was shown that the static magnetic field (SMF) and electromagnetic field (EMF)
      caused inhibition of the cell division in Escherichia coli K-12 lon mutant. The
      low-frequency EMF 4 Hz led to the 20% survival, but EMF at 50 Hz increased the
      survival of cells up to 53%. After exposure to magnetic field cells lost capacity
      for division and grow as filaments, unable to form the colonies on the solid
      media.

PMID- 10907413
TI  - [The formation of absorbed doses of 137Cs in the body of the female and her
      progeny during suckling].
AB  - The transfer of 137Cs with maternal milk to progeny was studied in rats. The rats
      were administered with 25 kBq/g of 137Cs nitrate (pH = 6) in a single oral dose
      immediately after delivery. Nonpregnant females served as control. Absorbed doses
      per activity unit to lactating rats were 23% lover than to nonlactating ones.
      Over the suckling period, absorbed doses to young rats amounted to about 35% of
      the absorbed dose to the nursing female. For nonlactating females, the internal
      dose approximately equalled the sum of doses to the nursing female and young
      rats.

PMID- 10907414
TI  - [The phospholipid composition of the liver in root voles living under different
      radioecological conditions].
AB  - The effect of the increased natural radiation background (within some areas in
      Komi Republic) and man-caused radioactive contamination in the Chernobyl NPP
      accident zone on the composition of liver phospholipids in Microtus oeconomus
      inhabiting these areas was studied. The significant changes in the liver lipid
      composition in rodents inhabiting both the Chernobyl accident zone and the areas
      with the increased natural radiation background were found. The maximal changes
      in the liver phospholipid composition were revealed during the first year after
      the accident. The reverse dependence between the phosphatidyl
      choline/phosphatidyl ethanolamine ratio and the ratio between the sum of more
      readily oxidizable phospholipids and the sum of more poorly oxidizable ones was
      found. However, the slope of corresponding curves significantly depends on the
      radioactive state in the area of the population inhabitance. The conclusion about
      high sensitivity of the lipid composition of hepatocytes in Microtus oeconomus
      both to the impact of the man-caused radioactive contamination and the increased
      level of the natural radioactivity was drawn.

PMID- 10907415
TI  - [The antioxidant status of the seeds in populations of the great plantain
      (Plantago major L.) growing in an area exposed to the Balakovo Atomic Electric
      Power Station and to chemical enterprises].
AB  - The results of the determination of radionuclide and chemical (multielement
      analysis) soil pollution are presented. The data on antioxidant status of
      plantain (Plantago major L.) in conjunction with the data on radionuclide and
      chemical pollution are analyzed. The most significant decrease in antioxidant
      activity of plant seeds was observed in areas situated along the most frequent
      wind direction in the region in summer 1998. It is suggested that lower
      antioxidant status is caused by the chronic radionuclide release on the
      chemically polluted territories.

PMID- 10907416
TI  - [The basic research results in the field of radiobiology and radioecology for
      1999].

PMID- 10907417
TI  - Combined effects of ethanol, high homogenization pressure, and temperature on
      cell fatty acid composition in Saccharomyces cerevisiae.
AB  - The specific aims of this research were to evaluate the combined effects of
      ethanol and high-pressure homogenization at different temperatures on cell
      viability in Saccharomyces cerevisiae and to study the induced modification of
      fatty acid composition. The decrease in viability was weak at 10 degrees C while
      a homogenization pressure over 1000 bar (1 bar = 100 kPa) induced a significant
      reduction in viability when the cells were incubated at 20 and 30 degrees C. The
      cell tolerance to pressure decreased with an increase in ethanol concentration
      and temperature. Ethanol, particularly intracellular ethanol accumulated by S.
      cerevisiae, played an important role in the response to homogenization pressure
      and in modification of the cell fatty acid composition. In fact, an unusually
      elevated accumulation of ethyl esters in lipid extracts of yeast cells subjected
      to high homogenization pressure, especially in the presence of exogenous ethanol
      and at 30 degrees C, was observed. Moreover, only unsaturated and traces of short
      chain fatty acids were esterified with ethanol.

PMID- 10907418
TI  - Activation and fragmentation of Bacillus thuringiensis delta-endotoxin by high
      concentrations of proteolytic enzymes.
AB  - Commercial enzymes and insect gut juice at various concentrations were used to
      digest Bacillus thuringiensis subsp. sotto Cry1Aa protoxin and examine the
      fragmentation pattern and effect on insecticidal activity. Trypsin at both high
      (5 mg/mL) and low (0.05 mg/mL) concentrations converted protoxin to toxin with no
      difference in insecticidal activity against Bombyx mori larvae. In both cases,
      the toxin protein had an apparent M(r) of 58.4 kDa (SDS-PAGE). Active toxin of
      identical M(r) was also produced with low concentrations of Pronase and
      subtilisin, but at high concentration, it was degraded into two protease
      resistant fragments of apparent M(r) 31.8 and 29.6 kDa, and exhibited no
      insecticidal activity. Sequencing data established the primary cleavage site to
      be in domain II, the receptor-binding region of the toxin, in an exposed loop
      between two beta-sheet strands. Fragmentation was not observed, however, when the
      digests were analyzed by native protein techniques, but rather the toxin molecule
      appeared to be intact. The amount of activated toxin produced by Choristoneura
      fumiferana gut juice was markedly reduced when the gut-juice concentration was
      increased from 1 to 50% and correlated with a loss in insecticidal activity.
      However, no lower M(r) protease-resistant fragments were evident in the SDS-PAGE
      of these digests.

PMID- 10907419
TI  - Impact of an urban effluent on the bacterial community structure in the Arga
      River (Spain), with special reference to culturable gram-negative rods.
AB  - The Arga River is an interesting system in which to study the impact of urban
      effluent pollution because it receives a single effluent in the form of
      wastewater discharge from the city of Pamplona. To analyze the extent of this
      discharge, total bacteria, culturable heterotrophic bacteria, and Gram-negative
      heterotrophic bacteria were enumerated and 409 isolates of the latter were
      identified. One sampling station was located upstream from the inflow, while five
      were located up to 30 km downstream. Bacterial counts increased drastically
      downstream from the wastewater inflow. Total bacterial numbers decreased along
      the 30 km downstream, the last station attaining similar values to those recorded
      upstream from the discharge. However, culturable heterotrophic and Gram-negative
      heterotrophic bacteria levels generally remained significantly higher within the
      30 km zone investigated. Among the 409 isolates identified, Aeromonas spp. were
      the most frequent both upstream and downstream from the discharge. In contrast,
      although strains belonging to different genera of Enterobacteriaceae were found
      in all stations, their occurrence was significantly higher just downstream from
      the polluted discharge. Acinetobacter spp., which were never found upstream, were
      detected in all stations below the discharge. Our results clearly show that the
      bacterial community structure changes definitively downstream from the discharge
      and that Aeromonas were common throughout the sampling zone. Thus they cannot be
      considered good indicators of pollution in this setting compared to some genera
      of Enterobacteriaceae or some species of Acinetobacter, the distribution of which
      correlated better with the distance from the wastewater discharge.

PMID- 10907420
TI  - Purification and characterization of 2-ethoxyphenol-induced cytochrome P450 from
      Corynebacterium sp. strain EP1.
AB  - A soluble cytochrome P450 (P450EP1A) induced by 2-ethoxyphenol was purified to
      apparent homogeneity from Corynebacterium sp. strain EP1. The P450EP1A showed a
      single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a
      molecular weight of about 45 kDa. The CO-reduced difference spectra of P450EP1A
      had a Soret maximum at 447.6 nm. The substrate difference spectra with 2
      ethoxyphenol showed an absorption maximum at 394.0 nm. The purified P450EP1A
      degraded 2-ethoxyphenol in an assay system composed of spinach ferredoxin-NADP+
      oxidoreductase and NADPH. The reaction activity decreased to 1.4% of its original
      activity by addition of CO. The existence of catechol in the reaction mixture was
      confirmed after the metabolic reaction, indicating that P450EP1A catalyzes O
      dealkylation of 2-ethoxyphenol. In addition to 2-ethoxyphenol, the P450EP1A
      metabolized 2-methoxyphenol, 1,1,1-trichloroethane, carbon tetrachloride,
      benzene, and toluene.

PMID- 10907421
TI  - Degradation of 2,4-dinitrophenol and selected nitroaromatic compounds by
      Sphingomonas sp. UG30.
AB  - Sphingomonas strain UG30 mineralizes both p-nitrophenol (PNP) and
      pentachlorophenol (PCP). Our current studies showed that UG30 oxidatively
      metabolized certain other p-substituted nitrophenols, i.e., p-nitrocatechol, 2,4
      dinitrophenol (2,4-DNP), and 4,6-dinitrocresol with liberation of nitrite. 2,6
      DNP, o- or m-nitrophenol, picric acid, or the herbicide dinoseb were not
      metabolized. Studies using 14C-labelled 2,4-DNP indicated that in glucose
      glutamate broth cultures of UG30, greater than 90% of 103 microM 2,4-DNP was
      transformed to other compounds, while 8-19% of the 2,4-DNP was mineralized within
      5 days. A significant portion (20-50%) of the 2,4-DNP was metabolized to highly
      polar metabolite(s) with one major unidentified metabolite accumulating from 5 to
      25% of the initial radioactivity. The amounts of 2,4-DNP mineralized and
      converted to polar metabolites was affected by glutamate concentration in the
      medium. Nitrophenolic compounds metabolized by UG30 were also suitable substrates
      for the UG30 PCP-4-monooxygenase (pcpB gene expressed in Escherichia coli) which
      is likely central to degradation of these compounds. The wide substrate range of
      UG30 could render this strain useful in bioremediation of some chemically
      contaminated soils.

PMID- 10907422
TI  - Specific mucosal immunity in the pathophysiology of bacterial prostatitis in a
      rat model.
AB  - Mucosal immunity was established in the rat prostate by stimulating the common
      mucosal system through serosal exposure of formalin-killed Escherichia coli.
      Immunized but not sham-immunized rats developed bacterial specific IgG and IgA in
      prostatic fluid, and IgA in urine. Immunized (n = 21) and sham-immunized control
      rats (n = 30) were challenged by transurethral injection of E. coli into the
      prostate ducts. Mortality, gross and microscopic pathology, tissue bacterial
      counts, bacterial associated immunoglobulins, and antibody titers in serum and
      urine were assessed at 7 days following the challenge. Increased E. coli specific
      immunoglobulin titers were seen in immunized rats, and E. coli, but not Proteus,
      found in the prostates of immunized animals were coated with IgG and IgA.
      Immunization protected against toxaemia and septicemia, seen as a rare
      complication of acute prostatitis, but did not protect against acute prostatitis,
      nor alter the degree of tissue damage seen in the rat model.

PMID- 10907423
TI  - A simple rapid procedure for obtaining axenic cultures from monoxenic cultures of
      myxomycete plasmodia.
AB  - Axenic culture of myxomycete plasmodia has been attempted from time to time by
      various authors, but with very little success. From over 500 known species of
      myxomycetes, fewer than 20 species have been reported in axenic culture to date,
      including axenic myxamoebal cultures. In these cultures, the plasmodia required
      either complex media, or a killed bacterial supplement for growth. Furthermore,
      the time required for attaining the axenic state varied from several months to
      years. In the present study, a simple, rapid procedure has been developed to
      render monoxenic plasmodial cultures axenic. This procedure is based on our
      discovery that plasmodia have certain unusual substrate preferences that are
      inhibitory to the associated bacteria using Physarella oblonga as a model. The
      presence or absence of the bacteria could be ascertained through incubation in
      four different bacteriological media and by the use of a differential staining
      technique.

PMID- 10907425
TI  - Diversity of culturable heterotrophic aerobic bacteria in pristine stream bed
      sediments.
AB  - More than 900 culturable, heterotrophic aerobic isolates were obtained from the
      sediments of a forested, pristine stream and analyzed using three classical
      microbiological tests: API 20E, amplified ribosomal DNA restriction analysis
      (ARDRA), and fatty acid analysis. Gram-negative bacteria comprised most of the
      heterotrophic aerobic isolates (66.7%), similar to other oligotrophic
      environments. The isolates were assigned to the genus level as Pseudomonas,
      Flavobacterium, Micrococcus, Bacillus, Chromobacterium, Acinetobacter,
      Alcaligenes, Aeromonas, Methylobacterium, Enterobacter, Corynebacterium, and
      Sporolactobacillus. Genotypic analysis by ARDRA facilitated the comparison among
      strains within Pseudomonas, Bacillus, and Enterobacter groups. Temperature and
      predation may influence the survival of bacteria during seasons, as shown
      previously by others. Our results showed that the number of heterotrophic aerobic
      bacteria, especially Enterobacter, Alcaligenes, and Aeromonas, and Gram-positive
      bacteria, decreased in winter compared to summer conditions.

PMID- 10907424
TI  - Use of spectrophotometric reading for in vitro antifungal susceptibility testing
      of Aspergillus spp.
AB  - A comparative study of visual and spectrophotometric MIC endpoint determinations
      for antifungal susceptibility testing of Aspergillus species was performed. A
      broth microdilution method adapted from the National Committee for Clinical
      Laboratory Standards (NCCLS) was used for susceptibility testing of 180 clinical
      isolates of Aspergillus species against amphotericin B and itraconazole. MICs
      were determined visually and spectrophotometrically at 490 nm after 24, 48, and
      72 h of incubation, and MIC pairs were compared. The agreement between the two
      methods was 99% for amphotericin B and ranged from 95 to 98% for itraconazole. It
      is concluded that spectrophotometric MIC endpoint determination is a valuable
      alternative to the visual reference method for susceptibility testing of
      Aspergillus species.

PMID- 10907426
TI  - Cloning and analysis of the aroB gene encoding dehydroquinate synthase from
      Corynebacterium glutamicum.
AB  - The aroB gene encoding dehydroquinate synthase of Corynebacterium glutamicum has
      been cloned by complementation of an aro auxotrophic mutant of Escherichia coli
      with the genomic DNA library. The recombinant plasmid contained a 1.4-kb fragment
      that complemented the Escherichia coli dehydroquinate-synthase-deficient mutant.
      The nucleotide sequences of the subcloned DNA has been determined. The sequences
      contain an open reading frame of 360 codons, from which a protein with a
      molecular mass of about 38 kDa could be predicted. This is consistent with the
      size of the AroB protein expressed in E. coli. Alignment of different prokaryotic
      and eukaryotic aroB gene products reveals an overall identity ranging from 29 to
      57% and the presence of several highly conserved regions.

PMID- 10907427
TI  - Guidance on the assessment of the efficacy of toothpastes. FDI Commission. Work
      Project (8-95).

PMID- 10907428
TI  - Tooth extraction in HIV sero-positive patients.
AB  - Tooth extraction is the dental treatment most commonly carried out among HIV
      positive patients. In this paper we propose a simple protocol for dental
      extractions in patients of this type, based on a review of the literature and on
      our own experience in this field. The factors to be considered when planning a
      dental extraction for HIV positive patients are: diagnosis of the lesion
      justifying the need for tooth extraction and medical assessment of the patient
      including the infection pathway, the stage of the disease, laboratory tests and
      drug therapy. The most frequent post extraction complications are a delay in the
      wound healing process, alveolitis and surgical wound infection. Fortunately,
      these complications tend to be rather uncommon and not too severe; they can be
      managed on an out-patient basis and their prevalence will probably tend to
      decrease with the introduction of the new anti-retroviral drugs for HIV-1.

PMID- 10907429
TI  - Analysis of prevalence and trends of dental caries in the Americas between the
      1970s and 1990s.
AB  - Data on the prevalence and severity of dental caries collected by country members
      of the Pan American Health Organisation (PAHO) were summarised to analyse current
      status and trends since the 1970s. The mean number of decayed, missing, and
      filled teeth (DMF-T) among 12-year-old children and the relative contribution of
      each DMF-T component were collected from official reports and publications in the
      scientific literature. Overall, a secular trend toward lower caries prevalence
      was observed in most countries, more notably among those with large prevention
      programmes using fluorides. Many countries have reached the World Health
      Organization (WHO) year 2000 goal of a mean DMF-T of < or = 3 but others are
      still far from reaching that goal. Few countries have reached the status of
      having large proportions of disease prevalence localised in a small percentage of
      the population, a pattern observed as prevalence decreases. Since 1994, PAHO's
      Regional Oral Health Program has developed two strategies to address these
      issues: the introduction and reinforcement of national preventive programmes
      using fluorides and the introduction of the atraumatic restorative treatment
      (ART).

PMID- 10907430
TI  - Anxiety and cortisol excretion correlate prior to dental treatment.
AB  - The aim of this study was to investigate the possible relationship between dental
      anxiety and cortisol excretion prior to dental treatment. Trait and state dental
      anxiety of male subjects were determined using the Dental Anxiety Scale (DAS) and
      a visual analogue scale (VAS), respectively. Urine and stimulated parotid saliva
      were collected immediately before dental treatment sessions. Cortisol levels were
      determined by radioimmunoassay. The self-reported trait dental anxiety (= DAS
      score) showed a significant relation to the urinary cortisol excretion. The
      salivary cortisol concentration did not correlate with either VAS or DAS score.
      The data suggest that dental anxiety has a long-term effect on cortisol
      metabolism of patients. Therefore, measurement of the cortisol concentration in
      urine, which reflects a longer term response to stress, seems a promising
      parameter in the investigation of dental anxiety.

PMID- 10907432
TI  - Reasons for extraction of permanent teeth in Jordan.
AB  - This investigation was carried out to determine the reasons for extraction of
      permanent teeth in Jordan. A random sample of 200 Jordanian Dentists (1:10) were
      asked to record reasons for the extraction of permanent teeth during a two week
      period. Of the 139 dentists responding, only 97 dentists extracted teeth during
      the study period. A total of 934 teeth were extracted from 582 patients, of these
      33.4 per cent were extracted for periodontal disease, and 27.6 per cent because
      of caries and its sequelae. The study suggests caries and its consequences
      affected tooth loss throughout life while the rate of tooth loss due to
      periodontal disease increases with age.

PMID- 10907431
TI  - Comparison of the abrasive wear resistance between amalgams, hybrid composite
      material and different dental cements.
AB  - This paper reports on the abrasion wear of various restorative dental materials
      (three amalgams and two dental cements and a hybrid composite material) commonly
      used in dentistry. The mechanical properties, surface roughness and the volume
      loss by abrasion were determined for the different materials studied. The results
      showed a better profile for the amalgams versus the composite materials due to
      the failure of the polymeric matrix of the latter materials. However, the
      amalgams exhibited corrosion observed by means of Scanning Electron Microscopy.

PMID- 10907433
TI  - Demography and seasonal variation of acute necrotising gingivitis in Nairobi,
      Kenya.
AB  - The objectives of this study were to determine the frequency of Acute Necrotising
      Gingivitis (ANG), its sex and age distribution, ethnicity and seasonal variation
      amongst patients at the Dental Unit of Kenyatta National Hospital (KNH) in
      Nairobi, Kenya. Cards of patients who were seen in the Dental Unit of KNH in
      1992/1993, were scrutinised for positive diagnosis of ANG, age, sex, presenting
      signs and symptoms and treatment that was given. Of the 53,572 patients who were
      treated, (0.15 per cent) had ANG. Their age range was 1.5-46 years (Mean = 14.5
      years), with 58.5 per cent being below 11 years and 32.9 per cent being between
      21 and 40 years. The most affected ethnic groups were the Luos and Kikuyus, while
      72 per cent of the patients were seen in March and April, and between September
      and December. It is concluded that the frequency of ANG was low, ANG affected
      children and adults, and that ANG varied seasonally.

PMID- 10907434
TI  - Morphology of initial lesions of enamel treated with different commercial
      dentifrices using a pH cycling model: scanning electron microscopy observations.
AB  - The aim of this study was to evaluate and compare the 'calcium fluoride-like
      reaction products' formed, both on the surface and in the subsurface caries-like
      lesions of enamel, from different commercial dentifrices manufactured locally
      from developed and developing countries. The experiment was conducted by using
      the in vitro single-section technique under the pH-cycling system used for 10
      days. The tested dentifrices include; Maxam DFP Maxam Tartar Controls, First,
      Tianqui Medicated (China); Vicco Vajradenti (India); Colgate MFP2. Crest Tartar
      Control (USA); and a non-fluoride dentifrice, Jie Yin (China) used as control.
      The surface and subsurface of the lesions, before and after treatment, were
      examined using scanning electron microscopy. Varying degrees of fine globular
      patterns of calcium fluoride-like material were observed on the enamel surfaces
      of five out of eight groups and in the subsurface of four groups. Two treatment
      groups showed a 'similar appearance' compared with the control and untreated
      groups. This study suggests and supports that, when compared with 'multinational
      dentifrices', some Chinese and Indian dentifrices manufactured locally failed to
      induce the typical morphological appearance of globules as seen with fluoride
      dentifrices.

PMID- 10907435
TI  - In vitro corrosion behaviour and metallic ion release of different prosthodontic
      alloys.
AB  - The corrosion resistance for six metallic alloys often used in clinical
      dentistry, was evaluated by measuring their polarisation resistance in an
      artificial saliva environment. The critical current density (icr), the passive
      current density (ip), the corrosion potential (Ecorr) and the critical pitting
      potential (Ecp), were studied. Metallic ion release from the different alloys was
      analysed in a saliva environment at 37 degrees C. The nickel-chromium alloy
      exhibited important corrosion and a high quantity of ions was released. The
      titanium presented a low value of ion release and a good corrosion resistance due
      to the passive film on the metal surface. The high gold content alloy provided
      the best corrosion resistance.

PMID- 10907436
TI  - [Pulmonary embolism at the dawn of the year 2000].

PMID- 10907437
TI  - [Physiopathology of pulmonary arterial hypertension and gas exchange in acute
      pulmonary embolism].
AB  - Pulmonary embolism alters the distribution of ventilation/perfusion
      relationships, and increases pulmonary vascular resistance. These changes lead to
      hypoxemia and hypocapnia, and eventually, to right heart failure. The thin-walled
      and compliant right ventricle adapts to any increase in afterload by dilatation
      and decreased stroke volume, but this is largely prevented or delayed by the
      pulmonary circulation being a low resistance, recruitable and distensible
      circuit. Pulmonary embolism cannot be associated with a mean pulmonary artery
      pressure higher than 40 mmHg. More severe pulmonary hypertension indicates the
      presence of a hypertrophied right ventricle in the context of preexistent cardiac
      or pulmonary disease. Gas exchange is initially affected because of increased
      ventilation/perfusion ratios in embolized lung areas, and decreased
      ventilation/perfusion ratios in remaining non embolized lung areas. Both
      physiologic shunt and physiologic dead space increase accordingly, resulting in
      hypoxemia and hypocapnia. However, these changes are rapidly affected by an
      increase in ventilation, and by a "pneumoconstriction" which decreases
      physiologic dead space in embolized areas. In addition, a series of secondary
      alterations contribute to increase perfusion to lung units with low
      ventilation/perfusion ratios, thereby aggravating hypoxemia, while hypocapnia
      persists.

PMID- 10907438
TI  - [The value of biological and clinical signs of pulmonary embolism].
AB  - Pulmonary embolism (PE) is often underdiagnosed, mainly because it is not thought
      of. Its clinical signs are not highly specific and are encountered in a wide
      range of pulmonary diseases. Certain symptoms and signs, particularly when
      combined, are suggestive of PE: unexplained dyspnea, pleuretic pain with or
      without hemoptysis, tachypnea, etc. but they are not pathognomonic. Routine
      laboratory investigations such as arterial blood gas analysis, total blood cell
      count, serum LDH, etc. ... contribute poorly to making the diagnosis. D-dimers
      are fibrin degradation products. It has now been made possible to rule out PE in
      almost 20% of suspected cases, when plasma D-dimers levels are lower than 500
      ng/ml, using the ELISA technique, with a very high sensitivity rate (98%). On the
      other hand, their specificity and positive predictive value are low (< 50%) and
      under no circumstances should their measurement be used to confirm the diagnosis
      of PE. This test is time-consuming, but new faster techniques seem to be
      promising.

PMID- 10907439
TI  - [Radioisotopic studies and pulmonary thromboembolic diseases].
AB  - Perfusion and ventilation-perfusion lung scans are widely used as pivotal tests
      in the diagnostic work-up of patients with clinically suspected pulmonary
      embolism. Lung scan is a safe and reliable non invasive method to evaluate
      pulmonary blood flow restoration after an acute pulmonary embolism. The follow-up
      lung scan performed at completion of anticoagulant therapy serves as a new
      baseline for the diagnosis of recurrent pulmonary embolism.

PMID- 10907440
TI  - [The respective role and limitations of pulmonary angiography, thoracic computed
      tomography, and MRI in the diagnosis of pulmonary embolism].
AB  - Spiral or helical angioscanography for the positive or differential diagnosis of
      pulmonary emboli has become an emerging technique but remains poorly practised
      and has been little assessed scientifically. The optimal conditions to perform
      the test should be understood. The physician should appreciate in view of a large
      choice of parameters, the diagnostic value of the result and its reliability
      proximally and distally. Pulmonary angiography is only indicated when the
      angioscanography is negative according to the degree of clinical and paraclinical
      suspicion. Angiography magnetic resonance imaging is a diagnostic test full of
      promise which does not yet have its place in routine practice.

PMID- 10907442
TI  - [Diagnostic strategies for pulmonary embolism and decision analysis].
AB  - Decision analysis has greatly benefited to the field of pulmonary embolism
      diagnosis, by allowing the theoretical assessment of potential novel strategies,
      which could in turn be validated in clinical trials. The adjunction of clinical
      probability assessment, plasma D-dimer measurement, and lower limb venous
      compression ultrasonography, to pulmonary scintigraphy and angiography in the
      diagnostic workup, results in a considerable reduction in the requirement for
      angiography. Moreover, these strategies are highly cost-effective, yielding cost
      savings without increasing morbidity or mortality. Such diagnostic algorithms are
      safe, as demonstrated by clinical outcome studies. Finally, spiral CTscan
      combined with D-dimer and ultrasonography could also prove highly cost-effective,
      and replace either pulmonary angiography, or even both lung scan and angiography,
      if ongoing studies confirm the promising preliminary results obtained with
      CTscan. However, such a conclusion awaits the validation of algorithms including
      CTscan by clinical outcome trials, in which the therapeutic decision would rest
      on the result of the spiral CTscan.

PMID- 10907441
TI  - [Pulmonary embolism: the techniques, indications and diagnostic impact of lower
      limb investigations].
AB  - The non-invasive diagnosis of pulmonary emboli is based, in part, on evidencing a
      deep venous thrombosis (TVP-DVT); one of the principal features of thromboembolic
      disease with pulmonary emboli. Ultrasonic venograms have been introduced as the
      best non-invasive morphological examination for the diagnosis of DVT. Its
      sensitivity in subjects suspected of having pulmonary emboli (but having no frank
      signs of DVT) is inferior to that observed in cases where there is a clinical
      suspicion of DVT. On the other hand, only 70 per cent of subjects having
      pulmonary emboli have a DVT of the lower limbs on phlebography. For these
      reasons, only a positive ultrasonogram has any value in the diagnostic process as
      a negative ultrasonic venogram does not allow a pulmonary embolus to be excluded
      with certainty. A search for a DVT of the lower limbs should thus be integrated
      into the diagnostic approach which is both reasoned and rigorous in a search for
      pulmonary emboli.

PMID- 10907443
TI  - [Strategies for prevention of pulmonary embolism during at-risk surgeries and in
      the medical environment].
AB  - Pulmonary embolus is a significant aspect of thromboembolic venous disease which
      globally is the third most important cardiovascular disorder. There are several
      methods of primary prevention to decrease morbidity and mortality related to this
      disease. This article consists of a review of the most current methods of
      prophylaxis followed by practical recommendations for surgical, medical and
      obstetric patients.

PMID- 10907444
TI  - [Strategies for utilization of anticoagulants in pulmonary embolism].
AB  - Anticoagulant therapy significantly reduces the incidence of fatal recurrent
      thromboembolism and mortality. Today, initial anticoagulant therapy in acute
      pulmonary embolism mostly consists in the use of intravenous non fractioned
      heparin associated with simultaneous oral anticoagulation. Treatment with non
      fractioned heparin is continued until the INR is between 2 and 3 for 2
      consecutive days. Long term therapy with antivitamin K should be continued for at
      least 3 months. It is recommended that patients with recurrent venous
      thromboembolism should be treated indefinitively. Long term anticoagulant therapy
      will be discussed individually in the presence of a persistent risk factor. Low
      molecular weight heparins have been evaluated in the initial treatment of
      patients with acute, hemodynamically stable pulmonary embolism and are as
      effective and safe as continuous intravenous non fractioned heparin. Low
      molecular weight heparins will probably replace non fractioned heparin in the
      initial treatment of acute hemodynamically stable pulmonary embolism, on a short
      term perspective.

PMID- 10907446
TI  - [Inferior vena cava interruption. How and when?].
AB  - Caval interruption has been, historically, the first "treatment" of venous
      thromboembolic disease. Following ligation, plication, then clips, and finally
      intracaval filters constituted the successive improvements of this procedure,
      which can now be considered reasonably safe. However, reliable and clinically
      relevant data regarding long-term safety are lacking; recent data suggest that
      caval filters might increase the risk of recurrent deep venous thrombosis. As
      almost no controlled trials are available, indications for caval interruption are
      based on fragile grounds: contraindications to and failure of anticoagulant
      treatment in patients with recent proximal deep venous thrombosis remain the only
      two widely accepted indications. Although the PREPIC study, first prospective
      controlled trial on caval filters, confirmed their efficacy for preventing
      pulmonary embolism, the addition of caval filters to preventive or curative
      anticoagulant treatment in high-risk patients is still a matter of debate,
      because "very high-risk" settings despite anticoagulant treatment remain poorly
      defined. Finally, the risk-benefit ratio of caval interruption in addition to
      medical thrombolysis, or as an alternative to preventive or curative
      anticoagulant treatment appears unfavorable. The relevance of debatable
      indications, the precise identification of "very high-risk" patients, and the
      determination of the "best" filter should be assessed in specific prospective
      clinical trials.

PMID- 10907445
TI  - [Diagnosis and development of heparin-induced thrombocytopenia. Biological and
      clinical aspects].
AB  - Two types of thrombocytopenia occur during treatment with heparin: type I and
      type II heparin-induced thrombocytopenia (HIT). Type I HIT is due to a direct
      interaction between heparin and platelets. They are asymptomatic, occur early,
      mild and transitory. Type II HIT which is immunoallergic in nature is the most
      important complication of this treatment. The thrombocytopenia has a different
      presentation, acute with a fall in platelets over 30 per cent and is often
      associated with the occurrence or worsening of a venous or arterial thrombotic
      episode. The major problems of this secondary type are threefold: its
      recognition, its confirmation and its management should be as early as possible
      to avoid the development of often dramatic complications which compromise the
      prognosis. Laboratory investigations are required by highly reliable specialist
      laboratories following a careful clinical history. The natural history of the
      platelet count should enable the difficult diagnosis of HIT to be made more
      accurately. The treatment of confirmed HIT and/or symptomatic HIT often requires
      a multidisciplinary approach from a specialized team involving clinicians and
      hematologists. Two therapies with the benefit of large experience have just been
      obtained in France with marketing approval (AMM) for the management of HIT:
      danaparoid (Orgaran) and recombinant hidurin, lepirudin (Refludan). A declaration
      to the regional drugs monitoring center should not be omitted. In addition, each
      patient should be given a certificate confirming the immunallergy thus avoiding
      any further exposure with potentially dramatic consequences.

PMID- 10907447
TI  - [New medical anticoagulants].
AB  - The limitations of conventional treatment using nonfractionated heparin have
      stimulated research in new anticoagulants which act at different levels of the
      coagulation pathways. New natural or synthetic compounds have been developed to
      improve current treatments. Included among these compounds are indirect thrombin
      inhibitors such as dermatan sulfate, heparanoids and low-molecular weight
      heparin. Low-molecular weight heparins are particularly interesting for venous
      thromboembolism and acute coronary syndromes. Several studies have demonstrated
      their efficacy in unstable angina and myocardial infarction without Q wave. In
      comparison with nonfractionated heparin, administration of enoxaparin offers a
      supplementary benefit. Indirect thrombin inhibitors such as hirudin and its
      derivatives are also being evaluated and have shown a certain efficacy in the
      prevention of postoperative deep vein thrombosis although no superior effect
      compared with nonfractionated heparin has been demonstrated in thrombotic
      coronary disease. Finally, indirect anti-Xa agents and physiological coagulation
      inhibitors are also being assessed.

PMID- 10907448
TI  - [Management of serious pulmonary embolism].
AB  - In-hospital mortality is high when pulmonary embolism is complicated by
      hemodynamic instability and/or pulmonary hypertension. Death occurs frequently
      within the first hours after admission. This implies specific diagnostic and
      therapeutic management. Spiral CT seems to be an excellent diagnostic procedure
      in this setting. However, pulmonary angiography and perfusion lung scan can also
      be employed. Cardiac echography can help in the diagnosis and therapeutic
      decision making. Supportive therapy mainly includes correction of hypovolemia if
      present, a limited volume loading in other cases, and the use of dobutamine.
      Norepinephrine is the drug of choice when hypotension is present. Thrombolytic
      agents are indicated in case of hemodynamic instability. Modalities of
      administration and contra indications are currently well established. Surgical
      embolectomy should be performed in cases of uncontrolled shock, when thrombolysis
      is contra-indicated or uneffective.

PMID- 10907449
TI  - [What investigations should be done following the first episode of pulmonary
      embolism?].
AB  - Thromboembolic venous disease is both common and potentially serious, thus the
      first episode of pulmonary embolus calls for careful assessment. This involves
      two stages: a search for a venous localization of the pulmonary embolus and a
      search for risk factors contributing to thromboembolic venous disease. The
      emergence of non-invasive echographic-Doppler techniques and echocardiography
      make possible the localization of any residual venous thrombus. The risk of post
      thrombotic disease is raised in symptomatic thrombotic venous disease which
      requires wearing elastic stockings for a least two years. On the other hand this
      risk has not been assessed in asymptomatic cases of venous thrombosis. A search
      for risk factors requires a detailed history, a rigorous clinical examination and
      a routine list of laboratory investigations. Some complex investigations for
      detecting the early stages of a neoplasm would not appear justified unless there
      is objective evidence to support his. At the same time thrombophilia studies are
      not currently performed routinely for a first episode but may be suggested in the
      following cases: family history of thromboembolic venous disease, age less than
      45, including those in whom the episode occurs at the same time as pregnancy, or
      whilst taking hormone therapy, idiopathic thromboembolism, the association of
      arterial and venous thrombi and finally venous thromboses occurring in an unusual
      anatomical site. Prospective studies have shown the value of long term
      anticoagulation in patients suffering from constitutional hemostatic anomalies.
      Finally, if there is an after thought of occult cancer or constitutional
      thrombocytopenia a careful follow up should be performed particularly during the
      first year.

PMID- 10907450
TI  - [What etiologic investigations should be done following recurrent pulmonary
      embolism?].
AB  - Recurrence of pulmonary embolism can occur in presence of coagulation disorders
      or cancer. It can also develop without any of these factors. Coagulation tests
      should search for abnormalities such as inherited deficiencies of antithrombin,
      protein C, protein S, factor V mutation, variation of the prothrombin gene,
      hyperhomocysteinaemia, lupus anticoagulant, antiphospholipid antibodies.
      Biological examinations for determining the cause of recurrent pulmonary should
      be associated with a familial enquiry. An aggressive search for an occult cancer
      in a patient with a recurrent pulmonary embolism is not warranted. An evaluation
      includes medical history, physical examination, laboratory tests, chest X-ray
      sufficient to orientate this investigation. Patients should be given long-course
      oral anticoagulant treatment. However, the optimal duration have still to be
      determined.

PMID- 10907451
TI  - [Chronic thromboembolic pulmonary arterial hypertension].
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon disease with
      a severe prognosis. Initially considered as a constantly fatal disease, it can be
      cured since the advent in the late 80's of thromboendarterectomy. CTEPH occurs in
      approximately 0.1% of patients who survive acute pulmonary embolism. Such outcome
      is due to the failure of the normal thrombi resolution in the pulmonary
      circulation. This disease is observed in both sexes and occasionally as early as
      in the third decade. Many patients have no history of acute venous
      thromboembolism which is responsible for the frequent diagnosis delay. Therefore,
      it is of paramount importance to search for pulmonary vascular disease when
      patients complain solely of dyspnea on exertion. These patients should undergo
      echocardiography and, if necessary, right heart catheterization. Once the
      diagnosis of pulmonary hypertension is established the next step is to find the
      cause. Ventilation-perfusion scanning is probably the most sensitive non-invasive
      test to provide evidence that pulmonary hypertension is related to chronic
      thromboembolism. Angiography and helical computed tomography allow to confirm the
      diagnosis of CTEPH and to determine whether it is accessible or not to
      thromboendarterectomy. Most patients who undergo thromboendarterectomy improve
      clinically and in terms of gas exchange and pulmonary hemodynamics. When thrombi
      are inaccessible surgically, patients should be placed on the list for lung
      transplantation if they fulfill the criteria established for primary pulmonary
      hypertension. When all surgical procedures are contraindicated, anticoagulant and
      oxygen therapy remain the sole possibility of treatment.

PMID- 10907452
TI  - [Pulmonary embolism and pregnancy].
AB  - Pulmonary emboli are frequent during pregnancy and the post partum period and
      represent one of the major causes of maternal mortality during this period. It is
      estimated that there is an increased risk of thromboembolic venous disease during
      pregnancy at 1:1000 to 1:2000 pregnancies. This is explained by changes in the
      physiology and biology of coagulation factors and fibrinolysis. The risk is
      increased in those aged more than 35, the presence of a past history of
      thromboembolic venous disease; hereditary or acquired thrombophilia or delivery
      by caesarean section. The diagnosis should be confirmed with the same rigor as
      outside pregnancy. No diagnostic examination is contraindicated in those pregnant
      but the diagnostic strategy should be in favor of non-invasive examinations with
      ultrasonic venography of the lower limbs and/or pulmonary scintigraphy being the
      investigations of choice. The treatment of pulmonary emboli during pregnancy
      rests on heparin, coumarin being strictly contraindicated due to the risk of
      fetal malformation. Low molecular weight heparin is not currently used during
      pregnancy but initial data in the literature suggests that they may be used
      during pregnancy without increased risk compared to non-fractionated heparin. The
      indications for anticoagulant prophylaxis remains poorly characterized.

PMID- 10907453
TI  - Emergence of the haematopoietic system in the human embryo and foetus.

PMID- 10907454
TI  - Characterisation and biology of normal human haematopoietic stem cells.

PMID- 10907455
TI  - Gene regulation in normal and leukaemic progenitor/stem cells.

PMID- 10907457
TI  - Monoclonal antibodies in the treatment of non-Hodgkin's lymphoma patients.

PMID- 10907456
TI  - DNA vaccines against haematological malignancies.
AB  - DNA vaccines against cancer have to activate an inadequate or damaged immune
      system in order to attack residual cancer cells. Although the potential problem
      of tolerance may be overcome by transplantation, provision of high levels of T
      cell help is likely to be an important factor in stimulating effective immune
      pathways. The fusion gene approach appears to provide the required help, and
      offers a rational design for raising both antibody and T-cell mediated attack
      against lymphoma and myeloma, which express idiotypic antigen at the cell surface
      or as a secreted protein respectively. Intriguingly, preliminary data indicate
      that the fusion gene approach promotes antibody responses against a different
      cell surface tumour antigen, CEA. Strategies for using DNA vaccines to induce
      attack on processed peptides bound to MHC class I molecules are also being
      developed. We hope and anticipate that all categories of tumour antigen may be
      susceptible to this powerful new technology. The critical clinical requirement,
      however, will be to treat the presenting tumour with maintenance or restoration
      of immune capacity. We await results of the preliminary clinical trials with
      great interest.

PMID- 10907458
TI  - Antisense oligonucleotides for haematological malignancies.

PMID- 10907459
TI  - Dendritic cell maturation and generation of immune responses.

PMID- 10907460
TI  - Cytotoxic T lymphocyte priming versus cytotoxic T lymphocyte tolerance induction:
      a delicate balancing act involving dendritic cells.

PMID- 10907461
TI  - The role of chemokines and chemokine receptors in T cell priming and Th1/Th2
      mediated responses.

PMID- 10907462
TI  - Autoimmune thrombophilic syndromes.

PMID- 10907464
TI  - Hepatic veno-occlusive disease following peripheral blood stem cell or bone
      marrow transplantation.

PMID- 10907463
TI  - The pathogenesis and management of essential thrombocythaemia.

PMID- 10907465
TI  - Donor selection-matching for mismatches.

PMID- 10907466
TI  - Cytomegalovirus infection following stem cell transplantation.

PMID- 10907467
TI  - Improved results in marrow transplantation from unrelated donors. Genoa BMT
      Group.

PMID- 10907469
TI  - Homocysteine and ischaemic heart disease.

PMID- 10907468
TI  - Homocysteine, folate enzymes and neural tube defects.

PMID- 10907471
TI  - Transgenic models of T-cell prolymphocytic leukaemia.

PMID- 10907470
TI  - Homocysteine, platelet function and thrombosis.

PMID- 10907472
TI  - A murine transgenic model of human cold agglutinin disease.

PMID- 10907473
TI  - The APL-associated fusion proteins.

PMID- 10907474
TI  - Diagnosis, front line treatment and molecular monitoring of acute promyelocytic
      leukaemia.

PMID- 10907475
TI  - Arsenicals and inhibitors of histone deacetylase as anticancer therapy.

PMID- 10907476
TI  - Requirements for appropriate evaluation of diagnostic tests in suspected
      pulmonary embolism.

PMID- 10907477
TI  - Clinical significance of non clinical end-points in studies on the prevention of
      venous thromboembolism.

PMID- 10907478
TI  - Randomised evaluation of treatment modalities in thromboembolic disorders.

PMID- 10907479
TI  - Cytogenetics and molecular genetics of chronic lymphocytic leukaemia.

PMID- 10907480
TI  - Morphology, atypical chronic lymphocytic leukaemia and prognostic features
      affecting choice of therapy.

PMID- 10907481
TI  - Chronic lymphocytic leukaemia. Current strategy and new perspectives of
      treatment.

PMID- 10907483
TI  - Metaphase FISH, microdissection, and multicolour FISH. Applications in
      haematology.

PMID- 10907482
TI  - Prognostic factors in chronic lymphocytic leukaemia.

PMID- 10907484
TI  - Interphase FISH in chronic lymphoproliferative disorders and comparative genomic
      hybridisation in the study of lymphomas.

PMID- 10907485
TI  - Detection of recurrent translocations using real time PCR; assessment of the
      technique for diagnosis and detection of minimal residual disease.

PMID- 10907486
TI  - Neonatal alloimmune thrombocytopenia.

PMID- 10907487
TI  - Potential and current development of platelet products.

PMID- 10907488
TI  - Current status of non-transfusional haemostatic agents.

PMID- 10907489
TI  - Expert Consensus Guideline Series: Treatment of psychiatric and behavioral
      problems in mental retardation.

PMID- 10907491
TI  - Arbeitsgemeinschaft Stabile Isotope 21st annual meeting. Gottingen, October 4-6,
      1999. Abstracts.

PMID- 10907492
TI  - Advances in gene technology: DNA, RNA and Cancer. Miami Bio/Technology Winter
      Symposium. February 5-9, 2000. Abstracts.

PMID- 10907493
TI  - [VIII Congress of the Spanish Society of Neuroscience. Murcia, Spain, 25-29
      September 1999. Abstracts].

PMID- 10907494
TI  - Naphthalene endoperoxides as generators of singlet oxygen in biological media.

PMID- 10907495
TI  - Photosensitized production of singlet oxygen.
AB  - Photosensitization is a simple and controllable method for the generation of
      singlet oxygen in solution and in cells. Methods are described for determining
      the yield of singlet oxygen in solution, for measurement of the rate of reaction
      between singlet oxygen and a substrate, and for comparing the effectiveness of
      singlet oxygen generated by different photosensitizers in cells. These
      quantitative measurements can lead to better understanding of the interaction of
      singlet oxygen with biomolecules.

PMID- 10907496
TI  - Singlet oxygen from irradiated titanium dioxide and zinc oxide.

PMID- 10907497
TI  - Time-resolved singlet oxygen detection.

PMID- 10907498
TI  - Measurement of photogenerated singlet oxygen in aqueous media.

PMID- 10907499
TI  - Assay for singlet-oxygen generation by peroxidases using 1270-nm
      chemiluminescence.

PMID- 10907500
TI  - Formation of electronically excited states during the oxidation of arachidonic
      acid by prostaglandin endoperoxide synthase.

PMID- 10907501
TI  - Singlet oxygen detection with sterically hindered amine derivatives in plants
      under light stress.

PMID- 10907503
TI  - Singlet oxygen scavenging in phospholipid membranes.

PMID- 10907502
TI  - Cholesterol as a singlet oxygen detector in biological systems.
AB  - In cells under oxidative attack, membrane Ch, through the formation of its
      signature hydroperoxide and diol products, can serve as a unique detector in
      situ, allowing discrimination between 1O2 and free radical intermediacy. Of the
      two techniques described for analyzing Ch oxidation products, TLC with color
      development suffices for preliminary, mainly qualitative product screening,
      whereas a high-performance approach such as HPLC-EC(Hg) is advised when maximum
      resolution and sensitivity of quantitation are necessary. By using these
      strategies, one can monitor the formation of 1O2, for example, in a biologically
      relevant milieu (membrane), thus avoiding the difficulties associated with
      external detection, e.g., by physical means. These approaches would be valuable
      for assessing reaction mechanisms for various oxidative agents of biomedical
      importance, including environmental phototoxins and the rapidly emerging family
      of phototherapeutic drugs. Although photodynamic stress has been emphasized, the
      methods described should have broad applicability in the elucidation of oxidative
      mechanisms.

PMID- 10907504
TI  - Catalase modification as a marker for singlet oxygen.

PMID- 10907505
TI  - Nuclear factor-kappa B activation by singlet oxygen produced during
      photosensitization.

PMID- 10907506
TI  - Mitogen-activated protein kinase activation by singlet oxygen and ultraviolet A.

PMID- 10907507
TI  - Singlet oxygen DNA damage products: formation and measurement.

PMID- 10907508
TI  - Ultraviolet A- and singlet oxygen-induced mutation spectra.

PMID- 10907509
TI  - Damage to DNA by long-range charge transport.

PMID- 10907510
TI  - Cholesterol photodynamic oxidation by ultraviolet irradiation and cholesterol
      ozonization by ozone exposure.

PMID- 10907511
TI  - Bactericidal and virucidal activities of singlet oxygen generated by thermolysis
      of naphthalene endoperoxides.

PMID- 10907512
TI  - Inactivation of viruses in human plasma.

PMID- 10907513
TI  - 3-(4'-methyl-1'-naphthyl)propionic acid, 1',4'-endoperoxide for dioxygenation of
      squalene and for bacterial killing.

PMID- 10907514
TI  - Biological singlet oxygen quenchers assessed by monomol light emission.

PMID- 10907515
TI  - Synthetic singlet oxygen quenchers.

PMID- 10907516
TI  - Dosimetry of ultraviolet A radiation.

PMID- 10907518
TI  - Signaling pathways leading to nuclear factor-kappa B activation.

PMID- 10907517
TI  - Radiation-induced signal transduction.

PMID- 10907519
TI  - Gene regulation by ultraviolet A radiation and singlet oxygen.

PMID- 10907520
TI  - Role for singlet oxygen in biological effects of ultraviolet A radiation.

PMID- 10907521
TI  - Ultraviolet A-1 irradiation as a tool to study the pathogenesis of atopic
      dermatitis.

PMID- 10907522
TI  - Ultraviolet A radiation-induced apoptosis.

PMID- 10907523
TI  - Singlet oxygen-triggered immediate preprogrammed apoptosis.

PMID- 10907524
TI  - Determination of DNA damage, peroxide generation, mitochondrial membrane
      potential, and caspase-3 activity during ultraviolet A-induced apoptosis.

PMID- 10907525
TI  - Mechanism of photodynamic therapy-induced cell death.

PMID- 10907526
TI  - Photocarcinogenesis: UVA vs UVB.
AB  - Ultraviolet B and A radiations (respective wavelength ranges 280-315 and 315-400
      nm) are present in sunlight at ground level. The ultraviolet radiation does not
      penetrate any deeper than the skin and has been associated with various types of
      human skin cancers. The carcinogenicity of UVB radiation is well established
      experimentally and, to a large extent, understood as a process of direct
      photochemical damage to DNA from which gene mutations arise. Although UVA is
      generally far less carcinogenic than UVB radiation, it is present more abundantly
      in sunlight than UVB radiation (> 20 times radiant energy) and can, therefore,
      contribute appreciably to the carcinogenicity of sunlight. In contrast to UVB,
      UVA radiation is hardly absorbed by DNA. Hence, the absorption by other molecules
      (endogenous photosensitizers) becomes more important, thus radicals and, more
      specifically, reactive oxygen species can be generated that can damage DNA,
      membranes, and other cellular constituents. These photochemical differences
      between UVA and UVB radiations are reflected in differences in cellular responses
      and carcinogenesis.

PMID- 10907527
TI  - Photoaging-associated large-scale deletions of mitochondrial DNA.
AB  - Heteroplasmy, replicative segregation, low copy numbers of mtDNA, and selection
      mechanisms at the molecular and cellular level are all factors that determine
      requirements toward the experimental design for the detection and the
      quantification of mtDNA mutations. The short half-life and low stability of ROS
      further increase the technical demands. However, the continuous improvement of
      techniques has given us more insight into the interactions between ROS and mtDNA,
      both at the level of endogenous ROS produced by the normal mitochondrial
      metabolism and exogenous sources of ROS, such as singlet oxygen, which can result
      from treatments such as UVA exposure.

PMID- 10907528
TI  - Role of activated oxygen species in photodynamic therapy.

PMID- 10907529
TI  - Gas chromatography-mass spectrometry analysis of DNA: optimization of protocols
      for isolation and analysis of DNA from human blood.

PMID- 10907530
TI  - Sequence specificity of ultraviolet A-induced DNA damage in the presence of
      photosensitizer.

PMID- 10907531
TI  - Protein oxidative damage.

PMID- 10907532
TI  - DNA damage induced by ultraviolet and visible light and its wavelength
      dependence.

PMID- 10907533
TI  - Photoprotection of skin against ultraviolet A damage.

PMID- 10907534
TI  - Topically applied antioxidants in skin protection.

PMID- 10907535
TI  - Erythropoietic protoporphyria: treatment with antioxidants and potential cure
      with gene therapy.

PMID- 10907536
TI  - Porphyrias: photosensitivity and phototherapy.

PMID- 10907537
TI  - Carotenoids in human skin: noninvasive measurement and identification of dermal
      carotenoids and carotenol esters.

PMID- 10907538
TI  - Reactive absorption of ozone: an assay for reaction rates of ozone with
      sulfhydryl compounds and with other biological molecules.

PMID- 10907539
TI  - Assay for singlet oxygen generation by plant leaves exposed to ozone.

PMID- 10907540
TI  - Ozone effects on plant defense.

PMID- 10907541
TI  - High-pressure liquid chromatography analysis of ozone-induced depletion of
      hydrophilic and lipophilic antioxidants in murine skin.

PMID- 10907542
TI  - Reactions of vitamin E with ozone.

PMID- 10907543
TI  - Induction of nuclear factor-kappa B by exposure to ozone and inhibition by
      glucocorticoids.

PMID- 10907544
TI  - Detection of 4-hydroxy-2-nonenol adducts following lipid peroxidation from ozone
      exposure.

PMID- 10907545
TI  - Synthesis of inflammatory signal transduction species formed during ozonation
      and/or peroxidation of tissue lipids.

PMID- 10907546
TI  - Assay for redox-sensitive transcription factor.

PMID- 10907547
TI  - Fluorescent fatty acid to monitor reactive oxygen in single cells.

PMID- 10907548
TI  - Noninvasive techniques for measuring oxidation products on the surface of human
      skin.

PMID- 10907549
TI  - The molecular genetics of cultivated mushrooms.
AB  - The types, economic significance and methods of production of the principal
      cultivated mushrooms are described in outline. These organisms are all less than
      ideal for conventional genetic analysis and breeding, so molecular methods afford
      a particular opportunity to advance our understanding of their biology and
      potentially give the prospect of improvement by gene manipulation. The sequences
      described are limited to those found in GenBank by August 1999. The gene
      sequences isolated from the white button mushroom Agaricus bisporus, the shiitake
      Lentinula edodes, the oyster mushrooms Pleurotus spp., the paddy straw mushroom
      Volvariella volvacea and the enotake Flammulina velutipes are described. The
      largest group are genes from A. bisporus, which includes 29 for intracellular
      proteins and 12 for secreted proteins. In comparison, only a total of 26
      sequences can be reported for the other cultivated species. A. bisporus is also
      the only cultivated species for which molecular karyotyping is already supported
      by reliable markers for all 13 of its chromosomes.

PMID- 10907550
TI  - The intestinal microflora: potentially fertile ground for microbial
      physiologists.
AB  - The intestinal microflora provides opportunities for microbial physiological
      research. The metabolic interactions of bacterial inhabitants of the intestinal
      community, bacterial bioenergetics, preferential utilization of substrates as
      energy sources by specific bacterial species, and intercellular signalling are
      among the topics of challenging research awaiting the attention of microbial
      physiologists.

PMID- 10907551
TI  - Primary metabolism and its control in streptomycetes: a most unusual group of
      bacteria.
AB  - Streptomycetes are Gram-positive bacteria with a unique capacity for the
      production of a multitude of varied and complex secondary metabolites. They also
      have a complex life cycle including differentiation into at least three distinct
      cell types. Whilst much attention has been paid to the pathways and regulation of
      secondary metabolism, less has been paid to the pathways and the regulation of
      primary metabolism, which supplies the precursors. With the imminent completion
      of the total genome sequence of Streptomyces coelicolor A3(2), we need to
      understand the pathways of primary metabolism if we are to understand the role of
      newly discovered genes. This review is written as a contribution to supplying
      these wants. Streptomycetes inhabit soil, which, because of the high numbers of
      microbial competitors, is an oligotrophic environment. Soil nutrient levels
      reflect the fact that plant-derived material is the main nutrient input; i.e. it
      is carbon-rich and nitrogen- and phosphate-poor. Control of streptomycete primary
      metabolism reflects the nutrient availability. The variety and multiplicity of
      carbohydrate catabolic pathways reflects the variety and multiplicity of
      carbohydrates in the soil. This multiplicity of pathways has led to investment by
      streptomycetes in pathway-specific and global regulatory networks such as glucose
      repression. The mechanism of glucose repression is clearly different from that in
      other bacteria. Streptomycetes feed by secreting complexes of extracellular
      enzymes that break down plant cell walls to release nutrients. The induction of
      these enzyme complexes is often coordinated by inducers that bear no structural
      relation to the substrate or product of any particular enzyme in the complex;
      e.g. a product of xylan breakdown may induce cellulase production. Control of
      amino acid catabolism reflects the relative absence of nitrogen catabolites in
      soil. The cognate amino acid induces about half of the catabolic pathways and
      half are constitutive. There are reduced instances of global carbon and nitrogen
      catabolite control of amino acid catabolism, which again presumably reflects the
      relative rarity of the catabolites. There are few examples of feedback repression
      of amino acid biosynthesis. Again this is taken as a reflection of the
      oligotrophic nature of the streptomycete ecological niche. As amino acids are not
      present in the environment, streptomycetes have rarely invested in feedback
      repression. Exceptions to this generalization are the arginine and branched-chain
      amino acid pathways and some parts of the aromatic amino acid pathways which have
      regulatory systems similar to Escherichia coli and Bacillus subtilis and other
      copiotrophic bacteria.

PMID- 10907552
TI  - Adaptation of oral streptococci to low pH.
AB  - The strategies employed by oral streptococci to resist the inimical influences of
      acidification reflect the diverse and dynamic niches of the human mouth. All of
      the oral streptococci are capable of rapid degradation of sugar to acidic end
      products. As a result, the pH value of their immediate environment can plummet to
      levels where glycolysis and growth cease. At this point, the approaches for
      survival in acid separate the organisms. Streptococcus mutans, for example,
      relies on its F-ATPase, to protect itself from acidification by pumping protons
      out of the cells. S. salivarius responds by degrading urea to ammonia and S.
      sanguis produces ammonia by arginolysis. The mechanisms by which these organisms
      regulate their particular escape route are now being explored experimentally. The
      picture that emerges is that the acid-adaptive regulatory mechanisms of the oral
      streptococci differ markedly from those employed by Gram-negative bacteria. What
      remains to be elucidated are the breadth of the acid-response systems in these
      organisms and how they permit the microbes to sustain themselves in the face of
      low pH and the bacterial competition present in their respective niches. In this
      article, we summarize reports concerning the means by which oral streptococci
      either utilize acidification to subdue their competitors or protect themselves
      until pH values return to a more favorable level.

PMID- 10907553
TI  - Metal ion transport in eukaryotic microorganisms: insights from Saccharomyces
      cerevisiae.
AB  - Metal ions such as iron, copper, manganese, and zinc are essential nutrients for
      all eukaryotic microorganisms. Therefore, these organisms possess efficient
      uptake mechanisms to obtain these nutrients from their extracellular environment.
      Metal ions must also be transported into intracellular organelles where they
      function as catalytic and structural cofactors for compartmentalized enzymes.
      Thus, intracellular transport mechanisms are also present. When present in high
      levels, metal ions can also be toxic, so their uptake and intracellular transport
      is tightly regulated at both transcriptional and post-transcriptional levels to
      limit metal ion overaccumulation and facilitate storage and sequestration.
      Remarkable molecular insight into these processes has come from recent studies of
      the yeast Saccharomyces cerevisiae. This organism, which is the primary subject
      of this chapter, serves as a useful paradigm to understand metal ion metabolism
      in other eukaryotic microbes.

PMID- 10907554
TI  - Iron uptake by fungi: contrasted mechanisms with internal or external reduction.
AB  - Almost all iron uptake by fungi involves reduction from Fe(III) to Fe(II) in
      order to facilitate ligand exchange. This leads to two mechanisms: uptake before
      reduction, or reduction before uptake. Many fungi secrete specific hydroxamate
      siderophores when short of iron. The mechanism with uptake before reduction is
      described in the context of siderophore synthesis and usage, since it applies to
      many (but not all) siderophores. The hydroxamate functional group is synthesized
      from ornithine by N5 hydroxylation and acylation. In most fungal siderophores,
      two or three modified ornithines are joined together by a non-ribosomal peptide
      synthetase. The transcription of these genes is regulated by an iron activated
      repressor. There is evidence that the iron-free siderophore may be stored in
      intracellular vesicles until secretion is required. After loading with iron, re
      entry is likely to be via a proton symport. In some fungi, siderophores are used
      for iron storage. The iron is liberated by an NADPH-linked reductase. The second
      mechanism starts with Fe(III) reduction. In yeast, this is catalysed by an NADPH
      linked transmembrane reductase, which has homology with the NADPH oxidase of
      neutrophils. There are two closely similar reductases with overlapping roles in
      Fe(III) and Cu(II) reduction, while the substrates for reduction include Fe(III)
      siderophores. External reductants, which may be important in certain fungi,
      include 3-hydroxyanthranilic acid, melanin, cellobiose dehydrogenase and 2,5
      dimethylhydroquinone. In yeast, a high-affinity iron uptake pathway involves
      reoxidation of Fe(II) to Fe(III), probably to confer specificity for iron. This
      is catalysed by a copper protein which has homology with ceruloplasmin, and is
      closely coupled to Fe(III) transport. The transcription of these genes is
      regulated by an iron-inhibited activator. Because of its copper requirement, the
      high-affinity pathway is blocked by disruption of genes for copper metabolism. A
      low-affinity uptake transports Fe(II) directly and is important in anoxic growth.
      In many fungi, mechanisms with internal or external reduction are both important.
      The external reduction is applicable to almost any Fe(III) complex, while
      internal reduction is more efficient at low iron but requires a siderophore
      permease through which toxins might enter. Both mechanisms require close coupling
      of Fe(III) reduction and Fe(II) utilization in order to minimize production of
      active oxygen.

PMID- 10907555
TI  - Dynamics of metabolism and its interactions with gene expression during
      sporulation in Saccharomyces cerevisiae.
AB  - The dynamics of metabolism has been shown to be involved in the triggering of
      events that are concurrent with sporulation of the budding yeast Saccharomyces
      cerevisiae. Indeed, quantitative correlations have been demonstrated between
      sporulation and the rate of carbon substrate or oxygen consumption, and the
      fluxes through gluconeogenic and glyoxylate cycle pathways. The results suggest
      that an imbalance between catabolic and anabolic fluxes influences the occurrence
      of the differentiation process. The hypothesis that the initiation of sporulation
      is triggered by the accumulation of an intracellular metabolite is confronted
      with the notion that intermediary metabolism and the expression of genes involved
      in sporulation interact to trigger the differentiation process. Several pieces of
      evidence indicate that derepression of the gluconeogenic pathway is crucial for
      the initiation of sporulation. One of the possible pathways through which glucose
      repression hampers sporulation might be the repression of gluconeogenesis as well
      as that of respiratory activity, in turn modulating the expression of IMEL++. The
      stages defined in the dynamics of sporulating cultures, namely readiness and
      commitment, are related to metabolic events associated with sporulation. An
      interpretation in terms of metabolic flux dynamics is given to the reversal of
      commitment occurring when the normal progression to sporulation is somehow
      blocked. The quantitative data are here integrated in a model attempting to
      simulate the dynamics of metabolic as well as cellular events during sporulation.
      The model is envisaged as a test of the hypothesis that an imbalance between
      anabolism and catabolism is involved in initiation of the sporulation process. It
      is proposed that such an imbalance may be a signal for differential gene
      expression associated with the differentiation pathway.

PMID- 10907556
TI  - Carbon and nitrogen metabolism in Rhizobium.
AB  - One of the paradigms of symbiotic nitrogen fixation has been that bacteroids
      reduce N2 to ammonium and secrete it without assimilation into amino acids. This
      has recently been challenged by work with soybeans showing that only alanine is
      excreted in 15N2 labelling experiments. Work with peas shows that the bacteroid
      nitrogen secretion products during in vitro experiments depend on the
      experimental conditions. There is a mixed secretion of both ammonium and alanine
      depending critically on the concentration of bacteroids and ammonium
      concentration. The pathway of alanine synthesis has been shown to be via alanine
      dehydrogenase, and mutation of this enzyme indicates that in planta there is
      likely to be mixed secretion of ammonium and alanine. Alanine synthesis directly
      links carbon catabolism and nitrogen assimilation in the bacteroid. There is now
      overwhelming evidence that the principal carbon sources of bacteroids are the C4
      dicarboxylic acids. This is based on labelling and bacteroid respiration data,
      and mutation of both the dicarboxylic acid transport system (dct) and malic
      enzyme. L-malate is at a key bifurcation point in bacteroid metabolism, being
      oxidized to oxaloacetate and oxidatively decarboxylated to pyruvate. Pyruvate can
      be aminated to alanine or converted to acetyl-CoA where it either enters the TCA
      cycle by condensation with oxaloacetate or forms polyhydroxybutyrate (PHB). Thus
      regulation of carbon and nitrogen metabolism are strongly connected. Efficient
      catabolism of C4-dicarboxylates requires the balanced input and removal of
      intermediates from the TCA cycle. The TCA cycle in bacteroids may be limited by
      the redox state of NADH/NAD+ at the 2-ketoglutarate dehydrogenase complex, and a
      number of pathways may be involved in bypassing this block. These pathways
      include PHB synthesis, glutamate synthesis, glycogen synthesis, GABA shunt and
      glutamine cycling. Their operation may be critical in maintaining the optimum
      redox poise and carbon balance of the TCA cycle. They can also be considered to
      be overflow pathways since they act to remove or add electrons and carbon into
      the TCA cycle. Optimum operation of the TCA cycle has a major impact on nitrogen
      fixation.

PMID- 10907557
TI  - Redundancy of aerobic respiratory chains in bacteria? Routes, reasons and
      regulation.
AB  - Bacteria are the most remarkable organisms in the biosphere, surviving and
      growing in environments that support no other life forms. Underlying this ability
      is a flexible metabolism controlled by a multitude of environmental sensors and
      regulators of gene expression. It is not surprising, therefore, that bacterial
      respiration is complex and highly adaptable: virtually all bacteria have
      multiple, branched pathways for electron transfer from numerous low-potential
      reductants to several terminal electron acceptors. Such pathways, particularly
      those involved in anaerobic respiration, may involve periplasmic components, but
      the respiratory apparatus is largely membrane-bound and organized such that
      electron flow is coupled to proton (or sodium ion) transport, generating a
      protonmotive force. It has long been supposed that the multiplicity of pathways
      serves to provide flexibility in the face of environmental stresses, but the
      existence of apparently redundant pathways for electrons to a single acceptor,
      say dioxygen, is harder to explain. Clues have come from studying the expression
      of oxidases in response to growth conditions, the phenotypes of mutants lacking
      one or more oxidases, and biochemical characterization of individual oxidases.
      Terminal oxidases that share the essential properties of substrate (cytochrome c
      or quinol) oxidation, dioxygen reduction and, in some cases, proton
      translocation, differ in subunit architecture and complement of redox centres.
      Perhaps more significantly, they differ in their affinities for oxidant and
      reductant, mode of regulation, and inhibitor sensitivity; these differences to
      some extent rationalize the presence of multiple oxidases. However, intriguing
      requirements for particular functions in certain physiological functions remain
      unexplained. For example, a large body of evidence demonstrates that cytochrome
      bd is essential for growth and survival under certain conditions. In this review,
      the physiological basis of the many phenotypes of Cyd-mutants is explored,
      particularly the requirement for this oxidase in diazotrophy, growth at low
      protonmotive force, survival in the stationary phase, and resistance to oxidative
      stress and Fe(III) chelators.

PMID- 10907558
TI  - Training an adequate number of rural family physicians.

PMID- 10907559
TI  - Time to rethink continuity.

PMID- 10907560
TI  - Back to the drawing board.

PMID- 10907561
TI  - Singulair slam.

PMID- 10907562
TI  - Conflicting message in the title.

PMID- 10907563
TI  - Women family doctors. An emerging force in the 21st century.

PMID- 10907564
TI  - Antenatal phenobarbital for prevention of intraventricular hemorrhage in preterm
      infants.
AB  - QUESTION: One of my patients, a 36-year-old, who has had three pregnancies and
      two live births, delivered her third baby at 32 weeks' gestation. Her first
      pregnancy was complicated by premature labour, which led to delivery at 30 weeks'
      gestation. She received antenatal phenobarbital before the first delivery because
      it was considered proven therapy for preventing intraventricular hemorrhage in
      preterm infants. I would like to know why it is no longer routinely used. ANSWER:
      Cumulative results from recent studies have failed to confirm the initial
      impression of effectiveness of antenatal phenobarbital. It is no longer
      recommended when preterm delivery is anticipated.

PMID- 10907565
TI  - Ophthaproblem. Pseudophakic bullous keratopathy.

PMID- 10907566
TI  - Emergency case. Acute testicular pain.

PMID- 10907567
TI  - Bell's palsy: does anything help?

PMID- 10907568
TI  - Suspected ectopic pregnancy. Can it be predicted by history and examination?

PMID- 10907569
TI  - Palliative care on Manitoulin Island. Views of family caregivers in remote
      communities.
AB  - OBJECTIVE: To describe family caregivers' experiences with palliative care
      services in rural communities. DESIGN: Qualitative study. SETTING: Manitoulin
      Island, Ont. PARTICIPANTS: Thirteen family caregivers of 12 deceased patients who
      had received palliative care services. METHOD: Twenty-five family caregivers were
      recruited by mail and local newspaper. Eight were excluded because they lived off
      the Island or were too recently bereaved; one declined an interview; and three
      were excluded by researchers. Initial contact was by telephone; those retained
      (13 people) were interviewed at home. Interviews were conducted by the same
      researcher using a semistructured interview guide. All interviews were audiotaped
      and transcribed, and content was analyzed. MAIN FINDINGS: Three interwoven themes
      were identified: access to services, quality of services, and support and caring.
      Hospital and community-based services were accessed with ease at the local level;
      difficulties were noted when accessing services in tertiary care centres.
      Participants were generally grateful for and pleased with services received. Two
      areas of concern raised by participants were communication and pain and symptom
      control. Participants suggested to the Ministry of Health ways to improve rural
      palliative care services. More public funding for in-home palliative care
      services was identified as a priority. CONCLUSION: Participants thought good
      services and supportive care at the local level made up for difficulties in
      accessing and using palliative services in tertiary care centres. Community
      spirit and culture were seen as making situations more bearable.

PMID- 10907570
TI  - Short report: medical informatics. How do family medicine educators at McMaster
      University use it and teach it?

PMID- 10907571
TI  - Thrombolysis in the air. Air-ambulance paramedics flying to remote communities
      treat patients before hospitalization.
AB  - PROBLEM ADDRESSED: First Nations* communities in the North have a high prevalence
      of coronary artery disease and type 2 diabetes and face an increasing incidence
      of myocardial infarction (MI). Many conditions delay timely administration of
      thrombolysis, including long times between when patients first experience
      symptoms and when they present to community nursing stations, delays in air
      transfers to treating hospitals, uncertainty about when planes are available, and
      poor flying conditions. OBJECTIVE OF PROGRAM: To develop a program for
      administration of thrombolysis on the way to hospital by air ambulance paramedics
      flying to remote communities to provide more rapid thrombolytic therapy to
      northern patients experiencing acute MIs. COMPONENTS OF PROGRAM: Critical care
      flight paramedics fly to northern communities from Sioux Lookout, Ont; assess
      patients; communicate with base hospital physicians; review an exclusion criteria
      checklist; and administer thrombolytics according to the Sioux Lookout District
      Health Centre/Base Hospital Policy and Procedure Manual. Patients are then flown
      to hospitals in Sioux Lookout; Winnipeg, Man; or Thunder Bay, Ont. CONCLUSION:
      This thrombolysis program is being pilot tested, and further evaluation and
      development is anticipated.

PMID- 10907572
TI  - Identifying problem and compulsive gamblers.
AB  - OBJECTIVE: To present a meta-analysis of current research on the prevalence,
      identification, and treatment of problem and compulsive gamblers. QUALITY OF
      EVIDENCE: Problem and compulsive gambling was not a socio-scientific concern
      until the last two decades. Hence research on this topic is limited. The summary
      and analysis for this paper relied on computer searches of journal and news
      abstracts in addition to direct contact with organizations addressing the
      identification and treatment of compulsive gamblers. MAIN MESSAGE: An estimated
      5% of those who gamble run into problems. About 1% of those who gamble are
      predicted to experience serious problems. Successful treatment of problem and
      compulsive gambling continues to be a challenge. Although cognitive therapy has
      been the favoured approach, a combination of several therapeutic approaches is
      advocated. CONCLUSIONS: Problem and compulsive gambling can present a real health
      threat. As with other addictions, treatment strategies continue to be a baffling
      social problem. Aware and informed physicians can have a pivotal role in the
      difficult process of identifying, acknowledging, and remediating problem and
      compulsive gambling.

PMID- 10907573
TI  - Another 2-way MLV vaccine against agents of bovine respiratory disease.

PMID- 10907574
TI  - Further comments on veterinary chiropractic.

PMID- 10907575
TI  - An ethicist's commentary on the veterinarian who asks his employee to lie about a
      surgical death.

PMID- 10907576
TI  - The relationship between scrotal circumference at weaning and at one year of age
      in beef bulls.
AB  - Scrotal circumference data obtained from performance test station bulls were
      corrected to 240 and 365 days of age. Data were analyzed, retrospectively, to
      determine the outcome for scrotal circumference at 365 days of age, if bulls were
      culled at selected cut-off values for scrotal circumference at 240 days of age.
      The data indicate that scrotal circumference measurements in weaned bulls may not
      be useful as a culling tool, since a large proportion of bulls, irrespective of
      breed, fell below the selected cut-off measurement for scrotal circumference at
      weaning, but met the minimum scrotal circumference at one year of age. Scrotal
      circumference measurements at 240 days of age may, however, be useful as a tool
      for selecting bulls with a greater than 80% probability of achieving the minimum
      scrotal circumference measurement at one year of age.

PMID- 10907578
TI  - Pancreatitis associated with potassium bromide/phenobarbital combination therapy
      in epileptic dogs.
AB  - In a retrospective study, at least 10% of dogs receiving potassium
      bromide/phenobarbital combination therapy, compared with 0.3% of dogs receiving
      phenobarbital monotherapy, had probable pancreatitis. Pancreatitis may be a more
      frequent and more serious adverse effect of potassium bromide/phenobarbital
      combination therapy than has been reported previously.

PMID- 10907579
TI  - Halicephalobus gingivalis encephalomyelitis in a horse.
AB  - An 8-year-old, Arabian mare presented with acute progressive ataxia and a firm
      swelling over the right mandible. Radiographs revealed multiple radiolucent areas
      on the mandibles. The mare's neurological signs progressed, she was consequently
      euthanized. Postmortem examination revealed mandibular granulomatous reactions
      and meningoencephalitis due to the nematode Halicephalobus gingivalis.

PMID- 10907577
TI  - Characterization of acute interstitial pneumonia in cattle in southern Alberta
      feedyards.
AB  - Field data were collected over 2 consecutive years to characterize acute
      interstitial pneumonia (AIP) in feedyard cattle. Thirty-eight cattle with
      clinical symptoms of AIP were examined following emergency slaughter; 31 (all
      heifers) were confirmed to have AIP on the basis of gross and histological lung
      pathology. The 7 without AIP, plus 17 asymptomatic penmates, were used as
      contemporary controls. Plasma concentrations of 3-methylindole (3MI) metabolites
      were higher (P < 0.001) in heifers afflicted with AIP than in the control
      animals, and concentrations of 3MI mercapturates in the urine were lower (P <
      0.007) in affected heifers. Concentrations of 3MI adducts in lung tissue and in
      microsomal protein did not differ (P > 0.05) between the 2 groups, and 3MI was
      not detected in ruminal fluid from either group. Total ruminal bacterial numbers
      and populations of lactobacilli and protozoa were similar (P > 0.05) between the
      AIP-positive and unafflicted groups, but fewer (P < 0.05) cellulolytic bacteria
      were present in the positive group. Bovine respiratory syncytial virus antigen
      was not found in lung tissue from any of the heifers confirmed to have AIP. To
      our knowledge, this study is the first to implicate 3MI metabolites as having a
      role in feedyard AIP. Further research is required to determine the factors
      responsible for the elevation in 3MI adducts in plasma and urine of feedyard
      cattle afflicted with AIP.

PMID- 10907580
TI  - True hermaphroditism in a horned goat with 60XX/60XY chimerism.
AB  - Anatomical, behavioral, histological, endocrinological, and cytogenetic
      characteristics were determined in a horned intersex goat. Histology of the
      gonads confirmed that the goat was a true hermaphrodite. Cytogenetic analysis
      showed that it was a chimera (60XX/60XY). Use of laparoscopy allowed
      determination of characteristics of the internal gonads.

PMID- 10907581
TI  - Lead toxicosis in a puppy.
AB  - After showing clinical and radiographic signs of a gastrointestinal foreign body,
      a 5-month-old puppy began head pressing, which progressed to convulsions.
      Hematological abnormalities suggested lead poisoning; serum lead was 2.61
      mumol/L. The puppy made a complete recovery after intensive treatment for lead
      toxicosis.

PMID- 10907582
TI  - Multiple malformations in a newborn goat.

PMID- 10907583
TI  - Physical therapy.

PMID- 10907584
TI  - The pathobiology of acute asthma.
AB  - Acute bronchial asthma is a common problem with immense medical and economic
      impacts. It is estimated that this disease affects 12 to 14 million people in the
      United States with costs in excess of $6 billion per year. Most of the morbidity
      and all of the mortality of asthma tends to be associated with acute
      exacerbations, and treatment of these events accounts for the majority of
      expenditures in money and health care resources. Unfortunately, the factors that
      contribute to the destabilization of asthma are rarely studied and much of the
      pathogenesis and pathobiology of acute asthma remains unknown. This article
      examines these issues and suggests treatment for acute asthma.

PMID- 10907585
TI  - The pathology of chronic asthma.
AB  - Our understanding of the pathophysiology of asthma has undergone great advances
      in the past decade, particularly with the recognition of cytokines and the roles
      they may take in orchestrating the local immune response. With this information,
      it has been possible to target new therapeutic entities such as cytokine or
      chemokine receptors. Eosinophils and T lymphocytes have a special place in the
      inflammatory and structural alterations contributing to the asthmatic diathesis.
      It is possible that phenotype subsets of these cells exist and they hold the key
      to perpetuation of immunologic and physiologic abnormalities in asthma.

PMID- 10907586
TI  - Contributing factors to the pathobiology. The genetics of asthma.
AB  - Markers in 19 chromosomal regions have shown some evidence of linkage to asthma,
      atopy, or related phenotypes in multiple independent genome-wide searches.
      Linkages to five of these regions (5q, 6p, 11q, 12q, and 13q) have also been
      reported in non-genome-wide screens. In addition, at least two independent
      studies have reported linkages to markers on 16p. Numerous candidate genes in
      these regions have shown varying levels of association to asthma or atopic
      phenotypes, potentially implicating them as disease susceptibility loci. These
      include the IL4, CD14, and B2ADR genes on 5q, the HLA-DRB1 and TNF genes on 6p,
      the FCERB1 and CC16 genes on 11q, and the IL4RA gene on 16p. It still remains to
      be determined whether polymorphisms in these genes account for the reported
      linkages in these regions. Studies are underway in laboratories around the world
      to identify the disease-causing variations in these genes that account for the
      linkages just discussed. Identifying specific genetic polymorphisms that
      influence asthma and atopic phenotypes will shed light on the molecular pathways
      involved in these complex disorders and provide a better understanding of the
      pathophysiology of asthma and atopy.

PMID- 10907587
TI  - Contributing factors to the pathobiology of asthma. The Th1/Th2 paradigm.
AB  - CD4+ "helper" T-lymphocytes in murine and human models have been divided into Th1
      and Th2 subclasses, characterized by the profile of cytokines they secrete: INF
      gamma (and perhaps IL-2 and TNF-beta) by Th1 cells, and IL-4 (and perhaps IL-5,
      IL-6, IL-10, and IL-13) by Th2 cells. Although a strict division into Th1 and Th2
      phenotypes in humans (unlike murine systems) may not be possible, the asthmatic
      diathesis in humans appears to be one largely characterized by inflammatory
      responses associated with Th2 cells and their cytokines, particularly IL-4, IL
      13, and IL-5. Other pulmonary disorders, such as those associated with infectious
      diseases including tuberculosis, appear to favor an immunologic response
      characteristic of Th1-cells, and its defining cytokine IFN-gamma. This apparent
      Th1/Th2 immune dysregulation in asthma is an area of active investigation and
      forms the basis for ongoing attempts to change this phenotype through a variety
      of approaches. These include immunotherapy with conventional antigens, designer
      peptides, oligonucleotides, and anti-IgE, and pharmacotherapy with immune
      modulating drugs, cytokines, cytokine agonists and cytokine antagonists, and
      antibodies. This field of investigation promises to usher in a whole new approach
      to our understanding of asthma and ways to approach its treatment.

PMID- 10907588
TI  - The role of viruses in development or exacerbation of atopic asthma.
AB  - Respiratory viral infections in early childhood have been linked to the
      development of persistent wheezing and asthma. Epidemiologic data indicate that,
      for the majority of children, virus-induced wheezing is a self-limited condition,
      with no long-term consequences. For a substantial minority, however, virus
      induced wheezing is associated with persistent asthma and the potential for
      enhanced allergic sensitization. For the most part, this subset of patients is
      genetically predisposed; they are atopic children in whom respiratory viral
      infections trigger the early development of asthma by mechanisms that have not
      been fully elucidated. Both inflammatory and noninflammatory mechanisms may be
      involved. It does not appear that viral infection per se in early life is
      responsible for the induction of atopic asthma. Data from animal models provide
      support for the concept that enhanced allergic sensitization caused by increased
      uptake of allergen during infection may play a critical role, as well as T-cell
      mediated immune responses to viral infection, which may favor eosinophilic
      inflammatory responses and the development of altered airway function to inhaled
      methacholine. Recent advances in our understanding of the interactions between
      respiratory viruses and the development of reactive airway disease offer new
      possibilities for preventive treatment in children at risk for developing
      persistent wheezing and asthma exacerbation as a result of viral infection.

PMID- 10907589
TI  - The role of respiratory viruses in acute and chronic asthma.
AB  - Respiratory infections can have dual effects related to asthma. First, there is
      increasing evidence that severe infections with RSV and PIV in infancy can alter
      lung development and physiology to increase the risks of subsequent wheezing and
      asthma. Second, infections with common cold viruses and influenza commonly
      precipitate wheezing symptoms in children and adults who already have established
      asthma, and RV appears to be the most important virus in producing exacerbations
      of the disease. The principal mechanisms by which this occurs appears to be viral
      replication in epithelial cells, triggering a cascade of inflammation involving
      granulocytes, macrophages, T cells, and secreted cytokines and mediators. The
      inflammatory process, although essential to clear the infection, augments pre
      existing airway inflammation in asthma, leading to increased airway obstruction
      and lower respiratory tract symptoms. Greater understanding of virus-induced
      changes in inflammation and corresponding changes in airway physiology may lead
      to new therapeutic approaches to the treatment and prevention of virus-induced
      airway dysfunction.

PMID- 10907590
TI  - The role of bacterial infections in asthma.
AB  - In summary, bacterial organisms are clinically relevant contributors to asthma
      exacerbations, and have received much less attention than viruses in this
      process. Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella
      catarrhalis have been linked to asthma exacerbations, particularly when sinusitis
      is present. Treatment therefore should be directed toward these organisms if a
      bacterial cause is suspected. The atypical bacteria--specifically, C. pneumoniae
      and M. pneumoniae--deserve special attention. Data suggest a link between these
      organisms and the exacerbation of asthma, as well as suggest that these organisms
      may be causative in asthma development. The existing data are not conclusive, but
      are suggestive enough to drive studies evaluating them as a possible mechanism in
      asthma pathogenesis. An animal model evaluating M. pneumoniae and C. pneumoniae
      would be ideal, but at present no model exists in which chronic infection with
      these organisms results in bronchial hyperresponsiveness. There is active work in
      this area, however. Alternative investigations include continued evaluation of
      these organisms by several modalities, including culture, serology, and PCR,
      along with evaluation of the host response. Many questions remain, but the ground
      is fertile for continued investigation.

PMID- 10907591
TI  - Consequences of long-term inflammation. The natural history of asthma.
AB  - Although asthma is classically defined as reversible airflow obstruction, and
      often remits in younger subjects with milder disease, the natural history of
      asthma is that various degrees of airflow obstruction may persist and, in the
      long-term, asthma may become moderately to fully irreversible. Severe,
      irreversible airflow obstruction may develop despite apparently appropriate
      therapy and in the absence of other risk factors, such as smoking and
      environmental insults. All studies of subjects with persisting asthma show
      increased decline in lung function compared with normal subjects. Persistent
      abnormal physiology is reflected both in reduced airflow rates and in increased
      airway responsiveness. The cellular and molecular mechanisms of airway remodeling
      are described elsewhere in this issue. Questions not yet clearly answered are the
      reasons for these persistent abnormalities in some asthmatics, and which subjects
      are most at risk. Factors that adversely impact the outcome as adults identified
      relatively consistently among many longitudinal studies of the natural history of
      asthma include: Female gender. Environmental tobacco smoke exposure in childhood.
      Personal tobacco smoking in adolescence and adulthood. Age of onset of symptoms.
      Severity of childhood asthma. Duration of asthma. Severity of lung function
      abnormality in childhood. Bronchodilator reversibility. Degree of airway
      hyperresponsiveness. Delay in initiating anti-inflammatory therapy. Remission
      among adult asthmatics is uncommon, but is associated with better initial lung
      function, young age, male gender, and lesser degrees of airway responsiveness.
      The role of atopy remains controversial. Conversely, risk factors for death from
      asthma include older age, smoking, atopy, impaired lung function, and moderate to
      high reversibility. Treatment can improve lung function, reduce airway
      responsiveness, and improve quality of life. The overall effect of treatment on
      the natural history of the disease is not yet clear, despite significant short
      term improvements from effective anti-inflammatory therapy.

PMID- 10907592
TI  - Consequences of long-term inflammation. Airway remodeling.
AB  - Airway inflammation may not account for all the clinical manifestations of
      asthma. Airway remodeling, which is thought to be a result of airway chronic
      inflammation, may help fill this void. Remodeling is described for fatal and
      nonfatal asthmatics including changes in smooth muscle, collagen deposition,
      noncollagenous matrix, and mucus glands. This article also reviews the
      correlation of airway remodeling with clinical, physiologic and biologic data,
      experimental models of airways remodeling, and effect of therapy on airway
      remodeling. Throughout, it is emphasized that the concept of airway remodeling is
      a dynamic process that is active and potentially progressive in asthmatic
      patients but that may be prevented by appropriate therapy.

PMID- 10907593
TI  - Noninvasive measurement of airway inflammation using exhaled nitric oxide and
      induced sputum. Current status and future use.
AB  - The recent use of IS and the analysis of exhaled mediators such as NO are
      important steps forward in our ability to noninvasively assess airway
      inflammation without the need to resort to bronchoscopy. Exhaled NO and IS are
      complementary techniques that provide different information (Table 1). Induced
      sputum can provide knowledge regarding the cells and mediators participating in
      the inflammatory response, but is time consuming and expensive. Exhaled NO
      measurement is performed simply and quickly, and is a nonspecific marker of an
      inflammatory process. The initial capital costs of equipment for NO analysis are
      high, however. Once the problems of standardized collection and oropharyngeal
      contamination have been dealt with, BC may also prove to be an additional tool
      for the assessment of airway inflammation. It is likely that the next 10 years
      will see the establishment of these noninvasive tools for the clinical assessment
      of airway inflammation and oxidative stress, and change the entire way we manage
      asthma.

PMID- 10907594
TI  - Treatment of acute asthma. A new look at the old and at the new.
AB  - beta-Agonists remain the mainstay of therapy for acute asthma and, for most
      patients, standard doses are acceptable. Although the onset of action of systemic
      steroids is still not clear, steroids promote recovery and should be given to
      patients with acute illness. Intravenous magnesium sulfate appears to improve
      pulmonary function in the most severely ill patients but is not useful in
      patients with more moderate episodes. Ipratropium bromide is a weak
      bronchodilator that still needs to be tested as an adjunct to standard treatment
      regimens before its role in adults with asthma can be determined; given its ease
      of use and favorable safety profile it could be considered for patients with more
      severe acute illness. Aminophylline has not been found by most studies to improve
      outcomes and the narrow therapeutic range and unfavorable safety profile relegate
      it to a last-line agent or no use at all. Helium-oxygen mixtures currently have
      no role in moderately ill patients but have a theoretical advantage as a
      temporizing measure in severely ill patients. Drugs used in the management of
      chronic asthma, such as inhaled steroids and leukotriene-modifying agents, are
      making their way into the acute treatment arena, and other newly developed
      specific mediator inhibitors or blockers deserve attention. The use of isomers of
      beta-agonists is another area that is attracting attention and study. Systemic
      steroids are used to prevent relapse after emergency department discharge and the
      addition of other agents such as leukotriene-modifying agents or inhaled steroids
      may further prevent the need for urgent visits or hospitalization. The search for
      optimal treatment strategies for acutely ill patients is challenging and exciting
      and, with more attention and resources being devoted to this area, newer
      treatments will be found that will eventually have a greater impact on the high
      morbidity associated with acute asthma.

PMID- 10907595
TI  - The pathobiologic implications for treatment. Old and new strategies in the
      treatment of chronic asthma.
AB  - An increased understanding of the pathobiology of asthma has led to improved
      treatment for chronic asthma. This article discusses the old and new strategies
      of asthma therapy based on a pathobiologic approach. Therapeutic agents discussed
      include beta-adrenergic agonists, methylxanthines, corticosteroids, cromolyn,
      nedocromil, leukotriene modifiers, and new investigational agents.

PMID- 10907596
TI  - Early observations in radiculopathic pain control using electrodiagnostically
      derived new treatment techniques: automated twitch-obtaining intramuscular
      stimulation (ATOIMS) and electrical twitch-obtaining intramuscular stimulation
      (ETOIMS).
AB  - OBJECTIVE: To show in a pilot group of patients that electrodiagnostically
      derived new treatment techniques (automated twitch-obtaining intramuscular
      stimulation (ATOIMS) and electrical twitch-obtaining intramuscular stimulation
      (ETOIMS) methods) have a role in the control of radiculopathy related myofascial
      pain and fibromyalgia. METHOD: Retrospective analysis of six patients treated
      between 6-96 and 10-98. All received sequential treatments with ETOIMS and
      combined ATOIMS and ETOIMS of which four began treatments with standard TOIMS
      (StdTOIMS). The StdTOIMS utilized manual oscillation of a monopolar
      electromyographic (EMG) pin at tender muscle sites. ETOIMS employed
      microelectrical stimulation at 2 Hz for two seconds/site. The ATOIMS device
      automatically inserts and retracts a monopolar EMG pin after oscillating it at 2
      Hz for three cycles/two seconds/site. Obtaining forceful muscle twitches were the
      goals of all three treatments. Treatment included multiple points in bilateral
      multiple myotomes. Patients received weekly treatments and recorded daily visual
      analog pain levels. RESULTS: Significant reductions in pain levels occurred with
      the use of ETOIMS compared to that achieved with StdTOIMS. The combined use of
      ATOIMS and ETOIMS was more effective in reducing pain than StdTOIMS or ETOIMS
      only treatments. CONCLUSIONS: Control of radiculopathy related myofascial pain
      and fibromyalgia using the ETOIMS with ATOIMS methods seem promising. Reduction
      of mechanical tension through muscle relaxation is the proposed basis for the
      pain relief. There is a need for prospective studies to document efficacy in
      myofascial pain control.

PMID- 10907597
TI  - Current perception threshold: an adjunctive test for detection of acquired
      demyelinating polyneuropathies.
AB  - Current Perception Threshold (CPT) evaluation quantifies the sensory threshold to
      transcutaneous electrical stimulation of three sensory fiber subtypes: A-beta
      (2,000 Hz), A-delta (250 Hz) and C fibers (5 Hz). Demyelinating polyneuropathies
      tend to affect larger myelinated fibers before smaller unmyelinated fibers, and
      they usually begin at the proximal nerve roots or terminal axons, due to relative
      weakness of the blood-nerve barrier in these locations. Axonal polyneuropathies
      tend to affect smaller fibers before larger fibers, in a distal to proximal
      gradient. Ten patients with demyelinating polyneuropathy and ten patients with
      axonal polyneuropathy underwent CPT testing. CPT comparisons were made with
      regard to side-to-side asymmetries, fiber type involvement, and the ratio of
      fiber types involved. The C2, lateral antebrachial cutaneous, and sural
      distributions were examined bilaterally. Demyelinating polyneuropathies were
      detected with 50% sensitivity and 100% specificity. This diagnostic sensitivity
      is similar to that of published criteria based upon motor nerve conduction. CPT
      testing can distinguish demyelinating from axonal polyneuropathies. It may be
      particularly helpful in patients with predominantly sensory symptoms in whom
      EMG/NCS data may be equivocal, or in patients who decline EMG/NCS studies.

PMID- 10907598
TI  - Assessment of serum-mediated neurotoxicity in Navajo neuropathy.
AB  - Navajo neuropathy is a unique sensorimotor neuropathy which is geographically
      restricted to Navajo children living on the Navajo Reservation. Affected patients
      present with weakness, loss of sensation in extremities, corneal ulcerations, and
      a high incidence of childhood infections. Metabolic complications, such as severe
      liver disease, may further contribute to peripheral nerve injury in affected
      patients. In this study, serum-mediated injury to rat peripheral nerve was
      critically assessed. Serum samples from affected Navajo patients were tested in
      vivo for effects on peripheral nerve function. Injection of serum from affected
      Navajo patients into rat sciatic nerve produced a modest slowing of nerve
      conduction velocity without effecting evoked-compound muscle action potential
      (CMAP) amplitudes. By comparison, injection of serum from patients with MGUS
      neuropathy, an immune-mediated disorder, diminished evoked-CMAP amplitudes by
      approximately 70%. Navajo neuropathy sera had no effect in vitro on the neurite
      outgrowth of developing dorsal root ganglia neurons. The results argue against
      serum-mediated toxic injury to peripheral nerves in Navajo neuropathy.

PMID- 10907599
TI  - Mapping of the human upper arm muscle activity with an electrode matrix.
AB  - Surface electrode matrices allow measurement of muscle activity while avoiding
      certain hazardous risks and inconvenience associated with invasive techniques.
      Major challenges of such equipment involve optimizing spatial resolution, and
      designing simple acquisition systems able to record simultaneously many
      potentials over large anatomical areas. We present a surface electromyography
      acquisition system comprising of 3 x 8 Ag-AgCl electrodes mounted onto an elastic
      band, which can be adjusted to fit an entire human upper limb segment. Using this
      equipment, we acquired a simultaneous representation of muscular activity from a
      segment of the upper limb surface of 6 healthy subjects during isometric
      contractions at various intensities. We found that the location of regions of
      highest activity depended on elbow torque direction but also varied among
      subjects. Signals obtained with such equipment can be used to solve the inverse
      problem and help optimize the electrode configuration in volume conduction
      studies. The efficacy of decision algorithms of multi-functional myoelectric
      prostheses can be tested with the global muscle activity patterns gathered. The
      electrode cuff could also be used in the investigation of fatigue and injury
      mechanisms during occupational activities.

PMID- 10907600
TI  - On the inter- and intra-subject variability of the electromyographic signal in
      isometric contractions.
AB  - The objective of the present study was to evaluate the variability of the surface
      EMG signal of the same muscle in healthy subjects, because of lack of
      reproducibility of the EMG signal for the same subject and muscle in different
      trials of maximal isometric voluntary contraction. The results showed an EMG
      coefficient of variability of 21.61%, indicating that this variability must be
      considered in experiments with an inappropriate condition for normalization
      procedures, such as EMG biofeedback in rehabilitation sessions, or normalization
      procedures by the maximal isometric voluntary contraction.

PMID- 10907601
TI  - Electrodiagnostic examination of lumbosacral radiculopathies.
AB  - To determine the diagnostic efficacy of late responses and of magnetic
      stimulation in the electrodiagnostic evaluation of lumbosacral radiculopathies,
      42 patients with acute monoradiculopathies of L5 or S1 were examined. We
      performed conventional nerve conduction studies, F-wave studies, needle electrode
      examination (NEE) and magnetic stimulation. The results were compared with a
      control group of 36 persons. In the patients with weakness, we found a diagnostic
      sensitivity for NEE of 90% in L5 and of 80% in S1. F-waves had the same
      sensitivity as NEE in the patients with weakness and were more sensitive in the
      group of patients without weakness (L5 80%, S1 67%). Magnetic stimulation had a
      sensitivity of 40% in all groups. There were also abnormalities of NEE and of F
      wave studies in the patients with abnormal magnetic stimulation. It is concluded
      that NEE is the single most effective method in acute LSR and that F-wave studies
      are able to provide complementary information. Magnetically evoked motor nerve
      root stimulation was not found of clinically relevant diagnostic value.

PMID- 10907602
TI  - Two consecutive fasciculation potentials having different motor unit origins are
      an electromyographically pathognomonic finding of ALS.
AB  - To electrophysiologically diagnose amyotrophic lateral sclerosis (ALS),
      fasciculation potentials (FPs) were evaluated in each wasted muscle in 12 ALS and
      14 other neurogenic disorders (non-ALS patients). Various types of FPs were
      observed in ALS. The number of discharged FPs and firing rate of FPs were
      significantly increased in ALS compared to those in non-ALS. These findings
      indicate that more motor units take part in discharging FPs in ALS than in non
      ALS, and that injured lower motor neurons exhibit hyperexcitability. Although
      nine of 12 ALS patients showed two consecutive FPs having different motor unit
      origins, non-ALS patients did not show such FPs. Since the two consecutive FPs
      having different motor unit origins reflect an involvement of both upper and
      lower motor neurons, these potentials are an electrophysiologically pathognomonic
      finding to ALS.

PMID- 10907603
TI  - Progression of visual evoked potential abnormalities in multiple sclerosis and
      optic neuritis.
AB  - To investigate visual signal processing in patients with optic neuritis,
      suspected multiple sclerosis, confirmed multiple sclerosis (MS), and optic
      neuritis combined with MS, pattern reversal visual evoked potentials (VEPs) were
      recorded in patients and normal subjects. The amplitude and latency of the first
      positive peak, P100 were determined to assess electrical conduction in patients
      as compared to normal subjects. Suspected MS patients did not differ from normal
      subjects in peak latencies or amplitudes. The P100 amplitude was reduced in optic
      neuritis, confirmed MS and optic neuritis combined with confirmed MS. The P100
      and N145 latencies were prolonged in optic neuritis patients and confirmed MS
      patients as compared to normal subjects. The main characteristic of optic
      neuritis was P100 amplitude reduction, and of confirmed MS was P100 latency
      delay. There was a progression of the P100 latency delay and of the P100
      amplitude decrement in optic neuritis, confirmed MS, and optic neuritis combined
      with confirmed MS. These results indicate a progression of demyelination in optic
      neuritis, confirmed MS, and optic neuritis combined with confirmed MS.

PMID- 10907604
TI  - Ulnar-to-median nerve anastomosis in the forearm. Review and report of 2 new
      cases.
AB  - The ulnar-to-median nerve anastomosis in the forearm is a very rare occurrence,
      not mentioned in many anatomical text books. We found only 4 cases cited in
      medical literature. Here we describe 2 new cases, for which diagnosis was
      suspected when the compound muscle action potential of the abductor pollicis
      brevis muscle (APB), obtained by maximal stimulation of the median nerve at the
      elbow, was lower than that obtained at the wrist. The diagnosis was confirmed by
      stimulation of the ulnar nerve at the elbow, which evoked a compound muscle
      action potential of the APB with a clear negative initial deflection without
      volume-conducted potential.

PMID- 10907605
TI  - [New developments in the diagnosis and treatment of schizophrenia. 7th Hand Jorg
      Weitbrecht Symposium, Leverkusen].

PMID- 10907606
TI  - [Schizophrenia and the quality of life].
AB  - This paper discusses opportunities and constraints for psychiatry to exert an
      influence on the quality of life of people suffering from schizophrenia. Using
      the example of neuroleptic drug treatment, the opportunities to both positively
      and adversely affect quality of life by means of psychiatric treatment are
      illustrated. De-institutionalisation was used as an example for demonstrating the
      effect of the quality of mental health services. The fact that efforts on the
      part of professional helpers to achieve improvements in their patients' quality
      of life are constrained by existing economic and socio-cultural conditions is
      shown by discussing the stigmatization of people with schizophrenia and their
      situation on the labour market.

PMID- 10907607
TI  - [Health economics and evaluation of schizophrenic psychoses in Germany].
AB  - This paper presents a survey of economic analyses of schizophrenia in Germany. A
      recently published cost-of-illness study demonstrates the high financial burden
      to society caused by the disease. Ambulatory care and medication were remarkably
      less costly than in-patient treatment. Several other studies show that continuous
      in-patient treatment is less cost-effective than complementary care in the
      community. Two pharmaco-economic models evaluate drugs with special focus on long
      term treatment. Drugs with better compliance rates seem to produce savings in the
      health care system by less hospital admissions, even if the drug is more
      expensive than other medication. In addition to the survey the problems of
      economic analysis of psychiatric disorders in Germany are discussed. There are
      difficulties caused by the structure of the German health care system. Other
      problems emerge from the measurement of outcomes, effectiveness, utilities and
      quality of life in psychiatric disorders.

PMID- 10907608
TI  - [Is the diagnosis of schizophrenic illness possible in the initial prodromal
      phase to the first psychotic manifestation?].
AB  - In the international research on schizophrenia, the early detection and
      intervention already in the initial prodromal phase prior to the first psychotic
      manifestation has become one of the main aims in recent years. Therefore, in the
      present study, the diagnostic efficiency of initial prodromal symptoms was
      examined prospectively for the first time ever. At index-examination, patients
      were examined with the 'Bonn Scale for the Assessment of Basic Symptoms--BSABS'
      and the ninth version of the 'Present State Examination--PSE 9'. At that time,
      none of the 160 patients had shown psychotic symptoms, but in 110 of the cases
      prodromal symptoms were found. At the reexamination that took place in average
      9.6 years later, patients were explored with regard to a meantime transition to a
      first psychotic episode applying the same instruments as at index-examination. 79
      of the 160 patients (49.38%) had developed a schizophrenic disorder according to
      DSM-IV-criteria in the catamnestic interval. In general, the 66 assessed
      prodromal symptoms exhibited a high sensitivity (.98), a high negative predictive
      power (.96) and a low percentage of false-negative predictions (1.3%), but lower
      values of specificity (.59) and positive predictive power (.70) as well as a
      higher percentage of false-positive predictions (20.6%). However, for a subset of
      mainly cognitive prodromal symptoms with a sensitivity sufficient for diagnostic
      criteria, high specificities (.85-.91) and positive predictive powers (.71-.91)
      as well as satisfactory percentages of false-positive predictions (7.5%-1.9%),
      and good classification rates (81.25%) were found. The results show that the
      applied conceptualization of prodromal symptoms that originates in the German
      psychopathological tradition is indeed useful for an early detection of
      psychoses. By assessing those prodromal symptoms, which were proven to be highly
      predictive, a diagnosis of schizophrenic disorders already seems possible in the
      initial prodrome. Thus in future, an early intervention related to them might
      enable a prevention of first psychotic episodes.

PMID- 10907609
TI  - [Acute and transient psychotic disorders].
AB  - Psychotic disorders with acute onset, a dramatic and polymorphous symptomatology
      and rapid resolution have been described in different countries and by different
      psychiatric schools. They have been called cycloid psychosis, bouffee delirante,
      psychogenic psychosis or good prognosis schizophrenia. ICD-10 has given an
      operational definition under the name "acute and transient psychotic disorders"
      (F23). Their nosological status is unclear. The Halle-Study of acute and
      transient psychotic disorders (ATPD) has investigated in a prospective manner
      clinical, para-clinical features and course of illness in 42 patients with ATPD
      and matched controls with positive schizophrenia, bipolar schizoaffective
      disorders as well as mentally healthy patients with acute surgical conditions.
      First results of our study show that ATPD amount to 4% of psychotic in-patients,
      prefer female sex, show short prodromi, marked affective disturbances within the
      episode and much better outcome as schizophrenic psychoses according to
      psychopathological, social, psychological and biographical criteria. Though ATPD
      may still be an inhomogeneous group, their clinical delineation from
      schizophrenia seems justified.

PMID- 10907610
TI  - [Long-term medication in schizophrenic psychoses].
AB  - Schizophrenia is a relapsing disorder. The main goal of neuroleptic maintenance
      treatment is relapse prevention, which is empirically well proven. Availability
      of different kinds of treatment strategies including new antipsychotic drugs with
      improved risk/benefit profile allow long-term treatment to be individually
      tailored. Treatment guidelines developed mainly by the scientific medical
      societies can help the practitioner in making the right decisions.

PMID- 10907611
TI  - [The chances of new atypical substances].
AB  - Antipsychotic treatment with so-called "atypical" neuroleptics, as defined by the
      lack of extrapyramidal side effects in its strict sense, has made great advances
      in the last decades with the advent of newly developed antipsychotic agents. The
      first atypical neuroleptic drug was clozapine, also referred to as "dirty drug"
      or "rich drug" because of its broad receptor binding profile. Clozapine has been
      the starting point for several different, newly developed antipsychotics. Among
      these, the most prominent are olanzapine, risperidone, sertindol, ziprasidone,
      and amisulpride. All of these newly developed, atypical antipsychotics show a
      high degree of efficacy in the treatment of positive symptoms of schizophrenia in
      combination with a lack of or a reduced degree of extrapyramidal side effects
      (EPS). In addition, several atypical antipsychotics seem to have an additional
      impact on negative symptoms such as alogia, anhedonia, or avolition. However,
      apart from the clear advantage of clozapine in the treatment of otherwise
      treatment-resistant schizophrenia, differential indications for the different
      antipsychotics remain to be established.

PMID- 10907612
TI  - [Flupenthixol--a partial atypical neuroleptic?].
AB  - There is no really clear-cut definition for "atypical" neuroleptics. The most
      convincing definition is draft by characterization of the receptor-binding
      profile. Most important are: the combined antagonism of D2 and 5-HT2 receptors,
      the preferential binding to D4 and D3 receptors and a balanced relation of D2 to
      D1 antagonism. Flupentixol fits into this description as well as some modern
      neuroleptics widely considered as "atypical" neuroleptics. Clinical criteria-
      like the absence of EPMS and the improvement of negative symptoms--offer no clear
      cut distinction between "typical" and "atypical" neuroleptics, too, because some
      modern "atypical" neuroleptics lead--dose-dependent--to EPMS, and there is no
      proven efficacy for some atypical neuroleptics in the treatment of negative
      symptoms. So, neuroleptics are labelled "atypical" if there is a favourable
      relation between antipsychotic activity and the degree of EPMS, and if there is
      at least some efficacy in the treatment of negative symptoms. In this regard,
      Flupentixol has to be labelled at least a "partial atypical neuroleptic".

PMID- 10907613
TI  - [D2-dopamine receptor upregulation and treatment response under neuroleptic
      therapy].
AB  - Animal and post mortem studies indicate that neuroleptic therapy may induce D2
      dopamine receptor upregulation in the basal ganglia. To address this phenomenon
      in a clinical study, we investigated the D2-dopamine receptor binding in 15 DSM
      III-R schizophrenics in the drug-naive state and three days after completion of a
      standardized neuroleptic therapy (benperidol 12-16 mg/d for 25 days) using single
      photon emission computed tomography (SPECT). SPECT scans were obtained 2 h after
      intravenous injection of 185 MBq 123I-IBZM. For analysis, basal ganglia to
      frontal cortex (BG/FC) ratios were calculated and the patient sample was
      subgrouped into patients with a favourable versus a poor treatment response.
      Neuroleptic treatment led to decreased BG/FC ratios in patients with a favourable
      response, but increased ratios in the poor responders (df = 1, F = 4.1, p =
      0.06). Changes of BG/FC ratios were significantly correlated with extrapyramidal
      side effects, but not with neurological soft signs (NSS). Our findings indicate
      that neuroleptic therapy induces D2-dopamine receptor upregulation in a subgroup
      of patients characterized by poor treatment response and pronounced
      extrapyramidal side effects.

PMID- 10907614
TI  - [Family therapy for schizophrenia].
AB  - Family therapy has long been conceived and practised under etiological premises.
      Familial disturbances as pathological regression/fixation (psychoanalytical) and
      individuation-impairing family dynamics (systemic) were addressed directly in the
      hope of "curing" the disorder. The efforts to prove the viability of the concepts
      and/or the efficacy of the therapeutic approach were largely unsuccessful. Newer
      strategies of family therapy of schizophrenia are both more precise in their
      theoretical assumptions and more performing in the pursuit of their therapeutic
      goals. We analyse the basis of modern family therapy in the "Expressed-Emotions"
      research and propose a newer, more adequate understanding of the EE phenomenon.
      From our own studies and from a general review of relevant studies we derive an
      understanding of the rationale of family work and family therapy of
      schizophrenia. We discuss the results of a meta-analysis on the active
      ingredients and the conditions of efficacy of family interventions.

PMID- 10907615
TI  - [Cognitive therapy for schizophrenic patients].
AB  - Neurocognitive deficits of schizophrenic patients are assigned to the following
      three levels of disorders: Information-processing, basic styles of thinking and
      emotional management. Cognitive interventions are schematically subdivided in
      direct, indirect and combined ones. Direct interventions are oriented straight at
      the disorder and contain exactly definable therapeutic steps inside of an
      experimental procedure. The focus of indirect interventions are the environment
      of the disorder with the purpose of modification and reorganisation. Combined
      interventions connect both approaches to get a decrease of the impairments of the
      symptoms and a long-term stabilization. Today, connections between the pattern of
      cognitive dysfunctions and the social functioning of schizophrenic patients are
      investigated. Verbal memory and vigilance seem to be good predictors of the
      community functioning. Further developments of cognitive therapies have to
      include multimodal approaches and unspecific therapeutic influences.

PMID- 10907616
TI  - TCAs or SSRIs as initial therapy for depression?

PMID- 10907617
TI  - Integrated screening for Down's syndrome.

PMID- 10907619
TI  - Soy formulations in the treatment of diarrhea.

PMID- 10907618
TI  - Do fish oils or vitamin E reduce morbidity and mortality after myocardial
      infarction?

PMID- 10907620
TI  - The good old days still lie ahead.

PMID- 10907622
TI  - HIV-risk practices among homeless and low-income housed mothers.
AB  - BACKGROUND: Knowledge of human immunodeficiency virus (HIV) and its risk
      behaviors have not been systematically studied in homeless mothers. The
      identification of the factors associated with HIV-risk practices will guide
      interventions for low-income housed and homeless women. METHODS: We interviewed
      220 homeless and 216 low-income housed mothers living in Worcester,
      Massachusetts, to gather information on demographic, psychosocial , and HIV-risk
      practice characteristics. We used standardized instruments and questions drawn
      from national surveys. The primary study outcome was high HIV-risk behavior.
      RESULTS: Although homeless mothers were more likely than low-income housed
      mothers to report first sexual contact at an early age, multiple partners during
      the last 6 months, and a history of intravenous drug use, homelessness was not
      associated with high HIV-risk practices. Both homeless and low-income housed
      mothers demonstrated misconceptions about HIV transmission through casual
      contact. Among high-risk women, approximately 75% perceived themselves as having
      low or no risk for contracting HIV. A history of childhood victimization, adult
      partner violence, or both placed women at a significantly increased likelihood of
      high HIV-risk practices. African American race, knowledge about HIV, and self
      perception of risk were also significantly associated with high-risk practices.
      CONCLUSIONS: Homeless mothers are a subgroup of poor women at high risk for HIV
      and should be targeted for preventive interventions. In addition, there are
      potentially modifiable factors associated with HIV-risk practices in both low
      income housed and homeless mothers that should be directly addressed.

PMID- 10907623
TI  - Magnesium for the treatment of nocturnal leg cramps: a crossover randomized
      trial.
AB  - BACKGROUND: Nocturnal leg cramps are a common health problem in the ambulatory
      setting. Our objective was to evaluate the efficacy of magnesium in the treatment
      of nocturnal leg cramps. METHODS: Our study was a crossover randomized double
      blind placebo-controlled trial. We included patients from a large university
      based ambulatory clinic in Buenos Aires, Argentina, with at least 6 cramps during
      the previous month. A total of 93 subjects took part in a 4-week washout period
      with placebo. Those who were still eligible (n = 45) were randomized to receive
      either (1) an oral dose of 900 mg magnesium citrate twice daily for 1 month,
      followed by a matching placebo for 1 month, or (2) the placebo first, followed by
      magnesium. Both groups had a 4-week washout period with placebo between each
      treatment month. Forty-two patients completed the 4-month study. The main outcome
      was the number of nocturnal leg cramps, and the secondary outcomes were duration,
      severity, and sleep disorders caused by those cramps. RESULTS: There were no
      significant differences between magnesium and placebo in any of the evaluated
      outcomes. The mean number of cramps was 11.1 (standard deviation [SD] +/- 7.3)
      for placebo versus 11.8 (SD +/- 7.6) for magnesium (P = .59). We observed a
      significant period-effect bias: All patients improved over time regardless of the
      treatment sequence they received. CONCLUSIONS: Magnesium was not effective for
      the treatment of nocturnal leg cramps. The period-effect bias probably occurred
      because of a combination of the natural history of this condition, a regression
      to the mean, and a true placebo effect.

PMID- 10907621
TI  - The effects of physician supply on the early detection of colorectal cancer.
AB  - BACKGROUND: Policymakers question whether there is a relationship between the
      number and distribution of physicians and the outcomes for important health
      conditions. We hypothesized that increasing primary care physician supply would
      be related to earlier detection of colorectal cancer. METHODS: We identified
      incident cases of colorectal cancer occurring in Florida in 1994 (n = 8,933) from
      the state cancer registry. We then obtained measures of physician supply from the
      1994 American Medical Association Physician Masterfile and examined the effects
      of physician supply (at the levels of county and ZIP code clusters) on the odds
      of late-stage diagnosis using multiple logistic regression. RESULTS: For each 10
      percentile increase in primary care physician supply at the county level, the
      odds of late-stage diagnosis decreased by 5% (adjusted odds ratio [OR] = 0.95;
      95% confidence interval [CI], 0.92 - 0.99; P = .007). For each 10-percentile
      increase in specialty physician supply, the odds of late-stage diagnosis
      increased by 5% (adjusted OR = 1.05; 95% CI, 1.02-1.09; P = .006). Within ZIP
      code clusters, each 10-percentile increase in the supply of general internists
      was associated with a 3% decrease in the odds of late-stage diagnosis (OR = 0.97;
      95% CI, 0.95 - 0.99; P = .006), and among women, each 10-percentile increase in
      the supply of obstetrician/gynecologists was associated with a 5% increase in the
      odds of late-stage diagnosis (OR = 1.05; 95% CI, 1.01 - 1.08; P = .005).
      CONCLUSIONS: If the relationships observed were causal, then as many as 874 of
      the 5463 (16%) late-stage colorectal cancer diagnoses are attributable to the
      physician specialty supply found in Florida. These findings suggest that an
      appropriate balance of primary care and specialty physicians may be important in
      achieving optimal health outcomes.

PMID- 10907624
TI  - A taxonomy of requests by patients (TORP): a new system for understanding
      clinical negotiation in office practice.
AB  - BACKGROUND: The goal of our investigation was to facilitate research on clinical
      negotiation between patients and physicians by developing a reliable and valid
      classification system for patients' requests in office practice. METHODS: We
      developed the Taxonomy of Requests by Patients (TORP) using input from
      researchers, clinicians, and patient focus groups. To assess the system's
      reliability and validity, we applied TORP to audiotaped encounters between 139
      patients and 6 northern California internists. Reliability was assessed with the
      kappa statistic as a measure of interrater agreement. Face validity was assessed
      through expert and patient judgment of the coding system. Content validity was
      examined by monitoring the incidence of unclassifiable requests. Construct
      validity was evaluated by examining the relationship between patient requests and
      patient health status; patient request fulfillment and patient satisfaction; and
      patient requests and physician perceptions of the visit. RESULTS: The 139
      patients made 772 requests (619 requests for information and 153 requests for
      physician action). Average interrater agreement across a sample of 40 cases was
      94% (kappa = 0.93; P <.001). Patients with better health status made fewer
      requests (r = -0.17; P = .048). Having more chronic diseases was associated with
      more requests for physician action (r = 0.32; P = .0002). Patients with more
      unfulfilled requests had lower visit satisfaction (r = -0.32; P <.001). More
      patient requests was also associated with physician reports of longer visit times
      (P = .016) and increased visit demands (P = .006). CONCLUSIONS: Our study
      provides evidence that TORP is a reliable and valid system for capturing and
      categorizing patients' requests in adult primary care. Further research is needed
      to confirm the system's validity, expand its applicability, and explore its
      usefulness as a tool for studying clinical negotiation.

PMID- 10907625
TI  - Troglitazone or metformin in combination with sulfonylureas for patients with
      type 2 diabetes?
AB  - BACKGROUND: Combination oral therapy is often used to control the hyperglycemia
      of patients with type 2 diabetes. We compared the effectiveness of metformin and
      troglitazone when added to sulfonylurea therapy for patients with type 2 diabetes
      who had suboptimal blood glucose control. METHODS: We used a randomized 2-group
      design to compare the efficacy, safety, and tolerability of troglitazone and
      metformin for patients with type 2 diabetes mellitus that was inadequately
      controlled with diet and oral sulfonylureas. Thirty-two subjects were randomized
      to receive either troglitazone or metformin for 14 weeks, including a 2-week drug
      titration period. The primary outcome variable was mean change in the level of
      glycosylated hemoglobin (Hb A1c) from baseline. Secondary outcomes included mean
      changes from baseline in fasting plasma glucose and C-peptide levels, renal or
      metabolic side effects, and symptomatic tolerability. RESULTS: The addition of
      either troglitazone or metformin to oral sulfonylurea therapy significantly
      decreased Hb A1c levels. Both treatment regimens also significantly reduced
      fasting plasma glucose and C-peptide levels. We found no significant differences
      between the treatment arms in efficacy, metabolic side effects, or tolerability.
      CONCLUSIONS: Our results demonstrate that troglitazone and metformin each
      significantly improved Hb A1c, fasting plasma glucose, and C-peptide levels when
      added to oral sulfonylurea therapy for patients with type 2 diabetes who had
      inadequate glucose control.

PMID- 10907626
TI  - Bacterial vaginosis in pregnancy and the risk of prematurity: a meta-analysis.
AB  - OBJECTIVE: We conducted this meta-analysis to determine the magnitude of risk
      conferred by bacterial vaginosis during pregnancy on preterm delivery. SEARCH
      STRATEGY: We selected articles from a combination of the results of a MEDLINE
      search (1966-1996), a manual search of bibliographies, and contact with leading
      researchers. SELECTION CRITERIA: We included case control and cohort studies
      evaluating the risk of preterm delivery, low birth weight, preterm premature
      rupture of membranes, or preterm labor for pregnant women who had bacterial
      vaginosis and those who did not. DATA COLLECTION AND ANALYSIS. Two investigators
      independently conducted literature searches, applied inclusion criteria,
      performed data extraction, and critically appraised included studies. Summary
      estimates of risk were calculated as odds ratios (ORs) using the fixed and random
      effects models. MAIN RESULTS: We included 19 studies in the final analysis.
      Bacterial vaginosis during pregnancy was associated with a statistically
      significant increased risk for all outcomes evaluated. In the subanalyses for
      preterm delivery, bacterial vaginosis remained a significant risk factor. Pooling
      adjusted ORs yielded a 60% increased risk of preterm delivery given the presence
      of bacterial vaginosis. CONCLUSIONS: Bacterial vaginosis is an important risk
      factor for prematurity and pregnancy morbidity. Further studies will help clarify
      the benefits of treating bacterial vaginosis and the potential role of screening
      during pregnancy.

PMID- 10907627
TI  - To screen or not to screen? Bacterial vaginosis in pregnancy.

PMID- 10907628
TI  - Primary care physicians' views on screening and management of alcohol abuse:
      inconsistencies with national guidelines.
AB  - BACKGROUND: The effects of patients' abuse of and dependence on alcohol are well
      known, but screening for problem drinking by primary care physicians has been
      limited. The National Institute of Alcohol Abuse and Alcoholism (NIAAA)
      recommends that all patients be screened for alcohol use, all users be screened
      with the CAGE questionnaire, and all nondependent problem drinkers be counseled.
      We evaluated primary care physicians' screening methods for alcohol use and their
      management of problem drinkers to determine if they were following the NIAAA
      guidelines. METHODS: We mailed a questionnaire to 210 internists and family
      physicians to assess their alcohol screening and management methods. RESULTS:
      Only 64.9% of the respondents reported screening 80% to 100% of their patients
      for alcohol abuse or dependence during the initial visit; even less (34.4%)
      screened that many patients during an annual visit. Nearly all respondents (95%)
      reported "frequently" or "always" using quantity-frequency questions to screen
      for alcohol abuse, but only 35% "frequently" or "always" used the CAGE
      questionnaire. Only 20% of the respondents rated treatment resources as adequate
      for early problem drinkers, and 72% preferred not to counsel these patients
      themselves. A belief that a primary care physician could have a positive impact
      on an alcohol abuser was less likely to be held by respondents who were older, in
      a nonurban setting, or had more years in practice (P = .05). CONCLUSIONS: A
      substantial proportion of the physicians in our survey sample were not following
      NIAAA recommendations. Most physicians preferred not to do the counseling of
      nondependent problem drinkers themselves, but to refer those patients to a nurse
      trained in behavioral interventions.

PMID- 10907629
TI  - The development and goals of the AAFP center for policy studies in family
      practice and primary care. American Academy of Family Physicians.
AB  - In this article we describe the creation and role of the Center for Policy
      Studies in Family Practice and Primary Care established by the American Academy
      of Family Physicians in Washington, DC, this year. We recount the events leading
      to the decision to implement the Center, list its guiding assumptions, and
      explain its initial structure and function. We also identify the 3 themes that
      will guide the early work of the Center: sustaining the functional domain of
      family practice and primary care; investing in key infrastructures; and securing
      universal health coverage.

PMID- 10907632
TI  - Accuracy of hematuria in diagnosing kidney stones.

PMID- 10907631
TI  - Oral or IV antibiotics for the treatment of febrile children with UTIs?

PMID- 10907630
TI  - Reduction of vertebral fracture risk with raloxifene.

PMID- 10907633
TI  - Cost-effectiveness analysis of management of sore throats in children.

PMID- 10907635
TI  - Standardization of hematopoietic stem cell assays: a summary of a workshop and
      working group meeting sponsored by the National Heart, Lung, and Blood Institute
      held at the National Institutes of Health, Bethesda, MD on September 8-9, 1998
      and July 30, 1999.

PMID- 10907634
TI  - Is the COX-2 effect on accelerated hematopoiesis mediated by prostaglandin E2?

PMID- 10907636
TI  - Lack of efficacy of thrombopoietin and granulocyte-macrophage colony-stimulating
      factor after total body irradiation and autologous bone marrow transplantation in
      Rhesus monkeys.
AB  - OBJECTIVE: If administered in a sufficiently high dose to overcome receptor
      mediated clearance and in a well-scheduled manner, thrombopoietin (TPO)
      prominently stimulates hematopoietic reconstitution following myelosuppressive
      treatment and potentiates the efficacy of both granulocyte-macrophage colony
      stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF).
      However, TPO alone is not effective after bone marrow transplantation. Based on
      results of GM-CSF and TPO treatment after myelosuppression that resulted in
      augmented thrombocyte, reticulocyte, and leukocyte regeneration, we evaluated
      TPO/GM-CSF treatment after lethal irradiation followed by autologous bone marrow
      transplantation. MATERIALS AND METHODS: Young adult Rhesus monkeys were subjected
      to 8-Gy total body irradiation (TBI) (x-rays) followed by transplantation of
      10(7)/kg unfractionated bone marrow cells. TPO 5 microg/kg was administered
      intravenously at day 0 to obtain rapidly high levels. Animals then were treated
      with 5 microg/kg Rhesus TPO and 25 microg/kg GM-CSF given SC on days 1 to 14
      after TBI. RESULTS: The grafts shortened the profound pancytopenia induced by 8
      Gy TBI from 5-6 weeks to 3 weeks. The combination of TPO and GM-CSF did not
      significantly influence the recovery patterns of thrombocytes (p = 0.39),
      reticulocytes (p = 0.08), white blood cells (p = 0.08), or bone marrow
      progenitors compared to TPO alone. CONCLUSIONS: The present study demonstrates
      that, after high-dose TBI and transplantation of a limited number of
      unfractionated bone marrow cells, simultaneous administration of TPO and GM-CSF
      after TBI is ineffective in preventing pancytopenia. This result contrasts
      sharply with the prominent stimulation observed in a 5-Gy TBI myelosuppression
      model, despite a similar level of pancytopenia in the 8-Gy model of the present
      study. The discordant results of this growth factor combination in these two
      models may imply codependence of the hematopoietic response to TPO and/or GM-CSF
      on other factors or cytokines.

PMID- 10907637
TI  - Modulation of transduced erythropoietin expression by iron.
AB  - OBJECTIVE: Future prospects for gene therapy of chronic anemias involve
      expression of the erythropoietin transgene, which is regulated by oxygen tension.
      However, other factors such as cytokines or the iron load of erythropoietin
      expressing cells can concomitantly modulate transgene expression, as shown for
      the expression of the endogenous erythropoietin gene in human cell lines and in
      animals. We tested the effects of iron overload or depletion on the expression of
      the mouse erythropoietin transgene (cDNA), driven by the hypoxia-regulated
      phosphoglycerate kinase 1 promoter. MATERIALS AND METHODS: Retrovirally
      transduced mouse cells (C3H fibroblasts or C2C12 myoblasts) were cultured in
      normoxia (room air, O2: 21%) or hypoxia (O2: 1.5%) in the presence or absence of
      hemin (an iron donor) or deferiprone (an iron chelator), both of which easily
      enter the cell. RESULTS: Hemin inhibited the hypoxia-induced expression of the
      transgene. In contrast, deferiprone enhanced the hypoxia-induced expression of
      the erythropoietin transgene and induced its expression in normoxia. CONCLUSION:
      These results show that, in addition to oxygen partial pressure, the
      intracellular iron content is critical in the modulation of hypoxia-regulated
      erythropoietin transgene expression.

PMID- 10907638
TI  - Gene transfer to ankyrin-deficient bone marrow corrects spherocytosis in vitro.
AB  - OBJECTIVE: The goal of this study was to transfer by retroviral vector the cDNA
      for ankyrin to progenitors from normal bone marrow and from the nb/nb
      spherocytosis mutant deficient in expression of full-length ankyrin to achieve
      erythroid expression of functional ankyrin protein. MATERIALS AND METHODS: A
      minigene composed of the human ankyrin promoter, murine ankyrin cDNA, and the 3'
      human domain corresponding to the ankyrin 2.2 isoform was assembled in the
      retroviral vector, pG1. Murine erythroleukemia (MEL) cells, normal murine bone
      marrow cells, 3T3 fibroblasts, and nb/nb mutant bone marrow and spleen cells were
      transduced with the retroviral supernatant. Transduced mutant cells were induced
      to differentiate in liquid culture. Gene transfer was assessed by colony
      polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR,
      immunofluorescence, and Southern, Northern, and Western blot analysis. RESULTS:
      MEL cells, normal bone marrow progenitors, and nb/nb cells were all successfully
      transduced and expressed ankyrin by RT-PCR and Western blot. Transduced murine
      3T3 fibroblasts and MEL cells exhibited cell membrane staining by
      immunofluorescence. Colony RT-PCR demonstrated dependence of expression on
      erythropoietin. In vitro, the transduced nb/nb cells matured to
      polychromatophils, whereas nontransduced nb/nb cells matured to microspherocytes.
      CONCLUSION: Retroviral transfer of ankyrin corrected the defect leading to
      formation of microspherocytes in erythroid differentiation cultures from the
      nb/nb mutant. The human ankyrin promoter conferred erythropoietin-dependent
      expression in normal and mutant erythroid progenitors, which could have
      implications for the gene therapy of human hemolytic anemias.

PMID- 10907639
TI  - Transforming growth factor beta3 inhibits chronic myelogenous leukemia
      hematopoiesis by inducing Fas-independent apoptosis.
AB  - OBJECTIVE: Transforming growth factor beta3 (TGF-beta3) is a potent suppressor of
      human hematopoietic progenitor cells. In this article, we compare the activity of
      TGF-beta3 on highly purified CD34+ cells and more immature CD34-DR(-) cells from
      chronic myelogenous leukemia (CML) patients in chronic phase and normal donors.
      MATERIALS AND METHODS: Primitive hematopoietic progenitors were stimulated in
      liquid cultures and clonogenic assays by early-acting growth factors such as stem
      cell factor (SCF) and interleukin 11 (IL-11) and the intermediate-late-acting
      stimulating factors IL-3, granulocyte-macrophage colony-stimulating factor, and
      erythropoietin. Molecular analysis of bcr/abl mRNA was performed on single CML
      colonies by nested reverse transcriptase polymerase chain reaction. Moreover,
      cell cycle analysis and assessment of apoptosis of normal and leukemic CD34+
      cells were performed by propidium iodide (PI) alone and simultaneous staining
      with annexin V and PI, respectively. RESULTS: The colony-forming efficiency of
      CML CD34+ cells was generally inhibited by more than 90% regardless of whether
      the colony-stimulating factors were used alone or combined. When compared to
      normal CD34+ cells, leukemic cells were significantly more suppressed in 6 of 8
      culture conditions. The inhibitory effect of TGF-beta3 on CD34+ cells was exerted
      within the first 24 hours of incubation as demonstrated by short-term
      preincubation followed by IL-3-and SCF-stimulated colony assays. Evaluation of
      bcr/abl transcript on residual CML colonies incubated with TGF-beta3 demonstrated
      a small subset of neoplastic CD34+ cells unresponsive to the inhibitory effect of
      the study cytokine. TGF-beta3 demonstrated a greater inhibitory activity on
      primitive CD34+DR cells than on more mature CD34+ cells. Again, CML CD34+DR(-)
      cells were significantly more inhibited by TGF-beta3 than their normal
      counterparts in 3 of 8 culture conditions. Kinetic analysis performed on CD34+
      cells showed that TGF-beta induces cell cycle arrest in G(1) phase. However, this
      mechanism of action is shared by normal and leukemic cells. Conversely, TGF-beta3
      preferentially triggered the programmed cell death of CML CD34-cells without
      increasing the proportion of leukemic cells coexpressing CD95 (Fas receptor), and
      this effect was not reversed by functional blockade of Fas receptor. Conclusion.
      We demonstrate that TGF-beta3 exerts a potent suppressive effect on CML cells
      that is partly mediated by Fas-independent apoptosis.

PMID- 10907640
TI  - Activity of the caspase-3/CPP32 enzyme is increased in "early stage"
      myelodysplastic syndromes with excessive apoptosis, but caspase inhibition does
      not enhance colony formation in vitro.
AB  - OBJECTIVE: Excessive apoptosis may have a role in the ineffective hematopoiesis
      and cytopenias observed in myelodysplastic syndromes. The goals of this study
      were 1) to quantify apoptosis in patients with "early stage" myelodysplasia
      [including patients with refractory anemia (RA), RA with ringed sideroblasts
      (RARS), RA with excess blasts and with less than 10% blasts (RAEB(<10))], and in
      patients with "late stage" myelodysplasia [including RAEB with more than 10%
      blasts (RAEB(>10)), RAEB in transformation (RAEB-t), and acute myeloid leukemia
      secondary to myelodysplasia (LAM2)]; 2) to study the activation of the caspase
      3/CPP32 enzyme, a major "effector" caspase in hematopoiesis, in patients with
      "early stage" myelodysplasia, and 3) to evaluate the effect of caspase inhibition
      on the apoptotic phenotype and clonogenicity of hematopoietic progenitors in
      vitro in these patients. MATERIALS AND METHODS:  PATIENTS: Fifty-four patients
      with myelodysplastic syndromes, including 30 with "early stage" myelodysplasia
      and 24 with "late stage" myelodysplasia were studied. Study of apoptosis: TUNEL
      assay performed on bone marrow smears and/or quantification of annexin V positive
      bone marrow mononuclear cells by flow cytometric analysis. Caspacse-3/CPP32
      activity: Quantitative measurement of caspase-3/CPP32 activity on total bone
      marrow mononuclear cells using a fluorogenic substrate. Effect of the caspase
      inhibitor Z-VAD-FMK: 1) on the apoptotic phenotype of total bone marrow
      mononuclear cells and 2) on the clonogenicity of hematopoietic progenitor cells.
      RESULTS: The group of 30 patients with "early stage" myelodysplasia had
      statistically increased apoptosis compared to the group of 24 patients with "late
      stage" myelodysplasia (44.1% +/- 4.8 vs 21.8% +/- 3.6; p = 0.02) using the TDT
      mediated dUTP nick-end labeling (TUNEL) assay. In the group of patients with
      RAEB, those with MDS(RAEB<10) had excessive apoptosis compared to those with
      MDS(RAEB>10) (44.0% +/- 3.5% vs 29.5% +/- 3.6%;p = 0.042) The median caspase-3
      activity in 20 "early stage" myelodysplasia patients was 19,000 U (range 3,460
      41,000) and significantly increased compared to normal individuals (4,256 U,
      range 3,200-5,200; p = 0.032) Bone marrow mononuclear cells from 12 "early stage"
      MDS patients (including 11 from the 20 studied for caspase-3 activity) were
      incubated with or without the broad-spectrum caspase inhibitor Z-VAD-FMK. In 4 of
      9 evaluable patients (44.4%) with excessive apoptosis, the number of annexin V
      positive cells decreased in a dose-dependent manner in the presence of Z-VAD-FMK.
      However, in none of these patients was caspase inhibition with Z-VAD-FMK able to
      enhance colony formation in vitro. CONCLUSION: These results confirm that a major
      characteristic of patients with "early stage" myelodysplasia is increased
      apoptosis. The results also indicate that excessive apoptosis in these patients
      is accompanied by increased caspase-3/CPP32 activity. However, caspase inhibition
      with the broad-spectrum inhibitor Z-VAD-FMK cannot improve hematopoiesis in this
      group of patients, even when apoptosis is attenuated.

PMID- 10907641
TI  - Dominant expansion of human T cells in non-obese diabetic/severe combined
      immunodeficiency mice implanted with human bone fragments.
AB  - OBJECTIVE: To establish an in vivo animal model in which human T cells develop
      and function normally, a step toward developing new vaccines or chemical
      compounds that modulate immune functions and toward understanding T-cell immunity
      in humans. MATERIALS AND METHODS: Human bone fragments were implanted into non
      obese diabetes/severe combined immunodeficiency (NOD/SCID) mice. The presence of
      human blood cells in the peripheral blood of these mice was monitored
      periodically by immunostaining and fluorescence-activated cell sorting. RESULTS:
      After implantation of bone fragments, dominant expansion of human T lymphocytes,
      rather than myeloid and B cells, was observed over a 3-month period. In some
      cases, the proportion of human T cells rose to 40% of the peripheral blood
      mononuclear cells. These T cells showed CD4/CD8 ratios similar to those observed
      in human peripheral blood lymphocytes and had a broad repertoire of rearranged T
      cell receptor genes. Graft-versus-host reaction was not noted in any organ
      analyzed. To assess the suitability of NOD/SCID mice implanted with human bone
      fragments (hu-bone-NOD/SCID mice) as an in vivo model for HIV infection, the mice
      were infected with a T-lymphotropic strain of HIV-1 (NL4-3) at 7 weeks
      posttransplant. Serum p24 gag was detected at 2 weeks after inoculation, after
      which total CD4-positive cell numbers declined, as seen clinically in patients
      infected with HIV. CONCLUSION: Although the precise mechanism is yet to be
      determined by which predominant expansion of human T cells occurs in hu-bone
      NOD/SCID mice, such mice appear likely to serve as a useful and versatile model
      for studies involving human T-cell immunity.

PMID- 10907642
TI  - Functional conservation of platelet glycoprotein V promoter between mouse and
      human megakaryocytes.
AB  - OBJECTIVE: In an attempt to clarify the megakaryo-specific regulatory mechanism
      of GPV gene transcription, we characterized the 5'-flanking region of the mouse
      GPV gene. MATERIALS AND METHODS: The promotor activity of a -481/+22 5'-fragment
      of the mouse GPV gene was examined in normal mouse bone marrow cells (BMC) and
      various human cell lines using two distinct reporter gene assay systems,
      luciferase and green fluorescence protein (GFP). RESULTS: When a DNA construct
      consisting of this fragment and a GFP reporter gene were transiently expressed in
      thrombopoietin-supported mouse BMC culture, GFP was identified only in
      megakaryocytes. The same construct expressed high levels of GFP in the human
      megakaryocytic Dami line. When assessed by dual luciferase assay, the full 
      481/+22 fragment could drive variable promoter activity in human as well as mouse
      megakaryocytic lines but did not work in non-megakaryocytic cells. Sufficient
      transcriptional activation of this fragment was restricted to the cells
      expressing apparent GPV mRNA. A deletion and point mutation study indicated that
      GATA and Ets motifs, typical cis-acting elements for platelet-specific genes,
      located of -75 and -46, respectively, were essential for promoter function.
      CONCLUSION: The GPV promoter has the general characteristics found in platelet
      specific genes, and the mechanism for megakaryocyte-specific, maturation
      dependent regulation of GPV gene transcription is highly conserved between mouse
      and human. Analysis of GPV transcription mechanism utilizing human lines as well
      as BMC should provide new information on the final maturational process of
      megakaryocytes.

PMID- 10907643
TI  - Bone marrow accessory cells regulate human bone precursor cell development.
AB  - OBJECTIVE: Much remains to be learned about the intimate relationship between
      bone marrow and its surrounding tissue: the bone. We hypothesized that bone
      marrow accessory cell populations might regulate the development of human bone
      precursor cells. MATERIALS AND METHODS: We used immunologic phenotyping, and
      isolation methods to fractionate subpopulations of nonadherent, low-density
      (NALD) human bone marrow cells. These cells were examined for their ability to
      support the serum-free survival, proliferation, and expression of bone proteins
      by highly purified populations of human bone precursor cells. Quantitative
      assessment of the accessory cell populations as well as human bone precursor
      cells phenotype was performed using multiparameter flow cytometry. Bone protein
      expression was evaluated by immunocytochemistry, Western analysis, and enzymatic
      analysis (for alkaline phosphatase activity). RESULTS: Human bone marrow contains
      a cell population that stimulates the development of purified bone precursor
      cells. Feeder-layer studies demonstrate that these osteopoietic accessory cells
      (OACs) do not require cell-cell interaction to promote bone precursor cell
      development but, rather, produce soluble molecules responsible for their effects.
      Flow cytometric analyses reveal that bone marrow derived B cells, T cells,
      macrophages, natural killer cells, and endothelial cells do not produce this
      stimulatory factor. The (growth) factor cannot be replaced by addition of
      exogenous cytokines. The isolation of human transforming growth factor beta
      receptor type II (TGF-betaRII)-positive cells increases OAC-specific activity in
      bone cell ex vivo expansion cultures. Moreover, isolation of OAC bone marrow
      cells characterized by high TGF-betaRII expression, relatively low cellular
      complexity, and small size yields a population that is highly enriched for OACs.
      CONCLUSION: We conclude that human bone marrow contains a population of OACs that
      are an obligate requirement for the early phases of bone cell development ex
      vivo.

PMID- 10907644
TI  - All-trans-retinoic acid induces tyrosine phosphorylation of the CrkL adapter in
      acute promyelocytic leukemia cells.
AB  - OBJECTIVE: All-trans-retinoic acid (RA) is a potent inducer of differentiation of
      acute promyelocytic leukemia (APL) cells in vitro and in vivo. It also exhibits
      synergistic effects with interferons on the induction of differentiation and
      growth inhibition in vitro. Recent studies showed that interferons engage a
      signaling pathway involving the CBL proto-oncogene and the CrkL adapter, which
      mediates interferon-induced growth inhibitory signals. The objective of this
      study was to determine whether the CBL-CrkL pathway is activated by treatment of
      the NB-4 and HL-60 acute leukemia cell lines with RA. MATERIALS AND METHODS: The
      effects of RA treatment on CBL and CrkL phosphorylation, as well as on protein
      protein interactions, were determined in studies involving immunoprecipitations
      of cell extracts with specific antibodies and Western blots. In addition,
      glutathione-S-transferase fusion proteins were used in binding studies to
      determine whether the SH2 domain of CrkL interacts with CBL in a RA-dependent
      manner and whether Rapl is activated by RA. RESULTS: Treatment of NB-4 or HL-60
      cells with RA resulted in strong tyrosine phosphorylation of CBL, which was time
      and dose dependent. Similarly, RA induced tyrosine phosphorylation of the CrkL
      adapter and the association of CrkL with CBL. The RA-dependent interaction of
      CrkL with CBL was mediated by binding of the SH2 domain of CrkL to tyrosine
      phosphorylated CBL, suggesting that CBL provides a docking site for engagement of
      CrkL in a RA-activated cellular pathway. The guanine exchange factor C3G was
      found to be associated with CrkL at similar levels before and after RA treatment,
      but Rapl activation downstream of C3G was not inducible by RA. CONCLUSIONS: These
      findings demonstrate that the CBL-CrkL pathway is one of the mediators of the
      effects of RA on APL cells and suggest that one of the mechanisms of synergy
      between RA and interferons may involve regulation of components of this signaling
      cascade.

PMID- 10907645
TI  - Sequential requirements for SCL/tal-1, GATA-2, macrophage colony-stimulating
      factor, and osteoclast differentiation factor/osteoprotegerin ligand in
      osteoclast development.
AB  - OBJECTIVE: Osteoclasts are of hematopoietic origin. The mechanism by which
      hematopoietic stem cells are specified to the osteoclast lineage is unclear. To
      understand the process of generation and differentiation of this lineage of
      cells, we performed in vitro studies on the differentiation of embryonic stem
      cells. MATERIALS AND METHODS: We examined the potential of mutant embryonic stem
      cell lines harboring targeted deletions of the GATA-1, FOG, SCL/tal-1, or GATA-2
      genes to differentiate into osteoclasts and determined when these molecules
      function in osteoclast development. RESULTS: The lack of GATA-1 or FOG did not
      affect osteoclastogenesis. In contrast, SCL/tal-1-null embryonic stem cells
      generated no osteoclasts. In the case of the loss of GATA-2, a small number of
      osteoclasts were generated. GATA-2-null osteoclasts were morphologically normal
      and the terminal maturation was not disturbed, but a defect was observed in the
      generation of osteoclast progenitors. Experiments using specific inhibitors that
      block the signaling through macrophage colony-stimulating factor and osteoclast
      differentiation factor/osteoprotegerin ligand suggested that GATA-2 seems to act
      earlier in osteoclastogenesis than these cytokines. Interestingly, macrophage
      colony-forming units were not severely reduced by the loss of GATA-2 compared to
      osteoclast progenitors. CONCLUSION: These results indicate that osteocalsts need
      SCL/tal-1 at an early point in development, and that GATA-2 is required for
      generation of osteoclast progenitors but not for the later stages when macrophage
      colony-stimulating factor and osteoclast differentiation factor/ osteoprotegerin
      ligand are needed. We also demonstrated that osteoclast progenitors behave as a
      different population than macrophage colony-forming units.

PMID- 10907646
TI  - Cocultivation of umbilical cord blood cells with endothelial cells leads to
      extensive amplification of competent CD34+CD38- cells.
AB  - OBJECTIVE: In this report, methods to expand the number of human cord blood
      hematopoietic stem cells were explored. MATERIALS AND METHODS: CD34+ cord blood
      cells were expanded in the presence of various cytokine combinations in either a
      stroma-free cell culture system or a preformed porcine microvascular endothelial
      cell layer. After 7 to 21 days, stem cell number and function were monitored. In
      addition, the replicative history of stem cells was tracked using the fluorescent
      dye, PKH26. RESULTS: With the addition of various cytokine combinations, total
      cellular expansion was equivalent for both culture systems, although the
      endothelial cell-based system contained statistically greater numbers of CD34+
      cells. By day 21, the endothelial-based system receiving the FLT3L, SCF, IL-6,
      and GM-CSF cytokine combination contained five-fold greater numbers of CD34+ than
      the stroma cell-free culture cell system. Endothelial-based cultures receiving
      these four cytokines plus megakaryocyte growth and development factor produced a
      640-fold expansion of CD34+CD38- cells as compared to a four-fold expansion in
      the stroma-free system. The number of progenitor cells generated was similar with
      both systems, yet the greatest degree of expansion of cobblestone area-forming
      cells was observed in the endothelial based cultures (11-fold vs four-fold).
      Virtually all CD34+ and CD34+CD38+ cells expanded in the presence of endothelial
      cells had undergone self replication by day 10, yet stromal cell-free cultures
      contained a significant number (4.8%) of quiescent cells. Identical numbers of re
      isolated cord blood CD34+ cells expanded in both systems exhibited a similar
      ability to engraft and generate cells belonging to multiple hematopoietic
      lineages in human fetal bones implanted in immunodeficient mice. CONCLUSIONS:
      These results suggest that the use of preformed endothelial cell monolayers might
      permit the ex vivo generation of sufficient numbers of cord stem cells to serve
      as successful grafts for adult transplant recipients.

PMID- 10907647
TI  - Graft vs autoimmunity following allogeneic non-myeloablative blood stem cell
      transplantation in a patient with chronic myelogenous leukemia and severe
      systemic psoriasis and psoriatic polyarthritis.
AB  - OBJECTIVE: No specific therapy exists for autoimmune diseases caused by self
      reactive lymphocytes. As shown in experimental animals, which led to pilot
      clinical studies, elimination of self-reactive lymphocytes can be accomplished
      with high-dose chemoradiotherapy, followed by autologous stem cell
      transplantation, by re-establishment of unresponsiveness to self antigens of
      newly generated lymphocytes, due to a mechanism of central clonal deletion. We
      hypothesized that self-reactive lymphocytes causing autoimmune disease may be
      successfully eliminated by highly immunosuppressive yet not necessarily
      myeloablative conditioning in conjunction with allogeneic blood stem cell
      transplantation, since immunocompetent alloreactive lymphocytes of donor origin
      can effectively eliminate residual host-type hematopoietic cells, self-reactive
      lymphocytes included, by a mechanism that resembles graft-vs-leukemia (GVL)
      effects. The present report is an attempt to confirm the existence of graft-vs
      autoimmunity (GVA) effects in parallel with amplification of the alloreactive
      potential of donor lymphocytes following allogeneic non-myeloablative stem cell
      transplantation (NST). METHODS: We identified a patient with severe psoriatic
      arthritis who also had Philadelphia (bcr/abl) positive chronic myelogenous
      leukemia and therefore was fully eligible for NST. Both diseases responded
      initially to non-myeloablative conditioning involving fludarabine 30 mg/m2 x 6,
      anti-T-lymphocyte globulin 10 mg/kg X 4, and busulfan 4 mg/kg x 2. RESULTS: The
      initial NST procedure was uneventful and resulted in elimination of all signs of
      autoimmunity (psoriasis and arthritis). Recurrence of polyarthritis and
      exacerbation of psoriasis were observed in parallel with a significant increase
      in the proportion of male (host) DNA, and 5% of the mitoses were bcr/abl
      positive, indicating an increase in the clone of CML. Both bcr/abl-positive cells
      identified by RT-PCR and psoriatic arthritis were successfully eliminated
      following discontinuation of anti-GVHD prophylaxis with cyclosporine A (CSA),
      which resulted in activation of the alloreactive potential of donor T cells,
      accompanied by graft-vs-host disease (GVHD), suggesting the existence of GVA
      effects. RT-PCR for bcr/abl remains consistently negative for nearly 3 years, and
      all DNA remains donor type. CONCLUSIONS: The response of autoimmune disease
      manifestations to GVA effects in parallel with elimination of all host-derived
      hematopoietic cells supports our working hypothesis that autoimmune diseases
      caused by self-reactive lymphocytes may be effectively treated by elimination of
      alloreactive self-reactive lymphocytes following induction of host-vs-graft
      tolerance, in analogy with replacement of malignant or genetically abnormal host
      cells following DLI. It is therefore suggested that intentional GVA effects may
      be inducible by DLI following a conventional or preferably safer non
      myeloablative regimen in recipients with life-threatening autoimmune diseases
      resistant to conventional modalities. Adoptive immunotherapy of autoimmunity may
      thus involve a two-step procedure: first, inducing host-vs-graft and graft-vs
      host transplantation tolerance through a transient stage of mixed chimerism;
      second, inducing controlled GVA effects, initially by discontinuation of CSA and
      then, if indicated, by late outpatient DLI to eradicate residual hematopoietic
      cells of host origin.

PMID- 10907648
TI  - Transplantation with selected autologous peripheral blood CD34+Thy1+
      hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on
      engraftment, safety, and immune reconstitution.
AB  - OBJECTIVE: The aims of our study performed in myeloma were to evaluate the
      performance and the safety of Systemix's high-speed clinical cell sorter, to
      assess the safety and efficacy of deescalating cell dose cohorts of CD34+Thyl+
      hematopoietic stem cells (HSCs) as autologous grafts by determining engraftment,
      and to assess the residual tumor cell contamination using polymerase chain
      reaction (PCR) amplification assays of patient-specific complementarity
      determining region III (CDR III) analysis for residual myeloma cells. MATERIALS
      AND METHODS: The clinical trial was performed in 31 multiple myeloma patients,
      using purified human CD34+Thyl+ HSCs mobilized from peripheral blood with
      cyclosphosphamide and granulocyte-macrophage colony-stimulating factor to support
      a single transplant after high-dose melphalan 140 mg/m2 alone (cohort 1) and with
      total body irradiation (TBI) (cohorts 2-5) after an HSC transplant cell dose de
      escalation/escalation design. RESULTS: Twenty-three patients were transplanted.
      Engraftment data in the melphalan + TBI cohorts confirmed that HSC doses above
      the threshold dose of 0.8 x 10(6) CD34+Thy1+ HSCs/ kg provided prompt engraftment
      (absolute neutrophil count >0.5 x 10(9)/L day 10; platelet count >50 x 10(9)/L
      day 13). A higher rate of infections was observed in the early and late follow-up
      phases than usually reported after CD34+ selected or unselected autologous
      transplantation, which did not correlate with the CD34+Thy1+ HSC dose infused.
      Successful PCR for CDR III could only be performed in five patients on initial
      apheresis product and final CD34+Thy1+ HSC product and showed a median tumor log
      reduction >3.12. CONCLUSIONS: CD34+Thy1+ HSCs are markedly depleted or free of
      detectable tumor cells in multiple myeloma and are capable of producing fast and
      durable hematopoietic reconstitution at cell doses >0.8 x 10(6) CD34+Thy1+
      HSCs/kg. The delayed immune reconstitution observed is not different from that
      described in unselected autologous bone marrow and peripheral blood mononucleated
      cells transplants in multiple myeloma and may be corrected by addition of T cells
      either to the graft or to the patient in the posttransplant phase.

PMID- 10907649
TI  - Dynamic effects of self-efficacy on smoking lapse and relapse.
AB  - Self-efficacy (SE) is thought to be critical to success in smoking cessation both
      as an individual difference and as a dynamic process after a quit attempt. In
      this study, 214 smokers used palm-top computers to record day-to-day variations
      in SE during 4 weeks after quitting. SE remained at high and stable levels prior
      to a 1st lapse but decreased and became more variable thereafter. The authors
      used event history models with time-varying covariates to assess the effect of
      daily SE on lapse and relapse risk. Daily SE measures predicted an initial lapse
      on the subsequent day. However, this relationship was accounted for by stable
      baseline differences in SE (assessed by questionnaire), rather than by day-to-day
      dynamics in SE. Progression from 1st lapse to relapse was also examined. In this
      instance, daily SE predicted subsequent relapse risk, even when baseline SE and
      concurrent smoking were accounted for, suggesting the importance of SE dynamics
      for this stage of the relapse process.

PMID- 10907650
TI  - Postpartum return to smoking: staging a "suspended" behavior.
AB  - Two hundred fifty-six pregnant women who had quit smoking were classified into
      the precontemplation (PC), contemplation (C), preparation (PA), or action (A)
      stages of change for postpartum smoking cessation based on a 3-item algorithm
      assessing personal goals, self-efficacy, and smoking behavior. Logistic
      regression and event history analyses indicated group differences in return to
      smoking at 6 weeks and 3, 6, and 12 months postpartum. The percentage of women
      who returned to postpartum smoking was highest in the precontemplation stage and
      decreased with each subsequent stage, that is, at 6 weeks 83% of PCs, 64% of Cs,
      35% of PAs, and 24% of As had returned to smoking. Results lend support for the
      stages of change for postpartum smoking abstinence. Stage-based interventions may
      be developed to assist women in maintaining abstinence postpartum.

PMID- 10907651
TI  - Coping with neck and low back pain in the general population.
AB  - This study had 2 objectives: (a) to assess the psychometric properties of the
      Pain Management Inventory (PMI; G. K. Brown & P. M. Nicassio, 1987) with
      individuals in the general population with neck or low back pain, and (b) to
      assess the relationship between pain severity and coping. Data were taken from a
      mailed survey of a random sample of adults residing in Saskatchewan, Canada.
      Results validated the 2-factor structure of the PMI and provided evidence for the
      internal consistency of the coping subscales. Regression analyses revealed that
      passive coping was associated with being married, greater pain severity,
      depression, and poor health. Active coping was associated with female gender,
      higher education, less depression, good health, and frequent exercise. This study
      provides psychometric data to support the use of the PMI and information about
      factors associated with use of active and passive coping strategies in pain
      sufferers.

PMID- 10907652
TI  - Extending the activity restriction model of depressed affect: evidence from a
      sample of breast cancer patients.
AB  - Survey data from 95 women with Stage 1 (n = 36), Stage 2 (n = 49), or Stage 3 (n
      = 10) breast cancer both confirm and extend prior research indicating that
      restriction of normal activities is an important factor in depressed affect.
      Illness severity was directly related to more restricted routine activities, and
      more activity restriction was associated with higher public self-consciousness
      and less social support. Beyond the effects of age, self-consciousness, illness
      severity, and social support, activity restriction explained significant
      additional variance in symptoms of depression. Moreover, activity restriction
      mediated the impact of pain, public self-consciousness, and social support on
      depressed affect, which implies that these factors foster symptoms of depression
      by disrupting normal activities.

PMID- 10907653
TI  - Predicting change in depression following renal transplantation: effect of
      patient coping preferences.
AB  - Improvement in patient quality of life is a central goal of renal
      transplantation. This study examined the hypothesis that change in depression
      following transplantation would vary as a function of patient coping preferences.
      Sixty patients were assessed with the Krantz Health Opinion Survey and the Beck
      Depression Inventory while on the waiting list for a cadaveric renal transplant.
      Patients were reassessed approximately 12 months later. Among the 33 patients
      receiving a transplant during the follow-up period, those with a high preference
      for health-related information exhibited a substantial reduction in depression.
      In contrast, patients low in preference for information showed a slight increase
      in depression. Among the 27 patients who were not transplanted during the follow
      up period, preference for information had no effect on depression. Patient
      differences in preference for behavioral involvement did not exert a significant
      effect on depression.

PMID- 10907654
TI  - Personal and environmental factors associated with physical inactivity among
      different racial-ethnic groups of U.S. middle-aged and older-aged women.
AB  - Personal, program-based, and environmental barriers to physical activity were
      explored among a U.S. population-derived sample of 2,912 women 40 years of age
      and older. Factors significantly associated with inactivity included American
      Indian ethnicity, older age, less education, lack of energy, lack of hills in
      one's neighborhood, absence of enjoyable scenery, and infrequent observation of
      others exercising in one's neighborhood. For all ethnic subgroups, caregiving
      duties and lacking energy to exercise ranked among the top 4 most frequently
      reported barriers. Approximately 62% of respondents rated exercise on one's own
      with instruction as more appealing than undertaking exercise in an instructor-led
      group, regardless of ethnicity or current physical activity levels. The results
      underscore the importance of a multifaceted approach to understanding physical
      activity determinants in this understudied, high-risk population segment.

PMID- 10907655
TI  - Contributions of acute bouts of vigorous physical activity to explaining diurnal
      variations in feeling states in active, middle-aged women.
AB  - This study describes diurnal variations in feeling states in 84 women as a
      function of involvement in physical activity. Women completed feeling state
      checklists before and after bouts of vigorous physical activity that lasted a
      minimum of 20 min and on a stratified random-sampling protocol in response to a
      stimulus from an electronic pager. Participants self-reported the date, the time
      of day, the stimulus for responding, their current feeling states, and their
      ongoing activity. A total of 7,295 complete mood and activity reports were
      recorded in response to pager calls that were further coded into experience
      samplings that occurred on a nonexercise day, prior to exercise on an exercise
      day, and following exercise on an exercise day. Multilevel modeling analyses
      showed that in samplings recorded following exercise on exercise days, positive
      engagement, revitalization, and tranquility were elevated in comparison with
      predicted diurnal patterns.

PMID- 10907656
TI  - Studying intergenerational transmission of eating attitudes and behaviors:
      methodological and conceptual questions.
AB  - Associations between parent and child attitudes and behaviors related to eating
      and weight were examined among college-age men and women and their mothers and
      fathers (ns = 44, 47, 87, and 66, respectively). Parent attitudes and behaviors
      were assessed from the perspective of the parent and the student, and 2 pathways
      of influence were examined: modeling and direct criticism. In general, students'
      attitudes and behaviors were more strongly related to perceptions of their
      parents rather than to parents' own self-reports. There was more support for
      perceived direct criticism as a pathway of influence, particularly for daughters.
      Perceived criticism about eating and appearance had large associations with
      student attitudes and behaviors. Weight loss behavior was related to perceived
      criticism among daughters and to perceived paternal eating attitudes among sons.
      Results highlight important methodological and conceptual questions for
      intergenerational research.

PMID- 10907657
TI  - Vigilance, active coping, and cardiovascular reactivity during social interaction
      in young men.
AB  - This study of 72 undergraduate men examined the effects of two determinants of
      cardiovascular response-active coping and vigilance-on blood pressure and heart
      rate responses to social stressors. Observation of a future debate partner (i.e.,
      vigilance) evoked larger increases in blood pressure than did observation of a
      less relevant person, apparently through the combination of increases in cardiac
      output and vascular resistance. Preparation and enactment of efforts to exert
      social influence (i.e., active coping) evoked heightened blood pressure and heart
      rate responses through increased cardiac contractility and output. Thus, both
      vigilance and active coping in social contexts increased cardiovascular
      reactivity, but apparently through different psychophysiological processes.

PMID- 10907658
TI  - Serum lipids and their relationships with hostility and angry affect and
      behaviors in men.
AB  - Research into the relationship between the Type A behavior pattern and coronary
      heart disease suggests that the anger-hostility-aggression (AHA!) syndrome is
      directly related to total serum cholesterol and low-density lipoproteins. The
      present study involved an investigation of the specific components of the AHA!
      syndrome related to blood lipid levels in 98 healthy men. The disposition to
      experience and express anger when frustrated, criticized, or treated unfairly
      (angry reaction, a component of trait anger) was related to total serum
      cholesterol and to low-density lipoprotein levels. Age and diet also predicted
      levels of these lipids, but each was unrelated to angry reaction. These results
      suggest that in healthy men, the experience of strong angry affect in reaction to
      perceived rejection, criticism, or unfair treatment may be health-toxic because
      of its relationship to elevated unfavorable serum lipids.

PMID- 10907659
TI  - New concepts in cerebral palsy. Introduction.

PMID- 10907660
TI  - Other factors/conditions associated with cerebral palsy.
AB  - The cause for most cases of cerebral palsy is unknown. There are however, risk
      factors that have been associated with this chronic neuromuscular disease. The
      objective of this article is to review the maternal and fetal conditions (other
      than asphyxia and infection) strongly associated with increased rate of cerebral
      palsy. What remains to be elucidated is whether or not these associations are
      causative.

PMID- 10907661
TI  - Infection and cerebral palsy.
AB  - Recent data suggest a possible association of infection and cerebral palsy. The
      objective of this article is to examine the relationship between intrauterine
      infection, fetal infection, and long-term neurological dysfunction. In some
      children maternal infection is associated with brain white matter damage,
      periventricular leukomalacia, and cerebral palsy.

PMID- 10907662
TI  - Can neurological injury be timed?
AB  - Our knowledge about the cause of cerebral palsy continues to expand and prenatal
      events are thought to play an important role. This article reviews laboratory
      tests, imaging studies and pathologic findings that have been used to identify
      the timing of neurological injury. Limitations exist for all modalities, however,
      imaging studies, electroencephalograms and pathologic examination provide the
      most useful information. Improvements in our ability to time neurological injury
      will better direct our efforts to prevent cerebral palsy.

PMID- 10907663
TI  - Does asphyxia cause cerebral palsy?
AB  - The incidence of cerebral palsy is 1 per 1,000, whereas the proportion caused by
      perinatal asphyxia is only 8% to 10%. The purpose of this article is to review
      the relationship between asphyxia and cerebral palsy. Only a minority of cases,
      those involving severe pathological fetal academia, are consistently associated
      with neonatal encephalopathy and an increased risk of cerebral palsy.

PMID- 10907664
TI  - Fetal heart rate observations in the brain-damaged infant.
AB  - The objective of this study was to describe the fetal heart rate patterns and
      underlying pathophysiologic changes in the brain-damaged fetus. Fetuses with
      brain damage from hypoxic ischemic encephalopathy do not manifest uniform fetal
      heart rate patterns. However, these fetuses do show distinct fetal heart rate
      patterns that permit categorization based on their admission heart rate,
      subsequent changes in their baseline rate; and neonatal findings. Based on the
      observations of infants brain damaged in utero because of hypoxic ischemic
      encephalopathy, the intrapartum fetal management will depend on the admission
      fetal heart rate pattern, and the subsequent changes in the baseline rate.

PMID- 10907665
TI  - Effects of intra-accumbens injection of 2-methylthio ATP: a combined open field
      and electroencephalographic study in rats.
AB  - RATIONALE: Previous experiments have shown that P2 receptor activation increases
      the release of dopamine in the mesolimbic mesocortical system. OBJECTIVE: In
      order to investigate the functional correlates of dopaminergic stimulation, EEG
      and behavioural responses to injection of the P2 receptor agonist 2-methylthio
      ATP (2-MeSATP) into the nucleus accumbens (NAc) of rats were investigated.
      METHODS: EEG electrodes were positioned into the NAc together with the guide
      cannula for intracerebral injection. Behavioural analysis was performed in an
      open field cage and was evaluated by a video activity measurement system. Rats
      were assigned to separate groups that were given artificial cerebrospinal fluid
      (aCSF) or drug treatment. RESULTS: 2-MeSATP significantly extended the period of
      locomotor activity in the novel environment. The quantitative EEG was
      characterized by an elevation of the power in the alpha-range and a decrease in
      power in the delta range. The P2 receptor antagonists reactive blue 2 but not
      pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid (PPADS) also enhanced
      locomotion when given alone, and elevated the alpha-1 and beta-2 bands. Both
      antagonists abolished the locomotor and EEG responses to 2-MeSATP. The dopamine
      D1 receptor antagonist SCH 23390 and the D2/D3 receptor antagonist sulpiride did
      not alter locomotor activity when given either alone or in combination. Only
      sulpiride and especially sulpiride in combination with SCH 23390 prevented the
      effect of 2-MeSATP. Sulpiride produced a selective increase in the alpha-1 band
      of the power spectrum whereas SCH 23390 elevated the power of the alpha-1, alpha
      2 and beta-1 activities. Neither antagonist inhibited the effect of 2-MeSATP on
      the EEG when applied separately; however, the co-administration of SCH 23390 and
      sulpiride abolished the 2-MeSATP-induced alteration of power distribution. After
      a 6-hydroxydopamine (6-OHDA)-induced lesion of the accumbal dopaminergic
      terminals, 2-MeSATP failed to enhance the locomotor activity and to induce the
      characteristic EEG changes. CONCLUSIONS: The observed alterations in open field
      behaviour and quantitative EEG after injection of 2-MeSATP into the NAc may be
      mostly due to P2 receptor-mediated dopamine release and subsequent receptor
      activation.

PMID- 10907666
TI  - Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and
      sertindole in vivo: a [123I]epidepride single photon emission tomography (SPET)
      study.
AB  - RATIONALE: Previous work suggests clozapine preferentially targets limbic
      cortical dopamine systems, which could help account for its lack of
      extrapyramidal side effects (EPS) and superior therapeutic efficacy. OBJECTIVES:
      To test the hypothesis that olanzapine, a novel atypical antipsychotic drug,
      occupies temporal cortical D2/D3 receptors to a greater extent than striatal
      D2/D3 receptors in vivo. METHODS: Nine schizophrenic patients taking either
      olanzapine [(n=5; mean (SD) age: 32.5 (6.5) years; daily dose: 18.3 (2.6) mg] or
      sertindole [(n=4; mean (SD) age: 30.3 (7.4) years; daily dose: 16 (5.6) mg] were
      studied with [123I]epidepride ((S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3
      dimethoxybenz amide) and single photon emission tomography (SPET). An estimate of
      [123I]epidepride 'specific binding' to D2/D3 receptors was obtained in patients
      and age-matched healthy volunteers. A summary measure was generated representing
      striatal and temporal cortical relative %D2/D3 receptor occupancy by
      antipsychotic drugs. Occupancy data were compared with previously studied groups
      of patients receiving typical antipsychotic drugs (n=12) and clozapine (n=10).
      RESULTS: Mean striatal and temporal cortical %D2/D3 receptor occupancy in
      olanzapine-treated patients was 41.3% (SD 17.9) and 82.8% (SD 4.2), respectively.
      Unexpectedly low levels of striatal relative %D2/D3 receptor occupancy were seen
      in two patients with typical antipsychotic-drug-induced movement disorder prior
      to switching to olanzapine. In the temporal cortex, mean D2/D3 dopamine receptor
      occupancy levels above 80% were seen for all antipsychotic drugs studied.
      CONCLUSIONS: The atypical antipsychotic drugs olanzapine and sertindole, in
      common with clozapine, demonstrate higher occupancy of temporal cortical than
      striatal D2/D3 dopamine receptors in vivo at clinically useful doses. This could
      help mediate their atypical clinical profile of therapeutic efficacy with few
      extrapyramidal side effects. Limbic selective blockade of D2/D3 dopamine
      receptors could be a common action of atypical antipsychotic drugs.

PMID- 10907667
TI  - Attenuation of the bidirectional effects of chlordiazepoxide and FG 7142 on
      conditioned response suppression and associated cardiovascular reactivity by loss
      of cortical cholinergic inputs.
AB  - RATIONALE: Basal forebrain cortical cholinergic projections have been
      hypothesized to mediate the enhanced cardiovascular defensive response initiated
      by the putative anxiogenic benzodiazepine receptor (BZR) partial inverse agonist
      FG 7142 (FG). The present study was designed to test the broader hypothesis that
      the integrity of this cholinergic projection is required for the mediation of the
      bidirectional modulatory effects of BZR agonists and inverse agonists on anxiety
      and associated cardiovascular reactivity. OBJECTIVES: The interactions between
      the effects of 192 IgG-saporin-induced lesions of basal forebrain corticopetal
      cholinergic neurons and of the BZR agonist chlordiazepoxide (CDP) and FG on the
      performance of rats tested in a conditioned suppression paradigm and on
      associated cardiovascular reactivity were assessed. METHODS: Lesioned and control
      animals were equipped with a telemetric device to record heart rate, trained in
      an operant lever task, and then tested for suppression of responding during
      presentation of a conditioned stimulus (CS) and a general contextual cue that was
      previously associated with shock. FG, CDP (8 mg/kg) and vehicle were administered
      IP in separate extinction sessions. RESULTS: In control animals, operant
      responding was suppressed during presentation of the CS and contextual cue.
      Administration of FG enhanced this suppression, while CDP attenuated it. Lesions
      attenuated overall response suppression as well as the modulatory effects of BZR
      ligands on responding during presentation of the contextual stimulus. Likewise,
      lesions attenuated the cardioacceleratory response to the contextual stimulus and
      the ability of the BZR ligands to modulate this response. CONCLUSIONS: The
      behavioral and autonomic responses to anxiety-related stimuli, as well as the
      modulatory effects of BZR ligands, are mediated in part via cortical cholinergic
      inputs.

PMID- 10907668
TI  - Increased sensitivity to alprazolam in females with a paternal history of
      alcoholism.
AB  - RATIONALE: Few studies have directly examined the effects of benzodiazepines in
      individuals with a family history of alcoholism, particularly women, to determine
      whether they are differentially sensitive to their effects. OBJECTIVES: To
      determine whether females with a confirmed paternal history of alcoholism (FHP;
      n=14) were differentially sensitive to the mood and performance effects of
      alprazolam and buspirone compared with females without a first-degree family
      history of alcoholism (FHN; n=14). METHODS: The acute effects of placebo,
      alprazolam (0.25, 0.50, 0.75 mg), and buspirone (5, 10, 15 mg) were evaluated
      using a double-blind, placebo-controlled outpatient design. Drug effects were
      assessed using performance tasks, observer ratings of drug effect, and subjective
      ratings of mood, drug strength, and drug liking. RESULTS: Alprazolam impaired
      performance in a dose-related manner on all performance tasks for both groups of
      females, whereas buspirone had minimal effects on performance. The highest dose
      of alprazolam impaired the response to the digit symbol substitution test (DSST),
      digit recall, and word memory more in FHP females than in FHN females. Further,
      performance on the DSST and immediate word recall was able to accurately predict
      family history status. Correspondingly, FHP women reported greater increases in
      "difficulty concentrating" and "unmotivated" and greater decreases in items such
      as positive mood following alprazolam than FHN women. In contrast, alprazolam
      produced similar dose-related increases in subject-rated and observer-rated drug
      strength ratings in both groups of females. Lastly, there was no evidence of an
      increase in ratings of drug liking in either group following alprazolam.
      CONCLUSIONS: In contrast to many previous findings with FHP males, these results
      suggest that FHP females may be more sensitive to the performance-impairing
      effects and negative subjective effects of alprazolam.

PMID- 10907669
TI  - Effects of phencyclidine on behavior and extracellular levels of dopamine and its
      metabolites in neonatal ventral hippocampal damaged rats.
AB  - RATIONALE: The use of neonatal hippocampal lesioned rats is well established in
      animal models of schizophrenia. Moreover, the dysfunction of N-methyl-D-aspartate
      (NMDA) neurotransmission may play a crucial role in the pathophysiology of
      schizophrenia. OBJECTIVE: To examine the role of NMDA neurotransmission in the
      neonatal ventral hippocampal damaged rat. METHODS: In initial experiments, we
      compared the effects of mild environmental stress (HAB) and the injection of
      saline and methamphetamine (MAP, 1.5 mg/kg, IP) in lesioned and sham-operated
      rats. We also examined the effects of a single injection of phencyclidine (PCP,
      10 mg/kg, IP) on locomotor activity and extracellular levels of dopamine (DA) and
      its metabolites in the nucleus accumbens (NAc) of lesioned and sham-operated rats
      using an in vivo brain microdialysis method. RESULTS: Compared with sham-operated
      controls, the lesioned rats showed increased locomotor activity at postnatal day
      56 (PD56) but not at PD35 after HAB and MAP administration. Similarly, the
      lesioned rats showed increased locomotor activity at PD56 but not at PD35 after
      PCP administration. Unexpectedly, the increase in DA levels was significantly
      greater in the sham-operated rats than in the lesioned rats. CONCLUSIONS: The
      results suggest that neonatal hippocampal lesioned rats are accompanied by the
      dysfunction of NMDA neurotransmission. They also suggest that hyperresponsiveness
      to PCP following neonatal hippocampal lesions does not depend on the
      extracellular DA concentration in the NAc.

PMID- 10907670
TI  - The effect of d-amphetamine on performance on two operant timing schedules.
AB  - RATIONALE: Previous experiments have shown that d-amphetamine disrupts timing
      behaviour in rats. It has been proposed that d-amphetamine's effects reflect a
      reduction in the period of the pacemaker of the hypothetical internal clock.
      However, some studies have obtained conflicting results. OBJECTIVE: To examine
      the effects of d-amphetamine (0.2, 0.4, 0.8 mg kg(-1) i.p.) on performance on two
      quantitative timing schedules: a free-operant schedule, in which rats were
      trained to distribute their responses differentially between two levers during
      the course of a 50-s trial (free-operant psychophysical procedure), and a
      discrete-trials schedule, in which rats were trained to discriminate the duration
      of light stimuli (interval bisection task). METHODS: In experiment 1, rats were
      trained under the free-operant psychophysical procedure to respond on two levers
      (A and B) in 50-s trials in which reinforcement was provided intermittently for
      responding on A during the first half and on B during the second half of the
      trial. For one group, repetitive switching between levers was permitted; for
      another group, it was prevented. In experiment 2, rats were exposed to press
      lever A after a 2-s stimulus and lever B after an 8-s stimulus, and were then
      tested with stimuli of intermediate duration. For one group, a 'poke response'
      (depression of a central tray flap) was required after stimulus presentation to
      effect lever presentation; for the other group, this requirement did not operate.
      In both experiments, quantitative indices of timing were derived from the
      psychophysical functions (%B responding vs time). RESULTS: In experiment 1, d
      amphetamine increased the Weber fraction and displaced the psychophysical curve
      to the left in both versions of the schedule, as well as producing rate-dependent
      suppression of responding. In experiment 2, d-amphetamine increased the Weber
      fraction in both versions of the task without displacing the curve. CONCLUSIONS:
      These results confirm the disruptive effect of d-amphetamine on timing. The
      results of experiment 1 are consistent with the proposal that the drug reduces
      the period of the hypothetical pacemaker. However, the results of experiment 2 do
      not support this suggestion. Taken together, the results support the notion that
      different neural mechanisms may be involved in timing tasks involving temporal
      distribution of responding and discrimination of the duration of exteroceptive
      stimuli.

PMID- 10907671
TI  - Effects of repeated ingestion of grapefruit juice on the single and multiple oral
      dose pharmacokinetics and pharmacodynamics of alprazolam.
AB  - The effects of repeated ingestion of grapefruit juice, an inhibitor of cytochrome
      P450 3A4 (CYP3A4), on the pharmacokinetics and pharmacodynamics of both single
      and multiple oral doses of alprazolam, a substrate of CYP3A4, were examined. In
      study 1, eight healthy volunteers ingesting 600 ml/day water or grapefruit juice
      for 10 days took a single oral 0.8-mg dose of alprazolam on the eighth day.
      Plasma drug concentrations were monitored up to 48 h after alprazolam dosing
      together with evaluation of psychomotor function. Grapefruit juice altered
      neither the plasma concentrations of alprazolam at any time points, any
      pharmacokinetic parameters, nor the majority of psychomotor function parameters
      in subjects. In study 2, 11 patients with anxiety disorders receiving alprazolam
      (0.8-2.4 mg/day) ingested grapefruit juice (600 ml/day) for 7 days. Blood samples
      were collected before and during grapefruit juice ingestion and 1 week after its
      discontinuation together with an assessment of clinical status. Grapefruit juice
      altered neither the steady-state plasma concentration of alprazolam nor the
      clinical status in patients. The present study shows that grapefruit juice is
      unlikely to affect pharmacokinetics or pharmacodynamics of alprazolam due to its
      high bioavailability.

PMID- 10907673
TI  - The 5-HT3 agent N-(3-chlorophenyl)guanidine (MD-354) serves as a discriminative
      stimulus in rats and displays partial agonist character in a shrew emesis assay.
AB  - RATIONALE: There is some, albeit conflicting, evidence that 5-HT3 receptors might
      be involved in the actions of abused stimulants. Most studies have focussed on
      examinations of 5-HT3 antagonists; this might be due to a lack of high-affinity 5
      HT3 agonists that readily penetrate the blood-brain barrier. OBJECTIVES: N-(3
      Chlorophenyl) guanidine (MD-354) is a member of a novel class of 5-HT3 ligands
      developed in our laboratories. We have previously demonstrated that MD-354 can
      exert agonist effects and now further explore this action. METHODS: Rats (n=9)
      were trained to discriminate 2 mg/kg MD-354 from saline vehicle in a two-lever
      drug discrimination task (VI-15 s schedule of reinforcement). The actions of
      agents with 5-HT3 character were evaluated. The emetic and antiemetic actions of
      MD-354 were also examined using the shrew as test subject. RESULTS: Various
      agents with demonstrated 5-HT3 agonist properties substituted for the MD-354
      stimulus (MD-354 ED50=0.5 mg/kg): quipazine (ED50=0.2 mg/kg), meta
      chlorophenylbiguanide (mCPBG, ED50=1.4 mg/kg), 2-methyl 5-HT (ED50=4.5 mg/kg), 1
      (2-naphthyl)biguanide (2-NBG, ED50=1.9 mg/kg), and N-(2-naphthyl)guanidine (2-NG,
      ED50=0.7 mg/kg). Administration of the training dose of MD-354 in combination
      with the 5-HT3 antagonists zacopride and tropisetron resulted in stimulus
      antagonism (AD50=0.02 mg/kg); administered alone, however, zacopride engendered
      81% MD-354-appropriate responding (ED50=0.03 mg/kg). MD-354 was shown to produce
      an emetic effect in the shrew at very high doses (i.e., 40 mg/kg); however, when
      administered in combination with cisplatin, MD-354 behaved as an antiemetic agent
      at 10 mg/kg. CONCLUSION: Taken together, the results indicate that MD-354 is a 5
      HT3 agonist and that it might be an agent with partial agonist activity.

PMID- 10907672
TI  - Cocaine-like discriminative stimulus effects of heroin in squirrel monkeys: role
      of active metabolites and opioid receptor mechanisms.
AB  - RATIONALE AND OBJECTIVES: Opioid agonists frequently have been reported to share
      discriminative stimulus (DS) effects with cocaine; however, the pharmacological
      basis of these shared effects is not understood completely. The present study
      assessed the ability of heroin and its deacetylated metabolites, 6
      monoacetylmorphine (6-MAM) and morphine, to engender cocaine-like DS effects and
      investigated the role of opioid receptor subtypes in modulating these DS effects.
      METHODS: Squirrel monkeys were trained to discriminate 0.3 mg/kg cocaine (i.m.)
      from vehicle under a 10-response fixed-ratio schedule of food reinforcement, and
      responding on the drug lever was assessed after varying i.m. doses of heroin, 6
      MAM, and morphine. The potential role of opioid receptor mechanisms in modulating
      the cocaine-like DS effects of heroin and its metabolites was assessed with the
      mixed mu/kappa opioid antagonist naltrexone, the delta-selective antagonist
      naltrindole, and the kappa-selective antagonist nor-binaltorphimine. RESULTS:
      Heroin, 6-MAM, and morphine engendered dose-related increases in responding on
      the cocaine lever in three of four monkeys. Naltrexone shifted the dose-response
      functions for heroin and its metabolites to the right, and in vivo apparent pA2
      analyses revealed that naltrexone antagonized the effects of the opioids in a
      manner consistent with mu receptor antagonism (apparent pA2 values ranging from
      8.20 to 8.47). Naltrindole only minimally altered the dose-response functions of
      heroin, 6-MAM, and morphine, whereas nor-binaltorphimine did not block the
      cocaine-like DS effects of the three opioid agonists, suggesting that neither
      delta nor kappa receptors played a prominent role in the cocaine-like DS effects
      of heroin and its metabolites. CONCLUSIONS: These results suggest that heroin and
      its deacetylated metabolites engendered cocaine-like DS effects in a similar
      fashion. Furthermore, the cocaine-like DS effects of these opioids were modulated
      by a predominantly mu-opioid receptor mechanism.

PMID- 10907674
TI  - Expression of flavour preferences conditioned by caffeine is dependent on
      caffeine deprivation state.
AB  - RATIONALE: The acquisition of a caffeine conditioned flavour preference depends
      on the caffeine deprivation status of subjects during conditioning. It is not
      known if the expression of an established flavour preference is also state
      dependent. OBJECTIVES: To determine if the expression of a flavour preference
      conditioned by caffeine is dependent on the level of deprivation at the time of
      testing. METHODS: In a double-blind placebo controlled study, 44 subjects were
      given 4 days exposure to a novel flavoured drink following overnight abstinence
      from caffeine. Half the subjects received caffeine (100 mg) in the drink, while
      the remainder had placebo (maltodextrin, 100 mg). Subjects rated the pleasantness
      of the drink each time. On a fifth (test) day, the subjects were given additional
      caffeine (100 mg) or placebo 2 h before consuming and rating the pleasantness of
      the drink. RESULTS: Pleasantness ratings for the novel drink increased over the 4
      conditioning days in subjects receiving caffeine, but decreased in those given
      placebo. On day 5, subjects who were trained and tested in the same caffeine
      deprivation state expressed pleasantness ratings similar to those for the final
      training day. In contrast, subjects who were trained and tested in different
      states expressed pleasantness ratings that were significantly different from
      those of the final training day. CONCLUSIONS: These results suggest that the
      expression of caffeine conditioned flavour preferences are acutely sensitive to
      current motivational state, and a number of possible explanations are discussed.

PMID- 10907675
TI  - Electroencephalogram alterations during treatment with olanzapine.
AB  - RATIONALE: Olanzapine is similar in structure and pharmacology to clozapine. An
      increased incidence of electroencephalogram (EEG) abnormalities and seizures has
      been associated with clozapine but not with olanzapine, although isolated cases
      of seizures under olanzapine have been observed in high-risk patients. OBJECTIVE:
      To evaluate the frequency of epileptic and non-epileptiform EEG abnormalities
      during treatment with olanzapine. METHODS: Using a rating scale of demonstrated
      reliability, 43 EEGs of patients receiving 10-25 mg/day olanzapine in routine
      treatment were blindly rated and compared with EEG registrations from the same 43
      patients with a different medication. RESULTS: There was no difference in
      epileptiform activity between the conditions with and without olanzapine.
      However, EEG slowing was significantly more frequent with olanzapine than under
      the other condition. This difference could not be attributed to concomitant
      medication. CONCLUSIONS: Although epileptiform activity did not increase under
      olanzapine, unspecific EEG abnormalities may be more frequent than with use of
      other neuroleptics. Careful surveillance of patients with risk factors for
      seizures is advisable. Further studies addressing the frequency and clinical
      relevance of EEG changes under olanzapine are necessary.

PMID- 10907676
TI  - The effects of an oral multivitamin combination with calcium, magnesium, and zinc
      on psychological well-being in healthy young male volunteers: a double-blind
      placebo-controlled trial.
AB  - RATIONALE: Vitamin and mineral supplements may be associated with improved
      psychological status. OBJECTIVE: The present study tested the effects of a
      multivitamin and mineral supplement (Berocca) on psychological well-being.
      METHODS: In a double-blind randomised-control trial, 80 healthy male volunteers
      were assigned to either Berocca or placebo. Questionnaires measuring
      psychological state were completed and a blood sample taken to determine plasma
      zinc concentration on day 1 (pre-treatment) and again on day 28 (post-treatment),
      following 28 days of treatments, which were administered at a dosage of one
      tablet daily. At the end of the study, the acceptability of the treatment and
      participants' awareness of treatment condition were assessed, as was habitual
      dietary behaviour. RESULTS: Relative to placebo, treatment with Berocca was
      associated with consistent and statistically significant reductions in anxiety
      and perceived stress. Participants in the Berocca group also tended to rate
      themselves as less tired and better able to concentrate following treatment. In
      addition, participants registered more somatic symptoms following placebo than
      following Berocca. These effects cannot be attributed to differences in the
      acceptability of the two treatments or to participants guessing what treatment
      they received. CONCLUSION: These findings demonstrate that Berocca significantly
      reduces anxiety and perceived stress.

PMID- 10907677
TI  - Restoration of latent inhibition by olanzapine but not haloperidol in entorhinal
      cortex-lesioned rats.
AB  - RATIONALE: Latent inhibition (LI) refers to the decrease in conditioned response
      induced by the repeated non-reinforced pre-exposure to the conditioned stimulus
      before its pairing with the unconditioned stimulus during the conditioning stage.
      LI has been considered as a relevant animal model for the study of the biological
      bases of schizophrenia. LI has recently been demonstrated to depend on the
      integrity of the entorhinal cortex, as lesioning of this area disrupted LI.
      OBJECTIVES: The present study aimed to verify whether the classical neuroleptic
      haloperidol and/or the atypical antipsychotic olanzapine would prevent the effect
      of entorhinal cortex lesioning. METHODS: LI was studied in an off-baseline
      conditioned emotional response (CER) paradigm in which a tone is paired with a
      footshock. Entorhinal cortex lesions were produced by the electrolytic method.
      After a recovery period, both lesioned and control rats received either
      haloperidol (0.3 mg/kg), olanzapine (0.3 mg/kg) or vehicle before both the pre
      exposure and conditioning stages of the experiment. RESULTS: In control rats, pre
      exposure to the tone induced LI, which was affected by neither haloperidol nor
      olanzapine. Lesioning of the entorhinal cortex produced a deficit of LI, which
      was restored by olanzapine but not by haloperidol. CONCLUSIONS: This result
      suggests a dissociation of the anatomical and pharmacological targets of the two
      drugs. The possible involvement of dopamine D3 receptors in the effects of
      olanzapine is discussed.

PMID- 10907678
TI  - The alpha4beta2 agonist SIB 1765F, but not the alpha7 agonist AR-R 17779, cross
      sensitises to the psychostimulant effects of nicotine.
AB  - RATIONALE: Repeated administration of nicotine leads to an augmentation of its
      locomotor activating effects. Although studies have begun to identify the
      nicotinic receptor subtype(s) mediating the psychostimulant properties of
      nicotine, none as yet have investigated the subtypes which contribute to the
      process of sensitisation. OBJECTIVES: We therefore investigated cross
      sensitisation to nicotine using subjects chronically treated with two nicotine
      subtype-selective agonists in an attempt to identify the relative contribution of
      each to the sensitisation process. METHODS: Rats received ten daily injections of
      either vehicle, nicotine (0.4 mg/kg), the alpha7-agonist AR-R 17779 (20 mg/kg),
      or the alpha4beta2-agonist SIB 1765F (3 mg/kg), and their subsequent locomotor
      response to acute challenge with each of these compounds was assessed. RESULTS:
      Chronic administration of both nicotine and SIB 1765F, but not AR-R 17779,
      resulted in an enhanced locomotor response to acute challenge with either
      nicotine or SIB 1765F but not AR-R 17779. CONCLUSIONS: These data support a role
      for the alpha4beta2 receptor in both the initiation and expression of
      sensitisation to the psychomotor stimulant effects of nicotine.

PMID- 10907679
TI  - The kinetics of Langerhans cells in equine insect hypersensitivity "Kasen".
AB  - An immunohistochemical study was carried out on the kinetics of Langerhans cells
      (LCs) at various pathological stages of "Kasen". Skin lesions of "Kasen" that
      were collected by biopsy from May to October were classified histopathologically
      into three stages: initial (Group I, 31 cases), developing (Group II, 50 cases)
      and regressing (Group III, 13 cases). LCs showed a positive reaction with anti
      equine thymocytes (EqT6) monoclonal antibody (MoAb) and anti-major
      histocompatibility complex (MHC) class II MoAb by immunohistochemical staining.
      The anti-EqT6 MoAb was intensely positive along the cytoplasmic process. The
      number of LCs per unit area increased markedly with the passage of time from the
      initial to the developing stage of the disease, particularly in the epidermo
      dermal junction (EDJ). However, the number of LCs tended to decrease in the
      epidermal layer. In conclusion, the LCs moving into the epidermal layer moved
      into the EDJ and dermis during the time course of lesion development, and the
      changes occurring in LCs possibly influenced the progression of the skin lesions
      of "Kasen".

PMID- 10907680
TI  - Chronological recognition by chicken of antigenic polypeptides in Salmonella
      enteritidis with different plasmid profiles: relationship to infection rate.
AB  - The antigenic polypeptides in Salmonella Enteritidis (SE) were chronologically
      recognized by the chicken immune system, using Western immunoblotting. Broiler
      chicks challenged at three days of age with SE strain carrying the most prevalent
      plasmid profile of 14.1 and about (approximately) 50 kb were bled at 17, 24, 31,
      38 and 45 days of age. Pooled sera of blood collected at each age was reacted by
      Western immunoblotting with banded polypeptides of three predominant SE strains
      that acquired the following respective plasmid profiles: 14.1 kb; 14.1 and
      approximately 50.0 kb; and 1.8, 14.1 and approximately 50.0 kb. The immunoblots
      of each pooled sera collected at a specific age against the three SE strains were
      similar. More specifically, the early immune response at 17 days of age had
      antibodies recognizing only one polypeptide in the three SE strains namely, the
      35.8 kDa. At 24 or 31 days of age, the acquired immunity to infection had
      antibodies recognizing five similar polypeptides in the three SE strains namely,
      the 14.4 (fimbriae protein), 21.5 (fimbriae protein), 30.5, 35.8, and 66.2 kDa.
      At 38 and 45 days of age, the antibodies recognized additional polypeptides
      namely, the 41.5 and 55.6 kDa, respectively. The recognition of the 41.5 and 55.6
      kDa polypeptides at 45 days of age was associated with higher invasiveness of SE
      to spleens and livers (15.6%) and in higher cecal colonization (59.4%) in
      comparison to absence of recognition to the two polypeptides at 31 days of age
      associated with low infectivity to spleens (0%), livers (3.1%), and ceca (9.4%).

PMID- 10907681
TI  - Relation between antigen release and immune response of oil adjuvanted vaccines
      in chickens.
AB  - The relationship between release properties of the model antigen, bovine serum
      albumin (BSA), from formulations in vitro and immune response after
      administration of various oil adjuvanted vaccines containing liquid paraffin was
      examined in chickens. The vaccine prepared at an hydrophile-lipophile-balance
      (HLB) number of 4.8 showed slower release of BSA and higher immune response on
      injected chickens than that with an HLB number of 6.0. Decreases of aqueous
      volume ratio in the formulation also led to slower release of BSA and higher
      immune response. The slower release rate of BSA showed higher ELISA antibody
      titer even at 20 weeks after vaccination. The ELISA antibody titer inversely was
      related to the constant release rate, k, calculated from the in vitro release
      test. The correlation coefficient was 0.863. The immune response of oil
      adjuvanted vaccines containing Haemophilus paragallinarum agreed well with these
      results with BSA. Our results indicated that a stronger and more prolonged immune
      response of oil adjuvanted vaccines was achieved by slower release rate of
      antigen from the formulation. In addition, there was a good correlation between
      immune response and the value of k.

PMID- 10907682
TI  - Effect of glycosylation and glucose trimming inhibitors on the influenza A virus
      glycoproteins.
AB  - N-glycosylation and glucose trimming of the influenza virus hemagglutinin (HA)
      and neuraminidase (NA) were studied by using glycosylation inhibitor
      (tunicamycin; TM) and glucosidase inhibitors. TM treatment of MDCK cells infected
      with a reassortant virus NWS-N8 resulted in reduced transport of the viral
      glycoproteins to the cell surface. The degree of the effects differed between the
      HA and the NA (80% reduction for the HA and 97% reduction for the NA), indicating
      a difference in dependency on N-glycosylation between these glycoproteins.
      Differential dependency on glucose trimming was clearly demonstrated when the
      surface transport of the glycoproteins was compared after treatment of the virus
      infected cells with glucosidase inhibitors. Fluorescence-activated cell sorting
      (FACS) analysis revealed that the surface transport of the NA reduced to 50%
      after castanospermine (CST) treatment but not did that of the HA. An anti-viral
      effect of a glucosidase inhibitor on the NWS-N8 strain was also demonstrated. The
      correlation between the expression of the NA on the cell surface and virus yield
      suggests that CST may interfere with virus release through its effect on the NA.

PMID- 10907683
TI  - Effects of in vivo administration of anti-IL-10 or anti-IFN-gamma monoclonal
      antibody on the host defense mechanism against Plasmodium yoelii yoelii
      infection.
AB  - Our previous reports indicated that C57BL/6 mice infected with a lethal variant
      of Plasmodium yoelii 17X (P. yoelii 17XL) produced high levels of interleukin 10
      (IL-10) and interferon-gamma (IFN-gamma) while mice infected with the nonlethal
      variant of the parasite did not produce detectable levels of IL-10. In the
      present study, the involvement of IL-10 and IFN-gamma in exacerbation or
      regulation of blood-stage malaria was investigated by using the lethal variant of
      P. yoelii 17XL and monoclonal antibodies (mAb) against the cytokines. C57BL/6
      mice were injected intraperitoneally with a neutralizing anti-IL-10 mAb or anti
      IFN-gamma mAb after inoculation with P. yoelii 17XL. Treatment of mice with anti
      IL-10 mAb resulted in substantial prolongation of survival and 60% of treated
      mice survived while 100% of control mice died by day 11. On the contrary,
      treatment of mice with anti-IFN-gamma mAb exacerbated infection and all mice died
      after an earlier period than those treated with normal rat Ig. No differences in
      parasitemias were found between treated and untreated mice. To elucidate the
      involvement of nitric oxide in the host protection or exacerbation, mice were
      treated with aminoguanidine, an inhibitor of nitric oxide synthetase, after
      inoculation of P. yoelii 17XL. Neither mortality nor parasitemia was influenced
      by the treatment. These results indicate that an IFN-gamma response is associated
      with protective immunity in mice infected with P. yoelii 17XL, while an IL-10
      response is associated with disease exacerbation during the infection.

PMID- 10907685
TI  - Innervation pattern of substance P- and calcitonin gene-related peptide
      immunoreactive nerves of the cerebral arteries in the quail.
AB  - The pattern of cerebrovascular substance P (SP)- and calcitonin gene-related
      peptide (CGRP)-immunoreactive (IR) innervation was investigated in the quail. SP-
      and CGRP-IR nerves were relatively a few in the rostral part of the anterior
      circulation, and very scanty or lacking in its caudal part and the whole of the
      posterior circulation. A significant finding was that the anterior circulation in
      the majority of individuals is furnished with a varying proportion of SP-IR
      nerves with or without CGRP immunoreactivity. There was a good correlation in the
      expression of CGRP immunoreactivity between SP-IR cells in the ophthalmic
      division of the trigeminal ganglion and SP-IR nerves supplying the major cerebral
      arteries. In the quail, SP- and CGRP-IR fiber bundles are usually present in the
      internal ethmoidal artery (IEA). From these and other findings, it is most
      probable that cerebral perivascular SP- and CGRP-IR nerves are mainly derived
      from the same categories of neurons in the primary sensory ganglion via the IEA.
      The close association of varicose SP-IR axons to the nerve cells in the pial
      arteries suggests that these intrinsic neurons may play some vasocontrolling
      roles through the modulatory effect of their pericellular SP-IR axons.

PMID- 10907684
TI  - An immunohistochemical study of endocrine cells in the alimentary tract of the
      red-bellied frog, Bombina orientalis.
AB  - The regional distribution and relative frequency of endocrine cells was studied
      immunohistochemically (PAP method) in the alimentary tract of the red-bellied
      frog, Bombina orientalis, using antisera against serotonin, somatostatin,
      chromogranin (CG), cholecystokinin (CCK)-8, bombesin, secretin, glucagon and
      pancreatic polypeptide (PP). Eight kinds of endocrine cells were identified in
      this study. These immunoreactive cells were located in the gastric glands of the
      stomach regions and in the intestinal or esophageal epithelium with variable
      frequencies. They were spherical or spindle-shaped. Serotonin- and somatostatin
      immunoreactive cells were demonstrated in the whole alimentary tract including
      esophagus. CG-immunoreactive cells were restricted to the stomach. CCK-8
      immunoreactive cells were observed from the antrum to the ileum. Bombesin
      immunoreactive cells were restricted to the stomach. Secretin-immunoreactive
      cells were demonstrated in the pylorus, duodenum and ileum. Glucagon
      immunoreactive cells were found in the antrum and duodenum. PP-immunoreactive
      cells were detected from the antrum to the rectum. In conclusion, throughout the
      alimentary tract of the red-bellied frog, the different regional distribution and
      relative frequency of endocrine cells were demonstrated. The regional
      distributions and relative frequencies of the endocrine cells in the alimentary
      tract of the red-bellied frog were resembled to those of the other anuran species
      except for esophagus.

PMID- 10907686
TI  - Intrauterine and intravaginal insemination with frozen canine semen using an
      extender consisting of orvus ES paste-supplemented egg yolk tris-fructose
      citrate.
AB  - Our previous report indicated that addition of Orvus ES Paste (OEP) to the
      extender of frozen canine semen protected acrosomes and maintained sperm motility
      after thawing. In this study, artificial insemination (AI) using the frozen semen
      was carried out. The frozen semen was prepared using egg yolk Tris-fructose
      citrate, and the final concentrations of glycerol and OEP were 7% (v/v) and 0.75%
      (v/v), respectively. AI was performed during the optimal mating period predicted
      from the peripheral plasma progesterone level. In intrauterine insemination
      (IUI), the bitches were laparotomized and 1 x 10(8) spermatozoa were infused into
      one of the uterine horns. In insemination of non-OEP supplemented semen, 3 x
      10(8) spermatozoa were inseminated. In intravaginal insemination (IVI), 10-40 x
      10(8) spermatozoa were inseminated. Conception was obtained in nine of 10 bitches
      (90.0%) that underwent IUI. The number of newborns was from 1 to 7 (mean 3.6 +/-
      0.9). The mean ratio of the number of puppies to the number of ovulations in the
      inseminated uterine horn was 71.8%. The number of puppies did not exceed the
      number of ovulation in the inseminated uterine horn. Conception using non-OEP
      supplemented frozen semen was unsuccessful in all four bitches. In IVI,
      conception was not obtained in any of the six bitches that received insemination
      of 10 x 10(8) or 40 x 10(8) spermatozoa, but two of three bitches that received
      insemination of 20 x 10(8) spermatozoa were fertilized. It was shown that a high
      conception rate can be obtained by IUI using OEP-supplemented frozen canine
      semen. Developmenmt of a non-surgical method of IUI and a method of freezing
      canine sperm applicable to IVI is necessary.

PMID- 10907687
TI  - Thyroid hyperactivity induced by methimazole, spironolactone and phenobarbital in
      marmosets (Callithrix jacchus): histopathology, plasma thyroid hormone levels and
      hepatic T4 metabolism.
AB  - To determine drug-induced hyperfunction of marmoset thyroids due to inhibition of
      synthesis or enhancement of metabolic elimination of thyroid hormones, males were
      orally administered 10 and 30 mg/kg/day methimazole (MMI), 30 and 100 mg/kg/day
      spironolactone (SPL), or 50 mg/kg/day phenobarbital (PB) for 4 weeks. MMI caused
      marked hypertrophy of follicular epithelial cells in accordance with a
      significant decrease in the plasma thyroxin (T4) level. Hypertrophied epithelial
      cells were filled with dilated rough endoplasmic reticulum and reabsorbed
      intracellular colloids, and the luminal surface was covered with abundant
      microvilli. The colloid included vacuoles positive to anti T4 immuno-staining.
      SPL and PB also caused similar histomorphological changes, although they were
      less severe than those due to MMI and were not clearly associated with decrease
      in the plasma T4 levels. Hepatic T4 UDPGT activities tended to increase due to
      SPL and PB treatment, however, which were not so significant as increases in
      microsomal cytochrome P-450 contents. Some animals treated with SPL and PB showed
      marked increases in thyroid weights due to inactive dilated follicles. In
      conclusion, hyperactivity of thyroid follicles was induced in marmosets not only
      due to inhibition of T4 synthesis produced by MMI but also because of enhancement
      of hepatic T4 elimination produced by SPL and PB. However, hypertrophic effects
      of SPL and PB were less severe than MMI, because plasma T4 levels were maintained
      at almost pretreatment or control levels after SPL or PB treatment.

PMID- 10907688
TI  - Detection of Salmonella by using the colorimetric DNA/rRNA sandwich hybridization
      in microtiter wells.
AB  - A rapid and readily available DNA probe kit was developed for the detection of
      Salmonella spp. This kit utilized the colorimetric DNA/rRNA sandwich
      hybridization method in microtiter wells. Within 3 hr Salmonella spp. in
      selective enrichment broth cultures were detected by the DNA probe kit. The kit
      effectively identified all of 187 strains of Salmonella tested and yielded no
      false-positive reactions in the examination of 674 pure cultures of non
      salmonellae. The DNA probe kit could detect 10(5) cfu/ml in pure culture. A total
      of 379 naturally contaminated samples (raw chicken meat, liquid egg, animal
      feeds, poultry feces and frozen foods) were tested, both by the standard culture
      method and the DNA probe kit. The 169 of these samples were culture positive and
      210 were culture negative. The sensitivity of the DNA probe kit was 98.2%
      (166/169) and the specificity was 99.5% (209/210). These results show that the
      DNA probe kit is a useful tool to examine a large number of various samples for
      contamination by Salmonella spp. in food and livestock industry.

PMID- 10907689
TI  - Involvement of apoptosis in the endotoxemic lesions of the liver and kidneys of
      piglets.
AB  - The involvement of apoptosis was evaluated in lesions of endotoxemic piglets. A
      single injection with E. coli O111:B4 lipopolysaccharide (LPS) induced foci of
      coagulative necrosis in the liver and kidneys. No significant change was observed
      in these organs at 1.5 hr after LPS injection, but at 6 hr, epithelial cells with
      chromatin condensation or fragmentation and apoptotic bodies were visible. Foci
      of coagulative necrosis were formed within 24 hr after LPS inoculation. In and
      adjacent to the necrotic foci, dead hepatocytes with nuclear condensation or
      fragmentation were scattered. These dead cells were positively stained by
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling
      (TUNEL) methods. Electronmicroscopy revealed apoptotic cells with condensed or
      fragmented homogeneous nuclear chromatin, and necrotic cells with irregularly
      destroyed nuclei and cytoplasmic membranes. Apoptotic cell death were also
      observed in parietal cells of the stomach and lymphocytes in the lymphatic
      system. DNA ladders with approximately 200-bp multimers were observed in hepatic,
      renal and thymic samples prepared after 6 and 24 hr of LPS injection by agarose
      gel electrophoresis. These results suggest that apoptosis is involved in the
      pathology of swine endotoxemia.

PMID- 10907690
TI  - Evidence of porcine circovirus infection in pigs with wasting disease syndrome
      from 1985 to 1999 in Hokkaido, Japan.
AB  - An epizootiological survey with histopathological methods was conducted for
      porcine circovirus in 220 diseased pigs (1-200 days old) in 49 farms from 1985 to
      1999. Histopathological lesions containing PCV antigen were detected mainly in
      the lymphoid tissues from 42 of 189 diseased pigs (22.2%) in 4 of 45 farms (8.9%)
      from 1990 to 1999. The rate of positive pigs gradually increased from 1997 onward
      and PCV infection was found in 50% of diseased pigs in 1999. Histopathologically,
      the lesions in the lymphoid tissues (including lymph nodes, Peyer's patches,
      tonsil and spleen) were highly correlated with the presence of numerous spherical
      basophilic intracytoplasmic inclusion bodies with PCV antigen, and consisted of
      lymphocellular depletion and infiltration of macrophages. Although most affected
      cells showed cytoplasmic reactivity for PCV, intranuclear antigen was also seen
      in the lymphocytes, macrophages and ileal epithelial cells. Ultrastructurally,
      macrophages and giant cells contained electron-dense, round to ovoid lysosomal
      bodies, in which there were concentric circle or paracrystalline arrays of small
      nonenveloped icosahedral viral particles, approximately 15-17 nm in diameter.
      Other consistent infectious agents were present in 90.5% of cases, and porcine
      reproductive and respiratory syndrome virus infection was in 52.4% of the cases
      with PCV. The histopathological findings suggested that PCV induced systemic
      immunosuppression in the infected pigs and made them more susceptible to
      infection of the organisms. Because of the presence of PCV antigens in the
      intestinal epithelium, feces may play a significant role in dissemination of PCV.

PMID- 10907692
TI  - Listeriosis in a raccoon dog (Nyctereutes procyonoides) associated with canine
      distemper.
AB  - A wild raccoon dog (Nyctereutes procyonoides) that manifested severe illness and
      died was examined. Necropsy revealed severe emaciation, systemic icterus and
      petechial hemorrhages on the mucous membranes. Histopathologically, necroses were
      seen in the liver and brain stem associated with meningitis. Eosinophilic
      intranuclear inclusion bodies were observed in the spleen and intestinal mucosa,
      and eosinophilic intracytoplasmic inclusion bodies were seen in transitional
      epithelium in the bladder. Listeria monocytogenes 4b was isolated from the liver,
      spleen, kidneys and lungs, and the pathogen was also detected in the liver and
      brain stem immunohistopathologically. The disease was diagnosed as listeriosis
      associated with canine distemper virus infection in a raccoon dog.

PMID- 10907691
TI  - Seroprevalence of Bartonella henselae and Toxoplasma gondii among healthy
      individuals in Thailand.
AB  - The seroprevalence of Bartonella henselae and Toxoplasma gondii among apparently
      healthy individuals, mainly blood donors, in Thailand was investigated by an
      indirect fluorescent antibody technique and by a latex agglutination test,
      respectively. Of 163 serum samples examined, 9 (5.5%) were found to be positive
      for B. henselae-IgG, 2 (1.2%) for B. henselae-IgM, and 5 (3.1%) for the T. gondii
      antibody. No significant difference was observed between male and female samples
      in the serological test with either B. henselae or T. gondii. The age of
      individuals with B. henselae-IgG was distributed from the 20s to the 70s, and B.
      henselae-IgM was found in the individuals of the 30s and 60s. The age of T.
      gondii positive samples ranged from the 20s to the 60s. In this study, the
      prevalence of B. henselae infection among healthy individuals in Thailand was
      serologically demonstrated for the first time.

PMID- 10907693
TI  - In vitro detection of equine arteritis virus from seminal plasma for
      identification of carrier stallions.
AB  - Equine arteritis virus (EAV) was readily isolated in RK-13 cell monolayers by
      plaque assay from seminal plasma of experimental carrier stallions when they
      contained high titers of virus regardless of the presence of non-viral
      cytotoxicity in the seminal plasma. The cytotoxicity interfered with virus
      isolation from seminal plasma which contained virus at titers less than 10
      PFU/ml. However, it was possible to detect the virus in seminal plasma pretreated
      with PEG (#6000). EAV was consistently identified by RT-PCR from crude seminal
      plasma which contained virus at titers of more than 10(2.7) PFU/ml. In vitro
      detection of EAV by virus isolation supplemented with RT-PCR using seminal plasma
      was proved to be an effective alternative to the standard test mating as a
      diagnostic method for carrier stallions.

PMID- 10907694
TI  - Relationship between the responsiveness to multiple-ovulation treatment and the
      number of bovine oocytes collected by transvaginal follicle aspiration.
AB  - To characterize factors affecting the number of bovine oocytes recovered
      transvaginally, a regression analysis was performed between the responsiveness to
      multiple-ovulation treatment and the number of oocytes recovered transvaginally.
      The number of embryos recovered following multiple-ovulation treatment and the
      number of oocytes recovered transvaginally increased when the number of follicles
      to be aspirated transvaginally increased (P<0.05. P<0.01). The number of cumulus
      oocyte complexes recovered transvaginally also increased when the number of
      oocytes to be aspirated transvaginally increased (P<0.001). However, the number
      of viable embryos that recovered following multiple-ovulation treatment had no
      relation to the number of cumulus-oocyte complexes recovered transvaginally.
      These results suggested that more oocytes can be recovered from donors that have
      a high responsiveness to multiple-ovulation treatment.

PMID- 10907695
TI  - Double-chambered right ventricle in a dog.
AB  - A 32-month-old spayed female Pug was referred for an MRI study due to
      convulsions. The MRI examination indicated encephalitis. However,
      echocardiography and pathological examinations revealed that this case had a
      ventricular septal defect and double chambered right ventricle which is a rare
      congenital heart disease in the dog. An anomalous muscle bundle crossed the right
      ventricular outflow tract, dividing the right ventricle into 2 chambers.

PMID- 10907696
TI  - Amyloid-producing odontogenic tumor in a Shih-Tzu dog.
AB  - A 9-month-old male Shih-Tzu dog had a right mandibular tumor composed of strands,
      or nest-like proliferation of epithelial cells with abundant fibrous stroma
      characterized by spheroid to large nodular deposition of amyloid with Congo-red
      stain. Globule calcification was also seen throughout the tumor tissue and the
      spheroid depositions often had a concentrically laminated structure (Liesegang
      rings). The case was diagnosed as amyloid-producing odontogenic tumor in a dog.

PMID- 10907697
TI  - The susceptibility of culture cells to avian influenza viruses.
AB  - The susceptibilities of culture cells to twelve avian influenza virus strains
      were determined with ten established cell lines including MDCK and ESK cells and
      three primary culture cells. The established cell lines derived from embryonic
      swine kidney (ESK) and chicken kidney (CK) primary culture cells were more
      sensitive to the avian influenza viruses than the other eleven cells. The ESK
      cell had a particularly higher infective titer than the MDCK cell with and
      without trypsin supplement in culture medium, and dispersion of the infective
      titers was narrower than that of the MDCK cell. The ESK cell is a suitable
      candidate for routine work on avian influenza viruses in laboratories.

PMID- 10907698
TI  - ELISA for bovine interleukin-1 receptor antagonist and its application to
      mastitic sera and whey.
AB  - A sandwich ELISA for the bovine IL-1 receptor antagonist (bIL-1ra) was developed
      using recombinant (r) bIL-1ra produced by Escherichia coli, anti-rbIL-1ra rabbit
      IgG, its biotinylated one and avidin-peroxidase. This ELISA system enabled
      detection of rbIL-1ra at a concentration of more than 2 ng/ml. This ELISA was
      applied to quantitation of bIL-1ra in sera and whey of mastitic and healthy cows.
      The results indicate that although IL-1ra levels in healthy and mastitic sera and
      whey were comparable, serum IL-1ra/IL-1beta ratio of euthanized cows was
      significantly lower than that of the recovered.

PMID- 10907699
TI  - Effects of perineural capsaicin treatment on cardiopulmonary reflexes elicited by
      laryngeal instillations of capsaicin and distilled water in sevoflurane
      anesthetized dogs.
AB  - The aim of this study was to determine the effect of perineural capsaicin (CAPS)
      treatment on cardiopulmonary reflexes elicited by topical laryngeal instillation
      of CAPS and distilled water (DW) in sevoflurane-anesthetized dogs.
      Cardiopulmonary reflexes elicited by CAPS (10 microg/ml, 10 ml) were attenuated
      by perineural CAPS treatment to the superior laryngeal nerves (SLNs) (P<0.05),
      whereas those by DW (10 ml) remained unaffected (P>0.05). The reflex responses to
      DW that remained even after the perineural CAPS treatment were eliminated by
      laryngeal anesthesia with lidocaine. These results suggest that cardiopulmonary
      reflexes from the laryngeal mucosa elicited by CAPS instillation can be blocked
      by perineural CAPS treatment to the SLNs, which may result from inhibition of the
      laryngeal CAPS-sensitive C-fiber afferents.

PMID- 10907701
TI  - Incidence of Listeria monocytogenes in wild animals in Japan.
AB  - Between 1991 and 1993, the intestinal contents and feces of wild animals in Japan
      were examined for the presence of Listeria. The wild animals examined included
      623 mammals (11 species) and 996 birds (18 species). Listeria species were
      isolated from 38 (6.1%) of the 623 mammalian samples and 133 (13.4%) of 996 bird
      samples. The highest incidence of Listeria in the mammals was found in Japanese
      monkeys (20.0%) and that in birds was found in crows (43.2%). The incidence of
      Listeria in Japanese monkeys varied from 0 to 40.0% depending on the capture
      area. L. monocytogenes was isolated from II of these positive samples. Serovars
      1/2a and 4b predominated in eight serotyped L. monocytogenes isolates.

PMID- 10907700
TI  - Sex determination based on fecal DNA analysis of the amelogenin gene in sika deer
      (Cervus nippon).
AB  - A sex determination method using DNA extracted from feces has been developed for
      sika deer (Cervus nippon). We determined a partial sequence of the amelogenin
      gene of sika deer, which exists on both X and Y chromosomes with a deletion
      region on the Y chromosome. Based on the sexually dimorphic sequences, we
      designed a pair of primers which could amplify DNA fragments the lengths of which
      are different between males and females. PCR products were detected in 34 out of
      37 fecal samples collected from captured deer and the sexes estimated by the
      present method were perfectly matched with the actual sexes.

PMID- 10907702
TI  - Taking breaks from work: an exploratory inquiry.
AB  - Two studies concerned with taking breaks from either mental or physical work are
      presented. In the first study, a questionnaire was given to 101 students in which
      they answered questions about their own break taking and that of others. They
      also completed a time management questionnaire and scales about procrastination,
      self-esteem, and work overload. In the second study, 17 students kept detailed
      diaries of their daily break-taking behavior over a 6-week period. Results are
      discussed in terms of the types of reasons given for taking breaks and the
      possible discrepancies between such reasons and the actual activities engaged in
      during breaks.

PMID- 10907703
TI  - Substantive differences in the assertiveness of low-income African American,
      Hispanic, and Caucasian women.
AB  - A sample of 115 low-income African American, Hispanic, and Caucasian women
      participated in 6 assertiveness role plays. A content analysis of their responses
      indicated that there are substantive differences in terms of what constitutes
      passive, assertive, and aggressive responses. The findings suggest that there are
      basic conceptual differences across the groups regarding connections and
      obligations to others. Differences in perceptions of assertiveness point to the
      culturally specific nature of assertiveness. Functionally, each group of women
      was able to stand up for themselves, yet boundaries between appropriate and
      inappropriate responding were placed somewhat differently across groups,
      depending on the situation.

PMID- 10907704
TI  - Influence of role and gender on the use of distributive versus procedural justice
      principles.
AB  - Differences in perceptions of fairness may result from differential emphasis on
      distributive and procedural justice. The author found that organizational role
      and gender influenced the extent to which distributive and procedural justice
      principles were used when participants allocated and evaluated pay raises. When
      participants took the role of a supervisor, they were more likely to use
      procedural justice principles; when they took the role of a subordinate, they
      were more likely to use distributive justice principles. Also, men were more
      likely to use distributive justice than procedural justice principles when
      allocating and evaluating raises. These findings suggest that organizations
      should become aware of individual and role-based differences in emphasis on
      justice-related factors that could potentially lead to perceptions of unfairness.

PMID- 10907705
TI  - Behavioral and cognitive correlates of exercise self-schemata.
AB  - The purpose of this study was to examine the relationship of exercise self
      schemata to both cognitive and behavioral concomitants including exercise self
      efficacy, attitudes toward fitness, self-perceptions of fitness, and self-report
      of exercise behavior. Participants were 161 undergraduate students who
      subsequently were categorized into groups defined by the authors as "exercise
      schematics," "nonexercise schematics," "aschematics," and unclassified. Results
      indicated that exercise schematics reported greater total caloric expenditure,
      higher frequency of exercise behavior in the past as well as future expectations
      to exercise, greater self-perceptions of physical fitness, and more favorable
      attitudes toward fitness than either nonexercise schematics or aschematics.
      Furthermore, exercise schematics expressed higher levels of exercise self
      efficacy than did nonexercise schematics. The results clearly support earlier
      findings concerning exercise self-schemata and exercise behavior and further
      indicate that schematics also differ from others in important cognitive
      motivational determinants of exercise such as self-efficacy and perceptions of
      physical fitness. Future research should define the role of exercise self
      schemata both theoretically and practically in order to enrich our understanding
      of and facilitate the enhancement of exercise adherence.

PMID- 10907706
TI  - Terminal illness and coping with loneliness.
AB  - Loneliness is a universal phenomenon, and its pain is intensified by a diagnosis
      of a terminal illness. The present study is an investigation of the coping
      strategies used by HIV/AIDS patients, by individuals diagnosed with cancer, and
      by the general population. Forty-three HIV/AIDS patients, 38 cancer patients, and
      53 participants from the general population answered a 34-item questionnaire.
      Results indicated that with the exception of reflection and acceptance and
      religion and faith, those afflicted with HIV/AIDS cope with loneliness
      significantly differently from members of the other two groups. The findings of
      this exploratory study suggest that cancer patients and the general population do
      not differ in the ways they cope with loneliness.

PMID- 10907707
TI  - Change in value orientations of Turkish youth from 1989 to 1995.
AB  - The purpose of this study was to investigate the changes in value orientations of
      Turkish youth from 1989 to 1995 and to see how changes in Turkish society
      affected the value orientations of Turkish youth. The Rokeach Value Survey (RVS;
      M. Rokeach, 1973) was administered in Ankara to 289 young people in 1989, to 318
      young people in 1992, and to 397 young people in 1995. Results indicated that the
      value orientations of the Turkish youth in 1989 underwent major changes that were
      manifested in 1992, toward a more competitive and individualistic orientation.
      Similar characteristics were reflected in the value priorities of the young
      people in 1995, which indicates that values are modified to fit the changes the
      society experiences.

PMID- 10907708
TI  - Future time orientation and relationships with the opposite sex.
AB  - This study is an examination of future time orientation (FTO) and relationship
      satisfaction. Undergraduate students (N = 244) from Middle East Technical
      University were given a general FTO scale developed by T. Gjesme (1979) and a
      scale developed by this study's researcher to measure FTO in terms of romantic
      relationships. Participants were asked to rate their relationship satisfaction on
      a 9-point Likert-type scale. Although a general FTO was adaptive in terms of
      romantic relationships, a high concern for future commitment to a romantic
      relationship had a negative effect on reported relationship satisfaction.
      Research implications and suggestions for future studies are discussed.

PMID- 10907709
TI  - Religiosity and agency and communion: their relationship to religious
      judgmentalism.
AB  - The present study is an introduction to the construct of religious judgmentalism,
      defined as a willingness to make religious or moral judgments of others based on
      a limited period of observation; the study offers a prediction about which
      individuals will engage in such judgmental behavior. It was predicted that agency
      motives would significantly predict religious judgmentalism in a religious
      population but that communion motives and intrinsic religiosity would moderate
      this effect. Overall, the findings supported these predictions. Agency motives
      were positively correlated with religious judgmentalism. Intrinsic religiosity
      predicted a general unwillingness to make religious evaluations of others. Both
      intrinsic religiosity and communion motives did moderate the effects of high
      agency motives. Specifically, increases in communion motive and intrinsic
      religiosity, at high levels of agency motives, significantly predicted lower
      scores for religious judgmentalism. These findings were conceptualized as
      preliminary evidence for the position that interpersonal motives, rather than
      religiousness or religious motivation, predict social intolerance and criticism
      in religious individuals.

PMID- 10907710
TI  - The equivalence of contingency structure for intuitive covariation judgments
      about height, weight, and body fat.
AB  - In a complete between-subjects design, 576 respondents judged covariations of
      problems framed around height, weight, and body fat. A verbal measure was used,
      consisting of propositional statements representing relationships between two of
      the variables, as well as two types of response options: true or false, and a 7
      point, bipolar, Likert-type scale. Consistent with previous findings, weight and
      body fat were unambiguously judged as if positively correlated; there were
      indications of a perceived negative correlation of height and body fat; and there
      was no evidence that participants regarded height and weight as positively
      correlated. Furthermore, there was no reliable evidence in support of framing
      effects. However, there were indications of influence for conditional format.
      These findings are discussed relative to previous and ongoing research efforts,
      and it is concluded that it may be inappropriate to regard variations in
      conditional format as parallel items. Measures involving all possible variations
      are considered fundamentally unbiased and consistent with I. Ajzen's (1988)
      principle of aggregation.

PMID- 10907711
TI  - Relationship satisfaction and conflict style in romantic relationships.
AB  - The aim of this study was to determine to what extent the association between
      relationship satisfaction and a negative conflict style in romantic relationships
      may be due to the frequency of conflict or of conflict not satisfactorily
      resolved. The 6-item Relationship Assessment Scale (S. S. Hendrick, 1988) and an
      11-item conflict scale created by the author for this study were completed by a
      group of young British adults (65 women and 30 men) concerning their current
      romantic relationships, all of which were heterosexual. The results confirmed
      that a negative conflict style was significantly associated with relationship
      satisfaction when either conflict or conflict not satisfactorily resolved was
      controlled. Conflict not satisfactorily resolved was also significantly
      correlated with relationship satisfaction when either conflict or a negative
      conflict style was controlled. Conflict and a negative conflict style were also
      significantly correlated with relationship duration.

PMID- 10907712
TI  - The effect of perceived duration of physical disability on attitudes of school
      children toward friendship and helping.

PMID- 10907713
TI  - Experiences of longing in six-year-old Swedish children.

PMID- 10907714
TI  - The factor structure and reliability of a scale measuring the manifest and latent
      dimensions of employment.

PMID- 10907715
TI  - Communication disorders in the 22Q11.2 microdeletion syndrome.
AB  - The 22q11.2 microdeletion syndrome is a genetic disorder that is being recognized
      with increasing frequency. Confirmation of the diagnosis can be made using
      fluorescence in situ hybridization. Many medical and developmental problems are
      present in children with this syndrome. Communication disorders are among the
      most common features of this syndrome and include articulation, language,
      resonance, and voice problems. The purpose of this paper is to provide a
      description of the communicative and developmental features in a sample of
      children with the 22q11.2 microdeletion syndrome seen for evaluation. Because
      communication and feeding disorders may be presenting features of this syndrome,
      speech and language pathologists must be familiar with this syndrome and its
      various characteristics. Awareness of these features and a multidisciplinary
      approach are necessary for the identification and treatment of the complex
      communicative and medical problems present in this population.

PMID- 10907716
TI  - Partnership in conversation: a study of word search strategies.
AB  - Conversation analysis was used to investigate a conversational partner's
      strategies when assisting with the word searches of an aphasic person. The
      purpose was to identify and detail how such strategies were accomplished and to
      examine the implications of these strategies from a social and participatory
      perspective. Review of a large, authentic database resulted in identification of
      38 videotaped conversation sequences characterized by the initiation of a word
      search by an aphasic speaker and the joining of this search by the conversation
      partner. Sequences were analyzed on a turn-by-turn basis to identify patterns of
      sequential organization based on similarities in contextual and functional
      features and to infer social implications. Results were that four conversation
      strategies were systematically used: guess, alternative guess, completion, and
      closing strategies. Each was accomplished collaboratively with specific
      interactional resources and techniques and were used differentially for social
      purposes. Implications for clinical practices involving training of conversation
      partners are discussed.

PMID- 10907717
TI  - Dysfluency and phonic tics in Tourette syndrome: a case report.
AB  - Tourette syndrome, a condition first recognized in 1825, is characterized by the
      presence of multiple motor tics and one or more phonic tics. Individuals with
      Tourette syndrome may also demonstrate fluency failures in their speech. This
      study investigated the disfluencies and phonic tics in an 18-year-old affected
      male before and after a three week period of speech therapy. It was found that
      the speech pattern displayed by this subject did not completely conform to the
      classic pattern of stuttering but did bear more resemblance to cluttering. A
      limited number of therapy sessions resulted in a significant improvement of
      speech.

PMID- 10907718
TI  - Novel word acquisition in children with Down syndrome: does modality make a
      difference?
AB  - Signing is a commonly used intervention technique for children with cognitive
      impairments who have expressive language delays. Novel word learning in three
      conditions (signed only, spoken only, signed and spoken combined) was compared
      for children with Down syndrome (2;1 to 5;2) and mental-age matched control
      children (1;4 to 2;6). Spontaneous imitations and responses to production and
      comprehension probes were examined after 5, 10, and 15 word exposures. No group
      differences in frequency of imitations or productions were obtained. The
      frequency of imitations was highest in the combined condition. Probed productions
      were infrequent, although novel words were produced most often in spoken and
      combined conditions. For both imitated and probed productions in the combined
      condition, the spoken portion was almost exclusively produced. Across conditions,
      children with Down syndrome comprehended fewer words than did control children.
      The evidence for and explanations of the facilitative effect of signs and the
      advantage of dual-method presentation are discussed.

PMID- 10907719
TI  - Evaluation of in vivo binding properties of 3H-NMPB and 3H-QNB in mouse brain.
AB  - Apparent muscarinic acetylcholine (mAch) receptor occupancy in mouse cerebral
      cortex, hippocampus, and striatum by scopolamine, an antagonist, and biperiden, a
      relatively selective M1 antagonist, was estimated with competitive binding
      studies using two different radioligands: 3H-N-methyl piperidyl benzilate (3H
      NMPB) and 3H-quinuclidinyl benzilate (3H-QNB). Both radioligands labeled mAch
      receptors in these brain regions, and the relative regional distributions of the
      specific binding of 3H-NMPB in vivo paralleled the distribution of mAch
      receptors. 3H-NMPB binding in vivo was much more sensitive to direct competitive
      inhibition by scopolamine than was 3H-QNB. A similar discrepancy in sensitivity
      to competitors between 3H-NMPB and 3H-QNB was also observed when biperiden was
      used as a competitor, indicating that binding to different subtypes of the mAch
      receptor could not account for the observed differences in sensitivity to
      competition. An in vivo saturation study suggested that the apparent association
      rate constant (k on) of 3H-QNB binding might be changed by ligand concentration.
      The heterogeneity of the free ligand concentration in intact brain was assessed
      in relation to the ligand concentration dependency of the apparent association
      rate constant (k on) of 3H-QNB binding. This finding, together with the more
      favorable accumulation of 3H-NMPB in cerebral cortex, hippocampus, and striatum,
      leads us to conclude that 3H-NMPB, or its positron emitting counterpart, should
      be the more favorable radiotracer for the estimation of mAch receptor occupancy
      by cholinergic drugs in the brain. KEYWORDS: mAch receptor, QNB, NMPB, in vivo,
      mouse.

PMID- 10907720
TI  - Studies with rasagiline, a MAO-B inhibitor, in experimental focal ischemia in the
      rat.
AB  - Rasagiline, as the mesylate salt (TVP-1012), is a selective, potent, non
      reversible MAO-B inhibitor of the propargylamine type. Current cellular and whole
      animal studies suggested a potential for neuroprotection by rasagiline.
      Rasagiline in repeat ip doses of 1-3mg/kg within 16h, or by sustained iv infusion
      to maintain a 3-h steady-state at corresponding levels, improved the outcome of
      permanent middle cerebral artery occlusion (MCAO) in the rat. In five independent
      studies using different protocols, rasagiline improved neurological severity
      score (NSS) with respect to saline from a high of 8.96 +/- 2.18 (n = 94) at 24h,
      and 7.64 +/- 2.52 (n +/- 49) at 48h, to a low of 7.13 +/- 2.32 (n = 88) at 24h,
      and 4.99 +/- 2.31 (n = 68) at 48h. Under the same conditions, there was a
      decrease in the volume of necrotic brain region determined at 48h by triphenyl
      tetrazolium chloride (TTC), from a high of 240 +/- 66 (n = 54) to a low of 176 +/
      77 mm(3) (n = 55); and by MRI scan at 48h, from a high of 297 +/- 62 (n = 25),
      to a low of 209 +/- 63 mm(3) (n = 28). Improvement in NSS was more obvious at 48h
      post MCAO, at the higher dose, when timing of drug administration was within the
      interval -30 min to 3 h from MCAO. A 3-h iv infusion of rasagiline caused a
      maximal reduction in infarct volume of about 49% of control. The (S)enantiomer of
      rasagiline TVP-1022, not a MAO inhibitor, was less effective, but still
      significantly different from saline, NSS at 48h 5.6 +/- 2.5 (n = 24) vs. 7.5 +/-
      2.5 (n = 24), infarct volume 200 +/- 64 (n = 24) vs. 240 +/- 55 mm(3) (n = 24).
      Selegiline (n = 19) at corresponding ip doses was not different from saline.
      Dizocilpine decreased infarct volume from 277 +/- 65 (n = 20) to 203 +/- 52mm(3)
      (n = 21) but could not improve NSS at 24 or 48h. In this model, rasagiline could
      have exerted a neuroprotective effect independent of MAO inhibition.

PMID- 10907721
TI  - Specific localization of the guanosine triphosphate (GTP) cyclohydrolase I
      immunoreactivity in the human brain.
AB  - Guanosine triphosphate (GTP) cyclohydrolase I (GCH) is the first and rate
      limiting enzyme for biosynthesis of tetrahydrobiopterin, the cofactor of tyrosine
      hydroxylase (TH). Our previous study reported the presence of GCH in several
      neuronal groups in animal brains using a newly raised anti-GCH antibody. The
      present study aims at elucidating whether GCH and TH coexist in the same neurons
      of the human brain with the aid of immunohistochemical dual labeling. GCH
      immunoreactivity was observed in the cell bodies and fibers of monoaminergic
      neurons of the human brain. Neurons which contain both enzymes are seen in the
      human substantia nigra, ventral tegmental area, locus coeruleus, dorsal raphe,
      and zona incerta. In these regions, almost all the cells also show
      immunoreactivity for aromatic L-amino acid decarboxylase (AADC), the second step
      enzyme for catecholamine synthesis, indicating that these neurons are
      catecholaminergic. However, some neurons in the dorsal and dorsomedial
      hypothalamic nuclei are stained only for GCH or TH. They appear to constitute an
      independent cell group in the human brain. The present observation suggests that
      L-dopa is not produced in the cells immunoreactive for TH but not for GCH, and
      that TH in these cells which lack GCH may have an unidentified role other than
      dopa synthesis.

PMID- 10907722
TI  - Dose-dependent effects of noradrenergic denervation by DSP-4 treatment on forced
      swimming and beta-adrenoceptor binding in the rat.
AB  - DSP-4 is a neurotoxin highly selective for the noradrenergic nerve terminals
      originating from the locus coeruleus. Preliminary data suggested that its effect
      in a typical screening test for antidepressant drugs, the forced swimming test,
      is biphasic dependent on the dose. In the present study, DSP-4 was administered
      in four doses (5, 10, 30 and 50mg/kg) to male Wistar rats. Administration of the
      neurotoxin had a dose-dependent biphasic effect on immobility time in the forced
      swimming test 8 and 9 days later. Thus, DSP-4 at the dose of 10mg/kg increased
      immobility, but higher doses reduced this measure. The reduction of noradrenaline
      concentration in the frontal cortex and hippocampus was dose-dependent starting
      from the dose 10mg/kg. Cortical beta-adrenoceptor binding was increased by DSP-4
      treatment at the doses 30mg/kg and 50mg/kg. These results suggest that the
      increase in immobility time in the forced swimming test is associated with
      presynaptic changes in noradrenaline availability, whereas the decrease in
      immobility observed after more complete denervation is associated with
      postsynaptic receptor supersensitivity.

PMID- 10907723
TI  - Facilitation of sympathetic neurotransmission contributes to angiotensin
      regulation of body weight.
AB  - Previous studies demonstrated that angiotensin II (AnglI) decreases body weight.
      The purpose of this study was to determine if AngII-reductions in body weight
      result from stimulation of sympathetic neurotransmission to interscapular brown
      adipose tissue (ISBAT). Following 7 days of chronic AngII infusion
      (350ng/kg/min), body weight decreased compared to controls. Using superfused
      ISBAT tissue slices preloaded with [3H]norepinephrine (NE), evoked [3H]overflow
      was greater in ISBAT slices from AngII-infused rats compared to controls. When
      AngII was included in the buffer, evoked [3H]overflow increased in a
      concentration-dependent manner in ISBAT slices from AngII-infused and control
      rats. The EC50 for the presynaptic effect of AngII was shifted to the left in
      ISBAT slices from AnglI-infused rats compared to controls; however, the maximal
      response to AngII was decreased. These results demonstrate that chronic AngII
      infusion enhances evoked release of NE from ISBAT sympathetic nerve terminals.
      Moreover, responsiveness to the presynaptic effect of AngII was altered following
      chronic AngII infusion. Increased sympathetic neurotransmission to ISBAT may
      contribute to AnglI-regulation of body weight.

PMID- 10907724
TI  - Supersensitivity with reduced capacity for pineal melatonin synthesis in constant
      light-treated rats.
AB  - Melatonin is synthetized from serotonin in two steps driven by the enzymes N
      acetyltransferase and hydroxyindole-O-methyltransferase. Constant light treatment
      reduces rat pineal hydroxyindole-O-methyltransferase activity while the
      activation of N-acetyltransferase becomes supersensitive to adrenergic
      stimulation. We studied the effect of this discrepancy on the production of
      melatonin. Male rats were kept under 12/ 12-h light/dark (LD) conditions or for 7
      days under constant light (LL). They received subcutaneous injections of
      isoproterenol or methoxamine in the middle of the light period (LD-rats) or the
      estimated rest phase (LL-rats). A low dose of isoproterenol (0.1 mg/kg) increased
      pineal melatonin only marginally in LD-rats, while a maximum effect was found in
      LL-rats. A medium dose (0.2mg/kg) produced similar levels in both groups. A high
      dose (0.4 mg/kg) elevated pineal melatonin contents significantly more in normal
      than light-treated rats. Methoxamine (0.8 mg/kg) had no effects alone nor
      combined with isoproterenol. The results suggest supersensitivity with reduced
      capacity for melatonin formation in constant light-treated rats.

PMID- 10907725
TI  - Molecular cloning and functional expression of the mouse dopamine transporter.
AB  - The full coding region of the murine dopamine transporter (mDAT) cDNA was cloned
      by PCR with a sense primer derived from the partial mDAT gene sequence and an
      antisense primer deduced from the rat dopamine transporter cDNA. The mDAT cDNA
      encodes a typical member of the family of Na+- and Cl--dependent neurotransmitter
      transporters with 99.2; 93.4 and 85.4% amino acid identity to the rat, human and
      bovine DATs, respectively. Functional expression of the mDAT cDNA in transiently
      transfected human embryonic kidney (HEK293) cells exhibited the typical
      pharmacological features of a dopamine transporter. [3H]dopamine uptake through
      the mDAT was inhibited with high potency by GBR12909 (IC50 = 5.2 nM) and not
      significantly affected by 100 nM desipramine. [3H]dopamine uptake also was
      inhibited through increasing concentrations of dopamine (IC50 = 0.93 microM) or 1
      methyl-4-phenylpyridinium (MPP+; IC50 = 13.2microM).

PMID- 10907727
TI  - Reduced platelet glutamate uptake in Parkinson's disease.
AB  - Defects in mitochondrial enzymes have been found not only in substantia nigra,
      but also in platelets from Parkinson's Disease (PD) patients, suggesting a
      systemic impairment of energy metabolism. Since platelets present an energy
      dependent glutamate uptake similar to that described in central nervous system,
      glutamate uptake was determined in platelets from 34PD patients and 21 age
      related normal controls, as Na+-dependent [3H]glutamate influx; glutamate level
      was also analyzed by reverse-phase HPLC. A 50% reduction of glutamate uptake (p <
      0.001) was observed in idiopathic PD patients, respect to controls and secondary
      parkinsonian syndromes. The decrease correlated with the severity of PD, measured
      by the UPDRS (r = -0.54; P < 0.05). Glutamate level was increased in platelets of
      PD patients, but was not correlated to the uptake decrease. Both phoenomena may
      be explained by the modifications of mitochondrial enzymes described in
      platelets, which could be used as a peripheral model of glutamatergic function in
      PD.

PMID- 10907726
TI  - Chronic supranigral infusion of BDNF in normal and MPTP-treated common marmosets.
AB  - BDNF or vehicle were administered by unilateral supranigral infusion in normal
      and chronically lesioned MPTP-treated common marmosets (Callithrix jacchus) for
      four weeks and locomotor activity, disability and response to apomorphine were
      assessed with nigral TH, GFAP and GAD immunoreactivity and striatal [3H]mazindol
      autoradiography. Selective contraversive orientation and ipsilateral neglect
      evolved in MPTP-treated marmosets receiving BDNF with no significant difference
      in disability or locomotor activity when compared to the vehicle-infused group.
      Apomorphine produced an ipsiversive rotational bias in BDNF-treated animals. In
      normal animals infused with BDNF contralateral neglect, ipsiversive turning,
      postural instability and ataxia rapidly evolved. In MPTP-treated marmosets BDNF
      caused increased ipsilateral striatal [3H]mazindol binding with increased somatic
      size and staining intensity in GAD-immunoreactive cells and a 10-20% loss of
      nigral TH-immunoreactive cells with increased GFAP staining. In normal common
      marmosets, both vehicle and BDNF infusion decreased nigral TH-immunoreactivity.
      Chronic supranigral infusion of BDNF alters motor behaviour and spatial attention
      in MPTP-treated marmosets which may reflect altered function in residual nigral
      dopaminergic neurons and brainstem GABAergic neurons and in normal animals
      produces behavioural and histological signs of nigrostriatal hypofunction.

PMID- 10907728
TI  - Deep brain stimulation of the subthalamic nucleus for control of extrapyramidal
      features in advanced idiopathic parkinson's disease: one year follow-up.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) with a quadripolar
      electrode was carried out in 9 patients with advanced idiopathic Parkinson's
      disease (PD) affected with severe diurnal motor fluctuations. The effect of
      bilateral STN stimulation was evaluated by clinical methods in all patients after
      3 and 12 months. Assessment was based on the Unified Parkinson's Disease Rating
      Scale (UPDRS), timed motor tests, the Schwab and England Activities of Daily
      Living and a diary chart to document motor fluctuations. Alterations in
      parkinsonian signs, motor performance and functional outcome were recorded
      postoperatively (1) under temporary complete withdrawal of both STN stimulation
      and medication; (2) in the presence of STN stimulation only; and (3) in the
      presence of both STN stimulation and medication. The results were compared with
      the preoperative data assessed in defined on-phase and defined off-phase. STN
      stimulation on (compared to STN stimulation off) results in a significant
      improvement in UPDRS motor scores: after 3 months from 50.5 +/- 14.3 to 27.8 +/-
      5.8, and after 12 months from 49.4 +/- 14.1 to 27.1 +/- 7.1 (p < 0.01). There was
      a significant decrease in the average duration of off-periods from 8.82 +/- 2.47
      hours to 1.00 +/- 1.06 hours (p < 0.001), a marked increase in on-periods without
      dyskinesia from 4.62 +/- 2.72 to 14.62 +/- 1.51 hours (p < 0.01), and a sharp
      drop in on-periods with dyskinesia from 2.87 (+/- 4.18) to 0.25 (+/- 0.97) hours
      (p < 0.05), which remained stable up to 12 months (off-periods: 1.25 +/- 1.58
      hours, p < 0.001; on-periods without: 13.87 +/- 1.95 hours, p < 0.001; and on
      periods wth dyskinesia: 0.37 +/- 1.06 hours, p < 0.05). However, our first PD
      patient with an implanted DBS electrode within the STN died from cardiac
      infarction two days after surgery. This sudden death was not linked either to
      surgery nor to stimulation - and happened by chance. Our findings confirm that
      STN stimulation is a suitable functional neurosurgical procedure for the
      modulation and control of PD signs associated with severe motor fluctuations, in
      that they demonstrate a beneficial effect which was fully sustained over a one
      year follow-up period. KEYWORDS: Subthalamic nucleus, deep brain stimulation,
      Parkinson's disease.

PMID- 10907729
TI  - Short-term effect of amantadine sulphate on motor performance and reaction time
      in patients with idiopathic Parkinson's disease.
AB  - In thirty patients with idiopathic Parkinson's disease (PD) we examined in a
      prospectively designed study the effect on motor performance and cognitive
      functions of amantadine sulphate, applied intravenously over a period of 14 days.
      Prior to the introduction of amantadine and post infusionem the motor function
      was measured by the Unified Parkinson Disease Rating Scale (UPDRS) and the Motor
      Performance Test Series (MPS); the simple and the choice reaction time were
      assessed using the Vienna Reaction Unit (VRU). The primary endpoint of efficacy
      was the change in the UPDRS part III (motor examination) after 14 days of
      amantadine sulphate administration compared with baseline. Secondary end-points
      were changes in the variables of-the MPS and VRU at the end of administration
      interval compared with baseline. Overall, after 14 days of intravenous amantadine
      administration (200mg/ day), a significant improvement was obtained in motor
      performance with respect to the semiquantitative motor scores of the UPDRS (p =
      0.002) and the quantitative motor variables in the pertinent subtests of the MPS,
      reflecting precision and speed of arm-hand movement as well as manual and finger
      dexterity, for the right (p < 0.01) and the left hand (p < 0.05). However, all
      patients being viewed collectively, it was observed that there was a widely
      differing time delay of efficient motor response to amantadine from 4 to 9 days
      between individuals, whilst the quality of motor response remained stable for the
      follow-up period. Although simple reaction time showed no significant
      improvement, choice reaction time shortened significantly in less affected PD
      patients staging Hoehn and Yahr I to III (p < 0.05). We conclude that apart from
      efficacy on motor performance, amantadine sulphate - applied intravenously - has
      a positive effect on cognitive functions, particularly in less affected PD
      patients.

PMID- 10907730
TI  - Reduction of dyskinesia and induction of akinesia induced by morphine in two
      parkinsonian patients with severe sciatica.
AB  - In two patients with Parkinson's disease and L-Dopa induced dyskinesia we
      administered morphine orally to alleviate lumboradicular pain unresponsive to any
      other form of treatment. Besides an alleviation of the pain both patients showed
      a decrease in dyskinetic movements at very low doses of morphine and an increase
      in akinesia at higher doses. This observation indicates a modulation of basal
      ganglia output by morphine with the possibility of reducing L-Dopa induced
      dyskinesia in patients treated with morphine for pain.

PMID- 10907731
TI  - The alpha1-antichymotrypsin A-allele in German Parkinson disease patients.
AB  - An increased frequency of the A-allele of the alpha-antichymotrypsin (ACT) gene
      has been recently described in Japanese patients suffering from Parkinson disease
      (PD). In the present study, we have analyzed 62 German PD patients with regard to
      their ACT and APOE genotypes and compared them to 53 controls without clinical or
      pathological evidence of neurodegenerative disease. The A-allele frequency was
      47% in PD patients compared to 54% in control cases excluding ACT as a major
      susceptibility factor for PD in the Caucasian population. Yet, ACT-A allele
      frequencies were significantly different (p < 0.001) between Japanese and German
      controls. Therefore, although our data do not suggest that the alpha1-ACT
      polymorphism is a significant risk factor for the development of PD, a
      consideration of differences in genetic background seems warranted when
      evaluating susceptibility factors for neurodegenerative disease.

PMID- 10907732
TI  - Maintenance ECT in Parkinson's disease.
AB  - Electroconvulsive therapy (ECT) has an anti-Parkinsonian effect. In two cases
      repeated single ECT, i.e. maintenance ECT (MECT), caused different, hitherto
      unreported positive effects. One patient had either severe mental side effects
      from higher L-dopa doses or intolerable parkinsonian symptoms on lower doses.
      MECT entailed a marked improvement in parkinsonian symptoms without mental side
      effects. Another patient with depression as well as Parkinson's disease who
      showed a slight improvement of motor symptoms after a series of ECT presented
      further anti-parkinsonian effects on MECT.

PMID- 10907734
TI  - Piracetam reverses hippocampal membrane alterations in Alzheimer's disease.
AB  - The in vitro effects of piracetam treatment on the fluidity of membranes from the
      hippocampus of Alzheimer's Disease patients (AD) and non-demented controls were
      studied. Hippocampal membranes of AD patients showed a significant lower
      hydrocarbon core fluidity compared with membranes from elderly non-demented
      controls. Preincubation with piracetam enhanced the hydrocarbon core fluidity of
      hippocampal membranes from AD-patients as well as elderly controls in a
      concentration depending fashion, although the effect was more pronounced for the
      AD membranes. In the presence of piracetam, the difference of the membrane
      fluidity between AD and control membranes was not longer apparent.

PMID- 10907733
TI  - Alterations in content and phosphorylation state of cytoskeletal proteins in the
      sciatic nerve during ageing and in Alzheimer's disease.
AB  - Paired helical filaments containing the microtubule-associated protein tau in an
      abnormally high phosphorylated state are one of the major hallmarks of
      Alzheimer's disease. In the central nervous system, this neurofibrillar
      degeneration preferentially affects long-axon projection neurons. In the
      peripheral nervous system largely made up by long-axon neurons, formation of
      paired helical filaments, however, has only rarely been described. In the present
      study, we have analysed alterations in the content and phosphorylation state of
      tau and neurofilament protein in the sciatic nerve during ageing and in
      Alzheimer's disease. The amount of both cytoskeletal proteins remained constant
      during ageing but was significantly reduced in Alzheimer's disease. The
      phosphorylation state of tau protein was elevated during ageing as well as in
      Alzheimer's disease. No indications of a paired helical filament-like aggregation
      of tau were found. It is concluded that during normal ageing and in Alzheimer's
      disease, processes are activated in the peripheral nervous system that induce a
      hyperphosphorylation of tau. Increased phosphorylation of tau in peripheral
      neurons, however, is not necessarily accompanied by the formation of paired
      helical filaments. Analysing principal differences in the expression,
      posttranslational modification and metabolism of tau between central and
      peripheral neurons might, therefore, help to get a better insight into the
      mechanism of paired helical filament formation.

PMID- 10907735
TI  - Inhibitory cartridge synapses in the anterior cingulate cortex of schizophrenics.
AB  - Axon cartridges are the specific terminal structures of GABAergic inhibitory
      chandelier interneurons. Cartridges form axo-axonal synapses with local
      projection neurons, thus modulating the neuronal output of diverse brain areas.
      In order to examine the distribution of cartridges, the anterior cingulate
      cortices from the brains of schizophrenic patients and control persons were
      examined with an antibody against parvalbumin. Axon cartridges were mainly
      located in layers V and VI. In our study, schizophrenic patients showed a
      significantly higher density of axon cartridges than controls. These findings add
      new evidence for disturbances of the circuitry of the anterior cingulate cortex
      in schizophrenia implicating that there may be an elevated inhibitory influence
      on the cortical output of this brain region.

PMID- 10907736
TI  - Alterations in hippocampal and hypothalamic monoaminergic neurotransmitter
      systems after alcohol exposure during all three trimester equivalents in adult
      rats.
AB  - Animal models of Fetal Alcohol Syndrome (FAS) often rely on exposing the
      developing organism to alcohol during either the prenatal or postnatal period
      only. Very few studies have examined brain changes resulting from alcohol
      exposure during both the prenatal and postnatal period, a period which is
      equivalent to all three trimesters in humans. In this study, we examined the
      effects of alcohol exposure during this prolonged period of neural development on
      hippocampal and hypothalamic neurotransmitters in the rat. Pregnant dams were
      intubated with alcohol from gestational day (GD) 1 to GD 22 and then their pups
      were intubated with alcohol from postnatal day (PD) 2 to PD 10. Alcohol-exposed
      rats of both sexes exhibited increased hippocampal noradrenaline (NE)
      concentration compared to intubated and nontreated control animals. Within the
      hypothalamus, alcohol-exposed females but not males exhibited increased NE
      concentration. Hypothalamic serotonin (5-HT) concentration was reduced in both
      alcohol-exposed and intubated-control rats compared to nontreated controls. The
      results suggest that both the hippocampal and hypothalamic NE systems are
      especially vulnerable to alcohol insult that occurs during a period of neural
      development that corresponds to the full human prenatal period. alcohol syndrome,
      hippocampus, hypothalamus,

PMID- 10907737
TI  - Left temporal rhythmic electrical activity: a correlate for psychosis? A case
      report.
AB  - It is well recognized that epileptic patients are at higher risk for acute or
      chronic psychotic states than non-epileptic subjects. Here we present
      intracranial depth electrode recordings during a psychotic episode in a 20-year
      old woman who was referred for presurgical evaluation. Unrelated to her seizures,
      she presented acoustic hallucinations and delusions and became agitated for a
      duration of 18-24 hours. During this period, a new unusual pattern of sharp slow
      waves was seen semi-rhythmically every 2-3 sec from left anterior neocortical
      temporal areas. Her condition responded well to a treatment with Haloperidol, but
      not with Benzodiazepines. Ictal and interictal scalp- and depth-EEG recordings
      outside the psychotic episode as well as MRI-based volumetry, PET, SPECT and
      neuropsychological testing gave evidence of bilateral temporal and frontal
      dysfunction. This case report suggests that psychosis in epileptic patients may
      be based on a bilateral cerebral dysfunction linked together in a pathological
      network, but with a focal (here: left temporal) driving mechanism.

PMID- 10907738
TI  - Inositol addition does not improve depression in SSRI treatment failures.
AB  - Some antidepressants, such as Lithium, can augment the antidepressant effect of
      serotonin selective uptake inhibitors (SSRI) in patients who have failed to
      respond to SSRI. Inositol has demonstrated antidepressant effects but in a
      controlled double blind augmentation trial did not improve depression in SSRI
      treatment failures.

PMID- 10907739
TI  - Effects of N7-methylation, N7-platination, and C8-hydroxylation of guanine on H
      bond formation with cytosine: platinum coordination strengthens the Watson-Crick
      pair.
AB  - The hydrogen bonding properties of 1-methylcytosine (1-MeC) with the following
      guanine base derivatives have been studied in DMSO-d6, applying concentration
      dependent 1H NMR spectroscopy: 9-ethylguanine, 7,9-dimethylguanine (7,9-DimeGH+),
      and 7,8-dihydro-8-oxo-9-methylguanine (8-O-9-MeGH), as well as three 9
      ethylguanine complexes carrying different Pt(II) moieties at the N7 position. The
      association constants K for the Watson-Crick pairing schemes are by a factor 2-3
      higher in the cases of platinated guanine complexes compared to the Watson-Crick
      pair between 9-ethylguanine and 1-methylcytosine (K = 6.9 +/- 1.3 M(-1)). Similar
      enhanced stabilities are observed for the pairs formed between 1-MeC and 7,9
      DimeGH+ or 8-O-9-MeGH. The increase in N1H acidity of the guanine derivative upon
      modification at the N7 or C8 positions can be correlated with the association
      constants K; the result is a bell-shaped curve meaning that acidification
      initially stabilizes hydrogen bond formation up to a certain maximum; further
      acidification then leads to a destabilization. For two of the examples studied in
      solution, hydrogen bonding according to Watson-Crick between N7-platinated 9
      ethylguanine and 1-methylcytosine has also been established by X-ray
      crystallography.

PMID- 10907740
TI  - Kinetics and mechanism for reduction of anticancer-active tetrachloroam(m)ine
      platinum(IV) compounds by glutathione.
AB  - Glutathione (GSH) reduction of the anticancer-active platinum(IV) compounds trans
      [PtCl4(NH3)(thiazole)] (1), trans-[PtCl4(cha)(NH3)] (2), cis-[PtCl4(cha)(NH3)]
      (3) (cha=cyclohexylamine), and cis-[PtCl4(NH3)2] (4) has been investigated at 25
      degrees C in a 1.0 M aqueous medium at pH 2.0-5.0 (1) and 4.5-6.8 (2-4) using
      stopped-flow spectrophotometry. The redox reactions follow the second-order rate
      law d[Pt(IV)]/dt=k[GSH]tot[Pt(IV)], where k is a pH-dependent rate constant and
      [GSH]tot the total concentration of glutathione. The reduction takes place via
      parallel reactions between the platinum(IV) complexes and the various protolytic
      species of glutathione. The pH dependence of the redox kinetics is ascribed to
      displacement of these protolytic equilibria. The thiolate species GS is the major
      reductant under the reaction conditions used. The second-order rate constants for
      reduction of compounds 1-4 by GS- are (1.43 +/- 0.01) x 10(7), (3.86 +/- 0.03) x
      10(6), (1.83 +/- 0.01) x 10(6), and (1.18 +/- 0.01) x 10(6) M(-1)s(-1),
      respectively. Rate constants for reduction of 1 by the protonated species GSH are
      more than five orders of magnitude smaller. The mechanism for the reductive
      elimination reactions of the Pt(IV) compounds is proposed to involve an attack by
      glutathione on one of the mutually trans coordinated chloride ligands, leading to
      two-electron transfer via a chloride-bridged activated complex. The kinetics
      results together with literature data indicate that platinum(IV) complexes with a
      trans Cl-Pt-Cl axis are reduced rapidly by glutathione as well as by ascorbate.
      In agreement with this observation, cytotoxicity profiles for such complexes are
      very similar to those for the corresponding platinum(II) product complexes. The
      rapid reduction within 1 s of the platinum(IV) compounds with a trans Cl-Pt-C1
      axis to their platinum(II) analogs does not seem to support the strategy of using
      kinetic inertness as a parameter to increase anticancer activity, at least for
      this class of compounds.

PMID- 10907741
TI  - Enzyme-like effect of metmyoglobin on the thermal cis-trans isomerization of
      stilbazolium betaine.
AB  - A photochromic compound, stilbazolium betaine M, when associated with
      metmyoglobin undergoes an accelerated thermal cis-trans isomerization. A study of
      the pH and ionic strength dependence of the isomerization reaction rate of the
      photochrome associated with metmyoglobin was performed. A comparative
      investigation of the reaction carried out in the presence of three proteins,
      metmyoglobin, apomyoglobin, and human albumin, indicates a specific influence of
      the heme pocket environment on the reaction. Possible mechanisms of the reaction
      acceleration are considered.

PMID- 10907742
TI  - Spectroscopic studies of the tungsten-containing formaldehyde ferredoxin
      oxidoreductase from the hyperthermophilic archaeon Thermococcus litoralis.
AB  - The electronic and redox properties of the iron-sulfur cluster and tungsten
      center in the as-isolated and sulfide-activated forms of formaldehyde ferredoxin
      oxidoreductase (FOR) from Thermococcus litoralis (Tl) have been investigated by
      using the combination of EPR and variable-temperature magnetic circular dichroism
      (VTMCD) spectroscopies. The results reveal a [Fe4S4]2+,+ cluster (Em=-368mV) that
      undergoes redox cycling between an oxidized form with an S=0 ground state and a
      reduced form that exists as a pH- and medium-dependent mixture of S=3/2 (g=5.4;
      E/D=0.33) and S=1/2 (g=2.03, 1.93, 1.86) ground states, with the former
      dominating in the presence of 50% (v/v) glycerol. Three distinct types of W(V)
      EPR signals have been observed during dye-mediated redox titration of as-isolated
      Tl FOR. The initial resonance observed upon oxidation, termed the "low-potential"
      W(V) species (g=1.977, 1.898, 1.843), corresponds to approximately 25-30% of the
      total W and undergoes redox cycling between W(IV)/ W(V) and W(V)/W(VI) states at
      physiologically relevant potentials (Em= -335 and -280 mV, respectively). At
      higher potentials a minor "mid-potential" W(V) species, g= 1.983, 1.956, 1.932,
      accounting for less than 5 % of the total W, appears with a midpoint potential of
      -34 mV and persists up to at least + 300 mV. At potentials above 0 mV, a major
      "high-potential" W(V) signal, g= 1.981, 1.956, 1.883, accounting for 30-40% of
      the total W, appears at a midpoint potential of +184 mV. As-isolated samples of
      Tl FOR were found to undergo an approximately 8-fold enhancement in activity on
      incubation with excess Na2S under reducing conditions and the sulfide-activated
      Tl FOR was partially inactivated by cyanide. The spectroscopic and redox
      properties of the sulfide-activated Tl FOR are quite distinct from those of the
      as-isolated enzyme, with loss of the low-potential species and changes in both
      the mid-potential W(V) species (g= 1.981, 1.950, 1.931; Em = -265 mV) and high
      potential W(V) species (g=1.981, 1.952, 1.895; Em = +65 mV). Taken together, the
      W(V) species in sulfide-activated samples of Tl FOR maximally account for only
      15% of the total W. Both types of high-potential W(V) species were lost upon
      incubation with cyanide and the sulfide-activated high-potential species is
      converted into the as-isolated high-potential species upon exposure to air.
      Structural models are proposed for each of the observed W(V) species and both
      types of mid-potential and high-potential species are proposed to be artifacts of
      ligand-based oxidation of W(VI) species. A W(VI) species with terminal sulfido or
      thiol ligands is proposed to be responsible for the catalytic activity in sulfide
      activated samples of Tl FOR.

PMID- 10907743
TI  - Obtaining ligand geometries from paramagnetic shifts in low-spin haem proteins.
AB  - Previously, the theoretical relationship between paramagnetic chemical shifts and
      the axial ligands in low-spin haem proteins has been tested extensively in haems
      b and c with His, Met, and cyanide ligands. Variations in the electronic
      structure of the haem and the magnetic susceptibility tensors have been shown to
      depend primarily on the axial ligand geometry, and the shifts of haem
      substituents have been used to obtain the first structural information for
      several cytochromes. Recently, the database of assigned spectra for bis-His haems
      has been extended sufficiently for an empirical equation to be produced for
      treating 1H NMR data from haem methyl groups at 298 K. However, the database used
      contains large systematic deviations and the form of the equation leads to
      systematic errors in the ligand geometries. This article describes the link with
      the semi-empirical methods used previously and provides a set of corrected
      empirical parameters as well as an improved equation. The possibilities for
      generalising the empirical method to account for ligands other than His and
      temperatures other than 298 K are discussed.

PMID- 10907744
TI  - Kinetics and thermodynamics of peroxidase- and laccase-catalyzed oxidation of N
      substituted phenothiazines and phenoxazines.
AB  - Steady-state and single-turnover kinetics for the oxidation of the N-substituted
      phenothiazines (PTs) and phenoxazines (POs) catalyzed by fungal Coprinus cinereus
      peroxidase and Polyporus pinsitus laccase were investigated at pH 4-10. In the
      case of peroxidase, an apparent bimolecular rate constant (expressed as
      k(cat)/K(m)) varied from 1 x10(7)M(-1)s(-1) to 2.6 x 108 M(-1)s(-1) at pH 7.0.
      The constants for PO oxidation were higher in comparison to PT. pH dependence
      revealed two or three ionizable groups with pKa values of 4.9-5.7 and 7.7-9.7
      that significantly affected the activity of peroxidase. Single-turnover
      experiments showed that the limiting step of PT oxidation was reduction of
      compound II and second-order rate constants were obtained which were consistent
      with the constants at steady-state conditions. Laccase-catalyzed PT and PO
      oxidation rates were lower; apparent bimolecular rate constants varied from 1.8x
      10(5) M(-1) s(-1) to 2.0 x 10(7) M(-1) s(-1) at pH 5.3. PO constants were higher
      in comparison to PT, as was the case with peroxidase. The dependence of the
      apparent bimolecular constants of compound II or copper type 1 reduction, in the
      case of peroxidase or laccase, respectively, was analyzed in the framework of the
      Marcus outer-sphere electron-transfer theory. Peroxidase-catalyzed reactions with
      PT, as well as PO, fitted the same hyperbolic dependence with a maximal oxidation
      rate of 1.6 x 10(8)M(-1)s(-1) and a reorganization energy of 0.30 eV. The
      respective parameters for laccase were 5.0 x 10(7) M(-1) s(-1) and 0.29 eV.

PMID- 10907745
TI  - Major changes in copper coordination accompany reduction of peptidylglycine
      monooxygenase: implications for electron transfer and the catalytic mechanism.
AB  - X-ray absorption spectroscopy has been used to probe the local coordination of
      the copper centers in the oxidized and reduced states of the peptidylglycine
      monooxygenase catalytic core (PHMcc) in both the resting and substrate-bound
      forms of the enzyme. The results indicate that reduction causes significant
      changes in coordination number and geometry of both Cu centers (CuH and CuM). The
      CuH center changes from 4- or 5-coordinate tetragonal to a 2-coordinate
      configuration, with one of the three histidine ligands becoming undetectable by
      EXAFS (suggesting that it has moved away from the CuH by at least 0.3 A). The CuM
      center changes from 4- or 5-coordinate tetragonal to a trigonal or tetrahedral
      configuration, with an estimated 0.3-0.5 A movement of the M314 S ligand.
      Reduction also leads to loss of coordinated water from both of the coppers.
      Substrate binding has little or no effect on the local environment of the Cu
      centers in either oxidation state. These findings bring into question whether
      direct electron transfer between CuH and CuM via a tunneling mechanism can be
      fast enough to support the observed catalytic rate, and suggest that some other
      mechanism for electron transfer, such as superoxide channeling, should be
      considered.

PMID- 10907746
TI  - Interaction of nitric oxide with the oxygen evolving complex of photosystem II
      and manganese catalase: a comparative study.
AB  - We compare the interaction of nitric oxide with the S states of the oxygen
      evolving complex (OEC) of photosystem II and the dinuclear Mn cluster of Thermus
      thermophilus catalase. Flash fluorescence studies indicate that the S3 state of
      the OEC in the presence of ca. 0.6 mM NO is reduced to the S1 with an apparent
      halftime of ca. 0.4 s at about 18 degrees C, compared with a biphasic decay, with
      approximate halftimes of 28 s for S3 to S2 and 140 s for S2 to S1 in the absence
      of NO. Under similar conditions the S2 state is reduced by NO to the S1 state
      with an approximate halftime of 2 s. These results extend a recent study
      indicating a slow reduction of the S1 state at -30 degrees C, via the S0 and S(
      1) states, to a Mn(II)-Mn(III) state resembling the corresponding state in
      catalase. The reductive mode of action of NO is repeated with the di-Mn cluster
      of catalase: the Mn(III)-Mn(III) redox state is reduced to the Mn(II)-Mn(II)
      state via the intermediate Mn(II)-Mn(III) state. The kinetics of this reduction
      suggest a decreasing reduction potential with decreasing oxidation state, similar
      to what is observed with the active states of the OEC. What is unique about the
      OEC is the rapid interaction of NO with the S3 state of the OEC, which is
      compatible with a metalloradical character of this state.

PMID- 10907747
TI  - Steric control of DNA interstrand cross-link sites of trans platinum complexes:
      specificity can be dictated by planar nonleaving groups.
AB  - Recent findings that novel trans-dichloroplatinum(II) complexes exhibit antitumor
      activity violate the classical structure-activity relationships of platinum(II)
      complexes. These novel "nonclassical" trans platinum complexes also comprise
      those containing planar aromatic amines. Initial studies have shown that these
      compounds form a considerable amount of DNA interstrand cross-links (up to
      approximately 30%) with a rate markedly higher than clinically ineffective
      transplatin. The present work has shown, using Maxam-Gilbert footprinting, that
      trans-[PtCl2(NH3)(quinoline)] and trans-[PtCl2(NH3)(thiazole)], representatives
      of the group of new antitumor trans-dichloroplatinum complexes containing planar
      amines, preferentially form DNA interstrand cross-links between guanine residues
      at the 5'-GC-3' sites. Thus, DNA interstrand cross-linking by trans
      [PtCl2(NH3)(quinoline)] and trans-[PtCl2(NH3)(thiazole)] is formally equivalent
      to that by antitumor cisplatin, but different from clinically ineffective
      transplatin which preferentially forms these adducts between complementary
      guanine and cytosine residues. This result shows for the first time that simple
      chemical modification of the structure of an inactive compound alters its DNA
      binding site into a DNA adduct of an active drug.

PMID- 10907748
TI  - Investigation of exchange couplings in [Fe3S4]+ clusters by electron spin-lattice
      relaxation.
AB  - We have studied four proteins containing oxidized 3Fe clusters ([Fe3S4]+, S=1/2,
      composed of three, antiferromagnetically coupled high-spin ferric ions) by
      continuous wave (CW) and pulsed EPR techniques: Azotobacter vinelandii ferredoxin
      I, Desulfovibrio gigas ferredoxin II, and the 3Fe forms of Pyrococcus furiosus
      ferredoxin and aconitase. The 35 GHz (Q-band) CW EPR signals are simulated to
      yield experimental g tensors, which either had not been reported, or had been
      reported only at X-band microwave frequency. Pulsed X- and Q-band EPR techniques
      are used to determine electron spin-lattice (T1, longitudinal) relaxation times
      at several positions on the samples' EPR envelope over the temperature range 2
      4.2 K. The T1, values vary sharply across the EPR envelope, a reflection of the
      fact that the envelope results from a distribution in cluster properties, as seen
      earlier as a distribution in g3 values and in 57 Fe hyperfine interactions, as
      detected by electron nuclear double resonance spectroscopy. The temperature
      dependence of 1/T1 is analyzed in terms of the Orbach mechanism, with relaxation
      dominated by resonant two-phonon transitions to a doublet excited state at
      approximately 20 cm(-1) above the doublet ground state for all four of these 3Fe
      proteins. The experimental EPR data are combined with previously reported 57Fe
      hyperfine data to determine electronic spin exchange-coupling within the
      clusters, following the model of Kent et al. Their model defines the coupling
      parameters as follows: J13=J, J12=J(1+epsilon'), J23=J(1+epsilon), where Jij is
      the isotropic exchange coupling between ferric ions i and j, and epsilon' and
      epsilon' are measures of coupling inequivalence. We have extended their theory to
      include the effects of epsilon' not equal to 0 and thus derived an exact
      expression for the energy of the doublet excited state for any epsilon, epsilon'.
      This excited state energy corresponds roughly to epsilonJ and is in the range 5
      10 cm(-1) for each of these four 3Fe proteins. This magnitude of the product
      epsilonJ, determined by our time-domain relaxation studies in the temperature
      range 2-4 K, is the same as that obtained from three other distinct types of
      study: CW EPR studies of spin relaxation in the range 5.5-50 K, NMR studies in
      the range 293-303 K, and static susceptibility measurements in the range 1.8-200
      K. We suggest that an apparent disagreement as to the individual values of J and
      epsilon be resolved in favor of the values obtained by susceptibility and NMR (J
      > or approximately 200 cm(-1) and epsilon> or =0.02 cm(-1)). as opposed to a
      smaller J and larger r as suggested in CW EPR studies. However, we note that this
      resolution casts doubt on the accepted theoretical model for describing the
      distribution in magnetic properties of 3Fe clusters.

PMID- 10907749
TI  - Paramagnetic 1H NMR spectroscopy of the reduced, unbound photosystem I subunit
      PsaC: sequence-specific assignment of contact-shifted resonances and
      identification of mixed- and equal-valence Fe-Fe pairs in [4Fe-4S] centers FA-
      and FB-.
AB  - The PsaC subunit of Photosystem I (PS I) is a 9.3-kDa protein that binds two
      important cofactors in photosynthetic electron transfer: the [4Fe-4S] clusters FA
      and FB. The g-tensor orientation of FA- and FB- is believed to be correlated to
      the preferential localization of the mixed-valence and equal-valence (ferrous)
      iron pairs in each [4Fe-4S]+ cluster. The preferential position of the mixed
      valence and equal-valence pairs, in turn. can be inferred from the study of the
      temperature dependence of contact-shifted resonances by 1H NMR spectroscopy. For
      this, a sequence-specific assignment of these signals is required. The 1H NMR
      spectrum of reduced, unbound PsaC from Synechococcus sp. PCC 7002 at 280.4 K in
      99% D2O solution shows 18 hyperfine-shifted resonances. The non-solvent
      exchangeable, hyperfine-shifted resonances of reduced PsaC are clearly identified
      as belonging to the cysteines coordinating the clusters FA- and FB- by their
      downfield chemical shifts, by their temperature dependencies, and by their short
      T1 relaxation times. The usual fast method of assigning the 1H NMR spectra of
      reduced [4Fe-4S] proteins through magnetization transfer from the oxidized to the
      reduced state was not feasible in the case of reduced PsaC. Therefore, a de novo
      self-consistent sequence-specific assignment of the hyperfine-shifted resonances
      was obtained based on dipolar connectivities from 1D NOE difference spectra and
      on longitudinal relaxation times using the X-ray structure of Clostridium acidi
      urici 2[4Fe-4S] cluster ferredoxin at 0.94 A resolution as a model. The results
      clearly show the same sequence-specific distribution of Curie and anti-Curie
      cysteines for unbound, reduced PsaC as established for other [4Fe-4S]-containing
      proteins; therefore, the mixed-valence and equal-valence (ferrous) Fe-Fe pairs in
      FA- and FB- have the same preferential positions relative to the protein. The
      analysis reveals that the magnetic properties of the two [4Fe-4S] clusters are
      essentially indistinguishable in unbound PsaC, in contrast to the PsaC that is
      bound as a component of the PS I complex.

PMID- 10907750
TI  - Optical and TDPAC spectroscopy of Hg(II)-rubredoxin: model for a mononuclear
      tetrahedral [Hg(CysS)4]2- center. ISOLDE Collaboration.
AB  - Rubredoxins possess a well-defined mononuclear tetrahedral tetrathiolate metal
      binding site, a feature exploited by several investigations to study the
      spectroscopic characteristics and the coordination chemistry of different metal
      ions at this binding site. In the present work, Hg(II)-substituted rubredoxin
      (Rd) from Desulfovibrio gigas has been studied by electronic absorption, circular
      dichroism (CD), magnetic circular dichroism (MCD), and time differential
      perturbed angular correlation of gamma-rays (TDPAC) spectroscopies. The TDPAC
      spectrum of 199mHg-Rd at pH 8 exhibits a prevailing nuclear quadrupole
      interaction (NQI) with a precession frequency of omega1=0.09 Grad/s and an
      asymmetry parameter eta=0, features characteristic of a slightly distorted
      tetrahedral tetrathiolate metal coordination, i.e, a HgCysS4 center. In addition,
      three minor populated NQIs have also been detected. They may represent a trigonal
      HgS3 (omega1=1.13 Grad/s, eta=0.21), a digonal HgS2 (omega1= 1.34 Grad/s, eta
      =0.20), and a digonal Hg(II) coordination (omega = 1.58 Grad/s, eta =0.18) with
      unidentified ligands. Since similar studies at pH 2.5 revealed a time-dependent
      increase of the HgCysS4 population, the low populated sites may represent
      intermediate Hg(II) complexes formed prior to the generation of the
      thermodynamically stable structure. The metal-induced absorption envelope of Hg
      Rd reveals three distinct transitions with Gaussian-resolved maxima located at
      230, 257, and 284 nm, which are paralleled by dichroic features in the
      corresponding difference CD spectrum of Hg(II)-Rd versus apo-Rd. Based on the
      optical electronegativity theory of J*rgensen, the lowest energy transition has
      been attributed to a CysS-Hg(II) charge-transfer excitation. The Td type of metal
      coordination in Hg-Rd is supported by the presence of an unresolved A-term with a
      negative lobe at 295 nm in the difference MCD spectrum. These results point to
      the usefulness of optical and TDPAC spectroscopies for studying Hg(II) sites in
      other proteins.

PMID- 10907751
TI  - Recombinant superoxide dismutase from a hyperthermophilic archaeon, Pyrobaculum
      aerophilium.
AB  - Superoxide dismutase (SOD) from the hyperthermophilic archaeon Pyrobaculum
      aerophilum (a facultative aerobe) has been cloned and expressed in a mesophilic
      host (Escherichia coli) as a soluble tetrameric apoprotein. The purified
      apoprotein can be reconstituted with either Mn or Fe by heating the protein with
      the appropriate metal salt at an elevated temperature (95 degrees C). Both Mn-
      and Fe-reconstituted P. aerophilum SOD exhibit superoxide dismutase activity,
      with the Mn-containing enzyme having the higher activity. P. aerophilum SOD is
      extremely thermostable and the reconstitution with Mn(II) can be performed in an
      autoclave (122 degrees C, 18 psi). The Mn(III) optical absorption spectrum of Mn
      reconstituted P. aerophilum SOD is distinct from that of most other MnSODs and is
      unchanged upon addition of NaN3. The optical absorption spectrum of Fe
      reconstituted P. aerophilum SOD is typical of Fe-substituted MnSODs and authentic
      FeSOD and exhibits a pH-dependent transition with an effective pKa value higher
      than that found for Fe-substituted MnSOD from either E. coli or Thermus spp.
      Amino acid sequence analysis shows that the P. aerophilum SOD is closely related
      to SODs from other hyperthermophilic archaea (Aeropyrum pernix and Sulfolobus
      spp.), forming a family of enzymes distinct from the hyperthermophilic bacterial
      SOD from Aquifex pyrophilus and from mesophilic SODs.

PMID- 10907752
TI  - Progress report on molecular biometallics (1996-2000), a project of the priority
      areas for research under the auspices of the Japanese Government.

PMID- 10907753
TI  - Measures of reliability in sports medicine and science.
AB  - Reliability refers to the reproducibility of values of a test, assay or other
      measurement in repeated trials on the same individuals. Better reliability
      implies better precision of single measurements and better tracking of changes in
      measurements in research or practical settings. The main measures of reliability
      are within-subject random variation, systematic change in the mean, and retest
      correlation. A simple, adaptable form of within-subject variation is the typical
      (standard) error of measurement: the standard deviation of an individual's
      repeated measurements. For many measurements in sports medicine and science, the
      typical error is best expressed as a coefficient of variation (percentage of the
      mean). A biased, more limited form of within-subject variation is the limits of
      agreement: the 95% likely range of change of an individual's measurements between
      2 trials. Systematic changes in the mean of a measure between consecutive trials
      represent such effects as learning, motivation or fatigue; these changes need to
      be eliminated from estimates of within-subject variation. Retest correlation is
      difficult to interpret, mainly because its value is sensitive to the
      heterogeneity of the sample of participants. Uses of reliability include decision
      making when monitoring individuals, comparison of tests or equipment, estimation
      of sample size in experiments and estimation of the magnitude of individual
      differences in the response to a treatment. Reasonable precision for estimates of
      reliability requires approximately 50 study participants and at least 3 trials.
      Studies aimed at assessing variation in reliability between tests or equipment
      require complex designs and analyses that researchers seldom perform correctly. A
      wider understanding of reliability and adoption of the typical error as the
      standard measure of reliability would improve the assessment of tests and
      equipment in our disciplines.

PMID- 10907754
TI  - Energy cost calculations for exercise prescription: an update.
AB  - Recent research has resulted in a number of recommended changes in how fitness
      professionals should prescribe target workloads and calculate the energy cost of
      exercise. The principal changes are in the use of oxygen consumption reserve
      (VO2R) as an alternative to percentage of maximal oxygen consumption (VO2max) for
      prescribing exercise intensity, the use of net VO2 rather than gross VO2 for the
      calculation of caloric expenditure during exercise, and a modification of the
      American College of Sports Medicine (ACSM) equation for calculating the oxygen
      cost of leg cycle ergometry. The VO2R method of prescribing exercise workloads is
      similar to the heart rate reserve (HRR) method of prescribing target heart rates,
      i.e. the target workload is established at a given percentage of the difference
      between maximal and resting VO2. Several recent studies have shown that there is
      a discrepancy between the exercise intensity at given percentages of HRR and
      VO2max, but that HRR and VO2R yield equivalent exercise intensities. The use of
      VO2R in exercise prescription provides more accurate target workloads, especially
      for individuals with a low fitness level. Net VO2 during exercise is that amount
      above resting VO2 due to the exercise itself. A recent recommendation is to
      employ net VO2 in the calculation of the caloric expenditure during exercise, so
      as not to overestimate potential bodyweight loss. Several recent studies of leg
      cycling ergometry have yielded equations for the estimation of VO2 that include a
      term for unloaded cycling, i.e. the oxygen cost of moving the legs against zero
      resistance. The equations from these studies provide more accurate estimations of
      cycling VO2 than the existing ACSM equation, and a new standardised equation has
      been developed and adopted by the ACSM. The new equation is especially useful for
      improving the accuracy of VO2 estimates during low intensity leg cycle ergometry.
      The ACSM equation for bench stepping has also been modified to include a term for
      resting metabolism.

PMID- 10907755
TI  - Ramp exercise protocols for clinical and cardiopulmonary exercise testing.
AB  - Historically, the protocol used for exercise testing has been based on tradition,
      convenience or both. In the 1990s, a considerable amount of research has focused
      on the effect of the exercise protocol on test performance, including exercise
      tolerance, diagnostic accuracy, gas exchange patterns and the accuracy with which
      oxygen uptake (VO2) is predicted from the work rate. Studies have suggested that
      protocols which contain large and/or unequal increments in work cause a
      disruption in the normal linear relation between VO2 and work rate, leading to an
      overprediction of metabolic equivalents. Other studies have demonstrated that
      such protocols can mask the salutary effects of an intervention, and some have
      suggested that the protocol design can influence the diagnostic performance of
      the test. Guidelines published by major organisations have therefore suggested
      that the protocol be individualised based on the patient being tested and the
      purpose of the test. The ramp approach to exercise testing has recently been
      advocated because it facilitates recommendations made in these guidelines. This
      article reviews these issues and discusses the evolution of ramp testing which
      has occurred in the 1990s.

PMID- 10907756
TI  - A review of the concept of the heart rate deflection point.
AB  - The heart rate deflection point (HRDP) is a downward or upward change from the
      linear HR-work relationship evinced during progressive incremental exercise
      testing. The HRDP is reported to be coincident with the anaerobic threshold. In
      1982, Conconi and colleagues suggested that this phenomenon could be used as a
      noninvasive method to assess the anaerobic threshold. These researchers developed
      a field test to assess the HRDP, which has become popularised as the 'Conconi
      test'. Concepts used to define and assess the anaerobic threshold as well as
      methodological procedures used to determine the HRDP are diverse in the
      literature and have contributed to controversy surrounding the HRDP concept.
      Although the HRDP may be assessed in either field or laboratory settings, the
      degree of HR deflection is highly dependent upon the type of protocol used. The
      validity of HRDP to assess the anaerobic threshold is uncertain, although a high
      degree of relationship exists between HRDP and the second lactate turnpoint. The
      HRDP appears to be reliable when a positive identification is made; however, not
      all studies report 100% reproducibility. Although the physiological mechanisms
      explaining the HRDP are unresolved, a relationship exists between the degree and
      direction of HRDP and left ventricular function. The HRDP has potential to be
      used for training regulation purposes. Clinically, it may be incorporated to set
      exercise intensity parameters for cardiac rehabilitation.

PMID- 10907758
TI  - Injury toll following the 1997 Maccabiah Games bridge collapse: implications of
      major disasters for sports medicine teams.
AB  - A major disaster was encountered at the 1997 Maccabiah Games in Israel. As the
      Australian team was about to enter the main stadium for the opening ceremony, a
      pedestrian bridge they were crossing collapsed, killing 4 athletes and injuring
      many others. The aim of this paper is to establish the rates, types and
      anatomical locations of musculoskeletal injuries incurred by members of the
      Australian Maccabiah Games team, with particular reference to the impact of the
      bridge collapse. In total, the 410 members of the team (360 athletes and coaches
      and 50 team officials) reported 166 injuries from their participation in sport
      and 30 musculoskeletal injuries associated with the collapse of the bridge. The
      most common sports-related injuries were sprains and strains to the hip/thigh,
      lumbar spine and ankle/foot regions, while the bridge collapse resulted in, most
      commonly, sprains and contusions to the hip/thigh, knee, lower leg and ankle/foot
      regions. In addition, team members incurred many medical and psychological
      conditions. This paper makes several recommendations for sports medicine staff
      based on the experience of this significant sport disaster.

PMID- 10907759
TI  - Health sector reform: scourge or salvation for TB control in developing
      countries?

PMID- 10907760
TI  - Tuberculosis in times of health sector reform.

PMID- 10907757
TI  - Exercise-induced arterial hypoxaemia in athletes: a review.
AB  - During exercise, healthy individuals are able to maintain arterial oxygenation,
      whereas highly-trained endurance athletes may exhibit an exercise-induced
      arterial hypoxaemia (EIAH) that seems to reflect a gas exchange abnormality. The
      effects of EIAH are currently debated, and different hypotheses have been
      proposed to explain its pathophysiology. For moderate exercise, it appears that a
      relative hypoventilation induced by endurance training is involved. For high
      intensity exercise, ventilation/perfusion (V(A)/Q) mismatching and/or diffusion
      limitation are thought to occur. The causes of this diffusion limitation are
      still under debate, with hypotheses being capillary blood volume changes and
      interstitial pulmonary oedema. Moreover, histamine is released during exercise in
      individuals exhibiting EIAH, and questions persist as to its relationship with
      EIAH and its contribution to interstitial pulmonary oedema. Further
      investigations are needed to better understand the mechanisms involved and to
      determine the long term consequences of repetitive hypoxaemia in highly trained
      endurance athletes.

PMID- 10907761
TI  - Advancing tuberculosis control within reforming health systems.
AB  - In developing nations, diverse health reform programs are affecting the design,
      financing and delivery of health care services as well as public health practice.
      This paper summarizes the characteristics of major reform strategies seeking to
      improve efficiency, equity and quality. Opportunities and risks for tuberculosis
      control are identified, as are responses in managing the reform transition.
      Recommendations are provided to advance tuberculosis control in this dynamic
      environment. These include participation in the planning process; demonstration
      of synergy between reform objectives and tuberculosis control; articulation of
      core functions to be protected; technical, managerial and leadership capacity
      building; documentation of effects and best practices; and collaboration with
      those pursuing other public health priorities and reform analysis.

PMID- 10907762
TI  - Health sector reform and tuberculosis control: the case of Zambia.
AB  - SETTING: Zambia, 1995-1997. OBJECTIVE: To describe the process leading to the
      collapse of Zambia's National Tuberculosis Programme NTP). DESIGN: A descriptive
      analysis of health sector reform in Zambia and its effects on the NTP during the
      period 1995-1997. RESULTS: By the end of 1997 the NTP had stopped functioning.
      The main reason was that external support had ended, while the National Strategic
      Health Plan 1995-1999 had no budget for special programmes according to the
      policy to integrate these into the general health services. As a consequence,
      technical support for tuberculosis control to districts ended as staff was
      reduced to one officer responsible for the national coordination of AIDS/HIV,
      sexually transmitted diseases (STD), tuberculosis and leprosy. The most serious
      effect of the transition was the interruption of supplies of anti-tuberculosis
      drugs in 1998. CONCLUSIONS: The experience in Zambia demonstrates the urgent need
      for constructive dialogue between 'health reformers' and 'disease controllers'.
      The aim of this dialogue would be to develop a model that ensures that
      tuberculosis patients are properly diagnosed and cured in countries that are
      embarking on a reform of their health services.

PMID- 10907763
TI  - Tuberculosis and health sector reform in Bangladesh.
AB  - In 1998 the Government of Bangladesh changed its health and population sector
      strategy from a project-oriented approach (the Fourth Population and Health
      Project--FPHP) to sector-wide management (the Fifth Health and Population Sector
      Programme--HPSP). This article describes the development and achievements of the
      tuberculosis programme during the FPHP, and discusses the potential opportunities
      and challenges anticipated by the programme from the reformed health service
      delivery of the HPSP. 'Further strengthening of tuberculosis and leprosy control
      services' was one of the 66 projects of the FPHP. As part of the FPHP, the
      National Tuberculosis Programme policy was revised in 1992 and the project was
      implemented in phases. By mid 1998, 90% of the population was covered, and more
      than 200,000 tuberculosis cases had been diagnosed and treated with 80% success.
      We describe the reasons for this success and analyse the pitfalls of the project.
      The objective of the reforms in HPSP is to provide cost-effective, sustainable,
      quality services to those in need through an essential service package that
      includes control of communicable diseases such as tuberculosis and leprosy.
      Tuberculosis services will become more accessible as community clinics deliver
      essential health services for every 6000 population. Non-public health care
      providers, who contribute significantly to health services in the country, will
      be involved in service delivery. The main challenge is to maintain the quality of
      successful projects, such as tuberculosis control, during the transition period.

PMID- 10907764
TI  - Health sector reform in Brazil: impact on tuberculosis control.
AB  - This paper comments on the reform process of the health sector policies that took
      place after 1986 in Brazil, and its negative impact on the National Tuberculosis
      Control Programme (NTP). Decentralisation was followed by a slow transition from
      a vertical programme to an integrated programme. In 1990, the NTP was dismantled
      due to fiscal constraints, and in 1992, the NTP component was reorganised, with
      national and regional coordinators and subsequent increased support to state
      programmes. In 1996, the health sector reform continued its process, but this
      consisted mainly of cuts in health budgets and rapid decentralisation from
      federal level to unprepared states and municipalities, leading to the weakening
      of local tuberculosis control programmes. Only recently has government commitment
      been secured, with a new National Plan on Tuberculosis Control which includes the
      World Health Organization strategy for TB control--the implementation of the DOTS
      strategy (directly-observed treatment, short-course)--and efforts are being
      concentrated in 5500 municipalities. The programme has a centralised
      administration which supports decentralised implementation through out-patient
      clinics, and resources will be focused on local service delivery.

PMID- 10907765
TI  - Effective tuberculosis control and health sector reforms in Kenya: challenges of
      an increasing tuberculosis burden and opportunities through reform.
AB  - During the period from 1980 to 1997, the annual number of new tuberculosis cases
      increased four-fold in Kenya, and had reached approximately 50,000 cases by 1998.
      During the same time period, the government per capita expenditure on health
      dropped from US$9.5 to US$3.5. Since 1983, Kenya has been decentralising
      financial responsibility and decision-making power to the districts. In addition,
      the late 1980s saw the introduction of cost-sharing schemes for most health
      services, excluding tuberculosis (TB) treatment. In the midst of these changes, a
      dual epidemic of TB and HIV/AIDS emerged, and is presently over-burdening the
      traditional public health system. In response, the National Leprosy and
      Tuberculosis Control Programme (NLTP) is seeking a wider network of service
      providers and new approaches to the prevention and treatment of TB in the
      country. The history of health sector reform in Kenya is summarised and the role
      of the NLTP in these reforms assessed. Recent approaches taken by the NLTP to
      sustain effective TB control, which draw on the environment of a changing and
      flexible health system, are expressed. Participation of the NLTP in components of
      health sector reform, particularly decentralisation, integration, financing
      through cost-sharing and public/private mix, are highlighted.

PMID- 10907766
TI  - Spirometry and tests of bronchial hyperresponsiveness in population studies.
AB  - The use of spirometry in epidemiological studies has provided objective evidence
      of the acute and chronic effects of occupational and environmental exposure to
      many agents as well as data on exposure-response relationships necessary for
      establishing control levels. Methacholine or histamine challenge testing for the
      measurement of non-specific bronchial hyperresponsiveness (NSBH) in
      epidemiological settings is safe when carried out according to a standardised
      protocol. Measurement of NSBH, a useful tool in the clinical assessment of
      occupational asthma, has also been used in screening workers in surveys of
      workforces at risk for occupational asthma. Standardisation and quality control
      are the key to the success of using lung function testing in the field.

PMID- 10907767
TI  - Prevalence and severity of asthma in adolescents in France. Cross-sectional and
      retrospective analyses of a large population-based sample.
AB  - SETTING: Asthma is the most common chronic respiratory disease among adolescents;
      however, very little is known about asthma in this age group. OBJECTIVE: To
      explore asthma in adolescence using cross-sectional and retrospective
      representative data. DESIGN: A population-based sample of adolescents was
      selected from 578 classes in 186 schools of eight metropolitan educational
      districts in France and invited to complete a self-administered questionnaire
      (National Adolescent Health Survey [NAHS]). RESULTS: Of 14,278 adolescents
      selected, 12,466 (87%) participated in the survey. Prevalence of 'ever asthma'
      was higher among boys, among those in the south and west, among those from French
      overseas departments, in active smokers, and in those with other allergies,
      including food allergy. It was lower in adolescents whose mother was a housewife.
      Puberty was not associated with 'ever asthma'; however, asthmatic boys without
      signs of puberty usually had more attacks than those with. Severe asthma was
      associated with early onset and female sex. Asthma medications and consultations
      did not depend on socio-economic status. Asthmatic adolescents were found to need
      more health care in terms of medication use, consultations and hospitalisations
      other than for asthma than other adolescents; this relationship was strongest
      among severe asthmatics.

PMID- 10907768
TI  - Work-related asthma: prevalence estimates by sex, age and smoking habits in a
      community sample.
AB  - SETTING: Two-phased study of a general population sample in Norway. OBJECTIVE: To
      assess the prevalence of work-related asthma by sex, age and smoking habits.
      DESIGN: The first phase, a mail questionnaire on asthma to a random sample of the
      general population of Hordaland County, Norway, gave a 90% response. A stratified
      sample of the responders (n = 1512) was invited to complete an occupational
      history questionnaire and performing spirometry and bronchial
      hyperresponsiveness. The attendance rate was 84%. Asthmatics were defined as
      having work-related asthma if they answered positively the questions: "Have you
      ever had respiratory symptoms in relation to your work? Did the symptoms improve
      on absence from work?" RESULTS: The prevalence of work-related asthma was 0.9% in
      this population, constituting 28% of all asthmatics (95% confidence interval 25
      31). The prevalence of work-related asthma was twice as high in men as in women,
      and did not differ significantly with age or between smoking groups. CONCLUSION:
      Work-related asthma amounts to a significant proportion of total asthma in this
      population. This should be taken into account by health planners as it is by
      definition a preventable disorder.

PMID- 10907769
TI  - Tuberculosis control in Sudan against seemingly insurmountable odds.
AB  - SETTING: Sudan, Africa's largest and one of its poorest countries, in which civil
      disturbance, resource limitation and communications difficulties are substantial
      impediments to delivery of health services. OBJECTIVES: To 1) illustrate the
      burden of tuberculosis; 2) review measures taken to control the disease; 3)
      outline the introduction of the DOTS strategy; and 4) demonstrate the trend in
      the output of the DOTS strategy. METHODS: Published information on general
      health, tuberculosis and health structure provide the setting. Routine reports
      illustrate the trend in case notification in Sudan, and outcome of treatment by
      period of enrollment on treatment (cohort). RESULTS: Since 1992, sputum smear
      microscopy centres have been established in existing health facilities (179 of a
      total 290 targeted centres). By the end of the second quarter of 1998, 82,860
      cases of tuberculosis had been reported, of whom 52% were sputum smear-positive
      cases. Of these, 89% had no history of previous treatment for as much as one
      month. The treatment outcomes for 11,000 new smear-positive cases were reported
      by the end of the second quarter of 1997; the proportion of notified cases for
      whom treatment results were available increased from 16% in 1994 to 63% in 1996.
      Of these, 72% were successfully treated, increasing from 62% in 1994 to 73% in
      1996. CONCLUSIONS: Despite seemingly overwhelming odds, the DOTS strategy has
      been successfully commenced and is in the process of expansion throughout the
      country, with monitoring of the quality of diagnostic examinations and
      improvements in treatment outcome. Further improvement is necessary, but appears
      feasible.

PMID- 10907770
TI  - Surveillance of Mycobacterium tuberculosis drug resistance in France, 1995-1997.
      AZAY Mycobacteria Study Group.
AB  - OBJECTIVE: To measure the rate of primary and secondary drug resistance of
      Mycobacterium tuberculosis on an ongoing basis. DESIGN: Data on all culture
      positive tuberculosis were collected prospectively from 1995 through 1997 from a
      microbiological laboratory network of 19 university hospitals throughout France,
      and submitted quarterly to the National Reference Centre for Surveillance of
      Mycobacterial Diseases. RESULTS: A total of 2998 patients were included in the
      study. Among the 2333 (78%) previously untreated patients, 8.6% had isolates
      resistant to any drug, 4.8% to streptomycin (SM) alone, 1.2% to isoniazid (INH)
      alone, 1.8% to SM + INH, and 0.3% to INH + rifampicin (RMP) or multidrug
      resistance (MDR). Foreign birth was independently associated with a higher risk
      of primary resistance to any drug (odds ratio [OR] 1.5). Among the 268 (9%)
      previously treated patients, 20.9% had isolates resistant to any drug, 6.3% to SM
      alone, 3.4% to INH alone, 4.1% to SM + INH, and 3.7% to INH + RMP. Foreign birth
      (OR = 2.3), and human immunodeficiency virus positive status (OR = 4.4) were
      independently associated with a higher risk of secondary resistance to any drug.
      CONCLUSION: During the last 30 years there has been no increase in resistance to
      any drug among previously untreated patients. As expected, secondary resistance
      was highly associated with foreign birth. MDR-TB remains a rare event in France.

PMID- 10907771
TI  - Clinical and programmatic mismanagement rather than community outbreak as the
      cause of chronic, drug-resistant tuberculosis in Buenaventura, Colombia, 1998.
AB  - SETTING: Buenaventura, Colombia. OBJECTIVE: To assess whether antituberculosis
      drug resistance was generated by poor management or community transmission.
      DESIGN: Treatment-failure and new tuberculosis (TB) patients identified between
      May 1997 and June 1998 were interviewed and their treatment histories reviewed.
      Bacteriologic testing, including drug susceptibility profiles (DSP) and DNA
      fingerprinting by restriction fragment length polymorphism (RFLP), was performed
      and human immunodeficiency virus (HIV) testing was offered. RESULTS: DSP and RFLP
      fingerprints were obtained for isolates from 34 of 64 treatment-failure patients;
      25 (74%) were resistant to > or = one drug. Fifteen of the 25 patients consented
      to HIV testing; none were positive. An average of 2.8 major treatment errors per
      patient was identified. RFLP from the treatment-failure patients revealed 20
      unique isolates and six clusters (isolates with identical RFLP); 4/6 clusters
      contained isolates with different DSP. Analysis of the RFLP from both treatment
      failure and new patients revealed that 44/111 (40%) isolates formed 18 clusters.
      Four of 47 (9%) new patients had multidrug-resistant TB (MDR-TB). Eleven isolates
      belonged to the Beijing family, related to the MDR strain W. CONCLUSION: Drug
      resistance in Buenaventura results from both poor management and community
      transmission. Dependence on DSP to identify TB transmission is inadequate when
      programmatic mismanagement is common.

PMID- 10907772
TI  - Improved sputum microscopy for a more sensitive diagnosis of pulmonary
      tuberculosis.
AB  - Diagnosis of tuberculosis in low-income countries is hindered by the low
      sensitivity of direct sputum smear microscopy. We compared an improved method
      based on liquefaction of sputum with NaOCl followed by centrifugation with
      standard direct smear in a central hospital and at peripheral health centres in
      Honduras. Specificity was high and sensitivity significantly better with the
      NaOCl method. Moreover, this technique is safe, inexpensive and easy to perform.
      We recommend its implementation to enable rapid, sensitive laboratory diagnosis
      of pulmonary tuberculosis, especially in resource-poor settings where culture is
      not possible.

PMID- 10907773
TI  - A prospective study of positive tuberculin reactions in women with or at risk for
      HIV-1 infection. HER Study Group. HIV Epidemiology Research.
AB  - We prospectively studied 1310 women with or at risk for HIV-1 infection to assess
      subsequent tuberculin reactions in those with > or = 10 mm induration. Forty
      seven HIV-positive and 57 negative women had tuberculin reactions > or = 10 mm
      induration; reversions to reactions < 10 mm occurred in 44% and 46% of those
      retested, respectively (P = NS). Among seropositives, reversions were associated
      with lower CD4+ lymphocyte count (P = 0.02). Of a total of 45 subsequent
      tuberculin tests in seropositive women, only two (4%) resulted in 5-9 mm
      induration, both at CD4+ counts < 500/mm3. Three (30%) of an additional 10
      seropositive women with maximal reactions of 5-9 mm induration reported prior
      tuberculosis exposure, a significantly lower proportion than the 36/47 (77%) with
      reactions > or = 10 mm induration (P < 0.01), but not different than women with
      maximal reaction sizes < 5 mm (219/814, 27%). This study suggests that reversions
      of > or = 10 mm tuberculin reactions to 5-9 mm are rare. In HIV-positive persons,
      especially those with CD4+ lymphocyte counts > or = 500/mm3, reaction sizes of 5
      9 mm often may not indicate Mycobacterium tuberculosis infection.

PMID- 10907774
TI  - The human heart rate response profiles to five vagal maneuvers.
AB  - Healthy teens and adults performed four vagotonic maneuvers. A large series of
      strabismus surgery patients had deliberately quantified tension on extraocular
      rectus muscles during general anesthesia. The mean bradycardia was greatest for
      diving response (apneic facial exposure to cold) and Valsalva maneuver and least
      for pressure on the globe and carotid sinus massage. Bradycardia occurred for
      every subject for the non-surgical maneuvers, however, extraocular muscle tension
      frequently caused no change in heart rate or even tachycardia. The inter-subject
      variance in percent heart rate change was greatest for surgical oculocardiac
      reflex. Of the rectus muscles, the inferior caused the most bradycardia while the
      lateral caused the least. The percent oculocardiac reflex was not age dependent.
      Occasional patients demonstrated profound bradycardia with strabismus surgery. Of
      these maneuvers, diving response has theoretical advantage in treating paroxysmal
      atrial tachycardia. The human cardiac vagal efferent was stimulated by several
      carefully controlled maneuvers resulting in wide inter-maneuver differences in
      bradycardia magnitude. The greatest intra-maneuver variability occurred with
      surgical oculocardiac reflex.

PMID- 10907776
TI  - Evaluating a new graphical ordinal logit method (GOLDminer) in the diagnosis of
      myocardial infarction utilizing clinical features and laboratory data.
AB  - OBJECTIVE: We used a new graphical ordinal logit method (GOLDminer) to assess a
      single cardiac troponin T (cTnT) analysis at the time of admission (first
      generation monoclonal; Roche BMC Corp., Indianapolis, Indiana), the character of
      chest pain, and electrocardiographic (ECG)findings in predicting the likelihood
      of acute myocardial infarction (AMI) in patients presenting with suspected
      myocardial ischemia. The final diagnosis of AMI was based on serial ECG findings
      and evolution of CKMB isoenzyme levels in conjunction with clinical findings.
      SUBJECTS: The study population consisted of 293 consecutive patients who
      presented at a mean of six hours after onset of chest pain or associated symptoms
      warranting a "rule-out" for AMI assessment to a university-affiliated community
      hospital. RESULTS: The odds-ratio for an elevated cTnT (> 0. 1 ng/ml) in AMI was
      22.2:1. There was an association between typical chest pain and cTnT (chi square
      = 78.23, p < .0001) and between abnormal ECG findings and cTnT (chi square = 108,
      p < .0001). The cTnT yielded diagnostic benefit in addition to chest pain
      characteristics and ECG findings in AMI. We present the odds-ratios for the
      combined features in GOLDminer plots. CONCLUSION: We demonstrate how the odds
      ratios for AMI are obtained after scaling continuous to ordinal the values for a
      single cTnT determination alone and with other features in patients presenting
      with chest pain.

PMID- 10907777
TI  - Abraham Flexner and the development of the Yale School of Medicine.
AB  - Abraham Flexner first toured the Yale University School of Medicine in
      preparation for his report of 1910, but it was just the beginning of his
      relationship with the school. While his review of Yale in his report was
      generally favorable, he mentioned several shortfalls that needed to be improved
      to make the school acceptable. Throughout the next twenty-five years, Flexner
      worked with Deans George Blumer and Milton C. Winternitz to improve the school's
      finances, infrastructure, and quality of education through his work with the
      Carnegie Foundation and General Education Board Flexner has been given great
      accolades for his work on medical education for the country, but little mention
      is made of him at Yale, even though he was one of the most influential figures in
      the development of Yale in the last century.

PMID- 10907775
TI  - Birth weight, maternal age, and education: new observations from Connecticut and
      Virginia.
AB  - It has been well established that increased maternal education, income, and
      social status contribute to increased birth weight, as well as reduced risk for
      low or very low birth weight offspring. However, there remains controversy about
      the mechanism(s) for this effect, as well as the interactions between these
      factors, maternal age, and race. Presented here is the analysis of a large,
      recent sample of over 20,000 consecutive live births in 12 hospitals, about half
      in Connecticut and half in Virginia, including a maternal population that is
      educationally and racially diverse. Although information on potentially relevant
      details such as prenatal care, smoking, occupation, and neighborhood is lacking
      the data set, there is sufficient information to explore the previously noted
      strong effect of maternal education on birth weight, as well as the large racial
      difference in outcome at every educational level after adjustment for the effects
      of age, marital status, state of residence, and gender of the offspring. However,
      this relationship was not monotonic, and there were differences in the effect
      between the white and black families, with black women showing a linear and
      consistent benefit from education across the range, while whites show a sharp
      benefit from completion of primary education, less from subsequent schooling. A
      surprising result was the apparent negative impact of very advanced education
      (>16 years), with lowered birth weights and higher risk of low birth weight
      offspring in the women with post-college training. The data also shed some
      addition light on the effect of age and birth weight. Whites show established
      improvement in birth outcome to about age 30, with slight decline thereafter,
      whereas in blacks there was progressive decline in birth weight with rising age
      starting in adolescence, as previously demonstrated by Geronimus. An additional
      unexpected observation was a sizable difference between births in Connecticut
      (larger, fewer low birth weight) than Virginia, correcting for all other
      covariates. It is hypothesized that this may reflect differences in services
      used, prenatal care in particular given similarities in smoking rates and other
      predictors. Because of the non-representativeness of and the limited information
      available in the present study, the conclusions should be taken as hypotheses for
      further research rather than definitive.

PMID- 10907778
TI  - Antifungal resistance in yeast vaginitis.
AB  - The increased number of vaginal yeast infections in the past few years has been a
      disturbing trend, and the scientific community has been searching for its
      etiology. Several theories have been put forth to explain the apparent increase.
      First, the recent widespread availability of low-dosage, azole-based over-the
      counter antifungal medications for vaginal yeast infections encourages women to
      self-diagnose and treat, and women may be misdiagnosing themselves. Their
      vaginitis may be caused by bacteria, parasites or may be a symptom of another
      underlying health condition. As a result, they may be unnecessarily and
      chronically expose themselves to antifungal medications and encourage fungal
      resistance. Second, medical technology has increased the life span of seriously
      immune compromised individuals, yet these individuals are frequently plagued by
      opportunistic fungal infections. Long-term and intense azole-based antifungal
      treatment has been linked to an increase in resistant Candida and non-Candida
      species. Thus, the future of limiting antifungal resistance lies in identifying
      the factors promoting resistance and implementing policies to prevent it.

PMID- 10907779
TI  - Intra-abdominal desmoplastic small round cell tumor.
AB  - BACKGROUND: Intra-abdominal desmoplastic small round cell tumor is a rare
      malignancy with a predilection for young males. Unique histological and
      immunocytochemical features distinguish the tumor from other members of the
      family of small round cell tumors of infancy and childhood. The aggressive nature
      of tumor spread, relative insensitivity to chemotherapy, and generally incomplete
      resectability result in a very poor prognosis. The authors report a case of a 39
      year-old man with diffuse abdominal and pelvic involvement of intra-abdominal
      desmoplastic small round cell tumor treated with aggressive chemotherapy and
      surgery. METHODS: Computed-tomography (CT)-guided biopsy of an omental mass was
      performed. Histologically, discrete nests of uniform closely packed malignant
      cells were distributed in a background of focally desmoplastic stroma.
      Immunocchemistry demonstrated positivity for epithelial, mesenchymal, and neural
      markers. On the basis of these unique histological and immunohistochemical
      characteristics, the diagnosis of desmoplastic small round cell tumor was made.
      The patient was treated with aggressive neoadjuvant chemotherapy consisting of a
      high-dose alkylator -based combination regimen, followed by surgery. RESULTS: The
      patient had a 10 to 15 percent regression in tumor mass in response to
      chemotherapy. Laparotomy revealed two large omental masses, another large mass
      adherent to the left colon and pelvic sidewall, and diaphragmatic, peritoneal and
      mesenteric studding with small nodules. Complete surgical resection was not
      possible. CONCLUSIONS: Intra-abdominal desmoplastic small round cell tumor
      remains an aggressive malignancy with an extremely poor prognosis. Although some
      response to chemotherapy may be possible, complete resection is rare, and
      surgical efforts are general palliative.

PMID- 10907780
TI  - Pancreatic adenocarcinoma presenting as sinistral portal hypertension: an unusual
      presentation of pancreatic cancer.
AB  - A rare syndrome, sinistral (left-sided) portal hypertension resulting from
      splenic vein thrombosis secondary to pancreatic adenocarcinoma of the tail is
      presented here. Pancreatic cancer is notorious for presenting with vague and
      nonspecific symptoms, including but not exclusively weight loss, abdominal pain,
      and anorexia with or without jaundice. However, physicians should be aware that
      in the presence of splenic vein thrombosis, this finding alone puts pancreatic
      cancer high on the differential diagnosis.

PMID- 10907781
TI  - Changes in fatty acid composition in plant tissues expressing a mammalian delta9
      desaturase.
AB  - Plant tissues expressing a mammalian stearoyl-CoA delta9 desaturase were reported
      to accumulate delta9 hexadecenoic acid (16:1), normally very minor in most plant
      tissues. The transgenic plants were thoroughly analyzed for alterations of
      individual lipids in different subcellular sites. Western blot analysis indicated
      that the animal desaturase was targeted to the microsomes. The delta9 16:1 was
      incorporated into both the sn-1 and sn-2 positions of all the major membrane
      lipids tested, indicating that the endoplasmic reticulum acyltransferases do not
      exclude unsaturated C16 fatty acids from the sn-2 position. In addition to
      increases in monounsaturated and decreases in saturated fatty acids, accumulation
      of 16:1 was accompanied by a reduction in 18:3 in all the lipids tested except
      phosphatidylglycerol, and increases in 18:2 in phospholipids. Total C16 fatty
      acid content in the galactolipids of the transgenics was significantly higher
      than that in the control, but those in the phospholipids were unchanged. In
      transgenics, delta11 18:1 was detected in the sn-1 position of the lipids tested
      except phosphatidylinositol and phosphatidylserine. Introduction of the animal
      desaturase, controlled by a seed-specific phaseolin promoter, into soybean
      somatic embryo resulted in a significant reduction in saturated fatty acids. Such
      effects were greater in cotyledons than hypocotyl-radicles. This study
      demonstrated that the animal desaturase can be used to decrease the levels of
      saturated fatty acids in a crop plant.

PMID- 10907782
TI  - Metabolism of 1-acyl-2-oleoyl-sn-glycero-3-phosphoethanolamine in castor oil
      biosynthesis.
AB  - We have examined the role of 2-oleoyl-PE (phosphatidylethanolamine) in the
      biosynthesis of triacylglycerols (TAG) by castor microsomes. In castor microsomal
      incubation, the label from 14C-oleate of 1-palmitoyl-2-[1-(14)C]oleoyl-sn-glycero
      3-phosphoethanolamine is incorporated into TAG containing ricinoleate. The enzyme
      characteristics, such as optimal pH, and the effect of incubation components of
      the oleoyl-12-hydroxylase using 2-oleoyl-PE as incubation substrate are similar
      to those for 2-oleoyl-PC (phosphatidylcholine). However, compared to 2-oleoyl-PC,
      2-oleoyl-PE is a less efficient incubation substrate of oleoyl-12-hydroxylase in
      castor microsomes. Unlike 2-oleoyl-PC, 2-oleoyl-PE is not hydroxylated to 2
      ricinoleoyl-PE by oleoyl-12-hydroxylase and is not desaturated to 2-linoleoyl-PE
      by oleoyl-12-desaturase. We have demonstrated the conversion of 2-oleoyl-PE to 2
      oleoyl-PC and vice versa. The incorporation of label from 2-[14C]oleoyl-PE into
      TAG occurs after its conversion to 2-oleoyl-PC, which can then be hydroxylated or
      desaturated. We detected neither PE-N-monomethyl nor PE-N,N-dimethyl, the
      intermediates from PE to PC by N-methylation. The conversion of 2-oleoyl-PE to 2
      oleoyl-PC likely occurs via hydrolysis to 1,2-diacyl-sn-glycerol by phospholipase
      C and then by cholinephosphotransferase. This conversion does not appear to play
      a key role in driving ricinoleate into TAG.

PMID- 10907784
TI  - Purification and biochemical characterization of a novel thermostable lipase from
      Aspergillus niger.
AB  - An extracellular 1,3-specific lipase with molecular weight of 35.5 kDa and an
      isoelectric point of 4.4 from Aspergillus niger has been purified 50-fold by pH
      precipitation followed by a series of chromatographic steps with an overall yield
      of 10%. The enzyme was homogeneous as judged by denaturing polyacrylamide gel
      electrophoresis and size-exclusion fast-performance liquid chromatography. It
      contained 2.8% sugar which was completely removed by endoglycosidase F treatment,
      and the deglycosylated enzyme retained full activity. The native lipase showed
      optimal activity between temperatures 35 and 55 degrees C and pH 5.0 and 6.0. The
      amino acid composition and the N-terminal sequence were found to be different
      from lipases previously purified from A. niger. The enzyme was resistant to
      trypsin, chymotrypsin, endoprotease Glu-C, thrombin, and papain under native
      conditions but was susceptible to cleavage by the same proteases when heat
      denatured.

PMID- 10907783
TI  - Purification of the acyl-CoA elongase complex from developing rapeseed and
      characterization of the 3-ketoacyl-CoA synthase and the 3-hydroxyacyl-CoA
      dehydratase.
AB  - Oleoyl-CoA elongase catalyzes four successive reactions: condensation of malonyl
      CoA to oleoyl-CoA, reduction, dehydration, and another reduction. Evidence
      supporting this mechanism and the multienzymatic nature of the elongation complex
      are reported. A particulate membrane fraction from rapeseed is able to elongate
      intermediates (R,S) 3-hydroxy-20:0-CoA and (E) 2,3-20:1-CoA to very long chain
      fatty acids in the presence of malonyl-CoA. Studies of the 3-ketoacyl-CoA
      synthase activities showed that maximal activity could be measured by using 15 to
      30 microM 18:1-CoA and 30 microM malonyl-CoA, and that 18:0-CoA and 18:1-CoA were
      the best substrates. Comparison of the condensation and the overall elongation
      activities indicated that condensation is the rate-limiting step of the
      elongation process. The 3-hydroxyacyl-CoA dehydratase activity was maximal in the
      presence of 75 microM Triton X-100 and 25 microg of proteins. Finally, the acyl
      CoA elongase complex was solubilized and purified. During the purification
      process, the 3-hydroxyacyl-CoA dehydratase copurified with the elongase complex,
      strongly suggesting that this enzyme belongs to the elongase complex. The
      apparent molecular mass of 700 kDa determined for the elongase complex, and the
      fact that four different polypeptide bands were detected after sodium dodecyl
      sulfate-polyacrylamide gel electrophoretic analysis of the purified fraction,
      further suggest that the acyl-CoA elongase is a multienzymatic complex.

PMID- 10907785
TI  - Effects of passive smoking on the regulation of rat aortic cholesteryl ester
      hydrolases by signal transduction.
AB  - The effects of exogenous oxidative stress due to passive smoking on cholesteryl
      ester (CE)-metabolizing enzymes and their regulatory kinases were examined by
      exposing rats to cigarette smoke (CS) for a 1-h period twice a day for 8, 12, or
      20 wk. An oxidatively modified low density lipoprotein (Ox-LDL) with a high lipid
      peroxide was identified in three CS groups after all three exposure periods. The
      rat aortic acid and neutral CE hydrolases (ACEH and NCEH) were activated to
      similar extents by both cAMP-dependent protein kinase (PKA) and protein kinase C
      (PKC) in the presence of their respective cofactors. The aortic PKC activity in
      the three CS groups exhibited significant reductions of 72, 84, and 75% as
      compared with the respective controls, which coincided with the reductions in the
      ACEH activities (86, 71, and 80%, respectively), whereas the PKA activities
      increased to 121, 197, and 252% in the three CS groups, respectively. Reflecting
      the increase of the PKA activity, the NCEH activity exhibited increases of 112%
      at 8 wk and 140% until 12 wk of exposure and decreased by 50% of the control
      value at 20 wk of exposure, suggesting inactivation of NCEH itself. The
      activation of acyl-CoA:cholesterol O-acyltransferase activity was associated with
      an increase of free cholesterol in aorta. The vitamin E diet prevented the
      formation of Ox-LDL and the oxidative inactivation of most enzymes, especially
      PKC, until 12 wk, but was less effective by 20 wk. The oxidative inactivation of
      PKC, particularly its activated form that translocated to the membrane fraction,
      was confirmed in the in vitro exposure to active oxygen generators at an optimal
      concentration; this inactivation was prevented by catalase and superoxide
      dismutase. These results suggested that the formation of Ox-LDL and alterations
      in CE-metabolizing enzymes caused by passive smoking could contribute to a
      twofold increase in the aortic CE content, thereby contributing to one of the
      mechanisms for atherosclerosis associated with smoking.

PMID- 10907787
TI  - Characterization of inositol phospholipids and identification of a mastoparan
      induced polyphosphoinositide response in Tetrahymena pyriformis.
AB  - The unicellular eukaryote Tetrahymena is a popular model for the study of lipid
      metabolism. Less attention, however, has been given to the inositol phospholipids
      of the cell, although it is known that this class of lipids plays an important
      role in eukaryotic cell signaling. Tetrahymena pyriformis phosphatidylinositol
      was isolated, purified, and characterized by proton nuclear magnetic resonance
      analysis and [2-(3)H]myoinositol labeling. Labeling was also used for
      polyphosphoinositide (phosphatidylinositol phosphate and phosphatidylinositol
      bisphosphate) identification. Tetrahymena inositol phospholipids were found to
      belong to the diacylglycerol group, although major Tetrahymena phospholipids,
      phosphatidylcholine and aminoethylphosphonoglycerides, have been found to be
      mainly alkylacylglyceroderivatives. Further characterization of Tetrahymena
      phosphatidylinositol by gas chromatographic analysis indicated that 80% of fatty
      acids were myristic acid and palmitic acid. This is also in contrast to the fatty
      acid profile of Tetrahymena phosphatidylcholine and phosphatidylethanolamine,
      with respect both to the fatty acid length and degree of unsaturation, and may
      indicate that specific diacylglycerol species are connected with the
      phosphatidylinositol metabolism in this cell. Treatment of [3H]inositol-labeled
      Tetrahymena cells with mastoparan, a G-protein-activating peptide, induced
      changes in the polyphosphoinositide levels, suggesting that inositol
      phospholipids may form in Tetrahymena a functional signaling system similar to
      that of higher eukaryotes. Addition of 10 microM mastoparan resulted in a rapid
      and transient increase in [3H]phosphatidylinositol phosphate followed by a
      decrease in [3H]phosphatidylinositol bisphosphate. Similar changes in lipids have
      been reported when phosphoinositide-phospholipase C pathway is activated in both
      animal and plant cells.

PMID- 10907786
TI  - Aggregation and fusion of vesicles composed of N-palmitoyl derivatives of
      membrane phospholipids.
AB  - N-Acylphosphatidylethanolamines and N-acylphosphatidylserines have been isolated
      from mammalian cells and have been associated with some tissue degenerative
      changes, although the relationship between their synthesis and the uncontrolled
      sequence of events that ends in irreversible tissue damage is not completely
      established. Our results show that monovalent and divalent cations induce
      aggregation and fusion of liposomes constituted by N
      palmitoylphosphatidylethanolamine (NPPE) and N-palmitoylphosphatidylserine
      (NPPS). The effectiveness of cations to induce the aggregation of NPPE and NPPS
      liposomes is Ca2+ > Mg2+ >> Na+. NPPS liposomes aggregate at lower concentrations
      of divalent cations than NPPE liposomes, but with sodium NPPE liposomes aggregate
      to a higher extent than NPPS liposomes. The reaction order for the aggregation
      processes depends on the lipid and the cation nature and range from 1.04 to 1.64.
      Dynamic light scattering shows an irreversible increase of the size of the
      aggregates in the presence of all cations tested. The irreversibility of the
      aggregation process and the intermixing of bilayer lipids, as studied by
      resonance energy transfer assay, suggest that fusion, rather than aggregation,
      occurs. The existence of a real fusion was demonstrated by the coalescence of the
      aqueous contents of both NPPS and NPPE liposomes in the presence of either
      monovalent or divalent cations. The different binding sensitivity of Ca2+ to NPPS
      and NPPE liposomes, determined by zeta potential measurements, agrees with the
      results obtained in the aggregation and fusion assays. Our results suggest that
      the synthesis in vivo of N-acylated phospholipids can introduce important changes
      in membrane-mediated processes.

PMID- 10907788
TI  - Molecular analysis of intact preen waxes of Calidris canutus (Aves: Scolopacidae)
      by gas chromatography/mass spectrometry.
AB  - The intact preen wax esters of the red knot Calidris canutus were studied with
      gas chromatography/mass spectrometry (GC/MS) and GC/MS/MS. In this latter
      technique, transitions from the molecular ion to fragment ions representing the
      fatty acid moiety of the wax esters were measured, providing additional
      resolution to the analysis of wax esters. The C21-C32 wax esters are composed of
      complex mixtures of hundreds of individual isomers. The odd carbon-numbered wax
      esters are predominantly composed of even carbon-numbered n-alcohols (C14, C16,
      and C18) esterified predominantly with odd carbon-numbered 2-methyl fatty acids
      (C7, C9, C11, and C13), resulting in relatively simple distributions. The even
      carbon-numbered wax esters show a far more complex distribution due to a number
      of factors: (i) Their n-alcohol moieties are not dominated by even carbon
      numbered n-alcohols esterified with odd carbon-numbered 2-methyl fatty acids, but
      odd and even carbon-numbered n-alcohols participate in approximately equal
      amounts; (ii) odd carbon-numbered methyl-branched alcohols participate abundantly
      in these wax ester clusters; and (iii) with increasing molecular weight, various
      isomers of the 2,6-, 2,8-, and 2,10-dimethyl branched fatty acids also
      participate in the even carbon-numbered wax esters. The data demonstrate that
      there is a clear biosynthetic control on the wax ester composition although the
      reasons for the complex chemistry of the waxes are not yet understood.

PMID- 10907789
TI  - Polyunsaturated monoglycerides and a pregnadiene in defensive glands of the water
      beetle Agabus affinis.
AB  - In addition to the C21 steroid 15alpha-hydroxypregna-4,6-dien-3,20-dione, four 1-
      or 2-acylated polyunsaturated monoglycerides, 1- or 2-(cis-5,8,11,14
      eicosatetraenoyl)-glycerol and 1- or 2-(cis-5,8,11,14,17
      eicosapentaenoyl)glycerol were identified as constituents of the prothoracic
      defensive gland secretion of the dytiscid beetle Agabus affinis by gas
      chromatography-mass spectrometry of trimethylsilylated gland extracts. In a
      feeding assay with minnows, synthetic samples of the two 2-acylated
      monoglycerides showed only a weak activity as a feeding deterrent. For that
      reason, other possible functions of the monoglycerides are discussed, such as
      roles as emulsifiers of cannabimimetics.

PMID- 10907790
TI  - Lipids of gelatinous Antarctic zooplankton: Cnidaria and Ctenophora.
AB  - Cnidaria (Calycopsis borchgrevinki, Diphyes antarctica, Stygiomedusa gigantea,
      Atolla wyvillei, Dimophyes arctica) and Ctenophora (Beroe cucumis, B. forskalii,
      Pleurobrachia pileus, Bolinopsis infundibulum) were collected near Elephant
      Island, South Shetland Islands, during January and February 1997 and 1998. Total
      lipid was low in all zooplankton (0.1-5 mg g wet mass) and included primarily
      polar lipids (59-96% of total lipid). Triacylglycerols were 0-26% of total
      lipids, and wax esters were 0-11% in all species. Cholesterol was the major
      sterol in all Cnidaria (50-63% of total sterols) whereas in most ctenophores it
      was lower at 26-45%. These cholesterol levels are consistent with a combined
      carnivorous and phytoplanktivorous diet in the ctenophores, with the carnivorous
      diet more dominant in the Cnidaria. Other sterols included primarily trans
      dehydrocholesterol, desmosterol, 24-methylcholest-5,22E-dien-3beta-ol, 24
      nordehydrocholesterol, and 24-methylenecholesterol. Total stanols were 0-6% in
      all zooplankton. Eicosapentaenoic acid and docosahexaenoic acid were the major
      polyunsaturated fatty acids (PUFA) in all samples (7-25% of total fatty acids)
      except for A. wyvillei in which docosapentaenoic acid was 10% of total fatty
      acids. The PUFA 18:5n-3 was not detected in 1997 samples, but constituted 0.2
      0.8% in most 1998 samples. Monounsaturated fatty acids included primarily 18:1n
      9c, 16:1n-7c, and 18:1n-7c. The principal saturated fatty acids in all samples
      were 16:0, 18:0, and 14:0. These data are the first for many of these zooplankton
      species and the first sterol data for most species. The use of the signature
      lipid approach has enabled examination of aspects of trophodynamics not
      obtainable by conventional techniques.

PMID- 10907792
TI  - Blood fatty acid composition of pregnant and nonpregnant Korean women: red cells
      may act as a reservoir of arachidonic acid and docosahexaenoic acid for
      utilization by the developing fetus.
AB  - Relative fatty acid composition of plasma and red blood cell (RBC) choline
      phosphoglycerides (CPG), and RBC ethanolamine phosphoglycerides (EPG) of pregnant
      (n = 40) and nonpregnant, nonlactating (n = 40), healthy Korean women was
      compared. The two groups were of the same ethnic origin and comparable in age and
      parity. Levels of arachidonic (AA) and docosahexaenoic (DHA) acids were lower (P
      < 0.05) and palmitic and oleic acids higher (P < 0.0001) in plasma CPG of the
      pregnant women. Similarly, the RBC CPG and EPG of the pregnant women had lower AA
      and DHA (P < 0.05) and higher palmitic and oleic acids (P < 0.01). The reduction
      in DHA and total n-3 fatty acids in plasma CPG of the pregnant women was
      paralleled by an increase in docosatetraenoic (DTA) and docosapentaenoic (DPA)
      acids of the n-6 series and in DPA/DTA ratio. In the RBC phospholipids (CPG and
      EPG) of the pregnant women, DTA and DPA acids of the n-6 series and DPA/DTA ratio
      did not increase with the decrease of the n-3 metabolites (eicosapentaenoic acid,
      DPA, and DHA) and total n-3. Since pregnancy was the main identifiable variable
      between the two groups, the lower levels of AA and DHA in RBC CPG and EPG of the
      pregnant women suggest that the mothers were mobilizing membrane AA and DHA to
      meet the high fetal requirement for these nutrients. It may also suggest that RBC
      play a role as a potential store of AA and DHA and as a vehicle for the transport
      of these fatty acids from maternal circulation to the placenta to be utilized by
      the developing fetus.

PMID- 10907793
TI  - Simultaneous derivatization of acyl and S-alkyl moieties of acyl thioesters by
      using trimethylsulfonium hydroxide for gas chromatographic analysis.
AB  - The reaction of long-chain acyl thioesters, viz. lauric acid dodecyl thioester,
      1,8-di-S-palmitoyl octanedithiol, and tristearoyl alpha-monothioglycerol, with
      trimethylsulfonium hydroxide in the presence of methanol leads to simultaneous
      derivatization of acyl moieties and S-alkyl moieties of acyl thioesters to the
      corresponding fatty acid methyl esters and methyl alkylsulfides, respectively.
      These derivatized products were analyzed by gas chromatographic technique.

PMID- 10907791
TI  - Trans fatty acids in adipose tissue of French women in relation to their dietary
      sources.
AB  - This study reports the fatty acid composition of subcutaneous adipose tissue in
      French women with special emphasis on the content of trans fatty acids
      originating from two main dietary sources, ruminant fats and partially
      hydrogenated vegetable oils (PHVO). Adipose tissue trans fatty acid levels from
      71 women, recruited between 1997 and 1998, were determined using a combination of
      capillary gas chromatography and silver nitrate thin-layer chromatography.
      Results indicate that on average cis monounsaturates accounted for 47.9% of total
      fatty acids, saturates for 32.2%, and linoleic acid for 14.4%. Cis n-3
      polyunsaturates represented only 0.7%. Total content of trans fatty acids was
      2.32 +/- 0.50%, consisting of trans 18:1 (1.97 +/- 0.49%), trans 18:2 (0.28 +/-
      0.08%), and trans 16:1 (0.06 +/- 0.03%). Trans 18:3 isomers were not detectable.
      The level of trans fatty acids found in adipose tissue of French women was lower
      than those reported for Canada, the United States, and Northern European
      countries but higher than that determined in Spain. Therefore, trans fatty acid
      consumption in France appears to be intermediate between that of the United
      States or North Europe and that of Spain. Based on the equation of Enig et al.,
      we estimated the mean daily trans 18:1 acid intake of French women at 1.9 g per
      person. The major trans 18:1 isomer in adipose tissue was delta11 trans, as in
      ruminant fats. Estimates of relative contribution of trans fatty acid intake were
      55% from ruminant fats and 45% from PHVO. This pattern contrasts sharply with
      those established for Canada and the United States where PHVO is reported to be
      the major dietary source of trans fatty acids.

PMID- 10907794
TI  - Reinvestigation of positional distribution of fatty acids in docosahexaenoic acid
      rich fish oil triacyl-sn-glycerols.
AB  - Positional distribution of fatty acids in triacyl-sn-glycerols of docosahexaenoic
      acid (DHA)-rich tuna orbital and bonito head oils has been reanalyzed by a method
      based on chromatographic separation of isomeric and enantiomeric monoacyl-sn
      glycerol (MAG) derivatives. When boric acid thin-layer chromatography (TLC) was
      used for separation of 1(3)- and 2-MAG analytical intermediates, the
      stereospecific analysis showed the preferential association of DHA to the sn-2
      position followed by the sn-3 position. This distribution pattern differed from
      that obtained by silicic acid TLC of their bis-3,5-dinitrophenylurethane (DNPU)
      derivatives. Reversed-phase high-performance liquid chromatography elution
      profiles of 1(3)- and 2-MAG intermediates revealed that 1(3)- and 2-MAG made up
      of both short- and long-chain lengths cannot be clearly resolved by TLC after
      preparation of the DNPU derivatives. The 1(3)- and 2-MAG must be resolved by
      boric acid TLC prior to derivatization.

PMID- 10907795
TI  - Understanding and influencing starch biochemistry.
AB  - Starch is one of the most important products synthesized by plants that is used
      in industrial processes. If it were possible to increase production or modify
      starches in vivo, using combinations or either genetically altered or mutant
      plants, it may make them cheaper for use by industry, or open up new markets for
      the modified starches. The conversion of sucrose to starch in storage organs is,
      therefore, discussed. In particular the roles of the different enzymes directly
      involved in synthesizing the starch molecules on altering starch structure are
      reviewed, as well as the different models for the production of the fine
      structure of amylopectin. In addition, the process of starch phosphorylation,
      which is also important in determining the physical properties of starches, is
      reviewed. It is hoped that detailed knowledge of these processes will lead to the
      rational design of tailored starches. Starch degradation is also an important
      process, for example, in the cold-sweetening of potato tubers, but outside of
      cereal endosperm little is known about the processes involved. The enzymes
      thought to be involved and the evidence for this are discussed.

PMID- 10907796
TI  - Dual role of plasma membrane electron transport systems in defense.
AB  - Because oxidative stress is one of the main sources of severe cellular damage,
      cells have different defense weapons against reactive oxygen species. Ubiquitous
      plasma membrane redox systems play a role in defense against oxidative stress
      damage. On the other hand, a tightly controlled and localized production of
      reactive oxygen species by a plasma membrane NADPH oxidase can be used as a
      potent microbicidal weapon. This dual, prooxidant and antioxidant role of plasma
      membrane electron transport systems in defense is studied and discussed.

PMID- 10907797
TI  - Structural and functional comparison of polysaccharide-degrading enzymes.
AB  - Sugar molecules as well as enzymes degrading them are ubiquitously present in
      physiological systems, especially for vertebrates. Polysaccharides have at least
      two aspects to their function, one due to their mechanical properties and the
      second one involves multiple regulatory processes or interactions between
      molecules, cells, or extracellular space. Various bacteria exert exogenous
      pressures on their host organism to diversity glycans and their structures in
      order for the host organism to evade the destructive function of such microbes.
      Many bacterial organism produce glycan-degrading enzymes in order to facilitate
      their invasion of host tissues. Such polysaccharide degrading enzymes utilize
      mainly two modes of polysaccharide-degradation, a hydrolysis and a beta
      elimination process. The three-dimensional structures of several of these enzymes
      have been elucidated recently using X-ray crystallography. There are many common
      structural motifs among these enzymes, mainly the presence of an elongated cleft
      transversing these molecules which functions as a polysaccharide substrate
      binding site as well as the catalytic site for these enzymes. The detailed
      structural information obtained about these enzymes allowed formulation of
      proposed mechanisms of their action. The polysaccharide lyases utilize a proton
      acceptance and donation mechanism (PAD), whereas polysaccharide hydrolases use a
      direct double displacement (DD) mechanism to degrade their substrates.

PMID- 10907798
TI  - The physician psychiatrist: 2000 and beyond.

PMID- 10907799
TI  - Thyroid function screening in acute geropsychiatric admissions.
AB  - Thyroid function abnormalities have been associated with psychiatric illness.
      Even though it is a common practice to assess thyroid function in geropsychiatric
      patients, a literature search for the past 10 years did not reveal any published
      studies of assessments of thyroid function abnormalities in acute geropsychiatric
      populations. A retrospective chart review of 197 acute geropsychiatric inpatients
      and 14 comparison group patients showed that 40 geropsychiatric patients and 2
      comparison group patients had abnormal thyroid function tests (TFfs). The most
      common abnormality was elevated triiodothyronine uptake (T3U), which was noted in
      19 female and 13 male geropsychiatric patients. The difference in the prevalence
      of TFT abnormalities between the geropsychiatric patients and the comparison
      group subjects was not statistically significant. Both T3U and free thyroxine
      index (FTI) were significantly higher in the female geropsychiatric patients than
      in the female comparison group patients. The abnormalities in T3U and FTI in this
      study group may be related to an increased prevalence of unidentified systemic
      illness or to the presence of chronically poor nutrition.

PMID- 10907800
TI  - Catatonia in a psychiatric intensive care facility: incidence and response to
      benzodiazepines.
AB  - This study was performed to establish the incidence of catatonia in a psychiatric
      intensive care unit, to test the Bush-Francis Catatonia Screening Instrument
      (BFCSI) and to assess the response of catatonic signs to benzodiazepines. During
      a 12-month period all patients admitted to a psychiatric intensive care unit were
      screened for catatonic signs using the BFCSI. Patients with catatonia were
      further assessed with the Bush-Francis Catatonia Rating Scale (BFCRS), the
      Modified Rogers Scale (MRS), and scales for associated psychotic and parkinsonian
      symptoms. They were treated with oral lorazepam or parenteral clonazepam and
      their responses evaluated daily. Neuroleptics were stopped for at least 3 days.
      Twenty four patients met the DSM IV criteria for catatonia, giving an incidence
      of 15% with a significantly higher proportion of non-Europeans. The most common
      associated diagnosis was schizophrenia (54%). Twenty two patients completed the
      benzodiazepine trial. All showed significant responses after 3 days of treatment.
      Sixteen (16/22, 73%) had full remission within 6 days, most within 2 to 4 days.
      Partial responders (n = 6) all had schizophrenia and were more likely to have
      longer pre-trial catatonic episodes. We find the BFCSI a simple and reliable tool
      to screen for catatonia, and our data attest to the efficacy of benzodiazepines
      in the treatment of catatonia.

PMID- 10907802
TI  - Lack of efficacy for fluoxetine in PTSD: a placebo controlled trial in combat
      veterans.
AB  - BACKGROUND: Fluoxetine and placebo were studied in a population of combat
      veterans with severe, chronic PTSD. METHODS: Twelve male veterans with PTSD were
      enrolled in a 12 week double-blind evaluation of fluoxetine and placebo. Mean
      fluoxetine dose at endpoint (week 12) was 48 mg/day with a range of 10 mg to 60
      mg. RESULTS: One fluoxetine patient responded (17%) and two of the six placebo
      patients responded (33%). CONCLUSIONS: Fluoxetine patients did not show a greater
      response than placebo patients in this small sample of male combat veterans with
      severe, chronic PTSD. Fluoxetine has displayed an efficacious response in
      controlled studies of patients with PTSD who were predominantly female, suffered
      civilian (noncombat) traumas, and were overall experiencing less severe PTSD. The
      reasons for the low response rate to fluoxetine in our study is unknown and will
      await further study examining variables other than symptoms that might influence
      outcome, such as gender, comorbidity, prior treatment history, trauma type,
      severity and chronicity.

PMID- 10907801
TI  - Nefazodone treatment of adolescent depression: an open-label study of response
      and biochemistry.
AB  - OBJECTIVE: The purpose of this study was to find whether nefazodone, effective in
      adult depression, might be similarly improve symptoms of adolescent depression.
      Secondary purpose was to relate platelet serotonin content to response, and to
      find if nefazodone's effect on platelet content was similar to that of the SSRIs.
      METHOD: 10 adolescents meeting DSMIV criteria for major depression received up to
      400 mg of nefazodone for an eight week period. Response was assessed at baseline,
      1, 2, 4, and 8 weeks by BDI and HDRS; platelet serotonin (5HT) content was
      obtained at baseline and final visit (for two dropouts, this was done at last
      visit, i.e., week 4). RESULTS: In LOCF analysis, significant improvement was
      found in both HDRS (20.9 to 8.9, p = .01) and BDI (24.6 to 10.2, p = .01). Eight
      of nine patients with available data showed increases in platelet 5HT content
      (.02). In seven patients of eight completers with available data, there was a
      nonsignificant trend for patients with platelet 5HT baseline greater than 30
      ng/10(8) platelets to show a greater change in HDRS than those with a baseline of
      less than 30 ng/10(8) platelets (p = .07). CONCLUSIONS: Further double-blind
      study of nefazodone in adolescent depression is indicated; nefazodone appears to
      increase platelet 5HT content.

PMID- 10907803
TI  - Neuroleptic malignant syndrome associated with amoxapine and lithium in an older
      adult.
AB  - This report describes the presentation of neuroleptic malignant syndrome (NMS) in
      the primary care setting in an older adult with major depression with psychosis.
      This patient had been stable on a regimen of amoxapine, lithium carbonate,
      lorazepam, and benztropine. The patient had rigidity, altered sensorium,
      diaphoresis, autonomic instability, elevated WBC count and urine myoglobin, and
      creatine phosphokinase (CPK) reaching 1331 U/I. He was successfully treated with
      bromocriptine.

PMID- 10907804
TI  - Mucinous metaplasias of the endometrium: biologically meaningful subsets for the
      practicing surgical pathologist.

PMID- 10907805
TI  - Mediastinal large B-cell lymphoma: new evidence in support of its distinctive
      identity.

PMID- 10907806
TI  - Colonic epithelial lymphocytosis and lymphocytic colitis: descriptive
      histopathology versus distinct clinicopathologic entities.

PMID- 10907807
TI  - Placental pathology for the surgical pathologist.
AB  - Pathologic examination of the placenta is of clinical importance in the
      evaluation of pregnancies with a less than perfect outcome. Morphologic
      alterations of the placenta can mirror disorders of the fetus and the mother and
      evaluation of the placenta can identify clinically significant lesions, allow
      understanding of a child's disability and may have a role in resolving medical
      legal disputes. Pathologic findings in the placenta can provide information on
      the pathogenesis of cerebral palsy, mental retardation, or neurodevelopmental
      disorders. This review will cover a variety of frequently encountered, clinically
      important, and morphologically distinct disorders of the placenta. The current
      understanding of the clinical implications of lesions for the mother, infant, and
      for future pregnancies will also be considered.

PMID- 10907808
TI  - Biopsy diagnosis of malignant versus benign liver "nodules": new helpful markers.
      An update.
AB  - Improved imaging techniques have led to an increased detection of suspicious
      "nodules" in the cirrhotic and noncirrhotic liver. Although the histologic
      diagnosis of clearly benign or clearly malignant lesions is usually
      straightforward, problems arise in the differential diagnosis of benign "nodules"
      and dysplastic lesions or well-differentiated hepatocellular carcinomas. This is
      especially so in limited diagnostic material, such as cytologic preparations from
      fine-needle aspirates and needle-core tissue biopsies. Recently, additional
      helpful markers have been described that may help to establish a conclusive
      diagnosis even on such material. Two of these, the reticulin stain and
      immunohistochemical staining for CD34, have been found to be useful also in
      cytologic cellblock material. Telomerase, a complex enzyme that is active in most
      malignant tumors, has also been found to show strong activity in most
      hepatocellular carcinomas. Mention is made of an immunohistochemical marker (MOC
      31), reported to be useful in the differentiation between metastatic
      adenocarcinoma and hepatocellular carcinoma.

PMID- 10907809
TI  - The Ljubljana classification: a practical strategy for the diagnosis of laryngeal
      precancerous lesions.
AB  - There is no internationally accepted classification of epithelial hyperplastic
      laryngeal lesions (EHLL). The majority of current classifications follow criteria
      similar to those commonly used for cervical epithelial lesions. However, the
      different etiology of laryngeal cancer and its particular clinical and histologic
      features necessitate a grading system more appropriate to this region. The
      Ljubljana classification of EHLL was devised in 1971 to cater to this
      requirement. Detailed criteria for histologic grading in this classification were
      formulated by a working group on EHLL of the European Society of Pathology in
      1999. The system recognizes four grades: simple and abnormal hyperplasia are
      benign categories; atypical hyperplasia ("risky" epithelium) is potentially
      malignant, and carcinoma in situ actually malignant. The main features by which
      the proposed grading system differs from other classifications are: 1. the
      distinction between benign and potentially malignant lesions; 2. the positive
      separation of carcinoma in situ from atypical hyperplasia; 3. the lack of
      prognostic significance for any surface keratin layer. The eventual outcome of
      EHLL patients so graded justifies the proposal for separating the lesions into a
      benign group, showing malignant transformation in only 0.9% of cases, from a
      potentially malignant group showing malignant transformation in 11% of cases. For
      diagnostically difficult cases, supplementary techniques such as those using
      morphometry, immunohistochemical and molecular biology are advised to improve the
      accuracy of diagnosis and predictions of their biological behavior.

PMID- 10907810
TI  - Silkiness in brown mink pelts characterized with optical methods.
AB  - In mink production, silkiness refers to a silky fur surface. The sensory
      evaluation of silkiness may be based on information perceived by the eyes and the
      hands. Silkiness is assumed to depend on hair fiber properties such as guard hair
      straightness, glossiness, and smoothness. Our objective was to characterize the
      dorsal surface of brown mink pelts by means of optical variables and relate these
      to the visual grades of silkiness, thereby forming some objective criteria of
      silkiness. Two groups of brown male mink pelts (winter coat) that originated from
      a selection trial with a focus on silkiness were used. The pelts came from a
      basic (Group 1992) population and a selected (Group 1994) generation. Group 1992
      was graded visually on a scale from 1 to 6 (most silky); Group 1994 was graded on
      a scale from 1 to 8 (most silky). With goniophotometric, nondestructive methods,
      the reflectance from each pelt surface was measured describing the angle
      dependent distribution of reflection in the shape of angular reflectance curves.
      The measurements were performed along (w-reflectance curve) and across (c
      reflectance curve) the guard hairs. The w-curve included a maximum assumed to be
      related to silkiness. Specular gloss, indicated by the maximum reflectance (s) in
      the direction of mirror reflection, was positively correlated with silkiness. For
      Group 1994, s = 72.94 + .49 x silkiness; r2 = .33, P = .0003. Correspondingly, an
      area representing specular (S) plus diffuse (D) reflectance (S + D) under the
      curve was positively correlated with silkiness. A decreasing band width of the w
      curve at 90% of maximum specular reflectance (w90) was related to an increase of
      silkiness (Group 1992: r = -.50, P < .01). Furthermore, both s/w90 and (S +
      D)/w90 were positively correlated with silkiness (Group 1992: r = .49, P < .01
      and r = .51, P < .01, respectively). Measures of contrast gloss involving
      relations or differences between specular and diffuse reflectance were not
      suitable. From our results, a high degree of specular gloss, indicated by s,
      explained and was related to an essential part of silkiness and general sensory
      quality of the pelts investigated. Also, s was relatively easy to measure. Thus,
      even if the objective variables did not correlate perfectly with visual
      judgments, s was considered to be the most usable objective variable in
      characterizing silkiness.

PMID- 10907811
TI  - Differences among Wagyu sires for USDA carcass traits and palatability attributes
      of cooked ribeye steaks.
AB  - The objective of this experiment was to evaluate the effects of various Wagyu
      sires on carcass quality traits and palatability attributes of cooked ribeye
      steaks. Wagyu sires were used and grouped as Old (n = 6) or New (n = 2) sires,
      based on the chronological order in which they were imported into the United
      States. One hundred thirteen F1 heifer and steer calves sired by Wagyu bulls out
      of three different sources of cows were fed a backgrounding diet for 112 d
      consisting of an 80:20 ratio of roughage:concentrate then grazed on a mixture of
      orchardgrass and bluegrass pasture for 84 d and finished on a 10:90 ratio of
      roughage:concentrate diet for 231 d in a feedlot. Progeny from New sires had
      larger (P < .05) ribeye areas, higher (P < .05) marbling scores, and lower (P <
      .05) maturity scores than progeny from Old sires. Marbling was positively
      correlated (P < .05) to brightness (r = .56), texture (r = .60), and fat luster
      (r = .38). Progeny of New sires had lower shear force values (P < .05) than
      progeny of Old sires. These results indicate the superiority of New Wagyu sires
      to produce progeny with more marbling, lower shear force values, and larger
      ribeye areas than Old Wagyu sires. Furthermore, there are substantial differences
      between Wagyu sires for carcass quality traits and palatability attributes.

PMID- 10907812
TI  - Effect of a trainer cow on health, behavior, and performance of newly weaned beef
      calves.
AB  - Experiments were conducted to investigate the effects of the presence of a
      trainer cow on behavior, performance, health, and feeding patterns of newly
      weaned beef calves. In Exp. 1,252 weaned calves (270+/-18 kg) were allocated to
      22 pens (11 to 15 calves per pen). A trainer cow was randomly assigned to each of
      11 pens. Calves were weighed prior to feeding on d 0, 3, 7, 14, 21, and 28.
      Rectal temperatures were taken on each of these days (except d 28) and blood
      samples were collected on d 0, 3, and 7 and subsequently analyzed for serum
      haptoglobin and leukotoxin antibody titers. Instantaneous scan observations of
      calf behavior were made at 10-min intervals between 0730 and 1730 on d 1, 2, 4,
      5, and 6. A similar protocol was used in Exp. 2, in which 297 calves (258+/-17
      kg) were allocated to 24 pens. Blood analyses included haptoglobin, white blood
      cell counts (WBC), and neutrophil:lymphocyte (NL) ratios. In Exp. 3, the above
      protocol was followed and patterns of feed bunk attendance of individual calves
      were also monitored using radio frequency identification by passive transponder
      ear tags. Trainer cows did not influence (P > .10) calf rectal temperatures,
      requirements for antibiotic therapy, WBC, NL ratios, or leukotoxin antibody
      titers. Pooled across treatments, NL ratios were lower (P < .01) on d 0 (.31)
      than on d 3 (.36) or d 7 (.39). Although differences in weight gain were detected
      in some periods within the three experiments, there were no differences (P > .10)
      overall (d 0 to 28). Trainer cows did not affect (P > .05) frequency or duration
      of bunk visits by the calves. Averaged across treatments, frequency and duration
      of bunk visits increased (P < .001) from 9.6 visits/d and 56.7 min/d between d 0
      and 3 to 12.3 visits/d and 108.9 min/d between d 15 and 21. The number of calves
      observed eating during scan sampling observations also increased from 16.4% on d
      1 to 25% on d 4 (P < .10) and 29% on d 5 and 6 (P < .05). More (P < .05) calves
      were observed lying on d 1 (41.7%) and d 2 (45.3%) than on d 4 (37.5%), d 5
      (34.8%), or d 6 (36.2%). With a trainer cow present, fewer (36.7% vs 41.5%; P <
      .001) calves were observed lying and more (11.7% vs 10.2%; P = .08) were observed
      walking than when no cow was present. Trainer cows did not improve calf health,
      time spent at the feed bunk, or performance of newly weaned calves.

PMID- 10907813
TI  - Evaluation of site and age of weaning on pig growth performance.
AB  - Site-segregated early weaning (SSEW) refers to the practice of weaning pigs from
      the sow at an early age and placing them in a nursery that is physically isolated
      from the breeding herd. An experiment involving 369 pigs was conducted at the
      Prairie Swine Center to investigate the impact of SSEW on pig performance when
      the herd of origin has a high health status and when housing and management
      conditions are kept as similar as possible across weaning regime. Three
      treatments were compared: weaning at 21+/-3 d and keeping the pigs on-site in an
      all-in-all-out nursery room (Control), weaning at 12+/-2 d of age and keeping the
      pigs on-site in a separate but identical all-in-all-out nursery room (OSEW), or
      weaning at 12+/-2 d of age and moving the pigs off-site to an all-in-all-out
      nursery room located 16 km from the Center (SSEW). Ventilation, feed, penning,
      feeders, and drinkers were kept as similar as possible for all treatments. Off
      site weaning improved 56-d body weight (P < .05) by 12.5 and 8.3% compared with
      OSEW and Control, respectively. The improvement appeared to be the result of
      improvements primarily in feed intake but also due to enhanced efficiency of
      nutrient utilization. This experiment confirms that SSEW results in significant
      improvements in 56-d weights, even when the herd of origin has a relatively high
      health status.

PMID- 10907814
TI  - Effect of subcutaneous vs intramuscular administration of P.G. 600 on estrual and
      ovulatory responses of prepubertal gilts.
AB  - The effects of s.c. and i.m. administration of P.G. 600 on estrual and ovulatory
      responses of prepubertal gilts were investigated. One hundred eighty-four
      crossbred gilts between 159 and 174 d of age were assigned to receive P.G. 600
      s.c. (s.c. P.G. 600) in the flank, P.G. 600 i.m. in the neck (i.m. P.G. 600), or
      no treatment (control). At the beginning of the study (d 0), animals were
      selected from a modified, open-front barn, regrouped, relocated to new pens, and
      exposed once daily to a mature boar to check for estrus. On d 17, ovaries were
      collected from all gilts and analyzed for the presence of corpora lutea (CL),
      cystic follicles, and cystic CL. A higher proportion of gilts expressed estrus
      with s.c. P.G. 600 (76%) than with i.m. P.G. 600 (52%, P < .01) or controls (15%,
      P < .01). The interval from initiation of treatment on d 0 to estrus was reduced
      (P < .01) by P.G. 600 (4.6 d) compared to controls (5.9 d), but there was no
      significant difference between P.G. 600 treatments. Both s.c. P.G. 600 (86%) and
      i.m. P.G. 600 (77%) induced more gilts to ovulate (P < .01) than controls (18%),
      but there was no significant difference between P.G. 600 treatments. No
      significant effect of treatment was detected on number of CL (17.9), number of
      cystic follicles (1.5), or number of cystic CL (2.1). Proportions of gilts that
      developed cystic follicles or cystic CL were not influenced by treatment. Results
      of this study indicated that s.c. administration of P.G. 600 significantly
      improved the induction of estrus in prepubertal gilts compared to i.m.
      administration.

PMID- 10907815
TI  - Influence of ruminal biohydrogenation on the feeding value of fat in finishing
      diets for feedlot cattle.
AB  - Four Holstein steers (212 kg) with cannulas in the rumen and proximal duodenum
      were used in a 4 x 4 Latin square experiment to study the influence of degree of
      ruminal biohydrogenation (BH) on the feeding value of supplemental fat.
      Treatments consisted of an 88% concentrate finishing diet supplemented with 1) 2%
      yellow grease (control); 2) 4% formaldehyde-protected fat (Rumentek), 2% yellow
      grease (LBH); 3) 2% Rumentek, 4% yellow grease (MBH); or 4) 6% yellow grease
      (HBH). Ruminal BH of HBH, MBH, and LBH diets was 74, 68, and 54%, respectively.
      High-fat supplementation decreased (7%, P < .05) intestinal digestibility of 18:0
      but increased intestinal digestibility of 18:1 (3%, P < .10), 18:2 (14%, P <
      .01), and 18:3 (23%, P < .05). Increases in intestinal digestibility of 18:0
      (quadratic effect, P < .05), 18:1 (linear effect, P < .01), 18:2 (linear effect,
      P < .01), 18:3 (linear effect, P < .05), and total fatty acids (linear effect, P
      < .05) were inversely related to BH. For every 1% increase in the proportion of
      18:1 fat entering the small intestine, the digestibility of 18:0 increased 1%.
      High-fat supplementation depressed ruminal digestion of OM (11%, P < .05), NDF
      (16%, P < .05), starch (6%, P < .05), and feed N (12%, P < .01). Formaldehyde
      protein protection of fat diminished its depressing effects on ruminal digestion
      of NDF (quadratic effect, P < .10) and enhanced ruminal escape of feed N (linear
      effect, P < .10). Postruminal digestion of OM was greater (4.6%, P < .10) for
      high-fat diets. High-fat diets decreased (P < .05) total tract digestion of OM
      (1.9%), NDF (7.4%), and starch (.5%). Postruminal and total tract digestibility
      of OM, NDF, N, and starch was not affected (P > .10) by BH. In a 125-d finishing
      trial, 100 yearling steers (362 kg) were used to evaluate treatment effects on
      growth performance. High-fat diets did not affect (P > .10) ADG but increased (P
      < .10) feed efficiency (9%, P < .10), dietary NEm (7.6%, P < .05), and dressing
      percentage (9%, P < .05). The magnitude of the increase in dressing percentage
      was inversely related (linear effect, P < .10) to BH. We conclude that decreasing
      ruminal BH will increase postruminal digestibility of fat, and hence the NE value
      of dietary fat. The synergistic effect of increasing the proportion of 18:1 on
      intestinal digestion of fat enables higher levels of fat supplementation.
      Protecting fat from BH minimizes the detrimental effects of supplemental fat on
      fiber digestion.

PMID- 10907816
TI  - Synchronizing estrus and(or) ovulation in beef cows after combinations of GnRH,
      norgestomet, and prostaglandin F2alpha with or without timed insemination.
AB  - Three experiments were conducted to induce estrus and(or) ovulation in 1,590
      suckled beef cows at the beginning of a spring breeding season. In Exp. 1, 890
      cows at three locations were allotted to three treatments: 1) GnRH on d -7 +
      prostaglandin F2alpha (PGF2alpha) on d 0 (Select Synch); 2) GnRH on d -7 +
      PGF2alpha on d 0 (first day of the breeding season) plus a norgestomet implant
      (NORG) between d -7 and 0 (Select Synch + NORG); or 3) two injections of
      PGF2alpha given 14 d apart (2xPGF2alpha). More (P < 0.05) cycling cows were
      detected to have been in estrus after both treatments that included GnRH,
      whereas, among noncycling cows, the addition of norgestomet further increased (P
      < 0.05) the proportion in estrus. Pregnancy rates were greater (P < 0.01) among
      noncycling cows after treatments that included GnRH. For cows that calved >60 d
      before the onset of the breeding season, conception rates were greater (P < 0.01)
      than those that calved < or =60 d regardless of treatment, whereas days
      postpartum had no effect on rates of detected estrus. When body condition scores
      were < or =4 compared with >4, rates of detected estrus (P < 0.05) and conception
      (P = 0.07) were increased. In Exp. 2, 164 cows were treated with the Select Synch
      + NORG treatment and were inseminated either after estrus or at 16 h after a
      second GnRH injection (given 48 h after PGF2alpha). Conception and pregnancy
      rates tended (P = 0.08) to be or were less (P < 0.05), respectively, for
      noncycling cows inseminated by appointment, but pregnancy rates exceeded 53% in
      both protocols. In Exp. 3, 536 cows at three locations were treated with the
      Select Synch protocol as in Exp. 1 and inseminated either: 1) after detected
      estrus (Select Synch); 2) at 54 h after PGF2alpha when a second GnRH injection
      also was administered (Cosynch); or 3) after detected estrus until 54 h, or in
      the absence of estrus, at 54 h plus a second GnRH injection (Select Synch +
      Cosynch). Conception rates were reduced (P < 0.01) in cows that were inseminated
      by appointment. An interaction of AI protocol and cycling status occurred (P =
      0.05) for pregnancy rates with differing results for cycling and noncycling cows.
      Across experiments, variable proportions of cows at various locations (21 to 78%)
      were cycling before the breeding season. With the GnRH or GnRH + NORG treatments,
      ovulation was induced in some noncycling cows. Conception rates were normal and
      pregnancy rates were greater than those after a PGF2alpha program, particularly
      when inseminations occurred after detected estrus.

PMID- 10907818
TI  - Interaction of protein nutrition and laidlomycin on feedlot growth performance
      and digestive function in Holstein steers.
AB  - Two isonitrogenous diets (12.5% CP) containing 20 (20% NPN) or 40% (40% NPN) of
      the N as nonprotein N were evaluated with 0 or 10 mg laidlomycin propionate
      (LP)/kg in a 2 x 2 factorial arrangement. Changes in dietary NPN:N ratio were
      developed by partial substitution of urea N for fish meal N. In Trial 1, four
      Holstein steers (349 kg) with cannulas in the rumen and proximal duodenum were
      used to evaluate treatment effects on digestive function. Total tract OM
      digestion was slightly greater (1.2%, P < .10) for diets containing 20% of N as
      NPN, due to greater (3.4%, P < .05) postruminal OM digestion. Supplemental LP
      decreased passage of microbial N to the small intestine (7.4%, P < .10) and
      ruminal degradation of dietary CP (DIP, 8.1%, P < .10). Decreasing the NPN:N
      ratio decreased microbial N flow to the small intestine (7.5%, P < .10) and DIP
      (15%, P < .01) and increased (6%; P < .05) the flow of indispensable amino acids
      to the small intestine. Supplemental LP increased (P < .10) ruminal pH. There
      were no treatment effects (P > .10) on ruminal molar proportions of acetate or
      propionate. In Trial 2, 120 Holstein steers (122 kg) were used to evaluate
      treatment effects on growth performance. Decreasing the NPN:N ratio increased ADG
      (P < .01) by 36, 40, and 16%, respectively, for the initial three 56-d periods of
      the trial. Overall, ADG was 17% greater (P < .01) for cattle consuming diets
      containing 20 vs 40% NPN. Decreasing the NPN:N ratio increased (P < .01) gain
      efficiency by 17 and 14%, respectively, for the initial two 56-d periods.
      Overall, gain efficiency was 6% greater (P < .01) for diets containing 20% NPN.
      Dietary NPN:N ratio did not influence (P > .10) the NE value of diets.
      Supplemental LP did not affect DMI (P > .10) but increased ADG (6%, P < .01) and
      gain efficiency (5%, P < .05) and decreased (11%, P < .05) the maintenance energy
      requirements. Protein nutrition limited growth performance of calves receiving
      the 20% NPN diets during the initial 112 d of the trial. With the 40% NPN diets,
      protein nutrition limited growth performance throughout most of the trial (d 1 to
      d 224). We conclude that LP will enhance daily weight gain and gain efficiency of
      calf-fed Holstein steers. Conventional urea-based diets will not diminish
      response to LP, although they may not meet the metabolizable amino acid
      requirements of calf-fed Holsteins during the first three-quarters of the feeding
      period.

PMID- 10907817
TI  - Effects of weaning age and diet on growth and carcass characteristics in steers.
AB  - Two experiments were conducted to determine the effects of diet on growth of
      steers weaned at approximately 100 vs 205 d of age. In Exp. 1, a 2 x 2 x 2
      factorial experiment was conducted using 78 Angus crossbred cow-calf pairs. The
      factors examined were age at weaning (early, at 103+/-3 d [EW] vs normal, at
      203+/-3 d [NW]), feeding strategy (ad libitum vs postweaning programmed intake),
      and dietary CP concentration (100 vs 120% of NRC [1984] recommended levels).
      Early-weaned calves had a greater (P < .001) ADG than NW calves from 103 to 203 d
      and reached market weight at 385 d vs 418 d for NW calves (P < .001). Likewise,
      steers offered feed for ad libitum consumption reached market weight at 394 d,
      compared with 409 d for programmed-intake steers (P < .05). In Exp. 2, 64 Angus
      crossbred steers were either weaned at 93+/-3 d and fed one of four diets, weaned
      at 210+/-3 d without access to creep feed, or weaned at 210+/-3 d with access to
      creep feed for 60 d prior to weaning. Early-weaned calves were heavier (P < .01)
      than NW calves at 210 d if fed either 100 or 90% concentrate diets, and they had
      greater (P < .001) backfat thickness at 210 d but no difference (P > .10) in
      longissimus muscle area compared to EW calves fed a 60% concentrate diet. At
      slaughter, 80 to 100% of steers on all treatments graded low Choice or higher.
      Feeding high-concentrate diets to EW beef calves accelerated growth rate and fat
      deposition early in the feeding period and may be a way to provide young cattle
      for a high-quality beef market.

PMID- 10907819
TI  - Palatability of wethers fed an 80% barley diet processed at different ages and of
      yearling wethers grazed on native range.
AB  - Seasonal availability of lamb in the Western United States contributes to a large
      fluctuation in lamb supply and value. However, alternatives to fall marketing may
      not be practical unless palatability traits are acceptable. A 3-yr study was
      conducted to investigate 1) the effects of slaughter age (7 to 8; 10 to 11; or 14
      to 15 mo) on carcass and palatability characteristics of wethers fed an 80%
      barley diet (Exp. 1); and 2) the effects of finishing on range or on an 80%
      barley diet on carcass and palatability traits of 14- to 15-mo-old wethers (Exp.
      2). In Exp. 1, no differences (P = .27) were detected in flavor intensity or
      longissimus muscle area among slaughter age groups, but fat depth was greater (P
      < .05) for 7- to 8-mo-old wethers than for 10- to 11- or 14- to 15-mo-old
      wethers. Year x slaughter age interactions were detected (P < .10) for hot
      carcass weight, Warner-Bratzler shear value, body wall thickness, and percentage
      kidney fat. Hot carcass weight was greater (P < .05) for 14- to 15-mo-old wethers
      than for both groups of younger wethers in yr 1, did not differ (P = .53) among
      slaughter ages in yr 2, and was greater (P < .05) for 10- to 11- than for 14- to
      15-mo-old wethers in yr 3. Warner-Bratzler shear values did not differ (P > .10)
      among slaughter ages in yr 1 and 3, but shear values for 14- to 15-mo-old wethers
      were greater (P < .05) than for both younger slaughter age groups in yr 2.
      Percentage kidney fat was lower (P < .05) for 14- to 15- than for 7- to 8-mo-old
      wethers in all years. In Exp. 2, flavor intensity of the meat did not differ (P =
      .35) between finishing systems, but longissimus muscle area was greater (P = .02)
      for range-finished wethers than for wethers fed an 80% barley diet. Year x
      finishing treatment interactions were detected (P < .10) for shear values, body
      wall thickness, percentage kidney fat, and fat depth. Shear values were greater
      (P = .10) for range-finished wethers than for wethers fed an 80% barley diet in
      yr 1, but did not differ (P > .55) in yr 2 and 3. Body wall and fat measurements
      were greater (P < .10) for wethers fed an 80% barley diet than for range-finished
      wethers in all years except yr 3, when fat depth did not differ (P = .47).
      Overall, slaughtering wethers fed an 80% barley diet or range-finished wethers at
      older ages produced acceptable carcasses with desirable meat palatability traits.

PMID- 10907820
TI  - Genetic analyses of live-animal ultrasound and abattoir carcass traits in
      Australian Angus and Hereford cattle.
AB  - In order to estimate genetic parameters, abattoir carcass data on 1,713 Angus and
      1,007 Hereford steers and heifers were combined with yearling live-animal
      ultrasound measurements on 8,196 Angus and 3,405 Hereford individuals from
      seedstock herds. Abattoir measures included carcass weight (CWT), percentage of
      retail beefyield (RBY), near-infrared measured intramuscular fat percentage
      (CIMF), preslaughter scanned eye muscle area (CEMA), and subcutaneous fat depth
      at the 12th rib (CRIB) and at the P8 site (CP8). Ultrasound scans on yearling
      animals included 12th-rib fat depth (SRIB), rump fat depth at the P8 site (SP8),
      eye muscle area (SEMA), and percentage of intramuscular fat (SIMF). Records on
      CWT were adjusted to 650-d slaughter age, and the remaining abattoir traits were
      adjusted to 300-kg CWT. Scan data were analyzed treating records on males and
      females as different traits. Multivariate analyses were performed on a variety of
      trait combinations using animal model and REML algorithm. Heritability (h2)
      estimates for CWT, RBY, CIMF, CP8, CRIB, and CEMA were .31, .68, .43, .44, .28,
      and .26, respectively, for Angus and .54, .36, .36, .08, .27, .38, respectively,
      for Hereford. Pooled across sexes, h2 estimates for SIMF, SP8, SRIB, and SEMA
      were .33, .55, .51, and .42, respectively, for Angus and .20, .31, .18, and .38,
      respectively, for Hereford. Genetic correlations (r(g)) between the same pair of
      carcass traits measured at yearling through scanning and directly at the abattoir
      were moderate to strongly positive, suggesting that selection using yearling
      ultrasound measurements of seedstock cattle should result in predictable genetic
      improvement for abattoir carcass characteristics. Estimates of r(g) between the
      scanned fat measurements and RBY were negative, ranging from -.85 for Angus
      heifers to -.05 for Hereford heifers. Also, the estimates of r(g) between SEMA
      and the fat records measured at the abattoir were negative and ranged from -.94
      in Hereford heifers to -.02 in Angus heifers.

PMID- 10907821
TI  - Accounting for lactation length and weaning-to-conception interval in genetic
      evaluations for litter size in swine.
AB  - Effects of lactation length and weaning-to-conception interval on the subsequent
      litter size of purebred sows were estimated using an animal model. Data on 2,847
      Landrace sows with 7,125 litters born between January 1989 and May 1997 and on
      1,234 Yorkshire sows with 2,999 litters born between January 1990 and May 1997
      were obtained from two Canadian selection herds. Sows having a lactation of less
      than 14 d (MMEW) were usually not mated until their second estrus, whereas sows
      weaned after at least 14 d of lactation (later weaning) were usually mated on
      their first estrus. Litter size included both number of pigs born alive and those
      stillborn. Linear, quadratic, and logarithmic effects of lactation length were
      tested. The effect of weaning-to-conception interval on litter size was modeled
      using an approach based on threshold variables and an approach using segmented
      polynomials. Results indicated linear and logarithmic effects of lactation length
      on subsequent litter size for Yorkshire and Landrace breeds, respectively. Litter
      size decreased as weaning-to-conception interval increased up to 7 and 10 d for
      Yorkshire and Landrace, respectively, then increased with further increases in
      weaning-to-conception interval up to 35 and 30 d for the two breeds, and then
      remained constant. The MMEW sows did not have lower subsequent litter sizes than
      later-weaned sows because the negative effect of a shorter lactation was offset
      by the positive effect of a longer weaning-to-conception interval. However,
      average time spent open per parity was longer for MMEW sows than for later-weaned
      sows. Both lactation length and weaning-to-conception interval should be
      considered in models for the genetic evaluation of litter size in purebred swine.
      Segmented polynomials can be used to predict litter size as a continuous function
      of weaning-to-conception interval or to derive weaning-to-conception interval
      adjustment factors for litter size.

PMID- 10907822
TI  - Frequency of the Rendement Napole RN- allele in a population of American
      Hampshire pigs.
AB  - A total of 204 purebred Hampshire pigs were obtained from 23 breeders. These
      animals were the progeny of 41 sires and 123 dams. A sample of purebred Yorkshire
      (n = 24) pigs were also used in the study. Animals were classified by glycolytic
      potential determined on a live-animal longissimus muscle biopsy sample. Hampshire
      pigs (n = 176) with glycolytic potential greater than 185 micromol/g (x = 238.8
      micromol/g; SD = 29.54) were classified as heterozygous or homozygous for the
      dominant RN- allele (RN-rn+ or RN-RN-, respectively), whereas cohorts (n = 28)
      with glycolytic potential less than 185 micromol/g (x = 141.3 micromol/g; SD =
      24.48) were considered as homozygous normal (rn+rn+). All Yorkshire pigs (n = 24)
      had a mean glycolytic potential level of 146.1 micromol/g (SD = 20.18) and were
      considered as homozygous normal (rn+rn+). The Hardy-Weinberg equilibrium yielded
      frequencies of .630 and .370 for the dominant RN- allele and normal rn+ alleles
      in the Hampshire population, respectively, and genotypic frequencies of .397 (RN
      RN-), .466 (RN-rn+), and .137 (rn+rn+). Hampshires with glycolytic potential > or
      = 185 micromol/g had significantly lower longissimus muscle ultimate pH,
      intramuscular fat, subjective marbling scores, and percentage of protein (P <
      .001) and had greater longissimus muscle percentage of moisture (P < .001), drip
      loss (P < .01), and cooking loss (P < .001) than rn+rn+ Hampshires and
      Yorkshires. These data suggest the RN- allele exists at a high frequency within
      the American Hampshire breed. Higher glycolytic potential levels, which accompany
      the allele, may cause decreased meat quality.

PMID- 10907823
TI  - A generalized Michaelis-Menten equation for the analysis of growth.
AB  - The functional form W = (W0Kc + Wf t(c)) /(Kc + t(c)), where W is body size at
      age t, W0 and Wf are the zero- and infinite-time values of W, respectively, and K
      and c are constants, is derived. This new generalized Michaelis-Menten-type
      equation provides a flexible model for animal growth capable of describing
      sigmoidal and diminishing returns behavior. The parameters of the nonlinear model
      are open to biological interpretation and can be used to calculate reliable
      estimates of growth traits, such as maximum or average postnatal growth rates. To
      evaluate the new model, the derived equation and standard growth functions such
      as the Gompertz and Richards were used to fit 83 growth data sets of different
      animal species (fish, mice, hamsters, rats, guinea pigs, rabbits, cats, dogs,
      broilers, turkeys, sheep, goats, pigs, horses, and cattle) with a large range in
      body size. A comparative study was carried out based on mathematical,
      statistical, and biological characteristics of the models. The statistical
      goodness-of-fit achieved with the new model was similar to that of Richards, and
      both were slightly superior to the Gompertz. The new model differed from the
      others with respect to some of the estimated growth traits, but there were highly
      significant correlation coefficients between estimates obtained with the
      different models, and the ranking of animals based on growth parameters computed
      with the new function agreed with the rankings computed by the other models.
      Therefore, the new model, with its variable inflection point, was able to
      adequately describe growth in a wide variety of animals, to fit a range of data
      showing sigmoidal growth patterns, and to provide satisfactory estimates of
      traits for quantifying the growth characteristics of each type of animal.

PMID- 10907824
TI  - Effects of graded levels of potato by-products in barley- and corn-based beef
      feedlot diets: I. Feedlot performance, carcass traits, meat composition, and
      appearance.
AB  - To measure effects of diet on feedlot performance, carcass characteristics, and
      beef appearance, 144 crossbred beef steers (333+/-.44 kg) were allotted within
      weight block (3) to a randomized complete block design with a 2 x 3 factorial
      arrangement of dietary treatments. Main effects were grain (barley or corn) and
      level of potato by-product (PB) (0, 10, or 20% of diet DM). Steers were fed diets
      containing 83% concentrate (grain plus PB), 10% supplement, and 7% alfalfa on a
      DM basis for an average of 130 d. Level of PB quadratically affected (P < .10) DM
      intake and gain such that steers fed 10% PB ate more and gained faster. Corn-fed
      steers were more (P < .05) efficient (5.8 vs 6.3 kg DM/kg gain) and had more (P <
      .05) kidney, pelvic, and heart fat (2.2 vs 2.0%) than barley-fed steers. A grain
      x PB interaction was detected (P < .10) for marbling score, which was minimized
      in steers fed barley diets (small 0) but maximized in those fed corn diets (small
      30) at 10% PB. Diet did not affect beef firmness or beef color score. Barley-fed
      beef had whiter fat (P < .05) than corn-fed beef (2.6 vs 2.9 on a 1 to 7 scale);
      however, fat luster score was not affected by diet. Small differences were noted
      in fatty acid profile, purge, drip loss, and muscle pH. No differences were noted
      in color measurements due to dietary treatment over 7 d of retail shelf life.
      Overall, differences were small and probably not biologically important. These
      results indicate that these diets had minimal effects on beef appearance and
      carcass characteristics, meat composition, and water retention properties.

PMID- 10907826
TI  - Effects of rate of pH fall, time of deboning, aging period, and their interaction
      on veal quality characteristics.
AB  - Three groups of veal carcasses were selected on the basis of their pH in the
      longissimus lumborum muscle at 3 h postmortem (pH3) to study the effects and
      interaction with time of deboning on quality characteristics of veal. The
      following groups of 10 calves each were selected: 1) fast pH fall, pH3 < 6.2; 2)
      intermediate pH fall, 6.2 < pH3 < 6.7; and 3) slow pH fall, pH3 > 6.7.
      Longissimus thoracis et lumborum (LTL) muscles of sides of the selected carcasses
      were randomly assigned to be excised at either 24 or 48 h postmortem. Color,
      water-holding capacity, and shear force measurements were determined after an
      aging period of 2, 3, 4, 7, and 14 d, respectively. Color of longissimus muscle
      samples from veal calves with similar preslaughter blood hemoglobin values
      becomes significantly lighter with a faster pH fall. Muscle color was not
      affected by time of deboning and overall color of all longissimus samples
      remained stable during storage and was not affected by rate of pH fall and time
      of deboning. Cooking losses increased with both a faster rate of pH fall and by
      deboning at 24 h postmortem. Drip losses during vacuum storage were higher for
      muscles excised at 24 rather than 48 h postmortem. Both when deboned at 24 and 48
      h, postmortem veal carcasses with a lower rate of pH fall had higher shear force
      (SF) values than did carcasses with a higher rate of pH fall. Deboning at 24 h
      postmortem resulted in higher SF values than deboning at 48 h postmortem.
      Differences in SF between 24- and 48-h deboning were larger in slower glycolyzing
      carcasses. Aging improved tenderness but did not fully reduce the difference in
      SF values between 24- and 48-h deboning. The results suggest that deboning of
      veal carcasses before the ultimate pH has been reached may result in muscle
      contraction, which may exert negative effects on tenderness and water-holding
      capacity of veal. Effects of time of deboning can, at least partly, be explained
      by differential effects on shortening of the muscle fibers.

PMID- 10907825
TI  - Effects of graded levels of potato by-products in barley- and corn-based beef
      feedlot diets: II. Palatability.
AB  - The objective of this study was to evaluate the effects of barley- or corn-based
      diets containing 0, 10, or 20% potato by-product (DM basis) on Warner-Bratzler
      shear force and palatability of beef. One hundred forty-four crossbred beef
      steers (333+/-.44 kg) were allotted within weight block (3) to a randomized
      complete block design with a 2 x 3 factorial arrangement of dietary treatments.
      Main effects were grain (barley or corn) and level of potato by-product (0, 10,
      or 20% of diet DM). There were a total of 18 pens with eight steers per pen and
      three pens per treatment. Steers were fed diets containing 83% concentrate (grain
      plus potato by-product), 10% supplement, and 7% alfalfa (DM basis) for an average
      of 130 d. Longissimus muscle cuts were used for Warner-Bratzler shear force
      determination (four steers per pen) and evaluation (two steers per pen) by a 10
      member trained laboratory panel, a professional flavor/texture profile panel, and
      by consumer panels. Diet did not affect (P > .10) Warner-Bratzler shear force or
      trained laboratory panel tenderness, juiciness, and flavor intensity scores.
      Flavor/texture profile panel scores indicated feeding a corn-based diet as
      opposed to barley-based diet produced a more appropriate well-balanced and well
      blended beef flavor and texture. However, the magnitudes of the differences were
      relatively small, and flavor and texture amplitude ratings for both barley- and
      corn-fed beef were well above average. Beef from steers fed 10 or 20% potato by
      product had lower (P < .05) incidences of inappropriate aromatics and
      aftertastes, which may have a slightly beneficial effect on beef flavor, but
      flavor amplitude was not affected (P > .05) by level of potato. Moreover,
      consumer panel overall acceptability scores were not affected by diet. Thus,
      feedlot diets containing corn or barley with or without potato by-product should
      result in palatable beef products.

PMID- 10907827
TI  - National Beef Tenderness Survey-1998.
AB  - Fifty-six retail stores representing 15 retail chains and 14 foodservice
      facilities in eight U.S. cities were sampled to determine the tenderness of beef
      steaks at retail and foodservice levels based on Warner-Bratzler shear (WBS)
      values and consumer evaluation panels. Retail consumer panels were conducted at
      five universities. Each retail and foodservice steak was evaluated using 10-point
      scales. Steaks were divided into the following quality groups for statistical
      analysis: Prime, Top Choice, Choice, Select, and Lean or No Roll. Quality group
      had no effect on WBS values of retail clod, chuck roll, top round, bottom round,
      eye of round, top loin, top sirloin, or ribeye steaks but did (P < .05) affect
      values for the T-bone/porterhouse. The percentages of retail top round, eye of
      round, and bottom round steaks with a WBS force > 3.9 kg were 39.6, 55.9, and
      68.0, respectively. Foodservice ribeye, top loin, and top sirloin steaks had WBS
      values less than 3.4 kg for all quality groups, with Prime ribeye steaks having
      lower (P < .05) WBS values than ribeyes from the other quality groups. With the
      exception of the retail ribeye steak, quality group did not affect consumer
      sensory ratings of retail and foodservice steaks. Average postfabrication aging
      times were 32 d for foodservice subprimals and 19 d for retail cut subprimals.
      These data indicate that improvements in the tenderness of retail cuts from the
      round are needed. Finally, quality group had little or no effect on consumer
      sensory evaluations and WBS values of retail and foodservice steaks used in this
      study.

PMID- 10907828
TI  - Bovine placental protease specificity toward muscle connective tissue proteins.
AB  - Enzymes currently used to tenderize meat are not substrate-specific, resulting in
      extensive myofibrillar protein degradation that often produces an undesirable
      texture. Bovine placental metalloproteases, which selectively hydrolyze
      connective tissue proteins while leaving myofibrillar proteins intact, may
      tenderize meat without causing texture problems. Therefore, our objective was to
      extract and crudely purify bovine metalloproteases from bovine placenta for
      possible use as tenderizers in meat systems. Enzymes were extracted from
      homogenized tissue and purified by ammonium sulfate precipitation. Samples were
      collected before (crude enzyme) and after gel filtration on a Sephadex G-100
      column. Spectrophotometric analysis identified one major peak (filtered enzyme).
      Gelatin, casein, and type I acid-soluble collagen zymography were used to
      determine substrate specificity. Beef myofibrillar proteins were incubated with
      crude and filtered enzyme fractions, enzymes quenched, and substrate degradation
      visualized using SDS-PAGE. Active gelatinases and collagenases exhibiting
      molecular weights of 57 to 65 kDa were detected on zymograms. Banding patterns
      from crude enzyme indicated two enzymes with both gelatinase and collagenase
      activity and a third enzyme with gelatinase activity only. Banding patterns from
      filtered enzyme indicated two enzymes with both gelatinase and collagenase
      activity. Proteolytic activity was not detected with casein, actin, or myosin
      heavy-chain substrates. Due to specificity for collagen and gelatin, these
      enzymes may be capable of improving the tenderness of certain cuts relatively
      high in connective tissue, while avoiding myofibrillar protein hydrolysis.

PMID- 10907829
TI  - Implant strategies during feeding: impact on carcass grades and consumer
      acceptability.
AB  - Anabolic growth promotants influence beef grade factors and Warner-Bratzler shear
      force of steaks. No study has assessed the consumer acceptability of beef derived
      from implanted cattle. This study determined beef carcass grades and consumer
      acceptability for cooked beef from unimplanted (control) cattle and from cattle
      implanted with one of seven different implant strategies (initial implant/implant
      at 59 d = Encore & Component T-S/no implant, Ralgro/Synovex Plus, Ralgro/Revalor
      S, Revalor-S/Revalor-S, Revalor-S/no implant, no implant/Synovex Plus, and
      Synovex Plus/no implant). British crossbred steers (n = 448) were allocated
      randomly into one of eight pens for each of the control and seven treatment
      groups. Carcass quality and yield grade (n = 403) and Warner-Bratzler shear force
      (n = 298) data were collected by trained personnel. Twenty steaks per control or
      treatment group were selected randomly for use in consumer sensory evaluation.
      Steaks were evaluated by consumers for overall like, tenderness like, tenderness
      level, flavor like, flavor intensity, and juiciness level using 9-point, end
      anchored hedonic scales. Control carcasses had smaller (P < .05) longissimus
      muscle areas than carcasses in all treatment groups except those receiving Encore
      & Component T S/no implant, Ralgro/Synovex Plus, or Revalor S/no implant. Control
      carcasses had higher (P < .05) marbling scores than carcasses in all treatment
      groups except those receiving Ralgro/Revalor-S or Encore & Component T-S/no
      implant. Steaks from control steers had lower (P < .05) Warner-Bratzler shear
      force values than steaks from steers given Revalor-S/no implant. Consumer ratings
      for tenderness like and tenderness level were influenced (P < .05) by implant
      strategy. Effects of implant strategy on overall like, flavor like, and flavor
      intensity approached significance (P = .07 to .09). Consumers rated steaks from
      unimplanted steers as more tender (tenderness level; P < .05) than steaks from
      all treatment groups except that involving Encore & Component T-S/no implant.
      Consumers rated steaks from unimplanted steers as more desirable (P < .05) for
      tenderness like than steaks from all treatments except those involving Encore &
      Component T-S/no implant or Revalor-S/no implant. Although use of implants in
      this study resulted in heavier hot carcass weights and larger ribeyes, some of
      the implant strategies reduced consumer preference of tenderness of steaks.

PMID- 10907830
TI  - Effect of dietary formates on growth performance, carcass traits, sensory
      quality, intestinal microflora, and stomach alterations in growing-finishing
      pigs.
AB  - Three experiments were conducted to evaluate the effect of adding salts of formic
      acid to diets for growing-finishing pigs. In Exp. 1, 72 pigs (23.1 kg and 104.5
      kg initial and final BW) were used to evaluate the effect of Ca/Na-formate and K
      diformate on performance and carcass traits. Treatments were organized in a 2 x 3
      factorial arrangement with two feeding regimens (limit and semi-ad libitum
      feeding) and three diets (control, .85% Ca/Na-formate, and .8% K-diformate). No
      significant feeding regime x diet interaction was found. The K-diformate diet
      increased overall ADG of pigs compared with the control and Ca/Na-formate diets,
      but had no effect on ADFI or gain/feed (G/F) ratio. Neither K-diformate nor Ca/Na
      formate had any effect on carcass lean or fat content. In Exp. 2, 10 limit-fed
      pigs (24.3 kg and 85.1 kg initial and final BW) were used to study the effect of
      K-diformate on performance and sensory quality of pork. Adding .8% K-diformate to
      diets increased ADG (P < .13) and G/F (P < .04), but had no effect on sensory
      quality of the pork or content of formate in liver, kidney, or muscle tissue of
      pigs. In Exp. 3, 96 limit-fed pigs (27.1 kg and 105 kg initial and final BW) were
      used to determine the effect of adding K-diformate to diets on performance,
      carcass traits, and stomach keratinization and(or) lesions. Adding K-diformate
      (0, .6, or 1.2%) to diets increased ADG and ADFI (linear P < .01). The K
      diformate reduced the percentage of carcass fat (linear P < .03) and fat area in
      the cutlet (linear P < .09) and increased percentage lean in the ham (linear P <
      .01), flank (linear P < .02), loin (linear P < .09), and neck and shoulder
      (linear P < .09). The K-diformate had no negative effect on stomach alterations.
      In Exp. 3, the concentration of coliform bacteria in the gastrointestinal tract
      was evaluated in eight control and eight 1.2% K-diformate-fed pigs. The K
      diformate reduced the number of coliforms in the duodenum (P < .03), jejunum (P <
      .02), and rectum (P < .10) of pigs. In conclusion, K-diformate improved growth
      performance and carcass quality of growing-finishing pigs, whereas Ca/Na-formate
      had no effect. K-diformate had no adverse effect on sensory quality of pork or on
      stomach alteration scores.

PMID- 10907831
TI  - Acute phase responses of pigs challenged orally with Salmonella typhimurium.
AB  - This study evaluated responses of the systemic endocrine stress (cortisol) and
      growth (IGF-I, GH) axes, as well as those of inflammatory mediators
      (prostaglandin E2 [PGE2] and tumor necrosis factor alpha [TNFalpha]), to active
      infection with Salmonella typhimurium. Eighteen crossbred barrows were penned
      individually with ad libitum access to feed and water. After an acclimation
      period, jugular catheters were placed in all animals. Control pigs received
      sterile broth orally (CON, n = 7), whereas the treated pigs (S.TYP, n = 11)
      received 3 x 10(9) cfu of S. typhimurium orally. Plasma was collected at 6-h
      intervals from -48 to 120 h. Body weights, feed intake, and rectal temperatures
      also were monitored. Rectal temperatures were elevated in S.TYP pigs (P < .01)
      relative to CON pigs by 12 h, peaked at 42 h (P < .001), and remained elevated
      throughout the remainder of the study. Feed intake was reduced maximally in S.TYP
      pigs at 48 h (P < .001) and remained reduced through 120 h after the challenge.
      Daily body weight gain also was reduced during the 2 wk following infection (P <
      .001). Plasma cortisol concentrations increased (P < .05) at 18 h after the
      challenge in S.TYP pigs and remained elevated generally until 60 h after
      infection. A marked suppression of plasma IGF-I occurred in S.TYP pigs beginning
      at 30 h after infection (P < .001), and it remained lower through 108 h. Plasma
      GH was not affected consistently by treatment, nor did infection alter plasma
      TNFalpha and PGE2. Taken together, the results reveal that infectious processes
      produce profound alterations in the endocrine stress and the somatotropic axis,
      and this may occur in the absence of significant changes in systemic
      proinflammatory mediators.

PMID- 10907832
TI  - Integrated adrenal, somatotropic, and immune responses of growing pigs to
      treatment with lipopolysaccharide.
AB  - The objective of this research was to provide an integrated look at systemic
      adrenal, somatotropic, and immune responses of growing pigs to challenge with
      lipopolysaccharide (LPS). Weaned pigs were challenged intraperitoneally with 100
      microg/kg BW of LPS or sterile saline, and rectal temperature and blood data were
      collected for 72 h. Daily feed intake also was monitored. Plasma was analyzed for
      concentrations of cortisol, tumor necrosis factor alpha (TNFalpha), the acute
      phase protein haptoglobin, growth hormone (GH), insulin-like growth factor I (IGF
      I), and prostaglandin E2 (PGE2). As expected, LPS decreased feed intake,
      stimulated a febrile response, and activated the hypothalamic-pituitary-adrenal
      (HPA) axis as demonstrated by increased cortisol levels. Cortisol reached maximum
      elevation 2 h after treatment (P < .001) and remained elevated through 12 h (P <
      .001). Circulating TNFalpha was increased by LPS at 2 and 4 h after treatment (P
      < .001), and an apparent (not statistically significant) increase in haptoglobin
      also occurred in challenged animals. The LPS injection suppressed IGF-I by 2 h
      following treatment (P < .01), and circulating IGF-I remained reduced relative to
      controls through 44 h. Overall, GH was increased in LPS-treated pigs (P < .05),
      although the treatment x time interaction was not significant. Plasma PGE2 was
      increased transiently at 2 h (P < .05) and then subsequently suppressed at 4, 8,
      and 12 h following LPS (P < .05). This study provides a comprehensive view of
      systemic effects of LPS on components of the HPA, growth, and immune axes. In
      addition, these are the first data to document changes in circulating PGE2 in
      unrestrained animals during the early hours of the acute phase response to LPS.

PMID- 10907833
TI  - A porcine intrauterine 4-mda component with transforming growth factor-beta
      activity suppresses natural killer cell responses.
AB  - A 4-MDa component, recovered from uterine luminal secretions of gilts on d 15 of
      pregnancy, was assessed for suppression of the lytic responses from natural
      killer (NK) and lymphokine-activated killer (LAK) effector cells. Each cell type
      originated from preparations of peripheral blood lymphocytes (PBL), and the LAK
      cells were generated from the incubation of PBL with interleukin-2. The PBL and
      LAK cells were cultured for 5 d with and without the 4-MDa component. Following
      culture, the cells were incubated (22 h) with NK-sensitive K-562 target cells at
      varying effector:target cell ratios (25:1 to 200:1). Lytic activity was assessed
      with the chromium-51 release assay. Additional experiments were conducted in
      order to determine whether suppressor activity of the 4-MDa component was time
      dependent and associated with transforming growth factor-beta2 (TGF-beta2). For
      effector:target cell ratios combined, the 4-MDa component suppressed the lytic
      activity of PBL but failed to affect the LAK cells. Suppression of NK-mediated
      lysis occurred by d 3 of the 5-d culture period. In addition, suppressor activity
      of the 4-MDa component was reversed by a neutralization antibody to TGF-beta2. In
      conclusion, the 4-MDa component with TGF-beta2 activity suppressed the lytic
      responses of porcine NK cells.

PMID- 10907834
TI  - Effects of temperature and plane of nutrition on beta-adrenergic receptors in
      heart, kidney, and liver of lambs.
AB  - We determined the effects of temperature and feed intake on beta-adrenergic
      receptors (beta-adrenoceptors) in tissues of sheep. Twenty-four lambs were
      exposed during three 5-wk periods to either thermoneutral, control (W; 23+/-2
      degrees C) or cold (C; 0+/-2 degrees C) temperatures and were fed either ad
      libitum (A) or restricted (R) levels of feed intake, resulting in four treatment
      groups: WA, WR, CA, and CR. Hearts, kidneys, and livers were harvested at
      slaughter and binding of [3H]dihydroalprenolol to plasma membrane extracts was
      used to determine densities (B(MAX)) and binding affinities (Kd) of beta1 and
      beta2 adrenoceptors. The B(MAX) values ranged from 12.10 to 201.26 and 3.38 to
      12.30 fmol/mg protein for beta1 and beta2 adrenoceptors, respectively; heart and
      kidney had the highest and lowest values, respectively. Feed restriction reduced
      (P < .05) beta1 and beta2 receptor densities in heart but increased (P < .05)
      beta1 receptor density in kidney and liver. Cold temperature exposure reduced
      beta1 receptor density in heart tissue during feed restriction. The Kd values,
      ranging from 1.32 to 5.98 nM, were increased (P < .05) by cold exposure and feed
      restriction in kidney and liver. Because the effectiveness of hormones is a
      function of their concentrations, binding affinities, and their receptor
      densities, these results imply that cold temperature exposure and feed
      restriction could potentially reduce (in heart) and increase (in kidney and
      liver) metabolic responsiveness of tissues to catecholamines.

PMID- 10907835
TI  - The effect of progesterone alone or in combination with estradiol on follicular
      dynamics, gonadotropin profiles, and estrus in beef cows following calf isolation
      and restricted suckling.
AB  - The effects of calf isolation and restricted suckling on LH pulse characteristics
      and interval to first ovulation (postpartum interval) were studied in 52
      multiparous beef cows, with or without exogenous progesterone. At 30 d
      postpartum, cows were randomly allocated to one of four treatments (n =
      13/treatment): 1) Ad lib, ad libitum access of cows to calves; 2) CI/RS, calf
      isolation/restricted suckling, where suckling was restricted to once daily; 3)
      CI/RS+P4, same as CI/RS but cows received an intravaginal progesterone-releasing
      device at calf isolation for 6 d; or 4) CI/RS+P4+E2, as CI/RS+P4 but the
      intravaginal progesterone-releasing device had a 10-mg estradiol capsule
      attached. Daily ovarian scanning and twice-daily blood sampling were performed
      from d 25 postpartum until the day of second ovulation. A random sample of cows
      from each treatment (n = 31 in total) were blood-sampled at 15-min intervals for
      10 h on d 29, 32, 35, and 38. Ovulatory response to treatment was regarded as
      ovulation of either the dominant follicle growing at d 30 or the subsequent DF.
      There was a treatment x day effect (P = .09) on LH pulse frequency, but neither
      progesterone (CI/ RS+P4) nor progesterone and estradiol (CI/RS+P4+E2) treatment
      suppressed the calf isolation/restricted suckling-induced increase in LH pulse
      frequency. The estradiol capsule (CI/RS+P4+E2) delivered sufficient estradiol to
      delay new follicle wave emergence (treatment x stage; P < .001) and the
      associated preemergence increase in concentrations of FSH (treatment, P < .05) in
      cows treated at the postselection stage of follicle wave development, prolonging
      dominance of the dominant follicle present at treatment initiation (P < .001).
      The number of cows that ovulated in response to treatment was greater (P < .001)
      in cows with calf isolation/restricted suckling than in cows suckled ad libitum.
      Hence, cows assigned to the Ad lib treatment had a longer postpartum interval (P
      < .001) than cows of the other treatments. Exogenous progesterone treatment
      increased the frequency of cows exhibiting clinical signs of estrus at first
      ovulation (P < .001) and reduced the frequency of short estrous cycles (P <
      .001). We conclude that, in beef cows with calves, a 6-d progesterone treatment
      does not suppress the calf isolation/restricted suckling-induced increase in LH
      pulse frequency. Hence, on progesterone withdrawal, the LH pulse frequency is
      sufficient to stimulate first ovulation, accompanied by overt estrous expression
      and elimination of a short estrous cycle in most cows.

PMID- 10907836
TI  - The effect of the plasma glucose level on the abomasal function in dairy cows.
AB  - We have studied the effect of plasma glucose level on the abomasal outflow rate
      of fluid using a hyperinsulinemic glucose clamp technique in dairy cows. Four
      nonpregnant, nonlactating cows were subjected to one of the following treatments:
      hyperinsulinemic normoglycemic clamp; hyperinsulinemic hypoglycemic clamp;
      hyperinsulinemic hyperglycemic clamp; or, as a control, an intravenous infusion
      of .9% sodium chloride in a Latin square design. The cows were previously fitted
      with a permanent fistula in the abomasum and the outflow rate of abomasal fluid
      was determined using Co-EDTA as a marker assuming that the outflow followed first
      order kinetics. The abomasal pH was also registered. Insulin was infused
      continuously through a jugular catheter at a rate of 4.8 mU. kg(-1)min(-1) for
      2.5 h in the three clamp treatments. A glucose solution was infused through the
      catheter at a variable rate to achieve a circulating concentration, near the
      preinfusion glucose level (approximately 4.1 mmol/L), 2 mmol/L below the
      preinfusion level, and 2 mmol/L above the preinfusion level for the three
      hyperinsulinemic treatments, respectively. There was a significant effect of
      treatment on the rate of abomasal outflow (P < .001). The rate of abomasal
      outflow was highest for the control treatment (7.8%/min). The slowest outflow was
      observed in the hyperglycemic cows (3.40%/min). The hypoglycemic and
      normoglycemic cows showed intermediate rates (6.0%/min and 5.2%/min,
      respectively). The rate of outflow for the hyperglycemic cows was significantly
      lower than for all the other treatments (P < .01). Abomasal pH was affected by
      treatment (P < .05). The highest pH was observed in the hyperglycemic cows (pH
      2.3). The values for the other three treatments ranged from pH 1.9 to 2.0. These
      results show that hyperglycemia reduced the rate of outflow and increased the pH
      of abomasal fluid in dairy cows. An elevated plasma glucose level thus can be
      considered as a potential risk factor in the pathogenesis of left-displaced
      abomasum.

PMID- 10907837
TI  - Plasma cortisol and ACTH concentrations in the warmblood horse in response to a
      standardized treadmill exercise test as physiological markers for evaluation of
      training status.
AB  - Reliable physiological markers for performance evaluation in sport horses are
      missing. To determine the diagnostic value of plasma ACTH and cortisol
      measurements in the warmblood horse, 10 initially 3-yr-old geldings of the
      Hannovarian breed were either exposed to a training schedule or served as
      controls. During experimental Phase 1, horses were group-housed, and half of the
      horses were trained for 20 wk on a high-speed treadmill. During Phase 2, groups
      were switched and one group was trained for 10 wk as during Phase 1, whereas the
      control group was confined to boxes. During Phase 3 horses were initially
      schooled for riding. Thereafter, all horses were regularly schooled for dressage
      and jumping, and half of the horses received an additional endurance training for
      24 wk. During all phases horses were exposed at regular intervals to various
      standardized treadmill exercise tests. During and after the tests frequent blood
      samples were taken from an indwelling jugular catheter for determination of ACTH
      and cortisol. Treadmill exercise increased both hormones. Maximum ACTH
      concentrations were recorded at the end of exercise, and maximum cortisol levels
      were recorded 20 to 30 min later. Except for one test there were no differences
      in ACTH levels between trained horses and controls. There was no significant
      effect of training on the cortisol response (net increase) to treadmill exercise
      in any of the tests during Phase 1. During Phase 2 higher cortisol responses were
      recorded in controls than in trained horses (P < .05) after 10 wk of training
      (controls confined to boxes). During Phase 3 plasma cortisol responses were also
      higher in controls than in trained horses (P < .05 after 6, 18, and 24, P < or =
      .07 after 12 wk of training) when the inclination of the treadmill was 5%, but
      not at 3%. There was no overlap in net cortisol responses at 30 min between
      trained and untrained horses. An ACTH application after 24 wk of training
      resulted in higher cortisol responses in controls than in trained horses (P < or
      = .05), without any overlap between the groups at 30 min after ACTH. Plasma
      cortisol responses to either treadmill exercise or ACTH injection may be a
      reliable physiological marker for performance evaluation. Prerequisites are
      sufficient differences in training status and sufficient intensity of exercise
      test conditions.

PMID- 10907838
TI  - Influence of castration and estrogen replacement on sexual behavior of female
      oriented, male-oriented, and asexual rams.
AB  - An experiment was conducted to determine whether exogenous estradiol-17beta (E2)
      could restore sexual behavior in castrated rams. The protocol consisted of three
      sequential 6-wk periods during which rams were studied while 1) intact, 2)
      bilaterally castrated, or 3) implanted s.c. with two 7.6-cm silastic implants
      each containing 309+/-16 mg of E2. Rams (classified as female-oriented [FOR, n =
      7], male-oriented [MOR, n = 7], or asexual [n = 7]) were subjected to 30-min
      sexual behavior tests every 2 wk during the ensuing 18 wk. Rams were observed for
      mounts and ejaculations using two ovariectomized, estrous ewes and two intact
      males secured in stanchions. Behavioral data were analyzed using the signed rank
      test, but asexual rams showed no sexual behavior and therefore were not evaluated
      statistically. Jugular blood was collected prior to castration and at the end of
      the 18-wk period, and testicular venous (n = 21) and arterial (n = 8) bloods were
      collected immediately prior to castration. Radioimmunoassay was used to quantify
      systemic levels of estrone (E1), E2, and testosterone (T) and testicular serum
      concentrations of oxytocin (OT). Mounting behavior of MOR and FOR declined after
      castration (P < .05 and P < .10, respectively). Castration reduced the number of
      ejaculations by FOR (P < .05), but not by MOR (P > .10). Mounting behavior of
      castrated MOR and FOR was not affected by E2 treatment relative to that observed
      if castrated only (P > .10). Treatment of asexual rams with E2 did not stimulate
      sexual behavior in these rams. There were no marked differences (P > .10) among
      ram groups with regard to serum concentrations of E1, E2, or T prior to
      castration (overall mean +/- SE, 12.8+/-.7, 7.6+/-.5, and 2,670+/-780 pg/mL,
      respectively) or any difference (P > .10) in systemic concentration of E1 or E2
      among ram groups after rams were implanted with E2 (overall mean +/- SE, 9.7+/-.7
      and 9.0 +/-.7 pg/mL, respectively). Serum concentrations of E2 after implantation
      of the steroid did not differ from those present while rams were intact (P >
      .10). Testicular venous and arterial serum concentrations of OT were low and did
      not differ within or between rams. These results suggest that restoration of E2
      concentrations to physiological levels in castrated adult rams (regardless of
      sexual orientation) cannot stimulate or reestablish sexual behaviors to levels
      observed prior to castration.

PMID- 10907839
TI  - A two-sample method for assessing growth hormone response to growth hormone
      releasing hormone challenge: use as a predictor of gain in beef bulls.
AB  - In two experiments, Black Angus bulls were challenged at weaning with GHRH analog
      and evaluated for their GH response to determine whether GH response can predict
      subsequent growth characteristics. The GH response was determined by measuring GH
      in blood serum collected 0 and 10 min after GHRH injection (Exp. 1: 1.5
      microg/100 kg BW human GHRH, n = 34; Exp. 2: 1.5 and 4.5 microg/100 kg BW bovine
      GHRH [treatments LGHRH and HGHRH, respectively] administered 3 h after a 4.5
      microg/100 kg BW "clearance dose" of GHRH, n = 38]. In Exp. 1, GH response did
      not predict growth or carcass measurements. In Exp. 2, GH response to LGHRH was
      positively related to ADG (R2 = .18; P = .007) during a 112-d controlled feeding
      trial. In addition, there was a tendency for bulls with a greater GH response to
      HGHRH to exhibit greater ADG than animals with a low response. However, GH
      response to GHRH was not related to changes in hip height (HH) or carcass
      ultrasound measurements at d 112 of the growth performance trial. Response of GH
      to repeated GHRH challenges was consistent within animal over time (r = .47; P =
      .003). The use of a clearance dose 3 h prior to GHRH challenge improved the
      relationship between GH response and ADG. Results of this study suggest that GH
      response to GHRH challenge is a useful tool for identifying beef bulls with
      superior growth potential.

PMID- 10907840
TI  - Free and peptide amino acid net flux across the rumen and the mesenteric- and
      portal-drained viscera of sheep.
AB  - This experiment was conducted to determine the significance of the peptide amino
      acid (PAA) contribution to amino acid (AA) net flux in the portal vein and to
      evaluate the capacity for peptide absorption in the different segments of the
      gastrointestinal tract of ruminants. Four sheep (64+/-3 kg BW) were fitted with
      catheters and blood flow probes, allowing AA net flux measurements across the
      portal- (PDV) and mesenteric (MDV)-drained viscera and the rumen. Sheep were fed
      at maintenance a diet containing hay and extruded peas (70:30). Peptide
      absorption was investigated by a dose infusion of a mixture of peptides (casein
      hydrolysate, Pro-Phe, beta-Ala-His, Gly-Gly) into the rumen. Control and
      postinjection net fluxes of plasma free amino acids (FAA) and PAA were
      determined. The concentration of plasma PAA was determined by quantification of
      amino acids before and after acid hydrolysis of samples first submitted to
      chemical deproteinization and ultrafiltration (3-kDa cut-off filter). During the
      control period a significant net release (12 mmol/h) of PAA was observed across
      the PDV, which accounted for 35% of the sum of FAA and PAA net fluxes. This PDV
      flux of PAA mainly resulted from a MDV release of PAA (15 mmol/h). The net flux
      of total PAA across the ruminal wall was not significantly different from zero,
      but uptake of peptide Ile and release of peptide Gly were observed. The injection
      into the rumen of the peptide mixture increased the net release of peptide
      essential AA (EAA) across the MDV (P < .05) and the PDV (P < .10), and of peptide
      Pro and Phe across the non-MDV (P < .10). Peptide Ile uptake by the rumen tissues
      was decreased by the injection (P < .05). Significant increases in peptide Pro
      and Gly arterial concentrations were observed (P < .05). The 3-Ala-His and Gly
      Gly arterial concentrations and net fluxes across the PDV were not affected by
      their injections into the rumen. This study showed that PAA may contribute
      significantly to AA flux across the PDV of sheep, and that part of this flux can
      probably be attributed to peptide absorption from the gut lumen. When high
      concentrations of peptides are generated in the rumen the possibility of peptide
      absorption before the jejunum has to be considered.

PMID- 10907841
TI  - Forage systems for production of stocker steers in the upper south.
AB  - The southern states produce large numbers of beef calves that are generally
      weaned and sold in autumn. Keeping calves in this region beyond weaning to graze
      high-quality forages through a stocker cattle phase could improve profitability.
      Autumn-weaned Angus crossbred steers were allocated by breeding and weight to
      four forage systems that began in mid-November and continued through mid-October
      as follows: System 1, tall fescue (Festuca arundinacea Schreb.) and Kentucky
      bluegrass (Poa pratensis L.)-white clover (Trifolium repens L.); System 2, tall
      fescue, caucasian bluestem (Bothriochloa caucasica [Trin.] C. E. Hubbard) and
      tall fescue-red clover (Trifolium pratense L.); System 3, orchardgrass-alfalfa
      and bluegrass-white clover; and System 4, rye (Secale cereale L.), soybeans
      (Glycine max)-foxtail millet (Setaria italica), and bluegrass-white clover. All
      steers were supplemented with hay or silage previously cut from their respective
      systems when forage for grazing was limited. System 2 which used stockpiled tall
      fescue for winter grazing and caucasian bluestem for summer forage plus fescuered
      clover for hay and grazing in a three-paddock system, resulted in greater (P <
      .01) gain per hectare and per steer, more grazing days, and reduced stored forage
      requirements and produced more surplus feed than the other systems tested. Gains
      per hectare for Systems 1 through 4 were 454, 554, 472, and 487 kg (SE = 18),
      respectively. Harvested forage from Systems 1, 2, and 3 met needs for stored
      forages but System 4 required additional "purchased" hay. Stored forage was fed
      for 61, 38, 112, or 104 d for Systems 1 through 4, respectively. Within the
      physio-climatic region of this experiment, a simple three-paddock system based on
      cool- and warm-season perennial forages could improve beef production per unit of
      land area while reducing inputs of labor and equipment.

PMID- 10907842
TI  - Intake and chewing behavior of steers consuming switchgrass preserved as hay or
      silage.
AB  - Effect of preservation method on intake and chewing behavior was examined using a
      first, late vegetative harvest (mid-June) of Kanlow switchgrass (Panicum virgatum
      L.). For silage (S), forage was harvested with a commercial field chopper (1.5 to
      4 cm average chop length) and ensiled directly in silos 1.2 m in diameter and 3.6
      m in height. For hay (H), forage was harvested with a flail-chopper (7 to 15 cm
      average chop length) and cured as hay in a drier at 77 degrees C. Diets of H and
      S were fed to six Hereford steers (338+/-5 kg) in a single crossover experiment.
      Chewing behavior was monitored for 4 d with a computerized system. At feeding, H
      was higher in DM and contained greater concentrations (DM basis) of NDF, CP, and
      hemicellulose, but lower concentrations of ADF and cellulose, and had lower in
      vitro DM disappearance values. Steers fed S had higher intakes of DM (P < .02)
      and NDF (P < .04) and consumed less water from the water supply (P < .01) than
      animals fed H. However, total amount of water (from water supply and feed)
      consumed per kilogram of DMI did not differ between diets. Crude protein intake
      was similar between diets. Preservation method had no effect on eating time,
      number of boli ruminated, bolus duration, and number of rumination chews per
      bolus. Steers fed S made fewer eating chews (P < .10) and ruminated for a longer
      time (P < .05) while making a greater number of rumination chews (P < .04) than
      steers fed H. Rumination intercycle time was slightly shorter in steers fed H (P
      < .05) than in steers fed S. When expressed per kilogram of NDF intake, steers
      fed S spent less time eating (P < .03) and made fewer eating chews (P < .02) than
      steers fed H; however, rumination time, number of rumination chews, and number of
      boli ruminated were not affected by preservation method. Steers fed S ingested
      feed at a greater rate (P < .03), excreted smaller fecal particles (P < .03), had
      meals of shorter duration (P < .06), spent less time eating during main meals
      (meals following feed distribution: P < .05), had more rumination periods (P <
      .01), and a shorter morning (P < .06) latency time (interval between end of main
      meal and onset of rumination) than steers fed H. These results indicate that
      preservation method with its concomitant differences in chop length affected
      forage chemical composition and voluntary intake, and that differences in chewing
      behavior occurred mostly during eating.

PMID- 10907843
TI  - Sheep rumen metabolic development in response to age and dietary treatments.
AB  - This study examined the time course of rumen metabolic development in the absence
      of solid feed consumption and the effect of delayed solid feed consumption on
      sheep rumen development. Twenty-seven lambs consumed milk replacer until
      slaughter at nine ages from 1 to 84 d (milk group). Three additional lambs
      consumed milk replacer from 1 to 48 d. From 49 d until slaughter at 84 d, these
      lambs were weaned onto solid feed (fed group). At slaughter, rumen contents were
      removed for VFA analysis and rumen epithelium was preserved for morphological
      examination. Rumen epithelial cells were isolated and incubated in media
      containing 2.5 mM U-[14C]-glucose or 10 mM 1-[14C]-butyrate. Rumen VFA
      concentrations did not change with age in lambs given milk replacer. At 84 d of
      age, intraruminal VFA concentrations were elevated in lambs consuming solid feed
      compared to 84-d-old lambs given milk replacer (P < .05). The number of ruminal
      papillae per square centimeter decreased (P < .05) while papillae length and
      width did not change significantly with age in rumen epithelium from lambs given
      milk replacer. At 84 d of age, rumen epithelium from lambs in the fed group had
      fewer and larger papillae/per square centimeter than rumen epithelium from lambs
      given milk replacer (P < .05). Rates of glucose and butyrate oxidation and
      acetoacetate and lactate production by rumen cells isolated from lambs given milk
      replacer did not change with age. Beta-hydroxybutyrate (BHBA) production was
      undetectable before 42 d of age in lambs given milk replacer and increased to
      levels found in conventionally raised adults by 84 d. At 84 d there were no
      differences in rates of glucose and butyrate oxidation or acetoacetate and
      lactate production by rumen cells between the two treatment groups. Thus, the
      change in substrate oxidation from glucose to butyrate, indicative of rumen
      metabolic maturation, does not occur in the absence of solid feed consumption.
      However, the development of rumen ketogenesis, as evidenced by increased BHBA
      production, does occur in the absence of solid feed consumption. Delaying the
      initiation of solid feed consumption results in rumen morphological development
      but does not stimulate rumen metabolic development. Increased intraruminal VFA
      concentrations, earlier exposure to VFA, or a longer period of exposure to VFA
      may be required to induce the genes responsible for rumen metabolic development.

PMID- 10907844
TI  - Limiting amino acids for growing Holstein steers limit-fed soybean hull-based
      diets.
AB  - Studies were conducted to determine limiting amino acids (AA) for cattle limit
      fed soybean hull-based diets. Ruminally cannulated Holstein steers were
      maintained in metabolism crates, fed the same basal diet (73% soyhulls, 19%
      alfalfa, DM basis), and given the same intraruminal infusions (400 g/d acetate;
      to supply energy without increasing microbial protein supply). Treatments were
      infused abomasally. In Exp. 1, steers (200 kg) were provided 1) water, 2) 10 g/d
      of methionine (MET), or 3) a mixture of 10 essential AA (10AA). Nitrogen
      retention (13.7 g/d) was greatest (P < .05) for steers receiving 10AA. Steers
      receiving MET (7.9 g/d) had greater (P < .05) N retention than control steers
      (5.4 g/d). In Exp. 2, steers (200 kg) were provided 10AA or 10AA with L-Lys
      deleted from the mixture. Steers receiving 10AA tended (P < .09) to have greater
      N retention (19.0 g/d) than those receiving no lysine (16.3 g/d). In Exp. 3,
      steers (194 kg) were provided 10AA or 10AA with L-Thr deleted from the mixture.
      Nitrogen retention was not affected by removal of threonine. In Exp. 4, steers
      (152 kg) were provided 10AA or 10AA with L-His, L-Trp, L-Arg, L-Phe, or branched
      chain AA (L-Leu, L-Ile, and L-Val) removed. Nitrogen retention was reduced (P <
      .05) by removal of either L-His or the branched-chain AA. For steers limit-fed
      soybean hull-based diets, methionine was first-limiting; histidine, at least one
      of the branched-chain AA, and possibly lysine were also limiting.

PMID- 10907845
TI  - Analysis of unique variable region of a plant root inducing plasmid, pRi1724, by
      the construction of its physical map and library.
AB  - Ri plasmids in Agrobacterium rhizogenes specifically induce the hairy root
      syndrome on various dicotyledonous plants. Its T-DNA transfer system as well as
      those of Ti plasmids have successfully provided the fundamental technique to
      introduce exogenous genes into plants. To study the Ri genome structure, we
      constructed a complete BamHI physical map and a lambda library of pRi1724 of A.
      rhizogenes strain 1724. By using these, we carried out the complete sequence of
      the 74-kb region between the right border of T-DNA and tra operon, which is the
      highly variable region (VAR) among Ri and Ti plasmids. As a result, we found
      three kinds of putative ABC-type transport operons, histidine utilization operon,
      glycerol utilization operon and two chemoreceptor genes. In addition, a virulence
      related gene, tzs was located independently of the vir region.

PMID- 10907846
TI  - Comparison of expressed sequence tags from male and female sexual organs of
      Marchantia polymorpha.
AB  - A total of 935 expressed sequence tags (ESTs) from male immature sexual organ
      were determined, of which 600 ESTs were assembled into 110 non-redundant groups,
      resulting in 445 unique EST sequences. Of these, 244 sequences shared significant
      similarities to known nucleotide or amino acid sequences in other organisms. The
      remaining 201 unique sequences showed no significant matches and thus are likely
      to be novel transcripts. ESTs from male and female immature sexual organs of a
      liverwort, Marchantia polymorpha, were compared to characterize gene expression
      patterns during sex differentiation. Ninety-nine male ESTs turned out to be
      common genes found also in the female library. Interestingly, one of the ESTs
      found only in male shows a significant similarity to the transformer-2 gene
      involved in sex determination in Drosophila. In female, several unique lectin
      ESTs were found that are not present in the male library.

PMID- 10907847
TI  - A large scale analysis of cDNA in Arabidopsis thaliana: generation of 12,028 non
      redundant expressed sequence tags from normalized and size-selected cDNA
      libraries.
AB  - For comprehensive analysis of genes expressed in the model dicotyledonous plant,
      Arabidopsis thaliana, expressed sequence tags (ESTs) were accumulated. Normalized
      and size-selected cDNA libraries were constructed from aboveground organs, flower
      buds, roots, green siliques and liquid-cultured seedlings, respectively, and a
      total of 14,026 5'-end ESTs and 39,207 3'-end ESTs were obtained. The 3'-end ESTs
      could be clustered into 12,028 non-redundant groups. Similarity search of the non
      redundant ESTs against the public non-redundant protein database indicated that
      4816 groups show similarity to genes of known function, 1864 to hypothetical
      genes, and the remaining 5348 are novel sequences. Gene coverage by the non
      redundant ESTs was analyzed using the annotated genomic sequences of
      approximately 10 Mb on chromosomes 3 and 5. A total of 923 regions were hit by at
      least one EST, among which only 499 regions were hit by the ESTs deposited in the
      public database. The result indicates that the EST source generated in this
      project complements the EST data in the public database and facilitates new gene
      discovery.

PMID- 10907848
TI  - Cbfa1, an essential transcription factor for bone formation, is expressed in
      testis from the same promoter used in bone.
AB  - Cbfa1 is an essential transcription factor for bone formation, but its
      transcripts have also been detected in thymus and testis. To elucidate the
      expression of Cbfa1 in testis, we isolated Cbfa1 cDNA from mouse testis. First we
      examined the length of the transcripts expressed in mouse testis by Northern
      hybridization. Using a cDNA probe that can detect both Type-I and Type-II Cbfa1
      (Type-I: originally reported as Pebp2alphaA by Ogawa et al.; Type-II: originally
      reported as til-1 by Stewart et al.), 1.8-kb transcripts were detected in testis,
      and larger transcripts (6.3 kb and 7.4 kb) in T-cell lines, thymus and bone.
      Using a Type-II specific probe (bone isoform-specific probe), surprisingly, 1.8
      kb testis transcript(s) were detected as well as those (6.3 kb) found in bone. In
      addition, the transcription start site in mouse testis coincides with one of
      three start sites identified in bone. These results suggest that the testis
      transcript is generated from the same promoter of Type-II Cbfa1, which is thought
      to be active only in osteoblasts and some chondrocytes. Next, to define the
      difference in length of transcripts, we isolated the Cbfa1 cDNA from mouse
      testis. Sequence analysis of the cDNA showed that alternative splicing around
      exon 2 and poly-adenylation within exon 8 occurred in the testis isoform, which
      produce the smaller transcripts. These data revealed that testis Cbfa1 mRNA is
      transcribed from same promoter used in bones, but the post-transcriptional
      regulation is different between testis and skeletal tissues.

PMID- 10907849
TI  - Isolation and characterization of the gene encoding mouse tax-responsive element
      binding protein (TREB) 5.
AB  - TREB5/hXBP-1/HTF is a basic region leucine zipper protein which binds to a cyclic
      AMP responsive element (CRE)-like element in both human T-cell leukemia virus
      type 1 and human major histocompatibility complex (MHC) class II genes. To
      analyze the structure and transcription regulation of the TREB5 gene, we isolated
      the mouse TREB5 gene and cDNA. The mouse TREB5 gene contains five exons and four
      introns and spans approximately 5 kb. The deduced amino acid sequence of mouse
      TREB5 exhibited 77% and 94% homology to human and rat TREB5, respectively. The b
      zip structure is completely conserved in mouse, rat and human. Southern blot
      analysis of the mouse genomic DNA demonstrated that positive bands exactly
      coincide with those expected from sequences of the cloned genes, indicating that
      the mouse TREB5 gene is present as a single copy. The transcription start site of
      the mouse TREB5 gene was mapped to -15 bp upstream from the ATG initiation codon.
      Promoter analysis of serial deletion mutants revealed that the -142 bp upstream
      region is the minimum sequence to promote mouse TREB5 gene expression and that
      the -1.0 kb upstream region is required for full promoter activity.

PMID- 10907851
TI  - A novel gene, DSCR5, from the distal Down syndrome critical region on chromosome
      21q22.2.
AB  - Based on a detailed sequence of the distal Down syndrome critical region (DSCR),
      we predicted and molecularly cloned a novel gene, designated DSCR5. We determined
      the sequences of expressed sequence tags (ESTs) that almost matched the predicted
      cDNA sequence of DSCR5. Northern blot analysis showed that DSCR5 is expressed in
      several tissues including the liver, skeletal muscle, heart, pancreas and testis.
      To determine the 5'-end of DSCR5, the oligo-capping method was employed.
      Combining the EST sequence data and that from the oligo-capping experiments, we
      obtained the full-length cDNA sequence of DSCR5. DSCR5 had at least four types of
      alternatively spliced variants. According to the number of exons, they could be
      classified into two subtypes: DSCR5alpha and DSCR5beta. DSCR5alpha includes three
      splice variant subtypes, DSCR5alpha1, alpha2 and alpha3, which each has different
      first non-coding exon. In addition, the most abundantly isolated form,
      DSCR5alpha1, shows microheterogeneity of the mRNA start site. Comparison of the
      sequences between the predicted cDNA and the molecularly cloned cDNA revealed
      that the computer programs had limited validity to correctly predict the terminal
      exons. Thus, molecular cloning should always be required to complement the
      inadequacy of the computer predictions.

PMID- 10907850
TI  - Sequence-based structural features between Kvlqt1 and Tapa1 on mouse chromosome
      7F4/F5 corresponding to the Beckwith-Wiedemann syndrome region on human 11p15.5:
      long-stretches of unusually well conserved intronic sequences of kvlqt1 between
      mouse and human.
AB  - Mouse chromosome 7F4/F5 is a syntenic locus of human 11p15.5 in which many
      imprinted genes are clustered. Transmission of aberrant human 11p15.5 or
      duplicated 11p causes Beckwith-Wiedemann syndrome (BWS) depending on which parent
      the chromosome is derived from. To analyze a syntenic mouse locus corresponding
      to human 11p15.5, mouse BAC contigs were constructed between Nap2 and Tapa1, in
      which 390 kb was sequenced between Kvlqt1 and Tapa1. An unexpected finding was
      that of highly conserved intronic sequences of Kvlqt1 between mouse and human,
      and their homologies came up to at least 160 kb because the length of this gene
      extended to 350 kb, suggesting the possibility of some functional constraint due
      to transcriptional and/or post-transcriptional regulation of this region. Many
      expressed sequence tags (ESTs) were mapped on this locus. Three genes, Lit1
      (Kvlqt1-AS), Mtr1 and Tssc4, were identified and characterized. Lit1 is an
      antisense-transcript of Kvlqt1 and paternally expressed and maternally methylated
      throughout the developmental stage. The position where Lit1 exists corresponded
      to a highly conserved region between mouse and human. This transcript extends at
      least 60 kb from downstream to upstream of exon 10 in Kvlqt1. Tssc4 and Mtr1
      carried putative open reading frames but neither was imprinted. Further
      characterization of this locus based on the sequence comparison between mouse and
      human will contribute valuable information towards resolving the mechanism of the
      occurrence of BWS and the associated childhood tumor.

PMID- 10907852
TI  - Analysis of expressed sequence tags of flower buds in Lotus japonicus.
AB  - In order to study gene expression in a reproductive organ, we constructed a cDNA
      library of mature flower buds in Lotus japonicus, and characterized expressed
      sequence tags (ESTs) of 842 clones randomly selected. The EST sequences were
      clustered into 718 non-redundant groups. From BLAST and FASTA search analyses of
      both protein and DNA databases, 58.5% of the EST groups showed significant
      sequence similarities to known genes. Several genes encoding these EST clones
      were identified as pollen-specific genes, such as pectin methylesterase,
      ascorbate oxidase, and polygalacturonase, and as homologous genes involved in
      pollen-pistil interaction. Comparison of these EST sequences with those derived
      from the whole plant of L. japonicus, revealed that 64.8% of EST sequences from
      the flower buds were not found in EST sequences of the whole plant. Taken
      together, the EST data from flower buds generated in this study is useful in
      dissecting gene expression in floral organ of L. japonicus.

PMID- 10907853
TI  - Structural analysis of Arabidopsis thaliana chromosome 3. II. Sequence features
      of the 4,251,695 bp regions covered by 90 P1, TAC and BAC clones.
AB  - To deduce the entire sequence of the top arm of the Arabidopsis thaliana
      chromosome 3, the sequence determination was performed on a total of 90 P1, TAC
      and BAC clones chosen according to our sequencing strategy. Sequence features of
      the resulting 4,251,695 bp regions were analyzed with various computer programs
      for similarity search and gene modeling. As a result, a total of 941 potential
      protein-coding genes were identified. The average density of the genes identified
      was 1 gene per 4210 bp. Introns were observed in 73% of the genes, and the
      average number per gene and the average length of the introns were 3.6 and 159
      bp, respectively. These sequence features are essentially identical to those of
      chromosomes 3 and 5 in our previous reports. The regions also contained 14 tRNA
      genes when searched by similarity to reported tRNA genes and the tRNA scan-SE
      program. The sequence data and information on the potential genes are available
      through the World Wide Web database KAOS (Kazusa Arabidopsis data Opening Site)
      at http://www.kazusa.or.jp/kaos/.

PMID- 10907854
TI  - Generation of 10,154 expressed sequence tags from a leafy gametophyte of a marine
      red alga, Porphyra yezoensis.
AB  - A total of 10,154 5'-end expressed sequence tags (EST) were established from the
      normalized and size-selected cDNA libraries of a marine red alga, Porphyra
      yezoensis. Among the ESTs, 2140 were unique species, and the remaining 8014 were
      grouped into 1127 species. Database search of the 3267 non-redundant ESTs by
      BLAST algorithm showed that the sequences of 1080 species (33.1%) have similarity
      to those of registered genes from various organisms including higher plants,
      mammals, yeasts, and cyanobacteria, while 2187 (66.9%) are novel. Codon usage
      analysis in the coding regions of 101 non-redundant EST groups showing
      significant similarity to known genes indicated the higher GC contents at the
      third position of codons (79.4%) than the first (62.2%) and the second position
      (45.0%), suggesting that the genome has been exposed to high GC pressure during
      evolution. The sequence data of individual ESTs are available at the web site
      http://www.kazusa.or.jp/en/plant/porphyra/EST/.

PMID- 10907855
TI  - Structurally and functionally distinct mouse hsp70 family members Mot-1 and Mot-2
      proteins are encoded by two alleles.
AB  - The mouse mortalin proteins Mot-1 and Mot-2 differ by two amino acids in their
      carboxy-terminus. These proteins are differentially localized in the cell
      cytoplasm and have contrasting biological activities. The genetic relationship
      between Mot-1 and Mot-2 was deciphered by mouse family analyses. Mot-1 and Mot-2
      segregated in F1 and F2 progeny, providing direct evidence that the two proteins
      are encoded by two alleles.

PMID- 10907856
TI  - The human homologue of flamingo, EGFL2, encodes a brain-expressed large cadherin
      like protein with epidermal growth factor-like domains, and maps to chromosome
      1p13.3-p21.1.

PMID- 10907857
TI  - The histologic classification of 602 cases of feline lymphoproliferative disease
      using the National Cancer Institute working formulation.
AB  - Case information and histologic slides for 688 admissions of feline tissues from
      12 veterinary institutions were assembled and reviewed to determine tissues
      obtained by biopsy or necropsy, age and sex of cat, tumor topography, feline
      leukemia viral antigen status, histologic frequency of mitoses, diagnosis,
      presence of necrosis, and presence and degree of sclerosis. Histologic sections
      were examined to place the lesions in one of the diagnostic categories of the
      National Cancer Institute working formulation (NCI WF) for lymphomas or lymphoid
      leukemia. Correlations between the various factors determined were tested using
      contingency tables and chi-square analysis to provide a statistical comparison
      between the levels of observations determined by case examination with the
      numbers expected from chance alone. Significant correlations (P < or = 0.05) were
      found between diagnosis and tumor topography, the frequency of mitoses, necrosis,
      sclerosis, and age, between mitoses and necrosis, topography, age, and feline
      leukemia viral infection status, between topography and necrosis and age, and
      between leukemia viral status and age. Significant correlations between diagnosis
      and tumor topography included a greater than expected number of cases of acute
      and chronic lymphoid leukemia and multicentric distribution of tumor. Small cell
      lymphomas were more frequent than expected in enteric and cutaneous areas and
      less frequent than expected in mediastinal, renal, and multicentric areas. In
      contrast, the high-grade small noncleaved type of lymphomas was found
      significantly more frequently than expected in the mediastinum and less
      frequently than expected in enteric tissues. In comparing diagnosis and frequency
      of mitoses, the lymphomas classified as low grade by the NCI WF were
      significantly more frequent than expected in the lower categories (0-2/100x) of
      mitoses, and those classified as high-grade lymphomas were more frequent than
      expected in the higher categories (4-8/1OOx) of mitoses. In comparing diagnosis
      and sclerosis, diffuse sclerosis was more frequent than expected for the
      intermediate grade lymphomas of mixed cell type and for the high-grade lymphomas
      of the immunoblastic polymorphous type. In comparing diagnosis and locally
      extensive necrosis, this feature was more frequently observed than expected for
      cases of intermediate grade lymphoma of the small-cleaved cell category and for
      the high-grade lymphoma of the immunoblastic cell type. In comparing mitoses and
      necrosis, the lower grade lymphomas were, in general, characterized by a lower
      frequency of mitoses and a lower incidence of necrosis then would be expected
      from chance alone. In contrast, the higher grade lymphomas were characterized by
      more frequent mitoses and a higher incidence of necrosis. In tests comparing
      mitoses and tumor topography, lymphomas of the alimentary tract were more
      frequently observed than expected in the category with the lowest level of
      mitoses (0-1/100x), whereas lymphomas of the mediastinum and kidney were more
      frequently observed than expected in the categories with a higher level (4-20/
      100x) of mitoses.

PMID- 10907858
TI  - Optimization of immunohistochemical methods using two different antigen retrieval
      methods on formalin-fixed paraffin-embedded tissues: experience with 63 markers.
AB  - Formalin fixation produces cross-links between the proteins and the fixative that
      alter the ability of some antibodies to recognize antigens. We used formalin
      fixed, paraffin-embedded tissues to compare two different antigen retrieval
      methods for 63 antibodies used in the diagnosis of infectious and neoplastic
      diseases of animal species. Eighty-four percent of the antibodies needed some
      type of antigen retrieval for optimal results. Of those antibodies, 67.7% were
      monoclonal and 32.3% were polyclonal. Steam heat was the method of choice for 31
      antibodies. Ten antibodies reacted only with steam heat, but 9 antibodies did not
      react when steam heat was used. Optimal results were obtained with enzyme
      digestion for 22 antibodies. Only 10 antibodies yielded optimal results without
      antigen retrieval; 64% of these antibodies were polyclonal. All antibodies
      against cytokeratins were optimally retrieved with proteinese K. Antigen
      retrieval appears to be necessary for the majority of antibodies when used with
      formalin-fixed, paraffin-embedded tissues.

PMID- 10907859
TI  - Myxobolus cerebralis infection in rainbow trout (Oncorhynchus mykiss) and brown
      trout (Salmo trutta) exposed under natural stream conditions.
AB  - From early April into mid-June 1977, sequential groups of juvenile rainbow trout
      (Oncorhynchus mykiss) and brown trout (Salmo trutta) were each exposed for 10
      days to the parasite Myxobolus cerebralis by immersion in a stream inhabited by
      infected wild trout. Following incubation in a M. cerebralis-free facility, trout
      were subsequently killed, and heads and gill arches were examined by routine
      histologic methods. A grading scale to quantify lesion severity was developed and
      applied. Percentage infected, lesion severity scores, effects of water
      temperature and flow rates on percentage infected and lesion severity scores, and
      resulting pathology were determined for each species at each exposure period. The
      percentage of rainbow trout infected with M. cerebralis was significantly higher
      than the percentage of brown trout infected for each exposure period. The
      percentages of rainbow trout infected in exposure periods later in the calendar
      year were significantly higher than those in earlier periods. The percentages of
      brown trout infected were not significantly different among exposure periods.
      Overall average lesion severity scores were significantly higher in rainbow than
      in brown trout. Lesion severity scores in rainbow trout increased over time (a
      positive correlation with exposure period). Lesion severity scores were not
      significantly different for brown trout among exposure periods. A significant
      correlation existed between water temperature and percentage of rainbow trout
      infected; a significant correlation also existed between water temperature and
      lesion severity scores in rainbow trout. Similar correlations did not exist for
      percentage of brown trout infected or accompanying lesion severity scores. In
      rainbow trout, ventral calvarium was the most common site of M. cerebralis
      replication, followed by gill arches. In brown trout, lesions were virtually
      confined to gill arches. Early lesions consisted of foci of cartilage necrosis
      with small numbers of M. cerebralis developmental stages. More advanced lesions
      consisted of multifocal areas of cartilage necrosis with numerous M. cerebralis
      developmental stages and/or mature myxospores bordered and/or infiltrated by mono
      and multinuclear leukocytes. Lesions in brown trout were smaller and had fewer
      associated leukocytes and M. cerebralis developmental stages and/or mature
      myxospores. Higher infection rates, lesion severity scores, and differences in
      lesion location in rainbow versus brown trout explain in part why numbers of
      rainbow but not brown trout have fallen in western rivers inhabited with M.
      cerebralis-infected trout.

PMID- 10907860
TI  - Comparison of postmortem techniques for the detection of Mycobacterium bovis in
      white-tailed deer (Odocoileus virginianus).
AB  - A retrospective study of various diagnostic postmortem techniques used in a 4
      year surveillance program for detection of Mycobacterium bovis infection in wild
      white-tailed deer (Odocoileus virginianus) was conducted. The tests evaluated
      were routine histopathology, acid-fast staining, detection of acid-fast bacilli
      in culture, and an M. tuberculosis group-specific genetic probe applied to pure
      cultures. Each of these techniques were compared with a reference or "gold
      standard" of mycobacterial culture and identification. Histopathology, the most
      rapid form of testing for M. bovis infection in white-tailed deer samples, had a
      sensitivity of 98% and a specificity of 87%, resulting in a positive predictive
      value of 94%. The detection of acid-fast bacilli by staining was less sensitive
      than histopathology (90%), but its higher specificity (97%) resulted in a
      positive predictive value of 99%. The detection of acid-fast bacilli on culture
      was both highly specific (93%) and sensitive (100%). The group-specific genetic
      probe had the highest sensitivity and specificity and produced results in
      complete agreement with those of mycobacterial culture, suggesting that this
      technique could be used as the new "gold standard" for this particular wildlife
      tuberculosis surveillance program.

PMID- 10907861
TI  - Representational differential analysis detects amplification of satellite
      sequences in postweaning multisystemic wasting syndrome of pigs.
AB  - Representational difference analysis (RDA) was used as a molecular approach to
      identify unique sequences associated with postweaning multisystemic wasting
      syndrome (PMWS) in pigs. Three rounds of subtractive hybridization and
      amplification between driver DNA extracted from normal pigs and tester DNA from
      PMWS-affected animals were performed. The final product corresponding to
      sequences associated with PMWS in pigs was analyzed using agarose gel
      electrophoresis, and 9 fragments were visualized after staining with ethidium
      bromide. Eight recombinants were successively cloned and sequenced, and the
      results were then compared with existing databases. Most of the PMWS clones
      isolated were satellite sequences from pig centrometric regions and 1 was a
      microsatellite sequence. One clone represented a microsatellite sequence, and 2
      clones showed no homology with any gene found in the databases. The sequence
      comparison data did not reveal any homology with an infectious agent such as a
      virus or a bacterium. In the present experimental setting, it was concluded that
      PMWS in pigs triggers molecular changes such as an amplification of genomic
      regions containing repeated sequences.

PMID- 10907862
TI  - Survival of Clostridium difficile and its toxins in equine feces: implications
      for diagnostic test selection and interpretation.
AB  - Although Clostridium difficile is recognized as a cause of enterocolitis in
      horses and humans, there has been little work published regarding the lability of
      C. difficile and its toxins in feces. A significant decrease in recovery of C.
      difficile from inoculated equine fecal samples occurred during storage. Recovery
      after storage in air at 4 degrees C decreased from 76% (37/49) after 24 hours to
      67% (33/49) at 48 hours and 29% (14/ 49) after 72 hours. In contrast to aerobic
      storage, 25 of 26 samples stored anaerobically at 4 degrees C yielded growth of
      C. difficile for 30 days, whereas the organism was only detected for 2.5 +/- 2.52
      days (x +/- SD) in paired samples stored aerobically. The use of an anaerobic
      transport medium was effective in maintaining viability of C. difficile. These
      findings indicate that poor aerotolerance is the reason for the rapid decrease in
      culture yield. In contrast to C. difficile organisms stored aerobically at 4
      degrees C, C. difficile toxins were considerably more stable and could be
      detected by enzyme-linked immunosorbent assay in both broth and inoculated fecal
      samples for at least 30 days. The poor survival of C. difficile but the stability
      of its toxins when feces are stored aerobically must be considered when
      submitting samples for diagnosis of C. difficile-associated enterocolitis in
      horses and when interpreting laboratory results.

PMID- 10907863
TI  - Analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western
      blot of nonspecific and specific viral proteins frequently detected in different
      antigen preparations of bovine leukemia virus.
AB  - Bovine leukemia virus (BLV) infection in cattle is seldom manifested clinically,
      and is routinely diagnosed by serologic tests such as enzyme-linked immunosorbent
      assay or Western blot (WB). Because of the difficulty in interpreting WB results,
      the aim of the present study was to determine which of the bands observed in WB
      were specifically produced by BLV and which corresponded to nonspecific proteins,
      either derived from medium components or of a cellular nature. Five different BLV
      antigen preparations from 2 cell lines (FLK-BLV and BLV-bat2) frequently used for
      the production of BLV antigen were compared. The protein profiles of these
      antigen preparations were analyzed using sodium dodecyl sulfate polyacrylamide
      gel electrophoresis and WB. Fetal calf serum, required for cellular growth and
      important in induction of viral transcription in vitro, was identified as a
      source of irrelevant proteins. In this study, 15 nonspecific protein bands in the
      growth medium were observed. These bands interfered with the interpretation of
      results. A nonspecific protein (25 kD) that was highly reactive in cell lysate
      preparation from BLV-bat2 was also detected. The unequivocal identification of
      protein bands, both specific and nonspecific, seen in WB is important not for
      understanding the protein profile of antigen preparations but also for
      determining if an animal is BLV positive or negative.

PMID- 10907864
TI  - Specificity of four serologic assays for Mycobacterium avium ss paratuberculosis
      in llamas and alpacas: a single herd study.
AB  - An investigation was conducted for Mycobacterium avium ss paratuberculosis
      infections in a research herd of llamas and alpacas. Herd culture-negative status
      was established over a 23-month period by screening any individuals with any
      signs compatible with paratuberculosis (n = 1), high serology values (n = 8), or
      other health and research related reasons (n = 24). There were no M. avium ss
      paratuberculosis isolates from radiometric cultures of multiple tissue and fecal
      samples from these individuals and no known sources of exposure. Paratuberculosis
      is uncommon in North American llamas and alpacas: only 5 cases were identified
      after an extensive search of the Veterinary Medical Data Base, diagnostic
      laboratory records, publication databases, and personal communications.
      Therefore, serum samples from llamas (n = 84) and alpacas (n = 16) in the culture
      negative herd were used to obtain preliminary estimates of test specificity for 3
      enzyme-linked immunoassays (ELISAs) and an agar gel immunodiffusion (AGID) assay
      kit for detecting serum antibodies to M. avium ss paratuberculosis in South
      American camelids. The ELISAs were modifications of established bovine assays for
      antibody detection. With provisional cutoffs, ELISA-A had 52 false positives
      (specificity 48%), ELISA-B had 8 false positives (specificity 92%), ELISA-C had
      two false positives (specificity 98%), and the AGID had 0 false positives
      (specificity 100%). The range of ELISA values for culture-positive llamas and
      alpacas (n = 10) from other herds overlapped the range of values for culture
      negative llamas and alpacas. The accuracy of the ELISAs may be improved by using
      age- and sex-specific cutoffs because uninfected male llamas and alpacas that
      were older than 1 year had higher values for some tests. These tests can be used
      for either llamas or alpacas; the protein-G conjugate ELISA (ELISA-B) may be
      useful for multispecies applications. These assays are best used for rapid
      presumptive diagnoses of llamas and alpacas with diarrhea and weight loss and as
      a screening tool for herds known to be exposed to infection. All seropositive
      results should be confirmed with culture.

PMID- 10907865
TI  - Serodiagnosis of haemonchosis with a somatic antigen (Hc26) in several breeds of
      sheep.
AB  - Sera from 53 sheep belonging to Castellano, Churro, Manchego, and Merino breeds
      were analyzed to test the diagnostic value of a 26-kD antigen from adult
      Haemonchus contortus at prepatency and early and late patency of experimental
      haemonchosis. Animals that received zero, 1, or 2 infections with the parasite
      were tested. In addition, sera from 20 experimentally infected and 10 noninfected
      Texel sheep were used to test the antigen. Sera from 37 infected animals at
      prepatency as well as at patency in primary and secondary infection were found
      positive with the 26-kD antigen. However, sera from 10 animals with the lowest
      worm burdens (second infection) did not recognize the antigen during early
      patency (day 28 postinfection). IgG1 was the only isotype implicated in antigen
      recognition because IgG2, IgA, and IgM, in the same sera, showed no reactivity
      with the peptide. Antigen specificity was confirmed because hyperimmune sera
      against infective larvae and adult stages of the most common gastrointestinal
      nematodes found in natural infections in sheep (Trichostrongylus colubriformis
      and Teladorsagia circumcincta) did not recognize this peptide. The antigen was
      recognized only by anti-adult H. contortus hyperimmune sera and appeared to be
      absent in the L3 parasite stage. In addition, the partial N-terminal amino acid
      sequence of the diagnostic peptide is reported.

PMID- 10907867
TI  - Stability of vitamin E in blood and plasma from cattle, sheep, and pigs.
AB  - The stability of alpha-tocopherol concentrations in sheep, cattle, and pig blood
      and plasma stored at different temperatures was examined. For all species, the
      vitamin was stable for at least 6 days in plasma stored at -20 C, 4 C, and 25 C
      and in blood stored at 4 C and 25 C. For sheep and cattle, the vitamin was stable
      for at least 6 days in plasma stored at 37 C, but it was unstable in blood from
      all species stored at 37 C and in pig plasma stored at 37 C.

PMID- 10907866
TI  - Effects of antigen-retrieval pretreatments for immunohistochemical detection of
      Akabane viral antigen.
AB  - Effects of various antigen-retrieval pretreatment techniques for
      immunohistochemical detection of Akabane virus antigen were examined with
      formalin-fixed, paraffin-embedded tissues taken from mice intracerebrally
      inoculated with the virus. The results indicated that no pretreatment is
      necessary for the detection of the antigen, and excessive enzymatic pretreatment
      of sections may lead to false-negative results.

PMID- 10907868
TI  - Effects of storage conditions and hemolysis on vitamin E concentrations in
      porcine serum and liver.
AB  - Vitamin E (alpha-tocopherol) is an antioxidant vitamin important in protecting
      unsaturated fatty acids in lipid membranes from peroxidation. Variation in
      collection, storage, and shipping conditions of samples can potentially lead to
      breakdown of vitamin E prior to analysis. Therefore, the purposes of this project
      were 1) to determine the stability of vitamin E in refrigerated and frozen
      porcine liver and serum and 2) to evaluate the effects of red blood cell (RBC)
      hemolysis on porcine serum vitamin E concentrations. Porcine liver and
      nonhemolyzed serum were collected and stored refrigerated or frozen. Samples were
      analyzed for vitamin E immediately or on days 2, 3, 7, or 14. In addition,
      porcine RBCs were added to normal serum at concentrations from 1 x 10(6) to 1 X
      10(9) RBC/ml and hemolyzed by freeze-thaw prior to analysis for vitamin E or
      products of lipid peroxidation.

PMID- 10907869
TI  - Bovine abortions associated with Bacteroides fragilis fetal infection.
AB  - Two Santa Gertrudis cattle from a herd of 105 aborted within a 24-hour period.
      Bacteroides fragilis was isolated from tissues of each aborted fetus.
      Histopathologic lesions included placentitis and bronchopneumonia in which gram
      negative, rod-shaped organisms were visible. The diagnostic workup failed to
      reveal other causes of abortion. Anaerobes are rarely implicated in bovine
      abortions, and no other report was found that described abortion in cattle due to
      B. fragilis.

PMID- 10907870
TI  - Fibroleiomyomas of the tubular genitalia in female beluga whales.
AB  - Fibroleiomyomas of the tubular genitalia were diagnosed in 6 of 9 adult female
      beluga whales from the St. Lawrence estuary, Quebec, Canada. These tumors were
      located in the vagina (6 of 6), the cervix (2 of 6), and the uterus (1 of 6).
      Endogenous hormones or xeno-estrogens may be implicated in the occurrence of
      these tumors.

PMID- 10907871
TI  - Congenital cystic disease of the liver and kidney in a pygmy goat.
AB  - A 1-month-old pygmy goat was presented with abdominal distension and hematuria.
      Anemia, leukocytosis, and increased bilirubin and blood urea nitrogen levels
      suggested renal and hepatic disease. Radiographs revealed bilateral renomegaly,
      and ultrasound confirmed bilateral hydronephrosis. Necropsy findings determined
      that the renomegaly was due in part to edema and marked cystic tubular
      distension. Similarly, intrahepatic bile ducts were ectatic. The character and
      distribution of the gross and histologic lesions were consistent with a
      polycystic disorder, presumably congenital, affecting the liver and the kidney.

PMID- 10907872
TI  - Fatal pulmonary edema in white-tailed deer (Odocoileus virginianus) associated
      with adenovirus infection.
AB  - Sporadic sudden deaths in adult white-tailed deer occurred from November 1997
      through August 1998 on an Iowa game farm. Three of the 4 deer necropsied had
      severe pulmonary edema, widespread mild lymphocytic vasculitis, and amphophilic
      intranuclear inclusion bodies in scattered endothelial cells in blood vessels in
      the lung and abdominal viscera. Immunohistochemistry with bovine adenovirus 5
      antisera and transmission electron microscopy demonstrated adenoviral antigen and
      nucleocapsids, respectively, within endothelial cells. Adenovirus was isolated in
      cell culture from 1 of the affected deer. The isolate was neutralized by
      California black-tailed deer adenovirus antiserum. These findings indicate that
      adenovirus should be considered in the differential diagnosis of both black
      tailed and white-tailed deer with pulmonary edema and/or hemorrhagic enteropathy.

PMID- 10907873
TI  - A modified enzyme-linked immunosorbent assay for the detection of avian
      pneumovirus antibodies.
AB  - Avian pneumovirus (APV) infection of turkeys in Minnesota was first confirmed in
      March 1997. Serum samples (n = 5,194) from 539 submissions to Minnesota
      Veterinary Diagnostic Laboratory were tested by a modified enzyme-linked
      immunosorbent assay (ELISA). Of these, 2,528 (48.7%) samples from 269 submissions
      were positive and 2,666 (51.3%) samples from 270 submissions were negative for
      APV antibodies. Most positive samples were from Kandiyohi, Stearns, Morrison, and
      Meeker counties in Minnesota. In addition, 10 samples from South Dakota were
      positive. The sensitivity and specificity of the ELISA test with anti-chicken and
      anti-turkey conjugates were compared by testing field and experimental sera. The
      ELISA test with anti-turkey conjugate was more sensitive than that with anti
      chicken conjugate. The ELISA tests with antigens prepared with APV strains
      isolated from Colorado and Minnesota were also compared. No difference was
      detectable. Currently, the Minnesota Veterinary Diagnostic Laboratory uses an
      antigen prepared from the Colorado isolate of APV and a goat anti-turkey
      conjugate in the ELISA test.

PMID- 10907874
TI  - Development of a reverse transcription-nested polymerase chain reaction assay for
      differential diagnosis of transmissible gastroenteritis virus and porcine
      respiratory coronavirus from feces and nasal swabs of infected pigs.
AB  - Transmissible gastroenteritis virus (TGEV), a coronavirus, replicates in
      intestinal enterocytes and causes diarrhea in young pigs. Porcine respiratory
      coronavirus (PRCV), a spike (S) gene natural deletion mutant of TGEV, has a
      respiratory tissue tropism and causes mild or subclinical respiratory infections.
      Conventional antigen-based diagnostic tests fail to differentiate TGEV and PRCV,
      and a blocking ELISA test to serologically differentiate TGEV/PRCV-infected pigs
      is conducted on convalescent serum retrospectively after disease outbreaks. A
      reverse transcription (RT)-nested polymerase chain reaction (PCR) with primers
      targeted to the S gene deletion region to differentiate TGEV/PRCV was developed.
      The specificity of the RT-nested PCR was confirmed with reference and recent
      field strains of TGEV/PRCV, and its sensitivity was analyzed by testing nasal and
      fecal samples collected from pigs at various days postinoculation (DPI) with TGEV
      or PRCV. Specific PCR products for TGEV/PRCV were detected only with the
      homologous reference or field coronaviruses and for 10-14 DPI of pigs with TGEV
      (feces) or PRCV (nasal samples). The RT-nested PCR assay was more sensitive than
      antigen-based assays on the basis of duration of virus detection in
      experimentally infected pigs and was directly applicable to nasal as well as
      fecal specimens from the field.

PMID- 10907875
TI  - Semi-empirical AM1 calculation of the solvent effect on the fluorescence spectra
      of some dihydroquinolinones.
AB  - The COnductor-like Screening MOdel of solvent-solute interactions of Klamt and
      Schuurmann, COSMO, at the semiempirical AM1 level of MO calculations, augmented
      by limited singles and doubles configuration interaction, proves useful for the
      study of solvent induced shifts of fluorescence spectra. Optimization of geometry
      of ground S0 and excited S1 states for each solvent separately provides estimates
      of the changes of solvation energy accompanying the electron transition process
      and helps the understanding of the related solvent-solute reorganization and
      fluorescence mechanisms.

PMID- 10907877
TI  - Ab initio determination of the roto-torsional energy levels of hydrogen peroxide.
AB  - In the present paper, the roto-torsional energy levels of hydrogen peroxide are
      determined from ab initio calculations performed at the MP4(SDQ)/AUG-cc
      pVTZ//MP4(SDQ)/cc-pVTZ+ ++ level. The rotational levels corresponding to the
      torsional states n = 0 and 1 are determined variationally up to J = 20. The
      flexible model used considers the roto-vibrational interactions. Symmetry
      conditions are included for classifying the levels and reducing the cost of
      diagonalization. Products of contracted torsional basis functions and top
      symmetric solutions are employed as basis functions. The calculated levels are in
      a very good agreement with the experimental data. In addition, the K-doubling has
      been obtained and the levels fitted to the top symmetric equations for
      determining the centrifugal distortion constants. The expectation values of the
      rotational constants at the lowest torsional levels are compared with the
      rotational constants arising from the experimental fit.

PMID- 10907876
TI  - AOTF Raman spectrometer for remote detection of explosives.
AB  - A spectrometer based on acousto-optic tunable filters is developed for use in
      measuring Raman spectra as part of a detection system that is low-cost, reliable,
      and field-portable. The system is coupled with a fiber optic bundle to carry the
      excitation laser light to the sample and to collect the Raman scattered light.
      Spectra of the explosives trinitrotoluene (TNT), cyclotrimethylenetrinitramine
      (RDX), cyclotetramethylenetetranitramine (HMX) and nitroguanidine (NQ) were
      obtained in very short times and are in good agreement with those taken with
      conventional Fourier transform Raman spectrometers. Spectra of mixtures of
      explosives were also obtained and show no overlap of their characteristic Raman
      bands.

PMID- 10907878
TI  - Vibrational spectra of 3,5-dimethylpyrazole and deuterated derivatives.
AB  - The infrared (IR) and Raman spectra of 3,5-dimethylpyrazole have been recorded in
      the vapor, liquid (melt and solution) and solid states. Two deuterated
      derivatives, C5H7N-ND and C5D7N-NH, were also studied in solid state and in
      solutions. Instrumental resolution was relatively low, 2.0 cm(-1) in the IR and
      approximately 2.7 cm(-1) in the Raman spectra. The solids are made of cyclic
      hydrogen-bonded trimers. These trimers, present also in chloroform and acetone
      solutions, give rise to characteristic high absorption IR spectra in the 3200
      2500 cm(-1) region, related to Fermi resonance involving nu(NH) vibrations. Bands
      from trimers are not present in water solutions but these solutions show spectral
      features similar in several ways to those of the trimer, attributable to solvent
      bonded complexes. Evidence of H-bonding interactions with the other solvents is
      also visible in the high-frequency region. The two very intense bands in the
      Raman spectra of the solids appearing at 115 and 82 cm(-1) in the parent compound
      are also connected with a trimer formation. To interpret the experimental data,
      ab initio computations of the harmonic vibrational frequencies and IR and Raman
      intensities were carried out using the Gaussian 94 program package after full
      optimization at the RHF/6-31G* level for the three monomeric compounds as well as
      for three models of the trimer, with C3h, C3 and C1 symmetry. The combined use of
      experiments and computations allow a firm assignment of most of the observed
      bands for all the systems. In general, the agreement between theory and
      experiment is very good, with the exception of the IR and Raman intensities of
      some transitions. Particularly noticeable is the failure of the theoretical
      calculation in accounting for the high intensity of the Raman bands of the solid
      about 115 and 82 cm(-1).

PMID- 10907879
TI  - The effect of ethynyl substitution and cyclopenta fusion on the ultraviolet
      absorption spectra of polycyclic aromatic hydrocarbons.
AB  - We have examined the UV spectra of six newly-synthesized ethynyl-PAH (1
      ethynylnaphthalene, 5-ethynylacenaphthylene, 1-ethynylanthracene, 9
      ethynylphenanthrene, 3-ethynylfluoranthene, and 1-ethynylpyrene) and five
      corresponding CP-PAH (acenaphthylene, aceanthrylene, acephenanthrylene,
      cyclopenta[cd]fluoranthene, and cyclopenta[cd]pyrene) and have found the
      following systematic behavior: ethynyl-substitution results in average
      bathochromic shifts of 5 nm for the lower-wavelength beta- and beta'-bands and of
      18 nm for the higher-wavelength p-band, as well as an amplification of the p-band
      with respect to the beta-band; the addition of a peripheral cyclopenta ring
      results in average bathochromic shifts of 7 nm in the beta-band, 16 nm in the
      beta'-band, and 44 nm in the p-band, compared to the wavelengths in the
      corresponding unsubstituted PAH. The addition of a cyclopenta ring also decreases
      the resolution of vibrational fine structure in the cases where the fine
      structure is particularly intense in the spectrum of the unsubstituted PAH. The
      effects of ethynyl substitution on the UV spectra of PAH are sufficiently
      consistent that new ethynyl-PAH should be identifiable based on their UV spectra
      alone.

PMID- 10907880
TI  - Study on using I- as heavy atom perturber in cyclodextrin-induced room
      temperature phosphorimetry.
AB  - A cyclodextrin induced room temperature phosphorimetry (CD-RTP) for determine
      beta-NOA, which using I- as a heavy atom perturber (HAP) and sodium sulfite as a
      deoxygenator, was developed. The phosphorescence peak wavelength maxima
      lambda(ex)/lambda(em) = 287/496,521 nm. The analytical curve of beta-NOA gives a
      linear dynamic range of 2.0 x 10(-7)-6.0 x 10(-6) mol/l and a detection limit of
      4 x 10(-8) mol/l. The relative standard deviation (RSD; n = 7) was 3.2% for the
      4.0 x 10(-6) mol/l beta-NOA in spiked apple samples. The influence of I-
      concentration on RTP lifetime of beta-NOA was studied in detail, the static Stern
      Volmer equation for phosphorescence was derived and the luminescence kinetic
      parameters were calculated. It is found that the relation between I-
      concentration (x) and RTP lifetime (tau) can be expressed as tau = 1.047 e(
      0.354x) and the rate constants of phosphorescence emission k(p) and non-radiation
      process k(i) from T1 --> S0 were 0.9551 s(-1) and 0.4276 s(-1) l(-1) mol,
      respectively.

PMID- 10907881
TI  - Ultraviolet absorption and vibrational spectra of 2-fluoro-5-bromopyridine.
AB  - The ultraviolet absorption spectrum in the range 340-185 nm in the vapour and
      solution phase has been measured for 2-fluoro-5-bromopyridine. Three fairly
      intense band systems identified as the pi* <-- pi transitions II, III and IV have
      been observed. A detailed vibronic analysis of the vapor and solution spectra is
      presented. The first system of bands is resolved into about sixty-two distinct
      vibronic bands in the vapour-phase spectrum. The 0,0 band is located at 35944 cm(
      1). Two well-developed progressions, in which the excited state frequencies nu'25
      (283 cm(-1)) and nu'19 (550 cm(-1)) are excited by several quanta, have been
      observed. The corresponding excited state vibrational and anharmonicity constants
      are found to be omega'i = 292 cm(-1), x'ii = 4.5 cm(-1) (i = 25) and omega'i =
      563.8 cm(-1), x'ii = 6.9 cm(-1) (i = 19). The other two band systems show no
      vibronic structure, the band maxima being located at 48346 and 52701 cm(-1),
      respectively. The oscillator strength of the band systems in different solutions
      and the excited state dipole moments associated with the first two transitions
      have been determined by the solvent-shift method. The infrared spectrum in the
      region 4000-130 cm(-1) and the laser Raman spectrum of the molecule in the liquid
      state have been measured and a complete vibrational assignment of the observed
      frequencies is given. A correlation of the ground and excited state fundamental
      frequencies observed in the UV absorption spectrum with the Raman or infrared
      frequencies is presented.

PMID- 10907882
TI  - Tautomers and conformers of malonamide, NH2-C(O)-CH2-C(O)-NH2: vibrational
      analysis, NMR spectra and ab initio calculations.
AB  - The conformational and tautomeric compositions of malonamide, NH2-C(O)-CH2-C(O)
      NH2 were determined by vibrational spectroscopy and theoretical calculations
      (HF/6-31G*, B3PW91/6-31G*). Solid state Fourier transform infrared and Raman
      spectra were analysed. They reveal the existence of a diketo tautomer.
      Theoretical calculations predict a diketo structure belonging to the C1 symmetry
      group. No enol form is present in the molecule in the solid. 13C-NMR studies show
      only signals of a diketo tautomer.

PMID- 10907884
TI  - Evidences for a localized chromophore in the Ti(IV)/squarate complex: a resonance
      Raman investigation.
AB  - The present work continues a previous investigation on the interaction of
      oxocarbonic anions with highly charged metal ions. When squarate or croconate
      solutions are added to Ti(IV) acidic solutions, a rather strong and broad band
      shows up that is not present in the optical spectrum of the reagents. Excitation
      of the Raman spectrum of the resulting coloured solutions close to their
      absorption maxima leads to the enhancement of several modes of the oxocarbon. In
      particular the totally symmetric nu(C=O) mode of the Ti(IV)/squarate or croconate
      complexes shows an outstanding enhancement, a completely different behaviour of
      that observed in the Raman spectrum of the free oxocarbons, where the nu(CO)
      modes are barely observed. Such result indicates a rather strong Ti(IV)-oxocarbon
      interaction via the CO moieties with the formation of a strongly allowed LMCT
      (ligand to metal charge transfer) state. In addition the rather selective
      enhancement of the nu(CO) modes strongly suggests that the chromophore involved
      in the LMCT state is highly localized in the Ti(IV)-CO moieties of the complexes
      and that the enhancement mechanism involved is very likely the one described by
      Albrecht's A term, i.e. Franck-Condon one state mechanism.

PMID- 10907883
TI  - A spectroscopic and magnetic study of complexes of bis(2-benzothiazolyl)methanate
      and bis(2-benzoxazolyl)methanate with Co(II), Ni(II), Cu(II) and Zn(II).
AB  - The co-ordination geometry of the complexes M(bbtm)2 and M(bbom)2 (M: Co, Ni, Cu,
      Zn; bbtm, bis(2-benzothiazolyl)methanate; bbom, bis(2-benzoxazolyl)methanate) are
      discussed on the basis of their IR, Raman, resonance Raman, electronic and ESR
      spectra. Compounds of Ni, Co, Zn with both ligands and Cu(bbom)2 resulted to have
      a distorted tetrahedral geometry. The distortion towards a square planar geometry
      is more marked for the M(bbtm)2 series than for the M(bbom)2 one. It has been
      impossible to suggest a co-ordination geometry for Cu(bbtm)2, that probably has a
      polymeric structure.

PMID- 10907885
TI  - Fourier transform infrared and Raman spectra of N-di-isopropylphosphorylguanidine
      (DPG).
AB  - The Fourier transform infrared and the Fourier transform Raman spectra of N-di
      isopropylphosphorylguanidine (DPG) in the solid state and in aqueous solution
      were recorded and analyzed. Assuming Cs symmetry for different structural
      fragment of the molecule, the experimental and calculated band assignments of the
      nu(NH), delta(HNH), delta(CNH), nu(C=N), nu(PN), nu(CN), nu(PO) and nu(OC) normal
      modes suggested that the DPG exists as a tautomeric contribution of the
      phosphorylamine (I) and N-phosphorylimine (II) structural forms. [structures: see
      text]

PMID- 10907886
TI  - Characterisation and theoretical investigation of the electronic properties and
      second-order nonlinearity of some three dentate salicylaldiminato Schiff base
      ligands.
AB  - A series of asymmetric three dentate salicylaldiminato Schiff base ligands 1-4
      (Scheme 1) has been synthesized and their structures, electronic properties and
      second order nonlinearities are investigated using the AM1 Hamiltonian SCF-MO
      methods. The analysis of MOs indicates that the O(2) atom could be the
      coordination site if the ligands were monodentate. In addition, the atomic
      orbitals on the O(9) atom have no contributions to the frontier MOs of the
      anionic form of these three dentate ligands. The Mulliken populations reveal that
      the coordination sites N(6) and O(9) possess different character in generation of
      the Schiff base complexes. The molecular first-order hyperpolarizability value of
      ligands was calculated using finite field method. Generally the presence of the
      methoxy group as third dentate play a major role in increasing the second
      harmonic generation (SHG) responses of three dentate ligands. Comparison of the
      NLO properties of two dentate with three dentate salicylaldiminine-based ligands
      reveals that the presence of -NO2 and -OCH3 groups as R1 and R2 substituents
      enhance the second-order nonlinear optic properties of these type ligands.

PMID- 10907887
TI  - Flow injection catalytic determination of ruthenium with spectrophotometric
      detection.
AB  - A new flow injection catalytic method was described for the determination of
      ruthenium(III) based on its catalytic effect on the oxidation of brilliant cresyl
      blue (BCB) by periodate in acidic media. The reaction was followed
      spectrophotometrically by measuring the absorbance of the dye at 635 nm. Under
      optimum conditions, ruthenium can be determined in the range of 1.0-100.0 ng ml(
      1) with a relative standard deviation of 1.1% and with a limit of detection of
      0.70 ng ml(-1). The influence of reagent and manifold variables were studied and
      optimized. The method was tested for the determination of ruthenium(III) in some
      synthetic mixtures.

PMID- 10907888
TI  - Raman study of molecular dynamics of inorganic fluoroxidizers in nonaqueous
      solutions: part 4. Xenon tetrafluoride and xenon hexafluoride in hydrogen
      fluoride.
AB  - Raman spectra of XeF4 and XeF6 in the nonaqueous HF solutions at various
      concentrations and vibrational spectra of the [XeF5]+ cation in the solid state
      and in the HF solutions over a wide range of vibrational frequencies have been
      studied. The assignments of the observed vibrational bands of the [XeF5]+ cation
      and XeF6-HF system has been made. A number of associates or solvates being formed
      as a result of the donor-acceptor interaction between Lewis base and Lewis acid
      has been shown to exist alongside with ionized monomeric and polymeric
      modifications of XeF6 in the HF solution such as ([XeF5]+ F-)n (n = 1, 2, 4). The
      contours of the nu1(A1g) band of XeF4 with frequency 552 cm(-1) and bands of
      stretching modes of ([XeF5]+ F-)n (n = 1, 2, 4) with frequency in the range of
      600-670 cm(-1) are analysed. The correlation functions of the vibrational and
      rotational relaxation as well as the corresponding characteristic time for these
      processes have been calculated. A conclusion has been driven at that it is
      vibrational dephasing that makes the major contribution to the formation of
      ([XeF5]+ F)4 and ([XeF5]+ F-)2 band contours, while in the case of [XeF5]+ F- and
      XeF4 the contributions of vibrational dephasing and rotational relaxation nearly
      coincide.

PMID- 10907889
TI  - Interatomic potentials of cadmium-argon B1(3sigma+) and X0+(1sigma+) states based
      on near-dissociation expansion and 'hot' bands observed in the B1 <-- X0+
      excitation spectrum.
AB  - B1(3sigma+) <-- X0+(1sigma+) excitation spectrum of the cadmium-argon van der
      Waals molecule has been recorded in the experiment of a continuous supersonic
      molecular beam crossed with a pulsed dye laser beam. The B1-state dissociation
      energy was directly observed and a long-range behavior of the B1-state
      intermolecular potential was derived using a near-dissociation expansion
      procedure of LeRoy and Bernstein. A first-time direct determination of the X0+
      ground state characteristics based on 'hot' bands observed is presented as well.
      The new result is compared with other experimental and theoretical reports
      available in the literature.

PMID- 10907890
TI  - Fourier transform infrared spectroscopic characterization of grafting of 3
      aminopropyl silanol onto aluminum/alumina substrate.
AB  - In order to remedy the limitations of state-of-the-art methods for red blood
      cells grouping and antibody screening we have tried to develop a new type of
      immunosensors based upon a metallic substrate. The first two steps of the
      manufacturing of such a sensor consist in the anodization and in the silanization
      of the metal surface. Fourier transform infrared spectroscopy (FTIR) has been
      used to investigate aluminum samples treated with the above process. FTIR
      analysis allows the accurate determination of the grafted species, and thus to
      perform the optimization of the experimental parameters.

PMID- 10907891
TI  - Investigation of the SERS behaviour of porphyrins with different surface
      concentrations on electrochemically prepared Ag-surface.
AB  - Surface-enhanced Raman scattering (SERS) spectra, taken with 632.8 nm excitation
      are reported for the water-soluble tetrakis(3-N-methylpyridyl)porphyrin chloride
      (TMPyP(3)), tetrakis(4-N-methylpyridyl)porphyrin chloride (TMPyP(4)) and
      Sn(IV)tetrakis(4-N-methylpyridyl)porphyrin chloride (Sn(IV)TMPyP(4)) using an
      electrochemically prepared Ag surface with an area ca. 12.56 mm2. It was found
      that the spectra vary as increasing amounts of the compounds are placed on the
      surface, with surface concentrations in the approximate range 1000-5 pmol/12.56
      mm2. We suggest that the reasons for the changes be that the reaction means
      between porphyrin molecules and Ag surface is different and the porphyrin
      macrocyclic molecules adopt different orientation as the surface concentrations
      decrease.

PMID- 10907892
TI  - A vibrational study of various K2PdCl(4-x)Br(x) solid solutions.
AB  - Infrared and Raman vibrational spectra (700-30 cm(-1)) have been recorded on
      various K2PdCl(4-x)Br(x) (0 < or = x < or = 4) powdered samples at 300 K,
      including both K2PdCl4 and K2PdBr4 compounds and ten solid solutions with a
      bromide content varying from 5-95%. Characteristic variations of the sectra
      clearly demonstrate a wide domain of existence of the solid solutions and the
      only possible additional existence, due to no IR-Raman coincidence, of the
      'trans' planar PdCl4Br2 centrosymmetric anion. A comparison of the vibrational
      data with results of valence force field calculations allows us to characterize
      this new anion, in Raman by two signals at 286 and 225 cm(-1) (v sym., Ag, PdCl2
      and PdBr2, respectively), in Infrared by not only the two bands at 309 and 200
      cm(-1) (v asym. B3u + B2u, of PdCl2 and PdBr2) but also intense deformation modes
      in the 178-140 cm(-1) wavenumber range. These results suggest slight
      modifications in the internal f(Pd-Cl) and f(Pd-Br) force constans on going from
      the PdCl4(2-) or PdBr4(2-) anions to the 'trans' PdCl2Br2(2-) anonic species.

PMID- 10907893
TI  - Spectroscopic properties and ligand field analysis of cis-diazido(1,4,8,11
      tetraazacyclotetradecane)chromium(III) azide.
AB  - The emission and excitation spectra of cis-[Cr(cyclam)(N3)2](N3) (cyclam =
      1,4,8,11-tetraazacyclotetradecane) taken at 77 K are reported. The infrared and
      visible spectra at room temperature are also measured. The vibrational intervals
      due to the electronic ground state are extracted from the far-infrared and
      emission spectra. The ten electronic bands due to spin-allowed and spin-forbidden
      transitions are assigned. Using the observed transitions, a ligand field analysis
      has been performed to determine the bonding property of azido group in the
      chromium(III) complex. It is found that azide ligand has weak sigma- and pi-donor
      properties toward chromium(III) ion. The zero-phonon line in the excitation
      spectrum splits into two components by 249 cm(-1), and the large 2Eg splitting
      can be reproduced by the ligand field theory.

PMID- 10907894
TI  - Intertester reliability of the McKenzie evaluation in assessing patients with
      mechanical low-back pain.
AB  - STUDY DESIGN: Prospective intertester reliability study investigating the ability
      of 2 therapists to agree on a low back pain diagnosis using examination
      techniques and the classification system described by McKenzie. OBJECTIVES: To
      investigate intertester agreement in determining McKenzie diagnostic syndromes,
      subsyndromes, presence, and relevance of the spinal deformities. BACKGROUND:
      Reliability of the McKenzie approach for determining diagnostic categories is
      unclear. Previous studies have been characterized by inconsistency of test
      protocols, criterion measures, and level of training of the examiners, which
      confounds the interpretation of results. METHODS: Patients were assessed
      simultaneously by 2 physical therapists trained in the McKenzie evaluation
      system. The therapists were randomly assigned as examiner and observer. Agreement
      was estimated by Kappa statistics. RESULTS: Forty-five subjects (47 +/- 14
      years), composed of 25 women and 20 men with acute, subacute, or chronic low back
      pain were examined. The agreement between raters for selection of the McKenzie
      syndromes was kappa = 0.70, and for the derangement subsyndromes was kappa =
      0.96. Interrater agreement for presence of lateral shift, relevance of lateral
      shift, relevance of lateral component, and deformity in sagittal plane was kappa
      = 0.52, 0.85, 0.95, and 1.00, respectively. Intertester agreement on syndrome
      categories in 17 patients under 55 years of age was excellent, with kapp = 1.00.
      CONCLUSIONS: A form of low back evaluation, using patterns of pain response to
      repeated end range spinal test movements, was highly reliable when performed by 2
      properly trained physical therapists.

PMID- 10907895
TI  - Electrothermally-assisted capsulorrhaphy (ETAC): a new surgical method for
      glenohumeral instability and its rehabilitation considerations.
AB  - Knowledge of current surgical procedures and the effect they have on healing
      tissue is important when developing rehabilitation guidelines. Recently,
      clinicians have been asked to treat patients who have undergone Electrothermally
      Assisted Capsulorrhaphy (ETAC) for shoulder instability. The ultimate tensile
      strength of the tightened capsule is unknown during various timeframes following
      surgery. The use of thermal energy to shrink the shoulder joint capsule initially
      causes weakness of the collagen ultrastructure. Rehabilitation following ETAC
      includes a period of relative immobilization, followed by controlled range of
      motion exercises. Exercises to strengthen shoulder muscles must be done in a
      manner that minimizes stress on the surgically treated capsule. This article
      provides a brief review of capsuloligamentous repair; describes the surgical
      procedure, its indications, contraindications, and the effect ETAC has on the
      healing tissue; and provides guidelines for rehabilitation following ETAC based
      on the evidence available and the authors clinical experience.

PMID- 10907896
TI  - Thoracic spine dysfunction in upper extremity complex regional pain syndrome type
      I.
AB  - STUDY DESIGN: Case study. OBJECTIVE: To demonstrate the importance of assessment
      and treatment of the thoracic spine in the management of a patient with signs and
      symptoms of upper extremity Complex Regional Pain Syndrome Type I (CRPS-I).
      BACKGROUND: The patient was a 38-year-old woman who suffered a traumatic injury
      to her left hand. Five months after injury, she presented with severe pain,
      immobility of the left arm, and associated dystrophic changes. She was unable to
      work and needed help in some activities of daily living. METHODS AND MEASURES:
      The patient was treated for 3 months in 36 visits. Initial treatment consisted of
      cutaneous desensitization, edema management, and gentle therapeutic exercises.
      However, further examination indicated hypomobility and hypersensitivity of the
      upper thoracic spine. Joint manipulation of the T3 and T4 segments was
      implemented. The patient's status was monitored and range of motion, strength,
      temperature, and skin moisture were measured. RESULTS: Immediately after the
      vertebral manipulation, there was a significant increase in the left hand's skin
      temperature and a decrease in hyperhydrosis as measured by palpation. Shoulder
      range of motion increased from 135-175 degrees and the patient reported reduced
      pain from 6/10 to 3/10 on a scale from 0 to 10, where 0 represents no pain. The
      decrease in the patient's dystrophic and allodynic symptoms permitted further
      progress in functional re-education. The patient was discharged with full return
      to independence and initiation of a vocational retraining program. CONCLUSION:
      Assessment and treatment of the thoracic spine should be considered in patients
      with upper extremity CRPS-I.

PMID- 10907897
TI  - Measurement of step widths and step lengths: a comparison of measurements made
      directly from a grid with those made from a video recording.

PMID- 10907898
TI  - Quadriceps and hamstrings peak torque ratio changes in persons with chronic
      anterior cruciate ligament deficiency.
AB  - STUDY DESIGN: Cross-sectional analytical study in which subjects served as their
      own controls. OBJECTIVE: To assess the concentric and eccentric peak torque in
      the hamstrings and quadriceps muscles, hamstrings/quadriceps amplitude ratios,
      and lean thigh volume differences in the involved and uninvolved limb of subjects
      with anterior cruciate ligament (ACL) deficiency. BACKGROUND: [corrected]
      Although the hamstrings/quadriceps ratios for concentric and eccentric activity
      have been studied, the more functional eccentric hamstings/concentric quadriceps
      ratio has not been previously described in chronic ACL deficient individuals.
      METHODS AND MEASURES: Eighteen subjects (36 +/- 11 years; 12 men, 6 women) with
      unilateral chronic ACL deficiency were recruited. Changes in activities of daily
      living, lean thigh volume (LTV) and isokinetic peak torque and total work
      capacity of both the quadriceps and hamstring muscles were investigated. The
      uninvolved limb served as control. RESULTS: Eccentric quadriceps peak torque in
      the ACL deficient limb was reduced by 38% compared with the 16% reduction of
      concentric quadriceps peak torque. Eccentric hamstrings peak torque was reduced
      by 15% compared with an 8% reduction in concentric hamstrings peak torque. LTV in
      the ACL deficient limb was 11% smaller than the uninvolved limb (3,541 +/- 899 vs
      3,161 +/- 742 cc, uninvolved versus ACL deficient limb). The relation between LTV
      and eccentric peak torque was stronger in the uninvolved (r = 0.82) compared with
      the ACL deficient limb (r = 0.66). The eccentric hamstrings/quadriceps ratio was
      significantly higher in the ACL deficient (0.80 +/- 0.26) compared with the
      uninvolved limb (0.55 +/- 0.13). However, the eccentric hamstrings/concentric
      quadriceps ratio was similar between ACL deficient (0.75 +/- 0.17) and uninvolved
      (0.77 +/- 0.20) limbs, while the concentric hamstrings/eccentric quadriceps ratio
      was significantly higher in the ACL deficient (0.79 +/- 0.26) compared with the
      uninvolved (0.50 +/- 0.14) limb. CONCLUSIONS: Quadriceps and hamstrings peak
      torque values were significantly decreased in ACL deficient compared with the
      uninvolved limb. Eccentric muscle activity was affected to a greater degree than
      concentric muscle activity in the quadriceps muscle after ACL injury. The
      eccentric hamstrings/concentric quadriceps ratios were similar in ACL deficient
      and normal limbs, indicating that muscular co-ordination strategies may have been
      altered to maintain normal limb activity despite the strength losses particularly
      evident in quadriceps muscle function.

PMID- 10907900
TI  - Revisting what is "evidence".

PMID- 10907899
TI  - Orthopaedic section responds to research isolationism.

PMID- 10907901
TI  - PNF and knee rehabilitation.

PMID- 10907902
TI  - Separation of church, state, and the Journal.

PMID- 10907903
TI  - Strategies for syphilis prevention: findings from surveys in a high-incidence
      area.
AB  - BACKGROUND: The persistence of syphilis in the United States suggests that a
      better understanding is needed of the potential for various public health
      approaches to prevent the spread of the disease. STUDY DESIGN: The authors
      conducted surveys of 92 persons with early syphilis, 56 uninfected sexual
      contacts, and 143 neighborhood controls in the Baton Rouge, Louisiana area. The
      surveys collected information regarding sexual behavior, access to and use of
      healthcare services, encounters at sites at which serologic screening for
      syphilis could be done, and exposure to interventions designed to prevent HIV
      infection. RESULTS: All groups reported high-risk sexual behavior. Cases and
      contacts were more likely than controls to report two or more sex partners in the
      previous year, but the three groups were similar in the percentage reporting five
      or more sex partners. Cases had poor access to health care and by some measures
      this access was less than that of controls. The potential screening site visited
      most frequently by cases was the public hospital emergency room (40%). Cases were
      less likely to have been exposed to programs designed to prevent HIV infection
      than uninfected contacts and controls combined (odds ratios, 0.51-0.66).
      CONCLUSIONS: Persons with syphilis were not unlike others in their neighborhoods,
      suggesting that syphilis is a sentinel event that indicates an entire
      neighborhood is at risk. Improvements in access to health care for sexually
      transmitted disease-related symptoms, screening in sites such as public hospital
      emergency rooms, and emphasizing sexual risk-reduction interventions may limit
      the spread of syphilis in these neighborhoods. To prevent syphilis in the long
      term, public health programs should also try to better understand and change
      other community-level socioeconomic factors that influence sexual behavior.

PMID- 10907904
TI  - Syphilis: a barometer of community health.

PMID- 10907905
TI  - Relationship of hormonal contraception and cervical ectopy as measured by
      computerized planimetry to chlamydial infection in adolescents.
AB  - BACKGROUND: Adolescents are at increased risk for chlamydial infection and its
      sequelae. Hormonal contraception and cervical ectopy were previously suggested
      risk factors for chlamydia. GOAL: To determine if chlamydia is more prevalent in
      female participants with greater ectopy and in hormonal contraceptive users.
      STUDY DESIGN: Ninety-seven adolescent females aged 11 to 20 years were recruited
      from two Baltimore inner-city clinics. After administering a reproductive history
      questionnaire, endocervical specimens were tested for Chlamydia trachomatis by
      polymerase chain reaction. After acetic acid application to the cervix, cervical
      photographs were taken, the area of ectopy was quantified by computerized
      planimetry, and ectopy was categorized as none (0mm2), mild (< 22mm2), and
      moderate (> 22mm2). The likelihood of chlamydia by ectopy and type of hormonal
      contraceptive use was determined by logistic regression adjusted for age and
      sexual partners. RESULTS: The odds of chlamydial infection was similar in persons
      with mild ectopy compared with no ectopy (adjusted odds ratio [OR], 0.76; 95% CI,
      0.14-4.03), and in persons with moderate ectopy compared with no ectopy (adjusted
      OR, 1.94; 95% CI, 0.40-9.39). The likelihood of chlamydia was higher in depot
      medroxyprogesterone acetate users compared with nonhormone users (adjusted OR,
      5.44; 95% CI, 1.25-23.6). Oral contraceptive users did not have an increased
      likelihood of chlamydia (adjusted OR, 0.92; 95% CI, 0.10-8.78). CONCLUSION: Using
      a new, reliable, and standardized technique to quantify cervical ectopy, the
      authors did not find an elevated prevalence of chlamydial infection in
      adolescents with cervical ectopy. Depot-medroxyprogesterone acetate use may
      increase the risk of chlamydial infection compared with combined estrogen
      progestin oral contraceptives.

PMID- 10907907
TI  - Behavioral aspects of sexually transmitted diseases: core groups and bridge
      populations.

PMID- 10907906
TI  - Sexual bridging by Cambodian men: potential importance for general population
      spread of STD and HIV epidemics.
AB  - BACKGROUND: Linkages between sexual networks influence STD and HIV epidemics.
      GOAL: This study quantifies male sexual "bridging" and associated factors in
      Cambodia's 1997 behavioral surveillance survey. STUDY DESIGN: Among persons
      randomly selected from clusters of military, police, and motorcycle taxidrivers
      in five cities, associations between individual characteristics, behaviors,
      social context, and "active bridging" were tested using logistic regression
      analyses. RESULTS: The authors defined 20.5%, 15.7%, and 14.7% of military,
      police, and motorcycle taxidrivers as active bridgers (men who have unprotected
      sex with high and low risk partners). Among the military and police, logistic
      regression revealed that age (odds ratio [OR], 1.05), age of first sexual
      intercourse (OR, 0.89), having friends who frequent sex workers (OR, 3.31), and
      residence in the port city (OR, 3.34) were associated with active bridging. Among
      motorcycle taxidrivers, residence in the border city (OR, 2.23) or the port city
      (OR, 2.84) was associated with active bridging. Sexually transmitted disease
      symptoms during the past year were significantly associated with active bridging.
      CONCLUSIONS: Social characteristics influence sexual bridging more than
      individual ones. The pervasiveness of bridging and the association with sexually
      transmitted disease symptoms underscore the potential of men who are active
      bridgers to spread sexually transmitted disease and HIV in Cambodia beyond high
      risk groups.

PMID- 10907908
TI  - Duration of untreated genital infections with chlamydia trachomatis: a review of
      the literature.
AB  - BACKGROUND: Estimates of the duration of untreated genital infections with
      Chlamydia trachomatis vary. Accurately estimating the distribution of the
      duration of infection would be useful in the counseling patients, and is
      essential when modeling the burden of chlamydial disease and the potential impact
      of prevention programs. GOAL: The authors review the scientific literature to
      summarize what is known about the duration of genital chlamydial infection and
      the factors that affect it. STUDY DESIGN: Literature review of animal and human
      studies. RESULTS: Animal studies document a longer duration of infection in
      primates than in mice or guinea pigs. Although animals spontaneously become
      culture negative over time, numerous studies document persistent nonculture
      evidence of chlamydiae in the upper genital tract. Studies in which women have
      been serially cultured suggest that most untreated infections remain culture
      positive for more than 60 days. Small series report that some infections may
      persist for years. Most infections eventually become culture negative; however,
      non-culture evidence of chlamydiae often persist in women with negative cultures.
      The duration of chlamydial infection is reduced in animals previously exposed to
      chlamydiae and in older humans, suggesting that partial immunity may result from
      exposure. Data are inadequate to define the median duration of untreated
      infection or to derive a curve that describes the natural history of untreated
      genital chlamydial infections. CONCLUSION: Current data do not allow one to
      reliably estimate the duration of genital infections with C trachomatis.
      Systematic retesting could help to better define the duration of infection in
      patients who, against medical advice, delay treatment for genital chlamydial
      infections.

PMID- 10907909
TI  - Heterosexual transmission of hepatitis C, hepatitis B, and HIV-1 in a sample of
      inner city women.
AB  - BACKGROUND: To clarify the role of heterosexual transmission of hepatitis C virus
      (HCV) and to identify associated risk factors. GOAL: To compare risk factors with
      infection among women with HCV, HIV-1, and hepatitis B virus (HBV). STUDY DESIGN:
      A cross-sectional study of the prevalence of HCV, HIV-1, and HBV in a sample of
      599 sexually active, nontransfused, inner-city women with no evidence of
      intravenous drug use. RESULTS: The prevalence of HCV was 1.6%, compared with 2.0%
      for HIV-1 and 18.8% for HBV; 75% of women infected with HCV were also infected
      with HIV-1 or HBV (P < 0.001). Women engaging in very high-risk sexual behavior
      were 14.2 times more likely to have HCV than other women (95% CI, 1.8-642.5).
      CONCLUSIONS: The epidemic of HCV may be facilitated by high-risk sexual behavior.
      The relatively high prevalence of HCV suggests the need for more widespread
      screening among inner-city females.

PMID- 10907910
TI  - Sexually transmitted disease clinic clients at risk for subsequent gonorrhea and
      chlamydia infections: possible 'core' transmitters.
AB  - BACKGROUND: From an sexually transmitted disease (STD) intervention perspective,
      developing a practical way to identify persons in core transmitter groups has
      been difficult. However, persons who have repeated STD infections may be in such
      groups. GOAL: To evaluate a self-administered risk assessment approach that would
      identify STD clinic clients who were at an increased risk of being involved in
      gonorrhea (GC) or chlamydia (CT) transmission in the subsequent year. STUDY
      DESIGN: Prospective cohort of consecutive STD clinic clients with a 1-year follow
      up period. RESULTS: During a 6-month period in 1995, 2576 STD clinic clients in
      San Diego completed a risk assessment. Of those clients, 204 (7.9%) had a
      subsequent STD and 79 (3.1%) had a subsequent GC or CT infection during the 1
      year follow-up period. The strongest predictor of a subsequent GC/CT was having a
      recent history or current clinic visit diagnosis of GC or CT (6.1% subsequent
      GC/CT rate). The more past episodes of GC or CT, the higher the subsequent GC/CT
      rate. Unsafe sexual behavior had little effect on further increasing subsequent
      GC/CT risk. CONCLUSION: STD clinic clients with a recent history of GC or CT and
      a high risk of subsequent GC/CT may be core transmitters who could likely benefit
      from risk reduction, periodic screening for GC/CT, symptom recognition
      counseling, and preventive treatment-the essential elements of STD-prevention
      case management.

PMID- 10907911
TI  - Recidivism redux.

PMID- 10907912
TI  - Availability of condoms in urban and rural areas of KwaZulu-Natal, South Africa.
AB  - BACKGROUND: Promoting condom use to prevent HIV transmission is futile if condoms
      are not readily available. GOAL: This study assessed condom availability in
      clinics, shops, and other outlets in urban and rural South Africa. STUDY DESIGN:
      Snowball sampling was used to select 70 private-sector and public-sector outlets.
      One male and one female black fieldworker were posed as clients seeking condoms
      to assess condom availability and provider attitudes. RESULTS: Condoms were
      available in nine (100%) public clinics, in five of nine (55%) private doctor's
      rooms, and in only 5 of 52 (10%) nonhealth outlets. Access was limited in the
      public sector by clinic opening times, inadequate clinic signs and markings, and
      by some providers' attitudes. CONCLUSION: A major opportunity to make condoms
      available in nonhealth outlets in rural areas and urban townships is being missed
      in South Africa. Above all, the high level of condom awareness is not being
      matched by easy availability.

PMID- 10907913
TI  - Prevalence of sexually transmitted infections among clients of female commercial
      sex workers in Thailand.
AB  - BACKGROUND: Clients of commercial sex workers are considered at high risk for the
      acquisition and transmission of sexually transmitted diseases (STDs).
      Identification and treatment of infections in this group could help to reduce the
      transmission of STDs. GOAL: To ascertain the prevalence of sexually transmitted
      organisms in male clients of female sex workers in Thailand by analysis of
      seminal fluid collected after intercourse. STUDY DESIGN: Used condoms were
      collected from 291 male clients attending a brothel in Hat Yai, Thailand during a
      7-day period. Nucleic acid was extracted from seminal fluid and tested by
      polymerase chain reaction for the presence of Chlamydia trachomatis, Neisseria
      gonorrhoeae, Trichomonas vaginalis, herpes simplex virus (HSV) and HIV sequences.
      RESULTS: Overall, 17 (6%), 47 (16%), and 2 (1%) of specimens were positive for C
      trachomatis, N gonorrhoeae and T vaginalis respectively. HSV sequences were found
      in 24 (8%) of the specimens: 14 specimens (5%) with HSV type 1, and 11 specimens
      (4%) with HSV type 2. HIV RNA was detected in two samples (1%). Overall, 75
      specimens (26%) were positive for one or more infections, and more than one
      pathogen was detected in 16 specimens (5%). CONCLUSION: This study reports a high
      rate of STDs among clients of female sex workers in Thailand. Consequently, this
      population is a significant risk for transmitting STDs to commercial sex workers
      and to other noncommercial partners. Strategies that target this population of
      men are needed to reduce STD and HIV transmission.

PMID- 10907914
TI  - Adrenoleukodystrophy.

PMID- 10907915
TI  - Selection of viable sperm from frozen-thawed immotile spermatozoa based on the
      phenomenon of sperm tail curling in men who underwent testicular biopsy and
      epididymal sperm aspiration.

PMID- 10907916
TI  - In situ use of pentoxifylline to assess sperm vitality in intracytoplasmic sperm
      injection for treatment of patients with total lack of sperm movement.

PMID- 10907917
TI  - Do assisted reproductive technologies have effects on the demography of
      monozygotic twinning?

PMID- 10907918
TI  - Clinical studies without patients.

PMID- 10907919
TI  - Clinical studies without patients.

PMID- 10907920
TI  - Clinical studies without patients.

PMID- 10907921
TI  - Irreproducible results: good for surgeons, bad for scientists.

PMID- 10907922
TI  - Irreproducible results: good for surgeons, bad for scientists.

PMID- 10907923
TI  - Thin-layer technology: tempered enthusiasm.
AB  - With the introduction of new technologies we often see a pattern of development.
      As a useful technology moves into the public sector there is often an episode of
      wild enthusiasm and uncritical acceptance, followed by a time of progressive
      disillusionment. However, with time and experience, a proper place for the method
      becomes established. Thin-layer technology is certainly an improvement and solves
      many of our preanalytical problems; however, it introduces some difficulties of
      its own. The rounding up of cells in liquid fixation makes cells of high-grade
      lesions smaller than they would be on a conventional preparation. The abnormal
      cells are often separated. For both of these reasons they may be overlooked.
      Furthermore, benign glandular cells can take on an ominous appearance. These
      differences in conventional and thin-layer morphology are proving to be a
      fruitful area for publication. Thin-layer technology cannot be all things to all
      situations, and this is especially true in body fluid and fine-needle
      cytomorphology. In our experience, while occasionally helpful, the thin-layer
      technique should not be the primary method for diagnosis in nongynecologic
      specimens. Time and effort would be better spent on trying to educate select
      clinicians on how to obtain better samples than to totally convert to thin-layer
      methodologies. Regarding FNA, the patient is best served when the pathologist is
      directly involved with the initial sample acquisition. Reimbursement is available
      for immediate sample interpretation, so funding should be available for staffing
      if an institution has the interest. For the record, we believe that liquid
      fixation and thin-layer methodology should not be the primary method for FNA,
      unless circumstances are absolutely prohibitive. An important problem with thin
      layer technology lies with its added cost. Thin-layer interposes another series
      of steps into cytologic sample preparation. There is additional labor, additional
      time, another machine in the laboratory, and the significant cost of the
      reagents. In a situation where the price of a cytologic test is already close to
      margin, costs of the vial, filter, and preservative throw the test into
      unprofitability. Price structures have to be changed. Some institutions are
      waiting until there is more competition in the market and costs decrease.
      Alternatively, a lot of effort has been expended in trying to get government and
      other groups to accept the additional costs of the new test for gynecologic
      examinations, and many payers seem to be falling in line to accept the
      methodology, secondary to clinician and patient demand. Basic questions about
      ancillary technologies and gynecologic samples remain to be answered. Cytology is
      big business. Every year a significant segment of the population has a Pap smear
      performed. Hardly any other laboratory test can claim the volume of activity of
      the cervical smear. Any business that can hook into that market stands to
      prosper. Since the Pap smear has some well-publicized problems, the door is open
      for technology to nibble away at a few percentage points of false negativity. We
      are far from the first to ask if we can afford the incremental improvements of
      thin-layer and other ancillary technologies. There is a conundrum. Government,
      insurance companies, and our administrators are calling for us to hold back cost
      increases in medical care. Alternatively, these new technologies, patient demand
      for the perfect test, increased regulatory oversight, and legal challenges are
      increasing the cost of doing business. We do not know how to respond to the often
      voiced fear that these ancillary technologies increase the cost of cytology
      services beyond some patients' ability to pay. In this confusion, we do know that
      we should use the best test to get the most accurate answer for our patients. In
      selected scenarios this may mean that we will have to accept the cost and follow
      thin-layer technology.

PMID- 10907925
TI  - Exfoliative cytology of primary poorly differentiated (small-cell) neuroendocrine
      carcinoma of the uterine cervix in ThinPrep material: a case report.
AB  - Poorly differentiated neuroendocrine (small-cell) carcinoma of cervical origin is
      a rare neoplasm that frequently metastasizes. Although the cytologic features
      have been described for conventional cervical smears, we know of no reports of
      its appearance in ThinPrep (TP) material. Therefore, we present a TP case of
      primary, small-cell carcinoma arising in a 46-yr-old female, confirmed by
      histologic and immunohistochemical analysis. Similar to conventional smears, the
      neoplastic cells occurred either individually or in small clusters. The cells
      were relatively monomorphic, with stippled chromatin and minimal amounts of
      cytoplasm. Unlike conventional smears, nuclear molding was not prominent
      (although overlap was observed), and nuclear smearing was not identified. The
      features are compared to TP cases of squamous-cell carcinoma, small-cell type,
      and endometrioid adenocarcinoma, which are close mimics of small-cell carcinoma.
      We conclude that correct diagnosis of small-cell carcinoma in TP is difficult,
      requiring a high degree of suspicion and immunohistochemical confirmation.

PMID- 10907924
TI  - Interpretation of fine-needle aspirates processed by the ThinPrep technique:
      cytologic artifacts and diagnostic pitfalls.
AB  - The improvement in quality of cytologic preparations with the use of the ThinPrep
      methodology has been well-documented, but the cytologic artifacts resulting from
      this technique have not been adequately described. This study describes and
      illustrates the cytologic artifacts introduced by the ThinPrep technique when
      used on fine-needle aspirates (FNAs), and evaluates these artifacts as potential
      diagnostic pitfalls. We reviewed a total of 120 FNAs simultaneously processed by
      both conventional smears and ThinPrep. FNAs were obtained from the following
      sites: lymph node (27), breast (23), soft-tissue sites (20), salivary glands
      (13), gastrointestinal tract (10), lung (9), thyroid gland (13), liver (3),
      adrenal gland (1), and kidney (1). The ThinPrep smears were consistently devoid
      of obscuring elements, and the cells were adequately preserved and evenly
      dispersed. However, we noted some cytomorphologic alterations that should be
      recognized to avoid erroneous diagnoses. The size of cell clusters was decreased,
      large branching sheets were fragmented, and there were more single cells,
      resulting in apparent discohesion. Small cells such as lymphocytes tended to
      aggregate. All cells were generally smaller and occasionally spindled, the
      chromatin detail was attenuated, and nucleoli were more prominent. Intranuclear
      inclusions were difficult to visualize. Background matrix was often altered in
      both quantity and quality. Extracellular particles, small mononuclear cells, red
      blood cells, and myoepithelial cells were markedly decreased in number. The
      pathologist should be cautious in interpreting FNAs prepared using ThinPrep if
      that is the only methodology employed. Familiarity with artifacts is essential to
      avoid misinterpretations.

PMID- 10907926
TI  - ThinPrep Pap Test promotes detection of glandular lesions of the endocervix.
AB  - The objectives of this study were to evaluate 1) the detection rate of atypical
      glandular cells of undetermined significance of endocervical cell type (AGUS-EC)
      and 2) the correlation between AGUS-EC on cytology and biopsy results using the
      conventional Papanicolaou (Pap) smear test vs. the ThinPrep Pap test (TPPT).
      Cervical-vaginal samples processed by the conventional Pap smear for 11 mo in
      1996-1997 were identified, as were TPPTs collected for the same interval in 1997
      1998. Biopsy results were compared after a 9-mo follow-up for both groups. There
      were 112 AGUS-EC cases from 82,754 conventional Pap smears (detection rate,
      0.14%) compared with 58 cases from 82,252 TPPTs (detection rate, 0.07%) (P <
      0.01). Biopsies were available in 72 of 112 patients from the conventional Pap
      smear group and 35 of 58 patients from the TPPT groups. Five dysplastic glandular
      lesions/ AIS were diagnosed by biopsy in the 35 patients (14.3%)from the TPPT
      group, compared with 2 of the 72 patients (2.8%) from the conventional Pap smear
      group (P < 0.05). There were no statistically significant differences between
      other follow-up diagnoses for the two methods. The use of TPPT resulted in fewer
      cases of AGUS-EC and better correlation with histology. The TPPT appears to be as
      sensitive as and more specific than the conventional Pap smear for detection of
      endocervical glandular lesions.

PMID- 10907927
TI  - Specimen adequacy and the ThinPrep Pap Test: the endocervical component.
AB  - The ThinPrep Pap Test (Cyryc Corp., Boxborough, MA) has proven to be effective in
      decreasing the number of cervical specimens limited for interpretation by
      blood/inflammatory exudate as compared to conventional smears. However, its
      effectiveness in decreasing the number of preparations which lack an endocervical
      component is less well-established. The purpose of this 1-yr study (January 1998
      December 1998) was to determine if the collecting instruments used by physicians
      played a role in the lack of an endocervical component on ThinPrep slides. On
      implementation of the ThinPrep Pap Test for cervical cytology, the broom-type
      sampling device (Papette, Wallach Surgical Devices, Inc., Millford, CT) was the
      FDA-approved collecting instrument. Subsequently the combined plastic
      spatula/Zelsmyr Cytobrush (Medscand, Inc., Hollywood, FL) were approved. A survey
      was sent to 102 physicians in seven primarY care sites and two private obstetrics
      gynecology practices affiliated with the Loyola University Health Care System.
      One site used the broom only, one site used the spatula/cytobrush, five sites
      used the broom/cytobrush, and in two sites, two different sets of collecting
      instruments were utilized. Of the 10,241 ThinPrep samples, 620 (6%) were obtained
      with the broom only, 432 (4.3%) with the spatula/cytobrush, and 9,189 (89.7%)
      with the broom/cytobrush. An endocervical component was absent in 24% (range,
      13.7-25%) of the cervical samples collected with the broom only, 10% (range, 8.4
      12.5%) with the spatula/cytobrush, and 13% (range, 6.2-18.8%) with the broom/
      cytobrush. The spatula/cytobrush and the broom/cytobrush showed statistical
      significance (P < 0.001) over the broom alone in the collection of an
      endocervical component. The results of this study indicate that the collecting
      instruments used by the physician(s) played a role in the adequacy (endocervical
      component) of the specimen processed by the ThinPrep method. Diagn. Cyto

PMID- 10907928
TI  - Use of ThinPrep processing for studying breast cancer cell lines.

PMID- 10907929
TI  - Accuracy of cytologic diagnoses made from touch imprints of image-guided needle
      biopsy specimens of nonpalpable breast abnormalities.
AB  - We investigated the diagnostic utility and accuracy of touch imprints (TIs)
      prepared from core-needle biopsy (CNB) specimens of nonpalpable breast
      abnormalities. We reviewed air-dried, Diff-Quik-stained TIs prepared from 172
      consecutive CNB specimens obtained with stereotactic or sonographic guidance.
      Using criteria established for fine-needle aspirates, TIs were categorized as
      benign, atypical, suspicious, malignant, or unsatisfactory (i.e., showing fewer
      than six benign epithelial cell clusters or cell distortion). Cytologic diagnoses
      of TIs were then correlated with the histologic diagnoses of corresponding CNB
      specimens. CNB specimens were histologically diagnosed as carcinoma (102 cases),
      benign (59 cases), low-grade phyllode tumor (six cases), and atypical ductal
      hyperplasia (five cases). TIs were cytologically diagnosed as malignant (63
      cases), benign (35 cases), suspicious (19 cases), atypical (18 cases), and
      unsatisfactory (37 cases). Correlation of the cytologic and histologic diagnoses
      showed that five TIs diagnosed as benign were false-negative results for
      histologically diagnosed carcinomas (four cases) and phyllodes tumor (one case).
      False-negative results were attributed to poor representation of malignant cells.
      Two TIs diagnosed as suspicious were false results for two histologically
      diagnosed fibroadenomas. The false suspicious findings resulted from TIs with
      high cellularity, cytologic atypia, or no familiar (i.e., as seen on fine-needle
      aspirates) smear pattern. Unsatisfactory TIs were noted in both benign (44%) and
      malignant (11%) CNB specimens. When lesions categorized as suspicious were
      grouped with the malignant cases and those classified as atypical were grouped
      with the negative cases, TI sensitivity and specificity, were 83% and 95%,
      respectively. Fibroadenomas are difficult to identify on TIs and are likely to be
      misdiagnosed as suspicious. While high- and intermediate-grade carcinomas are
      easily categorized using TIs, low-grade carcinomas are best categorized as
      suspicious because of overlapping cytologic features with proliferative breast
      lesions. Increased experience with cytologic analysis of TIs improves the
      accuracy of cytologic diagnoses.

PMID- 10907930
TI  - Fine-needle aspiration of scalp lesions.
AB  - A variety of inflammatory and neoplastic scalp lesions are encountered in
      surgical pathology. However, the literature on fine-needle aspirations (FNAs) of
      the scalp is exceedingly rare. We report on a series of 70 FNAs involving
      cutaneous and subcutaneous lesions on the scalp. A total of 70 fine-needle
      aspirations of cutaneous and subcutaneous scalp lesions was reviewed to identify
      patterns of metastasis to the scalp and to demonstrate the effectiveness of FNA
      in diagnosing these lesions. There were 42 male and 28 female patients, ranging
      in age from 29-91 yr (mean, approximately 61 yr). Sixty-one patients had a
      previous history of malignancy. Of these aspirates, 59 were neoplastic,
      consistent with the patient's known primary. One case was an abscess, and the
      remaining case was unsatisfactorvy for cytologic evaluation. Follow-up biopsy
      revealed granulomatous inflammation. The most common primary tumor to metastasize
      to the scalp was lung carcinoma, which was seen in 18 cases, followed by
      hematopoietic malignancies in 14 cases. Melanoma was identified in 6 cases, head
      and neck tumors in 5 cases, renal malignancies in 4 cases, gastrointestinal
      tumors in 3 cases, sarcoma in 3 cases, breast and prostate malignancy in 2 cases
      each, and an olfactory neuroblastoma and meningioma in 1 case each. The remaining
      9 aspirates were from patients who did not have a previous history of malignancy.
      These included 6 benign aspirates consisting of 3 epidermal inclusion cysts, 2
      lipomas, and 1 neurofibroma. Two aspirates were malignant and included 1 primary
      squamous-cell carcinoma and 1 metastatic adenocarcinoma of unknown origin. The
      remaining case was unsatisfactory for cytologic evaluation. Follow-up biopsy of
      this lesion showed noncaseating granulomas. Of the aspirates from patients with a
      previous history of malignancy, 97% were neoplastic. Lung carcinoma and
      hematopoietic malignancies were the most common neoplasms that metastasized to
      the scalp. Since the scalp is a common site for metastasis, awareness of this
      fact is useful to both oncologists and dermatologists. It must be understood that
      FNA can provide a rapid and accurate diagnosis in the evaluation of scalp masses.

PMID- 10907931
TI  - Fine-needle aspiration of breast carcinomas with prominent lymphocytic
      infiltrate.
AB  - Carcinomas of the breast with prominent lymphoplasmacytic background are commonly
      encountered in cytology. The aim of this study was to assess the prevalence of
      different types of carcinomas that share this common feature, identify possible
      distinguishing cytologic features, and evaluate the diagnostic pitfalls in this
      group of tumors. Eighteen fine-needle aspirations (FNAs) of breast carcinomas
      with heavy lymphoplasmacytic background were reviewed. Histologic follow-up was
      reviewed in all cases. Of 18 cases, there were 9 invasive ductal carcinomas
      (IDC), and 9 medullary carcinomas (6 typical and 3 atypical). FNAs from typical
      medullary carcinomas (TMC) showed more severe nuclear atypia and macronucleoli
      than the cases of IDC and atypical medullary carcinomas (AMC). Gland formation
      was absent in the TMC but was common in IDC and AMC. No cytologic differences
      were noted between IDC and AMC. Nucleoli were larger in TMC (mean 4, microm) than
      in AMC (mean, 2 microm) and IDC (mean, 1.5 microm). We conclude that lymphocytes
      and plasma cells may be seen in different types of breast carcinomas and should
      not be considered a diagnostic feature of TMC. Features potentially helpful in
      the cytologic differential diagnosis of a carcinoma with prominent
      lymphoplasmacytic background are nucleolar size (4 microm in MC, vs. 1.5 and 2
      microm in IDC and AMC, respectively) and the degree of nuclear atypia.
      Lymphocytosis may be part of the carcinoma or may originate from a lymph node
      involved by metastases. In rare cases, a prominent neutrophilic infiltrate may
      also be present.

PMID- 10907932
TI  - Extracranial metastasis of a glioma: diagnosis by fine-needle aspiration and
      immunocytochemistry.
AB  - Fine-needle aspiration cytology (FNAC) is a well-established method for the rapid
      diagnosis of metastatic neoplasms. A case of metastatic glioma to the neck is
      presented. Diagnosis was made by FNAC combined with immunocytological techniques
      (glial fibrillary acidic protein). To the best of our knowledge, there have only
      been six previous cases of metastatic gliomas diagnosed by FNAC. FNAC, combined
      with clinical history and immunocytochemistry, is a rapid and reliable method in
      the definitive diagnosis of metastatic gliomas.

PMID- 10907933
TI  - Fine-needle aspiration of a metaplastic breast carcinoma with extensive
      melanocytic differentiation: a case report.
AB  - Metaplastic carcinomas of the breast are uncommon breast tumors with aberrant
      cellular differentiation, most commonly showing ductal, squamous, and mesenchymal
      components. A breast carcinoma composed of both epithelial and melanocytic
      differentiation is rare, with only four previously reported cases in the
      literature. We present the fifth reported case, where the diagnosis was suggested
      by fine-needle aspiration (FNA) and later confirmed after the surgical specimen
      was excised. Histologically, this neoplasm revealed multidirectional
      differentiation, consisting primarily of squamous and melanocytic cell types,
      with focal glandular and osseous metaplasia. Based on the morphologic,
      immunohistochemical, and ultrastructural findings, we conclude that such tumors
      fall within the spectrum of metaplastic carcinomas of the breast. We believe that
      this case will further contribute to the understanding of this enigmatic tumor.

PMID- 10907934
TI  - Gastric zygomycosis diagnosed by brushing cytology.
AB  - A 66-yr-old man with a history of squamous cell carcinoma and small cell
      carcinoma of the lung presented with nausea, vomiting, and abdominal pain. After
      passing black stools, he underwent upper endoscopy which showed gastric
      ulceration. A gastric brushing was performed which showed numerous nonseptate,
      ribbon-like hyphae with right-angle branching. The cytologic features permitted a
      diagnosis of a zygomycotic infection which was confirmed by histologic
      examination. Despite appropriate antifungal therapy, the patient expired. To the
      best of our knowledge, this is the first case of gastric zygomycosis diagnosed by
      brushing cytology. We believe that gastric brushing cytology allows for rapid
      diagnosis of zygomycotic mycoses, due to the distinctive morphology of these
      organisms; however, histologic examination is still required for assessment of
      invasion.

PMID- 10907935
TI  - Fine-needle aspiration diagnosis of psammomatous melanotic schwannoma.
AB  - A 51-yr-old male presented with an 8-mo history of lower back pain. Computerized
      axial tomography (CT) and magnetic resonance imaging (MRI) studies showed a 3.5 X
      3.0 cm sacral mass within the spinal canal in the region of the left S2 nerve
      root. A fine-needle aspirate biopsy (FNAB) was performed under CT guidance. The
      cytologic findings included a spindle-cell population with a fibrillary
      background arranged in a vaguely streaming pattern, wavy nuclei with mild atypia,
      wispy cytoplasm, rare intranuclear inclusions, and dilated vascular spaces. Some
      cells contained a nonrefractile granular brown pigment consistent with melanin.
      Also identified were calcified concentric laminations typical of psammoma bodies.
      Immunohistochemically, the neoplastic cells were strongly immunoreactive for S
      100 protein and HMB-45. A diagnosis of psammomatous melanotic schwannoma was
      rendered. No stigmata of Carney's complex were identified on physical
      examination. The patient has declined the recommendation of surgical excision of
      the mass. We herein describe a case unequivocally diagnosed as psammomatous
      melanotic schwannoma by FNAB.

PMID- 10907936
TI  - Fine-needle aspiration cytology: a survey of current utilization in relationship
      to hospital size, surgical pathology volume, and institution type.
AB  - Fine-needle aspiration cytology has become an accepted technique for the
      preoperative diagnosis of palpable and radiographically detected lesions at a
      wide variety of body sites. Little information exists regarding the degree of
      utilization of the technique in the general medical community. The present study
      investigated the number of fine-needle aspirations (FNAs) performed in
      relationship to hospital size, surgical pathology caseload, and type of hospital.
      Six hospitals from each state were selected at random (total of 300), and a
      survey was sent which requested the following information: hospital size,
      surgical pathology caseload, FNA volume, most common sites aspirated, change in
      FNA utilization over the last 5 years, and who was performing the needle
      aspirates. Usable responses were received from 133 institutions. The survey
      revealed that in 63% of institutions, FNAs were performed predominantly or
      exclusively by clinicians. An increase in number of FNAs performed was reported
      in 73% of institutions, while 11% reported a net decrease in FNA volume. The
      breast was the most common organ undergoing needle aspiration, followed by the
      thyroid and lung. For all hospitals, irrespective of size and type, FNA volume
      represented about 2.5% of the total surgical pathology volume. For nonacademic
      tertiary-care institutions, FNA represented approximately 1.2% of the surgical
      pathology caseload, and for academic tertiary-care institutions, FNA volume was
      approximately 3.6% of cases. The survey indicated that utilization of FNA
      continues to increase, is predominantly performed by clinicians, and represents a
      greater percentage of tissue examinations in academic tertiary-care institutions
      than in either community general hospitals or nonacademic tertiary-care
      institutions.

PMID- 10907937
TI  - Evaluation methods for assessing cytotechnology students' screening skills.
AB  - The development of slide screening skills to achieve diagnostic accuracy is the
      goal of cytotechnology education. There is limited time in the typical
      cytotechnology training program in which to acquire the didactic knowledge as
      well as screening experience. It is easier to teach the morphologic criteria
      necessary to refine diagnostic skills, but more difficult to teach and acquire
      locator skills. A survey was conducted to document and assess methods of
      evaluating screening skills utilized by U.S. cytotechnology educational programs.
      Graduation requirements and grading methods related to slide screening volume and
      accuracy were provided by survey participants. Current methods are varied, but
      appear to be effective in assessing diagnostic accuracy and graduate competence.
      A considerable period of time is required for students to gain enough screening
      experience to perform at required levels of volume and accuracy.

PMID- 10907938
TI  - Cytopathology in Sweden.

PMID- 10907939
TI  - Plasma D-dimer levels in elderly patients with suspected pulmonary embolism.

PMID- 10907940
TI  - Tamoxifen for early breast cancer: better late than never.

PMID- 10907941
TI  - Grading of chemotherapy-induced peripheral neuropathy.

PMID- 10907942
TI  - Delayed adjuvant tamoxifen: ten-year results of a collaborative randomized
      controlled trial in early breast cancer (TAM-02 trial)
AB  - AIM: Immediate adjuvant tamoxifen reduces disease recurrence and improves
      survival in patients with early breast cancer. However, is it too late to
      administer tamoxifen to patients who have already undergone treatment, but were
      unable to benefit from this adjuvant therapy? The French National Cancer Centers
      (FNCLCC) have investigated the efficacy of delayed tamoxifen administration in a
      randomized controlled trial. PATIENTS AND METHODS: From September 1986 to October
      1989, women with primary breast cancer, who had undergone surgery, radiotherapy,
      and/or received adjuvant chemotherapy but not hormone therapy more than two years
      earlier, were randomized to receive either 30 mg/day tamoxifen or no treatment.
      The 10-year disease-free and overall survival rates of the two groups of patients
      and of various subgroups were determined according to the Kaplan-Meyer method and
      compared by the log-rank test. RESULTS: This intention-to-treat analysis
      comprised 250 Introduction women in the tamoxifen group and 244 in the control
      group. Patient characteristics (age, T stage, number of positive nodes, receptor
      status, and interval since tumor treatment) were comparable in both groups.
      Delayed adjuvant tamoxifen significantly improved overall survival only in node
      positive patients and in patients with estrogen receptor-positive (ER+) or
      progesterone receptor-positive (PR+) tumors. Disease-free survival, however, was
      significantly improved in the global population and in several patient subgroups
      (node-positive, ER+, PR+). Patients in whom the interval between primary
      treatment and delayed adjuvant tamoxifen was greater than five years also had
      significantly improved disease-free survival. CONCLUSIONS: Overall and disease
      free survival results indicate that delayed adjuvant tamoxifen administration (30
      mg/day) is justified in women with early breast cancer, even if this treatment is
      initiated two or more years after primary treatment.

PMID- 10907943
TI  - The product of the t(11;18), an API2-MLT fusion, is an almost exclusive finding
      in marginal zone cell lymphoma of extranodal MALT-type.
AB  - BACKGROUND: Extranodal marginal zone cell lymphoma (MZCL) of MALT-type share
      similar features with nodal and splenic MZCL regarding morphology and
      immunophenotype. At the genetic level, recent cytogenetic studies have shown that
      t(11;18) is a recurring abnormality in extranodal MALT-type MZCL but has hitherto
      never been reported in nodal or splenic MZCL. The aim of the present study was to
      determine the prevalence of t(11;18) in a large series of nodal, splenic and
      extranodal MALT-type MZCL, using a sensitive real-time RT-PCR method. MATERIALS
      AND METHODS: Ninety-three MZCL cases were divided on clinical grounds into 61
      extranodal MALT-type, 19 splenic and 12 nodal MZCL. One case that presented with
      a massive splenomegaly but for which also gastro-intestinal localisations were
      found, was left unclassified. A real-time RT-PCR method for the detection of the
      API2-MLT fusion resulting from t(11;18) was performed on RNA extracted from
      frozen tissue sections. RESULTS: The API2-MLT fusion was detected in 12 cases,
      which were all extranodal MALT-type lymphomas of the stomach, except for one
      case. The remaining positive case was the unclassified case, for which the
      translocation was detected in the spleen and in hilar lymph node tissue.
      CONCLUSIONS: While similarities between MZCL from different anatomic sites have
      lend us to propose that all MZCL have a common normal counterpart, the almost
      exclusive detection of t(11;18) in gastric MALT-type lymphoma favours its
      recognition as a separate lymphoma entity. The absence of the translocation in
      nodal and splenic MZCL challenges the idea of these lymphomas being secondary to
      MALT-type lymphomas of the gut. The unclassified case illustrates the inadequate
      approaches available at present to identify and define the various MZCL.

PMID- 10907944
TI  - Long-term follow-up and residual sequelae after treatment for intracerebral germ
      cell tumour in children and adolescents.
AB  - BACKGROUND: Information on long-term follow-up of children and adolescents
      treated for intracerebral germ-cell tumour is scant. We report on the results of
      a small series of patients treated at a single institution. PATIENTS AND METHODS:
      Hospital records from 15 patients treated between 1980 and 1998 were reviewed. An
      attempt was made to correlate sequelae to tumour location and treatment
      modalities. RESULTS: This cohort constitutes 5.5% of all brain tumours diagnosed
      at our institution. HISTOLOGY: 10 germinomas, 2 benign teratomas, 2 malignant
      teratomas, and one mixed germ-cell tumour. Overall survival was 87%, with a mean
      follow-up time of 7 years and 8 months. The majority of patients have long-term
      sequelae involving one or several organ systems. In 66% endocrine, in 47%
      ophthalmologic, in 60% neuropsychological defects were observed. Endocrine and
      ophthalmologic sequelae show a correlation to tumour location. Neuropsychological
      long-term abnormalities are frequent and are associated with cranial irradiation
      in particular at young age, but less with tumour location, irradiation dose or
      surgery. CONCLUSIONS: Our preliminary data suggest that today intracerebral
      germinomas and mature teratomas have a good prognosis even when a relapse occurs.
      The outcome for mixed germ-cell tumours and malignant teratomas is less
      favourable. Although long-term sequelae are present in the majority of patients,
      there is some evidence that patients treated after 1990 suffer fewer severe long
      term defects, thereby indicating that recent treatment protocols may result in a
      reduction of sequelae.

PMID- 10907945
TI  - A phase II trial of palliative docetaxel plus 5-fluorouracil for squamous-cell
      cancer of the head and neck.
AB  - PURPOSE: A phase II study to determine the response rate and toxicity of
      docetaxel and 5-fluorouracil (5-FU) every four weeks ('TF'), in patients with
      incurable SCCHN. PATIENTS AND METHODS: Patients with metastatic or recurrent
      SCCHN with an ECOG PS < 3 were enrolled in an institutional review board approved
      trial. Prior induction or adjuvant chemotherapy was permitted provided six months
      had elapsed. The regimen was docetaxel 70 mg/m2 i.v., day 1 and 5-FU 800 mg/m2/d
      x 5 days, days 1-5, as a continuous intravenous infusion, repeated every 28 days.
      Planned intra-patient dose modifications were based on hematological, cutaneous,
      and gastrointestinal toxicities. Patients were removed from the study for
      progression of disease or unacceptable toxicity. RESULTS: Seventeen patients were
      enrolled. Fourty-six cycles of TF were administered. Reasons for discontinuance
      of TF included: progressive disease, 12 patients; toxicity, 3 patients;
      concomitant illness, 1 patient; death, 1 patient. The most common toxicities were
      neutropenia, mucositis, anemia, fatigue, alopecia, pain, diarrhea and nausea.
      Evaluation of responses to TF showed that there were four patients of seventeen
      (24%, 95% exact CI: 6.8-49.9) who achieved a PR or CR. Accrual was terminated
      after interim analysis of the response rate of the first 17 patients failed to
      exceed 4 of 17. CONCLUSIONS: The response rate to TF in patients with SCCHN was
      lower than expected. Trials of other regimens should take precedence over further
      exploration of the TF regimen.

PMID- 10907946
TI  - Phase II study of docetaxel in patients with liver metastases from breast cancer.
      UK study group.
AB  - BACKGROUND: Previous phase II studies of docetaxel have indicated that hepatic
      metastases from breast cancer respond well to first-line treatment with
      docetaxel. The objective of this prospective, open label phase II study therefore
      was specifically to evaluate the activity and safety of docetaxel in this
      indication. PATIENTS AND METHODS: The study recruited 47 women (mean age 50
      years, range 33-66 years) with hepatic metastases from breast cancer who
      fulfilled the eligibility criteria. After premedication with steroids, patients
      received a one-hour intravenous infusion of docetaxel 100 mg/m2 at three-weekly
      intervals for up to eight cycles. Response to treatment during medication was
      assessed after three, six and where appropriate, eight cycles and every three
      month follow-up thereafter, until disease progression or death. RESULTS: The best
      overall response rate (ORR) for evaluable patients was 64.3% (95% CI: 48.0
      78.5%). In terms of the primary efficacy parameters, the ORR at the sixth cycle
      of treatment was 62% (95% CI: 45%-80%) with 17% complete responses. The median
      duration of response was 139 days (95% CI: 111-216 days) and the median survival
      duration calculated on an intent-to-treat basis was 335 days (227-568 days, 95%
      CI). One (2%) toxic death was reported. CONCLUSIONS: Docetaxel is a highly
      effective cytotoxic agent in the treatment of patients with liver metastases from
      breast cancer.

PMID- 10907947
TI  - The addition of low-dose leucovorin to the combination of 5-fluorouracil-
      levamisole does not improve survival in the adjuvant treatment of Dukes' C colon
      cancer. IKN Colon Trial Group.
AB  - PURPOSE: To assess the effect of the addition of leucovorin to the combination of
      5-fluorouracil (5-FU)-levamisole on recurrence risk and overall survival in
      patients after a resection with curative intent of a Dukes' C colon cancer.
      PATIENTS AND METHODS: Five hundred patients with Dukes' C colon cancer were
      randomly assigned to adjuvant treatment for one year with 5-fluorouracil (450
      mg/m2 i.v. weekly) and levamisole (150 mg p.o. every two weeks), the C-group or
      with leucovorin (20 mg/m2 i.v.), 5-fluorouracil and levamisole, the L-group. The
      median follow-up for patients still alive is 36 months. Four patients were
      ineligible because of advanced disease at the time of randomisation. RESULTS:
      Sixty percent of the patients have completed all courses of chemotherapy. Of the
      remaining 40% of the patients who did not complete one-year treatment with
      chemotherapy, 46% discontinued because of toxic and/or emotional reasons. They
      were equally divided over both treatment arms. The addition of leucovorin
      increased toxicity (especially mucositis and conjunctivitis) without a
      significant increase in treatment withdrawal. Five-year disease-free interval (C
      group: 49%, L-group: 46%; log-rank test, P = 0.86) and overall survival (C-group:
      55%, L-group: 59%, log-rank test: P = 0.96) were very similar in both treatment
      arms. CONCLUSIONS: The addition of low dose leucovorin to the combination of 5
      fluorouracil and levamisole in a 12-month adjuvant therapy for curatively
      resected Dukes' C colon cancer patients does not improve disease-free interval
      nor overall survival. The addition of leucovorin to the combination of 5-FU
      levamisole increases toxicity. Therefore leucovorin 5-FU levamisole is not
      recommended in a 12 months adjuvant regime of Dukes' C colon cancer.

PMID- 10907948
TI  - First-line high-dose chemotherapy +/- radiation therapy in patients with
      metastatic germ-cell cancer and brain metastases.
AB  - PURPOSE: To examine the feasibility and efficacy of first-line high-dose
      chemotherapy (HD-CTX) in patients with advanced metastatic germ-cell tumors (GCT)
      and brain metastases. PATIENTS AND METHODS: Twenty-two patients with brain
      metastases at initial diagnosis were identified within a cohort of two hundred
      thirty-one consecutive patients with advanced metastatic disease, entered on a
      German multicenter trial between January 1993 and July 1998. All patients
      received first-line HD-CTX with cisplatin-etoposide-ifosfamide (HD-VIP) followed
      by autologous stem-cell transplantation. Brain irradiation (BRT) with 30-50 Gy +/
      10 Gy boost was applied in patients with symptomatic CNS disease or as
      consolidation in case of residual CNS lesions after HD-CTX. RESULTS: A median
      number of 4 HD-CTX cycles (range 2-5) were applied to the 22 patients. Ten
      patients received HD-CTX alone and twelve patients were treated with HD-CTX plus
      BRT. Median duration of WHO grade 4 granulocytopenia and thrombocytopenia was
      seven and five days after each cycle, respectively. Non-hematologic toxicity
      consisted mainly of mucositis/enteritis (WHO grade 3-4 32%). Two early deaths
      occurred in twenty-two patients (one CNS-bleeding/one sepsis). Fourteen of twenty
      patients achieved a CR/PRm- status. Twenty patients (91%) responded in the brain
      (55% CR/36% PR). Two-year progression-free and overall survival rates were 72%
      and 81%, respectively. These survival rates are substantially higher compared to
      the available data in the literature. CONCLUSIONS: High-dose chemotherapy with
      autologous stem-cell support +/- BRT appears to be feasible without increased
      therapy-related mortality in patients with advanced metastatic GCT and brain
      metastases. The results achieved emphasize the high chemosensitivity of CNS
      metastases from GCT and suggest a potential role for dose intensification. The
      dose of BRT in addition to HD-CTX may be tailored to the presence of clinical
      symptoms and the response of CNS metastases to chemotherapy.

PMID- 10907949
TI  - A study to investigate the prevalence, severity and correlates of fatigue among
      patients with cancer in comparison with a control group of volunteers without
      cancer.
AB  - BACKGROUND: Determining the prevalence of fatigue among cancer patients is
      complicated by the high prevalence of fatigue symptoms in the general population.
      The aim of this study was to determine the prevalence, severity and correlates of
      fatigue among both cancer patients and control subjects without cancer. PATIENTS
      AND METHODS: A total of 227 cancer patients and 98 control subjects were
      recruited to the study. They completed a number of questionnaires about fatigue,
      quality of life and psychological symptoms. The majority of subjects also
      underwent assessment of voluntary muscle function and nutritional status. Severe
      fatigue in the patients was defined as a score on the Fatigue Severity Scale in
      excess of the 95th percentile of the control group. RESULTS: The prevalence of
      severe fatigue was 15% among patients with recently diagnosed breast cancer, 16%
      among patients with recently diagnosed prostate cancer, 50% among patients with
      inoperable non small cell lung cancer and 78% among patients receiving specialist
      inpatient palliative care. In the patients a combination of dyspnoea,
      psychological distress, pain, and a measure of overall disease burden accounted
      for 56% of the variance in fatigue scores. CONCLUSIONS: Severe fatigue is a
      common problem among cancer patients, particularly those with advanced disease.
      Fatigue is significantly associated with the severity of psychological symptoms
      (anxiety and depression) and with the severity of pain and dyspnoea.

PMID- 10907950
TI  - Intra-arterial chemotherapy for unresectable pancreatic cancer.
AB  - BACKGROUND: A phase II trial of a new intra-arterial chemotherapy regimen for
      unresectable pancreatic cancer (UPC). PATIENTS AND METHODS: Ninety-six patients
      with UPC were treated with intra-arterial chemotherapy at three-weekly intervals.
      The schedule used was FLEC: 5-fluorouracil 1000 mg/m2, folinic acid 100 mg/m2,
      carboplatin 300 mg/m2; epirubicin 60 mg/m2. RESULTS: The overall response rates
      by CT-scan evaluation were: 15% partial response (PR), 44% stable disease (SD),
      17% progressive disease (PD). The overall median survival was 9.9 months, and
      10.6 and 6.8 for UICC stage III and IV, respectively. Pain reduction occurred in
      42% of patients. A weight gain > 7% from baseline occurred in 8% of patients. A
      total of 341 courses of FLEC were administered. Grade 3-4 hematological toxicity
      was seen in 25% of patients; ematemesis in 4%; grade 3 gastrointestinal toxicity
      in 3%; and grade 3 alopecia in 16%. One sudden death, a pre-infarction angina,
      and a transitory ischemic attack were observed. The only complication related to
      the angiographic procedure was an intimal dissection of the iliac artery.
      CONCLUSIONS: The intra-arterial FLEC regimen was well tolerated and active. It
      requires only one day of hospitalization. Efficacy could only be assessed in a
      randomized study against a gemcitabine containing regimen.

PMID- 10907951
TI  - Cisplatin, raltitrexed, levofolinic acid and 5-fluorouracil in locally advanced
      or metastatic squamous cell carcinoma of the head and neck: a phase I-II trial of
      the Southern Italy Cooperative Oncology Group (SICOG).
AB  - BACKGROUND: The combination of cisplatin (CDDP) and 5-fluorouracil (5-FU) can be
      regarded as a reference regimen in squamous cell carcinoma of the head and neck
      (SCCHN). Raltitrexed (Tomudex) is a direct and specific thymidilate synthase (TS)
      inhibitor, which has shown clinical activity against SCCHN in a previous phase I
      study, when combined with 5-FU and levo-folinic acid (LFA). Preclinical data
      support the combination of CDDP and raltitrexed. The aim of the present study was
      to evaluate the combination of cisplatin, raltitrexed. LFA and 5-FU in a phase I
      II study. PATIENTS AND METHODS: Patients with locally advanced or metastatic
      SCCHN were treated with a combination of cisplatin at the starting dose of 40
      mg/m2. followed by raltitrexed at the starting dose of 2.5 mg/m2 on day 1; levo
      folinic acid at fixed dose of 250 mg/m2, followed by 5-fluorouracil at the
      starting dose of 750 mg/m2 on day 2. Doses of the three cytotoxic agents were
      alternately escalated up to dose-limiting toxicity (DLT). Treatment was recycled
      every two weeks and given up to a maximum of eight courses; after chemotherapy,
      patients with locally advanced disease received a locoregional treatment.
      RESULTS: Forty-five patients were entered into the study. Six dose levels were
      tested. At CDDP 50 mg/m2, raltitrexed 3 mg/m2, 5-FU 900 mg/m2, four out of six
      patients showed DLT, which was in all cases grade 4 neutropenia. Therefore, this
      dose level was defined as maximum tolerated dose (MTD). CDDP 60 mg/m2,
      raltitrexed 2.5 mg/m2, LFA 250 mg/m2, 5-FU 900 mg/m2 was the dose level
      recommended for phase II. CDDP, Raltitrexed and 5-FU mean actually delivered dose
      intensities at the selected dose level were 26, 1.05, and 378 mg/m2/week,
      respectively. Neutropenia was the main side effect and was observed even at the
      lowest dose levels. Nonhematologic side effects were mild. Nine complete
      responses (20%) and twenty-one partial responses (47%) were observed, for an
      overall response rate of 67% (95% confidence interval (95% CI): 51%-80%),
      according to intention to treat analysis. Fifteen of fifteen patients (100%)
      treated at the dose level selected for phase II had an objective response (5
      complete responses, 10 partial responses). CONCLUSIONS: The results of our dose
      escalation clearly demonstrate that it is possible to combine CDDP, raltitrexed,
      and modulated 5-FU at effective doses, without unexpected toxicities. The
      response data point to an impressive clinical activity, which will be better
      defined by an ongoing large phase II study.

PMID- 10907952
TI  - Comparative study of clinical, pathological and biological characteristics of
      symptomatic versus asymptomatic breast cancers.
AB  - BACKGROUND: It is well known that mammographic screening reduces breast cancer
      mortality. One possible explanation for this effect is that screening makes it
      possible to detect smaller breast cancers with fewer involved nodes, but another
      hypothesis is that some screening-detected tumors are in a pathologically and
      biologically different phase of evolution from those that are detected
      clinically. The aim of the present study was to compare the biological,
      pathological and clinical characteristics of symptomatic vs. asymptomatic breast
      cancers. PATIENTS AND METHODS: The study considers a series of 1916 consecutive
      patients who underwent surgery for stage I and II infiltrating breast cancer at
      Verona hospitals after having undergone ultrasound and mammography (at least one
      of which was positive). They were divided into two groups on the basis of why
      they decided to undergo the imaging examinations: group A refers to the 1247
      patients with a palpable lump, and group B to the 616 who were asymptomatic.
      RESULTS: The patients in group A were older, and had larger tumors and a higher
      percentage of positive nodes than those in group B; they also had significantly
      higher grade tumors, higher Ki-67 levels, and a higher percentage of ER and PgR
      negative and c-erbB-2 positive tumors (all of the P-values were significant). A
      logistic regression analysis adjusted for tumor diameter and age showed a
      reduction in the significance of each of the considered variables, but all of
      them remained significantly associated with the modality of diagnosis except ER,
      PgR and c-erbB-2. CONCLUSIONS: Our results suggest that asymptomatic tumors are
      biologically different from their clinically presenting counterparts, thus
      confirming the hypothesis that progression towards greater malignancy may occur
      during the natural history of breast cancer.

PMID- 10907953
TI  - Combined 4-hydroxy-ifosfamide and vinorelbine treatment in established and
      primary human breast cell cultures.
AB  - BACKGROUND: Vinorelbine and ifosfamide are active drugs against breast cancer,
      but the best treatment schedule has yet to be defined by preclinical or clinical
      studies. The antitumor activity of 4-hydroxy-ifosfamide (4-OH-IF), the active
      form of ifosfamide, and vinorelbine (VNB) and their interaction were investigated
      in two established breast cancer cell lines (MCF-7 and BRC-230) and in 10 primary
      breast cancer cultures. MATERIALS AND METHODS: Cytotoxic activity was evaluated
      by a highly efficient clonogenic assay (HECA). The median-effect principle was
      applied to evaluate synergistic and antagonistic interactions and the
      corresponding combination index values were calculated. Cell cycle perturbations
      were analysed by flow cytometry. RESULTS: In MCF-7 and BRC-230 cell lines the
      sequence VNB for 4 hours followed by 4-OH-IF for 24 hours produced an
      antagonistic effect. Conversely, the inverse sequential scheme, 4-OH-IF-->VNB
      provided synergistic effects on both cell lines. The synergism was associated
      with a strong block in the G2-M phase. Synergistic activity of 4-OH-IF-->VNB
      sequence was confirmed in 7 of 10 primary breast cancer cultures. CONCLUSIONS: In
      conclusion, the sequence 4-OH-IF-->VNB appeared to be the most effective scheme
      both in established cell lines and in primary breast cancer cultures.

PMID- 10907954
TI  - Gemcitabine for relapsed or resistant lymphoma.
AB  - BACKGROUND: Gemcitabine therapy has not been widely assessed in the treatment of
      hematological malignancies. We have examined the efficacy and safety of
      gemcitabine in patients with relapsed or resistant lymphoma. PATIENTS AND
      METHODS: Gemcitabine (1 g/m2) was given weekly for 7 consecutive weeks, followed
      by a week off treatment. The drug was then given for 3 consecutive weeks,
      followed by a week off treatment; this regimen was continued until disease
      progression or drug intolerance. Fifteen patients have enrolled. Most have been
      extensively pre-treated for advanced diffuse large-cell or mantle-cell lymphoma.
      RESULTS: The drug was well tolerated; no patient suffered treatment-related
      sepsis, hemorrhage or death. Non-hematopoietic toxicity led to discontinuation of
      gemcitabine therapy in two patients. Dose reductions or delays were required for
      about two-thirds of treatments. Of 13 evaluable patients, one had a complete
      response, 3 a partial response, 3 stable disease, and 6 disease progression.
      After 6 infusions of gemcitabine, a patient with advanced Hodgkin's disease has
      had a complete remission lasting 21 months. CONCLUSIONS: Gemcitabine has
      substantial activity and acceptable toxicity in heavily pre-treated patients with
      advanced lymphoma. Further study is warranted.

PMID- 10907955
TI  - Oncology healthcare professionals' attitudes toward elderly people.
AB  - BACKGROUND: Healthcare professionals are known to be particularly susceptible to
      ageist stereotyping because of increased exposure to elderly and infirm
      individuals. Demographic changes resulting in increasing numbers of elderly
      people and increased cancer incidence with age make it imperative to understand
      oncology healthcare professionals' attitudes towards older people. DESIGN: A
      descriptive survey design was conducted, within a regional Cancer Centre, to
      evaluate oncology healthcare professionals' attitudes towards elderly people. The
      measurement scale used was Kogan's Old People Scale. RESULTS: Regardless of
      gender, profession and clinical experience persistently negative attitudes were
      displayed towards elderly people. No statistically significant difference was
      detected between gender, profession, clinical experience or specialist education
      and although small in number, no large differences in scores were notable between
      group means. CONCLUSIONS: If oncology healthcare professionals are to provide
      optimal treatment and care for elderly people, negative attitudes must be
      addressed. These results indicate the need for a radical cultural shift in
      attitudes, especially when considered in conjunction with changing demographics
      and increased cancer incidence with age.

PMID- 10907956
TI  - Cost-analysis of high-dose chemotherapy and peripheral blood stem-cell support in
      patients with solid tumors.
AB  - BACKGROUND: The use of High-dose chemotherapy (HDC) with peripheral blood stem
      cells (PBSC) rescue in the treatment of solid tumors is controversial, and may be
      an important determinant of HDC and PBSC use in the future. Until the use of
      these procedures is proven through disease-free survival and overall survival
      compared with standard-dose chemotherapy, the associated cost is also under
      discussion. PATIENTS AND METHODS: We evaluate 27 consecutive patients with solid
      tumors who underwent HDC and PBSC rescue, through an accurate review of medical
      records and cost estimate for each patient. RESULTS: Median age was 45 years.
      Fifteen had breast cancer, six non-Hodgkin's lymphoma and six other solid tumors.
      The mean hospital length of stay was 21 days and mean cost was 21,445 US dollars
      (21,232 euro). Mean cost was clearly lower for the 9 patients treated within
      phase III trials, 17,571 US dollars (17,747 euro) than for the remaining 18
      patients, treated in phase I-II trials, 22,747 US dollars (22,975 euro) (P <
      0.001). The distribution of costs shows that wages and pharmacy account for 72%
      of total cost. The distribution of pharmacy costs per patient shows that
      chemotherapy (56% of pharmacy costs) and antibiotics (26%) account for most of
      the cost of medication. CONCLUSIONS: Our cost estimates agree with those of most
      countries with national health insurance programs, and are lower than those from
      the USA. As wages and pharmacy account for more than 70% of the costs, the great
      different among the costs estimates compared are due essentialy to doctors fees
      or salary and drugs utilization. Anyway, taking HDC with PBSC rescue as a model
      for a therapy that is more aggressive than standard, and that is associated to a
      possible survival improvement in indications such as relapsed high-grade non
      Hodgkin's lymphoma, an adequate cost analysis is crucial both to measure cost
      effectiveness and to establish payment to health care providers.

PMID- 10907957
TI  - Ifosfamide plus oral etoposide salvage chemotherapy for platinum-resistant
      paclitaxel-pretreated ovarian cancer.
AB  - BACKGROUND: The prognosis of platinum resistant ovarian cancer is very poor and
      the treatment of choice has not been clearly defined. PATIENTS AND METHODS: We
      conducted a phase II study with the combination of ifosfamide i.v. at 2.25 g/m2
      (days 1, 2) and etoposide per os at 100 mg daily (days 1-10) every four weeks. To
      be eligible for the study patients had to be resistant to platinum and paclitaxel
      pretreated. RESULTS: Forty-one patients entered the study. The median interval
      from the previous chemotherapy was 3.9 months. The median number of previous
      chemotherapeutic regimens was 2. Severe toxicities included neutropenia (41% of
      patients), leukopenia (29%) and thrombocytopenia (13%). Thirty-five patients are
      assessable for response. Nine patients responded (22% of the eligible, 26% of the
      assessable), four of them demonstrated complete response to chemotherapy (10% and
      12%, respectively), while three patients demonstrated stabilization of their
      progressive disease. After a median follow-up of 18 months, time to progression
      is 3 months (range 0.9-14.4), duration of response is 9 months (2.5-11) and
      median survival is 13 months (2.5-37.4+). CONCLUSIONS: The combination of
      ifosfamide with oral etoposide appears to have significant but manageable
      toxicity and encouraging efficacy in platinum resistant ovarian cancer.

PMID- 10907958
TI  - A phase I study of gemcitabine and epirubicin for the treatment of platinum
      resistant or refractory advanced ovarian cancer.
AB  - BACKGROUND: Gemcitabine is active in patients with otherwise resistant or
      refractory ovarian cancer. As the drug is well tolerated, studies using
      gemcitabine combined with other antineoplastic agents are needed. The aim of the
      study was to determine the maximum tolerated dose (MTD) of epirubicin combined
      with gemcitabine, with and without support of G-CSF. PATIENTS AND METHODS:
      Patients with platinum-resistant or refractory ovarian cancer were eligible.
      Gemcitabine (G) (starting dose 800 mg/m2 day 1 and 8; 200 mg/m2 escalation per
      level) and epirubicin (E) (starting dose 60 mg/m2 day 1; 15 mg/m2 escalation per
      level) were given every 21 days for four to six cycles. G-CSF (filgrastim 5
      microg/kg/die) was given in case of grade 4 neutropenia (levels without support)
      or from day 9 up to leukocyte count > 10.000/mm3 after nadir (levels with
      support). Cohorts of three patients were enrolled at each level, and another
      three patients were planned, if one dose-limiting toxicity (DLT) was registered.
      MTD was determined first without and then with G-CSF. RESULTS: Four levels were
      studied (G 800 + E 60; G 1000 + E 60; G 1000 + E 75; G 1000 + E 75 + G-CSF) with
      four, four, three and three patients enrolled, respectively. DLT (grade 4 febrile
      neutropenia) was observed in two patients at level 3. Thus, G1000 + E 60 mg/m2
      was the MTD without G-CSF. The addition of prophylactic G-CSF did not allow a
      further increase of the dose and grade 4 thrombocytopenia was the DLT at level 4.
      Non-hematological toxicity was mild. Grade 2 mucositis was reported in four
      patients. Among the 13 patients with measurable or evaluable disease, 3 partial
      responses were observed for an overall response rate of 23.1%. CONCLUSIONS: The
      combination of gemcitabine 1000 mg/m2 (day 1, 8) and epirubicin at 60 mg/m2 (day
      1) is a feasible therapy. Grade 4 neutropenia is frequent and G-CSF support is
      often required. With prophylactic support of G-CSF, the DLT is thrombocytopenia.

PMID- 10907959
TI  - Is the international prognostic score for advanced stage Hodgkin's disease
      applicable to early stage patients? German Hodgkin Lymphoma Study Group.
AB  - BACKGROUND: The seven-factor International Prognostic Score (IPS) has been
      developed and verified for patients with advanced stage Hodgkin's disease (HD).
      This report aims to assess the predictive power of the IPS for early stage HD
      patients. PATIENTS AND METHODS: Data on patient characteristics, therapy and
      follow-up were available for 1424 adult patients in clinical stages I-IIIA
      treated for primary HD in two German Hodgkin's Lymphoma Study Group (GHSG) trials
      (1988-1994). Patients with risk factors or in stage IIIA received chemo
      radiotherapy (CMT; trial HD5); others received extended field radiotherapy (RT)
      alone (HD4). The IPS could be calculated for 712 HD5 and 249 HD4 patients (70%).
      The prognostic value of the IPS and its component factors was assessed using Cox
      proportional hazards regression. A search was made for additional factors which
      could add predictive power to the IPS. RESULTS: The IPS identified 40% of the
      unfavourable early stage patients with an 8% lower disease-free survival at six
      years (hazard ratio 1.66, P = 0.0018). The factor 'low albumin' was the only
      score component giving a significant individual contribution. Allowing for the
      IPS, extranodal involvement, particularly in stages IIB-IIIA, was associated with
      worse prognosis, but no further significantly prognostic factors were revealed.
      The IPS identified a similar hazard ratio in HD4, although here the effect was
      not significant. CONCLUSIONS: The IPS for advanced HD has modest predictive
      ability in unfavourable early stage patients. Modification of the IPS for use
      with early stages may improve its prognostic power.

PMID- 10907960
TI  - Expression of sodium iodide symporter in metastatic and follicular human thyroid
      tissues.
AB  - Active iodide uptake across the basal membrane mediated by human sodium iodide
      symporter (hNIS) has been shown to be a process coupled with the flow of sodium.
      There is still controversy as to the amount of hNIS expression present in
      different kinds of human thyroid cancer tissues. In this study, we present a 58
      year-old women with follicular thyroid carcinoma with vertebra and skull
      metastases. 201Tl and 5 mCi 131I scans clearly demonstrated the metastatic
      lesions in the brain of this patient. Thyroid and metastatic tissues were then
      obtained for this study, which is aimed at comparing the iodide trapping ability
      in vivo and in vitro of hNIS, and then comparing their expression in both thyroid
      tissue and metastatic tissues. Polyclonal antibodies to hNIS and competitive RT
      PCR were used to analyze the symporter protein and mRNA expressed in follicular
      human thyroid and metastatic tissues. Positive staining of the symporter protein
      was performed in the follicular thyroid carcinomas, otherwise, the metastatic
      tissues could not have demonstrated the protein in the staining. Follicular
      thyroid carcinoma tissues from thyroid were revealed around 5 pg hNIS expressed
      in follicular thyroid carcinoma tissues from the thyroid. Otherwise, there was
      almost an absence of hNIS expression in the metastatic tissue. These
      discrepancies of the expression in hNIS in vivo and in vitro studies need further
      investigation.

PMID- 10907961
TI  - Adjuvant chemotherapy in node negative breast cancer: patterns of use and
      oncologists' preferences.
AB  - BACKGROUND: A worldwide variation in policy is seen regarding adjuvant systemic
      treatment for node negative breast cancer (NNBC). After the first presentations
      of the 10-year EBCTCG results, a study was carried out in the Netherlands to
      assess patterns of care and to obtain the views of oncologists as to what
      constitutes a worthwhile benefit from treatment. METHODS: A questionnaire
      regarding patterns of use of and preferences for adjuvant chemotherapy in younger
      women was mailed to surgical, medical and radiation oncologists in the
      Netherlands. RESULTS: Thirty-five percent stated that NNBC patients under 50 in
      their hospital never received adjuvant chemotherapy. The majority considered a 10
      year survival gain of 6%-10% sufficient to warrant the use of chemotherapy in
      patients under 50. Surgical oncologists required a larger benefit from treatment
      than radiotherapists and medical oncologists. The more frequently oncologists
      treated patients in a research context, the less benefit they required from
      treatment to make it worthwhile. CONCLUSIONS: Data such as these are valuable
      input into the process of guideline development, and may help discussion within
      the profession as to what benefit offsets the burden of treatment.

PMID- 10907962
TI  - Circulating melanoma-associated markers detected by RT-PCR in patients with
      classic Kaposi's sarcoma.

PMID- 10907964
TI  - Nalmefene to prevent epidural narcotic side effects in pediatric patients: a
      pharmacokinetic and safety study.
AB  - STUDY OBJECTIVE: To determine the pharmacokinetics and preliminary efficacy of
      nalmefene in children in preventing epidural-induced narcotic side effects.
      DESIGN: Double-blind, placebo-controlled study. SETTING: University-affiliated
      children's hospital. PATIENTS: Thirty-four children (aged 2-12 yrs) undergoing
      cardiothoracic surgery with epidural anesthesia. INTERVENTIONS: Patients were
      randomized to receive intravenous bolus nalmefene 1 microg/kg or placebo.
      MEASUREMENTS AND MAIN RESULTS: Six blood samples (one before nalmefene
      administration and five from 13 randomly designated time points) from each
      patient were assayed to determine plasma nalmefene concentrations. Patients were
      assessed for pain, nausea, vomiting, and urinary retention for 24 hours after
      administration. Concentration-time data were analyzed by a limited sampling
      strategy with adult pharmacokinetic parameters used as Bayesian priors. A two
      compartment, first-order model was fitted to the data using ADAPT II.
      Pharmacokinetic parameter estimates in these patients were similar to values
      reported in adults. The initial disposition half-life (t(1/2alpha)) was 0.36+/
      0.11 hour, the terminal elimination half-life (t(1/2beta)) 8.7+/-2.3 hours,
      clearance 0.729+/-0.172 L/kg/hr, and steady-state volume of distribution 7.21+/
      2.49 L/kg. Ability to prevent epidural narcotic-induced side effects could not be
      documented at the 1-microg/kg dose. No statistically significant differences were
      noted between study and placebo groups with regard to pain, nausea, vomiting, or
      urinary retention. CONCLUSION: Nalmefene has similar pharmacokinetics in children
      as in adults. It was administered safely to these patients and did not produce
      unmanageable pain.

PMID- 10907963
TI  - The risk of gastrointestinal bleed, myocardial infarction, and newly diagnosed
      hypertension in users of meloxicam, diclofenac, naproxen, and piroxicam.
AB  - STUDY OBJECTIVE: To obtain formally quantified data on the relation of meloxicam
      to newly diagnosed gastrointestinal problems, myocardial infarction, or treated
      hypertension. DESIGN: Nested case-control study. SETTING: United Kingdom-based
      General Practice Research Database. PATIENTS: Patients who received prescriptions
      for meloxicam, diclofenac, naproxen, or piroxicam formed the study population.
      Cases were people who developed gastrointestinal problems, myocardial infarction,
      or hypertension. MEASUREMENTS AND MAIN RESULTS: Relative risk estimates for
      developing the study outcomes were provided for each study nonsteroidal
      antiinflammatory drug (NSAID), with diclofenac as the reference drug. In no
      instance was meloxicam associated with an increased risk for a study outcome.
      CONCLUSION: Compared with the other NSAIDs, meloxicam was not materially
      associated with any study outcomes. This study provides reassurance to those
      prescribing this newer class of NSAIDs.

PMID- 10907966
TI  - Comparison of anticoagulant effects and safety of argatroban and heparin in
      healthy subjects.
AB  - STUDY OBJECTIVE: To evaluate and compare the relationship between dosage and
      coagulation parameters, as well as safety profiles, of ascending bolus and
      infusion dosages of argatroban versus heparin in three phase I studies. DESIGN:
      Two randomized, double-blind studies compared argatroban and heparin, and one
      open-label, dose-escalation study further evaluated argatroban. SETTING:
      University teaching hospital clinical research unit. PATIENTS: Healthy men (aged
      22-62 yrs). INTERVENTION: In the first study, 36 subjects received an argatroban
      30-, 60-, 120-, or 240-microg/kg bolus, or a heparin 30-, 60-, 120-, or 240-U/kg
      bolus for three subjects, then amended to 15, 30, 60, or 120 U/kg. In the second
      study, 37 subjects received argatroban 1.25, 2.5, 5, or 10 microg/kg/minute with
      or without a 250-microg/kg bolus, or heparin 0.15, 0.20, 0.25, or 0.30
      U/kg/minute with or without a 125-U/kg bolus. In the third study (open-label),
      nine subjects received an argatroban 250-microg/kg bolus plus an infusion of 15,
      20, 30, and 40 microg/kg/minute. MEASUREMENTS AND MAIN RESULTS: When administered
      as a bolus dose in the first study, argatroban and heparin both produced dose
      related increases in activated clotting time (ACT) and activated partial
      thromboplastin time (aPTT) within 10 minutes of administration. Dissipation of
      anticoagulant effect was approximately 4-fold faster for argatroban than for
      heparin. When administered by infusion with or without a bolus in the second
      study, argatroban, but not heparin, produced predictable dose-related increases
      in ACT and aPTT that were generally consistent across both effect measures and
      modes of administration. Effect steady state was attained by five or more
      subjects per dosing group receiving argatroban (5-9) but typically two or fewer
      subjects per group receiving heparin (0-7). Furthermore, upon cessation of
      infusion, anticoagulant effects dissipated faster for argatroban (effect half
      life 18-41 min) than for heparin (effect half-life 23-134 min). When argatroban
      was infused without a bolus, peak and effect steady-state values for ACT and aPTT
      generally were attained within 1-3 hours. Data from the second and third studies
      show that for argatroban dosages up to 40 microg/kg/minute, plasma drug
      concentrations attained at 4 hours of infusion increased linearly with dose, and
      weight-adjusted plasma clearance was dose independent. In all studies, argatroban
      and heparin were well tolerated. CONCLUSION: Anticoagulation was more predictable
      with argatroban than with heparin as measured by ACT and aPTT, with comparable
      safety profiles.

PMID- 10907965
TI  - Lack of interaction between citalopram and the CYP3A4 substrate triazolam.
AB  - STUDY OBJECTIVES: To determine the effect of the selective serotonin reuptake
      inhibitor citalopram on plasma levels of triazolam, and to determine the effect
      of a single dose of triazolam on steady-state levels of citalopram and its major
      metabolites. DESIGN: Open-label, multidose study. SETTING: Clinical Studies,
      Ltd., Fort Lauderdale, Florida. PARTICIPANTS: Eighteen healthy male and female
      volunteers. INTERVENTIONS: Subjects received triazolam 0.25 mg alone and another
      0.25-mg dose after 4 weeks of citalopram 20 mg/day for 1 week, followed by 3
      weeks of citalopram 40 mg/day MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic
      parameters were determined after single-dose administration of triazolam alone,
      after administration of citalopram alone at steady state, and after
      coadministration of the drugs. The pharmacokinetics of triazolam and its
      metabolite alpha-hydroxytriazolam were unchanged by citalopram coadministration.
      Triazolam appeared to be absorbed slightly more quickly during coadministration.
      Citalopram kinetics were unaffected by coadministration. CONCLUSION: No
      pharmacokinetic interaction between the drugs was observed, suggesting that
      triazolam and other cytochrome P450 3A4 substrates can be coadministered safely
      with citalopram.

PMID- 10907967
TI  - Enoxaparin and bleeding complications: a review in patients with and without
      renal insufficiency.
AB  - STUDY OBJECTIVE: To compare the frequency of bleeding complications from
      enoxaparin in patients with normal renal function versus patients with renal
      insufficiency. DESIGN: Retrospective chart review. SETTING: University-based
      tertiary care center. PATIENTS: One hundred six patients who received two or more
      doses of enoxaparin. MEASUREMENTS AND MAIN RESULTS: Total bleeding complications
      occurred in 22% of patients with normal renal function and 51% with renal
      insufficiency (p<0.01). Major bleeds were also significantly different, 2% and
      30%, respectively (p<0.001). No patients with normal renal function were given
      fresh-frozen plasma or packed red blood cells, whereas in those with renal
      insufficiency, 13% and 32%, respectively, received these products (p<0.01).
      CONCLUSION: Enoxaparin may have resulted in increased bleeding complications and
      use of blood products in patients with renal insufficiency. Prospective studies
      need to be conducted to define the drug's role and dosage adjustments in these
      patients.

PMID- 10907968
TI  - Dofetilide, a new class III antiarrhythmic agent.
AB  - Dofetilide is a new antiarrhythmic agent recently approved for conversion and
      maintenance of sinus rhythm in patients with atrial fibrillation (AF) and atrial
      flutter (AFl). It is a class III antiarrhythmic that works by selectively
      blocking the rapid component of the delayed rectifier outward potassium current.
      Dofetilide prolongs the effective refractory period in accessory pathways, both
      anterograde and retrograde. This can be seen on the electrocardiogram through a
      dose-dependent prolongation of the QT and QTc intervals, with parallel increases
      in ventricular refractoriness. Approximately 80% of drug is excreted in urine, so
      dosing must be based on creatinine clearance. The elimination half-life is
      approximately 10 hours. In clinical trials dofetilide was superior to flecainide
      in converting patients with AFl to normal sinus rhythm (NSR; 70% vs 9%, p<0.01).
      It also was more effective than sotalol in converting patients with both AF and
      AFl to NSR (29% vs 6%, p<0.05) and maintaining them in NSR for up to 1 year. Most
      patients converted within 24-36 hours. Dofetilide has a favorable risk:benefit
      profile. Torsades de pointes is the most serious side effect; it occurs in 0.3
      10.5% of patients and is dose related. To minimize the risk of induced
      arrhythmia, patients who start or restart the drug should be hospitalized a
      minimum of 3 days for creatinine clearance measurements, continuous
      electrocardiographic monitoring, and cardiac resuscitation, if necessary.

PMID- 10907969
TI  - Advances in the treatment of congestive heart failure: new approaches for an old
      disease.
AB  - Heart failure is a symptom complex of varied etiology associated with substantial
      mortality. Approximately 5 million Americans have the disease, with 400,000 new
      cases diagnosed each year. Despite better understanding of its pathophysiology,
      therapeutic options remain suboptimal and the syndrome remains associated with
      high rates of hospitalization and loss of economic productivity. Management
      traditionally included vasodilators, diuretics, and digoxin, with a focus on
      controlling symptoms and improving ejection fraction and exercise capacity. Drug
      therapy now is focused on improving survival, with a reduction in health care
      costs related to hospitalizations. Drugs with a proven benefit in reducing
      morbidity and mortality are angiotensin-converting enzyme inhibitors, beta
      blockers, and the combination of hydralazine plus a nitrate. Diuretics, digoxin,
      dihydropyridine calcium channel blockers, phosphodiesterase inhibitors,
      catecholamine infusions, amiodarone, left ventricular assist devices, and
      transplantation are also options.

PMID- 10907970
TI  - Periodontal disease and atherosclerotic cardiovascular disease: confounding
      effects or epiphenomenon?
AB  - Recent evidence suggests that periodontal disease may predispose to
      atherosclerotic cardiovascular disease. Data support mechanisms of host-derived
      local and systemic proinflammatory responses similar to atherosclerosis,
      consisting of monocytic-derived cytokines and other inflammatory mediators, which
      are induced by periodontal pathogens and its endotoxin, lipopolysaccharide. These
      mechanisms may contribute to the start of vascular endothelial dysfunction and
      further sequelae leading to atherosclerosis. Experimental evidence and biologic
      plausibility appear to support this proposal. However, clinical evidence from a
      MEDLINE search from January 1966-December 1999 proposed a weak or no correlation
      primarily due to confounding factors. The aim of care is to reduce vulnerable
      pathogens from the infected periodontium by standard treatment; however, new
      approaches appear promising. Increased awareness of a potential link among
      infective agents, immunoinflammatory processes, and atherosclerosis may clarify
      clinical implications.

PMID- 10907972
TI  - Using focus groups to identify barriers to drug use in patients with congestive
      heart failure.
AB  - STUDY OBJECTIVE: To explore barriers to adherence to drug therapy identified by
      patients with congestive heart failure (CHF). SETTING: University-associated
      heart failure clinic and a family practice clinic. PATIENTS: Twenty-six patients
      with CHF. INTERVENTION: Four focus group sessions. MEASUREMENTS AND MAIN RESULTS:
      Participants were asked to describe how their lives changed as a result of
      developing CHF and the challenges they face when taking drugs for the condition.
      In the second half of each session, participants were asked for their opinions
      regarding various teaching and memory aids for improving adherence with therapy.
      They recognized the value of these aids and often created their own when health
      care professionals did not supply them. Transcripts were reviewed and comments
      grouped to identify patient-perceived barriers to adherence. The disease placed
      significant limitations on lifestyle. Furosemide had dramatic effects on daily
      activities, and some patients altered the dosing schedule to accommodate their
      plans. Influences on adherence were generalized into five themes: confidence in
      health care providers; their own knowledge regarding the disease and drugs used
      to treat it; previous experience with drugs; support from family and friends; and
      ease of communication with health care professionals. CONCLUSION: Focus groups
      are an effective and efficient method to explore patients opinions of barriers to
      drug therapy adherence. Such information can have a direct impact on management
      of patients with CHF. Information gathered in this study will be used to
      construct a survey to measure barriers to drug adherence and design interventions
      to improve adherence.

PMID- 10907971
TI  - Pharmacoeconomic assessment of HMG-CoA reductase inhibitor therapy: an analysis
      based on the CURVES study.
AB  - We conducted a post hoc pharmacoeconomic analysis of a multicenter, open-label,
      randomized, parallel-group, 8-week efficacy-safety comparison of five HMG-CoA
      reductase inhibitors-atorvastatin, fluvastatin, lovastatin, pravastatin, and
      simvastatin. The 534 patients requiring cholesterol-lowering therapy took the
      drugs for 8 weeks with 15 different regimens. Low-density lipoprotein (LDL) was
      measured after 6 weeks of diet (baseline) and after 8 weeks of treatment with a
      study drug. At dosages of 10, 20, and 40 mg/day, atorvastatin was associated with
      significantly greater reductions in LDL than equivalent dosages of the other
      agents. Cost-effectiveness calculated as the annual acquisition cost/percentage
      LDL reduction was greatest with atorvastatin 10 mg ($17.96), fluvastatin 40 mg
      ($19.83), atorvastatin 20 mg ($22.85), and atorvastatin 40 mg ($24.96). All other
      dosages were above $25.00/year/percentage LDL reduction. Atorvastatin was the
      most cost-effective HMG-CoA reductase inhibitor. Fluvastatin 40 mg/day also had a
      favorable cost:effectiveness ratio but lowered LDL only by 23%.

PMID- 10907973
TI  - Quality of pharmacotherapy consultations provided by drug information centers in
      the United States.
AB  - We evaluated the performance of 116 U.S. drug information centers in responding
      to specific questions about drugs. The primary measures were correctness of
      responses and extent of probing for patient data. Questions addressed the effect
      of ranitidine on blood alcohol concentrations, the potential interaction between
      didanosine and dapsone, prevention of nonsteroidal antiinflammatory drug (NSAID)
      induced peptic ulcers, and use of erythromycin for diabetic gastroparesis. The
      percentages of centers providing correct overall responses were 70% for the
      ranitidine question, 90% for the didanosine-dapsone question, 8% for the NSAID
      question, and 20% for the erythromycin question. For the three patient-specific
      questions, the percentages of centers eliciting vital patient data were 27% for
      the didanosine-dapsone question, 86% for the NSAID question, and 5% for the
      erythromycin question. In providing pharmacotherapy consultations, drug
      information centers generally failed to obtain pertinent patient data, thereby
      risking incorrect responses and inappropriate recommendations.

PMID- 10907974
TI  - Development and validation of the satisfaction with pharmacist scale.
AB  - To assess patients' satisfaction with pharmacists, seven questions were developed
      with semistructured input from 5 pharmacy practice faculty members and 11
      patients with cancer. The study identified 1617 English- and Spanish-speaking
      patients with cancer or human immunodeficiency virus infection or acquired
      immunodeficiency syndrome who participated in a multisite validation of the
      Functional Assessment of Cancer Therapy Scale. Of these, 1124 had seen a
      pharmacist in the past 7 days and therefore were eligible; 608 spoke English and
      516 Spanish. The seven items on the Satisfaction with Pharmacist (SWiP) scale
      were rated on a five-point Likert scale (0 = not at all to 4 = very much). The
      reliability of the English and Spanish versions was evaluated by Cronbach's alpha
      coefficients. The unidimensionality and construct validity were analyzed with the
      Rasch rating scale model. The alpha coefficients for the English and Spanish
      versions were 0.90 and 0.92, respectively. Rasch analyses of item responses
      showed that none of the items in either language was a misfit, which supported
      their ability to measure a unidimensional construct. Item difficulty plots
      revealed that no item exhibited differential functioning, indicating that the
      items performed the same in both languages. The SWiP scale has reliable and valid
      psychometric properties in English and Spanish and can be used to document the
      value of the pharmacist-patient relationship. It is easy to administer and is
      ready for further use and evaluation to determine and document outcomes of
      pharmaceutical care.

PMID- 10907975
TI  - Diabetes mellitus associated with clozapine therapy.
AB  - Clozapine is an atypical antipsychotic that is associated with certain adverse
      effects that limit its usefulness. Published case reports have associated
      clozapine with impairment of glucose tolerance, including the onset or
      exacerbation of diabetes mellitus. We report two patients who experienced
      diabetes mellitus associated with the agent.

PMID- 10907976
TI  - Leukocytoclastic vasculitis: is propranolol implicated?
AB  - Drugs frequently cause cutaneous adverse reactions. The suspected agent is
      sometimes difficult to identify, especially in patients receiving multidrug
      treatment and with underlying illnesses that may contribute to the clinical
      picture. In our patient, propranolol-induced leukocytoclastic vasculitis was
      diagnosed by exclusion.

PMID- 10907977
TI  - Potential interaction between ritonavir and carbamazepine.
AB  - Ritonavir (RTV), a protease inhibitor, and carbamazepine (CBZ), an
      anticonvulsant, were administered concurrently to a patient who had human
      immunodeficiency virus infection and epilepsy. The combination resulted in
      elevated serum concentrations of CBZ, with accompanying vomiting, vertigo, and
      transient liver dysfunction. After discontinuing RTV and reducing the dosage of
      CBZ, the serum concentration of CBZ returned to the optimal range, symptoms
      subsided, and liver function returned to baseline. Carbamazepine is metabolized
      in the liver to a large extent by the cytochrome P450 (CYP) system, especially
      CYP3A4, 2C8, and 1A2, whereas RTV is metabolized primarily by CYP3A and is a
      potent inhibitor of this enzyme. Careful clinical monitoring may help prevent
      adverse drug interactions when these drugs are administered concurrently.

PMID- 10907978
TI  - Bone marrow granulomas possibly associated with amiodarone.
AB  - Amiodarone is a class III antiarrhythmic agent that is effective in treating
      different types of cardiac dysrhythmias. It was approved only for treatment of
      life-threatening ventricular dysrhythmias refractory to other therapy; however,
      its use for atrial dysrhythmias such as atrial fibrillation is well accepted.
      Adverse effects associated with amiodarone include pulmonary, hepatic, thyroid,
      ocular, and neurologic toxicities. Our patient experienced intermittent fever,
      night sweats, and fatigue while taking the drug for treatment of atrial
      fibrillation. Bone marrow biopsy showed granuloma formation after 17 months of
      therapy with amiodarone. Amiodarone was discontinued due to significant
      hypotension and shortness of breath. To our knowledge, this is the third case
      report of granuloma formation in bone marrow possibly associated with this agent.

PMID- 10907979
TI  - The FDA: protector or puppet?

PMID- 10907980
TI  - Toxic acetaminophen doses are toxic or do you know where your acetaminophen is
      today?

PMID- 10907982
TI  - Epistaxis associated with elevation of INR in a patient switched to generic
      warfarin--another view.

PMID- 10907981
TI  - Epistaxis associated with elevation of INR in a patient switched to generic
      warfarin--a comment.

PMID- 10907984
TI  - Hidden problems with herbal remedies.

PMID- 10907983
TI  - More about orlistat.

PMID- 10907985
TI  - White paper on herbal products. American College of Clinical Pharmacy.
AB  - Individuals increasingly are taking a more active role in their health care, and
      herbal products have emerged as a common choice among self-care therapies.
      Pharmacists are active participants in the care of patients who are taking herbal
      products. Currently, most pharmacists are not educated adequately about herbal
      products and other types of alternative medicine. Furthermore, good information
      about many of these products is not available. These combined factors present a
      challenge for pharmacists as they seek to provide optimal care and counseling to
      patients who use herbs or supplements. We recommend the following actions to
      place pharmacists in better positions as effective agents protecting public
      safety: Regulations should be implemented at a federal level to require basic
      levels of standardization and quality control in the manufacture of herbal
      products. Indexing terms in medical bibliographic systems should be expanded to
      target herbal products. Funding should be increased for scientific research
      evaluating herbal products. Pharmacy schools should include a competency
      statement in their curricula regarding herbal medicines. Continuing education in
      herbal products should be available and encouraged for all pharmacists.
      Pharmacists should approach the use of all therapeutic interventions with
      scientific rigor, whether they are traditional or complementary in nature.
      Patients will benefit as more information is known and widely disseminated. By
      actively embracing the responsibility for counseling individuals on the
      appropriate use of herbal products, pharmacists will become a recognized source
      of expert information in this rapidly growing area, yielding important
      improvements in the quality of care.

PMID- 10907986
TI  - Are thyroidologists in danger of substituting movement for thought?

PMID- 10907987
TI  - Polymorphism in the promoter and exon 1 of the cytotoxic T lymphocyte antigen-4
      gene associated with autoimmune thyroid disease in Koreans.
AB  - The objective of this study was to examine the polymorphism in the cytotoxic T
      lymphocyte antigen-4 (CTLA-4) gene and its relationship with autoimmune thyroid
      disease in Koreans. Polymorphism in the promoter and exon 1 of CTLA-4, clinical
      symptoms of disease and thyrotropin receptor antibody (TSHRAb) characteristics
      were analyzed. Polymorphism was detected using restriction fragment length
      polymorphism and polymerase chain reaction amplification of genomic DNA. All
      subjects were Korean (97 Graves' disease, 110 Hashimoto's thyroiditis, and 199
      normal controls). Graves' patients had significantly more G allele in exon 1 and
      C allele in the promoter than controls. When the exon 1 genotype was GG, the
      frequency of CC genotype in the promoter was higher. Allele frequencies in CTLA-4
      did not differ from controls in patients with Hashimoto's thyroiditis. In Graves'
      patients, there were significant differences between genotypic groups in serum
      triiodothyronine (T3) levels and the presence of ophthalmopathy. However, TSHRAbs
      and other clinical characteristics were not significantly different. In
      conclusion, the CTLA-4 G allele in exon 1 and C allele in the promoter may confer
      genetic susceptibility to Graves' disease in Koreans. These two polymorphisms are
      additional and dependent genetic risk markers that help to characterize risk
      alleles within CTLA-4 gene.

PMID- 10907988
TI  - Megalin-mediated transcytosis of thyroglobulin by thyroid cells is a calmodulin
      dependent process.
AB  - Megalin, a multiligand receptor expressed on the apical surface of thyroid cells,
      mediates transepithelial transport (transcytosis) of thyroglobulin (Tg) across
      thyrocytes, resulting in diversion of Tg from the lysosomal pathway and reduction
      of the extent of thyroid hormone release from internalized Tg molecules. The
      calcium regulatory protein calmodulin facilitates some forms of transcytosis.
      Here we investigated the role of calmodulin in megalin-mediated transcytosis of
      Tg by thyroid cells. For this purpose, we studied the effect of calmodulin
      antagonists on Tg transcytosis by Fisher rat thyroid cells (FRTL-5), an
      established, differentiated thyroid cell line. FRTL-5 cells were cultured on
      permeable filters in the upper chamber of dual chambered devices, with megalin
      expression exclusively on the upper surface. Unlabeled Tg was added to the upper
      chamber at 37 degrees C, and transcytosed Tg was detected by enzyme-linked
      immunosorbent assay (ELISA) in fluids collected 1 hour later from the lower
      chamber. To study the role of calmodulin in Tg transcytosis, cells were
      preincubated with one of two calmodulin antagonists, either trifluoperazine or
      W7. Both antagonists markedly reduced transcytosis of Tg by FRTL-5 cells. These
      inhibitory effects and those of a monoclonal antimegalin antibody were not
      additive, indicating that calmodulin acts on the megalin-mediated pathway.
      Furthermore, trifluoperazine increased the extent of triiodothyronine (T3)
      release from exogenously added Tg by FRTL-5 cells, indicating that Tg transported
      in the calmodulin-dependent, megalin-mediated pathway, bypasses the lysosomal
      pathway.

PMID- 10907989
TI  - A novel V59E missense mutation in the sodium iodide symporter gene in a family
      with iodide transport defect.
AB  - Iodide transport defect results from the malfunction of iodide transporter
      (sodium iodide symporter [NIS]), and is characterized by low uptake of iodide
      into thyroid cells. Genetic analysis revealed that a T354P missense mutation
      causes iodide transport defect in the homozygous state and is a frequent mutation
      in the Japanese population. We recently reported three siblings with iodide
      transport defect harboring the T354P mutation in the heterozygous state. Here we
      report a novel V59E missense mutation associated with these siblings. The mutant
      protein showed low iodide transport activity.

PMID- 10907990
TI  - Vitamin D receptor initiation codon polymorphism in Japanese patients with
      Graves' disease.
AB  - Recent studies have shown that related genetic influences on bone mineral density
      (BMD) and bone turnover are related to allelic variations in the vitamin D
      receptor (VDR) gene. Osteoporosis as a complication of hyperthyroidism is
      characterized by increased rates of both bone formation and bone resorption. In
      addition, VDR gene polymorphism influences susceptibility to some autoimmune
      diseases such as insulin-dependent diabetes mellitus (IDDM) and multiple
      sclerosis (MS). In the gene encoding the VDR, we investigated the distribution of
      a VDR-FokI polymorphism that changes the predicted protein sequence. The subjects
      were 131 female Japanese patients with Graves' disease and 150 female controls.
      The distribution of genotype frequencies differs between Graves' disease and
      controls (chi2 = 5.99, degrees of freedom = 2, p = 0.0386). We found
      overexpression of F allele (69% vs. 61%, p = 0.0472) and homozygote FF (48% vs.
      33%, p = 0.0118) in Graves' disease patients compared with controls. We also
      correlated a VDR-FokI polymorphism with BMD in the distal radius and biochemical
      markers of bone turnover in patients with Graves' disease in remission. Although
      generally, no significant association was seen between age-adjusted BMD and
      genotype, patients in remission for fewer than 5 years showed significantly lower
      age-adjusted BMD in Ff heterozygotes than in ff homozygotes (z = 1.14 ff vs. z = 
      0.43 Ff, p < 0.05). Moreover, serum concentrations of bone alkaline phosphatase
      were significantly greater in Ff homozygotes than in FF homozygotes (78 +/- 12
      vs. 59 +/- 10, p < 0.05). The genotypes did not differ in serum concentrations of
      osteocalcin, urinary hydroxyproline, or urinary deoxypyridinoline. Our results
      indicate, for the first time, an association between Graves' disease and a VDR
      polymorphism in the Japanese and suggest that a VDR-FokI polymorphism may affect
      bone mineral metabolism and can predict risk of osteoporosis as a complication of
      Graves' disease in patients in remission.

PMID- 10907992
TI  - Is repeated fine-needle aspiration cytology useful in the management of patients
      with benign nodular thyroid disease?
AB  - Management of nonneoplastic thyroid nodules (TN) diagnosed by fine-needle
      aspiration (FNA) is controversial. While clinical follow-up with repeat FNA for
      enlarging TN is recommended in some studies, others recommend repeat FNA in
      follow-up of all benign TN after several months or years, in order to identify
      possible misdiagnosed malignant lesions. This study was done to determine the
      usefulness of repeat FNA in patients with benign nodular thyroid disease. We
      studied 94 fine-needle reaspirations performed on 43 females and 2 males 48.2 +/-
      17 years of age with benign nodular thyroid nodular disease. Four patients had 3
      consecutive FNAs and 41 patients had 2 consecutive FNAs. All FNAs were carried
      out by the same endocrinologist in the same thyroid area or by cytopathologists.
      The average time elapsed between the two consecutive FNAs was 18.3 +/- 11.2
      (range, 4-48) months. Of the 45 patients, 23 presented with increase in size of
      the nodule and the remaining 22 patients did not have any change in size at the
      time of repeat FNA. Identical cytologic diagnoses were rendered in 39 of the 45
      patients who underwent 2 or 3 consecutive FNA. Repeat FNA did not result in
      detection of any malignant neoplasms. Thyroid resection in 7 patients with
      increased nodule size and pressure symptoms confirmed the cytologic impressions
      of benign thyroid nodular disease. Our results show that the routine performance
      of repeated FNA cytology in the follow-up of patients with benign nodular thyroid
      disease with or without any clinical changes is of limited usefulness. Clinical
      factors rather than repeat FNA may hold precedence in surgical management of
      patients with benign nodular thyroid disease.

PMID- 10907991
TI  - Thyroid organoid formation in simulated microgravity: influence of keratinocyte
      growth factor.
AB  - The generation of artificial human thyroid tissues in suspension (low-shear
      environment, present in simulated microgravity [MG] and generated by a rotary
      cell culture system [RCCS]), was enhanced by increasing medium kinematic
      viscosity with a (3% v/v) suspension of extracellular matrix (basement membrane
      extract [BME]) in serum-free medium to generate artificial human thyroid
      organoids. Recombinant human keratinocyte growth factor (KGF, 7 ng/mL)
      facilitated human thyrocyte aggregation and three-dimensional (3-D)
      differentiation. There was an MG-associated decrease in extractable DNA that was
      reversed after addition of keratinocyte growth factor (KGF). In simulated MG, the
      increase in extractable DNA after KGF addition was up to 170% over non-KGF
      control cultures. In contrast, monolayer cultures in unit gravity showed a
      maximum DNA increase of 39% after KGF addition. Morphologically, differentiated
      thyroid neofollicles displayed polarization and were located in close proximity
      after 2 weeks of culture. Immunogold labeling with antibody to human
      thyroglobulin (Tg) revealed staining of follicular lumina and secretory vesicles,
      and a time-dependent increase in human Tg was detected in the culture media.
      Culture under simulated MG thus allowed direct visualization of KGF-facilitated
      thyrocyte/extracellular matrix interaction. Such artificial human thyroid
      organoids-generated in MG and in the presence of KGF-structurally resembled
      natural thyroid tissue. The above findings may have implications for autoimmune
      thyroid disease where KGF (if, for example, secreted locally by intraepithelial
      gammadelta T cells among other cells) may contribute to thyroid cell growth.

PMID- 10907993
TI  - The effect of iodine administration on the development of thyroid autoimmunity in
      patients with nontoxic goiter.
AB  - OBJECTIVE: Previous studies, mostly performed in iodine-deficient areas, have
      suggested that the administration of iodine to patients with endemic goiter may
      be associated with the development of thyroid autoantibodies (ThAbs); however,
      this has not been a consistent finding. In this study, we evaluated the effect of
      iodine on thyroid function and on the development of indices of autoimmunity
      (ThAbs and lymphocytic infiltration) in an iodine replete area. METHODS: Iodized
      oil (1 mL) was administered intramuscularly to 40 euthyroid patients with
      nontoxic goiter, adequate iodine intake, and absent or normal levels of ThAbs.
      Blood and urinary samples were taken at time 0, 3, 6, and 12 months after iodine
      administration. Thyroid volume was evaluated and fine-needle aspiration (FNA) was
      performed at 0, 6, and 12 months. RESULTS: Seven patients developed abnormal
      levels of ThAbs at some time between 3 and 12 months after iodine administration
      (p = 0.017). Mean anti-thyroglobulin (Tg) antibody levels increased at 6 months
      without reaching abnormal levels, but did not reach statistical significance (p =
      0.062). Lymphocytic infiltration was detected in FNA smears in 10 cases before
      and in 27 cases after treatment (p = 0.0003). Triiodothyronine (T3) decreased at
      12 months of follow-up, while thyroxine (T4) and thyrotropin (TSH) levels did not
      change significantly. A decrease in the mean levels of thyroglobulin as well as a
      small reduction in goiter size was observed at 6 and 12 months. CONCLUSION: The
      administration of iodized oil to patients with small nontoxic goiter in an iodine
      replete area was accompanied by the development of abnormal levels of ThAbs in
      some cases and by an increase in thyroid lymphocytic infiltration.

PMID- 10907994
TI  - Thyroid function in children with perinatal human immunodeficiency virus type 1
      infection.
AB  - OBJECTIVE: To study thyroid function in children with perinatal HIV-1 infection
      retrospectively and determine whether thyroid abnormalities are correlated with
      clinical condition, disease progression, immunological impairment, and viral
      load. STUDY DESIGN AND SETTING: Total (TT4) and free (FT4) thyroxine, total (TT3)
      and free (FT3) triiodothyronine, reverse triiodothyronine (rT3), thyrotropin
      (TSH), thyroglobulin (TG), and thyroid binding globulin (TBG) were measured twice
      in 56 children with perinatal human immunodeficiency virus type 1 (HIV-1)
      infection. Median age at first determination was 13.5 (range: 0.03-127.0) months;
      median age at second determination was 66.2 (range 3.42-147.4) months.
      Antithyroglobulin, antimicrosomal, thyroid peroxidase, and thyrotropin receptor
      antibodies were also evaluated. Fifty-three healthy children were selected as
      controls. RESULTS: TT3, TT4, FT4, and TG were significantly reduced and rT3, TBG,
      and TSH increased in children with HIV-1 infection when compared with controls.
      Thyroid dysfunction correlated with severe immunosuppression and high viral load
      early in life preceded the onset of the disease and worsened over time.
      Autoantibodies were negative in all children with HIV-1 infection in all
      determinations. CONCLUSION: Thyroid abnormalities are observed early in the
      course of perinatal HIV-1 infection; thyroid dysfunction is particularly
      pronounced in children with severe immunosuppression and high viral load.
      Modifications of thyroid function precede worsening of clinical course in HIV-1
      infected children.

PMID- 10907995
TI  - Primary thyroid lymphoma: diagnosis of immunoglobulin heavy chain gene
      rearrangement with polymerase chain reaction in ultrasound-guided fine-needle
      aspiration.
AB  - We present a case of primary thyroid lymphoma coexisting with Hashimoto's
      thyroiditis in a 75-year-old woman in whom B-cell lymphoma was substantiated
      based on the findings of immunophenotyping and polymerase chain reaction (PCR)
      gene rearrangement in specimens that had been obtained by ultrasound (US)-guided
      fine-needle aspiration biopsy (FNAB). The immunophenotyping technique showed A
      light chain restriction, and PCR-based assays showed a discrete narrow band,
      which was diagnostic for clonal B-cell proliferation. Analyses of PCR gene
      rearrangement in US-guided FNAB may be a useful ancillary technique to
      pathological findings for diagnosis of primary thyroid lymphoma, especially for
      differentiation between low-grade B-cell lymphomas and Hashimoto's thyroiditis.

PMID- 10907996
TI  - Ectopic lingual thyroid: an otolaryngologic emergency beyond childhood.
AB  - Ectopic thyroid is rare and occasionally presents suddenly in childhood. Adult
      patients with thyroid ectopy who develop local symptoms commonly have an enlarged
      ectopic gland and hypothyroidism. We describe the first case of an adult patient
      who sudden presented with sudden dysphagia and dyspnea caused by a large lingual
      thyroid in clinical and biochemical euthyroidism. Treatment consisted of surgical
      removal of the ectopic gland and thyroid hormone replacement therapy.

PMID- 10907997
TI  - How much radioiodine should you give?

PMID- 10907998
TI  - Air in the thyroid.

PMID- 10907999
TI  - Fatal liver failure after high-dose glucocorticoid pulse therapy in a patient
      with severe thyroid eye disease.

PMID- 10908000
TI  - History of the methamphetamine problem.
AB  - Methamphetamine, called meth, crystal, or speed, is a central nervous system
      stimulant that can be injected, smoked, snorted, or ingested orally; prolonged
      use at high levels results in dependence. Methamphetamine (MA) is a derivative of
      amphetamine, which was widely prescribed in the 1950s and 1960s as a medication
      for depression and obesity, reaching a peak of 31 million prescriptions in the
      United States in 1967. Until the late 1980s, illicit use and manufacture of MA
      was endemic to California, but the MA user population has recently broadened in
      nature and in regional distribution, with increased use occurring in midwestern
      states. An estimated 4.7 million Americans (2.1% of the U.S. population) have
      tried MA at some time in their lives. Short- and long-term health effects of MA
      use include stroke, cardiac arrhythmia, stomach cramps, shaking, anxiety,
      insomnia, paranoia, hallucinations, and structural changes to the brain. Children
      of MA abusers are at risk of neglect and abuse, and the use of MA by pregnant
      women can cause growth retardation, premature birth, and developmental disorders
      in neonates and enduring cognitive deficits in children. MA-related deaths and
      admissions to hospital emergency rooms are increasing. Although inpatient
      hospitalization may be indicated to treat severe cases of long-term MA
      dependence, optimum treatment for MA abusers relies on an intensive outpatient
      setting with three to five visits per week of comprehensive counseling for at
      least the first three months. The burgeoning problems of increased MA use must be
      addressed by adequate treatment programs suitable for a variety of user types.

PMID- 10908001
TI  - A multisite study of the effectiveness of methamphetamine treatment: an
      initiative of the Center for Substance Abuse Treatment.
AB  - In 1998, responding to national and regional epidemiological data indicating that
      methamphetamine (MA) abuse was a growing problem in the United States, the Center
      for Substance Abuse Treatment (CSAT) initiated a multisite MA treatment study.
      Through a collaborative approach among CSAT, seven treatment sites, and a
      coordinating center, the study compares the clinical and cost effectiveness of a
      manualized, cognitive-behavioral outpatient treatment developed by the Matrix
      Center in Los Angeles to the treatment approaches currently employed by the
      treatment sites. The study also explores technology transfer issues associated
      with integrating the Matrix approach within existing treatment settings. CSAT's
      approach to the initiation and management of this type of study is discussed.

PMID- 10908002
TI  - The CSAT methamphetamine treatment program: research design accommodations for
      "real world" application.
AB  - The Methamphetamine Treatment Program (MTP), funded by the Center for Substance
      Abuse Treatment, has the objectives of implementing the Matrix outpatient model
      and evaluating that model in comparison to the existing community "treatments as
      usual." Seven organizations in three western states (California, Montana, and
      Hawaii) were selected to participate in this randomized, controlled, multisite
      project in what constitutes the largest trial to date of treatment for
      methamphetamine (MA) dependence. One hundred fifty MA-dependent patients
      recruited at each site are randomly assigned to receive either the Matrix model,
      a manualized program of intensive outpatient treatment, or the site's standard
      treatment, "treatment as usual." Participants are evaluated at admission, weekly
      during treatment, at the time of scheduled discharge, and at six and 12 months
      after admission. Dependent measures assess changes in drug use, HIV risk
      behaviors, quality of life, and patient satisfaction. Cost analyses to quantify
      treatment costs and determine the association between costs and clinical outcomes
      will be conducted. A number of adjustments in the original study design have been
      necessitated by the realities of community sites' strengths and limitations.
      Experiences from this multisite project will also provide a model for other
      efforts to transfer research-based treatments into community settings. This
      article describes the main aims of the project, the background and rationale for
      the study design, a brief description of the research plan, and methods
      implemented to protect the integrity of the science.

PMID- 10908003
TI  - The matrix model of outpatient stimulant abuse treatment: history and
      description.
AB  - The Matrix model was originally developed in response to the cocaine epidemic of
      the 1980s. The program consists of relapse prevention groups, education groups,
      social support groups, individual counseling, and urine and breath testing
      delivered in a structured manner over a 16-week period. The treatment is a
      directive, nonconfrontational approach which focuses on current issues and
      behavior change. Several evaluations of the model have supported its usefulness
      and efficacy with methamphetamine (MA) users. Methamphetamine users appear to
      respond to treatment similarly to cocaine users and many continue to show
      improvements at follow-up.

PMID- 10908004
TI  - Treatment-as-usual in the methamphetamine treatment project.
AB  - The Methamphetamine Treatment Project is a multisite trial that compares the
      effectiveness of eight models of outpatient treatment for methamphetamine
      dependence to that of the Matrix model. These eight "treatment-as-usual" models
      represent diverse approaches developed in a variety of settings to serve markedly
      different populations. The theoretical foundations of these treatments are
      described as well as the settings in which they are delivered. To facilitate
      comparisons, details are presented with respect to frequency of group and
      individual sessions, duration of treatment, therapist qualifications, and access
      to ancillary services. The populations served by these programs vary with respect
      to race and ethnicity. Most programs serve primarily non-Hispanic Caucasians, but
      some programs serve significant proportions of Hispanics, Asians, Pacific
      Islanders, and Native Americans. Usual route of administration of methamphetamine
      also varies by site, with snorting, smoking, and injecting each reported as the
      most common route of administration at one or more sites. The Minnesota model and
      cognitive-behavioral approaches are most commonly used in these programs,
      although contingency management and psychodynamic approaches are also
      represented. The intensive phase of treatment ranges between four and 24 weeks;
      the number of hours per week of client contact varies between one and 13. This
      trial will provide the opportunity to test the effectiveness of a wide range of
      treatments currently in use in community settings.

PMID- 10908005
TI  - Methamphetamine abuse: issues for special populations.
AB  - Methamphetamine (MA) abuse has been a problem in the western United States for
      decades. However, recently the incidence of MA abuse has risen to epidemic levels
      in some regions and among particular subgroups of the population. Recognizing the
      need to develop effective treatments for MA dependence, the Center for Substance
      Abuse Treatment (CSAT) established a multisite Methamphetamine Treatment Program
      (MTP) that compares the Matrix Model treatment program for MA to the treatments
      as usual at seven community-based clinics in California, Montana and Hawaii.
      Examination of the clients receiving services though this project provides an
      opportunity to explore particular issues of diverse special populations who are
      impacted by the problem of MA dependence. These groups include rural Americans,
      Native Americans, Hawaiians, gay and bisexual males and drug court participants.
      Specifically, this article examines cultural, geographic and situational barriers
      to accessing and completing treatment and presents strategies that have been used
      to overcome these barriers.

PMID- 10908006
TI  - A descriptive analysis of participant characteristics and patterns of substance
      use in the CSAT methamphetamine treatment project: the first six months.
AB  - The CSAT Methamphetamine Treatment Project (MTP) is a multisite study with a two
      fold purpose: to assess the feasibility and outcomes generated by a technology
      transfer of the Matrix treatment model for methamphetamine (MA) abuse into
      several community-based treatment programs, and specifically to compare outcomes
      of treatment as usual at each site with outcomes of the Matrix model, as
      implemented in each site. The study comprises seven sites, geographically
      situated in Hawaii, Northern and Southern California, and Montana. This article
      presents a demographic description of the cohort, and describes patterns of drug
      use, abuse, and related problems among the 169 participants recruited in the
      first six months of the study, from April through September 1999. Specific
      analyses presented include: demographic composition of the sample with respect to
      gender, age, ethnicity, education completed, employment status, and income;
      primary drug used, and mean percent of days using various drugs including MA,
      alcohol, and marijuana; and percent of sample reporting various routes of drug
      administration. Mean baseline Addiction Severity Index composite scores are
      presented that describe medical, employment, alcohol, drug, legal, family/social,
      and psychiatric status for the sample. Also presented here are comparisons of
      this preliminary population to other populations reported in the literature. This
      early subset of MTP participants is similar to other methamphetamine-abusing
      populations described in the literature in age, years of education, income, and
      mean years of use. However, because of its multisite structure and the locations
      of its constituent sites, the MTP population has greater variation in ethnic
      makeup than do populations from other studies, offering an opportunity to provide
      useful new information about drug use patterns and treatment responses in
      populations not previously studied.

PMID- 10908007
TI  - Conducting trials in community settings: the provider perspective.
AB  - Providers and their treatment programs are the focus of efforts to translate
      research into practice. In the best of partnerships, they are more than the
      recipients of research efforts, because they are actively involved in developing
      and evaluating healthy links between practice and research . This article reports
      on experiences in a multisite methamphetamine treatment trial funded in October
      of 1998 by the Center for Substance Abuse Treatment. The goal of the trial is to
      generate knowledge about how a comprehensive treatment protocol developed by the
      Matrix Center in Los Angeles can be effectively transferred to the community drug
      treatment system. The Matrix model provides a three-times-per-week outpatient
      treatment experience that combines behavioral, educational, and 12-Step
      counseling techniques. When complete, the study will compare outcomes of the 16
      week Matrix program with the usual treatment offered by the programs at the eight
      participating sites. The UCLA Drug Abuse Research Center and the Matrix Institute
      on Addictions coordinate the trial. This article describes factors that have
      fostered or hindered the development of this partnership. These factors can be
      divided into three temporal phases, although the circumstances presented may
      occur at any time during the research process. The first set of factors affecting
      the development of a healthy research-to-practice relationship exists prior to
      the establishment of that relationship. A second set of circumstances occurs at
      the initiation of the collaborative enterprise, and the third set of factors is
      more involved in the development and maintenance of ongoing productive
      collaboration between researchers and providers.

PMID- 10908010
TI  - Predictors of relapse after treatment for methamphetamine use.
AB  - The purpose of this study is to describe treatment utilization and relapse and
      examine possible predictors of time to relapse after treatment for
      methamphetamine (MA) use. This analysis is based on natural history interview
      data from 98 subjects treated for MA use in publicly-funded programs in Los
      Angeles County in 1995-97 and interviewed two to three years following their
      treatment admission. Results showed that half of the subjects had resumed MA use:
      36% within six months of the end of treatment, and 15% more within seven to 19
      months. Survival analysis methods showed significant predictors of (shorter) time
      to relapse were shorter length of treatment, older age of first substance use,
      and involvement in selling MA; ethnicity (being Hispanic) and more previous time
      in treatment had weaker effects.

PMID- 10908008
TI  - Moving research into community settings in the CSAT methamphetamine treatment
      project: the coordinating center perspective.
AB  - The CSAT Methamphetamine Treatment Project (MTP) has been established to conduct
      a ground-breaking exercise in bringing research into a closer relationship with
      community-based treatment service organizations. In this article, some of the
      opportunities and challenges faced by the MTP coordinating center as it has
      attempted to bring research into community treatment organizations are described.
      Initially, there has been an active, energetic effort to design the study
      protocol, focus the activities of the project, and prioritize the tasks to be
      accomplished. The methods for training the research staff and monitoring the
      conduct of the research in the community sites are described. A number of
      observations have been made about the different "cultures and values" of the
      researchers and the seven clinical organizations where the project has been
      conducted. The myriad mistakes made and lessons learned about how to conduct a
      rigorous randomized clinical trial in community treatment organizations may be
      important for future research-treatment efforts. There has been a wealth of
      experience gained in the first year of this project that may be of use as efforts
      move forward to reduce the gap between research and practice.

PMID- 10908011
TI  - Correlates of outpatient drug treatment drop-out among methamphetamine users.
AB  - This article explores correlates of retention among the 2.337 methamphetamine
      (MA) users entering public outpatient treatment programs in California from
      January 1, 1994 through September 30, 1997. A secondary analysis of data from the
      California Alcohol and Drug Data System (CADDS) was performed and predictors of
      drop-out before treatment completion (as measured by a retention of 180 days or
      more) were determined using logistic regression. Overall, 23.3% of MA users
      completed treatment, a rate similar to that for users of other drugs throughout
      California. As expected, MA users who were older (40 years or over), had less
      severe drug use patterns (used less than daily or did not inject), or who were
      under coerced treatment were significantly more likely to complete treatment that
      other MA users. Surprisingly, men were significantly more likely than women to
      drop out of treatment before 180 days. Until studies currently collecting primary
      data on MA treatment are completed, the present secondary analysis provides a
      useful foundation upon which future research and intervention strategies may be
      based.

PMID- 10908009
TI  - The CSAT methamphetamine treatment project: what are we trying to accomplish?

PMID- 10908012
TI  - A comparison of injecting and noninjecting methamphetamine users.
AB  - The injection of illicit drugs exposes the user to a variety of risks that are
      not associated with other routes of administration. Information regarding
      differences between injecting and noninjecting methamphetamine (MA) users is
      provided. The population studied included MA dependent men and women (n = 427)
      from the Matrix Institute on Addictions in San Bernardino County, California. The
      sample was divided into two groups according to their injecting status; 55
      individuals (13%) reported injecting, and 372 (87%) reported no history of
      injecting MA. Differences were found in specific use patterns and in medical,
      criminal, and psychological histories between the two groups.

PMID- 10908013
TI  - Methamphetamine and cocaine users: differences in characteristics and treatment
      retention.
AB  - The use of methamphetamine and cocaine have both produced significant public
      health problems during the past two decades. Although these powerful
      psychostimulants have many common acute and chronic effects, there are some
      important differences in who uses these drugs and the consequences of their use.
      This article reports on two large cohorts of treatment-seeking cocaine and
      methamphetamine users who entered treatment at the same facility over the same
      four-year period of time. Patterns of use differed significantly. Cocaine users
      have more episodic use patterns, spend more money on purchasing their drugs, and
      use alcohol more heavily. Methamphetamine users include a higher proportion of
      women, more frequently use on a daily basis, use marijuana more often, and
      experience more severe medical and psychiatric consequences. Despite the
      differences in the stimulant drug effects and consequences, the treatment
      response to a multicomponent, outpatient program is very similar.

PMID- 10908014
TI  - Glycopeptide resistance in Staphylococcus aureus.

PMID- 10908015
TI  - Influenza virus: a master of metamorphosis.
AB  - Novel influenza viruses continuously emerge in the human population. Three times
      during the present century, an avian influenza virus subtype crossed the species
      barrier, starting a pandemic, and establishing itself for one to several decades
      in man. As the 1997 H5N1 event in Hong Kong indicated, the occurrence of another
      pandemic in the near future cannot be excluded. Sufficient vaccine may not be
      available to ameliorate the consequences of such an event, because of a shortage
      of time. During interpandemic periods, important antigenic drift variants
      sometimes arise at a point of time when, with the current state of the technique,
      production of a correspondingly adapted vaccine is also impossible. We may be
      able to solve these problems by increasing influenza surveillance and by adopting
      new ways of vaccine composition, production, formulation, presentation, and
      delivery. The recently developed anti-neuraminidase antivirals should only be
      considered as (valuable) adjuncts to vaccines.

PMID- 10908016
TI  - Systemic lupus erythematosus--is a viral aetiology a credible hypothesis?

PMID- 10908017
TI  - The disease burden of hepatitis B in Uzbekistan.
AB  - OBJECTIVE: To describe the burden of hepatitis B illness in Uzbekistan by means
      of model-based estimates. METHODS: A mathematical simulation model was developed
      to mimic the disease evolution of hepatitis B and calculate the size and age of
      specific HBV patient groups, defined according to the severity of their illness.
      RESULTS: The calculations indicate that of 678000 neonates in Uzbekistan, 159185
      (235 per 1000) would incur an HBV infection at some time during their lives.
      About 55095 persons (81 per 1000) would become chronic carriers of hepatitis B
      and 6307 persons (9.3 per 1000) are expected to die due to hepatitis B before
      they would die from another cause. In the overall population, we calculated that
      about 3074 Uzbeki die each year from the consequences of hepatitis B. Only 3.2%
      of these premature HBV-deaths are due to acute hepatitis B, whereas 96.8% are due
      to chronic hepatitis B. It was calculated that 2.1% of all deaths (or 1 in 47
      deaths), and nearly 25% of deaths (or one in four deaths) between 30 and 40 years
      of age in Uzbekistan are due to hepatitis B. Vaccination seems easily defensible
      on the basis of rudimentary but very conservative cost-effectiveness calculations
      ($84 per carrier prevented; $735 per death prevented and $22 per life-year
      gained). CONCLUSION: Hepatitis B represents a huge health problem in Uzbekistan,
      especially in young adults. The potential for prevention by vaccination seems
      very high, but demands a long-term vision if chronic hepatitis, in particular, is
      to be reduced. Routine hepatitis B vaccination was found to be a relatively cost
      effective intervention in Uzbekistan.

PMID- 10908018
TI  - Human herpesvirus type 8 in HIV-infected patients with interstitial pneumonitis.
AB  - OBJECTIVES: The new human herpesvirus type 8 (HHV-8) has been detected in all
      types of Kaposi's sarcomas, as well as in body-cavity lymphomas and Castleman's
      disease. Recently, HHV-8 has also been associated with encephalitis in HIV
      positive and HIV-negative patients. Interstitial pneumonitis, combined with
      detection of HHV-8 in non HIV-infected patients, indicates a pathogenetic role of
      HHV-8 in unexplained lung diseases. We have studied two HIV-infected patients,
      with otherwise unexplained interstitial pneumonitis for the presence of HHV-8.
      METHODS: Lung biopsies of both patients were investigated for HHV-8 sequences. A
      nested PCR method was used for amplification of HHV-8 DNA fragments, and the
      nature of the amplification products was confirmed by Southern blot
      hybridization. In addition, we used an in situ hybridization technique and
      immunohistochemical staining for detection of HHV-8 infected cells. RESULTS:
      Amplification of HHV-8 DNA fragments was seen with template DNA from lung
      biopsies of both cases and the appropriate positive controls, but not with
      negative controls. In situ hybridization and immunohistochemical staining
      demonstrated HHV-8 infected lymphoid cells and alveolar macrophages in both
      patients as well. CONCLUSIONS: HHV-8 was found in HIV-infected patients with
      otherwise unexplained interstitial pneumonitis, but the pathogenic role of HHV-8
      in patients with interstitial pneumonia remains unclear.

PMID- 10908019
TI  - Acute pyogenic iliopsoas abscess in Taiwan: clinical features, diagnosis,
      treatments and outcome.
AB  - OBJECTIVES: To study the variations of aetiology in the patients with acute
      pyogenic iliopsoas abscess and identify the appropriate diagnostic modalities as
      well as therapeutic alternatives (e.g. extraperitoneal or retrofascial
      percutaneous catheter drainage, PCD) other than surgery. METHODS: We carried out
      a retrospective review and analysis of 25 patients with acute pyogenic iliopsoas
      abscess in our institution from August 1988 to July 1998. Blood and urine
      cultures, imaging studies of the plain films of the abdomen (KUB),
      ultrasonography (echo) and computed tomography (CT scan) were performed in all
      patients. The therapeutic regimens included antibiotics only, PCD or aspiration,
      and surgery. RESULTS: The male to female ratio was 7: 18. The mean age was 64
      years old. Diabetes mellitus (64%) was the dominant predisposing or associated
      factor. The most common aetiological source was urinary tract infection (52%)
      with enteric micro-organisms (Escherichia coli: 44% and Klebsiella spp.: 24%).
      Nineteen patients (76%) had pain in the abdomen, flank or back. Six cases (24%)
      were classified as 'primary' abscess, and only two patients survived. Nine cases
      were treated with antibiotics alone, only four responded and the others expired.
      Of the 15 cases receiving PCD or aspiration, five cases received subsequent
      surgical drainage or nephrectomy and survived. Another one case of Clostridia gas
      gangrene received emergency fasciotomy and expired. The total mortality was
      extremely high (11/25, 44%). CONCLUSIONS: We concluded that: (i) the aetiology of
      iliopsoas abscess may vary with the country of origin, with a preponderance of
      urinary tract infection in our Taiwanese series; (ii) a high index of suspicion
      is mandatory to enable early diagnosis of acute pyogenic iliopsoas abscess,
      particularly for older diabetic patients with fever, pain in the abdomen or
      flank, limp or flexion of the ipsilateral hip; (iii) CT scan can confirm the
      diagnosis and define the extent of the abscess; (iv) effective management should
      include appropriate antibiotic therapy and drainage of the abscess; (v) image
      guided PCD should be tried first because of its low morbidity. However, should it
      fail, subsequent surgical drainage should be performed.

PMID- 10908020
TI  - Early predictors of mortality in pneumococcal bacteraemia.
AB  - OBJECTIVES: Pneumococcal bacteraemia carries a mortality of about 20%.
      Approximately 50% of deaths from pneumococcal bacteraemia occur within the first
      48 h of admission. In order to influence outcome, critically ill patients should
      be identified at the time of presentation. This study enables the clinician to
      rapidly make an evidence-based assessment of a patient's prognosis, allowing the
      identification of patients who should be placed in a high-risk category at an
      early stage, when appropriate management is most likely to be effective. METHODS:
      Data were collected from the medical record of history, physical examination,
      radiological examination and laboratory investigations done on initial
      presentation using a standardized proforma. The data were first examined by
      Pearson's Chi-squared test, with Yates' correction if needed. Variables found to
      be significantly associated with case fatality ( P < 0.05) by these methods were
      examined by stepwise logistic regression analysis in order to identify those
      factors which were independent predictors of case fatality. RESULTS: The overall
      case fatality was 21%. Older age, apyrexia, tachypnoea, bilateral consolidation,
      hypoalbuminaemia, elevated aminotransferases, renal impairment, acidosis and
      leucopaenia were significantly associated with higher case fatality. Older age,
      acidosis and elevated serum alanine aminotransferase (ALT) were independent
      predictors of case fatality. Fifty-five percent of isolates belonged to serotypes
      4, 6B, 9V, 14, 19F and 23F, to which good antibody levels have been documented in
      both young and elderly patients post-vaccination. Serotype 14 was most common,
      and was significantly associated with higher case fatality. Colder weather was
      associated with a higher incidence of both infection and case fatality. The case
      fatality amongst patients receiving ITU management was 44%. Less than 50% of
      patients who died received ITU management. CONCLUSIONS: Despite the increased
      availability of new antibiotics and vaccines, the mortality of patients with
      pneumococcal bacteraemia remains unchanged. The parameters above allow early
      identification of patients with a higher case fatality; these patients may
      benefit from being placed in a "high-risk" category early on in their management.
      Vaccination of the elderly may reduce the incidence and/or mortality from
      pneumococcal bacteraemia. Further studies are required to understand the reasons
      for referral for intensive therapy in acute pneumococcal bacteraemia and whether
      ITU management affects outcome.

PMID- 10908021
TI  - A novel serological test for the diagnosis of central venous catheter-associated
      sepsis.
AB  - OBJECTIVES: To determine the sensitivity and specificity of a novel antibody test
      for the diagnosis of intravascular catheter-related infections due to coagulase
      negative staphylococci. METHODS: Sixty-seven patients diagnosed as having central
      venous catheter (CVC)-associated sepsis based on strict clinical criteria,
      including positive blood cultures, were compared to 67 patients with a CVC in
      situ who exhibited no evidence of sepsis. An ELISA serological test based on a
      novel short-chain lipoteichoic acid antigen isolated from coagulase-negative
      staphylococci (CNS) was used to determine the patient's serological response (IgG
      and IgM) to CVC sepsis caused by CNS. The specificity and sensitivity of the test
      was determined. RESULTS: There was a significant increase in the antibody levels
      (IgG and IgM) to the short-chain lipoteichoic acid in patients with CVC
      associated staphylococcal sepsis as compared to the control patients.
      CONCLUSIONS: This new serological method may offer a useful diagnostic test for
      intravascular catheter infections caused by staphylococci.

PMID- 10908022
TI  - Clinical features and therapeutic implications of 104 episodes of monomicrobial
      Aeromonas bacteraemia.
AB  - OBJECTIVES: Aeromonas bacteraemia is not a common infectious disease, but can
      cause a grave outcome in infected cases. In this study, clinical presentations
      and prognostic factors of cases of monomicrobial Aeromonas bacteraemia were
      analysed. Also, the impact of beta-lactam and aminoglycoside in combination and
      of emerging cephalosporin-resistance during therapy was discussed. METHODS: From
      1989 to 1998 in a medical centre in southern Taiwan, those cases with
      monomicrobial Aeromonas bacteraemia were included for study. RESULTS: A total of
      104 episodes of monomicrobial Aeromonas bacteraemia, accounting for 74% of all
      Aeromonas bacteraemia, were encountered. The infections usually occurred in the
      patients with hepatic cirrhosis (54%) or malignancy (21%) and were community
      acquired (74%). Cases of community-acquired bacteraemia were more likely to have
      cirrhosis, a high severity score at onset, and a worse prognosis than those of
      nosocomial bacteraemia did and nosocomial isolates were less susceptible to
      cefoxitin and cefotaxime. Forty-three percent of cases had a concomitant
      infection focus, such as primary peritonitis, invasive cellulitis or necrotizing
      fasciitis, biliary tract or burn wound infections. Crude fatality rate within 2
      weeks after the onset was 30%. Secondary bacteraemia and a higher severity score
      ( > or = 4) for illness at the first presentation were independently associated
      with a fatal outcome. The therapeutic superiority of beta-lactam and
      aminoglycoside in combination cannot be demonstrated in patients with Aeromonas
      bacteraemia. Cefotaxime resistance emerged in 3.4% of 58 patients treated with a
      cephalosporin for at least 72 h. None of the community-acquired isolates, but one
      quarter of the nosocomial isolates, were resistant to cefotaxime. CONCLUSIONS:
      Aeromonas bacteraemia usually occurred in patients with liver cirrhosis or
      malignancy, and heralded a poor prognosis, especially while associated with a
      relevant infectious source or with a higher severity score at presentation. The
      superiority of aminoglycoside and beta-lactam in combination cannot be
      demonstrated while treating those patients, and the emergence of antimicrobial
      resistance to cephalosporin was a rare event during cephalosporin therapy. Thus,
      a broad-spectrum cephalosporin remains one of the antimicrobial alternatives for
      invasive community-acquired Aeromonas infections.

PMID- 10908023
TI  - SPECT thallium-201 combined with Toxoplasma serology for the presumptive
      diagnosis of focal central nervous system mass lesions in patients with AIDS.
AB  - OBJECTIVE: To determine the utility of brain thallium-201 single photon emission
      computerized tomography (Tl-201 SPECT) combined with Toxoplasma serology for the
      diagnosis of focal CNS lesions in patients with AIDS. METHODS: Sixty-one
      consecutive HIV-infected patients with focal CNS lesion(s) on head computed
      tomography (CT) or MRI scan who underwent brain Tl-201 SPECT and serum Toxoplasma
      serology were evaluated, retrospectively. Thallium-201 uptake ratios were
      calculated by comparing lesion activity to contralateral scalp activity.
      Diagnoses were made by a combination of histology, serology, PCR, and empirical
      response to therapy. Toxoplasma serologies (IgG IFA) were compared in the
      patients with central nervous system (CNS) toxoplasmosis and those without CNS
      toxoplasmosis. RESULTS: Fifty-six patients were evaluable and a definitive
      diagnosis was made in 38 patients: toxoplasmosis (17), lymphoma (14), PML
      (three), Aspergillus (one), tuberculoma (one), Cryptococcus (one), varicella
      zoster virus (one). Patients with lymphoma had significantly higher
      lesion/contralateral scalp ratios compared to patients without lymphoma: 1.03 vs.
      0.67, P < 0.05. Using a cut-off of 0.90 for the lesion/scalp uptake ratios (based
      on analysis of ROC curves) the sensitivity and specificity for the diagnosis of
      lymphoma were 86% and 83%, respectively. Serum Toxoplasma IgG titres were
      significantly higher in patients diagnosed with toxoplasmosis compared to those
      with a diagnosis other than toxoplasmosis, 1:5444 vs. 1:15, P < 0.05. Only one
      patient with confirmed toxoplasmosis had a Toxoplasma serology < 1:256, while no
      patients without toxoplasmosis (including all lymphoma patients) had serologies >
      1:256. CONCLUSIONS: In a series of HIV-infected patients, Tl-201 SPECT was able
      to accurately differentiate primary brain lymphoma from other causes of focal CNS
      lesions in most patients; however, both false positive and false negative results
      occurred. By combining Tl-201 SPECT with serum Toxoplasma IgG, diagnostic
      accuracy was improved.

PMID- 10908024
TI  - Impact of highly active antiretroviral therapy in HIV-positive patients with
      cardiac involvement.
AB  - OBJECTIVES: Cardiac involvement is frequently observed in HIV-infected patients,
      especially in those in the late stage of the disease. This study was designed to
      evaluate the impact of highly active antiretroviral therapy (HAART) in patients
      with cardiac involvement. METHODS: A retrospective study of 1042 patients
      admitted to a Division of Infectious Diseases between 1989 and 1998. During the
      period 1989-1995, 544 patients were treated with nucleoside reverse transcriptase
      inhibitors (NRTI), whereas 498 patients were treated with HAART during the period
      1996-1998. RESULTS: Cardiac involvement, including arrhythmias, pericarditis,
      ischaemia, dilated cardiomyopathy, endocarditis, pulmonary hypertension, and
      myocarditis were observed in 282 of 544 (51.8%) patients treated with NRTI,
      compared with 93 of 498 (18.6%) patients with HAART (P < 0.0001). CONCLUSIONS:
      HAART has significantly decreased the incidence of cardiac involvement,
      especially pericarditis, arrhythmias, and dilated cardiomyopathy.

PMID- 10908025
TI  - Necrotizing proctitis caused by Streptococcus pyogenes.
AB  - We report the case of a 65-year-old patient with peritonitis, septicaemia and
      toxic shock syndrome in whom the primary focus of infection was acute purulent
      proctitis with necrosis. Streptococcus pyogenes serotype T28R28 was isolated from
      blood culture and peritoneal pus. The patient recovered after a prolonged period
      of intensive therapy and four abdominal operations including anterior resection
      of the rectum. We believe this to be the first clinical description of
      streptococcal necrotizing proctitis.

PMID- 10908026
TI  - Infective endocarditis and septic embolization with Ochrobactrum anthropi: case
      report and review of literature.
AB  - Ochrobactrum anthropi, previously known as CDC group Vd, is an aerobic, Gram
      negative bacillus of low virulence that occasionally causes human infection. We
      describe a case of infective endocarditis with O. anthropi complicated by septic
      embolization. A review of all the literature reported cases of O. anthropi
      infection is presented and categorized into 'Central line related', 'Transplant
      related' and "Other pyogenic infections". Mortality appears to be related to the
      underlying disease state, rather than the organism.

PMID- 10908027
TI  - An unusual polymicrobial liver abscess.

PMID- 10908028
TI  - Autoimmune haemolytic anaemia revealing miliary tuberculosis.

PMID- 10908029
TI  - Hyperbaric oxygen can be effective in treating postpartum necrotizing fasciitis
      type I.

PMID- 10908030
TI  - Brain abscess caused by Clostridium sp. secondary to acute otomastoiditis.

PMID- 10908031
TI  - Gas-forming retroperitoneal abscess associated with crepitant myositis of right
      buttock and thigh.

PMID- 10908032
TI  - Fatal Coxsackie A9 virus infection during an outbreak in a neonatal unit.

PMID- 10908033
TI  - Bordetella hinzii, a "new" opportunistic pathogen to think about.

PMID- 10908034
TI  - Ochrobactrum anthropi peritonitis in a CAPD patient.

PMID- 10908035
TI  - Multiple molecular penumbras after focal cerebral ischemia.
AB  - Though the ischemic penumbra has been classically described on the basis of blood
      flow and physiologic parameters, a variety of ischemic penumbras can be described
      in molecular terms. Apoptosis-related genes induced after focal ischemia may
      contribute to cell death in the core and the selective cell death adjacent to an
      infarct. The HSP70 heat shock protein is induced in glia at the edges of an
      infarct and in neurons often at some distance from the infarct. HSP70 proteins
      are induced in cells in response to denatured proteins that occur as a result of
      temporary energy failure. Hypoxia-inducible factor (HIF) is also induced after
      focal ischemia in regions that can extend beyond the HSP70 induction. The region
      of HIF induction is proposed to represent the areas of decreased cerebral blood
      flow and decreased oxygen delivery. Immediate early genes are induced in cortex,
      hippocampus, thalamus, and other brain regions. These distant changes in gene
      expression occur because of ischemia-induced spreading depression or
      depolarization and could contribute to plastic changes in brain after stroke.

PMID- 10908036
TI  - Suppression of endogenous bcl-2 expression by antisense treatment exacerbates
      ischemic neuronal death.
AB  - Previous studies have shown that overexpression of bcl-2 in transgenic mice or by
      viral vectors protects the brain against cerebral ischemia. However, it is not
      known whether bcl-2, which is endogenously expressed in response to ischemia,
      exerts a protective effect. To address this question, the authors blocked the
      endogenous expression of bcl-2 after ischemia using antisense
      oligodeoxynucleotides (ODN). Antisense, sense, scrambled ODN, or vehicles were
      infused in the lateral ventricle of the rat for 24 hours after 30 minutes of
      temporary middle cerebral artery occlusion. Twenty-four hours later the brains
      were removed and bcl-2 protein expression was assayed by Western blot. Antisense
      ODN, but not sense or scrambled ODN treatment, significantly inhibited bcl-2
      protein expression after ischemia. Bcl-2 protein expression was also studied 24
      hours after 60 minutes of temporary middle cerebral artery occlusion in vehicle
      and antisense ODN-treated rats. After 60 minutes of ischemia and vehicle
      treatment, bcl-2 was expressed in many neurons in the ventral cortical mantle and
      the medial striatum. After antisense ODN treatment there were few neurons in this
      region expressing bcl-2, instead most neurons TUNEL labeled. Treatment with the
      antisense ODN, but not sense ODN, increased infarction volume as determined by
      cresyl violet staining 72 hours after ischemia compared with vehicle controls.
      These results suggested that endogenously expressed bcl-2 promoted survival in
      ischemic neurons and was not simply an epiphenomenon in neurons already destined
      to live or die.

PMID- 10908037
TI  - High susceptibility to cerebral ischemia in GFAP-null mice.
AB  - Astrocytes perform a variety of functions in the adult central nervous system
      (CNS) that contribute to the survival of neurons. Thus, it is likely that the
      activities of astrocytes affect the extent of brain damage after ischemic stroke.
      The authors tested this hypothesis by using a mouse ischemia model to compare the
      infarct volume produced in wild-type mice with that produced in mice lacking
      glial fibrillary acidic protein (GFAP), an astrocyte specific intermediate
      filament component. Astrocytes lacking GFAP have been shown to have defects in
      process formation, induction of the blood-brain barrier. and volume regulation;
      therefore, they might be compromised in their ability to protect the CNS after
      injury. The authors reported here that 48 hours after combined permanent middle
      cerebral artery occlusion (MCAO) and 15 minutes transient carotid artery
      occlusion (CAO) GFAP-null mice had a significantly (P < 0.001) larger cortical
      infarct volume (16.7 +/- 2.2 mm3) than their wild-type littermates (10.1 +/- 3.9
      mm3). Laser-Doppler flowmetry revealed that the GFAP-null mice had a more
      extensive and profound decrease in cortical cerebral blood flow within 2 minutes
      after MCAO with CAO. These results indicated a high susceptibility to cerebral
      ischemia in GFAP-null mice and suggested an important role for astrocytes and
      GFAP in the progress of ischemic brain damage after focal cerebral ischemia with
      partial reperfusion.

PMID- 10908038
TI  - Parallel gene expression monitoring using oligonucleotide probe arrays of
      multiple transcripts with an animal model of focal ischemia.
AB  - High density oligonucleotide arrays offer tremendous potential to study gene
      changes occurring in disease states. The authors described the first case of
      using a custom designed high density oligonucleotide probe array containing 750
      genes to monitor the changes in mRNA transcript levels occurring after focal
      ischemia for a period of 3 hours. Permanent middle cerebral artery occlusion in
      the rat resulted in neuronal degeneration in the dorsolateral cortex and striatum
      over a time course of 24 hours. Comparing the changes in hybridization levels in
      the frontal and parietal cortices and the striatum, between the ipsilateral and
      contralateral sides of the brain using the probe arrays resulted in the up
      regulation of 24 genes, which showed greater than a twofold change. Very few
      genes were found to be downregulated after the ischemic insult. Many of the
      immediate early genes (IEGs) such as c-fos, NGFI-A, NGFI-C, and Krox-20 were
      found to be robustly upregulated in the three different regions studied. Other
      genes that were up-regulated in perifocal regions included Arc, Inhibin-beta-A,
      and the phosphatases MKP-1 and MKP-3. The hybridization signal intensity from the
      probe arrays enabled quantification of many genes relative to one another, and
      robust changes in expression were obtained with very little interanimal
      variability. Furthermore, the authors were able to validate the increased
      expression of NGFI-C and Arc using in situ hybridization. This represented the
      first example of using high density oligonucleotide probe arrays in studying the
      expression of many genes in parallel and in discrete brain regions after focal
      ischemia.

PMID- 10908040
TI  - Heme oxygenase-1 and ferritin are increased in cerebral arteries after
      subarachnoid hemorrhage in monkeys.
AB  - Hemoglobin is a key factor in the production of cerebral vasospasm. Metabolism of
      hemoglobin involves breakdown of heme by heme oxygenase (HO) and sequestration of
      the released iron in ferritin. We determined whether subarachnoid hemorrhage
      induces these proteins in cerebral arteries and, if so, in which cells they are
      produced. Whether the changes correlated with vasospasm also was investigated.
      Subarachnoid hemorrhage was created in monkeys, and vasospasm was assessed by
      angiography in cohorts of animals killed 3, 7, or 14 days after the hemorrhage.
      Ferritin and HO-1 messenger ribonucleic acid (mRNA) and protein were measured by
      competitive reverse transcription-polymerase chain reaction and Western blotting
      in hemorrhage-side and control-side cerebral arteries and brain tissue. The
      location of these proteins was determined by immunohistochemistry. There was
      significant vasospasm 3 and 7 days but not 14 days after subarachnoid hemorrhage.
      There were no significant changes in mRNA for HO-1 or ferritin in cerebral
      arteries or brain tissue at any time. There was a significant increase in HO-1
      and ferritin protein in hemorrhage-side compared with control-side cerebral
      arteries at 3, 7, and 14 days. The increase in HO-1 protein was maximal at 3
      days, whereas the increase in ferritin protein was maximal at 7 days. There was
      no detectable increase in HO-1 or ferritin protein in brain tissue at any time.
      Immunohistochemistry localized HO-1 protein and ferritin to cells in the
      adventitia of the arterial wall. We show that subarachnoid hemorrhage is
      associated with a significant increase in HO-1 and ferritin proteins in cerebral
      arteries that begins at least as early as 3 days after the hemorrhage and that
      persists for up to 14 days.

PMID- 10908039
TI  - Differential expression of HSC73 and HSP72 mRNA and proteins between young and
      adult gerbils after transient cerebral ischemia: relation to neuronal
      vulnerability.
AB  - This study presents a quantitative comparison of the time courses and regional
      distribution of both constitutive HSC73 and inducible HSP72 mRNA expression and
      their respective encoded proteins between young (3-week-old) and adult (3-month
      old) gerbil hippocampus after transient global ischemia. The constitutive
      expression of HSC73 mRNA and protein in the hippocampus of the young sham
      operated gerbils was significantly higher than in the adults. The HSC73 mRNA
      expression after ischemia in the CA1 layer of young gerbils was greater than in
      adult gerbils. HSC73 immunoreactivity was not significantly changed after
      ischemia-reperfusion in adult hippocampus, whereas it decreased in young gerbils.
      Ischemia-reperfusion led to induction of HSP72 mRNA expression throughout the
      hippocampus of both young and adult gerbils. HSP72 mRNA induction was more
      intense and sustained in the CA1 subfield of young gerbils; this was associated
      with a marked induction of HSP72 proteins and neuronal survival. The transient
      expression of HSP72 mRNA in the CA1 layer of adult gerbils was not associated
      with a subsequent synthesis of HSP72 protein but was linked to neuronal loss.
      Expression of HSP72 mRNA was shifted to an earlier period of reflow in CA3 and
      dentate gyrus (DG) subfields of young animals. These findings suggest that the
      induction of both HSP72 mRNA and proteins in the CA1 pyramidal neurons of young
      gerbils, as well as the higher constitutive expression of HSC73, may partially
      contribute to higher neuronal resistance of young animals to transient cerebral
      ischemia.

PMID- 10908041
TI  - Neuroprotective agent chlomethiazole attenuates c-fos, c-jun, and AP-1 activation
      through inhibition of p38 MAP kinase.
AB  - Recent evidence suggests that stress-activated protein kinases expressed in glial
      cells have very important roles during cerebral ischemia. The neuroprotective
      agent chlomethiazole, which is known to enhance the conductance at the GABA(A)
      receptor complex, is presently in clinical trials for the treatment of severe
      stroke. Here the authors suggested that chlormethiazole has anti-inflammatory
      properties because it potently and selectively inhibited p38 mitogen-activated
      protein (MAP) kinase in primary cortical glial cultures. The inhibition of p38
      MAP kinase resulted in the attenuation of the induction of c-fos and c-jun mRNA
      and AP-1 DNA binding by lipopolysaccharide (LPS). In addition, chlomethiazole
      inhibited the activation of an AP-1-dependent luciferase reporter plasmid in SK-N
      MC human neuroblastoma cells in response to glutamate. Chlomethiazole inhibited
      the p38 MAP kinase activity as revealed by the decrease in the LPS-induced
      phosphorylation of the substrates ATF-2 and hsp27, whereas the phosphorylation
      status of the p38 MAP kinase itself was unaffected. Interestingly, chlomethiazole
      exhibited an IC(50) of approximately 2 micromol/L for inhibition of c-fos mRNA
      expression, indicating 25 to 75 times higher potency than reported EC(50) values
      for enhancing GABA(A) chloride currents. The results indicated a novel mechanism
      of action of chlomethiazole, and provided support for a distinctive role of p38
      MAP kinase in cerebral ischemia.

PMID- 10908042
TI  - Alteration of MAP kinase pathways after transient forebrain ischemia.
AB  - Extracellular regulated kinase (ERK) transduce growth factor signals while c-Jun
      NH(2)-terminal kinase (JNK) delivers stress signals into the nuclei for
      regulation of gene expression. These signaling pathways were studied by laser
      scanning confocal microcopy and Western blot analysis using phospho-specific
      antibodies on rat brains that were subjected to 15 minutes transient forebrain
      ischemia followed by varied periods of reperfusion. Extracellular regulated
      kinase was activated at 30 minutes and 4 hours of reperfusion in the nuclei and
      dendrites of surviving dentate gyrus (DG) cells, but not in dying CA1 neurons
      after ischemia. Tyrosine phosphorylation of Trk kinase, an ERK upstream growth
      factor receptor, was elevated in the DG tissue, and to a lesser extent in the CA1
      region. In addition, phosphorylation of activating transcription factor-2 (ATF-2)
      and c-Jun was selectively increased in CA1 dying neurons during the late period
      of reperfusion. These findings suggested that the Trk-ERK signaling pathway might
      be neuroprotective for dentate granule cells. The activation of ATF-2 and c-Jun
      pathways in the late period of reperfusion in CA1 dying neurons might reflect
      damage signals in these neurons. These results suggested that the lack of
      protective signals acting in concert with the presence of damage signals in CA1
      neurons after ischemia might contribute to delayed neuronal death after transient
      forebrain ischemia.

PMID- 10908043
TI  - Selective Lutheran glycoprotein gene expression at the blood-brain barrier in
      normal brain and in human brain tumors.
AB  - The Lutheran (LU) glycoprotein was shown to be a specific marker of brain
      capillary endothelium, which forms the blood-brain barrier (BBB) in vivo. A 1.5
      kb partial cDNA encoding the bovine LU was isolated from a bovine brain capillary
      cDNA library. Sequence analysis showed that the bovine and human LU had a 75% and
      79% identity in the amino acid and nucleotide sequences, respectively. Northern
      blot analysis demonstrated a very high level of gene expression of the LU
      transcript in freshly isolated bovine brain capillaries, but no measurable LU
      mRNA in whole bovine brain. The high level of LU gene expression was maintained
      when bovine brain capillary endothelium was grown in tissue culture. Because many
      BBB specific genes are downregulated in tissue culture and in brain tumors, the
      expression of the LU mRNA and immunoactive LU protein was investigated in primary
      and metastatic human brain tumors. Immunocytochemistry of fresh frozen human
      brain and human brain tumors showed abundant immunostaining of brain capillary
      endothelium. Northern blot analysis showed the presence of LU transcripts in a
      panel of primary and metastatic human brain tumors. These studies demonstrated
      that the LU glycoprotein was a novel new marker of the BBB, and unlike other BBB
      specific genes, there was a persistent gene expression of the LU glycoprotein
      both in brain capillary endothelial cells grown in culture and in the endothelium
      of capillaries perfusing human brain cancer.

PMID- 10908044
TI  - Saccadic suppression induces focal hypooxygenation in the occipital cortex.
AB  - This study investigated how a decrease in neuronal activity affects cerebral
      blood oxygenation employing a paradigm of acoustically triggered saccades in
      complete darkness. Known from behavioral evidence as saccadic suppression,
      electrophysiologically it has been shown in monkeys that during saccades an
      attenuation of activity occurs in visual cortex neurons (Duffy and Burchfiel,
      1975). In study A, using blood oxygen level-dependent (BOLD) contrast functional
      magnetic resonance imaging (fMRI), the authors observed signal intensity
      decreases bilaterally at the occipital pole during the performance of saccades at
      2 Hz. In study B.1, the authors directly measured changes in deoxyhemoglobin
      [deoxy-Hb] and oxyhemoglobin [oxy-Hb] concentration in the occipital cortex with
      near-infrared spectroscopy (NIRS). Whereas a rise in [deoxy-Hb] during the
      performance of saccades occurred, there was a drop in [oxy-Hb]. In a second NIRS
      study (B.2), subjects performed saccades at different rates (1.6, 2.0, and 2.3
      Hz). Here the authors found the increase in deoxy-Hb and the decrease of oxy-Hb
      to be dependent on the frequency of the saccades. In summary, the authors
      observed a focal hypooxygenation in the human visual cortex dependent on the
      saccade-frequency in an acoustically triggered saccades paradigm. This could be
      interpreted as evidence that corresponding to the focal hyperoxygenation observed
      in functional brain activation, caused by an excessive increase in cerebral blood
      flow (CBF) over the increase in CMRO2 during decreased neuronal activity CBF, is
      more reduced than oxygen delivery.

PMID- 10908045
TI  - Validation and reproducibility of measurement of 5-HT1A receptor parameters with
      [carbonyl-11C]WAY-100635 in humans: comparison of arterial and reference tisssue
      input functions.
AB  - Serotonin 5-HT(1A) receptors are implicated in the pathophysiology of
      neuropsychiatric conditions. The goal of this study was to evaluate methods to
      derive 5-HT(1A) receptor parameters in the human brain with positron emission
      tomography (PET) and [carbonyl-(11)C]WAY 100635. Five healthy volunteer subjects
      were studied twice. Three methods of analysis were used to derive the binding
      potential (BP), and the specific to nonspecific equilibrium partition coefficient
      (k3/k4). Two methods, kinetic analysis based on a three compartment model and
      graphical analysis, used the arterial plasma time-activity curves as the input
      function to derive BP and k3/k4. A third method, the simplified reference tissue
      model (SRTM), derived the input function from uptake data of a region of
      reference, the cerebellum, and provided only k3/k4. All methods provided
      estimates of regional 5-HT(1A) receptor parameters that were highly correlated.
      Results were consistent with the known distribution of 5-HT(1A) receptors in the
      human brain. Compared with kinetic BP, graphical analysis slightly underestimated
      BP, and this phenomenon was mostly apparent in small size-high noise regions.
      Compared with kinetic k3/k4, the reference tissue method underestimated k3/k4 and
      the underestimation was apparent primarily in regions with high receptor density.
      Derivation of BP by both kinetic and graphical analysis was highly reliable, with
      an intraclass correlation coefficient (ICC) of 0.84 +/- 0.14 (mean +/- SD of 15
      regions) and 0.84 +/- 0.19, respectively. In contrast, the reliability of k3/k4
      was lower, with ICC of 0.53 +/- 0.28, 0.47 +/- 0.28, and 0.55 +/- 0.29 for
      kinetic, graphical, and reference tissue methods, respectively. In conclusion,
      derivation of BP by kinetic analysis using the arterial plasma input function
      appeared as the method of choice because of its higher test-retest
      reproducibility, lower vulnerability to experimental noise, and absence of bias.

PMID- 10908047
TI  - ADSA Foundation Scholar award. Dairying and the environment.
AB  - Increases in average herd size have resulted in increased concentrations of
      manure at dairies. Inadequate or insufficient manure management practices and
      greater focus on agricultural pollution from environmental groups have increased
      the need for scrutiny from regulatory agencies. An overview of the sequence of
      activities that led to the development and final approval of the National Animal
      Feeding Operation Strategy is presented. The Strategy and associated policy
      changes serve as the foundation for new enforcement and compliance goals and
      probable alterations to existing permit requirements. Lastly, identified research
      needs and educational opportunities are presented.

PMID- 10908046
TI  - Striatal kinetic modeling of FDOPA with a cerebellar-derived constraint on the
      distribution of volume of 30MFD: a PET investigation using non-human primates.
AB  - The peripherally born metabolite of FDOPA, 3-O-Methyl-FDOPA (3OMFD), crosses the
      blood-brain barrier, thus complicating positron emission tomography-FDOPA (PET
      FDOPA) data analysis. In previous reports the distribution volume (DV) of 3OMFD
      was constrained to unity. We have recently shown that the forward transport rate
      constant of FDOPA (K(S1)) and the cerebellum-to-plasma ratio (C(b)/C(p)), a
      measure for the DV of 3OMFD, are functions of plasma large neutral amino acid
      (LNAA) concentration. Given large interstudy and intersubject differences in
      plasma LNAA levels, variations in the DV of 3OMFD are significant. In this
      report, the authors propose a constraint on the DV of 3OMFD that accounts for
      these variations. Dynamic PET-FDOPA scans were performed on 12 squirrel monkeys
      and 12 vervet monkeys. Two sets of constraints were employed on the compartmental
      model--M1 or M2. In M1, the striatal DV of 3OMFD was constrained to unity; in M2,
      the striatal DV of 3OMFD was constrained to an estimate derived from the
      cerebellum. Striatal and cerebellar time-activity curves were fitted using FDOPA
      and 3OMFD plasma input functions. The estimate of K(S1) and that of the
      compartmental FDOPA uptake-constant (K(i)), both obtained using M2, were adjusted
      to values corresponding to average LNAA levels. Finally, K(i) was compared with
      the graphical uptake-constant (PK(j)). With the use of constraint M2,
      intersubject variability of squirrel monkey k(S3) and K(i) was reduced by 45% and
      53%, respectively; and for vervet monkeys, by 54% and 44%, respectively.
      Intersubject variability of K(1) and K(i) was further reduced after correction
      for variations in intersubject plasma LNAA levels (for squirrel monkeys, by 67%
      and 41%; for vervet monkeys, by 40% and 36%, respectively). K(i) correlation to
      PK(i) was enhanced to identity. Finally, average cerebellar k(C2) estimates were
      more than 2.5-fold higher than striatal k(S2) estimates (P < 0.0001). In modeling
      of PET-FDOPA data, it cannot be assumed that the DV of 3OMFD is unity. The
      cerebellar-derived constraint furnishes a reliable estimate for the DV of 3OMFD.
      Invoking the constraint and correcting for variations in plasma LNAA
      significantly reduced interstudy and intersubject variations in parameter
      estimates.

PMID- 10908048
TI  - Effects of duodenal infusions of palmitic, stearic, or oleic acids on milk
      composition and physical properties of butter.
AB  - Four dairy cows fitted with a duodenal cannula were used in a 4 x 4 Latin square
      design to investigate the effects of daily duodenal infusion of 500 g of fatty
      acids (containing mainly C16:0, C18:0, or cis-C18:1) on fecal concentrations of
      fatty acids, fatty acid profiles of milk fat, and solid fat content of butter.
      Fecal concentrations of C16:0 and especially of C18:0 were increased by duodenal
      infusion. Infusion with C16:0 increased the proportion of C16:0 in milk fat and
      delayed softening of butter when the temperature rose. Infusion with C18:0
      resulted only in a slight increase of C18:0 proportion in milk fat and did not
      significantly affect solid fat in butter between -10 and 30 degrees C. With the
      infusion of cis-C18:1, the proportion of cis-C18:1 in milk fat was more than
      twice that of control, to the detriment of C16:0. Butter contained low proportion
      of solid fat, even at low temperatures. Increasing C16:0 or cis-C18:1 in milk
      fatty acid via duodenal infusion can be used to study their specific effects on
      butter characteristics, but, because of a low transfer from infusion to milk,
      this method is less efficient with C18:0.

PMID- 10908049
TI  - Isolation and structural analysis of antihypertensive peptides that exist
      naturally in Gouda cheese.
AB  - Seven kinds of ripened cheeses (8-mo-aged and 24-mo-aged Gouda, Emmental, Blue,
      Camembert, Edam, and Havarti) were homogenized with distilled water, and water
      soluble peptides were prepared by C-18 hydrophobic chromatography. The inhibitory
      activity to angiotensin I-converting enzyme and decrease in the systolic blood
      pressure in spontaneously hypertensive rats were measured before and after oral
      administration of each peptide sample. The strongest depressive effect in the
      systolic blood pressure (-24.7 mm Hg) and intensive inhibitory activity to
      angiotensin I-converting enzyme (75.7%) were detected in the peptides from 8-mo
      aged Gouda cheese. Four peptides were isolated by HPLC with reverse-phase and gel
      filtration modes. Their chemical structures and origins, clarified by combination
      analyses of protein sequencing, amino acid composition, and mass spectrometry,
      were as follows: peptide A, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln [alpha(s1)-casein
      (CN), B-8P; f 1-9]; peptide B, Arg-Pro-Lys-His-Pro-Ile-Lys-His-Gln-Gly-Leu-Pro
      Gln (alpha(s1)-CN, B-8P; f 1-13); peptide F, Tyr-Pro-Phe-Pro-Gly-Pro-Ile-Pro-Asn
      (beta-CN, A2-5P; f 60-68); and peptide G, Met-Pro-Phe-Pro-Lys-Tyr-Pro-Val-Gln-Pro
      Phe (beta-CN, A2-5P; f 109-119). Peptides A and F, which were chemically
      synthesized, showed potent angiotensin I-converting enzyme inhibitory activity
      with little antihypertensive effects.

PMID- 10908050
TI  - Proteolysis in Manchego-type cheese salted by brine vacuum impregnation.
AB  - A new salting procedure based on the brine vacuum impregnation of porous products
      was tested on Manchego-type cheese and compared with conventional brine
      immersion. Its effect on cheese proteolysis throughout a 90-d ripening period was
      determined. Three cheese regions were evaluated (the rind, the middle, and the
      internal regions). The parameters analyzed were total N, water-soluble N, soluble
      N in trichloroacetic acid and soluble N in phosphotungstic acid by using the
      Kjeldahl method, casein profile by urea-PAGE, and peptide profile of the water
      soluble nitrogen extract by reverse-phase HPLC. Free amino acid formation was
      monitored with a spectrophotometric method by using a Cd-ninhydrin reagent.
      Globally, proteolysis was significantly affected by ripening stage (increasing
      throughout all the maturation period studied) and cheese region (rind showed a
      proteolysis pattern different from the middle and internal regions). The salting
      procedure only affected cheese proteolysis in the rind, whereas conventional
      brine-salted cheeses showed lower proteolysis than vacuum-impregnated cheeses.

PMID- 10908051
TI  - Short communication: salt extends the upper temperature limit for growth of
      Lactococcus lactis ssp. cremoris on solid M17 medium.
AB  - We have determined conditions for plating of the Lactococcus lactis ssp. cremoris
      laboratory strain MG1363 on solid M17 broth at 38 degrees C, which is required
      for the optimal use of the pGhost plasmids. The addition of 1% NaCl (or KCl,
      potassium acetate, or sucrose at 170 mM) to M17 agar plates results in extension
      of the upper temperature limit for growth from 37 to 40 degrees C; no decrease in
      plating efficiency was detected from 30 to 39 degrees C.

PMID- 10908052
TI  - Reproductive performance of Holstein cows receiving somatotropin.
AB  - Some dairy producers resist using bovine somatotropin (bST) beginning at 9 wk
      postpartum because of the concern that fertility is compromised. We conducted a
      trial with a total of 205 Holstein cows, 100 multiparous and 105 primiparous, to
      evaluate reproductive performance in two high producing herds in Arizona and
      southern California. Rolling herd averages for both herds for milk production
      exceeded 10,700 kg/yr. Data were collected for cows calving December 1996 through
      August 1997. The voluntary waiting period was 60 d postcalving, with cows
      randomly assigned to receive bST or no treatment (controls). In the 180-d
      interval after calving, 65.4% (68/104) of the control cows were diagnosed
      pregnant. With bST-treated cows, 48.5% (49/101) were pregnant in that same
      interval. A chi-square value from a linear model indicated that pregnancy outcome
      differed significantly between treatment groups. With a similar method of
      analysis, first-service conception rate was not significantly different between
      treatment groups. An extended voluntary wait and breeding interval is recommended
      for cows receiving bST, similar to suggestions from other published reports.

PMID- 10908053
TI  - Tail-docking influences on behavioral, immunological, and endocrine responses in
      dairy heifers.
AB  - Behavioral and physiological changes were measured following tail-docking in
      primiparous heifers. One month before projected first parturition, 21 heifers
      were assigned to control (nondocked), docked, or docked with lidocaine groups.
      Heifers were banded to initiate tail-docking and the necrotic tail was removed
      after 144 h. Physiological, immunological, and behavioral measures were taken for
      240 h following banding. Cortisol was not different for control and treated
      heifers. Haptoglobin increased for docked heifers by 168 h postbanding (24 h
      postdocking). Alpha1-acid glycoprotein decreased as haptoglobin increased, and
      alpha1-acid glycoprotein increased until 240 h postbanding. Tumor necrosis factor
      alpha increased only with lidocaine and did not show an effect of docking by 240
      h postbanding. Lymphocyte phenotyping demonstrated increased CD4+ and CD8+
      peripheral blood mononuclear cells for docked plus lidocaine heifers and
      gammadelta+ cells of those heifers tended to be reduced compared with docked
      heifers. Eating was the only maintenance behavior affected by banding in both
      docked groups (increased with banding and decreased with docking). The initial
      banding procedure did not alter heifer physiology and altered only eating
      behavior, but the cutting of the tail (docking) increased haptoglobin in response
      to the tissue damage and returned eating behavior to baseline. The use of
      lidocaine to anesthetize the tail before banding affected lymphocyte phenotypes
      and TNF-alpha (banding alone did not alter these parameters).

PMID- 10908054
TI  - Effect of dietary IgG source (colostrum, serum, or milk-derived supplement) on
      the efficiency of Ig absorption in newborn Holstein calves.
AB  - This study was designed to compare the absorptive efficiency of IgG from a
      commercial bovine serum product (bovine serum), cow colostrum (positive control),
      and two commercial milk-derived IgG supplements (supplement 1 and supplement 2).
      Newborn Holstein calves, collected at birth and prior to the consumption of
      colostrum, were allotted to treatment by alternating birth order. Colostrum
      supplement treatments were fed according to manufacturer's recommendations at
      birth and again at 12 h. This strategy resulted in varying masses of total IgG
      being offered to the calves (200, 90, 50, and 60 g of IgG for colostrum, bovine
      serum, supplement 1, and supplement 2, respectively). Blood samples were
      collected at 0, 12, and 24 h after the end of treatment administration. Plasma
      volume was estimated as 9.10% of birth weight. Apparent efficiency of IgG
      absorption at 24 h was determined. Plasma IgG concentrations at 24 h differed for
      each treatment (12.1, 6.8, 2.2, and 3.5 g of IgG/L for colostrum, bovine serum,
      supplement 1, and supplement 2, respectively). Apparent efficiency of IgG
      absorption was greatest for bovine serum compared with colostrum and supplement
      1. No treatment differences were detected on the occurrence of mortality.
      However, calves fed bovine serum tended to have fewer treatments for illness
      compared with calves fed colostrum and supplement 1. Calves receiving bovine
      serum-derived IgG had improved IgG absorption efficiency and a tendency toward
      fewer medical treatments compared with calves consuming colostrum or a dried
      colostrum product.

PMID- 10908055
TI  - Effects of daily gain in pre- and postpubertal replacement dairy heifers on body
      condition score, body size, metabolic profile, and future milk production.
AB  - Two trials were conducted to evaluate the effect of moderate (0.7 kg) and
      accelerated (0.9 kg) average daily gain before (trial 1) and after (trial 2)
      puberty on body condition, metabolic profile, and first lactation milk production
      of Italian Holstein-Friesian heifers. There were 20 heifers in trial 1 and 22 in
      trial 2. Trials started when heifers averaged 150 and 300 kg of body weight in
      trial 1 and 2, respectively, and lasted 7 mo (experimental period). Across diet
      groups, half of the heifers were mated at first estrus after 370 kg and the other
      half after 420 kg of body weight gain. Actual average daily gains were 0.667 and
      0.775 kg in trial 1 and 0.748 and 0.824 kg in trial 2 for moderate and
      accelerated experimental groups, respectively. Diets for high average daily gain
      did not affect body condition during growing phase in trial 1, whereas it did in
      trial 2. High average daily gain increased plasma glucose in trial 1 and plasma
      urea concentration in trial 2. Rearing diet did not affect milk production and
      milk protein percent; age in both trials. High average daily gain decreased milk
      fat percentage in trial 2. Early calving negatively influenced milk production in
      both trials and milk fat percentage in trial 1. Early calving heifers showed
      higher protein percentage than those with late calving only in trial 1.

PMID- 10908056
TI  - Microbial populations, fermentation end-products, and aerobic stability of corn
      silage treated with ammonia or a propionic acid-based preservative.
AB  - We studied the effects of ammonia treatment on microbial populations during the
      fermentation of corn silage. We also compared the effects of ammonia to a
      preservative containing buffered propionic acid and other antifungal compounds on
      the fermentation and aerobic stability of corn silage. In the first experiment,
      whole-plant corn was ensiled without treatment or treated with ammonia-N to
      supply an additional 0.3% N (fresh-forage basis). The addition of ammonia
      immediately increased silage pH and had no effect on numbers of lactic acid
      bacteria, but delayed their growth compared with untreated silage. Numbers of
      enterobacteria declined more slowly, but numbers of yeasts and molds declined
      more quickly in silage treated with ammonia. During the early stages of ensiling,
      lactic acid increased more rapidly in untreated than in treated silage. The
      reverse was true for acetic acid concentrations. When exposed to air, growth of
      yeasts and molds was delayed in ammonia-treated silage. In a second experiment,
      various levels (0.1 to 0.3%, fresh weight) of ammonium-N or a preservative with
      buffered propionic acid were added to whole-plant corn and allowed to ensile for
      106 d. Silage treated with ammonia had a greater ratio of L- to D-lactic acid
      than did other silages. Untreated silage was aerobically stable for 32.3 h,
      whereas the low (42 h) and moderate (52.7 h) concentrations of both additives
      numerically improved aerobic stability. High concentrations of ammonia-N (0.3%)
      or a buffered propionic acid preservative (0.3%), markedly improved the aerobic
      stability of corn silage (82 and 69 h for ammonia and propionic acid-treated
      silage, respectively).

PMID- 10908058
TI  - Short communication: a novel system to estimate protein degradability in legume
      and grass hays.
AB  - Previous research from our laboratory has demonstrated that near-infrared
      reflectance spectroscopy has utility in predicting rumen-undegradable protein
      (RUP) contents of legume and grass silages. This study was conducted to evaluate
      whether application of previous research techniques could yield a useful near
      infrared reflectance spectroscopy RUP prediction system for legume and grass
      hays. Legume and grass hays (n = 106) were evaluated for RUP content by in situ
      techniques in four ruminally cannulated cows. In situ RUP for legume and grass
      hays averaged 25.9% CP and ranged from 14.6 to 45.5% CP, respectively. We
      developed a near-infrared reflectance spectroscopy RUP calibration equation for
      the legume and grass hay data set using in situ RUP contents as base data. This
      procedure resulted in an acceptable (R2 = 0.87, SE = 2.46% CP) near-infrared
      reflectance spectroscopy equation to predict RUP content of legume and grass
      hays. Data suggest that near-infrared spectroscopy predicts RUP contents of
      legume and grass hays with accuracies similar to legume and grass silages.

PMID- 10908057
TI  - Enzyme, bacterial inoculant, and formic acid effects on silage composition of
      orchardgrass and alfalfa.
AB  - We evaluated the effects of cellulase (from Trichoderma longibrachiatum)
      application rates on neutral detergent fiber (NDF) concentration and fermentation
      products of orchardgrass (Dactylis glomerata L.) and alfalfa (Medicago sativa L.)
      silages harvested with decreasing dry matter (DM) digestibility. Additionally,
      the impacts of inoculant (Lactobacillus plantarum and Pediococcus cerevisiae),
      pectinase (from Aspergillus niger), or formic acid on silage composition were
      studied. Forages wilted to a DM content of about 320 g/kg were ensiled in
      laboratory silos for 60 d. Cellulase, combined with inoculant, was applied at 2,
      10, and 20 ml/kg of herbage (at least 2500 IU/ml). Cellulase at 10 ml/kg was also
      applied alone or in combination with pectinase and inoculant or formic acid. The
      NDF concentration of orchardgrass silage decreased with increasing cellulase up
      to 20 ml/kg, at which NDF content was decreased by 30%. The NDF concentration of
      alfalfa silage decreased with increasing cellulase application up to 10 ml/kg, at
      which NDF content was decreased by 13%. Immature plants were more responsive to
      cellulase treatment than mature plants. Cellulase at 2 ml/kg combined with
      inoculant improved fermentation characteristics of the silages but generally,
      there was no effect on silage fermentation by higher cellulase applications,
      resulting in an accumulation of sugar. The improved fermentation of orchardgrass
      treated with cellulase and inoculant was mostly related to the effect of
      inoculant, whereas cellulase alone improved fermentation characteristics of
      alfalfa silage and this effect was enhanced by addition of inoculant. Decreased
      NDF and increased sugar concentrations did not improve the in vitro DM
      digestibility of cellulase-treated silages.

PMID- 10908059
TI  - Influences of saturation ratio of supplemental dietary fat on digestion and milk
      yield in dairy cows.
AB  - Four multiparous, ruminally and duodenally cannulated Holstein cows in
      midlactation were utilized in a 4 x 4 Latin square to evaluate the effects of
      supplemental fat from sources varying in proportions of unsaturated and saturated
      fatty acids on nutrient digestion and lactation performance. All diets (45%
      alfalfa hay) contained 12% whole cottonseed (as-fed); treatments were no
      supplemental fat (control, 3% total fatty acids, dry matter basis) or additional
      2% tallow, 2% yellow grease, or 2% blend (60% tallow: 40% yellow grease). The
      unsaturated to saturated fatty acid ratios were 1:1 for tallow and 2.5:1 for
      yellow grease. Dry matter intake, apparent ruminal and total tract
      digestibilities of organic matter, neutral detergent fiber, acid detergent fiber,
      N, and fatty acids, and microbial efficiency were similar across treatments.
      Microbial N flow to the duodenum was increased by yellow grease. Supplemental fat
      reduced the postruminal digestibility of fatty acids, primarily the saturated
      fatty acids; increasing saturation of the fat source magnified the reduction.
      Total volatile fatty acid concentrations and ruminal fluid pH were unaffected by
      fat supplementation or saturation level. Blend decreased ruminal pH and acetate
      to propionate ratio. Yields of milk and milk fat increased with fat
      supplementation. Concentrations and yields of trans vaccenic acid in milk
      increased linearly with the unsaturated fatty acid content of the fat supplement.
      Modest supplementation using highly unsaturated fats to diets containing whole
      cottonseed can increase milk production without disturbing rumen function,
      evident by the similar VFA concentrations, nutrient digestibilities, and milk
      composition.

PMID- 10908060
TI  - Milk production and composition, rumen fermentation parameters, and grazing
      behavior of dairy cows supplemented with different forms and amounts of corn
      grain.
AB  - The objectives were to compare milk production and composition, change in body
      weight and body condition score, rumen fermentation parameters and grazing
      patterns by cows when supplemented with different forms and amounts of corn
      grain. In experiment 1, 36 Holstein cows were supplemented with either 6, 6, 6,
      or 4 kg/d of dry matter of high moisture corn, coarsely ground corn, finely
      ground corn, or high moisture corn in two equal daily feedings, respectively.
      Milk yield (30.3 kg/d), milk protein (2.97%), and milk urea N (14.7 mg/dl) were
      not different among treatments. Body weight change and body condition score
      change were similar (23.1 kg and -0.24) for the 10-wk study. During experiment 2,
      four rumen cannulated cows in midlactation were supplemented with 6 kg/d of dry
      matter from either coarsely ground corn or high moisture corn in two equal
      feedings after milking. After the p.m. milking, ruminal pH was measured and rumen
      fluid samples, were collected from cows to determine ammonia N and volatile fatty
      acids at 0.5, 1, 2, 3, ...8 h post-corn feeding during grazing. Ruminal pH values
      were similar for corn supplements, and, with one exception, were 6.0 or below
      between 5 and 8 h. Ruminal ammonia-N concentrations reached a maximum at 7 h
      also. In experiment 3, 40 cows were observed for grazing behavior every 30 min
      for two consecutive days. Cows grazed an average of 6.4 h/d, 4.1 h in the
      afternoon and 2.3 h in the morning. Milk yield, milk composition, change in body
      weight, and body condition were similar regardless of the type or amount of corn
      supplemented.

PMID- 10908061
TI  - A method to analyze production responses in dairy herds.
AB  - Milk production was simulated in a 50-cow herd averaging 8182 kg of 305-d milk
      with a standard deviation of 1364 kg. Herd demographics were 35% first lactation,
      20% second lactation, and 45% third or greater lactation cows. A lactation model
      was developed with the Wood's equation (Milk/d = A*DIM*e(-c*dim)) to which random
      variation was added to be consistent with a coefficient of variation of 10% for
      daily milk production. Five sequential sampling periods, 30 d apart, were
      randomly selected for the experiment. For each of these sampling periods data
      were simulated for cow, lactation number, milk, and days in milk (DIM). To the
      third sampling period, a known input was pulsed into each cow record to simulate
      a change in milk production. Inputs and number of herds simulated were -1.140 kg
      and 15 herds, 0.909 kg and 30 herds, -0.455 kg and 20 herds, 0 kg and 65 herds,
      0.455 kg and 21 herds, -0.909 kg and 47 herds, 1.140 kg and 20 herds, and 2.270
      kg and 15 herds. Regression by cow was used to estimate milk production change
      for the known inputs: Milk(ijk) = Intercept + beta(i)*DIM(ij) + TRT(ik) +
      epsilon(ijk). Parameter estimates for each cow were submitted to analysis of
      variance with herd as a class variable. The least square mean of TRT (dummy
      variable for known input of milk volume change) for herd was tested for
      difference from zero based on a "t" statistic. Herd responses were classed as
      negative, not different from zero, and greater than zero based on P < 0.10. Herd
      responses were categorized based on the known input to assess the ability of the
      method to detect a change in production. The mean estimate of TRT from the
      regression analysis was used to assess the ability of the method to estimate the
      magnitude of the known input. The regression method was able to detect changes in
      production greater than 0.455 kg, but is more useful when changes of 0.9 kg or
      greater are shown. Adjustment for days postcalving on first test day is necessary
      to correct for the bias in linear regression to estimate response across the
      curvilinear milk production function.

PMID- 10908062
TI  - Performance of lactating dairy cows fed alfalfa or red clover silage as the sole
      forage.
AB  - Three Latin square trials, with 20 (two trials) or 24 (one trial) multiparous
      lactating Holstein cows (four in each trial with ruminal cannulae), compared the
      feeding value of red clover and alfalfa silages harvested over 3 yr. Overall, the
      forages contained similar amounts of neutral detergent fiber and acid detergent
      fiber; however, red clover silage contained more hemicellulose, less ash and
      crude protein (CP), and only 67% as much nonprotein N, as a proportion of total
      N, as did alfalfa silage. Diets were formulated with equal dry matter (DM) from
      alfalfa or red clover silage and contained on average 65% forage, 33 or 30%
      ground high moisture ear corn, and 0 or 3% low soluble fishmeal (DM basis). Diets
      fed in the Latin squares contained (mean dietary CP): 1) alfalfa (17.8% CP); 2)
      red clover (15.1% CP); 3) alfalfa plus fishmeal (19.6% CP); and 4) red clover
      plus fishmeal (16.9% CP). Although performance varied somewhat among trials,
      overall statistical analysis showed that replacing alfalfa with red clover
      reduced yields of milk, fat-corrected milk, fat, protein, lactose, and SNF; these
      effects were related to the 1.2 kg/d lower DM intake for cows fed red clover.
      Replacing alfalfa with red clover improved body weight gain and reduced
      concentrations of milk and blood urea and ruminal NH3. Apparent digestibility of
      DM, organic matter, neutral detergent fiber, acid detergent fiber, and
      hemicellulose all were greater when red clover was fed. There were no significant
      forage x fishmeal interactions for DM intake and yield of milk and milk
      components, indicating that supplementation with rumen undegradable protein gave
      similar increases in production on both forages. Net energy of lactation (NE(L)),
      estimated from maintenance, mean milk yield, and body weight change, in alfalfa
      and red clover silage were, respectively, 1.25 and 1.38 Mcal NE(L)/kg of DM,
      indicating 10% greater NE(L) in red clover.

PMID- 10908063
TI  - Digital characteristics in commercial dairy herds fed metal-specific amino acid
      complexes.
AB  - Five commercial dairy herds in Central New York fed metal-specific amino acid
      complexes were selected to evaluate digital characteristics. During the first
      year (period 1), herds were evaluated by a specific procedure by one individual.
      Three herds were not supplemented and two herds were supplemented with zinc
      methionine. During the subsequent year (period 2) all herds were switched to a
      combination of zinc methionine, copper lysine, manganese methionine, and cobalt
      glucoheptonate and evaluated in the same way as during period 1. There was no
      effect of period on incidence of heel erosion and interdigital dermatitis. During
      period 2, there was a reduced incidence of double soling, white line separation,
      sole hemorrhages, sole ulcers, and papillomatous digital dermatitis, and the
      incidence of wall ridges tended to be reduced compared with period 1. There was
      no effect of period on the incidence of abaxial wall lesions, digital arthritis,
      or foot rot, although the overall incidence of these disorders was low. During
      period 2, when cows were fed a combination of complexed trace minerals, there was
      a general reduction in the incidence of digital disorders associated with the
      laminitis syndrome complex compared with period 1; however, other time-related
      differences existed that may confound interpretation.

PMID- 10908064
TI  - Integration of metabolism and intake regulation: a review focusing on
      periparturient animals.
AB  - There has been great interest in dry matter intake regulation in lactating dairy
      cattle to enhance performance and improve animal health and welfare. Predicting
      voluntary dry matter intake (VDMI) is complex and influenced by numerous factors
      relating to the diet, management, housing, environment and the animal. The
      objective of this review is to identify and discuss important metabolic factors
      involved in the regulation of VDMI and their integration with metabolism. We have
      described the adaptations of intake and metabolism and discussed mechanisms of
      intake regulation. Furthermore we have reviewed selected metabolic signals
      involved in intake regulation. A substantial dip in VDMI is initiated in late
      pregnancy and continues into early lactation. This dip has traditionally been
      interpreted as caused by physical constraints, but this role is most likely
      overemphasized. The dip in intake coincides with changes in reproductive status,
      fat mass, and metabolic changes in support of lactation, and we have described
      metabolic signals that may play an equally important role in intake regulation.
      These signals include nutrients, metabolites, reproductive hormones, stress
      hormones, leptin, insulin, gut peptides, cytokines, and neuropeptides such as
      neuropeptide Y, galanin, and corticotrophin-releasing factor. The involvement of
      these signals in the periparturient dip in intake is discussed, and evidence
      supporting the integration of the regulation of intake and metabolism is
      presented. Still, much research is needed to clarify the complex regulation of
      VDMI in lactating dairy cows, particularly in the periparturient animal.

PMID- 10908065
TI  - Effects of diet on short-term regulation of feed intake by lactating dairy
      cattle.
AB  - Physical and chemical characteristics of dietary ingredients and their
      interactions can have a large effect on dry matter intake (DMI) of lactating
      cows. Physical limitations caused by distension of the reticulo-rumen or other
      compartments of the gastrointestinal tract often limit DMI of high producing cows
      or cows fed high forage diets. Fermentation acids also limit DMI from a
      combination of increased osmolality in the reticulo-rumen and specific effects of
      propionate, although the mechanisms are not clear. The specific physical and
      chemical characteristics of diets that can affect DMI include fiber content, ease
      of hydrolysis of starch and fiber, particle size, particle fragility, silage
      fermentation products, concentration and characteristics of fat, and the amount
      and ruminal degradation of protein. Site of starch digestion affects the form of
      metabolic fuel absorbed, which can affect DMI because absorbed propionate appears
      to be more hypophagic than lactate or absorbed glucose. Dry matter intake is
      likely determined by integration of signals in brain satiety centers. Difficulty
      in measurement and extensive interactions among the variables make it challenging
      to account for dietary effects when predicting DMI. However, a greater
      understanding of the mechanisms along with evaluation of animal responses to diet
      changes allows diet adjustments to be made to optimize DMI as well as to optimize
      allocation of diet ingredients to animals. This paper discusses some of the
      characteristics of dietary ingredients that should be considered when formulating
      diets for lactating dairy cows and when allocating feeds to different groups of
      animals on the farm.

PMID- 10908066
TI  - Impact of follicular aspiration on folliculogenesis as influenced by dietary
      energy and stage of lactation.
AB  - Prolonged dietary energy restriction has been shown to influence the secretion of
      ovarian hormones and follicular development. Energy balance affects the ability
      of the cow to support a functional reproductive system during early lactation.
      Follicular aspiration is a tool that can be used to assess the impact of dietary
      energy and stage of lactation on follicle development in dairy cattle. Follicular
      aspiration was conducted twice weekly from d 30 to 100 postpartum in cows fed
      either 104 or 80% of NRC energy requirements. Oocyte numbers recovered increased
      linearly from d 30 to 100 postpartum. Cows on high energy diets produced more
      high quality oocytes, but also produced more poor quality oocytes than cows fed
      the lower energy diet. Follicles < 5 mm predominated throughout. Cows in early (d
      28) and mid (d 117) lactation were used to assess stage of lactation effects on
      serum and follicular fluid hormones, and quality of oocytes recovered by
      follicular aspiration procedures for 10 wk. Serum IGF-1 decreased in early
      lactation cows, but increased in midlactation cows. Follicular fluid progesterone
      in early lactation cows decreased from 275 to 235 ng/ml, whereas in midlactation
      cows it increased from 65 to 550 ng/ml at aspiration wk 10. The percentage of
      high quality ova was higher in early lactation cows (11%) than midlactation cows
      (6%), but fell to 1% by aspiration wk 7 and increased to 10% by wk 10, whereas
      percentage of high quality ova in midlactation cows steadily declined to 2% by wk
      10. Milk yield and energy balance affect patterns of folliculogenesis in
      lactating dairy cows.

PMID- 10908067
TI  - Regulation of ovarian follicular growth by somatotropin and insulin-like growth
      factors in cattle.
AB  - Somatotropin (ST), insulin-like growth factor (IGF)-I, and IGF-II affect animal
      growth and lactation as well as animal reproduction. Understanding the effects of
      ST and the IGF on reproduction is important because ST and IGF-I undergo dynamic
      changes prior to the postpartum breeding period. In addition, administration of
      recombinant bovine somatotropin (rbST) to lactating cows is a common practice
      that increases blood concentrations of ST and IGF-I during the breeding period.
      In vivo, administration of rbST caused greater ovarian follicular development.
      The effects of rbST may represent direct actions of ST because ST receptors are
      found within granulosa cells as well as oocytes. Alternatively, the actions of ST
      may be indirectly mediated by increased IGF-I and (or) nutrient partitioning that
      occurs after rbST. Both IGF-I and IGF-II are synthesized within the ovary.
      Ovarian IGF are, therefore, a composite of IGF from both endocrine (liver) and
      autocrine and paracrine (ovary) sources. The IGF stimulate ovarian function by
      acting synergistically with gonadotropins to promote growth and steroidogenesis
      of ovarian cells. Actions of IGF-I and -II are restrained by a series of IGF
      binding proteins (IGFBP) that either originate from the blood or are synthesized
      locally within the follicle. Degradation and differential synthesis of IGFBP are
      important mechanisms regulating IGFBP amounts. The relative amounts of IGFBP may
      ultimately determine ovarian IGF action. Future studies of ST and IGFs should
      focus on the hormones, receptors, and binding proteins as well as the metabolic
      requirements for normal ovarian function in dairy cattle.

PMID- 10908068
TI  - Historical perspective of turnover of dominant follicles during the bovine
      estrous cycle: key concepts, studies, advancements, and terms.
AB  - This review chronicles the key concepts, studies, advancements and terms that
      have led to our current understanding of turnover of dominant follicles (growth
      and atresia) during the bovine estrous cycle. The "two-wave" concept of
      follicular development was first proposed in 1960, but remained controversial for
      the next 28 yr. The concept of the "dominant" follicle was adapted to cattle in
      1987. By 1988, ultrasound analysis of individual follicles had demonstrated that
      heifers usually had two or three distinct waves of turnover of dominant follicles
      during an estrous cycle. From 1992 to 1993, it was established that a transient
      rise in serum concentrations of FSH initiated each follicular wave, and a
      decreased episodic secretion of LH was associated with loss of dominance and the
      end of a nonovulatory follicular wave. In the past decade, numerous
      intrafollicular growth factors, such as inhibins, activins, and insulin-like
      growth factors and their binding proteins, have been identified in follicular
      fluid of individual bovine follicles. In addition, in vitro studies demonstrate
      that these growth factors could have endocrine, autocrine, or paracrine actions
      that modify gonadotropin-stimulated follicular growth and differentiation.
      However, the precise role of intrafollicular growth factors in turnover of
      dominant follicles has not been defined. We concluded that two or three FSH
      stimulated waves of follicular growth usually occur during the bovine estrous
      cycle, and each follicular wave culminates in development of a single
      nonovulatory or ovulatory dominant follicle.

PMID- 10908069
TI  - Johne's disease and milk: do consumers need to worry?
AB  - Mycobacterium paratuberculosis, an acid-fast bacillus that causes enteritis in
      ruminants, has been suggested as an etiological agent of Crohn's disease in
      humans. The mode of transmission is unclear; however, some evidence suggests that
      humans may become infected via contaminated milk. Currently, it is not known
      whether commercial pasteurization effectively kills M. paratuberculosis in
      contaminated raw milk. Using a laboratory-scale pasteurizer unit designed to
      simulate the high-temperature, short-time method (72 degrees C, 15 sec) currently
      used by commercial dairies, we previously demonstrated that treatment of raw milk
      inoculated with 10(4) to 10(6) cfu of M. paratuberculosis/ml reduced numbers to
      an undetectable level. However, M. paratuberculosis is an intracellular pathogen
      that resides within the macrophages of the host and evades destruction. We
      subsequently performed further experiments examining heat treatment of milk
      inoculated with mammary gland macrophages containing ingested M.
      paratuberculosis. Heat treatment of these samples under high-temperature, short
      time conditions demonstrated that the macrophage does not protect the organism
      because we were unable to recover any viable M. paratuberculosis from the
      samples. Conversely, other researchers have demonstrated that a residual
      population of M. paratuberculosis may survive heat treatment of milk. In
      addition, a recent news report stated that viable M. paratuberculosis organisms
      have been cultured from retail-ready milk in Ireland. A summary of past and
      current studies concerning this issue along with a discussion of methodologies
      used to recover M. paratuberculosis from experimentally inoculated milk will be
      presented in this paper.

PMID- 10908070
TI  - Why do we think? Consequences of regarding thinking as behavior.
AB  - Cognitive psychologists have made significant progress in explaining how people
      think. However, relatively little time and energy have been invested in
      understanding why we think--the factors that make us start or stop thinking,
      choose and change strategies and solutions. Such questions are linked to
      motivation and to discriminative and reinforcing stimuli. In this article, the
      idea that studying thinking as a form of behavior closely connected to antecedent
      stimuli and consequences leads to potentially important questions that are not
      presently being studied in the field of cognitive psychology. This is not an
      argument for reverting to behaviorism--rather, the argument is made that
      integrating a behavioral perspective on thinking would enrich cognitive
      psychology.

PMID- 10908071
TI  - Treating dementia: the complementing team approach of occupational therapy and
      psychology.
AB  - Dementia is a chronic progressive disorder that necessitates an interdisciplinary
      team approach to provide the highest quality of health care. The purpose of this
      article is to describe and promote the collaboration of psychologists and
      occupational therapists as key interdisciplinary team members. Multiple sources
      were referenced to develop and describe an interdisciplinary team model.
      Occupational therapists possess skills in understanding function, maximizing
      residual strengths, defining small changes, modifying the environment, and
      developing caregiver strengths and compensations. These skills can complement the
      skills of psychologists in understanding behavior and emotion, developing
      behavioral interventions, supporting team development, and providing psychosocial
      support to caregivers.

PMID- 10908072
TI  - Family relationships, leaving home, and adjustment to military service.
AB  - Associations between family relationships and individual adjustment were studied
      within a sample of 19-year-old soldiers during their first weeks of basic
      training. Results showed that family relationships partly explained soldiers'
      closeness to best friends, number of social nominations, and commanders' ratings
      of soldiers' military and social competence. In addition, family relations
      explained soldiers' perceived social competence as assessed via closeness to best
      friends and number of sociometric nominations. Together, the results reiterate
      the role played by the family and attitudes toward offspring leaving home and
      toward their adjustment to military service.

PMID- 10908073
TI  - Common method variance and specification errors: a practical approach to
      detection.
AB  - The purpose of this study was to demonstrate how examining the bivariate
      correlations between items in self-report measures can assist in differentiating
      between possible common method variance vs. model specification errors.
      Specifically, social desirability was viewed as either a possible source of
      common method variance or as a theoretically meaningful construct that should be
      included in the model of interest (i.e., a specification error). In the first
      instance, LISREL was used, and the level of correlation between measures of
      social desirability and measures of the five constructs of interest was
      manipulated. These results provided some insight as to when one needs to be
      concerned about the possible "common variance effects" on the structural model.
      In the second instance, the correlations between measures of social desirability
      and the measures of only two constructs of interest were again manipulated. These
      analyses illustrated the point at which the omission of social desirability as a
      theoretically relevant variable began to result in a poor fit of the structural
      model.

PMID- 10908074
TI  - Identity structure, narrative accounts, and commitment to a volunteer role.
AB  - Degree of commitment was explored in relation to core self and role-identity.
      Thirty-one American emergency medical technicians (EMTs) described themselves in
      the EMT role (EMT now) and the way they anticipated they would be in the future
      (EMT future) by selecting items from an adjective checklist. Participants also
      described "real me," "ideal me," and "ought me." Ratings of commitment and
      extranormative activity were also obtained. Finally, participants described a
      positive and a negative episode they had experienced as an EMT in an open-ended
      question that was coded for task and relational content. Each participant's
      checklist data set was individually analyzed using HICLAS, a clustering algorithm
      for binary data (P. DeBoeck, S. Rosenberg, & I. Van Mechelen, 1993). Results
      indicate that the similarity between EMT now and real me best predicted activity
      and the similarity between EMT future and real me best predicted commitment
      (positive correlations in both cases). Older, more experienced EMTs tended to
      describe positive episodes in relational terms, whereas younger, less experienced
      EMTs described positive experiences in task-oriented terms.

PMID- 10908075
TI  - The role of subordinate authoritarianism in cross-level extra-role relationships.
AB  - This study is an investigation of the moderating role of subordinate
      authoritarianism in the relationship between cross-level (i.e., supervisor and
      subordinate) extrarole (i.e., outside of work) activities and job satisfaction
      and organizational citizenship behaviors. Low authoritarian subordinates reported
      greater job satisfaction than high authoritarian subordinates when they
      participated in off-the-job activities with supervisors. The implications of this
      research are discussed.

PMID- 10908076
TI  - Culture and beliefs about time: comparisons among black Americans, black
      Africans, and white Americans.
AB  - The authors investigated the extent to which racial factors, cultural factors, or
      both influence a person's beliefs about physical time, personal time, and
      experienced and remembered duration. A total of 750 Black American, Black
      African, and White American students responded to a questionnaire on these
      beliefs about time. Factor analysis was used to compare belief structures.
      Pairwise comparisons, performed separately for each statement, tested the
      direction and strength of the reported beliefs. The groups showed many
      similarities, but they also showed some differences. All 3 groups differed in
      beliefs about physical and personal time, but they did not differ in beliefs
      about duration experiences. This evidence does not support simplistic views of
      racial or cultural influences. Culture may differentially influence beliefs about
      physical time and personal time. Beliefs about duration experiences may represent
      an ethnic factor that transcends cultures.

PMID- 10908077
TI  - Romantic acts as a correlate of social desirability, neuroticism, and
      extraversion.

PMID- 10908078
TI  - Lumpers versus splitters.

PMID- 10908080
TI  - Sudden death and the electrophysiological effects of angiotensin-converting
      enzyme inhibitors.

PMID- 10908081
TI  - Comparative responsiveness of Short-Form 12 and Minnesota Living With Heart
      Failure Questionnaire in patients with heart failure.
AB  - BACKGROUND: The Short-Form 12 (SF-12) and Living With Heart Failure Questionnaire
      (LHFQ) are commonly used to measure quality of life (QOL) in heart failure
      outcomes research. Their comparative responsiveness, however, has not been
      documented. METHODS AND RESULTS: A prospective cohort study was conducted among
      patients attending a university-based heart failure clinic between April 1997 and
      September 1998. All patients received comprehensive heart failure care
      management. QOL of patients was assessed by the SF-12 and LHFQ at baseline and 3
      months. Of 87 patients completing follow-up, the mean change score was 10.1 for
      the LHFQ and 5.8 for the SF-12 (both Ps < .001). The change scores of the
      instruments were correlated (r = 0.61; P < .001). The SF-12 had a greater ability
      than the LHFQ to statistically detect change in physical health but was less
      sensitive to changes in mental health. The LHFQ performed better than the SF-12
      in the ability to distinguish the differences in perceived global health
      transition. CONCLUSION: The LHFQ is more responsive than the SF-12 to changes in
      QOL. The SF-12 should not be used alone to measure the changes in QOL of patients
      with heart failure.

PMID- 10908079
TI  - Electrophysiological changes of angiotensin-converting enzyme inhibition after
      myocardial infarction.
AB  - To investigate whether prevention of remodeling would translate into a more
      stable electrophysiological profile, the investigators randomized 56 patients to
      treatment with angiotensin-converting enzyme (ACE) inhibition or placebo for 3
      months after myocardial infarction. Programmed electrical stimulation revealed no
      significant differences in inducibility of monomorphic sustained ventricular
      tachycardia (VT), whereas ventricular fibrillation (VF) tended to be lower in the
      ACE-inhibitor group. Effective refractory periods were consistently longer, and
      dispersion of refractoriness was significantly shorter in the ACE-inhibitor
      group. The investigators conclude that in this small patient group ACE inhibition
      may mildly add to a more stable electrophysiological profile.

PMID- 10908082
TI  - Atrium as a source of brain natriuretic polypeptide in patients with atrial
      fibrillation.
AB  - BACKGROUND: Plasma brain natriuretic polypeptide (BNP) levels have been used as
      biochemical markers of systolic left ventricular (LV) dysfunction. Although in
      vitro studies have shown the existence of BNP messenger RNA in the atria, the
      main production site of BNP is believed to be the ventricle. The hypothesis that
      the atrium could be a source of BNP was examined in patients with lone atrial
      fibrillation (AF), the most common type of sustained arrhythmia. METHODS AND
      RESULTS: We studied 16 controls and 21 patients with lone AF. Plasma samples for
      BNP were selectively and serially obtained from the aorta, anterior
      interventricular vein (AIV), and coronary sinus (CS). Atrial natriuretic
      polypeptide (ANP) levels were also measured to determine whether the CS samples
      contained significant amounts of atrial venous drainage. Of the 3 sample
      locations, the CS had the greatest ANP levels, confirming transcatheter sampling
      position accuracy. BNP levels were significantly greater in the CS than AIV in
      the patients with AF (279 +/- 226 v 126 +/- 97 pg/mL; P < .01). Consequently,
      plasma BNP levels were also greater in the patients with AF than controls (103 +/
      90 v 5 +/- 2 pg/mL; P < .001). LV ejection fraction was significantly less in
      patients with AF than control patients. Atrial production of BNP decreased
      significantly after successful DC cardioversion of AF in the 5 restudied patients
      (182 +/- 139 v 59 +/- 64 pg/mL; P < .05). CONCLUSION: The data suggest that AF is
      a condition in which BNP is produced in the atrium itself.

PMID- 10908083
TI  - Plasma norepinephrine and atrial natriuretic peptide in heart failure: influence
      of felodipine in the third Vasodilator Heart Failure Trial. V-HeFT III
      investigators.
AB  - BACKGROUND: Reflex activation of the sympathetic nervous system by short-acting
      dihydropyridine calcium channel antagonists has been reported to harm
      hypertensive patients. Different neurohormonal profiles and their response to
      treatment may influence the effectiveness of dihydropyridine vasodilator
      treatment of heart failure. METHODS: Four hundred fifty men with left ventricular
      (LV) systolic dysfunction were administered standard heart failure treatment and
      felodipine extended release (ER) or placebo in the Vasodilator Heart Failure
      Trial III (V-HeFT III). Plasma norepinephrine (PNE) levels, atrial natriuretic
      peptide (ANP) levels, exercise capacity, LV ejection fraction (EF), cardiac
      dimensions and function, and arrhythmia frequency were measured. Hospital-free
      survival for baseline neurohormonal classes was assessed. RESULTS: Distributions
      of ANP and PNE levels at baseline in patients with heart failure of ischemic and
      nonischemic causes were virtually identical. ANP levels at baseline were
      inversely related to LVEF (r = -0.39; P = .0001), exercise duration (r = -0.19; P
      = .0001), and peak oxygen consumption (r = -0.27; P = .008) and directly related
      to LV (r = 0.23; P = .0006) and right ventricular dilatation (r = 0.23; P =
      .0008). The increase in ANP levels between baseline and 3 months (P = .02) and 1
      year (P = .03) was significantly less in the felodipine-ER group than in the
      placebo group, but PNE levels did not differ between treatment groups. Hospital
      free survival was directly related to baseline ANP (P = .0002) and PNE levels (P
      = .004). All-cause mortality was related to baseline PNE levels (P = .02) but not
      baseline ANP levels. CONCLUSION: Levels of ANP and PNE hormones are related to LV
      dysfunction, exercise performance, and hospital-free survival in heart failure
      and PNE levels are related to all-cause mortality. Treatment with felodipine ER
      did not adversely affect survival in any neurohormone subclass.

PMID- 10908084
TI  - Unsaturated aldehydes including 4-OH-nonenal are elevated in patients with
      congestive heart failure.
AB  - BACKGROUND: Lipid peroxidation generates several unsaturated aldehydes, such as 4
      OH-nonenal (HNE), which may interact with and modify the function of other
      molecules that are of biological importance. Although congestive heart failure
      (CHF) is a state of generalized oxidative stress, the resultant spectrum of
      saturated and unsaturated aldehydes has not been systematically characterized in
      this condition. METHODS: We studied 8 CHF patients and 8 age-matched patients
      with normal left ventricular (LV) function. The concentrations of 22 aldehydes
      produced by lipid peroxidation, including saturated (n-alkanals) and unsaturated
      (t-2-alkenals, t-2,t-4-alkadienals, 4-OH-alkenals) aldehydes, were measured in
      arterial plasma by gas chromatography mass spectrometry (GC/MS). LV contractility
      (+dP/dt) and relaxation (Tau) were directly measured with a micromanometer-tipped
      catheter. RESULTS: Compared with patients who have normal LV function, CHF
      patients had higher levels of total aldehydes (9,311 +/- 835 v 6,594 +/- 344
      nmol/L, P < .01), as well as multiple unsaturated aldehydes (t-2-alkenals and 4
      OH-alkenals, including HNE). In the CHF group, a strong relationship was observed
      between total aldehyde concentration and both +dP/dt (correlation coefficient = 
      0.76, P < .05) and Tau (correlation coefficient = 0.78, P < .05). CONCLUSION:
      Unsaturated aldehyde levels were consistently elevated in the plasma of CHF
      patients compared with patients who have normal LV function. In CHF patients,
      elevated aldehyde levels were associated with impairment of LV contractility.

PMID- 10908085
TI  - Beta-blockade in adriamycin-induced cardiomyopathy.
AB  - Beta-blockade consistently improves myocardial systolic function in patients with
      both nonischemic and ischemic cardiomyopathy. The effects of beta-blockade on
      Adriamycin-induced cardiomyopathy (ACM), however, are unknown. We retrospectively
      evaluated the effects of beta-blockade on patients with ACM by using a case
      controlled design. The control group consisted of 16 consecutively chosen age-
      and sex-matched patients with idiopathic dilated cardiomyopathy (IDC) who were
      treated with beta-blockers. Patients with ACM had a baseline mean left
      ventricular ejection fraction (LVEF) of 28%, which improved to 41% (P = .041)
      after treatment with beta-blockers. The control group had a baseline mean LVEF of
      26%, which improved to 32% (P = .015) after treatment. The mean duration of beta
      blocker therapy in the Adriamycin and control groups was 8 and 9 months,
      respectively. The degree of improvement between the 2 groups was not
      significantly different. Beta-blockers have a beneficial effect on cardiac
      function in patients with ACM, which is at least comparable with other forms of
      heart failure with systolic dysfunction.

PMID- 10908086
TI  - Differential responses of circulating and tissue adrenomedullin and gene
      expression to volume overload.
AB  - BACKGROUND: Adrenomedullin (AM), which is produced by various tissues and organs,
      also circulates in the blood. Circulating AM levels increase during disease
      states such as essential hypertension, heart failure, and renal failure. However,
      little is known about how circulating AM or AM production responds to volume
      overload (VOL). METHODS AND RESULTS: Progressive VOL was induced in rats by an
      aortocaval shunt (AC) or by an aortocaval shunt with banding of the abdominal
      aorta distal to the shunt (AC + B), which created a larger shunt volume. Plasma
      and tissue AM concentrations, as well as AM gene expression levels, were measured
      at 1, 5, and 14 days after operation. Plasma concentrations of atrial natriuretic
      peptide (ANP), aldosterone, and renin activity (PRA) were also examined.
      Pulmonary congestion, pleural effusion, and ascites rapidly progressed in the AC
      + B group, suggesting that VOL caused more rapid heart failure under these
      conditions. Plasma AM concentrations in the AC + B and AC groups at day 1
      compared with those in sham-operated rats were increased by 300% and 140%,
      respectively, and then gradually declined. The time course of plasma AM over 14
      days was similar to that of plasma aldosterone and PRA, but not of plasma ANP or
      intracardiac filling pressure. The increase in plasma AM was accompanied by
      upregulated AM gene expression in the lung and aorta and by decreased AM
      concentrations in the atrium, ventricle, and adrenal gland. Cardiac AM gene
      expression levels were increased in the hypertrophied ventricles of AC and AC + B
      rats. CONCLUSIONS: The major findings of the present study were 1) a rapid
      increase in plasma AM after the imposition of VOL in association with increased
      plasma aldosterone and PRA, 2) the contribution of several organs to this
      increase, and 3) a late increase in the AM messenger RNA (mRNA) level in the
      ventricles as VOL-induced ventricular hypertrophy developed.

PMID- 10908087
TI  - Plasma amino-terminal pro-brain natriuretic peptide: a novel approach to the
      diagnosis of cardiac dysfunction.
AB  - BACKGROUND: Heart failure is a common cause of hospitalization and death across
      the industrialized world. Improving the diagnosis and care of patients with heart
      failure is therefore likely to have a major impact on morbidity, mortality, and
      health care costs. METHODS AND RESULTS: To determine the relation between cardiac
      function and plasma levels of amino-terminal brain natriuretic peptide precursor
      (NT-proBNP), plasma NT-proBNP levels and ventricular function (by radionucleotide
      ventriculography) were measured in healthy patients, patients with renal failure,
      patients with recent myocardial infarction, and patients investigated for
      cardiorespiratory symptoms. Plasma NT-proBNP levels were greater in healthy women
      (median, 1.5 fmol/mL; range, 1.0 to 13.8 fmol/mL; n = 34) than healthy men
      (median, 1.0 fmol/mL; range, 1.0 to 3.3 fmol/mL; n = 33; P = .012). NT-proBNP
      levels were elevated in subjects with renal failure (geometric mean, 314 fmol/mL;
      range, 18 to 5,800 fmol/mL) and were related to left ventricular ejection
      fraction (LVEF) (r = -0.86; P < .0001; n = 19). NT-proBNP levels were also
      related to LVEF in patients with recent myocardial infarction (r = -0.62; P =
      .0003; n = 29) and those investigated for cardiorespiratory symptoms (r = -0.56;
      P < .0001; n = 129). Applying an upper limit of normal of 5 fmol/mL for men and
      15 fmol/mL for women (specificity, 100%), elevated plasma NT-proBNP levels had
      100% sensitivity for the detection of LVEF less than 45% after myocardial
      infarction and 97% sensitivity for the detection of LVEF less than 45% in
      patients investigated for cardiorespiratory symptoms. NT-proBNP levels were also
      elevated in 87% of the patients with normal systolic function (LVEF > or = 45%)
      after myocardial infarction and in 87% of the patients investigated for
      cardiorespiratory symptoms with heart failure and normal systolic function (LVEF
      > or = 45%). CONCLUSIONS: Plasma NT-proBNP level is a sensitive indicator of
      cardiac dysfunction, both in the presence and absence of systolic dysfunction,
      and may prove to be a useful tool for the identification and management of
      cardiac dysfunction in the general community.

PMID- 10908088
TI  - An ovine model of chronic stable heart failure.
AB  - BACKGROUND: Chronic stable large animal models of heart failure are difficult to
      establish. We report an ovine model of chronic stable heart failure achieved by a
      technique of repetitive myocardial infarctions (one of the most common causes of
      cardiac failure) with catheter-based techniques. METHODS AND RESULTS: Ejection
      fraction (EF) was assessed by echocardiography. A perfusion catheter was
      positioned in either the left anterior descending or circumflex artery by using
      standard angioplasty techniques. Myocardial infarction was induced by a Gelfoam
      embolism via this catheter and was confirmed by electrocardiographic (ECG)
      changes and new segmental abnormalities. The procedure was repeated at 2 weekly
      intervals until the EF was less than 40%. Target EF was achieved in 15 animals,
      with a mean of 3.4 embolizations (range 2 to 8). Baseline EF was 68%, with a mean
      final EF of 33%. This resulted in a 54% reduction in EF (range 44% to 68%) from
      baseline values. Two animals developed late symptomatic heart failure and died,
      whereas EF was stable at 3-month follow-up echocardiography in the remaining
      animals with no significant spontaneous improvement. CONCLUSION: Chronic stable
      heart failure can be established in sheep with catheter-based skills and a
      microembolization technique that causes repetitive myocardial infarctions.

PMID- 10908089
TI  - Inotropic and energetic effects of altering the force-calcium relationship:
      mechanisms, experimental results, and potential molecular targets.
AB  - Conventional positive inotropy with beta-adrenergic agonists or phosphodiesterase
      inhibitors increases the amplitude of the calcium transient and is associated
      with increases in myocardial oxygen consumption that may not be desirable when
      used in heart failure. Alternatively, agents that increase the sensitivity of the
      contractile apparatus without increasing the amplitude of the calcium transient
      have been shown to increase contractility without increasing energy consumption.
      Also, agents that result in negative inotropy while maintaining the amplitude of
      the calcium transient result in more energy-inefficient negative inotropy in
      comparison with agents that cause negative inotropy though a decrease in the
      amplitude of the calcium transient. These experiments suggest that calcium
      handling is responsible for a large proportion of the total energy expenditure
      associated with changes in inotropy. Problems that remain with the use of calcium
      sensitizing agents include uncertainty regarding the site of action, adverse
      effects on systemic and coronary vasculature and diastolic function, and
      concomitant phosphodiesterase-inhibiting activity. One alternative is to use
      genetically engineered mouse models in which specific mutations selective to the
      myocyte can be produced. Potential molecular targets include the protein kinase A
      and C phosphorylation sites on troponin I, which, when phosphorylated, mediate a
      reduction in calcium sensitivity and a reduction in maximal actomyosin
      adenosinetriphosphatase activity, respectively. Mutations at these sites, by
      altering the relationship between force and calcium, may provide significant
      insights into the molecular mechanisms controlling the energetics of positive
      inotropy.

PMID- 10908091
TI  - What does ATLAS really tell us about "high" dose angiotensin-converting enzyme
      inhibition in heart failure?
AB  - The Assessment of Treatment with Lisinopril and Survival (ATLAS) results have
      been widely quoted by proponents advocating the use of "high" doses of
      angiotensin-converting enzyme (ACE) inhibitors for the treatment of heart
      failure. In ATLAS, however, the relative benefits of "high" versus "low" dose ACE
      inhibition were small. Intermediate doses of ACE inhibitors proven effective in
      previous placebo-controlled trials provide benefit that appears likely to equal
      or exceed the benefit from "high" dose ACE inhibition. Therefore, we recommend
      that physicians continue to prescribe ACE inhibitors for patients with heart
      failure based on the target doses used in the placebo-controlled trials and not
      on the "high" dose target used in ATLAS.

PMID- 10908090
TI  - Noninvasive methods for detecting elevated left-sided cardiac filling pressure.
AB  - Knowledge of left-sided cardiac filling pressures has an important role in the
      management of patients with chronic heart failure. However, the use of a
      pulmonary artery catheter to measure pulmonary capillary wedge pressure is
      generally reserved for hospitalized patients with decompensated heart failure,
      leaving only noninvasive means of estimating left heart pressures in the majority
      of patients. Unfortunately, the routine clinical evaluation of patients with
      chronic systolic heart failure lacks the sensitivity and specificity needed to
      accurately assess left atrial pressure. In this review, we focus on noninvasive
      methods that can reliably predict left-sided filling pressures and may have
      clinical application in the ambulatory setting.

PMID- 10908093
TI  - Mechanistic and clinical rationales for using beta-blockers in heart failure.
AB  - In the 1980s and early 1990s, evidence suggesting a pivotal role for chronic
      neurohormonal stimulation in the pathophysiology of heart failure began to
      emerge, which has now produced a dramatic change in the way heart failure is
      viewed and treated. Preclinical data and results from clinical trials revealed
      that blocking the actions or generation of norepinephrine or angiotensin II
      positively affected the course of left ventricular dysfunction and myocardial
      failure, despite the fact that this inhibition had minimal or negative effects on
      hemodynamics. Angiotensin-converting enzyme (ACE) inhibitors have been used for
      heart failure for many years, but only recently have beta-blockers been
      recommended as part of standard treatment for heart failure. The negative
      inotropic effects of beta-blockers are well known; these agents must be used with
      caution in patients with heart failure. However, after several months of
      treatment, left ventricular ejection fraction (LVEF) gradually increases, and a
      reversal of the pathological remodeling associated with chronic heart failure
      occurs: left ventricular mass decreases, chamber shape becomes more elliptical,
      and mitral regurgitation decreases. Data from clinical trials have shown that
      long-term beta-adrenergic blockade halts the progression of pump dysfunction,
      substantially improves left ventricular function, and reduces morbidity and
      mortality rates in patients with mild-to-moderate heart failure. This article
      provides a detailed rationale for the use of beta-blockers in patients with
      chronic heart failure, based on the current understanding of pathophysiology and
      recent clinical trial data.

PMID- 10908092
TI  - Adrenergic overload and apoptosis in heart failure: implications for therapy.
AB  - Sympathetic nervous system activity to the myocardium is increased in patients
      with heart failure. It is now appreciated that norepinephrine (NE), the primary
      sympathetic neurotransmitter, can exert direct adverse effects on cardiac
      myocytes and might thereby contribute to pathological remodeling, a chronic
      process which leads to progressive left ventricular (LV) chamber dilation and
      loss of contractile function. The demonstration of apoptosis in failing human
      hearts has led to the thesis that continuing loss of viable myocytes is a
      mechanism for progressive myocardial failure. For many years it has been
      appreciated that chronic exposure to catecholamines can exert a toxic effect on
      the myocardium. In vitro studies in cultured cardiac myocytes show that tonic
      exposure to NE increases the number of apoptotic myocytes via stimulation of the
      beta-adrenergic receptor (beta-AR) pathway. Interestingly, a beta1-AR selective
      antagonist completely prevented NE-stimulated apoptosis, whereas a beta2-AR
      selective antagonist increased the amount of apoptosis, suggesting that beta1-
      versus beta2-AR may couple to different signaling pathways. In rats,
      isoproterenol infusion for as little as 12 hours increased the frequency of
      terminal deoxynucleotidyltransferase-mediated nick end-labeling (TUNEL)-positive
      myocytes. Likewise, mice that overexpress beta1-AR or G alpha s in the myocardium
      develop left ventricular dilation, contractile dysfunction and apoptosis.
      Although the link between apoptosis and myocardial failure remains to be proven,
      these in vitro and in vivo observations provide a rational mechanism by which
      beta-AR antagonists may help to prevent or slow LV remodeling and failure in
      patients.

PMID- 10908094
TI  - The impact of beta-blockade on mortality rates in patients with congestive heart
      failure.
AB  - The beneficial effects of beta-adrenergic blockade on mortality rates in patients
      after a myocardial infarction have been clear for decades. The efficacy data are
      now just as apparent for patients with heart failure. Although there are many
      subgroups of patients in whom the mortality effects of beta-blockers are not
      proven, knowledge about these specific populations continues to increase.
      Nevertheless, more information is needed so that we can properly tailor our
      therapy for individual patients.

PMID- 10908095
TI  - The role of beta-blockers in preventing sudden death in heart failure.
AB  - Sudden death accounts for one third to one half of the deaths in patients with
      heart failure. Recent studies using beta-adrenergic blockers in patients with
      reduced systolic function and heart failure symptoms have shown significant
      reductions in overall mortality rates. This article discusses the role of beta
      blockers in preventing sudden death in these patients. Six large beta-blocker
      trials in patients with heart failure have been published to date, with a
      combined relative risk reduction for sudden death of 38% (confidence interval
      [CI] 0.53-0.23; P < .001). Although dependent on a nonmechanistic definition of
      sudden death, the clinical trials of beta-blockers to date have shown that they
      significantly reduce the risk of sudden death in patients with heart failure.
      Future studies are required to define the role of other heart failure therapies
      in the context of this new standard of care.

PMID- 10908096
TI  - From clinical trials to clinical practice: what we know and do not know about
      beta-blockers and the heart.
AB  - In the early 1980s, several lines of evidence suggested the possibility that
      decreasing adrenergic drive could be beneficial in patients with chronic heart
      failure. Clinical trials conducted in the 1990s have unequivocally shown that
      beta-blockade improves left-ventricular ejection fraction (LVEF) in the failing
      heart. Beta-blockers represent the only medical treatment that has been shown to
      reverse the pathological myocardial remodeling observed in patients with chronic
      heart failure. Beta-blockers are now a mainstay of therapy for patients with New
      York Heart Association (NYHA) class II and III heart disease; however, several
      issues remain unresolved regarding beta-blocker treatment of heart failure,
      including (1) the potential role of beta-blockers in asymptomatic (NYHA class I)
      patients; (2) the potential role of beta-blockers in patients with severe (NYHA
      class IV) heart failure; (3) the possibility of more rapid dose titration; and
      (4) the influences of sex, age, and race. Further studies evaluating the efficacy
      of beta-blockade in class I and class IV patients are forthcoming; the results of
      these trials will help to determine the role of beta-blocker therapy in patients
      at the extremes of heart failure (ie, asymptomatic patients and those with
      advanced heart failure). This article discusses the issues that still remain
      regarding the transitioning of beta-blockade from clinical trials to clinical
      practice and indicates areas in which further research is warranted. Finally,
      barriers to treatment are discussed as well as possible strategies for overcoming
      these obstacles.

PMID- 10908097
TI  - Clinical use of beta-blockers in patients with heart failure.
AB  - Recognition of the role of the sympathetic nervous system in chronic heart
      failure has resulted in dramatic changes in the way heart failure is viewed,
      providing strong evidence for the therapeutic role for beta-adrenergic blocking
      agents. This treatment strategy does not provide short-term hemodynamic
      improvement and may even worsen symptoms initially. However, beta-blockers can be
      administered with good or even excellent tolerability by slowly withdrawing
      adrenergic support to the failing heart. Results of clinical trials have shown
      that long-term treatment with beta-blockers improves ventricular function and
      reduces mortality rates in patients with mild-to-moderate heart failure. Although
      the improvement in ventricular function is a beta-blocker class effect, there are
      distinct differences in antiadrenergic activity and tolerability among the first
      , second-, and third-generation agents. These differences--as well as practical
      strategies for dose titration and the management of decompensation--are the focus
      of this article.

PMID- 10908098
TI  - Occupational coronary heart disease among bridge and tunnel officers.
AB  - Traffic-control officers employed in New York City tunnels prior to 1981 have
      been at increased risk of mortality from coronary heart disease. In this study,
      the authors assessed current coronary heart disease prevalence and evaluated
      associations between coronary heart disease and occupational factors among New
      York City bridge and tunnel officers. A clinical cardiovascular disease
      surveillance and cross-sectional occupational epidemiologic study was conducted.
      The authors used comprehensive evaluations to identify current and prior
      incidences of coronary heart disease. Occupational risk factors evaluated
      included job strain, current and historic exposure to carbon monoxide, and
      occupational physical inactivity. Current carbon monoxide exposure was assessed
      via workshift changes in carboxyhemoglobin. Coronary heart disease occurred in 29
      (5.5%) of the 526 bridge and tunnel officers examined. Risk of coronary heart
      disease was associated positively with total years each bridge and tunnel officer
      work had worked in that capacity (odds ratio = 1.64 for each decade of
      employment, adjusted for nonoccupational coronary heart disease risk factors).
      Carboxyhemoglobin levels were low in the subjects, and job strain and physical
      inactivity were very prevalent. Occupational factors contributed to the risk of
      coronary heart disease in New York City bridge and tunnel officers. The authors
      were unable to identify the specific factors that led to the increase in risk
      described.

PMID- 10908099
TI  - Psychiatric inferences from data on psychologic/psychiatric symptoms in multiple
      chemical sensitivities syndrome.
AB  - When abnormal psychologic/psychiatric symptom data are obtained on personality
      tests or psychiatric interviews administered to patients who report symptoms of
      Multiple Chemical Sensitivities Syndrome, investigators typically attribute these
      to either psychiatric traits or to psychogenic origins of illness. The primary
      purpose of these studies was the evaluation of the plausibility of nonpsychiatric
      explanations of psychologic/psychiatric symptom data. In Study 1, patients with
      Multiple Chemical Sensitivities Syndrome used the Minnesota Multiphasic
      Personality Inventory 2 (MMPI-2) to describe which items had changed after they
      developed the condition. In Study 2, three diverse groups of professionals
      predicted which items on the MMPI-2 might change after a mentally healthy person
      developed the Syndrome or a condition resembling it. In Study 3, a second sample
      of Multiple Chemical Sensitivities Syndrome patients completed the MMPI-2 and
      other questionnaires by mail, which allowed the authors to ascertain whether
      these patients showed more or different psychopathology than was described by
      patients and hypothesized by professionals. Data from Study 1 patient informants
      indicated that developing the syndrome might result in a psychopathological MMPI
      2 profile, characterized by abnormal Hypochondriasis and Hysteria scale scores.
      Professionals in Study 2 showed a consensus about hypothesized MMPI-2 changes
      following the development of the syndrome. These changes likely elevated the
      Hypochondriasis, Hysteria, Psychasthenia, Depression, and Schizophrenia scale
      scores. In Study 3, the patients taking the MMPI-2 showed elevations on the
      Hypochondriasis, Hysteria, Depression (women only), and Schizophrenia scales.
      Abnormal scores were associated closely with greater severity of illness and
      greater adjustment to illness. The strategy of administering psychometric tests
      to ill populations for the purposes of evaluating psychiatric illness or traits,
      and/or psychogenic origins of illness was shown to be potentially misleading.

PMID- 10908100
TI  - 1,1,1-trichloro-2,2-bis (p-chlorophenyl)-ethane (DDT) and reduced bone mineral
      density.
AB  - The organochlorine pesticide 1,1,1-trichloro-2,2-bis (p-chlorophenyl)-ethane
      (DDT), is a well-known and widely dispersed "environmental estrogen" (World
      Health Organization Criteria no. 9; Geneva, Switzerland [1979]). Kelce et al.
      (Nature, 1995; 375:581-85) recently identified the DDT metabolite, 1,1-dichloro
      2,2-bis(p-chlorophenyl)ethylene (DDE), has also recently been identified as a
      potent androgen receptor antagonist. The authors examined the relationship
      between serum levels of DDE and bone mineral density in 68 sedentary women who
      reported adequate dietary intake of calcium. Reduced bone mineral density was
      correlated significantly with age (r = -.36, p = .004), as well as with increases
      in the log of DDE levels in serum (r = -.27, p = .03). The authors also used
      multiple-regression analysis to examine the influence of other predictor
      variables on the relationship between log DDE and bone mineral density. The
      strongest model (p = .002) included log DDE (p = .018), age (p = .002), and years
      on hormone replacement therapy (p = .10) as predictor variables, and this model
      afforded prediction of 21% of bone mineral density variation. These results
      suggest that past community exposures to DDT may be associated with reduced bone
      mineral density in women.

PMID- 10908101
TI  - Health status and internal radiocontamination assessment in children exposed to
      the fallout of the Chernobyl accident.
AB  - The Chernobyl fallout caused release of radioisotope contaminants in a very large
      area that includes Belarus, the Ukraine, and the Russian Federation. In this
      study, the authors monitored the health status and level of internal
      contamination in 422 children who resided in the aforementioned areas and who
      were < or = 10 y of age at the time of the accident. The children came to Italy
      for a 1-mo period between 1991 and 1992. During this time, the children underwent
      pediatric checkups and biochemical, immunological, and thyroid analyses. All
      children underwent whole-body counter measurements, and urine radiotoxicological
      analysis was performed for 224 of them. The 24 children evacuated from Pripiat, a
      village very close to the Chernobyl reactor site, were selected for cytogenetic
      analysis. All of these children continue to have a detectable internal
      contamination of caesium radioisotopes. This condition is likely the result of
      ground and foodstuff contamination in the various areas. The children did not
      evidence overt pathologies related to ionizing radiation. However, minor
      alterations in immunological and thyroid parameters were observed in the group of
      the evacuated children. Traditional cytogenetic dosimetry was not possible, but
      the occurrence of acentric fragments was observed-indicating a persistent effect
      of continuous exposure to low doses of radiation.

PMID- 10908102
TI  - Maternal exposure to trichloroethylene in drinking water and birth-weight
      outcomes.
AB  - An ecological epidemiological study was conducted with data obtained from an
      environmental dose-reconstruction study and the Arizona Birth Information Tapes.
      Before 1981, a portion of the city of Tucson water-distribution system was
      contaminated with trichloroethylene (i.e., < 5 micrograms per liter of water to
      107 micrograms per liter of water). Target and comparison populations were
      selected with a Geographic Information System. Logistical-regression analysis
      revealed an association between maternal exposure to trichloroethylene via
      drinking water and very-low-birth-weight babies (i.e., < 1,501 grams) (odds ratio
      = 3.3; 95% confidence interval = 0.5, 20.6; and Wald chi-square p value = 0.2).
      No association was found between maternal exposure to trichloroethylene via
      drinking water and low birth weight or full-term low-birth-weight infants
      (gestational period > 35 wk and < 46 wk).

PMID- 10908103
TI  - Correlations among human plasma levels of dioxin-like compounds and
      polychlorinated biphenyls (PCBs) and implications for epidemiologic studies.
AB  - In studies of the potential health effects of background-level exposure to
      organochlorine compounds (e.g., polychlorinated biphenyls, polychlorinated
      dibenzodioxins, and polychlorinated dibenzofurans), investigators have often
      measured either polychlorinated biphenyls or polychlorinated
      dibenzodioxins/polychlorinated dibenzofuransbut not both. We measured
      polychlorinated biphenyls (including specific non-, mono-, and di-ortho
      congeners) and specific polychlorinated dibenzodioxins/dibenzofurans among 63
      Canadian blood donors. Levels of these compounds were, in general, fairly
      correlated. For example, Pearson's correlation coefficient between log total
      polychlorinated biphenyl and log total polychlorinated dibenzodioxins was .52.
      These results suggest that in epidemiologic studies of health effects of
      background-level exposures to these compounds, the quantitative dose-response
      relation observed for a given compound (or class of compounds acting through a
      similar mechanism) may easily be miscalibrated or confounded.

PMID- 10908104
TI  - Analysis of indoor concentrations of benzene using an air-quality model.
AB  - We performed measurements to determine indoor benzene levels in 26 residential
      houses in Kuwait, located in zones of different activity levels. Pumped (or
      active) sampling was conducted via use of 12 sampling tubes over a period of 24
      hr for both indoor and outdoor concentrations simultaneously. Time-average indoor
      concentration varied linearly with time-average outdoor concentration in
      accordance with a mass-balance-based indoor air-quality model in which source and
      sink terms were incorporated. We used regression analysis to determine benzene
      adsorption rates, which appear in the removal and source terms of the model. The
      removal rate parameter varied between 0.12/hr and 2.16/hr, whereas source term
      parameter varied between 0.60 mg/hr and 76.07 mg/hr. Houses were then divided
      into three groups according to their benzene source strengths (i.e., < 1.0 mg/hr,
      1-10 mg/hr, and 10-50 mg/hr). Qualitatively, these levels depended on the
      characteristics of occupants (e.g., smoking and gas cooker use, number of cars,
      and parking area) and location of the building.

PMID- 10908105
TI  - Respiratory effects of seasonal exposures to ozone and particles.
AB  - Whereas human respiratory effects of brief ozone exposures are well documented,
      much less is known about the human health effects of mid- to long-term exposures.
      The authors' objective in this study was to determine whether lung function or
      respiratory symptom changes would occur over the course of a summer season among
      healthy young adults working outdoors in the presence of ozone. The authors
      studied 72 sophomore cadets from the U.S. Military Academy at West Point, New
      York, 21 of whom attended special summer training in Fort Dix, New Jersey, an
      area characterized by elevated ozone levels; the remaining cadets attended
      training in areas with moderate ozone levels (i.e., Fort Benning, Georgia; Fort
      Leonard Wood, Missouri; and Fort Sill, Oklahoma). The authors hypothesized that
      adverse respiratory outcomes, if any, would be more pronounced in the group
      exposed to higher ozone levels. Spirometry was performed and respiratory symptoms
      were assessed-both before and after the summer-in a clinic at West Point. Time
      spent outdoors during summer training averaged 11 hr/d. Both mean and peak ozone
      levels were higher at Fort Dix than at the three remaining sites. Regional levels
      of sulfur dioxide and particulate matter less than 10 microm in aerodynamic
      diameter were relatively low during the study. However, all cadets reported
      frequent exposure to dust, exhaust, and smoke in the course of their training.
      Averaged across all subjects, there was a statistically significant drop in
      forced expiratory volume in 1 sec of 44 ml (p = .035) over the summer. There were
      also significant increases in reports of cough, chest tightness, and sore throat
      at the follow-up clinic visit. A larger mean forced expiratory volume in 1 sec
      decline was observed at Fort Dix, where ozone exposures were the highest. The
      results of this study demonstrated a seasonal decline in respiratory function
      among healthy young adults working outdoors in the presence of ozone and
      particulate matter.

PMID- 10908107
TI  - WF14865A and B, new cathepsins B and L inhibitors produced by Aphanoascus
      fulvescens. I. Taxonomy, production, purification and biological properties.
AB  - WF14865A and B, novel cathepsins B and L inhibitors, were produced and isolated
      separately from the culture mycelium of a fungal strain Aphanoascus fulvescens
      No. 14865. Spectroscopic analysis revealed that both WF14865A and B were composed
      of trans-epoxysuccinyl moieties, 1-H-imidazole-2-ylamine, and isoleucine or
      leucine. These compounds inhibited human cathepsins B and L with IC50 values in
      the range of 8.4 approximately 72nM in vitro. Though their in vitro properties
      were typical as trans-epoxysuccinyl type inhibitors, they exerted strong bone
      resorption inhibitory effects in low-calcium-diet-fed mouse model at 3.2
      approximately 10 mg/kg.

PMID- 10908106
TI  - Lead-glazed ceramic ware and blood lead levels of children in the city of Oaxaca,
      Mexico.
AB  - Although Mexico substantially reduced use of leaded gasoline during the 1990s,
      lead-glazed pottery remains a significant source of population exposure. Most
      previous studies of lead in nonoccupationally exposed groups in Mexico have been
      conducted in the Mexico City metropolitan area. Oaxaca, a poor southern state of
      Mexico, has a centuries-old tradition of use of low temperature lead-glazed
      ceramic ware manufactured mainly by small family businesses. We measured blood
      lead levels in 220 8-10-y-old children (i.e., not from pottery-making families)
      who were students in the innercity of Oaxaca and in the mothers of all children.
      The geometric mean blood lead level of the children was 10.5 microg/dl (+7.0/-4.3
      microg/dl standard deviation; range = 1.3-35.5 microg/dl). The corresponding mean
      value for the mothers was 13.4 (+9.0/-5.4 microg/dl standard deviation; range =
      2.8-45.3 microg/dl). We used cutoffs that were greater than or equal to 10
      microg/dl, 20 microg/dl, and 30 microg/dl, and we determined that 54.9%, 10.3%,
      and 3.0% of the children were at or above the respective criteria. We accounted
      for 25.2% of the variance in blood lead levels of the children, using maternal
      responses to a questionnaire that assessed possible lead sources in a linear
      multiple-regression model. The most important factors related to lead levels were
      family use of lead-glazed pottery, use of animal fat in cooking, and family
      income. The addition of maternal blood lead level to the model increased
      accounted variance in blood lead to 48.0%. In logistic-regression modeling of
      children's blood lead levels, we used a cutoff of greater than or equal to 10
      microg/dl, and we found that use of lead-glazed pottery was the most important of
      all questionnaire items that were predictive of blood lead levels (odds ratio =
      2.98). In Oaxaca, as is the case elsewhere in Mexico, lead-glazed ceramic ware
      remains a significant risk factor for elevated blood lead levels in children.

PMID- 10908108
TI  - F-12509A, a new sphingosine kinase inhibitor, produced by a discomycete.
AB  - In the course of our screening for inhibitors of sphingosine kinase, we found an
      active compound from a culture broth of a discomycete, Trichopezizella barbata
      SANK 25395. The structure of the compound, named F-12509A, was elucidated by a
      combination of spectroscopic analyses, to be a new sesquiterpene quinone
      consisting of a drimane moiety and a dihydroxybenzoquinone. Enzyme kinetic
      analyses showed that F-12509A inhibits sphingosine kinase activity in a
      competitive manner with respect to sphingosine, with a Ki value of 18 microM.

PMID- 10908109
TI  - (2R-trans)-2-butyl-5-heptylpyrrolidine as a potent sigma receptor ligand produced
      by Streptomyces longispororuber.
AB  - A potent sigma (sigma) receptor ligand was isolated from the culture broth of
      Streptomyces longispororuber #525. The active compound was identified to be (2R
      trans)-2-butyl-5-heptylpyrrolidine by spectroscopic and chemical studies. The
      compound exhibited high affinity and selectivity for sigma receptors. The IC50
      values toward sigma1, sigma2 and dopamine D2 receptors were 2.0, 22.7 and more
      than 40,000 nM, respectively. Its (2S-trans)- and (+/-)-cis-isomers, both
      synthesized, were also found to be high affinity sigma ligands.

PMID- 10908110
TI  - IB-96212, a novel cytotoxic macrolide produced by a marine Micromonospora. I.
      Taxonomy, fermentation, isolation and biological activities.
AB  - A novel bioactive macrolide, IB-96212 has been isolated from the fermentation
      broth of a marine actinomycete, L-25-ES25-008. The strain belongs to the genus
      Micromonospora. The macrolide showed a very strong cytotoxic activity against P
      388, and lower but significant activity against A-549, HT-29, and MEL-28 cell
      lines. We describe the isolation, taxonomy and fermentation of the producing
      strain as well as the isolation of IB-96212.

PMID- 10908111
TI  - IB-96212, a novel cytotoxic macrolide produced by a marine Micromonospora. II.
      Physico-chemical properties and structure determination.
AB  - IB-96212, is a new member of spiroketal containing macrolide class of
      fermentation-derived natural products isolated from mycelial extracts of
      Micromonospora sp. The structure consists of a new aglycone which possesses a 26
      membered macrolide ring system and of one deoxy sugar identified as L-rhodinose,
      this structure represents the first reported spiroketal macrolide natural product
      related to other macrolides, such as oligomycins, dunaimycins, citovaricin,
      rutamycin and ossamycin.

PMID- 10908112
TI  - Thioesterases and the premature termination of polyketide chain elongation in
      rifamycin B biosynthesis by Amycolatopsis mediterranei S699.
AB  - The role of two thioesterase genes in the premature release of polyketide
      synthase intermediates during rifamycin biosynthesis in the Amycolatopsis
      mediterranei S699 strain was investigated. Creation of an in-frame deletion in
      the rifR gene led to a 30 approximately 60% decrease in the production of both
      rifamycin B by the S699 strain or a series of tetra- to decaketide shunt products
      of polyketide chain assembly by the rifF strain. Since a similar percentage
      decrease was seen in both genetic backgrounds, we conclude that the RifR
      thioesterase 2 is not involved in premature release of the carbon chain assembly
      intermediates. Similarly, fusion of the Saccharopolyspora erythraea DEBS3
      thioesterase I domain to the C-terminus of the RifE PKS subunit did not result in
      a noticeable increase in the amount of the undecaketide intermediate formed nor
      in the amounts of the tetra- to decaketide shunt products. Hence, premature
      release of the carbon chain assembly intermediates is an unusual property of the
      Rif PKS itself.

PMID- 10908113
TI  - Identification of inhibitors of inducible nitric oxide synthase from microbial
      extracts.
AB  - A new member of the angucycline family, vineomycin C (3), together with four
      known metabolites saquayamycin A1 (1), A-7884 (2), rabelomycin (5) and
      xanthomegnin (6) were isolated from microbial extracts. The structures were
      determined by 1D and 2D NMR techniques and chemical degradation. Compounds 1-3
      and 5 were isolated from a fermentation of Streptomyces sp., while 6 was isolated
      from a fungal fermentation extract. All five compounds have shown potent
      inhibitory activity in the inducible nitric oxide synthase (iNOS) assay.

PMID- 10908114
TI  - Cloning, characterization and heterologous expression of a polyketide synthase
      and P-450 oxidase involved in the biosynthesis of the antibiotic oleandomycin.
AB  - The gene cluster encoding the deoxyoleandolide polyketide synthase (OlePKS) was
      isolated from the oleandomycin producing strain Streptomnyces antibioticus.
      Sequencing of the first two genes encoding OlePKS, together with the previously
      identified third gene revealed an overall genetic and protein architecture
      similar to that of the erythromycin gene cluster encoding the 6
      deoxyerythronolide B synthase (DEBS) from Saccharopolyspora erythraea. When the
      entire OlePKS (10,487 amino acids) was expressed in the heterologous host
      Streptomyces lividans, it produced 8,8a-deoxyoleandolide, an aglycone precursor
      of oleandomycin. The role of the P-450 monooxygenase, OleP, in oleandomycin
      biosynthesis was also examined in vivo by co-expression with DEBS in S. lividans.
      The production of 8,8a-dihydroxy-6-deoxyerythronolide B and other derivatives
      indicates that OleP is involved in the epoxidation pathway of oleandomycin
      biosynthesis. Since there are currently no genetic systems available for
      manipulation of the natural oleandomycin producing strain, the heterologous
      expression system reported here provides a useful tool for studying this
      important macrolide antibiotic.

PMID- 10908116
TI  - Macrolide esterase-producing Escherichia coli clinically isolated in Japan.
AB  - Current Japanese clinical practice involves the usage of large amounts of new
      macrolides such as clarithromycin and roxithromycin for the treatment of diffuse
      panbronchiolitis, Helicobacter pylori and Mycobacterium avium complex infections.
      In this study, the phenotypes, genotypes, and macrolide resistance mechanisms of
      macrolide-inactivating Escherichia coli recovered in Japan from 1996 to 1997,
      were investigated. The isolation rate of erythromycin A highly-resistant E. coli
      (MIC > or = 1,600 microg/ml) in Japan slightly increased from 0.5% in 1986 to
      1.2% in 1997. In six macrolide-resistant strains, recovered from the strains
      collected for this study during 1996 to 1997, the inactivation of macrolide could
      be detected with or without added ATP in the assay system. The appearance of
      erythromycin A-inactivating enzyme independent of ATP was novel from Japanese
      isolates, and the 1H NMR spectra of oleandomycin hydrolyzed by the three ATP
      independent isolates were examined. It was clearly shown that the lactone ring at
      the position of C-13 was cleaved as 13-H signal in aglycon of oleandomycin upper
      shifted. These results suggested the first detection of macrolide-lactone ring
      hydrolase from clinical isolates in Japan. These results suggested the first
      detection of an ATP-independent macrolide-hydrolyzing enzyme from Japanese
      clinical isolates. Substrate specificity of the macrolide-hydrolyzing enzyme was
      determined with twelve macrolides including the newer members of this group and
      it was found that not only erythromycin A but also the new macrolides, such as
      clarithromycin, roxithromycin, and azithromycin were inactivated. The NMR data,
      broad spectrum of activity, and independence of co-enzyme supported our naming of
      the enzyme as a macrolide esterase. PCR methodology was employed to detect an
      ereB-like gene from the 3 isolates producing macrolide esterase, and one of these
      was subsequently shown to contain both ereB-like and ermB-like genes. It was also
      clearly shown that the other three isolates, which inactivated macrolide in the
      presence of ATP, had an mphA-like gene.

PMID- 10908115
TI  - The potent immunosuppressive cyclosporin FR901459 inhibits the human P
      glycoprotein and formyl peptide receptor functions.
AB  - By sequestering cytosolic calcineurin into a molecular complex with cyclophilin
      and its consequent T-cell dysfunction, some cyclosporins, such as CsA and
      FR901459 ([Thr2-Leu5-Leu10]-CsA), display potent immunosuppressive activity.
      Independently on this property, cyclosporins may display one or more other
      biological activities mediated by interaction with cell surface glycoproteins.
      Several cyclosporins inhibit the function of human MDRI-encoded P-glycoprotein
      (Pgp), a flippase known to cause cancer multidrug resistance, but also expressed
      by some normal immunocompetent cells and by normal epithelial cells which control
      drug bioavailability in vivo. CsA is known to be a potent Pgp inhibitor with a
      3.2 microM IC50 in an assay where the most potent derivative SDZ PSC 833 gives a
      0.49 microM IC50. FR901459 is now shown to be a good Pgp inhibitor, being 2-fold
      weaker only (IC50 of 6 microM) than CsA. Some cyclosporins may also inhibit the
      function of the human FPR1-encoded formyl peptide receptor (FPR), a chemotactic
      receptor whose absence is known to impair antibacterial immunity. Yet this
      inhibition is very weak for all, but one of them, CsH, whose 0.15 micro/M IC50
      makes it a much more potent FPR inhibitor than CsA (IC50 >10 microM in the same
      assay). FR901459 is now shown to be a very potent inhibitor of FPR function (IC50
      of 0.6 microM). Since CsH shows little Pgp-inhibitory activity and has no known
      immunosuppressive activity, FR901459 displays a unique pharmacological profile:
      like CsA, it inhibits T-cell function; less than CsA, it can inhibit Pgp function
      on selected leukocyte subsets and on epithelial barriers known to control drug
      bioavailability; however, much more efficiently than CsA, it can inhibit the FPR
      function, a receptor involved in some leukocytic inflammatory responses to
      chemotactic peptides.

PMID- 10908117
TI  - Glomosporin, a novel antifungal cyclic depsipeptide from Glomospora sp. II.
      Structure elucidation.
AB  - The structure of glomosporin, an antifungal antibiotic, was elucidated by NMR and
      MS spectroscopic studies. Glomosporin is a novel cyclic depsipeptide with an
      amino acid sequence Ser-Ala-Asp-Asn-Asn-Ser-Thr, and a 3,4-dihydroxy-4
      methylhexadecanoic acid side chain.

PMID- 10908118
TI  - Preparation and antimicrobial activity of micacocidin.
AB  - Micacocidin (3), a Zn-free derivative of micacocidin A (1), was prepared to
      evaluate its antimicrobial activity in comparison with 1 and to obtain a starting
      material for chemical modification of 1. The structure of 3, quite unlike those
      of any previously known antimicrobial agents, was elucidated by 1-D and 2-D
      homonuclear and heteronuclear NMR and mass spectroscopy. Micacocidin (3) thus
      prepared exhibited weak or no antibacterial activity except against Mycoplasma
      species, i.e. 3 showed stronger activity than 1. It is noteworthy that 3
      displayed high activity against fungi such as Candida, Aspergillus and
      Trichophyton species.

PMID- 10908119
TI  - Synthesis of pironetin and related analogs: studies on structure-activity
      relationships as tubulin assembly inhibitors.
AB  - Pironetin (1) and demethylpironetin (2) are potent inhibitors of tubulin
      assembly. They arrested the mammalian cell cycle in M-phase and showed antitumor
      activity against a murine tumor cell line, P388 leukemia, transplanted in mice.
      To investigate the chemical and biological properties of 1, we synthesized
      several derivatives and investigated the structure-activity relationships. All
      synthesized derivatives decreased biological activities, such as inhibition of
      cell cycle progression, and disruption of the microtubule network in situ. The
      most drastic decrease was observed in 6, 8 and 10. These results suggested that
      alpha,beta-unsaturated lactone, chirality at the 7-position bearing a hydroxyl
      group and the terminal portion of the alkyl chain are important for microtubule
      inhibitory activity of pironetins.

PMID- 10908120
TI  - Novel cephalosporins 1. Synthesis of 3-benzothiopyranylthiovinyl cephalosporins
      and antibacterial activity against methicillin-resistant Staphylococcus aureus
      and vancomycin-resistant Enterococcus faecalis.

PMID- 10908121
TI  - Novel cephalosporins 2. Synthesis of 3-heterocyclic-fused thiopyranylthiovinyl
      cephalosporins and antibacterial activity against methicillin-resistant
      Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis.

PMID- 10908122
TI  - Circadian clocks: what makes them tick?
AB  - In the not too distant past, it was common belief that rhythms in the physical
      environment were the driving force, to which organisms responded passively, for
      the observed daily rhythms in measurable physiological and behavioral variables.
      The demonstration that this was not the case, but that both plants and animals
      possess accurate endogenous time-measuring machinery (i.e., circadian clocks)
      contributed to heightening interest in the study of circadian biological rhythms.
      In the last few decades, flourishing studies have demonstrated that most
      organisms have at least one internal circadian timekeeping device that oscillates
      with a period close to that of the astronomical day (i.e., 24h). To date, many of
      the physiological mechanisms underlying the control of circadian rhythmicity have
      been described, while the improvement of molecular biology techniques has
      permitted extraordinary advancements in our knowledge of the molecular components
      involved in the machinery underlying the functioning of circadian clocks in many
      different organisms, man included. In this review, we attempt to summarize our
      current understanding of the genetic and molecular biology of circadian clocks in
      cyanobacteria, fungi, insects, and mammals.

PMID- 10908123
TI  - Pacemaker oscillations in heart and brain: a key role for hyperpolarization
      activated cation channels.
AB  - Rhythmic activity of single cells or multicellular networks is a common feature
      of all organisms. The oscillatory activity is characterized by time intervals of
      several seconds up to many hours. Cellular rhythms govern the beating of the
      heart, the swimming behavior of sperm, cycles of sleep and wakefulness,
      breathing, and the release of hormones. Many neurons in the brain and cardiac
      cells are characterized by endogenous rhythmic activity, which relies on a
      complex interplay between several distinct ion channels. In particular, one type
      of ion channel plays a prominent role in the control of rhythmic electrical
      activity since it determines the frequency of the oscillations. The activity of
      the channels is thus setting the "pace" of the oscillations; therefore, these
      channels are often referred to as "pacemaker" channels. Despite their obvious
      important physiological function, it was not until recently that genes encoding
      pacemaker channels have been identified. Because both hyperpolarization and
      cyclic nucleotides are key elements that control their activity, pacemaker
      channels have now been designated hyperpolarization-activated and cyclic
      nucleotide-gated (HCN) channels. The molecular identification of the channels and
      the upcoming studies on their properties in heterologous systems will certainly
      enhance our understanding of "pacemaking" in physiological systems. This review
      gives a brief insight into the physiological importance of these channels and
      sums up what we have learned since the first cloning of genes succeeded (for
      recent reviews, see also Clapham 1998; Luthi and McCormick 1998a; Biel et al.
      1999; Ludwig, Zong, Hofmann, et al. 1999; Santoro and Tibbs 1999).

PMID- 10908124
TI  - Circadian control of migratory restlessness and the effects of exogenous
      melatonin in the brambling, Fringilla montifringilla.
AB  - Circadian pacemakers control both "daytime" activity and nocturnal restlessness
      of migratory birds, and the daily rhythm of melatonin release from the pineal has
      been suggested to be involved in the control of migratory activity. To study the
      phase relations between the two activity components during entrainment and when
      free running, locomotor activity of bramblings (Fringilla montifringilla) was
      recorded continuously under a 12:12 "cool light" to "warm light" cycle (CL:WL,
      ca. 5,000 K and ca. 2,500 K, respectively) or blue light to red light cycle
      (BL:RL. maxima at 440 and 650 nm, respectively) at different irradiance ratios.
      Migratory activity was expressed primarily during the WL or RL phase of the light
      cycles. Under free-running conditions, the circadian periods tau correlated with
      the phase relations between day and night (migratory) activity components during
      preceding entrainment. Bramblings with migratory activity had significantly
      longer tau at constant light intensity than the same individuals without
      migratory activity. Birds with migratory activity reentrained faster after a 6h
      phase shift of the CL:WL cycle than birds without migratory activity. When
      exogenous melatonin was given in the drinking water (200 microg/mL 1% ethanol or
      0.86 mM) to bramblings exposed to 12:12 CL:WL cycles with constant irradiance,
      the amounts of activity, which were initially higher during the WL phase of the
      light cycle, were suppressed to similar low levels during both light phases. The
      systematic changes in the amounts of activity during melatonin treatment were not
      correlated with consistent changes in entrainment status. The data support the
      hypothesis that changes in the amplitude and level of the daily melatonin cycle
      are involved in regulating migratory restlessness, by either allowing or
      inhibiting nocturnal activity.

PMID- 10908125
TI  - Sleep and circadian phase characteristics of adolescent and young adult males in
      a naturalistic summertime condition.
AB  - Our aim was to compare the circadian phase characteristics of healthy adolescent
      and young adult males in a naturalistic summertime condition. A total of 19
      adolescents (mean age 15.7 years) and 18 young adults (mean age 24.5 years) with
      no sleep problems took part in this study. Two-night polysomnographic (PSG) sleep
      recordings and 24h secretion patterns of urinary 6-sulfatoxymelatonin were
      monitored in all 37 subjects. Sleep-wake patterns were initially assessed at home
      using a standard sleep diary. Circadian assessment included the measure of dim
      light melatonin offset (DLMOff) and the morningness-eveningness (M/E)
      questionnaire. As expected, compared to young adults, adolescents habitually
      spent more nocturnal time in bed and spent more time (and percentage) in delta
      sleep. No difference was found between adolescents and young adults on multiple
      sleep latency test (MSLT) sleep onset latencies, M/E, melatonin secretion
      measures (24h total, nighttime, daytime, and night ratio), and DLMOff. For the
      subjects as a whole, correlational analyses revealed a significant association
      between the DLMOff and M/E and between both these phase markers and habitual
      bedtimes, habitual rising times, and melatonin secretion measures (daytime levels
      and the night ratio). No association was found between phase markers and daytime
      sleepiness or sleep consolidation parameters such as sleep efficiency or number
      of microarousals. These results together indicate that adolescents and young
      adults investigated during summertime showed similar circadian phase
      characteristics, and that, in these age groups, an evening phase preference is
      associated with a delayed melatonin secretion pattern and delayed habitual sleep
      patterns without a decrease in sleep consolidation or vigilance.

PMID- 10908126
TI  - Seasonal variation in heart rate variability in asthmatic children.
AB  - Asthma is a "seasonal disease" with symptoms either aggravated by environmental
      changes during specific seasons or prevalent at certain times of the year for
      other reasons. We examined whether the heart rate variability (HRV) of asthmatic
      children changes by season. The HRV during a portion of one night (00:00-04:00)
      and day (12:00-16:00) and the entire 24h period (00:00-24:00) during each of the
      four seasons was analyzed. The data of 95 children with asthma and 106 healthy
      children, as controls, were assessed. In children with asthma during the 24h
      period, seasonal variation in the low-frequency (LF) band (0.04-0.15 Hz) and the
      high-frequency (HF) band (0.15-0.4 Hz) were detected (HF: F=6.81, p=.0003; LF:
      F=4.18, p= .008). The HF value in the summer was significantly higher than in
      autumn and spring (Scheffe test: autumn vs. summer, s = 4.46, p < .001: spring
      vs. summer, s = 2.86, p < .05), while the LF value in autumn was significantly
      lower than in summer (s = 3.42, p < .01). In the control group, no seasonal
      variation in HF, LF, or LF/HF was detected. The findings infer the HRV, a
      surrogate measure of autonomic nervous system function, of asthmatic children is
      more susceptible to seasonal changes brought about by either endogenous annual
      rhythms or environmental weather phenomena.

PMID- 10908127
TI  - Circadian rhythm in peak expiratory flow: alteration with nocturnal asthma and
      theophylline chronotherapy.
AB  - We investigated changes in the circadian rhythm of peak expiratory flow (PEF) in
      seven persons with nocturnal asthma for a 24h span when (1) they were symptom
      free and their disease was stable, (2) their asthma deteriorated and nocturnal
      symptoms were frequent, and (3) they were treated with theophylline
      chronotherapy. Subjects recorded their PEF every 4h between 07:00 and 23:00 one
      day each period. Circadian rhythms in PEF were assessed using the group-mean
      cosinor method. The circadian rhythm in PEF varied according to asthma severity.
      Significant circadian rhythms in PEF were detected during the period when asthma
      was stable and when it was unstable and nocturnal symptoms were frequent. When
      nocturnal symptoms were present, the bathyphase (trough time) of the PEF rhythm
      narrowed to around 04:00; during this time of unstable asthma, the amplitude of
      the PEF pattern increased 3.9-fold compared to the symptom-free peiiod. No
      significant group circadian rhythm was detected during theophylline
      chronotherapy. Evening theophylline chronotherapy proved to be prophylactic for
      persons whose symptoms before treatment had occurred between midnight and early
      morning. Changes in the characteristics of the circadian rhythm of PEF,
      particularly amplitude and time of bathyphase, proved useful in determining when
      to institute theophylline chronotherapy to avert nocturnal asthma symptoms.

PMID- 10908128
TI  - Implementation of 12-hour shifts in a Brazilian petrochemical plant: impact on
      sleep and alertness.
AB  - A recent worldwide trend in chemical and petrochemical industries is to extend
      the duration of shifts. Optimization of the labor force to reduce costs is one
      reason to increase the length of working time in a shift. Implementation of 12h
      shifts is a controversial decision for managers and scientists. Literature
      reviews show alertness is lower during the nighttime hours, and sleep duration is
      reduced and worse during the daytime. The main objective of this study was to
      evaluate the impacts of 12h shifts on alertness and sleep. To evaluate the
      duration and quality of sleep and alertness during work, 22 male shift workers on
      a continuous rotating schedule at a petrochemical plant completed activity logs
      and estimated alertness using analog 10-cm scales for 30 consecutive days, three
      times (at 2h, 6h, and 10h of the shift) every work shift. Statistical tests
      (analysis of variance [ANOVA] and Tukey) were performed to detect differences
      between workdays and off days. The shift schedule was 2 days/3 nights/4 off days,
      followed by 3 days/2 nights/5 off days, followed by 2 days/2 nights/5 off days.
      Sleep duration varied significantly (p < .001) among the work shifts and off
      days. Comparing work nights, the shortest mean sleep occurred after the second
      night (mean = 311.4 minutes, SD = 101.7 minutes), followed by the third night
      (mean = 335.3 minutes, SD = 151.2 minutes). All but one shift (sleep after the
      first work night) were significantly different from sleep after the first 2
      workdays (p < .002). Tukey tests showed no significant differences in sleep
      quality between workdays and nights, with the exception of sleep after the third
      day compared to sleep after night shifts. However, significant differences were
      detected between off days and work nights (p < .01). ANOVA analysis showed
      borderline differences among perceived alertness during day shifts (p = .073) and
      significant differences among the hours of the shifts (p = .0005), especially
      when comparing the 2nd hour of the first day with the 10th hour of all the day
      shifts. There were no significant differences in perceived alertness during night
      work among the first, second, and third nights (p = .573), but there were
      significant differences comparing the times (2nd, 6th, 10th hour) of the night
      shifts (p < .001). The evaluation of sleep (duration and quality) and level of
      alertness have been extensively used in the literature as indicators of possible
      performance decrements at work. The results of this study show poorer sleep after
      and significantly decreased alertness during night work. Shifts of 12h are
      usually implemented for technical and economic reasons. These results point out
      the necessity of a careful trade-off between the financial and technical gains
      longer shifts might bring and the possible losses due to incidents or accidents
      from performance decrements during work.

PMID- 10908129
TI  - A comparison of some different methods for purifying core temperature data from
      humans.
AB  - Nine healthy females were studied about the time of the spring equinox while
      living in student accommodations and aware of the passage of solar time. After 7
      control days, during which a conventional lifestyle was lived under a 24h
      "constant routine," the subjects lived 17 x 27h "days" (9h sleep in the dark and
      18h wake using domestic lighting, if required). Throughout the experiment,
      recordings of wrist activity and rectal (core) temperature were taken. The raw
      temperature data were assessed for phase and amplitude by cosinor analysis and
      another method, "crossover times," which does not assume that the data set is
      sinusoidal. Two different purification methods were used in attempts to remove
      the masking effects of sleep and activity from the core temperature record and so
      to measure more closely the endogenous component of this rhythm; these two
      methods were "purification by categories" and "purification by intercepts." The
      former method assumes that the endogenous component is a sinusoid, and that the
      masking effects can be estimated by putting activity into a number of bands or
      categories. The latter method assumes that a temperature that would correspond to
      complete inactivity can be estimated from measured temperatures by linear
      regression of these on activity and extrapolation to a temperature at zero
      activity. Three indices were calculated to assess the extent to which exogenous
      effects had been removed from the temperature data by these purification methods.
      These indices were the daily variation of phase about its median value; the ratio
      of this variation to the daily deviation of phase about midactivity; and the
      relationship between amplitude and the square of the deviation of phase from
      midactivity. In all cases, the index would decrease in size as the contribution
      of the exogenous component to a data set fell. The purification by categories
      approach was successful in proportion to the number of activity categories that
      was used, and as few as four categories produced a data set with significantly
      less masking than raw data. The method purification by intercepts was less
      successful unless the raw data had been "corrected" to reflect the direct effects
      of sleep that were independent of activity (a method to achieve this being
      produced). Use of this purification method with the corrected data then gave
      results that showed least exogenous influences. Both this method and the
      purification by categories method with 16 categories of activity gave evidence
      that the exogenous component no longer made a significant contribution to the
      purified data set. The results were not significantly influenced by assessing
      amplitude and phase of the circadian rhythm from crossover times rather than
      cosinor analysis. The relative merits of the different methods, as well as of
      other published methods, are compared briefly; it is concluded that several
      purification methods, of differing degrees of sophistication and ease of
      application to raw data, are of value in field studies and other circumstances in
      which constant routines are not possible or are ethically undesirable. It is also
      concluded that such methods are often somewhat limited insofar as they are based
      on pragmatic or biological, rather than mathematical, considerations, and so it
      is desirable to attempt to develop models based equally on mathematics and
      biology.

PMID- 10908131
TI  - Circadian variations of the serum creatine kinase level--a masking effect?
AB  - Since the serum level of the enzyme creatine (phospho)kinase (CPK) is frequently
      used for diagnostic purposes and since circadian variations of this parameter
      have been observed under different stress conditions, it had to be determined
      whether they are induced by an endogenous circadian rhythm or whether they are
      activity-related masking effects. For this purpose, 15 untrained male test
      persons were examined for a period of 25h each under different conditions: lying
      constantly in a climatic chamber, everyday activity conditions, resting
      conditions with intermittent bicycle ergometer tests (1.4 W/kg body weight)
      between 09:00 and 11:30 or between 15:00 and 17:30. In addition, 5 sportsmen were
      included in the study under resting conditions and the bicycle ergometer tests in
      the forenoon. The serum CPK was determined at intervals of 2h or 4h,
      respectively. Under constant resting conditions, the mean serum CPK level
      decreased continuously (p < .001, repeated measures analysis of variance [Rep.
      Mes. ANOVA]), and the final values amounted to approximately 80% of the initial
      values. In contrast, under everyday conditions, the mean CPK level rose during
      the activity phase and decreased again to below the initial values during
      subsequent rest (p < .001, Rep. Mes. ANOVA). In the ergometer tests, the CPK
      blood level rose in each case after the activity phase and fell again
      continuously in the following resting period. However, in the calculation of the
      deviations from the linear trend, it was shown that certain daily variations in
      the CPK values can be detected under constant resting conditions; however, the
      amplitude was much smaller than the amplitude under everyday activity conditions.
      All in all, it can be stated that serum CPK levels are mainly dependent on the
      physical load conditions, and that the daily changes observed under everyday
      conditions disappear almost entirely under resting conditions. The daily
      variation of the serum creatine kinase level under everyday conditions can thus
      be regarded as a masking effect. These results are of practical significance for
      diagnosis to the extent that the physical activity that has taken place before
      the determination of the CPK level must be taken into account in the
      interpretation of the values. According to the results obtained so far, the CPK
      serum level may be used in chronobiology as an indicator of masking by physical
      activity.

PMID- 10908130
TI  - Computation of model-dependent tolerance bands for ambulatorily monitored blood
      pressure.
AB  - The construction of time-specified reference limits requires systematic sampling
      in clinical health, particularly for those variables characterized by a circadian
      rhythm of large amplitude, as it is the case for blood pressure (BP). For the
      detection of false negatives, tolerance intervals (limits that will include at
      least a specified proportion of the population with a stated confidence) are
      important and should substitute when possible for prediction limits. We have
      previously described a nonparametric method for the computation of model
      independent tolerance intervals that are constructed by first dividing the
      sampling range in several time spans in which no appreciable changes in
      population characteristics (namely, mean and variance) take place. The tolerance
      interval is then computed for each of the time spans. The limits thus computed,
      as well as results of any comparison of a given individual's profile against such
      tolerance intervals, are highly dependent on the sampling scheme of both the
      reference individuals and the test subject. To avoid this problem, we have
      developed an alternative method that allows the computation of model-dependent
      tolerance bands for hybrid time series. Assuming that a set X of longitudinal
      series monitored from a given group of reference individuals can be fitted with
      the same individual model, a population model C(X,t) can be also determined, as
      well as the deviation S(X,t) of each individual curve from the population model.
      The tolerance band will then have the form C(X,t) +/- kS(X,t), where k is here
      estimated following a nonparametric approach based on bootstrap techniques.
      Alternatively, two different values of k can be estimated (for the lower and
      upper limits of the tolerance interval, respectively) in cases for which we
      cannot assume symmetry. The method is generally applicable for any population
      model describing the reference population (including the fit of multiple
      significant components, nonsinusoidal waveforms, and/or trends). The method was
      used to establish time-specified tolerance bands for time series of blood
      pressure monitored automatically in healthy individuals of both genders. Model
      dependent intervals are preferred to the model-independent limits when reliance
      on a specified sampling rate needs to be avoided. These limits may serve for an
      objective and positive definition of health, for the screening and diagnosis of
      disease, and for gauging the subject's response to treatment.

PMID- 10908132
TI  - Circadian changes of heart rate in West syndrome.
AB  - Patterns of circadian and ultradian rhythms in the heart rate (HR) are described
      in a full-term baby with birth asphyxia and convulsions. A 24h HR recording was
      carried out at the age of 1, 15, 56, 289, and 295 days; West syndrome diagnosis
      was made when the patient was 3 months old. The HR showed no circadian rhythm in
      the follow-up, whereas it is known that the circadian rhythm appears in healthy
      infants at the age of 1 month and remains thereafter. This observation may be an
      indirect indicator of the interference of West syndrome with centers of
      neurological maturity.

PMID- 10908133
TI  - The prevalence of alcohol, cannabinoids, benzodiazepines and stimulants amongst
      injured drivers and their role in driver culpability: part i: the prevalence of
      drug use in drive the drug-positive group.
AB  - Blood samples from 2,500 injured drivers were analysed for alcohol,
      cannabinnoids, benzodiazepines and stimulants. Overall, three-quarters of drivers
      tested negative for drugs. Alcohol was the most frequently detected drug.
      Cannabinoids were also detected at high rates, but the majority of drivers tested
      positive for THC-acid, the inactive metabolite of THC. Benzodiazepines and
      stimulants were detected at low rates, and detection rates for combinations of
      drugs were also low. Males were more likely to test positive for drugs,
      especially alcohol and THC, whereas females were more likely to test positive for
      benzodiazepines. A similar proportion of car drivers and motorcycle riders tested
      positive for drugs, although riders were more likely to test positive for THC.
      Single-vehicle crashes were particularly associated with alcohol for both car
      driver and riders, and for riders, multiple-vehicle crashes were particularly
      associated with THC.

PMID- 10908135
TI  - Modeling traffic accident occurrence and involvement.
AB  - The Negative Binomial modeling technique was used to model the frequency of
      accident occurrence and involvement. Accident data over a period of 3 years,
      accounting for 1,606 accidents on a principal arterial in Central Florida, were
      used to estimate the model. The model illustrated the significance of the Annual
      Average Daily Traffic (AADT), degree of horizontal curvature, lane, shoulder and
      median widths, urban/rural, and the section's length, on the frequency of
      accident occurrence. Several Negative Binomial models of the frequency of
      accident involvement were also developed to account for the demographic
      characteristics of the driver (age and gender). The results showed that heavy
      traffic volume, speeding, narrow lane width, larger number of lanes, urban
      roadway sections, narrow shoulder width and reduced median width increase the
      likelihood for accident involvement. Subsequent elasticity computations
      identified the relative importance of the variables included in the models.
      Female drivers experience more accidents than male drivers in heavy traffic
      volume, reduced median width, narrow lane width, and larger number of lanes. Male
      drivers have greater tendency to be involved in traffic accidents while speeding.
      The models also indicated that young and older drivers experience more accidents
      than middle aged drivers in heavy traffic volume, and reduced shoulder and median
      widths. Younger drivers have a greater tendency of being involved in accidents on
      roadway curves and while speeding.

PMID- 10908134
TI  - The prevalence of alcohol, cannabinoids, benzodiazepines and stimulants amongst
      injured drivers and their role in driver culpability: part ii: the relationship
      between drug prevalence and drug concentration, and driver culpability.
AB  - Blood samples from 2,500 injured drivers were analysed for alcohol, cannabinoids
      (measured by the presence of THC), benzodiazepines and stimulants. The
      relationship between the prevalence and concentration of drugs and the
      culpability of the driver was examined using an objective method for assessing
      culpability. There were no significant differences between males and females with
      respect to culpability. However, there was a relationship between age and
      culpability: drivers under 26 years and over 60 years were more likely to be
      culpable. Drivers who tested positive for alcohol only, benzodiazepines only and
      the combinations of alcohol and THC and alcohol and benzodiazepines were
      significantly more likely to be culpable for the crash compared with the drug
      free group. Conversely, a lower percentage of drivers who only tested positive
      for THC were culpable for the crash compared with drug-free drivers. This
      difference was not statistically significant. For car drivers in single-vehicle
      crashes, the majority of drivers were judged culpable irrespective of drug use.
      In multiple-vehicle crashes, car drivers testing positive for alcohol only or
      benzodiazepines only were more likely to be culpable for the crash compared with
      drug-free drivers. For motorcycle riders in both single- and multiple-vehicle
      crashes, there were no significant differences between the drug-positive and drug
      free groups. A higher percentage of drug-free riders in multiple-vehicle crashes
      were culpable compared with riders who only tested positive for THC, but this
      difference was not statistically significant. There was a significant
      concentration-dependent relationship between alcohol and culpability: as blood
      alcohol concentration increased, so did the percentage of culpable drivers. When
      THC was used alone, there was no significant increase in culpability. For those
      drivers with benzodiazepines at therapeutic concentrations and above, there was a
      significant increase in culpability. The relationship between stimulants and
      culpability was not significant, although a higher proportion of stimulant
      positive drivers were culpable compared with drug-free drivers. The combinations
      of alcohol and THC, and alcohol and benzodiazepines also produced a significant
      increase in culpability, but this increase was not significantly greater than
      that produced by alcohol alone.

PMID- 10908136
TI  - Traffic accident reduction by monitoring driver behaviour with in-car data
      recorders.
AB  - People who are aware of being observed tend to modify their behaviour. This
      phenomenon could potentially be used to encourage individuals to behave more
      safely when driving if there were means of providing feedback to the drivers
      about their behaviour on the road. So-called 'vehicle data recorders' offer such
      a means of providing behavioural feedback by confronting drivers with their
      recorded driving actions. A field trial of a 'matched experimental/control group
      design with intervention' was planned with the objective of investigating whether
      this feedback mechanism would reduce the number of road traffic accidents in
      everyday driving conditions. In the study, seven experimental vehicle fleets were
      involved, which varied widely in terms of the kind of transport sector concerned,
      the type of vehicles used, and the traffic circumstances in which the vehicles
      are operated. Each fleet was matched with at least one control vehicle fleet,
      taking into account those relevant traffic safety characteristics. In total,
      accident and exposure data were collected for 840 vehicles of which 270 equipped
      with a recorder. During an observation period representing a total of about 3,100
      vehicle years, these vehicles were involved in 1,836 road accidents. Analysis of
      the effects of the use of data recorders in these fleets resulted in an average
      estimated accident reduction of some 20%. The analysis shows that the actual
      savings vary depending on the transport sector involved and on the prior level of
      the fleet's safety record. Further studies are needed to identify the more
      promising application of such a use of traffic data recorders as a means of
      reducing road accidents.

PMID- 10908137
TI  - Demographic and environmental correlates of pedestrian injury collisions: a
      spatial analysis.
AB  - Pedestrian injury collisions often occur when and where large numbers of
      pedestrians travel within complex roadway systems with high traffic flow. The
      pedestrian injury literature suggests a number of individual and environmental
      correlates of injury risks, however studies in this area have primarily focused
      upon demographic differences (e.g. related to age) and a few global
      characteristics of the roadway system (e.g. aspects of pedestrian traffic).
      Studies in which the geography of communities has been considered are primarily
      descriptive, identifying pedestrian injury 'hot spots'. The current study more
      extensively explores some geographic correlates of pedestrian injury collisions
      through a spatial analysis of data from the city of San Francisco, CA. A spatial
      autocorrelation corrected regression model was used to determine factors
      associated with pedestrian traffic injury in 1990. The study used a geographic
      information system to map locations of pedestrian injuries, and environmental and
      demographic characteristics of the city across census tract units. In addition to
      a number of demographic factors (gender, age, marital status, education, income
      and unemployment), it was proposed that several environmental features of the
      city would be related to injury rates (high traffic flow, complex roadway
      systems, greater population densities and alcohol availability). Results of the
      study showed that pedestrian injury rates were related to traffic flow,
      population density, age composition of the local population, unemployment, gender
      and education. Availability of alcohol through bars was directly related to
      pedestrian injury collisions in which the pedestrian had been drinking alcohol.

PMID- 10908138
TI  - Motorcycle engine size and risk of moderate to fatal injury from a motorcycle
      crash.
AB  - Current New Zealand law requires that motorcyclists with a learner or restricted
      licence ride a motorcycle with an engine capacity of 250 cc or less. Previous
      research has reported inconsistent findings regarding the relationship between
      cubic-capacity and risk of a crash. We sought to determine: (1) compliance with
      the law; (2) if the risk of an injury crash is increased for learner/restricted
      licence holders who do not comply with the cubic capacity regulations; and (3)
      whether the risk of an injury crash increases with increasing capacity of the
      motorcycle. A population-based case-control study was conducted in the Auckland
      region over a 3 year period from February 1993. Among the controls, 66% were
      riding motorcycles with a capacity greater than 250 cc. The percentages for those
      with: full, learner and restricted, and no licence were 82, 29 and 60%,
      respectively. There was no evidence that learner and restricted licence holders
      who did not comply with the cubic capacity requirement were at increased risk. It
      should be noted however, that 75% of those who were complying were doing so on
      motorcycles of 250 cc or less. Relative to motorcycles of less than 250 cc the
      risk of an injury crash was elevated by at least 50% for all cubic capacity
      categories, with the exception of the 251-499 group. There was, however, no
      consistent pattern of increasing risk as cubic capacity increased. The findings
      of this study coupled with the fact that cubic capacity is a poor measure of
      power suggest that, if cubic capacity was to remain the sole basis for
      restricting learner and restricted licence holders, consideration should be given
      to having a substantially lower cubic capacity than 250 cc. An analysis of risk
      in terms of power to weight ratio and style of motorcycle may provide a more
      useful insight into the benefits of motorcycle design restrictions for novice
      riders.

PMID- 10908140
TI  - Venturesomeness and extraversion as correlates of juvenile drivers' traffic
      violations.
AB  - Ninety-eight juvenile traffic offenders, 81 men and 17 women, were examined
      regarding the personality traits of extraversion, neuroticism, psychoticism,
      impulsiveness and venturesomeness and compared with a control group of 149
      applicants for driving licences, 82 male and 67 female. The participants of the
      study were administered German translations of the Eysenck personality
      questionnaire (EPQ-R) and the impulsiveness/venturesomeness/empathy questionnaire
      (IVE). Traffic offenders had significantly higher scores on the venturesomeness
      dimension as compared to the control group, and male offenders scored
      significantly higher on extraversion than did male controls. Hypotheses regarding
      a relationship between traffic offences and psychoticism and impulsiveness were
      not confirmed, however. It is concluded that traffic violations in juveniles
      should primarily be viewed within the scope of normal behaviour and do not
      necessarily imply serious personality disorder.

PMID- 10908139
TI  - Detecting intoxicated drivers in Germany -- estimating the effectiveness of
      police tests.
AB  - The most important prerequisite for deterring people from driving while
      intoxicated is to persuade them of the likelihood of being detected by the
      police. Detection requires the police (1) to stop intoxicated drivers and (2) to
      detect the intoxication. The latter is not a simple task in Germany as the police
      is only allowed to obtain a breath sample when indications of an intoxication are
      present. The paper estimates the effectiveness of police tests in detecting
      intoxicated driving by comparing data from the German Roadside Survey and the
      Unterfranken Accident Study to a study of usual police routine and to official
      accident statistics. Both the German Roadside Survey and the Unterfranken
      Accident study were conducted in such a way that breath alcohol testing was
      carried out for nearly every driver, thus giving an estimate of the number of
      intoxicated trips and accidents in Germany. Comparing these numbers to the
      intoxicated trips and accidents detected by the police allows a detailed analysis
      of different components of detection. From those, suggestions are given for
      increasing the effectiveness of police work.

PMID- 10908141
TI  - Economic evaluation of traffic safety measures for transport companies.
AB  - This paper addresses the economic feasibility of measures to reduce the material
      damage of transport companies. Results are presented of a series of interviews
      among transport companies as well as from a postal questionnaire survey. Next,
      calculations are presented for three types of companies: a small family company,
      a large family company and a large formalised company. From the viewpoint of
      costs and benefits, damage prevention measures appear to be particularly
      interesting to larger companies. Small companies, being the largest group, tend
      to have an informal culture in which measures are less effective. Especially
      those measures for which no large investments are needed, which influence the
      behaviour of drivers and need not to be contracted out, are perceived as
      attractive by the transport companies.

PMID- 10908142
TI  - Drink driving as a social problem: comparing the attitudes and knowledge of drink
      driving offenders and the general community.
AB  - Using data from a community survey together with data from a survey of drink
      driving offenders, this paper compares the attitudes and knowledge of two matched
      samples on a number of drink driving issues. The total sample (149 offenders and
      149 community sample respondents) were interviewed using a survey instrument
      containing a number of comparable questions. The offender sample were interviewed
      by trained interviewers in a face-to-face format, while the general community
      sample were interviewed using a computer aided telephone interview system. The
      specific issues dealt with include: a) knowledge of safe drinking and blood
      alcohol consumption (BAC) levels; b) attitudes towards strategies for avoiding
      drink driving; and c) general attitudes regarding drink driving. The analysis
      uses logistic regression to investigate the differences between the responses
      given by the two samples. The findings illustrate a number of significant
      differences in knowledge and attitudes between offenders and the general
      community.

PMID- 10908143
TI  - Monitoring performance of road safety programmes in New Zealand.
AB  - While the number of crashes during a certain time period such as a week, month or
      a year indicates the level of risk on the road, it may fluctuate without any
      change in the actual underlying risk. If the number of crashes increases or
      decreases during a period of time, it indicates one of two possibilities: (1) the
      probability of a crash during the period has changed, or (2) the difference is
      due to the stochastic nature of the event, i.e. it is due to a random
      fluctuation. A control chart system is developed in the paper to identify the
      occurrence of actual risk changes or deviation from the expected level and
      likelihood of meeting the target. The paper discusses the development of control
      charts to monitor fatalities at the national level, which can also be used at
      regional levels, with respect to the pre-set targets. In a traditional control
      chart, the production process is composed of identifiable and controllable
      inputs. The levels of the inputs can be designed before production. In the case
      of road safety, it is not feasible to do so. Here the nature and quality of the
      input 'controls' are such that they may influence the safety outcomes indirectly.
      Estimates of variability used in the analysis must take account of this
      peculiarity. The attainability of a target, to be achieved within a given period,
      depends not only on future safety outcomes but also on outcomes in the past. A
      cumulative control chart has been developed in this paper to particularly
      facilitate the monitoring of targets.

PMID- 10908144
TI  - Risk factors in highway traffic accidents: a case control study.
AB  - The objective of this study was to identify risk factors related to the driver,
      the vehicle and the environment, that are associated with motor vehicles
      accidents on highways. A case and control design was used where the case was: the
      driver of a motor vehicle who was involved in an accident while traveling on the
      Mexico-Cuernavaca highway; and the control was: the driver or a motor vehicle
      who, traveling on the highway, completed the trip without being involved in a
      traffic accident. Risk factors associated with the occurrence of a traffic
      accident (P > 0.05) were: age under 25 years, frequent travel, traveling to work,
      alcohol consumption, driving during the daylight, on a week-day, under adverse
      weather conditions and in the Mexico Cuernavaca direction of road. Risks adjusted
      by logistic regression were: age under 25 years odds ratio (OR) 3.01, confidence
      interval (CI) (95%) 1.46-6.18; work as a travel reason OR 1.74, CI 1.06 2.86;
      alcohol intake OR 4.70, Cl 1.62 13.6; driving under adverse weather conditions OR
      5.70, CI 3.66-8.85; traveling on a week-day OR 1.84, CI 1.14-2.94; during
      daylight hours OR 4.23, CI 2.36-7.58 and in the Mexico Cuernavaca direction of
      road OR 2.69, CI 1.67 4.32. The identification of factors associated with the
      risk of being involved in a highway traffic accident allows us to propose primary
      prevention measures for this important public health problem.

PMID- 10908146
TI  - Evidence of the participation of peribiliary mast cells in regulation of the
      peribiliary vascular plexus along the intrahepatic biliary tree.
AB  - Our pilot study disclosed that tryptase-positive mast cells (MC) were densely
      distributed around the intrahepatic bile ducts (peribiliary MC). In this study,
      the pathophysiologic roles of these MC were examined with respect to the
      microcirculation around the bile duct in 71 cases of histologically normal liver,
      24 cases of chronic hepatitis, and 45 cases of liver cirrhosis. The tryptase
      positive MC were very close to the microvessels of the peribiliary vascular
      plexus (PVP), which supply the intrahepatic biliary tree. The tryptase-positive
      MC were frequently found adjacent to vascular smooth muscle cells, including
      pericytes. The location of the tryptase-positive MC was confirmed by
      ultrastructural analysis. In cirrhosis, the numbers of both microvessels of PVP
      and peribiliary MC increased in parallel. Peribiliary MC were immunoreactive for
      endothelin 1 (ET-1), and were variably immunoreactive for histamine, chymase,
      inducible nitric oxide synthase (iNOS), and endothelin A and B (ET(A) and ET(B))
      receptors, particularly in cirrhotic livers. On vascular endothelial cells of
      PVP, endothelial nitric oxide synthase (eNOS) and ET-1 were consistently
      detectable, and ET(A) receptors, ET(B) receptors, and iNOS were variably
      detectable. Pericytes of PVP expressed ET(A) and ET(B) receptors in addition to
      ET-1 and iNOS. Biliary epithelial cells also focally expressed iNOS, ET-1, and
      ET(A) and ET(B) receptors. These vasoactive substances were strongly expressed on
      the cellular components in cirrhotic liver. By in situ hybridization, iNOS mRNA
      signals were observed on iNOS-immunoreactive cell components, including
      peribiliary MC. These morphologic and immunohistochemical findings suggest that
      the cellular components displaying vasoactive substances in the milieu of the
      intrahepatic biliary tree are very dynamic in the vasoregulation of PVP in normal
      livers, even more so in cirrhosis, and that peribiliary MC exert local effects on
      the microcirculation of PVP, directly and indirectly.

PMID- 10908145
TI  - Epithelial defect in prostates of Stat5a-null mice.
AB  - The transcription factor Stat5a critically mediates prolactin (PRL)-induced
      mammary gland development and lactogenesis. PRL also stimulates growth and
      differentiation of prostate tissue. Specifically, hyperprolactinemia gives rise
      to prostate hyperplasia, and prostate size is reduced in PRL-deficient mice. We
      therefore investigated the importance of Stat5a for prostate development and
      function by examining Stat5a-null mice. The absence of Stat5a in mice was
      associated with a distinct prostate morphology characterized by an increased
      prevalence of local disorganization within acinar epithelium of ventral
      prostates. Affected acini were typically filled with desquamated, granular
      epithelial cells that had become embedded in dense, coagulated secretory
      material. These features were reminiscent of acinar cyst formation and
      degeneration frequently observed in human benign prostate hyperplasia, however,
      cystic changes in prostate acini of Stat5a-deficient mice were not associated
      with increased prostate size or morphologic hallmarks of epithelial hyperplasia.
      Instead, immunohistochemistry of the prostate-specific secretory marker,
      probasin, suggested that hypersecretory function of the epithelium could underlie
      local congestion and cyst formation in prostates of Stat5a-null mice. Serum
      testosterone and PRL levels were normal in Stat5a knockout mice, but prostate PRL
      receptor expression was reduced as determined by immunohistochemistry. Expression
      levels or activation states of other PRL signal transduction proteins, including
      Stat5b, Stat3, Stat1, ERK1, and ERK2 were not altered. The present study offers
      the first evidence for a direct role of Stat5a in the maintenance of normal
      tissue architecture and function of the mouse prostate.

PMID- 10908147
TI  - Statistical analysis of mitochondrial pathologies in childhood: identification of
      deficiencies using principal component analysis.
AB  - Mitochondrial pathologies are a heterogeneous group of metabolic disorders that
      are frequently characterized by anomalies of oxidative phosphorylation,
      especially in the respiratory chain. The identification of these anomalies may
      involve many investigations, and biochemistry is a main tool. However,
      considering the whole set of biochemical data, the interpretation of the results
      by the traditionally used statistical methods remains complex and does not always
      lead to an unequivocal conclusion about the presence or absence of a respiratory
      chain defect. This arises from three main problems: (a) the absence of an a
      priori-defined control population, because the determination of the control
      values are derived from the whole set of investigated patients, (b) the small
      size of the population studied, (c) the large number of variables collected, each
      of which creates a wide variability. To cope with these problems, the principal
      component analysis (PCA) has been applied to the biochemical data obtained from
      35 muscle biopsies of children suspected of having a mitochondrial disease. This
      analysis makes it possible for each respiratory chain complex to distinguish
      between different subsets within the whole population (normal, deficient, and, in
      between, borderline subgroups of patients) and to detect the most discriminating
      variables. PCA of the data of all complexes together showed that mitochondrial
      diseases in this population were mainly caused by multiple deficits in
      respiratory chain complexes. This analysis allows the definition of a new
      subgroup of newborns, which have high respiratory chain complex activity values.
      Our results show that the PCA method, which simultaneously takes into account all
      of the concerned variables, allows the separation of patients into subgroups,
      which may help clinicians make their diagnoses.

PMID- 10908148
TI  - Analysis of chromosomal alterations in non-small cell lung cancer by multiplex
      FISH, comparative genomic hybridization, and multicolor bar coding.
AB  - Lung cancer has a considerable impact on morbidity and mortality throughout the
      world. Despite extensive effort, no lung cancer-specific cytogenetic changes,
      such as lineage-specific translocations or inversions, have been described to
      date. In this study we used multiplex fluorescence in situ hybridization (M
      FISH), comparative genomic hybridization, and multicolor bar coding to analyze
      eight cell lines derived from non-small cell lung cancers. M-FISH did not
      identify any balanced translocations, which are the dominating feature in
      leukemias and lymphomas. Instead, M-FISH unraveled an enormous number of
      numerical and structural aberrations, with each tumor having its own "private"
      pattern of chromosomal changes. In contrast, comparative genomic hybridization
      demonstrated similarities between tumors, because each cell line shared some
      chromosomal segments that were commonly gained or lost. One of these involved
      chromosome 12. Chromosome 12 specific bar code probe sets were constructed and
      used to demonstrate that breaks on chromosome 12 occur preferentially within
      specific bands. With the progressive use of higher resolution approaches, more
      information can be gained about the chromosomal alterations in cancer.

PMID- 10908149
TI  - Localization of Borrelia burgdorferi in the nervous system and other organs in a
      nonhuman primate model of lyme disease.
AB  - Lyme borreliosis is caused by infection with the spirochete Borrelia burgdorferi.
      Nonhuman primates inoculated with the N40 strain of B. burgdorferi develop
      infection of multiple tissues, including the central (CNS) and peripheral nervous
      system. In immunocompetent nonhuman primates, spirochetes are present in low
      numbers in tissues. For this reason, it has been difficult to study their
      localization and changes in expression of surface proteins. To further
      investigate this, we inoculated four immunosuppressed adult Macaca mulatta with 1
      million spirochetes of the N40 strain of B. burgdorferi, and compared them with
      three infected immunocompetent animals and two uninfected controls. The brain,
      spinal cord, peripheral nerves, skeletal muscle, heart, and bladder were obtained
      at necropsy 4 months later. The spirochetal tissue load was first studied by
      polymerase chain reaction (PCR)-ELISA of the outer surface protein A (ospA) gene.
      Immunohistochemistry was used to study the localization and numbers of
      spirochetes in tissues and the expression of spirochetal proteins and to
      characterize the inflammatory response. Hematoxylin and eosin and trichrome
      stains were used to study inflammation and tissue injury. The results showed that
      the number of spirochetes was significantly higher in immunosuppressed animals.
      B. burgdorferi in the CNS localized to the leptomeninges, nerve roots, and dorsal
      root ganglia, but not to the parenchyma. Outside of the CNS, B. burgdorferi
      localized to endoneurium and to connective tissues of peripheral nerves, skeletal
      muscle, heart, aorta, and bladder. Although ospA, ospB, ospC, and flagellin were
      present at the time of inoculation, only flagellin was expressed by spirochetes
      in tissues 4 months later. Significant inflammation occurred only in the heart,
      and only immunosuppressed animals had cardiac fiber degeneration and necrosis.
      Plasma cells were abundant in inflammatory foci of steroid-treated animals. We
      concluded that B. burgdorferi has a tropism for the meninges in the CNS and for
      connective tissues elsewhere in the body.

PMID- 10908150
TI  - Comparative genomic and in situ hybridization of germ cell tumors of the
      infantile testis.
AB  - Chromosomal information on germ cell tumors of the infantile testis, ie,
      teratomas and yolk sac tumors, is limited and controversial. We studied two
      teratomas and four yolk sac tumors using comparative genomic hybridization (CGH)
      and in situ hybridization. No chromosomal anomalies were found in the teratomas
      by any of the methods, not even after CGH on microdissected tumor cells. All yolk
      sac tumors showed aneuploidy, loss of parts of 4q and 6q, and gain of parts of
      20q. Underrepresentation of parts of 8q and overrepresentation of parts of 3p,
      9q, 12p, 17, 19q, and 22 were detected in most cases. In addition, one recurrent
      yolk sac tumor after a sacral teratoma was studied, showing a highly similar
      pattern of imbalances. While CGH demonstrated loss of 1p36 in one testicular yolk
      sac tumor, in situ hybridization revealed loss of this region in all yolk sac
      tumors. High-level amplification of the 12q13-q14 region was found in one yolk
      sac tumor. MDM2, of which the encoding gene maps to this chromosomal region, was
      found in all cases using immunohistochemistry, whereas no p53 could be detected.
      Accordingly, no mutations within exons 5 to 8 of the p53 gene were observed.
      These data prove the absence of gross chromosomal aberrations in teratomas of the
      infantile testis and show a characteristic pattern of gains and losses in the
      yolk sac tumors. Besides confirmation of previously found anomalies, recurrent
      losses of 1p21-31 and 4q23-33 and gains of 9q34 and 12p12-13 have not been
      reported before. While genetic inactivation of p53 seems unimportant in the
      pathogenesis of these tumors, biochemical inactivation by MDM2 might be involved.
      These data support the existence of three entities of germ cell tumors of the
      human testis: teratomas and yolk sac tumors of infants, seminomas and
      nonseminomas of adolescents and young adults, and spermatocytic seminomas of the
      elderly, each with its own specific pathogenesis.

PMID- 10908151
TI  - Discriminative immunophenotype of bronchoalveolar lavage CD4 lymphocytes in
      sarcoidosis.
AB  - The diagnosis of pulmonary sarcoidosis relies in part on the observation of
      alveolar CD4+ lymphocytosis. However, this criterion is not fully discriminative
      because this anomaly is also found in other types of lung diseases. Among other
      possible distinctive criteria, we investigated the expression of lymphocyte
      addressing molecules, which could differ according to the pathophysiology of lung
      diseases. We investigated CD103 (alpha(E)beta7 integrin, CD103-beta7), reported
      to be both expressed on intra-epithelial lymphocytes in mucosal areas, including
      bronchi, and possibly involved in the recruitment of alveolar lymphocytes. The
      expression of CD103 was examined on bronchoalveolar lavage lymphocytes from 93
      consecutive patients, including 34 patients with CD4+ lymphocytosis. For all
      patients, the expression of CD19, CD3, CD4, CD8, CD57, LFA1, DR, and CD103 was
      assessed by flow cytometry. Sarcoidosis seemed remarkably characterized by the
      lack of CD103 expression on the predominant CD4+ subset. Statistically
      significant differences were found between patients with sarcoidosis, with other
      types of CD4+ lymphocytosis, and with other lung disorders in the CD103+ cell
      levels and in the CD103/CD4 ratio. Combined use of the CD4/CD8 ratio (> 2.5) and
      the CD103/CD4 ratio (< 0.31) to assess bronchoalveolar lavage lymphocytes is a
      promising new tool for the diagnosis of sarcoidosis.

PMID- 10908152
TI  - Mammaglobin gene expression: a superior marker of breast cancer cells in
      peripheral blood in comparison to epidermal-growth-factor receptor and
      cytokeratin-19.
AB  - Various molecular markers have been used for the detection of circulating breast
      cancer cells in blood by reverse transcriptase-polymerase chain reaction (RT
      PCR). Using nested RT-PCR, we compared the specificity and sensitivity of human
      mammaglobin (hMAM), epidermal-growth-factor receptor (EGF-R), and cytokeratin 19
      (CK-19) expression as markers for circulating carcinoma cells in the peripheral
      blood of patients with breast cancer. Blood samples from 12 patients with ductal
      carcinoma in situ, 133 patients with invasive breast cancer, 20 patients with
      hematological malignancies, 31 healthy volunteers, and tumor tissues from 40
      patients with invasive breast cancer were screened for mRNA encoding hMAM, EGF-R,
      or CK-19 by nested RT-PCR. In all breast cancer tissues, mRNA for hMAM, EGF-R,
      and CK-19 was detectable. In blood samples from patients with invasive breast
      cancer, 11 (8%), 13 (10%), and 64 (48%) were positive for mRNA encoding hMAM, EGF
      R, or CK-19, respectively. Blood samples from none of the healthy volunteers and
      patients with hematological disorders were positive for hMAM, while CK-19 mRNA
      was found in the blood of 12 (39%) healthy volunteers and transcripts for EGF-R
      and CK-19 were detectable in 5 (25%) and 2 (10%), respectively, of the patients
      with hematological malignancies. Only hMAM mRNA expression in blood correlated
      with clinical parameters such as nodal status, metastasis, and CA 15-3 serum
      levels. In summary, hMAM transcripts detectable in blood by RT-PCR represent the
      most specific molecular marker for hematogenous spread of breast cancer cells.
      With the nested RT-PCR method, aberrant EGF-R mRNA expression might occasionally
      be found in hematological malignancies, whereas CK-19 mRNA expression proved to
      be rather nonspecific. The prognostic value of hMAM RT-PCR-based tumor cell
      detection in peripheral blood should be further tested and validated in
      prospective studies.

PMID- 10908154
TI  - High density deletion mapping of bladder cancer localizes the putative tumor
      suppressor gene between loci D8S504 and D8S264 at chromosome 8p23.3.
AB  - Deletion of chromosome 8p is associated with the progression of bladder cancer.
      To identify the putative tumor suppressor gene locus we have analyzed 145 bladder
      cancers with 12 microsatellite markers for allelic changes at the chromosome
      8p23.3 region. We mapped the smallest overlapping deletion to approximately 0.7
      cM genetic distance between loci D8S504 and D8S264. Allelic changes at this
      region occurred in 75 (52%) of the 145 tumors. We found a significant correlation
      between alterations at chromosome 8p23.3 and the tumor grade. The correlation
      between genetic changes and tumor stage reflected the distribution of tumors of
      different grades in each pathologic stage.

PMID- 10908153
TI  - Down-regulation of renal endothelial nitric oxide synthase expression in
      experimental glomerular thrombotic microangiopathy.
AB  - Infection with certain strains of Escherichia coli and endotoxemia results in
      renal glomerular thrombotic microangiopathy (TMA) characterized by endothelial
      swelling and prominent glomerular microthrombus formation. Nitric oxide (NO) is
      an endogenous biologic modulator with diverse physiologic functions including
      vasodilation and inhibition of platelet adhesion and aggregation. NO is
      synthesized from conversion of L-arginine to L-citrulline by a family of NO
      synthases (NOS), which include constitutive and inducible isoforms. Indirect
      evidence supports the hypothesis that TMA is associated with depressed intrarenal
      NO production. However, the effect of TMA on renal tissue NOS expression has not
      been fully elucidated. We studied rats with TMA induced by iv bolus injection of
      high dose (20 mg/kg) E. coli endotoxin. Subgroups of six animals each were
      sacrificed before or at 30, 90, 180, 360, and 720 minutes after the
      administration of endotoxin. Renal histology and tissue expression of endothelial
      and inducible nitric oxide synthases (eNOS and iNOS) were examined. Additionally,
      we examined the effect of endotoxin on glomerular NO production, and eNOS and
      iNOS protein expression in vitro. Glomerular capillary thrombosis developed by
      180 minutes after endotoxin administration in approximately half of the animals.
      The glomeruli without thrombotic lesions apparent by light microscopy disclosed
      early signs of TMA characterized by endothelial swelling, platelet
      accumulation/adhesion, and patchy fibrinogen deposition. These morphologic
      changes were associated with a marked reduction of renal tissue eNOS expression
      beyond 180 minutes after the endotoxin administration. The fall in eNOS
      expression was coupled with a significant rise in iNOS protein abundance, which
      was expressed largely by glomerular circulating neutrophils and endothelial
      cells, peritubular vascular endothelium, and collecting ducts of cortex and
      medulla. In vitro incubation of isolated glomeruli with endotoxin also resulted
      in a marked reduction in eNOS expression and a significant rise in iNOS content.
      Administration of E. coli endotoxin leads to a sustained fall in renal eNOS
      expression both in vivo and in vitro. The associated decline in intrarenal
      endothelial NO production/availability may result in renal vasoconstriction and a
      hypercoagulative state, which may contribute to the pathogenesis of endotoxin
      induced TMA.

PMID- 10908155
TI  - Inhibition of monocyte chemotactic protein-1 synthesis by statins.
AB  - The beneficial effects of statins on the reduction of cardiovascular events has
      been partly attributed to their anti-inflammatory properties. In the complex of
      the different pathogenetic events leading to atherosclerosis, recent data suggest
      a central role of monocyte chemotactic protein-1 (MCP-1), because mice knock-out
      for MCP-1 or its receptor CC-chemokine receptor 2 were considerably resistant to
      plaque formation. In this study we investigated the effect of different statins
      on in vitro and in vivo production of MCP-1. Lovastatin and simvastatin caused a
      dose-dependent inhibition of MCP-1 production in peripheral blood mononuclear
      cells exposed to lipopolysaccharide or inactivated Streptococcus hemoliticus and
      in human endothelial cells exposed to interleukin-1beta. The addition of
      mevalonate overrode the inhibitory effect of statins indicating that mevalonate
      derived products are important for chemokine production. The in vivo anti
      inflammatory effect of statins was investigated using the mouse air-pouch model
      of local inflammation. Lovastatin and pravastatin were orally administered to
      mice according to a treatment schedule that significantly inhibited the hepatic 3
      hydroxy-3-methylglutaryl coenzyme A reductase activity without affecting total
      blood cholesterol. At the dose of 10 mg/kg, lovastatin and pravastatin reduced by
      approximately 50% the lipopolysaccharide-induced leukocytes recruitment and the
      exudate MCP-1 production. In conclusion, statins, by inhibiting mevalonate
      derived products, reduced both in vitro and in vivo the production of chemokines
      involved in leukocyte migration, and this effect is unrelated to their
      cholesterol-lowering action.

PMID- 10908156
TI  - Interaction of the receptor for advanced glycation end products (RAGE) with
      transthyretin triggers nuclear transcription factor kB (NF-kB) activation.
AB  - Mutated transthyretin (TTR) fibrils are associated with the pathology of familial
      amyloidotic polyneuropathy (FAP), in which extracellular amyloid deposits lead to
      degeneration of cells and tissues, in particular neurons of the peripheral nerve.
      Here we present evidence that the receptor for advanced glycation end products
      (RAGE), previously associated with Alzheimer's disease, acts as a selective cell
      surface acceptor site for both soluble and fibrillar TTR. Immunohistochemical
      studies demonstrating increased expression of RAGE in FAP tissues suggested the
      relevance of this receptor to TTR-induced fibrillar pathology. In vitro studies
      using soluble RAGE showed saturable specific interaction with soluble and
      fibrillar TTR with a K(d) of approximately 120 nM. However, no binding was
      observed when soluble TTR was combined with retinol-binding protein, which
      represents the form in which TTR normally circulates in plasma. Specific binding
      of TTR to RAGE-transfected Chinese hamster ovary cells (which was completely
      blocked by anti-RAGE) was observed, confirming that RAGE could mediate TTR
      binding to cellular surfaces. RAGE-dependent activation of nuclear transcription
      factor kB (NF-kB) by TTR fibrils was shown in PC-12 cells stably transfected to
      overexpress the receptor. Furthermore, FAP nerves showed up-regulation of p50,
      one of the NF-kB subunits, when compared with age-matched controls. From these
      observations we predict that, in vivo, the presence of TTR fibrils associated
      with cellular surfaces of FAP patients, by contributing to NF-kB activation,
      leads to the pathogenesis of neurodegeneration. Further insights into the
      consequences of the interaction of fibrillar TTR with RAGE may therefore provide
      a better understanding of neurodegeneration associated with FAP.

PMID- 10908157
TI  - Autocrine growth regulation of CD30 ligand in CD30-expressing Reed-Sternberg
      cells: distinction between Hodgkin's disease and anaplastic large cell lymphoma.
AB  - Persistent expression of high levels of CD30 in Hodgkin's Reed-Sternberg (H-RS)
      cells and anaplastic large-cell lymphoma (ALCL) cells, but not in most T- or B
      cell lymphomas, suggests the presence of an underlying mechanism leading to the
      abnormality and possible involvement of CD30 in the growth and survival of these
      two unique types of tumors. In this study, we examined the effect of CD30 ligand
      (CD30L) on CD30-positive H-RS and ALCL cells in long-term cultures or in primary
      cultures. CD30L induced various degrees of proliferation in three long-term
      cultured H-RS cell lines (L428, HDLM-2, and KM-H2) as well as in primary cultures
      of H-RS cells obtained directly from patients with Hodgkin's disease. In
      contrast, significant inhibition was observed in one of the ALCL cell lines (SU
      DHL-1), but no growth inhibition or promotion in responding to exogenous CD30L
      was detected in three others (PB-1, JB-6, and McG-2), nor in primary cultures of
      ALCL cells. Expression of CD30L was determined by polymerase chain reaction in
      long-term cultured cells and by an immunohistochemical method in H-RS or ALCL
      cells de novo in tissue sections. None of the H-RS and ALCL cell lines was
      positive for CD30L. In tissue sections, we noticed that ALCL cells were generally
      CD30L-negative. In contrast, the anti-CD30L antibody reacted with a majority of H
      RS cells with diffuse cytoplasmic staining. Most H-RS cells were CD30-positive,
      indicating co-expression of CD30 and CD30L in the majority of lymphoma cells. The
      persistent high levels of CD30 and CD30L expression in H-RS cells suggest that
      the autocrine CD30L-CD30 cytokine-receptor loop, in addition to having the
      paracrine activity previously thought to exist, could play important roles in the
      proliferation of H-RS cells. In contrast, the CD30L-mediated cytotoxicity may
      participate in the regression or slow progression of ALCL during the early phase
      of the disease in selected patients. However, when the disease progresses, the
      ALCL cells are likely to become resistant to exogenous CD30L.

PMID- 10908158
TI  - Presence of human herpesvirus-8 DNA sequences and overexpression of human IL-6
      and cyclin D1 in inflammatory myofibroblastic tumor (inflammatory pseudotumor).
AB  - Inflammatory myofibroblastic tumor (IMT) is composed of myofibroblasts, plasma
      cells, and lymphocytes. Cytokines are possibly involved in its pathogenesis.
      Human herpesvirus-8 (HHV-8) encodes cell cycle regulatory and signaling proteins.
      A combination of nested PCR with several negative controls and Southern blot
      methods showed the presence of HHV-8 DNA in seven cases of IMT. Additionally,
      strong expression was demonstrated by in situ hybridization in many tumoral
      nuclei. Most of the myofibroblasts in all of the cases were immunoreactive for
      human IL-6 and cyclin D1. These cytokines probably have a paracrine action and
      may sustain myofibroblastic growth. HHV-8 could play an essential role in
      triggering IMT development by a local reactivation of viral lytic replication.
      The relationship between HHV-8 and immunosuppression status as the only
      associated cause for tumorigenesis should be revised.

PMID- 10908159
TI  - Roles and relationship of macrophages and monocyte chemotactic and activating
      factor/monocyte chemoattractant protein-1 in the ischemic and reperfused rat
      heart.
AB  - Reperfusion injury is a troublesome and unresolved problem in acute myocardial
      infarction and is believed to be associated with inflammatory reactions in which
      various types of cells and cytokines participate, in particular, macrophages and
      monocyte chemoattractant protein-1 (MCP-1). We designed this study to clarify the
      role and relationship of macrophages and MCP-1 in ischemic and reperfused heart.
      The number and distribution of macrophages and MCP-1 messenger RNA (mRNA) in the
      ischemic and reperfused rat heart were examined with in situ hybridization and
      immunohistochemistry. Myocardial samples were obtained at several times. In situ
      hybridization was performed with digoxigenin-labeled antisense RNA probe for rat
      MCP-1 mRNA, and immunohistochemistry was performed with antimacrophage antibody.
      Double staining with in situ hybridization and immunohistochemistry was also
      performed. The number of MCP-1 mRNA-positive cells increased after reperfusion
      and peaked at 3 hours after reperfusion. Early infiltration of ischemic tissues
      by macrophages was also observed at the time of the absence of an increase of MCP
      1 mRNA-positive cells, and this infiltration was not significantly accelerated by
      reperfusion, but by ischemia itself. The numbers of both MCP-1 mRNA-positive
      cells and macrophages increased in the ischemic marginal region over time. From
      the result of double staining, and based on the cellular morphology and the
      distribution, the majority of MCP-1 mRNA-positive cells appeared to be activated
      macrophages. This suggests that macrophages may not be attracted to cardiac
      tissue only by MCP-1 and that MCP-1 may have some roles other than attracting
      macrophages into ischemic heart. It also suggests that macrophages and MCP-1 may
      play an important role in reperfusion injury and that MCP-1 may be one of the key
      molecules of reperfusion injury. These observations may contribute to the
      development of a new therapeutic approach to the prevention of reperfusion
      injury.

PMID- 10908160
TI  - Hepatitis C virus from the hearts of patients with myocarditis and
      cardiomyopathy.
AB  - The myocardium may be the target of several types of viral infections. The
      importance of hepatitis C virus (HCV) infection has been recently noted in
      patients with myocarditis and in patients with dilated or hypertrophic
      cardiomyopathy. The present study sought to detect HCV genomes in formalin-fixed
      paraffin sections of autopsied hearts from patients with myocarditis and patients
      with dilated or hypertrophic cardiomyopathy. Paraffin sections were
      deparaffinized, RNA was extracted, and the positive and negative strands of HCV
      RNA were detected by performing reverse transcription and nested polymerase chain
      reaction. The polymerase chain reaction products were cloned and sequenced. beta
      actin gene was used as a control for the successful amplification of a
      housekeeping gene. Among 106 hearts examined, beta-actin gene was amplified in 61
      hearts (57.5%). Among the latter, HCV RNA was detected in 13 hearts (21.3%), and
      negative strands in 4 hearts (6.6%). HCV RNA was found in 4 hearts (33.3%) with
      myocarditis, in 3 hearts (11.5%) with dilated cardiomyopathy, and in 6 hearts
      (26.0%) with hypertrophic cardiomyopathy. The sequences recovered from nine
      patients were highly homologous to the standard strain of HCV. HCV genomes were
      not found in either 35 hearts from patients with myocardial infarction or 20
      hearts from patients with noncardiac diseases. These HCV RNA positive samples
      were obtained from 1 heart in 1979, 7 hearts between 1980 and 1989, and 5 hearts
      since 1990, indicating that HCV RNA can be amplified from paraffin-embedded
      hearts preserved for many years. This method of detecting HCV genomes in formalin
      fixed paraffin cardiac specimens has enabled us to widen our research into HCV
      infection and has been helpful in identifying the presence of HCV infection in
      cardiac myopathic disorders.

PMID- 10908161
TI  - Leptin levels in relation to body composition and insulin concentration in
      patients with endogenous Cushing's syndrome compared to controls matched for body
      mass index.
AB  - Cushing's syndrome (CS) is associated with weight gain and visceral obesity. We
      examined the relationship between regional fat distribution and serum levels of
      leptin, cortisol and insulin. Twenty-three consecutive patients with recently
      diagnosed CS (18 with pituitary adenoma, 5 with adrenal tumor), where compared to
      obese controls, matched for age, sex and Body Mass Index (BMI). Serum insulin,
      leptin, cortisol, C-peptide and body composition determined by DEXA were
      measured. Serum leptin levels were significantly increased in patients with CS
      (36.9+/-3.8 vs 18.9+/-2.4 ng/ml, p<0.001; women: 40.1+/-4.6 vs 21.7+/-2.9 ng/ml,
      p<0.01; men: 27.9+/-5.7 vs 10.9+/-2.3 ng/ml; p<0.05), the same were fasting
      insulin levels (178+/-30 vs 81+/-10 pmol/l; p<0.01) and C-peptide (1.51+/-0.12 vs
      0.77+/-0.07 nmol/l; p<0.001). In a subgroup of 12 patients, truncal fat mass was
      significantly elevated when compared to obese controls (19.2 kg vs 14.7 kg,
      p<0.01, and 42% vs 36% in percentage of truncal body tissue, p<0.05), whereas
      total fat mass was insignificantly increased. Serum leptin correlated positively
      to total body fat (%) as in patients with CS (r=0.94, p<0.001) as in controls
      (r=0.68, p<0.01). The correlation to truncal body fat (%) was also significant in
      both groups (CS: r=0.84, p<0.001; controls: r=0.63, p<0.01). Multiple regression
      showed that percent total body fat was the predictor of leptin concentrations
      among patients with CS (r2=0.88, p<0.001) whereas insulin did not contribute
      significantly to the variance in leptin concentrations. In controls, both leptin
      and insulin (r2=0.65, p<0.001) contributed significantly to the variations in
      leptin levels. Controlled for the differences in total body fat, patients with
      endogenous CS have significantly increased serum leptin levels, compared to BMI
      matched obese controls. This suggests that hyperleptinemia in CS not primarily
      reflects changes in body composition, but is the result of different hormonal
      influences on adipose tissue.

PMID- 10908162
TI  - Effects of 12 months rec-GH therapy on bone and collagen turnover and bone
      mineral density in GH deficient children with thalassaemia major.
AB  - Children suffering from thalassaemia major are reported to have growth delay and
      bone alterations even when well transfused and chelated. In the present study we
      evaluated bone and collagen turnover (bone Gla-protein, BGP; carboxyterminal
      telopeptide of type I collagen, ICTP; aminoterminal propeptide of type III
      procollagen, PIIINP, respectively) and bone mineral density (BMD) in 5 pre
      pubertal GH deficient thalassaemic children before and during rec-GH treatment
      (0.6 IU/kg/week). Data were compared with those recorded in an age- and sex
      matched control group. Before treatment, serum BGP and ICTP levels were
      significantly lower (p<0.0001) in children with thalassaemia (9.3+/-0.7 ng/ml and
      5.3+/-0.5 ng/ml, respectively) than in healthy controls (18.9+/-0.9 ng/ml and
      14.4+/-0.6 ng/ml, respectively), while serum PIIINP levels did not significantly
      differ in the two groups (6.7+/-0.7 ng/ml vs 6.7+/-0.7 ng/ml). Mean lumbar BMD
      values of patients (0.62+/-0.05 g/cm2) were significantly lower (p<0.05) than
      those recorded in healthy controls (0.78+/-0.01 g/cm2), while femoral BMD values
      were similar in the two groups (patients: 0.70+/-0.08 g/cm2 vs controls: 0.74+/
      0.01 g/cm2). One-year GH therapy significantly increased height velocity (from
      2.3+/-0.2 cm/year to 6.1+/-0.4 cm/yr, p<0.0001) and IGF-I levels (from 61.6+/
      15.4 to 342+/-38.5 ng/ml, p<0.005). Serum BGP (basal: 9.3+/-0.7 ng/ml, 6th month:
      10.8+/-0.6 ng/ml, 12th month: 14.9+/-1.4 ng/ml), ICTP (basal: 5.3+/-0.5 ng/ml,
      6th month: 7.9+/-0.8 ng/ml, 12th month: 10.9+/-1.7 ng/ml) and PIIINP levels
      (basal: 6.7+/-0.7 ng/ml, 6th month: 9.9+/-1.0 ng/ml, 12th month: 9.6+/-1.4 ng/ml)
      significantly increased (p<0.05), while no significant effects were observed on
      lumbar and femoral BMD values. Although the GH-induced stimulation of bone
      turnover markedly increased BGP (+60%) and ICTP (+105%) levels, one-year GH
      therapy was not sufficient to completely normalize these parameters, which
      remained significantly lower than in healthy controls. In conclusion, our study
      shows that pre-pubertal GH deficient children with thalassaemia major have
      reduced bone turnover (both bone formation and resorption) and lumbar BMD values,
      thus indicating that bone metabolism should be monitored and improved even in
      well-transfused patients. One-year GH treatment is able to increase, but not
      normalize, bone turnover, this effect being insufficient to improve BMD values.
      More prolonged periods of GH therapy are probably requested to positively affect
      both bone turnover and BMD values in GH deficient thalassaemic patients, as
      occurs in children and adults with GH deficiency.

PMID- 10908163
TI  - Serum androgen levels in adolescents with type 1 diabetes: relationship to
      pubertal stage and metabolic control.
AB  - Delayed sexual maturation is still frequently seen in adolescents with type 1
      diabetes. A close relationship between insulin and androgen metabolism has been
      found in a number of studies. Our study was designed to investigate whether or
      not abnormalities in androgen secretion could play a role in the onset of sexual
      maturation in adolescents with type 1 diabetes. We have asked whether or not
      there was a correlation between daily insulin dosage, duration of diabetes,
      metabolic control, age, pubertal stage, and body mass index (BMI) versus serum
      androgen concentrations. Basal total and free testosterone,
      dehydroepiandrosterone-sulfate (DHEA-S), dihydrotestosterone (DHT), sex hormone
      binding globulin (SHBG) and 3alpha-androstanediol glucuronide (3alpha diol-G)
      plasma concentrations were measured in 36 pubertal boys and 31 pubertal girls
      with type 1 diabetes and in 59 sex- and pubertal stage-matched control subjects
      without diabetes. Significantly higher serum total testosterone (p<0.01) and free
      testosterone (p<0.05) levels were found in females and males with type 1 diabetes
      than in controls at pubertal stage 5. DHEA-S, SHBG, DHT and 3alpha diol G
      concentrations in patients with diabetes were not significantly different from
      those in controls. There was no correlation between daily insulin requirements
      and serum androgen levels. These data suggest that adolescents with diabetes have
      similar serum levels of DHEA-S, SHBG, DHT and 3alpha diol G as healthy subjects
      at all stages of puberty. However, there are significant differences in serum
      testosterone and free testosterone levels in adolescents with diabetes when
      compared to healthy, sex- and pubertal stage-matched controls in late puberty. We
      hypothesize that the increased testosterone levels in patients with diabetes
      could relate to reduced fertility in females, disorders of sexual maturation and
      an increased risk for cardiovascular complications later in life.

PMID- 10908164
TI  - Immunofluorescence distribution of actin-associated proteins in human
      seminiferous tubules of adolescent testes, normal and pathologic.
AB  - The aim of our study on human seminiferous tubules of adolescent testes was to
      study the localization of two actin-associated proteins of the adherens
      junctions, such as vinculin and talin, and to verify if there were modifications
      in their pattern in varicocele, a frequent disease of the testis in adolescent
      age. The study group consisted of 8 biopsies from normal testes (i.e.,
      adolescents operated on for hydrocele or inguinal hernia) and 20 biopsies from
      pathological testes (i.e., adolescents operated on for idiophatic left
      varicocele). Biopsies were evaluated by indirect immunofluorescence using anti
      human vinculin and anti-human talin antibodies. Observation was recorded with a
      Leica TCS 4D upright confocal microscope. In the normal testes, there was a
      strong positive immunoreactivity for vinculin, which was localized in the
      interstitial cells of Leydig, and both basal pole and lateral cell surface of
      Sertoli cells; the pattern of talin immunoreactivity was the same except that the
      lateral cell surface of Sertoli cells was not stained. In the varicocele group
      the pattern was different. Vinculin immunoreactivity showed small patches of
      fluorescence only in the cytoplasm of Sertoli cells while talin immunoreactivity
      showed a scanty distribution at the basal surface of Sertoli cells. These results
      confirm that, similarly to other tissues, vinculin is expressed at cell-cell and
      cell-matrix adherens junctions, while talin is present at cell-matrix adherens
      junctions in human seminiferous tubules of normal adolescents. Varicocele alters
      the patterns of these two proteins both quantitatively and qualitatively.

PMID- 10908165
TI  - Effect of hormone replacement therapy on post-menopausal changes of lymphocytes
      and T cell subsets.
AB  - Immunosenescence is associated with the occurrence of lethal diseases, such as
      infection and malignancy. Since endocrinosenescence occurs simultaneously with
      immunosenescence, we determined whether or not lymphocytes and T cell subsets
      were altered in post-menopausal women. The ability of hormone replacement therapy
      (HRT) to reverse or modify the aberrations of the cell populations observed in
      elderly women was also examined. Thirty-nine untreated post-menopausal women and
      39 women on HRT were studied. The proportions of lymphocytes and T cell subsets
      (helper, cytotoxic and immature T cells, and naive and memory/activated T cells)
      were determined by two color flow cytometry. Thirteen women were examined before
      and during HRT. At late post-menopause (> or = 30 years post-menopausal period),
      the proportion of peripheral blood lymphocytes showed a tendency to decline
      (p=0.06) compared with that at early (< or = 10 years) post-menopause.
      Significant (p<0.05) decrease in naive T cells and an increase in
      memory/activated T cells occurred at late post-menopause compared to those at
      early post-menopause. The percentage of lymphocytes in women on HRT was
      significantly (p<0.05) higher than that in untreated women at late post
      menopausal stage. Furthermore, in a prospective study, HRT induced a significant
      (p<0.02) increase in the percentage of lymphocytes but showed no effect on the
      aberrations of naive and memory/activated T cells. HRT prevents the decline in
      the lymphocytes observed in post-menopausal women. However, HRT appears not to
      influence the observed alteration in T cell subsets.

PMID- 10908166
TI  - Increased levothyroxine requirements presenting as "inappropriate" TSH secretion
      syndrome in a patient with nephrotic syndrome.
AB  - Patients with primary thyroid failure on levothyroxine (LT4) replacement who
      develop nephrotic syndrome (NS) may rarely present with an increase in LT4
      requirements. In this report, we describe a patient with thyroid failure
      following radioactive iodine ablation for Graves' disease who required an
      escalation of LT4 doses following the onset of NS. The case presented with
      disproportionately elevated TSH levels in the presence of normal (or slightly
      subnormal) thyroid hormone levels, thus, masquerading as a state of
      "inappropriate" TSH secretion. This pattern of extreme dysregulation in thyroid
      function indices due to urinary loss of thyroid hormones has not been previously
      described in NS, and, therefore, extends the spectrum of endocrine manifestations
      of NS.

PMID- 10908167
TI  - A giant prolactinoma presenting with unilateral exophthalmos: effect of
      cabergoline and review of the literature.
AB  - We report the case of a 45-year-old male presenting with unilateral exophthalmos
      due to a large tumoral mass invading the skull base. Ophthalmologic examination
      did not show any visual field defects. Imaging techniques demonstrated extension
      of a huge tumor (approx. 8x8x8 cm) into the right orbit and nasopharynx.
      Endocrine work-up revealed grossly elevated serum prolactin (PRL) levels (26,466
      microg/l, nl. < 12), pointing to a large, invasive macroprolactinoma. Stimulation
      tests indicated associated partial adrenal and growth hormone deficiencies.
      Planned surgery was abandoned, and the patient was instead treated with the long
      acting dopamine agonist, cabergoline. Over a period of one year, serum PRL
      dropped to 131 microg/l, while the tumor mass shrank to less than 50% of its
      original volume (with 3.5 mg/week of cabergoline). The exophthalmos disappeared,
      and the patient did not develop rhinorrhea or any other side effects from
      treatment with cabergoline. The efficacy was maintained throughout the second
      year (ultimate serum PRL 74 microg/l, and final size less than 10% of the
      original). With reference to this case, we review other macroprolactinomas
      reported in the recent literature for associated exophthalmos, grossly elevated
      serum PRL levels (> or = 15,000 microg/l), and/or "giant" size (> or = 4 cm in
      maximum diameter). We highlight the use of dopamine agonists in the treatment of
      prolactinomas with such unusual characteristics.

PMID- 10908168
TI  - Occurrence of Riedel's thyroiditis in the course of sub-acute thyroiditis.
AB  - Riedel's Thyroiditis is an uncommon form of chronic thyroiditis characterized by
      an invasive fibrosclerosis of the gland, often involving surrounding tissue. The
      relationship of Riedel's Thyroiditis to other forms of thyroiditis is not clear.
      We presented a 47 year-old woman first diagnosed with sub-acute thyroiditis based
      on clinical findings and laboratory results. Eight months later, she had a
      thyroidectomy operation due to an enlargement of the thyroid gland and symptoms
      of compression. Histopathologic evaluation showed that she had Riedel's
      Thyroiditis, but there were some histopathologic findings of sub-acute
      thyroiditis as well. Until now, there has only been one case reported in which
      Riedel's Thyroiditis was diagnosed in a patient with a history of sub-acute
      thyroiditis in the literature. Although aetiology of Riedel's Thyroiditis is
      unknown, it may develop in the course of sub-acute thyroiditis.

PMID- 10908169
TI  - Myth and reality of the decline in semen quality: an example of the relativity of
      data interpretation.
AB  - Many hypotheses have been put forward to explain a suspected decline in semen
      quality. Up to now many sources of data were used but conflicting results are
      present in the literature. To study whether modifications of sperm parameters
      actually exist we used data from two groups of patients checked and two small
      groups of sperm bank donors selected at the beginning '80s and '90s. We tried to
      reduce bias to a minimum: all the semen analyses were carried out by the same
      biologist, using the same methods, groups were clinically evaluated by the same
      andrological team, the study groups were homogeneous for age, geographic-ethnic
      origin, residence, monthly-seasonal distribution and abstinence period. Comparing
      patients from the '80s and the '90s, sperm concentration and motility showed a
      significant reduction. Furthermore, the decrease in concentration and motility
      was mainly due to the higher age classes. In donors, no decline was observed.
      These results seem to indicate that sperm donors remain unaffected, while
      patients with lower levels of semen quality are experiencing a real decline.
      Unfortunately, many confounding variables, analyzed in detail in this review,
      still remain despite efforts at standardization.

PMID- 10908170
TI  - Mutations in the CYP21 B gene in a Chilean population with simple virilizing
      congenital adrenal hyperplasia.
AB  - Steroid 21-hydroxylase deficiency (21OHD) compromises about 95% of all cases of
      congenital adrenal hyperplasia. We have characterized the disease-causing
      mutations in the steroid 21-hydroxylase genes of 19 Chilean patients (12 females
      and 7 males) with the simple virilizing (SV) form of 21OHD and compared them with
      other SV-populations. Using allele-specific polymerase chain reaction, we
      identified lesions in 28 chromosomes out of 38 tested (73.7%). The most frequent
      finding was the mutation I173N=12/38 (31.6%) similar as described in Caucasian,
      Asian and other Hispanic populations, where this mutation represents around 20
      40% of the genetic defects in the CYP21B gene. The mutation V282L=4/38 (10.5%)
      and deletion (Del) or large gene conversion (LGC)=3/38 (7.9%) were also
      frequently detected. Only 2 alleles carried the mutation I2 splice (5.3%), this
      frequency is lower than that reported in Caucasian or in Mexican populations. We
      did not find alleles with the mutations R357W, Cluster E6, P31L and P454S in
      these patients. The complete genotype was determined in 11/19 patients (58%) and
      one allele in 6/19 patients (31.6%). In summary, about 30% of the Chilean
      population with SV 21OHD presented the missense mutation I173N as described in
      other populations. The frequency of the other lesions showed differences even
      between populations with similar genetic background.

PMID- 10908172
TI  - "Portrait of gentlewoman". Jacopo de Barbari. Italy (1460/1470)-Bruxelles (before
      1516).

PMID- 10908171
TI  - Choosing the best pre-operative management for large pituitary adenomas. Emerging
      questions.

PMID- 10908174
TI  - Content of fragrance mix ingredients and customer complaints of cosmetic
      products.
AB  - BACKGROUND: In relation to the wide use of cosmetics, serious adverse effects are
      rare. Occasionally, unwanted effects such as contact dermatitis are reported.
      Allergic reactions to cosmetics are often caused by fragrances. OBJECTIVE: The
      aim was to investigate the content of fragrance mix (FM) ingredients in cosmetic
      products of the brand ACO HUD (Stockholm, Sweden) and the frequency of customer
      skin complaints about fragranced and unfragranced products over 4.5 years.
      METHOD: Content of FM ingredients in the fragrances used was both analyzed and
      requested from the suppliers. Customer complaints were those reported to the
      company. RESULTS: Between 1 and 7 of FM ingredients were present in levels of
      less than 0.1 to 770 ppm. The ingredients, in order of frequency, were geraniol,
      eugenol, hydroxycitronellal, alpha-amyl cinnamic aldehyde, isoeugenol, cinnamic
      alcohol, and oak moss. Cinnamic aldehyde was not found. No significant difference
      was found either between the frequency of complaints about products with and
      without fragrance (P = .21) or in a paired comparison of 17 formulas marketed
      with and without fragrance (P = .24). CONCLUSION: The study suggests that the
      investigated fragranced products had a low content of FM ingredients, which might
      explain the absence of a higher frequency of adversities. Furthermore, it appears
      that under such circumstances fragrances may be used without introducing an
      increased rate of spontaneous complaints of skin reactions.

PMID- 10908173
TI  - A skin sensitization risk assessment approach for evaluation of new ingredients
      and products.
AB  - Skin sensitization risk assessment of new ingredients or products is critical
      before their introduction into the marketplace. The risk assessment process
      described in this article involves evaluation of skin sensitization hazard,
      consideration of all potential human exposures, comparative ingredient/product
      benchmarking, and, when appropriate, the management of the risk. In this article,
      a risk assessment process is reviewed along with a description of the risk
      assessment tools that are employed for evaluating a new ingredient or product.
      The basic process we use for evaluating the skin sensitization risk of a new
      product or ingredient is considered a no effect/safety factor approach. The tools
      used for conducting a risk assessment include structure activity relationship
      analysis, exposure assessment, preclinical testing (e.g., local lymph node assay
      [LNNA]) and clinical testing (e.g., human repeat insult patch testing [HRIPT]).
      The skin sensitization risk assessment process described in this paper has been
      used successfully for many years for the safe introduction of new products into
      the marketplace. This process is dynamic--it can be applied to a diversity of
      product categories (e.g., shampoo, transdermal drug). In summary, the skin
      sensitization risk assessment process described in this article allows one to
      carefully assess the skin sensitization potential of a new ingredient or product
      so that it can be safely introduced into the marketplace.

PMID- 10908175
TI  - Sensitizing capacity of azole derivatives: Part III. Investigations with
      anthelmintics, antimycotics, fungicides, antithyroid compounds, and proton pump
      inhibitors.
AB  - BACKGROUND: More than hundred azole derivatives are used today for different
      purposes. The majority possess antimycotic, antibacterial, anthelmintic, and
      antiprotozoal properties. They are used as agricultural fungicides; topical
      antimycotics, and, for example, in antidandruff cosmetics. More recently the
      antithyroid and antiulcerative activity of certain imimidazoles and
      benzimidazoles also has been proven, which led to the introduction of proton pump
      inhibitors and antithyroid drugs to the market. OBJECTIVE: Case reports from the
      literature and experimental studies suggest that some of the azole derivatives
      possess a distinct sensitizing potency. Occupational exposure either in the
      pharmaceutical manufacture or in the pesticide's application by farmers caused
      allergic contact dermatitis (ACD). However, experimental studies in guinea pigs
      to determine their sensitizing capacity have been performed only sporadically.
      METHOD: Guinea pigs were sensitized by a modified Freund's complete adjuvant
      (FCA) method, with 35 azoles used as agricultural fungicides, proton pump
      inhibitors, antimycotics, antithyroid agents, antiprotozoals, antimicrobials,
      anthelmintics, and wood preservatives. RESULTS: Four azoles exhibited a strong
      sensitizing capacity, 3 a moderate, and 11 a weak sensitizing capacity. Seventeen
      derivatives remained negative. Among the strong sensitizers were the 3 proton
      pump inhibitors omeprazole, pantoprazole, and rabeprazole, as well as the
      antithyroid drug carbimazole. The latter displayed the highest sensitizing power
      (mean response = 2.50) of all 62 azole derivatives investigated in the present
      and the 2 previous experimental studies. CONCLUSION: As long as the strong
      sensitizing azoles are used only systemically the risk of acquiring contact
      hypersensitivity is low. However, if the idea should arise to use them topically,
      for example in ointments, tinctures, or lotions against fungal infections, skin
      problems will probably be observed abundantly.

PMID- 10908176
TI  - Solar urticaria: a report on 57 cases.
AB  - BACKGROUND: Solar urticaria (SU) represents an uncommon skin disorder,
      characterized by pruritic erythema and wheals after sun exposure, that sometimes
      restricts normal daily life. OBJECTIVE: To evaluate data concerning sex, age,
      natural history, associated diseases, and eliciting wavebands of 57 SU cases.
      METHODS: Questionnaire for anamnestic data, laboratory examinations,
      phototesting. RESULTS: Sex: 25 (44%) males, 32 (56%) females. Age: The peak age
      was between 20 and 30 years. Skin type (ST): 12 (21%) ST II, 39 (68%) ST III, and
      6 (11%) ST IV. Time between onset and complete disappearance of SU was from 2 to
      more than 6 years; the main peak (37 patients) between 4 and 6 years. There were
      histories of atopic dermatitis 12 (21%) and asthma or rhinitis 15 (26%).
      Association with other urticarias (U): 13 (21%) dermographic U, 2 food U, 3 heat
      U. Increased immunoglobin E (IgE): 19 (33%). Eliciting wavebands: 38 (67%)
      visible light (VIS), 16 (28%) long ultraviolet (UVA), 3 natural sunlight. Minimal
      urticarial dose (MUD): 20-37.5 J/cm2 for VIS-sensitive patients, 5-10 J/cm2 for
      UVA. CONCLUSIONS: In our series: 1. SU affects both sexes usually when they are
      under 30 years of age; 2. nearly half the patients are free of disease within 5
      years; 3. in about one fourth of cases SU is associated with dermographic
      urticaria or displays a history of atopic dermatitis; 4. the wheals are elicited
      mainly by VIS or UVA; 5. SU can be prevented, at least in part, by antihistamines
      or by PUVA therapy.

PMID- 10908177
TI  - Exuberant irritant reaction to paper tape.

PMID- 10908178
TI  - Allergic contact dermatitis to socks presenting as bleached rubber syndrome.

PMID- 10908179
TI  - Allergic contact dermatitis to epoxy resin in microscopy immersion oil: cases
      from Canada.
AB  - The presence of epoxy resin in a reformulated immersion oil for microscopy has
      caused an epidemic of occupational contact dermatitis in laboratory technicians
      from some European centers. We report 6 additional cases, the mode of
      presentation of which was similar to the European patients. All patients were
      patch tested to the undiluted oil, and some were tested to the European or North
      American standard series and to an extensive series of glues and adhesives
      allergens. At 96 hours, all 6 patients displayed a strong 2+ to 3+ reaction to
      the undiluted oil. Two patients were not further tested, but in the remaining 4,
      positive reactions were seen to epoxy resin from the standard tray. One patient
      reacted to cycloaliphatic epoxy resin, and 2 displayed positive tests to the
      reactive diluents phenyl glycidyl ether and cresyl glycidyl ether. These further
      cases confirm the strong sensitizing properties of this particular immersion oil.
      The product, manufactured by Leica Microsystems (Wetzlar, Germany), since has
      been withdrawn from sale.

PMID- 10908181
TI  - Oral lichen planus and the burning mouth syndrome. Is there a role for patch
      testing?
AB  - There is controversy about the role of contact allergy in the pathogenesis of
      oral lichen planus (OLP) and the burning mouth syndrome (BMS). Patients with OLP
      or BMS might wish to pursue allergy testing in hopes of identifying the cause of
      their disease. Although patch testing in these conditions might provide useful
      information, one risks discovering allergens of uncertain relevance. We asked 2
      experts in the field to discuss their approaches to evaluation and management of
      OLP and BMS, with an emphasis on the role of patch testing.

PMID- 10908180
TI  - Is it, or isn't it? Poison ivy look-a-likes.
AB  - Poison ivy causes more allergic contact dermatitis (ACD) than any other cause.
      Although physicians rightfully focus on the treatment of the dermatitis,
      prevention will be aided by recognition of the foreboding plant. Likewise, many
      other plants can masquerade as poison ivy and cause one to needlessly curtail his
      or her activities because of fear of a bad reaction. The most common poison ivy
      pretenders in the United States are discussed, and distinguishing plant
      characteristics are highlighted.

PMID- 10908182
TI  - Methylchloro-isothiazolinone revisited.
AB  - Preservatives are a class of allergens that is well represented in testing
      series. There are 5 preservatives in the TRUE test, 4 preservatives in the
      European series, and 13 in the North American Series.
      Methylchloroisothiazolinone/methylisothiozolinone (MCI/MI) (Kathon CG, Rohm and
      Haas, Spring House, PA) is a relatively new allergen that was introduced in 1980
      in the United States. Its use rapidly increased until reports of contact allergy
      became an issue. Allowable levels of MCI/MI in products, sensitivity rates, and
      use rates vary by country. The overall incidence of sensitivity for this
      allergen, as reported by the North American Contact Dermatitis Group, is similar
      to other allergens in the preservative class.

PMID- 10908183
TI  - Hazards of ethyl methacrylate.

PMID- 10908184
TI  - Patch testing for chromium sensitivity.

PMID- 10908185
TI  - Olfactory glia and CNS repair: a step in the road from proof of principle to
      clinical application.

PMID- 10908186
TI  - Physiological and pathological tremors and rhythmic central motor control.
AB  - In recent years there has been increasing interest in oscillatory neural activity
      in the CNS and in the role that such activity may have in motor control. It is
      thought that physiological tremor may be a manifestation in the periphery of such
      central oscillatory activity and that some pathological tremors are the result of
      derangement of these oscillators. This review re-evaluates both early and recent
      studies on physiological and pathological tremors and other peripheral
      oscillations in order to gain a new perspective on the nature and function of
      their central progenitors. This approach, namely using tremor as a 'window' into
      the function of central oscillations, is particularly suited to human
      investigations because of the obvious limitations of direct central recording. It
      is argued that physiological tremor is likely to be multifactorial in origin,
      with contributions not only from CNS 10-Hz range oscillatory activity, but also
      from motor unit firing properties, mechanical resonances and reflex loop
      resonances. Different origins are likely to dominate under different conditions.
      While some pathological tremors appear to arise as a distortion of central or
      peripheral components of physiological tremor, others arise de novo, such as the
      pathological oscillation of 3- to 6-Hz parkinsonian tremor. CNS oscillations
      outside the 10-Hz range are also found to modulate limb activity in normal
      individuals, and oscillatory activity exists in other motor systems such as eye
      movements. Finally, it is shown how studies of peripheral oscillations may help
      develop hypotheses on the role of CNS oscillations in motor control, including
      the proposed 'binding' function of synchronized oscillations and the possibility
      that motor signals could be coded by frequency of modulating oscillation as well
      as by synaptic connectivity.

PMID- 10908187
TI  - Essential tremor and cerebellar dysfunction clinical and kinematic analysis of
      intention tremor.
AB  - The cerebellum is assumed to play a major role in the pathophysiology of
      essential tremor (ET). As intention tremor is considered one of the classical
      features of cerebellar disease, we have assessed a large group of patients with
      ET for the semiology of the tremor and have performed objective quantitative
      analysis of a grasping movement in patients with ET, cerebellar disease and a
      normal control group. We found 25% of the patients to have a moderate or severe
      kinetic tremor with clear-cut features of a classical intention tremor. Another
      33% of the patients had a mild intentional component of their kinetic tremor.
      Patients with intention tremor (ET(IT)) did not differ from those with
      predominant postural tremor (ET(PT)) with respect to alcohol sensitivity of the
      tremor and the frequency of a family history. ET(IT) patients were older and more
      often showed head and trunk involvement. The onset of this intention tremor has
      been assessed retrospectively. It was found to begin at a randomly distributed
      time interval after the onset of the postural tremor, but older patients had a
      shorter time to development of intention tremor. Quantitative accelerometry of
      postural tremor showed similar tremor frequencies in both patient groups, but
      ET(IT) patients had a slightly larger tremor amplitude. Quantitative analysis of
      a grasping movement using an infrared-camera system was performed in two
      subgroups of the patients with ET(PT) and ET(IT) and control groups with
      cerebellar disease or normal subjects. The intention tremor could be quantified
      objectively as an increased amplitude of curvature during the deceleration and
      target phase of the movement. The amplitude measurements of intention tremor were
      clearly abnormal and of comparable magnitude for ET(PT) and cerebellar disease.
      Additionally, the patients with ET(IT) had a significantly slowed grasping
      movement during the deceleration and target period. Hypermetria was significantly
      increased for the patients with ET(IT) and cerebellar disease. We conclude that
      intention tremor is a feature of ET. ET(IT) patients have abnormalities of their
      upper limb function compatible with cerebellar disease. This suggests that
      patients with more advanced ET show abnormalities of cerebellar functions.

PMID- 10908188
TI  - Identification of a human olfactory ensheathing cell that can effect transplant
      mediated remyelination of demyelinated CNS axons.
AB  - The olfactory ensheathing cell (OEC) has attracted much interest recently because
      of its potential for transplantation-based therapy of CNS disease. Rat OECs are
      able to remyelinate demyelinated axons and support regeneration of damaged axons.
      Although OECs can be grown readily from the rat, a macrosmatic species, it has
      been uncertain whether it would be similarly straightforward to obtain these
      cells from the human, a microsmatic species with a relatively poorly developed
      olfactory system. In this study, we have identified a human OEC which shares many
      properties with its rat counterpart, including expression of the low-affinity
      nerve growth factor receptor (L-NGFr) and similar growth factor requirements.
      Purified populations of human OECs obtained by selection with L-NGFr antibodies
      have extremely high viability in tissue culture, and are capable of remyelinating
      persistently demyelinated CNS axons following transplantation into experimentally
      induced demyelinating lesions in the rat spinal cord. Thus, the human OEC
      represents an important new cell for the development of transplant therapy of CNS
      diseases.

PMID- 10908190
TI  - Activity-dependent conduction block in multifocal motor neuropathy.
AB  - Patients with multifocal motor neuropathy may complain of muscle fatigue, even
      though the degree of conduction block assessed at rest has improved with
      treatment. To explore the mechanism involved, we examined changes in muscle force
      during maximum voluntary contraction (MVC) and monitored conduction block before
      and after MVC in five patients with multifocal motor neuropathy. The results were
      compared with those for the contralateral unaffected homonymous muscles. For one
      patient, who had bilateral involvement, a normal subject of a similar age and
      stature served as the control. Results of conduction studies were also compared
      with those from six patients with amyotrophic lateral sclerosis (ALS) with
      similar compound muscle action potential (CMAP) amplitudes after proximal
      stimulation. During MVC for 60 s, the affected muscles developed prominent
      fatigue; the force at the end of contraction compared with the initial force was
      significantly lower for the affected muscles [42 +/- 19% (mean +/- standard
      deviation) of the initial force] than for the control muscles (94 +/- 9%; P =
      0.01). After MVC, the amplitude ratio of CMAPs after proximal versus distal nerve
      stimulation transiently decreased to 19 +/- 14% of that before MVC in the
      affected muscles, but not in the control muscles (94 +/- 3.8% of that before MVC)
      and in patients with ALS (95 +/- 6.7%). In one patient with a focal lesion in the
      forearm, nerve excitability was monitored at the lesion site before and after MVC
      for 120 s. There were significant increases in axonal threshold (approximately
      48%) and supernormality (approximately 135%) immediately after MVC, suggesting
      that the axonal membrane had undergone hyperpolarization and, by extrapolation,
      that this had precipitated the conduction block. This study is the first to show
      that activity-dependent conduction block plays a role in human disease by causing
      muscle fatigue.

PMID- 10908189
TI  - Auditory processing in the vegetative state.
AB  - H(2)(15)O-PET was used to investigate changes in regional cerebral blood flow in
      response to auditory stimulation in patients in the vegetative state. Five
      patients in a vegetative state of hypoxic origin were compared with 18 age
      matched controls. In addition, the cerebral metabolism of these patients and 53
      age-matched controls was studied using [(18)F]fluorodeoxyglucose. In control
      subjects, auditory click stimuli activated bilateral auditory cortices [Brodmann
      areas (BA) 41 and 42] and the contralateral auditory association cortices (BA
      22). In the patients, although resting metabolism was decreased to 61% of normal
      values, bilateral auditory areas 41 and 42 showed activation as seen in the
      controls, but the temporoparietal junction cortex (BA 22) failed to be activated.
      Moreover, the auditory association cortex was functionally disconnected from the
      posterior parietal association area (BA 40), the anterior cingulate cortex (BA
      24) and the hippocampus, as revealed by psychophysiological interaction analysis.
      Thus, despite altered resting metabolism, the auditory primary cortices were
      still activated during external stimulation, whereas hierarchically higher-order
      multi- modal association areas were not. Such a cascade of functional
      disconnections along the auditory cortical pathways, from the primary auditory
      areas to multimodal and limbic areas, suggests that the residual cortical
      processing observed in the vegetative state cannot lead to the integrative
      processes that are thought to be necessary for the attainment of the normal level
      of awareness.

PMID- 10908191
TI  - Phenotypic and genotypic heterogeneity in hereditary motor neuronopathy type V: a
      clinical, electrophysiological and genetic study.
AB  - We report on a large four-generation Austrian family with autosomal dominant
      distal hereditary motor neuronopathy type V (distal HMN V). Forty-seven at-risk
      family members, of whom 21 were definitely affected, underwent detailed clinical,
      electrophysiological and genetic studies. The age at onset was in the second
      decade of life in most affected individuals, but clinical presentation was rather
      variable. While the majority of patients were primarily disabled by progressive
      asymmetrical wasting of the thenar and the first dorsal interosseus muscles,
      others had marked foot deformity and gait disturbance with the occasional absence
      of hand involvement. Sensation sense was normal except for the reduced response
      to vibration. Many individuals showed brisk tendon reflexes and some elevated
      muscle tone in the lower limbs, but extensor plantar responses were rarely
      observed. Electrophysiological evaluation revealed normal or reduced motor nerve
      conduction velocities, normal or prolonged distal motor latencies, and low
      compound motor action potentials, depending on the degree of muscle wasting.
      Sensory nerve studies were usually within the normal range or slightly to
      moderately abnormal in older or severely affected persons. Electromyography
      showed high-amplitude motor unit potentials and reduced recruitment compatible
      with anterior horn cell degeneration. Central motor conduction times were
      prolonged in two-thirds of the patients. Molecular genetic studies excluded
      Charcot-Marie-Tooth 1A syndrome and proximal spinal muscular atrophy linked to
      chromosome 5q as well as the known gene loci for distal HMN II on chromosome 12q,
      HMN V on chromosome 7p and juvenile amyotrophic lateral sclerosis on chromosome
      9q. The findings in this family thus provide detailed clinical and
      electrophysiological information on HMN V and demonstrate broad phenotypic
      variability in this disorder. Hallmark features are discussed that appear to be
      most reliable to differentiate this type of HMN V from other variants of
      hereditary neuropathies, and a set of diagnostic criteria is proposed.
      Furthermore, this is the first report of prolonged central motor conduction times
      in HMN V, which indicates additional involvement of the central motor pathways in
      this disease. Finally, molecular genetic studies demonstrate genetic
      heterogeneity, suggesting the existence of at least a second genetic subtype in
      HMN V.

PMID- 10908192
TI  - Unconscious activation of visual cortex in the damaged right hemisphere of a
      parietal patient with extinction.
AB  - Visual extinction is a sign classically associated with right parietal damage.
      The patient can see a single stimulus presented in the ipsilesional or
      contralesional visual field, but is characteristically unaware of the same
      contralesional stimulus during simultaneous stimulation of both fields. The
      ipsilesional stimulus is said to 'extinguish' the contralesional stimulus from
      awareness during bilateral stimulation, perhaps due to a pathological bias in
      attention towards the ipsilesional side. Recent psychophysical evidence suggests
      that, although extinguished stimuli are not consciously seen, they may undergo
      residual processing and exert implicit effects on performance. However, the
      neural structures mediating such residual processing for extinguished stimuli
      remain unknown. Here we studied the neural activity evoked by an extinguished
      visual stimulus, using event-related functional MRI (fMRI), in a patient with
      circumscribed right inferior parietal damage and profound left-sided extinction.
      Monochrome objects (faces or houses) were presented in the left or right field,
      either unilaterally or bilaterally on each trial, with the patient indicating by
      button press whether he saw an object on the left, the right or on both sides. He
      usually saw only the right object on bilateral trials, yet the fMRI data showed
      activation of visual cortex contralateral to the extinguished left stimulus on
      these trials (compared with right-only stimulation), in both striate and early
      extrastriate areas of the right hemisphere. This activity had a similar location
      and time-course to that resulting from a single stimulus in the left versus right
      visual field. Cortical pathways involved in the normal processing of a single
      seen stimulus can thus still be activated by an unseen, extinguished stimulus
      after right parietal damage. Comparison of fMRI responses for faces versus houses
      revealed some category-specific activation for extinguished stimuli in right
      fusiform regions, but only at low statistical threshold. These results are
      discussed in terms of theoretical accounts for parietal extinction and, more
      generally, for the neural substrates of visual awareness.

PMID- 10908193
TI  - Transcortical sensory aphasia: revisited and revised.
AB  - Transcortical sensory aphasia (TSA) is characterized by impaired auditory
      comprehension with intact repetition and fluent speech. We induced TSA
      transiently by electrical interference during routine cortical function mapping
      in six adult seizure patients. For each patient, TSA was associated with multiple
      posterior cortical sites, including the posterior superior and middle temporal
      gyri, in classical Wernicke's area. A number of TSA sites were immediately
      adjacent to sites where Wernicke's aphasia was elicited in the same patients.
      Phonological decoding of speech sounds was assessed by auditory syllable
      discrimination and found to be intact at all sites where TSA was induced. At a
      subset of electrode sites where the pattern of language deficits otherwise
      resembled TSA, naming and word reading remained intact. Language lateralization
      testing by intracarotid amobarbital injection showed no evidence of independent
      right hemisphere language. These results suggest that TSA may result from a one
      way disruption between left hemisphere phonology and lexical-semantic processing.

PMID- 10908194
TI  - Distinguishing sensory and motor biases in parietal and frontal neglect.
AB  - Left neglect after right-hemisphere damage may involve perceptual and/or motor
      impairments. Here we discuss the limitations of previous attempts to separate
      these components, and introduce a new method. Six neglect patients (three with
      right inferior parietal lesions and three with right inferior frontal lesions)
      moved their right hand to a target light, which appeared unpredictably on either
      the left or the right of central fixation. The target appeared alone or with a
      distractor light in the opposite hemifield. Any directional motoric bias was
      measured by comparing reaches from a central start position with those for the
      same visual displays, but starting from the left of both possible targets (thus
      requiring only rightward reaches) or from the right (requiring only leftward
      reaches). All patients were slower to initiate reaches to left than right targets
      from a central start, which could reflect perceptual and/or motor biases.
      Critically, in the parietal neglect group only, initiation speed for left targets
      improved when a rightward reach was required to these (from a left start) rather
      than a leftward reach. This suggests a deficit in programming leftward movements
      into left hemispace, in addition to any visual impairment, for parietal neglect.
      A control task confirmed that this effect of start position was due to the
      associated change in reach direction and not to afferent inputs from the hand as
      it rested at the start position. Frontal neglect patients were slow to execute
      reaches to left targets, regardless of movement direction. Right visual
      distractors slowed visual reaction times to left targets more than vice versa in
      frontal neglect patients, and likewise for reach execution times in parietal
      neglect patients, suggesting that visual distractors on the neglected side have
      less impact. Distractor effects were unaffected by start position in the frontal
      neglect group (suggesting a perceptual basis), but distractors slowed reach
      initiation in the parietal neglect group only from left and central starts. Taken
      together, these findings demonstrate a directional motor component to parietal
      but not frontal neglect, and suggest that in man the inferior parietal lobe plays
      a role not only in perception but also in the programming of selective reaches.
      These conclusions are related to recent single-unit data from the monkey parietal
      lobe.

PMID- 10908196
TI  - The pathogenesis of lesions and normal-appearing white matter changes in multiple
      sclerosis: a serial diffusion MRI study.
AB  - The idea that the initiating event in the formation of all new multiple sclerosis
      lesions is a focal blood-brain barrier (BBB) leakage associated with perivascular
      inflammation has been challenged recently by the observation of subtle
      abnormalities in some quantitative magnetic resonance (MR) parameters (including
      the magnetization transfer ratio) prior to lesion enhancement. MR diffusion
      imaging can non-invasively quantify the average apparent diffusion coefficient
      (ADC(av)), a measure of water molecule random motion that is sensitive to
      pathological change in multiple sclerosis lesions and to abnormalities in the
      normal-appearing white matter (NAWM). We therefore used MR diffusion imaging to
      investigate the dynamic evolution of water diffusion measurements in new
      enhancing multiple sclerosis lesions, in the NAWM from which they arise, and in
      anatomically matched contralateral NAWM regions from which no visible lesions
      develop. Gadolinium diethylenetriaminepentaacetic acid (Gd)-enhanced MRI and MR
      diffusion studies were performed monthly for 1 year in five multiple sclerosis
      patients with clinically and radiologically active disease. The ADC(av) was
      calculated at each time point of the study (before, during and after lesion
      appearance on Gd-enhanced scans) for each new enhancing lesion, and for regions
      matched for size and position in the contralateral NAWM. A steady and moderate
      increase in ADC(av) in prelesion NAWM was observed, which was followed by a rapid
      and marked increase at the time of Gd enhancement and a slower decay after the
      cessation of enhancement. In matched contralateral NAWM regions there was a
      significant but milder increase in ADC(av) at the time of the first noted lesion
      enhancement. These findings indicate that new focal lesions associated with frank
      BBB leakage are preceded by subtle, progressive alterations in tissue integrity
      beyond the resolution of conventional MRI. The increases in ADC(av) in
      anatomically matched contralateral regions after lesions have appeared supports
      the concept that structural damage in lesions causes damage or dysfunction in
      connected areas of NAWM.

PMID- 10908197
TI  - Epidemiology of multiple sclerosis in US veterans. VIII. Long-term survival after
      onset of multiple sclerosis.
AB  - Survival to 1996 was analysed for nearly 2500 veterans of World War II who were
      rated as 'service-connected' for multiple sclerosis as of 1956 by the then
      Veterans Administration. Survival from onset was defined for all white women and
      black men, and a random sample of white men. Median survival times from onset
      were 43 years (white females), 30 years (black males) and 34 years (white males).
      Crude 50-year survival rates were 31.5% (white females), 21.5% (black males) and
      16.6% (white males), but only the white females and white males were
      significantly different. A proportional hazard analysis was used to identify risk
      factors for mortality from multiple sclerosis onset year. Significant risk
      factors included male sex (risk ratio: 1.57), older age at onset (risk ratio:
      1.05 per year) and high socioeconomic status (risk ratio: 1.05 per socioeconomic
      status category). There were no statistically significant differences in survival
      following multiple sclerosis onset by race or latitude of place of entry into
      military service, both significant risk factors associated with the development
      of multiple sclerosis. Standardized mortality ratios utilizing national US data
      (for 1956-96) showed a marked excess for all three race-sex groups of multiple
      sclerosis cases, with little difference among them, but with a decreasing excess
      over time. Relative survival rates, used to compare the survival of multiple
      sclerosis cases with that of other military veterans, did not differ
      significantly by sex-race group, nor by latitude of place of entry into military
      service, but did differ significantly by socioeconomic class. The lack of
      difference in male and female relative survival rates suggests that the
      significant difference in survival between male and female multiple sclerosis
      cases is, at least in part, a result of sex per se and not the disease.

PMID- 10908195
TI  - Expression of the co-stimulatory molecule BB-1, the ligands CTLA-4 and CD28 and
      their mRNAs in chronic inflammatory demyelinating polyneuropathy.
AB  - To examine whether the Schwann cells in patients with autoimmune neuropathies
      have the potential to behave as professional antigen-presenting cells, we
      investigated the expression of the co-stimulatory molecules BB-1, B7-1 (CD80) B7
      2 (CD86) and their counter-receptors CD28 or CTLA-4 (CD152) at the protein and
      mRNA levels in sural nerve biopsies of patients with chronic inflammatory
      demyelinating polyneuropathy (CIDP), CIDP associated with human immunodeficiency
      virus infection (HIV-CIDP), IgM paraproteinaemic neuropathy and normal or non
      immune axonal neuropathy. In single- and double-labelling experiments, we used
      the S-100 antigen as a pan-Schwann cell marker, myelin-associated glycoprotein as
      a marker for myelinating Schwann cells and the fibrillary acidic protein as a
      marker for unmyelinating Schwann cells. The expression of the B7 family of
      molecules was limited to BB-1 and was observed only on the Schwann cells. There
      was constitutive expression of BB-1 on unmyelinating Schwann cells in all nerves
      studied. However, in CIDP and HIV-CIDP, but not the other diseases, there was
      prominent upregulation of BB-1 on the myelinating Schwann cells. The endoneurial
      T cells in the proximity of BB-1-positive Schwann cells expressed the CD28 or
      CTLA-4 counter-receptors. Reverse transcription-polymerase chain reaction
      confirmed that these ligands were upregulated only in CIDP. Because the
      myelinating BB-1-positive Schwann cells expressed HLA-DR antigen, the findings
      indicate that, in CIDP, Schwann cells possess the necessary markers to function
      as antigen-presenting cells.

PMID- 10908198
TI  - Presynaptic inhibition and homosynaptic depression: a comparison between lower
      and upper limbs in normal human subjects and patients with hemiplegia.
AB  - Presynaptic inhibition of Ia terminals and postactivation depression at the Ia
      fibre-motor neuron (MN) synapses were compared in the upper and lower limbs of
      both sides in subjects from different populations: 49 spastic patients with
      hemiplegia [mainly with a lesion in the middle cerebral artery (MCA) area], two
      tetraplegics and 35 healthy subjects. Presynaptic inhibition was assessed using
      D1 inhibition of the soleus and the flexor carpi radialis (FCR) H reflexes
      elicited by electrical stimuli applied to the nerve supplying antagonistic
      muscles, and postactivation depression was explored by varying the time interval
      between two consecutive H reflexes. In normal subjects no right-left asymmetry
      was found in the amount of presynaptic Ia inhibition, homosynaptic depression or
      the H(max)/M(max) ratio. In the hemiplegic side of patients with MCA area
      lesions, the H(max)/M(max) ratio was significantly increased in the soleus but
      not in the FCR. Presynaptic inhibition of Ia terminals, which was significantly
      reduced at the cervical level on the hemiplegic side (and also, but to a lesser
      extent, on the unaffected side), was unchanged at the lumbar level. Homosynaptic
      depression was similarly reduced at the cervical and lumbar levels on the
      hemiplegic side but not modified on the unaffected side. It is argued that the
      decrease in presynaptic inhibition of Ia terminals is more a correlate of
      spasticity than a mechanism underlying it. The decrease in postactivation
      depression, which very probably contributes to the exaggeration of the stretch
      reflex characterizing spasticity, might be a consequence of the changes in the
      pattern of activation of Ia afferents and MNs following the motor impairment.

PMID- 10908199
TI  - The development of cutaneous allodynia during a migraine attack clinical evidence
      for the sequential recruitment of spinal and supraspinal nociceptive neurons in
      migraine.
AB  - Recently, we showed that most migraine patients exhibit cutaneous allodynia
      inside and outside their pain-referred areas when examined during a fully
      developed migraine attack. In this report, we studied the way in which cutaneous
      allodynia develops by measuring the pain thresholds in the head and forearms
      bilaterally at several time points during a migraine attack in a 42-year-old
      male. Prior to the headache, he experienced visual, sensory, motor and speech
      aura. During the headache, he experienced photo-, phono- and odour-phobia, nausea
      and vomiting, worsening of the headache by coughing or moving his head, and
      cutaneous pain when shaving, combing his hair or touching his scalp. Comparisons
      between his pain thresholds in the absence of migraine and at 1, 2 and 4 h after
      the onset of migraine revealed the following. (i) After 1 h, mechanical and cold
      allodynia started to develop in the ipsilateral head but not in any other site.
      (ii) After 2 h, this allodynia increased on the ipsilateral head and spread to
      the contralateral head and ipsilateral forearm. (iii) After 4 h, heat allodynia
      was also detected while mechanical and cold allodynia continued to increase.
      These clinical observations suggest the following sequence of events along the
      trigeminovascular pain pathway of this patient. (i) A few minutes after the
      initial activation of his peripheral nociceptors, they became sensitized; this
      sensitization can mediate the symptoms of intracranial hypersensitivity. (ii) The
      barrage of impulses that came from the peripheral nociceptors activated second
      order neurons and initiated their sensitization; this sensitization can mediate
      the development of cutaneous allodynia on the ipsilateral head. (iii) The barrage
      of impulses that came from the sensitized second-order neurons activated and
      eventually sensitized third-order neurons; this sensitization can mediate the
      development of cutaneous allodynia on the contralateral head and ipsilateral
      forearm at the 2-h point, over 1 h after the appearance of allodynia on the
      ipsilateral head. This interpretation calls for an early use of anti-migraine
      drugs that target peripheral nociceptors, before the development of central
      sensitization. If central sensitization develops, the therapeutic rationale is to
      suppress it. Because currently available drugs that aim to suppress central
      sensitization are ineffective, this study stresses the need to develop them for
      the treatment of migraine.

PMID- 10908200
TI  - Role of primary sensorimotor cortices in generating inhibitory motor response in
      humans.
AB  - To clarify the mechanism by which inhibitory motor responses such as cortical
      negative myoclonus are generated in humans, three patients with medically
      intractable partial epilepsy (two with frontal lobe epilepsy and one with
      parietal lobe epilepsy) were studied by means of direct cortical stimulation with
      a single electric pulse through subdural electrodes. All underwent chronic long
      term video/EEG monitoring, cortical mapping by 50 Hz electric cortical
      stimulation and recording of cortical somatosensory evoked potentials with
      chronically implanted subdural grid electrodes (3 mm in diameter and centre-to
      centre distance of 1 cm) to map both epileptogenic and functional zones. After
      these clinical evaluations, cortical stimulation by single electric pulse (0.3 ms
      duration, 1 Hz) was carried out through pairs of subdural electrodes located at
      the primary sensorimotor area (MI-SI), pre-supplementary motor area (pre-SMA) and
      lateral negative motor area (lateral NMA), while surface EMG was recorded from
      the muscles of the contralateral hand. The results showed that (i) in all
      subjects, single pulse stimulation of MI-SI elicited a motor evoked potential
      (MEP) followed by a silent period (SP) in the contralateral distal hand muscles,
      the latter lasting 300 ms after the stimulus. The duration of SP was proportional
      to the size of the preceding MEP. In one subject, SP without any preceding MEP
      was elicited, and, in another subject, there was a short SP immediately before
      MEP in the contralateral thenar muscle. (ii) Following the stimulation of either
      pre-SMA or lateral NMA, no SP was observed. It is concluded that the inhibitory
      mechanism within the MI-SI, but probably not in the non-primary motor areas,
      either closely linked to or completely independent of excitation, most likely
      plays an important role in eliciting brief negative motor phenomena such as
      cortical negative myoclonus or SP.

PMID- 10908201
TI  - Episodic memory in left temporal lobe epilepsy: a functional MRI study.
AB  - Left medial temporal lobe epilepsy (MTLE) is associated with verbal memory
      impairment usually related to hippocampal damage. We used functional MRI (fMRI)
      to investigate the patterns of functional activity in healthy volunteers and MTLE
      patients engaged in verbal episodic memory tasks to look for evidence of a
      reallocation of verbal memory in epileptic patients. fMRI data were collected
      from seven MTLE patients with left-sided hippocampal sclerosis and 10 healthy
      right-handed control subjects on a 3T scanner. Subjects were instructed to learn
      a list of 17 words (encoding) and then to recall them (retrieval) on successive
      trials. Healthy volunteers and patients both exhibited bilateral activation
      (right higher than left) of the parahippocampal gyrus during the retrieval. This
      effect was more marked in the control subjects. In contrast to the control
      subjects, patients exhibited consistent and extensive left prefrontal activations
      in all the memory tasks. These findings show that verbal memory tasks did not
      involve the same functional patterns in patients and healthy volunteers. This may
      be interpreted as a dysfunctional response due to the epilepsy and left
      hippocampal sclerosis, and could reflect the early onset and progressive course
      of the disease.

PMID- 10908203
TI  - Books for review

PMID- 10908204
TI  - July 25, 2000

PMID- 10908202
TI  - Stereoelectroencephalography in focal cortical dysplasia: a 3D approach to
      delineating the dysplastic cortex.
AB  - Focal cortical dysplasia (FCD) is an increasingly recognized cause of intractable
      epilepsy. Surgical data suggest that the dysplastic cortex should be removed to
      obtain freedom from seizures, but the prognosis remains poor as FCD is difficult
      to delineate by imaging. We retrospectively analysed a series of 28 patients
      (aged 5-41 years, median 16.5 years) with FCD who had been investigated by
      stereoelectroencephalography (SEEG) between 1964 and 1995. Neurophysiological
      data were correlated with histological findings and surgical outcome. MRI was
      available for only seven patients. Severe partial epilepsy of early onset, pre
      existing neurological deficit (68%) and cognitive impairment were the main
      clinical features. FCD was distributed equally between all lobes except for the
      temporal lobe, and was found predominantly on the mesial aspect of the cerebral
      hemispheres. SEEG findings provided evidence of dysplastic tissue
      epileptogenicity, as demonstrated by intralesional rhythmic spike discharges, the
      onset of ictal discharges and a low epileptogenic threshold. The epileptogenic
      zone corresponded to histologically defined FCD in 82% of the cases. Despite the
      lack of adequate neuroimaging in most cases, 64% of the patients became seizure
      free after surgery. The main predictors of a favourable outcome were complete
      removal of the epileptogenic zone (P< 0.01) and complete removal of the
      dysplastic cortex (P< 0.01). These results emphasize the usefulness of
      neurophysiological data in accurately assessing the extent of the FCD.

PMID- 10908205
TI  - Training the next generation of biomedical researchers: challenges and
      opportunities.

PMID- 10908206
TI  - Biodegradable stents : "fulfilling the mission and stepping away".

PMID- 10908207
TI  - Association of Coronary Heart Disease Risk Factors with microscopic qualities of
      coronary atherosclerosis in youth.
AB  - BACKGROUND: This study examined whether atherosclerosis in young people is
      associated with the risk factors for clinical coronary heart disease (CHD).
      Methods and Results-Histological sections of left anterior descending coronary
      arteries (LADs) from 760 autopsied 15- to 34-year-old victims of accidents,
      homicides, and suicides were graded according to the American Heart Association
      (AHA) system and computerized morphometry. Risk factors (dyslipoproteinemia,
      smoking, hypertension, obesity, impaired glucose tolerance) were assessed by
      postmortem measurements. Approximately 2% of 15- to 19-year-old men and 20% of 30
      to 34-year-old men had AHA grade 4 or 5 (advanced) lesions. No 15- to 19-year
      old women had grade 4 or 5 lesions; 8% of 30- to 34-year-old women had such
      lesions. Approximately 19% of 30- to 34-year-old men and 8% of 30- to 34-year-old
      women had atherosclerotic stenosis > or =40% in the LAD. AHA grade 2 or 3 lesions
      (fatty streaks), grade 4 or 5 lesions, and stenosis > or =40% were associated
      with non-HDL cholesterol > or =4.14 mmol/L (160 mg/dL). AHA grade 2 or 3 lesions
      were associated with HDL cholesterol <0.91 mmol/L (35 mg/dL) and smoking. AHA
      grade 4 or 5 lesions were associated with obesity (body mass index > or =30
      kg/m(2)) and hypertension (mean arterial pressure > or =110 mm Hg). CONCLUSIONS: 
      Young Americans have a high prevalence of advanced atherosclerotic coronary
      artery plaques with qualities indicating vulnerability to rupture. Early
      atherosclerosis is influenced by the risk factors for clinical CHD. Long-range
      prevention of CHD must begin in adolescence or young adulthood.

PMID- 10908208
TI  - Probabilistic model for prediction of angiographically defined obstructive
      coronary artery disease using electron beam computed tomography calcium score
      strata.
AB  - BACKGROUND: Electron beam CT (EBCT) is an accurate, noninvasive method to detect
      and quantify coronary artery calcification, a marker of coronary artery disease
      (CAD). This investigation examined the accuracy of EBCT to detect obstructive CAD
      (> or =50% stenosis) and determined the optimal strata for quantity of coronary
      artery calcification to facilitate clinical decision-making. METHODS AND RESULTS:
      Clinical research patients (n=213) were examined with coronary angiography and
      EBCT (angiography group), and 765 research participants were examined with only
      EBCT (nonangiography group). Of the angiography group, 53% had obstructive CAD.
      After adjustment for verification bias, the estimated sensitivity and specificity
      for calcium score > or =1 were 97.0% and 72.4%, respectively. Likelihood ratios
      for strata of calcium score associated with obstructive CAD were calculated in
      each sex and 2 age groups. Among those > or =50 years old, the same 4 strata of
      EBCT calcium scores were identified in each sex; likelihood ratios ranged from
      0.03 (calcium score 0) to 12.85 (calcium score > or =200). The same 3 strata EBCT
      calcium scores were identified in each sex among those <50 years old; likelihood
      ratios ranged from 0.13 (calcium score 0) to 190 (calcium score > or =100).
      CONCLUSIONS: A calcium score > or =200 among those > or =50 years old and calcium
      score > or =100 among those <50 years old provided strong evidence that patients
      of either sex had obstructive CAD. A calcium score of 0 provided strong evidence
      that patients > or =50 years old did not have obstructive CAD.

PMID- 10908209
TI  - Effect of coumarins started before coronary angioplasty on acute complications
      and long-term follow-up: a randomized trial.
AB  - BACKGROUND: Coronary angioplasty frequently creates a thrombogenic surface, with
      subsequent mural thrombosis that may lead to acute complications and possibly
      stimulates the development of restenosis. Whether coumarins can prevent these
      complications is unclear. The objective of this open, randomized trial was to
      assess the clinical effect of coumarins started before coronary angioplasty and
      continued for 6 months. METHODS AND RESULTS: Before coronary angioplasty, 530
      patients were randomly assigned to aspirin plus coumarins and 528 patients to
      aspirin alone. At the start of the angioplasty, the mean international normalized
      ratio was 2.7+/-1.1; during follow-up, it was 3.0+/-1.1. At 30 days, the
      composite end point of death, myocardial infarction, target-lesion
      revascularization, and stroke was observed in 18 patients (3.4%) treated with
      aspirin plus coumarin compared with 34 patients (6.4%) treated with aspirin alone
      (relative risk, 0.53; 95% CI, 0.30 to 0.92). At 1 year, these figures were 14.3%
      and 20.3%, respectively (relative risk, 0.71; 95% CI, 0.54 to 0.93). The
      incidence of major bleeding and false aneurysm during hospitalization was 3.2%
      and 1.0%, respectively (relative risk, 3.39; 95% CI, 1.26 to 9.11). The benefit
      of coumarins was observed in both stented and nonstented patients. CONCLUSIONS:
      Coumarins in addition to aspirin started before PTCA and continued for 6 months
      was more effective than aspirin alone in the prevention of acute and late
      complications after coronary angioplasty. This benefit was accompanied by a small
      but significant increase in bleeding complications.

PMID- 10908210
TI  - Targeting patients undergoing angioplasty for thrombus inhibition: a cost
      effectiveness and decision support model.
AB  - BACKGROUND: In recent clinical trials, glycoprotein IIb/IIIa blockers have
      demonstrated effectiveness in preventing adverse events after angioplasty in high
      risk patients. However, uncertainty exists regarding the cost-effective selection
      of patients to receive antiplatelet therapy. METHODS AND RESULTS: All 4962
      patients at Emory University Hospitals who underwent coronary intervention
      procedures (n=6062) from 1993 to 1995 were studied. Multivariate models to
      predict death and the composite of death, Q-wave and non-Q-wave myocardial
      infarction, and emergency additional revascularization were developed. Hospital
      costs and professional costs were determined. A cost-effectiveness analysis with
      therapy targeted to high-risk patients was performed. If patients with a >5%
      probability of events received antiplatelet therapy that reduced events by 24%
      and cost $1000, 40.1% of patients would receive therapy; complications would be
      reduced from 6.39% to 5.37%, and cost would increase $261 from $10343 to $10604,
      or $25504 per event prevented. The marginal cost per event prevented by moving
      from a 7% to a 5% probability of an event cutoff would be $57 799. CONCLUSIONS:
      For high-risk patients, there may be cost savings; for low-risk patients, therapy
      may not be cost effective; and for patients in the midrange (between 5% and 7%
      probability of an adverse event), events may be prevented at an acceptable level
      of cost.

PMID- 10908211
TI  - Initial and 6-month results of biodegradable poly-l-lactic acid coronary stents
      in humans.
AB  - BACKGROUND: Although metallic stents are effective in preventing acute occlusion
      and reducing late restenosis after coronary angioplasty, many concerns still
      remain. Compared with metallic stents, poly-l-lactic acid (PLLA) stents are
      biodegradable and can deliver drugs locally. The aim of this study was to
      evaluate the feasibility, safety, and efficacy of the PLLA stent. METHODS AND
      RESULTS: Fifteen patients electively underwent PLLA Igaki-Tamai stent
      implantation for coronary artery stenoses. The Igaki-Tamai stent is made of a
      PLLA monopolymer, has a thickness of 0.17 mm, and has a zigzag helical coil
      pattern. A balloon-expandable covered sheath system was used, and the stent
      expanded by itself to its original size with an adequate temperature. A total of
      25 stents were successfully implanted in 19 lesions in 15 patients, and
      angiographic success was achieved in all procedures. No stent thrombosis and no
      major cardiac event occurred within 30 days. Coronary angiography and
      intravascular ultrasound were serially performed 1 day, 3 months, and 6 months
      after the procedure. Angiographically, both the restenosis rate and target lesion
      revascularization rate per lesion were 10.5%; the rates per patient were 6.7% at
      6 months. Intravascular ultrasound findings revealed no significant stent recoil
      at 1 day, and they revealed stent expansion at follow-up. No major cardiac event,
      except for repeat angioplasty, developed within 6 months. CONCLUSIONS: Our
      preliminary experience suggests that coronary PLLA biodegradable stents are
      feasible, safe, and effective in humans. Long-term follow-up with more patients
      will be required to validate the long-term efficacy of PLLA stents.

PMID- 10908212
TI  - Body composition and prevalence of left ventricular hypertrophy.
AB  - BACKGROUND: Fat-free mass (FFM) has been proposed as an optimal normalization of
      left ventricular (LV) mass to body size. We sought to evaluate the novel FFM
      based criteria of LV hypertrophy (LVH). METHODS AND RESULTS: A population sample
      of 1371 men and women aged 25 to 74 years was examined by echocardiography and
      bioelectrical impedance analysis. Internal partition values for LVH were
      generated in a healthy population subgroup on the basis of LV mass divided by FFM
      and by the traditional indexations to body height, height(2.7), and body surface
      area. In contrast to the sex-specific criteria required by traditional
      indexations, the value of LV mass/FFM that divided individuals with and without
      LVH was identical for men and women (4.1 g/kg). Estimates of LVH prevalence
      varied significantly by type of indexation used, internally or externally derived
      cut points, and by population subgroups. Differences were pronounced among
      hypertensives and the obese. Thus, the application of LV mass/FFM more than
      halved the risk of LVH in obese versus nonobese women (odds ratio, 2.5; 95%
      confidence interval, 1.6 to 4.0) compared with criteria based on LV
      mass/height(2.7) (odds ratio, 5.5; 95% confidence interval, 3.6 to 8.3).
      Implications among hypertensives were less marked. CONCLUSIONS: Indexation of LV
      mass to FFM eliminates sex-specific LVH criteria. The proportion of individuals
      defined as having LVH using the new criteria deviate markedly from traditional
      indexations. Prospective investigations will be needed to identify the prognostic
      implications of different indexations, especially in subgroups such as the obese.

PMID- 10908214
TI  - Electrophysiological mapping and ablation of intra-atrial reentry tachycardia
      after Fontan surgery with the use of a noncontact mapping system.
AB  - BACKGROUND: Atrial tachyarrhythmias are a complication of Fontan surgery.
      Conventional electrophysiological mapping and ablation techniques are limited by
      the complex anatomic and surgical substrate and a high arrhythmia recurrence
      rate. This study investigates the use of noncontact mapping to identify
      arrhythmia circuits and guide ablation in Fontan patients. METHODS AND RESULTS:
      Eleven arrhythmias were recorded in 6 patients. Noncontact mapping improved
      recognition of the anatomic and surgical substrate and identified exit sites from
      zones of slow conduction in all clinical arrhythmias. Radiofrequency linear
      lesions were targeted across these critical zones in 5 patients. One patient
      underwent surgical cryotherapy. Although immediate success was achieved in 3 of 5
      patients with radiofrequency ablation, 2 patients had a recurrence after a mean
      of 6.4 months of follow-up. The patient who underwent cryoablation remains free
      of arrhythmias. CONCLUSIONS: Noncontact mapping can identify arrhythmia circuits
      in the Fontan atrium and guide placement of ablation lesions. Arrhythmia
      recurrence is high, possibly because of inadequate lesion creation rather than
      inaccurate mapping and lesion targeting.

PMID- 10908213
TI  - Hemodynamic effects of Bosentan, an endothelin receptor antagonist, in patients
      with pulmonary hypertension.
AB  - BACKGROUND: Few treatments are available for isolated pulmonary hypertension
      (PHT), which has a high morbidity and mortality. This trial was designed to
      assess the hemodynamic effects of bosentan, an endothelin receptor antagonist, in
      patients with PHT, in which local overproduction of endothelin-1 (ET-1) is
      thought to play a pathogenic role. METHODS AND RESULTS: An open-label, dose
      ranging study was performed in 7 female patients with primary PHT (n=5) or
      isolated PHT associated with limited scleroderma (n=2). Infusions of 50, 150, and
      300 mg were administered at 2-hour intervals, and the hemodynamic responses were
      measured. Bosentan caused a dose-dependent fall in total pulmonary resistance (
      20.0+/-11.0%, P=0.01) and mean pulmonary artery pressure (-10.6+/-11.0%, P>0.05).
      However, there was also a fall in the systemic vascular resistance (-26.2+/
      12.8%, P<0.005) and mean arterial pressure (-19.8+/-14.4%, P<0.001). There was a
      slight increase in cardiac index (15+/-12%, P>0.05) and a dose-dependent rise in
      ET-1 but no significant change in other hemodynamic variables, gas exchange, or
      other vasoactive mediators. CONCLUSIONS: Intravenous bosentan is a potent but
      nonselective pulmonary vasodilator at the doses tested, even in patients
      resistant to inhaled nitric oxide. Transient increases in plasma ET-1 were
      observed, consistent with a blockade of endothelial ET(B) receptors. Systemic
      hypotension and other significant events during the study indicate that its
      intravenous use in patients with severe PHT may be limited. Implications for
      future trial design and studies of chronic oral treatment are discussed.

PMID- 10908215
TI  - Oral Beraprost sodium, a prostaglandin I(2) analogue, for intermittent
      claudication: a double-blind, randomized, multicenter controlled trial. Beraprost
      et Claudication Intermittente (BERCI) Research Group.
AB  - BACKGROUND: Beraprost sodium (BPS) is a new stable, orally active prostaglandin
      I(2) analogue with antiplatelet and vasodilating properties. We report the
      results of a phase III clinical trial of BPS in patients with intermittent
      claudication. METHODS AND RESULTS: Patients (n=549) with a pain-free walking
      distance of between 50 and 300 m were entered into a 4-week single-blind placebo
      run-in phase. Patients whose pain-free walking distance had changed by <25% were
      then randomized to receive either BPS (40 microg TID, n=209) or placebo (n=213)
      in a double-blind manner for 6 months. Pain-free and maximum walking distances
      were measured on the occasion of treadmill exercise tests performed at baseline
      and 1.5, 3, 4.5, and 6 months after randomization. Success was defined as an
      improvement of >50% in pain-free walking distance at month 6 and in > or =1
      earlier treadmill exercise test in the absence of critical cardiovascular events.
      Success was observed more frequently in the BPS group (43.5%) than in the placebo
      group (33.3%, P=0.036). Pain-free walking distances increased by 81.5% and 52.5%,
      respectively, in the BPS and placebo groups (P=0.001) and maximum walking
      distances by 60.1% and 35.0%, respectively (P=0.004). The incidence of critical
      cardiovascular events was 4.8% in the BPS group and 8.9% in the placebo group.
      CONCLUSIONS: These results show that BPS is an effective symptomatic treatment of
      patients with intermittent claudication. The beneficial effects of BPS on
      critical cardiovascular events should be confirmed in appropriate clinical
      trials.

PMID- 10908216
TI  - Deletion of a 5-cM region at chromosome 8p23 is associated with a spectrum of
      congenital heart defects.
AB  - BACKGROUND: Cytogenetic evidence suggests that the haploinsufficiency of > or =1
      gene located in 8p23 behaves as a dominant mutation, impairing heart
      differentiation and leading to a wide spectrum of congenital heart defects
      (CHDs), including conotruncal lesions, atrial septal defects, atrioventricular
      canal defects, and pulmonary valve stenosis. An 8p heart-defect-critical region
      was delineated, and the zinc finger transcription factor GATA4 was considered a
      likely candidate for these defects. We narrowed this region and excluded a major
      role of GATA4 in these CHDs. METHODS AND RESULTS: We studied 12 patients (7 had
      CHD and 5 did not) with distal 8p deletions from 9 families by defining their
      chromosome rearrangements at the molecular level by fluorescent in situ
      hybridization and short-tandem repeat analysis. Subjects with 8p deletions distal
      to D8S1706, at approximately 10 cM from the 8p telomere, did not have CHD,
      whereas subjects with a deletion that included the more proximal region suffered
      from the spectrum of heart defects reported in patients with 8p distal deletions.
      The 5-cM critical region is flanked distally by D8S1706 and WI-8327, both at
      approximately 10 cM, and proximally by D8S1825, at 15 cM. Neither GATA4 nor
      angiopoietin-2 (ANGPT2; a gene in 8p23 involved in blood vessel formation) were
      found to be deleted in some of the critical patients. We also found that CHDs are
      not related to the parental origin of deletion. CONCLUSIONS: Haploinsufficiency
      for a gene between WI-8327 and D8S1825 is critical for heart development. A
      causal relationship does not seem to exist between GATA4 and ANGPT2
      haploinsufficiency and CHDs.

PMID- 10908217
TI  - Myocardial blood flow and myocardial uptake of (201)Tl and (99m)Tc-sestamibi
      during coronary vasodilation induced by CGS-21680, a selective adenosine A(2A)
      receptor agonist.
AB  - BACKGROUND: We investigated the hemodynamic and coronary vasodilatory effects of
      CGS-21680, a potent selective adenosine A(2A) agonist, as well as its potential
      use as a new stress modality in combination with perfusion scintigraphy. METHODS
      AND RESULTS: A stenosis of the left anterior descending coronary artery (LAD) was
      produced in dogs to reduce the reactive hyperemic response to <20%. Adenosine and
      CGS-21680 were then separately infused to maximize left circumflex coronary
      artery (LCx) flow velocity. (201)Tl (0.5 mCi) and (99m)Tc-sestamibi (5 mCi) were
      injected at the maximal dose of CGS-21680. Heart rate decreased with adenosine
      but increased during CGS-21680 infusion (P<0.005). The decrease in systolic blood
      pressure was more prominent with adenosine than with CGS-21680 (P<0.005). In the
      control LCx zone, maximal myocardial blood flow (MBF) (measured by radioactive
      microspheres) increased 3.1-fold during adenosine infusion (P<0.005) and 3.8-fold
      during CGS-21680 infusion (P<0.005). In the stenotic LAD zone, MBF did not change
      significantly. During adenosine and CGS-21680 infusion, stenosis/control zone MBF
      ratios were comparable (0.32+/-0.11 versus 0.27+/-0.10, P=NS), and transmural
      (201)Tl and (99m)Tc-sestamibi count-activity ratios (0.48+/-0.11 and 0.51+/-0.09,
      respectively) were also comparable (P=NS). Myocardial scintigraphy uncovered
      perfusion defects in all dogs. CONCLUSIONS: CGS-21680 elicits coronary
      vasodilation comparable to that of adenosine and produces profound heterogeneity
      of MBF and of (201)Tl and (99m)Tc-sestamibi myocardial uptake, rendering it a
      promising agent for pharmacological myocardial perfusion imaging.

PMID- 10908218
TI  - Chronic 17beta-estradiol replacement increases nitric oxide-mediated vasodilation
      of guinea pig coronary microcirculation.
AB  - BACKGROUND: Estrogen is cardioprotective of the coronary circulation by
      mechanisms incompletely understood. This study determined the effect of chronic
      17beta-estradiol replacement on dilator responses to acetylcholine and sodium
      nitroprusside of the isolated coronary microcirculation. METHODS AND RESULTS:
      Adult female guinea pigs were ovariectomized, and a 21-day-release pellet
      containing 0.0, 0.1, 0.25, 0.5, or 1.0 mg 17beta-estradiol was implanted
      subcutaneously. Serum estradiol concentrations ranged from 3.9 to 74.9 pg/mL,
      increasing with the dose of estradiol. After 19 to 20 days, the animals were
      euthanized, and their hearts were removed and perfused with buffer at constant
      flow on an isolated heart apparatus. Both perfusion pressure and contractile
      force were measured in prostaglandin F(2alpha)-constricted hearts. Vasodilation
      to the cumulative addition of the endothelium-dependent agonist acetylcholine
      (10(-9) to 10(-5) mol/L) and the nitric oxide (NO) donor sodium nitroprusside
      (10(-9) to 10(-5) mol/L) was measured before and after NO synthesis inhibition by
      nitro-L-arginine (LNA, 10(-4) mol/L). Baseline coronary resistance was unaltered
      by estradiol, although LNA increased resistance in estradiol-treated hearts more
      than in ovariectomized controls. Chronic 17beta-estradiol increased sensitivity
      (measured by -log EC(50) values) but not maximal response to acetylcholine
      compared with ovariectomized controls. Differences were abolished by LNA at all
      doses of estradiol. Sodium nitroprusside-induced dilation was unaffected by
      estradiol replacement. CONCLUSIONS: Chronic 17beta-estradiol replacement, at
      doses producing hormone levels within the physiological range, enhances dilator
      sensitivity of the coronary microcirculation through enhanced NO production by
      the endothelium, independent of changes in NO sensitivity of the vascular smooth
      muscle. Thus, estradiol enhances NO production as a protective mechanism of the
      coronary microcirculation.

PMID- 10908219
TI  - Involvement of cytokines in the mechanism of whole-body hyperthermia-induced
      cardioprotection.
AB  - BACKGROUND: Hyperthermia increases cardiac tolerance to ischemia/reperfusion
      injury and activates manganese superoxide dismutase (Mn-SOD), an intrinsic
      radical scavenger, in myocardium in a biphasic manner. Tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1beta (IL-1beta) induced a biphasic
      cardioprotection that corresponded to the activation of Mn-SOD. However, a direct
      association between Mn-SOD activation in myocardium and the acquisition of
      tolerance to ischemia/reperfusion injury induced by hyperthermia and the
      involvement of the cytokines in the signal transduction pathway for the
      hyperthermia-induced cardioprotection have not yet been elucidated. METHODS AND
      RESULTS: Hyperthermia was induced in anesthetized rats by placement in a
      temperature-controlled water bath. At 0.5 and 72 hours after hyperthermia,
      ischemia was induced by occlusion of the left coronary artery for 20 minutes,
      followed by reperfusion for 48 hours. Inhibition of the increases in Mn-SOD
      content and activity 72 hours after hyperthermia by the administration of
      antisense oligodeoxynucleotides to Mn-SOD abolished the expected decrease in
      myocardial infarct size. The simultaneous administration of neutralizing
      antibodies to TNF-alpha and IL-1beta before hyperthermia abolished the biphasic
      cardioprotection and increase in Mn-SOD activity. CONCLUSIONS: The increase in Mn
      SOD activity mediated through the production of TNF-alpha and IL-1beta by whole
      body hyperthermia is important in the acquisition of early- and late-phase
      cardioprotection against ischemia/reperfusion injury in rats.

PMID- 10908220
TI  - Cardioprotective mechanism of ischemic preconditioning is impaired by postinfarct
      ventricular remodeling through angiotensin II type 1 receptor activation.
AB  - BACKGROUND: Activation of protein kinase C-linked receptors and subsequent
      opening of the mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel are crucial
      in preconditioning (PC). This study examined whether postinfarct ventricular
      remodeling interferes with the PC mechanism. METHODS AND RESULTS: Two weeks
      before isolation of hearts, rabbits underwent a sham operation or coronary
      ligation (COL) to induce remodeling. Isolated buffer-perfused hearts were
      subjected to 30-minute global ischemia/2-hour reperfusion, and infarct size was
      expressed as a percentage of the left ventricle (%I/LV), from which the scarred
      infarct by COL was excluded. Although %I/LV was similar in sham-operated and
      remodeled hearts (52.9+/-6.5% versus 45.8+/-5.2%), PC with 2 episodes of 5-minute
      ischemia protected sham-operated but not remodeled hearts (%I/LV=18.1+/-2.5%
      versus 54.8+/-2.9%, P<0.05). Infusion of valsartan (10 mg x kg(-1). d(-1), an
      angiotensin II type 1 (AT(1)) receptor blocker, for 2 weeks after COL prevented
      the ventricular remodeling and preserved the response to PC (%I/LV=27.4+/-3.8%),
      although valsartan alone did not change %I/LV. Diazoxide, a mitoK(ATP) channel
      opener, protected both sham-operated and remodeled hearts (%I/LV=14.1+/-3.1% and
      8.3+/-3.6%). CONCLUSIONS: The myocardium remodeled after infarction is refractory
      to PC, which is probably due to interruption of cellular signaling by PC upstream
      of mitoK(ATP) channels. An AT(1) receptor blocker is beneficial not only for
      suppression of ventricular remodeling but also for preservation of the PC
      mechanism.

PMID- 10908221
TI  - Localization of the slow conduction zone during reentrant ventricular
      tachycardia.
AB  - BACKGROUND: Reentrant ventricular tachycardia is sometimes difficult to treat
      effectively because localizing the slow conduction zone (SCZ) for catheter
      ablation may be problematic. It was hypothesized that a linear relationship
      exists between activating wave-front acceleration and deceleration in the SCZ
      and, respectively, contractions and expansions of the far-field extracellular
      signal, which could be used for SCZ localization. METHODS AND RESULTS: To test
      the hypothesis, a model was developed to approximate SCZ location on the basis of
      the time interval between activation at the recording site and shifts in
      electrogram far-field deflections. Electrograms were recorded during reentry from
      196 to 312 epicardial sites (canine model, 8 episodes). Activation maps of
      reentry were constructed to determine wave-front velocity, and piecewise linear
      adaptive template matching (PLATM) measured time shifts in far-field electrogram
      deflections. Linear trends of cycle length change often occurred during
      tachycardia (mean trend, +15 ms/96.8 cardiac cycles; r(2)=0.92). Alteration in
      the time interval for activation through the SCZ approximated the change in
      tachycardia cycle length (mean correspondence, 75.7%). The beginning and end
      times of far-field extracellular waveform time shifts measured by PLATM predicted
      the time from recording site activation to activation at the SCZ proximal and
      distal edges, respectively (mean absolute error with respect to activation
      mapping, 20.3 ms). CONCLUSIONS: During reentry, PLATM estimates the time interval
      from activation at any recording site near the circuit to SCZ activation. PLATM
      time intervals are convertible to arc lengths along the circuit for potentially
      more rapid and accurate update of a hand-held probe toward the SCZ for catheter
      ablation.

PMID- 10908222
TI  - Left ventricular hypertrophy: pathogenesis, detection, and prognosis.

PMID- 10908223
TI  - Images in cardiovascular medicine. Intravascular ultrasound for stent
      implantation in aortic dissection.

PMID- 10908224
TI  - Left ventricular electromechanical mapping in stunned myocardium.

PMID- 10908225
TI  - Frequency of atrial septal aneurysm in patients with cerebral ischemic events.

PMID- 10908226
TI  - Scientific conference on preventive nutrition.

PMID- 10908227
TI  - Relationship between delay in performing direct coronary angioplasty and early
      clinical outcome in patients with acute myocardial infarction.

PMID- 10908228
TI  - Prevalence of myocardial viability as detected by positron emission tomography in
      patients with ischemic cardiomyopathy.

PMID- 10908229
TI  - Chymase-dependent angiotensin II formation in human vascular tissue.

PMID- 10908230
TI  - Ibuprofen as effective as indomethacin for patent ductus arteriosus.

PMID- 10908231
TI  - Identifying failure to achieve complete (TIMI 3) reperfusion following
      thrombolytic treatment: how to do it, when to do it, and why it's worth doing.

PMID- 10908233
TI  - Responding to the requirements of the national service framework for coronary
      disease: a core data set for myocardial infarction.

PMID- 10908235
TI  - Intracoronary infusions and the assessment of coronary blood flow in clinical
      studies.

PMID- 10908236
TI  - Coronary heart disease trends in France and elsewhere.

PMID- 10908238
TI  - Biventricular pacing in patients with severe heart failure: has the time come?

PMID- 10908239
TI  - Images in cardiology. Mycotic pseudoaneurysm of the ascending aorta following
      aortic valve replacement.

PMID- 10908240
TI  - Why biventricular pacing might be of value in refractory heart failure?

PMID- 10908241
TI  - Tuberculous pericarditis and HIV infection.

PMID- 10908243
TI  - Clinical trials in cardiovascular medicine: are we looking for statistical
      significance or clinical relevance?

PMID- 10908244
TI  - Treatment of cardiac diseases: evidence based or experience based medicine?

PMID- 10908245
TI  - Images in cardiology. Anomalous origin of the left coronary artery from the non
      coronary sinus of Valsalva.

PMID- 10908246
TI  - Delay in calling for help during myocardial infarction: reasons for the delay and
      subsequent pattern of accessing care.
AB  - OBJECTIVE: To determine the reasons for delay in calling for help during acute
      myocardial infarction and the reasons for choice of first medical contact.
      DESIGN: Review of routine medical records and one to one semi-structured
      interviews. SETTING: Community survey in city of Glasgow, north of the river
      Clyde. PATIENTS: 228 men and 85 women aged between 25 and 65 years, respectively,
      who survived acute myocardial infarction between October 1994 and December 1996.
      RESULTS: Only 25% of the subjects made a call for help within one hour of the
      onset of coronary symptoms; in 40% the delay was greater than four hours.
      Symptoms were not recognised as coronary in origin in the majority of cases. In
      all cases where delay was more than one hour the main reasons for the delay were
      thinking that symptoms would go away or that they were not serious. Requesting
      the attendance of a general practitioner was the first course of action in the
      majority of cases (55%); the main reason given was that the patient believed this
      should always be the first course of action. Reluctance to call the emergency
      services reflected the belief that the symptoms were not serious enough to
      warrant an ambulance. CONCLUSIONS: Strategies to reduce patient delay times in
      this deprived urban population must focus on educating the public on the
      recognition and diversity of coronary symptoms and the benefits of presenting
      promptly to hospital by way of the emergency ambulance service.

PMID- 10908248
TI  - The impact of time to thrombolytic treatment on outcome in patients with acute
      myocardial infarction. For the CORE investigators (Collaborative Organisation for
      RheothRx Evaluation).
AB  - OBJECTIVES: To examine the impact of time to thrombolytic treatment on multiple
      acute outcome variables in a single trial of thrombolysis in acute myocardial
      infarction. DESIGN AND PATIENTS: Mortality and reinfarction rate were measured in
      2770 patients with acute myocardial infarction who received thrombolysis within
      12 hours in CORE, an international, dose ranging trial of poloxamer 188. Tc-99m
      sestamibi infarct size and radionuclide angiographic ejection fraction substudies
      included 1099 and 1074 patients, respectively. RESULTS: Time to thrombolysis,
      subgrouped by intervals (< 2, 2-4, > or = 4-6, and > or = 6 hours), was
      significantly associated with infarct size (median 15.0%, 18.5%, 22.0%, 18.5% of
      left ventricle; p = 0.033), mean (SD) ejection fraction (51.5 (12.0)%, 48. 3
      (13.9)%, 48.2 (13.3)%, 48.2 (15.0)%; p = 0.006), 35 day mortality (5.7%, 7.1%,
      7.9%, 12.5%; p = 0.0004), six month mortality (7.3%, 8. 6%, 10.4%, 15.5%; p <
      0.0001), and 35 day reinfarction rate (6.1%, 3. 2%, 4.0%, 0.9%; p = 0.0001).
      CONCLUSIONS: In this single large trial, the beneficial effect of time to
      thrombolysis on infarct size and ejection fraction was restricted to treatment
      given within two hours of symptom onset, while the effect on mortality was
      evident over all time intervals. Reinfarction rate was higher in patients treated
      with earlier thrombolysis.

PMID- 10908249
TI  - Failure of thrombolysis by streptokinase: detection with a simple
      electrocardiographic method.
AB  - OBJECTIVE: To determine whether simple, readily applicable ECG criteria will
      allow early prediction of inadequate (< TIMI 3) flow in the infarct related
      vessel in patients receiving thrombolytic treatment for acute myocardial
      infarction; and to determine the success of streptokinase in achieving adequate
      antegrade flow in the infarct related vessel two hours after starting treatment.
      DESIGN: Cohort study. SETTING: Regional cardiothoracic unit. PATIENTS: 100
      sequential patients with acute myocardial infarction. INTERVENTIONS: Coronary
      angiography two hours after the initiation of thrombolytic treatment, proceeding
      to rescue angioplasty for inadequate flow in the infarct related vessel where
      appropriate. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy of six ECG criteria for the
      detection of inadequate antegrade flow in the infarct related vessel. RESULTS:
      The ECG test that performed best as a positive test for < TIMI 3 flow in the
      infarct related vessel was < 50% resolution of the ST segment elevation in the
      worst lead and no accelerated idioventricular rhythm. This had a sensitivity of
      81%, specificity of 88%, positive predictive value of 87%, negative predictive
      value of 83%, and overall accuracy of 85%. CONCLUSIONS: Sensitive, specific, and
      simple ECG criteria are defined for diagnosing failure of thrombolytic treatment
      with streptokinase. These allow the early detection of patients at high risk of
      further adverse events from a persistently occluded vessel. They may be used
      without recourse to sophisticated equipment or complex analyses. Such patients
      can then be considered for alternative treatments or enrollment into appropriate
      research protocols.

PMID- 10908251
TI  - Changing the site of delivery of thrombolytic treatment for acute myocardial
      infarction from the coronary care unit to the emergency department greatly
      reduces door to needle time.
AB  - OBJECTIVE: To quantify the change in door to needle time when delivery of
      thrombolytic treatment of acute myocardial infarction was changed from the
      coronary care unit to the emergency department. DESIGN: A comparative
      observational study using prospectively collected data. SETTING: Coronary care
      unit and emergency department of an Australian teaching hospital. PARTICIPANTS:
      89 patients receiving thrombolysis in coronary care unit between June 1994 and
      January 1996, and 100 patients treated in the emergency department between April
      1997 and May 1998. INTERVENTIONS: From April 1997, by agreement between
      cardiology and emergency medicine, all patients with acute myocardial infarction
      receiving thrombolysis were treated by emergency physicians in the emergency
      department. MAIN OUTCOME MEASURE: Door to needle time measured from time of
      arrival at the hospital to start of thrombolysis. Other outcomes included pain to
      needle time and mortality. RESULTS: Median door to needle times were less for
      patients treated in the emergency department than in the coronary care unit (37
      minutes, 95% confidence interval (CI) 33 to 44 v 80 minutes, 95% CI 70 to 89,
      respectively; p < 0.0001). Door to needle time was under 60 minutes in 83% of
      emergency department patients and 26% of coronary care unit patients (57%
      difference, 95% CI 45% to 69%; p < 0.0001). Median pain to needle time was less
      for emergency department patients than for coronary care unit patients (161
      minutes, 95% CI 142 to 177 v 195 minutes, 95% CI 180 to 209; p = 0.004); times of
      less than 90 minutes occurred in 18% of emergency department patients v 1% of
      coronary care unit patients (17% difference, 95% CI 9% to 25%; p < 0.05). Overall
      mortality was similar in patients treated in the emergency department and the
      coronary care unit. CONCLUSIONS: With a collaborative interdepartmental approach,
      thrombolytic treatment of acute myocardial infarction was more rapid in the
      emergency department, without compromising patient safety. This should improve
      the outcome in patients with infarcts treated with thrombolytic agents.

PMID- 10908252
TI  - Angiographic assessment of prospectively determined non-invasive reperfusion
      indices in acute myocardial infarction.
AB  - OBJECTIVE: To investigate the value of non-invasive reperfusion indices in acute
      myocardial infarction, avoiding the possible need for acute coronary angiography
      and subsequent angioplasty. DESIGN: In a prospective angiographic study, seven
      potential ECG or clinical markers of reperfusion were analysed in 230 patients
      with acute myocardial infarction. In all patients two 12 lead ECGs were used: the
      ECG on admission and the ECG immediately before coronary angiography. Non
      invasive markers of reperfusion determined just before coronary angiography were
      prospectively correlated to thrombolysis in myocardial infarction (TIMI) flow.
      Data analysis correlated these non-invasive indices with coronary flow (analysis
      A: TIMI 2-3 v TIMI 0-1 flow; analysis B: TIMI 3 v TIMI 0-2 flow). RESULTS: A
      sudden decrease in chest pain was the most common sign of reperfusion (36%),
      followed by reduction in ST segment elevation by >/= 50% (30%), and the
      development of a terminal negative T wave (20%) in the lead with the highest ST
      segment elevation. Reduction in ST segment elevation by > or = 50% and the
      appearance of an accelerated idioventricular rhythm (AIVR) had the highest
      positive predictive value for reperfusion. For analyses A and B, the positive
      predictive values were 85% and 66% for resolution of ST segment elevation, and
      94% and 59% for AIVR, respectively. The presence of three or more non-invasive
      markers of reperfusion predicted TIMI 3 flow accurately in 80% of cases.
      CONCLUSIONS: The prospective use of non-invasive indices of reperfusion is
      simple, practical, and can be of value in assessing coronary patency in patients
      admitted with acute myocardial infarction. Using these indices, discrimination
      between TIMI 0-1 and TIMI 2-3 flow can be made with good accuracy. However, TIMI
      3 flow cannot be determined reliably. The use of such non-invasive indices
      depends on the goal of reperfusion.

PMID- 10908253
TI  - Images in cardiology. Enlargement of cardiac rhabdomyoma and myocardial ischaemia
      during corticotropin treatment for infantile spasm.

PMID- 10908254
TI  - Incidence, recurrence, and case fatality rates for myocardial infarction in
      southwestern France, 1985 to 1993.
AB  - OBJECTIVE: To assess the impact of incidence, recurrence, and case fatality rates
      for myocardial infarction on coronary heart disease mortality in southwestern
      France between 1985 and 1993. DESIGN: Toulouse-MONICA myocardial infarction
      register. SETTINGS AND PATIENTS: All subjects aged 35 to 64 years living in the
      French department of Haute-Garonne. INTERVENTIONS: All coronary artery disease
      events between 1985 and 1993. MAIN OUTCOME MEASURES: 7210 events collected by the
      register between 1985 and 1993. RESULTS: In men, adjusted attack, total, and out
      of hospital mortality decreased by 2% (95% confidence interval (CI), -3.8% to 
      0.1%), 6.2% (95% CI -8.4% to -4.0%), and 4.2% (95% CI -7.0% to -1.5%) a year,
      respectively (p < 0.05). Incidence and recurrence rates decreased by 2% (95% CI 
      4.1% to -0.1%, p < 0.05) and 1.9% (95% CI -5.9% to 2.2%) a year (NS). In women,
      attack, total, and out of hospital mortality decreased by 1.7% (95% CI -5.2% to
      1.8%), 4.8% (95% CI -9.6% to 0. 1%), and 2.6% (95% CI -9.4% to 4.1%) a year,
      respectively; incidence decreased by 2% (95% CI -6.5% to 2.5%) and recurrence
      increased by 1. 4% (95% CI -9.8% to 12.6%) a year (all NS). In men, total,
      incident, and recurrent 28 day case fatality decreased by 3.8% (95% CI -4.8% to 
      2.8%), 3.2% (95% CI -4.1% to -2.3%), and 6.4% (95% CI -9.5% to -3.3%) a year,
      respectively (p < 0.05). For women, the corresponding decreases were 3.3% (95% CI
      -6.1% to -0.6%), 3.3% (95% CI -13.2% to 6.6%), and 11.7% (95% CI -24.6% to 1.3%)
      a year, but only the decrease in total 28 day case fatality reached significance.
      In both sexes, the reduction in case fatality contributed nearly 70% of the
      decrease in myocardial infarction mortality. CONCLUSIONS: In southwestern France,
      the decrease in myocardial infarction mortality mainly reflects improvements in
      acute management rather than prevention.

PMID- 10908255
TI  - Endogenous endothelin maintains coronary artery tone by endothelin type A
      receptor stimulation in patients undergoing coronary arteriography.
AB  - OBJECTIVE: To examine the contribution of endothelin type A (ET(A)) receptor
      stimulation by endogenously generated endothelin-1 (ET-1) to the maintenance of
      coronary vascular tone in humans. DESIGN: Controlled clinical study. SETTING:
      Tertiary cardiovascular referral centre. PATIENTS: 14 subjects were studied,
      seven with normal coronary arteries and seven with coronary artery disease, mean
      (SEM) age, 53 (2) years. INTERVENTIONS: After diagnostic coronary arteriography,
      BQ-123 (a selective ET(A) receptor antagonist; 100 nmol/min) in 0.9% saline, was
      infused into the left coronary artery at a rate of 1 ml/min for 60 minutes. Eight
      control subjects received saline alone. MAIN OUTCOME MEASURES: Blood flow
      velocity in the left anterior descending coronary artery, measured using a
      Doppler flow guidewire; coronary arteriography performed at baseline and
      immediately at the end of the BQ-123 or saline infusion to measure the diameter
      of proximal and distal left anterior descending coronary artery segments.
      RESULTS: The diameter of the proximal segment increased by 6 (2)%, while that of
      the distal segment increased by 12 (3)% after BQ-123 (both p < 0.05 v baseline).
      Coronary blood flow increased from 75 (10) to 92 (10) ml/min and coronary
      vascular resistance decreased from 1.99 (0.36) to 1.44 (0. 22) mm Hg/ml/min after
      BQ-123 (both p < 0.05 v baseline). The response to BQ-123 of patients with and
      without coronary artery disease was similar. There was no effect of saline in the
      controls. CONCLUSIONS: Endogenously produced ET-1 contributes to the maintenance
      of basal coronary artery tone in humans by ET(A) receptor stimulation. The role
      of ET(B) receptors remains to be defined.

PMID- 10908257
TI  - Does angina vary with the menstrual cycle in women with premenopausal coronary
      artery disease?
AB  - OBJECTIVE: To determine whether angina in women with established coronary heart
      disease varies with changes in hormone concentrations during the menstrual cycle.
      DESIGN: Subjects were prospectively studied once a week for four weeks. SETTING:
      Cardiology outpatient department of tertiary referral centre. SUBJECTS: Nine
      premenopausal women, mean (SEM) age 38.89 (2.18) years, with established coronary
      heart disease, symptomatic angina, and a positive exercise test. MAIN OUTCOME
      MEASURE: Myocardial ischaemia as determined by time to 1 mm ST depression during
      symptom limited exercise testing. Position in the menstrual cycle was established
      from hormone concentrations. RESULTS: The early follicular phase, when oestradiol
      and progesterone concentrations were both low, was associated with the worst
      exercise performance in terms of time to onset of myocardial ischaemia, at 290
      (79) seconds; the best performance (418 (71) seconds) was when oestrogen
      concentrations were highest in the mid-cycle (p < 0.05). Similar trends were
      observed in other measured variables. Progesterone concentrations did not
      influence exercise performance. CONCLUSIONS: During the menstrual cycle
      myocardial ischaemia was more easily induced when oestrogen concentrations were
      low. This may be important for timing the assessment and evaluating treatment in
      women with coronary heart disease.

PMID- 10908259
TI  - Images in cardiology. Chronic bilateral carotid body tumours causing carotid
      sinus hypersensitivity: abolition of symptoms by permanent cardiac pacing.

PMID- 10908258
TI  - Comparison of the acute effects of pacing the atrial septum, right atrial
      appendage, coronary sinus os, and the latter two sites simultaneously on the
      duration of atrial activation.
AB  - OBJECTIVE: To compare the acute effects of right atrial appendage, atrial septal,
      coronary sinus os, and dual site pacing on the duration of atrial activation.
      METHODS: 20 patients with a variety of cardiac conditions underwent an
      intracardiac electrophysiological study. Electrograms were recorded from the
      right atrial appendage and at multiple sites within the coronary sinus. The
      duration of atrial activation was measured during pacing at the right atrial
      appendage, atrial septum, and coronary sinus os, and also during dual site
      stimulation. RESULTS: The duration of atrial activation with atrial appendage
      pacing was notably longer (p < 0.001) than with dual site, septal, or coronary
      sinus os pacing, but there were no significant differences in atrial activation
      times between these latter three pacing modes. When stimulating the atria at a
      cycle length of 500 ms, the mean (SD) duration of atrial activation was 145 (37)
      ms for right atrial appendage pacing, 93 (26) ms for dual site pacing, 96 (28) ms
      for septal pacing, and 98 (28) ms for coronary sinus os pacing. CONCLUSIONS:
      Assuming that the duration of atrial activation is an important determinant of
      predisposition to paroxysmal atrial fibrillation, atrial septal pacing or
      coronary sinus os pacing would appear to offer the same advantage as dual site
      pacing without the additional complexities associated with the latter pacing
      mode.

PMID- 10908256
TI  - Double blind randomised placebo controlled trial of adjunctive prednisolone in
      the treatment of effusive tuberculous pericarditis in HIV seropositive patients.
AB  - OBJECTIVE: To determine the effect of adjunctive prednisolone on morbidity,
      pericardial fluid resolution, and mortality in HIV seropositive patients with
      effusive tuberculous pericarditis. DESIGN: Double blind randomised placebo
      controlled trial. SETTING: Two medical school affiliated referral hospitals in
      Harare, Zimbabwe. PATIENTS: 58 HIV seropositive patients aged 18-55 years with
      tuberculous pericarditis. INTERVENTIONS: All patients received standard short
      course antituberculous chemotherapy and were randomly assigned to receive
      prednisolone or placebo for six weeks. MAIN OUTCOME MEASURES: Clinical
      improvement, echocardiographic and radiologic pericardial fluid resolution, and
      death. RESULTS: 29 patients were assigned to prednisolone and 29 to placebo.
      After 18 months of follow up there were five deaths in the prednisolone treated
      group and 10 deaths in the placebo group. Mortality was significantly lower in
      the prednisolone group (log rank chi(2) = 8. 19, df = 1, p = 0.004). Resolution
      of raised jugular venous pressure (p = 0.017), hepatomegaly (p = 0.007), and
      ascites (p = 0.015), and improvement in physical activity (p = 0.02), were
      significantly more rapid in the prednisolone treated patients. However, there was
      no difference in the rate of radiologic and echocardiographic resolution of
      pericardial effusion. CONCLUSIONS: Adjunctive prednisolone for effusive
      tuberculous pericarditis produced a pronounced reduction in mortality. It is
      suggested prednisolone should be added to standard short course chemotherapy to
      treat HIV related effusive tuberculous pericarditis.

PMID- 10908261
TI  - Images in cardiology. Diagnostic value of a subtherapeutic adenosine dose.

PMID- 10908260
TI  - Failure of thrombolysis: experience with a policy of early angiography and rescue
      angioplasty for electrocardiographic evidence of failed thrombolysis.
AB  - OBJECTIVE: To assess the outcome of a policy of emergency coronary angiography
      with or without rescue angioplasty in patients with acute myocardial infarction
      and ECG evidence of failed reperfusion after thrombolysis. DESIGN: A cohort
      study. SETTING: Regional cardiothoracic unit. PATIENTS: 197 patients with acute
      myocardial infarction fulfilling a simple ECG criterion of failed reperfusion.
      INTERVENTIONS: Emergency coronary angiography proceeding to rescue angioplasty
      for inadequate antegrade flow. MAIN OUTCOME MEASURES: Hospital mortality for all
      197 patients; incidence of successful and failed rescue angioplasty; need for
      additional revascularisation in those receiving rescue angioplasty compared with
      those not treated in this way. RESULTS: 197 patients had emergency angiography
      for ECG evidence of failed reperfusion; 156 patients received immediate rescue
      angioplasty. Overall hospital mortality for those undergoing rescue angioplasty
      was 11.5%. Rescue angioplasty achieved TIMI 2 (11) or TIMI 3 (124) in 135
      patients, who had a hospital mortality of 5.9%. Failure to achieve at least TIMI
      2 flow following rescue angioplasty occurred in 21 patients, with a hospital
      mortality of 48%. In the 41 patients in whom immediate rescue angioplasty was not
      performed, reinfarction or requirement for revascularisation occurred in 37%.
      Reinfarction occurred in three patients (1.9%) who had immediate rescue
      angioplasty. Hospital mortality for the whole cohort was 10.7%. CONCLUSIONS: A
      policy of emergency coronary angiography proceeding to rescue angioplasty where
      appropriate reduces mortality in a high risk group to a level less than expected
      for patients with acute myocardial infarction and ECG evidence of failed
      reperfusion. Unsuccessful rescue angioplasty is associated with a high mortality.

PMID- 10908263
TI  - Images in cardiology. Thromboembolic leg ischaemia as first manifestation of an
      unrecognised myocardial infarction.

PMID- 10908262
TI  - Reversible left ventricular dysfunction associated with raised troponin I after
      subarachnoid haemorrhage does not preclude successful heart transplantation.
AB  - Transient abnormalities in ECGs, echocardiograms, and cardiac enzymes have been
      described in the acute setting of subarachnoid haemorrhage. In addition, left
      ventricular dysfunction has been reported at the time of brain death. A patient
      with an acute subarachnoid haemorrhage who presented with raised troponin I (TnI)
      concentrations and diffuse left ventricular dysfunction is described. After
      declaration of brain death 32 hours later, the heart was felt initially not
      suitable for transplantation. A normal cardiac catheterisation, however, lead to
      successful transplantation of the donor heart. Raised catecholamine
      concentrations and metabolic perturbations have been proposed as the mechanisms
      leading to the cardiac dysfunction seen with brain death. This may be a biphasic
      process, allowing time for myocardial recovery and reversal of the left
      ventricular dysfunction. Awareness of this phenomenon in the acutely ill
      neurologic population needs to be raised in order to prevent the unnecessary
      rejection of donor hearts.

PMID- 10908265
TI  - Troglitazone decreases collagen accumulation in prediabetic stage of a type II
      diabetic rat model.

PMID- 10908264
TI  - Increased plasma lipoprotein (a) concentrations in Behcet's disease and its
      relation to vascular events.

PMID- 10908266
TI  - Images in cardiology. Emergency DDD pacing using a single lead, balloon tip
      catheter.

PMID- 10908267
TI  - Timing of aortic valve surgery.

PMID- 10908268
TI  - Fetal and infant markers of adult heart diseases.

PMID- 10908269
TI  - Treatment of atrial flutter.

PMID- 10908270
TI  - Secondary prevention of hypercholesterolaemia: results of an audit conducted in
      South Wales.
AB  - OBJECTIVE: To audit the standards of secondary prevention of coronary heart
      disease in postmyocardial infarction patients. DESIGN: Follow up audit, one year
      after acute admission with myocardial infarction. SETTING: University Hospital.
      SUBJECTS: For the initial admission, 153 patients were audited, with 84 patients
      contacted one year later. Demographic data, treatment status, and cholesterol
      levels were analysed both on admission and at follow up. INTERVENTIONS: Total
      cholesterol was checked at the audit time either in the hospital or in the
      doctor's surgery. MAIN OUTCOME MEASURES: Statin doses and cholesterol levels.
      RESULTS: Ninety six per cent of patients had their lipid profile performed on
      admission. Eighty three per cent of the patients with total cholesterol >/= 5
      mmol/l were discharged from the hospital on lipid lowering medication. Forty five
      per cent of the subjects who were followed up had cholesterol levels >/= 5 mmol/l
      at 1 year. There was a disproportionate use of low doses of statins (lower than
      those shown in effective trials: simvastatin 20 to 40 mg, pravastatin 40 mg) with
      a third of all patients on medication not achieving the targets at one year.
      CONCLUSION: There was a major improvement in the proportion of patients started
      on treatment compared with figures reported by previous studies. However, the
      titration of the statin doses to achieve the targets is still unsatisfactory.

PMID- 10908271
TI  - Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary
      hypertension.
AB  - Primary pulmonary hypertension is a rare disease of childhood, which carries a
      poor prognosis. Patients often present with severe exercise limitation, and
      untreated life expectancy is less than 1 year. Pharmacological intervention is
      directed towards reduction of the raised pulmonary artery pressure with
      vasodilator treatment, initially with calcium antagonists, although more recently
      long term prostacyclin treatment has shown benefit in some patients. Heart-lung
      transplantation remains an option for children with severe disease refractory to
      therapeutic treatment. A 4 year old Bangladeshi girl with dyspnoea, cyanosis, and
      signs of a low cardiac output, is described. Initial treatment with prostacyclin
      was gradually reduced, and maintenance treatment with oral sildenafil (Viagra;
      Pfizer) instituted. At follow up 3 months later, her exercise capacity was
      greatly improved and she continues to enjoy a good quality of life without
      obvious side effects. In view of the encouraging initial results, this may become
      an acceptable adjunct in treating this patient group.

PMID- 10908273
TI  - Appointment of new editor-in-chief

PMID- 10908272
TI  - Life threatening coronary artery spasm in childhood Kimura's disease.
AB  - A 13 year old boy is described with hypereosinophilia associated with Kimura's
      disease, who showed repeated life threatening syncopal attacks during daily
      activities or at rest. Coronary arteriography demonstrated small aneurysms with
      irregular vessel walls of both coronary arteries, and the absence of organic
      stenotic lesions. Infusion of a minimal dose of ergonovine into the right
      coronary artery induced severe spasm of the vessel. Ventricular fibrillation
      recurred even after administration of nifedipine and isosorbide was started, but
      was completely inhibited by prednisolone.

PMID- 10908274
TI  - Potential regulation of GnRH gene by a steroidogenic factor-1-like protein.
AB  - Steroidogenic factor-1 (SF-1) is a member of an orphan nuclear hormone receptor
      superfamily. It plays a critical role in the development and function of the
      hypothalamic-pituitary-gonadal and adrenal axis. However, whether SF-1 can
      regulate transcription of gonadotrophin-releasing hormone (GnRH) gene is not
      known. To examine this possibility, we first over-expressed SF-1 and found that
      it not only decreased steady state GnRH messenger ribonucleic acid (mRNA) levels
      but also reduced its promoter activity in GT1-7 neurons. The inhibitory effect of
      SF-1 was lost when the 5'-flanking region of GnRH gene containing two distal (
      1479 to -1474 bp and -1059 to -1054 bp) hexamers was deleted. Gel mobility shift
      assays showed that GT1-7 cell nuclear extracts contained a protein that formed a
      specific complex with synthetic oligonucleotides containing the two distal
      hexamers or a consensus SF-1 binding sequence. The migration of this complex was,
      however, slower than the complex formed with MA-10 cell nuclear extracts which
      were shown to contain a 53 kDa SF-1 protein. The addition of anti-SF-1 antibody
      supershifted the complex formed with MA-10, but not with GT1-7 cell nuclear
      extracts. The same antibody, however, detected a 60 kDa protein and immunostained
      nuclei of GT1-7 neurons. These results are consistent with GT1-7 neurons
      containing an SF-1-like protein that can bind to the distal hexamer sequences in
      the 5'-flanking region of rat GnRH gene to inhibit its transcription.

PMID- 10908275
TI  - Improved FSH sensitisation and aromatase assay in human granulosa-lutein cells.
AB  - Granulosa-lutein (GL) cells from follicular aspirates from women undergoing in
      vitro fertilization (IVF) treatment are usually refractory to follicle
      stimulating hormone (FSH) regarding the induction and/or maintenance of aromatase
      activity which converts androgens (e.g. testosterone) to oestrogens. The normal
      method of assaying FSH-stimulated aromatase activity in GL cell cultures is to
      add exogenous testosterone throughout the cell culture period and measure the
      secreted oestradiol. Thus under the conditions usually employed for studying FSH
      stimulated oestradiol secretion in GL cells, the 'total' FSH effect is dependent
      both on the decay of the aromatase concentration in culture relative to its
      induction/maintenance by FSH and on changes in its activity in the face of a
      declining substrate concentration as the exogenous testosterone is converted over
      several days to oestradiol. We have therefore used a technique for challenging
      the cells with testosterone (10 micromol/l) for just 2 h at the end of the normal
      longer-term culture period such that its concentration was essentially unchanged,
      thus ensuring that there was no depletion of the aromatase substrate and that the
      FSH stimulation phase could be performed independently of exogenous testosterone.
      Consequently, GL cells were incubated for 0, 24 and 48 h prior to stimulation
      with FSH (100 IU/l) for 24 h after which they were washed and challenged with
      testosterone for 2 h and the secreted oestradiol was assayed. Freshly isolated GL
      cells from women undergoing IVF were refractory to FSH but after preincubation
      were responsive such that there was a 3-14-fold increase over basal activity
      depending on the cell preparation. In conclusion, we have developed a simple 48 h
      procedure for sensitizing GL cells to FSH and established the conditions for
      optimizing the assay of aromatase activity independently from the effect of FSH
      on its induction.

PMID- 10908276
TI  - Nitric oxide induces apoptosis in the human corpus luteum in vitro.
AB  - The present study aimed to investigate the role of nitric oxide (NO) in
      regression of the human corpus luteum. We therefore examined the effect of both
      NO and human chorionic gonadotrophin (HCG) on luteal cell apoptosis, and Bcl-2
      production. The effect of NO on oestrogen production during corpus luteum
      regression was also studied. Slices from corpus luteum collected throughout the
      luteal phase were incubated for 4 h with the nitric oxide synthase (NOS)
      substrate, L-arginine (L-Arg, 1 mmol/l), the NOS inhibitor N-monomethyl-L
      arginine (L-NMMA) (1 mmol/l), or with HCG (10 IU/ml). Oestradiol concentrations
      were determined by radioimmunoassay; Bcl-2 concentrations were measured by enzyme
      linked immunosorbent assay; apoptosis was detected in-situ by terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labelling; and inducible
      nitric oxide synthase (iNOS) was assessed by immunohistochemistry. Consistent
      with our previous findings, L-Arg elicited an inhibitory action on the production
      of oestradiol (P< 0.05). The number of apoptotic cells increased (P<0.05) from
      early to late corpus luteum, as did the number of cells positive for the
      expression of iNOS. The percentage of apoptotic cells in mid and late luteal
      phase was increased by L-Arg (56% and 310% respectively; P <0.05), and decreased
      by L-NMMA and HCG. Although no changes were observed in Bcl-2 concentration
      during the corpus luteum life span, L-Arg inhibited, and HCG augmented, Bcl-2
      production (P<0.05) from mid and late corpus luteum cells in vitro. In summary,
      these results suggest that the opposite actions of L-Arg and HCG on human corpus
      luteum viability may, in part, be mediated by changes in the level of the anti
      apoptotic activities caused by oestradiol and Bcl-2 protein.

PMID- 10908277
TI  - Y chromosome microdeletions and germinal mosaicism in infertile males.
AB  - Molecular deletions of the Y chromosome long arm are a frequent cause of male
      infertility. Because these deletions are thought to be inherited from fathers
      without Y chromosome deletions, the question arises as to whether their
      relatively high incidence in the male population could be due to the existence of
      a mosaicism in somatic and/or germinal paternal cells. This study included a
      total of 181 infertile men, among whom 18 were found to have an abnormal
      karyotype. In the other 163, polymerase chain reaction (PCR) analysis detected
      nine (5.5%) Y chromosome microdeletions. Blood, spermatozoa or testicular cells
      from 47 men (27 oligozoospermia, 20 azoospermia), including six Y-deleted
      patients, were screened for mosaicism using double target fluorescence in-situ
      hybridization (FISH) with Y centromeric and deleted in azoospermia (DAZ) gene
      specific probes. Results indicated that: (i) percentages of double (intact Y
      chromosome) or single (deleted Y chromosome) fluorescent signals by FISH were in
      agreement with PCR data, thus demonstrating the reliability of the method; and
      (ii) a weak germ cell mosaicism was found in only two oligozoospermic patients,
      carrying 1.97 and 4.13% respectively of spermatozoa with a deleted Y chromosome.
      Further studies on larger populations are needed to evaluate precisely the
      incidence of Y deletion mosaicisms in infertile men.

PMID- 10908278
TI  - The effects of insulin, and insulin-like growth factors I and II on human ovarian
      follicles in long-term culture.
AB  - The aim of this study was to investigate the effects of insulin and insulin-like
      growth factors I and II (IGF-I and IGF-II) on human ovarian follicles in vitro.
      Ovarian cortical tissue slices (0.1-0.3 cm) were cultured for 7 or 14 days on an
      artificial extracellular matrix and with FSH. The ovarian tissue cultures were
      stimulated by insulin (33 ng/ml), IGF-I (20 or 50 ng/ml) or IGF-II (20 ng/ml).
      Combined effects of IGF-I (20 ng/ml) or IGF-II (20 ng/ml) and insulin (33 ng/ml)
      were also studied. Proliferating cell nuclear antigen (PCNA) was selected for
      immunohistochemical examination activation of the mitotic cell cycle in granulosa
      cells. After 1 week of culture the number of follicles had decreased in all
      cases. After 2 weeks of culture the number of healthy follicles had decreased
      dramatically in control cultures. However, the loss of follicles could be
      prevented with insulin and IGFs. The number of atretic follicles was
      significantly lower in insulin cultures compared with control cultures after 2
      weeks. The proportion of primary follicles was significantly increased in
      cultures treated with insulin, IGF-I (50 ng/ml) or IGF-II (20 ng/ml) compared
      with control cultures after 2 weeks. A similar effect was seen after co-treatment
      with IGF-II and insulin. There were significantly more PCNA-positive follicles in
      IGF-I cultures than in control cultures. These results suggest that insulin, IGF
      I and IGF-II may act as survival factors for early stage human follicles. IGFs
      may also be involved in activation of the mitotic cell cycle of granulosa cells.

PMID- 10908279
TI  - Evidence for the participation of beta-hexosaminidase in human sperm-zona
      pellucida interaction in vitro.
AB  - Mammalian sperm-zona pellucida (ZP) interaction is mediated by sperm lectin-like
      proteins and ZP glycoproteins. We have previously reported the participation of
      binding sites for N-acetylglucosamine (GlcNAc) residues in human sperm function,
      including sperm interaction with the ZP. Additionally, previous results from our
      laboratory suggested that some of these events may be mediated by the glycosidase
      N-acetylglucosaminidase (beta-hexosaminidase, Hex, in mammals). In this study, we
      report the possible participation of Hex in human sperm-ZP interaction. Human
      recombinant Hex (hrHex) was obtained by expression in a stable transfected CHO
      cell line. When the recombinant enzyme was present during hemizona (HZ) assays,
      the number of sperm bound per HZ was significantly reduced. The same result was
      obtained when HZ were preincubated with hrHex. Additionally, the presence of a
      Hex-specific substrate during the HZ assay produced the same inhibitory effect.
      These results suggest the participation of a sperm Hex in the interaction with
      human ZP in vitro.

PMID- 10908280
TI  - Transcription of homeobox-containing genes detected in cDNA libraries derived
      from human unfertilized oocytes and preimplantation embryos.
AB  - Genes containing the evolutionarily conserved homeodomain sequence encode a
      family of DNA-binding transcription factors whose functions are crucial for
      embryonic development in vertebrates, invertebrates and plants. We describe the
      detection and analysis of transcripts of homeobox-containing genes present in
      cDNA libraries generated from human unfertilized oocytes, single cleavage stage
      embryos (2-cell, 4-cell, 8-cell and blastocyst) and a 10-week old whole fetus.
      Using degenerate primers derived from sequences within helix 1 and helix 3 of the
      highly conserved region of the ANTENNAPEDIA:-class homeodomain, a 166 bp band was
      detected in all the cDNA libraries tested. Subcloning of the oocyte-derived band
      revealed that it contained a heterogeneous group of 166 bp fragments. Sequence
      analysis of 40 independent clones demonstrated the presence of HOXA7, HOXD8, and
      HOXD1 sequences, the ubiquitously expressed POU family member, OCT1, and HEX, a
      homeotic gene expressed in haematopoietic cells.

PMID- 10908281
TI  - Identification and partial characterization of differentially expressed mRNAs in
      normal human endometria and endometrial carcinomas by differential display RT
      PCR.
AB  - Differential display methodology was employed to examine and compare the mRNA
      species derived from normal endometrial tissue and endometrial carcinoma (grade
      3, stage III) tissue biopsies. Two cDNA sequences, one expressed in the tumour
      group only (T19) and the other expressed only in the normal group (N22), were
      selected for verification of differential expression by semi-quantitative reverse
      transcription-polymerase chain reaction (RT-PCR). The expression of N22 was
      restricted to the normal group, suggesting a possible tumour suppressing
      function. Sequence analysis of this fragment revealed a high degree of similarity
      to a human cDNA sequence of unknown function. The expression of T19 mRNA was
      observed in both normal and neoplastic tissues, however the relative abundance
      was significantly higher in endometrial carcinomas. Expression of T19 mRNA was
      further examined in a larger clinical sample set and was significantly increased
      in the tumours (n = 16), with a three-fold increase when compared with the normal
      endometria, n = 5 (Kruskal-Wallis analysis of variance, P<0.05). Subsequent
      sequence analysis of T19 revealed a high degree of similarity to the 3'
      untranslated region of a rat growth factor responsive gene, SM-20. Further
      characterization of these mRNA transcripts may lead to the identification of
      novel genes involved in endometrial tumourogenesis.

PMID- 10908282
TI  - Anti-CD9 monoclonal antibody-stimulated invasion of endometrial cancer cell lines
      in vitro: possible inhibitory effect of CD9 in endometrial cancer invasion.
AB  - Cell surface marker CD9 has been reported to play a role in inhibiting
      trophoblastic cell invasion. Since the invasive properties of cancer cells may
      resemble those of trophoblasts, we decided to investigate the role of CD9 in the
      invasion of endometrial cancer cells. In normal human endometrium, CD9 was found
      to be constitutively expressed on epithelial cells, as reported previously. While
      epithelial cells of endometrial hyperplasia (n = 5) were also positive for the
      expression of CD9, endometrial adenocarcinomas (n = 15) showed reduced
      expression. In order to clarify the significance of this reduced CD9 expression
      in endometrial cancer, an in-vitro invasion assay system was used to assess the
      effect of anti-CD9 monoclonal antibody (mAb) on the invasive properties of
      endometrial cancer cell line. Anti-CD9 mAb significantly enhanced invasion of the
      RL95-2 and Ishikawa cell lines, without affecting cell proliferation. Since CD9
      is associated with the integrin subunits beta(1), alpha(3) and alpha(6) in human
      endometrium, we investigated the functional relationship between CD9 and these
      integrins in the RL95-2 cell line. Monoclonal antibodies against the integrins
      beta(1), alpha(3) and alpha(6) inhibited RL95-2 cell invasion. However, anti-CD9
      mAb continued to show a stimulatory effect on RL95-2 cell invasion after
      treatment with anti-integrin alpha(3) mAb. In contrast, the anti-CD9 mAb had no
      effect after treatment with the mAb for integrins alpha(6) and beta(1). These
      findings indicate that CD9 is involved in regulating the invasive properties of
      endometrial carcinoma cells and that this effect is partially mediated by
      integrin subunits alpha(6) and beta(1). Thus, CD9 appears to be involved in the
      prevention of endometrial cancer invasion.

PMID- 10908283
TI  - Modulation of endometrial transformation in gonadotrophin-stimulated and
      unstimulated pseudo-pregnant rabbits: studies with the progesterone receptor
      antagonist, onapristone.
AB  - Advanced endometrial transformation often occurs in IVF and embryo transfer
      therapy after ovarian stimulation with gonadotrophins. One reason is probably the
      early rise in peripheral progesterone concentration after ovulation induction.
      Consequently, we studied in a rabbit model, whether the post-ovulatory
      application of the progesterone receptor antagonist, onapristone, could prevent
      such an advancement of endometrial transformation after stimulation with
      different gonadotrophin preparations. The inhibitory effect of onapristone on the
      endometrium is dependent upon the strength of ovarian stimulation. In
      unstimulated animals or animals treated with recombinant LH (nine corpora
      lutea/animal in both groups), secretory differentiation and proliferation of the
      endometrium was strongly inhibited by onapristone. After weak ovarian stimulation
      with a 3:1 mixture of FSH and LH (22 corpora lutea/animal), secretory
      differentiation was strongly inhibited, while proliferation was enhanced. After
      strong stimulation with either a 1:1 mixture of FSH and LH, or human menopausal
      gonadotrophin (HMG; >40 corpora lutea/animal), only limited inhibitory effects of
      onapristone on secretory transformation or proliferation could be detected. In
      conclusion, these graded effects of onapristone after stimulation with
      gonadotrophins, resemble the basic observations from which a therapeutic strategy
      emerges, to modulate the advanced endometrial transformation which occurs in many
      IVF patients after ovarian stimulation.

PMID- 10908284
TI  - Human myometrial cells in culture express specific binding sites for urinary
      trypsin inhibitor.
AB  - Urinary trypsin inhibitor (UTI), which is present in amniotic fluid, prevents
      uterine contractility during pregnancy possibly via specific binding protein
      mechanisms. To test for the presence of UTI binding sites on the cell surface, we
      prepared cultured myometrial cells obtained at biopsy from 12 pregnant women and
      performed binding, competition, and cross-linking experiments using a specific
      radiolabelled UTI as a ligand. We report for the first time two classes of
      binding sites of differing affinities. Scatchard analysis at 4 degrees C, using
      radioiodinated UTI, revealed that UTI binds to 35 000 high affinity binding
      sites/cell (K(d) = 9.1x10(-9) mol/l) and 450 000 lower affinity binding
      sites/cell (K(d) = 3.5x10(-7) mol/l) in cultured myometrial cells. It appears to
      be the low affinity site that is internalized, and this has been identified as a
      protein of approximately 45 kDa by cross-linking and immunoaffinity labelling
      studies. Monoclonal antibodies against the NH(2)-terminal fragment of UTI
      abrogated specific binding of this protein to the cells. Treatment of the cells
      with hyaluronidase resulted in >80% inhibition of the [(125)I]-labelled UTI
      binding to the cells. These data show that the UTI binding site, which is
      hyaluronidase sensitive, is expressed on the surface of human uterine myometrial
      cells to accumulate the UTI molecule during pregnancy.

PMID- 10908285
TI  - Inhibin and activin production and subunit expression in human placental cells
      cultured in vitro.
AB  - Inhibins and activins are dimeric proteins, with each subunit being one of three
      related protein subunits (alpha, betaA or betaB). The mRNA levels of these
      subunits were studied quantitatively during in-vitro differentiation of human
      cytotrophoblast cells into syncytium, using Northern blot analysis and semi
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis.
      The corresponding protein concentrations were determined by specific enzyme
      linked immunosorbent assays for inhibin A, B, pro alphaC and activin A in
      cellular protein extracts and culture medium (n = 5). Immunofluorescence studies
      showed syncytium formation after 48 h. The alpha subunit was present before
      plating and increased at 48 h (P<0.001) while the betaA subunit was weak before
      plating and increased at 24 h. The betaB subunit was not detected. With respect
      to corresponding protein synthesis, inhibin A (alpha + betaA) had risen after 48
      h in cellular protein extract and after 72 h in culture medium, while activin A
      (betaA + betaB) was detected after 24 h, with no significant variations in
      culture medium. There was a good correlation between inhibin A and alpha subunit
      expression (r = 0.736, P<0.001), as well as between activin A and betaA subunit
      expression (r = 0.755, P<0.001). This study showed that mRNA expression parallels
      protein synthesis of inhibin and activin in trophoblast cells. Inhibin A
      synthesis appears to be dependent on alpha subunit mRNA expression, rather than
      on the betaA subunit which controls activin A synthesis. This study has also
      shown that isolated cytotrophoblast cells do not produce dimeric inhibin.
      However, during the transformation of cytotrophoblast cells into syncytium, betaA
      subunit mRNA expression may be an indicator of cell aggregation, while alpha
      subunit mRNA expression may be an indicator of cell fusion.

PMID- 10908286
TI  - Oncostatin M is produced during pregnancy by decidual cells and stimulates the
      release of HCG.
AB  - Oncostatin M (OSM) is a member of the interleukin-6 superfamily and a
      multifunctional cytokine that effects the growth and differentiation of many
      different cell types. OSM concentrations in the sera of pregnant women were found
      to be significantly higher than those of non-pregnant women. Western blot
      analysis revealed that the OSM protein was present in the decidua and chorionic
      tissue in each trimester. Throughout pregnancy, the amount of the OSM protein in
      the decidua was larger than that in the chorionic tissue. Immunohistochemistry
      using an anti-OSM monoclonal antibody demonstrated that OSM was mainly localized
      in the decidual glands and stroma. OSM transcripts in the decidua and the
      chorionic tissue were detected during each trimester by reverse transcription
      polymerase chain reaction (RT-PCR). The regulation of human chorionic
      gonadotrophin (HCG) release by the placenta in first trimester stimulated with
      recombinant OSM was also investigated. Stimulation of the placenta by OSM
      augmented HCG release in a time- and dose-dependent manner. HCG release induced
      by recombinant human OSM was completely blocked by antibodies against OSM and the
      signal transducer, gp130, but only partially inhibited by antibodies against the
      leukaemia inhibiting factor (LIF) receptor. These results suggest that OSM
      molecules produced by decidual glands and stromal cells during pregnancy have an
      important role in placental endocrine function.

PMID- 10908287
TI  - Placental endothelin gene expression and endothelin concentration in fetal fluids
      of the first trimester gestational sac.
AB  - We have investigated the distribution of immunoreactive endothelins (irET) in
      fetal fluids and expression of ET precursor genes in villous tissue during the
      first trimester. Samples of maternal plasma (n = 6), coelomic fluid (n = 28),
      amniotic fluid (n = 23) and villous tissue (n = 3) were obtained from 30
      pregnancies immediately before surgical termination at 7-12 weeks gestation. irET
      concentration was measured in plasma and fluids using two different
      radioimmunoassay kits, i.e. RPA 545 and RPA 555 and high performance liquid
      chromatography (HPLC). Total RNA was extracted and purified from villous tissue,
      reverse transcription and polymerase chain reaction (RT-PCR) were performed to
      evaluate the expression of ET-related genes. The irET concentration as evaluated
      by both kits was significantly higher (P<0.005) in maternal plasma than in
      coelomic or amniotic fluid and significantly higher (P<0.005) in coelomic fluid
      than in amniotic fluid using the RPA 555 kit. The profile of ET obtained by the
      HPLC- radioimmunoassay (RPA 555 kit) method confirmed significantly (P<0.005)
      higher ET concentration in coelomic than in amniotic fluid, although a similar
      distribution pattern for the three ET was observed in both embryonic fliud
      cavities. ET-3 was the predominant isoform in both fluids, reaching 19.4+/-2.0
      pg/ml and 6.3+/-1.6 pg/ml in coelomic and amniotic fluid, respectively. Coelomic
      or amniotic fluid irET concentration did not change with gestational age
      irrespective of the kit used. RT-PCR demonstrated that first trimester placenta
      expresses the genes encoding for prepro-ET-1, -ET-2 and -ET-3. The similar ET
      distribution pattern in both fluid cavities could reflect their origin from the
      villous tissue and suggests that ET may play a role in the development of
      placenta and other fetal organs during organogenesis.

PMID- 10908288
TI  - Placental leptin in normal, diabetic and fetal growth-retarded pregnancies.
AB  - Leptin expression in third trimester placenta (p) and leptin concentrations in
      umbilical cord blood (cb) were investigated in normal pregnancies [n = 10 (p), 31
      (cb)] and abnormal pregnancies complicated with (i) maternal insulin-dependent
      diabetes [IDDM: n = 3 (p), 13 (cb)], (ii) gestational diabetes [GD: n = 2 (p), 10
      (cb)] and (iii) fetal growth retardation [FGR: n = 5 (p), 5 (cb)]. By in-situ
      hybridization and immunohistochemistry, placental leptin mRNA and protein were co
      localized to the syncytiotrophoblast and villous vascular endothelial cells.
      Leptin receptor was immunolocalized to the syncytiotrophoblast. Relative to
      controls, the FGR group was characterized by low concentrations of placental and
      cord blood leptin. In a twin pregnancy, the normal-sized infant exhibited more
      placental and cord blood leptin than its growth-retarded twin. In contrast, both
      diabetic groups exhibited high concentrations of placental leptin mRNA and
      protein. The IDDM group exhibited the highest concentrations of leptin in cord
      blood. No change was observed in the expression of the leptin receptor in either
      the growth-retarded or diabetic pregnancies. In conclusion, the localization of
      placental leptin suggests that it may be released into both maternal and fetal
      blood. Furthermore, in fetal growth-retarded and diabetic pregnancies, the
      changes in leptin expression in the placenta and in leptin concentrations in
      umbilical cord blood appear to be related.

PMID- 10908290
TI  - Appointment of new editor-in-chief

PMID- 10908291
TI  - Dual expression and differential regulation of phosphodiesterase 3A and
      phosphodiesterase 3B in human vascular smooth muscle: implications for
      phosphodiesterase 3 inhibition in human cardiovascular tissues.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes whose
      physiological role is the attenuation of the signaling mediated by the ubiquitous
      second messengers cAMP and cGMP. Given the myriad of physiological processes
      regulated by cAMP and cGMP, PDEs have long been studied as potential therapeutic
      targets. Although phosphodiesterase 3 (PDE3) activity is abundant in human
      cardiovascular tissues, and acute PDE3 inhibition, with agents such as milrinone,
      was beneficial in heart failure patients, prolonged treatments were associated
      with time-dependent reductions in hemodynamic effects and increased mortality.
      The molecular basis of this time-dependent reduction in efficacy has not been
      elucidated. In this context, we used a combination of approaches to determine
      PDE3 expression in human cardiovascular tissues and to elucidate the effects of
      prolonged elevations of cellular cAMP, as would occur with PDE3 inhibition, on
      this activity. Although our data confirms the expression of PDE3A in human blood
      vessel smooth muscle cells (HASMCs), we identify a previously unrecognized role
      for PDE3B in cAMP hydrolysis in human cardiovascular tissues. Specifically,
      although both PDE3A and PDE3B were expressed in HASMCs, their subcellular
      expression pattern and regulated expression by cAMP were distinct, with only
      expression of PDE3B being subject to cAMP-regulated expression. Thus, a paradigm
      emerges that allows for dual expression, with distinctive regulation, of both
      PDE3A and PDE3B proteins in cardiovascular tissues that may have profound
      significance for the rational design of molecules regulating this PDE activity.

PMID- 10908292
TI  - Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine.
AB  - Retigabine is a novel anticonvulsant with an unknown mechanism of action. It has
      recently been reported that retigabine modulates a potassium channel current in
      nerve growth factor-differentiated PC12 cells (), however, to date the molecular
      correlate of this current has not been identified. In the present study we have
      examined the effects of retigabine on recombinant human KCNQ2 and KCNQ3 potassium
      channels, expressed either alone or in combination in Xenopus oocytes.
      Application of 10 microM retigabine to oocytes expressing the KCNQ2/3 heteromeric
      channel shifted both the activation threshold and voltage for half-activation by
      approximately 20 mV in the hyperpolarizing direction, leading to an increase in
      current amplitude at test potentials between -80 mV and +20 mV. Retigabine also
      had a marked effect on KCNQ current kinetics, increasing the rate of channel
      activation but slowing deactivation at a given test potential. Similar effects of
      retigabine were observed in oocytes expressing KCNQ2 alone, suggesting that KCNQ2
      may be the molecular target of retigabine. Membrane potential recordings in
      oocytes expressing the KCNQ2/3 heteromeric channel showed that application of
      retigabine leads to a concentration-dependent hyperpolarization of the oocyte,
      from a resting potential of -63 mV under control conditions to -85 mV in the
      presence of 100 microM retigabine (IC(50) = 5.2 microM). In control experiments
      retigabine had no effect on either resting membrane potential or endogenous
      oocyte membrane currents. In conclusion, we have shown that retigabine acts as a
      KCNQ potassium channel opener. Because the heteromeric KCNQ2/3 channel has
      recently been reported to underlie the M-current, it is likely that M-current
      modulation can explain the anticonvulsant actions of retigabine in animal models
      of epilepsy.

PMID- 10908293
TI  - Partial agonism through a zinc-Ion switch constructed between transmembrane
      domains III and VII in the tachykinin NK(1) receptor.
AB  - Partly due to lack of detailed knowledge of the molecular recognition of ligands
      the structural basis for partial versus full agonism is not known. In the beta(2)
      adrenergic receptor the agonist binding site has previously been structurally and
      functionally exchanged with an activating metal-ion site located between
      AspIII:08-or a His residue introduced at this position in transmembrane domain
      (TM)-III-and a Cys residue substituted for AsnVII:06 in TM-VII. Here, this
      interhelical, bidentate metal-ion site is without loss of Zn(2+) affinity
      transferred to the tachykinin NK(1) receptor. In contrast to the similarly
      mutated beta(2)-adrenergic receptor, signal transduction-i.e., inositol phosphate
      turnover-could be stimulated by both Zn(2+) and by the natural agonist, Substance
      P in the mutated NK(1) receptor. The metal-ion acted as a 25% partial agonist
      through binding to the bidentate zinc switch located exactly one helical turn
      below the two previously identified interaction points for Substance P in,
      respectively, TM-III and -VII. The metal-ion chelator, phenantroline, which in
      the beta(2)-adrenergic receptor increased both the potency and the agonistic
      efficacy of Zn(2+) or Cu(2+) in complex with the chelator, also bound to the
      metal-ion site-engineered NK(1) receptor, but here the metal-ion chelator complex
      instead acted as a pure antagonist. It is concluded that signaling of even
      distantly related rhodopsin-like 7TM receptors can be activated through Zn(2+)
      coordination between metal-ion binding residues located at positions III:08 and
      VII:06. It is suggested that only partial agonism is obtained through this simple
      well defined metal-ion coordination due to lack of proper interactions with
      residues also in TM-VI.

PMID- 10908294
TI  - The selective toxicity of 1-methyl-4-phenylpyridinium to dopaminergic neurons:
      the role of mitochondrial complex I and reactive oxygen species revisited.
AB  - 1-Methyl-4-phenylpyridinium (MPP(+)) is selectively toxic to dopaminergic neurons
      and has been studied extensively as an etiologic model of Parkinson's disease
      (PD) because mitochondrial dysfunction is implicated in both MPP(+) toxicity and
      the pathogenesis of PD. MPP(+) can inhibit mitochondrial complex I activity, and
      its toxicity has been attributed to the subsequent mitochondrial depolarization
      and generation of reactive oxygen species. However, MPP(+) toxicity has also been
      noted to be greater than predicted by its effect on complex I inhibition or
      reactive oxygen species generation. Therefore, we examined the effects of MPP(+)
      on survival, mitochondrial membrane potential (DeltaPsim), and superoxide and
      reduced glutathione levels in individual dopaminergic and nondopaminergic
      mesencephalic neurons. MPP(+) (5 microM) selectively induced death in fetal rat
      dopaminergic neurons and caused a small decrease in their DeltaPsim. In contrast,
      the specific complex I inhibitor rotenone, at a dose (20 nM) that was less toxic
      than MPP(+) to dopaminergic neurons, depolarized DeltaPsim to a greater extent
      than MPP(+). In addition, neither rotenone nor MPP(+) increased superoxide in
      dopaminergic neurons, and MPP(+) failed to alter levels of reduced glutathione.
      Therefore, we conclude that increased superoxide and loss of DeltaPsim may not
      represent primary events in MPP(+) toxicity, and complex I inhibition alone is
      not sufficient to explain the selective toxicity of MPP(+) to dopaminergic
      neurons. Clarifying the effects of MPP(+) on energy metabolism may provide
      insight into the mechanism of dopaminergic neuronal degeneration in PD.

PMID- 10908295
TI  - CYP2C40, a unique arachidonic acid 16-hydroxylase, is the major CYP2C in murine
      intestinal tract.
AB  - We recently identified five different murine CYP2C cDNAs from a murine cDNA
      library. When expressed in a bacterial cDNA expression system, all five
      recombinant proteins metabolized arachidonic acid but produced distinctly
      different profiles. In addition, some CYP2C mRNAs were found in extrahepatic
      tissues, as well as in liver. Immunoblots with an antibody raised against
      recombinant CYP2C38, which recognizes all five murine CYP2Cs, demonstrated that
      among extrahepatic tissues, colon and cecum contained the highest amount of
      CYP2Cs. The highest concentration of CYP2Cs occurred in cecum and colon (cecum
      >/= proximal colon >> distal colon), with lower levels in duodenum, jejunum, and
      ileum. Immunohistochemical studies revealed that CYP2Cs were localized
      principally in epithelial cells and autonomic ganglia in gut and colon.
      Polymerase chain reaction amplification of reverse-transcribed mRNA using murine
      CYP2C-specific primers followed by cloning and sequencing identified CYP2C40 as
      the major CYP2C isoform expressed in murine intestinal tract. Recombinant CYP2C40
      metabolized arachidonic acid in a regio- and stereospecific manner to 16(R)-HETE
      (hydroxyeicosatetraenoic acid) as the major product. To our knowledge, CYP2C40 is
      the first enzyme known to produce primarily 16-HETE. We conclude that CYP2C40 is
      one of the major cytochrome P450 proteins in the mouse intestinal tract. In the
      light of vasoactive and anti-neutrophilic effects of 16-HETE, we hypothesize that
      CYP2C40 may play an important role in endogenous biological functions in
      intestine.

PMID- 10908296
TI  - Characterization of naturally occurring and recombinant human N-acetyltransferase
      variants encoded by NAT1.
AB  - The genotype at the NAT1* locus of an interethnic population of 38 unrelated
      subjects was determined by direct sequencing of 1.6-kb fragments amplified by
      PCR. The coding exon alone and together with the 3' noncoding exon of the wild
      type (NAT1*4) and the three mutant alleles (NAT1*10, *11, and *16) detected was
      expressed in Escherichia coli and COS-1 cells, respectively, and the cytosolic
      fraction of mononuclear leukocytes from NAT1*4/*4 and NAT1*10/*10 homozygotes was
      also isolated. Recombinant and leukocyte cytosolic preparations were thoroughly
      characterized by N-acetylation activity with several NAT1-specific and -selective
      substrates, as well as by steady-state kinetics with varying amounts of the
      substrate (fixed acetyl CoA) and acetyl CoA (fixed substrate), thermodynamics,
      stability, and protein immunoreactivity with a polyclonal human anti-NAT1. The
      polyadenylation signal mutation in the 3' noncoding sequence of NAT1*10 affected
      none of the aforementioned parameters evaluated both with recombinant NAT1*10 and
      with the naturally occurring allele. Function was also unaffected by the coding
      and 3' noncoding exon mutations in NAT1*11. In contrast, the three extra
      adenosines located immediately after the sixth position of the polyadenylation
      signal in the 3' untranslated region of NAT1*16 ostensibly caused disruption of
      the predicted secondary structure of the pre-mRNA for NAT1 16, culminating in
      parallel 2-fold decreases in the amount and catalytic activity of NAT1 16 in COS
      1 cell cytosol. This novel finding in N-acetylation pharmacogenetics clearly
      demonstrates a direct link between reduced catalytic activity and structural
      alteration in the 3' untranslated region of an NAT variant (NAT1*16) brought
      about by mutation.

PMID- 10908297
TI  - Chick optic lobe contains a developmentally regulated alpha2alpha5beta2 nicotinic
      receptor subtype.
AB  - The most widely expressed neuronal nicotinic acetylcholine receptor subtype in
      chick brain is that containing the alpha4 and beta2 subunits. However,
      immunoprecipitation and localization studies have shown that some brain areas
      also contain the alpha2 and/or alpha5 subunits, whose role in the definition of
      receptor properties is still intriguing. Using subunit-specific polyclonal
      antibodies, we found that the optic lobe is the chick central nervous system
      region that expresses the highest level of alpha2-containing receptors.
      Immunoprecipitation studies of these immunopurified alpha2-containing receptors
      labeled with the nicotinic agonist [(3)H]epibatidine showed that almost all of
      them contained the beta2 subunit and that more than 66% contained the alpha5
      subunit. Western blot analyses of the purified receptors confirmed the presence
      of the alpha2, alpha5, and beta2 subunits and the absence of the alpha3, alpha4,
      alpha6, alpha7, alpha8, beta3, and beta4 subunits. The alpha2-containing
      receptors are developmentally regulated: their expression increases 25 times from
      embryonic day 7 to posthatching day 1 in the optic lobe, compared with an
      increase of only 5-fold in the forebrain. The alpha2-containing optic lobe
      receptors bind [(3)H]epibatidine (K(d) = 29 pM) and a number of other nicotinic
      agonists with very high affinity and have a pharmacological profile very similar
      to that of the alpha4beta2 subtype. They form functional cationic channels when
      reconstituted in lipid bilayers, with pharmacological and biophysical properties
      different from those of the alpha4beta2 subtype. These channels are activated by
      nicotinic agonists in a dose-dependent manner and are blocked by the nicotinic
      antagonist d-tubocurarine.

PMID- 10908298
TI  - alpha-bungarotoxin-sensitive nicotinic receptors indirectly modulate
      [(3)H]dopamine release in rat striatal slices via glutamate release.
AB  - Nicotinic agonists elicit the release of dopamine from striatal synaptosomes by
      acting on presynaptic nicotinic acetylcholine receptors (nAChRs) on dopamine
      nerve terminals. Both alpha3beta2* and alpha4beta2 nAChR subtypes (but not
      alpha7* nAChRs) have been implicated. Here, we compared nAChR-evoked
      [(3)H]dopamine release from rat striatal synaptosome and slice preparations by
      using the nicotinic agonist anatoxin-a. In the more integral slice preparation,
      the concentration-response curve for anatoxin-a-evoked [(3)H]dopamine release was
      best fitted to a two-site model, giving EC(50) values of 241 nM and 5.1 microM,
      whereas only the higher-affinity component was observed in synaptosome
      preparations (EC(50) = 134 nM). Responses to a high concentration of anatoxin-a
      (25 microM) in slices (but not in synaptosomes) were partially blocked by
      ionotropic glutamate receptor antagonists (kynurenic acid, 6,7-dinitroquinoxaline
      2,3-dione) and by alpha7*-selective nAChR antagonists (alpha-bungarotoxin, alpha
      conotoxin-ImI, methyllycaconitine) in a nonadditive manner. In contrast, the
      alpha3beta2-selective nAChR antagonist alpha-conotoxin-MII partially inhibited
      [(3)H]dopamine release from both slice and synaptosome preparations, stimulated
      with both low (1 microM) and high (25 microM) concentrations of anatoxin-a.
      Antagonism by alpha-conotoxin-MII was additive with that of alpha7*-selective
      antagonists. These data support a model in which alpha7* nAChRs on striatal
      glutamate terminals elicit glutamate release, which in turn acts at ionotropic
      glutamate receptors on dopamine terminals to stimulate dopamine release. In
      addition, non-alpha7* nAChRs on dopamine terminals also stimulate dopamine
      release. These observations have implications for the complex cholinergic
      modulation of inputs onto the major efferent neurons of the striatum.

PMID- 10908299
TI  - Involvement of hepatocyte nuclear factor 1 in the regulation of the UDP
      glucuronosyltransferase 1A7 (UGT1A7) gene in rat hepatocytes.
AB  - UDP-glucuronosyltransferase 1A7 (UGT1A7) is a major UGT contributing to the
      glucuronidation of xenobiotic phenols in rats. Its expression in rat liver is
      tightly regulated, with low constitutive and high inducible expression in
      response to aryl hydrocarbon receptor ligands and oltipraz. Previously, we
      reported the absence of 3-methylcholanthrene- or oltipraz-responsive elements in
      the 1.6-kbp region flanking the UGT1A7 promoter. However, potential binding sites
      were noted for several liver-enriched transcription factors. Here we show that
      deletion of the hepatic nuclear factor (HNF)3, HNF4, and CCAAT-enhancer binding
      protein-like binding sites had no effect on the expression of a UGT1A7 reporter
      plasmid, p(-965/+56)1A7-Luc, in primary rat hepatocytes. The full activity of the
      promoter was contained in the region between bases -157 and +76. Two sites of
      binding by rat liver nuclear proteins were detected in this region by DNase
      footprinting. PR-1 corresponded to the HNF1-like binding site between bases -52
      and -38, whereas PR-2 was located between -30 to -6. Gel retardation studies
      supported the presence of HNF1alpha in the PR-1 DNA-liver nuclear protein
      complex. Mutation of PR-1 inhibited binding in the gel shift assay, prevented
      activation by overexpressed HNF1 in human embryonic kidney cells, and reduced by
      >80% the maximal luciferase activities expressed from basal and 3
      methylcholanthrene-responsive UGT1A7 gene reporter constructs in primary rat
      hepatocytes. These data provide evidence for an important stimulatory role of
      HNF1 in promoting UGT1A7 gene expression in rat liver.

PMID- 10908300
TI  - Allelic variation S268P of the human mu-opioid receptor affects both
      desensitization and G protein coupling.
AB  - The decrease in mu-opioid receptor activity after chronic agonist exposure (1
      microM [D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin) is largely due to kinase
      mediated phosphorylation of intracellular receptor domains. We have recently
      shown that the substitution of two putative Ca(2+)/calmodulin-dependent protein
      kinase II (CaMK II) phosphorylation sites, S261 and S266, by alanines in the
      third intracellular loop of the rat mu-opioid receptor (rMOR1) confers resistance
      to CaMK II-induced receptor desensitization. In the present study, we show that
      the injection of active CaMK II in Xenopus laevis oocytes led to the
      desensitization of S261A but not S266A receptor mutant, indicating that S266 is
      the primary CaMK II phosphorylation site of the rMOR1. For the corresponding
      phosphorylation site in the human mu-opioid receptor (hMOR), an allelic variation
      S268P has been recently identified. After expression in X. laevis oocytes and
      human embryonic kidney 293 cells, this human S268P receptor and a corresponding
      rat S266P receptor mutant revealed a loss of CaMK II-induced receptor
      desensitization and a decreased G protein coupling compared with the wild-type
      receptors. Our results suggest that serines 266 (rMOR1) and 268 (hMOR) play
      crucial role in receptor desensitization and signaling and that the allelic
      variation S268P results in a human receptor type with a weaker but persistent G
      protein coupling after agonist treatment.

PMID- 10908301
TI  - Oatp2 mediates bidirectional organic solute transport: a role for intracellular
      glutathione.
AB  - One member of the OATP family of transporters, rat Oatp1, functions as an anion
      exchanger that is driven in part by the glutathione (GSH) electrochemical
      gradient, indicating that other OATP-related transporters may also be energized
      by this mechanism. The present study examined whether rat Oatp2 is also an anion
      exchanger, and, if so, whether it is energized by the GSH electrochemical
      gradient. As with Oatp1, uptake of 10 microM [(3)H]taurocholate in Oatp2
      expressing Xenopus laevis oocytes was trans-stimulated by intracellular 0.2 mM
      unlabeled taurocholate, indicating bidirectional transport. Interestingly,
      [(3)H]taurocholate uptake in Oatp2-expressing oocytes was also trans-stimulated
      when oocytes were preloaded with GSH, S-methylglutathione, S-sulfobromophthalein
      glutathione, S-dinitrophenyl glutathione, or ophthalmic acid (a GSH analog) but
      not by glutarate or N-acetylcysteine, suggesting that GSH derivatives and
      conjugates may function as intracellular substrates for Oatp2. Support for this
      hypothesis was provided by the demonstration of enhanced [(3)H]GSH and [(3)H]S
      (2,4-dinitrophenyl)-glutathione efflux in Oatp2-expressing oocytes. However, in
      contrast to Oatp1, extracellular GSH failed to cis-inhibit uptake of
      [(3)H]taurocholate or [(3)H]digoxin in Oatp2-expressing oocytes, indicating that
      the stimulatory effect of high intracellular GSH concentrations is not due to a
      coupled exchange mechanism. Taken together, the results indicate that Oatp2
      mediates bidirectional transport of organic anions by a GSH-sensitive
      facilitative diffusion mechanism and suggest that this transporter may play a
      role in cellular export of specific organic molecules.

PMID- 10908302
TI  - Steroid inhibition of rat neuronal nicotinic alpha4beta2 receptors expressed in
      HEK 293 cells.
AB  - Steroids, in addition to regulating gene expression, directly affect a variety of
      ion channels. We examined the action of steroids on human embryonic kidney 293
      cells stably transfected to express rat alpha4beta2 neuronal nicotinic receptors.
      Each steroid that was tested inhibited acetylcholine responses from these
      receptors, with slow kinetics requiring seconds for block to develop and recover.
      The action of one steroid [3alpha,5alpha, 17beta-3-hydroxyandrostane-17
      carbonitrile (ACN)] was studied in detail. Block showed enantioselectivity, with
      an IC(50) value of 1.5 microM for ACN and 4.5 microM for the enantiomer.
      Inhibition curves had Hill slopes larger than 1, indicating more than one binding
      site per receptor. Block did not require intracellular compounds containing high
      energy phosphate bonds and was not affected by analogs of GTP, suggesting that
      the mechanism does not require the activation of second messengers. Block did not
      appear to be strongly selective between open and closed channel states or to
      involve changes in desensitization. A comparison of different steroids showed
      that a beta-orientation of groups at the 17 position produced more block than
      alpha-orientated diastereomers. The stereochemistry at the 3 and 5 positions was
      less influential for block of alpha4beta2 nicotinic receptors, despite its
      importance for potentiation of gamma-aminobutyric acid(A) receptors. The ability
      of steroids to block neuronal nicotinic receptors correlated with their ability
      to produce anesthesia in Xenopus tadpoles, but the concentrations required for
      inhibition are generally greater. Similarly, the concentrations of endogenous
      neurosteroids required to inhibit receptors are larger than estimates of brain
      concentrations.

PMID- 10908303
TI  - Complex involvement of pertussis toxin-sensitive G proteins in the regulation of
      type 1alpha metabotropic glutamate receptor signaling in baby hamster kidney
      cells.
AB  - Previously, we demonstrated that the coupling of the metabotropic glutamate
      receptor mGlu1alpha to phosphoinositide hydrolysis is enhanced by pertussis toxin
      (PTX) in stably transfected baby hamster kidney cells (BHK). Here, we show that
      the PTX effect on agonist-stimulated [(3)H]inositol phosphate accumulation can be
      resolved into two components: an immediate increase in agonist potency, and a
      more slowly developing increase in the magnitude of the response observed at
      maximally effective agonist concentrations. Using G(q/11)alpha- and G(i/o)alpha
      selective antibodies to immunoprecipitate [(35)S]guanosine-5'-O-(3
      thio)triphosphate-bound Galpha proteins, we also show that agonist stimulation of
      mGlu1alpha in BHK membranes increases specific [(35)S]guanosine-5'-O-(3
      thio)triphosphate binding to both G(q/11) and G(i/o) proteins. Preincubation of
      BHK-mGlu1alpha with L-glutamate (300 microM) results in a progressive loss (60%
      in 30 min) of L-quisqualate-induced [(3)H]inositol phosphate accumulation
      (without a change in potency), providing evidence for agonist-induced receptor
      desensitization. Although such desensitization of mGlu receptor signaling was
      mimicked by a phorbol ester, agonist-induced phosphorylation of the receptor was
      not observed and protein kinase C inhibition by Ro 31-8220 did not prevent L
      glutamate-mediated desensitization. In contrast, PTX treatment of the cells
      almost completely prevented L-glutamate-mediated desensitization. Together, these
      data provide evidence for a multifunctional coupling of mGlu1alpha to different
      types of G proteins, including PTX-sensitive G(i)-type G proteins. The latter are
      involved in the negative control of phospholipase C activity while also
      influencing the rate of desensitization of the mGlu1alpha receptor.

PMID- 10908304
TI  - Dexamethasone induces pregnane X receptor and retinoid X receptor-alpha
      expression in human hepatocytes: synergistic increase of CYP3A4 induction by
      pregnane X receptor activators.
AB  - In this report we show that submicromolar concentrations of dexamethasone enhance
      pregnane X receptor (PXR) activator-mediated CYP3A4 gene expression in cultured
      human hepatocytes. Because this result is only observed after 24 h of cotreatment
      and is inhibited by pretreatment with cycloheximide, we further investigated
      which factor(s), induced by dexamethasone, might be responsible for this effect.
      We report that dexamethasone increases both retinoid X receptor-alpha (RXRalpha)
      and PXR mRNA expression in cultured human hepatocytes, whereas PXR activators
      such as rifampicin and clotrimazole do not. Accumulation of RXRalpha and PXR mRNA
      reaches a maximum at a concentration of 100 nM dexamethasone after treatment for
      6 to 12 h and is greatly diminished by RU486. A similar pattern of expression is
      observed with tyrosine aminotransferase mRNA. Moreover, the effect of
      dexamethasone on PXR mRNA accumulation seems to be through direct action on the
      glucocorticoid receptor (GR) because the addition of cycloheximide has no effect,
      and dexamethasone does not affect the degradation of PXR mRNA. Furthermore,
      dexamethasone induces the accumulation of a RXRalpha-immunoreactive protein and
      increases the nuclear level of RXRalpha:PXR heterodimer as shown by gel shift
      assays with a CYP3A4 ER6 PXRE probe. This accumulation of latent PXR and RXRalpha
      in the nucleus of hepatocytes explains the synergistic effect observed with
      dexamethasone and PXR activators together on CYP3A4 induction. These results
      reveal the existence of functional cross talk between the GR and PXR, and may
      explain some controversial aspects of the role of the GR in CYP3A4 induction.

PMID- 10908305
TI  - From agonist to antagonist: Fab fragments of an agonist-like monoclonal anti
      beta(2)-adrenoceptor antibody behave as antagonists.
AB  - We previously demonstrated that the monoclonal antibody Mab6H8 raised against the
      second extracellular loop of the beta(2)-adrenoceptor (beta(2)-AR) had an agonist
      like activity, mediated by the activation of L-type Ca(2+) channels by protein
      kinase A through the adenylyl cyclase pathway. We suggested that this Mab acts by
      stabilizing an active dimeric conformation of the beta(2)-AR. To substantiate
      this hypothesis, we prepared monomeric Fab fragments of Mab6H8. Comparison of the
      physicochemical parameters of antigen interaction with both the Mab and its Fab
      fragments were determined by surface plasmon resonance, showing a 5- to 10-fold
      lower affinity of the fragments compared with the bivalent antibody. We
      determined the biological activity of antibody and Fab fragments in two systems:
      spontaneous beating neonatal rat cardiomyocytes to study the chronotropic effects
      and isolated guinea pig cardiomyocytes to study L-type Ca(2+) channel activation.
      Fab fragments as such had no "agonist-like" effects in both systems but inhibited
      receptor activation with the beta(2)-specific agonist clenbuterol. Addition of a
      cross-linking rabbit anti-mouse IgG restored the agonist-like effect of the Fab
      fragments. These results suggest that Fab fragments induce a conformational
      change in the receptor, inhibiting the accessibility of the pharmacophore pocket
      to clenbuterol. Dimerization of this receptor conformation induces an agonist
      like effect. Antireceptor antibodies can thus act both as agonist in the dimeric
      state and as antagonist in the monomeric state.

PMID- 10908306
TI  - Deletion of individual exons and induction of soluble murine interleukin-5
      receptor-alpha chain expression through antisense oligonucleotide-mediated
      redirection of pre-mRNA splicing.
AB  - Expression of the interleukin-5 receptor-alpha (IL-5Ralpha) chain is thought to
      play an important role in the pathogenesis of asthma and other eosinophilic
      diseases. With antisense oligonucleotides (ASOs) chemically modified to provide
      increased hybridization affinity for RNA but that do not support RNase H-mediated
      cleavage (2'-O-methoxyethyl-modified ASOs), we show that constitutive splicing of
      murine IL-5Ralpha mRNA can be modulated in cells such that individual exons may
      be selectively deleted from mature transcripts. Specific deletion of individual
      exons and redirection of alternative splicing of the IL-5Ralpha mRNA have been
      achieved with this approach, by targeting 3'-splice sites or exon sequences
      immediately downstream of an alternative splice site. ASO targeting with these
      strategies resulted in inhibition of mRNA and protein levels of the membrane IL
      5Ralpha isoform capable of signaling IL-5-mediated growth and antiapoptotic
      signals to eosinophils. Membrane isoform IL-5Ralpha inhibition was coupled with
      an increase in expression of mRNA for the alternatively spliced soluble isoform,
      which binds IL-5 extracellularly and may block its function. These observations
      suggest the potential general therapeutic use of an antisense approach to
      increase expression of variant RNA transcripts and to thereby produce proteins
      devoid of specific functional domains that may impact disease processes, as well
      as its specific utility for modulating expression of a key cytokine receptor
      implicated in allergic inflammation.

PMID- 10908307
TI  - Receptor density and recycling affect the rate of agonist-induced desensitization
      of mu-opioid receptor.
AB  - Previously, we reported that the time course for the rapid phosphorylation rate
      of mu-opioid receptor expressed in human embryonic kidney (HEK)293 cells did not
      correlate with the slow receptor desensitization rate induced by [D-Ala(2),N
      MePhe(4), Gly-ol(5)]-enkephalin (DAMGO). However, others have suggested that
      receptor phosphorylation is the trigger for mu-opioid receptor desensitization.
      In this study, we demonstrated the relatively slow rate of receptor
      desensitization could be attributed partially to the recycling of internalized
      receptor as determined by fluorescence-activated cell-sorting analysis. However,
      the blockade of the endocytic and Golgi transport events in HEK293 cells with
      monensin and brefeldin A did not increase the initial rate of receptor
      desensitization. But the desensitization rate was increased by reduction of the
      mu-opioid receptor level with beta-furnaltrexamine (betaFNA). The reduction of
      the receptor level with 1 microM betaFNA significantly increased the rate of
      etorphine-induced receptor desensitization. By blocking the ability of receptor
      to internalize with 0.4 M sucrose, a significant degree of receptor being rapidly
      desensitized was observed in HEK293 cells pretreated with betaFNA. Hence, mu
      opioid receptor is being resensitized during chronic agonist treatment. The
      significance of resensitization of the internalized receptor in affecting
      receptor desensitization was demonstrated further with human neuroblastoma SHSY5Y
      cells that expressed a low level of mu-opioid receptor. Although DAMGO could not
      induce a rapid desensitization in these cells, in the presence of monensin and
      brefeldin A, DAMGO desensitized the mu-opioid receptor's ability to regulate
      adenylyl cyclase with a t(1/2) = 9.9 +/- 2.1 min and a maximal desensitized level
      at 70 +/- 4.7%. Furthermore, blockade of receptor internalization with 0.4 M
      sucrose enhanced the DAMGO-induced receptor desensitization, and the inclusion of
      monensin prevented the resensitization of the mu-opioid receptor after chronic
      agonist treatment in SHSY5Y cells. Thus, the ability of the mu-opioid receptor to
      resensitize and to recycle, and the relative efficiency of the receptor to
      regulate adenylyl cyclase activity, contributed to the observed slow rate of mu
      opioid receptor desensitization in HEK293 cells.

PMID- 10908308
TI  - CCK-B/Gastrin receptor transmembrane domain mutations selectively alter synthetic
      agonist efficacy without affecting the activity of endogenous peptides.
AB  - Recent efforts have focused on identifying small nonpeptide molecules that can
      mimic the activity of endogenous peptide hormones. Understanding the molecular
      basis of ligand-induced receptor activation by these divergent classes of ligands
      should expedite the process of drug development. Using the cholecystokinin
      B/gastrin receptor (CCK-BR) as a model system, we have recently shown that both
      affinity and efficacy of nonpeptide ligands are markedly affected by amino acid
      alterations within a putative transmembrane domain (TMD) ligand pocket. In this
      report, we examine whether residues projecting into the TMD pocket determine the
      pharmacologic properties of structurally diverse CCK-BR ligands, including
      peptides and synthetic peptide-derived partial agonists (peptoids). Nineteen
      mutant human CCK-BRs, each including a single TMD amino acid substitution, were
      transiently expressed in COS-7 cells and characterized. Binding affinities as
      well as ligand-induced inositol phosphate production at the mutant CCK-BRs were
      assessed for peptides (CCK-8 and CCK-4) and for peptoids (PD-135,158 and PD-136,
      450). Distinct as well as overlapping determinants of peptide and peptoid binding
      affinity were identified, supporting that both classes of ligands, at least in
      part, interact with the CCK-BR TMD ligand pocket. Eight point mutations resulted
      in marked increases or decreases in the functional activity of the synthetic
      peptoid ligands. In contrast, the functional activity of both peptides, CCK-8 and
      CCK-4, was not affected by any of the CCK-BR mutations. These findings suggest
      that the mechanisms underlying activation of G-protein-coupled receptors by
      endogenous peptide hormones versus synthetic ligands may markedly differ.

PMID- 10908310
TI  - The platelet-derived growth factor receptor stimulation of p42/p44 mitogen
      activated protein kinase in airway smooth muscle involves a G-protein-mediated
      tyrosine phosphorylation of Gab1.
AB  - Using cultured airway smooth muscle cells, we showed previously that the platelet
      derived growth factor (PDGF) receptor uses the G-protein, G(i), to stimulate Grb
      2-associated phosphoinositide 3-kinase (PI3K) activity. We also showed that this
      was an intermediate step in the activation of p42/p44 mitogen-activated protein
      kinase (p42/p44 MAPK) by PDGF. We now present two lines of evidence that provide
      further support for this model. First, we report that PDGF stimulates the G(i)
      mediated tyrosine phosphorylation of the Grb-2 adaptor protein, Gab1. This
      phosphorylation appears to be necessary for association of PI3K1a with the Gab1
      Grb-2 complex. Second, PI3K appears to promote the subsequent association of
      dynamin II (which is involved in clathrin-mediated endocytic processing) with the
      complex. Furthermore, inhibitors of PI3K and clathrin-mediated endocytosis
      reduced the PDGF-dependent activation of p42/p44 MAPK, suggesting a role for PI3K
      in the endocytic signaling process leading to stimulation of p42/p44 MAPK.
      Together, these results begin to define a common signaling model for certain
      growth factor receptors (e.g., PDGF, insulin, insulin-like growth factor-1, and
      fibroblast growth factor) which use G(i) to transmit signals to p42/p44 MAPK.

PMID- 10908309
TI  - Edg2 receptor functionality: gialpha1 coexpression and fusion protein studies.
AB  - Recombinant receptor cell lines are widely used in G-protein-coupled receptor
      selectivity studies. To unequivocally interpret the results of such studies, it
      is essential that the host cell line does not endogenously express the receptor
      of interest and in addition is unresponsive to the receptor's natural ligand.
      Here we describe an approach to overcome such difficulties associated with orphan
      receptors or, as in the present case, receptors whose endogenous ligand
      ubiquitously affects mammalian cells. The functional heterologous assay system
      described is for the hEdg2 receptor, which uses lysophosphatidic acid as its
      endogenous ligand. Once activated, this receptor mediates its effects via
      multiple secondary messenger pathways, including a Gi-coupled pathway. We have
      transiently expressed a pertussis toxin-insensitive hEdg2 receptor-ratGialpha1
      fusion protein into human embryonic kidney cells and have monitored the ability
      of compounds to stimulate [(35)S]GTPgammaS binding in membranes prepared from
      these cells after pretreatment with toxin. Because the assay conditions used
      favor Gi-mediated responses and because endogenous Gialpha subunits are rendered
      inactive, the response measured is, by definition, fusion protein-mediated.
      Consequently, we have developed an assay that monitors definitively Edg2 receptor
      mediated responses in a mammalian cell line. A limited structure activity
      relationship study suggests that the lysophospholipid carbon chain has a role in
      receptor activation and in addition indicates that certain modifications to the
      phosphate group are tolerated.

PMID- 10908311
TI  - Kinetic analysis of agonist-induced down-regulation of the beta(2)-adrenergic
      receptor in BEAS-2B cells reveals high- and low-affinity components.
AB  - We examined the interrelationships of internalization and down-regulation of the
      beta(2)-adrenergic receptor in response to treatment of the BEAS-2B human
      epithelial cell line with both a series of agonists at high occupancy and with
      various concentrations of fenoterol that gave occupancies from 0.93 to 0.001. We
      found that the extent of internalization measured after a 30-min treatment
      increased as a function of coupling efficiency, with ephedrine, dobutamine,
      albuterol, fenoterol, and epinephrine giving 0, 7, 17, 48, and 55%
      internalization, respectively. With the exception of dobutamine, the rates of
      down-regulation (k(deg)) also showed a dependence on agonist coupling efficiency,
      giving (in terms of fraction of receptors lost/h) 0.082 with ephedrine, 0.250
      with dobutamine, 0.148 with albuterol, 0.194 with fenoterol, and 0.212 with
      epinephrine. Comparison of down-regulation to internalization showed that weak
      agonists caused down-regulation in the absence of significant internalization.
      The extent of internalization caused by fenoterol over a 1000-fold range of
      occupancy was proportional to agonist occupancy. However, although no
      internalization was observed with the low concentrations (0.2 and 2 nM
      fenoterol), these concentrations did cause significant down-regulation. Thus, as
      with partial agonists, it was clear that down-regulation occurred in the absence
      of measurable internalization. The kinetics of agonist-induced down-regulation
      are consistent with a scheme in which down-regulation proceeds by two pathways; a
      high-affinity, low-capacity component (EC(50) = 0.5 nM) clearly dissociated from
      internalization and a low-affinity, high-capacity component (EC(50) = 160 nM)
      closely correlated with internalization.

PMID- 10908312
TI  - Molecular mechanisms of butylated hydroxylanisole-induced toxicity: induction of
      apoptosis through direct release of cytochrome c.
AB  - Butylated hydroxyanisole (BHA), a commonly used food preservative, is reported to
      have anticarcinogenic properties in some animal models. However, the use of BHA
      as a chemopreventive agent against cancer in human has been challenged by the
      observation that BHA may exert toxic effect in some tissues of animals.
      Therefore, it is of great significance to understand the mechanism of BHA-induced
      toxicity. Here, we report that BHA induces apoptosis in freshly isolated rat
      hepatocytes. Treatment of hepatocytes with BHA also induced loss of mitochondrial
      transmembrane potential (Deltapsi(m)), cytochrome c, and activation of caspase-3,
      -8, and -9 but not caspase-1. Pretreatment with cyclosporin A, an agent that
      stabilizes mitochondrial permeability transition pore, inhibited BHA-induced loss
      of Deltapsi(m), cytochrome c release, caspase activation, and apoptosis.
      Interestingly, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone failed to
      prevent these mitochondrial events, although it blocked caspase activation and
      apoptosis. Furthermore, BHA-induced apoptosis appeared to be independent of
      formation of reactive intermediates, as evidenced by the lack of effects of
      antioxidants N-acetyl-L-cysteine and ascorbic acid. Indeed, direct incubation of
      BHA with isolated mitochondria triggered cytochrome c release. Thus, these
      results indicate that the cytotoxicity of BHA is due to the induction of
      apoptosis that is mediated by the direct release of cytochrome c and the
      subsequent activation of caspases.

PMID- 10908313
TI  - Resolution of inverse agonist-induced up-regulation from constitutive activity of
      mutants of the alpha(1b)-adrenoceptor.
AB  - Constitutively active forms of the hamster alpha(1b)-adrenoceptor can be produced
      from the point mutations Asp(142)Ala or Ala(293)Glu or exchange of a small
      segment of the third intracellular loop with the equivalent region of the beta(2)
      adrenoceptor. Green fluorescent protein (GFP)-tagged forms of each of these
      mutants and of the wild type alpha(1b)-adrenoceptor were expressed stably in
      HEK293 cells. The wild type alpha(1b)-adrenoceptor-GFP was expressed both at the
      plasma membrane and with a distinctly perinuclear punctate pattern. Sustained
      treatment with a range of antagonist/inverse agonist ligands failed to modulate
      the cellular distribution or levels of expression of this construct. The form of
      the alpha(1b)-adrenoceptor containing the beta(2)-adrenoceptor sequence
      substitution was predominantly located in punctate intracellular vesicles and
      sustained challenge with the same series of antagonists/inverse agonists produced
      a 5-fold up-regulation of protein levels with elevation of both plasma membrane
      and intracellular receptor. Quantification of these effects could be produced by
      spectrofluorometric analysis of cells grown in a 96-well microtiter plate. In
      contrast, both the Asp(142)Ala and Ala(293)Glu forms of the alpha(1b)
      adrenoceptor-GFP were located predominantly at the plasma membrane. Levels of
      these two point mutants were not increased by any of the antagonist/inverse
      agonist ligands tested, although the sequence substitution mutation encompasses
      codon 293. Resolution of constitutive activity and ligand-induced up-regulation
      was further exemplified by a mutant lacking eight serine residues in the C
      terminal tail that displayed little constitutive activity but was up-regulated by
      sustained ligand challenge. These results demonstrate the nonequivalence of
      mutations in their regulation by antagonist/inverse agonist ligands.

PMID- 10908314
TI  - Evidence for Edg-3 receptor-mediated activation of I(K.ACh) by sphingosine-1
      phosphate in human atrial cardiomyocytes.
AB  - Sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPPC) have been
      reported to activate muscarinic receptor-activated inward rectifier K(+) current
      (I(K.ACh)) in cultured guinea pig atrial myocytes with similar nanomolar potency.
      Members of the endothelial differentiation gene (Edg) receptor family were
      recently identified as receptors for SPP; however, these receptors respond only
      to micromolar concentrations of SPPC. Here we investigated the sphingolipid
      induced activation of I(K.ACh) in freshly isolated guinea pig, mouse, and human
      atrial myocytes. SPP activated I(K.ACh) in atrial myocytes from all three species
      with a similar nanomolar potency (EC(50) values: 4-8 nM). At these low
      concentrations, SPPC also activated I(K.ACh) in guinea pig myocytes. In contrast,
      SPPC was almost ineffective in mouse and human myocytes, thus resembling the
      pharmacology of the Edg receptors. Transcripts of Edg-1, Edg-3, and Edg-5 were
      detected in human atrial cells. Moreover, activation of I(K.ACh) by SPP was
      blocked by the Edg-3-selective antagonist suramin, which did not affect basal or
      carbachol-stimulated K(+) currents. In conclusion, these data indicate that
      I(K.ACh) activation by SPP and SPPC exhibits large species differences.
      Furthermore, they suggest that SPP-induced I(K.ACh) activation in human atrial
      myocytes is mediated by the Edg-3 subtype of SPP receptors.

PMID- 10908315
TI  - The D2s dopamine receptor stimulates phospholipase D activity: a novel signaling
      pathway for dopamine.
AB  - The D2 dopamine receptor isoforms signal to a variety of cellular effectors in
      both the central nervous system and periphery. Two alternative splice forms of
      the D2 dopamine receptor exist, the D2s (short) and D2l (long), which has an
      insertion of 29 amino acids in the third intracellular loop (). In cells of the
      anterior lobe of the pituitary, D2 dopamine receptors (both forms) are present on
      lactotroph cells coupled to the inhibition of adenylyl cyclase, activation of
      voltage-gated calcium channels, and inhibition of potassium channels. We describe
      here a novel signaling pathway for the D2s, which is the activation of
      phospholipase D (PLD). GH4C1 cells, a clonal line derived from a rat pituitary
      tumor, were stably transfected with the gene encoding the D2s, generating GH4-121
      cells. Treatment of GH4-121 cells with a dopaminergic agonist resulted in
      activation of PLD in both a dose-dependent and time-dependent manner. This
      signaling pathway was not inhibited by prior treatment of cells with pertussis
      toxin at concentrations that ablate other D2s receptor signaling in this cell
      line. The stimulation of PLD activity by D2s appeared to correlate with the
      presence of a specific protein kinase C isoform, PKCepsilon. The D2s stimulation
      of PLD activity was blocked by preincubation of cells with C3 exoenzyme,
      indicating that the stimulation of PLD may involve Rho family members. The
      stimulation of PLD by dopaminergic agonists took place in the absence of any
      detectable stimulation of phosphoinositide metabolism.

PMID- 10908316
TI  - The mouse L-histidine decarboxylase gene: structure and transcriptional
      regulation by CpG methylation in the promoter region.
AB  - To investigate the regulation of mouse L-histidine decarboxylase (HDC) gene
      expression, we isolated genomic DNA clones encoding HDC. Structural analysis
      revealed that the mouse HDC gene was composed of 12 exons, spanning approximately
      24 kb. Northern blotting analysis indicated that, among the cell lines examined,
      a high level of HDC gene expression was restricted to mature mast cell lines and
      an erythroblastic cell line. The gene was induced strongly in the mouse immature
      mast cell line P815 after incubation in the peritoneal cavity of BDF1 mice. We
      observed that the promoter region was demethylated in the HDC-expressing cell
      lines and in induced P815 cells. Interestingly, forced demethylation by 5
      azacytidine (5-azaC) treatment induced high expression of HDC mRNA in P815 cells.
      The activity of a mouse HDC promoter-reporter construct stably transfected in
      P815 cells was repressed by in vitro patch-methylation. This low promoter
      activity of the patch-methylated reporter construct was restored after 5-azaC
      treatment, which demethylated the patch-methylated promoter. These results
      indicate that DNA methylation state of the promoter region controls HDC gene
      expression.

PMID- 10908317
TI  - The analysis of chimeric human/rainbow trout estrogen receptors reveals amino
      acid residues outside of P- and D-boxes important for the transactivation
      function.
AB  - The amino acid sequence of rainbow trout estrogen receptor (rtER) is highly
      conserved in the C domain but presents few similarities in the A/B and E domains
      with human estrogen receptor alpha (hER) [NR3A1]. A previous study has shown that
      rtER and hER have differential functional activities in yeast Saccharomyces
      cerevisiae. To determine the domain(s) responsible for these differences,
      chimeric human/rainbow trout estrogen receptors were constructed. The A/B, C/D or
      E/F regions of rtER were replaced by corresponding regions of hER and expressed
      in yeast cells. Ligand-binding and transcription activation abilities of these
      hybrid receptors were compared with those of wild-type rtER or hER. Surprisingly,
      our data revealed that the human C/D domains play an important role in the
      magnitude of transactivation of ER. Two other chimeric ERs carrying either a C or
      D domain of hER showed that the C domain was responsible for this effect whereas
      the D domain did not affect hybrid receptor activities. Moreover, a chimeric hER
      carrying the C domain of rtER showed maximal transcriptional activity similar to
      that observed with rtER. Gel shift assays showed that, whereas rtER and hER
      present a similar binding affinity to an estrogen response element (ERE) element,
      the rtER C domain is responsible for a weaker DNA binding stability compared to
      those of hER. In addition, the human C domain allows approximately 2 times faster
      association of ER to an ERE. Utilization of reporter genes containing one or
      three EREs confirms that rtER requires protein-protein interactions for its
      stabilization on DNA and that the C domain is involved in this stabilization.
      Moreover, AF-1 may be implicated in this synergistic effect of EREs.
      Interestingly, although E domains of these two receptors are much less conserved,
      replacement of this domain in rtER by its human counterpart resulted in higher
      estradiol sensitivity but no increase in the magnitude of transactivation. Data
      from the chimeric receptors, rtER(hC) and hER(rtC), demonstrated that rtER AF-1
      and AF-2 activation domains activated transcription in the presence of estradiol
      similar to both AF-1 and AF-2 hER. This implies that these domains, which show
      poor sequence homology, may interact with similar basal transcription factors.

PMID- 10908318
TI  - Common fold in helix-hairpin-helix proteins.
AB  - Helix-hairpin-helix (HhH) is a widespread motif involved in non-sequence-specific
      DNA binding. The majority of HhH motifs function as DNA-binding modules, however,
      some of them are used to mediate protein-protein interactions or have acquired
      enzymatic activity by incorporating catalytic residues (DNA glycosylases). From
      sequence and structural analysis of HhH-containing proteins we conclude that most
      HhH motifs are integrated as a part of a five-helical domain, termed (HhH)(2)
      domain here. It typically consists of two consecutive HhH motifs that are linked
      by a connector helix and displays pseudo-2-fold symmetry. (HhH)(2) domains show
      clear structural integrity and a conserved hydrophobic core composed of seven
      residues, one residue from each alpha-helix and each hairpin, and deserves
      recognition as a distinct protein fold. In addition to known HhH in the
      structures of RuvA, RadA, MutY and DNA-polymerases, we have detected new HhH
      motifs in sterile alpha motif and barrier-to-autointegration factor domains, the
      alpha-subunit of Escherichia coli RNA-polymerase, DNA-helicase PcrA and DNA
      glycosylases. Statistically significant sequence similarity of HhH motifs and
      pronounced structural conservation argue for homology between (HhH)(2) domains in
      different protein families. Our analysis helps to clarify how non-symmetric
      protein motifs bind to the double helix of DNA through the formation of a pseudo
      2-fold symmetric (HhH)(2) functional unit.

PMID- 10908320
TI  - Resolution of a Holliday junction by vaccinia topoisomerase requires a spacer DNA
      segment 3' of the CCCTT/ cleavage sites.
AB  - Vaccinia virus DNA topoisomerase catalyzes resolution of synthetic Holliday
      junctions in vitro. The mechanism entails concerted transesterifications at two
      recognition sites, 5'-CCCTT/, that are opposed within a partially mobile four-way
      junction. Efficient resolution occurs on a junction with a 10 bp segment of
      branch mobility (5'-GCCCTTATCG) that extends 4 bp 3' of the scissile phosphate.
      Here we report that resolution is decreased when branch mobility is limited to an
      8 bp segment extending 2 bp 3' of the cleavage site and then eliminated when
      branch mobility is confined to the 6 bp GCCCTT sequence 5' of the scissile
      phosphate. We surmise that a spacer region 3' of CCCTT is needed for simultaneous
      cleavage at two opposing sites at the junction. Branch mobility is not required
      for reaction chemistry at a junction, because topoisomerase cleaves a single
      CCCTT site in a non-mobile four-way junction where the scissile phosphate is at
      the crossover point. The junction resolvase activity of topo-isomerase may be
      involved in forming the hairpin telomeres of the vaccinia genome.

PMID- 10908319
TI  - Transcriptional activation by LR1 at the Emu enhancer and switch region sites.
AB  - LR1 is a B cell-specific, sequence-specific duplex DNA binding activity which is
      induced in B cells carrying out class switch recombination. Here we identify
      several properties of LR1 which enable it to function in transcriptional
      regulation. We show that LR1 contributes to transcriptional activation by the Emu
      immunoglobulin heavy chain intron enhancer by binding to a site within the
      enhancer core. We further show that LR1 bends DNA upon binding. In addition, we
      show that LR1 is itself a bona fide transcriptional activator, as multimerized
      LR1 sites produce an element which can enhance transcription from a minimal
      promoter. In order for class switch recombination to occur, an activating signal
      must be transmitted via the Emu core, and both S regions targeted for
      recombination must be actively transcribed. The properties of LR1 that we have
      identified suggest distinct potential functions of LR1 duplex DNA binding
      activity in class switch recombination. First, LR1 may contribute to
      recombinational activation by the Emu core. Second, there are multiple potential
      LR1 duplex binding sites in each of the G-rich switch regions, and LR1 bound at
      contiguous sites may enhance recombination by stimulating transcription of the S
      regions.

PMID- 10908321
TI  - Precise arrangement of factor-binding sites is required for murine CD4 promoter
      function.
AB  - The control of CD4 expression is linked to the signaling events that mediate T
      cell development and is directly dependent on the CD4 promoter. The CD4 promoter
      does not contain functionally redundant sites: all four factor-binding sites must
      be intact to achieve wild-type activity. Here we demonstrate that the precise
      position of three factor-binding sites relative to each other is essential for
      promoter activity, indicating that they function together as an inseparable
      cassette for assembly of the transcription initiation complex. Small changes in
      either phasing or distance between any two sites in this cassette leads to
      complete abrogation of promoter function. In addition, we demonstrate that one of
      the factors that bind the promoter cassette is not present in CD8 SP T(C) cells.
      Thus, this factor is a candidate for mediating the relative subclass specificity
      of CD4 promoter function in activated CD4 SP T(H) cells.

PMID- 10908322
TI  - Effect of single mutations in the OGG1 gene found in human tumors on the
      substrate specificity of the Ogg1 protein.
AB  - We have investigated the effect of single amino acid substitutions of conserved
      arginines on the catalytic activities of the human Ogg1 protein (alpha-hOgg1
      Ser(326)) (wild-type alpha-hOgg1). Mutant forms of hOgg1 with mutations Arg(46)-
      >Gln (alpha-hOgg1-Gln(46)) and Arg(154)-->His (alpha-hOgg1-His(154)) have
      previously been identified in human tumors. The mutant proteins alpha-hOgg1
      Gln(46) and alpha-hOgg1-His(154) were expressed in Escherichia coli and purified
      to homogeneity. The substrate specificities of these proteins and wild-type alpha
      hOgg1 were investigated using gamma-irradiated DNA and the technique of gas
      chromatography/isotope-dilution mass spectrometry. All three enzymes excised 2,6
      diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) and 8-hydroxyguanine (8-OH-Gua)
      from gamma-irradiated DNA containing a multiplicity of base lesions. Michaelis
      Menten kinetics of excision were measured. Significant differences between
      excision kinetics of these three enzymes were observed. Excision of FapyGua and 8
      OH-Gua by wild-type alpha-hOgg1 was greater than that by alpha-hOgg1-Gln(46) and
      alpha-hOgg1-His(154). The latter mutant protein was less active than the former.
      The diminished activity of the mutant proteins was more pronounced for 8-OH-Gua
      than for FapyGua. Cleavage assays were also performed using (32)P-labeled 34mer
      oligonucleotide duplexes containing a single 8-OH-Gua paired to each of the four
      DNA bases. The results obtained with the oligonucleotide containing the 8-OH
      Gua/Cyt pair were in good agreement with those observed with gamma-irradiated
      DNA. Wild-type alpha-hOgg1 and its mutants repaired the three mismatches less
      efficiently than the 8-OH-Gua/Cyt pair. The substitution of Arg(154), in addition
      to diminishing the activity on 8-OH-Gua, relaxes the selectivity found in the
      wild-type alpha-hOgg1 for the base opposite 8-OH-Gua. Taken together the results
      show that the mutant forms alpha-hOgg1-Gln(46) and alpha-hOgg1-His(154) found in
      human tumors are defective in their catalytic capacities.

PMID- 10908323
TI  - Structural analysis of new local features in SECIS RNA hairpins.
AB  - Decoding of the UGA selenocysteine codon for selenoprotein translation requires
      the SECIS element, a stem-loop motif in the 3'-UTR of the mRNA carrying short or
      large apical loops. In previous structural studies, we derived a secondary
      structure model for SECIS RNAs with short apical loops. Work from others proposed
      that intra-apical loop base pairing can occur in those SECIS that possess large
      apical loops, yielding form 2 SECIS versus the form 1 with short loops. In this
      work, SECIS elements arising from eight different selenoprotein mRNAs were
      assayed by enzymatic and/or chemical probing showing that seven can adopt form 2.
      Further, database searches led to the discovery in drosophila and zebrafish of
      SECIS elements in the selenophosphate synthetase 2, type 1 deiodinase and SelW
      mRNAs. Alignment of SECIS sequences not only highlighted the predominance of form
      2 but also made it possible to classify the SECIS elements according to the type
      of selenoprotein mRNA they belong to. Interestingly, the alignment revealed that
      an unpaired adenine, previously thought to be invariant, is replaced by a guanine
      in four SECIS elements. Tested in vivo, neither the A to G nor the A to U changes
      at this position greatly affected the activity while the most detrimental effect
      was provided by a C. The putative contribution of the various SECIS motifs to
      function and ligand binding is discussed.

PMID- 10908324
TI  - Telomerase-dependent repeat divergence at the 3' ends of yeast telomeres.
AB  - Yeast telomeres consist of approximately 300 nt of degenerate repeats with the
      consensus sequence G(2-3)(TG)(1-6). We developed a method for the amplification
      of a genetically marked telomere by PCR, allowing precise length and sequence
      determination of the G-rich strand including the 3' terminus. We examined wild
      type cells, telomerase RNA deficient cells and a strain deleted for YKU70, which
      encodes for a protein involved in telomere maintenance and DNA double strand
      break repair. The 3' end of the G-rich strand was found to be at a variable
      position within the telomeric repeat. No preference for either thymine or guanine
      as the 3' base was detected. Comparison of telomere sequences from clonal
      populations revealed that telomeres consist of a centromere-proximal region of
      stable sequence and a distal region with differing degenerate repeats. In wild
      type as well as yku70-Delta cells, variation in the degenerate telomeric repeats
      was detected starting 40-100 nt from the 3' end. Sequence divergence was
      abolished after deletion of the telomerase RNA gene. Thus, this region defines
      the domain where telomere shortening and telomerase-mediated extension occurs.
      Since this domain is much larger than the number of nucleo-tides lost per
      generation in the absence of telomerase, we propose that telomerase does not
      extend a given telomere in every cell cycle.

PMID- 10908325
TI  - The identification of an endonuclease that cleaves within an HuR binding site in
      mRNA.
AB  - Messenger RNAs (mRNAs) that contain U-rich elements are targeted for rapid decay.
      Selective inhibition of this decay results in a rapid increase in steady state
      level. Thus, this is an important regulatory step in gene expression. Previously,
      we have found that these mRNAs are selectively stabilized by a specific mRNA
      binding protein called HuR. The mechanism of action of HuR is not well
      understood. It has been postulated that HuR stabilizes mRNA by the displacement
      or inhibition of factors that specifically cleave or deadenyl-ate these mRNAs. In
      this paper, we report the identification and characterization of a novel endo
      nuclease that cleaves within an HuR binding site in p27kip1 mRNA. The specificity
      of this endonuclease and its inhibition by HuR argue for it playing a role in the
      postranscriptional regulation of gene expression.

PMID- 10908326
TI  - Oligodeoxynucleotides containing conformationally constrained abasic sites: a UV
      and fluorescence spectroscopic investigation on duplex stability and structure.
AB  - The synthesis and incorporation into oligodeoxy-nucleotides of two novel,
      conformationally restricted abasic (AB) site analogs are described. The stability
      of oligonucleotide 18mer duplexes containing one such AB site opposite any of the
      four natural DNA bases was investigated by UV melting curve analysis and compared
      to that of duplexes containing a conformationally flexible propanediol unit 1 or
      a tetrahydrofuran unit 2 as an AB site analog. No major differences in the
      melting temperatures (DeltaT(m) 0-3 degrees C) between the different abasic
      duplexes were observed. All AB duplexes were found to have T(m)s that were lower
      by 9-15 degrees C relative to a fully matched 18mer control duplex, and by 4-10
      degrees C relative to the corresponding 19mer duplexes in which the AB site is
      replaced by a mismatched nucleobase. Thus we conclude that the loss of stability
      of a duplex that is encountered by removal of a nucleobase from the stack cannot
      be compensated with conformational restriction of the AB site. From the van't
      Hoff transition enthalpies obtained from the melting curves, it appears that
      melting cooperativity is higher for the duplexes containing the conformationally
      rigid AB sites. Fluorescence quenching experiments with duplexes containing the
      fluorescent base 2-amino-purine (2AP) opposite the AB sites showed a weak
      tendency towards more efficient stacking of this base in duplexes containing the
      conformationally constrained AB sites. Thus, such AB sites may structurally
      stabilize the cavity formed by the removal of a base. Potential applications
      emerging from the properties of such conformationally constrained AB sites in DNA
      diagnostics are discussed.

PMID- 10908327
TI  - Dmc1 of Schizosaccharomyces pombe plays a role in meiotic recombination.
AB  - We report here a Schizosaccharomyces pombe gene (dmc1(+)) that resembles budding
      yeast DMC1 in the region immediately upstream of the rad24(+) gene. We showed by
      northern and Southern blot analysis that dmc1(+) and rad24(+) are co-transcribed
      as a bicistronic mRNA of 2.8 kb with meiotic specificity, whereas rad24(+) itself
      is constitutively transcribed as a 1.0-kb mRNA species during meiosis. Induction
      of the bicistronic transcript is under the control of a meiosis-specific
      transcription factor, Ste11. Disruption of both dmc1(+) and rad24(+) had no
      effect on mitosis or spore formation, and dmc1Delta cells displayed no change in
      sensitivity to UV or gamma irradiation relative to the wild type. Tetrad analysis
      indicated that Dmc1 is involved in meiotic recombination. Analysis of gene
      conversion frequencies using single and double mutants of dmc1 and rhp51
      indicated that both Dmc1 and Rhp51 function in meiotic gene conversion. These
      observations, together with a high level of sequence identity, indicate that the
      dmc1(+) gene of S. POMBE: is a structural homolog of budding yeast DMC1, sharing
      both similar and distinct functions in meiosis.

PMID- 10908328
TI  - Modulation of plasma protein binding and in vivo liver cell uptake of
      phosphorothioate oligodeoxynucleotides by cholesterol conjugation.
AB  - Several studies have shown improved efficacy of cholesteryl-conjugated
      phosphorothioate antisense oligodeoxynucleotides. To gain insight into the
      mechanisms of the improved efficacy in vivo, we investigated the disposition of
      ISIS-9388, the 3'-cholesterol analog of the ICAM-1-specific phosphorothioate
      oligodeoxynucleotide ISIS-3082, in rats. Intravenously injected [(3)H]ISIS-9388
      was cleared from the circulation with a half-life of 49.9 +/- 2.2 min (ISIS-3082,
      23.3 +/- 3.8 min). At 3 h after injection, the liver contained 63.7 +/- 3. 3% of
      the dose. Compared to ISIS-3082, the hepatic uptake of ISIS-9388 is approximately
      2-fold higher. Endothelial, Kupffer and parenchymal cells accounted for 45.7 +/-
      5.7, 33.0 +/- 5.9 and 21.3 +/- 2.6% of the liver uptake of [(3)H]ISIS-9388,
      respectively, and intracellular concentrations of approximately 2, 75 and 50
      microM, respectively, could be reached in these cells (1 mg/kg dose).
      Preinjection with polyinosinic acid or poly-adenylic acid reduced the hepatic
      uptake of [(3)H]ISIS-9388, which suggests the involvement of (multiple) scavenger
      receptors. Size exclusion chromatography of mixtures of the oligonucleotides and
      rat plasma indicated that ISIS-9388 binds to a larger extent to high molecular
      weight proteins than ISIS-3082. Analysis by agarose gel electrophoresis indicated
      that ISIS-9388 binds more tightly to plasma proteins than ISIS-3082. The
      different interaction of the oligonucleotides with plasma proteins possibly
      explains their different dispositions. We conclude that cholesterol conjugation
      results in high accumulation of phosphorothioate oligodeoxynucleotides in various
      liver cell types, which is likely to be beneficial for antisense therapy of liver
      associated diseases.

PMID- 10908330
TI  - Human gamma-globin gene promoter element regulates human beta-globin gene
      developmental specificity.
AB  - The persistence of fetal hemoglobin in many patients with deletion type beta
      thalassemias and the expression patterns of human globin genes in transgenic mice
      suggest that gamma- to beta-globin gene switching results primarily from
      competition of gamma- and beta-globin genes for interaction with the beta-globin
      locus control region (LCR). To define regulatory sequences that are essential for
      the competitive advantage of the gamma gene at early developmental stages, stable
      transgenic mouse lines were produced with LCR gamma-beta constructs containing
      deletions of gamma 5'-flanking DNA. All constructs contained the full 22 kb LCR,
      a 4.1 kb beta-globin gene and a gamma-globin gene with 1348, 383, 202, 130, 72 or
      52 bp of 5'-flanking sequence. Primer extension analysis of yolk sac, fetal liver
      and blood RNA from these lines demonstrated that a region between -202 and -130
      of the human gamma-globin gene promoter was required to suppress beta-globin gene
      expression at early developmental stages. Four transcription factor binding sites
      within this region [GATA(p), Oct1, GATA(d) and CACCC] were mutated independently
      in LCR gamma-beta constructs and transgenic mouse lines were produced. Only the
      gamma CACCC box mutation resulted in high levels of beta-globin gene expression
      in early embryos. These results demonstrate that the CACCC box of the human gamma
      globin gene plays a critical role in human beta-globin gene developmental
      specificity. The data also suggest that gamma CACCC box binding factors mediate
      LCR-gamma interactions which normally enhance gamma-globin and suppress beta
      globin gene expression in fetal erythroid cells.

PMID- 10908329
TI  - Discrete promoter elements affect specific properties of RNA polymerase II
      transcription complexes.
AB  - The frequency of transcription initiation at specific RNA polymerase II promoters
      is, in many cases, related to the ability of the promoter to recruit the
      transcription machinery to a specific site. However, there may also be functional
      differences in the properties of assembled transcription complexes that are
      promoter-specific or regulator-dependent and affect their activity. Transcription
      complexes formed on variants of the adenovirus major late (AdML) promoter were
      found to differ in several ways. Mutations in the initiator element increased the
      sarkosyl sensitivity of the rate of elongation and decreased the rate of early
      steps in initiation as revealed by a sarkosyl challenge assay that exploited the
      resistance of RNA synthesis to high concentrations of sarkosyl after formation of
      one or two phospho-diester bonds. Similar, but clearly distinct, effects were
      also observed after deletion of the binding site for upstream stimulatory factor
      from the AdML promoter. In contrast, deletion of binding sites for nuclear factor
      1 and Oct-1, as well as mutations in the recognition sequence for initiation site
      binding protein, were without apparent effect on transcription complexes on
      templates containing the mouse mammary tumor virus promoter.

PMID- 10908331
TI  - PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is
      associated with active chromatin.
AB  - The Pax gene family encodes transcription factors essential for organ and tissue
      development in higher eukaryotes. Pax proteins are modular with an N-terminal DNA
      binding domain, a C-terminal transcription activation domain, and a transcription
      repression domain called the octapeptide. How these domains interact with the
      cellular machinery remains unclear. In this report, we describe the isolation and
      characterization of a novel gene and its encoded protein, PTIP, which binds to
      the activation domain of Pax2 and other Pax proteins. PTIP binds to Pax2 in
      vitro, in the yeast two-hybrid assay and in tissue culture cells. The binding of
      PTIP to Pax2 is inhibited by the octapeptide repression domain. The PTIP protein
      contains five BRCT domains, first identified in BRCA1 and other nuclear proteins
      involved in DNA repair/recombination or cell cycle control. Pax2 and PTIP co
      localize in the cell nucleus to actively expressed chromatin and the nuclear
      matrix fraction. For the first time, these results point to a link between Pax
      transcription factors and active chromatin.

PMID- 10908333
TI  - Selective blockage of the 3'-->5' exonuclease activity of WRN protein by certain
      oxidative modifications and bulky lesions in DNA.
AB  - Individuals with mutations in the WRN gene suffer from Werner syndrome, a disease
      with early onset of many characteristics of normal aging. The WRN protein (WRNp)
      functions in DNA metabolism, as the purified polypeptide has both 3'-->5'
      helicase and 3'-->5' exonuclease activities. In this study, we have further
      characterized WRNp exonuclease activity by examining its ability to degrade
      double-stranded DNA substrates containing abnormal and damaged nucleo-tides. In
      addition, we directly compared the 3'-->5' WRNp exonuclease activity with that of
      exo-nuclease III and the Klenow fragment of DNA polymerase I. Our results
      indicate that the presence of certain abnormal bases (such as uracil and
      hypoxanthine) does not inhibit the exonuclease activity of WRNp, exo-nuclease III
      or Klenow, whereas other DNA modifications, including apurinic sites, 8
      oxoguanine, 8-oxoadenine and cholesterol adducts, inhibit or block WRNp. The
      ability of damaged nucleo-tides to inhibit exonucleolytic digestion differs
      significantly between WRNp, exonuclease III and Klenow, indicating that each
      exonuclease has a distinct mechanism of action. In addition, normal and modified
      DNA substrates are degraded similarly by full-length WRNp and an N-terminal
      fragment of WRNp, indicating that the specificity for this activity lies mostly
      within this region. The biochemical and physiological significance of these
      results is discussed.

PMID- 10908332
TI  - Both V(D)J recombination and radioresistance require DNA-PK kinase activity,
      though minimal levels suffice for V(D)J recombination.
AB  - DNA-dependent protein kinase (DNA-PK) is utilized in both DNA double-strand break
      repair (DSBR) and V(D)J recombination, but the mechanism by which this
      multiprotein complex participates in these processes is unknown. To evaluate the
      importance of DNA-PK-mediated protein phosphorylation in DSBR and V(D)J
      recombination, we assessed the effects of the phosphatidyl inositol 3-kinase
      inhibitor wortmannin on the repair of ionizing radiation-induced DNA double
      strand breaks and V(D)J recombination in the V(D)J recombinase inducible B cell
      line HDR37. Wortmannin radiosensitized HDR37, but had no affect on V(D)J
      recombination despite a marked reduction in DNA-PK activity. On the other hand,
      studies with mammalian expression vectors for wild-type human DNA-PK catalytic
      subunit (DNA-PKcs) and a kinase domain mutant demonstrated that only the kinase
      active form of DNA-PKcs can reconstitute DSBR and V(D)J recombination in a DNA
      PKcs-deficient cell line (Sf19), implying that DNA-PKcs kinase activity is
      essential for both DSBR and V(D)J recombination. These apparently contradictory
      results were reconciled by analyses of cell lines varying in their expression of
      recombinant wild-type human DNA-PKcs. These studies establish that minimal DNA
      PKcs protein levels are sufficient to support V(D)J recombination, but
      insufficient to confer resistance to ionizing radiation.

PMID- 10908334
TI  - Similarities and differences in the conformation of protein-DNA complexes at the
      U1 and U6 snRNA gene promoters.
AB  - Most small nuclear RNAs (snRNAs) are synthesized by RNA polymerase II, but U6
      snRNA is synthesized by RNA polymerase III. In the fruit fly Drosophila
      melanogaster the RNA polymerase specificity of the snRNA genes is determined by a
      few nucleotide differences within the proximal sequence element (PSE), a
      conserved sequence located approximately 40-65 bp upstream of the transcription
      start site. The PSE is essential for transcription of both RNA polymerase II
      transcribed and RNA polymerase III-transcribed snRNA genes and is recognized in
      Drosophila by a multi-subunit protein factor termed DM:PBP. Previous studies that
      employed site-specific protein-DNA photocrosslinking indicated that the
      conformation of the DNA-protein complex is different depending upon whether
      DM:PBP is bound to a U1 or U6 PSE sequence. These conformational differences of
      the complex probably represent an early step in determining the selection of the
      correct RNA polymerase. We have now obtained evidence that DM:PBP modestly bends
      the DNA upon interacting with the PSE and that the direction of DNA bending is
      similar for both the U1 and U6 PSEs. Under the assumption that DM:PBP does not
      significantly twist the DNA, the direction of the bend in both cases is toward
      the face of the DNA helix contacted by the 45 kDa subunit of DM:PBP. Together
      with data from partial proteolysis assays, these results indicate that the
      conformational differences in the complexes of DM:PBP with the U1 and U6 PSEs
      more likely occur at the protein level rather than at the DNA level.

PMID- 10908335
TI  - Requirement for the SRS2 DNA helicase gene in non-homologous end joining in
      yeast.
AB  - Mitotic cells experience double-strand breaks (DSBs) from both exogenous and
      endogenous sources. Since unrepaired DSBs can result in genome rearrangements or
      cell death, cells mobilize multiple pathways to repair the DNA damage. In the
      yeast Saccharomyces cerevisiae, mitotic cells preferentially use a homologous
      recombination repair pathway. However, when no significant homology to the DSB
      ends is available, cells utilize a repair process called non-homologous end
      joining (NHEJ), which can join ends with no homology through resection to uncover
      microhomologies of a few nucleotides. Although components of the homologous
      recombination repair system are also involved in NHEJ, the rejoining does not
      involve all of the homologous recombination repair genes. The SRS2 DNA helicase
      has been shown to be required for DSB repair when the homologous single-stranded
      regions are short. Here it is shown that SRS2 is also required for NHEJ,
      regardless of the cell mating type. Efficient NHEJ of sticky ends requires the
      Ku70 and Ku80 proteins and the silencing genes SIR2, SIR3 and SIR4. However, NHEJ
      of blunt ends, while very inefficient, is not further reduced by mutations in
      YKU70, SIR2, SIR3, SIR4 or SRS2, suggesting that this rejoining process occurs by
      a different mechanism.

PMID- 10908337
TI  - Evolution of biological information.
AB  - How do genetic systems gain information by evolutionary processes? Answering this
      question precisely requires a robust, quantitative measure of information.
      Fortunately, 50 years ago Claude Shannon defined information as a decrease in the
      uncertainty of a receiver. For molecular systems, uncertainty is closely related
      to entropy and hence has clear connections to the Second Law of Thermodynamics.
      These aspects of information theory have allowed the development of a
      straightforward and practical method of measuring information in genetic control
      systems. Here this method is used to observe information gain in the binding
      sites for an artificial 'protein' in a computer simulation of evolution. The
      simulation begins with zero information and, as in naturally occurring genetic
      systems, the information measured in the fully evolved binding sites is close to
      that needed to locate the sites in the genome. The transition is rapid,
      demonstrating that information gain can occur by punctuated equilibrium.

PMID- 10908336
TI  - In Rhizobium leguminosarum, NodD represses its own transcription by competing
      with RNA polymerase for binding sites.
AB  - We isolated RNA polymerase (RNAP) from Rhizobium leguminosarum, the nitrogen
      fixing symbiont of peas and VICIA: Its 91 kDa subunit, which is homologous to
      sigma(70) of Escherichia coli RNAP, is necessary for transcription of the
      regulatory nodD gene, which in the presence of certain flavonoids induces
      transcription of other nod genes that are needed for the early steps of
      infection. We also show that negative autoregulation of nodD was achieved through
      competition between RNAP and NodD for their respective binding sites, which
      largely overlap. Combined with the result that high concentrations of the
      flavonoid inducer naringenin relieved the binding affinity of NodD for its target
      DNA, the way in which the nod genes are activated is discussed.

PMID- 10908338
TI  - The unusual gene organization of Leishmania major chromosome 1 may reflect novel
      transcription processes.
AB  - The complete chromosomal sequence for chromosome 1 from Leishmania major Friedlin
      predicts that this chromosome has 79 protein-coding genes. Surprisingly, the
      first 29 of these genes are encoded in tandem on one strand of DNA, and the
      remaining 50 genes are encoded in tandem on the other. No RNA polymerase
      promoters, centromeric sequences or origins of DNA replication have been
      identified in the DNA sequence. Statistical analyses of the nucleotide content
      reveal striking, non-random, sequence-biases that are correlated with genome
      organization. Analysis of coding regions suggests that novel transcription
      processes in Leishmania may be responsible for the nucleotide bias, which in turn
      affects gene organization in the chromosome. These results also suggest that the
      region between the two units of in-tandem genes is a candidate for an origin of
      DNA replication.

PMID- 10908339
TI  - Recognition of protein coding genes in the yeast genome at better than 95%
      accuracy based on the Z curve.
AB  - The Z curve is a three-dimensional space curve constituting the unique
      representation of a given DNA sequence in the sense that each can be uniquely
      reconstructed from the other. Based on the Z curve, a new protein coding gene
      finding algorithm specific for the yeast genome at better than 95% accuracy has
      been proposed. Six cross-validation tests were performed to confirm the above
      accuracy. Using the new algorithm, the number of protein coding genes in the
      yeast genome is re-estimated. The estimate is based on the assumption that the
      unknown genes have similar statistical properties to the known genes. It is found
      that the number of protein coding genes in the 16 yeast chromosomes is </=5645,
      significantly smaller than the 5800-6000 which is widely accepted, and much
      larger than the 4800 estimated by another group recently. The mitochondrial genes
      were not included into the above estimate. A codingness index called the YZ score
      (YZ OE [0,1]) is proposed to recognize protein coding genes in the yeast genome.
      Among the ORFs annotated in the MIPS (Munich Information Centre for Protein
      Sequences) database, those recognized as non-coding by the present algorithm are
      listed in this paper in detail. The criterion for a coding or non-coding ORF is
      simply decided by YZ > 0.5 or YZ < 0.5, respectively. The YZ scores for all the
      ORFs annotated in the MIPS database have been calculated and are available on
      request by sending e-mail to the corresponding author.

PMID- 10908340
TI  - The GAA*TTC triplet repeat expanded in Friedreich's ataxia impedes transcription
      elongation by T7 RNA polymerase in a length and supercoil dependent manner.
AB  - Large expansions of the trinucleotide repeat GAA*TTC within the first intron of
      the X25 (frataxin) gene cause Friedreich's ataxia, the most common inherited
      ataxia. Expansion leads to reduced levels of frataxin mRNA in affected
      individuals. Here we show that GAA*TTC tracts, in the absence of any other
      frataxin gene sequences, can reduce the amount of GAA-containing transcript
      produced in a defined in vitro transcription system. This effect is due to an
      impediment to elongation that forms in the GAA*TTC tract during transcription, a
      phenomenon that is exacerbated by both superhelical stress and increased tract
      length. On supercoiled templates the major truncations of the GAA-containing
      transcripts occur in the distal (3') end of the GAA repeat. To account for these
      observations we present a model in which an RNA polymerase advancing within a
      long GAA*TTC tract initiates the transient formation of an R*R*Y intramolecular
      DNA triplex. The non-template (GAA) strand folds back creating a loop in the
      template strand, and the polymerase is paused at the distal triplex-duplex
      junction.

PMID- 10908341
TI  - The role of trans-acting factors and DNA-bending in the silencing of human beta
      globin gene expression.
AB  - The molecular mechanisms which govern the develop-mental specificity of human
      beta-globin gene transcription have been studied in K562 cells, a human
      eyrthroleukemia line that expresses minimal beta-globin. Protein-binding analysis
      reveals that the 5' region contains three elements bound by trans-acting factors,
      beta-protein 1 (BP1) and beta-protein 2 (BP2). In vitro mutagenesis of each
      individual element in a beta-globin vector containing chloramphenicol acetyl
      transferase (pCAT) followed by transient transfection into K562 cells increased
      levels of CAT activity 5. 5-fold higher than wild-type (wt) betaCAT, consistent
      with their silencing role. Mutagenesis of all three elements, however, resulted
      in activity significantly lower than wt betaCAT. BP1 and BP2 motifs have
      overlapping binding sites for high mobility group proteins (HMG1+2), DNA-bending
      factors, shown here to extrinsically bend the beta-globin promoter.
      Theoretically, mutations in all beta-protein binding sites could affect the
      binding of HMG1+2 sufficiently to impede DNA-protein and/or protein-protein
      interactions needed to facilitate constitutive gene expression. Placing two turns
      of DNA between BP1 and BP2 motifs also increased expression 3-fold, indicative of
      spatial constraints required for optimal silencing. However, insertion of the
      HMG1+2 DNA-bending motif (also equivalent to two turns) facilitates beta
      silencing by re-establishment of BP1-BP2 proximity. Thus a combination of general
      DNA-bending and specific transcriptional factors appear to be involved in beta
      globin silencing in the embryonic/fetal erythroid stage.

PMID- 10908342
TI  - Mutational analyses of dinucleotide and tetranucleotide microsatellites in
      Escherichia coli: influence of sequence on expansion mutagenesis.
AB  - Mutagenesis at [GT/CA](10), [TC/AG](11) and [TTCC/AAGG](9) microsatellite
      sequences inserted in the herpes simplex virus thymidine kinase (HSV-tk) gene was
      analyzed in isogenic mutL(+) and mutL(-) Escherichia coli. In both strains,
      significantly more expansion than deletion mutations were observed at the
      [TTCC/AAGG](9) motif relative to either dinucleotide motif. As the HSV-tk coding
      sequence contains an endogenous [G/C](7) mononucleotide repeat and approximately
      1000 bp of unique sequence, we were able to compare mutagenesis among various
      sequence motifs. We observed that the relative risk of mutation in E.COLI: is:
      [TTCC/AAGG](9) > [GT/CA](10) approximately [TC/AG](11) > unique approximately
      [G/C](7). The mutation frequency varied 1400-fold in mutL(+) cells between the
      tetranucleotide motif and the mononucleotide motif, but only 50-fold in mutL(-)
      cells. The [G/C](7) sequence was destabilized the greatest and the
      tetranucleotide motif the least by loss of mismatch repair. These results
      demonstrate that the quantitative risk of mutation at various microsatellites
      greatly depends on the DNA sequence composition. We suggest alternative models
      for the production of expansion mutations during lagging strand replication of
      the [TTCC/AAGG](9) microsatellite.

PMID- 10908343
TI  - Accessibility of transcriptionally inactive genes is specifically reduced at
      homeoprotein-DNA binding sites in Drosophila.
AB  - We showed previously that homeoproteins bind to multiple DNA sites throughout the
      length of most genes in Drosophila embryos. Based on a comparison of in vivo and
      in vitro DNA binding specificities, we suggested that homeoprotein binding sites
      on actively transcribed genes are largely accessible, whereas the binding of
      homeoproteins to inactive and poorly transcribed genes may be significantly
      inhibited at most sites, perhaps by chromatin structure. To test this model, we
      have measured the accessibility of restriction enzyme sites in a number of genes
      in isolated nuclei. Surprisingly, our data indicate that there is no difference
      in the overall accessibility of sites for several restriction enzymes on active
      versus inactive genes. However, consistent with our model, restriction enzyme
      recognition sequences that overlap with homeoprotein binding sites are less
      accessible on inactive genes than they are on active genes. We propose that
      transcriptional activation in all animals may involve a localized increase in
      accessibility at the AT-rich regions bound by homeo-proteins and perhaps at a few
      other regions, rather than a generalized effect on all sites throughout a gene.

PMID- 10908345
TI  - Silanized nucleic acids: a general platform for DNA immobilization.
AB  - We have developed a method for simultaneous deposition and covalent cross-linking
      of oligonucleotide or PCR products on unmodified glass surfaces. By covalently
      conjugating an active silyl moiety onto oligonucleotides or cDNA in solutions we
      have generated a new class of modified nucleic acids, namely silanized nucleic
      acids. Such silanized molecules can be immobilized instantly onto glass surfaces
      after manual or automated deposition. This method provides a simple and rapid,
      yet very efficient, solution to the immobilization of prefabricated
      oligonucleotides and DNA for chip production.

PMID- 10908344
TI  - The human RAD18 gene product interacts with HHR6A and HHR6B.
AB  - During DNA replication, lesion bypass is an important cellular response to
      unrepaired damage in the genome. In the yeast Saccharomyces cerevisiae, Rad6 and
      Rad18 are required for both the error-free and error-prone lesion bypass
      mechanisms. Furthermore, Rad6-Rad18 interaction is thought to be critical at an
      early step during lesion bypass in yeast. Two closely related human homologs of
      yeast Rad6 have been identified as HHR6A and HHR6B. Here, we report a full-length
      cDNA coding for the human homolog of yeast Rad18. The human RAD18 gene codes for
      a protein of 484 amino acid residues with a calculated molecular weight of 54 804
      Da, and the gene is localized to chromosome 3 between reference intervals D3S3591
      and D3S1283. Human RAD18 protein (hRAD18) was found to interact with HHR6A and
      HHR6B. When co-expressed in yeast cells, stable hRAD18-HHR6A and hRAD18-HHR6B
      protein complexes were identified and purified to near homogeneity. Thus, through
      interaction and complex formation with HHR6A and HHR6B, RAD18 protein may play an
      important role in lesion bypass mechanisms in humans. Consistent with its role as
      a fundamental lesion bypass protein, the RAD18 gene is ubiquitously expressed in
      various human tissues.

PMID- 10908346
TI  - The genes for small nucleolar RNAs in Trypanosoma brucei are organized in
      clusters and are transcribed as a polycistronic RNA.
AB  - Because the organization of snoRNA genes in vertebrates, plants and yeast is
      diverse, we investigated the organization of snoRNA genes in a distantly related
      organism, Trypanosoma brucei. We have characterized the second example of a
      snoRNA gene cluster that is tandemly repeated in the T.BRUCEI: genome. The genes
      encoding the box C/D snoRNAs TBR12, TBR6, TBR4 and TBR2 make up the cluster. In a
      genomic organization unique to trypanosomes, there are at least four clusters of
      these four snoRNA genes tandemly repeated in the T. BRUCEI: genome. We show for
      the first time that the genes encoding snoRNAs in both this cluster and the SLA
      cluster are transcribed in an unusual way as a polycistronic RNA.

PMID- 10908347
TI  - Identification of sequence motifs in oligonucleotides whose presence is
      correlated with antisense activity.
AB  - Design of antisense oligonucleotides targeting any mRNA can be much more
      efficient when several activity-enhancing motifs are included and activity
      decreasing motifs are avoided. This conclusion was made after statistical
      analysis of data collected from >1000 experiments with phosphorothioate-modified
      oligonucleotides. Highly significant positive correlation between the presence of
      motifs CCAC, TCCC, ACTC, GCCA and CTCT in the oligonucleotide and its antisense
      efficiency was demonstrated. In addition, negative correlation was revealed for
      the motifs GGGG, ACTG, AAA and TAA. It was found that the likelihood of activity
      of an oligonucleotide against a desired mRNA target is sequence motif content
      dependent.

PMID- 10908348
TI  - An elongation factor-associating domain is inserted into human cysteinyl-tRNA
      synthetase by alternative splicing.
AB  - The amino acid sequence of human cytoplasmic cysteinyl-tRNA synthetase (CRS) was
      examined by analyzing sequences of genomic and expressed sequence tag fragments.
      From theses analyses, a few interesting possibilities were suggested for the
      structure of human CRS. First, different isoforms of CRS may result from
      alternative splicing. Second, the largest one would comprise 831 amino acids.
      Third, a new exon was identified encoding an 83 amino acid domain that is
      homologous to parts of elongation factor-1 subunits as well as other proteins
      involved in protein synthesis. Northern blot analysis showed three different
      mRNAs for CRS (of approximately 3.0, 2.7 and 2.0 kb) from human testis while only
      the 2.7 kb mRNA was commonly detected in other tissues. Expression of the exon 2
      containing transcript in testis was confirmed by RT-PCR and northern blotting.
      CRS containing the exon 2-encoded peptide retained catalytic activity comparable
      to that lacking this peptide. This peptide was responsible for the specific
      interaction of CRS with elongation factor-1gamma.

PMID- 10908349
TI  - The endonuclease activity of the yeast Dna2 enzyme is essential in vivo.
AB  - Dna2 is a multifunctional enzyme in yeast that possesses endonuclease activity
      well suited to remove RNA-DNA primers of Okazaki fragments, raising the question
      of whether endonuclease activity is essential for in vivo Dna2 function.
      Systematic site-directed mutations of amino acid residues in Saccharomyces
      cerevisiae DNA2 conserved in the central region of many eukaryotic DNA2 homologs
      allowed us to identify mutant dna2 alleles that were divided into three groups
      based on the viability of the mutant cells: (i) viable; (ii) inviable only when
      expression was repressed; (iii) inviable. Biochemical analyses of recombinant
      mutant Dna2 proteins isolated from the latter two groups revealed that they
      possessed normal ATPase/helicase activity, but were impaired in their
      endonuclease activity. Cells expressing mutant Dna2 enzymes partially impaired in
      endonuclease activity were viable, but were unable to grow when expression of
      their mutant Dna2 enzymes was further reduced. Their growth was restored when the
      mutant Dna2 proteins decreased in nuclease activity were induced to overexpress.
      In contrast, mutant Dna2 proteins lacking endonuclease activity did not allow
      cells to grow under any conditions tested. These in vivo and in vitro results
      demonstrate that the endonuclease activity of Dna2 is essential for Okazaki
      fragment processing.

PMID- 10908350
TI  - The MRE11-NBS1-RAD50 pathway is perturbed in SV40 large T antigen-immortalized AT
      1, AT-2 and HL-1 cardiomyocytes.
AB  - To investigate molecular controls of cardiomyocyte proliferation, we utilized
      cardiomyocytes induced to proliferate indefinitely by SV40 large T antigen (T
      ag). In the T-ag-immortalized AT-1, AT-2 and HL-1 cardiomyocytes, normal cellular
      proteins associating with T-ag and p53 were identified, isolated and micro
      sequenced. Peptide sequencing revealed that proteins of 90, 100 and 160 kDa were
      homologs of MRE11, NBS1 and RAD50, respectively. These three proteins play
      critical roles in the detection and repair of DNA double-strand breaks,
      activation of cell cycle checkpoints and telomere maintenance. In this report, we
      describe the cDNA cloning and double-strand sequencing of the rat homologs of
      MRE11, NBS1 and RAD50. We also determined the mRNA and protein levels of MRE11,
      NBS1 and RAD50 at different stages of heart development and in different tissues.
      MRE11 mRNA was only detected in the immortalized cardiomyocytes and in the
      testes. Although the 90 kDa MRE11 protein was seen in most samples examined, it
      was only detected at extremely low levels in proliferating cardiomyocytes (normal
      and immortalized). The 6.0 kb MRE11-related mRNA transcript (MRT) was seen in all
      samples examined. Levels of both NBS1 and RAD50 mRNA transcripts peaked in the
      heart at postnatal day 10. NBS1 mRNA levels were at very low levels in the T-ag
      immortalized AT-1, AT-2 and HL-1 cells but NBS1 protein was observed at extremely
      high levels. We propose that SV40 large T antigen's interaction with the MRE11
      NBS1-RAD50 pathway and with p53 ablates critical cell cycle checkpoints and that
      this is one of the major factors involved in the ability of this oncoprotein to
      immortalize cardiomyocytes.

PMID- 10908351
TI  - The nature of the 5'-terminus is a major determinant for DNA processing by
      Schizosaccharomyces pombe Rad2p, a FEN-1 family nuclease.
AB  - The nuclease activity of FEN-1 is essential for both DNA replication and repair.
      Intermediate DNA products formed during these processes possess a variety of
      structures and termini. We have previously demonstrated that the 5'-->3'
      exonuclease activity of the Schizosaccharomyces pombe FEN-1 protein Rad2p
      requires a 5'-phosphoryl moiety to efficiently degrade a nick-containing
      substrate in a reconstituted alternative excision repair system. Here we report
      the effect of different 5'-terminal moieties of a variety of DNA substrates on
      Rad2p activity. We also show that Rad2p possesses a 5'-->3' single-stranded
      exonuclease activity, similar to Saccharomyces cerevisiae Rad27p and phage T5 5'-
      >3' exonuclease (also a FEN-1 homolog). FEN-1 nucleases have been associated with
      the base excision repair pathway, specifically processing cleaved abasic sites.
      Because several enzymes cleave abasic sites through different mechanisms
      resulting in different 5'-termini, we investigated the ability of Rad2p to
      process several different types of cleaved abasic sites. With varying efficiency,
      Rad2p degrades the products of an abasic site cleaved by Escherichia coli
      endonuclease III and endonuclease IV (prototype AP endonucleases) and S.POMBE:
      Uve1p. These results provide important insights into the roles of Rad2p in DNA
      repair processes in S.POMBE:

PMID- 10908352
TI  - RNA aptamers that specifically bind to a 16S ribosomal RNA decoding region
      construct.
AB  - RNA-RNA recognition is a critical process in controlling many key biological
      events, such as translation and ribozyme functions. The recognition process
      governing RNA-RNA interactions can involve complementary Watson-Crick (WC) base
      pair binding, or can involve binding through tertiary structural interaction.
      Hence, it is of interest to determine which of the RNA-RNA binding events might
      emerge through an in vitro selection process. The A-site of the 16S rRNA decoding
      region was chosen as the target, both because it possesses several different RNA
      structural motifs, and because it is the rRNA site where codon/anticodon
      recognition occurs requiring recognition of both mRNA and tRNA. It is shown here
      that a single family of RNA molecules can be readily selected from two different
      sizes of RNA library. The tightest binding aptamer to the A-site 16S rRNA
      construct, 109.2-3, has its consensus sequences confined to a stem-loop region,
      which contains three nucleotides complementary to three of the four nucleotides
      in the stem-loop region of the A-site 16S rRNA. Point mutations on each of the
      three nucleotides on the stem-loop of the aptamer abolish its binding capacity.
      These studies suggest that the RNA aptamer 109.2-3 interacts with the simple 27
      nt A-site decoding region of 16S rRNA through their respective stem-loops. The
      most probable mode of interaction is through complementary WC base pairing,
      commonly referred to as a loop-loop 'kissing' motif. High affinity binding to the
      other structural motifs in the decoding region were not observed.

PMID- 10908353
TI  - Universal bases for hybridization, replication and chain termination.
AB  - Several unnatural, predominantly hydrophobic nucleobases that pack efficiently in
      duplex DNA without hydrogen bonding functionalities are reported to circumvent
      the hydrogen bonding-based specificity, both during oligonucleotide hybridization
      and enzymatic DNA synthesis. The reported nucleoside analogs are efficient
      'universal bases' for hybridization, template directed DNA synthesis and chain
      termination. Moreover, several of the universal bases function in their
      biological role, hybridization or replication, with an efficiency not
      significantly reduced relative to their natural counterparts.

PMID- 10908354
TI  - Homogeneous assays based on deoxyribozyme catalysis.
AB  - We report herein the first homogeneous assays based on the ribonuclease activity
      of a deoxyribozyme. The previously reported deoxyribozyme was covalently modified
      with biotin and used to assay biotin-binding interactions through changes in
      fluorescence upon substrate turnover. Deoxyribozymes with fluorescence-based
      reporting have the potential to serve as general analytical tools.

PMID- 10908355
TI  - DbClustal: rapid and reliable global multiple alignments of protein sequences
      detected by database searches.
AB  - DbClustal addresses the important problem of the automatic multiple alignment of
      the top scoring full-length sequences detected by a database homology search. By
      combining the advantages of both local and global alignment algorithms into a
      single system, DbClustal is able to provide accurate global alignments of highly
      divergent, complex sequence sets. Local alignment information is incorporated
      into a ClustalW global alignment in the form of a list of anchor points between
      pairs of sequences. The method is demonstrated using anchors supplied by the
      Blast post-processing program, Ballast. The rapidity and reliability of DbClustal
      have been demonstrated using the recently annotated Pyrococcus abyssi proteome
      where the number of alignments with totally misaligned sequences was reduced from
      20% to <2%. A web site has been implemented proposing BlastP database searches
      with automatic alignment of the top hits by DbClustal.

PMID- 10908357
TI  - Recognition of a cognate RNA aptamer by neomycin B: quantitative evaluation of
      hydrogen bonding and electrostatic interactions.
AB  - Aminoglycosides are an important class of antibiotic that selectively target RNA
      structural motifs. Recently we have demonstrated copper derivatives of amino
      glycosides to be efficient cleavage agents for cognate RNA motifs. To fully
      develop their potential as pharmaceutical agents it is necessary to understand
      both the structural mechanisms used by aminoglycosides to target RNA, and the
      relative contributions of hydrogen bonding and electrostatic interactions to
      recognition selectivity. Herein we report results from a calorimetric analysis of
      a stem-loop 23mer RNA aptamer complexed to the aminoglycoside neomycin B. Key
      thermodynamic parameters for complex formation have been determined by isothermal
      titration calorimetry, and from the metal-ion dependence of these binding
      parameters the relative contributions of electrostatics and hydrogen bonding
      toward binding affinity have been assessed. The principal mechanism for
      recognition and binding of neomycin B to the RNA major groove is mediated by
      hydrogen bonding.

PMID- 10908356
TI  - La protein has a positive effect on the translation of TOP mRNAs in vivo.
AB  - In vertebrates, the mRNAs encoding ribosomal proteins, as well as other proteins
      implicated in translation, are characterized by a 5'-untranslated region (5'
      UTR), including a stretch of pyrimidines at the 5'-end. The 5'-terminal
      oligopyrimidine (5'-TOP) sequence, which is involved in the growth-dependent
      translational regulation characteristic of this class of genes (so-called TOP
      genes), has been shown to specifically bind the La protein in vitro, suggesting
      that La might be implicated in translational regulation in vivo. In order to
      substantiate this hypothesis, we have examined the effect of La on TOP mRNA
      translational control in both stable and transient transfection experiments. In
      particular we have constructed and analyzed three stably transfected Xenopus cell
      lines inducible for overexpression of wild-type La or of putative dominant
      negative mutated forms. Moreover, La-expressing plasmids have been transiently co
      transfected together with a plasmid expressing a reporter TOP mRNA in a human
      cell line. Our results suggest that in vivo La protein plays a positive role in
      the translation of TOP mRNA. They also suggest that the function of La is to
      counteract translational repression exerted by a negative factor, possibly
      cellular nucleic acid binding protein (CNBP), which has been previously shown to
      bind the 5'-UTR downstream from the 5'-TOP sequence.

PMID- 10908359
TI  - The effect of chromatin structure on cisplatin damage in intact human cells.
AB  - The influence of chromatin structure on cisplatin DNA damage was investigated in
      intact human cells. The epsilon-globin gene promoter was utilised as the target
      DNA sequence and the terminal transferase-dependent PCR technique was employed to
      examine adduct formation at base pair resolution. It was found that cisplatin
      preferentially damaged at runs of consecutive guanine bases in intact cells. By
      comparing the relative intensity of adduct formation in intact cells and in
      purified genomic DNA, it was possible to assess the influence of chromatin
      proteins on the extent of cisplatin DNA damage. Enhanced damage in intact cells
      was found at the CACC site where a member of the Sp1 family of proteins is
      thought to bind. It is postulated that protein binding at this site bends the DNA
      double-helix so that enhanced cisplatin binding occurs. The altered DNA binding
      of cisplatin in the presence of chromatin proteins could be important in the
      properties of cisplatin as an anti-tumour drug.

PMID- 10908358
TI  - The role of 5'-leader length, secondary structure and PABP concentration on cap
      and poly(A) tail function during translation in Xenopus oocytes.
AB  - The 5'-cap structure and poly(A) tail of eukaryotic mRNAs function
      synergistically to promote translation initiation through a physical interaction
      between the proteins that bind to these regulatory elements. In this study, we
      have examined the effect of leader length and the presence of secondary structure
      on the translational competence and the function of the cap and poly(A) tail for
      mRNAs microinjected into Xenopus oocytes. Increasing the length of the 5'-leader
      from 17 to 144 nt resulted in a 2- to 4-fold increase in expression from an mRNA
      containing an unstructured leader but increased expression up to 20-fold for an
      mRNA containing 5'-proximal structure. Consequently, the presence of secondary
      structure was less inhibitory for those mRNAs with a longer 5'-leader. Co
      injection of poly(A)-binding protein (PABP) mRNA increased the function of the
      cap and poly(A) tail in promoting translation from poly(A)(+) but not poly(A)(-)
      mRNAs, particularly for mRNAs containing secondary structure. In the absence of
      an internal ribosome entry site, expression from the distal cistron of a
      dicistronic mRNA increased as a function of the length of the intercistronic
      region and the concentration of PABP. The inhibitory effect of intercistronic
      located secondary structure on translation was position-dependent. Indeed, the
      effect of secondary structure was abolished if positioned 134 nt upstream of the
      distal cistron. These data suggest that the length of a leader, the presence of
      secondary structure and the concentration of PABP determine the extent to which
      the cap and poly(A) tail regulate translation.

PMID- 10908360
TI  - Molecular characterization at the RNA and gene levels of U3 snoRNA from a
      unicellular green alga, Chlamydomonas reinhardtii.
AB  - A U3 snoRNA gene isolated from a Chlamydomonas reinhardtii (CRE:) genomic library
      contains putative pol III-specific transcription signals similar to those of RNA
      polymerase III-specific small nuclear (sn)RNA genes of higher plants. The 222 nt
      long CRE: U3 snoRNA was immunoprecipitated by anti-gamma-mpppN antisera, but not
      by anti-m(2,2,7)G antibodies, supporting the notion that it is a RNA polymerase
      III transcript. Tagged CRE: U3 snoRNA gene constructs were expressed in CRE:
      cells. Results of chemical and enzymatic structure probing of CRE: U3 snoRNA in
      solution and of DMS modification of CRE: U3 snoRNA under in vivo conditions
      revealed that the two-hairpin structure of the 5'-domain that is found in
      solution is no longer detected under in vivo conditions. The observed differences
      can be explained by the formation of several base pair interactions with the 18S
      and 5'-ETS parts of the pre-rRNA. A model that involves five intermolecular
      helices is proposed.

PMID- 10908361
TI  - Gut-enriched Kruppel-like factor represses cyclin D1 promoter activity through
      Sp1 motif.
AB  - Cancer cells differ from normal cells in many characteristics including loss of
      differentiation and uninhibited cell proliferation. Recent studies have focused
      on the identification of factors contributing to cell growth and differentiation.
      Gut-enriched Kruppel-like factor (GKLF or KLF4) is a newly identified eukaryotic
      transcription factor and has been shown to play a role in regulating growth
      arrest. We have previously shown that GKLF mRNA levels were significantly
      decreased in colon cancer tissues, and that over-expression of GKLF in colonic
      adenocarcinoma cells (HT-29) resulted in reduction of cyclin D1 (CD1) mRNA and
      protein levels. The current study was undertaken to determine the mechanisms by
      which GKLF inhibited CD1 expression. In a transient transfection system, GKLF
      suppressed CD1 promoter activity by 55%. Sequential deletion and site-directed
      mutation analysis of the CD1 promoter have identified the sequence between -141
      and -66, a region containing an Sp1 response element, to be essential for GKLF
      function. By electrophoretic mobility gel shift assay, recombinant GKLF and
      nuclear extracts from HT-29 cells were found to bind to the Sp1 motif on the CD1
      promoter. The inhibitory effect of GKLF on the CD1 promoter activity was
      completely abolished by excessive amount of Sp1 DNA and GKLF significantly
      reduced the stimulatory function of Sp1 suggesting that GKLF and Sp1 may compete
      for the same binding site on the CD1 promoter. These results indicate that GKLF
      is a transcriptional repressor of the CD1 gene and that the inhibitory effect of
      GKLF is, in part, mediated by interaction with the Sp1 binding domain on its
      promoter.

PMID- 10908362
TI  - 4-amino-1H-benzo[g]quinazoline-2-one: a fluorescent analog of cytosine to probe
      protonation sites in triplex forming oligonucleotides.
AB  - We developed a new fluorescent analog of cytosine, the 4-amino-1H
      benzo[g]quinazoline-2-one, which constitute a probe sensitive to pH. The 2'-O-Me
      ribonucleoside derivative of this heterocycle was synthesized and exhibited a
      fluorescence emission centered at 456 nm, characterized by four major excitation
      maxima (250, 300, 320 and 370 nm) and a fluorescence quantum yield of Phi = 0.62
      at pH 7.1. The fluorescence emission maximum shifted from 456 to 492 nm when pH
      was decreased from 7.1 to 2.1. The pK(a) (4) was close to that of cytosine
      (4.17). When introduced in triplex forming oligonucleotides this new nucleoside
      can be used to reveal the protonation state of triplets in triple-stranded
      structures. Complex formation was detected by a significant quenching of
      fluorescence emission (approximately 88%) and the N-3 protonation of the
      quinazoline ring by a shift of the emission maximum from 485 to 465 nm. Using
      this probe we unambiguously showed that triplex formation of the pyrimidine motif
      does not require the protonation of all 4-amino-2-one pyrimidine rings.

PMID- 10908363
TI  - Compaction of DNA in an anionic micelle environment followed by assembly into
      phosphatidylcholine liposomes.
AB  - A difficult problem concerning the interaction of DNA with amphiphiles of
      opposite charge above their critical micelle concentration is the propensity for
      aggregation of the condensed DNA complexes. In this study, this problem was
      addressed by attenuating amphiphile charge density within a cholate micelle
      environment. The amphiphile consisted of a cationic peptide, acetyl-CWKKKPKK
      amide, conjugated to dilaurylphos-phatidylethanolamine. In the presence of
      cholate, multiple equivalents of cationic charge were required to bring about the
      completion of DNA condensation. At the end point of condensation, stable, soluble
      DNA-micelle complexes were formed, which by dynamic light scattering exhibited
      apparent hydro-dynamic diameters between 30 and 60 nm. Aggregation, as measured
      by static light scattering at 90 degrees and by turbidity, was not observed until
      further additions of peptide-lipid conjugate were made beyond the end point of
      DNA condensation. Liposome complexes containing the non-aggregated, compacted DNA
      were formed by adding dioleoylphosphatidylcholine followed by removing the
      cholate by dialysis. The resulting complexes were distributed within a narrow
      density range, the DNA was quantitatively assembled into the liposomes, and
      liposomes without DNA were not detected. Small particles were formed with a mean
      hydrodynamic diameter of 77 nm. The liposomal DNA showed complete retention of
      its supercoiled form and no detectable sensitivity to DNase (25 U/10 microg DNA,
      1.5 h, 37 degrees C). The use of an anionic, dialyzable amphiphile to attenuate
      charge inter-actions between DNA and cationic amphiphiles is a useful technology
      for the quantitative assembly of compacted DNA into conventional liposomes, with
      complete protection against nuclease activity.

PMID- 10908364
TI  - Two Tetrahymena G-DNA-binding proteins, TGP1 and TGP3, share novel motifs and may
      play a role in micronuclear division.
AB  - G-DNA is a four-stranded DNA structure with diverse putative biological roles. We
      have previously purified and cloned a novel G-DNA-binding protein TGP1 from the
      ciliate Tetrahymena thermophila. Here we report the molecular cloning of TGP3, an
      additional G-DNA-binding protein from the same organism. The TGP3 cDNA encodes a
      365 amino acid protein that is homologous to TGP1 (34% identity and 44%
      similarity). The proteins share a sequence pattern that contains two novel
      repetitive and homologous motifs flanking an extensively hydrophilic and basic
      region. A nuclear fractionation experiment showed that TGP1 and TGP3 activities
      are localized predominantly in the nuclear fraction. To further investigate the
      biological roles of the proteins in vivo, we have generated separate macronuclear
      gene knockout (KO) strains (TGP1KO and TGP3KO) for each of the two genes.
      Southern blot analysis demonstrated that the macronuclear copies of each gene
      were completely disrupted. Mobility shift assays showed that the corresponding G
      DNA-binding activity for each protein was abolished in the KO strains. Growth
      analysis showed that both KO strains grew at near wild-type rates, indicating
      that neither of the genes is essential for cell growth. Nevertheless, nuclear
      staining analysis revealed that both TGP1KO and TGP3KO cells have an increased
      occurrence (more than 2-fold) of extra micronuclei, implying faulty control of
      micronuclear division in the KO cells.

PMID- 10908366
TI  - Automated one-step DNA sequencing based on nanoliter reaction volumes and
      capillary electrophoresis.
AB  - An integrated system with a nano-reactor for cycle-sequencing reaction coupled to
      on-line purification and capillary gel electrophoresis has been demonstrated.
      Fifty nanoliters of reagent solution, which includes dye-labeled terminators,
      polymerase, BSA and template, was aspirated and mixed with the template inside
      the nano-reactor followed by cycle-sequencing reaction. The reaction products
      were then purified by a size-exclusion chromatographic column operated at 50
      degrees C followed by room temperature on-line injection of the DNA fragments
      into a capillary for gel electrophoresis. Over 450 bases of DNA can be separated
      and identified. As little as 25 nl reagent solution can be used for the cycle
      sequencing reaction with a slightly shorter read length. Significant savings on
      reagent cost is achieved because the remaining stock solution can be reused
      without contamination. The steps of cycle sequencing, on-line purification,
      injection, DNA separation, capillary regeneration, gel-filling and fluidic
      manipulation were performed with complete automation. This system can be readily
      multiplexed for high-throughput DNA sequencing or PCR analysis directly from
      templates or even biological materials.

PMID- 10908365
TI  - By-passing selection: direct screening for antibody-antigen interactions using
      protein arrays.
AB  - We have developed a system to identify highly specific antibody-antigen
      interactions by protein array screening. This removes the need for selection
      using animal immunisation or in vitro techniques such as phage or ribosome
      display. We screened an array of 27 648 human foetal brain proteins with 12 well
      expressed antibody fragments that had not previously been exposed to any antigen.
      Four highly specific antibody-antigen pairs were identified, including three
      antibodies that bind proteins of unknown function. The target proteins were
      expressed at a very low copy number on the array, emphasising the unbiased nature
      of the screen. The specificity and sensitivity of binding demonstrates that this
      'naive' screening approach could be applied to the high throughput isolation of
      specific antibodies against many different targets in the human proteome.

PMID- 10908367
TI  - Discriminating duplex and hairpin oligonucleotides using chemical shifts:
      application to the anticodon stem-loop of Escherichia coli tRNA(Phe).
AB  - A sensitive NMR spectroscopic method for detection of duplex forms of self
      complementary nucleic acid sequences has been implemented. The G.U wobble base
      pair formed between a (15)N-labeled strand and an unlabeled probe strand is used
      to identify the duplex. The guanine imino resonance, with its characteristic
      chemical shift, is detected using a 2D (15)N-(1)H heteronuclear multiple quantum
      coherence (HMQC) spectrum and provides a sensitive and unambiguous route to
      hairpin-duplex discrimination. The method has been used to identify the duplex
      and hairpin forms of an RNA oligonucleotide at concentrations of approximately 20
      microM. This method has also been used to rule out possible duplex formation of
      an RNA oligonucleotide corresponding to the unmodified anticodon stem-loop of
      Escherichia coli tRNA(Phe) and suggests that this hairpin has a 3 nt loop.

PMID- 10908369
TI  - Safe practice of endoscopy.

PMID- 10908368
TI  - Comparison of the levels of 8-hydroxyguanine in DNA as measured by gas
      chromatography mass spectrometry following hydrolysis of DNA by Escherichia coli
      Fpg protein or formic acid.
AB  - 8-hydroxyguanine (8-OH-Gua) is one of many lesions generated in DNA by oxidative
      processes including free radicals. It is the most extensively investigated
      lesion, due to its miscoding properties and its potential role in mutagenesis,
      carcinogenesis and aging, and also to the existence of analytical methods using
      HPLC and gas chromatography mass spectrometry (GC/MS). Some studies raised the
      possibility of artifacts generated during sample preparation. We investigated
      several experimental conditions in order to eliminate possible artifacts during
      the measurement of 8-OH-Gua by GC/MS. Derivatization has been reported to produce
      artifacts by oxidation of guanine to 8-OH-Gua in acid-hydrolysates of DNA,
      although the extent of artifacts seems to depend on experimental conditions. For
      removal of 8-OH-Gua from DNA, we used either formic acid hydrolysis or specific
      enzymatic hydrolysis with Escherichia coli Fpg protein. Derivatization of enzyme
      hydrolysates should not generate additional 8-OH-Gua because of the absence of
      guanine, which is not released by the enzyme, whereas guanine released by acid
      may be oxidized to yield 8-OH-Gua. The measurement of 8-OH-Gua in calf thymus DNA
      by GC/isotope-dilution MS (GC/IDMS) using these two different hydrolyses yielded
      similar levels of 8-OH-Gua. This indicated that no artifacts occurred during
      derivatization of acid-hydrolysates of DNA. Pyridine instead of acetonitrile and
      room temperature were used during derivatization. Pyridine reduced the level of 8
      OH-Gua, when compared with acetonitrile, indicating its potential to prevent
      oxidation. Two different stable-isotope labeled analogs of 8-OH-Gua used as
      internal standards for GC/IDMS analysis yielded similar results. A comparison of
      the present results with the results of recent trials by the European Standards
      Committee for Oxidative DNA Damage (ESCODD) is also presented.

PMID- 10908370
TI  - A clinicopathological classification of granulomatous disorders.
AB  - Granulomatous disorders comprise a large family sharing the histological
      denominator of granuloma formation. A granuloma is a focal compact collection of
      inflammatory cells, mononuclear cells predominating, usually as a result of the
      persistence of a non-degradable product and of active cell mediated
      hypersensitivity. There is a complex interplay between invading organism or
      prolonged antigenaemia, macrophage activity, a Th1 cell response, B cell
      overactivity and a vast array of biological mediators. Differential diagnosis and
      management demand a skilful interpretation of clinical findings and pathological
      evidence. They are classified into infections, vasculitis, immunological
      aberration, leucocyte oxidase deficiency, hypersensitivity, chemicals, and
      neoplasia.

PMID- 10908371
TI  - Endomysial antibody in the diagnosis and management of coeliac disease.
AB  - This review determines the significance, usefulness, and application of the
      endomysial antibody test for coeliac disease in clinical practice.

PMID- 10908372
TI  - Chronic inflammatory bowel disease in children: a complex problem in management.

PMID- 10908373
TI  - Images in Medicine. Cutaneous anthrax.

PMID- 10908374
TI  - Mucins and inflammatory bowel disease.
AB  - There is a layer of mucus lining the gastrointestinal tract, which acts as both a
      lubricant and as a physical barrier between luminal contents and the mucosal
      surface. The mucins that make up this layer consist of a protein backbone with
      oligosaccharides attached to specific areas of the protein core. These areas are
      called the variable number tandem repeat regions. The degree of glycosylation of
      the mucins is central to their role in the mucus barrier. The oligosaccharides
      are variable and complex. It has been demonstrated that the degree of sulphation
      and sialylation and the length of the oligosaccharide chains all vary in
      inflammatory bowel disease. These changes can alter the function of the mucins.
      Mucins are broadly divided into two groups, those that are secreted and those
      that are membrane bound. The major mucins present in the colorectum are MUC1,
      MUC2, MUC3, and MUC4. Trefoils are a group of small peptides that have an
      important role in the mucus layer. Three trefoils have been demonstrated so far.
      They seem to play a part in mucosal protection and in mucosal repair. They may
      help to stabilise the mucus layer by cross linking with mucins to aid formation
      of stable gels. Trefoils can be expressed in the ulcer associated cell lineage, a
      glandular structure that can occur in the inflamed mucosa. There seem to be
      differences in the expression of trefoils in the colon and the small bowel, which
      may imply different method of mucosal repair.

PMID- 10908375
TI  - Pathophysiology of chronic bacterial osteomyelitis. Why do antibiotics fail so
      often?
AB  - In this review the pathophysiology of chronic bacterial osteomyelitis is
      summarised, focusing on how bacteria succeed so often in overcoming both host
      defence mechanisms and antibiotic agents. Bacteria adhere to bone matrix and
      orthopaedic implants via receptors to fibronectin and to other structural
      proteins. They subsequently elude host defences and antibiotics by "hiding"
      intracellularly, by developing a slimy coat, or by acquiring a very slow
      metabolic rate. The presence of an orthopaedic implant also causes a local
      polymorphonuclear cell defect, with decreased ability to kill phagocytosed
      bacteria. Osteolysis is determined locally by the interaction of bacterial
      surface components with immune system cells and subsequent cytokine production.
      The increasing development of antibiotic resistance by Staphylococcus aureus and
      S epidermidis will probably make conservative treatment even less successful than
      it is now. A close interaction between orthopaedic surgeons and physicians, with
      combined medical and operative treatment, is to be commended.

PMID- 10908376
TI  - Foreign bodies in the nasal cavities: a comprehensive review of the aetiology,
      diagnostic pointers, and therapeutic measures.
AB  - Otolaryngologists frequently encounter nasal foreign bodies, particularly among
      children and mentally retarded patients. There are isolated reports describing
      the removal of unusual foreign bodies from the nose. But no comprehensive reviews
      of this important subject have been published for many years. This article
      includes a detailed discussion of the different types of nasal foreign bodies,
      the various clinical presentations, management options, and complications
      associated with nasal foreign bodies.

PMID- 10908377
TI  - Ultrasonographic findings and differentiation of benign and malignant focal
      splenic lesions.
AB  - The purpose of this study was to analyse the sonographic findings of focal
      splenic lesions with an attempt to differentiate benign lesions from
      malignancies. The sonographic findings of 53 cases of verified focal splenic
      lesions, excluding post-traumatic haematomas and phleboliths, were
      retrospectively analysed. Of the 53 cases, 30 cases (57%) were benign and 23
      cases (43%) were malignant. The malignancies included lymphoma (n=13), metastases
      (n=10); while the benign lesions included cysts (n=17), infarcts (n=3), and
      abscesses (n=5), and one case each of haemangioma, hamartoma, spontaneous
      rupture, tuberculosis, and lymphangioma. Significant differences were noted
      between the benign and malignant groups with respect to the presence of solitary
      lesions (p<0.0001), anechoic mass (p<0. 0001), lesions with highly echogenic foci
      due to gas or calcification (p = 0.0303), hyperechoic/mixed echoic lesions (p<0.
      0001), presence of extrasplenic abdominal masses (p<0.0001), and nodules with the
      target sign (p<0.0001). Solitary lesions, anechoic mass, and lesions with highly
      echogenic foci due to gas or calcification each had a positive predictive value
      of 85%, 100%, and 100%, respectively, for the lesions to be benign. The
      multifocal/diffuse lesions, presence of extrasplenic abdominal masses,
      hyperechoic/mixed echoic lesions, and nodules with the target sign each had a
      positive predictive value of 70%, 100%, 70%, and 100%, respectively, for the
      lesions to be malignant. In summary, focal lesions with anechoic pattern or
      echogenic foci due to gas or calcification are suggestive signs of benign
      process. The sonographic observations of multifocal or diffuse solid lesions,
      especially those associated with target sign or extrasplenic abdominal masses are
      suggestive of malignancy.

PMID- 10908378
TI  - General surgery in haemophiliac patients.
AB  - With improvements in medical technology, more and larger surgical procedures are
      performed in haemophiliac patients, but rarely reported in the surgical
      literature. A retrospective study from a 10 year period from one referral centre
      identified a total of 68 operations performed in haemophiliac patients. The
      levels of the defective factors were carefully monitored preoperatively and
      postoperatively, and replaced according to a standard formula. Special caution
      was taken to avoid any postoperative medication or procedures that could provoke
      haemorrhagic complications.Two patients suffered postoperative bleeding
      complications that were managed conservatively. Inhibitory factors were detected
      preoperatively in one case, and postoperatively in another, and were managed with
      aggressive replacement therapy. There was no mortality, and the overall morbidity
      rate was 6%. With adequate preoperative and postoperative monitoring of the
      clotting factors, meticulous haemostasis during surgery, careful postoperative
      nursing, and timely replacement therapy, haemophiliac patients can be operated
      with good results. Postoperative bleeding complications are rare, and usually
      amenable to conservative management.

PMID- 10908379
TI  - Management of spontaneous pneumothorax-a Welsh survey.
AB  - The authors sought to determine to what degree current practice by hospital
      physicians and accident and emergency (A&E) departments in Wales conformed to the
      British Thoracic Society's guidelines for the management of spontaneous
      pneumothorax. Questionnaires were posted to all consultants involved in emergency
      medical admissions in Wales (149 consultant physicians and 23 A&E consultants) of
      whom 101 (59%) replied. Only 45% used the classification, "small, moderate, or
      complete" to describe the size of pneumothorax. Just 44% would do as recommended
      by the British Thoracic Society and discharge an asymptomatic patient with a
      primary pneumothorax and 34% would discharge a patient with a primary
      pneumothorax after successful aspiration. Only 20% were prepared to try
      aspiration initially for a secondary pneumothorax with a complete lung collapse.
      Thirty four per cent would follow the recommendation to remove a chest drain
      without prior clamping of the tube 24 hours after bubbling had stopped. In the
      event of a persistent air leak 69% would refer patients or seek a specialist
      opinion. Physicians with an interest in respiratory medicine tolerated persistent
      air leaks for significantly longer than did non-respiratory physicians (median of
      7 v 5 days, p=0.001). The survey indicates that fewer than expected consultant
      physicians and A&E consultants in Wales manage spontaneous pneumothoraces in the
      way recommended by the guidelines. Physicians with an interest in respiratory
      medicine tended to comply with these guidelines more than general physicians with
      interests other than respiratory medicine or A&E consultants but the trend was
      not significant at the 5% level. It is felt that the guidelines should be
      disseminated more widely, ensuring that emergency admissions units and A&E
      departments have copies on display or easily accessible, and that they could be
      expanded to cover other aspects such as timing for surgery.

PMID- 10908380
TI  - Anaphylactoid reactions to paracetamol.
AB  - The toxic effects of paracetamol in overdose quantities are well recognised but
      the occurrence of anaphylactoid reactions to paracetamol is infrequently
      identified by consumers and health care professionals. Nevertheless adverse
      reactions to this drug, even in therapeutic doses, can have fatal or near fatal
      consequences. A case of an anaphylactoid reaction to paracetamol is described.

PMID- 10908381
TI  - Commentary-anaphylactic reactions to paracetamol.

PMID- 10908382
TI  - Alcoholic hepatitis-the case for intensive management.
AB  - Alcoholic hepatitis is a common condition with a high mortality. Although
      treatment options for established alcoholic hepatitis are limited, many of the
      complications of this condition are preventable. This case report and discussion
      illustrate the important role of early diagnosis and intervention in this patient
      group. Important management points are stressed to aid physicians who may
      encounter this condition rarely.

PMID- 10908383
TI  - Bilateral adrenal non-Hodgkin's lymphoma with adrenal insufficiency.
AB  - A 74 year old women presented with lethargy and weight loss and was found to have
      profound adrenal insufficiency and bilateral adrenal mass lesions. Histological
      examination revealed non-Hodgkin's lymphoma. There was no evidence of lymphoma
      outside the adrenal glands. Isolated bilateral adrenal masses may rarely be due
      to primary adrenal non-Hodgkin's lymphoma, which is often associated with adrenal
      insufficiency.

PMID- 10908385
TI  - Renal colic in a young woman. Diagnosis: intravesical stenotic ureterocele
      containing a calculus.

PMID- 10908384
TI  - A 60 year old woman with axillary mass. Diagnosis: axillary lymphadenitis:
      filarial.

PMID- 10908386
TI  - An unusual cause of watery diarrhoea. Diagnosis: metastatic Zollinger-Ellison
      syndrome.

PMID- 10908387
TI  - A patient presenting with hoarseness. Diagnosis: sarcoidosis.

PMID- 10908388
TI  - Young male with headache, blindness, and hypogonadism. Diagnosis:
      craniopharyngioma presenting with hypogonadotrophic hypogonadism.

PMID- 10908389
TI  - Right shoulder pain in a body builder. Diagnosis: stress induced osteolysis of
      the right distal clavicle.

PMID- 10908390
TI  - Unexpected elevation of parathyroid hormone in an asymptomatic patient with
      multiple endocrine neoplasia syndrome type 2A. Diagnosis: erroneous findings due
      to blood samples being taken from site of autotransplantation of parathyroid
      tissue.

PMID- 10908391
TI  - HIV infection and seizures.

PMID- 10908392
TI  - Medical restrictions to driving: awareness of patients and doctors.

PMID- 10908393
TI  - Addison's disease in type I diabetes, presenting with recurrent hypoglycaemia.

PMID- 10908394
TI  - A patient presenting with hoarseness

PMID- 10908395
TI  - Young male with headache, blindness, and hypogonadism

PMID- 10908397
TI  - Unexpected elevation of parathyroid hormone in an asymptomatic patient with
      multiple endocrine neoplasia syndrome type 2A

PMID- 10908396
TI  - Right shoulder pain in a body builder

PMID- 10908399
TI  - Instant notes in immunology

PMID- 10908398
TI  - Bedside cardiology

PMID- 10908400
TI  - Lee's synopsis of anaesthesia

PMID- 10908401
TI  - Benefits and hazards of exercise

PMID- 10908402
TI  - Guide to working in europe for doctors

PMID- 10908403
TI  - Blood pressure measurement

PMID- 10908405
TI  - Osteobiology, strain, and microgravity: part I. Studies at the cellular level.

PMID- 10908406
TI  - Systematic review of randomized trials of the effect of exercise on bone mass in
      pre- and postmenopausal women.
AB  - Studies of the effect of exercise programs on bone mass appear inconsistent. Our
      objective was to systematically review and meta-analyze randomized trials of the
      effect of exercise on bone mass in pre- and postmenopausal women. A computerized
      MEDLINE search was conducted for the years 1966-1997. Thirty-five randomized
      trials were identified. Meta-analytic methods were used to statistically pool
      results of studies of the effect of impact (e.g., aerobics) and non-impact (e.g.,
      weight training) exercise on the lumbar spine and femoral neck. The most studied
      bone site was the lumbar spine in postmenopausal women (15 studies), where both
      impact [1.6% bone loss prevented, 95% confidence intervals (CI): 1.0%-2.2%] and
      non-impact (1.0%, 95% CI: 0.4%-1.6%) exercise programs had a positive effect.
      Results for the lumbar spine in premenopausal women (eight studies) were similar:
      1.5% (95% CI: 0.6%-2.4%) less bone loss (or net gain) after impact exercise and
      1.2% (95% CI: 0.7%-1.7%) after non-impact exercise. Impact exercise programs
      appeared to have a positive effect at the femoral neck in postmenopausal women
      (five studies), 1.0% (95% CI: 0.4%-1.6%) bone loss prevented, and possibly in
      premenopausal women, 0.9% (95% CI: -0.2%-2.0%) bone loss prevented. There were
      too few trials to draw conclusions from meta-analyses of the effect of non-impact
      exercise on the neck of femur. This systematic review of randomized trials shows
      that both impact and non-impact exercise have a positive effect at the lumbar
      spine in pre- and postmenopausal women. Impact exercise probably has a positive
      effect at the femoral neck. More studies are required to determine the optimal
      intensity and type of exercise.

PMID- 10908407
TI  - Comparison of quantitative calcaneal ultrasound and dual energy X-ray
      absorptiometry in the evaluation of osteoporotic risk in children with chronic
      rheumatic diseases.
AB  - Osteoporosis is a common complication in children with chronic rheumatic diseases
      (CRD). Although dual energy X-ray absorptiometry (DXA) is increasingly being used
      to determine bone mineral density (BMD) in children, it exposes the subject to
      ionizing radiation and does not provide a measure of true bone density; in fact,
      in growing bones the increase in BMD is mainly caused by the increase in bone
      size. In recent years, quantitative ultrasound techniques (QUS) have been used in
      radiation-free assessment of bone density and "bone quality" by measurement of
      the ultrasound waves attenuation by bone (BUA). In the present study we made a
      direct comparison of BUA in the calcaneum, determined by the pediatric contact
      ultrasound bone analyzer (CUBA) with lumbar BMD measured by DXA, in a group of 6
      18-year-old patients with CRD. The study group consisted of 53 patients affected
      with juvenile rheumatoid arthritis (n = 29), systemic lupus erythematosus (n =
      13), and juvenile dermatomyositis (n = 11). Mean age was 13.02 +/- 2.69 years. In
      22 patients (19 girls, 3 boys) both DXA and CUBA were repeated after 1 year in
      order to assess the mean percentage rate of BMD and BUA change over this time.
      Both lumbar spine BMD and calcaneal BUA measurements were lower in the CRD
      patients compared with a control group (P < 0.001). Calcaneal BUA was
      significantly correlated (r = 0.83, P < 0.001) with lumbar spine BMD. Age and sex
      correction (Z-score) did not change the relationship between BUA and BMD (r =
      0.80, P < 0.001). A significant correlation between the mean percentage of
      variation (delta%) of BMD and BUA (r = 0.76, P < 0.001) was also demonstrated in
      the 22 patients who were evaluated prospectively. Portability, ease of use, lower
      cost, and absence of radiation make CUBA a promising means of evaluating BMD in
      children.

PMID- 10908408
TI  - Imaging ultrasonometry of the calcaneus: dependence on calcaneal area.
AB  - The purpose of this study was (1) to investigate the dependence of broadband
      ultrasound attenuation (BUA) and speed of sound (SOS) measured in a circular
      region of interest (ROI) having a fixed size on calcaneal area and (2) to examine
      whether the normalization of ultrasonic variables for the area of the calcaneus
      provides better differentiation of diseased subjects from healthy individuals.
      Ultrasound variables were estimated in 169 healthy postmenopausal women (mean age
      66.5 years, range 42-87 years) and 39 women with vertebral fractures (mean age
      72.9 years, range 51-86 years). A minimum attenuation ROI, 15 mm in diameter,
      with a commercial imaging ultrasonometer was used. Significant relationships were
      found between both ultrasonic variables and calcaneal area (r2 = 0.06, P < 0.001
      for BUA, r2 = 0.12, P < 0.0001 for SOS). Normalization of ultrasound variables
      (BUAn and SOSn) was based on the regression equations of the relationships among
      BUA, SOS, and calcaneal area. In a precision study, nine women were examined five
      times each to determine the errors arising from both the repositioning of the
      foot and selection of the calcaneal area. The reproducibility errors of BUA, SOS,
      BUAn, SOSn, and area were 0.87%, 0.20%, 1.07%, 0.27%, and 3.72%, respectively.
      Significant differences were found between the areas under the ROC curve for BUAn
      and BUA (area under the curve = 0.93 for BUAn versus 0.90 for BUA, P = 0.003) as
      well as for SOSn and SOS (area under the curve = 0.85 for SOSn versus 0.79 for
      SOS, P = 0.003). Normalization of ultrasound variables for calcaneal area
      improves the discrimination of clinical studies.

PMID- 10908409
TI  - Peripheral volumetric bone mineral density in pre- and postmenopausal Chinese
      women in Hong Kong.
AB  - The aim of this cross-sectional study was to use a newly available precise and
      multislice pQCT (Densiscan 2000) for establishing reference data of volumetric
      bone mineral density (vBMD) of the distal radius. vBMD of the nondominant wrist
      was measured in 118 healthy Hong Kong Chinese women aged 41-60. Anthropometric
      parameters, menstrual status, and handgrip strength were also measured. Results
      showed that there was a significant age-related decline in trabecular BMD (tBMD),
      integral BMD (iBMD), and cortical BMD (cBMD), with correlation coefficients
      ranging from -0.401 to -0.547 (P < 0.001). The annual decline of vBMD was 2.22%,
      1.79%, and 0.88% in tBMD, iBMD, and cBMD, respectively. When subjects were
      divided into premenopausal and postmenopausal groups, we found an age-related
      decline in tBMD and iBMD, but not in cBMD in both groups. The vBMD values
      interpreted in mg/cm3 in premenopausal women were 238.4 +/- 57.2 in tBMD, 604.6
      +/- 82.9 in iBMD, 1415.5 +/- 129.9 in cBMD, and declined significantly (all P <
      0.001) to 193.7 +/-54.7 in tBMD, 500.0 +/- 90.3 in iBMD, and 1306.7 +/- 153.5 in
      cBMD in the postmenopausal women. On average, 16.7% of the subjects showed their
      vBMDs to be below-1 SD and only 1.7% of them lower than -2 SD. Linear regression
      showed that the annual decline of vBMD was faster in postmenopausal women with
      2.42% in tBMD, 1.90% in iBMD, and 0.88% in cBMD compared with 1.91% in tBMD,
      0.98% in iBMD, and 0.55% in cBMD in the premenopausal women. After adjustment for
      age, only the iBMD with dominant trabecular elements showed a significantly
      accelerated decrease after the onset of menopause (P = 0.008). Weak or no
      association was found among vBMDs with anthropometric parameters, years since
      menopause, or handgrip strength. In conclusion, we found a significant age
      related decline of vBMDs in Hong Kong Chinese women aged 41-60 years,
      characterized by the early reduction of metabolically active trabecular bone
      after entering the fourth decade of life, with an accelerated decline after the
      onset of menopause.

PMID- 10908410
TI  - Ultrasonographic, axial, and peripheral measurements in female patients with
      benign hypermobility syndrome.
AB  - Twenty-five female Caucasians, aged 19-57 years, with the hypermobility syndrome
      had bone density measurements using established noninvasive techniques such as
      dual X-ray absorptiometry (DXA), single photon absorptiometry (SPA), heel
      ultrasound (US), and peripheral computed tomography (pQCT) acquisitions of the
      radius. As a group, comparisons of the different bone indices with the
      corresponding age-matched reference population resulted in normal z-scores for
      the arial densities, however, values for the volumetric total and cortical bone
      at the radius measured by pQCT were significantly lower than expected (P <
      0.0001). Spinal and femoral bone density results were significant after
      correction for body mass index (BMI). This cross-sectional study shows that the
      benign hypermobility syndrome patients have lowered t-scores for data reflecting
      bone structure and bone strength as measured with US and the tomographic
      technique.

PMID- 10908411
TI  - Time pattern of exercise-induced changes in type I collagen turnover after
      prolonged endurance exercise in humans.
AB  - Type I collagen is known to adapt to physical activity, and biomarkers of
      collagen turnover indicate that synthesis can be influenced by a single intense
      exercise bout, but the exact time pattern of these latter changes are largely
      undescribed. In the present study, 17 healthy young males had their plasma
      concentrations of the carboxyterminal propeptide of type I procollagen (PICP), a
      marker of collagen formation, and the immunoactive carboxyterminal cross-linked
      telopeptide (ICTP), a marker of collagen resorption, measured before and
      immediately postexercise, as well as 1, 2, 3, 4, 5, and 6 days after completion
      of a marathon run (42 km). Serum concentrations of creatine kinase (S-CK) were
      measured as an indicator of muscular breakdown in response to the exercise bout.
      After a transient decrease in collagen formation immediately after exercise
      (plasma PICP concentration: 176 +/- 17 microg/liter to 156 +/- 9 microg/liter)(P
      < 0.05), concentrations rose in the days following the marathon, peaked 72 hours
      after exercise (197 +/- 8 microg/liter)(P < 0.05 versus basal), and returned to
      basal values similar to those 5 days postexercise (170 +/- 10 microg/liter).
      Apart from a short increase immediately after exercise, collagen resorption did
      not change from basal levels throughout the remaining period (P > 0.05). Muscle
      breakdown was elevated during the days following the exercise and peaked 24 hours
      after the exercise (S-CK concentration: 3,133 +/- 579 U/liter). The findings in
      the present study indicate that type I collagen synthesis is accelerated in
      response to prolonged strenuous exercise, reaching a peak after 3 days and
      returning to preexercising levels 5 days after the completion of a marathon run.

PMID- 10908412
TI  - Influence of growth hormone on a new marker of cartilage metabolism (chondrex).
AB  - The aim of this study was to evaluate the usefulness of a major secretory protein
      of human chondrocytes (chondrex) as a potential serum marker of bone
      responsiveness to growth hormone (GH). The study included 18 children (10 F, 8
      M), aged 10.9 +/- 2.3 years, bone age 8.8 +/- 2.7 years, height -2.3 +/- 0.22
      SDS, affected by isolated idiopathic GH deficiency (GHD). Serum samples for
      evaluation of chondrex, total, and bone alkaline phosphatase were taken before
      and 3 and 6 months following treatment with rhGH. The basal serum level of
      chondrex did not differ between patients (37 +/- 22 ng/ml) and controls (33 +/-
      9.8 ng/ml). Following 6 months of treatment with rhGH, a significant increase of
      height velocity SDS (from -2.8 +/- 0.5 to 1.3 +/- 0.7), total (from 195 +/- 47 to
      264 +/- 79 U/liter) and bone alkaline phosphatase (from 81 +/- 21 to 108 +/- 30
      U/liter) was observed, while chondrex serum level remained unchanged (from 37 +/-
      22 to 36 +/- 29 ng/ml). It was concluded that chondrex cannot be considered a
      reliable marker of bone responsiveness to GH in the growing child.

PMID- 10908413
TI  - Effects of estrogen and progesterone on tibia histomorphometry in growing rats.
AB  - The present study was performed to evaluate possible interactions between
      estrogen and progesterone on peak cancellous bone mass. Ovariectomized (OVX)
      growing rats were treated with 17beta-estradiol (4.8 microg/day), progesterone
      (4.8 mg/day), a combination of the two sex steroids, or with vehicle for 14 days
      beginning 7 days after OVX. The tibiae were removed for histomorphometric
      analysis of the proximal metaphysis. OVX and growth each resulted in net
      resorption of cancellous bone at a sampling site adjusted for longitudinal bone
      growth. Estradiol and progesterone treatment each antagonized bone loss by
      inhibiting the decrease in trabecular number. Estradiol increased but
      progesterone had no effect on trabecular thickness. Progesterone did not
      influence either osteoclast number or the resorption of the pretreatment
      fluorochrome label. Estradiol reduced osteoclast number and inhibited label
      resorption, the latter change being accentuated by combination treatment.
      Estradiol reduced and progesterone enhanced the mineral apposition and bone
      formation rates. The results indicate that estradiol and progesterone have
      independent activities on cancellous bone turnover during growth. Whereas
      estradiol reduced bone turnover, progesterone had a stimulatory effect on bone
      formation. These findings suggest that progesterone has a role in establishing
      and maintaining peak cancellous bone volume during growth.

PMID- 10908414
TI  - Calcium mobilization is required for spreading in human osteoblasts.
AB  - Adhesion-induced changes in intracellular calcium concentration ([Ca2+]i) were
      measured in populations of human osteoblasts spreading on bone matrix proteins.
      In cells spreading on collagen type I, fibronectin, or laminin, average values
      for [Ca2+]i were found to increase approximately 2x over baseline and then
      decline. The speed with which [Ca2+]i increased and declined was dependent upon
      the matrix protein on which the cells were plated but was generally complete
      within 1 hour from the time of plating. Calcium mobilization was found to be due
      to influx of calcium across the osteoblast plasma membrane and was integrin
      dependent. Carboxyamido triazole (CAI), a specific inhibitor of nonvoltage
      dependent calcium channels, or BAPTA-AM, a chelator of intracellular calcium,
      inhibited osteoblast adhesion and spreading on collagen type I, fibronectin and
      laminin in a dose-dependent manner. In conclusion, these results demonstrate that
      calcium mobilization is induced upon integrin-ligand contact and that calcium
      influx is required for cell adhesion and spreading.

PMID- 10908415
TI  - Na+/Ca2+ exchanger isoforms of rat odontoblasts and osteoblasts.
AB  - In odontoblasts as well as osteoblasts, a number of mechanisms for the inflow and
      extrusion of Ca2+ have been demonstrated. The entrance of Ca2+ ions into
      odontoblasts occurs mainly through voltage-gated calcium channels. Extrusion of
      Ca2+ is found to be an ATP-dependent process and, in addition, Na+/Ca2+-antiports
      exist, which are provoked by extracellular Na+. The aim of this study was to
      identify the Na+/Ca2+-antiport isoforms expressed in dentinogenically active rat
      incisor odontoblasts and to make a comparison with different osteoblastic cells.
      Using RT-PCR and RNAse protection assay, we demonstrated the expression of three
      different isoforms, NaCa 3, 7, and 10, of the NCX1-encoded antiport in
      odontoblasts and osteoblastic cells. When incubated in the presence of Na+,
      dissected rat incisor odontoblasts as well as the osteoblastic cells extruded
      Ca2+ ions, as detected by chlorotetracycline and Fura-2 fluorometry, thus
      supporting a physiological role for the detected isoform expression. Odontoblasts
      and rat calvarial osteoblasts, as well as osteoblast-like cell lines UMR-106.01
      and Saos-2, were shown to exhibit identical phenotypes of Na+/Ca2+-antiport
      isoform expression, different from the expression patterns of other tissues. The
      significance of this specific expression pattern is unknown, but there is a
      possibility that it is in some way related to the unique demands on these cell
      types to produce mineralized connective tissue.

PMID- 10908416
TI  - Effects of nicotine on bone and calciotropic hormones in growing female rats.
AB  - Limited research in young adults and immature animals suggests a detrimental
      effect of tobacco on bone during growth. This study investigated the effects of
      nicotine, the major alkaloid component of tobacco, on calciotropic hormone
      concentrations and bone status in growing female rats. One-month-old animals
      received either saline (n = 10), nicotine at 3.0 mg/kg/day (n = 10), or nicotine
      at 4.5 mg/kg/day (n = 10) administered subcutaneously via osmotic minipumps for
      either 2 or 3 months. Sera, femora, tibiae, and lumbar vertebrae (3-5) were
      collected at necropsy. The concentrations of serum calcium, phosphorus, 25
      hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, calcitonin, and
      insulin-like growth factor-I were determined. Bone variables evaluated included
      mineral content and density (vertebrae and femora), cancellous and cortical
      histomorphometry (tibiae), and bone strength (vertebrae and femora).
      Statistically significant differences in serum mineral and hormone concentrations
      were not associated with nicotine dose or exposure time. No significant nicotine
      treatment effects were detected for bone mineral content and density, bone
      histomorphometry, or bone strength. We conclude that nicotine treatment for 2 or
      3 months at serum concentrations in the upper range of those found in smokers has
      no detrimental effect on bone mass, volume, or strength in the growing rat.

PMID- 10908417
TI  - Osteoblast gene expression in rat long bones: effects of ovariectomy and
      dihydrotestosterone on mRNA levels.
AB  - The steroid sex hormones exert major effects on bone formation although the
      molecular events associated with their activity remain unclear. We have
      investigated the effects of ovariectomy and dihydrotestosterone (DHT)
      administration to both sham-operated and ovariectomized (ovx) rats on the bone
      mRNA levels of osteoblast genes. Rats were randomly allocated to either sham or
      ovariectomy operations and were administered either vehicle or 40 mg/ kg body
      weight DHT by silastic tube implants at the time of operation for 8 weeks, at
      which time they were killed and total RNA was extracted from the long bones.
      Northern blot analysis indicated that the mRNA levels of the bone cell genes
      alpha1(I) collagen, alkaline phosphatase, osteocalcin, and osteopontin were
      markedly increased in ovx rats between 6- and 30-fold. DHT administration to
      ovary-intact, estrogen-sufficient rats increased the mRNA levels of alpha1(I)
      collagen, alkaline phosphatase, osteopontin, and osteocalcin between 3- and 9
      fold. In contrast, DHT did not alter levels of these mRNA species in ovx rats.
      The data demonstrate that estrogen deficiency increased mRNA levels of genes
      expressed during osteoblast development and suggest an interplay between estrogen
      and androgen action in regulating the expression of a number of bone cell genes.

PMID- 10908418
TI  - Semi-quantitative fluorescence analysis of calcein binding as a measurement of in
      vitro mineralization.
AB  - We describe a new, highly sensitive semiquantitative method for rapid measurement
      of in vitro mineralization using calcein. Fluorescence analysis of the calcein
      bound to the calcium phosphate (hydroxyapatite) allows direct quantitation of
      extracellular matrix mineral content in monolayer cultures of bone-forming cells
      such as primary osteoblasts or osteosarcoma cells. Osteosarcoma cell lines UMR
      106 and SaOS-2 were used to demonstrate that qualitatively, calcein was bound to
      the same regions of the mineralized cell monolayer as seen by conventional
      histological staining with von Kossa or Alizarin Red S. Moreover, total bound
      calcein could be quantitated by direct fluorescence analysis using a Cytofluor II
      plate reader. Changes in cell monolayer calcein fluorescence were shown to
      correlate well with direct colorimetric measurement of acid-solubilized Ca+2 from
      parallel cultures. Relative mineral quantitation by calcein fluorescence is rapid
      and more sensitive than colorimetric Ca+2 assays, can be performed directly on
      unfixed or fixed cell monolayers, and does not require the use of radioisotopes.
      The cell monolayer remains intact and potentially available for further analysis.

PMID- 10908419
TI  - Prostaglandin E2 directly inhibits bone-resorbing activity of isolated mature
      osteoclasts mainly through the EP4 receptor.
AB  - Prostaglandins (PGs) are well known to be important local factors in regulating
      bone formation and resorption. PGE2 is a potent stimulator of bone resorption
      because of enhancing osteoclast formation by its indirect action through stromal
      cells. However, the direct action of PGE2 on functionally mature osteoclasts is
      still controversial. In this study using highly purified rabbit mature
      osteoclasts, we examined the direct effect of PGE2 on osteoclastic bone-resorbing
      activity and its mechanism. PGE2 inhibited resorption pit formation on a dentine
      slice by the purified osteoclasts in a dose- and time-dependent manner. The
      inhibitory effect appeared as early as 4 hours after the PGE2 addition. Forskolin
      and 12-0-tetradecanoyl phorbol-13-acetate (TPA), respective activators of
      adenylate cyclase and protein kinase C, also decreased the osteoclastic bone
      resorbing activity. PGE2 increased the content of intracellular cAMP in a dose
      range effective for the inhibition of bone resorption, whereas the prostanoid did
      not alter the intracellular level of inositol triphosphate. The inhibition of
      osteoclastic bone resorption by PGE2 was amplified and diminished by a cAMP
      phosphodiesterase inhibitor (isobutyl methylxanthine) and a protein kinase A
      inhibitor (Rp-cAMP), respectively. Of four different subtypes of PGE2 receptors
      (EPs), EP4 mRNA was predominantly expressed in isolated osteoclasts, whereas the
      other types of EP mRNA were detected in only small amounts. These results suggest
      that the PGE2 inhibitory effect was mediated by an adenylate cyclase system
      coupled with EP4. This possible association of PGE2 with EP4 in mature
      osteoclasts was supported by the finding that a specific agonist of EP4 (AE-604)
      inhibited the bone-resorbing activity and elevated the intracellular cAMP
      content. However, butaprost, a selective EP2 agonist, also mimicked the PGE2
      effects on isolated osteoclasts although EP2 mRNA expression was minimal. In
      conclusion, PGE2 directly inhibits bone-resorbing activity of functionally mature
      osteoclasts by activation of the adenylate cyclase system, perhaps mainly through
      EP4.

PMID- 10908421
TI  - European Calcified Tissue Society.

PMID- 10908420
TI  - Absence of correlation between BMP-4 polymorphism and postmenopausal osteoporosis
      in Italian women.
AB  - Several studies have demonstrated that bone has the power of regeneration and
      repair. BMPs (bone morphogenetic proteins) are involved in the determination of
      osteoblast phenotype and bone turnover, therefore genes coding for these
      proteins, like BMP-4, could be considered potential candidate genes for
      osteoporosis. We investigated the association of BMP-4 gene polymorphism with
      osteoporosis in a cohort of 72 osteoporotic, postmenopausal women and 82
      unrelated controls. We failed to detect any significant association between this
      genetic marker and the disease.

PMID- 10908422
TI  - Pantoprazole (Protonix).

PMID- 10908423
TI  - Gemtuzumab for relapsed acute myeloid leukemia.

PMID- 10908424
TI  - Human factors in telemedicine.

PMID- 10908425
TI  - Human factors in telesurgery: effects of time delay and asynchrony in video and
      control feedback with local manipulative assistance.
AB  - This paper presents the results of experiments examining the performance of a
      telesurgeon and an assistant local to the patient performing simulated
      laparoscopic tasks under a variety of time-delay conditions. Of particular
      interest is a comparison between the surgeon provided with audio/video and force
      feedbck synchronously with various time delays, and the surgeon performing
      asynchronously, where video is delayed relative to force feedback. These
      conditions are relevant since current telecommunication systems have limited
      bandwidth, and video signals must be compressed for efficient transmission. This
      produces a time lag between the video camera and the surgeon's monitor, Force
      feedback and position commands from a surgical teleoperator require much lower
      bandwidth, and can be transmitted in near-real time. In the first of two series
      of experiments, two laparoscopic training tasks were performed under different
      time-delay conditions, with force and video feedback delayed by equal amounts. In
      the second series, using the same tasks, the force feedback was more immediate,
      while the video delay lagged by the time required for compression and
      decompression. In both experiments, there were various role assignments in terms
      of whether the telesurgeon or the assistant controlled the laparoscope and/or the
      various surgical tools required. The three most striking results are that (1)
      nontrivial time delays significantly degraded the performance of the surgical
      tasks, (2) asynchronous force feedback resulted in significantly faster task
      performance than did synchronous performance when the surgeon operated the
      laparoscopic tools, and (3) there was no difference between synchrony and
      asynchrony when the remote surgeon operated the laparoscope and gave commands
      while the local assistant operated the surgical tools.

PMID- 10908426
TI  - Information acquisition from audio-video-data sources: an experimental study on
      remote diagnosis. The LOTAS Group.
AB  - OBJECTIVE: To determine what information sources are used during a remote
      diagnosis task. MATERIALS AND METHODS: Experienced trauma care providers viewed
      segments of videotaped initial trauma patient resuscitation and airway
      management. Experiment 1 collected responses from anesthesiologists to probing
      questions during and after the presentation of recorded video materials.
      Experiment 2 collected the responses from three types of care providers
      (anesthesiologists, nurses, and surgeons). Written and verbal responses were
      scored according to detection of critical events in video materials and
      categorized according to their content. Experiment 3 collected visual scanning
      data using an eyetracker during the viewing of recorded video materials from the
      three types of care providers. Eye-gaze data were analyzed in terms of focus on
      various parts of the videotaped materials. RESULTS: Care providers were found to
      be unable to detect several critical events. The three groups of subjects studied
      (anesthesiologists, nurses, and surgeons) focused on different aspects of
      videotaped materials. CONCLUSION: When the remote events and activities are
      multidisciplinary and rapidly changing, experts linked with audio-video-data
      connections may encounter difficulties in comprehending remote activities, and
      their information usage may be biased. Special training is needed for the remote
      decision-maker to appreciate tasks outside his or her speciality and beyond the
      boundaries of traditional divisions of labor.

PMID- 10908428
TI  - Challenges for user-interface designers of telemedicine systems.
AB  - Problems associated with telemedicine systems include high telecommunications
      costs, lack of physician interest, and failure to build evaluation into the
      design process from the onset of the telemedicine project. An overview of the
      human-factors engineering approach to systems design and how it can be applied to
      the development of telemedicine systems is described. Design of an interface is
      based on an analysis of user capabilities, tasks, and work environment. Task
      analyses are performed to understand and document the interaction between a
      user's work activities and a system. Two characteristics of a human factors
      approach that are important for telemedicine are: (1) defining and measuring user
      performance, and (2) involving users in the design and testing of a system.
      Usability goals are operationally defined and tracked to quantify performance.
      Having users participate in the design, testing, and critique of a system also
      increases the likelihood that the system will be accepted and used after it is
      released.

PMID- 10908427
TI  - Interactive telecardiology for the evaluation of heart murmurs in children.
AB  - OBJECTIVE: To study the accuracy, patient satisfaction, and cost of
      telecardiographic evaluations of pediatric patients. MATERIALS AND METHODS:
      Patients referred to a rural pediatric cardiology outreach clinic were examined
      in person by a pediatric cardiologist. A second pediatric cardiologist who had no
      knowledge of the findings of face-to-face examination reevaluated the same
      patients utilizing a 768-Kbps telemedicine system. Any additional testing was
      performed by personnel who had no knowledge of the face-to-face evaluation. The
      main outcome measures included the final cardiac diagnosis, frequency of
      additional tests such as electrocardiography, (ECG) echocardiography (ECHO), and
      patient satisfaction. RESULTS: The diagnosis was agreed upon in 19 of the 21
      patients studied. Two patients with small ventricular septal defects were missed
      during the telemedicine evaluation. The utilization rates of additional studies
      for both the face-to-face cardiologist and the telemedicine cardiologist were not
      significantly different. Patient satisfaction with the telemedicine encounter was
      good. CONCLUSIONS: Telemedicine appears to be effective and useful for the
      cardiac evaluation of pediatric patients. In spite of high data-transfer rates,
      differences between telemedicine and face-to-face patient encounters were
      observed.

PMID- 10908429
TI  - Aspects of human factors engineering in home telemedicine and telerehabilitation
      systems.
AB  - Human factors engineering and system design are critical elements in the newly
      developing field of telerehabilitation. Telerehabilitation is the remote delivery
      of rehabilitative services such as monitoring, training, and long-term care of
      persons with disabilities using telecommunications technology. This paper
      describes projects at the Rehabilitation Engineering Research Center (RERC) on
      Telerehabilitation in the context of three conceptual models: telecounseling and
      training, telemonitoring and assessment, and teletherapy. Issues pertaining to
      human factors engineering design are identified, and ongoing challenges are
      discussed.

PMID- 10908430
TI  - Heuristic evaluation of a web-based interface for internet telemedicine.
AB  - A low-cost usability engineering methodology (heuristic evaluation combined with
      small-scale expert assessment) is examined in the context of the design and
      development of a Web-based telemedicine system. Six experts - three human
      computer interaction (HCI) experts and three medical-content experts - examined
      the Spacebridge to Russia Web site for usability. The HCI experts identified 52
      interface problems using a set of ten usability criteria or heuristics; these
      problems ranged in severity from cosmetic to a major failure. The content experts
      completed a series of six simple tasks while describing their actions. The usage
      difficulties were related to the HCI problems identified and were primarily
      characterized by a mismatch of the designer model and the content expert model.
      This heuristic/usage methodology can provide an incremental benefit in a variety
      of other design activities. It is suggested herein that the combined
      heuristic/usage methodology should be included as a standard design component of
      dynamic telemedicine systems.

PMID- 10908431
TI  - The interactive surrogate travel system.
AB  - The Interactive Surrogate Travel (IST) system is based on the super-miniaturized
      system of virtual technology, Cave Automatic Virtual Environment (CAVE). Using
      bilateral virtual reality (VR-to-VR) communications, IST enables the testing of
      subjects via interactive communications. It appears that IST will find practical
      applications in the near future. We examined the utility of IST in medical
      treatment and psychiatric tests. Psychiatric symptoms reflect human pathos, which
      in turn are greatly influenced by culture. If these culture-bound symptoms can be
      adequately communicated between providers and clients of different cultures, we
      can develop effective telepsychiatric services across different societies and
      cultures. IST requires high-speed transmission and gigabyte circuits. A pilot
      project tested the utility of IST (through the use of optical fiber
      communications on earth) as a basis for experiments via the Gigabit satellite, to
      be launched in the year 2002.

PMID- 10908432
TI  - Developing a video-mediated communication system for hospitalized children.
AB  - When a student is away from school for an extended time due to illness, he/she is
      provided with a tutor or access to in-hospital classrooms to keep up with his/her
      studies. This isolates the child from normal classroom experiences. A remote
      control videoconferencing system (VCS), P.E.B.B.L.E.S.trade mark (Providing
      Education by Bringing Learning Environments to Students), was developed to allow
      a student access to his/her regular classroom from the hospital. Remote control
      is provided by a game pad, which allows the student to direct the system. The
      first iteration, P.E.B. B.L.E.S. I, tested feasibility. The design of
      P.E.B.B.L.E.S. II provides an integrated version of the system with user
      interface aimed at children. Four studies examined its efficacy in allowing a
      student to participate in typical classroom activities and in providing him/her a
      sense of presence in the classroom. Results indicate that the system can be used
      with relatively few errors when set to perform the majority of required
      activities. The study-participants reported positive experiences using the
      system, and remote users appeared to have a sense of presence in the classroom.

PMID- 10908433
TI  - A usability evaluation for telemedicine medical equipment.
AB  - This paper describes a conceptual framework and human factors evaluation for
      usability assessment of commercially available telemedicine technology. Four
      criteria of human factors evaluation are utilized: (1) technical acceptability;
      (2) operational effectiveness; (3) clinical appropriateness; and (4) equipment
      selection. These criteria were applied to commercially available video-otoscope
      systems for otological evaluations.

PMID- 10908434
TI  - The global forum on telemedicine: A bridge to the 21st century

PMID- 10908436
TI  - Cybermedicine: how computing empowers doctors and patients for better health care

PMID- 10908435
TI  - How to build a telemedicine system

PMID- 10908437
TI  - Diffusion of telemedicine: a knowledge barrier perspective.
AB  - Telemedicine, broadly defined as the use of information technology (IT) to
      deliver medical services over distances, is one proposed solution to problems of
      accessibility, quality, and costs of medical care. Although telemedicine
      applications have proliferated in recent years, their diffusion has remained low
      in terms of the volume of consultations. In this study, we extend Attewell's
      theory of knowledge barriers to explain why diffusion of telemedicine remains
      low. A longitudinal, embedded multiple case study of telemedicine programs in
      three medical centers in Boston, Massachusetts, reveals that, in addition to
      technical knowledge barriers, as suggested by Attewell, there are economic,
      organizational, and behavioral knowledge barriers that inhibit the diffusion of
      telemedicine. The lowering of these barriers entails intensive learning efforts
      by champions of applications within adopter organizations. They need to develop
      technically feasible, medically valid, reimbursable, and institutionally
      supported applications in order to justify the value of telemedicine and engender
      consistent and frequent use by physicians.

PMID- 10908438
TI  - The relative cost of outpatient telemedicine services.
AB  - OBJECTIVE: This study compares the costs of offering outpatient care to primarily
      orthopedic and dermatology patients via live, interactive telemedicine to the
      estimated costs of direct face-to-face care for the same patients. MATERIALS AND
      METHODS: A simple, yet detailed methodology was used to evaluate the cost of
      adding telemedicine to a health care delivery system, using a "hub-and-spoke"
      model located in Minnesota. The costs and cost savings of telemedicine were
      evaluated from the perspectives of patients, providers, insurers, employers, and
      society as a whole. Sensitivity analysis was used to investigate the impact of
      various factors on the model. RESULTS: The variable cost of a telemedicine
      referral was $144, versus an estimated face-to-face referral cost of $183.
      Reductions in patient travel costs and in lost employee productivity were the
      principal benefits of the system. The break-even point, where total costs equal
      total cost savings, equalled 1,449 consultations annually. Sensitivity analyses
      indicated that the breakeven point varies from a low of 152 telemedicine
      consultations for a "best case" scenario to no possible breakeven point for a
      "worst case" scenario. CONCLUSIONS: At the system's current level of 300
      consultations per year, the telemedicine system is estimated to add $45,000 to
      society's costs of providing medical care for these patients. The additional cost
      is primarily due to personnel expenses and an increase in the volume of specialty
      care. Patients see specialists more often due to improved access to care and
      lower transportation costs. Providers bear the cost while patients and employers
      enjoy substantial savings.

PMID- 10908439
TI  - Diagnostic accuracy and image quality using a digital camera for teledermatology.
AB  - OBJECTIVE: The study was designed to evaluate the effectiveness of digital
      photography for dermatologic diagnoses and compare it with in-person diagnoses.
      MATERIALS AND METHODS: Patients referred for specialty consultations (n = 308)
      were recruited from a university dermatology clinic. Patients were examined in
      person by one of three board-certified dermatologists who provided clinical
      diagnoses. Digital photos were obtained on all patients and were evaluated as
      computer images by a panel of dermatologists. RESULTS: There was 83% concordance
      between in-person versus digital photo diagnoses. Intradermatologist concordance
      averaged 84%, and interdermatologist concordance averaged 81%. Decision
      confidence was rated as "very definite" to "definite" 62% of the time.
      Concordance with biopsy results was achieved in 76% of the cases. Image sharpness
      and color quality were rated "good" to "excellent" 83% and 93% of the time,
      respectively. CONCLUSION: Digital photography for store-and-forward
      teledermatology produces high-quality images and diagnostic concordance rates
      that compare favorably with in-person clinical diagnoses.

PMID- 10908440
TI  - Efficiency analysis of a multi-specialty telemedicine service.
AB  - OBJECTIVE: The goal of this project was to assess case turn-around times for
      store-and-forward and real-time video consultations in the Arizona Telemedicine
      Program. MATERIALS AND METHODS: Five components contributing to total case turn
      around time were analyzed. Each parameter was submitted to statistical analysis
      and compared for store-and-forward and real-time sessions. RESULTS: Turn-around
      for real-time are longer than for store-and-forward sessions. Real-time sessions
      take longer, from when the consulting clinician is contacted to the time the case
      is reviewed. This is compounded by the fact that real-time sessions sometimes
      need to be rescheduled. For both types of consults, the time to deliver the final
      report is the longest segment of the total turn-around time. CONCLUSION: Several
      factors contribute to case turn-around times. By identifying and analyzing each
      contributing factor, it is possible to revise consult protocols to improve
      efficiency.

PMID- 10908441
TI  - Teleoncology in the Department of Defense: a tale of two systems.
AB  - Two telemedicine networks were developed for the purpose of conducting
      multidisciplinary oncology ("teleoncology") conferences. The infrastructure of
      each system differed: one system was Internet-based; the other was delivered via
      Integrated Services Digital Network (ISDN) lines. The purpose of this study was
      to describe the infrastructure and cost, consultative process, technical aspects,
      and conference format of the two teleoncology programs. The two systems'
      technical aspects, participant satisfaction with the systems, and conference
      participation were compared qualitatively. Assessment of the technical aspects of
      the systems suggested that each had distinct advantages. Survey results indicated
      that provider satisfaction with the technical and logistical aspects of each type
      of teleoncology conference was high. The present study may prove helpful for
      individuals who are considering implementing their own teleoncology programs.

PMID- 10908442
TI  - Telemedicine screening of glaucoma.
AB  - OBJECTIVES: Glaucoma is a major cause of blindness. More than 80,000 Americans
      suffer permanent vision loss from the disease. Widespread screening is
      fundamental in limiting the incidence of glaucoma-associated blindness. This
      pilot study explored the use of stereo digital images taken at a primary care
      center for telemedicine review by an off-site specialist as a means of screening
      for glaucoma. MATERIALS AND METHODS: Thirty-two diabetic patients were screened
      at a family medicine clinic. None had previously been diagnosed with glaucoma. A
      senior optometry student took stereoscopic digital and 35-mm optic disc
      photographs with a nonmydriatic retinal camera. The digital images were forwarded
      to a remote ophthalmologist for review. The conventional color stereo slide pairs
      of the same eyes were subsequently reviewed for comparison. Agreement on signs of
      glaucomatous disc changes between the two imaging systems was analyzed. RESULTS:
      Twenty-six of 32 eyes' digital and 35-mm photographs were analyzed. Six of 32
      eyes (18.8%) could not be compared due to lack of matching 35-mm slides or
      digital images. Out of 26 eyes, lamina cribosa visibility was undeterminable in 8
      eyes' digital images and 3 other eyes' 35-mm slides. Agreement among digital
      images and 35-mm slides of the remaining eyes was: 100%-vertical elongation,
      barring of vessels, bayoneting of vessels, and drance hemorrhage; 96.2%-focus
      notching of rim and rim pallor; 93.3%-lamina cribosa visability; 92. 3%-overpass
      cupping; 88.5%-focal enlargement; 84.6%-parapapillary halo; 80%-nerve fiber
      visibility; 65.4%-parapapillary atrophy. Parapapillary halo (p = 0.046) and nerve
      fiber layer visibility (p = 0.18) were detected on some 35-mm slides but not seen
      on matching digital views. CONCLUSION: Evaluations of cup-to-disc ratio (C/D)
      using both methods were in general agreement. However, some digital images were
      noted as too dark for assessing fine glaucomatous disc changes. Stereo digital
      images taken with a nonmydriatic camera by nonophthalmic photographers is a
      promising alternative for glaucoma screening in primary care settings.
      Telemedicine offers efficient communications with off-site glaucoma specialists.
      A larger study population is necessary to determine the overall effectiveness of
      using stereo digital imagery and teleophthalmology for glaucoma screening.

PMID- 10908443
TI  - Telemedicine to Iowa's correctional facilities: initial clinical experience and
      assessment of program costs.
AB  - OBJECTIVE: To evaluate the costs and benefits of a prison telemedicine program
      for the institutions involved and to assess early provider satisfaction.
      MATERIALS AND METHODS: A survey of primary care and consulting providers from
      four prisons and an academic tertiary care facility in Iowa was conducted during
      the first year of telemedicine service linked with the state's correctional
      facilities, from March, 1997 to February, 1998. Data were evaluated from 247
      completed telemedicine encounters. Cost estimates were made for (1) 1997 cost
      data for the 4,396 Iowa prisoners who were transported to The University of Iowa
      Hospitals and Clinics (UIHC) for their health care, and (2) the equipment,
      circuitry, and personnel costs necessary on both ends of the network to provide
      comparable telemedicine service to remote patients and providers. A formula for
      estimating the cost of implementing a telemedicine service is presented. It
      includes a projection for determining at what point the cost of the telemedicine
      visit approaches the average cost of an on-site visit (breakeven point). There
      was also a brief survey administered to presenting and consulting physicians to
      determine their overall satisfaction with the telemedicine system for diagnosis,
      treatment planning, and follow-up. RESULTS: The average cost to the prisons for
      an on-site inmate visit to the University of Iowa Hospitals and Clinics (UIHC)
      was $115 during our study period, from March 1997 to February 1998. Using a
      formula that specifies a number of fixed and variable costs for implementing
      telemedicine, we were able to determine that the breakeven point for Iowa's
      correctional facilities would require 275 teleconsultations per year, per site
      (total of 1,575 consultations a year). Given the higher equipment investment at
      the UIHC hub, the breakeven point would be around 2,000 teleconsultations
      annually. Cost studies did not include medical care, which is assumed to be
      relatively comparable for both on-site and telemedicine interactions. Overall,
      referring physicians expressed a higher rate of satisfaction with telemedicine
      than specialists (4.19 to 3.45, respectively, on a scale of 1 to 5 - 5
      representing the highest ranking). Both consulting and referring physicians
      ranked the quality of transmission the highest among all questions regarding
      satisfaction with the telemedicine system. CONCLUSIONS: No one should anticipate
      instantaneous cost-effectiveness with telemedicine. However, with careful
      planning, implementing a telemedicine program can be "cost-acceptable" initially.
      Telemedicine ultimately becomes cost-effective as the volume of teleconsults
      increases.

PMID- 10908444
TI  - The Global Health Network Supercourse: epidemiology, the internet, and global
      health.
AB  - BACKGROUND: The Global Health Network (GHNet) Supercourse is a collaboration
      project involving more than 750 professionals from 81 different countries aimed
      at developing a "library of lectures" related to epidemiology, the Internet, and
      global health. The goal of the Supercourse is to provide instructors of medical
      and other health related students with the best available information. RESULTS:
      The Supercourse is based on several concepts, including information-sharing,
      quality control, and global access. Currently, 80 lectures are available from
      scientists around the world. Each lecture serves as a "locator" with hypertext
      links to other pertinent information on the Internet. The British Medical Journal
      has put two textbooks on their Web site that interlace each lecture with links to
      specific pages or paragraphs of the books. All lectures are reviewed for quality
      by the global faculty and evaluated annually. Hence, lectures remain current,
      relevant, and of high quality. Mirrored sites of the Supercourse have been
      established to increase the accessibility of the Supercourse in areas of the
      world that may have limited connectivity. SUMMARY: While instructors are
      available worldwide, many do not have access to the latest health and prevention
      information, and many instructors would benefit from having the assistance of
      leading experts. Using an Internet-based lecture-shaping model for transnational
      training in public health, some of these teachers may be better equipped to train
      medical and health-related professionals.

PMID- 10908446
TI  - Handbook of telemedicine

PMID- 10908445
TI  - A store-forward ophthalmic telemedicine case report from deployed U. S. Army
      forces in Kuwait.
AB  - This telemedicine test was developed to determine the relative ease with which an
      off-the-shelf ophthalmic telemedicine package could be successfully applied from
      within a remote theatre of operations. The project was conducted at the Camp Doha
      Health Clinic, located just outside Kuwait City, during the period from April
      12(th) through April 23(rd), 1998. The deployed signal unit had contracted for a
      direct T-1 commercial satellite link (via MCI), which allowed for direct internet
      connectivity using a PCMCIA network card. Digital images were sent via this
      connection to 140 e-mail sites throughout the world, including an unsolicited
      image to each of 134 Army optometry officers for their review, analysis, and
      diagnosis. Return responses to this unsolicited survey were 53 out of 134, for a
      39.7% response rate. Half of the respondents were able to view the image with
      ease and clarity, rendering an accurate clinical diagnosis. The other half of the
      respondents either did not have the software to display an image on their
      clinical desktop PC, or did not know how to use their provided software. This
      project clearly indicates that an off-the-shelf ophthalmic digital system can be
      successfully used from a remote deployed site. However, the consulting clinicians
      require up-to-date training, and their computer packages should have as wide a
      capability base as possible.

PMID- 10908447
TI  - A uniform format for ocular imaging devices.
AB  - PURPOSE: To develop a uniform file format of ocular imaging data, including, but
      not limited to, ultrasound biomicroscopy, optical coherence tomography, and nerve
      fiber analyzer, capable of being transmitted via Internet or intranet for
      collaborative research and telemedicine use. METHOD: File filters were developed
      as dynamic link libraries (DLLs). These can read the original raw data format of
      each ocular imaging device. A data file format was also designed to describe
      these raw data uniformly in three different types of compression: noncompressed,
      run length compression, and differential pulse code modulation (DPCM). These
      three file formats were then tested in the following aspects: file size, speed of
      reading, and speed of writing. RESULTS: Run length compression failed to compress
      raw data, while DPCM compressed raw data successfully (< or =35.5%). The speed of
      reading and writing files was slowest in DPCM. However, the actual time of
      reading and writing was fast enough (<0.6 s) for daily work regardless of file
      compression methods. CONCLUSION: The format designed has robust potential to be
      the standard file format for transmission of any ocular imaging raw data.

PMID- 10908448
TI  - Routine surgical telepathology in the Department of Veterans Affairs: experience
      related improvements in pathologist performance in 2200 cases.
AB  - OBJECTIVE: To determine whether diagnostic concordance, case deferral rate,
      and/or time required to review slides changed significantly as telepathologists
      gained additional experience using a hybrid dynamic/store-and-forward (HDSF)
      telepathology (TP) system on the 2000 cases following an initial 200 consecutive
      surgical cases, previously reported. MATERIALS AND METHODS: Gross surgical
      pathology specimens were prepared by specially trained personnel in Iron
      Mountain, Michigan. For TP, glass slides were placed on the stage of a robotic
      microscope at the Iron Mountain VAMC (remote site); control of the motorized
      microscope was then transferred to a pathologist located 220 miles away at the
      Milwaukee, Wisconsin, VAMC (host site). For each case, a telepathologist had the
      option of either rendering a diagnosis or deferring the case for later analysis
      by conventional light microscopy (LM). After the slides were read by TP and a
      surgical pathology report had been generated (for nondeferred cases), the slides
      were transported to Milwaukee, where they were reexamined by the same
      pathologist, now using LM. When there was disagreement between the TP and LM
      diagnosis, a supplemental or revised report was issued, and the referring
      physician was notified by telephone immediately. All supplemental and revised
      reports were reviewed by a third pathologist in the group. The slides were then
      reviewed by the pathology group practice or, when there was no consensus, by the
      Armed Forces Institute of Pathology to establish a "truth" diagnosis. To
      determine changes in telepathologist performance with experience after the
      initial start-up of the service, their performance in handling 10 consecutive
      sets of 200 surgical pathology cases was analyzed. RESULTS: Concordance rates for
      clinically significant TP and LM diagnoses were high for all 10 sets, ranging
      from 99% to 100%. Comparing the first set (Cases 201-400) with the last set
      (Cases 2001-2200), viewing times per case were reduced from 10.26 min to 3. 58
      min. Viewing times per slide were reduced from 3.44 min to 1.13 min per slide,
      comparing the first and last sets. Case turnaround times (TAT) decreased from
      2.46 days to < or =1.5 days. CONCLUSION: Thes results demonstrate that
      improvements in TP services occur over time as the result of additional
      experience using the TP system. The high diagnostic concordance and low rate of
      case deferral lend additional support to the proposal that a host-site
      pathologist using HDSF TP can substitute effectively for an on-site pathologist
      as a service provider.

PMID- 10908449
TI  - Live transmission of neonatal echocardiograms from underserved areas: accuracy,
      patient care, and cost.
AB  - OBJECTIVE: Echocardiography is an important tool in the diagnosis and management
      of critically ill neonates. The authors hypothesized that live telemedicine
      guidance and interpretation of neonatal echocardiograms from underserved areas
      would improve management, prevent unnecessary transports, enhance sonographer
      proficiency, and result in monetary savings. MATERIALS AND METHODS: Using
      personal computers capable of real-time transmission of echocardiograms over
      three integrated services digital network (ISDN) telephone lines, pediatric
      cardiologists interpreted echocardiograms, suggested views to sonographers, and
      made recommendations to neonatologists 200 miles away. Analyses of accuracy,
      management, echocardiogram quality, time, and costs were carried out
      prospectively. RESULTS: Sixty studies were transmitted over 7 months. Indications
      for echocardiography were suspected congenital heart disease (n = 29), suspected
      patent ductus arteriosus (PDA) (n = 27), and hemodynamic instability (n = 4).
      Diagnoses were critical congenital heart disease (n = 4), noncritical heart
      disease (n = 8), PDA (n = 21), ventricular dysfunction (n = 5), persistent
      pulmonary hypertension (n = 3), and normal (n = 19). Videotape review confirmed
      all telemedicine interpretations. The echocardiogram led to immediate change in
      management in 25 cases (42%), and echocardiogram quality was improved in 53
      studies (88%). Time from request to completion of echocardiography was 43+/-30
      min. Monetary savings from five avoided transports exceeded all expenses.
      CONCLUSION: Live transmission of neonatal echocardiograms over three ISDN lines
      is diagnostic, improves patient care and echocardiography quality, and is cost
      effective.

PMID- 10908450
TI  - Sickle cell telemedicine and standard clinical encounters: a comparison of
      patient satisfaction.
AB  - OBJECTIVES: To determine patient satisfaction with telemedicine encounters among
      adults with sickle cell disease and compare their scores with SCD patients who
      have standard medical encounters (as controls). METHODS: Adults patients were
      recruited from a list of participants in sickle cell telemedicine clinics and
      prospectively at the time of clinic encounter. Patients were assigned to
      telemedicine or standard encounter groups. Demographic and pertinent clinical
      data were obtained for all subjects, and the Client Satisfaction Questionnaire
      (CSQ-8) was administered. Patients were also asked for open-ended comments
      regarding their satisfaction with the service. Their responses were recorded
      verbatim. RESULTS: Patients with telemedicine (n = 60) and standard encounters (n
      = 60) were comparable in gender, genotype, education, employment, and mean number
      of sickle cell disease-related complications. Patients in the telemedicine group
      were younger (p< 0.005), more likely to have Medicaid insurance (p = 0.009), and
      more likely be taking hydroxyurea (p = 0.003) than patients in the control
      encounter group. Mean CSQ scores for the telemedicine group were high (total:
      28.82+/-3.06), and there was no difference for any item between encounter groups
      (p = 0.389). Patients in the standard encounter group were more likely to provide
      positive open-ended comments regarding the encounter (95% vs. 70%; p = 0.001).
      Negative comments were generally in the area of confidentiality. CONCLUSIONS:
      While some patients expressed concern about confidentiality with telemedicine,
      the benefits of improved access and continuity of care were recognized, and
      overall satisfaction with telemedicine was high. These findings support the use
      of telemedicine as an acceptable health care delivery option for rural,
      underserved populations with sickle cell disease.

PMID- 10908451
TI  - Teledermatology in a capitated delivery system using distributed information
      architecture: design and development.
AB  - OBJECTIVE: This report describes the design, development, and technical
      evaluation of a teledermatology system utilizing digital images and electronic
      forms captured through, stored on, and viewed through a common web server in an
      urban capitated delivery system. MATERIALS AND METHODS: The authors designed a
      system whereby a primary care physician was able to seek a dermatologic
      consultation electronically, provide the specialist with digital images acquired
      according to a standardized protocol, and review the specialist response within 2
      business days of the request. The settings were two primary care practices in
      eastern Massachusetts that were affiliated with a large integrated delivery
      system. Technical evaluation of the effectiveness of the system involved 18
      patients. Main outcome measures included physician and patient satisfaction and
      comfort and efficiency of care delivery. RESULTS: In 15 cases, the consultant
      dermatologist was comfortable in providing definitive diagnosis and treatment
      recommendations. In 3 cases, additional information (laboratory studies or more
      history) was requested. There were no instances where the dermatologist felt that
      a face-to-face visit was necessary. CONCLUSIONS: This novel approach shows
      promise for the delivery of specialist expertise via the internet. Cost
      effectiveness studies may be necessary for more widespread implementation.

PMID- 10908452
TI  - Telepathology between Richmond and Beckley Veterans Affairs Hospitals: report on
      the first 1000 cases.
AB  - OBJECTIVE: A telepathology connection between Richmond VAMC and Beckley VAMC
      using dynamic robotic telepathology to provide pathology services remotely was
      established. MATERIALS AND METHODS: This study reports a 14-month experience
      using telepathology to diagnose surgical specimens obtained from patients at the
      Beckley VA Medical Center and viewed in Richmond 250 miles away. Over 14 months,
      2325 slides representing 1000 cases were viewed. RESULTS: Discrepancies were
      observed in 20 of 2325 slides, or 0.86% of the total. None of the patients, where
      a discrepancy was found, were adversely affected by the preliminary report given.
      CONCLUSIONS: This study demonstrates that telepathology is a reliable and cost
      effective alternative to on-site pathology services and reviews advantages and
      disadvantages of the system.

PMID- 10908453
TI  - The effect of decreasing digital image resolution on teledermatology diagnosis.
AB  - OBJECTIVE: To determine the effect of degraded digital image resolution (as
      viewed on a monitor) on the accuracy and confidence of dermatologic
      interpretation. MATERIALS AND METHODS: Eight dermatologists interpreted 180
      clinical cases divided into three Logical Competitor Sets (LCS) (pigmented
      lesions, non-pigmented lesions, and inflammatory dermatoses). Each case was
      digitized at three different resolutions. The images were randomized and divided
      into (9) 60-image sessions. The physicians were completely blinded concerning the
      image resolution. After 60 seconds per image, the viewer recorded a diagnosis and
      level of confidence. The resultant ROC curves compared the effect of LCS, level
      of clinical difficulty, and resolution of the digital image. One-way analysis of
      variance (ANOVA) compared the curves. RESULTS: The areas beneath the ROC curves
      did not demonstrate any consistently significant difference between the digital
      image resolutions for all LCS and levels of difficulty. The only significant
      effect observed was amongst pigmented lesions (LCS-A) where the ROC curve area
      was significantly smaller in the easy images at high resolution compared to low
      and medium resolutions. For all other ROC curve comparisons within LCS-A, at all
      other levels of difficulty, as well as within the other LCS at all levels of
      difficulty, none of the differences was significant. CONCLUSION: A 720 x 500
      pixel image can be considered equivalent to a 1490 x 1000 pixel image for most
      store-and-forward teledermatology consultations.

PMID- 10908454
TI  - A compression and transmission system of ultrasonic image sequence for
      telemedicine.
AB  - OBJECTIVE: A newly developed compression and transmission system of ultrasound
      image sequence for telemedicine is proposed for transmitting ultrasonic image
      sequence in real time via IP-connected computers for telemedicine. MATERIALS AND
      METHODS: In the compression method, the characteristics of ultrasound images were
      taken into account. Only sound data were essential, and the histogram of the
      images had two narrow distributions around black-and-white areas. The sound data,
      therefore, were run length encoded and then transmitted. In the transmission,
      UDP/IP was employed with a time weight insertion among the packets so as not to
      overflow the data buffers of computers in this system to derive the maximum
      transmission performance up to the network capacity. The decompression method was
      the same as the generation of the sector scan images from the sound data, so that
      natural ultrasound image sequence could be obtained. RESULTS: This system was
      evaluated by transmitting the ultrasonic image sequence of the heart via ISDN (1.
      5 mbps). Although this system completely specialized in compression and
      transmission of the ultrasound sector scan image sequence, a relatively good
      performance in the frame rate and the image quality was achieved, compared with
      the previous systems (H.260, JPEG, and MPEG-1).

PMID- 10908455
TI  - Clinical feasibility of remote angiographic teleconsultation using a ISDN-30
      communication network.

PMID- 10908456
TI  - Application development approach based on space technology.
AB  - This paper introduces the activities of the National Space Development Agency of
      Japan (NASDA), focusing the activities of its newly established division of the
      Satellite Mission Application Center. The major objective of the center is to
      further promote the utilization of the space-based technologies and the creation
      of new satellite missions. The center is exploring future cooperative activities
      that may work with countries in Asia and the Pacific. The application of
      satellite communications for the field of telemedicine is one of its potential
      activity areas.

PMID- 10908457
TI  - Active versus expectant management in the third stage of labour.
AB  - BACKGROUND: Expectant management of the third stage of labour involves allowing
      the placenta to deliver spontaneously or aiding by gravity or nipple stimulation.
      Active management involves administration of a prophylactic oxytocic before
      delivery of the placenta, and usually early cord clamping and cutting, and
      controlled cord traction of the umbilical cord. OBJECTIVES: The objective of this
      review was to assess the effects of active versus expectant management on blood
      loss, post partum haemorrhage and other maternal and perinatal complications of
      the third stage of labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy
      and Childbirth Group trials register. SELECTION CRITERIA: Randomised trials
      comparing active and expectant management of the third stage of labour in women
      who were expecting a vaginal delivery. DATA COLLECTION AND ANALYSIS: Trial
      quality was assessed and data were extracted independently by the reviewers. MAIN
      RESULTS: Five studies were included. Four of the trials were of good quality.
      Compared to expectant management, active management (in the setting of a
      maternity hospital) was associated with the following reduced risks: maternal
      blood loss (weighted mean difference -79.33 millilitres, 95% confidence interval 
      94.29 to -64.37); post partum haemorrhage of more than 500 millilitres (relative
      risk 0.38, 95% confidence interval 0.32 to 0.46); prolonged third stage of labour
      (weighted mean difference -9.77 minutes, 95% confidence interval -10.00 to -9.
      53). Active management was associated with an increased risk of maternal nausea
      (relative risk 1.95, 95% confidence interval 1.58 to 2.42), vomiting and raised
      blood pressure (probably due to the use of ergometrine). No advantages or
      disadvantages were apparent for the baby. REVIEWER'S CONCLUSIONS: Routine 'active
      management' is superior to 'expectant management' in terms of blood loss, post
      partum haemorrhage and other serious complications of the third stage of labour.
      Active management is, however, associated with an increased risk of unpleasant
      side effects (eg nausea and vomiting), and hypertension, where ergometrine is
      used. Active management should be the routine management of choice for women
      expecting to deliver a baby by vaginal delivery in a maternity hospital. The
      implications are less clear for other settings including domiciliary practice (in
      developing and industrialised countries).

PMID- 10908458
TI  - Cephalic version by postural management for breech presentation.
AB  - BACKGROUND: It is possible that maternal posture may influence fetal position.
      Many postural techniques have been used to promote cephalic version. OBJECTIVES:
      The objective of this review was to assess the effects of postural management of
      breech presentation on measures of pregnancy outcome. SEARCH STRATEGY: The
      Cochrane Pregnancy and Childbirth trials register and Controlled Trials Register
      were searched. Date of last search: March 2000. SELECTION CRITERIA: Randomised
      and quasi-randomised trials comparing postural management with pelvic elevation
      for breech presentation, with a control group. DATA COLLECTION AND ANALYSIS:
      Eligibility and trial quality were assessed by one or both reviewers. MAIN
      RESULTS: Five studies involving a total of 392 women were included. No effect of
      postural management on the rate non-cephalic births was detected, either for the
      subgroup in which no external cephalic version was attempted, or for the group
      overall (relative risk 0.95, 95% confidence interval 0.81 to 1.11). No
      differences were detected for caesarean sections or Apgar scores below seven at
      one minute. REVIEWER'S CONCLUSIONS: There is no evidence to support the use of
      postural management for breech presentation. The numbers of women studied to date
      remain relatively small.

PMID- 10908459
TI  - Clomiphene citrate for unexplained subfertility in women.
AB  - BACKGROUND: The effectiveness of clomiphene citrate has been clearly demonstrated
      in the treatment of sub-fertility associated with oligo-ovulation. The multiple
      pregnancy rate associated with clomiphene, however, is elevated at approximately
      10%. Additional side effects associated with clomiphene use also include hot
      flashes, mood swings, headaches and visual disturbances. A variety of
      publications have raised the question of increased ovarian cancer risks
      associated with clomiphene use. Understanding the effectiveness of clomiphene in
      this patient group is therefore, extremely important. OBJECTIVES: To determine
      the effectiveness of clomiphene citrate given to women with unexplained
      subfertility, in a dose range of 50-250 mg for up to 10 days. The primary outcome
      was clinical pregnancy. SEARCH STRATEGY: RCTs were identified using the search
      strategies developed for the menstrual disorders and subfertility group. See
      review group for more information. SELECTION CRITERIA: Randomized controlled
      trials were included if they were relevant to the clinical question posed and
      reported data in treated and untreated groups. Cohort studies were excluded. DATA
      COLLECTION AND ANALYSIS: Eleven potentially relevant trials were identified, of
      which six were included in this review. All trials were assessed for quality in
      terms of method of randomization, completeness of follow up, presence or absence
      of cross-over and co-intervention. MAIN RESULTS: Clomiphene appeared to be
      superior to no treatment or placebo. The common odds ratios for clinical
      pregnancy per patient and per treatment cycle were 2.37 (1.22-4.62) and 2.5 (1.35
      4.62) respectively. Although there was some clinical heterogeneity between
      studies, the results were statistically homogeneous (p>0.1). These data suggest
      statistically and clinically significant improvement in pregnancy rate following
      clomiphene citrate in women with unexplained infertility. REVIEWER'S CONCLUSIONS:
      Although the absolute treatment effect is small, given the low cost and ease of
      administration, clomiphene citrate appears to be a sensible first choice
      treatment for women with unexplained infertility. However, in making this
      treatment choice, concerns of long-term use and ovarian cancer risk, multiple
      pregnancy risk and minor symptoms should be discussed. Given the extensive use of
      clomiphene in ovulatory women and recent concerns associated with long term use,
      a definitive trial with adequate power is warranted to establish effectiveness in
      women with unexplained subfertility.

PMID- 10908460
TI  - Mefloquine for preventing malaria in non-immune adult travellers.
AB  - BACKGROUND: Mefloquine is a commonly prescribed antimalarial drug which has now
      largely replaced earlier malaria chemoprophylaxis, since increasing parasite
      resistance has meant that these earlier drugs are no longer considered to be
      effective against all Plasmodium species. However mefloquine may be associated
      with neuropsychiatric harmful effects. OBJECTIVES: The objective of this review
      was to assess the effects of mefloquine in adult travellers. SEARCH STRATEGY: We
      searched the Cochrane Infectious Diseases Group trials register, MEDLINE, EMBASE,
      Lilacs, Science Citation Index and reference lists of articles. We contacted
      researchers in the subject of malaria chemoprophylaxis, and drug companies.
      SELECTION CRITERIA: Randomised trials comparing mefloquine with other standard
      prophylaxis or placebo in non-immune adult travellers, and in non-travelling
      volunteers. We compiled and included in the review a database of published case
      reports of mefloquine adverse effects. DATA COLLECTION AND ANALYSIS: We
      independently assessed trial quality and extracted data. We also contacted study
      authors. MAIN RESULTS: We included 10 trials involving 2750 non-immune adult
      participants. Five of these were field trials, and of these all were in soldiers.
      One trial comparing mefloquine with placebo showed mefloquine prevented malaria
      episodes in an area of drug resistance (odds ratio 0.04, 95% confidence interval
      0.02 to 0.08). Withdrawals in the mefloquine group were consistently higher in
      four placebo controlled trials (odds ratio 3.56, 95% confidence interval 1.67 to
      7.60). In five trials comparing mefloquine with other chemoprophylaxis, no
      difference in tolerability was detected. We found 519 published case reports of
      mefloquine adverse effects. 71 per cent of these published reports involved
      tourists and business travellers. REVIEWER'S CONCLUSIONS: Mefloquine prevents
      malaria, but there is not enough evidence to evaluate its tolerability in non
      military travellers. There is evidence from non-randomised studies that
      mefloquine is a potentially harmful drug for tourists and business travellers,
      needing more careful evaluation. A randomised tolerability study is urgently
      needed in these groups.

PMID- 10908461
TI  - Nasal continuous positive airways pressure immediately after extubation for
      preventing morbidity in preterm infants.
AB  - BACKGROUND: Preterm infants being extubated following a period of intermittent
      positive pressure ventilation via an endotracheal tube are at risk of developing
      respiratory failure as a result of apnea, respiratory acidosis and hypoxia. Nasal
      continuous positive airway pressure appears to stabilise the upper airway,
      improve lung function and reduce apnea and may therefore have a role in
      facilitating extubation in this population. OBJECTIVES: In preterm infants having
      their endotracheal tube removed following a period of intermittent positive
      pressure ventilation (IPPV), does management with nasal continuous positive
      airways pressure (NCPAP) lead to an increased proportion remaining free of
      additional ventilatory support, compared to extubation directly to headbox
      oxygen? SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal
      Trials, Medline, previous reviews including cross references, abstracts of
      conferences and symposia proceedings, expert informants, journal handsearching
      mainly in the English language and expert informant searches in the Japanese
      language by Prof. Ogawa. SELECTION CRITERIA: All trials utilising random or quasi
      random patient allocation, in which NCPAP (delivered by any method) was compared
      with headbox oxygen for post-extubation care were included. Methodological
      quality was assessed independently by the two authors. DATA COLLECTION AND
      ANALYSIS: Data were extracted independently by the two authors. Prespecified
      subgroup analysis to determine the impact of different levels of NCPAP,
      differences in duration of IPPV and use of aminophylline were also performed
      using the same package. Data were analysed using relative risk (RR), risk
      difference (RD) and number needed to treat (NNT). MAIN RESULTS: Nasal CPAP, when
      applied to preterm infants being extubated following IPPV, reduces the incidence
      of adverse clinical events (apnea, respiratory acidosis and increased oxygen
      requirements) indicating the need for additional ventilatory support [RR 0.62
      (0.49, 0.79), RD -0.175 (-0. 256,-0.095), NNT 6 (4,11)]. A trend towards
      reduction in the incidence of chronic lung disease at 28 days of age is also seen
      in the group extubated to NCPAP. This does not reach statistical significance [RR
      0.86 (0.67,1.10), RD -0.069 (-0.177,0.039)]. REVIEWER'S CONCLUSIONS: 
      IMPLICATIONS FOR PRACTICE: nasal CPAP is effective in preventing failure of
      extubation in preterm infants following a period of endotracheal intubation and
      IPPV. Implication for research: further definition of the gestational age and
      weight groups in whom these results apply is required. Optimal levels of NCPAP as
      well as methods of administration remain to be determined.

PMID- 10908462
TI  - Nicotine replacement therapy for smoking cessation.
AB  - BACKGROUND: The aim of nicotine replacement therapy (NRT) is to replace nicotine
      from cigarettes. This reduces withdrawal symptoms associated with smoking
      cessation thus helping resist the urge to smoke cigarettes. OBJECTIVES: The aims
      of this review were to determine the effectiveness of the different forms of
      nicotine replacement therapy (chewing gum, transdermal patches, nasal spray,
      inhalers and tablets) in achieving abstinence from cigarettes; to determine
      whether the effect is influenced by the clinical setting in which the smoker is
      recruited and treated, the dosage and form of the NRT used, or the intensity of
      additional advice and support offered to the smoker; to determine whether
      combinations of NRT are more effective than one type alone; and to determine its
      effectiveness compared to other pharmacotherapies. SEARCH STRATEGY: We searched
      the Cochrane Tobacco Addiction Group trials register in April 2000. SELECTION
      CRITERIA: Randomized trials in which NRT was compared to placebo or no treatment,
      or where different doses of NRT were compared. We excluded trials which did not
      report cessation rates, and those with follow-up of less than six months. DATA
      COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of subjects,
      the dose and duration and form of nicotine therapy, the outcome measures, method
      of randomisation, and completeness of follow-up. The main outcome measure was
      abstinence from smoking after at least six months of follow-up. We used the most
      rigorous definition of abstinence for each trial, and biochemically validated
      rates if available. Where appropriate, we performed meta-analysis using a fixed
      effects model. MAIN RESULTS: We identified one hundred trials; of the 88 with a
      non NRT control group, 48 trials were of nicotine gum, 30 of transdermal nicotine
      patch, four of intranasal nicotine spray, four of inhaled nicotine and two of
      nicotine sublingual tablet. Four trials compared combinations of two forms of
      nicotine therapy with one form alone. The odds ratio for abstinence with NRT
      compared to control was 1.71 (95% confidence interval 1.60 to 1.82), The odds
      ratios for the different forms of NRT were 1.63 for gum, 1.73 for patches, 2.27
      for nasal spray, 2.08 for inhaled nicotine and 1.73 for nicotine sublingual
      tablet. These odds were largely independent of the intensity of additional
      support provided or the setting in which the NRT was offered. Eight weeks of
      patch therapy was as effective as longer courses and there was no evidence that
      tapered therapy was better than abrupt withdrawal. Wearing the patch only during
      waking hours (16 hours/day) was as effective as wearing it for 24 hours/day. The
      odds ratio for abstinence in the trials which directly compared 4 mg versus 2 mg
      gum in highly dependent smokers found a significant benefit in favour of 4 mg gum
      (odds ratio 2.67, 95% confidence interval 1.69 to 4.22). There is no strong
      evidence that combinations of forms of NRT are more effective. Only one study
      directly compared NRT to an antidepressant (bupropion). In this study, bupropion
      was significantly more effective than nicotine patch or placebo. The combination
      of bupropion and nicotine patch was significantly more effective than nicotine
      patch alone. There was also a suggestion of greater of efficacy for bupropion and
      nicotine patch compared to bupropion alone, but the difference was not
      statistically significant. REVIEWER'S CONCLUSIONS: All of the commercially
      available forms of NRT (nicotine gum, transdermal patch, the nicotine nasal
      spray, nicotine inhaler and nicotine sublingual tablets) are effective as part of
      a strategy to promote smoking cessation. They increase quit rates approximately
      1.5 to 2 fold regardless of setting. The effectiveness of NRT appears to be
      largely independent of the intensity of additional support provided to the
      smoker. Since all the trials of NRT reported so far have included at least some
      form of brief advice to the smoker, this represents the minimum which should be
      offered in order to ensure its effectiveness. Provision of more intense levels of
      support, although beneficial in facilitating the likelihood of quitting, is not
      essential to the success of NRT. There is promising evidence that bupropion may
      be more effective than NRT (either alone or in combination). However, its most
      appropriate place in the therapeutic armamentarium requires further study and
      consideration.

PMID- 10908463
TI  - Tacrine for Alzheimer's disease.
AB  - OBJECTIVES: To determine the clinical efficacy of tacrine for the symptoms of
      Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia Group Register of
      Clinical Trials was searched using the terms 'tacrine', 'tetrahydroaminoacridine'
      and 'THA' (see the Group's search strategy for full details). SELECTION CRITERIA:
      All unconfounded, double-blind, randomized trials in which treatment with tacrine
      was administered for more than a day and compared to placebo in patients with
      dementia of the Alzheimer's type. DATA COLLECTION AND ANALYSIS: Data were
      extracted independently by two reviewers, pooled if appropriate and possible, and
      the pooled odds ratios (95%CI) or the average differences (95%CI) were estimated.
      Where possible, intention-to-treat data were used. MAIN RESULTS: This review
      produced no clear results. The results were compatible with tacrine producing
      improvement, no change or even harm for those with Alzheimer's disease. It was
      not possible to use many of the published results in a combined analysis. For
      measures of overall clinical improvement, the intention-to-treat analyses failed
      to detect any difference between tacrine and placebo (OR 0.87; 95%CI 0. 61 -
      1.23). Behavioural disturbance, as measured by the Alzheimer's Disease Assessment
      Scale-noncognitive, failed to detect any difference between tacrine and placebo
      (SMD -0.04; 95%CI -0.52 - 0. 43). For cognition function, the effect of tacrine
      was not statistically significantly different from placebo for the MiniMental
      State Examination score (0-30; high =good) (SMD 0.14; 95%CI -0.02 - 0.30) and was
      barely statistically significantly in favour of treatment for the Alzheimer's
      Disease Assessment Scale-cognitive scale (SMD -0.22; 95%CI -0.32 - -0.13).
      Adverse events were not reported in a systematic way in the different trials,
      making formal comparison difficult. Raised serum liver enzymes was the major
      reason for withdrawal. The odds ratio for withdrawal due to an adverse event was
      significantly different from one, the control group experienced fewer events (OR
      5.7; 95%CI 4.1-7.9). Gastrointestinal side effects (diarrhoea, anorexia,
      dyspepsia and abdominal pain) were the other major cause of adverse events and
      for withdrawal, and the odds ratio for withdrawal was also significantly
      different from one in favour of the control group (OR 3.8; 95%CI 2. 8-5.1). No
      deaths were reported in any of the studies during the trial period, up to six
      months. REVIEWER'S CONCLUSIONS: This review provides no convincing evidence that
      tacrine is a useful treatment for the symptoms of Alzheimer's disease. However,
      as so few trials presented data in a format suitable for pooling, the results of
      this review may be modified when further data from all relevant trials are
      included. There is an urgent need for the independent evaluation of the data
      already existing in the trials but not accessible through published or grouped
      data. An independent meta-analysis of the individual-patient data is required.
      The results and conclusions of this update are unaltered by further searching as
      the additional studies do not add any further valid/eligible data.

PMID- 10908464
TI  - Interventions for psoriatic arthritis.
AB  - OBJECTIVES: To assess the effects of salazopyrin, auranofin, etretinate, fumaric
      acid, IMI gold, azathioprine, efamol marine and methotrexate, in psoriatic
      arthritis. SEARCH STRATEGY: We searched Medline up to February 2000, and Excerpta
      Medica (June 1974-95). Search terms were psoriasis, arthritis, therapy and/or
      controlled trial. This was supplemented by manually searching bibliographies of
      previously published reviews, conference proceedings, contacting drug companies
      and referring to the Cochrane Clinical Trials Register. All languages were
      included in the initial search. SELECTION CRITERIA: All randomized trials
      comparing salazopyrin, auranofin, etretinate, fumaric acid, IMI gold,
      azathioprine, and methotrexate, in psoriatic arthritis. Following a published a
      priori protocol, the main outcome measures included individual component
      variables derived from Outcome Measures in Rheumatology Clinical Trials
      (OMERACT). These include acute phase reactants, disability, pain, patient global
      assessment, physician global assessment, swollen joint count, tender joint count
      and radiographic changes of joints in any trial of one year or longer [Tugwell
      1993], and the change in pooled disease index (DI). Only English trials were
      included in the review. DATA COLLECTION AND ANALYSIS: Data were independently
      extracted from the published reports by two of the reviewers (MC, GJ). An
      independent blinded quality assessment was also performed. MAIN RESULTS: Twenty
      randomized trials were identified of which thirteen were included in the
      quantitative analysis with data from 1022 subjects. Although all agents were
      better than placebo, parenteral high dose methotrexate (not included),
      salazopyrin, azathioprine and etretinate were the agents that achieved
      statistical significance in a global index of disease activity (although it
      should be noted that only one component variable was available for azathioprine
      and only one trial was available for etretinate suggesting some caution is
      necessary in interpreting these results). Analysis of response in individual
      disease activity markers was more variable with considerable differences between
      different medications and responses. In all trials the placebo group improved
      over baseline (pooled improvement 0.39 DI units, 95% CI 0.26-0.54). There was
      insufficient data to examine toxicity. REVIEWER'S CONCLUSIONS: Parenteral high
      dose methotrexate and salazopyrin are the only two agents with well demonstrated
      published efficacy in psoriatic arthritis. The magnitude of the effect seen with
      azathioprine, etretinate, oral low dose methotrexate and perhaps colchicine
      suggests that they may be effective but that further multicentre clinical trials
      are required to establish their efficacy. Furthermore, the magnitude of the
      improvement observed in the placebo group strongly suggests that uncontrolled
      trials should not be used to guide management decisions in this condition.

PMID- 10908465
TI  - Training health professionals in smoking cessation.
AB  - BACKGROUND: There is good evidence that brief interventions from health
      professionals can increase rates of smoking cessation. A number of trials have
      examined whether specific skills training for health professionals leads them to
      have greater success in helping their patients who smoke. OBJECTIVES: The aim of
      this review was to assess the effectiveness of training health care professionals
      to deliver smoking cessation interventions to their patients, and to assess the
      additional effects of prompts and reminders to the health professional to
      intervene. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group
      trials register for studies relating to training. SELECTION CRITERIA: Randomised
      trials in which the intervention was training of health care professionals in
      smoking cessation. Trials were considered if they reported outcomes for patient
      smoking rates at least six months after the intervention. We reported on process
      outcomes, but we excluded trials that reported effects only on process outcomes
      and not smoking behaviour. DATA COLLECTION AND ANALYSIS: We extracted data in
      duplicate on the type of health professionals, the nature of and duration of the
      training, the outcome measures, method of randomisation, and completeness of
      follow-up. The main outcome measures were 1. Rates of abstinence from smoking
      after at least six months follow-up in patients smoking at baseline. 2. Rates of
      performance of tasks of smoking cessation by health care professionals including
      offering counselling, setting quit dates, giving follow-up appointments,
      distributing self-help materials and recommending nicotine gum. MAIN RESULTS:
      Healthcare professionals who had received training were more likely to perform
      tasks of smoking cessation than untrained controls. Of eight studies that
      compared patient smoking behaviour between trained professionals and controls,
      six found no effect of intervention. The effects of training on process outcomes
      increased if prompts and reminders were used. REVIEWER'S CONCLUSIONS: Training
      health professionals to provide smoking cessation interventions had a measurable
      effect on professional performance. There was no strong evidence that it changed
      smoking behaviour.

PMID- 10908466
TI  - Interventions for treating trichomoniasis in women.
AB  - BACKGROUND: Around 120 million women worldwide suffer from Trichomonas vaginalis
      vaginitis every year. The infection is sexually transmitted and is believed to
      facilitate HIV transmission. OBJECTIVES: To assess the effects of various
      treatment strategies for trichomoniasis in women. SEARCH STRATEGY: We searched
      the Cochrane Controlled Trials Register, MEDLINE, and EMBASE. Trials were also
      identified from reference lists of reviews, through pharmaceutical companies, and
      by informal discovery. Only published data were used in this review. Date of the
      most recent search: May, 2000. SELECTION CRITERIA: Randomised or quasi-randomised
      trials of different treatment strategies in women with trichomoniasis. Different
      antitrichomonal drugs or doses were eligible, as were comparisons of treatment
      with no treatment or placebo. DATA COLLECTION AND ANALYSIS: Trial quality was
      assessed and data extracted by two reviewers independently using standard
      criteria. MAIN RESULTS: Fifty-three trials were included. Nitroimidazole drugs
      seem to be effective in achieving parasitological cure in short term follow up.
      Partner treatment can be effective in decreasing longer term reinfection rates.
      REVIEWER'S CONCLUSIONS: Parasitological cure can be achieved by single oral dose
      of nitroimidazoles. Further research should focus on developing effective partner
      treatment strategies to prevent reinfections and reduce trichomoniasis
      prevalence.

PMID- 10908467
TI  - Beta-blocker supplementation of standard drug treatment for schizophrenia.
AB  - BACKGROUND: Many people with schizophrenia or similar severe mental disorders do
      not achieve a satisfactory treatment response with ordinary antipsychotic drug
      treatment. In these cases, various add-on medications are used, among them beta
      adrenergic receptor antagonists (beta-blockers). OBJECTIVES: To evaluate the
      clinical effects of beta-blockers as an adjunct to antipsychotic medication in
      schizophrenia or similar severe mental disorders. SEARCH STRATEGY: Publications
      in all languages were searched from the following databases: Biological Abstracts
      (1982-1999), The Cochrane Library (Issue 2, 1998), The Cochrane Schizophrenia
      Group's Register (December 1999), EMBASE (1980-1999), LILACS (1982-1996), MEDLINE
      (1966-1999) and PsycLIT (1974-1999). Reference sections of included papers were
      screened. SELECTION CRITERIA: All randomised controlled trials comparing beta
      blockers with placebo as an adjunct to conventional antipsychotic medication for
      those with schizophrenia. DATA COLLECTION AND ANALYSIS: Studies were selected and
      then data extracted, independently, by at least two reviewers. Odds ratios (OR)
      and 95% confidence intervals (CI) of homogeneous dichotomous data were calculated
      using the Peto method. A random effects model was used for heterogeneous
      dichotomous data. Weighted mean differences were calculated for continuous data.
      MAIN RESULTS: Currently the review includes five studies but data are poorly
      presented and there is no evidence of any effect of beta-blockers as an adjunct
      to conventional antipsychotic medication. REVIEWER'S CONCLUSIONS: At present beta
      blockers cannot be recommended in the treatment of schizophrenia. Any possible
      benefit of adjunctive beta-blockers is obscured by poor reporting within included
      studies. Existing data on beta-blockers as adjunctive medication to
      antipsychotics for those with schizophrenia should be collected and re-analysed
      in order to allow confident conclusions about the effect of this treatment or the
      need for further trials.

PMID- 10908468
TI  - Amphotericin B vs fluconazole for controlling fungal infections in neutropenic
      cancer patients.
AB  - BACKGROUND: Systemic fungal infection is considered to be an important cause of
      morbidity and mortality in cancer patients, particularly those with neutropenia.
      Antifungal drugs are often given prophylactically, or to patients with persistent
      fever. OBJECTIVES: To compare the effect of fluconazole and amphotericin B on
      morbidity and mortality in patients with cancer complicated by neutropenia.
      SEARCH STRATEGY: MEDLINE and Cochrane Library (March 2000). Letters, abstracts,
      and unpublished trials. The industry and authors were contacted. SELECTION
      CRITERIA: Randomised trials comparing fluconazole with amphotericin B. DATA
      COLLECTION AND ANALYSIS: Data on mortality, invasive fungal infection,
      colonisation, use of additional (escape) antifungal therapy and adverse effects
      leading to discontinuation of therapy were extracted by both authors
      independently. MAIN RESULTS: Thirteen trials (2977 patients) were included. In 3
      large 3-armed trials, which comprised 43% of the patients, results for
      amphotericin B were combined with results for nystatin in a "polyene" group.
      Because nystatin is an ineffective drug in theses circumstances, this approach
      creates a bias in favour of fluconazole. Furthermore, 79% of the patients were
      randomised to oral amphotericin B, which is poorly absorbed and poorly
      documented. It was unclear whether there was overlap among the "polyene" trials.
      We were unable to obtain any information to clarify these issues from the trial
      authors or the manufacturer of fluconazole. There was no significant difference
      in effect between fluconazole and amphotericin B. Apart from the "polyene"
      trials, more patients dropped out of the study when they received amphotericin B.
      REVIEWER'S CONCLUSIONS: Amphotericin B had been disfavoured in most of the trials
      through their design or analysis. Since intravenous amphotericin B is the only
      antifungal agent with a documented effect on mortality and is considerably
      cheaper than fluconazole, it should be preferred.

PMID- 10908469
TI  - Compression for venous leg ulcers.
AB  - OBJECTIVES: To assess the effectiveness and cost-effectiveness of compression
      bandaging and stockings in the treatment of venous leg ulcers. SEARCH STRATEGY:
      Searches of 19 databases, hand searching of journals, conference proceedings and
      bibliographies. Manufacturers of compression bandages and stockings and an
      Advisory Panel were contacted for unpublished studies. SELECTION CRITERIA: Trials
      that evaluated compression bandaging or stockings, as a treatment for venous leg
      ulcers. There was no restriction on date or language. Ulcer healing was the
      primary endpoint. DATA COLLECTION AND ANALYSIS: Details of eligible studies were
      extracted and summarised using a data extraction sheet. Data extraction was
      verified by two reviewers independently. MAIN RESULTS: Twenty two trials
      reporting 24 comparisons were identified. Compression was more effective than no
      compression (4/6 trials). When multi-layered systems were compared, elastic
      compression was more effective than non-elastic compression (5 trials). There was
      no difference in healing rates between 4-layer bandaging and other high
      compression multi-layered systems (3 trials). There was no difference in healing
      rates between elastomeric multi-layered systems (4 trials). Multi-layered high
      compression was more effective than single layer compression (4 trials).
      Compression stockings were evaluated in two trials. One found a high compression
      stocking plus a thrombo stocking to be more effective than a short stretch
      bandage. The second small trial reported no difference between the compression
      stockings and Unna's boot. There was insufficient data to draw conclusion about
      the relative cost-effectiveness of different regimens. REVIEWER'S CONCLUSIONS:
      Compression increases ulcer healing rates compared with no compression. Multi
      layered systems are more effective than single-layered systems. High compression
      is more effective than low compression but there are no clear differences in the
      effectiveness of different types of high compression.

PMID- 10908470
TI  - Interventions for treating scabies.
AB  - BACKGROUND: Scabies is a common public health problem with an estimated global
      prevalence of 300 million. Infestation can cause considerable discomfort and
      intense itching. Severe adverse effects have been reported for some drugs used to
      treat scabies. OBJECTIVES: The objective of this review is to assess the effects
      and toxicity of topical and systemic drug treatment for scabies. SEARCH STRATEGY:
      We searched the Cochrane Infectious Diseases Group trials register, the Cochrane
      Controlled Trials Register, MEDLINE, EMBASE, military records, traditional
      medicine databases. We also contacted international specialist centres and drug
      manufacturers. SELECTION CRITERIA: Randomised controlled trials of any drug
      treatment for scabies. Tolerability and toxicity were sought in any study of
      humans taking any drug treatments for scabies. DATA COLLECTION AND ANALYSIS: Two
      reviewers assessed trial quality and extracted data. MAIN RESULTS: Thirteen
      trials were included (nine compared drug treatments, two compared treatment
      regimens, one compared the drug vehicle, and one was a community intervention).
      In one small trial, ivermectin was associated with a significant higher clinical
      cure rate at seven days when compared with placebo. Permethrin appeared to be
      more effective than crotamiton for clinical and parasitic cure rates. Permethrin
      appeared to be better than lindane for clinical cure rates in two small trials,
      but had no advantage in the largest trial (test for heterogeneity P < 0.001).
      Permethrin also appeared more effective in reducing itch persistence than
      lindane. There appeared to be no difference in clinical cure rates between
      crotamiton and lindane or benzyl benzoate and sulphur. Two trials assessed: the
      effectiveness of oral versus topical treatment (ivermectin versus benzyl benzoate
      and ivermectin ); single trial assessed treatment vehicle (pork fat versus cold
      cream); and mass community treatment (ivermectin), but all were too small to
      demonstrate an effect. No randomised trials of malathion were identified. Serious
      adverse drug reactions (including death and convulsions), most notably to
      lindane, permethrin and ivermectin, have been reported elsewhere. REVIEWER'S
      CONCLUSIONS: The evidence that permethrin is more effective than lindane is
      inconsistent. Lindane, permethrin, and ivermectin appear to be associated with
      rare but serious drug reactions although this is not derived from trial data.
      More research is needed on the safety and effectiveness of ivermectin and
      malathion compared to permethrin, on community management, and on different
      regimens and vehicles for topical treatment.

PMID- 10908471
TI  - Expanding the roles of outpatient pharmacists: effects on health services
      utilisation, costs, and patient outcomes.
AB  - BACKGROUND: In recent years pharmacists' roles have expanded from packaging and
      dispensing medications to working with other health care professionals and the
      public. OBJECTIVES: To examine the effect of expanding outpatient pharmacists'
      roles on health services utilisation, costs, and patient outcomes. SEARCH
      STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care
      Group specialised register, MEDLINE, EMBASE, Pharmline, and International
      Pharmaceutical Abstracts (January 1966 to March 1999), the published abstracts of
      three meetings, hand searched five journals and two bibliographies, and reference
      lists of articles. SELECTION CRITERIA: Randomised trials, controlled clinical
      trials, controlled before and after studies and interrupted time series analyses
      comparing 1. Pharmacist services targeted at patients versus services delivered
      by other health professionals; 2. Pharmacist services targeted at patients versus
      the delivery of no comparable service; 3. Pharmacist services targeted at health
      professionals versus services delivered by other health professionals; 4.
      Pharmacist services targeted at health professionals versus the delivery of no
      comparable service. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      extracted data and assessed study quality. MAIN RESULTS: Twenty-five studies were
      included involving more than 40 pharmacists and 16,000 patients. For comparison 1
      (one study), scheduled service utilisation was slightly increased, whereas
      hospital admissions and emergency room admissions were decreased. For comparison
      2, pharmacist services decreased the use of non-scheduled health services, the
      number of specialty physician visits or the number and costs of drugs, compared
      to control patients (six studies). Improvements in the targeted patient condition
      were reported in 10 of 13 studies that measured patient outcomes but patients'
      quality of life did not seem to change. For comparison 3 (one study), the
      intervention delivered by the pharmacist was less successful than that delivered
      by physician counsellors in decreasing inappropriate prescribing. For comparison
      4, all studies demonstrated that pharmacist interventions produced the intended
      effects on physicians prescribing practices. The one study measuring patient
      outcomes was unable to show a difference in patients' quality of life. REVIEWER'S
      CONCLUSIONS: Only two studies compared pharmacist services with other health
      professional services. Both had some bias and did not allow us to draw
      conclusions about comparisons 1 and 3. The other studies supported the expanded
      roles of pharmacists in patient counselling and physician education. However,
      doubts about the generalisability of the studies, the poorly defined
      interventions, and the lack of cost assessments and patient outcome data,
      indicate that more rigorous research is needed to document the effects of
      outpatient pharmacist interventions.

PMID- 10908472
TI  - Extramedullary fixation implants for extracapsular hip fractures.
AB  - BACKGROUND: Extramedullary fixation of hip fractures refers to the application of
      a plate and screws to the lateral side of the proximal femur. OBJECTIVES: To
      compare different types of extramedullary fixation implants for the surgical
      treatment of extracapsular hip fracture in adults. SEARCH STRATEGY: We searched
      the Cochrane Musculoskeletal Injuries Group trials register and reference lists
      of relevant articles. Date of the most recent search: October 1999. SELECTION
      CRITERIA: All randomised or quasi-randomised trials comparing extramedullary
      implants used in the fixation of extracapsular hip fracture in adults. DATA
      COLLECTION AND ANALYSIS: All three reviewers independently assessed trial
      quality, using a ten item scale, and extracted data. Additional information was
      sought from all trialists. Wherever appropriate and possible, results of outcome
      measures were pooled by comparison. MAIN RESULTS: All seven included trials had
      methodological flaws which may have resulted in serious bias. Three trials
      involving 355 patients compared a fixed nail plate (Jewett or McLaughlin) with
      the sliding hip screw (SHS). The limited data presented indicated an increased
      risk of fixation failure outcomes for fixed nail plates. One trial involving 233
      patients compared the RAB plate (a fixed angle blade plate with an oblique
      connecting strut) with the SHS. In this trial both implants had a high incidence
      of fixation failure. There was a tendency to a lower incidence of cut-out, re
      operation, fixation failure, leg shortening, varus deformity and mortality for
      the RAB plate. None of the differences in these outcomes were statistically
      significant. One trial involving 100 patients compared the Pugh nail and the SHS.
      There was no significant difference between implants for the outcome measures
      reported. One trial involving 178 patients with 182 fractures, compared the
      Medoff plate with the SHS. A significantly higher mean operative blood loss and
      longer mean operative time were reported for the Medoff plate. There was however
      a tendency to a lower risk of fixation failure for unstable trochanteric
      fractures fixed with the Medoff plate. One trial involving 107 patients with
      subtrochanteric fractures compared the Medoff plate with three different screw
      plate systems. There was a tendency to a lower fixation failure rate for the
      Medoff plate, but no evidence for differences in longer term outcomes. REVIEWER'S
      CONCLUSIONS: The fixed nail plate has higher risks of implant breakage and
      fixation failure than the SHS. Though insufficient evidence on other outcomes is
      available from randomised trials, the increased fixation failure rate is a major
      consideration and thus the SHS appears preferable. Insufficient information is
      available to draw firm conclusions of the clinical significance of differences
      between the SHS and either the RAB plate, the Pugh nail or the Medoff plate.

PMID- 10908473
TI  - Interventions for treating plantar heel pain.
AB  - BACKGROUND: Ten percent of people may experience pain under the heel (plantar
      heel pain) at some time. Injections, insoles, heel pads, strapping and surgery
      have been common forms of treatment offered. The absolute and relative
      effectiveness of these interventions are poorly understood. OBJECTIVES: The
      objective of this review was to identify and evaluate the evidence for
      effectiveness of treatment in treating plantar heel pain. SEARCH STRATEGY:
      MEDLINE (from 1966 to December 1997), EMBASE and the Cochrane Library were
      searched. Three podiatry journals (The Foot, The Chiropodist (later The Journal
      of British Podiatric Medicine), and The British Journal of Podiatric Medicine)
      were handsearched. We contacted known investigators in the field to identify
      unpublished data or research in progress. Non English language reports were
      excluded from the review. SELECTION CRITERIA: Randomised and quasi randomised
      trials of interventions for plantar heel pain in adults. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently evaluated studies for inclusion, extracted
      data and assessed study quality. Additional information was obtained by direct
      contact with investigators. No poolable data were identified. Where measures of
      variance were available we have calculated the weighted mean differences based on
      visual analogue scale (VAS) scores. MAIN RESULTS: Eleven randomised trials
      involving 465 participants were included. Study quality was generally poor, and
      pooling of data was not possible. All studies measured a reduction in heel pain
      as the primary outcome. Seven trials evaluated interventions against
      placebo/dummy or no treatment. There was limited evidence for the effectiveness
      of topical corticosteroid, administered by iontophoresis in reducing pain. There
      was no evidence for the effectiveness of injected corticosteroid. There was
      limited evidence for the effectiveness of low energy extracorporeal shock wave
      therapy in reducing night pain, resting pain and pressure pain in the short term
      (12 weeks). In individuals with chronic pain (longer than six months), there was
      limited evidence for the effectiveness of dorsiflexion night splints in reducing
      pain. There was no evidence to support the effectiveness of therapeutic
      ultrasound, low-intensity laser therapy, exposure to an electron generating
      device or insoles with magnetic foil. No randomised trials evaluating orthotic
      devices, surgery, or radiotherapy against a control population were identified.
      There was limited evidence for the superiority of corticosteroid injections over
      orthotic devices. REVIEWER'S CONCLUSIONS: Although there is limited evidence for
      the effectiveness of local corticosteroid therapy, the effectiveness of other
      frequently employed treatments in altering the clinical course of plantar heel
      pain has not been established in comparative studies. Well designed and conducted
      randomised studies are required.

PMID- 10908474
TI  - Ovarian ablation for early breast cancer.
AB  - BACKGROUND: Among women with early breast cancer, the effects of ovarian ablation
      on recurrence and death have been assessed by several randomised trials that now
      have long follow-up. OBJECTIVES: In this report, the Early Breast Cancer
      Trialists' Collaborative Group present their third 5-yearly systematic overview
      (meta-analysis), now with 15 years' follow-up. SEARCH STRATEGY: Trial
      identification procedures for the EBCTCG overviews have been described elsewhere.
      See under "EBCTCG" in the Breast Cancer Collaborative Review Group module.
      SELECTION CRITERIA: All properly randomised trials that began recruiting before
      1990 which compared the ablation or suppression of ovarian function, sometimes
      with the addition of prednisone, versus no such adjuvant treatment for women with
      operable breast cancer. In practice, all the trials that can be reviewed here
      began before 1980, and all involved surgical or therapeutic ablation. DATA
      COLLECTION AND ANALYSIS: In 1995, information was sought on each patient in any
      randomised trial of ovarian ablation or suppression versus control that began
      before 1990. Data were obtained for 12 of the 13 studies that assessed ovarian
      ablation by irradiation or surgery, all of which began before 1980, but not for
      the four studies that assessed ovarian suppression by drugs, all of which began
      after 1985. Menopausal status was not consistently defined across trials;
      therefore, the main analyses are limited to women aged under 50 (rather than
      "premenopausal") when randomised. Oestrogen receptors were measured only in the
      trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy
      alone. MAIN RESULTS: Among 2102 women aged under 50 when randomised, most of whom
      would have been premenopausal at diagnosis, 1130 deaths and an additional 153
      recurrences were reported. 15-year survival was highly significantly improved
      among those allocated ovarian ablation (52.4 vs 46.1%, 6.3 [SD 2.3] fewer deaths
      per 100 women, logrank 2p=0.001), as was recurrence-free survival (45.0 vs 39.0%,
      2p=0.0007). The numbers of events were too small for any subgroup analyses to be
      reliable. The benefit was, however, significant both for those with ("node
      positive") and for those without ("node negative") axillary spread when
      diagnosed. In the trials of ablation plus cytotoxic chemotherapy versus the same
      chemotherapy alone, the benefit appeared smaller (even for women with oestrogen
      receptors detected on the primary tumour) than in the trials in the absence of
      chemotherapy (where the observed survival improvements were about six per 100
      node-negative women and 12 per 100 node-positive women). Among 1354 women aged 50
      or over when randomised, most of whom would have been perimenopausal or
      postmenopausal, there was only a non-significant improvement in survival and
      recurrence-free survival. REVIEWER'S CONCLUSIONS: In women aged under 50 with
      early breast cancer, ablation of functioning ovaries significantly improves long
      term survival, at least in the absence of chemotherapy. Further randomised
      evidence is needed on the additional effects of ovarian ablation in the presence
      of other adjuvant treatments, and to assess the relevance of hormone-receptor
      measurements.

PMID- 10908475
TI  - Target payments in primary care: effects on professional practice and health care
      outcomes.
AB  - BACKGROUND: The method by which physicians are paid may affect their professional
      practice. Although payment systems may be used to achieve policy objectives (e.g.
      improving quality of care, cost containment and recruitment to under-served
      areas), little is known about the effects of different payment systems in
      achieving these objectives. Target payments are a payment system which remunerate
      professionals only if they provide a minimum level of care. OBJECTIVES: To
      evaluate the impact of target payments on the professional practice of primary
      care physicians (PCPs) and health care outcomes. SEARCH STRATEGY: We searched the
      Cochrane Effective Practice and Organisation of Care Group specialised register;
      the Cochrane Controlled Trials Register; MEDLINE (1966 to October 1997); BIDS
      EMBASE (1980 to October 1997); BIDS ISI (1981 to October 1997); EconLit (1969 to
      October 1997); HealthStar (1975 to October 1997) Helmis (1984 to October 1997);
      health economics discussion paper series of the Universities of York, Aberdeen,
      Sheffield, Bristol, Brunel, and McMaster; Swedish Institute of Health Economics;
      RAND corporation; and reference lists of articles. SELECTION CRITERIA: Randomised
      trials, controlled before and after studies and interrupted time series analyses
      of interventions comparing the impact of target payments to primary care
      professionals with alternative methods of payment, on patient outcomes, health
      services utilisation, health care costs, equity of care, and PCP satisfaction
      with working environment. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted data and assessed study quality. MAIN RESULTS: Two
      studies were included involving 149 practices. The use of target payments in the
      remuneration of PCPs was associated with improvements in immunisation rates, but
      the increase was statistically significant in only one of the two studies.
      REVIEWER'S CONCLUSIONS: The evidence from the studies identified in this review
      is not of sufficient quality or power to obtain a clear answer to the question as
      to whether target payment remuneration provides a method of improving primary
      health care. Additional efforts should be directed in evaluating changes in
      physicians' remuneration systems. Although it would not be difficult to design a
      randomised controlled trial to evaluate the impact of such payment systems, it
      would be difficult politically to conduct such trials.

PMID- 10908476
TI  - On-site mental health workers in primary care: effects on professional practice.
AB  - BACKGROUND: Mental health problems are common in primary care and mental health
      workers (MHWs) are increasingly working in this setting. In addition to treating
      patients, the introduction of on-site MHWs may lead to changes in the clinical
      behaviour of primary care providers (PCPs). OBJECTIVES: To assess the effects of
      on-site MHWs in primary care on the clinical behaviour of primary care providers
      (PCPs). SEARCH STRATEGY: We searched the Cochrane Effective Practice and
      Organisation of Care Group specialised register (18-22 June 1998), the Cochrane
      Controlled Trials Register (18-22 June 1998), MEDLINE (1966 to 1998), EMBASE
      (1980 to 1998), PsychInfo (1984 to 1998), CounselLit (18-22 June 1998), NPCRDC
      skill-mix in primary care bibliography, and reference lists of articles.
      SELECTION CRITERIA: Randomised trials, controlled before and after studies and
      interrupted time series analyses of MHWs either replacing PCPs as providers of
      mental health care ('replacement' models) or providing collaborative care/support
      to PCPs in managing patients' mental health problems ('consultation-liaison'
      models). The participants were primary care providers. The outcomes included
      objective PCP behaviours such as diagnosis, prescribing and referral. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed
      study quality. MAIN RESULTS: Thirty-eight studies were included involving more
      than 460 PCPs and more than 3880 patients. There was some evidence that
      'replacement' model MHWs achieved significant short-term reductions in PCP
      psychotropic prescribing and mental health referral, but the effects were not
      reliable. Consultation rates were also reduced, but with even less evidence of a
      consistent effect. There were no indirect effects in prescribing behaviour on the
      wider population and no consistent pattern to the impact on referrals. 'Indirect'
      effects on PCP consultation rates were not assessed. There was some evidence that
      'consultation-liaison' model MHWs had a direct effect on PCP prescribing
      behaviour when used as part of complex, multifaceted interventions. Few studies
      examined the 'indirect' effects of such interventions, and those that did failed
      to provide evidence that 'direct' effects were generalisable to the wider
      population or endured once the 'consultation-liaison' intervention was removed.
      REVIEWER'S CONCLUSIONS: This review does not support the hypothesis that adding
      MHWs to primary care provider organisations in 'replacement' models causes a
      significant or enduring change in PCP behaviour. 'Consultation-liaison'
      interventions may cause changes in psychotropic prescribing, but these seem short
      term and limited to patients under the direct care of the MHW. Longer-term
      studies are needed to assess the degree to which demonstrated effects endure over
      time.

PMID- 10908477
TI  - Day care for pre-school children.
AB  - BACKGROUND: The debate about how, where and by whom young children should be
      looked after is one which has occupied much social policy and media attention in
      recent years. Mothers undertake most of the care of young children.
      Internationally, out-of-home day-care provision ranges widely. These different
      levels of provision are not simply a response to different levels of demand for
      day-care, but reflect cultural and economic interests concerning the welfare of
      children, the need to promote mothers' participation in paid work, and the
      importance of socialising children into society's values. At a time when a
      decline in family values is held responsible for a range of social problems, the
      day-care debate has a special prominence. OBJECTIVES: To quantify the effects of
      out-of-home day-care for preschool children on educational, health and welfare
      outcomes for children and their families. SEARCH STRATEGY: Randomised controlled
      trials of day-care for pre-school children were identified using electronic
      databases, hand searches of relevant literature, and contact with authors.
      SELECTION CRITERIA: Studies were included in the review if the intervention
      involved the provision of non-parental day care for children under 5 years of
      age, and the evaluation design was that of a randomised or quasi-randomised
      controlled trial. DATA COLLECTION AND ANALYSIS: A total of eight trials were
      identified after examining 920 abstracts and 19 books. The trials were assessed
      for methodological quality. MAIN RESULTS: Day-care increases children's IQ, and
      has beneficial effects on behavioural development and school achievement. Long
      term follow up demonstrates increased employment, lower teenage pregnancy rates,
      higher socio-economic status and decreased criminal behaviour. There are positive
      effects on mothers' education, employment and interaction with children. Effects
      on fathers have not been examined. Few studies look at a range of outcomes
      spanning the health, education and welfare domains. Most of the trials combined
      non-parental day-care with some element of parent training or education (mostly
      targeted at mothers); they did not disentangle the possible effects of these two
      interventions. The trials had other significant methodological weaknesses,
      pointing to the importance of improving on study design in this field. All the
      trials were carried out in the USA. REVIEWER'S CONCLUSIONS: Day care has
      beneficial effect on children's development, school success and adult life
      patterns. To date, all randomised trials have been conducted among disadvantaged
      populations in the USA. The extent to which the results are generaliseable to
      other cultures and socioeconomic groups has yet to be evaluated.

PMID- 10908478
TI  - Quetiapine for schizophrenia.
AB  - BACKGROUND: Quetiapine is a novel atypical antipsychotic with, theoretically, a
      low propensity for movement disorder adverse effects. It is used for treatment of
      schizophrenia and other psychoses. OBJECTIVES: To determine the effects of
      quetiapine for schizophrenia in comparison to placebo, classical and other
      atypical antipsychotics. SEARCH STRATEGY: Electronic searches of Biological
      Abstracts (1982-2000), CINAHL (1982-2000), the Cochrane Library (2000, Issue 1),
      the Cochrane Schizophrenia Group's Register of trials (Feb 2000), EMBASE (1980
      2000), MEDLINE (1966-2000), PsycLIT (1974-2000), SIGLE on CD (1980-1997),
      SocioFile (1974-1997) and many conference proceedings and hand searches of
      specific journals were undertaken. AstraZeneca Pharmaceuticals was contacted for
      information regarding unpublished trials. SELECTION CRITERIA: All controlled
      trials where adults with schizophrenia or similar illnesses were randomised to
      quetiapine, placebo or other neuroleptic drugs and where clinically relevant
      outcomes were reported. DATA COLLECTION AND ANALYSIS: Citations and, where
      possible, abstracts were independently inspected by reviewers, papers ordered, re
      inspected and quality assessed. Data were also independently extracted. The
      Relative Risk (RR) with 95% confidence intervals (CI) was used. A fixed effect
      model was used for a data set with non-significant heterogeneity. A random effect
      model was used for data sets with significant heterogeneity. In addition, as a
      measure of efficacy, the number needed to treat (NNT) was also calculated. For a
      continuous outcome, a weighted mean difference (WMD) between groups was
      estimated. A fixed effect model was used for a data set with non-significant
      heterogeneity. A random effect model was used for a data set with significant
      heterogeneity. MAIN RESULTS: Forty-two papers and reports (11 randomised
      controlled trials) were included in the review while 155 were excluded. Apart
      from the outcome, 'leaving the study early', all other results may be prone to
      bias and should be viewed with caution since dropout rates are high (36-64%) in
      these trials of short duration. In comparison to placebo, there are data
      suggesting that people allocated to quetiapine are less likely to leave the study
      early (RR 0.84, CI 0.73 to 0.97) particularly when the reason given was due to
      treatment failure. Dichotomous data relating to psychotic symptoms show a
      significant improvement in the quetiapine group (RR 0.79, CI 0.67 to 0.92, NNT
      8). No significant difference could be found in respect of needing medication for
      extrapyramidal side effects, as well as for incidences of parkinsonism, akathisia
      and dystonia. In comparison to classical antipsychotics, the proportion of people
      leaving the studies early is significantly, but marginally, less for the
      quetiapine group (RR 0.87, CI 0.76 to 0.99). No significant difference between
      the two groups shows with regard to global state and mental state. Quetiapine may
      produce lower incidences of using medication for extrapyramidal side effects such
      as parkinsonism, akathisia and dystonia. Most data are very short term. In
      comparison to the low dose quetiapine group, the number of people leaving the
      three studies is significantly smaller in the high dose group (RR 0. 84, CI 0.75
      to 0.94). The improvement on mental state was significantly higher in the high
      dose group. Incidences of akathisia, dystonia, parkinsonism and needing
      medication for extrapyramidal side effects were the same for both doses of
      quetiapine. REVIEWER'S CONCLUSIONS: High dropout rates in short quetiapine
      studies are a major problem, and makes interpreting any results problematic.
      Before quetiapine's use can be recommended, more large, well conducted trials
      that provide short, medium and long term outcomes relevant to carers and
      clinicians are necessary.

PMID- 10908479
TI  - Cognitive rehabilitation for people with schizophrenia and related conditions.
AB  - BACKGROUND: Researchers have consistently found that people with schizophrenia
      score more poorly than others on a wide array of cognitive tasks and that these
      deficits persist even when the illness is in remission. The perceived impact of
      cognitive impairment on day-to-day functioning has led to the development of
      cognitive rehabilitation techniques intended to remedy these impairments, and
      thus improve the functioning of people with schizophrenia. OBJECTIVES: To
      determine whether the use of cognitive rehabilitation techniques is associated
      with improvement in people with schizophrenia and related conditions. SEARCH
      STRATEGY: Electronic searches of Biological Abstracts (1982-1997), the Cochrane
      Schizophrenia Group's Register of trials (2000), EMBASE (1980-1997), LILACS (1982
      1997), MEDLINE (1966-1997), PsycLIT (1974-1997) and SCISEARCH (1997) were
      undertaken. References of all identified studies were handsearched and the first
      author of each included trial was contacted. SELECTION CRITERIA: The reviewers
      included randomised trials investigating the impact of cognitive rehabilitation
      on people with schizophrenia, or related conditions, compared to a placebo
      intervention, another intervention or standard treatment. This version of the
      review does not include comparisons of different types of cognitive
      rehabilitation. DATA COLLECTION AND ANALYSIS: Relevant studies were identified
      and data extracted reliably by two reviewers working independently. In studies
      which did not specify the reasons for participants dropping out, we assumed that
      those who had dropped out had experienced no change in the outcome measures.
      Where possible, Peto odds ratios (OR) and mean differences (MD) were calculated
      with their 95% confidence intervals (CI). MAIN RESULTS: Three small studies met
      the inclusion criteria. Two compared cognitive rehabilitation to a placebo
      intervention (total n=84), and the other to occupational therapy (n=33). Although
      cognitive rehabilitation was as acceptable as placebo and occupational therapy,
      with low attrition in both groups, no effects were demonstrated on measures of
      mental state, social behaviour, or cognitive functioning. An effect, in favour of
      cognitive rehabilitation, on a measure of self-esteem (Rosenberg Self-Esteem
      Scale, MD 6.3 CI 1.07-11.53 ) is worthy of replication in any future trials.
      REVIEWER'S CONCLUSIONS: Data are inconclusive and provide no evidence for or
      against cognitive rehabilitation as a treatment for schizophrenia.

PMID- 10908480
TI  - Amphotericin B lipid soluble formulations vs amphotericin B in cancer patients
      with neutropenia.
AB  - BACKGROUND: Patients with cancer who are treated with chemotherapy or receive a
      bone marrow transplant have an increased risk of acquiring fungal infections.
      Such infections can be life-threatening. Antifungal drugs are therefore often
      given prophylactically to such patients, or when they have a fever. OBJECTIVES:
      To compare the effect and adverse effects of AmBisome and other lipid soluble
      formulations of amphotericin B with conventional amphotericin B in cancer
      patients with neutropenia. SEARCH STRATEGY: MEDLINE and Cochrane Library.
      Unpublished trials from conference proceedings and contact to industry. SELECTION
      CRITERIA: Randomised trials comparing lipid soluble formulations of amphotericin
      B with conventional amphotericin B. DATA COLLECTION AND ANALYSIS: Data on
      mortality, invasive fungal infection, nephrotoxicity, serum creatinine and
      dropouts were extracted by both authors independently. MAIN RESULTS: AmBisome vs
      conventional amphotericin B (3 trials, 1149 patients): AmBisome tended to be more
      effective than conventional amphotericin B for invasive fungal infection
      (relative risk 0.63, 95% confidence interval 0.39 to 1.01, P=0.053) whereas there
      was no significant difference in mortality (relative risk 0.74, 95% CI 0.52 to
      1.07). AmBisome decreased significantly the incidence of nephrotoxicity, defined
      as a 100% increase in serum creatinine (relative risk 0.51, 95% CI 0.40 to 0.64).
      Fewer patients dropped out on AmBisome but the difference was not significant
      (relative risk 0.78, 95% CI 0.56 to 1. 08). Amphotericin B in Intralipid vs
      conventional amphotericin B (4 trials, 145 patients): There were no significant
      differences in clinical effect whereas the patients treated with the lipid
      soluble formulation experienced significantly less nephrotoxicity (relative risk
      0.34, 95% CI 0.15 to 0.75) and smaller increases in serum creatinine (weighted
      mean difference 32 micromol/l, 95% CI 21 to 43 micromol/l). Amphotericin B
      colloidal dispersion (ABCD) vs conventional amphotericin B (1 trial, 213
      patients): There was lower nephrotoxicity with ABCD (relative risk 0.38, 95% CI
      0.25 to 0.59). REVIEWER'S CONCLUSIONS: AmBisome is a better drug than
      conventional amphotericin B but its high cost prohibits routine use in most
      settings. Furthermore, the advantages of AmBisome may be smaller than indicated
      in our review if conventional amphotericin B is administered under optimal
      circumstances. It is not clear whether other lipid formulations of amphotericin B
      could offer a worthwhile advantage compared to conventional amphotericin B.

PMID- 10908481
TI  - Nutritional supplementation in stable chronic obstructive pulmonary disease.
AB  - BACKGROUND: Low body weight in patients with chronic obstructive pulmonary
      disease (COPD) is associated with an impaired pulmonary status, reduced
      diaphragmatic mass, lower exercise capacity and higher mortality rate when
      compared to adequately nourished individuals with this disease. Nutritional
      support may therefore be a useful part of their comprehensive care. OBJECTIVES:
      To conduct a systematic review of randomized controlled trials (RCTs) to clarify
      whether nutritional supplementation (caloric supplementation for at least 2
      weeks) improved anthropometric measures, pulmonary function, respiratory muscle
      strength and functional exercise capacity in patients with stable COPD. SEARCH
      STRATEGY: Randomized controlled trials (RCTs) were identified from the Cochrane
      Airways Group register of RCTs, a hand-search of abstracts presented at
      international meetings and consultation with experts. SELECTION CRITERIA: Two
      reviewers independently selected trials for inclusion, assessed quality and
      extracted the data. DATA COLLECTION AND ANALYSIS: Within each trial and for each
      outcome, we calculated an effect size. The effect sizes were then pooled by a
      random-effects model. Homogeneity among the effect sizes was also tested. MAIN
      RESULTS: From 272 references, nine RCTs were ultimately included. Six papers were
      considered as high quality and only two studies were double-blinded. For each of
      the outcomes studied, the effect of nutritional support was small: the 95%
      confidence intervals around the pooled effect sizes all included zero. The effect
      of nutritional support was homogeneous across studies. REVIEWER'S CONCLUSIONS:
      Nutritional support had no significant effect on anthropometric measures, lung
      function or exercise capacity in patients with stable COPD.

PMID- 10908482
TI  - Collection devices for obtaining cervical cytology samples.
AB  - BACKGROUND: Few randomised controlled trials have sufficient power to show clear
      advantages of different designs of cervical smear collection devices. We studies
      whether the design of the cervical smear collection device affects rates of
      inadequate smears and detection of disease and whether the presence of
      endocervical cells in the smear affects detection of disease. OBJECTIVES: The
      false-negative rate of cervical smears varies between 1.5% and 55%. This
      variation may be partly due to differences in sampling device and technique. The
      objective of this review was to assess different cervical sampling devices for
      collecting endocervical cells, which are thought to be a surrogate for detection
      of abnormal cells and adequate smear rates. SEARCH STRATEGY: We searched the
      Cochrane Gynaecological Cancer Group trials register and MEDLINE up to July 1997.
      We also handsearched 16 journals. SELECTION CRITERIA: Randomised and quasi
      randomised trials and non-randomised comparative studies comparing cervical smear
      collection devices in women attending for primary screening, colposcopy following
      an abnormal smear or colposcopy after treatment. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently abstracted data. Study quality was assessed. MAIN
      RESULTS: Thirty-four trials and six observational comparative studies were
      included. The Ayre spatula was shown to be less effective compared with extended
      tip spatulas for collecting endocervical cells in eight trials (odds ratio 2.25,
      95% confidence interval 2.06 to 2.44). Use of a spatula with the cytobrush was
      more effective than spatula alone at collecting endocervical cells (odds ratio
      3.33, 95% 3.05 to 3.63) and the same effect was present for adequate smear rates
      (odds ratio 1.51 95% 1.19-1.92). Extended tip spatulas were also superior for the
      detection of dyskaryosis in seven trials (odds ratio 1.21, 95% confidence
      interval 1.10 to 1.33). Based on data from two trials and three observational
      studies, smears that contained endocervical cells were more likely to detect
      dyskaryosis, particularly in severe disease. The proportion of smears with
      endocervical cells present increased with increasing severity of the disease.
      REVIEWER'S CONCLUSIONS: Extended tip spatulas of various designs appear to be
      better for collecting endocervical cells than the commonly used Ayre spatula. The
      most effective combination appears to be the cytobrush with an extended tip
      spatula. The rate of detection of endocervical cells appears to be a valid and
      convenient surrogate for the ability to detect dyskaryosis and for adequate smear
      rates. The ability of the extended tip spatula with the cytobrush compared with
      the extended tip spatula alone to detect disease, needs to be evaluated in a
      trial.

PMID- 10908483
TI  - Calcium supplementation during pregnancy for preventing hypertensive disorders
      and related problems.
AB  - BACKGROUND: Calcium supplementation may prevent high blood pressure through a
      number of mechanisms and may help to prevent preterm labour. OBJECTIVES: The
      objective of this review was to assess the effects of calcium supplementation
      during pregnancy on hypertensive disorders of pregnancy and related maternal and
      child adverse outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register and the Cochrane Controlled Trials Register and
      we contacted study authors. Date of last search: February 2000. SELECTION
      CRITERIA: Randomised trials comparing at least one gram daily of calcium during
      pregnancy with placebo. DATA COLLECTION AND ANALYSIS: Eligibility and trial
      quality were assessed. Data extraction was carried out and double entered. MAIN
      RESULTS: Ten studies were included, all of good quality. There was a modest
      reduction in high blood pressure with calcium supplementation (relative risk
      0.81, 95% confidence interval 0.74 to 0.89). The effect was greatest for women at
      high risk of hypertension (relative risk 0.35, 95% confidence interval 0.21 to
      0.57) and those with low baseline dietary calcium (relative risk 0.49, 95%
      confidence interval 0.38 to 0.62). There was also a modest reduction in the risk
      of pre-eclampsia with calcium supplementation (relative risk 0. 70, 95%
      confidence interval 0.58 to 0.83). The effect was greatest for women at high risk
      of hypertension (relative risk 0.22, 95% confidence interval 0.11 to 0.43) and
      those with low baseline calcium intake (relative risk 0.32, 95% confidence
      interval 0.21 to 0.49). There was no overall effect on the risk of preterm
      delivery, although there was a reduction in risk amongst women at high risk of
      hypertension (relative risk 0.43, 95% confidence interval 0.24 to 0. 79). There
      was no evidence of any effect of calcium supplementation on stillbirth or death
      before discharge from hospital. There were fewer babies with birthweight, <2500g
      (RR 0.83, 95% CI 0.71-0.98). In one study, childhood systolic blood pressure
      >95th percentile was reduced (RR0.59, 95% CI 0.39-0.91). REVIEWER'S CONCLUSIONS:
      Calcium supplementation appears to be beneficial for women at high risk of
      gestational hypertension and in communities with low dietary calcium intake.
      Optimum dosage requires further investigation.

PMID- 10908484
TI  - Antibiotics for persistent nasal discharge (rhinosinusitis) in children.
AB  - BACKGROUND: Nasal discharge (rhinosinusitis) is the result of inflammation of the
      mucosa of the upper respiratory tract, and is usually due to either infection or
      allergy. OBJECTIVES: To determine the effectiveness of antibiotics versus placebo
      or standard therapy in treating children with persistent nasal discharge (>10
      days). SEARCH STRATEGY: The Cochrane Controlled Trials Register, MEDLINE, EMBASE,
      and bibliographies of relevant articles were searched. Authors and pharmaceutical
      companies were contacted. Date of most recent searches: March 2000. SELECTION
      CRITERIA: All randomized controlled trials that compared antibiotics versus
      placebo or standard therapy (decongestants or nasal saline drops). Trials which
      included the use of other medications were included if all participants were
      allowed equal access to such medications or if the additional or alternative
      therapies were regarded as ineffective. Trials that only combined or compared
      antibiotics with surgery, or sinus puncture and lavage, were not included in the
      review. DATA COLLECTION AND ANALYSIS: Data were extracted by a single reviewer
      for the following outcomes: clinical failure, failure to improve, clinical
      improvement, time to resolution, complications, side-effects and bacteriologic
      failure. For the dichotomous outcome variables of each individual study,
      proportional and absolute risk reductions were calculated using a modified
      intention-to-treat analysis. The summary weighted risk ratio and 95% confidence
      interval (fixed effects model) were calculated using the inverse of the variance
      of each study result for weighting (Cochrane statistical package, REVMAN version
      4.3). MAIN RESULTS: A total of five studies involving 401 children compared
      antibiotics with placebo or standard therapy. Only one of the seven outcomes
      (clinical failure) was reported in all studies. Around 45% of children did not
      have a clinical success documented when reviewed 2-6 weeks after randomization.
      The control event rate varied from to 47-71% (mean 56%). The risk ratio estimated
      using a fixed effects model was 0.72 (95% CI 0.59, 0.89). The estimated effect
      size was consistent in four of the five studies. REVIEWER'S CONCLUSIONS: For
      children with persistent nasal discharge or older children with radiographically
      confirmed sinusitis, the available evidence suggests that antibiotics given for
      10 days will reduce the probability of persistence in the short to medium-term.
      The benefits appear to be modest and around six children must be treated in order
      to achieve one additional cure. No long term benefits have been documented. These
      conclusions are based on a small number of small randomized controlled trials and
      additional larger well-designed studies are indicated.

PMID- 10908485
TI  - Azoles for allergic bronchopulmonary aspergillosis.
AB  - BACKGROUND: Allergic Broncho-pulmonary Aspergillosis (ABPA) is hypersensitivity
      to the fungus Aspergillus Fumigatus that complicates patients with asthma and
      cystic fibrosis. The condition usually results in an increase in symptoms, a
      greater reliance on corticosteroids to control the disease process and may lead
      to a progressive decline in lung function. The mainstay of treatment for ABPA
      remains oral corticosteroids, though this does not completely prevent
      exacerbations and may not prevent the decline in lung function. OBJECTIVES: The
      purpose of this review is to determine the efficacy of azoles in the treatment of
      ABPA SEARCH STRATEGY: An initial search was carried out using the Cochrane
      Airways Group Asthma RCT register. The register was searched using the following
      terms: (asthma or wheeze) and (allergic bronchopulmonary aspergillosis or
      aspergillosis or allergic pulmonary aspergillosis or allergic fungal and disease
      or allergic mycotic and disease) and (azole or triazole or itraconazole or
      ketoconazole). SELECTION CRITERIA: All controlled trials that assessed the effect
      of azole antifungal agents compared to placebo or other standard, for any
      duration or dose regimen in subjects with ABPA of any age or severity were
      reviewed. Studies in languages other than English were included. DATA COLLECTION
      AND ANALYSIS: All identified trials were independently reviewed by both reviewers
      & all data collected. Trial quality was scored by the Cochrane assessment of
      allocation concealment & the Jadad scale of methodological quality. MAIN RESULTS:
      A total of 11 trials were identified concerning the use of azoles in ABPA. Only
      two prospective controlled trials were identified. The first trial examined the
      use of Ketoconazole 400 mg daily for 12 months and demonstrated a reduction in
      immunological markers of disease activity and symptom scores, there was no
      significant improvement in lung function. The other trial examined the use of
      itraconazole for 16 weeks. This demonstrated a reduction in corticosteroid usage,
      an improvement in immunological markers, an improvement in pulmonary function and
      exercise tolerance. This study was only available as an abstract and limited
      details were available. REVIEWER'S CONCLUSIONS: There is insufficient information
      available to recommend the use of azole anti-fungal agents in the routine
      treatment of patients with ABPA.

PMID- 10908486
TI  - Music therapy for dementia symptoms.
AB  - BACKGROUND: While music/music therapy does not represent a treatment of dementia,
      its use is based on a possible beneficial effect on symptoms including social,
      emotional and cognitive skills and for decreasing behavioral problems of
      individuals with dementias. Thus, there are clear implications for patients' and
      caregivers' quality of life. However, quantification and documentation of the
      evidence of this effect is necessary. Professional music therapists are
      accountable for providing efficient, beneficial treatment. Furthermore, music
      therapists are responsible for assessing, designing and implementing music
      therapy treatments, monitoring client progress, and reformulating their practice
      according to data collected and new advancements in the field. If they wait until
      sufficient valid, empirical data on all aspects of a disability or music response
      are available before attempting to design a therapy session, they may well reach
      retirement age before even one client can be served. On the other hand,
      promulgating the efficacy of music therapy in general, or of specific music
      therapy techniques, in the absence of any substantiation other than intuition or
      tradition borders on professional recklessness. OBJECTIVES: To gather and
      evaluate the evidence for the effectiveness of music therapy for dementia
      symptoms. SEARCH STRATEGY: All available sources of references were searched in
      March 2000 for randomised controlled trials of music therapy used as an
      intervention in dementia. The search terms included 'controlled trial or study,
      music, therapy, dementia, Alzheimer's, cognitive impairment' and derivatives of
      these. SELECTION CRITERIA: The reviewers assessed the methodological quality of
      the studies available for inclusion. The criteria used are presence and adequacy
      of a control condition, independent assessment of patients' performance (ie
      standardized ratings carried out by a person other than the music therapist) and
      the number of participants (no fewer than three). DATA COLLECTION AND ANALYSIS:
      No randomised controlled trials, or trials with quantitative data suitable for
      analysis were found. MAIN RESULTS: The research into music therapy to date has
      lacked methodological design rigour. However, the research evidence available
      provides sufficient grounds on which to justify further investigations into the
      use of music therapy in dementia patients. In this context, the reviewers discuss
      some of the issues and research from the studies that were considered for
      inclusion. REVIEWER'S CONCLUSIONS: This review was not able to identify reliable
      empirical evidence on which to justify the use of music therapy as a treatment
      for dementia. However, the evidence available suggests that music therapy may be
      beneficial in treating or managing dementia symptoms, and the predominant
      conclusion of this review is the highlighting of the need for better designed
      studies of the intervention.

PMID- 10908487
TI  - Anticonvulsant drugs for acute and chronic pain.
AB  - BACKGROUND: Anticonvulsant drugs have been used in the management of pain since
      the 1960s. The clinical impression is that they are useful for chronic
      neuropathic pain, especially when the pain is lancinating or burning. OBJECTIVES:
      To evaluate the analgesic effectiveness and adverse effects of anticonvulsant
      drugs for pain management in clinical practice and to identify a clinical
      research agenda. Migraine and headache studies are excluded in this revision.
      SEARCH STRATEGY: Randomised trials of anticonvulsants in acute, chronic or cancer
      pain were identified by Medline (1966-1999), Embase (1994-1999), SIGLE (1980
      1999) and the Cochrane Controlled Trials Register (CENTRAL/CCTR) (Cochrane
      Library Issue 3, 1999). In addition, 40 medical journals were hand searched.
      Additional reports were identified from the reference list of the retrieved
      papers, and by contacting investigators. Date of most recent search: September
      1999. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of
      anticonvulsant drugs in patients, with subjective pain assessment as either the
      primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Data were extracted
      by two independent reviewers, and trials were quality scored. Numbers-needed-to
      treat (NNTs) were calculated from dichotomous data for effectiveness, adverse
      effects and drug-related study withdrawal, for individual studies and for pooled
      data. MAIN RESULTS: Twenty-three trials of six anticonvulsants were considered
      eligible (1,074 patients). The only placebo-controlled study in acute pain found
      no analgesic effect of sodium valproate. Three placebo-controlled studies of
      carbamazepine in trigeminal neuralgia had a combined NNT (95% confidence interval
      (CI)) for effectiveness of 2.5 (CI 2.0-3.4). A single placebo-controlled trial of
      gabapentin in post-herpetic neuralgia had an NNT of 3.2 (CI 2.4-5.0). For
      diabetic neuropathy NNTs for effectiveness were as follows: (one RCT for each
      drug) carbamazepine 2.3 (CI 1.6-3.8), gabapentin 3.8 (CI 2.4-8.7) and phenytoin
      2.1 (CI 1.5-3.6). Numbers-needed-to-harm (NNHs) were calculated where possible by
      combining studies for each drug entity irrespective of the condition treated. The
      results were, for minor harm, carbamazepine 3.7 (CI 2.4-7.8), gabapentin 2.5 (CI
      2.0-3.2), phenytoin 3.2 (CI 2.1-6.3). NNHs for major harm were not statistically
      significant for any drug compared with placebo. Phenytoin had no effect in
      irritable bowel syndrome, and carbamazepine little effect in post-stroke pain.
      Clonazepam was effective in one study of temporomandibular joint dysfunction.
      REVIEWER'S CONCLUSIONS: Although anticonvulsants are used widely in chronic pain
      surprisingly few trials show analgesic effectiveness. No trial compared different
      anticonvulsants. Only one studied considered cancer pain. There is no evidence
      that anticonvulsants are effective for acute pain. In chronic pain syndromes
      other than trigeminal neuralgia, anticonvulsants should be withheld until other
      interventions have been tried. While gabapentin is increasingly being used for
      neuropathic pain the evidence would suggest that it is not superior to
      carbamazepine.

PMID- 10908488
TI  - Non-steroidal anti-inflammatory drugs for preventing heterotopic bone formation
      after hip arthroplasty.
AB  - BACKGROUND: Heterotopic bone formation (HBF) in the soft tissues surrounding the
      hip joint is a frequent complication of hip surgery. Non-steroidal anti
      inflammatory drugs (NSAIDs) administered in the immediate perioperative period
      reduce the risk of HBF. However, the magnitude of the effect on HBF, and the
      effects on other associated outcomes are uncertain. OBJECTIVES: To determine the
      effects of perioperative NSAID therapy versus control on the risk of HBF and
      other outcomes in patients undergoing hip arthroplasty. SEARCH STRATEGY: Medline,
      Current Contents and Cochrane Controlled Trials Register, and reference lists of
      all relevant reports were searched. Principal investigators and the manufacturers
      of the study drugs of eligible trials were approached. The most recent search was
      conducted in July 1998. SELECTION CRITERIA: All trials which enrolled patients
      scheduled to undergo hip arthroplasty with random or quasi-random allocation to
      perioperative NSAID or control and that recorded post-operative radiographically
      determined HBF. The primary outcome was post-operative radiographic HBF.
      Secondary outcomes were pain, disability, gastro-intestinal and other bleeding
      complications, and other causes of major morbidity or mortality. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently assessed methodological quality and
      extracted data. All analyses were conducted on dichotomised outcomes. MAIN
      RESULTS: Twelve randomised and two quasi-randomised trials involving a total of
      4,377 patients were included. Overall, in 13 trials that examined the effects of
      medium to high doses of NSAIDs, there was a reduced risk of developing HBF after
      hip surgery (62% reduction, 95% confidence interval 56% to 67% reduction). In
      contrast, one large trial examining low-dose aspirin, demonstrated no effect on
      the risk of HBF (2% reduction, 95% confidence interval 15% reduction to 12%
      increase). There was strong evidence of differences in the size of the treatment
      effects observed between the trials examining medium to high doses of NSAIDs, but
      reasons were not clearly identified. There was a non-significant one third
      increased risk of gastro-intestinal side effects among patients assigned NSAIDs
      (29% increase, 95% confidence interval 5% reduction to 76% increase). Most of
      this increase was due to an increased risk of minor gastro-intestinal
      complications. Data on the late post-operative outcomes of pain, impaired
      physical function and range of joint movement were few and no formal overviews of
      the effects of NSAIDs on these outcomes were possible. REVIEWER'S CONCLUSIONS:
      Perioperative NSAIDs appear to produce between a one half and two thirds
      reduction in the risk of HBF. With routine use, such agents may be able to
      prevent 15-20 cases of HBF (3-4 severe) among every 100 total hip replacements
      performed. However, while medium to high doses of perioperative NSAIDs clearly
      produce a substantial reduction in the incidence of radiographic HBF, there
      remains some uncertainty about short-term side effects of treatment and
      substantial uncertainty about effects on long-term clinical outcomes such as
      chronic pain and impaired physical function. The net effect of routine HBF
      prophylaxis with NSAIDs requires formal assessment in a randomised trial designed
      to determine the balance of benefits and risks for all outcomes.

PMID- 10908489
TI  - Breathing exercises for asthma.
AB  - BACKGROUND: There is much anecdotal evidence in Eastern and Western literature
      describing considerable benefits for patients with asthma when treated with
      breathing interventions. The term 'breathing exercise or training' has numerous
      interpretations depending on the nature of the therapy, therapist and cultural
      background. OBJECTIVES: The objective of this review was to assess the evidence
      for the effectiveness of breathing re-training in the treatment of patients with
      asthma. SEARCH STRATEGY: Trials were searched for in the Cochrane Airways Group
      trials register, Cochrane Complementary Medicine Field trials register, EMBASE:
      Physical Medicine & Rehabilitation Field, and Databases of the physiotherapy
      library of current research, World Congress of Physical Therapy Proceedings
      (1995) and AMED (Allied & Alternative Medicine). Hand searching of the
      Association of Chartered Physiotherapists in Respiratory Care Journals was
      undertaken. Chartered physiotherapists in the field of respiratory medicine were
      contacted and appeals made in the 'Physiotherapy' Journal and the Physiotherapy
      Respiratory Care magazine. SELECTION CRITERIA: Randomised or quasi randomised
      controlled trials of breathing re-training in patients of all ages with a
      diagnosis of asthma. Breathing re-training should be a major component of the
      treatment intervention. DATA COLLECTION AND ANALYSIS: Two reviewers (EH & FR)
      independently assessed trial quality and extracted data. Study authors were
      contacted for additional information. Information on adverse effects was
      collected from the included trials where possible. MAIN RESULTS: Abstracts were
      identified and 32 full text papers were obtained for assessment and possible
      inclusion of studies in the review. Twenty seven papers were excluded. A total of
      five papers were included in this review. Most were small. One large study (106
      patients) showed an improvement in PEFR and reduction in rescue bronchodilator
      use. Otherwise benefit of breathing exercises was found in isolated outcome
      measures in single small studies. REVIEWER'S CONCLUSIONS: No reliable conclusions
      can be drawn concerning the use of breathing exercises for asthma in clinical
      practice.

PMID- 10908490
TI  - Interventions for preventing tobacco smoking in public places.
AB  - BACKGROUND: Environmental tobacco smoke is a health hazard. Reducing exposure to
      tobacco smoke in public places is a widespread public health goal. There is,
      however, considerable variation in the extent to which this goal has been
      achieved in different settings and societies. There is therefore a need to
      identify effective strategies for reducing tobacco consumption in public places.
      OBJECTIVES: To evaluate the effectiveness of interventions to reduce tobacco
      consumption in public places. SEARCH STRATEGY: We searched the Tobacco Addiction
      Review Group trials register, Medline, EMBASE, HEALTHSTAR, PAIS, and CDP File
      (National Centre for Chronic Disease Prevention and Health Promotion, CDC)
      "Smoking and Health database". We handsearched a key journal and abstracts from
      international conferences on tobacco. We checked the bibliographies of identified
      studies and reviews for additional references. SELECTION CRITERIA: We considered
      randomized and controlled trials, controlled before and after studies and
      interrupted time series, and uncontrolled before and after studies. We considered
      strategies aimed at populations, including education campaigns, written material,
      non-smoking and warning signs, and comprehensive strategies. We also considered
      strategies aimed at individual smokers. DATA COLLECTION AND ANALYSIS: Information
      relating to the characteristics and content of all kinds of interventions,
      participants, outcomes and methods of the study was abstracted by one reviewer
      and checked by two others. Studies were combined using qualitative narrative
      synthesis. MAIN RESULTS: Eleven of 22 studies reporting information about
      interventions to reduce smoking in public places met all the inclusion criteria.
      All included studies were uncontrolled before and after studies. The most
      effective strategies used comprehensive, multicomponent approaches to implement
      policies banning smoking within institutions. Less comprehensive strategies, such
      as posted warnings and educational material had a moderate effect. Five studies
      showed that prompting individual smokers had an immediate effect, but such
      strategies are unlikely to be acceptable as a public health intervention.
      REVIEWER'S CONCLUSIONS: Carefully planned and resourced, multicomponent
      strategies effectively reduced smoking within public places. Less comprehensive
      strategies were less effective. All the studies used relatively weak experimental
      designs. Most studies were done in the USA, and there is a need to identify ways
      in which these strategies can be adopted and used in countries with different
      attitudes to tobacco use. Future studies should also consider the use of more
      rigorous experimental designs.

PMID- 10908491
TI  - Liquid and fluid agents for preventing adhesions after surgery for subfertility.
AB  - BACKGROUND: Pelvic surgery is associated with high rates of both de novo adhesion
      formation and adhesion reformation. Although the role of pelvic and/or tubal
      surgery in the management of infertility is more limited since the development of
      in-vitro fertilisation such surgery remains indicated for a number of selected
      patients. Other forms of pelvic surgery will remain prevalent in women of
      reproductive age (e.g. endometriosis surgery, ovarian cystectomy, myomectomy).
      Since subsequent fertility is reduced with increasing severity of periadnexal
      adhesions, pelvic adhesions will remain a clinical problem in infertility
      patients. Adjuvant therapy has been promoted for many years to prevent adhesion
      formation. Numerous substances have been used experimentally in animal models,
      many have been advocated for use during human surgery, and some are widely used
      in clinical practice. Steroids and antihistamines are given in the belief that
      they will promote fibrinolysis during healing without preventing healing.
      OBJECTIVES: To investigate whether pharmacological and liquid agents used as
      adjuvants during pelvic surgery in infertility patients lead to a reduction in
      the incidence or severity of postoperative adhesion (re-)formation, and/or an
      improvement in subsequent pregnancy rates. SEARCH STRATEGY: The specialised
      database of the Menstrual Disorders and Subfertility Group was searched.
      SELECTION CRITERIA: Randomised controlled trials investigating the use of
      pharmacological and liquid agents to prevent adhesion formation after pelvic
      surgery for infertility. DATA COLLECTION AND ANALYSIS: Data were extracted
      independently by the first 2 authors. Differences of opinion were registered and
      resolved by consensus with the senior author (RJL). Two by two tables were
      generated for each trial for the dichotomous outcome of pregnancy and the effects
      on pregnancy rate of each study is expressed as an odds ratio with 95% confidence
      intervals. MAIN RESULTS: None of the pharmacological or liquid agents
      investigated in a randomised controlled fashion was shown to improve
      postoperative pregnancy rates. There was some evidence that steroids reduced the
      incidence and severity of postoperative adhesion formation. Dextran appeared to
      neither reduce the incidence or severity of adhesions. REVIEWER'S CONCLUSIONS:
      The routine use of pharmacological agents to prevent post-operative adhesions
      after infertility surgery cannot be recommended on the basis of the available
      evidence derived from RCTs. In connection with adhesion prevention, the evidence
      with regard to steroids is far from perfect but tentatively suggests that they
      may be beneficial. Further randomised studies should be conducted to investigate
      this further.

PMID- 10908492
TI  - Surgery for lumbar disc prolapse.
AB  - BACKGROUND: Surgical investigations and interventions account for as much as one
      third of the health care costs for spinal disorders, but the scientific evidence
      for most procedures is still unclear. OBJECTIVES: The primary rationale for
      surgery for disc prolapse is to relieve nerve root irritation or compression due
      to herniated disc material. Claims of the merits of alternative surgical
      procedures are made without clear evidence about clinical outcomes. The objective
      of this review was to assess the effects of surgical interventions for the
      treatment of lumbar disc prolapse. SEARCH STRATEGY: We have searched the Cochrane
      Controlled Trials Register, Medline, Embase, Biosis, Dissertation Abstracts,
      Index to UK Thesis, and reference lists of the retrieved articles. We have also
      sought trials from expert spinal surgeons and other health workers by direct
      contact. All data found up to 31/12/99 are included. SELECTION CRITERIA:
      Randomised and quasi-randomised trials of the surgical management of lumbar disc
      prolapse. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and
      extracted data from published papers. Additional information was sought from the
      authors if necessary. MAIN RESULTS: Twenty-seven trials have now been found.
      There were methodological weaknesses in many of the trials. Sixteen of the 27
      trials were of some form of chemonucleolysis. Eleven trials compared different
      surgical techniques, although only one of these compared surgical discectomy with
      conservative management. Surgical discectomy produced better clinical outcomes
      than chemonucleolysis with chymopapain, and chemonucleolysis produced better
      clinical outcomes than placebo. Three trials showed no difference in clinical
      outcomes between microdiscectomy and standard discectomy. A recent trial suggests
      that an inter-position gel covering the spinal dura after discectomy may reduce
      scar formation, although both this trial and two others failed to show any
      definite improvement in clinical outcomes. Three trials of percutaneous
      discectomy provided moderate evidence that it produces poorer clinical outcomes
      than standard discectomy or chymopapain. We found no published randomised trials
      of laser discectomy. REVIEWER'S CONCLUSIONS: Chemonucleolysis is more effective
      than placebo and it is less invasive, but less effective than surgical disectomy.
      Surgical discectomy for carefully selected patients with sciatica due to lumbar
      disc prolapse provides faster relief from the acute attack than conservative
      management, although any positive or negative effects on the lifetime natural
      history of the underlying disc disease are unclear.

PMID- 10908493
TI  - Surgery for degenerative lumbar spondylosis.
AB  - BACKGROUND: Surgical investigations and interventions account for as much as one
      third of the health care costs for spinal disorders, but the scientific evidence
      for most procedures is still unclear. OBJECTIVES: Degenerative conditions
      affecting the lumbar spine are variously described as lumbar spondylosis or
      degenerative disc disease (which we regarded as one entity) and are associated
      with back pain, instability, spinal stenosis and degenerative spondylolisthesis.
      The objective of this review was to assess the effects of surgical interventions
      for the treatment of degenerative lumbar spondylosis. SEARCH STRATEGY: We
      searched the Cochrane Controlled Trials Register, Medline, Embase, Biosis,
      Dissertation Abstracts, Index to UK Thesis, and reference lists of the retrieved
      articles and we corresponded with experts. All data found up to 31/12/99 are
      included. SELECTION CRITERIA: Randomised or quasi-randomised trials of surgical
      treatment of lumbar spondylosis DATA COLLECTION AND ANALYSIS: Two reviewers
      assessed trial quality and extracted data from published papers. Additional
      information was sought from the authors if necessary. MAIN RESULTS: Sixteen
      published trials of all forms of surgical treatment for degenerative lumbar
      spondylosis have been identified. There were many serious weaknesses of trial
      design, including poor methods of randomisation, lack of blinding and lack of
      independent assessment of outcome which at times gave considerable potential for
      bias. Most of the published results were reporting on technical surgical outcomes
      with some crude ratings of clinical outcome, but few patient-centred outcomes of
      pain, disability or capacity for work. There was a particular lack of long-term
      outcomes. This review found no published trials comparing any form of surgery for
      degenerative lumbar spondylosis compared with natural history, placebo, or any
      form of conservative treatment. Ten trials randomly compared instrumented and non
      instrumented fusion. Instrumented fusion produced a higher fusion rate (though
      that needs to be qualified by the difficulty of assessing fusion in the presence
      of metal-work) but did not improve clinical outcomes and there is evidence that
      it may be associated with higher complication rates. The few and heterogeneous
      trials on spondylolisthesis, spinal stenosis and nerve compression permitted very
      limited conclusions. REVIEWER'S CONCLUSIONS: There is no scientific evidence
      about the effectiveness of any form of surgical decompression or fusion for
      degenerative lumbar spondylosis compared with natural history, placebo, or
      conservative treatment.

PMID- 10908494
TI  - Duration of treatment with vitamin K antagonists in symptomatic venous
      thromboembolism.
AB  - BACKGROUND: Currently the most frequently used secondary treatment for patients
      with venous thromboembolism are vitamin K antagonists targeted at an INR of 2.5
      (range 2.0 - 3.0). However, based on the continuing risk of bleeding and
      uncertainty regarding the risk of recurrent venous thromboembolism, there is
      discussion on the proper duration of treatment with vitamin K antagonists for
      these patients. Recently, several studies were published in which the risk and
      benefits of different durations of oral anticoagulants were compared in patients
      with venous thromboembolism. OBJECTIVES: The objective of this review was to
      evaluate efficacy and safety of different durations of treatment with vitamin K
      antagonists in patients with symptomatic venous thromboembolism. SEARCH STRATEGY:
      The reviewers sought publications through computerized searches of MEDLINE and
      EMBASE, and by hand-searching relevant journals, using the search strategy
      described by the Cochrane Review Group on Peripheral Vascular Diseases. They also
      contacted colleagues. SELECTION CRITERIA: Randomized controlled clinical trials
      comparing different durations of treatment with vitamin K antagonists in patients
      with symptomatic venous thromboembolism. DATA COLLECTION AND ANALYSIS: Two
      reviewers extracted the data and assessed the quality of the trials
      independently. MAIN RESULTS: Four studies with a total of exactly 1500 patients
      were included. A consistent reduction for the risk of recurrent events was
      observed during prolonged treatment with vitamin K antagonists (OR 0.15; 95% CI
      [0.10 - 0.23]) independent of the period elapsed since the index thrombotic
      event. A 'rebound' phenomenon, i.e. an excess of recurrences shortly after
      cessation of the prolonged treatment was not observed (OR 1.11; 95% CI [0.71 -
      1.75]). In addition, a substantial increase in bleeding complications was found
      during the entire period after randomization (OR 7.75; 95% CI [1.08 - 55.57]).
      REVIEWER'S CONCLUSIONS: In conclusion this meta-analysis shows that treatment
      with vitamin K antagonists reduces the risk of recurrent venous thromboembolism
      as long as it is used. However, the absolute risk of recurrent venous
      thromboembolism declines over time, while the risk for major bleeding remains.
      Thus, the efficiency of vitamin K antagonist administration decreases over time
      since the index event.

PMID- 10908495
TI  - Gabapentin add-on for drug-resistant partial epilepsy.
AB  - BACKGROUND: The majority of patients with epilepsy have a good prognosis and
      their seizures are well controlled by a single antiepileptic drug, but up to 30%
      develop refractory epilepsy, especially those with partial seizures. In this
      review we summarise the current evidence regarding a new antiepileptic drug,
      gabapentin, when used as an add-on treatment for drug-resistant partial epilepsy.
      OBJECTIVES: To evaluate the efficacy and tolerability of gabapentin when used as
      an add-on treatment for patients with drug-resistant partial epilepsy. SEARCH
      STRATEGY: We searched the Cochrane Epilepsy Group's trial register, the Cochrane
      Controlled Trials Register (The Cochrane Library Issue 1, 2000). In addition, we
      contacted Parke Davis (manufacturers of gabapentin) and experts in the field to
      seek any ongoing studies or unpublished studies. SELECTION CRITERIA: Randomized
      placebo controlled double blind add-on trials of gabapentin in patients with drug
      resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently selected trials for inclusion and extracted the relevant data. The
      following outcomes were assessed: (a) 50% or greater reduction in seizure
      frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary
      analyses were intention to treat. Sensitivity best and worst case analyses were
      also undertaken. Summary odds ratios were estimated for each outcome. Dose
      response was evaluated in regression models, and Number Needed to Treat (NNTs)
      were calculated for individual doses. MAIN RESULTS: Five trials were included
      representing 997 randomized patients. Overall odds ratio (OR) (95% Confidence
      Interval (CI)) for 50% or greater reduction in seizure frequency compared to
      placebo was 1.93 (1.37 - 2.71). Dose regression analysis shows increasing
      efficacy with increasing dose, with 28.5% (21.5 - 36.7) of patients responding to
      1800mg of gabapentin compared to placebo, NNT 6.7 (3.0 - 10.5). Treatment
      withdrawal OR (95% CI) compared to placebo 1.05 (0.68 - 1.61); Side effects: OR
      (99% CI) compared to placebo. Dizziness 2.22 (1.28 - 3. 85); fatigue 2.28 (1.15 -
      4.52); somnolence 2.01 (1.24 - 3.28) were significantly associated with
      gabapentin. REVIEWER'S CONCLUSIONS: Gabapentin has efficacy as an add-on
      treatment in patients with drug-resistant partial epilepsy. However, trials
      reviewed were of relatively short duration, and provide no evidence for the long
      term efficacy of gabapentin. Results cannot be extrapolated to monotherapy or
      patients with other epilepsy types.

PMID- 10908496
TI  - Immunotherapy for advanced renal cell cancer.
AB  - BACKGROUND: The course of advanced renal cell carcinoma is extremely variable,
      ranging from spontaneous remission to disease progression refractory to
      chemotherapy. Immunotherapy has held promise of improved outcomes based on
      uncontrolled studies and randomized controlled trials generally limited by small
      size and low power. OBJECTIVES: To evaluate immunotherapy for advanced renal cell
      carcinoma by comparing: (1) high dose interleukin-2 to other options and (2)
      interferon-alpha to other options. SEARCH STRATEGY: A search of MEDLINE,
      Cancerlit, EMBASE and Cochrane Library databases from 1966 through the end of
      1999. Handsearches were made of the proceedings of the annual meetings of the
      American Urologic Association, ASCO, and biennial European ECCO meetings, and the
      references of identified studies. SELECTION CRITERIA: Randomized controlled
      trials that selected (or stratified) patients with advanced renal cell carcinoma,
      utilized an immunotherapeutic agent in at least one study arm, and reported
      response or survival by allocation. Forty-two studies involving 4216 patients
      were eligible and reported response and 26 of these reported survival outcome
      (3089 patients). DATA COLLECTION AND ANALYSIS: Two independent reviewers
      abstracted each article by following a prospectively designed protocol.
      Dichotomous outcomes for treatment response (partial plus complete) and for
      deaths at one year were used for the main comparisons. Survival hazard ratios
      were also used for studies of interferon-alpha versus controls. MAIN RESULTS: The
      average response rate was 10.2 % (range by arm, 0 - 39%) and complete response
      rate was 3.2% (123/3852; n = 38 studies). Median survival averaged 11.6 months
      (range by arm, 6 - 28 months) and two-year survival averaged 22% (16 studies,
      range by arm 8 - 41%). There were no placebo-controlled studies and no randomized
      controlled studies examined survival for high dose interleukin-2 versus controls.
      Results from 6 studies (n = 963) indicate that interferon-alpha is superior to
      controls (OR for death at one year = 0.67, 95% CI 0.50 - 0.89. The pooled hazard
      ratio for survival of 0.78 (0.67 - 0.90) indicates that the treatment effect
      persisted until 24 months from randomization. The weighted average median
      improvement in survival was 2.6 months. Additional comparisons failed to prove a
      survival benefit from the addition of other agents to either modified schedules
      of interleukin-2 or to interferon-alpha. Dose-response studies examining survival
      for either agent could not be identified. The difference in response rate between
      arms was correlated with the difference in survival (P<0.001) suggesting that
      response rate difference may be a surrogate intermediate endpoint for survival.
      REVIEWER'S CONCLUSIONS: Interferon-alpha provides a modest survival benefit
      compared to other commonly used treatments and should be considered for the
      control arm of future studies of systemic agents. Interleukin-2 has not been
      validated in controlled randomized studies.

PMID- 10908497
TI  - Patient support and education for promoting adherence to highly active
      antiretroviral therapy for HIV/AIDS.
AB  - BACKGROUND: Highly active antiretroviral therapy is associated with improved
      health outcomes for people living with HIV/AIDS. Unfortunately, full therapeutic
      benefit from HAART may require near-perfect adherence to prescribed regimens.
      OBJECTIVES: To determine the effectiveness of patient support and education
      interventions for improving adherence to highly active antiretroviral therapy
      (HAART) in people living with HIV and AIDS. SEARCH STRATEGY: Studies were
      identified using AIDSLINE, MEDLINE, CINAHL, HEALTHSTAR, PSYCHLIT, SOCIOLOGICAL
      ABSTRACTS, INTERNATIONAL PHARMACEUTICAL ABSTRACTS, SCIENCE CITATION INDEX,
      EMBASE, and abstracts from global AIDS meetings, ICAAC, and other major meetings
      from January 1996 to April 1999. Further information was sought through contact
      with authors, reference lists, and Collaborative Review Group databases.
      SELECTION CRITERIA: To be included, studies had to describe a supportive or
      educational intervention to improve adherence to a HAART regimen in HIV positive
      patients, and include a comparison group. Eligible HAART regimens were defined as
      consisting of at least three anti-HIV drugs one of which must be a protease
      inhibitor or non-nucleoside reverse transcriptase inhibitor. At least one measure
      of adherence was also required. DATA COLLECTION AND ANALYSIS: Data on study
      design, participants, interventions, and outcomes were extracted from the reports
      onto specifically designed data collection forms by at least two reviewers. MAIN
      RESULTS: One study satisfied the eligibility criteria. It compared a pharmacist
      led intervention consisting of educational counseling and availability of follow
      up telephone support with conventional dispensing of HAART pills. This
      intervention significantly improved adherence to HAART, and adherence to HAART
      significantly predicted undetectable viral load at 24 weeks. However,
      participating in the intervention did not significantly predict a subsequently
      undetectable viral load at 24 weeks. REVIEWER'S CONCLUSIONS: Implications for
      practice Currently a pharmacist-led program of educational and supportive
      counseling is the only available intervention which has been shown in a
      controlled study to improve adherence to HAART, with less evidence that viral
      load is subsequently reduced. Implications for research Controlled trials are
      urgently needed to determine which interventions can significantly improve
      adherence to HAART. Whether interventions that improve adherence also suppress
      viral load and improve clinical outcomes should also be considered.

PMID- 10908498
TI  - Corticosteroids for treating Guillain-Barre syndrome.
AB  - BACKGROUND: The cause of Guillain-Barre syndrome (GBS) is inflammation of the
      peripheral nerves which corticosteroids would be expected to benefit. OBJECTIVES:
      To examine the efficacy of corticosteroids in hastening recovery and reducing the
      long term morbidity from Guillain-Barre syndrome (GBS). SEARCH STRATEGY: Search
      of the Cochrane Neuromuscular Disease Group register for randomised trials and
      enquiry from authors of trials and other experts in the field. SELECTION
      CRITERIA: Types of studies: quasi-randomised or randomised controlled trials
      TYPES OF PARTICIPANTS: patients with GBS of all ages and all degrees of severity
      Types of interventions: any form of corticosteroid or adrenocorticotrophic
      hormone Types of outcome measures: Primary: improvement in disability grade on a
      commonly used seven point scale four weeks after randomisation Secondary: time
      from randomisation until recovery of unaided walking, time from randomisation
      until discontinuation of ventilation (for those ventilated), mortality,
      proportion of patients dead or disabled (unable to walk without aid) after 12
      months, improvement in disability grade after six months, improvement in
      disability grade after 12 months, proportion of patients who relapse, and
      proportion of patients with adverse events related to corticosteroid treatment
      DATA COLLECTION AND ANALYSIS: We identified six randomised trials. One author
      extracted the data and the other checked them. We obtained some missing data from
      investigators. MAIN RESULTS: The six eligible trials included a total of 195
      corticosteroid treated patients and 187 control subjects. One trial of
      intravenous methylprednisolone accounted for 243 of the total 382 subjects
      studied (63%). This trial did not show a significant difference in any disability
      related outcome between the corticosteroid and placebo groups. There was no
      significant difference between the corticosteroid and control groups for the
      primary outcome measure, improvement in disability grade four weeks after
      randomisation. The weighted mean difference of the three trials for which this
      outcome was available showed no difference. The actual figure was 0.01 (95% CI 
      0.27 to 0.29) grade in favour of the corticosteroid group. There was also no
      significant difference between the groups for most of the secondary outcome
      measures. However in the largest trial hypertension developed less often in the
      intravenous methylprednisolone group (2/124, 1.6%) than in the control group
      (12/118, 10.2%), a significant difference in favour of corticosteroid treatment
      (relative risk 0.20, 95% CI 0.04 to 0.66). REVIEWER'S CONCLUSIONS:
      Corticosteroids should not be used in the treatment of Guillain-Barre syndrome.
      If a patient with Guillain-Barre syndrome needs corticosteroid treatment for some
      other reason its use will probably not do harm. The effect of intravenous
      methylprednisolone combined with intravenous immunoglobulin in Guillain-Barre
      syndrome is being tested with a randomised trial.

PMID- 10908499
TI  - Token economy for schizophrenia.
AB  - BACKGROUND: A token economy is a behavioural therapy technique in which the
      desired change is achieved by means of tokens administered for the performance of
      predefined behaviours according to a program. Though token economy programmes
      were widespread in the 1970s they became largely restricted to wards where long
      stay patients from institutions are prepared for transfer into the community and
      were particularly aimed at changing negative symptoms of schizophrenia - poor
      motivation, poor attention and social withdrawal. OBJECTIVES: To review the
      effects of token economies for people with schizophrenia, or other serious or
      chronic mental illnesses, compared with standard care. SEARCH STRATEGY:
      Electronic searches of Biological Abstracts (1985-1999), CINAHL (1982-1998), The
      Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register of
      Trials (February 1999), EMBASE (1980-1999) and PsycLIT (1987-1998) were
      supplemented with reference searches, personal contact with trial authors and
      hand searches. SELECTION CRITERIA: Randomised studies comparing a token economy
      regime (one in which change is achieved by means of use of non-monetary, non
      consumable tokens) to standard care for those with schizophrenia or any other
      similar chronic or serious mental illness. DATA COLLECTION AND ANALYSIS: Studies
      were reliably selected, quality rated and data extracted. For dichotomous data
      relative risk (RR) with 95% confidence intervals (CI) was estimated. Where
      possible, the number needed to treat statistic (NNT) was also calculated.
      Analysis was by intention-to-treat. Normal continuous data were summated using
      the weighted mean difference (WMD). Scale data were presented only for those
      tools that had attained pre-specified levels of quality. MAIN RESULTS: Only three
      randomised controlled trials could be included in the analyses (total n=110).
      There were no usable data on target or non-target behaviour. One small study
      favoured the token economy approach for the outcome 'change in mental state' on
      the SANS-CV with improvement in negative symptoms at three months (n=40, WMD -12.
      7, CI -21.44 to -3.96). REVIEWER'S CONCLUSIONS: The token economy approach may
      have effects on negative symptoms but it is unclear if these results are
      reproducible, clinically meaningful and are maintained beyond the treatment
      programme. Token economy remains worthy of careful evaluation in well designed,
      conducted and reported randomised trials.

PMID- 10908500
TI  - Antibiotics for preventing pneumonia in children with measles.
AB  - BACKGROUND: Measles causes more than a million deaths a year, of which most are
      children under five years of age who die from pneumonia. OBJECTIVES: The
      objective of this review was to assess the effects of antibiotics given to
      children with measles on reducing pneumonia or mortality, and to assess whether
      antibiotics should be given to all children with measles in communities with a
      high fatality rate. SEARCH STRATEGY: We searched MEDLINE (1966 - 1999), EMBASE
      (1980-1999) and the specialized trials register of the Acute Respiratory
      Infections Group in August 1999, and all relevant journals in the University of
      Melbourne medical library for the years 1935-46. SELECTION CRITERIA: Randomised
      or controlled trials of antibiotics for children with measles. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently extracted data and assessed trial
      quality. MAIN RESULTS: Six trials with 1304 children were included. All but one
      of the trials were unblinded, and randomisation was either not described or was
      by alternate allocation. In four studies, the incidence of pneumonia in the
      control group was similar to that in the antibiotic prophylaxis group; in the
      other two studies, the incidence of pneumonia was unusually high in the control
      group so these children had a higher complication rate than the antibiotic group.
      Four of the 764 children given antibiotics died compared with one of the 637
      controls. REVIEWER'S CONCLUSIONS: The quality of the trials reviewed was poor,
      and they provide very weak evidence for giving antibiotics to all children with
      measles. Available evidence suggests that antibiotics should be given only if a
      child has clinical signs of pneumonia or other evidence of sepsis.

PMID- 10908501
TI  - Elastic compression stockings for prevention of deep vein thrombosis.
AB  - BACKGROUND: One of the settings in which deep vein thrombosis (DVT) in the lower
      limb and pelvic veins occurs is prolonged immobilisation in hospital for various
      surgical and medical illnesses. Use of graduated compression stockings (GCS) in
      these patients has been proposed to decrease the risk of DVT. OBJECTIVES: The
      objective of this review was to determine the magnitude of effectiveness of GCS
      in preventing DVT in various groups of hospitalised patients. SEARCH STRATEGY:
      The reviewers searched the Cochrane Peripheral Vascular Disease Group trials
      register, MEDLINE, and EMBASE and hand searched Indexes Medicus. Various GCS
      manufacturing companies and the trialists in the ongoing trials were contacted.
      SELECTION CRITERIA: Randomised controlled trials (RCT's) involving:. Graduated
      compression stockings alone. Graduated compression stockings used on a background
      of any other DVT prophylactic method. DATA COLLECTION AND ANALYSIS: One reviewer
      extracted the data, assessed the quality of trials and analysed the results (SVA)
      this was cross-checked and authenticated by the other reviewer (TAL). MAIN
      RESULTS: A total of 16 RCTs were identified. GCS were applied on the day before
      surgery or on the day of surgery. GCS were worn up until discharge or until the
      patients were fully mobile. In the majority of the included studies, DVT was
      identified by radioactive I 125 uptake test. GCS alone. Nine RCTs were identified
      in this group. In the treatment group (GCS) of 624 patients, 81 developed DVT
      (13%) in comparison to the control group of 581 patients, where 154 (27%) had
      DVT, Peto's odds ratio 0.34 (95% confidence interval 0.25, 0.46) favouring
      treatment with GCS. GCS on a background of another prophylactic method. Seven
      RCTs were identified this group. In the treatment group (GCS + another method) of
      501 patients, 10 (2%) developed DVT whereas in the control group of 505 patients,
      74 (15%) developed DVT, Peto's odds ratio 0.24 (95% confidence interval 0.15,
      0.37). REVIEWER'S CONCLUSIONS: Analysis of these RCT's confirm that GCS are
      effective in diminishing the risk of DVT in hospitalised patients. Data
      examination also suggests, that GCS on a background of another method of
      prophylaxis is even more effective than GCS alone.

PMID- 10908502
TI  - Short-acting beta 2 agonists for stable COPD.
AB  - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterised by
      progressive airflow limitation that is at best partially reversible. Despite the
      lack of reversibility patients with stable often report symptomatic improvement
      with short-acting beta-2 bronchodilator medication. OBJECTIVES: To determine the
      clinical effectiveness and assess the adverse effects of regular treatment with
      short-acting beta-2 agonists bronchodilators in patients with stable COPD. SEARCH
      STRATEGY: A search was carried out using the Cochrane Airways Group database. In
      addition, reference lists of review articles and retrieved studies were searched
      for other potentially relevant citations. SELECTION CRITERIA: Randomised
      controlled trials of at least one week in duration that compared treatment with
      inhaled short-acting beta-2 agonists delivered by metered dose inhaler or
      nebuliser with placebo in patients with stable COPD. DATA COLLECTION AND
      ANALYSIS: Data extraction and study quality assessment were performed
      independently by two reviewers. Where further or missing data was required,
      authors of studies were contacted. The data were analysed using the Cochrane
      Review Manager 4.0.4. MAIN RESULTS: Thirteen studies were included. All used a
      cross-over design and were of high quality. Post-bronchilator spirometry
      performed at the end of the study period showed a significant increase in FEV1
      compared to placebo; weighted mean difference (WMD) =0.14 L; 95% Confidence
      Interval (CI) 0.04 to 0.25. This effect was only seen in studies in which the
      drug was delivered by metered dose inhaler. Post-bronchodilator morning and
      evening PEFR were significantly better during active treatment than during
      placebo; WMD=29.2 L/min; 95%CI 0.3 to 58.1 & WMD = 36.8 L/min; 95%CI: 2.6 to 70.9
      respectively. A significant improvement in daily breathlessness score was
      observed during treatment with beta-2 agonist when compared to placebo;
      standardised mean difference (SMD) =1.33; 95%CI: 1.0 to 1.65. There was no
      improvement in exercise performance. The risk of dropping out of the study (ie
      treatment failure) when on treatment with placebo was almost twice that of
      patients on treatment with beta-2 agonists; Relative Risk =0.49; 95%CI 0.33
      0.73). Patients preferred beta-2 agonist therapy more frequently than placebo;
      Odds Ratio = 9.04; 95%CI 4.6 to 17.61). No studies reported serious side effects
      during treatment with inhaled beta-agonists, but none were of sufficient size or
      length to allow any meaningful information on long-term occurrence of side
      effects. REVIEWER'S CONCLUSIONS: Short-acting beta-2 agonists delivered by
      metered dose inhaler on a regular basis improve lung function. Breathlessness but
      not exercise performance are also improved. There are insufficient data to
      provide reliable information on long-term adverse effects. Use of these drugs as
      first line agents for symptomatic treatment of COPD is supported by this review.

PMID- 10908503
TI  - Ropinirole for levodopa-induced complications in Parkinson's disease.
AB  - BACKGROUND: Long-term levodopa therapy for Parkinson's disease is complicated by
      the development of motor fluctuations and abnormal involuntary movements. One
      approach is to add a dopamine agonist at this stage of the disease to reduce the
      time the patient spends immobile or off and to reduce the dose of levodopa in the
      hope of reducing such problems in the future. OBJECTIVES: To compare the efficacy
      and safety of adjuvant ropinirole therapy versus placebo in patients with
      Parkinson's disease already established on levodopa therapy and suffering from
      motor complications. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and
      the Cochrane Controlled Trials Register. Handsearching of the neurology
      literature as part of the Cochrane Movement Disorders Group's strategy.
      Examination of the reference lists of identified studies and other reviews.
      Contact with SmithKline Beecham. SELECTION CRITERIA: Randomised controlled trials
      of ropinirole versus placebo in patients with a clinical diagnosis of idiopathic
      Parkinson's disease and long-term complications of levodopa therapy. DATA
      COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and
      differences settled by discussion. The outcome measures used included Parkinson's
      disease rating scales, levodopa dosage, 'off' time measurements and the frequency
      of withdrawals and adverse events. MAIN RESULTS: Three double-blind, parallel
      group, randomised, controlled trials have been conducted on 263 patients. The two
      phase II studies were relatively small, were conducted over the short term (12
      weeks), and used relatively low doses of ropinirole. The other phase III study
      was medium term (26 weeks) and used ropinirole doses in line with the current UK
      licensed maximum. Additional data from the manufacturer showed that the
      difference in the reduction in off time was non-significantly greater with
      ropinirole than placebo (weighted mean difference [WMD] 0.19 hours; -0.63, 1.00
      95% CI). As an adverse event, dyskinesia was significantly increased in those who
      received ropinirole (odds ratio [OR] 2.59; 1.35, 4.96 95% CI; p < 0.004).
      Measurements of motor impairments and disability were poor in these studies with
      incomplete information available. Levodopa dose could be reduced in two studies
      with a significantly larger reduction on ropinirole than on placebo (WMD
      136.5mg/d; 74.5, 198.6 95% CI; p =0.00002). No significant differences in the
      frequency of adverse event reports were noted between ropinirole and placebo
      apart from the increase in dyskinesia with ropinirole. There was a trend towards
      fewer withdrawals from ropinirole but this did not reach statistical
      significance. REVIEWER'S CONCLUSIONS: Ropinirole therapy can reduce levodopa dose
      but at the expense of increased dyskinetic adverse events. No significant effect
      on off time reduction was found but this may have been due to under-powered
      trials and the low doses of ropinirole used in the phase II studies. Inadequate
      data on motor impairments and disability was collected to assess these outcomes.
      These conclusions apply to short and medium term treatment, up to 26 weeks.
      Further longer term trials are required, with measurements of effectiveness, and
      also studies to compare the newer with the older dopamine agonists.

PMID- 10908504
TI  - Ropinirole versus bromocriptine for levodopa-induced complications in Parkinson's
      disease.
AB  - BACKGROUND: Long-term levodopa therapy for Parkinson's disease is complicated by
      the development of motor fluctuations and abnormal involuntary movements. One
      approach is to add a dopamine agonist at this stage of the disease to reduce the
      time the patient spends immobile or off and to reduce the dose of levodopa in the
      hope of reducing such problems in the future. OBJECTIVES: To compare the efficacy
      and safety of adjuvant ropinirole therapy with bromocriptine in patients with
      Parkinson's disease already established on levodopa therapy and suffering from
      motor complications. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and
      the Cochrane Controlled Trials Register. Handsearching of the neurology
      literature as part of the Cochrane Movement Disorders Group's strategy.
      Examination of the reference lists of identified studies and other reviews.
      Contact with SmithKline Beecham. SELECTION CRITERIA: Randomised controlled trials
      of ropinirole versus bromocriptine in patients with a clinical diagnosis of
      idiopathic Parkinson's disease and long-term complications of levodopa therapy.
      DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors
      and differences settled by discussion. The outcome measures used included
      Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and
      the frequency of withdrawals and adverse events. MAIN RESULTS: No significant
      differences between ropinirole and bromocriptine were found in off time
      reduction, dyskinesia as an adverse event, motor impairment and disability, or
      levodopa dose reduction. Withdrawal rates and adverse event frequency were
      similar with the two agents apart from significantly less nausea with ropinirole
      (odds ratio 0.50; 0.29, 0. 84 95% CI; p =0.01). REVIEWER'S CONCLUSIONS:
      Ropinirole is at least as good as bromocriptine in patients with Parkinson's
      disease with motor complications in terms of improving off time and reducing
      levodopa dose, without increasing adverse events including dyskinesia. However,
      these comparitor studies may have been underpowered to detect clinically
      meaningful differences between the agonists. Further, much larger, phase IV
      studies are required to examine the efficacy, effectiveness, and safety of all of
      the dopamine agonists as adjuvant therapy in Parkinson's disease.

PMID- 10908505
TI  - Yoga for epilepsy.
AB  - BACKGROUND: Stress is considered an important precipitating factor for seizures.
      Yoga is believed to induce relaxation and stress reduction. The effect of yoga on
      the EEG and the autonomic nervous system have been reported. Yoga would be an
      attractive therapeutic option for epilepsy (if proved effective), in view of its
      nonpharmacological nature, minimal side effects and international acceptance.
      OBJECTIVES: To assess the efficacy of yoga in the treatment of patients with
      epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trial
      register, the Cochrane Controlled Trials Register (The Cochrane Library Issue 4,
      1998), MEDLINE for articles published up to the middle of 1998, and also
      registries of the research council for complimentary medicine were searched. In
      addition, we searched the references of all the identified studies. Finally, we
      contacted the members of the Neurological Society of India, several
      neurophysiology institutions and yoga institutes to seek any ongoing studies or
      studies published in nonindexed journals or unpublished studies. SELECTION
      CRITERIA: Randomized control trials and controlled clinical trials of treatment
      of epilepsy with yoga. DATA COLLECTION AND ANALYSIS: The data were extracted
      independently by both reviewers and any discrepancies were resolved by
      discussion. The main outcomes assessed were percentage of patients rendered
      seizure free, number of patients with more than 50% reduction in seizure
      frequency or seizure duration and the overall reduction in seizure frequency.
      Analyses were on an intention to treat basis. MAIN RESULTS: Only one study met
      the selection criteria, and recruited a total of 32 patients, 10 to sahaja yoga
      and 22 to control treatments. Antiepileptic drugs were continued in all.
      Randomization was by roll of a dice. The results of this study are as follows:
      (i) Four patients treated with yoga were seizure free for six months compared to
      none in the control groups. The Odds Ratio (OR) (95% Confidence Interval (CI))
      for yoga versus sham yoga group was 14.5 (0.7, 316.7) and for yoga versus no
      treatment group 17.3 (0.8, 373.5). (ii) Nine patients in the yoga group had more
      than 50% reduction in seizure frequency compared to only one among the controls.
      The OR (95% CI) for yoga versus sham yoga group was 81 (4.4, 1504.5) and for the
      yoga versus no treatment group was 158.3 (5.8, 4335.9). (iii) There was a decline
      in the average number of attacks per month compared to the baseline frequency
      among the patients treated with yoga. The weighted mean difference ( 95% CI)
      between yoga versus sham yoga group was -2.1 (-3.1, -1.0) and for the yoga versus
      no treatment group -1.1 (-1.8, -0.4). (iv) More than 50% reduction in seizure
      duration was found in seven of the 10 patients treated with yoga, compared to
      none among the 22 controls. The OR (95%CI) for yoga versus sham yoga group was 45
      (2.0, 1006.8) and for yoga versus no treatment group 53.57 (2.4, 1187.3).
      REVIEWER'S CONCLUSIONS: No reliable conclusions can be drawn regarding the
      efficacy of yoga as a treatment for epilepsy. Further studies are necessary to
      evaluate the efficacy of yoga in the treatment of epilepsy.

PMID- 10908506
TI  - Late versus early surgical correction for congenital diaphragmatic hernia in
      newborn infants.
AB  - BACKGROUND: Congenital diaphragmatic hernia, although rare (1 per 2-4,000
      births), is associated with high mortality and cost. Opinion regarding the timing
      of surgical repair has gradually shifted from emergent repair to a policy of
      stabilization using a variety of ventilatory strategies prior to operation.
      Whether delayed surgery is beneficial remains controversial. OBJECTIVES: To
      summarize the available data regarding whether surgical repair in the first 24
      hours after birth rather than later than 24 hours of age improves survival to
      hospital discharge in infants with congenital diaphragmatic hernia who are
      symptomatic at or immediately after birth. SEARCH STRATEGY: Search of Medline
      (1966-1999), Embase (1978-1999) and the Cochrane databases using the terms
      "congenital diaphragmatic hernia" and "surg*"; citations search, and contact with
      experts in the field to locate other published and unpublished studies. SELECTION
      CRITERIA: Studies were eligible for inclusion if they were randomized or quasi
      randomized trials that addressed infants with CDH who were symptomatic at or
      shortly after birth, comparing early (<24 hours) vs late (>24 hours) surgical
      intervention, and evaluated mortality as the primary outcome. DATA COLLECTION AND
      ANALYSIS: Data were collected regarding study methods and outcomes including
      mortality, need for ECMO and duration of ventilation, both from the study reports
      and from personal communication with investigators. Analysis was performed in
      accordance with the standards of the Cochrane Neonatal Review Group. MAIN
      RESULTS: Two trials met the pre-specified inclusion criteria for this review.
      Both were small trials (total n<90) and neither showed any significant difference
      between groups in mortality. Meta-analysis was not performed because of
      significant clinical heterogeneity between the trials. REVIEWER'S CONCLUSIONS:
      There is no clear support for either immediate (within 24 hours of birth) or
      delayed (until stabilized) repair of congenital diaphragmatic hernia, but a
      substantial advantage to either one cannot be ruled out. A large, multicenter
      randomized trial would be needed to answer this question.

PMID- 10908507
TI  - Mobilisation strategies after hip fracture surgery in adults.
AB  - BACKGROUND: Post-operative care programmes after hip fracture surgery include
      strategies for mobilisation, such as early weight bearing, gait retraining and
      other physical therapy interventions. OBJECTIVES: To evaluate the effects of
      different mobilisation strategies and programmes after hip fracture surgery.
      SEARCH STRATEGY: The Cochrane Musculoskeletal Injuries Group trials register,
      Medline, and reference lists of relevant articles were searched. Date of the most
      recent search: August 1999. SELECTION CRITERIA: All randomised or quasi
      randomised trials comparing different mobilisation strategies/programmes after
      hip fracture surgery. DATA COLLECTION AND ANALYSIS: All reviewers independently
      assessed trial quality, using a ten item scale, and extracted data. Wherever
      appropriate and possible, the data are presented graphically. MAIN RESULTS: Each
      of the four included trials evaluated a different intervention. All had poor and
      / or poorly reported trial methodology. One trial of 100 patients compared twice
      daily with once daily physiotherapy. Only limited outcome data were available for
      checking the claims in the trial report that there was no demonstrable difference
      in recovery of the two patient groups at nine weeks follow-up. A treadmill gait
      retraining programme was compared with a conventional gait retraining programme
      in one trial of 40 patients. More patients in the treadmill group had recovered
      their pre-fracture level of mobility by the time of hospital discharge, which
      tended to happen earlier than for the control group. Neither of these differences
      were statistically significant. One trial of 24 patients compared neuromuscular
      stimulation of the quadriceps muscle with placebo stimulation. No data were
      available to test the claims that neuromuscular stimulation improved the recovery
      of mobility, assessed up to 13 weeks. One trial involving 273 patients with a
      displaced intracapsular fracture treated by internal fixation compared weight
      bearing at two weeks after surgery with delayed weight bearing at 12 weeks after
      surgery. From the limited data available, there were no statistically significant
      differences between the two methods of treatment for the outcomes of non-union,
      mortality and overall unfavourable outcome at one year (42/141 versus 50/132;
      relative risk = 0.79, 95%confidence interval = 0.56 to 1.10). REVIEWER'S
      CONCLUSIONS: There is insufficient evidence from randomised trials to determine
      the effects of more frequent physiotherapy, treadmill gait retraining, or
      neuromuscular stimulation after hip fracture surgery. There is also insufficient
      evidence to determine the effects of early weight bearing after the internal
      fixation of an intracapsular proximal femoral fracture.

PMID- 10908508
TI  - Surgical approaches and ancillary techniques for internal fixation of
      intracapsular proximal femoral fractures.
AB  - BACKGROUND: In fixation of intracapsular hip fractures, different implants,
      surgical approaches and ancillary manoeuvres have been employed to improve the
      reduction, and the stability of the reconstruction, in an attempt to reduce the
      frequency of non-union and aseptic necrosis of the femoral head. OBJECTIVES: To
      compare alternative surgical approaches and ancillary techniques in internal
      fixation of intracapsular hip fractures which have been subjected to randomised
      trials in elderly people. SEARCH STRATEGY: The Cochrane Musculoskeletal Injuries
      Group trials register, Medline, and reference lists of relevant articles were
      searched. Date of the most recent search: June 1998. SELECTION CRITERIA: All
      randomised and quasi-randomised trials investigating operative technique for the
      treatment of intracapsular hip fractures. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed trial quality, by use of a ten-item checklist,
      and extracted data. MAIN RESULTS: One study of 94 patients studied the effect of
      impaction of the fracture at the time of surgery. The only outcome measure was
      bone scintimetry. There was no difference in scintimetry for the 29 undisplaced
      fractures but in displaced fractures treated with impaction the scintimetry
      appearances were significantly reduced implying a reduction of blood flow to the
      femoral head. One study of 220 patients compared the results of fractures treated
      with compression against those without compression. Results for 156 patients at
      one year showed a tendency to a lower incidence of non-union for those fractures
      treated without compression. One study of 49 patients noted a tendency to a
      reduced mortality for closed reduction of the fracture as opposed to open
      reduction. Non-union of the fracture was more common after closed reduction.
      REVIEWER'S CONCLUSIONS: Insufficient evidence exists from randomised trials to
      confirm the benefits of open or closed reduction or for intra-operative impaction
      or compression of an intracapsular fracture treated by internal fixation.

PMID- 10908509
TI  - Suburethral sling operations for urinary incontinence in women.
AB  - BACKGROUND: Suburethral slings are surgical operations used to treat women with
      urinary incontinence. They were originally designed for recurrent stress
      incontinence, but have also been used recently for primary cases. OBJECTIVES: To
      determine the effects of suburethral slings on stress or mixed urinary
      incontinence in comparison with other management options. SEARCH STRATEGY: We
      searched the Cochrane Incontinence Group's trials register, The National Research
      Register and the reference lists of relevant articles. We hand searched the
      proceedings of the Brazilian Congress of Urology from 1991 to 1999, inclusive.
      Date of most recent search: January 2000. SELECTION CRITERIA: Randomised or quasi
      randomised trials that included suburethral slings for the treatment of urinary
      incontinence. DATA COLLECTION AND ANALYSIS: Both reviewers independently
      extracted data from included trials onto a standard form and assessed trial
      methodological quality. The data abstracted were relevant to predetermined
      outcome measures. Where appropriate, a summary statistic was calculated: a
      relative risk for dichotomous data and a weighted mean difference for continuous
      data. MAIN RESULTS: Five trials were identified including 206 women - 126 treated
      with suburethral slings and 80 with other procedures. Three compared suburethral
      slings with open abdominal retropubic suspensions (Burch/Marshall-Marchetti
      Krantz) and one compared suburethral slings with needle suspension (Stamey). In
      the fifth trial, different types of suburethral sling were compared with each
      other. Six types of slings were included (Teflon, polytetrafluoroethylene,
      Goretex, porcine dermis, lyophilized dura mater and rectus fascia). There were no
      comparisons of suburethral sling with anterior repair, laparoscopic retropubic
      suspension, peri-urethral injections, artificial sphincters or conservative
      management. There is one ongoing trial with Tension-free Vaginal Tape (TVT)
      versus Burch colposuspension, results expected in August 2000. For each outcome
      data were available only from individual trials. There were no detectable
      differences in terms of voiding dysfunction, urge incontinence or detrusor
      instability between suburethral slings and abdominal or needle suspensions, but
      the data were few and the confidence intervals wide. More peri-operative
      complications were reported after suburethral slings than after needle suspension
      (9/10 vs 2/10; RR 4.5, 95% CI 1.3 to 15.8), and length of stay was longer after
      sling operations than after abdominal or needle suspension. In the trial which
      compared autologous (rectus fascia) with synthetic (Goretex) slings, 11/32 vs
      2/16 women had not improved after a year (RR 2.75, 95% CI 0.69 to 10.95), but
      fewer had complications (0/32 vs 5/16; RR 0.05, 95% CI 0 to 0.8). Two women in
      the second group had late sling erosion of the urethra requiring removal of the
      Goretex, although their incontinence remained cured. REVIEWER'S CONCLUSIONS:
      There were few data available to compare suburethral sling operations with other
      surgical management (abdominal and needle suspension, or different types of
      slings). In general, the quality of trials was poor with no clear method of
      randomisation, small numbers of women studied, short follow-up and scanty
      information on outcome measures. There is not enough evidence on which to judge
      whether suburethral slings are better or worse than other surgical or non
      surgical managements.

PMID- 10908510
TI  - Anterior vaginal repair for urinary incontinence in women.
AB  - BACKGROUND: Anterior vaginal repair (anterior colporrhaphy) is an operation
      traditionally used for moderate or severe stress urinary incontinence in women.
      About a third of adult women experience urinary incontinence. OBJECTIVES: To
      determine the effects of anterior vaginal repair (anterior colporrhaphy) on
      stress or mixed urinary incontinence in comparison with other management options.
      SEARCH STRATEGY: We searched the Cochrane Incontinence Group's trials register,
      and the reference lists of relevant articles. Date of most recent search: May
      2000. SELECTION CRITERIA: Randomised or quasi-randomised trials that included
      anterior vaginal repair for the treatment of urinary incontinence. DATA
      COLLECTION AND ANALYSIS: Both reviewers independently extracted data and assessed
      trial quality. Two trial investigators were contacted for additional information.
      MAIN RESULTS: Seven trials were identified which included 252 women having an
      anterior vaginal repair and 517 who received comparison interventions. A single
      small trial provided insufficient evidence to assess anterior repair in
      comparison with physical therapy. The performance of anterior repair in
      comparison with needle suspension appeared similar but clinically important
      differences could not be confidently ruled out. No trials compared anterior
      repair with suburethral sling operations or laparoscopic retropubic suspensions,
      or compared alternative vaginal operations. Anterior repair was less effective
      than open abdominal retropubic suspension based on patient-reported cure rates in
      six trials both in the short-term (failure rate within first year after anterior
      repair 48/198, 24% vs 30/266, 11%; RR 2.15, 95% CI 1.40 to 3.28) and long-term
      (after first year, 109/242, 45% vs 57/315, 18%; RR 2.63, 1. 98 to 3.49). There
      was evidence from two of these trials that this was reflected in more repeat
      operations for incontinence (16/83, 19% vs 4/140, 2.9%; RR 7.12, 2.53 to 20.07).
      These findings held irrespective of the co-existence of prolapse (pelvic
      relaxation). Later prolapse operation appeared to be equally common after vaginal
      (3.6%) or abdominal (3.6%) operation. In respect of the type of open abdominal
      retropubic suspension, most data related to comparisons of anterior repair with
      Burch colposuspension. The few data describing comparison of anterior repair with
      the Marshall-Marchetti-Krantz procedure were consistent with those for Burch
      colposuspension. REVIEWER'S CONCLUSIONS: There were not enough data to allow
      comparison of anterior vaginal repair with physical therapy or needle suspension
      for primary urinary stress incontinence in women. Open abdominal retropubic
      suspension appeared to be better than anterior vaginal repair judged on
      subjective cure rates in six trials, even in women who had prolapse in addition
      to stress incontinence (four trials). The need for repeat incontinence surgery
      was also less after the abdominal operation. However, there was not enough
      information about post-operative complications and morbidity.

PMID- 10908511
TI  - Diuretics acting on the distal renal tubule for preterm infants with (or
      developing) chronic lung disease.
AB  - OBJECTIVES: The aim of this review is to assess the risks and benefits of
      diuretics acting on distal segments of the renal tubule (distal diuretics) in
      preterm infants with or developing chronic lung disease (CLD). Primary objectives
      are to assess changes in need for oxygen or ventilatory support and effects on
      long-term outcome, and secondary objectives are to assess changes in pulmonary
      mechanics and potential complications of therapy. SEARCH STRATEGY: We used the
      standard method of the Cochrane Neonatal Review Group. We used the following
      keywords: ?<bronchopulmonary dysplasia> or <chronic lung disease>? and <explode
      diuretics>, limited to <human> and limited to <infant, newborn> or <infant>. We
      searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled
      Trials Register (CCTR) from the Cochrane Library (1999, issue 2). In addition, we
      hand searched several abstract books of national and international American and
      European Societies. SELECTION CRITERIA: We included in this analysis trials in
      which preterm infants with or developing CLD and at least five days of age were
      all randomly allocated to receive a distal diuretic (i.e., a diuretic acting on
      the distal renal tubule). Eligible studies needed to assess at least one of the
      outcome variables defined a priori for this systematic review. Primary outcome
      variables included changes in need for respiratory support and oxygen
      supplementation, mortality, bronchopulmonary dysplasia (BPD), death or BPD,
      chronic lung disease at 36 weeks of postconceptional age (gestational age +
      postnatal age), length of stay, and number of rehospitalizations during the first
      year of life. Secondary outcome variables included pulmonary mechanics and
      potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the
      standard method for the Cochrane Collaboration which is described in the Cochrane
      Collaboration Handbook. Two investigators extracted, assessed and coded
      separately all data for each study, using a form that was designed specifically
      for this review. Any disagreement was resolved by discussion. We combined
      parallel and cross-over trials and, whenever possible, transformed baseline and
      final outcome data measured on a continuous scale into change scores using
      Follmann's formula. MAIN RESULTS: Of six studies fulfilling entry criteria, most
      focused on pathophysiological parameters and did not assess effects on important
      clinical outcomes defined in this review, or the potential complications of
      diuretic therapy. In preterm infants > 3 weeks of age with CLD, a four-week
      treatment with thiazide and spironolactone improved lung compliance and reduced
      the need for furosemide. Thiazide and spironolactone decreased the risk of death
      and tended to decrease the risk for lack of extubation after 8 weeks in intubated
      infants who did not have access to corticosteroids, bronchodilators or
      aminophylline. However, there is little or no evidence to support any benefit of
      diuretic administration on need for ventilatory support, length of hospital stay,
      or long-term outcome in patients receiving current therapy. There is no evidence
      to support the hypothesis that adding spironolactone to thiazide or that adding
      metolazone to furosemide improves the outcome of preterm infants with CLD.
      REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and
      chronic administration of distal diuretics improve pulmonary mechanics. Studies
      are needed to assess (1) whether thiazide administration improves mortality,
      duration of oxygen dependency, ventilator dependency, length of hospital stay and
      long-term outcome in patients exposed to corticosteroids and bronchodilators (2)
      whether adding spironolactone to thiazides or adding metolazone to furosemide has
      any beneficial effect.

PMID- 10908512
TI  - Lumbar supports for prevention and treatment of low back pain.
AB  - BACKGROUND: Lumbar supports are used in the treatment of low back pain patients
      to make the impairment and disability vanish or decrease. Lumbar supports are
      also used to prevent the onset of low back pain (primary prevention) or to
      prevent recurrences of a low back pain episode (secondary prevention).
      OBJECTIVES: The objective of this systematic review was to assess the effects of
      lumbar supports for prevention and treatment of non-specific low back pain.
      SEARCH STRATEGY: We searched the Medline, Cinahl and Current Contents databases
      and the Cochrane Controlled Trials Register up to September 1999, and the Embase
      database up to September 1998. We also screened references given in relevant
      reviews and identified controlled trials, and used Science Citation Index to
      identify additional controlled trials. SELECTION CRITERIA: Controlled clinical
      trials that reported on any type of lumbar supports as preventive or therapeutic
      intervention for non-specific low back pain were included. DATA COLLECTION AND
      ANALYSIS: One reviewer extracted data from the trials considering characteristics
      of the study population, characteristics of the interventions and the final
      results for each outcome measure. The reviewer compared these findings to data
      regarding the same characteristics of the same studies published already in other
      reviews. The methodological quality was independently assessed by two reviewers.
      Because it was not possible to perform a quantitative analysis, a qualitative
      meta-analysis was performed in which the strength of evidence on the
      effectiveness of lumbar supports was classified as being strong, moderate,
      limited or conflicting, and no evidence. MAIN RESULTS: Five randomized and two
      nonrandomized controlled preventive trials and six randomized therapeutic trials
      were included in our review. Overall the methodological quality of the studies
      included in our review was rather low. Only four of the thirteen studies scored
      positive on 50% or more of the the internal validity items. There was moderate
      evidence that for primary prevention lumbar supports are not more effective than
      other types of treatment or no intervention. No evidence was found on the
      effectiveness of lumbar supports for secondary prevention. The systematic review
      of therapeutic trials showed that there is limited evidence that lumbar supports
      are more effective than no treatment, while it is still unclear if lumbar
      supports are more effective than other interventions for treatment of low back
      pain. REVIEWER'S CONCLUSIONS: There is still a need for high quality randomised
      trials on the effectiveness of lumbar supports. One of the most essential issues
      to tackle in these future trials seems to be the realisation of an adequate
      compliance.

PMID- 10908513
TI  - Opioid antagonists for alcohol dependence.
AB  - BACKGROUND: The benefits of selective serotonin reuptake inhibitors, disulfiram,
      and lithium have not been clear for people with alcohol dependence. While the
      results of many studies have suggested that opioid agonists increase alcohol
      consumption, others have shown that mu-opioid antagonists and partial agonists
      reduce alcohol consumption. The results from animal studies suggest that these
      agents may prevent the reinforcing effects of alcohol consumption. Based on the
      results of those animal studies, some opioid antagonists, such as, naltrexone,
      nalmefene, have been studied for their benefits in treating alcohol dependence.
      OBJECTIVES: To determine the effectiveness of opioid antagonists in attenuating
      or preventing the recommencement of alcohol consumption in patients with alcohol
      dependence in comparison to placebo, other medications and psychosocial
      treatments. In addition, discontinuation rate, death, patient satisfaction,
      functioning, health-related quality of life and economic outcomes were also
      evaluated. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE, CINAHL and
      Cochrane Controlled Trials Register were undertaken. Du Pont Pharmaceutical and
      Ivax Corporation were contacted for information regarding unpublished trials. The
      reference lists of the obtained papers were also examined. SELECTION CRITERIA:
      All relevant randomised controlled trials (RCTs) and clinical control trials
      (CCTs) were included. Participants were people with alcohol dependence, diagnosed
      by any set of criteria, except alcohol dependence who were currently abstinent.
      Naltrexone (NTX), nalmefene (NMF) and other opioid antagonists with/without other
      biological or psychosocial treatments were examined. A variety of clinical
      outcomes, for example alcohol consumption, duration of abstinence, were
      considered. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated and extracted
      the data independently. The dichotomous data were extracted on an intention-to
      treat basis in which the dropouts were assigned as participants with the worst
      outcomes. The Peto Odds Ratio with the 95% confidence interval was used to assess
      the dichotomous data. Weighted Mean Difference with 95% confidence interval was
      used to assess the continuous data. MAIN RESULTS: The short-term (< 3 months)
      benefits of NTX were shown in three respects, which were number of patients who
      return to drinking, percentage or number of drinking days and the number of
      standard drinks of alcohol. However, 6 months after the completion of 12-week NTX
      treatment, the benefit of decreasing the number of patients who return to
      drinking were lost. The short-term evidence from a small sample-size study
      suggested that disulfiram was more effective than NTX in the respects of number
      of abstinent days, percentage or number of drinking days and number of standard
      drinks of alcohol. The evidence from another small sample-size study also
      suggested that NTX plus an aversive agent was superior to an aversive agent alone
      in the respect of number of patients who return to drinking in short-, medium-,
      and long-term treatment. From two short-term and small sample-size studies, the
      benefit of NMF was shown only in the respect of number of patients who return to
      drinking. REVIEWER'S CONCLUSIONS: Due to the limited evidence, the following
      conclusions should be viewed as tentative. NTX has some benefits for patients
      with alcohol dependence, but patients' adherence to treatment should be of
      concern. Psychosocial treatments should be concurrently given with NTX. The
      optimal duration of NTX treatment is not yet known. Although NTX is available for
      treating alcohol dependence in many countries, in the respect of cost
      effectiveness, disulfiram should still remain as an alternative. Due to the
      dearth of evidence, at present, the combination of NTX and disulfiram or NMF
      alone should not be used in everyday clinical practice. Randomised, double-blind,
      placebo-controlled trials of NTX treatment in patients with alcohol dependence

PMID- 10908514
TI  - Lamotrigine add-on for drug-resistant partial epilepsy.
AB  - BACKGROUND: Epilepsy is a common neurological disorder, affecting almost 0.5 to
      1% of the population. Nearly 30% of patients with epilepsy are refractory to
      currently available drugs. Lamotrigine is one of the newer antiepileptic drugs
      and is the topic of this review. OBJECTIVES: To examine the effects of
      lamotrigine on seizures, side effects, cognition and quality of life, when used
      as an add-on treatment for patients with drug-resistant partial epilepsy. SEARCH
      STRATEGY: We searched the Cochrane Epilepsy Group trials register, the Cochrane
      Controlled Trials Register (Cochrane Library Issue 1, 2000), MEDLINE (January
      1966 to December 1999) and reference lists of articles. We also contacted the
      manufacturers of lamotrigine (Glaxo-Wellcome). SELECTION CRITERIA: Randomized
      placebo controlled trials, of patients with drug-resistant partial epilepsy of
      any age, in which an adequate method of concealment of randomization was used.
      The studies may be double, single or unblinded. For crossover studies, the first
      treatment period was treated as a parallel trial. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently assessed the trials for inclusion and extracted data.
      Primary analyses were by intention to treat. Outcomes included 50% or greater
      reduction in seizure frequency, treatment withdrawal (any reason), side effects,
      effects on cognition, and quality of life. MAIN RESULTS: We found three parallel
      add-on studies and eight cross-over studies, which included 1243 patients (199
      children and 1044 adults). The overall Peto's Odds Ratio (OR) and 95% confidence
      intervals (CIs) across all studies for 50% or greater reduction in seizure
      frequency was 2.71 (1.87, 3.91) indicating that lamotrigine is significantly more
      effective than placebo in reducing seizure frequency. The overall OR (95%CI) for
      treatment withdrawal (for any reason) is 1.12 (0.78, 1. 61). The 99% CIs for
      ataxia, dizziness, nausea, and diplopia do not include unity, indicating that
      they are significantly associated with lamotrigine. The limited data available
      preclude any conclusions about effects on cognition and quality of life, though
      there may be minor benefits in affect balance (happiness) and mastery. REVIEWER'S
      CONCLUSIONS: Lamotrigine add-on therapy is effective in reducing the seizure
      frequency, in patients with drug-resistant partial epilepsy. Further trials are
      needed to assess the long term effects of lamotrigine, and to compare it with
      other add-on drugs.

PMID- 10908515
TI  - Oral protein calorie supplementation for children with chronic disease.
AB  - BACKGROUND: Growth failure and poor nutritional status are common features in
      children with chronic diseases due to reduced appetite, malabsorption and
      increased nutritional requirements associated with some diseases. The provision
      of oral protein calorie supplements is one of a number of interventions used to
      improve nutritional status in these children. The use of these products, which
      are expensive, may be associated with a number of adverse effects, for example,
      they may effect development of normal eating behaviour patterns or lead to
      unpleasant symptoms such as vomiting and diarrhoea. OBJECTIVES: To examine the
      evidence that in children with chronic disease, oral protein calorie supplements
      alter daily nutrient intake, nutritional indices, survival and quality of life
      and are associated with adverse effects, for example diarrhoea, vomiting, reduced
      appetite, glucose intolerance, bloating and eating behaviour problems. SEARCH
      STRATEGY: All publications describing RCTs of the use of oral protein calorie
      supplements in children with chronic diseases were identified through
      comprehensive electronic database searches, handsearching relevant journals and
      handsearching abstract books of conference proceedings. The companies which
      market oral protein calorie supplements were also contacted. SELECTION CRITERIA:
      All randomised or quasi-randomised controlled trials comparing use of oral
      protein calorie supplements for at least one month to increase calorie intake
      with existing conventional therapy, which may include nutritional advice on how
      to improve nutritional intake from food or no specific intervention, in children
      with chronic disease. DATA COLLECTION AND ANALYSIS: The following outcomes were
      assessed: indices of nutrition and growth, anthropometric measures of body
      composition, calorie and nutrient intake (total, from oral protein calorie
      supplements and from food), eating behaviour, compliance, quality of life,
      specific adverse effects and disease severity scores, and mortality. MAIN
      RESULTS: Three trials have been identified as being suitable for inclusion in the
      review and we are awaiting further data from one of these trials. All of these
      trials were carried out in children with cystic fibrosis. Few statistical
      differences could be found between the treatment and control groups apart from
      change in total fat intake at three months (weighted mean difference 69.20 [95%
      CI 11.05, 127.35]). However, this was based on the results of only one, small
      study. No trials have been identified which assess the effectiveness of oral
      protein calorie supplements in children with other chronic diseases. REVIEWER'S
      CONCLUSIONS: Oral protein calorie supplements are widely used to improve the
      nutritional status of children with a number of chronic diseases. We have only
      been able to identify a small number of trials assessing these products in
      children with cystic fibrosis and have been unable to draw any conclusions based
      on the limited data extracted from these. We therefore recommend that a series of
      large, randomised controlled trials are undertaken investigating the use of these
      products in children with different chronic diseases. Until further data are
      available, we would suggest that these products are only used with caution.

PMID- 10908516
TI  - Psychological therapies for sickle cell disease and pain.
AB  - BACKGROUND: Sickle cell disease comprises of a group of genetic blood disorders,
      and occurs when the sickle cell haemoglobin gene is inherited from both parents.
      The effects of the condition are: varying degrees of anaemia which if severe
      reduce the capacity for mobility; predisposition to obstruction of small blood
      capillaries causing pain in muscle and bone known as "crises"; damage to major
      organs such as the spleen, liver, kidneys, and lungs; and increased vulnerability
      to severe infections. There are both medical and non-medical complications, and
      treatment is usually symptomatic and palliative in nature. Psychological
      intervention for individuals with sickle cell disease seems viable in
      complementing current medical treatment, and studies examining their efficacy
      appear to have also yielded encouraging results. OBJECTIVES: To examine the
      evidence that in patients with sickle cell disease, psychological treatment
      improves the ability to cope with the condition. SEARCH STRATEGY: The Cochrane
      Cystic Fibrosis and Genetic Disorders Group specialist trials register which
      comprises references from comprehensive electronic database searches,
      handsearching relevant journals and handsearching abstract books of conference
      proceedings. Also, searches on the Internet were performed. SELECTION CRITERIA:
      All randomised or quasi-randomised controlled trials comparing the use of
      psychological intervention to no (psychological) intervention in patients with
      sickle cell disease. DATA COLLECTION AND ANALYSIS: The following outcomes were
      assessed: pain, mood, coping, health service utilisation, general health, quality
      of life, and life satisfaction. MAIN RESULTS: Four trials which reported results
      were all found to be unsuitable for inclusion at the present time, owing to
      incomplete data in the published papers. REVIEWER'S CONCLUSIONS: Psychological
      approaches are commonly used in an attempt to improve coping ability in patients
      with sickle cell disease. No conclusions can be made about the use of specific
      psychological therapies in sickle cell disease from the information currently
      available. This systematic review has clearly identified the need for well
      designed, adequately-powered, multicentre, RCTs assessing the effectiveness of
      specific interventions in sickle cell disease.

PMID- 10908517
TI  - Thioridazine for schizophrenia.
AB  - BACKGROUND: Thioridazine is a piperidine phenothiazine used for the treatment of
      people with schizophrenia. It has often been considered the drug of choice in the
      elderly because of reputed lower levels of extrapyramidal adverse events. It may,
      however, be more likely to cause cognitive adverse events, such as delirium or
      worsening of memory, and, on rare occasions, thioridazine has caused pigmentary
      retinopathy. OBJECTIVES: To examine the effects of thioridazine for those with
      schizophrenia, and, in particular, elderly people with schizophrenia. SEARCH
      STRATEGY: Electronic searches of Biological Abstracts (1980-1999), CINAHL (1982
      1999), The Cochrane Library (Issue 3, 1999), The Cochrane Schizophrenia Group's
      Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974
      1999) and Sociofile (1974-1999) were undertaken. References of all identified
      studies were searched for further trials. Pharmaceutical companies and authors of
      trials were contacted. SELECTION CRITERIA: All randomised clinical trials that
      compared thioridazine to other treatments for people with schizophrenia or other
      psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts
      were independently inspected by reviewers, papers ordered, re-inspected and
      quality assessed. Data were independently extracted. Data were excluded if loss
      to follow up was greater than 40%. For homogeneous dichotomous data the Relative
      Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed
      to treat (NNT) were calculated on an intention-to-treat basis. For continuous
      data, weighted mean differences were calculated (WMD). All data were inspected
      for heterogeneity. MAIN RESULTS: 560 people from 11 studies were randomised to
      thioridazine or placebo. For change in global state, small, short term studies
      (three months or less) found no difference between groups (RR 0.66 CI 0.35-1.23,
      n=100). At six months, however, two small studies (n=65) favoured thioridazine
      (RR 0.34 CI 0.21-0. 56, NNT 2 CI 1-6). Fourteen percent in the thioridazine group
      left early compared to 32% of people allocated to placebo (RR 0.43 CI 0. 31-0.61,
      NNT 6 CI 4-10, n=510). Few differences in terms of adverse effects, between
      thioridazine and placebo, were apparent. Limited data from trials suggest that
      thioridazine is not strongly anticholinergic (blurred vision RR 2.01 CI 0.56
      7.25, n=224). Thioridazine is not sedating (at three months to one year RR 2.48
      CI 0.96-6.4, n=122). No data were presented on retinal changes. Two thousand
      three hundred ninety-seven patients from 26 studies were randomised to
      thioridazine versus typical antipsychotics. For the outcome 'no better or worse',
      those allocated to thioridazine were no better off than people given control
      typical neuroleptics (RR 0. 97 CI 0.78-1.21, n=771). There were no clear
      differences between thioridazine and other drugs for the outcome 'Mental state -
      no better or worse' on the BPRS by three months (RR 1.3 CI 0.8-2.11, n=208).
      Twenty-one studies (n=1737) had 19% attrition in both groups. Few differences
      were seen in the lists of adverse effects. As expected from the placebo
      comparison, thioridazine does not cause more anticholinergic-type symptoms than
      other drugs. About half of people given thioridazine felt drowsy or sedated but
      this was no different from other drugs (RR 1.06 CI 0.93-1.2, n=909). Parkinsonism
      was less common in the thioridazine group in the short term (RR 0.29 CI 0.12-0.7,
      n=340). One small study (n=40) found no clear differences between thioridazine
      and clozapine. REVIEWER'S CONCLUSIONS: Although there are shortcomings and gaps
      in the data, there appears to be enough consistency over different outcomes and
      periods to confirm that thioridazine is an antipsychotic of similar efficacy to
      other commonly used neuroleptics for people with schizophrenia. Its adverse
      events profile is similar to that of other drugs, but it may have a lower level
      of extrapyramidal problems. (ABSTRACT TRU

PMID- 10908518
TI  - Pimozide for schizophrenia or related psychoses.
AB  - BACKGROUND: Pimozide was first formulated in the late 1960s and continues to be
      marketed for the care of those with schizophrenia or related psychoses such as
      delusional disorder. Pimozide is generally well tolerated apart from
      extrapyramidal side effects. It has, however, been associated with cardiotoxicity
      and sudden unexplained deaths and electrocardiogram monitoring is now required
      before and during its use. OBJECTIVES: To assess the effects of pimozide for
      people with schizophrenia, non-affective psychotic mental illness and delusional
      disorder in terms of clinical, social and economic outcomes. SEARCH STRATEGY:
      Electronic searches of Biological Abstracts (1982-1995), The Cochrane
      Schizophrenia Group's Register, EMBASE (1980-1995), Janssen-Cilag UK's register
      of studies (1999), MEDLINE (1966-1995), PsycLIT (1974-1995), hand-searching the
      references of all included studies and contacting the manufacturers of the
      compound. SELECTION CRITERIA: All randomised trials relating to people with
      schizophrenia, or similar disorders comparing pimozide to other drug treatments
      were sought. Studies where randomisation was implied rather than stated were
      included if they did not change the results. Primary outcomes were clinically
      significant change in global function, mental state, relapse, hospital admission,
      death, adverse events and acceptability of treatment. DATA COLLECTION AND
      ANALYSIS: Studies were selected, rated and data extracted. For dichotomous data
      Relative Risks (RR) based on a random effects model with 95% confidence intervals
      (CI) were estimated. The number needed to treat statistic (NNT) was calculated
      where indicated. Analysis was by intention-to-treat. MAIN RESULTS: This review
      currently includes 34 studies focusing on those with schizophrenia, none on
      people with delusional disorder. Few people have been randomised to pimozide
      versus placebo. Data from two longer term studies does suggest that the active
      drug prevents relapse (n=66, RR 0.45 CI 0.24-0.86, NNT 4, CI 3-22) but the
      confidence interval is wide. Pimozide has similar efficacy to that of typical
      antipsychotic drugs for the outcomes of change in global functioning, mental
      state, relapse and leaving the study early. People allocated to pimozide did not
      have a higher mortality than those taking other antipsychotics. Pimozide was more
      likely to cause parkinsonian tremor (RR 1.6 CI 1.1-2.3, NNH 6 CI 3-44) and lead
      to a requirement for antiparkinsonian medication more frequently (RR 1.8, CI 1.2
      2.6, NNH 3 CI 2-5) than other drugs. It was, however, less likely to cause
      sedation (RR 0.38 CI 0.2-0.7, NNH 6 CI 4-16). REVIEWER'S CONCLUSIONS: Although
      there are shortcomings in the data there is enough overall consistency, over
      different outcomes and time scales, to confirm that pimozide is a drug with
      similar efficacy to other more commonly used antipsychotics such as
      chlorpromazine for those with schizophrenia. There are no data to support or
      refute its use for those with delusional disorder.

PMID- 10908519
TI  - Prophylactic doxapram for the prevention of morbidity and mortality in preterm
      infants undergoing endotracheal extubation.
AB  - BACKGROUND: When preterm infants have been given intermittent positive pressure
      ventilation (IPPV) for respiratory failure, weaning from support and tracheal
      extubation may be difficult. A significant contributing factor is thought to be
      the relatively poor respiratory effort and tendency to develop hypoventilation
      and apnea, particularly in very preterm infants. Doxapram stimulates breathing
      and appears to act via stimulation of both the peripheral chemoreceptors and the
      central nervous system. This effect might increase the chance of successful
      tracheal extubation. OBJECTIVES: In preterm infants being weaned from IPPV and in
      whom endotracheal extubation is planned, does treatment with doxapram reduce the
      use of intubation and IPPV, or reduce other morbidity, without clinically
      important side effects? In this regard, how does doxapram compare with standard
      treatment or with an alternative treatment such as methylxanthine or CPAP?
      Subgroup analyses were prespecified according to birth weight and/or gestational
      age, use of co-interventions (methylxanthines or nasal CPAP), and route of
      administration (intravenous or oral). SEARCH STRATEGY: The standard search
      strategy of the Neonatal Review Group as outlined in the Cochrane Library was
      used. This included searches of the Oxford Database of Perinatal Trials, Cochrane
      Controlled Trials Register, MEDLINE and EMBASE. SELECTION CRITERIA: Eligible
      studies included published trials utilising random or quasi-random patient
      allocation in which preterm or low birth weight infants being weaned from IPPV
      were given doxapram compared with standard care or other treatments, to
      facilitate weaning from IPPV and endotracheal extubation. Trials were
      independently assessed by the authors before inclusion. DATA COLLECTION AND
      ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal
      Review Group were used. Each author extracted data separately; the results were
      compared and any differences resolved. The data were synthesized using the
      standard method of Neonatal Review Group with use of relative risk and risk
      difference. MAIN RESULTS: Two trials involving a total of 85 infants compared
      doxapram and placebo. In both the individual trials and the meta-analyses there
      were no significant differences between the doxapram and placebo groups in any of
      the outcomes (failed extubation, death before discharge, respiratory failure,
      duration of IPPV, side effects, oxygen at 28 days or oxygen at discharge). There
      was a trend towards an increase in side effects (hypertension or irritability
      leading to cessation of treatment) in the doxapram group [summary RR 3.21 (0.53,
      19.43). In one of these two trials (Huon 1998) an 'alarming rise in blood
      pressure' occurred in five infants in the doxapram group and none of the
      controls, although in only one was treatment withdrawn. One additional trial
      involving only eight infants compared doxapram with aminophylline, but there were
      insufficient data for meaningful analysis. REVIEWER'S CONCLUSIONS: The evidence
      does not support the routine use of doxapram to assist endotracheal extubation in
      preterm infants who are eligible for methylxanthine and/or CPAP. The results
      should be interpreted with caution because the small number of infants studied
      does not allow reliable assessment of the benefits and harms of doxapram. Further
      trials are required to evaluate the benefits and harms of doxapram compared with
      no treatment or with other treatments, such as methylxanthines or CPAP, to
      evaluate whether it is more effective in infants not responding to these other
      treatments, and to assess whether the drug is effective when given orally.

PMID- 10908520
TI  - Bypass surgery for chronic lower limb ischaemia.
AB  - BACKGROUND: Surgical bypass of an occluded arterial segment is the mainstay of
      treatment for patients with critical limb ischaemia. As with many surgical
      interventions, however, it was introduced without formal evaluation. OBJECTIVES:
      The objective of this review was to determine the effects of bypass surgery in
      patients with chronic lower limb ischaemia. SEARCH STRATEGY: The reviewers
      searched the Cochrane Peripheral Vascular Diseases Group trials register,
      MEDLINE, EMBASE, reference lists of relevant articles, and contacted principal
      trial investigators. SELECTION CRITERIA: All randomised controlled trials of
      bypass surgery versus control, or versus any other form of treatment. DATA
      COLLECTION AND ANALYSIS: At least two reviewers extracted data and assessed trial
      quality independently. The reviewers contacted investigators to obtain
      information or data needed for the review that could not be found in published
      reports. Dichotomous data were analysed using the Peto odds ratio (OR), and
      continuous data with the weighted mean difference (fixed effect and random
      effects models). MAIN RESULTS: Eight trials were identified which appeared to
      meet the inclusion criteria, but two were subsequently excluded. The remaining
      six trials involved a total of just over 700 patients, two trials comparing
      bypass surgery with angioplasty (PTA), and one with each of
      thromboendarterectomy, thrombolysis, exercise, and spinal cord stimulation. Four
      trials included patients with a range of disease severity (intermittent
      claudication and critical limb ischaemia), one was restricted to claudicants only
      and another to only critical limb ischaemia. The type of bypass procedure
      performed in each trial was similar: vein grafts for distal reconstructions;
      synthetic prostheses for aorto-iliac or ilio-femoral bypasses. The outcome
      measures varied, but four of the six trials included mortality and operative
      failure. In general the quality of the trials was good, but none was blinded
      because of the nature of the intervention. There were no clear differences
      between bypass surgery and PTA. Mortality and amputation rates did not differ
      significantly, although primary patency was significantly higher in the bypass
      group after 12 months (Peto OR 1. 6, 95% CI 1.0, 2.6) but not after four years
      (p=0.14). Compared with thrombolysis, amputation rates were significantly lower
      in the bypass group (Peto OR 0.2, 95% CI 0.1, 0.6), but mortality rates did not
      differ. Compared with thromboendarterectomy, restoration of blood flow was
      significantly greater in the bypass patients (Peto OR 9.2, 95% CI 1.7, 50.6), but
      mortality and amputation rates did not differ. Bypass did not differ
      significantly from exercise or spinal cord stimulation. REVIEWER'S CONCLUSIONS:
      There is limited evidence for the effectiveness of bypass surgery and further
      large trials are required.

PMID- 10908521
TI  - Buprenorphine for the management of opioid withdrawal.
AB  - BACKGROUND: Managed withdrawal, or detoxification, is not in itself a treatment
      for opioid dependence, but it is a required first step for many forms of longer
      term treatment. It may also represent the end point of an extensive period of
      treatment such as methadone maintenance. As such, managed withdrawal is an
      essential component of an effective treatment system. This review is one of a
      series that aims to assess the evidence as to the effectiveness of the variety of
      approaches to managing opioid withdrawal. OBJECTIVES: To assess the effectiveness
      of interventions involving the short-term use of buprenorphine to manage the
      acute phase of opioid withdrawal. SEARCH STRATEGY: Multiple electronic databases,
      including Medline, Embase, Psychlit, Australian Medical Index and Current
      Contents, were searched using a strategy designed to retrieve references broadly
      addressing the management of opioid withdrawal. Reference lists of retrieved
      studies, reviews and conference abstracts were handsearched. SELECTION CRITERIA:
      We included randomised or quasi-randomised controlled clinical trials or
      prospective controlled cohort studies comparing buprenorphine (treatment 10 days
      or less) with another form of treatment. Studies were required to provide
      detailed information on the type and dose of drugs used and the characteristics
      of patients treated. Studies were also required to provide information on the
      nature of withdrawal signs and symptoms experienced, the occurrence of adverse
      effects OR rates of completion of the withdrawal episode. DATA COLLECTION AND
      ANALYSIS: Potentially relevant studies were assessed for inclusion by one
      reviewer (LG). Inclusion decisions were confirmed by consultation between
      reviewers. Included studies were assessed by all reviewers. One reviewer (LG)
      undertook data extraction with the process confirmed by consultation between all
      three reviewers. MAIN RESULTS: Five studies met the criteria for inclusion in the
      review. No data tables are included in this review and no meta-analysis has been
      undertaken because of differences in treatment regimes and the assessment of
      outcomes in these studies. Four studies compared buprenorphine with clonidine.
      All found withdrawal to be less severe in the buprenorphine treatment group. In
      three of these studies all participants were withdrawing from heroin.
      Participants in one study were withdrawing from methadone, with doses reduced to
      10mg/day prior to treatment with buprenorphine. Three of the studies commented on
      residual symptoms experienced by participants treated with buprenorphine to
      manage heroin withdrawal. Aches, restlessness, yawning, mydriasis, tremor,
      insomnia, nausea and mild anxiety were reported as being experienced by some
      participants. Rates of completion of withdrawal were able to be calculated for
      all studies included in the review but the definition of completion varied
      between studies. Rates ranged from 65% to 100%. None of the studies included in
      the review reported adverse effects. However, approximately approximately
      Lintzeris 1999a approximately approximately (a single-group study which therefore
      did not meet the inclusion criteria) reported 50% of participants withdrawing
      from heroin experienced headaches, 28% sedation, 21% nausea, 21% constipation,
      21% anxiety, 17% dizziness and 17% itchiness during withdrawal. These adverse
      effects were most common in the first 2-3 days of treatment and then subsided. In
      four of the five studies treatment was undertaken on an inpatient basis. Only
      approximately approximately O'Connor 1997 approximately approximately provided
      outpatient treatment. However, two studies that did not meet the inclusion
      criteria ( approximately approximately Diamant 1998 approximately approximately
      and approximately approximately Lintzeris 1999a approximately approximately )
      also provided outpatient treatment. The findings of these studies support the
      feasibility of heroin withdrawal being managed with buprenorphine on an
      outpatient basis

PMID- 10908522
TI  - Oxcarbazepine add-on for drug-resistant partial epilepsy.
AB  - BACKGROUND: Most people with epilepsy have a good prognosis and their seizures
      can be well controlled with the use of a single antiepileptic drug, but up to 30
      % develop refractory epilepsy, especially those with partial seizures. In this
      review we summarise the current evidence regarding oxcarbazepine when used as an
      add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the
      effects of oxcarbazepine when used as an add-on treatment for drug-resistant
      partial epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's
      trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue
      1, 2000), MEDLINE (January 1966 to December 1999) and reference lists of
      articles. We also contacted Novartis (manufacturers of oxcarbazepine) and experts
      in the field. SELECTION CRITERIA: Randomized, placebo-controlled, double-blind,
      add-on trials of oxcarbazepine in patients with drug-resistant partial epilepsy.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for
      inclusion and extracted the relevant data. The following outcomes were assessed :
      (a) 50 % or greater reduction in seizure frequency; (b) treatment withdrawal (any
      reason); (c) side effects. Primary analyses were intention to treat. Summary odds
      ratios were estimated for each outcome. MAIN RESULTS: Overall Odds Ratio (OR) (95
      % Confidence Interval (CIs)) for 50 % or greater reduction in seizure frequency
      compared to placebo 2.96 (2.20,4.00). Treatment withdrawal OR (95 % CIs) compared
      to placebo 2.17 (1.59,2.97). Side effects: OR (99 % CIs) compared to placebo,
      ataxia 2.93(1.72,4.99); dizziness 3.05 (1.99, 4. 67); fatigue 1.80 (1.02, 3.19);
      nausea 2.88 (1.77, 4.69); somnolence 2.55 (1.84, 3.55); diplopia 4.32 (2.65,
      7.04), were significantly associated with oxcarbazepine. REVIEWERS' CONCLUSIONS:
      Oxcarbazepine has efficacy as an add-on treatment in patients with drug-resistant
      partial epilepsy, both in adults and children. However, trials reviewed were of
      relatively short duration, and provide no evidence about the long term effects of
      oxcarbazepine. Results cannot be extrapolated to monotherapy or to patients with
      other epilepsy types.

PMID- 10908523
TI  - Zidovudine (AZT) versus AZT plus didanosine (ddI) versus AZT plus zalcitabine
      (ddC) in HIV infected adults.
AB  - BACKGROUND: Zidovudine (AZT) monotherapy was the first antiretroviral drug to be
      tested widely. The next two drugs to be developed were didanosine (ddI) and
      zalcitabine (ddC). OBJECTIVES: To assess the effects of zidovudine (AZT),
      zidovudine plus didanosine (ddI) and zidovudine plus zalcitabine (ddC) on HIV
      disease progression and survival. SEARCH STRATEGY: Investigators and
      pharmaceutical companies were contacted, and MEDLINE searches were supplemented
      by searching conference abstracts. SELECTION CRITERIA: Randomised controlled
      trials comparing any two of AZT plus ddI, AZT plus ddC or AZT alone in
      participants with or without AIDS which collected information on deaths and new
      AIDS events. DATA COLLECTION AND ANALYSIS: Individual patient data with, wherever
      possible, follow-up obtained beyond that previously published were obtained and
      checked for internal consistency and consistency with any published reports; any
      apparent discrepancies were resolved with the trialists. Time to death and to
      disease progression (defined as a new AIDS-defining event or prior death) were
      analysed on an intention to treat basis, stratified to avoid direct comparisons
      between participants in different trials. MAIN RESULTS: Six trials were included
      in the meta-analysis. During a median follow-up of 29 months, 2904 individuals
      progressed, of whom 1850 died. The addition of ddI to AZT delayed both
      progression (RR 0.74; 95% CI 0.67 to 0.82, P<0.0001) and death (RR 0.72; 95% CI
      0.64 to 0.82, P<0.0001). Likewise, the addition of ddC to AZT also delayed
      progression (RR 0. 86; 95% CI 0.78 to 0.94, P=0.001) and death (RR 0.87; 95% CI
      0.77 to 0.98, P=0.02). After 3 years the estimated percentages alive and without
      a new AIDS event were 53% for AZT+ddI, 49% for AZT+ddC and 44% for AZT alone; the
      percentages alive were 68%, 63% and 59% respectively. Five of the six trials
      involved randomised comparisons of AZT+ddI versus AZT+ddC: in these, the AZT+ddI
      regimen had greater effects on disease progression (P=0.004) and death (P=0.009).
      REVIEWER'S CONCLUSIONS: The use of ddI and, to a lesser extent, ddC delayed both
      HIV disease progression and death, at least when added to AZT.

PMID- 10908524
TI  - Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic
      HIV infected adults.
AB  - BACKGROUND: Zidovudine (AZT) monotherapy was the first antiretroviral drug to be
      tested widely. Subsequent trials in asymptomatic or early symptomatic HIV
      infection indicated short-term delays in disease progression with AZT, but not
      improved survival. OBJECTIVES: To assess the effects of immediate versus deferred
      zidovudine (AZT) on HIV disease progression and survival. SEARCH STRATEGY:
      Investigators and pharmaceutical companies were contacted, and MEDLINE searches
      were supplemented by searching conference abstracts. SELECTION CRITERIA:
      Randomised controlled trials comparing immediate versus deferred AZT in
      participants without AIDS which prospectively collected deaths and new AIDS
      events. DATA COLLECTION AND ANALYSIS: Individual patient data with, wherever
      possible, follow-up obtained beyond that previously published was obtained and
      checked for internal consistency and consistency with any published reports; any
      apparent discrepancies were resolved with the trialists. Time to death and to
      disease progression (defined as a new AIDS-defining event or prior death) were
      analysed on an intention to treat basis, stratified to avoid direct comparisons
      between participants in different trials. MAIN RESULTS: Nine trials were included
      in the meta-analysis. During a median follow-up of 50 months, 1908 individuals
      developed disease progression, of whom 1351 died. In the deferred group, 61%
      started antiretroviral therapy (median time to therapy 28 months, which was AZT
      monotherapy in 94%). During the first year of follow-up immediate AZT halved the
      rate of disease progression (P<0.0001), increasing the probability of AIDS-free
      survival at one year from 96% to 98%, but this early benefit did not persist:
      after 6 years AIDS-free survival was 54% in both groups, and at no time was there
      any difference in overall survival, which at 6 years was 64% with immediate and
      65% with deferred AZT (rate ratio [RR] 1.04, 95% confidence interval [CI] 0. 94
      to 1.15). REVIEWER'S CONCLUSIONS: Although immediate use of AZT halved disease
      progression during the first year, this effect was not sustained, and there was
      no improvement in survival in the short or long term.

PMID- 10908525
TI  - Tricyclic and related drugs for nocturnal enuresis in children.
AB  - BACKGROUND: Enuresis (bedwetting) is a socially unacceptable and stressful
      condition which affects around 15-20% of five year olds, and up to 2% of young
      adults. Although there is a high rate of spontaneous remission, the social,
      emotional and psychological costs to the children can be great. OBJECTIVES: To
      assess the effects of tricyclic and related drugs on nocturnal enuresis in
      children, and to compare them with other interventions. SEARCH STRATEGY: The
      following electronic databases were searched: MEDLINE to June 1997; AMED; ASSIA;
      BIDS; BIOSIS Previews (1985-1996); CINAHL; DHSS Data; EMBASE (1974 to June 1997);
      PsycLIT and SIGLE. Organisations, manufacturers, researchers and health
      professionals concerned with enuresis were contacted for information. The
      reference sections of obtained studies were also checked for further trials. Date
      of the most recent search: July 1997. SELECTION CRITERIA: All randomised trials
      of tricyclic and related drugs for nocturnal enuresis in children were included
      in the review. Trials were eligible for inclusion if: children were randomised to
      receive tricyclics compared with placebo, other drugs or other conservative
      interventions for nocturnal bedwetting; participants with organic causes for
      their bedwetting were excluded; and baseline assessments of the level of
      bedwetting were provided. Trials focused solely on daytime wetting were excluded.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the quality of
      the eligible trials, and extracted data. MAIN RESULTS: Twenty two randomised
      trials, involving 1100 children treated with tricyclic or related drugs, met the
      inclusion criteria. The quality of many of the trials was poor. Only single
      trials compared tricyclic or related drugs with each other, other drugs,
      desmopressin, alarms or other behavioural interventions. Treatment with tricyclic
      drugs (such as imipramine, amitriptyline, viloxazine, clomipramine and
      desipramine but not mianserin) were associated with a reduction of about one wet
      night per week while on treatment (eg using imipramine, WMD -0.99, 95% CI -1.27
      to -0.71). Children were almost five times more likely to achieve 14 dry nights
      with the drugs (eg using imipramine, RR = 4.99, 95% CI 2.4 to 10.40).
      Desmopressin and tricyclics appeared equally effective while on treatment, but
      this effect was not sustained after treatment stopped. There was no detectable
      difference between imipramine and alarms while on treatment, but afterwards those
      who had used alarms had one fewer wet night per week (WMD 1.03, 95% CI 0. 19 to
      1.87). REVIEWER'S CONCLUSIONS: Treatment with tricyclic drugs (imipramine,
      amitriptyline, viloxazine, clomipramine and desipramine but not mianserin) was
      associated with a reduction of about one wet night per week while on treatment,
      but long term effectiveness is unknown. Desmopressin and tricyclics appeared
      equally effective while on treatment, but this effect was not sustained after
      treatment stopped. Alarms may be more effective in the long term. Comparisons
      between drug and behavioural treatments are needed, and should include relapse
      rates after treatment is finished.

PMID- 10908526
TI  - Pharmacotherapy for hypertension in women of different races.
AB  - OBJECTIVES: To assess whether the relative and absolute benefit of hypertension
      treatment in women varies with age or race. SEARCH STRATEGY: Literature search of
      studies from 1966 to 1998 using MEDLINE, reviews, and consultation with experts.
      SELECTION CRITERIA: Studies were eligible if they were randomized controlled
      trials of pharmacological treatment of primary hypertension, with cardiovascular
      morbidity and mortality outcomes, and with over one hundred women enrolled. DATA
      COLLECTION AND ANALYSIS: The pooled population included 23,000 women. Relative
      risks were combined for each endpoint to form summary risk ratios (RR) using meta
      analytic techniques based on a random-effects model. Summary RR's were converted
      to numbers needed to treat (NNT). Data were dichotomized by age to approximate
      menopausal status (30 to 54 years, and 55 years and older), and by race (white
      and African American). MAIN RESULTS: In women ages 55 years or older (90% white),
      hypertension treatment results in a 38% risk reduction in fatal and nonfatal
      cerebrovascular events (95% confidence interval (CI) 27-47%, 5 year NNT 78), a
      25% reduction in fatal and nonfatal cardiovascular events (95% CI 17-33%, 5 year
      NNT 58), and a 17% reduction in cardiovascular mortality (95% CI 3-29%, 5 year
      NNT 282). In women ages 30 to 54 years (79% white), hypertension treatment
      results in a 41% risk reduction in fatal and nonfatal cerebrovascular events (95%
      CI 8-63%, 5 year NNT 264), and a 27% risk reduction in fatal and nonfatal
      cardiovascular events (95% CI 4-44%, 5 year NNT 259). Hypertension treatment in
      African American women (mean age 52 years) reduced the risk of fatal and nonfatal
      cerebrovascular events by 53% (95% CI 29-69%, 5 year NNT 39), fatal and nonfatal
      cardiovascular events by 45% (95% CI 18-63%, 5 year NNT 21), fatal and nonfatal
      coronary events by 33% (95% CI 6-52%, 5 year NNT 48), and all cause mortality by
      34% (95% CI 14-49%, 5 year NNT 32). Analyses in white women 30 to 54 years old
      did not show any statistically significant treatment benefit or harm. REVIEWER'S
      CONCLUSIONS: Hypertension treatment lowers the relative and absolute risk of
      cardiovascular morbidity and mortality in women ages 55 years and older, and in
      African American women of all ages. A greater effort should be made to increase
      awareness and treatment in these groups of women. Although relative risk
      reductions for cerebrovascular and cardiovascular events are similar for younger
      and older women, the NNT of younger women is at least 4 times higher. Decisions
      for treatment of hypertension in younger white women should be influenced by the
      individual patient's absolute risk of cardiovascular disease.

PMID- 10908527
TI  - Premedication for anxiety in adult day surgery.
AB  - BACKGROUND: Surgery is increasingly performed on a day-case basis. Many patients
      are anxious pre-operatively and might benefit from pharmacological anxiolysis.
      Drugs are sometimes not used, however, for fear of delaying discharge from
      hospital. OBJECTIVES: To asses the effect of anxiolytic premedication on time to
      discharge in adult patients undergoing day case surgery under general
      anaesthesia. SEARCH STRATEGY: Trials were identified by computerised searches of
      the Cochrane Controlled Trials Register, MEDLINE, EMBASE, by checking the
      reference lists of trials and review articles, by hand-searching three main
      anaesthesia journals and by contacting five researchers active in the field and
      the Product Information departments of the manufacturers of five commonly used
      premedicants. SELECTION CRITERIA: All randomised controlled trials comparing an
      anxiolytic drug(s) with placebo before general anaesthesia in adult day case
      surgical patients. DATA COLLECTION AND ANALYSIS: We collected data on anaesthetic
      drugs used, results of tests of psychomotor function where these were used to
      assess residual effect of premedication, and on times from end of anaesthesia to
      ability to walk unaided or readiness for discharge from hospital. Formal
      statistical synthesis of individual trials was not performed in view of the
      variety of drugs studied. MAIN RESULTS: Searching identified twenty-nine reports;
      fourteen studies, with data from a total of 1263 patients, were considered
      eligible for analysis. Only two studies specifically addressed the discharge
      question; both found no delay in premedicated patients. Three other studies used
      clinical criteria to assess fitness for discharge, though times were not given.
      Again, there was no difference from placebo. Four studies used both clinical
      measures and tests of psychomotor function as tests of recovery from anaesthesia.
      In none of these studies did the premedication appear to delay discharge,
      although performance on tests of psychomotor function was sometimes still
      impaired. Of the four studies which used tests of psychomotor function to assess
      recovery, three showed impaired recovery (after midazolam 7.5mg, midazolam 15mg
      or diazepam 15mg) which might possibly interfere with discharge from hospital.
      REVIEWER'S CONCLUSIONS: We have found no evidence of a difference in time to
      discharge from hospital in patients who received anxiolytic premedication.
      However, in view of the age and variety of anaesthetic techniques used,
      inferences for current day-case practice should be made with caution.

PMID- 10908528
TI  - Multidisciplinary biopsychosocial rehabilitation for subacute low back pain among
      working age adults.
AB  - BACKGROUND: Multidisciplinary biopsychosocial rehabilitation programs are widely
      applied for chronic low back pain patients. The biopsychosocial approach for low
      back pain could also be considered to prevent chronicity by carrying out the
      rehabilitation if the acute pain is prolonged. Nevertheless multidisciplinary
      treatment programmes are often laborious and long processes and require good
      collaboration between the patient, the rehabilitation team and the work place. By
      workplace visits and close relationship with occupational health care one might
      expect results in terms of patients working ability. OBJECTIVES: The objective of
      this systematic review was to determine the effectiveness of multidisciplinary
      rehabilitation for subacute low back pain among working age adults. SEARCH
      STRATEGY: The reviewed studies for this structured Cochrane review were
      identified from electronic bibliographic databases, the Science Citation Index,
      reference checking and consulting experts in the rehabilitation field. The
      original search was planned and performed for more broad area of musculoskeletal
      disorders. Trials on subacute low back pain were separated afterwards. SELECTION
      CRITERIA: From all references found in our original search we selected randomized
      controlled trials (RCTs) and non-randomized controlled clinical trials (CCTs).
      Trials had to assess the effectiveness of multidisciplinary rehabilitation for
      working age patients suffering from subacute low back pain (more than 4 weeks but
      less than 3 months). The rehabilitation program was required to be
      multidisciplinary, i.e.; it had to consist of a physician's consultation plus
      either a psychological, social or vocational intervention, or a combination of
      these. DATA COLLECTION AND ANALYSIS: Four blinded reviewers selected the
      randomized controlled trials and controlled trials that met the specified
      inclusion criteria. Two experts in the field of rehabilitation evaluated the
      clinical relevance and applicability of the findings of the selected studies to
      actual clinical use. Two other blinded reviewers extracted the data and assessed
      the main results and the methodological quality of the studies using standardized
      forms. Finally, a qualitative analysis was performed to evaluate the level of
      scientific evidence for the effectiveness of multidisciplinary rehabilitation.
      MAIN RESULTS: After screening 1808 abstracts, and the references of 65 reviews,
      we found only 2 relevant studies that satisfied our criteria on subacute low back
      pain. They were both considered to be methodologically low quality randomized
      controlled trials. The clinical relevance of included studies was sufficient. The
      level of scientific evidence for the effectiveness of multidisciplinary
      rehabilitation was moderate on subacute low back pain showing that
      multidisciplinary rehabilitation which includes workplace visit or more
      comprehensive occupational health care intervention helps patients to return to
      work faster, makes sick leaves less and alleviates subjective disability.
      REVIEWER'S CONCLUSIONS: We conclude that there is moderate evidence of positive
      effectiveness of multidisciplinary rehabilitation for subacute low back pain and
      workplace visit increases the effectiveness. But because this evidence is based
      on the trials that had some methodological shortcomings and several expensive
      multidisciplinary rehabilitation programmes are commonly used for common subacute
      low back problems, there is an obvious need for high quality trials in this
      field.

PMID- 10908529
TI  - Multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain among
      working age adults.
AB  - BACKGROUND: Multidisciplinary biopsychosocial rehabilitation programs for neck
      and shoulder pain require substantial staff and financial resources. Despite
      questionable scientific evidence of their effectiveness, they are widely used.
      Neck and shoulder complaints are common among working age adults and they are
      often associated with physical work load and stress. Pain in the neck and
      shoulder area cause biopsychosocial difficulties for the patient especially if
      disability due to pain is prolonged. To help patients with biopsychosocial
      problems or to prevent their development, multidisciplinary biopsychosocial
      programs are applied on rehabilitation for neck and shoulder pain patients.
      Nevertheless multidisciplinary treatment programmes are often laborious and
      rather long processes and require good collaboration between the patient, the
      rehabilitation team and the work place. OBJECTIVES: The objective of this
      systematic review was to determine the effectiveness of multidisciplinary
      biopsychosocial rehabilitation for neck and shoulder pain among working age
      adults. SEARCH STRATEGY: The reviewed studies for this structured Cochrane review
      were identified from electronic bibliographic databases, the Science Citation
      Index, reference checking and consulting experts in the rehabilitation field. The
      original search was planned and performed for more broad area of musculoskeletal
      disorders. Trials on neck and shoulder pain were separated afterwards. SELECTION
      CRITERIA: From all references found in our original search we selected randomized
      controlled trials (RCTs) and non-randomized controlled clinical trials (CCTs).
      Trials had to assess the effectiveness of biopsychosocial rehabilitation for
      patients suffering from neck and shoulder pain among working age adults. The
      rehabilitation program was required to be multidisciplinary, i.e.; it had to
      consist of a physician's consultation plus either a psychological, social or
      vocational intervention, or a combination of these. DATA COLLECTION AND ANALYSIS:
      Four blinded reviewers selected the randomized controlled trials and controlled
      trials that met the specified inclusion criteria. Two experts in the field of
      rehabilitation evaluated the clinical relevance and applicability of the findings
      of the selected studies to actual clinical use. Two other blinded reviewers
      extracted the data and assessed the main results and the methodological quality
      of the studies using standardized forms. Finally, a qualitative analysis was
      performed to evaluate the level of scientific evidence for the effectiveness of
      multidisciplinary biopsychosocial rehabilitation. MAIN RESULTS: After screening
      1808 abstracts, and the references of 65 reviews, we found only 2 relevant
      studies that satisfied our criteria. One of these was considered methodologically
      low quality randomized controlled trial and the other one was a methodologically
      low quality controlled clinical trial. The clinical relevance of included studies
      was satisfactory. The level of scientific evidence for the effectiveness of
      multidisciplinary biopsychosocial rehabilitation was limited for neck and
      shoulder pain. REVIEWER'S CONCLUSIONS: We conclude that there appears to be
      little scientific evidence for the effectiveness of multidisciplinary
      biopsychosocial rehabilitation compared with other rehabilitation facilities on
      neck and shoulder pain. Multidisciplinary rehabilitation is a commonly used
      intervention for chronic neck and shoulder complaints, therefore we see an urgent
      need for high quality trials in this field.

PMID- 10908530
TI  - Macrolide antibiotics for cystic fibrosis.
AB  - BACKGROUND: Cystic Fibrosis is characterised by chest infection, the antibiotic
      treatment of which has significantly improved the outlook for people with this
      condition. The unusual nature of organisms that infect the chest of individuals
      with cystic fibrosis has restricted antibiotic choice. In particular the
      bacteria, Pseudomonas aeruginosa, is resistant to nearly all antibiotics that can
      be taken by mouth. There is laboratory evidence and evidence from other disease
      processes that macrolide antibiotics, whilst not directly active against
      Pseudomonas aeruginosa, may have indirect actions against this bacteria.
      OBJECTIVES: This review aimed to test the hypotheses that macrolide antibiotics;
      1) Improve clinical status compared to placebo or another antibiotic 2) do not
      have unacceptable adverse effects If benefit was demonstrated, we aimed to assess
      the optimal type, dose and duration of macrolide therapy. SEARCH STRATEGY: We
      searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist
      trials register which comprises references identified from comprehensive
      electronic database searches, handsearching relevant journals and handsearching
      abstract books of conference proceedings. In addition, Principal Investigators,
      known to work in the field and previous authors were contacted for unpublished or
      follow up data. Pharmaceutical companies, that manufacture macrolide antibiotics,
      were approached. SELECTION CRITERIA: Randomised controlled trials, published or
      unpublished, of macrolide compared to placebo, another class of antibiotic or
      another macrolide. Studies which compare regimes of the same macrolide at
      different doses will also be included. DATA COLLECTION AND ANALYSIS: No completed
      randomised controlled trials were identified. MAIN RESULTS: Three open studies
      excluded. Four ongoing randomised controlled trials were identified. No completed
      randomised controlled trials were identified. REVIEWER'S CONCLUSIONS: At present,
      there are no randomised controlled trials to evaluate the use of macrolide
      antibiotics for the treatment of chest infection in people with cystic fibrosis.
      Such trials, with clear outcome measures, are needed to properly evaluate this
      potentially useful treatment for cystic fibrosis.

PMID- 10908531
TI  - Capitation, salary, fee-for-service and mixed systems of payment: effects on the
      behaviour of primary care physicians.
AB  - BACKGROUND: It is widely believed that the method of payment of physicians may
      affect their clinical behaviour. Although payment systems may be used to achieve
      policy objectives (e.g. cost containment or improved quality of care), little is
      known about the effects of different payment systems in achieving these
      objectives. OBJECTIVES: To evaluate the impact of different methods of payment
      (capitation, salary, fee for service and mixed systems of payment) on the
      clinical behaviour of primary care physicians (PCPs). SEARCH STRATEGY: We
      searched the Cochrane Effective Practice and Organisation of Care Group
      specialised register; the Cochrane Controlled Trials Register; MEDLINE (1966 to
      October 1997); BIDS EMBASE (1980 to October 1997); BIDS ISI (1981 to October
      1997); EconLit (1969 to October 1997); HealthStar (1975 to October 1997) Helmis
      (1984 to October 1997); health economics discussion paper series of the
      Universities of York, Aberdeen, Sheffield, Bristol, Brunel, and McMaster; Swedish
      Institute of Health Economics; RAND corporation; and reference lists of articles.
      SELECTION CRITERIA: Randomised trials, controlled before and after studies and
      interrupted time series analyses of interventions comparing the impact of
      capitation, salary, fee for service (FFS) and mixed systems of payment on primary
      care physician satisfaction with working environment; cost and quantity of care;
      type and pattern of care; equity of care; and patient health status and
      satisfaction. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted
      data and assessed study quality. MAIN RESULTS: Four studies were included
      involving 640 primary care physicians and more than 6400 patients. There was
      considerable variation in study setting and the range of outcomes measured. FFS
      resulted in more primary care visits/contacts, visits to specialists and
      diagnostic and curative services but fewer hospital referrals and repeat
      prescriptions compared with capitation. Compliance with a recommended number of
      visits was higher under FFS compared with capitation payment. FFS resulted in
      more patient visits, greater continuity of care, higher compliance with a
      recommended number of visits, but patients were less satisfied with access to
      their physician compared with salaried payment. REVIEWER'S CONCLUSIONS: It is
      noteworthy that so few studies met the inclusion criteria. There is some evidence
      to suggest that the method of payment of primary care physicians affects their
      behaviour, but the findings' generalisability is unknown. More evaluations of the
      effect of payment systems on PCP behaviour are needed, especially in terms of the
      relative impact of salary versus capitation payments.

PMID- 10908532
TI  - Primary groin irradiation vs primary groin surgery for early vulvar cancer.
AB  - BACKGROUND: Despite changes in technique, morbidity after surgical treatment for
      vulvar cancer is considerable and mainly related to the groin dissection. Primary
      radiotherapy to the groin is expected to result in lower morbidity. However,
      studies on the efficacy of primary radiotherapy for the groins in terms of groin
      recurrences and survival show conflicting results. OBJECTIVES: To determine
      whether the effectiveness and safety of primary radiotherapy to the inguino
      femoral lymph nodes is comparable with surgery SEARCH STRATEGY: The literature
      search was carried out using the criteria set by the Cochrane Gynaecological
      Cancer Group. A MEDLINE and EMBASE search using the Mesh Heading 'vulvar
      neoplasms' and textword 'vulva' was performed. Publications on the effectiveness
      of primary radiotherapy treatment of early squamous cell carcinoma of the vulva
      were selected. SELECTION CRITERIA:  TYPE OF STUDY: Randomized clinical trials,
      case-control and observational studies of primary radiotherapy of the groin Type
      of participants: Patients with early squamous cell cancer of the vulva Type of
      interventions: inguino-femoral lymph node dissection and primary radiotherapy of
      the inguino-femoral lymph nodes. Type of outcome measurements: incidence of groin
      recurrences, survival and morbidity DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed study quality and extracted results MAIN RESULTS: Out of
      nine reviewed papers only three met the selection criteria. From these studies,
      (one randomised controlled trial ?RCT? one case-control and one observational
      study) it became clear from the RCT that the incidence of groin recurrences after
      primary radiotherapy is higher compared with surgery. survival was also worse in
      the radiotherapy group. The other two studies showed a higher than expected
      number of groin recurrences after primary radiotherapy. Morbidity after primary
      radiotherapy was lower compared with surgery. The conclusion of the RCT was
      criticized on the grounds of the depth of the radiotherapy administered. The
      depth of 3 cm used in the RCT, is too shallow to administer an optimal dose to
      the deeper groin nodes. REVIEWER'S CONCLUSIONS: As shown in an RCT, primary
      radiotherapy to the groin results in less morbidity but also in a higher number
      of groin recurrences compared with surgery. Although the technique of
      radiotherapy in the RCT was criticized, other uncontrolled data do not give
      evidence for a similar or better groin control for radiotherapy when compared to
      surgery. This means that surgery is still to be considered the cornerstone of
      therapy for the groin nodes in women with vulvar cancer. Individual patients not
      fit enough to withstand surgery can be treated with primary radiotherapy.

PMID- 10908533
TI  - Drugs for nocturnal enuresis in children (other than desmopressin and
      tricyclics).
AB  - BACKGROUND: Enuresis (bedwetting) is a socially unacceptable and stressful
      condition which affects around 15-20% of five year olds, and up to 2% of young
      adults. Although there is a high rate of spontaneous remission, the social,
      emotional and psychological costs to the children can be great. OBJECTIVES: To
      assess the effects of drugs other than desmopressin and tricyclics on nocturnal
      enuresis in children, and to compare them with other interventions. SEARCH
      STRATEGY: The following electronic databases were searched: MEDLINE to June 1997;
      AMED; ASSIA; BIDS; BIOSIS Previews (1985-1996); CINAHL; DHSS Data; EMBASE (1974
      to June 1997); PsycLIT and SIGLE. Organisations, manufacturers, researchers and
      health professionals concerned with enuresis were contacted for information. The
      reference sections of obtained studies were also checked for further trials. Date
      of the most recent search: July 1997. SELECTION CRITERIA: All randomised trials
      of drugs (excluding desmopressin or tricyclics) for nocturnal enuresis in
      children were included in the review. Trials were eligible for inclusion if:
      children were randomised to receive drugs compared with placebo, other drugs or
      other conservative interventions for nocturnal bedwetting; participants with
      organic causes for their bedwetting were excluded; and baseline assessments of
      the level of bedwetting were provided. Trials focused solely on daytime wetting
      were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      the quality of the eligible trials, and extracted data. MAIN RESULTS: None of the
      drugs (phenmetrazine, amphetamine sulphate/ephedrine + atropine, furosemide (sic)
      or chlorprotixine) were better than placebo during treatment. The numbers were
      too small to draw reliable conclusions, and none are used in current practice in
      the UK. Imipramine (a tricyclic) was better than each of the three drugs with
      which it was compared (meprobamate, ephedrine sulphate and furosemide) even
      though the numbers were small. Alarm treatment was better than drugs in one small
      trial. REVIEWER'S CONCLUSIONS: There was not enough evidence to suggest that the
      included drugs reduced bedwetting. There was limited evidence to suggest that
      imipramine and alarms were better, and in other reviews, desmopressin, tricyclics
      and alarm interventions have tentatively been shown to be effective.

PMID- 10908534
TI  - Antibiotic treatment for travellers' diarrhoea.
AB  - BACKGROUND: Traveller's diarrhoea is a syndrome frequently encountered in persons
      crossing an international boundary. Diarrhoea can lead to significant discomfort
      and interference with travel plans. Bacterial pathogens are a frequent cause of
      this syndrome. Several antibiotics have been tested for efficacy in reducing the
      duration and severity of the illness. OBJECTIVES: The aims of this review were to
      assess the effects of antibiotics on traveller's diarrhoea in relation to
      duration of illness, severity of illness, and adverse effects of medications.
      SEARCH STRATEGY: The Cochrane Collaboration Trials Register, MEDLINE, and EMBASE
      were searched. Additional trials were identified by hand searching. Content
      experts were contacted. SELECTION CRITERIA: All trials in any language in which
      travellers older than 5 years were randomly allocated to treatment for acute non
      bloody diarrhoea with antibiotics and where the causative organism is not known
      at allocation. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality
      and extracted data. MAIN RESULTS: Twenty published studies met inclusion and
      quality criteria for inclusion. Twelve studies were placebo-controlled. A meta
      analysis for the primary outcome was not feasible. All of the 10 trials reported
      a significant reduction in duration of diarrhoea in participants treated with
      antibiotics compared with placebo. Data from two trials demonstrated a small
      reduction for antibiotic treated patients in the number of unformed stools passed
      per each 24 hour period from randomisation up to 72 hours. Data from six trials
      demonstrated a greater number of participants being cured of diarrhoea by 72
      hours (odds ratio [OR] 5. 9, 95% confidence interval [CI] 4.06 to 8.57). Data
      regarding side effects were available from five trials. There was wide variation
      in the prevalence of side effects reported in different trials. Persons taking
      antibiotics experienced more side effects than those taking placebo (OR 2.37, 95%
      CI 1.5 to 3.75). REVIEWER'S CONCLUSIONS: Antibiotic treatment is associated with
      shorter duration of diarrhoea but higher incidence of side-effects. Trials
      generally do not report duration of post-treatment diarrhoea using time-to-event
      analyses, and should do.

PMID- 10908535
TI  - Steroids for treating tuberculous meningitis.
AB  - BACKGROUND: Even though corticosteroids have been used alongside antituberculosis
      drugs for tuberculous meningitis (TBM) since the 1950s their role remains
      controversial. Some believe corticosteroids improve outcome while others point to
      the lack of supportive evidence. In patients who are immunocompromised because of
      HIV infection the risks and benefits of steroids are unknown. OBJECTIVES: To
      assess the effects of steroids on death and disability in patients with TBM.
      SEARCH STRATEGY: Electronic searching of MEDLINE, Cochrane Controlled Trials
      Register, and Cochrane Infectious Diseases Group Trials Register. SELECTION
      CRITERIA: Randomised controlled trials of steroids in people on TB treatment for
      TBM. DATA COLLECTION AND ANALYSIS: Two independent reviewers applied study
      selection criteria, assessed methodological quality and extracted data. MAIN
      RESULTS: Six trials of 595 patients met the inclusion criteria. No study
      described allocation concealment. Steroids were associated with fewer deaths
      (relative risk [RR] 0.79; 95% confidence interval [CI] 0.65 to 0.97) and a
      reduced incidence of death and severe residual disability (RR 0.58, 95% CI 0.38
      to 0.88). Subgroup analysis suggests an effect on mortality in children (RR 0.77,
      95% CI 0.62 to 0.96) but the results in a smaller number of adults are
      inconclusive (RR 0.96, 95% CI 0.50 to 1.84). There is little evidence that the
      severity of disease influences the effects of steroids on mortality. REVIEWER'S
      CONCLUSIONS: Adjunctive steroids might be of benefit in patients with TBM.
      However, existing studies are small, and poor allocation concealment and
      publication bias may account for the positive results found in this review. No
      data are available on the use of steroids in HIV positive persons. Future placebo
      controlled studies should include patients with HIV infection and should be large
      enough to assess both mortality and disability.

PMID- 10908536
TI  - Near-infrared spectroscopy for fetal assessment during labour.
AB  - BACKGROUND: Over the past four decades, continuous electronic fetal monitoring
      (EFM) has been increasingly employed to detect fetal acidemia in labor, with a
      view toward prevention of hypoxic ischemic encephalopathy, permanent neurologic
      injury, and death. Although very sensitive, this technology has low specificity,
      and a high false positive rate. This false positive rate has resulted in
      operative intervention on behalf of many fetuses who were not in fact in danger
      of neurologic injury or death. Near-infrared spectroscopy has been developed to
      directly measure fetal cerebral oxygenation, with a view toward identification of
      those fetuses truly at risk. OBJECTIVES: To determine the effects of the use of
      near-infrared spectroscopy (NIRS) to assess fetal condition during labour, on
      maternal and perinatal outcomes. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials
      Register. Date of last search: November 1999. SELECTION CRITERIA: Randomized
      trials comparing near-infrared spectroscopy with continuous EFM alone or
      continuous EFM and scalp pH. DATA COLLECTION AND ANALYSIS: Eligibility and trial
      quality were assessed by one reviewer. MAIN RESULTS: No randomized trials were
      identified. Thus no studies were included. REVIEWER'S CONCLUSIONS: There is
      currently insufficient evidence to assess the efficacy of fetal surveillance by
      near-infrared spectroscopy.

PMID- 10908537
TI  - Treatments for symptomatic urinary tract infections during pregnancy.
AB  - BACKGROUND: Urinary tract infections, including pyelonephritis, are serious
      complications that can result in significant maternal and neonatal morbidity and
      mortality. There is a large number of drugs, and combination of them, available
      to treat urinary tract infections, most of them tested in non-pregnant women.
      Attempts to define the optimal antibiotic regimen for pregnancy has, therefore,
      been problematic. OBJECTIVES: The objective of this review was to try to
      determine, from the best available evidence from randomized control trials, which
      agent is most effective for the treatment of symptomatic urinary tract infections
      during pregnancy in terms of cure rates, recurrent infection, incidence of
      preterm delivery and premature rupture of membranes, admission to neonatal
      intensive care unit, need for change of antibiotic, and incidence of prolonged
      pyrexia. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials
      register, the Cochrane Controlled Trials Register and reference lists of articles
      were searched. SELECTION CRITERIA: All trials were considered where the intention
      was to allocate participants randomly to one of at least two alternative
      treatments for any symptomatic urinary tract infection. DATA COLLECTION AND
      ANALYSIS: Trial quality assessment and data extraction were performed by the two
      reviewers. MAIN RESULTS: Five studies were included. There were no significant
      differences between studied treatments with regard to cure rates, recurrent
      infection, incidence of preterm delivery and premature rupture of membranes,
      admission to neonatal intensive care unit, need for change antibiotic and
      incidence of incidence of prolonged pyrexia. REVIEWER'S CONCLUSIONS: Although
      antibiotic treatment is effective for the cure of urinary tract infections, there
      are insufficient data to recommend any specific treatment regimen for symptomatic
      urinary tract infections during pregnancy. All of the antibiotics studied were
      shown to be very effective in decreasing the incidence of outcomes measured.
      Complications were very rare. All included trials had very small sample sizes to
      try to detect important differences between treatments. Future studies should
      evaluate the most promising antibiotics, in terms of class, timing, dose,
      acceptability, maternal and neonatal outcomes and costs.

PMID- 10908539
TI  - Pramipexole versus bromocriptine for levodopa-induced complications in
      Parkinson's disease.
AB  - OBJECTIVES: To compare the efficacy and safety of adjuvant pramipexole versus
      bromocriptine therapy in patients with Parkinson's disease, already established
      on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic
      searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register.
      Handsearching of the neurology literature as part of the Cochrane Movement
      Disorders Group's strategy. Examination of the reference lists of identified
      studies and other reviews. Contact with Pharmacia Upjohn and Boehringer
      Ingelheim. SELECTION CRITERIA: Randomised controlled trials of pramipexole versus
      bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's
      disease and long-term complications of levodopa therapy. DATA COLLECTION AND
      ANALYSIS: Data was abstracted independently by the authors and differences
      settled by discussion. The outcome measures used included Parkinson's disease
      rating scales, levodopa dosage, 'off' time measurements and the frequency of drop
      outs and adverse events. MAIN RESULTS: One randomised controlled trial has
      compared pramipexole with bromocriptine using a double-blind, parallel group,
      multicentre design. It was not powered to examine differences between active
      treatment arms. There was a larger reduction in off time with pramipexole therapy
      compared with bromocriptine (weighted mean difference 1.4 hours; 0, 2.8, 95% CI).
      No differences occurred in dyskinesia rating scale, dyskinesia as an adverse
      event or UPDRS complication score. The UPDRS ADL and motor scores showed similar
      improvements compared to placebo with both agonists. Levodopa dose reduction was
      similar with both agonists. Subscales of the Functional Status Questionnaire
      showed significant improvements compared to placebo with both agonists. The
      finding that the EuroQol improved significantly compared with placebo with
      pramipexole but not bromocriptine should be treated with caution. Dopaminergic
      adverse events were similar with each agonist, as was the all cause withdrawal
      rate. REVIEWER'S CONCLUSIONS: Although pramipexole and bromocriptine improved off
      time and reduced parkinsonian motor impairments and disability compared with
      placebo, no conclusions regarding their comparative effectiveness and safety can
      be drawn as this single trial did not have adequate power to assess such
      differences. Further larger trials are required to examine this issue in the
      future.

PMID- 10908538
TI  - Bromocriptine versus levodopa in early Parkinson's disease.
AB  - BACKGROUND: Drugs that mimic dopamine as bromocriptine were introduced as
      monotherapy or in a combination with LD in the hope that this approach would
      prevent or delay the onset of motor complications in patients with Parkinson's
      disease (PD). However, hitherto, the role of bromocriptine (BR) in this issue has
      remained controversial. The present study is a systematic review of all
      randomized controlled trials of bromocriptine monotherapy compared with levodopa
      (LD) monotherapy in PD. OBJECTIVES: To assess the efficacy and safety of
      bromocriptine (BR) monotherapy for delaying the onset of motor complications
      associated with levodopa (LD) therapy in patients with Parkinson's disease (PD).
      SEARCH STRATEGY: Sources including the Cochrane Library, the search strategy of
      the Movement Disorders Group (includes computerised searches of MEDLINE and
      EMBASE and hand searching of appropriate neurology journals), reference lists of
      the reviews found by the MEDLINE and EMBASE search-strategy, Sandoz -now Novartis
      (manufacturer of BR), symposia reports, PD handbooks, contacts with colleagues
      who had co-ordinated trials on BR and reference lists of all included studies
      were used to identify randomized controlled trials (RCTs) of interest. SELECTION
      CRITERIA: Randomized trials were eligible for inclusion if they evaluated the
      efficacy of BR monotherapy for delaying the onset of motor complications compared
      to LD therapy in PD patients. Outcome measures that were evaluated included
      occurrence and severity of motor complications, changes in impairment and
      disability, and the occurrence of side effects. DATA COLLECTION AND ANALYSIS: To
      determine the feasibility of a quantitative systematic review two independent
      reviewers evaluated the methodological quality of identified trials. MAIN
      RESULTS: Over the period of 1974 to January 1999 we identified six studies
      randomizing more than 850 patients to a BR or a LD regimen. The majority of the
      studies lacked sample size calculations and randomization procedure remained
      unclear in three trials. Only two trials were performed according to a double
      blind design. Important differences between studies concerning the duration of
      trials, the BR titration phase, the achieved mean dose of LD or BR, and the
      applied outcomes were found. Because of these differences, we could not pool the
      data from the different trials in an attempt to perform a meta-analysis.
      Therefore, the available data of the individual trials was re-analysed.
      Subsequently, the results were interpreted against the background of the sources
      of heterogeneity between the studies. The occurrence of dyskinesias in three
      short trials was too low to allow any conclusion. The results of the longer
      trials indicate a lower occurrence of dyskinesias in the BR tier. In five trials
      that evaluated dystonia, this motor complication occurred less frequent in the BR
      tier. However, for both dyskinesias and dystonia a statistically significant
      difference in favour of BR emerged only in the largest trial. There was a trend
      for wearing-off and on-off fluctuations to occur less frequently in the BR group.
      Although all trials evaluated patients at the impairment level, only the largest
      trial reported a significantly larger improvement for the LD tier during the
      first year of therapy. Concerning disability, which was evaluated by five trials
      no statistically significant differences were found. Overall, a statistically
      larger number of dropouts occurred in the BR group because of an inadequate
      therapeutic response or intolerable side effects. REVIEWER'S CONCLUSIONS: This
      systematic review identified important sources of heterogeneity between trials.
      Inadequate powering of the studies and clinically relevant differences in trial
      duration, applied outcomes, and trial design may explain the different results
      and why many findings failed to reach a statistically significant level.
      Nevertheless, based on qualitative review of available data we conclude that in
      the treatment of early Parkinson's disease, bromocriptine may be beneficial in
      delaying motor complications and dyskinesias with comparable effects on
      impairment and disability in those patients that tolerate the drug.

PMID- 10908540
TI  - Pramipexole for levodopa-induced complications in Parkinson's disease.
AB  - OBJECTIVES: To compare the efficacy and safety of adjuvant pramipexole therapy
      versus inactive placebo in patients with Parkinson's disease, already established
      on levodopa. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the
      Cochrane Controlled Trials Register. Handsearching of the neurology literature as
      part of the Cochrane Movement Disorders Group's strategy. Examination of the
      reference lists of identified studies and other reviews. Contact with Pharmacia
      Upjohn and Boehringer Ingelheim. SELECTION CRITERIA: Randomised controlled trials
      of pramipexole versus placebo in patients with a clinical diagnosis of idiopathic
      Parkinson's disease and long-term complications of levodopa therapy. DATA
      COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and
      differences settled by discussion. The outcome measures used included Parkinson's
      disease rating scales, levodopa dosage, 'off' time measurements and the frequency
      of drop outs and adverse events. MAIN RESULTS: Four randomised controlled trials
      have compared pramipexole with placebo in 669 patients with later Parkinson's
      disease. Two phase III studies were medium term (24 weeks maintenance period) and
      2 phase II studies were short term (4 weeks maintenance period). The reduction in
      off time was significantly greater with pramipexole compared with placebo
      (weighted mean difference 1.8 hours; 1.2, 2.3 95% CI). No significant changes
      were noted in a dyskinesia rating scale in any of the 4 studies, but dyskinesia
      as an adverse event was reported more frequently with pramipexole. A significant
      improvement occurred in UPDRS complication score (part IV) in 2 studies but not
      in the remaining trials. Statistically significant improvements in UPDRS ADL
      score occurred with pramipexole in all studies. Significant improvements in UPDRS
      motor scores in the on state were reported in 3 of the 4 studies. Levodopa dose
      reduction was allowed in 3 studies and meta-analysis shows a significant
      difference in favour of pramipexole (weighted mean difference 115 mg; 87, 143 95%
      CI). Trends toward a higher incidence of dopaminergic adverse events with
      pramipexole only reached statistical significance regarding hallucinations. There
      were significantly fewer withdrawals from pramipexole. REVIEWER'S CONCLUSIONS:
      Pramipexole can be used to reduce off time, improve motor impairments and
      disability and reduce levodopa dose at the expense of increased dyskinetic
      adverse events. This conclusion is based on short and medium term trials (up to
      24 weeks). Further trials are required to directly compare the newer with the
      older dopamine agonists.

PMID- 10908541
TI  - Cyclophosphamide versus methylprednisolone for the treatment of neuropsychiatric
      involvement in systemic lupus erythematosus.
AB  - BACKGROUND: Neuropsychiatric involvement in systemic lupus erythematosus is
      complex and several clinical presentations are related to this disease such as:
      convulsions, chronic headache, transverse myelitis, vascular brain disease,
      psychosis and neural cognitive dysfunction. OBJECTIVES: To assess the efficacy
      and safety of cyclophosphamide and methylprednisolone in the treatment of
      neuropsychiatric manifestations of systemic lupus erythematosus on mortality and
      side effects. SEARCH STRATEGY: We searched EMBASE, LILACS, Cochrane Controlled
      Trials Register and MEDLINE up to and including December 1999, additional
      articles were sought through handsearching in relevant journals, using the search
      strategy described in the Cochrane Handbook [Dickersin 1994]. There were no
      language restrictions. SELECTION CRITERIA: All randomized controlled trials which
      compared cyclophosphamide to methylprednisolone were to be included. Patients of
      any age and gender were included if they fulfilled the criterion of the American
      Rheumatology Association for the diagnosis of systemic lupus erythematosus and
      presented with any one of the following neuropsychiatric events; convulsions,
      organic brain syndrome; cranial neuropathy. Outcome measures included the
      following: a) Overall mortality (primary event); b) Motor and psychiatric deficit
      (primary event); c) Clinical improvement (secondary event). DATA COLLECTION AND
      ANALYSIS: The analysis planned was to do the following: Data would be
      independently extracted by the two reviewers and cross-checked. The
      methodological quality of each trial would be assessed by the same two reviewers.
      Details of the randomisation (generation and concealment), blinding, and the
      number of patients lost on follow-up would be recorded. The results of each RCT
      would be summarised on an intention-to-treat basis in 2 x 2 tables for each
      outcome. External validity would be defined by characteristics of the
      participants, the interventions and the outcomes. If appropriate, RCTs would be
      stratified based on control group and category of disease in accordance to the
      clinical homogeneity (external validity). The results obtained from these
      different methods are very similar, and therefore, only the results from the Risk
      Difference method, with the corresponding 95% confidence interval would be
      presented in this review. The fixed effects model would be used if there was no
      significant statistical heterogeneity. MAIN RESULTS: We found no randomised
      controlled trials comparing cyclophosphamide versus methylprednisolone for the
      treatment of neuropsychiatric involvement in the systemic lupus erythematosus.
      REVIEWER'S CONCLUSIONS: Cyclophosphamide regimen treatment is a form of care in
      neuropsychiatric involvement in systemic lupus erythematosus with no evidence to
      prove better effectiveness and safety when compared with methylprednisolone. This
      systematic review found no randomised controlled trials and its findings must be
      interpreted as 'no evidence of effect' and not as 'evidence of no effect'.

PMID- 10908542
TI  - Biopsychosocial rehabilitation for upper limb repetitive strain injuries in
      working age adults.
AB  - BACKGROUND: Upper limb repetitive strain injury is a common problem in western
      countries, causing human suffering and huge economical losses. Patients with
      prolonged pain associated with repetitive tasks in the work place can face both
      psychological and physical difficulties. Different treatment programmes,
      physical, psychological, behavioural, social and occupational treatments have
      been developed and used to help these patients. OBJECTIVES: The objective of this
      systematic review is to determine the effectiveness of biopsychosocial
      rehabilitation for upper limb repetitive strain injuries among working age
      adults. SEARCH STRATEGY: The reviewed studies for this structured Cochrane review
      were identified from electronic bibliographic databases, the Science Citation
      Index, reference checking and consulting experts in the rehabilitation field. The
      original search was planned and performed for a more broad area of
      musculoskeletal disorders. Trials on repetitive strain injuries were separated
      afterwards. SELECTION CRITERIA: Randomised controlled trials and controlled
      trials comparing biopsychosocial measures for the treatment of repetitive upper
      limb strain injury in working age adults DATA COLLECTION AND ANALYSIS: Two
      experts in the field of rehabilitation evaluated the clinical relevance and
      applicability of the findings of the selected studies to actual clinical use. Two
      other blinded reviewers extracted the data and assessed the main results and the
      methodological quality of the studies using standardized forms. Finally, a
      qualitative analysis was performed to evaluate the level of scientific evidence
      for the effectiveness of biopsychosocial rehabilitation. MAIN RESULTS: We found
      only two relevant studies that satisfied our criteria. They assessed the
      effectiveness of two specific interventions and were both considered as low
      quality trials. The clinical relevance of the included studies was also
      unsatisfactory. The level of scientific evidence for the effectiveness of
      biopsychosocial rehabilitation for repetitive strain injuries was limited. One
      small trial found that hypnosis supplementary to comprehensive treatment can
      decrease the intensity of pain for acute RSI in six weeks follow-up. REVIEWER'S
      CONCLUSIONS: We conclude that presently there appears to be little scientific
      evidence for the effectiveness of biopsychosocial rehabilitation on repetitive
      strain injuries. As RCTs on more intensive and comprehensive biopsychosocial
      treatment programmes for RSI are lacking, there does not seem to be reliable data
      for these interventions. There is a need for high quality trials in this field.

PMID- 10908543
TI  - Continuous distending airway pressure for respiratory distress syndrome in
      preterm infants.
AB  - BACKGROUND: Respiratory distress syndrome (RDS) is the single most important
      cause of morbidity and mortality in preterm infants (Greenough 1998, Bancalari
      1992). Intermittent positive pressure ventilation (IPPV) with surfactant is the
      standard treatment for the condition. The major difficulty with IPPV is that it
      is invasive, resulting in airway and lung injury and contributing to the
      development of chronic lung disease. OBJECTIVES: In spontaneously breathing
      preterm infants with RDS, to determine if continuous distending airway pressure
      (CDAP) reduces the need for IPPV and associated morbidity without adverse
      effects. SEARCH STRATEGY: The standard search strategy of the Neonatal Review
      group was used. This included searches of the Oxford Database of Perinatal
      Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including
      cross references, abstracts, conference and symposia proceedings, expert
      informants, journal hand searching mainly in the English language. SELECTION
      CRITERIA: All trials using random or quasi-random patient allocation of newborn
      infants with RDS were eligible. Interventions were continuous distending airway
      pressure including continuous positive airway pressure (CPAP) by mask, nasal
      prong, nasopharnygeal tube, or endotracheal tube, or continuous negative pressure
      (CNDP) via a chamber enclosing the thorax and lower body, compared with standard
      care. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane
      Collaboration and its Neonatal Review Group, including independent assessment of
      trial quality and extraction of data by each author, were used. MAIN RESULTS:
      CDAP is associated with a lower rate of failed treatment (death or use of
      assisted ventilation), overall mortality, and mortality in infants with
      birthweights above 1500 g. The use of CDAP is associated with an increased rate
      of pneumothorax. REVIEWER'S CONCLUSIONS: In preterm infants with RDS the
      application of CDAP either as CPAP or CNDP is associated with some benefits,
      particularly in infants with birthweights over 1500 gms. The extent of this
      benefit is difficult to assess given the outdated methods to administer CDAP, low
      use of antenatal corticosteroids, non-availability of surfactant and the
      intensive care setting of the 1970's in which these trials were done. Where
      resources are limited, such as in developing countries, CPAP for RDS may have a
      clinical role. Further research is required to determine the best mode of
      administration and its role in modern intensive care settings

PMID- 10908544
TI  - Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous
      positive airway pressure (NCPAP) for apnea of prematurity.
AB  - BACKGROUND: Apnea of prematurity is almost universal in infants who are born
      before 34 weeks gestation. Previous randomised trials and systematic reviews have
      found methylxanthines to be effective in preventing apnea of prematurity.
      However, recent concerns about potential long term side effects of
      methylxanthines on the neurodevelopment of low birth weight infants have led to
      an increased interest in alternate methods of treating apnea of prematurity.
      Nasal continuous positive airway pressure (NCPAP) is a useful method of
      respiratory support which reduces the incidence of obstructive or mixed apnea.
      However, apneic infants managed with NCPAP, with or without methylxanthines,
      sometimes require endotracheal intubation with its attendant morbidity and cost.
      Nasal intermittent positive pressure ventilation (NIPPV) is a simple, effective
      mode of respiratory support for older children and adults. It has been used to
      treat apnea in preterm infants but case reports of gastrointestinal perforations
      have limited its widespread use. OBJECTIVES: In preterm infants with recurrent
      apnea, does treatment with NIPPV lead to a greater reduction in apnea and need
      for intubation and mechanical ventilation, as compared with treatment with NCPAP?
      Does NIPPV increase the incidence of gastrointestinal complications, i.e. gastric
      distension leading to cessation of feeds, or perforation? SEARCH STRATEGY:
      Medline was searched (1966-2000) using the MeSH terms: infant, newborn (exp) and
      positive-pressure respiration (exp). Other sources included the Cochrane
      Controlled Trials Register and CINAHL (search terms: infant, newborn and
      intermittent positive pressure ventilation); also used were expert informants,
      previous reviews including cross-references, and conference and symposia
      proceedings. SELECTION CRITERIA: All randomised and quasi-randomised trials were
      included. Participants included unventilated preterm infants experiencing apnea
      of prematurity. Interventions compared were intermittent positive pressure
      ventilation administered via the nasal route, either by short nasal prongs or
      nasopharyngeal tube, and nasal CPAP delivered by the same methods. Types of
      outcome measures: - failure of therapy as defined by apnea that is frequent or
      severe requiring additional ventilatory support - rates of endotracheal
      intubation - rates of apnea and bradycardia expressed as events per hour -
      gastrointestinal complications i.e. abdominal distension requiring cessation of
      feeds, or GI perforation DATA COLLECTION AND ANALYSIS: Data were extracted
      independently by the three reviewers. The trials were analysed using relative
      risk (RR), risk difference (RD) and number needed to treat (NNT) for dichotomous
      data; means and weighted mean difference (WMD) were used for continuous data.
      MAIN RESULTS: Two trials, enrolling 54 infants in total, fulfilled the inclusion
      criteria. Both reported only the short term results (4 to 6 hours) of the
      interventions. Only one infant (randomised to NCPAP) required intubation during
      this period. Ryan (1989), in a cross over study of 20 infants, showed no
      significant difference in rates of apnea (events/hr) between the 2 interventions
      (WMD -0.10 (-0.53,0. 33)). Lin (1998) randomised 34 infants and demonstrated a
      greater reduction in frequency of apneas (events/hr) with NIPPV compared to NCPAP
      (WMD -1.19 (-2.31,-0.07)). Meta-analysis of both trials showed no difference in
      pCO2 (mmHg) at the end of the 4-6 hour study period (WMD 0.95 (-3.05,4.94)). No
      data were reported on gastrointestinal complications. REVIEWER'S CONCLUSIONS: 
      IMPLICATIONS FOR PRACTICE: NIPPV may be a useful method of augmenting the
      beneficial effects of NCPAP in preterm infants with apnea that is frequent or
      severe. Its use appears to reduce the frequency of apneas more effectively than
      NCPAP. Additional safety and efficacy data are required before recommending NIPPV
      as standard therapy for apnea. IMPLICATIONS FOR RESEARCH: Future trials with
      sufficient power should assess the efficacy (reduction in failure of therapy) and
      safety (GI complications) of NIPPV. Outcomes should be assessed throughout the
      entire period during which the infant requires assisted ventilation. The recent
      ability to synchronise NIPPV with an infant's spontaneous respirations is a
      promising development requiring further assessment.

PMID- 10908545
TI  - Feverfew for preventing migraine.
AB  - BACKGROUND: Feverfew (Tanacetum parthenium L.) is a popular herbal remedy for
      migraine. OBJECTIVES: To systematically review the evidence for or against the
      efficacy of feverfew versus placebo for the prevention of migraine. SEARCH
      STRATEGY: Electronic literature searches were performed using the databases
      CISCOM (Research Council for Complementary Medicine, London, UK), MEDLINE,
      EMBASE, Biosis and the Cochrane Library (each from its inception to April 1998).
      Manufacturers were contacted and the bibliographies of identified articles
      checked for further trials. SELECTION CRITERIA: Randomised, placebo-controlled,
      double-blind trials assessing the efficacy of feverfew for preventing migraine
      were included. No restrictions regarding the language of publication were
      imposed. DATA COLLECTION AND ANALYSIS: Data on patients, interventions, methods,
      outcomes and results were extracted in a pre-defined, standardised manner.
      Methodological quality was evaluated using the scoring system developed by Jadad
      and colleagues. Both data extraction and the assessment of methodological quality
      were performed independently by two reviewers. MAIN RESULTS: Four trials met the
      inclusion criteria. The majority of these trials suggested beneficial effects of
      feverfew compared with placebo. However, the trial with the highest
      methodological quality, which was also among the largest, found no significant
      difference between feverfew and placebo. REVIEWER'S CONCLUSIONS: The efficacy of
      feverfew for the prevention of migraine has not been established beyond
      reasonable doubt.

PMID- 10908546
TI  - Cognitive rehabilitation for memory deficits following stroke.
AB  - BACKGROUND: Memory problems occur following stroke. Cognitive rehabilitation
      programmes are provided to retrain memory function or to teach patients
      strategies to cope despite memory impairment. OBJECTIVES: To determine the
      effects of cognitive rehabilitation for memory problems following stroke. SEARCH
      STRATEGY: We searched the Cochrane Stroke Group Trials Register, Medline, EMBASE,
      CINHAL and CLIN PSYCH databases and reference lists from relevant articles. Date
      of most recent searches: December 1998. SELECTION CRITERIA: Controlled trials of
      memory retraining in stroke. Studies with mixed aetiology groups were excluded
      unless they had more than 75% of stroke patients or separate data were available
      for the stroke patients. DATA COLLECTION AND ANALYSIS: Two reviewers extracted
      trial data and assessed trial quality. Reviewers contacted investigators for
      further details of trials. MAIN RESULTS: One trial was identified with 12
      participants. This showed memory strategy training had no significant effect on
      memory impairment or subjective memory complaints. REVIEWER'S CONCLUSIONS: There
      is insufficient evidence to support or refute the effectiveness of cognitive
      rehabilitation for memory problems after stroke.

PMID- 10908547
TI  - Exercise interventions for smoking cessation.
AB  - BACKGROUND: Taking exercise may help people give up smoking by moderating the
      effects of nicotine withdrawal. OBJECTIVES: To determine whether exercise-based
      interventions combined with a smoking cessation programme are more effective than
      a smoking cessation intervention alone. SEARCH STRATEGY: We searched The Cochrane
      Tobacco Addiction group specialised register for studies including the terms
      'exercise' or 'physical activity' in February 2000. SELECTION CRITERIA: We
      included randomised trials comparing an exercise programme as an adjunct to a
      cessation programme with a cessation programme alone, recruiting smokers or
      recent quitters, and with a follow-up of 6 months or more. DATA COLLECTION AND
      ANALYSIS: We extracted data on study characteristics and smoking outcomes.
      Because of differences in studies we summarised the results narratively, making
      no attempt at meta-analysis. MAIN RESULTS: We identified eight trials, six of
      which had fewer than 25 people in each treatment arm. They varied in the timing
      and intensity of the smoking cessation and exercise programmes. Only one trial
      showed a significant benefit from the exercise programme at long term follow-up.
      REVIEWER'S CONCLUSIONS: Only one of the eight trials offered evidence for
      exercise aiding smoking cessation but the other trials were too small to exclude
      reliably an effect of intervention. Trials are needed with larger sample sizes,
      equal contact control conditions, tailored and lifestyle exercise programmes and
      measures of exercise adherence.

PMID- 10908548
TI  - Prevention of chronic NSAID induced upper gastrointestinal toxicity.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are important agents
      in the management of arthritic and inflammatory conditions, and are among the
      most frequently prescribed medications in North America and Europe. However,
      there is overwhelming evidence linking these agents to a variety of
      gastrointestinal (GI) toxicities. OBJECTIVES: To review the effectiveness of
      common interventions for the prevention of NSAID induced upper GI toxicity.
      SEARCH STRATEGY: A literature search was conducted, according to the Cochrane
      methodology for identification of randomized controlled trials in electronic
      databases, including MEDLINE from 1966 to January 2000, Current Contents for 6
      months prior to January 2000, Embase to Febuary 1999, and a search of the
      Cochrane Controlled Trials Register from 1973 to 1999. Recent conference
      proceedings were reviewed and content experts and companies were contacted.
      SELECTION CRITERIA: Randomized controlled clinical trials (RCTs) of prostaglandin
      analogues (PA), H2-receptor antagonists (H2RA) or proton pump inhibitors (PPI)
      for the prevention of chronic NSAID induced upper GI toxicity were included. DATA
      COLLECTION AND ANALYSIS: Two independent reviewers extracted data regarding
      population characteristics, study design, methodological quality and number of
      patients with endoscopic ulcers, ulcer complications, symptoms, overall drop
      outs, drop outs due to symptoms. Dichotomous data was pooled using Revman V3.1.
      Heterogeneity was evaluated using a chi square test. MAIN RESULTS: Thirty-three
      RCTs met the inclusion criteria. All doses of misoprostol significantly reduced
      the risk of endoscopic ulcers. Misoprostol 800 ug/day was superior to 400 ug/day
      for the prevention of endoscopic gastric ulcers (RR=0.18, and RR=0. 38
      respectively, p=0.0055). A dose response relationship was not seen with duodenal
      ulcers. Misoprostol caused diarrhea at all doses, although significantly more at
      800ug/day than 400ug/day (p=0.0012). Misoprostol was the only prophylactic agent
      documented to reduce ulcer complications. Standard doses of H2RAs were effective
      at reducing the risk of endoscopic duodenal (RR=0.24; 95% CI: 0.10-0. 57) but not
      gastric ulcers(RR=0.73; 95% CI:0.50-1.09). Both double dose H2RAs and PPIs were
      effective at reducing the risk of endoscopic duodenal and gastric ulcers
      (RR=0.44; 95% CI:0.26-0.74 and RR=0.37;95% CI;0.27-0.51 respectively for gastric
      ulcer), and were better tolerated than misoprostol. REVIEWER'S CONCLUSIONS:
      Misoprostol, PPIs, and double dose H2RAs are effective at preventing chronic
      NSAID related endoscopic gastric and duodenal ulcers. Lower doses of misoprostol
      are less effective and are still associated with diarrhea. Only Misoprostol
      800ug/day has been directly shown to reduce the risk of ulcer complications.

PMID- 10908549
TI  - Cisapride treatment for gastro-oesophageal reflux in children.
AB  - BACKGROUND: Gastro-oesophageal reflux (GOR) is an extremely common and usually
      self limiting condition in infants. When treatment is required, Cisapride, a pro
      kinetic agent, has been commonly prescribed for the symptomatic management of
      GOR. There have been recent reports of possibly serious adverse events e.g. an
      increased QTc interval, cardiac arrhythmias, and death, associated with the use
      of Cisapride. OBJECTIVES: To determine the effectiveness of Cisapride for
      symptoms of GOR in children compared with placebo or any other non-surgical
      treatments. SEARCH STRATEGY: Searches were conducted of the Cochrane Central
      Trials Register and the specialised Trials register of the Cochrane Upper
      Gastrointestinal and Pancreatic Diseases Group, MEDLINE and Embase. Reference
      lists of relevant review articles and identified trials were scrutinised and
      forward citation searches were performed in the Science Citation Index on all
      trials identified. SELECTION CRITERIA: Randomised controlled trials that compared
      oral Cisapride therapy with placebo or with other non-surgical treatments for
      children with a diagnosis of GOR were included. Only studies in which Cisapride
      was administered orally for a minimum of one week and which documented at least
      one of the primary outcomes were included. DATA COLLECTION AND ANALYSIS: The
      primary outcomes were defined as a change in symptoms at the end of treatment,
      presence of adverse events, occurrence of clinical complications, and weight
      gain. The secondary outcomes included physiological measures of GOR or
      histological evidence of oesophagitis. We dichotomised symptoms into 'same or
      worse' vs 'improved' and calculated summary odds ratios. Continuous measures of
      GOR (e.g. reflux index) were summarised as a weighted mean difference. All
      outcomes were analysed using a random effects method. Sensitivity analyses were
      also performed. MAIN RESULTS: Searches identified eight trials which met the
      inclusion criteria. Seven trials (a total of 236 participants) compared Cisapride
      with placebo. The odds ratio for 'same or worse' vs 'improved symptoms' at the
      end of treatment was 0.34 (95%CI 0.10, 1.19), thus showing no statistically
      significant difference between the two interventions. There was significant
      heterogeneity between the studies and the funnel plot suggested substantial
      publication bias. In the sensitivity analysis, the definition of outcomes was
      changed to 'any symptoms' vs 'no symptoms'. This resulted in the exclusion of
      three trials (one of them the largest, best quality trial). The resulting pooled
      odds ratio showed a significant effect of Cisapride (OR 0.19, 95%CI 0.08, 0.44).
      There were fewer adverse events with placebo than with Cisapride, but the
      difference was not statistically significant (OR 1.80, 95%CI 0.87, 3.70) and the
      result was based on small numbers. Cisapride compared with placebo produced a
      statistically significant reduction in the reflux index (weighted mean difference
      -6.49, 95%CI -10.13, -2.85), but as reflux index and clinical symptoms are poorly
      correlated, the clinical importance of this finding is uncertain. Other measures
      of oesophageal pH monitoring did not reach significance. One included study
      compared Cisapride with Gaviscon (or Gaviscon and Carobel). The odds ratio for
      'same or worse' vs 'improvement' in the Cisapride group compared with Gaviscon
      was 3.26 (95%CI 0.93, 11.38). REVIEWER'S CONCLUSIONS: We found no clear evidence
      that Cisapride reduces symptoms of GOR. The results suggested substantial
      publication bias favouring studies showing a positive effect of Cisapride. Due to
      reports of serious adverse events, the company will stop marketing the drug as of
      July 14th, 2000 and therefore a larger study to provide more conclusive evidence
      of the effect of Cisapride is no longer possible.

PMID- 10908550
TI  - Pressure relieving interventions for preventing and treating diabetic foot
      ulcers.
AB  - BACKGROUND: Foot ulceration is thought to affect 15% of all people with diabetes
      at some time during their life. OBJECTIVES: To assess the effectiveness of
      pressure relieving interventions in the prevention and treatment of diabetic foot
      ulcers. SEARCH STRATEGY: Searches of 19 databases, hand searching of journals,
      bibliographies and identification of unpublished work by written communication
      with recognised experts in the diabetic foot. SELECTION CRITERIA: Randomised
      controlled trials evaluating pressure relieving interventions either in the
      prevention or the treatment of diabetic foot ulcers. There was no restriction on
      articles/trials based on language or publication status. DATA COLLECTION AND
      ANALYSIS: Data extraction and assessment of study quality was undertaken by two
      reviewers independently. Each trial was analysed separately, no pooling of
      results was possible due to the difference in patients, comparisons and outcomes.
      MAIN RESULTS: Prevention 4 RCTs of pressure relieving interventions were
      identified. Interventions for the prevention of diabetic foot ulcers indicated
      that in-shoe orthotics are of benefit. The relative merits of different in-shoe
      orthotics are unclear; cushioning and pressure redistribution appear of equal
      benefit. Other pressure relieving interventions such as running shoes have not
      been adequately evaluated and removable casts (Scotchcast or Hope) or foam inlays
      do not appear to have been evaluated at all in randomised controlled studies.
      Treatment 1 RCT of total contact casting indicated that it was effective in the
      treatment of diabetic ulcers although the evidence was limited. REVIEWER'S
      CONCLUSIONS: Prevention There is limited evidence of the effectiveness of
      orthotic interventions over removal of callus. There is some evidence evaluating
      the relative effectiveness of two types orthotic devices. There is very limited
      evidence of the effectiveness of therapeutic shoes. Treatment There is very
      limited evidence of the effectiveness of total contact casts in the treatment of
      diabetic foot ulcers. Overall there is a need to measure the effectiveness of the
      range of pressure relieving interventions for the prevention and treatment of
      diabetic foot ulcers as there is a small amount of poor quality research in this
      area.

PMID- 10908551
TI  - Risperidone versus other atypical antipsychotic medication for schizophrenia.
AB  - BACKGROUND: Risperidone is one of a number of 'atypical antipsychotics' which are
      currently being marketed for the treatment of those with schizophrenia, largely
      on the basis of claims of improved tolerability and effectiveness compared to
      much cheaper conventional antipsychotics. The efficacy of risperidone has already
      been compared to conventional drugs, but it remains unclear how risperidone
      compares with other atypical antipsychotic drugs such as clozapine. OBJECTIVES:
      To determine the effects of risperidone compared with other atypical
      antipsychotic drugs for schizophrenia. SEARCH STRATEGY: Electronic searches of
      Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 2000), The
      Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999),
      MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999) and PsycLIT (1974
      1999) were undertaken. In addition, pharmaceutical databases on the Dialog
      Corporation Datastar and Dialog services were searched. References of all
      identified studies were searched for further trials. Pharmaceutical companies and
      authors of trials were contacted. SELECTION CRITERIA: All randomised controlled
      clinical trials that compared risperidone to other atypical antipsychotic
      treatments for schizophrenia and schizophrenia-like psychoses were included by
      independent assessment. DATA COLLECTION AND ANALYSIS: Citations and, where
      possible, abstracts were independently inspected by reviewers, papers ordered, re
      inspected and quality assessed. Data were independently extracted. For
      homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI)
      and, where appropriate, the number needed to treat (NNT) were calculated on an
      intention-to-treat basis. For continuous data, standardised and weighted mean
      differences were calculated (SMD, WMD). All data were inspected for
      heterogeneity. MAIN RESULTS: Nine studies were obtained, comparing risperidone
      with clozapine (five studies - largely amongst treatment resistant patients);
      olanzapine (three studies); and amisulpiride (one study). The research was beset
      by problems of high attrition rates and short term follow up. Clozapine does seem
      equally acceptable to risperidone in the short term (leaving the study early,
      n=466, RR 1. 00 CI 0.73-1.37). For most other outcomes wide confidence intervals
      were obtained, which meant that it was impossible to judge whether the two
      compounds were equally effective, or whether one was in fact superior to the
      other. Olanzapine and risperidone seem broadly similar according to numbers of
      patients responding to treatment (40% reduction in PANSS scores: n=339, RR 1.14,
      CI 0.99-1.32). Olanzapine caused fewer people to leave the study early (n=404, RR
      1. 31 CI 1.06-1.60; NNT 8 CI 4-32) and fewer extrapyramidal side effects (n=339,
      RR 1.67 CI 1.14-2.46; NNH 8 CI 5-33), although comparative doses of risperidone
      were higher than those recommended in practice. In one single study (n=228)
      amisulpiride seemed broadly similar to risperidone in most respects. There were
      no useful data presented relating to service use and costs. Very few data
      relating to quality of life were presented. REVIEWER'S CONCLUSIONS: The
      equivalence of clozapine and risperidone for treatment resistant schizophrenia
      cannot yet be assumed and there seems to be little to chose between risperidone
      and both olanzapine and amisulpiride. The research is limited in many respects,
      and longer term studies measuring clinically important outcomes, including
      service use and quality of life are needed to judge the comparative value of the
      various atypical drugs.

PMID- 10908552
TI  - Early use of inhaled corticosteroids in the emergency department treatment of
      acute asthma.
AB  - BACKGROUND: Systemic corticosteroids therapy is central to the management of
      acute asthma The use of inhaled steroids may also be beneficial in this setting.
      OBJECTIVES: To determine the benefit of ICS for the treatment of patients with
      acute asthma managed in the emergency department (ED). SEARCH STRATEGY:
      Randomised controlled trials (RCTs) were identified from the Cochrane Airways
      Review Group register. Bibliographies from included studies, known reviews, and
      texts also were searched. SELECTION CRITERIA: Only RCTs or quasi-randomised
      trials were eligible for inclusion. Studies were included if patients presented
      with acute asthma to the ED or its equivalent, and were treated with ICS or
      placebo, in addition to standard therapy. Two reviewers independently selected
      potentially relevant articles, and then independently selected articles for
      inclusion. Methodological quality was independently assessed by two reviewers.
      DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers
      if the authors were unable to verify the validity of extracted information.
      Missing data were obtained from the authors or calculated from other data
      presented in the paper. MAIN RESULTS: Seven trials were selected for inclusion,
      but data were not available for one of them. In the six usable rials, (4 adult, 2
      paediatric), a total of 352 patients were studied (179 ICS, 173 non-ICS treated).
      Patients treated with ICS were less likely to be admitted to hospital (OR: 0.30;
      95% CI: 0.16, 0.57). This benefit was confined to patients not receiving
      concomitant systemic steroids. Such patients showed the same, but non
      significant, trend towards reduced admissions compared to placebo treatment (OR
      0.46; 95% CI: 0. 19, 1.11). In children, ICS appeared to be at least as effective
      as systemic steroids (OR 0.5; 95% CI: 0.24, 1.06). Patients receiving ICS
      demonstrated small, significant improvements in peak expiratory flows (PEFR WMD:
      7%; 95% CI: 3, 13) and forced expiratory volumes (FEV-FEV1 WMD: 5.0%; 95% CI:
      0.4, 9.7). The treatment was well tolerated, with few reported adverse side
      effects. REVIEWER'S CONCLUSIONS: Inhaled steroids reduced admission rates in
      patients with acute asthma who were not receiving concomitant systemic steroids.
      In children, inhaled steroids appear to be at least as effective as systemic
      steroids. Further research is needed to clarify the effect of ICS when used in
      addition to systemic corticosteroids, and to determine the optimal dose, agent,
      and frequency of ICS administration.

PMID- 10908553
TI  - Inhaled steroids for neonatal chronic lung disease.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic disorder associated
      with prematurity. Systemic steroids induce at least a temporary improvement in
      respiratory function, but are associated with adverse side effects. Inhaled
      steroids have fewer side effects. OBJECTIVES: To determine if inhaled
      corticosteroids are effective in alleviating the morbidity of bronchopulmonary
      dysplasia (BPD) compared to 0-placebo. SEARCH STRATEGY: We identified randomised,
      controlled trials (RCT) within the Cochrane Database, references from retrieved
      trials, hand searches of journals and contact with pharmaceutical companies and
      experts in this field. SELECTION CRITERIA: Only randomised controlled trials
      involving infants with chronic lung disease of prematurity and treated with
      inhaled steroids versus placebo were included. Patients receiving systemic
      corticosteroids were excluded. Co-interventions included antenatal systemic
      steroids, routine neonatal intensive care, ventilatory support, surfactant
      replacement therapy, diuretics and bronchodilators. DATA COLLECTION AND ANALYSIS:
      Four of the seven included trials were of good methodological quality. There were
      five parallel-group trials in ventilated infants. These were comparable in terms
      of population, co-interventions and need for increased inspired oxygen
      concentration. They differed in terms of type, dose and duration (7-28 days) of
      inhaled steroids. Two cross-over trials were performed in non-ventilated
      patients. MAIN RESULTS: The inability to extubate during treatment was markedly
      reduced in infants treated with inhaled steroids; Peto Odds Ratio (OR) 0.12, 95%
      Confidence Interval (CI) 0.03 to 0.43. There was heterogeneity in this finding,
      however, with one study that contributed 30% of the total number of patients
      reporting no successful extubations in either treatment arm over one week. The
      risk of sepsis appeared similar between the two groups (N=3, OR=0.72, 95%CI: 0.21
      to 2.43). The small number of trials precluded analysis to examine the effect of
      differences in drug, duration of therapy, delivery system, co-interventions, and
      disease severity. Reduced oxygen requirements were reported in one of the two
      trials performed in non-ventilated infants, but inadequate data reporting
      precluded pooling of data. REVIEWER'S CONCLUSIONS: In ventilated infants with
      BPD, inhaled steroids administered for 1 to 4 weeks improved the rate of
      extubation with no apparent increase in the risk of sepsis. No firm conclusion
      could be derived with regard to the efficacy of inhaled steroids in non
      ventilated infants.

PMID- 10908554
TI  - Intra-pleural fibrinolytic therapy vs. conservative management in the treatment
      of parapneumonic effusions and empyema.
AB  - BACKGROUND: Effusions and empyema may complicate lower respiratory tract
      infections. Loculation of fluid is a major problem with this condition so
      treatments have included surgical drainage and the use of intra-pulmonary
      fibrinolysis to break down fibrin bands that may cause loculation. OBJECTIVES: To
      conduct a systematic review of the benefit of adding intrapleural fibrinolytic
      therapy to intercostal tube drainage in the treatment of complicated
      parapneumonic effusions and empyema. SEARCH STRATEGY: The Cochrane Controlled
      Trials Register was initially searched for relevant RCT's. The search terms were
      Streptokinase OR Urokinase AND Pleural Effusion OR Intrapleural OR Pleur* OR
      Parapneumonic Or Empyema. Bibliographies and review articles identified herein
      were searched for further citations and RCT's. MEDLINE, EMBASE were searched and,
      where relevant, Index Medicus was hand searched. Trial authors were contacted for
      further information and details regarding the possibility of unpublished trials
      was requested. SELECTION CRITERIA: Types of Studies All studies in the review
      were Randomised Controlled Trials in adult patients empyema or complicated
      parapneumonic effusions who had not had prior surgical intervention or trauma.
      The intervention was an intrapleural fibrinolytic agent (streptokinase or
      urokinase) vs control or a comparison of the two. DATA COLLECTION AND ANALYSIS:
      All identified studies were reviewed independently by two reviewer and all data
      collected. Reviews were scored according to the Cochrane assessment of allocation
      concealment and the Jadad scale of methodological quality. Disagreements between
      reviewers were referred to a third reviewer. Where further information was
      required, authors of trial papers were contacted for further details. MAIN
      RESULTS: Three studies were identified, one which directly compared the
      fibrinolytics streptokinase and urokinase. Two small RCTs (total 58 patients)
      compared streptokinase or urokinase vs normal saline control. The pooled data
      showed small benefits in terms of hospital stay, time to defervescence,
      improvement in chest radiograph, requirement for surgery, but the results were
      not always consistent across studies. Complications attributable to therapy were
      not seen. REVIEWER'S CONCLUSIONS: There is currently insufficient evidence to
      support routine use of intrapleural fibrinolytic therapy in the treatment of
      parapneumonic effusion and empyema. The results of a large multi-centre study,
      currently underway, are awaited.

PMID- 10908555
TI  - Anti-leukotriene agents compared to inhaled corticosteroids in the management of
      recurrent and/or chronic asthma.
AB  - BACKGROUND: Inhaled corticosteroids are the cornerstone of anti-inflammatory
      asthma treatment. Anti-leukotrienes agents are currently being studied as
      alternative first line agents in the management of mild to moderate chronic
      asthma. OBJECTIVES: The aims of this review study are to compare the safety and
      efficacy of anti-leukotriene agents with inhaled glucocorticoids and to determine
      the dose-equivalence of anti-leukotrienes in mcg of inhaled corticosteroids in
      the management of chronic asthma. SEARCH STRATEGY: The searched Medline (1966 to
      1999), Embase (1980 to 1999), Cinahl (1982 to 1999) and reference lists of review
      articles and trials; we contacted colleagues and international headquarters of
      anti-leukotrienes producers. SELECTION CRITERIA: Randomised controlled trials
      were included if they compared leukotriene antagonists with inhaled
      corticosteroids during a minimal 30-day intervention period in asthmatic patients
      aged 2 years and older, and if measures of effectiveness other than compliance
      were included. DATA COLLECTION AND ANALYSIS: Assessments of methodological
      quality and data extraction were performed independently and blindly by two
      reviewers. The primary outcome was the rate of exacerbations requiring systemic
      corticosteroids. Secondary outcomes included lung function, indices of chronic
      asthma control, adverse effects and withdrawal rates. MAIN RESULTS: Of 137
      identified studies, ten met the inclusion criteria. Two are currently published
      in full-text. Most focused on subjects with mild-to-moderate chronic asthma; two
      included children. Trial duration was 6 to 12 weeks with a few un-blinded trials
      lasting several months. Daily dose of inhaled corticosteroids varied from 250 to
      400 mcg of beclomethasone-equivalent; various anti-leukotriene preparation were
      tested. There was no difference in the rate of patients with exacerbations that
      required systemic steroids [4 trials, Relative Risk (RR)=1.3, (95% Confidence
      Interval (CI): 0.9, 1.9)]. Few trials contributed data to other outcomes.
      Improvement in lung function (FEV1 [N=3 trials, Standardised Mean Difference
      (SMD)=0.3 (95% CI: 0. 2, 0.4)]: morning PEFR [3 trials, SMD=0.4, (95% CI: 0.2,
      0.5)]) and in quality of life [N=3 trials, WMD=0.3, (95% CI: 0.1, 0.4)] favoured
      inhaled corticosteroids. A difference in favour of inhaled corticosteroids was
      observed for symptoms [N=3 trials, SMD=0.3, (95% CI: = 0.2, 0.4)], night
      awakenings [N=2 trials, WMD= 0.6, (95% CI: 0. 3, 0.9)], and rescue beta2-agonists
      [N=3 trials, SMD= 0.3, (95% CI: 0.2, 0.4)] Side effects were not different
      between groups, but anti-leukotriene therapy was associated with increase risk of
      "withdrawals for any cause" [N=3 trials, RR=1.4, (95% CI: 1.1, 1.9)] and
      "withdrawals due to adverse effects" [N=3 trials, RR=1.9, (95% CI: 1.1, 3.3)]
      REVIEWER'S CONCLUSIONS: Anti-leukotriene agents had a similar rate of
      exacerbations compared to inhaled corticosteroids, but inhaled steroids produced
      better lung function and quality of life as well as reduced symptoms, night
      awakenings and need for rescue beta2-agonist. Reliable conclusions cannot yet be
      drawn regarding the efficacy of this treatment due to the paucity of trials
      published in full text.

PMID- 10908556
TI  - Inhaled steroids in acute asthma following emergency department discharge.
AB  - BACKGROUND: Patients with acute asthma treated in the emergency department are
      frequently treated with inhaled beta-agonists and corticosteroids (CS) after
      discharge. The use of inhaled CS (ICS) following discharge may also be beneficial
      in acute asthma. OBJECTIVES: To determine the effect of inhaled corticosteroids
      (ICS) on outcomes in the treatment of acute asthma following discharge from the
      emergency department (ED). SEARCH STRATEGY: Randomised controlled trials (RCTs)
      were identified from the Cochrane Airways Review Group register which consists of
      systematic searches of EMBASE, MEDLINE and CINAHL databases supplemented by hand
      searching of 20 respiratory journals. In addition, abstracts from conferences
      were searched; primary authors and pharmaceutical companies were contacted to
      identify eligible studies. Bibliographies from included studies, known reviews,
      and texts also were searched. SELECTION CRITERIA: Only RCTs or quasi RCTs were
      eligible for inclusion. Studies were included if patients were treated for acute
      asthma in the ED or its equivalent, and following ED discharge were treated with
      ICS therapy either in addition to, or as a substitute for, oral corticosteroids
      (CS). Two reviewers independently assessed articles for potential relevance,
      final inclusion, and methodological quality - to "expand" the search. We didn't
      include any in the end) DATA COLLECTION AND ANALYSIS: Data were extracted
      independently by two reviewers if the authors were unable to verify the validity
      of information. Several authors and pharmaceutical companies provided unpublished
      data. The data were analysed using the Cochrane Review Manager 4.0.4. MAIN
      RESULTS: Ten trials were selected for inclusion. Three of these trials, involving
      a total of 909 patients, compared ICS plus CS Vs CS therapy alone. There was no
      demonstrated benefit of ICS therapy when used in addition to CS therapy in the
      trials. Relapses were reduced, but not significantly, with the addition of ICS
      therapy (OR: 0.68; 95% CI: 0.46 to 1.02). As well, no differences were
      demonstrated between the two groups for relapses requiring admission, quality of
      life, symptom scores, or adverse effects. Seven trials, involving a total of 1204
      patients, compared high-dose ICS therapy alone Vs CS therapy alone after ED
      discharge. There were no significant differences demonstrated between ICS therapy
      alone and CS therapy alone for relapse rates (OR: 1.00; 95% CI: 0.66 to 1.52) or
      in the secondary outcomes of beta-agonist use, symptoms, or adverse events.
      However, the sample size was not adequate to confidently exclude the possibility
      of either treatment being significantly inferior, and severe asthmatics were
      excluded from these trials. REVIEWER'S CONCLUSIONS: There is insufficient
      evidence that ICS therapy provides additional benefit when used in combination
      with standard CS therapy upon ED discharge for acute asthma. There is some
      evidence that high-dose ICS therapy alone may be as effective as CS therapy when
      used in mild asthmatics upon ED discharge; however, there is a significant
      possibility of a type II error in drawing this conclusion. Further research is
      needed to clarify whether ICS therapy should be employed in acute asthma
      treatment in the ED or following ED discharge.

PMID- 10908557
TI  - Tricyclic drugs for depression in children and adolescents.
AB  - BACKGROUND: There is a need to identify effective and safe treatments for
      depression in children and adolescents. While tricyclic drugs have proven
      effectiveness in the treatment of depression in adults, individual studies
      involving children and adolescent have been equivocal. OBJECTIVES: To examine
      whether orally administered tricyclic antidepressants are superior to placebo in
      the treatment of child and adolescent depression SEARCH STRATEGY: We searched the
      literature using CD ROM Silver Platter and On-Line MEDLINE (1966-1997) and
      Excerpta Medica (June 1974-1997) data bases. Terms used for the search were: the
      exploded terms child and depression; the Medical Subject Headings of
      antidepressant drugs, tricyclic and affective disorders; individual tricyclic
      drugs by name; names of well-known researchers in the field; and school phobia.
      We searched the trials database of the Cochrane Collaboration Depression, Anxiety
      and Neurosis Group. Abstracts in English (of English and non-English papers) were
      reviewed. Bibliographies of previously published reviews and papers describing
      original research were cross-checked. Current Contents was screened for recent
      publications. We contacted authors of abstracts describing "work in progress"
      identified in conference proceedings of the American Academy of Child and
      Adolescent Psychiatry to determine whether they held data which could be included
      in the meta-analysis. We have hand searched the Journal of the American Academy
      of Child and Adolescent Psychiatry to identify randomized controlled trials.
      SELECTION CRITERIA: Randomized controlled trials comparing the efficacy of orally
      administered tricyclic medication with placebo in depressed subjects aged 6-18
      years. DATA COLLECTION AND ANALYSIS: Most studies reported multiple outcome
      measures including depression scales and clinical global impression scales. For
      each study the best available depression measure was taken as the index measure
      of depression outcome. Predetermined criteria were established to assist in the
      ranking of measures. Where authors reported categorical outcomes we calculated
      individual and pooled odds ratios for the odds of improvement in treated compared
      with control subjects. For continuous outcomes pooled effect sizes were
      calculated as the number of standard deviations by which the change in depression
      scores for the treatment group exceeded those for the control groups. MAIN
      RESULTS: Twelve studies fulfilled the criteria for inclusion in the review, eight
      from which dichotomous outcome data could be extracted, and eleven from which
      continuous outcome data could be extracted. Pooled odds ratios calculated from
      the dichotomous data indicated no advantage of treatment over placebo for
      children or adolescents (odds ratio = 0.83, 95% confidence interval 0.48 to
      1.42). Effect size calculations from the continuous data suggested a
      statistically significant but small benefit of treatment over placebo in reducing
      symptoms for the aggregate sample (effect size = -0.38, 95% confidence interval 
      0.74 to -0.02) with subgroup analyses suggesting a larger benefit among
      adolescents (effect size = -0.59, 95% confidence interval -1.12 to -0.06), and no
      benefit among children (effect size = 0.15, 95% confidence interval -0.34 to
      0.64). Treatment with a tricyclic antidepressant caused more vertigo (odds ratio
      = 8.47, 95% confidence interval 1.40 to 51.0), orthostatic hypotension (odds
      ratio = 4.77, 95% confidence interval 1.11 to 20.49) and dry mouth (odds ratio =
      5.19, 95% confidence interval 1.15 to 23.51) than did placebo, but there was no
      statistically significant difference in other possible adverse effects.
      REVIEWER'S CONCLUSIONS: Data suggest tricyclic antidepressants are of unlikely
      benefit in the treatment of depression in pre pubertal children. There is
      marginal evidence to support the use of tricyclic antidepressants in the
      treatment of depression in adolescents, although the magnitude of effect is
      likely to be moderate at best.

PMID- 10908558
TI  - Carbamazepine versus valproate monotherapy for epilepsy.
AB  - BACKGROUND: Carbamazepine and valproate are drugs of first choice for epilepsy.
      Despite the lack of hard evidence from individual randomized controlled trials,
      there is strong clinical belief that valproate is the drug of choice for
      generalized epilepsies and carbamazepine for partial epilepsies. OBJECTIVES: To
      overview the best evidence comparing carbamazepine and valproate monotherapy
      SEARCH STRATEGY: Our search strategy included: (a) MEDLINE 1966-99, (b) The
      Cochrane Library 1999 issue 4, (c) The trial register of the Cochrane Epilepsy
      Group (d) the pharmaceutical industry. SELECTION CRITERIA: Randomized controlled
      trials comparing carbamazepine and valproate monotherapy for epilepsy. DATA
      COLLECTION AND ANALYSIS: This was an individual patient data review. Outcome
      measures were time to withdrawal of allocated treatment, time to 12 month
      remission, and time to first seizure post randomization. Data were analysed using
      the stratified Logrank test with results expressed as hazard ratios (HR) (95%
      CI), where HR>1 indicates an event is more likely on valproate. A test for an
      interaction between treatment and epilepsy type (partial versus generalized) was
      also undertaken. MAIN RESULTS: Results Data were available for 1265 patients from
      five trials, representing 85% of the patients recruited into the eight trials
      that met our inclusion criteria. The main overall results (HR 95% CI) were: Time
      to treatment withdrawal 0.97 (0.79-1.18), 12 month remission 0.87 (0.74-1.02),
      first seizure 1.09 (0.96-1.25) suggesting no overall difference for these
      outcomes. The test for an interaction between treatment and epilepsy type was non
      significant for time to treatment withdrawal and 12 month remission, but
      significant for time to first seizure. The age distribution of adults classified
      as having a generalized epilepsy indicate that significant numbers of patients
      may have had their epilepsy misclassified. REVIEWER'S CONCLUSIONS: We have found
      some evidence to support the policy of using carbamazepine as the first treatment
      of choice in partial epilepsies, but no evidence to support the choice of
      valproate in generalized epilepsies, but confidence intervals are too wide to
      confirm equivalence. Misclassification of patients may have confounded our
      results, and has important implications for the design and conduct of future
      trials.

PMID- 10908559
TI  - Id-1 delays senescence but does not immortalize keratinocytes.
AB  - Defining the molecular basis responsible for regulating the proliferative
      potential of keratinocytes has important implications for normal homeostasis and
      neoplasia of the skin. Under current culture conditions, neonatal foreskin
      derived human keratinocytes possess a relatively short replicative lifespan.
      Recently it was reported that forced overexpression of the helix-loop-helix
      protein Id-1 was capable of immortalizing keratinocytes, secondary to activation
      of telomerase activity and suppression of p16/Rb-mediated growth arrest pathways.
      To investigate the relationship between Id-1, telomerase activity, telomere
      length, p16, Rb cell cycle regulators, and senescence, whole populations of
      keratinocytes were infected with a retrovirus to induce overexpression of Id-1.
      In these unselected cultures, enhanced Id-1 levels clearly extended the lifespan
      of keratinocytes, but Id-1 did not prevent the onset of replicative senescence.
      Under these experimental conditions, Id-1 expression did not trigger induction of
      telomerase activity, and there was progressive shortening of the telomeres that
      was accompanied by elevated p16 levels and prevalence of active Rb. The ability
      of Id-1 to postpone, but not prevent, senescence may be related to partial
      inhibition of p16 expression, as the Id-1-overexpressing cultures displayed a
      decreased capacity for 12-O-tetradecanoylphorbol-13-acetate-mediated p16
      induction. Thus, while no immortalization was observed, Id-1 could delay the
      onset of replicative senescence in unselected human keratinocyte populations.

PMID- 10908560
TI  - The chromosomal protein sso7d of the crenarchaeon Sulfolobus solfataricus rescues
      aggregated proteins in an ATP hydrolysis-dependent manner.
AB  - In this work, we show that the nonspecific DNA-binding protein Sso7d from the
      crenarchaeon Sulfolobus solfataricus displays a cation-dependent ATPase activity
      with a pH optimum around neutrality and a temperature optimum of 70 degrees C.
      Measurements of tryptophan fluorescence and experiments that used 1
      anilinonaphthalene-8-sulfonic acid as probe demonstrated that ATP hydrolysis
      induces a conformational change in the molecule and that the binding of the
      nucleotide triggers the ATP hydrolysis-induced conformation of the protein to
      return to the native conformation. We found that Sso7d rescues previously
      aggregated proteins in an ATP hydrolysis-dependent manner; the native
      conformation of Sso7d forms a complex with the aggregates, while the ATP
      hydrolysis-induced conformation is incapable of this interaction. Sso7d is
      believed to be the first protein isolated from an archaeon capable of rescuing
      aggregates.

PMID- 10908561
TI  - Identification and characterization of a novel factor that regulates quinone
      reductase gene transcriptional activity.
AB  - The regulation of the quinone reductase (QR) gene as well as other genes involved
      in detoxification is known to be mediated by an electrophile/antioxidant response
      element (EpRE/ARE). We have previously observed that QR is up-regulated by the
      antiestrogen trans-hydroxytamoxifen in breast cancer cells. QR gene regulation by
      the antiestrogen-occupied estrogen receptor (ER) is mediated by the EpRE
      containing region of the human QR gene, and the ER is one of the complex of
      proteins that binds to the EpRE. In an effort to further understand the mechanism
      for ER regulation of QR gene we identified other protein factors that regulate QR
      gene transcriptional activity in breast cancer cells. One of these protein
      factors, hPMC2 (human homolog of Xenopus gene which prevents mitotic
      catastrophe), directly binds to the EpRE and interacts with the ER in yeast
      genetic screening and in vitro assays. Interestingly hPMC2 interacts more
      strongly to ER beta when compared with ER alpha. In transient transfection assays
      using reporter constructs containing the EpRE, hPMC2 alone can slightly activate
      reporter in ER-negative MDA-MB-231 breast cancer cells. The activation of QR gene
      activity by hPMC2 is enhanced in the presence of ER beta.

PMID- 10908562
TI  - Functional constraints of nuclear-mitochondrial DNA interactions in
      xenomitochondrial rodent cell lines.
AB  - The co-evolution of nuclear and mitochondrial genomes in vertebrates led to more
      than 100 specific interactions that are crucial for an optimized ATP generation.
      These interactions have been examined by introducing rat mtDNA into mouse cells
      devoid of mitochondrial DNA (mtDNA). When mtDNA-less cells derived from the
      common mouse (Mus musculus domesticus) were fused to cytoplasts prepared from Mus
      musculus, Mus spretus, or rat (Rattus norvegicus), a comparable number of
      respiring clones could be obtained. Mouse xenomitochondrial cybrids harboring rat
      mtDNA had a slower growth rate in medium containing galactose as the carbon
      source, suggesting a defect in oxidative phosphorylation. These clones respired
      approximately 50% less than the parental mouse cells or xenomitochondrial cybrids
      harboring Mus spretus mtDNA. The activities of respiratory complexes I and IV
      were approximately 50% lower, but mitochondrial protein synthesis was unaffected.
      The defects in complexes I and IV were associated with decreased steady-state
      levels of respective subunits suggesting problems in assembly. We also showed
      that the presence of 10% mouse mtDNA co-existing with rat mtDNA was sufficient to
      restore respiration to normal levels. Our results suggest that evolutionary
      distance alone is not a precise predictor of nuclear-mitochondrial interactions
      as previously suggested for primates.

PMID- 10908563
TI  - Expression of Rattus norvegicus mtDNA in Mus musculus cells results in multiple
      respiratory chain defects.
AB  - The production of in vitro and in vivo models of mitochondrial DNA (mtDNA)
      defects is currently limited by a lack of characterized mouse cell mtDNA mutants
      that may be expected to model human mitochondrial diseases. Here we describe the
      creation of transmitochondrial mouse (Mus musculus) cells repopulated with mtDNA
      from different murid species (xenomitochondrial cybrids). The closely related Mus
      spretus mtDNA is readily maintained when introduced into M. musculus mtDNA-less
      (rho(0)) cells, and the resulting cybrids have normal oxidative phosphorylation
      (OXPHOS). When the more distantly related Rattus norvegicus mtDNA is transferred
      to the mouse nuclear background the mtDNA is replicated, transcribed, and
      translated efficiently. However, function of several OXPHOS complexes that depend
      on the coordinated assembly of nuclear and mtDNA-encoded proteins is impaired.
      Complex I activity in the Rattus xenocybrid was 46% of the control mean; complex
      III was 37%, and complex IV was 78%. These defects combined to restrict maximal
      respiration to 12-31% of the control and M. spretus xenocybrids, as measured
      polarographically using isolated cybrid mitochondria. These defects are distinct
      to those previously reported for human/primate xenocybrids. It should be possible
      to produce other mouse xenocybrid constructs with less severe OXPHOS phenotypes,
      to model human mtDNA diseases.

PMID- 10908564
TI  - Akt/protein kinase B isoforms are differentially regulated by epidermal growth
      factor stimulation.
AB  - Overexpression of epidermal growth factor receptor (EGFR) in certain cancers is
      well established. There is growing evidence that epidermal growth factor (EGF)
      activates Akt/protein kinase B (PKB) in a phosphoinositide 3-OH kinase (PI3K)
      dependent manner, but it is not yet clear which Akt isoforms are involved in this
      signal transduction pathway. We investigated the functional regulation of three
      Akt isoforms, Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma, in esophageal
      cancer cells where EGFR is frequently overexpressed. Upon EGF simulation,
      phosphorylation of Akt1 at the Ser-473 residue was remarkably induced. This
      result was corroborated by in vitro Akt kinase assays using glycogen synthase
      kinase 3beta as the substrate. PI3K inhibitors, wortmannin or LY294002,
      significantly blocked the Akt kinase activity induced by EGF. Akt2 activity was
      evaluated by electrophoretic mobility shift assays. Robust activation of Akt2 by
      EGF was observed in some cell lines in a PI3K-dependent manner. EGF-induced Akt3
      activation was demonstrated by Ser-472 phosphorylation of Akt3 but in a
      restrictive fashion. In aggregate, EGF-mediated activation of Akt isoforms is
      overlapping and distinctive. The mechanism by which EGFR recruits the PI3K/Akt
      pathway was in part differentially regulated at the level of Ras but independent
      of heterodimerization of EGFR with either ErbB2 or ErbB3 based upon functional
      dissection of pathways in esophageal cancer cell lines.

PMID- 10908565
TI  - Chemical analysis of the developmental pattern of polysialylation in chicken
      brain. Expression of only an extended form of polysialyl chains during
      embryogenesis and the presence of disialyl residues in both embryonic and adult
      chicken brains.
AB  - Recent studies have demonstrated the involvement of two polysialyltransferases in
      neural cell adhesion molecule (N-CAM) polysialylation. The availability of cDNAs
      encoding these enzymes facilitated studies on polysialylation of N-CAM. However,
      there is a dearth of detailed structural information on the degree of
      polymerization (DP), DP ranges, and the influence of embryogenesis on the DP. It
      is also unclear how many polysialic acid (polySia) chains are attached to a
      single core N-glycan. In this paper we applied new, efficient, and sensitive high
      pressure liquid chromatography methods to qualitatively and quantitatively
      analyze the polySia structures expressed on embryonic and adult chicken brain N
      CAM. Our studies resulted in the following new findings. 1) The DP of the polySia
      chains was invariably 40-50 throughout developmental stages from embryonic day 5
      to 21 after fertilization. In contrast, glycopeptides containing polySia with
      shorter DPs, ranging from 15 to 35, were isolated from adult brain. 2) Chemical
      evidence showed glycan chains abundant in Neu5Acalpha2,8Neu5Ac were expressed
      during all developmental stages including adult. 3) Levels of both di- and
      polySia were found to show distinctive changes during embryonic development.

PMID- 10908566
TI  - Identification of essential amino acid residues in the Sinorhizobium meliloti
      glucosyltransferase ExoM.
AB  - ExoM is a beta(1-4)-glucosyltransferase involved in the assembly of the repeat
      unit of the exopolysaccharide succinoglycan from Sinorhizobium meliloti. By
      comparing the sequence of ExoM to those of other members of the Pfam Glyco Domain
      2 family, most notably SpsA (Bacillus subtilis) for whom the three-dimensional
      structure has been resolved, three potentially important aspartic acid residues
      of ExoM were identified. Single substitutions of each of the Asp amino acids at
      positions 44, 96, and 187 with Ala resulted in the loss of mutant recombinant
      protein activity in vitro as well as the loss of succinoglycan production in an
      in vivo rescue assay. Mutants harboring Glu instead of Asp-44 or Asp-96 possessed
      no in vitro activity but could restore succinoglycan production in vivo. However,
      replacement of Asp-187 with Glu completely inactivated ExoM as judged by both the
      in vitro and in vivo assays. These results indicate that Asp-44, Asp-96, and Asp
      187 are essential for the activity of ExoM. Furthermore, these data are
      consistent with the functions proposed for each of the analogous aspartic acids
      of SpsA based on the SpsA-UDP structure, namely, that Asp-44 and Asp-96 are
      involved in UDP substrate binding and that Asp-187 is the catalytic base in the
      glycosyltransferase reaction.

PMID- 10908567
TI  - Identification of an essential amino acid motif within the C terminus of the
      pituitary adenylate cyclase-activating polypeptide type I receptor that is
      critical for signal transduction but not for receptor internalization.
AB  - The pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 (PAC1)
      receptor is a G protein-coupled receptor and class II receptor member. The
      receptor domains critical for signaling are unknown. To explore the role of the C
      terminus, truncations of 63 residues (Tr406), 53 residues (Tr416), 49 residues
      (Tr420), 44 residues (Tr424), and 37 residues (Tr433) were constructed and
      expressed in NIH/3T3 cells, and immunofluorescence, radioligand binding, adenylyl
      cyclase (AC) and phospholipase C (PLC) assays were performed. (125)I-PACAP-27
      binding (K(d) = 0.6-1.5 nm) for the Tr406 and Tr433 were similar to wild type Hop
      and Null splice variants (K(d) = approximately 1.1 nm). Although internalization
      of ligand for both the Tr406 and Tr433 mutants was reduced to 50-60% at 60 min
      compared with 76-87% for WT, loss of G protein coupling did not account for
      differences in internalization. Despite similar binding properties Tr406 and
      Tr416 mutants showed no AC or PLC response. Addition of 14 amino acids distal to
      HopTr406 resulted in normal AC and PLC responses. Site-directed mutagenesis
      indicated that Arg(416) and Ser(417) are essential for G protein activation. The
      proximal C terminus mediates signal transduction, and the distal is involved with
      internalization. Two residues within the C terminus, Arg(416) and Ser(417)
      conserved among class II receptors are the likely sites for G protein coupling.

PMID- 10908568
TI  - G protein-coupled receptor-induced sensitization of phospholipase C stimulation
      by receptor tyrosine kinases.
AB  - Activation of stably expressed M(2) and M(3) muscarinic acetylcholine receptors
      (mAChRs) as well as of endogenously expressed lysophosphatidic acid and
      purinergic receptors in HEK-293 cells can induce a long lasting potentiation of
      phospholipase C (PLC) stimulation by these and other G protein-coupled receptors
      (GPCRs). Here, we report that GPCRs can induce an up-regulation of PLC
      stimulation by receptor tyrosine kinases (RTKs) as well and provide essential
      mechanistic characteristics of this sensitization process. Pretreatment of HEK
      293 cells for 2 min with carbachol, a mAChR agonist, lysophosphatidic acid, or
      ATP, followed by agonist washout, strongly increased (by 2-3-fold) maximal PLC
      stimulation (measured >/=40 min later) by epidermal growth factor and platelet
      derived growth factor, but not insulin, and largely enhanced PLC sensitivity to
      these RTK agonists. The up-regulation of RTK-induced PLC stimulation was
      cycloheximide-insensitive and was observed for up to approximately 90 min after
      removal of the GPCR agonist. Sensitization of receptor-induced PLC stimulation
      caused by prior M(2) mAChR activation was fully prevented by pertussis toxin and
      strongly reduced by expression of Gbetagamma scavengers. Furthermore, inhibition
      of conventional protein kinase C (PKC) isoenzymes and chelation of intracellular
      Ca(2+) suppressed the sensitization process, while overexpression of PKC-alpha,
      but not PKC-betaI, further enhanced the M(2) mAChR-induced sensitization of PLC
      stimulation. None of these treatments affected acute PLC stimulation by either
      GPCR or RTK agonists. Taken together, short term activation of GPCRs can induce a
      strong and long lasting sensitization of PLC stimulation by RTKs, a process
      apparently involving G(i)-derived Gbetagammas as well as increases in
      intracellular Ca(2+) and activation of a PKC isoenzyme, most likely PKC-alpha.

PMID- 10908569
TI  - The use of enzyme therapy to regulate the metabolic and phenotypic consequences
      of adenosine deaminase deficiency in mice. Differential impact on pulmonary and
      immunologic abnormalities.
AB  - Adenosine deaminase (ADA) deficiency results in a combined immunodeficiency
      brought about by the immunotoxic properties of elevated ADA substrates.
      Additional non-lymphoid abnormalities are associated with ADA deficiency,
      however, little is known about how these relate to the metabolic consequences of
      ADA deficiency. ADA-deficient mice develop a combined immunodeficiency as well as
      severe pulmonary insufficiency. ADA enzyme therapy was used to examine the
      relative impact of ADA substrate elevations on these phenotypes. A "low-dose"
      enzyme therapy protocol prevented the pulmonary phenotype seen in ADA-deficient
      mice, but did little to improve their immune status. This treatment protocol
      reduced metabolic disturbances in the circulation and lung, but not in the thymus
      and spleen. A "high-dose" enzyme therapy protocol resulted in decreased metabolic
      disturbances in the thymus and spleen and was associated with improvement in
      immune status. These findings suggest that the pulmonary and immune phenotypes
      are separable and are related to the severity of metabolic disturbances in these
      tissues. This model will be useful in examining the efficacy of ADA enzyme
      therapy and studying the mechanisms underlying the immunodeficiency and pulmonary
      phenotypes associated with ADA deficiency.

PMID- 10908570
TI  - CD43-mediated signals induce DNA binding activity of AP-1, NF-AT, and NFkappa B
      transcription factors in human T lymphocytes.
AB  - Although numerous reports document a role for CD43 in T cell signaling, the
      direct participation of this molecule in cell activation has been questioned. In
      this study we show that CD43 ligation on human normal peripheral T cells was
      sufficient to induce interleukin-2, CD69, and CD40-L gene expression, without
      requiring signals provided by additional receptor molecules. This response was
      partially inhibited by cyclosporin A and staurosporine, suggesting the
      participation of both the Ca(2+) and the protein kinase C pathways in CD43
      signaling. Consistent with the transient CD43-dependent intracellular Ca(2+)
      peaks reported by others, signals generated through the CD43 molecule resulted in
      the induction of NF-AT DNA binding activity. CD43-dependent signals resulted also
      in AP-1 and NFkappaB activation, probably as a result of protein kinase C
      involvement. AP-1 complexes bound to the AP-1 sequence contained c-Jun, and those
      bound to the NF-AT-AP-1 composite site contained c-Jun and Fos. NFkappaB
      complexes containing p65 could be found as early as 1 h after CD43 cross-linking,
      suggesting that CD43 participates in early events of T cell activation. The
      induction of the interleukin-2, CD69, and CD-40L genes and the participation of
      AP-1, NF-AT, and NFkappaB in the CD43-mediated signaling cascade implicate an
      important role for this molecule in the regulation of gene expression and cell
      function.

PMID- 10908571
TI  - Evidence that the serum inhibitor of hyaluronidase may be a member of the inter
      alpha-inhibitor family.
AB  - A study of the uncharacterized serum inhibitors of hyaluronidase, first described
      half a century ago, was undertaken. Activity was measured against bovine
      testicular hyaluronidase using a microtiter-based assay and reverse hyaluronan
      substrate gel zymography. The predominant inhibitory activity was magnesium
      dependent and could be eliminated by protease or chondroitinase digestion and by
      heat treatment. Kinetics of inhibition were similar against hyaluronidases from
      testis and snake and bee venoms. The inhibitor had no effect on Streptomyces
      hyaluronidase, indicating that inhibition was not through protection of the
      hyaluronan substrate. Inhibition levels in serum were increased in mice following
      carbon tetrachloride or interleukin-1 injection, inducers of the acute-phase
      response. Reverse zymography identified a predominant band of 120-kDa relative
      molecular size, with two bands of greater and one of smaller size. The
      predominant protein was tentatively identified as a member of the inter-alpha
      inhibitor family. Inhibition was also observed using either purified inter-alpha
      inhibitor or an inter-alpha-inhibitor-related 120-kDa complex. Inter-alpha
      inhibitor, found in the hyaluronan-rich cumulus mass surrounding mammalian ova
      and the coat of fibroblasts and mesothelial cells, may function to stabilize such
      matrices by protecting against hyaluronidase degradation. Turnover of circulating
      hyaluronan is extraordinarily rapid, with a half-life of 2-5 min. Prompt
      increases in levels of serum hyaluronan occur in patients with shock, septicemia,
      or massive burns, increases that can be attributed, in part, to suppression of
      degradation by these acute-phase reactants, the inhibitors of hyaluronidase.

PMID- 10908572
TI  - Rad51 accumulation at sites of DNA damage and in postreplicative chromatin.
AB  - Rad51, a eukaryotic RecA homologue, plays a central role in homologous
      recombinational repair of DNA double-strand breaks (DSBs) in yeast and is
      conserved from yeast to human. Rad51 shows punctuate nuclear localization in
      human cells, called Rad51 foci, typically during the S phase (Tashiro, S., N.
      Kotomura, A. Shinohara, K. Tanaka, K. Ueda, and N. Kamada. 1996. Oncogene.
      12:2165-2170). However, the topological relationships that exist in human S phase
      nuclei between Rad51 foci and damaged chromatin have not been studied thus far.
      Here, we report on ultraviolet microirradiation experiments of small nuclear
      areas and on whole cell ultraviolet C (UVC) irradiation experiments performed
      with a human fibroblast cell line. Before UV irradiation, nuclear DNA was
      sensitized by the incorporation of halogenated thymidine analogues. These
      experiments demonstrate the redistribution of Rad51 to the selectively damaged,
      labeled chromatin. Rad51 recruitment takes place from Rad51 foci scattered
      throughout the nucleus of nonirradiated cells in S phase. We also demonstrate the
      preferential association of Rad51 foci with postreplicative chromatin in contrast
      to replicating chromatin using a double labeling procedure with halogenated
      thymidine analogues. This finding supports a role of Rad51 in recombinational
      repair processes of DNA damage present in postreplicative chromatin.

PMID- 10908573
TI  - A fast signal-induced activation of Poly(ADP-ribose) polymerase: a novel
      downstream target of phospholipase c.
AB  - We present the first evidence for a fast activation of the nuclear protein
      poly(ADP-ribose) polymerase (PARP) by signals evoked in the cell membrane,
      constituting a novel mode of signaling to the cell nucleus. PARP, an abundant,
      highly conserved, chromatin-bound protein found only in eukaryotes, exclusively
      catalyzes polyADP-ribosylation of DNA-binding proteins, thereby modulating their
      activity. Activation of PARP, reportedly induced by formation of DNA breaks, is
      involved in DNA transcription, replication, and repair. Our findings demonstrate
      an alternative mechanism: a fast activation of PARP, evoked by inositol 1,4,5,
      trisphosphate-Ca(2+) mobilization, that does not involve DNA breaks. These
      findings identify PARP as a novel downstream target of phospholipase C, and
      unveil a novel fast signal-induced modification of DNA-binding proteins by
      polyADP-ribosylation.

PMID- 10908574
TI  - The acute myeloid leukemia-associated protein, DEK, forms a splicing-dependent
      interaction with exon-product complexes.
AB  - DEK is an approximately 45-kD phosphoprotein that is fused to the nucleoporin CAN
      as a result of a (6;9) chromosomal translocation in a subset of acute myeloid
      leukemias (AMLs). It has also been identified as an autoimmune antigen in
      juvenile rheumatoid arthritis and other rheumatic diseases. Despite the
      association of DEK with several human diseases, its function is not known. In
      this study, we demonstrate that DEK, together with SR proteins, associates with
      the SRm160 splicing coactivator in vitro. DEK is recruited to splicing factor
      containing nuclear speckles upon concentration of SRm160 in these structures,
      indicating that DEK and SRm160 associate in vivo. We further demonstrate that DEK
      associates with splicing complexes through interactions mediated by SR proteins.
      Significantly, DEK remains bound to the exon-product RNA after splicing, and this
      association requires the prior formation of a spliceosome. Thus, DEK is a
      candidate factor for controlling postsplicing steps in gene expression that are
      influenced by the prior removal of an intron from pre-mRNA.

PMID- 10908575
TI  - Determinants of the nuclear localization of the heterodimeric DNA fragmentation
      factor (ICAD/CAD).
AB  - Programmed cell death or apoptosis leads to the activation of the caspase
      activated DNase (CAD), which degrades chromosomal DNA into nucleosomal fragments.
      Biochemical studies revealed that CAD forms an inactive heterodimer with the
      inhibitor of caspase-activated DNase (ICAD), or its alternatively spliced
      variant, ICAD-S, in the cytoplasm. It was initially proposed that proteolytic
      cleavage of ICAD by activated caspases causes the dissociation of the ICAD/CAD
      heterodimer and the translocation of active CAD into the nucleus in apoptotic
      cells. Here, we show that endogenous and heterologously expressed ICAD and CAD
      reside predominantly in the nucleus in nonapoptotic cells. Deletional mutagenesis
      and GFP fusion proteins identified a bipartite nuclear localization signal (NLS)
      in ICAD and verified the function of the NLS in CAD. The two NLSs have an
      additive effect on the nuclear targeting of the CAD-ICAD complex, whereas ICAD-S,
      lacking its NLS, appears to have a modulatory role in the nuclear localization of
      CAD. Staurosporine-induced apoptosis evoked the proteolysis and disappearance of
      endogenous and exogenous ICAD from the nuclei of HeLa cells, as monitored by
      immunoblotting and immunofluorescence microscopy. Similar phenomenon was observed
      in the caspase-3-deficient MCF7 cells upon expressing procaspase-3 transiently.
      We conclude that a complex mechanism, involving the recognition of the NLSs of
      both ICAD and CAD, accounts for the constitutive accumulation of CAD/ICAD in the
      nucleus, where caspase-3-dependent regulation of CAD activity takes place.

PMID- 10908576
TI  - p38 MAP kinase mediates bax translocation in nitric oxide-induced apoptosis in
      neurons.
AB  - Nitric oxide is a chemical messenger implicated in neuronal damage associated
      with ischemia, neurodegenerative disease, and excitotoxicity. Excitotoxic injury
      leads to increased NO formation, as well as stimulation of the p38 mitogen
      activated protein (MAP) kinase in neurons. In the present study, we determined if
      NO-induced cell death in neurons was dependent on p38 MAP kinase activity. Sodium
      nitroprusside (SNP), an NO donor, elevated caspase activity and induced death in
      human SH-SY5Y neuroblastoma cells and primary cultures of cortical neurons.
      Concomitant treatment with SB203580, a p38 MAP kinase inhibitor, diminished
      caspase induction and protected SH-SY5Y cells and primary cultures of cortical
      neurons from NO-induced cell death, whereas the caspase inhibitor zVAD-fmk did
      not provide significant protection. A role for p38 MAP kinase was further
      substantiated by the observation that SB203580 blocked translocation of the cell
      death activator, Bax, from the cytosol to the mitochondria after treatment with
      SNP. Moreover, expressing a constitutively active form of MKK3, a direct
      activator of p38 MAP kinase promoted Bax translocation and cell death in the
      absence of SNP. Bax-deficient cortical neurons were resistant to SNP, further
      demonstrating the necessity of Bax in this mode of cell death. These results
      demonstrate that p38 MAP kinase activity plays a critical role in NO-mediated
      cell death in neurons by stimulating Bax translocation to the mitochondria,
      thereby activating the cell death pathway.

PMID- 10908577
TI  - HIV-1 rev depolymerizes microtubules to form stable bilayered rings.
AB  - We describe a novel interaction between HIV-1 Rev and microtubules (MTs) that
      results in the formation of bilayered rings that are 44-49 nm in external
      diameter, 3.4-4.2 MD (megadaltons) in mass, and have 28-, 30-, or 32-fold
      symmetry. Ring formation is not sensitive to taxol, colchicine, or microtubule
      associated proteins, but requires Mg(2+) and is inhibited by maytansine. The
      interaction involves the NH(2)-terminal domain of Rev and the face of tubulin
      exposed on the exterior of the MTs. The NH(2)-terminal half of Rev has unexpected
      sequence similarity to the tubulin-binding portion of the catalytic/motor domains
      of the microtubule-destabilizing Kin I kinesins. We propose a model wherein
      binding of Rev dimers to MTs at their ends causes segments of two neighboring
      protofilaments to peel off and close into rings, circumferentially containing 14,
      15, or 16 tubulin heterodimers, with Rev bound on the inside. Rev has a strong
      inhibitory effect on aster formation in Xenopus egg extracts, demonstrating that
      it can interact with tubulin in the presence of normal levels of cellular
      constituents. These results suggest that Rev may interact with MTs to induce
      their destabilization, a proposition consistent with the previously described
      disruption of MTs after HIV-1 infection.

PMID- 10908578
TI  - Microtubules remodel actomyosin networks in Xenopus egg extracts via two
      mechanisms of F-actin transport.
AB  - Interactions between microtubules and filamentous actin (F-actin) are crucial for
      many cellular processes, including cell locomotion and cytokinesis, but are
      poorly understood. To define the basic principles governing microtubule/F-actin
      interactions, we used dual-wavelength digital fluorescence and fluorescent
      speckle microscopy to analyze microtubules and F-actin labeled with spectrally
      distinct fluorophores in interphase Xenopus egg extracts. In the absence of
      microtubules, networks of F-actin bundles zippered together or exhibited
      serpentine gliding along the coverslip. When microtubules were nucleated from
      Xenopus sperm centrosomes, they were released and translocated away from the
      aster center. In the presence of microtubules, F-actin exhibited two distinct,
      microtubule-dependent motilities: rapid ( approximately 250-300 nm/s) jerking and
      slow ( approximately 50 nm/s), straight gliding. Microtubules remodeled the F
      actin network, as F-actin jerking caused centrifugal clearing of F-actin from
      around aster centers. F-actin jerking occurred when F-actin bound to motile
      microtubules powered by cytoplasmic dynein. F-actin straight gliding occurred
      when F-actin bundles translocated along the microtubule lattice. These
      interactions required Xenopus cytosolic factors. Localization of myosin-II to F
      actin suggested it may power F-actin zippering, while localization of myosin-V on
      microtubules suggested it could mediate interactions between microtubules and F
      actin. We examine current models for cytokinesis and cell motility in light of
      these findings.

PMID- 10908580
TI  - Regulated expression of nullo is required for the formation of distinct apical
      and basal adherens junctions in the Drosophila blastoderm.
AB  - During cellularization, the Drosophila embryo undergoes a large-scale cytokinetic
      event that packages thousands of syncytial nuclei into individual cells,
      resulting in the de novo formation of an epithelial monolayer in the cortex of
      the embryo. The formation of adherens junctions is one of the many aspects of
      epithelial polarity that is established during cellularization: at the onset of
      cellularization, the Drosophila beta-catenin homologue Armadillo (Arm)
      accumulates at the leading edge of the cleavage furrow, and later to the
      apicolateral region where the zonula adherens precursors are formed. In this
      paper, we show that the basal accumulation of Arm colocalizes with DE-cadherin
      and Dalpha-catenin, and corresponds to a region of tight membrane association,
      which we refer to as the basal junction. Although the two junctions are similar
      in components and function, they differ in their response to the novel
      cellularization protein Nullo. Nullo is present in the basal junction and is
      required for its formation at the onset of cellularization. In contrast, Nullo is
      degraded before apical junction formation, and prolonged expression of Nullo
      blocks the apical clustering of junctional components, leading to morphological
      defects in the developing embryo. These observations reveal differences in the
      formation of the apical and basal junctions, and offer insight into the role of
      Nullo in basal junction formation.

PMID- 10908581
TI  - Genomics comes to cell biology.

PMID- 10908579
TI  - A functional link between dynamin and the actin cytoskeleton at podosomes.
AB  - Cell transformation by Rous sarcoma virus results in a dramatic change of
      adhesion structures with the substratum. Adhesion plaques are replaced by dot
      like attachment sites called podosomes. Podosomes are also found constitutively
      in motile nontransformed cells such as leukocytes, macrophages, and osteoclasts.
      They are represented by columnar arrays of actin which are perpendicular to the
      substratum and contain tubular invaginations of the plasma membrane. Given the
      similarity of these tubules to those generated by dynamin around a variety of
      membrane templates, we investigated whether dynamin is present at podosomes.
      Immunoreactivities for dynamin 2 and for the dynamin 2-binding protein endophilin
      2 (SH3P8) were detected at podosomes of transformed cells and osteoclasts.
      Furthermore, GFP wild-type dynamin 2aa was targeted to podosomes. As shown by
      fluorescence recovery after photobleaching, GFP-dynamin 2aa and GFP-actin had a
      very rapid and similar turnover at podosomes. Expression of the GFP-dynamin
      2aa(G273D) abolished podosomes while GFP-dynamin(K44A) was targeted to podosomes
      but delayed actin turnover. These data demonstrate a functional link between a
      member of the dynamin family and actin at attachment sites between cells and the
      substratum.

PMID- 10908582
TI  - A survey of human disease gene counterparts in the Drosophila genome.

PMID- 10908583
TI  - DNA repair in Drosophila: insights from the Drosophila genome sequence.

PMID- 10908584
TI  - Pre-messenger RNA processing factors in the Drosophila genome.

PMID- 10908585
TI  - Genes encoding Drosophila melanogaster RNA polymerase II general transcription
      factors: diversity in TFIIA and TFIID components contributes to gene-specific
      transcriptional regulation.

PMID- 10908587
TI  - Protein kinases and phosphatases in the Drosophila genome.

PMID- 10908586
TI  - The drosophila melanogaster genome: translation factors and RNA binding proteins.

PMID- 10908588
TI  - Flying through the drosophila cytoskeletal genome.

PMID- 10908589
TI  - Cell death regulation in Drosophila: conservation of mechanism and unique
      insights.

PMID- 10908590
TI  - A genomic analysis of membrane trafficking and neurotransmitter release in
      Drosophila.

PMID- 10908591
TI  - Drosophila melanogaster G protein-coupled receptors.

PMID- 10908592
TI  - The evolution of cell adhesion.

PMID- 10908593
TI  - Amphetamine blocks long-term synaptic depression in the ventral tegmental area.
AB  - The mesolimbic dopamine system is essential for reward-seeking behavior, and
      drugs of abuse are thought to usurp the normal functioning of this pathway. A
      growing body of evidence suggests that glutamatergic synapses on dopamine neurons
      in the ventral tegmental area (VTA) are modified during exposure to addictive
      drugs, producing sensitization, a progressive augmentation in the rewarding
      properties of psychostimulant drugs with repeated exposure. We have tested the
      hypothesis that psychostimulant exposure interferes with the synaptic plasticity
      of glutamatergic inputs to the VTA. We find that excitatory synapses onto VTA
      dopamine neurons exhibit long-term depression (LTD) in response to low-frequency
      stimulation and modest depolarization. LTD in the VTA is NMDA receptor
      independent but is dependent on intracellular Ca(2+) and can be induced by
      driving Ca(2+) into the dopamine neuron. Brief exposure to amphetamine entirely
      blocks LTD at glutamatergic synapses in the VTA, by releasing endogenous dopamine
      that acts at D2 dopamine receptors. The block of LTD is selective, because
      amphetamine has no effect on hippocampal LTD. The LTD we have discovered in the
      VTA is likely to be an important component of excitatory control of the reward
      pathway; amphetamine will inhibit LTD, removing this normal brake on the
      glutamatergic drive to dopamine neurons. This effect of amphetamine represents an
      important mechanism by which normal function of the brain reward system may be
      impaired during substance abuse.

PMID- 10908594
TI  - Modulation of long-term depression by dopamine in the mesolimbic system.
AB  - Long-lasting adaptations in the mesolimbic dopamine (DA) system in response to
      drugs of abuse likely mediate many of the behavioral changes that underlie
      addiction. Recent work suggests that long-term changes in synaptic strength at
      excitatory synapses in the two major components of this system, the nucleus
      accumbens (NAc) and ventral tegmental area, may be particularly important for the
      development of drug-induced sensitization, a process that may contribute to
      addiction, as well as for normal response-reinforcement learning. Using whole
      cell patch-clamp recording techniques from in vitro slice preparations, we have
      examined the existence and basic mechanisms of long-term depression (LTD) at
      excitatory synapses on both GABAergic medium spiny neurons in the NAc and
      dopaminergic neurons in the midbrain. We find that both sets of synapses express
      LTD but that their basic triggering mechanisms differ. Furthermore, DA blocks the
      induction of LTD in the midbrain via activation of D2-like receptors but has
      minimal effects on LTD in the NAc. The existence of LTD in mesolimbic structures
      and its modulation by DA represent mechanisms that may contribute to the
      modifications of neural circuitry that mediate reward-related learning as well as
      the development of addiction.

PMID- 10908596
TI  - Efficacy and stability of quantal GABA release at a hippocampal interneuron
      principal neuron synapse.
AB  - We have examined factors that determine the strength and dynamics of GABAergic
      synapses between interneurons [dentate gyrus basket cells (BCs)] and principal
      neurons [dentate gyrus granule cells (GCs)] using paired recordings in rat
      hippocampal slices at 34 degrees C. Unitary IPSCs recorded from BC-GC pairs in
      high intracellular Cl(-) concentration showed a fast rise and a biexponential
      decay, with mean time constants of 2 and 9 msec. The mean quantal conductance
      change, determined directly at reduced extracellular Ca(2+)/Mg(2+) concentration
      ratios, was 1.7 nS. Quantal release at the BC-GC synapse occurred with short
      delay and was highly synchronized. Analysis of IPSC peak amplitudes and numbers
      of failures by multiple probability compound binomial analysis indicated that
      synaptic transmission at the BC-GC synapse involves three to seven release sites,
      each of which releases transmitter with high probability ( approximately 0.5 in 2
      mm Ca(2+)/1 mm Mg(2+)). Unitary BC-GC IPSCs showed paired-pulse depression (PPD);
      maximal depression, measured for 10 msec intervals, was 37%, and recovery from
      depression occurred with a time constant of 2 sec. Paired-pulse depression was
      mainly presynaptic in origin but appeared to be independent of previous release.
      Synaptic transmission at the BC-GC synapse showed frequency-dependent depression,
      with half-maximal decrease at 5 Hz after a series of 1000 presynaptic action
      potentials. The relative stability of transmission at the BC-GC synapse is
      consistent with a model in which an activity-dependent gating mechanism reduces
      release probability and thereby prevents depletion of the releasable pool of
      synaptic vesicles. Thus several mechanisms converge on the generation of powerful
      and sustained transmission at interneuron-principal neuron synapses in
      hippocampal circuits.

PMID- 10908595
TI  - Complete and long-term rescue of lesioned adult motoneurons by lentiviral
      mediated expression of glial cell line-derived neurotrophic factor in the facial
      nucleus.
AB  - To date, delivery of neurotrophic factors has only allowed to transiently protect
      axotomized facial motoneurons against cell death. In the present report, long
      term protection of these neurons was evaluated by continuously expressing the
      neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) within the
      facial nucleus using a lentiviral vector system. The viral vector was injected
      unilaterally into the facial nucleus of 4-month-old Balb/C mice. In contrast to
      axotomy in other adult rodents, facial nerve lesion in these animals leads to a
      progressive and sustained loss and/or atrophy of >50% of the motoneurons. This
      model thus represents an attractive model to evaluate potential protective
      effects of neurotrophic factors for adult-onset motoneuron diseases, such as
      amyotrophic lateral sclerosis. One month after unilateral lentiviral vector
      injection, the facial nerve was sectioned, and the animals were killed 3 months
      later. Viral delivery of the GDNF gene led to long-term expression and extensive
      diffusion of GDNF within the brainstem. In addition, axotomized motoneurons were
      completely protected against cell death, because 95% of the motoneurons were
      present as demonstrated by both Nissl staining and choline acetyltransferase
      immunoreactivity. Furthermore, GDNF prevented lesion-induced neuronal atrophy and
      maintained proximal motoneuron axons, despite the absence of target cell
      reinnervation. This is the first evidence that viral-mediated delivery of GDNF
      close to the motoneuron cell bodies of the facial nucleus of adult mice can lead
      to complete and long-term protection against lesion-induced cell death.

PMID- 10908597
TI  - Brain localization and behavioral impact of the G-protein-gated K+ channel
      subunit GIRK4.
AB  - Neuronal G-protein-gated potassium (K(G)) channels are activated by several
      neurotransmitters and constitute an important mode of synaptic inhibition in the
      mammalian nervous system. K(G) channels are composed of combinations of four
      subunits termed G protein-gated inwardly rectifying K(+) channels (GIRK). All
      four GIRK subunits are expressed in the brain, and there is a general consensus
      concerning the expression patterns of GIRK1, GIRK2, and GIRK3. The localization
      pattern of GIRK4, however, remains controversial. In this study, we exploit the
      negative background of mice lacking a functional GIRK4 gene to identify neuronal
      populations that contain GIRK4 mRNA. GIRK4 mRNA was detected in only a few
      regions of the mouse brain, including the deep cortical pyramidal neurons, the
      endopiriform nucleus and claustrum of the insular cortex, the globus pallidus,
      the ventromedial hypothalamic nucleus, parafascicular and paraventricular
      thalamic nuclei, and a few brainstem nuclei (e.g., the inferior olive and
      vestibular nuclei). Mice lacking GIRK4 were viable and appeared normal and did
      not display gross deficiencies in locomotor activity, visual tasks, and pain
      perception. Furthermore, GIRK4-deficient mice performed similarly to wild-type
      controls in the passive avoidance paradigm, a test of aversive learning. GIRK4
      knock-out mice did, however, exhibit impaired performance in the Morris water
      maze, a test of spatial learning and memory.

PMID- 10908598
TI  - Developmental regulation of neuronal KCa channels by TGFbeta 1: transcriptional
      and posttranscriptional effects mediated by Erk MAP kinase.
AB  - An avian ortholog of transforming growth factor beta1 (TGFbeta1) is the target
      derived factor responsible for the developmental expression of large-conductance
      Ca(2+)-activated K(+) (K(Ca)) channels in chick ciliary ganglion (CG) neurons
      developing in vivo and in vitro. Application of TGFbeta1 evokes an acute
      stimulation of K(Ca) that can be observed immediately after cessation of a 12 hr
      exposure to this factor, that persists in the presence of protein synthesis
      inhibitors, and that is therefore mediated by posttranslational events. Here we
      show that a single 3 hr exposure to TGFbeta1 can also induce long-lasting
      stimulation of macroscopic K(Ca) that persists for at least 3.5 d after the end
      of the treatment. In contrast to the acute stimulation, this sustained effect is
      dependent on the transcription and synthesis of new proteins at approximately the
      time of TGFbeta1 treatment. However TGFbeta1 does not cause increases in the
      levels of slowpoke alpha subunit transcripts in CG neurons, suggesting that
      induction of some other protein or proteins is required for sustained enhancement
      of macroscopic K(Ca). In addition, application of TGFbeta1 evoked an almost
      immediate but transient phosphorylation of the mitogen-activated protein kinase
      Erk in CG neurons. TGFbeta1-evoked Erk activation was blocked by the specific
      MEK1 inhibitor 2- (2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one (PD98059).
      Moreover, application of PD98059 blocked both acute and sustained K(Ca)
      stimulation evoked by TGFbeta1. These results indicate that TGFbeta1 elicits a
      biphasic stimulation of K(Ca) via activation of an MEK1-Erk pathway and raise the
      possibility that other neuronal effects of TGFbeta superfamily members entail Erk
      activation.

PMID- 10908599
TI  - A voltage-independent calcium current inhibitory pathway activated by muscarinic
      agonists in rat sympathetic neurons requires both Galpha q/11 and Gbeta gamma.
AB  - Calcium current modulation by the muscarinic cholinergic agonist oxotremorine
      methiodide (oxo-M) was examined in sympathetic neurons from the superior cervical
      ganglion of the rat. Oxo-M strongly inhibited calcium currents via voltage
      dependent (VD) and voltage-independent (VI) pathways. These pathways could be
      separated with the use of the specific M(1) acetylcholine receptor antagonist
      M(1)-toxin and with pertussis toxin (PTX) treatment. Expression by nuclear cDNA
      injection of the regulator of G-protein signaling (RGS2) or a phospholipase
      Cbeta1 C-terminal construct (PLCbeta-ct) selectively reduced VI oxo-M modulation
      in PTX-treated and untreated cells. Expression of the Gbetagamma buffers
      transducin (Galpha(tr)) and a G-protein-coupled-receptor kinase (GRK3) construct
      (MAS-GRK3) eliminated oxo-M modulation. Activation of the heterologously
      expressed neurokinin type 1 receptor, a Galpha(q/11)-coupled receptor, resulted
      in VI calcium current modulation. This modulation was eliminated with
      coexpression of Galpha(tr) or MAS-GRK3. Cells expressing Gbeta(1)gamma(2) were
      tonically inhibited via the VD pathway. Application of oxo-M to these cells
      produced VI modulation and reduced the amount of current inhibited via the VD
      pathway. Together, these results confirm the requirement for Gbetagamma in VD
      modulation and implicate Galpha(q)-GTP and Gbetagamma as components in the
      potentially novel VI pathway.

PMID- 10908600
TI  - The Dopamine/D1 receptor mediates the phosphorylation and inactivation of the
      protein tyrosine phosphatase STEP via a PKA-dependent pathway.
AB  - The striatal-enriched protein tyrosine phosphatase (STEP) family is expressed
      within dopaminoceptive neurons of the CNS and is particularly enriched within the
      basal ganglia and related structures. Alternative splicing produces several
      isoforms that are found in a number of subcellular compartments, including
      postsynaptic densities of medium spiny neurons. The variants include STEP(61), a
      membrane-associated protein, and STEP(46), a cytosolic protein. The C terminals
      of these two isoforms are identical, whereas the N-terminal domain of STEP(61)
      contains a novel 172 amino acid sequence that includes several structural motifs
      not present in STEP(46). Amino acid sequencing revealed a number of potential
      phosphorylation sites in both STEP isoforms. Therefore, we investigated the role
      of phosphorylation in regulating STEP activity. Both STEP(61) and STEP(46) are
      phosphorylated on seryl residues by a cAMP-dependent protein kinase (PKA)
      mediated pathway in striatal homogenates. The specific residues phosphorylated in
      STEP(61) were identified by site-directed mutagenesis and tryptic phosphopeptide
      mapping as Ser160 and Ser221, whereas the major site of phosphorylation in
      STEP(46) was shown to be Ser49. Ser160 is located within the unique N terminal of
      STEP(61). Ser221 and Ser49 are equivalent residues present in STEP(61) and
      STEP(46), respectively, and are located at the center of the kinase-interacting
      motif that has been implicated in protein-protein interactions. Phosphorylation
      at this site decreases the activity of STEP in vitro by reducing its affinity for
      its substrate. In vivo studies using striatal slices demonstrated that the
      neurotransmitter dopamine leads to the phosphorylation of STEP via activation of
      D1 receptors and PKA.

PMID- 10908601
TI  - Facilitation of recovery from inactivation by external Na+ and location of the
      activation gate in neuronal Na+ channels.
AB  - Fast inactivation of the Na(+) channel presumably is produced by binding of the
      inactivating peptide (the "hinged lid") to the internal pore mouth of the
      activated channel. It has been shown that recovery from inactivation in Na(+)
      channels begins with a delay, which corresponds to deactivation of the channel,
      and is then followed by an exponential phase, which corresponds to unbinding of
      the inactivating peptide. We found that the exponential phase is approximately
      1.6-fold faster in 150 mm than in 0 mm external Na(+), but the initial delays are
      the same. External Na(+) also increases the late steady-state Na(+) current
      during a step depolarization and shifts the inactivation curve accordingly but
      has no effect on the activation and deactivation kinetics of the current.
      Quantitative analysis of the data reveals that external Na(+) has the same
      facilitation effect on the unbinding of the bound inactivating peptide whether
      the channel is activated or deactivated but has no effect on the other gating
      processes of the channel. These findings suggest that permeating Na(+) ions
      directly knock off the bound inactivating peptide and that channel activation or
      deactivation does not affect the accessibility of the bound inactivation peptide
      to external Na(+). The activation gate (the key gating change transforming a
      Na(+)-nonconducting pore into a Na(+)-conducting one) therefore should not be
      located external to the inactivation gate, which presumably is already located
      close to the internal end of the pore.

PMID- 10908602
TI  - Fos-related antigen 2: potential mediator of the transcriptional activation in
      rat adrenal medulla evoked by repeated immobilization stress.
AB  - The precise mechanisms by which beneficial responses to acute stress are
      transformed into long-term pathological effects of chronic stress are largely
      unknown. Western blot analyses revealed that members of the AP1 transcription
      factor family are differentially regulated by single and repeated stress in the
      rat adrenal medulla, suggesting distinct roles in establishing stress-induced
      patterns of gene expression in this tissue. The induction of c-fos was transient,
      whereas marked elevation of long-lasting Fos-related antigens, including Fra2,
      was observed after repeated immobilization. We investigated DNA protein
      interactions at the AP1-like promoter elements of two stress-responsive genes,
      tyrosine hydroxylase and dopamine beta-hydroxylase. Increased DNA-binding
      activity was displayed in adrenomedullary extract from repeatedly stressed rats,
      which was predominantly composed of c-Jun- and Fra2-containing dimers. The
      induction of Fra2 and increased AP1-like binding activity was reflected in
      sustained transcriptional activation of tyrosine hydroxylase and dopamine beta
      hydroxylase genes after repeated episodes of stress. The functional link between
      Fra2 and regulation of tyrosine hydroxylase and dopamine beta-hydroxylase
      transcription was confirmed in PC12 cells coexpressing this factor and the
      corresponding promoter-reporter gene constructs. These studies emphasize the
      potential importance of stress-evoked increases in the expression of the Fra2
      gene for in vivo adaptations of the adrenal catecholamine producing system.

PMID- 10908603
TI  - Reduced voltage sensitivity of activation of P/Q-type Ca2+ channels is associated
      with the ataxic mouse mutation rolling Nagoya (tg(rol)).
AB  - Recent genetic analyses have revealed an important association of the gene
      encoding the P/Q-type voltage-dependent Ca(2+) channel alpha(1A) subunit with
      hereditary neurological disorders. We have identified the ataxic mouse mutation,
      rolling Nagoya (tg(rol)), in the alpha(1A) gene that leads to a charge
      neutralizing arginine-to-glycine substitution at position 1262 in the voltage
      sensor-forming segment S4 in repeat III. Ca(2+) channel currents in acutely
      dissociated Purkinje cells, where P-type is the dominant type, showed a marked
      decrease in slope and a depolarizing shift by 8 mV of the conductance-voltage
      curve and reduction in current density in tg(rol) mouse cerebella, compared with
      those in wild-type. Compatible functional change was induced by the tg(rol)
      mutation in the recombinant alpha(1A) channel, indicating that a defect in
      voltage sensor of P/Q-type Ca(2+) channels is the direct consequence of the
      tg(rol) mutation. Furthermore, somatic whole-cell recording of mutant Purkinje
      cells displayed only abortive Na(+) burst activity and hardly exhibited Ca(2+)
      spike activity in cerebellar slices. Thus, in tg(rol) mice, reduced voltage
      sensitivity, which may derive from a gating charge defect, and diminished
      activity of the P-type alpha(1A) Ca(2+) channel significantly impair integrative
      properties of Purkinje neurons, presumably resulting in locomotor deficits.

PMID- 10908605
TI  - Cell surface Trk receptors mediate NGF-induced survival while internalized
      receptors regulate NGF-induced differentiation.
AB  - Internalization and transport of a ligand-receptor complex are required to
      initiate cell body responses to target-derived neurotrophin. However, it is not
      known whether internalized receptors and cell surface receptors initiate the same
      signaling pathways and biological responses. Here we use a temperature-sensitive
      mutant of dynamin (G273D) to control the subcellular localization of activated
      NGF receptors (Trks). We show that dynamin function is required for ligand
      dependent endocytosis of Trk receptors. In PC12 cells, nerve growth factor (NGF)
      stimulation promotes both survival and neuronal differentiation. These distinct
      biological responses to NGF are controlled by receptors signaling from different
      locations within the cell. Neuronal differentiation is promoted by catalytically
      active Trks within endosomes in the cell interior. In contrast, survival
      responses are initiated by activated receptors at the cell surface where they
      orchestrate prolonged activation of the kinase Akt. Thus, interactions between
      Trk receptor tyrosine kinases and intracellular signaling molecules are dictated
      both by phosphotyrosine motifs within the receptors and by the intracellular
      location of phosphorylated receptors.

PMID- 10908604
TI  - cAMP-dependent protein kinase inhibits mGluR2 coupling to G-proteins by direct
      receptor phosphorylation.
AB  - One of the primary physiological roles of group II and group III metabotropic
      glutamate receptors (mGluRs) is to presynaptically reduce synaptic transmission
      at glutamatergic synapses. Interestingly, previous studies suggest that
      presynaptic mGluRs are tightly regulated by protein kinases. cAMP analogs and the
      adenylyl cyclase activator forskolin inhibit the function of presynaptic group II
      mGluRs in area CA3 of the hippocampus. We now report that forskolin has a similar
      inhibitory effect on putative mGluR2-mediated responses at the medial perforant
      path synapse and that this effect of forskolin is blocked by a selective
      inhibitor of cAMP-dependent protein kinase (PKA). A series of biochemical and
      molecular studies was used to determine the precise mechanism by which PKA
      inhibits mGluR2 function. Our studies reveal that PKA directly phosphorylates
      mGluR2 at a single serine residue (Ser(843)) on the C-terminal tail region of the
      receptor. Site-directed mutagenesis combined with biochemical measures of mGluR2
      function reveal that phosphorylation of this site inhibits coupling of mGluR2
      from GTP-binding proteins

PMID- 10908606
TI  - Erb and c-Kit receptors have distinctive patterns of expression in adult and
      developing taste papillae and taste buds.
AB  - Twenty four different protein tyrosine kinases (PTKs) were amplified from a taste
      enriched cDNA library using PCR. The expression of four protein tyrosine kinase
      receptors (EGFR, ErbB2, ErbB3, and c-kit) was examined in adult and developing
      rat taste papillae. All four of these receptors were expressed in overlapping
      populations of differentiated taste cells within adult taste buds. Taste bud
      basal cells were ErbB2(+) but did not express the other Erb receptors. During
      prenatal development, the Erb receptors were expressed extensively in the basal
      cells around developing papillae, and ErbB2 and c-kit immunoreactive neuronal
      fibers were seen in close association with taste papillae. In early postnatal
      stages, ErbB2(+) and c-kit(+) neuronal fibers were often seen entering the taste
      papillae epithelium, where new taste buds form, and by postnatal day 2 (P2),
      individual ErbB2(+) and c-kit(+) cells were seen in this region as well. Between
      P3 and P8, c-kit was highly expressed at the bottom of foliate papillae trenches.
      The extensive expression of the Erb and c-kit receptors in adult taste buds and
      in and around developing papillae suggests that these receptors may play a role
      in the prenatal and postnatal development of gustatory papillae and taste buds.

PMID- 10908607
TI  - Viral gene transfer of dominant-negative Kv4 construct suppresses an O2-sensitive
      K+ current in chemoreceptor cells.
AB  - Hypoxia initiates the neurosecretory response of the carotid body (CB) by
      inhibiting one or more potassium channels in the chemoreceptor cells. Oxygen
      sensitive K(+) channels were first described in rabbit CB chemoreceptor cells, in
      which a transient outward K(+) current was reported to be reversibly inhibited by
      hypoxia. Although progress has been made to characterize this current with
      electrophysiological and pharmacological tools, no attempts have been made to
      identify which Kv channel proteins are expressed in rabbit CB chemoreceptor cells
      and to determine their contribution to the native O(2)-sensitive K(+) current. To
      probe the molecular identity of this current, we have used dominant-negative
      constructs to block the expression of functional Kv channels of the Shaker
      (Kv1.xDN) or the Shal (Kv4.xDN) subfamilies, because members of these two
      subfamilies contribute to the transient outward K(+) currents in other
      preparations. Delivery of the constructs into chemoreceptor cells has been
      achieved with adenoviruses that enabled ecdysone-inducible expression of the
      dominant-negative constructs and reporter genes in polycistronic vectors. In
      voltage-clamp experiments, we found that, whereas adenoviral infections of
      chemoreceptor cells with Kv1.xDN did not modify the O(2)-sensitive K(+) current,
      infections with Kv4.xDN suppressed the transient outward current in a time
      dependent manner, significantly depolarized the cells, and abolished the
      depolarization induced by hypoxia. Our work demonstrate that genes of the Shal
      K(+) channels underlie the transient outward, O(2)-sensitive, K(+) current of
      rabbit CB chemoreceptor cells and that this current contributes to the cell
      depolarization in response to low pO(2).

PMID- 10908608
TI  - Clinical mutations in the L1 neural cell adhesion molecule affect cell-surface
      expression.
AB  - Mutations in the L1 neural cell adhesion molecule, a transmembrane glycoprotein,
      cause a spectrum of congenital neurological syndromes, ranging from hydrocephalus
      to mental retardation. Many of these mutations are single amino acid changes that
      are distributed throughout the various domains of the protein. Defective herpes
      simplex virus vectors were used to express L1 protein with the clinical missense
      mutations R184Q and D598N in the Ig2 and Ig6 extracellular domains, respectively,
      and S1194L in the cytoplasmic domain. All three mutant proteins were expressed at
      similar levels in infected cells. Neurite outgrowth of cerebellar granule cells
      was stimulated on astrocytes expressing wild-type or S1194L L1, whereas those
      expressing R184Q and D598N L1 failed to increase neurite length. Live cell
      immunofluorescent staining of L1 demonstrated that most defective vector-infected
      cells did not express R184Q or D598N L1 on their cell surface. This greatly
      diminished cell-surface expression occurred in astrocytes, neurons, and non
      neural cells. In contrast to wild-type or S1194L L1, the R184Q and D598N L1
      proteins had altered apparent molecular weights and remained completely
      endoglycosidase H (endoH)-sensitive, suggesting incomplete post-translational
      processing. We propose that some missense mutations in human L1 impede correct
      protein trafficking, with functional consequences independent of protein
      activity. This provides a rationale for how expressed, full-length proteins with
      single amino acid changes could cause clinical phenotypes similar in severity to
      knock-out mutants.

PMID- 10908609
TI  - Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during
      primary demyelination.
AB  - Metabolic insult results in apoptosis and depletion of mature oligodendrocytes
      during demyelination. To examine the role of insulin-like growth factor-1 (IGF-1)
      during acute demyelination and remyelination in the adult CNS, we exposed
      transgenic mice that continuously express IGF-1 (IGF-1 tg) to cuprizone
      intoxication. Demyelination was observed within the corpus callosum in both wild
      type and IGF-1 tg mice 3 weeks after exposure to cuprizone. Wild-type mice showed
      significant apoptotic mature oligodendrocytes and a dramatic loss of these cells
      within the lesion that resulted in near complete depletion and demyelination by
      week 5. In contrast, the demyelinated corpus callosum of the IGF-1 tg mice was
      near full recovery by week 5. This rapid recovery was apparently caused by
      survival of the mature oligodendrocyte population because apoptosis was
      negligible, and by week 4, the mature oligodendrocyte population was completely
      restored. Furthermore, despite demyelination in both wild-type and IGF-1 tg mice,
      oligodendrocyte progenitors accumulated only in the absence of mature
      oligodendrocytes and failed to accumulate if the mature oligodendrocytes remained
      as demonstrated in the IGF-1 tg mice. These results suggest that IGF-1 may be
      important in preventing the depletion of mature oligodendrocytes in vivo and thus
      facilitates an early recovery from demyelination.

PMID- 10908610
TI  - Ibuprofen suppresses plaque pathology and inflammation in a mouse model for
      Alzheimer's disease.
AB  - The brain in Alzheimer's disease (AD) shows a chronic inflammatory response
      characterized by activated glial cells and increased expression of cytokines and
      complement factors surrounding amyloid deposits. Several epidemiological studies
      have demonstrated a reduced risk for AD in patients using nonsteroidal anti
      inflammatory drugs (NSAIDs), prompting further inquiries about how NSAIDs might
      influence the development of AD pathology and inflammation in the CNS. We tested
      the impact of chronic orally administered ibuprofen, the most commonly used
      NSAID, in a transgenic model of AD displaying widespread microglial activation,
      age-related amyloid deposits, and dystrophic neurites. These mice were created by
      overexpressing a variant of the amyloid precursor protein found in familial AD.
      Transgene-positive (Tg+) and negative (Tg-) mice began receiving chow containing
      375 ppm ibuprofen at 10 months of age, when amyloid plaques first appear, and
      were fed continuously for 6 months. This treatment produced significant
      reductions in final interleukin-1beta and glial fibrillary acidic protein levels,
      as well as a significant diminution in the ultimate number and total area of beta
      amyloid deposits. Reductions in amyloid deposition were supported by ELISA
      measurements showing significantly decreased SDS-insoluble Abeta. Ibuprofen also
      decreased the numbers of ubiquitin-labeled dystrophic neurites and the percentage
      area per plaque of anti-phosphotyrosine-labeled microglia. Thus, the anti
      inflammatory drug ibuprofen, which has been associated with reduced AD risk in
      human epidemiological studies, can significantly delay some forms of AD
      pathology, including amyloid deposition, when administered early in the disease
      course of a transgenic mouse model of AD.

PMID- 10908611
TI  - Delayed mitochondrial dysfunction in excitotoxic neuron death: cytochrome c
      release and a secondary increase in superoxide production.
AB  - An increased production of superoxide has been shown to mediate glutamate-induced
      neuron death. We monitored intracellular superoxide production of hippocampal
      neurons during and after exposure to the glutamate receptor agonist NMDA (300
      microm). During a 30 min NMDA exposure, intracellular superoxide production
      increased significantly and remained elevated for several hours after wash-out of
      NMDA. After a 5 min exposure, superoxide production remained elevated for 10 min,
      but then rapidly returned to baseline. Mitochondrial membrane potential also
      recovered after wash-out of NMDA. However, recovery of mitochondria was transient
      and followed by delayed mitochondrial depolarization, loss of cytochrome c, and a
      secondary rise in superoxide production 4-8 hr after NMDA exposure. Treatment
      with a superoxide dismutase mimetic before the secondary rise conferred the same
      protection against cell death as a treatment before the first. The secondary rise
      could be inhibited by the complex I inhibitor rotenone (in combination with
      oligomycin) and mimicked by the complex III inhibitor antimycin A. To investigate
      the relationship between cytochrome c release and superoxide production, human
      D283 medulloblastoma cells deficient in mitochondrial respiration (rho(-) cells)
      were exposed to the apoptosis-inducing agent staurosporine. Treatment with
      staurosporine induced mitochondrial release of cytochrome c, caspase activation,
      and cell death in control and rho(-) cells. However, a delayed increase in
      superoxide production was only observed in control cells. Our data suggest that
      the delayed superoxide production in excitotoxicity and apoptosis occurs
      secondary to a defect in mitochondrial electron transport and that mitochondrial
      cytochrome c release occurs upstream of this defect.

PMID- 10908612
TI  - The SNARE Vti1a-beta is localized to small synaptic vesicles and participates in
      a novel SNARE complex.
AB  - Specific soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP)
      receptor (SNARE) proteins are required for different membrane transport steps.
      The SNARE Vti1a has been colocalized with Golgi markers and Vti1b with Golgi and
      the trans-Golgi network or endosomal markers in fibroblast cell lines. Here we
      study the distribution of Vti1a and Vti1b in brain. Vti1b was found in synaptic
      vesicles but was not enriched in this organelle. A brain-specific splice variant
      of Vti1a was identified that had an insertion of seven amino acid residues next
      to the putative SNARE-interacting helix. This Vti1a-beta was enriched in small
      synaptic vesicles and clathrin-coated vesicles isolated from nerve terminals.
      Vti1a-beta also copurified with the synaptic vesicle R-SNARE synaptobrevin during
      immunoisolation of synaptic vesicles and endosomes. Therefore, both synaptobrevin
      and Vti1a-beta are integral parts of synaptic vesicles throughout their life
      cycle. Vti1a-beta was part of a SNARE complex in nerve terminals, which bound N
      ethylmaleimide-sensitive factor and alpha-SNAP. This SNARE complex was different
      from the exocytic SNARE complex because Vti1a-beta was not coimmunoprecipitated
      with syntaxin 1 or SNAP-25. These data suggest that Vti1a-beta does not function
      in exocytosis but in a separate SNARE complex in a membrane fusion step during
      recycling or biogenesis of synaptic vesicles.

PMID- 10908614
TI  - Induction of postnatal schwann cell death by the low-affinity neurotrophin
      receptor in vitro and after axotomy.
AB  - Schwann cells express the low-affinity neurotrophin receptor (p75), but no role
      for either the neurotrophins or their cognate receptors in Schwann cell
      development has been established. We have found that Schwann cells isolated from
      postnatal day 1 (P1) or P2 mice that were p75-deficient exhibited potentiated
      survival compared to wild-type cells after growth factor and serum withdrawal.
      There was, however, no disparity in the survival of p75-deficient and wild-type
      Schwann cells isolated at embryonic day 15, suggesting that the death-inducing
      effects of p75 are developmentally regulated. A comparable degree of cell death
      was also observed in the sciatic nerves of both wild-type and p75-deficient mice
      at P1. However, 24 hr after axotomy, there was a 13-fold increase in the
      percentage of apoptotic nuclei in the distal nerve stumps of the transected
      sciatic nerves of neonatal wild-type but not p75-deficient mice. The expression
      of both the p75 and nerve growth factor (NGF) genes was upregulated after axotomy
      in neonatal wild-type nerves. Collectively, these results suggest that NGF
      mediated activation of p75 is likely to be an important mediator of Schwann cell
      apoptosis in the context of peripheral nerve injury.

PMID- 10908613
TI  - Genetic inactivation of an inwardly rectifying potassium channel (Kir4.1 subunit)
      in mice: phenotypic impact in retina.
AB  - The inwardly rectifying potassium channel Kir4.1 has been suggested to underlie
      the principal K(+) conductance of mammalian Muller cells and to participate in
      the generation of field potentials and regulation of extracellular K(+) in the
      retina. To further assess the role of Kir4.1 in the retina, we generated a mouse
      line with targeted disruption of the Kir4.1 gene (Kir4.1 -/-). Muller cells from
      Kir4.1 -/- mice were not labeled with an anti-Kir4.1 antibody, although they
      appeared morphologically normal when stained with an anti-glutamine synthetase
      antibody. In contrast, in Muller cells from wild-type littermate (Kir4.1 +/+)
      mice, Kir4.1 was present and localized to the proximal endfeet and perivascular
      processes. In situ whole-cell patch-clamp recordings showed a 10-fold increase in
      the input resistance and a large depolarization of Kir4.1 -/- Muller cells
      compared with Kir4.1 +/+ cells. The slow PIII response of the light-evoked
      electroretinogram (ERG), which is generated by K(+) fluxes through Muller cells,
      was totally absent in retinas from Kir4.1 -/- mice. The b-wave of the ERG, in
      contrast, was spared in the null mice. Overall, these results indicate that
      Kir4.1 is the principal K(+) channel subunit expressed in mouse Muller glial
      cells. The highly regulated localization and the functional properties of Kir4.1
      in Muller cells suggest the involvement of this channel in the regulation of
      extracellular K(+) in the mouse retina.

PMID- 10908615
TI  - Metabolic stress reversibly activates the Drosophila light-sensitive channels TRP
      and TRPL in vivo.
AB  - Drosophila transient receptor potential (TRP) is a prototypical member of a novel
      family of channel proteins underlying phosphoinositide-mediated Ca(2+) entry.
      Although the initial stages of this signaling cascade are well known, downstream
      events leading to the opening of the TRP channels are still obscure. In the
      present study we applied patch-clamp whole-cell recordings and measurements of
      Ca(2+) concentration by ion-selective microelectrodes in eyes of normal and
      mutant Drosophila to isolate the TRP and TRP-like (TRPL)-dependent currents. We
      report that anoxia rapidly and reversibly depolarizes the photoreceptors and
      induces Ca(2+) influx into these cells in the dark. We further show that openings
      of the light-sensitive channels, which mediate these effects, can be obtained by
      mitochondrial uncouplers or by depletion of ATP in photoreceptor cells, whereas
      the effects of illumination and all forms of metabolic stress were additive.
      Effects similar to those found in wild-type flies were also found in mutants with
      strong defects in rhodopsin, Gq-protein, or phospholipase C, thus indicating that
      the metabolic stress operates at a late stage of the phototransduction cascade.
      Genetic elimination of both TRP and TRPL channels prevented the effects of
      anoxia, mitochondrial uncouplers, and depletion of ATP, thus demonstrating that
      the TRP and TRPL channels are specific targets of metabolic stress. These results
      shed new light on the properties of the TRP and TRPL channels by showing that a
      constitutive ATP-dependent process is required to keep these channels closed in
      the dark, a requirement that would make them sensitive to metabolic stress.

PMID- 10908616
TI  - A role for p27/Kip1 in the control of cerebellar granule cell precursor
      proliferation.
AB  - During development, control of proliferation of neuronal precursor cells plays a
      crucial role in determining the number of neurons. Proliferation is driven by
      mitogens, but how it is terminated remains a mystery. In this study, we examined
      the role of cyclin-dependent kinase inhibitors in the control of proliferation of
      cerebellar granule cell precursors (GCPs). Among the inhibitors we examined, only
      p27/Kip1 (p27) was expressed at significant levels in cells of the granule cell
      lineage in the developing and adult cerebellum. In developing cerebella, p27 was
      expressed in the external germinal layer (the deeper regions), the molecular
      layer, and the granule layer. In adult cerebella, p27 was expressed in the cells
      of the granule layer. We isolated and purified GCPs from cerebella of developing
      mice and examined their bromodeoxyuridine (BrdU) uptake and p27 expression at
      various times. We found that there was an inverse correlation between BrdU uptake
      and p27 expression. Even in the presence of saturating amounts of Sonic hedgehog,
      a potent mitogen, the cells eventually stopped dividing and differentiated,
      expressing p27 strongly. We also examined mice in which one or both copies of the
      p27 gene have been inactivated by targeted gene disruption and found that their
      cerebella were larger than those of wild-type mice. In cell cultures, GCPs
      prepared from p27-deficient mice showed enhanced proliferation compared with GCPs
      from wild-type mice. Taken together, these results suggest that there is an
      intracellular mechanism that stops GCP division and causes GCPs to differentiate
      and that p27 is part of this mechanism.

PMID- 10908618
TI  - BDNF protects the neonatal brain from hypoxic-ischemic injury in vivo via the ERK
      pathway.
AB  - Neurotrophins activate several different intracellular signaling pathways that in
      some way exert neuroprotective effects. In vitro studies of sympathetic and
      cerebellar granule neurons have demonstrated that the survival effects of
      neurotrophins can be mediated via activation of the phosphatidylinositol 3-kinase
      (PI3-kinase) pathway. Neurotrophin-mediated protection of other neuronal types in
      vitro can be mediated via the extracellular signal-related protein kinase (ERK)
      pathway. Whether either of these pathways contributes to the neuroprotective
      effects of neurotrophins in the brain in vivo has not been determined. Brain
      derived neurotrophic factor (BDNF) is markedly neuroprotective against neonatal
      hypoxic-ischemic (H-I) brain injury in vivo. We assessed the role of the ERK and
      PI3-kinase pathways in neonatal H-I brain injury in the presence and absence of
      BDNF. Intracerebroventricular administration of BDNF to postnatal day 7 rats
      resulted in phosphorylation of ERK1/2 and the PI3-kinase substrate AKT within
      minutes. Effects were greater on ERK activation and occurred in neurons.
      Pharmacological inhibition of ERK, but not the PI3-kinase pathway, inhibited the
      ability of BDNF to block H-I-induced caspase-3 activation and tissue loss. These
      findings suggest that neuronal ERK activation in the neonatal brain mediates
      neuroprotection against H-I brain injury, a model of cerebral palsy.

PMID- 10908619
TI  - Depletion of a microtubule-associated motor protein induces the loss of dendritic
      identity.
AB  - Dendrites are short stout tapering processes that are rich in ribosomes and Golgi
      elements, whereas axons are long thin processes of uniform diameter that are
      deficient in these organelles. It has been hypothesized that the unique
      morphological and compositional features of axons and dendrites result from their
      distinct patterns of microtubule polarity orientation. The microtubules within
      axons are uniformly oriented with their plus ends distal to the cell body,
      whereas microtubules within dendrites are nonuniformly oriented. The minus-end
      distal microtubules are thought to arise via their specific transport into
      dendrites by the motor protein known as CHO1/MKLP1. According to this model,
      CHO1/MKLP1 transports microtubules with their minus ends leading into dendrites
      by generating forces against the plus-end-distal microtubules, thus creating drag
      on the plus-end-distal microtubules. Here we show that depletion of CHO1/MKLP1
      from cultured neurons causes a rapid redistribution of microtubules within
      dendrites such that minus-end-distal microtubules are chased back to the cell
      body while plus-end-distal microtubules are redistributed forward. The dendrite
      grows significantly longer and thinner, loses its taper, and acquires a
      progressively more axon-like organelle composition. These results suggest that
      the forces generated by CHO1/MKLP1 are necessary for maintaining the minus-end
      distal microtubules in the dendrite, for antagonizing the anterograde transport
      of the plus-end-distal microtubules, and for sustaining a pattern of microtubule
      organization necessary for the maintenance of dendritic morphology and
      composition. Thus, we would conclude that dendritic identity is dependent on
      forces generated by CHO1/MKLP1.

PMID- 10908617
TI  - Differential modulation of proliferation in the neocortical ventricular and
      subventricular zones.
AB  - Recent studies have implicated the classical neurotransmitters GABA and glutamate
      in the regulation of neural progenitor proliferation. We now show that GABA and
      glutamate have opposite effects on the two neural progenitor populations in the
      ventricular zones (VZs) and subventricular zones (SVZs) of the embryonic
      cerebrum. Application of either molecule to organotypic slice cultures
      dramatically increases proliferation in the VZ by shortening the cell cycle,
      whereas proliferation in the SVZ is decreased. These disparate effects, measured
      both by bromodeoxyuridine uptake and the expansion of retrovirally labeled
      progenitor clones, are mimicked by the application of specific GABA and glutamate
      agonists and are blocked by antagonists. Thus, the relative contributions of the
      VZ and SVZ to neocortical growth may be regulated by differential responsiveness
      to GABA and glutamate.

PMID- 10908620
TI  - Netrin-1 promotes thalamic axon growth and is required for proper development of
      the thalamocortical projection.
AB  - The thalamocortical axon (TCA) projection originates in dorsal thalamus, conveys
      sensory input to the neocortex, and has a critical role in cortical development.
      We show that the secreted axon guidance molecule netrin-1 acts in vitro as an
      attractant and growth promoter for dorsal thalamic axons and is required for the
      proper development of the TCA projection in vivo. As TCAs approach the
      hypothalamus, they turn laterally into the ventral telencephalon and extend
      toward the cortex through a population of netrin-1-expressing cells. DCC and
      neogenin, receptors implicated in mediating the attractant effects of netrin-1,
      are expressed in dorsal thalamus, whereas unc5h2 and unc5h3, netrin-1 receptors
      implicated in repulsion, are not. In vitro, dorsal thalamic axons show biased
      growth toward a source of netrin-1, which can be abolished by netrin-1-blocking
      antibodies. Netrin-1 also enhances overall axon outgrowth from explants of dorsal
      thalamus. The biased growth of dorsal thalamic axons toward the internal capsule
      zone of ventral telencephalic explants is attenuated, but not significantly, by
      netrin-1-blocking antibodies, suggesting that it releases another attractant
      activity for TCAs in addition to netrin-1. Analyses of netrin-1 -/- mice reveal
      that the TCA projection through the ventral telencephalon is disorganized, their
      pathway is abnormally restricted, and fewer dorsal thalamic axons reach cortex.
      These findings demonstrate that netrin-1 promotes the growth of TCAs through the
      ventral telencephalon and cooperates with other guidance cues to control their
      pathfinding from dorsal thalamus to cortex.

PMID- 10908622
TI  - Developmental regulation of a local positive autocontrol of supraoptic neurons.
AB  - Mature oxytocin (OT) and vasopressin (AVP) magnocellular neurons of the
      hypothalamic supraoptic nuclei (SON) autocontrol their electrical activity via
      somatodendritic release of their respective peptides. Because OT and AVP are
      synthesized early in development and could play an important role in the
      maturation of these neurons, we checked whether the peptides are released within
      the SON and act on their secreting neurons during 3 weeks of postnatal
      development. We used patch-clamp recordings from SON neurons in rat hypothalamic
      horizontal slices to show that the spontaneous electrical activity of immature
      SON neurons is blocked by OT or AVP receptor antagonists, demonstrating a basal
      somatodendritic release of the peptides. Application of OT or AVP depolarizes SON
      neurons and stimulates activity typical of the corresponding mature neurons. This
      effect is directly on SON neurons because it is recorded in dissociated neurons.
      Radioimmunoassays from isolated SON were used to show that each peptide
      facilitates its own release at a somatodendritic level, exhibiting a self
      sustaining positive feedback loop. This autocontrol is not uniform during
      development because the proportion of neurons depolarized by the peptides, the
      amplitude of the depolarization, and the propensity of the peptides to facilitate
      their own release are maximal during the second postnatal week and decrease
      thereafter. These data are consistent with a role of autocontrol in the
      maturation of SON neurons because it is maximal during the delimited period of
      postnatal development that corresponds to the period of major synapse formation.

PMID- 10908621
TI  - Neocortical origin and tangential migration of guidepost neurons in the lateral
      olfactory tract.
AB  - The early-generated neurons designated as lot cells specifically mark the future
      site of the lateral olfactory tract (LOT) and guide LOT axons. We investigated
      the mechanism of how lot cells develop and get localized in the LOT position. Lot
      cells differentiated from neuroepithelial cells in all regions of the neocortex
      but not from those in the ganglionic eminence in culture. Cell tracing analyses
      demonstrated that lot cells generated from the neocortex subsequently followed a
      tangential migration stream ventrally toward the LOT position. Mutant mouse
      embryos lacking the function of transcription factor Gli3 showed disturbances of
      the migration stream and translocation of lot cells in the dorsal telencephalon.
      These results reveal a new type of neuronal migration in the telencephalon and
      introduce an unexpected dramatic feature of the earliest regionalization of the
      telencephalon.

PMID- 10908623
TI  - Long-lasting inhibitory synaptic depression is age- and calcium-dependent.
AB  - The developmental refinement of excitatory synapses is often influenced by
      neuronal activity, and underlying synaptic mechanisms have been suggested. In
      contrast, few studies have asked whether inhibitory synapses are reorganized
      during development and whether this is accompanied by use-dependent changes of
      inhibitory synaptic strength. The topographic inhibitory projection from the
      medial nucleus of the trapezoid body (MNTB) to the lateral superior olive (LSO)
      undergoes synapse elimination during development (Sanes and Takacs, 1993). To
      determine whether there is an associated period of synaptic plasticity, whole
      cell recordings were obtained from developing LSO neurons of gerbils in a brain
      slice preparation. In current-clamp recordings, low-frequency stimulation of the
      MNTB led to a decline in IPSP amplitude by 43%. In voltage-clamp recordings,
      hyperpolarized LSO neurons also exhibited a long-lasting depression of MNTB
      evoked inhibitory synaptic currents (34%) after low-frequency stimulation. When
      LSO neurons were depolarized, low-frequency stimulation of the MNTB produced a
      significantly larger inhibitory synaptic depression (59%). This synaptic
      plasticity declined dramatically by postnatal days 17-19. Similar to well studied
      forms of excitatory synaptic plasticity, inhibitory depression depended on
      postsynaptic calcium. We propose that such activity-dependent synaptic depression
      may support the developmental rearrangement of inhibitory terminals as they
      compete with neighboring excitatory and/or inhibitory inputs.

PMID- 10908624
TI  - Prominence of direct entorhinal-CA1 pathway activation in sensorimotor and
      cognitive tasks revealed by 2-DG functional mapping in nonhuman primate.
AB  - The trisynaptic pathway from entorhinal cortex to the hippocampus has long been
      regarded as the major route of information transfer underlying memory
      consolidation. Most physiological studies of this pathway involve recording from
      hippocampal slices. We have used both single- and double-label 2-deoxyglucose
      autoradiographic methods to image the pattern of activation in the hippocampal
      formation of 14 rhesus monkeys performing cognitive tasks, varying in content
      (spatial or nonspatial), process (working memory or associative memory), and mode
      of response (oculomotor or manual). These studies revealed a highly
      differentiated pattern of metabolic activation throughout the rostrocaudal extent
      of the hippocampal formation that was common to all behavioral conditions
      examined. This pattern consisted of intense activation of the stratum lacunosum
      moleculare of CA1 and the subiculum, contrasting with barely detectable activity
      in CA3 and modest activation in the dentate gyrus, which did not include its
      molecular layer. These findings indicate a remarkable invariance in hippocampal
      activation under conditions of varied content, varied process, and varied mode of
      response and an heretofore-unappreciated preferential engagement of the direct
      rather than the trisynaptic pathway during performance of a wide range of
      behavioral tasks.

PMID- 10908625
TI  - Eye position signal modulates a human parietal pointing region during memory
      guided movements.
AB  - Using functional magnetic resonance imaging, we examined the signal in parietal
      regions that were selectively activated during delayed pointing to flashed visual
      targets and determined whether this signal was dependent on the fixation position
      of the eyes. Delayed pointing activated a bilateral parietal area in the
      intraparietal sulcus (rIPS), rostral/anterior to areas activated by saccades.
      During right-hand pointing to centrally located targets, the left rIPS region
      showed a significant increase in activation when the eye position was rightward
      compared with leftward. As expected, activation in motor cortex showed no
      modulation when only eye position changed. During pointing to retinotopically
      identical targets, the left rIPS region again showed a significant increased
      signal when the eye position was rightward compared with leftward. Conversely,
      when pointing with the left arm, the right rIPS showed an increase in signal when
      eye position was leftward compared with rightward. The results suggest that the
      human parietal hand/arm movement region (rIPS), like monkey parietal areas
      (Andersen et al., 1985), exhibits an eye position modulation of its activity;
      modulation that may be used to transform the coordinates of the retinotopically
      coded target position into a motor error command appropriate for the wrist.

PMID- 10908626
TI  - Malformation of the functional organization of somatosensory cortex in adult
      ephrin-A5 knock-out mice revealed by in vivo functional imaging.
AB  - The molecular mechanisms that coordinate the functional organization of the
      mammalian neocortex are largely unknown. We tested the involvement of a putative
      guidance label, ephrin-A5, in the functional organization of the somatosensory
      cortex by quantifying the functional representations of individual whiskers in
      vivo in adult ephrin-A5 knock-out mice, using intrinsic signal optical imaging.
      In wild-type mice ephrin-A5 is expressed in a gradient in the somatosensory
      cortex during development. In adult ephrin-A5 knock-out mice, we found a spatial
      gradient of change in the amount of cortical territory shared by individual
      whisker functional representations across the somatosensory cortex, as well as a
      gradient of change in the distance between the functional representations. Both
      gradients of change were in correspondence with the developmental expression
      gradient of ephrin-A5 in wild-type mice. These changes involved malformations of
      the cortical spacing of the thalamocortical components, without concurrent
      malformations of the intracortical components of individual whisker functional
      representations. Overall, these results suggest that a developmental guidance
      label, such as ephrin-A5, is involved in establishing certain spatial
      relationships of the functional organization of the adult neocortex, and they
      underscore the advantage of investigating gene manipulation using in vivo
      functional imaging.

PMID- 10908627
TI  - Rescue of locomotor impairment in dopamine D2 receptor-deficient mice by an
      adenosine A2A receptor antagonist.
AB  - In Parkinson's disease a degeneration of dopaminergic neurons of the
      nigrostriatal pathway is observed. Loss of dopaminergic regulation of striatal
      neuron activity results in altered motor functions. Adenosine A2A (A2AR) and
      dopamine D2 (D2R) receptors are colocalized in striatal medium spiny neurons. It
      has been proposed that adenosine binding to A2AR lowers the affinity of dopamine
      for D2R, thus modulating the function of this receptor. Absence of D2R in
      knockout mice (D2R-/-) results in impaired locomotion and coordinated movements.
      This indicates that absence of dopamine in Parkinson's disease might principally
      affect D2R-mediated effects with regard to locomotor functions. A2AR-selective
      antagonists have been demonstrated to have anti- parkinsonian activities in
      various models of Parkinson's disease in rodents and nonhuman primates. In this
      article, D2R-/- mice were used to explore the possibility that an A2AR antagonist
      might reestablish their motor impairment. Interestingly, blockade of A2AR rescues
      the behavioral parameters altered in D2R-/- mice. In addition, the level of
      expression of enkephalin and substance P, which were altered in D2R-/-, were also
      reestablished to normal levels after A2AR antagonist treatment. These results
      show that A2AR and D2R have antagonistic and independent activities in
      controlling neuronal and motor functions in the basal ganglia. They also provide
      evidence that selective A2AR antagonists can exhibit their anti-parkinsonian
      activities through a nondopaminergic mechanism.

PMID- 10908628
TI  - Remote episodic memory deficits in patients with unilateral temporal lobe
      epilepsy and excisions.
AB  - The nature of remote memory impairment in patients with medial temporal lobe
      damage is the subject of some debate. While some investigators have found that
      retrograde amnesia in such patients is temporally graded, with relative sparing
      of remote memories (Squire and Alvarez, 1995), others contend that impairment is
      of very long duration and that remote memories are not necessarily spared
      (Sanders and Warrington, 1971; Nadel and Moscovitch, 1997). In this study, remote
      memory was assessed in 25 patients with unilateral temporal lobe epilepsy and 22
      non-neurologically impaired controls using the Autobiographical Memory Interview
      (Kopelman et al., 1989). Results indicate that patients have impaired personal
      episodic memory but intact personal semantic memory. The impairment extends even
      to the most remote time periods in early childhood, long before seizure onset in
      many patients. As well, patients awaiting temporal lobectomy for control of
      seizures perform as poorly as those who have already undergone resective surgery.
      These results support the hypothesis that temporal lobe damage or dysfunction,
      caused by recurrent seizures or surgical excision, results in extensive
      retrograde amnesia for personal episodic memories. Interestingly, patients with
      radiological evidence of hippocampal sclerosis were not significantly more
      impaired than those without obvious sclerosis. These results indicate that even
      minimal damage to medial temporal lobes results in significant impairment to
      autobiographical episodic memory. These findings are more compatible with a
      memory loss or retrieval deficit rather than a consolidation account of remote
      memory impairment.

PMID- 10908629
TI  - Role of inspiratory pacemaker neurons in mediating the hypoxic response of the
      respiratory network in vitro.
AB  - In severe hypoxia the breathing frequency is modulated in a biphasic manner: an
      initial increase (augmentation) is followed by a depression and cessation of
      breathing (apnea). Using a mouse slice preparation that contains the functional
      respiratory network, we aimed at identifying the neurons responsible for this
      frequency modulation. Whole-cell patch recordings revealed that expiratory
      neurons become tonically active during anoxia, indicating that these neurons
      cannot be responsible for the respiratory frequency modulation. Inspiratory
      neurons tended to depolarize (by 6.9 mV; n = 9), and the frequency of rhythmic
      activity was significantly increased during anoxia (from 0.16 to 0.4 Hz; n = 9).
      After the blockade of network activity with 6-cyano-7-nitroquinoxaline-2, 3
      dione, most inspiratory neurons became tonically active (72%; n = 25, non
      pacemaker). In anoxia, the membrane potential of these non-pacemaker neurons did
      not change (-0.26 mV; n = 6), and their tonic activity ceased. Only a
      subpopulation of inspiratory neurons remained rhythmically active in the absence
      of network activity (pacemaker neurons, 28%, 7 of 25 inspiratory neurons). In
      anoxia two subgroups of pacemaker neurons were differentiated; one group showed a
      transient increase in the bursting activity, followed by a decrease and cessation
      of rhythmic activity. These neurons tended to depolarize (by 10.3 mV) during
      anoxia. The second group remained rhythmic during the entire anoxic exposure and
      exhibited no depolarization. The time course of the frequency modulation in all
      pacemaker neurons resembled that of the intact network. We conclude that
      pacemaker neurons are primarily responsible for the frequency modulation in
      anoxia and that in the respiratory network there is a strict separation between
      rhythm- and pattern-generating mechanisms.

PMID- 10908630
TI  - Nonphotic entrainment by 5-HT1A/7 receptor agonists accompanied by reduced Per1
      and Per2 mRNA levels in the suprachiasmatic nuclei.
AB  - In mammals, the environmental light/dark cycle strongly synchronizes the
      circadian clock within the suprachiasmatic nuclei (SCN) to 24 hr. It is well
      known that not only photic but also nonphotic stimuli can entrain the SCN clock.
      Actually, many studies have shown that a daytime injection of 8-hydroxy-2-(di-n
      propylamino) tetralin (8-OH DPAT), a serotonin 1A/7 receptor agonist, as a
      nonphotic stimulus induces phase advances in hamster behavioral circadian rhythms
      in vivo, as well as the neuron activity rhythm of the SCN in vitro. Recent
      reports suggest that mammalian homologs of the Drosophila clock gene, Period
      (Per), are involved in photic entrainment. Therefore, we examined whether phase
      advances elicited by 8-OH DPAT were associated with a change of Period mRNA
      levels in the SCN. In this experiment, we cloned partial cDNAs encoding hamster
      Per1, Per2, and Per3 and observed both circadian oscillation and the light
      responsiveness of Period. Furthermore, we found that the inhibitory effect of 8
      OH DPAT on hamster Per1 and Per2 mRNA levels in the SCN occurred only during the
      hamster's mid-subjective day, but not during the early subjective day or
      subjective night. The present findings demonstrate that the acute and circadian
      time-dependent reduction of Per1 and/or Per2 mRNA in the hamster SCN by 8-OH DPAT
      is strongly correlated with the phase resetting in response to 8-OH DPAT.

PMID- 10908632
TI  - Selection of currently relevant memories by the human posterior medial
      orbitofrontal cortex.
AB  - We have demonstrated previously that patients producing spontaneous
      confabulations fail to suppress currently irrelevant memory traces, so that they
      act and think on the basis of a false, temporally displaced (past) reality. All
      spontaneous confabulators had anterior limbic damage, in particular of the
      orbitofrontal cortex and basal forebrain. These findings indicated that these
      structures are essential for distinguishing between mental representations of
      ongoing reality and currently irrelevant memories. In the present study, we used
      a similar experimental paradigm as in our clinical studies and H(2)(15)O positron
      emission tomography to explore the selection of currently relevant memories by
      the healthy human brain. Subjects were repeatedly presented with the same set of
      pictures, arranged in different order each time, and were requested to indicate
      picture recurrences within the runs. Thus, performance in the first run depended
      on new learning, whereas subsequent runs required the distinction between picture
      repetitions within the current run ("now") and previous picture presentations in
      earlier runs. Whereas initial learning activated medial temporal structures,
      subsequent runs provoked circumscribed posterior medial orbitofrontal activation.
      We suggest that this area is essential for sorting out mental associations that
      pertain to ongoing reality.

PMID- 10908633
TI  - Occlusion and the interpretation of visual motion: perceptual and neuronal
      effects of context.
AB  - Visual motion can be represented in terms of the dynamic visual features in the
      retinal image or in terms of the moving surfaces in the environment that give
      rise to these features. For natural images, the two types of representation are
      necessarily quite different because many moving features are only spuriously
      related to the motion of surfaces in the visual scene. Such "extrinsic" features
      arise at occlusion boundaries and may be detected by virtue of the depth-ordering
      cues that exist at those boundaries. Although a number of studies have provided
      evidence of the impact of depth ordering on the perception of visual motion, few
      attempts have been made to identify the neuronal substrate of this interaction.
      To address this issue, we devised a simple contextual manipulation that decouples
      surface motion from the motions of visual image features. By altering the depth
      ordering between a moving pattern and abutting static regions, the perceived
      direction of motion changes dramatically while image motion remains constant.
      When stimulated with these displays, many neurons in the primate middle temporal
      visual area (area MT) represent the implied surface motion rather than the motion
      of retinal image features. These neurons thus use contextual depth-ordering
      information to achieve a representation of the visual scene consistent with
      perceptual experience.

PMID- 10908631
TI  - kappa -opioid receptor agonists modulate visceral nociception at a novel,
      peripheral site of action.
AB  - kappa-opioid receptor agonists (kappa-ORAs) have been shown to modulate visceral
      nociception through an interaction with a peripheral, possibly novel, kappa
      opioid-like receptor. We used in the present experiments an antisense strategy to
      further explore the hypothesis that kappa-ORA effects in the colon are produced
      at a site different from the cloned kappa-opioid receptor (KOR). An antisense
      oligodeoxynucleotide (ODN) to the cloned rat KOR was administered intrathecally
      (12.5 microg, twice daily for 4 d) to specifically knock-down the cloned KOR.
      Efficacy of the KOR antisense ODN treatment was behaviorally evaluated by
      assessing the antinociceptive effects of peripherally administered kappa- (EMD
      61, 753 and U 69,593), mu- (DAMGO) and delta- (deltorphin) ORAs in the formalin
      test. Intrathecal antisense, but not mismatch ODN blocked the actions of EMD
      61,753 and U 69,593 without affecting the actions of DAMGO or deltorphin; a
      complete recovery of antinociceptive actions of the kappa-ORA EMD 61,753 was
      observed 10 d after the termination of antisense ODN treatment. In contrast, the
      ability of EMD 61,753 to dose-dependently attenuate responses of pelvic nerve
      afferent fibers to noxious colonic distension was unaffected in the same rats in
      which the antisense ODN effectively knocked-down the KOR as assessed in the
      formalin test. Additionally, Western blot analysis demonstrated a significant
      downregulation of KOR protein in the L4-S1 dorsal root ganglia of antisense, but
      not mismatch ODN-treated rats. The present results support the existence of a non
      kappa-opioid receptor site of action localized in the colon.

PMID- 10908634
TI  - Discovery of paralogous nuclear gene sequences coding for the second-largest
      subunit of RNA polymerase II (RPB2) and their phylogenetic utility in gentianales
      of the asterids.
AB  - Paralogous sequences of the RPB2 gene are demonstrated in the angiosperm order
      Gentianales. Two different copies were found by using different PCR primer pairs
      targeting a region that corresponds to exons 22-24 in the Arabidopsis RPB2 gene.
      One of the copies (RPB2-d) lacks introns in this region, whereas the other has
      introns at locations corresponding to those of green plants previously
      investigated. When analyzed with other available RPB2 sequences from this region,
      all 28 RPB2-d sequences obtained from the Gentianales and the four sequences from
      the Lamiales form a monophyletic group, together with a previously published
      tomato cDNA sequence. The substitution patterns, relative rates of change, and
      nucleotide compositions of the two paralogous RPB2 exon regions are similar, and
      none of them shows any signs of being a pseudogene. Although multiple copies of
      similar, paralogous sequences can confound phylogenetic interpretations, the lack
      of introns in RPB2-d make a priori homology assessment easy. The phylogenetic
      utility of RPB2-d within the Gentianales is evaluated in comparison with the
      chloroplast genes ndhF and rbcL. The hierarchical information in the RPB2-d
      region sequenced is more incongruent with that of the plastid genes than the
      plastid genes are with each other as determined by incongruence length difference
      tests. In contrast to the plastid genes, parsimony-informative third codon
      positions of RPB2 have a significantly higher rate of change than first and
      second positions. Topologically, the trees from the three genes are similar, and
      the differences are usually only weakly supported. In terms of support, RPB2
      gives the highest jackknife support per sequenced nucleotide, whereas ndhF gives
      the highest Bremer support per sequenced nucleotide. The RPB2-d locus has the
      potential to be a valuable nuclear marker for determination of phylogenetic
      relationships within the euasterid I group of plants.

PMID- 10908635
TI  - Core histones of the amitochondriate protist, Giardia lamblia.
AB  - Genes coding for the core histones H2a, H2b, H3, and H4 of Giardia lamblia were
      sequenced. A conserved organism- and gene-specific element, GRGCGCAGATTTVGG, was
      found upstream of the coding region in all core histone genes. The derived amino
      acid sequences of all four histones were similar to their homologs in other
      eukaryotes, although they were among the most divergent members of this protein
      family. Comparative protein structure modeling combined with energy evaluation of
      the resulting models indicated that the G. lamblia core histones individually and
      together can assume the same three-dimensional structures that were established
      by X-ray crystallography for Xenopus laevis histones and the nucleosome core
      particle. Since G. lamblia represents one of the earliest-diverging eukaryotes in
      many different molecular trees, the structure of its histones is potentially of
      relevance to understanding histone evolution. The G. lamblia proteins do not
      represent an intermediate stage between archaeal and eukaryotic histones.

PMID- 10908636
TI  - A test for concordance between the multilocus genealogies of genes and
      microsatellites in the pathogenic fungus Coccidioides immitis.
AB  - Uncovering the correct phylogeny of closely related species requires analysis of
      multiple gene genealogies or, alternatively, genealogies inferred from the
      multiple alleles found at highly polymorphic loci, such as microsatellites.
      However, a concern in using microsatellites is that constraints on allele sizes
      may occur, resulting in homoplasious distributions of alleles, leading to
      incorrect phylogenies. Seven microsatellites from the pathogenic fungus
      Coccidioides immitis were sequenced for 20 clinical isolates chosen to represent
      the known genetic diversity of the pathogen. An organismal phylogeny for C.
      immitis was inferred from microsatellite-flanking sequence polymorphisms and
      other restriction fragment length polymorphism-containing loci. Two
      microsatellite genetic distances were then used to determine phylogenies for C.
      immitis, and the trees found by these three methods were compared. Congruence
      between the organismal and microsatellite phylogenies occurred when
      microsatellite distances were based on simple allele frequency data. However,
      complex mutation events at some loci made distances based on stepwise mutation
      models unreliable. Estimates of times of divergence for the two species of C.
      immitis based on microsatellites were significantly lower than those calculated
      from flanking sequence, most likely due to constraints on microsatellite allele
      sizes. Flanking-sequence insertions/deletions significantly decreased the
      accuracy of genealogical information inferred from microsatellite loci and caused
      interspecific length homoplasies at one of the seven loci. Our analysis shows
      that microsatellites are useful phylogenetic markers, although care should be
      taken to choose loci with appropriate flanking sequences when they are intended
      for use in evolutionary studies.

PMID- 10908637
TI  - Evolution of the large secreted gel-forming mucins.
AB  - Mucins, the major component of mucus, contain tandemly repeated sequences that
      differ from one mucin to another. Considerable advances have been made in recent
      years in our knowledge of mucin genes. The availability of the complete genomic
      and cDNA sequences of MUC5B, one of the four human mucin genes clustered on
      chromosome 11, provides an exemplary model for studying the molecular evolution
      of large mucins. The emerging picture is one of expansion of mucin genes by gene
      duplications, followed by internal repeat expansion that strictly preserves
      frameshift. Computational and phylogenetic analyses have permitted the proposal
      of an evolutionary history of the four human mucin genes located on chromosome 11
      from an ancestor gene common to the human von Willebrand factor gene and the
      suggestion of a model for the evolution of the repeat coding portion of the MUC5B
      gene from a hypothetical ancestral minigene. The characterization of MUC5B, a
      member of the large secreted gel-forming mucin family, offers a new model for the
      comparative study of the structure-function relationship within this important
      family.

PMID- 10908638
TI  - Evolution of gypsy endogenous retrovirus in the Drosophila obscura species group.
AB  - The Ty3/gypsy family of retroelements is closely related to retroviruses, and
      some of their members have an open reading frame resembling the retroviral gene
      env. Sequences homologous to the gypsy element from Drosophila melanogaster are
      widely distributed among Drosophila species. In this work, we report a
      phylogenetic study based mainly on the analysis of the 5' region of the env gene
      from several species of the obscura group, and also from sequences already
      reported of D. melanogaster, Drosophila virilis, and Drosophila hydei. Our
      results indicate that the gypsy elements from species of the obscura group
      constitute a monophyletic group which has strongly diverged from the prototypic
      D. melanogaster gypsy element. Phylogenetic relationships between gypsy sequences
      from the obscura group are consistent with those of their hosts, indicating
      vertical transmission. However, D. hydei and D. virilis gypsy sequences are
      closely related to those of the affinis subgroup, which could be indicative of
      horizontal transmission.

PMID- 10908639
TI  - An analysis of G-U base pair occurrence in eukaryotic 5S rRNAs.
AB  - The structure-function relationship in RNA molecules is a key to understanding of
      the expression of genetic information. Various types of RNA play crucial roles at
      almost every step of protein biosynthesis. In recent years, it has been shown
      that one of the most important structural elements in RNA is a wobble pair G-U.
      In this paper, we present for the first time an analysis of the distribution of G
      U pairs in eukaryotic 5S ribosomal RNAs. Interestingly, the G-U pair in 5S rRNA
      species is predominantly found in two intrahelical regions of the stems I and V
      and at the junction of helix IV and loop A. The distribution of G-U pairs and the
      nature of adjacent bases suggests their possible role as a recognition site in
      interactions with other components of protein biosynthesis machinery.

PMID- 10908640
TI  - The evolution of the thyroid hormone distributor protein transthyretin in the
      order insectivora, class mammalia.
AB  - Thyroid hormones are involved in the regulation of growth and metabolism in all
      vertebrates. Transthyretin is one of the extracellular proteins with high
      affinity for thyroid hormones which determine the partitioning of these hormones
      between extracellular compartments and intracellular lipids. During vertebrate
      evolution, both the tissue pattern of expression and the structure of the gene
      for transthyretin underwent characteristic changes. The purpose of this study was
      to characterize the position of Insectivora in the evolution of transthyretin in
      eutherians, a subclass of Mammalia. Transthyretin was identified by thyroxine
      binding and Western analysis in the blood of adult shrews, hedgehogs, and moles.
      Transthyretin is synthesized in the liver and secreted into the bloodstream,
      similar to the situation for other adult eutherians, birds, and diprotodont
      marsupials, but different from that for adult fish, amphibians, reptiles,
      monotremes, and Australian polyprotodont marsupials. For the characterization of
      the structure of the gene and the processing of mRNA for transthyretin, cDNA
      libraries were prepared from RNA from hedgehog and shrew livers, and full-length
      cDNA clones were isolated and sequenced. Sections of genomic DNA in the regions
      coding for the splice sites between exons 1 and 2 were synthesized by polymerase
      chain reaction and sequenced. The location of splicing was deduced from
      comparison of genomic with cDNA nucleotide sequences. Changes in the nucleotide
      sequence of the transthyretin gene during evolution are most pronounced in the
      region coding for the N-terminal region of the protein. Both the derived overall
      amino sequences and the N-terminal regions of the transthyretins in Insectivora
      were found to be very similar to those in other eutherians but differed from
      those found in marsupials, birds, reptiles, amphibians, and fish. Also, the
      pattern of transthyretin precursor mRNA splicing in Insectivora was more similar
      to that in other eutherians than to that in marsupials, reptiles, and birds.
      Thus, in contrast to the marsupials, with a different pattern of transthyretin
      gene expression in the evolutionarily "older" polyprotodonts compared with the
      evolutionarily "younger" diprotodonts, no separate lineages of transthyretin
      evolution could be identified in eutherians. We conclude that transthyretin gene
      expression in the liver of adult eutherians probably appeared before the
      branching of the lineages leading to modern eutherian species.

PMID- 10908641
TI  - Distribution and abundance of microsatellites in the yeast genome can Be
      explained by a balance between slippage events and point mutations.
AB  - We fit a Markov chain model of microsatellite evolution introduced by Kruglyak et
      al. to data on all di-, tri-, and tetranucleotide repeats in the yeast genome.
      Our results suggest that many features of the distribution of abundance and
      length of microsatellites can be explained by this simple model, which
      incorporates a competition between slippage events and base pair substitutions,
      with no need to invoke selection or constraints on the lengths. Our results
      provide some new information on slippage rates for individual repeat motifs,
      which suggest that AT-rich trinucleotide repeats have higher slippage rates. As
      our model predicts, we found that many repeats were adjacent to shorter repeats
      of the same motif. However, we also found a significant tendency of
      microsatellites of different motifs to cluster.

PMID- 10908642
TI  - Bias in phylogenetic reconstruction of vertebrate rhodopsin sequences.
AB  - Two spurious nodes were found in phylogenetic analyses of vertebrate rhodopsin
      sequences in comparison with well-established vertebrate relationships. These
      spurious reconstructions were well supported in bootstrap analyses and occurred
      independently of the method of phylogenetic analysis used (parsimony, distance,
      or likelihood). Use of this data set of vertebrate rhodopsin sequences allowed us
      to exploit established vertebrate relationships, as well as the considerable
      amount known about the molecular evolution of this gene, in order to identify
      important factors contributing to the spurious reconstructions. Simulation
      studies using parametric bootstrapping indicate that it is unlikely that the
      spurious nodes in the parsimony analyses are due to long branches or other
      topological effects. Rather, they appear to be due to base compositional bias at
      third positions, codon bias, and convergent evolution at nucleotide positions
      encoding the hydrophobic residues isoleucine, leucine, and valine. LogDet
      distance methods, as well as maximum-likelihood methods which allow for
      nonstationary changes in base composition, reduce but do not entirely eliminate
      support for the spurious resolutions. Inclusion of five additional rhodopsin
      sequences in the phylogenetic analyses largely corrected one of the spurious
      reconstructions while leaving the other unaffected. The additional sequences not
      only were more proximal to the corrected node, but were also found to have
      intermediate levels of base composition and codon bias as compared with
      neighboring sequences on the tree. This study shows that the spurious
      reconstructions can be corrected either by excluding third positions, as well as
      those encoding the amino acids Ile, Val, and Leu (which may not be ideal, as
      these sites can contain useful phylogenetic signal for other parts of the tree),
      or by the addition of sequences that reduce problems associated with convergent
      evolution.

PMID- 10908643
TI  - Relationship between the occurrence of cysteine in proteins and the complexity of
      organisms.
AB  - The occurrence and relative positions of cysteine residues were investigated in
      proteins of various species. Considering random mathematical occurrence for an
      amino acid coded by two codons (3. 28%), cysteine is underrepresented in all
      organisms investigated. Representation of cysteine appears to correlate
      positively with the complexity of the organism, ranging between 2.26% in mammals
      and 0. 5% in some members of the Archeabacteria order. This observation, together
      with the results obtained from comparison of cysteine content of various
      ribosomal proteins, indicates that evolution takes advantage of increased use of
      cysteine residues. In all organisms studied except plants, two cysteines are
      frequently found two amino acid residues apart (C-(X)(2)-C motif). Such a motif
      is known to be present in a variety of metal-binding proteins and
      oxidoreductases. Remarkably, more than 21% of all of cysteines were found within
      the C-(X)(2)-C motifs in ARCHEA.: This observation may indicate that cysteine
      appeared in ancient metal-binding proteins first and was introduced into other
      proteins later.

PMID- 10908644
TI  - Origin and evolution of the regulatory gene male-specific lethal-3.
AB  - Dosage compensation in Drosophila is mediated by genes known as "male-specific
      lethals" (msls). Several msls, including male-specific lethal-3 (msl-3), encode
      proteins of unknown function. We cloned the Drosophila virilis msl-3 gene. Using
      the information provided by the sequences of the Drosophila melanogaster and D.
      virilis genes, we found that sequences of other species can be aligned along
      their entire lengths with msl-3. Among them, there are genes in yeasts (the
      Schizosaccharomyces pombe Alp13 gene, as well as a putative Alp13 homolog, found
      in Saccharomyces cerevisae) and in mammals (MRG15 and MSL3L1 and their relatives)
      plus uncharacterized sequences of the nematode Caenorhabditis elegans and the
      plants Arabidopsis thaliana, Lycopersicon esculentum, and Zea mays. A second
      Drosophila gene of this family has also been found. It is thus likely that msl-3
      like genes are present in all eukaryotes. Phylogenetic analyses suggest that msl
      3 is orthologous to the mammalian MSL3L1 genes, while the second Drosophila
      melanogaster gene (which we have called Dm MRG15) is orthologous to mammalian
      MRG15. These analyses also suggest that the msl-3/MRG15 duplication occurred
      after the fungus/animal split, while an independent duplication occurred in
      plants. The proteins encoded by these genes have similar structures, including a
      putative chromodomain close to their N-terminal end and a putative leucine zipper
      at their C-terminus. The possible functional roles of these proteins are
      discussed.

PMID- 10908645
TI  - Efficiencies of fast algorithms of phylogenetic inference under the criteria of
      maximum parsimony, minimum evolution, and maximum likelihood when a large number
      of sequences are used.
AB  - In phylogenetic inference by maximum-parsimony (MP), minimum-evolution (ME), and
      maximum-likelihood (ML) methods, it is customary to conduct extensive heuristic
      searches of MP, ME, and ML trees, examining a large number of different
      topologies. However, these extensive searches tend to give incorrect tree
      topologies. Here we show by extensive computer simulation that when the number of
      nucleotide sequences (m) is large and the number of nucleotides used (n) is
      relatively small, the simple MP or ML tree search algorithms such as the stepwise
      addition (SA) plus nearest neighbor interchange (NNI) search and the SA plus
      subtree pruning regrafting (SPR) search are as efficient as the extensive search
      algorithms such as the SA plus tree bisection-reconnection (TBR) search in
      inferring the true tree. In the case of ME methods, the simple neighbor-joining
      (NJ) algorithm is as efficient as or more efficient than the extensive NJ+TBR
      search. We show that when ME methods are used, the simple p distance generally
      gives better results in phylogenetic inference than more complicated distance
      measures such as the Hasegawa-Kishino-Yano (HKY) distance, even when nucleotide
      substitution follows the HKY model. When ML methods are used, the simple Jukes
      Cantor (JC) model of phylogenetic inference generally shows a better performance
      than the HKY model even if the likelihood value for the HKY model is much higher
      than that for the JC model. This indicates that at least in the present case,
      selecting of a substitution model by using the likelihood ratio test or the AIC
      index is not appropriate. When n is small relative to m and the extent of
      sequence divergence is high, the NJ method with p distance often shows a better
      performance than ML methods with the JC model. However, when the level of
      sequence divergence is low, this is not the case.

PMID- 10908646
TI  - High density of long dinucleotide microsatellites in Drosophila subobscura.
AB  - We isolated 96 dinucleotide repeats with five or more tandemly repeated units
      from a subgenomic Drosophila subobscura library. The mean repeat unit length of
      microsatellite clones in D. subobscura is 15, higher than that observed in other
      Drosophila species. Population variation was assayed in 32-40 chromosomes from
      Barcelona, Spain, using 18 randomly chosen microsatellite loci. Positive
      correlation between measures of variation and perfect repeat length measures
      (mean size, most common, and longest allele) is consistent with a higher mutation
      rate in loci with longer repeat units. Levels of microsatellite variation
      measured as variance in repeat number and heterozygosity in D. subobscura were
      similar to those of Drosophila pseudoobscura and higher than those of Drosophila
      melanogaster and Drosophila simulans. Our data suggest that higher levels of
      microsatellite variation, and possibly density, in D. subobscura compared with D.
      melanogaster are due to both a higher average effective population and a higher
      intrinsic slippage rate in the former species.

PMID- 10908647
TI  - Analysis of intrachromosomal duplications in yeast Saccharomyces cerevisiae: a
      possible model for their origin.
AB  - The complete genome of the yeast Saccharomyces cerevisiae was investigated for
      intrachromosomal duplications at the level of nucleotide sequences. The analysis
      was performed by looking for long approximate repeats (from 30 to 3,885 bp)
      present on each of the chromosomes. We show that direct and inverted repeats
      exhibit very different characteristics: the two copies of direct repeats are more
      similar and longer than those of inverted repeats. Furthermore, contrary to the
      inverted repeats, a large majority of direct repeats appear to be closely spaced.
      The distance (delta) between the two copies is generally smaller than 1 kb.
      Further analysis of these "close direct repeats" shows a negative correlation
      between delta and the percentage of identity between the two copies, and a
      positive correlation between delta and repeat length. Moreover, contrary to the
      other categories of repeats, close direct repeats are mostly located within
      coding sequences (CDSs). We propose two hypotheses in order to interpret these
      observations: first, the deletion/conversion rate is negatively correlated with
      delta; second, there exists an active duplication mechanism which continuously
      creates close direct repeats, the other intrachromosomal repeats being the
      result, by chromosomal rearrangements of these "primary repeats."

PMID- 10908648
TI  - The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles
      are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia
      with a deletion 5q.
AB  - We have isolated the human GRAF gene (for GTPase regulator associated with the
      focal adhesion kinase pp125(FAK)). This gene was fused with MLL in a unique
      t(5;11)(q31;q23) that occurred in an infant with juvenile myelomonocytic
      leukemia. GRAF encodes a member of the Rho family of the GTPase-activating
      protein (GAP) family. On the protein level, it is 90% homologous to the recently
      described chicken GRAF gene that functions as a GAP of RhoA in vivo and is thus a
      critical component of the integrin signaling transduction pathway. The particular
      position of the human GRAF gene at 5q31 and the proposed antiproliferative and
      tumor suppressor properties of its avian homologue suggest that it also might be
      pathogenetically relevant for hematologic malignancies with deletions of 5q. To
      investigate this possibility, we sequenced 4-5 individual cDNA clones from 13
      cases in which one allele of GRAF was deleted. We found point mutations within
      the GAP domain of the second GRAF allele in one patient. In two additional
      patients we found an insertion of 52 or 74 bp within the GRAF cDNA that generates
      a reading frame shift followed by a premature stop codon. GRAF maps outside the
      previously defined commonly deleted 5q31 region. Nevertheless, inactivation of
      both alleles in at least some cases suggests that deletions and mutations of the
      GRAF gene may be instrumental in the development and progression of hematopoeitic
      disorders with a del(5q).

PMID- 10908650
TI  - The molecular basis of vancomycin resistance in clinically relevant Enterococci:
      crystal structure of D-alanyl-D-lactate ligase (VanA).
AB  - d-alanine-d-lactate ligase from Enterococcus faecium BM4147 is directly
      responsible for the biosynthesis of alternate cell-wall precursors in bacteria,
      which are resistant to the glycopeptide antibiotic vancomycin. The crystal
      structure has been determined with data extending to 2.5-A resolution. This
      structure shows that the active site has unexpected interactions and is distinct
      from previous models for d-alanyl-d-lactate ligase mechanistic studies. It
      appears that the preference of the enzyme for lactate as a ligand over d-alanine
      could be mediated by electrostatic effects and/or a hydrogen-bonding network,
      which principally involve His-244. The structure of d-alanyl-d-lactate ligase
      provides a revised interpretation of the molecular events that lead to vancomycin
      resistance.

PMID- 10908649
TI  - A systematic exploration of the influence of the protein stability on amyloid
      fibril formation in vitro.
AB  - There are a number of diseases in which normally soluble proteins associate into
      regular, insoluble amyloid fibrils. The development of in vitro model systems in
      which detailed structural, kinetic, and thermodynamic characterization are
      feasible is of critical importance to our understanding of the amyloid fibril
      phenomenon. The formation of amyloid fibrils by proteins that are not associated
      with disease has been recently described, suggesting that this may be a common
      property of many proteins and not only of the few proteins associated with
      amyloidoses. The B1 Ig-binding domain of protein G (beta1) is an extremely well
      characterized model system. We have found that under certain experimental
      conditions, some variants of beta1 form fibrils with high reproducibility. By
      controlling the stability of the protein-either by mutations or by changing
      experimental conditions-we are able to modulate the ability of the protein to
      form fibrils. For all of the variants, we find that the key requirement for
      fibril formation is to choose conditions in which the population of intermediate
      conformations present during the unfolding transition is maximized.

PMID- 10908651
TI  - Kinetic and thermodynamic control of protein adsorption.
AB  - Control of nonspecific protein adsorption is very important for the design of
      biocompatible and biomimetic materials as well as drug carriers. Grafted polymer
      layers can be used to prevent protein adsorption. We have studied the molecular
      factors that determine the equilibrium and kinetic control of protein adsorption
      by grafted polymer layers. We find that polymers that are not attracted to the
      surface are very effective for kinetic control but not very good for equilibrium
      reduction of protein adsorption. Polymers with attractions to the surface show
      exactly the opposite behavior. The implications for molecular design of
      biocompatible materials also are discussed in this paper.

PMID- 10908652
TI  - Barrier-to-autointegration factor (BAF) bridges DNA in a discrete, higher-order
      nucleoprotein complex.
AB  - Barrier-to-autointegration factor (BAF) is a highly conserved cellular protein
      that was identified by its activity in protecting retroviral DNA against
      autointegration. We show that BAF has the property of bridging double-stranded
      DNA in a highly ordered nucleoprotein complex. Whereas BAF protein alone is a
      dimer in solution, upon binding DNA, BAF forms a dodecamer with DNA bound at
      multiple discrete sites in the complex. The interactions between BAF and DNA are
      entirely nonspecific with respect to DNA sequence. The dual interaction of BAF
      with DNA and LAP2, a protein associated with the nuclear lamina, suggests a role
      for LAP2 in chromosome organization. Consistent with this idea, RNA interference
      experiments with Caenorhabditis elegans reveal a defect in mitosis.

PMID- 10908654
TI  - The pleiotropic response regulator DegU functions as a priming protein in
      competence development in Bacillus subtilis.
AB  - The response regulator DegU is involved in various late-growth developmental
      processes in Bacillus subtilis, including the production of degradative enzymes
      and the development of genetic competence. DegU is essential for the expression
      of the competence transcription factor, encoded by comK. ComK is required for the
      transcription of genes encoding the DNA uptake and integration machinery, as well
      as for the transcription of its own gene. We have purified DegU to study its role
      in the expression of comK, and we demonstrate here that DegU binds specifically
      to the comK promoter. The binding of the response regulator DegU to a promoter
      target had not been reported previously. DNase I protection analyses show that
      the DegU binding site overlaps with the ComK binding site, and gel retardation
      experiments indicate that DegU strongly stimulates the binding of ComK to the
      comK promoter. We propose that DegU functions at the initiation of competence
      development, when ComK concentrations are insufficient to support comK
      transcription, by facilitating ComK binding to the comK promoter. DegU therefore
      acts as a priming protein that primes the autostimulatory transcription of comK.
      Such priming activity adds a function to the class of response regulator
      proteins.

PMID- 10908653
TI  - Subnucleus-specific loss of neurons in medial thalamus of schizophrenics.
AB  - The hypoactivity of dorsolateral prefrontal cortex in schizophrenics is well
      known. One cause of this hypoactivity may be defective corticocortical or
      thalamocortical connections. Recent imaging studies of the thalamus suggest
      reductions in volume of the whole thalamus and reduced activity in the medial
      group of thalamic nuclei, which may indicate loss of functional input to the
      cortex. Using stereological techniques in six pairs of individually matched
      brains from schizophrenics and controls, we measured the volumes and obtained
      estimates of the number of neurons in the three subnuclei (parvocellular, pc;
      densocellular, dc; magnocellular, mc) of the mediodorsal nucleus (MD) and from
      the ventral posterior medial nucleus. There was a significant reduction in total
      neuron number in MD as a whole but this neuron loss was largely restricted to
      MDpc and MDdc [-30.9 and -24.5%, respectively (P </= 0.01)]. MDmc and the control
      ventral posterior medial nucleus showed no significant changes in cell number.
      Because the subnuclei of MD have different connections and project to different
      areas of the frontal cortex, the specific loss of neurons in MDpc and MDdc has
      implications for the functional defects observed in schizophrenia.

PMID- 10908655
TI  - Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell
      cycle arrest in human breast cancer cells.
AB  - Estrogens and antiestrogens influence the G(1) phase of the cell cycle. In MCF-7
      breast cancer cells, estrogen stimulated cell cycle progression through loss of
      the kinase inhibitor proteins (KIPs) p27 and p21 and through G(1) cyclin
      dependent kinase (cdk) activation. Treatment with antiestrogen drugs, Tamoxifen
      or ICI 182780, caused cell cycle arrest, with up-regulation of both p21 and p27
      levels, an increase in their binding to cyclin E-cdk2, and kinase inhibition. The
      requirement for these KIPs in the arrests induced by estradiol depletion or by
      antiestrogens was investigated with antisense. Antisense inhibition of p21 or p27
      expression in estradiol-depleted or antiestrogenarrested MCF-7 led to abrogation
      of cell cycle arrest, with loss of cyclin E-associated KIPs, activation of cyclin
      E-cdk2, and S phase entrance. These data demonstrate that depletion of either p21
      or p27 can mimic estrogen-stimulated cell cycle activation and indicate that both
      of these KIPs are critical mediators of the therapeutic effects of antiestrogens
      in breast cancer.

PMID- 10908656
TI  - Molecular basis of protein kinase C-induced activation of ATP-sensitive potassium
      channels.
AB  - Potassium channels that are inhibited by internal ATP (K(ATP) channels) provide a
      critical link between metabolism and cellular excitability. Protein kinase C
      (PKC) acts on K(ATP) channels to regulate diverse cellular processes, including
      cardioprotection by ischemic preconditioning and pancreatic insulin secretion.
      PKC action decreases the Hill coefficient of ATP binding to cardiac K(ATP)
      channels, thereby increasing their open probability at physiological ATP
      concentrations. We show that PKC similarly regulates recombinant channels from
      both the pancreas and heart. Surprisingly, PKC acts via phosphorylation of a
      specific, conserved threonine residue (T180) in the pore-forming subunit
      (Kir6.2). Additional PKC consensus sites exist on both Kir and the larger
      sulfonylurea receptor (SUR) subunits. Nonetheless, T180 controls changes in open
      probability induced by direct PKC action either in the absence of, or in complex
      with, the accessory SUR1 (pancreatic) or SUR2A (cardiac) subunits. The high
      degree of conservation of this site among different K(ATP) channel isoforms
      suggests that this pathway may have wide significance for the physiological
      regulation of K(ATP) channels in various tissues and organelles.

PMID- 10908657
TI  - Snapshots of usher-mediated protein secretion and ordered pilus assembly.
AB  - Type 1 pilus biogenesis was used as a paradigm to investigate ordered
      macromolecular assembly at the outer cell membrane. The ability of Gram-negative
      bacteria to secrete proteins across their outer membrane and to assemble adhesive
      macromolecular structures on their surface is a defining event in pathogenesis.
      We elucidated genetic, biochemical, and biophysical requirements for assembly of
      functional type 1 pili. We discovered that the minor pilus protein FimG plays a
      critical role in nucleating the formation of the adhesive tip fibrillum. Genetic
      methods were used to trap pilus subunits during their translocation through the
      outer membrane usher protein, providing data on the structural interactions that
      occur between subunit components during type 1 pilus formation. Electron
      microscopic and biochemical analyses of these stepwise assembly intermediates
      demonstrated that translocation of pilus subunits occurs linearly through the
      usher's central channel, with formation of the pilus helix occurring
      extracellularly. Specialized pilin subunits play unique roles both in this
      multimerization and in the final ultrastructure of the adhesive pilus.

PMID- 10908658
TI  - Trans catalysis in Tn5 transposition.
AB  - Synaptic complexes in prokaryotic transposons occur when transposase monomers
      bind to each of two specific end-binding sequences and then associate to bring
      the proteins and the two ends of the transposon together. It is within this
      complex of proteins and DNA that identical catalytic reactions are carried out by
      transposase on each of the ends of the transposon. In this study, we perform in
      vitro transposition reactions by combining the methylated inside end (IE(ME))
      biased hyperactive Tn5 transposase, Tnp sC7 version 2.0, and the outside end (OE)
      biased hyperactive Tn5 transposase, Tnp EK/LP, with plasmid DNA containing a
      transposon defined by one IE(ME) and one OE. These two proteins cooperate to
      facilitate double end cleavage of the transposon from the plasmid and conversion
      into transposition products via strand transfer. When one of the hyperactive Tnps
      is replaced with a catalytically inactive version containing the mutation EA326
      (DDE mutant), the predominant reaction product is a linearized plasmid resulting
      from single end cleavage. Restriction analysis of these linear products reveals
      that cleavage is occurring on the end distal to that which is bound by the
      transposase with an intact active site or in trans. Similar in vitro experiments
      performed with precut transposons and a supercoiled target plasmid demonstrated
      that the strand transfer reaction is also facilitated by a trans active DDE
      motif.

PMID- 10908659
TI  - Specific binding sites for alcohols and anesthetics on ligand-gated ion channels.
AB  - Ligand-gated ion channels are a target for inhaled anesthetics and alcohols in
      the central nervous system. The inhibitory strychnine-sensitive glycine and gamma
      aminobutyric acid type A receptors are positively modulated by anesthetics and
      alcohols, and site-directed mutagenesis techniques have identified amino acid
      residues important for the action of volatile anesthetics and alcohols in these
      receptors. A key question is whether these amino acids are part of an
      alcohol/anesthetic-binding site. In the present study, we used an alkanethiol
      anesthetic to covalently label its binding site by mutating selected amino acids
      to cysteine. We demonstrated that the anesthetic propanethiol, or alternatively,
      propyl methanethiosulfonate, covalently binds to cysteine residues introduced
      into a specific second transmembrane site in glycine receptor and gamma
      aminobutyric acid type A receptor subunits and irreversibly enhances receptor
      function. Moreover, upon permanent occupation of the site by propyl disulfide,
      the usual ability of octanol, enflurane, and isoflurane to potentiate the
      function of the ion channels was lost. This approach provides strong evidence
      that the actions of anesthetics in these receptors are due to binding at a single
      site.

PMID- 10908661
TI  - A chromatin insulator protects retrovirus vectors from chromosomal position
      effects.
AB  - Recombinant murine retroviruses are widely used as delivery vectors for gene
      therapy. However, once integrated into a chromosome, these vectors often suffer
      from profound position effects, with vector silencing observed in vitro and in
      vivo. To overcome this problem, we investigated whether the HS4 chromatin
      insulator from the chicken beta-globin locus control region could protect a
      retrovirus vector from position effects. When used to flank a reporter vector,
      this element significantly increased the fraction of transduced cells that
      expressed the provirus in cultures and in mice transplanted with transduced
      marrow. These results demonstrate that a chromatin insulator can improve the
      expression performance of a widely used class of gene therapy vectors by
      protecting these vectors from chromosomal position effects.

PMID- 10908660
TI  - A dual role for the kinase-like domain of the tyrosine kinase Tyk2 in interferon
      alpha signaling.
AB  - Tyrosine kinases of the Janus kinase family initiate cellular responses through
      their association with receptors for alpha-helical cytokines. In addition to a
      tyrosine kinase domain, these enzymes possess a kinase-like (KL) domain, whose
      function remains elusive. To investigate the role of the KL domain of Tyk2 in
      interferon-alpha/beta signaling, we transfected a library of Tyk2 cDNAs
      containing random point mutations in KL into Tyk2-negative cells and selected for
      loss-of-function Tyk2 mutants. Four such mutants, V584D, G596V, H669P, and R856G,
      were identified through this screen. Like the wild-type Tyk2, the mutant proteins
      were able to sustain the level of IFNAR1 receptor protein. However, all four
      mutants were incapable of restoring high-affinity interferon-alpha binding in
      Tyk2-negative cells and were also catalytically impaired, even when transiently
      overexpressed. Interferon-alpha induced phosphorylation, and gene expression
      could be detected in V584D- or G596V-expressing cells, but not in H669P- or R856G
      expressing cells. Furthermore, H669P and R856G proteins were constitutively
      highly phosphorylated. All together, our findings demonstrate that an intact KL
      domain is essential for the intrinsic catalytic activity of Tyk2 and for the
      establishment of a high-affinity interferon-alpha receptor complex.

PMID- 10908662
TI  - Coreceptor restriction within the HLA-DQ locus for Epstein-Barr virus infection.
AB  - Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that causes infectious
      mononucleosis and is etiologically associated with malignancies of multiple
      origins. EBV enters cells through a cascade of interactions between its envelope
      glycoprotein gp350 and the gp42-gH-gL complex with cellular receptors. Membrane
      fusion is catalyzed by the binding of gp42, a member of the C type lectin family,
      to HLA class II molecule HLA-DR, -DP, or -DQ. Here we demonstrate that only a
      subset of HLA-DQ alleles mediates EBV entry, indicating that individuals
      expressing these alleles may offer unique sites for EBV infection and subsequent
      sequelae. Additionally, the specific site within HLA-DQ determined to be
      essential for EBV entry is homologous to a site within MHC class I shown by
      structural studies to bind to the C type-lectin-like natural killer receptor,
      providing insight into the biochemical nature of the gp42-HLA class II
      interaction.

PMID- 10908663
TI  - B cell maturation protein is a receptor for the tumor necrosis factor family
      member TALL-1.
AB  - TALL-1 is a recently identified member of the tumor necrosis factor (TNF) family
      that costimulates B lymphocyte proliferation. Here we show that B cell maturation
      protein (BCMA), a member of the TNF receptor family that is expressed only by B
      lymphocytes, specifically binds to TALL-1. A soluble receptor containing the
      extracellular domain of BCMA blocks the binding of TALL-1 to its receptor on the
      plasma membrane and inhibits TALL-1-triggered B lymphocyte costimulation.
      Overexpression of BCMA activates NF-kappaB, and this activation is potentiated by
      TALL-1. Moreover, BCMA-mediated NF-kappaB activation is inhibited by dominant
      negative mutants of TNF receptor-associated factor 5 (TRAF5), TRAF6, NF-kappaB
      inducing kinase (NIK), and IkappaB kinase (IKK). These data indicate that BCMA is
      a receptor for TALL-1 and BCMA activates NF-kappaB through a TRAF5-, TRAF6-, NIK
      , and IKK-dependent pathway. The identification of BCMA as a NF-kappaB-activating
      receptor for TALL-1 suggests molecular targets for drug development against
      certain immunodeficient or autoimmune diseases.

PMID- 10908664
TI  - Inactivation of wild-type p53 tumor suppressor by electrophilic prostaglandins.
AB  - The electrophilic eicosanoids prostaglandins A(1) or A(2) impaired p53-dependent
      transcription of endogenous genes and exogenous p53-luciferase reporter plasmids
      in RKO and HCT 116 colon cancer cells. Cellular accumulation of genetically wild
      type, but transcriptionally silent p53 varied as a function of exposure time and
      concentration of prostaglandins A(1) and A(2). Prostaglandins A(1) and A(2)
      induced a conformational change in wild-type p53 that corresponded with its
      inactivation and its aberrant redistribution from the cytosol to the nucleus.
      Derangement of its transcriptional activity manifested as inhibition of p53
      mediated apoptosis by etoposide, a representative antineoplastic agent. We
      conclude that electrophilic eicosanoids impair the role of wild-type p53 as a
      guardian of genomic integrity by a process distinct from somatic mutation or
      viral oncoprotein binding. This process may pertain to malignant and premalignant
      conditions, such as colon carcinoma and adenoma, which often harbor a genetically
      wild-type, but inactive form of p53 tumor suppressor.

PMID- 10908665
TI  - Thermodynamic characterization of the interaction between TRAF2 and tumor
      necrosis factor receptor peptides by isothermal titration calorimetry.
AB  - The tumor necrosis factor receptor (TNFR) superfamily can induce diverse
      biological effects, including cell survival, proliferation, differentiation, and
      apoptosis. The major signal transducers for TNFRs are the family of TNF receptor
      associated factors (TRAFs). The direct interaction between TRAFs and the
      intracellular tails of TNFRs is the first step of this signal relay process.
      Structural studies have revealed a trimeric nature of TRAF2 and a symmetrical
      mode of receptor binding, suggesting the involvement of trivalent TNFR2-receptor
      interaction in the signal transduction. In this study, using isothermal titration
      calorimetry (ITC), we report thermodynamic characterization of the interaction
      between TRAF2 and monomeric peptide sequences from TNFR members, including TNFR2,
      CD40, CD30, Ox40, and 4-1BB, and the Epstein-Barr virus (EBV)-transforming
      protein, latent infection membrane protein-1 (LMP1). The dissociation constants
      of the interaction were shown to range between 40 microM and 1.9 mM, which are
      substantially weaker than most protein-peptide interactions. The interaction is
      entirely driven by exothermic enthalpy, consistent with the abundance of polar
      contacts. The enthalpy of the interaction has a significant temperature
      dependence (DeltaCp = -245 cal/mol small middle dotK). The unfavorable entropy in
      the interaction and the comparison with structural energetics calculations
      suggest the involvement of conformational rearrangement in the interaction. The
      low affinity of TRAF2 to monomeric receptor peptides further supports the
      importance of avidity contribution in TRAF2 recruitment by these receptors upon
      ligand-induced trimerization or higher order oligomerization.

PMID- 10908666
TI  - Recognition of the 300-kDa mannose 6-phosphate receptor cytoplasmic domain by 47
      kDa tail-interacting protein.
AB  - Tail-interacting 47-kDa protein (TIP47) binds the cytoplasmic domains of the
      cation-dependent (CD) and cation-independent (CI) mannose 6-phosphate receptors
      (MPRs) and is required for their transport from endosomes to the Golgi complex.
      TIP47 recognizes a phenylalanine-tryptophan signal in the CD-MPR. We show here
      that TIP47 interaction with the 163-residue CI-MPR cytoplasmic domain is highly
      conformation dependent and requires CI-MPR residues that are proximal to the
      membrane. CI-MPR cytoplasmic domain residues 1-47 are dispensable, whereas
      residues 48-74 are essential for high-affinity binding. However, residues 48-74
      are not sufficient for high-affinity binding; residues 75-163 alone display weak
      affinity for TIP47, yet they contribute to the presentation of residues 48-74 in
      the intact protein. Independent competition binding experiments confirm that
      TIP47 interacts with the membrane-proximal portion of the CI-MPR cytoplasmic
      domain. TIP47 binding is competed by the binding of the AP-2 clathrin adaptor at
      (and near) residues 24-29 but not by AP-1 binding at (and near) residues 160-161.
      Finally, TIP47 appears to recognize a putative loop generated by the sequence
      PPAPRPG and other hydrophobic residues in the membrane-proximal domain. Although
      crystallography will be needed to define the precise interaction interface, these
      data provide an initial structural basis for TIP47-CI-MPR association.

PMID- 10908667
TI  - Rapid mapping of protein functional epitopes by combinatorial alanine scanning.
AB  - A combinatorial alanine-scanning strategy was used to determine simultaneously
      the functional contributions of 19 side chains buried at the interface between
      human growth hormone and the extracellular domain of its receptor. A phage
      displayed protein library was constructed in which the 19 side chains were
      preferentially allowed to vary only as the wild type or alanine. The library pool
      was subjected to binding selections to isolate functional clones, and DNA
      sequencing was used to determine the alanine/wild-type ratio at each varied
      position. This ratio was used to calculate the effect of each alanine
      substitution as a change in free energy relative to that of wild type. Only seven
      side chains contribute significantly to the binding interaction, and these
      conserved residues form a compact cluster in the human growth hormone tertiary
      structure. The results were in excellent agreement with free energy data
      previously determined by conventional alanine-scanning mutagenesis and suggest
      that this technology should be useful for analyzing functional epitopes in
      proteins.

PMID- 10908668
TI  - In vivo immunological function of mast cells derived from embryonic stem cells:
      an approach for the rapid analysis of even embryonic lethal mutations in adult
      mice in vivo.
AB  - An important goal of tissue engineering is to achieve reconstitution of specific
      functionally active cell types by transplantation of differentiated cell
      populations derived from normal or genetically altered embryonic stem cells in
      vitro. We find that mast cells derived in vitro from wild-type or genetically
      manipulated embryonic stem cells can survive and orchestrate immunologically
      specific IgE-dependent reactions after transplantation into mast cell-deficient
      Kit(W)/Kit(W-v) mice. These findings define a unique approach for analyzing the
      effects of mutations of any genes that are expressed in mast cells, including
      embryonic lethal mutations, in vitro or in vivo.

PMID- 10908669
TI  - The development of fatal myocarditis and polymyositis in mice heterozygous for
      IFN-gamma and lacking the SOCS-1 gene.
AB  - Mice lacking the gene encoding the suppressor of cytokine signaling-1 (SOCS-1 -/
      ) and heterozygous for the IFN-gamma gene (IFN-gamma +/-) avoided the IFN-gamma
      dependent preweaning death of SOCS-1 -/- IFN-gamma +/+ mice but did not exhibit
      the good health of young adult SOCS-1 -/- IFN-gamma -/- mice. SOCS-1 -/- IFN
      gamma +/- mice died within 160 days of birth with massive T lymphocyte,
      macrophage, and eosinophil infiltration of all skeletal muscles and a similar
      severe myocarditis. The cornea also developed inflammatory infiltration and often
      a corneal ulcer. The mice exhibited evidence of selective CD8 T lymphocyte
      activation in populations in the thymus, spleen, and lymph nodes and focal T- and
      B-lymphoid infiltrates developed in the lung and salivary gland without apparent
      tissue damage. Comparison of SOCS-1 -/- IFN-gamma +/- mice with various control
      mice indicated that the development of tissue-damaging T lymphocyte, macrophage,
      and eosinophil infiltrates required loss of SOCS-1 and the presence of some IFN
      gamma, but that the lung lymphoid infiltrates required only loss of SOCS-1 to
      develop.

PMID- 10908670
TI  - Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in
      the protozoan parasite Leishmania major.
AB  - Protozoan parasites of the genus Leishmania undergo a complex life cycle
      involving transmission by biting sand flies and replication within mammalian
      macrophage phagolysosomes. A major component of the Leishmania surface coat is
      the glycosylphosphatidylinositol (GPI)-anchored polysaccharide called
      lipophosphoglycan (LPG). LPG has been proposed to play many roles in the
      infectious cycle, including protection against complement and oxidants, serving
      as the major ligand for macrophage adhesion, and as a key factor mitigating host
      responses by deactivation of macrophage signaling pathways. However, all
      structural domains of LPG are shared by other major surface or secretory
      products, providing a biochemical redundancy that compromises the ability of in
      vitro tests to establish whether LPG itself is a virulence factor. To study truly
      lpg(-) parasites, we generated Leishmania major lacking the gene LPG1 [encoding a
      putative galactofuranosyl (Gal(f)) transferase] by targeted gene disruption. The
      lpg1(-) parasites lacked LPG but contained normal levels of related
      glycoconjugates and GPI-anchored proteins. Infections of susceptible mice and
      macrophages in vitro showed that these lpg(-) Leishmania were highly attenuated.
      Significantly and in contrast to previous LPG mutants, reintroduction of LPG1
      into the lpg(-) parasites restored virulence. Thus, genetic approaches allow
      dissection of the roles of this complex family of interrelated parasite virulence
      factors, and definitively establish the role of LPG itself as a parasite
      virulence factor. Because the lpg1(-) mutant continue to synthesize bulk GPI
      anchored Gal(f)-containing glycolipids other than LPG, a second pathway distinct
      from the Golgi-associated LPG synthetic compartment must exist.

PMID- 10908671
TI  - Hormone binding induces rapid proteasome-mediated degradation of thyroid hormone
      receptors.
AB  - The thyroid hormone 3,3',5-triiodo-l-thyronine (T3) is essential for growth,
      differentiation, and development. Its biological activities are mediated by T3
      nuclear receptors (TRs). At present, how T3 regulates TR proteins and the
      resulting functional consequences are still unknown. Immunofluorescence analyses
      of endogenous TR in the growth hormone-producing GC cells showed that the T3
      induced rapid degradation of TR was specifically blocked by lactacystin, a
      selective inhibitor of the ubiquitin-proteasome degradation pathway. Immunoblots
      demonstrated that the transfected TRbeta1 was ubiquitinated and that the
      ubiquitination was T3 independent. Studies with a series of truncated TRbeta1
      showed that the hormone-binding domain was sufficient for the T3-induced rapid
      degradation of TRbeta1 by the proteasome degradation pathway. T3 also induced
      rapid degradation of TRbeta2 and TRalpha1. In contrast, the stability of the non
      T3-binding TRalpha2 and naturally occurring TRbeta1 mutants that do not bind T3
      was not affected by T3 treatment, indicating that hormone binding to receptor was
      essential for the degradation of the wild-type receptors. In the presence of
      proteasome protease inhibitors, the levels of both total and ubiquitinated
      TRbeta1 protein increased, yet T3-dependent transcriptional activation and the
      expression of the growth hormone gene were diminished, suggesting that proteasome
      mediated degradation played a novel role in modulating transcriptional activation
      by TR. The present study reveals a role of T3 in modulating the functions of TR
      by regulating its receptor level via the ubiquitin-proteasome degradation
      pathway.

PMID- 10908672
TI  - Engineering blood meal-activated systemic immunity in the yellow fever mosquito,
      Aedes aegypti.
AB  - Progress in molecular genetics makes possible the development of alternative
      disease control strategies that target the competence of mosquitoes to transmit
      pathogens. We tested the regulatory region of the vitellogenin (Vg) gene of Aedes
      aegypti for its ability to express potential antipathogen factors in transgenic
      mosquitoes. Hermes-mediated transformation was used to integrate a 2.1-kb Vg
      promoter fragment driving the expression of the Defensin A (DefA) coding region,
      one of the major insect immune factors. PCR amplification of genomic DNA and
      Southern blot analyses, carried out through the ninth generation, showed that the
      Vg-DefA transgene insertion was stable. The Vg-DefA transgene was strongly
      activated in the fat body by a blood meal. The mRNA levels reached a maximum at
      24-h postblood meal, corresponding to the peak expression time of the endogenous
      Vg gene. High levels of transgenic defensin were accumulated in the hemolymph of
      bloodfed female mosquitoes, persisting for 20-22 days after a single blood
      feeding. Purified transgenic defensin showed antibacterial activity comparable to
      that of defensin isolated from bacterially challenged control mosquitoes. Thus,
      we have been able to engineer the genetically stable transgenic mosquito with an
      element of systemic immunity, which is activated through the blood meal-triggered
      cascade rather than by infection. This work represents a significant step toward
      the development of molecular genetic approaches to the control of vector
      competence in pathogen transmission.

PMID- 10908673
TI  - Speeding molecular recognition by using the folding funnel: the fly-casting
      mechanism.
AB  - Protein folding and binding are kindred processes. Many proteins in the cell are
      unfolded, so folding and function are coupled. This paper investigates how
      binding kinetics is influenced by the folding of a protein. We find that a
      relatively unstructured protein molecule can have a greater capture radius for a
      specific binding site than the folded state with its restricted conformational
      freedom. In this scenario of binding, the unfolded state binds weakly at a
      relatively large distance followed by folding as the protein approaches the
      binding site: the "fly-casting mechanism." We illustrate this scenario with the
      hypothetical kinetics of binding a single repressor molecule to a DNA site and
      find that the binding rate can be significantly enhanced over the rate of binding
      of a fully folded protein.

PMID- 10908674
TI  - Modulation of CTP:phosphocholine cytidylyltransferase by membrane curvature
      elastic stress.
AB  - The activity of CTP:phosphocholine cytidylyltransferase, a rate-limiting enzyme
      in phosphatidylcholine biosynthesis, is modulated by its interaction with lipid
      bilayers [Kent, C. (1997) Biochim. Biophys. Acta 1348, 79-90]. Its regulation is
      of central importance in the maintenance of membrane lipid homeostasis. Here we
      show evidence that the stored curvature elastic stress in the lipid membrane's
      monolayer modulates the activity of CTP:phosphocholine cytidylyltransferase. Our
      results show how a purely physical feedback signal could play a key role in the
      control of membrane lipid synthesis.

PMID- 10908676
TI  - Learning about pain: the neural substrate of the prediction error for aversive
      events.
AB  - Associative learning is thought to depend on detecting mismatches between actual
      and expected experiences. With functional magnetic resonance imaging (FMRI), we
      studied brain activity during different types of mismatch in a paradigm where
      contrasting-colored lights signaled the delivery of painful heat, nonpainful
      warmth, or no stimulation. When painful heat stimulation was unexpected, there
      was increased FMRI signal intensity in areas of the hippocampus, superior frontal
      gyrus, cerebellum, and superior parietal gyrus that was not found with mismatch
      between expectation and delivery of nonpainful warmth stimulation. When painful
      heat stimulation was unexpectedly omitted, the FMRI signal intensity decreased in
      the left superior parietal gyrus and increased in the other regions. These
      contrasting activation patterns correspond to two different mismatch concepts in
      theories of associative learning (Rescorla-Wagner, temporal difference vs. Pearce
      Hall, Mackintosh). Searching for interventions to specifically modulate
      activation of these brain regions therefore offers an approach to identifying new
      treatments for chronic pain, which often has a substantial associative learning
      component.

PMID- 10908675
TI  - The cysteine desulfurase, IscS, has a major role in in vivo Fe-S cluster
      formation in Escherichia coli.
AB  - The cysteine desulfurase, IscS, provides sulfur for Fe-S cluster synthesis in
      vitro, but a role for IscS in in vivo Fe-S cluster formation has yet to be
      established. To study the in vivo function of IscS in Escherichia coli, a strain
      lacking IscS was constructed and characterized. Using this iscS deletion strain,
      we have observed decreased specific activities for proteins containing [4Fe-4S]
      clusters from soluble (aconitase B, 6-phosphogluconate dehydratase, glutamate
      synthase, fumarase A, and FNR) and membrane-bound proteins (NADH dehydrogenase I
      and succinate dehydrogenase). A specific role for IscS in in vivo Fe-S cluster
      assembly was demonstrated by showing that an Fe-S cluster independent mutant of
      FNR is unaffected by the lack of IscS. These data support the conclusion that,
      via its cysteine desulfurase activity, IscS provides the sulfur that subsequently
      becomes incorporated during in vivo Fe-S cluster synthesis. We also have
      characterized a growth phenotype associated with the loss of IscS. Under aerobic
      conditions the deletion of IscS caused an auxotrophy for thiamine and nicotinic
      acid, whereas under anaerobic conditions, only nicotinic acid was required. The
      lack of IscS also had a general effect on the growth of E. coli because the iscS
      deletion strain grew at half the rate of wild type in many types of media even
      when the auxotrophies were satisfied.

PMID- 10908677
TI  - Protein-interaction modules that organize nuclear function: FF domains of CA150
      bind the phosphoCTD of RNA polymerase II.
AB  - An approach for purifying nuclear proteins that bind directly to the
      hyperphosphorylated C-terminal repeat domain (CTD) of RNA polymerase II was
      developed and used to identify one human phosphoCTD-associating protein as CA150.
      CA150 is a nuclear factor implicated in transcription elongation. Because the
      hyperphosphorylated CTD is a feature of actively transcribing RNA polymerase II
      (Pol II), phosphoCTD (PCTD) binding places CA150 in a location appropriate for
      performing a role in transcription elongation-related events. Several recombinant
      segments of CA150 bound the PCTD. Predominant binding is mediated by the portion
      of CA150 containing six FF domains, compact modules of previously unknown
      function. In fact, small recombinant proteins containing the fifth FF domain
      bound the PCTD. PCTD binding is the first specific function assigned to an FF
      domain. As FF domains are found in a variety of nuclear proteins, it is likely
      that some of these proteins are also PCTD-associating proteins. Thus FF domains
      appear to be compact protein-interaction modules that, like WW domains, can be
      evolutionarily shuffled to organize nuclear function.

PMID- 10908678
TI  - A new role for a SNARE protein as a regulator of the Ypt7/Rab-dependent stage of
      docking.
AB  - The homotypic fusion of yeast vacuoles occurs in an ordered cascade of priming,
      docking, and fusion. The linkage between these steps has so far remained unclear.
      We now report that Vam7p (the vacuolar SNAP-23/25 homolog) signals from the cis
      SNARE complex to Ypt7p (the vacuolar Rab/Ypt) to initiate the docking process.
      After Vam7p has been released from the cis-SNARE complex by Sec18p-mediated
      priming, it is still required for Ypt7p-dependent docking and it needs Ypt7p to
      remain on the vacuole. Thus, after priming, Vam7p is released from the vacuole
      altogether if Ypt7p has been extracted by Gdi1p or inactivated by antibody but is
      not released if docking is blocked simply by vacuole dilution; it is therefore
      Ypt7p function, and not docking per se, that retains Vam7p. In accord with this
      finding, cells deleted for the gene encoding Ypt7 have normal amounts of Vam7p
      but have little Vam7p on their isolated vacuoles. Interaction of Vam7p and Ypt7p
      is further indicated by two-hybrid analysis [Uetz, P., Giot, L., Cagney, G.,
      Mansfield, T. A., Judson, R. S., Knight, J. R., Lockshon, D., Narayan, V.,
      Srinivasan, M., Pochart, P., et al. (2000) Nature (London) 403, 623-627] and by
      the effect of Vam7p on the association of the Rab/Ypt-effector HOPS complex
      (homotypic fusion and vacuole protein sorting; Vam2p and Vam6p plus four vacuole
      protein sorting class C proteins) with Ypt7p. Vam7p provides a functional link
      between the priming step, which releases it from the cis-SNARE complex, and
      docking.

PMID- 10908679
TI  - Crystal structure of Escherichia coli CyaY protein reveals a previously
      unidentified fold for the evolutionarily conserved frataxin family.
AB  - Friedreich ataxia is an autosomal recessive neurodegenerative disease caused by
      defects in the FRDA gene, which encodes a mitochondrial protein called frataxin.
      Frataxin is evolutionarily conserved, with homologs identified in mammals, worms,
      yeast, and bacteria. The CyaY proteins of gamma-purple bacteria are believed to
      be closely related to the ancestor of frataxin. In this study, we have determined
      the crystal structure of the CyaY protein from Escherichia coli at 1.4-A
      resolution. It reveals a protein fold consisting of a six-stranded antiparallel
      beta-sheet flanked on one side by two alpha-helices. This fold is likely to be
      shared by all members of the conserved frataxin family. This study also provides
      a framework for the interpretation of disease-associated mutations in frataxin
      and for understanding the possible functions of this protein family.

PMID- 10908680
TI  - Comparing sequenced segments of the tomato and Arabidopsis genomes: large-scale
      duplication followed by selective gene loss creates a network of synteny.
AB  - A 105-kilobase bacterial artificial chromosome (BAC) clone from the ovate
      containing region of tomato chromosome 2 was sequenced and annotated. The tomato
      BAC sequence was then compared, gene by gene, with the sequenced portions of the
      Arabidopsis thaliana genome. Rather than matching a single portion of the
      Arabidopsis genome, the tomato clone shows conservation of gene content and order
      with four different segments of Arabidopsis chromosomes 2-5. The gene order and
      content of these individual Arabidopsis segments indicate that they derived from
      a common ancestral segment through two or more rounds of large-scale genome
      duplication events-possibly polyploidy. One of these duplication events is
      ancient and may predate the divergence of the Arabidopsis and tomato lineages.
      The other is more recent and is estimated to have occurred after the divergence
      of tomato and Arabidopsis approximately 112 million years ago. Together, these
      data suggest that, on the scale of BAC-sized segments of DNA, chromosomal
      rearrangements (e.g., inversions and translocations) have been only a minor
      factor in the divergence of genome organization among plants. Rather, the
      dominating factors have been repeated rounds of large-scale genome duplication
      followed by selective gene loss. We hypothesize that these processes have led to
      the network of synteny revealed between tomato and Arabidopsis and predict that
      such networks of synteny will be common when making comparisons among higher
      plant taxa (e.g., families).

PMID- 10908681
TI  - Selective inhibition of HIV replication in primary macrophages but not T
      lymphocytes by macrophage-derived chemokine.
AB  - Macrophage-derived chemokine (MDC) has been reported to inhibit different HIV-1
      strains in activated peripheral blood mononuclear cells (T cell blasts), although
      other investigators have not confirmed these findings. Here we demonstrate that
      MDC inhibits the replication of CCR5-dependent (R5) HIV-1(BaL) in monocyte
      derived macrophages (MDM), but not in T cell blasts, although with variable
      potency depending on donor variability. Analysis of HIV-1(BaL) proviral DNA
      synthesis in MDM indicated that the suppressive effect of MDC did not involve
      inhibition of early events such as entry or reverse transcription. Finally, an
      inverse correlation was observed between the levels of endogenous MDC secreted by
      uninfected MDM of different donors and the efficiency of different HIV strains,
      including two primary isolates with different coreceptor usage, to replicate in
      these cells. Thus, MDC represents an example of a chemokine inhibiting HIV
      replication in macrophages acting at one or more postentry levels in the virus
      life cycle.

PMID- 10908683
TI  - Leflunomide, a new disease-modifying anti-rheumatic drug and the never ending
      rheumatoid arthritis story.

PMID- 10908682
TI  - Neuroprotective potential of a viral vector system induced by a neurological
      insult.
AB  - Gene transfer into neurons via viral vectors for protection against acute
      necrotic insults has generated considerable interest. Most studies have used
      constitutive vector systems, limiting the ability to control transgene expression
      in a dose-dependent, time-dependent, or reversible manner. We have constructed
      defective herpes simplex virus vectors designed to be induced by necrotic
      neurological insults themselves. Such vectors contain a synthetic glucocorticoid
      responsive promoter, taking advantage of the almost uniquely high levels of
      glucocorticoids-adrenal stress steroids-secreted in response to such insults. We
      observed dose-responsive and steroid-specific induction by endogenous and
      synthetic glucocorticoids in hippocampal cultures. Induction was likely to be
      rapid enough to allow transgenic manipulation of relatively early steps in the
      cascade of necrotic neuron death. The protective potential of such a vector was
      tested by inclusion of a neuroprotective transgene (the Glut-1 glucose
      transporter). Induction of this vector by glucocorticoids decreased glutamatergic
      excitotoxicity in culture. Finally, both exogenous glucocorticoids and
      excitotoxic seizures induced reporter gene expression driven from a
      glucocorticoid-responsive herpes simplex virus vector in the hippocampus in vivo.

PMID- 10908684
TI  - Reflex sympathetic dystrophy.

PMID- 10908685
TI  - T-cell trafficking into sites of inflammation.

PMID- 10908686
TI  - Magnetic resonance imaging in early inflammatory arthritis: what is its role?
AB  - Magnetic resonance imaging (MRI) has important applications in musculoskeletal
      medicine. It allows the visualization of bone and soft tissues in three
      dimensions using a multiplanar technique and is uniquely suited to imaging the
      rheumatoid joint. Bony erosions are seen well using MRI in early rheumatoid
      arthritis and are frequently detected before they appear on plain radiographs.
      Bone marrow oedema is another important MRI feature associated with inflammatory
      joint disease and may be a forerunner of erosion. Synovial membrane inflammation
      and hypertrophy are detected after contrast enhancement and also by the use of
      dynamic MRI techniques, which provide a non-invasive method to accurately measure
      the inflammatory process. This information can be analysed and collated using MRI
      scoring systems and ultimately may be used to improve diagnostic accuracy,
      predict prognosis and monitor therapy in these patients. This review examines the
      case for the use of MRI in early inflammatory arthritis, outlining its strengths
      and potential weaknesses as an imaging modality in this context and indicating
      its potential role in clinical practice.

PMID- 10908687
TI  - Calcium metabolism in sarcoidosis and its clinical implications.
AB  - OBJECTIVE: : To examine the clinical implications of disturbed calcium metabolism
      in sarcoidosis and how the pathophysiology affects management strategies.
      METHODS: : The literature concerning calcium metabolism in sarcoidosis was
      reviewed. RESULTS: : Dysregulated calcium metabolism is a well-recognized
      complication of sarcoidosis, resulting in hypercalcaemia (prevalence 5-10%),
      hypercalcuria (40-62%) and reduced bone density (40-55%). Extrarenal synthesis of
      calcitriol [1,25(OH)(2)D(3)] is central to the pathogenesis of abnormal calcium
      homeostasis, but alterations in parathyroid hormone (PTH) activity and the
      expression of PTH-related peptide have also been demonstrated. The
      immunosuppressive properties of calcitriol suggest that the raised levels seen in
      sarcoidosis could represent an adaptive response to the undefined antigen that
      causes sarcoidosis. CONCLUSIONS: : The mechanisms of abnormal calcium metabolism
      in sarcoidosis need to be understood when treating hypercalcaemia, hypercalcuria
      and corticosteroid-induced osteoporosis. Studies are required to determine if the
      currently available therapies for osteoporosis are safe and effective in
      sarcoidosis.

PMID- 10908688
TI  - A randomized controlled trial comparing topical piroxicam gel with a homeopathic
      gel in osteoarthritis of the knee.
AB  - OBJECTIVE: : To evaluate the efficacy and safety of a homeopathic gel vs an NSAID
      (piroxicam) gel in the treatment of osteoarthritis of the knee. METHOD: : One
      hundred and eighty-four out-patients with radiographically confirmed symptomatic
      osteoarthritis of the knee were entered into a pragmatic, randomized, double
      blind controlled trial and treated with 1 g of gel three times daily for 4 weeks.
      Main outcome measures were pain on walking as a Visual Analogue Score (VAS) and a
      single-joint Ritchie index. RESULTS: : One hundred and seventy-two of the 184
      enrolled patients had endpoints for the main outcome parameters. The pain
      reduction was 16.5 mm VAS in the homeopathy group (n = 86) and 8.1 mm in the
      piroxicam group (n = 86); the difference between treatment groups was 8.4 mm (95%
      confidence interval 0.8-15.9), and after adjustment for pain at baseline it was
      6.8 mm (95% confidence interval -0.3 to 13.8). There was no significant
      difference between treatment groups in the single-joint Ritchie index (P = 0.78).
      Adverse events occurred in 28 patients (12 homeopathy group, 5 withdrawn; 16
      piroxicam group, 9 withdrawn); 18 of the events involved a local reaction (7
      homeopathy group, 2 withdrawn; 11 piroxicam group, 5 withdrawn). CONCLUSION: :
      The homeopathic gel was at least as effective and as well tolerated as the NSAID
      gel. The presence of a clinically relevant difference between treatment groups
      cannot be excluded. The homeopathic gel supplemented by simple analgesics if
      required may provide a useful treatment option for patients with osteoarthritis.

PMID- 10908689
TI  - Validation of an Italian version of the arthritis impact measurement scales 2
      (ITALIAN-AIMS2) for patients with osteoarthritis of the knee. Gonarthrosis and
      Quality of Life Assessment (GOQOLA) Study Group.
AB  - OBJECTIVE: To validate a translated version of the revised and expanded Arthritis
      Impact Measurement Scales (AIMS2) to be used by Italian patients with
      osteoarthritis (OA) of the knee. METHODS: The AIMS2 was translated into Italian
      and administered to a cohort of 178 outpatients with symptomatic OA of the knee
      who attended 12 participating rheumatological institutes in northern, central and
      southern Italy. A random sample of 71 patients were readministered the AIMS2, 7
      days after the first visit, to evaluate the instrument's test-retest reliability.
      After 6 months, the subjects were asked to return to the institutes for a second
      administration of the questionnaire. RESULTS: The internal consistency
      reliability of each scale score, as estimated by Cronbach's alpha coefficient,
      was high and indicated that the components of the scale measured the same
      construct. The items all correlated with each other, but there was no redundancy;
      this indicates that each domain addressed a somewhat different aspect of
      functional disability. The test-retest reliability equalled or exceeded 0.80 for
      eight of the 12 scales. Factor analysis provided a three-factor health status
      model explaining 63.5% of the variance. Arthritis pain and psychological scale
      were loaded on the first factor, together with physical scales for mobility level
      and walking and bending. The upper limb function scales formed the second factor.
      The third factor was determined by the social dimension. These results
      demonstrate that the physical health status scales of the AIMS2 are valid, as
      shown by the significant, moderate to high correlations between the AIMS2
      subscales and the majority of the clinical measures. CONCLUSION: Our data suggest
      that, like the original questionnaire, the translated version of AIMS2 is a
      reliable, consistent and valid instrument for measuring health status and
      physical functioning in patients with OA of the knee.

PMID- 10908690
TI  - Interleukin-4 inhibits interleukin-11 production by rheumatoid synovial cells.
AB  - OBJECTIVE: To examine the effect of interleukin-4 (IL-4) on IL-11 production by
      rheumatoid synovial cells. METHODS: Freshly isolated rheumatoid synovial cells
      (FRS) were obtained by collagenase digestion of rheumatoid arthritis (RA)
      synovial tissue specimens taken at the time of operation. Rheumatoid synovial
      cells at four to eight passages were used as cultured rheumatoid synovial
      fibroblasts (RSF). IL-11 concentration was measured by ELISA. RESULTS: IL-4
      inhibited the production of IL-11 by FRS in a dose-dependent manner. This
      inhibition was observed in FRS obtained from six patients, and the mean
      inhibition was 46.5%. The inhibitory effect of IL-4 on IL-11 production was
      cancelled by the addition of anti-IL-4 antibody. IL-4 also inhibited IL-11
      production by IL-1alpha-stimulated cultured RSF. CONCLUSION: IL-4 inhibited IL-11
      production by rheumatoid synovial cells. IL-4 has a protective effect on bone
      resorption. On the contrary, IL-11 participates in bone resorption via
      osteoclastogenesis. Therefore, IL-4 may exert its protective effect on bone
      resorption, at least in part, via inhibition of IL-11 production in rheumatoid
      joints.

PMID- 10908691
TI  - The course of rheumatoid arthritis and predictors of psychological, physical and
      radiographic outcome after 5 years of follow-up.
AB  - OBJECTIVE: : To examine the course of RA over 5 yr and identify predictors of
      psychological, physical and radiographic outcome. PATIENTS AND METHODS: Out of
      238 patients with rheumatoid arthritis of no more than 4 (mean 2.2) yr duration,
      182 (76%) completed a clinical examination with follow-up at 1, 2, and 5 yr. The
      course of the disease was assessed by measures of psychological and physical
      health status, disease process and radiographic damage. RESULTS: : Over 5 yr we
      observed at a group level a stable disease course for measures of disease
      process, psychological and physical health status. Radiographic damage
      progressed. Health status and radiographic damage after 5 yr were predicted by
      the baseline measures for the respective outcome. Physical function was also
      predicted by age and by psychological status when the physical dimension of the
      Arthritis Impact Measurement Scales was chosen as outcome variable. Erythrocyte
      sedimentation rate and presence of rheumatoid factor predicted radiographic
      progression. CONCLUSIONS: : The 5 yr course of RA was characterized by preserved
      health status measures and clinically preserved disease process measures, whereas
      joint damage progressed steadily. Outcomes after 5 yr can be predicted partly by
      certain measures at baseline.

PMID- 10908692
TI  - Levels of markers of bone resorption are moderately increased in patients with
      inactive rheumatoid arthritis.
AB  - OBJECTIVE: Clinical remission occurs in 10-20% of patients with rheumatoid
      arthritis (RA). However, it is questionable whether clinical remission
      corresponds to the complete absence of the inflammatory process. To answer this
      question we measured collagen degradation products (which are known to be
      increased in active disease) in patients with inactive RA and in healthy
      controls. PATIENTS AND METHODS: The urinary levels of bone resorption markers
      (pyridinoline, deoxypyridinoline, N-terminal telopeptide and C-terminal
      telopeptide) were measured in 184 patients with inactive RA, as defined by the
      preliminary criteria of clinical remission of the American College of
      Rheumatology, and in 118 healthy individuals. RESULTS: After adjusting for age,
      concentrations of all four bone resorption markers were found to be significantly
      higher in patients with inactive RA than in healthy controls. CONCLUSION: The
      urinary excretion of bone resorption markers is increased in patients classified
      as having inactive RA. These results suggest that the inflammatory process is not
      completely absent.

PMID- 10908693
TI  - Prevalence of hip osteoarthritis and acetabular dysplasia in french and japanese
      adults.
AB  - OBJECTIVE: : To determine ethnic variations of acetabular morphology, and to
      delineate their relationship with hip osteoarthritis (OA). METHODS: : Radiographs
      of 283 French men, 118 French women, 414 Japanese men and 368 Japanese women,
      aged 20-79 yr, who underwent intravenous urography were assessed by a single
      observer for morphometric measurement and hip OA scoring. RESULTS: : The
      standardized morbidity ratio (SMR) for hip OA was highest in French men and
      lowest in Japanese men, whereas the SMR for acetabular dysplasia was highest in
      Japanese women and lowest in French men. French men and women had the highest
      centre-edge angle, followed by Japanese men then Japanese women. CONCLUSION: : In
      a large number of subjects assessed by a single observer, this study confirms
      other previous reports that the relationship between acetabular dysplasia and
      risk of hip OA is negative.

PMID- 10908694
TI  - Transcription factor decoy for NFkappaB inhibits cytokine and adhesion molecule
      expressions in synovial cells derived from rheumatoid arthritis.
AB  - OBJECTIVE: Numerous cytokines are expressed in lesions of synovial hyperplasia of
      patients with rheumatoid arthritis (RA), and their pathophysiological
      contributions have been the subject of speculation. These genes are regulated by
      the transcription factor NFkappaB which in turn is activated by tumour necrosis
      factor-alpha (TNF-alpha) and cytokines. In this study we examined the inhibition
      of the production of pro-inflammatory cytokines, adhesion molecule and matrix
      metalloproteinase (MMP) from synovial tissue of patients with RA by the
      introduction of synthetic double-stranded DNA with high affinity for the NFkappaB
      binding site. METHOD: NFkappaB decoy oligonucleotides (ODN) were introduced with
      the aid of the haemagglutinating virus of Japan (HVJ)-liposome method into
      synovial tissue or synovial cells derived from patients with RA. The levels of
      interleukin-1beta (IL-1beta), IL-6, TNF-alpha, intercellular adhesion molecule-1
      (ICAM-1) and MMP-1 were determined by means of enzyme-linked immunosorbent assay
      (ELISA) and Northern blotting analysis. A cell counting kit was used to study the
      effect of NFkappaB decoy ODN on synovial cell proliferation. RESULTS: The
      production of these mediators was significantly inhibited by the introduction of
      NFkappaB decoy ODN compared with the effect of scrambled decoy ODN. Transfection
      of NFkappaB decoy ODN resulted in a significant inhibition of synovial cell
      proliferation as compared with that of scrambled decoy ODN. CONCLUSION: The
      results demonstrated in this study suggest the potential usefulness of NFkappaB
      decoy ODN for gene therapy of inflammatory synovitis of RA.

PMID- 10908695
TI  - Major histocompatibility complex phenotypes influence serum testosterone
      concentration.
AB  - OBJECTIVES: (a) To confirm our earlier observation that the phenotype HLA-DR4,7
      occurs with higher frequency in male patients with rheumatoid arthritis (RA) than
      in female patients. (b) To test the hypothesis that DR7 is associated with low
      normal serum testosterone (Te) levels in healthy males; this might explain the
      increased frequency of DR4,7 in male patients since there appears to be a
      relationship between low serum Te and RA. (c) To characterize the association
      between HLA alleles and serum Te concentration in healthy males. METHODS: An
      additional 82 Newfoundland (NF) RA patients were HLA-DR typed and, combined with
      our earlier data and data from the 11th International Histocompatibility
      Workshop, gave HLA-DR and sex information on 373 RA patients. Ninety-four healthy
      NF males were typed for HLA, the microsatellite marker TNFa (located close to the
      tumour necrosis factor alpha gene) and complement factor B (BF). An additional 38
      males were included, selected partly based on their HLA-B type. RESULTS: We
      confirmed our earlier finding of a higher frequency of HLA-DR4,7 in male RA
      patients compared with female RA patients (P<0.01). Contrary to our expectations
      we found that DR7 was associated with higher than mean values of Te as were B5,
      B27, DR1, TNFa7 and BF F positivity. Conversely, low Te concentrations were found
      in men with B15, DR2, DR5, TNFa5 and who were BF F negative. In 28 male 'early
      onset' RA patients we did not find an increased frequency of HLA alleles
      associated with low Te levels as compared with the frequency in 41 'late-onset'
      patients, suggesting that if low Te level is a risk factor and is present before
      onset of RA then the level cannot be explained by an association between Te level
      and major histocompatibility complex (MHC) phenotype. CONCLUSION: This study
      indicates that a man's MHC phenotype may influence his serum Te concentration,
      but the relationship of this, if any, to the pathogenesis of RA remains an area
      of speculation.

PMID- 10908696
TI  - Onset and severity of inflammation in rats exposed to the learned helplessness
      paradigm.
AB  - OBJECTIVE: To test the hypothesis that there is an association between
      susceptibility to inflammation and a hyporesponsive hypothalamo-pituitary-adrenal
      (HPA) axis. METHODS: Animals were separated on the basis of behaviour in the
      learned helplessness (LH) paradigm into groups of LH(+) (i.e. animals which did
      not escape footshock) and LH(-) animals. Adjuvant-induced arthritis (AA) was
      subsequently induced in the LH(+) and LH(-) animals. RESULTS: Plasma
      corticosterone was significantly increased in response to the LH test in the LH(
      ) compared with the LH(+) rats. We observed an earlier onset and increased
      inflammation in the LH(-) rats in spite of the greater corticosterone response to
      the acute stress. We noted lower levels of plasma testosterone in the LH(-)
      animals suggesting a possible influence for this protective factor in AA.
      CONCLUSION: These data suggest that increased onset and severity of inflammation
      in AA is not a simple consequence of an attenuated HPA axis response to stress as
      proposed in the Lewis rat. Indeed we have observed the converse. Together these
      data suggest that the balance of pro- and anti-inflammatory factors released in
      response to stress may influence the progress of AA.

PMID- 10908697
TI  - Radiographic change is common in new presenters in primary care with hip pain.
      PCR Hip Study Group.
AB  - OBJECTIVE: To determine the prevalence of radiographic osteoarthritis in subjects
      with hip pain newly presenting to primary care. METHODS: The study was cross
      sectional in design, set in 35 general practices across the UK. It included 195
      men and women aged 40 yr and over (median 63 yr) presenting with a new episode of
      hip pain. Hip radiographs were scored for minimum joint space (MJS) and overall
      Croft's modification of the Kellgren and Lawrence (Croft)-grade of
      osteoarthritis. RESULTS: In all, definite evidence of radiographic change in the
      painful joint was common: Croft grade > or =2 in 44%, > or =3 in 34%. MJS of 2.5
      mm or less was seen in 30% of whom half were below 1.5 mm. There were no
      significant gender differences in radiographic severity. CONCLUSIONS:
      Radiographic change is common in patients newly presenting with hip pain and many
      already have advanced disease.

PMID- 10908698
TI  - Percutaneous image-guided biopsy of lung nodules in the assessment of disease
      activity in Wegener's granulomatosis.
AB  - OBJECTIVE: In patients with known Wegener's granulomatosis (WG) and persistent
      chest radiographic abnormalities, assessment for disease activity is often
      difficult, prompting the need for histological diagnosis to determine appropriate
      treatment. Here we report the use of automated image-guided core needle biopsy of
      pulmonary lesions for the assessment of disease activity in WG, rather than for
      primary diagnosis. METHODS: Image-guided percutaneous core needle biopsy was
      performed on five occasions in four patients with thoracic WG and persistent
      radiographic abnormalities of the chest. Clinical features, indication for
      biopsy, radiographic abnormalities and pathological findings were recorded.
      RESULTS: Adequate pathological specimens were obtained, allowing exclusion of
      infection and tumour. Active chronic inflammation with or without vasculitis was
      demonstrated in each case, indicating the need for further immunosuppressive
      therapy. A small pneumothorax following biopsy in one case required no treatment.
      Follow-up chest imaging revealed a reduction in the extent of thoracic disease
      following therapy in all cases. CONCLUSIONS: The safety and diagnostic accuracy
      of image-guided core biopsy of thoracic lesions makes it a useful tool in the
      assessment of disease activity in WG patients with persistent chest radiographic
      lesions.

PMID- 10908699
TI  - Use of health status measures in patients with low back pain in clinical
      settings. Comparison of specific, generic and preference-based instruments.
AB  - OBJECTIVE: To evaluate the discriminative performance over time of specific,
      generic and preference-based instruments in patients with low back pain (LBP) in
      clinical settings. METHODS: Forty-six consecutive patients with LBP participated
      in the study. Self-response questionnaires were administered at baseline and 3
      and 6 months, including the following instruments: Oswestry (specific for LBP),
      SF-36 (generic), EuroQol (EQ-5D) and Health Utilities Index (HUI) (preference
      based). EQ-5D and HUI weights were derived from previously published evaluations
      in the general population. Patients were asked to compare their health status
      with their baseline health and were categorized on the basis of an ordinal scale
      as: (a) improved; (b) stable; or (c) worse. Changes in the instruments were
      evaluated by rescaling the instruments over the same scale interval and by
      estimating standardized effect sizes between two time points for the three
      categories of change. RESULTS: Thirty-seven patients (80%) completed both the
      baseline and the 3-month questionnaire and 34 the baseline and 6-month
      questionnaires (74%). Overall, at both time points, approximately half of the
      patients reported no changes in their health status. Correlations between
      instruments were generally low, suggesting that they measure different health
      domains. The scales which discriminated best between patients who improved and
      those who deteriorated at 3 months were the Oswestry, the HUI, the EQ-5D and the
      SF-36 bodily pain and emotional role subscales. The SF-36 subscales appeared to
      have a floor effect for those patients who had deteriorated. CONCLUSIONS: Most SF
      36 subscales did not adequately reflect changes in the health status of patients
      with LBP, mostly for those who reported deterioration. Preference-derived quality
      of-life scores appeared to discriminate among patients who improved and those who
      deteriorated, although not as consistently as the disease-specific measure
      (Oswestry). Additional research is needed to evaluate the role of generic
      measures of quality of life in the assessment of patients with LBP before they
      can be widely implemented in clinical settings or outcomes research.

PMID- 10908700
TI  - Willingness to pay in arthritis: a Danish contribution.
AB  - OBJECTIVE: To explore the use of willingness-to-pay (WTP) methods with respect to
      an antagonist of tumour necrosis factor as an antirheumatic drug. METHODS: One
      hundred and fifteen rheumatoid arthritis (RA) patients at a tertiary care centre
      in Odense, Denmark were interviewed using two WTP approaches, the contingent
      ranking and double-bounded (closed-ended) methods. RESULTS: The average closed
      ended WTP value was DKr581 and the average contingent ranking WTP was DKr643.
      There were no statistically significant differences in the WTP estimates between
      the two methods. CONCLUSION: It is feasible to use these methods with arthritis
      patients. If, as suggested in a number of recent reviews, a major effort is to be
      put into undertaking economic appraisals of arthritis programmes, then this
      should include more cost-benefit studies using WTP approaches of the kind
      illustrated in this paper.

PMID- 10908701
TI  - Undergraduate rheumatology teaching in the UK: a survey of current practice and
      changes since 1990. Arthritis Research Campaign Undergraduate Working Party of
      the ARC Education Sub-committee.

PMID- 10908702
TI  - Plasma adrenomedullin level in systemic lupus erythematosus.

PMID- 10908703
TI  - Sjogren's syndrome co-existing with limited Wegener's granulomatosis.

PMID- 10908704
TI  - An unusual case of adult varicella-associated arthritis.

PMID- 10908705
TI  - Soluble adhesion molecules in rheumatoid arthritis.

PMID- 10908707
TI  - Regional rheumatology meetings. British Society for Rheumatology Research,
      Training Subcommittee.

PMID- 10908706
TI  - Etoposide in Wegener's granulomatosis.

PMID- 10908709
TI  - Re: polytopic spondylodiskitis secondary to streptococcus bovis endocarditis

PMID- 10908708
TI  - Daily folate supplementation is adequate prophylaxis against methotrexate-induced
      nausea and vomiting and avoids the need for expensive anti-emetic prescription.

PMID- 10908710
TI  - Robin goodfellow

PMID- 10908711
TI  - Correlates of linguistic rhythm in the speech signal.
AB  - Spoken languages have been classified by linguists according to their rhythmic
      properties, and psycholinguists have relied on this classification to account for
      infants' capacity to discriminate languages. Although researchers have measured
      many speech signal properties, they have failed to identify reliable acoustic
      characteristics for language classes. This paper presents instrumental
      measurements based on a consonant/vowel segmentation for eight languages. The
      measurements suggest that intuitive rhythm types reflect specific phonological
      properties, which in turn are signaled by the acoustic/phonetic properties of
      speech. The data support the notion of rhythm classes and also allow the
      simulation of infant language discrimination, consistent with the hypothesis that
      newborns rely on a coarse segmentation of speech. A hypothesis is proposed
      regarding the role of rhythm perception in language acquisition.

PMID- 10908712
TI  - Substrate binding and enzyme function investigated by infrared spectroscopy.
AB  - Protein conformational changes triggered by molecule binding are increasingly
      investigated by infrared spectroscopy often using caged compounds. Several
      examples of molecule-protein recognition studies are given, which focus on
      nucleotide binding to proteins. The investigation of enzyme mechanisms is
      illustrated in detail using the Ca(2+)-ATPase of the sarcoplasmic reticulum
      membrane as an example. It is shown that infrared spectroscopy provides valuable
      information on general aspects of enzyme function as well as on molecular details
      of molecule-protein interactions and the mechanism of catalysis.

PMID- 10908713
TI  - Binding of camphor to Pseudomonas putida cytochrome p450(cam): steady-state and
      picosecond time-resolved fluorescence studies.
AB  - The binding of camphor to cytochrome P450(cam) has been investigated by steady
      state and time-resolved tryptophan fluorescence spectroscopy to obtain
      information on the substrate access channel. The fluorescence quenching
      experiments show that some of the tryptophan residues undergo changes in their
      local environment on camphor binding. The time-resolved fluorescence decay
      profile gives four lifetime components in the range from 99 ps to 4.5 ns. The
      shortest lifetime component assigned to W42 lies close to the proposed camphor
      access channel. The results show that the fluorescence of W42 is greatly affected
      on binding of camphor, and supports dynamic fluctuations involved in the passage
      of camphor through the access channel as proposed earlier on the basis of
      crystallographic, molecular dynamics simulation and site-directed mutagenesis
      studies.

PMID- 10908714
TI  - A sequence in the carboxy-terminus of the alpha(1C) subunit important for
      targeting, conductance and open probability of L-type Ca(2+) channels.
AB  - The role of the 80-amino acid motif 1572-1651 in the C-terminal tail of alpha(1C)
      Ca(2+) channel subunits was studied by comparing properties of the conventional
      alpha(1C,77) channel expressed in HEK-tsA201 cells to three isoforms carrying
      alterations in this motif. Replacement of amino acids 1572-1651 in alpha(1C,77)
      with 81 non-identical residues leading to alpha(1C,86) impaired membrane
      targeting and cluster formation of the channel. Similar to alpha(1C, 86),
      substitution of its 1572-1598 (alpha(1C,77L)) or 1595-1652 (alpha(1C,77K))
      segments into the alpha(1C,77) channel yielded single-channel Ba(2+) currents
      with increased inactivation, reduced open probability and unitary conductance,
      when compared to the alpha(1C,77) channel. Thus, the C-terminal sequence 1572
      1651 of the alpha(1C) subunit is important for membrane targeting, permeation and
      open probability of L-type Ca(2+) channels.

PMID- 10908715
TI  - Characterization of dehydrodolichyl diphosphate synthase of Arabidopsis thaliana,
      a key enzyme in dolichol biosynthesis.
AB  - The enzyme dehydrodolichyl diphosphate (dedol-PP) synthase is a cis
      prenyltransferase that catalyzes the synthesis of dedol-PP, the long-chain
      polyprenyl diphosphate used as a precursor for the synthesis of dolichyl
      phosphate. Here we report the cloning and characterization of a cDNA from
      Arabidopsis thaliana encoding dedol-PP synthase. The identity of the cloned
      enzyme was confirmed by functional complementation of a yeast mutant strain
      defective in dedol-PP synthase activity together with the detection of high
      levels of dedol-PP synthase activity in the transformed yeast mutant. The A.
      thaliana dedol-PP synthase mRNA was detected at high levels in roots but was
      hardly detected in flowers, leaves, stems and in A. thaliana suspension-cultured
      cells.

PMID- 10908716
TI  - Anoxia pretreatment protects soybean cells against H(2)O(2)-induced cell death:
      possible involvement of peroxidases and of alternative oxidase.
AB  - Anoxia followed by reoxygenation causes extensive damage to cellular components
      through generation of reactive oxygen intermediates. We examined cellular
      responses to oxidative stress after anoxia in cultured soybean or human
      fibroblast cells. Anoxia pretreatment protected soybean but not fibroblasts
      against H(2)O(2) concentrations that induced programmed cell death in normoxic
      cells. H(2)O(2) removal in anoxia-pretreated soybean cultures was faster.
      Protection was associated with increased action of alternative oxidase (AOX) and
      peroxidases. AOX inhibitors abolished the protective effect, while induction of
      AOX protected normoxic cells against H(2)O(2). We propose that during anoxia,
      plant cells can prepare for reoxygenation injury by up-regulating their
      antioxidant capacity, and that AOX is involved in this process.

PMID- 10908717
TI  - Xanthophylls of the major photosynthetic light-harvesting complex of plants:
      identification, conformation and dynamics.
AB  - The electronic transitions of lutein and neoxanthin in the major light-harvesting
      complex, LHCIIb, have been identified for the first time. It was found that 0-0,
      0-1 and 0-2 transitions of neoxanthin were located around 486, 457 and 430 nm,
      whilst those for lutein were dependent on the oligomerisation state. For the
      monomer, the absorption bands of lutein were found at 495, 466 and 437 nm.
      Trimerisation caused a decrease in lutein absorption and the parallel appearance
      of an additional absorption band around 510 nm, which was identified by resonance
      Raman excitation spectra to originate from lutein. Circular dichroism
      measurements together with analysis of the nu(4) resonance Raman region of
      xanthophylls suggested that this lutein molecule is distorted in the trimer. This
      feature is not predicted by the LHCIIb atomic model of Kuhlbrandt and co-workers
      [Kuhlbrandt, W., Wang, D.N. and Fugiyoshi, Y. (1994) Nature 367, 614-621] and is
      an important step in understanding pigment dynamics of the complex.
      Oligomerisation of trimers led to a specific distortion of the neoxanthin
      molecule. These observations suggest that the xanthophylls of LHCIIb sense the
      protein conformation and which may reflect their special role in the assembly and
      function of the light-harvesting antenna of higher plants.

PMID- 10908718
TI  - The galactose-binding and mannose-binding jacalin-related lectins are located in
      different sub-cellular compartments.
AB  - A galactose-specific and a mannose-specific lectin of the family of the jacalin
      related lectins have been localized by immunofluorescence microscopy. The present
      localization studies provide for the first time unambiguous evidence for the
      cytoplasmic location of the mannose-specific jacalin-related lectin from rhizomes
      of Calystegia sepium, which definitely differs from the vacuolar location of the
      galactose-specific jacalin from Artocarpus integrifolia. These observations
      support the hypothesis that the galactose-specific jacalin-related lectins
      evolved from their mannose-specific homologues through the acquisition of
      vacuolar targeting sequences.

PMID- 10908719
TI  - A viable ubiquitin-activating enzyme mutant for evaluating ubiquitin system
      function in Saccharomyces cerevisiae.
AB  - Ligation of proteins to ubiquitin requires activation of ubiquitin by E1, the
      ubiquitin-activating enzyme. Mutant alleles of E1 in mammalian cells have been
      crucial for dissecting the contribution of the ubiquitin system to cell function.
      Comparable mutants have been unavailable for Saccharomyces cerevisiae. Here we
      describe the isolation and characterization of a hypomorphic allele of S.
      cerevisiae E1. Protein modification by ubiquitin is strongly impaired in the
      mutant, inhibiting degradation of ubiquitin-proteasome pathway substrates as well
      as ubiquitin-dependent but proteasome-independent degradation of membrane
      receptors. This allele will be a useful tool for evaluating the ubiquitin
      dependence of cellular processes in yeast, even those in which the proteasome is
      not involved.

PMID- 10908720
TI  - Interaction of viper venom serine peptidases with thrombin receptors on human
      platelets.
AB  - The serine peptidases, thrombocytin and PA-BJ, isolated from the venom of
      Bothrops atrox and Bothrops jararaca, respectively, induce platelet aggregation
      and granule secretion without clotting fibrinogen. The specific platelet
      aggregation activity of each enzyme was about 15 times lower than that of
      thrombin. This activity was blocked by monoclonal antibodies recognizing protease
      activated receptor 1 (PAR1) and by heparin, but not by hirudin nor
      thrombomodulin. Both enzymes induced calcium mobilization in platelets and
      desensitized platelets to the action of thrombin and the SFLLRN peptide. We
      compared the effect of thrombin, PA-BJ, and thrombocytin on the degradation of
      the soluble N-terminal domain of the PAR1 receptor. The major cleavage site by
      thrombin and both viper enzymes was Arg41-Ser42. In addition, a rapid cleavage of
      the peptide bond at Arg46-Asn47 by the viper enzymes was observed, resulting in
      the inactivation of the tethered ligand. PA-BJ and thrombocytin both cleaved at
      41-42 and 46-47 peptide bonds, and fragment 42-103 disappeared rapidly. Both
      viper enzymes caused calcium mobilization in fibroblasts transfected with PAR4
      and desensitized these cells to the thrombin action. In conclusion, both PAR1 and
      PAR4 mediate the effect of viper venom serine peptidases on platelets.

PMID- 10908721
TI  - A synapomorphic disulfide bond is critical for the conformational stability and
      cytotoxicity of an amphibian ribonuclease.
AB  - Onconase((R)) (ONC) is a homolog of ribonuclease A (RNase A) that has unusually
      high conformational stability and is toxic to human cancer cells in vitro and in
      vivo. ONC and its amphibian homologs have a C-terminal disulfide bond, which is
      absent in RNase A. Replacing this cystine with a pair of alanine residues greatly
      decreases the conformational stability of ONC. In addition, the C87A/C104A
      variant is 10-fold less toxic to human leukemia cells. These data indicate that
      the synapomorphic disulfide bond of ONC is an important determinant of its
      cytotoxicity.

PMID- 10908722
TI  - Activated protein C suppresses tissue factor expression on U937 cells in the
      endothelial protein C receptor-dependent manner.
AB  - The new functional role of activated protein C (APC) in the regulation of tissue
      factor (TF) expression was investigated using the cultured human monoblastic
      leukemia U937 cell line. A flow cytofluorometric analysis demonstrated that
      treatment with APC resulted in time- and dose-dependent decrease in TF expression
      in unstimulated and phorbol ester-stimulated cells. The effect was antagonized by
      the monoclonal antibody (mAb) to endothelial protein C/APC receptor (EPCR), 252,
      which strongly inhibited the interaction between APC and EPCR. In contrast, mAbs
      49 and 379, which bind to EPCR without blocking APC binding, had no or only a
      modest effect. It is concluded that culturing U937 cells in the presence of APC
      caused down-regulation of TF expression through the EPCR-dependent mechanism,
      independent of whether induction was triggered by phorbol ester.

PMID- 10908723
TI  - Use of an activation-specific probe to show that Rap1A and Rap1B display
      different sensitivities to activation by forskolin in rat1 cells.
AB  - Rap1A and Rap1B are small GTPases of the Ras superfamily whose activation can be
      measured using a probe that interacts specifically with the GTP-bound forms of
      Rap1A and Rap1B. Using this procedure we demonstrate that the cyclic AMP
      elevating agent forskolin activates both Rap1A and Rap1B in Rat1 cells. Whilst
      the protein kinase A inhibitor H89 ablated the ability of forskolin to cause cAMP
      response element binding protein (CREB) phosphorylation in Rat1 cells, it did not
      affect the ability of forskolin to activate either Rap1A and Rap1B. Forskolin
      differentially activated Rap1A and Rap1B isoforms in a time- and dose-dependent
      manner. The cAMP-specific type 4 family phosphodiesterase inhibitor rolipram
      potentiated the rate of activation of both Rap1A and Rap1B by forskolin challenge
      of Rat1 cells. Challenge of Rat1 cells with rolipram alone was able to elicit the
      phosphorylation of CREB but not activation of either Rap1A or Rap1B.

PMID- 10908724
TI  - Trichodion, a new inhibitor of inflammatory signal transduction pathways from a
      Trichosporiella species.
AB  - In a search for new inhibitors of the IFN-gamma mediated signal transduction in
      HeLa S3 cells using secreted alkaline phosphatase (SEAP) as reporter gene, the
      novel pyran-dione trichodion was isolated from fermentations of the imperfect
      fungus Trichosporiella sp. 20-95. The compound inhibits the IFN-gamma mediated
      expression of the reporter gene with IC(50) values of 21-42 microM (5-10
      microgram/ml). The NF-kappaB and AP-1 mediated expression of the reporter gene
      are inhibited with IC(50) values of 42-84 microM (10-20 microgram/ml) and 21
      microM (5 microgram/ml) respectively. Western blotting with COX-2 and NOS II
      antibodies showed that the expression of both proinflammatory enzymes is almost
      completely inhibited at 21-42 microM (5-10 microgram/ml) in LPS/IFN-gamma
      stimulated J774 mouse macrophages. Studies on the mode of action of the compound
      revealed that the inhibition of the NF-kappaB dependent pathway is due to the
      stabilization of the IkappaB protein and the inhibition of the IFN-gamma
      dependent signaling is caused by an inhibition of the phosphorylation of the
      STAT1alpha transcription factor.

PMID- 10908726
TI  - Differential requirements for caspase-8 activity in the mechanism of
      phosphorylation of eIF2alpha, cleavage of eIF4GI and signaling events associated
      with the inhibition of protein synthesis in apoptotic Jurkat T cells.
AB  - Previously we have reported that induction of apoptosis in Jurkat cells results
      in an inhibition of overall protein synthesis with the selective and rapid
      cleavage of eukaryotic initiation factor (eIF) 4GI. For the cleavage of eIF4GI,
      caspase-3 activity is both necessary and sufficient in vivo, in a process which
      does not require signaling through the p38 MAP kinase pathway. We now show that
      activation of the Fas/CD95 receptor promotes an early, transient increase in the
      level of eIF2alpha phosphorylation, which is temporally correlated with the onset
      of the inhibition of translation. This is associated with a modest increase in
      the autophosphorylation of the protein kinase activated by double-stranded RNA.
      Using a Jurkat cell line that is deficient in caspase-8 and resistant to anti-Fas
      induced apoptosis, we show that whilst the cleavage of eIF4GI is caspase-8
      dependent, the enhancement of eIF2alpha phosphorylation does not require caspase
      8 activity and occurs prior to the cleavage of eIF4GI. In addition, activation of
      the Fas/CD95 receptor results in the caspase-8-dependent dephosphorylation and
      degradation of p70(S6K), the enhanced binding of 4E-BP1 to eIF4E, and, at later
      times, the cleavage of eIF2alpha. These data suggest that apoptosis impinges upon
      the activity of several polypeptides which are central to the regulation of
      protein synthesis and that multiple signaling pathways are involved in vivo.

PMID- 10908725
TI  - The HslU ATPase acts as a molecular chaperone in prevention of aggregation of
      SulA, an inhibitor of cell division in Escherichia coli.
AB  - HslVU is an ATP-dependent protease consisting of two multimeric components: the
      HslU ATPase and the HslV peptidase. SulA, which is an inhibitor of cell division
      and has high tendency of aggregation, is degraded by HslVU protease. Here we show
      that HslU plays a role not only as a regulatory component for the HslV-mediated
      proteolysis but also as a molecular chaperone. Purified HslU prevented
      aggregation of SulA in a concentration-dependent fashion. This chaperone activity
      required oligomerization of HslU subunits, which could be achieved by ATP-binding
      or in the presence of high HslU protein concentrations. hsl mutation reduced the
      SulA-mediated inhibition of cell growth and this effect could be reversed upon
      overproduction of HslU, suggesting that HslU promotes the ability of SulA to
      block cell growth through its chaperone function. Thus, HslU appears to have two
      antagonistic functions: one as a chaperone for promotion of the ability of SulA
      in cell growth inhibition by preventing SulA aggregation and the other as the
      regulatory component for elimination of SulA by supporting the HslV-mediated
      degradation.

PMID- 10908727
TI  - Two genes encoding distinct cytosolic glutamine synthetases are closely linked in
      the pine genome.
AB  - The major isoenzyme of glutamine synthetase found in leaves of angiosperms is the
      chloroplastic form. However, pine seedlings contain two cytosolic glutamine
      synthetases in green cotyledons: GS1a, the predominant isoform, and GS1b, a minor
      enzyme whose relative amount is increased following phosphinotricin treatment. We
      have cloned a GS1b cDNA, and comparison with the previously reported GS1a cDNA
      sequence indicated that they correspond to separate cytosolic GS genes encoding
      distinct protein products. Phylogenetic analysis showed that the newly reported
      sequence is closer to cytosolic angiosperm GS than to GS1a, suggesting therefore
      that GS1a could be a divergent gymnospermous GS1 gene. Gene mapping using a F2
      family of maritime pine showed co-localization of both GS genes on group 2 of the
      genetic linkage map. This result supports the proposed origin of different
      members of the GS1 family by adjacent gene duplication. The implications for
      gymnosperm genome organization are discussed.

PMID- 10908728
TI  - Annexin-I inhibits PMA-induced c-fos SRE activation by suppressing cytosolic
      phospholipase A2 signal.
AB  - Annexin-I (ANX-I) is a 37-kDa protein with a calcium-dependent phospholipid
      binding property. Previously we have observed the inhibition of cytosolic
      phospholipase A2 (cPLA2) by ANX-I in the studies using purified recombinant ANX
      I, and proposed a specific interaction model for the mechanism of cPLA2
      inhibition by ANX-I [Kim et al. (1994) FEBS Lett. 343, 251-255]. Here we have
      studied the role of ANX-I in the cPLA2 signaling pathway by transient
      transfection assay. The stimulation of Rat2 fibroblast cells with phorbol 12
      myristate 13-acetate (PMA) induced the c-fos serum response element (SRE). The
      SRE stimulation by PMA was dramatically reduced by (1) pretreatment with a cPLA2
      specific inhibitor, arachidonyltrifluoromethyl ketone, or (2) co-transfection
      with antisense cPLA2 oligonucleotide, indicating that the SRE activation was
      through cPLA2 activation. Co-transfection with an ANX-I expression vector also
      reduced the SRE stimulation by PMA, suggesting the inhibition of cPLA2 by ANX-I.
      The active domain of ANX-I was mapped using various deletion mutants. ANX-I(1
      113) and ANX-I(34-346) were fully active, whereas ANX-I(114-346) abolished the
      activity. Therefore the activity was in the amino acid 34 to 113 region, which
      corresponds to the conserved domain I of ANX-I.

PMID- 10908729
TI  - New role of glycosaminoglycans on the plasma membrane proposed by their
      interaction with phosphatidylcholine.
AB  - Glycosaminoglycan side chains of membrane proteoglycans have been claimed to be
      located at the outermost layer of the glycocalyx surrounding the cell. In this
      study measurements by surface plasmon resonance and solid-phase assay have shown
      that both chondroitin sulfate and keratan sulfate but not heparin associate with
      phosphatidylcholine under physiological conditions. Spectrophotometric
      measurements also showed that chondroitin sulfate restricts the lateral diffusion
      of phosphatidylcholine in liposomes. These findings indicate that chondroitin
      sulfate and/or keratan sulfate chains of membrane proteoglycans crouch on the
      surface of the membrane while heparan sulfate chains stretch outward from the
      membrane surface as postulated traditionally.

PMID- 10908730
TI  - Persistent increase in the amount of aquaporin-5 in the apical plasma membrane of
      rat parotid acinar cells induced by a muscarinic agonist SNI-2011.
AB  - SNI-2011 induces the long-lasting increase in the amount of aquaporin-5 (AQP5) in
      apical plasma membranes (APMs) of rat parotid acini in a concentration-dependent
      manner. This induction was inhibited by p-F-HHSiD, U73122, TMB-8, or dantrolene
      but not by bisindolmaleimide or H-7, indicating that SNI-2011 acting at M(3)
      muscarinic receptors induced translocation of AQP5 via [Ca(2+)](i) elevation but
      not via the activation of protein kinase C. In contrast, acetylcholine induced a
      transient translocation of AQP5 to APMs. SNI-2011 induces long-lasting
      oscillations of [Ca(2+)](i) in the presence of extracellular Ca(2+). Thus, SNI
      2011 induces a long-lasting translocation of AQP5 to APMs coupled with persistent
      [Ca(2+)](i) oscillations.

PMID- 10908731
TI  - Phosphorylation of the endothelial nitric oxide synthase at ser-1177 is required
      for VEGF-induced endothelial cell migration.
AB  - Vascular endothelial growth factor (VEGF) stimulates endothelial cell (EC)
      migration. The protein kinase Akt activates the endothelial NO synthase (eNOS) by
      phosphorylation of Ser-1177. Therefore, we investigated the contribution of Akt
      mediated eNOS phosphorylation to VEGF-induced EC migration. Inhibition of NO
      synthase or overexpression of a dominant negative Akt abrogated VEGF-induced cell
      migration. In contrast, overexpression of constitutively active Akt was
      sufficient to induce cell migration. Moreover, transfection of an Akt site
      phospho-mimetic eNOS (S1177D) potently stimulated EC migration, whereas a non
      phosphorylatable mutant (S1177A) inhibited VEGF-induced EC migration. Our data
      indicate that eNOS activation via phosphorylation of Ser-1177 by Akt is necessary
      and sufficient for VEGF-mediated EC migration.

PMID- 10908732
TI  - A direct photo-activated affinity modification of tetracycline transcription
      repressor protein TetR(D) with tetracycline(1).
AB  - Results of a first successful application of a direct photo-induced affinity
      modification of Tet repressor (TetR(D)) protein with tetracycline within a
      complex of known three-dimensional structure are described. The conditions of the
      modification have provided suitable yields of the modified complex and allowed
      characterization of the modified segments of the protein. The potential of
      tetracycline as a fine modifying reagent was established. In the complex of
      TetR(D) protein with tetracycline, the antibiotic modifies at least two segments,
      Ile59-Glu73 and Ala173-Glu183, which form a binding tunnel for the drug according
      to the X-ray analysis. These data open possibilities for the use of different
      tetracycline targets for structural studies in solution.

PMID- 10908733
TI  - Small proline-rich protein 1 is the major component of the cell envelope of
      normal human oral keratinocytes.
AB  - Oral keratinocytes of buccal and gingival tissues undergo a terminal
      differentiation program to form a protective epithelial barrier as non
      keratinized or parakeratinized stratified cells. We have examined the protein
      composition of cell envelopes (CEs) from normal human buccal and gingival tissues
      as well as keratinocytes from normal human gingival cells grown in culture.
      Biochemical and sequencing analyses reveal that the CEs contain 60-70% small
      proline-rich protein 1a/b (SPR1a/b), together with smaller amounts of involucrin,
      annexin I and several other known CE proteins. The data imply a specialized role
      for SPR1 proteins in the unique barrier function requirements of oral epithelia.

PMID- 10908734
TI  - kappa-Opioid inhibits catecholamine biosynthesis in PC12 rat pheochromocytoma
      cell.
AB  - It was reported that nicotine-induced dopamine release in the rat
      pheochromocytoma cell line, PC12 cells, was inhibited by kappa-opioid. However,
      it is not known whether inhibition of catecholamine biosynthesis is involved in
      the inhibitory mechanisms of kappa-opioids in PC12 cells. U-69593 (a kappa-opioid
      agonist: >/=100 nM) significantly inhibited the nicotine-induced increase of
      tyrosine hydroxylase (TH, a rate-limiting enzyme in biosynthesis of
      catecholamine) enzyme activity and TH mRNA levels. These inhibitory effects were
      completely reversed by naloxone and nor-binaltorphimine dihydrochloride (nor
      BNI), a specific kappa-antagonist, whereas pertussis toxin (PTX) only partially
      reversed this inhibitory effect. Also, U-69593 (>/=100 nM) significantly
      inhibited the nicotine-induced increase of cAMP production. This inhibitory
      effect was completely reversed by naloxone and nor-BNI, whilst only partially
      reversed by PTX. Moreover, U-69593 (>/=100 nM) significantly inhibited the
      nicotine-induced increase of both the TH protein level and intracellular
      catecholamine levels. These results indicate that the anti-cholinergic actions of
      kappa-opioid can be explained partially by its inhibition of both TH enzyme
      activity and TH synthesis, through suppression of the cAMP/protein kinase A
      pathway. It would also appear that the PTX-sensitive G-protein mediates the
      inhibitory effect of this pathway, at least in part.

PMID- 10908735
TI  - ATPase cycle controls the conformation of an archaeal chaperonin as visualized by
      cryo-electron microscopy.
AB  - Chaperonins are double-ring protein folding machines fueled by ATP binding and
      hydrolysis. Conformational rearrangements upon ATPase cycling of the group I
      chaperonins, typified by the Escherichia coli GroEL/GroES system, have been
      thoroughly investigated by cryo-electron microscopy and X-ray crystallography.
      For archaeal group II chaperonins, however, these methods have so far failed to
      provide a correlation between the structural and the functional states. Here, we
      show that the conformation of the native alphabeta-thermosome of Thermoplasma
      acidophilum in vitrified ice is strictly regulated by adenine nucleotides.

PMID- 10908737
TI  - Corrigendum to: identification of a hydrogen bond in the phe-M197-->Tyr mutant
      reaction center of the photosynthetic purple bacterium rhodobacter sphaeroides by
      X-ray crystallography and FTIR spectroscopy (FEBS 23044).

PMID- 10908736
TI  - Comments on identification of a hydrogen bond in the phe-M197-->Tyr mutant
      reaction center of the photosynthetic purple bacterium Rhodobacter sphaeroides by
      x-ray crystallography and FTIR spectroscopy (FEBS 23044).

PMID- 10908738
TI  - Corrigendum to: kinetic and spectroscopic characterization of native and metal
      substituted beta-lactamase from aeromonas hydrophila AE036 (FEBS 23250).

PMID- 10908740
TI  - Percutaneous intramedullary fixation of trochanteric fractures of the femur.
      Clinical trial of a new hip nail.
AB  - Since 1992, we have developed an implant which can be inserted percutaneously
      without reaming the femoral shaft. In the final design, the intramedullary nail
      is 13 mm diameter proximally and 11 mm distally. The femoral head is fixed with
      two screws of 6.5 mm diameter, and there is a single 4.5 mm distal screw. The
      nail and screws are constructed from coldworked ISO 5832-9 stainless steel. From
      July 1994 to June 1997, 159 patients aged over 60 years with acute trochanteric
      femoral fractures were treated with these implants. Results were assessed on a
      functional basis of walking mobility and level of dependency. After three months,
      89 patients (56%) had regained their previous level of mobility and 22 patients
      (16%) had died from unrelated causes. Average operating time for the first 50
      patients was 38 min. Complications include screw cutout in two patients,
      prominent screws in four, one non-union and two persistent low grade infections.
      The complication rate is comparable with that of other methods of treatment.

PMID- 10908739
TI  - Experience with over 2500 diagnostic peritoneal lavages.
AB  - This study was undertaken to confirm the safety and efficacy of diagnostic
      peritoneal lavage (DPL) for trauma patients. A prospectively maintained database
      of all DPLs performed in the past 75 months was analyzed. A red blood cell count
      of 100,000/mm(3) was considered positive for injury in blunt trauma; 10,000/mm(3)
      was considered positive for peritoneal penetration in penetrating trauma.
      Information relative to type of injury, DPL result, laparotomy result and
      complications, was analysed to determine if DPL was more or less suited to any
      specific indication or type of patient. Over a 75 month period, 2501 DPLs were
      performed at our urban level I trauma center. The overall sensitivity,
      specificity and accuracy for the above thresholds were 95, 99 and 98%. The
      majority (2409, 96%) were performed using percutaneous or "closed" seldinger
      technique. Ninety-two (4%) were performed using open technique because of pelvic
      fractures, previous scars and pregnancy. Open DPL was less sensitive than closed
      DPL in patients who sustained blunt trauma (90 vs 95%) but slightly more
      sensitive in determining penetration (100 vs 96%). Overall, there were 21
      complications (0.8%). There was no difference in complication rate between open
      and closed DPL. In conclusion, DPL remains a highly accurate, sensitive and
      specific test with an extremely low complication rate. It can be performed either
      open or closed with comparable results. We recommend its use in the evaluation of
      both blunt and penetrating trauma.

PMID- 10908741
TI  - Tendo Achillis rupture; surgical repair is a safe option.
AB  - We reviewed the results of 67 tendo Achillis repairs performed at one District
      General Hospital over a 5-year period, using details from a comprehensive
      database. At a mean follow-up of 2.5 years, the re-rupture rate was 3% (2 out of
      67). The infection rate was 1.5% (1 out of 67). A review of the relevant
      literature has revealed that quoted infection rates following tendo Achillis
      repair vary considerably, and are as high as 21%. Several authors have advised
      against repair based on those data. In the light of our results, we can recommend
      surgical repair of tendo Achillis rupture as a safe option.

PMID- 10908742
TI  - A comparison of patient characteristics and survival in two trauma centres
      located in different countries.
AB  - INTRODUCTION: The aim of the study was to compare patient characteristics and
      mortality in severely injured patients in two trauma centres located in different
      countries, allowing for differences in case-mix. It represents a direct bench
      marking exercise between the trauma centres at the North Staffordshire Hospital
      (NSH), Stoke-on-Trent, UK and the Oregon Health Sciences University (OHSU)
      Hospital, Portland, Oregon, USA. METHODS: Patients of all ages admitted to the
      two hospitals during 1995 and 1996 with an Injury Severity Score >15 were
      included, except for those who died in the emergency departments. Twenty-three
      factors were studied, including the Injury Severity Score, Glasgow Coma Score,
      mechanism of injury and anatomical site of injury. Outcome analysis was based on
      mortality at discharge. RESULTS: The pattern of trauma differed significantly
      between Stoke and Portland. Patients from Stoke tended to be older, presented
      with a lower conscious level and a lower systolic blood pressure and were
      intubated less frequently before arriving at hospital. Mortality depended on
      similar factors in both centres, especially age, highest AIS score, systolic
      blood pressure and Glasgow Coma Score.The crude analysis of mortality showed a
      highly significant odds-ratio of 1.64 in Stoke compared with Portland. Single
      factor adjustments were made for the above four factors, which had a similar
      influence on mortality in both centres. Adjusting for the first three factors
      individually did not alter the odds-ratio, which stayed in the range 1.53-1.59
      and remained highly significant. Adjusting for the Glasgow Coma Score reduced the
      odds-ratio to 0.82 and rendered it non-significant. In a multi-factor logistic
      regression model incorporating all of the factors shown to influence mortality in
      either centre, the odds-ratio was 1.7 but was not significant. CONCLUSION: The
      analysis illustrates the limitations and pitfalls of making crude outcome
      comparisons between centres. Highly significant differences in crude mortality
      were rendered non-significant by case-mix adjustments, supporting the null
      hypothesis that the two centres were equally effective in terms of this short
      term indicator of outcome. To achieve a meaningful comparison between centres,
      adjustments must be made for the factors which affect mortality.

PMID- 10908743
TI  - A five year study of high falls in Edinburgh.
AB  - High falls are a common cause of death and disability. The aim of this study was
      to obtain an epidemiologically complete picture of all high falls over a 5 year
      period in Edinburgh, Scotland. Prospectively collected data on hospital survivors
      and hospital deaths was collected from the Scottish Trauma Audit Group (STAG)
      database. Data on prehospital deaths was obtained from autopsy reports and
      detailed police enquiry reports. There were 341 patients in the study, of whom
      82% were male. Seventy-four percent survived to hospital discharge. Sixty-three
      percent of the total deaths appeared to be suicides. Head and chest injuries were
      responsible for the majority of deaths. Pelvis, limb and vertebral injuries
      predominated in survivors. In conclusion, prevention may be the most effective
      method of reducing prehospital deaths. Abdominal injuries were associated with a
      poor outcome, but survival might improve with immediate surgical exploration in
      haemodynamically unstable patients.

PMID- 10908744
TI  - The Ilizarov method in infected nonunion of fractures.
AB  - Thirty patients with infected non-union of long bones were treated with radical
      resection of the necrotic bone and bone transport or compression/distraction
      osteosynthesis. Non-union, infection, deformity, bone gap and shortening were all
      addressed simultaneously using the Ilizarov principles. There were 15 cases with
      bone loss ranging from 4 to 12 cm (median bone gap of 7 cm), 10 cases of stiff
      non-union (six of which had an associated deformity) and five cases of mobile non
      union. The median time in the Ilizarov frame was 150 days. Median follow up time
      after frame removal was 23.5 months. Bone grafting at the docking site was only
      required in three cases (10%). There were three cases of refracture (10%) and
      three cases of recurrence of infection (10%). The bone result was excellent in 21
      patients (70%), good in three (10%), fair in none (0%) and poor in six (20%). The
      functional results were excellent in eight patients (26.7%), good in 12 (40.0%),
      fair in three (10%) and poor in seven (23.3%). It is difficult to precisely
      define the indications for preservation and reconstruction of severe injuries.
      The surgical team has to take into account the length, disability, complications
      and cost of treatment. Patients must be aware of the limitations of functional
      results and the possible difficulty of return to work despite the reconstructive
      attempt.

PMID- 10908745
TI  - The management of elderly blunt trauma victims in Scotland: evidence of ageism?
AB  - Health services are challenged with providing trauma care to an increasingly
      elderly population. The objectives of this study were to determine the in
      hospital mortality for injured elderly patients, and by analysing key features of
      their management, to ascertain whether these trauma patients were managed less
      aggressively than their younger counterparts. Main outcome measures included; use
      of resuscitation room facilities, senior medical staff involvement, admission to
      intensive care units, transfers to regional neurosurgical centres and mortality.
      Three thousand seven hundred patients initially managed in a resuscitation room
      were significantly younger (mean age 43) than those not treated in this area
      (mean age 54, 95% CI 10.7-12.4). Considering seriously injured patients with a
      significant head injury (who did not present in coma) those transferred to
      neurosurgical care were younger (mean age 44) than patients who were not
      transferred (mean age 49, 95% CI 1. 6-8.6). Logistic regression analysis showed
      that age did not have a significant independent effect on the seniority of
      medical response from key specialties. For the severely injured, the odds of
      being admitted to an intensive care unit when aged 70 in comparison to age 30
      were 0.7436 (95% CI 0.5787-0.9559). Overall in-hospital mortality of the 290
      elderly patients who had sustained major trauma was 42.1%. Significantly more of
      the elderly died than would be predicted. Age appears to be an independent factor
      in the process of trauma care in Scottish hospitals. We consider that outcomes
      for the injured elderly could be improved by a more dynamic approach to their
      management.

PMID- 10908746
TI  - Strain development in carpal scaphoid for various wrist positions: a cadaveric
      study using strain gauges.
AB  - In order to investigate the ideal position in which the wrist should be
      immobilized during scaphoid fracture, treatment the strains which are developed
      in the carpal scaphoid for various wrist positions has been recorded in cadaveric
      wrists, using strain gauges. The data obtained shows that during radial deviation
      with neutral or slight palmar flexion of the wrist the waist of the scaphoid
      tends to compress because of the development of strong compressive strains, while
      the strain development parallel to the fracture site that tends to shift the
      scaphoid waist is minimum. This position seems to be the best for stable scaphoid
      fracture immobilization.

PMID- 10908747
TI  - Mortality following surgery for proximal femoral fractures in centenarians.
AB  - Although the number of centenarians in our population is increasing, mortality
      rates following hip fracture in this group of patients has not yet been reported.
      The medical records of a consecutive series of 13 centenarians with proximal
      femoral fractures who presented to the Derbyshire Royal Infirmary over a 20 year
      period were retrospectively reviewed. The majority of patients were female (M:F
      2:11) and had suffered intertrochanteric fractures. The recorded incidence of
      surgical complications was low. The mortality at 30 days, 6 months and 1 year
      were 31%, 50% and 56%, respectively representing a 20% increase in mortality at 1
      year when compared to the expected mortality rates among their non-injured peers.
      When compared with over 1000 hip fracture patients of all ages in previous
      prospective studies, the centenarians in this series were found to have a
      significantly higher mortality during hospital admission (p<0.001) and at 1 year
      (p=0.002). The treatment of hip fractures in centenarians poses a challenge.
      Optimal anaesthesia, expeditious surgery and a co-ordinated multidisciplinary
      approach to care is essential in these patients.

PMID- 10908748
TI  - Fracture blisters and sodium valproate: two case reports.

PMID- 10908749
TI  - Superior dislocation of the patella--a rare but important differential diagnosis
      of acute knee pain--a case report and review of the literature.

PMID- 10908751
TI  - Traumatic tension chylothorax.

PMID- 10908750
TI  - Triplane fracture of the proximal tibia.

PMID- 10908752
TI  - Incarcerated, strangulated handlebar hernia.

PMID- 10908753
TI  - Late neurological symptoms after internal fixation of a pelvic fracture due to
      breakage of an iliosacral screw.

PMID- 10908754
TI  - A new technique for treatment of a non-union of a lateral humeral condyle.

PMID- 10908755
TI  - Fetal weight prediction by thigh volume measurement with three-dimensional
      ultrasonography.
AB  - OBJECTIVE: To evaluate the usefulness and accuracy of a simple method of
      predicting fetal weight by measuring fetal thigh volume with three-dimensional
      ultrasonography. METHODS: In 84 pregnant women, fetuses without structural or
      chromosomal anomalies were studied prospectively and cross-sectionally.
      Biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL)
      were measured by two-dimensional ultrasound. Fetal thigh volume was measured by
      three-dimensional ultrasound, using three cross-sectional images of femur, from
      proximal, middle, and distal parts of femur diaphysis. Infants were delivered
      within 48 hours after ultrasound examinations. RESULTS: Modified thigh volume
      measurements using three cross-sectional images of femur by three-dimensional
      ultrasound were correlated strongly with birth weight (R(2) = 0.921, P <.001).
      Using linear and polynomial regression, we calculated a new best-fit formula:
      Birth weight (g) = 165.32 + 28.78 x modified thigh volume (mL). The mean and
      standard deviation of the residual were 121.8 and 110.4, respectively, in three
      dimensional formulas, which were significantly smaller than those of two
      dimensional formulas. CONCLUSION: Thigh volume measurement using three cross
      sectional images of femur by three-dimensional ultrasound was simple, and there
      was better accuracy with this method than with two-dimensional ultrasound methods
      for predicting fetal weight during the third trimester of pregnancy.

PMID- 10908756
TI  - Absent umbilical artery end-diastolic velocity in growth-restricted fetuses: a
      risk factor for neonatal thrombocytopenia.
AB  - OBJECTIVE: To examine the relationship between umbilical artery (UA) end
      diastolic flow and neonatal thrombocytopenia. METHODS: We prospectively examined
      115 anatomically normal single fetuses with UA pulsatility indices more than two
      standard deviations above the gestational age mean and subsequent birth weights
      below the tenth percentile. Peripheral neonatal platelet counts in fetuses with
      positive UA end-diastolic velocity were compared with those of fetuses with
      absent or reversed UA end-diastolic velocity. RESULTS: Sixty-seven fetuses
      (58.3%) had positive UA end-diastolic velocity and 48 (41.7%) had absent or
      reversed UA end-diastolic velocity. Three neonates in the positive-flow group and
      22 neonates in the absent- or reversed-flow group had platelet counts of less
      than 100, 000/mm(3) (relative risk 10.2; 95% confidence interval; 3.2, 32.3; P
      <.001). Absent or reversed end-diastolic velocity had a sensitivity of 88%,
      specificity of 71%, positive predictive value of 46%, and negative predictive
      value of 96% for predicting neonatal thrombocytopenia. Neonates with absent or
      reversed flow also had lower median platelet counts (101,500/mm(3) versus
      208,000/mm(3), P <.001), hemoglobin levels (15.1 versus 16.4 g/dL, P <.01), and
      hematocrits (47.6 versus 51.1%, P <.05), as well as higher nucleated red blood
      cell counts (191 versus 15 per 100 white blood cells, P <. 001). CONCLUSION:
      Absent or reversed UA end-diastolic velocity in growth-restricted fetuses is
      associated with a statistically significant increase in risk of neonatal
      thrombocytopenia.

PMID- 10908757
TI  - Internal jugular vein blood flow in normal and growth-restricted fetuses.
AB  - OBJECTIVE: To assess internal jugular vein blood flow patterns during the second
      half of pregnancy in normal and growth-restricted fetuses. METHODS: We did
      Doppler ultrasound studies of internal jugular veins and the inferior vena cavas
      longitudinally on 21 normal singleton fetuses from 20 weeks to term, and on eight
      growth-restricted fetuses with absent end-diastolic flow at the umbilical artery
      (UA). The three components of the venous flow velocity waveforms were used to
      calculate peak velocity ratio: Peak systolic velocity (S wave) minus reverse peak
      velocity (R wave) divided by peak velocity during early diastole (D wave) and
      velocity time integral ratio: systolic velocity time integral minus reverse
      velocity time integral divided by velocity time integral during early diastole.
      Statistical analysis of longitudinal measurements used K-related samples Friedman
      test; groups were compared with Mann-Whitney U test and chi(2) test. RESULTS: In
      normal fetuses we found significant increases in peak velocity ratio and velocity
      time integral ratio of internal jugular veins and the inferior vena cavas
      throughout gestation. The mean +/- standard deviation (SD) of the internal
      jugular veins peak velocity ratio (1.12 +/- 0.4 versus 1.46 +/- 0.15, P <.05) and
      velocity time integral ratio (1.1 +/- 0.2 versus 1.55 +/- 0.17, P <.05) were
      significantly lower in growth-restricted fetuses compared with normal fetuses at
      28-32 weeks' gestation but inferior vena cava indices were not. None of the eight
      growth-restricted fetuses had umbilical venous pulsations or changes in inferior
      vena cava or ductus venosus blood flow patterns. All had arterial pH above 7.15
      at birth. CONCLUSION: Growth-restricted fetuses with absent end-diastolic
      velocity in the UA have changes in internal jugular vein blood flow patterns that
      probably indicate increased cerebral blood flow, more evidence of redistribution
      of blood flow in growth-restricted fetuses that can be used to maintain them.

PMID- 10908758
TI  - Outcome of very low birth weight infants with histopathologic chorioamnionitis.
AB  - OBJECTIVE: To determine neonatal outcome at 7 months of corrected age in very low
      birth weight (VLBW) infants with placental chorioamnionitis. METHODS: We
      conducted a cohort study of 287 VLBW infants delivered as a result of preterm
      premature rupture of membranes (PROM) or preterm labor. Control subjects (n =
      123) had placentas with absent umbilical cord inflammation and absent or low
      grade membrane inflammation. Case subjects (n = 164) had moderate membrane
      inflammation or any umbilical cord inflammation. Neonatal and 7-month outcomes
      were compared. A power analysis showed that 98 total subjects were needed to
      reject the two-sided null hypothesis with a difference in mean Bayley index
      scores of at least 8. RESULTS: Infants in the study group had significantly more
      preterm PROM, antenatal antibiotics, lower birth weight, lower gestational age,
      longer duration of ruptured membranes, and clinical chorioamnionitis.
      Intraventricular hemorrhage occurred more commonly in infants with placentas
      demonstrating chorioamnionitis (relative risk = 1.6, 95% confidence interval 1.1,
      2.4, P =.013). One hundred sixty-seven (69%) of the 243 surviving infants had 7
      month follow-up. There was no difference between cases and controls in mean
      Bayley mental developmental index (93 compared with 90, P =.25), psychomotor
      developmental index (89 compared with 90, P =.68), or in the number of infants
      that were developmentally delayed. CONCLUSION: Despite a higher frequency of
      intraventricular hemorrhage, no difference in developmental scores was detected
      at 7 months of corrected age in VLBW infants with histologic chorioamnionitis.

PMID- 10908759
TI  - Perinatal death and tocolytic magnesium sulfate.
AB  - OBJECTIVE: To determine whether there is a significant association between
      perinatal mortality and exposure to total doses of tocolytic magnesium sulfate
      larger than 48 g. METHODS: We did a case-control study in which cases were
      defined as neonates or fetuses who died after being exposed to tocolytic
      magnesium sulfate and controls were those who survived exposure. The study
      included fetuses and neonates who weighed between 700 and 1249 g and whose
      mothers had received tocolytic magnesium sulfate at Chicago Lying-in Hospital
      between January 1, 1986, and March 31, 1999. We excluded women who received
      prophylactic magnesium sulfate for preeclampsia or preeclampsia superimposed on
      chronic hypertension, and fetuses or neonates with major congenital anomalies.
      Data were analyzed by Fisher exact test, chi(2) test, Student t test, Mann
      Whitney U test, multivariable logistic regression, and Cochrane-Armitage trend
      test. RESULTS: Controlling for birth weight or gestational age, year of delivery,
      receipt of betamethasone, acute maternal disease, and maternal race in a
      multivariable model, we found that exposure to total doses of tocolytic magnesium
      sulfate exceeding 48 g was significantly associated with increased perinatal
      mortality (adjusted odds ratio 4. 7; 95% confidence interval 1.1, 20.0; P =.035).
      Using the Cochrane-Armitage trend test, we found that a significant dose response
      was present (P =.03), but one that was most consistent with a threshold effect.
      CONCLUSION: Our findings support the hypothesis that high doses of tocolytic
      magnesium sulfate are associated with increased perinatal mortality among fetuses
      and neonates weighing 700-1249 g.

PMID- 10908760
TI  - Infant mortality and early postpartum discharge.
AB  - OBJECTIVE: To assess additional risk of newborn death owing to early discharge.
      METHODS: This was a historical cohort study using Washington State linked birth
      certificates, death certificates, and hospital discharge records that covered
      47,879 live births in 1989 and 1990. Logistic regression was used to assess risk
      of death within the first year of life after early discharge (less than 30 hours
      after birth) compared with later discharge (30-78 hours after birth). RESULTS:
      Newborns discharged early were more likely to die within 28 days of birth (odds
      ratio [OR] 3.65; 95% confidence interval [CI] 1.56, 8.54), between 29 days and 1
      year (OR 1.61; 95% CI 1.10, 2.36), and any time within the first year (OR 1.84;
      95% CI, 1.31, 2.60) of life than newborns sent home later. Newborns discharged
      early also were more likely to die of heart-related problems (OR 3.72; CI 1.25,
      11.04) and infections (OR 4.72; CI 1.13, 19.67) within 1 year of birth than
      newborns discharged later. CONCLUSION: Newborns discharged within 30 hours of
      birth are at increased risk of death within the first year of life.

PMID- 10908761
TI  - Bone loss in adolescent and adult pregnant women.
AB  - OBJECTIVE: To determine the amount of change in bone ultrasound measures among
      pregnant adolescent girls and women and whether that change was associated with
      adolescence, maternal growth during pregnancy, limited weight gain during
      pregnancy, hypertension in pregnancy, or poor diet. METHODS: We used bone
      ultrasound measurements of attenuation and sound velocity to assess changes in
      quantitative ultrasound indices of 252 pregnant adolescent girls and women age 12
      34 years. Bone ultrasound measurement of the os calcis was performed at 16 +/- 7
      weeks' gestation (mean +/- standard deviation and 6 +/- 1 weeks postpartum.
      RESULTS: On average, the bone quantitative ultrasound index was 3.6% lower 6
      weeks postpartum than at entry into care (P <.001). Nulliparous patients had
      significantly greater bone loss than did parous subjects. Still-growing
      adolescents had greater quantitative ultrasound index decreases than did grown
      women (-5.5% versus -1.9%, P <.02). Patients in the upper tertile of baseline
      quantitative ultrasound index lost more bone than did patients in the lower
      tertile (-5% versus 0.5%, P <.02). Pregravid weight, weight change during
      pregnancy, gynecologic age, and age at menarche predicted bone change in
      subgroups defined by parity or age; however, none of the differences in those
      variables were statistically significant. Greater dietary calcium intake, less
      physical activity, and pregnancy hypertension and preeclampsia were not
      associated with bone change. CONCLUSION: There has been inconsistent evidence of
      maternal bone loss during pregnancy. The findings of this study challenge the
      assumption that because of increased calcium absorption from the maternal
      intestine, no transitory bone loss occurs in pregnancy. The amount of bone loss
      among growing adolescents and nulliparous patients was consistent with the
      demands of fetal mineralization and the continued demands of the maternal
      skeleton during growth.

PMID- 10908762
TI  - Prepregnancy body mass index and pregnancy weight gain: associations with preterm
      delivery. The NMIHS Collaborative Study Group.
AB  - OBJECTIVE: To examine associations between rate of pregnancy weight gain and
      preterm delivery among women of varying prepregnancy body mass indices (BMI).
      METHODS: Subjects were 3511 mother-infant pairs from the 1988 National Maternal
      and Infant Health Survey. Prenatal weight measured between 14 and 28 weeks'
      gestation was used to calculate rate of pregnancy weight gain for each woman.
      Weight gain (lb/week) was categorized as low (under 0.5), average (0.5-1.5), or
      high (above 1.5). Prepregnancy BMI was calculated as weight divided by height in
      (kg/m(2)) and categorized as low (under 19.8), average (19.8-26.0), and high
      (above 26). Delivery before 37 weeks' gestation was considered preterm.
      Associations between BMI, weight gain, and preterm delivery were examined before
      and after exclusion of medically indicated preterm deliveries and pregnancies
      complicated by maternal medical conditions potentially related to weight gain or
      fetal growth restriction. Associations were expressed as odds ratios (OR)
      adjusted for several potential confounding factors. RESULTS: Women with low
      pregnancy weight gain were at increased risk of preterm delivery. The magnitude
      of risk varied according to a woman's prepregnancy BMI. After all exclusions and
      adjustments for confounders, ORs, and 95% confidence intervals (CI) for low
      pregnancy weight gain were 6.7 (1.1, 40.6) for underweight women, 3.6 (1.6, 8.0)
      for average-weight women, and 1.6 (0.7, 3.5) for overweight women compared with
      average-weight women with average pregnancy weight gain. CONCLUSIONS: Low weight
      gain in pregnancy was associated with increased risk of preterm delivery,
      particularly if women were underweight or of average weight before pregnancy.

PMID- 10908763
TI  - Biophysical profile in predicting acute ascending infection in preterm rupture of
      membranes before 32 weeks.
AB  - OBJECTIVE: To assess the performance of the biophysical profile (BPP) and its
      components within 24 hours of delivery in predicting histopathologic evidence of
      severe acute placental inflammation in women with premature rupture of membranes
      (PROM) before 32 weeks' gestation. METHODS: We examined placentas from a series
      of consecutive, nonanomalous, live-born, singleton infants delivered before 32
      weeks' gestation after PROM. In 166 cases, biophysical profiles (BPP) were done
      within 24 hours of birth. Histologic evidence of acute inflammation was assessed
      in the maternal (amnion) and fetal (chorionic and umbilical cord vessels)
      compartments, and scored on a severity scale of 0-4 by a single pathologist
      masked to clinical data. The presence and severity of acute inflammation was
      related to BPP results and its individual components. RESULTS: The overall
      prevalence of severe acute inflammation, ie, a score of 3 or 4, was 59% (98 of
      166). In 30 (18%) cases it was present in the amnion, in 49 (30%) cases in
      chorionic or umbilical cord vessels, and in 19 (11%) cases in maternal and fetal
      compartments. There was no association between abnormal BPP score and presence or
      absence of severe acute placental inflammation (48% versus 46%, P =.7). Our study
      had a 90% power to detect a 0.26 difference between them. When rates of abnormal
      BPP scores were compared in cases with different degrees of acute inflammation in
      the maternal, fetal, or both compartments, no association was found. When the
      individual components of the BPP were analyzed in relation to site and severity
      of acute inflammation, no association was detected. CONCLUSION: We did not find
      evidence of a dose-response relationship between acute placental inflammation and
      BPP score or its individual components in cases of PROM with infants delivered
      before 32 weeks. Mediators other than infection might affect BPP in preterm PROM.

PMID- 10908764
TI  - First-trimester Down syndrome screening using dried blood biochemistry and nuchal
      translucency.
AB  - OBJECTIVE: To assess the effectiveness of free beta-hCG, pregnancy-associated
      plasma protein A, and nuchal translucency in a prospective first-trimester
      prenatal screening study for Down syndrome and trisomy 18. METHODS: Risks were
      calculated for Down syndrome and trisomy 18 based on maternal age and
      biochemistry only (n = 10,251), nuchal translucency only (n = 5809), and the
      combination of nuchal translucency and biochemistry (n = 5809). RESULTS: The
      study population included 50 Down syndrome and 20 trisomy 18 cases. Nuchal
      translucency measurement was done on 33 Down syndrome and 13 trisomy 18 cases.
      Down syndrome screening using combined biochemistry and ultrasound resulted in a
      false-positive rate of 4.5% (95% confidence interval [CI] 3.9%, 5.2%) and
      detection rate of 87.5% (95% CI 47%, 100%) in patients under age 35 years. In
      older patients, the false-positive rate was 14.3% (95% CI 12.7%, 15. 8%) and
      detection rate was 92% (95% CI 74%, 99%). For trisomy 18 screening, the false
      positive rate was 0.4% (95% CI 0.24%, 0.69%) and detection rate was 100% (95% CI
      40%, 100%) in younger patients, whereas in older patients the false-positive rate
      was 1.4% (95% CI 0. 9%, 2.0%) and detection rate was 100% (95% CI 66%, 100%).
      Using modeling, at a fixed 5% false-positive rate, the Down syndrome detection
      rate was 91%. Conversely, at a fixed 70% Down syndrome detection rate, the false
      positive rate was 1.4%. CONCLUSION: First-trimester screening for Down syndrome
      and trisomy 18 is effective and offers substantial benefits to clinicians and
      patients.

PMID- 10908765
TI  - Predictors of episiotomy use at first spontaneous vaginal delivery.
AB  - OBJECTIVE: To identify factors associated with the use of episiotomy at
      spontaneous vaginal delivery. METHODS: We studied 1576 consecutive term,
      singleton, spontaneous vaginal deliveries in nulliparas at Brigham & Women's
      Hospital between December 1, 1994 and July 31, 1995. The association of
      demographic variables and obstetric factors with the rate of episiotomy use were
      examined. Adjusted odds ratios (OR) and confidence intervals (CI) were estimated
      from multiple logistic regression analysis. RESULTS: The overall rate of
      episiotomy was 40.6% (640 of 1576). Midwives performed episiotomies at a lower
      rate (21.4%) than faculty (33.3%) and private providers (55.6%) (P =. 001). After
      controlling for confounding factors with logistic regression, private practice
      provider was the strongest predictor of episiotomy use (OR, 4.1; 95% CI, 3.1,
      5.4) followed by faculty provider (OR, 1.7; 95% CI, 1.1, 2.5), prolonged second
      stage of labor (OR, 1.8; 95% CI, 1.2, 2.7), fetal macrosomia (OR, 1.6; 95% CI,
      1.1, 2.5), and epidural analgesia (OR 1.4, 95% CI, 1.1, 1.8). CONCLUSION: The
      strongest factor associated with episiotomy at delivery was the category of
      obstetric provider. Obstetric and demographic factors evaluated did not readily
      explain this association.

PMID- 10908767
TI  - Endoglin expression as a measure of microvessel density in cervical cancer.
AB  - OBJECTIVE: To evaluate endoglin, a membrane protein and member of the
      transforming growth factor beta-1 receptor complex, as an endothelial marker of
      angiogenesis in cervical cancer tissues. METHODS: Tumor tissue was collected from
      31 surgically treated stage IB nonbulky (under 5 cm) cervical cancer subjects,
      and samples were fixed in formalin and embedded in paraffin. Endoglin was stained
      on 5-microm slide sections by the DAKO Catalyzed Signal Amplification method
      (DAKO Corporation, Carpinteria, CA). Factor VIII was stained by standard
      immunohistochemistry. Positively stained microvessels were counted in "hot spots"
      at 200x magnification. Clinical data were correlated with vessel counts by
      Spearman correlation. Mean differences in counts were tested using paired t
      tests. RESULTS: This staining method for endoglin identified significantly more
      vessels than the factor VIII method (mean 92 +/- 45 versus 33 +/- 16, P <. 001).
      Endoglin and factor VIII counts correlated significantly with deep stromal
      invasion (Spearman rho 0.466 and 0.522, respectively, P <.05); however, only
      endoglin counts correlated significantly with lymph node metastases (rho =.495, P
      <.01). CONCLUSION: Endoglin is stimulated in tumor angiogenesis and might be
      relatively more specific than commonly used endothelial markers. The endoglin
      system was more sensitive for staining capillaries in neoplastic cervical tissue,
      better predicted lymph node metastases, and should be widely applicable for the
      study of other tumors.

PMID- 10908766
TI  - Frequency of cervical smear abnormalities within 3 years of normal cytology.
AB  - OBJECTIVE: To compare cervical screening outcomes associated with age and three
      screening intervals, 1, 2, and 3 years. METHODS: We did a prospective cohort
      study comprising 128,805 women at community-based clinics throughout the United
      States who were screened for cervical cancer within 3 years of normal smears
      through the National Breast and Cervical Cancer Early Detection Program. We
      determined the incidence of cytologic abnormalities defined as atypical squamous
      cells of undetermined significance (ASCUS), low-grade squamous intraepithelial
      lesion (SIL), high-grade SIL, and suggestive of squamous cell cancer. RESULTS:
      Over the 3 years after normal smear results, the incidence of new smears
      interpreted as high-grade SIL or suggestive of squamous cell cancer (high-grade
      SIL or worse) was 66 of 10,000 for women under 30 years old, 22 of 10, 000 for
      those 30-49 years, 15 of 10,000 for those 50-64 years, and 10 of 10,000 for those
      over 65 years. Age-adjusted incidence rates of high-grade SIL or worse were
      similar for women screened at 9-12 months (25 of 10,000), 13-24 months (29 of
      10,000), and 25-36 months (33 of 10,000) after normal smears (P =.46). Age
      adjusted incidence rates of ASCUS, the most common cytologic abnormality, did not
      change (P =.36). Incidence of smears interpreted as low-grade SIL increased as
      time from the normal smear increased (P =.01). CONCLUSIONS: Within 3 years after
      normal cytology results, cervical smears interpreted as high-grade SIL or worse
      are uncommon, and the incidence rate is unrelated to the time since last normal
      smear. Optimal screening strategies for women with recent normal cytology results
      should be based on comprehensive modeling studies that incorporate the true risks
      and benefits of repetitive screening.

PMID- 10908768
TI  - Noninflammatory ovarian masses in girls and young women.
AB  - OBJECTIVE: We reviewed the presentation, treatment, and pathologic diagnoses of
      girls and young women less than 21 years old with noninflammatory ovarian masses
      that required surgery and established whether treatment had changed over time.
      METHODS: We retrospectively reviewed charts of all girls and young women under 21
      years old with International Classification of Diseases, 9th Revision (ICD-9)
      codes specific for noninflammatory ovarian masses treated at our institution from
      June 1980 to July 1998 (n = 140). RESULTS: The median age at surgery was 15 years
      (range 2 days-21 years). Ovarian cysts occurred in 57.9% (81 of 140) of patients,
      benign tumors (including mature cystic teratomas) in 30% (42 of 140), malignant
      tumors in 7.9% (11 of 104), and torsed but normal ovaries in 4.3% (six of 140) of
      the study sample. Patients older than 15 years were more likely to have ovarian
      cysts and benign tumors than younger patients (P =.019). There were no
      malignancies among girls with neonatal cysts. The incidence of ovarian torsion
      was 17.8% (25 of 140). Patients with ovarian cysts, mature cystic teratomas, and
      normal ovaries were more likely to have torsion than those with other benign or
      malignant tumors (P <.001). Operative approach and surgical procedure were
      compared before and after July 1, 1989. Laparoscopy was performed more commonly
      after July 1, 1989 (P =.009). However, patient age (P <.001) rather than time of
      surgery (P =.83) was the most important predictive factor in a multivariate
      analysis for use of laparoscopy. In addition, multivariate analysis revealed that
      patient age (P =.02) rather than time of surgery (P =.79) was also predictive of
      surgeon type (gynecologist or pediatric surgeon). CONCLUSION: The most frequent
      cause of an ovarian mass requiring surgery in a girl or young woman under 21
      years of age is an ovarian cyst, which justifies consideration of a laparoscopic
      approach. Patient age rather than time of surgery predicted operative approach
      and surgeon type. Caution should be exercised in patients over age 12 months with
      a complex mass on ultrasound and clinical evidence of hormonal activity, as these
      masses are usually malignant.

PMID- 10908769
TI  - Suprapubic bladder drainage after extraperitoneal cystotomy.
AB  - OBJECTIVE: To observe the effects of cessation of continuous bladder drainage
      after short-term catheterization in women who had extraperitoneal cystotomies.
      METHODS: The study population included 84 women, 78 of whom had retropubic
      urethropexies and six of whom had retropubic paravaginal repairs. Intentional
      cystotomy was done intraoperatively to assure ureteral patency, bladder
      integrity, and no inadvertent suture penetration into the bladder. All
      cystotomies were closed in two layers with 3-0 chromic suture. Suprapubic
      catheters were placed intraoperatively in all cases. In all women except four
      with gross hematuria, continuous bladder drainage was stopped and voiding trials
      were started within 24 hours after surgery. Suprapubic catheters were removed
      when women spontaneously voided 80% of total bladder volume. RESULTS: Suprapubic
      catheters were discontinued on average 4.1 days after surgery (range 2.7-14.1
      days). Average bladder volume at initial clamping of the suprapubic catheter was
      382 mL (range 224-510 mL). At this volume the integrity of the cystotomy should
      have been challenged appropriately. The women were observed for a minimum of 3
      months with no immediate or long-term complications. CONCLUSION: Extraperitoneal
      cystotomy in a nondependent portion of the bladder does not require continuous
      bladder drainage for more than 24 hours. This information should allow pelvic
      surgeons to be more liberal with intraoperative cystotomies if bladder integrity
      or ureteral patency needs to be confirmed.

PMID- 10908770
TI  - Rizatriptan in the treatment of menstrual migraine.
AB  - OBJECTIVE: To determine the efficacy of oral rizatriptan 10 mg and 5 mg for
      treating menstrually associated migraine attacks. METHODS: Data from two large
      clinical trials with identical designs were included in a retrospective analysis.
      The studies were randomized, double-masked, placebo-controlled, incomplete block,
      two-period, crossover designs. Women with migraines were randomly assigned to one
      of five treatment sequences for the treatment of two migraine attacks. Only data
      from the first attack in women with migraines who were treated with rizatriptan
      or placebo were included in the analysis. A menstrually associated attack was
      defined as one that occurred within 3 days before or after the onset of the last
      menstrual period. RESULTS: In the subgroup of 335 women with menstrually
      associated migraine, rizatriptan was effective compared with placebo. At 2 hours
      after dosing, 68% of 139 women taking rizatriptan 10 mg and 70% of 115 women
      taking rizatriptan 5 mg with a menstrually associated migraine had pain relief
      compared with 44% of 81 patients taking placebo (P <.05). In all women,
      rizatriptan was as effective in treating menstrual as well as nonmenstrual
      migraine: 68% of 139 patients taking rizatriptan 10 mg with a menstrually
      associated migraine had pain relief at 2 hours after dosing compared with 69% of
      393 patients with nonmenstrually associated attacks (test of menstrual
      association = nonsignificant; the analysis had 80% power to detect a difference
      of six percentage points between groups). Similar results were found for
      rizatriptan 5 mg (menstrual = 70%, nonmenstrual = 66%; not statistically
      significant). CONCLUSION: Rizatriptan is effective in the treatment of
      menstrually associated migraine attacks.

PMID- 10908771
TI  - Prolonged endocrine responses to medroxyprogesterone in postmenopausal women with
      respiratory insufficiency.
AB  - OBJECTIVE: To evaluate the endocrinologic changes associated with, and possibly
      responsible for, prolonged ventilatory improvement after short-term
      medroxyprogesterone acetate (MPA) in chronic respiratory failure. METHODS:
      Fourteen postmenopausal women with permanent or previous episodic hypercapnic or
      hypoxemic respiratory failure were enrolled in a placebo-controlled, 12-week,
      single-mask trial including 14-day treatment periods with placebo and MPA (60 mg
      daily) and a 6-week follow-up. We evaluated the duration of MPA-induced
      alterations on serum concentrations of progesterone, estradiol, testosterone,
      FSH, LH, sex hormone-binding globulin (SHBG), and prolactin. Hormones were
      measured four times: at baseline, after 14 days with MPA, and during the washout
      on days 21 and 42. RESULTS: With MPA, FSH decreased 42.7% (P <.001, 95%
      confidence interval [CI] -54.2, -31.6), LH 62.1% (P <.01; 95% CI -81. 0, -32.6),
      and SHBG 58.1% (P <.001; 95% CI -63.0, -43.9). Luteinizing hormone remained
      decreased (-28.7%; P <.01; 95% CI -42.0, -14.2) at the 3-week washout, whereas
      FSH and SHBG were back to pretreatment levels. Prolactin had a borderline initial
      increase of 23.5% (P =.097; 95% CI -3.5, 50.5) with MPA and a significant
      increase at the 3-week (31.9%; P <.05; 95% CI 1.0, 62.9) and 6-week (26.4%; P
      <.05; 95% CI 4.4, 48.3) washouts. CONCLUSION: Medroxyprogesterone acetate 60 mg
      daily for 2 weeks has both immediate (FSH, LH, and SHBG), prolonged (LH), and
      rebound endocrinologic (prolactin) effects up to 6 weeks after treatment. The MPA
      induced widespread endocrine aftereffects could explain the earlier reported
      prolonged ventilatory improvement.

PMID- 10908772
TI  - Low-dose contraceptive estrogen-progestin and coronary artery atherosclerosis of
      monkeys.
AB  - OBJECTIVE: To determine the separate and combined effects of the estrogen and
      progestin components of a modern triphasic oral contraceptive (OC) formulation on
      extent of coronary artery atherosclerosis. METHODS: Female cynomolgus monkeys (n
      = 81) were fed atherogenic diets for 32 months. After the first 7 months, they
      were randomized to four groups and treated triphasically for 21 of each 28 days
      with ethinyl estradiol (E2) (monkey equivalent of 30-40 microg), levonorgestrel
      (monkey equivalent of 50-125 microg), a combination of the two steroids, or
      placebo. RESULTS: Treatment with estrogen alone reduced coronary artery
      atherosclerosis extent 67% compared with untreated controls (P <.05). Treatment
      with progestin alone had no effect (P >.20). While atherosclerosis extent in
      monkeys treated with the combined OC was reduced 28%, this did not differ
      statistically from the other groups (P >.20). CONCLUSION: In doses used for oral
      contraception, E2, like all other estrogens studied to date, has a marked
      inhibitory effect on atherosclerosis progression. Levonorgestrel, at doses used
      in modern OC formulations, antagonizes this effect. When considered with other
      experimental evidence, these findings support the concept that progestins used in
      OCs and hormone replacement therapy can antagonize estrogen's atheroinhibitory
      effects. Whether this occurs seems to depend on a relative balance between
      estrogen and progestin with respect to dose, potency, route, and pattern of
      administration. However, when considered with evidence from previous studies, the
      findings also indicate a modest atheroinhibitory influence of combination
      (estrogen-progestin) OCs.

PMID- 10908773
TI  - Vaginal clindamycin and oral metronidazole for bacterial vaginosis: a randomized
      trial.
AB  - OBJECTIVE: To compare the efficacy and safety of clindamycin vaginal ovules with
      oral metronidazole for treatment of bacterial vaginosis. METHODS: Women with
      bacterial vaginosis received either 100-mg ovules of clindamycin (intravaginally
      for 3 consecutive days) plus placebo capsules (orally twice daily for 7 days) or
      metronidazole 500 mg (two 250-mg capsules orally twice daily for 7 days) plus
      placebo ovules (intravaginally for 3 consecutive days). The sample was determined
      prospectively to provide a probability of.84 of correctly concluding that the
      rate of success for clindamycin is not more than 15% less than the expected 75%
      success rate for metronidazole. Clinical outcome was determined on the basis of
      vaginal fluid amine odor and clue cells. RESULTS: Of the 399 patients enrolled,
      233 could be evaluated for efficacy. Of those, 77 (68.1%) of 113 patients were
      cured with clindamycin, compared with 80 (66. 7%) of 120 who were cured with
      metronidazole (95% confidence interval -10.6%, 13.4%; P =.810). Treatment-related
      adverse events were reported more frequently in the metronidazole treatment
      group. Systemic symptoms, such as nausea and taste perversion, accounted for most
      of the difference between groups. CONCLUSION: A 3-day regimen of clindamycin,
      given as intravaginal ovules, was as effective as and better tolerated than a 7
      day regimen of oral metronidazole 500 mg, given twice daily, for treatment of
      bacterial vaginosis.

PMID- 10908774
TI  - Nicotine replacement prescription practices of obstetric and pediatric
      clinicians.
AB  - OBJECTIVE: To assess smoking cessation counseling and nicotine replacement
      therapy prescription and recommendation practices among obstetric and pediatric
      providers. METHODS: We sent out a self-administered survey to 61 obstetric and
      pediatric nurse practitioners and physicians at six community health centers in
      the Boston area. RESULTS: Obstetric providers were more likely to view smoking
      cessation counseling as their responsibility in treating pregnant women than
      pediatric providers did in treating infants with mothers who smoked (mean +/-
      standard deviation [95% confidence interval] 4.5 +/- 0.76 [4.2, 4.8] versus 4.0
      +/- 0.8 [3.7, 4.3] on a five-point scale; P <.05). Obstetric providers believed
      that smoking cessation counseling was more effective than did pediatric providers
      (3.45 +/- 1.1 [3.0, 3.9] versus 2.8 +/- 0.8 [2.5, 3.1] on a five-point scale; P
      <.05) and were more likely to report provision of cessation assistance than
      pediatric providers (63% [44%, 82%] versus 17% [5%, 29%]; P <.05). Obstetric
      providers were more likely to prescribe or recommend over-the-counter nicotine
      replacement therapy than pediatric providers (44% [25%, 63%] versus 11% [1%,
      21%], P =.004). Reasons for not prescribing nicotine replacement differed
      according to specialty; however, perceived lack of efficacy was not a typical
      reason given by clinicians in either specialty. Only two of 47 practitioners who
      did not prescribe or recommend those therapies listed that as a factor in their
      decisions. CONCLUSION: We found that nicotine replacement therapies are commonly
      prescribed or recommended to pregnant smokers by obstetric providers, but less
      commonly to lactating women by pediatric providers.

PMID- 10908775
TI  - Complications of hysteroscopy: a prospective, multicenter study.
AB  - OBJECTIVE: To estimate the incidence of complications of diagnostic and operative
      hysteroscopic procedures in the Netherlands and describe their nature. METHODS:
      Data on complications were recorded by 82 hospitals in 1997. Participating
      hospitals had a 100% response rate. Any unexpected events that required
      intraoperative or postoperative intervention were defined as complications in two
      groups: approach (entry-related) and technique-related (caused by surgical
      instruments). RESULTS: Thirty-eight complications occurred among 13,600
      hysteroscopic procedures (rate 0.28%). Diagnostic hysteroscopic procedures had a
      significantly lower complication rate (0.13%) than operative procedures (rate
      0.95%; P <.01). Fluid overloads of distention medium were recorded five times
      (rate 0.20%). The most frequent surgical complication was perforation of the
      uterine cavity (rate 0.76%). Approximately half the perforations (18 of 33) were
      entry-related. Bleeding caused by perforation was seen in 0.16% of cases.
      Incidences of complications were: intrauterine adhesiolysis 4.48%, endometrium
      resection 0.81%, myomectomy 0.75%, and removal of a polyp 0.38%. CONCLUSION:
      Diagnostic hysteroscopic procedures had very low complication rates, so are safe
      procedures with which to evaluate intrauterine pathology. Operative hysteroscopic
      procedures were more risky, but the removal of polyps had a very low complication
      rate (12 times lower than synechiolysis). Half the complications were entry
      related, so attention has to be paid to the method of entry with the hysteroscope
      (ie, no unnecessary dilation of cervix and introduction of the scope under direct
      vision). The other half of complications were related to surgeons' experience and
      type of procedure.

PMID- 10908776
TI  - Placental apoptosis in preeclampsia.
AB  - OBJECTIVE: To determine whether preeclampsia is associated with an increase in
      placental apoptosis and differential expression of mediators of apoptosis.
      METHODS: Placental samples from 31 preeclamptic women and 31 normotensive
      controls were analyzed using terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick-end labeling staining. Expression of Fas, Fas
      ligand, Bcl-2, and Bax was assessed using immunohistochemistry. RESULTS: The
      median percent apoptotic nuclei was significantly higher for the study group than
      for the controls (0.49 versus 0.19; P =.001), as was the median percent apoptotic
      nuclei in the trophoblast nuclei (0.33 versus 0.09; P <.01). Fas ligand
      expression was significantly less and Fas expression significantly greater in the
      villus trophoblast among the study subjects compared with controls. There was no
      difference in the expression of Bax or Bcl-2 between groups. CONCLUSION:
      Placental apoptosis and altered expression of Fas and Fas ligand in trophoblast
      might influence pathogenesis or sequelae of preeclampsia.

PMID- 10908777
TI  - 677 C-->T polymorphism of the methylenetetrahydrofolate reductase gene and
      preeclampsia.
AB  - OBJECTIVE: To evaluate C to T substitution at nucleotide 677 of N(5), N(10)
      methylenetetrahydrofolate reductase gene in women with prior preeclamptic or
      normotensive pregnancies. METHODS: Methylenetetrahydrofolate reductase genotypes
      were determined in 113 Finnish women with preeclamptic first pregnancies and 103
      controls with one or more normotensive pregnancies, using polymerase chain
      reaction and restriction enzyme analysis. Preeclampsia was defined as severe in
      100 women who fulfilled one or more of the subsequent criteria: systolic blood
      pressure (BP) at least 160 mmHg, diastolic BP at least 110 mmHg, or proteinuria
      at least 2 g per 24-hour urine collection. RESULTS: There were no significant
      differences in prevalences of the methylenetetrahydrofolate reductase genotypes
      (CC, CT, and TT) between groups (57%, 40%, and 3% in the preeclamptic group and
      54%, 39%, and 7%, respectively, in controls). The frequency of the T677 allele
      was 0.23 in the preeclamptic group and 0.26 in the control group (difference
      0.03; 95% confidence interval -0.08, 0.14; P =.51). Our sample had 60% power to
      detect a difference of the allele frequencies similar to that (0.12) reported
      previously. The result was similar when analysis was restricted to patients with
      severe preeclampsia (T677 allele frequency 0.22). CONCLUSION: A carrier status
      for the T677 allele of the methylenetetrahydrofolate reductase gene does not
      predispose to preeclampsia, at least in the Finnish population.

PMID- 10908778
TI  - Comparative genomic hybridization for cytogenetic evaluation of stillbirth.
AB  - OBJECTIVE: To ascertain the feasibility and reliability of comparative genomic
      hybridization for cytogenetic evaluation of macerated stillbirths. MATERIALS: We
      examined ten stillborn fetuses above 15 weeks' gestation whose karyotypes were
      unknown because of tissue culture failure. Sixteen fetuses that were successfully
      karyotyped using prenatal or postnatal tissues were also examined as controls,
      including five pregnancy terminations with autosomal aneuploidy, one with sex
      chromosome aneuploidy, one with a chromosomal deletion; five macerated fetuses
      with normal karyotypes, three with autosomal aneuploidy, and one with sex
      chromosome aneuploidy and discrepancy between chorionic villi and fetus. RESULTS:
      All comparative genomic hybridization analyses in fresh and macerated tissues
      were successful except for one. All normal karyotypes and aneuploidies were
      confirmed. Comparative genomic hybridization failed in one fetus with a deletion
      of the short arm of chromosome 18. In the stillborn fetuses without known
      karyotypes, one aberrant profile was found; however, the results were not
      confirmed with interphase fluorescence in situ hybridization. In one fetus
      triploidy was diagnosed with DNA flow cytometry. CONCLUSION: Comparative genomic
      hybridization is a valuable backup technique for aneuploidy screening in tissues
      from macerated stillborn fetuses when tissue culture fails. Gains or losses can
      subsequently be confirmed by fluorescence in situ hybridization, using DNA probes
      that focus on specific loci of a chromosome.

PMID- 10908779
TI  - Adrenal suppression induced by betamethasone in women at risk for premature
      delivery.
AB  - OBJECTIVE: To determine whether betamethasone administered to women at risk of
      preterm delivery causes adrenal suppression. METHODS: Ten women at risk of
      preterm delivery had three weekly low-dose (1 microg) ACTH stimulation tests with
      the first one between 24 and 25 weeks' gestation. Immediately after the first and
      second ACTH stimulation tests, we gave each woman a 12-mg betamethasone dose
      intramuscularly and repeated it 24 hours later. The third ACTH stimulation test
      was 1 week after the second course of betamethasone. Serum cortisol levels were
      measured before (baseline) and 30 minutes after ACTH administration. RESULTS: All
      subjects had normal baseline and stimulated cortisol levels for the first ACTH
      stimulation test. Mean baseline serum cortisol levels decreased with each ACTH
      stimulation test, from 25.4 +/- 4.8 microg/dL (before betamethasone) to 4.3 +/-
      4.0 microg/dL (1 week after the second course of betamethasone) (P <.001). The
      mean stimulated cortisol levels also decreased from 33.0 +/- 4.3 microg/dL
      (before betamethasone) to 11.8 +/- 6.4 microg/dL (1 week after the second course
      of betamethasone) (P <.001). Compared with initial ACTH stimulation tests,
      laboratory evidence of adrenal suppression occurred in four patients 1 week after
      the first course of betamethasone and in seven patients after the second course.
      No signs or symptoms of Addisonian crisis occurred antepartum or intrapartum.
      CONCLUSION: Antenatal administration of betamethasone produced measurable adrenal
      suppression in women at risk of preterm delivery. The number of women with
      adrenal suppression increased each week that antenatal betamethasone was
      repeated. (Obstet Gynecol 2000;96:287-90.)

PMID- 10908780
TI  - Forty weeks and beyond: pregnancy outcomes by week of gestation.
AB  - OBJECTIVE: To assess pregnancy outcomes at 40, 41, and 42 weeks' gestation when
      labor induction is done routinely at 42 but not 41 weeks. METHODS: We reviewed
      all singleton pregnancies delivered at 40 or more weeks' gestation between 1988
      and 1998 at Parkland Memorial Hospital, Dallas, Texas. We excluded women with
      hypertension, prior cesarean, diabetes, malformations, breech presentation, and
      placenta previa. Labor characteristics and neonatal outcomes of pregnancies at 41
      and 42 weeks' gestation were compared with pregnancies that ended at 40 weeks.
      Women with certain dating criteria had induction of labor at 42 weeks.
      Gestational age was calculated from the last menstrual period (LMP), sonography
      when available, and clinical examination. If the fundal height between 18 and 30
      weeks was within 2 cm of gestational age, the reported LMP was accepted as
      correct. Sonogram was used to calculate gestational age if a discrepancy was
      identified. Statistical analysis consisted of chi(2) and analysis of variance.
      RESULTS: We studied 56,317 pregnancies: 29,136 at 40 weeks, 16,386 at 41 weeks,
      and 10,795 at 42 weeks. Labor complications increased from 40 to 42 weeks,
      including oxytocin induction (2% versus 35%, P <.001), length of labor (5.5 +/-
      4.9 versus 8.8 +/- 6. 5 hours, P <.001), prolonged second stage of labor (2%
      versus 4%, P <.001), forceps use (6% versus 9%, P <.001), and cesarean delivery
      (7% versus 14%, P <.001). Neonatal outcomes were similar in the three groups,
      including 5-minute Apgar score less than 4, admission to the neonatal intensive
      care unit (NICU), umbilical artery pH less than 7, seizures, and perinatal
      mortality. Sepsis was more frequent in the 42-week group than the other groups
      (0.1 versus 0.3%, P =. 001), as was admission to the NICU (0.4 versus 0.6%, P
      =.008). CONCLUSION: Routine labor induction at 41 weeks likely increases labor
      complications and operative delivery without significantly improving neonatal
      outcomes.

PMID- 10908781
TI  - Clinical usefulness of white blood cell count after cesarean delivery.
AB  - OBJECTIVE: To examine changes in white blood cell (WBC) count after cesarean and
      estimate risk of postoperative infection. METHODS: We measured complete blood
      cell counts at admission and on postoperative day 1 for 458 women who had
      cesareans. Information from charts was abstracted, and definitions of infectious
      outcomes and fever were applied by three physicians masked to laboratory results.
      We examined changes in absolute and relative WBC counts by labor status.
      Likelihood ratios for postoperative infection were calculated for statistically
      distinct categories of percentage changes. RESULTS: We excluded 60 women with
      chorioamnionitis. Of the remainder, 34 (8.5%) developed endometritis and three
      (0.8%) pneumonia. Women who labored before cesarean (n = 198) had higher
      antepartum (P <.001) and postoperative day 1 (P <.001) WBC counts than those who
      did not (n = 200). However, change in WBC count after cesarean relative to
      antepartum was similar for both groups (P =.41), averaging a 22% increase. We
      grouped percentage changes into the following three levels: up to 24%, 25-99%,
      and at least 100%. The lowest level (n = 246) corresponded to a category-specific
      likelihood ratio for diagnosis of serious postpartum infection of 0. 5 (95%
      confidence interval [CI] 0.3, 0.8), the midlevel (n = 141) to a category-specific
      likelihood ratio of 1.7 (95% CI 1.2, 2.3), and the highest level (n = 11) to a
      category-specific likelihood ratio of 5.8 (95% CI 1.8, 18.7). CONCLUSION: Labor
      influenced postcesarean WBC counts but did not obscure changes associated with
      infection. Information gained from changes in WBC counts can be used to assess
      risk of infection.

PMID- 10908783
TI  - Model of family medicine and obstetrics-gynecology collaboration in obstetric
      care at the University of Michigan.
AB  - OBJECTIVE: To assess concordance between family physician obstetric privilege
      delineation and actual care delivered, and describe associated clinical and
      educational collaborations between family medicine and obstetrics and gynecology.
      METHODS: We conducted a descriptive retrospective review of the care and
      complications of 962 consecutive patients admitted to a family medicine obstetric
      service in a research-intensive academic medical center, and compared the results
      with a structured obstetric privilege delineation. RESULTS: Of 962 women admitted
      by family medicine faculty members, 741 (77.9%) were managed exclusively by
      family physicians, 63 (6.6%) were comanaged by family physicians and
      obstetricians, and 147 (15.5%) were transferred to obstetricians (data missing
      for 11 patients). Spontaneous vaginal deliveries were performed in 772 patients
      (81%), cesarean delivery in 116 patients (12.2%), and assisted delivery by
      forceps or vacuum in 19 (2%) and 44 (4.6%) patients, respectively. Of 926
      intrapartum obstetric complications identified in 604 obstetric deliveries, 615
      complications (66.4%) in 418 deliveries were managed exclusively by family
      physicians consistent with privilege delineation, comanagement occurred in 56
      patients with 92 complications (9.9%), and care was transferred in 130 patients
      with 219 complications (23. 7%). CONCLUSION: A structured method of obstetric
      privilege delineation for family medicine faculty members and associated
      guidelines for family physician-obstetrician interactions has led to a successful
      family medicine obstetric service at a research-intensive, tertiary-care medical
      center, with a high concordance between privilege delineation and actual care
      delivered. This success has resulted in incremental clinical and educational
      collaborations that have improved the quality of women's health care and
      education.

PMID- 10908782
TI  - Fungal culture findings in cyclic vulvitis.
AB  - OBJECTIVE: To estimate the prevalence of fungal infection in cyclic vulvitis.
      METHODS: We retrospectively reviewed 40 cases of cyclic vulvitis. We examined the
      historic characteristics, physical findings, and laboratory results in this
      population, including the results of potassium hydroxide preparations of vaginal
      secretions and fungal cultures. RESULTS: The median age was 32 years and the mean
      duration of symptoms was 3.8 years. Thirty women (75%) reported prior antifungal
      therapies. Fungal cultures were positive in 24 of 39 (61.5%). Candida albicans
      was the species isolated in 13 of 24 cases (54%). Potassium hydroxide wet mounts
      contained evidence of fungal infection in 15 of 37 cases (40.5%). The sensitivity
      of the potassium hydroxide preparation was only 61%. Potassium hydroxide
      preparations were more sensitive when the species isolated was C albicans.
      CONCLUSIONS: Many women with cyclic vulvitis have positive vaginal fungal
      cultures. Potassium hydroxide preparations of vaginal secretions are not
      sufficiently sensitive to exclude fungal infection in this setting, possibly
      because of the relatively high incidence of fungal species other than C albicans.
      Fungal culture should be considered in the evaluation of women with recurrent
      episodes of vulvar discomfort, even when potassium hydroxide wet mounts do not
      contain fungal elements.

PMID- 10908784
TI  - The obstetric trials and tribulations of Dr. John Mackieson, Charlottetown,
      Prince Edward Island, 1827-1857.
AB  - For 30 years, from 1827 to 1857, Dr. John Mackieson, a medical practitioner in
      Charlottetown, Prince Edward Island, Canada, kept a detailed account of
      complicated obstetric cases. An analysis of this casebook provides a unique
      profile of obstetric complications and their management in eastern Canada 150
      years ago. The main causes of maternal death were puerperal sepsis and
      hemorrhage. The reported perinatal deaths most often were associated with
      traumatic vaginal delivery.

PMID- 10908785
TI  - Pollen morphology, exine structure, and systematics of Acalyphoideae
      (Euphorbiaceae), part 3. Tribes Epiprineae (Epiprinus, Symphyllia, Adenochlaena,
      Cleidiocarpon, Koilodepas, Cladogynos, Cephalocrotonopsis, Cephalocroton,
      Cephalomappa), Adelieae (Adelia, Crotonogynopsis, Enriquebeltrania, Lasiocroton,
      Leucocroton), Alchorneae (Orfilea, Alchornea, Coelebogyne, Aparisthmium,
      Bocquillonia, Conceveiba, Gavarretia), Acalypheae pro parte (Ricinus, Adriana,
      Mercurialis, Leidesia, Dysopsis, Wetria, Cleidion, Sampantaea, Macaranga).
AB  - This is the third paper of an extensive study of pollen morphology and exine
      structure of Acalyphoideae (Euphorbiaceae) following the most recent system of
      Webster. Pollen from 120 collections representing 96 species and 30 genera is
      described and illustrated with light microscopy, scanning and transmission
      electron microscopy. These taxa are from tribes Epiprineae, Adelieae, Alchorneae,
      and Acalypheae pro parte. Pollen of eight genera, Epiprinus, Symphyllia,
      Adenochlaena, Cleidiocarpon, Koilodepas, Cladogynos, Cephalocrotonopsis and
      Cephalocroton, of the nine assigned to Epiprinae share 3-colporate apertures,
      microreticulate, punctate or deeply punctate tecta, well developed or prominent
      columellae (Koilodepas excepted) and thin foot layers; pollen of the ninth genus,
      Cephalomappa, has porelike colpi, a coarsely reticulate exine, irregular
      columellae and an irregular foot layer. Of the five genera assigned to Adelieae,
      pollen of Adelia, Lasiocroton and Leucocroton is similar: 3-colp(oroid)ate with
      stratified opercula, crotonoid tecta and thin foot layers; grains of
      Enriquebeltrania and Crotonogynopsis lack opercula and the latter has a
      distinctive infratectum of poorly differentiated columellae. All genera examined
      of tribe Alchorneae, seven of the nine, have exines with unstratified opercula
      and elongated columellae near the endoaperture. Exines of subtribe Alchorneinae
      (Orfilea, Alchornea, Coelebogyne, Aparisthmium, Bocquillonia) have complex
      infratecta of poorly differentiated columellae, whereas pollen of Conceveiba and
      Gavarretia, the two genera examined of the three assigned to subtribe
      Conceveibinae, has a single layer of short columellae and almost identical tectal
      morphology. In the large tribe Acalypheae, pollen of the first six of the 11
      subtribes was examined. Pollen of Ricinus (Ricininae) and Adriana (Adrianinae)
      share indistinguishable exine structures and tecta. Pollen of Mercurialis and
      Leidesia of subtribe Mercurialinae and pollen of Dysopsis of subtribe
      Dysopsidinae are almost identical: finely reticulate tecta, very thin apertural
      endexines, elongate columellae, and channeled/perforate foot layers. All three
      genera of subtribe Cleidiinae have grains that are 3-colporate and have complete
      tecta; pollen of Wetria has a tectum morphology very similar to that of Ricinus
      and Adriana; pollen of Cleidion is 3-brevicolporate with microrugulose or
      punctate tecta, and has threadlike non-apertural endexines and foot layers, and
      thick tecta; exines of Sampantaea have an endexine throughout the grain, thin
      foot layers, very short columellae and a thick continuous tectum. Pollen of
      Macaranga of subtribe Macaranginae is small, 3-colporate with poorly defined
      endoapertures, and an exine structure characterized by thin foot layers, short
      columellae, and thick tecta. Pollen data support: the concept of the subtribe
      Epiprininae, but indicate that subtribe Cephalomappinae (Cephalomappa) is not
      related and should be considered for separate tribal status; a close relationship
      among Adelia, Lasiocroton and Leucocroton, but not with the two remaining members
      of Adelieae, Enriquebeltrania and Crotonogynopsis, which do not appear to be
      closely related to each other; the present concept of Alchorneae and subtribes
      Alchorneinae and Conceveibinae. Within the genera examined of the first six
      subtribes of Acalypheae, the pollen data: support a close relationship between
      the monogeneric subtribes Ricininae and Adrianinae; indicate a close relationship
      between subtribes Mercurialinae (Mercurialis, Leidesia) and Dysopsidinae
      (Dysopsis); suggest that Wetria is not closely related to Cleidion or Sampantaea
      (Cleidiinae); tentatively support the concept of Macaranginae as comprising only
      Macaranga.

PMID- 10908786
TI  - Leaf morphology and cuticular features of Sphenophyllum in the Gigantopteris
      flora from South China.
AB  - Permian specimens of Sphenophyllum with preserved cuticular anatomy have been
      discovered in Cathaysia and have prompted a detailed re-evaluation of the genus
      in the Gigantopteris flora in South China. New specimens are described and
      previously published material is re-examined to clarify taxonomic diversity and
      to establish geographic and stratigraphic ranges for each species. Recognized
      taxa include Sphenophyllum apiciserratum sp. nov., S. koboense Kobatake, S.
      meridionale sp. nov., S. minor (Sterzel) Gu and Zhi, S. sinocoreanum Yabe, S. cf.
      sinocoreanum Yabe, and S. aff. speciosum (Royle) McClelland. Cuticles of
      Sphenophyllum apiciserratum and S. koboense are hypostomatic with randomly
      disposed ordinary cells in intercostal regions. Specific concepts are clarified
      and unresolved taxonomic problems are discussed. The South China taxa are
      compared with those from Euramerican, Gondwanan and Angaran floras, and the South
      China Cathaysian species are found to be taxonomically distinct.

PMID- 10908787
TI  - Two unusual new dinoflagellate cyst genera from the Bunde Borehole, Maastrichtian
      type area, southern Netherlands.
AB  - Maastrichtian and Danian deposits from the Bunde Borehole in the Maastrichtian
      type area contain the morphologically unusual dinoflagellate species Spumadinium
      felderorum gen. et sp. nov. and Lasagniella herngreenii gen. et sp. nov., both of
      which have archeopyles formed by the loss of several paraplates. In S. felderorum
      the paraplates forming the operculum or opercular pieces appear to be the third
      and fourth precingulars (3"-4") plus the first and second anterior intercalaries
      (1a-2a). This suggests that Spumadinium, although having a wall resembling some
      cribroperidinioids, is a cladopyxiinean. L. herngreenii is unique in having up to
      eight wall layers, separated and supported by buttresses. The archeopyle is also
      a combination type but formed by loss of one apical (3'), three anterior
      intercalary (1a-3a) and three precingular (3"-5") paraplates. Thus, Lasagniella
      is assignable to the Peridiniales. The distinctive morphology and restricted
      ranges of the two genera make them useful stratigraphic markers for the Upper
      Maastrichtian-Danian.

PMID- 10908789
TI  - Editorial

PMID- 10908788
TI  - Vegetation stability in the Southeastern Brazilian coastal area from 5500 to 1400
      14C yr BP deduced from charcoal analysis.
AB  - Charcoal analysis of six shell mounds showed that no major changes of the
      mainland vegetation ecosystem have taken place along the southeastern Brazilian
      coast (22 degrees 53'-22 degrees 57'S, 42 degrees 03'-42 degrees 33'W) from 5500
      to 1400 14C yr BP. These shell mounds have been occupied by sedentary fisher
      gatherer-hunters. Charcoal fragments retrieved from vertical profiles in the
      archaeological sites were examined; taxonomic determinations were based on a
      reference collection of charred woods and a program for computer-aided
      identification. Charcoal assemblages of all the studied sites present taxa from
      various restinga vegetation types, mangroves, xeromorphic coastal forest, and
      inland Atlantic Forest. The restinga ecosystem, characteristic of the Brazilian
      coast, is associated with sandy beach ridges; the restinga forest was much more
      abundant during the studied period than nowadays. The charcoal assemblages
      represent mainly the local vegetation; a regional reconstruction depends on the
      study of numerous sites. In the Cabo Frio region, open restinga taxa are more
      abundant in the Sambaqui do Forte, while forest elements are more important in
      the Sambaquis Salinas Peroano and Boca da Barra. The sites studied in the Arraial
      do Cabo (Sambaqui da Ponta da Cabeca) and in the Saquarema regions (Sambaquis da
      Pontinha and da Beirada) show that open restinga formations were locally
      predominant. A comparison of multivariate analysis applied to both charcoal
      assemblages and to phytosociological data of the extant vegetation showed a good
      correspondence between the charcoal spectra and the present vegetation. The high
      taxonomic diversity of archaeological charcoal samples and numerous fragments
      showing traces of decay before charring suggests that aleatory gathering of dead
      wood constituted the main source of firewood for fisher-gatherer-hunters
      populations. Condalia sp. was probably selected for cultural reasons.The only
      significant fluctuations on the charcoal spectra relate to the mangrove
      vegetation. Two relatively humid episodes (recorded from ca. 5500 to 4900/4500
      and from ca. 2300 to 2000 14C yr BP), intercalated by two episodes of increased
      dryness with increased lagoon salinity (from ca. 4900/4500 to 2300 and from ca.
      2000 to 1400 14C yr BP) were recorded in the Cabo Frio region. The changes in
      mangrove vegetation cannot be attributed to sea-level variations, for the three
      regressive and the two transgressive episodes identified for the Brazilian coast
      during this period are not in phase with the development of mangroves. The
      stability of the mainland vegetation ecosystem is probably due to the edaphic
      character of the coastal environments, which makes coastal formations much more
      resistant to climatic variations and less sensitive to climatic change. We
      propose that this environmental stability was a decisive factor in the
      maintenance of the fisher-gatherer-hunter sociocultural system.

PMID- 10908791
TI  - Metabolically optimised BHK cell fed-batch cultures.
AB  - The aim of this work was the optimisation of a fed-batch culture by metabolic
      confinement of BHK21 cells producing an antibody/cytokine fusion protein with
      potential application in tumour-targeted therapy. Previous results showed that at
      very low nutrient concentrations, a metabolic shift towards more efficient
      metabolic pathways occurs. The application of those results in the optimisation
      of a fed-batch culture resulted in higher cell growth (0.020 vs. 0.016 h(-1)) and
      cell viability, higher maximum cell concentration (2.5 vs. 1.1x10(6) cell ml(
      1)), longer culture span (17 versus nine days) and higher product titre (60%
      increase), in relation to batch culture. This was achieved by maintaining glucose
      at 0.3 mM and glutamine at 0.2 mM through the addition of a concentrated solution
      based on the estimations of future nutrient consumption and growth rates through
      off line measurements. The production of toxic metabolites such as lactate and
      ammonia was reduced, especially the lactate production, which was markedly
      decreased due to the metabolic confinement of the cells. In conclusion, it was
      possible to increase the final titre of the recombinant antibody/cytokine fusion
      protein by confining the metabolism of the cells to an energetically more
      efficient state.

PMID- 10908790
TI  - A repeat-batch membrane bioreactor with a phase inversion for the desaturation of
      isopropyl palmitate by a mutant Rhodococcus strain.
AB  - A repeat-batch membrane bioreactor was constructed for the novel bioconversion of
      isopropyl hexadecanoate to isopropyl cis-6-hexadecenoate by a Rhodococcus mutant.
      The addition of glutamate, thiamine, and MgSO(4) was very effective in improving
      not only the rate and yield of the bioconversion but also the maintenance of
      desaturation activity during cell recycling. An oil-in-water (O/W) type emulsion
      of the reaction medium was inverted to a water-in-oil (W/O) type by discharging
      the water phase from the reaction mixture. The continuous oil phase containing
      the product could effectively be recovered through a hydrophobic hollow-fiber
      module. By decreasing the oil-to-water ratio upon addition of fresh medium, the
      medium was spontaneously inverted again to an O/W type emulsion to proceed with
      the next conversion. The batch reaction coupled with the phase inversion could be
      repeated more than 13 times for over about 300 h operation. Finally, a highly
      purified product was obtained with high yield by the urea adduct procedure.

PMID- 10908792
TI  - Growth of Candida boidinii on methanol and the activity of methanol-degrading
      enzymes as affected from formaldehyde and methylformate.
AB  - Formaldehyde and methylformate affect the growth of Candida boidinii on methanol
      and the activity of methanol-degrading enzymes. The presence of both
      intermediates in the feeding medium caused an increase in biomass yield and
      productivity and a decrease in the specific rate of methanol consumption. In the
      presence of formaldehyde, the activity of formaldehyde dehydrogenase and formate
      dehydrogenase was essentially increased, whereas the activity of methanol oxidase
      was decreased. On the contrary, the presence of methylformate caused an increase
      of the activity of methanol oxidase and a decrease of the activity of
      formaldehyde dehydrogenase and formate dehydrogenase. Interpretations concerning
      the yeast behavior in the presence of intermediate oxidation products were
      considered and discussed.

PMID- 10908793
TI  - Hydrolysis of isolated coffee mannan and coffee extract by mannanases of
      Sclerotium rolfsii.
AB  - Different mannanase preparations obtained from the filamentous fungus Sclerotium
      rolfsii were used for the hydrolysis of coffee mannan, thus reducing
      significantly the viscosity of coffee extracts. Mannan is the main polysaccharide
      component of these extracts and is responsible for their high viscosity, which
      negatively affects the technological processing of instant coffee. Coffee mannan
      was isolated from green defatted Arabica beans by delignification, acid wash and
      subsequent alkali extraction with a yield of 12.8%. Additionally, coffee extract
      polysaccharides were separated by alcohol precipitation and were found to form
      nearly half of the coffee extract dry weight. These isolated mannans as well as
      the mannan in the coffee extract were efficiently hydrolysed by the S. rolfsii
      mannanase, which resulted in significant viscosity reductions. Concurrently, the
      reducing sugar content increased continuously due to the release of various
      mannooligosaccharides including mannotetraose, mannotriose, and mannobiose. Both
      a partially purified, immobilised and a soluble, crude mannanase preparation were
      successfully employed for the degradation of coffee mannan.

PMID- 10908794
TI  - Improved secondary metabolite production in the genus Streptosporangium by
      optimization of the fermentation conditions.
AB  - The cultivation of strains of the genus Streptosporangium in batch fermentations
      demonstrated that the optimal conditions for secondary metabolite production are
      completely different to those of the closely related genus Streptomyces. The
      dissolved oxygen tension (pO(2)) was identified as an important parameter for
      optimal production of secondary metabolites in submerged cultures. Extreme
      variations of this parameter by changes in aeration (gas flow), agitation system
      and stirrer speed showed a tremendous impact in production yields of all
      investigated strains. Finally, a 20-fold increase in productivity was observed by
      conditions of controlled oxygen excess compared to optimal fermentation
      conditions for Streptomyces strains.

PMID- 10908795
TI  - High-throughput protein expression of cDNA products as a tool in functional
      genomics.
AB  - A proteomics approach has been developed aimed to allow high throughput analysis
      of protein products expressed from cDNA fragments (expressed sequence tags,
      ESTs). The concept relies on expression of gene products to generate specific
      antibodies for protein analysis, such as immunolocalization of the proteins on
      cellular and subcellular level. To evaluate the system, 55 cDNA clones with
      predominantly unknown function were selected from a mouse testis cDNA-library. A
      bacterial expression system was designed that allowed robust expression and easy
      purification. Protein levels between 15 and 80 mg l(-1) were obtained for 49 of
      the clones. Five clones were selected for immunization and all yielded functional
      antibodies that gave specific staining in Western blot screening of samples from
      various cell types. Furthermore, extensive immunolocalization information on
      subcellular level was obtained for three of the five clones. All generated data
      were stored in a relational database, and are made available through a web
      interface (http://www.biochem.kth.se/multiscale/), which also provides relevant
      links and allows homology searches from the original sequences. The possibility
      to allow analysis of gene products from whole genomes using this 'localization
      proteomics' approach is discussed.

PMID- 10908796
TI  - Statistical analysis of elicitation strategies for thiarubrine A production in
      hairy root cultures of Ambrosia artemisiifolia.
AB  - Elicitation strategies were studied for yield enhancement of thiarubrine A, a
      secondary metabolite and a potential pharmaceutical, produced by hairy root
      cultures of Ambrosia artemisiifolia. Abiotic elicitation was performed using
      vanadyl sulfate solution and biotic elicitation using autoclaved cell wall
      filtrates of the fungi Protomyces gravidus, a pathogen of A. artemisiifolia and
      Botrytis cinereae. The factors considered were age of the culture, concentration
      of the elicitor used and the time period of exposure or contact. Statistical
      methods were used to determine the strength of the interaction between the
      various factors and their response on the yield of the secondary metabolite. The
      maximum increase in the yield relative to the control, 8-fold corresponding to
      569 microg g(-1) of biomass, was observed when 16-day-old cultures were elicited
      with 50 mg l(-1) of vanadyl sulfate for a time period of 72 h. The maximum yield
      of 647 microg g(-1) was achieved when the cultures were exposed to 5 microM
      autoclaved cell wall filtrates of P. gravidus for a time period of 48 h. The
      yield increase was 3-fold in the case of elicitation with autoclaved cell wall
      filtrates of B. cinereae. The methodology used in this report can be extended to
      determine the optimum conditions of other elicitors.

PMID- 10908797
TI  - Stability towards alkaline conditions can be engineered into a protein ligand.
AB  - One of the problems with a proteinaceous affinity ligand is their sensitivity to
      alkaline conditions. Here, we show that a simple and straightforward strategy
      consisting in replacing all asparagine residues with other amino acids can
      dramatically improve the chemical stability of a protein towards alkaline
      conditions. As a model, a Streptococcal albumin-binding domain (ABD) was used.
      The engineered variant showed higher stability towards 0.5 M NaOH, as well as
      higher thermal stability compared to its native counterpart. This protein
      engineering approach could potentially also be used for other protein ligands to
      eliminate the sensitivity to alkaline cleaning-in-place (CIP) conditions.

PMID- 10908798
TI  - Immobilized soy-sauce yeasts: development and characterization of a new
      polyethylene-oxide support.
AB  - Entrapment of cells in alginate gel is a widely used mild immobilization
      procedure. However, alginate gel is not very suitable for use in long-term
      continuous soy-sauce processes because alginate is sensitive to abrasion and
      chemically unstable towards the high salt content of soy-sauce medium. Therefore,
      a chemically crosslinked polyethylene-oxide gel was used instead. The
      disadvantage of this gel was that due to the crosslinking reaction, the viability
      of the cells after immobilization was poor. For this reason, a new mild procedure
      for immobilizing soy-sauce yeasts in polyethylene-oxide gel was developed,
      resulting in high survival percentages of the soy-sauce yeasts Zygosaccharomyces
      rouxii and Candida versatilis. This newly developed polyethylene-oxide gel,
      unlike alginate gel, appeared not to be sensitive to abrasion, even in the
      presence of high salt concentrations. Therefore, we concluded that this newly
      developed polyethylene-oxide gel is more suitable than alginate gel for use as
      immobilization material in long-term processes with a high salt content, like soy
      sauce processes.

PMID- 10908799
TI  - Continuous ethanol production from pineapple cannery waste using immobilized
      yeast cells.
AB  - The cells of Saccharomyces cerevisiae ATCC 24553, were immobilized in k
      carrageenan and packed in a tapered glass column reactor for ethanol production
      from pineapple cannery waste at temperature 30 degrees C and pH 4.5. The maximum
      productivity was 42.8 g ethanol 1(-1) h(-1) at a dilution rate of 1.5 h(-1). The
      volumetric ethanol productivity of the immobilized cells was ca. 11.5 times
      higher than the free cells. The immobilized cell reactor was operated over a
      period of 87 days at a dilution rate of 1.0 h(-1), without any loss in the
      immobilized cell activity. The maximum specific ethanol productivity and specific
      sugar uptake rate of the immobilized cells were 1.2 g ethanol g(-1) dry wt. cell
      h(-1) and 2.6 g sugar g(-1) dry wt. cell h(-1), respectively, at a dilution rate
      of 1.5 h(-1).

PMID- 10908801
TI  - Expression of thaumatin-like permatin PR-5 genes switches from the ovary wall to
      the aleurone in developing barley and oat seeds.
AB  - Permatins are antifungal thaumatin-like proteins (TLPs) of the PR-5 family of
      pathogenesis-related proteins. They occur in many cereals, but little is known of
      their expression and roles. Permatin cDNA clones were produced and used to study
      expression in developing barley and oat seeds. Actin and CDC48 mRNAs declined
      rapidly following inoculation of barley spikes with Fusarium graminearum. Despite
      this, permatin mRNA levels remained constant or increased slightly. Studies of
      permatin gene expression in healthy plants revealed that developing barley and
      oat seeds accumulate permatin mRNA in an unusual bimodal pattern. Permatin mRNA
      and protein are highly abundant around the time of pollination and then decrease
      rapidly to near-zero. A second peak occurs in the doughy stage of development.
      Antibody and DNA probe hybridization studies showed that expression initially
      occurs in the ovary wall and then switches to the aleurone and ventral furrow of
      developing seeds, reaching a peak in the doughy stage. Small amounts of permatin
      mRNAs also occur in certain vegetative tissues. The barley and oat permatin
      sequences provided sufficient comparisons between cereal TLPs to suggest that
      deletions or additions in specific elements could have led to the divergence of
      leaf- and seed-specific TLPs.

PMID- 10908800
TI  - Mercury-induced oxidative stress in tomato seedlings.
AB  - Mercury content and distribution as well as its effects on growth and oxidative
      stress were investigated in 30-day-old tomato seedlings (Lycopersicon esculentum
      Mill.). The content of Hg increased with external Hg concentrations, and was
      considerably higher in roots than in shoots. Among the leaves, the mature leaves
      accumulated more. Excess Hg suppressed biomass production of both roots and
      shoots and reduced chlorophyll content in leaves. Further, substantial increases
      of H(2)O(2) content, malondialdehyde formation, and antioxidant enzyme activities
      such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POX) were
      observed in Hg-stressed plants in comparison with controls. The results suggest
      that the phytotoxic effects of Hg in tomato seedlings may be achieved by an
      enhanced production of active oxygen species (AOS) and subsequent lipid
      peroxidation.

PMID- 10908802
TI  - Salinity induced behavioural changes in malate dehydrogenase and glutamate
      dehydrogenase activities in rice seedlings of differing salt tolerance.
AB  - The activities of malate dehydrogenase in whole tissue extract (NAD(+)-MDH) as
      well as in mitochondrial (NAD(+)-MDH) and chloroplastic (NADP(+)-MDH)
      preparations of aminating (NADH-GDH) and deaminating(NAD(+)-GDH) glutamate
      dehydrogenases were studied in two sets of rice cultivars differing in salt
      tolerance grown under moderate (7 dS m(-1)) and high (14 dS m(-1)) NaCl salinity
      levels. A contrasting response to salinity on enzyme activities was found between
      the sensitive and tolerant cultivars during a 5-20-day growth period of study.
      NaCl salinity in situ caused increase in all three MDH activities in salt
      tolerant cvs. CSR-1 and CSR-3 whereas in salt sensitive cvs. Ratna and Jaya 16
      100% inhibition in activities was noted. Chloroplastic MDH was extremely
      sensitive to NaCl. In seedlings of salt tolerant cultivars concomitant increase
      in both aminating and deaminating GDH activities was observed with increase in
      salinity level, whereas in sensitive cultivars under higher salinity level
      decrease in GDH activity was noted. Under in vitro conditions NaCl concentration
      in the range 1-1000 mM caused gradual inhibition in MDH activity. With 400 mM
      NaCl in vitro, complete loss of mitochondrial and chloroplastic MDH activities
      was observed. GDH activity increased with increasing concentration of NaCl up to
      200 mM NaCl and other salts in vitro and was inhibited thereafter. However 800 mM
      NaCl caused complete loss of deaminating GDH activity from sensitive cultivar but
      not from tolerant cultivar. Results suggest varying behaviour of MDH and GDH in
      two sets of rice cultivars differing in salt tolerance and that inhibition in the
      activities of dehydrogenases in salt sensitive rice cultivars due to salinity may
      be one of the possible reasons for decreased growth of rice plants under saline
      conditions.

PMID- 10908803
TI  - Accumulation and nuclear targeting of BnC24, a Brassica napus ribosomal protein
      corresponding to a mRNA accumulating in response to cold treatment.
AB  - Previously, we described two cDNA clones corresponding to a new family of cold
      regulated genes, pBnC24a and pBnC24b homologous to the human BBC1 (Breast Basic
      Conserved) gene. In order to further analyze the function and regulation of these
      two genes we have prepared antibodies against a recombinant fusion protein, MBP
      BnC24A and used them to study expression at the protein level. In contrast to the
      increased mRNA accumulation induced by cold, immuno-blot analysis showed that the
      quantity of the BnC24 protein was not correlated with the accumulation of BnC24
      transcripts and is identical in both control and low temperature treated (4
      degrees C) plants, suggesting a translational or post-translational regulation.
      This was confirmed by overexpressing BnC24 in transgenic Arabidopsis thaliana
      plants. Despite a substantial increase in mRNA, the BnC24 protein level is
      unchanged. In addition, we demonstrated by subcellular fractionation and
      immunodetection that a significant fraction of BnC24 protein is located in the
      nucleus. Using a GUS fusion construction and biolistic experiments it was found
      that a portion of the amino terminal region is sufficient to target this protein
      to the nucleus. These results are consistent with the recent finding that BBC1
      and its homologues code for the ribosomal large subunit protein L13. In addition
      they illustrate the difficulty of correlating accumulation of a given mRNA in
      response to a given stimulus with a biologically significant role in the
      adaptation to a new environment.

PMID- 10908804
TI  - The cold dependent accumulation of COR TMC-AP3 in cereals with contrasting, frost
      tolerance is regulated by different mRNA expression and protein turnover.
AB  - The accumulation of specific cold-regulated (COR) proteins is a component of the
      hardening process and different amount of COR proteins has been related to
      different degrees of cold tolerance. A number of different mechanisms controls
      the accumulation of the COR proteins in the plant cells. In this work we describe
      the mechanisms controlling the accumulation of the COR protein TMC-AP3, a
      putative chloroplastic amino acid selective channel protein [1] in barley, durum,
      wheat, emmer and bread wheat. Winter barley and, to less extent, winter bread
      wheat showed a higher cor tmc-ap3 expression at low temperature than the spring
      one while no significant differences were detected between the emmer and the
      durum. wheat genotypes. After 2 days of de-hardening the transcript level dropped
      down in the same way in all tested genotypes, nevertheless the decrease in
      protein content was genotype dependent. In all frost resistant genotypes the
      amount of COR TMC-AP3 after 9 days of de-hardening was higher compared with that
      of susceptible ones. These findings suggest that resistant and susceptible
      genotypes have different protein degradation rate and/or mRNA translational
      efficiency. Differences in the protein degradation rate were not dependent from
      the amino acidic sequence of the protein, being extremely similar in all tested
      genotypes. A genetic study based on Chinese spring/Cheyenne chromosome
      substitution lines showed that the turnover of TMC-AP3 is a polygenic trait
      controlled by a number of loci being the most important located on chromosomes
      1B, 2B, 2D and 4D.

PMID- 10908805
TI  - Glycosylation of the cationic peanut peroxidase gene expressed in transgenic
      tobacco.
AB  - The major cationic peanut (Arachis hypogaea) peroxidase, secreted into the
      extracellular space, is a glycoprotein with three N-linked glycans
      (polysaccharides) which are connected to the peptide backbone at Asn-60, Asn-144
      and Asn-185. In this report, a C-terminal histidine-tagged cationic peanut
      peroxidase gene was expressed in transgenic tobacco (Nicotiana tabacum). Tissue
      of the transgenic tobacco was cultured in suspension culture and the his-tagged
      peroxidase was purified in large quantities from 14-day-old suspension culture.
      The number of glycans, glycosylation sites and the chemical nature of glycan
      moieties attached to cationic peanut peroxidase expressed in transgenic tobacco
      were examined. Cationic peanut peroxidase isolated from the above transgenic
      tobacco had the identical number of complex glycans, attached at the same
      glycosylation sites as on cationic peanut peroxidase isolated from peanut
      suspension culture. Monosaccharide components of these glycans are N
      acetylglucosamine (GlcNAc), mannose (Man), fucose (Fuc), xylose (Xyl) and
      galactose (Gal), the same sugars as found in native cationic peanut peroxidase.

PMID- 10908806
TI  - Cytoskeletal inhibitors suppress the stomatal opening of Vicia faba L. induced by
      fusicoccin and IAA.
AB  - Stomatal movement is governed by osmotic potential, in which K(+) concentration
      plays the dominant role. Our previous work has shown that both microtubules and
      microfilaments are involved in regulating stomatal movement. In the present
      investigation the relationships between cytoskeletal components and K(+) fluxes
      in stomatal opening were addressed by using fusicoccin (FC), indoleacetic acid
      (IAA), and cytoskeletal inhibitors to treat both epidermal strips and protoplasts
      of guard cells. The results revealed that FC and IAA induced stomatal opening
      with or without KCl in the dark. Also FC or IAA induced guard cell protoplast
      swelling in the dark even without added KCl. However, the induction was partially
      suppressed when strips and protoplasts were pretreated with cytochalasin B (CB),
      an inhibitor of F-actin polymerization, or oryzalin, an inhibitor of plant
      microtubule polymerization. Thus our preliminary results indicate for the first
      time that microtubules and microfilaments can affect stomatal opening
      independently of K(+) fluxes.

PMID- 10908807
TI  - Structural and ultrastructural analysis of root primordia in vitro cultures (RPC)
      of Solanum lycopersicoides Dun.
AB  - The structure and ultrastructure of cell aggregates and derived root primordia
      were analysed in established suspension cultures of Solanum lycopersicoides Dun.
      A total of four modified Murashige and Skoog (1962) (MS) media were used, two
      containing alpha-naphthaleneacetic acid (NAA) and two containing 2,4
      dichlorophenoxyacetic acid (2,4-D). Considerable differences were observed in the
      size and structure of the aggregates regardless of the medium. The largest
      aggregates had a four-zone structure (cover, starch, dividing and differentiation
      zones) with distinct ultrastructural organization. The degree of histological and
      ultrastructural differentiation in the aggregates indicated rhizogenesis
      initiation. It begins with the protrusion of mounds of root primordia, which are
      the result of radial growth of cells in defined zones of the aggregate. Further
      growth from the primordium forms a root meristem with three tiers initial centre
      and wholly distinguished histogens (dermatogen, periblem, plerome). Rhizogenesis
      was more regular on media with NAA than on media with 2,4-D. Primordia and fully
      organized roots were liberated due to fragmentation of the aggregate and
      underwent changes in the permanently active developmental cycle of the culture
      which gave rise to successive generations of aggregates. Growth regulators had
      different influences on the organellar composition and phenolic compounds
      presence in the different zones of aggregates.

PMID- 10908808
TI  - High frequency of cytogenetic aberration in transgenic oat (Avena sativa L.)
      plants.
AB  - Cytological abnormalities were observed in transgenic oat (Avena sativa L. cv.
      GAF/Park-1) produced by microprojectile bombardment of mature seed-derived highly
      regenerative tissues. Of the plants from 48 independent transgenic lines
      examined, plants from only 20 lines (42%) were karyotypically normal (2n=6x=42)
      without detectable chromosomal aberrations; plants from 28 lines (58%) had
      chromosomal variation, i.e. aneuploids and structural changes. No significant
      difference in cytological aberration was observed between the two different
      culturing systems used for transformation: 57% chromosomal abnormalities in
      plants derived from D'BC2 medium (2.0 mg/l 2,4-D, 0. 1 mg/l BAP and 5.0 uM cupric
      sulfate) used for tissue initiation and maintenance and 60% in plants from tissue
      initiated on D'BC2 and maintained on DBC3 (1.0 mg/l 2,4-D, 0.5 mg/l BAP and 5.0
      uM cupric sulfate). Comparative differences in chromosomal status frequently
      occurred among plants regenerated from the same T(0) line. The most common
      cytological aberration in transgenic plants was aneuploidy, followed by deletion
      of chromosomal segments; no change in ploidy level was observed. In contrast,
      nontransgenic plants, regenerated from tissues comparable in age and culture
      media to that used for transgenic tissues, had a much lower percentage of
      karyotypic abnormality (0-14%). Our data indicate that some stress(es) imposed by
      the transformation process, e.g. osmotic treatment, bombardment and selection,
      leads to cytological variation in transgenic oat plants, an observation similar
      to that observed in our recent studies with transgenic barley plants.

PMID- 10908809
TI  - Possible involvement of a 72-kDa polypeptide in nucleotide excision repair of
      Chlorella pyrenoidosa identified by affinity adsorption and repair synthesis
      assay.
AB  - A DNA repair synthesis assay monitoring nucleotide excision repair (NER) was
      established in cell-free extracts of unicellular alga Chlorella pyrenoidosa using
      cisplatin- or mitomycin C-damaged plasmid DNA as the repair substrate. The algal
      extracts promoted a damage-dependent increase in 32P-dATP incorporation after
      normalization against an internal control. To identify the proteins responsible
      for NER, a biotin-labeled duplex 27 mer (2 ug) irradiated with or without UV (27
      kJ m(-2)) was immobilized on streptavidin-conjugated agarose beads and incubated
      with C. pyrenoidosa extracts (50 ug) to pull down repair proteins. The extracts
      post incubation with beads carrying unirradiated 27 mer promoted an eightfold
      increase in repair synthesis in plasmid DNA (1 ug) damaged by 16.8 pmol of
      cisplatin. The extracts obtained after affinity adsorption with UV-damaged DNA
      ligand, however, failed to repair plasmid DNA treated with cisplatin, reflecting
      that some proteins crucial to NER had been sequestered by the damaged 27 mer. A
      polypeptide approximately 70-72 kDa in molecular mass was found to bind much more
      strongly to the damaged DNA than to the control DNA after analyzing the proteins
      bound to the beads by SDS-PAGE, and this polypeptide is believed to play a role
      in NER in C. pyrenoidosa.

PMID- 10908810
TI  - Catalase gene expression in response to chronic high temperature stress in maize.
AB  - Catalase gene expression was characterized in the scutellum of maize seedlings
      grown at normal (25 degrees C) and elevated temperatures (35 and 40 degrees C).
      Chronic elevated temperatures reduce scutellar catalase activity most noticeably
      in the inbred lines W64A and R6-67, which express all three CAT isozymes (CAT-1,
      CAT-2, and CAT-3). The observed decline in catalase activity is primarily
      attributed to a decrease in the amount of CAT-2 isozyme, due to diminished levels
      of the Cat2 transcript. As CAT-2 activity levels are regulated by the trans
      acting gene locus Car1, it is possible that the Car1 gene product is inhibited at
      the elevated temperatures. In maize lines null for CAT-2 or both CAT-2 and CAT-3,
      the relative levels of Cat1 transcript, although steady throughout the 10 days
      post-imbibition scutellar profile, are slightly higher with increasing
      temperatures. This might indicate that, in thermally stressed seedlings, the
      accumulation and/or stability of Cat1 mRNA might compensate for the lack of Cat2
      transcript in a tissue where Cat2 mRNA normally accumulates during the
      developmental period examined. These observations, along with the drastic
      reduction in seed germination and seedling height at chronically elevated growth
      temperatures, suggest that developmental arrest, rather than oxidative stress,
      might be the cause for the observed results relative to Cat gene expression under
      such conditions.

PMID- 10908811
TI  - Accumulation of ammonium in rice leaves in response to excess cadmium.
AB  - The relationship between ammonium accumulation and senescence of detached rice
      leaves caused by excess cadmium (Cd) was investigated. CdCl(2) was effective in
      increasing ammonium content in detached rice leaves under both light and dark
      conditions. Both CdCl(2) and CdSO(4) induced ammonium accumulation in detached
      rice leaves, indicating that ammonium accumulation is induced by Cd ions. CdCl(2)
      promoted senescence and ammonium accumulation is not specific for the rice
      cultivar used in this study. The senescence of detached rice leaves induced by
      CdCl(2) was found to be prior to ammonium accumulation. CdCl(2) induces more
      ammonium accumulation in the dark than in the light. However, CdCl(2) treatment
      was found to be less effective in promoting senescence in the dark than in the
      light. The current results suggest that ammonium accumulation is not associated
      with the senescence of detached rice leaves induced by Cd. Evidence was presented
      to show that CdCl(2)-induced ammonium accumulation in detached rice leaves is
      attributed to a decrease in glutamine synthetase (GS) activity.

PMID- 10908812
TI  - Phenolic compounds and squalene in olive oils: the concentration and antioxidant
      potential of total phenols, simple phenols, secoiridoids, lignansand squalene.
AB  - The aim of this study was to evaluate the phenolic antioxidant and squalene
      content in a range of olive and seed oils. A mean of 290 +/- 38 (SEM) mg
      squalene/100 g was detected. However, while there was a weak significant
      difference between extra virgin (424 +/- 21 mg/kg) and refined virgin (340 +/- 31
      mg/100 g; P<0.05) olive oils, highly significant differences were evident between
      extra virgin olive oils (P<0.0001) refined virgin olive oils (P<0.0001) and seed
      oils (24 +/- 5 mg/100 g). While seed oils were devoid, on average, the olive oils
      contained 196 +/- 19 mg/kg total phenolics as judged by HPLC analysis, but the
      value for extra virgin (232 +/- 15 mg/kg) was significantly higher than that of
      refined virgin olive oil (62 +/- 12 mg/kg; P<0.0001). Appreciable quantities of
      simple phenols (hydroxytyrosol and tyrosol) were detected in olive oils, with
      significant differences between extravirgin (41.87 +/- 6.17) and refined virgin
      olive oils (4.72 +/- 215; P<0.01). The major linked phenols were secoiridoids and
      lignans. Although extra virgin contained higher concentrations of secoiridoids
      (27.72 +/- 6.84) than refined olive oils (9.30 +/- 3.81) this difference was not
      significant. On the other hand, the concentration of lignans was significantly
      higher (P<0.001) in extra virgin (41.53 +/- 3.93) compared to refined virgin
      olive oils (7.29 +/- 2.56). All classes of phenolics were shown to be potent
      antioxidants. In future epidemiologic studies, both the nature and source of
      olive oil consumed should be differentiated in ascertaining cancer risk.

PMID- 10908813
TI  - Safety evaluation of yeast glutaminase.
AB  - The consumption of soy and soy products (including soy sauce) has been increasing
      in Western countries due to purported health benefits of soy (cancer protective,
      estrogenic effects). In addition to providing soy proteins and isoflavones, soy
      sauce also functions as a flavor enhancer and is able to impart a "umami" taste.
      Glutaminases are used in the production of soy sauce and enzymatically hydrolyzed
      protein. The glutaminases described herein were produced from the cultured broth
      of Cryptococcus albidus (ATCC-20293) which is designated as CK, a mutant of C.
      albidus (ATCC-20293) which is designated as CK-D10 and the newly isolated
      Cryptococcus sp. NISL-3771 which is designated as TK. All three preparations (CK,
      CK-D10 and TK) were evaluated for pathogenicity and virulence in mice and were
      found to be non-pathogenic. The acute LD(50)s for CK in male mice was greater
      than 4.8 g/kg body weight and for female mice was greater than 6.5 g/kg body
      weight. Acute LD(50)s for CK and CK-D10 in male and female rats was greater than
      7.5 g/kg body weight, and that for TK was greater than 10 g/kg body weight.
      Subchronic (90-day) feeding studies (wherein the glutaminases were presented as
      dietary admixtures) were conducted in mice and rats. The NOAEL for CK in mice was
      7.5 g/kg body weight/day. The NOAELs in rats were as follows: for CK, 9 g/kg body
      weight/day; for CK-D10, 1.2 g/kg body weight/day, and for TK, 8 g/kg body
      weight/day. Mice received CK as a dietary admixture at levels of 0, 1.0 and 10.0%
      for 1 year. The NOAEL was 13 g/kg body weight/day. The glutaminases from C.
      albidus described herein demonstrate very low toxicity.

PMID- 10908814
TI  - Safety evaluation of a lactase enzyme preparation derived from Kluyveromyces
      lactis.
AB  - Neutralact(R), the DSM brand name of a lactase enzyme preparation, obtained from
      a homologous rDNA strain of Kluyveromyces lactis, was subjected to a series of
      toxicological tests to document the safety for use as a processing aid in the
      dairy industry. The enzyme preparation was examined for subacute oral toxicity
      and mutagenic potential. As a result of these tests, no evidence of oral
      toxicity, mutagenicity or clastogenicity was found. Administration of the lactase
      enzyme preparation at doses of 500, 3000 and 10,000 mg/kg body weight/day for 28
      days did not induce noticeable signs of toxicity. The no-observed-adverse-effect
      level (NOAEL) of the enzyme preparation in the acute toxicity study was 10,000
      mg/kg body weight/day (equivalent to 114,000 NL units/kg body weight/day). It can
      be concluded that no safety concerns were identified in the studies conducted
      with this lactase enzyme preparation derived from Kluyveromyces lactis under
      controlled fermentation conditions.

PMID- 10908815
TI  - Subacute toxicity of alpha-ergocryptine in Sprague-Dawley rats. 1: general
      toxicological effects.
AB  - The dietary subacute toxicity of the ergot alkaloid alpha-ergocryptine was
      studied in Sprague-Dawley rats. Rats were fed 0, 4, 20, 100 or 500 mg
      ergocryptine/kg diet for 28-32 days (equal to 0, 0.36, 1.7, 8.9 and 60 mg
      ergocryptine/kg body weight/day for females and 0, 0.34, 1.4, 6.6 and 44 mg
      ergocryptine/kg body weight/day for males). The present study describes the
      general toxicological effects; the effects on metabolic and hormonal parameters
      will be reported separately. Body weight, body weight gain, food intake and food
      efficiency were all decreased with a U-shaped dose-response curve, as in both
      sexes the ranking severity of effects was in the order 100-20-500 and 4 mg/kg
      diet. Other changes with a U-shaped dose-response relationship included:
      hematological parameters (decreased MCV and MCH), serum enzyme activities
      (slightly increased/decreased ALAT, ASAT, GGT), increased serum urea
      concentrations, decreased glomular filtration (creatinine and urea clearances),
      decreased absolute organ weights, increased and decreased relative organ weights,
      atrophy of thymus and in females atrophy of ovary and uterus with in the mid-dose
      groups no detectable morphological features of an oestric cycle in the uterus.
      Other parameters, including increased relative liver, heart and ovarian weights
      and necrosis of the tail, were influenced in a dose-related manner or only in the
      high dose group. The U-shaped changes for the parameters mentioned above might be
      caused by the U-shaped dose-response relationship for food intake, which may be
      explained by the dopaminergic properties of alpha-ergocryptine. It is concluded
      that in rats fed ergocryptine for 28 days the dose-effect curve is rather steep
      and that the NOAEL is 4 mg/kg diet.

PMID- 10908816
TI  - Subacute toxicity of alpha-ergocryptine in Sprague-Dawley rats. 2: metabolic and
      hormonal changes.
AB  - The present study describes the metabolic changes observed in a dietary subacute
      toxicity experiment with the ergot alkaloid alpha-ergocryptine in Sprague-Dawley
      rats. The observed effects on metabolic and hormonal parameters were described
      separately from the general toxicological effects, in view of the important role
      of dopamine agonists in metabolism (e.g. ergot alkaloids in fescue toxicosis).
      The rats were fed 0, 4, 20, 100 or 500 mg ergocryptine/kg diet for 28-32 days
      (equal to 0, 0.36, 1.7, 8.9 and 60 mg ergocryptine/kg body weight/day for females
      and 0, 0.34, 1.4, 6.6 and 44 mg ergocryptine/kg body weight/day for males). Total
      cholesterol and high-density lipoprotein (HDL)-cholesterol were decreased dose
      dependently in females but the ratio HDL-cholesterol/total cholesterol was only
      decreased at 20 mg/kg body weight. Triglycerides and glucose concentrations were
      decreased in the highest dose groups of both sexes. Serum urea concentrations
      were increased in the 20, 100 and 500 mg/kg dose groups. Insulin, glucagon and
      liver glycogen were increased in the highest dose group at the end of the study,
      when the animals were allowed to eat prior to blood sampling and necropsy.
      Prolactin, T4 and FT4 were decreased in the 20, 100 and 500 mg/kg dose groups of
      both sexes. Follicle-stimulating hormone (FSH) was decreased in the 20, 100 and
      500 mg/kg female dose groups and luteinizing hormone (LH) was increased in the
      20, 100 and 500 mg/kg male dose groups. It is postulated that the observed
      effects on food intake, metabolism (lipid and carbohydrate) and hormonal
      parameters are due to an interaction of ergocryptine with central dopaminergic
      activities, which comprise a major functional component of a central regulatory
      system for metabolism.

PMID- 10908818
TI  - A physiologically-based pharmacokinetic(PB-PK) model for ethylene dibromide:
      relevance of extrahepatic metabolism.
AB  - A physiologically-based pharmacokinetic (PB-PK) model was developed for ethylene
      dibromide (1,2-dibromoethane, EDB) for rats and humans, partly based on
      previously published in vitro data (Ploemen et al., 1997). In the present study,
      this PB-PK model has been validated for the rat. In addition, new data were used
      for the human class ThetaGST T1-1. Validation experiments are described in order
      to test the predictive value of kinetics to describe "whole-body" metabolism. For
      the validation experiments, groups of cannulated rats were dosed orally or
      intravenously with different doses of EDB. Obtained blood concentration-time
      curves of EDB for all dosing groups were compared to model predictions. It
      appeared that metabolism, which previously was assumed to be restricted to the
      liver, was underestimated. Therefore, we extended the PB-PK model to include all
      the extrahepatic organs, in which the enzymes involved in EDB metabolism have
      been detected and quantified. With this extended model, the blood concentrations
      were much more accurately described compared to the predictions of the "liver
      model". Therefore, extrahepatic metabolism was also included in the human model.
      The present study illustrates the potential application of in vitro metabolic
      parameters in risk assessment, as well as the use of PB-PK modelling as a tool to
      understand and predict in vivo data.

PMID- 10908817
TI  - Dosing via gavage or diet for reproduction studies: a pilot study using two fat
      soluble compounds-hexachlorobenzene and aroclor 1254.
AB  - The choice of a dosing route for in vivo toxicological tests is often dictated by
      practical constraints. Reproduction studies are particularly challenging in this
      regard since the determination of no-effect levels and allowable daily intakes
      from reproduction data encompasses exposure of the dam to the test xenobiotic
      prior to pregnancy, during gestation and during lactation. The fetus/infant can
      be exposed to the xenobiotic as well as the dam's metabolic products of the test
      xenobiotic during gestation and lactation. We initiated a series of two-litter,
      pilot reproduction studies with Sprague-Dawley and Fischer 344 rats to
      specifically ascertain the amount of xenobiotic and its metabolites ingested by
      the nursing neonate on lactation days 4, 7, 12, 17 and 21, when its dam received
      the xenobiotic via its diet or by gavage. The xenobiotics studied in this initial
      series of experiments were hexachlorobenzene (HCB) and Aroclor(R) 1254
      (polychlorinated biphenyls; PCBs). The dams were dosed for 28 days, mated to
      untreated males and then remated approximately 2 weeks after weaning their first
      litter to a second untreated male. Dietary levels of 10 ppm HCB or 10 ppm PCBs,
      and gavage doses of 0.9 mg HCB or 0.8 mg PCBs/kg body weight/day were chosen and
      resulted in similar doses of HCB and PCBs per unit of the body weight of the dam
      during the premating period. There were no apparent toxicological effects
      regarding the dam nor were any of the reproduction parameters (feed consumption,
      dam weight, litter size, pup weight, external anomalies and day 4 viability
      index) significantly different from control values. Following impregnation, the
      body weight of the dam increased appreciably during gestation, but its feed
      consumption increased only slightly. During lactation, the dam's feed consumption
      increased markedly while its body weight increased slightly. Consequently, when
      dams received the xenobiotic in their diet they consumed slightly less xenobiotic
      per unit of body weight during gestation when compared to the gavaged dams,
      whereas the situation was dramatically reversed during lactation. While the
      greater consumption of xenobiotic by the dietary-dosed dams during lactation did
      result in more HCB (P</=0.0001 for both litters) and PCBs/metabolites (litter
      one: P=0.05; litter two: P</=0.0001) in the suckling neonate's stomach contents
      in both generations, there was no evidence of any differences between the two
      litters when each sampling date was assessed separately, except for the day 4-HCB
      results when the litter one pups had more HCB in their stomachs (P=0.018). For
      the PCBs, the F344 neonates were found to have more PCBs in their stomachs
      (litter one P=0.0015; litter two P=0.002) than the Sprague-Dawley neonates. In
      addition, the amount of HCB, PCBs and fat in the neonates' stomachs decreased
      during lactation, as the pups age increased (P</=0.035). These preliminary
      results suggest that analogous amounts of HCB and PCBs given via diet or gavage
      may not result in similar lactational exposure by the suckling neonate.

PMID- 10908820
TI  - Eye irritation responses in rabbit and man after single applications of equal
      volumes of undiluted model liquid detergent products.
AB  - A criticism of the use of the rabbit low-volume eye test to determine eye
      irritation hazard for man is the lack of comparative data in man and rabbit with
      undiluted products. To address this, such a study has been performed in man and
      rabbit using undiluted model liquid detergents. The hypothesis tested was that
      if, under identical test conditions, the effects in the rabbit were the same or
      greater than the response in man, then it is valid to use the low-volume eye test
      to assess eye irritation hazard for man. The studies were carried out using 29
      human volunteers and 12 rabbits. The effects in the rabbit were unequivocally
      greater than the effects observed in man, but clearly less than the expected
      response from these types of product in the Draize test. The results from this
      study confirm the sensitivity of the rabbit as a test species, and support the
      use of the low-volume eye test to assess eye irritation hazard for man. Any in
      vitro/ex vivo alternative to assess eye irritation should be developed against
      the rabbit low-volume eye test or human data where available.

PMID- 10908819
TI  - Effect of saline iontophoresis on skin barrier function and cutaneous irritation
      in four ethnic groups.
AB  - The effect of saline iontophoresis on skin barrier function and irritation was
      investigated in four ethnic groups (Caucasians, Hispanics, Blacks and Asians).
      Forty healthy human volunteers were recruited according to specific entry
      criteria. Ten subjects, five males and five females, were assigned to each ethnic
      group. Skin barrier function was examined after 4 hours of saline iontophoresis
      at a current density of 0.2 mA/cm(2) on a 6.5 cm(2) area in terms of the measured
      responses: transepidermal water loss (TEWL), skin capacitance, skin temperature
      and visual scores. There were significant differences in TEWL among the ethnic
      groups prior to patch application. TEWL at baseline in ethnic groups was in the
      rank order: Caucasian>Asian>Hispanic>Black. Iontophoresis was generally well
      tolerated, and skin barrier function was not irreversibly affected by
      iontophoresis in any group. There was no significant skin temperature change,
      compared to baseline, in any ethnic groups at any observation point. Edema was
      not observed. At patch removal, the erythema score was elevated in comparison to
      baseline in all ethnic groups; erythema resolved within 24 hours. Thus, saline
      iontophoresis produced reversible changes in skin barrier function and irritation
      in healthy human subjects.

PMID- 10908822
TI  - Delirium in terminal cancer: a prospective study using daily screening, early
      diagnosis, and continuous monitoring.
AB  - A pilot prospective cohort study was conducted to determine delirium frequency
      and outcome in cancer patients consecutively hospitalized for terminal care
      (median stay: 12 days). Screening for delirium symptoms was performed daily,
      using the Confusion Rating Scale. Patients positive on screening had a diagnostic
      assessment within 24 hours using the Confusion Assessment Method. Monitoring of
      symptoms was continued until death. Eighteen (20%) of the 89 study patients were
      positive on screening at admission. Among the 71 patients free of delirium at
      admission, the incidence of confirmed delirium was 32. 8% (95% CI, 21.3-44.3%).
      Patients positive on screening received a higher mean equivalent parenteral daily
      dose of morphine than other patients (72 mg vs. 41 mg, p = 0.08). Significant
      symptom improvement occurred in 16 (50%) of the 32 delirious cases. Delirium is a
      serious and frequent complication in terminal cancer whose outcome may not be as
      poor as previously considered.

PMID- 10908821
TI  - Dietary protection by iron against clastogenic effects of short-term exposure to
      arsenic in mice in vivo.
AB  - Iron, as freshly prepared aqueous solution of ferrous sulfate, was administered
      by gavage to laboratory bred Swiss albino mice. The concentration used was 152
      mg/kg body weight (1/10 of the LD(50)). While screening for protection against
      arsenic, in one set of experiment exposure to iron was followed after 2 hr by
      gavaging with 2.5 mg/kg body weight (1/10 of the LD(50)) of arsenic as sodium
      (III) meta arsenite in distilled water. In another set, equal amounts (1:1) of
      ferrous sulfate and sodium arsenite were administered simultaneously. Control
      sets were given sodium m-arsenite alone and distilled water (vehicle). After
      exposure for 24 hr in all experiments, mice were sacrificed and chromosome
      preparations were made from bone marrow according to a colchicine-hypotonic
      fixation-air-drying-Giemsa schedule. Cytogenetic endpoints screened were
      chromosome aberrations and divisional frequencies. Sodium arsenite alone was
      highly clastogenic. Ferrous sulfate, whether given together with or before
      exposure to sodium arsenite, reduced the clastogenic effects of the latter to a
      significant extent.

PMID- 10908823
TI  - A double-blind, crossover study of controlled-release metoclopramide and placebo
      for the chronic nausea and dyspepsia of advanced cancer.
AB  - To compare a novel controlled-release formulation of metoclopramide with placebo
      in patients with cancer-associated dyspepsia syndrome, 26 adult patients with a
      >/=1 month history of cancer-associated dyspepsia syndrome were randomized to
      receive either controlled-release metoclopramide 40 mg every 12 hours or matching
      placebo for a period of 4 days. On day 5, patients crossed over to the alternate
      treatment for a further period of 4 days. Dose adjustments and rescue antiemetics
      were permitted during both phases. Nausea, anorexia, bloating, vomiting/retching,
      and drowsiness were assessed on a 100-mm VAS scale in a daily diary. On the last
      day of treatment of each phase, nausea was significantly lower in the controlled
      release metoclopramide group compared to placebo (17 +/- 12 mm versus 12 +/- 10
      mm). Nausea scores tended to increase across days during the placebo phase and to
      decrease during the controlled-release metoclopramide phase. There was a trend
      for improvement in the intensity of all symptoms on controlled-release
      metoclopramide with the exception of appetite, but this trend only reached
      statistical significance for nausea. The frequency and severity of elicited
      adverse events did not differ significantly between treatments, although
      drowsiness, dizziness, and poor sleep were somewhat higher in the placebo group.
      In no case was it necessary to discontinue controlled-release metoclopramide
      because of toxicity. These results indicate that controlled-release
      metoclopramide reduces gastrointestinal symptoms in this population of advanced
      cancer patients.

PMID- 10908824
TI  - Impact of hot flashes on quality of life among postmenopausal women being treated
      for breast cancer.
AB  - Hot flashes are among the most commonly reported symptoms among women who have
      completed treatment for breast cancer. Relatively little is known, however, about
      hot flashes among women while they are undergoing breast cancer treatment. The
      present study investigated the prevalence and severity of hot flashes of women
      during chemotherapy and radiotherapy for breast cancer. We also sought to
      identify the medical, demographic, and treatment correlates of hot flashes during
      treatment and to document the impact of hot flashes on quality of life. Seventy
      postmenopausal women with breast cancer completed a self-report questionnaire
      packet during chemotherapy and radiotherapy. Forty percent (n = 28) reported hot
      flashes during the week prior to assessment. Of the 28 women endorsing hot
      flashes, 25% (n = 7) rated them as severe, 39% (n = 11) rated them as moderate,
      and 36% (n = 10) rated them as mild. Women with hot flashes were significantly (p
      < 0.05) younger and reported significantly (p < 0.001) more fatigue, poorer sleep
      quality, and poorer physical health compared to women without hot flashes.
      Multivariate analyses revealed that, even after controlling for relevant medical,
      demographic, and treatment variables, the prevalence of hot flashes significantly
      (p < 0.05) predicted poorer sleep quality, more fatigue, and worse physical
      health. The results indicate that hot flashes are experienced by a sizable
      percentage of postmenopausal breast cancer patients as they undergo treatment.
      Hot flashes during cancer treatment appear to have a negative impact upon patient
      quality of life that may be due, in part, to fatigue and interference with sleep.
      Future research should seek to evaluate interventions to relieve hot flashes
      during breast cancer treatment as a means of improving patient quality of life.

PMID- 10908825
TI  - High level of fatigue in lymphoma patients treated with high dose therapy.
AB  - With the success of high dose therapy supported by autologous bone marrow
      transplantation (ABMT) for malignant lymphomas, medical late-effects and
      secondary effects on subjective health, like fatigue, are of concern. Fatigue is
      poorly understood and correlates have been barely addressed. Health-related
      quality of life (HRQL), fatigue, and correlates to fatigue, including
      endocrinological status and serum levels of interleukin-6, tumor necrosis factor,
      and soluble tumor necrosis factor receptors, were investigated in a cross
      sectional study of 33 lymphoma patients (median age 39 years) 4-10 years after
      ABMT. The survivors were compared to general population norms. Fatigue was highly
      prevalent, and females reported significantly more fatigue and impaired HRQL
      compared to males and the normal population. Gonadal dysfunction was found in the
      majority of the patients, but no statistically significant endocrinological or
      immunological associations with fatigue could be demonstrated. The high level of
      fatigue among female long-term survivors after ABMT may be related to the gonadal
      dysfunction, but further studies of possible mechanisms behind fatigue are
      necessary.

PMID- 10908826
TI  - A pain monitoring program for nurses: effects on nurses' pain knowledge and
      attitude.
AB  - One of the reasons for inadequate pain treatment in hospitalized patients is that
      nurses have insufficient knowledge about pain and pain management. To address
      this problem, a Pain Monitoring Program (PMP) for nurses was developed,
      implemented, and evaluated. The PMP consisted of two components: educating nurses
      about pain, pain assessment, and pain management, and implementing daily pain
      assessment by means of a numeric rating scale. The effects of the PMP were
      measured in a one-group pretest-post-test design. The results show that nurses
      have knowledge deficits and prejudices with regard to pain and pain management.
      Age and additional pain courses in pain partly predict nurses' pain knowledge.
      After nurses were educated, the average score on the Pain Knowledge Questionnaire
      increased from 69.1% (SD = 13.2) at pretest to 75.8% (SD = 11.5) at post-test (P
      < 0.001). Nurses' attitudes changed with regard to their level of knowledge and
      skills in relieving pain, willingness to assess pain on a daily basis, and
      attention to patients' pain complaints. It can be concluded that the PMP is
      effective in improving nurses' knowledge of pain management and focusing nurses'
      attention to patients' pain complaints.

PMID- 10908827
TI  - Conscious sedation with remifentanil during painful medical procedures.
AB  - Remifentanil, a recently introduced ultra-short acting opioid, was used as a
      component of a conscious sedation technique in 30 patients for 40 painful medical
      procedures. In 31 of these procedures, remifentanil provided sufficient
      analgesia. However, 25 of those 31 patients developed apnea that required
      constant verbal stimulation at doses equal to or less than the dose required for
      analgesia. Ten of these apneic patients developed hypoxemia (oxyhemoglobin
      saturation less than 90%). Nine patients required abandonment of remifentanil and
      addition of either ketamine or propofol to achieve an analgesic state without
      respiratory depression. Although discharge times with remifentanil were
      considerably shorter, most patients, parents, and practitioners were not
      satisfied with the technique because of the prolonged time to reach an analgesic
      state, and their fear of persistent apnea. Therefore, remifentanil is generally
      not a useful agent as part of a conscious sedation technique during brief painful
      procedures. Although discharge times are rapid, it is accompanied by a high
      incidence of life-threatening respiratory depression at subtherapeutic levels.

PMID- 10908828
TI  - Case presentation: a case of euthanasia, the Northern Territory, Australia.

PMID- 10908829
TI  - The challenge of informed consent.

PMID- 10908830
TI  - Commentary: assessment of clinical depression in patients who request physician
      assisted death.

PMID- 10908831
TI  - Periconceptional use of folic acid to reduce the rates of neural tube defects: is
      it working?

PMID- 10908832
TI  - Prioritization of NTP reproductive toxicants for field studies.
AB  - Population studies that evaluate human reproductive impairment are time
      consuming, expensive, logistically difficult, and with limited resources must be
      prioritized to effectively prevent the adverse health effects in humans.
      Interactions among health scientists, unions, and industry can serve to identify
      populations exposed to potential hazards and develop strategies to evaluate and
      apply appropriate controls. This report describes a systematic method for
      prioritizing chemicals that may need human reproductive health field studies.
      Rodent reproductive toxicants identified from the National Toxicology Program
      (NTP) Reproductive Assessment by Continuous Breeding (RACB) protocol were
      prioritized on the basis of potency of toxic effect and population at risk. This
      model for prioritization links NTP findings with data from the National
      Occupational Exposure Survey (NOES) and the Hazardous Substance Data Base (HSDB)
      or the High Production Volume Chemical Database (HPVC) to prioritize chemicals
      for their potential impact on worker populations. The chemicals with the highest
      priority for field study were: dibutyl phthalate, boric acid, tricresyl
      phosphate, and N, N-dimethylformamide.

PMID- 10908833
TI  - Drinking water chlorination and delivery outcome-a registry-based study in
      Sweden.
AB  - By using the Swedish Medical Birth Registry and official data on drinking water
      chlorination, three cohorts were identified and compared: women who lived in
      areas where drinking water was disinfected with chlorine dioxide, women who lived
      in areas that used sodium hypochlorite disinfection, and women who lived in areas
      where there was no chlorination of the drinking water. There was a statistically
      significant increase in short gestational duration and low birth weight and
      especially in short body length and very small head circumference in areas using
      sodium hypochlorite, but no significant effects on these variables were found in
      areas using chlorine dioxide. No effects on congenital malformations, childhood
      cancer, infant mortality, low Apgar score, neonatal jaundice, or neonatal
      hypothyroidism were associated with either of the two drinking water chlorination
      methods. Because the exposure information in this study was based on the
      chlorination method and not the amount of byproducts in the water, the general
      lack of significant effects could be due to a low concentration of such
      byproducts.

PMID- 10908834
TI  - Vitamin A teratogenicity and risk assessment in the macaque retinoid model.
AB  - Studies were performed in the cynomolgus monkey (Macaca fascicularis) to provide
      risk assessment information on safe dose levels of Vitamin A during human
      pregnancy. Vitamin A palmitate was orally administered at 7500 IU/kg (2.25 mg/kg)
      to 80 000 IU/kg (24 mg/kg) body weight during early pregnancy (gestation day [GD]
      16-27). The results indicated a dose-related increase in exposure (AUC) to
      retinyl esters and retinoic acids (RA) (all-trans-RA, all-trans-4-oxo-RA, 13-cis
      RA, 13-cis-4-oxo-RA). There was also a dose-related increase in abortion and
      malformation that affected typical retinoid target tissues in the embryo,
      including the craniofacial region, heart, and thymus. The NOAEL and LOAEL for
      structural malformations were 7500 IU/kg and 20 000 IU/kg (6 mg/kg),
      respectively. A companion study involving oral administration of 13-cis-RA during
      the same gestational period established the NOAEL for malformations at 0.5
      mg/kg/day, which is close to the human therapeutic dose range (0.5 to 1.5
      mg/kg/day) associated with retinoid embryopathy. Based on the known similarities
      in teratogenic susceptibility to 13-cis-RA, the monkey NOAEL for Vitamin A (7500
      IU/kg) was used to estimate safe levels of this nutrient in humans applying a
      safety factor of 10. This approach yielded safe levels of Vitamin A during human
      pregnancy in the range of approximately 25 000 to 37 000 IU/day.

PMID- 10908835
TI  - Fertility of male workers of the italian mint.
AB  - Fertility among workers exposed to metal fumes and solvents in the Italian mint
      (stampers, founders, and other technical workers) was compared to the
      reproductive experience of the administrative staff. Data on the reproductive
      history and time to pregnancy were collected by interview. For workers with
      children, data on the time to pregnancy (TTP) for the first pregnancy was
      assessed in relation to occupational risk factors. The groups with the highest
      prevalence of pregnancy delay beyond 6 months were stampers (21%) and those
      exposed to solvents (21.5%). Logistic regression did not show a significant
      association of these job exposures with pregnancy delay, but the power of the
      study to show an important difference was low. The data are not inconsistent with
      the hypothesis that male exposure to solvents and metal fumes is associated with
      an increase in the TTP.

PMID- 10908836
TI  - Increased micronuclei frequencies in couples with reproductive failure.
AB  - A higher incidence of chromosomal instability in the infertile population is
      widely recognized. An increased level of micronuclei has been shown to be a
      marker of chromosome damage. Therefore, micronuclei frequencies were assessed in
      cytokinesis-blocked lymphocytes of 130 patients (65 couples) with idiopathic
      infertility or with two or more spontaneous abortions, and 30 healthy fertile
      donors (15 couples). The frequency of micronucleated cells in the cohort with
      reproductive failure and healthy controls averaged 14.95+/-6.04 per 1000 and
      10.60 +/-2.57 per 1000 (P<0.0001), respectively. When micronuclei frequency sums
      in particular couples (male + female) were analyzed in the same order, identical
      statistical significance was reached (P<0.0001). We found no effect of age or sex
      on micronuclei frequency. In summary, the cytokinesis-blocked micronuclei assay
      revealed increased micronucleus frequency in couples with infertility or two or
      more spontaneous abortions, suggesting a possible role of chromosomal instability
      in reproductive failure.

PMID- 10908837
TI  - Assessment in rats of the reproductive toxicity of gasoline from a gasoline vapor
      recovery unit.
AB  - Gasoline (CAS 86290-81-5) is one of the world's largest volume commercial
      products. Although numerous toxicology studies have been conducted, the potential
      for reproductive toxicity has not been directly assessed. Accordingly, a two
      generation reproductive toxicity study in rats was conducted to provide base data
      for hazard assessment and risk characterization. The test material, vapor
      recovery unit gasoline (68514-15-8), is the volatile fraction of formulated
      gasoline and the material with which humans are most likely to come in contact.
      The study was of standard design. Exposures were by inhalation at target
      concentrations of 5000, 10 000, and 20 000 mg/m(3). The highest exposure
      concentration was approximately 50% of the lower explosive limit and several
      orders of magnitude above anticipated exposure during refueling. There were no
      treatment-related clinical or systemic effects in the parental animals, and no
      microscopic changes other than hyaline droplet nephropathy in the kidneys of the
      male rats. None of the reproductive parameters were affected, and there were no
      deleterious effects on offspring survival and growth. The potential for endocrine
      modulation was also assessed by analysis of sperm count and quality as well as
      time to onset of developmental landmarks. No toxicologically important
      differences were found. Therefore, the NOAEL for reproductive toxicity in this
      study was > or =20 000 mg/m(3). The only systemic effects, in the kidneys of the
      male rats, were consistent with an alpha-2 u-globulin-mediated process. This is a
      male rat-specific effect and not relevant to human health risk assessment.

PMID- 10908838
TI  - Hepatic alpha(2u)-globulin mRNA levels and diethylstilbestrol-associated
      testicular atrophy in rats.
AB  - Biosynthesis of alpha(2u)-Globulin (alpha(2u)-g) is under multihormonal
      regulation. In this study, we investigated histopathologic changes in the testis
      and hepatic alpha(2u)-g messenger ribonucleic acid (mRNA) levels in male rats
      after administration of the potent estrogen diethylstilbestrol (DES) at 0. 01,
      0.1, or 1 mg/kg/day by gavage for 14 days. DES treatment decreased hepatic
      alpha(2u)-g mRNA levels in a dose-dependent manner accompanied by atrophic
      histopathologic changes in the testis. In addition, alpha(2u)-g mRNA levels were
      lowest in animals with the most marked testicular changes. Hepatic alpha(2u)-g
      mRNA may be a useful biomarker for the evaluation of endocrine disruption in male
      rats.

PMID- 10908840
TI  - Hierarchization of animal teratology findings for improving the human risk
      evaluation of drugs.
AB  - The risk assessment of drugs in pregnancy can be improved through better
      knowledge and interpretation of significant experimental findings. Embryo-fetal
      effects can be considered as the endpoint of importance, after excluding that
      their occurrence is related to maternal toxicity. If embryo-fetal toxic effects
      occur in the presence of maternal toxicity, the dam influence should be clearly
      assessed, and can be taken into account in the determination of a safety margin.
      A determination of the lowest developmental toxic dose, if any, apart from any
      maternal toxicity, should be made. With positive animal developmental findings,
      interpretation should take into account various parameters including the
      incidence and the severity of the embryo-fetal insult, interspecies
      reproducibility, the level of exposure, metabolic pathways, and the results of
      possible mechanistic investigations. Hierarchization of the experimental findings
      should take into account all these parameters together to provide support for the
      risk assessment in humans.

PMID- 10908839
TI  - Effect of different sampling designs on outcome of endocrine disruptor studies.
AB  - In this article, we demonstrate how sampling strategy can influence the outcome
      of endocrine disruptor studies. In a study of the weak xenoestrogen bisphenol A
      (BPA), possible treatment-related effects on ventral prostate (VP) fresh weight
      were found in rat offspring at 6 months of age when only one or two male pups
      were randomly selected from each litter. In subsequent BPA and di-n-butyl
      phthalate studies, large intralitter variability of this specific end point was
      apparent when the VP weights from entire litter complements were examined. We
      modeled the effects of sampling 1, 2, or 3 pups from each litter using the full
      litter complement data. When one pup was randomly selected, a substantial
      percentage of incorrect conclusions about the presence or absence of treatment
      effects occurred. These statistical modeling analyses raise significant concern
      about the selection of one pup per litter for highly variable end points.

PMID- 10908841
TI  - Advanced bladder and urothelial cancers.
AB  - After more than 40 years of use, cytotoxic chemotherapy has an evolving role in
      the management of advanced bladder cancer. Standard single-agent regimens, such
      as methotrexate, doxorubicin, vinblastine and cisplatin, have produced objective
      response rates of 15-25%, and combination chemotherapy causes objective
      regression in 50-75% of cases. Novel compounds such as ifosfamide, the taxanes
      and gemcitabine are now being incorporated into combination regimens, having
      shown activity in this disease, both in previously treated and untreated cases.
      The phenomenon of stage migration, with increased precision of imaging, leads to
      the inclusion of different populations of patients with advanced disease into
      protocols of assessment of chemotherapy. This may cause an artifact of improved
      outcome, when in fact the higher response rates and longer survival figures may
      reflect a reduced burden of disease and case selection. It is thus essential to
      validate novel approaches in well structured, randomised clinical trials that
      compare new strategies against established standard protocols. Historical
      comparisons serve only to confuse the issue by introducing errors from case
      selection bias, stage migration and differences in duration of follow-up and
      supportive technologies.

PMID- 10908842
TI  - Paclitaxel and carboplatin in bladder cancer: recent developments.
AB  - Paclitaxel demonstrates significant single-agent activity in advanced urothelial
      carcinoma. Paclitaxel/carboplatin is an active and tolerable outpatient
      chemotherapy treatment regimen for these patients. This regimen has been studied
      in several phase II trials with response rates ranging from 14 to 65%.
      Paclitaxel/carboplatin may be considered in patients with advanced urothelial
      cancer and renal insufficiency, and a recent Eastern Cooperative Oncology Group
      (ECOG) phase II trial investigates this regimen specifically in this patient
      population. Ongoing ECOG trials are comparing paclitaxel/carboplatin with M-VAC
      (methotrexate, vinblastine, doxorubicin, cisplatin) in both the advanced disease
      and adjuvant settings.

PMID- 10908843
TI  - Gemcitabine and cisplatin in locally advanced and/or metastatic bladder cancer.
AB  - Although transitional cell carcinoma of the urothelium is chemosensitive, long
      term disease-free survival is low. Accordingly, interest has focused on combining
      classically active agents like cisplatin with promising new drugs. Gemcitabine
      has evoked interest not only because of its intrinsic activity against this
      cancer, but also because of its effect of inhibiting repair of DNA that has been
      damaged by drugs like cisplatin. Four phase II studies have assessed the effect
      of a gemcitabine-cisplatin combination on advanced or metastatic bladder cancer.
      All the studies employed a gemcitabine dose of 1000 mg/m(2) given on days 1, 8
      and 15, whereas the cisplatin dose and schedule varied, with total doses ranging
      from 70 to 105 mg/m(2). Overall response rates in these studies ranged from 42 to
      66%, with complete responses from 15 to 28%. Toxicities, which were primarily
      haematological, were generally manageable. This promising two-drug combination
      has been compared with the standard MVAC regimen (methotrexate, vinblastine,
      doxorubicin, and cisplatin) in a randomised phase III trial and the results are
      eagerly anticipated.

PMID- 10908844
TI  - Gemcitabine/paclitaxel-based three-drug regimens in advanced urothelial cancer.
AB  - Transitional cell carcinoma (TCC) of the urothelium is a highly chemosensitive
      tumour. Combination chemotherapy can provide both palliation and a modest
      survival advantage in patients with advanced disease. At present, the combination
      of cisplatin, methotrexate, doxorubicin and vinblastine (M-VAC) is the most
      widely used for advanced TCC with an overall response rate of 40-72% in phase II,
      and 35-45% in phase III studies, and a median survival of approximately 12
      months. These modest results and the unsuccessful attempts to increase efficacy
      with dose intensive M-VAC schedules have prompted the identification of new
      active agents in TCC, such as the taxanes and gemcitabine. The overall response
      rates for two-drug regimens of cisplatin-paclitaxel, carboplatin-paclitaxel and
      cisplatin-gemcitabine range from 63 to 72%, 14 to 65% and 42 to 66%,
      respectively. The overall response rates for platinum-paclitaxel-gemcitabine
      three-drug regimens range from 58 to 80%. The potential clinical benefit of these
      new three-drug combinations in the treatment of TCC needs to be tested in future
      phase III studies.

PMID- 10908845
TI  - Exploring sequenced chemotherapy regimens in the treatment of transitional cell
      carcinoma of the urothelial tract.
AB  - This phase I trial evaluated the two-drug regimen doxorubicin and gemcitabine
      (AG) every other week for six cycles followed by ifosfamide, paclitaxel and
      cisplatin (ITP) every 3 weeks for four cycles in patients with transitional cell
      carcinoma of the urothelial tract. 15 patients were treated at five AG dose
      levels ranging up to doxorubicin 50 mg/m(2) and gemcitabine 2000 mg/m(2). The
      dose and schedule of ITP were constant at ifosfamide 1500 mg/m(2) on days 1-3 and
      paclitaxel 200 mg/m(2) and cisplatin 70 mg/m(2) on day 1. Granulocyte colony
      stimulating factor was self-administered between all cycles of therapy. The trial
      determined that AG given at alternating weeks at doses of doxorubicin 50 mg/m(2)
      and gemcitabine 2000 mg/m(2) was feasible. After completion of the AG-ITP
      sequence, 9 of 14 (64%) evaluable patients had a major response (3 complete
      responses and 6 partial responses). Phase II investigation at the highest dose
      level is ongoing.

PMID- 10908846
TI  - Gemcitabine and paclitaxel combination therapy in transitional cell carcinoma of
      the urothelium.
AB  - Transitional cell carcinoma (TCC) of the urothelium is considered a
      chemosensitive malignancy; however, few patients receiving standard therapies
      achieve long-term disease control. Thus, new treatment approaches using more
      effective and less toxic agents are needed to improve prognosis in these
      patients. Two new agents currently being studied are gemcitabine and the taxanes;
      both of which have produced overall response rates ranging from 22.5 to 28%
      (gemcitabine), and 7-56% (paclitaxel) when used as single agents in this disease.
      Both agents have been well tolerated. Results of two phase II studies of
      gemcitabine combined with paclitaxel have been published. In one, 60% (15/25) of
      evaluable patients with advanced stage IV TCC responded; in the other, 53% (8/15)
      of patients with advanced and/or metastatic TCC responded. Several trials
      evaluating different dosing regimens of gemcitabine plus paclitaxel or docetaxel
      are ongoing or planned.

PMID- 10908847
TI  - A phase II study of gemcitabine plus cisplatin chemotherapy in advanced
      bilharzial bladder carcinoma.
AB  - Bilharzial bladder cancer represents a distinct clinicopathological entity. To
      investigate whether gemcitabine-cisplatin is also active against bladder cancer
      of bilharzial origin, we performed a phase II study of previously untreated
      patients with stage III/IV disease. Standard eligibility criteria were used.
      Patients received gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 and cisplatin
      (70 mg/m(2)) on day 2 of every 28-day cycle. The 32 males and 5 females had a
      median age of 59 years (range: 29-81 years). Of 33 evaluable patients, 8 (24%)
      achieved complete responses, and 10 (30%) partial responses, for an overall
      response rate of 55%. 3 patients had minor responses. Responses were observed at
      all disease sites including lung and liver lesions. Myelosuppression was
      significant but manageable. Non-haematological toxicity was limited mainly to
      nausea and vomiting and raised liver enzymes. Thus, these data suggest that
      gemcitabine plus cisplatin induces high response rates in patients with
      bilharzial bladder cancer with a moderate toxicity profile.

PMID- 10908848
TI  - Reproductive characteristics and strategies of reducing-system bivalves.
AB  - The reproductive biology of Type 3 reducing-system bivalves (those whose pallial
      cavity is irrigated with water rich in reducing substances) is reviewed, with
      respect to size-at-maturity, sexuality, reproductive cycle, gamete size, symbiont
      transmission, and larval development/dispersal strategies. The pattern which
      emerges from the fragmentary data is that these organisms present reproductive
      particularities associated with their habitat, and with their degree of reliance
      on bacterial endosymbionts. A partial exception to this pattern is the genus
      Bathymodiolus, which also presents fewer trophic adaptations to the reducing
      environment, suggesting a bivalent adaptive strategy. A more complete
      understanding of the reproductive biology of Type 3 bivalves requires much more
      data, which may not be feasible for some aspects in the deep-sea species.

PMID- 10908849
TI  - Cellular and molecular constituents of olfactory sensation in vertebrates.
AB  - Since the discovery of odorant-activated adenylate cyclase in the olfactory
      receptor cilia, research into the olfactory perception of vertebrates has rapidly
      expanded. Recent studies have shown how the odor discrimination starts at the
      receptor level: each of 700-1000 types of the olfactory neurons in the neural
      olfactory epithelium contains a single type of odor receptor protein. Although
      the receptors have relatively low specific affinities for odorants, excitation of
      different types of receptors forms an excitation pattern specific to each odorant
      in the glomerular layer of the olfactory bulb. It was demonstrated that adenosine
      3',5'-cyclic monophosphate (cAMP) is very likely the sole second messenger for
      olfactory transduction. It was also demonstrated that the affinity of the cyclic
      nucleotide-gated channel for cAMP regulated by Ca(2+)/calmodulin is solely
      responsible for the adaptation of the cell. However, many other regulatory
      components were found in the transduction cascade. Regulated by Ca(2+) and/or the
      protein-phosphorylation, many of them may serve for the adaptation of the cell,
      probably on a longer time scale. It may be important to consider the
      resensitization as a part of this adaptation, as well as to collect kinetic data
      of each reaction to gain further insight into the olfactory mechanism.

PMID- 10908850
TI  - Symbiosis-enhanced gene expression in cnidarian-algal associations: cloning and
      characterization of a cDNA, sym32, encoding a possible cell adhesion protein.
AB  - Mutualistic endosymbioses between two partners are complex associations that are
      regulated by the genetic interactions of the partners. One important marine
      symbiosis is that between various cnidarians, such as corals and anemones, and
      their photosynthetic algal symbionts. We have been interested in characterizing
      cnidarian host genes that are expressed as a function of the symbiotic state,
      using the temperate sea anemone Anthopleura elegantissima as a model. In this
      study, we report on symbiosis-enhanced expression and synthesis of sym32 in
      anemones. We characterized the full-length sym32 cDNA, obtained by RT-PCR, and
      demonstrated, by semi-quantitative RT-PCR, that sym32 transcript was much more
      abundant in symbiotic than in non-symbiotic host anemone RNA. Further, using
      immunoblots, we determined that an antibody made to a sym32 fusion protein
      labeled a 32 kD band much more strongly in symbiotic compared to non-symbiotic
      anemone protein homogenates. Databank searches revealed that the sym32 deduced
      amino acid sequence shares significant homology with the fasciclin I (Fas I)
      family of homophilic cell adhesion proteins, present in a variety of organisms
      ranging from bacteria to humans. This strong homology with the Fas I family
      suggests that sym32 is involved in regulation of the symbiosis by mediating cell
      cell interactions.

PMID- 10908851
TI  - Rapid GLUT-1 mediated glucose transport in erythrocytes from the grey-headed
      fruit bat (Pteropus poliocephalus).
AB  - D-Glucose entry into erythrocytes from adult grey-headed flying fox fruit bats
      (Pteropus poliocephalus) was rapid and showed saturation at high substrate
      concentrations. Kinetic parameters were estimated from the concentration
      dependence of initial rates of zero-trans D-glucose entry at 5.5 degrees C as
      Michaelis constant (K(m)) 1. 64+/-0.56 mM, and maximal velocity (V(max)) 1162+/
      152 micromol.l. cell water(-1).min(-1). D-Glucose entry was inhibited by
      cytochalasin B; mass law analysis of D-glucose-displaceable cytochalasin B
      binding gave values of K(d) 37.1+/-5.0 nM and B(max) 361.2+/-9.1 pmol/mg membrane
      protein. Entry of 2-deoxy-D-glucose, and 3-O-methyl-D-glucose, into P.
      poliocephalus red cells was rapid, entry of D-fructose was very slow. Glucose
      transporter polypeptides were identified on immunoblots as a band M(r) 47000
      54000 and their identity confirmed by D-glucose-sensitive photolabeling of
      membranes with [3H]-cytochalasin B. Peptide-N-glycanase F digestion of both human
      and bat erythrocyte membranes generated GLUT-1-derived bands M(r) 37000. Trypsin
      digestion of human and fruit bat erythrocyte membranes generated fragmentation
      patterns consistent with similar GLUT-1 polypeptide structures in both species.
      Erythrocytes from adult Australian ghost bats (Macroderma gigas), a carnivorous
      microchiropteran bat, also expressed high levels of GLUT-1.

PMID- 10908852
TI  - Bimodal respiration and ventilatory behavior in two species of central American
      turtles: effects of forced submergence.
AB  - Respiratory gas exchange in both air and water was measured at rest and during
      recovery from forced submergence in the giant Mexican musk turtle (Staurotypus
      triporcatus) and the white-lipped mud turtle (Kinosternon leucostomum). Diving
      and ventilatory behavior were also measured in unrestrained animals of each
      species. Despite large differences in cutaneous surface area, both species
      exhibited an aquatic V(O(2)) and V(CO(2)) of approximately 16 and 45%,
      respectively, with the remainder explained by aerial gas exchange. Aquatic
      V(O(2)) and V(CO(2)) did not significantly change during forced submergence or
      during the recovery period. Aerial V(O(2)) and V(CO(2)), however, profoundly
      increased after forced submergence in both species and were not significantly
      different from resting values until approximately 60 min following the treatment.
      At rest, K. leucostomum took significantly more breaths per breathing bout than
      S. triporcatus. This inherent ventilation pattern in each species remained
      unaltered following forced submergence. Cutaneous surface area, therefore,
      remains a minor component for these two species which rely heavily on pulmonary
      gas exchange to recover from forced submergence.

PMID- 10908853
TI  - Electrophysiological responses of crayfish oocytes to biogenic amines.
AB  - Intracellular recordings were made from immature, growing oocytes of the crayfish
      Pacifastacus leniusciulus. Oocytes had a relatively negative resting potential of
      -74.7+/-2.2 mV (n=26; range -53 to -90) and a mean input resistance of 0.86+/
      0.19 MOmega (n=22; range 0.17-3.3). Octopamine induced a long-lasting response
      involving biphasic changes in input resistance, together with bi- or multiphasic
      changes in membrane potential. The resistance-decreasing phase involved (in
      different oocytes) membrane hyperpolarization, depolarization or both. The
      resistance-increasing phase was usually a depolarization. The hyperpolarizing
      form of the resistance-decreasing response, and the depolarizing resistance
      increasing response reversed in polarity at membrane potentials of (respectively)
      -90 and -92 mV, suggesting increases and decreases in K(+) conductance underly
      the biphasic changes in input resistance. The threshold concentration for the
      response was remarkably low (>10(-12) M) and showed little or no dose-dependence
      over the concentration range 10(-12)-10(-6) M. Similar responses were evoked by
      dopamine and serotonin (at 10(-9) M), although a higher proportion of oocytes
      responded to octopamine and/or dopamine than to serotonin.

PMID- 10908855
TI  - Gastrointestinal transit times in young and old cats.
AB  - Ageing results in a decrease in apparent nutrient digestibility in the
      gastrointestinal (GI) tract. The aim of this study was to investigate whether the
      rate of gastric emptying or total GI transit times differed between young (3.0+/
      0.9 years) and senior (11.6+/-1. 4 years) cats. Gastric emptying rates were
      measured using [1-(13)C]octanoic acid and total transit times with chromium
      oxide. No significant differences (P>0.05) were observed in either the rate of
      gastric emptying or total transit time between young and senior cats although
      senior cats exhibited a larger variability in total transit time compared to the
      younger cats (35.71+/-14.06 and 26. 46+/-5.80 h, respectively). The results of
      this study indicate that the observed reduction in nutrient digestibility in
      ageing cats is not due to alterations in the rate of passage of digesta through
      the GI tract.

PMID- 10908854
TI  - Effects of cholecystokinin on acid formation in glands and cells isolated from
      rabbit and rat gastric mucosa.
AB  - Isolated gastric glands and isolated cells prepared from rabbit and rat were
      studied to analyse the influence of cholecystokinin octapeptide (CCK 8) on
      histamine stimulated parietal cell acid formation as assessed by [14C]aminopyrine
      sequestered in acid tissue compartments. In rabbit gastric glands, CCK 8 evoked
      32+/-6% (P<0. 01) inhibition of histamine stimulated acid formation, whereas in
      glands prepared from rat no inhibition was recorded. Instead, CCK 8 seemed to
      induce a variable increase of the histamine stimulation in rat gastric glands as
      the aminopyrine accumulation was increased by 110+/-46% (P<0.1). Further studies
      on cell preparations derived from rabbit gastric mucosa revealed dual properties
      of CCK 8, eliciting either inhibition or stimulation of the parietal cell
      depending on the presence of endocrine cells. The results show that paracrine
      communication may be effective in glandular preparations, but seems to vary
      depending on species.

PMID- 10908856
TI  - Metabolism in two breeds of geese with moderate or large overfeeding induced
      liver-steatosis.
AB  - Biochemical mechanisms which may control fat deposition in liver and/or
      peripheral tissues have been studied in Poland and Landes geese. Post-prandial
      plasma substrates and post-heparin lipoprotein-lipase (LPL) activity were
      measured in 10-week-old animals. At 23 weeks of age, geese were overfed for 14
      days then slaughtered. Hepatic steatosis was more important in Landes geese,
      while muscle and subcutaneous adipose tissue were less developed. In this breed,
      fatty liver weight negatively scaled to LPL activity, suggesting that a low LPL
      activity is a limiting factor of peripheral fat deposition. Consequently, non
      catabolized VLDL may return to liver and increase hepatic steatosis. In Poland
      geese, such a mechanism does not exist. On the other hand, fatty liver weight was
      positively correlated to very low density lipoproteins (VLDL) and
      triacylglycerols measured in overfed Poland geese, suggesting that lipids
      synthetized by liver are better transferred from liver to extrahepatic tissues.
      Kinetics of post-prandial plasma glucose, triacylglycerols, phospholipids and
      uric acid were similar in the two breeds. However, the marked decrease in post
      prandial plasma glycerol in Poland geese suggests that an extrahepatic tissue
      lipolysis inhibition could contribute to the higher peripheral fattening in
      overfed Poland geese and could be a limiting factor of hepatic steatosis in this
      breed.

PMID- 10908857
TI  - Comparison of alpha-amylase and protease activities of a zoophytophagous and two
      phytozoophagous Heteroptera.
AB  - To better understand the nature of facultative phytophagy in the zoophytophagous
      Geocoris punctipes (Say), and facultative zoophagy in phytozoophagous Lygus
      hesperus (Knight) and Lygus lineolaris (Palisot de Beauvois), we compared the
      activities of both the starch digesting enzyme alpha-amylase and of general
      proteases in these species. The alpha-amylases and proteases were demonstrated in
      L. hesperus, L. lineolaris and G. punctipes. The presence of alpha-amylase in the
      salivary gland complexes of G. punctipes indicates a disposition of this species
      toward utilization of nutrients that can be derived only from plants, either
      directly from ingestion of plant macromolecules or from second-hand ingestion of
      plant material from the digestive system of their prey. The alpha-amylase
      activity in G. punctipes was much less than those of phytozoophagous L. hesperus
      and L. lineolaris. The relative importance of amylolytic activity and proteolytic
      activity is also discussed.

PMID- 10908858
TI  - Liver total lipids and fatty acid composition of shot red and fallow deer males
      in various reproduction periods.
AB  - In this study total lipid (TL) content and the fatty acid composition changes in
      the liver of red deer stags (n=35) and fallow deer bucks (n=19) were examined at
      various reproductive stages. Samples were taken from mature red deer stags in the
      rut (September), in the post-rut (October), at the end of the rut (November) and
      after sexual activity had ceased (January). Sampling from mature fallow bucks was
      performed in the pre-rut (early October), in the rut (November) and after the
      reproduction period (January). The results obtained indicated significant
      (P<0.001) fatty degeneration of the liver in the males at the rutting season. At
      that time the TL concentration (x+/-S.D. in wet weight) was 156+/-40 g/kg in the
      red deer stags and 405+/-46 g/kg in the fallow bucks. Subsequent to the rutting
      season this value decreased to 47+/-15 g/kg by November in the red deer stags and
      to 51+/-3 g/kg by January in the fallow bucks. Significant changes were also
      observed in the fatty acid composition of the liver lipids, determined by gas
      chromatography. Liver samples collected during the rutting season from both red
      deer stags and fallow bucks showed higher (P<0.001) total proportions of
      monounsaturated fatty acids and lower (P<0.001) weight percentages of
      polyunsaturated fatty acids than those taken in January. In comparison with
      January the liver samples taken in September from red deer stags showed
      significantly higher (P<0.001) proportions of fatty acids C14:0, C15:0 and
      C:16:1, and significantly lower (P<0. 001) proportions of C18:0, C20:4 (n-6) and
      C22:5 (n-3). The proportions of C14:0, C15:1, C17:1 and C18:3 (n-3) in the liver
      samples taken in November from fallow bucks were higher (P<0.001), while the
      proportions of C18:0 and C20:4 (n-6) were lower (P<0.001) than those measured
      prior to rutting (in October) or after the rut (in January).

PMID- 10908859
TI  - Glutamine metabolism in endothelial cells: ornithine synthesis from glutamine via
      pyrroline-5-carboxylate synthase.
AB  - L-Glutamine (the most abundant free amino acid in plasma and the body) is a
      potent inhibitor of endothelial NO synthesis. However, little is known about
      glutamine metabolism in endothelial cells (EC). As an initial step toward
      understanding the role of glutamine in endothelial physiology, the present study
      was conducted to quantify glutamine catabolism in microvascular, aortic and
      venous EC. For metabolic studies, EC were incubated for 1 h in Krebs bicarbonate
      buffer containing 5 mM glucose and 0.5-4 mM L-[U-(14)C]-glutamine. For
      enzymological studies, cell extracts and mitochondrial fractions were prepared to
      determine the activities of glutamine-degrading enzymes. Our results reveal
      extensive hydrolysis of glutamine to glutamate and ammonia in a concentration
      dependent manner via phosphate-dependent glutaminase in all EC studied. In
      addition, both metabolic and enzymological evidence indicate a novel pathway for
      endothelial synthesis of ornithine from glutamine via pyrroline-5-carboxylate
      synthase. This new knowledge of glutamine metabolism may pave a new path for
      understanding the physiological role of glutamine in vascular function.

PMID- 10908860
TI  - Juvenile pallid (Scaphirhynchus albus) and hybrid pallidxshovelnose (S.
      albusxplatorynchus) sturgeons exhibit low physiological responses to acute
      handling and severe confinement.
AB  - Following a 7.5-h transport haul, juvenile pallid sturgeon (Scaphirhynchus albus)
      showed a small but significant increase in plasma cortisol to 4.7 ng ml(-1) but
      similar increases did not occur after fish were handled in a net held in the air
      for 30 s. Subsequent experiments on yearling pallid sturgeon and hybrid
      pallidxshovelnose (S. albusxplatorynchus) sturgeon using the same 30-s handling
      stressor failed to evoke increases in plasma cortisol, lactate or glucose. Plasma
      cortisol increased significantly from about 2 to 13-14 ng ml(-1) in both pallid
      and hybrid sturgeon during a 6-h severe confinement stressor with handling.
      Plasma cortisol in 2-year-old pallid sturgeon subjected to the same stressor
      demonstrated a linear pattern of increase during the initial 1 h. Plasma lactate
      increased from 1.11 to about 2.11 mmol l(-1) in hybrid sturgeon during the first
      hour of severe confinement but did not change throughout the entire confinement
      period in pallid sturgeon. A significant increase in plasma cortisol to 5.4 ng
      ml(-1) in 2-year-old pallid sturgeon 1 h after being subjected to 30 s handling
      at 19:00 h but not at 07:00 or 13:00 h suggests that a small diurnal variation in
      their stress response may exist. Although both pallid and hybrid sturgeons were
      responsive to stress, they exhibited very low physiological responses compared
      with those following equivalent stressors in most teleostean fishes or another
      chondrostean, the paddlefish (Polyodon spathula). Reasons for the apparent low
      responses to handling and confinement in scaphirhynchid sturgeons are not known
      but may relate to their evolutionary history, neuroendocrine mechanisms involved
      in their corticosteroid responses, or anatomy of their interrenal tissue
      structure.

PMID- 10908861
TI  - Culture of red beet hairy roots by considering variation in sensitivity of tip
      meristems to hydraulic stress.
AB  - In the culture of red beet hairy roots in shaking flasks, a period for
      acclimation without lateral root generation existed at the early stage, and the
      root tip meristems containing growing points (GPs) were found to be damaged under
      an elevated shear stress condition. The loading experiments of shear stress to
      the hairy roots revealed that the GPs subjected to the acclimation acquired
      tolerance to shear stress, retaining relatively high viability of GPs up to
      0.6N/m(2) of loaded shear stress. Next, the hairy roots after culture for 50h at
      0.05N/m(2) of shear stress were exposed to conditions at various levels of shear
      stress in a single column reactor, and a relatively high growth rate was obtained
      in the vicinity of 1.0N/m(2) of shear stress. According to these results, two
      stage cultures of hairy roots were then performed, which was comprised of a first
      stage for 50h at 0.05N/m(2) of shear stress for the prevention of decay of the
      GPs caused by hydraulic stress and a second stage for 110h at 1.0N/m(2) of shear
      stress for active elongation of the GPs with sufficient nutrient supply by
      regulation of the medium flow rate. The cell concentration ultimately reached
      7.6kg dry cells/m(3), although no growth was observed in the case where the hairy
      roots did not undergo the first stage.

PMID- 10908862
TI  - alpha-Amylase immobilized on bulk acoustic-wave sensor by UV-curing coating.
AB  - A new method for immobilization of alpha-amylase by UV-curing coating is proposed
      in this paper. The immobilization procedure of UV-curing coating on piezoelectric
      quartz crystal is simple and convenient, and causes less loss of enzymatic
      activity. The activity of the immobilized alpha-amylase is monitored by a
      technique based on bulk acoustic-wave (BAW) sensor. The frequency shift of BAW
      sensor can reflect the degree of hydrolysis of starch by the immobilized alpha
      amylase. It is appropriate for the immobilized alpha-amylase to hydrolyze the
      soluble starch under pH 7.0 condition, which is similar to that of the free alpha
      amylase. Kinetic parameters (the Michaelis constant, K(m), and the maximum
      initial rate V(max)) of the enzymatic hydrolysis of starch by the immobilized
      alpha-amylase are estimated by using a linear method of Lineweaver-Burk plot.
      K(m)=12.7mgml(-1) and V(max)=15.9Hzmin(-1). And the experimental results show
      that the immobilized alpha-amylase entrapped by the UV-curing coating retains
      adequate enzymatic activity and can be reused more than 50 times under certain
      experimental conditions.

PMID- 10908863
TI  - Biomass production and biochemical variability of the marine microalga Isochrysis
      galbana in relation to culture medium.
AB  - We have studied the autotrophic growth of the marine microalga, Isochrysis
      galbana Parke, in a batch photobioreactor, comparing five different culture media
      and analysing the influence of each on growth kinetics as well as on the fatty
      acid composition and protein content of the biomass. All the experiments were
      performed at 15 degrees C, with the culture medium at pH 8.0, a specific rate of
      air supply of 1vv(-1)min(-1) and a continuous illumination of 40-43Wm(-2). The
      results show no parallel between good nutritional characteristics and high values
      of the kinetic parameters. Nevertheless, a compromise between the nutritional
      factors and growth kinetics could be provided by Ukeles medium, which provided a
      biomass with a good composition in polyunsaturated fatty acids (quotient
      n3/n6=3.2), an adequate protein content (25.3%) and relatively high values,
      although not the highest registered, for maximum specific growth rate
      (u(m)=0.018h(-1)) and biomass productivity (1.9x10(-3)kgm(-3)h(-1)).

PMID- 10908864
TI  - Lysozyme separation by hollow-fibre ultrafiltration.
AB  - This paper discusses the purification of lysozyme from chicken egg white using
      hollow-fibre ultrafiltration (30kDa MWCO, polysulphone membrane). Lysozyme is
      preferentially transmitted through the membrane while the membrane largely
      retains other egg white proteins. Improvement in system hydrodynamics resulted in
      an increase in permeate flux while lysozyme transmission remained unaffected,
      leading to higher productivity. The percentage purity of lysozyme obtained was
      generally insensitive to system hydrodynamics. The permeate flux and productivity
      increased with increase in transmembrane pressure (TMP) before levelling off
      around 0.7bar. However, the TMP did not have any pronounced effect on the
      transmission and the purity of lysozyme. Experiments carried out in the
      diafiltration mode showed that moderately pure lysozyme (80-90%) could be
      obtained in an extended operation.

PMID- 10908865
TI  - Single versus multiple bioreactor scale-up: economy for high-value products.
AB  - The economy of scaling-up a bioreactor by increasing the number of units was
      investigated with respect to an integrated flowsheet. For the production of t-PA
      from animal cells, a base case flowsheet using a single large bioreactor was
      compared to a multiple bioreactor case. Simulation of the complete flowsheets for
      the two cases showed that a multiple bioreactor approach to scale-up increases
      the return of investment (ROI) of the base process by 122%. This enormous
      increase in ROI results from the smaller size of the downstream units compared to
      the base case, since downstream processing accounts for about 80% of the total
      cost for high value products like t-PA. Proper scheduling of the downstream units
      allowed sharing of the equipment by the bioreactors. A breakdown of the equipment
      purchase cost showed that cost related to cell culture equipment increased from
      14% for the base case to about 37% for the multiple bioreactor case. The
      contribution from chromatography columns to the total equipment purchase cost, on
      the other hand, decreased from 52 to 33%.

PMID- 10908866
TI  - Optimization of the production of aroma compounds by Kluyveromyces marxianus in
      solid-state fermentation using factorial design and response surface methodology.
AB  - Studies were carried out for the production of aroma compounds in solid-state
      fermentation using factorial design and response surface methodology (RSM)
      experiments. Five agro-industrial residues were evaluated as substrate for
      cultivating a strain of Kluyveromyces marxianus. The results proved the
      feasibility of using cassava bagasse and giant palm bran (Opuntia ficus indica)
      as substrates to produce fruity aroma compounds by the yeast culture. In order to
      test the influence of the process parameters on the culture to produce volatile
      compounds, two statistical experimental designs were performed. The parameters
      studied were initial substrate pH, addition of glucose, cultivation temperature,
      initial substrate moisture and inoculum size. Using a 2(5) factorial design,
      addition of glucose and initial pH of the substrate was found statistically
      significant for aroma compounds production on palm bran. Although this
      experimental design showed that addition of glucose did not have a significant
      role with cassava bagasse, 2(2) factorial design revealed that glucose addition
      was significant at higher concentrations. Head-space analysis of the culture by
      gas chromatography showed the production of nine and eleven compounds from palm
      bran and cassava bagasse, respectively, which included alcohols, esters and
      aldehyde. In both the cases, two compounds remained unidentified and ethyl
      acetate, ethanol and acetaldehyde were the major compounds produced. Esters
      produced were responsible for the fruity aroma in both the cases. With palm bran,
      ethanol was the compound produced in highest concentration, and with cassava
      bagasse (both supplemented with 10% glucose), ethyl acetate was produced at
      highest concentration, accumulating 418 and 1395umoll(-1) head-spaceg(-1)
      substrate in 72h, respectively.

PMID- 10908867
TI  - Characterisation of small molecules diffusion in hydrogel-membrane liquid-core
      capsules.
AB  - The overall diffusion coefficients for several low molecular weight solutes, such
      as glucose, fructose, sucrose, lactose, and vitamin B(12) have been determined in
      Ca-alginate membrane liquid-core capsules using the unsteady-state method
      following the release of solutes from the capsules to a well-stirred solution of
      limited volume. The diffusion coefficients obtained for saccharides were 5-20%
      lower than the corresponding diffusivity in water while for vitamin B(12) about
      50% that of water. The diffusion coefficients of the investigated capsules were
      not influenced by the change in alginate concentration in the capsule membrane
      from 0.5 to 1.0%. Lower diffusivities and higher deviations from the diffusivity
      in water were obtained for higher molecular weight solutes.

PMID- 10908868
TI  - Phenol biodegradation by Pseudomonas putida DSM 548 in a batch reactor.
AB  - Phenol biodegradation in a batch reactor using a pure culture of Pseudomonas
      putida DSM 548 was studied. The purpose of the experiments was to determine the
      kinetics of biodegradation by measuring biomass growth rates and phenol
      concentration as a function of time in a batch reactor. The Haldane equation
      u=u(m)S/((K(s)+S+S(2))/K(i)) adequately describes cell growth with kinetic
      constants u(m)=0.436h(-1), K(s)=6.19mgl(-1), K(i)=54.1mgl(-1). These values are
      in the range of those published in literature for pure or mixed cultures
      degrading phenol.

PMID- 10908869
TI  - A study for multiple steady states of biochemical reactions under substrate and
      product inhibition.
AB  - This paper combines Sturm's method with the tangent analysis method to solve a
      biochemical reaction involving multiplicity. This method can easily derive the
      necessary conditions for multiplicity. In addition, we find a starting
      bifurcation point for multiplicity which cannot be obtained by the tangent method
      alone. Moreover, a start-up strategy is suggested to obtain a high conversion and
      unique steady state in four selected kinetic models of biochemical reactions,
      with inhibition.

PMID- 10908870
TI  - Microbial production of 2-chloro-alpha-methylbenzyl alcohol and its adsorptive
      recovery.
AB  - An adsorptive process was combined with yeast-mediated production of chiral 2
      chloro-alpha-methylbenzyl alcohol (o-Cl-1-PA) for effective product recovery and
      reuse of the reaction medium. Low temperature was suitable for long-term reactor
      operation, and continuous production using a shallow-bed reactor was achieved for
      at least 22 days while maintaining a high conversion. The appropriate size of the
      adsorption column for product recovery from the reactor effluent was estimated
      through measurement of breakthrough curves of o-Cl-1-PA in a packed bed of the
      resin at various adsorbate concentrations and feed flow rates. Using the
      adsorption column, 98% of the product and the residual substrate were recovered
      from the reactor effluent, and the effluent from the adsorption column was
      successfully reused as the reaction medium after microfiltration to save the
      medium consumption.

PMID- 10908871
TI  - Characterization of energy conversion based on metabolic flux analysis in
      mixotrophic liverwort cells, Marchantia polymorpha.
AB  - In order to characterize the contributions of respiratory and photosynthetic
      actions to energy conversions, the mixotrophic cells of Marchantia polymorpha
      were cultivated in the medium containing 10kg/m(3) glucose as an organic carbon
      source. The cultures were conducted with the supply of ordinary air (0.03% CO(2))
      at constant incident light intensities of 50 and 180W/m(2). From the results of
      metabolic analysis, it was found that the cell yield based on ATP synthesis was
      estimated to be 6.3x10(-3)kg-dry cells/mol-ATP in these cultures. Under the
      examined conditions, energy conversion efficiency through respiration was larger
      than that through photosynthesis, and efficiency of overall energy conversion to
      ATP was maximized when the sum of energies from glucose and light captured by the
      cells was approximately 7.2x10(5)J/(hkg-dry cells). Taking into account the
      efficiency of overall energy conversion, a batch culture of M. polymorpha in a
      bioreactor was carried out by regulating incident light intensity ranging from 9
      to 58W/m(2). In the culture with light regulation, the cell yield of 6.2x10(-9)kg
      dry cells/J was achieved on the basis of energy provided to the system throughout
      the culture, and this value was 2.3 and 9.3 times as large as those obtained in
      the cultures under constant incident light intensities of 50 and 180W/m(2),
      respectively.

PMID- 10908872
TI  - Viability of plant hairy roots is sustained without propagation in low sugar
      medium kept at ambient temperature.
AB  - The effect of sucrose concentration in the medium on the growth and resumption
      ability to form lateral roots was investigated using the hairy roots of pak-bung
      and tobacco. It was found that the growth evaluated by root tip elongation of pak
      bung and tobacco hairy roots was suppressed in the medium having an initial
      sucrose concentration of <2.5kg/m(3), and that the resumption abilities of both
      the hairy roots could be preserved when the hairy roots were kept at an initial
      sucrose concentration of 2.5kg/m(3) under ambient temperature conditions. The
      values of maintenance energy for pak-bung and tobacco hairy roots were determined
      to be 0.11 and 0.12 per day, respectively, from the total sugar consumption
      rates. Under the oligotrophic condition of the sucrose concentration of
      2.5kg/m(3), the hairy roots were considered to exist as resting cells with
      maintenance metabolism, and the minimum demand for the energy source to ensure
      survival of the cells was met because the cells hardly multiplied and sugar
      consumption was not significant. In addition, long-term storage of pak-bung hairy
      roots in the liquid medium with 2.5kg/m(3) sucrose was performed at 25 degrees C.
      It was demonstrated that the hairy roots could maintain their resumption
      abilities without a serious loss of viability over 600 days and that the number
      of budding lateral roots per unit length of the main roots remained a value of 72
      roots/m after the 600-day storage.

PMID- 10908873
TI  - A reverse trend--MADS functions revealed.

PMID- 10908875
TI  - Announcement

PMID- 10908874
TI  - The dawn of plant salt tolerance genetics.

PMID- 10908876
TI  - Regulation of lysine catabolism in higher plants.
AB  - Lysine is an essential amino acid for mammals but its concentration in cereals,
      one of our main food sources, is low. Research over the past 40 years has
      unraveled many biochemical and molecular details of the aspartic acid pathway,
      which is the main route of lysine biosynthesis in plants. However, genetic
      manipulation of this pathway has not been successful at producing high-lysine
      seeds. This is because lysine, instead of being accumulated, is degraded via the
      saccharopine pathway. Recent work has increased our knowledge of this pathway,
      including both the enzymes involved and their regulation.

PMID- 10908877
TI  - Recent progress in reconstructing angiosperm phylogeny.
AB  - In the past year, the study of angiosperm phylogeny has moved from tentative
      inferences based on relatively small data matrices into an era of sophisticated,
      multigene analyses and significantly greater confidence. Recent studies provide
      both strong statistical support and mutual corroboration for crucial aspects of
      angiosperm phylogeny. These include identifying the earliest extant lineages of
      angiosperms, confirming Amborella as the sister of all other angiosperms,
      confirming some previously proposed lineages and redefining other groups
      consistent with their phylogeny. This phylogenetic framework enables the
      exploration of both genotypic and phenotypic diversification among angiosperms.

PMID- 10908878
TI  - Plant blue-light receptors.
AB  - Plants have several blue-light receptors, which regulate different aspects of
      growth and development. Recent studies have identified three such receptors:
      cryptochrome 1, cryptochrome 2 and phototropin. Cryptochromes 1 and 2 are
      photolyase-like receptors that regulate hypocotyl growth and flowering time;
      phototropin mediates phototropism in response to blue light. In addition,
      phytochrome A has also been found to mediate various blue-light responses.
      Although the signal-transduction mechanisms of blue-light receptors remain
      largely unclear, phototropin is probably a protein kinase that regulates
      cytoplasmic calcium concentrations, whereas the cryptochromes might regulate
      anion-channel activity and changes in gene expression.

PMID- 10908879
TI  - Closing the ranks to attack by powdery mildew.
AB  - Powdery mildews are among the most common plant diseases, infecting over 650
      monocot and over 9000 dicot species. Analysis in domesticated barley and wild
      Arabidopsis has begun to unravel the genetic and molecular frameworks underlying
      the mechanisms of susceptibility and resistance to these biotrophic fungal
      pathogens. This has revealed multiple pathways regulating host defense, some of
      which are also involved in determining the host range of the pathogen. Host-cell
      death and rapid cell-wall remodeling have emerged as frequent themes in powdery
      mildew resistance. Several mutants have been isolated that might shed light on
      the enigma of susceptibility determinants in plants.

PMID- 10908880
TI  - Age-related changes in photosynthesis of woody plants.
AB  - Woody peoffnials do not appear to go through a defined senescence phase but do
      have predictable developmental stages. Reduced photosynthesis and stomatal
      conductance have been reported at all developmental transitions, although some
      studies have shown the opposite. What causes these changes and why do results
      differ among studies? Do these changes result from or cause changes in growth?
      What are the roles of genetics, size, changing conditions and cumulative
      environmental stress in aging trees? Definitive answers remain elusive but recent
      research is helping to clarify some of the processes associated with aging and to
      point the way for further study.

PMID- 10908881
TI  - Agrobacterium-mediated plant transformation with large DNA fragments.

PMID- 10908882
TI  - Inositol signaling and plant growth

PMID- 10908883
TI  - Ubiquitous pathogens: links between infection and autoimmunity in MS?

PMID- 10908884
TI  - Alzheimer's disease: what is it, how many people have it, and why do we need to
      know?

PMID- 10908885
TI  - Paroxysmal movement disorders and epilepsy: links across the channel.

PMID- 10908886
TI  - Clinical utility of surface EMG: report of the therapeutics and technology
      assessment subcommittee of the American Academy of Neurology.

PMID- 10908887
TI  - Association between clinical disease activity and Epstein-Barr virus reactivation
      in MS.
AB  - OBJECTIVE: To assess the potential significance of Epstein-Barr virus (EBV)
      reactivation in disease activity in MS patients. METHODS: The prevalence of
      antibodies against herpes simplex virus type 1 (HSV-1), HSV-2, EBV, and
      cytomegalovirus was determined in a group of 108 MS patients and in 163 healthy
      control subjects. Sera were analyzed using combinations of novel assay systems
      employing highly purified viral and recombinant antigens. In addition, PCR for
      the detection of EBV DNA was performed in serial samples. RESULTS: In contrast to
      the control populations, antibodies against EBV were present in 100% of MS
      patients. Among the tested human herpesviruses, this high extent of
      seropositivity was only found for EBV. Primary infection was found exclusively in
      the control group (3.7%), whereas serologic evidence of EBV reactivation was seen
      in MS patients (13. 9%) as well as control subjects (17.2%). There was no
      temporal coincidence between EBV reactivation and disease activity in MS
      patients. However, in 19 patients followed monthly for 1 year, active viral
      replication as measured by increased immunoglobulin (Ig) M and IgA responses to
      EBV early antigens (p54 + p138) and positive serum DNA was seen in 72.7% of
      patients with exacerbations during the study period and in none of the patients
      with clinically stable disease. CONCLUSIONS: The results demonstrate an
      association between EBV reactivation and disease activity in MS patients over
      time, and suggest that EBV might play an indirect role in MS as an activator of
      the underlying disease process.

PMID- 10908888
TI  - A longitudinal study of T1 hypointense lesions in relapsing MS: MSCRG trial of
      interferon beta-1a. Multiple Sclerosis Collaborative Research Group.
AB  - BACKGROUND: T1 hypointense lesions (T1 black holes) are focal areas of relatively
      severe CNS tissue damage detected by MRI in patients with MS. OBJECTIVE: To
      determine the natural history of T1 hypointense lesions in relapsing MS and the
      utility of T1 hypointense lesions as outcome measures in MS clinical trials.
      METHODS: MR studies were from the Multiple Sclerosis Collaborative Research Group
      trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a
      (IFNbeta-1a)-treated patients with mild to moderate disability relapsing
      remitting MS. RESULTS: There was a small but significant correlation between T1
      hypointense lesion volume and disability at baseline and on trial (r = 0.22, r =
      0.28). In placebo patients there was a 29.2% increase in the mean volume of T1
      hypointense lesions (median 124.5 mm3) over 2 years (p < 0.001 for change from
      baseline), as compared to an 11.8% increase (median 40 mm3) in the IFNbeta-1a
      treated patients (change from baseline not significant). These treatment group
      comparisons did not quite reach significance. The most significant contributor to
      change in T1 hypointense lesions was the baseline number of enhancing lesions
      (model r2 = 0.554). Placebo patients with more active disease, defined by
      enhancing lesions at baseline, were the only group to show a significant increase
      in T1 hypointense lesion volume from baseline. CONCLUSION: The development of T1
      hypointense lesions is strongly influenced by prior inflammatory disease
      activity, as indicated by enhancing lesions. These results suggest that treatment
      with once weekly IM IFNbeta-1a (30 mcg) slows the 2-year accumulation of these
      lesions in the brain.

PMID- 10908889
TI  - Defective regulation of IFNgamma and IL-12 by endogenous IL-10 in progressive MS.
AB  - BACKGROUND: MS is a chronic inflammatory disease of the CNS postulated to be a
      Th1 type cell-mediated autoimmune disease. There is increased interferon-gamma
      (IFNgamma) secretion in MS, and IFNgamma administration induces exacerbations of
      disease. IFNgamma expression is closely regulated by a number of cytokines
      produced by different cells of the immune system. Interleukin-12 (IL-12) is a
      major factor leading to Th1-type responses, including IFNgamma secretion, and
      there is increased secretion of IL-12 in MS. IL-10 is a potent inhibitor of both
      IL-12 and IFNgamma expression. METHODS: The authors investigated cytokine
      production and proliferative responses of peripheral blood mononuclear cells
      stimulated with soluble anti-CD3 in healthy controls and patients with stable
      relapsing-remitting MS or progressive MS. RESULTS: The authors found that T cell
      receptor-mediated IFNgamma and IL-10 secretion were increased in progressive MS,
      whereas IL-4 and IL-2 secretion and lymphocyte proliferative responses were
      normal. Anti-IL-12 antibody suppressed raised IFNgamma in progressive MS but did
      not affect raised IL-10. In addition, neutralization of endogenous IL-10
      upregulated IFNgamma in controls but not progressive MS. IL-10 was produced by
      CD4+ cells whereas IFNgamma was produced by both CD4+ and CD8+ cells. There were
      no differences in IL-10 receptor expression in MS patients. CONCLUSIONS: These
      abnormalities in IL-10 regulation were not seen in the relapsing-remitting form
      of MS. Thus, the defect in regulation of both IL-12 and IFNgamma production by
      endogenous IL-10 in progressive MS could be an important factor involved in the
      transition of MS from the relapsing to the progressive stage and has implications
      for treating MS patients with exogenous IL-10.

PMID- 10908890
TI  - Prevalence of AD among whites: a summary by levels of severity.
AB  - OBJECTIVE: To determine age- and sex-specific AD prevalence rates for whites
      using each of four severity-based definitions of a case: a person diagnosed as
      having at least questionable AD, one diagnosed as having at least mild AD, one
      diagnosed as having moderate or severe AD, and one diagnosed as having severe AD.
      METHODS: Data from 21 studies of Europeans and North Americans were pooled.
      RESULTS: Empirically, one study, from East Boston, is an outlier. Applied to the
      US population of 1996, the obtained estimates yield a prevalence of 1.7 to 1.9
      million cases, depending on whether the outlier study is excluded or included.
      CONCLUSIONS: With disease severity taken into account, estimates of AD prevalence
      from white populations are more consistent than is usually acknowledged. By
      including disease severity in the case definition, variations in reported rates
      are much reduced. The outlier status of the East Boston study appears to result
      from the use of a definition of AD that differs from that used in the other 20
      studies. Alternative explanations of the discrepancy between these estimates and
      the common estimate of 4 million cases are discussed.

PMID- 10908891
TI  - PET shows that striatal dopamine D1 and D2 receptors are differentially affected
      in AD.
AB  - OBJECTIVE: To study dopamine D1 and D2 receptors in the putamen and the caudate
      nucleus in patients with AD and age-matched healthy controls by means of PET.
      METHODS: A dopamine D1 receptor antagonist ([11C]NNC 756) and a D2 receptor
      antagonist ([11C]raclopride) were used as ligands. The uptake of these ligands
      was calculated as a distribution volume ratio of the putamen and the caudate
      nucleus to the cerebellum. RESULTS: The mean [11C]NNC 756 uptake in AD was
      reduced by 14% from the mean control value both in the putamen (p = 0.004) and
      the caudate nucleus (p = 0.009). There was no significant reduction in the mean
      [11C]raclopride uptake in either the putamen or the caudate nucleus in AD. There
      was no correlation between [11C]NNC 756 or [11C]raclopride uptake and Mini-Mental
      State Examination or motor Unified PD Rating Scale scores in patients with AD.
      CONCLUSIONS: There are changes in striatal D1 but not in D2 receptors in AD.

PMID- 10908892
TI  - Access www.neurology.org now for full-text articles

PMID- 10908894
TI  - Activate your online subscription

PMID- 10908895
TI  - A milestone for normal development of the infantile brain detected by functional
      MRI.
AB  - OBJECTIVE: To investigate the relationship between cerebral cortical function and
      white matter myelination in the visual pathway in the evaluation of normal brain
      development. METHODS: The authors performed quantitative analysis of white matter
      myelination detected with conventional T1-weighted spin echo (SE) MRI and brain
      functional MRI (fMRI) using echoplanar imaging with photic stimulation in 27
      neurologically normal infants (age range, 0 to 22 weeks). RESULTS: An age
      dependent gradual increase in signal intensity was observed in optic radiation on
      the T1-weighted SE images, indicating progression of white matter myelination. A
      rapid age-dependent reverse in signal response was observed on fMRI. Infants
      older than 8 weeks showed a stimulus-induced signal decrease in the visual
      cortex, whereas infants younger than 7 weeks showed a signal increase.
      CONCLUSIONS: A rapid inversion of response revealed by fMRI with photic
      stimulation in infants suggests a change in oxygen consumption during neuronal
      activation, which is related to rapid synapse formation and accompanying
      increased metabolism. fMRI can detect dynamic metabolic changes during brain
      maturation, which is a different developmental process from white matter
      myelination. The metabolic changes detected by fMRI provide a milestone for the
      evaluation of normal brain development.

PMID- 10908893
TI  - Regional metabolic patterns in mild cognitive impairment and Alzheimer's disease:
      A 1H MRS study.
AB  - BACKGROUND: Mild cognitive impairment (MCI) is a recently described transitional
      clinical state between normal aging and AD. Assuming that amnestic MCI patients
      had pathologic changes corresponding to an early phase and probable AD patients
      to a later phase of the disease progression, the authors could approximate the
      temporal course of proton MR spectroscopic (1H MRS) alterations in AD with a
      cross-sectional sampling scheme. METHODS: The authors compared 1H MRS findings in
      the superior temporal lobe, posterior cingulate gyri, and medial occipital lobe
      in 21 patients with MCI, 21 patients with probable AD, and 63 elderly controls.
      These areas are known to be involved at different neurofibrillary pathologic
      stages of AD. RESULTS: The N-acetylaspartate (NAA)/creatine (Cr) ratios were
      significantly lower in AD patients compared to both MCI and normal control
      subjects in the left superior temporal and the posterior cingulate volumes of
      interest (VOI) and there were no between-group differences in the medial
      occipital VOI. Myoinositol (MI)/Cr ratios measured from the posterior cingulate
      VOI were significantly higher in both MCI and AD patients than controls. The
      choline (Cho)/Cr ratios measured from the posterior cingulate VOI were higher in
      AD patients compared to both MCI and control subjects. CONCLUSION: These findings
      suggest that the initial 1H MRS change in the pathologic progression of AD is an
      increase in MI/Cr. A decrease in NAA/Cr and an increase in Cho/Cr develop later
      in the disease course.

PMID- 10908897
TI  - Cognitive outcome of children with epilepsy and malformations of cortical
      development.
AB  - OBJECTIVE: To assess intellectual functioning (IQ) in 54 children and adolescents
      with intractable epilepsy who later underwent cortical resection due to
      unilateral malformations of cortical development acquired in utero. METHODS:
      Lesion type was classified into circumscribed mass lesions and diffuse cortical
      dysplasia based on histopathologic analysis of surgical tissue. Cortical
      dysplastic lesions were further graded as mild, moderate, or severe according to
      specific microscopic features. Laterality of lesion was determined through
      neurologic examination and electrophysiologic and neuroradiologic procedures.
      Classification of lesion type was corroborated by its significant relationship
      with other disease-related variables known to be related to clinical severity
      (age at seizure onset, age at resection, and extent of lesion). RESULTS: Analyses
      of covariance revealed that circumscribed lesions had a less deleterious effect
      on nonverbal IQ than did diffuse cortical dysplasia, after controlling for age at
      seizure onset and extent of lesion. This effect was also found on verbal IQ
      measures, but only in subjects with right-sided lesions. Subjects with left-sided
      lesions performed significantly more poorly on verbal IQ measures than those with
      right-sided lesions. Additionally, younger age at onset and greater extent of
      lesion were associated with poorer cognitive outcome. CONCLUSIONS: Cortical
      dysplasia and early left hemisphere lesions have a significantly worse impact on
      cognitive functioning than circumscribed lesions or right hemisphere
      developmental lesions in children with epilepsy.

PMID- 10908896
TI  - Paroxysmal kinesigenic dyskinesia and infantile convulsions: clinical and linkage
      studies.
AB  - OBJECTIVE: To clinically characterize affected individuals in families with
      paroxysmal kinesigenic dyskinesia (PKD), examine the association with infantile
      convulsions, and confirm linkage to a pericentromeric chromosome 16 locus.
      BACKGROUND: PKD is characterized by frequent, recurrent attacks of involuntary
      movement or posturing in response to sudden movement, stress, or excitement.
      Recently, an autosomal dominant PKD locus on chromosome 16 was identified.
      METHODS: The authors studied 11 previously unreported families of diverse ethnic
      background with PKD with or without infantile convulsions and performed linkage
      analysis with markers spanning the chromosome 16 locus. Detailed clinical
      questionnaires and interviews were conducted with affected and unaffected family
      members. RESULTS: Clinical characterization and sampling of 95 individuals in 11
      families revealed 44 individuals with paroxysmal dyskinesia, infantile
      convulsions, or both. Infantile convulsions were surprisingly common, occurring
      in 9 of 11 families. In only two individuals did generalized seizures occur in
      later childhood or adulthood. The authors defined a 26-cM region using linkage
      data in 11 families (maximum lod score 6.63 at theta = 0). Affected individuals
      in one family showed no evidence for a shared haplotype in this region, implying
      locus heterogeneity. CONCLUSIONS: Identification and characterization of the
      PKD/infantile convulsions gene will provide new insight into the pathophysiology
      of this disorder, which spans the phenotypic spectrum between epilepsy and
      movement disorder.

PMID- 10908898
TI  - Levetiracetam for partial seizures: results of a double-blind, randomized
      clinical trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of 500 mg bid and 1500 mg bid
      levetiracetam as adjunctive therapy for refractory partial seizures in a double
      blind, randomized, placebo-controlled, parallel-group, multicenter trial.
      METHODS: The authors studied patients with uncontrolled partial seizures (minimum
      12 per 12 weeks), regardless of whether they became secondarily generalized, for
      38 weeks. A 12-week baseline was followed by random assignment to adjunctive
      therapy with placebo (n = 95), levetiracetam 1000 mg/day (n = 98), or
      levetiracetam 3000 mg/day (n = 101). Upward titration over 4 weeks was followed
      by 14 weeks of fixed dose treatment, and concluded with an 8-week medication
      withdrawal period or entering a follow-up study. RESULTS: Of 294 patients
      randomized, 268 completed the study. Partial seizure frequency during the entire
      evaluation period (primary efficacy variable) was lower with levetiracetam
      compared to placebo (p </= 0.001 for both groups). More patients responded
      (defined as minimum 50% reduction in partial seizure frequency) to levetiracetam
      than placebo, with rates of 33. 0% in the 1000 mg/day and 39.8% in the 3000
      mg/day group, compared to 10.8% in the placebo group (p < 0.001). Of 199 patients
      receiving levetiracetam, 11 became seizure free; no patient became seizure free
      in the placebo group. Treatment-emergent adverse events (>/=10%), mostly mild to
      moderate in severity, with incidences higher than placebo were asthenia,
      dizziness, flu syndrome, headache, infection, rhinitis, and somnolence.
      CONCLUSION: Adjunctive therapy with levetiracetam was effective and well
      tolerated in controlling partial seizures.

PMID- 10908899
TI  - Postoperative hippocampal remnant shrinkage and memory decline: a dynamic
      process.
AB  - BACKGROUND: The severity of postoperative memory decline in unilateral temporal
      lobectomy patients has been associated both with the extent of hippocampal
      resection and MRI measures of preoperative hippocampal volume. Serial MRI of the
      hippocampal remnant suggest that further volume loss occurs in the immediate
      postoperative period. For the majority of patients, this process appears to
      stabilize within the first 3 months. The authors examined the relationship
      between the dynamic volume of the hippocampal remnant and postoperative memory
      decline. METHOD: Seventeen adult temporal lobectomy patients (nine, left; eight,
      right) underwent a full neuropsychological assessment and a volumetric MRI scan
      preoperatively and 3 months postoperatively. Examination of the posterior
      hippocampal remnant on the postoperative scan revealed volume loss in this
      segment compared to the identical segment preoperatively in 16 of 17 cases.
      Spearman's correlations were used to examine the relationship between
      postoperative memory decline (postoperative - preoperative memory scores) and the
      postoperative/preoperative hippocampal remnant volume ratio. RESULTS: The volume
      of the hippocampal remnant left in situ was significantly correlated with
      postoperative memory change. Patients with smaller remnant volumes demonstrated
      more postoperative memory decline than those with larger remnants. In addition,
      extensive hippocampal remnant shrinkage was associated with postoperative memory
      decline in both the right and left temporal lobectomy groups. CONCLUSIONS: The
      absolute volume and subsequent volume loss in the hippocampal remnant following
      surgery can influence postoperative memory change. These findings suggest that
      postoperative processes should be considered in addition to preoperative
      pathology and surgical factors in the prediction of postoperative memory change.

PMID- 10908900
TI  - Alterations in bcl-2 and caspase gene family protein expression in human temporal
      lobe epilepsy.
AB  - OBJECTIVE: To address the role of cell death regulatory genes of the bcl-2 and
      caspase families in the neuropathology of human epilepsy using tissue extracted
      from patients undergoing temporal lobectomy for intractable seizures. METHODS:
      Using Western blotting and immunohistochemistry, the authors investigated the
      expression of bcl-2, bcl-xL, bax, caspase-1,and caspase-3 in temporal cortex
      samples from patients who had undergone temporal lobectomy surgery for
      intractable epilepsy (n = 19). Nonepileptic postmortem tissue from a brain bank
      served as control (n = 6). RESULTS: Western blot analysis demonstrated
      significant increases in levels of bcl-2 and bcl-xL protein in seizure brain
      compared to control. Cleavage of caspase-1 was evidenced by a reduction in levels
      of the 45 kDa proenzyme form and an increase in levels of the p10 fragment.
      Levels of the 32 kDa proenzyme form of caspase-3 were elevated in seizure
      patients, as were levels of the 12 kDa cleaved fragment. Bcl-2, bax, and caspase
      3 immunoreactivity was increased predominantly in cells with the morphologic
      appearance of neurons, whereas bcl-xL immunoreactivity was increased in cells
      with the appearance of glia. DNA fragmentation was detected in some but not all
      sections from epileptic brain samples. CONCLUSIONS: Cell death regulatory genes
      of the bcl-2 and caspase families may play a role in ongoing neuropathologic
      processes in human epilepsy, and offer novel targets as an adjunct to
      anticonvulsant therapy.

PMID- 10908901
TI  - Anticonvulsant prophylaxis and timing of seizures after aneurysmal subarachnoid
      hemorrhage.
AB  - OBJECTIVE: There is no evidence that seizure prophylaxis is indicated after
      aneurysmal subarachnoid hemorrhage (SAH). This study examines prophylactic
      antiepileptic drug (AED) prescription and the occurrence of seizures within a
      single university-affiliated institution. METHODS: The authors reviewed 95 SAH
      patient charts using standardized forms. Variables included prophylaxis duration,
      seizure incidence and timing, CT findings, AED adverse events, and 1-year patient
      follow-up. RESULTS: Prehospital seizures occurred in 17.9% (17/95) of patients;
      another 7.4% (7/95) had a questionable prehospital seizure. In-hospital seizures
      occurred in 4.1% (4/95) of patients, a mean of 14.5 +/- 13.7 days from ictus;
      three of these four patients were receiving an AED at the time of seizure.
      Inpatient AED were prescribed to 99% of the cohort for a median of 12 (range 1 to
      68) days. Approximately 8% of the cohort had posthospital discharge seizures;
      this included the patients who had prehospital or in-hospital seizures, 50% of
      whom were receiving AED therapy at the time of the seizure. Adverse effects
      occurred in 4. 1%; none were serious. The thickness of cisternal clot was
      associated with having a seizure; no other clinical predictors were identified.
      Having a seizure at any time did not adversely affect outcome. CONCLUSIONS: In
      this SAH population, the majority of seizures happened before medical
      presentation. In-hospital seizures were rare and occurred more than 7 days
      postictus for patients receiving AED prophylaxis. The vast majority of putative
      clinical predictors did not help predict the occurrence of seizures; only the
      thickness of the cisternal clot was of value in predicting seizures. Patient
      selection for and the efficacy and timing of AED prophylaxis after SAH deserve
      prospective evaluation.

PMID- 10908902
TI  - Significance of hyperintense vessels on FLAIR MRI in acute stroke.
AB  - OBJECTIVE: To describe hyperintense vessels sign (HVS) in patients with acute
      stroke on fluid-attenuated inversion recovery (FLAIR) MRI and determine its
      clinical significance and utility. BACKGROUND: Enhancement of vessels on
      postcontrast MRI in patients with acute stroke is considered an indicator of
      early brain ischemia. Recently, the FLAIR technique has shown promise in earlier
      and better detection of ischemic brain parenchymal lesions. METHODS: Two
      observers retrospectively reviewed 304 MRI of patients with stroke and identified
      30 patients with acute middle cerebral artery stroke and HVS on FLAIR obtained
      within 24 hours of symptom onset. These patients were evaluated with contrast
      enhanced MRI (n = 9), MR angiography of carotid and intracranial circulation (n =
      30), cerebral angiography (n = 8), transcranial Doppler (n = 17), and SPECT (n =
      16). The extent of HVS was compared with final infarct size and NIH Stroke Scale
      score. RESULTS: HVS on FLAIR was seen in 10% of the patients with acute stroke.
      HVS was associated with large vessel occlusion or severe stenosis (>90%).
      Intravascular enhancement on contrast MRI was observed in vessels that were
      hyperintense on FLAIR. Both cortical and subcortical infarcts demonstrated HVS.
      MR angiographic and cerebral angiographic findings of large vessel occlusion or
      severe stenosis (>90%), slow flow, low velocities by transcranial Doppler, and
      hypoperfusion on SPECT correlated with HVS. HVS was the earliest ischemic change
      in three patients scanned within 3 hours of ictus. Final infarct size was smaller
      than the area showing HVS in all patients. CONCLUSION: HVS on FLAIR MRI is an
      indicator of slow flow and early ischemia as a result of large vessel occlusion
      or stenosis and inadequacy of collateral circulation. HVS does not mean that
      infarction has occurred but indicates brain tissue at risk of infarction. It
      should prompt consideration of revascularization and flow augmentation
      strategies.

PMID- 10908903
TI  - Ischemic stroke in young women: risk of recurrence during subsequent pregnancies.
      French Study Group on Stroke in Pregnancy.
AB  - OBJECTIVE: To assess whether subsequent pregnancies increase the risk of
      recurrent stroke and whether the occurrence of an ischemic stroke affects
      reproductive history. METHODS: The authors identified 489 consecutive women aged
      15 to 40 years with a first-ever arterial ischemic stroke or cerebral venous
      thrombosis from the record system of nine French neurologic centers. Information
      on stroke recurrence and reproductive history was obtained by means of chart
      review, written questionnaire, and telephone interview. RESULTS: Data were
      analyzed from 441 women (373 with arterial ischemic stroke and 68 with cerebral
      venous thrombosis). During a mean follow-up of 5 years, 13 arterial recurrent
      ischemic strokes occurred. There were no cases of recurrent cerebral venous
      thrombosis. The overall risk of recurrence was 1% within 1 year and 2.3% within 5
      years. The risk of recurrence was significantly higher in patients with stroke of
      definite cause. Eleven recurrent strokes occurred outside pregnancy (absolute
      risk of recurrence = 0.5%; 95% CI 0.3, 0.95) and two during pregnancy or the
      puerperium (absolute risk of recurrence = 1. 8%; 95% CI 0.5, 7.5). The relative
      risk of recurrence was significantly higher during the postpartum period (risk
      ratio = 9.7; 95% CI 1.2, 78.9) than during pregnancy (risk ratio = 2.2; 95% CI 0.
      3, 17.5) itself. The outcome of the 187 subsequent pregnancies was similar to
      that expected from the general population. Thirty-four percent of women indicated
      that they would have desired more pregnancies after their initial stroke. The
      main reasons for not considering pregnancy were concern of a recurrent stroke,
      medical advice against pregnancy, and residual handicap. CONCLUSION: Young women
      with a history of ischemic stroke have a low risk of recurrence during subsequent
      pregnancies. The postpartum period, not the pregnancy itself, is associated with
      an increased risk of recurrent stroke. The outcome of pregnancies in these women
      appears to be similar to that expected in the general population. A previous
      ischemic stroke is not a contraindication to a subsequent pregnancy.

PMID- 10908905
TI  - Kayser-fleischer corneal ring

PMID- 10908904
TI  - Autosomal dominant Emery-Dreifuss dystrophy due to mutations in rod domain of the
      lamin A/C gene.
AB  - BACKGROUND: Autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD-AD) is a
      disorder characterized clinically by humeropelvic weakness, contractures, and
      cardiomyopathy, and genetically by mutations in the lamin A/C gene on 1q21.2
      q21.3. Of the 14 lamin A/C gene mutations reported thus far, the four involving
      the rod domain have been associated with isolated cardiomyopathy and conduction
      system disease. This is the first report of rod domain mutations in patients with
      the full EDMD-AD phenotype. METHODS: Clinical, pathologic, and genetic data are
      provided on two families with EDMD-AD. RESULTS: In both families, the full
      clinical spectrum of EDMD-AD was demonstrated. For the proband in family 1,
      sequence analysis detected a mutation within exon 2 of the lamin A/C gene. The
      missense mutation was due to a A448C base substitution causing a Thr150Pro amino
      acid change. For the proband of family 2, sequence analysis detected an in-frame
      3-bp deletion (AAG 778-780 or 781-783) removing one of two adjacent lysine
      residues (K 260 or 261) of exon 4. Both mutations were in the central rod domain
      of the lamin A/C gene. CONCLUSIONS: Mutations in the rod domain of the lamin A/C
      gene may cause the full clinical spectrum of EDMD-AD.

PMID- 10908906
TI  - Hallucinations, REM sleep, and Parkinson's disease: a medical hypothesis.
AB  - BACKGROUND: Patients with PD can have disabling visual hallucinations associated
      with dopaminergic therapy. Sleep disorders, including vivid dreams and REM sleep
      with motor behaviors (RBD), are frequent in these patients. METHODS: The
      association of hallucinations and REM sleep both at night and during the day was
      examined in 10 consecutive nondemented patients with long-standing levodopa
      responsive PD and hallucinations. Seven patients presented with paranoia and
      paranoid delusions. Overnight sleep recordings and standard multiple daytime
      sleep latency test were performed. The results were compared to those of 10
      similar patients with PD not experiencing hallucinations. RESULTS: RBD was
      detected in all 10 patients with hallucinations and in six without. Although
      nighttime sleep conditions were similar in both groups, hallucinators tended to
      be sleepier during the day. Delusions following nighttime REM period and daytime
      REM onsets were observed in three and eight of the hallucinators, and zero and
      two of the others. Daytime hallucinations, coincident with REM sleep intrusions
      during periods of wakefulness, were reported only by hallucinators. Postmortem
      examination of the brain of one patient showed numerous Lewy bodies in neurons of
      the subcoeruleus nucleus, a region that is involved in REM sleep control.
      CONCLUSION: The visual hallucinations that coincide with daytime episodes of REM
      sleep in patients who also experience post-REM delusions at night may be dream
      imagery. Psychosis in patients with PD may therefore reflect a narcolepsy-like
      REM sleep disorder.

PMID- 10908907
TI  - Arteriovenous fistula in neurofibromatosis.

PMID- 10908908
TI  - The shorthand publications of Sir William Richard Gowers.
AB  - OBJECTIVE: To examine the shorthand publications of Sir William Richard Gowers.
      BACKGROUND: Gowers developed an almost obsessional interest in Pitman shorthand.
      During the later part of his active career (1894-1910), the bulk of his
      professional writing, comprising nearly 100 articles, was printed entirely in
      Pitman shorthand in the Phonographic Record of Clinical Teaching and Medical
      Science. The obscurity and rarity of this periodical, and the increasingly arcane
      nature of Pitman shorthand, has left the bulk of these articles "buried in
      obscurity and locked up in code" (M. Critchley, 1949). DESIGN/METHODS: A complete
      set of Gowers' shorthand publications as listed in his standard bibliography was
      compiled. Transcription of the Pitman shorthand outlines was performed by a
      qualified Pitman shorthand transcriber and verified using the contemporaneous
      Phonographic Outlines of Medical Terms (1902) as an authoritative guide. RESULTS:
      The first transcription of Gowers' shorthand publications has now been completed.
      The history of Gowers' interest in shorthand and his efforts to proselytize the
      medical profession is reviewed. Selected excerpts are presented from his
      shorthand articles, which include papers devoted to problems in practical
      diagnosis, notes on clinical teaching, and the shorthand transcriptions of his
      lectures at Queen Square and at University College Hospital on such diverse
      subjects as myelitis, neurosyphilis, polio, muscular dystrophy, tumors, vascular
      disease, epilepsy, and the nervous system in old age. CONCLUSIONS: The previously
      unpublished transcriptions of his shorthand articles represent a major and
      previously inaccessible part of Gowers' neurologic opus. These articles exemplify
      Gowers as a practicing neurologist and teacher, and significantly expand our
      insights into one of neurology's most significant and influential figures.

PMID- 10908909
TI  - Striatal serotonin is depleted in brain of a human MDMA (Ecstasy) user.
AB  - The authors found that striatal levels of serotonin and those of its metabolite 5
      hydroxyindoleacetic acid were severely depleted by 50 to 80% in brain of a
      chronic user of methylenedioxymethamphetamine (MDMA) whereas concentrations of
      dopamine were within the normal control range. Our data suggest that MDMA
      exposure in the human can cause decreased tissue stores of serotonin and
      therefore some of the behavioral effects of this drug of abuse could be caused by
      massive release and depletion of brain serotonin.

PMID- 10908910
TI  - Disease progression in sporadic inclusion body myositis: observations in 78
      patients.
AB  - Functional decline for each decade at symptom onset and need for cane, walker, or
      wheelchair were assessed in 78 biopsy-proved patients with sporadic inclusion
      body myositis. Patients with disease onset between 40 and 59 years used a walker
      after 10.2 +/- 5.8 years, whereas those with disease onset between 60 and 79
      years used a walker after 5.7 +/- 5.0 years (p = 0.05). Because patients progress
      faster to disability when symptoms begin after the age of 60, age at disease
      onset may define patient subsets for stratification in clinical trials.

PMID- 10908911
TI  - Poliomyelitic-like illness in central European encephalitis.
AB  - Central European encephalitis (CEE) may be accompanied by myeloradiculitic
      symptoms in up to 5% of patients. The authors report six patients with a myelitic
      form of CEE mimicking acute poliomyelitis with bulbar and arm predominance and a
      poor prognosis. Three patients died. Of the survivors, only one can perform most
      activities of daily living, but still needs assisted ventilation at night.
      Autopsy in one patient showed severe cervicothoracic inflammation with changes
      almost exclusively in anterior horn cells and roots, as typically seen in
      poliomyelitis.

PMID- 10908912
TI  - Mitochondrial DNA haplogroups and susceptibility to AD and dementia with Lewy
      bodies.
AB  - The authors analyzed the relationship between nuclear genetic risk factors
      (apolipoprotein E genotype) and mitochondrial DNA (mtDNA) sequence variants in
      pathologically proved cases of AD (n = 185), dementia with Lewy bodies (DLB; n =
      84), and control subjects (n = 179). Specific European mtDNA haplogroups and the
      A4336G mutation were not associated with an increased risk of AD. mtDNA
      haplogroup H was overrepresented in the DLB patients when compared with control
      subjects. Additional studies are needed to clarify the significance of the
      association.

PMID- 10908913
TI  - Spinal manifestations of vertebral artery dissection.
AB  - Among 111 patients with vertebral artery dissection (VAD), two presented with
      spinal manifestations: one with a C5-C6 radiculopathy and the other with a
      cervical myelopathy. Of 13 previously reported cases of spinal manifestations of
      VAD (mean age 37 years), ischemic cervical myelopathy was noted in seven;
      cervical radiculopathy, often at C5-C6 and primarily motor, in five; and
      hemorrhagic complications in one, with chest pain being part of the presentation.

PMID- 10908914
TI  - Small, unruptured intracranial aneurysms and management of symptomatic carotid
      artery stenosis. North American Symptomatic Carotid Endarterectomy Trial Group.
AB  - Of the 2885 patients participating in the North American Symptomatic Carotid
      Endarterectomy Trial, 90 (3.1%) had unruptured intracranial aneurysms (UIA), of
      which 96% had a diameter of less than 10 mm. During an average 5-year follow-up,
      only one patient had subarachnoid hemorrhage 6 days after carotid endarterectomy
      (CE). For patients with unrepaired UIA, the 5-year stroke risk was 10% after CE
      and 22.7% with best medical care. Both risks are similar to those of patients
      without UIA. The decision regarding CE probably should not be influenced by the
      presence of a small UIA.

PMID- 10908915
TI  - Glutamate decarboxylase is not genetically linked to pyridoxine-dependent
      seizures.
AB  - Several aspects of pyridoxine-dependent seizure (PDS) suggest a mutation
      affecting glutamate decarboxylase (GAD) as a possible cause. To examine the
      possibility of GAD linkage with PDS, the authors performed genotype analyses of
      three families using polymorphic markers near the GAD genes (GAD1 and GAD2). In
      each family, the affected siblings exhibited different genotypes for the GAD2
      gene; in two families the GAD1 genotype was disparate. These findings suggest
      that a mutation of GAD is not directly involved in all cases of PDS.

PMID- 10908916
TI  - Optical intrinsic signal imaging in a rodent seizure model.
AB  - The authors studied seizure activity with optical intrinsic signal (OIS) imaging
      in a rat seizure model. OIS, which measures vascular and metabolic effects
      associated with neuronal activity, showed significant cortical reflectance
      changes from penicillin-induced seizures, and correlated well with EEG
      epileptiform discharges. Furthermore, OIS changes often preceded initial EEG
      spikes. These observations suggest that OIS is well coupled with seizure
      activity, and may provide sensitive cues for seizure detection.

PMID- 10908917
TI  - The fogging effect.

PMID- 10908918
TI  - Responsiveness to celecoxib in chronic paroxysmal hemicrania.

PMID- 10908919
TI  - Acute myelopathy following intranasal insufflation of heroin: a case report.

PMID- 10908920
TI  - Recurrent brain hematomas in MELAS associated with an ND5 gene mitochondrial
      mutation.

PMID- 10908921
TI  - Familial neuromyelitis optica (Devic's syndrome) with late onset in Japan.

PMID- 10908922
TI  - Cauda equina syndrome from intradiscal electrothermal therapy.

PMID- 10908923
TI  - A medullary syndrome characterized by wild arm ataxia.

PMID- 10908924
TI  - Isolated trochlear nerve palsy in patients with multiple sclerosis.

PMID- 10908925
TI  - Effect of interferon beta on human myelin basic protein-specific T-cell lines:
      comparison of IFNbeta-1a and IFNbeta-1b.

PMID- 10908926
TI  - Elevated CSF prostaglandin E2 levels in patients with probable AD.

PMID- 10908927
TI  - Cerebellar seizures of Hughlings Jackson.

PMID- 10908928
TI  - Effects of very high antibiotic concentrations on human intervertebral disc cell
      proliferation, viability, and metabolism in vitro.
AB  - STUDY DESIGN: Four antibiotics commonly used during spinal surgery (cefazolin,
      gentamycin, cefamandole, and vancomycin) were tested for their effects on
      cultured human disc cells from the anulus. OBJECTIVE: To determine the viability,
      proliferation, and metabolism of cells cultured from the human anulus after they
      were exposed to four antibiotics. SUMMARY OF BACKGROUND DATA: Previous studies
      concerning the effect of antibiotics on the disc have used animal models or
      explanted discs, but little is understood about the effect of antibiotics on the
      proliferation, viability, and metabolism of cells from the anulus. METHODS: In
      this study, 3H-thymidine incorporation, trypan blue exclusion, and cell
      metabolism were determined using cells from the human anulus grown in monolayer
      culture. The latter measurement used a cytosensor microphysiometer to monitor the
      rate at which cells acidified their microenvironment, an event that is
      proportional to cellular metabolism because it reflects the excretion over time
      of acidic products such as lactic acid from glycolysis and CO2 from cellular
      respiration. RESULTS: After 48 hours of antibiotic exposure, cell viability was
      significantly lower as a result of all four antibiotics at the highest
      concentration tested. Cell proliferation was lower after exposure to cefazolin
      and cefamandole. During a 6-hour antibiotic exposure, anulus cells in the highest
      concentration of cefamandole or vancomycin displayed a significantly decreased
      rate of cell metabolism. CONCLUSIONS: These findings show that high doses of
      antibiotics can have direct, deleterious effects on cultured disc cell survival,
      cell proliferation, and metabolic rates. Discitis is a serious primary or
      postoperative complication that often requires prolonged antibiotic treatment.
      Studies such as the current investigation with cultured cells from the anulus
      show the importance of a greater understanding concerning antibiotic effects on
      disc cell proliferation and metabolism.

PMID- 10908929
TI  - Effects of core body temperature on changes in spinal somatosensory-evoked
      potential in acute spinal cord compression injury: an experimental study in the
      rat.
AB  - STUDY DESIGN: Acute spinal cord injury was induced by a clip compression model in
      rats to approximate spinal cord injury encountered in spinal surgery. Spinal
      somatosensory-evoked potential neuromonitoring was used to study the
      electrophysiologic change. OBJECTIVES: To compare and correlate changes in evoked
      potential after acute compression at different core temperatures with
      postoperative neurologic function and histologic change, to evaluate current
      intraoperative neuromonitoring warning criteria for neural damage, and to confirm
      the protective effect of hypothermia in acute spinal cord compression injury by
      electrophysiologic, histologic, and clinical observation. SUMMARY OF BACKGROUND
      DATA: With the increase in aggressive correction of spinal deformities, and the
      invasiveness of surgical instruments, the incidence of neurologic complication
      appears to have increased despite the availability of sensitive intraoperative
      neuromonitoring techniques designed to alert surgeons to impending neural damage.
      Many reasons have been given for the frequent failures of neuromonitoring, but
      the influence of temperature-a very important and frequently encountered factor
      on evoked potential has not been well documented. Specifically, decrease in
      amplitude and elongation of latency seem not to have been sufficiently taken into
      account when intraoperative neuromonitoring levels were interpreted and when
      acceptable intraoperative warning criteria were determined. METHODS: Experimental
      acute spinal cord injury was induced in rats by clip compression for two
      different intervals and at three different core temperatures. Spinal
      somatosensory-evoked potential, elicited by stimulating the median nerve and
      recorded from the cervical interspinous C2-C3, was monitored immediately before
      and after compression, and at 15-minute intervals for 1 hour. RESULTS: Spinal
      somatosensory-evoked potential change is almost parallel to temperature-based
      amplitude reduction and latency elongation. Significant neurologic damage induced
      by acute compression of the cervical spinal cord produced a degree of effect on
      the amplitude of spinal somatosensory-evoked potential in normothermic conditions
      that differed from the effect in moderately hypothermic conditions. Using the
      same electromonitoring criteria,moderately hypothermic groups showed a
      significantly higher false-negative rate statistically (35%) than normothermic
      groups (10%). CONCLUSIONS: Systemic cooling may protect against the detrimental
      effects of aggressive spinal surgical procedures. There is still not enough
      published information available to establish statistically and ethically
      acceptable intraoperative neuromonitoring warning and intervention criteria
      conclusively. Therefore, an urgent need exists for further investigation.
      Although a reduction of more than 50% in evoked potential still seems acceptable
      as an indicator of impending neural function loss, maintenance of more than 50%
      of baseline evoked potential is no guarantee of normal postoperative neural
      function, especially at lower than normal temperatures.

PMID- 10908930
TI  - Effect of electrical stimulation of peripheral nerves on neuropathic pain.
AB  - STUDY DESIGN: Changes in the electrophysiologic response of spinal dorsal horn
      neurons elicited by peripheral electrical stimulation were examined. OBJECTIVE:
      To investigate whether the electrical stimulation of peripheral nerves causes an
      inhibition of pain at the spinal cord level. SUMMARY OF BACKGROUND DATA: The wide
      dynamic range neurons studied were known to be excited by primary afferent
      fibers, not only combined A (delta) and C nociceptive fibers, but also low
      threshold mechanoreceptive A (beta) fibers and A (delta) fibers of down hairs.
      The wide dynamic range neurons are classified as nociceptive neurons. METHODS:
      Responses of wide dynamic range neurons in the lumbosacral dorsal horn to input
      from C fibers were studied in urethane chloralose-anesthetized cats. The
      posterior tibial nerve and sciatic nerve were stimulated simultaneously to
      examine the effect on the C fiber responses elicited by superficial peroneal
      nerve stimulation. RESULTS: Simultaneous stimulation of the posterior tibial
      nerve and sciatic nerve was performed with superficial peroneal nerve C fiber
      stimulation. CONCLUSIONS: This study demonstrated that electrical stimulation of
      peripheral nerves leads to inhibitory input to the pain pathways at the spinal
      cord level.

PMID- 10908931
TI  - Torsional rigidity of scoliosis constructs.
AB  - STUDY DESIGN: A biomechanical study of the rigidity of various scoliosis
      constructs instrumented with and without caudal pedicle screw anchors and with
      none, one, or two cross-link devices. OBJECTIVES: To determine whether the
      increased torsional rigidity provided by distal pedicle screw fixation might make
      cross-linking unnecessary. SUMMARY OF BACKGROUND DATA: Pedicle screws and cross
      linking devices have been shown to increase the structural rigidity of spinal
      constructs. Their relative contributions to scoliosis construct rigidity has not
      been determined. METHODS: "Short" (T2-T11) and "long" (T2-L3) scoliosis
      constructs were mounted on an industrially fabricated spine model and tested in a
      hydraulic testing machine. Four different short and four different long
      constructs were tested: hooks only, hooks with concave side thoracic sublaminar
      wires, hooks with distal pedicle screw anchors, and hooks, distal pedicle screw
      anchors, and concave thoracic sublaminar wires. There were four iterations for
      each construct tested: no cross-links, one superior cross-link at T4-T5, one
      inferior cross-link at T9-T10, and two cross-links. Torsional rigidity was tested
      by applying a rotational torque at T2. Vertebral body motion was recorded with a
      three-dimensional video analysis system. RESULTS: Constructs with distal pedicle
      screws were statistically more rigid in torsion than those with hooks as distal
      anchors. The additional torsional rigidity from one or more cross-links was
      negligible compared with that provided by pedicle screws. CONCLUSIONS: With
      pedicle screws as distal anchors in scoliosis constructs, cross-linking with one
      or two devices adds very little additional rotational stiffness and may be
      unnecessary in many cases.

PMID- 10908932
TI  - Segmental stability and compressive strength of posterior lumbar interbody fusion
      implants.
AB  - STUDY DESIGN: Human cadaveric study on initial segmental stability and
      compressive strength of posterior lumbar interbody fusion implants. OBJECTIVES:
      To compare the initial segmental stability and compressive strength of a
      posterior lumbar interbody fusion construct using a new cortical bone spacer
      machined from allograft to that of titanium threaded and nonthreaded posterior
      lumbar interbody fusion cages, tested as stand-alone and with supplemental
      pedicle screw fixation. SUMMARY OF BACKGROUND DATA: Cages were introduced to
      overcome the limitations of conventional allografts. Radiodense cage materials
      impede radiographic assessment of the fusion, however, and may cause stress
      shielding of the graft. METHODS: Multisegmental specimens were tested intact,
      with posterior lumbar interbody fusion implants inserted into the L4/L5 interbody
      space and with supplemental pedicle screw fixation. Three posterior lumbar
      interbody fusion implant constructs (Ray Threaded Fusion Cage, Contact Fusion
      Cage, and PLIF Allograft Spacer) were tested nondestructively in axial rotation,
      flexion-extension, and lateral bending. The implant-specimen constructs then were
      isolated and compressed to failure. Changes in the neutral zone, range of motion,
      yield strength, and ultimate compressive strength were analyzed. RESULTS: None of
      the stand-alone implant constructs reduced the neutral zone. Supplemental pedicle
      screw fixation decreased the neutral zone in flexion-extension and lateral
      bending. Stand-alone implant constructs decreased the range of motion in flexion
      and lateral bending. Differences in the range of motion between stand-alone cage
      constructs were found in flexion and extension (marginally significant).
      Supplemental posterior fixation further decreased the range of motion in all
      loading directions with no differences between implant constructs. The Contact
      Fusion Cage and PLIF Allograft Spacer constructs had a higher ultimate
      compressive strength than the Ray Threaded Fusion Cage. CONCLUSIONS: The
      biomechanical data did not suggest any implant construct to behave superiorly
      either as a stand-alone or with supplemental posterior fixation. The PLIF
      Allograph Spacer is biomechanically equivalent to titanium cages but is devoid of
      the deficiencies associated with other cage technologies. Therefore, the PLIF
      Allograft Spacer is a valid alternative to conventional cages.

PMID- 10908933
TI  - Rigid fusion after cloward operation for cervical disc disease using autograft,
      allograft, or xenograft: a randomized study with radiostereometric and clinical
      follow-up assessment.
AB  - STUDY DESIGN: In this study, 43 patients scheduled for a single-level cervical
      Cloward procedure for disc disease were randomized prospectively to fusion with
      autograft, allograft, or xenograft. OBJECTIVE: To outline any differences in
      fusion over time in terms of final mobility and clinical outcome between the
      three bone grafts. SUMMARY OF BACKGROUND DATA: Fusion is used to relieve pain
      from a spinal segment. The bovine xenograft gives a fibrous fusion in contrast to
      the solid bone fusion obtained with autograft from the iliac crest, but no
      definite differences in clinical outcome have been shown previously after surgery
      at a single level. METHODS: By use of radiostereometric analysis, 33 patients
      were observed after 6, 12, and 24 to 50 (mean, 37) months. All 43 patients
      underwent clinical examination, which involved pain rating before and after
      surgery, with a final follow-up assessment by an unbiased observer. RESULTS:
      Mobility could be demonstrated in 9 patients after 1 year and in 6 patients at
      the final follow-up assessment, without pain, and with no difference between bone
      grafts. The patients who received autograft experienced a greater reduction of
      pain than the patients treated with xenograft. CONCLUSIONS: Most of the patients
      healed with a rigid fusion no matter which graft was used, but the healing
      process took longer than expected. The clinical results were not influenced by
      whether mobility could be demonstrated. There was a tendency toward better
      clinical results in the patients treated with autograft.

PMID- 10908934
TI  - A prospective study of serum pseudocholinesterase levels in patients with chronic
      spinal pain: a preliminary study.
AB  - STUDY DESIGN: One-dimensional polyacrylamide gel electrophoresis was used to
      study serum esterase enzymatic activity in three groups of patients and one group
      of normal volunteers. OBJECTIVES: To determine whether there is a statistically
      significant correlation between variations of serum pseudocholinesterase and the
      perception of pain in patients with chronic spinal pain. SUMMARY OF BACKGROUND
      DATA: Changes in levels of cholinesterase in the extracellular space of the brain
      and in the cerebral spinal fluid have been found to be associated in animal pain
      experimentation. METHODS: Ninety-three surgical patients with chronic spinal
      pain, six surgical control subjects operated for conditions not associated with
      pain, 21 normal control volunteers, and nine disabled patients receiving monetary
      benefits were studied. The patients were analyzed for a period of time by rating
      the perception of their pain with a visual assessment score at the time venous
      blood was drawn. Serum samples were prepared, serum pseudocholinesterase was
      monitored, separated, and quantified according to Allen et al.5 Paired sample t
      tests were used to statistically evaluate the data. RESULTS: A trend of
      correlation was noted between preoperative serum pseudocholinesterase levels and
      visual assessment score: serum pseudocholinesterase levels increased as visual
      assessment score increased. The mean preoperative serum pseudocholinesterase
      level of chronic spinal pain patients (1313; SE = 26), which was significantly
      higher than the mean levels of the normal control volunteers (941; SE = 24;
      P<0.001) and that of surgical control subjects (1018; SE = 63; P <0.01),
      decreased significantly with anesthesia (P<0.005). The mean preoperative serum
      pseudocholinesterase level of the surgical controls, however, remained unchanged
      with anesthesia. A correlation demonstrated between visual assessment score and
      serum pseudocholinesterase in chronic spinal pain patients was not observed in
      six of nine patients receiving disability payments for more than a year.
      CONCLUSIONS: Measurements of quantitative alterations of serum
      pseudocholinesterase levels may be useful in the treatment of patients with
      chronic spinal pain.

PMID- 10908935
TI  - The use of nonorganic signs and symptoms as a screening tool for return-to-work
      in patients with acute low back pain.
AB  - STUDY DESIGN: A longitudinal cohort study of patients with acute, work-related
      low back pain undergoing physical therapy treatment. OBJECTIVE: To determine cut
      off values maximizing the predictive ability of the nonorganic signs and symptoms
      in patients with acute, work-related low back pain and to calculate the
      predictive validity of the signs and symptoms, alone and in combination, using an
      outcome of return to work within 4 weeks of initiating treatment. SUMMARY OF
      BACKGROUND DATA: Waddell et al have proposed nonorganic signs and symptoms as
      screening tools in patients with chronic low back pain for detecting the presence
      of abnormal illness behavior and identifying patients in need of further
      evaluation to improve the likelihood of a successful treatment outcome. METHODS:
      Consecutive patients referred to physical therapy with work-related low back pain
      of less than 2 weeks' duration were examined for the presence of nonorganic signs
      and symptoms before initiating physical therapy treatment. The outcome measure
      used was the ability to return to work without restrictions within 4 weeks of the
      initial evaluation. RESULTS: Sensitivity, specificity, and likelihood ratios were
      calculated for all possible cut-off values for the nonorganic signs, symptoms,
      and the nonorganic index (signs and symptoms). The best cut-off values were two
      or more signs (negative likelihood ratio = 0.75), three or more symptoms
      (negative likelihood ratio = 0.62), and an index score of three or more (negative
      likelihood ratio = 0.59). Area under a receiver operator characteristic curve for
      the signs, symptoms, and index were 0.60, 0.63, and 0.63, respectively.
      CONCLUSIONS: Because the nonorganic tests are purported to serve as screening
      tests, cut-off values were selected that minimized false-negative results. Even
      with optimal cut-off values, none of the nonorganic tests served as effective
      screening tools. Other screening tools may prove more effective for the early
      identification of patients at increased risk for delay in returning to work after
      an episode of acute low back pain.

PMID- 10908936
TI  - Cineradiographic motion analysis of normal lumbar spine during forward and
      backward flexion.
AB  - STUDY DESIGN: Motion characteristics of the lumbar spine in the sagittal plane
      were investigated in vivo using cineradiography. OBJECTIVES: To evaluate the
      differences in motion characteristics of the normal lumbar spine between forward
      and backward flexion. SUMMARY OF BACKGROUND DATA: Despite previous lumbar
      kinematic studies, differences in motion characteristics of the lumbar spine
      between forward and backward flexion remain unclear. METHODS: Cineradiographic
      motion analysis was performed in 10 asymptomatic healthy male volunteers for two
      different lumbar motions. The motions consisted of active forward flexion (from
      maximum extension to maximum flexion) and active backward flexion (from maximum
      flexion to maximum extension). Displacements of the anterior and posterior
      vertebral corners from L3/L4 to L5/S1 were measured continuously in reference to
      the local coordinate system. Parameters investigated were onset of segmental
      motion, velocity of segmental motion, and continuous motion profiles of the
      vertebral corners during the two different motions. RESULTS: During forward
      flexion, initial lumbar motion started stepwise from the upper level (L3/L4) to
      the lower levels with phase lags. Angular velocity at the onset of motion
      increased as the level descended. On the contrary, during backward flexion,
      initial motion started from the lower level (L5/S1) to the upper levels. There
      was no relation between velocity and spinal levels during backward flexion.
      Motion profiles of both anterior and posterior vertebral corners at L3/L4 and
      L4/L5 segments during forward flexion were similar to those during backward
      flexion. However, the motion profiles at L5/S1 segment during forward flexion
      were different from those during backward flexion. CONCLUSIONS: During forward
      flexion of the lumbar spine, initial motion started from upper segments to the
      lower segments with phase lags. During backward flexion, initial motion started
      from the lower segments to the upper segments. Motion profiles of the vertebral
      corners during forward flexion were similar to those during backward flexion at
      L3/L4 and L4/L5. The motion profiles at L5/S1 were different between both
      flexions.

PMID- 10908937
TI  - Cervical muscle dysfunction in the chronic whiplash associated disorder grade II
      (WAD-II).
AB  - STUDY DESIGN: In a cross-sectional study, surface electromyography measurements
      of the upper trapezius muscles were obtained during different functional tasks in
      patients with a chronic whiplash associated disorder Grade II and healthy control
      subjects. OBJECTIVES: To investigate whether muscle dysfunction of the upper
      trapezius muscles, as assessed by surface electromyography, can be used to
      distinguish patients with whiplash associated disorder Grade II from healthy
      control subjects. SUMMARY OF BACKGROUND INFORMATION: In the whiplash associated
      disorder, there is need to improve the diagnostic tools. Whiplash associated
      disorder Grade II is characterized by the presence of "musculoskeletal signs."
      Surface electromyography to assess these musculoskeletal signs objectively may be
      a useful tool. METHODS: Normalized smoothed rectified electromyography levels of
      the upper trapezius muscles of patients with whiplash associated disorder Grade
      II (n = 18) and healthy control subjects (n = 19) were compared during three
      static postures, during a unilateral dynamic manual exercise, and during
      relaxation after the manual exercise. Coefficients of variation were computed to
      identify the measurement condition that discriminated best between the two
      groups. RESULTS: The most pronounced differences between patients with whiplash
      associated disorder Grade II and healthy control subjects were found particularly
      in situations in which the biomechanical load was low. Patients showed higher
      coactivation levels during physical exercise and a decreased ability to relax
      muscles after physical exercise. CONCLUSIONS: Patients with whiplash associated
      disorder Grade II can be distinguished from healthy control subjects according to
      the presence of cervical muscle dysfunction, as assessed by surface
      electromyography of the upper trapezius muscles. Particularly the decreased
      ability to relax the trapezius muscles seems to be a promising feature to
      identify patients with whiplash associated disorder Grade II. Assessment of the
      muscle (dys)function by surface electromyography offers a refinement of the
      whiplash associated disorder classification and provides an indication to a
      suitable therapeutic approach.

PMID- 10908938
TI  - Comparison of single- and dual-rod techniques for posterior spinal
      instrumentation in the treatment of adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Two groups of patients undergoing posterior spinal instrumentation
      and arthrodesis for treatment of adolescent idiopathic scoliosis were reviewed
      retrospectively. OBJECTIVE: To compare intraoperative concerns (operative time
      and blood loss), complications, and outcome in patients undergoing single or
      double posterior rod instrumentation for treatment of adolescent idiopathic
      scoliosis. SUMMARY OF BACKGROUND DATA: The current treatment of idiopathic
      scoliosis includes posterior spinal instrumentation and arthrodesis. The standard
      configuration is a rectangular construct of dual rods connected by cross-links.
      Use of a single rod with multiple fixation points has been proposed as an
      alternative method to decrease operative time and blood loss, and to avoid late
      deep infections. METHODS: In this study, 21 patients underwent posterior
      instrumentation using a standard dual-rod construct, and 25 patients underwent
      posterior instrumentation using a solitary rod with multiple fixation points.
      Patients were assessed after a minimum 2-year follow-up period. RESULTS: No
      significant differences were found in blood loss, operative time, or overall
      frequency of long-term complications. Although not statistically significant, the
      trend was toward implant prominence in the double-rod group and implant failure
      in the single-rod group. Implant failure occurred only in instrumentations
      extending into the lumbar spine. There was no statistical difference in curve
      progression. CONCLUSIONS: Single-rod instrumentation and dual-rod constructs
      offered similar curve correction, blood loss, and operative time. However, single
      rod instrumentation may be more prone to implant failure when extended into the
      lumbar spine.

PMID- 10908939
TI  - Longitudinal quantitative measures of the natural course of low back pain
      recovery.
AB  - STUDY DESIGN: A prospective study was developed to quantify acute low back pain
      recovery. OBJECTIVE: To compare traditional self-report measures of low back pain
      recovery with a quantitative measure of recovery. SUMMARY OF BACKGROUND DATA: The
      magnitude of low back disorders in society continues to be a problem. To prevent
      secondary injuries, an understanding of recovery must be gained by comparing the
      natural course of recovery using several outcome measures. METHODS: For this
      study, 16 occupational and 16 nonoccupational patients with low back pain were
      recruited. Recovery was monitored prospectively every 2 weeks for 3 to 6 months,
      using subjective work status, pain symptoms, activities of daily living, and
      objective functional performance probability (trunk kinematics). RESULTS: Return
      to work underestimated the percentage of subjects impaired, as compared with all
      other outcome measures. Symptoms, activities of daily living, and functional
      performance probability all showed similar patterns of recovery for 0 to 12
      weeks. At 14 weeks, there was a lag in functional performance recovery. Both
      symptoms and activities of daily living indicated that 80% of the population was
      recovered, whereas functional performance indicated the figure to be 68%.
      CONCLUSION: This prospective study demonstrates the natural course of recovery
      using several outcome measures. The objective kinematic functional performance
      measure of recovery quantifies a different aspect of impairment not evaluated by
      traditional subjective measures. Use of several outcome measures may lead to a
      better understanding of low back pain recovery or residual impairment, which may
      minimize the risk of recurrent injury.

PMID- 10908940
TI  - Decrease in trunk muscular response to perturbation with preactivation of lumbar
      spinal musculature.
AB  - STUDY DESIGN: An experimental study of healthy subjects' trunk muscle responses
      to force perturbations at differing angles and steady state efforts. OBJECTIVES:
      To determine whether increased preactivation of muscles was associated with
      decreased likelihood of muscular activation in response to a transient force
      perturbation. SUMMARY OF BACKGROUND DATA: Trunk stability (ability to return to
      equilibrium position after a perturbation) requires the stiffness of
      appropriately activated muscles to prevent buckling and consequent "self-injury."
      Therefore, greater trunk muscle preactivation might decrease the likelihood of
      reflex muscle responses to small perturbations. METHODS: Each of 13 subjects
      stood in an apparatus with the pelvis immobilized. A harness around the thorax
      provided a preload and a force perturbation by a horizontal cable and a movable
      pulley attached to one of five anchorage points on a wall track surrounding the
      subject at angles of 0 degrees, 45 degrees, 90 degrees, 135 degrees, and 180
      degrees to the forward direction. Subjects first equilibrated with a preload
      effort of nominally 20% or 40% of their maximum extension effort. Then a single
      full sine-wave force perturbation pulse of nominal amplitude, 7.5% or 15% of
      maximum effort, duration 80 milliseconds or 300 milliseconds, was applied at a
      random time, with three repeated trials of each test condition. The applied force
      (via a load cell) and the electromyographic activity of six right and left pairs
      of trunk muscles were recorded. Muscle responses were detected by two methods. 1)
      Shewhart method: electromyographic signal greater than "baseline" values by more
      than three standard deviations, and 2) Mean Electromyographic Difference method:
      mean electromyographic signal in a time window 25 to 150 milliseconds after the
      force perturbation greater than that in a 25- to 150-millisecond window before
      the perturbation. RESULTS: Lower preload efforts were associated with more muscle
      responses (overall mean response detection rate = 33% at low preload and 25% at
      high preload). Using the Shewhart method, there were significant differences by
      effort (P<0.05) for all abdominal muscles and for all left dorsal muscles except
      multifidus. Using the Mean Electromyographic Difference method, there were
      significant differences by effort (P<0.05) for the same dorsal muscles, but only
      for one of the abdominal muscles. CONCLUSIONS: Findings are consistent with the
      hypothesis that the spine can be stabilized by the stiffness of activated
      muscles, obviating the need for active muscle responses to perturbations.

PMID- 10908941
TI  - Access to pedestrian roads, daily activities, and physical performance of
      adolescents.
AB  - STUDY DESIGN: A cross-sectional study using a questionnaire and physical tests
      was performed. OBJECTIVE: To study how access to pedestrian roads and daily
      activities are related to low back strength, low back mobility, and hip mobility
      in adolescents. SUMMARY OF BACKGROUND DATA: Although many authorities express
      concern about the passive lifestyle of adolescents, little is known about
      associations between daily activities and physical performance. METHODS: This
      study compared 38 youths in a community lacking access to pedestrian roads with
      50 youths in nearby area providing excellent access to pedestrian roads. A
      standardized questionnaire was used to obtain data about pedestrian roads, school
      journeys, and activities from the local authorities and the pupils. Low back
      strength was tested as static endurance strength, low back mobility by modified
      Schober techniques, and hip mobility by goniometer. For statistical analyses, a P
      value of 0.05 or less determined significance. RESULTS: In the area using school
      buses, the pupils had less low back extension, less hamstring flexibility, and
      less hip abduction, flexion, and extension than pupils in the area with
      pedestrian roads. Multivariate analyses showed no associations between walking or
      bicycling to school and anatomic function, but regular walking or bicycling to
      leisure-time activities associated positively with low back strength, low back
      extension, hip flexion, and extension. Distance by school bus associated
      negatively with hip abduction, hip flexion, hip extension, and hamstring
      flexibility (P<0.001). Time spent on television or computer associated negatively
      but insignificantly with low back strength, hamstring flexibility, hip abduction,
      and flexion (P<0.1). CONCLUSION: The results indicate that access to pedestrian
      roads and other lifestyle factors are associated with physical performance.

PMID- 10908942
TI  - Does early intervention with a light mobilization program reduce long-term sick
      leave for low back pain?
AB  - STUDY DESIGN: A controlled randomized clinical trial was performed. OBJECTIVE: To
      investigate the effect of a light mobilization program on the duration of sick
      leave for patients with subacute low back pain. SUMMARY OF BACKGROUND DATA: Early
      intervention with information, diagnostics, and light mobilization may be a cost
      effective method for returning patients quickly to normal activity. In this
      experiment, patients were referred to a low back pain clinic and given this
      simple and systematic program as an outpatient treatment. METHODS: In this study,
      457 patients sick-listed 8 to 12 weeks for low back pain, as recorded by the
      National Insurance Offices, were randomized into two groups: an intervention
      group (n = 237) and a control group (n = 220). The intervention group was
      examined at a spine clinic and given information and advice to stay active. The
      control group was not examined at the clinic, but was treated with conventional
      primary health care. RESULTS: At 12-month follow-up assessment, 68.4% in the
      intervention group had returned to full-duty work, as compared with 56.4% in the
      control group. CONCLUSIONS: Early intervention with examination, information, and
      recommendations to stay active showed significant effects in reducing sick leave
      for patients with low back pain.

PMID- 10908943
TI  - Reduction and fixation of sacroiliac joint dislocation by the combined use of S1
      pedicle screws and the galveston technique.
AB  - STUDY DESIGN: This retrospective study was designed to analyze the results of the
      treatment with S1 pedicle screws and the Galveston technique of seven patients
      with sacroiliac dislocation. OBJECTIVES: To evaluate the effectiveness of the
      combined use of S1 pedicle screws and the Galveston technique for the treatment
      of sacroiliac dislocation. SUMMARY OF BACKGROUND DATA: Although several
      procedures for internal fixation of sacroiliac dislocation have been reported,
      there have been no reports discussing surgical treatment of sacroiliac
      dislocation by the combined use of S1 pedicle screws and the Galveston technique.
      METHODS: Seven patients with sacroiliac dislocation were treated with pedicle
      screws of S1 and iliac rod according to the Galveston technique. In the seven
      patients, the dislocation was associated with vertical displacement of the
      sacroiliac joint and rotational deformity of the pelvic ring. They were
      classified into Type-C pelvic disruption according to the Tile's classification.
      Three patients with disruption of the symphysis pubis underwent additional
      fixation of the symphysis using a dynamic compression plate. The remaining four
      patients were treated by the posterior procedure alone. RESULTS: The vertical
      displacement was completely reduced in five patients, and the rotational
      deformity was completely corrected in four patients. The reduction was maintained
      at the time of the final follow-up evaluation. There were no perioperative
      complications with the exception of late infection in one patient. CONCLUSIONS:
      The combined use of S1 pedicle screws and the Galveston technique provided
      immediate stability and sufficient reduction for sacroiliac dislocation in seven
      patients in this study. This hybrid internal fixation procedure is useful for
      reduction and fixation of sacroiliac dislocation associated with the vertical and
      rotational instability of the pelvic ring.

PMID- 10908944
TI  - Idiopathic spinal cord herniation: report of three cases and review of the
      literature.
AB  - STUDY DESIGN: Three case reports and a literature review are presented.
      OBJECTIVE: To describe characteristic clinical and radiographic findings of
      idiopathic spinal cord herniation. SUMMARY OF BACKGROUND DATA: Idiopathic spinal
      cord herniation is a rare disease, with only 26 cases reported before the current
      study. METHODS: Three cases of idiopathic spinal cord herniation are reported,
      and previous reports on this subject are reviewed. RESULTS: The responsible
      regions were in the thoracic spine from T2 to T7. Symptoms were mainly unilateral
      muscle atrophy in the lower extremity and sensory disturbance below the thoracic
      level. These symptoms had been progressing gradually. Magnetic resonance imaging
      demonstrated a unique feature: The spinal cord shifted anteriorly in a few
      segments. Computed tomographic myelogram showed another distinctive picture:
      There was no subarachnoid space anterior to the spinal cord. CONCLUSIONS: Because
      idiopathic spinal cord herniation is out of the concept of "compression
      myelopathy," this condition may be a pitfall in the diagnosis. Idiopathic spinal
      cord herniation should be recognized as one of the treatable causes for thoracic
      myelopathy.

PMID- 10908945
TI  - Vertebral artery anomaly with atraumatic dissection causing thromboembolic
      ischemia: a case report.
AB  - STUDY DESIGN: A case report is presented. OBJECTIVES: To illustrate a rare cause
      of atraumatic vertebral artery dissection resulting from anomalous entry of the
      vessel at the C3 transverse foramen induced by normal physiologic head and neck
      motion, and to review vertebral artery anatomy and mechanisms whereby it is
      vulnerable to pathologic compression. SUMMARY OF BACKGROUND DATA: The vertebral
      artery usually enters the transverse foramen at C6. Rarely, the artery enters at
      C5 or C4. Only one prior case with entry at C3 has been reported. That patient
      experienced recurrent quadriplegia and locked-in syndrome caused by vertebral
      artery obstruction. A 27-year-old woman with a history of classic migraine
      experienced neurologic symptoms on three occasions related to physiologic neck
      and arm movements. Magnetic resonance angiogram was not diagnostic, but standard
      arteriography demonstrated anomalous vertebral artery entry into the C3
      transverse foramen and focal dissection. METHODS: Pertinent literature and the
      patient's history, physical examination, and radiologic studies were reviewed.
      RESULTS: Standard cervico-cerebral arteriogram demonstrated focal dissection at
      C4 and thromboembolic complications in distal vertebral and basilar arteries.
      Initially, diagnosis by magnetic resonance angiogram was elusive. However,
      arteriography allowed prompt diagnosis followed by anticoagulation with
      resolution of neurologic symptoms. CONCLUSIONS: Vertebral artery dissection
      without trauma is rare, but should be considered when neurologic symptoms
      accompany physiologic cervical movements. For cases in which vertebrobasilar
      thromboembolic ischemia is suspected, magnetic resonance angiogram may prove
      inadequate for demonstrating the causative vascular pathology. Therefore,
      standard cervico-cerebral arteriography should be performed.

PMID- 10908946
TI  - Primary intradural extramedullary ependymoma: case report and review of the
      literature.
AB  - STUDY DESIGN: The authors report the ninth case in the literature of a primary
      intradural extramedullary ependymoma of the spinal cord. OBJECTIVE: To discuss
      surgical treatment and the physiopathologic hypothesis of this localization on
      the basis of the results of the present study and a review of the literature.
      SUMMARY OF BACKGROUND DATA: Ependymoma is a glial tumor known to arise in the
      central nervous system. Intradural extramedullary location of this neoplasm has
      been exceptionally described previously. METHODS: A 43-year-old woman was
      admitted to the authors' institution with an history of progressive paraplegia.
      Neurologic examination showed sensory loss below T1 and bladder disturbances.
      Magnetic resonance imaging revealed an enhanced thoracic intradural
      extramedullary tumor, extending from T1-T8. No other lesion in the central
      nervous system was found. Emergency surgical resection was performed. RESULTS:
      Surgery gave confirmation of an encapsulated extramedullary tumor without
      attachment to the spinal cord or to the dura mater. Total removal was achieved
      under microscope. The postoperative course was uneventful, with complete
      neurologic recovery 3 months later. The patient has been well for 24 months of
      follow-up evaluation, without evidence of recurrence on magnetic resonance
      images. Histologic examination revealed the tumor as a benign ependymoma.
      CONCLUSION: The encapsulated feature, the lack of attachment to the central
      nervous system, and the absence of other neoplastic processes within the brain or
      the spinal cord suggested that this lesion is a primary tumor developed from
      ectopic ependymal cells.

PMID- 10908947
TI  - Extraskeletal Ewing's sarcoma: a case report and review of the literature.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To report on the diagnosis and current
      treatment of a rare tumor about the cervical spine. SUMMARY OF BACKGROUND DATA:
      Extraskeletal Ewing's sarcoma (EES) is rare and has not been previously described
      about the cervical spine. We present a case of a 24-year-old man with a large
      mass in the posterior triangle of the neck extending through the vertebral
      foramens of the cervical vertebrae. This was identified as an extraskeletal
      Ewing's sarcoma. Traditional treatment paradigms have been associated with a poor
      prognosis. Since the recommendations of the Intergroup Rhabdomyosarcoma Study II
      study of multimodal chemotherapy and radiotherapy, this tumor has a significantly
      better prognosis. METHOD: Surgical debulking of the tumor was necessary to
      relieve cord compression. Histologic analysis was used to confirm both magnetic
      resonance imaging and computed tomography diagnosis. A chemoradiation therapy
      program was commenced in accordance with Intergroup Rhabdomyosarcoma Study II
      recommendations. RESULTS: Computed tomography and magnetic resonance imaging
      demonstrated a large lobulated mass extending through the exit foramens of C2/C3
      and C3/C4. The mass was entirely extraskeletal and extradural. Histologic
      examination of the excised mass showed microscopy consistent with extraskeletal
      Ewing's sarcoma. After surgical debulking and chemoradiation, the patient made a
      complete recovery. CONCLUSION: A review of the literature confirms that
      extraskeletal Ewing's sarcoma is a rare tumor and particularly so in the region
      of the cervical spine. Early diagnosis and surgical debulking combined with
      current multimodality chemoradiation programs can produce a favorable outcome.

PMID- 10908948
TI  - Imaging corner

PMID- 10908949
TI  - Re: randomized controlled trials in surgery: an essential component of scientific
      progress (Spine 1999; 24:2553-5)

PMID- 10908951
TI  - Imagery

PMID- 10908950
TI  - The role of steroids and their effects on phospholipase A2.

PMID- 10908952
TI  - Alf L. Nachemson, MD, PhD: the first ISSLS-stryker spine lifetime achievement
      award recipient

PMID- 10908954
TI  - [Drugs for 'neglected diseases': a bitter pill].
AB  - Neglected diseases are diseases restricted to poor areas; diseases for which
      there exist no commercial incentives to invest in the development of new
      treatments. Patients suffering from these diseases often have no access to
      essential drugs; this can be a matter of life and death. Lack of research and
      patent protection play a crucial role. Both are cost driven; greed in the West
      curtails the availability of life-saving drugs for all. Treatment options for
      trypanosomiasis and visceral leishmaniasis are lacking. It is recommended that
      drugs for the treatment of 'neglected diseases' be developed via a centralised,
      public approach that is not based on profit, rather than leaving it to free
      enterprise.

PMID- 10908953
TI  - [Mechanical ventilation in neuromuscular diseases: do not start too early, but
      certainly not too late].
AB  - Three patients had chronic respiratory disorders: a 42-year-old man with
      glycogenosis type II was tired, had headaches, poor pulmonary function values
      and, according to the arterial blood gas values, hypercapnia; a man aged 24 with
      Duchenne's muscular dystrophy had variable moderate dyspnoea with hypoxia and
      hypercapnia, and a man aged 64 years with an mitochondrial myopathy complained of
      dyspnoea and headache but had good blood gas values. The symptoms and
      abnormalities of the first patient were suppressed by nocturnal ventilatory
      support through a nasal mask system, the second preferred to refrain from
      ventilatory support and died a few weeks later and the symptoms of the third
      patient decreased without ventilatory support. Assessing a ventilatory disorder
      in patients with a neuromuscular disease is not always simple. Symptoms
      suggestive of nocturnal hypoventilation may occur in patients without respiratory
      insufficiency. It is also possible for patients with chronic respiratory
      insufficiency to be free of symptoms. Determinations of the arterial blood gas
      values are the most reliable method. Since normal daytime values do not exclude a
      nocturnal respiratory insufficiency, it is advisable in case of suspicion of
      nocturnal hypoventilation to measure the arterial blood gas values at night, as
      well. Nocturnal pulse oximetry does not always adequately reflect the degree of
      hypoventilation. In view of the positive effects of assisted respiration,
      adequate diagnostic examinations and early referral to a centre for home
      mechanical ventilation are advisable.

PMID- 10908955
TI  - [Evaluation of added value of diagnostic tests].
AB  - In the evaluation of diagnostic tests emphasis is placed on the evaluation of a
      particular diagnostic test in order to estimate it's sensitivity, specificity, or
      area under the 'receiver operating characteristic' curve (so called test
      research). This kind of test research is only useful in situations in which a
      diagnosis is set by one test (i.e. screening) and in the initial phases of test
      development for efficiency reasons. But, test research is not suitable to
      evaluate the clinical or added value of a test. The value of a diagnostic test
      can be evaluated on its value to discriminate between the presence and absence of
      a particular disease, to guide therapeutic decisions and to improve the prognosis
      of the patient. For evaluation of the added value of a diagnostic test within the
      diagnostic process, the study design should take into account the patient group
      in which the test will be applied in practice, the target disease of the test and
      the prior probability (prevalence) of the target disease in that population, the
      subsequent diagnostic stages and the reference test. In analysing the data it is
      calculated for each step of the diagnostic process how the test result changes
      the probability of presence or absence of the target disease.

PMID- 10908956
TI  - [Choice of ear drops in chronic otorrhea].
AB  - In chronic otitis, the use of ear drops has certain advantages over the use of
      systemic antibiotics. The choice of ear drop depends on the condition of the
      eardrum, microbial pathogens present and the efficacy of the components of the
      ear drop. Ototoxicity, contact allergy and the development of bacterial
      resistance have to be taken into account. Ototoxicity is a rare complication of
      the application of ear drops, most often described when aminoglycosides were
      applied. Contact allergy is also most often seen in aminoglycoside-containing
      eardrops. Evaluation of ear swabs demonstrated a 5% resistance of Pseudomonas
      aeruginosa to ciprofloxacin. The appearance of resistant strains may impede
      systemic use of fluoroquinolones. Therefore, this class of antibiotics should be
      considered as reserve medication only. The first choice in local application of
      antiseptics in case of an open eardrum is aluminium acetotartrate 1.2% and, of a
      combination preparation, bacitracin-colistin-hydrocortisone. In case of a closed
      eardrum (external otitis) aluminium acetotartrate 12%--combination preparations
      with corticosteroids are advised against in these cases.

PMID- 10908957
TI  - [Physical examination--tourniquet tests for varicose veins].
AB  - Physical examination of patients with varicose veins is time-consuming and
      subjective. Nowadays, it is frequently replaced by hand-held Doppler examination
      and duplex scanning. Adequate studies investigating the value of physical
      examination for varicose veins are lacking. It is unclear whether the tourniquet
      tests of Trendelenburg and Perthes are more accurate than other physical tests,
      such as the cough test or tap test. In selected patients, who are not obese, have
      clearly visible varicose veins and have not been treated before, physical
      examination seems accurate, especially for assessment of the long saphenous vein.
      When physical examination is inconclusive, as often is the case with recurrent
      varicose veins, suspected short saphenous vein or perforator incompetence, or
      adipose legs, additional Doppler or duplex testing is required for an accurate
      diagnosis.

PMID- 10908958
TI  - [Surgical treatment of distal esophageal perforation not due to a malignancy:
      results in 11 patients, University Medical Center Utrecht, 1994-1998].
AB  - OBJECTIVE: To describe the surgical treatment of distal oesophageal perforation
      and its results. DESIGN: Retrospective. METHODS: From patient records data were
      collected on 11 patients, 6 men and 5 women (median age: 54 years; range: 21-76)
      who underwent surgery for distal oesophageal perforation in Utrecht University
      Medical Centre. There were 7 iatrogenic perforations, 3 after vomiting and 1
      perforation was based on an oesophageal stricture. Four patients had a delay < 24
      h and 7 > 24 h (range: 6-27 days). Nine presented with sepsis, mediastinitis and
      empyema. Seven underwent primary repair: 5 in combination with a
      hemifundoplication, 2 with omentomplasty. In the group of other surgical
      treatment, 2 had drainage with extension and diversion, 1 had an oesophageal
      resection and gastric conduit and 1 had only surgical drainage. RESULTS: Primary
      repair resulted in 7/7 survival. The median period of hospital stay was 24 days
      (range: 10-62), and the median stay on the ICU was 14 days (range: 0-21). Four
      patients underwent reoperation. Four patients with primary repair presented no
      functional complaints, 1 had reflux complaints and 2 dysphagia. Two out of four
      within other surgery survived the perforation.

PMID- 10908959
TI  - [Intracranial aneurysms and autosomal dominant polycystic kidney disease].
AB  - Three women aged 55, 47 and 40 years with polycystic kidney disease had several
      relatives with cystic kidneys, some of whom had died or been crippled after
      (presumably) a subarachnoid haemorrhage. Two of these patients had a haemorrhage
      from an aneurysm of a cerebral artery; after clipping of the vessel they
      recovered without sequelae. The third patient had magnetic resonance (MR)
      angiography performed, which revealed no aneurysm. The prevalence of
      intracranial, saccular aneurysms in patients with autosomal dominant polycystic
      kidney disease (ADPKD) is about 10%. ADPKD patients with questions about the risk
      of a subarachnoid haemorrhage should be informed about the need of blood pressure
      control and the possibility of screening by MR angiography. Diagnosed aneurysms
      can be treated neurosurgically or endovascularly. Since aneurysms develop in the
      course of life, screening as a rule is only necessary from the age of 20 years,
      and its repetition every 5 years should be considered.

PMID- 10908960
TI  - [Role of the morning report in the training of internists].
AB  - The morning report constitutes an important part of the daily routine in the
      Department of Internal Medicine. According to the literature, this procedure
      makes an effective contribution to the training of internists, provided that a
      number of conditions are fulfilled (a critical but not hostile atmosphere, broad
      participation, a large number of patients). We compared the diseases discussed in
      the morning report retrospectively with the final attainment levels for the
      training of internists as described in the recently published 'Outline of
      Internal Medicine'. Of the diseases described in this outline, almost two-thirds
      (62.4%) had been discussed on the morning report within a period of 6 months. The
      morning report would seem to be an important addition to the other forms of
      knowledge transfer within the training of internists.

PMID- 10908961
TI  - Vestibular schwannoma growth--long-term results.
AB  - The growth of vestibular schwannoma (VS) was investigated in a series of 123
      patients with 127 tumours during 3 periods: 1973 to 1993 (mean observation period
      3.4 years), 1973 to 1996 (mean observation period 3.8 years) and 1973 to 1999
      (mean observation period 4.2 years). Three sets of growth results were obtained.
      At the end of the first period, 94 tumours (74%) exhibited measurable growth, 23
      tumours (18%) no measurable growth and 10 tumours (8%) negative growth. Tumour
      growth was observed in 104 tumours (82%), no tumour growth in 15 tumours (12%)
      and negative growth in 8 tumours (6%) at the end of the extended observation
      period. Growth was observed in 108 tumours (85%), no growth in 11 tumours (9%)
      and negative growth in 8 tumours (6%) subsequent to the third observation period.
      However, the results can be interpreted in another way: 52 patients (42%) are
      alive, tumour growth required no intervention; 23 patients (19%) died due to non
      tumour-related causes; and 35 patients (28%) were previously treated and alive by
      the end of the third observation period. Together with other factors, the results
      reported here should be considered when timing of surgery is to be decided.

PMID- 10908963
TI  - Cochleovestibular symptoms related to the site of vestibular schwannoma.
AB  - The purpose of the investigation was to study the symptoms that may provide clues
      to the early diagnosis of vestibular schwannoma (VS). The symptoms associated
      with VS in 41 patients were compared with the tumour locations detected by
      magnetic resonance imaging (MRI). There were 9 (22%) mainly intracanalicular and
      32 (78%) mainly extracanalicular tumours. MRI visualized the enhancement of the
      intracanalicular nerve in 27 of 32 extracanalicular schwannomas. Hearing
      impairment was found as an initial symptom equally frequently in patients with
      intra- or extracanalicular VS. Tinnitus was reported as the first symptom more
      often in patients with extracanalicular VS and dizziness more often in patients
      with intracanalicular tumours. At the time of diagnosis, unilateral hearing loss
      was present in 98% of patients, independent of tumour location. Likewise,
      dizziness was found equally frequently in both patient groups. Instead, tinnitus
      was found almost significantly more frequently in patients with intracanalicular
      VS (p = 0.07). Although statistically insignificantly so, neurological symptoms
      were more common in patients with extracanalicular VS (p = 0.45).

PMID- 10908962
TI  - Cystic vestibular schwannoma--clinical and experimental studies.
AB  - The cystic variant of vestibular schwannoma (VS) presents a therapeutic dilemma.
      Several studies have previously demonstrated that the surgical outcome in this
      tumour entity is less favourable than that of solid tumours of comparable size.
      The "wait and scan" policy has not been recommended for these tumours, as the
      cystic elements expand, causing displacement of the brainstem and compression of
      the 4th ventricle, resulting in hydrocephalus. The large tumour size at diagnosis
      and the cystic contents do not support the role of radiosurgery as a therapeutic
      option. We have previously published the surgical outcome of 23 cystic VS. The
      present study includes 44 patients (44 cystic tumours) in a series of 773 tumours
      (5.7%) who underwent surgery in the period 1976 to 1996. This paper presents the
      neuroradiological and histological features of the tumours, as well as the
      results of tumour specimen implantation and surgery in athymic nude mice.
      Therapeutic options are also discussed.

PMID- 10908964
TI  - Vestibular schwannoma mimicking Meniere's disease.
AB  - We retrieved information on 128 patients with vestibular schwannoma (VS) and 243
      patients with Meniere's disease (MD) from the database of the otoneurologic
      expert system (ONE). The patients filled in a questionnaire concerning their
      symptoms, earlier diseases, accidents and tobacco and alcohol use. This
      information was then integrated with results of audiometric, otoneurologic and
      imaging studies. Forty-nine (38%) of the VS patients had the full triad of
      vertigo, hearing loss and tinnitus. The vertigo mimicked that in MD in 18 (14%)
      patients. The mean age of these patients was 48 years. There were 7 men and 11
      women. The tumour was small (< 2 cm) in eight patients and medium-sized (2-4 cm)
      in seven patients. The mean attack duration in these 18 patients ranged from 5
      min to 4 h. The attacks most commonly (69%) occurred only once or twice a year.
      Their intensity was moderate. Half of the patients had spontaneous nystagmus.
      Caloric asymmetry > 25% was detected in 61% of the patients. Tinnitus in these
      patients was mostly (49%) mild. Intense tinnitus was present only in 12% of
      patients. Headache was present in 25% of these patients.

PMID- 10908965
TI  - Vertigo in patients with benign paroxysmal positional vertigo.
AB  - We retrieved information on 59 patients, 19 men and 40 women, with benign
      paroxysmal positional vertigo (BPPV) from the database of the otoneurologic
      expert system (ONE). The original number of patients was greater, but we excluded
      all those with hearing loss of any origin. The patients filled in a questionnaire
      concerning their symptoms, earlier diseases, accidents and tobacco and alcohol
      use. This information was then integrated with results of audiometric,
      otoneurologic and imaging studies. The mean age at onset of symptoms was 44
      years. Most patients had had vertiginous spells for < 1 year. None of the
      patients had hearing loss. Tinnitus was experienced by 32% of patients, and these
      patients experienced more anxiety than the others [r(53) = 0.40, p < 0.01]. The
      mean duration of the vertigo attacks ranged from a few seconds to 5 min, and they
      were fairly mild (26%) or moderate (41%) in intensity. The attacks were perceived
      as more intense if vertigo was rotational [r(54) = 0.60, p < 0.01] or if it was
      accompanied by nausea [r(58) = 0.42, p < 0.01]. Patients with headache had more
      intense attacks [r(58) = 0.36, p < 0.01]. The vertigo attacks occurred in spells;
      patients had several attacks a week (23%) or during the course of 1 day (52%).
      The vertigo was rotational in 80% of patients, and 47% experienced a floating
      sensation. The floating vertigo was most often provoked by pressure changes
      [r(54) = 0.41, p < 0.01] or changes in visual surroundings [r(54) = 0.52, p <
      0.01].

PMID- 10908967
TI  - Is hearing preservation worthwhile in vestibular schwannoma surgery?
AB  - The purpose of the study was to evaluate the usefulness of hearing preservation
      in vestibular schwannoma (VS) surgery. Hearing preservation was attempted in 123
      of 383 patients operated on during the years 1979 to 1993 at Helsinki University
      Hospital. Hearing was preserved in 47 cases. Pure-tone averages (PTA) better than
      30 dB were found in 12 cases postoperatively. Seventy percent of the patients
      rated their hearing preservation as valuable or very valuable. Only 8% did not
      find hearing preservation useful. Postoperatively, tinnitus was present in 62% of
      the patients, and it was a moderate problem in only 23% of the patients. In only
      one subject was the tinnitus a handicap that reduced the quality of life. Based
      on these experiences, we encourage surgeons to continue efforts to preserve
      hearing in VS surgery.

PMID- 10908966
TI  - Vestibular schwannoma surgery and headache.
AB  - The aim of the study was to evaluate aetiological factors for postoperative
      headache after vestibular schwannoma (VS) surgery with respect to asymmetric
      activation of vestibular reflexes. After surgery, 27 VS patients with persistent
      postoperative headache, 16 VS patients without headache and 9 healthy controls
      were examined. The vestibular, cervicocollic and cervicospinal reflexes were
      evaluated to study whether asymmetric activation of vestibular reflexes could
      cause headache. The effect of neck muscle and occipital nerve anaesthesia and the
      effect of sumatriptan on headache were also evaluated. The vestibular function of
      VS patients with headache did not differ from that of VS patients without
      headache, but was abnormal when compared to that of normal controls. The
      cervicospinal and cervicocollic reflexes did not differ in the patient groups.
      Injection of lidocaine around the operation scar gave pain relief to two
      patients, and one of them had occipital nerve entrapment. Infiltration of
      lidocaine deep in the neck muscles in the vicinity of the C2 root did not
      alleviate headache, but caused vertigo. Nine patients with musculogenic headache
      got pain relief from supportive neck collars, and two patients with
      cervicobrachial syndrome got pain relief from manual neck traction. The study
      shows that asymmetric activation of cervicocollic reflexes does not seem to be
      the reason for headache. Headache seems to be linked to neuropathic pain,
      allegedly caused by trigeminal irritation of the inner ear and the posterior
      fossa, which has recently been linked to vascular pain.

PMID- 10908968
TI  - Tinnitus and vestibular schwannoma surgery.
AB  - The aim of this study was to evaluate the effect of operation on tinnitus in
      vestibular schwannoma (VS) patients. Altogether, 251 VS patients who underwent
      surgery during the years 1979 to 1993 at Helsinki University Central Hospital
      were included in the study. Information on preoperative tinnitus was collected
      from previously acquired data and postoperative tinnitus was evaluated.
      Preoperatively, 62.6% of the patients had experienced tinnitus. Of those with
      preoperative tinnitus, 47.4% also had it postoperatively, but of those 93
      patients without preoperative tinnitus, 39.8% had tinnitus postoperatively.
      Tinnitus is one of the primary symptoms of VS, together with hearing impairment
      and disequilibrium. The risk of postoperative tinnitus is almost 40%, and with
      preoperative tinnitus, the risk is 7.6% higher. In the majority tinnitus was not
      related to the surgery. Only a few patients had severe problems with tinnitus;
      difficulty understanding speech was the major complaint.

PMID- 10908969
TI  - Incidence and growth pattern of vestibular schwannomas in a Danish county, 1977
      98.
AB  - During a period of 21 years 162 acoustic neuromas or vestibular schwannomas (VS)
      were diagnosed in the county of Aarhus. During this period the incidence
      increased gradually, probably due to improvement of the quality of computed
      tomography imaging (CTI), and more widely available access to magnetic resonance
      imaging (MRI). Sixty-four patients were followed up by repeated CTI or MRI,
      whereas the remaining patients were referred for immediate operation. Six of the
      observed patients had their tumours removed after demonstration of continuous
      tumour growth. The observation of 64 tumours over periods between 5 months and 15
      years provided useful information on the natural history of sporadic VS. Our
      results showed that 14 VS (22%) regressed, 35 VS (55%) did not grow or had only
      minimal growth (growth rate up to 1 mm/year), whereas 15 VS (23%) grew > 1
      mm/year. All VS with positive growth had regular growth patterns.

PMID- 10908970
TI  - Acoustic neuroma--treatment modalities. Surgery, gamma-knife or observation?
AB  - We present our results of 211 patients with acoustic neuroma over a period of 10
      years, 1988-97. We operated on 100 and 111 had Gamma-knife (GK) treatment (69
      were available to follow-up). The results are excellent for surgery on small and
      intracanalicular tumours. In tumours of the same size, surgery and GK treatment
      give comparable, but somewhat different, results. In the GK group of 54 primary
      treated patients, 3 patients had to be operated on and another 4 developed
      hydrocephalus. A group of 35 acoustic tumours was observed for more than 3 years.
      Nineteen did grow (54%). Hearing was unchanged in 23%. We performed surgery in 11
      patients and gave 2 patients GK treatment because of tumour growth of > 2 mm in
      diameter a year. We conclude that either treatment is effective for small and
      medium-sized acoustic neuromas. Hearing preservation was best in the GK-treated
      group (80%), compared to only 12.5% in the group operated via the suboccipital
      route. Larger tumours and most medium-sized tumours should be operated, as should
      smaller tumours with persistent symptoms of vertigo and pain. Medical
      contraindications to surgery or reluctance to undergo surgery make GK treatment a
      good alternative. Treatment of residual tumours with the GK could also be a
      solution to a difficult problem.

PMID- 10908971
TI  - Intracanalicular vestibular schwannoma--therapeutic options.
AB  - The growth of purely intrameatal vestibular schwannoma (VS) was investigated in a
      series of 40 patients with 40 unilateral VS in the period 1973 to 1996 (mean 3.6
      years). Twenty-seven tumours (67.5%) revealed growth and 13 tumours (32%) had no
      measurable growth. Four growth patterns were observed: (i) 15 tumours (37.5%)
      exhibited constant growth; (ii) 13 tumours (32.5%) had no measurable growth;
      (iii) 8 tumours (20%) revealed growth subsequent to a no-growth period; and (iv)
      4 tumours (10%) manifested different growth patterns during the observation
      period. The mean diameter growth per year was 3.2 mm. The findings of the present
      study, especially those achieved in groups B (the non-growing tumours) and C
      (tumour growth subsequent to a silent period), question the reliability of the
      results achieved by radiosurgery, as no tumour growth may occur with no
      intervention.

PMID- 10908972
TI  - Electronystagmographic findings in patients with acute cerebral vascular disease
      and vertigo.
AB  - A neurootologist examined 233 successive cases of acute disabling vertigo from
      the Clinic of Neurology of Turku University Central Hospital. On magnetic
      resonance imaging (MRI), 24 patients had evidence of acute cerebral or cerebellar
      brain infarction. The examination scheme included a case history analysis,
      clinical neurootological examination and electronystagmography (ENG). The
      audiological examination included pure-tone thresholds and speech audiometry. The
      ENG analyses were done by two neurootologists who had no information about the
      aetiology of the diseases. A central disturbance in ENG was observed in 59%
      (10/17) of the patients with cerebral brain infarction and 71% (5/7) of the
      patients with cerebellar brain infarction. ENG is not valid as a screening method
      for the central aetiology of vertigo; imaging of the central nervous system is
      needed.

PMID- 10908973
TI  - Postural-induced changes in intracranial pressure evaluated non-invasively using
      the MMS-10 tympanic displacement analyser in healthy volunteers.
AB  - Inner ear pressure reflects intracranial pressure (ICP) primarily because of the
      direct communication of perilymph and cerebrospinal fluid (CSF) through the
      cochlear aqueduct (CA). The MMS-10 tympanic displacement analyser (TDA) is a
      relatively new device for measuring perilymphatic pressure non-invasively, and
      thereby also indirectly measuring intracranial pressure. The aim of the present
      study was to evaluate the use of the TDA in a daily clinical setting. Other aims
      were to investigate changes in perilymphatic pressure from sitting to lying
      position in healthy volunteers in two age groups (mean age: 33 years and 50
      years) and to compare the patency of the CA in these groups using the MMS-10 TDA.
      Tympanic membrane displacement (TMD) analyses were performed in the test subjects
      initially twice in sitting position (test-retest) and then in sitting and supine
      positions. We found that the MMS-10 TDA is easy to use, and that it gives
      reproducible values in repeated tests, but with large inter-subject differences.
      The TMD test showed curves, which, in the whole test group, were more negative in
      supine position, in accordance with an increasing intracranial and inner ear
      pressure when lying down. The change from sitting to lying position was larger in
      the younger group than in the older group. In 11% of the younger group (males)
      and in 30% of the older group (females), the CA was considered to be non-patent,
      although the difference was not statistically significant. However, the finding
      is in keeping with the hypothesis of a greater proportion of patent CA in younger
      than in older individuals.

PMID- 10908974
TI  - Otitis media as a sign of Wegener's granulomatosis in childhood.
AB  - Wegener's granulomatosis (WG) is a rare disease among paediatric patients.
      Chronic otitis media with or without facial nerve dysfunction is a known
      manifestation of the disease among adults. A case of a 15-year-old boy with WG,
      whose initial symptoms were acute otitis media and facial nerve paralysis, is
      presented. The otorhinolaryngological manifestations, as well as diagnostic and
      current treatment modalities in paediatric patients with WG, are discussed.

PMID- 10908975
TI  - Prevalence of chronic otitis media in a randomly selected population from two
      communes in southern Vietnam.
AB  - The prevalence of chronic otitis media was studied in an urban and a rural
      community in southern Vietnam in 1995. A total of 3,300 children, aged from 6
      months to 10 years, were selected randomly by taking every third child on the
      vaccination list. In this cross-sectional study, 453 ears were found to have
      chronic otitis media or sequelae otitidis, giving an overall prevalence of 6.86%.
      A total of 140 ears had perforations. Various attic changes were found in 73 ears
      and other chronic tympanic membrane changes, such as atrophy, tympanosclerosis
      and adhesions, in 219 ears. Cholesteatoma was seen in two ears.

PMID- 10908976
TI  - Middle ear secretory capacity after acute otitis media caused by Streptococcus
      pneumoniae, Moraxella catarrhalis, non-typeable or type B Haemophilus influenzae.
      A comparative analysis based on goblet cell density.
AB  - To investigate whether the type of bacteria is correlated with an increase in
      goblet cell density during and after acute otitis media, we inoculated the middle
      ear of 25 rats with either Streptococcus pneumoniae, Moraxella catarrhalis, non
      typeable or type b Haemophilus influenzae. Mucosal goblet cell density was
      determined by a whole-mount method on days 4, 8, 16, 60 and 180 post-inoculation.
      The goblet cell density was increased on all days of sacrifice, employing either
      bacteria, except M. catarrhalis 6 months after the acute incident. Type b H.
      influenzae induced the highest increase, followed by non-typeable H. influenzae,
      S. pneumoniae and M. catarrhalis. The mucosal area containing goblet cells was
      enlarged on all examination days, employing either bacteria. We conclude, that
      mucosal secretory capacity is highly increased during and up to 6 months after
      acute middle ear infection caused by either bacteria, conceivably predisposing a
      subsequent development of secretory otitis media. The results indicate that type
      b H. influenzae seems to be the bacteria most likely to induce a subsequent
      secretory condition.

PMID- 10908977
TI  - Effect of penicillin on experimental acute otitis media. A histopathological
      study of goblet cell density, bone modelling dynamics, polyp and adhesion
      formation.
AB  - Clinical studies have shown that the effect of antibiotic treatment on acute
      otitis media is modest. Experimental acute otitis media induces a number of
      histopathological changes in the middle ear mucosa. Among these are increased
      goblet cell density, polyp and adhesion formation, as well as massive
      osteoneogenesis. To investigate the effect of penicillin administration on these
      histopathological features, we employed a rat model of acute pneumococcal otitis
      media. Five of 25 rats were sacrificed on days 4, 8, 16, 90 and 180 post
      inoculation, preceded by oral administration of penicillin V 100 mg/kg/day,
      initiated on day 2 and lasting 5 days. Using a light microscope, qualitative and
      quantitative histopathology of middle ear goblet cell density, bone-modelling
      dynamics, polyp and adhesion formation was registered and compared with previous
      studies of untreated animals. Increase in goblet cell density and new bone
      formation was reduced significantly by treatment, whereas polyp and adhesion
      formation was unaffected by penicillin administration. It is concluded that
      penicillin reduces middle ear secretory capacity and new bone formation during
      and following acute otitis media, conceivably preventing subsequent development
      of secretory otitis media, leaving polyp and adhesion formation unchanged.

PMID- 10908979
TI  - Palatal myoclonus and clicking tinnitus in a 12-year-old girl--case report.
AB  - Palatal myoclonus is a rare neurological disorder of the soft palate and other
      oropharyngeal muscles, which causes clicking tinnitus. The latter is audible both
      to the patient and to an observer. The aetiology may be a brain stem lesion, and
      it is only rarely that a cause cannot be identified. The condition has been
      described in adults, but seldom in children. We present here a case of palatal
      myoclonus with distressing tinnitus in a 12-year-old girl and its successful
      treatment with electromyography (EMG)-guided injections of Clostridium botulinum
      toxin.

PMID- 10908978
TI  - Tympanometric hysteresis effect and errors in middle ear pressure determination-
      a preliminary study in children with secretory otitis media.
AB  - Previous tympanometric studies on middle ear pressure (MEP) have revealed the
      hysteresis effect, which is illustrated in bidirectional tympanometries by the
      different peak pressures for either direction. This leads to an error in
      determination of MEP, which has been reported to be 10-25 daPa in normal ears,
      but experimental data have suggested that this error may be increased in ears
      with secretory otitis media (SOM). This was investigated in a group of 18
      children with SOM by bidirectional tympanometries. The peak pressure difference
      (PPD) was calculated and found to be 75 daPa in the group of SOM, which was
      significantly larger than in normal ears (mean = 3 daPa) (p < 0.001). The maximum
      PPD in the SOM group was 205 daPa, indicating an error in MEP determination of
      more than 100 daPa. Hysteresis is related to the viscous properties of the middle
      ear system, and the increased hysteresis in SOM ears can be explained by the
      additional viscosity of the middle ear effusion. In order to improve the accuracy
      of MEP estimation it is suggested that in ears with SOM, the mean pressure of
      bidirectional tympanometries should be applied.

PMID- 10908980
TI  - Clinical outcome of acute pneumococcal otitis media and serum antibody responses
      to pneumococcal pneumolysin and polysaccharides in children.
AB  - Serum antibody responses to pneumococcal antigens and their relationship to the
      clinical outcome were determined in a prospective study of 121 children with
      acute otitis media (AOM). Pneumococcus positive children with a pneumolysin
      response more often had a recurrence and middle ear effusion (MEE) after 1 month
      than did the non-responders (p = 0.005 and p = 0.04, respectively). All the
      children who responded to pneumolysin also had clinically strong symptoms and
      signs of AOM. Children who responded to pneumococcal polysaccharides developed
      otitis media with effusion within a 6-month follow-up period more often than did
      the non-responders (p = 0.005). The results of this study suggest that children
      with pneumococcal AOM and an antibody response to the intracellular pneumococcal
      protein pneumolysin behave clinically differently from children with an antibody
      response to polysaccharides.

PMID- 10908981
TI  - Factors associated with the development of recurrent acute otitis media--the
      significance of choosing the right and accurate dependent and independent
      variables in the multivariate analysis.
AB  - The results of univariate and multivariate statistical analysis were compared in
      identifying predictive factors of the development of recurrent acuta otitis media
      (RAOM) after an initial episode of acute otitis media (AOM) in 121 children.
      Univariate correlations between the development of RAOM and potential risk
      factors were analysed, and variables at p < 0.10 were incorporated into the
      stepwise multiple logistic regression analysis. The comparisons between the
      univariate and multivariate analysis in identifying the predictive factors were
      made and the importance of changing the dependent variables in the multivariate
      analysis was analysed. It seems that univariate analysis is over-sensitive, but
      multivariate analysis is over-conservative in finding possible predictors of
      RAOM. Choosing the right and accurate dependent and independent variables in the
      multivariate analysis is extremely important, when this method is used.

PMID- 10908983
TI  - Lasting effects of otitis media with effusion on language skills and listening
      performance.
AB  - Otitis media with effusion (OME) and its related hearing loss has been associated
      with delayed language development, particularly if the disease is recurrent or of
      long duration. To find out more about the long-term effects of OME on language
      skills and listening performance we performed a retrospective study. A group of
      19 otherwise healthy 9-year-old children with an earlier history of long lasting
      bilateral OME were compared with an age-matched control group of 19 children with
      no history of OME or hearing impairment and normal otoscopy, tympanometry and
      audiometry. The children in the OME group had an average of 1.4 treatments with
      ventilation tubes. Mean hearing levels for 500, 1,000 and 2,000 Hz in the OME
      group were 13 dB in the right ear and 11.3 dB in the left ear. All children were
      examined with the Illinois test of psycholinguistic abilities (ITPA), test for
      articulation, Boston naming test, dichotic listening tests with additional tasks
      of directed attention and tests for word and sound discrimination. In the OME
      group we found significant lower scores in the articulation test and small, but
      significant, lower scores in the test regarding sound discrimination. No
      significant differences on other language skills were detected in the ITPA test
      or Boston naming test. We found a significantly higher degree of right ear
      advantage and lower attentional effectiveness in the OME-group.

PMID- 10908982
TI  - Hereditary hearing loss--the role of environmental factors.
AB  - A large family with mid onset sensorineural hearing loss (HL) was used to study
      the effect of environmental factors on progression HL. Data from five-generations
      of one family were traced and 104 living members were included in the study.
      Audiograms were measured for 60 family members. We used an expert program to
      study the individual risk factors, which included the known risk factors for
      sensorineural HL. The pattern of inheritance in this HL family was autosomal
      dominant and 22 individuals were affected. The HL among affected individuals was
      symmetrical and varied from mild to severe. The mean age at onset of HL was 22
      years. The mean deterioration of hearing at 2 kHz frequency was 1 dB/year. In the
      risk analysis the use of NSAID-analgetics and military noise exposure correlated
      with HL. There was no correlation between occupational and free time noise
      exposure and HL. Analgetics may aggravate the HL in subjects with inherited HL.
      This type of genetic lesion is new and is not in those chromosomal areas already
      documented in the literature.

PMID- 10908984
TI  - Treatment of severe tinnitus.
AB  - In 1995-96 we selected a group of 26 patients who were suffering from severe
      invalidating idiopathic tinnitus (IT) in order to evaluate the efficacy of
      rehabilitation and some alternative therapies. All patients were assessed
      thoroughly by means of audiology and radiology regarding any objective cause for
      the symptom. In order to help patients control their symptom by increasing
      knowledge and adding supportive elements, they were given basic education
      (presentations of the anatomy and physiology of the ear and hearing system,
      psychological and social aspects of IT, guided and non-guided group discussions,
      relaxation therapy, physiotherapy, music therapy) for 4 months, comprising one 2
      h session bi-weekly. This type of group therapy was found to be extremely
      helpful, although no objective evaluation revealed effects on IT sensation (VAS)
      or psychometric measures (SLC-90). In a second limb of the study, the same
      patients attended a 6-day intensive course in a spa. The purpose was to evaluate
      the possible usefulness of the widely recommended alternative therapies for IT.
      All patients had an opportunity to sample the treatments. Six months later only a
      few had tried any of these treatments, but all reported that the lessons were the
      most helpful in association with supportive group discussions. The results
      indicated that none of these therapies can be recommended, based on rational
      medical practise.

PMID- 10908985
TI  - Effect of N-acetylcysteine on the incidence of recurrence of otitis media with
      effusion and re-insertion of ventilation tubes.
AB  - Previous studies have demonstrated the anti-inflammatory, anti-oxidant, and
      mucolytic nature of N-acetylcysteine (NAC). Theoretically, these properties make
      the substance ideal for therapeutic use against otitis media with effusion (OME).
      The disease is characterized as a sustained non-specific inflammation of the
      middle ear mucosa with secretory transformation of the epithelium resulting in
      accumulation of fluid in the middle ear space. To investigate the effects of
      instillation of NAC in the middle ear, a double-blind, placebo-controlled,
      randomized trial was carried out. A total of 75 children who were undergoing
      their first bilateral insertion of ventilation tubes (VT) due to OME were
      randomized to Mucomyst (NAC) or placebo (the vehicle) on one ear in relation to
      the VT insertion. The contralateral ear underwent VT insertion exclusively.
      Instillation of Mucomyst or placebo was repeated 3 and 7 days afterwards. The
      children were followed regularly for 11-39 months. Episodes of otorrhea,
      recurrence of OME after VT extrusion and re-insertion of VTs were registered as
      primary outcome parameters. The results demonstrated that Mucomyst significantly
      reduced the recurrence of OME and re-insertion of VTs (p < 0.025) and
      significantly increased the time until VT extrusion (p < 0.0167). In addition,
      the number of episodes of ear problems and visits at the ENT clinic were reduced
      significantly by NAC (p < 0.0383).

PMID- 10908986
TI  - Auditory ossicles in archaeological skeletal material from medieval Denmark.
AB  - Auditory ossicles were collected from two skeletal materials from early medieval
      Denmark. A total of 147 and 1,162 ossicles were obtained from the 2 materials,
      constituting 23% and 55% of the possible in vivo ossicles. The numbers and
      percentages found are among the highest reported from studies of archaeological
      skeletal material. Archaeological ossicles may be used in palaeopathological
      evaluation of chronic otitis media and otosclerosis, and morphometric studies of
      the ossicles might be valuable in analysis of population genetics and taxonomy.

PMID- 10908987
TI  - Concentrations of the Pseudomonas aeruginosa toxin pyocyanin in human ear
      secretions.
AB  - Pseudomonas aeruginosa is the most common bacterium in chronic otitis media.
      Several extracellular factors have been described. Pyocyanin (Pyo) is the blue
      pigment that gives the bacterium its name "the pyocyanous bacteria". Pyo is known
      to have an inhibitory effect on the activity of cilia. It is a zwitterion that
      might easily penetrate biological membranes. Samples of ear secretions for
      culture and analysis of the concentration of Pyo were collected from 17 patients
      with different ear infections. Concentrations varied from 3 to 2714 nmol/g, with
      a mean of 905 nmol/g. For comparison, concentrations were also measured in
      bacteriological filtrates of P. aeruginosa obtained from wounds and urine
      specimens. Concentrations in filtrates varied from 13 to 8114 nmol/g, mean 1968
      nmol/g. The results indicate that pyocyanin might act as virulence factor that
      compromises ciliary function and enables the microorganism to establish itself
      within the ear.

PMID- 10908988
TI  - Middle ear epithelium has inflammatory capacity.
AB  - Endotoxin, tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1
      beta) and intercellular adhesion molecule-1 (ICAM-1) were detected in 88%, 51%,
      58% and 66% of 152 middle ears from patients suffering from otitis media with
      effusion. In this study the hypothesis that bacterial endotoxin, TNF-alpha, IL-1
      beta and ICAM-1 induce the inflammatory process characteristic of otitis media
      with effusion was tested. Cultures of rabbit middle ear epithelium were exposed
      to endotoxin, TNF-alpha or IL-1 beta. The expression of ICAM-1 on the cell
      surfaces was measured with a direct enzyme-linked immunosorbent assay on the cell
      layer. For TNF-alpha, 5 ng/ml significantly increased ICAM-1 expression, whereas
      100 ng/ml had a toxic effect. For IL-1 beta, as little as 1 ng/ml produced a
      significant increase in ICAM-1 expression. Endotoxin stimulated ICAM-1 expression
      less strongly in concentrations from 100 ng/ml to 100 micrograms/ml. The findings
      indicate that stimulation of ICAM-1 by endotoxin is mediated, at least in part,
      by TNF-alpha and IL-1 beta. It is concluded that endotoxin induces sustained
      inflammation in OME, and that this inflammation is mediated, at least in part, by
      the primary cytokines TNF-alpha and IL-1 beta.

PMID- 10908989
TI  - Cochlear implantation of Danish prelingually deaf children.
AB  - The aim of the study was to review the indications, techniques and results of
      cochlear implant (CI) treatment with the Nucleus CI multi-channel electrode for
      the first children operated on in Denmark. The study material comprised 16
      children (5 girls, 11 boys). Their median age at the time of CI operation was 27
      months. Anacusis was caused by pneumococcal meningitis in 31% of the children in
      this relatively young prelingual material. Obliteration of the cochlea was found
      in two children, indicating the need for surgery as soon as possible after the
      verification of post-meningitis, total deafness. There were no technical
      difficulties with operating on the youngest children in the congenital group and
      the age of 2 years is optimal for implantation. These preliminary results have
      contributed definitively to an increase in the number of cochlear implantations
      being carried out in young prelingually deaf Danish children.

PMID- 10908990
TI  - Effects of cerebrospinal fluid loss on hearing.
AB  - There is a direct communication between the cerebrospinal fluid (CSF) and the
      perilymph through the cochlear aqueduct (CA). Perilymph depletion due to
      perilymphatic fistulas has been demonstrated to influence inner ear function,
      with signs and symptoms similar in many ways to those of Meniere's disease. A
      leakage of CSF could also theoretically affect the inner ear. The present study
      was conducted to investigate whether hearing was affected in patients submitted
      to a leakage of CSF and, if so, to what extent, in which frequency range, which
      time course and incidence. The study comprised 126 patients who were exposed to
      different surgical procedures that involved puncture or incision of the dura, and
      a control group of 32 patients without such leakage. Hearing was reversibly
      affected only in patients with leak of CSF. The size of the hearing loss, the
      number of affected patients and the number of frequencies involved increased with
      increasing amount of CSF lost. Changes in the constituent cochlear fluids due to
      a transitory reduction in the CSF and the perilymphatic volume with a
      compensatory endolymphatic expansion may be responsible for the observed
      findings.

PMID- 10908991
TI  - Effects of middle ear pressure changes on clinical symptoms in patients with
      Meniere's disease--a clinical multicentre placebo-controlled study.
AB  - Different medical and surgical methods have been tried in attempting to reduce
      endolymphatic pressure in Meniere's disease. Pressure treatment has a role on the
      treatment staircase, after pharmacological treatment and before destructive
      methods. Pressure chamber treatment has shown that some patients respond well to
      the treatment with diminishing inner ear symptoms and also some hearing
      improvement. Earlier studies have shown that electrocochlear measurements improve
      after local pressure treatment in the ear. The present study was a prospective
      randomized placebo controlled, multicentre clinical trial. 56 patients with
      active Meniere's disease, age 20-65 years, with a hearing loss of 20-65 dB PTA
      participated. A total of 31 patients completed 2 weeks use with an active
      apparatus (Meniett) and 25 patients completed the 2 weeks with the placebo
      gadget. Both machines were produced by Pascal Medical, Halmstad, Sweden. Two
      weeks before the start of treatment a grommet was placed in the tympanic
      membrane. A significant improvement concerning frequency and intensity of
      vertigo, dizziness, aural pressure and tinnitus was reported by the active group
      on the visual analogue scales (VAS) questionnaire. In the placebo group no change
      was the most common finding, followed by worsening of the symptoms and a few
      improvements. The function in professional and family life improved during active
      treatment and did not during placebo treatment. Pure-tone audiometry did not
      improve after placebo treatment, but improved at the frequencies 500 Hz and 1,000
      Hz after active treatment. The study showed an improvement in the inner ear
      symptoms after Meniett treatment. The mechanism may be explained by the influence
      on the round window membrane pressure receptors or an endolymphatic flow out
      through the pressure release points, such as the endolymphatic duct and sac, thus
      activating the longitudinal flow. Other mechanisms are also possible.

PMID- 10908992
TI  - Puromycin-induced lipid peroxidation in the cochlea of ApoE knockout mice.
AB  - Puromycin-treated apolipoprotein E (ApoE)-deficient mice were used to study lipid
      peroxidation (LPO) in the cochlea. Puromycin causes accelerated peroxidation of
      lipids and induces both inner ear and renal lesions in experimental animals
      presenting with abnormally high serum cholesterol. To prevent LPO, we used
      probucol, an effective inhibitor of LPO, and, simultaneously, also a lipid
      lowering drug. The mice were given a single injection of the aminonucleoside of
      puromycin (25 mg/100 g). Polyclonal malondialdehyde and 4-hydroxynonenal
      antibodies were used to localize the LPO products. LPO products were mainly found
      in the stria vascularis of puromycin-treated mice. No LPO products were observed
      in the hair cells. LPO product immunoreactivity was clearly diminished in the
      animal group treated with both puromycin and probucol. In the cochlea of the ApoE
      deficient mouse, puromycin affects mainly the stria vascularis due to the
      accelerated peroxidation of structural lipids. Probucol treatment prevented the
      formation of LPO products.

PMID- 10908993
TI  - Titanium implants for bone-anchored hearing aids--host reaction.
AB  - In a series of 31 prospectively followed patients equipped with bone-anchored
      hearing aids (BAHA), 7 titanium implants (19.4%) were lost in 6 patients after a
      median of 42 months (range: 27-78 months), often after visible resorption of bone
      around the superficial part of the implant. Expressed in a sample life table, no
      implants were lost during the first 2 years. After 3-4 years, the success rate
      dropped to about 85% and after 6-7 years to about 75%. Research that aims to
      define the factors which influence the extrusion rate is needed.

PMID- 10908994
TI  - Round window gentamicin mu-catheter--a new therapeutic tool in Meniere's disease.
AB  - The vestibulotoxic effect of gentamicin is well documented; however, there is no
      general agreement on the gentamicin dose needed to control vertigo attacks
      without affecting the hearing. In the current study, 14 patients with Meniere's
      disease refractory to medical treatment were treated by small doses of gentamicin
      delivered via a mu-catheter, placed into the round window niche. An electronic
      micropump delivered 10 microliters (100 micrograms)/h. The patients received a
      total dose of 4-14 mg. The effects on the vestibular symptoms were most
      encouraging, with cessation of vertigo in 13 of the 14 patients, control of
      Tumarkin attacks in 4 out of 6 cases and release of aural pressure and fullness
      in 2 out of 4 cases. According to the recommendations of the Committee on Hearing
      and Equilibrium, the patients in this material belonged to functional levels 5
      and 6. At the last clinical follow-up, five patients were classified as level 1,
      eight patients as level 2 and one patient as level 3. A significant hearing loss
      was seen in one patient; however, this was most likely due to the natural
      development of the disease in this particular case. The results look promising,
      but must be investigated further in a placebo-controlled study.

PMID- 10908995
TI  - Predilection of otosclerotic foci related to the bone turnover in the otic
      capsule.
AB  - Using multiple fluorochrome tagging of eight mongrel dogs and a newly established
      methodology of measuring bone turnover (BTO) in the otic capsule, it has
      previously been demonstrated that BTO in the canine otic capsule is highly
      reduced close to the perilymphatic spaces (PLS) compared to the normal level of
      BTO in the periphery. Reanalysis of these data shows that this inhibition of BTO
      is far more pronounced around the cochlea and vestibule than around the
      semicircular canals. Similar tendencies are seen for the numerical density and
      mean label area of the bone remodelling units. With increasing distance to the
      PLS, these patterns are weakened, but still recognizable. In otosclerosis, foci
      of abnormal bone deposition are particularly frequent around the oval and round
      windows and in the cochlear capsule, i.e. where inhibition of bone remodelling is
      most prominent. A surpassing (or failure) of this pronounced inhibition must
      precede the tumultuous but delimited osteogenesis of otosclerosis. Otosclerosis
      may be a deviation of the normal BTO process in an osteometabolically abnormal
      site, perhaps initiated as an osteogenetic response to abnormal stress exposure.

PMID- 10908996
TI  - Measurement of bone metal contact (BMC) in retrieved maxillofacial
      osseointegrated implants.
AB  - Eighteen screw-shaped extraoral osseointegrated implants retrieved from 10
      patients were analysed by microradiography. Retrieved implants were trephined
      with a border of surrounding bone, fixed, embedded in epon plastic, ground and
      processed for microradiography. The reasons for retrieval were unexplained pain
      (n = 4), inability to cope with the implants (n = 2), fracture of central screw
      (n = 2), skin penetration problems (n = 1) and trauma (n = 1). The study group
      comprised six males and four females with a mean age of 53.4 years (range: 9-81
      years). All implants were clinically stable at the time of removal, and mean
      osseointegration time was 3 years (range: 1-5 years). Six implants were removed
      from the temporal bone, five from the frontal bone and seven from the maxilla.
      Bone metal contact was estimated to vary between 27% and 83%. Bone metal contact
      was lower in the frontal bone compared to the temporal bone or maxilla, and was
      further reduced after preoperative irradiation. Longer osseointegration time
      increased bone metal contact, as did increased age up to 60 years. It is
      concluded that extraoral osseointegrated implants in humans may integrate
      morphologically as well as clinically. By microradiography it was possible to
      define bone metal contact in the region of implant installation.

PMID- 10908997
TI  - Osseointegrated implants in children.
AB  - This study was undertaken on 86 children aged 15 years or lower scheduled for
      installation of osseointegrated implants. Of these, 64 had implants installed for
      bone-anchored hearing aids (BAHA) or episthesis. The main indication for implant
      installation was a bilateral ear malformation. Surgery was generally performed as
      a two-stage procedure with a healing time of 3-4 months in between. Available
      bone thickness averaged 2.5 mm, and lack of bone necessitated bone augmentation
      in 12 patients. Forty-five percent of the implants were installed in contact with
      the dura, sigmoid sinus or an air cell. Of 129 installed fixtures, 6.2% were
      implant failures. Adverse skin reactions appeared in 7.6% of patients over a 17
      year follow-up period. Revision surgery was undertaken in 30% of patients due to
      appositional growth of the temporal bone. It is concluded that implant failures
      and skin reactions in this population are comparable to those in an adult group
      of implant patients, whereas revision surgery is more common in children.
      Nevertheless, osseointegrated implants can be used with good functional and
      aesthetic outcome in children.

PMID- 10908998
TI  - Acute mastoidectomy in a Danish county from 1977 to 1997--operative findings and
      long-term results.
AB  - Data from patients undergoing acute mastoidectomy were examined retrospectively
      to evaluate if the nature of acute mastoiditis (AM) treated surgically has
      changed during the last 20 years (1977-97). Moreover, a prevalence study was
      conducted to clarify the otological and audiological course following acute
      mastoidectomy. Patients with cholesteatoma and intracranial complications were
      excluded. Thus, 79 patients with a median age of 16 months were included. Thirty
      seven percent had a history of middle ear disease, and the mean duration from
      onset of symptoms to admission was 9 days. Well-being was affected in 46%, and
      82% had fever. The clinical picture was dominated by auricular protrusion (77%)
      and pathological tympanic membrane (94%). Postauricular oedema, hyperaemia and
      tenderness were demonstrated in 89%, 78% and 49% of cases, respectively.
      Peroperatively, purulent middle ear effusion was recognized in 92%, subperiosteal
      abscess in 66% and pus in the mastoid in 90%. Specimens revealed growth of
      pathogens in 58%, predominantly Gram-positive bacteria. The observation period
      was 1-20 years. The findings in operated ears were not significantly different
      from the contralateral non-operated ears concerning incidence of otitis media,
      hearing and ear canal volume. Conclusively, acute mastoidectomy is a safe and
      effective treatment to eliminate infection. The operation can be done with
      negligible risk and does not leave long-term sequelae.

PMID- 10908999
TI  - Transtympanic versus tympanic membrane electrocochleography in examining
      cochleovestibular disorders.
AB  - The use of electrocochleography (EcoG) is considered to be of clinical value in
      otological diagnosis. Non-invasive ear canal (EC) and tympanic membrane (TM) EcoG
      recording techniques, and invasive transtympanic (TT) technique are the methods
      used for objective assessment of cochlear function. In this study, eight adults
      (16 ears) with suspected Meniere's disease were examined using a newly designed,
      disposable tympanic electrode and a traditional, thin transtympanic needle. The
      amplitudes of the TT electrode responses were 4-6-fold larger than those produced
      by the TM electrode. The morphology of the waveforms for the two recording
      techniques was nearly identical. The mean amplitudes of the action potential (AP)
      obtained with the TM electrode were 2.39-3.73 microV, and with the TT electrode
      14.08-19.60 microV, depending on the stimulus intensity. For the summating
      potential (SP), the TM and TT electrodes had mean amplitudes of 0.82-1.60 microV
      and 3.53-5.81 microV respectively. The SP/AP ratios were larger with the TM
      electrode than with the TT electrode. They were inconsistent in four ears (25%)
      when measured with the TM and TT electrodes. All patients were more satisfied
      with the TT examination, since it was quite painless, unlike the TM examination.
      The authors recommend the use of the TT recording technique as a painless
      examination in which the electrode is close to the inner ear, allowing a good
      signal-to-noise ratio and large amplitudes. Diagnostic interpretations are easier
      and more reliable with the TT electrode than with the TM electrode.

PMID- 10909000
TI  - Tympanoplasty with ionomeric cement.
AB  - Patients with isolated erosion of the long incus process suffer from severe
      hearing loss caused by lack of continuity of the ossicular chain. This study is a
      retrospective evaluation of the hearing results using two different surgical
      procedures. Since January 1993, 12 consecutive patients with isolated erosion of
      the long incus process have been treated with a new surgical technique in which
      the ossicular chain was rebuilt with ionomeric cement. The results in hearing
      performance (mean pure-tone average (PTA) 0.5, 1 and 2 kHz) were evaluated pre-
      and post-surgery, and compared to those in a group of 20 historical controls who
      underwent surgery in 1991 and 1992 using incus autograft interposition. Among the
      12 index patients, 7 (58%) achieved improvement in PTA of > 10 dB, in 3 there was
      no difference and in 2 a slight decline. Among the 20 controls, 14 (70%) achieved
      improvement in PTA of > 10 dB, in 4 there was a slight improvement and in 2 a
      decline. The difference was not statistically significant. Hearing improvement
      using ionomeric cement in type II tympanoplasty was satisfactory. Reconstruction
      of the ossicular chain with ionomeric cement is recommended, as the procedure is
      easy to perform, presents less risk of damage to the stapes and cochlea, requires
      less extensive surgery and does not exclude other surgical methods in cases of
      reoperation.

PMID- 10909001
TI  - Efficiency of hyperbaric oxygen therapy in experimental acute acoustic trauma
      from firearms.
AB  - In acute acoustic trauma (AAT), excessive noise exposure causes rupture of cell
      membranes and decreased cochlear blood flow. This leads to decreased oxygen
      tension in inner ear fluids and reduction of a variety of different oxygen
      dependent cellular activities. Hyperbaric oxygen treatment (HBO) may help the
      cells suffering from hypoxia to survive. We exposed male Wistar rats to 60
      impulses of 162-dB SPL from a 7.62-mm assault rifle equipped with a blank
      adaptor. After the exposure, 15 animals were given HBO treatment for 90 min daily
      for 10 consecutive days at 0.25 MPa. After a survival time of 4 weeks, auditory
      brainstem responses were measured and the left cochleae processed for light
      microscopy. The impulse noise caused permanent damage to the cochlea of all
      animals, with the most severe lesions in the lower middle coil, where a
      significantly smaller number of hair cells was missing in the HBO-treated group.
      The morphological damage was also reflected in function, as measured by auditory
      brainstem responses, which showed the greatest threshold shifts at 6.0, 8.0 and
      10.0 kHz.

PMID- 10909002
TI  - Laser-assisted myringoplasty--technical aspects.
AB  - At lower power, lasers fuse collagen fibres and weld tissues. Welded collagen
      fibres make a solid bond and allow tissue growth along the bonded edges. Our aim
      was to study applicability of lasers in myringoplasty. We used a KTP-532 laser in
      outpatient myringoplasty. The laser beam was delivered through a micromanipulator
      connected to a microscope or through a 200-400-micron silica fibre. The
      perichondrium was used for transplantant and harvested from the tragus. The
      margins of the perforation in the eardrum were evaporated, with the laser
      operating in a continuous mode at 2-4 W. The middle ear was filled with gelfilm
      to provide support for the transplant. The perichondrium was placed under the
      margins of the tympanic membrane and lazed at low power (0.2-1.5 W) in continuous
      mode. In pale tissues, venous blood, methylene blue or fluorescein was used to
      enhance the tissue admittance of laser energy. Surgical failures were linked to
      thermal tissue damage due to excessive energy during lazing. In two cases,
      visibility via microscope into the anterior edge was not complete and the
      transplantant did not adhere in the relatively limited area. One patient had
      epidermal growth under the tympanic membrane and developed local cholesteatoma.
      Laser-assisted myringoplasty provides several advantages over traditional
      myringoplasty: it is minimally invasive, no manipulation of the ossicles is
      needed and it is convenient in anterior perforations, where it can be done
      endoscopically. We prefer a fibre delivery system to a micromanipulator, as
      lazing with endoscopes is possible and thermal damage is easier to prevent.

PMID- 10909003
TI  - Stratum corneum barrier lipids in cholesteatoma.
AB  - Specimens from primary cholesteatomas were examined under the electron microscope
      using a lipid-retaining method that is best suited for intracellular lipids and a
      method that is best for intercellular lipids. In the stratum granulosum of the
      squamous epithelium, a large number of Odland bodies emerged. When the corneocyte
      reaches the transitional stage to the stratum corneum, the Odland bodies
      accumulate near the cell membrane and discharge their contents of lipid and
      enzymes. The lipids are reorganized into multiple long sheets of lamellar
      structures that embrace the keratinized corneocytes, as seen in the formation and
      maintenance of the cutaneous permeability barrier. In this study we draw the
      attention to the facts that the cholesteatoma epithelium is capable of producing
      not only cholesterol, but also several lipids, and that the lipid molecules are
      organized in multilamellar structures in the intercellular space. In theory, the
      failure to desquamate seen in cholesteatomas could be caused by partial or total
      failure of Odland body delivery to the intercellular region, or to local
      breakdown of the permeability barrier.

PMID- 10909004
TI  - Reasons for reperforation after tympanoplasty in children.
AB  - In 116 children and 124 ears with non-cholesteatomatous chronic otitis media
      operated on during a 13-year period from 1968 to 1980 via transcanal
      tympanoplasty and followed with several re-evaluations 15-27 years after
      operation, the causes of reperforation have been analysed. In total, 14 ears
      (11%) had reperformation; in 7 ears (5.6%), the reperforations occurred early
      (during the first 3 months) and in 7 ears late (after 6 months), but most often
      the reperforations occurred after 10 years. The early reperforations were
      presumably failures in surgery. Less experienced surgeons and inflamed, wet
      middle ear mucosa during the primary surgery seemed to be the two most important
      causal factors. Young age at surgery, size and site of the perforation and
      Eustachian tube function seemed to be of no importance for reperforation. The
      early reperforations were closed at surgery and remained closed into adulthood.
      The reasons for late reperforations are less clear; they were presumably caused
      by acute otitis media with perforation in an atrophic part of the drum, which did
      not heal. The reperforations were small, but it was possible to close all of them
      surgically if the patients wanted to be reoperated. It is concluded that
      tympanoplasty, even in young children, is a rewarding option with good and stable
      results.

PMID- 10909005
TI  - Results and experience of 50 cochlear implant operations.
AB  - Cochlear implantation (CI) is a relatively new type of treatment that aims to re
      establish hearing in deaf people. This paper reports on the results from CI
      operations on 34 adults and 17 children. All patients benefited from the
      treatment. The adults' communication with other people improved. Almost all
      patients use their implant 16 h a day and some of them are able to communicate by
      telephone. Among children the results show that the treatment is safe, as no
      complications have developed. Hearing and speech improved in all children, and
      thus also their ability to communicate. The results obtained are dependent on the
      individual patient's condition, the time of operation in relation to the
      development of deafness, and the type of CI used. CI treatment of deaf people may
      be considered to be one of the greatest advances in otology.

PMID- 10909006
TI  - Cochlear implantation and change in quality of life.
AB  - The aim of this study was to assess the benefits of cochlear implantation (CI) in
      adults and to evaluate the average implant usage per day. Ten profoundly deaf
      adults were implanted during the period April 1994 to September 1997. The
      patients answered questionnaires 1 year or more after receiving their cochlear
      implants. All of the patients used their implant daily. The average implant usage
      per day was 16 h. The patients stated that, given the choice, they would again
      opt for a cochlear implant and would recommend a cochlear implant for a deaf
      friend. A paired comparison showed that the implants led to significant
      improvements in a number of factors: self-perceived communication skills,
      frequency of conversation with others, telephone usage, self-confidence and the
      impact of hearing impairments on family life. CI dramatically changed the quality
      of life for all patients. No surgical complications were observed.

PMID- 10909007
TI  - Complications of acute sinusitis in children.
AB  - Acute sinusitis is often a mild, self-limiting disease. However, in some cases,
      especially among children, sinusitis may become a severe, even life-threatening,
      disease. To examine the nature of complications of acute sinusitis, we studied
      the cases of children treated at the Helsinki University ENT Hospital, because of
      a complication caused by acute sinusitis from January 1997 to September 1998.
      There were 12 children (4 girls, 8 boys), whose ages ranged from 16 months to 16
      years. One child had an epidural abscess, one got meningitis and cavernous sinus
      thrombosis, five had orbital cellulitis, one of whom lost her vision permanently
      in one eye, and five had preseptal cellulitis. All the children were treated with
      intravenous antibiotics and all, except the youngest, were treated with a direct
      sinus puncture. An operation (intranasal antrostomy, orbital drainage, functional
      endoscopic sinus surgery or adenoidectomy) was performed on six patients. In the
      majority of children, acute sinusitis is a mild self-limiting disease. However,
      severe complications still exist. When a complication of sinusitis is suspected,
      it is of utmost importance that the child be sent immediately to a hospital for
      proper diagnosis and treatment.

PMID- 10909008
TI  - Functional endoscopic sinus surgery in chronic sinusitis--a series of 237
      consecutively operated patients.
AB  - From 1989 to 1999, 237 consecutive patients with chronic sinusitis and/or nasal
      polyposis entered a prospective study on the effect of functional endoscopic
      sinus surgery (FES). Nasal stenosis associated with massive nasal polyposis was
      the most frequent problem found in 61% of the patients. The rest had long-lasting
      symptoms of chronic sinusitis. Duration of symptoms averaged 9.3 years. Most
      frequent symptoms preoperatively were: nasal stenosis, chronic secretion,
      anosmia, frontal pain, headache and maxillary pain. All patients had the
      operation performed under general anaesthesia. 86% of the patients have been
      operated bilaterally. In 72% the posterior ethmoid was opened, and in 54% the
      sphenoid was opened. The maxillary ostium has been enlarged in 82% of the
      patients and the frontal recess opened in 51% of the cases. No serious
      complications were registered. Annoying bleeding was experienced in 21%,
      hampering the intended procedure. In three patients rhinoliquore was observed.
      One case was treated during the procedure; the last two patients were in no need
      of surgical treatment. At the 1-year follow-up study, 45% of the patients were
      totally satisfied with the results and without symptoms, and 44% were definitely
      feeling better.

PMID- 10909009
TI  - Database developed to record and evaluate computer aided endonasal surgery
      results.
AB  - Computer aided surgery has been used in the Department of Otolaryngology--Head &
      Neck Surgery, Rigshospitalet, Copenhagen since October 1998, and is now a regular
      supplement to conventional functional endonasal sinus surgery (FESS) and
      management of anterior skull base lesions. This technique was designed to enhance
      surgical precision and thoroughness and to reduce complications. Since this is a
      new technique, the clinical findings and surgical outcome are prospectively
      collected in a database. Results for conventional FESS are entered in the same
      database for comparison. The aim of this study is to present a standardized
      Danish database.

PMID- 10909010
TI  - Postoperative infection following nasal septoplasty.
AB  - This retrospective study evaluates the incidence and spectrum of infectious
      complications in 100 consecutive adult nasal septoplasty patients. A total of 12
      patients (mean age 40 years; age range 24-55 years) suffered from postoperative
      infection, and 3/12 had received prophylactic antibiotics. Patients presented
      with abscess formation (n = 7), submucosal swelling and flush (n = 4) and
      haematoma and high fever (n = 1). None of the patients had life-threatening
      complications, such as meningitis, endocarditis or septic/toxic shock. After
      surgical drainage, antibiotic treatment was given orally or intravenously. The
      mean hospitalization time was 3.6 days. To assess the clinical outcome, 8/12
      patients were re-examined about 1.8 years after the operation. They all had an
      improved rhinological status. Septoplasty had been successful in relieving nasal
      obstruction in seven (88%) patients. Staphylococcus aureus was isolated from the
      nasal mucosa in three (38%) patients, which is in line with previous findings in
      healthy nasal septoplasty patients. The use of antimicrobial prophylaxis in
      septal surgery will be discussed.

PMID- 10909011
TI  - Experimental follow-up model for clinical frontal sinus obliteration with
      bioactive glass (S53P4).
AB  - Bioactive glass S53P4 (BG) is an osteoconductive allograft material. Since 1990,
      BG has been used in the obliteration of frontal sinuses in more than 30
      consecutive patients. The patients have been monitored regularly with clinical
      examinations, computer tomography (CT) scans, laboratory tests and, in a few
      cases, biopsies have also been obtained. The material has been well tolerated and
      no loss of volume of obliteration material has been seen in the obliterated
      sinuses. However, in repeated CT monitoring and with Region of Interest (ROI)
      analysis, a decrease in the density of the obliteration material inside the
      frontal sinuses has been seen. In the present study, the clinical conditions
      after an obliteration operation were simulated and the behaviour of the BG in the
      obliterated area was observed. The aim was to study whether it is possible
      indirectly to estimate the resorption of a massive amount of BG with ROI analysis
      for monitoring the clinical success of the treatment. Thus two sizes of granules
      (0.63-0.8 mm and 0.8-1.0 mm) in eight separate BG amounts, weight 25 g, were
      tested in simulated body fluid (SBF) in standard conditions. The dissolution of
      silicon (Si) and phosphate (P) was detected with direct plasma atom emission
      spectroscopy (DCP-AES) monthly up to 6 months. The BG amounts were scanned with
      CT and the slices analysed using the ROI technique at 1, 3 and 6 months. The
      cumulative loss of Si and P in SBF was significant during the study (p < 0.0001)
      and it was stronger with smaller than with larger granules (p < 0.0001). This was
      shown correspondingly by the decrease of Hounsfield units (p < 0.0001) in ROI
      analysis. The method seems reliably to reveal the resorption of BG for clinical
      purposes.

PMID- 10909013
TI  - Eight years of follow-up--uvulopalatopharyngoplasty combined with midline
      glossectomy as a treatment for obstructive sleep apnoea syndrome.
AB  - In 22 patients with obstructive sleep apnoea, uvulopalatopharyngoplasty was
      combined with a midline glossectomy of the dorsum of the tongue. The body mass
      index (BMI) was normal in 13 cases and abnormal in 9. Daytime polysomnography was
      performed in all cases both preoperatively and 1 year postoperatively. In 16
      patients another daytime polysomnography was performed after 8.4 years. The
      patients also answered a questionnaire 11, 33, 43 and 98 months postoperatively.
      The apnoea index (AI) was reduced in 82% of cases 12 months postoperatively,
      being reduced by 50% in 59% of cases and normalized in 32%. After 8.4 years a
      reduction in the AI was found in 75% and a normal AI in 25% of patients.
      Subjectively speaking, 95% of the patients were satisfied with the operation at
      the first follow-up, and the figure was 86% at the fourth follow-up; 64% did not
      suffer from sleep apnoea at the first follow-up as compared with 46% at the
      latest follow-up. There was an increase in subjective symptoms postoperatively
      until the third follow-up. After that the symptoms became stable. There were no
      immediate postoperative complications, and only minor long-term problems. The
      duration of postoperative care at the hospital was 2 days. No relationship was
      found between BMI and outcome.

PMID- 10909012
TI  - Vascular permeability factor/vascular endothelial growth factor in nasal polyps.
AB  - Although the aetiology of polyps is still, for the most part, unknown, the
      disease is known to involve tissue oedema. Vascular permeability/vascular
      endothelial growth factor (VPF/VEGF) is a major inducer of angiogenesis and
      capillary permeability. This study investigated VPF/VEGF expression in biopsies
      of nasal polyps from 39 patients and in healthy nasal mucosa from 10 patients by
      immunohistochemical staining. Staining for VPF/VEGF in the mucosal surface and in
      the glandular epithelium of nasal polyps was weaker than in normal controls. In
      two patients, strong staining for VPF/VEGF was found in a granular pattern in
      mast cells, while the mast cells in other polyposis patients appeared to be
      largely degranulated. VPF/VEGF was not seen in the mast cells of control
      patients. Although expression of VPF/VEGF was not increased in the epithelium of
      the nasal polyps, VPF/VEGF secreted from mast cells may take part in nasal polyp
      formation.

PMID- 10909014
TI  - Does the oral device Noiselezz prevent sleep apnoea?
AB  - Both snoring and apnoea are caused by the collapse of soft tissue in the upper
      airways during sleep. Increasing the cross-sectional area of the airways in these
      segments by moving the mandible and/or the tongue forward stabilizes the upper
      airways in obstructive sleep apnoea syndrome (OSAS) patients. The aim of this
      study was to determine the effect of Noiselezz, which is an oral appliance of the
      mandibular advancing type, designed for easy use. Twenty-one patients, all men
      (aged 50.6 +/- 10.4, body mass index 26.5 +/- 3.3) were included in the study.
      Polysomnography (PSG) was performed before the patients started using Noiselezz.
      After a period of 2 weeks accustomizing to the oral device, the patients had
      another PSG performed with Noiselezz inserted. We found no significant
      differences in total sleep time, percentage of time spent snoring, duration of
      rapid eye movement (REM) sleep, slow-wave sleep, inter-sleep wake and sleep
      efficiency, apnoea/hypopnoea index (AHI) or lowest measured oxygen saturation
      after apnoea (minSaO2). No significant differences were found in the localization
      of obstructions or intrathoracal inspiratory pressure with and without the use of
      the Noiselezz oral device. Three patients (14%) reported satisfaction with
      treatment by the oral device. All three continued to use Noiselezz as treatment.
      The rest of the patients (86%) either did not tolerate the device at all or tried
      it for a period and then requested alternative treatment (n = 12). Most patients
      found the oral device "Noiselezz" inconvenient to use, and our results show that
      the device has little or no effect on snoring and sleep apnoea.

PMID- 10909015
TI  - Computational simulation of accumulation of expired air in the infant cot.
AB  - Accumulation and re-breathing of CO2 in expired air has been suggested as one
      possible explanation for the strong association between prone sleeping position
      and sudden infant death syndrome (SIDS). This preliminary study applying a modern
      computational fluid dynamics (CFD) program to simulate the aerodynamics in an
      infant cot supports the idea that accumulation of expired air may occur in the
      prone position. The literature dealing with the potential association between re
      breathing of accumulated CO2 and SIDS is briefly reviewed.

PMID- 10909016
TI  - Necrotizing fascitis of the head and neck--report of three cases and review of
      the literature.
AB  - Necrotizing fasciitis (NF) of the head and neck is a rare but potentially life
      threatening soft tissue infection primarily affecting the superficial fascial
      planes. It is caused by group A streptococci or by a synergistic combination of
      aerobe and anaerobe micro-organisms. If proper treatment is delayed, the
      infection may cause extensive necrosis of overlying skin, extend to deeper planes
      and produce severe systemic toxicity. Recent reviews suggest that cervical and
      facial NF should be considered separate clinical entities with different clinical
      features and prognosis. In both, early diagnosis with prompt, aggressive surgical
      and medical treatment is essential to a successful outcome. Three cases of NF of
      the neck secondary to peritonsillar/parapharyngeal infections are presented and
      the main characteristics of 117 well-characterized cases of cervical and facial
      NF are reviewed.

PMID- 10909017
TI  - Complaints and satisfaction after uvulopalatopharyngoplasty.
AB  - A questionnaire administered 2 years after classical laser
      uvulopalatopharyngoplasty (UPPP) showed that 42% of 69 patients had complaints.
      Most of the complaints, however, were comparatively minor. The most frequent
      complaint was a tendency to nasal regurgitation (13%), although only two patients
      needed treatment. Other complaints were pharyngeal hypersecretion (10%),
      swallowing problems (9%) and speech disturbances (7%). Fourteen per cent of the
      69 patients were not satisfied with the effect of the operation. In the group
      with complaints, 25% were dissatisfied with the result of the operation, whereas
      only 8% of those with no complaints were dissatisfied (p < 0.05). Continued
      snoring after UPPP was closely correlated to dissatisfaction with the general
      result (p < 0.01). It is very important to carry out follow-up after UPPP because
      complaints and dissatisfaction are common. Every effort should be made to reduce
      the tendency to nasal regurgitation. The results are relatively good and the
      procedure justified in cases of severe snoring and continuous positive airway
      pressure (CPAP)-resistant obstructive sleep apnoea (OSA). The severity and number
      of complaints were found to be acceptable in this difficult treatable entity.

PMID- 10909018
TI  - Basic fibroblast growth factor (bFGF) in saliva--physiological and clinical
      implications.
AB  - Basic fibroblast growth factor (bFGF) has significant properties in wound
      healing, tissue regeneration and ulcer repair of the upper digestive tract. The
      purpose of the present study was to identify and analyse factors affecting the
      concentration of bFGF in saliva from healthy human individuals. A commercially
      available enzyme-linked immunosolvent assay kit (ELISA) was used for the analyses
      of bFGF in saliva. In total, 56 samples were collected from 28 healthy subjects,
      15 male and 13 female. Determination of bFGF was performed by spectrophotometer
      (wavelength 490 nm). bFGF was detected in all samples. Mean bFGF concentration
      was 0.87 pg/ml (SD 0.49) and the concentration ranged from 0.3 to 1.9 pg/ml. In
      subjects aged 22 to 49 years, no age-dependent variation in bFGF was present,
      females did not differ from males, and no difference was evident between European
      and Asian subjects. Smokers had significantly higher saliva concentrations of
      bFGF than non-smokers. Since bFGF, together with other growth factors, is
      involved in wound healing and tissue repair, we suggest that bFGF in saliva is
      involved in the reparative processes of mucous membranes.

PMID- 10909019
TI  - Paediatric otolaryngology--disease profile and characteristics of children in
      outpatient surgery.
AB  - Data were collected from 178 consecutively operated children during a 6-week
      period at an Oslo hospital in order to study disease profile and routines for
      referral and treatment in outpatient otorhinolaryngologic surgery. Median time
      from referral to surgery was less than 4 months. The majority of the children
      subjected to operation for recurrent acute otitis media, tonsillitis or upper
      respiratory infections had suffered from the disease for 12 months or less.
      Obstructive symptoms were registered in 18% of the children. Hospital referrals
      and controls came mainly from ENT (ear, nose and throat) specialists or
      paediatricians. Significantly more boys were subjected to surgery. Median age at
      the time of surgery was 4.2 years, and there was an equal distribution of
      pharyngeal and middle ear surgery. The numerous combinations of middle ear
      surgery reflect the non-specific treatment guidelines for otitis media.

PMID- 10909020
TI  - Paediatric otolaryngology--a parental satisfaction study in outpatient surgery.
AB  - A parental satisfaction survey was administered to obtain information as to
      exactly how patients and their parents experience essential aspects of their
      treatment. The parents of 178 children who underwent ear, nose and throat (ENT)
      surgery completed a questionnaire on various aspects of treatment satisfaction
      during a 6-week period. Most of the respondents expressed overall satisfaction
      with the treatment. The factor analysis revealed three parental satisfaction
      factors. Accordingly, we interpreted the subscales as i) surgical staff and
      general treatment satisfaction, ii) nursing staff and general information
      satisfaction and iii) anaesthetic staff satisfaction. The internal consistency
      values of the subscales, as measured by Cronbach's alpha coefficient, were 0.86,
      0.84 and 0.71, respectively. The three scores were mutually correlated; this
      correlation was significant (0.46-0.67). The duration of general anaesthesia and
      demographic factors had a small, but significant impact on the satisfaction
      subscores. In conclusion, the satisfaction study encourages improvement in the
      evaluation and administration of treatment.

PMID- 10909021
TI  - Bacteriology of the tonsil core in recurrent tonsillitis and tonsillar
      hyperplasia--a short review.
AB  - In recurrent tonsillitis, the tonsil core harbours numerous bacteria, some of
      which are pathogenic and may occur in great numbers. The most frequent bacteria
      are Haemophilus influenzae, followed by Staphylococcus aureus and Streptococcus
      pyogenes. A high tissue concentration of these bacteria correlates with clinical
      parameters of infection and hyperplasia of the tonsils. The role of Streptococcus
      pyogenes, while undisputed in acute and epidemic tonsillitis, should perhaps be
      re-evaluated in recurrent and/or hyperplastic tonsillitis.

PMID- 10909022
TI  - Methods of haemostasis in tonsillectomy assessed by pain scores and consultation
      rates. The Roskilde County Tonsillectomy Study.
AB  - OBJECTIVES: To compare four methods of haemostasis after tonsillectomy assessed
      by pain scores and consultation rates. STUDY DESIGN AND METHODS: A prospective
      study. The method of sole compression of the tonsillar fossae with gauze tampons
      was compared to ligation, bipolar diathermy and ligation/diathermy in
      combination. RESULTS: Highly significantly lower pain scores after discharge were
      found in the compression group compared to the other three groups (p < 0.025).
      The consultation rate in person after discharge of the compression group was
      significantly lower than in the diathermy group (p < 0.01) and the
      ligation/diathermy group (p < 0.05). CONCLUSION: Sole compression was associated
      with considerably less morbidity and no higher risk of postoperative haemorrhage.
      Sole compression should therefore be preferred in tonsillectomy whenever the
      surgeon considers it to be justified.

PMID- 10909023
TI  - Persistence of Lactobacillus plantarum DSM 9843 on human tonsillar surface after
      oral administration in fermented oatmeal gruel. A pilot study.
AB  - The occurrence of Lactobacillus plantarum DSM 9843 on tonsillar scrapings was
      studied after single-dose administration. Six healthy volunteers gargled 100 ml
      of fermented oatmeal gruel containing 2 x 10(11) colony forming units (cfu) of
      Lb. plantarum DSM 9843 for 2 min and then swallowed it. Two healthy volunteers
      drank 50 ml fermented oatmeal gruel (containing 1 x 10(11) cfu of Lb. plantarum
      DSM 9843) mixed with 50 ml fruit juice, and in another experiment, 5 ml fermented
      oatmeal gruel (containing 1 x 10(10) cfu of Lb. plantarum DSM 9843) mixed with 95
      ml fruit juice. Lb. plantarum DSM 9843 were found in tonsillar scrapings 4-8 h
      after intake of 2 x 10(11) cfu, for 5-8 h after intake of 1 x 10(11) cfu, and
      finally up to 4 h after intake of 1 x 10(10) cfu. On electron microscopy
      micrographs, short rod-shaped bacteria were visible 1 h after intake of the
      fermented oatmeal gruel, but not 2 h after intake. The results suggest that Lb.
      plantarum DSM 9843 possess an ability to adhere to tonsillar cells.

PMID- 10909024
TI  - Choanal adenoid syndrome--a preliminary report.
AB  - A series of 19 patients with long-lasting nasal stenosis despite repeated
      treatment attempts, including, in many cases, repeated adenoidectomy, was found
      to have ectopic adenoid tissue inside the choanae. The choanal adenoid tissue
      could not be removed by curettage, only transnasally using forceps. The treatment
      was successful in all 19 patients. It is estimated that in at least 2% of the
      patients with long-lasting nasal stenosis, attention should be focused on the
      bottleneck of the nasopharyngeal airway represented by the choanae, primarily by
      fibre optic endoscopic examination.

PMID- 10909025
TI  - Treatment of cricopharyngeal dysfunction by endoscopic laser myotomy.
AB  - Cricopharyngeal dysfunction may be caused by a central or peripheral nerve
      disease, a muscular disease, previous neck surgery or it may be idiopathic. The
      treatment may be a myotomy of the cricopharyngeal muscle carried out externally
      or endoscopically. Since 1995 we have treated 17 patients with endoscopic myotomy
      of the cricopharyngeal muscle with the CO2 laser. Anamnesis was the basis for the
      diagnosis and we obtained further information from videoradiographs of the upper
      gastrointestinal tract and from manometry. There were no immediate or late
      complications from the surgery. Three patients died from other diseases, the
      remaining 14 patients were sent a follow-up questionnaire and asked to grade
      their complaints pre- and postoperatively and to answer questions about their
      weight. All patients except one stated that their swallowing abilities had
      improved since the surgery and more than half of the patients had gained weight.
      A low rate of complications and postoperative morbidity, combined with good
      functional results, indicate that endoscopic laser myotomy should be recommended
      for treatment of cricopharyngeal dysfunction.

PMID- 10909026
TI  - Diagnostic aspects of dysphagia.
AB  - Swallowing problems are common, with a prevalence of 5-30% in different
      populations. Clinical work-up must start with a careful evaluation of the
      symptomatology, which should then lead to appropriate investigations. A crucial
      point in the evaluation of these patients is the comparison between the patient's
      symptoms and the findings during the examination. Symptoms and findings often do
      not match, or incidental endoscopic or manometric findings are taken as an
      indication for treatment. This review tries to elucidate this relationship.

PMID- 10909027
TI  - pH monitoring in patients with benign voice disorders.
AB  - The aim of this study was to compare oesophageal pH-metry with laryngeal signs
      and symptoms in patients suspected of laryngeal reflux disease. A total of 60
      patients with voice disorders, who were suspected of laryngeal reflux, were
      tested by single probe oesophageal pH monitoring. Thirty-two suffered from reflux
      laryngitis. A comparison of symptoms in patients with proven reflux to patients
      with no reflux was made. The symptoms were more frequent in the patients in the
      reflux group than in the non-reflux group. There was a significant difference
      between the groups with regard to dysphonia, sore throat, thick mucus and
      heartburn. Clinical signs appeared more frequently in the reflux group than in
      the non-reflux group. A significant difference was found between the groups
      regarding oedema of the vocal cords and hyperaemia and oedema of the posterior
      commisure, contact granuloma, posterior wall granulation and increased muscle
      tension. The patients in the reflux group were given medical treatment using
      omeprazole, and 76% logopedic voice training program. More than 50% of the
      laryngeal reflux patients were treated for more than 4 months before their voice
      problems had resolved. It is important to realize that signs of reflux laryngitis
      are not confined to the posterior commisure.

PMID- 10909028
TI  - Endoscopic CO2 laser therapy of Zenker's diverticulum--experience from 61
      patients.
AB  - Endoscopic laser resection of hypopharyngeal diverticula has been used in the ENT
      Department, Odense, Denmark, since 1989. The outcome of treatment is reported in
      this presentation. Of the 61 patients, 32 (52%) were males. Age at operation was
      72 years (median), range 37-94 years. The diagnosis in all patients was confirmed
      by barium radiography of the hypopharynx and the oesophagus. A Benjamin-Hollinger
      diverticuloscope was used for viewing the tissue bridge separating the
      diverticulum and the oesophagus. The tissue bridge was cut from the apex to the
      base using a CO2 laser. Perioperative complications were seen in 6 patients:
      Bleeding (1), subcutaneous emphysema without (3) or with (1) inflammation,
      inflammation without emphysema (1). The duration of postoperative nasogastric
      feeding was 2 days (median) (range 1-11 days). Fifty-four patients received
      prophylactic antibiotic treatment for a median of 3 days (range 0.5-13 days). The
      duration of postoperative hospitalization was 3 days (median) (range 2-14 days).
      The patients were routinely examined 2-3 months postoperatively. There were
      recurrences in 6 patients (10%), all successfully re-operated. A follow-up
      questionnaire was sent to patients who had finished their postoperative
      examination in March 1999. All 37 patients still alive responded. Median follow
      up time was 37 months (range 3-96 months). Two patients reported recurrence at
      the time of follow-up and have been successfully re-operated. Eight patients
      reported minor and intermittent symptoms that did not indicate further
      evaluation. We conclude that laser resection of hypopharyngeal diverticula is an
      efficient therapy, which is applicable to and well tolerated in the great
      majority of patients. The rate of recurrence is low and re-operation can be
      performed without difficulty.

PMID- 10909029
TI  - Zenker's diverticulum treated by the endoscopic stapling technique.
AB  - The objective of the present study is to determine whether the endoscopic
      stapling technique for the treatment of Zenker's diverticulum provides a relief
      of symptoms and an acceptably low number of complications. Previous studies have
      indicated that endoscopic stapling of the common wall between the oesophagus and
      the diverticulum is a safe and effective method that has a low complication rate
      and only necessitates a few days of hospitalization. To the present only a few
      investigations including a limited number of patients have reported the clinical
      outcome with regard to relief of symptoms and degree of satisfaction in a group
      of patients treated with this new approach. Twenty-three consecutive patients
      with Zenker's diverticulum treated with endoscopic staple-assisted
      oesophagodiverticulotomy were investigated. The median age was 70 years and the
      median observation time was 12 months. All patients but one (96%), reported
      significant relief of symptoms and 76% had no symptoms at all at the time of
      follow-up. In one patient, a postoperative episode of uncomplicated fever
      occurred, which was managed successfully with gastric tube and antibiotics. Most
      patients resumed oral intake of fluids and foods within the first postoperative
      day. The high degree of patient satisfaction, the low rate of complications and
      the few recurrences of symptoms reported in the present study indicate that the
      endoscopic stapling technique is an efficient and reliable treatment for Zenker's
      diverticulum.

PMID- 10909030
TI  - Longitudinal oesophageal muscle and pharyngo-oesophageal dysphagia--a deductive
      study.
AB  - The hypothesis has been raised that a dysfunction of the longitudinal oesophageal
      muscle is the common denominator for pharyngeal and oesophageal dysphagia in
      patients with hiatal hernia, and that contraction of the longitudinal muscle is a
      contributing factor for the opening of the upper oesophageal sphincter and for
      the stiffening of the oesophageal wall when swallowing. Different studies were
      used to test the implications of this hypothesis. It was concluded that
      dysfunction of the longitudinal oesophageal muscle, caused by slipping of the
      distal end through the hiatal canal, can explain oesophageal dysphagia and
      inadequate opening of the upper oesophageal sphincter.

PMID- 10909031
TI  - Cortical networks subserving the perception of tinnitus--a PET study.
AB  - Subjective tinnitus is an auditory phantom perception that may arise from any
      aberrant signal within the auditory system. Further processing of this signal and
      the conscious perception of tinnitus takes place in the cerebral cortex. A few
      functional brain-imaging studies have been performed to elucidate the underlying
      cerebral mechanisms of this perception. These studies mostly concern rare types
      of tinnitus (e.g. tinnitus changeable by oral-facial movements), or compared
      tinnitus patients with healthy volunteers. These studies attributed variable
      activation of the primary auditory cortices, associative auditory cortices and
      the left hippocampus to the perception of tinnitus. Based on these heterogeneous
      results, no consensus on the underlying mechanisms has been reached. The aim of
      the present study was to obtain further details of the central perception and
      processing of the tinnitus signal. Positron emission tomography (PET) was used to
      map the tinnitus-specific central activity. By contrasting PET-images of
      suppressed tinnitus with PET-images of the habitual tinnitus sensation, we were
      able to identify a right prefrontal-temporal network associated with the
      perception of tinnitus. Besides the evidence of activation of associative
      auditory sensory regions, the results indicated that activation of cortical
      centres subserving attention and emotion may underlie the continuous irritability
      associated with severe tinnitus.

PMID- 10909032
TI  - Primary speech restoration at laryngectomy by insertion of voice prosthesis--10
      years experience.
AB  - A total of 88 patients underwent laryngectomy at the ENT Department, Gentofte
      University Hospital, Hellerup, Denmark, from May 1989 to May 1999. Of these, 85
      patients underwent salvage operations for squamous cell laryngeal carcinoma after
      previous full course radiotherapy. A total of 76 patients had primary tracheo
      oesophageal puncture performed at the time of laryngectomy, 11 had a secondary
      procedure performed, 7 of these had been laryngectomized elsewhere. Eight
      patients were not eligible for tracheo-oesophageal puncture due to age, social
      reasons or extensive surgery. In all, 79 patients were able to use the prosthesis
      for communicative purposes weeks after the operation and developed fluent speech.
      During the observation time, 14 patients had their voice prosthesis removed or
      disconnected for various reasons. The average life duration for Provox voice
      prosthesis generation I vs Provox generation II was 3.1 and 2.3 months,
      respectively.

PMID- 10909034
TI  - Cystic hygroma of the head and neck--a long-term follow-up of 44 cases.
AB  - Cystic hygroma of the neck is a relatively rare congenital malformation usually
      diagnosed during the first years of infancy. Complete surgical extirpation may be
      impossible without sacrificing important neurovascular structures. This paper
      reports the long-term outcome of surgical treatment during a 35-year period. A
      follow-up examination of 44 patients (24 males and 20 females) treated in our
      departments during the last 35 years was performed. Median age at first operation
      was 1.5 years (0-28 years) The observation period ranged between 1 and 36 years,
      median 16.2 years. Indications for operation were space occupying lesion,
      haemorrhage, dysphagia, difficulties in pronunciation or breathing and infection
      or nerve lesions. Fifty percent of the patients revealed residual or recurrent
      hygroma at the time of follow-up. Forty-four percent suffered from impaired
      speech, food intake, breathing or swallowing. Thirty-six percent were
      cosmetically bothered, and only 11% reported reduced quality of life. A
      significant correlation was noted between the extension of the lesion and (i) the
      number of operations performed and (ii) the rate of recurrent or residual
      hygroma. The rate of residual or recurrent hygroma was statistically higher for
      the suprahyoid lesions compared with the infrahyoid lesions. The localization and
      extent of the lesion is related to the surgical outcome. Surgical intervention
      should be centralized and should be considered carefully. Neurovascular
      structures should not be damaged in an attempt to effect complete removal. The
      above-mentioned results lead to a search for a new therapeutic modality, and the
      authors have recently taken up the Japanese way of treating hygromas by
      intralesional injection of OK-432. The first two patients treated by this
      technique had total regression of the lesion, and the method seems to be
      promising as an alternative to surgery.

PMID- 10909033
TI  - Oral cancer--results of treatment in the Copenhagen University Hospital.
AB  - During the period 1992-96, 304 patients with malignant tumours of the oral cavity
      were referred to the Department of Head & Neck Oncology, Copenhagen University
      Hospital. The female:male ratio was 1:2. Age ranged between 20 and 96 years,
      median 61 years. Ninety-five percent of the tumours were squamous cell
      carcinomas. Twenty-two percent were in stage I, 21% were in stage II, 21% were in
      stage III and 36% were in stage IV. Sixty percent of the patients underwent
      primary surgical resection, combined with reconstructive procedures if necessary.
      In 39% of all cases, surgery was followed by radiotherapy, while 21% of the
      patients, mainly stage I and II patients, were only treated surgically.
      Radiotherapy alone was received by 36% of the patients, mainly stage III and IV.
      Four percent of the patients received no treatment due to advanced disease or
      general poor condition. The overall recurrence rate was 42%, ranging from 23% in
      stage I to 61% in stage IV. Thirty-eight percent of these patients were treated
      for recurrence, almost exclusively by surgery. The survival rate 1 year after
      treatment of recurrence was 90%, 60% and 50% for patients in stage I, II and III
      respectively, while only 1 of 16 patients in stage IV was alive after 1 year.
      Three-year crude survival for the whole material was 42%, ranging from 58% in
      stage I to 18% in stage IV. This is an improvement of 12% compared with a similar
      group of patients treated in our departments in the period 1978-82, when the
      primary treatment of choice was external irradiation. The survival rate was, as
      expected, closely related to T- and N-stage at time of diagnosis. In conclusion,
      we recommend primary surgery followed by irradiation therapy for patients in
      stages II, III and IV. Surgical treatment of recurrence in patients who were
      formerly treated by irradiation therapy should be reserved for patients in good
      general condition and in a low TNM stage, stage IV patients will only benefit
      from salvage surgery in a few exceptional cases.

PMID- 10909035
TI  - Surgical outcome in malignant parotid tumours.
AB  - Of 494 parotid gland tumours treated in Copenhagen county (population 600,000
      inhabitants) in the period 1986-95, 50 patients (34 males, 16 females) had
      tumours that were proven to be malignant, making an incidence of
      0.62/100,000/year. The patients age ranged from 14 to 87 years, mean 64 years.
      According to the UICC classification system, 6 tumours (12%) were classified as
      stage I, 23 (46%) as stage II, 14 (28%) as stage III, and 7 (14%) as stage IV.
      The material included 41 primary parotid gland tumours, histologically the
      tumours were verified as mucoepidermoid carcinoma (n = 13), adenocarcinoma (n =
      9), squamous cell carcinoma (n = 6), carcinoma ex pleomorph adenoma (n = 3),
      acinic cell carcinoma (n = 3), adenoid cystic carcinoma (n = 3) and other
      histological diagnoses (n = 4). Primary malignant lymphoma of the parotid gland
      was diagnosed in six tumours and the last three tumours were metastatic
      carcinoma. Four therapeutic modalities were applied: surgery only, surgery +
      radiation, surgery + chemotherapy, and surgery + chemotherapy + radiation.
      Surgical radicality was achieved in 76% and radicality was unrelated to tumour
      histology. Normal or nearly normal facial nerve function (HB1&2) was noted at
      last follow-up in 60%. Five-year crude survival for all patients was 68%.
      Survival was not dependent on N-classification. Patients in stage I had a better
      survival than did patients in stages II, III and IV. No significant difference
      was observed in 5-year crude survival or in the post-operative facial nerve
      function between the radically operated patients (n = 38) and patients with
      residual tumour (p = 0.27, Log-rank test), (p = 0.48, chi 2 test).

PMID- 10909036
TI  - Changes in blood flow in the epigastric free flap after microsurgical artery
      anastomoses in rats.
AB  - A number of clinical disorders of free vascularized flap are presumed to reflect
      insufficient blood flow (BF) or an inadequate range of vascular responsiveness.
      We compared the changes in BF in a pedicled and free epigastric flap, directly
      after and 90 min after performing microsurgical artery anastomoses. We used the
      clamping method and laser Doppler flowmetry in six Sprague-Dawley rats. The BF
      response curves shortly after re-anastomosing of the artery differ markedly from
      those in a pedicled flap model and curves registered 90 min after performing the
      anastomosis. We conclude that the clamping method is reliable and reproducible
      when studying the short-term autoregulatory BF patterns of epigastric pedicled
      and free flaps.

PMID- 10909037
TI  - Regulation of mast cell number and function.
AB  - Mast cells are complex, multifunctional cells that have unique phenotypes and
      growth requirements. Regulation in vitro of human mast cell growth and function
      differs from regulation of rodent mast cells. Human cell yields in vitro vary
      depending on tissue of origin, use of mononuclear or CD34+ progenitor cells,
      presence of cytokines, and serum-free versus serum-containing mediums. This
      article presents a summary of recent advances in the understanding of cytokine
      regulation of mast cell numbers and function in rodents and humans.

PMID- 10909039
TI  - Mastocytosis and the skin.
AB  - The most frequent site of organ involvement in individuals with any form of
      mastocytosis is the skin. Cutaneous lesions include urticaria pigmentosa,
      mastocytoma, diffuse and erythematous cutaneous mastocytosis, and telangiectasia
      macularis eruptiva perstans. The major histologic feature is an increase in the
      number of mast cells in the dermis. Treatment depends on the type of skin
      lesions.

PMID- 10909038
TI  - Kit signal transduction.
AB  - The current understanding of kit signaling is that a limited number of signaling
      proteins interact to build multiple interacting networks that allow diverse
      cellular responses. Cytoplasmic signaling proteins are increasingly seen to form
      networks directed through converging and interacting pathways rather than
      following a simple linear model. There are also numerous cross-connections
      between signaling proteins more distal to the receptor. Ras thus binds PI3 kinase
      and potentiates its activation, whereas the Rac-dependent protein kinase PAK
      phosphorylates MEK and thereby stabilizes its association with Raf. A signaling
      network with multiple intersecting pathways can obtain a single, coherent
      response from numerous, potentially conflicting signals. There is still limited
      information about the effect of activating mutations on various aspects of kit
      signaling. There is, however, mounting evidence that an activating mutation may
      enhance kit signaling and also induce factor-independent activation of kit. For
      instance, this activation could occur through degradation of SHP-1, the protein
      tyrosine phosphatase that negatively regulates kit signaling. There is also
      emerging evidence that inherent inhibitory factors may exist in the juxtamembrane
      of kit and may be suppressed as a result of a mutation in that region.
      Understanding the impact of these activating mutations on kit signaling is
      important, not only in contributing to the understanding of the pathogenesis of
      mastocytosis but ultimately in forming the basis for more effective therapeutic
      intervention in this disease.

PMID- 10909040
TI  - Hematologic aspects of systemic mastocytosis.
AB  - Systemic mast cell disease is characterized by bone marrow involvement by mast
      cells and frequently by peripheral blood cytopenias. The coexistence of
      hematologic disorders, such as myeloproliferative or myelodysplastic syndromes,
      or of lymphoreticular malignancies with SMCD is common. Overt mast cell leukemia
      is rare. In general, patients who coexhibit a severe hematologic disorder tend to
      have a more compressed clinical course and a worse prognosis. Hemorrhage can be a
      result of heparin release from stimulated mast cells.

PMID- 10909041
TI  - Lymphoid tissues and the immune system in mastocytosis.
AB  - The association of mast cells and lymphoid tissues may reflect either regional
      overproduction of growth factors for mast cells or a predisposition for mast
      cells at certain sites within the body, particularly the liver, lymph nodes, and
      spleen. The significant increase in mast cell number associated with mastocytosis
      is not sufficient to generate a change in either T-cell or B-cell functions, as
      evaluated by analyzing cytokine phenotype or immunoglobulin production,
      respectively, nor to expose these patients to infections or allergic diseases.
      Mast cells in mastocytosis cannot be said with certainty to be "normal" in all
      respects, however, and the failure to identify an effect of mast cells on either
      B-cell Ig production or T-cell cytokine profiles cannot be taken as absolute
      evidence that mast cell products have no influence on lymphocyte function,
      particularly at the local tissue level.

PMID- 10909042
TI  - Gastrointestinal abnormalities and involvement in systemic mastocytosis.
AB  - Recent studies have shown that involvement of the gastrointestinal tract is much
      more frequent than originally reported in patients with systemic mastocytosis.
      Seventy percent to 80% of patients with systemic mastocytosis are found to have
      gastrointestinal symptoms when a careful history is taken, and abnormalities in
      the gastrointestinal tract are frequently detected by endoscopic studies,
      functional studies of absorption, and barium studies. Because of the rarity of
      the disease, there are few prospective studies of gastrointestinal involvement,
      so the actual frequency of upper and lower gastrointestinal lesions is unknown.
      Furthermore, there have been no studies correlating endoscopic abnormalities of
      the lower gastrointestinal tract with the presence or absence of diarrhea, which
      is a frequent symptom (mean, 43% [range 14%-100%]). A review of gastric acid
      studies reveals that a proportion of patients develop gastric acid hypersecretion
      because of the hyperhistaminemia, which can result in ulcer disease that in turn
      can cause dyspeptic pain, small intestinal mucosal damage, and malabsorption. In
      some patients gastric acid hypersecretion in the range seen in Zollinger-Ellison
      syndrome can develop. A number of studies suggest that the prevalence of peptic
      ulcer disease has been underestimated in these patients and is certainly higher
      than the general population. The exact physiologic basis for the diarrhea or
      nondyspeptic abdominal pain remains largely unknown in these patients. Whereas
      some studies suggest small intestinal mucosal abnormalities are responsible for
      most cases of malabsorption not associated with gastric acid hypersecretion, this
      supposition also remains unproven. Hepatomegaly, portal hypertension,
      splenomegaly, and ascites occur frequently in patients with systemic
      mastocytosis, especially those with category II through IV disease. Whereas the
      histology of the liver and spleen and alterations in hepatic function studies
      have been well studied, the pathogenesis of each of these abnormalities has not
      been well studied, and almost all the information comes from a few well-studied
      case reports.

PMID- 10909043
TI  - Pediatric mastocytosis.
AB  - Pediatric mastocytosis presents with heterogeneous cutaneous lesions and symptoms
      that are caused by increased numbers of tissue mast cells. In contrast with adult
      patients with mastocytosis, the course of pediatric patients is usually
      transient. Therefore, it has long been speculated that pediatric and adult
      mastocytosis may be based on different pathogenetic mechanisms. Indeed, new
      genetic findings now indicate differences in the pathogenesis. Adult patients
      usually express activating mutations of the growth factor receptor c-kit. Most
      children lack these mutations but sometimes carry other inactivating mutations of
      c-kit. Only children with progressive mastocytosis seem to express the activating
      mutations seen in adults. Causal treatment is not yet available, but H1 and H2
      antihistamines may provide relief of symptoms. It is important to counsel
      patients and their parents carefully to avoid triggers that induce systemic mast
      cell degranulation.

PMID- 10909044
TI  - Serum tryptase and the laboratory diagnosis of systemic mastocytosis.
AB  - Total tryptase levels of 20 ng/mL or higher in a baseline serum sample when the
      ratio of total to beta-tryptase is 20 or greater strongly suggest underlying
      systemic mastocytosis. Whether these criteria prove to be more sensitive than a
      bone marrow biopsy will require further study. Although the absolute level of
      total tryptase does not predict disease severity, it may provide a practical
      method for assessing the efficacy of therapeutic interventions designed to reduce
      the mast cell burden.

PMID- 10909045
TI  - Treatment of systemic mast cell disorders.
AB  - The heterogeneous nature of disease manifestations in mastocytosis requires the
      individualization of therapy to each patient's clinical presentation and
      prognosis. The mainstay of treatment for most categories of mastocytosis are H1
      and H2 antihistamines with the addition of corticosteroids for more severe
      symptoms. This article presents a summary of treatment strategies for indolent
      and aggressive forms of mastocytosis along with a discussion of future
      therapeutic directions.

PMID- 10909046
TI  - New approaches to therapy for mastocytosis. A case for treatment with kit kinase
      inhibitors.
AB  - Some forms of mastocytosis are caused by c-kit mutations which cause constitutive
      activation of kit kinase. Compounds that inhibit kit kinase, such as indolinones,
      are therefore attractive as potential therapeutic agents. A hierarchy exists in
      the ability of compounds to inhibit kit kinase effectively. Some compounds can
      inhibit ligand-induced activation of wild-type receptor but are ineffective
      against constitutively activated mutants. Other compounds can inhibit ligand
      induced activation of wild-type kit and ligand-independent activation by
      juxtamembrane domain mutations but not activation by activation loop mutations.
      Still others effectively inhibit wild-type kit and constitutively activated kit
      bearing either juxtamembrane or kinase domain mutations and kill the neoplastic
      mast cells expressing these mutants. No therapy currently exists that
      specifically targets a cause of mastocytosis, but there are good reasons to
      believe that kit kinase inhibitors may fulfill that role someday.

PMID- 10909047
TI  - A proposed classification of mastocytosis incorporating molecular genetics.
AB  - As an understanding of the molecular genetic causes of different forms of
      mastocytosis is developed, the therapy of choice may depend on the specific
      genetic abnormalities expressed by a patient's neoplastic mast cells. The authors
      propose a new classification system for mastocytosis that incorporates both
      molecular-genetic and clinical data. This system provides a theoretic framework
      for mast cell researchers and helps practicing physicians in estimating prognosis
      and determining therapeutic options for individual patients.

PMID- 10909048
TI  - Physiological modeling with virtual cell framework.
AB  - This article describes a computational framework for cell biological modeling and
      simulation that is based on the mapping of experimental biochemical and
      electrophysiological data onto experimental images. The framework is designed to
      enable the construction of complex general models that encompass the general
      class of problems coupling reaction and diffusion.

PMID- 10909049
TI  - Kinetic analysis of dynamics of muscle function.

PMID- 10909050
TI  - Molecular parameters from sedimentation velocity experiments: whole boundary
      fitting using approximate and numerical solutions of Lamm equation.

PMID- 10909051
TI  - Sedimentation velocity analysis of macromolecular assemblies.

PMID- 10909052
TI  - Analysis of weight average sedimentation velocity data.

PMID- 10909053
TI  - Sedimentation equilibrium analysis of mixed associations using numerical
      constraints to impose mass or signal conservation.

PMID- 10909054
TI  - Optimal data analysis using transmitted light intensities in analytical
      ultracentrifuge.

PMID- 10909055
TI  - Ultracentrifugal analysis of molecular mass of glycoproteins of unknown or ill
      defined carbohydrate composition.

PMID- 10909056
TI  - Irregularity and asynchrony in biologic network signals.
AB  - The principal focus of this chapter has been the description of both ApEn, a
      quantification of serial irregularity, and of cross-ApEn, a thematically similar
      measure of two-variable asynchrony (conditional irregularity). Several properties
      of ApEn facilitate its utility for biological time series analysis: (1) ApEn is
      nearly unaffected by noise of magnitude below a de facto specified filter level;
      (2) ApEn is robust to outliers; (3) ApEn can be applied to time series of 50 or
      more points, with good reproducibility; (4) ApEn is finite for stochastic, noisy
      deterministic, and composite (mixed) processes, these last of which are likely
      models for complicated biological systems; (5) increasing ApEn corresponds to
      intuitively increasing process complexity in the settings of (4); and (6) changes
      in ApEn have been shown mathematically to correspond to mechanistic inferences
      concerning subsystem autonomy, feedback, and coupling, in diverse model settings.
      The applicability to medium-sized data sets and general stochastic processes is
      in marked contrast to capabilities of "chaos" algorithms such as the correlation
      dimension, which are properly applied to low-dimensional iterated deterministic
      dynamical systems. The potential uses of ApEn to provide new insights in
      biological settings are thus myriad, from a complementary perspective to that
      given by classical statistical methods. ApEn is typically calculated by a
      computer program, with a FORTRAN listing for a "basic" code referenced above. It
      is imperative to view ApEn as a family of statistics, each of which is a relative
      measure of process regularity. For proper implementation, the two input
      parameters m (window length) and r (tolerance width, de facto filter) must remain
      fixed in all calculations, as must N, the data length, to ensure meaningful
      comparisons. Guidelines for m and r selection are indicated above. We have found
      normalized regularity to be especially useful, as in the growth hormone studies
      discussed above; "r" is chosen as a fixed percentage (often 20%) of the subject's
      SD. This version of ApEn has the property that it is decorrelated from process SD
      -it remains unchanged under uniform process magnification, reduction, and
      translation (shift by a constant). Cross-ApEn is generally applied to compare
      sequences from two distinct yet interwined variables in a network. Thus we can
      directly assess network, and not just nodal, evolution, under different settings-
      e.g., to directly evaluate uncoupling and/or changes in feedback and control.
      Hence, cross-ApEn facilitates analyses of output from myriad complicated
      networks, avoiding the requirement to fully model the underlying system. This is
      especially important, since accurate modeling of (biological) networks is often
      nearly impossible. Algorithmically and insofar as implementation and
      reproducibility properties are concerned, cross-ApEn is thematically similar to
      ApEn. Furthermore, cross-ApEn is shown to be complementary to the two most
      prominent statistical means of assessing multivariate series, correlation and
      power spectral methodologies. In particular, we highlight, both theoretically and
      by case study examples, the many physiological feedback and/or control systems
      and models for which cross-ApEn can detect significant changes in bivariate
      asynchrony, yet for which cross-correlation and cross-spectral methods fail to
      clearly highlight markedly changing features of the data sets under
      consideration. Finally, we introduce spatial ApEn, which appears to have
      considerable potential, both theoretically and empirically, in evaluating
      multidimensional lattice structures, to discern and quantify the extent of
      changing patterns, and for the emergence and dissolution of traveling waves,
      throughout multiple contexts within biology and chemistry.

PMID- 10909058
TI  - Distinguishing models of growth with approximate entropy.

PMID- 10909057
TI  - Distribution methods and analysis of nonlinear longitudinal data.

PMID- 10909059
TI  - Approximate entropy as indication of goodness-of-fit.

PMID- 10909060
TI  - Kinetic models and data analysis methods for fluorescence anisotropy decay.

PMID- 10909061
TI  - Analysis of nonequilibrium facets of pulsatile sex-steroid secretion in presence
      of plasma-binding proteins.

PMID- 10909062
TI  - Monte Carlo simulations of lateral membrane organization.

PMID- 10909063
TI  - Hydrodynamic bead modeling of biological macromolecules.

PMID- 10909064
TI  - Bayesian hierarchical models.

PMID- 10909065
TI  - Monte Carlo applications to thermal and chemical denaturation experiments of
      nucleic acids and proteins.

PMID- 10909066
TI  - Analysis of drug-DNA binding data.

PMID- 10909067
TI  - Neural network techniques for informatics of cancer drug discovery.

PMID- 10909068
TI  - Dynamic network model of glucose counterregulation in subjects with insulin
      requiring diabetes.

PMID- 10909069
TI  - Association of self-monitoring blood glucose profiles with glycosylated
      hemoglobin in patients with insulin-dependent diabetes.

PMID- 10909070
TI  - Outliers and robust parameter estimation.

PMID- 10909071
TI  - Parameter correlations while curve fitting.

PMID- 10909072
TI  - Identifying and counting protein modifications triggered by nitrosative stress.

PMID- 10909073
TI  - Determination of carbonyl groups in oxidized proteins.

PMID- 10909074
TI  - Quantitation of 4-hydroxynonenal protein adducts.

PMID- 10909075
TI  - Detection of oxidative stress in lymphocytes using dichlorodihydrofluorescein
      diacetate.

PMID- 10909076
TI  - The measurement of protein degradation in response to oxidative stress.

PMID- 10909077
TI  - Analysis of the role of the AMP-activated protein kinase in the response to
      cellular stress.

PMID- 10909078
TI  - Detection and activation of stress-responsive tyrosine kinases.

PMID- 10909079
TI  - Detection of DNA-dependent protein kinase in extracts from human and rodent
      cells.

PMID- 10909080
TI  - Expression and assay of recombinant ATM.

PMID- 10909081
TI  - Detection and purification of a multiprotein kinase complex from mammalian cells.
      IKK signalsome.

PMID- 10909082
TI  - Methods to assay stress-activated protein kinases.

PMID- 10909083
TI  - Monitoring the activation of stress-activated protein kinases using GAL4 fusion
      transactivators.

PMID- 10909084
TI  - Use of kinase inhibitors to dissect signaling pathways.

PMID- 10909085
TI  - The development and use of phospho-specific antibodies to study protein
      phosphorylation.

PMID- 10909086
TI  - Peptide assay of protein kinases and use of variant peptides to determine
      recognition motifs.

PMID- 10909087
TI  - Assaying NF-kappa B and AP-1 DNA-binding and transcriptional activity.

PMID- 10909088
TI  - Analysis of the mammalian heat-shock response. Inducible gene expression and heat
      shock factor activity.

PMID- 10909089
TI  - Approaches to define the involvement of reactive oxygen species and iron in
      ultraviolet-A inducible gene expression.

PMID- 10909090
TI  - The human immunodeficiency virus LTR-promoter region as a reporter of stress
      induced gene expression.

PMID- 10909091
TI  - SAGE. The serial analysis of gene expression.

PMID- 10909092
TI  - Analysis of differential gene expression using the SABRE enrichment protocol.

PMID- 10909093
TI  - UVB-regulated gene expression in human keratinocytes. Analysis by differential
      display.

PMID- 10909094
TI  - Heme oxygenase activity. Current methods and applications.

PMID- 10909095
TI  - Analysis of molecular chaperone activities using in vitro and in vivo approaches.

PMID- 10909096
TI  - Analysis of chaperone properties of small Hsp's.

PMID- 10909097
TI  - Analysis of small Hsp phosphorylation.

PMID- 10909098
TI  - Analysis of multisite phosphorylation of the p53 tumor-suppressor protein by
      tryptic phosphopeptide mapping.

PMID- 10909099
TI  - Development of physiological models to study stress protein responses.

PMID- 10909100
TI  - 25 years of Population Trends.
AB  - This article monitors some of the more significant demographic changes over the
      last twenty-five years, depicted in various issues of Population Trends. It is,
      of necessity, selective in coverage in terms of quotes, figures and topics. Other
      articles in this issue go into more depth on specific topics, such as families,
      ethnic minority groups, marriage and divorce, health inequalities and fertility
      and family planning. Consequently, there is some overlap and the articles could
      usefully be cross-referenced. Some coverage is also given to the development of
      sources, international events and selected partnerships outside the Office.
      Relevant legislation enacted over the period is also mentioned.

PMID- 10909101
TI  - Inequalities in health--development and change.
AB  - This article traces the changes that have taken place in the analysis and
      interpretation of health inequalities over the last 25 years. It sets these in
      their historic context, indicates how the debate on their validity and social
      context has shifted over the period and assesses the current evidence on the
      extent and importance of social variations.

PMID- 10909102
TI  - Demographic issues in 1975 and 2000.
AB  - This article explores the demographic subjects which were topical 25 years ago
      and compares them with those of current interest, as reflected not only by the
      articles published in the early, and most recent issues of Population Trends, but
      also by papers of the period in other demographic journals.

PMID- 10909103
TI  - Trends in fertility and contraception in the last quarter of the 20th century.
AB  - The late 1960s and early 1970s saw major changes in access to birth control. This
      article reviews trends in fertility and contraception between 1976 when the
      Family Formation Survey was undertaken and 1998, the latest year for which data
      are available. There has been an increase in mean age at childbirth over the
      period. Some of this increase is possibly a result of childbearing in second and
      subsequent relationships when the women will be older on average. This also has
      had an impact on their patterns of contraception use. Teenage pregnancy is high
      on the Government's agenda. Teenage pregnancy continues at constant levels. As
      the estimated age of first intercourse decreases, there is a continued need for
      sufficient, accessible and appropriate family planning services.

PMID- 10909104
TI  - Developments in census taking in the last 25 years.
AB  - This article looks back at censuses of population conducted since 1971. It
      identifies some of the most important changes with respect to questions asked,
      methods of collecting the census and the production of outputs. In particular it
      discusses the introduction of the ONS Longitudinal Study following the 1971
      Census and the Samples of Anonymised Records following the 1991 Census. This
      article outlines some of the changes being introduced for the 2001 Census,
      including methods of dealing with under-enumeration and improved access to
      outputs.

PMID- 10909105
TI  - Understanding managed behavioral health care.
AB  - Managed care can be understood from an historical perspective as a reaction to
      perceived abuses by providers or an extension of earlier efforts to manage care
      in the public sector. It can be viewed as a young and emerging force--a fourth
      party to the health care transaction--that is rapidly progressing through a
      series of generations that redefine the approach to organizing and delivering
      services. And finally, because managed care emerges with so many faces, consumers
      and providers can perhaps best understand its implementation in a specific state
      or community by examining the multiple dimensions, such as those outlined herein,
      on which these initiatives vary. Until the forms and functions are more uniform,
      no simple definition of managed care will exist.

PMID- 10909106
TI  - The economics of managed care in behavioral health. Basic concepts and
      incentives.
AB  - Psychiatrists and other behavioral health clinicians must accept managed care
      philosophy because it is not going to disappear. A keen understanding of the
      specific issues that are pertinent to the managed care contracts that are signed
      is important if the clinician is to serve as an effective advocate for his or her
      patients on a case by case basis. Managed care in behavioral health services is
      now preparing to enter a new phase in development in which there will be reduced
      competition amongst the BHMCOs because the number of managed care organizations
      are decreasing with mergers and acquisitions. These adjustments in the market
      will leave the clinician and the provider organization potentially less able to
      make changes in their own delivery systems unless the discussions and strategies
      for change are structured in such a way that the incentives for all involved
      parties are aligned. Stakeholders in the process of managing care for behavioral
      health will need to come together to educate all parties about the value of
      necessary behavioral health treatment at the point of need. Appropriate access to
      all necessary behavioral health services could create additional short-term
      costs, but with reasonable management of the services, these costs could be kept
      in line.

PMID- 10909107
TI  - Ethics in managed care.
AB  - The current era of managed costs and care create ethical dilemmas based on
      economic constraints and incorporation of principles of distributive justice.
      Traditional ethical concerns related to confidentiality, conflicts of interest,
      double agentry, and honesty are complicated by interference in the doctor-patient
      relationship caused by intrusive utilization management. National health reform
      must take these issues seriously to ensure that the "cure" promised by such
      reform efforts is not worse than the disease. The challenge for psychiatrists is
      to adapt to these constraints without losing site of traditional medical ethical
      positions. Once the ethics become diseased, no cure may exist at all.

PMID- 10909108
TI  - Understanding the intersection between quality improvement, managed behavioral
      health accreditation, and the private practitioner.
AB  - The many parties, which now possess a role in behavioral health care services,
      are each concerned about the quality of these services. The concept of
      accreditation of MBHOs differs little from the board certification and licensure
      mechanisms used to ensure a minimal standard of care among practitioners. In the
      same way that behavioral health patients use licensure to seek competent
      providers, payers use accreditation as a way to ensure that MBHOs, given the task
      of cost control, are also active in ensuring that cost containment does not
      translate into decreased quality of care. Accreditation has established standards
      that fundamentally require MBHOs to implement QI programs directed at assessing
      and implementing efforts to improve care on a systemic level. NCQA accreditation
      of MBHOs reflects an effort to both regulate a novel industry as well as
      establish standards that reflect an ideal of health care. Currently, relatively
      few MBHOs receive full accreditation. This suggests that NCQA maintains its
      ideals but also that many MBHOs do not have the quality improvement programs that
      adequately demonstrate an interest in assessing and improving upon continuity and
      population-based quality care. As a fledgling industry, MBHOs are subject to
      unique market demands and trial and error. These forces have alienated many
      practitioners who provide services to MBHO members; however, practitioners must
      be able to tease out those aspects of managed care that facilitate quality care
      for their patients. Fundamental to this is the need for practitioners to
      understand and contribute meaningfully to QI initiatives directed at meeting NCQA
      standards. Despite their impositions, the new demands they place on
      practitioners, and the conflicted relationship in which they take place, QI
      efforts reflect an effort on the part of accrediting organizations and MBHOs to
      define, through empirical assessment and improvement efforts, quality care at a
      systemic level. Such care directly relates to effective behavioral health care by
      ensuring that a population of members receives care over a continuum of time and
      setting. Accreditation standards ultimately translate into quality of care and
      service, which patients and practitioners as well as the other stakeholders in
      the health care marketplace, agree is important.

PMID- 10909109
TI  - Monitoring change in behavioral health care. The role of the Center for Mental
      Health Services.
AB  - One of the strategic goals of the Substance Abuse and Mental Health Services
      Administration (SAMHSA) is to improve managed care outcomes. This report from the
      Office of Managed Care, Center for Mental Health Services, summarizes the results
      of six SAMHSA projects. The studies discussed were selected because they have
      yielded substantive findings. One nationwide evaluation showed increasing
      complexity in contracts between state Medicaid agencies and managed care
      organizations, as states move toward greater use of managed mental health and
      substance abuse program arrangements and greater inclusion of persons with
      disabilities. A report from SAMHSA's Managed Care Tracking System indicates that,
      contrary to predictions, most public-sector mental health and substance abuse
      programs are managed by public-sector agencies or public or private partnerships
      rather than by private managed care organizations. Also, an analysis of pre
      managed care Medicaid data on mental health and substance abuse services in 10
      states is serving as a baseline to assess the effects of managed care on Medicaid
      mental health and substance abuse program use and costs.

PMID- 10909110
TI  - Medical necessity and psychiatric managed care.
AB  - The concept of medical necessity is a provision of commercial insurance contracts
      and federal government Medicaid requirements that limits the payment to only
      those services that are essential for treating a person's sickness, injury, or
      condition. The concept of medical necessity is one tool used by third-party
      payers to contain their financial risk in a seemingly nonarbitrary manner. Also,
      the definitions of medical necessity used by commercial insurers or by the
      federal government reflect their product's or program's philosophies. Expanding
      commercial insurance or Medicaid psychiatric coverage would require changing
      those philosophies. As long as society is faced with a greater demand for health
      related service than resources to meet them, such systems of rationing will be
      used. Even with full parity for psychiatric benefits, mechanisms will be used by
      payers to limit or control demand, thereby controlling financial risk. The short
      term challenge for psychiatric advocates is to secure the most acceptable
      definitions of medical necessity from third-party payers. The long-term challenge
      for MH/SA advocates and for all health care advocates, is to develop a system
      that pays for the greatest number of quality services for the greatest number of
      people in need, in an affordable manner, regardless of diagnosis.

PMID- 10909111
TI  - Changes in inpatient psychiatric utilization and quality of care performance
      measures in a capitated HMO population, 1989-1999.
AB  - Managed behavioral health care approaches have significantly reduced inpatient
      utilization and related cost of care, but the relationship between decreased
      utilization and cost of care to changes in quality of care performance over time
      remains in question. The trends in utilization and quality of care performance
      measures over the course of 10 years of the Tufts Health Plan Designated Facility
      Program, a model health maintenance organization capitated program for inpatient
      behavioral health care, are presented. The results indicate that substantial
      decreases in inpatient utilization were sustained while quality of care measures
      improved over time. The data support the Tufts Health Plan Designated Facility
      Program as a successful means of balancing cost containment with quality of care.

PMID- 10909112
TI  - Alternative treatment programs. The psychiatric continuum of care.
AB  - Many of the components of the continuum originated in legislation that created
      the community mental health centers. The continuum grew in breadth and depth with
      the arrival of managed care because it offered less expensive ways to satisfy
      patient needs. Over the past decade, days spent in hospital have decreased from
      more than 100 per thousand individuals in some health plans to less than 20 for
      the same populations. Greatly reduced rates of admission and shortened lengths of
      stay made this decrease possible. But simply being quicker and cheaper is not
      good enough. To fulfill their promise, the components of the continuum and the
      larger delivery systems must provide care that is of superior quality and
      outcome. An important next step in the evolution of the continuum will be to
      generate the data that will make it possible to evaluate program performance,
      compare treatment alternatives, and usher in an era of evidence-based mental
      health care.

PMID- 10909113
TI  - Clinical status. Charting for outcomes in behavioral health.
AB  - This article summarizes the criteria that clinical outcome data must meet to be
      useful in the quest for empirical effectiveness data about mental health
      services. Although demand is high for such data, its potential usefulness is just
      beginning to be tapped. The mental health field presents unique challenges for
      implementing outcome tracking systems, for analyzing and reporting results, and
      for using results to improve the processes of care. Measuring outcomes will not
      automatically improve care or ensure quality. It may, however, provide
      information that will be useful in guiding efforts to improve the quality of
      mental health services.

PMID- 10909114
TI  - Mapping the road to quality collaborative patient care in a behavioral health
      community treatment center. Avoiding the detours of managed care.
AB  - At this writing, the system and tools described have improved the author's
      organization's ability to meet managed care requirements better and support a
      collaborative care and case management model. Refer to the boxed information for
      the key functions and outcomes of the system. The Behavioral Health Multiaxial
      Protocol CareMapping System offers one approach to addressing the dilemma of
      health environmental change, managed care requirements, and financial constraints
      that have the potential to endanger the quality of clinical practice and to have
      a negative effect on patient and family outcomes. The tools illustrated in this
      article are in a constant cycle of revision and improvement and requires adequate
      clerical support to accommodate revision and tool improvement. Many more
      improvement initiatives are needed to improve the patient care process and
      organizational performance continuously. Because quality is a journey, the author
      hopes that her institution is on the right road and carries the correct map.

PMID- 10909115
TI  - The adaptive practice of psychotherapy in the managed care era.
AB  - Managed care is the current state of health care delivery. How to respond to
      managed care's provider expectations is the key issue for all mental health care
      professionals. The adaptive response, based on managed care's definition of value
      and regardless of theoretic orientation, must be clear and definitive in terms of
      what the provider will do; why the provider will do it; how the provider will
      specifically achieve patient relief; and how the provider, patient, and managed
      care representative will know when that change has been achieved. In the managed
      care era, clinicians must satisfy patients, managed care representatives, and
      themselves by producing a valid and effective treatment product for all parties
      involved in the interplay of mental health care delivery.

PMID- 10909116
TI  - Developing outpatient mental health services for managed care.
AB  - One of the characteristics of the best outpatient treaters is their capacity to
      manage their own anxieties so as not to interfere with their patients' progress.
      This does not mean "sitting on," shutting out, or otherwise ignoring those
      signals to prevent their intruding into the therapeutic space. On the contrary,
      this requires that a clinician be acutely aware of his or her internal dialogue
      and be able to listen to use it to facilitate the treatment. This has meant
      simultaneously listening to oneself while paying complete attention to one's
      patient. This paradox is part of the nature of this work and remains one of its
      important features. Today, those who choose to treat psychiatric patients in this
      setting are presented with many more such paradoxes, including the necessity of
      being aware of (1) populations needing to be served while providing the best care
      for individual patients; (2) limited resources; and (3) balancing ethical,
      fiscal, legal, and clinical concerns. This article demonstrates that the
      successful development of outpatient services in a managed care environment
      requires attention to these same tensions on a larger scale. It also shows that
      understanding the evolution of managed care and the myriad competing interests
      involved are necessary to be able to care successfully for psychiatric patients.

PMID- 10909117
TI  - Private psychiatric practice in an era of managed care.
AB  - Managed care is a given for private practice right now. It is important to
      develop a practice you can be proud of and be comfortable to work in by
      practicing ethically, with high standards for quality. Be persistent in expecting
      the same from the managed care companies, your colleagues, and your patients.
      Solid clinical and business principles are the backbone of private practice.

PMID- 10909118
TI  - The collaboration between psychiatry and primary care in managed care.
AB  - Primary care physicians have an important historical role in the delivery of
      mental health care despite the evolution of psychiatry as a specialty.
      Collaboration between primary care physicians and psychiatrists has been limited
      by problems of access to psychiatric care or consultation. Although managed care,
      in some forms, has been successful in addressing this issue, it has largely
      served as a new barrier to effective collaboration and to meeting the mental
      health care needs of patients.

PMID- 10909119
TI  - Geriatric psychiatry and managed care.
AB  - A wide gap exists in the American health care system between what we know good
      geriatric mental health care services should look like and the types of services
      generally available. Cost effective treatment requires a continuum of care in
      which geriatric psychiatry and primary care geriatric services are integrated in
      an aggressively case managed model. MCOs have the infrastructure and tools at
      their disposal to make this work, but they must incorporate into their programs
      and approaches expert knowledge of the unique clinical problems of the frail
      elderly.

PMID- 10909120
TI  - Training psychiatric residents in managed care.
AB  - The controversy about managed care in general is reflected in the challenges of
      training psychiatric residents in managed care. Some consensus is emerging that
      all programs should provide some amount of such education. Moreover, some
      principles and strategies seem to exist that any program can adapt and use,
      including neutral attitude, connecting managed care to related educational
      endeavors, emphasizing cost-effectiveness as a primary value, providing a basic
      seminar series, and approaching a core patient group using managed care
      management.

PMID- 10909121
TI  - Does intra-uterine growth discordance predict differential risk for adult
      psychiatric disorder in a population-based sample of monozygotic twins?
AB  - The study of discordant monozygotic twins may identify important developmental
      risk factors for adult psychiatric disorder. Differential experience in utero is
      one candidate environmental risk factor that may distinguish monozygotic twins.
      In this report, we examine whether intra-pair differences in birth weight
      predicts discordance for adult psychiatric disorders in 527 female monozygotic
      twin pairs from a population-based twin registry. Twins were personally
      interviewed about their lifetime history of DSM-III-R alcoholism, anorexia
      nervosa, bulimia nervosa, generalized anxiety disorder, major depression, panic
      disorder, social phobia and simple phobia. Birth weight was estimated from birth
      certificates, or from retrospective maternal, paternal and self-reports.
      Conditional logistic regression is used to characterize the association between
      intra-pair differences in birth weight and discordance for psychiatric disorder
      in monozygotic twins. The twin with the heavier birth weight in discordant pairs
      is (insignificantly) more likely to have a history of alcoholism or bulimia. The
      twin with the lighter birth weight in discordant pairs is (insignificantly) more
      likely to have a history of major depression, simple phobia, panic disorder,
      anorexia nervosa, social phobia or generalized anxiety disorder. For all
      psychiatric disorders examined, the lighter (or heavier) co-twin at birth is not
      systematically the affected twin within discordant pairs.

PMID- 10909122
TI  - Association between cytochrome P4502D6 (CYP2D6) genotype, antipsychotic exposure,
      and abnormal involuntary movement scale (AIMS) score.
AB  - Antipsychotic metabolism cosegregates with the polymorphic cytochrome P4502D6
      (CYP2D6) hepatic enzyme. Approximately 5-10% of Caucasians show impaired
      metabolism associated with nonfunctional alleles. Genotyping determines the
      number of functional alleles, which is phenotypically not possible. The aim of
      this study was to investigate associations between CYP2D6 genotype, antipsychotic
      exposure, and abnormal involuntary movement scale (AIMS) score. Schizophrenic
      patients (DSM-IV) were genotyped for CYP2D6*1, *3, and *4 alleles by nested
      polymerase chain reaction. A complete history, including psychiatric symptoms,
      medications and AIMS score was obtained. Antipsychotic exposure was recorded in
      dose years [(chlorpromazine equivalents x years)/100]. A linear regression model
      used AIMS scores as the dependent variable. Genotype, gender, antipsychotic
      exposure, and interactions were independent variables. The results of the 31
      patients studied showed: 20 were homozygous for the *1 allele (*1/*1) and 11 were
      heterozygous for the *1 allele (i.e. *1/*3 or *4). Age, sex, age of onset,
      treatment duration, antipsychotic exposure, and AIMS scores did not differ
      between groups. The interaction between dose years and genotype was significant
      (P < 0.0055), demonstrating that for (*1/*1) patients, the magnitude of
      antipsychotic exposure had a greater effect on AIMS score (slope = 0.044)
      compared with (*1/*3 or *4) patients (slope = 0.001). These results suggest
      patients with a *3 or *4 allele may have a higher risk for developing
      antipsychotic induced abnormal movements.

PMID- 10909123
TI  - Tryptophan hydroxylase polymorphisms in suicide victims.
AB  - Both environmental and genetic factors appear to contribute to the risk for
      suicide. The serotonergic system has been implicated in depression, impulsivity
      and suicidality. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the
      synthesis of serotonin. Suicide has been associated with polymorphisms in intron
      7 of the TPH gene. These alleles were studied in samples from 47 deceased
      Caucasian males as part of the Utah Youth Suicide Study. A 918 base pair fragment
      spanning the region of interest was amplified. The A218C polymorphism was
      visualized by restriction fragment length polymorphism (RFLP) and the A779C was
      sequenced. Neither A218C nor A779C appeared to be associated with suicide in this
      population. These results did not change when the sample was stratified by age
      (10-21 years, 22-31 years) or when violent suicides were selected. The complexity
      of the phenotype of suicide may reflect multiple biological and social etiologic
      factors, and poses a worthy challenge for genetic studies.

PMID- 10909124
TI  - Search for association between suicide attempt and serotonergic polymorphisms.
AB  - Serotonergic neurotransmission has been implicated in suicidal behavior.
      Polymorphisms in the genes coding for tryptophan hydroxylase, serotonin receptor
      2A and serotonin transporter were investigated in a sample of suicide attempters
      (n = 165) and healthy control subjects (n = 99). No significant differences were
      found for any of the investigated polymorphisms. Neither did any significant
      differences emerge in comparison with control subjects when the suicide
      attempters were grouped into different diagnostic categories: unipolar disorder
      (n = 45), adjustment disorder (n = 37), substance use disorder (n = 37) and
      personality disorder, cluster B (n = 36). The results suggest that alleles
      defined by the investigated polymorphisms do not represent a major determinant in
      suicide attempt. However, a highly significant (P = 0.001; odds ratio, 1.47; 99%
      confidence interval, 1.42-1.53) allelic association between tryptophan
      hydroxylase and suicide attempt is indicated after pooling our data with
      literature data. In light of previous data, a possible association between the
      tryptophan hydroxylase polymorphism and a phenotype that may become differently
      stratified within differently selected samples of suicide attempters is
      discussed.

PMID- 10909125
TI  - Mitochondrial DNA variants in schizophrenia: association studies.
AB  - The frequency of three selected mitochondrial DNA variations was compared between
      cases with schizophrenia and two groups of unrelated controls: screened adults
      and neonates. The comparisons were conducted separately among Caucasians and
      African-Americans. No significant differences were detected, suggesting that the
      variants may not be associated with schizophrenia. Limitations of the study are
      discussed.

PMID- 10909126
TI  - Repeat sizes at CAG/CTG loci CTG18.1, ERDA1 and TGC13-7a in schizophrenia.
AB  - A number of studies using the repeat expansion detection (RED) technique have
      suggested an association between unknown large CAG/CTG repeats and schizophrenia.
      The polymorphic CAG/CTG repeat loci CTG18.1 and ERDA1 have been reported to
      account for a high proportion (approximately 90%) of the large repeats detected
      by RED and may therefore be responsible for the cited association. The recently
      described locus TGC13-7a contains a highly polymorphic CTA/TAG and CAG/CTG
      composite repeat, and is thus another authentic candidate. In the present
      investigation, each locus was analysed for association with schizophrenia in a
      sample of 206 patients and 219 group-matched controls. No evidence for
      association of CTG18.1, ERDA1 and/or TGC13-7a with schizophrenia was found. The
      combined data accounted for only 54% of the CAG/CTG arrays of > 40 repeats found
      in our previous RED analysis.

PMID- 10909127
TI  - Association between the adrenergic alpha 2A receptor gene (ADRA2A) and measures
      of irritability, hostility, impulsivity and memory in normal subjects.
AB  - The noradrenergic system has been implicated in arousal, vigilance, irritability
      hostility, and memory. This suggests the hypothesis that genetic variants at
      noradrenergic receptors may be risk factors of these behaviors. To test this
      hypothesis, the potential association between measures of these traits and
      genetic variation at the adrenergic2A receptor gene (ADRA2A), using a common
      single nucleotide polymorphism (SNP) polymorphism of the promoter region, were
      examined in two independent sets of subjects: university students (student
      group), and parents of twins in the Minnesota Twin Study (twin group). In the
      student group, there was a significant linear association by genotype (11 > 12 >
      22) for the total Brown ADD score (BADD), and BADD subscores of memory and
      irritability, and with the total Buss-Durkee Hostility Inventory (BDHI) score and
      BDHI subscores of indirect hostility, irritability, negativity, and verbal
      aggression. A multiple analysis of variance (MANOVA) of all the BADD and BDHI
      subscores was significant at P < or = 0.009. For the twin group, the same
      genotype associations were significant for the Multidimensional Personality
      Questionnaire (MPQ) impulsivity scores but not for the MPQ aggression or harm
      avoidance scores. The ADRA2A gene accounted for 1.8-8.3% of the variance of these
      scores.

PMID- 10909128
TI  - Possible involvement of the dopamine D3 receptor locus in subtypes of bipolar
      affective disorder.
AB  - The dopamine D3 receptor gene is of potential interest in the physiopathology of
      affective disorder because of its expression pattern in brain structures
      controlling various aspects of behaviour, cognition and emotions. Moreover, it
      encodes for a receptor protein that is a target for psychotropic drugs, which
      turn out to be efficient in the treatment of this disorder. Two polymorphisms
      have been described at this locus (the Bal I and the Msp I Restriction Fragment
      Length Polymorphisms) that are useful in genetic studies. We therefore researched
      these polymorphisms in 60 patients suffering from bipolar affective disorder who
      were compared with 60 healthy volunteers. No statistical difference was observed
      between the whole patient sample versus the controls. However, one subgroup
      [homozygous for the (2-2) Bal I polymorphism] exhibits a characteristic clinical
      pattern consisting of: manic monopolar form of bipolar disorder, low age of onset
      and initiation by an acute delusional episode. A gender distribution difference
      for the Bal I polymorphism (chi 2 = 6.61, degrees of freedom = 1, P = 0.01) was
      then noted, the bipolar females being preferentially heterozygous, and the males
      homozygous. These results could involve the dopamine D3 receptor locus as a minor
      effect gene in the manic depression condition.

PMID- 10909129
TI  - Association analysis of the proneurotensin gene and bipolar disorder.
AB  - Neurotensin (NT) localizes within dopaminergic neurones in the mesocortical,
      mesolimbic and nigrostriatal systems, and it is now clear that NT can selectively
      modulate dopaminergic neurotransmission. It has therefore been proposed that
      altered NT function might contribute to the pathogenesis of neuropsychiatric
      disorders in which disordered dopaminergic neurotransmission is suspected. We
      have previously screened the gene encoding NT in a sample of schizophrenic and
      bipolar subjects, and identified three sequence variants. These have now been
      tested for association with bipolar disorder using a case-control sample of
      unrelated bipolar subjects and matched controls. No evidence for association was
      found, and our data therefore suggest that sequence variation in this gene does
      not make an important contribution to susceptibility to bipolar disorder.

PMID- 10909130
TI  - Bipolar disorder and chromosome 18p11: uncertainties redux.

PMID- 10909131
TI  - The power law repealed: the case for an exponential law of practice.
AB  - The power function is treated as the law relating response time to practice
      trials. However, the evidence for a power law is flawed, because it is based on
      averaged data. We report a survey that assessed the form of the practice function
      for individual learners and learning conditions in paradigms that have shaped
      theories of skill acquisition. We fit power and exponential functions to 40 sets
      of data representing 7,910 learning series from 475 subjects in 24 experiments.
      The exponential function fit better than the power function in all the unaveraged
      data sets. Averaging produced a bias in favor of the power function. A new
      practice function based on the exponential, the APEX function, fit better than a
      power function with an extra, preexperimental practice parameter. Clearly, the
      best candidate for the law of practice is the exponential or APEX function, not
      the generally accepted power function. The theoretical implications are
      discussed.

PMID- 10909132
TI  - A comparison of two response time models applied to perceptual matching.
AB  - Two models, a Poisson race model and a diffusion model, are fit to data from a
      perceptual matching task. In each model, information about the similarity or the
      difference between two stimuli accumulates toward thresholds for either response.
      Stimulus variables are assumed to influence the rate at which information
      accumulates, and response variables are assumed to influence the level of the
      response thresholds. Three experiments were conducted to assess the performance
      of each model. In Experiment 1, observers performed under different response
      deadlines; in Experiment 2, response bias was manipulated by changing the
      relative frequency of same and different stimuli. In Experiment 3, stimulus pairs
      were presented at three eccentricities: foveal, parafoveal, and peripheral. We
      examined whether the race and diffusion models could fit the response time and
      accuracy data through changes only in response parameters (for Experiments 1 and
      2) or stimulus parameters (for Experiment 3). Comparisons between the two models
      suggest that the race model, which has not been studied extensively, can account
      for perceptual matching data at least as well as the diffusion model.
      Furthermore, without the constraints on the parameters provided by the
      experimental conditions, the diffusion and the race models are indistinguishable.
      This finding emphasizes the importance of fitting models across several
      conditions and imposing logical psychological constraints on the parameters of
      models.

PMID- 10909133
TI  - Metaphor comprehension: a computational theory.
AB  - Metaphor comprehension involves an interaction between the meaning of the topic
      and the vehicle terms of the metaphor. Meaning is represented by vectors in a
      high-dimensional semantic space. Predication modifies the topic vector by merging
      it with selected features of the vehicle vector. The resulting metaphor vector
      can be evaluated by comparing it with known landmarks in the semantic space.
      Thus, metaphorical prediction is treated in the present model in exactly the same
      way as literal predication. Some experimental results concerning metaphor
      comprehension are simulated within this framework, such as the nonreversibility
      of metaphors, priming of metaphors with literal statements, and priming of
      literal statements with metaphors.

PMID- 10909134
TI  - Comparative cognition in the 1930s.
AB  - According to the received view of the history of psychology, behaviorism so
      dominated psychology prior to the 1960s that there was little research in animal
      cognition. A review of the research on animal cognition during the 1930s reveals
      a rich literature dealing with such topics as insight, reasoning, tool use, delay
      problems, oddity learning, abstraction, spatial cognition, and problem solving,
      among others. Material on "higher processes" or a related topic was prominent in
      the textbooks of the period. Tracing academic lineages reveals such teachers as
      Harvey Carr, Robert M. Yerkes, and Edward C. Tolman as sources of this interest.
      The alleged hegemony of strict behavioristic psychology, interpreted as excluding
      research on animal cognition, requires revision. Some possible reasons for this
      neglect are suggested.

PMID- 10909135
TI  - Pigeon reaction time, Hick's law, and intelligence.
AB  - Pigeons' choice reaction times (RTs) increased as a linear function of log2
      number of potential target stimuli (Experiments 1-3), as would be predicted by
      Hick's law. The values of intercepts and slopes decreased with training
      (Experiments 2 and 3) and with differential reinforcement of short RTs under
      percentile reinforcement contingencies (Experiment 3). RT functions obtained from
      human subjects were also consistent with Hick's law, but slopes for pigeons were
      significantly lower than those for humans (Experiments 4 and 5). These results
      extend the generality of Hick's law to pigeons but are inconsistent with Jensen's
      claim that the parameters of the Hick function are related to intelligence.

PMID- 10909136
TI  - Tracking visual search over space and time.
AB  - Visual perception consists of early preattentive processing and subsequent
      attention-demanding processing. Most researchers implicitly treat preattentive
      processing as a domain-dependent, indivisible stage. We show, however, by
      interrupting preattentive visual processing of color before its completion, that
      it can be dissected both temporally and spatially. The experiment depends on
      changing easy (preattentive) selection into difficult (attention-demanding)
      selection. We show that although the mechanism subserving preattentive selection
      completes processing as early as 200 msec after stimulus onset, partial selection
      information is available well before completion. Furthermore, partial selection
      occurs first at locations near fixation, spreading radially outward as processing
      proceeds.

PMID- 10909137
TI  - Selective attention to the parts of an object.
AB  - Recent empirical results suggest that there is a decrement in dividing attention
      between two objects in a scene compared with focusing attention on a single
      object. However, objects can be made of individual parts. Is there a decrement
      for dividing attention across different parts of a single object? We addressed
      this question in two experiments. In Experiment 1, we demonstrated that attention
      can exhibit part-based selection--that is, the subjects were more accurate in
      reporting two attributes from the same part of an object than they were in
      reporting attributes from different parts of an object. In Experiment 2, we
      demonstrated that part-based attentional decrements occurred simultaneously with
      object-based attentional decrements. The results from Experiment 2 demonstrated
      that part-based attention is evident at the same time as objects are processed as
      coherent whole. Our results imply that there is an attentional mechanism that can
      select either objects or their parts.

PMID- 10909138
TI  - Another wrinkle on the dual-task SRT experiment: it's probably not dual task.
AB  - In the standard serial reaction time (SRT) experiment, subjects are required to
      respond rapidly to a structured sequence of visual targets. Evidence that
      subjects have acquired knowledge of the structure is obtained by modifying the
      structured nature of the sequence and noting whether reaction times increase. In
      the dual-task SRT experiment, a "secondary" tone-counting task is introduced, and
      the extent to which learning of the "primary" target sequence is compromised is
      noted. Here we present data that strongly imply that while the psychologists who
      designed this "dual-task" experiment may have viewed it this way, this may not be
      the best way to characterize it. The suggestion is that this "duality" is
      illusory and that we should probably be treating the tone-counting task as a
      potential source of additional patterns of covariation in a complex,
      multicomponent display and not as a "secondary," attention-diverting factor.

PMID- 10909139
TI  - Phonological priming effects on speech onset latencies and viewing times in
      object naming.
AB  - An earlier experiment (Meyer, Sleiderink, & Levelt, 1998) had shown that speakers
      naming object pairs usually inspected the objects in the required order of
      mention (left object first) and that the viewing time for the left object
      depended on the word frequency of its name. In the present experiment, object
      pairs were presented simultaneously with auditory distractor words that could be
      phonologically related or unrelated to the name of the object to be named first.
      The speech onset latencies and the viewing times for that object were shorter
      after related distractors than after unrelated distractors. Since this
      phonological priming effect, like the word frequency effect, most likely arises
      during word-form retrieval, we conclude that the shift of gaze from the first to
      the second object is initiated after the word form of the first object's name has
      been accessed.

PMID- 10909140
TI  - The interaction of meaning and sound in spoken word recognition.
AB  - Models of spoken word recognition vary in the ways in which they capture the
      relationship between speech input and meaning. Modular accounts prohibit a word's
      meaning from affecting the computation of its form-based representation, whereas
      interactive models allow activation at the semantic level to affect phonological
      processing. We tested these competing hypotheses by manipulating word familiarity
      and imageability, using lexical decision and repetition tasks. Responses to high
      imageability words were significantly faster than those to low-imageability
      words. Repetition latencies were also analyzed as a function of cohort variables,
      revealing a significant imageability effect only for words that were members of
      large cohorts, suggesting that when the mapping from phonology to semantics is
      difficult, semantic information can help the discrimination process. Thus, these
      data support interactive models of spoken word recognition.

PMID- 10909141
TI  - Proactive interference of a sequence of tones in a two-tone pitch comparison
      task.
AB  - Subjects compared pitches of a standard tone and a comparison tone separated by
      1,300-3,000 msec and responded according to whether the comparison tone sounded
      higher or lower in pitch than the standard tone. Three interfering tones at 300
      msec intervals were presented before each pair of tones. Their pitch range
      varied, being either below or above the pitch of the standard tone; in some of
      the trials, their pitches were identical to the pitch of the standard tone (no
      interference). The highest error rate in performance was found when the
      interfering tones and the comparison tone deviated in the same direction in pitch
      from the standard tone. In turn, their deviations in the opposite directions
      resulted in the lowest error rate. This effect was not found to be dependent on
      whether the interfering tones were randomly ordered or monotonically ordered,
      together with the standard tone, into melodically ascending/descending sequences.
      An intermediate error rate in performance was found when the interfering tones
      and the standard tone were identical. The results support earlier hypotheses,
      presented in the context of retroactive interference, by demonstrating proactive
      interference of a tone sequence at the level of representations of individual
      tones.

PMID- 10909142
TI  - Immediate serial recall of words and nonwords: tests of the retrieval-based
      hypothesis.
AB  - In two experiments, the immediate serial recall of lists of words or nonwords was
      investigated under quiet and articulatory suppression conditions. The results
      showed better item recall for words but better order recall for nonwords, as
      measured with proportion of order errors per item recalled. Articulatory
      suppression hindered the recall of item information for both types of lists and
      of order information for words. These results are interpreted in light of a
      retrieval account in which degraded phonological traces must undergo a
      reconstruction process calling on long-term knowledge of the to-be-remembered
      items. The minimal long-term representations for nonwords are thought to be
      responsible for their lower item recall and their better order recall. Under
      suppression, phonological representations are thought to be minimal, producing
      trace interpretation problems responsible for the greater number of item and
      order errors, relative to quiet conditions. The very low performance for nonwords
      under suppression is attributed to the combination of degraded phonological
      information and minimal long-term knowledge.

PMID- 10909143
TI  - Short-term implicit memory: visual, auditory, and cross-modality priming.
AB  - Short-term implicit memory was examined for mixed auditory (A) and visual (V)
      stimuli. In lexical decision, words and nonwords were repeated at lags of 0, 1,
      3, and 6 intervening trials, in four prime-target combinations (VV, VA, AV, AA).
      Same-modality repetition priming showed a lag x lexicality interaction for visual
      stimuli (nonwords decayed faster), but not for auditory stimuli (longer lasting
      smooth decay for both words and nonwords). These modality differences suggest
      that short-term priming has a perceptual locus, with the phonological lexicon
      maintaining stimuli active longer than the orthographic lexicon and treating
      pseudowords as potential words. We interpret these differences in terms of the
      different memory needs of speech recognition and text reading. Weak cross
      modality short-term priming was present for words and nonwords, indicating
      recoding between perceptual forms.

PMID- 10909144
TI  - Direct comparison of auditory implicit memory tests.
AB  - In this experiment, we examined the degree to which four implicit tests and two
      explicit tests, all involving auditory presentation, were sensitive to the
      perceptual characteristics of the stimuli presented during study. Presenting
      stimuli visually decreased priming in all the implicit memory tests, relative to
      auditory presentation. However, changing voice between study and test decreased
      priming only in the implicit memory tests requiring identification of words
      degraded by noise or by low-pass filtering, but not in those tests requiring
      generation from word portions (stems and fragments). Modality effects without
      voice effects were observed in cued recall, but the opposite pattern of results
      (voice effects without modality effects) was obtained in recognition. The primary
      new finding is the demonstration that auditory memory tests, both explicit and
      implicit, differ in their sensitivity to the perceptual information encoded
      during study.

PMID- 10909146
TI  - The psychological side of Hempel's paradox of confirmation.
AB  - People often test hypotheses about two variables (X and Y), each with two levels
      (e.g., X1 and X2). When testing "If X1, then Y1," observing the conjunction of X1
      and Y1 is overwhelmingly perceived as more supportive than observing the
      conjunction of X2 and Y2, although both observations support the hypothesis.
      Normatively, the X2&Y2 observation provides stronger support than the X1&Y1
      observation if the former is rarer. Because participants in laboratory settings
      typically test hypotheses they are unfamiliar with, previous research has not
      examined whether participants are sensitive to the rarity of observations. The
      experiment reported here showed that participants were sensitive to rarity, even
      judging a rare X2&Y2 observation more supportive than a common X1&Y1 observation
      under certain conditions. Furthermore, participants' default strategy of judging
      X1&Y1 observations more informative might be generally adaptive because
      hypotheses usually regard rare events.

PMID- 10909145
TI  - Direct versus indirect tests of memory: directed forgetting meets the generation
      effect.
AB  - Subjects read 20 words and generated 20 others from definitions during a 40-item
      study phase. Production of each word was followed by an instruction to remember
      or to forget that word. In free recall, a direct test of memory, words that had
      been generated were recalled much better than words that had been read. The
      remember-forget instructional manipulation affected read words but not generated
      words. In speeded word reading, an indirect test of memory, all studied words
      showed priming, but read words showed more priming than generated words. Here,
      the effect of remember versus forget instructions appeared only for generated
      words. These dissociations of a direct and an indirect test indicate that two
      powerful encoding manipulations affect separable processes to which these tests
      are differentially sensitive.

PMID- 10909147
TI  - [Is atherosclerosis an infectious disease].

PMID- 10909148
TI  - [Consensus conference].

PMID- 10909149
TI  - [Drug-addicted prisoners: seroprevalence of human immunodeficiency virus and
      hepatitis B and C virus soon after the marketing of buprenorphine].
AB  - PURPOSE: Considering the importance to public health and the frequency with which
      drug addicts are imprisoned, we studied the prevalence of human immunodeficiency
      virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), as well as drug
      addiction of patients admitted to the Elsau prison in Strasbourg (France).
      METHODS: The prospective study included all entering inmates from 1 September to
      31 October 1997 (270 persons) to whom HIV, HBV and HCV blood tests were offered
      as well as a questionnaire on their drug addiction. RESULTS: Thirty-six percent
      of the entering inmates were drug addicts, of whom 1% were HIV positive, 11.2%
      HBV positive and 30% HCV positive, compared to, respectively, 0.6, 9.9 and 6.4%
      for non-drug addicts. Ninety-five of the 98 patients used several drugs,
      including buprenorphine for 53 patients. At the beginning of this study,
      buprenorphine had been available in France for 9 months. CONCLUSION: The results
      are to be taken seriously regarding the misuse of this product in this selected
      population (intravenous use, multiple drug use, dealing).

PMID- 10909150
TI  - [Clinical significance of antiribosomal antibodies. Study Group on Autoimmunity
      (GEAI)].
AB  - PURPOSE: Autoantibodies directed against the ribosomal P proteins, P0, P1 and P2
      (anti-P), have been related to lupus-related psychosis and/or depression. The
      diagnostic value of antibodies directed against other ribosomal proteins or 28S
      RNA (anti-no-P) remains unknown. A multicenter study including ten centers
      belonging to the study group for autoimmune diseases (GEAI) was conducted in
      order to determine the diagnostic value of anti-P and anti-no-P antibodies in a
      large population of patients. METHODS: The patients were selected on the basis of
      the presence of serum anti-ribosomal antibodies detected by indirect
      immunofluorescence (IF) on rat liver/kidney/stomach/pancreas sections and human
      HEp2 cells. The clinical course of all patients was studied using a predetermined
      survey. The specificity of anti-P antibodies were determined by Western blot.
      RESULTS: Anti-ribosomal antibodies were found in 82 patients. Fifty-five of them
      had systemic lupus erythematosus and 27 had another disease. Only 54% of the anti
      ribosomal antibodies detected by IF were anti-P and were found in 69% of the
      patients with systemic lupus erythematosus. Anti-no-P antibodies (46%) were
      preferably detected in patients who suffered from another disease (78%). In
      patients with systemic lupus erythematosus, neurological and psychiatric
      disorders were more frequent in the no-P group (47% vs. 16%, P < 0.01) than
      arthritis, which was found more frequently in the P group (78% vs. 53%, P <
      0.05). CONCLUSION: Anti P antibodies do not constitute a specific diagnostic
      marker of systemic lupus erythematosus, and lupus-related neuropsychiatric
      disorders would be preferably associated with the presence of anti no-P
      antibodies.

PMID- 10909151
TI  - [Diagnostic strategy in amyloidosis].
AB  - INTRODUCTION: The diagnosis of amyloidosis is a four-step strategy requiring: 1)
      a high degree of suspicion, as the clinical presentation of the disease is very
      polymorphous; 2) the biochemical nature of the disease; 3) the evaluation of the
      disease spread and 4) how it evolves. EXEGESIS: Simple and noninvasive biopsies
      usually make it possible to diagnose amyloidosis. Available treatments of
      generalized amyloidosis require an exact characterization of the nature of
      amyloid deposits, which is based on the clinical context, immunohistochemical
      analysis of amyloid deposits, and genetic testing. CONCLUSION: Management of
      amyloidosis should be improved by better characterization of amyloid deposits.
      This would result in epidemiological data which are currently lacking.

PMID- 10909152
TI  - [Alzheimer's disease: from pathology to preventive methods?].
AB  - INTRODUCTION: Sporadic Alzheimer's disease is the most frequent form of dementia
      and appears to be associated with increasing age and certain genetic and
      environmental factors. Some studies have recently been published on potential
      protective factors. CURRENT KNOWLEDGE AND KEY POINTS: Several genes appear to be
      involved; one of the most common is the ApoE4 allele on chromosome 19. The
      physiopathology is not elucidated, but recent studies have shown a protective
      effect for NSAIDs, estrogen, nutritional factors (vitamins E, B6 and B12) as well
      as some biochemical amino acids (homocysteine). FUTURE PROSPECTS AND PROJECTS:
      Interventional studies are now in progress and some preventive approaches will
      soon be available.

PMID- 10909153
TI  - [Development of a predictive model for respiratory isolation of patients
      suspected of having pulmonary tuberculosis].
AB  - INTRODUCTION: As numerous nosocomial outbreaks of pulmonary tuberculosis have
      been reported during the last two decades, prompt identification and effective
      isolation of contagious patients should be made a priority in tuberculosis
      control policies. There is a need to develop a predictive model which would allow
      prompt recognition and isolation of smear-positive patients. CURRENT KNOWLEDGE
      AND KEY POINTS: Various authors have attempted to improve the respiratory
      isolation policies for patients suspected of having pulmonary tuberculosis. A
      French multicenter prospective study of 211 patients suspected of having
      pulmonary tuberculosis established that: 1) the current respiratory isolation
      policy of suspected pulmonary tuberculosis needs improvement (sensitivity =
      71.4%; i.e., 28.6% of smear-positive patients are admitted without isolation) and
      2) better interpretation of clinical and radiological data available on patient
      admission could improve the adequacy of respiratory isolation. Univariate
      analysis showed that predictive factors of pulmonary tuberculosis were chest X
      rays (P < 0.00001), symptoms (P = 0.0004), age (mean: 40.8 years for TB vs. 47.5
      for non-TB, P = 0.04), HIV infection (10.6% vs. 28.7%, P = 0.01), immigrant (72%
      vs. 55%, P = 0.03) and BCG status (P = 0.025), while multivariate analysis
      demonstrated that chest X-ray pattern (P < 0.00001), HIV infection (P = 0.002)
      and symptoms (P = 0.009) were independent predictive factors. FUTURE PROSPECTS
      AND PROJECTS: From these data, a model was proposed and evaluated in the
      derivation cohort using the receiver operating characteristics (ROC) curve. We
      retrospectively studied the predictive model in two populations different from
      the one from which it was derived. The model would have improved sensitivity of
      the respiratory isolation policy from 71.4% (current respiratory isolation
      policy) to 82.4% and 91.1%, respectively. Prospective, multicenter studies are
      requested to establish the value of such a predictive model in improving the
      respiratory isolation policy for patients suspected of having pulmonary
      tuberculosis.

PMID- 10909154
TI  - [Association between polymyositis and hepatitis C infection. Treatment-related
      difficulties].
AB  - INTRODUCTION: Chronic hepatitis C virus infection is often associated with
      various auto-immune disorders. We report four cases of an association between
      polymyositis and hepatitis C virus infection. The course and the difficulties of
      therapy are discussed. EXEGESIS: Among 510 consecutive patients infected by viral
      hepatitis C, we report four cases of polymyositis. Corticosteroids increased
      serum alanine aminotransferase levels in two cases, leading to severe liver
      injury in one patient. Worsening of polymyositis under interferon-alpha therapy
      was observed in one case. Clinical and biological stability were reported in
      another case. Aggravation of polymyositis with severe muscle weakness and dyspnea
      occurred in two patients after disruption of interferon-alpha treatment.
      Intravenous gamma globulins subsequently improved their condition, without
      biological worsening of viral hepatitis. CONCLUSION: These observations suggest
      an association between hepatitis C virus infection and polymyositis. Because
      corticosteroids can induce adverse effects in the liver, intravenous gamma
      globulins could be used for the treatment of this particular form of
      polymyositis.

PMID- 10909155
TI  - [Infectious osteoarthritis due to Propionibacterium acnes. Two new cases].
AB  - INTRODUCTION: Propionibacterium acnes is an anaerobic germ, usually found as a
      saprophyte of the skin and the mucosa. It may be responsible for iatrogenic or
      spontaneous osteoarhritis. EXEGESIS: We report two new cases of septic arthritis
      induced by P. acnes: a case of iatrogenic spondylodiscitis and a case of
      spontaneous septic arthritis of the lumbar facet joints. The two patients were
      immunocompetent, without acne. CONCLUSION: Except for patients with criteria of
      the SAPHO syndrome (synovitis-acne-pustulosis-hyperostosis-osteomyelitis),
      osteoarthritis caused by P. acnes is increasingly described. The number of these
      infections is probably underestimated because of the technical problems involved
      in isolating P. acnes in the laboratory.

PMID- 10909156
TI  - [Premature cerebral vascular accidents after initiation of steroid therapy in
      Horton disease].
AB  - INTRODUCTION: Steroid therapy remains the standard treatment for giant cell
      arteritis but is sometimes incriminated in the occurrence of ischemic events,
      particularly in the early phase of the disease. EXEGESIS: We report four cases of
      ischemic events observed early after initiation of steroid therapy in giant cell
      arteritis. We also reviewed the literature. CONCLUSION: Though the close temporal
      relationship between the initiation of steroids and the occurrence of ischemic
      events suggests a causative link, other factors such as arteritis itself or
      arteriosclerosis would also play a role. Systematic prescription of an
      anticoagulant should be discussed at the initial phase of treatment of giant cell
      arteritis.

PMID- 10909157
TI  - [A bulky tumor of the apex].

PMID- 10909158
TI  - [An uncommon cause of venous thrombosis].

PMID- 10909159
TI  - [Chest pain potentially induced by perindopril].

PMID- 10909160
TI  - [Enterobacterial native valve endocarditis in the intensive care unit: report of
      two cases].

PMID- 10909161
TI  - [Neonatology throughout Europe--accreditation].

PMID- 10909162
TI  - [A new method for self assessment of the pH value of vaginal secretions using an
      indicator-coated panty liner--initial preliminary report].
AB  - BACKGROUND: The measurement of the pH-value in the secretions of the vagina is
      one of the most important early diagnostic methods to recognize disturbances of
      the vaginal milieu in order to prevent the very early premature deliveries. Up to
      now, within the framework of a prenatal care program, the acidity of the vagina
      was assessed by the women themselves "invasively" by introduction of a special
      indicator device (pH-strips or disposable pH-measuring gloves). Now we have
      developed a possibility to assess the pH-value just by simple inspection of an
      indicator coated panty liner, which is worn for a couple of hours. The results
      can be assessed by comparing the color of the indicator with a standard scale.
      RESULTS: It was possible to assess the pH in 77% of 133 parallel measurements
      comparing the pH of the vagina and of the indicator coated panty liner in 19
      pregnant women. An agreement of the two methods for pH-determination was found in
      66%. CONCLUSIONS: These results are encouraging and further investigation in
      larger series of cases are in progress.

PMID- 10909163
TI  - [Advantages of water filtered over conventional infrared irradiation in
      neonatology].
AB  - BACKGROUND: When infrared (IR) radiation is conducted through water, its long
      wave parts (called IR-B and IR-C) are filtered out in favour of the short-wave IR
      A band. Since the former are normally absorbed in the outer layers of skin, water
      filtering results in a reduced risk of superficial burns and a better penetration
      into tissues. This effect which in solar radiation results from its passing
      through the water vapour of the earth's atmosphere, has now been successfully
      imitated in radiant heaters. In this study, the potential benefits of water
      filtered as compared to conventional infrared radiation in obstetrics and
      neonatology were examined. MATERIALS AND METHODS: To this end, three
      methodological approaches were made, namely: 1. Comparative physical measurements
      of radiant power density in several clinically used IR-sources, 2. physiological
      simulation experiments on the surface and depth effects of either type of
      radiation (performed on human adults and an artificial tissue phantom), and 3.
      clinical observations on the protective effects of the novel IR-A-radiators in
      incubator nursing and primary care of preterm neonates. RESULTS AND DISCUSSION:
      Although the absolute radiant power density was equivalent in a conventional and
      a novel heating device, the IR-A radiation proved to result in a markedly reduced
      superficial overheating of tissues. In addition, it exceeded conventional IR
      radiation in its ability to pass through incubator walls, thus lowering the risk
      of cooling in preterm neonates during nursing procedures. Moreover, when used as
      a complementary source of heat in the delivery room, IR-A radiation exerted a
      preventive effect against hypothermia during the subsequent transport of patients
      to the neonatal intensive care unit, probably due to the rapid build-up of heat
      deposits in peripheral tissues. CONCLUSIONS: In view of these benefits which are
      reinforced by a greatly diminished evaporation effect, water-filtered IR
      radiation seems to make a promising contribution to the thermal protection of
      preterm neonates.

PMID- 10909164
TI  - [A new vacuum extraction system with a ball joint and detachment warning--in
      vitro studies and clinical use].
AB  - BACKGROUND: The vacuum extractor is used in about 5% of deliveries. It is
      associated with a lower maternal morbidity than is forceps extraction. On the
      other hand, cephalhematomas, hyperbilirubinemia and cerebral hemorrhages in the
      baby are observed more frequently. The sudden detachment of the vacuum extractor
      with appreciable fluctuations in intracranial pressure in the baby is especially
      dangerous. In order to improve the conventional Malmstrom system, we have
      developed a new vacuum extractor and investigated its handling in vitro and in
      clinical application. PATIENTS AND METHODS: The essential constructional
      principle of the new vacuum extractor consists in a pivot lowered by ball
      bearings and a volume reduction of one third. Moreover, in two-chamber vacuum it
      is possible to give a warning of sudden detachment. The possible tractional force
      in kiloponds was determined at various angles (0 degree, 15 degrees, 30 degrees
      und 45 degrees) comparing the Malmstrom extractor with the new one and two
      chamber system in a standardized apparatus. In addition, the new vacuum extractor
      was also used clinically in 43 women; besides the obstetric parameters, the
      handling was also appraised. RESULTS: In the in-vitro experiments, a distinct
      decrease of the possible tractional force with increasing angles was shown for
      the Malmstrom extractor (0 degree--15.7 kp, 15 degrees--12.7 kp, 30 degrees--8.6
      kp, 45 degrees--7.3 kp). The values for the new one-chamber system were
      significantly greater from a tractional angle of 15 degrees (0 degree--15.6 kp,
      15 degrees--14.4 kp, 30 degrees--14.0 kp, 45 degrees--13.8). The clinical
      application of the new vacuum system was unproblematic and confirmed the
      feasibility of good traction. A very much smaller caput succedaneum was found in
      the baby. Especially in the training situation, the warning system enables a good
      surveillance before sudden detachment, but reduces the possible tractional force.
      CONCLUSIONS: The new vacuum system appears to enable the vaginal surgical
      delivery to be improved compared to the conventional Malmstrom extractor. After
      these promising approaches, a multicenter study was commenced in order to enable
      better evaluation of their clinical significance.

PMID- 10909165
TI  - [Psychosocial management of a new pregnancy after sudden infant death (SID)-
      results of a long-term study of 115 families].
AB  - BACKGROUND: Every subsequent pregnancy after the loss of a child due to Sudden
      Infant Death (SID) causes highly anxious parents. The aim of this investigation
      was to point out which feelings and experiences have to be considered as
      influencing factors for a following pregnancy--besides being afraid of a repeated
      loss. The overlapping fixing of our aim was to develop some proposals and
      recommendations for a capable accompanying during a subsequent pregnancy.
      MATERIALS: The base of the evaluation were 789 consultations during long-term
      cares of 115 families affected by Sudden Infant Death (SID). When their children
      died because of SID 9 of all the mothers were pregnant again. In the families
      which were cared for half-a-year or longer (n = 80), 47 (58.7%) subsequent
      pregnancies became known. All gravidities occurred within one year after SID
      except two cases. RESULTS: We found a strong exigency for information, structure
      and protection during the whole pregnancy. This fact can be deducted from a high
      potential of anxiety and fear within the parents. Furthermore, our investigation
      revealed considerable doubts of the mothers about their parental competence and
      altered, but still intensive affects of grief yet confidence and great joy as
      well. Besides, we also observed problematic social experiences, as e.g. hushing
      up of the dead child or a lacking acceptance of grief by the social environment.
      CONCLUSIONS: A supporting and reliefing accompanying during a subsequent
      pregnancy comprises a continuous enlightenment of parents by being honest and
      open even in giving unpleasant and burdensome informations. It is recommended to
      show understanding for the exceeding anxieties of the parents, to offer them more
      possibilities of examinations and conversations as usually appropriate and to
      talk to them about their dead child and grief. Often the arrangement of contact
      to a parent-self-help association is the essential offer of support.

PMID- 10909166
TI  - [Sacrococcygeal teratoma in obstetrics].
AB  - MATERIALS/METHODS: 5 fetuses with prenatally diagnosed sacrococcygeal teratoma at
      the Department of Prenatal Diagnosis and Therapy during a 30-month period.
      Modified splint technique according to Duzin, following a Pfannenstiel's incision
      in 4 cases. RESULTS: 4 infants with uninjured tumor could be transferred to
      pediatric surgery for treatment. CONCLUSIONS: The modified splint technique
      according to Duzin can be applied particularly in the case of a big tumor.

PMID- 10909167
TI  - [Effect of the dopamine antagonist metoclopramide on uterine contraction].
AB  - BACKGROUND: Because of its activity on the gastro-intestinal tract metoclopramide
      is used also in pregnancy, though nothing is known about its effect on the
      pregnant uterus. Therefore it was of interest to look after a change in uterine
      activity after the application of metoclopramide in a clinical relevant dose.
      MATERIALS AND METHODS: 24 strips from pregnant uteri were removed during a
      cesarean section, brought into an organ chamber and changes of spontaneous
      activity after the application of metoclopramide were measured. RESULTS: A highly
      significant decrease of uterine activity was observed. CONCLUSIONS: It was
      demonstrated that metoclopramide, in contrast to stomach and ureter, exerts not a
      tonifying but a relaxant effect on the uterus.

PMID- 10909168
TI  - [Specific immunotherapy (hyposensitization) with insect venom in pregnancy].
AB  - BACKGROUND: Pregnancy typically prohibits the specific immunotherapy (SIT) of
      various allergic conditions, with the exception of pre-existing Hymenoptera venom
      allergies. International consensus currently recommends the continuation of a
      well-tolerated SIT with insect venom during pregnancy, since there is a
      significant risk of anaphylaxis after insect stings with potentially dismal
      outcomes for mother and fetus. CASE REPORT: We report on a 28-year old woman,
      becoming pregnant during specific immunotherapy with Hymenoptera venom. SIT was
      continued during pregnancy and a premature birth occurred at the 24th week.
      DISCUSSION AND CONCLUSION: Unfortunately, there are still conflicting opinions in
      Germany regarding SIT during pregnancy, and the decision to perform such therapy
      is entirely based on knowledge and/or level of comfort of the primary physician.
      Thus, obstetricians should closely work together with an allergologist in cases
      of pregnant women with insect sting allergies.

PMID- 10909169
TI  - [Palivizumab--a monoclonal antibody for passive immunoprophylaxis of respiratory
      syncytial virus infections].
AB  - RSV is the most common cause of lower respiratory tract infections in infants.
      The humanised monoclonal antibody has been developed for prevention of serious
      lower respiratory tract disease caused by RSV. Palivizumab specifically inhibits
      subtypes A and B. In a large, multicenter, double-blind, randomised trial in 1502
      infants at high risk of RSV infection, intramuscular palivizumab 15 mg/kg reduced
      the incidence of RSV-attributable hospitalization by 55% compared with placebo.
      Palivizumab was well tolerated. In Germany palivizumab prophylaxis should be
      considered only for high risk premature infants and high risk infants with
      chronic lung disease if the local rate of hospitalization attributable to
      confirmed RSV infection is frequent.

PMID- 10909170
TI  - Structure of cytomatrix and nuclear matrix revealed by embedment-free electron
      microscopy.
AB  - Embedment-free electron microscopy (EFEM) is a new method which allows the
      visualisation of cytoskeleton in whole-mounted cells. In this study we employed
      EFEM to investigate the structure of cellular scaffolds in glioma C6 cell line.
      The cells were extracted with Triton X-100 that dissolves phospholipids in the
      membranes and removes most of cytoplasmic soluble proteins. The DNA and nuclear
      histones were removed with DNase I and high-salt buffer, respectively. The
      remaining cellular frameworks were temporary embedded in diethylene glycol
      distearate (DGD), sectioned and observed in transmission and scanning electron
      microscope after the removal of DGD. The predominant structure was the extensive
      meshwork of 10-20 nm filaments in the cytoplasm (cytomatrix) and 15-30 nm
      filaments in the nucleus (nuclear matrix). The 5 nm filaments, presumably
      corresponding to the actin filaments, were present in the cytomatrix, but not in
      the nuclear matrix. Moreover, the ultrathin (3 nm) filaments, connecting other
      cytoskeletal components were detected. Those are possibly identical with the
      previously described plectin filaments. For the first time we report the
      occurrence of ultrathin filaments in the nuclear matrix. Thus, in a addition to
      the well known cytoskeletal components (microtubules, intermediate filaments,
      actin microfilaments) EFEM showed a new type of filaments (the ultrathin
      filaments) in the cytomatrix and nuclear matrix. Further immunocytochemical
      studies are needed to determine the biochemical identity of the filaments
      observed in EFEM.

PMID- 10909172
TI  - The protective role of astroglia in the early period of experimental lead
      toxicity in the rat.
AB  - Although the clinical manifestations of lead (Pb) neurotoxicity are documented,
      the subcellular mechanisms of its action are still an open question. The purpose
      of this study was to assess the function of nerve ending particles after acute
      lead exposure and to investigate whether it exerts a toxic effect on astroglial
      functions. The studies were performed using the rodent model of acute lead
      toxicity. Cellular fractions were used in biochemical measurements--synaptosomes
      and glial plasmalemmal vesicles (GPV). Since a procedure for the isolation of the
      fraction of astroglial origin has been developed, it becomes possible to
      investigate lead-astroglia interactions after in vivo exposure. It is of
      importance because most of the studies concerning lead toxicity were performed
      using astroglial culture systems. It was found that the uptake of glutamate (Glu)
      to the synaptosomes was lowered and KCl-dependent release was increased,
      suggesting the impairment of glutamatergic transmission leading to the elevation
      of extracellular amino acid concentration. In contrast, glutamate uptake to the
      GPV fraction was significantly elevated. The activity of the marker enzyme-
      glutamine synthetase (GS) was also significantly increased in the GPV fraction.
      The activation of glial functions suggest a regulatory role for these cells in
      the early period of acute lead toxicity.

PMID- 10909171
TI  - Respiratory effects of capsaicin occur beyond the lung vagi in anaesthetized
      rats.
AB  - The effects of an intravenous capsaicin challenge on the respiratory pattern and
      ventilation were studied in 15 urethane/chloralose-anaesthetized, spontaneously
      breathing rats. Bolus injection of capsaicin at a dose of 5 micrograms/kg into
      the right femoral vein evoked respiratory arrest in all animals (both prior to
      and after bilateral midcervical vagotomy), which effect was abolished by
      ruthenium red pretreatment. Breathing that followed the apnoea was of enlarged
      tidal volume and initially increased respiratory rate, which resulted in an
      augmented ventilation. The capsaicin-induced respiratory changes were independent
      of vagal integrity and may depend on stimulation of vanilloid receptors within
      the nodose ganglia.

PMID- 10909173
TI  - Involvement of nitric oxide in regulation of the medullary respiratory rhythm in
      neonatal rats.
AB  - The NADPH-diaphorase (as a neuronal NO-synthase) reactivity in the medullary
      structures of the respiratory rhythm (RR) generator and the role of NO in the
      regulation of respiratory activity in the phrenic nerve of artificially
      superfused semi-isolated medulla-spinal cord preparations were investigated in
      newborn rats. NADPH-diaphorase positive neurons were found in all nuclei of both
      dorsal and ventral respiratory groups of neurons. The maximal density of stained
      cells was present within the rostral part of the ventrolateral medulla (VLM), in
      the region of the lateral paragigantocellular reticular nucleus. It was found
      that endogenous NO mediates the mechanism of tonic inhibitory control of the RR
      frequency located in the rostral VLM under normal and hypoxic conditions, and
      appears to be involved in generation of the basic RR by the more caudal
      structures of VLM. It was shown that NO biosynthesis mediates the effect of NMDA
      receptors activation on the RR.

PMID- 10909174
TI  - Effects of DAGO on the rodent hippocampal evoked potentials using different
      perfusion solutions.
AB  - Opioid receptor agonists exert excitatory effects in the hippocampus by
      inhibiting GABA release. We report that the mu-opioid agonist, DAGO, increases
      the amplitude of the population spikes (PS) measured in the stratum pyramidale of
      the CA1 cell layer in mouse and rat hippocampal slices perfused with an
      artificial cerebrospinal fluid (ACSF), but not when perfused in Krebs solution.
      The GABAA agonist, 3-APS, induces inhibitory responses when perfused in either
      ACSF or Krebs. Also, the field excitatory postsynaptic potentials (EPSP) measured
      on stratum radiatum do not differ when the slice is perfused with either ACSF or
      Krebs. The increase in the amplitude of the PS induced by DAGO is not obtained
      when perfused in a modified. ACSF whose concentration of MgSO4 was lowered to its
      concentration in the Krebs solution (from 2.4 mM to 1.2 mM). Thus, changes in the
      concentration of MgSO4 seem to be responsible for the different responses induced
      by DAGO.

PMID- 10909175
TI  - Deterministic brain oscillations in the magnetoencephalogram.
AB  - Determinism is a special property of some systems and is defined by its state
      space behavior in which the trajectories in time never intersect. Whether or not
      determinism exists in brain activities is a question that may be resolved by
      analysis of the dynamical properties of the electroencephalogram (EEG) or
      magnetoencephalogram (MEG). We will show that even though there are strong
      nonstationarities in most brain behaviors, small epochs of deterministic dynamics
      can still be observed. We will also show that the local Lyapunov exponents are
      measures that can demonstrate smooth transitions into these deterministic states.

PMID- 10909176
TI  - Hyposensitivity to amphetamine following exposure to chlorphenvinphos--protection
      by amphetamine preexposure.
AB  - We investigated the effect of an acute exposure to chlorphenvinphos (CVP), an
      organophosphate anticholinesterase, on amphetamine-induced open-field locomotion
      in rats. CVP was administered in a single i.p. dose of 1.0 mg/kg (1/10 of the
      LD50). All animals were challenged with 1.0 mg/kg amphetamine (AMPH) three weeks
      after the CVP exposure, i.e. after a time sufficient for acetylcholinesterase
      recovery. Some rats were also given AMPH three weeks before the CVP exposure. In
      rats challenged with AMPH only once after the CVP exposure, AMPH-induced open
      field locomotion was significantly reduced. Such an effect was not observed in
      rats given AMPH three weeks before the CVP exposure. The results suggest that a
      single CVP exposure may result in persistent dopaminergic hyposensitivity, and
      that an amphetamine pretreatment may protect the rat against this effect.

PMID- 10909177
TI  - Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on cyclic
      AMP formation in the duck and goose brain.
AB  - Two molecular forms of pituitary adenylate cyclase-activating polypeptide
      (PACAP), i.e., PACAP27 and PACAP38 (0.0001-1 microM), as well as vasoactive
      intestinal polypeptide (VIP; 0.1-3 microM), have been studied for their effects
      on cyclic AMP formation in the hypothalamus and cerebral cortex of duck and
      goose. All three peptides concentration-dependently stimulated cyclic AMP
      production in the tested brain regions of 2-3-weeks-old (young) ducks, with VIP
      showing at least one order of magnitude weaker activity than PACAP. This
      characteristics suggests the existence in the duck's brain of adenylyl cyclase
      linked PAC1 receptors. Both forms of PACAP also stimulated the nucleotide
      formation in the cerebral cortex and hypothalamus of 5-6-months-old (adult) ducks
      or geese grown under natural environment. The peptides-evoked effects in adult
      and young ducks were comparable, and clearly greater than those found in adult
      geese. The present data extend our recent observations made on chicks, and
      suggest PACAP to be a potent stimulator of the cyclic AMP generation in the avian
      central nervous system.

PMID- 10909178
TI  - Amyloid beta protein affects poly(ADP-ribose) polymerase activity in PC-12 cells
      in culture.

PMID- 10909179
TI  - Axoplasmic localisation of the NF kappa B p65 subunit in the rat brain.

PMID- 10909180
TI  - Involvement of single unit activity in inferotemporal and perirhinal cortices in
      recognition memory of visual objects in the macaque.
AB  - Recognizing objects from the past is a vitally important ability for everyday
      live. The studies of brain mechanisms responsible for visual recognition memory
      suggest that the modulation of single unit activity in the inferotemporal and
      perirhinal cortices could be an important part of the neuronal substrate of
      recognition memory. In this review, I will describe Stimulus Specific Adaptation
      (SSA)--the reduction in neuronal response to previously viewed objects. The
      experimental tasks in which SSA is observed will be presented, along with the
      possibility that SSA may be enhanced by saccadic exploration of visual scene.
      Next, I will demonstrate that under special circumstances (partially split-brain
      preparation) monkeys could recognize the re-presentation of visual images without
      the concomitant appearance of SSA. The most promising alternative candidate for
      neuronal mechanism involved in recognition memory is delay activity--an increased
      frequency of cell firing in the time between the initial presentation of an image
      and its subsequent re-presentation. In order to determine if delay activity is
      important for recognition we have started to investigate the effects on
      recognition memory of disrupting delay activity by electrical stimulation.
      Preliminary results indicate a positive correlation between a reduction in delay
      activity and a decrease in recognition performance.

PMID- 10909181
TI  - Integration of low-frequency sleep oscillations in corticothalamic networks.
AB  - The corticothalamic system acts as a complex network in promoting the various
      oscillatory patterns (slow oscillation, spindles, delta) that characterize the
      state of quiet sleep. Local synchronizing mechanisms of any of the above
      mentioned oscillations occur at the site of their genesis, thalamic or cortical.
      These mechanisms are assisted by the wide-range, synchronized occurrence of the
      cortical slow oscillation, which finally produces the coalesced picture of slow
      wave sleep EEG. Multisite, simultaneous intracellular and field potential
      recordings in cat, as well as EEG recordings in human were performed in order to
      assess the state of synchrony and the propagation of various sleep rhythms in the
      corticothalamic network.

PMID- 10909182
TI  - Beta activity: a carrier for visual attention.
AB  - The alpha (8-13 Hz), beta (15-25 Hz) and gamma (30-60 Hz) bands of the EEG have
      been long studied clinically because of their putative functional importance. Old
      experimental results indicate that repetitive stimulation of the visual pathway
      evokes synchronous responses at the cortical level with a gain that depends on
      frequency; oscillations within relevant bands are less damped at subsequent
      processing levels than others. Our current results show in the cat that cortico
      geniculate feedback has a build-in potentiation mechanism that operates at around
      the beta frequency and activates thalamic cells thus lowering the threshold for
      visual information transmission. We have also shown that enhanced beta activity
      is propagated along this feedback pathway solely during attentive visual
      behavior. This activity consists of 300-1,000 ms bursts that correlate in time
      with gamma oscillatory events. Beta-bursting activity spreads to all investigated
      visual centers, including the lateral posterior and pulvinar complex and higher
      cortical areas. Other supporting data are discussed that are concerned with the
      enhanced beta activity during attentive-like behavior of various species,
      including humans. Finally, we put forward a general hypothesis which attributes
      the appearance of oscillations within the alpha, beta and gamma bands to
      different activation states of the visual system. According to this hypothesis,
      alpha activity characterizes idle arousal of the system, while beta bursts shift
      the system to an attention state that consequently allows for gamma
      synchronization and perception.

PMID- 10909183
TI  - Cortical synchronization suggests neural principles of visual feature grouping.
AB  - Compositions of visual scenes are related here to neural signals in visual cortex
      and to cortical circuit models to understand neural mechanisms of perceptual
      feature grouping. Starting from the hypothesis that synchronization and
      decoupling of cortical gamma-activities (35-90 Hz) define the relations among
      visual objects, we concentrate on synchronization related to (1) static retinal
      stimulation during ocular fixation, and (2) transient stimulation by sudden
      shifts in object position. The synchronization hypothesis has been tested by
      analyzing signal correlations in visual cortex of monkeys with the following
      results: Static retinal stimuli induce loosely phase-coupled gamma-activities
      among neurons of an object's cortical representation. Patches of gamma
      synchronization become decoupled across the representation of an object's
      contour, and thereby can code figure-ground segregation. Transient stimuli evoke
      synchronized volleys of stimulus-locked activities that are typically non
      rhythmic and include low frequency components in addition to those in the gamma
      range. It is argued that stimulus-induced and stimulus-locked synchronizations
      may play different roles in perceptual feature grouping.

PMID- 10909184
TI  - Synchronised oscillations of the human sensorimotor cortex.
AB  - Oscillations are a prominent feature of macroscopic human sensorimotor cortical
      activity as recorded non-invasively with electroencephalography (EEG) and
      magnetoencephalography (MEG). The advent of whole-scalp MEG systems allowing
      rapid non-invasive recording from the entire cortex and accurate localisation of
      neural sources, and the development of refined signal analysis methods are
      important factors that led to an increasing interest in studies of sensorimotor
      oscillations during the last 10 years. Investigations on healthy subjects
      revealed frequency-specific localisation and modality-specific reactivity of 10
      Hz and 20 Hz sensorimotor oscillations. Task-specific coherence between motor
      cortical and electromyographic oscillations, reflecting cortico-motoneuronal
      coupling, point towards a functional role of precentral oscillations in the
      cortical control of voluntary movements. Furthermore, abnormal cortico
      motoneuronal coupling may underlie clinical symptoms of motor disorders, such as
      tremor. Thus, investigation of oscillatory sensorimotor activity proceeds from
      phenomenology to function and provides an interesting approach to address
      questions in human motor physiology and pathophysiology.

PMID- 10909185
TI  - Physiological basis of pathophysiological brain rhythms.
AB  - Focal epilepsy may be induced acutely in the brain in vivo by measures which
      reduce inhibition or enhance excitation. Although the various models involve
      different mechanisms causing the epilepsy, their epileptiform discharge patterns
      vary only little. Intracellular analyses in vivo and in vitro reveal that the
      cellular hallmark of epileptic discharge, the paroxysmal depolarization shift, is
      followed by a giant hyperpolarization. The latter is comprised of several,
      overlapping, components with different durations, including calcium dependent
      potassium currents and GABA dependent inhibitions. Relative reduction of one
      inhibitory component is compensated by other inhibitory components. In epilepsy
      caused by reduction of GABAergic inhibition, the absolute duration and amplitude
      of GABAergic inhibition may even be increased in comparison to the responses
      following afferent stimulation under control conditions since the excitatory
      drive of the paroxysmal discharges on the interneurons is strongly increased. In
      some interictal discharge patterns, the enhanced inhibitions within the focus
      determine the refractory periods of the focus. The latter is paced by neurons
      from the perifocal area which show a shorter inhibition associated with the
      interictal epileptic event. The discharge pattern of the focus may switch to
      other patterns, either spontaneously, or as entrained by external stimulation.
      Such changes are caused e.g. by progressive potassium accumulations in the
      extracellular space with critically small intervals of the epileptic events. It
      is concluded that the epileptiform discharge patterns reflect intrinsic
      properties of the brain, and do not very well reflect the mechanism of action of
      the epileptogenic model. The brain is thus equipped with inherent mechanisms
      which favor rhythmic epileptiform discharges under certain conditions.

PMID- 10909186
TI  - New NO donors with antithrombotic and vasodilating activities, Part 27. Azide
      oximes and 1-hydroxytetrazoles.
AB  - Eleven azide oximes were prepared and tested for their antiplatelet (in vitro),
      antithrombotic, and blood pressure lowering activities. Nine of them inhibited
      the aggregation of blood platelets (Born test, inducer collagen) with IC50 values
      between 10 and 50 microM. The most active compounds i.e. azido-4
      nitrophenylbenzaldoxime (2h) had an IC50 = 2 microM. Nine azide oximes exhibited
      significant antithrombotic properties. The most active compounds were 2h and 2c
      (azido-4-methylphenylbenzaldoxime) with an inhibition of thrombus formation above
      20% in arterioles after a single p.o. dose of 60 mg/kg. Both compounds lowered
      the blood pressure in spontaneously hypertensive rats by 11% (2h) or 5% (2c),
      respectively. Seven azide oximes were rearranged to the title tetrazololes which
      however showed smaller antithrombotic effects. In separate in vitro experiments
      at 37 degrees C it could be demonstrated that azide oximes release nitric oxide
      (conversion rate approximately 10%.h-1) and nitrosohydrogen (conversion rate
      approximately 2%.h-1). This makes it appear probable that the above effects are
      mediated by these molecules.

PMID- 10909187
TI  - Azole antifungal agents related to naftifine and butenafine.
AB  - The methyl group of naftifine (1) and butenafine (2) was replaced by an azolic
      nucleus to obtain the new compounds 3-8 which exhibit the characteristics of both
      allylamine (or benzylamine) and azole antifungals. The title compounds were
      evaluated in vitro against several pathogenic fungi responsible for human
      disease. Among these, compounds 5, 6, and 8 were found to inhibit the growth of
      dermatophytes with a potency comparable to that of naftifine. The synthetic
      sequence includes the preparation of aminoazole Schiff bases, reduction, and
      alkylation of the corresponding secondary amines.

PMID- 10909188
TI  - Synthesis, analgesic activity, and binding properties of some epibatidine analogs
      with a tropine skeleton.
AB  - A series of epibatidine analogs and their positional isomers bearing an 8
      azabicyclo[3.2.1]octane moiety is described. Also some of their simplified
      analogs bearing a 3-piperidine moiety are reported. Their receptor binding
      profiles (5-HT1A, 5-HT1B, M1, M2, neuronal nicotinic receptor) and analgesic
      activity (hot plate, acetic acid induced writhing) have been studied. Some of the
      compounds, especially those containing an 8-azabicyclo[3.2.1]oct-2-ene moiety
      possess high afinity for the nicotinic cholinergic receptor. The most
      analgesically active compounds are also highly toxic. Optimized structures (PM3
      MOPAC, Alchemy 2000, Tripos Inc.) of compounds 1-9 were compared with that of
      epibatidine.

PMID- 10909189
TI  - Synthesis and antioxidant activity of flavanoid derivatives containing a 1,4
      benzodioxane moiety.
AB  - Flavanoids bearing a 1,4-benzodioxane moiety [rac-15a, -16a, -17, -18, (-)-15a, (
      )-16a] were prepared from protocatechualdehyde (5) and tested for inhibitory
      activity on the superoxide anion (O2.-) release by human polymorphonuclear
      leukocytes (PMNLs).

PMID- 10909190
TI  - Synthesis and antitumour activity of new derivatives of flavone-8-acetic acid
      (FAA). Part 4: Variation of the basic structure.
AB  - A range of 11 derivatives of flavone-8-acetic acid (FAA) in which the structure
      has been substantially altered in different ways have been prepared and their
      anti-tumour activity evaluated in vitro against a panel of human and murine
      tumour cell lines and in vivo against MAC 15A. The generally poor activity
      observed shows that the basic structure cannot be altered much without destroying
      the activity.

PMID- 10909191
TI  - Synthesis and evaluation of the antitumor activity of 2-substituted 1,4-dihydroxy
      9,10-anthraquinones.
AB  - 2-(1-Hydroxyiminoalkyl)-1,4-dimethoxy-9,10-anthraquinones were demethylated to
      produce 2-(1-hydroxyiminoalkyl)-1,4-dihydroxy-9,10-anthraquinones (1,4-dihydroxy
      9,10-anthraquinone, DHAQ), oxime hydroxyl groups were in turn acylated to give
      the corresponding 2-(1-acyloxyiminoalkyl)-DHAQ derivatives. The anti
      proliferative activity of 2-(1-hydroxyiminoalkyl)-DHAQ derivatives was found to
      be dependent on the size of an alkyl chain. Thus, DHAQ analogues with alkyl
      chains longer than heptyl had negligible anti-proliferative activity, whilst
      those compounds possessing shorter chains demonstrated moderate anti
      proliferative activity (ED50, 2.73-19.21 microM). However, the antitumor activity
      as expressed by T/C values did not correlate with the anti-proliferative
      activity; 2-(1-hydroxyiminononyl)-DHAQ with an ED50 value of more than 20 microM
      exhibited potent antitumor activity (T/C, 166%). Only four of the 2-(1
      hydroxyiminoalkyl)-DHAQ analogues showed good antitumor activity (T/C, > 150%); 2
      (1-hydroxyiminobutyl)-DHAQ (T/C, 163%), 2-(1-hydroxyiminopentyl)-DHAQ (T/C, 180%)
      and 2-(1-hydroxyiminononyl)-DHAQ (T/C, 166%). Acylation of the hydroxyl group of
      these oximes enhanced the anti-proliferative activity and antitumor effects; 2-(1
      propanoyloxyiminopropyl)-DHAQ (ED50, 4.41 microM; T/C, 221%) vs. 2-(1
      hydroxyiminopropyl)-DHAQ (ED50, 14.64 microM; T/C, 100%) and 2-(1
      propanoyloxyiminobutyl)-DHAQ (ED50, 2.65 microM; T/C, 202%) vs. 2-(1
      hydroxyiminobutyl)-DHAQ (ED50, 16.43 microM; T/C, 163%).

PMID- 10909192
TI  - Bioanalysis of syn dimeric HIV-1 protease inhibitor N-benzyl 4-aryl-1,4
      dihydropyridine H19: metabolic and cytotoxic properties in Hep G2 cells.
AB  - Syn dimeric N-benzyl 4-aryl-1,4-dihydropyridine H19 is a nonpeptidic HIV-1
      protease inhibitor of the dihydroxyethylene type representing novel C2-symmetric
      inhibitors. Great interest was focussed on the extent of metabolism of these
      novel inhibitory structures as their functional groups are similar to certain
      peptidic and non-peptidic HIV-1 protease inhibitors with poor bioavailability due
      to extensive metabolism. Thus, early characterization of metabolic and toxic
      properties decisively determines the future prospects of those novel HIV-1
      protease inhibitors. Both metabolism and toxicity were evaluated in Hep G2
      monolayers. While no phase-I metabolites were found the extent of conjugation in
      phase-II of biotransformation was poor. Moreover, cytotoxic evaluation of protein
      and DNA decrease and, furthermore, of membrane toxicity characterized the novel
      inhibitors as non-toxic. Consequently, the favourable poor metabolism and non
      toxic properties encourage further development of these novel HIV-1 protease
      inhibitors.

PMID- 10909193
TI  - Mental health services in Connecticut: troubled systems in a time of crisis.

PMID- 10909194
TI  - The use of psychotropic medications in young children: the facts, the
      controversy, and the practice.
AB  - There has been recent concern by the public and physicians alike over reports
      that increasing numbers of young children are being prescribed psychotropic
      medications. The report by Zito and colleagues addressing this subject that
      appeared in the 23 February 2000 issue of JAMA sparked enormous controversy and
      was the impetus for a White House Conference just one month in its wake (20 March
      2000). State and federal agencies have considered legislation to regulate the
      practice of prescribing psychotropic medications to preschool children. Special
      aspects of the use of psychotropic medication in preschool children are reviewed,
      with recommendations for evaluation and treatment decisions. The need for data
      and research in this area is highlighted.

PMID- 10909195
TI  - Electroconvulsive therapy: clinical science vs controversial perceptions.

PMID- 10909196
TI  - Early identification and intervention in psychotic illness.
AB  - Early detection and intervention strategies in persons who present with recently
      developing "prodromal" symptoms that look like early versions of the symptoms of
      psychosis are being investigated at a special outpatient clinic at Yale Medical
      School. The study aims to test whether treatment, including newer antipsychotic
      medication, can treat these symptoms and, in addition, might prevent or delay the
      onset of psychosis. Here we describe the clinic, the study, and the symptoms to
      look for in patients who may be at high risk for becoming psychotic in the near
      future. We also discuss the practical and ethical ramifications of this promising
      new direction in the treatment of serious mental illness.

PMID- 10909197
TI  - Syndrome X, depression, and chaos: relevance to medical practice.
AB  - The low detection rate and undertreatment of depression in general medical
      practice is pervasive. The persistence of this problem suggests that doubt
      remains within elements of the medical profession that depression is a medical
      condition meriting medical treatment, as opposed to an existential state,
      inevitable for the human condition. Depression is a physical and psychological
      clinical disorder which affects every aspect of human physiology. As such it
      deserves consideration as a comorbid medical illness requiring treatment as does
      hypertension in relation to diabetes. This article will illustrate how clinical
      depression is a comorbid medical illness requiring detection and treatment
      through the analysis of depression's impact on two conditions called Syndrome X.
      Conditions labeled Syndrome X in endocrinology and cardiology demonstrate how
      depression amplifies the pathophysiology of endocrine and cardiac disease and
      diminishes functional variability (regularizes variance) found in normal
      physiology.

PMID- 10909198
TI  - Herbal medicines with psychiatric indications: a review for practitioners.
AB  - The use of herbal medicines remains controversial despite their wide use by
      consumers. By U.S. standards few of these products have been sufficiently
      evaluated in scientific studies to determine with certainty their efficacy and
      safety. The authors review the herbal medicines with reputed psychiatric
      indications and discuss the potential adverse events with which physicians should
      be familiar. Whatever their potential benefits, some of these herbal products
      have potentially serious side effects, and many can interact with prescription
      medications. Patients frequently do not tell their physicians about their use of
      alternative medicines, and practitioners must ask specifically about products
      patients may be taking for health promotion and disease prevention as well as for
      the treatment of the presenting complaint.

PMID- 10909199
TI  - Drugs and A.D.H.D.

PMID- 10909200
TI  - Do no harm.

PMID- 10909201
TI  - Regional anesthesia: a century of progress.

PMID- 10909202
TI  - This month's reading in review.

PMID- 10909203
TI  - How much care is good for us?

PMID- 10909204
TI  - Outbreak investigation--a perspective.

PMID- 10909205
TI  - Fish mortality in southeastern Caribbean countries.

PMID- 10909206
TI  - Meeting of the Regional Advisory Committee on Health Statistics.

PMID- 10909207
TI  - Update on yellow fever in the Americas.

PMID- 10909208
TI  - Case definitions. Dengue fever.

PMID- 10909209
TI  - Case definitions. Leptospirosis.

PMID- 10909218
TI  - [Bypass surgery or PTCA in coronary disease? Both methods are rapidly developing;
      continuous quality control is required].

PMID- 10909219
TI  - [Efficient drugs, reconstructive surgery and "heart assist" are alternatives to
      transplantation. It's possible to treat severe heart failure].

PMID- 10909220
TI  - [Fiberoptic endoscopy confirms the cause of upper respiratory obstruction in
      small children. The most common causes to referrals are sleep apnea syndrome and
      inspiratory stridor].
AB  - Guidelines for the clinical investigation of young children with stridor and
      sleep apnea are presented. Clinical examination and flexible videolaryngoscopy
      performed in local anaesthesia are the most important diagnostic tools for this
      group of children. If the impairment is severe or an objective evaluation is
      needed the child should also undergo nocturnal polygraphic recording and lung
      function tests. Out of 43 children examined with flexible videolaryngoscopy 21
      had positive findings, laryngomalacia being the most common diagnosis. Flexible
      videolaryngoscopy is a good complement to laryngoscopy under general anaesthesia.
      It can be performed as early as in the neonatal period.

PMID- 10909221
TI  - [Results following coronary revascularization. 478 patients in a detailed follow
      up].

PMID- 10909222
TI  - [Reconstructive heart surgery is possible also in severe heart failure].
AB  - Patients with severe heart failure due to valvular disease or coronary artery
      disease often benefit from conventional heart surgery even in the presence of
      severe left ventricular dysfunction. If a conventional procedure is not possible,
      left ventricular reconstructive surgery can be of value in selected cases. In
      cases of idiopathic dilated cardiomyopathy, the Batista procedure can improve
      left ventricular function, whereas in patients with ischemic cardiomyopathy, with
      or without left ventricular aneurysm, an endoventricular patch plasty with septal
      exclusion might be of value. Some patients with dilated cardiomyopathy and severe
      mitral regurgitation can benefit from a simplified mitral valvuloplasty.

PMID- 10909223
TI  - [Primary health care costs in connection with heart failure surveyed: increased
      use of ACE inhibitors would be beneficial].

PMID- 10909224
TI  - [Magnetic resonance angiography].
AB  - INTRODUCTION: MR angiography (MRA) is a group of MRI techniques capable of
      producing projectional images of arteries and veins without the use of ionising
      radiation or catheters. MATERIAL AND METHODS: This review describes two of the
      main techniques, time-of-flight (TOF) MRA and phase contrast MRA, that provide
      high signal-intensity vessels due to flow phenomena, and a third main technique,
      contrast-enhanced MRA, which relies on intravenous injection of contrast media.
      Contrary to the iodine-containing x-ray contrast media, the contrast media for
      MRA are not nephrotoxic, making contrast-enhanced MRA a good alternative for
      patients with reduced renal function. MRA is indicated in several vascular areas,
      especially head and neck arteries and veins, the large thoracic and abdominal
      arteries and veins, and the lower extremity arteries. INTERPRETATION: For several
      indications, the sensitivity and specificity of MRA is approaching those of the
      gold standard, x-ray angiography. There are reasons to believe that most
      diagnostic angiographic procedures will soon be performed as MRA.

PMID- 10909225
TI  - [The price doesn't affect the number of orders for laboratory tests].

PMID- 10909227
TI  - [Nutrition in a new millennium. IT--for integrated teaching].

PMID- 10909226
TI  - [Troubled times in care of the elderly. Increasing number of the "oldest old" and
      demented, shortage of general practitioners and lack of clarity with regards to
      locating resources].
AB  - The media image of general breakdown in care of the elderly, replete with
      portrayals of malpractice and maltreatment, is analyzed in the light of changes
      in demographics, care resources and care delivery systems during the past
      decades. A substantial increase in the number of people aged 80 years or more,
      increasing numbers of elderly persons with dementia, deinstitutionalization of
      health care, together with the present economic crisis, place a considerable
      burden on the care system, as illustrated by an increased nursing load, a
      decrease in the number of elderly persons receiving home services, and a
      concentration of support to the most impaired. The author calls attention to the
      need for refined methods for describing care delivery systems, longitudinal
      population based studies, and a national hospital plan. Primary health care,
      already pushed to the limit by dwindling resources and job vacancies, is hard put
      to shoulder the burden of responsibility for the elderly.

PMID- 10909228
TI  - [Cesarean section--a human right?].

PMID- 10909229
TI  - [Adjustment insurance--a way to a quick rehabilitation?].

PMID- 10909230
TI  - [An evening... Reflections on drug utilization].

PMID- 10909231
TI  - [TrioBe--the Medical Products Agency should re-evaluate the information text in
      the Fass!].

PMID- 10909232
TI  - [High homocysteine level is not a risk factor of cardiovascular disease].

PMID- 10909233
TI  - [On pediatric psychiatry, the National Board of Health and Welfare and sexual
      abuse of children].

PMID- 10909234
TI  - 18th Congress of the Hungarian Society of Endocrinology and Metabolism and
      Symposium of the European Federation of Endocrine Societies. June 8-10, 2000.
      Abstracts.

PMID- 10909236
TI  - Inhibition of return and visual search: how many separate loci are inhibited?
AB  - Using a novel sequential visual search paradigm Danziger, Kingstone, and Snyder
      (1998) demonstrated that inhibition of return (IOR) can reside at three spatial
      locations. In the present study, we extended the work of Danziger et al. by
      investigating whether there is a limit to the number of locations that can be
      inhibited in a sequential visual search task. Our study revealed that IOR can be
      measured at a minimum of five locations. The magnitude of the IOR effect was
      largest at the most recently searched location and declined from there in an
      approximately linear fashion. Two models that can account for our data are
      presented.

PMID- 10909235
TI  - A signal detection model predicts the effects of set size on visual search
      accuracy for feature, conjunction, triple conjunction, and disjunction displays.
AB  - Recently, quantitative models based on signal detection theory have been
      successfully applied to the prediction of human accuracy in visual search for a
      target that differs from distractors along a single attribute (feature search).
      The present paper extends these models for visual search accuracy to
      multidimensional search displays in which the target differs from the distractors
      along more than one feature dimension (conjunction, disjunction, and triple
      conjunction displays). The model assumes that each element in the display elicits
      a noisy representation for each of the relevant feature dimensions. The observer
      combines the representations across feature dimensions to obtain a single
      decision variable, and the stimulus with the maximum value determines the
      response. The model accurately predicts human experimental data on visual search
      accuracy in conjunctions and disjunctions of contrast and orientation. The model
      accounts for performance degradation without resorting to a limited-capacity
      spatially localized and temporally serial mechanism by which to bind information
      across feature dimensions.

PMID- 10909237
TI  - Novel popout is an attention-based phenomenon: an ERP analysis.
AB  - When observers are given a brief glimpse of a display containing one novel object
      and three repeated objects, they are often better able to report the location of
      the novel object than the location of any one of the repeated objects. The
      present study contrasted two interpretations of this "novel popout" effect. The
      attention-based interpretation suggests that the novel popout is an attentional
      phenomenon, occurring during the initial processing of the four-object display.
      The retrieval-based interpretation suggests that novel popout is due to
      differential processing occurring when observers are subsequently probed for the
      location of one of the objects in the display. ERP measures recorded while
      subjects performed the novel popout task revealed differences during the initial
      processing of the four-object display but not subsequent to the presentation of a
      localization probe. The findings are most consistent with the attention-based
      interpretation of novel popout, which suggests that attention is rapidly drawn to
      the novel object in an otherwise familiar display.

PMID- 10909238
TI  - Visual marking: evidence for inhibition using a probe-dot detection paradigm.
AB  - Watson and Humphreys (1997, 1998) have recently demonstrated that new objects can
      be prioritized for visual attentional processing by the top-down attentional
      inhibition of old objects already in the field, a mechanism they called visual
      marking. The experiments reported here show that the detection of a dim probe dot
      is impaired when it falls at the location of an old object (Experiments 1 and 3)
      but that this occurs only in conditions in which it is advantageous for subjects
      to mark (inhibit) old objects (Experiment 2). These results further support
      previous work showing that visual marking is based on the inhibition of the
      locations of old objects and that visual marking can be flexibly applied (or
      withheld), depending on the goals of current behavior.

PMID- 10909239
TI  - An object-based cost of visual filtering.
AB  - Although evidence for object-based attention has been reported in a variety of
      paradigms, few studies have examined directly the relationship between efficiency
      in the processing of targets and the number of intervening distractors. In five
      experiments, observers judged whether the vertices of two relevant shapes were of
      the same height. Experiments 1 and 2 manipulated observers' perceptual set so
      that identical stimulus displays were perceived as containing either intervening
      or flanking distractors. The observers were faster when the distractors were
      flanking rather than intervening between the targets. Experiments 3-5 varied the
      number of intervening distractors directly. The observers' response latencies
      correlated positively with the distractor set-size. Because the distractors were
      highly discriminable from the targets and the spatial separation between the
      targets and their interactions with the adjacent distractors were held constant,
      it was unlikely that the differential reaction times across the conditions were
      caused by lateral inhibition or response competitions from the distractors. The
      results suggest the existence of an object-based filtering cost. The implications
      of the present data for attentional selection over noncontiguous regions are also
      discussed.

PMID- 10909240
TI  - Inhibition of return and attentional control settings.
AB  - In the present study, we used a spatial cuing paradigm in conjunction with a
      choice identification task to investigate whether exogenous attentional orienting
      and inhibition of return are affected by attentional control settings. As in
      previous studies (e.g., Folk, Remington, & Johnston, 1992), onset- and color
      defined targets were crossed with uninformative onset- and color-defined cues. As
      expected, when the cue-target stimulus onset asynchrony (SOA) was short (i.e.,
      100 msec), the results showed that exogenous attentional orienting was contingent
      on attentional set; attentional capture occurred in response to a particular cue
      only when the feature that defined the cue also defined the target (Folk et al.,
      1992). More importantly, when the cue-target SOA was long (i.e., 1,000 msec), the
      results showed that the occurrence of inhibition of return was also contingent on
      attentional set, at least partially so; inhibition of return occurred in response
      to onset cues only when they preceded onset targets. In contrast, inhibition of
      return never occurred in response to color cues (at a variety of long SOAs). The
      associations and dissociations that were observed between exogenous attentional
      orienting and inhibition of return are discussed in terms of posterior and
      anterior attention networks in the brain (Posner & Petersen, 1990).

PMID- 10909241
TI  - Stimulus segmentation in the visual search task.
AB  - Four experiments were conducted in order to study the segmentation process in a
      visual search task with relevant stimuli (target and distractors) randomly
      distributed among textural elements. The basic idea was that a parallel
      segmentation process of the relevant stimuli would contribute to the overall
      reaction time independently of the contribution of the number of relevant
      stimuli. In the first experiment, with relevant stimuli and textural elements
      that differed in the orientation of their component lines, texture presence
      interacted with number of relevant stimuli and with target presence. These
      results were not favorable to the parallel segmentation hypothesis. In the second
      and third experiments, in which the relevant and the textural stimuli differed in
      orientation and in the luminance contrast of their component lines, the results
      support a parallel segmentation process for the higher contrast conditions. In
      these experiments, the effect of texture presence was greater on target-absent
      than on target-present trials. Experiment 4 shows that the search can be
      restricted to the high-contrast relevant stimuli when the number of these stimuli
      is constant and the number of textural stimuli changes from trial to trial. The
      present results suggest that the relevant stimuli can be segmented in parallel
      and then submitted to a restricted analysis, even when they are scattered among
      textural stimuli.

PMID- 10909242
TI  - Perceptual integration of motion and form information: evidence of parallel
      continuous processing.
AB  - In three visual search experiments, the processes involved in the efficient
      detection of motion-form conjunction targets were investigated. Experiment 1 was
      designed to estimate the relative contributions of stationary and moving
      nontargets to the search rate. Search rates were primarily determined by the
      number of moving nontargets; stationary nontargets sharing the target form also
      exerted a significant effect, but this was only about half as strong as that of
      moving nontargets; stationary nontargets not sharing the target form had little
      influence. In Experiments 2 and 3, the effects of display factors influencing the
      visual (form) quality of moving items (movement speed and item size) were
      examined. Increasing the speed of the moving items (> 1.5 degrees/sec)
      facilitated target detection when the task required segregation of the moving
      from the stationary items. When no segregation was necessary, increasing the
      movement speed impaired performance: With large display items, motion speed had
      little effect on target detection, but with small items, search efficiency
      declined when items moved faster than 1.5 degrees/sec. This pattern indicates
      that moving nontargets exert a strong effect on the search rate (Experiment 1)
      because of the loss of visual quality for moving items above a certain movement
      speed. A parallel-continuous processing account of motion-form conjunction search
      is proposed, which combines aspects of Guided Search (Wolfe, 1994) and
      attentional engagement theory (Duncan & Humphreys, 1989).

PMID- 10909243
TI  - Change in perceived spatial directions due to context.
AB  - We examined the influence of context on exocentric pointing. In a virtual three
      dimensional set-up, we asked our subjects to aim a pointer toward a target in two
      conditions. The target and the pointer were visible alone, or they were visible
      with planes through each of them. The planes consisted of a regular grid of
      horizontal and vertical lines. The presence of the planes had a significant
      influence on the indicated direction. These changes in indicated direction
      depended systematically on the orientation of the planes relative to the subject
      and on the angle between the planes. When the orientation of the (perpendicular)
      planes varied from asymmetrical to symmetrical to the frontoparallel plane, the
      indicated direction varied over a range of 15 degrees--from a slightly larger
      slant to a smaller slant--as compared with the condition without the contextual
      planes. When the dihedral angle between the two planes varied from 90 degrees to
      40 degrees, the indicated direction varied over a range of less than 5 degrees: A
      smaller angle led to a slightly larger slant. The standard deviations in the
      indicated directions (about 3 degrees) did not change systematically. The
      additional structure provided by the planes did not lead to more consistent
      pointing. The systematic changes in the indicated direction contradict all
      theories that assume that the perceived distance between any two given points is
      independent of whatever else is present in the visual field--that is, they
      contradict all theories of visual space that assume that its geometry is
      independent of its contents (e.g., Gilinsky, 1951; Luneburg, 1947; Wagner, 1985).

PMID- 10909244
TI  - Asymmetry in 3-D perceptual organization: ground-like surface superior to ceiling
      like surface.
AB  - Attneave (1954) and Barlow (1961) proposed that the visual system might increase
      efficiency of representation by preferentially encoding spatiotemporally
      redundant patterns of the external world. The present experiments tested the
      application of this principle to three-dimensional (3-D) perceptual organization,
      capitalizing on the ecological constraint that human observers must frequently
      interact with objects arranged on the ground or on a surface parallel to it
      (Gibson, 1950). Observers performed a task that required them to perceptually
      segregate and search multiple items distributed in depth and embedded within a
      larger, 3-D array of distractors. Stimulus displays were organized to globally
      recede top-away in depth, as if attached to an underlying ground-like surface, or
      bottom-away, as if attached to an overhanging ceiling-like surface; ground-like
      and ceiling-like displays differed only in the direction of disparity gradient
      within the displays. Primary findings revealed superior performance with ground
      like displays, suggesting that spatially and stereoscopically distributed items
      are more easily organized to represent an ecologically representative pattern,
      even when no inherent physical regularities favor that pattern.

PMID- 10909245
TI  - Perception of three-dimensional shape specified by optic flow by 8-week-old
      infants.
AB  - Sensitivity of 8-week-old infants to optical flow specifying the shape of a three
      dimensional object was assessed. Infants viewed kinetic random-dot displays that
      specified three-dimensional cubes. The cubes were identical except for the
      presence or absence of an interior corner. Half of the infants viewed the full
      display. The other half viewed the central region of the displays, where the flow
      specifying the presence or absence of the corner differed. Infants in the full
      view condition looked significantly longer to a novel cube than to the familiar
      cube following habituation. In contrast, infants in the partial-view condition
      looked equally to the novel and familiar cubes, ruling out the possibility that
      infants who viewed the full displays merely discriminated differences in motion
      in the central region of the two displays. These findings suggest that infants as
      young as 8 weeks perceive three-dimensional object shape from optic flow.

PMID- 10909246
TI  - Orientation tuning of shape from shading.
AB  - Four experiments were performed to assess the effect of different orientations
      and direction of lighting on the visual processing of shaded or bipartite disks.
      In the first two experiments, observers were presented with nine different
      shading orientations from 0 degree to 180 degrees. Targets were detected in a
      rapid and parallel fashion for shaded disks when the orientation of the shading
      gradient was not horizontal (90 degrees) or oriented at 67.5 degrees. Search
      asymmetries favoring the detection of "pock" targets over "ball" targets were
      found for all orientations. The search rates for bipartite disks were similar to
      the shaded disks at 0 degree, 22.5 degrees, and 90 degrees but not for
      intermediate orientations, and no search asymmetries were found. These
      differences suggest that shaded displays and bipartite displays are processed by
      different underlying mechanisms. The third experiment showed that the direction
      of the light source (left or right) had no influence on search asymmetries around
      the 90 degrees point. Shading gradient orientation affected magnitude estimates
      of depth in the fourth experiment. These experiments show that the visual
      system's "assumption" of overhead lighting is broadly tuned.

PMID- 10909247
TI  - Three elemental illusions determine the Zollner illusion.
AB  - We have discovered an apparent contraction illusion of acute angles in a special
      form of the Zollner figure at the intersecting angles between 36 degrees and 83
      degrees (i.e., a reversal of the Zollner illusion). The necessary condition for
      this illusion is that inducing lines are long enough and the induced line (test
      line) is single. When an illusory line is used as the induced line, the magnitude
      of contraction increases. Short inducing lines give no illusion or a slight
      expansion of acute angles at the intersecting angle of 45 degrees. We have
      ascertained that the source of this expansion is the narrow region in the
      vicinity of the induced line, whereas the source of the contraction is much
      broader regions. Furthermore, we have discovered another expansion mechanism,
      which is generated by the symmetrical configuration of the standard Zollner
      figure.

PMID- 10909248
TI  - Eye movements and the span of the effective stimulus in visual search.
AB  - The span of the effective stimulus during visual search through an unstructured
      alphanumeric array was investigated by using eye-contingent-display changes while
      the subjects searched for a target letter. In one condition, a window exposing
      the search array moved in synchrony with the subjects' eye movements, and the
      size of the window was varied. Performance reached asymptotic levels when the
      window was 5 degrees. In another condition, a foveal mask moved in synchrony with
      each eye movement, and the size of the mask was varied. The foveal mask
      conditions were much more detrimental to search behavior than the window
      conditions, indicating the importance of foveal vision during search. The size of
      the array also influenced performance, but performance reached asymptote for all
      array sizes tested at the same window size, and the effect of the foveal mask was
      the same for all array sizes. The results indicate that both acuity and
      difficulty of the search task influenced the span of the effective stimulus
      during visual search.

PMID- 10909249
TI  - Where am I looking? The accuracy of video-mediated gaze awareness.
AB  - Participants worked in pairs, with one person gazing at a flat horizontal
      stimulus between them. The other participant estimated where the gazer was
      looking. Experiment 1 used linear scales as gaze targets. The mean root mean
      square error of estimation equates to 3.8 degrees of head-and-eye pan and 2.6
      degrees of tilt. This small error of estimation was essentially the same in a
      video-mediated condition and in one in which a procedure that did not allow the
      estimator to see the head-and-eye movement to the target position was used.
      Experiment 2 obtained comparable gaze estimation performance in face-to-face and
      video-mediated conditions, using a combined pan-and-tilt grid. It is concluded
      that people are very good at estimating what someone else is looking at and that
      such estimations should be practical during video-mediated conversation.

PMID- 10909250
TI  - Processing of sequential tactile patterns: effects of a neutral stimulus.
AB  - The perception of a target pattern may be interfered with by the presentation of
      a nontarget pattern in close temporal and spatial proximity with it. The results
      from previous studies suggested that much of this interference is the result not
      of masking but of response competition, subjects responding with the nontarget
      instead of the target. Using a 4-to-2 paradigm in which four target patterns are
      mapped onto two responses, it was shown that neutral patterns (i.e., patterns
      with no responses associated with them) produce considerable interference. The
      amount of interference is less than that produced by patterns associated with
      incorrect responses but greater than that produced by patterns associated with
      correct responses. The amount of interference produced by neutral patterns did
      not vary as a function of the form of the neutral pattern (Experiments 1 and 2);
      however, the amount of interference did depend on the degree and nature of the
      similarity between the neutral and target patterns (Experiments 3 and 4). The
      results indicate that recent studies have underestimated the amount of
      interference due to masking and overestimated the amount due to response
      competition. Response competition may either hinder or help target categorization
      depending on the nontarget pattern.

PMID- 10909251
TI  - Method of stimulation, mouth movements, concentration, and viscosity: effects on
      the degree of taste adaptation.
AB  - Although sensory adaptation, the gradual loss of sensation during prolonged
      stimulation, has been demonstrated in laboratory taste experiments, a comparable
      loss of taste intensity is not experienced in real-life eating situations. This
      discrepancy may be due to differences in the proximal stimuli or to differences
      in the ways the taste receptors are stimulated. In two experiments, the effects
      of four potentially relevant variables were investigated: stimulus intensity,
      stimulus viscosity, mouth movements, and presentation method. During the initial
      seconds of stimulation, adaptation to the weakest of the two solutions was
      faster. Although more viscous stimuli were less sweet, viscosity as such did not
      affect adaptation rate, nor did mouth movements. Among the three presentation
      methods, a sucrose-soaked filter paper on the tongue produced more adaptation
      than either sipping the solution or flowing it over the tongue. This suggests
      that even mouth movements far more subtle than those still present in the no
      movement condition of a sip-and-spit experiment can disrupt the adaptation
      process.

PMID- 10909253
TI  - Effects of time intervals and tone durations on auditory stream segregation.
AB  - Adult listeners rated the difficulty of hearing a single coherent stream in a
      sequence of high (H) and low (L) tones that alternated in a repetitive galloping
      pattern (HLH-HLH-HLH...). They could hear the gallop when the sequence was
      perceived as a single stream, but when it segregated into two substreams, they
      heard H-H- ... in one stream and L-L- ... in the other. The onset-to-onset time
      of the tones, their duration, the interstimulus interval (ISI) between tones of
      the same frequency, and the frequency separation between H and L tones were
      varied. Subjects' ratings on a 7-point scale showed that the well-known effect of
      speed's increasing stream segregation is primarily due to its effect on the ISI
      between tones in the same frequency region. This has implications for several
      theories of streaming.

PMID- 10909252
TI  - Phonetic priming, neighborhood activation, and PARSYN.
AB  - Perceptual identification of spoken words in noise is less accurate when the
      target words are preceded by spoken phonetically related primes (Goldinger, Luce,
      & Pisoni, 1989). The present investigation replicated and extended this finding.
      Subjects shadowed target words presented in the clear that were preceded by
      phonetically related or unrelated primes. In addition, primes were either higher
      or lower in frequency than the target words. Shadowing latencies were
      significantly longer for target words preceded by phonetically related primes,
      but only when the prime-target interstimulus interval was short (50 vs. 500
      msec). These results demonstrate that phonetic priming does not depend on target
      degradation and that it affects processing time. We further demonstrated that
      PARSYN--a connectionist instantiation of the neighborhood activation model-
      accurately simulates the observed pattern of priming.

PMID- 10909254
TI  - The perception of waning signals: decruitment in loudness and perceived size.
AB  - When a tone or broad-band noise sweeps smoothly from a moderate intensity to a
      low one, the loudness at the end of the sweep is far less than what would be
      predicted from its intensity. The accelerated reduction in loudness, which was
      first reported by Canevet (1986) and confirmed in several later reports, has been
      called loudness decruitment, and has been tentatively interpreted as the result
      of some form of adaptation. Since both simple and induced adaptation have
      distinctive temporal profiles, we undertook a series of studies in which we
      varied the duration of a tone whose intensity was continuously changing, to see
      whether the effect of duration on decruitment resembled the effects of duration
      on adaptation. We discovered that the magnitude of decruitment remained
      unaffected when the duration of the sweep was reduced far below the durations of
      90 to 180 sec that have been used in previous studies. The same effect was
      observed for durations of around 20 sec, but it declined rapidly to a low level
      at the lowest duration of 1.0 sec. This temporal pattern is strikingly different
      from what has been reported for either simple or ipsilaterally induced
      adaptation, which suggests that neither form of adaptation can account for the
      entire effect. We also wanted to know whether an analogous phenomenon could exist
      for a sensory modality other than hearing. In the present study, observers were
      asked to judge the apparent size of a solid disk on a computer monitor, the disk
      increased or decreased continuously in area, or appeared as a series of separate
      areas, either in random order or in ordered progressions. We found that, as in
      the case of loudness, apparent size decreased more rapidly when the areas
      decreased continuously than would have been predicted from the actual areas
      themselves. We also found that some part of the accelerated shrinkage was due to
      a response bias in the observers' judgments that stemmed from knowledge that
      every value in a continuously changing series is predictably smaller (or larger,
      for a growing series). Whether the remaining part of the effect is a sensory
      phenomenon is an important issue for future research.

PMID- 10909255
TI  - Tones disappear faster in the right ear than in the left.
AB  - In order to gain further information on the characteristics and physiological
      correlates of tone decay in humans, the tone decay test was administered to 58
      normal-hearing subjects, successively in the left and right ears and in absence
      and presence of a contralateral noise. The results revealed that tone decay was
      greater in the right than in the left ear and was increased by contralateral
      noise. The contralateral effect of this noise on cochlear biomechanisms was then
      estimated by measuring contralaterally induced variations in the amplitude of
      click-evoked otoacoustic emissions in the same subjects. In the right ear, the
      increase in tone decay and the decrease in otoacoustic emission amplitude--both
      induced by contralateral noise--were positively correlated (r = .315, p = .016).
      Furthermore, the contralateral changes in otoacoustic emission amplitude were
      found to be on average larger in the right than in the left ear, this asymmetry
      being correlated with that observed for the tone decay. These findings are
      discussed in relation to previous results on simple and induced loudness
      adaptation in the vicinity of threshold, on contralateral attenuation of
      otoacoustic emissions and on the influence of the auditory efferents on cochlear
      biomechanisms.

PMID- 10909256
TI  - Induction of quinone reductase and glutathione transferase in rat tissues by
      juglone and plumbagin.
AB  - The ability of the naturally-occurring naphthoquinone derivatives, juglone and
      plumbagin, to increase tissue activities of the Phase II detoxification enzymes
      quinone reductase (QR) and glutathione transferase (GT) has been investigated in
      rats. Groups of female Sprague-Dawley rats were dosed by oral intubation on 5
      consecutive days with either juglone or plumbagin at 12.5, 25, 50, 75, 100 or 125
      mumoles/kg/day. The animals were then killed and the activities of QR and GT
      determined in tissue homogenates. The naphthoquinone derivatives had no
      significant effect on enzyme activities in the liver, spleen, heart, lung or
      urinary bladder. Increases in the activities of one or both enzymes were
      recorded, however, in the caecum, kidney, forestomach, duodenum, colon, glandular
      stomach and jejunum. The possibility that induction of Phase II enzymes could
      contribute to the previously-reported ability of juglone and plumbagin to protect
      animals against chemically-induced intestinal neoplasia is discussed.

PMID- 10909257
TI  - Cytotoxic neolignans from the stem wood of Machilus obovatifolia.
AB  - Four new cytotoxic neolignans, machilusol A (1), machilusol C (3), machilusol D
      (4), machilusol E (5) as well as two new inactive neolignans, machilusol B (2)
      and machilusol F (6), were isolated from the stem wood of Machilus obovatifolia.
      All structures were identified by means of spectroscopic analysis.

PMID- 10909258
TI  - Relaxant and antispasmodic actions of methyleugenol on guinea-pig isolated ileum.
AB  - The effects of methyleugenol (ME) on guinea-pig isolated ileum were studied. ME
      reversibly relaxed basal tonus (EC50 of 52.2 +/- 18.3 microM), an action
      unaltered by 0.5 microM tetrodotoxin or 0.5 mM hexamethonium, and relaxed the
      ileum pre-contracted with 60 mM KCl. ME slightly hyperpolarized the ileum from 
      57.3 to -62.8 mV but had no effect in depolarised tissues. ME inhibited
      contractions induced by ACh, histamine and KCl with IC50 values of approximately
      82, 124, and 65 microM, respectively. Our results suggest that ME induces
      relaxation of guinea-pig ileum by a direct action on smooth muscle via a
      mechanism largely independent of alterations of membrane potential (Em).

PMID- 10909259
TI  - Modulatory role of ginsenosides injected intrathecally or
      intracerebroventricularly in the production of antinociception induced by kappa
      opioid receptor agonist administered intracerebroventricularly in the mouse.
AB  - We examined the effects of ginseng total saponin and several ginsenosides
      injected intrathecally (i.t.) or intracerebroventricularly (i.c.v.) on the
      antinociception induced by U50, 488H (trans-3,4-dichloro-N-methyl-N-[2- (1
      pyrrolidinyl)cyclohexyl]benzeocetamide; a kappa opioid receptor agonist)
      administered i.c.v. The tail-flick test was used as an analgesic assay. Total
      saponin fraction at doses of 0.1 to 20 micrograms, which when administered
      intrathecally (i.t.) or intracerebroventricularly (i.c.v.) alone did not affect
      the latencies of tail-flick threshold, attenuated dose-dependently the inhibition
      of the tail-flick response induced by U50, 488H (60 micrograms) administered
      i.c.v. The duration of antagonistic action of total saponin fraction against U50,
      488H-induced antinociception lasted at least for 6 h. Various doses (from 0.1 to
      1 microgram) of ginsenosides Rb1, Rb2, Rc, Rd, and Rg1, but not Re, injected i.t.
      dose-dependently attenuated antinociception induced by U50, 488H administered
      i.c.v. Furthermore, various doses (from 1 to 10 micrograms) of ginsenosides Rb2
      and Re, but not Rb1, Rc, Rd, and Rg1, injected i.c.v. dose-dependently attenuated
      antinociception induced by U50, 488H administered i.c.v. In summary, ginsenosides
      Rb1, Rb2, Rc, Rd, and Rg1 administered spinally appear to be responsible for
      blocking the antinociception induced by U50, 488H administered supraspinally,
      whereas ginsenosides Rb2 and Re administered supraspinally appear to be
      responsible for blocking the antinociception induced by U50, 488H administered
      supraspinally.

PMID- 10909260
TI  - Insulinotropic effect of Citrullus colocynthis fruit extracts.
AB  - Infusions of Citrullus colocynthis Schrad. (Cucurbitaceae) fruits are
      traditionally used as antidiabetic medication in Mediterranean countries, but to
      our knowledge no studies have been undertaken so far to determine the possible
      mechanisms involved in the antidiabetic properties of the fruit. The present
      study was designed to investigate whether these fruits possess insulinotropic
      effects. For this purpose, different extracts of Citrullus colocynthis seed
      components were obtained: RN II (crude extract), RN VI (hydro-alcoholic extract),
      RN X (purified extract) and RN XVII (beta-pyrazol-1-ylalanine), the major free
      amino acid present in the seeds. The insulin secretory effects of these different
      extracts were evaluated in vitro in the isolated rat pancreas and isolated rat
      islets in the presence of 8.3 mM glucose. All tested extracts, when perfused for
      20 min at 0.1 mg/ml, immediately and significantly stimulated insulin secretion.
      This effect was transient. In addition, the purified extract (RN X) provoked a
      clear dose-dependent increase in insulin release from isolated islets. Moreover,
      a significant and persistant increase in pancreatic flow rate appeared during RN
      VI, RN X and RN XVII perfusions. In conclusion, our results show that different
      Citrullus colocynthis seed extracts have an insulinotropic effect which could at
      least partially account for the antidiabetic activities of these fruits.

PMID- 10909262
TI  - Influence of curcumin on cyclosporin-induced reduction of biliary bilirubin and
      cholesterol excretion and on biliary excretion of cyclosporin and its
      metabolites.
AB  - We investigated the ability of curcumin, which can be extracted from different
      Curcuma species, to prevent cyclosporin-induced reduction of biliary bilirubin
      and cholesterol excretion, and its influence on biliary excretion of cyclosporin
      (CS) and its metabolites in the bile fistula model in rats. I.v. injection of
      curcumin (25 and 50 mg/kg) after 30 min increased dose-dependently basal bile
      flow (30 microliters/kg/min) up to 200%, biliary bilirubin excretion (3000
      pmol/kg/min) up to 150%, and biliary cholesterol excretion (22 nmol/kg/min) up to
      113%. CS (30 mg/kg) reduced bile flow to 66% and biliary excretion of bilirubin
      and of cholesterol to 33% of the basal value 30 min after i.v. injection. I.v.
      administration of curcumin (25 and 50 mg/kg) 30 min after CS increased bile flow
      dose dependently again to 130% for 1 hour and biliary excretion of cholesterol
      and of bilirubin to 100% of the basal value for 30 and 150 min, respectively.
      Injection of curcumin 15 min before CS prevented the CS-induced drop of bile flow
      at 50 mg/kg and reduction of biliary bilirubin excretion already at 25 mg/kg
      until the end of the experiment (180 min). The CS-induced reduction of biliary
      cholesterol excretion, however, was not prevented by curcumin. Finally, the
      biliary excretions of CS (1200 ng/kg/min) and its metabolites (1200 ng/kg/min)
      were slightly reduced by curcumin at a dose of 50 mg/kg (to 83% of the initial
      values). The clinical importance of these controversial effects remains to be
      shown.

PMID- 10909261
TI  - Inhibition of the lethal and myotoxic activities of Crotalus durissus terrificus
      venom by Tabernaemontana catharinensis: identification of one of the active
      components.
AB  - In Brazilian folk medicine, victims of bites by poisonous animals are usually
      treated with plant extracts derived from the diverse national flora. The chemical
      and pharmacological properties of most extracts were yet not investigated. In the
      rural community of Assis-SP, the root bark of Tabernaemontana catharinensis
      ("leiteiro", "cow milk") is applied to the site of the snake bite and believed to
      neutralize the effect of the venom. We report here the ability of the lyophilized
      aqueous extract (AE) and of a pure compound obtained from the ethanolic extract
      of T. catharinensis to inhibit the lethal and myotoxic activities of C. d.
      terrificus (South American rattlesnake) venom. Doses of 10 mg AE/100 g, injected
      (i.m., rat) 20 s after injecting (i.m.) the venom and that of 2.5 mg AE/100 g,
      incubated for 1 h at 25 degrees C with the venom before injection (i.m.) were
      able to neutralize the lethal activity of 2LD50. These data indicate that T.
      catharinensis could be used as a source of a model molecule able to neutralize
      the lethality and myotoxicity induced by C. d. terrificus venom. Its ethanolic
      extract was then fractionated on a silica gel 60 chromatography column affording
      fractions A to F. Fraction A consisted basically of non-polar compounds, terpenes
      and sterols. Fraction D showed a pronounced antiophidian activity which was later
      correlated with the presence of the quaternary alkaloid 12-methoxy-4
      methylvoachalotine in this fraction. This alkaloid was isolated and inhibited
      100% lethality when injected 20 s after 2 LD50 at 1.7 mg/100 g.

PMID- 10909263
TI  - In vitro synergism between nyasol, an active compound isolated from Anemarrhena
      asphodeloides, and azole agents against Candida albicans.
AB  - The antifungal activity of nyasol (NYS) alone or with various antifungal agents
      was measured in vitro against Candida albicans, Aspergillus fumigatus, and
      Trichophyton mentagrophytes. NYS is a compound recently purified from a medicinal
      plant, Anemarrhena asphodeloides. Among 12 agents, miconazole (MCZ), ketoconazole
      (KCZ), clotrimazole (CTZ), and cerulenin showed marked synergistic effects
      against C. albicans. The fractional inhibition concentration (FIC) indices
      against 4 strains of C. albicans were 0.067-0.31 for MCZ plus NYS, 0.078-0.31 for
      KCZ plus NYS, and 0.098-0.13 for CTZ plus NYS. These values indicate the
      possibility of using NYS as an adjuvant to azole agents in the chemotherapy of
      candidiasis.

PMID- 10909264
TI  - Effect of honey on naringin absorption from a decoction of the pericarps of
      Citrus grandis.
AB  - To measure naringin/naringenin absorption of a decoction prepared from the
      pericarps of Citrus grandis and to investigate the effect of honey on
      naringin/naringenin absorption, six healthy males received 200 mL decoctions of
      untreated and honey-treated Pericarpium Citri Grandis in a randomized crossover
      design. The absorption was measured by renal recovery of naringenin
      glucuronides/sulfates over 48 hours. The contents of naringin/naringenin in 200
      mL decoctions of untreated and honey-treated Pericarpium Citri Grandis were
      determined to be 261.5/23.8 mumol and 303.3/11.6 mumol, respectively. The mean
      cumulated renal excretion of naringenin glucuronides/sulfates after intake of
      these two decoctions were 74.8 mumol (26.2% of dose) and 49.8 mumol (15.8% of
      dose), respectively. Paired Student's t-test showed that the difference of the
      total renal recovery of naringin/naringenin between the two decoctions was
      significant. The results indicated that honey significantly reduced
      naringin/naringenin absorption by 33.4% in humans and suggested that honey
      treatment might alter the efficacy of Pericarpium Citri Grandis.

PMID- 10909266
TI  - The regulation of solasodine production by Agrobacterium rhizogenes-transformed
      roots of Solanum aviculare.
AB  - Transgenic roots of Solanum spp. containing extra copies of an hmgr gene derived
      from Artemisia annua have been obtained via transformation with Agrobacterium
      rhizogenes. Hairy root clones of Solanum aviculare which were transgenic for hmgr
      typically grew faster than those which did not contain extra copies of this gene
      and also accumulated up to 4.2 times more solasodine when grown under dark, but
      not light, conditions. The implications of these findings with respect to the
      regulation of solasodine production in Solanum spp. are considered.

PMID- 10909265
TI  - Oral absorption and bioavailability of tea catechins.
AB  - The absorption characteristics and oral bioavailability of three tea catechins,
      namely (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), and (-)
      epigallocatechin gallate (EGCG), were assessed in this study. Male Sprague Dawley
      rats (210-230 g) received either an intravenous (i.v. 50 mg/kg) or oral (5000
      mg/kg) dose of decaffeinated catechin-fraction containing EC (5%), EGCG (50%),
      and ECG (13%). Concentrations of the compounds in plasma, urine, and feces were
      measured using HPLC. A non-compartmental approach was employed for
      pharmacokinetic analysis. Results indicated that maximum plasma concentrations
      for the catechins (15-112 micrograms/ml) were achieved at 2 h post-oral dosing
      and the apparent volume of distribution (Vd/F) ranged from 30 to 63 l/kg.
      Absolute bioavailability (F) of EC, EGCG, and ECG was assessed to be 0.39, 0.14,
      and 0.06, respectively. Estimates of terminal elimination half-life (t1/2, lambda
      z) of the catechins after oral dosing were 451-479 min and were 1.4-10 fold
      longer than those observed for the i.v. dosing. The discrepancy in terminal
      elimination and low rate and extent of absorption indicated the possibility of
      flip-flop kinetics. Respective urinary recoveries were 0.17-4.72% and 2.11-14.2%
      after oral and i.v. dosing. In conclusion, the low systemic availability of tea
      catechins observed could be a result of slow absorption, high first pass effect,
      and wide tissue distribution.

PMID- 10909267
TI  - Production of amarogentin in root cultures of Swertia chirata.
AB  - Conventional and Agrobacterium rhizogenes-transformed root cultures were studied
      with respect to growth and amarogentin content following cultivation in various
      growth media. The fastest growth rate was observed using Nitsch medium. The best
      amarogentin content was obtained after cultivation in root culture (RC) medium
      for which the slowest growth rate was noticed. Addition of sucrose at 6% and 9%
      (w/v), respectively, also resulted in better growth rates and increased total but
      unaltered relative amarogentin content compared to 3% (w/v) sucrose. No change in
      amarogentin content was observed upon addition of elicitors, putative precursors
      of amarogentin biosynthesis, and plant growth hormones with the exception of
      salicylic acid and chitosan: at 100 mM salicylic acid a reduction and at 25 mg/L
      chitosan an increase of amarogentin were observed at significant levels. The
      cultivation of S. chirata roots in a 2-L stirred-tank bioreactor was successful
      only with a stainless-steel mesh fitted inside the culture vessel for
      immobilization of the roots. A 15-fold enhancement of amarogentin content in the
      medium was achieved by a root permeabilisation treatment using Tween 20 at 1.3%
      (v/v) final concentration in the bioreactor.

PMID- 10909268
TI  - Antibacterial diterpenes from the roots of Salvia viridis.
AB  - Three new diterpenes, salviviridinol, viridinol, viridone, five known diterpenes,
      sugiol, 1-oxoferruginol, ferruginol, aethiopinone and microstegiol, abietane and
      rearranged abietane diterpenes were isolated from the roots of Salvia viridis.
      These compounds were assayed against S. aureus ATCC 6538 P, E. coli ATCC 8739, P.
      mirabilis ATCC 14153, K. pneumonia ATCC 4352, P. aeruginosa ATCC 27853, S.
      epidermidis ATCC 12228, E. faecalis ATCC 29212 and a yeast C. albicans ATCC
      10231. 1-Oxoferruginol showed activity against B. subtilis, S. aureus, S.
      epidermidis and a modest activity against P. mirabilis, migrostegiol had a little
      activity against B. subtilis. The structures of the compounds were established by
      1D and 2D NMR spectroscopic techniques.

PMID- 10909269
TI  - Bioactive compounds from Celaenodendron mexicanum.
AB  - Bioactivity-directed fractionation of the CHCl3-MeOH extract of the leaves of
      Celaenodendron mexicanum by means of the brine shrimp lethality test and
      chromatographic techniques led to the isolation of three carboxylic acid
      triterpenes, the new tirucalla-type triterpene, 3 alpha-hydroxytirucalla-7,24Z
      dien-26-oic acid, 3-oxotirucalla-7,24Z-dien-26-oic acid, and epi-oleanolic acid,
      and three biflavonoids amentoflavone, podocarpusflavone A, and podocarpusflavone
      B. Four non-active compounds friedelin, maytensifolin B, 3 beta-hydroxyfriedelan
      16-one, and celaenodendrolide were also obtained. epi-Oleanolic acid was the most
      active against brine shrimps with LC50 value of 23.3 microM. In addition, all
      isolates were tested for in vitro antiprotozoal and cytotoxic activities. 3
      Oxotirucalla-7,24Z-dien-26-oic acid and epi-oleanolic acid showed the highest
      activity against Leishmania donovani promastigotes with IC50 values of 13.7 and
      18.8 microM, respectively. Only 3-oxotirucalla-7,24Z-dien-26-oic acid showed
      activity against Trypanosoma brucei brucei bloodstream forms with IC50 value of
      16.8 microM.

PMID- 10909270
TI  - Inhibitors of nitric oxide synthesis and TNF-alpha expression from Magnolia
      obovata in activated macrophages.
AB  - Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) are the major
      mediators produced in activated macrophages which contribute to the circulatory
      failure associated with septic shock. An activity-guided fractionation of an MeOH
      extract of stem bark of Magnolia obovata afforded two inhibitors of NO production
      in lipopolysaccharides (LPS)-activated macrophages by the suppression of i-NOS
      expression. Their structures were elucidated by spectroscopic methods to be
      magnolol and honokiol with IC50 values of 16.8 and 6.4 microM, respectively. They
      also inhibited the production of TNF-alpha in LPS-activated macrophages. Thus,
      these compounds may be possible candidates for the development of new drugs to
      treat endotoxemia accompanied by the overproduction of NO and TNF-alpha.

PMID- 10909271
TI  - Isolation of (S)-(+)-naproxene from Musa acuminata. Inhibitory effect of
      naproxene and its 7-methoxy isomer on constitutive COX-1 and inducible COX-2.
AB  - The isolation and characterisation of (S)-(+)-6-methoxy-alpha-methyl-2
      naphthaleneacetic acid, a well known synthetic non-steroidal anti-inflammatory
      drug (naproxene), from a natural source is described for the first time. We
      evaluated the ability of naproxene and its 7-methoxy isomer to abrogate
      constitutive COX-1 and inducible COX-2 activity in human A549 cells. Naproxene
      inhibited COX-1 (IC50 = 3.42 microM) and COX-2 (IC50 = 1.53 microM), whereas the
      7-methoxy isomer had no appreciable effect on COX-1 (IC50 >> 100 microM) but also
      abrogated the activity of COX-2 enzyme (IC50 = 14.42 microM).

PMID- 10909272
TI  - Antiplasmodial compounds from the wood-decayed fungus Xylaria sp. BCC 1067.
AB  - Bioassay-guided fractionation of the extract from the wood-decayed fungus Xylaria
      sp. BCC 1067 led to the isolation of five antiplasmodial compounds, (-)
      depudecin, (+)-phaseolinone, (+)-phomenone, 19,20-epoxycytochalasin Q, and (E)
      methyl 3-(4-methoxyphenoxy)propenoate. These structures were elucidated using
      spectroscopic methods, especially NMR analysis.

PMID- 10909273
TI  - Achyrocline satureioides essential oils from southern Brazil and Uruguay.
AB  - The essential oils of the aerial parts of Achyrocline satureioides (D.C.) Lam., a
      regional medicinal plant, from different collection locations in the South of
      Brazil and Uruguay were examined by GC and GC-MS. Monoterpene and sesquiterpene
      hydrocarbons were the main fractions of both the oils from Brazil and Uruguay.
      The oxygenated monoterpenes and sequiterpenes were at much lower percentage in
      both samples. The Uruguayan samples have 1,8-cineole which is not present in the
      Brazilian samples and has not been reported in other samples from Brazil. The
      results indicated a high biodiversity of the native populations of A.
      satureioides.

PMID- 10909274
TI  - Oxoaporphine alkaloids and quinones from Stephania dinklagei and evaluation of
      their antiprotozoal activities.
AB  - Bioactivity-guided fractionation of Stephania dinklagei yielded six compounds
      including, two zwitterionic oxoaporphine alkaloids, N-methylliriodendronine, and
      2-O,N-dimethylliriodendronine, two oxoaporphine alkaloids, liriodenine, and
      dicentrinone, one aporphine alkaloid, corydine, and one anthraquinone, aloe
      emodin. Apart from corydine, the isolates have not been reported as constituents
      of S. dinklagei. N-Methylliriodendronine, and 2-O,N-dimethylliriodendronine are
      reported for the first time as natural products. All isolated compound were
      tested for antiprotozoal activity and cytotoxic activities in vitro. N
      Methylliriodendronine was the most active against L. donovani amastigotes (IC50 =
      36.1 microM). Liriodenine showed the highest activity against Leishmania
      donovani, and Plasmodium falciparum with IC50 values of 26.16 and 15 microM,
      respectively. Aloe-emodin was the only compound active (IC50 = 14 microM) against
      T. b. brucei.

PMID- 10909275
TI  - A new steroidal alkaloid from the roots of Cynanchum caudatum.
AB  - A new steroidal alkaloid, 12-O-nicotinoylsarcostin, gagamine (1), was isolated
      from the roots of Cynanchum caudatum Max. (Asclepiadaceae), together with a known
      alkaloid, gagaminine (2). Their structures were established using spectroscopic
      methods, some 13C-NMR data of 2 have to be revised.

PMID- 10909276
TI  - Cytotoxic triterpene acids from the Peruvian medicinal plant Polylepis racemosa.
AB  - Cytotoxicity-guided fractionation of the bark and stem extract of Polylepis
      racemosa led to the identification of ursolic acid, pomolic acid, 3-O
      acetylpomolic acid, and 2-oxopomolic acid. Pomolic acid was the most cytotoxic
      component, and was specific for M-14 melanoma and ME180 cervical carcinoma, with
      GI50 values of 6.9 and 8.3 micrograms/mL respectively.

PMID- 10909277
TI  - Cytotoxic triterpenes from stem bark of Physocarpus intermedius.
AB  - Seven triterpenes (1-7), i.e., betulinic acid 1, ursolic acid 2, oleanolic acid
      3, 3-O-caffeoyloleanolic acid 4, euscaphic acid 5, 2 alpha-hydroxyursolic acid 6
      and maslinic acid 7 were isolated from the stem bark extract of P. intermedius as
      active principles responsible for the cytotoxicity against five cultured human
      tumor cell lines, i.e., A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2
      (melanoma), XF498 (central nerve system) and HCT-15 (colon), in vitro.

PMID- 10909278
TI  - Two new acyclic diterpene-gamma-lactones from Salix matsudan.
AB  - Two new phytane-type diterpene-gamma-lactones named hanliuine I (1) and hanliuine
      II (2), were isolated from leaves of Salix matsudana (chinese name "hanliu",
      Berberidaceae). Their structures were deduced from 1D and 2D NMR techniques.

PMID- 10909279
TI  - Betulenols from Betula species.
AB  - The essential oils from buds of five Betula species growing in Turkey were
      investigated by GC-MS. A major component in the essential oils was shown to be 14
      hydroxy-beta-caryophyllene (6). The structure of beta-betulenal (12) which was
      isolated from Betula essential oils was also confirmed by synthesis. Chemical
      reactions yielded 14-acetoxy-beta-caryophyllene (15), 14-hydroxy-isocaryophyllene
      (10) and its acetate (14), giving evidence to the natural occurrence in Betula
      species of the formerly known alpha-betulenol acetate (3), beta-betulenol (2) and
      beta-betulenol acetate (4), respectively. Compounds 6, 9, 10, 12, and 15 were
      evaluated for antimicrobial activity.

PMID- 10909280
TI  - Cytotoxic components from the bark of Stauranthus perforatus from Monteverde,
      Costa Rica.

PMID- 10909281
TI  - [Operative outcome in children with total anomalous pulmonary venous connection].
AB  - The authors present their experience in surgical treatment of children with total
      anomalous pulmonary venous connection. A retrospective analysis was carried out
      in 42 patients operated on in the years 1979-1999. The group included 30 boys
      aged 7 days to 7 years (mean 170 +/- 480 days) and 12 girls aged 14 days to 7
      months (mean 86 +/- 80 days). Diagnostic studies allowed to determine that 24
      patients (57%) had supracardiac type (type I), nine (21%)--cardiac (type II),
      five (12%)--infracardiac (type III) and four (10%)--mixed (type IV). The
      diagnosis was based on clinical examinations and echocardiography, supplemented
      in 17 patients (40%) by hemodynamic studies and angiocardiography. Preoperative
      pulmonary hypertension was noted in 34 children (81%), including 15 patients
      (36%) diagnosed by hemodynamic studies and 19 children (45%) by echocardiography.
      All children were operated on in deep hypothermia with circulatory arrest. In the
      early postoperative period (30 days), seven children (17%) died, while four more
      (9.5%) died in the latter period. The former were characterized by significantly
      lower birth weight values (p = 0.023). The total mortality rate was higher in
      children with type II and III anomalies. No statistically significant association
      was found between preoperative pulmonary hypertension and early mortality. Thirty
      one children (74%) remain in late follow-up. All of them are in NYHA (New York
      Heart Association) class I and develop normally. Total anomalous pulmonary venous
      connection is a rare congenital anomaly that can be fully repaired with improving
      early and late results.

PMID- 10909282
TI  - [IA-2 and anti-GAD antibodies in patients with newly diagnosed type 1 diabetes
      and their first degree relatives].
AB  - Antibodies recognising different pancreatic autoantigens (Abs) are detected many
      years before the clinical onset of insulin-dependent diabetes mellitus (IDDM).
      The humoral immune alterations, observed in the susceptible subjects, for example
      in first degree relatives of IDDM patients, could serve as predictive markers of
      IDDM development. It has recently been suggested that the predictive value of
      these humoral markers is associated with the number of the studied antibodies
      directed against different pancreatic antigens (ICA, GADA, IA-2,A IAA). The aim
      of the study was the estimation of the prevalence and titre of the antibodies
      directed against protein tyrosine phosphatase-2 (IA-2) and glutamic acid
      decarboxylase (GAD) in patients with newly diagnosed diabetes type 1 and their
      first degree relatives. The investigations were carried out in 52 diabetics (aged
      5-25 years) and 136 first degree relatives. IA-2A and GADA were performed by
      radiobinding assay (RIA) using 2 microliters of serum and recombinant S35
      labelled GAD65 and IA-2 antigens. The threshold of Abs detection was > or = 97.5
      centile (of healthy schoolchildren). At least one of the antibody marker was
      detected in 92.7% of newly diagnosed IDDM patients, slightly more frequently
      observed were GADA (78.8%) than IA-2A (71.2%). The presence of 2 types of
      antibodies was found in 8.7% of parents and 9.4% of the siblings. The results of
      our study confirm high sensitivity and specificity of the combined measurement of
      IA-2A and GADA in recognising of autoimmune alterations in diabetes type 1
      development. Taking into consideration small volume of the serum suitable for Abs
      measurement and possibility of the combined estimation of these Abs it seems that
      IA-2A and GADA combined measurement could actually serve as a screening marker
      for the detection of high risk of IDDM subjects also in the Polish population,
      but studies concerning their predictive value in the general population are
      suggested.

PMID- 10909283
TI  - [Antibodies against Borrelia garinii in diagnosis of Lyme disease].
AB  - Prevalence of antibodies against Borrelia garinii (Bg) was analysed in sera of 42
      patients with Lyme borreliosis confirmed through demonstration of antibodies
      against antigen 41 kDa of Borrelia burgdorferi sensu stricto (Bbss). IgM or IgG
      antibodies against Bg were found in sera of 88% patients. Agreement of the
      results between Bg and Bbss tests related to IgM antibodies reached 84% and to
      IgG antibodies 76%. Comparison of individual results revealed significant
      positive correlation of optical densities in respect to both IgM and IgG
      antibodies. These results indicate possible use of detection of anti-Borrelia
      garinii antibodies in diagnostics of Lyme borreliosis in Poland.

PMID- 10909284
TI  - [Point scale quantification of changes in computed tomography of chronic
      hyperplastic rhinosinusitis].
AB  - Coronal CT scans have dramatically improved imaging of the nasal cavity and
      paranasal sinuses. However, quantification of the extent of chronic sinusitis is
      not possible by simple reviewing of the CT images. The aim of the study was to
      introduce a CT scoring scale to assess the extend of sinusal pathology. Seventeen
      patients with clinically recognized aspirin-sensitive rhinosinusitis asthma
      syndrome (aspirin triad) were studied. The CT scans were reviewed and scored for
      extent of the disease by two independent radiologists. Repeated readings of the
      scans showed close correlation between the two assessments. The authors conclude,
      that CT scoring system for quantitation of the disease extent is reproducible and
      may be useful in clinical practice.

PMID- 10909285
TI  - [Intradural reconstructive surgery of anterior fossa dural lesions using
      pedunculated periosteal flaps].
AB  - The cranio-cerebral injury could result in cerebro-spinal fluid fistula with
      serious consequences in form of meningitis. In a number of cases a surgical
      procedure is needed, however in spite of established standards the controversies
      are still present concerning approach and reconstruction technique. The author
      presents his own experience in duroplastic operations with intradural use of
      pedunculated periostal allograft flaps.

PMID- 10909286
TI  - [Diagnosis, treatment and prognosis in cases of renal clear cell carcinoma
      metastases into the thyroid gland].
AB  - The most common metastatic tumour of the thyroid gland which is clinically
      revealed is renal clear cell carcinoma (RCCC). Our clinical experience in cases
      of RCCC metastases into thyroid gland is reviewed in terms of the history of the
      disease, obligatory diagnostic procedures, surgical management and outcome
      prognosis. We believe that all the patients with even a remote RCCC history
      require systematic follow-up including thyroid gland as metachronic metastatic
      disease can occur many years after primary surgery. Clinical diagnosis and
      ultrasound of the thyroid gland is essential in selection for surgical treatment.
      Confirmation of malignancy in FNA (fine needle aspiration) in often difficult
      regarding concomitant multinodular goitre. Enlargement of a single thyroid nodule
      except L-thyroxin therapy for 3-6 months is a sufficient indication for surgical
      treatment, not depending on FNA result, particularly when a suspected nodule
      becomes bigger than 30 mm in diameter.

PMID- 10909287
TI  - [HIV nephropathy and other kidney diseases in patients with human
      immunodeficiency virus infections].
AB  - Kidney diseases are a quite frequent complication of HIV infection. They may be
      caused by HIV infection itself, secondary infections or administered drugs. The
      most often causes of acute renal failure and main glomerular diseases in this
      group of patients are discussed. Special attention was paid to HIV associated
      nephropathy as a specific disease for the HIV infection. Epidemiology, clinical
      presentation, histological changes, pathogenesis and treatment options are
      presented.

PMID- 10909288
TI  - [Parathyroid neoplasm--diagnostic challenge and therapeutic difficulty].
AB  - The paper presents current diagnostic and therapeutic approach in parathyroid
      cancer. The suspicion of parathyroid cancer should be taken into account in
      patients with primary hyperparathyroidism symptoms (and elevated total and
      ionised calcium blood level and PTH blood level), present palpable cervical mass
      and enlarged cervical lymph nodes. Further diagnosis should be based on
      ultrasound of the neck (including power-Doppler ultrasound), subtraction 99mTc
      MIBI and 123J scintigraphy, ultrasound-guided fine needle aspiration, and CT or
      MRI if necessary to assess the stage of the process. The elective surgical
      procedure should be primary 'en block' excision of the tumour with the unilateral
      thyroid lobe and the following loco-regional adjuvant radiotherapy. Patients who
      underwent surgical treatment due to parathyroid cancer require long-term follow
      up as the risk of local recurrence or distant metastases (mostly into lungs or
      bones) remains high even many years after initial operation. Patients with
      dissemination usually suffer from severe hypercalcemia leading to death if
      untreated correctly. Thus, so crucial is effective treatment of hypercalcemia
      (diuresis, biphosphonates, calcitonine, oktreotide).

PMID- 10909289
TI  - [Nutritional therapy in stable liver cirrhosis].
AB  - Clinical and biochemical signs of protein-calorie malnutrition are associated
      with every liver disease. Malnutrition increases the number of complications and
      makes patient's prognosis worse. Early started specific treatment including
      nutritional support is an important medical strategy to limit malnutrition and to
      maintain liver functions. The author presents principles of nutritional treatment
      in stable liver cirrhosis.

PMID- 10909290
TI  - [Analysis of selected methods for intrauterine stimulation of fetal pulmonary
      maturation].
AB  - Preterm delivery is still a major cause of infant morbidity and mortality.
      Premature infants develop numerous complications including respiratory distress
      syndrome, intraventricular hemorrhage, patent ductus arteriosus, necrotising
      enterocolitis, etc. Respiratory distress syndrome is the leading problem in
      perinatology. The incidence of RDS accounts for 70% of all infants delivered
      before 30 week's gestation and about 20% neonates born between 32-37 week of
      pregnancy. Our paper presents current opinions and is a critical review of
      relevant literature on antenatal treatment before anticipated preterm deliveries.
      Recently performed meta-analysis prove that glucocorticoid therapy is effective
      in reducing aforementioned pathologies of prematurity. After brief account on
      effects of several hormones on fetal pulmonary maturity some beneficial
      interactions for enhanced fetal maturity are pointed out. Glucocorticoid
      mechanism of action in target cells and its biochemical implications are
      reviewed. The use of antenatal corticoids for fetal maturation and possible
      adverse maternal effects follow. Finally both short-term and long-term benefits
      of ANS are discussed. Thus there are convincing data to support the use of ANS in
      fetal pulmonary maturation. The current findings suggest that the improvement of
      respiratory outcome may depend on enhanced expression of phospholipids and
      proteins of the surfactant system and enzymes of antioxidant systems. We believe
      that use of antenatal corticosteroids for fetal maturation results in improvement
      of neonatal outcome and yields substantial savings in health care costs.

PMID- 10909292
TI  - [Gas gangrene or inflammation of the neck--diagnostic difficulties].
AB  - The authors describe a patient with an extensive inflammation of the neck soft
      tissues as a complication of the peritonsillar abscess. Follow-up computed
      tomography revealed gasi-form follicles in the inflammed neck soft tissues,
      suggesting gas gangrene. We report disseminate ways of the inflammation process
      on the financial tonsil, reasons of the gangrene also the infections of soft
      tissues caused by anaerobic bacteries--Clostridium. CT--examination in
      inflammatory tumors of the neck is valuable, permits to exclude expansion
      process, but it cannot give unequivocal answer to differentiate gas gangrene and
      phlegmon.

PMID- 10909291
TI  - [Intradural clivus chordoma: surgical treatment with no tumor regrowth 12 years
      after surgery].
AB  - We present a case of a 19-year-old woman treated in the Neurosurgery Department
      of Collegium Medicum of the Jagiellonian University in Krakow because of the
      clival chordoma. The patient with one year anamnesis, treated surgically and then
      rehabilitated, was examined 12 years after she left our department.
      Radiologically we did not find tumor regrowth. We only found diplopia, but this
      sign was present from the time of the operation. Such a long time of katamnesis
      proves possibility of total removal in this type of tumors.

PMID- 10909293
TI  - [Consultation and liaison psychosomatics: cui bono fuerit?].

PMID- 10909294
TI  - [Classical theme: "studies on pathogenesis" of Viktor von Weizsacker].

PMID- 10909295
TI  - [Aspects and convergences in the evolutionary theory of biological selection and
      the development of psychosomatic theory].
AB  - Psychotherapeutic theories have a lamarcistic trait in interpreting psychogeneous
      symptoms and signs. In the theory of Ch. Darwin the mechanism of selection plays
      an important role to interpret evolutionary processes. According to the
      psychotherapeutic process early infant relation-ships, the relation between
      description and structure, the six components of the affect and the convergence
      between non-verbal interaction and motivation are important.

PMID- 10909296
TI  - [Psychotherapeutic and psychosocial therapy in general practice. Results of
      demonstration project on quality management in psychosocial primary care].
AB  - Since 1987, psychosocial primary care (PPC) provided by General Practitioners,
      are reimbursed by German health insurances. The aim of the psychosocial primary
      care is to improve recognition and treatment of mental disorders in the primary
      care sector. As a part of a eight-center national demonstration program on
      quality management in the outpatient services, General Practitioners (n = 191)
      from 5 regions participated in the study. 1341 treatment episodes of patients
      with predominately psychosocial strain were documented. Differences between
      psychosocial strain, treatment and outcome were determined by analyses of
      variance. Men and patients beyond the age of 65 were underrepresented.
      Psychosocial treatments were offered more often to those patients, who had the
      highest level of anxiety and depression. Patients with physical illness, with
      pain and without psychological attribution to the illness belief were offered
      less psychosocial interventions and reached a worse outcome. The study outcome
      helps to improve training programs as to recognition and treatment of
      psychosocial problems in primary care. Male and generally elderly patients with
      somatic symptoms and lack of psychological attribution need a special
      psychosocial intervention to improve the outcome.

PMID- 10909297
TI  - [Consultation and liaison activity from the socioeconomic perspective. A plea for
      cost-benefit analysis in psychosomatics].
AB  - Within the last decade cost-effectiveness assumes a much more strategic
      perspective in the rationing of care that is taking place due to evidently
      increasingly limited financial resources and managed-care driven protocols. As
      universities and general hospitals face this increasing pressure to justify
      services within their facilities, consultation-liaison (C/L) programs need to
      carefully address and evaluate the financial base of the services they provide.
      Overlooking or neglecting the financial aspects of C/L-services has already
      resulted in the closure or service reduction of C/L-programs throughout the
      United States. Whereas a result of that development interest in cost
      effectiveness research is considerable in the US and GB and has produced some
      good evidence for the impact of psychosocial problems on the outcome and cost of
      medical care, nearly no such studies come from the German-speaking countries. The
      present article reviews the worldwide existing literature concerning cost
      effectiveness analyses of C/L-work and attempts to guide the reader through the
      currently available methods for cost-effectiveness research. As a conclusion we
      propose somatisation syndromes as one patient group. There the development of
      appropriate treatment regiments is vital both concerning clinical and
      socioeconomical aspects.

PMID- 10909298
TI  - [The psychology of compassion. An analysis of the 100th anniversary of the death
      of Fredrich Nietzsche].
AB  - Friedrich Nietzsche is supposed to have been one of the harshest critics of
      compassion. Many of his publications try to unmask its failings and to expose its
      true motives. From an ardent admirer of Schopenhauers's ethics of compassion,
      Nietzsche turned into a vigorous despiser of compassionate feelings. It is shown
      that this change was above all caused by overwhelming personal experiences of
      compassion due to illness and death in his family and, later on, with his first
      aid activities in military hospitals during the German-French war in 1870.
      Combined with that, Nietzsche suffered from feelings of passivity and
      helplessness, which gave him the impression of compassion being a negative and-
      in the end--loathed emotion.

PMID- 10909299
TI  - [Psychoosmology at the turn of the millennium: From "nasal reflex neurosis" to
      the modern psychosomatics of sudden anosmia].
AB  - This article offers a psychosomatic description of the medical disorder known as
      sudden anosmia, an illness which previously has been unjustly neglected. The
      authors present an operational definition of sudden anosmia and describe the
      illness's multi-facetted symptomatology. Sudden anosmia is influenced by a number
      of etiological factors. In this regard, it can be seen that not only classical
      medical factors such as neurophysiology and anatomy prove to be relevant, but
      also various characteristics of the fields of personality psychology, family
      psychology, and behavioral psychology as well. The modern diagnostics of sudden
      anosmia are conceived interdisciplinarily and span from olfactory measurements to
      rhino-psychological testing. The treatment of patients suffering from sudden
      anosmia is based on a multi-staged treatment concept. This concept equally
      considers both medical and psychological approaches, whereby behavior
      psychological treatment will be given particular importance in discussion of the
      latter. Processes for evaluation and quality assurance to monitor the methods of
      diagnostics and therapy provided for persons afflicted by sudden anosmia are
      still in their beginning stages.

PMID- 10909300
TI  - [Some general considerations and historical recollections regarding
      therapeutics].

PMID- 10909301
TI  - [Assessment of therapeutic efficacy, an essential step in evidence-based
      medicine].
AB  - Evidence-based medicine relies on the results from clinical trials. We will
      describe the various modes of expression of the results (absolute risk reduction,
      relative risk reduction, odds ratios, number needed to treat to avoid one
      event,...) and we will insist upon the clinical significance and the pitfalls in
      the interpretation of these various indices of therapeutic efficacy.

PMID- 10909302
TI  - [Evidence-based medicine. Input of epidemiologic studies].
AB  - Epidemiological studies, more specifically those related to analytical
      epidemiology are a major determinant of evidence-based medicine. When classifying
      the value of the different epidemiological studies, based on their level of
      causality, cohort studies are ranked higher than case-control studies, mainly due
      to the fact that they allow direct collection of information on exposition to
      risk factors and health consequences. However, case-control studies can also
      provide an important information, if a specific effort is dedicated to the
      analyses of the circumstances of the exposition. Meta-analysis increases, by
      pooling them, the statistical power of individual studies of limited size. Meta
      analysis can also be considered as an important source of evidence in the
      perspective of evidence-based medicine.

PMID- 10909303
TI  - [Evidence-based medicine. Input of controlled clinical trials].
AB  - Controlled clinical trials are the support of Evidence-Based Medicine. In most
      instances, only them can indeed provide the demonstration of both the efficacy
      and safety of a pharmacological treatment, based upon rigorous scientific
      experimental observations avoiding potential bias due to subjective
      interpretation. In order to be able to extrapolate conclusions of drug trials to
      clinical practice and to positively influence physician's attitudes,
      "explanatory" trials, which aim at proving the intrinsic activity of the
      molecule, should be completed by "pragmatic" trials, which aim at demonstrating
      the clinical utility of the drug.

PMID- 10909304
TI  - [Selection of EBM resources on the internet].
AB  - To integrate Evidence-Based Medicine (EBM) into practice, the physician has
      access to a number of resources on the Internet. They belong to two distinct
      groups: tools intended for EBM learning and EBM syntheses prepared by different
      international organizations. The present article presents the main EBM resources
      on the network and comments on them. These information are also available on the
      URL site: http:www.ebm.lib.ulg.ac.be/prostate/link_ebm .htm.

PMID- 10909305
TI  - [How to practically solve diagnostic or therapeutic problems in an EMB process?].
AB  - Evidence-Based Medicine (EBM) can be defined as the use of best current evidence
      from clinical research in making decisions about the care of individual patients.
      It consists of a process of turning clinical problems into questions and then
      locating the best available evidence to answer them, critically appraising the
      evidence for its validity and usefulness, and applying the findings to clinical
      practice. The present article presents the EBM principles and their application
      to diagnostic and therapeutic questions. Further detailed information on Evidence
      Based Medicine is presented at the URL address:
      http:?www.ebm.lib.ulg.ac.be/prostate/ebm.+ ++htm.

PMID- 10909306
TI  - [Problem-based learning, description of a pedagogical method leading to evidence
      based medicine].
AB  - Problem-Based Learning is an educational method which uses health care scenarios
      to provide a context for learning and to elaborate knowledge through discussion.
      Additional expectations are to stimulate critical thinking and problem-solving
      skills, and to develop clinical reasoning taking into account the patient's
      psychosocial environment and preferences, the economic requirements as well as
      the best evidence from biomedical research. Appearing at the end of the 60's, it
      has been adopted by 10% of medical schools world-wide. PBL follows the same rules
      as Evidence-Based Medicine but is student-centered and provides the information
      seeking skills necessary for self-directed life long learning. In this short
      article, we review the theoretical basis and process of PBL, emphasizing the
      teacher-student relationship and discussing the suggested advantages and
      disadvantages of this curriculum. Students in PBL programs make greater use of
      self-selected references and online searching. From this point of view, PBL
      strengthens the role of health libraries in medical education, and prepares the
      future physician for Evidence-Based Medicine.

PMID- 10909307
TI  - [General medicine: is it concerned with EBM?].
AB  - Whereas Evidence-Based Medicine (EBM) is recommended by all experts, it should be
      recognized that it remains far from the preoccupations of most General
      Practitioners (GPs). The present paper analyzes the multiple reasons explaining
      such a discordance. They can be found in the fundaments of EBM itself, in the
      characteristics of medical learning and practice and, finally, in the
      particularities of the individual patient-physician relationship. GPs should
      become active partners in the EBM process in order to influence it positively and
      not to bear it passively, for greater patient's benefits.

PMID- 10909308
TI  - [Uncertainty of practitioners between rational and evidence-based dermatology].
AB  - In opposition to intuitive and empirical approaches, rigorous medicine relies on
      two axes of development. Evidence-Based Medicine is currently put forward.
      However, it can not replace rational medicine rooted in physiopathological
      explanations. Dermatology does not escape such conceptual duality.
      Dermatopathology is one major pillar of rational dermatology. Such situation is
      jeopardized by health planners who deny the perennial skill of dermatologists and
      concede hegemony of dermatopathology to general pathologists.

PMID- 10909309
TI  - [Relativity of the management of skin cancers. A plea for synergy between general
      practitioners and the dermatologist-oncologist].
AB  - The clinical diagnosis and treatment of cutaneous cancers represent a frequent
      situation in cancerology. About one third of all human cancers take their origin
      from the skin. The general practitioner and the dermatologist-oncologist play the
      key role in that field of health care.

PMID- 10909310
TI  - [The "guidelines" of contemporary medicine. What do they represent? What
      potential implications can one expect? What one must require?].
AB  - What are exactly clinical guidelines? By whom are they prepared, for which
      purpose and how? They are supposed to help the practitioner select the most
      appropriate therapy in a given clinical situation, but do not they represent a
      threat to medical freedom? Will not they one day acquire legal or economic
      implications? What are the basic requirements for clinical guidelines to become
      widely accepted? The answers given to those questions by recent important
      publications are summarized in this article.

PMID- 10909311
TI  - [On the inapplicability of certain therapeutic guidelines in practice: the
      example of reimbursement for hypolipidemic agents in Belgium].
AB  - International guidelines from the Task Force of European and other Societies on
      Coronary Prevention and national guidelines from the Belgian Lipid Club recently
      emphasized the potential interest of adequate management of patients with even
      moderate hypercholesterolaemia. However, current criteria for the reimbursement
      of lipid-lowering drugs in Belgium do not allow to follow these guidelines. A
      solution should be urgently found in order to bridge the gap and permit
      practitioners, after diet failure, to effectively prescribe lipid-lowering agents
      in patients who should benefit in priority of such a treatment. It is certainly
      the case in secondary prevention as well as, in high risk individuals, in primary
      prevention, i.e. in situations where these drugs have provided enough evidence of
      their efficacy with an acceptable cost-benefit ratio.

PMID- 10909312
TI  - [Hypertension 2000. Medical guidelines based on scientific evidence].
AB  - The benefit of antihypertensive therapy has been clearly established in mild to
      moderate as well as in severe hypertension. The benefit appears related to the
      correction of high blood pressure and the nature of the antihypertensive agents
      used to reach that goal is of secondary importance, excepted in some specific
      clinical situations. Additional benefits have clearly been established for the
      use of betablockers in myocardial infarction, ACE inhibitors in diabetes mainly
      with proteinuria and proteinuric nephropathies. The availability of different
      pharmacological classes allows the clinician to personalize the treatment to the
      individual characteristics of the hypertensive patient.

PMID- 10909313
TI  - [Diagnosis and treatment of heart failure].
AB  - The incidence of heart failure is consistently progressing among our population;
      it now represents a major problem of public health and is extremely costly for
      our health system. Over recent years, several well controlled studies have been
      devoted to heart failure. They allow to propose guidelines which fulfill all the
      requirements of Evidence-Based Medicine. These recommendations, however, are not
      always easy to apply in the individual patient. Guidelines for the sometimes
      difficult diagnosis of heart failure will be reviewed. On the basis of the
      results of large controlled clinical trials, we shall envisage the comprehensive
      treatment of a heart failure patient taking into account the functional class as
      well as some individual characteristics (age, presence of hypertension, atrial
      fibrillation, renal insufficiency). The different pharmacologic agents which have
      demonstrated efficacy will be reviewed and the strategies to avoid the potential
      pitfalls of their simultaneous use will be indicated. The key role of the general
      practitioner in the surveillance and titration of heart failure therapy will be
      emphasized.

PMID- 10909314
TI  - [Acute myocardial infarction: management, prognosis and survival].
AB  - Acute myocardial infarction (AMI) is a serious condition which requires rapid
      hospital management. In this article, we review the current recommendations
      concerning AMI treatment, as well as our therapeutic approach, which is based on
      the evidence provided by several large well controlled clinical trials. Mid and
      long term prognosis are mainly related to the development of left ventricular
      dysfunction which determines heart failure, the occurrence of severe ventricular
      arrhythmias and the persistence of residual myocardial ischemia. Several
      treatments (aspirin, beta-blockade, ACE inhibitors, statins) have shown their
      benefit in terms of secondary prevention.

PMID- 10909315
TI  - [Treatment of unstable angina].
AB  - Unstable angina generally is a serious condition which often requires hospital
      treatment. In this review article, we shall describe our therapeutic approach to
      unstable angina. It is almost identical worldwide. This attitude is based on the
      evidence provided by well controlled clinical trials. It is therefore a good
      example of Evidence-Based Medicine.

PMID- 10909316
TI  - [Treatment of chronic angina pectoris].
AB  - Stable angina is one of the manifestations of coronary artery disease. In this
      review, we shall define the clinical criteria for the diagnosis of angina. The
      different techniques of evaluation will be discussed with a particular emphasis
      on the international recommendations for the use of coronary arteriography. The
      different therapeutic modalities will be outlined based on the results of large
      controlled clinical trials. Finally, the guidelines proposed for the use of
      coronary by-pass surgery and PTCA will be reviewed.

PMID- 10909317
TI  - [Antithrombotic therapy of atrial fibrillation].
AB  - Atrial fibrillation is a major source of stroke. During the past decade, large
      trials demonstrated the efficacy of anticoagulation and, to a lesser extent,
      aspirin in primary and secondary prevention of stroke in high risk patients with
      atrial fibrillation. In this article we reviewed the results of these studies and
      we present the current guidelines for the antithrombotic treatment of atrial
      fibrillation.

PMID- 10909318
TI  - [Evidence-based medicine. Indications for cardiac pacemakers].
AB  - Recently published international recommendations classify indications for
      permanent cardiac pacing according to their level of evidence of clinical
      benefit. Sick sinus syndrome, AV conduction disturbances, carotid sinus
      hypersensitivity and congestive heart failure are successively discussed. Good
      quality practice not only includes careful indication analysis but also a
      rational choice of pacemaker type. In sick sinus syndrome, the clinical interest
      of physiological pacing modes clearly appears, particularly in the prevention of
      atrial fibrillation.

PMID- 10909319
TI  - [Utilization of implantable ventricular defibrillators (with an analysis of the
      value of antiarrhythmics in the treatment of potentially fatal ventricular
      arrhythmias].
AB  - During the past 15 years, the efficacy of antiarrhythmic drugs has been
      investigated for reducing sudden cardiac death in patients at high risk of
      arrhythmia. Whereas the benefits of beta-blocker therapy are well established, a
      reduction in mortality with other antiarrhythmic drugs remains unproved and in
      some cases, there is evidence of increased mortality with class I and some class
      III agents. At the same time, the development of the automatic implantable
      cardioverter-defibrillator has been one of the spectacular achievements in
      cardiology. It has altered the therapeutic landscape for patients with
      symptomatic ventricular tachycardia or cardiac arrest. In these patients, the
      automatic implantable defibrillator is clearly first line therapy, as recognized
      by the international scientific cardiac societies guidelines.

PMID- 10909320
TI  - [Atherosclerotic pathology of the aortic arch and cerebrovascular accidents].
AB  - Over the last 10 years, transoesophageal echocardiography has allowed the
      visualisation of the particularly frequent atheromatous involvement of the
      initial part of the aorta in patients suffering from cerebral as well as
      peripheral embolism. Recent studies have shown that atherosclerosis of the
      initial, precarotid, part of the aorta is both a marker of general as well as
      coronary atherosclerosis and an important, accident independent risk factor of
      recurrence of stroke. The therapy of these aortic lesions is still currently
      under debate and there are no published guidelines about this issue in the
      literature. We therefore have applied the Evidence-Based Medicine information
      gathering method described earlier in this journal in order to better define the
      best therapeutic approach of this type of pathology.

PMID- 10909321
TI  - [What is your diagnosis? Severe osteoporosis with pathological fracture of
      thoracic vertebrae 6+7].

PMID- 10909322
TI  - [Research in general practice. Plea for organized and high quality clinical
      research by general practice physicians in Switzerland].
AB  - The clinical research in the practitioner's office is indispensable for the
      teaching of the medicine of first recourse. On the basis of the analysis of 109
      publications, the authors propose to structure this research under the shape of
      investigator's networks while guaranteeing an interface between the primary care
      physicians and the academic specialists. To realise this network, an
      institutional support is necessary.

PMID- 10909323
TI  - [Anemia in HIV infection].
AB  - Anemia is a common finding in HIV-infected patients, especially in late stages of
      the disease. The grade of anemia is an independent marker for mortality. Beside
      the classical causes of anemia we find in HIV-infected patients typically
      cytokine mediated suppression of the bone marrow, infiltration of the latter by
      opportunistic agents and side effects of drugs. These causes have to be taken
      into account in the diagnostic approach. The therapeutic intervention should be
      focused on the aetiology and pathogenesis of anemia in the individual patient.
      Successful antiretroviral combination therapy is associated with a substantial
      decrease of morbidity and mortality and lowers the incidence of severe anemia.
      However, several antiretroviral agents, especially zidovudine, and drugs against
      opportunistic infections can cause anemia.

PMID- 10909324
TI  - [Acute mesenteric ischemia: value of computerized tomography diagnosis].
AB  - Acute mesenteric ischemia (AMI) is an acute life-threatening vascular emergency.
      Clinical presentation is often unspecific. Rapid diagnosis and therapy are
      essential in survival. Contrast-enhanced spiral computed tomography is sensitive
      and highly specific in the diagnosis of AMI.

PMID- 10909325
TI  - [Progressive, small spotted, confluent erythema with bullae formation and general
      symptoms. Acute Lyell syndrome].

PMID- 10909326
TI  - [Raynaud phenomenon. Mixed connective tissue disease].

PMID- 10909327
TI  - [The elderly, the aged...: who are they?].

PMID- 10909328
TI  - [Nurse-patient communication concerning the education of the diabetic patient:
      revision of a protocol].
AB  - The educational process of a diabetic patient is a long life experience. The
      monitoring experience of the educational activity with diabetic patients is
      described. Nurses working at the Diabetic Centre in Rovigo perceived difficulties
      in the communication with IDDM patients (Insulin Dependent Diabetes Mellitus)
      especially at the first diagnosis of the disease and during the first patients'
      encounters. A thorough assessment of the nurse patient communication (analysis of
      the problems perceived and specific problems encountered; videotapes of nurse
      patient communication and discussion with the psychologist on the verbal and non
      verbal communication styles adopted; discussion with the team on the content of
      the communication) was the occasion for modifying the information protocols. The
      experience involved also the nurses caring for patients in the general wards, in
      order to guarantee continuity in care and information between the ward and the
      Centre. A 'Survival Kit' for newly diagnosed IDDM patients was devised and an
      agreement was reached not only on contents to be taught during the first
      encounters but also on skills that the patients is expected to acquire and on the
      teaching methods.

PMID- 10909330
TI  - [Survey of measures for the prevention of infections in bone marrow
      transplantation centers].
AB  - This paper reports on the results of a survey conducted on the organization of
      bone marrow transplant (BMT) centers in Italy, with particular attention to the
      measures routinely adopted for the prevention of infectious complications in BMT
      patients. In 1997, a questionnaire containing 53 questions with multiple-answers
      and 15 with single-answer was sent to the 65 Italian BMT centers. The topics
      addressed in the questionnaire were the following: general structural
      organization of the BMT center; personnel organization; type of transplants
      (autologous, allogenic, both); type of protective environment; hygiene measures
      and food; management of central venous catheters; microbiological surveillance.
      Fifty questionnaires out of 65 (77%) were available. The analysis of data
      indicated that most centers (more than 60%) use complex and multiple measures for
      the prevention of infections. These are mainly represented by careful personal
      hygiene of the patient, protective isolation of the patient from other patients
      and relatives; careful washing of personnels' hands before entering patients
      room; extensive microbiological surveillance. Furthermore, 52% of BMT centers
      adopt additional measures, such as filtered air, while 22% of centers, on the
      contrary, lack any air-conditioning apparatus. Overall, the results of the survey
      indicate that there is a substantial variability in the adoption and evaluation
      of the impact of such different measures on the incidence of infectious
      complications after BMT.

PMID- 10909329
TI  - [Characteristics of nursing students attending the University Courses for Nursing
      Diploma at Trento: reasons for their choices in the first trimester].
AB  - Motivations and reasons for the choice of the nursing course were explored in the
      students applying for the university nursing courses from 1995 to 1998. Aim of
      the study was to trace a picture of students' characteristics but also to have
      elements to promote campaigns for increasing the number of applicants. Overall,
      183 first year students (70 in 1995; 60 in 1996 and 53 in 1997) were administered
      a questionnaire with questions related to socioanagraphic data, reasons for the
      choice of the University Diploma in Nursing Sciences (DUSI) and aspects of the
      nursing profession considered positive and negative. The 87% of the students had
      previous work experiences, more than 20% in the health field and a larger number
      in the social field. The main reasons for choosing the DUSI are the strong
      connections between theory and practice and the opportunity of working soon after
      the course. Fifty per cent of the students make definitely up their mind on the
      final choice of becoming a nurse during the course: in fact only 55% of the
      students are moderately-strongly convinced of practising the nursing profession
      when they enter the curriculum. The data are commented on with special attention
      to the implications for the contents and strategies of a campaign or ad hoc
      initiatives aimed at increasing the number of students that apply to the nursing
      courses.

PMID- 10909331
TI  - [Care for the elderly, nursing homes and care givers].

PMID- 10909332
TI  - [Acute states of mental confusion in the hospitalized elderly].

PMID- 10909333
TI  - [Words of expectation, research, preparation and accomplishment of peace].

PMID- 10909334
TI  - [A narrative approach to assistance to the elderly. Suggestions for adult
      education in caring for the elderly].

PMID- 10909335
TI  - [Suppression?].

PMID- 10909336
TI  - [Strike!].

PMID- 10909337
TI  - [On the topic of grand rounds--relaxing dialog or uneasy situation?].

PMID- 10909338
TI  - [World Health Organization: "Health 21"].

PMID- 10909339
TI  - [Relational nursing].

PMID- 10909340
TI  - [Congress 2000: interesting days in Vienna] [In Process Citation]

PMID- 10909341
TI  - [Experiment or reform?].

PMID- 10909342
TI  - [The selfless registered nurse: image of the profession, evaluation by others,
      requirements for the role. A discussion within the framework of the youth
      project].

PMID- 10909343
TI  - [Supervision for the nursing professions].

PMID- 10909344
TI  - [Professional development of the "nurse" from 1850-1950. A historical paper on
      the development of nursing].

PMID- 10909345
TI  - [Experiences with inservice training--a report].

PMID- 10909346
TI  - [Diagnosis in nursing].

PMID- 10909347
TI  - [How do I tell my children?] [In Process Citation]

PMID- 10909348
TI  - [12 May 2000--day of the nurses. On May 12 we celebrate the Day of the Nurses for
      the first time in this millennium--a summary of the ideas of the International
      Council of Nurses] [In Process Citation]

PMID- 10909349
TI  - [More optimism for nursing].

PMID- 10909350
TI  - [The new government: its attitude to nursing].

PMID- 10909351
TI  - [Nursing diagnoses are still a "hot iron" in nursing theory and practice.
      Interview by Harald Verworner].

PMID- 10909352
TI  - [Nursing diagnosis and problems of nursing classification].

PMID- 10909353
TI  - [Licensure in nursing: a near future prospect].
AB  - The Spanish Association of Education in Nursing convoked an important meeting in
      Seville, this past March, to clarify ideas and generate constructive debate
      regarding the future of a licentiate degree in Nursing in our country. Maria
      Duran, Rosemaria Alberdi, Jose A. Martos and Jesus Sanz Villorejo attended this
      meeting. Over the course of the ensuing debate, the whole evolutionary process up
      to the present time was explained and the conferees expressed the need to form a
      consensus among all the institutions involved in the Spanish nursing profession.

PMID- 10909354
TI  - [Indications and administration: home oxygen therapy].
AB  - At the present time, it has been clearly demonstrated that at home oxygen therapy
      either on a long term basis or on a continuous basis brings important benefits
      for a patient: his/her physical and neuro-psychological conditions improve and
      his/her quality of life increases. However, given that this is some controversy
      about its indications, therapeutic effects and manner to administrate it, the
      authors review all these aspects, drawing from very up-to-date bibliographical
      references. At a later date, in another article, these same authors will evaluate
      nursing treatment corresponding directly to at home oxygen therapy.

PMID- 10909355
TI  - [Depression 1. Clinical aspects and nurses' evaluation].
AB  - OBJECTIVES: To review the recent advances made in evaluation and treatment
      procedures in cases of depression and their repercussions in nursing care. The
      growing efficiency of antidepressive medication, together with the importance
      given to community awareness of the upheavals which affect mental health, have
      modified the role nursing plays in evaluation of patients suffering depressive
      episodes. In this changing context, the therapeutic relationship between nurse
      and patient has developed into one of the pillars which sustain a correct and
      long-lasting stability in the depressed patient's state of mind. SOURCES: Primary
      source information on treatment methods by nurses handling depressed patients
      published from 1995 through 1999 and identified in the Medline data base. In a
      second article, these same authors will evaluate the intervention and the follow
      up procedures carried out by nurses caring for patients suffering from
      depression.

PMID- 10909356
TI  - [Clinical evaluation of a new device for patients with colostomies].
AB  - INTRODUCTION: There are some 32,000 people in Spain who have undergone an
      osteotomy; of these, approximately 76% have a colostomy. While a patient
      undergoes rehabilitation, it is essential that the collecting device provide the
      patient security, cutaneous protection, effectiveness against odors and
      discretion; all of which can greatly help a patient to accept his/her new body
      image, to recover his/her self-esteem and to reincorporate into his/her normal
      life. In order to attend to the ever more demanding demands placed by this body
      of patients, a new closed one piece bag named "Alterna Ideal" has been developed.
      The purpose of this clinical test is to show the efficiency of this product under
      real treatment conditions. MATERIALS AND METHODS: This prospective, open multi
      centric and non-comparative study permitted both patients and nursing
      professional to evaluate Alterna Ideal under habitual use conditions. Each
      patient tested 19 bags and made two check-ups with health professionals, one at
      the beginning of this study and the other at the end of it. Besides the
      demographic data, the evaluating parameters referred to the four elements which
      make up this device: an adhesive component, a filter, a soft cover and its shape.
      At the same time, the product as a whole was evaluated along with its duration, a
      patient's preference for it over the previously used product and the condition of
      the skin in the colon area at the beginning and the end of this test. To analyze
      data, descriptive statistics were used. RESULTS: This study included 187
      patients, 54.5% were male and 45.5% female; average age was 61.9 years. The
      average stoma diameter was 33.7 mm; the average time since a patient underwent
      his/her colostomy was 25.2 months; 82.4% had surpassed one month since their
      osteotomy. 79.1% of these patients did not show any complication related to their
      osteotomy. The average length of use of these bags was 13.37 hours. Statistically
      significant differences were obtained regarding the condition of the skin in the
      colon area since this condition improved as this study progressed. These are the
      percentages of patients who rated each of these concepts as either good or very
      good: immediate application, 91.5%; feeling of security, 85.6%; flexibility and
      adaptability, 90.9%; effectiveness against leakage, 85.5%; removal, 91.5%; the
      filter's functioning, 88.2%; the shape of the bag, 92%; the quality of the soft
      covering, 94.7%; and overall rating, 92.5%. 75.9% of these patients who had
      previously used another product stated they preferred Alterna Ideal. These are
      the percentages of professionals who rated each of these concepts as either good
      or very good: the setting, 95.7%; cutaneous protection, 94.7%; the filter's
      functioning, 93%; the shape of the bag, 95.7%; the quality of the soft covering,
      98.4%; and overall rating, 97.3%. 96.8% of the professionals involved in this
      study stated they would recommend this product in the future. COMMENTS: The
      results of this study confirm the effectiveness of Alterna Ideal as a collecting
      device for persons who have undergone a colostomy. This product is a highly
      valuable therapeutic alternative which can aid this group of patients to enjoy an
      improved quality of life.

PMID- 10909357
TI  - [Natural nutrition and diet therapy].

PMID- 10909358
TI  - [Left wrist (dorsal view)].

PMID- 10909360
TI  - [Active strategies for the prevention of pressure ulcers].

PMID- 10909359
TI  - [An alternative therapy: the insulin pump].

PMID- 10909361
TI  - [Patients with intraaortic counterpulsation balloons: nursing care].
AB  - The authors present a plan of basic treatment for patients which carry an
      intraaorto counterpulsation balloon, abbreviated "BCIA", which makes it possible
      to unify treatment rules in order to contribute to a fine development and follow
      up on these patients and thus guarantee the continuity and quality of their
      treatment and care in each of the three phases in which nurses actively
      participate. The method used for the elaboration of this plan is based on the
      bifocal clinical nursing model proposed by L.J. Carpenito.

PMID- 10909362
TI  - [The elderly with AIDS. Case report].
AB  - When we speak about AIDS, even today, we rarely associate it with the elderly.
      Nonetheless, nursing care reality demonstrates that AIDS cases are more numerous
      all the time inside this population group known as the third generation. We
      should not forget that sex is a personal experience that can be practiced at all
      ages, and is not limited only to the young, and that preventive measures are
      necessary in all situations. Therefore, it is interesting to share what these
      authors reflect about this topic; they refer to a real case. It will probably be
      necessary to change the established schemes and consider this age group to be one
      in need of information on the possibilities of contagion. It will also be
      essential to carry out faster diagnoses and to develop educational measures as
      well as continuing professional development procedures in order that the elderly
      be considered susceptible to suffer this disease and to improve the treatment
      provided to the elderly. AIDS does not discriminate. Therefore, we cannot
      discriminate either.

PMID- 10909363
TI  - [Depression. 2. Treatment and nursing interventions].
AB  - OBJECTIVES: To review the recent advances in the evaluation and treatment
      procedures for depressive episodes and their repercussions on nursing care. The
      growing effectiveness of anti-depressive medication, together with the importance
      provided by community understanding of mental health disorders, have modified the
      role nurses play in evaluation (Part One in Revista ROL de Enfermeria 23(4):265
      270), intervention and follow up (Part Two) for patients suffering from
      depressive episodes. In this context of change, the therapeutic relationship
      between nurse and patient has developed into one of the pillars which maintains a
      correct and long-lasting stabilization of a depressed patient's state of mind.
      SOURCES: Cases identified by Medline database referring to nursing treatment of
      patients suffering from depression, published from 1995 until 1999.

PMID- 10909364
TI  - [Children with asthma: hospital care].
AB  - During this period of the year, asthma becomes a much more important problem for
      many young children and their families than during other periods of the year. In
      this article, the authors describe the factors which produce this problem, how a
      child should be cared for immediately, which type of complementary tests are
      recommended, what the medical care should entail and what the nursing treatment
      should consist of. The final objective of all this is to enable the asthmatic
      child to carry on his/her normal lifestyle.

PMID- 10909366
TI  - [The Society of Community Nurses celebrated its 3rd successful congress].

PMID- 10909365
TI  - [Work satisfaction and associated factors among nursing personnel: Navarra
      Hospital].

PMID- 10909367
TI  - [The second cycle in nursing. A project of historical continuity].
AB  - The year 2000 broke out with a controversial and accelerated debate about a
      Licentiate for Nursing, a project which has been developing since the beginning
      of the nineties as a result of a series of demands and projects presented earlier
      on. In this article, Marta Duran, a well-known prestigious professional who is
      playing an important, leading role in this whole process, presents the academic
      and disciplinary benchmarks which, in her opinion and based on a rigorous, well
      founded position, should be those which enable us to select a model that covers
      the expectations opened up by this project. The issue is dealt with from the
      following perspectives: the context of human and social development and the
      academic proposal for the development of nursing.

PMID- 10909368
TI  - [Left pubic nerve and lumbosacral plexus].

PMID- 10909369
TI  - [Cubital nerve injury].
AB  - One of the more frequently accomplished treatment job in the nursing profession
      is blood extraction. The preferred location is the elbow flection, in the
      cephalic or basilic veins. Puncture in one of those veins may produce a series of
      complications as described in every procedure handbook in print. One of them,
      very rare, is the punction of cubital nerve that may lead to serious consequences
      for the patient.

PMID- 10909370
TI  - [Innovations and new techniques: tracheostomy cannulas].
AB  - In recent years, therapy by means of a tracheostomy has increased considerably
      due to the use of new trachea opening procedures and the development of the
      newest generation of tubes employed in tracheostomy. Percutaneous tracheostomy
      has become the preferred choice technique for patients in critical condition
      since it is a simple procedure, almost bloodless, and furthermore, this procedure
      can be carried out on a patient in a bed in a normal ward. The translaryngeal
      tracheostomy is one of the newest innovative techniques performed from inside the
      trachea; due to its complex nature, it is not commonly used yet although it
      promises to be an alternative procedure when confronting various counter
      indications found in the percutaneous technique. In addition to the development
      of these techniques, substantial design modifications in the tubes used in
      tracheostomy have been produced; their objectives include improving a patient's
      comfortableness, reducing complications and easing a nurse's work.

PMID- 10909371
TI  - [Challenges to nursing organizations at the start of a new era].

PMID- 10909372
TI  - [Nursing specialization program: residential model: experience of establishing
      oneself in a teaching hospital].
AB  - This is a report about the experience of setting up a Specialization Program for
      Nurses in a "Residence" format, at the school-hospital of the Federal University
      of Sao Paulo, which mixes the traditional structure of specialization programs in
      Brazil with the model of the resident physician practical training. It began on
      February 1995, with the following objectives: 1) to qualify nurses, in different
      specialities, by an intensive training program, on a full-time schedule; 2) to
      contribute to improve the process of nursing care and; 3) to increase the quality
      of nursing assistance in our hospital. The results of our experience allow us to
      suggest that's a good way to qualify nurses for the best nursing practice, and to
      increase nursing research in a very practical basis.

PMID- 10909373
TI  - [Teaching psychiatric nursing in Ceara: a reality in outline].
AB  - The teaching of Psychiatric Nursing Course in the Nursing Undergraduate Programs
      in Ceara, topic of this study, is a reality that has been building up, fusing
      itself, in a broader context, the teaching of Nursing as a whole. To study it,
      attempts have been made in order to go deep in the Institutions' formal
      discourse, (Syllabuses, Course Programs) and in the ideological discourse of
      social actors which are responsible for the passing on the knowledge absorbed
      there, produced and reproduced. In the analysis under a structural-historical
      approach it has been possible to notice that the Psychiatric Nursing Courses are
      going through a moment of reflection, uncertainties and changes which have been
      originated by the process of syllabus reform and of the psychiatric assistance.
      The change of paradigm still turns out be an utopia, not wholly shared by
      everyone concerned, yet searched for by the majority.

PMID- 10909374
TI  - [Critical thinking: a focus in nursing education].
AB  - In this study we identify and analyse articles published in national and
      international journals, that used the term "critical thinking" in the title or
      summary. The aim of the analysis was to seek answers to educators' queries as to
      how to improve teaching-learning the process in nursing. We analysed 52 articles
      published in the indexes Comprehensive Medline, Lilacs and Cinahl, in the last
      five years, from July, 1992 to July, 1997. Data analysis showed that critical
      thinking should be implemented in nursing education, what demands syllabus
      planning and teaching-learning strategies that will favour active participation
      by both educators and learners.

PMID- 10909375
TI  - [Social perceptions of nurses].
AB  - The purpose of this study was to scale nurses' social perception through the
      psychophysics method of category estimation. Therefore, undergraduate students
      from the areas of psychology, nursing, dentistry and medicine were invited to
      participate in the study. Results showed: 1) in our environment the
      characteristic tidy has a central role, and with the characteristic responsible
      form nurse's stereotype and 2) the high correlations among the category
      estimations of the sub-groups reflect a great concordance in the levels of
      attributions given by different samples of university students regarding the
      characteristics of the nurse professional, indicating that the estimations are
      stabilized among the samples.

PMID- 10909376
TI  - [Quality management: its use in nursing].
AB  - The Quality Management has been used and it is a reality in the hospitals. Thus
      the authors comment about its importance for Nursing and analyse its utilization
      in a Nursing Service of a private hospital, with purpose to evaluate the
      implementation form, nurses' involvement and the Deming' Principles application.
      Data show that the implementation has brought good results, nurses are engaged in
      the process and the Deming's Principles have been utilized, adequate or
      inadequately.

PMID- 10909377
TI  - [Surgical patients and their anxieties].
AB  - This study aims at giving theoretical aspects of the anxiety and discussing about
      the difficulty faced by nurses to evaluate the emotional state of the patient,
      considering that the theoretical basis of the nurse is not enough to interfere in
      this situation.

PMID- 10909378
TI  - [The cultural meaning of cerebral aneurysm and its treatment for the patient and
      his family: an ethnographic study].
AB  - This is a descriptive ethnographic study with 13 patients with cerebral aneurysm
      and their relatives aiming at understanding the meaning of the illness and the
      treatment. The data were collected by interviews and observations during the
      hospitalization and, after the discharge, in the outpatient clinic and at home.
      The central theme obtained from the study was "It had to be for me! God knows
      what He does". This theme reveals a religious interpretation for the illness and
      a magic basis for its cure. Thus, cerebral aneurysm is interpreted as a material
      illness (body) and a spiritual illness (soul).

PMID- 10909379
TI  - [The effect of sugar on the process of cicatrization of infected surgical
      incisions].
AB  - This is an experimental research based on microbiological analysis. Our aim was
      to evaluate the influence of sugar on the healing process of infected surgical
      wounds in 25 patients. On the dehiscences, there have been identified gram
      positive and gram negative bacteria, and fungi as well. Every patient was
      administered systemic antibiotics and had the wounds treated locally with crystal
      sugar three times a day. Statistics showed, by Person's correlation, that sugar
      did not influence on the healing process of infected surgical wounds in
      undernourished, overweight and elderly individuals.

PMID- 10909380
TI  - [Monitoring of Staphylococcus aureus colonization in students of a course for
      nurses aides during their professional education].
AB  - Considering our goal of understanding the colonization by Staphylococcus aureus
      in students from a nursing auxiliary program, during their professional
      formation, we collected material from the nasal cavity (N), right (Md) and left
      (Me) hands from 42 students on different moments of their formation relating the
      levels of colonization to the activities developed during the program. Results
      showed an oscillation in the colonization rate in different moments and the
      possibility of agent reciprocal transmission between the students and the taken
      care receptors, considering the type of contact.

PMID- 10909381
TI  - [The nurse's role in the rehabilitation of the elderly].
AB  - As the elderly people in our country are increasing it becomes more and more
      frequent the elderly's presence in the services of health and especially of
      rehabilitation. We bring in this descriptive text the main aspects involved in
      the elderly's rehabilitation: the referring peculiarities to the rehabilitation
      in this age group, the functional evaluation as an important indicative of the
      life quality, the phases of the elderly's rehabilitation and the systematized
      nursing care through the nurse, inserted in the multidisciplinary team acts with
      the elderly patient and his family, in an individualized way.

PMID- 10909382
TI  - [A family's experience of home accidents--report of an experience].
AB  - This study aims at knowing the behaviour of the family facing the home accidents
      among children, identifying the risk factors in the home environment, in the
      family's perception and analysing the socioeconomic-cultural context contributing
      to the occurrence of children's home accident. The work was made in a family that
      had experienced a case of poisoning of a 4 year-old child. Participant
      observation and the semi-structured interview were used as methodology. The
      results evidenced that the family constantly lives among children's home
      accidents and the socioeconomic-cultural context has a strong influence in the
      amount and quality of these cases.

PMID- 10909383
TI  - [Contact with violence--health professionals and their patients victims of
      abuse].
AB  - Using qualitative methods of collecting data and analysis, this article outlines
      the way health care professionals, mainly pediatricians, feel about violence and
      their responsibility in denouncing the cases which they were forced to deal with.
      Although a typical "case study"--the experience in Instituto Fernandes
      Figueira/FIOCRUZ--the major concern of this work is to offer material for
      reflexion about procedures that should or could be taken in face to child
      morbidity caused by "external causes", making suggestions for a health conduct
      that enhances the relationship between violence and the medical practice related
      to child and adolescent abuse.

PMID- 10909384
TI  - [Health care for children: perspectives for community health services].
AB  - The study aims at analysing the community health nursing practice in the care of
      children and to point out the perspectives for the coming millennium. The study
      was conducted by review of the literature. It provides a brief synthesis of the
      current social context and a short historic reflection about health practices
      with children and community health nursing practice. It is observed that the
      practice of nursing is conducted according to the official Health Assistance
      Program for Children. Despite its goals, however, the program has not been
      efficient. In this way it will be valued the multiprofessional work in the
      accompaniment of the growth and development, domiciliary visit, and "groups of
      mothers" in which the nurse will be a co-participant of the staff, with the great
      contribution that health professionals with preventions and promotions background
      frequently offer.

PMID- 10909385
TI  - [Sexual activity and sexually transmitted diseases in high school students in Rio
      Branco-Acre, Brazil].
AB  - This study was realized with 2.684 students of the high school in Rio Branco
      Acre, Brazil, to verify aspects of the sexual activity and the occurrence of
      DST/AIDS. From the researched students, 48.9% had sexual intercourse, and the
      largest frequency was 34.3% for male sex, with the beginning at 13 years old, and
      for female sex 31.6%, with the beginning at 16 years old. The occurrence of
      mentioned DST/AIDS was: 58.4% for Hepatitis B, 39.4% for Moniliase and 2.2% for
      Gonorrhea. Among those ones who had their first sexual intercourse, 47.6% were
      with the boyfriend, 25.8% with the neighbor and 10.5% with the domestic maid.
      Concluding, the students who had sexual intercourse were 52.3% of private
      schools, 50.0% of federal ones, 45.7% of state ones and 41.8% of municipal ones.

PMID- 10909386
TI  - [General aspects of the sexuality of patients with pulmonary tuberculosis, cared
      for at basic health units in Ribeirao Preto-SP].
AB  - This descriptive study was carried out in order to identify and analysing the
      knowledge that the patients with pulmonary tuberculosis have about the disease
      and the experiences which they have passed through; to identify some aspects
      related to their sexuality's changing after acquiring the pulmonary tuberculosis
      and characterizing the living experiences toward their family, the
      friends'/relatives' reactions and the emerging feelings. Fifty sexually active
      patients were interviewed. The results showed that 15 (30.0%) patients with
      pulmonary tuberculosis did not have any knowledge about the disease and 32
      (64.0%) did not know how to prevent it. Among the fifty patients interviewed, 29
      (58.0%) have realized negative reactions. The pulmonary tuberculosis do not
      interferes directly only in these sexual and social people's lives, but also in
      their partners social lives. This fact has been contributing in order to decrease
      their sexual relations often.

PMID- 10909387
TI  - [Negative attitude of patients, in an intensive coronary care unit, with oro
      tracheal intubation: effects of the presence of a camera].

PMID- 10909388
TI  - [The students' page: an album for the education of laryngectomized patients].

PMID- 10909389
TI  - [Accreditation, for whom, why and how?].

PMID- 10909391
TI  - [Treatment and control of depression] [In Process Citation]

PMID- 10909390
TI  - [Role of the nurse in the prevention of diabetic complications].

PMID- 10909393
TI  - [Anxiety or depression? Diagnostic symptoms].

PMID- 10909392
TI  - ["The burden of being oneself"].

PMID- 10909394
TI  - [Psychotherapy of depression].

PMID- 10909395
TI  - [Antidepressive treatment and role of the nurse].

PMID- 10909396
TI  - [A particular case of suicidal risk].

PMID- 10909397
TI  - [Depression and circle of family and friends].

PMID- 10909398
TI  - [Pressures ... from all directions].

PMID- 10909399
TI  - 29th Annual scientific meeting of the International Society for Experimental
      Hematology (ISEH). Tampa, Florida, USA. July 8-11, 2000. Abstracts.

PMID- 10909400
TI  - International Association for Dental Research divisional and sectional abstracts.

PMID- 10909401
TI  - Turning back the clock. Has aging become a 'disease' again--to be prevented,
      treated, and even cured?

PMID- 10909402
TI  - Lipid lowering 'not always worthwhile'.

PMID- 10909403
TI  - 'Skilled trade' physicians can be noble every day.

PMID- 10909404
TI  - Diffuse thinning of scalp hair.

PMID- 10909405
TI  - Lyme disease 2000. Emerging zoonoses complicate patient work-up and treatment.
AB  - Lyme disease and other tick-borne diseases affect all age groups, including
      active persons age 50 and older. There has been a steady expansion in case
      numbers and the geographic borders of Lyme disease over the last two decades.
      Better recognition of two emerging tick-borne zoonoses (babesiosis and human
      granulocytic ehrlichiosis) that can be co-transmitted with Lyme disease is
      changing the approach to diagnosis and treatment of Lyme disease. Advances from
      genetic cloning have improved our understanding of the immune mechanisms
      associated with treatment-resistant Lyme arthritis and enabled the development of
      the first Lyme disease vaccine. The available vaccine is less efficacious in
      persons age 65 and older than in younger adults, but it may be a useful adjunct
      to other preventive measures in areas endemic for Lyme disease.

PMID- 10909406
TI  - Anti-aging medicine. 2. Efficacy and safety of hormones and antioxidants.
AB  - Little is known about the efficacy and safety of substances that are being
      promoted to consumers as "anti-aging" therapies. Hormones such as DHEA, human
      growth hormone, and testosterone tend to decline with aging, but the therapeutic
      value of replacing them to "normal" physiologic levels has not been substantiated
      by controlled clinical trials. The best source of antioxidants is a balanced
      diet, although older patients may benefit from vitamin E supplementation.
      Providing anti-aging medicine in the primary care setting means practicing good
      medicine. It means talking to patients who request these therapies and
      understanding why they want them and how much risk they're willing to take.

PMID- 10909407
TI  - Perioperative risk. Review of two guidelines for assessing older adults. American
      College of Cardiology and American Heart Association.
AB  - Elective in-patient surgery is a common occurrence among older persons and
      primary care physicians are routinely called on to provide preoperative
      assessment and perioperative risk management of these patients. Older patients
      undergoing noncardiac surgery may be at increased risk for cardiac or
      cardiovascular complications, thus perioperative assessment of risk in this
      population is prudent. Although the range of possible screens and diagnostic
      tools can make this task unwieldly, the clinical practice guidelines make it more
      manageable. Two guidelines in particular--one published jointly by the American
      College of Cardiology and American Heart Association, the other by the American
      College of Physicians--are particularly suited to perioperative assessment and
      risk management.

PMID- 10909409
TI  - Medical research in Israel: future challenges.

PMID- 10909410
TI  - The future world of medicine.

PMID- 10909408
TI  - Migraine in older patients: a case report and management strategies.
AB  - Older patients can suffer from various forms of migraine. These patients should
      be educated regarding triggers and considered for prophylactic and acute
      treatments for frequent episodes. Practitioners should keep in mind the unique
      challenges of treating migraine in older persons and first search for other
      serious yet treatable causes for headache in these patients.

PMID- 10909411
TI  - Ongoing research on mammalian cloning and embryo stem cell technologies:
      bioethics of their potential medical applications.
AB  - Reproduction by cloning has been achieved by transfer into enucleated oocytes of
      nuclei from embryonic cells and more recently from cells of adult animals. The
      efficiency at which embryos produced by such nuclear transfers will develop into
      healthy newborns is very low but has succeeded in producing some cloned bovines,
      ovines and mice. Since the first report of sheep cloning from an adult cell in
      1997, the potential applications of reproductive cloning in human medicine have
      been envisaged amidst a flurry of moral debates. Although the technology is still
      far from being ready for any human use, it has been condemned up front. It has
      also led to irrational fantasies and fears, based mainly on the misconception
      that genetic identity means identical twin personalities. Scientific research is
      ongoing to refine the cloning technology for applications in the production of
      genetically homogeneous farm animals with useful nutritional or therapeutic
      genetic traits. A new area of research is non-reproductive therapeutic cloning
      for the purpose of producing autologous embryonic cells and tissues for
      transplantation.

PMID- 10909412
TI  - How to outfox mother nature--autoimmunity: moving from shadows to sunshine.
AB  - The morbidity and disability associated with autoimmune diseases represent a
      significant health problem. One in 31 people have one form or another of an
      autoimmune disease. Despite the avalanche of molecular data, immunogenetic
      definitions and improvements in serologic diagnosis, we are still far from
      discovering the etiologies of these diseases. For some autoimmune diseases, there
      may be a very long latency period between disease onset and clinical
      presentation. Existing therapies tend to be only partially successful and often
      accompanied by a variety of serious side effects. However, even in the absence of
      a complete understanding of the underlying genetic, environmental and
      coincidental factors that confer susceptibility to autoimmune diseases, we
      believe that it is possible to devise successful therapies by interfering with
      one or more of the pathways of destruction characteristic of a specific
      autoimmune disease. We have prepared a futuristic look at the treatment of
      autoimmune disease by extrapolation of current research directions as well as
      thoughts on new methods of delivery of recombinant monoclonal antibodies. We
      predict that we will "cure" autoimmune pathology long before we understand the
      etiology. In the case of inflammatory bowel disease, as a model, and taking
      advantage of what is known on animal studies, we illustrate the progress that has
      been made in elucidating these pathways of destruction and speculate about
      possible therapeutic approaches.

PMID- 10909413
TI  - The global threat of emerging infectious diseases.

PMID- 10909414
TI  - Anti-beta 2-glycoprotein I antibodies and anti-endothelial cell antibodies induce
      tissue factor in endothelial cells.
AB  - Anti-beta 2-glycoprotein I antibodies bind to endothelial cells through beta 2
      GPI. The antibodies are present in patients with systemic lupus erythematosus and
      antiphospholipid syndrome and are associated with the pathogenesis of the
      disease. Anti-endothelial cell antibodies that react with constitutive antigens
      on ECs are present in patients with vasculiditis and other diseases. Both types
      of antibodies can activate ECs. Frequent findings in APLS and vasculitis are
      fibrin deposits and thromboembolic phenomena. These indicate that the coagulation
      system is activated. However, the mechanism of activation is not clear. ECs
      generate tissue factor upon stimulation with various substances. In the present
      study we report that monoclonal anti-beta 2-GPI antibodies and AECAs, derived
      from a patient with primary APLS and a patient with Takayasu's arteritis,
      respectively, induce a potent tissue factor in ECs. The production of TF
      activity, TF antigen and TF mRNA is dose and time dependent. The TF activity was
      induced also by F(ab)2 but not by Fc fragments and was abolished completely by
      pre-incubation with ant-TF antibodies. The TF that is induced in ECs by AECAs
      with and without beta 2-GPI specificity may activate the coagulation and thereby
      play a major role in the pathogenesis of fibrin deposition and thrombus formation
      in diseases that are associated with the presence of these antibodies.

PMID- 10909416
TI  - Mammalian heparanase as mediator of tumor metastasis and angiogenesis.
AB  - Expression of heparan sulfate-degrading endoglycosidases, commonly referred to as
      heparanases, correlates with the metastatic potential of tumor cell lines, and
      treatment with heparanase inhibitors markedly reduces the incidence of metastasis
      in experimental animals. We purified a 50 kDa heparanase from human hepatoma and
      placenta and cloned a cDNA and gene encoding a protein of 543 amino acids. Only
      one heparanase sequence was identified, suggesting that this enzyme is the
      dominant endoglucuronidase in mammalian tissues. Expression of the cloned cDNA in
      insect and mammalian cells yielded 65 kDa and 50 kDa recombinant proteins. The 50
      kDa enzyme represents an N-terminal processed enzyme that is at least 200-fold
      more active than the full-length 65 kDa form. Processing was demonstrated
      following incubation of the full-length recombinant enzyme with intact tumor
      cells. The heparanase mRNA and protein are preferentially expressed in metastatic
      cell lines and in specimens of human melanomas and carcinomas. In the colon, both
      the heparanase mRNA and protein are expressed already at the stage of
      tubulovillous adenoma, but not in the adjacent 'normal-looking' colon epithelium.
      Non-metastatic murine T lymphoma and melanoma cells transfected with the
      heparanase gene acquired a highly metastatic phenotype in vivo. Apart from its
      involvement in the egress of cells from the vasculature, heparanase is tightly
      involved in angiogenesis, both directly--by promoting invasion of endothelial
      cells (vascular sprouting), and indirectly--by releasing heparan sulfate-bound
      basic fibroblast growth factor, and generating HS degradation fragments that
      promote bFGF activity. The angiogenic potential of heparanase was demonstrated in
      vivo (Matrigel plug assay) by showing a three to fourfold increase in
      neovascularization induced by Eb T lymphoma cells following their transfection
      with the heparanase gene. The ability of heparanase to promote both tumor
      angiogenesis and metastasis makes it a promising target for cancer therapy.

PMID- 10909415
TI  - Can we create new organs from our own tissues?
AB  - The many new technologies of the past few years have set the stage for novel
      human therapeutic methods. Identification of pluripotent stem cells as being
      capable of generating various cell types in the body, together with advanced
      genetic and cell engineering techniques, may enable the design of custom tissues
      and organs and thus solve the problem of donor organ scarcity and the need for
      immune compatibility and immunosuppression to avoid graft rejection. One of the
      most prevalent metabolic disorders that will benefit from such technologies is
      insulin-dependent diabetes mellitus. The purpose of our study is to review
      potential future methods of curing metabolic disorders such as diabetes, and
      analyze the capacity to genetically manipulate the developmental fate of a tissue
      in vivo using "master regulator" genes. We systemically delivered the homeobox
      gene Pancreatic and Duodenal Homeobox gene-1 to liver of mice, by recombinant
      adenovirus technology, and analyzed whether it induces a developmental shift
      toward a beta cell phenotype. We demonstrated that PDX-1 is sufficient to
      activate the endogenous, otherwise silent, mouse insulin 1 and 2 and pro-insulin
      convertase gene expression in liver. PDX-1 expression in liver resulted in a 25
      fold increase in hepatic immunoreactive insulin content and a threefold increase
      in plasma immunoreactive insulin levels, as compared to control adenovirus
      treated mice. Hepatic immunoreactive insulin, induced by PDX-1, was processed to
      mature mI-1 and mI-2 and was biologically active; it ameliorated hyperglycemia in
      streptozotocin-treated diabetic mice. PDX-1 has the capacity to reprogram extra
      pancreatic tissue toward a beta cell phenotype. The data provide a valuable
      approach to generate "self" surrogate beta cells that are suitable for replacing
      impaired islet cell function in diabetics.

PMID- 10909417
TI  - Neuroprotection by glutamine synthetase.

PMID- 10909418
TI  - Therapeutic angiogenesis for ischemic syndromes.
AB  - Disease caused by atherosclerosis are the most common causes of morbidity and
      mortality in western societies. The inadequacy of current therapeutic modalities
      is most pronounced in the significant proportion of patients with arterial
      obstructive disease, in whom anatomical and technical limitations rule out the
      possibility of angioplasty or surgery. Therefore, less invasive approaches are
      necessary to treat these patients. The development of collateral circulation
      improves blood flow to ischemic tissues and to alleviate ischemia-related
      symptoms. Our project concentrates on enhancement of the natural mechanism of
      angiogenesis by adenoviral based vector encoding vascular endothelial growth
      factor as an angiogenic factor. The aim of our study was to determine the
      efficacy of human vascular cell infection by adenoviral based vectors in vitro
      and in vivo. Human saphenous vein endothelial cells and smooth muscle cells were
      infected by adenoviral vectors encoding the lacZ and VEGF genes (rAdlacZ,
      rAdVEGF). VEGF expression by adenoviral vector-infected cells was detected by
      western analysis and its biological activity was examined by proliferation assay.
      The feasibility of adenoviral based gene transfer in vivo was evaluated after
      direct femoral artery injection of rAdlacZ in the rat. Vascular endothelial and
      smooth muscle cells expressed high levels of VEGF following rAdVEGF infection.
      The mitogenic effect of VEGF was validated by threefold increase in EC
      proliferation rate in comparison to the control groups. In vivo gene transfer was
      demonstrated using lacZ gene transfer to arterial wall cells in the superficial
      femoral artery. Efficient adenoviral based gene delivery was demonstrated both in
      vitro and in vivo. VEGF over-expression enhanced endothelial cell proliferation,
      which is the key step for induction of angiogenesis.

PMID- 10909419
TI  - Novel trypanosomatid small nucleolar RNAs that guide methylation: their genome
      organization, expression and potential use to direct specific methylation on
      target RNA molecules.
AB  - Trypanosomatids are the causative agent of several major parasitic diseases
      including African trypanosomiasis, American trypanosomiasis, and leishmaniasis.
      These parasites possess unique RNA-processing mechanisms including trans-splicing
      of pre-mRNA and RNA editing of mitochondrial transcripts. In this study, we
      identified a trypanosomatid novel group of small nucleolar RNAs that belong to
      the box C/D snoRNA, which were shown to guide ribose methylation on rRNA. Three
      snoRNA genes were identified; snoRNA-2 carrying a single snoRNA and g2 and b2
      coding for a single or multiple snoRNAs, respectively. Mapping of the methylation
      sites guided by snoRNA-2 using two different approaches suggest that snoRNA-2 has
      the potential to guide methylation on both 5.8S and 18S rRNAs. The trypanosomes
      follow the same guide-methylation rule established for yeast and for mammals. As
      a first attempt to change the methylation pattern of target RNAs, we generated
      transgenic parasites carrying the B2 and snoRNA-2, which were engineered to shift
      the methylation site on rRNA. Despite efficient expression of these tagged
      snoRNAs, the novel methylation site was not generated. However, efficient
      expression of tagged snoRNAs in transgenic parasites opens the possibility of
      engineering novel methylation sites on different target RNAs in vivo.

PMID- 10909420
TI  - Gene therapy for T cell-mediated autoimmunity: teaching the immune system how to
      restrain its own harmful activities by targeted DNA vaccines.
AB  - We recently used a modification of gene therapy (naked DNA vaccination) to induce
      immunological memory against self-pro-inflammatory chemokines such as macrophage
      inflammatory protein-1 alpha or monocyte chemoattractant protein-1, and against
      the pro-inflammatory cytokine tumor necrosis factor-alpha. First, DNA constructs
      encoding each of the different pro-inflammatory mediators together with a
      repeated immunostimulatory sequence were prepared. Then, experiment animals were
      subjected to a repeated administration of each construct. Under these conditions,
      tolerance to the product of each insert was broken, and immunological memory
      established. Upon induction of experimental autoimmune encephalomyelitis, a T
      cell-mediated autoimmune disease of the central nervous system that serves as a
      model for multiple sclerosis or adjuvant induced arthritis, this memory was
      "turned on" to provide DNA-vaccinated animals a high state of disease resistance.
      Antibodies to the product of each inserted gene were isolated form these animals.
      Each antibody was found capable of neutralizing in vitro the chemoattractive
      properties of each relevant chemokine, thereby transferring disease resistance.
      Interestingly, the level of their production was dependent on disease severity,
      that is, each titer was accelerated in accordance with disease progression. Thus,
      by using a simple gene therapy technique the immune system could be "re-educated"
      to restrain its own harmful activities.

PMID- 10909421
TI  - Inhibitors of tyrosine kinases in the treatment of psoriasis.

PMID- 10909422
TI  - Non-peptidic analogs of the cell adhesion motif RGD prevent experimental liver
      injury.
AB  - In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholestatic
      liver diseases, T lymphocytes serve as effector cells of the immunostimulatory
      processes. Cellular interactions of immune cells with extracellular matrix
      components are regulated primarily via the beta 1 subfamily of integrin
      receptors. The target epitope of several such integrin receptors is the Arg-Gly
      Asp sequence, a cell adhesion motif shared by several matrix-associated adhesive
      glycoproteins. We review the use of synthetic non-peptidic analogs of RGD in the
      prevention of immune-mediated, concanavalin A-induced liver damage in mice and in
      inhibiting the development of liver cirrhosis in rats. The Con A-induced
      elevation of serum transaminases and tumor necrosis factor-alpha and the
      infiltration of liver tissue by inflammatory cells were inhibited by pretreatment
      of the mice with the synthetic RGD mimetics. In rats, the progression of
      thioacetamide-induced liver cirrhosis was markedly inhibited by the co
      administration of the RGD mimetic SF-6,5. The compounds described here may be
      examined therapeutically for pathological conditions in the liver, manifested as
      necro-inflammation and fibrosis.

PMID- 10909423
TI  - Anti-sense approach to anticholinesterase therapeutics.
AB  - The acetylcholine-hydrolyzing enzyme, acetylcholinesterase, is the molecular
      target of approved drugs for Alzheimer's disease and myasthenia gravis. However,
      recent data implicate AChE splicing variants in the etiology of complex diseases
      such as AD and MG. Despite the large arsenal of anti-AChE drugs, therapeutic
      inhibitors are primarily targeted towards an active site shared by all variants.
      In contrast, anti-sense oligonucleotides attack unique mRNA sequences rather than
      tertiary protein structures. AS-ODNs thus offer a means to target gene expression
      in a highly discriminative manner using very low concentrations of drug. In light
      of the likely role(s) of specific AChE variants in various diseases affecting
      cholinergic neurotransmission, the potential contribution that anti-sense
      technology can make towards improved approaches to anti-AChE therapeutics
      deserves serious attention.

PMID- 10909424
TI  - G proteins as a biochemical tool for diagnosis and monitoring treatments of
      mental disorders.
AB  - There is a significant gap between advances in medication for mental disorders
      and the present static situation of diagnosis and monitoring treatments of these
      disorders. Heterotrimeric G proteins play a pivotal role in postreceptor
      information transduction. These proteins were previously implicated by us in the
      biochemical mechanism underlying lithium action, and in the pathophysiology of
      mood disorders. We aimed at quantitatively and functionally evaluating G proteins
      in patients with major mental disorders in an attempt to unravel a differential
      pattern of G protein measures characterizing each disorder. We undertook G
      protein functional measurements coupled to beta-adrenergic, muscarinic or
      dopamine receptors through bacterial toxin-sensitive, agonist-enhanced [3H]
      Gpp(NH)p binding capacity, substituted by quantitative measures of G alpha s, G
      alpha i, and G beta subunit proteins through immunoblot analysis using polyclonal
      anti-G submit antibodies in mononuclear leukocytes obtained from patients with
      major mental disorders in comparison with healthy volunteers. A differential
      pattern of receptor coupled G protein function and of their immunoreactive levels
      were detected in mononuclear leukocytes of patient s for the following mental
      disorders: mania, depression, schizophrenia, and panic. Normalization of altered
      G protein measures in mood-disorder ed patients occurred under specific
      treatments. As state-dependent markers, G protein measures can potentially be
      used as an aid in both the biochemical diagnosis of mental disorders and in the
      biochemical monitoring of the response to a specific treatment.

PMID- 10909426
TI  - European Society of Anaesthesiologists 8th annual meeting with the Austrian
      International Congress. Vienna, Austria, 1-4 April 2000. Abstracts.

PMID- 10909425
TI  - 2-Thioether-5'-O-(1-thiotriphosphate)-adenosine derivatives: new insulin
      secretagogues acting through P2Y-receptors.
AB  - P2-receptors (P2-Rs) represent significant targets for novel drug development. P2
      Rs were identified also on pancreatic B cells and are involved in insulin
      secretion. The aim of our study was to synthesize and evaluate pharmacologically
      the novel P2Y-R ligands, 2-thioether-5'-O-phosphorothioate adenosine derivatives,
      as potential insulin secretagogues. An efficient synthesis of these nucleosides
      and a facile method for separation of the chiral products is described. The
      enzymatic stability of the compounds towards pig-pancreas NTPDase was evaluated.
      The rate of hydrolysis of 2-hexylthio-5'-O-(1-thiotriphosphate)-adenosine (2
      hexylthio-ATP-alpha-S) isomers by NTPDase was 28% that of ATP. The apparent
      affinity of the compounds to P2Y1-R was determined by measurement of P2Y-receptor
      promoted phospholipase C activity in turkey erythrocyte membranes. 2-RS-ATP-alpha
      S derivatives were agonists, stimulating the production of inositol phosphates
      with K0.5 values in the nM range. 2-RS-AMP-S derivatives were full agonists
      although 2 orders of magnitude less potent. All the compounds were more potent
      than ATP. The effect on insulin secretion and pancreatic flow rate was evaluated
      on isolated and perfused rat pancreas. A high increase, up to 500%, in glucose
      induced insulin secretion was due to addition of 2-hexylthio-ATP-alpha-S in the
      nM concentration range, which represents 100-fold enhancement of activity
      relative to ATP. 2-Hexylthio-AMP-S was 2.5 orders of magnitude less effective. A
      high chemical hydrolytic stability was observed for 2-hexylthio-ATP-alpha-S.
      Hydrolysis of the phosphoester bond, which was the only detectable degrading
      reaction under the investigation conditions (pH 7.4, 37 degrees C), was slow,
      with a half-life of 264 hours. Moreover, even at gastric juice conditions (pH
      1.4, 37 degrees C), hydrolysis of the terminal phosphate was the only detectable
      reaction, with a half-life of 17.5 hours. 2-Hexylthio-ATP-alpha-S isomers are
      enzymatically and chemically stable. These isomers are highly potent and
      effective insulin secretagogues, increasing, however, pancreatic vascular
      resistance.

PMID- 10909427
TI  - American Association for Cancer Education 32nd annual meeting. Portland, Oregon,
      USA. November 5-8, 1998. Abstracts.

PMID- 10909428
TI  - Mitosis and apoptosis in the pituitary gland: tumour formation or hyperplasia?
AB  - Direct analyses of trophic activity in the pituitary have been hampered by the
      lack of normal human tissue to study and by the short duration of the
      histologically overt phases of mitosis and apoptosis, which renders significant
      trophic events difficult to quantify. In rats and dogs, pituitary cell turnover
      is rapid in youth, declines markedly with age and virtually ceases by 'late
      middle age'. Specific stimuli superimpose brief but dramatic trophic events on
      this active background. There is little convincing evidence, as yet, for
      plasticity, i.e. the persistence of cell population changes after transient
      stimuli have passed. In contrast to spontaneous pituitary adenomas in rats, human
      pituitary tumours show relatively modest increases in mitotic activity. In the
      light of these observations, this chapter examines the accepted models of
      pituitary adenoma formation and propagation, with special reference to trophic
      activity, clonality and tumour behaviour.

PMID- 10909429
TI  - Pituitary tumour transforming gene: a novel factor in pituitary tumour formation.
AB  - Although pituitary tumours are common monoclonal neoplasms, they rarely
      metastasize outside the pituitary fossa, even though they cause considerable
      morbidity and mortality. Many molecular events underlying pituitary
      tumourigenesis have been elucidated in recent years, but no clear tumour marker
      has emerged that assists clinical decision-making with regard to appropriate
      therapy. Activating mutations and a loss of inactivating mutations, together with
      hypothalamic hormones, circulating hormones, growth factors and cytokines, co
      operatively ensure the inexorable expansion of the initial mutated pituitary cell
      clone. We have recently described a novel oestrogen-regulated activating
      oncogene, pituitary tumour transforming gene (PTTG), which is potently
      transforming in vitro and in vivo, regulates basic fibroblast growth factor
      secretion and inhibits chromatid separation. In experimental animal pituitary
      tumour models, increased PTTG expression occurs early in cell transformation
      (from normal to hyperplastic cell), PTTG overexpression being observed in 99% of
      pituitary tumours. PTTG presents an attractive target for designing subcellular
      pituitary tumour therapy, and an increased understanding of its role and that of
      other genetic events in pituitary tumorigenesis may provide novel approaches to
      pituitary tumour management.

PMID- 10909430
TI  - Tumour suppressor genes in pituitary tumour formation.
AB  - Studies of the molecular changes that characterize pituitary tumours have gone
      some way towards increasing our understanding of the events responsible for their
      initiation and progression. Allelic deletions on chromosomes 10, 11 and 13 are
      significantly associated with invasive and metastatic tumours, while losses on 9p
      occur early in pituitary tumorigenesis. Studies of known tumour suppressor genes
      within these regions of loss suggest a limited role, if any, in pituitary
      tumours. However, a loss of pRB is evident in a proportion of somatotrophinomas.
      Loss of p16 protein expression is associated with methylation of this gene's CpG
      island and is an early change in non-functional tumours. The enforced expression
      of p16/CDKN2A in the AtT20 cell line has shown that it is responsible for G1
      arrest, mimicking its in vivo role. Methylation may provide a unifying mechanism
      preceding and predisposing towards allelic loss, and in other cases leading to
      reduced tumour suppressor gene expression. Pharmacological interventions designed
      to induce the re-expression of genes silenced through this mechanism offer
      considerable therapeutic potential.

PMID- 10909431
TI  - Clinical management of prolactinomas.
AB  - Prolactinomas are benign, sporadic pituitary tumours that typically present with
      amenorrhoea and galactorrhoea in women, and hypogonadism and space-occupying
      effects in men. Hyperprolactinaemic hypogonadism in either sex is associated with
      reduced bone mineral density, which may be progressive and only partially
      reversible. For most microprolactinomas, dopamine agonists are the treatment of
      choice, achieving normoprolactinaemia and restoring gonadal function in 80-90% of
      cases. Trans-sphenoidal surgery is curative in 60%, but may be complicated by
      hypopituitarism and is usually reserved for patients with dopamine agonist
      intolerance or resistance. A subgroup of patients with small tumours, mild
      symptoms and normal gonadal function may be monitored without specific treatment-
      the risk of tumour expansion is small. Macroprolactinomas should be treated
      medically, dopamine agonists controlling prolactin secretion and achieving
      significant tumour shrinkage in 80% of cases, whereas surgery is curative in only
      a quarter. Cabergoline is the dopamine agonist of choice in most situations,
      being better tolerated and more effective than bromocriptine. Quinagolide is an
      effective alternative. Dopamine agonist withdrawal or dose reduction should be
      considered after 2-5 years therapy. Oestrogens may be used with caution in women
      with prolactinomas.

PMID- 10909432
TI  - The future of somatostatin analogue therapy.
AB  - Since its discovery almost 30 years ago, the mode of action and therapeutic
      applications of somatostatin have been defined. In particular the cloning and
      characterization of somatostatin receptor subtypes has facilitated the
      development of high affinity analogues. In the context of pituitary disease, long
      acting somatostatin analogues (octreotide, lanreotide) have been used to treat a
      variety of pituitary tumours but are most efficacious for the treatment of GH and
      TSH-secreting adenomas. In patients with acromegaly, depot preparations of these
      analogues are administered intramuscularly every 10-28 days and provide
      consistent suppression of GH levels to < 5 mU/l in approximately 50-65% of all
      cases. Even more specific somatostatin receptor analogues are under development.
      Finally, radiolabelled somatostatin analogue scintigraphy and, in larger doses,
      therapy, are now established tools in the evaluation and treatment of
      neuroendocrine tumours.

PMID- 10909433
TI  - Growth hormone receptor antagonists therapy for acromegaly.
AB  - Knowledge of the interaction between growth hormone (GH) and the growth hormone
      receptor (GHR) has led to the rational design of a GHR antagonist. An analogue of
      GH able to block the action of GH at the cellular level offers greater
      specificity of effect compared with current medical therapies and is not
      dependent on tumour characteristics. This chapter reviews the interaction between
      GH and the GHR, and discusses the outstanding issues regarding GHR antagonist
      therapy in acromegaly.

PMID- 10909434
TI  - Recent developments in gene therapy: applications for the treatment of pituitary
      tumours.
AB  - Pituitary tumours are normally benign, highly differentiated and slow growing
      neoplasms. Nevertheless, as many as half of them will show evidence of local
      invasion into the surrounding structures. Despite their benign growth
      characteristics and slow clinical progression, pituitary tumours commonly cause
      serious morbidity. The mass effects of large tumours, including headache and
      visual failure from optic chiasm compression, may cause lifelong disability.
      Hormone hypersecretion or deficiency causes major clinical problems that often
      require expensive and long-term medical therapy. Major advances have been made in
      the therapy of pituitary tumours over the past 20-30 years, but despite this,
      their treatment often remains an unsatisfactory compromise in practice. There is,
      therefore, a place for improvements in therapy, and to this end, gene therapy may
      come to hold a significant place in the future treatment of human pituitary
      tumours. With the development of new gene delivery vehicles, this concept can now
      be explored with a view to treating specific types of pituitary tumours.

PMID- 10909435
TI  - Sporadic pituitary tumours: from epidemiology to use of databases.
AB  - Pituitary tumours account for 10% of intracranial neoplasms and have an annual
      incidence of about 25 per million head of population. Prolactinomas and non
      functioning tumours are the most common subtypes clinically, as well as in
      surgical and histopathological series. In pre-pubertal children,
      corticotrophinomas, although rare, are the most common subtype, prolactinomas
      being most common in adolescents. In autopsy series, 11% of pituitaries harbour
      an adenoma. These are usually small (less than 10 mm in diameter), and where
      examined, about half are prolactinomas. Computed tomography or magnetic resonance
      imaging examination of normal subjects reveals abnormalities of greater than 3 mm
      in diameter in 10% of pituitaries. Other cancers in patients with pituitary
      tumours are confined to acromegalics, in whom colonic lesions are more prevalent
      than in the general population. Several long-term sequelae of pituitary tumours
      with respect to morbidity and mortality have been identified from retrospective
      analyses. However, data on these are not standardized, requiring the development
      of national databases and registers to collect clinical outcomes from large
      cohorts according to agreed standard proformas. These registers will provide a
      sufficient number of cases for statistically valid conclusions on different
      clinical subgroups. The development of national guidelines for best practice for
      the management of patients with these tumours provides the basis for an audit of
      the management process and outcomes between centres. This will inform decisions
      on the optimum configuration of services for such patients.

PMID- 10909436
TI  - Gamma knife radiosurgery for pituitary tumours.
AB  - Stereotactic radiosurgery with the gamma knife delivers focused radiation from a
      cobalt-60 source in a single session to a pituitary tumour with minimal radiation
      to the adjacent normal brain tissue. Currently, gamma knife radiosurgery is
      predominantly used to treat failed pituitary surgery, although it has a role as a
      primary treatment for patients unwilling or unsuitable, for medical reasons, to
      undergo trans-sphenoidal surgery. The major risk from gamma knife radiosurgery is
      radiation damage to the visual pathways, but this can be avoided by limiting the
      radiation dose to the optic chiasm to under 10 Gy. In contrast, the neuronal and
      vascular structures running in the cavernous sinus are much less radiosensitive,
      allowing an ablative dose to be administered to tumours showing lateral invasion
      and impinging on cranial nerves III, IV, V and VI. Gamma knife radiosurgery
      appears to produce remission in secretory tumours faster than fractionated
      radiotherapy. Furthermore, the potential long-term risk of developing a second
      extra-pituitary brain tumour, as well as the neuropsychiatric effects associated
      with conventional radiation administration, seems less likely to occur with this
      form of treatment.

PMID- 10909437
TI  - New developments in pituitary surgical techniques.
AB  - Despite ongoing advances in the pharmacological, radiotherapeutic and endocrine
      management of pituitary tumours, surgery remains the therapy of choice for the
      large majority of these lesions. As surgical efficacy is now being judged by more
      rigorous technical standards and by more stringent endocrine criteria than ever
      before, such scrutiny has only served to reinforce the fundamental role of
      surgery in pituitary tumour management. With the revival of the trans-sphenoidal
      approach, together with its ongoing technical evolution during the past three
      decades, pituitary tumours have emerged as eminently treatable lesions, with
      trans-sphenoidal microsurgery affording long-term, high-quality survival in many
      patients. Pituitary surgery is, however, not without limitation or liability.
      Even in experienced hands, endocrine and/or oncological remission is not
      uniformly achieved. Moreover, of those patients in whom such 'cures' can be
      induced, the durability of the response is not absolute, as tumour recurrence
      will continue to threaten a small but significant proportion of patients over
      time. Finally, and notwithstanding the fact that trans-sphenoidal surgery remains
      one of the safest procedures in contemporary, neurosurgical practice,
      complications can occur, some of which can be associated with significant
      morbidity and, on rare occasions, mortality. Clearly, there continue to be areas
      in need of improvement, and it has been in response to these limitations of
      contemporary pituitary surgery that neurosurgeons have sought to develop
      alternative strategies to improve surgical outcome. As a result, a variety of
      important innovations have been introduced during recent years. Among others, the
      most important and effective of these have been the application of
      neuronavigational techniques, trans-sphenoidal endoscopy and intraoperative MR
      resection control to the standard trans-sphenoidal approach to pituitary tumours.
      Whereas some advances are conceptual and others are technical, all are helping to
      push the limits of pituitary surgery to new frontiers of efficacy and safety. In
      this chapter, the current state of the art of pituitary surgery is reviewed along
      with those important new developments that, in the foreseeable future, hope to
      improve the quality of surgical care available to the pituitary tumour patient.

PMID- 10909438
TI  - Shedding light on induced molting.

PMID- 10909439
TI  - HOD will decide 'wether' to adopt lamb tail docking position.

PMID- 10909440
TI  - Views on laws governing dog ownership by breed.

PMID- 10909441
TI  - What is your diagnosis? Cataract, retinal detachment, and a large mass protruding
      into the vitreous cavity.

PMID- 10909442
TI  - What discipline can veterinary licensing boards impose?

PMID- 10909443
TI  - Viremia, virus shedding, and antibody response during natural avian polyomavirus
      infection in parrots.
AB  - OBJECTIVE: To determine rapidity of spread and onset and duration of viremia,
      virus shedding, and antibody production in parrots naturally infected with avian
      polyomavirus (APV). DESIGN: Case series. ANIMALS: 92 parrots in 2 aviaries.
      PROCEDURE: Blood samples were obtained from parrots naturally exposed to APV
      during a 3- to 4-month period for determination of serum virus neutralizing
      antibody and detection of viral DNA. Nestlings from the next year's hatch were
      monitored for APV infection. RESULTS: The first indication of inapparent
      infection was viremia, which developed simultaneously with or was followed within
      1 week by cloacal virus shedding and antibody production. Cloacal virus shedding
      continued after viremia ceased. During viremia, viral DNA was detected
      continuously in blood samples. Viral DNA was detected in serial cloacal swab
      specimens in most birds, but it was detected inconsistently in 6 birds and not
      detected in 3 birds, even though these birds were viremic. Duration of cloacal
      virus shedding was < or = 4.5 months. In 1 aviary, prevalence of infection was
      88% and dissemination of virus through the 3-room building required 4.5 months.
      In the second aviary, a single-room nursery, prevalence of infection was > or =
      90%. For all affected birds, infection could be detected 18 days after the first
      death. CONCLUSIONS AND CLINICAL RELEVANCE: If a single sampling is used for
      polymerase chain reaction detection of viral DNA, blood and cloacal swab
      specimens are required. In nestling nonbudgerigar parrots, cloacal virus shedding
      may persist for 4.5 months. Management protocols alone are sufficient to prevent
      introduction of APV into a nursery.

PMID- 10909444
TI  - Evaluation of serum feline trypsin-like immunoreactivity for the diagnosis of
      pancreatitis in cats.
AB  - OBJECTIVE: To evaluate serum feline trypsin-like immunoreactivity (fTLI)
      concentration and results of abdominal ultrasonography, CBC, and serum
      biochemical analyses for diagnosis of pancreatitis in cats. DESIGN: Prospective
      study. ANIMALS: 28 cats with clinical signs compatible with pancreatitis.
      PROCEDURE: Serum fTLI concentrations were determined, and abdominal
      ultrasonography, CBC, and serum biochemical analyses were performed prior to
      histologic evaluation of pancreatic, hepatic, and intestinal specimens. On the
      basis of histologic results, cats were categorized as having a normal pancreas (n
      = 10), pancreatic fibrosis with ongoing inflammation (9), pancreatic fibrosis
      without inflammation (4), and acute necrotizing pancreatitis (5). Serum fTLI
      concentrations and results of CBC, serum biochemical analyses, and histologic
      evaluation of hepatic and intestinal specimens were compared among groups.
      RESULTS: Significant differences in serum fTLI concentrations or any hematologic
      or biochemical variable were not detected among the 4 groups of cats. Median
      serum fTLI concentrations were 51 micrograms/L (range, 18 to 200 micrograms/L) in
      cats with a normal pancreas, 32 micrograms/L (range, 12 to > 200 micrograms/L) in
      cats with pancreatic fibrosis and ongoing inflammation, 124 micrograms/L (range,
      36 to > 200 micrograms/L) in cats with pancreatic fibrosis without ongoing
      inflammation, and 30 micrograms/L (range, 24 to 84 micrograms/L) in cats with
      acute necrotizing pancreatitis. We detected a high prevalence of concurrent
      hepatic and intestinal tract disease in cats with pancreatitis. CONCLUSIONS AND
      CLINICAL RELEVANCE: In cats with clinical signs of pancreatitis, serum fTLI
      concentration is poorly associated with histopathologic diagnosis.

PMID- 10909445
TI  - Use of physiatry as the sole treatment for three paretic or paralyzed dogs with
      chronic compressive conditions of the caudal portion of the cervical spinal cord.
AB  - Physiatry alone was used to treat 3 large (30- to 40-kg [66 to 88 lb]) mature (6-
      to 9-year-old) dogs that were tetraparetic or tetraplegic. All 3 dogs had
      myelographic evidence of multiple chronic compressive extradural lesions of the
      caudal portion of the cervical spinal cord. All dogs improved substantially after
      a course of intensive physical treatment. For 2 dogs, an abbreviated treatment
      regimen was continued by the owners after the dogs were discharged. Both of these
      dogs regained and retained normal neurologic function. The other dog improved but
      was treated infrequently at home. That dog's signs recurred, and the dog was
      euthanatized. Persistent use of physical treatment for paralysis that results
      from conditions affecting the cervical spinal cord may be useful even without
      concurrent surgical or pharmacologic treatments.

PMID- 10909446
TI  - Reliability of history and physical examination findings for assessing control of
      glycemia in dogs with diabetes mellitus: 53 cases (1995-1998).
AB  - OBJECTIVE: To evaluate the reliability of history and physical examination
      findings for assessing control of glycemia in insulin-treated diabetic dogs.
      DESIGN: Retrospective study. ANIMALS: 53 insulin-treated dogs with diabetes
      mellitus. PROCEDURE: Medical records of insulin-treated diabetic dogs from June
      1995 to June 1998 were reviewed, and information on owner perception of their
      dog's response to insulin treatment, physical examination findings, body weight,
      insulin dosage, and concentrations of food-withheld (i.e., fasting) blood glucose
      (FBG), mean blood glucose (MBG) during an 8-hour period, blood glycosylated
      hemoglobin (GHb), and serum fructosamine was obtained. Owner's perception of
      their dog's response to insulin treatment, physical examination findings, and
      changes in body weight were used to classify control of glycemia as good or poor
      for each dog. The FBG, MBG/8 h, blood GHb, and serum fructosamine concentrations
      were compared between well-controlled and poorly controlled insulin-treated
      diabetic dogs. RESULTS: Presence or absence of polyuria, polydipsia, polyphagia,
      lethargy, and weakness were most helpful in classifying control of glycemia. Mean
      FBG and MBG/8 h concentrations, blood GHb concentrations, and serum fructosamine
      concentrations were significantly decreased in 25 well-controlled diabetic dogs,
      compared with 28 poorly controlled diabetic dogs. Most well-controlled diabetic
      dogs had concentrations of FBG between 100 and 300 mg/dl, MBG/8 h < or = 250
      mg/dl, blood GHb < or = 7.5%, and serum fructosamine < or = 525 mumol/L, whereas
      most poorly controlled diabetic dogs had results that were greater than these
      values. CONCLUSIONS AND CLINICAL RELEVANCE: Reliance on history, physical
      examination findings, and changes in body weight are effective for initially
      assessing control of glycemia in insulin-treated diabetic dogs.

PMID- 10909447
TI  - Differences in total protein concentration, nucleated cell count, and red blood
      cell count among sequential samples of cerebrospinal fluid from horses.
AB  - OBJECTIVE: To examine total protein concentration and cell counts of sequentially
      collected samples of CSF to determine whether blood contamination decreases in
      subsequent samples and whether formulas used to correct nucleated cell count and
      total protein concentration are accurate. DESIGN: Case series. ANIMALS: 22
      horses. PROCEDURE: For each horse, 3 or 4 sequential 2-ml samples of CSF were
      collected from the subarachnoid space in the lumbosacral region into separate
      syringes, and blood was obtained from the jugular vein. Total protein
      concentration, nucleated cell count, and RBC counts were determined in all
      samples. RESULTS: Among 3 sequential samples, total protein concentration and RBC
      count were significantly lower in samples 2 and 3, compared with sample 1.
      Nucleated cell count was significantly lower in sample 3, compared with sample 1.
      Among 4 sequential samples, total protein concentration and RBC count were
      significantly lower in samples 2, 3, and 4, compared with sample 1. Nucleated
      cell count was significantly lower in samples 3 and 4, compared with sample 1.
      For 3 correction formulas, significant differences in corrected values for
      nucleated cell count and total protein concentration were detected between sample
      1 and sample 3 or 4. CONCLUSIONS AND CLINICAL RELEVANCE: Because iatrogenic blood
      contamination decreases in sequential CSF samples, a minimum of 3 samples should
      be collected before submitting the final sample for analysis. Formulas to correct
      nucleated cell count and total protein concentration are inaccurate and should
      not be used to correct for blood contamination in CSF samples.

PMID- 10909448
TI  - Diagnosis and management of abnormal embryonic development characterized by
      formation of an embryonic vesicle without an embryo in mares.
AB  - OBJECTIVE: To determine the incidence, ultrasonographic characteristics, and risk
      factors associated with embryonic development characterized by formation of an
      embryonic vesicle without an embryo in mares. DESIGN: Prevalence survey. ANIMALS:
      159 pregnant mares. PROCEDURES: From 1994 to 1998, mares between 11 and 40 days
      after ovulation with normal and abnormal embryonic development were examined
      ultrasonographically, and characteristics of each conceptus were recorded.
      RESULTS: The incidence of abnormal embryonic development in mares characterized
      by formation of an embryonic vesicle without an embryo was 7/159 (4.4%) during
      the 5 breeding seasons. Age and breed of mare or type of semen used did not
      differ for mares with normal and abnormal embryonic development. The percentage
      of mares in which the conceptus was undersized during > or = 1 examination was
      significantly higher for mares with abnormal conceptuses (5/7), compared with
      mares with normal conceptuses (2/147; 1.4%). The percentage of examinations
      during which the conceptus was undersized was significantly higher for abnormal
      conceptuses (12/27; 44.4%), compared with normal conceptuses (4/448; 0.9%).
      CONCLUSIONS AND CLINICAL RELEVANCE: To diagnose an embryonic vesicle without an
      embryo, mares should be examined by use of transrectal ultrasonography on day 25
      after ovulation. When an embryo cannot be identified at that time, mares should
      be reexamined at intervals of 1 to 3 days until day 30. Because undersized
      conceptuses are more likely to be abnormal, development of undersized conceptuses
      should be monitored closely.

PMID- 10909449
TI  - Streptococcal toxic shock in a horse.
AB  - A 14-year-old horse was admitted to the veterinary hospital for treatment of
      tachycardia and lethargy. Initial diagnoses were ventricular tachycardia and
      renal dysfunction. During hospitalization other findings included fever, renal
      failure, hepatic failure, hypotension, and intermittent ventricular arrhythmias.
      Bacteriologic culture of 2 blood samples collected during febrile crises 7 days
      apart yielded Streptococcus mitis. These culture results along with other
      clinical and physical examination findings fulfill the criteria for a diagnosis
      of streptococcal toxic shock syndrome, previously described for humans and dogs.
      To our knowledge this is the first reported instance of this disease in a horse.

PMID- 10909450
TI  - Risk of adverse effects in pneumonic foals treated with erythromycin versus other
      antibiotics: 143 cases (1986-1996).
AB  - OBJECTIVE: To determine whether foals with pneumonia that were treated with
      erythromycin, alone or in combination with rifampin or gentamicin, had a higher
      risk of developing adverse effects, compared with foals treated with trimethoprim
      sulfamethoxazole (TMS), penicillin G procaine (PGP), or a combination of TMS and
      PGP (control foals). DESIGN: Retrospective study. ANIMALS: 143 foals < 240 days
      old. PROCEDURE: Information on age, sex, breed, primary drug treatment, total
      days of treatment with the primary drug, and whether the foal developed diarrhea,
      hyperthermia, or respiratory distress was obtained from the medical records.
      Relative risk (RR) and attributable risk (AR) were calculated to compare risk of
      adverse reactions between foals treated with erythromycin and control foals.
      RESULTS: Only 3 (4.3%) control foals developed diarrhea; none developed
      hyperthermia or respiratory distress. Foals treated with erythromycin had an 8
      fold risk (RR, 8.3) of developing diarrhea, compared with control foals, and
      increased risks of hyperthermia (AR, 25%) and respiratory distress (AR, 15%).
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of erythromycin to
      treat foals with pneumonia was associated with an increased risk of diarrhea,
      hyperthermia, and respiratory distress, compared with use of TMS or PGP.

PMID- 10909451
TI  - Treatment of supraspinous bursitis by use of debridement in standing horses: 10
      cases (1968-1999).
AB  - OBJECTIVE: To evaluate efficacy of debridement for treatment of supraspinous
      bursitis in horses and to evaluate the outcome. DESIGN: Retrospective study.
      ANIMALS: 10 horses with clinical signs of supraspinous bursitis. PROCEDURE:
      Medical records were reviewed for signalment, anamnesis, results of physical and
      radiographic examination, microbial culture results of supraspinous bursa tissue
      or exudate, Brucella abortus titers, type of antimicrobial and anti-inflammatory
      therapies, surgical technique, complications of the surgical procedure, and
      findings on histologic examination of excised nuchal ligament and bursal tissue.
      Telephone follow-up with owners, trainers, or referring veterinarians was
      performed. RESULTS: The described surgical technique was effective in resolving
      drainage from the supraspinous bursal region in 5 of 6 horses available for long
      term follow-up. The most common complication following surgery was the
      development of purulent wound drainage. Two horses required multiple surgeries to
      resolve clinical signs of supraspinous bursitis. The most common organism
      isolated from the supraspinous bursa was beta-hemolytic Streptococcus spp. All
      horses were discharged from the hospital and long-term follow-up was available
      for 6 horses. All 6 horses could be used for their intended use. CONCLUSIONS AND
      CLINICAL RELEVANCE: Debridement in standing horses is an effective method of
      resolving clinical signs of supraspinous bursitis.

PMID- 10909452
TI  - Effect of split nursing on variation in pig growth from birth to weaning.
AB  - OBJECTIVE: To determine the effect of split nursing (i.e., removal of the larger
      pigs in a litter from the dam for a short period within 24 hours after birth to
      allow the smaller pigs in the litter uninhibited access to the dam) on variation
      in growth from birth to weaning among pigs. DESIGN: Clinical trial. ANIMALS:
      1,193 pigs in 118 litters. PROCEDURE: Litters were randomly assigned to 1 of 3
      treatment groups: control group (pigs were not split nursed), group 1 (heaviest
      50% of pigs in the litter were removed from the sow for 2 hours), or group 2
      (heaviest 50% of pigs were removed from the sow for 2 hours and, after the
      heaviest pigs were returned to the sow, the lightest 50% of pigs were removed for
      2 hours). Birth weights and weaning weights were measured. RESULTS: Significant
      differences in average daily gain (ADG), weaning weight, or serum IgG
      concentration among groups were not detected. However, significant linear
      improvements in the SD and coefficient of variation of the ADG were detected, but
      only for litters with > or = 9 pigs born alive. Percentages of pigs from split
      nursed litters that weighed < 3.6 kg (8 lb) at weaning (1.3 and 1.6% for groups 1
      and 2, respectively) were lower than percentage of control pigs that did (3%).
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that split nursing will
      decrease variation in ADG of pigs from birth to weaning but only for pigs from
      litters with > or = 9 pigs born alive.

PMID- 10909453
TI  - History, trends, and extent of pasteurization.

PMID- 10909454
TI  - What is your diagnosis? Acute pulmonary thromboembolism secondary to spontaneous
      death of adult heartworms.

PMID- 10909455
TI  - Theriogenology question of the month. An ectopic fetus.

PMID- 10909456
TI  - Biosecurity practices of beef cow-calf producers.
AB  - OBJECTIVE: To evaluate biosecurity practices of cow-calf producers. DESIGN: Cross
      sectional survey. SAMPLE POPULATION: 2,713 cow-calf operations were used in phase
      1 of the study, and 1,190 cow-calf operations were used in phase 2. PROCEDURE:
      Producers were contacted for a personal interview between Dec 30, 1996 and Feb 3,
      1997 regarding their management practices. Noninstitutional operations with 1 or
      more beef cows were eligible to participate in the study. Producers who
      participated in the first phase of the study and who had > or = 5 beef cows were
      requested to continue in the study and were contacted by a veterinarian or animal
      health technician who administered further questionnaires. All contacts for the
      second phase of the study were made between Mar 3, 1997 and Apr 30, 1997.
      Additional data on use of various vaccines, testing of imported cattle for
      brucellosis, Mycobacterium paratuberculosis, bovine viral diarrhea, and
      tuberculosis as well as potential for feed contamination were collected during
      the second phase of the study. RESULTS: Producers commonly engaged in management
      practices that increased risk of introducing disease to their cattle such as
      importing cattle, failing to quarantine imported cattle, and communal grazing.
      Producers inconsistently adjusted for the increased risk of their management
      practices by increasing the types of vaccines given, increasing the quarantine
      time or proportion of imported animals quarantined, or increasing testing for
      various diseases in imported animals. CONCLUSIONS AND CLINICAL RELEVANCE: Cow
      calf herds are at risk for disease exposure from outside sources when cattle are
      introduced to the herd, and producers do not always adjust management practices
      such as vaccination schedules and quarantine procedures appropriately to minimize
      this risk. Veterinary involvement in education of producers regarding biosecurity
      risks and development of rational and economical biosecurity plans is needed.

PMID- 10909457
TI  - Animal bite epidemiology and surveillance for rabies postexposure prophylaxis.
AB  - OBJECTIVES: To understand the epidemiology of animal bites and exposure, evaluate
      the animal exposure reporting system for surveillance of rabies postexposure
      prophylaxis (PEP), and identify opportunities to reduce PEP. DESIGN: Period
      prevalence survey. STUDY POPULATION: Pennsylvania residents in 1995. PROCEDURE:
      Data from animal bite reports from Pennsylvania county health offices were
      summarized for 1995. Animal bite incidences for the state, counties, various age
      groups, and various population densities were calculated. Animal species,
      treatment, location of wounds, and PEP recommendations were evaluated for
      exposures. RESULTS: More than 16,000 animal-related potential rabies exposures
      were reported from 65 of 67 counties in Pennsylvania. The highest incidence was
      in children less than 5 years old (324/100,000). Of the 75% of victims requiring
      wound treatment, 50% received antimicrobials, 29% received a tetanus toxoid, and
      19% had wounds sutured, were admitted to hospitals, or were referred for plastic
      surgery. Although 75% of exposures were to dogs, victims exposed to cats were 6
      times as likely to receive PEP (relative risk, 6.1; 95% confidence interval, 5.1
      to 7.4). Thirty percent of 556 PEP were given for exposures to dogs, 44% for
      cats, 7% for raccoons, 4% for bats, 2.5% for squirrels, 2.1% for groundhogs, 2%
      for foxes, and 8% for exposures to other species. Fifty-nine percent of owned
      dogs were up-to-date on rabies vaccinations compared with 41% of owned cats.
      CONCLUSION: Interventions, such as dog bite prevention education, vaccination of
      pets against rabies, appropriate use of PEP, and reduction of feral cat
      populations, should be instituted, enhanced, or better enforced in communities.

PMID- 10909458
TI  - Effect of timing of blood collection on serum phenobarbital concentrations in
      dogs with epilepsy.
AB  - OBJECTIVE: To determine whether there are therapeutically relevant changes in
      serum phenobarbital concentrations throughout a daily dosing interval in
      epileptic dogs receiving phenobarbital for > or = 3 weeks. DESIGN: Prospective
      study. ANIMALS: 33 epileptic dogs receiving phenobarbital. PROCEDURE: Serum
      phenobarbital concentrations were measured at 0 hour (trough), 3 hours, and 6
      hours after oral administration of phenobarbital in epileptic dogs that had
      received phenobarbital twice daily for a minimum of 3 weeks. For each dog,
      trough, 3-hour, and 6-hour serum phenobarbital concentrations were evaluated to
      determine whether they were within the same therapeutic category (lower, middle,
      or upper end of the therapeutic range of 15 to 45 micrograms/ml), or whether
      there was a > 30% change in serum concentrations throughout the day. RESULTS:
      Ninety-one percent (30/33) of dogs had trough, 3-hour, and 6-hour serum
      phenobarbital concentrations in the same therapeutic category. Only 9% (3/33) of
      dogs had trough, 3-hour, and 6-hour serum concentrations in different therapeutic
      categories with a > 30% change in concentrations throughout the day. Significant
      differences were not detected among mean serum phenobarbital concentrations when
      comparing the trough, 3-hour, and 6-hour samples for all dogs. CONCLUSIONS AND
      CLINICAL RELEVANCE: There is no therapeutically relevant change in serum
      phenobarbital concentrations throughout a daily dosing interval in most epileptic
      dogs. Therefore, timing is not important when collecting blood samples to measure
      serum phenobarbital concentrations in most epileptic dogs treated long-term with
      phenobarbital.

PMID- 10909459
TI  - Radiation treatment for incompletely resected soft-tissue sarcomas in dogs.
AB  - OBJECTIVE: To evaluate efficacy of radiation for treatment of incompletely
      resected soft-tissue sarcomas in dogs. DESIGN: Prospective serial study. ANIMALS:
      48 dogs with soft-tissue sarcomas. PROCEDURE: Tumors were resected to < 3 cm3
      prior to radiation. Tumors were treated on alternate days (three 3-Gy
      fractions/wk) until 21 fractions had been administered. Cobalt 60 radiation was
      used for all treatments. RESULTS: Five-year survival rate was 76%, and survival
      rate was not different among tumor types or locations. Four (8%) dogs developed
      metastases. Eight (17%) dogs had tumor recurrence after radiation. Development of
      metastases and local recurrence were significantly associated with reduced
      survival rate. Median survival time in dogs that developed metastases was 250
      days. Median disease-free interval for all dogs was 1,082 days. Median time to
      recurrence was 700 days. Dogs that developed recurrence after a prolonged period
      responded well to a second surgery. Acute radiation toxicosis was minimal;
      osteosarcoma developed at the radiation site in 1 dog. CONCLUSIONS AND CLINICAL
      RELEVANCE: An excellent long-term survival rate may be achieved by treating soft
      tissue sarcomas in dogs with resection followed by radiation. Amputation is not
      necessary for long-term control of soft-tissue sarcomas in limbs. Development of
      metastases and recurrence of local tumors after radiation treatment are
      associated with decreased survival rate. Acute and delayed radiation toxicosis
      was minimal with the protocol used in this study.

PMID- 10909460
TI  - Prevalence of Dirofilaria immitis infection among shelter cats.
AB  - OBJECTIVE: To determine prevalence of Dirofilaria immitis infection among shelter
      cats. DESIGN: Cross-sectional study. ANIMALS: 239 cats euthanatized at an animal
      shelter in southeastern Michigan. PROCEDURE: A gross necropsy focusing on the
      thoracic cavity, heart, lungs, and pulmonary vessels was performed within 5 hours
      after cats were euthanatized. Blood was collected directly from the heart of cats
      found to be infected and tested, using a filter test for microfilariae. Serum was
      tested for D immitis antigens by use of 2 antigen detection kits and for D
      immitis-specific antibodies by use of 2 antibody detection kits. RESULTS: Cats
      ranged from approximately 4 months to 15 years old. Adult D immitis were found in
      6 (2.5%) cats. Blood could not be recovered from 1 of the cats with heartworm
      infection. For the 5 other cats, results of the filter test were negative, and
      results of both antigen and both antibody tests were positive. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggest that cats living in an urban area in the
      northern part of the United States have a low prevalence of adult D immitis
      infection. However, this is likely to be an underestimate of the true prevalence
      of infection, because no attempts were made to identify cats infected with larval
      or juvenile stages of D immitis.

PMID- 10909461
TI  - Use of abdominal ultrasonography in the diagnosis of primary hyperaldosteronism
      in a cat.
AB  - A 13-year-old castrated male cat was examined because of a 2-week history of
      weakness, cervical ventroflexion, and dysphagia. Clinicopathologic abnormalities
      included hypokalemia and high serum creatine kinase activity. Abdominal
      ultrasonography revealed a 15-mm spherical mass in the area of the left adrenal
      gland. Plasma aldosterone concentration was high, and plasma renin activity was
      low. Findings were diagnostic of primary hyperaldosteronism. The cat responded
      well to intravenous and oral potassium supplementation while in the hospital. The
      owner declined surgery; therefore, repeated follow-up abdominal ultrasonography
      was recommended. The cat did well clinically with medical management alone until
      day 334, when it was lost to follow-up.

PMID- 10909462
TI  - Eclampsia in dogs: 31 cases (1995-1998).
AB  - OBJECTIVE: To compare clinical characteristics and laboratory findings of dogs
      with eclampsia with those of dogs without eclampsia. DESIGN: Retrospective study.
      ANIMALS: 31 dogs with eclampsia (affected) and 31 with dystocia (controls).
      PROCEDURE: Information on signalment, type of diet, reproductive history, litter
      size, time from whelping to eclampsia, body weight, clinical signs, results of
      physical examination and hematologic and biochemical analyses, response to
      calcium supplementation, and recurrence was obtained from the medical records of
      all dogs with eclampsia evaluated between 1995 and 1998 and compared with
      information from medical records of 31 of 102 dogs with dystocia evaluated during
      the same period. RESULTS: Dogs with eclampsia weighed less, had a smaller body
      weight-to-litter size ratio, higher rectal temperature and heart and respiratory
      rates, and lower plasma total solids concentration than control dogs. Ionized
      calcium concentration was < or = 0.8 mmol/L for all but 1 of the affected dogs;
      median concentration for the affected dogs was significantly less than that for
      control dogs. Six (19%) dogs did not manifest typical clinical signs associated
      with eclampsia. Twelve (39%) dogs with eclampsia had previous litters; none had a
      history of eclampsia. Affected dogs were discharged from the hospital within
      hours after admission, but 3 dogs returned 1 to 3 weeks later because of
      recurrence of eclampsia. CONCLUSIONS AND CLINICAL RELEVANCE: Eclampsia develops
      primarily in small-breed dogs with large litters. Plasma ionized calcium
      concentrations > 0.8 mmol/L in dogs with clinical signs typical of hypocalcemia
      may indicate that other causes of clinical signs should be considered. In
      addition, some dogs with eclampsia may have low ionized calcium concentrations
      and not manifest typical clinical signs.

PMID- 10909463
TI  - Association of disease with isolation and virulence of Rhodococcus equi from farm
      soil and foals with pneumonia.
AB  - OBJECTIVE: To determine whether isolation and virulence of Rhodococcus equi from
      soil and infected foals are associated with clinical disease. DESIGN: Cross
      sectional and case-control study. SAMPLE POPULATION: R equi isolates from 50
      foals with pneumonia and soil samples from 33 farms with and 33 farms without a
      history of R equi infection (affected and control, respectively). PROCEDURE: R
      equi was selectively isolated from soil samples. Soil and clinical isolates were
      evaluated for virulence-associated protein antigen plasmids (VapA-P) and
      resistance to the beta-lactam antibiotics penicillin G and cephalothin.
      Microbiologic cultures and VapA-P assays were performed at 2 independent
      laboratories. RESULTS: VapA-P was detected in 49 of 50 (98%) clinical isolates;
      there was complete agreement between laboratories. Rhodococcus equi was isolated
      from soil on 28 of 33 (84.8%) affected farms and 24 of 33 (72.7%) control farms,
      but there was poor agreement between laboratories. Virulence-associated protein
      antigen plasmids were detected on 14 of 66 (21.2%) farms by either laboratory,
      but results agreed for only 1 of the 14 VapA-P-positive farms. We did not detect
      significant associations between disease status and isolation of R equi from
      soil, detection of VapA-P in soil isolates, or resistance of soil isolates to
      beta-lactam antibiotics. No association between beta-lactam antibiotic resistance
      and presence of VapA-P was detected. CONCLUSIONS AND CLINICAL RELEVANCE: On the
      basis of soil microbiologic culture and VapA-P assay results, it is not possible
      to determine whether foals on a given farm are at increased risk of developing
      disease caused by R equi.

PMID- 10909464
TI  - Fecal shedding of Salmonella spp by horses in the United States during 1998 and
      1999 and detection of Salmonella spp in grain and concentrate sources on equine
      operations.
AB  - OBJECTIVE: To estimate prevalence of fecal shedding of Salmonella spp among
      horses in the US horse population and prevalence of Salmonella spp in grain or
      other concentrate used as horse feed on equine operations in the United States.
      DESIGN: Cross-sectional survey. SAMPLE POPULATION: Horses on 972 operations in 28
      states. PROCEDURE: Fecal samples were collected from horses resident at each
      operation. Only a single sample was collected from any individual horse; number
      of horses from which samples were collected on each operation was determined on
      the basis of number of horses on the operation. A single sample of grain or
      concentrate was also collected from each operation. All samples were tested for
      Salmonella spp by means of bacterial culture. RESULTS: Overall, 0.8% (SE, 0.5) of
      resident horses shed Salmonella spp in their feces. The overall prevalence of
      operations positive for fecal shedding of Salmonella spp (i.e., operations with >
      or = 1 horse shedding Salmonella spp in its feces) was 1.8% (SE, 0.7). Prevalence
      of grain or other concentrate samples positive for Salmonella spp was 0.4%.
      Serotypes of Salmonella spp that were identified in grain or other concentrate
      were not those typically associated with clinical disease in horses. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results suggest that the national prevalence of fecal
      shedding of Salmonella spp by horses in the United States was 0.8%, and that
      prevalence of Salmonella spp in grain or other concentrate used for horse feed
      was 0.4%.

PMID- 10909465
TI  - Concentration of cardiac troponin I in a horse with a ruptured aortic
      regurgitation jet lesion and ventricular tachycardia.
AB  - An 18-year-old Thoroughbred gelding was evaluated because of sudden onset of
      ventricular tachycardia and signs of colic. Three years earlier, a diastolic
      decrescendo murmur, consistent with aortic regurgitation, had been detected, but
      the horse continued to perform well and compete successfully. Cardiac
      ultrasonographic examination revealed a defect in the interventricular septum
      below the aortic root, and serum concentrations of cardiac troponin I (cTnI) were
      higher than those measured in clinically normal horses. Repeated development of
      tachyarrhythmia during hospitalization prompted a decision to euthanatize the
      horse. A ruptured endocardial jet lesion below the aortic valve with formation of
      a cleft into the interventricular septum was found on necropsy. This report of
      increased serum cTnI concentrations in a horse with myocardial disease and our
      other findings suggest that assessment of cardiac troponin concentrations may be
      a useful tool in the evaluation of horses with suspected myocardial disease.

PMID- 10909466
TI  - Arthroscopic removal of fracture fragments involving a portion of the base of the
      proximal sesamoid bone in horses: 26 cases (1984-1997).
AB  - OBJECTIVE: To determine the outcome of horses with basal fractures of the
      proximal sesamoid bone from which a fracture fragment involving a portion of the
      base of the bone was removed arthroscopically and to determine whether fragment
      size was associated with outcome. DESIGN: Retrospective study. ANIMALS: 26
      horses. PROCEDURE: Dorsopalmar and axial-abaxial lengths of the fracture fragment
      were measured on the dorsopalmar and mediolateral radiographic views,
      respectively, and percentage of the base of the sesamoid bone involved was
      estimated. Fractures were classified as grade 1 (< or = 25% of the base involved)
      or grade 2 (> 25% but < 100% of the base involved). Outcome was classified as
      successful if the horse started at least 2 races or unsuccessful if the horse
      started only 1 race or failed to return to racing. RESULTS: There were 24
      racehorses and 2 nonracehorses. Twelve (50%) of the racehorses returned to racing
      and started at least 2 races. Eight of 14 horses with grade-1 fractures and 4 of
      10 horses with grade-2 fractures had a successful outcome. Ten of 16 horses
      without associated articular disease had successful outcomes, compared with 2 of
      8 horses with associated articular disease. However, fragment size and presence
      of associated articular disease were not significantly associated with outcome.
      CONCLUSIONS AND CLINICAL RELEVANCE: Horses with basal fractures of the proximal
      sesamoid bone from which a fracture fragment involving a portion of the base of
      the bone is removed arthroscopically have a fair prognosis for return to racing.

PMID- 10909467
TI  - Pancreatic necrosis in New World camelids: 11 cases (1990-1998).
AB  - OBJECTIVE: To determine clinical, clinicopathologic, and postmortem abnormalities
      in New World camelids with pancreatic necrosis. DESIGN: Retrospective study.
      ANIMALS: 10 llamas and 1 alpaca. PROCEDURES: Medical records of animals in which
      a diagnosis of pancreatic necrosis had been made on the basis of histologic
      examination of necropsy specimens or on the basis of clinical signs and results
      of clinicopathologic testing were reviewed. RESULTS: The initial owner complaint
      varied, and various other conditions were diagnosed. Clinical and
      clinicopathologic abnormalities were vague. Amylase activity was higher in
      abdominal fluid than in serum in 5 of 7 animals, and lipase activity was higher
      in abdominal fluid than in serum in all 7. Four animals survived, and 7 died or
      were euthanatized. Only 1 of the animals that died had marked inflammation of the
      pancreatic parenchyma. All 7 had necrosis and saponification of fat in and
      surrounding the pancreas. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest
      that pancreatic necrosis may develop in New World camelids, but clinical signs
      are vague, and the condition may easily be confused with other diseases. The only
      laboratory test that appeared to be helpful in the antemortem diagnosis of
      pancreatic necrosis was comparison of amylase and lipase activities in abdominal
      fluid and serum.

PMID- 10909468
TI  - [Cytokines in children with immunodeficiencies].
AB  - The underlying immunological defect in humoral immunodeficiency with decreased
      production of immunoglobulin and normal level of circulating B cells (IgA
      deficiency, transient hypogammaglobulinemia of infancy, common variable
      immunodeficiency) remains unknown. There is evidence that B cells maturation and
      differentiation is regulated by cytokines and hence aberrant cytokine production
      may be involved in the pathogenesis of these diseases. Among interleukins, IL-1,
      IL-4, IL-6 and IL-10 may each play a role in regulation of B cell growth.
      Interferons (IFNs) have been described as having both positive and negative
      effects on B cell growth. The precise role of tumor necrosis factors (TNF alpha
      and beta) remains obscure. In the present study the in vitro cytokine production
      by peripheral blood mononuclear cells (PBMC) from children with different forms
      of immunodeficiency, in particular with IgA deficiency and transient
      hypogammaglobulinemia of infancy, was evaluated. In the first stage of the study
      the release of IL-1, IL-6, IFN and TNF by PBMC was analysed in following groups
      of patients: transient hypogammaglobulinemia (n = 30), IgA deficiency (n = 29),
      Bruton's disease (n = 7), decreased proliferative response to mitogenes (n = 10),
      CD4+ lymphocytopenia (n = 8), CD8+ lymphocytopenia (n = 10). The concurrent
      control group consisted 52 sex- and age-matched children, in whom no
      immunological immunological abnormalities were detected. The release of bioactive
      IL-1, IL-6, IFNs and TNF was measured in the culture supernatants from PBMC
      stimulated with mitogens for 48 hours. While the release of bioactive IL-1, IL-6,
      and IFNs was comparable in all studied groups, the secretion of TNF was
      significantly increased in children with transient hypogammaglobulinemia and IgA
      deficiency. The next issue was determination of the type of TNF (alpha or beta)
      involved. The production of other cytokines important for the regulation of B
      cell function (IL-4, IL-10) was also assessed. Production of TNF alpha, TNF beta
      and IL-10 was significantly elevated in transient hypogammaglobulinemia. The data
      from the ELISPOT assay suggested, that in these patients also the number of cells
      secreting TNF alpha after PHA stimulation was increased. These results indicate,
      that elevated TNF alpha production was probably due to both an enhanced release
      and an increased number of circulating secreting cells. As the methods employed
      in the quantification of cytokine levels in culture supernatants do not allow
      identification of the cytokine producing cell, the studies on intracellular
      expression of cytokines were undertaken. The fluorochrome-labelled monoclonal
      antibodies against the cell surface markers and a given cytokine were used
      simultaneously to identify the cellular source of cytokine production. The
      intracellular IL-4 expression in CD4+ lymphocytes from patients with transient
      hypogammaglobulinemia was comparable to that of control while the number of CD4+
      lymphocytes expressing TNF alpha, TNF beta and IFN gamma was elevated. The number
      of CD14+ cells (monocytes) producing of TNF alpha was comparable to the control.
      These results suggest that an excessive Th-1 type response may contribute to
      pathology of this disease. In patients with isolated IgA deficiency the
      significantly increased release of TNF alpha but not: IL-1, IL-4, IL-6, IL-10 and
      TNF beta was observed. The proportion of CD4+ lymphocytes that expressed TNF
      alpha was significantly increased while the number CD14+ cells staining for TNF
      alpha was unchanged. No changes in the expression of TNF type I and II receptors
      on PBMC were observed, which suggested that regulatory effects of TNF alpha and
      beta are associated rather with an increased production of these cytokines than
      an abnormal receptor expression. Some patients with transient
      hypogammaglobulinemia were followed-up and the serum level of IgG and production
      of TNF alpha, TNF beta, and IL-10 by their PBMCs was determined 6 to 12 months
      after first

PMID- 10909469
TI  - [Morphologic, morphometric and immunohistochemical studies on pancreatic
      intraductal hyperplasia and infiltrating carcinoma].
AB  - Pancreatic cancer belongs to the neoplasms which are characterised by increasing
      morbidity and mortality. Five-year survival rates of about 0.4% are the norm, and
      little has changed in the last 70 years. Important etiological factors are age,
      sex, diet, tobacco smoking, alcohol abuse, occupation and chemical exposure,
      hereditary chronic pancreatitis, and previous surgery (cholecystectomy and
      gastrectomy). The majority of exocrine tumours of the pancreas are malignant and
      80-90% of them comprise ductal adenocarcinomas. The development and growth of
      pancreatic carcinoma appears to be caused by a progressive accumulation of
      multiple genetic abnormalities. This includes oncogene (K-ras) activation, loss
      of tumour-suppressor p53 gene function and overexpression of growth factors and
      their ligands. The morphological background for the development of pancreatic
      carcinoma is ductal epithelial hyperplasia. Current molecular studies have
      resulted in the identification of cell clones exhibiting the same genetic
      alterations (K-ras and p53 mutations) as in infiltrating pancreatic carcinoma.
      Pancreatic intraepithelial neoplasia is only partially defined. The purpose of
      our study was to evaluate Ki-67 proliferative index and HER-2/neu gene expression
      in pancreatic intraepithelial proliferative lesions as a sign of increasing
      epithelial proliferation and dysplasia. Additionally we made an attempt to apply
      morphometry in demarcating between intraepithelial proliferations of "reactive"
      type and proliferations with tendency towards progression to cancer. Another aim
      of the study was to evaluate the expression of bcl-2 and p53 genes in various
      types of pancreatic intraepithelial proliferations and in pancreatic cancer and
      to answer the question whether they interact in the process of pancreatic
      intraepithelial neoplasia. We have also undertaken investigations aiming at
      determination of the CD44s gene and its v6 isoform expression in intraductal and
      invasive pancreatic carcinoma, attempting to correlate this expression with the
      p53 gene mutations. The results of our study indicate that intraductal pancreatic
      proliferations form a group of heterogeneous lesions possessing different
      proliferative activity of cells, karyometric features and HER-2/neu, bcl-2 and
      p53 genes expression. The precancerous lesion in the pancreas may be atypical
      papillary hyperplasia, which is similar to intraductal carcinoma with respect to
      the proliferative activity of cells and HER-2/neu, bcl-2 and p53 expression.
      Pancreatic carcinoma is characterised by high p53, CD44s and CD44v6 expression
      and low bcl-2 expression. CD44 and p53 genes expression is independent and
      between bcl-2 and p53 expression there is an inverse correlation. The p53 and
      CD44v6 expression is the higher the lower is the histological grade of the
      pancreatic carcinoma.

PMID- 10909470
TI  - [Barrett's metaplasia].
AB  - Reflux oesophagitis is a chronic disorder with one important complication-
      Barrett's esophagus, which is also called Barrett's metaplasia (BM). It is not
      known why only a part of the patients develops BM. In BM the normal squamous
      mucosa of the esophagus is replaced by columnar epithelium of intestinal type. BM
      is frequently diagnosed during endoscopical examination, particularly in man over
      60 years of age with symptoms of heartburn. This type of epithelium is a
      recognized risk factor of the esophageal adenocarcinoma. The incidence of this
      carcinoma is increasing in the last years. Based on the literature, we review the
      current pathogenesis, rules of diagnosis, surveillance and treatment of BM as
      well as the problem of connections between BM and esophageal adenocarcinoma.

PMID- 10909471
TI  - [Effects of antibiotic therapy on endoscopic examination of the upper
      gastrointestinal tract in children with Helicobacter pylori infections].
AB  - The aim of the study was defining the antibiotic influence for endoscopic picture
      of the upper segment of gastrointestinal tract in Helicobacter pylori infection.
      We remained retrospectively analysis of 790 endoscopies. In 62 of the analysed
      patients we found Helicobacter pylori infection. We divided these children into
      two groups. The first group, contained 15 children, who received antibiotics for
      the previous year, for any reasons. The second, comparative group was made up of
      47 children, who didn't receive antibiotics. We compared 18 characteristics of
      endoscopic picture in the oesophagus, stomach and duodenum mucosa. As a result of
      this study we conclude, that: 1) the most frequently the endoscopic changes were
      found in the stomach, as an erythema, an oedema and a nodularity of mucosa; 2)
      the inflammatory changes were in oesophagus and duodenum, as well; 3) we didn't
      observe the clear influence of antibiotics on the development of endoscopic
      changes in Helicobacter pylori infection; 4) in children, who didn't receive
      antibiotics, we observed polypus in the oesophagus, erosions in the stomach and
      ulcer in the duodenum. This may suggest the preventive role of antibiotics on
      intensity of gastrointestinal changes in Helicobacter pylori infected children.

PMID- 10909472
TI  - [Value of electrogastrographic parameters in evaluation of gastric myoelectrical
      activity].
AB  - Electrogastrography (EGG) is presently the only non-invasive method for the
      evaluation of gastric myoelectrical activity. In relation to the more and more
      described disturbances of the basic electrical rhythm in different pathological
      units EGG has been applied on a still larger scale. However, the data obtained
      from the EGG record do not reflect directly the gastric motility. This method
      allows only to make an indirect evaluation of the gastric motor disturbances. It
      still entails a great number of investigations so as to attain a better
      precisions of the evaluations of its clinical usefulness in gastroenterological
      diagnostics. This thesis presents the basic information on the methodology, the
      parameters under evaluation and the clinical application of the EGG method.

PMID- 10909473
TI  - [Autonomic nervous system and gastric myoelectric activities in type 1 and type 2
      diabetes].
AB  - The aim of the study was to compare autonomic function and gastric myoelectric
      activity in patients with type 1 and 2 of diabetes. We used the skin electrodes
      for recording gastric myoelectric activity (EGG) and the heart rate variability
      (HRV). Patients were divided into two groups. The first group: 19 patients with
      IDDM. The second-16 patients with NIDDM. We made two comparative control groups,
      matched with age and gender. We conclude, that decrease in gastric myoelectric
      activity was observed in both groups of patients, mostly in 1 group (IDDM) of
      patients. There was increase of heart rate and reduction of spectral analysis
      parameters in both types of diabetic. In patients with type 1 we noticed the
      increase of sympathetic activity (LF/HF ratio increased). In patients with type 2
      there was the non significant decrease in sympathetic activity (LF/HF ratio
      decreased). On the basis of our observations we confirmed the correlation among
      autonomic function tested by HRV and changes of stomach electric activity.
      Decrease in HRV and gastric myoelectric activity could be indicating damage of
      parasympathetic system in IDDM.

PMID- 10909474
TI  - [The influence of aging on autonomic nervous system activity and gastric
      myoelectric activity in humans].
AB  - The study was performed on 84 healthy volunteers (33 women, 52 men) of age 20-71
      years with no history of the circulatory or gastrointestinal system disease. The
      gastric myoelectrical activity (EGG) was recorded with the cutaneous electrodes-
      electrogastrography Synectics (Sweden). The activity of the cardiac autonomic
      nervous system was measured by HRV (heart rate variability) recorded with EGG and
      computer assisted programme Proster (Poland). Subject were divided into 5 groups
      according to the decade of age (20-70). Percentage of basal electrical rhythm
      (BER) dysrhythmias increased (1.9 +/- 0.5% vs 21.1 +/- 3.2% in fasting and 2.4 +/
      1.2% vs 24.6 +/- 5% postprandially but decrease of the EGG amplitude after the
      meal was observed (270 +/- 20% vs 90 +/- 7%) in youngest and oldest group
      respectively. With the ageing the cardiac sympathetic and parasympathetic
      activity (LF and HF) decreased in first and last group respectively. In the forth
      decade in man and women the sympathetic activity system prevalence expressed by
      the LF/HF rate increased (1.09 +/- 0.2 vs. 2.14 +/- 0.5) (p < 0.05). The results
      of our study suggest the deleterious influence of the ageing on the of autonomic
      system activity as shown by changes in HRV and dysrhythmia of the gastric slow
      waves in EGG.

PMID- 10909475
TI  - [Stomach electrostimulation--new possibility for treating gastroparesis].
AB  - This paper presents a large range of methods of human gastric pacing. Based on
      our own experience and literature authors discuss a variety of pacing models,
      current parameters and place of stimulation. We described a new method of
      intragastric stimulation as a method of treatment of postoperative,
      pharmacotherapy resistant gastroparesis. Five patients were included in to the
      study (3 male and 2 female). The current parameters were as follow: square
      profile, amplitude 2V (2mA), frequency 6 ips.p.m., duration 3 hours. Two
      electrodes located on nasogastric catheter (external diameter 1.5 mm) were placed
      in antral region of the stomach and connected to the computer preprogrammed
      stimulator. Electrostimulation was accompanied by the continuous cutaneous EGG
      monitoring (Synectics Sweden). Excellent results were obtained in 3 patients
      (60%) with disappearance of symptoms, rumbling, normalization in gastric
      myoelectric rhythm (2-4 cpm > 85%) and with increase in amplitude (average 250%).
      In one patient with the gastrectasia, symptoms returned next day and stimulation
      had to be repeated for several days. In another one results were not satisfying.
      Authors conclude that gastric pacing has made tremendous progress fast developing
      method in last decade and in most patient is efficient for treatment
      postoperative gastroparesis.

PMID- 10909476
TI  - [Gastric motility disturbances in pancreatic cancer patients].
AB  - Eighteen patients with confirmed pancreatic carcinoma without endoscopic evidence
      of mechanical gastroduodenal obstruction were included in the study. Aim was to
      determine changes in gastric myoelectric activity and liquid emptying (LGE)
      induced by pancreatic tumor growth. According TNM/UICC classification patients
      were divided in two groups A (T2) and B (T3) due to extend of expansion.
      Dyspeptic symptoms were observed in 4 patients of group A and 8 in group B. In
      group A dysrhythmic patterns of gastric myoelectric activity mostly bradygastria
      type were observed in 5 of patients and 8 in group B. LGE were delayed in 2 in
      group A and 5 in group B respectively. Disordered gastric myoelectric activity
      and emptying correlated with tumor stage and location. Delayed gastric emptying
      may be attributed to gastric dysrhythmia and abdominal pain that occur during the
      course of disease due to splamchnic plex infiltration.

PMID- 10909477
TI  - [The effect of pentagastrin on calcium ion concentration in gastric juice].
AB  - Calcium concentration in gastric juice is lower then other electrolytes. The
      mechanism of its transport remained unknown. The aim of the study was to evaluate
      influence of pentagastrin on calcium concentration in gastric juice in humans.
      Ten patients were examined (4 females and 6 males, mean age 46.8 range 33-67),
      four with duodenal ulcer, three with achalasia cardiae and three with Addison
      Biermer anemia. Pentagastrin--PG (Cambridge Laboratories, Newcastle, United
      Kingdom) was injected subcutaneously after overnight fast in dose of 6
      micrograms/kg of body weight. Nosogastric tube was located in body of the stomach
      near large curvature and connected to suction of--40 mmHg pressure. Gastric juice
      was collected during subsequent five 15 minutes periods (first fasted and four
      periods after stimulation with PG). Calcium concentration was measured in each
      sample by fluorescentic titration method with EGTA. Statistic analysis was
      performed with student "t" test. Mean fasted and stimulated calcium
      concentrations were 0.83; 0.44; 0.54; 0.37 and 0.95 mmol/l respectively. Ca2+
      concentration range in fasted state from 0.21 to 1.75 mmol/l and from 0.07 to
      0.27 mmol/l by maximal stimulation. Calcium concentration decreased immediately
      after stimulation (significance p = 0.0025). This strong effect persisted
      throughout the period of stimulation. Calcium output was 0.064; 0.029; 0.032;
      0.018 and 0.17 mmol/15 min respectively. Two phases of decrease of the calcium
      output were observed: first, fast decrease immediately after pentagastrin
      injection and second, slower, between 30 and 45 minute after stimulation (p <
      0.01 and 0.02 respectively). Calcium concentration in gastric juice decreases
      after stimulation with pentagastin (p = 0.0025). Calcium concentration was lower
      in Addison-Biermer anemia and higher in duodenal ulcer patients then in healthy
      control. We conclude that calcium ions are not actively secreted by gastric
      mucosa. Their presence in gastric juice is a result of leak from mucosal cells
      and remains opposite to their metabolic activity.

PMID- 10909478
TI  - [Sphincter of Oddi motility disturbances--etiologic factor or the consequence of
      choledocholithiasis].
AB  - Choledocholithiasis is often found in patients after cholecystectomy done
      previously for cholelithiasis. AIM: To evaluate the effects of cholecystectomy
      and common bile stones' presence on sphincter of Oddi (SO) motility. MATERIAL: 13
      patients with common bile duct stones (2 men and 11 women, age 54 to 85 yrs) were
      studied. They were divided in two groups: A--6 pts age 54 to 85 yrs (with biliary
      lithiasis) and group B of 7 pts age 55-71 after cholecystectomy.
      Cholecystectomized group was further divided into 2 groups according to
      administration (B1 group) or not (B2) a premedication. METHOD: Sphincter of Oddi
      manometry was done in all patients as the part of routine ERCP. A water-perfused,
      low-compliance, triple-lumen manometric system (Synectics Medical Sweden) was
      used to record the SO tonic and phasic activity. Common bile duct (CBD) pressure,
      basal SO pressure, SO phasic contractions frequency, duration and amplitude as
      well as direction of propagation peristaltic waves, motility index (MI) and AuC
      (area under curve) were measured. RESULTS: The CBD pressure, the basal SO
      pressure and the frequency of phasic SO waves tended to be lower in patients
      after cholecystectomy (p > 0.05). We observed profound changes in the motility
      pattern of SO phasic activity. There was significantly less anterograde and more
      retrograde waves in patients from group B than A (18.9% vs. 68.8%; p < 0.01 and
      52.4% vs. 10.4% respectively; p = 0.01). In the group B1 comparing with group B2
      we found significant decrease of frequency (1.8/min +/- 0.53 vs. 3.3/min +/-
      0.77; p < 0.05) and increase of the mean amplitude of phasic SO activity (223.2
      mmHg +/- 22.9 vs. 137.3 mmHg +/- 25.0; p < 0.01). The duration of pressure waves
      was prolonged (with long "plateau" or multipeaked) with rapid pressure increase,
      what resulted in high AuC index (1155.61 +/- 100.42 vs. 515.23 +/- 210.9; p <
      0.01). However no difference in MI was observed. CONCLUSION: Our results confirm
      hypothesis that cholecystectomy influences the pattern of phasic SO motility.
      Moreover increased percent of retrograde propagation of SO phasic contractions
      probably contributes to subsequent common duct stones development rather than
      being the consequences of their presence.

PMID- 10909479
TI  - Influence of continuous, isobaric rectal distention on smooth muscle tone and
      cardiovascular activation in healthy volunteers.
AB  - Interactions between visceral, intestinal stimulation and autonomic
      cardiovascular function have received increasing attention over the last years.
      The aim of the study was to investigate the effect of long-term continuous rectal
      distention on rectal tone and cardiovascular function at the threshold for first
      sensation of distention and moderate urge to defecate compared to a resting
      period without distention. Continuous isobaric rectal distention was performed in
      13 healthy volunteers with a ten minute pressure tracking procedure at each
      subject's predetermined individual threshold for either moderate urge or first
      sensation, separated by a ten minute resting period. Rectal volume, heart rate,
      systolic and diastolic blood pressure were determined continuously. RESULTS:
      Rectal tone decreased significantly over time at the threshold for moderate urge
      and first sensation. Cardiovascular measures remained stable over the distention
      procedures, except for a significant increase in systolic blood pressure at the
      threshold for moderate urge. DISCUSSION: The previously reported rectal
      accommodation response to rectal distention was confirmed. The increase in
      systolic blood pressure is most likely mediated through sympathetic efferent
      pathways.

PMID- 10909480
TI  - [Comparative analysis of bone mineral composition in human archeological material
      taken from different regions of Poland].
AB  - The actual paper presents the method and results of studies covering the mineral
      composition of the skulls of humans in the archaeological material stemming from
      different regions of Poland. The concentration of fluoride, zinc, iron,
      manganese, lead, calcium, magnesium and phosphorus was determined in 248 skulls.
      Distribution of individual burial sites providing the study material is presented
      in Fig. 1. The material was divided into four groups in relation to the place of
      deposition and in relation to the soil composition. Macro-, microelements
      determined by the method of atom absorption, phosphate by colourometric method,
      fluoride by potentiometric method. It has been disclosed that the bony material
      at the burial site is subjected to processes of fossilisation--replacing the
      organic matter by mineral one under definite soil conditions. The soil
      composition is the factor that influences the mineral composition of the bones in
      case of the following elements: zinc, manganese, lead, magnesium (Tab. 1). No
      influence was exerted by components contained in the soil on the determined
      concentrations of fluoride and iron in bones being explored from human skulls
      originating from archaeological excavation, undergo dynamic transformations in
      their mineral composition during their deposition in the soil. With the lapse of
      the time the content of fluoride (Tab. 2), magnesium (Tab. 7), calcium (Tab. 8),
      phosphate (Tab. 9) increases, while that of zinc (Tab. 3), iron (Tab. 4),
      manganese (Tab. 5) and lead (Tab. 6) decreases. The end concentration of elements
      in the archaeological bony material results from the following processes, namely:
      Cumulation, the example of which is the change in the concentration of fluoride,
      washing out the components of bone into the soil, to which the compounds of iron
      and manganese are subjected, compensations of concentrations of the bone soil
      border. That process took place in the case involving the changes in
      concentration of zinc, lead, magnesium, calcium and phosphate.

PMID- 10909481
TI  - [Activity of agglutinin inhibitor of the kujavian pea (Pisum sativum L.) in
      mothers' blood and umbilical cord blood considering the course of pregnancy and
      delivery].
AB  - The aim of the paper was to evaluate the activity of inhibitor of the
      phytoagglutinin Pisum sativum (IfPs) in sera of mothers' and umbilical blood of
      their newborns in confrontation with the course of pregnancy and delivery. The
      investigations involved 152 tests of sera collected from women delivering at
      Department of Obstetrics and Perinatology in the Institute of Gynecology and
      Obstetrics PMU in Szczecin in the years 1992-1993, as well as 156 samples of sera
      stemming from their newborn infants and were taken from the umbilical cord
      vessels. The method of investigations being used in the paper was the reaction of
      inhibiting the phytohemagglutination, wherein the inhibiting action of sera in
      bearing women and of sera in umbilical blood exerted on agglutinating one was
      assessed in relation to human erythrocytes of the group 0 with Pisum sativum
      lectin properties. The accepted titer of inhibitor of the agglutinin Pisum
      sativum (IfPs) was expressed as the highest dilution of serum, at which complete
      inhibition of phytohemagglutination was still preserved. The performed
      investigations have disclosed statistically significant differences between the
      activity of IfPs occurring in sera of the mothers and the inhibiting factor in
      umbilical blood sera of the newborns (Tab. 1). No effect of the duration of
      pregnancy and the course of pregnancy on the IfPs activity in sera of mothers was
      disclosed. The absence of inhibitor of Pisum sativum lectin in umbilical blood
      sera was essentially frequently recorded in premature termination of pregnancy
      between 31-37 weeks of its duration as well as in sera of newborns born by
      cesarean section and newborns with birth mass being equal or lower than 2500 g in
      comparison to sera of full term newborns born by forces of nature (Tab. 2, 3, 5).
      The birth status of newborns according to Apgar scale did not have any influence
      of IfPs activity in their sera, however, IfPs activity in sera of umbilical blood
      was statistically significantly more frequent in cases of deliveries lasting
      longer than 4 hours as compared to its activity in cases of deliveries being
      shorter than 4 hours (Tab. 4). On the basis of results of the performed
      investigations it has been revealed that at the period of intensive divisions of
      cells, their differentiation (intrauterine period of fetal development) the
      activity of the inhibitors of phytohemagglutination appearing in body fluids of
      human being is residual only or does not appear at all. The IfPs activity was
      intensifying with the progress of intrauterine maturation of the fetus. In the
      paper closer attention was focussed on the new point of view concerning the role
      of phytoagglutinins and endogenic lectins as well as their inhibitors in various
      pathological processes particularly neoplastic ones.

PMID- 10909482
TI  - [Influence of stimulation and inhibition of adrenergic receptors on ion transport
      in isolated rabbit trachea in electrophysiologic investigations].
AB  - Components of neural system in airways interact, and activation of one neural
      path can influence the releasing of mediators in other neural path.
      Electrophysiological investigations of mediators-influenced ion transport are one
      of many possibilities to study interactions between neural system in airway and
      airway's epithelium. Electrical transepithelial potential difference (PD) and
      transepithelial resistance (R) of isolated rabbit's tracheal wall were measured
      by using classical Ussing's method. Two types of stimulations applied on the
      tracheal mucosa were estimated; namely, the stimulation of adrenergic receptors
      by epinephrine (AD) and the mechanical stimulation (MS) by stream of fluid. The
      tissue reacted to both types of stimulations or was unresponsive in relation to
      both stimulations (Tab. 1). Changes of PD were reactions to AD or MS, whereas R
      remained without changes (Tab. 1 and 4). Ionic composition of the medium mimicked
      the composition of extracellular organism fluid. In such medium AD caused
      persistent depolarization of PD, whereas MS caused transient hyperpolarization of
      PD (Fig. 1). Regitin (RG) blocker of alpha-adrenergic receptors, beta-blocker
      propranolol (PR), and inhibition of prostaglandins synthesis by indomethacin
      diminished reaction of tracheal wall to AD (Tab. 2 and 3). Inhibition of chloride
      ions secretion by bumetanide diminished the reaction to AD, and lowered reaction
      to MS (Tab. 2). Inhibition of sodium ions absorption by amiloride had no
      influence on reaction after AD or after MS (Tab. 2). Indomethacin diminished
      reaction of the tissue to AD, while the reaction to MS remained without changes
      (Tab. 2). During the action of AD, RG, or PR reaction of tracheal wall to MS was
      upheld (Fig. 2, Tab. 4). Maintenance of reaction to MS despite previous influence
      on adrenergic receptors suggests that the epithelial cells, on the one hand, can
      be under adrenergic control and react in a manner being dependent on adrenergic
      system, and on the other hand they can independently respond to exogenous
      stimuli.

PMID- 10909483
TI  - [Edward Wilhelm Drescher--the founder of pediatric surgery in West Pomerania].
AB  - Professor Edward Wilhelm Drescher--an eminent Polish pediatric surgeon and
      pioneer of this specialization in West Pomerania--was born in 1912 in Bilgoraj.
      His young years he spent in his parents familial town Kalisz, where he attended a
      very famous college--State Humanistic Grammar-School. In 1937 he graduated from
      Faculty of Medicine at the Warsaw University. Next year he started his career as
      a surgeon in the Surgery at Orthopedic Ward of Pediatric Clinic in Warsaw, which
      was directed by prof. Jan Kossakowski--excellent pediatric surgeon and artist.
      During the September Campaign he took part in the battle of Bzura and in the
      defense of Polish capital as the physician in the 25th Regiment of Artillery. In
      1940 he joined Polish underground army--AK. In 1944, when the Warsaw Uprising
      broke out, he was the Commander of the insurgent hospital--Poznanska 11. It was a
      very well arranged and headed hospital, which admitted about eight hundred
      wounded soldiers and civilians. After the war for two years he lived in Sopot,
      where he organized and directed the Surgery Hospital and the Town Outpatients'
      Department. In 1947 he moved to Szczecin, where he arranged the first ward of
      pediatric surgery in West Pomerania (in Polish Red Cross hospital). Ten years
      later he was nominated the head of the Clinic of Pediatric Surgery in the
      Pomeranian Medical Academy in Szczecin. For many years Prof. Drescher was
      provincial and regional consultant. He helped to organize a few pediatric surgery
      wards in Pomerania (Koszalin, Gorzow Wlkp., Slupsk). He died in 1977 in Warsaw.
      Prof. Drescher published almost 80 scientific papers including two medical books.
      Traumatology of children and the newborn surgery became his principal area of
      interest. He was the author of Code of the Ethical and Moral Procedure of the
      Polish Medical Society. For almost twenty years he was co-author the Annales of
      Pomeranian Medical Academy. He was a co-founder, next was a president of the
      Polish Association of Pediatric Surgeons and next its honorary Member. Professor
      Drescher was well-known as a man of great humanist, an excellent teacher and
      surgeon with rich personality, getting easily into contact with every man,
      especially children.

PMID- 10909484
TI  - [Evaluation of factors affecting early and late outcome of 225 kidney
      transplantations].
AB  - The aim of this study was to evaluate some chosen factors affecting early and
      late outcome of 225 renal transplantations performed in the Department of General
      and Transplantation Surgery of the Pomeranian Medical Academy in Szczecin from
      1985 to 1995. Analysed groups were elected from this number in a way as to be
      comparable and their demographic data were discussed. Factors taken into
      consideration were: the impact of transplantation team experience, operator,
      graft perfusion method, preservation solution, multiple renal arteries, uretheral
      stent, multiorgan harvesting and donor sex. The early outcome was estimated as:
      immediate function, delayed function and nonfunction. The late outcome was: 3
      months, 1 year and 3 years graft and patient survival. Analysed groups were
      compared as far as an incidence of following surgical postoperative
      complications: urological, vascular, septic, graft rupture, bleeding, fluid
      collections and other surgical complications, is concerned. The data base was
      statistically elaborated using t-Student and Chi 2 test taking as statistically
      significant p less than 0.05. Results show that the impact of transplantation
      team experience was an important factor (Tab. 1, 2, 3). The comparison of three
      following groups of transplantations (75 cases each) elucidates that after
      learning period came a stabilisation period, in which the outcome is close to
      that achieved in other Polish transplantation centers. While investigating the
      factor of operator two groups of transplantations performed by seniors and one
      "learning group" were compared and no statistically significant difference was
      found. This is probably because each transplantation done by learning surgeon was
      assisted by one of above seniors. The perfusion method impact was investigated
      comparing two small groups (in situ and ex situ perfusion) and no benefit of any
      was proved. The difference between outcomes of groups in which UW or Eurocollins
      was used, was statistically significant as far as three years graft survival is
      concerned. In UW group it was 55.9%, whereas in Eurocollins group it was 29.4%.
      The probable explanation is that the possibility of longer cold ischemia time,
      given by UW solution, implicates more time to find better suited recipient for
      particular graft. The impact of multiple renal arteries on the outcome of
      transplantation was analysed by comparing group of 105 grafts with one artery and
      25 multiple arterias grafts. The immediate function occurred in 92% of group with
      multiple and 62.9% of group with one artery. The difference was statistically
      significant. The factor of indwelling uretheral stent was investigated comparing
      the group of 94 transplantations where it was used and the group of 35
      transplantations without it. There was no difference as far as urological
      complications are concerned. Multiorgan harvesting plays a very important role
      facing serious organ shortage in all developed countries. The comparison of 37
      multiorgan and 95 kidney harvestings showed no negative implications of the first
      one for the outcome of renal transplantations. Evaluation of donor sex factor did
      not show any essential differences while comparing group of 162 grafts taken from
      male and the group of 63 grafts taken from female donors. Following conclusions
      were established after discussion of above results: the most important factor was
      the impact of transplantation team experience; preservation by UW solution caused
      better late outcome of treatment; there was no negative influence of
      transplanting grafts with multiple arteries; the impact of operator, donor sex,
      perfusion method, multiorgan donation and use of uretheral stent was not proved.

PMID- 10909485
TI  - [NAT2* genotype in children with bronchial asthma and other atopic diseases].
AB  - There are still uncertainties as to the mechanism of many pathological
      conditions, among them atopic diseases. It has been disclosed that NAT2
      demonstrates genetic polymorphism and that the rate of acetylation catalyzed by
      this enzyme varies from subject to subject. The rate of acetylation appears to be
      an independent variable, specific for a given individual, genetically determined
      and associated with a dysfunction of the immune system. Therefore it is an
      important determinant of atopic diseases. So far, the NAT2* genotype has not been
      studied in patients with atopy and the results of some investigations on the rate
      of acetylation in allergy remain equivocal. The aim of this work was to evaluate
      the frequency of the NAT2* genotype in children with atopic diseases,
      particularly bronchial asthma, in their first-degree relatives and in healthy
      children. Furthermore, it was decided to check whether the NAT2* genotype may
      serve as a predispositing factor to atopy and whether the acetylation
      polymorphism is associated with the clinical course of these diseases. The study
      was performed in 266 children, including 85 patients with atopy and 181 healthy
      controls. Genomic DNA was isolated from peripheral blood and the NAT2* genotype
      was determined using PCR and restrictase digestion. The results shows that the
      NAT2* genotype, which is characteristic of slow acetylation, is an important risk
      factor in atopy, particularly bronchial asthma. A link between the clinical
      course of atopy and slow acetylation has been suggested.

PMID- 10909486
TI  - [Analysis of circumstances regarding deaths from tuberculosis in inhabitants of
      the Torun Province in the years 1990-1993 as an important factor in assessing the
      causes of tuberculosis treatment failure].
AB  - The aim of this study was to verify the diagnoses of tuberculosis in 98 cases of
      death from tuberculosis (TB) in Torun province in the years 1990-1993. The data
      of the official register of death were compared, with the hospital records and
      with the autopsy reports. Tuberculosis was accepted as the cause of death in all
      patients treated for sputum positive tuberculosis, and also in those in whom
      pathological proof of tuberculosis existed. In addition tuberculosis was accepted
      as the cause of death in 6 patients in whom no bacteriological examination was
      done, but who were tuberculosis contacts and who had the radiological picture of
      the lung compatible with tuberculosis. Those patients were admitted to hospital
      in terminal state and the permission for autopsy was refused. Tuberculosis was
      excluded as the cause of death in those who were treated for tuberculosis but
      were considered cured and also in those in whom a proof of other severe disease
      existed. Seventy two cases of tuberculosis death were officially registered in
      the above-mentioned time. In 23 of the 72 cases tuberculosis was excluded.
      Additionally 26 patients who died of tuberculosis were officially registered as
      death from other causes. After verification have found that 75 patients died of
      tuberculosis. In 26 of them the diagnosis was established only after death during
      the autopsy examination and/or positive culture for tubercle bacilli. In 27
      patients tuberculosis was diagnosed very late, 15 days before death in 12 and 30
      days in other 15 patients. In 19 patients the diagnosis was established 30 days
      or later before death. In majority of them, however, the treatment was
      interrupted or proceeding irregularly. It is concluded that: the real number of
      death from tuberculosis was similar to the registered although the errors in
      registered deaths from TB are in two directions; the main cause of death from TB
      in Torun province in the years 1990-1993 was the late diagnosis; the late
      diagnoses of tuberculosis was stabilized mainly in those who died at home and
      also in those who were admitted to hospital in critical state and died during the
      first two weeks of hospitalization.

PMID- 10909487
TI  - [Cortisol levels in blood of persons with acute myocardial ischemia and
      myocardial infarction].
AB  - An increase in blood level of Cortisol and overproduction of free radicals is
      present during first days following acute ischemia and myocardial infarction.
      This increase exceeds the activity of protective compounds and systems of
      myocardial cells undergoing ischemia. The aim of this work was to study the
      relationship between the Cortisol blood level and the intensity of free radical
      reactions in patients with acute myocardial ischemia and acute myocardial
      infarction with respect to metabolic (glucose, uric acid) and enzymatic agents of
      ischemia and necrosis. The study was performed in 75 patients (20 females and 55
      males) aged 38-75 years, including 13 patients with acute myocardial ischemia (6
      females and 7 males) aged 40-66 years (group I), 40 patients with acute
      myocardial infarction (8 females and 32 males) aged 38-72 years (group II) and 22
      healthy volunteers (6 females and 16 males) aged 39-75 years (control group). The
      concentration of Cortisol in blood and other biochemical determinants were
      measured on the second, fifth and seventh day following admission to the coronary
      care unit. The intensity of free radicals reactions was measured by using the
      concentration of Vitamin C, malondialdehyde (MDA), uric acid and white blood
      cells (WBC) count as markers. The results obtained have led to the following
      conclusions: 1. The increase in blood level of Cortisol in acute myocardial
      infarction is higher in comparison to the level of Cortisol in acute myocardial
      ischemia. 2. The intensity of free radical reactions during acute myocardial
      ischemia and acute myocardial infarction can be assessed by the decreased level
      of Vitamin C, increased level of malondialdehyde, uric acid concentration and
      leukocyte (WBC) count. 3. There is no correlation between the intensity of free
      radical reactions and elevation of blood cortisol during both acute myocardial
      ischemia and acute myocardial infarction. 4. Elevated levels of Cortisol in blood
      correlate with elevated levels of glucose and uric acid in blood during both
      acute myocardial ischemia and acute myocardial infarction. 5. Increase in
      enzymatic markers of ischemia and necrosis during acute myocardial ischemia and
      necrosis shows no correlation with the intensity of free radicals reactions.

PMID- 10909488
TI  - [Epidemiologic-clinical aspects of tick borne borreliosis in the Szczecin
      Province].
AB  - The aim of the study was to assess if Szczecin voivodeship is an area of endemic
      borreliosis, assess the risk due to B. burgdorferi infection in habitants and
      evaluate clinical manifestations of borreliosis. The study was conducted in 1993
      1995, material comprised 299 persons (211 men and 88 women) aged from 3 to 78
      years, divided into two groups. Group I consisted of foresters working in four
      forestry districts, occupationally exposed to tick bite. Group II was completed
      of Szczecin voivodeship habitants, sporadically exposed to tick bite. Control
      group consisted of 30 healthy persons without exposure to tick bite. Research
      programme of study comprised epidemiologic data, clinical examination, evaluation
      of serum anti-B.b antibodies in all persons and assessment of some infectious
      parameters (red cells sedimentation--RCS, leukocytosis and C-Reactive Protein-
      CRP) during borreliosis. High prevalence of borreliosis was noted in both groups.
      Risk of borreliosis was similar in four forestry districts (Tab. 1). The hazard
      of infection was not restricted to forest areas only but was present in some
      parts of Szczecin and its suburbs (parks and gardens). Infection by B.b. was
      observed in both males and females in all age groups. Risk of B.b infection
      increased accordingly to duration of exposure but in some examined persons after
      single tick bite the disease developed (Tab. 2). Some of infected persons do not
      demonstrate clinical symptoms of borreliosis (Tab. 3). In most cases the disease
      was diagnosed in early stage of infection (Tab. 4). During infection different
      organs and systems were involved (Tab. 5). In clinical study skin was the most
      often affected organ followed by nervous system and joints (Tab. 5, 7). Clinical
      manifestations comprised erythema migrans chronicum, radiculitis, arthritis,
      meningitis, encephalitis and uveitis (Tab. 6). Serological study revealed the
      presence of serum anti-B.b antibodies in 47.6% of examined persons with
      occupational risk involving tick bite, and 32.7% persons of sporadic risk with
      negative serology of borreliosis in control group (Tab. 8). The parameters of
      acute inflammatory phase (RCS, CRP, leukocytosis) are of limited value in
      diagnosis of borreliosis.

PMID- 10909489
TI  - [Evaluation of nervous system disorders during the course of gastric carcinoma on
      the basis of clinical electrophysiologic analysis].
AB  - The complex of neurological symptoms, which occur in the course of neoplasms of
      the internal organs and caused by the distant effect of the neoplasm on the
      nervous system, excluding other factors which could be responsible for changes in
      the nervous system, is called the paraneoplastic syndrome (PS). Pathogenesis of
      PS has not been clearly explained so far. Besides toxic, metabolic and infectious
      causes, the autoimmunologic one is taken into consideration. Paraneoplastic
      syndrome is mostly evoked by the oat cell carcinoma, subsequently by the breast,
      ovary and rarely by gastric carcinoma. The aim of the work was to determine: 1)
      the changes in the electroneurographic as well as visual and auditory evoked
      potentials examinations in the course of gastric carcinomas, 2) the influence of
      the treatment applied in gastric carcinomas on changes in visual and auditory
      evoked potentials and electroneurographic examinations. The examined group
      included 33 patients with diagnosed gastric carcinoma and having no clinical
      symptoms of lesion of the central and peripheral nervous systems. The results
      were compared to the control group, which consisted of healthy volunteers and
      patients after ventricular resection because of the chronic peptic ulcer disease.
      Clinical, neurographic as well as visual and auditory evoked potentials
      examinations were carried out three times. I.--just after the diagnosis of the
      neoplastic disease, II.--after end of treatment, III.--after 18 months (on
      average) since the end of the therapy. All patients had operative treatment. A
      part of them had supplementary chemotherapy--EEP cycle (Etoposide, Epirubicin,
      Cisplatin) or 5-fluorouracil. On the basis of the performed examinations of
      patients with gastric carcinoma, without clinical symptoms of lesions of the
      nervous system, primary axonal sensory-motoric neuropathic changes were observed
      in 36%. Changes in visual and auditory evoked potentials were found only in
      patients over 65 years old in over 50%. In patients after chemotherapy they were
      observed in visual and auditory evoked potentials and electroneurographic
      examinations, which could be caused by neurotoxic side-effect of the cytostatics
      applied.

PMID- 10909490
TI  - [Evaluation of the repair process in mechanically injured rat bone stimulated by
      sodium fluoride with non-toxic doses].
AB  - The influence of sodium fluoride on the course of repair process in the
      mechanically injured rat bone was studied. Thirty six male Wistar rats aged 5
      months, weighing 460-540 g were investigated. The animals lived under standard
      conditions and were fed ad libidum with the standard LSM food including 0.7 mg/kg
      of fluorine on the average. The animals randomly divided into 3 groups that
      comprised study and control groups, 6 rats each. The rats in the first group were
      given water with 20 mg (1.05 mmol) of sodium fluoride per kg of body weight for
      24 h over a period of 2 weeks--group Ia. In the second group--IIa--animals were
      given water with sodium fluoride at a dose of 1.5 mmol/kg b.w./24 h for a period
      of 4 weeks. In the third group--IIIa--the animals were given sodium fluoride in a
      dose of 1.5 mmol/kg b.w./24 h for a period of 6 weeks. The rats from the control
      groups I, II and III were given water without sodium fluoride for the period of
      2, 4 and 6 weeks, respectively. At the beginning of the experiment a hole was
      drilled in both femoral bones in rat under barbiturate anaesthesia. According to
      the protocol the rats underwent ether euthanasia after 2, 4 and 6 weeks after
      surgery and the following samples were collected: blood from the heart for
      biochemical studies and both femoral bones for biochemical and histological
      studies. The following parameters were evaluated in blood serum: fluorine,
      calcium, magnesium contents, serum concentrations of urea, creatinine, bilirubin
      and activity levels of enzymes: aspartate aminotransferase, alanine
      aminotransferase, cholinesterase, base phosphatase. Fluorine, calcium magnesium
      and zinc contents were estimated in bone samples. The concentration of fluorine
      ions in animal serum after 2, 4 and 6 weeks of experiment increased significantly
      as compared with the corresponding controls. The highest fluorine concentrations
      were observed in serum of rats supplemented with NaF for 6 weeks. The fluorine
      concentrations in the bone tissue and fresh and dried granulation tissues in all
      studied groups also revealed statistically significant increase as compared to
      the controls. The rats fed with sodium fluoride for the period of 6 weeks
      revealed statistically significant increase of serum magnesium concentration as
      compared to the remaining study groups. Bone magnesium concentrations in animals
      fed with NaF for the period of 2 and 6 weeks were higher as compared to the
      corresponding control groups, with the highest differences observed after 6 weeks
      of experiment. Animals fed with sodium fluoride for the period of 6 weeks
      revealed increased serum calcium concentrations as compared to the study groups
      after 2 and 4 weeks of experiment. Similar results were achieved in bone tissue
      samples (Fig. 1 and 2, Tab. 1-6). Basing on the achieved results in biochemical
      studies and histological pictures it should be assumed that laboratory animals
      fed with sodium fluoride in doses recognised as non-toxic reveal intensified
      healing process within mechanically injured bones. The use of sodium fluoride led
      to accelerated chondrogenesis process in the area of insufficiently perfused
      bone, osteogenesis including temporary callus formation and mineralization of the
      new bone, as well as remodelling into mature lamellar bone. The greatest
      differences in the repair dynamics for both groups occurred between the second
      and fourth week of experiment. These results could be the base of clinical
      studies on application of the sodium fluoride in the acceleration of fracture
      healing.

PMID- 10909491
TI  - [Bacteriologic and clinical analysis of nosocomial infections in patients from
      the intensive care unit].
AB  - The aim of this study is to evaluate what pathogens are mainly responsible for
      infection among all hospitalised at our ITU patients, to define the influence of
      antibiotic use on the aetiology of nosocomial infection. The research was
      conducted on a six-bedded surgical ITU in a 700-bed teaching hospital from
      January 1995 till June 1996. In August 1995 we changed infection control
      protocols (more stress on: handwashing with antiseptic soaps and routine
      microbiological culture for early prediction of infection) and antibiotic
      guidelines on our ITU (third generation cephalosporins, fluoroquinolones and
      Vancomycin were used only as the last option and never in prevention). 1276
      samples for microbiological culture were obtained in routine manner. From 60%
      positive cultures 1216 strains were isolated (Tab. 1) and resistance to
      antibiotics were defined (Tab. 3). Monthly antibiotic consumption was expressed
      in defined daily dose (DDD) for 1000 hospitalisation-days. DDD = (X/Y)/Z x x
      1000, were: X-cumulative antibiotic consumption during analysed period (g), Y
      standard daily dose (g/24 h), Z-number of hospitalisation-days during analysed
      period (Tab. 2). Values were expressed as the mean +/- standard error (SE).
      Relationships between variables were analysed using linear correlation. All data
      were categorised for the frequency table. Statistically significant differences
      were considered to exist when calculated p values were less than 0.05. There were
      no statistically significant differences in the number of treated patients,
      length of stay and mortality rate on our ITU in 18 months. 58% of isolated
      strains were Gram-negative bacteria especially Pseudomonas aeruginosa (22%) and
      Acinetobacter spp. (16%) and Proteus spp. (9%). The commonly isolated Gram
      positive bacteria were Enterococcus faecalis (14%), Staphylococcus aureus (12%)-
      of which 90% were MRSA. In 8% of cases we have isolated Candida spp. Monthly
      antibiotic consumption was displayed in table 2. Trend analysis confirmed
      reduction in Ofloxacin, fluoroquinolones and Colistin consumption over 18 months
      period (Fig. 2). We observed statistically significant decrease in amount of
      isolated Proteus spp. strains from 70 in I'95 to 31 in II'95 (p < 0.05) and 10 in
      I'96 (p < 0.005). This observation was confirmed in trend analysis (Fig. 1). We
      have observed in analysed period improvement in activities of third generation
      cephalosporins and fluoroquinolones (Tab. 3). We have analysed the influence of
      antibiotic use on the aetiology of nosocomial infection. Table 4 shows
      statistically significant correlation between Acinetobacter spp., MRSA, MRSE
      isolates and antibiotics consumption. Crosstabulated variables analyses confirm
      MRSE outbreaks in periods when excessive amount of Amikacin (p < 0.05 for chi 2
      test, D Somer rate 0.59, V Cramer rate 0.67), aminoglicosides (p < 0.05 for chi 2
      test, D Somer rate 0.57, V Cramer rate 0.59), imipenem (p < 0.05 for chi 2 test,
      D Somer rate 0.44, V Cramer rate 0.60) and total antibiotics consumption were
      high (p < 0.005 for chi 2 test, D Somer rate 0.67, V Cramer rate 0.81) (Fig. 3).
      This study illustrates the influence of antimicrobial therapy on the species and
      the resistance of strains isolated in nosocomial infection. Restrictive
      antibiotics policy does not affect ITU outcome. Better strategies for antibiotic
      administration in the ITU setting may improve their efficacy and control the
      spread of nosocomial infection caused by multi-resistant organisms. Therefore,
      restrictive antibiotic policy would be mandatory in each hospital and department.

PMID- 10909492
TI  - [Evaluation of the value of color doppler ultrasound investigations in diagnosis
      of the most frequently occurring diseases of the scrotal pouch].
AB  - The objective of the work was to estimate the value of ultrasound investigation
      with the use of colour Doppler imaging in diagnosing diseases of intrascrothy
      structures. Epidemiology of pathological testis epididymitis and seminal cord as
      well as histomorphology of tumours in testes were discussed. Technique of
      radiological imaging of this area and rules of colour Doppler ultrasonography
      were presented. Investigations were performed, with apparatus Acuson 128 XP-10
      using colour Doppler, in presentation B and B-colour. The accomplished evaluation
      covered the localization, size, echostructure and blood supply, vascularization
      of the studied changes, and in defined cases (mainly inflammations, and malignant
      neoplasms), coefficient of RI flow resistance was determined. Ultrasound
      examinations with the implementation of colour Doppler were carried out in 306
      patients, aged from 15 to 75 years, who were divided into two groups. Group I-
      control comprised 70 patients, group II--236 patients, in whom the clinical
      examination revealed various pathological changes within scrota. In patients of
      group I no changes in the intrascrotal structures were observed in the clinical
      examinations however, ultrasound study detected small varicoceles in 8 patients,
      and in 2 tiny cysts in epididymis. In group II by ultrasound the following were
      diagnosed: 50 inflammations, 15 testotorsion, 45 hydroceleus, 36 tumours, 20
      traumas and 70 cases of varicocele. On the basis of the performed investigations
      it has been disclosed that colour Doppler USG examination is very useful in
      diagnosis of diseases, namely the so-called "acute scrotum"--trauma, torsion,
      inflammation of testis and epididymitis. It is also useful in differentiating
      inflammatory, neoplastic changes of testes and epididymidis, relying on the
      complex estimation of their echostructures, blood supply vascularization as well
      as the character of vascular flow. Differentiating only on the basis of spectrum
      of the flow and the value of resistance indicator is not sufficient. Doppler
      technique is of essential significance in preoperative diagnosis, concerning the
      varicocele and monitoring of the postoperative period allowing for the estimation
      of the therapeutic effectiveness (Fig. 1, 2, 3, 4).

PMID- 10909493
TI  - [Possibilities and efficacy of treating perio-endodontic syndrome type III].
AB  - The aim of the investigation was to assess two methods of the treatment of III
      type perio-endo syndrome by Simon, Glick and Frank. In group I only periodontic
      treatment was performed including scaling, root planing and curettage. In group
      II periodontic treatment was supplemented by endodontic therapy. The results were
      registered by: Plaque Index, Sulcus Bleeding Index, Sulcus Fluid Rate, Bone Lost
      Index EMR, pocket depth and tooth mobility; before treatment, 7 days after
      treatment, 6 weeks and 6 months after treatment. In group II in selected cases
      (teeth with vital pulp and pocket depth more than 6 mm), microbiological
      examination of the dental pulp and dental plaque from the pocket was carried out.
      The results showed that the periodontal therapy was not effective. In first
      group, after 6 months the teeths mobility was extend, the pocket depth was
      reduced by 1 mm only, in gingiva there was registered still with chronic
      inflammation and the bone growth was not significant. In the second group the
      teeth mobility was less significant, the pocket depth was reduced more than 3.5
      mm, in 21% persons the gingiva was in good health condition and the bone growth
      was significant (7.5%). The anaerobic bacteria were incubated in 9 probes of
      dental pulp for 10 examinations.

PMID- 10909494
TI  - [Comparative analysis of tissue reaction to acrylic resin materials in studies on
      Wistar strain rats].
AB  - The study takes up the issue of assessing rat tissue reaction to operatively
      inserted implants of different acrylic resin materials used in prosthetic
      dentistry. The materials subjected to analysis were polyacrylics: Vertex Soft,
      Vertex R.S., Vertex S.C., Superacryl and silicone material Molloplast B. The
      prolongation of life and the dynamic development of prosthetic treatment have
      caused removable dentures to be used longer and among more people. Polymerised
      acrylic resin material of these dentures is a potential pathogenic factor to the
      oral cavity mucosa which is in contact with it. As many as 20 to 70% of patients
      using removable acrylic dentures suffer from prosthetic stomatopathy. It is
      considered that the mucosa irritation may be caused by denture trauma, a mycotic
      infection or toxic action of some components of acrylic materials. Therefore the
      use of new generation acrylic materials in producing prosthetic dentures needs a
      precise assessment of undesirable local and systemic effects. A comparative
      analysis of the effect of correctly polymerised acrylic material on rat mucosa,
      parotid glands and lymphatic nodes was carried out. Systemic toxicity of these
      materials was assessed. Acrylic plates were prepared from the most often used
      acrylic resin materials in the Department of Prosthetic Dentistry PAM and a
      silicone material (these materials were polymerised precisely according to the
      producers instruction). Before implantation the plates underwent a thermodynamic
      analysis in order to ensure that the polymerisation process was carried out
      correctly and to determine thermal resistance of particular materials. Next
      sterile acrylic plates were implanted in rats under general anaesthesia. The
      animals were divided into 6 groups, 10 rats each. In four groups acrylic plates
      were implanted, in one group silicone material plates were implanted and it
      represented the comparative group, in one control group an incision of the buccal
      mucosa was made. The rats were observed during a period of 6 weeks, they were
      weighed every two weeks and no loss in body mass was noted (Tab. 1). After 6
      weeks the rats were anaesthetised with ether and dissectioned. Biopsy specimens
      were taken from the buccal mucosa, porotid gland and lymphatic cervical nodes
      around the plates in order to make histological specimens. Blood samples were
      also taken to carry out blood cell counts and liver tests to determine eventual
      systemic toxicity of the studied acrylics. Histological specimens were stained
      with hematoxylin and eosin. In borne cases in order to precisely assess the
      intercellular substance other staining methods were used such as van Gieson, PAS
      and silvering of precollagen fibres on reticulum. Prepared specimens were
      assessed in a light microscope in magnification of 80 to 400. Basing on specimens
      of the control group an analysis of tissue reaction to the particular tested
      acrylic resin material was carried out. It was ascertained that the most
      irritative properties to the rat buccal mucosa were caused by self-cure acrylic
      material--Vertex S.C. This polymer caused in all rats in the tested group a
      reactive hypertrophy of cervical lymphatic nodes (Tab. 2 and Fig. 3). The least
      damaging effect on the surrounding tissues was caused by heat-cured acrylic resin
      material Superacryl (Fig. 4). The tested materials had no damaging effect on the
      rat parotid gland and did not have a toxic action on the internal organs.

PMID- 10909495
TI  - [The effect of selected prophylactic-educational programs on oral hygiene,
      periodontium and caries in school children during a 4-year observation].
AB  - The aim of the work was the continuation of the evaluation of the efficacy of
      three prophylactic-educational programs in the field of oral cavity hygiene,
      status of periodontium and dental caries, and their influence on the forming of
      pro-health awareness and correct hygiene habits among school children. The work
      under discussion is the second stage of observations of the above-mentioned
      programs as well as the complete evaluation of 4-years examinations. The clinical
      and questionnaire studies were carried out in two elementary schools in Szczecin.
      Two hundred and twenty-three pupils were randomly allocated to three test groups:
      I (45 children), II (71 children), III (60 children) and control group K (47
      children). In both schools mentioned above the examinations started when children
      were 7-8 years old and all of them were receiving planned stomatological
      treatment and contact fluoridation. All programs of the second stage of studies
      were the same as those of the first stage [49], only with the modified frequency
      of meetings with children. Program I, carried out in group I, was based on
      individual, motivating instructions of oral cavity hygiene (total 10 meetings
      during second stage of research). Programs II and III (group II and III
      accordingly) were expanded by educational activity among children and their
      parents. Additionally program III was enriched by professional mechanical tooth
      cleaning, the use of fissure sealants, intensive dental care and proximal surface
      cleaning with dental floss (Tab. 1). The above-mentioned programs were carried
      out in co-operation with school dentists, teachers, fifth year dentistry students
      and students from Medical College--Oral Hygienist Faculty. After 4-years-long
      studies the evaluation of the three above-mentioned programs in oral cavity
      hygiene was achieved by using OHI-S and PI(QH). The status of periodontium was
      evaluated by GI and the intensity of dental caries by DMFT and DMFS. The increase
      of caries during the second stage of examinations was additionally evaluated and
      analysed thoroughly. The questionnaire studies made it possible to estimate the
      changes in the pro-health awareness among examined children. Reduction of OHI-S
      after 4 years was about 23% to 26% (Fig. 1). The status of gums shows the state
      of oral cavity hygiene in a better way. In control group the state remained
      unchanged, but in groups I, II and III it improved considerably (reduction of GI
      about 46% to 79%--Fig. 2). The reduction of caries in examined groups obtained
      after 4 years of studies was about 25% to 77% (Fig. 3) however during the second
      stage of research if figured out from 17% up to 72% (Fig. 4). Extreme increase of
      DS observed in the second stage of studies was 2.0 in control group K, a little
      less--1.51 in group I and 0.38 in group III (Fig. 5). The DS in group III reached
      the value -0.27 which proved that program III was the most efficient. The results
      of questionnaire studies showed a distinct improvement of health awareness among
      examined children. However the value of GI indicated some discrepancy between
      children's health knowledge and pro-health behaviour. Also it was noticed that
      the level of parents' education and their socioeconomic status had influence on
      building up good hygiene habits and on the state of caries among the examined
      children. The studies proved that the implementation of the above-mentioned
      prophylactic-educational programs or similar ones in elementary school conditions
      is possible with the use of hygienist under the dentist's supervision.

PMID- 10909496
TI  - [Comparative studies of two different systems for bonding composites with tissue
      of the tooth].
AB  - The objective of studies was the clinical evaluation concerning the influence of
      the bonding systems Syntac and Gluma exerted on the quality of compositive
      fillings in various types of defects in humans, in comparison to fillings, in
      which Compa Bond resin was used. The question was studied to answer whether there
      were any significant differences in respect of the assessed parameters between
      fillings by Syntac system and the fillings by Gluma system with preservation and
      marginal adaptation being taken into consideration. The studies were performed on
      98 patients of both sexes, therein 56 women and 42 men. The assessment included
      248 classified fillings, namely: 82 of Tetric material, 78 of Pekalux material
      and 88 of C-Fill MH and C-Molar materials. The fillings were estimated directly
      after placement, as well as after 6, 12, and 24 months, under artificial light by
      making use of dental mirror, a probe and an optic device (magnifying glass of
      fivefold magnification), on the basis of own card of investigations for
      compositive fillings. The dental pulp reaction to thermic simuli and faradic
      current was also taken into account. Fillings classified by grades 0 degree and 1
      degree were defined as clinically acceptable, while 2 degrees and 3 degrees as
      clinically unacceptable. The statistical analysis was carried out by means of Chi
      2 test. The number of Tetric and Pekalux materials fillings lost after 24 months
      of studies was substantially lower than the number of lost fillings made of C
      Fill MH and C-Molar materials. The loss only concerned defects of non-carious
      origin, namely wedge shaped defects and pathological attrition of teeth (Tab. 1
      and Tab. 2). The fillings by Syntac system are characterized by better marginal
      adaptation as compared with fillings, wherein the Gluma system was applied,
      however, no statistically significant differences between these groups were
      disclosed (Tab. 3). Significant differences were found to appear between the
      groups, of fillings, in which use was made of bonding systems Syntac and Gluma on
      the one hand, and the fillings set up by Compa Bond resin on the other. Assessing
      the colour, smoothness of surface and the anatomical shape of the fillings after
      24 months no essential differences between the studied material groups were
      revealed. Secondary caries and post-procedural sensitivity involved only the
      cases, in which Compa Bond resin and C-Fill MH material were employed. After 24
      months of studies the percentage of clinically acceptable fillings claimed to be
      as follows: Tetric 93.51%, Pekalux 91.55%, C-Fill MH and C-Molar 75.36%. Thus, it
      was disclosed that there were significantly more clinically acceptable fillings
      made of Tetric and Pekalux materials than of C-Fill MH and C-Molar materials. The
      Syntac and Gluma systems exerted significant influence on better preservation and
      marginal adaptation of fillings mainly in defects of non carious origin, in
      comparison to the fillings in which the conventional Compa Bond resin was being
      used. In cases, wherein Syntac and Gluma systems were applied, no post-procedural
      hypersensitivity was recorded. This ailment was evidenced in 4.5% of cases after
      implementing Compa Bond resin.

PMID- 10909497
TI  - [Enhancing cultural sensitivity of psychiatrists emigrating from Russia to
      Israel].
AB  - The importance of understanding the local culture and enhancing cultural
      sensitivity became evident during supervision of immigrant psychiatrists from the
      former Soviet Union. The aim of the present study was to describe enhancement of
      this cultural sensitivity in the supervision of 2 immigrant psychiatrists. In the
      first, understanding the patient's cultural world helped the immigrant
      psychiatrist form the therapeutic alliance. In the second, the immigrant
      psychiatrist's understanding of the patient's cultural background led him to
      change both diagnosis and treatment. In both cases, development of cultural
      sensitivity through supervision enabled successful treatment. Enhancement of
      cultural sensitivity may accelerate absorption of the immigrant psychiatrists
      themselves. Discussing cultural issues during work may accelerate the absorption
      of all immigrant physicians.

PMID- 10909498
TI  - [Does testicular volume reflect spermatogenic pattern in men with azoospermia?].
AB  - The aim of this study was to determine whether testicular volume can serve to
      predict patterns of spermatogenesis in azoospermia. In 27 tests of azoospermic
      infertile men, cytological specimens from several sites from each testis were
      obtained by fine needle aspiration. Testes were classified according to the most
      mature spermatogenic cell type. Classifications were testes with spermatozoa,
      with arrested spermatogenic development, and with only Sertoli cells. Prior to
      fine needle aspiration the 3 dimensions of each testis were determined
      ultrasonically and its volume calculated. Mean testicular volume (+/- SD) was
      7.71 (+/- 5.95) ml for testes with spermatozoa and 7.55 (+/- 2.35) and 7.31 (+/-
      4.42) ml for testes with spermatogenic maturation arrest and with only Sertoli
      cells, respectively (differences not significant). It is concluded that
      testicular volume can not be used as a predictive parameter, neither for the
      presence of spermatozoa nor for the cytological pattern of the testes of
      azoospermic infertile men.

PMID- 10909499
TI  - [Diagnosis of cerebral embolism by transesophageal echocardiography].
AB  - Cerebrovascular events have high mortality and morbidity, especially in the
      elderly. Ischemia is the main cause and 30% of the ischemic events are embolic
      and of cardiac origin. The clinical picture is not always typical of the type of
      stroke, but diagnosis of the mechanism of the event determines treatment.
      Transesophageal echocardiography (TEE) is a sensitive procedure more appropriate
      for diagnosing emboli of cardiac origin than transthoracic echocardiography
      (TTE). We therefore compared TEE and TTE in the determination of the source of
      emboli in 65 patients with ischemic stroke but without significant
      atherosclerotic changes in their carotid arteries, and compared these findings
      with those in 50 patients without stroke. 68% of the patients had potential
      sources of emboli according to TEE, compared to only 15% according to TTE. In the
      control group only 24% had potential sources of emboli by TEE. The findings were:
      clots in the left atrium, severe aortic atheroma, patent foramen ovale with
      paradoxical shunt, spontaneous echocardiography contrast, vegetations and mitral
      valve prolapse. The study showed that TEE is better than TTE in detecting the
      etiology of embolic stroke in those with normal carotid arteries, thus
      determining appropriate management.

PMID- 10909500
TI  - [Screening for transitional cell carcinoma of the bladder with trophoblastic
      differentiation in Upper Galilee].
AB  - Urinary bladder carcinoma with trophoblastic differentiation (TD) is a variant of
      urothelial (transitional cell) carcinoma (TCC) which secretes placental proteins,
      predominantly beta-human chorionic gonadotropin (HCG). An aggressive clinical
      course and a poor prognosis are characteristic of this tumor. We evaluated the
      frequency and clinical and pathological appearance of TCC-TD in the Upper Galilee
      and Golan Heights between 1988 and 1995 inclusive. Beta HCG, human placental
      lactogen (HPL), pregnancy specific beta-1 glycoprotein (SP-1) and placental
      alkaline phosphatase were determined immunohistochemically in paraffin-embedded
      TCC of urinary bladder. Tumor grade, stage and patient survival were also
      determined. There was beta-HCG immunostaining in 13 of 62 cases (20.9%). TD was
      correlated with higher grades of TCC and with advanced stages of disease. No
      cases of TCC-TD were found in grade 1, stage 0. Co-expression of beta-HCG and HPL
      was displayed in 2 cases, beta-HCG and SP-1 in 9, and beta-HCG, HPL and SP-1 in
      2. Disease-free survival and overall survival were shorter in TCC-TD.

PMID- 10909501
TI  - [Recurrent syncope as a presenting symptom of systemic mastocytosis].
AB  - A 48-year-old man presented with recurrent syncope which was preceded by facial
      edema and difficulty in breathing. Physical examination, laboratory tests,
      abdominal CT and bone scan were all within normal limits. Bone marrow biopsy was
      consistent with mastocytosis. Systemic mastocytosis consists of a spectrum of
      disorders characterized by aberrant proliferation of tissue mast cells, and are
      mainly related to mast cell mediator release.

PMID- 10909502
TI  - [Acute liver damage after using ecstasy].
AB  - Ecstasy is a stimulant used mainly by youngsters to get 'high.' There are few
      reports of acute injury of the liver due to ecstasy. We describe a 37-year-old
      woman who presented with the clinical picture of recurrent hepatitis following
      ingestion of the drug. After several months she developed liver cirrhosis shown
      by biopsy and CT scanning. This case emphasizes the potential danger of ecstasy.
      Every patient with hepatitis of unknown origin must be questioned about ingestion
      of the drug.

PMID- 10909503
TI  - [Pelvic lytic lesion, and the need to suspect osteoporosis-related fractures].
AB  - Insufficiency fractures of the pelvis may be overlooked as a cause of hip or
      groin pain. These fractures occur in the elderly, usually those with pronounced
      osteopenia of the pelvis. Predisposing factors include corticosteroids, local
      irradiation and postmenopausal osteoporosis. These fractures are difficult to
      detect clinically and plain radiographs and other studies may be misleading,
      delaying diagnosis and treatment. A 65-year-old woman had left groin and hip pain
      for 2 months with no history of trauma. Plain radiographs showed lytic lesions in
      the left pubic rami. Bone scan revealed increased uptake in that region,
      suggesting metastatic bone disease. Computed tomography and magnetic resonance
      imaging demonstrated fractures in the left superior and inferior pubic rami, with
      callus formation with no involvement of soft tissues. Quantitative computed
      tomography indicated low calcium concentration, below fracture threshold. The
      diagnosis of insufficiency fractures of the pelvis was confirmed by the favorable
      clinical and radiographic outcome. It is therefore important to be familiar with
      the appearance and location of these fractures.

PMID- 10909504
TI  - [Intra-osseous ganglion of scaphoid and lunate bones].
AB  - We present a patient with intra-osseous ganglion of the left scaphoid and lunate
      bones. These were excised and a bone graft inserted. 1 year after operation the
      patient was free of pain, without limitation of wrist motion. Intra-osseous
      ganglion of the carpal bone is not common and lunate and scaphoid intra-osseous
      ganglion has rarely been reported. Awareness of this condition may lead to
      earlier diagnosis and treatment, with satisfactory outcome.

PMID- 10909505
TI  - [Antiphospholipid syndrome and vasculitis--just a coincidence?].

PMID- 10909506
TI  - [Loss, bereavement and depression--recent findings].

PMID- 10909507
TI  - [Intracytoplasmic sperm injection--hopes and risks].

PMID- 10909508
TI  - [Liquid ventilation in newborns and premature infants].

PMID- 10909509
TI  - [Liquid ventilation with perfluorocarbons].

PMID- 10909510
TI  - [Prenatal screening for Down's syndrome--moving from the second to the first
      trimester of pregnancy].

PMID- 10909511
TI  - [Helicobacter pylori--a model for colonization and survival in a hostile
      environment].

PMID- 10909513
TI  - [Bone sarcomas (Part I)].

PMID- 10909512
TI  - [Somatostatin--a multisystem regulatory hormone with immunomodulatory effects].

PMID- 10909515
TI  - [A psychiatrist looks at family medicine].

PMID- 10909514
TI  - [Recurrent aphthous stomatitis].

PMID- 10909516
TI  - [Psychiatry, family medicine and humanism--Yehuda Fried's legacy].

PMID- 10909517
TI  - [Treatment protocol for secondary prevention in patients with coronary heart
      disease].

PMID- 10909518
TI  - [Stress fractures].

PMID- 10909519
TI  - [Florence Nightingale--in historical perspective].

PMID- 10909520
TI  - [Viagra--the first oral treatment for impotence that is not lacking in fatal
      effects].
AB  - Impotence, a common problem especially among older men, can now be treated with
      Viagra, This oral pill, unlike previous approved treatments mostly involving
      local injections, does not directly cause penile erection, but increases response
      to sexual stimulation. It acts by enhancing the relaxant effects of nitric acid
      on smooth muscle, and thus increases blood flow to certain areas of the penis,
      leading to erection. It has been evaluated in many randomized trials and in all
      was more successful in inducing erection than placebos. The most common side
      effects include headache, flushing and indigestion, but there have also been
      reports of fatalities. We describe a 75-year-old man who had an acute myocardial
      infraction in the past and who had maturity-onset diabetes and hypertension. In
      the week prior to admission he had a cardiac scan following a few weeks of
      exacerbation of anginal pain for which he had been taking nitrites. He took a
      Viagra pill without prescription or medical advice and 2 hours later, during
      intercourse with his wife, developed audible respiratory distress and lost
      consciousness. His wife started cardiac massage but not mouth-to-mouth breathing.
      The emergency team found ventricular fibrillation and gave 5 electrical shocks
      and amines and atropine. He remained unconscious, but his pulse returned and he
      was hospitalized. He then had several generalized convulsions treated with i.v.
      valium. 20 minutes after admission there was asystole and all attempts at
      resuscitation failed. Cardiovascular status must be considered prior to
      prescribing Viagra, and the associated risk evaluated.

PMID- 10909522
TI  - [The electroencephalogram in psychiatric patients].
AB  - 270 consecutive electroencephalograms (EEGs) performed in a psychiatric hospital
      were reviewed. 194 (75%) were within normal limits but 66 (25%) showed diffuse
      generalized slowing. The contribution of the abnormal EEGs to diagnosis and
      treatment was evaluated by retrospective file review. In none of the cases with
      abnormal EEGs was there a relationship to diagnosis or treatment.

PMID- 10909521
TI  - [Brucellosis in pregnancy].
AB  - Brucellosis is rare in pregnancy. Recently, an increase in the incidence of this
      disease has been observed in our area. We present 7 cases of brucellosis in
      pregnancy and review the literature on the effects of brucellosis on the outcome
      of pregnancy. Brucellosis is rare in the Middle East and Africa and the most
      common source of infection is unpasteurized milk products. Brucella is a
      coccobacillus, gram-negative bacterium, whose hosts are mostly animals. There is
      controversy about the relationship between brucellosis and the outcome of
      pregnancy. There is some evidence that there is a higher rate of complications
      such as abortion, premature rupture of membranes and preterm delivery in infected
      animals. Reasons for this difference in the impact of brucella in animals and man
      include the absence of the carbohydrate erythritol in the human placenta, which
      appears to be a preferential medium and growth factor for brucella in the
      placentas of animals. There is uncertainty regarding effects of brucella in early
      pregnancy and no evidence of its transplacental passage in later pregnancy,
      causing adverse obstetrical outcome, although recently there has been a single
      report of Brucella abortus (biotype 2). We present 7 cases of brucellosis in
      pregnant women found between 1977-1988. Its incidence among the women who
      delivered here is 0.007% (7/92, 768 deliveries). Our first case was complicated
      by preterm premature rupture of membranes and preterm delivery in the 20th week
      of gestation. In 2 other cases there was preterm delivery with 1 developing
      clinical chorioamnionitis. The 4 remaining women delivered at term, although 1
      had preterm premature rupture of membranes and intra-uterine growth retardation,
      and 2 had postpartum endometritis.

PMID- 10909523
TI  - [Preservation of the great posterior auricular nerve during superficial
      parotidectomy].
AB  - Sensory loss in the operative area after superficial parotidectomy is one of the
      complications which disturbs the patient. The greater auricular nerve, which
      stems from the cervical plexus, supplies sensation to the area. Sacrifice of the
      nerve during superficial parotidectomy causes sensory loss in the area. We
      investigated the degree of sensory loss in the operative area after superficial
      parotidectomy in 10 patients in whom the posterior branch of the greater
      auricular nerve was preserved and compared the results with those in whom it was
      not, a year after operation. There was more sensory loss when the greater
      auricular nerve was sacrificed. We therefore suggest preserving the posterior
      branch of the greater auricular nerve during superficial parotidectomy if at all
      possible.

PMID- 10909524
TI  - [Incarcerated diaphragmatic hernia presenting as colonic obstruction].
AB  - Diaphragmatic hernias in adults that are not categorized as hiatal hernias are
      rare. Hernias of the diaphragm itself appear in the perinatal age group and are
      defined as congenital hernias, presenting with severe respiratory distress and
      requiring immediate repair. There are a few asymptomatic post-partum cases in
      young children or adults. We present 3 cases of diaphragmatic hernia in men, aged
      19, 20 and 74, respectively. 2 were admitted because of colonic incarceration
      with strangulation in the hernial sac. In the other case there was an incidental
      finding of incarcerated colon in a diaphragmatic hernia discovered in a patient
      who initially presented with unrelated thoraco-abdominal trauma. Contrary to the
      dominant clinical presentation as infant-respiratory distress, the predominant
      findings in adults are gastrointestinal complications. We believe successful
      treatment is more likely when there is a high level of awareness of the
      possibility of this kind of hernia in the adult, which can be a recurrence after
      perinatal hernia repair. It is essential to recognize that this is a combined
      thoraco-abdominal problem since it is often necessary to perform simultaneous
      laparotomy, thoracotomy and stoma formation.

PMID- 10909525
TI  - [Discitis in brucellosis is not responsive to anti-brucella treatment].
AB  - A 14-year-old girl with fever and low back pain was diagnosed as having
      brucellosis and diskitis. Treatment with doxycycline and gentamicin had no effect
      nor was there any improvement when the treatment was changed to doxycycline and
      rifampicin. With cessation of this treatment and administration of cloxacillin
      fever was reduced and the back pain disappeared. After 12 days of i.v.
      cloxacillin, she was released from hospital with instructions to continue
      cloxacillin orally for another 4 weeks. We conclude that when a patient is
      suffering from brucellosis and diskitis and does not respond to the usual anti
      brucellosis treatment, an anti-staphylococcal preparation should be added.

PMID- 10909526
TI  - [Leiomyosarcoma of the stomach].
AB  - Gastric leiomyosarcoma (GLMS) is a malignant, smooth muscle neoplasm accounting
      for not more than 0.45%-3.5% of primary gastric malignancies and 17%-20% of all
      smooth muscle tumors of the stomach. A well-characterized variant has been
      variously referred to as leiomyoblastoma and epithelioid leiomyosarcoma. Because
      of the rarity of GLMS, few authors have tried to correlate clinical presentation,
      pathological findings, and treatment. There is no uniform therapeutic approach
      for leiomyosarcoma of the stomach and reported survival rates vary widely. We
      present a 56-year-old man whom we treated for this condition.

PMID- 10909527
TI  - [Viagra--utility and risk].

PMID- 10909528
TI  - [Clinical pharmacology--a new medical specialty in Israel].

PMID- 10909529
TI  - [Viagra].

PMID- 10909530
TI  - [The role of brachytherapy in the modern treatment of cancer].

PMID- 10909531
TI  - [Surgical treatment of primary cutaneous malignant melanoma--historical aspects
      and current trends].

PMID- 10909532
TI  - [Glycoprotein IIB/IIIA receptor blockers as treatment of acute coronary syndromes
      and interventional cardiology].

PMID- 10909533
TI  - [Parameters in early prediction of bronchopulmonary dysplasia in preterm
      infants].

PMID- 10909534
TI  - [Current treatment of bleeding esophageal varices].

PMID- 10909535
TI  - [Laparoscopic surgery in urology].

PMID- 10909536
TI  - [How did King Asa die].

PMID- 10909537
TI  - [Are there good ways to deliver bad news about a child].

PMID- 10909538
TI  - [Infectious disease in the Middle East: geopolitics versus epidemiology].

PMID- 10909539
TI  - [The rheumatoid foot].

PMID- 10909540
TI  - [Professional assessment of senior physicians who immigrated to Israel up to
      1996].
AB  - Israel has absorbed many immigrant physicians and has utilized their skills
      without compromising local professional standards. In accordance with this policy
      a special law for the assessment of the licensing of senior immigrant physicians,
      mainly from the former Soviet Union, who had practiced medicine for at least 14
      years was implemented in 1994. Considering their considerable medical experience
      on the one hand and their lack of experience in speaking Hebrew or undergoing
      testing techniques, they were exempted from the written national licensing
      examination. Instead they were obliged to undergo a 6-month clinical observation
      period in a local hospital or clinic. At the end of this period a letter of
      confirmation was issued which was followed by an oral assessment of their
      clinical ability. In the assessment session, each candidate was presented with
      written presentations of 4 typical clinical cases which practitioners encounter
      on a daily basis, in family medicine, emergency medicine, surgery, and pediatrics
      or gerontology. Of 114 cases prepared, 4 were selected for each candidate by the
      committee of 13 trained, experienced Israeli physicians. 3 members of the
      committee assessed each candidate using specified criteria. The assessment, which
      lasted about an hour, focused on the candidates' professional knowledge involved
      in differential diagnosis and case management. Of 497 candidates examined between
      1994 and 1996, approximately 80% passed in their first attempt. However, about
      30% of the invited candidates did not appear for the exam. Characteristics of
      successful candidates were being young and being among the seniors with the least
      clinical experience. Most had specialized in internal medicine and had completed
      their observation period in a non-academic hospital. There they had received
      somewhat more attention than those who had been in academic hospitals.
      Significantly, the successful candidates were more proficient in Hebrew than the
      unsuccessful candidates, and reported no special problems during the observation
      period.

PMID- 10909541
TI  - [Trauma in Israeli Arab children--an epidemic that can be prevented].

PMID- 10909543
TI  - [Is humor in a medical article or lecture detrimental to its serious scientific
      value?].

PMID- 10909542
TI  - [Some medical aspects of Daniel Defoe and Robinson Crusoe].

PMID- 10909544
TI  - [Prevalence of pigmentary dispersion syndrome in Israel].
AB  - Pigmentary dispersion syndrome is a precursor of pigmentary glaucoma whose
      prevalence in the urban population of USA was found to be 2.45%. We evaluated its
      prevalence during ocular screening examinations among normal Israelis. We
      screened for excessive pigmentation on the corneal endothelium with the slit-lamp
      and determined in each patient best corrected visual acuity, intra-ocular
      pressure (after mydriasis), condition of the anterior segment, cup-disk ratio,
      posterior segment abnormalities and questioned about history of any ocular
      disease and family history of glaucoma. 374 patients (mean age 49 +/- 11) were
      examined on 10 consecutive days. In 5.9% excessive corneal endothelial
      pigmentation was found. Intra-ocular pressure (after mydriasis) averaged 15.52 +/
      1.93 mm Hg as compared to 14.73 +/- 2.04 among the rest of our study population,
      (p = 0.01). The prevalence of suspected pigmentary dispersion syndrome among
      young adults in Israelis is high.

PMID- 10909545
TI  - [Fibrosarcoma after silicone breast augmentation: is there a connection?].
AB  - We describe a 42-year-old woman in whom bilateral fibrosarcoma of the breast was
      diagnosed 15 years after bilateral breast augmentation with silicone implants. 3
      years prior to admission the implants were replaced and 2 years prior to
      admission mammography showed a nodule in the left breast which biopsy showed to
      be fibrosarcoma. The implants were removed from both breasts and she was given
      chemotherapy but later that year underwent bilateral mastectomy. Despite
      chemotherapy, as well as adjuvant radiotherapy, the disease progressed, with
      involvement of the lungs and the skin of the left hemithorax. She was admitted
      repeatedly for severe anemia caused by bleeding from the malignant skin lesions,
      and died less than 2 years after diagnosis of the disease. Not all reports in the
      literature find a significant connection between silicone implants and subsequent
      development of breast cancer, but there are reports that do connect them. Breast
      fibrosarcoma is not significantly more frequent after silicone augmentation, but
      still there is controversy as to whether there is a connection between silicone
      implants and breast malignancy. In the patient we present, the prolonged exposure
      to silicone may have been a predisposing factor for the development of bilateral
      fibrosarcoma, since other known risk factors for breast cancer were denied.

PMID- 10909546
TI  - [Characteristics of adults with emotional distress in Israel-- patterns of mental
      health services used].
AB  - We sought firsthand data on the extent of perceived mental health needs and on
      patterns of use of mental health services among Israelis aged 22 and over. The
      data are from a national survey conducted in 1995. A random sample of phone
      numbers from the telephone company's computerized listings yielded 1,395
      completed questionnaires (response rate, 81%). At some point in their lives, 27%
      had experienced emotional distress or mental health problems with which they had
      difficulty coping alone; 13.4% reported that they had such an experience during
      1995. According to multivariate analysis, those more likely to report mental
      health problems were women, those with a chronic disease, Russian immigrants,
      divorced or widowed adults, those with a low level of education, and members of
      the Clalit sick fund. 38% of those who had ever had emotional or mental health
      problems had asked for help. The proportion of those seeking help was high among
      respondents aged 35-55, Hebrew speakers (compared to speakers of Russian or
      Arabic), and city dwellers, and the rate was low among members of the Clalit sick
      fund. Of those who did seek help, 39% went to a psychologist or a psychiatrist,
      25% to their family doctor, 19% to a family member or friend, 7% to a social
      worker or social service agency, 6% to other medical personnel, and 4% to a
      psychiatric hospital. 30% turned for assistance to the private sector and 70% to
      the public sector. These findings have special significance in view of the
      impending reform of the mental health services. As mandated by the new National
      Health Insurance Law, mental health services are to be included in the basket of
      health services provided by the sick funds. The data can be of use in the
      management of sick funds and for physicians working in the community, as they
      prepare for this change. In addition, the data will be of aid to national policy
      makers in planning services suited to the needs of different population groups
      and to allocate resources more rationally.

PMID- 10909547
TI  - [What has happened to patient satisfaction with the care in general hospitals in
      the years from 1993-1995?].
AB  - Patient satisfaction with the hospitalization process is an important element in
      the measurement of quality of care. Information from a survey of patients'
      experiences could therefore help hospitals improve their service, and provide
      decision-makers with relevant information. We present the findings of a study of
      some 4,500 patients, aged 18+, released from hospitals in the fall of 1993 and of
      1995 from the wards of 9 acute care hospitals, psychiatric and geriatric wards
      excluded. Self-administered questionnaires were sent and returned by mail, with
      an overall response rate of 82%. Despite the many changes in Israel's health
      system in general and its hospital system in particular, and the social and
      demographic changes between those 2 periods, patient satisfaction remained
      constant. Of those discharged from medical or surgical wards, 70% were satisfied
      to a "great" or "ver great" extent with their hospital experience. There was
      improvement in most areas of hospitalization in the course of the 2 years. The
      greatest improvement was with regard to admission, nursing staff, hotel services,
      in patient satisfaction food and supplies. On the other hand there was
      deterioration in visiting conditions and hours. Satisfaction with physicians,
      nurses and hotel services had the strongest links with general satisfaction.

PMID- 10909548
TI  - [Primary dermatology--who is the gate keeper?].
AB  - For several years health funds in Israel have allowed patients to see
      dermatologists, gynecologists, orthopedic surgeons and ENT specialists without
      being referred by their primary care physician. There is heated debate about
      whether this practice is justified and if it is cost effective. Is it better
      medicine for the patient? What are the roles of the primary care physician and of
      the primary dermatologist in the care of skin diseases? What do patients want? We
      examined the practices of 4 dermatology clinics and discuss the issues involved.

PMID- 10909550
TI  - [Abdominal compartment syndrome].
AB  - Abdominal compartment syndrome refers to a complex of negative effects of intra
      abdominal hypertension. Its most common cause is complicated abdominal trauma.
      The syndrome includes mainly hemodynamic and respiratory manifestations but may
      involve other systems as well. It may present as a life-threatening emergency in
      the multi-trauma patient. Awareness of the syndrome may enable the surgeon to
      take preventive measures or to diagnose it earlier and to treat it effectively.
      We describe a 21-year old man who developed this syndrome after multiple gunshot
      wounds, with severe liver injury. After 2 operations the typical manifestations
      of the syndrome were diagnosed. He was re-operated to release intra-abdominal
      hypertension and then slowly recovered.

PMID- 10909549
TI  - [Perisacral angiosarcoma after radiotherapy for sigmoid carcinoma].
AB  - Secondary malignancy is a well-recognized complication of radiation therapy. The
      risk of postirradiation sarcoma in long-term follow-up is 0.03-0.8%. We report a
      case of radiation-induced perisacral angiosarcoma 6 years after pelvic
      irradiation for sigmoid cancer in a 77-year-old man. The tumor was diagnosed
      postmortem and was locally advanced and metastatic. He died 6 months after onset
      of symptoms. This case demonstrates the importance of long-term follow-up in
      those given radiotherapy.

PMID- 10909552
TI  - [Dyslexia after "one hundred years of solitude"].

PMID- 10909551
TI  - [Breast silicone implant and autoimmunity--coincidence or cause and effect
      relationship?].

PMID- 10909553
TI  - [Cardiac pacemakers and the cellular phone].

PMID- 10909555
TI  - [Quality assurance and quality improvement in the department of emergency
      medicine].

PMID- 10909554
TI  - [National survey: flexible bronchoscopy in Israel].

PMID- 10909557
TI  - [Breast milk--is it the best nutrition for preterm infants?].

PMID- 10909556
TI  - [Bone sarcomas: experience of an orthopedic oncology unit in the treatment of 180
      consecutive cases, 1988-1995 (Part II)].

PMID- 10909558
TI  - [Functional restoration of disability from chronic low back pain rehabilitation:
      medical approach].

PMID- 10909559
TI  - [Procreation--right or obligation?].

PMID- 10909560
TI  - [Prenatal diagnosis of Down's syndrome: prediction from maternal serum markers].

PMID- 10909561
TI  - [Birth defects in embryos from mothers with gestational diabetes-- etiology and
      new preventive approaches].

PMID- 10909562
TI  - [Topical optical beta-adrenergic antagonists and quinidine--a risky combination].

PMID- 10909563
TI  - [An algorithm for clearance of the cervical spine in patients after trauma].

PMID- 10909564
TI  - [Tick-borne encephalitis].